Background: Nocturnal hypoperfusion has been documented as the main vascular systemic risk factor associated with primary open-angle glaucoma (POAG). However, beyond the level, exaggerated mean arterial pressure (MAP) variability over 24-h could also be associated with glaucoma damage. We aimed to investigate the association of POAG damage with 24-h blood pressure (BP) dysregulations.

Methods: We conducted cross-sectional and longitudinal studies that included 93 participants from the general population (mean age 61.9y, 87.1% women) and patients from a glaucoma unit who underwent 24-h ambulatory BP monitoring (mean age 64.0y, 53% women, median follow-up of 9y). In the cross-sectional study, the primary outcome was the presence of POAG. In the longitudinal study, the outcomes included (i) functional (visual field defects expressed as mean deviation [MD]) and (ii) structural (optic disc cupping obtained from cup-to-disc ratio) glaucoma damage. BP dysregulations were separately investigated for 24-h, diurnal, and nocturnal periods as (i) MAP variability independent of the mean (VIMmap), (ii) extreme sporadic drops in MAP, and (iii) the night-to-day ratio. Statistics included multivariable linear, logistic, and mixed regression models and log-likelihood ratio test.

Results: In the cross-sectional analyses, the risk of glaucoma increased with (i) extreme nocturnal BP dipping (P≤0.045), (ii) high 24-h VIMmap (odds ratios [OR], 1.93; 95% confidence interval [CI], 1.10-3.41 per 2 mmHg increase in VIMmap), and (iii) drops rather than increases in the MAP over 24-h (OR and 95% CI ranged between 2.25 to 3.39 and 1.23 to 8.46, respectively). In the longitudinal study, functional progression of glaucoma damage was associated with VIMmap (-2.57 dB change in MD per every 3 mmHg increase in VIMmap; P<0.001) and diurnal MAP dips (changes in the MD ranged from -2.56 to -3.19 dB; P<0.001). Every 5 mmHg decrease in the nocturnal MAP level was associated with -1.14 dB changes in MD (95% CI, -1.90 to -0.40) and 0.01 larger optic disc cupping (95% CI, 0.01 to 0.02,). Lower night-to-day ratio was also related to both outcomes (P≤0.012). Functional glaucoma damage worsened in the presence of reduced ocular perfusion pressure (MD changes ranged from -2.51 to -2.00 dB), and if nocturnal hypotension was combined with high variability or extreme dips in the diurnal MAP (P≤0.022).

Conclusions: Glaucoma damage in POAG associates with high variability and extreme dips in the diurnal MAP, and nocturnal hypotension. Ambulatory blood pressure monitoring in combination with intraocular pressure measurements might offer an opportunity to improve the risk stratification of open-angle glaucoma.