Posterior Scleritis Following COVID-19 Vaccination or Infection Simulating Uveal Melanoma in 8 Consecutive Patients

Posterior Scleritis Following COVID-19 Vaccination or Infection Simulating Uveal Melanoma in 8 Consecutive Patients | 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 Article Posterior Scleritis Following COVID-19 Vaccination or Infection Simulating Uveal Melanoma in 8 Consecutive Patients Guy Negretti, Jennifer Zeiger, Elliot Cherkas, Carol Shields This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2464691/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 08 Jul, 2023 Read the published version in Eye → Version 1 posted 8 You are reading this latest preprint version Abstract Objectives To determine clinical features and outcomes of posterior scleritis masquerading as uveal melanoma following vaccination against COVID-19 and/or COVID-19 infection. Subjects/Methods: All patients with posterior scleritis referred to our service to rule out intraocular tumor between February 2021 and June 2022, who previously had COVID-19 vaccination and/or infection (n = 8). A retrospective detailed review of patient charts and imaging was carried out. Results Previous COVID-19 vaccination was documented in 6 patients (75%) and previous COVID-19 infection and vaccination in 2 patients (25%). Demographic features included mean age of 59 years (median 68, range 5–86 years), white race (n = 7, 87%), and male sex (n = 5, 63%). Mean visual acuity at presentation was 0.24 LogMAR (median 0.18, range 0.0-0.70). The main presenting symptom was blurred vision with pain (n = 5, 63%). Features that suggested scleritis and not uveal melanoma included pain (n = 6, 75%), anterior scleritis (n = 3, 38%), disc edema (n = 1, 13%), choroidal detachment (n = 3, 38%), choroidal folds (n = 3, 38%), diffusely thickened scleral wall on ultrasonography (n = 2, 25%), Tenon’s edema (n = 5, 63%), and scleral nodule with medium/high internal reflectivity on ultrasonography (n = 4, 50%). Follow-up information at mean of 2 months (range 0.25-7 months) revealed visual acuity at date last seen was mean 0.30 LogMAR (median 0.29, range 0.0-0.54). By 2 months, resolution of “tumor” was noted in 5/6 (83%) patients with follow-up. Conclusions Posterior scleritis following COVID-19 vaccination and/or infection can masquerade as choroidal melanoma. At 2 months duration, partial or complete resolution of features with minimal visual consequence was noted. Biological sciences/Immunology/Infectious diseases/Viral infection Biological sciences/Cancer/Eye cancer Biological sciences/Immunology/Inflammation Uvea Melanoma COVID-19 Sclera Scleritis Oncology Figures Figure 1 Figure 2 Introduction Choroidal melanoma is an uncommon malignancy with a mean age-adjusted incidence of 5 per million in the United States of America (USA). 1 The incidence of scleritis in the USA is reported to range from 1.6 per 100,000 person-years to 5.5 per 100,000 person-years. 2 – 6 The specific incidence of posterior scleritis is likely lower as it has been documented to represent approximately 4% of all scleritis cases. 6 Posterior scleritis is characterized by inflammation of the posterior scleral wall which can then affect surrounding ocular structures causing optic nerve edema, exudative retinal detachment, cystoid macular edema, choroidal detachment, choroidal folds, and Tenon’s edema. These findings can be mistaken for choroidal melanoma. Of the ophthalmic conditions misdiagnosed as choroidal melanoma (pseudomelanoma), posterior scleritis is rarely seen. 7 , 8 In a large series of 1,739 patients with pseudomelanoma from a tertiary ocular oncology service between 1978 and 2003, posterior scleritis was found to represent < 1% of cases. 7 COVID-19 vaccination and infection have been linked to several systemic autoimmune conditions including cerebral venous thrombosis, immune thrombocytopenia, and acute myocarditis. 9 – 11 There is emerging evidence that COVID-19 vaccination or infection could lead to inflammatory eye conditions, although the risk appears to be low with only a few cases of COVID-19 vaccine-associated uveitis reported in the peer-reviewed literature to date (however this might be due to under-reporting bias). 12 – 18 Inflammatory eye conditions linked to COVID-19 vaccination appear to be self-limiting and with minimal visual impact and reports of posterior scleritis following COVID-19 vaccination are exquisitely rare. 19 We experienced a rise in referrals to our ocular oncology service for possible intraocular tumor that proved to be posterior scleritis during the COVID-19 pandemic. Herein, we review our experience and describe the clinical features and outcomes of posterior scleritis “pseudomelanoma” following COVID-19 vaccination or infection. Methods The medical records of the Ocular Oncology Service at Wills Eye Hospital, Philadelphia, USA, were retrospectively reviewed for patients with a diagnosis of posterior scleritis referred for possible uveal melanoma between February 14th, 2021 and June 21st, 2022, who had previously had COVID-19 vaccination and/or infection. This study was approved by the Institutional Review Board of Wills Eye Hospital (IRB number: 2022 − 126), adhered to the tenets of the Declaration of Helsinki, and complied with the Health Insurance Portability and Accountability Act. Informed consent was obtained from all patients for inclusion in the study. The diagnosis of posterior scleritis was established on the Ocular Oncology Service by an ocular oncologist using detailed history-taking, slit lamp biomicroscopy, indirect ophthalmoscopy, and multimodal ophthalmic imaging, including wide-angle fundus photography, ultrasonography, fundus autofluorescence, optical coherence tomography (OCT), fluorescein angiography, and indocyanine green angiography, when necessary. Data was collected from each patient chart regarding demographics, COVID-19 vaccination or infection status, clinical features at initial presentation, and outcomes. Demographic data included patient age, race, sex, affected eye, and history/treatment of any autoimmune condition/ocular inflammation. Data on previous COVID-19 vaccination or infection included date of any vaccinations or infections, brand of COVID-19 vaccination (Pfizer Inc., Moderna Inc., Johnson and Johnson Ltd.), and systemic symptoms following each vaccination. Clinical data at initial examination included best corrected visual acuity (VA), intraocular pressure, and presence/absence of pain, anterior scleritis, optic nerve edema, exudative retinal detachment, retinal vasculitis, cystoid macular edema, choroidal