Correlation of Optic Nerve Head and Peripapillary Microvasculature With Nailfold Capillary Measurements in Patients With Primary Open Angle Glaucoma

Abstract

Background: Glaucoma, a progressive disease of the optic nerve in the eye, is the leading cause of irreversible blindness worldwide. A better understanding of the mechanisms involved in the onset and progression of glaucoma is essential for the development of improved diagnostic and therapeutic options for this condition. Glaucoma is thought to result from mechanical, ischemic, and other types of insult to the retinal ganglion cells and their axons, but the pathophysiology of ischemia in glaucoma remains unclear. Optic nerve head (ONH) and peripapillary retina microvasculature pathology as well as abnormalities of systemic microcirculation, specifically the nailfold capillaries, have independently been found in patients with glaucoma compared to control subjects. These findings suggest that measurements of nailfold capillary vasculature may correlate with those of the microvasculature in the eye in patients with primary open-angle glaucoma (POAG). Methods: POAG patients and control subjects underwent swept-source optical coherence tomography angiography (SS-OCTA) and nailfold video capillaroscopy of the fingers. SS-OCTA was used to measure microvascular vessel density and Integrated OCTA by ratio analysis Signal (IOS), a surrogate marker for blood flow, of different layers of the ONH and peripapillary region of the eye with worse functional loss indicated by Humphrey Visual Field mean deviation (HVF MD) in POAG patients and of one randomly selected eye in control subjects. Nailfold capillary density and blood flow were also measured. SS-OCTA parameters (vessel density and IOS) from the eye were plotted against nailfold capillary density and blood flow respectively, and Pearson’s correlation (r) was calculated. Results: 22 POAG patients (HVF MD: -3.5 ± 2.8 dB) and 12 control subjects were included. POAG patients were younger than control subjects (64 ± 10 years vs 70 ± 7 years, p = 0.03) but similar in gender and ethnicity (42% male, 88% Caucasian overall, p > 0.72). Superficial ONH vessel density and flow (IOS) were not significantly different in POAG vs control subjects (p > 0.20). Deep ONH vessel density and flow and peripapillary vessel density and flow were lower in POAG patients (39.1 ± 3.5%, 37.8 ± 5.3%, 37.9 ± 2.6%, 44.1 ± 3.1%, respectively) than control subjects (43.8 ± 5.7%, p = 0.02; 46.0 ± 7.8%, p = 0.005; 43.4 ± 7.6%, p = 0.03; 46.8 ± 3.9%, p = 0.05, respectively). Nailfold capillary density and blood flow were also lower in POAG patients compared to control subjects (8.8 ± 1.0 capillaries/mm vs 9.8 ± 0.9 capillaries/mm, p = 0.009; 19.9 ± 9.4 pL/s vs 33.7 ± 9.8 pL/s, p = 0.0007). There were significant correlations between deep ONH flow and nailfold capillary blood flow (r = 0.43, p = 0.01), peripapillary and nailfold capillary density (r = 0.43, p = 0.01), and peripapillary flow and nailfold capillary blood flow (r = 0.50, p = 0.003). Subgroup analysis was performed to assess the correlation between nailfold capillary and ophthalmic microvasculature measurements in POAG patients (n = 22) and control subjects (n = 12) separately, with significant correlation between nailfold capillary density and deep ONH vessel density in control subjects (r = -0.80, p = 0.002) but no other significant correlations. Additional subgroup analysis of POAG patients divided into high-tension and normal-tension glaucoma groups based on maximum intraocular pressure demonstrated statistically significant correlations between nailfold capillary density and deep ONH vessel density (r = 0.61, p = 0.044) and between nailfold capillary density and flow with peripapillary vessel density and flow respectively in high-tension glaucoma patients (r = 0.60, p = 0.049; r = 0.63, p = 0.04, respectively) but no significant correlations in normal-tension glaucoma patients. Conclusions: POAG patients demonstrated decreased vessel density and flow in the deep ONH and peripapillary region of the eye compared to control subjects; POAG nailfold capillary density and blood flow were also significantly decreased. More importantly, measurements of microvasculature in the deep ONH layer and peripapillary region of the eye significantly correlated with those in terminal nailfold capillaries. These results suggest that there is an association between ophthalmic and systemic microvasculature, which may help to elucidate the pathophysiology of glaucoma as well as potentially provide new biomarkers and novel therapies for this condition in the future.