Cold Extremities and Underweight as a Combined Risk Profile for Open-Angle Glaucoma: A Population-Based...

Background/Objectives: Glaucoma is one of the leading causes of irreversible blindness worldwide. Open-angle glaucoma (OAG) predominates in East Asian populations, with normal-tension glaucoma accounting for the majority of cases. Although intraocular pressure remains the most established risk factor, non-pressure-dependent mechanisms, including ocular vascular dysregulation, warrant further investigation. Cold extremities, a hallmark of Flammer syndrome reflecting primary vascular dysregulation, and underweight (body mass index [BMI] < 18.5 kg/m²) are each independently associated with OAG; however, their combined effect has not been examined at the population level. Materials and Methods: Using nationally representative data from the Korea National Health and Nutrition Examination Survey 2008-2012 (n = 8135; controls 7418, OAG 717), participants aged ≥ 50 years with measured intraocular pressure within the normal range (5-21 mmHg) at the time of examination were classified into four groups: non-underweight without cold extremities (N-N, reference), cold extremities only (CEO), underweight only (UWO), and underweight with cold extremities (UW+CE). Complex sample logistic regression was adjusted for sex, age, diabetes mellitus, mean arterial pressure, intraocular pressure, and spherical equivalent. Results: UW+CE was associated with significantly higher odds of OAG than N-N (adjusted odds ratio [OR] = 2.10, 95% confidence interval: 1.14-3.88, p = 0.018), whereas neither CEO (OR = 1.10, p = 0.431) nor UWO (OR = 1.54, p = 0.170) was significantly associated individually. This association with UW+CE remained robust across alternative BMI thresholds and after further adjustment for socioeconomic, lifestyle, and cardiometabolic variables. Conclusions: Co-occurring cold extremities and underweight status were associated with a combined hemodynamic risk profile for OAG, suggesting their potential utility as clinically accessible noninvasive markers for the early identification of highly vulnerable individuals and informing proactive glaucoma screening strategies.