detachment, choroidal folds, and cystoid macular edema. Data on B-scan ultrasonography included the presence/absence of a diffusely thickened eye wall, Tenon’s edema, and scleral nodularity. Outcomes data included date last seen visual acuity, change in visual acuity over time, and resolution of scleritis features including pain, optic nerve edema, exudative retinal detachment, choroidal detachment, choroidal folds, cystoid macular edema, scleral thickening, Tenon’s edema, and scleral nodularity. Results There were 8 patients diagnosed with posterior scleritis during the study period with 6 (75%) following COVID-19 vaccination (Fig. 1 ) and 2 (25%) following COVID-19 infection and vaccination (Fig. 2 ). Demographic features of the patients and details of COVID-19 vaccinations/infections are shown in Table 1. The mean patient age at presentation was 59 years (median 69 years, range 5–86 years) and the right eye was affected in 5 (63%) patients and the left in 3 (37%). There was predominance of white race (n = 7, 87%). By history, the mean interval from last COVID-19 vaccination to the onset of eye symptoms was 132 days (median 159 days, range 31–235 days) and the mean interval from COVID-19 infection to the onset of eye symptoms was 14 days (median 14 days, range 7–21 days). Patients were referred to the ocular oncology service by a retina specialist (n = 7, 88%) or pediatric ophthalmologist (n = 1, 12%) with a referring diagnosis of possible choroidal melanoma (n = 6, 75%), retinoblastoma (n = 1, 12%), or choroidal nevus (n = 1, 12%). No patients had a previous history of ocular inflammation. The clinical features of patients at the date first seen are shown in Table 2. The mean visual acuity at presentation was 0.24 LogMAR (median 0.18, range 0.0-0.70) (Snellen equivalent mean 20/34, median 20/30, range 20/20–20/100). The mean intraocular pressure was 15 mmHg (median 16 mmHg, range 8–18 mmHg). The main presenting symptoms were blurred vision (n = 6, 75%), and pain (n = 6, 75%). There was no patient who displayed anterior chamber cells, vitreous cells, retinal vasculitis, or cystoid macular edema. Discrete scleral nodularity was identified on ultrasonography in 4 (50%) patients, with medium (n = 2, 25%) or high (n = 2, 25%) internal echogenicity, mean thickness of 2.4 mm (median 1.9 mm, range 1.9–3.3 mm), and dome-shaped (n = 4, 50%) with a base to maximum elevation ratio less than 7:1. Outcomes for 6 patients with follow-up are shown in Table 3. Mean follow-up was 2 months (median 1 month, range 0.25-7 months). Mean visual acuity at date last seen was 0.30 LogMAR (median 0.29, range 0.0-0.54) (Snellen equivalent mean 20/40, median 20/40, range 20/20–20/70). At 2 months follow up, resolution of “tumor” was noted in 5/6 (83%) patients and related findings showing partial or complete resolution included ocular pain (4/4, 100%), optic nerve edema (1/1, 100%), exudative retinal detachment (6/6, 100%), and on ultrasonography thickened scleral wall (2/2, 100%), Tenon’s edema (5/5, 100%) and scleral nodularity (3/3, 100%). Mean time to resolution of pain was 2 months (median 1 month, range 0.25-6 months), optic nerve edema 2 months, exudative retinal detachment 2 months (median 1 month, range 0.25-6 months), diffusely thickened scleral wall 1 month (median 1 month, range 0.25-1 month), Tenon’s edema 2 months (median 1 month, range 0.25-6 months), and discrete scleral nodularity 1 month (median 1 month, range 1–1 month). Discussion Viruses have long been implicated in the development of autoimmune conditions. 20 The proposed immunological mechanism through which a virus could lead to autoimmunity is through molecular mimicry or bystander T-cell activation. 20 There is growing evidence that COVID-19 infection causes dysregulation of the immune system and has been linked to several systemic autoimmune conditions, particularly vasculitis and inflammatory arthritis. 20 Idiopathic inflammatory myopathies, systemic lupus erythematosus, and sarcoidosis have also all been linked to COVID-19 infection. 20 Ocular manifestations of COVID-19 infection, particularly anterior segment complications, are relatively common. A meta-analysis of 2,347 confirmed COVID-19 infection cases showed that 11% of infected patients displayed ocular surface manifestations. 21 Ocular pain (31%), discharge (19%), redness (11%), and follicular conjunctivitis (8%) were the main findings, and COVID-19 RNA was detected in 4% of ocular specimens from these patients. 21 Posterior segment manifestations of infection, based on case reports alone, mainly relate to the pro-thrombotic state that can arise from COVID-19 infection and manifest with retinal vascular occlusion, acute macular neuroretinopathy, and paracentral acute middle maculopathy. 22 Neuro-ophthalmic manifestations of COVID-19 infection include isolated cranial nerve palsies, Miller Fisher syndrome, nystagmus, and saccadic intrusions in association with either brainstem infarction or hemorrhagic acute necrotizing encephalopathy. 22 There are several case reports of episcleritis, anterior scleritis, and uveitis associated with COVID-19 infection, but no reported cases or series of posterior scleritis, as we document herein. 23 – 26 It has long been suspected that vaccinations can predispose to autoimmune conditions. 27 Inflammatory ocular conditions, particularly uveitis, have previously been described following vaccination. In the pre-COVID-19 era, Benage and Fraunfelder reviewed a series of 289 cases of vaccine-associated uveitis reported over a 26-year period. 28 The hepatitis B vaccine appeared as the leading offender in the past. 28 Proposed immunological mechanisms include molecular mimicry, delayed-type hypersensitivity with immune complex deposition, and immune responses generated against adjuvants within the vaccine. 28 COVID-19 vaccination has been linked to several systemic autoimmune conditions including cerebral venous thrombosis, immune thrombocytopenia, and acute myocarditis. 9 – 11 COVID-19 vaccination has been linked to autoimmune ocular complications but data from population-based pharmacovigilance surveillance systems suggest that the prevalence of vaccination-associated ocular adverse events are rare. 12 A multinational study from 40 centers over a 3-month period found 70 patients with ocular inflammatory events within 14 days of COVID-19 vaccination. 17 The most common events were anterior uveitis (n = 41, 59%), posterior uveitis (n = 9, 13%), and anterior scleritis (n = 7, 10%). 17 Singh et al reviewed the Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS) of 1,094 cases of COVID-19 vaccine-associated uveitis and found that most cases were reported after the Pfizer-BioNTech BNT162b2 vaccine (n = 853, 78%), after the first dose (n = 452, 41%), and within the first week (n = 591, 54%) following vaccination. 13 Despite this, the low crude reporting rate and observed-expected ratio suggested a low safety concern for vaccine-associated uveitis. 13 Several isolated case reports have linked COVID-19 vaccination to other autoimmune ocular complications including corneal graft rejection, optic neuropathies, herpetic eye disease, and Vogt-Kayanagi-Harada disease. 12 , 18 One case report has linked COVID-19 vaccination to posterior scleritis. 19 In this study, we review a series of 8 patients who presented with posterior scleritis masquerading as uveal melanoma following COVID-19 vaccination and/or COVID-19 infection. The mean interval from last COVID-19 vaccination to the onset of eye symptoms was 132 days (median 159 days, range 31–235 days) and the interval from onset of COVID-19 infection to the onset of eye symptoms was 14 days (median 14 days, range 7–21 days). By 2 months following presentation, most signs and symptoms had completely resolved except for one patient with persistent choroidal detachment and folds. The main limitation of this study is our inability to prove a causal link between vaccination against COVID-19 and/or COVID-19 infection and posterior scleritis. It was, however, the most obvious variable relative to the scleritis. A previous study on etiology of choroidal pseudomelanoma identified posterior scleritis in a few cases. 7 Another limitation is that two of our patients were lost to follow-up, likely returning to their local ophthalmologist as we reassured them of the lack of melanoma. Loss to follow-up is anticipated, especially in this condition that can resolve spontaneously over time and can be managed locally. In summary, we documented 8 cases of COVID-19-related posterior scleritis simulating uveal melanoma that followed vaccination and/or infection by the virus. With conservative management, the inflammation tended to be self-limiting with resolution over 2 months and with minimal visual consequences. Declarations Conflict of Interest No conflict of interest exists for any of the authors. Funding Support provided in part by the Moorfields Eye Charity (GN), TFC Frost Charitable Trust (GN) the Worshipful Company of Spectacle Makers Charity (GN), and the Eye Tumor Research Foundation, Philadelphia, PA (CLS). The funders had no role in the design and conduct of the study, in the collection, analysis and interpretation of the data, and in the preparation, review or approval of the manuscript References Singh AD, Turell ME, Topham AK. Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology . 2011;118:1881-5. Honik G, Wong IG, Gritz DC. Incidence and prevalence of episcleritis and scleritis in Northern California. Cornea . 2013;32:1562-6. Homayounfar G, Nardone N, Borkar DS, et al. Incidence of scleritis and episcleritis: results from the Pacific Ocular Inflammation Study. Am J Ophthalmol . 2013;156:752-8. Homayounfar G, Borkar DS, Tham VM, et al. Clinical characteristics of scleritis and episcleritis: results from the Pacific Ocular Inflammation Study. Ocul Immunol Inflamm . 2014;22:403-4. Zhang Y, Amin S, Lung KI, et al. Incidence, prevalence, and risk factors of infectious uveitis and scleritis in the United States: a claims-based analysis. PLoS One. 2020;15:e0237995. Xu TT, Reynolds MM, Hodge DO, et al. Epidemiology and clinical characteristics of episcleritis and scleritis in Olmsted County, Minnesota. Am J Ophthalmol . 2020;217:317-324. Shields CL, Manalac J, Das C, et al. Choroidal melanoma: clinical features, classification, and top 10 pseudomelanomas. Curr Opin Ophthalmol . 2014;25:177-85. Ghassemi F, Bazvand F, Hosseini SS. Pseudomelanoma at a referral center in Iran. J Ophthalmic Vis Res . 2014;9:50-3. Hippisley-Cox J, Patone M, Mei XW, et al. Risk of thrombocytopenia and thromboembolism after Covid-19 vaccination and SARS-CoV-2 positive testing: self-controlled case series study. BMJ . 2021;374:n1931. Diaz GA, Parsons GT, Gering SK, et al. Myocarditis and pericarditis after vaccination for COVID-19. JAMA . 2021;326:1210-1212. Thakur KT, Tamborska A, Wood GK, et al. Clinical review of cerebral venous thrombosis in the context of COVID-19 vaccinations: evaluation, management, and scientific questions. J Neurol Sci . 2021;427:117532. Wang MTM, Niederer RL, McGhee CNJ, et al. COVID-19 vaccination and the eye. Am J Ophthalmol . 2022;240:79-98. Singh RB, Singh Parmar UP, Kahale F, et al. Vaccine-associated uveitis following SARS-CoV-2 vaccination: a CDC-VAERS database analysis. [published online ahead of print, 2022 Aug 31]. Ophthalmology . 2022:S0161-6420(22)00672-8. Pichi F, Aljneibi S, Neri P, et al. Association of ocular adverse events with inactivated COVID-19 vaccination in patients in Abu Dhabi. JAMA Ophthalmol . 2021;139:1131-1135. Seah I, Agrawal R. Can the coronavirus disease 2019 (COVID-19) affect the eyes? A review of coronaviruses and ocular implications in humans and animals. Ocul Immunol Inflamm . 2020;28:391-395. Eleiwa T, Abdelrahman SN, ElSheikh RH, et al. Orbital inflammatory disease associated with COVID-19 infection. J AAPOS . 2021;25:232-234. Testi I, Brandão-de-Resende C, Agrawal R, et al. Ocular inflammatory events following COVID-19 vaccination: a multinational case series. J Ophthalmic Inflamm Infect . 2022;12:4. Ng XL, Betzler BK, Ng S, et al. The eye of the storm: COVID-19 vaccination and the eye. Ophthalmol Ther . 2022;11:81-100. Younus O, Mulla U. Posterior scleritis following COVID-19 vaccination: a case report. Ocul Immunol Inflamm . 2022:1-3. Gracia-Ramos AE, Martin-Nares E, Hernández-Molina G. New onset of autoimmune diseases following COVID-19 diagnosis. Cells . 2021;10:3592. Aggarwal K, Agarwal A, Jaiswal N, et al. Ocular surface manifestations of coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis. PLoS One . 2020;15:e0241661 Sen M, Honavar SG, Sharma N, et al. COVID-19 and eye: a review of ophthalmic manifestations of COVID-19. Indian J Ophthalmol . 2021;69:488-509. Adenwala A, Shetty R, D'Souza S, et al. Nodular scleritis-a rare presentation of COVID-19& variation with testing. Am J Ophthalmol Case Rep . 2022;25:101396. Islam M, Chou M, Braithwaite T, et al. Bilateral anterior non-necrotising scleritis, anterior uveitis, and unilateral facial nerve palsy in paediatric inflammatory multisystem syndrome temporally associated with COVID-19. Lancet Rheumatol . 2021;3:e818 Feizi S, Meshksar A, Naderi A, et al. Anterior scleritis manifesting after coronavirus disease 2019: a report of two cases. Cornea . 2021;40:1204-1206. Méndez Mangana C, Barraquer Kargacin A, Barraquer RI. Episcleritis as an ocular manifestation in a patient with COVID-19. Acta Ophthalmol . 2020;98:e1056-e1057. Guimarães LE, Baker B, Perricone C, et al. Vaccines, adjuvants and autoimmunity. Pharmacol Res . 2015;100:190-209. Benage M, Fraunfelder FW. Vaccine-associated uveitis. Mo Med . 2016;113:48-52 Tables Tables 1 to 3 are available in the Supplementary Files section. Additional Declarations There is no conflict of interest Supplementary Files 230110table1posteriorscleritisandcovid19.jpg Table 1 230110table2posteriorscleritisandcovid19.jpg Table 2 230110table3posteriorscleritisandcovid19.jpg Table 3 Cite Share Download PDF Status: Published Journal Publication published 08 Jul, 2023 Read the published version in Eye → Version 1 posted Editorial decision: revise 13 Jun, 2023 Reviewer # 2 agreed at journal 28 Apr, 2023 Review # 1 received at journal 12 Apr, 2023 Reviewer # 1 agreed at journal 04 Apr, 2023 Reviewers invited by journal 06 Feb, 2023 Editor assigned by journal 01 Feb, 2023 Submission checks completed at journal 12 Jan, 2023 First submitted to journal 10 Jan, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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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-2464691","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":173863802,"identity":"424b9880-8e94-4d7b-8eb3-b2ca02b36c7f","order_by":0,"name":"Guy Negretti","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Guy","middleName":"","lastName":"Negretti","suffix":""},{"id":173863803,"identity":"c5ca7a5c-b902-4cd3-a7e1-36a710408024","order_by":1,"name":"Jennifer Zeiger","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jennifer","middleName":"","lastName":"Zeiger","suffix":""},{"id":173863804,"identity":"55731887-1779-44e0-8e66-3a2971cf6a29","order_by":2,"name":"Elliot Cherkas","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Elliot","middleName":"","lastName":"Cherkas","suffix":""},{"id":173863805,"identity":"0c7a0861-6bf6-4d82-a5b7-b2211870df0c","order_by":3,"name":"Carol Shields","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIie3PMUsDMRTA8RcepMuzWXNU8CtECoKg3Fe5Q6iLXTsfHNwtra46+SEKnZWsugtxOJebU7oUyWDi5tC7cxPMfwg8eD8eAYjF/moNPBGMQIH1Ax8NIVkgCIrdB4IDCQSCFKY+IurXjyZz78cCcb27+NycjBGY3d4cJvLleqryqqWk5IvJ/NacVgiYPGwOEwUzLvNCk9J0hvOlYZ5wPOoiouUyc5pSTdPd+dKk/UT6Kxn3V5DUBPYm7yXyrUX/F01S80WyKsxVhazs/Iu4m7HGOp2KulzbvTOXj3X5bLcd5Ges+n6Lofsh95vlWCwW+y99AWSsS9iN2DFAAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-3288-3632","institution":"Wills Eye Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Carol","middleName":"","lastName":"Shields","suffix":""}],"badges":[],"createdAt":"2023-01-10 21:40:57","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2464691/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2464691/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41433-023-02656-z","type":"published","date":"2023-07-08T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":32667703,"identity":"e1fb151c-43fe-4a27-9c98-ec643d63b758","added_by":"auto","created_at":"2023-02-08 20:04:08","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":777275,"visible":true,"origin":"","legend":"\u003cp\u003ePosterior scleritis and choroidal effusion appearing 24 weeks following COVID-19 vaccination. (A) Fundus photography of the left eye (OS) revealed a superonasal choroidal effusion with “high water mark” and multiple hyperautofluorescent choroidal folds (B). (C) By optical coherence tomography (OCT) (vertical cut through fovea), intraretinal and shallow subretinal fluid with prominent choroidal folds were observed. (D) Ultrasonography revealed thickened choroidal detachment with episcleral Tenon’s edema (asterisk), suggestive of scleritis and (E) at 4 weeks later, ultrasonography showed near-complete resolution of choroidal effusion and Tenon’s edema.\u003c/p\u003e","description":"","filename":"figure1posteriorscleritisandcovid19.png","url":"https://assets-eu.researchsquare.com/files/rs-2464691/v1/ec703c0b28eac652acbd6e6a.png"},{"id":32667702,"identity":"c00d1f3f-f5e4-464a-832a-0a0355a81751","added_by":"auto","created_at":"2023-02-08 20:04:08","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":858419,"visible":true,"origin":"","legend":"\u003cp\u003ePosterior scleritis with choroidal effusion appearing 3 weeks after testing positive for COVID-19 infection. (A) Fundus photography of the left eye (OS) revealed choroidal effusion inferonasally with a “high water mark” posteriorly suggesting partial resolution of fluid. (B) Ultrasonography confirmed the choroidal effusion at 2.6 mm in thickness and with minimal scleritis-related Tenon’s edema (echolucency).\u003c/p\u003e","description":"","filename":"figure2posteriorscleritisandcovid19.png","url":"https://assets-eu.researchsquare.com/files/rs-2464691/v1/914e490dd3aae137ef3f9c90.png"},{"id":39746108,"identity":"18678f6b-77e8-4a3a-8e0c-a171b29ffec3","added_by":"auto","created_at":"2023-07-09 07:07:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2109935,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2464691/v1/65bd88fd-f19f-4380-9fdf-04a4c2cd7688.pdf"},{"id":32668392,"identity":"7f1ec696-9f5f-40c6-b635-19e4b66e133f","added_by":"auto","created_at":"2023-02-08 20:20:08","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":844345,"visible":true,"origin":"","legend":"\u003cp\u003eTable 1\u003c/p\u003e","description":"","filename":"230110table1posteriorscleritisandcovid19.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2464691/v1/15377fa86e9cfb668244ae7b.jpg"},{"id":32667706,"identity":"9504ebdb-3334-4c62-b574-59d70da3b77b","added_by":"auto","created_at":"2023-02-08 20:04:08","extension":"jpg","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":658246,"visible":true,"origin":"","legend":"\u003cp\u003eTable 2\u003c/p\u003e","description":"","filename":"230110table2posteriorscleritisandcovid19.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2464691/v1/c12472f6d31b3757bf73751e.jpg"},{"id":32667931,"identity":"a4b2df72-ac8c-4971-861d-a70f446a5e9b","added_by":"auto","created_at":"2023-02-08 20:12:08","extension":"jpg","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":829995,"visible":true,"origin":"","legend":"Table 3","description":"","filename":"230110table3posteriorscleritisandcovid19.