Risk factors for keratoconus: a systematic review and meta-analysis

Keratoconus (KC) is a sight-threatening disease with unclear etiology. Understanding its risk factors is essential for prevention and mechanistic insight. This study presents a comprehensive systematic review and meta-analysis to evaluate the factors associated with keratoconus, synthesizing the available evidence. A comprehensive literature search was performed in PubMed, the Cochrane Library, Embase, and Web of Science for studies reporting factors associated with keratoconus, with no restrictions on publication date or language, from inception to September 2025. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. At least two authors used the assessment tools of the Joanna Briggs Institute (JBI) to evaluate the quality of the methodology of the final included studies. Subgroup analysis by region and age was conducted to reduce the heterogeneity among studies. Both quantitative statistical tests (Egger’s and Begg’s tests) and qualitative funnel plots were employed to comprehensively evaluate the existence of publication bias. We identified 33 studies involving 1,537,739 individuals: 21 were case-control studies, 4 were cohort studies, and 8 were cross-sectional. 14 factors included in this analysis and their OR (95% CI) are as follows: family history 8.95(5.24, 15.28), eye rubbing 6.20(4.32, 8.91), allergy 1.68(1.25, 2.26), atopy 1.39(0.90, 2.15), eye allergy 6.40(2.44, 16.73), allergic dermatitis/eczema 1.99(1.34, 2.96), asthma 1.63(1.38, 1.93), allergic rhinitis 1.37(1.12, 1.67), inappropriate sleeping position 5.55(1.35, 22.76), dry eye disease 2.55(1.05, 6.18), obesity 1.40(1.03, 1.88), smoking 0.80(0.65, 0.99), inflammatory bowel disease 1.24(0.95, 1.63), diabetes 0.87(0.69, 1.10). Positive family history, eye rubbing, allergy, allergic dermatitis/eczema, asthma, allergic rhinitis, inappropriate sleeping positions, dry eye disease, and obesity are significantly associated with an increased likelihood of keratoconus, whereas smoking exhibited a protective effect. No significant associations were found between KC and atopy, inflammatory bowel disease, or diabetes. Standardized definitions and severity gradings of these factors are needed to clarify causal mechanisms and inform evidence-based preventive strategies.