Active Vitamin D Receptor Agonists As Adjunctive Therapies For Infectious Keratitis And Corneal Perforation: Case Report

Herpes simplex virus 1 (HSV-1) a neurotropic virus, that establishes a latent infection in trigeminal ganglia. Reactivation causes cold sores, as well as viral keratitis. Recurrent viral keratitis can lead to progressive corneal scarring and, in rare cases, corneal perforation. Recent studies suggest vitamin D receptor agonists promote corneal wound healing by reducing production of proinflammatory cytokines, and matrix-metalloproteinases, a key enzymes for collagen degradation in infectious keratitis. Purpose of this study is to report a case where a combination of two vitamin D receptor agonists, calcifediol and paricalcitol was used as an adjunctive therapy to improve corneal perforation healing, and reduce the risk of HSV-1 recurrence.

A 57-year-old female, with a past history of episodic, poorly-healing, corneal erosions, recurring orolabial Herpes, as well as Herpes simplex keratitis, presented with burning sensation and slight pain in the right eye. Examination indicated infectious keratitis. Topical antibiotic and oral antiviral treatments were prescribed. Despite these standard-of-care treatments, a perforated corneal ulcer ensued.

The perforated cornea was treated with a multilayered, amniotic membrane transplant, fortified with cyanoacrylate glue, compression, as well as a therapeutical contact lens. The perforation closed following a complete absorption of the amniotic membrane transplant. Calcifediol (10 µg, twice daily) and paricalcitol (1µg, every other day) were started as adjunctive therapies, in an attempt to boost innate-immunity and tissue regeneration within the slow-healing cornea.

Corneal perforation healing and re-epithelialization improved significantly after the initiation of the combined Vitamin D receptor agonist therapy (calcifediol + paricalcitol). During combined calcifediol-paricalcitol therapy, the patient has had no reoccurrence of Herpes simplex keratitis, or orolabial Herpes lesions. This case highlights potential benefits of using active Vitamin D Receptor agonists as adjunctive therapies for the treatment of infectious corneal perforations.

With the increasing number of studies linking Vitamin D Receptors to improved corneal wound healing, topical or oral application of the inactive nutrient, Vitamin D3 (cholecalciferol), as well as active Vitamin D receptor agonists (calcifediol (25D3), calcitriol (1,25D3), paricalcitol (1,25D2), should be considered as possible adjunctive therapies. We suspect that Vitamin D receptor agonists, such as calcifediol and paricalcitol, could potentially replace the antibiotic doxycycline as a common adjunctive therapy in treating infectious corneal ulcers, and perforations. Further research is required to elucidate the physiological actions of Vitamin D receptor agonists on the cornea, and to determine required dosages for optimal results.