Topical Spironolactone in Ocular Graft-versus-Host Disease

Ocular graft-versus-host disease (oGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation that causes chronic inflammation, fibrosis, and dysfunction across multiple ocular tissues, including the lacrimal glands, cornea, conjunctiva, and meibomian glands. Common symptoms such as dryness, visual disturbances, and ocular discomfort are often resistant to standard treatment. Current therapies provide partial relief, rarely reverse structural damage, and typically target a limited range of immune or fibrotic pathways. Spironolactone, a mineralocorticoid receptor antagonist, has emerged as a promising candidate due to its ability to block pathological mineralocorticoid signaling. This pathway becomes abnormally active in ocular tissues with low levels of the enzyme 11β-hydroxysteroid dehydrogenase type 2, leading to unchecked inflammation and tissue remodeling. This review outlines the immunopathology of oGVHD in four key anatomical sites and evaluates spironolactone’s potential effects. In the lacrimal glands, spironolactone reduces inflammatory cytokines, limits fibroblast activation, and helps preserve tear production. In the cornea and conjunctiva, it supports epithelial barrier integrity, reduces surface inflammation and fibrosis, and enhances healing. In the meibomian glands, it improves lipid secretion and prevents glandular dropout. Preclinical and early clinical studies show that topical spironolactone improves both objective markers, such as corneal fluorescein staining and lid margin health, and subjective symptoms, with minimal side effects. Spironolactone’s anti-inflammatory, antifibrotic, lipid-enhancing, and epithelial-protective properties position it as a potential disease-modifying therapy for oGVHD. While additional studies are needed to confirm its protective role and long-term efficacy, current evidence suggests that spironolactone may address important unmet needs in the management of this complex condition.