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Optometric Study Center: June 2007
 
Put a Stop to Recurrent Corneal Erosion
This painful, persistent problem can strike without warning and be difficult to get rid of. Fortunately, several treatment modalities can resolve this recalcitrant condition.
By Robert A. Ryan, O.D.

Self-Assessment Examination Print Version
 

Release Date: June 2007

Expiration Date: June 30, 2008
Goal Statement: Recurrent corneal erosion is a severely painful condition that can persist for months or years. Fortunately, several treatment modalities—from conservative therapy to surgical options— can resolve this recalcitrant condition. This course discusses how RCE occurs and provides a stepwise approach to treating it.

Faculty/Editorial Board: Robert A. Ryan, O.D.

Credit Statement: This course is COPE qualified for 2 hours of CE credit. COPE ID 19805-AS. Please check with your state licensing board to see if this approval counts towards your CE requirement for relicensure.
Joint-Sponsorship Statement: This continuing education course is joint-sponsored by the Pennsylvania College of Optometry.
Disclosure Statement: Dr. Ryan has no relationships to disclose.

Mornings are painful enough. Imagine how surprised and distraught you’d feel if you woke up with a severely painful eye accompanied by lacrimation, photophobia and blurred vision.

Your eye was fine the night before, but as the fog of sleep lifts, you realize that you’ve had these symptoms before. Why— and how— did they come back? And, how can you get rid of this problem for good?

This is recurrent corneal erosion (RCE) syndrome, one of many ocular surface diseases that can be chronic in nature, often persisting for months to years. Fortunately, several treatment modalities can resolve this recalcitrant condition. This article discusses how RCE occurs and how to treat it.

Precipitating Factors

Recurrent corneal erosion syndrome is defined as the presence of an epithelial defect that spontaneously recurs without obvious cause. However, the condition often can be traced to some earlier trauma, specifically a shearing-type abrasion of the anterior corneal surface from a sharp edge of stationery, a tree branch or a fingernail. Other possible origins include:

  • Corneal surgery. The area adjacent to an incisional keratotomy or the margin of a lamellar flap may experience a disruption of the basement membrane and become iatrogenically susceptible to infection.
  • Anterior corneal dystrophy. Patients with conditions such as epithelial basement membrane dystrophy (EBMD), lattice dystrophy, Reis-Bückler’s dystrophy and granular dystrophy have a greater risk of developing RCE.
  • Diabetes mellitus. Recognized systemically as a basement membrane disease, diabetes predisposes afflicted individuals to RCE as well.
Evidence of lattice dystrophy associated with RCE.

The pathophysiology of RCE suggests that the defect may penetrate the full thickness of the epithelium, including the basal lamina and perhaps into Bowman’s layer. The basement membrane then becomes fragmented, folded, split and reduplicated, causing the epithelial cells to attach to loose layers of basement membrane.

Tiny epithelial inclusion cysts are then created by “confused” subgroups of basal cells that adhere to free basement membrane. These generate new basement membrane, which curls inward and attaches to itself. (Obviously, the combination of ragged-instrument trauma and an anterior corneal dystrophy is particularly troublesome.)

While re-epithelialization typically occurs rapidly and completely to protect the cornea from microbial assault, the basement membrane is incapable of such accelerated repair. Without competent hemidesmosomes and anchoring fibrils, the recovered epithelium remains vulnerable to repeated erosion. These episodes commonly occur upon awakening, as the combination of subtle epithelial edema, the shearing force of the eyelid, and a thin pre-ocular tear film is too great for the compromised adherence to withstand.

An eye with corneal stromal dystropy associated with RCE. Notice the gray, granular leisions.

A small degree of corneal edema is typical in about 4% of the normal population.1 This can be explained largely by two physiological events. First, the active transport pump mechanism of the endothelium slows during sleep, reducing its impact on maintaining corneal deturgescence.

Second, eye closure during sleep retards evaporation of the pre-ocular tear film; this can exacerbate the problem. This effectively decreases tear film osmolarity, diminishing the osmotic effect on the semi-permeable epithelium.

Corneal abrasions are typically caused by the presence of a foreiegn body in the eye. RCE can result if the abrasion does not properly heal.

