1. health and fitness
2. disease

SFVA
The Dilemma of Early Glaucoma Diagnosis
Andrew B. Mick, OD, FAAO
San Francisco VA Medical Center
UC Berkeley School of Optometry
UCSF Department of Ophthalmology
Kaiser Symposium: February 7, 2009
What is the dilemma of early diagnosis?
We currently can only diagnose glaucoma at the end
of the disease’s progression
There are a significant number of patients in your
practice that have glaucoma too early on to detect!!
As technologies improve, we are going to be able to
diagnose more of these patients.
But is there a time when a diagnosis is so early that
it doesn’t impact the management of the disease?
Dilemma: Do we treat at time of diagnosis?
The number of times we have to make this decision will grow!
Where in the spectrum can we diagnose now?
Future Capabilities?
When we diagnose
Weinreb. Am J Ophthalmol 2004;138(3):458-467.
How much will earlier diagnosis affect your practice?
1
How Big is the Dilemma?
Well, how many conventionally diagnosed glaucoma
patients do your currently have in your practice?
Rates of Glaucoma in Different Ethnic Groups?
African Americans?
Asians?
Hispanics?
Whites?
What is OAG Prevalence?
Prevalence in Different US Ethnic Groups
LALES. Ophthalmology 2004;111(8):1439-1448.
What about in the Asian American Population?
Data is not as good
Average:
2.38%
Law. Int Ophthalmol Clin 2003;43(4):1332003;43(4):133-149
2
Typical Practice of 4000 Adults in Anaheim, California
% Population
White
Population
GLC Prevalence
Total Number
54.0%
2160
1.44%
31
Hispanic 30.0%
1200
4.74%
57
Black
4.0%
160
4.97%
8
Asian
12.0%
480
4.20%
20
Total:
116
Data from “Conventional” Glaucoma Diagnoses!
Screening IOP
Definitive Optic Nerve Change
Screening Visual Fields
What about nonconventional glaucoma diagnoses?
% Population
White
Population
GLC Prevalence
Total Number
54.0%
2160
1.44%
31
Hispanic 30.0%
1200
4.74%
57
Black
4.0%
160
4.97%
8
Asian
12.0%
480
4.2%
20
Total:
116
Huge Underestimation!
3
Where in the continuum is “conventional” diagnosis?
Quigley. Am J Ophthlamol 1983;95:673
We don’t know!
Where in the continuum is “conventional” diagnosis?
Mild Cupping?
Moderate Cupping?
Severe Cupping?
We don’t know!
Quigley. Am J Ophthlamol 1983;95:673
Where in the continuum is “conventional” diagnosis?
How much of the nerve fiber must be lost before first VF loss?
We have an idea of this!!
4
40% of nerve fiber loss before VF loss
50% of nerve fiber loss before mild VF
defects are detected conventionally
Quigley. Arch Ophthalmol 1982;100:1351982;100:135-146.
The Current State of Affairs
Time of Conventional
Diagnosis
Want to Avoid
Wouldn’t it be better to diagnosis at an earlier stage?
What technologies purport to diagnose glaucoma
earlier in the disease spectrum?
Pushing
Diagnosis
Earlier
Frequency Doubling Technology
Short Wavelength Automated Perimetry
5
Short Wavelength Automated Perimetry
Frequency Doubling Technology
Early diffuse loss of nerve fiber layer is difficult to detect
using conventional visual fields
SWS cones and those that detect flicker send signals to
large diameter ganglion cell axons, possibly more
susceptible to pressure, that connect to the specific layers
of the LGN
These ganglion cells are less in number and therefore
have less reserve when loss occurs
109 preperimetric glaucoma patients
20% of prepre-perimetric patients had FDT and
SWAP defects
Greater sensitivities with greater structural
damage
J Glaucoma 2007;16(4):372-83.
