Natural History and Progression of Untreated Keratoconus: An Updated Systematic Review and Meta-Analysis

To perform an updated systematic review and meta-analysis of the natural history of untreated keratoconus by incorporating advanced diagnostic parameters and extended follow-up periods.

We searched PubMed, Embase, Web of Science, Scopus from inception to September 25, 2025. Eligible studies followed untreated keratoconus eyes for ≥6 months and reported longitudinal changes in conventional and/or advanced progression metrics. Outcomes were pooled using random-effects models. Subgroup analyses and meta-regression were performed to explore heterogeneity and identify predictors of progression.

Ninety-two studies encompassing 30,342 untreated keratoconus eyes were included; 47 studies were eligible for meta-analysis. A significant progressive increase in maximum keratometry (Kmax) was observed over time (mean change: 0.28 D at <12 months, 0.62 D at 12 months, and 1.21 D at >12 months; all p < .05). Mean keratometry (Kmean), steep keratometry, flat keratometry, and thinnest corneal thickness also showed significant deterioration beyond 12 months. Meta-regression demonstrated that younger age and higher baseline Kmean predicted greater Kmax progression; in Pentacam-based analyses, each 1-D increase in baseline Kmean predicted a 0.54-D increase in Kmax at 12 months (p < .001), while each 10-year increase in age reduced Kmax progression by 1.46 D (p < .001).

Untreated keratoconus shows time-dependent progression, with younger age and steeper baseline Kmean associated with faster worsening. Compared with Kmax, baseline Kmean may be a more reproducible predictor of subsequent progression. A multidimensional monitoring approach incorporating both conventional and advanced metrics may improve risk stratification and support timely intervention.