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Recurrent corneal
erosion syndrome
48
Rakesh Jayaswal MBChB, FRCS(ED), FRCOphth
Recurrent corneal erosion syndrome (RCES) is a common clinical presentation. Understanding the condition and
when to refer patients is paramount to a successful outcome. This article looks to explain the reasons for RCES
and the challenges of patient management. The current treatment options are improving and varied, and the
benefits of these new interventions will be explained.
06/06/14 CET
Course code: C-36491 | Deadline: July 4, 2014
Learning objectives
To be able to obtain relevant history when presented with cases of recurrent corneal
erosion syndrome (Group 1.1.2)
To be able to use appropriate slit lamp methods to recognise the signs of recurrent
corneal erosion syndrome (Group 3.1.2)
To be able to identify and manage cases of recurrent corneal erosion syndrome
(Group 6.1.4)
Learning objectives
To be able to understand how different methods of slit lamp technique can be used
to identify recurrent corneal erosion syndrome (Group 3.1.2)
To be able to understand the management approach for recurrent corneal erosion
syndrome (Group 8.1.3)
Learning objectives
To be able to understand the treatment and natural course of recurrent corneal erosion syndrome
(Group 1.1.1)
(Knowledge)
syndrome
(Group
1.1.1)
To be able to assess cases of recurrent corneal erosion syndrome using appropriate techniques
(Group
2.1.2)
(Options)
techniques
(Group
2.1.2)
About the author
Rakesh Jayaswal is a consultant ophthalmologist, with specialist training in corneal and anterior segment disease. As the clinical lead for the NHS
corneal service at Queen Alexandra Hospital, Portsmouth, and as founder and a medical director for LaserVision UK, Mr Jayaswal has considerable
clinical experience and expertise in the management of corneal disorders including recurrent corneal erosion syndrome.
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Introduction
49
Figure 1 Slit lamp appearance of active
recurrent erosion showing ragged,
oedematous, disrupted grey epithelium.
Image courtesy of Peter R Laibson21
Figure 2 Broad-beam slit lamp appearance
of anterior basement lines in RCES. Image
courtesy of Peter R Liabson21
Pathophysiology
inflamed mid-stromal keratocytes. Often the
associated trauma that causes RCES originates
from organic material such as fingernails or
plant material, and the theory of a deposition
of a proteinaceous material from such an
injury may explain these findings.
Another theory is based around abnormal
expression of matrix metalloproteinase (MMP)
– a generic name for a group of enzymes
that can degrade part of the structure of the
extracellular matrix. Gelatinase, composed
of matrix metalloproteinase-9 (MMP-9)
and matrix metalloproteinase-2 (MMP-2),
causes degradation of Type IV collagen,
Type VII collagen and laminin – all major
components of a basement membrane. The
tears of patients with a history of traumatic
corneal abrasions and RCE have been shown
to increase MMP-9 and MMP-2 in affected
and fellow eyes as compared with control
eyes.5 Therefore, increased MMP-9 and
MMP-2 expression have been implicated in
the pathogenesis of RCES because the upregulation may lead to basement membrane
degradation and poor epithelial basement
membrane adhesion.
The pathophysiology of RCES is only partially
understood. Normal adhesions for the corneal
epithelium depend on structures known as
attachment complexes, which are composed
of elements from the basal epithelial cell
layer, basement membrane, Bowman’s
layer and corneal stroma. Through electron
microscopy and immunohistochemical
staining methods, these elements are
thought to include hemi-desmosomes,
basal lamina, lamina densa, lamina lucida,
anchoring fibrils, and Types IV and VII
collagen. The presence of abnormal corneal
epithelial basement membrane adherence
to Bowman’s layer, whether by abnormal
adhesion complexes or a reduplication of the
basement membrane itself, is believed to be
the underlying aetiology of recurrent corneal
erosion syndrome.
Recently, the Heidelberg Retina Tomograph
Rostock Cornea Module (HRT II RCM) laser
confocal microscope has been used to
investigate pathologic changes in the
epithelial-Bowman’s membrane adhesion
complex. In patients with (ABMD) and a
history of RCES, the HRT II RCM showed an
abnormal epithelial basement membrane
protruding forward into the corneal
epithelium, the presence of epithelial
microcysts and normal superficial epithelial
cells and stroma.3 In contrast, when HRT II
RCM examined patients with RCES due to
traumatic corneal abrasions, the physiology
of the corneal epithelium did not show these
findings.4 The traumatic corneal erosion
patients exhibited altered epithelial cells,
activated keratocytes in shallow stroma and
Diagnosis
In patients with a history of previous trauma
to the involved eye, episodes of pain on
awakening, and epithelial microcysts, the
diagnosis constitutes minimal clinical
challenge. However, in more subtle cases, the
diagnosis can be more difficult.
