OCT-based AI-assisted phenotyping of intermediate AMD in the prospective PINNACLE trial: PINNACLE Study Report 9

PINNACLE is one of the largest prospective multicentre observational studies evaluating the progression of intermediate age-related macular degeneration (iAMD). This paper aims to provide an optical coherence tomography (OCT)-based qualitative and quantitative characterisation of the cohort's baseline morphology.

Based on expert grader readings and artificial intelligence (AI)-based image analysis, we report the prevalence, quantitative measurements, topographic distribution and intercorrelation of characteristic iAMD features including drusen, drusen subtypes, subretinal drusenoid deposits (SDD), hyperreflective foci (HRF), double layer sign and various measurements of outer retinal condition, such as ellipsoid zone (EZ) and outer nuclear layer (ONL) thicknesses, incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) and a semi-automated atrophic marker including EZ loss and choroidal hypertransmission (EZLHT).

Drusen accumulate within the central 3 mm while SDD predominantly occurs in the superior perifoveal quadrant. Whereas higher drusen volume was associated with the presence and volume of HRF, it was inversely correlated with SDD presence. Thickness measurements of the EZ and ONL demonstrate outer retinal thinning, indicating photoreceptor compromise in iAMD, more pronounced in eyes showing atrophic features such as iRORA or EZLHT.

This work combines expert grader readings with AI-based image analyses, applied on the largest prospectively, densely OCT-imaged cohort of iAMD reported on so far. The results show feature distribution comparable to previous reports. They substantially contribute to the comprehensive morphological characterisation of iAMD. This data is relevant for the interpretation of longitudinal data, refining inclusion criteria for future clinical trials and for providing a reference to other trials in the field.