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

Abstract

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 dose reduction of immunosuppressive therapy are useful adjuncts. Importance: Clinicians should consider performing epithelial debridement in recalcitrant HK, allowing geno- and phenotypically guided therapy. 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, only 2 cases of proven ACV resistant HK treated with topical foscarnet have been published before.Furthermore, this paper highlights a lack of controlled studies investigating alternative topical treatments in case of viral resistance, offering opportunities for future research.

Keywords

• Herpetic keratitis
• Acyclovir resistance
• Foscarnet
• Thymidine kinase