Potential Harms of Ocular and Periorbital Topical Vitamin A Application: A Systematic Review and Meta-Analysis

Purpose: Topical vitamin A derivatives (retinoids) are widely used for dermatologic and cosmetic indications and are often applied to the face and periorbital region. Although vitamin A is essential for epithelial integrity and tear film homeostasis, concerns exist regarding potential adverse effects on the ocular surface and meibomian glands. This systematic review and meta-analysis evaluated ophthalmic and periorbital harms associated with topical vitamin A products. Methods: PubMed, Web of Science, Scopus, and the Cochrane Library were searched from inception to August 25, 2025, following PRISMA guidelines (PROSPERO CRD42024523189). Randomized and nonrandomized human studies evaluating topical vitamin A products applied to the ocular surface or periorbital region were included. Studies were independently screened, data were extracted, and risk of bias was assessed by two reviewers. Dichotomous harms were pooled using Peto fixed-effects odds ratios (ORs) with 95% confidence intervals (CIs). Results: Eighty-nine studies (10,794 participants) met inclusion criteria; 55 were included in meta-analysis. Compared with controls, topical vitamin A derivatives increased odds of pain (OR = 6.37), dryness (OR = 2.69), burning (OR = 2.44), and any harm (OR = 1.71). Serious adverse events were uncommon and not significantly increased (OR = 1.21). Prescription-strength products showed higher odds of harm, and non-prescription formulations were not significantly associated with increased harms. Evidence certainty ranged from very low to low. Conclusions: Topical vitamin A products applied to the ocular or periorbital region are associated with increased ocular discomfort and surface-related harms, particularly with prescription-strength formulations, with important implications for dry eye and meibomian gland dysfunction management.