Other factors in RCE include the presence of corneal gutatta, Fuchs’ endothelial dystrophy, and more superficial keratopathy related to keratitis sicca, corneal exposure or medicamentosus.

A history of contact lens use may further alter the corneal deturgescence process. Lens movement, surface quality, pervaporation and permeability all can affect corneal integrity. Lens care systems and their interactions with various contact lens polymers have been implicated in corneal insult.2 Then again, safe and compliant lens wear actually may enhance the ability of the cornea to resist edema associated with the closed eye state.3

All these influences on corneal physiology explain the varied and intermittent clinical course of RCE.

An eye with Reis-Buckler’s dystrophy associated with RCE before undergoing phototherapeutic keratectomy.
 
The same eye following phototherapeutic keratectomy. Note the less cloudy appearence of the sclera.

The Conservative Approach

A prudent approach to managing RCE is to explore and exhaust conservative treatment as the initial course of action. This includes:

  • Thorough patient education. Most important, be sure the patient continues and complies with therapy for at least eight to 12 weeks, as further insult to the recovering attachments prolongs the treatment process.5
  • Copious lubrication therapy (every one to two hours while awake). Systane LiquiGel (Alcon) is a good choice because of its propensity to bind to hydrophobic corneal regions and adjust viscosity to the pH of the particular ocular environment. Other lubricating agents may prove equally efficacious. This dosing frequency calls for preservative-free, single-use ampules to promote epithelial recovery.
  • Use of a hyperosmotic ointment, such as Muro 128 5% (sodium chloride, Bausch & Lomb), at bedtime. If you suspect the patient has nocturnal lagophthalmos, recommend forced closure with eye pads or hypoallergenic tape applied to the lids. The hyperosmotic agent helps offset the increase in stromal hydration caused by epithelial compromise.
  • Punctal occlusion, when appropriate, to maximize therapeutic efficacy. Occlusion of the lacrimal passage can normalize the ocular surface and pre-ocular tear film, and maximize the efficacy of therapeutic adjuncts.

    One precaution: The traumatized epithelium may recruit cytokines and other inflammatory mediators, and occlusion may interfere with their normal egress through the canalicular system. This, in turn, leads to an inflammatory assault on the ocular surface.6 In short, punctal occlusion is likely to be beneficial in the absence of significant ocular surface inflammation.

  • Cycloplegia to manage ocular discomfort. While repeated use of topical anesthetics delays healing, many patients seek relief from the chronic discomfort associated with RCE. The use of a cycloplegic, such as homatropine 5% b.i.d., may reduce sensitivity in some patients. If more extensive treatment is necessary, an oral nonsteroidal anti-inflammatory drug (NSAID), such as Toradol (ketorolac tromethamine, Roche Pharmaceuticals) 10mg q.i.d. limited to five days maximum, is indicated to calm the discomfort.
Punctal occlusion
Punctal occlusion can assist in tear retention, which may prevent recurrence of RCE.



Corneal Pain and Repair

For most patients, pain is the deciding factor that leads them to seek immediate medical care. While each of us has experienced pain to some degree, the sensation of pain is still poorly understood.

Recent evidence suggests a possible reason for the apparent disparity among individuals in sensing pain. Neuroscientists at the University of Michigan have identified a gene that leads to the production of catechol-O-methyltransferase, or COMT, the enzyme responsible for metabolizing signal messenger dopamine in the brain.4 The process triggers increased production of natural painkillers known as endorphins, which limits a person’s sense of pain.

This is of particular importance in the eye, as the corneal epithelium contains more terminal nerve endings than any other tissue in the body. The corneal nerve endings do not reach the most superficial squamous cells; instead, they terminate in the wing cell layer. This may explain the frequent lack of pain in very superficial corneal insults.

When evaluating the recovery of the disrupted epithelium, it helps to understand the mechanism of corneal repair. In response to trauma, the corneal epithelium increases the synthesis of an extracellular matrix, facilitating a chemotactic response. Epithelial growth factor (EGF) and transforming growth factor-beta (TGF-ß) direct transient amplifying cells, which arise from limbal stem cells, to proliferate at the wound margin. Stratification may increase to a 20- to 50-cell layer thickness as mitosis accelerates, promoting migration across the depths of the defect in an effort to bridge the erosion.

