Toxic maculopathy associated with systemic Carboplatin therapy

Toxic maculopathy associated with systemic Carboplatin therapy | 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 Toxic maculopathy associated with systemic Carboplatin therapy Pauline Rizzuto, Antonin Rocher, Laurent Kodjikian, Emmanuel Grolleau, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8541064/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 16 You are reading this latest preprint version Abstract Purpose To describe a case of carboplatin-induced macular toxicity occurring during systemic treatment for metastatic non–small cell lung cancer (NSCLC). Methods Retrospective case report with a literature review. Results A 48-year-old man developed bilateral vision loss one week after receiving a second cycle of chemoimmunotherapy consisting of carboplatin, pemetrexed, and pembrolizumab administered intravenously every four weeks. Clinical evaluation revealed rapidly progressive bilateral visual decline with a central scotoma. Multimodal imaging demonstrated foveal hyperautofluorescence and disruption of the foveal ellipsoid zone in both eyes. Electrophysiological testing showed foveal peak impairment on multifocal ERG, consistent with a toxic mechanism. Ocular and systemic findings were not suggestive of a paraneoplastic process. Following discontinuation of carboplatin, anatomical and functional abnormalities stabilized. Conclusion Carboplatin-induced toxic maculopathy is rare and may result in visual acuity loss. Multimodal imaging indicates involvement of foveal photoreceptor. The reversibility of structural and functional changes after treatment cessation remains uncertain. Carboplatin chemotherapy lung cancer macular toxicity case report Figures Figure 1 Figure 2 INTRODUCTION Carboplatin is a cytotoxic alkylating agent belonging to the platinum analogue family, widely used in the treatment of numerous malignancies, including advanced ovarian carcinoma and metastatic non-small cell lung cancer (NSCLC) ( 1 ). The most commonly used agents in this class are cisplatin and carboplatin. Their mechanism of action involves alkylation of nucleic acids resulting in DNA strand breaks and crosslinking that ultimately disrupt DNA replication and RNA transcription, leading to apoptosis in tumor cells ( 2 ). In addition to binding purine bases, platinum analogues induce oxidative stress through activation of cellular detoxification pathways ( 3 ). The organs most frequently affected by platinum-related toxicity include the kidneys, liver, heart, auditory system, and peripheral nervous system. Various ophthalmic adverse effects have been reported such as papilledema, optic neuritis, orbital inflammation, and macular pigmentary changes ( 3 , 4 ). Carboplatin is generally better tolerated and associated with fewer non-hematologic complication ( 5 ). Its main toxicities involve myelosuppression, including anemia, thrombocytopenia, and neutropenia. In contrast to cisplatin, only a few cases of ocular toxicity related to carboplatin have been described, most of them involving the optic nerve ( 6 – 8 ). We report a case of carboplatin-associated toxic maculopathy in a patient undergoing systemic treatment for metastatic NSCLC. REPORT OF A CASE A 49-year-old man with stage IIIC NSCLC, diagnosed in January 2025 after evaluation of a right supraclavicular lymphadenopathy complicated by macrophage activation syndrome, received two cycles of chemoimmunotherapy consisting of carboplatin (400 mg/m2), permetrexed, (500 mg), and pembrolizumab (200 mg administered four weeks apart). Due to his general condition, he received 800 mg of carboplatin at each treatment. His past medical history included well-controlled hypertension, dyslipidemia, and asthma, with no prior ocular history. Three days after the first treatment, he noted blurred vision, bilateral ocular redness and discomfort. Following the second cycle he experienced progressive worsening of bilateral visual impairment. An ophthalmologist assessment was performed two weeks later. Best-corrected visual acuity (BCVA) measured 20/25 in the right eye and 20/30 in the left eye. Intraocular pressures were 15 mmHg and 17 mmHg, respectively, with no relative afferent pupillary defect. Fundus examinations were unremarkable. Fundus autofluorescence (FAF) imaging revealed foveal hyperautofluorence. Spectral-domain optical coherence tomography (SD-OCT) demonstrated irregularity and disruption of the foveal ellipsoid zone in both eyes, with the nasal peripapillary ellipsoid zone remained intact (Fig. 1 ). Fundus autofluorescence (FAF, left) and foveal B-scan spectral-domain optical coherence tomography (SD-OCT, right) of both eyes demonstrating foveal hyperautofluorescence on FAF, corresponding to ellipsoid zone alterations on SD-OCT (white arrow) Automated static perimetry showed relative central scotomas with reduced foveal threshold (Fig. 2 ). Humphrey automated static visual field (up, VF) and multifocal electroretinogram (down, mERG) of both eyes showing central relative scotoma on VF corresponding to foveal peak impairment on mERG (blue depression) Full-field electroretinogram (ffERG), recorded according to ISCEV standards protocol, showed normal scotopic and photopic ERG waveforms with normal amplitudes and implicit times in each type of stimulation (DA [dark adaptation] 0.01, DA 3.0, DA 10, DA oscillatory potentials, LA [light adaptation] 3.0 and LA 30 Hz flicker ERG) which confirms the absence of generalized retinal dysfunction. In contrast, multifocal electroretinogram (mERG) demonstrated severe reduced amplitude in the foveal and paracentral retinal areas corresponding to the macula, confirming the diagnosis of isolated maculopathy (Fig. 2 ). Systemic oncologic evaluation showed no evidence of cancer recurrence, and the underlying disease appeared controlled. Blood samples for anti-recoverin and anti-neuronal antibodies were negative. Given strong suspicion of carboplatin-induced maculopathy, carboplatin was discontinued, and treatment was continued with permetrexed and pembrolizumab. One month after discontinuation, BCVA showed slight further deterioration before stabilizing., At 5 months of follow-up. BCVA was 20/30 in both eyes. FAF imaging, SD-OCT, perimetry, and mERG findings remained unchanged from initial presentation. DISCUSSION Ocular adverse events from systemic anticancer therapies may significantly impair quality of life. Advances in multimodal imaging have improved early detection of chemotherapy-induced retinal toxicity. In this case, several alternative causes of acute visual loss were considered. Cancer-associated retinopathy (CAR) is a rare paraneoplastic retinopathy caused by antitumor autoantibodies, typically presenting with widespread retinal dysfunction ( 9 ). The diagnosis relies on clinical, imaging, and serologic findings in the context of malignancy ( 10 ). Anti-recoverin and anti-neuronal antibodies were negative in our patient, and the electrophysiological pattern was inconsistent with CAR, which typically affects both cone and rod pathways ( 11 ). Neither of the two other agents used—pemetrexed and pembrolizumab—has been associated with foveal toxicity. Pemetrexed may induce ocular surface disease ( 12 ), while pembroliuzumab is known to cause ocular surface inflammation or uveitis ( 13 ), but retinal toxicity has not been reported. Cisplatin is associated with several ocular toxicities, including optic neuropathy and ischemic events ( 3 , 4 , 14 ), whereas carboplatin is considered better tolerated. Reported ocular complications of carboplatin involve papilledema or optic neuropathy, sometimes resulting in irreversible vision loss ( 6 – 8 ). The mechanism of carboplatin-induced photoreceptor toxicity remains unclear. Possible pathways include excess oxidative stress or microvascular thrombotic events ( 15 ). In our patient, multimodal imaging strongly suggested foveal photoreceptor involvement: disruption of the ellipsoid zone on SD-OCT with corresponding hyperautofluorescence on FAF, a pattern reminiscent of dysfunction of photoreceptors and the retinal pigment epithelium (RPE), as observed in vitelliform-like changes. mERG confirmed the focal nature of this dysfunction, limited to the central macula where cone density is highest. The stabilization of visual function and structural abnormalities after discontinuation of carboplatin further supports a causal association, although recovery remained incomplete. This report is limited by the absence of a baseline ophthalmic examination, preventing exclusion of a preexisting macular condition. Although pemetrexed and pembrolizumab are not known to induce retinal toxicity, a potential additive or synergistic effect cannot be ruled out. CONCLUSION This case represents, to our knowledge, the first description of carboplatin-associated foveal photoreceptor toxicity. Awareness of this rare complication is essential for oncologists and ophthalmologists. Early identification and prompt cessation of the offending agent may prevent further deterioration and preserve quality of life. LIST OF ABBREVATIONS BCVA : Best-corrected visual acuity CAR : Cancer-associated retinopathy DA : Dark adaptation ERG : Electroretinogram FAF : Fundus autofluorescence ffERG : Full-field electroretinogram ISCEV : International Society for Clinical Electrophysiology of Vision LA : Light adaptation mERG : Multifocal electroretinogram NSCLC : Non–small cell lung cancer OCT : Optical coherence tomography RPE : Retinal pigment epithelium SD-OCT : Spectral-domain optical coherence tomography VF : Visual Field Declarations Ethics approval and consent to participate Research all methods were performed in accordance with the Declaration of Helsinki. An international review board approved the study (Ethics Committee of the French Society of Ophthalmology, IRB 00008855 Société Française d’Ophtalmologie IRB#1). Written informed consent was obtained from the patient. Methods and Ethical Approval All methods were performed in accordance with the relevant guidelines and regulations of the Ethics Committee of the French Society of Ophthalmology, IRB 00008855 Société Française d’Ophtalmologie IRB#1 Research all methods were performed in accordance with the Declaration of Helsinki. An international review board approved the study (Ethics Committee of the French Society of Ophthalmology, IRB 00008855 Société Française d’Ophtalmologie IRB#1). Consent for publication Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. Availability of data and material The data supporting the findings of this study are available from the corresponding author upon reasonable request. Competing interests The authors declare that they have no link of interest concerning this article. Funding The authors received no specific funding for this work. Authors' contributions PR drafted the original version of the manuscript. PR, AR and TM collected, analyzed and interpreted the patient data. They are major contributors in writing the manuscript. EG participated in the patient's therapeutic care. LA participated in the electrophysiological analysis. All authors read and approved the final manuscript. Acknowledgements The authors thank the patient for providing written informed consent for the publication of this case report. Disclosure: None References Rossi A, Di Maio M. Platinum-based chemotherapy in advanced non-small-cell lung cancer: optimal number of treatment cycles. Expert Review of Anticancer Therapy. 2016 June 2;16(6):653–60. Schmid KE, Kornek GV, Scheithauer W, Binder S. Update on Ocular Complications of Systemic Cancer Chemotherapy. Survey of Ophthalmology. 2006 Jan;51(1):19–40. Oun R, Moussa YE, Wheate NJ. The side effects of platinum-based chemotherapy drugs: a review for chemists. Dalton Trans. 2018;47(19):6645–53. Dulz S, Asselborn NH, Dieckmann KP, Matthies C, Wagner W, Weidmann J, et al. Retinal toxicity after cisplatin-based chemotherapy in patients with germ cell cancer. J Cancer Res Clin Oncol. 2017 July;143(7):1319–25. Azar I, Yazdanpanah O, Jang H, Austin A, Kim S, Chi J, et al. Comparison of Carboplatin With Cisplatin in Small Cell Lung Cancer in US Veterans. JAMA Netw Open. 2022 Oct 20;5(10):e2237699. Maleki A, Lagrew M, Slaney E. Bilateral Optic Neuropathy Secondary to Intravenous Carboplatin Therapy. JOVR. 2024 Mar 10;19(1):133–6. Shihadeh S, Patrick MM, Postma G, Trokthi B, Maitland C. Blinding Optic Neuropathy Associated With Carboplatin Therapy: A Case Report and Literature Review. Cureus [Internet]. 2024 Jan 26 [cited 2025 Aug 25]; Available from: https://www.cureus.com/articles/196393-blinding-optic-neuropathy-associated-with-carboplatin-therapy-a-case-report-and-literature-review Lewis P, Waqar S, Yiannakis D, Raman V. Unilateral Optic Disc Papilloedema following Administration of Carboplatin Chemotherapy for Ovarian Carcinoma. Case Rep Oncol. 2014 Jan 10;7(1):29–32. Cancer-associated retinopathy: an autoimmune retinopathy. Univ Med. 2010 25;29(1):56–64. Mohamed Q. Acute Optical Coherence Tomographic Findings in Cancer-Associated Retinopathy. Arch Ophthalmol. 2007 Aug 1;125(8):1132. Wei MM, Armbrust KR, Jeffrey BG, Sen HN. Cancer-Associated Retinopathy. In: Gupta V, Nguyen QD, LeHoang P, Agarwal A, editors. The Uveitis Atlas [Internet]. New Delhi: Springer India; 2020. p. 605–18. Available from: https://doi.org/10.1007/978-81-322-2410-5_102 Jung YD, Lee SB, Jung YW, Song JS, Woo IS. Epiphora following chemotherapy with pemetrexed in patients with advanced non-small cell lung cancer. Korean J Intern Med. 2017 Sept 1;32(5):923–5. Fortes BH, Liou H, Dalvin LA. Ophthalmic adverse effects of immune checkpoint inhibitors: the Mayo Clinic experience. Br J Ophthalmol. 2021 Sept;105(9):1263–71. Togna GI, Togna AR, Franconi M, Caprino L. Cisplatin Triggers Platelet Activation. Thrombosis Research. 2000 Sept;99(5):503–9. Chiang TK, White KM, Kurup SK, Yu M. Use of Visual Electrophysiology to Monitor Retinal and Optic Nerve Toxicity. Biomolecules. 2022 Sept 29;12(10):1390. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8541064","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":581907813,"identity":"1353dff3-6601-46ad-94c9-05cac76c73b8","order_by":0,"name":"Pauline Rizzuto","email":"","orcid":"","institution":"Hôpital Universitaire de la Croix-Rousse, Hospices Civils de Lyon","correspondingAuthor":false,"prefix":"","firstName":"Pauline","middleName":"","lastName":"Rizzuto","suffix":""},{"id":581907814,"identity":"039b22b8-5e83-4cd3-84ee-9207605a030a","order_by":1,"name":"Antonin Rocher","email":"","orcid":"","institution":"Hôpital Universitaire 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11:53:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8541064/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8541064/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101436792,"identity":"109bb797-28ce-431b-af11-2b263f06c6d6","added_by":"auto","created_at":"2026-01-29 16:26:06","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":681209,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFundus autofluorescence and foveal B-scan spectral-domain optical coherence tomography of both eyes\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8541064/v1/e4f0dc2dae01c6b1afd9eeec.png"},{"id":101436886,"identity":"92167d15-2096-4ccf-9633-e6161b778367","added_by":"auto","created_at":"2026-01-29 16:26:43","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":293930,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHumphrey automated static visual field and multifocal electroretinogram of both eyes\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8541064/v1/f6ba0ec546e7b60cd51c33e7.png"},{"id":101436943,"identity":"b6895f7d-c148-4311-ae3d-c53066af2a4b","added_by":"auto","created_at":"2026-01-29 16:26:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1330924,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8541064/v1/6020f4b8-c3fc-4454-a258-588db1333ecd.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Toxic maculopathy associated with systemic Carboplatin therapy","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eCarboplatin is a cytotoxic alkylating agent belonging to the platinum analogue family, widely used in the treatment of numerous malignancies, including advanced ovarian carcinoma and metastatic non-small cell lung cancer (NSCLC) (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The most commonly used agents in this class are cisplatin and carboplatin. Their mechanism of action involves alkylation of nucleic acids resulting in DNA strand breaks and crosslinking that ultimately disrupt DNA replication and RNA transcription, leading to apoptosis in tumor cells (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). In addition to binding purine bases, platinum analogues induce oxidative stress through activation of cellular detoxification pathways (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe organs most frequently affected by platinum-related toxicity include the kidneys, liver, heart, auditory system, and peripheral nervous system. Various ophthalmic adverse effects have been reported such as papilledema, optic neuritis, orbital inflammation, and macular pigmentary changes (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Carboplatin is generally better tolerated and associated with fewer non-hematologic complication (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Its main toxicities involve myelosuppression, including anemia, thrombocytopenia, and neutropenia. In contrast to cisplatin, only a few cases of ocular toxicity related to carboplatin have been described, most of them involving the optic nerve (\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWe report a case of carboplatin-associated toxic maculopathy in a patient undergoing systemic treatment for metastatic NSCLC.