Photoreceptor assessment in age-related macular degeneration

Clinical trials investigating drugs for various stages of age-related macular degeneration (AMD) are actively underway and there is a strong interest in outcomes that demonstrate a structure-function-correlation. The ellipsoid zone (EZ), a crucial anatomical feature affected in this disease, has emerged as a strong contender. There is significant interest in evaluating EZ metrics on Optical Coherence Tomography (OCT), such as integrity and reflectivity, as disruption of this photoreceptor-rich layer may indicate disease progression. Loss of photoreceptor integrity in the junctional zone of geographic atrophy (GA) has been shown to exceed the areas of retinal pigment epithelial (RPE) atrophy, thus predicting future GA expansion. Furthermore, reduced visual acuity and retinal sensitivity have been correlated with loss of EZ integrity, underscoring a structure-function relationship. Photoreceptor integrity has also recently been acknowledged by the Food and Drug Administration (FDA), supporting its use as a primary endpoint in clinical trials investigating treatments for GA. However, the segmentation of this EZ still poses challenges. Continuous enhancements in OCT resolution and advancements in automated segmentation algorithms contribute to improved assessment of the EZ, strengthening its potential as an imaging biomarker for assessing photoreceptor function. It remains to be seen whether the EZ will serve as a surrogate marker for intermediate AMD. This article aims to provide an overview of the current understanding and knowledge of the EZ, while addressing ongoing challenges encountered in its assessment and interpretation.