Recurrent Erosions of the Cornea Epidemiology and Treatment

James J. Reidy, M.D., M. Peter Paulus, M.D., and Suma Gona, M.D.

Purpose. To evaluate the epidemiologic characteristics of a large dler’s macroform erosions) may last for several days and are often clinical population of patients with recurrent erosions of the cor- associated with more severe pain, eyelid edema, decreased visual nea. The efficacy of different modalities of treatment was also acuity, and extreme photophobia.4 Slit-lamp examination reveals evaluated. Methods. A retrospective chart review of all patients either a frank epithelial defect or a large area of edematous non- with the diagnosis of recurrent corneal erosion treated between adherent epithelium. The majority of patients has a history of January 1990 and December 1998 was performed. Results. Clini- preexisting superficial trauma to the cornea or evidence of epithe- cally confirmed recurrent erosions were identified in 104 patients. 4–6 There were 36 males and 68 females. A history of trauma was lial basement membrane dystrophy (EBMD). Poor adhesion of present in 47 patients (45%), 30 patients (29%) had epithelial the epithelium is thought to be owing to underlying abnormalities basement membrane dystrophy (EBMD), and 18 patients (17%) in the epithelial basement membrane and its associated filament had both a history of trauma and evidence of EBMD. More than network.7–9 The precise nature of these abnormalities has yet to be 87% of all erosions occurred on the inferior third of the cornea. fully elucidated. Conservative therapy was used as the primary treatment in 52 Recurrent erosions often respond to conservative treatment with patients with a recurrence rate of 6%. Corneal stromal micropunc- topical lubrication, cycloplegia, patching, or placement of a thera- ture was performed on 38 patients with a recurrence rate of 40%. peutic contact lens.4,6,8,10 Despite conservative therapy, a large Eleven patients had epithelial debridement with a recurrence rate percentage of patients will continue to have minor and major re- of 18%. Four patients had a superficial keratectomy with a dia- currences.11 This subgroup of patients may benefit from surgical mond bur with a recurrence rate of 25%. Only one patient had an therapy. Epithelial basement membrane debridement,6 corneal excimer phototherapeutic keratectomy, and she had a minor recur- 12,13 rence posttreatment. Conclusions. In our series, the distribution of stromal puncture, and superficial keratectomy with a diamond 14 15 trauma and EBMD in patients with recurrent erosions of the cornea bur or with the excimer laser have been shown to be helpful. is roughly equivalent. Conservative therapy was effective in ap- A large study comparing all these different surgical modalities has proximately one half of the patients. All surgical treatment mo- not yet been reported. This paper is a retrospective analysis of a dalities were associated with recurrences. Those patients with both large number of patients with recurrent corneal erosions that were EBMD and trauma were more likely to have a recurrence after treated with both conservative measures and all the various surgi- treatment. More effective treatment modalities for recurrent ero- cal modalities. The epidemiologic features of this patient popula- sions of the cornea need to be investigated. tion are also reviewed. Key Words: Recurrent erosions—Cornea—Epithelial basement membrane dystrophy—Trauma—Anterior corneal stromal micropuncture—Keratectomy—Excimer laser. MATERIALS AND METHODS

The charts of all patients seen in a referral-based university cornea practice by a single practitioner (J.J.R.) between January Recurrent erosions of the cornea have been recognized as a 1990 and December 1998 with a confirmed diagnosis of recurrent distinct clinical entity for well over a century.1–3 Episodes are erosion of the cornea were identified by means of a customized characterized by the sudden onset of eye pain, usually at night or computer database program. A total of 104 patients was identified. upon first awakening, accompanied by redness, photophobia, and On initial presentation, a detailed history combined with a com- tearing. Individual episodes may vary in severity and duration. plete ophthalmologic examination was reviewed, and salient in- Minor episodes (Chandler’s microform erosions) usually last from formation extracted and transposed onto a data sheet. Gender, age, 30 minutes to several hours and typically have an intact epithelial laterality, history of trauma, frequency, location and type of recur- surface at the time of examination.4 More severe episodes (Chan- rence, presence of EBMD, prior treatment, treatment of acute epi- sode, need for retreatment, and type of retreatment were all re- corded. A diagnosis of recurrent erosion was made based on the presence of a spontaneously occurring focal epithelial defect or an area of loosely adherent, edematous epithelium combined with a history of trauma or the presence of EBMD. A characteristic history of multiple minor and/or major recurrence usually occurring upon awaking was noted in all cases. EBMD was diagnosed by means of slit-lamp biomicroscopy using a combination of tech-

