Synonyms: RCES, RES

The cornea is made up of three layers: the internal, single-layer cell of endothelium, the central stroma which makes up the bulk of the cornea and the multi-layered external epithelium. Recurrent corneal erosion syndrome (RCES) refers to the situation where there is disturbance of the epithelial basement membrane, resulting in defective adhesion of the epithelium to Bowman's membrane, causing recurring cycles of epithelial breakdown. Multiple recurrences are common, because the basal epithelial cells require at least 8 to 12 weeks to regenerate or repair the epithelial basement membrane.

Aetiology

• The most common cause that triggers the process off is superficial trauma to the cornea (including micro-trauma caused by contact lens wear).¹ A clean cut abrasion (such as a paper cut) is more likely to cause the problem than a ragged abrasion. Other types of trauma may include alkali burns, foreign bodies and exposure keratopathy. Typically, recurrent corneal erosion syndrome (RCES) develops 3-10 days after the insult but in some cases, it may not develop until several months later.
• It may arise spontaneously but in the presence of risk factors relating to the cornea such as corneal dystrophies (notably, epithelial basement membrane dystrophy but a large number of others too), dry eye syndrome and exposure keratopathy.
• There may be more unusual trigger factors (all involving disruption of the epithelial basement membrane) such as following cataract surgery or refractive surgery. Other iatrogenic causes include vitrectomy (surgical removal of the vitreous) and photocoagulation.²
• Systemic diseases which may predispose to this condition include:
  • Diabetes¹
  • Junctional epidermolysis bullosa
  • Alport's syndrome
  • Münchhausen's syndrome
  • Malnutrition
• Drugs associated with the development of RCES include:
  • Thiomersal (found in contact lens solutions).
  • High-dose topical neomycin.
  • Topical paromomycin.
  • Topical diamidines and propamidine.
  To a certain extent, all topical anaesthetic medication causes some degree of epithelial cell damage but this is most marked with cocaine, which is associated with RCES more than others.
• A variety of RCES associated with autosomal dominant inheritance has been described but is rare.

Epidemiology²

• There are no accurate statistics relating to the exact incidence and prevalence of this condition as it often goes undiagnosed or misdiagnosed.
• It tends to occur slightly more commonly in females.
• It is a problem seen in adulthood, usually from the fourth decade of life onwards, unless it is associated with one of the corneal dystrophies (e.g. Reis-Bücklers dystrophy) or Alport's syndrome, in which case it can arise in children.

Presentation³

History

In its early stages, the condition may be asymptomatic. Later, there may be recurrent attacks of acute pain (typically towards the end of sleep or on waking) associated with lacrimation, photophobia and a foreign body sensation. There may be an associated blepharospasm (inability to open the lids) and blurring of the vision. Some patients report glare and halos around lights (this occurs if corneal oedema develops). The problem may be unilateral or bilateral. Symptoms may gradually subside over the course of the day and then start all over again the next morning. The unpredictability of these episodes may lead to an associated anxiety.

Assessment

• Check the patient's visual acuity (a drop of local anaesthetic will temporarily relieve the pain and the associated blepharospasm).
• Examine as much of the anterior segment of both eyes (even if symptoms are unilateral) as your instruments allow you to. This includes fluorescein staining of the cornea. The idea is to rule out other possible differentials (see list below).
• If you think this is recurrent corneal erosion syndrome (RCES), refer: the urgency depends on the degree of pain the patient is in. Same day referral is required for an acute attack.
• In the ophthalmology clinic, the anterior segment of the eye will be assessed with an emphasis on the state of the epithelium (macroerosions, microerosions or a roughening of the corneal surface). There may be associated oedema or disruption at deeper levels of the cornea. The degree and location of the disruption will affect the visual acuity. The fellow eye will also be examined for evidence of corneal dystrophy or other predisposing factors. There may be no signs to see at all in mild cases as the epithelium can heal within a few hours: the diagnosis can be made on history alone if this is typical. Severe cases can result in marked corneal changes which are quantifiable by corneal topography (a 3-dimensional mapping of the corneal surfaces giving gradients at each point, so producing an ordnance survey map of the cornea).

Differential diagnosis²

• Corneal abrasion.
• Corneal foreign body.
• Contact lens-related problem.
• Dry eye syndrome.
• One of a variety of corneal dystrophies.
• Floppy eyelid syndrome.
• Herpes simplex keratitis.
• Other form of keratitis.

Recurrent corneal erosion syndrome (RCES) can also occur following prolonged eye patching.

Investigations

Diagnosis is made on history and examination. Severe cases may warrant corneal topography (see 'Assessment', above) to outline the degree of corneal damage or help in the diagnosis of a corneal dystrophy (most of which are diagnosed on examination).

Staging

There is no formal staging of recurrent corneal erosion syndrome (RCES) but a note is made of the depth of corneal involvement, as this dictates treatment options and prognosis.

