Severe retinopathy induced by low-dose tamoxifen: a 10-month follow-up analysis based on multimodal imaging

Severe retinopathy induced by low-dose tamoxifen: a 10-month follow-up analysis based on multimodal imaging | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Severe retinopathy induced by low-dose tamoxifen: a 10-month follow-up analysis based on multimodal imaging Shaochi Zhang, Yuanru Wang, Yang Liu, Xiaolong Qi, Xiao Zhang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7621841/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 Nov, 2025 Read the published version in BMC Ophthalmology → Version 1 posted 12 You are reading this latest preprint version Abstract Background : Tamoxifen retinopathy (TAM-R) typically occurs with prolonged and high-dose administration. This study presents an uncommon instance of severe TAM-R following 3.75 years of low-dose tamoxifen (10mg/day) treatment, totaling 450mg cumulatively. Case Report: A 35-year-old female with obesity (BMI 47.86 kg/m²) presented with bilateral vision loss. Multimodal imaging (OCT/OCTA/FFA/FAF) revealed retinal crystal deposition, macular pseudocyst, IS/OS rupture, and deep capillary plexus loss. Despite discontinuation of medication, visual acuity remained poor (BCVA .15 right eye, .03 left eye). At the 10-month follow-up, there was partial structural improvement, yet IS/OS impairment persisted. Conclusion : This case challenges traditional TAM-R dosage thresholds, suggesting obesity may exacerbate toxicity. Baseline OCTA vascular markers correlate with irreversible visual impairment, offering novel insights for prognostic evaluation. Tamoxifen Retinal toxicity Low-dose Multimodal imaging Case Report Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Tamoxifen retinopathy is a rare adverse reaction associated with prolonged tamoxifen use, first documented in 1978, with an incidence ranging from 1.5% to 11.8%[ 1 ]. Typical tamoxifen retinopathy (TAM-R) is characterized by distinctive yellow-white crystalline deposits in the retinal nerve fiber and inner plexiform layers, along with macular pseudo cystoid edema[ 2 ], deep blood flow impairment, and irreversible vision loss. This condition typically occurs in individuals receiving high doses (≥ 60mg/day)[ 3 ] or long-term cumulative doses (> 32g) of tamoxifen[ 4 , 5 ]. Currently, challenges in the management of TAM-R include the absence of early diagnostic markers, unclear individual susceptibility factors, and uncertain disease progression and recovery post-treatment cessation. We present a unique case of severe TAM-R following the excision of an aggressive neurofibroma in the leg, where low-dose tamoxifen (10mg/day) was administered for 3 years and 9 months to prevent recurrence. Detailed documentation of structural and microvascular changes was conducted using multimodal imaging techniques (OCT/OCTA/FFA/FAF) and monitored for up to 10 months post-treatment discontinuation. The patient has provided signed written informed consent and for consented participation to and publication. This study research follow adheres to the principles of Declaration of Helsinki guidelines and has received been approval approved from by the Ethics Committee of Ningxia Hui Autonomous Region. Case Summary A 35-year-old woman presented with a gradual decline in visual acuity in both eyes over the course of a year. She had a history of receiving low-dose oral tamoxifen (10mg/day) for 3 years and 9 months (totaling 450mg) following surgery for a neurofibroma in her lower leg, with no subsequent monitoring. Ophthalmic evaluation revealed best corrected visual acuity of 20/125 in the right eye and 20/667 in the left eye, along with corneal endothelial crystallization. The fundus examination showed numerous yellow-white crystalline deposits in the posterior pole. Infrared fundus photography indicated retinal structural damage, characterized by a large area of intense high reflection signal in the posterior pole. Spectral-domain optical coherence tomography (SD-OCT) imaging revealed diffuse point-like strong reflections in the nerve fiber and inner plexiform layers with interlayer cavities, a pseudocyst cavity in the macular region, and disruption of the inner segment/outer segment junction (Fig1).Autofluorescence analysis revealed varying levels of autofluorescence in the crystalline substance deposition area of both eyes, characterized by low autofluorescence, scattered high autofluorescence, and clustered high fluorescence in the macular fovea. Fluorescein angiography (FFA) demonstrated high fluorescence in the early stages indicating macular fluorescein leakage