Progression of Retinopathy Secondary to Maternally Inherited Diabetes and Deafness – Evaluation of Predicting Parameters

Abstract

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Retinal Manifestations of Mitochondrial Oxidative Phosphorylation Disorders

“…A recently published autofluorescence study of MIDD observed that retinal degeneration developed at eccentricities of 10 to 20 degrees with foveal sparing, unlike in other macular dystrophies, which typically affect the center. 19 This feature was also observed in our patients, although the fovea was affected in both eyes of P1 and the right eye of P3. We hypothesize that this parafoveal atrophy and foveal sparing may in part be due to a higher heteroplasmy levels of the mutation specifically in the cells at eccentricities of 10 degrees to 20 degrees as compared to the rest of the retina, or due to the varied expression of antioxidant enzymes described in proteomic analyses of these anatomic regions in the RPE and retina.…”

“…In recent studies of MIDD, Müller et al have hypothesized that RPE atrophy may precede photoreceptor death in MIDD, and by extension mitochondrial diseases, based upon a combination of longitudinal SW-AF and SD-OCT analysis, which revealed a delay between RPE atrophy and subsequent visual acuity loss and retinal thinning as seen on SD-OCT. 19,20 In our cohort, we observed a number of additional features that support this hypothesis in both MIDD and KSS.…”

“…Specifically, they found that there was a delay between retinal thinning and visual acuity loss as compared to RPE loss and hypertransmission of OCT signal into the choroid. 19,20 In this study, we expand upon and compare the phenotypic characteristics of a cohort of patients diagnosed with MIDD and KSS and discuss features that may support the hypothesis that initial mitochondrial dysfunction within the RPE is the primary site of disease pathogenesis.…”

“…This spatial correlation of newly developing ORTs occurring at the boundary of preserved and atrophic RPE as seen on SW-AF has been previously described by Goldberg et al who suggest these areas may retain residual function, as well as by Müller et al in their recent study. 19,33 In an area of intact retina located between two separate islands of atrophy, the presence of a developing ORT was observed, which may predict impending RPE atrophy at this location (see Fig. 4A, yellow arrow).…”

“…Within our cohort, the mean age of visual symptom onset was significantly higher in patients with MIDD (44.6 ± 11.6 years) as compared to patients with KSS (23.0 ± 10.0 years), which was consistent with prior reports in the literature. [19][20][21][22] Despite the later onset of disease, the retinal phenotype seen in MIDD was a pattern macular dystrophy with frank RPE atrophy, which was notably more severe than the pigmentary changes and RPE mottling observed in KSS. SD-OCT images in patients with MIDD similarly revealed significant retinal and RPE atrophy with ORTs, whereas those in patients with KSS were unremarkable with the exception of P6.…”