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Editors Selection IGR 9-2
Risk Factors: The potential role of blood pressure in VF progression - I
Comment by Alon Harris on:
Risk factors for primary open angle glaucoma (POAG) include elevated intraocular pressure (IOP), genetics, myopia, high and low blood pressure (BP) and retinal/optic nerve head (ONH) vascular impairments.1-2 Diurnal fluctuations and variability in physiological biomarkers have also been associated with POAG. Specifically, non-physiologic nocturnal BP dipping and wider circadian fluctuations in ocular perfusion pressures (OPP-calculated from IOP and BP) have been identified in POAG patients.3 Higher daytime baseline standard deviation (SD) in mean arterial pressure (MAP) and OPP have also previously been found to be predictors of visual field (VF) progression in patients with normal tension glaucoma.4
In the current study Pham et al. present novel data on the long-term variability of BP and how it is associated with VF progression in patients with suspected or confirmed glaucoma. The researchers found higher mean BP and higher SD of BP were associated with faster rates of VF progression. Specifically, they identified how the variability of BP readings over 8 years was associated with steeper VF MD slopes. Their work indicates faster disease progression associated with both MAP and diastolic arterial pressure (DAP), especially when combined with higher mean BP and IOP. Perhaps more interesting, both low MAP and DAP, when combined with low mean IOP and increased SD, also resulted in steeper MD slopes.
Both low MAP and DAP, when combined with low mean IOP and increased SD, also resulted in steeper MD slopes
Strengths of the current work include the uniformity of dual protocols used in the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study and the sample size of 1,674 eyes from 985 patients. Limitations include absence of blood flow assessments (i.e. optical coherence tomography angiography-OCTA), not accounting for systemic and ocular medication use, and not assessing diurnal fluctuations or structural assessments including the retinal nerve fiber layer.
Pham and coworkers should be congratulated for this important contribution on BP variability and its relationship to functional POAG progression. The combination of machine learning (ML) and mathematical modeling has previously demonstrated how subjects with both low BP and high IOP are more susceptible to POAG progression.5-6 The Singapore Epidemiology of Eye Diseases study (SEED) of 19,587 eyes found that low systolic BP coupled with high IOP may result in reduced perfusion to the ONH in ocular hypertensive eyes (OR=3.90).7 The highly interesting results presented here by Pham and coworkers are therefore in strong agreement with the large and growing body of evidence linking BP, and potentially its variability, to the onset and progression of POAG. Future work may consider including direct vascular assessments using OCTA or other advanced imagery to reveal the metabolic impact of BP and IOP combinations and their variability on retinal and ONH tissues.
References
- Harris A, Guidoboni G, Siesky B, Mathew S, Verticchio Vercellin AC, Rowe L, Arciero J. Ocular blood flow as a clinical observation: Value, limitations and data analysis. Prog Retin Eye Res. 2020 Jan 24:100841.
- Weinreb RN, Harris, A. World Glaucoma Association Consensus Series – 6. Ocular blood flow in glaucoma. Kugler Publications, Amsterdam, the Netherlands. 2009.
- Werne A, Harris A, Moore D, BenZion I, Siesky B. The circadian variations in systemic blood pressure, ocular perfusion pressure, and ocular blood flow: risk factors for glaucoma? Surv Ophthalmol. 2008 Nov-Dec;53(6):559-67. doi: 10.1016/j. survophthal.2008.08.021. PMID: 19026319.
- Lee J, Choi J, Jeong D, Kim S, Kook MS. Relationship between day-time variability of blood pressure or ocular perfusion pressure and glaucomatous visual field progression. Am J Ophthalmol. 2015 Sep;160(3):522-537.e1. doi: 10.1016/j. ajo.2015.05.034. Epub 2015 Jun 4. PMID: 26052089.
- Rai, R., Guidoboni, G., Wikle, C. K., Topouzis, F., Siesky, B., Verticchio Vercellin, A., Antman, G., Harris, A. Retinal Venous Vulnerability in Primary Open Angle Glaucoma: The Combined Effects of Intraocular Pressure and Blood Pressure with Application to the Thessaloniki Eye Study. La Matematica 4, 66–83 (2025). https://doi.org/10.1007/ s44007-024-00144-8.
- Kellner, R., Harris, A., Ciulla, L., Rai R., Siesky, B., Topouzis, F. Verticchio Vercellin, A., Antman, G., Keller, J., Zou, D., Wikle, C., Guidoboni. G. Blood pressure and glaucoma: can physiology enhanced artificial intelligence solve the enigma? Glaucoma Research and Clinical Advances: 2022 to 2024, pp. 1-14 Edited by J.R. Samples and W.D. Stamer (2024) Kugler Publications, Amsterdam, The Netherlands.
- Tham YC, Lim SH, Gupta P, Aung T, Wong TY, Cheng CY. Inter-relationship between ocular perfusion pressure, blood pressure, intraocular pressure profiles and primary open-angle glaucoma: the Singapore Epidemiology of Eye Diseases study. Br J Ophthalmol. 2018 Oct;102(10):1402-1406. doi: 10.1136/bjophthalmol-2017-311359. Epub 2018 Jan 13. PMID: 29331952.
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