Article

RESEARCH REVIEW

MANAGEMENT OF RECURRENT CORNEAL EROSIONS

Recurrent corneal erosion (RCE) is a commonly encountered clinical condition that involves abnormalities of both the corneal epithelium and the basement membrane. RCE can cause mild, moderate, or severe ocular pain, photophobia, lacrimation, and eventual scarring of the cornea that could result in vision loss. The recurrence of episodes of corneal erosion makes this condition chronic in nature and quite frustrating to both eyecare professionals attempting to manage RCE and to patients suffering from RCE. The single most frequent contributor to RCE was initial corneal trauma (45%); the presence of epithelial basement membrane dystrophy (EBMD) contributed to 29% of cases; and a combination of both contributed to 17% of cases (Reidy et al, 2000). Symptoms of RCE typically are reported upon awakening from sleep, most likely because of defects created in the adhesion complexes that hold the epithelial cells to the basement membrane along with abnormalities of the basement membrane itself. Upon opening of the eyelid, a shearing force results in epithelial avulsion (Ramamurthi et al, 2006). The most accepted management methods incorporate a stepped approach. The box below shows a treatment algorithm.

Treatment Algorithm for Recurrent Corneal Erosions

Initial Acute Treatment of Corneal Erosions

  1. Acute pain management
       a. Topical anesthetic at presentation
       b. Topical NSAIDs at presentation and, if needed, for short-term use (few days max)
       c. Oral analgesics if necessary
  2. Infection control—topical broad-spectrum antibiotic
  3. Promotion of healing of epithelial defect
       a. Bandage contact lens, short-term use (along with prophylactic antibiotic drop)
       b. Bandage contact lens, long-term use (three to six months of extended wear along with prophylactic antibiotic drop)
  4. Lubrication and promotion of epithelial adherence (use from weeks to months)
       a. Hypertonic eye drops (NaCl) during the daytime q.i.d.
       b. High-oncotic-pressure eye drops during the daytime t.i.d.
       c. Hypertonic ointment at bedtime

Medical Treatment of Recalcitrant and Recurrent Corneal Erosions

  1. Inhibition of inflammation and MMPs
       a. Oral doxycycline (25mg to 50mg b.i.d. p.o. for a minimum of eight weeks)
       b. Topical “soft” steroid drops (q.i.d. for two weeks and then b.i.d. for six weeks)
  2. Autologous serum eye drops (6x/day for three months, then 4x/day for three months)
  3. Amniotic membrane application (following debridement along with topical antibiotic drop)

Interventional and Surgical Treatment of Recalcitrant and Recurrent Corneal Erosions

  1. Epithelial debridement
  2. Alcohol corneal delamination
  3. Anterior stromal puncture
       a. 25-gauge turned needle
       b. Pulsed Nd:YAG
  4. Phototherapeutic keratectomy
  5. Diamond burr polishing of Bowman’s membrane

Corneal wound healing is mediated by a group of enzymes known as matrix metalloproteinases (MMPs), which are sourced from corneal epithelial cells and fibroblasts. Specifically, MMP-2 and MMP-9 have been found in higher than normal levels in the tear fluids of patients who have RCE. Elevated levels of these MMPs are thought to dissolve old and newly forming basement membrane and also may degrade the adhesion complexes (Garrana et al, 1999), resulting in RCE.

MGD in RCE

A study by Hope-Ross et al (1994) reported a higher incidence of meibomian gland dysfunction (MGD) in patients who had non-traumatic RCE. Acne rosacea was also seen in higher numbers of these MGD cases. Staph colonization of lid margins of MGD and rosacea patients results in elevated levels of bacterial lipases. These lipases act on meibomian secretions to produce toxic free fatty acids that interfere with the healing process and break down the intercellular hemidesmosomes and adhesion complexes, which would predispose patients to RCE (Dougherty and McCulley, 1986). Additionally, elevated levels of interleukin-1 and MMP-9 have been found in patients who have rosacea-related MGD, pointing to inflammation as a key factor (Afonso et al, 1999).

The goal of all forms of treatment for RCE is quick healing of the erosion along with reformation of healthy adhesion complexes between the epithelium and the basement membrane. All of this should take place without the development of infection.

Immediate Therapy for RCE

Patients presenting with RCE symptoms will have significantly variable degrees of discomfort. For cases involving more severe discomfort or pain, immediate attention to pain management is important. When pain is dramatic, a topical anesthetic is often required to even get a good look at the eye. However, topical anesthetics should not be used for prolonged periods of time due to the risk of delayed wound healing and ophthalmic anesthetic toxicity (persistent epithelial defects, stromal edema, infiltrates, endothelial damage, corneal ulceration, thinning, and perforation) (McGee and Fraunfelder, 2007).

