Retinal flavoprotein fluorescence could be new biomarker of AMD stage, progression

Mitochondria, often referred to as the powerhouses of the cell, help turn the energy we ingest from food into energy the cell can use. Oxidative stress-induced mitochondrial dysfunction is a well-known part of the pathophysiology (disease caused functional changes) of AMD. Therefore, a marker of mitochondrial dysfunction could serve as an indicator of AMD stages, helping to detect early disease and offering insights on how and when to treat patients. 

Flavoproteins serve an essential role in normal mitochondrial function. When oxidized, under blue light stimulation they glow with a green autofluorescence signal that could potentially be used as a biomarker of mitochondrial dysfunction. Until recently, mitochondria were not visible and couldn’t be counted in live tissue but advances in retinal imaging have now made this possible, according to Rishi P. Singh, MD, principal investigator of the study.  

Singh and team used an investigative device (OcuMet Beacon, OcuSciences) to measure flavoprotein florescence (FPF) intensity and heterogeneity (differences) of 228 eyes with various stages of AMD and 228 control eyes. A statistical analysis showed that intermediate AMD, neovascular (wet) AMD and geographic atrophy (GA) were correlated with significant increase of FPF intensity and heterogeneity. Both values were also significantly correlated with decreased best corrected visual acuity. Variables that predict AMD progression, such as age, sex and smoking, and increased FPF intensity were also associated.   

Long-term trials are needed to evaluate the predictive role of FPF imaging over time. However, the findings of this study suggest that FPF may be useful in a clinical setting and has the potential to provide “a better understanding of the underlying pathophysiology of AMD, particularly the role of mitochondrial dysfunction in AMD and its progression,” the authors said.  “Our recent studies have demonstrated correlations of increased FPF with diabetic retinopathy severity as well as AMD. In addition, our research has identified changes following anti-VEGF use, suggesting that FPF could be also a potential biomarker for treatment response. Future studies will expand upon this direct correlation and how it might predict visual acuity improvements,” Singh said. 

Disclosure: One of the authors is an employee of OcuSciences, the maker of the investigative device. 

Healio Oph, February 23, 2023; see source article, DOI:10.3928/23258160-20221214-03