Free thyroxine increases the risk of AMD

Abstract

Purpose: Hypothyroidism and thyroid hormone use have previously been linked to age-related macular degeneration (AMD). We investigated the association between thyroid function and the risk of AMD in the large prospective study Rotterdam Study.

Methods: We included participants aged 55 years and older from the Rotterdam Study with free thyroxine (FT4) and/or thyroid-stimulating hormone (TSH) measurements, AMD grading at baseline, and at least one follow-up examination. Using Cox-proportional hazards models, adjusting for sex and age, we explored the association between TSH or FT4 and incident AMD (early and late) in the overall sample and in euthyroid individuals (normal range FT4 [11-25 pmol/L] with normal range TSH [0.4-4.0 ImU/L]). In a multivariable model we additionally adjusted for smoking, diabetes, hypertension, cholesterol, body-mass index and thyroid peroxidase antibodies positivity.

Results: We included 5573 participants with a mean follow-up of 7.6 years (interquartile range [IQR] range of 4.4-10.8 years). A total of 805 people developed incident AMD (Early N= 725, Late N= 80) during follow-up. Cox-proportional hazard analyses showed that higher FT4 levels were associated with an increased risk of AMD; hazard ratio [HR] 1.04 (95% confidence interval [CI] 1.01-1.06). This association remained significant after multivariable adjustments, even in euthyroid participants, (all P < 0.05). Subgroup analyses showed that FT4 was particularly associated with RPE alterations (HR 1.04 [95%CI 1.01-1.07]), and not with drusen type or drusen area. No association was found with TSH.

Conclusions: Our data suggest that higher levels of free thyroxine may be associated with AMD, even in euthyroid individuals. Although in need for confirmation, increased catabolic action affecting RPE function may be a mechanism that explains our findings.