Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis

Abstract

Background: Age-related macular degeneration (AMD) is the leading cause of blindness in Western countries. Numerous risk factors have been reported but the evidence and strength of association is variable. We aimed to identify those risk factors with strong levels of evidence which could be easily assessed by physicians or ophthalmologists to implement preventive interventions or address current behaviours.

Methods: A systematic review identified 18 prospective and cross-sectional studies and 6 case control studies involving 113,780 persons with 17,236 cases of late AMD that included an estimate of the association between late AMD and at least one of 16 pre-selected risk factors. Fixed-effects meta-analyses were conducted for each factor to combine odds ratio (OR) and/or relative risk (RR) outcomes across studies by study design. Overall raw point estimates of each risk factor and associated 95% confidence intervals (CI) were calculated.

Results: Increasing age, current cigarette smoking, previous cataract surgery, and a family history of AMD showed strong and consistent associations with late AMD. Risk factors with moderate and consistent associations were higher body mass index, history of cardiovascular disease, hypertension, and higher plasma fibrinogen. Risk factors with weaker and inconsistent associations were gender, ethnicity, diabetes, iris colour, history of cerebrovascular disease, and serum total and HDL cholesterol and triglyceride levels.

Conclusions: Smoking, previous cataract surgery and a family history of AMD are consistent risk factors for AMD. Cardiovascular risk factors are also associated with AMD. Knowledge of these risk factors that may be easily assessed by physicians and general ophthalmologists may assist in identification and appropriate referral of persons at risk of AMD.

Figure 1

Study selection process.

Figure 2

Prevalence of late AMD by age (adapted from Varma et al[61]and Kawasaki et al[19]).

Figure 3

Pooled odds ratio for late AMD by gender (female vs. male).

Figure 4

Pooled odds ratio for late AMD and by race/ethnicity (whites vs. other races/ethnicities).

Figure 5

Pooled odds ratio for late AMD by family history (presence or absence).

Figure 6

Pooled odds ratio for late AMD by history of previous cataract surgery.

Figure 7

Pooled odds ratio for late AMD by smoking status (current vs. never).

Figure 8

Pooled odds ratio for late AMD by iris color (brown vs. blue eyes).

Figure 9

Pooled odds ratio for late AMD by body mass index (obese vs. non-obese).

Figure 10

Pooled odds ratio for late AMD by hypertension (presence or absence).

Figure 11

Pooled odds ratio for late AMD by diabetes (presence or absence).

Figure 12

Pooled odds ratio for late AMD by cardiovascular disease (presence or absence).

Figure 13

Pooled odds ratio for late AMD by cerebrovascular disease (presence or absence).

Figure 14

Pooled odds ratio for late AMD by plasma fibrinogen.