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Advancing wavelike epitheliopathy is an uncommon, chronic or recurrent corneal disorder that may produce progressive visual disturbance and pose diagnostic challenges. The condition is characterized by well-demarcated, wavelike plaques of thickened corneal epithelium that typically extend from the limbus toward the visual axis. The etiology is incompletely understood, though associations with prior ocular surface injury, chronic epithelial stress, or subclinical inflammation have been reported. Risk factors include advanced age, chronic contact lens wear, and previous ocular surgery. The pathophysiology involves localized epithelial hyperplasia with abnormal adhesion to the underlying Bowman layer, potentially disrupting corneal transparency and optical quality. Clinically, patients present with visual blurring, glare, or subtle discomfort. Slit-lamp examination reveals characteristic wavelike epithelial changes. Diagnosis relies on careful clinical evaluation, supplemented by high-resolution anterior segment imaging or confocal microscopy when necessary. Management includes ocular surface optimization, removal of contributory mechanical or toxic factors, and targeted epithelial debridement for visually significant lesions. Complications may include recurrent epithelial defects or corneal scarring, but the prognosis is favorable with early recognition and appropriate intervention. This activity for healthcare professionals is designed to enhance learners’ competence in evaluating and managing advancing wavelike epitheliopathy. Participants will deepen their understanding of the condition’s epidemiology, proposed etiologic factors, pathophysiology, clinical presentation, diagnostic modalities, and best management practices. Improved skills will equip clinicians to collaborate with interprofessional teams to optimize care, minimize morbidity, and reduce recurrence in affected individuals. Objectives: Identify the clinical and diagnostic features suggestive of advancing wavelike epitheliopathy. Implement best practices for managing advancing wavelike epitheliopathy and addressing potential complications. Improve patient awareness of signs of advancing wavelike epitheliopathy, as well as treatment options and the need for regular ophthalmic follow-up, to minimize morbidity and recurrence.

Identify the clinical and diagnostic features suggestive of advancing wavelike epitheliopathy. Implement best practices for managing advancing wavelike epitheliopathy and addressing potential complications. Improve patient awareness of signs of advancing wavelike epitheliopathy, as well as treatment options and the need for regular ophthalmic follow-up, to minimize morbidity and recurrence. Collaborate with the interprofessional team to educate, treat, and monitor patients with advancing wavelike epitheliopathy to improve visual and functional outcomes. Access free multiple choice questions on this topic.

Advancing wavelike epitheliopathy (AWE) is a chronic or recurrent corneal disorder characterized by well-demarcated, wavelike plaques of coarse, thickened epithelium. Epithelial changes most commonly originate at the superior limbus and extend toward the visual axis, although some cases arise from the inferior limbus.[1] Corneal epithelial scrapings reveal no dysplasia or architectural irregularity, and the conjunctiva remains typically unaffected. Lesions may present unilaterally or bilaterally.[2]

The exact etiology of AWE remains unclear. The condition is believed to arise from chronic irritation or insult to the corneal epithelium. Reported triggers include prior ocular surgery, contact lens wear, use of topical ocular medications, ocular exposure to toxins or irritants, and underlying inflammatory or dermatological disorders.[3][4] Medications implicated in the development of AWE include topical antiglaucoma agents, 5-fluorouracil, topical acyclovir, contact lens solutions, mitomycin C, and interferon.[5] Associated systemic or ocular disease processes comprise ocular cicatricial pemphigoid, acne rosacea, and atopic dermatitis.

The underlying mechanism of AWE remains poorly understood and is likely multifaceted. D’Aversa et al, who first described the condition, proposed that AWE may arise from abnormal parakeratotic limbal epithelial stem cells that proliferate and migrate onto the cornea, producing the characteristic wavelike epithelial pattern. This process resembles partial limbal stem cell deficiency (LSCD) or dysfunction, supporting the hypothesis that these conditions may share similar pathogenic mechanisms. Patients with LSCD present with blurry vision and corneal irritation.[7] LSCD frequently exhibits epitheliopathy originating from the involved limbus, most commonly superior, mirroring the clinical presentation of AWE.[8][9][10] LSCD may develop in response to comparable inciting factors, including ocular trauma, surgery, contact lens wear, and topical antiglaucoma medications.[11][12]

Histopathologic evaluation demonstrates unremarkable corneal epithelium on hematoxylin and eosin staining. Epithelial dysplasia is absent in the histological examination of debrided epithelium specimens. Full-thickness biopsy findings reveal parakeratosis of the conjunctival epithelium with underlying focal mononuclear cell infiltrates that may compress or extend into the overlying epithelium. A study also demonstrated a reduction in the subepithelial nerve plexus compared with healthy control eyes.

