LAUSR

Introduction Tamoxifen, a selective estrogen antagonist, is part of standard adjuvant therapy for hormone receptor-positive breast cancer. In addition to known systemic toxicities, well-described retinotoxic effects include peripheral and macular crystalline deposits, pseudocystic foveal cavitations, as well as an increased risk of developing punctate pigmentary changes. However, the true prevalence of retinal toxicity is unclear, with the literature reporting rates between 1.5% and 11%, with significant geographic and temporal discrepancies depending on choice of screening modality. Advances in retinal imaging, specifically spectral domain and swept-source optical coherence tomography (OCT), have led to more sensitive diagnosis of toxicity. However, the field of view of commercially available OCT is limited 30 degrees, whereas ultra-widefield (UWF) imaging can image up to 200 degrees of the retina, albeit with a superficial rather than a cross-sectional view. Therefore, UWF imaging may visualize previously underreported signs of toxicity in the peripheral retina such as pigmentary changes better than macula-focused imaging alone like OCT. As such, the goals of the present study were to: 1) determine the prevalence of tamoxifen retinopathy in our cohort, a major northeastern metropolitan area, based on multimodal retinal imaging including macular OCT, fundus photos, and autofluorescence; 2) determine whether the additional field of view captured in UWF imaging contributes to the diagnosis of tamoxifen retinopathy by assessing for peripheral findings, most specifically pigmentary retinopathy. Methods This is a retrospective study of patients who visited the retina service of a single academic tertiary referral center between September 2012 and November 2021. Female patients initiated on tamoxifen for at least 6 months before their first retinal exam were identified. Patients with poor image quality, prior vitreoretinal surgery, retinal laser, or confounding pathology such as severe diabetic retinopathy were excluded. Two independent graders performed blinded review of OCT images for evidence of macular toxicity and UWF images for signs of central and peripheral toxicity, and the prevalence of the latter was compared to age- and gender-matched controls. A two-tailed t-test was used to compare ages of patients in the two cohorts. A one-tailed two proportion Z-test was used to determine if eyes in the tamoxifen cohort exhibited a greater rate of peripheral pigmentary changes. Results 252 eyes from 128 patients were included in the tamoxifen cohort, and 244 eyes from 125 patients in the control cohort. The average age at first retinal imaging in the tamoxifen cohort (61.1 ± 1.1, n=128) versus the control cohort (61.0 ± 1.3, n = 125) was not significantly different (p=0.95). 4 eyes (1.6%) from 2 patients (1.6%) had evidence of definitive tamoxifen retinopathy. One patient had crystalline maculopathy bilaterally visible on OCT and UWF imaging and another had macular pseudocystic cavitations bilaterally on OCT. Neither patient had peripheral findings on UWF. 31 eyes (12.4%) among 16 (12.5%) patients in the tamoxifen cohort displayed peripheral reticular pigmentary changes, compared to 59 eyes (24.2%) among 30 patients (24.0%) in the control group. The rate of peripheral pigmentary change in the tamoxifen cohort was not significantly greater than in the control group (p=0.99). Conclusion Only 2 patients had definitive tamoxifen retinopathy findings, which were both concentrated in the macula and clearly visible on OCT imaging. Given the absence of meaningful UWF changes, macular OCT may be the most valuable tool in diagnosing tamoxifen retinopathy. Our prevalence (1.6%) diverges from higher prevalences reported by studies screening with advanced retinal imaging (10-12%), though notably reflects a very different ethnic and geographic population compared with other work. Further large population studies are needed. Citation Format: Ethan Zhao, Kyle Kovacs. Prevalence and Spectrum of Manifestations of Tamoxifen Retinopathy as Assessed by Multimodal and Ultra-widefield Retinal Imaging [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-12-06.