\u003c/p\u003e"},{"header":"REPORT OF A CASE","content":"\u003cp\u003eA 49-year-old man with stage IIIC NSCLC, diagnosed in January 2025 after evaluation of a right supraclavicular lymphadenopathy complicated by macrophage activation syndrome, received two cycles of chemoimmunotherapy consisting of carboplatin (400 mg/m2), permetrexed, (500 mg), and pembrolizumab (200 mg administered four weeks apart). Due to his general condition, he received 800 mg of carboplatin at each treatment. His past medical history included well-controlled hypertension, dyslipidemia, and asthma, with no prior ocular history.\u003c/p\u003e \u003cp\u003eThree days after the first treatment, he noted blurred vision, bilateral ocular redness and discomfort. Following the second cycle he experienced progressive worsening of bilateral visual impairment. An ophthalmologist assessment was performed two weeks later.\u003c/p\u003e \u003cp\u003eBest-corrected visual acuity (BCVA) measured 20/25 in the right eye and 20/30 in the left eye. Intraocular pressures were 15 mmHg and 17 mmHg, respectively, with no relative afferent pupillary defect. Fundus examinations were unremarkable. Fundus autofluorescence (FAF) imaging revealed foveal hyperautofluorence. Spectral-domain optical coherence tomography (SD-OCT) demonstrated irregularity and disruption of the foveal ellipsoid zone in both eyes, with the nasal peripapillary ellipsoid zone remained intact (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFundus autofluorescence (FAF, left) and foveal B-scan spectral-domain optical coherence tomography (SD-OCT, right) of both eyes demonstrating foveal hyperautofluorescence on FAF, corresponding to ellipsoid zone alterations on SD-OCT (white arrow)\u003c/p\u003e \u003cp\u003eAutomated static perimetry showed relative central scotomas with reduced foveal threshold (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eHumphrey automated static visual field (up, VF) and multifocal electroretinogram (down, mERG) of both eyes showing central relative scotoma on VF corresponding to foveal peak impairment on mERG (blue depression)\u003c/p\u003e \u003cp\u003eFull-field electroretinogram (ffERG), recorded according to ISCEV standards protocol, showed normal scotopic and photopic ERG waveforms with normal amplitudes and implicit times in each type of stimulation (DA [dark adaptation] 0.01, DA 3.0, DA 10, DA oscillatory potentials, LA [light adaptation] 3.0 and LA 30 Hz flicker ERG) which confirms the absence of generalized retinal dysfunction. In contrast, multifocal electroretinogram (mERG) demonstrated severe reduced amplitude in the foveal and paracentral retinal areas corresponding to the macula, confirming the diagnosis of isolated maculopathy (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSystemic oncologic evaluation showed no evidence of cancer recurrence, and the underlying disease appeared controlled. Blood samples for anti-recoverin and anti-neuronal antibodies were negative. Given strong suspicion of carboplatin-induced maculopathy, carboplatin was discontinued, and treatment was continued with permetrexed and pembrolizumab.\u003c/p\u003e \u003cp\u003eOne month after discontinuation, BCVA showed slight further deterioration before stabilizing., At 5 months of follow-up. BCVA was 20/30 in both eyes. FAF imaging, SD-OCT, perimetry, and mERG findings remained unchanged from initial presentation.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eOcular adverse events from systemic anticancer therapies may significantly impair quality of life. Advances in multimodal imaging have improved early detection of chemotherapy-induced retinal toxicity. In this case, several alternative causes of acute visual loss were considered. Cancer-associated retinopathy (CAR) is a rare paraneoplastic retinopathy caused by antitumor autoantibodies, typically presenting with widespread retinal dysfunction (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). The diagnosis relies on clinical, imaging, and serologic findings in the context of malignancy (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Anti-recoverin and anti-neuronal antibodies were negative in our patient, and the electrophysiological pattern was inconsistent with CAR, which typically affects both cone and rod pathways (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eNeither of the two other agents used\u0026mdash;pemetrexed and pembrolizumab\u0026mdash;has been associated with foveal toxicity. Pemetrexed may induce ocular surface disease (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e), while pembroliuzumab is known to cause ocular surface inflammation or uveitis (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e), but retinal toxicity has not been reported.\u003c/p\u003e \u003cp\u003eCisplatin is associated with several ocular toxicities, including optic neuropathy and ischemic events (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e), whereas carboplatin is considered better tolerated. Reported ocular complications of carboplatin involve papilledema or optic neuropathy, sometimes resulting in irreversible vision loss (\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe mechanism of carboplatin-induced photoreceptor toxicity remains unclear. Possible pathways include excess oxidative stress or microvascular thrombotic events (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). In our patient, multimodal imaging strongly suggested foveal photoreceptor involvement: disruption of the ellipsoid zone on SD-OCT with corresponding hyperautofluorescence on FAF, a pattern reminiscent of dysfunction of photoreceptors and the retinal pigment epithelium (RPE), as observed in vitelliform-like changes. mERG confirmed the focal nature of this dysfunction, limited to the central macula where cone density is highest. The stabilization of visual function and structural abnormalities after discontinuation of carboplatin further supports a causal association, although recovery remained incomplete.\u003c/p\u003e \u003cp\u003eThis report is limited by the absence of a baseline ophthalmic examination, preventing exclusion of a preexisting macular condition. Although pemetrexed and pembrolizumab are not known to induce retinal toxicity, a potential additive or synergistic effect cannot be ruled out.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThis case represents, to our knowledge, the first description of carboplatin-associated foveal photoreceptor toxicity. Awareness of this rare complication is essential for oncologists and ophthalmologists. Early identification and prompt cessation of the offending agent may prevent further deterioration and preserve quality of life.\u003c/p\u003e"},{"header":"LIST OF ABBREVATIONS","content":"\u003cul\u003e\n \u003cli\u003e \u003cstrong\u003eBCVA\u003c/strong\u003e: Best-corrected visual acuity\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;\u003cstrong\u003eCAR\u003c/strong\u003e: Cancer-associated retinopathy\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;\u003cstrong\u003eDA\u003c/strong\u003e: Dark adaptation\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;\u003cstrong\u003eERG\u003c/strong\u003e: Electroretinogram\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;\u003cstrong\u003eFAF\u003c/strong\u003e: Fundus autofluorescence\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;\u003cstrong\u003effERG\u003c/strong\u003e: Full-field electroretinogram\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;\u003cstrong\u003eISCEV\u003c/strong\u003e: International Society for Clinical Electrophysiology of Vision\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;\u003cstrong\u003eLA\u003c/strong\u003e: Light adaptation\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;\u003cstrong\u003emERG\u003c/strong\u003e: Multifocal electroretinogram\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;\u003cstrong\u003eNSCLC\u003c/strong\u003e: Non\u0026ndash;small cell lung cancer\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;\u003cstrong\u003eOCT\u003c/strong\u003e: Optical coherence tomography\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;\u003cstrong\u003eRPE\u003c/strong\u003e: Retinal pigment epithelium\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;\u003cstrong\u003eSD-OCT\u003c/strong\u003e: Spectral-domain optical coherence tomography\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;\u003cstrong\u003eVF\u003c/strong\u003e: Visual Field \u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eResearch all methods were performed in accordance with the