AbstractThe 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 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.

摘要2019年冠状病毒病（COVID-19）大流行的出现影响了各种疾病的发病率和病程，许多研究已经调查了与COVID-19和相应疫苗相关的眼部受累。在这项研究中，我们在韩国的一个中心比较了COVID-19大流行之前和期间多发性消失白点综合征（MEWDS）的发病率，并分析了COVID-19大流行期间出现的MEWDS患者的人口统计学和临床特征。

We categorized patients with MEWDS into two groups according to date of diagnosis. Pre-COVID19 group included patients diagnosed during the pre-pandemic period (between March 11, 2017, and March 10, 2020), whereas post-COVID19 group included patients diagnosed during the pandemic period (between March 11, 2020, and March 10, 2023).

我们根据诊断日期将MEWDS患者分为两组。前COVID19组包括在大流行前期（2017年3月11日至2020年3月10日）诊断的患者，而后COVID19组包括在大流行期间（2020年3月11日至2023年3月10日）诊断的患者。

6 and 12 patients were included in pre-COVID19 group and post-COVID19 group, 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 incidence 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).

COVID19前组和COVID19后组分别纳入6例和12例患者。在大流行前和大流行期间的所有医院就诊中，0.011%和0.030%是由于MEWD引起的，表明大流行期间显着增加（p = 0.029，B = 2.756）。2017-2022年MEWD患者的年发病率分别为每10000人0.73、0.75、0.78、1.32、2.49和2.07，相应地显着增加（p = 0.039，B = 1.316）。

Our results imply that the incidence and manifestation of MEWDS are likely to become more diverse in the COVID-19 pandemic era..

我们的研究结果表明，在新冠肺炎大流行时代，MEWD的发病率和表现可能会变得更加多样化。。

IntroductionInitially 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 people2.

引言最初由Jampol等人于1984年描述，多发性消失白点综合征（MEWDS）的特征是在视网膜色素上皮或视网膜外层和中央凹颗粒处单侧存在多个灰白色点。这种罕见疾病主要影响年轻女性，估计年发病率为每10万人0.22。

Although its precise pathogenesis remains unclear, post-viral autoimmune or auto-inflammatory causes have been hypothesized3.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 status4.

虽然其确切的发病机制尚不清楚，但已经假设了病毒后自身免疫或自身炎症原因3。2020年3月，世界卫生组织（WHO）宣布，由严重急性呼吸综合征引起的2019年冠状病毒病（COVID-19）爆发冠状病毒2（SARS-CoV-2）已达到大流行状态4。

As of August 30, 2023, approximately 770 million people worldwide had developed COVID-19, including almost 34 million reported cases in South Korea5. 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.

截至2023年8月30日，全世界约有7.7亿人患有新型冠状病毒肺炎，其中包括韩国近3400万例报告病例5。为了保护个人并促进群体免疫力，美国食品和药物管理局于2020年12月授权紧急使用新型冠状病毒肺炎疫苗。

In South Korea, 86% of the population has received at least the second dose of COVID-19 vaccine6. Six COVID-19 vaccines have been authorized in Korea, ChAdOx1 nCoV-19 (Covishield™, Oxford-AstraZeneca) was first authorized on February 10, 2021, followed by BNT162b2 (Comirnaty™, Pfizer-BioNTech; March 5, 2021), Ad26.COV2.S (Jcovden™, Janssen; April 7, 2021), mRNA-1273 (Spikevax™, Moderna; May 21, 2021), NVX-CoV2373 (Nuvaxoid™, Novavax; January 12, 2022), and GBP510 (SKYCovione™, SK Bioscience; June 29, 2022).

在韩国，86%的人口至少接受了第二剂COVID-19疫苗6。韩国已经批准了六种新型冠状病毒肺炎疫苗，ChAdOx1-nCoV-19（Covishield™，Oxford AstraZeneca）于2021年2月10日首次获得批准，其次是BNT162b2（Comirnaty™，Pfizer BioNTech；2021年3月5日），Ad26.COV2.S（Jcovden™，Janssen；2021年4月7日），mRNA-1273（Spikevax™，Moderna；2021年5月21日），NVX-CoV2373（Nuvaxoid™，Novax；2022年1月12日）和GBP510（SKYCovione™，SK Bioscience；2021年1月12日）2022年6月29日）。

As of September 25, 2022, 128,710,064 doses of COVID-19 vaccines were administered: BNT162b2 (62.9%), mRNA-1273 (19.5%), ChAdOx1 (15.8%), Ad26.COV2.S (1.2%), NVX-CoV2373 (0.6%) and GBP510 (< 0.1%)7. Subsequent global efforts have effectively reduced .

截至2022年9月25日，共接种了128710064剂新型冠状病毒肺炎疫苗：BNT162b2（62.9%）、mRNA-1273（19.5%）、ChAdOx1（15.8%）、Ad26.COV2.S（1.2%）、NVX-CoV2373（0.6%）和GBP510(< 0.1%）7。随后的全球努力实际上减少了。

Table 1 Baseline characteristics of both group.Full size tableIncidence of MEWDS during pre-pandemic and pandemic periodIn 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).

表1两组的基线特征。大流行前和大流行期间MEWD的全尺寸表发病率在大流行前，有54262名患者就诊；这些患者中有0.011%被诊断出MEWDS。相比之下，大流行期间有45944名患者就诊；其中0.030%的患者被诊断出MEWDS，与大流行前相比有显著增加（p = 0.029，B = 2.756）。

The annual incidence 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).Figure 1Annual incidence (per 10,000 people) of patients with multiple evanescent white dot syndrome (MEWDS) in our hospital.