767 768 J.J. REIDY ET AL.

eye. With the patient was seated at a slit-lamp biomicroscope, a bent 25-gauge needle (Fig. 1A and B specifically designed for stromal puncture (Surgical Specialties Corp., Reading, PA, U.S.A.) was attached to a 3-mL syringe and multiple superficial punctures were placed approximately 0.5 mm apart in the affected area. Treatment extended at least 1 mm into normal epithelium bordering the lesion (Fig. 2A and B. Topical fluorescein was sometimes instilled immediately before treatment to help better define the affected area to be treated. Immediately after treatment a disposable contact lens was placed, and the patient instructed to use topical polymyxin B + trimethoprim drops twice daily, and topical 0.5% ketorolac four times daily as needed to control discomfort. After 1 week, the contact lens was removed and the drops discontinued. The patient was then placed on hypertonic saline ointment at bedtime for a period of at least 3–6 months.

Epithelial Basement Membrane Debridement Patients with preexisting EBMD in whom topical lubricant treatment failed and who presented during an acute erosion (11 patients) were treated with epithelial basement membrane debridement. After topical 0.5 tetracaine and topical polymycin B + trimethoprim drops were instilled, the patients were sterilely prepped and draped, and an eyelid speculum placed into the eye. With the assistance of an operating microscope, all loosely adherent epithelium was removed with a combination of sterile surgical sponges niques that included broad-beam illumination, retroillumination, back illumination, and fluorescein staining. All patients were examined and treated by the same examiner (J.J.R.).

Management Management of the acute episodes varied depending on the severity of the recurrence, presence of an epithelial defect, size of the defect, presence of EBMD, and the type of previous management. Nonsurgical management (52 patients) included patients who had received no prior treatment who presented between acute erosive episodes. These patients were placed on 5% hypertonic saline ointment at bedtime and topical tear replacement drops during the day. Patients who presented with an acute erosion who had received no prior treatment were fit with a disposable therapeutic contact lens and placed on topical polymyxin B + trimethoprim drops twice daily, topical 0.5% ketorolac four times daily as needed to control discomfort, and one drop 1% cyclopentolate. The contact lens was left in place on a continual basis for a period of 2 weeks and then exchanged with a new lens that was left in place for an additional 2 weeks. After 4 weeks, the lens was removed and the patient placed on hypertonic saline ointment for a period of at least 3–6 months.

Corneal Stromal Micropuncture In cases in which conservative management had failed and no EBMD was present (38 patients), corneal stromal puncture was performed. Only those patients in whom the pupillary axis was not involved were treated with this modality. The treating physician chose to avoid treatment within the visual axis because there was limited information concerning the long-term outcome of such treatment.13 Immediately before treatment, topical 0.5 tetracaine and topical polymycin B + trimethoprim drops were instilled into the affected

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and a Kimura spatula. Bowman’s layer was then lightly debrided with a number 15 Baird-Parker scalpel blade to remove the epithelial basement membrane. Immediately after treatment, a dispos- control discomfort. For systemic control of pain, acetaminophen able contact lens was placed, and the patient instructed to use with codeine was also dispensed. The therapeutic contact lens was topical polymyxin B + trimethoprim drops twice daily, and topical left in place for a period of 2 weeks, and then the patient asked to 0.5% ketorolac four times daily as needed to control discomfort. use hypertonic saline ointment at bedtime for a period of at least For systemic control of pain, acetaminophen with codeine was also 3–6 months. dispensed. The therapeutic contact lens was left in place for a period of 2 weeks. After removal of the contact lens, the patients Phototherapeutic Keratectomy were instructed to use hypertonic saline ointment at bedtime for a One patient who had recurrences despite several treatments with period of 3–6 months. corneal stromal puncture had an excimer laser phototherapeutic keratectomy (PTK). After topical 0.5 tetracaine and topical poly- Superficial Keratectomy with a Diamond Bur mycin B + trimethoprim drops were instilled, the patients were Four patients had a major recurrence after either epithelial base- sterilely prepped and draped, and an eyelid speculum placed into ment membrane debridement or after two treatments with corneal the eye. With the assistance of an operating microscope, all loosely stromal micropuncture. In these patients, a superficial keratectomy adherent epithelium was removed with a combination of sterile with a diamond bur was performed. After topical 0.5 tetracaine and surgical sponges and a Kimura spatula. The cornea was treated topical polymycin B + trimethoprim drops were instilled, the pa- with 20 pulses (5 ␮m) using an excimer laser (Apex laser; Summit tients were sterilely prepped and draped, and an eyelid speculum Technology, Waltham, MA, U.S.A.). A 6.5-mm diameter was placed into the eye. With the assistance of an operating micro- used. Immediately after treatment, a disposable contact lens was scope, all loosely adherent epithelium was removed with a com- placed, and the patient instructed to use topical polymyxin B + bination of sterile surgical sponges and a Kimura spatula. Bow- trimethoprim drops twice daily, and topical 0.5% ketorolac four man’s layer was then lightly buffed with a diamond bur (Fig. 3 times daily as needed to control discomfort for the first 24 hours. attached to a low-speed electrically driven hand-piece (Storz For systemic control of pain, acetaminophen with codeine was also model E 0819; Storz, St. Louis, MO, U.S.A.). Immediately after dispensed. The therapeutic contact lens was left in place until the treatment, a disposable contact lens was placed, and the patient epithelium had healed, and then the patient was asked to use hy- instructed to use topical polymyxin B + trimethoprim drops twice pertonic saline ointment at bedtime for a period of at least 3–6 daily, and topical 0.5% ketorolac four times daily as needed to months.

