Mitochondrial Dysfunction in Primary Open-Angle Glaucoma Characterized by Flavoprotein Fluorescence at the Optic Nerve Head

Abstract

Purpose: To investigate the presence of flavoprotein fluorescence (FPF) at the optic nerve head (ONH) rim as a marker of mitochondrial dysfunction in primary open-angle glaucoma (POAG) and control eyes.

Design: Retrospective cross-sectional study of patients recruited from the New York Eye and Ear Infirmary of Mount Sinai.

Participants: A total of 86 eyes (50 eyes of 30 patients with POAG and 36 eyes of 20 control participants) were enrolled. The presence of POAG was defined by circumpapillary retinal nerve fiber layer thickness (cpRNFLT) of less than the bottom fifth percentile of the normative database, glaucomatous ONH changes, and visual field defects on 24-2 tests.

Methods: Primary open-angle glaucoma and control eyes were imaged using the OcuMet Beacon. A 23° × 23° infrared scan was obtained, and an FPF scan was performed within a capture field spanning 13° in diameter. The ONH margins on the infrared image were identified by software algorithms. Then, FPF was measured within an elliptical annulus around the ONH rim, with the inner and outer boundaries corresponding to 0.5 to 1.1 times the ONH rim size.

Main outcomes measures: Flavoprotein fluorescence at the OHN rim in POAG and control eyes.

Results: Differences in FPF between POAG and control eyes were characterized through mixed-effects logistic regression, adjusted for age and interocular pressure. Flavoprotein fluorescence was significantly higher in POAG versus control eyes, with a mean ± SD of 46.4 ± 27.9 versus 28.0 ± 11.7 (P < 0.001), respectively. Among POAG eyes, FPF showed correlation to visual field mean deviation (P < 0.001), visual field pattern standard deviation (P = 0.003), and cpRNFLT (P = 0.001) on linear mixed-effects models.

Conclusions: Higher FPF in POAG versus control eyes suggests the presence of mitochondrial dysfunction at the ONH rim in eyes with glaucomatous damage. The degree of FPF corresponds to disease severity, as measured by visual field and nerve fiber layer thickness metrics. Thus, FPF may represent a metabolic indicator of disease status that reveals the extent of injury in glaucoma.

Keywords: Flavoprotein; Glaucoma; Metabolic; Mitochondria.