So, to address the pain for a relatively longer time period, the use of topical nonsteroidal anti-inflammatory agents (NSAIDs) can be highly effective. A study by Thiel and co-workers (2017) reviewed the literature that evaluated the use of NSAIDs as compared to topical anesthetics and topical cycloplegic agents for pain management in cases of corneal abrasions. The authors stated that trials involving the use of NSAIDs for pain management in corneal abrasion have shown a statistically significant decrease in subjective pain experienced by patients. They failed to find evidence to support the efficacy of cycloplegia for pain management in these cases. They also failed to find support for the use of topical anesthetics beyond immediate pain management. However, clinically, practitioners frequently use topical anesthetics for immediate pain relief in the office along with the use of topical NSAIDs used both in-office and for limited time periods (days) ongoing. Note that the use of topical NSAID drops for RCE is an off-label use. The use of topical cycloplegia is still used often even though evidence for its use in pain management is questionable (Thiel et al, 2017). Use of oral analgesics is rarely needed in cases of RCE.

Once ocular pain/discomfort have been alleviated, address the acute episode. The goal of this phase of therapy is to promote re-epithelialization and to re-establish a functional basement membrane/epithelial complex. The healed epithelium needs to remain intact so that the adhesion complexes can reform (Ramamurthi et al, 2006). Typical approaches to prevent infection include the use of broad-spectrum topical antibiotic drops along with hypertonic eye drops and hypertonic ophthalmic ointment at bedtime. Hypertonic agents produce an osmotic gradient that draws fluid from the epithelial layer and promotes adherence of basal epithelial cells to the underlying Bowman’s membrane (Mandić et al, 2007).

Bandage contact lenses (BCLs) are used by some for both the acute and long-term management of RCE. BCLs assist in pain management, promote healing of the epithelial defect, and may reduce the likelihood of future recurrences. Fraunfelder and Cabezas (2011) conducted a small-scale study and found that 75% of subjects treated with extended wear BCLs for three months had no recurrence of RCE after approximately one year of follow up.

Management of Recurrence and Recalcitrant Cases

With long-term management of RCE, address MGD, blepharitis, and rosacea, if present. Topical and oral treatment reduces the recurrence rates of RCE (Hope-Ross et al, 1994). Inhibition of MMPs (Ramamurthi et al, 2006; Zdravko et al, 2007) will reduce the likelihood of RCE, and agents that do so are believed to be effective. Both oral tetracyclines (such as doxycycline) and topical steroids reduce levels of MMPs and can be used successfully in recalcitrant cases of RCE (Dursun et al, 2001).

The use of autologous serum (AS) eye drops has also been suggested for the long-term management of RCE. Multiple elements found in AS—specifically fibronectin—promote epithelial migration and anchorage (Fujikawa et al, 1981). A study by Ziakas et al (2010) found that, with the use of AS over six months, 85% of subjects did not have recurrence over a 2.5-year period.

Similarly, the use of amniotic membrane (AM) application has also been effective in reducing subsequent episodes of RCE. Typically, epithelial debridement of loose/unstable tissue is required prior to the application of the AM. A study by Huang et al (2013) found that, after epithelial debridement and application of a cryopreserved AM, there was less than a 10% recurrence rate in the follow-up period of 13.7 months ± 2.2 months.

Interventional and Surgical Management

The intent of epithelial debridement is to remove loosely adherent epithelium; however, debridement alone has not been effective for successful reduction in recurrence. Anterior stromal puncture (ASP) was initially proposed by McClean et al (1986) based on formation of reactive scarring to enhance epithelial adhesion. The use of a 25-gauge turned-end needle has resulted in reports of up to 80% success (McLean et al, 1986; Malecha, 2004). ASP can also be successfully performed with a pulsed neodymium-doped yttrium aluminum garnet (Nd:YAG) laser (Geggel, 1990; Rubenfeld et al, 1991). Recently, anterior segment optical coherence tomography has been used to guide application of ASP with success (Oikonomakis et al, 2018).

Phototherapeutic keratectomy (PTK) removes epithelium and partial areas of the basement membrane with great precision. This procedure has been highly effective in RCE therapy by promoting reformation of the adhesion complexes. Success rates range between 60% and 100% (Dausch et al, 1993; Fagerholm et al, 1993). Remember to consider the subsequent hyperopic refractive influence of the procedure. This effect has been minimized with contemporary laser profiles (Maini and Loughnan, 2002).

Diamond burr polishing of Bowman’s membrane also improves outcomes in RCE over simple debridement. In fact, outcomes may be comparable to PTK at a much lower cost and with a lower likelihood for haze development (Soong et al, 2002; Sridhar et al, 2002; Mamikonyan et al, 2018).

Finally, alcohol delamination of the cornea is effective in the management of recalcitrant cases of RCE. Results again are similar to those of PTK, with the advantage of significantly lower cost (Singh et al, 2007; Ní Mhéalóid et al, 2018).

Concluding Remarks

A stepped approach to RCE allows eyecare professionals to successfully manage this commonly encountered condition. The evidence-based literature supports the efficacy of such an approach. CLS

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