1. health and fitness
2. disease

The Primary Care
of Chronic Open
Angle Glaucoma
Report to the Royal College Ophthalmologists
Samya Riad – University College London Hospital
Supervisor: Richard Wormald – Moorfields Eye Hospital
Introduction
This report is directed to the primary care ophthalmologist. It is written in a way
so that s/he is knowledgeable about the clinical work that needs to be undertaken
in relation to glaucoma, the decisions that will have to be taken, mostly in
isolation, the latest in evidence based medicine and clinical guidelines pertaining
to glaucoma, the equipment needed to run a satisfactory service, the population
s/he will serve, models in glaucoma care running in other parts of the UK, the
views of her/his colleagues, his/her public health role in relation to glaucoma and
finally, research gaps to which s/he may wish to contribute.
The report is in three major divisions. The first consists of the clinical aspect of
the primary care of chronic open angle glaucoma and its evidence base. The
second includes policy aspects, most official documents and government
sponsored initiatives and the projected prevalence of chronic open angle glaucoma
in the different administrative areas of the UK. The third division contains models
of glaucoma delivery in the UK and the views of consultants and optometrists on
current trends in glaucoma care and future direction.
In this report, complete references are placed within the text and not at the end, as
traditional. This will allow the reader to know the source immediately. Also, the
major studies, the levels of evidence and the available clinical guidelines will be
presented at the beginning of the report in order to inform the reader of these
significant works from the start.
Abbreviations
The following abbreviations will be used in the text
AGIS
Advanced Glaucoma Intervention Study
ALT
Argon Laser Trabeculoplasty
CCT
Central Corneal Thickness
CIGTS
Collaborative Initial Glaucoma Treatment Study
CNTGS
Collaborative Normal Tension Glaucoma Study
COAG
Chronic Open Angle Glaucoma
CSLTC
Confocal Scanning Laser Tomography
EMGTS Early Manifest Glaucoma Treatment Study
FDT
Frequency Doubling Technology
GDX
Generic Digital Crosspoint
HFA
Humphrey Field Analyser
HRT
Heidelberg Retina Tomograph
HES
Hospital Eye Service
IOP
Intraocular Pressure
NFL
Nerve Fibre Layer
OAG
Open Angle Glaucoma
OH
Ocular Hypertension
OHTS
Ocular Hypertension Treatment Study
ON
Optic Nerve
PXE
Pseudoexfoliation
PDS
Pigment Dispersion Syndrome
POAG
Primary Open Angle Glaucoma
RCT
Randomised Controlled Trial
RNFL
Retinal Nerve Fibre Layer
VF
Visual Fields
Remit of the Primary Care Ophthalmologist
Unlike his/her hospital colleagues, who usually work with other ophthalmologists,
the primary care ophthalmologist will mostly work in isolation without the
advantage of an immediate discussion, exchange of clinical views or a second
opinion
He or she therefore should be trained to
1.
2.
3.
4.
5.
6.
Master instruments
Master clinical signs
Know of the conditions that he is expected to refer to HES
Know of the conditions that he is expected to discharge
Know of the conditions that is expected to follow up
Know of the conditions that he is expected to initiate treatment then refer
to HES
7. Know of the conditions that he is expected to initiate treatment then retain
in primary care
8. Know the risk factors for the condition
9. Know how to identify the risk factors for the condition
10. Appreciate the strength of the risk factor
11. Know and appreciate the risk factors for progression from ocular
hypertension to glaucoma
12. Know and appreciate the risk factors for progression of glaucoma in case
he/she is involved in a shared care scheme.
13. Select the appropriate equipment for his/her practice
14. Know of the performance and reliability of new equipment in order to
make wise decisions
15. Understand his/her local population
16. In the absence of a national screening programme for glaucoma, find ways
to enhance case finding the community where s/he works
17. To be update with current research and be able to participate
18. Train and direct his/her non medical team
19. Know of national models and trends for delivery of care in ophthalmology
and of nation
The Major Glaucoma Trials
The following is a list of the major glaucoma studies that will be referred to the in
this work as adapted from the European Glaucoma Society guidelines. Several
publications have been published under each study but only the name of the study
will be referred to the in the report.
I. The Ocular Hypertension Treatment Study (OHTS)
This is a multicentre, prospective study on patients with a normal ocular
examination, except for elevated IOP between 24 and 32 mmHg in one eye and
between 21 and 32 mmHg in the other eye. The purpose was to study differences
in conversion rates to POAG between the natural history (no treatment) and versus
treatment (IOP lowering treatment) in patients with elevated IOP (OH).
II. Collaborative Initial Glaucoma Treatment Study (CIGTS)
This is a randomised clinical trial on 607 patients with newly diagnosed open
angle glaucoma. Initial treatment was either medication or trabeculectomy ( with
or without 5- fluorouracil).
III. Collaborative Normal Tension Glaucoma Study (CNTGS)
This is a multicentre prospective randomized trial comparing treatment versus no
treatment in normal tension glaucoma. The primary outcome measure was disease
progression.
IV. The Advanced Glaucoma Intervention Study (AGIS)
This is a multicentre prospective randomised study on advanced open angle
glaucoma patients who suffer from glaucoma that cannot be controlled by
maximum tolerated medical therapy alone. The 591 patients of 35 to 81 years of
age (789 eyes) were randomised between two treatment sequences for further
interventions: argon laser trabeculoplasty → trabeculectomy → trabeculectomy
(ATT) and trabeculectomy → argon laser trabeculoplasty → trabeculectomy
(TAT). The second and third interventions were offered only after failure of the
first and second interventions, respectively.
V. Early Manifest Glaucoma Treatment Study (EMGTS)
This is prospective randomised trial of treatment vs no treatment to evaluate the
effectiveness of IOP reduction in early, previously untreated open angle
glaucoma. Secondary aims were to assess factors related to glaucoma progression
and to determine the natural history of the disease. During a population based
screening among 44,243 residents in Sweden, 316 eyes of 255 patients were
recruited.
The Major Epidemiological Surveys
There are seven major ophthalmic epidemiological studies to which there is
reference throughout the report. The following summary was adapted from the
work of the Eye Disease Prevalence Research Group*
Name of Study
Baltimore Eye
Survey
Barbados Study
Beaver Dam Eye
Study
Blue Mountains
Eye Study
Proyecto Vision
Evaluation
Research
Rotterdam Eye
Study
Vision
Impairment
Project
Location
Baltimore,
Maryland, USA
Barbados,
West Indies
Beaver Dam,
Wisconsin, USA
Sydney,
New South Wales,
Australia
Nogales and Tucson,
Arizona, USA
Year Conducted
1985 -1988
Number of Participants
5308
1988 -1992
4314
1988 - 1990
4585
1992 - 1994
3632
1999 - 2000
4773
Rotterdam,
The Netherlands
Melbourne,
Victoria, Australia
1990 - 1993
6774
1991 - 1998
4652
*Friedman DS, Wolfs RC, O'Colmain BJ, Klein BE, Taylor HR, West S, Leske
MC, Mitchell P, Congdon N, Kempen J; Eye Diseases Prevalence Research
Group.
Prevalence of open-angle glaucoma among adults in the United States.
Arch Ophthalmol. 2004 Apr;122(4):532-8.
The Clinical Guidelines
The following is a list of all clinical guidelines that were identified worldwide and
relating to chronic open angle glaucoma. They are all available on the website of
the respective organisations except for one guideline* which was published in a
peer reviewed journal. They are presented in descending order of their year of
publication.
1
2
3
4
5
6
7
8
9
Title
Organisation
Year
Primary Open Angle
Glaucoma (Initial
Evaluation)
Primary Open Angle
Glaucoma (Follow up
Evaluation)
Primary Open Angle
Glaucoma Suspect
(Initial and Follow up
Evaluation)
Primary Open Angle
Chronic Glaucoma,
Normal Tension
Glaucoma, and Ocular
Hypertension
(In German)
International Council of
Ophthalmology
2007
Country/
Region
Belgium
International Council of
Ophthalmology
2007
Belgium
International Council of
Ophthalmology
Not
Stated
Belgium
German Society of
Ophthalmology
2006
Germany
Primary Open Angle
Glaucoma – Preferred
Practice Pattern
Primary Open Angle
Glaucoma Suspect –
Preferred Practice
Pattern
Glaucoma
Guidelines for the
Management of Open
Angle Glaucoma and
Ocular Hypertension
Asia Pacific Glaucoma
Guidelines
American Academy of
Ophthalmology
2005
USA
American Academy of
Ophthalmology
2005
USA
Ministry of Health
The Royal College of
Ophthalmologists
2005
2004
Singapore
UK
SEAGIG (South East Asia
Glaucoma Interest Group)
with support of AOGS (Asia
2003 2004
Asia
Pacific
Region
10 Terminology and
Guidelines for
Glaucoma
11 The Finnish Evidence
Based Guideline for
Open Angle
Glaucoma*
12 Care of the Patient
with Open Angle
Glaucoma
Oceanic Glaucoma Society)
European Glaucoma Society
2003
Europe
Finnish Ophthalmologic
Society & The Finnish
Glaucoma Society
2003
Finland
American Optometric
Association
2002
USA
* Tuulonen A, Airaksinen PJ, Erola E, Forsman E, Friberg K, Kaila M, Klemetti
A, Mäkelä M, Oskala P, Puska P, Suoranta L, Teir H, Uusitalo H, Vainio-Jylhä E,
Vuori ML.
The Finnish evidence-based guideline for open-angle glaucoma. Acta Ophthalmol
Scand. 2003 Feb;81(1):3-18.
The following guidelines will be quoted repeatedly in the report and will be
referred to as follows
ICO – International Council of Ophthalmology (any of the three guidelines)
AAO – American Academy of Ophthalmology; Primary Open Angle Glaucoma –
Preferred Practice Pattern
Singapore - Singapore Ministry of Health; Glaucoma
RCOphth – The Royal College of Ophthalmologists; Guidelines for the
Management of Open Angle Glaucoma and Ocular Hypertension
Asia Pacific - South East Asia Glaucoma Interest Group; Asia Pacific Glaucoma
Guidelines
European Glaucoma Society – European Glaucoma Society; Terminology and
Guidelines for Glaucoma
Finland - Finnish Ophthalmologic Society & The Finnish Glaucoma Society; The
Finnish Evidence Based Guideline for Open Angle Glaucoma
AOA - American Optometric Association; Care of the Patient with Open Angle
Glaucoma
Levels of Evidence and Recommendations
In this report, the general principles of SIGN’s (Scottish Intercollegiate Guidelines
Network) levels of evidence and recommendations will be used. These have been
adapted to suit the circumstances under which this report was prepared. For the
level of evidence, every attempt was made to comply with the SIGN ratings but
sometimes, especially when a general review was summarised, the quality of the
studies it quoted and sometimes their design, was not known to the author. Also,
on some occasions, there were too few studies for the author to be able to evaluate
the evidence. This will be evident in the text. As for the recommendations,
SIGN’s recommendations are based on the level of evidence and should be
decided by a panel of experts. This was not available at this stage of the work, and
therefore it should be stressed that the recommendation included is only
approximate and based on discussions between the author and the supervisor and
should not be taken as the final recommendation but only an approximate
guideline.
The following are the levels of evidence and recommendations that have been
adapted from the SIGN ratings.
SIGN Levels of Evidence
Level 1 High quality or well conducted meta-analysis, systematic review of
RCTs, or RCTs with a very low risk of bias
Level 2 High quality systematic reviews of case control or cohort studies, or high
quality or well conducted case control or cohort studies with a low risk of
confounding, bias or chance and a high or moderate probability that the
relationship is causal.
Level 3 Non analytic studies example case reports or case series
Level 4 Expert opinion
SIGN Grades of Recommendation
A At least one high quality meta-analysis, systematic review or directly
applicable to the target population or a body of evidence consisting principally of
level 1 studies, directly applicable to the target population and demonstrating
overall consistency of results.
B A body of evidence including high quality level 2 studies, directly applicable
to the target population and showing overall consistency of results or extrapolated
evidence from medium or poor quality level 1 studies
C A body of evidence including medium quality level 2 studies, directly
applicable to the target population and showing overall consistency of results or
extrapolated evidence from high quality level 2 studies
D Evidence level 3 or 4 or extrapolated evidence from medium quality level 2
studies
Other Ratings
Four of the clinical guidelines that were presented previously have given levels of
evidence and recommendations to some of their statements. Each used different
ratings and no attempt will be made to compare them to each other or to SIGN
ratings. In the event of level of evidence or recommendation quoted from these
guidelines, the reader is advised to refer to the definitions given below. It should
be noted that whereas SIGN, Singapore and Finland base their recommendations
on the level of evidence, ICO and AAO base it on its importance to the care
process.
ICO Ratings
Levels of Evidence: I: Strong, II: Substantial but lacks some of I, III: consensus
of expert opinion in absence of evidence for I & II
Grades of recommendation: A: Most important, B: Moderately important, C:
Relevant but not critical
AAO Ratings
Levels of Evidence
Level I includes evidence obtained from at least one properly conducted, welldesigned, randomized, controlled trial. It could include meta-analyses of
randomized controlled trials.
Level II includes evidence obtained from the following:

Well-designed controlled trials without randomization

Well-designed cohort or case-control analytic studies, preferably from
more than one center
Multiple-time series with or without the intervention

Level III includes evidence obtained from one of the following:

Descriptive studies

Case reports
Reports of expert committees/organizations (e.g., PPP panel consensus
with peer review)

Grades of Recommendation
These recommendations are based on “importance to the care process” and their
ratings represent care that the panel thought would improve the quality of the
patient’s care in a meaningful way. The recommendations of importance are
divided into three levels.
Level A, defined as most important
Level B, defined as moderately important
Level C, defined as relevant but not critical
Singapore Ratings
Levels of Evidence
Ia Evidence obtained from meta-analysis of randomised controlled trials.
Ib Evidence obtained from at least one randomised controlled trial.
IIa Evidence obtained from at least one well-designed controlled study without
randomisation.
IIb Evidence obtained from at least one other type of well-designed
quasi-experimental study.
III Evidence obtained from well-designed non-experimental descriptive
studies, such as comparative studies, correlation studies and case studies.
IV Evidence obtained from expert committee reports or opinions and/or
clinical experiences of respected authorities.
Grades of Recommendation
A (evidence levels Ia, Ib)
Requires at least one randomised controlled trial as part of the body of literature of
overall good quality and consistency addressing the specific recommendation.
B (evidence levels IIa, IIb, III)
Requires availability of well conducted clinical studies but no randomised clinical
trials on the topic of recommendation
C (evidence level IV)
Requires evidence obtained from expert committee reports or opinions and/or
clinical experiences of respected authorities. Indicates absence of directly
applicable clinical
studies of good quality
GPP (good practice points)
Recommended best practice based on the clinical experience of the guideline
development group.
Finland Ratings
Depending on the quality and size of original studies, the strength of each
statement is graded from A to D. Level A represents ‘strong research based
evidence’, that is multiple, relevant, high-quality studies with homogenous results
(e.g. two or more randomized, controlled trials), or a systematic review with
clearly positive results. Level B represents ‘moderate evidence’ (e.g. one
randomized, controlled trial, or multiple adequate studies). Level C represents
‘limited research-based evidence’ (e.g. open, controlled, prospective studies).
Level D represents ‘no evidence’ (e.g. retrospective studies, or the consensus
reached by the group in the absence of good quality evidence). Recommendations
for action are then formulated based on the studies of highest quality.
Division One
The Evidence Based Content of the
Primary Care of Chronic Open Angle
Glaucoma







Method
Definition
Health Education
Screening
Prevalence
Risk Factors
Detection
Method
1. The elements and content of the primary care of chronic open angle glaucoma
were compiled, based on the following definition and on current clinical
practice
“Ophthalmic
primary care is the provision of first contact care for all ophthalmic
conditions and the follow up, preventive, and rehabilitative care of selected
ophthalmic conditions. It can be delivered in a variety of settings and by a diverse
workforce, but in strict, efficient, and timely coordination, to attain the best
clinical outcome possible for the patient. A service is designated as ophthalmic
primary care, only if appropriately integrated with the patient’s main primary care
provider, in order to ensure continuity, longitudinality, and comprehensiveness in
the overall care of the patient. The primary care ophthalmic service itself should
be accessible, equitable, knowledgeable, responsive, and efficient. In these aims, it
is supported by the population sciences which identify the medical and service
needs of the population served.”*
2. Each section starts by the reason why it is included in the report which is also
an explanation of its relevance to primary care.
3. A key question is asked on each topic, which is then discussed using the
following method
a. If an evidence synthesis report of good quality is available, its results
are summarised and the subject is not taken further.
b. If there is no evidence synthesis report, and a general review is
available, then it is summarised.
c. If the evidence synthesis report or the general review are found to be
lacking on certain points, then the relevant publications are added and
summarised.
d. If there are no reports or reviews, then the relevant significant literature
is summarised.
e. If relevant, the evidence level is given at the end of the summary of the
publication and the grade of recommendation is given at the end.
f. The reference of each of the clinical guidelines to the topic is included
either if it adds to the discussion or to demonstrate the significance of
the topic. The extent of the inclusion of the guidelines differs from one
section to the other as necessary and as will be evident in the report.
*Riad SF, Dart JKG, Cooling RJ.
Primary care and ophthalmology in the UK.
Br J Ophthalmol (2003); 87:493-499.
Definitions
Why is this section included in the report?
A precise definition of chronic open angle glaucoma and its related conditions is
needed for the ophthalmologist who will work in a primary care setting and whose
remit will partly be to decide on which cases to refer to the hospital eye service
and which to retain in primary care, based on a reliable definition. Ophthalmic
primary care, as an embryonic ophthalmic subspecialty, will need to develop its
own identity and its practitioners will need to see their duties based on a scientific
definition rather than a set of guidelines. A precise definition will also define the
boundaries of primary care thus precluding it from encroaching on patient care
that needs to be delivered in the hospital eye service.
Background
The lack of consistency on how glaucoma is defined in clinical research has been
long recognised1,2. Krause and Burton3 in 20033 argued that the absence of an
agreed detailed case definition for POAG that can be applied in clinical practice
results in considerable uncertainty about the diagnosis of this condition. Clinical
definitions of chronic open angle glaucoma and its related conditions have been
included in clinical guidelines compiled worldwide. As will be seen, there are no
fundamental differences between these definitions, because unlike definitions
utilised in clinical research, they do not go to operational detail. Some may
include more parameters than others, e.g. the reference to outflow facility by the
Royal College of Ophthalmologists and the inclusion of the rapidly progressive
form in the Finnish guidelines, but in general, there is an overall consensus of
definition.
Definitions of Chronic Open Angle Glaucoma and Related Conditions in
Clinical Guidelines
AAO 2005
Primary Open Angle Glaucoma
Primary open-angle glaucoma is a progressive, chronic optic neuropathy in adults
where intraocular pressure (IOP) and other currently unknown factors contribute
to damage and in which, in the absence of other identifiable causes, there is a
characteristic acquired atrophy of the optic nerve and loss of retinal ganglion cells
and their axons. This is associated with an anterior chamber angle that is open by
gonioscopic appearance.
The Glaucoma Suspect
A glaucoma suspect is an individual with clinical findings and/or a constellation
of risk factors that indicate an increased likelihood of developing POAG. The
clinical findings that define a glaucoma suspect are characterized by one or more
of the following in an individual with open anterior-chamber angles by
gonioscopy: 1. appearance of the optic disc or retinal nerve fibre layer that is
suspicious for glaucomatous damage, 2. a visual field suspicious for glaucomatous
damage and 3. consistently elevated intraocular pressure (IOP) associated with
normal appearance of the optic disc and retinal nerve fibre layer and with normal
visual field test results. The following have been implicated as important risk
factors in the development of glaucomatous optic nerve damage: 1. elevated IOP
measurement, 2. Older age, 3. family history of glaucoma, 4. African or
Hispanic/Latino descent and 5. thinner central corneal thickness. This definition
excludes known secondary causes for potential open-angle glaucoma, such as
pseudoexfoliation, pigment dispersion and traumatic angle recession
Singapore 2005
Primary Open Angle Glaucoma
Glaucoma is an optic neuropathy with characteristic changes in the optic nerve
head and visual field. Raised intraocular pressure (IOP) is the main risk factor for
the development and progression of this
disease.
Normal Tension Glaucoma
Normal tension glaucoma (NTG) is an important subtype of POAG, in which the
IOPs are consistently within the statistically normal population range.
.RCOphth 2004
Ocular Hypertension
Ocular hypertension (OHT) is a term reserved for eyes in which the intraocular
pressure (IOP) lies above the normal population range, the optic nerve and visual
field show no signs of glaucomatous damage, and there is no ocular co-morbidity.
Excluded from this definition are eyes with raised IOP from demonstrable causes
such as pseudoexfoliation and pigment dispersion syndrome.
Primary Open Angle Glaucoma
Primary open angle glaucoma (POAG) is a chronic progressive condition with
characteristic changes at the optic disc (glaucomatous excavation), where it is
usually possible to identify reduced visual function related to the disc changes. In
most patients, the IOP is above the normal range (i.e. over 21 mmHg) at some
time of the day, usually being highest in the morning. In addition, there is a
gonioscopically open angle indistinguishable from normal and, in those eyes with
elevated IOP, a reduced facility of outflow.
Normal tension glaucoma
Apart from the finding of an IOP that does not exceed 21 mmHg, this form of
open angle glaucoma may be indistinguishable from its higher pressure variant.
European Glaucoma Society 2003
Ocular Hypertension
(Compiled Definition)
A condition of unknown aetiology and unknown pathomechanism where the peak
IOP is more than 21 mm Hg without treatment (diurnal curve), the visual fields
are normal, the optic disc and retinal nerve fibre layer are normal and gonioscopy
shows an open anterior chamber angle. There is no history or signs of other eye
disease or steroid use and there are no other risk factors.
Primary Open Angle Glaucomas
The open angle glaucomas are chronic progressive optic neuropathies, that have in
common characteristic morphological changes at the optic nerve head and retinal
nerve fibre layer in the absence of other ocular disease or congenital anomalies.
Progressive retinal ganglion cells death and visual field loss are associated with
these changes. The relative risk for POAG rises continuously with the level of the
intraocular pressure (IOP), and there is no evidence of a threshold IOP for the
onset of the condition. It is presumed that risk factors other than IOP have a
relatively greater importance if there is glaucomatous optic neuropathy at the
lower (statistically ‘normal’) pressure levels. POAG had been arbitrarily divided
into High Pressure and Normal Pressure disease to reflect this, even though they
may represent a spectrum of optic neuropathies variably sensitive to the IOP.
Asia Pacific 2003 -2004
Primary Open Angle Glaucoma
Chronic progressive optic neuropathy with characteristic changes with
characteristic changes in the optic nerve head and/or visual field in the absence of
secondary causes
Ocular Hypertension
Intraocular pressure more than two standard deviations above the population mean
with open angles and no evidence of glaucomatous optic neuropathy or visual
field loss (with normal central corneal thickness).
Normal Pressure Glaucoma
Characteristic glaucomatous optic neuropathy in the presence of statistically
normal intraocular pressure
Finland 2003
Glaucoma is a progressive neuropathy of the optic nerve with typical structural
and functional abnormalities in the optic disc, retinal nerve fibre layer and visual
field. In the majority of patients, the glaucomatous abnormalities progress slowly
over the years. In a minority of patients, the disease may, however, lead to serious
optic nerve damage within just a few months.
AOA 2002
Primary Open Angle Glaucoma, Ocular Hypertension and Normal Tension
Glaucoma
POAG is a chronic, progressive disease that most often presents with
characteristic optic nerve (ON) damage, nerve fibre layer (NFL) defects, and
subsequent visual field (VF) loss. OAG occurs primarily in adults and is generally
bilateral, but not always symmetrical, in its presentation. The majority of persons
with POAG have elevated intraocular pressure (IOP). Although 21 mm Hg is
considered the upper limit of statistically normal IOP, at least one-sixth of patients
with POAG have IOP levels below 21 mm Hg, which is considered statistically
normal in the 95th percentile range. Moreover, some whose IOP levels are
statistically abnormal (>21 mm Hg) have no evidence of ON damage or loss of
vision function, a condition known as ocular hypertension (OH). OAG in which
the IOP is typically below a certain level, typically 21 mm Hg, is known as low
tension or normal tension glaucoma (NTG).
The Primary Care Perspective
The above definitions are more useful in a hospital setting where a clear cut
designation of the patient under a classification scheme is not as important for
decision making. However, for the primary care ophthalmologist, in a community
or a referral refinement setting, who is looking for an operational definition, in
order to make referral decisions, a precise definition is important. For example,
the Royal College of Ophthalmologists specifies that for the diagnosis of ocular
hypertension, there should be no associated ocular morbidity. This may give rise
to a situation where the primary care ophthalmologist is faced with a patient who
fulfils all the criteria for a diagnosis of ocular hypertension, but has early lens
changes, senile macular degeneration or an old corneal scar. Definitions for
ophthalmic primary care will require attention to details like levels of IOP, the
evidence based significance of the different risk factors, the interpretation of the
optic disc characteristics and visual field changes in the detection phase of the
disease. As will be seen later, such evidence is not always available, which
constitutes a challenge in the development of such guidelines.
References
1. Bathija R, Gupta N, Zangwill L, et al. Changing definition of glaucoma.
J Glaucoma 1998;7:165–9
2. Foster PJ, Buhrmann R, Quigley HA, et al. The definition and
classification of glaucoma in prevalence surveys. Br J Ophthalmol
2002;86:238–42
3. Kroese M, Burton H. Primary open angle glaucoma. The need for a consensus
case definition. J Epidemiol Community Health 2003;57:752–754
Health Education
Why is this section included in this report?