62 ocular hypertensives with no standard
white/white visual field defects
Baseline FDT FullFull-Threshold CC-20 and 2424-2
SWAP fields performed and then patients
followed for 3 years
Landers et al. Arch Ophthalmol 2003;121:1705-1710
6
5 patients developed
standard defects during the
study. All 5 had abnormal
SWAP and FDT at baseline
No standard defects
developed in patients
with normal SWAP and
FDT at baseline
Landers et al. Arch Ophthalmol 2003;121:1705-1710
Electrodiagnostics in Glaucoma
Pattern ERG predicted
progression to OAG in a
group of OHT one year before
conversion
IOVS 2006;47(11):4881-7
The mfVEP technique
detected VF defects in a small
percentage of patients with
normal SAP results
J Glaucoma 2006;15(4):321-7
Weinreb. Am J Ophthalmol 2004;138(3):458-467.
FDT and SWAP can detect glaucoma
3-5 years earlier than SAP!
These Technologies are the first to create the Early
Diagnosis Dilemma!
Does it matter in the long term management of your patients?
7
Are there structural techniques that create
more of the Early Diagnosis Dilemma?
Is this glaucomatous?
Are there ways to detect structural changes
prior to clinical observation of the disc?
Current Gold Standard?
Structural Imaging Technologies
In vivo NFL thickness measurements
Ocular Coherence Tomography
Software compares to normative
database
Resolution 88-15 um
Compare to Gold Standard?
Heidelberg Retinal Tomograph
Scanning Laser Polarimetry
79 glaucomatous and 149 normal eyes
Presence of glaucoma tested for 4 techniques:
Stereo Disc Grading
Stratus OCT
HRT II
GDxGDx-Vcc
Sensitivity and Specificity calculated using ROC curves
DeLeonDeLeon-Ortega et al. IOVS 2006;47:33742006;47:3374-3388
8
1 - False Negative Rate
ROC Curves for All 4 Techniques
False Positive Rate
DeLeonDeLeon-Ortega et al. IOVS 2006;47:33742006;47:3374-3388
Final Conclusions:
No significant differences in ROC were found between the
ability of each imaging technique to detect glaucoma
Stereo photographic grading was more sensitive than all
imaging techniques
DeLeonDeLeon-Ortega et al. IOVS 2006;47:33742006;47:3374-3388
233 glaucoma patients and 216 normals
Stereo disc photographs vs. HRT Moorfields Classification
“Subjective optic disc grading outperformed MRC in both
Black and White Subjects”
Ophthalmology 2006;113(12)21442006;113(12)2144-2149
9
Glaucoma Probability Score (GPS) on HRT III vs.
Subjective Disc Assessment in 223 Glaucoma Suspects
Average follow-up 66.3 months
24% converted to VF proven glaucoma during follow-up
Higher GPS scores predicted which eyes would convert
Higher GPS scores were equal to subjective disc
assessment
Alencar. IOVS 2008;49(5):1898-906.
High Resolution Spectral/Fourier Domain OCT
Increased resolution (< 5 um)
Decreased Scan Times
Reichert SOCT Copernicus
Optovue RTVue
Heidelberg Spectralis
Topcon 3-D OCT
Cirrus OCT
Better NFL Visualization with New OCT Technologies
400 A-Scans/Second vs. 24,000 Scans/Second
Stratus OCT
Spectral Domain OCT
Mumcuoqle. Ophthalmology 2008 May;115(5):782-789
10
Will Increased Speed and
Resolution Lead to Better
Diagnostic Ability?
Mumcuoqle. Ophthalmology 2008 May;115(5):782-789
Structural Technologies:
Still have extreme value:
Show overall size of disc
Give objective measurements of NFL and optic
nerve parameters (Progression over time?)
Can “facilitate” the diagnosis of glaucoma
Diagnosing
Glaucoma is common, even by conventional Will
diagnostic
criteria. Far
Far
more patients in your practice have glaucoma
than really
you canmatter?
here
currently detect
Current imaging technologies appear to be on par with stereo photo
photo
grading in detecting glaucoma. Higher resolution may improve
diagnostic ability?