and crystal-like substance deposition in both eyes, with pronounced vascular leakage in later stages. Additionally, fluorescence intensity decreased in the macular dye accumulation and crystal-like substance deposition area (Fig2). Optical coherence tomography angiography (OCTA) using AngioVue (Optovue, 6×6 mm scan) revealed reduced vascular density with vasodilation in the deep capillary plexus and choroid macular area, accompanied by an enlargement of the left macular avascular area (Fig3). Following the diagnosis of retinopathy, tamoxifen was promptly discontinued. A 10-month follow-up post-drug discontinuation indicated no significant changes in visual acuity, albeit a reduction in the extent of fundus crystalline deposits. OCT imaging illustrated a decrease in the range of intense reflex foci in the nerve fiber layer and inner plexiform layer, while the damage extent of the IS/OS layer expanded (Fig4). Discussion and Conclusion Tamoxifen, a selective estrogen receptor modulator, is utilized as an adjuvant endocrine therapy for estrogen receptor-positive breast cancer[6]. It also shows promise in the pharmacological management of neurofibromas by disrupting tumor metabolism, particularly in cases of recurrent disease.[4] For desmoid tumors, long-term and high-dose tamoxifen therapy (exceeding 120 mg/day) is recommended as the primary treatment. Ocular toxicity associated with tamoxifen includes retinopathy, keratopathy, and cataracts, with TAM-R being a rare clinical manifestation[5]. Typical TAM-R predominantly occurs in individuals receiving high doses (≥60 mg/day) or prolonged treatment (>32g total).This case represents a novel observation of severe tamoxifen-resistant toxic anterior segment syndrome (TAM-R) following a low daily dose of tamoxifen (10mg) over a brief period (3.75 years), contrary to the conventional cumulative threshold (>32g). Despite the low dosage, the patient exhibited pronounced lesions, possibly influenced by their obesity (BMI: 47.86 kg/m²). Elevated triglyceride levels (1.82 mmol/L) may facilitate the retention of lipophilic metabolites like 4-hydroxytamoxifen within the retinal plexiform layer. The synergistic impact of metabolic syndrome on drug potency underscores the importance of heightened vigilance among obese individuals[7]. Furthermore, we observed a phenomenon of structural and functional segregation in SD-OCT: initial data revealed a pronounced reflection focus (crystallization) in the inner plexiform layer (IPL) accompanied by disruption of the inner segment/outer segment (IS/OS) junction. However, following a 10-month cessation of medication, visual acuity remained unchanged compared to baseline. Notably, the crystalline component in the nerve fiber layer and IPL diminished, suggesting a potential restoration of phagocytic activity in Müller cells[8, 9]. Surprisingly, the area of IS/OS damage expanded beyond initial measurements, contradicting existing literature[10]. This discrepancy may be attributed to the cumulative impact of the drug. Additionally, optical coherence tomography angiography (OCTA) revealed a reduced vascular density in the deep capillary plexus (DCP) and choroidal telangiectasia, consistent with prior observations of cystic dilatation in the temporal DCP, albeit without explicit mention of choroidal hemodynamic alterations[11]. Moreover, we identified morphological alterations in the foveal avascular zone (FAZ) of the left eye, which exhibited enlargement compared to the right eye. This enlargement was directly correlated with poorer visual acuity, indicating a coherent relationship among blood flow modifications, histopathological changes, and visual dysfunction in this condition. These findings introduce a novel noninvasive parameter for evaluating visual prognosis. Currently, the efficacy of intravitreal drug administration for treating TAM-R remains uncertain. Therefore, the emphasis in TAM-R management lies in prevention. With the increasing trend of prolonged tamoxifen therapy exceeding 5 years, the potential for delayed toxicity in previously unaffected individuals emerges as a significant clinical concern[12]. Oncologists should acknowledge the necessity of retinal evaluation in patients undergoing tamoxifen therapy. In conclusion, while presenting a common case of severe retinopathy triggered by low-dose tamoxifen, this study is subject to several limitations: (1) the follow-up duration is restricted to 10 months, potentially obscuring delayed vascular recovery; (2) electrophysiological assessments were omitted due to the diagnostic and prognostic adequacy of macular structural and vascular alterations; and (3) the impact of obesity necessitates validation in a more extensive sample size. Abbreviations TAM-R Tamoxifen retinopathy SD-OCT Spectral-domain Optical Coherence Tomography FFA Fluorescein Angiography OCT-A Optical Coherence Tomography Angiography BVCA Best Visual Corrected Acuity RE Right Eye LE Left Eye IPL Inner Plexiform Layer IS/OS Inner Segment/Outer Segment DCP Deep Capillary Plexus FAZ Foveal Avascular Zone . Declarations Acknowledgments Not applicable. Authors ’ contributions ZSC: study design, analysis and interpretation of patient data. WYR: study design analysis and interpretation of patient data, drafting the manuscript. LY: data collection of patient, drafting the manuscript.QXL: data collection of patient. ZX: revising the manuscript for content, study supervision. HXL: revising the manuscript for content, study supervision. All authors read and approved the final manuscript. Funding None. Availability of data and materials All data generated or analysed during this study are included in this published article. Declarations Ethics approval and consent to participate All research was conducted following legal and ethical requirements at the ethics committee (Ethics Committee of Ningxia Hui Autonomous Region). Consent for publication Written informed consent was obtained from the patients for publication of this Case Report and any accompanying images. Competing interests The authors declare that they have no competing interests. Author details 1People's Hospital of Ningxia Hui Autonomous Region,Ningxia Medical University,China References Doshi RR, Fortun JA, Kim BT, Dubovy SR, Rosenfeld PJ. Pseudocystic foveal cavitation in tamoxifen retinopathy. Am J Ophthalmol. 2014;157:1291-1298.e3. https://doi.org/10.1016/j.ajo.2014.02.046. Doble N, Wells-Gray EM, Wells M, Choi SS. Foveal cone loss in tamoxifen maculopathy: a case report. J Med Case Rep. 2023;17:464. https://doi.org/10.1186/s13256-023-04199-z. Lazzaroni F, Scorolli L, Pizzoleo CF, Savini G, Meduri RA, Nigris AD, et al. Tamoxifen retinopathy: Does it really exist? Bonvalot S, Desai A, Coppola S, Le Péchoux C, Terrier P, Dômont J, et al. The treatment of desmoid tumors: a stepwise clinical approach. Ann Oncol: Off J Eur Soc Med Oncol. 2012;23 Suppl 10:x158-166. https://doi.org/10.1093/annonc/mds298. Hansmann A, Adolph C, Vogel T, Unger A, Moeslein G. High-dose tamoxifen and sulindac as first-line treatment for desmoid tumors. Cancer. 2004;100:612–20. https://doi.org/10.1002/cncr.11937. Eisner A, Luoh S-W. Breast cancer medications and vision: effects of treatments for early-stage disease. Curr Eye Res. 2011;36:867–85. https://doi.org/10.3109/02713683.2011.594202. Kim H-A, Lee S, Eah KS, Yoon YH. Prevalence and Risk Factors of Tamoxifen Retinopathy. Ophthalmology. 2020;127:555–7. https://doi.org/10.1016/j.ophtha.2019.10.038. Shen W, Fruttiger M, Zhu L, Chung SH, Barnett NL, Kirk JK, et al. Conditional müllercell ablation causes independent neuronal and vascular pathologies in a novel transgenic model. J Neurosci: Off J Soc Neurosci. 2012;32:15715–27. https://doi.org/10.1523/JNEUROSCI.2841-12.2012. Mäenpää H, Mannerström M, Toimela T, Salminen L, Saransaari P, Tähti H. Glutamate uptake is inhibited by tamoxifen and toremifene in cultured retinal pigment epithelial cells. Pharmacol Toxicol. 2002;91:116–22. https://doi.org/10.1034/j.1600-0773.2002.910305.x. Park YJ, Lee S, Yoon YH. One-year follow-up of optical coherence tomography angiography microvascular findings: macular telangiectasia type 2 versus tamoxifen retinopathy. Graefes Arch Clin Exp Ophthalmol. 2022;260:3479–88. https://doi.org/10.1007/s00417-022-05695-6. Bazvand F, Mahdizad Z, Mohammadi N, Shahi F, Mirghorbani M, Riazi-Esfahani H, et al. Tamoxifen retinopathy. Survey of Ophthalmology. 2023;68:628–40. https://doi.org/10.1016/j.survophthal.2023.02.003. Zamorano Martín F, Rocha-de-Lossada C, Rachwani Anil R, Borroni D, Rodriguez Calvo De Mora M, España Contreras M. Tamoxifen maculopathy: the importance of screening and long follow-up. J Fr Ophtalmol. 2020;43:727–30. https://doi.org/10.1016/j.jfo.2019.12.004. Additional Declarations No competing interests reported. Supplementary Files CAREchecklist2013.pdf Cite Share Download PDF Status: Published Journal Publication published 26 Nov, 2025 Read the published version in BMC Ophthalmology → Version 1 posted Editorial decision: Revision requested 13 Oct, 2025 Reviewers agreed at journal 08 Oct, 2025 Reviewers agreed at journal 07 Oct, 2025 Reviews received at journal 06 Oct, 2025 Reviewers agreed at journal 06 Oct, 2025 Reviews received at journal 03 Oct, 2025 Reviewers agreed at journal 02 Oct, 2025 Reviewers agreed at journal 02 Oct, 2025 Reviewers invited by journal 18 Sep, 2025 Editor assigned by journal 16 Sep, 2025 Submission checks completed at journal 16 Sep, 2025 First submitted to journal 15 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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4","display":"","copyAsset":false,"role":"figure","size":408791,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"Fig4.png","url":"https://assets-eu.researchsquare.com/files/rs-7621841/v1/5a029a17b7cb43b07b1cdb8c.png"},{"id":97178540,"identity":"a8e3910f-8d33-4932-abab-e5c0749434ac","added_by":"auto","created_at":"2025-12-01 16:10:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2249908,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7621841/v1/4c001eac-1577-4bf8-8d98-22eef27bf5d3.pdf"},{"id":92504814,"identity":"323e9694-baaa-48ca-8f89-33200bdcca97","added_by":"auto","created_at":"2025-09-30 12:23:17","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":381102,"visible":true,"origin":"","legend":"","description":"","filename":"CAREchecklist2013.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7621841/v1/4c10f90ab24437422eb3f08a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Severe retinopathy induced by low-dose tamoxifen: a 10-month follow-up analysis based on multimodal imaging","fulltext":[{"header":"Background","content":"\u003cp\u003eTamoxifen retinopathy is a rare adverse reaction associated with prolonged tamoxifen use, first documented in 1978, with an incidence ranging from 1.5% to 11.8%[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Typical tamoxifen retinopathy (TAM-R) is characterized by distinctive yellow-white crystalline deposits in the retinal nerve fiber and inner plexiform layers, along with macular pseudo cystoid edema[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], deep blood flow impairment, and irreversible vision loss. This condition typically occurs in individuals receiving high doses (\u0026ge;\u0026thinsp;60mg/day)[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] or long-term cumulative doses (\u0026gt;\u0026thinsp;32g) of tamoxifen[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Currently, challenges in the management of TAM-R include the absence of early diagnostic markers, unclear individual susceptibility factors, and uncertain disease progression and recovery post-treatment cessation. We present a unique case of severe TAM-R following the excision of an aggressive neurofibroma in the leg, where low-dose tamoxifen (10mg/day) was administered for 3 years and 9 months to prevent recurrence. Detailed documentation of structural and microvascular changes was conducted using multimodal imaging techniques (OCT/OCTA/FFA/FAF) and monitored for up to 10 months post-treatment discontinuation. The patient has provided signed written informed consent and for consented participation to and publication. This study research follow adheres to the principles of Declaration of Helsinki guidelines and has received been approval approved from by the Ethics Committee of Ningxia Hui Autonomous Region.\u003c/p\u003e"},{"header":"Case Summary","content":"\u003cp\u003eA 35-year-old woman presented with a gradual decline in visual acuity in both eyes over the course of a year. She had a history of receiving low-dose oral tamoxifen (10mg/day) for 3 years and 9 months (totaling 450mg) following surgery for a neurofibroma in her lower leg, with no subsequent monitoring. Ophthalmic evaluation revealed best corrected visual acuity of 20/125 in the right eye and 20/667 in the left eye, along with corneal endothelial crystallization. The fundus examination showed numerous yellow-white crystalline deposits in the posterior pole. Infrared fundus photography indicated retinal structural damage, characterized by a large area of intense high reflection signal in the posterior pole. Spectral-domain optical coherence tomography (SD-OCT) imaging revealed diffuse point-like strong reflections in the nerve fiber and inner plexiform layers with interlayer cavities, a pseudocyst cavity in the macular region, and disruption of the inner segment/outer segment junction (Fig1).Autofluorescence analysis revealed varying levels of autofluorescence in the crystalline substance deposition area of both eyes, characterized by low autofluorescence, scattered high autofluorescence, and clustered high fluorescence in the macular fovea. Fluorescein angiography (FFA) demonstrated high fluorescence in the early stages indicating macular fluorescein leakage and crystal-like substance deposition in both eyes, with pronounced vascular leakage in later stages. Additionally, fluorescence intensity decreased in the macular dye accumulation and crystal-like substance deposition area (Fig2). Optical coherence tomography angiography (OCTA) using AngioVue (Optovue, 6\u0026times;6 mm scan) revealed reduced vascular density with vasodilation in the deep capillary plexus and choroid macular area, accompanied by an enlargement of the left macular avascular area (Fig3). Following the diagnosis of retinopathy, tamoxifen was promptly discontinued. A 10-month follow-up post-drug discontinuation indicated no significant changes in visual acuity, albeit a reduction in the extent of fundus crystalline deposits. OCT imaging illustrated a decrease in the range of intense reflex foci in the nerve fiber layer and inner plexiform layer, while the damage extent of the IS/OS layer expanded (Fig4).\u003c/p\u003e"},{"header":"Discussion and Conclusion","content":"\u003cp\u003eTamoxifen, a selective estrogen receptor modulator, is utilized as an adjuvant endocrine therapy for estrogen receptor-positive breast cancer[6]. It also shows promise in the pharmacological management of neurofibromas by disrupting tumor metabolism, particularly in cases of recurrent disease.[4] For desmoid tumors, long-term and high-dose tamoxifen therapy (exceeding 120 mg/day) is recommended as the primary treatment. Ocular toxicity associated with tamoxifen includes retinopathy, keratopathy, and cataracts, with TAM-R being a rare clinical manifestation[5]. Typical TAM-R predominantly occurs in individuals receiving high doses (≥60 mg/day) or prolonged treatment (\u0026gt;32g total).This case represents a novel observation of severe tamoxifen-resistant toxic anterior segment syndrome (TAM-R) following a low daily dose of tamoxifen (10mg) over a brief period (3.75 years), contrary to the conventional cumulative threshold (\u0026gt;32g). Despite the low dosage, the patient exhibited pronounced lesions, possibly influenced by their obesity (BMI: 47.86 kg/m²). Elevated triglyceride levels (1.82 mmol/L) may facilitate the retention of lipophilic metabolites like 4-hydroxytamoxifen within the retinal plexiform layer. The synergistic impact of metabolic syndrome on drug potency underscores the importance of heightened vigilance among obese individuals[7]. Furthermore, we observed a phenomenon of structural and functional segregation in SD-OCT: initial data revealed a pronounced reflection focus (crystallization) in the inner plexiform layer (IPL) accompanied by disruption of the inner segment/outer segment (IS/OS) junction. However, following a 10-month cessation of medication, visual acuity remained unchanged compared to baseline. Notably, the crystalline component in the nerve fiber layer and IPL diminished, suggesting a potential restoration of phagocytic activity in Müller cells[8, 9]. Surprisingly, the area of IS/OS damage expanded beyond initial measurements, contradicting existing literature[10]. This discrepancy may be attributed to the cumulative impact of the drug. Additionally, optical coherence tomography angiography (OCTA) revealed a reduced vascular density in the deep capillary plexus (DCP) and choroidal telangiectasia, consistent with prior observations of cystic dilatation in the temporal DCP, albeit without explicit mention of choroidal hemodynamic alterations[11]. Moreover, we identified morphological alterations in the foveal avascular zone (FAZ) of the left eye, which exhibited enlargement compared to the right eye. This enlargement was directly correlated with poorer visual acuity, indicating a coherent relationship among blood flow modifications, histopathological changes, and visual dysfunction in this condition. These findings introduce a novel noninvasive parameter for evaluating visual prognosis.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; Currently, the efficacy of intravitreal drug administration for treating TAM-R remains uncertain. Therefore, the emphasis in TAM-R management lies in prevention. With the increasing trend of prolonged tamoxifen therapy exceeding 5 years, the potential for delayed toxicity in previously unaffected individuals emerges as a significant clinical concern[12]. Oncologists should acknowledge the necessity of retinal evaluation in patients undergoing tamoxifen therapy.\u003c/p\u003e\n\u003cp\u003eIn conclusion, while presenting a common case of severe retinopathy triggered by low-dose tamoxifen, this study is subject to several limitations: (1) the follow-up duration is restricted to 10 months, potentially obscuring delayed vascular recovery; (2) electrophysiological assessments were omitted due to the diagnostic and prognostic adequacy of macular structural and vascular alterations; and (3) the impact of obesity necessitates validation in a more extensive sample size.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTAM-R\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eTamoxifen retinopathy\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSD-OCT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eSpectral-domain Optical Coherence Tomography\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eFFA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eFluorescein Angiography\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eOCT-A\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eOptical Coherence Tomography Angiography\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eBVCA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eBest Visual Corrected Acuity\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eRE\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eRight Eye\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eLE\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eLeft Eye\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIPL\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eInner Plexiform Layer\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIS/OS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eInner Segment/Outer Segment\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eDCP\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eDeep Capillary Plexus\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eFAZ\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eFoveal Avascular Zone .\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u003c/strong\u003e\u003cstrong\u003e’\u003c/strong\u003e\u003cstrong\u003econtributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZSC: study design, analysis and interpretation of patient data. WYR: study design analysis and interpretation of patient data, drafting the manuscript. LY: data collection of patient, drafting the manuscript.QXL: data collection of patient. ZX: revising the manuscript for content, study supervision. HXL: revising the manuscript for content, study supervision. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eAll research was conducted following legal and ethical requirements at the ethics committee (Ethics Committee of Ningxia Hui Autonomous Region).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patients for publication of this Case Report and any accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1People's Hospital of Ningxia Hui Autonomous Region,Ningxia Medical University,China\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDoshi RR, Fortun JA, Kim BT, Dubovy SR, Rosenfeld PJ. Pseudocystic foveal cavitation in tamoxifen retinopathy. Am J Ophthalmol. 2014;157:1291-1298.e3. https://doi.org/10.1016/j.ajo.2014.02.046.\u003c/li\u003e\n\u003cli\u003eDoble N, Wells-Gray EM, Wells M, Choi SS. Foveal cone loss in tamoxifen maculopathy: a case report. J Med Case Rep. 2023;17:464. https://doi.org/10.1186/s13256-023-04199-z.\u003c/li\u003e\n\u003cli\u003eLazzaroni F, Scorolli L, Pizzoleo CF, Savini G, Meduri RA, Nigris AD, et al. Tamoxifen retinopathy: Does it really exist?\u003c/li\u003e\n\u003cli\u003eBonvalot S, Desai A, Coppola S, Le P\u0026eacute;choux C, Terrier P, D\u0026ocirc;mont J, et al. The treatment of desmoid tumors: a stepwise clinical approach. Ann Oncol: Off J Eur Soc Med Oncol. 2012;23 Suppl 10:x158-166. https://doi.org/10.1093/annonc/mds298.\u003c/li\u003e\n\u003cli\u003eHansmann A, Adolph C, Vogel T, Unger A, Moeslein G. High-dose tamoxifen and sulindac as first-line treatment for desmoid tumors. Cancer. 2004;100:612\u0026ndash;20. https://doi.org/10.1002/cncr.11937.\u003c/li\u003e\n\u003cli\u003eEisner A, Luoh S-W. Breast cancer medications and vision: effects of treatments for early-stage disease. Curr Eye Res. 2011;36:867\u0026ndash;85. https://doi.org/10.3109/02713683.2011.594202.\u003c/li\u003e\n\u003cli\u003eKim H-A, Lee S, Eah KS, Yoon YH. Prevalence and Risk Factors of Tamoxifen Retinopathy. Ophthalmology. 2020;127:555\u0026ndash;7. https://doi.org/10.1016/j.ophtha.2019.10.038.\u003c/li\u003e\n\u003cli\u003eShen W, Fruttiger M, Zhu L, Chung SH, Barnett NL, Kirk JK, et al. Conditional m\u0026uuml;llercell ablation causes independent neuronal and vascular pathologies in a novel transgenic model. J Neurosci: Off J Soc Neurosci. 2012;32:15715\u0026ndash;27. https://doi.org/10.1523/JNEUROSCI.2841-12.2012.