Health education is included in this report because, in the absence of a national
screening programme for glaucoma, education of subjects at risk of developing
glaucoma is a significant pathway for the identification of glaucoma cases and
glaucoma suspects at the primary care level. If persons at risk are made aware of
their position and advised to seek regular examination with the optometrist, then
this will contribute to the identification of patients at an early stage of the disease.
Health education targets the population hence its inclusion in primary care.
Key Questions
Question 1 – Is there evidence that the population in the UK or a comparable
society is aware about glaucoma and its risk factors?
Evidence Synthesis – There is no evidence synthesis report on this question.
The Literature
Michielutte R, Diseker RA, Stafford CL, Carr P.
Knowledge of diabetes and glaucoma in a rural North Carolina community.
J Community Health. 1984 Summer;9(4):269-84.
This is a telephone survey of residents in one rural community to determine
knowledge, attitudes, and practices concerning diabetes and glaucoma. Results of
the survey indicated that the level of knowledge for both diabetes and glaucoma is
particularly low with respect to identification of high-risk groups and symptoms;
the lowest levels of knowledge were observed in the youngest and oldest
respondents, males, the unmarried, and those with low levels of educational
attainment.
Level of Evidence - 3
Livingston PM, Lee SE, De Paola C, Carson CA, Guest CS, Taylor HR.
Knowledge of glaucoma, and its relationship to self-care practices, in a population
sample.
Aust N Z J Ophthalmol. 1995 Feb;23(1):37-41.
A cluster sample of 1711 persons of Melbourne population 40 years and older was
interviewed. Seventy per cent of the sample had heard of glaucoma. However,
only 22% provided a description that demonstrated a reasonable understanding of
the disease. A lack of awareness and knowledge of glaucoma appeared to be
negatively related to self-care practices.
Level of Evidence - 3
Attebo K, Mitchell P, Cumming R, Smith W.
Knowledge and beliefs about common eye diseases.
Aust N Z J Ophthalmol. 1997 Nov;25(4):283-7.
A population based survey of an urban Australian population aged 49 years or
older to ascertain knowledge of common causes of blindness. Awareness of
glaucoma was 93%, however among those who were aware of glaucoma only
29% showed some knowledge of glaucoma. Those who were aware and had some
knowledge of eye disease accessed eye care services more frequently.
Level of Evidence - 3
Pfeiffer N, Krieglstein GK, Wellek S.
Knowledge about glaucoma in the unselected population: a German survey.
J Glaucoma. 2002 Oct;11(5):458-63.
A total of 2,742 persons aged 14 to 93 years, representative of the German
populations, were interviewed face to face to determine their knowledge about
nature, occurrence and possible risk factors of glaucoma. Fifty one percent had
knowledge of the term glaucoma when asked about eye disease. Seventy five
percent had heard about glaucoma when asked specifically about it. Twenty-five
percent of respondents assumed that all people are equally at risk, and 21%
thought that relatives of glaucoma patients carry a higher risk. Age was
recognized as a risk factor by 12% (over 40 years), 32% (over 60 years) and 4%
(over 80 years)
Level of Evidence - 3
Mansouri K, Orgul S, Meier-Gibbons F, Mermoud A.
Awareness about glaucoma and related eye health attitudes in Switzerland: a
survey of the general public.
Ophthalmologica. 2006;220(2):101-8.
A cluster random sample of 502 individuals between the age of 35 and 70,
representing urban and rural populations was interviewed by telephone to assess
their level of awareness about glaucoma. In total, 76% of respondents did not have
any (or any correct) association with the term 'glaucoma'. Only 24.7% of the
interviewees could describe glaucoma as an eye condition. Awareness of
glaucoma was independent of age, gender, educational status, and household
income.
Level of Evidence - 3
Noertjojo K, Maberley D, Bassett K, Courtright P.
Awareness of eye diseases and risk factors: identifying needs for health education
and promotion in Canada.
Can J Ophthalmol. 2006 Oct ;41(5):617-23.
This is a cross-sectional survey of 882 adult patients presenting to using selfadministered questionnaires of patients presenting to 33 family practitioners'
offices in British Columbia. Overall, 41.2% reported familiarity with glaucoma.
Women were 1.6 times more likely than men to report familiarity with glaucoma.
Respondents with university education were 1.8 times more likely to report
familiarity with glaucoma than were those with no family education. Canadians
with European descent were 2.9 times more likely to report familiarity with
glaucoma than were non-European descent Canadians. Family history was
recognized by only 23% of respondents. Women, those of European ancestry and
those with university education were more likely to recognise family history as a
risk factor for glaucoma. Medications were recognised as a risk factor by 4.4% of
respondents.
Level of Evidence - 3
Question 2 - Is there evidence that subjects at risk of developing glaucoma in the
UK or a comparable society are aware of the need for regular eye examination?
Evidence Synthesis – There is no evidence synthesis report on this question.
The Literature
Eke T, Reddy MA, Karwatowski WS.
Glaucoma awareness and screening uptake in relatives of people with glaucoma.
Eye. 1999 Oct;13 ( Pt 5):647-9
Seventy first degree relatives of glaucoma patients in Leicester, aged over 40
years, were identified and returned a questionnaire on glaucoma awareness and
screening uptake. Only 53% thought they were at increased lifetime risk of
developing glaucoma.
Level of Evidence - 3
Landers JA, Goldberg I, Graham SL.
Factors affecting awareness and knowledge of glaucoma among patients
presenting to an urban emergency department.
Clin Experiment Ophthalmol. 2002 Apr;30(2):104-9.
A total of 240 patients, with no previous history of glaucoma or ocular
hypertension, presenting to an urban hospital emergency department in Sydney,
Australia were surveyed with a brief questionnaire to assess their knowledge of
glaucoma. Data was collected about their gender, age, family history of glaucoma
and presence of systemic hypertension, diabetes, Raynaud's phenomenon,
migraines and myopia. Women (Odds ratio 2.3), people who were 40 years or
older (Odds ratio 2.2) and those who were aware of a family history of glaucoma
(Odds ratio 15.7) knew significantly more about the disease than others, while
people with other risk factors did not demonstrate significantly greater knowledge.
Level of Evidence - 2
Question 3 – Is there evidence that subjects who are aware of being at risk of
developing glaucoma in the UK or a comparable society are attending for
screening?
Evidence synthesis – There is no evidence synthesis report on this question.
The Literature
In the study by Eke et al, 1999, above, uptake of regular, free glaucoma screening
at least every 2 years was 57% among offspring and 30% among siblings. The
responses of patients' siblings and patients' offspring were compared and revealed
that perceived lifetime glaucoma risk was similar in the two groups, but the
(older) siblings had a significantly lower awareness of the free screening service
and attended for screening less frequently. Uptake of regular, free glaucoma
screening at least every 2 years was 57% among offspring and 30% among
siblings.
Level of Evidence - 3
Question 4 – Is there evidence of an intervention in the UK or a comparable
society which has been successful in increasing awareness of glaucoma risk or the
need for seeking regular eye examination by those at risk?
Evidence synthesis – There is no evidence synthesis report on this question.
The Literature
Baker H, Murdoch IE.
Can a public health package on glaucoma reach its target population?
Eye. 2004 May;18(5):478-82.
A pilot study was conducted to assess how successful an advertisement in a local
newspaper and an interview on local radio about glaucoma are at reaching their
target population. The target population were residents aged 45 years and above in
Southall in the West of London and the Isle of Wight. In Southall, a convenience
sample was taken from local temples and the high street, the majority of which
was of Indian ethnicity. In the Isle of White, the sample was taken from the main
town centre and it was 100% Caucasian. Using a pre and post intervention
questionnaire, it was found that the proportion who had heard of glaucoma
increased from 27 % before the intervention to 40% after the intervention in
Southall and from 71% to 79% in the Isle of White. On the Isle of White, females
were more knowledgeable and responded more positively to the intervention. This
differed in Southall where males tended to be the positive responders. The
increase in the proportion of those who had heard of the disease was attributed to
both the advert and interview in Southall but to the newspaper advertisement
alone on the Isle of White, as only 3% of respondents reported hearing the radio
interview. In a complete logistic regression model with ‘heard of glaucoma’ as the
outcome, adjusting for age, gender and intervention, the only important factor was
the intervention.
Level of Evidence - 2
Screening
Why is this section included in the report?
Screening tests are population based hence the inclusion of screening in the
primary care of chronic open angle glaucoma. The term ‘glaucoma screening’ is
sometimes used in the hospital setting to refer to the examination of patients
referred from the community in order to categorise them into normal individuals,
glaucoma suspects or glaucoma patients. Obviously, these are the patients who
were suspected to have glaucoma in the community via opportunistic case finding
or suggestive symptoms. True screening will examine all individuals in the
community who are at risk of developing glaucoma and not only those who have
been referred to the hospital eye service.
As screening is a major primary care subject, it will be presented in a different
format. It will inform the reader of the definition, measures, criteria and basics of
screening, the situation in the United Kingdom, the international scenario and
finally opinions of authors who have written on the subject.
The Definition of Screening
The UK National Screening Committee defines screening as a public health
service in which members of a defined population, who do not necessarily
perceive that they are at risk of, or are already affected by a disease or its
complications, are asked a question or offered a test, to identify those individuals
who are more likely to be helped than harmed by further tests or treatment to
reduce the risk of a disease or its complications1.
The Measures of Screening
Wormald2 explained the measures of the process of screening as follows. The
validity of a test is its ability to differentiate correctly between those who have
the disease and those who do not. Two kinds of error, false-positive and false negative, may occur, both of which are important in a screening programme..
Sensitivity (detection rate) is the proportion of persons with the disease that the
test correctly identifies. Thus the sensitivity of a test is a measure of its ability to
detect disease in those who are affected. Specificity (true-negative rate) is the
proportion of persons who are disease-free that the test identifies as normal.
Thus the specificity of a test is a measure of its ability to identify correctly those
who are disease-free. The relation between sensitivity and specificity is
important. Increasing the sensitivity of a test will usually be at the expense of
specificity, and vice versa. The computation of these test parameters depends
upon the existence of a gold standard that can determine the truth with regard to
the disease status of the participants. This can be problematic in some situations,
for example when it is hard to categorise individuals clearly as diseased and nondiseased, or when the case definition is imprecise. This is particularly true for
glaucoma. In nature, few diseases demonstrate a clear step from being diseasefree to being affected. Usually there is a continuum between health and disease,
particularly for chronic or degenerative disease. Thus, an arbitrary judgment
based on practical considerations must be made in order to decide when the
transition from health to disease has occurred. Positive predictive value (PPV)
is the probability of being disease-positive if the test is positive. This is an
important parameter because it reveals the amount of work the screening test will
generate at the referral centres and the number of persons who will be
unnecessarily referred for further examination. It is determined by the falsepositive rate but also influenced by the prevalence of the disease. It can also be
described as the conditional probability of being disease-positive if the test is
positive. This can be expressed as: PPV = (sensitivity x prevalence) divided by
the probability of a positive test. It is the combined probability of the test
detecting a case when among known cases (i,e. the sensitivity) and the probability of the individual being a case in the target population (the prevalence)
divided by the overall probability of a test being positive in the population. Thus
even when the test sensitivity is high, if the prevalence is low so also will be the
PPV. Negative predictive value (NPV) is the probability of being diseasenegative if the test is negative. This is relevant to the concerns of screened
individuals, and influences the degree of assurance that the screened negative
person can assume when the test is negative. Like PPV, it is prevalencedependent. When the prevalence is low, the NPV will tend to be high, even
though the test may be quite insensitive. Yield is the number of persons screened
to detect one case and is also dependent on prevalence of the disease in the
population. Yield can be extended to include cost per yield and, further, cost per
yield that are then successfully treated. Prevalence is the proportion of true
cases in the population and is an important consideration in any screening
programme because of its effect on PPV; but it is also a measure of the public
health importance of the disease. A reasonably precise estimate of the prevalence
of a disease is required before screening can be implemented. The reliability of
a test is a product of the variation in the test results, whereas validity deals with
the ability of the test to distinguish normal from abnormal. A reliable test gives
consistent results when repeated on the same individual. It depends on the
variation inherent in the test itself (sometimes termed reproducibility), which
may be random or biological, and that introduced by the observer who conducts
the test, which may be both random or systematic (intra- (within) and inter (between) observer variation).The sources of variation can be the subject or the
instrument. Coverage is the proportion of the population at risk who are
screened during anyone trawl. Acceptability of the screening test is of
importance. An unpleasant, painful or invasive test will deter response. The
target population must be properly informed about the nature and purpose of the
screening test so that they can clearly understand that there is a real benefit to be
derived from attending the screening examination. Access to the screening site
must be optimal. Long and costly travel to the site will deter attendance. Ideally,
screening should be available within the community of the target population,
outside the hospital setting (which is associated with fear and disease), and
preferably in the primary care setting where individuals are used to having
contact with healthcare services. Feedback, explanation and reassurance about
the outcome of the examination are essential for all individuals so that the word
spreads in the community that attending the screen is a positive experience.
The Basics of Screening for Glaucoma
Quigley3reviewed the subject and highlighted the following screening elements
that need to be taken into account in a glaucoma screening programme
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Parameters used for screening differ in different populations
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The instruments used must be reliable
The personnel who will perform the tests must be experienced
New perimetry tests for screening that were found promising when
evaluated on experienced patients in the clinic where found to have lower
specificity and sensitivity when used on populations with no past
experience
New perimetry tests for screening may be ignored because they were
tested against a gold standard that is less effective in detecting new cases.
The true cases identified by the new perimeter may be classified as false
positives.
Glaucoma for screening purposes needs to defined with rigour
Some persons will be screened positive because they have other eye
disease These usually represent an increased yield because major eye
disease has been detected
Cost should refer to the cost of the finished test including purchase price,
servicing, training cost, useful life, number of units needed for the
programme and associated costs e.g. printer and paper.
The test should be fast
The test should be acceptable to the individuals being screened in terms of
not being painful, frightening, frustrating or embarrassing.
The predictive power of the test used in screening should be high
The test should not be affected by the different types of populations being
screened
Tests that include pupil dilatation are time consuming, costly and carry the
risk of precipitating acute closed angle glaucoma
Tests that include dark adaptation are time consuming
The instruments should be preferably portable
The test should have well characterised output measures, which are easy to
interpret and are not subjective
Simple judgement should be required for the person being tested if the test
includes a subjective element
Training of the examiner is substantially simpler for tests with automated
sequences than for those that are manually operated.
The test should be appropriate for the stage of glaucoma that needs to be
detected
Immediate results are more useful
Screening Tests for Glaucoma
These have been discussed by Wormald2. The three tests necessary for the
diagnosis of glaucoma, namely an lOP measurement, an optic disk examination
and a visual field assessment, all perform poorly as single tests, with both low
sensitivity and PPV. The combination of lOP and disk assessment only marginally
improves the validity: and the current view of the American Academy of
Ophthalmology is that all three tests should be performed routinely in the
comprehensive eye examination. Despite it being clearly shown in 1966 by
Hollows and Graham that the IOP is inadequate as a screening index,
opportunistic testing for glaucoma in many circumstances relies on pressure
measurement. Despite this inadequacy, it remains true that after age, a raised IOP
is the single most significant risk factor for glaucoma. When found, a high IOP
needs treating and the risk of developing glaucoma (if not already present) should
be carefully assessed. Disk changes in glaucoma can be extremely subtle and are
the domain of experienced glaucoma specialists who can detect potentially
pathognomonic change. These changes are too subtle for use in screening, and
agreement between specialists in recognizing them changes has been shown to be
poor. The presence of a definite groove or defect in the nerve fibre layer, which
can be sometimes seen with direct or indirect ophthalmoscopy (and better with a
red-free filter), is a strong indicator of glaucoma and is very unlikely to be a falsepositive finding, even though it may precede the appearance of a definite
abnormality of visual function. But the absence of a visible defect does not
exclude glaucoma. Detection of an NFL defect requires good clarity of the optical
media and usually a dilated pupil. To visualise an NFL groove easily may also
require that the nerve fibre damage is focal and that the rest of the NFL is thick,
young and healthy. None of these conditions make this technique likely to be
suitable for screening in the community, although technological developments in
this area may change this. The reliable demonstration of an abnormal visual function in screening for glaucoma is probably the best hope for the development of a
screening tool. Visual function is traditionally assessed in glaucoma by plotting
the visual field, and numerous methods now exist for the execution of this test. A
major problem arises from the fluctuation in retinal sensitivity which is a normal
feature of visual function. This variation is accentuated in glaucoma patients. The
process of identifying the threshold of perception is an arduous task which
requires many repetitions. These and other reasons are enough to exclude
threshold testing as a possible screening tool, but suprathreshold techniques have
been widely tested and show promise. The principle of this strategy is to reduce
the false positive rate by looking only for marked focal reductions in retinal
sensitivity. The price is some loss of sensitivity to the detection of early defects.
Screening for Glaucoma in the United Kingdom and Worldwide
Population screening for glaucoma has been rejected in the UK, USA, Quebec,
Finland and Singapore. These are the countries that have recorded their experience
or views, but it is also not known of any countries worldwide that have a national
screening programme for glaucoma4.
Screening for Glaucoma in the United Kingdom
In the United Kingdom, the body responsible for screening is the UK National
Screening Committee (NSC) which advises Ministers, the devolved national
Assemblies and the Scottish Parliament on all aspects of screening policy5. The
NSC assesses proposed new screening programmes against a set of internationally
recognised criteria covering the condition, the test, the treatment options and
effectiveness and acceptability of the screening programme6.
In 2001, Spry and Sparrow evaluated open angle glaucoma against these criteria
and found that some but not all criteria were met7. As a result, screening for open
angle glaucoma was not offered by NSC.
Currently another review commissioned by the Health Technology Assessment
Programme of the Department of Health is being carried out by Dr Jennifer Burr,
a clinical epidemiologist at the University of Aberdeen8. This review will include
1) a systematic review of screening and diagnostic strategies to determine the
accuracy, reliability and acceptability of alternative strategies in different
population groups in a UK setting, 2) an update of Cochrane reviews to assess
short-term effects of alternative management strategies for glaucoma 3) a
statistical modelling to extrapolate the effects of IOP changes on later visual
impairment and 4) a systematic review of economic evaluations, followed by
economic modelling of cost-effectiveness and cost-utility, if possible, of
alternative approaches to screening. The forecast publication date is October 2007
Screening for Glaucoma in the United States of America
In 2005, the US Preventive Services Task Force (USPSTF) found insufficient
evidence to recommend for or against screening adults for glaucoma9. In 2007, the
American Academy of Ophthalmology wrote to AHRQ (Agency for Healthcare
Research and Quality), which sponsors the development of systematic evidence
reviews, requesting a re-evaluation of the recommendations because of new
evidence regarding screening for and treatment of glaucoma not available at the
time of the USPSTF report and because of significant concerns regarding the
scope and applicability of the USPSTF recommendation10. AHRQ responded that
they would not re-evaluate glaucoma screening on a more rapid schedule and that
they would clarify in the future that the scope of the report is not glaucoma
screening by primary care clinicians, which is implied by the current title of the
report. The Academy had proposed a screening benefit under Medicare where the
ophthalmologist would be performing the screening in their office with
appropriate staffing and supervision11.
Screening for Glaucoma in Quebec, Canada
In 1995, the Quebec Agency for Health Services and Technology Assessment
(AETMIS) stated that a formal screening program for primary open angle
glaucoma (POAG) could not be recommended for the province of Quebec, owing
to “a high degree of uncertainty and because of the high cost such a program
would entail.”12 An article in response to this decision was published in 2005 in
the Canadian Journal of Ophthalmology to evaluate the possibility of instituting a
POAG screening programme in light of recent advances in the diagnosis and
treatment of glaucoma. Currently in Canada, screening for POAG (detecting
glaucoma and ocular hypertension) generally occurs during routine clinical patient
visits, without
being part of a formal POAG screening protocol.12
Screening for Glaucoma in Finland
The Finnish evidence based guideline for open angle glaucoma does not
recommend mass screening in the public sector due to insufficient evidence for its
cost effectiveness. Instead, it recommends that the Finnish people, at their own
initiative, have an ocular examination performed by an ophthalmologist, from the
age of 40-45 to 60 every 5 years and every 3 years for those above 6013.
Screening for Glaucoma in Singapore
The glaucoma guidelines by the Ministry of Health and the National Committee
on Ophthalmology do not recommend routine population screening for glaucoma.
However, high risk individuals may be considered as target populations for case
detection programmes14.
The Evidence Synthesis
I The Agency of Healthcare Research and Quality15
The following eight key questions were assessed for evidence by the Agency for
Healthcare Research and Quality. They include screening for ocular hypertension
and primary open angle glaucoma.
Key Question 1.
Is there new evidence that screening for open angle glaucoma reduces severe
visual impairment?
Results: There are no studies assessing the screening and treatment of open-angle
glaucoma in a population setting.
Key Question 2
Is there new evidence that feasible screening tests are accurate and reliable in
detecting increased intraocular pressure or open-angle glaucoma?
Results:
1. Using current methods, optic nerve assessment is neither a practical nor reliable
tool for population screening.
2. At the present time, perimetry has a limited role in population screening
programmes because of the expense of equipment, the amount of time necessary
for
testing (up to 10-20 minutes per eye), and the relative lack of portability of most
instruments.
3. Henson Visual Field Analyse is currently used in population screening and FDT
is a promising instrument due to its portability, ease of administration and short
time required for testing. Population studies are needed on these to instruments to
determine their true performance as population tools.
Key Question 3
Is there new evidence that treating increased intraocular pressure reduces
the incidence of primary open angle glaucoma?
The Ocular Hypertension Treatment Study (OHTS) has shown that over the
duration of the study, the hazard ratio for progression of ocular hypertension to
POAG in all treated vs. untreated participants was 0.40 and was 0.54 in treated vs.
untreated blacks.
Key Question 4
Is there new evidence that treating increased intraocular pressure reduces
severe visual impairments?
There were no studies that assessed the treatment of ocular hypertension using
delay of progression to severe visual impairment as an endpoint.
Key Question 5
Is there new evidence that treating open angle glaucoma with drugs, laser,
and/or surgery reduces severe visual impairment?
The Early Manifest Glaucoma Trial (EMGT) was a randomized clinical trial
comparing treatment with no treatment in 255 individuals with early POAG.
One hundred and twenty-nine participants were randomized to treatment with
argon laser trabeculoplasty (ALT) and topical beta-blocker eye drops. The
remaining 126 control participants received no treatment. At 48 months, the
minimum planned follow up, 30% of treated subjects reached a progression
endpoint vs. 49% of control subjects.
In the Collaborative Normal-Tension Glaucoma Study (CNTGS), 145 eyes of 145
individuals with manifestations of POAG, but without recorded IOP elevation
(>24 mm Hg) on repeated testing, were randomized to receive treatment with
medications or surgery to lower IOP by 30%, or to receive no treatment. A total of
35 progression endpoints were observed. Seven of 61 eyes (12%) in the treated
group reached progression endpoints compared with 28 of 79 (35%) in the
untreated group.
In the CNTGS study, 23 of 66 treated eyes (35%) developed loss of visual acuity
due to cataracts, compared with 11 of 79 eyes in the control group (14%) The
highest incidence of cataracts (16 of 33) occurred in the surgically treated eyes.
The rate of cataract formation in untreated eyes was lower than surgically treated
eyes, but was not significantly different from medically treated eyes.
The first CNTGS paper indicates that IOP does play a pathogenic role in normaltension glaucoma. However, the results of the second paper31 do not indicate
whether treating IOP would effectively reduce glaucoma progression in patients
with NTG. In the EMGT study, secondary analyses show that increased IOP is a
significant risk factor for progression. This indicates that treatment directed at
lowering IOP is definitely beneficial for eyes with increased IOP, but of uncertain
benefit in eyes with normal IOP.
The Collaborative Initial Glaucoma Treatment Study (CIGTS), in which
participants were randomized to treatment with surgical trabeculectomy or to a
stepwise medication regimen, concluded that both medical and surgical treatment
result in similar VF outcomes. They caution, however, that 4 to 5 years of followup in a chronic disease is not adequate to draw treatment conclusions.
The Glaucoma Laser Treatment (GLT) study compared initial treatment with ALT
to a stepwise regimen of topical and systemic ocular hypotensive medications.
There were no observed differences between treatment groups in either visual
acuity or visual field changes over 24 months.
Key Question 6
Is there new evidence that screening results in adverse effects? Is screening
acceptable to patients?
There were no studies addressing the harms or acceptability of screening for
ocular hypertension or POAG.
Key Question 7
Is there new evidence that treatment of increased intraocular pressure and/or
open-angle glaucoma results in adverse effects?
In the OHTS, ocular symptoms occurred in 57% of treated patients and 47% of
control subjects. Other symptoms, such as darkening of the eyelids or eyelash
growth, were reported in 23% of treated patients vs.18% of control subjects.
The CIGTS trial reported intraoperative and postoperative complication for
surgical trabeculectomy in 525 participants.
II The Cochrane Collaboration
A Cochrane review16 was undertaken in 2006 to determine the impact of screening
for OAG compared with opportunistic case findings or current referral practices
on the prevalence of and the degree of optic nerve damage due to OAG in
screened and unscreened populations. The authors pointed out that the challenge
of screening for OAG is to detect the disease at a stage where it is sufficiently
present to be accurately identified in those individuals who are at risk of going
blind in their lifetime if left untreated. Detecting very early disease may not
necessarily be the most effective and efficient way to screen if resources are to be
focused on those at risk of blindness. Attempting to detect the condition in its very
early stages is likely to generate more false positive errors and identify numerous
people whose sight is not threatened. Ultimately, the effectiveness of screening as
a means of preventing the adverse effects of a disease in a population can be
demonstrated only by randomised trials of screening where individuals or clusters
of individuals are randomised to be screened, or not, thereby testing the
hypothesis that screened individuals will have a lower risk of suffering the effects
of the disease than the unscreened individuals. The authors concluded that on the
basis of current evidence, population-based screening for chronic OAG cannot be
recommended, although much can be done to improve awareness and encourage
at risk individuals to seek testing.