This process rapidly restores the barrier function of the corneal epithelium, providing protection from edema and microbial infection. Often, this process sufficiently allows the episode to resolve on its own. Patients may simply tolerate the discomfort, refrain from seeking professional advice and self-medicate with topical non-prescription agents. While some episodes may prove to be self-limiting, others clearly require attention due to their severity or chronicity.

 

Anterior basement membrane dystropy
Anterior basement membrane dystrophy can often be a predisposing factor for RCE.

 

Bandage Lenses

Therapeutic bandage contact lenses have been used to enhance the effectiveness of more conservative therapy by controlling hydration, restoring comfort and establishing a protective barrier to the shearing forces of the eyelid. To achieve these benefits, the patient must follow a continuous-wear schedule (with silicone hydrogel contact lenses) for 10 to 12 weeks without interruption.7

My typical approach is to use a PureVision (balafilcon A, Bausch & Lomb) or a Focus Night & Day (lotrafilcon A, CIBA Vision) lens on a continuous-wear basis, taking into account any refractive needs. I have the patient return for re-evaluation and in-office lens replacement every three to four weeks for a minimum of three cycles.

The proper fit should demonstrate subtle movement to meet metabolic demands but should not be so constrictive that it mechanically disrupts cellular repair. Careful inspection must reveal a hydrated lens that is freely mobile prior to the exchange.

If the ocular surface is irregular without a true epithelial defect, avoid prophylactic antimicrobials with bandage lens therapy. If frank defects are present, prescribe a fluoroquinolone-soaked bandage lens, and instruct the patient to apply one drop three times daily until the defect closes. Monitor these individuals more regularly than the aforementioned three- to four-week interval, perhaps every three to four days until resolution.

Don’t forget to consider the potential effect of antibiotics and any preservatives on the rate of corneal healing. Topical antibiotics by their very nature are toxic to the corneal surface and therefore interfere with recovery. Preservative agents compound this counterproductive effect and provide good reason to limit exposure to these substances. Use non-preserved medications when possible.

An example of a therapuetic bandage lens. Bandage leses help to control hyrdation and provide extra protection from the eyelashes.

Take note that the management outlined above is not universally accepted. One study found that use of an NSAID combined with a bandage lens allowed for much quicker recovery than use of a bandage lens or NSAID alone.8 Another study, however, determined that bandage lens therapy was less effective than topical medications and yielded a higher complication rate.9

When treating patients, consider the medicolegal ramifications of off-label usage. Careful monitoring and full patient disclosure are essential.

Combination Therapy

Other novel approaches have expanded our management choices for patients who suffer from RCE. For many years, we have recognized the antimicrobial benefits of oral tetracyclines (tetracycline, doxycycline and minocycline) in the treatment of ophthalmic chlamydial infections. Cases of chronic posterior lid disease and meibomian gland dysfunction respond well to this class of antibiotics due to its positive effect on fatty acids and meibomian gland sebum.

Oral tetracyclines, along with steroid therapy, appear to inhibit matrix metalloproteinase (MMP), a factor in inflammation.10 MMP facilitates extracellular matrix deposition and degradation, and elevated levels of MMP hinder corneal repair.

To investigate this, researchers at the Ocular Surface and Tear Center of the Bascom Palmer Eye Institute in Miami reported on a series of seven patients with RCE that proved recalcitrant to conventional therapy.10 Treatment was aimed at counteracting MMP and consisted of 50mg oral doxycycline b.i.d. for two months along with a topical steroid t.i.d. in the affected eye for two to three weeks. All patients experienced pain relief, and the epithelial defects resolved within 10 days. There was no recurrence for the duration of the study.

The Amoils epithelial scrubber is used to remove epithelium prior to phototherapeutic keratectomy.

 

Phototherapeutic keratectomy is a fairly agressive surgical treatment for RCE. The procedure was performed on this eye a day earlier.

 

Surgical Treatment

When more conventional efforts fail, consider surgical options. Identify the area of involvement by careful examination, and document with photos, as available. This analysis will determine the most appropriate treatment to maximize the prognosis for complete remediation.