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RESULTS induced erosions. Our data demonstrated that those patients having A total of 104 patients with a confirmed diagnosis of recurrent both preexisting EBMD and superficial trauma were more likely to erosions of the cornea was identified. Of the 104 patients, 36 were have persistent symptoms after treatment. male (35%), and 68 were female (65%). The mean age of the The recurrence rate after anterior cornea stromal puncture in our patients was 43 years (range, 14–77). The presence of predisposing study was ∼40%. Most of these patients (74%) had a history of factors is noted in Table 1. The locations of the erosions were corneal trauma. Recurrence was defined as the chronic persistence categorized into eight distinct zones (Fig. 4. Most erosions (87.5%) of any symptoms of recurrent erosion after treatment. Other au- occurred in the lower third of the cornea. Patients were treated with thors who reported higher success rates with anterior cornea stro- conservative measures, epithelial debridement, stromal micro- mal puncture considered patients having minor erosive symptoms puncture, superficial keratectomy, or excimer PTK (Table 2. The that did not interfere with daily activities as successes.12,13 overall recurrence rate was 30/104 (29%). Table 3 breaks down The recurrence rate after epithelial basement membrane de- recurrence rates after specific treatment modalities. Tables 4–7 bridement was ∼18%. The majority of these patients (82%) had examine the incidence of different predisposing factors as they evidence of EBMD. An insufficient number of diamond bur kera- relate to individual treatment modalities. tectomies and excimer laser PTKs was performed on this group of patients to make a valid comparison of efficacy with the other surgical treatment modalities. O¨ hman et al.15 reported on 76 pa- DISCUSSION tients with recurrent corneal erosions treated with excimer laser PTK and found that >50% had persistent symptoms. Half of these Previous studies of patients with recurrent erosions of the cornea 6,10 required further treatment. Reports detailing the long-term results have evaluated the results of conservative management. No of diamond bur keratectomy have yet to be published. studies published to date compare the long-term success rates of all Corneal epithelium that heals over the area of initial abrasion the current nonsurgical and surgical treatment modalities. This often adheres poorly to the underlying corneal stroma. Khou- study consists of patients with recurrent corneal erosions referred dadoust et al.16 reported that firm adhesion between the stroma and to a single cornea specialist, many of whom had already failed epithelium occurred within 1 week in experimentally wounded conventional management with topical lubrication and patching. rabbits when the underlying basement membrane was intact. How- There was a greater number of women in this study compared to 6,10 ever, when the basement membrane was removed at the time of other studies that had a roughly equal gender distribution. The wounding, they found that firm epithelial adhesion took as long as average age of our patients was similar to that noted in previous 8 weeks to form. Aitken et al.(9) examined samples of loosely reports,6,10 as was the location of the erosions over the inferior one 10 adherent corneal epithelium from 25 patients with traumatic cor- third of the cornea. Roughly two thirds of our patients had a neal erosions. They found epithelial separation occurred either history of trauma, fingernail injuries being the most common below the level of the anchoring plaques or at the level of the ∼ cause. Evidence of EBMD was present in 50% of the patients. epithelial cell membrane. The anchoring fibrils are thought to be Half of the patients responded to treatment with either topical responsible for the firm adhesion of the epithelial basement mem- hypertonic saline ointment or a therapeutic contact lens. Only three brane to the underlying corneal stroma.8,17 Thus, superficial injury patients in this group had persistent symptoms. However, the re- to the cornea that abrades the corneal epithelium, the basement maining 50% of the patients failed conservative management and 10 membrane, and the anchoring fibril network could result in de- required surgical intervention. Hykin et al. reported on a series of layed epithelial adherence to the underlying stroma. 117 patients with recurrent erosions. These authors initially re- The aim of current surgical treatment is to induce a healing ported that >95% of their patients were successfully managed with 10 response in the corneal stroma that somehow results in firmer conservative therapy, with 70% of patients being symptom free. epithelial adherence. This is based on the observation that patients However, when the same authors contacted these patients 4 years with superficial injury or infection involving the anterior corneal later, they found that ∼60% of those contacted continued to have 11 stroma that results in scarring rarely experience corneal erosions. persistent symptoms of recurrent erosion. These authors also Fibroblast proliferation in the anterior stroma that has been ob- noted that patients with EBMD were more likely to experience served to occur in experimental corneal wounding, as well as after persistent symptoms compared to those patients who had trauma-