FDT and SWAP appear to be more sensitive than imaging
technologies in detecting glaucoma
Electrodiagnostics are currently not easily clinically applicable
But does the early diagnosis of glaucoma have a
beneficial effect on the longlong-term course of the
disease?
11
How do we resolve the Dilemma?
First things First
What is the GOAL of glaucoma therapy?
To prevent the further loss of retinal ganglion cells
or progression of the visual field?
To have the patient die without glaucoma
having an effect on functional vision!
Other Questions to Answer
We have already said that the goal is preventing vision loss
How many glaucoma patients actually progress to
unacceptable stages?
Can we predict who is going to progress to unacceptable
stages?
Why create a dilemma? What is the harm in just treating all
glaucoma patients at time of diagnosis?
Is glaucoma progression linear, or exponential?
Glaucoma Patients That Develop Visual Impairment
Eye Disease Prevalence Research Group. Arch Ophthalmol 2004;122:477-485.
12
Visually Significant Glaucoma Damage
Blindness
< 20/200 in the better seeing eye
Eye Disease Prevalence Research Group. Arch Ophthalmol 2004;122:477-485.
Visually Significant Glaucoma Damage
Low Vision
< 20/40 in the better seeing eye
Eye Disease Prevalence Research Group. Arch Ophthalmol 2004;122:477-485.
How many glaucoma patients go blind?
Untreated for 10 years
8.8% prevalence of glaucoma in the population
Probability of reaching end-stage disease in at
least one eye was about 16% by AGIS criteria and
was 35% by CIGTS criteria.
Am J Ophthalmol 2002;134(3):399-405.
13
How many glaucoma patients go blind?
295 newly diagnosed glaucoma treated between
1965 and 1980
mean follow-up of 15 years
Probability of Blindness (20/200 or < 200
visual fields) from open angle glaucoma
27% for unilateral blindness
9% for bilateral blindness
Ophthalmology 1998;105(11):2099-2014
How many glaucoma patients go blind?
Sommer: Baltimore Eye Study. N Eng J Med 1991;325:1412-1417
More realistic and current bilateral numbers
~ 4% of White patients
~ 8% of Black patients
Why do so few glaucoma patients go blind?
Most glaucoma is slowly progressive
Most diagnoses occur at later ages
14
Slow Progression: NTGS
In the untreated control group, the average length
of time until there was progression of glaucoma was
1,695 days (4.64 years)
Am J Opthalmol 1998. Oct. 126(4):487126(4):487-497.
Slow Progression: EMGTS
Median time to progression in
untreated controls with OAG
was 48 months (4 years)
Arch Ophthalmol 2002;120:12682002;120:1268-1279
Median time for patients with abnormal SWAP or
FDT fields to develop abnormal standard
white/white fields was 2.25 years.
Landers et al. Arch Ophthalmol 2003;121:1705-1710
15
Why do so few glaucoma patients go blind?
Older Age at Diagnosis
LALES. Ophthalmology 2004;111(8):1439-1448.
Study:
Average Age (Tx
/Control)
(Tx/Control)
EMGTS
68.2/68.0 years
NTGS
66.5/66.3 years
AGIS
65.4 years
CIGTS
61.0 years
Why Does Older Age at Diagnosis Matter?
Life Expectancy
Age
Male
Female
60
Both Sexes
22.3
20.5
23.8
70
15.0
13.5
16.1
80
9.1
8.1
9.7
90
5.1
4.5
5.3
UC Center for Disease Control
So where is the dilemma?:
The goal of therapy is to prevent vision loss
Glaucoma progresses slowly and presents late
A small percentage of patients lose vision
Low percentages, but high overall prevalence!
White: 4% of 1.4 million is 56,000 people!
Black: 8% of 1.0 million is 80,000 people!
16
93 bilaterally blind at MEE
27% blind at diagnosis
Who
goes blind?
75% Goldmann defects at diagnosis
65% prepre-Tx IOP > 30
42% noncompliant
African American Heritage
Grant. Ophthalmology 1982;89(9):991-998.
