Rationale: Herpes simplex virus 1 establishes a latent infection in trigeminal ganglia. Reactivation causes cold sores, as well as viral keratitis. The purpose of this study was to report potential benefits of using active vitamin D receptor ligands (VDR-agonists) as adjunctive therapies for the treatment of infectious corneal perforations, and prevention of HSV recurrence. Patient concerns: A 57-year-old female with a past history of episodic, poorly-healing, corneal erosions, recurring orolabial herpetic lesions, as well as PCR-confirmed recurrences of herpes simplex keratitis presented with a burning sensation and slight pain in the right eye. Examination indicated HSV keratitis. Topical antibiotic and oral antiviral treatments were prescribed. Despite these standard-of-care treatments, a perforated corneal ulcer ensued. Diagnoses: Corneal perforation associated with HSV-1 keratitis recurrence, later confirmed by PCR analysis of corneal scrapings. Interventions: Corneal perforation was treated with a human fibrin glue, fortified with multilayered amniotic membrane transplant, as well as a therapeutical contact lens. Following surgery, calcifediol and paricalcitol were started as oral adjunctive therapies in an attempt to boost tissue regeneration and innate-immunity within the slow-healing cornea. Anterior segment optical-coherence tomography was used to measure corneal thickness. Frequent follow-ups with various specialists allowed for comprehensive patient evaluation, and meticulous screening for any signs indicating potential HSV-1 recurrence. Outcomes: Following calcifediol-paricalcitol therapy corneal thickening, and re-epithelization ensued. During combined calcifediol-paricalcitol therapy, the patient has had no recurrence of herpes simplex keratitis, or orolabial herpes lesions. Lessons: Corneal stabilization avoided a high-risk, full-thickness corneal transplantation, facilitating future cataract surgery, and allowing for some degree of visual recovery in this eye. Export