After carefully inquiring about trauma
to the affected eye, the clinician should
undertake a detailed slit lamp examination
to find subtle signs of RCES. Several different
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06/06/14 CET
Recurrent corneal erosion syndrome (RCES)
is commonly encountered in clinical practice
and can be a painful, often frightening,
and sometimes incapacitating condition
for many patients. In this syndrome, as the
name implies, corneal epithelial cells erode,
resulting in denuded areas on the corneal
surface. After re-epithelialisation, the process
then recurs when the epithelial cells slough
again at a later time.
The erosions are typically episodic in
nature, with many patients only having mild
symptoms limited to a foreign body sensation
or a vague awareness of the affected eye
between erosions. These symptoms may
be most noticeable in dry, cold or windy
environments. Most erosions occur during
the night or early morning hours and are
often described as an abrupt ‘ripping’ or
‘tearing’ sensation, followed by an immediate
sharp pain, foreign body sensation, epiphora,
photophobia, reduced visual acuity and lid
swelling.
The attacks often vary greatly in pattern
and intensity. Some patients have mild
symptoms every few months or years and
some experience severe, incapacitating,
frequent erosions with symptoms lasting
for a few days at a time. In a small subset of
patients, the epithelial defects may never fully
close, and loose sheets of epithelium slide
over the surface of the eye with each blink.
These patients experience constant pain and
can be extremely distraught.
The unpredictable nature of RCES often
increases patient anxiety, as the knowledge
of the sudden impact an episode can have on
day-to-day life can be extremely disturbing.
It is not uncommon for patients with RCES to
demonstrate signs of depression and anxiety
and some come to fear falling asleep or
awakening, and experience varying degrees
of insomnia.
RCES often occurs due to superficial injury
to the cornea, or may be caused by any
one of the many ophthalmic or systemic
diseases associated with it; these include
anterior basement membrane corneal
dystrophy (ABMD), such as Reiss Bucklers,
lattice, macular, granular and Meesmann’s
dystrophies; bullous keratopathy and
diabetes mellitus.1,2
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50
examination techniques can be helpful in this
scenario. Broad, angled slit beam examination
of both eyes before and after administration
of fluorescein should be performed, as well
as a retro-illumination examination of the
cornea with a dilated pupil to discern the
often subtle signs of basement membrane
dystrophy or areas of previous erosion.
Careful examination not only helps with
diagnosis but also helps identify where to
target treatment. Gentle pressure applied to
the cornea via the eyelid may demonstrate
wrinkling of any loose epithelium. A fine
slit beam examination may reveal subtle
granularity of the stroma, which persists
after restoration of epithelial integrity
(see Figures 1–3).
However, in some patients, even with
the most thorough examination, there may
be a failure to identify any clinical signs.
In such a situation, one should be wary of
labelling these patients as functional or
psychoneurotic, especially if they may be
showing early signs of anxiety or depression.
It is best to advise such patients to return for
examination immediately if the episodic pain
returns.
Treatment
For many years, RCES remained one of the
more frustrating disorders to treat for both
patients and the physician. Today, however,
newer treatment modalities allow for a
rationalised, stepwise approach to manage
patients with RCES, often converting some of
the most distraught individuals to the most
grateful patients in clinical practice.
Topical agents
The initial approach to the medical
management of RCES typically involves
increasing the lubrication of the ocular
surface and maximising the health of the
tear film. A mainstay of medical treatment
optometrytoday
involves the long-term nightly use of
hyperosmotic lubricating ointments. The
rationale for this treatment stems from the
concept of nocturnal relative hypotonicity of
the tear film. At night, with the eyes closed,
tear evaporation is reduced resulting in
lowered concentration of dissolved salts in
the tears. This shift in the osmotic gradients
results in a relative increase in corneal
epithelial oedema and consequent reduction
in epithelial adhesion. The petrolatum vehicle
serves to prevent erosions by keeping the eye
lubricated during the rapid eye movements
stage of sleep (REM) or while opening the eyes
in the morning.
Hyperosmotic eye drops during the daytime
are sometimes added to this approach in an
effort to minimise epithelial oedema during
waking hours, thus allowing reformation of
more normal attachment complexes. These
agents must be used consistently for at least
12 months after the patient’s last erosion,
since it often takes this much time for normal
reformation. Unfortunately, patients frequently
stop the use of these topical agents soon after
the erosions resolve, only to have a recurrence,
which may prolong the time required for the
attachment complexes to reform. Currently
available hyperosmotic ointments include
sodium chloride 5% (Muro-128, Bausch &
Lomb), and sulfacetamide 10% (Bleph-10,
AK-Sulf ).
Some investigators have suggested that
topical corticosteroids combined with oral
doxycycline may help treat recurrent erosions
by the inhibition of MMP-9.6 As mentioned
earlier, metalloproteinases are up-regulated in
the tears of patients with RCES. As MMP-9 and
MMP-2 can degrade Type IV, Type VII collagen
and laminin, doxycycline and steroids, both
metalloproteinase inhibitors, are commonly
used in the treatment of RCES.
