Herpes simplex keratitis resistance to antiviral treatment presents a growing concern. The herpes simplex virus has many different mechanisms of resistance to antiviral treatment, which have been well described. Resistance to acyclovir occurs because of mutations in the viral thymidylate kinase and DNA polymerase that decrease this enzyme's affinity for its substrate. This article discusses factors that explain the prevalence of this resistance, the ability for recurrences in immunocompromised populations, current treatments for acyclovir-resistant herpes simplex keratitis, and novel therapies for this growing concern.

Herpes endotheliitis is a less common manifestation of herpes keratitis, and characteristic examination findings include corneal edema and the presence of keratic precipitates. Infection may be primary or secondary to herpes virus reactivation following exposure to a potential trigger such as physiologic stress or environmental factors. Ocular surgery, including laser-assisted in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK), can trigger reactivation in patients with or without a documented history of previous herpes infection. We present two patients with visually insignificant stromal scarring who denied a previous history of herpetic disease and developed herpes endotheliitis following LASIK and PRK. We demonstrate the importance of an appropriately thorough preoperative evaluation and further workup of any corneal abnormalities, even if such findings initially appear inconsequential.