Drug-induced corneal epithelial changes

Abstract

Drugs across many pharmacologic classes induce corneal epithelial changes. Many of these drugs have cationic amphiphilic structures, with a hydrophobic ring and hydrophilic cationic amine side chain that allow them to cross cell membranes. These drugs lead to intracellular phospholipid accumulation, often manifested in the cornea by vortex keratopathy, with no effect on visual acuity and few ocular symptoms. Other drugs, notably antineoplastic agents, produce a fine diffuse corneal haze, sometimes accompanied by decreased vision that can be dose limiting. Still other medications cause crystalline epithelial precipitation that might require debridement for resolution. An understanding of the variety of drugs involved, the multiple mechanisms responsible, and the systemic diseases that produce similar changes can lead to improved management strategies for patients with corneal epithelial deposits. In most cases, drug therapy need not be modified or discontinued, but if visual acuity is affected, close collaboration with the prescribing physician can result in determining an optimized dose that treats systemic disease and minimizes these deposits. Additionally, close monitoring might be required if the drug is also associated with other ocular findings, such as optic neuropathy or retinopathy.

Once-Daily Netarsudil Versus Twice-Daily Timolol in Patients With Elevated Intraocular Pressure: The Randomized Phase 3 ROCKET-4 Study

“…Cornea verticillata are a common occurrence with amiodarone 30 and other treatments that have been approved by the United States Food and Drug Administration. 29 Cornea verticillata were reported as mild or moderate in all affected ROCKET-4 study participants and were not associated with decreases in visual function; they were only observed at the biomicroscope (ie, patients were asymptomatic and unaware of the presence of cornea verticillata) and resolved following treatment cessation in most (60.5%) affected patients by study end. Conjunctival hemorrhage, which was typically described by investigators as small petechial hemorrhages, was reported as mild or moderate in all cases and generally resolved with continued use of netarsudil.…”

“…They form through a process known as phospholipidosis, which occurs when cationic amphiphilic drugs such as netarsudil complex with lysosomal phospholipids. [27][28][29] They are a result of the chemical properties of the drug and are not metabolic in nature. Cornea verticillata are a common occurrence with amiodarone 30 and other treatments that have been approved by the United States Food and Drug Administration.…”

Netarsudil/Latanoprost Fixed-Dose Combination for Elevated Intraocular Pressure: Three-Month Data from a Randomized Phase 3 Trial

“…Cornea verticillata forms through a process known as phospholipidosis, which occurs when cationic amphiphilic drugs like netarsudil bind to lysosomal phospholipids. [32][33][34] The development of cornea verticillata is associated with systemic amiodarone and other U.S. Food and Drug Administration-approved drugs, including subconjunctival gentamicin and tobramycin. It is typically asymptomatic, with no apparent effect on visual function, and generally resolves after treatment discontinuation.…”

Quantitative evaluation of visual function in patients with cornea verticillata associated with Fabry disease

“…Among these, cornea verticillata (occasionally described as vortex keratopathy) is the most distinctive and prevalent clinical feature (Raizman et al. ). It is shown to be present in both hemizygous men and heterozygous women.…”