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Abstract

Background: Glaucoma is a multifactorial, progressive optic neuropathy, for which both mechanical and vascular mechanisms of pathogenesis have been proposed. Optical coherence tomography angiography (OCTA) enables noninvasive visualization of the choroidal and retinal vasculature and may be used to quantify vascular changes associated with glaucoma. Systemic risk factors, including variations in blood pressure (BP), whether low or elevated, have been associated with the vascular pathogenesis of glaucoma. This systematic review aims to synthesize the current evidence on the relationship between systemic vascular dysregulation and OCTA-derived retinal vascular markers in glaucomatous eyes.

Methods: Following PRISMA guidelines, we conducted a systematic search of the literature using the PubMed and Web of Science databases. Inclusion and exclusion criteria included peer-reviewed original articles that examined markers of systemic and retinal vasculature dysregulation in relation to glaucoma in human subjects using retinal imaging techniques such as OCTA. The search yielded 825 records. After removing 294 duplicates and screening titles and abstracts, we identified 20 articles that met the inclusion and exclusion criteria. For each article, we extracted sample size, subgroup designation, subject age and sex distributions, as well as significant outcomes, which were synthesized qualitatively.

Results: Across the 20 selected studies, cohort sizes ranged from 22 to 267 participants (median = 79.5), and most subjects were in their 50s-60s. Although study methodologies varied, findings consistently demonstrated an association between systemic vascular dysregulation and retinal microvascular indices of glaucomatous progression. Lower diastolic BP correlated with parapapillary deep-layer microvasculature dropout. Conversely, elevated BP was associated with decreased macular vessel density (VD) in glaucomatous eyes exhibiting disc hemorrhage. Greater arterial stiffness, quantified by higher pulse wave velocity, was associated with lower macular VD. Across 5 studies, diurnal fluctuations in retinal VD measured using OCTA were consistently larger in glaucomatous eyes than in healthy controls, paralleling concurrent systemic BP and ocular perfusion pressure fluctuations. Pronounced nocturnal dips in mean arterial pressure (MAP) were also associated with reduced parapapillary choroidal VD. Peripherally, nailfold capillary abnormalities were associated with decreased optic nerve head and peripapillary VD and blood flow on OCTA, and together they were more common in glaucomatous subjects than in controls. Finally, one study demonstrated that a decrease in the peripapillary microcirculation seen on OCTA was more closely correlated with intraocular pressure elevation than with the presence of systemic vascular risk factors, specifically hypertension, whereas another study found that correction for baseline MAP is necessary when determining retinal VD loss.

Conclusions: Systemic vascular dysregulation is associated with retinal microvasculature changes in glaucoma. Studies aimed at establishing causality and clarifying the clinical applications of these markers are needed. Further research is necessary to determine whether therapies targeting systemic hemodynamics may prove useful as adjuncts to intraocular pressure-lowering treatments.

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Poster

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Systemic Vascular Dysregulation and Retinal Microvascular Alterations in Glaucoma

Background: Glaucoma is a multifactorial, progressive optic neuropathy, for which both mechanical and vascular mechanisms of pathogenesis have been proposed. Optical coherence tomography angiography (OCTA) enables noninvasive visualization of the choroidal and retinal vasculature and may be used to quantify vascular changes associated with glaucoma. Systemic risk factors, including variations in blood pressure (BP), whether low or elevated, have been associated with the vascular pathogenesis of glaucoma. This systematic review aims to synthesize the current evidence on the relationship between systemic vascular dysregulation and OCTA-derived retinal vascular markers in glaucomatous eyes.

Methods: Following PRISMA guidelines, we conducted a systematic search of the literature using the PubMed and Web of Science databases. Inclusion and exclusion criteria included peer-reviewed original articles that examined markers of systemic and retinal vasculature dysregulation in relation to glaucoma in human subjects using retinal imaging techniques such as OCTA. The search yielded 825 records. After removing 294 duplicates and screening titles and abstracts, we identified 20 articles that met the inclusion and exclusion criteria. For each article, we extracted sample size, subgroup designation, subject age and sex distributions, as well as significant outcomes, which were synthesized qualitatively.

Results: Across the 20 selected studies, cohort sizes ranged from 22 to 267 participants (median = 79.5), and most subjects were in their 50s-60s. Although study methodologies varied, findings consistently demonstrated an association between systemic vascular dysregulation and retinal microvascular indices of glaucomatous progression. Lower diastolic BP correlated with parapapillary deep-layer microvasculature dropout. Conversely, elevated BP was associated with decreased macular vessel density (VD) in glaucomatous eyes exhibiting disc hemorrhage. Greater arterial stiffness, quantified by higher pulse wave velocity, was associated with lower macular VD. Across 5 studies, diurnal fluctuations in retinal VD measured using OCTA were consistently larger in glaucomatous eyes than in healthy controls, paralleling concurrent systemic BP and ocular perfusion pressure fluctuations. Pronounced nocturnal dips in mean arterial pressure (MAP) were also associated with reduced parapapillary choroidal VD. Peripherally, nailfold capillary abnormalities were associated with decreased optic nerve head and peripapillary VD and blood flow on OCTA, and together they were more common in glaucomatous subjects than in controls. Finally, one study demonstrated that a decrease in the peripapillary microcirculation seen on OCTA was more closely correlated with intraocular pressure elevation than with the presence of systemic vascular risk factors, specifically hypertension, whereas another study found that correction for baseline MAP is necessary when determining retinal VD loss.

Conclusions: Systemic vascular dysregulation is associated with retinal microvasculature changes in glaucoma. Studies aimed at establishing causality and clarifying the clinical applications of these markers are needed. Further research is necessary to determine whether therapies targeting systemic hemodynamics may prove useful as adjuncts to intraocular pressure-lowering treatments.

 

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