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REFERENCES

1. Hansen E. Intermittirende keratitis vesiculosa neuralgica af traumatisic Oprindelse. Hospitalstid 1872;201. 2. Szily A von. Ueber Disjunction des Hornhautepithels. Arch fur Ophth 1900;31:486. 3. Vogt A. Lehrbuch und Atlas der Spaltlampenmikroskopie de Lebenden Auges. Berlin: Springer, 1930:244–6. 4. Chandler PA. Recurrent erosion of the cornea. Am J Ophthalmol 1945; excimer laser photorefractive keratectomy, may stimulate the for- 28:353–63. 5. Waring GO, Rodrigues MM, Laibson PR. Corneal dystrophies. I. Dys- mation of new anchoring fibrils in the stroma resulting in firmer trophies of the epithelium, Bowman’s layer and stroma. Surv Ophthal- epithelial adhesion.18 mol 1978;23:74–82. Garrana et al.19 observed that gelatinase activity (MMP-2 and 9) 6. Brown N, Bron A. Recurrent erosion of the cornea. Br J Ophthalmol was up-regulated in epithelial specimens in patients with recurrent 1976;60:84–96. 7. Dohlman CH. The function of the corneal epithelium in health and cornea erosions. Gelatinases alter the epithelial basement mem- disease. Invest Ophthalmol Vis Sci 1971;10:383–407. brane during wound healing by cleaving collagen types IV, V, VII, 8. Kenyon KR. Recurrent corneal erosion: pathogenesis and therapy. Int and X.20 They also act on the adhesive macromolecules fibronectin Ophthalmol Clin 1979;19:169–95. and laminin that are thought to mediate attachment of the basal 9. Aitken DA, Zeidoon AB, Lee WR. Ultrastructural study of the corneal epithelial cells to the basement membrane.21 Activation of MMPs epithelium in the recurrent erosion syndrome. Br J Ophthalmol 1995; 79:282–9. on a chronic basis may either be a result of, or the cause of, poor 10. Hykin PG, Foss AE, Pavesio C, et al. The natural history and man- epithelial adherence that leads to the symptoms of recurrent cor- agement of recurrent corneal erosion: a prospective randomized trial. neal erosion. Eye 1994;8:35–40. Most patients with the macroform of recurrent erosions of the 11. Heyworth P, Morlet N, Rayner S, et al. Natural history of recurrent erosion syndrome—a 4 year review of 117 patients. Br J Ophthalmol cornea can be converted to the microform by means of conven- 1998;82:26–8. tional or surgical treatment. Although this allows patients to re- 12. McLean EN, MacRae SM, Rich LF. Recurrent erosion: treatment by sume their daily activities, they often continue to experience some anterior stromal puncture. Ophthalmology 1986;93:784–8. degree periodic eye pain. Currently available surgical modalities 13. Rubinfeld RS, Laibson PR, Cohen EJ, et al. Anterior stromal puncture cannot reliably guarantee elimination of minor erosive symptoms. for recurrent erosion: further experience and new instrumentation. Ophthalmic Surg 1990;21:318–26. New treatment modalities, such as topical protease inhibitors, need 14. Buxton JN, Fox ML. Superficial epithelial keratectomy in the treat- to be investigated to find more reliable means of providing symp- ment of epithelial basement membrane dystrophy: a preliminary re- tomatic relief. Further elucidation of the underlying pathophysiol- port. Arch Ophthalmol 1983;101:392–5. ¨ ogy of this disorder is also needed. 15. Ohman L, Fagerholm P, Tengroth B. Treatment of recurrent corneal erosions with the excimer laser. Acta Ophthalmol 1994;72:461–3. This was a retrospective study, and therefore conclusions re- 16. Khoudadoust AA, Silverstein AM, Kenyon KR, et al. Adhesion of garding the comparative efficacy of the different treatment mo- regenerating corneal epithelium: the role of the basement membrane. dalities must be interpreted with caution. A large-scale, prospec- Am J Ophthalmol 1968;65:339–48. tive, randomized study would help to determine the optimal treat- 17. Gipson IK, Spurr-Michaud SJ, Tisdale AS. Anchoring fibrils form a ment strategy for this frequent problem. complex network in human and rabbit cornea. Invest Ophthalmol Vis Sci 1987;28:221–0. 18. Wu WCS, Stark WJ, Green WR. Corneal wound healing after 193-nm excimer laser keratectomy. Arch Ophthalmol 1991;109:1426–32. 19. Garrana RMR, Zieske JD, Kaminski AE, et al. The expression of matrix metalloproteinases (MMP) in human recurrent erosion epithe- lia. Invest Ophthalmol Vis Sci 1998;39:S89. 20. Ye HQ, Azar DT. Expression of gelatinases A and B, and TIMPs 1 and 2 during corneal wound healing. Invest Ophthalmol Vis Sci 1998;39: 913–21. 21. Berman M. The pathogenesis of corneal epithelial defects. Acta Oph- thalmol 1989;67(suppl 192):55–64.

