Association of leucocyte telomere length with incident age-related macular degeneration: a prospective UK Biobank Study.

Purpose: There have been conflicting findings on the role of leucocyte telomere length (LTL) in the risk of age-related macular degeneration (AMD). In this study, we evaluated the associations between LTL and the risk of incident AMD and explored whether age, sex and/or genetic predisposition to AMD can modify these associations.

Methods: We conducted a longitudinal cohort study involving 332 123 AMD-free participants with complete baseline covariates and LTL data from the UK Biobank. We employed multivariable Cox proportional hazards models to test the association between LTL and AMD incidence, estimating the HRs and 95% CIs. Genetic risk was assessed using polygenic risk score (PRS).

Results: During a median follow-up of 13.63 years, 6754 participants (2.03%) developed AMD. Shorter LTL was not associated with incident AMD risk (HR=1.042, 95% CI: 0.992 to 1.094; p=0.10) after adjusting for multiple confounders. Sex showed an interactive effect with LTL (p=0.01 for interaction) on incident AMD risk, while age and PRS did not modify these associations. We identified a significant association between shorter LTL and incident AMD risk in females (HR=1.093, 95% CI: 1.025 to 1.166; p=0.007), but not in males. Moreover, shorter LTL was associated with thinner photoreceptor segments only in females at both baseline and repeated assessments (β=-0.141 µm, 95% CI: -0.267 to -0.016; β=-0.345 µm, 95% CI: -0.649 to -0.041, p<0.05).

Conclusions: Shorter LTL increased the risk of incident AMD in females, suggesting LTL as a potential biomarker for AMD development with sex-specific function.