Cardiorespiratory fitness, cardiovascular risk, and disease-related outcomes in primary open-angle glaucoma: a cross-sectional study.

OBJECTIVE: To investigate the associations of objectively measured cardiorespiratory fitness (CRF) with glaucoma-related functional, structural, and patient-reported outcomes and to compare its explanatory contribution with cumulative cardiovascular (CV) risk in patients with primary open-angle glaucoma (POAG). DESIGN: Cross-sectional baseline analysis of the multicenter HIT-GLAUCOMA trial (NCT06058598). SUBJECTS: One hundred ten patients with mild-to-moderate POAG. METHODS: CRF was assessed by symptom-limited cardiopulmonary exercise testing and expressed as peak oxygen uptake (VO2peak). Cumulative CV risk was estimated using the Systematic COronary Risk Evaluation 2 (SCORE2). Missing data were addressed using multiple imputation. Multivariable linear regression models with restricted cubic splines were used to evaluate associations. Relative explanatory contributions of CRF and SCORE2 were explored using adequacy indices derived from model R2 values. MAIN OUTCOME MEASURES: Visual field mean deviation (MD), global retinal nerve fiber layer (RNFL) thickness, Glaucoma Activity Limitation Questionnaire (GAL-9), and National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25). RESULTS: No statistically significant associations were observed between CRF or SCORE2, and glaucoma-related outcomes. Nevertheless, higher CRF showed directionally more favorable estimates for visual field performance, glaucoma activity limitation, and vision-related quality of life. Higher SCORE2 showed a directionally less favorable estimate for global RNFL thickness, whereas apparent non-linear patterns for patient-reported outcomes should be interpreted cautiously. Exploratory adequacy analyses suggested differential explanatory contributions. CRF retained 95% of the explanatory information for visual field MD compared with 60% for SCORE2, whereas SCORE2 retained more explanatory information for RNFL thickness (97% vs. 86%) and NEI-VFQ-25 scores (86% vs. 40%). Given the modest sample size and the absence of statistically significant primary associations, these adequacy findings should be considered exploratory rather than confirmatory. CONCLUSIONS: The observed directional patterns and exploratory adequacy analyses suggest that CRF and cumulative CV risk may reflect different dimensions of CV health across glaucoma-related outcomes. However, these findings are hypothesis-generating and require confirmation in larger, adequately powered longitudinal and interventional studies.