III Centre for Reviews and Dissemination
Two records on the cost effectiveness of screening were compiled by CRD
commissioned reviewers according to a set of guidelines developed in
collaboration with a group of leading health economists.
The first record is for a study17 to determine the cost-effectiveness of glaucoma
screening under 12 different scenarios. In scenario 1, screening is done every 3
years using both funduscopy and tonometry for people aged 40-79 years, the
participation rate and compliance rate is 75% and treatment efficacy is 50%. In
scenarios 2 and 3, all assumptions are the same as scenario 1, except that
screening is carried out at 1 and 5 year intervals, respectively. Scenarios 4 to 9
vary the participation rate (60%, 75% and 90%), compliance rate (60%, 75% and
90%), and efficacy of treatment (30%, 50% and 70%). In scenario 10, the
screening age is restricted to 65-79 years. Scenarios 11 and 12 assume that
tonometry is the only screen used, and vary the ages from 40-79 years, and 65-79
years, respectively. The authors concluded that there is no proof that treatment of
glaucoma would prevent blindness. Even when treatment efficacy is assumed to
be as high as 50%, glaucoma screening programmes were not shown to be
competitive with regard to cost-effectiveness.
The second record is for a study18 to assess the cost-effectiveness of different
modes of screening/case-finding for glaucoma defined in terms of various
combinations of three main tests (ophthalmoscopy, tonometry and perimetry) with
associated referral criteria (relatively lax or relatively severe). No specific mode of
screening was regarded as a comparator. The authors concluded that "glaucoma
screening of people over age 40 years could be justifiable, provided that it is
worth more than about $850 (£548 at 1995 values) to detect a new case. The
modes of glaucoma testing which can provide the best balance between sensitivity
and cost are those which use ophthalmoscopy and tonometry routinely on patients
over the age of about 40 years, together with perimetry either routinely or on
glaucoma high risk groups. Screening is most likely to be economic when
conducted (as systematised "case-finding") in conjunction with overall eye
examinations, thus minimising the costs of ophthalmoscopy and overheads. The
cost per glaucoma detected can be as low as $850 at 1995 prices, with sensitivity
for those tested of >/= 80%. If the real worth of detecting a new case is considered
likely to exceed this, there is reason to promote and improve potentially economic
systems of detection.
References
1. http://www.nsc.nhs.uk/whatscreening/whatscreen_ind.htm
2. Wormald P. Screening in Ophthalmology. In, The Epidemiology of Eye
Diseases. GJ Johnson, DC Minassian, RA Weale, SK West (Eds). Arnold,
London, 2003. pp 88-101.
3. Quigley HA. Current and future approaches to glaucoma screening.
J Glaucoma. 1998 Jun;7(3):210-20.
4. Wormald RP, Rauf A. Glaucoma screening. J Med Screen. 1995;2(2):109-14..
5. http://www.nsc.nhs.uk/uk_nsc/uk_nsc_ind.htm
6. http://www.nsc.nhs.uk/pdfs/criteria.pdf
7. Spry PGD; Sparrow JM. An Evaluation of Open Angle Glaucoma against the
NSC Criteria for Screening Viability, Effectiveness and Appropriateness
NSC, September 2001
8. http://www.hta.ac.uk/ProjectData/1_project_record_notpublished.asp?PjtId=1446
9. http://www.ahrq.gov/clinic/uspstf05/glaucoma/glaucrs.htm
10.http://www.aao.org/education/statements/loader.cfm?url=/commonspot/security/ge
tfile.cfm&PageID=37601
11. (Personal Communication with AAO on June 12, 2007).
12. Harasymowycz P, Kamdeu Fansi A, Papamatheakis D. Screening for primary
open-angle glaucoma in the developed world: are we there yet? Can J
Ophthalmol. 2005 Aug;40(4):477-86.
13. Tuulonen A, Airaksinen PJ, Erola E, Forsman E, Friberg K, Kaila M, Klemetti
A, Mäkelä M, Oskala P, Puska P, Suoranta L, Teir H, Uusitalo H, Vainio-Jylhä E,
Vuori ML. The Finnish evidence-based guideline for open-angle glaucoma. Acta
Ophthalmol Scand. 2003 Feb;81(1):3-18.
14. Ministry of Health. Glaucoma. MOH Clinical Practice Guidelines 3/2005.
Singapore 2005.
15. Fleming C, Whitlock E, Beil T, Smit B. Primary Care Screening for Ocular
Hypertension and Primary Open-Angle Glaucoma: Evidence Synthesis. Agency
for Healthcare Research and Quality. Evidence Synthesis no.34.
16. Hatt S, Wormald R, Burr J. Screening for prevention of optic nerve damage
due to chronic open angle glaucoma. Cochrane Database Syst Rev. 2006 Oct
18;(4):CD006129
17. Boivin J F, McGregor M, Archer C. Cost effectiveness of screening for
primary open angle glaucoma. Journal of Medical Screening, 1996; 3(3): 15463.16.
18. Tuck M W, Crick R P. The cost-effectiveness of various modes of screening
for primary open angle glaucoma. Ophthalmic Epidemiology, 1997; 4(1): 3-17
,
,
Prevalence
Why is Prevalence included in the report?
The primary care ophthalmologist should be aware of the prevalence of glaucoma
in the community that he serves for the following reasons: 1) for planning, 2) for
research, 3) for making informed decisions about capacity, and 4) for making a
case for his services and his needed workforce.
Background
There is sufficient evidence in the literature that the prevalence of glaucoma
differs according to race and according to age. Therefore, in order to estimate the
prevalence of chronic open angle glaucoma with optimum accuracy in a defined
population, the prevalence rates within the different subgroups and the distribution
of these subgroups within the population need to be known. In another part of this
report, these calculations for the populations of the different primary care trusts
will be presented. In this section, the results of prevalence surveys will be
reviewed.
There are prevalence surveys from many parts of the world. For the purpose of
this work, we will only include results from prevalence surveys of races that are
present in significant numbers in the United Kingdom namely
1.
2.
3.
4.
5.
6.
7.
Whites
Blacks
Mixed Races
Indians
Pakistani
Bangladeshi
Chinese
Key Question
What is the prevalence of glaucoma in white, black, mixed black, Indians,
Pakistanis, Bangladeshis and Chinese races in age groups above 40 years old?
Evidence Synthesis
There are two meta-analyses on the prevalence of glaucoma in the different races.
Friedman DS, Wolfs RC, O'Colmain BJ, Klein BE, Taylor HR, West S, Leske
MC, Mitchell P, Congdon N, Kempen J; Eye Diseases Prevalence Research
Group.
Prevalence of open-angle glaucoma among adults in the United States.
Arch Ophthalmol. 2004 Apr;122(4):532-8.
Rudnicka AR, Mt-Isa S, Owen CG, Cook DG, Ashby D
Variations in primary open-angle glaucoma prevalence by age, gender, and race: a
Bayesian meta-analysis.
Invest Ophthalmol Vis Sci. 2006 Oct; 47(10):4254-61
The first study was conducted by an international research group and calculated
prevalence for the purpose of estimating the prevalence and distribution of open
angle glaucoma in the United States. They therefore concentrated on eight studies
that were found useful for this purpose.
The second study is more recent and was conducted in the UK (St George’s and
Queen Mary’s, University of London). Forty-six published observational studies
of OAG prevalence (103,567 participants with 2509 cases of OAG) were
included.
The results of the two studied were close and the results of the second study will
be presented in this work.
Age Range in Years Predicted Prevalence of OAG (95% Credible Interval)
White
Black
Asian
30 - 39
1.8 (1.2 – 2.7)
0.4 (0.3 – 0.6)
40 - 49
0.4 (0.3 – 0.6)
2.9 (1.9 – 4.4)
0.6 (0.4 – 1.0)
50 - 59
0.8 (0.5 – 1.2)
4.6 (3.1 – 6.8)
1.0 (0.6 – 1.6)
60 - 69
1.6 (1.1 – 2.5.)
7.2 (4.9 – 10.6)
1.6 (1.0 – 2.4)
70 - 79
3.3 (2.2 – 4.9)
11.2 (7.6 – 16.1)
2.5 (1.6 – 3.8)
80 - 89
6.6 (4.4 – 9.7)
16.9 (11.7 – 23.8) 3.8 (2.3 – 5.9)
90 - 95
10.8 (7.2 – 15.8) 22.5 (15.7 – 31.2)
The pooled random effects prevalence estimates of OAG for those above 40 years
of age is 1.4% (95% CI, 1.0% – 2.0%) in Asian populations, 4.2% in black
populations (95% CI, 3.1% - 5.8%) and 2.1% (95%CI, 1.6% - 2.7%) in white
populations.
It will be noticed that the authors have placed all Asians in one category. No
reason was given for this, but the following tables, compiled by the author of this
report, show that overall, the prevalence rates and their confidence intervals are
comparable between the different populations of the Indian subcontinent and
between these populations and Chinese populations.
Prevalence of Glaucoma in Chinese Populations
Country
Number of Sample
Participants Type
Thailand
701
Cross sectional over 50
Monglia
942
All over 40
Singapore 1232
Prevalence
of
POAG%
2.3% (95
CI, 1.3 3.7)
0.5
Disproportionate stratified
2.4% (95
clustered random sample 40 CI, 1.6 to 79
3.2)
Reference
Bourne et
al 1
Foster et
al 2
Foster et
al 3
Prevalence of Glaucoma in Indian Populations
Country
Number of Sample
Participants Type
Reference
Southern
India
934
Dandona et al4
South India 972
Bangladesh 2347
Southern
India
5150
South India 3934
Prevalence
of
POAG%
Cross
2.56%
sectional
(95% CI,
over 40
1.22 -3.91)
Cluster
0.41%
sample 30 (95% CI,
to 60
0.008 –
0.81) .
Multistage 2.1%(95%
stratified
CI, 1.5-2.9)
cluster
sample
over 40
Cross
1.7% (95%
sectional
CI, 1.3 –
clustered
2.1)
over 40
Non
1.62%
random
(95% CI,
sample
1.42 –
over 40
1.82)
Jacob et al 5
Rahman et al 6
Ramakrishnan
et al 7
Vijaya et al 8
References
1. Bourne RR, Sukudom P, Foster PJ, Tantisevi V, Jitapunkul S, Lee PS, Johnson
GJ, Rojanapongpun P. Prevalence of glaucoma in Thailand: a population based
survey in Rom Klao District, Bangkok. Br J Ophthalmol. 2003 Sep;87(9):106974.
2. Foster PJ, Baasanhu J, Alsbirk PH, Munkhbayar D, Uranchimeg D, Johnson
GJ.
Foster et al Glaucoma in Mongolia. A population-based survey in Hovsgol
province, northern Mongolia. Arch Ophthalmol. 1996 Oct;114(10):1235-41.
3. Foster PJ, Oen FT, Machin D, Ng TP, Devereux JG, Johnson GJ, Khaw PT,
Seah SK. The prevalence of glaucoma in Chinese residents of Singapore: a crosssectional population survey of the Tanjong Pagar district. Arch Ophthalmol. 2000
Aug;118(8):1105-11.
4. Dandona L, Dandona R, Srinivas M, Mandal P, John RK, McCarty CA, Rao
GN. Open-angle glaucoma in an urban population in southern India: the Andhra
Pradesh eye disease study. Ophthalmology. 2000 Sep;107(9):1702-9.
5. Jacob A, Thomas R, Koshi SP, Braganza A, Muliyil J. Prevalence of primary
glaucoma in an urban south Indian population. Indian J Ophthalmol. 1998
Jun;46(2):81-6.
6. Rahman MM, Rahman N, Foster PJ, Haque Z, Zaman AU, Dineen B, Johnson
GJ. The prevalence of glaucoma in Bangladesh: a population based survey in
Dhaka division. Br J Ophthalmol. 2004 Dec;88(12):1493-7.
7. Ramakrishnan R, Nirmalan PK, Krishnadas R, Thulasiraj RD, Tielsch JM, Katz
J, Friedman DS, Robin AL. Glaucoma in a rural population of southern India: the
Aravind comprehensive eye survey. Ophthalmology. 2003 Aug;110(8):1484-90.
Erratum in: Ophthalmology. 2004 Feb;111(2):331.
8. Vijaya L, George R, Baskaran M, Arvind H, Raju P, Ramesh SV,
Kumaramanickavel G, McCarty C. Prevalence of Primary Open-angle Glaucoma
in an Urban South Indian Population and Comparison with a Rural Population The
Chennai Glaucoma Study. Ophthalmology. 2007 Jul 28
Risk Factors
Why is this section included in the report?
Risk factors are important in suspecting and diagnosing glaucoma in primary care.
The primary care ophthalmologist will need to know these factors in order to
recognise patients who may have glaucoma. The primary care ophthalmologist,
who will follow up ocular hypertension, needs to know which patients are more at
risk of developing glaucoma. Finally, the risk factors for the progression of
glaucoma are important for determining which patients could be followed up
safely in primary care.
A note on the clinical guidelines and risk factors for glaucoma
Available clinical guidelines have varied in their approach to the subject of risk
factors for glaucoma. The AAO, for example, explicitly states that risk factors are
discussed as part of the background section, which does not include
recommendations, but is designed to provide the rationale for the
recommendations that are presented in the care process section. The Finland
guidelines provide recommendations, whilst the AAO guidelines give
comprehensive reviews on many factors. In this section therefore, reference will
be made only to guidelines with a distinct contribution to the discussion.
In this section, the following categories of risk factors will be examined
1. Risk factors for the development of chronic open angle glaucoma
2. Risk factors for the progression of ocular hypertension to chronic open
angle glaucoma
3. Risk factors for the progression of chronic open angle glaucoma
I. Risk factors for the development of chronic open angle glaucoma
Key Question – Is there evidence that any of the following characteristics or
conditions is a risk factor for the development of glaucoma?
This will be presented according to the classification by Boland and Quigley
Boland MV, Quigley HA.
Risk factors and open-angle glaucoma: classification and application.
J Glaucoma. 2007 Jun-Jul;16(4):406-18
An evidence level is given for each publication. At the end of each risk factor, a
conclusion of knowledge up to date is given. This is followed by a level of
recommendation which denotes the strength of the conclusion in terms of
available evidence. A summary table based on the level of recommendation is
given at the end of the discussion.
1 Age
Evidence Synthesis
Rudnicka AR, Mt-Isa S, Owen CG, Cook DG, Ashby D
Variations in primary open-angle glaucoma prevalence by age, gender, and race: a
Bayesian meta-analysis.
Invest Ophthalmol Vis Sci. 2006 Oct; 47(10):4254-61
Results of the above meta-analysis showed that in white populations, the odds
ratio of OAG per decade is 2.05, whereas in black populations, the odds ratio is
1.6 per decade and in Asian populations, it is 1.57 per decade. These findings
indicate that proportional increase in prevalence of OAG with age was highest in
white populations. In 40 to 49 year olds, the prevalence of OAG in black
populations was approximately 7 times higher than the prevalence in white
populations, whereas by age 80 to 89 years, the prevalence was approximately 2.5
times higher. The prevalence in Asian populations was similar to the prevalence in
white populations at ages 40 to 69; thereafter, it was relatively higher in white
populations.
OR per decade; whites 2.05, blacks 1.6, Asians 1.57
Level of Evidence – 1
Conclusion – Increased age is a risk factor for the development of POAG
especially among white populations.
Recommendation – A
State of the Individual
2. Gender
Evidence Synthesis
Rudnicka et al above stated that the controversy around whether a gender
difference exists in the prevalence of POAG may be explained by lack of power
with insufficient numbers of OAG cases within individual studies. In their metaanalysis, published estimates by gender were available for 25 studies with 61267
participants and 1355 case of OAG. Overall, the prevalence of OAG in men was
1.37 times that in women after adjusting for age, racial group, publication year
and survey methods. On stratification by racial group, the odds ratio for OAG in
men compared with women was 1.46 in white populations, 1.27 in black
populations and 1.36 in Asian populations.
OR men to women; white 1.46, black, 1.27, 1.36
Level of Evidence – 1
Conclusion – Male gender is a risk factor for the development of POAG in
white, black and Asian populations
Recommendation - A
3. Ethnicity
Evidence Synthesis
As discussed in the section on prevalence and age, the meta-analysis by Rudnicka
et al has shown that at all ages, black populations have the highest prevalence
estimates of OAG.
The pooled random effects prevalence estimates of OAG is 1.4% (95% CI, 1.0% –
2.0%) in Asian populations, 4.2% in black populations (95% CI, 3.1% - 5.8%) and
2.1% (95%CI, 1.6% - 2.7%) in white populations.
Prevalence; white 2.1, black 4.2, Asian 1.4
Level of Evidence – 1
The Literature on Blacks
Wormald RP, Basauri E, Wright LA, Evans JR.
The African Caribbean Eye Survey: risk factors for glaucoma in a sample of
African Caribbean people living in London.
Eye. 1994;8 ( Pt 3):315-20.
This is a study of a cross sectional voluntary sample of Afro Caribbean people
living in the London Borough of Haringey to estimate the prevalence and risk
factors of chronic glaucoma. Skin colour was graded as light, medium or dark.
The prevalence of glaucoma in the light skin was 1.7%, in the medium skin 3.5%
and 4.5% in the dark skin (p=0.38). Dark skin colour was significant as a risk
factor only when the outcome was definite glaucoma plus glaucoma suspects plus
ocular hypertension. African origin as a risk factor had the strongest odds ratio
(OR) after age for the development of definite glaucoma. Africans accounted for
only 16% of the sample and were younger than the West Indians. They came
mainly from Nigeria and Ghana. The authors concluded that data from this study
is insufficient to throw more light on this observation and should probably be
interpreted with caution.
Level of Evidence - 3
Murdoch IE, Cousens SN, Babalola OE, Yang YF, Abiose A, Jones BR.
Glaucoma prevalence may not be uniformly high in all 'black' populations.
Afr J Med Med Sci. 2001 Dec;30(4):337-9.
The authors examined a population of Hausa/Fulani individuals in rural Northen
Nigeria. The overall prevalence of open angle glaucoma in this population was
1.02% (0.12 to 3.64, 95% confidence interval) in individuals 45 years of age and
older which is lower than the prevalence rates reported for other "black"
populations. The authors mentioned that the low prevalence of glaucoma detected
in this African population may be, to some extent, a reflection of the age structure
of the population studied or methodological differences in ophthalmic
examinations performed. It is also possible that the prevalence of glaucoma varies
considerably between "black" populations due to genetic heterogeneity or the
effect of some unidentified environmental exposure. The authors concluded that
the use of the simple description of populations as 'black' (or 'white'), which
focuses on a commonality, tends to obscure the potential heterogeneity within and
between populations and thus may be unhelpful in some circumstances.
Level of Evidence - 2
Racette L, Wilson MR, Zangwill LM, Weinreb RN, Sample PA.
Primary open-angle glaucoma in blacks: a review.
Surv Ophthalmol. 2003 May-Jun;48(3):295-313.
In this review, the authors compared the prevalence of glaucoma in five different
studies on blacks. There was variation in the prevalence estimates of the different
studies but the authors pointed out that this variability may be due to differences
in the definitions, criteria and/or testing methods used to define, diagnose and
classify POAG.
Level of Evidence - 3
Conclusion – At all ages, black populations have the highest prevalence
estimates of OAG, compared to other races. There may be a significant
variation in prevalence between different black populations but this is not
definite.
Recommendation - B
4. Family History
Key Questions
Evidence Synthesis – There is no evidence synthesis report on this question
The Guidelines - AOA
Studies have suggested that 13 -25 percent of patients with glaucoma may have
family histories positive for the disease. In close relatives of persons with POAG,
the prevalence is 3-6 times that of the general public, and the incidence of the
disease in first-degree relatives is 3−5 times that found in the general population.
The 22 percent lifetime risk for glaucoma found in relatives of patients with
glaucoma is almost 10 times that of controls. The risk may be greater in siblings
than in parents or children. A family history of glaucoma puts a person with OH at
greater risk of developing the disease. Ocular characteristics associated with
glaucoma, including IOP and the cup-to-disc ratio, have been associated with
moderate familial risk.
The Literature
Tielsch JM, Katz J, Sommer A, Quigley HA, Javitt JC.
Family history and risk of primary open angle glaucoma. The Baltimore Eye
Survey
Arch Ophthalmol. 1994 Jan;112(1):69-73
This study is based on a population prevalence survey of 5308 black and white
residents of east Baltimore, USA, which identified 161 cases of primary open
angle glaucoma among subjects who were 40 years of age or older. Family history
was ascertained by interview and included all first-degree relatives (parents,
siblings, and children). Results showed a higher risk of glaucoma in siblings than
in parents or children (odd ratios: 3.69, 2.17, and 1.12, respectively) of known
glaucoma patients.
OR; siblings 3.69, parents 2.17, children 1.12
Level of Evidence – 2
Wolfs RC, Klaver CC, Ramrattan RS, van Duijn CM, Hofman A, de Jong PT
Genetic risk of primary open-angle glaucoma. Population-based familial
aggregation study
Arch Ophthalmol. 1998 Dec;116(12):1640-5
In this population based Rotterdam study, Wolfs et al, found that the prevalence of
primary open angle glaucoma was 10.4% in siblings of patients, 1.1% in offspring
of patients, 0.7% in siblings of controls, and 0% in offspring of controls. Life-time
risk of primary open angle glaucoma was 22.0% in relatives of patients vs. 2.3%
in relatives of controls. Enlarged cup-disc ratio, not intraocular pressure, was the
earliest and most prominent feature of familial aggregation.
Prevalence; siblings patients 10.4%, offspring patients 1.1%, 0.7% siblings
controls, offspring controls 0%
Level of Evidence – 2
Leske MC, Nemesure B, He Q, Wu SY, Fielding Hejtmancik J, Hennis A
Patterns of open-angle glaucoma in the Barbados Family Study.
Ophthalmology. 2001 Jun;108(6):1015-22
This is a case control study in a black population. Leske et al examined 207
families of probands which included 1056 family members. They found that 10%
of the probands had two or more relatives affected with OAG and 29% had one
relative with OAG. They also compared sibling with and without OAG and found
that the affected siblings were significantly older than those without the disease
and more often were male. Siblings with OAG had higher IOP, lower diastolic
blood pressure–IOP differences, and more myopia than unaffected siblings.
Level of Evidence - 2
Sung VC, Koppens JM, Vernon SA, Pawson P, Rubinstein M, King AJ, Tattersall
CL
Longitudinal glaucoma screening for siblings of patients with primary open angle
glaucoma: the Nottingham Family Glaucoma Screening Study.
Br J Ophthalmol. 2006 Jan;90(1):59-63
In this study, a group of siblings of OAG probands underwent initial and follow
up standardised ophthalmic examinations with a mean interval of 7 years between
both examinations. In the first examination, 271 siblings from 156 probands were
examined. Of these, 32 (11.8%) were classified as definite glaucoma and 15
(5.5%) as suspects. In the second examination, 157 of the 224 "normal" siblings
from the initial examination were examined and 11 (7%) were classified as
definite glaucoma and 30 (19.1%) as suspects. The authors compared these results
to those of a Bedford Survey conducted in the 1980s on 101 individuals with a
positive family history of glaucoma. The study reported only a 3% incidence of
definite glaucoma after 10–12 years of follow up. The authors of the Nottingham
study attributed this lower incidence, compared to their findings, to the fact that
only 17 of the Bedford survey subjects were siblings and the others were mostly
children of probands and by necessity of much younger age.
Level of Evidence – 3
Wiggs JL
Genetic Etiologies of Glaucoma
Arch Ophthalmol. 2007;125:30-37
Glaucoma may be inherited as mendelian-dominant or mendelian recessive traits
(usually early-onset forms of the disease), or may exhibit a heritable susceptibility
consistent with complex trait inheritance (typically adult-onset forms of the
disease).
Genetic approaches have helped define the underlying molecular events
responsible for some mendelian forms of the disease and have identified the
chromosome locations of genes that are likely to contribute to common complex
forms. Adult-onset glaucoma often occurs in multiple family members (familial
aggregation) but does not usually follow a clear mendelian inheritance pattern,
suggesting that inherited risk factors can result in a susceptibility to the disease
but alone are not necessarily causative. Multiple risk factors and/or environmental
factors may be responsible for this disease in older individuals. Defects in MYOC
coding for myocilin are found in 3% to 5% of patients with adult-onset POAG.
Certain MYOC mutations are more commonly found in older-onset patients than
in early-onset patients. In particular, the nonsense mutation Q368X, which results
in a truncated polypeptide, is more frequently found in patients with adult onset
POAG than in patients with early-onset POAG.
Conclusion – There is level 2 evidence that siblings of patients with POAG
have a higher risk of developing the disease than parents or children.
Affected siblings are significantly older than those without the disease and
more often male. Siblings with OAG have higher IOP, lower diastolic blood
pressure–IOP differences, and more myopia than unaffected siblings.
Recommendation - C
Ocular Anatomy and Physiology
5. Increased Intraocular Pressure
Evidence Synthesis – There is no evidence synthesis report on this question
The Guidelines - AOA
Intraocular pressure has a strong, direct relationship with the prevalence and longterm risk for glaucoma. For persons with IOP above 21 mm Hg, the risk of
developing glaucoma is 16 times the risk for persons with IOP below 16 mm Hg.
