Ophthalmic care uncommon after tamoxifen initiation

Few people starting tamoxifen have an ophthalmic encounter in the following year, and fewer still undergo retinal imaging, a US cohort study suggests.¹ In the analysis, published online in JAMA Ophthalmology, 7.0% of individuals had an ophthalmic encounter within 12 months, and 1.7% underwent retinal optical coherence tomography (OCT) or fundus photography. Among those with breast cancer, ophthalmic use after adjustment was no greater with tamoxifen than with aromatase inhibitors.

Tamoxifen is a mainstay of adjuvant therapy for hormone receptor–positive breast cancer,² but it can damage the retina. Crystalline maculopathy, pseudocystic foveal cavitation, and cystoid macular edema have been reported in up to 12% of patients taking the standard 20-mg daily dose for at least 2 years, although estimates vary across studies.^3,4 These changes can lead to irreversible vision loss. Spectral-domain OCT can reveal subclinical structural changes before visual symptoms develop, and experts advise regular ophthalmic monitoring during therapy.^4,5

Even so, no formal screening guideline for tamoxifen exists in the US. The American Academy of Ophthalmology has issued evidence-based recommendations for hydroxychloroquine,⁶ but there is no consensus protocol for tamoxifen retinopathy. Without clear direction, the investigators suggested, oncologists may not routinely refer patients for eye examinations. Real-world data are also scarce: the only earlier population-based study, from South Korea, found that 20.4% of those taking tamoxifen had any ophthalmic examination after starting the drug and that 6.5% were screened within 1 year.⁷

To examine US practice, Siddharth Gandhi, BMSc, of Queen’s University in Kingston, Ontario, Canada, and colleagues analyzed data from the National Institutes of Health All of Us Research Program.⁸ They identified adults with a first tamoxifen prescription and at least 365 days of follow-up, excluding those taking hydroxychloroquine. Participants with breast cancer taking aromatase inhibitors, which are used for hormone receptor–positive disease but carry no recommendation for retinal toxicity screening, served as a comparison group.⁹

The cohort comprised 2,327 individuals (95.9% female; mean age, 53.8 years) taking tamoxifen, Encounters were more common among those with preexisting glaucoma or diabetic retinopathy than among those with neither condition (25.0% vs 6.3%). Greater use was associated with preexisting glaucoma (adjusted odds ratio [aOR], 3.87; 95% confidence interval (CI), 2.12-7.06), greater health care use before starting tamoxifen (aOR, 1.43; 95% CI, 1.24-1.63), and older age (aOR per 10-year increase, 1.21; 95% CI, 1.04-1.42).

Among participants with breast cancer, 6.7% of 1,886 taking tamoxifen and 8.5% of 2,809 taking aromatase inhibitors had an ophthalmic evaluation within 12 months. After adjustment, tamoxifen use was not associated with greater ophthalmic use (aOR, 1.10; 95% CI, 0.85-1.42).

The investigators concluded that structured monitoring related to tamoxifen was not readily apparent in this health care network, and that the findings support further evaluation of whether formal guidance and referral pathways could improve monitoring. The study did not assess the incidence or natural history of retinopathy, the yield or benefit of screening, visual outcomes, cost-effectiveness, or the best timing and frequency of testing. Prospective and comparative studies are therefore needed before specific screening recommendations can be made. Because several specialties prescribe tamoxifen, future work should also address communication among oncology, ophthalmology, primary care, gynecology, and other prescribing clinicians.

Gandhi commented, “What stood out to us was how little retinal-specific testing occurred after tamoxifen initiation. Only 1.7% of patients underwent retinal OCT or fundus photography within the first year, and overall ophthalmic use was no greater with tamoxifen than with aromatase inhibitors after adjustment. That suggests structured tamoxifen-specific monitoring may not be occurring consistently. The next step is to better define who is truly at risk for tamoxifen retinopathy, when toxicity develops, and whether screening improves outcomes. That evidence is what we need before establishing more specific guidance on whom to screen, when to start, and how often to test.”

References
1. Gandhi S, Balas M, Wang P, McKay BR, Kertes PJ, Martens R. Ophthalmic encounters after tamoxifen initiation. JAMA Ophthalmol. Published online October 29, 2026. doi:10.1001/jamaophthalmol.2026.4646
2. Davies C, Godwin J, Gray R, et al; Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomized trials. Lancet. 2011;378(9793):771-84. doi:10.1016/S0140-6736(11)60993-8
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5. Eisner A, Luoh SW. Breast cancer medications and vision: effects of treatments for early-stage disease. Curr Eye Res. 2011;36:867-85. doi:10.3109/02713683.2011.594202
6. Marmor MF, Kellner U, Lai TYY, Melles RB, Mieler WF; American Academy of Ophthalmology. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology. 2016;123:1386-94. doi:10.1016/j.ophtha.2016.01.058
7. Ahn SJ, Kim J, Kwon HY. Nationwide screening practices for tamoxifen retinal toxicity in South Korea: a population-based cohort study. J Clin Med. 2024;13:2167. doi:10.3390/jcm13082167
8. Denny JC, Rutter JL, Goldstein DB, et al; All of Us Research Program Investigators. The “All of Us” research program. N Engl J Med. 2019;381:668-76. doi:10.1056/NEJMsr1809937
9. Schneider R, Barakat A, Pippen J, Osborne C. Aromatase inhibitors in the treatment of breast cancer in postmenopausal female patients: an update. Breast Cancer (Dove Med Press). 2011;3:113-25. doi:10.2147/BCTT.S22905