Surgical treatment options for RCE include:

  • Superficial keratectomy. Epithelial debridement of the involved area using a patent spatula aims to remove basement membrane irregularities, necrotic cells and cellular debris. The goal is to provide a smooth surface that encourages adherence of the basal epithelium. This is accomplished quite effectively with the aid of a biomicroscope. However, if your licensure does not permit this procedure, it is wise to refer the patient to a qualified corneal specialist.

    Anesthetize the cornea with several drops of proparacaine or tetracaine, and induce cycloplegia with atropine 1.0% for postoperative pain management. Position the patient comfortably and securely with the fellow eye gaze fixated. Use a lid speculum to secure the eyelids away from the treatment field. Remove epithelium in a centripetal direction to limit treatment to the compromised area, and remove any loose or redundant tissue.

    Alternatively, some practitioners advocate phototherapeutic keratectomy (PTK) 5µm to 10µm deep in the involved area to ensure a smooth stromal bed and potentially incite a more aggressive healing response.11 (Again, access to these excimer lasers and licensure constraints may require you to refer the patient.)

    Another alternative: One study reported on the use of the Amoils epithelial scrubber (AES) (Excimer Solutions, Inc.) to perform a superficial keratectomy in 26 eyes of 23 patients.12 The AES is an electric brush designed for removal of the epithelium prior to photorefractive keratectomy (PRK). At a mean follow-up of more than 21 months, as many as 88% of patients were symptom free.

    Whichever variation of keratectomy you choose, you must first irrigate the ocular surface thoroughly before performing the procedure. Next, apply a bandage contact lens soaked in a fourth-generation fluoroquinolone, namely Vigamox (moxifloxicin 0.5%, Alcon) or Zymar (gatifloxacin 0.3%, Allergan). (Note that Vigamox is preservative-free).

    Discharge the patient with instruc
    tions to continue antibiotic use three times daily in the treated eye. Follow up with the patient in 24 to 48 hours as the defect resolves to determine the next course of action.
Anterior stromal micropuncture uses a bent 25-gauge needle to place several closely spaced micropunctures into Bowman’s membrane.
  • Anterior stromal micropuncture. This method employs a bent 25-gauge needle to place several closely spaced micropunctures into Bowman’s membrane.13 Reserve stromal micropuncture for cases that do not involve the visual axis, as this procedure typically results in subepithelial fibrosis that may lessen vision.

    Micropunctures create foci of firm collagenous attachment that reach from the basement membrane into the sub-Bowman’s stroma within the region of poor epithelial attachment. Think of it as spot welding the epithelium to the anterior stroma. However, if the basement membrane is diseased, this technique does nothing to remove it.

    Prepare the patient for this procedure as described above. One difference, however: Micropuncture does not require debridement of the epithelial layer, but it should extend slightly beyond the apparent area of involvement. The treatment must penetrate 45µm to 50µm into the epithelium and 15µm to 20µm through Bowman’s layer into the anterior stroma.

    Use of an Nd:YAG laser in place of the 25-gauge needle has demonstrated favorable results.14 The goal of these treatments is to incite a sufficient healing response that encourages a solid relationship between the basal epithelium, basal lamina and Bowman’s membrane and extends into the anterior stroma.

A Stepwise Approach to RCE Management

Conservative therapy

  • Patient education
  • Copious lubrication therapy
      Increase frequency
      Liquid gel
      Preservative free
  • Hyperosmotic agents
      Ointments
  • Bandage contact lens therapy
      Silicone hydrogel
  • Mechanical closure of eyelids q.h.s.
      Tape lids
      Eye pad
      Moisture (swim) goggles
  • Punctal occlusion
  • Cycloplegia for pain management

Surgical management

  • Superficial keratectomy
      Epithelial debridement
      PTK/PRK
  • Stromal micropuncture
  • Alcohol delamination
  • Alcohol delamination. Researchers in the United Kingdom recently investigated the safety and efficacy of alcohol delamination of the corneal epithelium for recalcitrant RCE.15 They studied 20 eyes of patients with RCE who remained symptomatic despite topical lubrication and three months of using an extended-wear bandage contact lens. They treated patients with alcohol delamination and followed up at one week, one month and 12 months.