Moreover, the percentage of eyes developing visual field defects after 5 years is
percent for those with IOP over 20 mm Hg, compared with 1.5 percent of eyes
with IOP below 20 mm Hg. Even in NTG, it was found that the higher the
pressure, the greater the risk. Asymmetric levels of IOP in individual pairs of eyes
correlate risk for optic nerve damage. Long-term studies have consistently shown
that a large percentage of persons with statistically elevated IOP (>21 mm Hg) do
not develop glaucoma, while many persons with glaucoma have IOP well within
the statistically normal range. Population-based studies have demonstrated that
one-tenth or fewer of those with elevated IOP suffer visual field loss when
monitored over several years. The incidence of glaucoma among persons with
ocular hypertension is at most 1 percent per year. One-third to one-half of persons
with glaucoma have IOP at or below 20 mm Hg at initial diagnosis.
The Literature
Boland and Quigley mentioned that nearly every study has shown that the level of
IOP is a risk factor for OAG incidence, prevalence and progression. Both the three
clinical trials that followed the natural history of a recruited population and the
three population based incidence studies from Melbourne, Barbados and South
India identified higher IOP as a risk factor for the development of glaucoma. In
the South India study, the diurnal fluctuation in IOP was found to be an
independent risk factor as well.
Level of Evidence – 2
Le A, Mukesh BN, McCarty CA, Taylor HR
Risk factors associated with the incidence of open-angle glaucoma: the visual
impairment project
Invest Ophthalmol Vis Sci. 2003 Sep;44(9):3783-9
This is a population based study which included 3271 participants recruited from
nine urban areas through cluster random sampling and examined at baseline and
five years follow up. For increased intraocular pressure, the authors calculated, by
multivariate analysis, a relative risk (RR) for the development of at least possible
and at least probable glaucoma (grading based on the judgment of the examiner
and not clinical criteria), of RR 1.1 (95% CI, 1.03–1.2) and RR 1.1(95% CI, 1.04–
1.2) respectively.
RR; at least possible glaucoma 1.1, at least probable glaucoma 1.1
Level of Evidence – 2
Conclusion – There is level 2 evidence that there is an increased risk for the
development of POAG with increased levels of intraocular pressure.
Recommendation - C
6. Exfoliation Syndrome
Evidence Synthesis – There is no evidence synthesis report on this question.
The Guidelines – AOA
The prevalence of pseudoexfoliation syndrome varies widely throughout the
world ranging from about 1.6 to 2.3 percent in persons over age 50 in the United
States. The prevalence of PEX with subsequent pseudoexfoliation glaucoma
increases with age, and these conditions most commonly occur between the ages
of 60 and PEX is 2−3
times more common in women than in men and its prevalence in African
Americans is much lower than in Caucasians. Through family studies, several
putative sites on chromosome 2 are being investigated for genetic mutations
related to PEX.
PEX is a definite risk factor for OH and OAG. On initial screening, OH is found
in 22−30 percent of individuals with PEX.OH develops in about 10 percent of
persons who had PEX and normal IOP at initial diagnosis. The cumulative
probability of developing OH is 5.3 percent in 5 years and 15.4 percent in 10
years. The prevalence of PEX in a glaucoma population ranges from 1.6 to 28
percent in the United States. Thirty to sixty percent of individuals with PEX have
been reported to develop OAG.
The Literature
Mitchell P, Wang JJ, Hourihan F.
The relationship between glaucoma and pseudoexfoliation: the Blue Mountains
Eye Study.
Arch Ophthalmol. 1999 Oct; 117(10):1319-24.
This is a cross-sectional study of 3654 people aged 49 to 97 years identified
subjects with PEX during slitlamp examination. Glaucomatous damage was
present in 14.2% of eyes with PEX compared with 1.7% of eyes without PEX
(age- and sex-adjusted odds ratio (OR), 5.0; 95% CI, 2.6-9.6). This was almost
unchanged (OR, 4.8) after adjustment for glaucoma risk factors and was also
relatively unaffected by IOP adjustment (OR, 3.7; 95% CI, 1.8-7.6). For subjects
with PEX, the relationship with glaucoma persisted, but was weaker (OR, 2.3;
95% CI, 1.0-5.0) in the multivariate model. However, the population attributable
risk from PEX was only 2.7%.
OR glaucomatous damage in eyes with PEX to eyes without PEX after
adjustment is 4.8
Level of Evidence - 2
Jeng SM, Karger RA, Hodge DO, Burke JP, Johnson DH, Good MS.
The risk of glaucoma in pseudoexfoliation syndrome.
J Glaucoma. 2007 Jan;16(1):117-21.
This is a retrospective community-based study of newly diagnosed cases of PEX
syndrome in all residents of Olmsted County, Minnesota between 1976 and 1991.
The end point was considered the initiation of therapy, which included patients
with glaucoma (optic disc damage or visual field defects), or with elevated
intraocular pressure (IOP) >21 mm Hg in the presence of risk factors. Two
hundred fifty-five patients (318 eyes) had newly diagnosed PEX over the 15-year
interval. Of all PEX patients, 16% were placed on therapy at the time of initial
diagnosis of PEX. In the remaining PEX patients, the probability of being placed
on therapy was 44% at 15 years. The strongest risk factors for converting to
therapy were raised IOP at initial diagnosis of PEX and bilateral involvement.
Level of Evidence – 2
Conclusion – There is level 2 evidence that there is a strong association
between glaucoma and eyes with PEX. The strongest risk factors for
converting to glaucoma are initial raised IOP and bilateral involvement.
Recommendation – D
Systemic Associations of Pseudoexfoliation
Schlotzer-Schrehardt U, Naumann GO.
Ocular and systemic pseudoexfoliation syndrome.
Am J Ophthalmol. 2006 May;141(5):921-937.
An association of PEX syndrome with cardiovascular and cerebrovascular disease
has so far only been established by rather small-scale retrospective studies in
single centres. As inherent to retrospective studies, the accuracy of (early)
diagnoses may
vary or may have been established only without the use of modern diagnostic
techniques. Therefore, a carefully planned prospective, randomized multicenter
study is warranted to finally assess a cause and effect relation of cardiovascular/
cerebrovascular morbidity status and PEX.
7. Pigment Dispersion Syndrome
Evidence Synthesis – There is no evidence synthesis report on this question.
The Guidelines – AOA
Pigment dispersion syndrome occurs in about 2.5 percent of adult Caucasians in
the United States. It rarely occurs in African Americans and Asians. About
20−60% of persons with PDS develop ocular hypertension and 25−50% will
develop pigmentary glaucoma. PDS is usually bilateral and affects persons at
younger ages than POAG (30−50 years). Its occurrence is most common in
Caucasian males with myopia. In fact, about 90 percent of individuals with PDS
are myopic. PDS may have an autosomal-dominant, multifactorial basis,
suggesting the importance of family history. At least one genetic locus has been
identified for PDS.
The Literature
Farrar SM, Shields MB, Miller KN, Stoup CM
Risk factors for the development and severity of glaucoma in the pigment
dispersion syndrome.
Am J Ophthalmol. 1989 Sep 15;108(3):223-9
The authors studied the medical records of patients with pigmentary glaucoma and
pigment dispersion syndrome to identify factors associated with the presence of
secondary glaucoma. Male gender, black race, severe myopia, and Krükenberg
spindles were identified as possible risk factors.
Level of Evidence – 3
Siddiqui Y, Ten Hulzen RD, Cameron JD, Hodge DO, Johnson DH.
What is the risk of developing pigmentary glaucoma from pigment dispersion
syndrome?
Am J Ophthalmol. 2003 Jun;135(6):794-9. Erratum in: Am J Ophthalmol. 2003
Sep;136(3):592.
This is a retrospective community-based study of all newly diagnosed cases of
pigment dispersion syndrome or pigmentary glaucoma over a period of 24 years.
The majority of patients were myopic and mean myopic refractive error was –3.9
± 2.7 dioptres (range, 0.1 to – 12.0 dioptres). The condition was most commonly
diagnosed between the ages of 30 to 49 years. The risk of developing pigmentary
glaucoma from pigment dispersion syndrome was 10% at 5 years and 15% at 15
years. Young, myopic men were most likely to have pigmentary glaucoma. An
IOP greater than 21 mm Hg at initial examination was associated with an
increased risk of conversion.
Level of Evidence – 2
Conclusion – there is a level 2 evidence that male gender, severe myopia and
Krukenberg spindle are risk factor for the development of pigmentary
glaucoma in pigment dispersion syndrome. There is level 3 evidence that a
raised IOP at initial examination is associated with an increased risk of
conversion from pigment dispersion syndrome to pigmentary glaucoma.
Recommendation - D
8. Myopia
Evidence Synthesis – there is not evidence synthesis report on this question
The guidelines
AAO – The association between POAG and myopia has not demonstrated
consistently
Finland – There is a two to four fold risk for development of AOG among
myopes
AOA – Though potentially subject to selection bias, several studies have
demonstrated, after adjustment for age, a two to five fold higher prevalence of
POAG in patients with myopia
The Literature
Mitchell P, Hourihan F, Sandbach J, Wang JJ.
The relationship between glaucoma and myopia: the Blue Mountains Eye Study.
Ophthalmology. 1999 Oct;106(10):2010-5.
In this cross-sectional population-based study of 3654 Australians 49 to 97 years
of age, subjects with myopia were categorized into low myopia (> or =-1.0 D to <3.0 D) or moderate-to-high myopia (> or =-3.0 D). Glaucoma was diagnosed from
characteristic visual field loss, combined with optic disc cupping and rim thinning,
without reference to IOP. Glaucoma was present in 4.2% of eyes with low myopia
and 4.4% of eyes with moderate-to-high myopia compared to 1.5% of eyes
without myopia. After adjusting for known glaucoma risk factors, an association
between myopia and glaucoma remained with odds ratio (OR) 2.3 (95% CI, 1.3 4.1) for low myopia and OR, 3.3(95% CI, 1.7-6.4) for eyes with moderate-to-high
myopia
Only a borderline relationship was found with ocular hypertension, OR of 1.8
(95% CI, 1.2-2.9) for low myopia, and OR of 0.9 (CI, 0.4-2.0) for moderate-tohigh myopia.
Myopia and glaucoma OR 2.3 for low myopia and OR 3.3 for eyes with
moderate-to-high myopia
Myopia and ocular hypertension OR 1.8 for low myopia, and OR of 0.9 for
moderate-to-high myopia.
Level of Evidence - 2
Ramakrishnan R, Nirmalan PK, Krishnadas R, Thulasiraj RD, Tielsch JM, Katz J,
Friedman DS, Robin AL.
Glaucoma in a rural population of southern India: the Aravind comprehensive eye
survey
Ophthalmology. 2003 Aug; 110(8):1484-90
This is a population based cross sectional study of 5150 subjects aged 40 years
and older from 50 clusters representative of three southern districts of Tamil Nadu
in southern India. Myopia was present in 59.3% of POAG patients. This
association was statistically significant on univariate analysis (OR, 1.9; 95% CI,
1.2- 2.9). Multivariate analysis showed a statistically significant association
between POAG and mild myopia (OR, 2.9, 95% CI, 1.3- 6.9), moderate myopia
(OR, 2.1, 95% CI,1.0- 4.6), severe myopia (OR, 3.9, 95% CI,1.6- 9.5).
Myopia and POAG OR, 2.9, moderate myopia OR, 2.1, severe myopia OR, 3.9
Level of Evidence - 2
Xu L, Wang Y, Wang S, Wang Y, Jonas JB.
High myopia and glaucoma susceptibility the Beijing Eye Study.
Ophthalmology. 2007 Feb;114(2):216-20.
This is a study of 4319 subjects, 40 years or older, who agreed to participate when
invited (response rate, 83.4%). The group was stratified according to refractive
error into high myopia (myopia > -8 D), marked myopia (<-6 to -8 D), moderate
myopia (<-3 to -6 D), low myopia (<-0.5 to -3 D), emmetropia (-0.5 to + <2 D),
and hyperopia (>+ 2 D) subgroups. They were evaluated by morphologic
assessment of optic disc monoscopic photographs and measurement of intraocular
pressure. Prevalence of glaucomatous optic nerve atrophy as defined by the
glaucomatous optic nerve head appearance did not vary significantly (p = 0.77;
odds ratio [OR] 1.2( 95% CI, 0.38-3.81) between the highly myopic group and the
group with marked myopia. In both refractive groups combined, glaucoma
frequency was (p = 0.075; OR, 2.28; 95% CI, 0.99-5.25) higher than in the group
with moderate myopia; it was significantly (p = 0.001; OR, 3.5; 95% CI, 1.717.25) higher than in the group with low myopia; significantly (p<0.001; OR, 7.56;
95% CI, 3.98-14.35) higher than in the group with emmetropia; and significantly
(p = 0.005; OR, 4.23; 95% CI, 1.57-11.45) higher than in the group with
hypermetropia. Glaucoma frequency did not vary significantly between the
hyperopic group and the emmetropic group (p = 0.17), the group with low myopia
(p = 0.83) and the group with moderate myopia (P = 0.32). Intraocular pressure
did not vary significantly (P>0.10) between any of the subgroups. Similar results
were obtained for the frequency of glaucoma defined as glaucomatous optic disc
appearance and visual field defects.
Risk of glaucoma high myopia to marked myopia OR 2.28
Risk of glaucoma high myopia to low myopia OR 3.5
Risk of glaucoma high myopia emmetropia OR 7.56
Risk of glaucoma high mypia hypermetropia OR 4.23
Level of Evidence – 2
Conclusion – There is level 2 evidence that increasing levels of myopia are a
risk factor for the development of POAG.
Recommendation - C
9. Central Corneal Thickness
Evidence Synthesis – there is no evidence synthesis report on this question
The Literature
To our knowledge, there are no population studies that have examined central
corneal thickness as a risk factor for the development of glaucoma. Boland and
Quigley pointed out that central corneal thickness has two interactions with OAG
risk. First, it is known that thinner corneas give lower applanation IOP readings,
hence persons with thin corneas would be missed with IOP screening alone and
are more likely to develop optic nerve damage before being detected. On the other
hand, there is recent evidence that those with thinner corneas respond better to
topical medication to lower IOP.
Level of Evidence – 4
Conclusion – There is level 4 evidence that central corneal thickness may be
an indirect risk factor for the development of glaucoma.
Recommendation - D
10. Optic Disc Diameter
Evidence Synthesis – There is no evidence synthesis report on this question
The Literature
Quigley HA, Varma R, Tielsch JM, Katz J, Sommer A, Gilbert DL
The relationship between optic disc area and open-angle glaucoma: the Baltimore
Eye Survey.
J Glaucoma. 1999 Dec;8(6):347-52
Data were collected from a population-based sample of adults residing in East
Baltimore. One eye from each of 75 patients with glaucoma was compared to
those of 3,518 subjects without glaucoma. Although optic disc area was somewhat
larger among patients with glaucoma than control subjects, in a regression model
adjusting for age, gender, and race, the significance of this difference had a
probability of 0.06. It was therefore concluded that disc area is a weak risk factor
for open-angle glaucoma.
Level of Evidence – 2
Conclusion – There is level 2 evidence that the optic disc diameter is a weak
risk factor for the development of open angle glaucoma.
Recommendation - D
11. Ocular Trauma
Strictly, open angle glaucoma due to ocular trauma is classified as secondary
glaucoma. In addition, Boland Quigley did not include it in their review of risk
factors. However, it is included in this report due to its significance in suspecting
glaucoma especially that the eye may look normal or contain a residual sign which
may be overlooked by the examiner.
Evidence Synthesis – There is no evidence base synthesis report on this question
The Literature
Two publications analysed the United States Eye Injury Registry for risk factors
for the development of glaucoma following contusion and penetrating injuries.
These are the only. Other literature attempting to identify risk factors associated
with glaucoma after ocular trauma consists of only a few small case series.
Girkin CA, McGwin G Jr, Long C, Morris R, Kuhn F.
Glaucoma after ocular contusion: a cohort study of the United States Eye Injury
Registry.
J Glaucoma. 2005 Dec;14(6):470-3.
Data from the United States Eye Injury Registry were obtained from a total of
6021 patients who experienced blunt ocular contusion. Cases were defined as
having developed posttraumatic glaucoma within the 6-month follow-up period
based upon the 6-month report form, as determined by the physician submitting
the form. The physician’s opinion was based upon the presence of elevated IOP,
optic disc, and/or visual field abnormality consistent with glaucoma. Specific
information on intraocular pressure, number of medications, need for glaucoma.
The development of glaucoma was independently associated with: advancing age
(OR = 1.02; 95% CI = 1.02, 1.03), visual acuity worse than 20/200 (OR = 1.92;
95% CI = 1.19, 3.10), iris injury (OR = 1.60; 95% CI = 1.05, 2.44), lens injury
(OR = 1.86; 95% CI = 1.11, 3.11), hyphema (OR = 2.23; 95% CI = 1.40, 3.54), or
angle recession (OR = 1.71; 95% CI = 1.00, 2.90).
Level of Evidence – 2
Muallem, MS, Wilensky, J
Glaucoma after Ocular Contusion
J Glaucoma. 2006 Jun;15(3):274
Muallem and Wilensky subsequently wrote to the editor of the Journal of
Glaucoma, commenting on the above study, and expressing concern about the
definition of glaucoma, the inherent wide variability in interpreting visual field
defects and reporting optic disc changes among the large numbers of participating
physicians and the criteria for elevated IOP in terms of level and consistency.
Tumbocon JA, Latina MA.
Angle recession glaucoma.
Int Ophthalmol Clin. 2002 Summer;42(3):69-78.
The authors reviewed the literature and found five studies reporting that more than
60% of eyes with non-penetrating injuries will have some degree of angle
recession. In hyphema patients, based on six studies, some degree of angle
recession occurred in 56% to 100% of cases with a total of 81%. Two studies have
shown that only 6% to 7% of angle recession cases will eventually develop
glaucoma. There appears to be two peak incidences of glaucoma after angle
recession. The first peak occurs within the first few weeks to years after the
trauma and the second peak occurs ten or more years after the injury. Some
investigators have even reported cases of recession glaucoma developing more
than fifty years after the initial injury. There is also an association between the
extent of angle recession and the development of glaucoma. Most investigators
agree that patients with 180 to 360 degrees of angle recession will have a greater
risk of developing late occurring glaucoma. It appears that those eyes with less
than 180 degrees of recession are unlikely to develop glaucoma. In eyes that do
develop angle recession glaucoma, the contralateral non-traumatised eye has been
reported to have a 50% chance of developing open-angle glaucoma, sometimes
years after the pressure rise was noted in the traumatized eye. This may indicate that
the angle recession itself is probably not the cause of elevated intraocular pressure but, rather,
that it may accelerate the appearance of glaucoma in patients who are already
predisposed to develop primary open-angle glaucoma.
Level of Evidence - 3
Girkin CA, McGwin G Jr, Morris R, Kuhn F.
Glaucoma following penetrating ocular trauma: a cohort study of the United
States Eye Injury Registry.
Am J Ophthalmol. 2005 Jan;139(1):100-5.
This is prospective cohort study in which data from the United States Eye Injury
Registry was obtained from a total of 3,627 patients who experienced penetrating
ocular injury between 1988 and January 2003. Data are collected from hospitals,
emergency rooms, and physicians’ offices on all types of trauma determined as
serious eye trauma, defined as trauma that may potentially result in permanent
structural or functional damage. A standardized reporting form is filled out on the
initial examination of a patient with ocular trauma. Information regarding
demographics, the nature and location of injury, the extent of ocular injury
assessed both structurally and functionally, and any initial surgical interventions
are recorded on the initial visit after the traumatic injury. At 6 months, an
additional form is filled out encompassing information regarding the structural
and functional ocular outcomes resulting from the initial trauma and any
additional procedures that have occurred. The risk of developing posttraumatic
glaucoma was 2.67%. The development of glaucoma was independently
associated with several baseline characteristics
including advancing age (relative risk 1.02/yr 95% confidence interval [1.00,
1.03]), lens injury (1.56 [1.03, 2.35]), poor baseline visual acuity (2.59 [1.62,
4.14]), and inflammation (3.02 [1.52, 6.02]).
Level of Evidence – 2
Conclusion – There is level 2 evidence that advancing age, lens injury and
poor baseline visual acuity are risk factors for the development of glaucoma
following both contusion and penetrating injuries. In addition, angle
recession, hyphema and iris injury are risk factors in contusion injuries and
inflammation is a risk factor in penetrating injuries.
Recommendation - D
Systemic Diseases
12. Hypertension
Evidence Synthesis – there is no evidence synthesis report on this question
The Guidelines
AAO – There appears to be a subset of patients with low diastolic perfusion
pressure (diastolic blood pressure – IOP) who are at a higher risk for POA
Finland – Decreased perfusion pressure together with age give a threefold risk of
developing open angle glaucoma
AOA - The literature is equivocal on whether there is an association between
systemic hypertension and POAG. The Baltimore Eye Survey suggested the
complexity of the relationship between POAG and systemic blood pressure.
Patient age and the duration of systemic hypertension modify its effect on POAG.
Lower perfusion pressure (BP-IOP) was significantly associated with an increased
prevalence of POAG. Low systemic blood pressure, including the nocturnal dip,
also may pose a risk for NTG.
The Literature
Wong TY, Mitchell P.
The eye in hypertension.
Lancet. 2007 Feb 3;369(9559):425-35. Review. Erratum in: Lancet. 2007 Jun
23;369(9579):2078. Wong, Tien
Systemic hypertension is suspected to increase the risk of the development and
progression of glaucoma. Epidemiological studies have not, however, shown a
consistent association between hypertension and glaucoma. Three populationbased studies reported a cross-sectional association. In one, people with
hypertension were 50% more likely to have glaucoma, after adjustment for
glaucoma risk factors such as intraocular pressure, than those without.
Hypertension also accounted for the greatest population-attributable risk for
glaucoma compared with other risk factors, suggesting that from a public-health
perspective, hypertension might be more important than less common risk factors
carrying a two-fold to three-fold higher risk of glaucoma. Nonetheless,
prospective studies have not proven an association between both systolic or
diastolic blood pressure and incidence of glaucoma. Perfusion pressure is the
difference between the diastolic blood pressure and intraocular pressure. One
study noted that low perfusion pressure was a stronger risk factor for glaucoma
than was systemic hypertension alone and that hypertension was a risk factor for
glaucoma in older participants, but not in those who were younger.
Level of Evidence – Level 2
Conclusion – It is not yet confirmed that hypertension is a risk factor for the
development of POAG.
Recommendation for Hypertension - D
Recommendation for Perfusion Pressure - C
13. Diabetes
Evidence Synthesis
Bonovas S, Peponis V, Filioussi K
Diabetes mellitus as a risk factor for primary open-angle glaucoma: a metaanalysis.
Diabet Med. 2004 Jun;21(6):609-14
This meta-analysis included twelve studies published between 1987 and 2001
(five
case–control studies and seven cross-sectional studies). Eleven studies reported
positive association (OR > 1) and one study reported negative association (OR <
1). However, only five of the positive studies had estimated ORs that were
statistically significant. The one study reporting negative association was not
statistically significant. The association of diabetes mellitus with primary openangle glaucoma was found to be statistically significant using either a random
effects model, OR =1.50, (95% CI, 1.16-1.93), or a fixed-effects model, OR =
1.27 (95% CI, 1.10-1.45).
The Guidelines – AOA
The association of diabetes mellitus with both elevated IOP and POAG has been
controversial. Several studies lend support to a higher prevalence of ocular
hypertension and POAG in persons with diabetes, for whom the relative risk of
POAG ranges from 1.6 to 4.7. Others have found no relationship between the
presence of diabetes and the development of ocular hypertension or POAG.
The Literature
In relation to the above meta-analysis, Boland and Quigley pointed out that the
report did not standardise the definition of OAG and two of the included studies
used IOP as a defining feature of OAG.
Level of Evidence – 1
Conclusion – It is not yet definite that diabetes is a risk factor for the
development of POAG.
Recommendation – B (guarded due to problems affecting quality of metaanalysis)
14. Thyroid Disease
Evidence Synthesis – There is no evidence synthesis report on this question
The Literature
Lee AJ, Rochtchina E, Wang JJ, Healey PR, Mitchell P
Open-angle glaucoma and systemic thyroid disease in an older population: The
Blue Mountains Eye Study.
Eye. 2004 Jun;18(6):600-8.
In this population based study of 3654 persons, aged 49-97 years, AOG was more
frequent in those reporting past thyroid disease but the relationship was not
statistically significant. OAG was significantly more frequent in subjects reporting
current thyroxine use, multivariate OR 2.1; 95% CI 1.0-4.4, or history of thyroid
surgery multivariate OR 2.5; 95% CI 1.0-6.2.
Level of Evidence – Level 2
Girkin CA, McGwin G, McNeal SF, Lee PP, Owsley C.
Hypothyroidism and the development of open-angle glaucoma in a male
population.
Ophthalmology. 2004 Sep;111(9):1649-52.
This is a case control study in which 590 patients newly diagnosed with OAG
were age matched with controls. After adjustment for the other potential risk
factors, patients were significantly more likely to have prior hypothyroidism than
controls (OR, 1.40; 95% CI, 1.01-1.97).
The authors mentioned that there were previously published five small case
control studies with some showing a significant positive association and others
finding no greater risk of glaucoma in patients with hypothyroidism. However,
these previous studies utilized a small number of subjects, with varying study
designs and different definitions for both glaucoma and hypothyroidism, resulting
in an unclear impression of the true relationship between hypothyroidism and the
development of open-angle glaucoma (OAG).
Level of Evidence – Level 2
Conclusion – An association between POAG and hypothyroidism has been
found but the role of hypothyroidism as a risk factor for the development of
POAG is not known.
