BACKGROUND: Aging of the population has resulted in more patients living with atrial fibrillation (AF) and age-related macular degeneration (AMD). AF is associated with macro- and micro-thromboembolism, microvascular dysfunction, and system inflammation. Organ systems sensitive to the long-term systemic and vascular disease associations of AF will likely develop dysfunction over time. There is also an increase in age-related macular degeneration (AMD), which shares many pathophysiologic risk factors of AF. We hypothesized that AF will increase the risk of AMD. METHODS: A total of 38 746 consecutive patients from the large ongoing prospective angiography INSPIRE Study database without a history of AMD were evaluated for the development of AMD. Long-term incidence of AMD was assessed at 1 and 5 years and at last follow-up to determine its association with AF. RESULTS: Over a mean follow-up of 2159.4 ± 1851.7 days, 11 787 (30.4%) had or developed AF. Patients with AF were older (67.7 ± 12.2 vs. 57.5 ± 15.5 years, p <
0.0001), and had higher rates of hypertension (50.0% vs. 44.0%, p <
0.0001), renal failure (1.7% vs. 1.1%, p <
0.0001), stroke (4.6% vs. 3.1%, p <
0.0001), and heart failure (27.3% vs. 11.5%, p <
0.0001). AF patients were more likely to be treated with a statin, ACE/ARB, diuretic, and warfarin. The overall incidence of AMD over the follow-up period was higher in patients with AF (2.1% vs. 1.2%, p <
0.0001). Compared with no AF, the risk of AMD in patients with AF was increased at 1 year (hazard ratio [HR] = 1.92 [1.26-2.93], p = 0.003), 5 years (HR = 1.83 [1.46-2.29], p <
0.0001), and long-term (1.80 [1.52-2.12], p <
0.0001). The association of AF with AMD was attenuated after adjustment by baseline characteristics, comorbidities, and medications. All AMD risks were mitigated in multivariable modeling that included baseline characteristics (i.e., CHA2DS2-Vasc) and drug therapies for AF. CONCLUSION: Patients with AF are at elevated risk of developing AMD that increases over time when compared to patients without AF. In this cohort of patients, the risk of AMD is due to risk factors that drive the presence of AF itself and its progression. Comprehensive treatment of AF that focuses on its underlying risk factors, including dynamic reassessment of risk factors during follow-up, may impact risk of AMD in patients with AF.