Comparison of Risk Factor Profiles for Primary Open-Angle Glaucoma Subtypes Defined by Pattern of Visual Field Loss: A Prospective Study

Abstract

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.

Figure

Paracentral and peripheral visual field loss definitions. A representative pattern deviation (PD) plot used to define the type of VF loss for the left eye is depicted. The different boxed areas represent the various regions that can show glaucomatous VF defects; defects were defined as ≥3 contiguous points that are <−5 decibels. The box with a dashed line indicates the paracentral region in the superior hemifield (the mirror-image region below the horizontal line indicates the corresponding inferior paracentral region). The boxes with solid lines indicate the peripheral loss regions: the nasal step and temporal wedge regions in the superior hemifield and the Bjerrum region in the inferior hemifield. There is overlap between the Bjerrum region and the second row of the paracentral region. This was because the superior Bjerrum region evaluated had to be restricted as during VF review, we omitted the superior-most row of points in the upper visual field, which could be affected by ptosis; for symmetry, we applied the same overlap in the inferior hemifield. For a case to be defined as having peripheral loss, VF loss in the superior or inferior nasal step, temporal wedge, or Bjerrum regions had to be present with no loss in the paracentral regions. For a case to be defined as having early paracentral loss, VF loss in the superior or inferior paracentral zones had to be present without any peripheral VF loss or with peripheral VF loss, except for temporal wedge VF loss, in the same hemifield as the paracentral VF loss (those with advanced loss not meeting these criteria were censored at diagnosis). Here, the PD plot shows superior paracentral VF loss only (thick dashed lines).