GLP-1 Receptor Agonists Show Dual Ocular Surface Effects: Restoration of Lacrimal-Corneal Axis and Periocular Remodeling

While glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for diabetes mellitus and obesity, reviews of their ocular effects often focus on the posterior segment, neglecting the anterior. The ocular surface, comprising the lacrimal gland, tear film, conjunctiva, meibomian glands, cornea, and periocular tissues, is crucial for vision and comfort. Understanding GLP-1RA impact here is vital, as conditions like dry eye disease affect millions, and current treatments often fall short. This review addresses the gap by framing the ocular surface as a metabolic unit, exploring GLP-1RA involvement in both restoration and remodeling.

This narrative review synthesized existing preclinical and human evidence regarding GLP-1RA effects on the ocular surface. The authors proposed a novel 'metabolic surface unit' concept, encompassing the lacrimal gland, tear film, conjunctiva, meibomian glands, corneal epithelium, corneal nerves, and periocular tissues. They systematically analyzed studies, categorizing findings into two primary themes: biologic restoration of the lacrimal-corneal-neural axis and structural remodeling of the periocular region. The review critically assessed both the mechanistic rationale from animal models and the observational and limited clinical data from human cohorts.

Preclinical studies provide a strong biologic rationale for GLP-1RA benefits. Liraglutide has been shown to reduce lacrimal gland inflammation and fibrosis, improve tear secretion, enhance corneal epithelial migration, and promote nerve regeneration. A study using semaglutide in aged mice indicated lacrimal structural rescue through attenuation of senescence-associated inflammatory, oxidative, and fibrotic programs. Human evidence, though largely observational, supports some positive effects. Retrospective diabetic cohorts demonstrated lower rates of dry eye disease and superficial keratitis in GLP-1RA users. A small clinical study reported better Schirmer testing and tear breakup time in individuals on GLP-1RAs. > However, emerging oculoplastic and imaging studies, particularly in obesity and weight loss populations, suggest potential periocular volume loss, brow descent, and dermatochalasis, which could alter lid support, blink mechanics, and tear distribution. This dual effect highlights both restorative and remodeling aspects.