Unilateral serous macular detachment accompanying cystoid macular edema temporally associated with COVID-19 vaccination: A case report

Unilateral serous macular detachment accompanying cystoid macular edema temporally associated with COVID-19 vaccination: A case report | 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 Unilateral serous macular detachment accompanying cystoid macular edema temporally associated with COVID-19 vaccination: A case report Navid Elmi Sadr, Ramyar Hariri This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3474127/v2 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Jun, 2025 Read the published version in Duke Journal of Case Reports in Ophthalmology → Version 2 posted You are reading this latest preprint version Show more versions Abstract Objective : To report a case of unilateral serous macular detachment accompanying cystoid macular edema temporally associated with COVID-19 vaccination. Methods: Case report. Case description : A 67-year-old male presented with progressive vision loss in his left eye seven days after receiving the second dose of the COVID-19 vaccine (BBIBP-CorV, Sinopharm, Beijing, China). Fundus examination and spectral-domain optical coherence tomography angiography (SD-OCTA; Optovue, Fremont, CA) showed serous macular detachment with cystoid macular edema (CME) in the left eye. The patient’s best-corrected visual acuity improved dramatically from counting fingers at 3 m to 20/32, and macular detachment and CME resolved significantly within 10 days, without any treatment. Conclusion : This observation suggests a potential link between transient serous macular detachment accompanying CME and the Sinopharm COVID-19 vaccination. Nevertheless, it is important to emphasize that vaccination against COVID-19 is highly recommended. Ophthalmology COVID-19 cystoid macular edema serous macular detachment Sinopharm vaccination Figures Figure 1 Figure 2 Figure 3 Introduction COVID-19, caused by SARS-CoV-2, became the primary global concern for nearly three years. The burden of the pandemic made the global health system face urgent calls for the development of vaccines. In the relatively short period that COVID-19 vaccines have been in use, a number of ocular adverse events have been reported. These include ophthalmic vein thrombosis, acute macular neuroretinopathy, multiple evanescent white dot syndrome, paracentral acute middle maculopathy, bilateral multifocal choroiditis, Vogt-Koyanagi-Harada disease, new-onset Graves' disease, central serous chorioretinopathy, uveitis, corneal graft rejection, scleritis and episcleritis, facial nerve palsy, and abducens nerve palsy [1,2]. Herein, we report an unusual case of unilateral serous macular detachment accompanied by cystoid macular edema (CME), which occurred in close temporal association with the administration of a second dose of the Sinopharm COVID-19 vaccine. Case description A 67-year-old male presented with progressive, painless vision loss in his left eye, noticed approximately 48 hours before presentation. He had received the second dose of Sinopharm COVID-19 vaccine seven days earlier. He had no systemic symptoms except mild generalized myalgia for the first two days post-vaccination. His medical history included benign prostatic hyperplasia, hypertension, and ischemic heart disease. There was no previous history of ocular, systemic autoimmune, or infectious diseases. He was taking medications, including warfarin, acetylsalicylic acid (ASA), losartan, hydrochlorothiazide, carvedilol, atorvastatin, tamsulosin, and finasteride. His blood pressure at the time of examination was 135/85 mmHg. His best-corrected visual acuity was 20/20 in the right eye and counting fingers at 3 m in the left eye. Slit-lamp biomicroscopy revealed mild nuclear cataracts in both eyes. Fundus examination revealed sensory retinal detachment in the macular area of the left eye. The optic nerve head and retinal periphery appeared to be normal bilaterally. Spectral-domain optical coherence tomography angiography (SD-OCTA; Optovue, Fremont, CA) showed massive serous retinal detachment and CME with a lack of flow pixels in the choriocapillaris in the left eye (Fig. 1 ). OCT examination of the right eye revealed normal foveal structures (Fig. 2 ). Other fundus imaging modalities, including fundus camera, fluorescein