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Jessica Hsueh, Raffaele Raimondi, Grant Hom, Thais Conti, Rishi P Singh; Flavoprotein Fluorescence is a Marker of AMD Progression. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3462.
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© ARVO (1962-2015); The Authors (2016-present)
Many studies have implicated mitochondrial damage in the pathogenesis of age related macular degeneration (AMD) before structural damage to the retina occurs. Advances in imaging technology have allowed for novel ways to image flavoprotein fluorescence (FPF), which is indicative of mitochondrial dysfunction (MD). This study evaluated if differences in MD exist between the stages of AMD from early to late disease.
The study was conducted at a single institution from July to October 2018. Twenty-one non-pseudophakic eyes diagnosed with AMD were scanned with a modified EIDON confocal scanner (OcuSciences, Ann Arbor, MI) with 467 nm excitation and 535 nm emission filters to detect a fluorescence spectrum from 520 to 540nm. Raw images were analyzed with ImageJ software (NIH, Bethesda, MD) to generate FPF (average fluorescence signal intensity from gray scale units). AMD eyes were grouped into non-exudative AMD (NEAMD) (AREDS category 2, 3, or 4) and exudative AMD (EXAMD). Additionally, FPF scores were analyzed at less than one year, one to three years, and greater than three years from the time from diagnosis for NEAMD and EXAMD eyes. Paired groups were compared with two tailed t tests and all groups were compared with one way ANOVA.
The average patient age for NEAMD eyes (total n=17; AREDS cat 2 n=4, cat 3 n=11, or cat 4 n=2) and EXAMD eyes (n=4) was 71.75, 74.27, 76, and 78.5 years, respectively. Average FPF for AREDS NEAMD cat 2, 3, 4, and EXAMD were 103.7, 87.5, 83.5, and 117.4 (p= 0.8453). The EXAMD group had statistically significant (p<0.05) higher FPF compared to patients in the AREDS cat 4 group. No significant trends were found between other group pairings. In the NEAMD group, FPF at less than one year (n=3), between one to three years (n=6), and over three years (n=7) from diagnosis were 111.5, 82.6, and 99.2, respectively. Near meaningful increase in FPF over time was found between the time points one to three years and over three years from diagnosis for NEAMD eyes (p=0.06). In the EXAMD group, FPF at one to three years (n=1) and over three years (n=7) from diagnosis were 125.0 and 101.2.
Increases in fluorescence intensity from AREDS cat 4 NEAMD to EXAMD, and also over time, indicate increased FPF (a proxy for MD) correlates well with progression of AMD pathology. Mitochondrial loss during progression of NEAMD eyes may explain for downtrending FPF scores with disease severity.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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