Patients with AWE typically present with decreased visual acuity that may progress over months to years or recur after periods of remission. Common symptoms include foreign body sensation, tearing, redness, and ocular irritation, although small lesions or those outside the visual axis may be asymptomatic. A history of ocular surgery or trauma, use of topical ocular medications, and associated conditions such as atopic dermatitis or acne rosacea have been linked to disease development. Slit-lamp examination with fluorescein staining, combined with confocal microscopy, establishes the diagnosis and demonstrates characteristic findings. Spectral-domain optical coherence tomography (OCT) has also been utilized to evaluate the morphology of the palisades of Vogt in AWE. Detailed descriptions of these examination findings are provided in the Evaluation section.

The diagnosis of AWE is established clinically using slit-lamp examination and confocal microscopy. Slit-lamp evaluation characteristically reveals a well-demarcated, centripetally advancing wave of coarse corneal epithelium, most commonly arising from the superior limbus. Sclerotic scatter highlights a granular epithelial texture with sharply defined lesion margins (see Image. Advancing Wavelike Epitheliopathy on Slit Lamp Examination). A subepithelial haze may be present without discrete opacities or infiltrates in the affected areas (see Image. Subepithelial Haze on Slit Lamp Examination). Quadrants of limbal involvement may also be identified with slit-lamp biomicroscopy. Fluorescein staining demonstrates a punctate pattern with well-defined borders. Confocal microscopy reveals atypical, elongated epithelial cells oriented centripetally, with hyperreflective nuclei, an increased nuclear-to-cytoplasmic ratio, and loss of visible cellular borders within the basal epithelium. Spectral-domain OCT has been used to evaluate the microstructure of the palisades of Vogt and further characterize limbal involvement in AWE. Findings include decreased epithelial thickness, loss of the normal sharp stromal tip of the palisades of Vogt, disruption of the smooth epithelial–stromal interface, dilated stromal vessels, and reduced palisade density.[13] These observations suggest that limbal involvement in AWE may extend beyond the epithelium to include the underlying stroma and vessels of the palisades of Vogt.

The accepted course of treatment for AWE involves elimination of potential offending agents, mechanical debridement of abnormal corneal epithelium, and empiric application of a 1% silver nitrate solution to the superior corneoscleral limbus. Most sterile compounding pharmacies can formulate this solution, as it is not available premade for ophthalmic use. For treatment, the affected eye is anesthetized with proparacaine, and a cotton applicator saturated with 1% silver nitrate solution is applied in a rolling fashion to the affected area. The area is flushed with saline, a bandage contact lens is placed, and a 1-week course of topical antibiotics is prescribed. The bandage lens may be removed after 3 to 4 days, following complete epithelialization of the cornea. Symptoms generally resolve within 2 weeks, with replacement of abnormal, irregular epithelium by normal-appearing tissue. Most patients achieve full return of vision, although mild, permanent reductions in visual acuity may persist in some cases. When AWE is asymptomatic, removal of the causative agent alone may suffice for resolution. Silver nitrate is thought to act through cytological mechanisms, inducing apoptosis or chemical alteration of abnormal limbal stem cells responsible for the pathology. Liquid nitrogen cryotherapy has been reported in a single case as an alternative to silver nitrate, producing comparable results. Corneal epithelial debridement enables more complete treatment of the epitheliopathy and more rapid symptom resolution. Debridement alone provides temporary relief but is almost universally followed by recurrence and the need for repeat treatment after several months. These observations support the hypothesis that abnormal limbal stem cells constitute the source of the pathology and must be targeted for complete resolution. Silver nitrate and cryotherapy appear to fulfill this role.

