Increased incidence and diverse manifestations of Multiple Evanescent White Dot Syndrome during the COVID-19 pandemic

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In this study, we compared the incidence rates of multiple evanescent white dot syndrome (MEWDS) before and during the COVID-19 pandemic at a single center in Korea and analyzed the demographic and clinical features of patients with MEWDS presenting during the COVID-19 pandemic. We categorized patients with MEWDS into two groups according to date of diagnosis. Group 1 included patients diagnosed during the pre-pandemic period (before March 10, 2020), whereas Group 2 included patients diagnosed during the pandemic period (after March 11, 2020). 6 and 12 patients were included in Groups 1 and Group 2, respectively. Among all hospital visits during the pre-pandemic and pandemic periods, 0.011% and 0.030% were due to MEWDS, indicating a significant increase during the pandemic (p = 0.029, B = 2.756). The annual visit rates of patients with MEWDS in 2017–2022 were 0.73, 0.75, 0.78, 1.32, 2.49, and 2.07 per 10,000 population, respectively, corresponding to a significant increase (p = 0.039, B = 1.316). Group 2 included a larger proportion of male patients compared with Group 1 (p < 0.001). Our results imply that the incidence and manifestation of MEWDS are likely to become more diverse in the COVID-19 pandemic era. MEWDS COVID-19 vaccination incidence Figures Figure 1 Figure 2 Figure 3 Introduction Initially described by Jampol et al. 1 in 1984, multiple evanescent white dot syndrome (MEWDS) is characterized by the unilateral presence of multiple gray-white dots at the retinal pigment epithelium or outer retina and foveal granularity. This rare disease predominantly affects young women, with an estimated annual incidence of 0.22 per 100,000 people. 2 Although its precise pathogenesis remains unclear, post-viral autoimmune or auto-inflammatory causes have been hypothesized. 3 In March 2020, the World Health Organization (WHO) declared that the outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had reached pandemic status. 4 As of August 30, 2023, approximately 770 million people worldwide had developed COVID-19, including almost 34 million reported cases in South Korea. 5 To safeguard individuals and contribute to herd immunity, the United States Food and Drug Administration authorized the emergency use of COVID-19 vaccines in December 2020. In South Korea, 86% of the population has received at least the second dose of COVID-19 vaccine. 6 Subsequent global efforts have effectively reduced the morbidity and mortality associated with COVID-19, leading the WHO Director General to declare the end of the COVID-19 public health emergency of international concern on May 5, 2023. Numerous studies have investigated ocular involvement associated with COVID-19 and corresponding vaccines. 7–10 Case reports have described the occurrence of MEWDS after episodes of COVID-19 and vaccination against the disease. 11–14 The COVID-19 pandemic has influenced the incidence and course of certain diseases. 15,16 The present study explored the demographic and clinical characteristics of patients who developed MEWDS during the COVID-19 pandemic. Results Demographics During the study period, 8 and 20 patients were evaluated for inclusion in Groups 1 and 2, respectively; among these patients, 6 and 14 were diagnosed with MEWDS, respectively. In total, 3 patients were misdiagnosed and 5 did not fulfill the diagnostic criteria for MEWDS. Table 1 presents the baseline characteristics of patients of both group. Two of the patients were included in both groups but are only presented in Group 1 in Table 1 . The mean ages were 36.5 ± 13.4 years in Group 1 and 37.58 ± 19.1 years in Group 2 (p = 0.964). The proportions of female patients were 100% in Group 1 and 58% in Group 2, with a statistically significant difference between groups (p < 0.001). The baseline best-corrected visual acuity (BCVA) were 0.2 ± 0.3 in Group 1 and 0.2 ± 0.2 in Group 2 (p = 0.750), and the corresponding final BCVA were 0.0 ± 0.1 and 0.0 ± 0.0 (p = 0.820); these findings did not significantly differ between the groups. There were no significant differences in the time to improvement between Groups 1 and 2 (36.2 ± 14.2 and 33.6 ± 15.5 days, respectively; p = 0.733). There were no complications in Group 1, whereas two patients developed complications in Group 2 (p = 0.529). Incidence rate of MEWDS during pre-pandemic and pandemic period In the pre-pandemic period, 54,262 patients presented to the hospital; MEWDS was diagnosed in 0.011% of those patients. In comparison, 45,944 patients presented to the hospital during the pandemic; MEWDS was diagnosed in 0.030% of those patients, corresponding to a significant increase from the pre-pandemic period (p = 0.029, B = 2.756). The annual visit rates of patients with MEWDS in 2017–2022 were 0.73, 0.75, 0.78, 1.32, 2.49, and 2.07 per 10,000 people, respectively, corresponding to a significant annual increase (p = 0.039, B = 1.316; Fig. 1). MEWDS cases in pandemic period Table 2 presents the characteristics of patients with MEWDS during the pandemic period. Among the 14 patients, 2 developed COVID-19 within 2 weeks, including the youngest patient in the group (Case 5; aged 13 years). Additionally, the oldest patient in the group (aged 78 years) developed MEWDS after COVID-19 vaccination. Two patients developed various features of MEWDS, including Case 2 who developed complicated macular neovascularization (MNV) after 9 months and successfully treated with anti-vascular endothelial growth factor (VEGF) (Fig. 2) and Case 9 who developed MEWDS in both eyes sequentially, rather than simultaneously, along with bacillary layer detachment (BALAD) with subretinal fluid (Fig. 3). As previously mentioned, two patients were included in both groups because of disease recurrence: Case 10 developed right eye MEWDS during the pre-pandemic period, followed by disease recurrence in the same eye 3 years later; Case 14 developed left eye MEWDS during the pre-pandemic period, followed by two disease recurrences in the same eye during the pandemic period. Discussion The COVID-19 pandemic has ushered in a “new normal,” significantly altering daily life and establishing new standards worldwide. The pandemic has also affected the incidence and course of certain diseases. Aydin et al. 15 demonstrated increased frequency and altered clinical features of pediatric uveitis during the pandemic period, compared with the pre-pandemic period. Azar et al. 16 demonstrated a significant increase in the incidence of acute macular neuroretinopathy from 0.66 per 100,000 people in 2019 to 8.97 per 100,000 people in 2020, which may be attributed to the COVID-19 pandemic. The present study was performed upon recognition of the increased number of hospital visits by patients with MEWDS during the pandemic period, compared with the pre-pandemic period. The annual visit rate of patients with MEWDS at our hospital also significantly increased from 2017 to 2022. Finally, the sex distribution differed between the pandemic and pre-pandemic periods. In COVID-19, SARS-CoV-2 targets endothelial cells through the angiotensin-converting enzyme 2 receptor, causing disruption of intercellular junctions, cell swelling, and impaired barrier function. 17,18 When these abnormalities occur in the peripapillary circulation of the retina, inflammation may involve the outer retinal layer. Ocular inflammation after COVID-19 vaccination is caused by molecular mimicry between uveal peptides and vaccine peptide fragments, antigen-specific cell and antibody-mediated hypersensitivity reactions, and adjuvant-induced inflammatory damage. 9,19–21 The pathogenesis of MEWDS, described as “common cold of the retina” by Tavallali and Yannuzzi, 22 involves the entry of viral agents into retinal photoreceptor cells located at the border of the optic nerve and ora serrata, triggering an autoimmune response. 2,23 Therefore, episodes of COVID-19 and vaccination against the disease can increase the risk of MEWDS. Bosello et al. 24 demonstrated that the incidence of MEWDS was significantly higher in autumn, which may be due to the higher incidence of common influenza-like viral illnesses. We believe that increased viral transmission and vaccine use during the pandemic were associated with the increased frequency and altered clinical features of MEWDS. In Group 2, two patients developed MEWDS after COVID-19, including Cases 5 and Case 11. Case 5 was a 13-year-old boy who presented with a 5-day history of blurred vision in the right eye. Because he exhibited cough and chills for 10 days, he was tested by COVID-19 polymerase chain reaction; the result was positive. He had not undergone COVID-19 vaccination because of his young age. Case 11, a 36-year-old man, developed a scotoma 10 days after diagnosis with COVID-19. Despite receiving a second booster vaccination approximately 1 year prior, this was his first episode of COVID-19. Jain et al. 25 reported the case of a 17-year-old boy who developed MEWDS after COVID-19; Zecevic et al. 11 described MEWDS in a patient with concurrent COVID-19. Smeller et al. 12 documented the case of a patient with COVID-19 who developed bilateral MEWDS. Also there was a case after COVID-19 vaccination. Case 7, a 78-year-old man, was the oldest patient in Group 2; he developed blurred vision for 7 days. This patient had received the fourth booster vaccination 2 weeks prior during admission to a nursing hospital. Soifer et al. 13 summarized 13 cases with COVID-19 vaccine-associated MEWDS and found that these patients had clinical features similar to the findings in patients who developed MEWDS after other vaccinations. All three cases of MEWDS associated with COVID-19 and vaccination against the disease occurred in male patients, indicating a significant difference in sex distribution among the groups. Despite the small sample size in the present study, the proportion of female patients was lower (58%) than in previous reports (80–90%). 24,26,27 Cases 5 and 7 had outlier ages, which contributed to the wider age range in Group 2 compared with Group 1; furthermore, Group 2 included the oldest and youngest participants. Two patients with MEWDS developed complications during the pandemic period. Case 2 (Fig. 2), a 40-year-old woman, developed complicated MNV 9 months after diagnosis with MEWDS. OCT demonstrated exudates and OCT angiography revealed MNV. FA showed well-defined hyperfluorescent leakage. This exudative lesion was resolved after anti-VEGF injection and appeared quiescent at the final follow-up. MNV is a rare complication of MEWDS, and few cases have been reported. Parodi et al. 28 performed a prospective study of four patients with MEWDS-related MNV, all of whom were successfully treated with anti-VEGF agents. Chen et al. 29 described four cases of MEWDS accompanied by type 2 MNV. Although the incidence of MNV in patients with MEWDS is unknown, this inflammation driven MNV is rare. Case 9 (Fig. 3), a 23-year-old woman, complained of scotoma and blurred vision in the left eye, along with flu-like symptoms. Fundoscopy revealed juxtapapillary white lesions and OCT exhibited fluid accumulation as bacillary layer detachment (BALAD) with serous retinal datachment in corresponding lesion. Three days later, it was spreaded to the peripheral retina as white dot lesion in the manner characteristic of MEWDS. After 40 days, the left eye lesion had resolved but the patient developed similar symptoms in the right eye. Fundoscopy of the right eye revealed white dot-like lesions. Because the patient exhibited persistent fever and chills, she was evaluated for systemic diseases and diagnosed with Crohn’s disease. Fuganti et al. 30 reported two cases of BALAD associated with acute central serous chorioretinopathy in patients after COVID-19. They described development of BALAD may be related to the systemic inflammatory condition observed in patients with COVID-19. In addition, several cases of Vogt–Koyanagi–Harada disease, in which BALAD is most frequently observed, 31 after COVID-19 and vaccination against the disease have been reported. 32,33 This bilateral, sequentially developed MEWDS accompained with BALAD, was never reported before and we speculated that the underlying Crohn’s disease and the COVID-19 pandemic led to a more severe disease course and variable clinical findings. Two female patients developed disease recurrence and were included in both groups. Case 10 experienced MEWDS before the pandemic, followed by disease recurrence in the right eye during the pandemic. Case 14 experienced the first episode of MEWDS before the pandemic and two disease recurrences during the pandemic. Ramakrishnan et al. 27 reported that 10 of the 73 patients with MEWDS (14%) in their study experienced disease recurrence; this proportion was similar to the present study, in which 2 of the 18 patients in both groups experienced recurrence (11%). Soifer et al. 13 described a case of recurrent MEWDS after COVID-19 vaccination, and they summarized two similar cases that were previously reported. These findings suggest that repeated exposure to viruses and vaccines during the pandemic can predispose an individual to MEWDS recurrence. It is challenging to prove a causal relationship between MEWDS and episodes of COVID-19 or vaccination against the disease. However, previous studies have demonstrated an increased risk of uveitis after COVID-19 vaccination. Testis et al. 9 described 70 patients who exhibited ocular inflammation within 14 days of COVID-19 vaccination, among whom 12.9% had posterior uveitis. Rabinovitch et al. 14 reported 21 cases with uveitis after COVID-19 vaccination: 19 with anterior uveitis and 2 with MEWDS. The investigators suggested that a causal relationship between these conditions was likely based on the short time interval (< 30 days) between vaccination and uveitis; however, according to the WHO classification of adverse drug reactions, all patients had probable or possible causality. In South Korea, more than 87% of individuals have received COVID-19 vaccines and numerous people have experienced COVID-19. Moreover, it is challenging to determine the number of asymptomatic COVID-19 cases. Our results suggest that the complex changes associated with the pandemic, including multiple infections and immunological responses, contributed to the increased incidence of MEWDS and associated variable clinical findings. This study had several limitations. First, the sample size was small due to the low incidence of MEWDS. To overcome this limitation, we acquired data over a long period of time (i.e., 6 years). Second, this was a retrospective study. To minimize variability across data, we applied the recent SUN classification criteria for MEWDS. Third, some cases had missing information related to COVID-19 or vaccination against the disease, making it challenging to determine a causal relationship. Fourth, data were collected from a single center, limiting the generalizability of our results to other populations. Nevertheless, our study is clinically valuable because we demonstrated an increased incidence of MEWDS during the pandemic period, compared with the pre-pandemic period. Future multicenter studies with a larger sample size are needed to clearly characterize the relationship between COVID-19 and MEWDS. In conclusion, we observed a significantly greater number of patients with MEWDS presenting to our hospital during the COVID-19 pandemic period, compared with the pre-pandemic period. Furthermore, the annual visit rate of patients with MEWDS significantly increased over the 6-year study period. Considering the increased exposure to viruses and vaccines during the COVID-19 pandemic, the demographic and clinical features of MEWDS are likely to become more diverse. Methods This study was conducted in accordance with the Declaration of Helsinki. The study protocol was approved by the Institutional Review Board of Konyang University Hospital, Republic of Korea (No. 2023-09-015). The need for informed consent was waived by Konyang University due to the retrospective study design. Study population In this observational, single-center, retrospective study, we comprehensively reviewed the electronic medical records of patients diagnosed with MEWDS between March 11, 2017, and March 10, 2023. The records were independently reviewed by two retina specialists (LSC and SYY) to identify patients who fulfilled the classification criteria for MEWDS published by the Standardization of Uveitis Nomenclature (SUN) working group in 2021. 26 These criteria include multifocal chorioretinal gray-white spots with foveal granularity; characteristic findings on fluorescein angiography (FA) or optical coherence tomography (OCT) extending from the retinal pigment epithelium into and/or through the ellipsoid zone into the outer nuclear layer of the retina; and absent to mild anterior chamber and vitreous inflammation. Patients were categorized into two groups according to date of diagnosis. Group 1 included patients diagnosed in the pre-pandemic period (between March 11, 2017, and March 10, 2020), whereas Group 2 included patients diagnosed during the pandemic (between March 11, 2020, and March 10, 2023). Demographic variables were compared between the groups, and specific cases from Group 2 were analyzed in detail. Data analyses Statistical analysis was performed using PASW Statistics software (version 20; IBM Corp., Armonk, NY, USA). Data are expressed as means ± standard deviations. Categorical variables were compared between groups using Fisher’s exact test, whereas continuous variables were compared using the Mann-Whitney U test. Poisson regression was used to compare the proportion of patients diagnosed with MEWDS between the pre-pandemic and pandemic periods and their annual visit rate. P-values < 0.05 were considered indicative of statistical significance. Declarations Author Contribution Conceptualization: Y.Y.S, S.C.LData curation: Y.Y.S, M.W.L.Formal analysis: Y.Y.S., M.W.L.Investigation: Y.Y.S. J.T.K, Y.S.C.Supervision: S.C.L, M.W.LWriting – original draft: Y.Y.S., Writing – review & editing: Y.Y.S., J.T.K., Y.S.C., M.W.L, S.C.L There are no financial conflicts of interest to disclose and there are no funders to report for this article. References Jampol, L. M., Sieving, P. A., Pugh, D., Fishman, G. A. & Gilbert, H. Multiple Evanescent White Dot Syndrome: I. Clinical Findings. Archives of Ophthalmology 102 , 671-674, doi:10.1001/archopht.1984.01040030527008 (1984). Abu-Yaghi, N. E., Hartono, S. P., Hodge, D. O., Pulido, J. S. & Bakri, S. J. White Dot Syndromes: A 20-year Study of Incidence, Clinical Features, and Outcomes. Ocular Immunology and Inflammation 19 , 426-430, doi:10.3109/09273948.2011.624287 (2011). Lages, V., Mantovani, A., Papadia, M. & Herbort, C. P. MEWDS is a true primary choriocapillaritis and basic mechanisms do not seem to differ from other choriocapillaritis entities. J Curr Ophthalmol 30 , 281-286, doi:10.1016/j.joco.2018.09.009 (2018). 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Case series bacillary layer detachment associated with acute central serous chorioretinopathy in patients with COVID-19. Am J Ophthalmol Case Rep 28 , 101690, doi:10.1016/j.ajoc.2022.101690 (2022). Ramtohul, P. et al. BACILLARY LAYER DETACHMENT: MULTIMODAL IMAGING AND HISTOLOGIC EVIDENCE OF A NOVEL OPTICAL COHERENCE TOMOGRAPHY TERMINOLOGY: Literature Review and Proposed Theory. Retina 41 , 2193-2207, doi:10.1097/iae.0000000000003217 (2021). Manni, P., Saturno, M. C. & Accorinti, M. Vogt-Koyanagi-Harada Disease and COVID. J Clin Med 12 , doi:10.3390/jcm12196242 (2023). de Queiroz Tavares Ferreira, F. et al. Possible Association between Vogt-Koyanagi-Harada Disease and Coronavirus Disease Vaccine: A Report of Four Cases. Ocul Immunol Inflamm 31 , 1134-1140, doi:10.1080/09273948.2022.2093756 (2023). Tables Table 1. Baseline characteristics of both group. Group 1 (n = 6) Group 2 (n = 12) P-value Age 36.50 ± 13.43 (20 - 58) 37.58 ± 19.06 (13 - 78) 0.964 † Sex (M : F) 0 : 6 5 : 7 < 0.001 * Laterality (R : L) 4 : 2 5 : 6 0.620* SE -4.98 ± 4.0 -3.53 ± 4.27 0.456 † Baseline BCVA (LogMAR) 0.18 ± 0.30 0.18 ± 0.24 0.750 † Time for resolution (Days) 36.17 ± 14.22 33.64 ± 15.49 0.733 † Final BCVA (LogMAR) 0.03 ± 0.05 0.02 ± 0.04 0.820 † Complication 0 2 (16.7%) 0.529* †Mann-Whitney, *Fisher-exact test; SE = Spherical equivalent. BCVA = Best corrected visual acuity. P-values that are statistically significant are in bold font. Table 2. The summary of MEWDS cases in pandemic period. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 07 May, 2024 Reviews received at journal 05 May, 2024 Reviews received at journal 25 Apr, 2024 Reviewers agreed at journal 16 Apr, 2024 Reviewers agreed at journal 14 Apr, 2024 Reviewers invited by journal 14 Apr, 2024 Editor assigned by journal 04 Mar, 2024 Editor invited by journal 01 Mar, 2024 Submission checks completed at journal 01 Mar, 2024 First submitted to journal 13 Feb, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-3953271","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":276369819,"identity":"285dc268-c8a8-4e42-857e-fb0488fa4bd8","order_by":0,"name":"Yong Yeon Song","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+0lEQVRIiWNgGAWjYBACPjDJBiKYj0HY7AS0sCFItjQImxlEJhClhccMIkRQC3v7xccFZQz2Bjdyvj34uWObPB8zA9uDjz/waOE5U2w84xxD4oYbudsNe8/cNmxjZmA3nIHPFomcNGnetv8JBjdyt0nwtt1mBGphk+bBp0X+Tfpv3jaww55J/m27bQ/W8gevLezHmIFaGDfcyGEDWnc7EawFr/d5cpileYB+mXnmmZm0bNvt5DZmxjbJnjTcWvjZjz/8zAMMMb7jyc8k37bdtp3f3nxM4ocNbi3A6DAAUwoX4G5hbMCnHgjYH4Ap+f4DBBSOglEwCkbBiAUA1w9KMGY94QgAAAAASUVORK5CYII=","orcid":"","institution":"Onnuri Eye Hospital","correspondingAuthor":true,"prefix":"","firstName":"Yong","middleName":"Yeon","lastName":"Song","suffix":""},{"id":276369820,"identity":"219de04c-d531-4995-a304-36b0faf73d4a","order_by":1,"name":"Jung Tae Kim","email":"","orcid":"","institution":"Konyang University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Jung","middleName":"Tae","lastName":"Kim","suffix":""},{"id":276369821,"identity":"cc333b49-f6eb-43f4-aafb-8b1685523bd9","order_by":2,"name":"Young Suk Chang","email":"","orcid":"","institution":"Konyang University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Young","middleName":"Suk","lastName":"Chang","suffix":""},{"id":276369822,"identity":"c063f9ff-efc5-426a-8aff-650db911d174","order_by":3,"name":"Min-Woo Lee","email":"","orcid":"","institution":"Konyang University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Min-Woo","middleName":"","lastName":"Lee","suffix":""},{"id":276369823,"identity":"3ec03061-827f-42af-ba5c-8ff0e09bab55","order_by":4,"name":"Sung Chul Lee","email":"","orcid":"","institution":"Konyang University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Sung","middleName":"Chul","lastName":"Lee","suffix":""}],"badges":[],"createdAt":"2024-02-13 10:16:00","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3953271/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3953271/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":52033800,"identity":"47a3f4a6-73ba-4ba5-883b-6df116dfb4f0","added_by":"auto","created_at":"2024-03-05 16:42:52","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":47832,"visible":true,"origin":"","legend":"\u003cp\u003eAnnual visit rate (per 10,000 people) of patients with multiple evanescent white dot syndrome (MEWDS) in our hospital. Each year represents the period from March 11 of the indicated year to March 10 of the next year. Dotted line indicates the declaration of the COVID-19 global pandemic. The annual visit rates of MEWDS in 2017–2022 were 0.73, 0.75, 0.78, 1.32, 2.49, and 2.07 per 10,000 people, corresponding to a significant increase over the study period.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-3953271/v1/adc01b464c4f60f585dd751a.png"},{"id":52033802,"identity":"333522f7-4c6b-42da-a21d-5df8e8ddd2c9","added_by":"auto","created_at":"2024-03-05 16:42:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1225021,"visible":true,"origin":"","legend":"\u003cp\u003eCase 2, a 40-year-old woman, developed macular neovascularization (MNV) 9 months after diagnosis with multiple evanescent white dot syndrome (MEWDS). (A) Fundus photography (FP) revealed multiple gray-white lesions at the posterior pole. (B) Fluorescein angiography (FA) demonstrated a “wreath-like” pattern of chorioretinal lesions, whereas indocyanine green angiography (IA) showed hypofluorescence of the dots during the late phase. (C) After 9 months, FP revealed resolution of the white dot-like lesions and development of a yellowish foveal lesion. (D) FA demonstrated a distinct hyperfluorescent spot and IA revealed hypofluorescence. (E) Optical coherence tomography (OCT) showed a subretinal hyperreflective material and a small amount of subretinal fluid. (F) OCT angiography demonstrated prominent MNV.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-3953271/v1/b5306757a60d99dd4e19ae83.png"},{"id":52033801,"identity":"d4c0ed6f-cf79-4330-8a2e-e4a3fa030d7a","added_by":"auto","created_at":"2024-03-05 16:42:53","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1118998,"visible":true,"origin":"","legend":"\u003cp\u003eCase 9, a 23-year-old woman, developed bacillary layer detachement (BALAD). (A) At the first visit, fundus photography showed a whitish lesion in the juxtapapillary region. (B) Optical coherence tomography (OCT) demonstrated BALAD with subretinal fluid. (C) After 3 days, the lesion extended beyond the peripheral retina as white dot-like lesions, similar to multiple evanescent white dot syndrome (MEWDS). (D) OCT revealed disruption of the ellipsoid zone. (E, F) After 40 days, the lesion in the left eye disappeared; however, the patient experienced similar symptoms in the right eye, with white dot-like lesions on fundoscopy\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-3953271/v1/c229fd773fac05fa13e5ee9f.png"},{"id":52034645,"identity":"aef1d1e6-6e7f-40b7-a79c-4d7cddb5a6a0","added_by":"auto","created_at":"2024-03-05 16:50:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3276855,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3953271/v1/2bf11b9b-7613-4a14-a2ac-de249783bf6f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Increased incidence and diverse manifestations of Multiple Evanescent White Dot Syndrome during the COVID-19 pandemic","fulltext":[{"header":"Introduction","content":"\u003cp\u003eInitially described by Jampol et al. \u003csup\u003e1\u003c/sup\u003e in 1984, multiple evanescent white dot syndrome (MEWDS) is characterized by the unilateral presence of multiple gray-white dots at the retinal pigment epithelium or outer retina and foveal granularity. This rare disease predominantly affects young women, with an estimated annual incidence of 0.22 per 100,000 people. \u003csup\u003e2\u003c/sup\u003e Although its precise pathogenesis remains unclear, post-viral autoimmune or auto-inflammatory causes have been hypothesized. \u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn March 2020, the World Health Organization (WHO) declared that the outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had reached pandemic status. \u003csup\u003e4\u003c/sup\u003e As of August 30, 2023, approximately 770\u0026nbsp;million people worldwide had developed COVID-19, including almost 34\u0026nbsp;million reported cases in South Korea. \u003csup\u003e5\u003c/sup\u003e To safeguard individuals and contribute to herd immunity, the United States Food and Drug Administration authorized the emergency use of COVID-19 vaccines in December 2020. In South Korea, 86% of the population has received at least the second dose of COVID-19 vaccine. \u003csup\u003e6\u003c/sup\u003e Subsequent global efforts have effectively reduced the morbidity and mortality associated with COVID-19, leading the WHO Director General to declare the end of the COVID-19 public health emergency of international concern on May 5, 2023.\u003c/p\u003e \u003cp\u003eNumerous studies have investigated ocular involvement associated with COVID-19 and corresponding vaccines. \u003csup\u003e7\u0026ndash;10\u003c/sup\u003e Case reports have described the occurrence of MEWDS after episodes of COVID-19 and vaccination against the disease. \u003csup\u003e11\u0026ndash;14\u003c/sup\u003e The COVID-19 pandemic has influenced the incidence and course of certain diseases. \u003csup\u003e15,16\u003c/sup\u003e The present study explored the demographic and clinical characteristics of patients who developed MEWDS during the COVID-19 pandemic.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eDemographics\u003c/h2\u003e \u003cp\u003eDuring the study period, 8 and 20 patients were evaluated for inclusion in Groups 1 and 2, respectively; among these patients, 6 and 14 were diagnosed with MEWDS, respectively. In total, 3 patients were misdiagnosed and 5 did not fulfill the diagnostic criteria for MEWDS. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e presents the baseline characteristics of patients of both group. Two of the patients were included in both groups but are only presented in Group 1 in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The mean ages were 36.5\u0026thinsp;\u0026plusmn;\u0026thinsp;13.4 years in Group 1 and 37.58\u0026thinsp;\u0026plusmn;\u0026thinsp;19.1 years in Group 2 (p\u0026thinsp;=\u0026thinsp;0.964). The proportions of female patients were 100% in Group 1 and 58% in Group 2, with a statistically significant difference between groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The baseline best-corrected visual acuity (BCVA) were 0.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3 in Group 1 and 0.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2 in Group 2 (p\u0026thinsp;=\u0026thinsp;0.750), and the corresponding final BCVA were 0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1 and 0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0 (p\u0026thinsp;=\u0026thinsp;0.820); these findings did not significantly differ between the groups. There were no significant differences in the time to improvement between Groups 1 and 2 (36.2\u0026thinsp;\u0026plusmn;\u0026thinsp;14.2 and 33.6\u0026thinsp;\u0026plusmn;\u0026thinsp;15.5 days, respectively; p\u0026thinsp;=\u0026thinsp;0.733). There were no complications in Group 1, whereas two patients developed complications in Group 2 (p\u0026thinsp;=\u0026thinsp;0.529).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eIncidence rate of MEWDS during pre-pandemic and pandemic period\u003c/h2\u003e \u003cp\u003eIn the pre-pandemic period, 54,262 patients presented to the hospital; MEWDS was diagnosed in 0.011% of those patients. In comparison, 45,944 patients presented to the hospital during the pandemic; MEWDS was diagnosed in 0.030% of those patients, corresponding to a significant increase from the pre-pandemic period (p\u0026thinsp;=\u0026thinsp;0.029, B\u0026thinsp;=\u0026thinsp;2.756). The annual visit rates of patients with MEWDS in 2017\u0026ndash;2022 were 0.73, 0.75, 0.78, 1.32, 2.49, and 2.07 per 10,000 people, respectively, corresponding to a significant annual increase (p\u0026thinsp;=\u0026thinsp;0.039, B\u0026thinsp;=\u0026thinsp;1.316; Fig.\u0026nbsp;1).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eMEWDS cases in pandemic period\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e presents the characteristics of patients with MEWDS during the pandemic period. Among the 14 patients, 2 developed COVID-19 within 2 weeks, including the youngest patient in the group (Case 5; aged 13 years). Additionally, the oldest patient in the group (aged 78 years) developed MEWDS after COVID-19 vaccination. Two patients developed various features of MEWDS, including Case 2 who developed complicated macular neovascularization (MNV) after 9 months and successfully treated with anti-vascular endothelial growth factor (VEGF) (Fig.\u0026nbsp;2) and Case \u003cspan refid=\"FPar1\" class=\"InternalRef\"\u003e9\u003c/span\u003e who developed MEWDS in both eyes sequentially, rather than simultaneously, along with bacillary layer detachment (BALAD) with subretinal fluid (Fig.\u0026nbsp;3). As previously mentioned, two patients were included in both groups because of disease recurrence: Case 10 developed right eye MEWDS during the pre-pandemic period, followed by disease recurrence in the same eye 3 years later; Case 14 developed left eye MEWDS during the pre-pandemic period, followed by two disease recurrences in the same eye during the pandemic period.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe COVID-19 pandemic has ushered in a \u0026ldquo;new normal,\u0026rdquo; significantly altering daily life and establishing new standards worldwide. The pandemic has also affected the incidence and course of certain diseases. Aydin et al. \u003csup\u003e15\u003c/sup\u003e demonstrated increased frequency and altered clinical features of pediatric uveitis during the pandemic period, compared with the pre-pandemic period. Azar et al. \u003csup\u003e16\u003c/sup\u003e demonstrated a significant increase in the incidence of acute macular neuroretinopathy from 0.66 per 100,000 people in 2019 to 8.97 per 100,000 people in 2020, which may be attributed to the COVID-19 pandemic. The present study was performed upon recognition of the increased number of hospital visits by patients with MEWDS during the pandemic period, compared with the pre-pandemic period. The annual visit rate of patients with MEWDS at our hospital also significantly increased from 2017 to 2022. Finally, the sex distribution differed between the pandemic and pre-pandemic periods.\u003c/p\u003e \u003cp\u003eIn COVID-19, SARS-CoV-2 targets endothelial cells through the angiotensin-converting enzyme 2 receptor, causing disruption of intercellular junctions, cell swelling, and impaired barrier function. \u003csup\u003e17,18\u003c/sup\u003e When these abnormalities occur in the peripapillary circulation of the retina, inflammation may involve the outer retinal layer. Ocular inflammation after COVID-19 vaccination is caused by molecular mimicry between uveal peptides and vaccine peptide fragments, antigen-specific cell and antibody-mediated hypersensitivity reactions, and adjuvant-induced inflammatory damage. \u003csup\u003e9,19\u0026ndash;21\u003c/sup\u003e The pathogenesis of MEWDS, described as \u0026ldquo;common cold of the retina\u0026rdquo; by Tavallali and Yannuzzi, \u003csup\u003e22\u003c/sup\u003e involves the entry of viral agents into retinal photoreceptor cells located at the border of the optic nerve and ora serrata, triggering an autoimmune response. \u003csup\u003e2,23\u003c/sup\u003e Therefore, episodes of COVID-19 and vaccination against the disease can increase the risk of MEWDS. Bosello et al. \u003csup\u003e24\u003c/sup\u003e demonstrated that the incidence of MEWDS was significantly higher in autumn, which may be due to the higher incidence of common influenza-like viral illnesses. We believe that increased viral transmission and vaccine use during the pandemic were associated with the increased frequency and altered clinical features of MEWDS.\u003c/p\u003e \u003cp\u003eIn Group 2, two patients developed MEWDS after COVID-19, including Cases 5 and Case 11. Case 5 was a 13-year-old boy who presented with a 5-day history of blurred vision in the right eye. Because he exhibited cough and chills for 10 days, he was tested by COVID-19 polymerase chain reaction; the result was positive. He had not undergone COVID-19 vaccination because of his young age. Case 11, a 36-year-old man, developed a scotoma 10 days after diagnosis with COVID-19. Despite receiving a second booster vaccination approximately 1 year prior, this was his first episode of COVID-19. Jain et al. \u003csup\u003e25\u003c/sup\u003e reported the case of a 17-year-old boy who developed MEWDS after COVID-19; Zecevic et al. \u003csup\u003e11\u003c/sup\u003e described MEWDS in a patient with concurrent COVID-19. Smeller et al. \u003csup\u003e12\u003c/sup\u003e documented the case of a patient with COVID-19 who developed bilateral MEWDS. Also there was a case after COVID-19 vaccination. Case 7, a 78-year-old man, was the oldest patient in Group 2; he developed blurred vision for 7 days. This patient had received the fourth booster vaccination 2 weeks prior during admission to a nursing hospital. Soifer et al. \u003csup\u003e13\u003c/sup\u003e summarized 13 cases with COVID-19 vaccine-associated MEWDS and found that these patients had clinical features similar to the findings in patients who developed MEWDS after other vaccinations. All three cases of MEWDS associated with COVID-19 and vaccination against the disease occurred in male patients, indicating a significant difference in sex distribution among the groups. Despite the small sample size in the present study, the proportion of female patients was lower (58%) than in previous reports (80\u0026ndash;90%).\u003csup\u003e24,26,27\u003c/sup\u003e Cases 5 and 7 had outlier ages, which contributed to the wider age range in Group 2 compared with Group 1; furthermore, Group 2 included the oldest and youngest participants.\u003c/p\u003e \u003cp\u003eTwo patients with MEWDS developed complications during the pandemic period. Case 2 (Fig.\u0026nbsp;2), a 40-year-old woman, developed complicated MNV 9 months after diagnosis with MEWDS. OCT demonstrated exudates and OCT angiography revealed MNV. FA showed well-defined hyperfluorescent leakage. This exudative lesion was resolved after anti-VEGF injection and appeared quiescent at the final follow-up. MNV is a rare complication of MEWDS, and few cases have been reported. Parodi et al. \u003csup\u003e28\u003c/sup\u003e performed a prospective study of four patients with MEWDS-related MNV, all of whom were successfully treated with anti-VEGF agents. Chen et al. \u003csup\u003e29\u003c/sup\u003e described four cases of MEWDS accompanied by type 2 MNV. Although the incidence of MNV in patients with MEWDS is unknown, this inflammation driven MNV is rare.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCase 9\u003c/strong\u003e \u003cp\u003e(Fig.\u0026nbsp;3), a 23-year-old woman, complained of scotoma and blurred vision in the left eye, along with flu-like symptoms. Fundoscopy revealed juxtapapillary white lesions and OCT exhibited fluid accumulation as bacillary layer detachment (BALAD) with serous retinal datachment in corresponding lesion. Three days later, it was spreaded to the peripheral retina as white dot lesion in the manner characteristic of MEWDS. After 40 days, the left eye lesion had resolved but the patient developed similar symptoms in the right eye. Fundoscopy of the right eye revealed white dot-like lesions. Because the patient exhibited persistent fever and chills, she was evaluated for systemic diseases and diagnosed with Crohn\u0026rsquo;s disease. Fuganti et al. \u003csup\u003e30\u003c/sup\u003e reported two cases of BALAD associated with acute central serous chorioretinopathy in patients after COVID-19. They described development of BALAD may be related to the systemic inflammatory condition observed in patients with COVID-19. In addition, several cases of Vogt\u0026ndash;Koyanagi\u0026ndash;Harada disease, in which BALAD is most frequently observed, \u003csup\u003e31\u003c/sup\u003e after COVID-19 and vaccination against the disease have been reported. \u003csup\u003e32,33\u003c/sup\u003e This bilateral, sequentially developed MEWDS accompained with BALAD, was never reported before and we speculated that the underlying Crohn\u0026rsquo;s disease and the COVID-19 pandemic led to a more severe disease course and variable clinical findings.\u003c/p\u003e \u003c/p\u003e \u003cp\u003eTwo female patients developed disease recurrence and were included in both groups. Case 10 experienced MEWDS before the pandemic, followed by disease recurrence in the right eye during the pandemic. Case 14 experienced the first episode of MEWDS before the pandemic and two disease recurrences during the pandemic. Ramakrishnan et al. \u003csup\u003e27\u003c/sup\u003e reported that 10 of the 73 patients with MEWDS (14%) in their study experienced disease recurrence; this proportion was similar to the present study, in which 2 of the 18 patients in both groups experienced recurrence (11%). Soifer et al. \u003csup\u003e13\u003c/sup\u003e described a case of recurrent MEWDS after COVID-19 vaccination, and they summarized two similar cases that were previously reported. These findings suggest that repeated exposure to viruses and vaccines during the pandemic can predispose an individual to MEWDS recurrence.\u003c/p\u003e \u003cp\u003eIt is challenging to prove a causal relationship between MEWDS and episodes of COVID-19 or vaccination against the disease. However, previous studies have demonstrated an increased risk of uveitis after COVID-19 vaccination. Testis et al. \u003csup\u003e9\u003c/sup\u003e described 70 patients who exhibited ocular inflammation within 14 days of COVID-19 vaccination, among whom 12.9% had posterior uveitis. Rabinovitch et al. \u003csup\u003e14\u003c/sup\u003e reported 21 cases with uveitis after COVID-19 vaccination: 19 with anterior uveitis and 2 with MEWDS. The investigators suggested that a causal relationship between these conditions was likely based on the short time interval (\u0026lt;\u0026thinsp;30 days) between vaccination and uveitis; however, according to the WHO classification of adverse drug reactions, all patients had probable or possible causality. In South Korea, more than 87% of individuals have received COVID-19 vaccines and numerous people have experienced COVID-19. Moreover, it is challenging to determine the number of asymptomatic COVID-19 cases. Our results suggest that the complex changes associated with the pandemic, including multiple infections and immunological responses, contributed to the increased incidence of MEWDS and associated variable clinical findings.\u003c/p\u003e \u003cp\u003eThis study had several limitations. First, the sample size was small due to the low incidence of MEWDS. To overcome this limitation, we acquired data over a long period of time (i.e., 6 years). Second, this was a retrospective study. To minimize variability across data, we applied the recent SUN classification criteria for MEWDS. Third, some cases had missing information related to COVID-19 or vaccination against the disease, making it challenging to determine a causal relationship. Fourth, data were collected from a single center, limiting the generalizability of our results to other populations. Nevertheless, our study is clinically valuable because we demonstrated an increased incidence of MEWDS during the pandemic period, compared with the pre-pandemic period. Future multicenter studies with a larger sample size are needed to clearly characterize the relationship between COVID-19 and MEWDS.\u003c/p\u003e \u003cp\u003eIn conclusion, we observed a significantly greater number of patients with MEWDS presenting to our hospital during the COVID-19 pandemic period, compared with the pre-pandemic period. Furthermore, the annual visit rate of patients with MEWDS significantly increased over the 6-year study period. Considering the increased exposure to viruses and vaccines during the COVID-19 pandemic, the demographic and clinical features of MEWDS are likely to become more diverse.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis study was conducted in accordance with the Declaration of Helsinki. The study protocol was approved by the Institutional Review Board of Konyang University Hospital, Republic of Korea (No. 2023-09-015). The need for informed consent was waived by Konyang University due to the retrospective study design.\u003c/p\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eStudy population\u003c/h2\u003e\n \u003cp\u003eIn this observational, single-center, retrospective study, we comprehensively reviewed the electronic medical records of patients diagnosed with MEWDS between March 11, 2017, and March 10, 2023. The records were independently reviewed by two retina specialists (LSC and SYY) to identify patients who fulfilled the classification criteria for MEWDS published by the Standardization of Uveitis Nomenclature (SUN) working group in 2021. \u003csup\u003e26\u003c/sup\u003e These criteria include multifocal chorioretinal gray-white spots with foveal granularity; characteristic findings on fluorescein angiography (FA) or optical coherence tomography (OCT) extending from the retinal pigment epithelium into and/or through the ellipsoid zone into the outer nuclear layer of the retina; and absent to mild anterior chamber and vitreous inflammation. Patients were categorized into two groups according to date of diagnosis. Group 1 included patients diagnosed in the pre-pandemic period (between March 11, 2017, and March 10, 2020), whereas Group 2 included patients diagnosed during the pandemic (between March 11, 2020, and March 10, 2023). Demographic variables were compared between the groups, and specific cases from Group 2 were analyzed in detail.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n \u003ch2\u003eData analyses\u003c/h2\u003e\n \u003cp\u003eStatistical analysis was performed using PASW Statistics software (version 20; IBM Corp., Armonk, NY, USA). Data are expressed as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviations. Categorical variables were compared between groups using Fisher\u0026rsquo;s exact test, whereas continuous variables were compared using the Mann-Whitney U test. Poisson regression was used to compare the proportion of patients diagnosed with MEWDS between the pre-pandemic and pandemic periods and their annual visit rate. P-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered indicative of statistical significance.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConceptualization: Y.Y.S, S.C.LData curation: Y.Y.S, M.W.L.Formal analysis: Y.Y.S., M.W.L.Investigation: Y.Y.S. J.T.K, Y.S.C.Supervision: S.C.L, M.W.LWriting \u0026ndash; original draft: Y.Y.S., Writing \u0026ndash; review \u0026amp; editing: Y.Y.S., J.T.K., Y.S.C., M.W.L, S.C.L\u003c/p\u003e\u003cp\u003eThere are no financial conflicts of interest to disclose and there are no funders to report for this article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJampol, L. M., Sieving, P. A., Pugh, D., Fishman, G. A. \u0026amp; Gilbert, H. Multiple Evanescent White Dot Syndrome: I. 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Vogt-Koyanagi-Harada Disease and COVID. \u003cem\u003eJ Clin Med\u003c/em\u003e \u003cstrong\u003e12\u003c/strong\u003e, doi:10.3390/jcm12196242 (2023).\u003c/li\u003e\n\u003cli\u003ede Queiroz Tavares Ferreira, F.\u003cem\u003e et al.\u003c/em\u003e Possible Association between Vogt-Koyanagi-Harada Disease and Coronavirus Disease Vaccine: A Report of Four Cases. \u003cem\u003eOcul Immunol Inflamm\u003c/em\u003e \u003cstrong\u003e31\u003c/strong\u003e, 1134-1140, doi:10.1080/09273948.2022.2093756 (2023).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Baseline characteristics of both group.