angiography, and indocyanine green angiography, were not available at that time. A reverse transcription polymerase chain reaction (RT-PCR) test for COVID-19 using nasopharyngeal swab sampling was performed, and the result was negative. Laboratory test results, including complete blood count, erythrocyte sedimentation rate, and C-reactive protein levels, were within normal limits. On follow-up fundus examination, the amount of subretinal fluid had decreased gradually. Finally, on follow-up day 10, macular detachment was not detectable on slit-lamp biomicroscopy and the best-corrected visual acuity improved to 20/32. The patient was completely satisfied with his improved vision and refused to undergo a new OCT examination. Six weeks and 16 weeks after the initial ocular examination, the best-corrected visual acuity was 20/25. The second and third OCT examinations of the left eye revealed neither subretinal fluid nor CME (Fig. 3 ). The central subfield thickness decreased from 683 to 232 µm, and the flow signal at choriocapillaris became normal. However, the outer segments showed irregularities compared with the right eye. Complete OCT and OCTA images are available at the Harvard Dataverse repository ( https://doi.org/10.7910/DVN/FUA8WC ). Discussion COVID-19 is a systemic infection that can lead to life-threatening multi-organ involvement.[3] (WHO) listed the BBIBP-CorV (Sinopharm), an aluminum-hydroxide-adjuvanted inactivated whole virus vaccine, for emergency use on May 7, 2021, for adults 18 years and older. Two doses of the vaccine with a spacing of three-four weeks have an efficacy of 79% against symptomatic SARS-CoV-2 infection and hospitalization two weeks or more after the second dose [4]. Beyond the outweighing benefits, rare ocular adverse events that are temporally associated with the vaccine have been reported. Pichi et al. in a case series reported episcleritis (one case), anterior scleritis (two cases), acute macular neuroretinopathy (two cases), paracentral acute middle maculopathy (one case), and subretinal fluid (one case) in seven patients, which occurred within two weeks after receiving the Sinopharm COVID-19 vaccine [2]. In our patient, unilateral serous macular detachment and CME were diagnosed one week after the second dose of the Sinopharm COVID-19 vaccination and resolved spontaneously and gradually within 10 days. Serous retinal detachment accompanying macular edema has been observed in diabetic macular edema, retinal vein occlusion, uveitis, chronic central serous chorioretinopathy, choroidal vascular lesions, intracameral cefuroxime toxicity, Coats' disease, Waldenström macroglobulinemia, and hypotony maculopathy [5–11]. The authors did not observe any findings related to the aforementioned differential diagnoses. Our patient was taking several medications, some of which have been linked to macular abnormalities. The results of an earlier case-control study indicated a potential association between 5-alpha reductase inhibitors, specifically finasteride, and the development of cystoid macular abnormalities and foveal cavitation, which may progress to the formation of a macular hole [12]. A case report indicated that hydrochlorothiazide may be associated with macular edema. Notably, the macular edema observed was bilateral and not accompanied by serous retinal detachment. Importantly, the edema resolved at three months with discontinuation of the medication, implying that it may not be relevant to the current case [13]. It is well known that tight junctions between endothelial cells of retinal vessels and between retinal pigment epithelium form the inner blood-retinal barrier (BRB) and outer BRB, respectively. Damage to the inner BRB and subsequent increased permeability of the retinal capillary plexus lead to macular edema. Furthermore, outer BRB disruption causes subretinal fluid accumulation. Cytokines and other pro-inflammatory mediators can lead to BRB dysfunction with or without structural vascular alterations. Degranulation of the mast cells, residing beside choroidal vessels, and the consequent release of histamine is another important cause of outer BRB alteration [14]. Although vaccines containing live-attenuated viruses have the potential to transform to a wild type, especially in immunocompromised patients, most of the post-vaccination adverse events are