In one recent study, patients with RCES
unresponsive to traditional treatment, were
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Figure 3 Slit lamp appearance of eye in
Figure 2 with basement membrane lines
enhanced using fluorescein. Image courtesy
of Peter R Liabson21
placed on oral doxycycline 100mg twicedaily and fluoromethalone (FML) 0.1% four
times daily to inhibit MMP-9.7. FML was
chosen because of its poor penetration
into the cornea, concentrating its effect
in the epithelium. In corneal cultures,
doxycycline produced a 70% reduction in
metalloproteinase-9 activity.7 In addition to
inhibiting MMP-9; doxycycline also improves
meibomian gland dysfunction. A 70% shortterm relapse-free rate, improved subjective
symptoms and a decreased recurrence rate
over 21 months were reported.7-9
Patching and bandage lenses
Bandage contact lenses may be used to treat
acute erosions very effectively, but their use
to prevent future erosions has mixed success.
Silicone hydrogel lenses are often utilised, and
patients are placed on topical antibiotic drops
while an epithelial defect is present due to the
increased risk of microbial keratitis.6,10 When
used long-term, careful discussion about the
risks and signs of infection must occur during
consultation with the patient.
Reflective learning
Having completed this CET exam, consider whether
you feel more confident in your clinical skills – how will
you change the way you practice? How will you use this
information to improve your work for patient benefit?
For patients where medical management
fails to resolve the erosions, several
effective surgical options are available. The
indication for surgical intervention is any
situation in which medical management
fails to improve the symptoms and signs of
erosions, and when the patient’s continued
pain and epithelial defects interfere with
normal activities. The limited risks of surgical
treatment for recalcitrant recurrent erosions
generally override the threat of infection from
erosions, in conjunction with the prospect of
continued patient disability and pain.
Debridement and superficial keratectomy
Historically, debridement and then superficial
keratectomy were the first surgical treatments
for recurrent corneal erosions,11–13 and
these procedures remain in use today.14
Debridement may be useful for removing
a localised area of very loosely adherent
epithelium in a limited number of erosion
patients. This technique requires only a cotton
swab and can be performed at the slit lamp
with topical anaesthesia. The suboptimal
efficacy and limitations of this procedure
derive from the fact that no significant
modifications to enhance epithelial adhesion
are made in Bowman’s layer or other deeper
corneal structures. Studies have shown a
five-year cumulative probability of recurrence
of 44.7%.15
Given the high recurrence rate with
simple mechanical debridement, corneal
surgeons will often undertake a procedure
that will also treat Bowman’s layer to enhance
adhesion. One approach is that of a large
superficial epithelial keratectomy. Various
surgical techniques have been described,
with the aim of lifting the epithelium as a
sheet while preserving Bowman’s layer. The
use of a diamond burr to polish Bowman’s
layer is thought to prevent RCES by both
removing abnormal basement membrane
and by causing a reactive fibrosis to allow
scarring and stronger epithelial adhesion. This
technique is more likely to be successful, with
some studies showing a recurrence rate three
times lower than simple debridement.16
More recently, a technique known as
alcohol delamination has been proposed
to improve the efficacy of debridement
perforations with
this technique, as
well as questions
regarding depth
of penetration and
the possibility of
excessive scarring,
disposable,
specialist
instrumentation
was designed for
Figure 4 Slide of human cadaver eye after stromal puncture. Image
use in corneal
20
courtesy of Rubinfeld RS et al
micropuncture.20
Anterior
stromal puncture (ASP) attempts to improve
in the treatment of recurrent erosions.17
epithelial adherence by inducing scar tissue
Two recent articles investigated the
to form between the epithelium and anterior
use of alcohol delamination in patients
stroma. Although ASP works relatively well in
unresponsive to traditional therapy
increasing irregular epithelium adherence, it
(lubrication, cycloplegia, patching and
17,18
does create scarring (see Figure 5). Therefore,
bandage contact lenses).
Alcohol
it is best used on patients with peripheral
delamination involves epithelial removal
pathology, most likely a post-traumatic RCE
with a 20% alcohol solution in order
patient.
to re-establish a smooth Bowman’s
Anterior stromal puncture is a procedure
membrane surface. Dua et al showed
performed
at the slit lamp under topical
that 66–83% of patients were symptom
anaesthesia.