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Recurrent Erosions of the CorneaNANARECURRENT CORNEAL EROSIONSJ.J. REIDY ET AL.767–77119CQ99-21962000 Epidemiology and Treatment James J. Reidy, m.d., M. Peter Paulus, m.d., and Suma Gona, m.d. Purpose. To evaluate the epidemiologic characteristics of a large clinical population of patients with recurrent erosions of the cornea. The efficacy of different modalities of treatment was also evaluated. Methods. A retrospective chart review of all patients with the diagnosis of recurrent corneal erosion treated between January 1990 and December 1998 was performed. Results. Clinically confirmed recurrent erosions were identified in 104 patients. There were 36 males and 68 females. A history of trauma was present in 47 patients (45%), 30 patients (29%) had epithelial basement membrane dystrophy (EBMD), and 18 patients (17%) had both a history of trauma and evidence of EBMD. More than 87% of all erosions occurred on the inferior third of the cornea. Conservative therapy was used as the primary treatment in 52 patients with a recurrence rate of 6%. Corneal stromal micropuncture was performed on 38 patients with a recurrence rate of 40%. Eleven patients had epithelial debridement with a recurrence rate of 18%. Four patients had a superficial keratectomy with a diamond bur with a recurrence rate of 25%. Only one patient had an excimer phototherapeutic keratectomy, and she had a minor recurrence posttreatment. Conclusions. In our series, the distribution of trauma and EBMD in patients with recurrent erosions of the cornea is roughly equivalent. Conservative therapy was effective in approximately one half of the patients. All surgical treatment modalities were associated with recurrences. Those patients with both EBMD and trauma were more likely to have a recurrence after treatment. More effective treatment modalities for recurrent erosions of the cornea need to be investigated. Key Words: Recurrent erosions—Cornea—Epithelial basement membrane dystrophy—Trauma—Anterior corneal stromal micropuncture—Keratectomy—Excimer laser. Recurrent erosions of the cornea have been recognized as a distinct clinical entity for well over a century.1–3 Episodes are characterized by the sudden onset of eye pain, usually at night or upon first awakening, accompanied by redness, photophobia, and tearing. Individual episodes may vary in severity and duration. Minor episodes (Chandler’s microform erosions) usually last from 30 minutes to several hours and typically have an intact epithelial surface at the time of examination.4 More severe episodes (Chandler’s macroform erosions) may last for several days and are often associated with more severe pain, eyelid edema, decreased visual acuity, and extreme photophobia.4 Slit-lamp examination reveals either a frank epithelial defect or a large area of edematous nonadherent epithelium The majority of patients has a history of