immune-mediated. Microbial antigens or adjuvants (e.g., aluminum salts) and other additional components, present in vaccines, can trigger allergy and autoimmunity [15]. Most post-vaccination allergic reactions are immediate and IgE-mediated. Possible non-IgE-mediated reactions to vaccines are categorized under the term adverse events following immunization (AEFI) [16]. Thus, in the patient reported here, a transient inflammatory process or allergic reaction induced by the vaccine could have led to inner and outer BRBs dysfunction and subsequent intraretinal and subretinal fluid accumulation. The resolution of the acute phase of inflammation and clearance of inflammatory and allergic mediators may explain the spontaneous resolution of fluid accumulation. However, owing to the lack of fluorescein and indocyanine green angiography reports, other causes cannot be definitively ruled out. Conclusion This report raises the possibility that the Sinopharm COVID-19 vaccination may be associated with transient and self-limited serous macular detachment accompanying CME. Despite this, vaccination against COVID-19 is strongly recommended, and additional reports are needed to prove the causative relationship and define the exact pathophysiological mechanism. Declarations Consent to publish the study was provided by the participant. Acknowledgment: We would like to thank the Clinical Research Development Unit of Kowsar Educational and Research and Therapeutic Center of Semnan University of Medical Sciences for providing facilities to this work. We extend our thanks to Bahareh Bineshian for her valuable contribution to language editing of the manuscript. Competing interests: The authors report no conflict of interest. Ethics declaration: This report followed the tenets of the Declaration of Helsinki, and was approved by the Institutional Ethics Committee (IR.SEMUMS.REC.1400.167). Written informed consent have been obtained from the patient. Authors’ contributions: NES approved the diagnostic and management interventions for the patient. NES and RH created the first drafts of the manuscript, and finalized and approved the submitted version. References Ng XL, Betzler BK, Testi I, et al.: Ocular Adverse Events After COVID-19 Vaccination. Ocular immunology and inflammation. 2021, 29:1216-1224. 10.1080/09273948.2021.1976221 Pichi F, Aljneibi S, Neri P, Hay S, Dackiw C, Ghazi NG: Association of Ocular Adverse Events With Inactivated COVID-19 Vaccination in Patients in Abu Dhabi. JAMA ophthalmology. 2021, 139:1131-1135. 10.1001/jamaophthalmol.2021.3477 Rello J, Belliato M, Dimopoulos MA, et al.: Update in COVID-19 in the intensive care unit from the 2020 HELLENIC Athens International symposium. Anaesthesia, critical care & pain medicine. 2020, 39:723-730. 10.1016/j.accpm.2020.10.008 Interim recommendations for use of the inactivated COVID-19 vaccine BIBP developed by China National Biotec Group (CNBG), Sinopharm-7 May 2021. https://www.who.int/publications/i/item/WHO-2019-nCoV-vaccines-SAGE_recommendation-BIBP-2021.1. Accorinti M, Okada AA, Smith JR, Gilardi M: Epidemiology of Macular Edema in Uveitis. Ocular immunology and inflammation. 2019, 27:169-180. 10.1080/09273948.2019.1576910 Baker PS, Garg SJ, Fineman MS, et al.: Serous macular detachment in Waldenström macroglobulinemia: a report of four cases. American journal of ophthalmology. 2013, 155:448-455. 10.1016/j.ajo.2012.09.018 Chlasta-Twardzik E, Nowińska A, Wylęgała E: Acute macular edema and serous detachment on the first day after phacoemulsification surgery: A case report. American journal of ophthalmology case reports. 2020, 20:100905. 10.1016/j.ajoc.2020.100905 Kokame GT, de Leon MD, Tanji T: Serous retinal detachment and cystoid macular edema in hypotony maculopathy. American journal of ophthalmology. 2001, 131:384-386. 10.1016/s0002-9394(00)00794-7 Muraoka Y, Murakami T, Nishijima K, et al.: Association between retinal venular dilation and serous retinal detachment in diabetic macular edema. Retina. 2014, 34:725-731. 10.1097/IAE.0b013e3182a48732 Otani T, Yamaguchi Y, Kishi S: Serous macular detachment secondary to distant retinal vascular disorders. Retina. 2004, 24:758-762. 10.1097/00006982-200410000-00012 van Rijssen TJ, van Dijk EHC, Yzer S, et al.: Central serous chorioretinopathy: Towards an evidence-based treatment guideline. Progress in retinal and eye research. 