Recommendation - D
15. Cardiovascular Disease
Evidence Synthesis – There is no evidence synthesis report on this question
The Literature
Boland and Quigley pointed out that despite the presence of several articles
examining the risk of OAG in cardiovascular disease, diagnostic definitions have
varied and are difficult to standardise. With one exception, major population
studies and clinical trials have generally failed to find any association of
cardiovascular disease with OAG, nor is there evidence of premature mortality in
OAG patients as might occur if they had predispositions to cardiovascular disease.
Evidence – Level 2
Orzalesi N, Rossetti L, Omboni S; on behalf of the OPTIME Study Group
(Osservatorio sulla Patologia glaucomatosa, Indagine Medico Epidemiologica),
CONPROSO (Collegio Nazionale dei Professori Ordinari di Scienze
Oftalmologiche).
Vascular risk factors in glaucoma: the results of a national survey.
Graefes Arch Clin Exp Ophthalmol. 2007 Jun; 245(6):795-802.
This is an observational survey in 35 Italian academic centres examining 2,879
POAG patients and 973 controls. The ESH-ESC (European Society of
Hypertension-European Society of Cardiology) guidelines were used to calculate
the level
of cardiovascular risk. POAG patients tended to have a higher cardiovascular
risk than controls: 63% of glaucoma cases vs 55% of controls (OR:1.38, p=0.005)
had a “high” or “very high” cardiovascular risk.
Level of Evidence – Level 2
Conclusion – POAG patients may have a higher cardiovascular risk than
controls but there is no evidence that cardiovascular disease is a risk factor
for the development of POAG.
Recommendation - D
16. Sleep Apnea
Evidence Synthesis – There is no evidence synthesis report on this question
The Literature
McNab AA.
The eye and sleep apnea.
Sleep Med Rev. 2007 Aug;11(4):269-76.
The author reviewed the literature and found a report that has identified increased
prevalence of primary open angle glaucoma in patients with obstructive sleep
apnea (OSA) and also a report of high prevalence of sleep-disordered breathing in
patients with primary open angle glaucoma. One study showed a correlation
between the severity of the sleep disturbance and severity of the visual field loss.
Others have reported an association between normal-tension glaucoma and OSA,
particularly in older patients. A variety of visual field defects in OSA patients was
also reported in nine patients, and in two patients who were treated for OSA, the
field defects stabilised. Another patient has also been reported with normaltension glaucoma and progressive field loss despite pressure lowering by drops
and surgery, whose field loss stabilised after diagnosis of OSA and its treatment.
Against this background of reports, one conflicting study has shown the
prevalence of glaucoma in a group of OSA patients to be the same as the general
population. The author concluded that this may be an optic neuropathy that
mimics glaucoma and that it would seem prudent to ask for symptoms of OSA in
patients with an optic neuropathy especially those in whom there is no other
identifiable risk factor of glaucoma.
Level of Evidence – Level 2
Conclusion – Sleep apnea as a risk factor for the development of POAG has
not been confirmed but sleep apnea may be associated with an optic
neuropathy.
Recommendation – D
Migraine and Vasospasm
17. Migraine
Evidence Synthesis – There is no evidence synthesis report on this question
The Literature
Phelps CD, Corbett JJ.
Migraine and low-tension glaucoma. A case-control study.
Invest Ophthalmol Vis Sci. 1985;26:1105–1108.
In this study, headaches were present in 86% of elderly low-tension glaucoma
patients (70 yr of age or older) but in only 64% of elderly normal subjects (P =
0.04) and only 59% of elderly ocular hypertensive patients (P = 0.02).
Level of Evidence – Level 2
Klein BE, Klein R, Meuer SM, Goetz LA.
Migraine headache and its association with open-angle glaucoma: the Beaver Dam
Eye Study.
Invest Ophthalmol Vis Sci. 1993 Sep;34(10):3024-7
In this population based study, there was no difference in the frequency of openangle glaucoma between those with and those without migraine headache (P =
0.87). Multivariate analyses did not alter the conclusion.
Level of Evidence – Level 2
Wang JJ, Mitchell P, Smith W.
Is there an association between migraine headache and open-angle glaucoma?
Findings from the Blue Mountains Eye Study.
Ophthalmology. 1997;104:1714–1719.
In this population based cross sectional study of subjects 49 years old and older.
For all age groups combined, there was no significant association between typical
migraine headache and OAG. However, after stratifying into 10-year age groups,
increased odds for OAG were found for people giving a history of typical
migraine headache and aged 70-79 years (OR, 2.5; 95% CI 1.2-5.2), after
adjusting for variables found associated with glaucoma.
Level of Evidence – Level 2
Cursiefen C, Wisse M, Cursiefen S, Jünemann A, Martus P, Korth M.
Migraine and tension headache in high-pressure and normal-pressure glaucoma.
Am J Ophthalmol. 2000 Jan;129(1):102-4.
This is a prospective study in which 154 patients with glaucoma (56 normalpressure subgroup and 98 high-pressure glaucoma subgroup), 55 patients with
ocular hypertension and 75 control subjects were analyzed by means of a
standardized questionnaire based on International Headache Society criteria. The
prevalence of headache, migraine, and tension headache did not vary significantly
among control subjects, patients with ocular hypertension and patients with
glaucoma, but migraine was significantly more common in patients with normalpressure glaucoma (28%) compared with control subjects (12%; P<.05) and
patients with high-pressure glaucoma (10%; P<.01).
Level of evidence – 2
Conclusion – There is level 2 evidence that headaches are more common in
elderly patients with low tension glaucoma and that there is increased odds of
OAG in elderly people with migraine headache that those without. For all age
groups, there is no difference in the occurrence of glaucoma between those
with and without migraine headaches, but migraine is significantly more
common in patients with normal tension glaucoma than controls or patients
with high tension glaucoma.
Recommendation – C
18. Raynaud’s Phenomenon
Evidence Synthesis – There is no evidence synthesis report on this question
The Literature
Boland and Quigley explained that on the basis of the vascular theory of
glaucoma, systemic manifestations of vasospasm have been studied as a possible
risk factor. They found that an earlier report suggested a link between vasospastic
phenomena and certain types of optic nerve damage (see below), but that the Early
Manifest Glaucoma Trial did not confirm an association.
Broadway DC, Drance SM.
Glaucoma and vasospasm.
Br J Ophthalmol. 1998 Aug;82(8):862-70.
Patients with pure examples of four glaucomatous optic disc types--focal
ischaemic, myopic glaucomatous, senile sclerotic, and those with generalised cup
enlargement, were selected. A detailed ophthalmic, systemic, drug and smoking
history was taken from the patients who, in addition, underwent assessment of
peripheral vasospasm with a laser Doppler flowmeter. The group of patients with
focal ischaemic discs contained more women (66% versus 32%-50% in the other
three groups; p = 0.01) and had a higher prevalence of vasospasm (63% versus
25%-49%; p = 0.01), migraine (32% versus 8%-19%; p = 0.02), and cold
extremities (66% versus 17%-30%; p = 0.00003). The authors also noted that the
simple assessment as to whether a glaucoma patient suffers from colder
extremities than average appeared to be better at distinguishing the focal
ischaemic type of glaucoma than using the laser Doppler flowmeter.
Evidence Level – 3
Conclusion – Vasospasm, migraine and cold extremities may be associated
with focal ischaemic discs.
Recommendation - D
Non-Glaucoma Medications
19. Corticosteroids
Evidence Synthesis – There is no evidence synthesis report on this question
The Literature
Jones R 3rd, Rhee DJ
Corticosteroid-induced ocular hypertension and glaucoma: a brief review and
update of the literature.
Curr Opin Ophthalmol. 2006 Apr;17(2):163-7.
The authors reviewed the literature of corticosteroid induced ocular hypertension
and glaucoma and its risk factors. They found that increased intraocular pressure
can occur as a consequence of oral, intravenous, inhaled, topical, periocular,
or intravitreal corticosteroid therapy. If the ocular hypertension is of a significant
magnitude, not recognized and not treated, subsequent glaucomatous optic
neuropathy can develop. The rise of raised IOP usually occurs over a period of
weeks if used topically and years if used systemically. There have been some
reports of an elevation of IOP within hours of initiating intensive topical steroid
use.
Corticosteroids have been shown to exert an ocular hypertensive response relative
to the intraocular potency of the steroid. Acetates are more lipophilic and
penetrate through the cornea better than phosphates, which are relatively
hydrophilic.
Medrysone 1.0% caused a 1.0 mmHg rise in IOP, while more potent steroids such
as prednisolone acetate 1.0% and dexamethasone acetate 0.1% caused a 10 and
22 mmHg rise in IOP, respectively.
As regards predisposing risk factors for corticosteroid induced glaucoma , they
found the following.
Primary open-angle glaucoma patients and glaucoma suspects were shown to be at
an increased risk for elevated IOP after treatment with topical dexamethasone
0.1% for four weeks or betamethosone 0.1% for two to four weeks. In the
dexamethasone study, the effect was noted to be more prominent in the eyes of
older adult patients compared with the eyes of younger adult patients. Two other
studies showed that
simply having a first-degree relative with POAG could make one susceptible to
being a steroid-responder, one of which was a double blind study performed in
Whipps Cross Hospital, London by TG Davies*. In this study, disodium
phosphate betamethasone 0.1% was instilled four times daily into one eye, and
normal saline into the fellow eye of close relatives of patients with chronic simple
glaucoma. (Addition by author of report)
Although older patients are at increased risk, the frequency of steroid
responsiveness with age may occur in a bimodal distribution. Children as a group
have been shown to be greater steroid-responders as compared with adults.
Patients with connective tissue disease tend to be steroid-responders. Men with
connective-tissue disease tended to be greater responders, although gender is not
typically considered a risk factor in people without connective-tissue disease.
Additionally, patients with type-1 diabetes mellitus and high myopia have also
been shown to be at increased risk to be steroid-responders.
* Davies TG.
Tonographic survey of the close relatives of patients with chronic simple
glaucoma.
Br J Ophthalmol. 1968 Jan;52(1):32-9.
Conclusion - Increased intraocular pressure can occur as a consequence of
oral, intravenous, inhaled, topical, periocular, or intravitreal corticosteroid
therapy. Children, older adult patients, close relatives of glaucoma patients,
men with connective tissue disease and patients with diabetes mellitus or high
myopia are at high risk of being steroid responders.
No evidence level or recommendation due to the narrative nature of the
review.
20. Cholesterol Lowering Agents
Evidence Synthesis – There is no evidence synthesis report on this question
The Literature
McGwin G Jr, McNeal S, Owsley C, Girkin C, Epstein D, Lee PP.
Statins and other cholesterol-lowering medications and the presence of glaucoma.
Arch Ophthalmol. 2004;122:822–826.
This study is based on the records of an administrative clinical database. Cases
were all male patients aged 50 years and older with a new diagnosis of glaucoma
on an outpatient or inpatient visit between January 1, 1997, and December 31,
2001. Each case was age matched to 10 control subjects. Longer duration of statin
use was associated with a lower risk of open-angle glaucoma primarily among
subjects with 24 months or more of use (OR, 0.60; 95% CI, 0.39-0.92). Nonstatin
cholesterol-lowering agents were also associated with a reduced risk of having
open-angle glaucoma.
Level of Evidence – 2
Conclusion – Statin and non-statin cholesterol lowering agents may be
associated with a reduced risk of developing open angle glaucoma.
Recommendation - D
21. Calcium Channel Blockers
Evidence Synthesis – There is no evidence synthesis report on this question
The Literature
Boland and Quigley reviewed the literature and found that calcium channel
blockers have been used in some clinical trials of small subgroups of OAG
patients and ‘shown to lower IOP when used topically’ (Report author addition).
They also mentioned that no data from population studies have indicated either
beneficial or detrimental effects of these agents.
Evidence Level – 1 to 2
Conclusion – The role of calcium channel blockers as a risk factor for
developing OAG is not known.
Recommendations - C
Personal Behaviours
22. Exercise
Evidence Synthesis – There is no evidence synthesis report on this question
The Literature
Boland and Quigley reviewed the literature and concluded that although exercise
has shown the ability to lower IOP in adults with ocular hypertension, no direct
association with OAG risk has been made.
Evidence Level – 2
Conclusion – There is not direct association between exercise and glaucoma
risk.
Recommendation - D
23. Smoking
Evidence Synthesis
Bonovas S, Filioussi K, Tsantes A, Peponis V
Epidemiological association between cigarette smoking and primary open-angle
glaucoma: a meta-analysis
Public Health. 2004 Jun;118(4):256-61
This meta-analysis included seven studies. Results suggest that current smokers
are at significantly increased risk of developing POAG, odds ratio (OR) 1.37
(95% CI, 1.00 –1.87). In contrast, past smokers are not elevated risk of developing
POAG, OR 1.03 (95% CI, 0.77–1.38). It should be noted that this meta-analysis
did not include a definition for POAG. Also Boland and Quigley pointed out that
this meta-analysis includes clinic based data from Africa and that one small clinic
based case control series found that Chinese OAG exhibit more cigarette smoking
than controls; suggesting that some OAG risk factors might be dependant on
interaction with ethnicity.
Evidence Level – 1
Conclusion – Smokers may be at a significantly increased risk of developing
POAG
Recommendation - B
24. Obesity
Evidence Synthesis – There is no evidence synthesis report on this question
The Literature
Cheung N, Wong TY
Obesity and eye diseases.
Surv Ophthalmol. 2007 Mar-Apr;52(2):180-95.
In this study, the authors reviewed 11 studies on the relation between body mass
index and ocular hypertension or glaucomatous optic neuropathy. They found as
strong evidence that obesity is associated with elevated intraocular pressure, but
there was no convincing data to support a more direct association between obesity
and glaucomatous optic neuropathy. One study suggested some protective effect
of higher BMI with risk of open-angle glaucoma. The reviewers mentioned that
the analysis, however, only controlled for age and not other factors, and the
possibility of incomplete adjustment for confounders could not be excluded.
Evidence Level for obesity and OHT – 2
Evidence Level for protective effect – 2
Conclusion - Inconsistent Findings – no recommendation
25. Alcohol
Evidence Synthesis – There is no evidence synthesis report on this question
The Literature
Klein BE, Klein R, Ritter LL
Relationship of drinking alcohol and smoking to prevalence of open-angle
glaucoma. The Beaver Dam Eye Study
Ophthalmology. 1993 Nov;100(11):1609-13
This is a population-based survey of 4926 persons 43 to 84 years of age in Beaver
Dam, Wisconsin. Heavy drinking behaviour was not related to the prevalence of
open angle glaucoma.
Level of Evidence - 2
Kang JH, Willett WC, Rosner BA, Hankinson SE, Pasquale LR
Prospective study of alcohol consumption and the risk of primary open-angle
glaucoma
Ophthalmic Epidemiol. 2007 May-Jun;14(3):141-7
The authors followed female nurses from 1980 and male health professionals from
1986 to 2002, who were 40 years or older, did not have POAG, and reported
receiving eye examinations during follow-up. Alcohol consumption of less than
30 g/day did not influence POAG risk. Although there were suggestive inverse
associations with drinking more than 30 g/day (RR=0.71), this was not significant
(95% CI, 0.49-1.04), and no significant linear associations were detected between
alcohol consumption and AOG.
Level of Evidence – 2
Conclusion – There is no significant association between alcohol consumption
and POAG.
Recommendation - C
26. Caffeine
Evidence Synthesis – There is no evidence synthesis report on this question
The Literature
Boland and Quigley reviewed the literature and found that caffeine intake has not
been related to OAG, although acute intake of a large volume of caffeine
containing
beverage does cause a slight rise in IOP.
Level of Evidence – 2
Conclusion – There is no evidence of an association between caffeine intake
and POAG.
Recommendation - D
27. Fat Intake
Evidence Synthesis – There is no evidence synthesis report on this question
The Literature
Kang JH, Pasquale LR, Willett WC, Rosner BA, Egan KM, Faberowski N,
Hankinson SE.
Dietary fat consumption and primary open-angle glaucoma.
Am J Clin Nutr. 2004 May;79(5):755-64
In this study, the authors studied dietary fat consumption because dietary fatty
acids affect endogenous prostaglandin F(2alpha) concentrations and may thus
influence intraocular pressure. They prospectively followed up 76199 women
nurses for 16 years and 40306 men health professionals for 10 years who were 40
years or older and free of POAG at the time of enrolment. Major fats and fat
subtypes were not independently associated with POAG risk. A high ratio of n-3
to n-6 polyunsaturated fat appeared to increase the risk of POAG, particularly
high-tension POAG.
Level of Evidence – 2
Conclusion – Major fats and fat subtypes are not associated with POAG
risk.
Recommendation - D
28. Increased Venous Pressure
Evidence Synthesis – There is no evidence synthesis report on this question
The Literature
Boland and Quigley reviewed the literature on elevated venous pressure and OAG
and concluded that there is some epidemiologic evidence that this may play a role
in OAG, but clinic-based studies have not confirmed a general tendency.
Level of Evidence – 2 to 3
Conclusion – A role of increased venous pressure in the development of
POAG has not been confirmed.
Recommendation – D
Summary Table of Risk Factors for Glaucoma
Level of
Recommendation
A
B
C
D
Condition
Age
Gender
Ethnicity
Diabetes
Smoking
Family History
Raised IOP
Myopia
Perfusion Pressure
Migraine
Calcium Channel Blockers
Alcohol
Exfoliation Syndrome
Pigment Dispersion Syndrome
Central Corneal Thickness
Optic Disc Diameter
Ocular Trauma
Hypertension
Thyroid Disease
Cardiovascular Disease
Raynaud’s Phenomenon
Cholesterol Lowering Agents
Exercise
Caffeine
Fat Intake
Increased Venous Pressure
Number in
Text
1
2
3
13
23
4
5
8
12
17
21
25
6
7
9
10
11
12
14
15
16
20
22
26
27
28
No Recommendation Corticosteroids
Obesity
19
24
II Risk of progression of ocular hypertension to glaucoma
Friedman DS, Wilson MR, Liebmann JM, Fechtner RD, Weinreb RN.
An evidence-based assessment of risk factors for the progression of ocular
hypertension and glaucoma.
Am J Ophthalmol. 2004 Sep;138(3 Suppl):S19-31.
In this review, the authors examined 34 studies, including the Ocular
Hypertension Treatment Study critically for strength of evidence to ascertain risk
factors for progression of OHT to glaucoma and the progression of glaucoma to
blindness. The latter will be discussed in the next section.
For the progression of ocular hypertension to glaucoma the authors analysed 8
studies.
Mean intraocular pressure was found to be a significant risk factor for
progression. In the OHTS, univariate and multivariate analyses found that every 1
mmHg increase in mean IOP level was associated with a 10% increased risk of
progression from OHT to glaucoma. One study reported that a large difference in
IOP levels between the two eyes was associated with progression from OHT to
glaucoma. In an unrelated study, such large disparities between the two eyes were
reported to be more common in patients with OHT (33%) and POAG (36%), than
in normal subjects (6%). The significance of diurnal or nocturnal fluctuation of
IOP is still questionable.
Greater cup to disc ratio is an independent risk factor for progression from OHT
to glaucoma. Evidence was strong and consistent. Greater cup to disc ratio has
been identified as a baseline risk factor in two studies, with values > 0.4 and = or
>0.5 being associated with an increased risk of progression. The OHTS univariate
hazard ratios were increased by a significant 25% per 0.1 larger horizontal cup to
disc ratio and by 32% per 0.1 larger vertical cup to disc ration. Statistical
significance was confirmed in multivariate analysis. One edit orial however
warned that large cup to disc ratios in OHT patients in general and in OHTS
specifically may be an indication of early structural damage and not a risk factor,
particularly that after selecting the OHT patients, 20% of them were found to have
defects on short wave length automated perimetry. Entry into the study was based
on a normal and reliable Humphrey 30-2 visual fields.
Nerve fibre layer atrophy was associated with increasing risk of development of
visual field loss among persons with ocular hypertension. The grade of atrophy
was strongly predictive with OR around 8 for more severe nerve fibre defects.
Central corneal thickness was identified in the OHTS as a strong independent
risk factor for progression from OHT to POAG in both univariate and multivariate
analysis, Hazard Ratio 1.88 (95% CI, 1.55 – 2.29) and 1.71 ( 95% CI, 1.40 – 2.09)
respectively.
Age is an independent risk factor for progression of OHT, as evidenced by
multiple progression studies.
Black race, although associated with increased risk for AOG; there is little
evidence that it is an independent risk factor for progression from OHT to
glaucoma. In OHTS, black race was associated with an increased risk of
progressing from OHT to glaucoma in the univariate analysis but not in the
multivariate analysis.
Family history, although associated with increased risk of AOG; evidence is
lacking regarding progression from OHT to glaucoma. In OHTS, family history
was not identified as a risk factor, however, family history was ascertained by
patient report and not by direct examination of relatives. One large cohort study of
Greek subjects with OHT did find family history to be associated with progression
to visual field loss.
Diabetes had a weak evidence of being a risk factor in progression from OHT to
glaucoma. Analysis of the OHTS results suggested that diabetes protects against
progression to glaucoma. However, these unexpected findings may in part be
explained by the fact that patients with diabetic retinopathy were excluded
from this study, yielding an unrepresentative group of patients with diabetes. Also,
the diagnosis of diabetes was by self-report and not clinically verified, which
could result
in inaccuracies in reporting.
Decreased outflow facility, migraine, myopia, hypermetropia,
pseudoexfoliation and male sex, have been mentioned in the literature as risk
factor for the progression of OHT. In general, the limited number of studies in
which these additional suspected risk factors were evaluated does not support firm
conclusions concerning their relative importance.
III Risk factors for the progression of chronic open glaucoma to blindness
For the progression of glaucoma to blindness, the authors analysed 4 studies
namely, the Early Manifest Glaucoma Trial (EMGT), The Advanced Glaucoma
Intervention Study (AGIS), the Collaborative Normal Tension Glaucoma Study
(CNTGS) and the Collaborative Initial Glaucoma Treatment Study (CIGTS).
Older age was found to be a risk factor for the progression of glaucoma in three
of the studies. The fourth, CNTGS, did not find an association.
Diabetes was found to be a risk factor by AGIS and CIGTS. The other two studies
did not examine diabetes for risk.
Disc haemorrhage was found to be a risk factor by EMGT and CNTGS. The
other two studies did not examine disc haemorrhage for risk
Female sex was found to be a risk factor in the CNTGS. Male sex was found to
be a risk factor in the AGIS. EMGT and CIGTS did not examine gender for risk.
Intraocular pressure was found in the EMGT to be a risk factor for progression
at 21 mmHg or higher. Greater IOP reduction at the first follow up visit after three
months for both treated and untreated patients was associated with a lower risk of
progression. In CNTGS and AGIS, the level at intraocular pressure at baseline
was not a risk factor. The CIGTS did not examine IOP as a risk factor.
Pseudoexfoliation was found to be a risk factor in EMGT. The other three studies
did not examine pseudoexfoliation as a risk factor.
Race was found to be a significant risk factor in the CNTGS with Asians having a
significantly longer survival time before blindness compared to Caucasions. Black
race appeared to show more rapid deterioration than Caucasians; however this
difference did not reach statistical significance due to the small number of black
patients enrolled. In the CIGTS, being non white was a risk. The EGIS did not
find an association.
Greater visual field loss was found to be a risk factor for progression of
glaucoma the EMGT. The AGIS found that better visual field is the risk factor
which is the opposite of the findings of EMGT. The other two studies did not
examine the degree of visual field loss as a risk factor.
Lower formal education was found to be a risk factor for the progression of
glaucoma by AGIS.
Migraine was an independent risk factor for the progression of glaucoma in
CNTGS. The EMGT did not find it significantly related.
Raynauld’s syndrome was not a significant risk factor for the progression of
glaucoma in EMGT.
Systemic hypertension was not a significant risk factor for the progression of
glaucoma in AGIS.
Systemic diseases were not a significant risk factor for the progression of
glaucoma in AGIS.
Refractive errors were not a significant risk factor for the progression of
glaucoma in AGIS.
Central corneal thickness was not a significant risk factor for the progression of
glaucoma in the EMGT.
Behki R,. Damji KF, Crichton A for the CCT workshop participants
Canadian perspectives in glaucoma management: the role of central corneal
thickness
Can J Ophthalmol. 2007; 42 (1): 66-74.
Other studies have shown relatively lower CCTs among ocular hypertensives with
abnormal perimetry results in SWAP or FDT, compared with subjects with normal
results. There are seven studies, besides EMGT, which are related to CCT and
POAG.
In one study, increased CCT correlated significantly (p>0.001) and positively with
the area of the neuroretinal rim and negatively with the presenting loss of visual
field. Some of the other studies showed a weak association between thinner
corneas and glaucoma progression
Detection
Why is the detection of glaucoma included in this report?
The detection of chronic open angle glaucoma, ocular hypertension and glaucoma
suspects is first contact care. In the UK, this type of first contact, where glaucoma
is definitively diagnosed, suspected or excluded, is usually in the hospital eye
service. Traditionally, the optometrists suspected glaucoma by a raised IOP
finding or a suspiciously cupped optic disc and referred the patient to the hospital
eye service for glaucoma detection. But now there are changes. Firstly, some
optometrists have acquired advanced technologies. Secondly, Primary Care Trusts
are increasingly establishing ophthalmic primary care units where they would
expect glaucoma detection to take place. Thirdly, there may be private providers
who are offering a glaucoma detection service in the community.
Background
The detection of glaucoma in primary care is different to that in the hospital eye
service because it is the first level of capturing the disease. Whereas the hospital
doctor will have glaucoma at the forefront of his differential diagnosis because the
patient has already been suspected of having glaucoma in primary care, the
primary care ophthalmologist will not have this advantage. S/He may not proceed
with tests like visual field testing or close examination of the optic disc and nerve
fibre layer unless he has a strong reason to suspect glaucoma.
