Ellipsoid Zone Reflectivity a Promising Biomarker in iAMD

This study found that higher outer retinal reflectivity was linked to better retinal function in AMD, suggesting that ellipsoid zone reflectivity on SD-OCT could serve as a biomarker for assessing outer retinal and functional impairment. These images from the study show a healthy individual (A) and one with intermediate AMD (B). In the heat-map representation, the relative ellipsoid zone reflectivity is represented with lower and higher values ranging from red to green, while point-wise retinal sensitivity is demonstrated by superimposed specific values and also color-coded stimulus points, again with lower values in red and higher values in green. Note the association of lower rEZR values (more red-colored areas) with worse retinal function, as well as higher rEZR values (more green-colored areas) with better retinal function. Photo: Liermann YN, et al. Sci Rep. June 20, 2025. Click image to enlarge. An ongoing quest in age-related macular degeneration (AMD) research is to identify sensitive and reliable imaging biomarkers that accurately reflect retinal function. One that showed potential in a recent study is the measure of relative ellipsoid zone reflectivity (rEZR)—the ratio of peak reflectivity of the EZ to the external limiting membrane—on spectral-domain OCT, which was found to be significantly associated with various measures of retinal function and integrity in a cohort of patients with varying stages of AMD.A prospective multicenter clinical trial called MACUSTAR included 301 participants, 275 of whom were included in the final analysis. Of these, 34 had early AMD, 152 had intermediate AMD, 43 had late-stage AMD and 56 were controls. All participants underwent a comprehensive battery of functional vision tests and SD-OCT imaging to measure rEZR. The study used arbitrary units (AU) rather than absolute values to measure signal intensity.The study's findings revealed that the overall mean rEZR was 36.9 AU with early AMD patients showing higher values (41.2 AU) and late AMD patients showing significantly lower rEZR (16.3 AU). The control group had the highest rEZR at 47.8 AU. In terms of retinal function, the mean mesopic average threshold across all participants was 21.8 dB, with late-stage AMD patients recording an average of 8.0 dB.The rEZR was significantly associated with low-luminance visual acuity and Pelli-Robson contrast sensitivity, but not with BCVA. The researchers elaborated on this finding in their paper for Scientific Reports: “While patients with advanced AMD stages experience significant reduction in high-contrast, high-luminance BCVA, patients with earlier stages, specifically iAMD patients, suffer from functional impairment beyond BCVA assessment, presenting with prolonged dark adaptation, reduced contrast sensitivity, localized deficits of FCP-derived retinal sensitivity and difficulties with vision under dim light conditions,” they wrote.The strong correlations between higher rEZR values and improved retinal function observed in this study suggest that the quantitative measure could serve as a structural indicator for retinal function in AMD, which the researchers confirm is biologically plausible.“The EZ signal in SD-OCT imaging is assumed to originate from mitochondria within photoreceptors, which are essential for metabolism and health, and exhibit light-scattering properties due to their optical reflectivity,” they explained in their paper. “This reflectivity, impacted by photoreceptor function and integrity, indicates that changes in the EZ signal can reflect compromised photoreceptor function.”More analyses are necessary to gain a clearer understanding of the clinical implications of rEZR, especially regarding its prognostic significance for progression and visual impairment in AMD patients, specifically those with intermediate AMD.Click here for the journal source. Liermann YN, Behning C, Isselmann B, et al. Ellipsoid zone reflectivity as a functional imaging biomarker for age-related macular degeneration: a MACUSTAR study report. Sci Rep. June 20, 2025. [Epub ahead of print].