2019, 73:100770. 10.1016/j.preteyeres.2019.07.003 Shin YK, Lee GW, Kang SW, Kim SJ, Kim AY: Macular Abnormalities Associated With 5α-Reductase Inhibitor. JAMA ophthalmology. 2020, 138:732-739. 10.1001/jamaophthalmol.2020.1279 Iacono P, Battaglia Parodi M, Bandello F: Macular edema associated with hydrochlorothiazide therapy. The British journal of ophthalmology. 2011, 95:1025, 1036-1027. 10.1136/bjo.2009.164954 Daruich A, Matet A, Moulin A, et al.: Mechanisms of macular edema: Beyond the surface. Progress in retinal and eye research. 2018, 63:20-68. 10.1016/j.preteyeres.2017.10.006 Cheng JY, Margo CE: Ocular adverse events following vaccination: overview and update. Survey of ophthalmology. 2022, 67:293-306. 10.1016/j.survophthal.2021.04.001 Dreskin SC, Halsey NA, Kelso JM, et al.: International Consensus (ICON): allergic reactions to vaccines. The World Allergy Organization journal. 2016, 9:32. 10.1186/s40413-016-0120-5 Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Published Journal Publication published 01 Jun, 2025 Read the published version in Duke Journal of Case Reports in Ophthalmology → Version 2 posted You are reading this latest preprint version Show more versions 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-3474127","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":417509871,"identity":"bfd915f8-6f5a-4619-aa12-538fd4dfb706","order_by":0,"name":"Navid Elmi Sadr","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBElEQVRIiWNgGAWjYJCCAzwMDDIMzCAmG4McWOQBEVp4YFqMwSIJhKwBa2GAaElsANH4tJiznzE88IbBhke3nYH5w4+ye+nzww4/BNpiJ6fbgF2LZU+OwcE5DGk8ZocZ2CR7zhXnbrydZgDUkmxsdgC7FoMDaQmHeRgOg7Uw8LYl5G6cnQDSciBxGy4t55+BtPwHaWH++LctId1wdvoH/FpuJB8AajkA0sIgDbQlQV46h4AtNx4fODjHIBmohbFNWuZcguEG6ZyCAwkGePxyPrH5w5sKOzmz84cPf3xTliAvPzt984cPIBEcWqAaQQRjAzRA4CLEAvkGUlSPglEwCkbBSAAANmVgLDcmXgsAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0001-5641-4390","institution":"Semnan University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Navid","middleName":"Elmi","lastName":"Sadr","suffix":""},{"id":417509872,"identity":"0a3f712c-d0c0-45e1-a5a9-53c5f4060e25","order_by":1,"name":"Ramyar Hariri","email":"","orcid":"","institution":"Semnan University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Ramyar","middleName":"","lastName":"Hariri","suffix":""}],"badges":[],"createdAt":"2023-10-21 14:38:26","currentVersionCode":2,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":true,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":true,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-3474127/v2","doiUrl":"https://doi.org/10.21203/rs.3.rs-3474127/v2","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.62856/djcro.v7.48","type":"published","date":"2025-06-02T00:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":76571924,"identity":"3064c912-14e4-49c9-9774-66b4b659264c","added_by":"auto","created_at":"2025-02-05 09:18:55","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":724707,"visible":true,"origin":"","legend":"\u003cp\u003eThe first optical coherence tomography (OCT) angiography of the left eye. The first OCT B-scan of the left eye (bottom row) showed the subretinal fluid (yellow asterisk) and cystoid hyporeflective spaces (red asterisk) in the macular area. The en-face angio/OCT images (top row) showed no flow abnormalities in the superficial, deep, and outer retina. Note that the lack of flow pixels in the choriocapillaris resulted from segmentation error caused by the presence of intraretinal and subretinal fluid.\u003c/p\u003e","description":"","filename":"figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5923789/v1/5ecfc31f99ea7cf9db054c4a.jpg"},{"id":76571929,"identity":"35952017-16f7-4ad0-92b8-f095e74e5ce8","added_by":"auto","created_at":"2025-02-05 09:26:55","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":757416,"visible":true,"origin":"","legend":"\u003cp\u003eThe first optical coherence tomography (OCT) angiography of the right eye showing normal foveal structures.\u003c/p\u003e","description":"","filename":"figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5923789/v1/693daa6811df6b6700afd791.jpg"},{"id":76571931,"identity":"8dd8b391-ec8b-4e85-9b02-ba7d9fb2732e","added_by":"auto","created_at":"2025-02-05 09:26:55","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":786965,"visible":true,"origin":"","legend":"\u003cp\u003eThe second optical coherence tomography (OCT) angiography of the left eye. The second OCT B-scan of the left eye (middle row), six weeks apart, showed cystoid macular edema and subretinal fluid resolution. However, the outer segments showed irregularities and thickening (black arrows). The en-face angio/OCT images (top row) showed normal flow signals in the superficial, deep, and outer retina. Note that some motion artifacts were present.\u003c/p\u003e","description":"","filename":"figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5923789/v1/fd3b46fb3a64ea5265b56886.jpg"},{"id":83929800,"identity":"a9aed5a6-62cc-43ed-b9c6-72e987b6dd08","added_by":"auto","created_at":"2025-06-04 15:11:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2608348,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3474127/v2/6ca8addd-c5ef-438a-9c72-6c7a89ac4a9a.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"Unilateral serous macular detachment accompanying cystoid macular edema temporally associated with COVID-19 vaccination: A case report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCOVID-19, caused by SARS-CoV-2, became the primary global concern for nearly three years. The burden of the pandemic made the global health system face urgent calls for the development of vaccines. In the relatively short period that COVID-19 vaccines have been in use, a number of ocular adverse events have been reported. These include ophthalmic vein thrombosis, acute macular neuroretinopathy, multiple evanescent white dot syndrome, paracentral acute middle maculopathy, bilateral multifocal choroiditis, Vogt-Koyanagi-Harada disease, new-onset Graves' disease, central serous chorioretinopathy, uveitis, corneal graft rejection, scleritis and episcleritis, facial nerve palsy, and abducens nerve palsy [1,2]. Herein, we report an unusual case of unilateral serous macular detachment accompanied by cystoid macular edema (CME), which occurred in close temporal association with the administration of a second dose of the Sinopharm COVID-19 vaccine.\u003c/p\u003e"},{"header":"Case description","content":"\u003cp\u003eA 67-year-old male presented with progressive, painless vision loss in his left eye, noticed approximately 48 hours before presentation. He had received the second dose of Sinopharm COVID-19 vaccine seven days earlier. He had no systemic symptoms except mild generalized myalgia for the first two days post-vaccination. His medical history included benign prostatic hyperplasia, hypertension, and ischemic heart disease. There was no previous history of ocular, systemic autoimmune, or infectious diseases. He was taking medications, including warfarin, acetylsalicylic acid (ASA), losartan, hydrochlorothiazide, carvedilol, atorvastatin, tamsulosin, and finasteride.\u003c/p\u003e\n\u003cp\u003eHis blood pressure at the time of examination was 135/85 mmHg. His best-corrected visual acuity was 20/20 in the right eye and counting fingers at 3 m in the left eye. Slit-lamp biomicroscopy revealed mild nuclear cataracts in both eyes. Fundus examination revealed sensory retinal detachment in the macular area of the left eye. The optic nerve head and retinal periphery appeared to be normal bilaterally.\u003c/p\u003e\n\u003cp\u003eSpectral-domain optical coherence tomography angiography (SD-OCTA; Optovue, Fremont, CA) showed massive serous retinal detachment and CME with a lack of flow pixels in the choriocapillaris in the left eye (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). OCT examination of the right eye revealed normal foveal structures (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Other fundus imaging modalities, including fundus camera, fluorescein angiography, and indocyanine green angiography, were not available at that time.\u003c/p\u003e\n\u003cp\u003eA reverse transcription polymerase chain reaction (RT-PCR) test for COVID-19 using nasopharyngeal swab sampling was performed, and the result was negative. Laboratory test results, including complete blood count, erythrocyte sedimentation rate, and C-reactive protein levels, were within normal limits. On follow-up fundus examination, the amount of subretinal fluid had decreased gradually. Finally, on follow-up day 10, macular detachment was not detectable on slit-lamp biomicroscopy and the best-corrected visual acuity improved to 20/32. The patient was completely satisfied with his improved vision and refused to undergo a new OCT examination.