Identification of risk factors for the progression of age-related macular degeneration: a systematic review and meta-analysis of cohort studies

Abstract

Background: Age-related macular degeneration (AMD) is a retinal degenerative disease that primarily affects the elderly population and is a leading cause of vision loss in older adults. There is a lack of research comprehensively examining the risk factors for AMD progression. This study aimed to identify the risk factors influencing the development of AMD using a meta-analysis approach.

Methods: We systematically searched the PubMed, Embase, and Cochrane Library databases from their inception until November 2024. Summary effect estimates were assigned as odds ratios (ORs) with 95% confidence intervals (CIs) using a random effects model. Further exploratory analyses included sensitivity and sub-group analyses.

Results: Eighteen cohort studies involving 38,697 individuals were included in the final meta-analysis. We noted male versus female was associated with a reduced risk of AMD (OR: 0.84; 95% CI: 0.72-0.98; p = 0.027). The identified risk factors for AMD included per 5-year increment in age (OR: 1.14; 95% CI: 1.09-1.19; p < 0.001), current smoking (OR: 1.28; 95% CI: 1.07-1.52; p = 0.007), alcohol intake (OR: 1.30; 95% CI: 1.00-1.67; p = 0.046), per 1 mmol/L increment in high-density lipoprotein (OR: 1.21; 95% CI: 1.08-1.36; p = 0.001), total drusen >10% of the grid (OR: 7.85; 95% CI: 4.66-13.23; p < 0.001), presence of depigmentation (OR: 6.39; 95% CI: 2.48-16.44; p < 0.001), presence of hyperpigmentation (OR: 6.03; 95% CI: 1.94-18.73; p = 0.002), and >10 small drusen (OR: 7.21; 95% CI: 2.10-24.72; p = 0.002).

Conclusion: This study systematically identified the risk factors for AMD progression, and exploratory analyses were performed to determine the risk factors for early and late AMD. Patients at high risk of AMD should be monitored to improve modifiable risk factors and slow the progression of AMD.

Systematic review registration: INPLASY platform (INPLASY2024120036).

Keywords: age-related macular degeneration; meta-analysis; progression; risk factors; systematic review.

Figure 1

Flow diagram of the literature search and trial selection process.

Figure 2

Association of sex, age, and body mass index (BMI) with the risk of age-related macular degeneration (AMD).

Figure 3

Association of smoking and alcohol intake with the risk of age-related macular degeneration (AMD).

Figure 4

Association of hypertension and diabetes mellitus (DM) with the risk of age-related macular degeneration (AMD).

Figure 5

Association of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride (TG) levels with the risk of age-related macular degeneration (AMD).

Figure 6

Association of cardiovascular disease (CVD), stroke, dyslipidemia, C-reactive protein (CRP), formal education, and low socioeconomic status with the risk of age-related macular degeneration (AMD).

Figure 7

Association of total drusen >10% of the grid, presence of depigmentation, presence of hyperpigmentation, and >10 small drusens, and refractive error with the risk of age-related macular degeneration (AMD).