Putting drug resistant epithelial herpes keratitis in the spotlight: A case series

PURPOSE: To strengthen the sparse evidence on acyclovir (ACV) resistance, especially in recalcitrant herpetic keratitis (HK), by describing the clinical course of 3 genotypically proven ACV resistant HK cases. An overview of mechanisms of resistance and therapeutic options currently available to ophthalmologists is provided based upon recent literature search. OBSERVATIONS: Resistance to ACV due to known mutations in the gene encoding the viral thymidine kinase was confirmed in 2 cases, and a novel mutation in the UL23 gene (N202K) conferring phenotypical resistance to ACV was discovered in 1 case. Three unique therapeutic strategies finally led to epithelial closure. CONCLUSIONS: The novel thymidine kinase mutation (N202K) should be considered to infer resistance to all molecules requiring activation by the viral thymidine kinase. Current topical alternatives in the ophthalmologist's armamentarium include trifluridine 1%, foscarnet 1,2%-1,4% or cidofovir 0,2–0,5%. Epithelial debridement, high-frequency dosing and reduction of immunosuppression are useful adjuncts. IMPORTANCE: Clinicians should perform epithelial debridement in recalcitrant HK, allowing geno- and phenotypically guided therapy, even without a history of long-term anti-viral prophylaxis or recurrent HK. This report provides mandatory knowledge allowing the reader to comprehend how therapy should be altered based upon these results. To the best of our knowledge, successful treatment of proven ACV resistant HK with topical foscarnet has not yet previously been published. Furthermore, this paper highlights a lack of controlled studies investigating alternative topical treatments in case of viral resistance, offering opportunities for future research.