Vascular dysregulation in glaucoma: retinal vasoconstriction and normal neurovascular coupling in altitudinal visual field defects

Abstract

Purpose Vision loss in glaucoma is not only associated with elevated intraocular pressure and neurodegeneration, but vascular dysregulation (VD) is a major factor. To optimize therapy, an improved understanding of concepts of predictive, preventive, and personalized medicine (3PM) is needed which is based on a more detailed understanding of VD pathology. Specifically, to learn if the root cause of glaucomatous vision loss is of neuronal (degeneration) or vascular origin, we now studied neurovascular coupling (NVC) and vessel morphology and their relationship to vision loss in glaucoma. Methods In patients with primary open angle glaucoma (POAG) (n = 30) and healthy controls (n = 22), NVC was studied using dynamic vessel analyzer to quantify retinal vessel diameter before, during, and after flicker light stimulation to evaluate the dilation response following neuronal activation. Vessel features and dilation were then related to branch level and visual field impairment. Results Retinal arterial and venous vessels had significantly smaller diameters in patients with POAG in comparison to controls. However, both arterial and venous dilation reached normal values during neuronal activation despite their smaller diameters. This was largely independent of visual field depth and varied among patients. Conclusions Because dilation/constriction is normal, VD in POAG can be explained by chronic vasoconstriction which limits energy supply to retinal (and brain) neurons with subsequent hypo-metabolism (“silent” neurons) or neuronal cell death. We propose that the root cause of POAG is primarily of vascular and not neuronal origin. This understanding can help to better personalize POAG therapy of not only targeting eye pressure but also vasoconstriction to prevent low vision, slowing its progression and supporting recovery and restoration. Trial registration ClinicalTrials.gov, # NCT04037384 on July 3, 2019.

Comparison of the Choroid in Primary Open Angle and Angle Closure Glaucoma Using Optical Coherence Tomography

“…30 Another study revealed that peripapillary arteriolar and venular tortuosity, arteriolar branching angle, circumpapillary vessel density, and circumpapillary fractal dimension were reduced in eyes with POAG. 31 A recent study by Zhou and Sabel 32 showed a significant decline in the diameter of retinal arterial and venous vessels in patients with POAG compared with healthy individuals using a dynamic vessel analyzer. They proposed that vascular dysregulation in POAG may be attributable to chronic vasoconstriction, which hinders the energy supply to retinal neurons and eventually results in neuronal cell death.…”

Analysis of retinal arteriolar and venular parameters in primary open angle glaucoma

“…Another finding of this study is that there was no difference in the venular parameters between POAG patients and the normal group. However, the diameter of the retinal arteriole decreased significantly, indicating that the pressure in the retinal vessel and outflow resistance increased [36] . This may reflect the relationship between glaucoma and the increased frequency of retinal vein occlusion.…”

Glaukompatient mit Verdacht auf Flammer-Syndrom: diagnostische Schritte und therapeutische Konsequenzen

“…Eine neue Perspektive gelang mit der Erkenntnis, dass beim Glaukom nicht nur oder sogar weniger die Arteriosklerose und ihre Risikofaktoren entscheidend sind, sondern eine vaskuläre Dysregulation, und zwar vor allem die primäre Form der vaskulären Dysregulation (PVD) 2 . Diese Hypothese wurde zuerst von J. Flammer und Mitarbeitern formuliert 17 und anschließend von mehreren Gruppen bestätigt 18 , 19 , 20 , 21 , 22 .…”