Alterations of the ocular surface during diabetes: molecular mechanisms and therapeutic strategies.

BACKGROUND

Chronic hyperglycemia disrupts ocular surface homeostasis through oxidative stress, inflammation, autonomic neuropathy, and microvascular damage. These alterations contribute to dry eye disease, conjunctival changes, and corneal neuropathy, yet the underlying mechanisms are not fully understood. This review explores the molecular, cellular, and physiological pathways involved in diabetes-related ocular surface damage and summarizes current and emerging therapeutic approaches.

METHODS

A narrative review of peer-reviewed literature was performed, integrating clinical, histological, and molecular findings on conjunctival alterations, tear film dysfunction, oxidative stress, microbiota changes, and corneal nerve impairment in diabetic patients. Both established treatments and therapies under clinical or preclinical development were examined.

RESULTS

Hyperglycemia induces the accumulation of advanced glycation end-products, activates RAGE signaling, and increases ROS production, leading to endothelial dysfunction, goblet cell loss, and epithelial barrier compromise. Tear film instability results from lacrimal gland microvascular injury, Meibomian gland dysfunction, and reduced corneal sensitivity secondary to neuropathy. Corneal neuropathy-marked by reduced sub-basal nerve density, nerve tortuosity, punctate keratitis, and delayed healing-affects up to 70% of patients and may precede diabetic retinopathy. Treatments include lubricants, autologous serum, topical insulin, amniotic membranes, and tarsorrhaphy. Promising experimental therapies include neurotrophic factors, α-lipoic acid, PEDF, resolvins, GLP-1-based agents, and gene-based strategies.

CONCLUSION

Diabetes profoundly impacts the ocular surface through oxidative, inflammatory, neurogenic, and microvascular mechanisms that compromise tear film stability and corneal health. Early detection and targeted management are crucial to prevent progression to neurotrophic keratopathy. Further research is needed to refine mechanism-driven therapies.

© 2025. The Author(s), under exclusive licence to Springer Nature B.V.