Mirvetuximab related corneal curvature fluctuations and consequent unstable refractive shift

Mirvetuximab related corneal curvature fluctuations and consequent unstable refractive shift | 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 correspondence Mirvetuximab related corneal curvature fluctuations and consequent unstable refractive shift Süleyman Çiftçi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8685207/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose : To describe the dynamic corneal changes following treatment with mirvetuximab soravtansine (MIRV) and to introduce characteristic imaging findings that help explain the refractive fluctuations observed during follow-up. Methods : A 56-year-old woman who underwent MIRV therapy presented with bilateral blurred vision. A comprehensive ophthalmologic evaluation, including slit-lamp examination, visual acuity testing, keratometry, corneal topography, and anterior segment optical coherence tomography, was performed. Findings were monitored during multiple follow-up visits. Results: Biomicroscopic examination revealed microcyst-like epithelial changes (MECs) in the mid-periphery. Corneal topography demonstrated irregular steepening corresponding to MEC distribution, while OCT imaging showed hyperreflective epithelial and stromal deposits. Over time, the deposits migrated toward the central and inferior corneas and then disappeared owing to the washout effect of the drug. The distribution and elimination processes produce unstable reshaping patterns and fluctuating refractive errors. At the last examination, visual acuity and aberration improved. No corneal haze or opacity was observed. Topical corticosteroid therapy did not provide a significant clinical benefit. Conclusion: MIRV-related corneal toxicity leads to unstable irregular astigmatism, increased higher-order aberrations, and fluctuating refractive status without corneal opacity. Recognizing this unique course is crucial for ophthalmologists to achieve accurate diagnosis, monitor visual outcomes, and provide appropriate patient counseling. Mirvetuximab soravtansine corneal toxicity refractive shift Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Key Message What is known? • The corneal lesions associated with antibody–drug conjugates (ADCs) have been described as microcysts. • Refractive changes and their fluctuation have generally been defined as simple defocus and regular astigmatism. This understanding is largely based on findings from standard keratometry or autorefractometry. Decreases in visual acuity have been simply attributed to these refractive changes. What is new? • OCT analysis suggests that these lesions represent antibody–drug conjugates rather than true microcysts, as microcysts typically exhibit hyporeflective features, whereas these lesions show hyperreflective characteristics. • Mirvetuximab soravtansine causes a dynamic, migratory accumulation of corneal deposits, leading to unstable corneal reshaping, irregular astigmatism, and fluctuating higher-order aberrations rather than simple defocus or regular astigmatism. • These changes are poorly captured by standard keratometry or autorefractometry. Serial corneal topography, supported by anterior segment OCT, can demonstrate the washout and clearance of previous corneal deposits, as well as the repetitive redistribution of new ADCs into the cornea. Introduction Antibody–drug conjugates (ADCs) are emerging treatments for gynecologic malignancies, and their use is expanding worldwide [ 1 ]. Corneal toxicity is a well-known ocular complication of these drugs, and the likelihood of encountering such complications in routine ophthalmological examinations is increasing day by day [ 2 , 3 , 4 ]. The molecular mechanisms suggested for the development of this complication have been previously discussed [ 5 , 6 ]. However, from the perspective of an ophthalmologist examining such patients, it is crucial to recognize the pattern of accumulation of these deposits in the cornea, their impact on refractive shift, and their characteristic roller-coaster shifting pattern. This is a case report of a 56-year-old woman with ovarian cancer who was currently undergoing Mirvetuximab soravtansine (MIRV) treatment. ADC-related corneal complications are described using imaging modalities, such as corneal topography and OCT. Unstable changes in the cornea are discussed in detail, and this aspect addresses a major gap in the literature that has not yet been studied. This study was approved by the Institutional Review Board of the Istanbul Beykent University. The tenets of the Declaration of Helsinki were followed in this study. Patient consent was obtained for the use of figures in this study. Case report The patient presented with blurred vision bilaterally. The patient was treated with mirvetuximab for ovarian cancer. The patient received a second dose of mirvetuximab when she was referred to the hospital. Slit-lamp examination, indirect ophthalmoscopy, Snellen visual acuity (VA), refractive error, keratometry readings, corneal topography, and corneal OCT were performed and repeated at each subsequent visit. On biomicroscopic examination, microcyst-like epithelial changes (MECs) in a circular pattern were detected in the midperiphery (Fig. 1 ). The corneal topography revealed a steepening in the areas occupied by the MECs (Fig. 2 ). OCT images of the anterior segment revealed hyperreflective deposits in the midperiphery of the epithelial layer and in the paracentral zone of the stroma. The epithelial layer was thickened in the midperiphery because of these deposits (Fig. 3 ). The best-corrected Snellen visual acuity was 0.9 in the right eye and 0.4 in the left eye. Intraocular pressure was 15/14 mmHg. The posterior segment examination results were normal. Topical dexamethasone drops were initiated according to the literature [ 3 , 4 ], and the patient was re-examined at four, twelve, twenty-three, twenty-eight, seventy-five days. Initial follow-up examinations revealed that the MECs were still present, but a more central area was occupied. During follow-up, she received three additional mirvetuximab treatments. Serial OCT images showed that the sections with significant refractile deposits at baseline demonstrated that these deposits decreased to negligible levels over the follow-up period. (Fig. 4 ). Autorefractometer readings changed and the corneal curvature reshaped at each visit; however, the reshaping patterns that developed toward the end were different from those observed earlier (Fig. 5 , Fig. 6 ). The irregular steepening areas gradually disappeared and transformed into a single, irregular steepening area that was more central and inferiorly located. Subsequently, all deposits were eliminated, and the cornea returned to its original curvature. The best-corrected refraction, as well as the total, low-order, and high-order aberrations, changed at each visit. A partial improvement was observed in all aberrations at the beginning of the follow-up period. All patients later showed complete deterioration at the mid-follow-up period and then completely returned to their original rate (Fig. 7 A, B). Topical dexamethasone drops did not appear effective. No haze or opacity was observed in the cornea during follow-up. Best-corrected visual acuity fell to 0.4/0.3 but then improved to 1.0/1.0 on the last visit. Discussion Although these lesions are called microcyst-like epithelial changes (MECs), they are also associated with antibody–drug conjugates (ADCs) [ 5 ]. In vivo confocal microscopy (IVCM) revealed that these lesions were hyperreflective [ 5 ]. Consistently, anterior OCT analysis in the present patient demonstrated similar hyperreflective characteristics, supporting IVCM observations. Although the epithelial layer is the primary concentration area of these hyperreflective deposits, it can also be observed throughout the stroma. Another finding on OCT was that although these lesions were defined as microcysts, microcysts typically have hyporeflective features. Rather than representing microcyst formation, the OCT analysis results suggested that these lesions were antibody–drug conjugates. With respect to follow-up, cross-sectional OCT analysis showed that the density of the deposits decreased in the screened section; however, this decrease did not represent true washout clearance of the deposits. Instead, it was associated with the redistribution and reaccumulation of deposits in another section. Topographic analysis was found to be more informative. A dynamic and unstable change in the anterior corneal curvature was observed during the follow-up period, while the posterior curvature remained relatively stable. The distribution of deposits seemed to follow a pattern during the early phase of follow-up; however, the washout and clearance of previous deposits from the cornea, along with the repetitive distribution of new ADCs into the cornea, continuously altered the corneal curvature. This repetitive distribution and irregular reaccumulation altered the refractive status of the cornea without any haze or media opacity. The absence of corneal opacity associated with MIRV has been confirmed in other studies [ 1 , 6 ]. Although refractive changes and their fluctuating nature were recognized, this change was defined as simple defocus and regular astigmatism [ 3 ]. Topography showed that ADCs affect the entire cornea and cause increased irregular astigmatism and higher-order aberrations, rather than simple defocus, resulting in unstable and irregular refractive shifts of the eye. Standard keratometry readings were not useful, because the measurements missed the steepest area. Therefore, best-corrected visual acuity decreased despite optimal correction of refractive error. Although topical steroid treatment has been reported to be useful, its beneficial effects were not confirmed in this patient [ 2 , 4 , 6 ]. The median time for resolution of MECs has been reported as 86.5 days [ 5 ]. The follow-up period for this patient was 75 days, and the deposits were completely cleared. In conclusion Increased irregular astigmatism and higher-order aberrations cause fluctuating and unstable visual impairments. The repetitive distribution and reaccumulation of ADCs deposits appeared to underlie these unstable refractive shifts. While OCT provides critical diagnostic information about ADCs distribution, serial topography can help understand what is happening in corneal curvatures. This is a new pathophysiological condition that affects corneal structure and refractive status. Recognizing this distinctive pattern is essential for ophthalmologists to ensure the accurate diagnosis, patient counseling, and appropriate management of ADC-related corneal toxicity. Declarations Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper. Acknowledgment The author (sc) wrote the main manuscript text, prepared all figures, collected the data, and conducted the patient examinations and follow-up visits. While preparing this work, the author used ChatGPT-3.5 and Grammarly to check punctuation, syntax, and the flow of the text. The manuscript was subsequently checked and edited using Paperpal Preflight. After using these tools, the author reviewed and revised the manuscript as needed and takes full responsibility for the content of the publication. There is no conflict to disclose. References Matulonis UA, Lorusso D, Oaknin A, et al. Efficacy and Safety of Mirvetuximab Soravtansine in Patients With Platinum-Resistant Ovarian Cancer With High Folate Receptor Alpha Expression: Results From the SORAYA Study. J Clin Oncol. 2023;41:2436–45. 10.1200/JCO.22 . Kunkler AL, Binkley EM, Mantopoulos D, et al. Known and novel ocular toxicities of biologics, targeted agents, and traditional chemotherapeutics. Graefe’s Archive Clin Experimental Ophthalmol. 2019;257(8):1771–81. 10.1007/s00417-019-04337-8 . Canestraro J, Hultcrantz M, Modi S, et al. Refractive Shifts and Changes in Corneal Curvature Associated With Antibody-Drug Conjugates. Cornea. 2022;41(6). 10.1097/ICO.0000000000002934 . Corbelli E, Miserocchi E, Marchese A, et al. Ocular Toxic Mirvetuximab Cornea. 2019;38(2). 10.1097/ICO.0000000000001805 . Farooq AV, Degli Esposti S, Popat R, et al. Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody–Drug Conjugate Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study. Ophthalmol Ther. 2020;9(4). 10.1007/s40123-020-00280-8 . Hendershot A, Slabaugh M, Riaz KM, et al. Strategies for prevention and management of ocular events occurring with mirvetuximab soravtansine. Gynecol Oncol Rep. 2023;47. 10.1016/j.gore.2023.101155 . 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-8685207","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"correspondence","associatedPublications":[],"authors":[{"id":582231344,"identity":"8c6902af-7d89-4d01-9c37-d05be171e97e","order_by":0,"name":"Süleyman Çiftçi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABNUlEQVRIie2RMWuDQBTHnz1oFo0dFaH5Cieu0s9yh3BZSmjJUuiQiKBLIKsO/Q5Ot9YgNIu060GWhEC3QkoXIR16Fh1Cla6F+hvu7vHuB/93B9DT8ydB83pXtgDYJQDndSfrUpRGQfYcMKsV8q00vQ4FKgXy35VRTP29dn010SM02JY3LxPdYHR/W8LlUJDB/u6nggUNHI17UyNHir/Am6kZs9yJCTimIIpftCgGDS2NI5oifRUA3tBUjENLJSAPUmlJJoNFR43PpIIUqTzTRzGOjlKZdSkgaIg0njdKRlODPSGpENyh4GIXmA98TWM5S7LAcqji1bNUZthJsfOTtmCRtzq88Xu6XOZwKD+rp2P2h+q6o+Hay97bgknO1JPyglSrAdD1k1WnPCn1rOtiT09Pzz/lCw3ibllm3ziRAAAAAElFTkSuQmCC","orcid":"","institution":"İstanbul Beykent University","correspondingAuthor":true,"prefix":"","firstName":"Süleyman","middleName":"","lastName":"Çiftçi","suffix":""}],"badges":[],"createdAt":"2026-01-24 08:54:39","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-8685207/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8685207/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101758319,"identity":"8a577573-0197-4b6f-9fd4-bb7975b9bb96","added_by":"auto","created_at":"2026-02-03 11:06:44","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1485133,"visible":true,"origin":"","legend":"\u003cp\u003eA shows the right eye, while B and C show the left eye. In the crescents and lunate frames, iris details appear slightly blurry, and microcyst-like epithelial changes are noticeable. Fluorescein staining under cobalt blue light revealed faint punctate epitheliopathy. The patient did not complain of dryness or redness in her eyes; instead, she reported a sudden worsening of both distance and near vision shortly after receiving MIRV treatment.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8685207/v1/62b7ae8a4dab4524fb8f89fa.png"},{"id":101757309,"identity":"d80a8cd3-2260-43c4-8f60-89b966e7361c","added_by":"auto","created_at":"2026-02-03 11:02:15","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1559016,"visible":true,"origin":"","legend":"\u003cp\u003eCorneal topography showed irregular steepening in the pattern of two face-to-face crescents in the midperiphery. The keratoscope showed irregular, distorted rings across the entire surface. The anterior elevation map showed an irregular, bean-like pattern of two face-to-face shapes, while the posterior elevation map showed inferior temporal elevation.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8685207/v1/0ae244d375b42307799671d1.png"},{"id":101757328,"identity":"8a3f891f-e963-47a8-9616-1862afbe5736","added_by":"auto","created_at":"2026-02-03 11:02:20","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1206248,"visible":true,"origin":"","legend":"\u003cp\u003eA cross-sectional infrared and color OCT image from the 3 o’clock position of the right eye and the 9 o’clock position of the left eye is shown. Although hyperreflective deposits are visible throughout the entire cornea, they appear more condensed in certain areas. The frames are marked on one image but correspond to the same anatomical regions in both eyes and in both the infrared and color images. In the epithelial layer, deposits accumulate in the midperiphery (green frame), while the epithelial layer in the red frame remains completely intact. In contrast, in the stromal layer, deposits accumulate in the paracentral region (blue frame). The more central the region, the deeper the accumulation observed. The limbus area, especially the nasal site, showed greater hyperreflectivity compared to other regions of the limbus.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8685207/v1/c3fe880309eed628c3e08909.png"},{"id":101758148,"identity":"09682171-4289-4248-abfc-3fd96f1dce58","added_by":"auto","created_at":"2026-02-03 11:06:00","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1025649,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of cross-sectional OCT images from the same location at the first and four weeks later examinations showed that the refractile deposits became less dense due to migration toward the inferior paracentral area of the cornea, but they still persisted.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8685207/v1/0b3c7c4b5dfd92423a790cf0.png"},{"id":101757091,"identity":"8b41c022-dbe1-46b9-a62a-5215b4f1bc43","added_by":"auto","created_at":"2026-02-03 11:01:35","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":2570543,"visible":true,"origin":"","legend":"\u003cp\u003eSerial tangential corneal topography revealed that the steepest area gradually shifted toward the central and inferior cornea over time, then completely disappeared.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-8685207/v1/c5085636a05ad0e44bf536cc.png"},{"id":101757281,"identity":"e224435a-aa5e-4060-af2d-bfc72c7afb73","added_by":"auto","created_at":"2026-02-03 11:02:12","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":621838,"visible":true,"origin":"","legend":"\u003cp\u003eThe patient’s autorefractometer values changed at each visit but fell short of reflecting the reshaping of the anterior corneal curvature.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-8685207/v1/212bd8db74d9747c63777d2f.png"},{"id":101757028,"identity":"58b32e1c-ff12-4da8-8188-070c6e5dccfd","added_by":"auto","created_at":"2026-02-03 11:01:23","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":1690321,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA\u003c/strong\u003e: Comparison of best corrected refraction, low-order and high-order aberrations from baseline to the final examination in the right eye. Green frames indicate the patient’s best-corrected refraction at each examination, while red frames show the total, low-order, and high-order aberrations for each visit. All aberrations and the best-corrected refraction worsened during treatment, but after clearance of the drug from the body following the first cycle, all aberrations improved, and the best-corrected refraction returned to the patient’s baseline status.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eB\u003c/strong\u003e: Comparison of best corrected refraction, low-order and high-order aberrations from baseline to the final examination in the left eye. Green frames indicate the patient’s best-corrected refraction at each examination, while red frames show the total, low-order, and high-order aberrations for each visit. All aberrations and the best-corrected refraction worsened during treatment, but after clearance of the drug from the body following the first cycle, all aberrations improved, and the best-corrected refraction returned to the patient’s baseline status.\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-8685207/v1/ca04474b7ebe4425ed727886.png"},{"id":101759557,"identity":"93f0ef8e-dfd2-47d9-927c-c82e3039803e","added_by":"auto","created_at":"2026-02-03 11:12:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":11809963,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8685207/v1/229f4825-b888-4f22-9bd1-933440e96ea2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Mirvetuximab related corneal curvature fluctuations and consequent unstable refractive shift","fulltext":[{"header":"Key Message","content":"\u003cp\u003e\u003cstrong\u003eWhat is known?\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e• \u0026nbsp;The corneal lesions associated with antibody–drug conjugates (ADCs) have been described as microcysts.\u003c/p\u003e\n\u003cp\u003e• \u0026nbsp;Refractive changes and their fluctuation have generally been defined as simple defocus and regular astigmatism. This understanding is largely based on findings from standard keratometry or autorefractometry. Decreases in visual acuity have been simply attributed to these refractive changes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWhat is new?\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e• \u0026nbsp;OCT analysis suggests that these lesions represent antibody–drug conjugates rather than true microcysts, as microcysts typically exhibit hyporeflective features, whereas these lesions show hyperreflective characteristics.\u003c/p\u003e\n\u003cp\u003e• \u0026nbsp; Mirvetuximab soravtansine causes a dynamic, migratory accumulation of corneal deposits, leading to unstable corneal reshaping, irregular astigmatism, and fluctuating higher-order aberrations rather than simple defocus or regular astigmatism.\u003c/p\u003e\n\u003cp\u003e• \u0026nbsp;These changes are poorly captured by standard keratometry or autorefractometry. Serial corneal topography, supported by anterior segment OCT, can demonstrate the washout and clearance of previous corneal deposits, as well as the repetitive redistribution of new ADCs into the cornea.\u0026nbsp;\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eAntibody\u0026ndash;drug conjugates (ADCs) are emerging treatments for gynecologic malignancies, and their use is expanding worldwide [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Corneal toxicity is a well-known ocular complication of these drugs, and the likelihood of encountering such complications in routine ophthalmological examinations is increasing day by day [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The molecular mechanisms suggested for the development of this complication have been previously discussed [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, from the perspective of an ophthalmologist examining such patients, it is crucial to recognize the pattern of accumulation of these deposits in the cornea, their impact on refractive shift, and their characteristic roller-coaster shifting pattern. This is a case report of a 56-year-old woman with ovarian cancer who was currently undergoing Mirvetuximab soravtansine (MIRV) treatment. ADC-related corneal complications are described using imaging modalities, such as corneal topography and OCT. Unstable changes in the cornea are discussed in detail, and this aspect addresses a major gap in the literature that has not yet been studied.\u003c/p\u003e \u003cp\u003eThis study was approved by the Institutional Review Board of the Istanbul Beykent University. The tenets of the Declaration of Helsinki were followed in this study. Patient consent was obtained for the use of figures in this study.\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003eThe patient presented with blurred vision bilaterally. The patient was treated with mirvetuximab for ovarian cancer. The patient received a second dose of mirvetuximab when she was referred to the hospital. Slit-lamp examination, indirect ophthalmoscopy, Snellen visual acuity (VA), refractive error, keratometry readings, corneal topography, and corneal OCT were performed and repeated at each subsequent visit. On biomicroscopic examination, microcyst-like epithelial changes (MECs) in a circular pattern were detected in the midperiphery (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The corneal topography revealed a steepening in the areas occupied by the MECs (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). OCT images of the anterior segment revealed hyperreflective deposits in the midperiphery of the epithelial layer and in the paracentral zone of the stroma. The epithelial layer was thickened in the midperiphery because of these deposits (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The best-corrected Snellen visual acuity was 0.9 in the right eye and 0.4 in the left eye. Intraocular pressure was 15/14 mmHg. The posterior segment examination results were normal. Topical dexamethasone drops were initiated according to the literature [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], and the patient was re-examined at four, twelve, twenty-three, twenty-eight, seventy-five days. Initial follow-up examinations revealed that the MECs were still present, but a more central area was occupied. During follow-up, she received three additional mirvetuximab treatments. Serial OCT images showed that the sections with significant refractile deposits at baseline demonstrated that these deposits decreased to negligible levels over the follow-up period. (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Autorefractometer readings changed and the corneal curvature reshaped at each visit; however, the reshaping patterns that developed toward the end were different from those observed earlier (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). The irregular steepening areas gradually disappeared and transformed into a single, irregular steepening area that was more central and inferiorly located. Subsequently, all deposits were eliminated, and the cornea returned to its original curvature. The best-corrected refraction, as well as the total, low-order, and high-order aberrations, changed at each visit. A partial improvement was observed in all aberrations at the beginning of the follow-up period. All patients later showed complete deterioration at the mid-follow-up period and then completely returned to their original rate (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e7\u003c/span\u003eA, B). Topical dexamethasone drops did not appear effective. No haze or opacity was observed in the cornea during follow-up. Best-corrected visual acuity fell to 0.4/0.3 but then improved to 1.0/1.0 on the last visit.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAlthough these lesions are called microcyst-like epithelial changes (MECs), they are also associated with antibody\u0026ndash;drug conjugates (ADCs) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In vivo confocal microscopy (IVCM) revealed that these lesions were hyperreflective [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Consistently, anterior OCT analysis in the present patient demonstrated similar hyperreflective characteristics, supporting IVCM observations. Although the epithelial layer is the primary concentration area of these hyperreflective deposits, it can also be observed throughout the stroma. Another finding on OCT was that although these lesions were defined as microcysts, microcysts typically have hyporeflective features. Rather than representing microcyst formation, the OCT analysis results suggested that these lesions were antibody\u0026ndash;drug conjugates. With respect to follow-up, cross-sectional OCT analysis showed that the density of the deposits decreased in the screened section; however, this decrease did not represent true washout clearance of the deposits. Instead, it was associated with the redistribution and reaccumulation of deposits in another section. Topographic analysis was found to be more informative. A dynamic and unstable change in the anterior corneal curvature was observed during the follow-up period, while the posterior curvature remained relatively stable. The distribution of deposits seemed to follow a pattern during the early phase of follow-up; however, the washout and clearance of previous deposits from the cornea, along with the repetitive distribution of new ADCs into the cornea, continuously altered the corneal curvature. This repetitive distribution and irregular reaccumulation altered the refractive status of the cornea without any haze or media opacity. The absence of corneal opacity associated with MIRV has been confirmed in other studies [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Although refractive changes and their fluctuating nature were recognized, this change was defined as simple defocus and regular astigmatism [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Topography showed that ADCs affect the entire cornea and cause increased irregular astigmatism and higher-order aberrations, rather than simple defocus, resulting in unstable and irregular refractive shifts of the eye. Standard keratometry readings were not useful, because the measurements missed the steepest area. Therefore, best-corrected visual acuity decreased despite optimal correction of refractive error. Although topical steroid treatment has been reported to be useful, its beneficial effects were not confirmed in this patient [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The median time for resolution of MECs has been reported as 86.5 days [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The follow-up period for this patient was 75 days, and the deposits were completely cleared.\u003c/p\u003e"},{"header":"In conclusion","content":"\u003cp\u003eIncreased irregular astigmatism and higher-order aberrations cause fluctuating and unstable visual impairments. The repetitive distribution and reaccumulation of ADCs deposits appeared to underlie these unstable refractive shifts. While OCT provides critical diagnostic information about ADCs distribution, serial topography can help understand what is happening in corneal curvatures. This is a new pathophysiological condition that affects corneal structure and refractive status. Recognizing this distinctive pattern is essential for ophthalmologists to ensure the accurate diagnosis, patient counseling, and appropriate management of ADC-related corneal toxicity.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eDeclaration of Competing Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author (sc) wrote the main manuscript text, prepared all figures, collected the data, and conducted the patient examinations and follow-up visits. While preparing this work, the author used ChatGPT-3.5 and Grammarly to check punctuation, syntax, and the flow of the text. The manuscript was subsequently checked and edited using Paperpal Preflight. After using these tools, the author reviewed and revised the manuscript as needed and takes full responsibility for the content of the publication.\u003c/p\u003e\n\u003cp\u003eThere is no conflict to disclose.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMatulonis UA, Lorusso D, Oaknin A, et al. Efficacy and Safety of Mirvetuximab Soravtansine in Patients With Platinum-Resistant Ovarian Cancer With High Folate Receptor Alpha Expression: Results From the SORAYA Study. J Clin Oncol. 2023;41:2436\u0026ndash;45. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1200/JCO.22\u003c/span\u003e\u003cspan address=\"10.1200/JCO.22\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKunkler AL, Binkley EM, Mantopoulos D, et al. Known and novel ocular toxicities of biologics, targeted agents, and traditional chemotherapeutics. Graefe\u0026rsquo;s Archive Clin Experimental Ophthalmol. 2019;257(8):1771\u0026ndash;81. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00417-019-04337-8\u003c/span\u003e\u003cspan address=\"10.1007/s00417-019-04337-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCanestraro J, Hultcrantz M, Modi S, et al. Refractive Shifts and Changes in Corneal Curvature Associated With Antibody-Drug Conjugates. Cornea. 2022;41(6). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/ICO.0000000000002934\u003c/span\u003e\u003cspan address=\"10.1097/ICO.0000000000002934\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCorbelli E, Miserocchi E, Marchese A, et al. Ocular Toxic Mirvetuximab Cornea. 2019;38(2). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/ICO.0000000000001805\u003c/span\u003e\u003cspan address=\"10.1097/ICO.0000000000001805\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFarooq AV, Degli Esposti S, Popat R, et al. Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody\u0026ndash;Drug Conjugate Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study. Ophthalmol Ther. 2020;9(4). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s40123-020-00280-8\u003c/span\u003e\u003cspan address=\"10.1007/s40123-020-00280-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHendershot A, Slabaugh M, Riaz KM, et al. Strategies for prevention and management of ocular events occurring with mirvetuximab soravtansine. Gynecol Oncol Rep. 2023;47. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.gore.2023.101155\u003c/span\u003e\u003cspan address=\"10.1016/j.gore.2023.101155\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Mirvetuximab soravtansine, corneal toxicity, refractive shift","lastPublishedDoi":"10.21203/rs.3.rs-8685207/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8685207/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e: To describe the dynamic corneal changes following treatment with mirvetuximab soravtansine (MIRV) and to introduce characteristic imaging findings that help explain the refractive fluctuations observed during follow-up.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: A 56-year-old woman who underwent MIRV therapy presented with bilateral blurred vision. A comprehensive ophthalmologic evaluation, including slit-lamp examination, visual acuity testing, keratometry, corneal topography, and anterior segment optical coherence tomography, was performed. Findings were monitored during multiple follow-up visits.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eBiomicroscopic examination revealed microcyst-like epithelial changes (MECs) in the mid-periphery. Corneal topography demonstrated irregular steepening corresponding to MEC distribution, while OCT imaging showed hyperreflective epithelial and stromal deposits. Over time, the deposits migrated toward the central and inferior corneas and then disappeared owing to the washout effect of the drug. The distribution and elimination processes produce unstable reshaping patterns and fluctuating refractive errors. At the last examination, visual acuity and aberration improved. No corneal haze or opacity was observed. Topical corticosteroid therapy did not provide a significant clinical benefit.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eMIRV-related corneal toxicity leads to unstable irregular astigmatism, increased higher-order aberrations, and fluctuating refractive status without corneal opacity. Recognizing this unique course is crucial for ophthalmologists to achieve accurate diagnosis, monitor visual outcomes, and provide appropriate patient counseling.\u003c/p\u003e","manuscriptTitle":"Mirvetuximab related corneal curvature fluctuations and consequent unstable refractive shift","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-30 08:57:49","doi":"10.21203/rs.3.rs-8685207/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2a77dbdf-a8f4-4d04-a820-ab31dffed202","owner":[],"postedDate":"January 30th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-30T08:57:49+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-30 08:57:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8685207","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8685207","identity":"rs-8685207","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}