Recurrent Corneal Erosion Syndrome (RCES), a corneal epithelial adhesion disorder, is a painful, often frightening, and sometimes incapacitating condition of the cornea. Corneal epithelial cells undergo erosions and results in denuded areas on the corneal surface. These areas then re-epithelise, the process recurs and the epithelial cells slough again. With many patients, erosions are characteristically episodic in nature.
Hansen in 1872, first described a set of symptoms consistent with RCES, and referred to the disorder as ‘intermittent neuralgic vesicular keratitis’. Von Szily in the year 1900, described principal features of RCES. Paul Chandler in 1945, divided the syndrome into a macroform and a microform type, with the macroform being associated more frequently with trauma. However, later observations confirmed that the two forms may occur simultaneously and there is no sharp distinction between them.
RCES may be diagnosed at almost any age and affects men and women equally. Even though the majority of patients give history of trauma, an underlying factor should be suspected when there is no history of trauma or surgery. Patients with RCES usually present with unilateral involvement, and the most commonly affected part is central part of the cornea just below the pupil. When the underlying cause is corneal dystrophy, symptoms are more often bilateral, localisation of the loosely adherent epithelium is more variable, and the management of symptoms often complicated. Trauma to the epithelium may be caused by a fingernail, plant material, sharp domestic objects, or the edge of a piece of paper. Salzmann’s nodular degeneration is another common acquired disorder that may be associated with recurrent corneal erosion syndrome. Rarely, cases may occur spontaneously without any obvious predisposing factor.
Most corneal erosions occur during the night or early morning hours and are described as an abrupt ripping sensation generally followed immediately by sharp pain, a marked foreign body sensation, watering, photophobia, visual disturbances, and often lid swelling. Some patients have mild symptoms every few months or years, and some experience severe, incapacitating, frequent erosions causing pain and other symptoms lasting for hours or days at a time.
In some patients with recurrent erosion, the epithelial defects never fully heal, and loose sheets of epithelium slide over the surface of the eye with each blink. These patients experience constant pain and may be some of the most distressed individuals. The unpredictable nature of recurrent erosions often heightens anxiety in patients. Patients may experience acute pain suddenly and would be unable to work or participate in normal activities for hours or days at a time.
Patients may be relatively free of symptoms, except for perhaps a mild ocular foreign body sensation or vague ‘awareness’ of the affected eye between episodes of erosions. This sensation of awareness can be most noticeable in dry, cold or windy environments.
It is not uncommon for patients with severe erosions to display signs of depression and anxiety. Since most of the erosions occur during sleep or on awakening, some patients fear falling asleep and experience varying degrees of insomnia. Disruption in normal sleep patterns may exacerbate psychological stress as well as the experience of the symptoms. Anxiety may even make erosions more frequent by causing patients to open their eyes more quickly on awakening and by inducing more rapid eye movements (REMs) as well as interfering with normal blinking and tear production.
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Nema HV, Nema Nitin. Textbook of Ophthalmology. Jaypee- Highlights Medical Publishers (P) Ltd. 2012. P 157.
Bowling Brad, Kanski'sClinical Ophthalmology- A Systematic Approach. Eighth Edition. Elsevier, 2016. P 211.
Das S, Seitz B. Recurrent corneal erosion syndrome [Review]. Surv Ophthalmol 53(1): 3, 2008.
Hansen E. Om den intermittirende keratitis vesiculosa neuralgica of traumatisk oprindelse. Hospitals-Tidende 1872; 15: 201- 203.
Von Szily. Ueber disjunction des Hornhautepithels. Arch F Ophthalmol 1900; 51: 486.
Chandler PA. Recurrent erosion of the cornea. Am J Ophthalmol 1945; 28: 355- 363.
Patients with RCES may experience ocular (eye) symptoms (may be triggered by a trivial mechanical trauma), typically on awakening, such as:
RCES may be associated with trauma or anterior corneal dystrophies.