In this report therefore, all the steps leading to detection will be analysed fully for
evidence, even if these steps have not traditionally be included with rigour in the
examination of the possible glaucoma patient. For each step, elaboration in any of
the clinical guidelines will be mentioned, followed by a presentation of evidence
to date. The level of evidence and degree of recommendation will be included in
the end.
The following steps will be presented
1. History Taking
2. Visual Acuity
3. Colour Vision
4. Contrast Sensitivity
5. Visual Disabitily
6. Relative Afferent Pupillary Defect
7. Water Drinking Test
8. Central Corneal Thickness
9. Measurement of intraocular pressure
10. Gonioscopy
11. Pupil Dilatation
12. Optic Disc Examination
13. Examination of the Nerve Fibre Layer
14. Visual Field Testing
1. History Taking
Key Question
Is there evidence of specific questions in history taking that would help in the
diagnosis of ocular hypertension, glaucoma suspect or chronic open angle
glaucoma?
Evidence Synthesis – There is no evidence synthesis report on this question
The Guidelines
ICO – recommends including the following in history taking





Ocular history (A:III)
Systemic history (A:III)
Family history (A:II)
Assessment of impact of visual function on daily living and activities
(A:III)
Review of pertinent records (A:III)
AAO – Recommends including the following in history taking









Ocular history (A:III)
Family history (A:II)
Systemic history (A:III)
Assessment of the impact of visual function on daily living and activities
(A:III)
Review of pertinent records with particular reference to the status of the
optic
nerve, visual field, and IOP (A:III)
History of ocular surgery (A:III)
The use of ocular or systemic medications (A:III)
Known local or systemic intolerance to glaucoma medications (A:III)
Outcome of glaucoma in family members including history of visual loss
from
glaucoma (B:III)
Singapore – No mention
RCOphth – No mention
Asia Pacific – recommends including the following in history taking


Past ophthalmic history of steroids, surgery and laser
Visual symptoms of blurring and discomfort (Posner-Schlossman and
pigment dispersion syndromes), glare and coloured rings around lights
from corneal oedema, poor light dark adaptation and difficulty tracing fast
moving objects (tennis or golf ball)

Past medical history
o Respiratory - asthma and chronic obstructive pulmonary diseases
associated with hyperresponsive airways and/or reduced lung capacity.
o Cardiovascular – to exclude past haemodynamic crisis (post partum
haemorrhage, ruptured abdominal aneurysm, severe trauma that may
cause optic disc colour cupping that mimics glaucoma but is not
progressive
o Cardiovascular – cardiac arrythmias e.g. heart block which may
preclude the use of β blockers or α agonists
o Cardiovascular – hypertension overtreatment may worsen glaucoma
risk and progression. Systemic β blockers may mask elevated IOP
o Cardiovascular - vasospastic tendency (migraine and Raynaud’s
syndrome) may be associated with increased incidence and severity of
glaucoma, especially normal pressure.
o Endocrine – diabetes associated with open angle and neovascular
glaucoma
o Endocrine - thyroid eye disease
o Endocrine – pituitary tumours
o CNS – previous CVA/head injury/pituitary lesions may cause field loss
o CNS – early dementia - affects compliance, understanding and insight
into the disease
o Musculoskeletal – arthritis ( osteo and musculoskeletal) may affect
severely the ability to administer eye drops
o Urogenital – urinary stones may limit carbonic anhydrase inhibitors
o Ocular trauma – angle recession, lens dislocation, choroidal/retinal
damage
o Pregnancy and lactation – if present or possible renders all
interventions potentially hazardous
o Medication – steroids – any route of administration is associated with
ocular hypertension or open angle glaucoma. It is sometimes found in
traditional medicines
o Medication – Vigabatrin (anti convulsant)- linked to nasal peripheral
loss without disc changes
o Medication – systemic β blocker/calcium channel blockers – may
interact with topical β blockers

Family History of the glaucoma, its type and its course in the family
European Glaucoma Society – Recommends including the following in the
history




History of migraine
History of cold hands and Raynaud’s disease,
History of neurological disease, thyroid disease, kidney disease or blood
loss, Smoking and drinking habits
Family history of visual loss and glaucoma
Finland – No mention
AOA - The patient history should include a thorough analysis of all general
familial, ocular, and nonocular risk factors for the various types of glaucoma. A
complete medical history, including current medication and known medicine
intolerance and allergies, is essential.
The Literature
There are no publications on history taking in chronic open angle glaucoma.
2. Visual Acuity
Key Question: Is there evidence that the testing of visual acuity alone or along
with other tests, either using Snellen’s chart or any other clinically used vision
chart, can contribute to the detection of chronic open angle glaucoma?
Evidence Synthesis: There is no evidence synthesis report on this question.
The Guidelines
ICO –recommends the testing of VA but does not give a reason (A: III)
AAO – Does not include VA in eight elements on which to focus in the
examination of glaucoma patients and glaucoma suspects
Singapore - The visual acuity and IOP are neither specific nor sensitive enough
in themselves to be effective diagnostic or screening tools (B: IIa)
RCOphth – no mention
Asia Pacific – VA is not mentioned but gross visual function is included in
history
European Glaucoma Society – no mention
Finland – refers to visual acuity as a basic examination
AOA – 1.Corrected and uncorrected distance or near vision acuity, or both, should
be measured as one indicator of the integrity of the central vision system. 2.
Various forms of treatment for glaucoma as well as advanced stages of the disease
can affect visual acuity.
The Literature
Stamper RL
The effect of glaucoma on central visual function.
Trans Am Ophthalmol Soc.1984;82:792-826.
Stamper argued that there are enough clinical and experimental reports to suggest
that central visual acuity is affected early in glaucoma but that these changes are
not picked up by the Snellen’s Chart. His hypothesis was not taken further in the
medical literature and at best it can be classified as Level 3 taking into account
that he has reviewed the literature and some others were of his opinion.
Level of Evidence – 3
Recommendation - D
3. Colour Vision
Key Question
Is there evidence that the examination of colour vision is useful in the detection of
chronic open angle glaucoma?
Evidence Synthesis – There is no evidence synthesis report on this question.
The Guidelines
Only AOA refers to the examination of colour vision and concludes that it is of no
value
The Literature
Adams AJ, Rodic R, Husted R, Stamper R
Spectral sensitivity and colour discrimination changes in glaucoma and glaucomasuspect patients.
Invest Ophthalmol Vis Sci. 1982 Oct;23(4):516-24
Adams et al reviewed the literature and found studies suggesting that colour vision
changes may occur early in the course of glaucoma and may precede visual field
loss. Glaucoma suspects, having raised intraocular pressure and no diagnostic
optic nerve head or visual field changes, may also have colour vision loss. They
conducted their own case control study and concluded that minor modifications of
the Farnsworth D-15 panel test produce highly significant differentiation of
glaucoma and glaucoma-suspect patients from age-matched normal groups.
Level of Evidence - 3
Heron G, Erskine NA, Farquharson E, Moore AT, White H.
Colour vision screening in glaucoma: the Tritan Album and other simple tests.
Ophthalmic Physiol Opt. 1994 Jul;14(3):233-8. (level IV evidence; case control
study)
The authors used simple colour vision tests for the detection of the Type III colour
vision deficiency in glaucoma and ocular hypertension. Best results were obtained
from a combination of City University Colour Vision Test and AO HRR plate test
scores. No acquired tritan defects were identified by the Farnsworth F2 plate.
Level of Evidence – 3
Recommendation - D
4. Contrast Sensitivity
Key Question: Is there evidence that the examination of contrast sensitivity is
useful in the detection of chronic open angle glaucoma?
Evidence Synthesis: There is no evidence synthesis report on this question.
The Guidelines
Only AOA refers to the examination of contrast sensitivity and concludes that it is
of no value.
The Literature
Stamper RL
The effect of glaucoma on central visual function.
Trans Am Ophthalmol Soc.1984;82:792-826.
Stamper, and others quoted by him, have demonstrated the reduction of temporal
contrast sensitivity in patients with glaucoma and some glaucoma suspects. He
concluded that despite the useful information that they provide, tests for contrast
sensitivity functions are not quite ready for routine clinical use.
Level of Evidence – 3
Wilensky JT, Hawkins A
Comparison of contrast sensitivity, visual acuity, and Humphrey visual field
testing in patients with glaucoma.
Trans Am Ophthalmol Soc. 2001;99:213-7; discussion 217-8.
Patients with a diagnosis of glaucoma, glaucoma suspect, or ocular hypertension
whose visual acuity was 20/40 (logMAR = 0.3) or better were included in the
study. Visual acuity was measured using the Lighthouse visual acuity charts.
Contrast sensitivity was measured using the Pell-Robson (PR) chart. The mean
depression (MD) score from the most recent Humphrey visual field was used to
quantify the visual field defect. The PR contrast sensitivity score correlated more
strongly with the MD of the visual field (r = .589, P < .001) than did the logMAR
visual acuity (r = .193, P = .035). When just the eyes with open-angle glaucoma
were considered, the correlation was even greater for the PR score (r = .638). In
ocular hypertensive eyes, the correlations to PR and logMAR were not that
different (r = .394 for PR, r = .303 for logMAR). The authors speculated that this
decrease in contrast sensitivity in glaucoma patients may account for their
complaints of poor vision despite normal or near normal visual acuity.
Level of Evidence - 3
Hawkins AS, Szlyk JP, Ardickas Z, Alexander KR, Wilensky JT
Comparison of contrast sensitivity, visual acuity, and Humphrey visual field
testing in patients with glaucoma.
J Glaucoma. 2003 Apr;12(2):134-8.
This prospective cross sectional case series was undertaken to investigate the
phenomenon that despite their normal or near-normal Snellen visual acuity,
patients with glaucoma often complain of "poor" vision. Using the methodology
of the previous study, the authors evaluated 250 eyes, subjects with a diagnosis of
glaucoma, suspected glaucoma, or ocular hypertension. The authors found that
reduced contrast sensitivity is significantly correlated with visual field losses in
patients with glaucoma and a visual acuity of 20/40 or better which supported the
previous conclusion that, compared with visual acuity, the disease process
preferentially affects contrast sensitivity.
Level of Evidence – 3
Recommendation – C
5. Visual Performance
This section refers to the overall visual performance of the glaucoma patient in
daily life and not in clinical tests. There are several studies on the quality of life of
the glaucoma patient but they will not be included, and only those that describe
visual performance elements that may aid in detection will be presented.
Evidence Synthesis – There is no evidence synthesis report on this question
The Guidelines
ICO – recommends ssessment of impact of visual function on daily living and
activities (A:III)
AAO – recommends assessment of impact of visual function on daily living and
activities (A:III)
Singapore – no mention
RCOphth – no mention
Asia Pacific – recommends including visual symptoms of blurring and discomfort
(Posner-Schlossman and pigment dispersion syndromes), glare and coloured rings
around lights from corneal oedema, poor light dark adaptation and difficulty
tracing fast moving objects (tennis or golf ball) history taking.
European Glaucoma Society – no mention
Finland – no mention
AOA – Recommends examination for relative afferent papillary defect
Nelson P, Aspinall P, O’Brien C.
Patients’ perception of visual impairment in glaucoma: a pilot study.
Br J Ophthalmol 1999; 83:546–552
In this study, 63 glaucoma patients completed a questionnaire containing 62
questions covering 10 broad aspects of daily life activities using a five point
answer scale. Patients were classified into three groups as having mild, moderate,
and severe field loss on the basis of the perimetric results. The relation between a
measure of the severity of visual field loss and subjective visual disability in the
three groups was examined. The most frequently reported problems were grouped
into the following four categories: outdoor mobility, glare and lighting conditions
and activities demanding functional peripheral vision, household tasks, and
personal care. With increasing severity of binocular visual field loss there was an
increase in the number of self reported visual problems. A loss of confidence in
performing some routine daily tasks tended to precede self reported specific visual
disabilities. The factor “glare and lighting and activities demanding functional
peripheral vision” was found to have a significant relation with a measure of
visual field loss.
Level of Evidence – 3
Jampel HD.
Glaucoma patients' assessment of their visual function and quality of life.
Trans Am Ophthalmol Soc. 2001;99:301-17
In this study, 237 glaucoma patients evaluated their vision using 2 utility tests, and
2 quality-of-life instruments. Their results were compared to clinical tests of their
vision and to persons with normal vision and to blind persons. On a scale of 0
(blind) to 100 (ideal), subjects with normal vision rated their vision higher (90 +/8.0) than did glaucoma subjects and suspects (75.7 +/- 17.6) and "blind" subjects
(15.6 +/- 15.3), P = .001.
Level of Evidence - 3
Recommendation - D
6. Relative Afferent Pupillary Defect
Key Question: Is there evidence that the examination of the relative afferent
papillary defect is useful in the detection of chronic open angle glaucoma?
Evidence Synthesis: There is no evidence synthesis report on this question.
The Guidelines
ICO – Recommends examination for relative afferent papillary defect (B-II)
AAO – Recommends examination for relative afferent pupillary defect (B-II)
Singapore – Informs that 1. there will be a relative afferent pupillary defect
(RAPD) if asymmetrical involvement. 2. patients with chronic glaucoma
may have no symptoms or signs, apart from abnormal pupil light reflexes
and optic disc cupping
RCOphth – no mention
Asia Pacific – no mention
European Glaucoma Society – no mention
Finland – no mention
AOA – Recommends examination for relative afferent papillary defect
The Literature
Brown et al studied 27 consecutive patients with glaucoma who had either a
relative afferent pupillary defect (RAPD) or asymmetric optic nerve cupping
without an RAPD. Every patient with a visual field asymmetry and a sensitivity
difference of 13% or greater had an RAPD. The authors concluded that the
presence of an RAPD indicates that a threshold of asymmetric optic nerve damage
has been exceeded.
Level of Evidence – 3
Recommendation – D
7. Water Drinking Test
Key Question: Is there evidence that the water drinking test is useful in the
detection of chronic open angle glaucoma?
Evidence synthesis: There is not evidence synthesis report on this question
The guidelines
Water drinking is only described in the European Glaucoma Society guidelines.
The literature
Roth JA
Inadequate diagnostic value of the water-drinking test.
Br J Ophthalmol. 1974 Jan;58(1):55-61
The author reviewed the literature on the water drinking test and found that many
investigators have evaluated it and considered it to be a reliable method of
diagnosing chronic simple glaucoma. Some authors found it reliable with
applanation rather than with indentation tonometry. Most authors have agreed that
a rise in intraocular pressure (IOP) of 6 mm. Hg is suggestive of the presence of
chronic simple glaucoma, but opinions have varied as to what is to be considered
as a truly pathological rise. The author then did his own investigation by
examining the notes of patients who have had the water drinking test and
applanation tonometry in the Institute of Ophthalmology, London. Using the 6
mmHg criterion, he found that the highest proportion of positive tests was
obtained in eyes with ocular hypertension (82%), the next in glaucoma suspects
(74%), followed by glaucoma (52%), and then by normal individuals (22%). The
author concluded that the water-drinking test cannot be used to separate the four
categories described and is therefore of very limited value as a provocative test for
chronic simple glaucoma.
Level of Evidence – 3
Rasmussen KE, Jorgensen HA.
Diagnostic value of the water-drinking test in early detection of simple glaucoma.
Acta Ophthalmol (Copenh). 1976 Apr;54(2 p):160-6
A series of 64 patients (119 eyes) subjected 10 years previously to water
provocative tests on a suspicion of simple glaucoma were followed up. At that
time the intraocular tension exceeded 20 mmHg, but there were no optic disc
changes and no visual field defects. Setting a rise of 8 mmHg as the lower limit,
the water provocative test ten years previously had been positive in 31 eyes. Nine
of these developed glaucomatous visual field defects despite treatment (29 per
cent). The test had been negative in 88 eyes. Of these, 21 (24 per cent) developed
glaucomatous visual field defects. The water-drinking test was negative in 70 per
cent of the eyes which subsequently developed visual field defects and negative in
75 per cent of those in which no defects developed. Thus the test was neither of
diagnostic nor of prognostic value. This indicated that a negative water-drinking
test gave a false security. An alteration of the lower limit of a tension rise does not
render the water provocative test any more useful.
Level of Evidence – 2
Recommendation – C
Susanna R Jr, Vessani RM, Sakata L, Zacarias LC, Hatanaka M.
The relation between intraocular pressure peak in the water drinking test and
visual field progression in glaucoma.
Br J Ophthalmol. 2005 Oct;89(10):1298-301
This is a retrospective analysis of 76 eyes of 76 open angle glaucoma patients
followed for a mean period of 26.0 (SD 13.8) months. Patients were submitted to
the water drinking test at the beginning of the follow up period. The results of the
water drinking test were compared between glaucomatous eyes with and without
visual field progression. A significant difference of 1.9 (SD 0.6) mm Hg (p =
0.001, analysis of covariance; 95% CI 0.8 to 3.0) was observed between
glaucomatous eyes that showed visual field deterioration and glaucomatous eyes
that did not progress. A significant difference of 16.8% (SD 4.6%) in the mean
percentage of IOP variation was also observed between the two groups (p<0.001,
analysis of covariance; 95% CI 7.7 to 26.0). The authors suggested that the water
drinking test is a low cost and feasible test and may reflect one of the important
and common disturbances to steady state IOP during a common activity of daily
living: drinking water. The also suggested that the emphasis on the value of the
water drinking test should be changed. It may be useful as a complementary exam
to check IOP control in the clinical practice. The concluded that the peak and
percentage of IOP variation of this test should be considered when analysing risk
factors for glaucoma progression and that future randomised controlled
longitudinal studies may give a better evaluation of this possibility.
Level of Evidence – 2
Recommendation – C
8. Central Corneal Thickness
Key Questions
Question 1: For which patients is pachymetry appropriate?
Question 2: What is the optimal way to measure CCT and when?
Question 3: What, if any, correction factor should be applied on measuring IOP?
Evidence Synthesis
Behki R,. Damji KF, Crichton A for the CCT workshop participants
Canadian perspectives in glaucoma management: the role of central corneal
thickness
Can J Ophthalmol. 2007; 42 (1): 66-74.
The above report is based on evidence from a review of glaucoma literature, a
Canadian consensus development workshop and the personal clinical experience
of the participating Canadian Ophthalmologists.
Question 1
For which patients is pachymetry appropriate?
CCT should be measured in glaucoma suspects and considered in those with
definite glaucoma. Measuring CCT consistently provides additional knowledge
regarding IOP accuracy as well as possible prognosis and future treatment effect.
Published evidence regarding the value of CCT for prognostic information is
strong in the case of patients with ocular hypertension but considerably weaker in
patients with established glaucoma. It is important to educate patients regarding
their CCT and its implications, although this will need to be tailored given a
potentially short encounter time and the complexity of the discussion. Significant
deviations of CCT from the appropriate population mean, may change our strategy
in management of these patients (i.e., ocular hypertensive patients with very thick
corneas, or very thin corneas in patients with borderline pressures).
Question 2
What is the optimal way to measure CCT and when?
1. Ultrasonic pachymetry by a trained individual
2. At least 2 hours after patient awakening.
3. Record time of day.
4. Consider repeating at least once on a different visit
5. Beware of confounding factors (e.g., contact lenses, photorefractive
keratectomy, Fuchs’ endothelial dystrophy)
Question 3
What, if any, correction factor should be applied?
1. There was no universally agreed-upon nomogram that the group could
recommend that could be applied as a correction factor. Nevertheless, currently
available nomograms may be helpful in estimating the amount that the pressure
reading is over or under the actual IOP.
2. Always communicate measured IOP rather than corrected IOP
The Guidelines
ICO – Recommends measurement (A:II)
AAO – Measurement of central corneal thickness aids the interpretation of IOP
measurement results and stratification of patient risk. (A:II)
Singapore – pachymetry may be employed according to the clinical context
RCOphth - Thinner than average central corneal thickness is a risk factor for the
conversion of OHT to POAG
Asia Pacific – Thicker corneas are associated with artificially elevated IOP
measurements, thinner corneas with artificially depressed IOP measurements:
apply correction 1-3 mm HG/40μ deviation from 525 μ on applanation tonometry.
European Glaucoma Society – Central corneal thickness measurements are
valuable 1) only to correct for Goldman applanation IOP measurement, 2) if
interpreted within the general variability of tonometry readings, 3) especially
when treatment of ocular hypertension is being considered, 4) when clinical
findings do not match with IOP and 5) after corneal refractive surgery
Finland – explanation to its relationship to IOP
AOA - The general consensus seems to be that measuring CCT by pachymetry
is only necessary in rare circumstances. The effect of CCT variation on
applanation tonometry readings does not appear sufficient to influence treatment
decisions.
9. Measurement of Intraocular Pressure
Key Questions
Question 1 - Is there evidence of any factors that need to be taken into account in
a clinical situation for determining the final IOP reading?
Question 2 - Is there evidence on the reliability of the different types of tonometer
in the measurement of intraocular pressure?
Question 1 - Is there evidence of any factors that need to be taken into
account in a clinical situation for determining the final IOP reading?
Evidence Synthesis: There is no evidence synthesis report on this question
The Guidelines
ICO – 1) IOP should be measured (A:I). 2) Time of day recorded because of
diurnal variation (B:III)
AAO – 1) Intraocular pressure is measured in each eye (A:I), preferably using a
contact applanation method (typically a Goldmann tonometer) before gonioscopy
or dilation of the pupil.(A:III). 2) Time of day should be recorded because of
diurnal variation. (B:III), (C:III) in a glaucoma suspect. The assessment may
benefit from determining diurnal IOP fluctuations, either on the same day or on
different days, which may be indicated when disc damage exceeds the amount
expected based on a single IOP measurement.
Singpore - People suspected of glaucoma should undergo measurement by
Goldmann applanation tonometer (Grade C, Level IV)
RCOphth - IOPs recorded during the process of management should be
considered to be measured samples of a true IOP that may be fluctuating. Before
attributing too much significance to a single reading ("high" or "low"), the
following factors should be considered:-i) measurement error which may be
equipment and/or patient/operator related ii) diurnal variation
Asia Pacific gives a detailed review of all the factors that need to be taken into
account as follows
Circadian Cycle: The IOP follows a circadian cycle, often with a peak in the
morning and a trough in the evening. The normal diurnal variation is 3-6 mm Hg
Central Corneal Thickness: Thicker corneas are associated with artificially
elevated IOP measurements, thinner corneas with artificially depressed IOP
measurements: apply correction 1-3 mm HG/40μ deviation from 525 μ.
Blood Pressure: IOP is systemically associated with systemic blood pressure,
particularly systolic blood pressure.
Age: In Caucasians, each decade after 40 years of age is associated with an
approximate increase of 1 mmHg in IOP. Systemic hypertension may confound
this relationship.
Exercise: Exercise may increase (e.g. yoga head-down positions) or reduce (by
dehydration and/or acidosis) IOP by 3-6 mmHg
Lifestyle: Large volume rapid fluid intake increases IOP, while alcohol and
marijuana depress it.
Posture: Horizontal or head down position increases IOP.
European Glaucoma Society - Corneal characteristics that can affect IOP
measurements are corneal thickness, curvature and hydration. A tight collar or tie,
Valsalva manoeuvre, holding breath, a lid speculum or squeezing the lids can all
falsely increase the IOP reading.
Finland - A single value of IOP does not give a true picture of the diurnal
variation of IOP. The least progression of the disease has been found in glaucoma
patients whose diurnal pressure variation was modest. Intraocular pressure varies
at different times of the day and the highest values are usually measured in the
morning. Small central corneal thickness value may result in low IOP readings
and large value in high IOP readings. A meta-analysis reported that a 10%
difference in corneal thickness results in approximately 3.4mmHg difference in
IOP.
AOA – 1) Measurement of the IOP should precede papillary dilation and
gonioscopy. 2) The time of day at examination should be recorded. 3) Multiple
measurements in each eye (serial tonometry) at various times of the day may help
to evaluate diurnal variability.4) Attention should be directed toward differences
between the IOPs
of the two eyes and changes in pressure over time.
The Literature
Most of the literature on this topic has been presented with the risk factors for
glaucoma. There will therefore be no further discussion of the literature for this
topic
Question 2 - Is there evidence on the reliability of the different types of
tonometer in the measurement of intraocular pressure?
There are many types of tonometers and they are broadly differentiated by the
physical principle by which they measure the IOP, portability and contact with the
cornea. The Goldmann applanation tonometer is currently the gold standard. As
for the rest, there is no evidence synthesis report on their reliability and the
literature search did not return a general review.
Publications comparing the different types of tonometers are rife, but results are
inconsistent and there is no uniformity between the populations or the
combination of tonometers compared.
This section therefore will only review the different types of tonometers
The Tonometers
The Goldmann applanation tonometer (Haag Streit AG, Bern, Switzerland) is
currently the most widely used tonometer by ophthalmologists in their consulting
rooms, and is considered to be the gold standard for measuring intraocular
pressure (IOP).The Goldmann tonometer, however, cannot be used for bedridden
patients, for younger children, in the operating room, and in other situations
outside the consulting room. Although there is a portable Goldmann applanation
tonometer (Perkins; Clement-Clarke Inc., Columbus, OH, USA), it is not always
suitable. Other portable tonometers have been developed, and the Tonopen
(Mentor, Santa Barbara, CA, USA) is the oldest of these. It is a handheld device
that uses the same physical principle as the Goldmann applanation tonometer. An
earlier version of the Tonopen was the Oculab Tonopen and the latest version is
the Tonopen XL.1
For half a century the Schiotz tonometer, an indentation tonometer, was the
standard for measuring IOP and it is still useful for measurements at the bedside
and in the operating room. Measurement errors can be introduced by the
instrument and the observer. Variations in the curvature and thickness of the
cornea and ocular rigidity affect the measurement. With indentation tonometry a
relatively large amount of fluid is displaced, which increases the pressure by an
amount that varies with the scleral rigidity. If the rigidity is high, the pressure may
be overestimated; and if low, underestimated. Indentation of the eye by the
plunger pushes fluid out of the eye, so repeat measurements over a short period of
time lower the pressure, which also reduces measurement reliability.2
There are several models of the air puff non contact tonometer, which uses air to
flatten the cornea. These include the Topcon CT-10, Reichert XPERT and NCT II
and Keeler PULSAIR.3
The TGDc-01 (Ryazan State Instrument-making Enterprise, Ryazan,
Russia), is a portable tonometer. It has been designed to measure the
IOP through the eyelids, without anaesthesia or contact with the cornea. The
movement pattern of a small rod falling freely onto the eyelid surface is measured.
