Advancing wavelike epitheliopathy was first described by D'Aversa et al1 In their study, 11 eyes of 7 patients were seen with well-demarcated, centripetally advancing waves of irregular epithelium and subepithelial haze, originating from the upper aspect of the limbus. Identified risk factors included the use of topical antiglaucoma medications or contact lens care solutions, contact lens wear, past ocular surgery, acne rosacea, and atopic dermatitis. The condition was reported to respond to 1% silver nitrate applied to the superior aspect of the limbus. To our knowledge, no other cases have been documented. We describe a patient with advancing wavelike epitheliopathy and the confocal microscopic findings.
A 49-year-old white woman was referred for evaluation of corneal abnormalities. Her chief complaint was ocular discomfort and photophobia in both eyes for 1 month, and she had a history of daily soft contact lens wear in both eyes for 1 year. Her medical history was unremarkable. Best-corrected visual acuity was 20/20 OU. Slitlamp examination showed the presence of coarse irregular epithelium plaques originating from the superior aspect of the limbus in both eyes into the superior aspect of the cornea (Figure 1). At the subepithelial level, a diffuse haze was noted. The remainder of the ophthalmic examination, including examination of the conjunctiva, showed no abnormalities. The patient was examined using a prototype, white-light, tandem scanning, confocal microscope (LSU Eye Center, New Orleans, La) using a ×24/0.60 contact objective (Tandem Scanning Corp, Reston, Va). Ophthalmic examination was performed with liquefied hydroxypropyl methylcellulose as a coupling gel. Confocal microscopy showed the presence of atypical, elongated, and centripetally oriented cells with easily recognizable nuclei at the level of the abnormal epithelium in both eyes (Figure 2, left). At the subepithelial level, confluent hyperreflective images were detected (Figure 2, right). The areas adjacent to the plaques of irregular epithelium showed no abnormalities. The patient was treated with 1% silver nitrate applied to the superior aspect of the limbus. Subsequently, the symptoms subsided rapidly and complete resolution was noted clinically 1 month after the treatment. Few abnormal epithelial cells could still be demonstrated at the limbus in both eyes by confocal microscopy; however, the patient remained asymptomatic during the following 6 months and further treatment was not necessary.
In the superior cornea, plaques of coarse irregular epithelium revealed by fluorescein staining were seen in the both eyes. They were more notable in the left eye and seemed to originate from the upper aspect of the limbus. A faint subepithelial haze was also present.
Left, In both eyes, confocal microscopy revealed the presence of atypical elongated cells with centripetally oriented, long-axis, and hyperreflective nuclei. Right, At the subepithelial level, confluent hyperreflective images were found (original magnification ×210).
The clinical presentation of our patient is similar to that described by D'Aversa et al1 and could be easily differentiated from superior limbic keratoconjunctivitis and corneal pannus. Rapid response to 1% silver nitrate made the possibility of corneal epithelial dysplasia or carcinoma very unlikely.
D'Aversa et al postulated that abnormal limbal cells proliferate and migrate to the cornea. They disclosed parakeratotic alterations and underlying mononuclear cell infiltration in the limbal conjunctiva; however, they did not demonstrate cytological alterations in the corneal epithelium. Using the confocal microscope, we could identify the presence of highly atypical cells at the level of the epithelium. The subepithelial hyperreflective layer probably corresponds to the hazy structure seen on slitlamp examination and is compatible with fibrous tissue. Further studies are necessary to investigate its exact composition.
Our case supports the existence of the clinical entity described by D'Aversa et al1 and endorses that their treatment with silver nitrate may be clinically effective. Confocal microscopic findings of remaining abnormal epithelial cells after the treatment may account for the need of repeated treatments in some patients, as described by D'Aversa et al. Confocal microscopy enables noninvasive in vivo examination of the cornea and may allow diagnosis of advancing wavelike epitheliopathy by demonstrating the atypical elongated cells.
This study was supported in part by Public Health Service grants EY00346 (Dr S. Kaufman) and EY02580 and EY02377 (Dr H Kaufman), from the National Eye Institute, National Institutes of Health, Bethesda, Md; Department of the Army, Cooperative Agreement DAMD17-93-V-3013 (this does not necessarily reflect the position or the policy of the government, and no official endorsement should be inferred) (Drs Beuerman and H. Kaufman); an unrestricted departmental grant from Research to Prevent Blindness Inc, New York, NY (Dr Chiou); and grants from the Société Académique Vaudoise (Dr Chiou); the Swiss National Research Foundation (Dr Chiou); and the Verrey Foundation (Dr Chiou) Lausanne, Switzerland.
The authors do not have any commercial or proprietary interest in the products or companies cited in this article and do not have any financial interest or receive payment as a consultant, reviewer, or evaluator.
Reprints: Roger Beuerman, PhD, LSU Eye Center, 2020 Gravier St, Suite B, New Orleans, LA 70112-2234 (e-mail: firstname.lastname@example.org).
Chiou AG, Kaufman SC, Beuerman RW, Ohta T, Kaufman HE. A Confocal Microscopic Study of Advancing Wavelike Epitheliopathy. Arch Ophthalmol. 1999;117(1):123-124. doi: