Early detection of tamoxifen-induced retinal injury: ellipsoid zone reflectivity as a sensitive structural marker

Abstract

Purpose To investigate early structural alterations in the outer retina and choroid of tamoxifen-treated patients without clinically detectable retinopathy by quantitatively assessing reflectivity changes of the external limiting membrane (ELM), ellipsoid zone (EZ), and retinal pigment epithelium (RPE), along with the choroidal vascularity index (CVI). Methods The study included 45 eyes of 45 tamoxifen-treated women and 50 eyes of 50 age- and sex-matched healthy female controls. ELM, EZ, and RPE reflectivity was measured along foveal, parafoveal, and perifoveal axes. CVI was derived using a standardized binarization method. Correlations between reflectivity metrics and tamoxifen exposure indices were analyzed. Results Tamoxifen users showed a marked reduction in EZ reflectivity at the central fovea and at the temporal perifovea (p = 0.005 and p = 0.037, respectively), accompanied by a corresponding decrease in relative EZ values at the central fovea and at the temporal parafovea (p = 0.012 and p = 0.039, respectively). In contrast, ELM and RPE reflectivity metrics remained stable across all evaluated regions (p > 0.05). CVI measurements revealed no significant differences between the patient and control groups (p > 0.05). Within the tamoxifen cohort, treatment duration demonstrated weak but significant positive associations with central foveal ELM reflectivity (r = 0.389, p = 0.008), whereas age was negatively correlated with EZ reflectivity in the nasal parafoveal region (r = - 0.331, p = 0.026). Conclusions Early tamoxifen exposure appears to affect the EZ before detectable alterations become evident in the ELM, RPE, or choroid. These findings suggest that subtle EZ disruption may represent an early structural indicator of tamoxifen-related retinal involvement and could potentially aid in identifying patients who may require closer monitoring. However, longitudinal studies are needed to confirm these findings and clarify their clinical significance.