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2464691/v1/88dd6530bc885c14f7fe6313.jpg"}],"financialInterests":"There is no conflict of interest","formattedTitle":"Posterior Scleritis Following COVID-19 Vaccination or Infection Simulating Uveal Melanoma in 8 Consecutive Patients","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChoroidal melanoma is an uncommon malignancy with a mean age-adjusted incidence of 5 per million in the United States of America (USA).\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e The incidence of scleritis in the USA is reported to range from 1.6 per 100,000 person-years to 5.5 per 100,000 person-years.\u003csup\u003e\u003cspan additionalcitationids=\"CR3 CR4 CR5\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e–\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e The specific incidence of posterior scleritis is likely lower as it has been documented to represent approximately 4% of all scleritis cases.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Posterior scleritis is characterized by inflammation of the posterior scleral wall which can then affect surrounding ocular structures causing optic nerve edema, exudative retinal detachment, cystoid macular edema, choroidal detachment, choroidal folds, and Tenon’s edema. These findings can be mistaken for choroidal melanoma. Of the ophthalmic conditions misdiagnosed as choroidal melanoma (pseudomelanoma), posterior scleritis is rarely seen.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e In a large series of 1,739 patients with pseudomelanoma from a tertiary ocular oncology service between 1978 and 2003, posterior scleritis was found to represent \u0026lt; 1% of cases.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eCOVID-19 vaccination and infection have been linked to several systemic autoimmune conditions including cerebral venous thrombosis, immune thrombocytopenia, and acute myocarditis.\u003csup\u003e\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e–\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e There is emerging evidence that COVID-19 vaccination or infection could lead to inflammatory eye conditions, although the risk appears to be low with only a few cases of COVID-19 vaccine-associated uveitis reported in the peer-reviewed literature to date (however this might be due to under-reporting bias).\u003csup\u003e\u003cspan additionalcitationids=\"CR13 CR14 CR15 CR16 CR17\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e–\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Inflammatory eye conditions linked to COVID-19 vaccination appear to be self-limiting and with minimal visual impact and reports of posterior scleritis following COVID-19 vaccination are exquisitely rare.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWe experienced a rise in referrals to our ocular oncology service for possible intraocular tumor that proved to be posterior scleritis during the COVID-19 pandemic. Herein, we review our experience and describe the clinical features and outcomes of posterior scleritis “pseudomelanoma” following COVID-19 vaccination or infection.\u003c/p\u003e "},{"header":"Methods","content":"\u003cp\u003eThe medical records of the Ocular Oncology Service at Wills Eye Hospital, Philadelphia, USA, were retrospectively reviewed for patients with a diagnosis of posterior scleritis referred for possible uveal melanoma between February 14th, 2021 and June 21st, 2022, who had previously had COVID-19 vaccination and/or infection. This study was approved by the Institutional Review Board of Wills Eye Hospital (IRB number: 2022 − 126), adhered to the tenets of the Declaration of Helsinki, and complied with the Health Insurance Portability and Accountability Act. Informed consent was obtained from all patients for inclusion in the study.\u003c/p\u003e\u003cp\u003eThe diagnosis of posterior scleritis was established on the Ocular Oncology Service by an ocular oncologist using detailed history-taking, slit lamp biomicroscopy, indirect ophthalmoscopy, and multimodal ophthalmic imaging, including wide-angle fundus photography, ultrasonography, fundus autofluorescence, optical coherence tomography (OCT), fluorescein angiography, and indocyanine green angiography, when necessary.\u003c/p\u003e\u003cp\u003eData was collected from each patient chart regarding demographics, COVID-19 vaccination or infection status, clinical features at initial presentation, and outcomes. Demographic data included patient age, race, sex, affected eye, and history/treatment of any autoimmune condition/ocular inflammation. Data on previous COVID-19 vaccination or infection included date of any vaccinations or infections, brand of COVID-19 vaccination (Pfizer Inc., Moderna Inc., Johnson and Johnson Ltd.), and systemic symptoms following each vaccination. Clinical data at initial examination included best corrected visual acuity (VA), intraocular pressure, and presence/absence of pain, anterior scleritis, optic nerve edema, exudative retinal detachment, retinal vasculitis, cystoid macular edema, choroidal detachment, choroidal folds, and cystoid macular edema. Data on B-scan ultrasonography included the presence/absence of a diffusely thickened eye wall, Tenon’s edema, and scleral nodularity. Outcomes data included date last seen visual acuity, change in visual acuity over time, and resolution of scleritis features including pain, optic nerve edema, exudative retinal detachment, choroidal detachment, choroidal folds, cystoid macular edema, scleral thickening, Tenon’s edema, and scleral nodularity.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThere were 8 patients diagnosed with posterior scleritis during the study period with 6 (75%) following COVID-19 vaccination (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) and 2 (25%) following COVID-19 infection and vaccination (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Demographic features of the patients and details of COVID-19 vaccinations/infections are shown in Table\u0026nbsp;1. The mean patient age at presentation was 59 years (median 69 years, range 5\u0026ndash;86 years) and the right eye was affected in 5 (63%) patients and the left in 3 (37%). There was predominance of white race (n\u0026thinsp;=\u0026thinsp;7, 87%). By history, the mean interval from last COVID-19 vaccination to the onset of eye symptoms was 132 days (median 159 days, range 31\u0026ndash;235 days) and the mean interval from COVID-19 infection to the onset of eye symptoms was 14 days (median 14 days, range 7\u0026ndash;21 days). Patients were referred to the ocular oncology service by a retina specialist (n\u0026thinsp;=\u0026thinsp;7, 88%) or pediatric ophthalmologist (n\u0026thinsp;=\u0026thinsp;1, 12%) with a referring diagnosis of possible choroidal melanoma (n\u0026thinsp;=\u0026thinsp;6, 75%), retinoblastoma (n\u0026thinsp;=\u0026thinsp;1, 12%), or choroidal nevus (n\u0026thinsp;=\u0026thinsp;1, 12%). No patients had a previous history of ocular inflammation.\u003c/p\u003e \u003cp\u003eThe clinical features of patients at the date first seen are shown in Table\u0026nbsp;2. The mean visual acuity at presentation was 0.24 LogMAR (median 0.18, range 0.0-0.70) (Snellen equivalent mean 20/34, median 20/30, range 20/20\u0026ndash;20/100). The mean intraocular pressure was 15 mmHg (median 16 mmHg, range 8\u0026ndash;18 mmHg). The main presenting symptoms were blurred vision (n\u0026thinsp;=\u0026thinsp;6, 75%), and pain (n\u0026thinsp;=\u0026thinsp;6, 75%). There was no patient who displayed anterior chamber cells, vitreous cells, retinal vasculitis, or cystoid macular edema. Discrete scleral nodularity was identified on ultrasonography in 4 (50%) patients, with medium (n\u0026thinsp;=\u0026thinsp;2, 25%) or high (n\u0026thinsp;=\u0026thinsp;2, 25%) internal echogenicity, mean thickness of 2.4 mm (median 1.9 mm, range 1.9\u0026ndash;3.3 mm), and dome-shaped (n\u0026thinsp;=\u0026thinsp;4, 50%) with a base to maximum elevation ratio less than 7:1.\u003c/p\u003e \u003cp\u003eOutcomes for 6 patients with follow-up are shown in Table\u0026nbsp;3. Mean follow-up was 2 months (median 1 month, range 0.25-7 months). Mean visual acuity at date last seen was 0.30 LogMAR (median 0.29, range 0.0-0.54) (Snellen equivalent mean 20/40, median 20/40, range 20/20\u0026ndash;20/70). At 2 months follow up, resolution of \u0026ldquo;tumor\u0026rdquo; was noted in 5/6 (83%) patients and related findings showing partial or complete resolution included ocular pain (4/4, 100%), optic nerve edema (1/1, 100%), exudative retinal detachment (6/6, 100%), and on ultrasonography thickened scleral wall (2/2, 100%), Tenon\u0026rsquo;s edema (5/5, 100%) and scleral nodularity (3/3, 100%). Mean time to resolution of pain was 2 months (median 1 month, range 0.25-6 months), optic nerve edema 2 months, exudative retinal detachment 2 months (median 1 month, range 0.25-6 months), diffusely thickened scleral wall 1 month (median 1 month, range 0.25-1 month), Tenon\u0026rsquo;s edema 2 months (median 1 month, range 0.25-6 months), and discrete scleral nodularity 1 month (median 1 month, range 1\u0026ndash;1 month).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eViruses have long been implicated in the development of autoimmune conditions.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e The proposed immunological mechanism through which a virus could lead to autoimmunity is through molecular mimicry or bystander T-cell activation.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e There is growing evidence that COVID-19 infection causes dysregulation of the immune system and has been linked to several systemic autoimmune conditions, particularly vasculitis and inflammatory arthritis.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e Idiopathic inflammatory myopathies, systemic lupus erythematosus, and sarcoidosis have also all been linked to COVID-19 infection.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e Ocular manifestations of COVID-19 infection, particularly anterior segment complications, are relatively common. A meta-analysis of 2,347 confirmed COVID-19 infection cases showed that 11% of infected patients displayed ocular surface manifestations.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e Ocular pain (31%), discharge (19%), redness (11%), and follicular conjunctivitis (8%) were the main findings, and COVID-19 RNA was detected in 4% of ocular specimens from these patients.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e Posterior segment manifestations of infection, based on case reports alone, mainly relate to the pro-thrombotic state that can arise from COVID-19 infection and manifest with retinal vascular occlusion, acute macular neuroretinopathy, and paracentral acute middle maculopathy.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e Neuro-ophthalmic manifestations of COVID-19 infection include isolated cranial nerve palsies, Miller Fisher syndrome, nystagmus, and saccadic intrusions in association with either brainstem infarction or hemorrhagic acute necrotizing encephalopathy.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e There are several case reports of episcleritis, anterior scleritis, and uveitis associated with COVID-19 infection, but no reported cases or series of posterior scleritis, as we document herein.\u003csup\u003e\u003cspan additionalcitationids=\"CR24 CR25\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIt has long been suspected that vaccinations can predispose to autoimmune conditions.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e Inflammatory ocular conditions, particularly uveitis, have previously been described following vaccination. In the pre-COVID-19 era, Benage and Fraunfelder reviewed a series of 289 cases of vaccine-associated uveitis reported over a 26-year period.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e The hepatitis B vaccine appeared as the leading offender in the past.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e Proposed immunological mechanisms include molecular mimicry, delayed-type hypersensitivity with immune complex deposition, and immune responses generated against adjuvants within the vaccine.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eCOVID-19 vaccination has been linked to several systemic autoimmune conditions including cerebral venous thrombosis, immune thrombocytopenia, and acute myocarditis.\u003csup\u003e\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e COVID-19 vaccination has been linked to autoimmune ocular complications but data from population-based pharmacovigilance surveillance systems suggest that the prevalence of vaccination-associated ocular adverse events are rare.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e A multinational study from 40 centers over a 3-month period found 70 patients with ocular inflammatory events within 14 days of COVID-19 vaccination.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e The most common events were anterior uveitis (n\u0026thinsp;=\u0026thinsp;41, 59%), posterior uveitis (n\u0026thinsp;=\u0026thinsp;9, 13%), and anterior scleritis (n\u0026thinsp;=\u0026thinsp;7, 10%).\u003csup\u003e17\u003c/sup\u003e Singh \u003cem\u003eet al\u003c/em\u003e reviewed the Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS) of 1,094 cases of COVID-19 vaccine-associated uveitis and found that most cases were reported after the Pfizer-BioNTech BNT162b2 vaccine (n\u0026thinsp;=\u0026thinsp;853, 78%), after the first dose (n\u0026thinsp;=\u0026thinsp;452, 41%), and within the first week (n\u0026thinsp;=\u0026thinsp;591, 54%) following vaccination.