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Progression / Prognostic Factors: Blood pressure affects progression differently by optic disc phenotype

Comment by Yongjin Na & Michael Kook on:

126828 Effect of Blood Pressure on Rates of Progression in Focal Ischemic vs. Generalized Cup Enlargement Glaucoma Phenotypes, Guerreiro-Filho M; Jammal AA; Muralidhar R et al., Ophthalmology. Glaucoma, 2025; 8: 293-301

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Classifying optic disc phenotypes (ODPs) is clinically relevant because they are associated with different clinical profiles. For example, focal ischemic (FI) phenotypes are linked to nocturnal hypotension, Raynaud’s phenomenon, and vascular dysregulation, whereas generalized enlargement (GE) phenotypes are more often associated with elevated baseline intraocular pressure (IOP) [1-3]. In the present study, the authors report that although IOP during follow-up similarly influenced glaucoma progression in both FI and GE phenotypes, FI eyes demonstrated greater vulnerability to lower diastolic blood pressure (BP) compared with GE eyes. These findings suggest that systemic vascular factors, such as low BP, may need to be considered in addition to IOP when managing glaucoma according to ODP subtype—underscoring the importance of personalized treatment strategies.

Using linear mixed models, the investigators found that each 10 mmHg reduction in mean arterial pressure (MAP), systolic arterial pressure (SAP), and diastolic arterial pressure (DAP) was associated with faster retinal nerve fiber layer (RNFL) thinning in FI eyes (–0.397 µm/year, –0.211 µm/year, and –0.471 µm/year, respectively; all P<0.05). By contrast, BP parameters were not significantly associated with RNFL loss in GE eyes. Importantly, in multivariable models incorporating interaction terms, the interaction between DAP and phenotype reached statistical significance (P=0.019), highlighting the particular influence of low DAP on RNFL progression in FI eyes.

A strength of this study lies in the use of structural measures—global RNFL thickness—to quantify glaucoma progression, providing an objective estimate of retinal ganglion cell loss. Another strength is the repeated measurement of BP on the same day as IOP, with mean SAP, DAP, and MAP values over the study period serving as surrogate markers of systemic BP. However, global RNFL thickness may mask localized RNFL changes that differ between FI and GE eyes, particularly in this early-stage cohort (baseline MD: –3.86 and –2.13 dB, respectively). Moreover, systemic BP is dynamic, exhibiting circadian variation that has been linked to glaucoma progression. While multiple BP readings were collected during follow-up, office-hour measurements may not fully capture individual BP behavior, potentially influencing the observed associations. Additional limitations include the relatively small sample size in each group and potential selection bias.

Despite these limitations, the study highlights the vulnerability of FI phenotypes to low systemic BP and supports a personalized management approach. Future integration of advanced imaging, artificial intelligence–based ODP classification, and large-scale BP behavior data may enhance risk stratification and individualized treatment in glaucoma.

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