To investigate the development and progression of retinal pigment epithelial and outer retinal atrophy (RORA) secondary to maternally inherited diabetes and deafness (MIDD).

Retrospective observational case series.

Thirty-six eyes of 18 patients (age range, 22.4-71.6 years) with genetically proven MIDD and serial optical coherence tomography (OCT) images were included. As proposed reference standard to diagnose and stage atrophy, OCT images were longitudinally evaluated and analyzed for presence and precursors of RORA. RORA was defined as an area of (1) hypertransmission, (2) disruption of the retinal pigment epithelium, (3) photoreceptor degeneration, and (4) absence of other signs of a retinal pigment epithelial tear.

The majority of patients revealed areas of RORA in a circular area around the fovea of between 5° and 15° eccentricity. Over the observation time (range, 0.5-8.5 years), evidence for a consistent sequence of OCT features from earlier disease stages to the end stage of RORA could be found, starting with loss of ellipsoid zone and subretinal deposits, followed by loss of external limiting membrane and loss of retinal pigment epithelium with hypertransmission of OCT signal into the choroid, and leading to loss of the outer nuclear layer bordered by hyporeflective wedges. Outer retinal tabulations seemed to develop in regions of coalescent areas of RORA.

The development and progression of RORA could be tracked in MIDD patients using OCT images, allowing potential definition of novel surrogate markers. Similarities to OCT features in age-related macular degeneration, where mitochondrial dysfunction has been implicated in the pathogenesis, support wide-ranging benefits from proof-of-concept studies in MIDD.