When discussing this
free after intervention, 75% of patients
procedure with patients, the term epithelial
became symptom free within one
reinforcement may be substituted for stromal
month of treatment and 91–100% of
puncture, as the word ‘puncture’ can be
patients had a favourable response in
frightening for the patient. Treatment within
the decrease of pain symptoms following
18
the pupillary space should be minimised if
treatment. In addition, histopathological
possible. Hyperosmotic ointments should
examination of the epithelial sheets showed
then consistently be used at bedtime for
epithelial separation was at an interface
12 months after stromal puncture while
overlying Bowman’s layer and included a
attachment complexes and other ultraproteinaceous material that had replaced
structural components are reforming to
the anterior basement membrane (ABM).
achieve maximal epithelial adhesion.
The authors considered the proteinaceous
A single anterior stromal puncture
material probably represents a degraded
procedure
is effective in approximately 80%
ABM from metalloproteinases or immature
of selected recurrent erosion patients.21,22
basement membrane proteins, thus
Treatment failure generally tends to occur
interrupting cellular adhesions of the
when the surgeon treats too small an area,
basement membrane.
and erosions then develop outside of the
treated area.
Anterior stromal puncture
In 1986, McLean et al described a significant
innovation in the surgical management
of resistant corneal erosions, which they
termed anterior stromal puncture.19 Initial
methods involved the use of a straight
20-gauge needle to make multiple shallow
penetrations through the epithelium
into anterior corneal stroma (see Figure
4). Following several reports of corneal
Excimer photo-therapeutic
keratectomy
Phototherapeutic keratectomy (PTK) using
excimer laser technology involves treating
Bowman’s layer, resulting in a modified,
roughened surface to anchor the corneal
epithelium.23 The patient’s epithelium is
usually removed mechanically by debriding
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06/06/14 CET
Surgical ‘options’
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with a spatula or blade, or using an alcohol
solution. Once the epithelium is removed, the
laser is used to treat Bowman’s layer.
As the excimer laser uses a flat treatment
profile for standard PTK, the treatment
usually results in a post-operative refractive
shift towards hyperopia. By combining PTK
with photo-refractive keratectomy (PRK),
the treatment creates an opportunity to
treat both RCES and refractive error in one
procedure. Combining PTK and PRK can
reduce or eliminate ametropia, improve the
best-corrected vision by reducing the surface
irregularity of the dystrophic epithelium, and
resolve the recurrent corneal erosions.
Despite questions regarding cost and
refractive shift, excimer PTK is an important
treatment for recurrent erosions, especially
in patients whose corneal erosions are
associated with marked basement membrane
dystrophy. In addition, patients with
corneal erosions caused by anterior corneal
dystrophies, such as superficial variant
of granular dystrophy and Reis-Bücklers’
dystrophy, may be excellent candidates for
excimer PTK.
Alternative ‘treatments’
Three case reports by a single
ophthalmologist who treated RCES patients
with botulinum toxin injections to the
orbicularis muscle have been reported.24 All
three patients had reduced RCE episodes but
required multiple injections on several followup appointments to stay symptom free. The
Conclusion
Figure 5 Retro-illuminated slit lamp
appearance immediately after anterior stromal
puncture. Note that the area of anterior
basement abnormality (box) extends beyond
the limits of the treated erosive epithelium.
Image reproduced from Rubinfeld RS et al27
author notes a study describing an ‘absent’
or ‘weak’ Bell’s phenomenon in patients with
RCEs as compared to controls, and a 78%
prevalence of abnormal Bell’s phenomenon in
patients without a predisposing condition for
their RCE in the same study.25 The proposed
mechanism of improvement in RCE symptoms
was a decreased effect of the orbicularis
muscle during REM sleep in patients with
an abnormal Bell’s phenomenon, limiting
nocturnal erosions.
Finally, an obscure treatment comes from
the German literature, describing hypnosis for
the treatment and prevention of RCES.26 The
author describes a case study where he uses
hypnosis and suggestions to treat a colleague
with corneal erosion. The patient remained
symptom free for 20 months.
Although recurrent corneal erosion
syndrome is a well-known disorder of the
corneal epithelium, research concerning
the aetiology and best treatment is
ongoing. Prevailing practice trends
seem to advocate medical treatment
with topical lubrication, cycloplegia and
antibiotic coverage or bandage contact
lens for first time corneal abrasions.
Long-term nocturnal lubrication is
encouraged for patients with recurrent
erosions. These patients are also treated
with all efforts to maximise a healthy tear
film, including oral doxycycline. When
medical therapy fails, relatively simple
surgical interventions may offer relief and
improve quality of life for the patient. The
decision as to which surgical correction is
preferable will likely depend on surgical
resources and surgeon experience.
RCES can have a huge impact on the
patient’s quality of life, so the threshold
for surgical intervention is low. The
recovery to being symptom free and
a more routine sleep pattern is much
faster with a relatively simple surgical
procedure. However, despite the best
medical and surgical efforts, RCES will
recur in a subset of patients, frustrating
both the doctor and the patient. When
both parties understand the relapsing
nature of this disease, the treatment
process may become more acceptable
to both.
Exam questions
References
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