Declaration of Helsinki. An international review board approved the study (Ethics Committee of the French Society of Ophthalmology, IRB 00008855 Soci\u0026eacute;t\u0026eacute; Fran\u0026ccedil;aise d\u0026rsquo;Ophtalmologie IRB#1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods and Ethical Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll methods were performed in accordance with the relevant guidelines and regulations of the Ethics Committee of the French Society of Ophthalmology, IRB 00008855 Soci\u0026eacute;t\u0026eacute; Fran\u0026ccedil;aise d\u0026rsquo;Ophtalmologie IRB#1\u003c/p\u003e\n\u003cp\u003eResearch all methods were performed in accordance with the Declaration of Helsinki. An international review board approved the study (Ethics Committee of the French Society of Ophthalmology, IRB 00008855 Soci\u0026eacute;t\u0026eacute; Fran\u0026ccedil;aise d\u0026rsquo;Ophtalmologie IRB#1).\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 patient for the publication of this case report and any accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data supporting the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no link of interest concerning this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors received no specific funding for this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePR drafted the original version of the manuscript. PR, AR and TM collected, analyzed and interpreted the patient data. They are major contributors in writing the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEG participated in the patient\u0026apos;s therapeutic care.\u003c/p\u003e\n\u003cp\u003eLA participated in the electrophysiological analysis. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the patient for providing written informed consent for the publication of this case report.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eDisclosure: \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eRossi A, Di Maio M. Platinum-based chemotherapy in advanced non-small-cell lung cancer: optimal number of treatment cycles. Expert Review of Anticancer Therapy. 2016 June 2;16(6):653\u0026ndash;60. \u003c/li\u003e\n\u003cli\u003eSchmid KE, Kornek GV, Scheithauer W, Binder S. Update on Ocular Complications of Systemic Cancer Chemotherapy. Survey of Ophthalmology. 2006 Jan;51(1):19\u0026ndash;40. \u003c/li\u003e\n\u003cli\u003eOun R, Moussa YE, Wheate NJ. The side effects of platinum-based chemotherapy drugs: a review for chemists. Dalton Trans. 2018;47(19):6645\u0026ndash;53. \u003c/li\u003e\n\u003cli\u003eDulz S, Asselborn NH, Dieckmann KP, Matthies C, Wagner W, Weidmann J, et al. Retinal toxicity after cisplatin-based chemotherapy in patients with germ cell cancer. J Cancer Res Clin Oncol. 2017 July;143(7):1319\u0026ndash;25. \u003c/li\u003e\n\u003cli\u003eAzar I, Yazdanpanah O, Jang H, Austin A, Kim S, Chi J, et al. Comparison of Carboplatin With Cisplatin in Small Cell Lung Cancer in US Veterans. JAMA Netw Open. 2022 Oct 20;5(10):e2237699. \u003c/li\u003e\n\u003cli\u003eMaleki A, Lagrew M, Slaney E. Bilateral Optic Neuropathy Secondary to Intravenous Carboplatin Therapy. JOVR. 2024 Mar 10;19(1):133\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eShihadeh S, Patrick MM, Postma G, Trokthi B, Maitland C. Blinding Optic Neuropathy Associated With Carboplatin Therapy: A Case Report and Literature Review. Cureus [Internet]. 2024 Jan 26 [cited 2025 Aug 25]; Available from: https://www.cureus.com/articles/196393-blinding-optic-neuropathy-associated-with-carboplatin-therapy-a-case-report-and-literature-review\u003c/li\u003e\n\u003cli\u003eLewis P, Waqar S, Yiannakis D, Raman V. Unilateral Optic Disc Papilloedema following Administration of Carboplatin Chemotherapy for Ovarian Carcinoma. Case Rep Oncol. 2014 Jan 10;7(1):29\u0026ndash;32. \u003c/li\u003e\n\u003cli\u003eCancer-associated retinopathy: an autoimmune retinopathy. Univ Med. 2010 25;29(1):56\u0026ndash;64. \u003c/li\u003e\n\u003cli\u003eMohamed Q. Acute Optical Coherence Tomographic Findings in Cancer-Associated Retinopathy. Arch Ophthalmol. 2007 Aug 1;125(8):1132. \u003c/li\u003e\n\u003cli\u003eWei MM, Armbrust KR, Jeffrey BG, Sen HN. Cancer-Associated Retinopathy. In: Gupta V, Nguyen QD, LeHoang P, Agarwal A, editors. The Uveitis Atlas [Internet]. New Delhi: Springer India; 2020. p. 605\u0026ndash;18. Available from: https://doi.org/10.1007/978-81-322-2410-5_102\u003c/li\u003e\n\u003cli\u003eJung YD, Lee SB, Jung YW, Song JS, Woo IS. Epiphora following chemotherapy with pemetrexed in patients with advanced non-small cell lung cancer. Korean J Intern Med. 2017 Sept 1;32(5):923\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eFortes BH, Liou H, Dalvin LA. Ophthalmic adverse effects of immune checkpoint inhibitors: the Mayo Clinic experience. Br J Ophthalmol. 2021 Sept;105(9):1263\u0026ndash;71. \u003c/li\u003e\n\u003cli\u003eTogna GI, Togna AR, Franconi M, Caprino L. Cisplatin Triggers Platelet Activation. Thrombosis Research. 2000 Sept;99(5):503\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eChiang TK, White KM, Kurup SK, Yu M. Use of Visual Electrophysiology to Monitor Retinal and Optic Nerve Toxicity. Biomolecules. 2022 Sept 29;12(10):1390. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Carboplatin, chemotherapy, lung cancer, macular toxicity, case report","lastPublishedDoi":"10.21203/rs.3.rs-8541064/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8541064/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTo describe a case of carboplatin-induced macular toxicity occurring during systemic treatment for metastatic non\u0026ndash;small cell lung cancer (NSCLC).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eRetrospective case report with a literature review.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA 48-year-old man developed bilateral vision loss one week after receiving a second cycle of chemoimmunotherapy consisting of carboplatin, pemetrexed, and pembrolizumab administered intravenously every four weeks. Clinical evaluation revealed rapidly progressive bilateral visual decline with a central scotoma. Multimodal imaging demonstrated foveal hyperautofluorescence and disruption of the foveal ellipsoid zone in both eyes. Electrophysiological testing showed foveal peak impairment on multifocal ERG, consistent with a toxic mechanism. Ocular and systemic findings were not suggestive of a paraneoplastic process. Following discontinuation of carboplatin, anatomical and functional abnormalities stabilized.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eCarboplatin-induced toxic maculopathy is rare and may result in visual acuity loss. Multimodal imaging indicates involvement of foveal photoreceptor. The reversibility of structural and functional changes after treatment cessation remains uncertain.\u003c/p\u003e","manuscriptTitle":"Toxic maculopathy associated with systemic Carboplatin therapy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-29 16:24:56","doi":"10.21203/rs.3.rs-8541064/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-14T11:41:23+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-10T15:07:50+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-24T05:58:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"325591169988954257822862777668668013306","date":"2026-03-17T09:56:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"35341894842052882173772976204399997805","date":"2026-03-13T10:45:15+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-25T04:28:50+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-23T01:04:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"271393112473754354972535527269591173508","date":"2026-02-16T00:22:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"164966175263833841245410577167010682628","date":"2026-02-15T18:48:59+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-01T10:26:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"331392581524194816997281185584781734612","date":"2026-01-28T15:13:48+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-26T17:35:13+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-22T10:42:33+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-20T10:53:52+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-13T19:21:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Oncology","date":"2026-01-13T19:15:52+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"611cd3a4-6404-4c83-a5c1-a3d5dab2fa9e","owner":[],"postedDate":"January 29th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-18T10:23:08+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-29 16:24:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8541064","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8541064","identity":"rs-8541064","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}