Management

There is insufficient evidence to inform definitive management guidelines.⁴

Primary care

• The best time for a patient to be seen is first thing in the morning: in mild cases, signs will have resolved within a few hours.
• A patient suspected of suffering from recurrent corneal erosion syndrome (RCES) should be referred to the local ophthalmology unit. The degree of urgency depends on the severity of pain.
• Should a non-urgent referral be made and there is an interval between referral and ophthalmology consultation, do not be tempted to manage these patients with topical anaesthetic agents, as these disrupt epithelial healing and aggravate the problem. Topical lubricants and oral analgesia are a reasonable initial plan.
• Avoid a pressure patch: this is best applied (if at all) in the eye clinic once the problem has been assessed.
• The patient may be discharged once the condition seems to have stabilised. However in some patients, this can be a recurring problem and, should the treatment regime given not contain the symptoms any longer, re-referral is entirely appropriate.

Topical treatment

First-line management involves increasing the lubrication of the surface of the eye and optimising the tear film.³ The patient should be advised about lid hygiene and use of warm compresses. The patient is started on topical antibiotic ointments (usually erythromycin or bacitracin) and prescribed artificial tears. Hypertonic solutions and ointments (NaCl ointment and drops) can be used if the corneal epithelium is oedematous.
• A bandage contact lens (a clear, non-refracting soft lens) can be used to allow the corneal surface to heal properly. In some patients, this may have to stay on for several months. Patients need advice on the dangers of infection with long-term use.
• If these measures are unsuccessful, oral doxycycline (100 mg bd) and steroid drops are used.

Surgery

There are several procedures used:

• Anterior stromal puncture may be performed. This is a minor procedure carried out under local anaesthetic in the eye clinic. Numerous tiny punctures are made away from the central visual axis, which induces cicatrisation and promotes more permanent epithelial adherence. It may be performed using Nd-YAG laser.⁵
• Alcohol delamination is a newer procedure that has shown good efficacy and safety.⁶
• Keratectomy is the removal of corneal tissue and is reserved for severe and difficult cases (usually in patients with associated corneal dystrophies).³ It involves either laser treatment or surgical removal (knife, diamond burr): the entire epithelium is removed and allowed to regrow from new over the following 5-7 days. It can be carried out more than once if the problem recurs. It can also be combined with a refractive correction.

Complications

• Infectious keratitis.
• Corneal scarring.
• Decreased visual acuity (due to either of the above).

Prognosis

With the right treatment, generally the prognosis is good with most patients responding well to topical treatment.² This relies on any underlying conditions being diagnosed and treated and good patient education on the long-term management. Few patients will have their vision permanently affected.

Prevention

Prophylaxis revolves around long-term lubrication in the first instance, e.g. night-time lubricating ointment for three months.⁷ The success of this approach depends on the patient understanding the importance of continuing this treatment in the absence of symptoms. More severe cases may require a protective bandage contact lens. There is evidence to suggest that a 12-week course of systemic tetracyclines (e.g. oxytetracycline 250 mg bd) may be beneficial (they inhibit matrix metalloproteinase activity and promote epithelial stability).³ Other preventative measures include:²

• Avoiding dry/irritating environments (e.g. cigarette smoke).
• Wearing protective glasses, especially where exposure might risk abrasion (e.g. gardening, painting).
• Keeping well hydrated.
• Avoid rubbing the eyes
• Applying long-lasting lubricating ointments last thing at night.
• Avoiding sleeping in late.
• Learning to wake with eyes closed and still (and having lubricant within reach by the bedside).

Document references

1. Ramamurthi S, Rahman MQ, Dutton GN, et al; Pathogenesis, clinical features and management of recurrent corneal erosions. Eye (Lond). 2006 Jun;20(6):635-44. Epub 2005 Jul 15. [abstract]
2. Verma A et al, Corneal Erosion, Recurrent, Medscape, Jun 2009
3. Ewald M, Hammersmith KM; Review of diagnosis and management of recurrent erosion syndrome. Curr Opin Ophthalmol. 2009 Jul;20(4):287-91. [abstract]
4. Watson SL, Barker NH; Interventions for recurrent corneal erosions. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD001861. DOI: 10.1002/14651858.CD001861.pub2.
5. Tsai TY, Tsai TH, Hu FR, et al; Recurrent corneal erosions treated with anterior stromal puncture by neodymium: Ophthalmology. 2009 Jul;116(7):1296-300. Epub 2009 May 8. [abstract]
6. Singh RP, Raj D, Pherwani A, et al; Alcohol delamination of the corneal epithelium for recalcitrant recurrent corneal Br J Ophthalmol. 2007 Jul;91(7):908-11. Epub 2007 Feb 14. [abstract]
7. Das S, Seitz B; Recurrent corneal erosion syndrome. Surv Ophthalmol. 2008 Jan-Feb;53(1):3-15. [abstract]

Internet and further reading

• Recurrent corneal abrasions/erosion, Kinshuck D, Good Hope Eye Department, Heart of England NHS Foundation Trust; (excellent patient resource with good diagrams)
• Kanski J. Clinical Ophthalmology: A Systematic Approach (5th Ed) Butterworth Heinemann (2003)