Individual measurements are displayed digitally. Three measurements are advised
in the interest of reliability.1
The ICARE tonometer (TA01; Tiolat Oy, Helsinki, Finland) uses the impact
rebound principle. A small probe is propelled against the cornea, impacts with it
and rebounds from the eye. The movement of the probe induces a small induction
current enabling the impact duration to be measured. It is a handheld tonometer
with single-use probes that can be used without anaesthesia. Individual
measurements are digitally displayed, and after six consecutive measurements the
average result is given as well as a variability measure.1
The dynamic contour tonometer (DCT, Pascal tonometer,
SwissMicrotechnology AG, Port, Switzerland) was recently introduced as a new
method of intraocular pressure measurement, supposedly independent of corneal
properties. It is a slit lamp-mounted device for contact tonometry that is based
upon corneal contact without corneal applanation. Dynamic contour tonometry
(DCT) claims independence of corneal properties by measuring IOP without
causing considerable corneal deformation. A contour matched pressure-sensing tip
is applied to the corneal surface with a small constant force and allows direct
transcorneal IOP measurement. Diastolic IOP, ocular pulse amplitude, and the
quality of data (Q1–5) are reported on a digital display.4
The Proview phosphene tonometer is based on the principle that pressure
applied to the sclera generates a self perceptible visual phenomenon, known as a
phosphene spot. The threshold pressure for creating a phosphene spot may provide
an indication of IOP. The tip of the tonometer is pressed against the closed eyelid,
and the pressure is read from the scale on the side of the device when the patient
detects the phosphene. The Proview method has several theoretical advantages
over the Goldmann method. It is relatively simple to use without extensive
training, and it does not require anesthetic drops, fluorescein, or expensive
equipment. As it does not require contact with the cornea, it may be useful for
patients with corneal abnormalities that may interfere with accurate pressure
measurements. By not applanating the cornea, the Proview may also circumvent
inaccuracies related to corneal thickness.5
The ocular response analyser (ORA) determines corneal biomechanical
properties using an applied force–- displacement relationship. An air jet similar to
that used in traditional air-puff tonometers generates force/ pressure on the cornea.
To distinguish between corneal biomechanical properties and IOP, the ORA uses
a method that eliminates the potential interference between the two factors in a
single measurement. Pairs of measurements are used because a measurement of a
single parameter cannot determine the independent corneal properties and IOP. 5
The ocular blood flow (OBF) pneumotonometer (OBF Laboratories,
Malmesbury, Wiltshire, England), now being marketed as the Ocular Blood Flow
Analyser (Paradigm Medical Industries, Salt Lake City, UT), is a relatively new
method of tonometry. The pneumotonometer also measures pulsatile ocular blood
flow and hence can achieve two purposes in one measurement.6
1. Liane H. van der Jagt and Nomdo M. Jansonius. Three portable tonometers, the
TGDc-01, the ICARE and the Tonopen XL, compared with each other and with
Goldmann applanation tonometry Ophthal. Physiol. Opt. 2005 25: 429–435
2. Ravin JG, Higginbotham EJ. Are we there yet? Celebrating the centennial of
the Schiotz tonometer. Arch Ophthalmol. 2006 Sep;124(9):1337-8.
3. Brencher HL, Kohl P, Reinke AR, Yolton RL. Clinical comparison of air-puff
and Goldmann tonometers. J Am Optom Assoc. 1991 May;62(5):395-402
4. Schneider E, Grehn F Intraocular pressure measurement-comparison of
dynamic contour tonometry and goldmann applanation tonometry. J Glaucoma.
2006 Feb;15(1):2-6.
5. Herndon LW. Measuring intraocular pressure-adjustments for corneal thickness
and new technologies. Current Opinion in Ophthalmology 2006, 17:115–119
6. Bhan A, Bhargava J, Vernon SA, Armstrong S, Bhan K, Tong L, Sung V.
Repeatability of ocular blood flow pneumotonometry. Ophthalmology. 2003
Aug;110(8):1551-4.
The Guidelines
Asia Pacific - Use Goldmann style applanation tonometer and Tonopen if not
available. Pneumotonometer and Schiötz tonometer are less than ideal. The
guidelines also describe in detail 1) how to perform Goldmann tonometry, 2)
factors affecting measured IOP (as above), 3) measurement errors associated with
Goldmann applanation tonometry, 4) how to test calibration of a Goldmann
tonometer and 5) tonometry mires.
European Glaucoma Society – Recommendations on methods of tonometry are
as follows 1) air puff tonometry is not recommended for evaluation of patients
with glaucoma. 2) pneumatonometry is useful in eyes with scarred, oedematous
and irregular corneae and 3) the Tonopen is useful in patients with corneal
oedema or irregularities.
Finland - 1) the non contact tonometer may give different readings to the
applanation tonometer. 2) the Schiötz tonometer is best suited to for the diagnosis
of closed angle glaucoma.
10. Gonioscopy
Key Question – Is there evidence that goniscopy is essential for the detection
of chronic open angle glaucoma?
Evidence Synthesis – there is no evidence synthesis report on this question.
The Guidelines
ICO – initial evaluation includes gonioscopy (A:III)
AAO - The diagnosis of POAG requires careful evaluation of the anteriorchamber angle to exclude angle closure or secondary causes of IOP elevation,
such as angle recession, pigment dispersion, peripheral anterior synechiae, angle
neovascularization, and trabecular precipitates.(A:III).
Singapore – gonioscopy demonstrates an open angle which is a sign of POAG.
RCOphth - The starting point is a detailed baseline assessment which under
normal circumstances would include an examination of the anterior segment with
a slit-lamp, at least one IOP measurement, and gonioscopy.
Asia Pacific – 1) a gonioscope that allows indentation gonioscopy is included in
the minimal acceptable resources for examination. 2) gonioscopy is mandatory for
every glaucoma suspect, irrespective of whether the suspicion is based on a raised
IOP, optic disc or visual fields finding.
European Glaucoma Society – gonioscopy is an essential part of the evaluation
of all glaucoma patients.
Finland - The diagnosis of glaucoma is based on the examination of the optic
nerve
head, nerve fibre layer, visual fields, IOP level and gonioscopy.
AOA - Careful evaluation of the anterior chamber angle is essential for
differentiating between open angle and closed angle glaucomas, and for
distinguishing primary glaucoma from many secondary glaucomas. It may be
valuable to evaluate the angle both before and after dilation of the pupil. Standard
classification and drawing at initial visit are suggested.
The Literature
The literature on gonioscopy is old and was mostly written to describe the
procedure and the different classification systems. Following this, there has been
very little mention of gonioscopy in the literature.
11. Pupil Dilatation
Key Questions
Question 1 – is there evidence that pupil dilatation is essential in the assessment
of the glaucoma patient?
Question 2 – is there evidence that pupil dilatation in the glaucoma patient is
safe?
Question 1 – is there evidence that pupil dilatation is essential in the
assessment of the glaucoma patient?
Evidence Synthesis – there is no evidence synthesis report on this question
The Guidelines
ICO – the initial evaluation to include evaluation of the fundus (through a dilated
pupil whenever feasible) (A:III)
AAO – 1) the preferred technique for optic nerve head and retinal nerve fibre
layer evaluation involves magnified stereoscopic visualization (as with the slitlamp biomicroscope) preferably through dilated pupil. (A:III) Inability to dilate
(or the reason not to dilate) the pupil should be documented (B:III) and 2)
examination of the fundus, through a dilated pupil whenever feasible, includes a
search for other abnormalities that might account for visual field defects (e.g.,
optic nerve pallor, tilted disc, disc drusen, optic nerve pits, optic nerve hypoplasia,
neurological disease, macular degeneration, and other retinal disease). (A:III)
Singapore – no mention
RCOphth - A careful stereoscopic disc assessment through the dilated pupil and
drawing completes the pre-treatment picture.
Asia Pacific – Stereoscopic view for optic disc examination is best when the pupil
is dilated and this is recommended when safe.
European Glaucoma Society – the pupil should be dilated whenever possible to
facilitate the examination of the optic nerve head and the nerve fibre layer.
Finland – no mention
AOA – 1) optic nerve and nerve fibre layer assessment should be through a
dilated pupil if clinically appropriate. 2) The ability to diagnose PEX can be
increased by 10−20 percent when biomicroscopy is performed through a dilated
pupil as pigment may be dispersed from the pigment epithelium of the iris near the
pupil, and the peripheral granular zone on the anterior surface of the lens in PEX
is best viewed through a dilated pupil.
Evidence Level – 4
Recommendation - D
Question 2 – Is there evidence that dilatation of the glaucoma patient is safe?
Evidence Synthesis
Pandit RJ, Taylor R.
Mydriasis and glaucoma: exploding the myth. A systematic review.
Diabet Med. 2000 Oct;17(10):693-9.
In this systematic review, the authors investigated the risk of inducing acute
glaucoma following mydriasis. They identified 28 studies published between 1933
and 1999 and categorised them into those on the general population, on people
with chronic glaucoma, on eyes following iridectomy for acute glaucoma and on
untreated ‘high risk’ fellow eyes. They found that the risk of inducing acute
glaucoma following mydriasis with tropicamide alone is close to zero, no case
being identified and the risk with long-acting (atropine or homatropine) or
combined agents (tropicamide plus phenylephrine) is between 1 in 3380 and 1 in
20 000. The presence of chronic glaucoma constitutes no additional risk. They
concluded that mydriasis with tropicamide alone is safe even in people with
chronic glaucoma.
Level of Evidence - 1
Hancox J, Murdoch I, Parmar D
Changes in intraocular pressure following diagnostic mydriasis with
cyclopentolate 1%.
Eye. 2002 Sep;16(5):562-6.
In this study the IOP of 83 cataract, 87 medical retinal and 100 glaucoma patients
was
measured with Goldmann applanation tonometry before and 45 minutes after
dilatation with 1% cyclopentolate. An approximately normal distribution of
change in IOP following dilatation was seen in all three groups (mean change 0.4
mmHg (95% CI 0.1–0.8)). Two glaucoma patients with open angles developed a
clinically important (>10 mmHg) sustained rise in IOP requiring treatment. In
medical retina and cataract patients, sustained clinically important rises in
intraocular pressure following dilation seem rarer. The authors recommended that
the IOP be rechecked after dilation in glaucoma patients with significantly
damaged optic nerve heads.
Level of Evidence – 3
Recommendation – B (In view of the findings of the Hancox et al study)
12. Optic Disc Examination
Key Questions
Question 1 - Is there evidence of optic nerve head changes that are
pathognomonic of chronic open angle glaucoma?
Question 2 – Is there evidence that the new technologies for analysis of the optic
nerve head contribute to the detection of glaucoma?
Question 1 - Is there evidence of optic nerve head changes that are
pathognomonic of chronic open angle glaucoma?
Evidence Synthesis – there is no evidence synthesis report on this question.
The Guidelines
ICO – no mention
AAO – 1) diffuse thinning, focal narrowing, or notching of the optic disc rim,
especially at the inferior or superior poles, 2) disc rim hemorrhages or 3) optic
disc neural rim asymmetry of the two eyes consistent with loss of neural tissue. 4)
visible structural alterations of the optic nerve head and development of
peripapillary choroidal atrophy frequently occur before visual field defects can be
detected. Careful study of the optic disc neural rim for small hemorrhages is
important, since these hemorrhages can precede visual field loss and further optic
nerve damage.
Singapore - The hallmark of glaucoma is thinning and damage to the neuroretinal
rim of the optic disc, resulting in the following appearances 1) increased cup-disc
ratio (C/D), 2) focal thinning or notching of the neuro-retinal rim and 3) optic disc
haemorrhage.
RCOphth – Because the concept of that POAG only occurs with pressures over
21 mmHg is incorrect, increasing emphasis has been placed upon the
morphological changes occurring at the optic nerve head and retinal nerve fibre
layer.
Asia Pacific - 1) Features of the neuroretinal rim that would raise suspicion that
glaucomatous damage has already occurred including notching or the rim
(especially to the disc margin), haemorrhage crossing the rim, undercutting of the
rim, asymmetry of rim width between the eyes in the absence of asymmetry of
disc size or an abnormally thin rim in one or two sectors. An approximate rule is
that a vertical cup disc ratio of >0.7 is strongly or loss of rim to the disc margin
anywhere outside the temporal sector is suggestive of glaucoma, 2) The ISNT rule
is that normally the thickest to the thinnest parts of the neuroretinal rim of the
optic disc are Inferior Superior Nasal Temporal. Any variation from this may help
detect glaucomatous damage
European Glaucoma Society – 1) Glaucoma is characterised by progressive
thinning of the neuroretinal rim. The loss of rim may take the form of diffuse
thinning, localised notching or both in combination. Thinning of the rim, while
occurring in all disc sectors, is generally greatest at the inferior and superior poles
leading to a loss of the physiological rim shape so that the inferotemporal rim is
no longer the thickest. The optic cup often enlarges in all directions, but usually
the enlargement occurs predominantly in the vertical direction as a result of rim
loss at the poles. 2) Since the prevalence of disc haemorrhages is low in the
normal population, their presence is very likely to be pathological. 3) Because
some degree of parapapillary atrophy is present in many normal eyes, a large area
of atrophy should be regarded as an extra clue to local vascular damage associated
with glaucoma. 4) An early sign of acquired rim thinning is a circumlinear vessel
becoming bared. A difference in cup/disc ratio between eyes with equal overall
optic disc size is suggestive of tissue loss and therefore is highly suspicious of
acquired damage. 5) The rim/disc ratio is the fractional decimal value obtained
dividing the rim thickness by the disc diameter. The closer its value is to 1, the
better the disc appearance.
Finland – 1) Structural abnormalities in the optic nerve head precede visual field
ones. 2) The preperimetric glaucoma is defined by normal visual field in spite of
structural
abnormalities in the optic disc and the nerve fibre layer. 3) A large cup in a large
disc raises suspicions of glaucoma even if the IOP is not elevated. A small optic
nerve head is more insidious because early disc abnormalities may go unnoticed.
4) A splinter haemorrhage in the nerve head may foretell and precede the
glaucomatous damage and its progression both in the optic disc, nerve fibre layer
and visual fields. 5) Peripapillary atrophy is more prevalent in glaucoma subjects
than in the healthy population but its significance for the aetiology and
progression of disease abnormalities is unclear and its presence cannot be used to
distinguish between healthy and glaucomatous subjects.
AOA 2) Features of the neuroretinal rim that would raise suspicion that
glaucomatous damage has already occurred including notching or the rim
(especially to the disc margin), haemorrhage crossing the rim, undercutting of the
rim, asymmetry of rim width between the eyes in the absence of asymmetry of
disc size or an abnormally thin rim in one or two sectors. An approximate rule is
that a vertical cup disc ratio of >0.7 is strongly or loss of rim to the disc margin
anywhere outside the temporal sector is suggestive of glaucoma, 3) The ISNT rule
is that normally the thickest to the thinnest parts of the neuroretinal rim of the
optic disc are Inferior Superior Nasal Temporal. Any variation from this may help
detect glaucomatous damage
The Literature – The fundamental optic disc changes in chronic open angle
glaucoma were described in the seventies and eighties. Since that time, there has
been isolated publications confirming or quantifying these changes and
differentiating between glaucomatous and non glaucomatous optic disc cupping.
No recent comprehensive review of this question was found in the peer reviewed
literature although it has been reviewed in several textbooks.
Question 2 – Is there evidence that the new technologies for analysis of the
optic nerve head contribute to the detection of glaucoma?
Evidence Synthesis
Committee on Ophthalmic Procedures Assessment
American Academy of Ophthalmology.
Optic nerve head and retinal nerve fiber layer analysis.
Ophthalmology. 1999 Jul;106(7):1414-24.
This report reviewed the literature on the Rodenstock Optic Nerve Head Analyser
(no longer manufactured), the Heidelberg Retina Tomograph (HRT), Scanning
Laser Polarimetry (SLP; example of which is GDx) and Optical Coherence
Tomography (OCT) for their advantages, disadvantages, sensitivity, specificity,
accuracy, sources of error and reproducibility in the detection of glaucoma. Only
the Rodenstoch Optic Nerve Head Analyser and the Heidelberg Retina
Tomograph were evaluated in relation to the optic nerve head. HRT has been
shown to have high reproducibility, but relatively poor correlation with an
experienced observer’s assessment of optic disc parameters. It has the advantage
of obtaining images through an undilated pupil and through cataracts, although
one study showed reduced reproducibility in patients using pilocarpine. Several
studies have also shown that the standard optic disc parameters, such as the cup to
disc ratio, rim area, and cup area, are no longer adequate to distinguish subtle
findings in the optic nerve head of glaucomatous eyes. First, there is overlap
between what is considered normal optic nerve and early glaucomatous optic
neuropathy when only looking at these parameters. Second, focal loss of rim area
may well be missed when only these parameters are considered. This problem was
addressed by incorporating other parameters into the HRT software. One of these
parameters is the cup shape measure. In clinical studies it has shown some
promise in correlating with automated perimetry parameters. However, this
correlation was not adequate to detect early to moderate glaucoma damage as
measured by achromatic automated perimetry. The Heidelberg Retina Tomograph
sensitivity and specificity to detect glaucomatous optic neuropathy were variable,
largely due to the study design of selecting patients with variable degrees of visual
field loss as well as to the statistical methods employed in the study. Despite the
seemingly high sensitivity and specificity, this should be in interpreted with
caution given the low prevalence of glaucoma. However, HRT may be useful in
monitoring patients with glaucoma because of its high reproducibility.
Level of Evidence - 1
The Literature
The following two reviews were published five years later and their conclusions
did not differ much with those of the assessment report above.
Stein DM, Wollstein G, Schuman JS
Imaging in glaucoma.
Ophthalmol Clin North Am. 2004 Mar;17(1):33-52
Burgoyne CF.
Image analysis of optic nerve disease.
Eye. 2004 Nov;18(11):1207-13.
The following report was commissioned by the NHS R&D Health Technology
Assessment Programme. The work was based at the Manchester Royal Eye
Hospital.
Kwartz AJ, Henson DB, Harper RA, Spencer AF, McLeod D
The effectiveness of the Heidelberg Retina Tomograph and laser diagnostic
glaucoma scanning system (GDx) in detecting and monitoring glaucoma
Health Technology Assessment 2005; Vol. 9: No. 46
The objectives of this study were 1) to compare the diagnostic accuracy of optic
nerve head tomography (HRT) and scanning laser polarimetry (GDx) for
identifying patients with glaucomatous visual field loss, 2) to investigate the
applicability of the instruments in an unselected population of hospital patients, 3)
to measure the length of time required for a full examination and 4) to calculate
between- and within-observer variability in HRT and GDx measurements.
The study examined two groups of patients cross-sectionally (150 glaucoma
patients and 100 normal individuals) and two groups longitudinally (240 high risk
eyes and 75 glaucoma patients). Each examination session involved image capture
with the HRT and GDx and assessment with the 24-2 full threshold program of
the HFA. Patients within the cross sectional groups underwent a single
examination, whereas patients in the longitudinal groups were examined 6
monthly for an average of 3.5 years. From the cross-sectional group, the
maximum sensitivities of the HRT and GDx were 59% and 45%, respectively (at
95% specificity). From the two longitudinal cohorts, the level of agreement
between the three instruments for identification of the development and
deterioration of POAG was low. The applicability of the techniques was 80%
(HRT), 88% (GDx) and 98% (HFA). The length of time to perform a full
examination with each instrument was 12.3, 11.8 and 28.3 minutes, respectively.
Agreement of HRT and GDx parameters between and within observers was
largely good. The research concluded that there is little agreement between HFA,
HRT and GDx. The techniques are amenable to use in the clinical environment
but no single examination has sufficient diagnostic precision to be used in
isolation. In order to provide a full investigation of the glaucoma patient or
suspect, the clinician needs a stereoscopic examination of the ONH and RNFL
with true colour representation. This examination is necessary in order to detect
changes such as RNFL haemorrhages or pallor of the neuro-retinal rim, which are
significant findings in glaucoma. Such alterations cannot easily be detected with
the HRT or GDx. The findings of the glaucoma imaging study suggest that,
although the HRT and GDx provide good-quality digital images, their data may
contribute little to a patient’s clinical diagnosis but would add significantly to the
cost of their assessment.
The Guidelines
ICO – Key elements of the initial examination are 1) evaluation of optic nerve
head with magnified stereoscopic visualization (A:III) and 2) documentation of
the optic disc morphology, best performed by colour stereophotography or
computer-based image analysis (A:II)
AAO – 1) There is evidence that glaucomatous changes detected by analysis of
the optic nerve head may precede changes detected by standard automated
perimetry. 2) The preferred technique for optic nerve head involves magnified
stereoscopic visualization (as with the slit-lamp biomicroscope) preferably
through a dilated pupil. (A:III}. 3) Direct ophthalmoscopy is useful in some cases
to complement magnified stereoscopic visualization, providing more
comprehensive information of optic nerve detail due to the greater magnification
of the direct ophthalmoscope. 4) Color stereophotography or computer-based
image analysis of the optic nerve head (A:II} are recommended for
documentations. In the absence of these technologies, a nonstereoscopic
photograph or a detailed drawing of the optic nerve head should be recorded but
these are less desirable alternatives to stereophotography or computer-based
imaging. (A:III)
Singapore – Optic nerve head imaging is an ancillary test which may be
employed.
RCOphth - Baseline appearance of the optic disc may be obtained by various
means including stereophotography or computerised digital imaging.
Asia Pacific – 1) The disc size can be measured using a thin slit lamp beam, the
small size spot of the direct ophthalmoscope, photography with an overlay grid or
imaging. .2) Qualitative methods for assessment of optic disc are direct
ophthalmoscopy, indirect slit lamp ophthalmoscopy, disc photograph and
simultaneous stereophotography. Quantitative methods are disc photography with
digitalisation, stereo disc photography with optic disc analysis, confocal laser
scanning ophthalmoscopy, laser polarimetry and optical coherence tomography.
European Glaucoma Society – Lists imaging technology but no evaluation
Finland – 1) Description of the optic disc, estimation of cup/disc ratio or a
drawing are not as accurate as optic disc photography or imaging. However,
optimum usage of images requires profound experience. 2) High technology
instruments (the
Heidelberg retina tomograph, retinal nerve fibre analyser and optical coherence
tomography), developed for nerve fibre layer and optic disc imaging and
measurements, are not yet ready for routine glaucoma diagnostics, although due to
their sensitivity and specificity, some may be used for the follow-up of glaucoma
AOA – 1) Examination of the ON requires procedures that provide stereoscopic
visualization with adequate magnification, through a dilated pupil if clinically
appropriate. Use of a biomicroscope with an ancillary lens is the preferred
procedure for . A 60 D lens, a 66 D lens, or a contact fundus lens will enable the
best stereopsis. Evaluation of the ON includes ruling out other potential causes. 2)
Despite the large ON cups in eyes that eventually develop glaucoma, the clinical
finding of a 0.6 cup-to- disc ratio has only about a 60 percent (41%−77%)
sensitivity for predicting which cases of OH will convert to the disease. There is
no cutoff value for cup-to-disc ratio that changes this conclusion. Determining the
cup-to-disc ratio by direct ophthalmoscopy is even less precise, due to
intraobserver and interobserver variability. The evidence suggests even greater
variability in assessment of the notching or width of the neuroretinal rim.
Topography of the optic nerve and configuration of the neuroretinal rim may be
more sensitive and specific than the cup-to-disc ratio in the detection of glaucoma.
3) Stereoscopic fundus photography is useful for evaluating the ON because it
reduces observer variability in assessment of the cup-to-disc ratio. 3) Users of
confocal scanning laser tomography (CSLT) have concentrated on the early
detection of patients with glaucoma. The most beneficial application of this
technology may be in the detection and monitoring of subtle changes in ON tissue
over time. Because of significant physiological variation of the optic nerve head
within the normal population, even with an ideal imaging system, it is very
difficult to identify early glaucoma accurately in a single session. Although with
CSLT there is a tendency to overestimate the neuroretinal rim and to
underestimate the cup-to-disc ratio, several recent studies have shown that the
parameters generated by this technology are adequate for discrimination between
normal optic nerve heads and those of patients with ocular hypertension and early
glaucoma. CSLT has a sensitivity of 89 % and a specificity of 84 % for
differentiating between subjects with early glaucomatous VF defects and normal
eyes.
13. Examination of the Nerve Fibre Layer
Key Questions
Question 1 - Is there evidence that examination of the nerve fibre layer
contributes to the detection of glaucoma?
Question 2 – Is there evidence that the new technologies for examination of the
nerve fibre layer contribute to the detection of glaucoma?
Question 1 - Is there evidence that examination of the nerve fibre layer
contributes to the detection of glaucoma?
Evidence Synthesis – there is no evidence synthesis report on this question.