Corneal epithelial debridement enables more complete treatment of the epitheliopathy and more rapid symptom resolution. Debridement alone provides temporary relief but is almost universally followed by recurrence and the need for repeat treatment after several months. These observations support the hypothesis that abnormal limbal stem cells constitute the source of the pathology and must be targeted for complete resolution. Silver nitrate and cryotherapy appear to fulfill this role. Conservative therapies, including artificial tears and topical steroids, may be used initially but have demonstrated limited efficacy in patients with AWE, with most patients exhibiting no improvement. In reported cases, topical steroid use was discontinued due to increased intraocular pressure. One case reported success using fluorometholone eye drops (1 mg/ml) every 8 hours in combination with preservative-free artificial tears every 2 hours until complete resolution. Hypertonic saline solution, topical antibiotics, and therapeutic contact lenses have similarly shown minimal or no benefit in treating AWE. Similarities between AWE and partial LSCD suggest that medical therapies effective in the latter could potentially be applied to the former. These therapies include topical retinoids, topical cyclosporine, autologous topical serum drops, and interferon α2b.[14][15] These treatments have not yet been validated for AWE and require clinical trials for confirmation.

Several ocular conditions can present with features similar to AWE but may be distinguished or excluded based on clinical examination and response to therapy. These conditions include the following: Corneal intraepithelial neoplasia Corneal epithelial dysplasia Squamous cell carcinoma Carcinoma in situ Hereditary benign intraepithelial dyskeratosis Corneal pannus Corneal epithelial keratinization Contact lens–induced keratopathy Superior limbic keratoconjunctivitis Prominent epithelial basement membrane dystrophy Whorled microcystic dystrophy Underlying dermatologic or inflammatory disorders Migratory serpiginous corneal epitheliopathy [16][17][18] Precise recognition of AWE allows clinicians to implement the recommended management strategies effectively. Early and accurate diagnosis reduces the risk of mismanagement and enhances long-term visual outcomes.

The majority of cases respond well to silver nitrate, with restoration of baseline vision. However, mild permanent vision loss may occur rarely. Small patches of irregular epithelium may persist after treatment, but remnants are almost exclusively confined to the corneal periphery, leaving the visual axis clear. Recurrence is uncommon and generally less severe, typically occurring outside the visual axis without necessitating repeat treatment.

Complications are rare and may include corneal abrasion or incomplete resolution, which may necessitate additional treatment. Symptoms may recur. One case demonstrated recurrence on the contralateral side 2 years after the initial presentation.

Patients diagnosed with AWE should identify potential triggers and avoid these exposures whenever possible. Individuals who wear contact lenses need regular cleaning of these devices and should avoid prolonged use. Switching to a hydrogen peroxide–based solution may be considered if a multipurpose contact lens solution is suspected as a contributing factor.

Important points to remember in the evaluation and management of AWE include the following: AWE is a chronic or recurrent corneal disorder characterized by progressive visual impairment, frequently accompanied by ocular irritation or discomfort. The condition most commonly presents after age 40 years and is often associated with prior ocular trauma or surgery, use of topical ocular medications, atopic dermatitis, or acne rosacea. Diagnosis of AWE is primarily clinical, based on slit-lamp examination and confocal microscopy. Histopathology, confocal microscopy, and spectral-domain OCT may provide supportive evidence but are not required for diagnosis. Management typically involves topical application of 1% silver nitrate, with most cases resolving within 2 to 3 weeks after a single treatment. Effective prevention of AWE requires vigilance in identifying individual risk factors and avoiding exposures that may promote epithelial pathology. Adherence to ocular hygiene and regular ophthalmic follow-up reduces the likelihood of recurrence.

Individuals with AWE may initially present to primary care providers with ocular irritation or visual disturbances. Artificial tears can provide symptomatic relief of discomfort or irritation. Patients with confirmed decreases in visual acuity, a history of topical ocular medication use, or symptoms unresponsive to conservative treatment should be referred to an ophthalmologist. Optometrists and pharmacists contribute significantly to patient education and ongoing care.