Purpose: We explored whether risk factor associations differed by primary open-angle glaucoma (POAG) subtypes defined by visual field (VF) loss pattern (i.e., paracentral or peripheral).
Methods: We included 77,157 women in the Nurses' Health Study (NHS) and 42,773 men in the Health Professionals Follow-up Study (HPFS 1986-2010), and incident medical record confirmed cases of paracentral (n = 440) and peripheral (n = 865) POAG subtypes. We evaluated African heritage, glaucoma family history, body mass index (BMI), mean arterial blood pressure, diabetes mellitus, physical activity, smoking, caffeine intake, and alcohol intake. We used competing risk Cox regression analyses modeling age as the metameter and stratified by age, cohort, and event type. We sequentially identified factors with the least significant differences in associations with POAG subtypes ("stepwise down" approach with P for heterogeneity [P-het] < 0.10 as threshold).
Results: Body mass index was more inversely associated with the POAG paracentral VF loss subtype than the peripheral VF loss subtype (per 10 kg/m2; hazard ratio [HR] = 0.67 [95% confidence interval (CI): 0.52, 0.86] versus HR = 0.93 [95% CI: 0.78, 1.10]; P-het = 0.03) as was smoking (per 10 pack-years; HR = 0.92 [95% CI: 0.87, 0.98] versus HR = 0.98 [95% CI: 0.94, 1.01]; P-het = 0.09). These findings were robust in sensitivity analyses using a "stepwise up" approach (identify factors that showed the most significant differences). Nonheterogeneous (P-het > 0.10) adverse associations with both POAG subtypes were observed with glaucoma family history, diabetes, African heritage, greater caffeine intake, and higher mean arterial pressure.
Conclusions: These data indicate that POAG with early paracentral VF loss has distinct as well as common determinants compared with POAG with peripheral VF loss.