In case of trauma, the initial insult causing corneal abrasion is commonly a slicing type injury, caused by a fingernail, brush, edge of a paper or even branch of a tree. The trauma to the eye is usually minor. Injuries induced by fingernails to the cornea are particularly at high risk of progressing to RCES. Old literature refers to RCES as ‘fingernail keratitis’. Injuries with fingernails, paper, or tree branches are more likely to induce RCES as compared to injuries with objects such as glass, rock or metal. Corneal trauma involving penetration into deeper stroma is less likely to induce RCES.
Causes of RCES are either primary or secondary depending on whether the basement membrane complex abnormalities are intrinsic or acquired. Secondary erosive disorders encompass all the conditions except corneal dystrophies. RCES is classified as (Das et al, 2008):
I Primary (Intrinsic):
- Cogan’s micro-cystic (map-dot-fingerprint) dystrophy (most common dystrophy causing RCES).
- Reis- Bϋcklers dystrophy.
- Thiel- Behnke dystrophy.
- Lattice dystrophy.
- Macular dystrophy.
II Secondary (Acquired):
- Band shaped keratopathy.
- Salzmann’s nodular degeneration.
- Traumatic epithelial abrasions.
- Chemical and thermal injury.
- Floppy eyelid syndrome.
- Meibomian gland dysfunction.
- Bacterial keratitis.
- Viral keratitis.
- Laser in situ keratomileusis (LASIK).
- Photorefractive keratectomy (RCES is rare).
- Diabetes mellitus.
- Epidermolysis bullosa (a mucocutaneous autoimmune disease).
The pathophysiology of RCES is only partially understood. Normal adhesion of the corneal epithelium depends primarily on structures known as attachment complexes, which are composed of elements from the basal epithelial cell, basement membrane, Bowman’s membrane and corneal stroma.
Electron microscopic examination and immunohistochemical staining methods shows that these elements possibly include hemidesmosomes, basal lamina, lamina densa, lamina lucida, anchoring fibrils, laminin, fibronectin, and Types IV and VII collagen. Abnormalities of epithelial adhesion resulting in recurrent erosions may be associated with previous traumatic abrasions or with corneal dystrophies.
Following injury, corneal epithelial defect is filled rapidly by epithelial cells sliding from adjacent epithelial basal layers. After this, epithelial cells begin mitosis and produce supra-basal epithelial cell layers. Sliding of basal epithelial cells can take place over either pre-existing basement membrane or bare stromal collagen. If the basement membrane remains intact after trauma, the new epithelial cell layer becomes firmly attached within a week. However, if the basement membrane is removed due to injury, some corneas appear unable to re-form normal attachment complexes, resulting in recurrent erosions occurring up to many years after the original injury.
Patients of RCES develop pain, watering, redness and photophobia that may vary from mild to severe. Some present with disease every day, but others have recurrences that may vary from every week or month to longer periods of time without any symptoms. Typically, pain is more severe at night or upon waking in the morning and may be related to REM during sleep or on opening of the eyelid. Patients are usually aware of this and they try to open the eyes gently every morning, but others refer that they are awakened in the middle of the night because of the pain. In acute phase of the disease, corneal erosion is always present, commonly in the lower half of the cornea, irrespective of the aetiology. This area of the cornea is in permanent contact with the tear film and lower lid and is most exposed to the evaporative dry eye disease.
The combination of a previous history of minor trauma to the involved eye, episodes of pain on awakening, and a rough irregular area of healing epithelium, is diagnostic of RCES.
Comparing patients following trauma with patients who had RCES secondary to epithelial basement membrane dystrophy, patients with epithelial basement membrane dystrophy were significantly more likely to be symptomatic.
Careful slit lamp examination is needed to find the subtle signs of this syndrome, since the epithelium in many cases had already healed. The appearance of the cornea on slit lamp examination between the episodes of clinical symptoms may be normal. Sometimes, however, various degrees of epithelial or sub-epithelial oedema, located in the area of former erosion, may be seen during the asymptomatic intervals. This oedema may be subtle (minimal bedewing), discernible only with retro-illumination on slit lamp. Alternatively, a fine linear sub-epithelial opacity of fine bubbles or a distinct sub-epithelial bulla may be visible.