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e Despite this, the low crude reporting rate and observed-expected ratio suggested a low safety concern for vaccine-associated uveitis.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e Several isolated case reports have linked COVID-19 vaccination to other autoimmune ocular complications including corneal graft rejection, optic neuropathies, herpetic eye disease, and Vogt-Kayanagi-Harada disease.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e One case report has linked COVID-19 vaccination to posterior scleritis.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn this study, we review a series of 8 patients who presented with posterior scleritis masquerading as uveal melanoma following COVID-19 vaccination and/or COVID-19 infection. The mean interval from last COVID-19 vaccination to the onset of eye symptoms was 132 days (median 159 days, range 31\u0026ndash;235 days) and the interval from onset of COVID-19 infection to the onset of eye symptoms was 14 days (median 14 days, range 7\u0026ndash;21 days). By 2 months following presentation, most signs and symptoms had completely resolved except for one patient with persistent choroidal detachment and folds.\u003c/p\u003e \u003cp\u003eThe main limitation of this study is our inability to prove a causal link between vaccination against COVID-19 and/or COVID-19 infection and posterior scleritis. It was, however, the most obvious variable relative to the scleritis. A previous study on etiology of choroidal pseudomelanoma identified posterior scleritis in a few cases.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Another limitation is that two of our patients were lost to follow-up, likely returning to their local ophthalmologist as we reassured them of the lack of melanoma. Loss to follow-up is anticipated, especially in this condition that can resolve spontaneously over time and can be managed locally.\u003c/p\u003e \u003cp\u003eIn summary, we documented 8 cases of COVID-19-related posterior scleritis simulating uveal melanoma that followed vaccination and/or infection by the virus. With conservative management, the inflammation tended to be self-limiting with resolution over 2 months and with minimal visual consequences.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo conflict of interest exists for any of the authors.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSupport provided in part by the Moorfields Eye Charity (GN), TFC Frost Charitable Trust (GN) the Worshipful Company of Spectacle Makers Charity (GN), and the Eye Tumor Research Foundation, Philadelphia, PA (CLS). The funders had no role in the design and conduct of the study, in the collection, analysis and interpretation of the data, and in the preparation, review or approval of the manuscript\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSingh AD, Turell ME, Topham AK. Uveal melanoma: trends in incidence, treatment, and survival. \u003cem\u003eOphthalmology\u003c/em\u003e. 2011;118:1881-5.\u003c/li\u003e\n\u003cli\u003eHonik G, Wong IG, Gritz DC. Incidence and prevalence of episcleritis and scleritis in Northern California. \u003cem\u003eCornea\u003c/em\u003e. 2013;32:1562-6.\u003c/li\u003e\n\u003cli\u003eHomayounfar G, Nardone N, Borkar DS, et al. Incidence of scleritis and episcleritis: results from the Pacific Ocular Inflammation Study. \u003cem\u003eAm J Ophthalmol\u003c/em\u003e. 2013;156:752-8.\u003c/li\u003e\n\u003cli\u003eHomayounfar G, Borkar DS, Tham VM, et al. Clinical characteristics of scleritis and episcleritis: results from the Pacific Ocular Inflammation Study. \u003cem\u003eOcul Immunol Inflamm\u003c/em\u003e. 2014;22:403-4.\u003c/li\u003e\n\u003cli\u003eZhang Y, Amin S, Lung KI, et al. Incidence, prevalence, and risk factors of infectious uveitis and scleritis in the United States: a claims-based analysis. 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Myocarditis and pericarditis after vaccination for COVID-19. \u003cem\u003eJAMA\u003c/em\u003e. 2021;326:1210-1212. \u003c/li\u003e\n\u003cli\u003eThakur KT, Tamborska A, Wood GK, et al. Clinical review of cerebral venous thrombosis in the context of COVID-19 vaccinations: evaluation, management, and scientific questions. \u003cem\u003eJ Neurol Sci\u003c/em\u003e. 2021;427:117532. \u003c/li\u003e\n\u003cli\u003eWang MTM, Niederer RL, McGhee CNJ, et al. COVID-19 vaccination and the eye. \u003cem\u003eAm J Ophthalmol\u003c/em\u003e. 2022;240:79-98.\u003c/li\u003e\n\u003cli\u003eSingh RB, Singh Parmar UP, Kahale F, et al. Vaccine-associated uveitis following SARS-CoV-2 vaccination: a CDC-VAERS database analysis. [published online ahead of print, 2022 Aug 31]. \u003cem\u003eOphthalmology\u003c/em\u003e. 2022:S0161-6420(22)00672-8.\u003c/li\u003e\n\u003cli\u003ePichi F, Aljneibi S, Neri P, et al. Association of ocular adverse events with inactivated COVID-19 vaccination in patients in Abu Dhabi. \u003cem\u003eJAMA Ophthalmol\u003c/em\u003e. 2021;139:1131-1135. \u003c/li\u003e\n\u003cli\u003eSeah I, Agrawal R. Can the coronavirus disease 2019 (COVID-19) affect the eyes? A review of coronaviruses and ocular implications in humans and animals. \u003cem\u003eOcul Immunol Inflamm\u003c/em\u003e. 2020;28:391-395.\u003c/li\u003e\n\u003cli\u003eEleiwa T, Abdelrahman SN, ElSheikh RH, et al. Orbital inflammatory disease associated with COVID-19 infection. \u003cem\u003eJ AAPOS\u003c/em\u003e. 2021;25:232-234.\u003c/li\u003e\n\u003cli\u003eTesti I, Brand\u0026atilde;o-de-Resende C, Agrawal R, et al. Ocular inflammatory events following COVID-19 vaccination: a multinational case series. \u003cem\u003eJ Ophthalmic Inflamm Infect\u003c/em\u003e. 2022;12:4.\u003c/li\u003e\n\u003cli\u003eNg XL, Betzler BK, Ng S, et al. The eye of the storm: COVID-19 vaccination and the eye. \u003cem\u003eOphthalmol Ther\u003c/em\u003e. 2022;11:81-100.\u003c/li\u003e\n\u003cli\u003eYounus O, Mulla U. Posterior scleritis following COVID-19 vaccination: a case report. \u003cem\u003eOcul Immunol Inflamm\u003c/em\u003e. 2022:1-3.\u003c/li\u003e\n\u003cli\u003eGracia-Ramos AE, Martin-Nares E, Hern\u0026aacute;ndez-Molina G. New onset of autoimmune diseases following COVID-19 diagnosis. \u003cem\u003eCells\u003c/em\u003e. 2021;10:3592. \u003c/li\u003e\n\u003cli\u003eAggarwal K, Agarwal A, Jaiswal N, et al. Ocular surface manifestations of coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis. \u003cem\u003ePLoS One\u003c/em\u003e. 2020;15:e0241661\u003c/li\u003e\n\u003cli\u003eSen M, Honavar SG, Sharma N, et al. COVID-19 and eye: a review of ophthalmic manifestations of COVID-19. \u003cem\u003eIndian J Ophthalmol\u003c/em\u003e. 2021;69:488-509.