Sungsoon Hwang MD ^1,2, Se Woong Kang MD, PhD ¹, Sang Jin Kim MD, PhD ¹, Kyungdo Han PhD ³, Bong Sung Kim MS ³, Wonyoung Jung MD ⁴, Dong Hui Lim MD, PhD ^{1,2 ∗}, Dong Wook Shin MD, PhD ^{2,4 ∗}

¹Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
²Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea
³Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
⁴Department of Family Medicine and Supportive Care Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

Correspondence: Dong Hui Lim, MD, PhD, Dong Wook Shin MD, PhD

Purpose: To evaluate the prospective association of age-related macular degeneration (AMD) and related visual disability (VD) with the risk of depression.

Design: This nationwide population-based cohort study used authorized clinical data provided by the Korean National Health Insurance Service.

Participants: A total of 3,599,589 individuals over 50 years of age participated in the Korean National Health Screening Program in 2009.

Methods: AMD diagnosis and the presence of accompanying VD were verified using diagnostic codes and disability registration data. Data on covariates, including age, sex, income level, residential area, systemic comorbidities, and behavioral factors, were collected from health screening results and claims data. Patients were followed until December 2019, and incident cases of depression were identified using registered diagnostic codes. The prospective association of AMD and related VD with new-onset depression was investigated using the multivariable-adjusted Cox proportional hazard model.

Main outcome measures: Hazard ratios and 95% confidence intervals for depression development according to the presence of AMD and VD.

Results: During an average follow-up period of 8.52 years, 1,037,088 patients were newly diagnosed with depression. Patients previously diagnosed with AMD had a greater risk of new-onset depression, with a hazard ratio (95% confidence interval) of 1.15 (1.13-1.17), compared to the control group in the fully adjusted model. Patients with AMD and accompanying VD had a further increased risk of depression, with a hazard ratio (95% confidence interval) of 1.23 (1.16-1.30).

Conclusions: Individuals diagnosed with AMD have a higher risk of developing depression in the future. The risk of depression is further increased in AMD patients with VD.