Mitochondrial Dysfunction in Primary Open-angle Glaucoma Characterized by Flavoprotein Fluorescence at the Optic Disc Rim

Abstract

Purpose : Recent studies have implicated mitochondrial dysfunction in the pathophysiology of glaucoma, with in vivo characterization at the macula by Geyman et al. Evaluation of these mitochondrial alterations has been enabled measurement of flavoprotein fluorescence (FPF) through a non-invasive imaging platform. The current study is the first to evaluate FPF at the optic disc rim in primary open-angle glaucoma (POAG) patients compared to healthy controls.

Methods : 50 eyes of 30 POAG patents and 36 eyes of 20 healthy controls were imaged using the OcuMet Beacon (OcuSciences, Ann Arbor, MI; Investigational Device). Infrared and FPF measurements were obtained at the optic nerve head (ONH). Built-in software algorithms identified the optic disc margins on the infrared image and demarcated an elliptical annulus around the ONH rim. FPF was subsequently measured within the annulus boundaries. Averaged FPF of the entire area within the annulus and within anatomical sectors (temporal, superior, nasal, and inferior) were determined for each subject. Distinctions in FPF between POAG and control eyes were evaluated through mixed-effects logistic regression, adjusted for age and interocular pressure. Correlation between FPF and clinical characteristics for glaucoma were also characterized using linear mixed-effects models.

Results : The mean±SD of global FPF was significantly higher in POAG eyes compared to control eyes (46.4±27.9 vs. 28.0±11.7, P<0.001). Differences in FPF between POAG and controls eyes were also present for temporal (P=0.001), superior (P<0.001), nasal (P=0.002), and inferior (P=0.001) sectors. FPF exhibited significant correlation to Humphrey 24-2 visual field mean deviation (P=0.001). Significant correlation was also present between global FPF and global circumpapillary retinal nerve fiber thickness (P< 0.001) and at the superior (P=0.02), inferior (P=0.02), and nasal (P=0.003) quadrants.

Conclusions : Measurement of FPF suggests increased mitochondrial dysfunction at the optic disc rim in POAG eyes. FPF may prove useful for evaluation of glaucomatous damage and may permit further exploration of pathophysiology. Future studies on stage-stratified POAG eyes will aim to assess the potential roles for FPF assessment in the detection of early glaucomatous pathology.

This is a 2021 ARVO Annual Meeting abstract.