The Guidelines
ICO – A key element in the initial evaluation is examination of the retinal nerve
fibre layer with magnified stereoscopic visualization (A:III)
AAO - 1) Retinal nerve fibre layer evaluation (A III), 2) There is evidence that
glaucomatous changes detected with optic disc and retinal nerve fibre layer
analysis may precede changes detected by standard automated perimetry. 3)
Examination of the retinal nerve fibre layer provides valuable structural
information about glaucomatous optic nerve damage. 4) The preferred technique
for optic nerve head and retinal nerve fibre layer evaluation involves magnified
stereoscopic visualization (as with the slit-lamp biomicroscope) preferably
through a dilated pupil. (A III). 5) Red-free illumination may aid in evaluating the
retinal nerve fibre layer. Inability to dilate (or the reason not to dilate) the pupil
should be documented. (B III). Colour stereophotography or computer-based
image analysis of the optic nerve head and retinal nerve fibre layer are the best
currently available methods to document optic disc morphology and should be
performed. In the absence of these technologies, a nonstereoscopic photograph or
a detailed drawing of the optic nerve head should be recorded but these are less
desirable alternatives to stereophotography or computer-based imaging.
Singapore – Nerve fibre layer imaging is an ancillary test which may be
employed
RCOphth – 1) Because the concept of that POAG only occurs with pressures
over 21 mmHg is incorrect, increasing emphasis has been placed upon the
morphological changes occurring at the optic nerve head and retinal nerve fibre
layer. 2) Retinal nerve fibre layer defect in the absence of morphometric optic
nerve head changes is a risk factor for the conversion of ocular hypertension to
POAG.
Asia Pacific – 1) Record whether nerve fibre layer is visible and assess for wedge
or slit defects
European Glaucoma Society – 1) The thickness of the nerve fibre layer depends
on the disc area, age and stage of the glaucomatous damge.2) It was shown that
vertical polar sectors were thicker than polar and temporal ones.3) It was shown
the retinal nerve fibre layer height in normal was thicker than in glaucomatous
subjects. 4) Localised loss of nerve fibre layer is more common in normal pressure
glaucoma.5) A feature of the primary open angle glaucoma suspect is that the
visual field and/or optic nerve and/or nerve fibre layer are normal or suspicious
with at least one being suspicious.
Finland – 1) The diagnosis of glaucoma is based on the examination of the optic
nerve head. 2) Structural abnormalities in the optic disc and retinal nerve fibre
layer precede visual field abnormalities. 3) Most cases of glaucoma – including
the preperimetric glaucoma – may be diagnosed when the optic disc and the nerve
fibre layer are examined in addition to visual field examination. 2) The
preperimetric glaucoma is defined by normal visual field in spite of structural
abnormalities in the optic disc and the nerve fibre layer. 4) Examination of the
nerve fibre layer facilitates and supports the glaucoma diagnostics based on the
optic disc and visual field evaluation, in particular with unusually small or large
optic discs. It is possible to observe glaucomatous abnormalities in the nerve fibre
layer before abnormalities can be detected in the optic disc and/or the visual
field.5) A quality criteria for the self evaluation of glaucoma care is the proportion
of patients who have had photography of the nerve fibre layer.
AOA – 1) The procedure for evaluating the integrity of the NFL is similar to that
described for the ON. The NFL is best visualized using stereo photographic
techniques with red-free illumination and high-resolution black and white film.
Serial NFL examination is more sensitive than colour ON evaluation in detecting
the conversion of eyes from OH to POAG. In one study, a minority of the eyes
(about 20%) with OH that converted to glaucoma over a 5-year period showed
changes in the ON, while about 50 percent showed developing or worsening
atrophy of the NFL. In another study, 60 percent of eyes with OH that converted
to POAG had NFL defects at least 6 years before VF loss, and 88 percent had
NFL defects at the time of the initial visual loss. Significant advances have
occurred in techniques for assessing the NFL in the detection and progression of
glaucoma. Studies have investigated the capabilities of scanning laser polarimetry,
optical coherence tomography, and scanning laser ophthalmoscopy in
distinguishing normal and OH eyes from those with POAG, as well as the
reproducibility of results obtained with these instruments. Although the study
results are encouraging with respect to accurate measurement of NFL thickness,
whether these instruments have the sensitivity and specificity to detect the onset
and the progression of glaucomatous damage remains to be determined. The
correlations between VF indices and peripapillary NFL thickness have been weak,
and the distribution of parameters measured by these techniques in normal eyes
overlaps measurements made in eyes with OH or both OH and POAG, thereby
reducing the sensitivity and the specificity of these tests.
Question 2 – Is there evidence that the new technologies for examination of
the nerve fibre layer contribute to the detection of glaucoma?
Evidence Synthesis
Committee on Ophthalmic Procedures Assessment
American Academy of Ophthalmology.
Optic nerve head and retinal nerve fiber layer analysis.
Ophthalmology. 1999 Jul;106(7):1414-24.
This report reviewed the literature on the Rodenstock Optic Nerve Head Analyser
(no longer manufactured), the Heidelberg Retina Tomograph (HRT), Scanning
Laser Polarimetry (SLP; example of which is GDx) and Optical Coherence
Tomography (OCT) for their advantages, disadvantages, sensitivity, specificity,
accuracy, sources of error and reproducibility in the detection of glaucoma. The
HRT, SLP and OCT were evaluated in relation to the nerve fibre layer.
Scanning laser polarimetry and optic coherence tomography were both shown to
have good reproducibility and resolution as well as good correlation with
histological measurements of the NFL thickness. Both have the advantage of
obtaining measurements directly without a reference plane as well as of obtaining
measurements independent of magnification and optical resolution of the human
eye.
However, the scanning laser polarimetry retardation measurements may be
influenced by all of the polarizing structures of the eye, including the cornea, the
lens, peripapillary atrophy, and chorioretinal scars. Optical coherence tomography
requires pupillary dilation and may be influenced by certain types of cataract, such
as posterior subcapsular and cortical opacities. The sensitivity and specificity are
variable in clinical studies and are due largely to the use of different frequency
distributions of what is normal, the definition of abnormal by visual field defects
as measured by automated perimetry and statistical methods of analysis.
Histopathologic studies and clinical studies have demonstrated tremendous
variability of RNFL thickness in normal eyes. Obviously, this will limit the
detection of early glaucoma using this measurement alone despite the reported
high sensitivity and specificity.
The Literature
Bagga H, Greenfield DS.
Retinal nerve fiber layer assessment using scanning laser polarimetry.
Int Ophthalmol Clin. 2004 Spring;44(2):29-42. Review.
This is a report which reviewed the historical development of GDx, its
technological principles, reproducibility, sensitivity, specificity, capacity to detect
glaucomatous progression, strengths and limitations. The authors found that
numerous studies have reported high discriminating power for separating normal
persons from those with glaucoma, and good agreement with other structural
technologies and that recent advances in scanning laser polarimetry provide a
means to obtain objective, quantitative, and reproducible structural measurements
of peripapillary RNFL thickness. Using SLP with fixed corneal compensation,
sensitivity and specificity values approximate 70% to 80% depending upon
sample size, definition of glaucoma, and severity of glaucomatous damage.
Methods for change detection exist but have not been prospectively validated in
large populations. As with perimetry, it is not recommended that isolated clinical
decisions be based solely upon ocular imaging results. Clinical correlation should
be performed and treatment recommendations should be individualized.
Stein DM, Wollstein G, Schuman JS
Imaging in glaucoma.
Ophthalmol Clin North Am. 2004 Mar;17(1):33-52
This review outlines confocal scanning laser ophthalmoscopy (CSLO), scanning
laser polarimetry (SLP), optical coherence tomography (OCT), and the retinal
thickness analyzer (RTA). It reviews their fundamentals, reproducibility, sources
of error or variability, ability to distinguish normal from glaucomatous eyes,
strengths and limitations. The authors concluded that although these
measurements have been found to provide useful data for glaucoma detection in
various regions of the posterior segment, further studies are needed to evaluate the
utility of these technologies for preperimetric glaucoma detection and for
monitoring glaucoma progression over an extended period.
See also the health technology assessment above by Kwartz , Henson, Harper,
Spencer and McLeod, 2005
The Guidelines
ICO – no mention
AAO – no mention
Singapore – no mention
RCOphth – no mention
Asia Pacific – no mention
European Glaucoma Society
Imaging devices may aid clinical management. These include confocal scanning
laser ophthalmosocopy (e.g. HRT), scanning laser polarimetry (e.g. GDx), optical
coherence tomography (e.g. OCT) and retinal thickness analyser (e.g.RTA). It
must be emphasised that the process of categorising patients by means of imaging
device measurement is not the same as diagnosis. Diagnosis must integrate all the
other available information including clinical assessment of the ONH and the
RNFL, visual field and risk factors including IOP, age and family history. In the
future, with greater clinical information being provided by optic disc
measurement, and the cost of the instruments declining, the clinical use of these
devices is likely to expand.
Finland
High technology instruments (the Heidelberg retina tomograph, retinalnerve fibre
analyser and optical coherence tomography), developed for nerve fibre layer and
optic disc imaging and measurements, are not yet ready for routine glaucoma
diagnostics. Due to their sensitivity and specificity, some instruments may be used
for the follow-up of glaucoma
AOA
Confocal scanning laser polarimetry, optical coherence tomography, confocal
scanning laser ophthalmoscopy can be used in the assessment of the nerve fibre
layer in the initial evaluation of glaucoma.
14. Visual Field Testing
Key Question
Is there evidence that examination of the visual field by any method of
perimetry if useful in the diagnosis of glaucoma?
Evidence Synthesis
Delgado MF, Nguyen NT, Cox TA, Singh K, Lee DA, Dueker DK, Fechtner RD,
Juzych MS, Lin SC, Netland PA, Pastor SA, Schuman JS, Samples JR; American
Academy of Ophthalmology. Ophthalmic Technology Assessment Committee
2001-2002 Glaucoma Panel.
Automated perimetry: a report by the American Academy of Ophthalmology.
Ophthalmology. 2002 Dec;109(12):2362-74.
Early detection of visual field defects is an important goal of current practice if
glaucoma is to be diagnosed and treated in its earliest stages. Standard threshold
automated perimetry involves determining the minimum luminance necessary for
the patient to detect the presentation of a static white light stimulus of constant
size in various locations of the visual field. Because standard threshold automated
perimetry uses a static achromatic stimulus, it is thought to nonselectively invoke
the two major groups of ganglion cells of the optic nerve, as they are now
commonly classified. Since there is considerable overlap in the receptive fields of
retinal ganglion cells, a test with a nonselective stimulus may not be highly
sensitive for the earliest loss of retinal ganglion cells due to the considerable
redundancy in the coverage of a given location in the retina. Therefore, unless the
damage is very localised, standard threshold automated perimetry may not detect
visual field loss until the optic nerve has already suffered considerable damage.
One goal of current research is to develop quicker tests and evaluations that
maintain or improve diagnostic accuracy and reproducibility to help detect
glaucoma at an early stage and recognize slight disease progression. The ideal test
would be rapid, inexpensive, applicable to the majority of the population, easy to
use and highly sensitive and specific. This assessment describes four automated
perimetry tests: blue-yellow perimetry, or short wavelength automated perimetry
(SWAP); frequency doubling technology perimetry. (FDT); high-pass resolution
perimetry (HPRP); and motion automated perimetry (MAP). The assessment also
describes two static perimetry algorithms, the Swedish interactive threshold
algorithm (SITA), and SITA fast.
Short Wavelength Automated Perimetry (SWAP)
Glaucomatous optic nerve damage may be associated with an acquired color
vision deficit in the blue-yellow spectrum and/or red-green spectrum.7 It is
proposed that blue-yellow perimetry, or SWAP, is more effective than whitewhite standard threshold automated perimetry in detecting early visual field loss.
Frequency Doubling Technology Perimetry (FDT)
The frequency doubling phenomenon, or “frequencydoubling illusion,” is a
phenomenonwhere the alternating light and dark bars appear to have twice the
actual number of bars when shown at low spatial frequency and high temporal
frequency counterface flicker Frequency doubling technology perimetry is a
contrast threshold test with a more complex target than standard threshold
automated perimetry.
High-Pass Resolution Perimetry (HPRP)
High-pass resolution perimetry is thought to test the parvocellular system
selectively. HPRP uses a photopic background on a cathode ray tube where ringshaped stimuli of various sizes are presented at different locations in the visual
field. Instead of using differential light sensitivity, this test measures resolution
threshold, the ability of the retina to resolve varying target sizes. Threshold is
detected by 14 different ring-sized targets, which measure 50 locations within the
central 30°. The central-most 5° and the vicinity of the blindspot cannot be
quantified because of monitor limitations and because the targets subtend too
large an angle (which is also why this test cannot measure a small isolated
scotoma). Another substantial limitation is the inability to standardise between
cathode ray tube monitors.
Motion Automated Perimetry (MAP)
Motion information travels through the magnocellular ganglion cells pathway, and
the perception of motion is an essential visual function. Glaucoma patients have
shown defects in motion perception as well as prolonged reaction times, and less
precise localization of motion stimuli. Based on these findings, researchers have
developed perimetric techniques to detect motion sensitivity defects. There are as
many types of MAP protocols as there are different groups of researchers.
Swedish Interactive Threshold Algorithm (SITA)
Compared with newer strategies, conventional full threshold strategies use shorter
stimulus steps and more reversals, producing longer testing staircase sequences, to
establish threshold at each test locus. This results in longer tests, which are
difficult to use in the clinical setting because they cause patient fatigue and
compromise the reliability of the test. The Swedish interactive threshold algorithm
(SITA) is a strategy designed to reduce testing time substantially without
decreasing the quality of test results.
Swedish Interactive Threshold Algorithm Fast (SITA fast)
SITA fast reduces testing time with a test accuracy similar to FastPac
This assessment addressed the following question: Can the automated
perimetry tests and algorithms described detect glaucomatous damage or
detect the progression of glaucoma?
Blue-yellow perimetry, or SWAP, showed early detectionof glaucomatous loss
(based on Level II evidence). This is a long and challenging test for patients to
undergo. New developments on a SITA version of SWAP are being researched,
and it is possible that further algorithm refinements similar to SITA may allow
SWAP to be faster and thus more practical. Frequency doubling technology
perimetry significantly reduces testing time and is not as affected by blur and
pupil size as standard threshold automated perimetry. Studies also showed
reduced intratest and intertest variability when compared to standard threshold
automated perimetry. High sensitivity and specificity for FDT compared to
standard threshold automated perimetry was demonstrated in one Level I study for
detecting early, moderate, and advanced glaucomatous loss, although a Level II
study found FDT less effective for advanced glaucoma. It may be that FDT
perimetry is currently most useful as a screening tool, although further advances
in this technology may allow it to become appropriate for long-term follow-up of
patients. High-pass resolution perimetry can be sensitive to media opacities and
blur. One Level I study demonstrated its ability to detect early glaucomatous loss
and progression. It is associated with a shorter testing time and increased patient
comfort relative to standard threshold automated perimetry, but prospective
studies are needed to define its role in the clinical setting. Motion perception
defects/deficits can be a strong predictor of visual field loss. Motion automated
perimetry is useful for detecting early glaucomatous visual loss (Level I
evidence), but its use has not yet been popularized. Studies on SITA show
significant reduction in testing time (50%) without affecting diagnostic accuracy,
making it a more patient-friendly test. It is associated with a greater sensitivity and
reproducibility and less intertest variability when compared with standard full
threshold testing (Level II evidence). It is important to establish a new baseline
when patients are switched from the standard threshold automated perimetry
algorithm to SITA. While this may be cumbersome in the short term, the switch to
SITA is generally preferred by most patients. In principle, the different algorithms
(SITA standard, SITA fast) can be applied on all different stimulus modalities.
Not all combinations of algorithm and test are commercially available today.
The Literature
Henson Perimeter
Henson DB, Bryson H
Clinical results with the Henson-Hamblin CFS2000.
Documenta Ophthalmologica Proceedings Series 49
Seventh International Visual Field Symposium, Amsterdam, September 1986
EL Greve and A Heijl (Eds)
Henson-Hamblin CFS2000 is a computerised central visual field analyser which
contains a screening programme that tests 26 retinal locations and a full
programme which tests 132 stimulus locations. It also contains two quantification
systems; the first gives an estimate of the likelihood that a given response is
normal while the other gives a measure of the visual field survival (100-percent
field loss). It uses a multiple stimulus suprathreshold static technique. The
stimulus intensity is gradient adapted and increases by 0.8 log units from the
centre of the visual field to an eccentricity of 25 degrees. In this study, 94 eyes
from patients suspected of having glaucoma were examined. The screening
programme was found to have a sensitivity of 90.5% and a specificity of 88.4%.
The following studies have been published about alternative methods of
visual field examination
Confrontation
Johnson LN, Baloh FG.
The accuracy of confrontation visual field test in comparison with automated
perimetry.
J Natl Med Assoc. 1991 Oct;83(10):895-8.
In this study, the accuracy of confrontation visual field testing was determined for
512 visual fields using automated static perimetry as the reference standard. The
assessment was mainly for neurological field defects but confrontation testing was
fairly insensitive (20%sensitivity) for detecting arcuate scotoma. The specificity
of confrontation testing was high at 93.4%. The high positive predictive value
(72.6%) and negative predictive value (75.7%) would indicate that visual field
defects identified during confrontation testing are often true visual field defects.
However, the many limitations of confrontation testing should be remembered,
particularly its low sensitivity for detecting visual field loss associated with
glaucoma.
Shahinfar S, Johnson LN, Madsen RW.
Confrontation visual field loss as a function of decibel sensitivity loss on
automated static perimetry. Implications on the accuracy of confrontation visual
field testing.
Ophthalmology. 1995 Jun;102(6):872-7.
This is a study to evaluate the accuracy of confrontation visual field testing with
regard to the density of the visual field defect and its location in the peripheral
visual field. Seventy-two patients with a variety of neurologic and ophthalmologic
conditions underwent confrontation visual field testing full-threshold Humphrey
automated static perimetry C24-2 or C30-2and. Confrontation visual field testing
yielded an overall sensitivity for detecting an abnormal visual field of 63%, when
sensitivity of confrontation testing rested on the detection of just one abnormal
quadrant. The sensitivity of confrontation testing was 51% for arcuate scotomas.
The sensitivity of confrontation testing was lower for superior quadrant defects
and higher for inferior quadrant defects. Specificity was 97% and the positive
predictive value was 96%. The authors concluded that confrontation visual field
testing is relatively insensitive unless a moderate to dense defect is present, and as
such is a poor screening test. However, when visual field defects are identified
with confrontation visual field testing, the defects often are real with a high
specificity and positive predictive values.
Pandit RJ, Gales K, Griffiths PG.
Effectiveness of testing visual fields by confrontation.
Lancet. 2001 Oct 20;358(9290):1339-40. Erratum in: Lancet 2001 Nov
24;358(9295):1820.
The authors prospectively compared seven confrontation field tests with fullthreshold automated static perimetry among 138 outpatients in an eye clinic. The
primary outcome was detection of a defect in the visual field. Most confrontation
field tests were insensitive in the identification of field loss. The most sensitive
method was examination of the central 20 degrees visual field with a small red
target (73% [95% CI 63-82]).
Goldmann Perimetry
The limitations of kinetic perimetry in early scotoma detection.
Ophthalmology. 1978 Mar;85(3):287-93.
When tested by Goldmann kinetic perimetry ten patients with glaucomatous optic
disc cupping had no visual field defects, but visual field defects were detected
when tested by threshold static perimetry on the Tubingen perimeter.
Friedman Field Analyser
Hicks BC, Anderson DR.
Quantitation of glaucomatous visual field defects with the Mark II Friedmann
analyzer.
Am J Ophthalmol. 1983 May;95(5):692-700.
In this study, the authors correlated the visual threshold determined kinetically
(Goldmann perimeter) with the static threshold (Friedmann analyzer) in various
parts of the central field. Friedmann working threshold correlated linearly with the
height of the hill of vision represented by the position of the kinetic isopters of the
Goldmann perimeter. The static visual threshold (Friedmann) at a particular
location, whether normal or abnormal, was linearly related to the kinetic visual
threshold (Goldmann) at that location. The depth of all visual field defects was
essentially the same with both instruments. Thus, the Friedmann analyzer
accurately quantitated the central visual field in both the normal and abnormal
regions, and may be advantageous for following the progress of early
glaucomatous defects. For other patients, however, its usefulness may be limited,
because defects outside 25 degrees cannot be documented, the visual field
examination may be lengthy and inefficient when quantitating large defects of
irregular depth and the maximal quantitation of depth with the Friedmann
analyzer is 2.0 log units less than with the Goldmann perimeter near fixation (but
there is progressively less difference for defects further from fixation).
The Guidelines
ICO - Visual field evaluation, preferably by automated static threshold perimetry
is a key element in the initial evaluation of the glaucoma patient (A:III)
AAO - 1) The visual field abnormality considered a valid representation of the
glaucoma patient’s functional status is a visual field damage consistent with
retinal nerve fibre layer damage (nasal step, arcuate field defect, or paracentral
depression in clusters of test sites) and visual field loss in the upper hemifield that
is different compared with the lower hemifield, i.e., across the horizontal midline
(in early/moderate cases). It should be reproducible and other known explanations
for it should be absent. 2) Automated static threshold perimetry is the preferred
technique for evaluating the visual field. (A:III) Careful manual combined kinetic
and static threshold testing is an acceptable alternative when patients cannot
perform automated perimetry reliably or if it is not available. (A:III)Causes of
visual field loss other than glaucomatous optic neuropathy should be sought and
assessed during the history review and physical examination. (A:III) Visual field
testing based on short wavelength automated perimetry and frequency doubling
technology may detect defects earlier than conventional white-on-white perimetry.
It is important to use a consistent examination strategy when visual field testing is
repeated. (A:III).
Singapore – 1) If glaucomatous nerve damage has been sustained perimetry
shows defects that are consistent with nerve fibre layer loss and these include:
temporal island central island in advanced glaucoma, nasal step, paracentral or
arcuate scotomas. 2) Psycho-physical tests (e.g. Short Wavelength Automated
Perimetry, Frequency Doubling Threshold, etc may also be employed depending
on the clinical context.
RCOphth - The discovery that a significant number of the optic nerve fibres can
be damaged before any change is detectable in visual function by standard
automated perimetry (SAP) has lead to the concept of "glaucoma without field
loss" or “pre-perimetric glaucoma”. However other psychophysical tests such as
frequency doubled perimetry (FDP) and blue on yellow perimetry (SWAP) have
consistently shown that defects in visual function are present before any defect
can be detected by SAP. In this condition (usually with coexistent raised IOP)
there is deemed to be unequivocal
evidence of glaucomatous damage to the optic nerve head +/- the nerve fibre
layer. Clearly, for some patients, there is a grey area between OHT and "glaucoma
without field loss.
Asia Pacific – 1) Users should read and be familiar with the perimeter manual. 2)
The guidelines include an appendix on how to optimise patient performance in
subjective perimetry. 3) Characteristics of glaucomatous visual field defects are
that they are asymmetrical across the horizontal midline, located in the midperiphery in early and moderate cases, reproducible, not attributable to other
pathology, clustered in neighbouring test points (localised) and the defect should
correlate with the appearance of the optic disc and neighbourhood.
European Glaucoma Society – 1) In the absence of retinal or neurological
disease affecting the visual field, loss is considered significant when there is an
abnormal Glaucoma Hemifield Test, confirmed on two consecutive tests, or 3
abnormal points confirmed on two consecutive tests, with p<5% probability of
being normal, one of which should have p<1%, all being not contiguous with the
blind spot, CPSD (corrected pattern standard deviation) <5% if the visual field is
otherwise normal, confirmed on two consecutive tests. 2) Any defect or suspected
defect must be confirmed by repeated testing.3) the guidelines discuss in detail the
sources of error, the duties of the perimeter user, assessing the test results,
including an explanation of the global indices, and the different grading systems
for field defects. 4) Conventional techniques for visual field testing are Humphrey
Perimeter 24-2 or 30-2, Octopus 32, Octopus program G1, SITA Standard and
Fast for Humphrey and TOP for Octopus. Non conventional techniques are SWAP
(Short Wavelength Automated Perimetry), FDT (frequency doubling technology)
and HRP (High Pass Resolution Perimetry).
Finland – 1) If the diagnosis of glaucoma is defined by visual field examination
methods, the clinical significance of a single abnormal visual field is small. 2) In
early glaucoma the visual field abnormalities are detected earlier with static
automated perimetry than with kinetic visual field examination. 3) Blue-on-yellow
perimetry may detect visual field abnormalities earlier and identify them as larger
in size than traditional white-on-white perimetry. 4) Humphrey SITA standard and
Octopus Dynamic are recommended are recommended for diagnosis and follow
up.
AOA – 1) Measurement of threshold levels in areas of the visual field likely to be
affected by glaucomatous damage of the optic nerve should be made by perimetry
through a pupil of adequate size. The results of perimetry should be compared
with the reference values from an age-matched control population and evaluated
with respect to the probability of abnormal (glaucomatous) findings. The clinician
should consider factors that can influence interpretation of the findings, including
the patient's learning curve. 2) FDT perimetry has demonstrated better patient
reliability, less intratest and intertest variability, and results that are comparable to
or better than standard automated perimetry for the detection of glaucoma. It
appears that FDT can facilitate the diagnosis and grading of the extent of
glaucoma. 3) Short-wavelength automated perimetry (SWAP) is useful in
evaluating early or subtle diseases of the optic nerve and retina. A technique with
which to isolate the blue colour (short-wavelength) vision mechanism, SWAP
appears to uncover loss of visual function earlier in the disease process than
traditional white-on-white automated perimetry. SWAP facilitates prediction of
future defects that can eventually be found with white-on-white perimetry. The
visual field defects found with SWAP are larger and progress more rapidly than
those localized with white-on white automated perimetry. 4) An association
between the prevalence of localized SWAP defects and other risk factors is
predictive of the development of glaucoma in patients with OH. The longer
duration of testing and the fluctuation of patient responses that may occur with
SWAP are of clinical concern.