Clinical signs at slit- lamp (bio-microscopy) may show:
In many cases, no signs are found, and then the patient is instructed to return immediately after the next episode of pain, without allowing time for the epithelium to heal and cover the erosion. This will facilitate proper diagnosis and correct location of the lesion for the purpose of treatment.
Features of acute attack or during the first few days following the attack, in corneal epithelium:
The midline below the horizontal meridian is usually the last area to re-epithelise, and the closure lines at this area are predisposed to frequent breakdown. In addition, this is the area of maximal exposure, since it opposes the line of lids closure.
When no obvious signs of RCE are evident on the slit lamp examination, the presence of impaired epithelial adhesion is detected by:
Test for epithelial adherence: Epithelial adherence may be tested with a dry cellulose sponge, which is gently rubbed over the area of suspected epithelial erosion. If the intact epithelial sheet is moveable by the sponge, then the lack of adequate epithelial-stromal adhesion is suspected. Loosely adherent epithelium folds or break down, when touched with the tip of the sponge under local anaesthesia. Explore the inferior and central cornea, but any part may be affected.
Corneal topography (using computerised videokeratography): Corneal topography often reveals focal areas of corneal flattening (called corneal topographic lagoons) in eyes with RCES. This finding is important in those patients having frank symptoms but do not show epithelial abnormalities. Corneal topography may show an irregular ocular surface, which may explain visual symptoms such as diminution of vision or monocular diplopia.
Histology: The ultra-structural changes associated with RCES include:
Confocal microscopy: Confocal microscopy in patients with RCES associated with anterior corneal dystrophies, discloses structural changes in the basal epithelium, basement membrane, Bowman’s membrane, anterior stroma, and corneal neurons.
Electron microscopy: Electron microscopy shows absence of hemidesmosomes and in some cases the absence of entire thickness of basement membrane. Thinning and splitting of basement membrane may also be present. Epithelial cells may be responsible for abnormal production and attachment of the basement membrane. The presence of high number of mitochondria with abnormal shape in the basal epithelial cells, seen as intracellular vacuoles, suggests an abnormal metabolic activity.
Recurrent breakdown of corneal epithelium may be seen in:
Management should be carried out under medical supervision.
Till date, no single therapy is found to be definitive and sufficiently effective. The therapy of RCES is palliative rather than curative. The disease may be annoying, but is not vision threatening.
Goals of management:
These goals are not easily achieved, and the chronic course of resistant cases of RCES may be frustrating for both patient and physician. Typically, a stepladder approach, beginning with conservative measures and moving on to invasive intervention, is followed. Adjuvant therapy e.g. cycloplegics, offer additional relief in symptoms.
Over the years, multiple treatment strategies were developed, including topical conservative treatments, such as hypertonic lubricants, soft bandage contact lenses and various aggressive surgical modalities, such as anterior stromal puncture and phototherapeutic refractive keratectomy, which aim at creating a new basement membrane-epithelial interface.
Tailoring the proper treatment strategy to each patient is the key to a successful control of RCES.
Medical therapy includes:
The majority of cases are mild and do well with these conservative treatments (topical lubricants and hyper-osmotic agents), which are effective in relieving pain and promoting initial epithelial growth. However, these modalities will not reduce the likelihood of recurrences.
Useful advice for patients is to move their eyes slowly to the left and right before opening them, and to gradually retract the lower lid, to facilitate gradual separation between the tarsal conjunctiva and the corneal epithelium. This slower separation of the cornea from the tarsal conjunctiva will prevent the shearing force created on the corneal epithelium during abrupt lid opening, and will prevent the erosion.
