Nicotinamide Prevents Retinal Vascular Dropout in a Rat Model of Ocular Hypertension and Supports Ocular Blood Supply in Glaucoma Patients

Abstract

PURPOSE: To investigate whether nicotinamide (NAM) modulates retinal vasculature in glaucoma. METHODS: This was a prospective controlled clinical trial investigating animal and human histopathology. Participants included normotensive and ocular hypertensive rats, postmortem human ocular tissue, glaucoma patients (n = 90), and healthy controls (n = 30). The study utilized histopathology, computer-assisted retinal vasculature analysis, optical coherence tomography angiography (OCTA), and NAM treatment. The main outcome measures included retinal vascular parameters in rats as assessed by AngioTool; retinal vasculature integrity in rats and humans as assessed by histopathology, antibody-staining, and ImageJ-based measurements; and retinal perfusion density (PD) and flux index in humans as assessed by OCTA. RESULTS: A number of vessel parameters were altered in ocular hypertension/glaucoma compared to healthy controls. NAM treatment improved the retinal vasculature in ocular hypertensive rats, with an increase in mean vessel area, percentage area covered by vessels, total vessel length, total junctions, and junction density as assessed by AngioTool (all P < 0.05); vessel wall integrity as assessed by VE-cadherin antibody staining was also improved (P < 0.01). In humans, as assessed by OCTA, increases in PD in the optic nerve head and macula complete image (0.7%, P = 0.04 and 1.0%, P = 0.002, respectively) in healthy controls, and an increase in the temporal quadrant of the macula (0.7%, P = 0.02) in glaucoma patients was seen after NAM treatment. CONCLUSIONS: NAM can prevent retinal vascular damage in an animal model of glaucoma. After NAM treatment, glaucoma patients and healthy controls demonstrated a small increase in retinal vessel parameters as assessed by OCTA.