\u003c/p\u003e\n\u003cp\u003eSix weeks and 16 weeks after the initial ocular examination, the best-corrected visual acuity was 20/25. The second and third OCT examinations of the left eye revealed neither subretinal fluid nor CME (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). The central subfield thickness decreased from 683 to 232 \u0026micro;m, and the flow signal at choriocapillaris became normal. However, the outer segments showed irregularities compared with the right eye.\u003c/p\u003e\n\u003cp\u003eComplete OCT and OCTA images are available at the Harvard Dataverse repository (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.7910/DVN/FUA8WC\u003c/span\u003e\u003c/span\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCOVID-19 is a systemic infection that can lead to life-threatening multi-organ involvement.[3] (WHO) listed the BBIBP-CorV (Sinopharm), an aluminum-hydroxide-adjuvanted inactivated whole virus vaccine, for emergency use on May 7, 2021, for adults 18 years and older. Two doses of the vaccine with a spacing of three-four weeks have an efficacy of 79% against symptomatic SARS-CoV-2 infection and hospitalization two weeks or more after the second dose [4]. Beyond the outweighing benefits, rare ocular adverse events that are temporally associated with the vaccine have been reported. Pichi et al. in a case series reported episcleritis (one case), anterior scleritis (two cases), acute macular neuroretinopathy (two cases), paracentral acute middle maculopathy (one case), and subretinal fluid (one case) in seven patients, which occurred within two weeks after receiving the Sinopharm COVID-19 vaccine [2]. In our patient, unilateral serous macular detachment and CME were diagnosed one week after the second dose of the Sinopharm COVID-19 vaccination and resolved spontaneously and gradually within 10 days. Serous retinal detachment accompanying macular edema has been observed in diabetic macular edema, retinal vein occlusion, uveitis, chronic central serous chorioretinopathy, choroidal vascular lesions, intracameral cefuroxime toxicity, Coats' disease, Waldenstr\u0026ouml;m macroglobulinemia, and hypotony maculopathy [5\u0026ndash;11]. The authors did not observe any findings related to the aforementioned differential diagnoses.\u003c/p\u003e \u003cp\u003eOur patient was taking several medications, some of which have been linked to macular abnormalities. The results of an earlier case-control study indicated a potential association between 5-alpha reductase inhibitors, specifically finasteride, and the development of cystoid macular abnormalities and foveal cavitation, which may progress to the formation of a macular hole [12]. A case report indicated that hydrochlorothiazide may be associated with macular edema. Notably, the macular edema observed was bilateral and not accompanied by serous retinal detachment. Importantly, the edema resolved at three months with discontinuation of the medication, implying that it may not be relevant to the current case [13].\u003c/p\u003e \u003cp\u003eIt is well known that tight junctions between endothelial cells of retinal vessels and between retinal pigment epithelium form the inner blood-retinal barrier (BRB) and outer BRB, respectively. Damage to the inner BRB and subsequent increased permeability of the retinal capillary plexus lead to macular edema. Furthermore, outer BRB disruption causes subretinal fluid accumulation. Cytokines and other pro-inflammatory mediators can lead to BRB dysfunction with or without structural vascular alterations. Degranulation of the mast cells, residing beside choroidal vessels, and the consequent release of histamine is another important cause of outer BRB alteration [14]. Although vaccines containing live-attenuated viruses have the potential to transform to a wild type, especially in immunocompromised patients, most of the post-vaccination adverse events are immune-mediated. Microbial antigens or adjuvants (e.g., aluminum salts) and other additional components, present in vaccines, can trigger allergy and autoimmunity [15].\u003c/p\u003e \u003cp\u003eMost post-vaccination allergic reactions are immediate and IgE-mediated. Possible non-IgE-mediated reactions to vaccines are categorized under the term adverse events following immunization (AEFI) [16]. Thus, in the patient reported here, a transient inflammatory process or allergic reaction induced by the vaccine could have led to inner and outer BRBs dysfunction and subsequent intraretinal and subretinal fluid accumulation. The resolution of the acute phase of inflammation and clearance of inflammatory and allergic mediators may explain the spontaneous resolution of fluid accumulation. However, owing to the lack of fluorescein and indocyanine green angiography reports, other causes cannot be definitively ruled out.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis report raises the possibility that the Sinopharm COVID-19 vaccination may be associated with transient and self-limited serous macular detachment accompanying CME. Despite this, vaccination against COVID-19 is strongly recommended, and additional reports are needed to prove the causative relationship and define the exact pathophysiological mechanism.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eConsent to publish the study was provided by the participant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment:\u0026nbsp;\u003c/strong\u003eWe would like to thank the Clinical Research Development Unit of Kowsar Educational and Research and Therapeutic Center of Semnan University of Medical Sciences for providing facilities to this work. We extend our thanks to Bahareh Bineshian for her valuable contribution to language editing of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors report no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics declaration:\u003c/strong\u003e This report followed the tenets of the Declaration of Helsinki, and was approved by the Institutional Ethics Committee (IR.SEMUMS.REC.1400.167). Written informed consent have been obtained from the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions:\u003c/strong\u003e NES approved the diagnostic and management interventions for the patient. NES and RH created the first drafts of the manuscript, and finalized and approved the submitted version.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eNg XL, Betzler BK, Testi I, et al.: Ocular Adverse Events After COVID-19 Vaccination. Ocular immunology and inflammation. 2021, 29:1216-1224. 10.1080/09273948.2021.1976221\u003c/li\u003e\n\u003cli\u003ePichi F, Aljneibi S, Neri P, Hay S, Dackiw C, Ghazi NG: Association of Ocular Adverse Events With Inactivated COVID-19 Vaccination in Patients in Abu Dhabi. JAMA ophthalmology. 2021, 139:1131-1135. 10.1001/jamaophthalmol.2021.3477\u003c/li\u003e\n\u003cli\u003eRello J, Belliato M, Dimopoulos MA, et al.: Update in COVID-19 in the intensive care unit from the 2020 HELLENIC Athens International symposium. Anaesthesia, critical care \u0026amp; pain medicine. 2020, 39:723-730. 10.1016/j.accpm.2020.10.008\u003c/li\u003e\n\u003cli\u003eInterim recommendations for use of the inactivated COVID-19 vaccine BIBP developed by China National Biotec Group (CNBG), Sinopharm-7 May 2021. https://www.who.int/publications/i/item/WHO-2019-nCoV-vaccines-SAGE_recommendation-BIBP-2021.1.\u003c/li\u003e\n\u003cli\u003eAccorinti M, Okada AA, Smith JR, Gilardi M: Epidemiology of Macular Edema in Uveitis. Ocular immunology and inflammation. 2019, 27:169-180. 10.1080/09273948.2019.1576910\u003c/li\u003e\n\u003cli\u003eBaker PS, Garg SJ, Fineman MS, et al.: Serous macular detachment in Waldenstr\u0026ouml;m macroglobulinemia: a report of four cases. American journal of ophthalmology. 2013, 155:448-455. 10.1016/j.ajo.2012.09.018\u003c/li\u003e\n\u003cli\u003eChlasta-Twardzik E, Nowińska A, Wylęgała E: Acute macular edema and serous detachment on the first day after phacoemulsification surgery: A case report. American journal of ophthalmology case reports. 2020, 20:100905. 10.1016/j.ajoc.2020.100905\u003c/li\u003e\n\u003cli\u003eKokame GT, de Leon MD, Tanji T: Serous retinal detachment and cystoid macular edema in hypotony maculopathy. American journal of ophthalmology. 2001, 131:384-386. 10.1016/s0002-9394(00)00794-7\u003c/li\u003e\n\u003cli\u003eMuraoka Y, Murakami T, Nishijima K, et al.: Association between retinal venular dilation and serous retinal detachment in diabetic macular edema. Retina. 2014, 34:725-731. 10.1097/IAE.0b013e3182a48732\u003c/li\u003e\n\u003cli\u003eOtani T, Yamaguchi Y, Kishi S: Serous macular detachment secondary to distant retinal vascular disorders. Retina. 2004, 24:758-762. 10.1097/00006982-200410000-00012\u003c/li\u003e\n\u003cli\u003evan Rijssen TJ, van Dijk EHC, Yzer S, et al.: Central serous chorioretinopathy: Towards an evidence-based treatment guideline. Progress in retinal and eye research. 2019, 73:100770. 10.1016/j.preteyeres.2019.07.003\u003c/li\u003e\n\u003cli\u003eShin YK, Lee GW, Kang SW, Kim SJ, Kim AY: Macular Abnormalities Associated With 5\u0026alpha;-Reductase Inhibitor. JAMA ophthalmology. 2020, 138:732-739. 10.1001/jamaophthalmol.2020.1279\u003c/li\u003e\n\u003cli\u003eIacono P, Battaglia Parodi M, Bandello F: Macular edema associated with hydrochlorothiazide therapy. The British journal of ophthalmology. 2011, 95:1025, 1036-1027. 10.1136/bjo.2009.164954\u003c/li\u003e\n\u003cli\u003eDaruich A, Matet A, Moulin A, et al.: Mechanisms of macular edema: Beyond the surface. Progress in retinal and eye research. 2018, 63:20-68. 10.1016/j.preteyeres.2017.10.006\u003c/li\u003e\n\u003cli\u003eCheng JY, Margo CE: Ocular adverse events following vaccination: overview and update. Survey of ophthalmology. 2022, 67:293-306. 10.1016/j.survophthal.2021.04.001\u003c/li\u003e\n\u003cli\u003eDreskin SC, Halsey NA, Kelso JM, et al.: International Consensus (ICON): allergic reactions to vaccines. The World Allergy Organization journal. 2016, 9:32. 10.1186/s40413-016-0120-5\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"Semnan University of Medical Sciences","isAcceptedByJournal":true,"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":"COVID-19, cystoid macular edema, serous macular detachment, Sinopharm, vaccination","lastPublishedDoi":"10.21203/rs.3.rs-3474127/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3474127/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e: To report a case of unilateral serous macular detachment accompanying cystoid macular edema temporally associated with COVID-19 vaccination.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eCase report.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase description\u003c/strong\u003e: A 67-year-old male presented with progressive vision loss in his left eye seven days after receiving the second dose of the COVID-19 vaccine (BBIBP-CorV, Sinopharm, Beijing, China). Fundus examination and spectral-domain optical coherence tomography angiography (SD-OCTA; Optovue, Fremont, CA) showed serous macular detachment with cystoid macular edema (CME) in the left eye. The patient’s best-corrected visual acuity improved dramatically from counting fingers at 3 m to 20/32, and macular detachment and CME resolved significantly within 10 days, without any treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: This observation suggests a potential link between transient serous macular detachment accompanying CME and the Sinopharm COVID-19 vaccination. Nevertheless, it is important to emphasize that vaccination against COVID-19 is highly recommended.\u003c/p\u003e","manuscriptTitle":"Unilateral serous macular detachment accompanying cystoid macular edema temporally associated with COVID-19 vaccination: A case report","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2025-02-05 09:18:51","doi":"10.21203/rs.3.rs-3474127/v2","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}},{"code":1,"date":"2023-10-24 18:13:10","doi":"10.21203/rs.3.rs-3474127/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":"eb45870b-0954-4825-8c1d-a6f811a59c5e","owner":[],"postedDate":"February 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":44512453,"name":"Ophthalmology"}],"tags":[],"updatedAt":"2025-06-04T15:11:24+00:00","versionOfRecord":{"articleIdentity":"rs-3474127","link":"https://doi.org/10.62856/djcro.v7.48","journal":{"identity":"duke-journal-of-case-reports-in-ophthalmology","isVorOnly":true,"title":"Duke Journal of Case Reports in Ophthalmology"},"publishedOn":"2025-06-02 00:00:00","publishedOnDateReadable":"June 2nd, 2025"},"versionCreatedAt":"2025-02-05 09:18:51","video":"","vorDoi":"10.62856/djcro.v7.48","vorDoiUrl":"https://doi.org/10.62856/djcro.v7.48","workflowStages":[]},"version":"v2","identity":"rs-3474127","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3474127","identity":"rs-3474127","version":["v2"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}