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: 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.