Other medical therapy includes:
These contact lenses should be used under close medical supervision, since long-term continuous use of contact lenses may lead to bacterial keratitis and neovascularisation. However, silicone hydro-gel extended wear contact lenses, in recent years, have significantly increased the safety of long-term use of bandage contact lenses.
Soft bandage contact lenses are often not effective in preventing further erosions except in cases where abnormalities in lid anatomy play a significant causative role in the erosions.
In patients where consistent, aggressive medical management fails to resolve the erosions, surgical therapy may be required.
Indications of surgery:
Choice of surgical approach is determined by:
Surgical therapy may be highly effective. Over the years, a series of surgical procedures have been described for RCES, including diamond burr polishing of Bowman’s membrane, anterior stromal puncture with an insulin needle or with neodymium- doped yttrium aluminium garnet (Nd:YAG) laser, and excimer laser phototherapeutic keratectomy (PTK). As these procedures result in high success rates and carry low risks, it is advisable not to defer the surgical options if the medical therapy fails. Historically, debridement and then superficial keratectomy were the first surgical approaches to the treatment of RCES, and these procedures are still in use today.
The suboptimal efficacy and limitations of this procedure derive from the fact that no significant modifications to enhance epithelial adhesions are made in Bowman’s membrane or other deeper corneal structures.
A technique known as alcohol delamination of the corneal epithelium has been proposed to improve the efficacy of debridement in the treatment of recurrent erosions. Debridement and removal of abnormal or reduplicated epithelium are most effective in cases where localised areas of such epithelium interfere with visual acuity by inducing refractive changes.
The optimum candidate for this procedure is one having:
- Spontaneous multiple erosions in different areas of cornea.
- No history of trauma.
- Severe basement dystrophy, resulting in poor vision.
- Large areas of loosely adherent irregular epithelium.
Once re-epithelialisation has occurred, hyper-osmotic ointments are used to lubricate and protect the delicate healed epithelial tissue.
Failure of anterior stromal puncture treatment in few patients is due to small treatment area, and erosions then develop outside of the treated area. A second, larger treatment can often resolve erosions in patients in whom the initial procedure is unsuccessful.
Anterior stromal puncture has also been tried/ used in patients with corneal erosions associated with bullous keratopathy. Although corneal stromal oedema is generally well tolerated, rupture of epithelial bullae and the resulting corneal erosions in these patients can be very painful. For some of these bullous keratopathy patients with erosions, who are poor candidates for penetrating keratoplasty because of poor visual potential or medical contraindications, anterior stromal puncture has been shown to be a useful treatment. Anterior stromal puncture can also be used to control painful erosions in patients with bullous keratopathy who are awaiting corneal transplantation. The optimum patients for this type of treatment are those whose bullae are localised and not diffusely distributed throughout the cornea.
The aim is to remove a 6.0-mm diameter of thick anterior stromal layer. The eye is patched after putting cycloplegic and antibiotic drops. Bandage contact lens may be required during the postoperative period.
PTK results in a higher rate of success for RCES following trauma than corneal dystrophies.
Advantages of PTK are:
- Removal of corneal tissue with extreme precision.
- Precision helps in preventing damage to the non-ablated area.
- Simultaneous treatment of wider areas.
Disadvantages of PTK are:
- Postoperative discomfort.
- Hypermetropic (hyperopic) shift is caused by the central flattening of the cornea. More advanced PTK, based on flying spot beam profiles, is associated with fewer undesirable refractive changes, compared to those with older, broader beam lasers.
Advantages of diamond burr polishing are:
- The results of diamond burr polishing are comparable to those of PTK.
- A subtle granular sub-epithelial deposit is initially noticed which clears in about three months postoperatively. A study on RCES and anterior basement membrane dystrophy showed significantly less haze after diamond burr polishing as compared to PTK.
- Diamond burr polishing is a simple, less expensive procedure with fewer recurrences as compared to PTK.
- Diamond burr polishing can be used to treat RCES involving the visual axis.
Complications may be:
Preventive measures/ deterrence for RCES may be: