A rare case of infiltrative optic neuropathy caused by vitreoretinal lymphoma with intraretinal and subretinal pigmented epithelial hyperreflective deposits prior to the disease onset

A rare case of infiltrative optic neuropathy caused by vitreoretinal lymphoma with intraretinal and subretinal pigmented epithelial hyperreflective deposits prior to the disease onset | 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 A rare case of infiltrative optic neuropathy caused by vitreoretinal lymphoma with intraretinal and subretinal pigmented epithelial hyperreflective deposits prior to the disease onset Takako Kuji, Shimpei Komoto, Kazuichi Maruyama, Satoko Fujimoto, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4244258/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 Background To describe a rare case of infiltrative optic neuropathy caused by vitreoretinal lymphoma (VRL) with intraretinal and subretinal pigmented epithelial (RPE) hyperreflective deposits before the disease onset. Case presentation: We presented an 87-year-old Japanese female. At 5 months before onset, she noticed a decline of her right visual acuity, and she visited ophthalmology clinic because her visual acuity was progressively deteriorated to counting finger. In clinic, uveitis complicated with vitreous opacification (VO) was revealed, and subcapsular triamcinolone acetonide was injected for treatment. Although her visual acuity and VO were improved after treatment, she was referred to Osaka University Hospital for detailed examination. Her right visual acuity was 20/50. Intraocular inflammation and VO were not detected. There were yellowish-white deposits likes hard drusen in her right macula, and optical coherence tomography (OCT) showed intraretinal and sub-RPE hyperreflective deposits in the same area. One month later, she visited to our hospital with acute visual exacerbation. Her right visual acuity was hand motion. Optic disc swelling with disc hemorrhage was shown in the right eye. There was neither VO nor intraocular inflammation at this time, and a magnetic resonance imaging (MRI) of the head without enhancement did not show hyperintensity and swelling of the optic nerve as well as intracranial lesions. One week later, VO occurred and we performed 25-gauge vitrectomy for vitreous collection. Finally, after consideration of all the clinical examinations, a diagnosis was made of infiltrative optic nerve neuropathy with vitreoretinal B-cell lymphoma. Intraocular injection of methotrexate was administered a total of 6 times. At the time of the last visit (6 months after surgery), VO and optic disc swelling had disappeared. Careful observation was continued, but no recurrent findings including MRI was observed, and visual acuity in the right eye improved to 20/50. Conclusions Although there were reports on VRL advanced from intraretinal or sub-RPE hyperreflective deposits, there have been no studies that these OCT findings has progressed to infiltrative optic nerve neuropathy with VRL. When differentiating optic neuropathy, OCT may assist in the diagnosis by evaluating intraretinal and sub-RPE findings. Infiltrative optic neuropathy vitreoretinal lymphoma optical coherence tomography hyperreflective deposits Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background Vitreoretinal lymphoma (VRL) is recognized as a lymphocytic malignancy marked by the involvement of the uvea, retina, vitreous cavity, and optic nerve. The occurrence of infiltrative optic neuropathy due to lymphoma is infrequent, with estimates suggesting it constitutes approximately 5% of primary central nervous system (CNS) lymphomas 1 . Infiltrative optic neuropathy attributable to lymphoma, specifically optic nerve lymphoma, is categorized into four distinct types: solitary optic nerve lesions, optic nerve lesions with concurrent CNS disease, optic nerve lesions with systemic disease, and optic nerve lesions associated with VRL 1 . Among them, optic nerve lymphoma stemming from VRL is considered rare. Notably, in prior case reports concerning primary VRL, the majority already exhibit concurrent CNS lesions at the onset of infiltrative optic neuropathy 2 . Recent reports have highlighted that intraretinal and subretinal pigment epithelial (RPE) hyperreflective deposits, as identified through optical coherence tomography (OCT), may serve as early indicators of VRL 3 , 4 . While there are accounts of VRL progressing from such OCT findings, no studies have yet demonstrated progression to infiltrative optic nerve neuropathy in the context of VRL 3 . In present report, we detail a unique case of infiltrative optic neuropathy instigated by VRL, characterized by pre-onset intraretinal and sub-RPE hyperreflective deposits, a phenomenon hitherto unreported. Case presentation We presented an 87-year-old Japanese female, who had hypertension, hyperlipidemia, and osteoporosis as her past medical history. At 5 months before onset, she noticed a decline of her right visual acuity. After that, she visited ophthalmology clinic because her visual acuity was progressively deteriorated to counting finger. In clinic, uveitis complicated with vitreous opacification (VO) was revealed, and subcapsular triamcinolone acetonide was injected for treatment. Although her visual acuity and VO were improved after treatment, she was referred to Osaka University Hospital for detailed examination. Her right visual acuity was 20/50 and left visual acuity was 20/30. Intraocular inflammation and VO were not detected. There were yellowish-white deposits likes hard drusen in her right macula, and OCT showed intraretinal and sub-RPE hyperreflective deposits in the same area. (Fig. 1 A, B) However, there were no other abnormal findings through other ophthalmologic examination. Her left eye had no abnormal findings. We decided to observe in our hospital as uveitis of undetermined causes at this time. One month later, she visited to our hospital with acute visual exacerbation. Her right visual acuity was hand motion and left visual acuity was 20/30. Intraocular pressure was 18 mmHg in the right eye, and 17 mmHg in the left eye. She had a right afferent pupillary defect. Goldmann visual field perimetry was full in the left eye, but a large dense central scotoma was present in the right eye. (Fig. 2 A, B) Slit lamp examination was normal in the left eye, but optic disc swelling with disc hemorrhage was revealed in the right eye. Yellowish-white deposits likes hard drusen in her right macula was not changed before 1 month. (Fig. 2 C) Any intraocular inflammation and VO were not detected in both eyes. OCT showed prominent disc swelling with intraretinal and subretinal fluid. (Fig. 2 D) Her left eye was normal in the above ophthalmic imaging examination. (Fig. 2 E, F) We speculated the possibility of infiltrative optic neuropathy, because she had the previous medical history with VO complicated by unknown uveitis. However, a magnetic resonance imaging (MRI) of the head without enhancement did not show hyperintensity and swelling of the optic nerve as well as intracranial lesions. (Fig. 3 A, B) In addition, there was neither VO nor intraocular inflammation at this time. We considered that retinal biopsy for macular or papillary lesions were highly invasive for visual function, so decided to hospitalize the patient for steroid pulse treatment for prominent disc swelling at first. One week after hospitalization, VO occurred and we speculated that the intraretinal and sub-RPE hyperreflective deposits progressed to infiltrative optic nerve neuropathy with VRL. Therefore, we decided to perform 25-gauge microincision vitrectomy for vitreous collection in an emergency. Vitreous specimens were processed for cytology, flow cytometry, and gene rearrangement with the Registration Examination and Analysis Description (READ) system 5 . A histological examination indicated a lot of atypical cells with large nuclear/cytoplasm ratios suspected malignant lymphoma. (Fig. 4 A) Findings from the flow cytometry analysis revealed the infiltration of cells positive for CD45, CD19, and CD20, but not CD10 and CD22. Furthermore, the surface immunoglobulin cytochemical analysis revealed monotypic light chain expression restricted kappa chain. (Fig. 4 B) The results of a gene rearrangement analysis were positive for the immunoglobulin heavy locus. Finally, after consideration of all the clinical examinations, a diagnosis was made of infiltrative optic nerve neuropathy with vitreoretinal B-cell lymphoma. Therefore, we decided to treat the patient with the intraocular injection of methotrexate. Intraocular injection of methotrexate was administered a total of 6 times at intervals of about 2 weeks due to repeated corneal epithelial keratopathy. One month after operation, optic disc swelling and subretinal fluid were markedly improved. (Fig. 5 A, B) At the time of the last visit (6 months after surgery), VO and optic disc swelling had disappeared. In OCT image, intraretinal and sub-RPE deposits were remaining. (Fig. 5 C, D) Careful observation was continued, but no recurrent findings including MRI was observed, and visual acuity in the right eye at the last visit improved to 20/50. Discussion and Conclusions In the complex landscape of diagnosing optic neuropathy, the rare entity of infiltrative optic neuropathy associated with VRL poses significant challenges. This difficulty is accentuated in cases where the pathological manifestation is confined to the ocular structure, devoid of VO. Our case highlights an instance where the onset of VO, albeit fortuitously post-disease onset, facilitated a vitreous biopsy. This critical intervention enabled the early identification of infiltrative optic neuropathy driven by vitreoretinal B-cell lymphoma. The occurrence of VO not only served as a pivotal diagnostic marker but also underscored the imperative for ophthalmologists to maintain a high level of vigilance for the subtle signs indicating of VRL's early stages. OCT emerges as a cornerstone in the nuanced diagnosis of optic neuropathy, offering a window to detect early manifestations of VRL. Reports in the literature have elucidated that the appearance of intraretinal and sub-RPE hyperreflective signals as preliminary indicators of the disease, potentially denoting an uptick in disease activity 6 . However, the specificity of these signals warrants careful consideration, given their presence in other retinal conditions such as diabetic retinopathy and age-related macular degeneration 7 , 8 . This necessitates a discerning approach to differentiate these conditions accurately. Moreover, the presence of hyperreflective deposits across various retinal layers, as seen in cases of CNS malignant lymphoma, accentuates their potential as biomarkers for early VRL detection 4 . In the presented case, the precursory detection of hyperreflective deposits within the intraretinal and sub-RPE layers, against a background of a medical history devoid of diabetes but inclusive of VO from unclassified uveitis, was instrumental in guiding the provisional diagnosis towards infiltrative optic neuropathy. The absence of VO presents a diagnostic challenge, as the yield for malignancy through cytological examination significantly diminishes from 47.1% in the presence of VO to merely 10.0% without VO 9 . Moreover, considering the high risk associated with retinal biopsies of the optic disc or macula, particularly in terms of visual function, such procedures are deemed highly invasive. Therefore, present case to delay surgical intervention until the manifestation of VO was strategically prudent. This approach aimed to enhance the accuracy of the malignancy diagnosis while concurrently mitigating the risk to the patient’s visual function. In discussing MRI findings relevant to infiltrative optic neuropathy, it is important to note that even without contrast enhancement, MRI can reveal thickening of the optic nerve, a hallmark of this condition 10 . Lymphoma infiltration and optic neuritis present similarly on MRI, showing low to iso-intensity on T1 and high intensity on T2-weighted images 10 . Contrast-enhanced MRIs often show significant enhancement in optic nerve lymphoma cases, with