THE ROLE OF INFLAMMATION IN KERATOCONUS: AN UPDATED REVIEW OF CURRENT EVIDENCE

Background: Keratoconus is a progressive corneal ectatic disorder characterized by stromal thinning, anterior corneal protrusion, irregular astigmatism, and gradual visual deterioration. Although it has traditionally been considered a non-inflammatory disease, increasing molecular, genetic, and clinical evidence suggests that chronic low-grade inflammation may contribute to its development and progression. Objective: This narrative review aims to summarize current evidence on the role of inflammation in keratoconus, with emphasis on tear-film cytokines, matrix metalloproteinases, oxidative stress, genetic susceptibility, environmental triggers, inflammatory biomarkers, and emerging therapeutic implications. Methods: A narrative literature review was conducted using relevant peer-reviewed articles from major scientific databases. Evidence was synthesized thematically to discuss inflammatory mechanisms, molecular pathways, ocular surface factors, clinical implications, and future directions in keratoconus research and management. Main Findings: Current evidence indicates that patients with keratoconus may show increased levels of inflammatory mediators, including interleukin-1β, interleukin-6, tumor necrosis factor-alpha, high-mobility group box 1, and matrix metalloproteinases. These mediators may contribute to extracellular matrix degradation, keratocyte dysfunction, stromal thinning, and progressive corneal weakening. Oxidative stress, cellular senescence, allergy, atopy, dry eye disease, and habitual eye rubbing may further amplify inflammatory activity at the ocular surface. Recent genetic and molecular studies also suggest that keratoconus susceptibility may involve both biomechanical and atopy–inflammatory pathways. Corneal collagen cross-linking remains the established treatment for progressive disease, while anti-inflammatory, exosome-based, intense pulsed light, and nutritional approaches remain supportive or investigational. Conclusion: Keratoconus should not be viewed as a purely biomechanical disorder. Current evidence supports a broader inflammatory-degenerative model in which inflammation, oxidative stress, genetic susceptibility, ocular surface disease, and environmental factors interact to influence disease progression. Further longitudinal studies, standardized biomarker validation, and controlled clinical trials are needed before inflammatory markers or emerging therapies can be incorporated into routine keratoconus care. Keywords: Keratoconus; inflammation; tear-film biomarkers; cytokines; matrix metalloproteinases; oxidative stress; eye rubbing; corneal collagen cross-linking