Functional imaging of mitochondria using flavoprotein fluorescence and its correlation with intraocular pressure in treated glaucoma patients

Abstract

Purpose : Increased intraocular pressure (IOP) is believed to induce oxidative stress and lower antioxidant defenses in the optic nerve, leading to retinal ganglion cell death. A noninvasive retinal metabolic imaging device measures flavoprotein fluorescence (FPF), a potential biomarker for mitochondrial dysfunction and early apoptosis due to oxidants and other stimuli. We evaluated the relationship between FPF and IOP to investigate the functionality of the device and the pathophysiology underpinning glaucoma.

Methods : 52 eyes from 52 patients with glaucoma or suspect glaucoma were imaged. FPF scores were obtained at the optic nerve head (ONH) and macula using OcuMet Beacon (OcuSciences Inc., Ann Arbor, MI). Optical coherence tomography obtained the retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC) thicknesses. The association between IOP and FPF, adjusting for age, sex, and RNFL, was evaluated by linear regression.

Results : Glaucoma eyes (n=34) on average had lower IOP (13.4 vs. 16.4mmHg), thinner RNFL (72 vs. 90µm), and thinner macular GCC (66 vs. 79µm) compared to suspects. All glaucoma eyes were treated and most were on IOP-lowering drugs. Among these, higher IOP correlated with a higher FPF score at the ONH but was not statistically significant (p=0.23). For suspect eyes, the opposite relationship was observed between IOP and FPF (p=0.03), but this was not significant when RNFL thickness was taken into account by using the ratio of FPF to RNFL (FPF/RNFL). Two glaucoma eyes were outliers with low IOP (7 and 10mmHg) and high FPF/RNFL. In multivariable analysis, older age, male sex, and greater RNFL thickness were associated with higher FPF scores.

Conclusions : IOP may not be the sole contributor for mitochondrial dysfunction in treated glaucoma patients. Since the majority of glaucoma patients are stable on IOP-lowering drugs, this result may reflect that little RGC stress and apoptosis occur in controlled disease. These drugs are also thought to exert additional antioxidant activity. The two outliers had more advanced glaucoma (RNFL: 49 and 55µm) and may represent greater mitochondrial stress and progressing disease despite adequate IOP control. Longitudinal studies with a wider disease severity spectrum are needed to better establish the relationship between IOP and FPF.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

 

Linear regression models of potential predictors of FPF score.