literature noting up to 88% of cases displaying this feature 11 , 12 . From the above, it is considered that the diagnosis can be made by MRI regardless of contrast enhancement if optic nerve lymphoma is typical case. However, MRI images showed no abnormal findings in our case. As a reason for that, we speculate that the optic nerve lesion is probably still localized in the optic disc, because of very early stage of infiltration from VRL. Moreover, past reports described above described that not all cases have abnormal findings on MRI 12 . Therefore, it is necessary to make a comprehensive judgment based on the results of various examination. In conclusion, our exploration into the progression of intraretinal and sub-RPE lesions to infiltrative optic nerve neuropathy via OCT substantiates the lesions as forerunners of optic nerve infiltration by VRL. Despite significant therapeutic advancements, the persistence of intraretinal and sub-RPE deposits post-treatment underscores the necessity for continuous monitoring. OCT's indispensable role in differentiating optic neuropathy and the potential CNS spread from VRL necessitate vigilant observation and frequent evaluations to preemptively address any disease advancement, thereby emphasizing the importance of an integrated and proactive diagnostic and management strategy in suspected VRL cases. Abbreviations VRL: vitreoretinal lymphoma, CNS: central nervous system, RPE: retinal pigment epithelial, OCT: optical coherence tomography, VO: vitreous opacification, MRI: magnetic resonance imaging Declarations Ethics approval and consent to participate Patient was provided informed consent using opt-out approach instead of informed written consent. This report does not contain any personal information that could lead to the identification of the patient. The Institutional Review Board of the Osaka University Medical School approved the research protocol, and the procedures conformed to the tenets of the Declaration of Helsinki. Consent for publication Patient was provided informed consent using opt-out approach instead of informed written consent. This report does not contain any personal information that could lead to the identification of the patient. Availability of data and materials All data generated or analyzed during this study are included in this published article. Competing Interest The authors declare that there are no conflicts of interest regarding the publication of this paper. Funding No funding or grant support. Authors’ contributions T.K. and S.K. participated in drafting the manuscript and collection, analysis, and interpretation of the data. S.K. and K.M. participated in diagnosis and treatment of the patient, drafting the manuscript, and revising the manuscript. S.F., T.F., Y.K., H.S., T.M. and K.N. critically reviewed the manuscript and reviewed the literature. All authors consented to their names being published in this report and insist on the intellectual honesty and validity of the data provided. All authors read and approved the final version of the paper. Acknowledgments Not applicable. Author’s information (optional) Not applicable. References Kim JL, Mendoza PR, Rashid A, Hayek B, Grossniklaus HE. Optic nerve lymphoma: report of two cases and review of the literature. Surv Ophthalmol. 2015 Mar-Apr;60(2):153-65. Doi: 10.1016/j.survophthal.2014.11.004. Epub 2014 Dec 18. PMID: 25595061; PMCID: PMC4334739. Gill MK, Jampol LM. Variations in the presentation of primary intraocular lymphoma: case reports and a review. Surv Ophthalmol. 2001 May-Jun;45(6):463-71. Doi: 10.1016/s0039-6257(01)00217-x. PMID: 11425352. Liu, T.Y.A., Ibrahim, M., Bittencourt, M. et al. Retinal optical coherence tomography manifestations of intraocular lymphoma. J Ophthal Inflamm Infect 2 , 215–218 (2012). https://doi.org/10.1007/s12348-012-0072-z Hassan, M., Halim, M.S., Afridi, R. et al. Evaluating optical coherence tomography (OCT) findings as potential biomarkers in central nervous system (CNS) lymphoma with or without ocular involvement. Int J Retin Vitr 7 , 70 (2021). https://doi.org/10.1186/s40942-021-00345-1 Otomo T, Fuse N, Ishizawa K, Seimiya M, Shimura M, Ryo Ichinohazama. Japanese case of follicular lymphoma of ocular adnexa diagnosed by clinicopathologic, immunohistochemical, and molecular genetic techniques. Clin Ophthalmol . 2010;4:1397-1402 https://doi.org/10.2147/OPTH.S15219) Jang, H.S., Sepah, Y.J., Sophie, R. et al. Longitudinal spectral domain optical coherence tomography changes in eyes with intraocular lymphoma. J Ophthal Inflamm Infect 3 , 59 (2013). https://doi.org/10.1186/1869-5760-3-59 Folgar FA, Chow JH, Farsiu S, Wong WT, Schuman SG, O’Connell RV, Winter KP, Chew EY, Hwang TS, Srivastava SK, Harrington MW, Clemons TE, Toth CA. Spatial correlation between hyperpigmentary changes on color fundus photography and hyperreflective foci on SDOCT in intermediate AMD. Invest Ophthalmol Vis Sci. 2012 Jul 9;53(8):4626-33. Doi: 10.1167/iovs.12-9813. PMID: 22589439. Bolz M, Schmidt-Erfurth U, Deak G, Mylonas G, Kriechbaum K, Scholda C; Diabetic Retinopathy Research Group Vienna. Optical coherence tomographic hyperreflective foci: a morphologic sign of lipid extravasation in diabetic macular edema. Ophthalmology. 2009 May;116(5):914-20. Doi: 10.1016/j.ophtha.2008.12.039. PMID: 19410950. Kimura K, Usui Y, Goto H; Japanese Intraocular Lymphoma Study Group. Clinical features and diagnostic significance of the intraocular fluid of 217 patients with intraocular lymphoma. Jpn J Ophthalmol. 2012 Jul;56(4):383-9. Doi: 10.1007/s10384-012-0150-7. Epub 2012 Jun 5. PMID: 22661396. Yo Han Ra, Sun Young Park, Soo Ah Im, Jee Young Kim, Nak Gyun Chung, and Bin Cho; Enhancement of Optic Nerve in Leukemic Patients: Leukemic Infiltration of Optic Nerve versus Optic Neuritis. Investig Magn Reson Imaging. 2016 Sep;20(3):167-174. https://doi.org/10.13104/imri.2016.20.3.167 Ahle G, Touitou V, Cassoux N, et al. Optic Nerve Infiltration in Primary Central Nervous System Lymphoma. JAMA Neurol. 