Photoreceptor Disease at Ambiguous Transition Zones in Inherited Retinal Degenerations.

Purpose: Key outcome measures for inherited retinal degenerations (IRDs) are derived from the termination point of the inner and outer segment junction (IS/OS, or ellipsoid zone (EZ)) signal on optical coherence tomography (OCT), which demarcates the emergence of photoreceptor outer segment (OS) abnormalities. However, the termination point is not always abrupt and can be ambiguous. This study aimed to characterize OS disease at each retinal location.

Methods: Widefield OCTs from two ABCA4-associated and fifteen RHO-associated IRD patients were recorded over ∼2 years. Data from a neighborhood of each sample were fed into a two-level artificial intelligence architecture, which achieved 95% accuracy for classifying outer retinal disease into definitely present OS (DPOS), definitely absent OS (DAOS), or questionably absent OS (QAOS).

Results: DPOS and DAOS regions were always separated by QAOS regions; wider QAOS regions corresponded to an extended transition from OS disease to health. Point-by-point comparison of OS maps with serial widefield imaging showed that, on average, 94% of the samples remained stable, with the remainder showing progression. The best predictor of progression was the distance to the nearest locus with greater OS disease: DPOS and QAOS pixels within 2° and 5.5°, respectively, of a nearby location with greater disease had as much as 10-fold higher likelihood of progression.

Conclusions: The assumption of an abrupt transition in EZ-based outcomes may not reflect the underlying pathophysiology of IRDs.

Translational relevance: Ambiguous transition zones and their immediate neighborhoods may demarcate retinal regions having high likelihood for progression and act as efficient endpoints for clinical trials.