2017-2022年MEWDS患者的年发病率分别为每10000人0.73、0.75、0.78、1.32、2.49和2.07，相应的年增长率显着（p = 0.039，B = 1.316；图1）。图1我院多发性消失白点综合征（MEWDS）患者的年发病率（每10000人）。

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 incidence 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.Full size imageMEWDS cases in pandemic periodTable 2 presents the characteristics of patients with MEWDS during the pandemic period.

每年代表从指定年份的3月11日到下一年的3月10日。虚线表示COVID-19全球大流行的声明。2017-2022年，MEWDS的年发病率分别为每10000人0.73、0.75、0.78、1.32、2.49和2.07，相当于研究期间的显着增加。大流行期间的全尺寸imageMEWDS病例表2列出了大流行期间MEWDS患者的特征。

Among the 14 patients, 2 developed MEWDS within 2 weeks after COVID-19, 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, .

在这14例患者中，有2例在新型冠状病毒肺炎后2周内出现MEWD，其中包括该组中最年轻的患者（病例5；年龄13岁）。此外，该组中年龄最大的患者（78岁）在接种COVID-19疫苗后发展为MEWD。两名患者出现了MEWD的各种特征，包括9个月后出现复杂黄斑新生血管（MNV）并成功接受抗血管内皮生长因子（VEGF）治疗的病例2（图2）和双眼MEWD的病例9。

Table 2 The summary of MEWDS cases in pandemic period.Full size tableFigure 2Case 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.

表2大流行期间MEWDS病例总结。全尺寸表图2病例2，一名40岁的女性，在诊断为多发性消失白点综合征（MEWDS）后9个月出现黄斑新生血管（MNV）。（A） 眼底照相（FP）显示后极有多个灰白色病变。

(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.

（B） 荧光素血管造影（FA）显示脉络膜视网膜病变呈“环状”模式，而吲哚青绿血管造影（IA）显示晚期点的低荧光。（C） 9个月后，FP显示白点样病变消退，黄斑中心凹病变发展。

(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.Full size imageFigure 3Case 9, a 23-year-old woman, developed bacillary layer detachement (BALAD).

（D） FA显示出明显的高荧光斑点，IA显示出低荧光。（E） 光学相干断层扫描（OCT）显示视网膜下高反射材料和少量视网膜下液。（F） OCT血管造影显示明显的MNV。全尺寸图像图3Case 9，一名23岁的女性，出现了细菌层脱离（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).

（A） 第一次就诊时，眼底照相显示乳头旁区域有白色病变。（B） 光学相干断层扫描（OCT）显示BALAD伴有视网膜下液。（C） 3天后，病变扩展到周围视网膜以外，形成白点样病变，类似于多发性消失性白点综合征（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.Full size imageDiscussionThe COVID-19 pandemic has ushered in a “new normal,” significantly altering daily life and establishing new standards worldwide.

（D） OCT显示椭球区破裂。（E，F）40天后，左眼病变消失；然而，患者右眼出现类似症状，眼底镜检查出现白点样病变。全尺寸图像讨论新型冠状病毒肺炎大流行开创了一个“新常态”，极大地改变了日常生活，并在全球范围内建立了新的标准。

The pandemic has also affected the incidence and course of certain diseases. Aydin et al.16 demonstrated.

这种流行病还影响了某些疾病的发病率和病程。Aydin等[16]证明了这一点。

Data availability

数据可用性

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

在当前研究期间生成和/或分析的数据集可根据合理要求从通讯作者处获得。

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Download referencesAuthor informationAuthors and AffiliationsOnnuri Eye Hospital, #325 Baekje-daero, Jeonju, Republic of KoreaYong Yeon SongDepartment of Ophthalmology, Konyang University College of Medicine, Daejeon, Republic of KoreaJung Tae Kim, Young Suk Chang, Min-Woo Lee & Sung Chul LeeAuthorsYong Yeon SongView author publicationsYou can also search for this author in.

下载参考文献作者信息作者和附属机构Nuri眼科医院，韩国全州百济大路325号Yong Yeon Song韩国大田Konyang大学医学院眼科，韩国共和国大田Jung Tae Kim，Young Suk Chang，Min Woo Lee＆Sung Chul Lee作者Yong Yeon SongView作者出版物您也可以在中搜索这位作者。

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PubMed Google ScholarContributionsConceptualization: Y.Y.S, S.C.L Data 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.L Writing – original draft: Y.Y.S., Writing – review & editing: Y.Y.S., J.T.K., Y.S.C., M.W.L, S.C.L.Corresponding authorCorrespondence to.

PubMed谷歌学术贡献概念：Y.Y.S，S.C.L数据管理：Y.Y.S，M.W.L.形式分析：Y.Y.S.，M.W.L.调查：Y.Y.S.J.T.K，Y.S.C.监督：S.C.L，M.W.L写作-原稿：Y.Y.S.，写作-评论和编辑：Y.Y.S.，J.T.K.，Y.S.C.，M.W.L，S.C.L.对应作者。

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Reprints and permissionsAbout this articleCite this articleSong, Y.Y., Kim, J.T., Chang, Y.S. et al. Increased incidence and diverse manifestations of multiple evanescent white dot syndrome during the COVID-19 pandemic.

转载和许可本文引用本文Song，Y.Y.，Kim，J.T.，Chang，Y.S.等人在COVID-19大流行期间增加了多发性消失白点综合征的发病率和多种表现。

Sci Rep 14, 12425 (2024). https://doi.org/10.1038/s41598-024-63255-wDownload citationReceived: 13 February 2024Accepted: 27 May 2024Published: 30 May 2024DOI: https://doi.org/10.1038/s41598-024-63255-wShare this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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KeywordsMEWDSCOVID-19VaccinationIncidence

关键词Smewdscovid-19疫苗接种率

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