2017;74(11):1368–1373. Doi:10.1001/jamaneurol.2017.2545 Yang M, Zhao J, Song H, Wei S, Zhou H, Xu Q. Orbital Magnetic Resonance Imaging May Contribute to the Diagnosis of Optic Nerve Lymphoma. Front Neurol. 2020 Apr 28;11:301. Doi: 10.3389/fneur.2020.00301. PMID: 32411078; PMCID: PMC7198801. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-4244258","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":290351256,"identity":"091c6db5-e08c-4e4e-8f06-9c67ae89de3d","order_by":0,"name":"Takako Kuji","email":"","orcid":"","institution":"Osaka University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Takako","middleName":"","lastName":"Kuji","suffix":""},{"id":290351257,"identity":"26c9d3b8-6449-44bd-91eb-2e2d06b9343f","order_by":1,"name":"Shimpei Komoto","email":"","orcid":"","institution":"Osaka University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Shimpei","middleName":"","lastName":"Komoto","suffix":""},{"id":290351258,"identity":"619537f7-14e0-4775-8e03-a83d767deff8","order_by":2,"name":"Kazuichi Maruyama","email":"data:image/png;base64,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","orcid":"","institution":"Osaka University Graduate School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Kazuichi","middleName":"","lastName":"Maruyama","suffix":""},{"id":290351259,"identity":"fae0a6e9-6065-4670-a890-fd069024a289","order_by":3,"name":"Satoko Fujimoto","email":"","orcid":"","institution":"Osaka University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Satoko","middleName":"","lastName":"Fujimoto","suffix":""},{"id":290351260,"identity":"f2cc5a94-ea95-4aab-bfa2-d4bfee20284c","order_by":4,"name":"Takahiro Fujino","email":"","orcid":"","institution":"Osaka University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Takahiro","middleName":"","lastName":"Fujino","suffix":""},{"id":290351261,"identity":"5f83dab1-84f6-454a-a48b-51e1b2c77302","order_by":5,"name":"Yoshiyuki Kitaguchi","email":"","orcid":"","institution":"Osaka University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yoshiyuki","middleName":"","lastName":"Kitaguchi","suffix":""},{"id":290351262,"identity":"9a89997a-a01b-4264-80ce-88241477d668","order_by":6,"name":"Hiroshi Shimojo","email":"","orcid":"","institution":"Osaka University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hiroshi","middleName":"","lastName":"Shimojo","suffix":""},{"id":290351263,"identity":"58b07df8-8e26-4809-9704-5ef725a21477","order_by":7,"name":"Takeshi Morimoto","email":"","orcid":"","institution":"Osaka University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Takeshi","middleName":"","lastName":"Morimoto","suffix":""},{"id":290351264,"identity":"9397c752-e2a7-4d6c-888c-123342fd33d5","order_by":8,"name":"Kohji Nishida","email":"","orcid":"","institution":"Osaka University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kohji","middleName":"","lastName":"Nishida","suffix":""}],"badges":[],"createdAt":"2024-04-10 00:14:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4244258/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4244258/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":54999523,"identity":"dd13b32a-72c2-40f1-a7bf-5a93e48398de","added_by":"auto","created_at":"2024-04-19 18:30:00","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":482390,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eOphthalmological appearance and images at first visit to our hospital\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA) \u003c/strong\u003eA fundus image shows yellowish-white deposits likes hard drusen in her right macula. (black arrow)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eB) \u003c/strong\u003eAn OCT image shows intraretinal and sub-RPE hyperreflective deposits. (white arrows)\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4244258/v1/ecabe04ff9a9a47a4c284e5a.png"},{"id":55004340,"identity":"8e4503c4-3266-4c17-aa9d-40edd9cccc26","added_by":"auto","created_at":"2024-04-19 18:46:01","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1927314,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eOphthalmological appearance and images at the disease onset\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA) \u003c/strong\u003eGoldmann visual field perimetry is full in the left eye.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eB) \u003c/strong\u003eGoldmann visual field perimetry finds that a large dense central scotoma within a 30-degree range and arcuate peripheral vision remains only on the nasal side of the right eye.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eC) \u003c/strong\u003eA fundus image shows optic disc swelling with disc hemorrhage in the right eye. (white arrow) Yellowish-white deposits likes hard drusen in her right macula was not changed before 1 month. (black arrow)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eD) \u003c/strong\u003eAn OCT image shows prominent disc swelling with intraretinal and subretinal fluid in right eye.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eE) \u003c/strong\u003eA fundus image shows no abnormal findings in her left eye.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eF) \u003c/strong\u003eAn OCT image shows no abnormal findings in her left eye.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4244258/v1/478cd787809b3388797ba212.png"},{"id":55001523,"identity":"de782ecc-4d44-4a14-9fc6-f4fc10976fc9","added_by":"auto","created_at":"2024-04-19 18:38:01","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":609146,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCranial MRI images at the disease onset\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA) \u003c/strong\u003eA T2-weighted non-enhancement MRI image of the head in coronal scanning shows no abnormal findings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eB) \u003c/strong\u003eA T2-weighted non-enhancement MRI image of the head in axial scanning shows no abnormal findings.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4244258/v1/ebbd7f964e2d2d5f12174f6a.png"},{"id":54999524,"identity":"ee473e2f-96d0-4afa-b92a-09db8fbbe92d","added_by":"auto","created_at":"2024-04-19 18:30:01","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":686770,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eResults or intraoperative histology and flow cytometry\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA) \u003c/strong\u003eA histological examination on hematoxylin and eosin-stained indicates a lot of atypical cells with large nuclear/cytoplasm ratios suspected malignant lymphoma.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eB) \u003c/strong\u003eFindings from the flow cytometry analysis shows that the infiltration of cells positive for CD45, CD19, and CD20, but not CD10 and CD22. Furthermore, the surface immunoglobulin cytochemical analysis revealed monotypic light chain expression restricted kappa chain.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-4244258/v1/700dff05b7997dcaa6d2cb7a.png"},{"id":54999528,"identity":"8259ef2e-a18c-4417-870c-3a41764e6730","added_by":"auto","created_at":"2024-04-19 18:30:01","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":807890,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eOphthalmological appearance and images after the start of treatment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA) \u003c/strong\u003eA fundus image at postoperative 1 month shows remarkable improvement of disc swelling and subretinal fluid. There are still residual disc hemorrhages.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eB) \u003c/strong\u003eAn OCT image at postoperative 1 month shows intraretinal and subretinal fluid are disappeared.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eC) \u003c/strong\u003eA fundus image at last visit (postoperative 6 month) shows completely remission of disc swelling, disc hemorrhage, and subretinal fluid.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eD) \u003c/strong\u003eAn OCT image at last visit (postoperative 6 month) shows stable findings without recurrence. Intraretinal and sub-RPE deposits are remaining. (white arrows)\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-4244258/v1/80d00c21eee1bf2ac6b7106c.png"},{"id":56233457,"identity":"bdeec075-16b3-47cf-87ef-754ce9b22c53","added_by":"auto","created_at":"2024-05-10 08:05:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5178973,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4244258/v1/3122ce3a-4ebe-4a94-a1b2-3bab70fd4d7d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A rare case of infiltrative optic neuropathy caused by vitreoretinal lymphoma with intraretinal and subretinal pigmented epithelial hyperreflective deposits prior to the disease onset","fulltext":[{"header":"Background","content":"\u003cp\u003eVitreoretinal lymphoma (VRL) is recognized as a lymphocytic malignancy marked by the involvement of the uvea, retina, vitreous cavity, and optic nerve. The occurrence of infiltrative optic neuropathy due to lymphoma is infrequent, with estimates suggesting it constitutes approximately 5% of primary central nervous system (CNS) lymphomas \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Infiltrative optic neuropathy attributable to lymphoma, specifically optic nerve lymphoma, is categorized into four distinct types: solitary optic nerve lesions, optic nerve lesions with concurrent CNS disease, optic nerve lesions with systemic disease, and optic nerve lesions associated with VRL \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Among them, optic nerve lymphoma stemming from VRL is considered rare. Notably, in prior case reports concerning primary VRL, the majority already exhibit concurrent CNS lesions at the onset of infiltrative optic neuropathy \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eRecent reports have highlighted that intraretinal and subretinal pigment epithelial (RPE) hyperreflective deposits, as identified through optical coherence tomography (OCT), may serve as early indicators of VRL \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. While there are accounts of VRL progressing from such OCT findings, no studies have yet demonstrated progression to infiltrative optic nerve neuropathy in the context of VRL \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. In present report, we detail a unique case of infiltrative optic neuropathy instigated by VRL, characterized by pre-onset intraretinal and sub-RPE hyperreflective deposits, a phenomenon hitherto unreported.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eWe presented an 87-year-old Japanese female, who had hypertension, hyperlipidemia, and osteoporosis as her past medical history. At 5 months before onset, she noticed a decline of her right visual acuity. After that, she visited ophthalmology clinic because her visual acuity was progressively deteriorated to counting finger. In clinic, uveitis complicated with vitreous opacification (VO) was revealed, and subcapsular triamcinolone acetonide was injected for treatment. Although her visual acuity and VO were improved after treatment, she was referred to Osaka University Hospital for detailed examination. Her right visual acuity was 20/50 and left visual acuity was 20/30. Intraocular inflammation and VO were not detected. There were yellowish-white deposits likes hard drusen in her right macula, and OCT showed intraretinal and sub-RPE hyperreflective deposits in the same area. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA, B) However, there were no other abnormal findings through other ophthalmologic examination. Her left eye had no abnormal findings. We decided to observe in our hospital as uveitis of undetermined causes at this time.