Interaction of genetic susceptibility and sunlight exposure on primary open-angle glaucoma risk and progression

PURPOSE: To investigate the role of sunlight exposure and its interaction with genetic susceptibility in primary open-angle glaucoma (POAG). METHODS: Among 63 343 participants in the Taiwan Precision Medicine Initiative project who visited Taichung Veterans General Hospital, patients with POAG were identified and controls were matched 1:4 by sex, age and index year. Solar insolation at 6 months before glaucoma diagnosis was estimated from residential data using Quantum Geographic Information System. Genotyping was performed and polygenic risk scores (PRS; PGS004766) were calculated. Optical coherence tomography and standard automated perimetry were performed; retinal nerve fibre layer (RNFL) and mean deviation slopes were estimated. Logistic regression and linear mixed models assessed the effects of sunlight exposure and genetic susceptibility on the risk and progression rate of POAG. Mediation analysis assessed whether intraocular pressure (IOP) mediated the effect of sunlight exposure on POAG. RESULTS: We included 745 participants (mean age 52.0 ±14.2 years; 49% male). After adjusting for age, sex, IOP, comorbidities, urbanisation level and PRS, sunlight exposure significantly associated with greater POAG risk (adjusted OR: 1.20; 95% CI 1.05 to 1.38, p=0.009). Among high-sunlight exposure individuals, POAG proportion increased from 17% to 36% across PRS quartiles (p<0.001); in contrast, no trend was seen in the low-sunlight exposure group. Greater sunlight exposure correlated with faster RNFL thinning (β=-0.09, 95% CI -0.17 to -0.01; p=0.026). Mediation analysis showed that the association between sunlight exposure and POAG was not mediated by IOP (p=0.728). CONCLUSION: Greater sunlight exposure was modestly associated with higher POAG risk and faster progression independent of IOP, particularly among genetically susceptible individuals.