    Symptoms resolved in 15 eyes after one month of treatment. Three eyes had significant reduction of symptoms that were manageable with topical lubricants, and two eyes were lost to follow-up. There were no failures or intraoperative complications. The researchers concluded that alcohol delamination of the corneal epithelium is a safe and effective method for treating patients with recalcitrant RCE.

    There is some question as to whether RCE syndrome is a focal condition or a more diffuse, compromised adherence from limbus to limbus, extending well beyond the area apparent from biomicroscopic examination. There may be logic in performing nearly total epithelial debridement followed by excimer ablation, particularly in cases where subsequent satellite areas of erosion were documented. This underscores the importance of careful documentation early in the management process.

 

A recurrent corneal erosion can be a painful, troublesome condition that can create a substantial hardship for affected patients. Resolution of this chronic problem is extremely gratifying for both the patient and the doctor, and allows patients to return to a normal lifestyle. ■

Dr. Ryan is in group practice in Rochester, N.Y. He frequently lectures and publishes on anterior segment topics, and actively participates as an FDA clinical investigator for many contact lens manufacturers.

References

1. Fonn D, du Toit R, Simpson T, Vega J, Situ P, Chalmers R. Sympathetic swelling response of the control eye to soft lenses in the other eye. Invest Ophthalmol Vis Sci 1999;40 (13):3116-21.
2. Garofalo RJ, Dassanayake N, Carey C, et al. Corneal staining and subjective symptoms with multipurpose solutions as a function of time. Eye Contact Lens 2005 Jul;31(4):166-74.
3. Holden BA. The Glenn A. Fry award lecture 1988: The ocular response to contact lens wear. Optom Vis Sci 1989;66: 717-33.
4. Zubieta JK, Heitzeg MM, Smith YR, et al. COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science 2003 Feb 21;299(5610):1240-3.
5. Langston RHS, Machamer CJ, Norman CW, et al. Soft lens therapy for recurrent erosion syndrome. Ann Ophthalmol 1978;10:875-8.
6. Yen MT, Pflugfelder SC, Feuer WJ. The effect of punctal occlusion on tear production, tear clearance, and ocular surface sensation in normal subjects. Am J Ophthalmol 2001 Mar;131(3):314-23.
7. Holden BA, Mertz GW. Critical oxygen levels to avoid corneal edema for daily and extended wear contact lenses. Invest Ophthalmol Vis Sci 1984 Oct;25(10):1161-7.
8. Donnenfeld ED, Selkin BA, Perry HD, et al. Controlled evaluation of a bandage contact lens and a topical nonsteroidal anti-inflammatory drug in treating traumatic corneal abrasions. Ophthalmology 1995; 102(6): 979-84.
9. Williams R, Buckley RJ. Pathogenesis and treatment of recurrent erosion. Br J Ophthalmol 1985; 69:435-7.
10. Dursun D, Kim MC, Solomon A, Pflugfelder SC. Treatment of recalcitrant recurrent corneal erosions with inhibitors of matrix metalloproteinase-9, doxycycline and corticosteroids.
11. Baryla J, Pan YI, Hodge WG. Long-term efficacy of phototherapeutic keratectomy on recurrent corneal erosion syndrome. Cornea 2006 Dec;25(10):1150-2.
12. Hodkin MJ, Jackson MN. Amoils epithelial scrubber to treat recurrent corneal erosions. J Cataract & Refract Surg 2004 Sep; 30(9):1896-1901.
13. McLean EN, MacRae SM, Rich LF. Recurrent erosion. Treatment by anterior stromal puncture. Ophthalmology 1986 Jun;93(6):784-8.
14. Geggel HS, Maza CE. Anterior stromal puncture with the Nd:YAG laser. Invest Ophthalmol Vis Sci 1990 Aug;31(8):1555-9.
15. Singh RP, Raj D, Pherwani A, et al. Alcohol delamination of the corneal epithelium for recalcitrant recurrent corneal erosion syndrome. Br J Ophthalmol 2007 Feb 14; [Epub ahead of print].


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