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOne month later, she visited to our hospital with acute visual exacerbation. Her right visual acuity was hand motion and left visual acuity was 20/30. Intraocular pressure was 18 mmHg in the right eye, and 17 mmHg in the left eye. She had a right afferent pupillary defect. Goldmann visual field perimetry was full in the left eye, but a large dense central scotoma was present in the right eye. (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA, B) Slit lamp examination was normal in the left eye, but optic disc swelling with disc hemorrhage was revealed in the right eye. Yellowish-white deposits likes hard drusen in her right macula was not changed before 1 month. (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC) Any intraocular inflammation and VO were not detected in both eyes. OCT showed prominent disc swelling with intraretinal and subretinal fluid. (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD) Her left eye was normal in the above ophthalmic imaging examination. (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eE, F)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eWe speculated the possibility of infiltrative optic neuropathy, because she had the previous medical history with VO complicated by unknown uveitis. However, a magnetic resonance imaging (MRI) of the head without enhancement did not show hyperintensity and swelling of the optic nerve as well as intracranial lesions. (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA, B) In addition, there was neither VO nor intraocular inflammation at this time. We considered that retinal biopsy for macular or papillary lesions were highly invasive for visual function, so decided to hospitalize the patient for steroid pulse treatment for prominent disc swelling at first. One week after hospitalization, VO occurred and we speculated that the intraretinal and sub-RPE hyperreflective deposits progressed to infiltrative optic nerve neuropathy with VRL. Therefore, we decided to perform 25-gauge microincision vitrectomy for vitreous collection in an emergency. Vitreous specimens were processed for cytology, flow cytometry, and gene rearrangement with the Registration Examination and Analysis Description (READ) system \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. A histological examination indicated a lot of atypical cells with large nuclear/cytoplasm ratios suspected malignant lymphoma. (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA) Findings from the flow cytometry analysis revealed the infiltration of cells positive for CD45, CD19, and CD20, but not CD10 and CD22. Furthermore, the surface immunoglobulin cytochemical analysis revealed monotypic light chain expression restricted kappa chain. (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB) The results of a gene rearrangement analysis were positive for the immunoglobulin heavy locus. Finally, after consideration of all the clinical examinations, a diagnosis was made of infiltrative optic nerve neuropathy with vitreoretinal B-cell lymphoma. Therefore, we decided to treat the patient with the intraocular injection of methotrexate.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIntraocular injection of methotrexate was administered a total of 6 times at intervals of about 2 weeks due to repeated corneal epithelial keratopathy. One month after operation, optic disc swelling and subretinal fluid were markedly improved. (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA, B) At the time of the last visit (6 months after surgery), VO and optic disc swelling had disappeared. In OCT image, intraretinal and sub-RPE deposits were remaining. (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eC, D) Careful observation was continued, but no recurrent findings including MRI was observed, and visual acuity in the right eye at the last visit improved to 20/50.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion and Conclusions","content":"\u003cp\u003eIn the complex landscape of diagnosing optic neuropathy, the rare entity of infiltrative optic neuropathy associated with VRL poses significant challenges. This difficulty is accentuated in cases where the pathological manifestation is confined to the ocular structure, devoid of VO. Our case highlights an instance where the onset of VO, albeit fortuitously post-disease onset, facilitated a vitreous biopsy. This critical intervention enabled the early identification of infiltrative optic neuropathy driven by vitreoretinal B-cell lymphoma. The occurrence of VO not only served as a pivotal diagnostic marker but also underscored the imperative for ophthalmologists to maintain a high level of vigilance for the subtle signs indicating of VRL's early stages.\u003c/p\u003e \u003cp\u003eOCT emerges as a cornerstone in the nuanced diagnosis of optic neuropathy, offering a window to detect early manifestations of VRL. Reports in the literature have elucidated that the appearance of intraretinal and sub-RPE hyperreflective signals as preliminary indicators of the disease, potentially denoting an uptick in disease activity \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. However, the specificity of these signals warrants careful consideration, given their presence in other retinal conditions such as diabetic retinopathy and age-related macular degeneration\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. This necessitates a discerning approach to differentiate these conditions accurately. Moreover, the presence of hyperreflective deposits across various retinal layers, as seen in cases of CNS malignant lymphoma, accentuates their potential as biomarkers for early VRL detection \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. In the presented case, the precursory detection of hyperreflective deposits within the intraretinal and sub-RPE layers, against a background of a medical history devoid of diabetes but inclusive of VO from unclassified uveitis, was instrumental in guiding the provisional diagnosis towards infiltrative optic neuropathy.\u003c/p\u003e \u003cp\u003eThe absence of VO presents a diagnostic challenge, as the yield for malignancy through cytological examination significantly diminishes from 47.1% in the presence of VO to merely 10.0% without VO \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Moreover, considering the high risk associated with retinal biopsies of the optic disc or macula, particularly in terms of visual function, such procedures are deemed highly invasive. Therefore, present case to delay surgical intervention until the manifestation of VO was strategically prudent. This approach aimed to enhance the accuracy of the malignancy diagnosis while concurrently mitigating the risk to the patient\u0026rsquo;s visual function.\u003c/p\u003e \u003cp\u003eIn discussing MRI findings relevant to infiltrative optic neuropathy, it is important to note that even without contrast enhancement, MRI can reveal thickening of the optic nerve, a hallmark of this condition \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Lymphoma infiltration and optic neuritis present similarly on MRI, showing low to iso-intensity on T1 and high intensity on T2-weighted images \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Contrast-enhanced MRIs often show significant enhancement in optic nerve lymphoma cases, with literature noting up to 88% of cases displaying this feature \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. From the above, it is considered that the diagnosis can be made by MRI regardless of contrast enhancement if optic nerve lymphoma is typical case. However, MRI images showed no abnormal findings in our case. As a reason for that, we speculate that the optic nerve lesion is probably still localized in the optic disc, because of very early stage of infiltration from VRL. Moreover, past reports described above described that not all cases have abnormal findings on MRI \u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Therefore, it is necessary to make a comprehensive judgment based on the results of various examination.\u003c/p\u003e \u003cp\u003eIn conclusion, our exploration into the progression of intraretinal and sub-RPE lesions to infiltrative optic nerve neuropathy via OCT substantiates the lesions as forerunners of optic nerve infiltration by VRL. Despite significant therapeutic advancements, the persistence of intraretinal and sub-RPE deposits post-treatment underscores the necessity for continuous monitoring. OCT's indispensable role in differentiating optic neuropathy and the potential CNS spread from VRL necessitate vigilant observation and frequent evaluations to preemptively address any disease advancement, thereby emphasizing the importance of an integrated and proactive diagnostic and management strategy in suspected VRL cases.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eVRL: vitreoretinal lymphoma, CNS: central nervous system, RPE: retinal pigment epithelial, OCT: optical coherence tomography, VO: vitreous opacification, MRI: magnetic resonance imaging\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cu\u003eEthics approval and consent to participate\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatient was provided informed consent using opt-out approach instead of informed written consent. This report does not contain any personal information that could lead to the identification of the patient. The Institutional Review Board of the Osaka University Medical School approved the research protocol, and the procedures conformed to the tenets of the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eConsent for publication\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatient was provided informed consent using opt-out approach instead of informed written consent. This report does not contain any personal information that could lead to the identification of the patient.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003e\u003cu\u003eAvailability of data and materials\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003e\u003cu\u003eCompeting Interest\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there are no conflicts of interest regarding the publication of this paper.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003e\u003cu\u003eFunding\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding or grant support.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003e\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cu\u003eAuthors\u0026rsquo; contributions\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eT.K. and S.K. participated in drafting the manuscript and collection, analysis, and interpretation of the data. S.K. and K.M. participated in diagnosis and treatment of the patient, drafting the manuscript, and revising the manuscript. S.F., T.F., Y.K., H.S., T.M. and K.N. critically reviewed the manuscript and reviewed the literature. All authors consented to their names being published in this report and insist on the intellectual honesty and validity of the data provided. All authors read and approved the final version of the paper.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003e\u003cu\u003eAcknowledgments\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003e\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cu\u003eAuthor\u0026rsquo;s information (optional)\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKim JL, Mendoza PR, Rashid A, Hayek B, Grossniklaus HE. Optic nerve lymphoma: report of two cases and review of the literature. Surv Ophthalmol. 2015 Mar-Apr;60(2):153-65. Doi: 10.1016/j.survophthal.2014.11.004. Epub 2014 Dec 18. PMID: 25595061; PMCID: PMC4334739.\u003c/li\u003e\n\u003cli\u003eGill MK, Jampol LM. Variations in the presentation of primary intraocular lymphoma: case reports and a review. Surv Ophthalmol. 2001 May-Jun;45(6):463-71. Doi: 10.1016/s0039-6257(01)00217-x. PMID: 11425352. \u003c/li\u003e\n\u003cli\u003eLiu, T.Y.A., Ibrahim, M., Bittencourt, M. \u003cem\u003eet al.\u003c/em\u003e Retinal optical coherence tomography manifestations of intraocular lymphoma. \u003cem\u003eJ Ophthal Inflamm Infect\u003c/em\u003e \u003cstrong\u003e2\u003c/strong\u003e, 215\u0026ndash;218 (2012). https://doi.org/10.1007/s12348-012-0072-z\u003c/li\u003e\n\u003cli\u003eHassan, M., Halim, M.S., Afridi, R. \u003cem\u003eet al.\u003c/em\u003e Evaluating optical coherence tomography (OCT) findings as potential biomarkers in central nervous system (CNS) lymphoma with or without ocular involvement. \u003cem\u003eInt J Retin Vitr\u003c/em\u003e \u003cstrong\u003e7\u003c/strong\u003e, 70 (2021). https://doi.org/10.1186/s40942-021-00345-1 \u003c/li\u003e\n\u003cli\u003eOtomo T, Fuse N, Ishizawa K, Seimiya M, Shimura M, Ryo Ichinohazama. Japanese case of follicular lymphoma of ocular adnexa diagnosed by clinicopathologic, immunohistochemical, and molecular genetic techniques. \u003cem\u003eClin Ophthalmol\u003c/em\u003e. 2010;4:1397-1402 https://doi.org/10.2147/OPTH.S15219)\u003c/li\u003e\n\u003cli\u003eJang, H.S., Sepah, Y.J., Sophie, R. \u003cem\u003eet al.