Genetic Variants in Ciliary Body Development Genes and Their Association with Myopia: A Systematic Review

Numerous genetic variants have been implicated in myopia pathogenesis, yet their biological mechanisms remain unclear. One proposed mechanism is that variants in genes involved in ciliary body development may influence ciliary muscle structure and accommodative function, thereby influencing individual variation in myopia risk. The aim was to systematically evaluate published evidence linking myopia with genetic variants in genes implicated in ciliary body developmental pathways and identify candidate variants for comparison with ciliary muscle properties to validate this mechanistic pathway.

A comprehensive search of existing literature was conducted across PubMed, Embase, CINAHL, Cochrane Library, ProQuest, and Scopus on July 2 2025 and February 25 2026. References and citations of papers considered eligible for inclusion were examined to identify additional papers. Studies were included if they examined the association between myopia and single nucleotide polymorphisms (SNPs) within 1 kb of notch receptor 2 (NOTCH2), catenin beta 1 (CTNNB1), transforming growth factor beta 2 (TGFB2), paired box 6 (PAX6), and bone morphogenetic protein 4 (BMP4). Covidence was used to identify and conduct a narrative synthesis of findings from eligible studies. Quality assessment was performed using adapted versions of the Newcastle-Ottawa Scale.

Twenty-two studies-12 observational studies, five genome-wide association studies (GWAS), and five GWAS meta-analyses-were identified. Observational studies only examined SNPs within 1 kb of TGFB2 and PAX6, with rs7550232 (TGFB2) providing the strongest evidence for an association with myopia. GWAS and GWAS meta-analyses examined SNPs related to all five genes, with rs2953 (CTNNB1) and rs17563 (BMP4) having the most compelling evidence of an association with myopia.

Genetic variants identified in observational studies were distinct from those identified in GWAS and GWAS meta-analyses, which frequently examined overlapping cohorts. Further studies are required to validate these associations and clarify whether these variants influence myopia risk through an underlying mechanism involving ciliary muscle physiology.