\u003c/li\u003e\n\u003cli\u003eM\u0026auml;enp\u0026auml;\u0026auml; H, Mannerstr\u0026ouml;m M, Toimela T, Salminen L, Saransaari P, T\u0026auml;hti H. Glutamate uptake is inhibited by tamoxifen and toremifene in cultured retinal pigment epithelial cells. Pharmacol Toxicol. 2002;91:116\u0026ndash;22. https://doi.org/10.1034/j.1600-0773.2002.910305.x.\u003c/li\u003e\n\u003cli\u003ePark YJ, Lee S, Yoon YH. One-year follow-up of optical coherence tomography angiography microvascular findings: macular telangiectasia type 2 versus tamoxifen retinopathy. Graefes Arch Clin Exp Ophthalmol. 2022;260:3479\u0026ndash;88. https://doi.org/10.1007/s00417-022-05695-6.\u003c/li\u003e\n\u003cli\u003eBazvand F, Mahdizad Z, Mohammadi N, Shahi F, Mirghorbani M, Riazi-Esfahani H, et al. Tamoxifen retinopathy. Survey of Ophthalmology. 2023;68:628\u0026ndash;40. https://doi.org/10.1016/j.survophthal.2023.02.003.\u003c/li\u003e\n\u003cli\u003eZamorano Mart\u0026iacute;n F, Rocha-de-Lossada C, Rachwani Anil R, Borroni D, Rodriguez Calvo De Mora M, Espa\u0026ntilde;a Contreras M. Tamoxifen maculopathy: the importance of screening and long follow-up. J Fr Ophtalmol. 2020;43:727\u0026ndash;30. https://doi.org/10.1016/j.jfo.2019.12.004.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Tamoxifen, Retinal toxicity, Low-dose, Multimodal imaging, Case Report","lastPublishedDoi":"10.21203/rs.3.rs-7621841/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7621841/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Tamoxifen retinopathy (TAM-R) typically occurs with prolonged and high-dose administration. This study presents an uncommon instance of severe TAM-R following 3.75 years of low-dose tamoxifen (10mg/day) treatment, totaling 450mg cumulatively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase Report:\u003c/strong\u003e A 35-year-old female with obesity (BMI 47.86 kg/m²) presented with bilateral vision loss. Multimodal imaging (OCT/OCTA/FFA/FAF) revealed retinal crystal deposition, macular pseudocyst, IS/OS rupture, and deep capillary plexus loss. Despite discontinuation of medication, visual acuity remained poor (BCVA .15 right eye, .03 left eye). At the 10-month follow-up, there was partial structural improvement, yet IS/OS impairment persisted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: This case challenges traditional TAM-R dosage thresholds, suggesting obesity may exacerbate toxicity. Baseline OCTA vascular markers correlate with irreversible visual impairment, offering novel insights for prognostic evaluation.\u003c/p\u003e","manuscriptTitle":"Severe retinopathy induced by low-dose tamoxifen: a 10-month follow-up analysis based on multimodal imaging","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-30 12:23:12","doi":"10.21203/rs.3.rs-7621841/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-13T07:10:34+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"185215498367022187678329329541950636849","date":"2025-10-08T20:38:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"230375039613110079952714300175987438022","date":"2025-10-07T20:41:25+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-06T11:08:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"31254940067117457103131278968472127299","date":"2025-10-06T08:33:30+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-03T12:18:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"269003128143691743249523307079735618555","date":"2025-10-02T14:37:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"157309930989401265247066748369337041817","date":"2025-10-02T11:16:42+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-19T01:27:42+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-16T11:26:48+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-16T11:25:51+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Ophthalmology","date":"2025-09-15T14:35:22+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"85629988-cef4-4f61-ab15-6a2dcea73d66","owner":[],"postedDate":"September 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-01T16:03:45+00:00","versionOfRecord":{"articleIdentity":"rs-7621841","link":"https://doi.org/10.1186/s12886-025-04499-6","journal":{"identity":"bmc-ophthalmology","isVorOnly":false,"title":"BMC Ophthalmology"},"publishedOn":"2025-11-26 15:58:14","publishedOnDateReadable":"November 26th, 2025"},"versionCreatedAt":"2025-09-30 12:23:12","video":"","vorDoi":"10.1186/s12886-025-04499-6","vorDoiUrl":"https://doi.org/10.1186/s12886-025-04499-6","workflowStages":[]},"version":"v1","identity":"rs-7621841","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7621841","identity":"rs-7621841","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}