Challenges Associated With Ellipsoid Zone Intensity Measurements Using Optical Coherence Tomography

Optical coherence tomography (OCT) allows noninvasive visualization of individual retinal layers and has become a mainstay in the diagnosis and management of a wide range of retinal and systemic diseases. As the number of available treatments increases, there is growing interest in developing sensitive OCT-based biomarkers for assessing therapeutic response. In particular, the hyperreflective outer retinal band just posterior to the external limiting membrane, also known as the ellipsoid zone (EZ), is a widely used biomarker of photoreceptor structure. The integrity of the EZ, EZ lesion size, and width/area of retained EZ are established metrics that have been correlated with visual acuity and other aspects of retinal function (e.g., microperimetry and electroretinography). More recently, EZ reflectivity has emerged as a potentially more sensitive biomarker of photoreceptor structure, as reflectivity has been shown to undergo changes in retinal degenerative conditions prior to more marked changes in EZ integrity. However, multiple challenges exist that prohibit widespread clinical utilization. Interdevice variability can impact OCT image appearance due to differences in hardware, acquisition parameters, and image processing methods. In addition, image analysis practices vary widely across studies—this lack of standardization prevents robust comparison of results between studies and inhibits more widespread adoption of extracted biomarkers. Finally, there is ambiguity as to how well EZ intensity/reflectivity correlates with underlying photoreceptor structure as assessed with adaptive optics-based imaging methods. Here we review these challenges and discuss their impact on the use of EZ reflectivity measurements. Translational Relevance: Qualitative evaluation of the ellipsoid zone band on optical coherence tomography is a valuable clinical tool for assessing photoreceptor structure, though more quantitative metrics are emerging. Awareness of the challenges involved in interpreting quantitative metrics is important for their clinical translation.