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.333333333333332%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003eGroup 1 (n = 6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003eGroup 2 (n = 12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.333333333333332%\" valign=\"top\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e36.50\u0026nbsp;\u0026plusmn;\u0026nbsp;13.43\u003cbr\u003e\u0026nbsp;(20 - 58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e37.58\u0026nbsp;\u0026plusmn; 19.06\u003cbr\u003e\u0026nbsp;(13 - 78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.964\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.333333333333332%\" valign=\"top\"\u003e\n \u003cp\u003eSex (M : F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e0 : 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e5 : 7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 0.001\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.333333333333332%\" valign=\"top\"\u003e\n \u003cp\u003eLaterality (R : L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e4 : 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e5 : 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.620*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.333333333333332%\" valign=\"top\"\u003e\n \u003cp\u003eSE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e-4.98\u0026nbsp;\u0026plusmn; 4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e-3.53\u0026nbsp;\u0026plusmn; 4.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.456\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.333333333333332%\" valign=\"top\"\u003e\n \u003cp\u003eBaseline BCVA\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(LogMAR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e0.18\u0026nbsp;\u0026plusmn; 0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.18\u0026nbsp;\u0026plusmn; 0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.750\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.333333333333332%\" valign=\"top\"\u003e\n \u003cp\u003eTime for resolution\u003c/p\u003e\n \u003cp\u003e(Days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e36.17\u0026nbsp;\u0026plusmn; 14.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e33.64\u0026nbsp;\u0026plusmn; 15.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.733\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.333333333333332%\" valign=\"top\"\u003e\n \u003cp\u003eFinal BCVA\u003cbr\u003e\u0026nbsp;(LogMAR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e0.03\u0026nbsp;\u0026plusmn; 0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.02\u0026nbsp;\u0026plusmn; 0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.820\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.333333333333332%\" valign=\"top\"\u003e\n \u003cp\u003eComplication\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e2 (16.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.529*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026dagger;Mann-Whitney, *Fisher-exact test; SE = Spherical equivalent. BCVA = Best corrected visual acuity.\u003c/p\u003e\n\u003cp\u003eP-values that are statistically significant are in bold font.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eTable 2. The summary of MEWDS cases in pandemic period.\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/122228_c8a1650c59388082/122228_custom_files/img1709628825.png\"\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\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":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"MEWDS, COVID-19, vaccination, incidence","lastPublishedDoi":"10.21203/rs.3.rs-3953271/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3953271/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe advent of coronavirus disease 2019 (COVID-19) pandemic has affected the incidence and course of various diseases and numerous studies have investigated ocular involvement associated with COVID-19 and corresponding vaccines. In this study, we compared the incidence rates of multiple evanescent white dot syndrome (MEWDS) before and during the COVID-19 pandemic at a single center in Korea and analyzed the demographic and clinical features of patients with MEWDS presenting during the COVID-19 pandemic. We categorized patients with MEWDS into two groups according to date of diagnosis. Group 1 included patients diagnosed during the pre-pandemic period (before March 10, 2020), whereas Group 2 included patients diagnosed during the pandemic period (after March 11, 2020). 6 and 12 patients were included in Groups 1 and Group 2, respectively. Among all hospital visits during the pre-pandemic and pandemic periods, 0.011% and 0.030% were due to MEWDS, indicating a significant increase during the pandemic (p\u0026thinsp;=\u0026thinsp;0.029, B\u0026thinsp;=\u0026thinsp;2.756). The annual visit rates of patients with MEWDS in 2017\u0026ndash;2022 were 0.73, 0.75, 0.78, 1.32, 2.49, and 2.07 per 10,000 population, respectively, corresponding to a significant increase (p\u0026thinsp;=\u0026thinsp;0.039, B\u0026thinsp;=\u0026thinsp;1.316). Group 2 included a larger proportion of male patients compared with Group 1 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Our results imply that the incidence and manifestation of MEWDS are likely to become more diverse in the COVID-19 pandemic era.\u003c/p\u003e","manuscriptTitle":"Increased incidence and diverse manifestations of Multiple Evanescent White Dot Syndrome during the COVID-19 pandemic","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-05 16:42:48","doi":"10.21203/rs.3.rs-3953271/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-05-07T04:27:50+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-05T21:22:40+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-04-25T08:21:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"8b1b47c9-871f-416f-826c-42a3890c04c2_SNPRID","date":"2024-04-16T15:43:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"3a4b0f04-8230-4e96-9485-91ff55ea8a50","date":"2024-04-14T15:45:40+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-04-14T15:11:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-03-04T23:12:32+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-03-01T16:35:24+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-03-01T15:48:34+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-02-13T10:12:54+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"01e4ea28-0dd4-4b9d-869f-9262499a51aa","owner":[],"postedDate":"March 5th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-05-27T08:30:53+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-05 16:42:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3953271","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3953271","identity":"rs-3953271","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}