31 went blind at Washington
Severity of cupping at diagnosis
Severity of VF at diagnosis
Poor compliance
Ophthalmology 2003;110(4):726-733.
NonNon-White ethnicity
56 went blind at Mayo Clinic
Greater VF loss at diagnosis
Greater susceptibilities to IOP
Am J Ophthalmol 2002;133(6):7642002;133(6):764-772.
Making the Dilemma Smaller………………….
No Dilemma at initial visit:
Aggressive disease (High IOP)
Advanced disease at diagnosis
Concern about compliance
Treat
Young age (Most advance ~ 0.5 – 1.0 dB/year)
Dilemma:
Mild disease
Middle/late ages
?????
Early disease at diagnosis
Since you can’t tell who will progress to visual
significance, why not treat them all?
Drugs Have Side Effects!
Lash, skin, and brow changes in my patients
17
Since you can’t tell who will go blind, why not treat
all glaucoma patients?
Alphagan
Hyperemia
Miotics
Accommodative spasm
Brow ache
CAIs
Stinging
Altered taste
Beta Blockers
Shortness of breath
Prostaglandins
Bradycardia
Hyperemia
Sexual dysfunction
Hair/Skin/Iris changes
Depression
Why not treat all glaucoma patients?
All Glaucoma Meds Cause Cataract!
Barbados Eye Disease Study. Ophthalmology 2002;109(7):1303-1308
Blue Mountain Eye Disease Study. Ophthalmology 2006;113(3):417-424
Ocular Hypertension Treatment Trial. Arch Ophthalmol 2002;120:701-713.
Why not treat all glaucoma patients?
Lee et al. Arch Ophthalmol 2006;124:122006;124:12-19.
Economics: Treating glaucoma costs money!
Psychology: Treatment is life long!
18
Resolving the Dilemma?
Risk Factor Assessment
Progression Rate Determination
Talking to your patient!
Resolving the Dilemma:
Ocular Hypertension Treatment Study:
Higher IOP
Larger vertical C/D ratio
Thinner corneas
Larger PSD at baseline
Risk Factor Assessment
Resolving the Dilemma:
Early Manifest Glaucoma Treatment Study:
Higher IOP
Pseudoexfoliation material
Worse baseline MD on visual fields
Presence of disc hemorrhage
Risk Factor Assessment
19
Resolving the Dilemma:
Normal Tension Glaucoma Study:
African American Heritage
Female Sex
Migraine history
Presence of disc hemorrhage
Risk Factor Assessment
The Future: Predictive Models
A prediction model was developed from the OHTS
observation group and was then tested on the
EGPS placebo group
The OHTS model was validated in the EGPS group
Ophthalmology 2007;114(1):10-19
Unfortunately, no validated predictive
models for OAG…………………… yet
Ocular Hypertensive
Estimated 55-yr risk:
69 years of age (3)
Total Points: 14
IOP: 27 mmHg (3)
CCT: 534 um
(3)
C/D: .65
(4)
PSD: 1.9
> 33% risk
(1)
Ophthalmology 2007;114(1):10-19
20
Progression Rate Determination
May be more important than early detection
in the longlong-term management of your patient
Determining progression not a perfect science
Make sure your patient understands they have the disease, just not
being treated for it at this time!
Make sure your patient would rather not just start treatment now!
Arrive upon the decision to monitor as at team.
In Summary:
Glaucoma is an extremely common disorder
New technologies will allow for earlier and earlier diagnosis
Large numbers of patients, but a low % get visual dysfunction
The goal of glaucoma therapy is death with functional vision
Not all glaucoma patients need to be treated
Clinically, the hard part is determining who needs treatment
Treatment indicated for those at risk of visual impairment
Risk factor assessment and determination of
progression rate solve the early diagnosis dilemma
In Summary:
No risk factor calculator or new technology will
replace sound clinical judgment and listening to
patient wishes in determining who needs treatment
Thank You!!
21