\u003c/em\u003e Longitudinal spectral domain optical coherence tomography changes in eyes with intraocular lymphoma. \u003cem\u003eJ Ophthal Inflamm Infect\u003c/em\u003e \u003cstrong\u003e3\u003c/strong\u003e, 59 (2013). https://doi.org/10.1186/1869-5760-3-59\u003c/li\u003e\n\u003cli\u003eFolgar FA, Chow JH, Farsiu S, Wong WT, Schuman SG, O\u0026rsquo;Connell RV, Winter KP, Chew EY, Hwang TS, Srivastava SK, Harrington MW, Clemons TE, Toth CA. Spatial correlation between hyperpigmentary changes on color fundus photography and hyperreflective foci on SDOCT in intermediate AMD. Invest Ophthalmol Vis Sci. 2012 Jul 9;53(8):4626-33. Doi: 10.1167/iovs.12-9813. PMID: 22589439. \u003c/li\u003e\n\u003cli\u003eBolz M, Schmidt-Erfurth U, Deak G, Mylonas G, Kriechbaum K, Scholda C; Diabetic Retinopathy Research Group Vienna. Optical coherence tomographic hyperreflective foci: a morphologic sign of lipid extravasation in diabetic macular edema. Ophthalmology. 2009 May;116(5):914-20. Doi: 10.1016/j.ophtha.2008.12.039. PMID: 19410950.\u003c/li\u003e\n\u003cli\u003eKimura K, Usui Y, Goto H; Japanese Intraocular Lymphoma Study Group. Clinical features and diagnostic significance of the intraocular fluid of 217 patients with intraocular lymphoma. Jpn J Ophthalmol. 2012 Jul;56(4):383-9. Doi: 10.1007/s10384-012-0150-7. Epub 2012 Jun 5. PMID: 22661396.\u003c/li\u003e\n\u003cli\u003eYo Han Ra, Sun Young Park, Soo Ah Im, Jee Young Kim, Nak Gyun Chung, and Bin Cho; Enhancement of Optic Nerve in Leukemic Patients: Leukemic Infiltration of Optic Nerve versus Optic Neuritis. Investig Magn Reson Imaging. 2016 Sep;20(3):167-174. https://doi.org/10.13104/imri.2016.20.3.167\u003c/li\u003e\n\u003cli\u003eAhle G, Touitou V, Cassoux N, et al. Optic Nerve Infiltration in Primary Central Nervous System Lymphoma. \u003cem\u003eJAMA Neurol.\u003c/em\u003e 2017;74(11):1368\u0026ndash;1373. Doi:10.1001/jamaneurol.2017.2545\u003c/li\u003e\n\u003cli\u003eYang M, Zhao J, Song H, Wei S, Zhou H, Xu Q. Orbital Magnetic Resonance Imaging May Contribute to the Diagnosis of Optic Nerve Lymphoma. Front Neurol. 2020 Apr 28;11:301. Doi: 10.3389/fneur.2020.00301. PMID: 32411078; PMCID: PMC7198801.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"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":"Infiltrative optic neuropathy, vitreoretinal lymphoma, optical coherence tomography, hyperreflective deposits","lastPublishedDoi":"10.21203/rs.3.rs-4244258/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4244258/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eTo describe a rare case of infiltrative optic neuropathy caused by vitreoretinal lymphoma (VRL) with intraretinal and subretinal pigmented epithelial (RPE) hyperreflective deposits before the disease onset.\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e \u003cp\u003eWe presented an 87-year-old Japanese female. At 5 months before onset, she noticed a decline of her right visual acuity, and she visited ophthalmology clinic because her visual acuity was progressively deteriorated to counting finger. In clinic, uveitis complicated with vitreous opacification (VO) was revealed, and subcapsular triamcinolone acetonide was injected for treatment. Although her visual acuity and VO were improved after treatment, she was referred to Osaka University Hospital for detailed examination. Her right visual acuity was 20/50. Intraocular inflammation and VO were not detected. There were yellowish-white deposits likes hard drusen in her right macula, and optical coherence tomography (OCT) showed intraretinal and sub-RPE hyperreflective deposits in the same area. One month later, she visited to our hospital with acute visual exacerbation. Her right visual acuity was hand motion. Optic disc swelling with disc hemorrhage was shown in the right eye. There was neither VO nor intraocular inflammation at this time, and a magnetic resonance imaging (MRI) of the head without enhancement did not show hyperintensity and swelling of the optic nerve as well as intracranial lesions. One week later, VO occurred and we performed 25-gauge vitrectomy for vitreous collection. Finally, after consideration of all the clinical examinations, a diagnosis was made of infiltrative optic nerve neuropathy with vitreoretinal B-cell lymphoma. Intraocular injection of methotrexate was administered a total of 6 times. At the time of the last visit (6 months after surgery), VO and optic disc swelling had disappeared. Careful observation was continued, but no recurrent findings including MRI was observed, and visual acuity in the right eye improved to 20/50.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eAlthough there were reports on VRL advanced from intraretinal or sub-RPE hyperreflective deposits, there have been no studies that these OCT findings has progressed to infiltrative optic nerve neuropathy with VRL. When differentiating optic neuropathy, OCT may assist in the diagnosis by evaluating intraretinal and sub-RPE findings.\u003c/p\u003e","manuscriptTitle":"A rare case of infiltrative optic neuropathy caused by vitreoretinal lymphoma with intraretinal and subretinal pigmented epithelial hyperreflective deposits prior to the disease onset","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-19 18:29:56","doi":"10.21203/rs.3.rs-4244258/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":"dd504897-72ae-4cd4-9008-5181112e8863","owner":[],"postedDate":"April 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-20T15:32:17+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-19 18:29:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4244258","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4244258","identity":"rs-4244258","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}