\u003c/li\u003e\n\u003cli\u003eAdenwala A, Shetty R, D\u0026apos;Souza S, et al. Nodular scleritis-a rare presentation of COVID-19\u0026amp; variation with testing. \u003cem\u003eAm J Ophthalmol Case Rep\u003c/em\u003e. 2022;25:101396.\u003c/li\u003e\n\u003cli\u003eIslam M, Chou M, Braithwaite T, et al. Bilateral anterior non-necrotising scleritis, anterior uveitis, and unilateral facial nerve palsy in paediatric inflammatory multisystem syndrome temporally associated with COVID-19. \u003cem\u003eLancet Rheumatol\u003c/em\u003e. 2021;3:e818\u003c/li\u003e\n\u003cli\u003eFeizi S, Meshksar A, Naderi A, et al. Anterior scleritis manifesting after coronavirus disease 2019: a report of two cases. \u003cem\u003eCornea\u003c/em\u003e. 2021;40:1204-1206. \u003c/li\u003e\n\u003cli\u003eM\u0026eacute;ndez Mangana C, Barraquer Kargacin A, Barraquer RI. Episcleritis as an ocular manifestation in a patient with COVID-19. \u003cem\u003eActa Ophthalmol\u003c/em\u003e. 2020;98:e1056-e1057. \u003c/li\u003e\n\u003cli\u003eGuimar\u0026atilde;es LE, Baker B, Perricone C, et al. Vaccines, adjuvants and autoimmunity. \u003cem\u003ePharmacol Res\u003c/em\u003e. 2015;100:190-209.\u003c/li\u003e\n\u003cli\u003eBenage M, Fraunfelder FW. Vaccine-associated uveitis. \u003cem\u003eMo Med\u003c/em\u003e. 2016;113:48-52\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 3 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"eye","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"eye","sideBox":"Learn more about [Eye](http://www.nature.com/eye/)","snPcode":"41433","submissionUrl":"https://mts-eye.nature.com/cgi-bin/main.plex","title":"Eye","twitterHandle":"@eye_journal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Uvea, Melanoma, COVID-19, Sclera, Scleritis, Oncology","lastPublishedDoi":"10.21203/rs.3.rs-2464691/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2464691/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eTo determine clinical features and outcomes of posterior scleritis masquerading as uveal melanoma following vaccination against COVID-19 and/or COVID-19 infection.\u003c/p\u003e\u003ch2\u003eSubjects/Methods:\u003c/h2\u003e \u003cp\u003eAll patients with posterior scleritis referred to our service to rule out intraocular tumor between February 2021 and June 2022, who previously had COVID-19 vaccination and/or infection (n\u0026thinsp;=\u0026thinsp;8). A retrospective detailed review of patient charts and imaging was carried out.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003ePrevious COVID-19 vaccination was documented in 6 patients (75%) and previous COVID-19 infection and vaccination in 2 patients (25%). Demographic features included mean age of 59 years (median 68, range 5\u0026ndash;86 years), white race (n\u0026thinsp;=\u0026thinsp;7, 87%), and male sex (n\u0026thinsp;=\u0026thinsp;5, 63%). Mean visual acuity at presentation was 0.24 LogMAR (median 0.18, range 0.0-0.70). The main presenting symptom was blurred vision with pain (n\u0026thinsp;=\u0026thinsp;5, 63%). Features that suggested scleritis and not uveal melanoma included pain (n\u0026thinsp;=\u0026thinsp;6, 75%), anterior scleritis (n\u0026thinsp;=\u0026thinsp;3, 38%), disc edema (n\u0026thinsp;=\u0026thinsp;1, 13%), choroidal detachment (n\u0026thinsp;=\u0026thinsp;3, 38%), choroidal folds (n\u0026thinsp;=\u0026thinsp;3, 38%), diffusely thickened scleral wall on ultrasonography (n\u0026thinsp;=\u0026thinsp;2, 25%), Tenon\u0026rsquo;s edema (n\u0026thinsp;=\u0026thinsp;5, 63%), and scleral nodule with medium/high internal reflectivity on ultrasonography (n\u0026thinsp;=\u0026thinsp;4, 50%). Follow-up information at mean of 2 months (range 0.25-7 months) revealed visual acuity at date last seen was mean 0.30 LogMAR (median 0.29, range 0.0-0.54). By 2 months, resolution of \u0026ldquo;tumor\u0026rdquo; was noted in 5/6 (83%) patients with follow-up.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003ePosterior scleritis following COVID-19 vaccination and/or infection can masquerade as choroidal melanoma. At 2 months duration, partial or complete resolution of features with minimal visual consequence was noted.\u003c/p\u003e","manuscriptTitle":"Posterior Scleritis Following COVID-19 Vaccination or Infection Simulating Uveal Melanoma in 8 Consecutive Patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-02-08 20:04:03","doi":"10.21203/rs.3.rs-2464691/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2023-06-13T16:12:29+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"This content is not available.","date":"2023-04-28T14:05:46+00:00","index":2,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2023-04-12T08:23:53+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2023-04-04T16:48:06+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2023-02-06T18:10:55+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-02-01T17:34:31+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-01-12T11:05:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"Eye","date":"2023-01-10T21:37:43+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"eye","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"eye","sideBox":"Learn more about [Eye](http://www.nature.com/eye/)","snPcode":"41433","submissionUrl":"https://mts-eye.nature.com/cgi-bin/main.plex","title":"Eye","twitterHandle":"@eye_journal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"83f269b8-5a88-4249-b2f7-14dfc3d82fdc","owner":[],"postedDate":"February 8th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":18999344,"name":"Biological sciences/Immunology/Infectious diseases/Viral infection"},{"id":18999345,"name":"Biological sciences/Cancer/Eye cancer"},{"id":18999346,"name":"Biological sciences/Immunology/Inflammation"}],"tags":[],"updatedAt":"2023-07-09T07:06:54+00:00","versionOfRecord":{"articleIdentity":"rs-2464691","link":"https://doi.org/10.1038/s41433-023-02656-z","journal":{"identity":"eye","isVorOnly":false,"title":"Eye"},"publishedOn":"2023-07-08 04:00:00","publishedOnDateReadable":"July 8th, 2023"},"versionCreatedAt":"2023-02-08 20:04:03","video":"","vorDoi":"10.1038/s41433-023-02656-z","vorDoiUrl":"https://doi.org/10.1038/s41433-023-02656-z","workflowStages":[]},"version":"v1","identity":"rs-2464691","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2464691","identity":"rs-2464691","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}