Rare Fundus Lesions in Patients after SARS-Cov-2 Infection: A Multicenter and Multimodal Imaging Study

Rare Fundus Lesions in Patients after SARS-Cov-2 Infection: A Multicenter and Multimodal Imaging Study | 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 Rare Fundus Lesions in Patients after SARS-Cov-2 Infection: A Multicenter and Multimodal Imaging Study Guangqi An, Bo Lei, Zhili Wang, Kaizhuan Yang, Dongsheng Fan, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4005199/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Purpose To define the characteristics of fundus manifestations in patients after SARS-Cov-2 infection with multimodal imaging techniques. Methods This is a retrospective multicenter and multimodal imaging study including 90 patients. All patients with a visual complaint occurring immediately after SARS-Cov-2 infection were referred to six clinics between December 2022 and February 2023. Demographic information and the temporal relationship between SARS-Cov-2 infection and visual symptoms were documented. The characteristics of the fundus lesions were evaluated using multimodal imaging. Results Ninety patients from six hospitals were enrolled in this study, including 24 males (26.67%) and 66 (73.33%) females. Seventy-eight patients (86.66%) (146 eyes) were diagnosed with AMN. The AMN patients were primarily young women (67.95%). Sixty-eight patients (87.18%) had AMN in both eyes. Thirty-eight eyes (24.36%) included Purtscher or Purtscher-like lesions. optical coherence tomography and infrared retinal photographs can show AMN lesions well. Eleven cases were diagnosed with simple Purtscher or Purtscher-like retinopathy (2 cases, 2.22%), VKH or VKH-like uveitis (3 cases, 3.33%), MEWDS (2 cases, 2.22%), and ROCM (5 cases, 5.56%). Conclusions After SARS-Cov-2 infection, diversified fundus lesions were evident in patients with visual complaints. In this report, AMN was the dominant manifestation, followed by Purtscher or Purtscher-like retinopathy, MEWDS, VKH-like uveitis, and ROCM. Health sciences/Diseases/Eye diseases/Eye abnormalities Health sciences/Diseases/Eye diseases/Retinal diseases Health sciences/Diseases/Eye diseases/Vision disorders Retina COVID-19 Acute macular neuroretinopathy Multimodal Imaging SARS-CoV-2 Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 1 Introduction Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a potentially fatal disease with a serious life-threatening respiratory infection and multiorgan involvement 1 . SARS-Cov-2 primarily affects the anterior segment of the eye. The most frequently reported ocular conditions include conjunctival hyperemia, chemosis, epiphora, and even frank conjunctivitis 2, 3 . It is controversial whether SARS-Cov-2 affected the retina in the early stages of the COVID-19 pandemic 4 . Since 2019, the SARS-COV-2 virus has undergone adaptive mutation that could lead to an increase in transmissibility and virulence or a change in the presentation of clinical disease 5 . The Delta variant was identified in December 2020, and the Omicron variant was identified in November 2021, both of which caused surges in the number of infections 6 . With the increasing number of COVID-19 patients, a growing number of changes have been observed in the retina and choroid 7 . In 2020, a cross-sectional study revealed retinal lesions associated with SARS-Cov-2, including dilated veins (27.7%), tortuous vessels (12.9%), retinal hemorrhages (9.25%), and cotton-wool spots (7.4%) 8 . A review in 2022 suggested the potential involvement of the posterior segment in SARS-Cov-2, either in the initial or later stage 9 . However, few studies have systematically described the manifestations of the posterior segment of the eye by multimodal imaging study 10 . Due to the lockdown policy was suddenly lifted, there was a surge in the number of Omicron infections in Chinese people from late December 2022 to late January 2023 in China 11 . Based on the large number of SARS-Cov-2 infected patients, it was possible for us to observe a series of patients with rare fundus Lesions after SARS-Cov-2 infection. These rare fundus lesions with a large increase over the same period of the previous year may be related to SARS-Cov-2 infection. Because these lesions are rare and often lead to misdiagnosis, reasonable examination methods can help us quickly identify lesions and diagnose them. In the present case series, multimodality imaging was used to describe retinal and/or choroidal conditions that could be associated with SARS-Cov-2 infections. We outlined the features of retinal and choroidal manifestations following SARS-Cov-2 infections and clarified the best diagnostic methods to improve our understanding of their pathogenesis and diagnosis. 2 Materials and Methods 2.1 Participants This was a cross-sectional multicenter and multimodal imaging study. From December 2022 to February 2023, 90 patients were identified with retinal and/or choroidal conditions associated with COVID‑19 infection in six clinics, including the First Affiliated Hospital of Zhengzhou University and/or Zhengzhou University People’s Hospital and/or The Second People's Hospital of Zhengzhou and/or Luoyang Central Hospital Affiliated to Zhengzhou University and/or Nanyang Eye Hospital, Nanyang and/or The First Affiliated Hospital of Nanyang Medical College. The incidence of these diseases in the same period of the previous year was collected from the outpatient information databases of those hospitals All patients tested positive by real‑time reverse transcription‑polymerase chain reaction (RT‑PCR) and/or antigen detection for SARS‑CoV‑2 from pharyngeal or nasopharyngeal swabs during the active phase of SARS‑CoV‑2 infection and eye symptoms occurred whitin one month after SARS‑CoV‑2 infection. Patients who were not infected with SARS‑CoV‑2 and whose ocular symptoms occurred more than one month after SARS‑CoV‑2 infection were excluded. This study was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University [2023-KY-0637]. Based on the Declaration of Helsinki , we collected demographic information, SARS‑CoV‑2 infection symptoms, chief complaints and other clinical examination results after informed consent was signed by the patients or their guardians. The clinical examination results included slit‑lamp examination and indirect ophthalmoscopy results, best corrected visual acuity (BCVA), spherical equivalent (SE), fundus photo images, visual field analysis (VF), infrared retinal photographs (IR), optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), multifocal electrophysiology (mf ERG), fundus autofluorescence (FAF) and adaptive optics (AO). All patients were diagnosed and recorded by 2 doctors individually. In cases of disagreement, the senior ophthalmologist made the final decision. 2.2 Method of Eye Examination All outpatients were examined by slit‑lamp and ophthalmoscopy. BCVA and SE were tested by optometrists. Fundus photos and FAF were taken using an ultrawide field fundus camera (Daytona P200T, Optomap, UK) and fundus camera (CLARUS 500 v1.1, Carl Zeiss Co. Ltd., Germany). mf ERG (RETI-scan multifocal ERG (Roland Consult, Germany) was performed on the patients. VF examination (Humphrey Field Analyzer 3, Carl Zeiss Co. Ltd., Germany) or micro examination (MP3-microperimerter Ver.1.2.1, NIDEK Co. Ltd., Japan) was selected according to the patient's symptoms. Skilled ophthalmologists performed swept source OCT (SS-OCT) (VG200 or VG100, SVision, China) or spectral domain OCT (SD-OCT) (Spectralis OCT, Heidelberg Engineering GmbH, Germany), which included stars in 16 or 32 lines and multiline scanning with a scan line length of 10 to 16 mm. SS-OCTA scanning was performed with a scan square of 6 mm×6 mm or 12 mm×12 mm. The depth of the scanning was 3 to 6 mm. The scanning laser wavelength was 1050 nm or 870 nm. IR images were taken by a 40°×40° confocal scanning superluminescent (diode) ophthalmoscope (cSSO) with a wavelength of 820 nm or confocal scanning laser ophthalmoscope (cSLO) with a wavelength of 810 nm. FFA and ICGA (Spectralis HRA, Heidelberg Engineering GmbH, Germany) were performed to observe vascular lesions. AO (rtx1, Imagine Eyes, Orsay, France) was performed to clarify the status of the optic cone optic rod cells. 2.3 Statistical Analysis SPSS statistics 26.0 software (IBM Corp.; USA) were used to analyze the data. Categorical data are described using frequencies and percentages. The Kolmogorov‒Smirnov test was performed to verify whether all the data sets were distributed normally. Continuous variables with a normal distribution are presented as the mean ± standard deviation (SD), and a t test was used for comparisons. Nonnormal variables are reported as medians (interquartile ranges). A P value less than or equal to 0.05 was considered statistically significant. 3. Results 3.1 COVID-19 infection, vaccination history and demographics of patients Ninety patients were included in this study, including 24 males (26.67%) and 66 (73.33%) females. Their age was 31 ± 15 years old with a range of 10 to 85 years (Table 1). All patients had a history of COVID-19 infection. Visual symptoms occurred 0 days to 30 days after the onset of fever, dry cough, malaise, etc. The mean interval between COVID-19 infection and visual symptom onset was 2 ( 2 , 3 ) days. Five patients had diabetes, six patients had kidney disease, four patients had hypertension. Tabel.1 COVID-19 history and demographics of patients Disease Number of cases (male cases) n = 90 (34, 37.78%) Age Visual symptoms occurred after COVID-19 symptoms Combined with Purtscher-like retinopathy Acute macular neuroretinopathy 78 (22, 28.21%) 29 ± 11 yrs. 0 to 20 days Average 2( 2 , 3 ) 17 Multiple evanescent white-dot syndrome 2(1, 50.00%) 22 and 37 yrs. respectively 5 days 0 Vogt-Koyanagi-Harada syndrome-like uveitis 3(0, 0.00%) 34,43 and 49 yrs. respectively 4,5 and 7 days respectively 0 Rhino-orbital-cerebral mucormycosis 5(1, 20.00%) 70 ± 15 5 to 30 days Average 14 ± 10 days 2 We reviewed the detailed COVID-19 infection history, medication history and vaccination history in 33 of the 90 patients. All patients had a fever of 37.5 to 40℃. Among them, 24 patients (71.88%) took ibuprofen, acetaminophen or Tylenol to reduce fever, whereas 9 (28.125%) did not. Twelve patients (36.37%) were dehydrated (sweating profusely and unable to drink) prior to the onset of symptoms, while 20 patients (63.63%) were dehydrated. Seven patients (21.21%) received 2 doses of inactivated COVID-19 vaccine, 19 patients (57.58%) received 3 doses of inactivated COVID-19 vaccine, and 7 patients (21.21%) did not receive inactivated COVID-19 vaccine. 3.2 Clinical Characteristics of Our Case Series and Multimodal Imaging Among all patients, 78 (86.66%) were diagnosed with acute macular neuroretinopathy (AMN). The remaining 12 patients were diagnosed with simple Purtscher-like retinopathy (2 patients, 2.22%), Vogt‒Koyanagi‒Harada-like (VKH-like) uveitis (3 patients, 3.33%), multiple evanescent white-dot syndrome (MEWDS) (2 patients, 2.22%), and rhino-orbital-cerebral mucormycosis (ROCM) (5 patients, 5.56%). However, in December 2021 to February 2022 year, there were only one Purtscher retinopathy patient with chest trauma, one ROCM patient and two AMN patients. Although there are as many as 21 patients first diagnosed as VKH, their clinical symptoms are different from those after SARS-Cov-2 infection. The number of MEWDS patient cannot obtain because MEWDS does not have an ICD diagnostic code. 3.2.1 Acute Macular Neuroretinopathy (AMN) and Purtscher or Purtscher-like Retinopathy A total of 78 patients (146 eyes) were diagnosed with AMN, including 22 males (28.21%) and 56 (71.79%) females. Their age was 29 ± 11 years old with a range of 10 to 64 years old. The majority of patients were young women (67.95%). There was no statistically significant difference in age between the sexes ( t = -0.22, P = 0.830). Their complaints were "black shadows or dark spots in front of the eyes or visual field defects" (38 cases, 48.72%) and "blurred vision. "(40 cases, 51.28%). Ten patients (12.82%) had visual problems in one eye. Sixty-eight patients (87.18%) had visual problems in both eyes. The BCVA of the 146 diseased eyes was 0.13 (0.00, 0.63) logMAR with a range of 0.00 to 2.00 Log MAR. In a total of 146 eyes with AMN, the BCVAs at presentation were generally well documented to be 0.30 LogMAR or better (96 eyes, 65.75%). 1.00 LogMAR or worse in 18 eyes (12.33%). Nineteen cases (38 eyes) of 78 cases (146 eyes) (24.36%, 26.03%) combined cotton-wool spots or Purtscher-like retinopathy at the initial visit (Fig. 3 A). Ten of these patients (52.63%) had kidney disease or hypertension. OCT with IR were used in 146 eyes (100.00%), and in each IR image, AMN lesions were dark or gray with well-demarcated margins with oval (Fig. 1B1), petal-shaped (Fig. 1C1), multifocal dark spots (Fig. 1D1). AMN lesions on OCT exhibited one or more abnormal characteristics, including outer retinal hyperreflectivity (Fig. 1B3 4 yellow arrowhead), ellipsoid zone loss (Fig. 1C3 yellow arrows), small cavity in macular (Fig. 2B1 yellow arrowhead) and thinning of the outer nuclear layer (ONL) (Fig. 1D3 yellow arrowhead). Fundus photos were taken in 57 of 146 eyes. The lesions showed wedge-shaped petal-shaped, oval slightly dark areas in 16 eyes (28.07%) (Fig. 3A1, A2 white arrowheads). The contrast sensitivity of the fundus photo was not as good as that of IR and OCT. Ten eyes underwent mf ERG and all showed one to several abnormal findings, including diminished amplitudes and diminished implicit time (Fig. 3A1, A2 white arrowheads). Thirty-six eyes with AMN experienced one to several paracentral scotomas by Amsler grid, VF or micro-VF testing. The mf ERG and VF specialty corresponded closely to the shape and location of the clinical lesion (Fig. 3F1, F2). The shape of VF abnormalities was wedge-shaped, boot-shaped, and round-shaped. Four eyes underwent AO and showed small patches of cone rod cell loss in the area corresponding to the lesions (Fig. 2D1, D2 yellow boxes). 3.2.2 VKH-like uveitis and Multiple Evanescent White-Dot Syndrome (MEWDS) A 49-year-old female patient complained of "visual distortion in both eyes accompanied by tinnitus." Her right and left BCVAs were 0.52 and 1.3 Log MAR, respectively. After fever, she was diagnosed with SARS-Cov-2 infection via an antigen test. She went to the hospital after developing hazy vision in her left eye five days later. After a month, her right eye also appeared blurry, so she sought medical attention. Both eyes had congested conjunctiva and adherent irises; the vitreous was cloudy, and the fundus was not visible. (Fig. 4A1, A2). We administered prednisone (60 mg once a day), tobramycin dexamethasone eye drops (1 drop every 4 hours), and 0.1% atropine eye ointment (1 drops twice a day). Three days later, symptoms of the anterior segment were reduced, and the fundus was visible (Fig. 4D1, D2). OCT showed neuroepithelial detachment (Fig. 4E1, E2). After 10 days, the BCVA of her right and left eyes improved to 0.22 and 0.30 LogMAR, respectively, and the neuroepithelial detachment diminished. Another 43-year-old female complained of "blurred vision on both eyes without headache and tinnitus." The BCVAs in both eyes were 0.10 LogMAR 4 days after fever caused by SARS-Cov-2. We applied FFA and OCT to her eyes (Fig. 4 F, G). We diagnosed her with VKH-like uveitis and administered prednisone (60 mg once a day) and 0.1% atropine eye ointment (1 drop twice a day). She felt better, and the BCVAs improved to 0.00 LogMAR in both eyes seven days later. FFA and OCT showed that neuroepithelial detachment was reduced and eliminated with time (Fig. 4G1, G2). She only received one month of hormone treatment and did not relapse for half a year. These two patients didn’t have headache or tinnitus or skin/hair change. They were highly sensitive to glucocorticoids, had good visual prognoses, and didn’t relapse in a short time after discontinuation of glucocorticoids. These were different from the classic VKH syndrome, so we named it VKH-like uveitis. A 21-year-old male patient was diagnosed with MEWDS and complained of "blurred vision on the left eye" five days after a fever caused by SARS-Cov-2. The BCVAs were 0.00 and 0.10 LogMAR in his right and left eyes. Some yellow-white punctate lesions were faintly seen on fundus photography (Fig. 5 A2), OCT showed that there were structural abnormalities in the outer retina (Fig. 5 C2). The mf ERG showed that the visual sensitivity of the patient's left eye was reduced (Fig. 5 D2). There were some highly fluorescent lesions on the FAF (Fig. 5 B2). F) and scattered high fluorescence spots on FFA (Fig. 5 . B2). However, the patient did not undergo ICGA due to drug allergies. We suggested that the patient should return to the clinic two weeks later, but he did not return. Then, we performed a telephone follow-up and were informed that his symptoms had been eliminated. Another 37-year-old female had similar symptoms. 3.2.3 Rhino-orbital-cerebral Mucormycosis (ROCM) A 49-year-old male patient with SARS-Cov-2-related pneumonia had recurrent fever for 20 days and underwent "intracranial hematoma drainage" because of "diabetic ketoacidosis and cerebral hemorrhage." Then, he developed swelling on the right side of the face 3 days later. Sooner afterward, he suddenly lost vision in his right eye. This patient had a history of high blood pressure and diabetes but did not take medications regularly. Due to fever and infection, his vital signs were unstable, and his right eye was not treated (Fig. 6 B). B1). Pale retinal and “cherry erythema” suggested central retinal artery occlusion (CRAO). Fungal cultures of nasal tissue in patients showed wide septum hyphae, which was characteristic of Mucormyces. This confirmed that he had ROCM. The patient's right eyeball was fixed in the upper right position and could only be slightly moved up and down instead of left and right (Fig. 6 B). A). Unfortunately, the optic disc of the right eye was pale (Fig. 6 B). Interestingly, we observed cotton-wool spots around the optic disc of the left eye (Fig. 6 B2). B3). OCT showed retinal-choroidal atrophy and interlaminar edema in his right eye (Fig. 6 B). C1). The cotton-wool patch showed thickening of the neuroepithelium (Fig. 6 B). C3). The patient's magnetic resonance imaging (MRI) showed abnormal signals in the right orbital tip (Fig. 6 B). D). Another 49-year-old female patient was also diagnosed with ROCM. She also had diabetic ketoacidosis, which suggested poor glycemic control. Similarly, she lost her vision in her right eye. Fundus photographs showed cotton-wool spots and bleeding on her left eye as well (Fig. 6 E). Blood tests showed that her white blood cells were 13.68 (reference 3.5–9.5) 10^9/L, neutrophil percentage was 83.5% (reference 40–75%), DD-dimer was as high as 10.79 (reference 0-0.3) mg/L (DDU), fibrinogen degradation products (FDP) were as high as 10.79 (reference 0–5) mg/L, and C-reactive protein (CRP) and procalcitonin (PCT) and interleukin 6 (IL-6) were more than 5 times the normal value. Both patients were not treated because their vision was no light projection (NLP). In addition, three other female patients aged 77, 81, and 85 years who had ROCM and diabetes underwent eye removal. 4 Discussion Since the COVID-19 pandemic in November 2019, over 757 million confirmed cases and over 6.8 million deaths have been reported around the world 12 . SARS-CoV-2 infects host cells through the transmembrane spike protein (S protein), which in turn infects human endothelial cells with ACE2 as its receptor, so tissues with ACE2 receptors are susceptible to SARS-CoV-2 infection 13 . ACE2 is widely expressed in endothelial cells of the lung, blood vessels, heart, kidney, small intestine and other tissues and organs, with a small amount of expression in the liver and nose. The above organs are vulnerable to damage after infection with SARS-CoV-2 14, 15 . Moreover, ACE2 is a major converting enzyme in the vascular protective axis of the renin-angiotensin system in the retina, and its downregulation may lead to retinal ischemia, which is related to microangiopathy, retinitis, and retinal degeneration 15–17 . Previous literature has reported retinal and choroidal manifestations that may be associated with SARS-CoV-2 as shown in Table 2. Depending on the pathological mechanism, we classify it as noninfectious or infectious. Noninfectious manifestations may be related to ischemia or inflammation. RVO and RAO are common diseases in ophthalmology, and patients often have underlying diseases such as diabetes and hypertension 18, 19 . Therefore, these diseases were not included in our case series as fundus lesions related to SARS-CoV-2. However, uncommon eye diseases such as AMN and ROCM have increased in incidence alongside the rise in SARS-CoV-2 infection rates 20, 21 . Tabel.2 Retinal and choroidal manifestations in patients after SARS-CoV-2 infection Type of the manifestations Clinical findings / Disease No-infectious Retinal vein occlusion (RVO) 14, 15 Retinal artery occlusion (RAO) 16 Purtscher-like retinopathy 17 Cotton-wool spots 18 Isolated hemorrhages 19 Acute macular neuroretinopathy (AMN) 20 Paracentral acute middle maculopathy (PAMM) 21 Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) 22 Multiple evanescent white-dot syndrome (MEWDS) * Serpiginous choroiditis (SC) 23 Optic neuritis (ON) 24 Vogt-Koyanagi-Harada syndrome-like uveitis 25 Central serous chorioretinopathy (CSCR) 26 Infectious Endogenous endophthalmitis (Bacterial / Fungal) 27 Acute retinal necrosis (ARN) 28 Rhino-orbital-cerebral mucormycosis (ROCM) 29 4. 1 Acute macular neuroretinopathy (AMN) and Purtscher or Purtscher-like retinopathy We observed this case series with SARS-CoV-2-related retinal and choroidal manifestations. Typically, the patient was a young woman who developed visual impairment two days following the onset of infection symptoms. As the standard, with the relationship of cause, trigger and disease, our results suggested a close relationship between the emergence of AMN or Purtscher or Purtscher-like retinopathy and SARS-CoV-2 infection. AMN is a relatively rare disorder involving transient or permanent central or paracentral scotomas 39 . It is characterized by dark, reddish-brown macular lesions and corresponds precisely to visual field abnormalities 40 . AMN has been reported to occur in several different clinical settings. The majority of patients are women in their reproductive years who develop symptoms in association with oral contraceptives, hypotension, viral illness, intravitreous injection, vaccination and sympathomimetic agents (epinephrine, caffeine). 3, 41–47 . Since the syndrome was initially characterized by Bos and Deutmann 48 in 1975, the pathophysiology of AMN has been the subject of intense discussion, especially in light of the disorder's diverse causes. Acute retinal lesions are characterized by faint retinal translucency on bio microscopy and hyperreflectivity in the outer plexiform and outer nuclear layers on OCT. FFA and ICGA do not reveal any retinal or choroidal vascular leakage, perfusion deficits or transmission defects. mfERG testing shows reduced amplitudes within the scotomatous areas 49 . Evolution of macular lesions is characterized by resolution within several days of the initial retinal translucency and hyperreflectivity, followed by the development of reddish-brown lesions that appear dark on IR and show thinning of the outer nuclear layer and attenuation or loss of the ellipsoid and interdigitation zones on OCT. Compared to FFA, ICGA and FAF, OCT and IR images display the lesions of AMN more effectively. The cSSO fundus photography used in this study is a laser with a wavelength of 820 nm; it is also an IR imaging approach in essence. Due to the destruction of the elliptical zone, the laser is absorbed by the deeper and stronger retinal epithelium, demonstrating the essence of shadow and OCT is optical coherence imaging, and the areas with mixed or dense tissue structure will show high reflection 50 . From the perspective of imaging alone, the morphology of hyper reflex in the early stage of the onset of AMN was consistent with that of the fiber of the cone and rod cells, which indicates the affected site (Fig. 1 A) 40, 47 . At present, the generation of AMN is mainly dominated by two theories: the inflammation-related immune theory and the vascular-related ischemia and hypoxia theory 49, 51 . This needs to be discussed in combination with vascular parameters, and our research team will explore in future research. 4. 2 VKH-like uveitis and Multiple Evanescent White-Dot Syndrome (MEWDS) VKH disease is an immune-mediated disorder characterized by bilateral uveitis frequently associated with neurological (meningeal), auditory, and integumentary symptoms. Auditory manifestations (tinnitus, hearing loss and vertigo) and others (including headache, neck and back stiffness) usually occur before or concurrently with ocular involvement 52 . A previous study linked VKH to SARS-CoV-2 Vaccines 53 . The VKH-like patients in this series responded favorably to corticosteroid therapy. Whether SARS-CoV-2 is a precipitating factor or a disease inducer will require longer-term observation. MWDES is related to colds and viral infections. Both patients in this study developed symptoms five days after experiencing SARS-CoV-2-related fever, which is considered a cause. 4.3 Rhino-orbital-cerebral Mucormycosis (ROCM) ROCM can be a serious complication of severe SARS-CoV-2 infection, particularly in patients with uncontrolled diabetes. The risk factors predisposing patients to ROCM are uncontrolled diabetes, neutropenia, hematological malignancies, organ transplantation, trauma and burn, and use of immunosuppressants such as corticosteroids 37, 38 . Patients were often blinded by mucormycosis invasion of the orbital apex leading to orbital apex syndrome forming retinal artery obstruction. This disease is easily misdiagnosed due to its reputation as a difficult-to-treat mold infection and its high mortality in patients with SARS-CoV-2 infection, particularly those with pulmonary disease. A careful management plan can be successful for rhino-orbital cerebral disease if there is early diagnosis of infection and control of infection 54 . In conclusion, the retinal and choroidal conditions after SARS-CoV-2 infection are diverse, including AMN, MEWDS, VKH-like uveitis, and ROCM. Multimodal imaging may be used to evaluate the lesions from the anatomical and functional levels, and an appropriate examination with multimodal imaging is beneficial for patient management and follow-up. Declarations Acknowledgments This work was supported by National Natural Science Foundation of China [819707922 and 82171040] and Medical Science and Technology Project of Health Commission of Henan Province [YXKC2020026]. The authors would like to thank Dr. Kang Chen for providing us free mf ERG test and thank Dr. Yubao Zheng in Nanyang Eye Hospital, Dr. Ming Hou in Luoyang Central Hospital Affiliated to Zhengzhou University, Dr. Jing Wng, Dr. Zhenzhen Liu in The First Affiliated Hospital of Zhengzhou University and Dr. Shiqing Li, Dr. Qingge Guo, Dr. Xiao Chen, Dr. Xiaohong Guo, Dr. Changgeng Liu in Henan Eye Hospital for providing us fundus photos, OCT and FFA images Contributions Conception and design: An, Du, Jin Data collection: An, Wang, Yang, Fan, Li, Fu, Fang, Zhang, Zhao, Chen Analysis and interpretation: An Obtained funding: Lei, Du, Jin Overall responsibility: An, Wang, Li, Lei, Du, Jin Disclosures: There are no financial conflicts of interest to disclose. References Sharma A, Tiwari S, Deb MK, Marty JL. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): a global pandemic and treatment strategies. Int J Antimicrob Agents. Aug 2020;56(2):106054. doi: 10.1016/j.ijantimicag.2020.106054 Costa IF, Bonifacio LP, Bellissimo-Rodrigues F, et al. Ocular findings among patients surviving COVID-19. Sci Rep. May 26 2021;11(1):11085. doi: 10.1038/s41598-021-90482-2 Sen M, Honavar SG, Sharma N, et al.COVID-19 and Eye: A Review of Ophthalmic Manifestations of COVID-19. Indian J Ophthalmol. Mar 2021;69(3):488–509. doi: 10.4103/ijo.IJO_297_21 Karampelas M, Dalamaga M, Karampela I. Does COVID-19 Involve the Retina? Ophthalmol Ther. Sep 21 2020:1–3. doi: 10.1007/s40123-020-00299-x Harvey WT, Carabelli AM, Jackson B, et al. SARS-CoV-2 variants, spike mutations and immune escape. Nat Rev Microbiol. Jul 2021;19(7):409–424. doi: 10.1038/s41579-021-00573-0 Aleem A, Akbar Samad AB, Slenker AK. Emerging Variants of SARS-CoV-2 And Novel Therapeutics Against Coronavirus (COVID-19). StatPearls. 2022. Jevnikar K, Jaki Mekjavic P, Vidovic, et al.An Update on COVID-19 Related Ophthalmic Manifestations. Ocul Immunol Inflamm. May 19 2021;29(4):684–689. doi: 10.1080/09273948.2021.1896008 Invernizzi A, Torre A, Parrulli S, et al. Retinal findings in patients with COVID-19: Results from the SERPICO-19 study. EClinicalMedicine. Oct 2020;27:100550. doi: 10.1016/j.eclinm.2020.100550 Zhang Y, Stewart JM. Retinal and choroidal manifestations of COVID-19. Curr Opin Ophthalmol. Nov 1 2021;32(6):536–540. doi: 10.1097/ICU.0000000000000801 McGrath OE, Aslam TM. Use of Imaging Technology to Assess the Effect of COVID-19 on Retinal Tissues: A Systematic Review. Ophthalmol Ther. Jun 2022;11(3):1017–1030. doi: 10.1007/s40123-022-00509-8 Pan Y, Wang L, Feng Z, et al. Characterisation of SARS-CoV-2 variants in Beijing during 2022: an epidemiological and phylogenetic analysis. Lancet. Feb 25 2023;401(10377):664–672. doi: 10.1016/S0140-6736(23)00129-0 https:// . Updated 2023.02.05. Jackson CB, Farzan M, Chen B, et al.Mechanisms of SARS-CoV-2 entry into cells. Nat Rev Mol Cell Biol. Jan 2022;23(1):3–20. doi: 10.1038/s41580-021-00418-x Guney C, Akar F. Epithelial and Endothelial Expressions of ACE2: SARS-CoV-2 Entry Routes. J Pharm Pharm Sci. 2021;24:84–93. doi: 10.18433/jpps31455 Pagliaro P, Thairi C, Alloatti G, et al. Angiotensin-converting enzyme 2: a key enzyme in key organs. J Cardiovasc Med (Hagerstown). Jan 1 2022;23(1):1–11. doi: 10.2459/JCM.0000000000001218 Yener AU. COVID-19 and the Eye: Ocular Manifestations, Treatment and Protection Measures. Ocul Immunol Inflamm. Aug 18 2021;29(6):1225–1233. doi: 10.1080/09273948.2021.1977829 Lumbers ER, Head R, Smith GR, et al. The interacting physiology of COVID-19 and the renin-angiotensin-aldosterone system: Key agents for treatment. Pharmacol Res Perspect. Feb 2022;10(1):e00917. doi: 10.1002/prp2.917 Hayreh SS, Podhajsky PA, Zimmerman MB. Retinal artery occlusion: associated systemic and ophthalmic abnormalities. Ophthalmology. Oct 2009;116(10):1928–36. doi: 10.1016/j.ophtha.2009.03.006 Modjtahedi BS, Do D, Shaw J. Correspondence Regarding Changes in the Incidence of Retinal Vascular Occlusions After COVID-19 Diagnosis-Reply. JAMA Ophthalmol. Nov 1 2022;140(11):1143–1144. doi: 10.1001/jamaophthalmol.2022.3479 Azar G, Bonnin S, Vasseur V, et al. Did the COVID-19 Pandemic Increase the Incidence of Acute Macular Neuroretinopathy? J Clin Med. Oct 28 2021;10(21)doi: 10.3390/jcm10215038 Nehara HR, Kumawat S, Gupta J, et al. Coronavirus Disease, Diabetes and Glucocorticoid a Terrible Trio for Invasive Mucormycosis: An Observational Study from Northwest Rajasthan. J Assoc Physicians India. Dec 2022;69(12):11–12. Nourinia R, Ghassempour M, Ahmadieh H, Abtahi SH. Branch retinal vein occlusion after COVID-19. J Fr Ophtalmol. Oct 2021;44(8):e441-e443. doi: 10.1016/j.jfo.2021.06.003 Cuadros Sanchez C, Eguen CS, Gutierrez-Ezquerro R, et al. Central Retinal Vein Occlusion Presumably Associated with Lupus Anticoagulant Induced by SARSCoV-2. Ocul Immunol Inflamm. Oct-Nov 2022;30(7–8):2010–2013. doi: 10.1080/09273948.2021.1933077 Au SCL, Ko CKL. Central Retinal Artery Occlusion in Patients with COVID-19: Imaging for Underlying Causes. Radiology. Jul 2021;300(1):E315. doi: 10.1148/radiol.2021210479 Thatcher MD, Wu LZ, Varma R. Bilateral Purtscher-Like Retinopathy Associated With COVID-19 Infection. JAMA Ophthalmol. Feb 9 2023;doi: 10.1001/jamaophthalmol.2022.6255 Chan AX, Ritter M, Bakhoum MF. Bilateral cotton wool spots after ambulatory COVID-19. Int J Infect Dis. Apr 2021;105:414–415. doi: 10.1016/j.ijid.2021.02.119 Pereira LA, Soares LCM, Nascimento PA, et al. Retinal findings in hospitalised patients with severe COVID-19. Br J Ophthalmol. Jan 2022;106(1):102–105. doi: 10.1136/bjophthalmol-2020-317576 Giacuzzo C, Eandi CM, Kawasaki A. Bilateral acute macular neuroretinopathy following COVID-19 infection. Acta Ophthalmol. Mar 2022;100(2):e611-e612. doi: 10.1111/aos.14913 Castro CS, Ferreira AS, Silva NP, et al.Paracentral Acute Middle Maculopathy After COVID-19 Disease: Multimodal Evaluation. Retin Cases Brief Rep. Jul 15 2022;doi: 10.1097/ICB.0000000000001301 Fischer NA, Wann RC, Crosson JN. Acute posterior multifocal placoid pigment epitheliopathy following COVID-19 infection. Am J Ophthalmol Case Rep. Mar 2023;29:101790. doi: 10.1016/j.ajoc.2022.101790 Providencia J, Fonseca C, Henriques F, et al.Serpiginous choroiditis presenting after SARS-CoV-2 infection: A new immunological trigger? Eur J Ophthalmol. Jan 2022;32(1):NP97-NP101. doi: 10.1177/1120672120977817 Landecho MF, Yuste JR, Gandara E, et al. COVID-19 retinal microangiopathy as an in vivo biomarker of systemic vascular disease? J Intern Med. Jan 2021;289(1):116–120. doi: 10.1111/joim.13156 Yepez JB, Murati FA, Petitto M, et al. Vogt-Koyanagi-Harada Disease Following COVID-19 Infection. Case Rep Ophthalmol. Sep-Dec 2021;12(3):804–808. doi: 10.1159/000518834 Mohd-Alif WM, Nur-Athirah A, Hanapi MS, Tuan Jaffar TN, Shatriah I. Bilateral and Multiple Central Serous Chorioretinopathy Following COVID-19 Infection: A Case Report and Literature Review. Cureus. Mar 2022;14(3):e23246. doi: 10.7759/cureus.23246 Agarwal M, Sachdeva M, Pal S, et al. Endogenous Endophthalmitis A Complication of COVID-19 Pandemic: A Case Series. Ocul Immunol Inflamm. May 19 2021;29(4):726–729. doi: 10.1080/09273948.2021.1945111 Nishiyama T, Tsujinaka H, Mizusawa Y, et al. Acute retinal necrosis in a patient on immunosuppressive treatment for COVID-19 pneumonia: a case report. BMC Ophthalmol. Nov 30 2022;22(1):462. doi: 10.1186/s12886-022-02692-5 Kaur R, Khan B, Sharma A. Optical Coherence Tomography of Retinal Artery Occlusion Associated With Mucormycosis and COVID-19. JAMA Ophthalmol. Nov 1 2021;139(11):e214064. doi: 10.1001/jamaophthalmol.2021.4064 Dubey S, Mukherjee D, Sarkar P, et al. COVID-19 associated rhino-orbital-cerebral mucormycosis: An observational study from Eastern India, with special emphasis on neurological spectrum. Diabetes Metab Syndr. Sep-Oct 2021;15(5):102267. doi: 10.1016/j.dsx.2021.102267 Hufendiek K, Gamulescu MA, Hufendiek K, et al. Classification and characterization of acute macular neuroretinopathy with spectral domain optical coherence tomography. Int Ophthalmol. Dec 2018;38(6):2403–2416. doi: 10.1007/s10792-017-0742-9 Fawzi AA, Pappuru RR, Sarraf D, et al. Acute macular neuroretinopathy: long-term insights revealed by multimodal imaging. Retina. Sep 2012;32(8):1500–13. doi: 10.1097/IAE.0b013e318263d0c3 Fekri S, Khorshidifar M, Dehghani MS, et al.Acute macular neuroretinopathy and COVID-19 vaccination: Case report and literature review. J Fr Ophtalmol. Jan 2023;46(1):72–82. doi: 10.1016/j.jfo.2022.09.008 Powers JH, Singh PP, Grewal DS, et al. Multimodal imaging of type 2 acute macular neuroretinopathy in a young woman. Digit J Ophthalmol. 2021;27(3):44–47. doi: 10.5693/djo.02.2021.06.004 Gupta N, Padidam S, Tewari A. Acute macular neuroretinopathy (AMN) related to energy drink consumption. BMJ Case Rep. Dec 15 2019;12(12)doi: 10.1136/bcr-2019-232144 Ashfaq I, Vrahimi M, Waugh S, et al. Grinton ME, Browning AC. Acute Macular Neuroretinopathy Associated with Acute Influenza Virus Infection. Ocul Immunol Inflamm. Feb 17 2021;29(2):333–339. doi: 10.1080/09273948.2019.1681470 Dutta Majumder P, Agarwal A. Acute Macular Neuroretinopathy and Paracentral Acute Middle Maculopathy during SARS-CoV-2 Infection and Vaccination. Vaccines (Basel). Feb 17 2023;11(2)doi: 10.3390/vaccines11020474 Radwan LM, Bou Ghanem GO, Daye GN, et al.Acute macular neuroretinopathy associated with intravitreal anti-VEGF injection: A case report. Am J Ophthalmol Case Rep. Dec 2022;28:101687. doi: 10.1016/j.ajoc.2022.101687 Guardiola GA, Villegas VM, Cruz-Villegas V, et al.Acute macular neuroretinopathy in dengue virus serotype 1. Am J Ophthalmol Case Rep. Mar 2022;25:101250. doi: 10.1016/j.ajoc.2021.101250 Bos PJ, Deutman AF. Acute macular neuroretinopathy. Am J Ophthalmol. Oct 1975;80(4):573–84. doi: 10.1016/0002-9394(75)90387-6 Bhavsar KV, Lin S, Rahimy E, et al. Acute macular neuroretinopathy: A comprehensive review of the literature. Surv Ophthalmol. Sep-Oct 2016;61(5):538–65. doi: 10.1016/j.survophthal.2016.03.003 Lains I, Wang JC, Cui Y, et al. Retinal applications of swept source optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). Prog Retin Eye Res. Sep 2021;84:100951. doi: 10.1016/j.preteyeres.2021.100951 Kulikov AN, Maltsev DS, Leongardt TA. Retinal Microvasculature Alteration in Paracentral Acute Middle Maculopathy and Acute Macular Neuroretinopathy: A Quantitative Optical Coherence Tomography Angiography Study. Retin Cases Brief Rep. Fall 2020;14(4):343–351. doi: 10.1097/ICB.0000000000000709 Du L, Kijlstra A, Yang P. Vogt-Koyanagi-Harada disease: Novel insights into pathophysiology, diagnosis and treatment. Prog Retin Eye Res. May 2016;52:84–111. doi: 10.1016/j.preteyeres.2016.02.002 Chen X, Li X, Li H, et al. Ocular Adverse Events after Inactivated COVID-19 Vaccination in Xiamen. Vaccines (Basel). Mar 21 2022;10(3)doi: 10.3390/vaccines10030482 Hoenigl M, Seidel D, Carvalho A, et al. The emergence of COVID-19 associated mucormycosis: a review of cases from 18 countries. Lancet Microbe. Jul 2022;3(7):e543-e552. doi: 10.1016/S2666-5247(21)00237-8 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 20 May, 2024 Reviews received at journal 08 May, 2024 Reviews received at journal 01 May, 2024 Reviewers agreed at journal 27 Apr, 2024 Reviewers agreed at journal 27 Apr, 2024 Reviewers agreed at journal 19 Apr, 2024 Reviewers invited by journal 19 Apr, 2024 Editor assigned by journal 17 Apr, 2024 Editor invited by journal 18 Mar, 2024 Submission checks completed at journal 15 Mar, 2024 First submitted to journal 01 Mar, 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4005199","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":281090153,"identity":"f5e103d9-1952-450c-ab4a-2f6acc1bab4b","order_by":0,"name":"Guangqi An","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Guangqi","middleName":"","lastName":"An","suffix":""},{"id":281090154,"identity":"b6a019e2-552e-4075-ada8-2a77b8f09e12","order_by":1,"name":"Bo Lei","email":"","orcid":"","institution":"Zhengzhou University People’s Hospital, Henan Eye Hospital \u0026 Henan Eye Institute, Henan Provincial People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Bo","middleName":"","lastName":"Lei","suffix":""},{"id":281090155,"identity":"e8444b8c-d1d8-4b1e-825c-9578397a783c","order_by":2,"name":"Zhili Wang","email":"","orcid":"","institution":"Zhengzhou University People’s Hospital, Henan Eye Hospital \u0026 Henan Eye Institute, Henan Provincial People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zhili","middleName":"","lastName":"Wang","suffix":""},{"id":281090156,"identity":"7533de33-9e67-46b5-93e4-82b5cc57b4bb","order_by":3,"name":"Kaizhuan Yang","email":"","orcid":"","institution":"The Second People's Hospital of Zhengzhou","correspondingAuthor":false,"prefix":"","firstName":"Kaizhuan","middleName":"","lastName":"Yang","suffix":""},{"id":281090157,"identity":"1b07cb82-80c5-4c81-9954-2f0f392c71a7","order_by":4,"name":"Dongsheng Fan","email":"","orcid":"","institution":"Luoyang Central Hospital Affiliated to Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Dongsheng","middleName":"","lastName":"Fan","suffix":""},{"id":281090158,"identity":"3eb035e1-8111-4f05-9347-f525dca8dd9b","order_by":5,"name":"Bing Li","email":"","orcid":"","institution":"Nanyang Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Bing","middleName":"","lastName":"Li","suffix":""},{"id":281090160,"identity":"7d65c856-c2d9-4449-8826-bb9db6fa6cfa","order_by":6,"name":"Ke Fu","email":"","orcid":"","institution":"The First Affiliated Hospital of Nanyang Medical College","correspondingAuthor":false,"prefix":"","firstName":"Ke","middleName":"","lastName":"Fu","suffix":""},{"id":281090162,"identity":"dc0addf0-a1a8-4fe4-bed0-07fb0b55ad9b","order_by":7,"name":"Haixin Fang","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Haixin","middleName":"","lastName":"Fang","suffix":""},{"id":281090164,"identity":"b4d68e81-881b-46b0-9843-47f2d7ade028","order_by":8,"name":"Min Zhang","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Min","middleName":"","lastName":"Zhang","suffix":""},{"id":281090165,"identity":"789dd1e3-2c23-4e0d-85d0-189fa8bf2a2d","order_by":9,"name":"Lin Li","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Lin","middleName":"","lastName":"Li","suffix":""},{"id":281090166,"identity":"94f3701b-a0ac-4351-b9bd-e4e08250a53e","order_by":10,"name":"Yu Zhao","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Zhao","suffix":""},{"id":281090167,"identity":"4b74fec4-24ba-411c-8fa0-5e22f6ec7e76","order_by":11,"name":"Xuemin Jin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2UlEQVRIie3RIQvCUBDA8RsPXjpYfUOZn0A4eSCszK+yISwtGA2Ck4HNvrAPIQirPhCWFOuiQzAtaDEZNGraswm+f/9xdxyAyfSD2b1ToK40c207VXrESYK6zialdLIy0COkwrPEKwvXKibNzdQu6iBxK1H7W9WA7/aTFmEtlpGTU5dZ6Wrj5TCWQ9VCGMNINMQ5g0PRQVBh0UY4t+8CiSGH+KJHEGE8eBGBEHM9IgSEdUYlCVFKLyeNW0YVvF75mM23x7SumqnvtpLPkaj7mjfyrTCZTKa/6AnHVEMdV/KfWgAAAABJRU5ErkJggg==","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":true,"prefix":"","firstName":"Xuemin","middleName":"","lastName":"Jin","suffix":""},{"id":281090168,"identity":"b55c5a5a-7312-45b8-a3ef-02009cd93b0b","order_by":12,"name":"Liping Du","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Liping","middleName":"","lastName":"Du","suffix":""}],"badges":[],"createdAt":"2024-03-02 02:34:58","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4005199/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4005199/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":53111742,"identity":"a68ad0cd-10f9-41e3-b593-65f31177ba1a","added_by":"auto","created_at":"2024-03-20 17:45:19","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2248489,"visible":true,"origin":"","legend":"\u003cp\u003eThe cSSO images (a type of IR image) (A2,3; B2,3; C2,3) and the SS-OCT B-scan images (A1; B1; C1) of AMN lesions. AMN lesions were dark or gray with well-demarcated margins with oval (B1), petal-shaped (C1), multifocal dark spots (D1). The acute phase of AMN lesions exhibited one or more abnormal characteristics, including outer retinal hyperreflectivity in SS-OCT B-scan images (B2, B3, B4). The shape of the lesion was consistent with the nerve fiber direction of the cone and rod cells (A2, A3, B4 yellow dotted line). The later period of AMN lesions exhibited ellipsoid zone loss (C2, C3) and thinning of the outer nuclear layer (D2, D3).\u003c/p\u003e","description":"","filename":"Fig.1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4005199/v1/5d2871bd84d143099869af2d.jpg"},{"id":53111737,"identity":"ee5fbe08-ba79-40d2-94f8-452a62363cdc","added_by":"auto","created_at":"2024-03-20 17:45:18","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2102738,"visible":true,"origin":"","legend":"\u003cp\u003eMultimodal fundus images of a 40-year-old female with AMN.Fundus photos (A), SS-OCT B-scan images (B), IR images (C), AO images (D), mf ERG (F) and micro-VF images (F). The BCVAs of her right and left eyes were 0.52 and 0.30 LogMAR (A; B1,2; F). After a month, the BCVAs of her right and left eyes increased to 0.1 and 0.00 LogMAR (B3,4; C; D; E). Compared with B1 and B2, the ellipsoid zone loss in B3 and B4 was largely restored, and the macular edema in B1 disappeared in B3.\u003c/p\u003e","description":"","filename":"Fig.2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4005199/v1/3ee366a53b92307c1307be5a.jpg"},{"id":53111740,"identity":"758a9bb3-370b-4bb5-9731-ff4ca2f1b1f2","added_by":"auto","created_at":"2024-03-20 17:45:19","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":846390,"visible":true,"origin":"","legend":"\u003cp\u003eMultimodal fundus images of an 11-year-old female with AMN. Micro VF and fundus photos (A), mf ERG (B), IR images (C) and \u003cem\u003een face\u003c/em\u003e images analyzed based on SS-OCTA and SS-OCT B-scan images (E). The BCVAs of her right and left eyes were 0.80 and 0.70 LogMAR. The area enclosed by the yellow line shows the extent of the lesion. The dark area on the \u003cem\u003een face\u003c/em\u003e image (E) was consistent with the range of ellipsoid loss in the B-scan (green dashed line), which was smaller than those areas on Micro VF, mf ERG and IR images.\u003c/p\u003e","description":"","filename":"OnlineFig.3.png","url":"https://assets-eu.researchsquare.com/files/rs-4005199/v1/a3e4ee8c2eab675ddddadade.png"},{"id":53111738,"identity":"5088f42f-7e2c-4b0b-9e12-2b1df2ca1422","added_by":"auto","created_at":"2024-03-20 17:45:19","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":2070593,"visible":true,"origin":"","legend":"\u003cp\u003eMultimodal fundus images from a 49-year-old male (A, B, C, D, E) and a 43-year-old male (F, G). The vitreous was opaque(A) at the beginning of the 49-year-old male. FFA (B) and ICGA (C) showed optic disc leakage and fluorescence accumulation in the advanced macula. After 3 days of treatment, the vitreous opacity was reduced (D), and neuroepithelial detachment decreased (E). Another 43-year-old male, her FFA (F) showed optic disc leakage at the beginning of the 43-year-old male. After treatment, neuroepithelial detachment decreased, and choroidal thickness was reduced with time (G).\u003c/p\u003e","description":"","filename":"Fig.4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4005199/v1/e72bb9eabf513055558c9a7e.jpg"},{"id":53111743,"identity":"dce7d21d-410a-47ae-97f7-5c85c00eb614","added_by":"auto","created_at":"2024-03-20 17:45:20","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":3578808,"visible":true,"origin":"","legend":"\u003cp\u003eMultimodal fundus images from a 21-year-old maleFundus photos (A), FAF (B), OCT (C), mf ERG (D), and FFA (E). The area enclosed by the yellow line and indicated by a yellow arrowhead in A2 shows the extent of the lesion. The range of ellipsoid loss in C2 was shown (yellow arrow).\u003c/p\u003e","description":"","filename":"Fig.5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4005199/v1/3462b45a868956c50192d762.jpg"},{"id":53112367,"identity":"93822775-99bc-4f80-88d3-85f57501c898","added_by":"auto","created_at":"2024-03-20 17:53:19","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":763403,"visible":true,"origin":"","legend":"\u003cp\u003eMultimodal fundus images from a 49-year-old male patient (A, B, C, D) and a 49-year-old female patient (E, F). White arrowhead showed the cherry erythema in B1, while yellow arrowhead showed the cotton-wool spots in B3 where the nerve fiber layer was swelling(C3). F1 showed the acute phase of arterial occlusion with extensive retinal edema.\u003c/p\u003e","description":"","filename":"Figure.6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4005199/v1/14d93188f30a3547f44fd824.jpg"},{"id":53112711,"identity":"16b3b853-ace0-4762-aad0-8ebe983a1bc4","added_by":"auto","created_at":"2024-03-20 18:01:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2872764,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4005199/v1/08dd9b93-b439-4a6e-9599-86358d6782d9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Rare Fundus Lesions in Patients after SARS-Cov-2 Infection: A Multicenter and Multimodal Imaging Study","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a potentially fatal disease with a serious life-threatening respiratory infection and multiorgan involvement\u003csup\u003e1\u003c/sup\u003e. SARS-Cov-2 primarily affects the anterior segment of the eye. The most frequently reported ocular conditions include conjunctival hyperemia, chemosis, epiphora, and even frank conjunctivitis\u003csup\u003e2, 3\u003c/sup\u003e. It is controversial whether SARS-Cov-2 affected the retina in the early stages of the COVID-19 pandemic\u003csup\u003e4\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSince 2019, the SARS-COV-2 virus has undergone adaptive mutation that could lead to an increase in transmissibility and virulence or a change in the presentation of clinical disease\u003csup\u003e5\u003c/sup\u003e. The Delta variant was identified in December 2020, and the Omicron variant was identified in November 2021, both of which caused surges in the number of infections\u003csup\u003e6\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eWith the increasing number of COVID-19 patients, a growing number of changes have been observed in the retina and choroid\u003csup\u003e7\u003c/sup\u003e. In 2020, a cross-sectional study revealed retinal lesions associated with SARS-Cov-2, including dilated veins (27.7%), tortuous vessels (12.9%), retinal hemorrhages (9.25%), and cotton-wool spots (7.4%)\u003csup\u003e8\u003c/sup\u003e. A review in 2022 suggested the potential involvement of the posterior segment in SARS-Cov-2, either in the initial or later stage\u003csup\u003e9\u003c/sup\u003e. However, few studies have systematically described the manifestations of the posterior segment of the eye by multimodal imaging study\u003csup\u003e10\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDue to the lockdown policy was suddenly lifted, there was a surge in the number of Omicron infections in Chinese people from late December 2022 to late January 2023 in China\u003csup\u003e11\u003c/sup\u003e. Based on the large number of SARS-Cov-2 infected patients, it was possible for us to observe a series of patients with rare fundus Lesions after SARS-Cov-2 infection. These rare fundus lesions with a large increase over the same period of the previous year may be related to SARS-Cov-2 infection. Because these lesions are rare and often lead to misdiagnosis, reasonable examination methods can help us quickly identify lesions and diagnose them.\u003c/p\u003e \u003cp\u003eIn the present case series, multimodality imaging was used to describe retinal and/or choroidal conditions that could be associated with SARS-Cov-2 infections. We outlined the features of retinal and choroidal manifestations following SARS-Cov-2 infections and clarified the best diagnostic methods to improve our understanding of their pathogenesis and diagnosis.\u003c/p\u003e"},{"header":"2 Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Participants\u003c/h2\u003e \u003cp\u003eThis was a cross-sectional multicenter and multimodal imaging study. From December 2022 to February 2023, 90 patients were identified with retinal and/or choroidal conditions associated with COVID‑19 infection in six clinics, including the First Affiliated Hospital of Zhengzhou University and/or Zhengzhou University People\u0026rsquo;s Hospital and/or The Second People's Hospital of Zhengzhou and/or Luoyang Central Hospital Affiliated to Zhengzhou University and/or Nanyang Eye Hospital, Nanyang and/or The First Affiliated Hospital of Nanyang Medical College. The incidence of these diseases in the same period of the previous year was collected from the outpatient information databases of those hospitals\u003c/p\u003e \u003cp\u003eAll patients tested positive by real‑time reverse transcription‑polymerase chain reaction (RT‑PCR) and/or antigen detection for SARS‑CoV‑2 from pharyngeal or nasopharyngeal swabs during the active phase of SARS‑CoV‑2 infection and eye symptoms occurred whitin one month after SARS‑CoV‑2 infection. Patients who were not infected with SARS‑CoV‑2 and whose ocular symptoms occurred more than one month after SARS‑CoV‑2 infection were excluded.\u003c/p\u003e \u003cp\u003e This study was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University [2023-KY-0637]. Based on the \u003cem\u003eDeclaration of Helsinki\u003c/em\u003e, we collected demographic information, SARS‑CoV‑2 infection symptoms, chief complaints and other clinical examination results after informed consent was signed by the patients or their guardians. The clinical examination results included slit‑lamp examination and indirect ophthalmoscopy results, best corrected visual acuity (BCVA), spherical equivalent (SE), fundus photo images, visual field analysis (VF), infrared retinal photographs (IR), optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), multifocal electrophysiology (mf ERG), fundus autofluorescence (FAF) and adaptive optics (AO). All patients were diagnosed and recorded by 2 doctors individually. In cases of disagreement, the senior ophthalmologist made the final decision.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Method of Eye Examination\u003c/h2\u003e \u003cp\u003eAll outpatients were examined by slit‑lamp and ophthalmoscopy. BCVA and SE were tested by optometrists. Fundus photos and FAF were taken using an ultrawide field fundus camera (Daytona P200T, Optomap, UK) and fundus camera (CLARUS 500 v1.1, Carl Zeiss Co. Ltd., Germany).\u003c/p\u003e \u003cp\u003emf ERG (RETI-scan multifocal ERG (Roland Consult, Germany) was performed on the patients. VF examination (Humphrey Field Analyzer 3, Carl Zeiss Co. Ltd., Germany) or micro examination (MP3-microperimerter Ver.1.2.1, NIDEK Co. Ltd., Japan) was selected according to the patient's symptoms.\u003c/p\u003e \u003cp\u003eSkilled ophthalmologists performed swept source OCT (SS-OCT) (VG200 or VG100, SVision, China) or spectral domain OCT (SD-OCT) (Spectralis OCT, Heidelberg Engineering GmbH, Germany), which included stars in 16 or 32 lines and multiline scanning with a scan line length of 10 to 16 mm. SS-OCTA scanning was performed with a scan square of 6 mm\u0026times;6 mm or 12 mm\u0026times;12 mm. The depth of the scanning was 3 to 6 mm. The scanning laser wavelength was 1050 nm or 870 nm. IR images were taken by a 40\u0026deg;\u0026times;40\u0026deg; confocal scanning superluminescent (diode) ophthalmoscope (cSSO) with a wavelength of 820 nm or confocal scanning laser ophthalmoscope (cSLO) with a wavelength of 810 nm.\u003c/p\u003e \u003cp\u003eFFA and ICGA (Spectralis HRA, Heidelberg Engineering GmbH, Germany) were performed to observe vascular lesions. AO (rtx1, Imagine Eyes, Orsay, France) was performed to clarify the status of the optic cone optic rod cells.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Statistical Analysis\u003c/h2\u003e \u003cp\u003eSPSS statistics 26.0 software (IBM Corp.; USA) were used to analyze the data. Categorical data are described using frequencies and percentages. The Kolmogorov‒Smirnov test was performed to verify whether all the data sets were distributed normally. Continuous variables with a normal distribution are presented as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD), and a \u003cem\u003et\u003c/em\u003e test was used for comparisons. Nonnormal variables are reported as medians (interquartile ranges). A \u003cem\u003eP\u003c/em\u003e value less than or equal to 0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e3.1 COVID-19 infection, vaccination history and demographics of patients\u003c/h2\u003e \u003cp\u003eNinety patients were included in this study, including 24 males (26.67%) and 66 (73.33%) females. Their age was 31\u0026thinsp;\u0026plusmn;\u0026thinsp;15 years old with a range of 10 to 85 years (Table\u0026nbsp;1).\u003c/p\u003e \u003cp\u003eAll patients had a history of COVID-19 infection. Visual symptoms occurred 0 days to 30 days after the onset of fever, dry cough, malaise, etc. The mean interval between COVID-19 infection and visual symptom onset was 2 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) days. Five patients had diabetes, six patients had kidney disease, four patients had hypertension.\u003c/p\u003e \u003cp\u003eTabel.1 COVID-19 history and demographics of patients\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisease\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber\u003c/p\u003e \u003cp\u003eof cases (male cases)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;90 (34, 37.78%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eVisual symptoms occurred after COVID-19 symptoms\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCombined with\u003c/p\u003e \u003cp\u003ePurtscher-like retinopathy\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute macular neuroretinopathy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e78 (22, 28.21%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29\u0026thinsp;\u0026plusmn;\u0026thinsp;11 yrs.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 to 20 days\u003c/p\u003e \u003cp\u003eAverage 2(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple evanescent white-dot syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2(1, 50.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 and 37 yrs. respectively\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVogt-Koyanagi-Harada syndrome-like uveitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3(0, 0.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34,43 and 49 yrs. respectively\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,5 and 7 days respectively\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRhino-orbital-cerebral mucormycosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5(1, 20.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 to 30 days\u003c/p\u003e \u003cp\u003eAverage 14\u0026thinsp;\u0026plusmn;\u0026thinsp;10 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWe reviewed the detailed COVID-19 infection history, medication history and vaccination history in 33 of the 90 patients. All patients had a fever of 37.5 to 40℃. Among them, 24 patients (71.88%) took ibuprofen, acetaminophen or Tylenol to reduce fever, whereas 9 (28.125%) did not. Twelve patients (36.37%) were dehydrated (sweating profusely and unable to drink) prior to the onset of symptoms, while 20 patients (63.63%) were dehydrated. Seven patients (21.21%) received 2 doses of inactivated COVID-19 vaccine, 19 patients (57.58%) received 3 doses of inactivated COVID-19 vaccine, and 7 patients (21.21%) did not receive inactivated COVID-19 vaccine.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Clinical Characteristics of Our Case Series and Multimodal Imaging\u003c/h2\u003e \u003cp\u003eAmong all patients, 78 (86.66%) were diagnosed with acute macular neuroretinopathy (AMN). The remaining 12 patients were diagnosed with simple Purtscher-like retinopathy (2 patients, 2.22%), Vogt‒Koyanagi‒Harada-like (VKH-like) uveitis (3 patients, 3.33%), multiple evanescent white-dot syndrome (MEWDS) (2 patients, 2.22%), and rhino-orbital-cerebral mucormycosis (ROCM) (5 patients, 5.56%).\u003c/p\u003e \u003cp\u003eHowever, in December 2021 to February 2022 year, there were only one Purtscher retinopathy patient with chest trauma, one ROCM patient and two AMN patients. Although there are as many as 21 patients first diagnosed as VKH, their clinical symptoms are different from those after SARS-Cov-2 infection. The number of MEWDS patient cannot obtain because MEWDS does not have an ICD diagnostic code.\u003c/p\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003e3.2.1 Acute Macular Neuroretinopathy (AMN) and Purtscher or Purtscher-like Retinopathy\u003c/h2\u003e \u003cp\u003eA total of 78 patients (146 eyes) were diagnosed with AMN, including 22 males (28.21%) and 56 (71.79%) females. Their age was 29\u0026thinsp;\u0026plusmn;\u0026thinsp;11 years old with a range of 10 to 64 years old. The majority of patients were young women (67.95%). There was no statistically significant difference in age between the sexes (\u003cem\u003et\u003c/em\u003e = -0.22, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.830). Their complaints were \"black shadows or dark spots in front of the eyes or visual field defects\" (38 cases, 48.72%) and \"blurred vision. \"(40 cases, 51.28%).\u003c/p\u003e \u003cp\u003eTen patients (12.82%) had visual problems in one eye. Sixty-eight patients (87.18%) had visual problems in both eyes. The BCVA of the 146 diseased eyes was 0.13 (0.00, 0.63) logMAR with a range of 0.00 to 2.00 Log MAR. In a total of 146 eyes with AMN, the BCVAs at presentation were generally well documented to be 0.30 LogMAR or better (96 eyes, 65.75%). 1.00 LogMAR or worse in 18 eyes (12.33%).\u003c/p\u003e \u003cp\u003eNineteen cases (38 eyes) of 78 cases (146 eyes) (24.36%, 26.03%) combined cotton-wool spots or Purtscher-like retinopathy at the initial visit (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). Ten of these patients (52.63%) had kidney disease or hypertension.\u003c/p\u003e \u003cp\u003eOCT with IR were used in 146 eyes (100.00%), and in each IR image, AMN lesions were dark or gray with well-demarcated margins with oval (Fig.\u0026nbsp;1B1), petal-shaped (Fig.\u0026nbsp;1C1), multifocal dark spots (Fig.\u0026nbsp;1D1). AMN lesions on OCT exhibited one or more abnormal characteristics, including outer retinal hyperreflectivity (Fig.\u0026nbsp;1B3 4 yellow arrowhead), ellipsoid zone loss (Fig.\u0026nbsp;1C3 yellow arrows), small cavity in macular (Fig.\u0026nbsp;2B1 yellow arrowhead) and thinning of the outer nuclear layer (ONL) (Fig.\u0026nbsp;1D3 yellow arrowhead).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFundus photos were taken in 57 of 146 eyes. The lesions showed wedge-shaped petal-shaped, oval slightly dark areas in 16 eyes (28.07%) (Fig.\u0026nbsp;3A1, A2 white arrowheads). The contrast sensitivity of the fundus photo was not as good as that of IR and OCT. Ten eyes underwent mf ERG and all showed one to several abnormal findings, including diminished amplitudes and diminished implicit time (Fig.\u0026nbsp;3A1, A2 white arrowheads). Thirty-six eyes with AMN experienced one to several paracentral scotomas by Amsler grid, VF or micro-VF testing. The mf ERG and VF specialty corresponded closely to the shape and location of the clinical lesion (Fig.\u0026nbsp;3F1, F2). The shape of VF abnormalities was wedge-shaped, boot-shaped, and round-shaped. Four eyes underwent AO and showed small patches of cone rod cell loss in the area corresponding to the lesions (Fig.\u0026nbsp;2D1, D2 yellow boxes).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003e3.2.2 VKH-like uveitis and Multiple Evanescent White-Dot Syndrome (MEWDS)\u003c/h2\u003e \u003cp\u003eA 49-year-old female patient complained of \"visual distortion in both eyes accompanied by tinnitus.\" Her right and left BCVAs were 0.52 and 1.3 Log MAR, respectively. After fever, she was diagnosed with SARS-Cov-2 infection via an antigen test. She went to the hospital after developing hazy vision in her left eye five days later. After a month, her right eye also appeared blurry, so she sought medical attention. Both eyes had congested conjunctiva and adherent irises; the vitreous was cloudy, and the fundus was not visible. (Fig.\u0026nbsp;4A1, A2). We administered prednisone (60 mg once a day), tobramycin dexamethasone eye drops (1 drop every 4 hours), and 0.1% atropine eye ointment (1 drops twice a day). Three days later, symptoms of the anterior segment were reduced, and the fundus was visible (Fig.\u0026nbsp;4D1, D2). OCT showed neuroepithelial detachment (Fig.\u0026nbsp;4E1, E2). After 10 days, the BCVA of her right and left eyes improved to 0.22 and 0.30 LogMAR, respectively, and the neuroepithelial detachment diminished.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAnother 43-year-old female complained of \"blurred vision on both eyes without headache and tinnitus.\" The BCVAs in both eyes were 0.10 LogMAR 4 days after fever caused by SARS-Cov-2. We applied FFA and OCT to her eyes (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eF, G). We diagnosed her with VKH-like uveitis and administered prednisone (60 mg once a day) and 0.1% atropine eye ointment (1 drop twice a day). She felt better, and the BCVAs improved to 0.00 LogMAR in both eyes seven days later. FFA and OCT showed that neuroepithelial detachment was reduced and eliminated with time (Fig.\u0026nbsp;4G1, G2). She only received one month of hormone treatment and did not relapse for half a year.\u003c/p\u003e \u003cp\u003eThese two patients didn\u0026rsquo;t have headache or tinnitus or skin/hair change. They were highly sensitive to glucocorticoids, had good visual prognoses, and didn\u0026rsquo;t relapse in a short time after discontinuation of glucocorticoids. These were different from the classic VKH syndrome, so we named it VKH-like uveitis.\u003c/p\u003e \u003cp\u003eA 21-year-old male patient was diagnosed with MEWDS and complained of \"blurred vision on the left eye\" five days after a fever caused by SARS-Cov-2. The BCVAs were 0.00 and 0.10 LogMAR in his right and left eyes. Some yellow-white punctate lesions were faintly seen on fundus photography (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA2), OCT showed that there were structural abnormalities in the outer retina (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eC2). The mf ERG showed that the visual sensitivity of the patient's left eye was reduced (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eD2). There were some highly fluorescent lesions on the FAF (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eB2). F) and scattered high fluorescence spots on FFA (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. B2). However, the patient did not undergo ICGA due to drug allergies. We suggested that the patient should return to the clinic two weeks later, but he did not return. Then, we performed a telephone follow-up and were informed that his symptoms had been eliminated. Another 37-year-old female had similar symptoms.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section3\"\u003e \u003ch2\u003e3.2.3 Rhino-orbital-cerebral Mucormycosis (ROCM)\u003c/h2\u003e \u003cp\u003eA 49-year-old male patient with SARS-Cov-2-related pneumonia had recurrent fever for 20 days and underwent \"intracranial hematoma drainage\" because of \"diabetic ketoacidosis and cerebral hemorrhage.\" Then, he developed swelling on the right side of the face 3 days later. Sooner afterward, he suddenly lost vision in his right eye. This patient had a history of high blood pressure and diabetes but did not take medications regularly. Due to fever and infection, his vital signs were unstable, and his right eye was not treated (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eB). B1). Pale retinal and \u0026ldquo;cherry erythema\u0026rdquo; suggested central retinal artery occlusion (CRAO). Fungal cultures of nasal tissue in patients showed wide septum hyphae, which was characteristic of Mucormyces. This confirmed that he had ROCM. The patient's right eyeball was fixed in the upper right position and could only be slightly moved up and down instead of left and right (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eB). A). Unfortunately, the optic disc of the right eye was pale (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eB). Interestingly, we observed cotton-wool spots around the optic disc of the left eye (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eB2). B3). OCT showed retinal-choroidal atrophy and interlaminar edema in his right eye (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eB). C1). The cotton-wool patch showed thickening of the neuroepithelium (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eB). C3). The patient's magnetic resonance imaging (MRI) showed abnormal signals in the right orbital tip (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eB). D).\u003c/p\u003e \u003cp\u003eAnother 49-year-old female patient was also diagnosed with ROCM. She also had diabetic ketoacidosis, which suggested poor glycemic control. Similarly, she lost her vision in her right eye. Fundus photographs showed cotton-wool spots and bleeding on her left eye as well (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eE). Blood tests showed that her white blood cells were 13.68 (reference 3.5\u0026ndash;9.5) 10^9/L, neutrophil percentage was 83.5% (reference 40\u0026ndash;75%), DD-dimer was as high as 10.79 (reference 0-0.3) mg/L (DDU), fibrinogen degradation products (FDP) were as high as 10.79 (reference 0\u0026ndash;5) mg/L, and C-reactive protein (CRP) and procalcitonin (PCT) and interleukin 6 (IL-6) were more than 5 times the normal value.\u003c/p\u003e \u003cp\u003eBoth patients were not treated because their vision was no light projection (NLP). In addition, three other female patients aged 77, 81, and 85 years who had ROCM and diabetes underwent eye removal.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eSince the COVID-19 pandemic in November 2019, over 757\u0026nbsp;million confirmed cases and over 6.8\u0026nbsp;million deaths have been reported around the world\u003csup\u003e12\u003c/sup\u003e. SARS-CoV-2 infects host cells through the transmembrane spike protein (S protein), which in turn infects human endothelial cells with ACE2 as its receptor, so tissues with ACE2 receptors are susceptible to SARS-CoV-2 infection\u003csup\u003e13\u003c/sup\u003e. ACE2 is widely expressed in endothelial cells of the lung, blood vessels, heart, kidney, small intestine and other tissues and organs, with a small amount of expression in the liver and nose. The above organs are vulnerable to damage after infection with SARS-CoV-2\u003csup\u003e14, 15\u003c/sup\u003e. Moreover, ACE2 is a major converting enzyme in the vascular protective axis of the renin-angiotensin system in the retina, and its downregulation may lead to retinal ischemia, which is related to microangiopathy, retinitis, and retinal degeneration\u003csup\u003e15\u0026ndash;17\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePrevious literature has reported retinal and choroidal manifestations that may be associated with SARS-CoV-2 as shown in Table\u0026nbsp;2. Depending on the pathological mechanism, we classify it as noninfectious or infectious. Noninfectious manifestations may be related to ischemia or inflammation. RVO and RAO are common diseases in ophthalmology, and patients often have underlying diseases such as diabetes and hypertension\u003csup\u003e18, 19\u003c/sup\u003e. Therefore, these diseases were not included in our case series as fundus lesions related to SARS-CoV-2. However, uncommon eye diseases such as AMN and ROCM have increased in incidence alongside the rise in SARS-CoV-2 infection rates\u003csup\u003e20, 21\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTabel.2 Retinal and choroidal manifestations in patients after SARS-CoV-2 infection\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabb\" border=\"1\"\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eType of the manifestations\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eClinical findings / Disease\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo-infectious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRetinal vein occlusion (RVO)\u003csup\u003e14, 15\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eRetinal artery occlusion (RAO)\u003csup\u003e16\u003c/sup\u003e\u003c/p\u003e \u003cp\u003ePurtscher-like retinopathy\u003csup\u003e17\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eCotton-wool spots\u003csup\u003e18\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIsolated hemorrhages\u003csup\u003e19\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c3\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAcute macular neuroretinopathy (AMN)\u003csup\u003e20\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eParacentral acute middle maculopathy (PAMM)\u003csup\u003e21\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAcute posterior multifocal placoid pigment epitheliopathy (APMPPE)\u003csup\u003e22\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eMultiple evanescent white-dot syndrome (MEWDS)\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eSerpiginous choroiditis (SC)\u003csup\u003e23\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOptic neuritis (ON)\u003csup\u003e24\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eVogt-Koyanagi-Harada syndrome-like uveitis\u003csup\u003e25\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eCentral serous chorioretinopathy (CSCR)\u003csup\u003e26\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c3\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfectious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEndogenous endophthalmitis (Bacterial / Fungal)\u003csup\u003e27\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAcute retinal necrosis (ARN)\u003csup\u003e28\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eRhino-orbital-cerebral mucormycosis (ROCM)\u003csup\u003e29\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c3\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003e4. 1 Acute macular neuroretinopathy (AMN) and Purtscher or Purtscher-like retinopathy\u003c/h3\u003e\n\u003cp\u003eWe observed this case series with SARS-CoV-2-related retinal and choroidal manifestations. Typically, the patient was a young woman who developed visual impairment two days following the onset of infection symptoms. As the standard, with the relationship of cause, trigger and disease, our results suggested a close relationship between the emergence of AMN or Purtscher or Purtscher-like retinopathy and SARS-CoV-2 infection.\u003c/p\u003e \u003cp\u003eAMN is a relatively rare disorder involving transient or permanent central or paracentral scotomas\u003csup\u003e39\u003c/sup\u003e. It is characterized by dark, reddish-brown macular lesions and corresponds precisely to visual field abnormalities\u003csup\u003e40\u003c/sup\u003e. AMN has been reported to occur in several different clinical settings. The majority of patients are women in their reproductive years who develop symptoms in association with oral contraceptives, hypotension, viral illness, intravitreous injection, vaccination and sympathomimetic agents (epinephrine, caffeine).\u003csup\u003e3, 41\u0026ndash;47\u003c/sup\u003e. Since the syndrome was initially characterized by Bos and Deutmann\u003csup\u003e48\u003c/sup\u003e in 1975, the pathophysiology of AMN has been the subject of intense discussion, especially in light of the disorder's diverse causes.\u003c/p\u003e \u003cp\u003eAcute retinal lesions are characterized by faint retinal translucency on bio microscopy and hyperreflectivity in the outer plexiform and outer nuclear layers on OCT. FFA and ICGA do not reveal any retinal or choroidal vascular leakage, perfusion deficits or transmission defects. mfERG testing shows reduced amplitudes within the scotomatous areas\u003csup\u003e49\u003c/sup\u003e. Evolution of macular lesions is characterized by resolution within several days of the initial retinal translucency and hyperreflectivity, followed by the development of reddish-brown lesions that appear dark on IR and show thinning of the outer nuclear layer and attenuation or loss of the ellipsoid and interdigitation zones on OCT. Compared to FFA, ICGA and FAF, OCT and IR images display the lesions of AMN more effectively. The cSSO fundus photography used in this study is a laser with a wavelength of 820 nm; it is also an IR imaging approach in essence. Due to the destruction of the elliptical zone, the laser is absorbed by the deeper and stronger retinal epithelium, demonstrating the essence of shadow and OCT is optical coherence imaging, and the areas with mixed or dense tissue structure will show high reflection\u003csup\u003e50\u003c/sup\u003e. From the perspective of imaging alone, the morphology of hyper reflex in the early stage of the onset of AMN was consistent with that of the fiber of the cone and rod cells, which indicates the affected site (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA)\u003csup\u003e40, 47\u003c/sup\u003e. At present, the generation of AMN is mainly dominated by two theories: the inflammation-related immune theory and the vascular-related ischemia and hypoxia theory\u003csup\u003e49, 51\u003c/sup\u003e. This needs to be discussed in combination with vascular parameters, and our research team will explore in future research.\u003c/p\u003e\n\u003ch3\u003e4. 2 VKH-like uveitis and Multiple Evanescent White-Dot Syndrome (MEWDS)\u003c/h3\u003e\n\u003cp\u003eVKH disease is an immune-mediated disorder characterized by bilateral uveitis frequently associated with neurological (meningeal), auditory, and integumentary symptoms. Auditory manifestations (tinnitus, hearing loss and vertigo) and others (including headache, neck and back stiffness) usually occur before or concurrently with ocular involvement\u003csup\u003e52\u003c/sup\u003e. A previous study linked VKH to SARS-CoV-2 Vaccines \u003csup\u003e53\u003c/sup\u003e. The VKH-like patients in this series responded favorably to corticosteroid therapy. Whether SARS-CoV-2 is a precipitating factor or a disease inducer will require longer-term observation. MWDES is related to colds and viral infections. Both patients in this study developed symptoms five days after experiencing SARS-CoV-2-related fever, which is considered a cause.\u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e4.3 Rhino-orbital-cerebral Mucormycosis (ROCM)\u003c/h2\u003e \u003cp\u003eROCM can be a serious complication of severe SARS-CoV-2 infection, particularly in patients with uncontrolled diabetes. The risk factors predisposing patients to ROCM are uncontrolled diabetes, neutropenia, hematological malignancies, organ transplantation, trauma and burn, and use of immunosuppressants such as corticosteroids\u003csup\u003e37, 38\u003c/sup\u003e. Patients were often blinded by mucormycosis invasion of the orbital apex leading to orbital apex syndrome forming retinal artery obstruction. This disease is easily misdiagnosed due to its reputation as a difficult-to-treat mold infection and its high mortality in patients with SARS-CoV-2 infection, particularly those with pulmonary disease. A careful management plan can be successful for rhino-orbital cerebral disease if there is early diagnosis of infection and control of infection\u003csup\u003e54\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn conclusion, the retinal and choroidal conditions after SARS-CoV-2 infection are diverse, including AMN, MEWDS, VKH-like uveitis, and ROCM. Multimodal imaging may be used to evaluate the lesions from the anatomical and functional levels, and an appropriate examination with multimodal imaging is beneficial for patient management and follow-up.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by National Natural Science Foundation of China [819707922 and \u0026nbsp;82171040] and Medical Science and Technology Project of Health Commission of Henan Province [YXKC2020026].\u003c/p\u003e\n\u003cp\u003eThe authors would like to\u0026nbsp;thank Dr. Kang Chen for providing us free mf ERG test and thank Dr. Yubao Zheng in Nanyang Eye Hospital, Dr. Ming Hou in Luoyang Central Hospital Affiliated to Zhengzhou University, Dr. Jing Wng, Dr. Zhenzhen Liu in The First Affiliated Hospital of Zhengzhou University and Dr. Shiqing Li, Dr. Qingge Guo, Dr. Xiao Chen, Dr. Xiaohong Guo, Dr. Changgeng Liu in Henan Eye Hospital for providing us fundus photos, OCT and FFA images\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConception and design: An, Du, Jin\u003c/p\u003e\n\u003cp\u003eData collection: An, Wang, Yang, Fan, Li, Fu, Fang, Zhang, Zhao, Chen\u003c/p\u003e\n\u003cp\u003eAnalysis and interpretation: An\u003c/p\u003e\n\u003cp\u003eObtained funding: Lei, Du, Jin\u003c/p\u003e\n\u003cp\u003eOverall responsibility: An, Wang, Li, Lei, Du, Jin\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosures:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere are no financial conflicts of interest to disclose.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSharma A, Tiwari S, Deb MK, Marty JL. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): a global pandemic and treatment strategies. Int J Antimicrob Agents. Aug 2020;56(2):106054. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ijantimicag.2020.106054\u003c/span\u003e\u003cspan address=\"10.1016/j.ijantimicag.2020.106054\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCosta IF, Bonifacio LP, Bellissimo-Rodrigues F, et al. Ocular findings among patients surviving COVID-19. Sci Rep. May 26 2021;11(1):11085. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41598-021-90482-2\u003c/span\u003e\u003cspan address=\"10.1038/s41598-021-90482-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSen M, Honavar SG, Sharma N, et al.COVID-19 and Eye: A Review of Ophthalmic Manifestations of COVID-19. Indian J Ophthalmol. Mar 2021;69(3):488\u0026ndash;509. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4103/ijo.IJO_297_21\u003c/span\u003e\u003cspan address=\"10.4103/ijo.IJO_297_21\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKarampelas M, Dalamaga M, Karampela I. Does COVID-19 Involve the Retina? Ophthalmol Ther. Sep 21 2020:1\u0026ndash;3. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s40123-020-00299-x\u003c/span\u003e\u003cspan address=\"10.1007/s40123-020-00299-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHarvey WT, Carabelli AM, Jackson B, et al. SARS-CoV-2 variants, spike mutations and immune escape. Nat Rev Microbiol. Jul 2021;19(7):409\u0026ndash;424. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41579-021-00573-0\u003c/span\u003e\u003cspan address=\"10.1038/s41579-021-00573-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAleem A, Akbar Samad AB, Slenker AK. Emerging Variants of SARS-CoV-2 And Novel Therapeutics Against Coronavirus (COVID-19). StatPearls. 2022.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJevnikar K, Jaki Mekjavic P, Vidovic, et al.An Update on COVID-19 Related Ophthalmic Manifestations. Ocul Immunol Inflamm. May 19 2021;29(4):684\u0026ndash;689. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/09273948.2021.1896008\u003c/span\u003e\u003cspan address=\"10.1080/09273948.2021.1896008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eInvernizzi A, Torre A, Parrulli S, et al. Retinal findings in patients with COVID-19: Results from the SERPICO-19 study. EClinicalMedicine. Oct 2020;27:100550. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.eclinm.2020.100550\u003c/span\u003e\u003cspan address=\"10.1016/j.eclinm.2020.100550\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang Y, Stewart JM. Retinal and choroidal manifestations of COVID-19. Curr Opin Ophthalmol. Nov 1 2021;32(6):536\u0026ndash;540. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/ICU.0000000000000801\u003c/span\u003e\u003cspan address=\"10.1097/ICU.0000000000000801\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcGrath OE, Aslam TM. Use of Imaging Technology to Assess the Effect of COVID-19 on Retinal Tissues: A Systematic Review. Ophthalmol Ther. Jun 2022;11(3):1017\u0026ndash;1030. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s40123-022-00509-8\u003c/span\u003e\u003cspan address=\"10.1007/s40123-022-00509-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePan Y, Wang L, Feng Z, et al. Characterisation of SARS-CoV-2 variants in Beijing during 2022: an epidemiological and phylogenetic analysis. Lancet. Feb 25 2023;401(10377):664\u0026ndash;672. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0140-6736(23)00129-0\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(23)00129-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ehttps://\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e\u003c/span\u003e\u003cspan address=\"http://www.who.int/europe/emergencies/situations/covid-19\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Updated 2023.02.05.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJackson CB, Farzan M, Chen B, et al.Mechanisms of SARS-CoV-2 entry into cells. Nat Rev Mol Cell Biol. Jan 2022;23(1):3\u0026ndash;20. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41580-021-00418-x\u003c/span\u003e\u003cspan address=\"10.1038/s41580-021-00418-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuney C, Akar F. Epithelial and Endothelial Expressions of ACE2: SARS-CoV-2 Entry Routes. J Pharm Pharm Sci. 2021;24:84\u0026ndash;93. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.18433/jpps31455\u003c/span\u003e\u003cspan address=\"10.18433/jpps31455\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePagliaro P, Thairi C, Alloatti G, et al. Angiotensin-converting enzyme 2: a key enzyme in key organs. J Cardiovasc Med (Hagerstown). Jan 1 2022;23(1):1\u0026ndash;11. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2459/JCM.0000000000001218\u003c/span\u003e\u003cspan address=\"10.2459/JCM.0000000000001218\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYener AU. COVID-19 and the Eye: Ocular Manifestations, Treatment and Protection Measures. Ocul Immunol Inflamm. Aug 18 2021;29(6):1225\u0026ndash;1233. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/09273948.2021.1977829\u003c/span\u003e\u003cspan address=\"10.1080/09273948.2021.1977829\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLumbers ER, Head R, Smith GR, et al. The interacting physiology of COVID-19 and the renin-angiotensin-aldosterone system: Key agents for treatment. Pharmacol Res Perspect. Feb 2022;10(1):e00917. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/prp2.917\u003c/span\u003e\u003cspan address=\"10.1002/prp2.917\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHayreh SS, Podhajsky PA, Zimmerman MB. Retinal artery occlusion: associated systemic and ophthalmic abnormalities. Ophthalmology. Oct 2009;116(10):1928\u0026ndash;36. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ophtha.2009.03.006\u003c/span\u003e\u003cspan address=\"10.1016/j.ophtha.2009.03.006\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eModjtahedi BS, Do D, Shaw J. Correspondence Regarding Changes in the Incidence of Retinal Vascular Occlusions After COVID-19 Diagnosis-Reply. JAMA Ophthalmol. Nov 1 2022;140(11):1143\u0026ndash;1144. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamaophthalmol.2022.3479\u003c/span\u003e\u003cspan address=\"10.1001/jamaophthalmol.2022.3479\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAzar G, Bonnin S, Vasseur V, et al. Did the COVID-19 Pandemic Increase the Incidence of Acute Macular Neuroretinopathy? J Clin Med. Oct 28 2021;10(21)doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/jcm10215038\u003c/span\u003e\u003cspan address=\"10.3390/jcm10215038\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNehara HR, Kumawat S, Gupta J, et al. Coronavirus Disease, Diabetes and Glucocorticoid a Terrible Trio for Invasive Mucormycosis: An Observational Study from Northwest Rajasthan. J Assoc Physicians India. Dec 2022;69(12):11\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNourinia R, Ghassempour M, Ahmadieh H, Abtahi SH. Branch retinal vein occlusion after COVID-19. J Fr Ophtalmol. Oct 2021;44(8):e441-e443. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jfo.2021.06.003\u003c/span\u003e\u003cspan address=\"10.1016/j.jfo.2021.06.003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCuadros Sanchez C, Eguen CS, Gutierrez-Ezquerro R, et al. Central Retinal Vein Occlusion Presumably Associated with Lupus Anticoagulant Induced by SARSCoV-2. Ocul Immunol Inflamm. Oct-Nov 2022;30(7\u0026ndash;8):2010\u0026ndash;2013. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/09273948.2021.1933077\u003c/span\u003e\u003cspan address=\"10.1080/09273948.2021.1933077\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAu SCL, Ko CKL. Central Retinal Artery Occlusion in Patients with COVID-19: Imaging for Underlying Causes. Radiology. Jul 2021;300(1):E315. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1148/radiol.2021210479\u003c/span\u003e\u003cspan address=\"10.1148/radiol.2021210479\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThatcher MD, Wu LZ, Varma R. Bilateral Purtscher-Like Retinopathy Associated With COVID-19 Infection. JAMA Ophthalmol. Feb 9 2023;doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamaophthalmol.2022.6255\u003c/span\u003e\u003cspan address=\"10.1001/jamaophthalmol.2022.6255\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChan AX, Ritter M, Bakhoum MF. Bilateral cotton wool spots after ambulatory COVID-19. Int J Infect Dis. Apr 2021;105:414\u0026ndash;415. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ijid.2021.02.119\u003c/span\u003e\u003cspan address=\"10.1016/j.ijid.2021.02.119\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePereira LA, Soares LCM, Nascimento PA, et al. Retinal findings in hospitalised patients with severe COVID-19. Br J Ophthalmol. Jan 2022;106(1):102\u0026ndash;105. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bjophthalmol-2020-317576\u003c/span\u003e\u003cspan address=\"10.1136/bjophthalmol-2020-317576\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGiacuzzo C, Eandi CM, Kawasaki A. Bilateral acute macular neuroretinopathy following COVID-19 infection. Acta Ophthalmol. Mar 2022;100(2):e611-e612. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/aos.14913\u003c/span\u003e\u003cspan address=\"10.1111/aos.14913\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCastro CS, Ferreira AS, Silva NP, et al.Paracentral Acute Middle Maculopathy After COVID-19 Disease: Multimodal Evaluation. Retin Cases Brief Rep. Jul 15 2022;doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/ICB.0000000000001301\u003c/span\u003e\u003cspan address=\"10.1097/ICB.0000000000001301\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFischer NA, Wann RC, Crosson JN. Acute posterior multifocal placoid pigment epitheliopathy following COVID-19 infection. Am J Ophthalmol Case Rep. Mar 2023;29:101790. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ajoc.2022.101790\u003c/span\u003e\u003cspan address=\"10.1016/j.ajoc.2022.101790\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eProvidencia J, Fonseca C, Henriques F, et al.Serpiginous choroiditis presenting after SARS-CoV-2 infection: A new immunological trigger? Eur J Ophthalmol. Jan 2022;32(1):NP97-NP101. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/1120672120977817\u003c/span\u003e\u003cspan address=\"10.1177/1120672120977817\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLandecho MF, Yuste JR, Gandara E, et al. COVID-19 retinal microangiopathy as an in vivo biomarker of systemic vascular disease? J Intern Med. Jan 2021;289(1):116\u0026ndash;120. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/joim.13156\u003c/span\u003e\u003cspan address=\"10.1111/joim.13156\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYepez JB, Murati FA, Petitto M, et al. Vogt-Koyanagi-Harada Disease Following COVID-19 Infection. Case Rep Ophthalmol. Sep-Dec 2021;12(3):804\u0026ndash;808. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1159/000518834\u003c/span\u003e\u003cspan address=\"10.1159/000518834\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMohd-Alif WM, Nur-Athirah A, Hanapi MS, Tuan Jaffar TN, Shatriah I. Bilateral and Multiple Central Serous Chorioretinopathy Following COVID-19 Infection: A Case Report and Literature Review. Cureus. Mar 2022;14(3):e23246. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7759/cureus.23246\u003c/span\u003e\u003cspan address=\"10.7759/cureus.23246\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAgarwal M, Sachdeva M, Pal S, et al. Endogenous Endophthalmitis A Complication of COVID-19 Pandemic: A Case Series. Ocul Immunol Inflamm. May 19 2021;29(4):726\u0026ndash;729. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/09273948.2021.1945111\u003c/span\u003e\u003cspan address=\"10.1080/09273948.2021.1945111\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNishiyama T, Tsujinaka H, Mizusawa Y, et al. Acute retinal necrosis in a patient on immunosuppressive treatment for COVID-19 pneumonia: a case report. BMC Ophthalmol. Nov 30 2022;22(1):462. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12886-022-02692-5\u003c/span\u003e\u003cspan address=\"10.1186/s12886-022-02692-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaur R, Khan B, Sharma A. Optical Coherence Tomography of Retinal Artery Occlusion Associated With Mucormycosis and COVID-19. JAMA Ophthalmol. Nov 1 2021;139(11):e214064. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamaophthalmol.2021.4064\u003c/span\u003e\u003cspan address=\"10.1001/jamaophthalmol.2021.4064\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDubey S, Mukherjee D, Sarkar P, et al. COVID-19 associated rhino-orbital-cerebral mucormycosis: An observational study from Eastern India, with special emphasis on neurological spectrum. Diabetes Metab Syndr. Sep-Oct 2021;15(5):102267. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.dsx.2021.102267\u003c/span\u003e\u003cspan address=\"10.1016/j.dsx.2021.102267\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHufendiek K, Gamulescu MA, Hufendiek K, et al. Classification and characterization of acute macular neuroretinopathy with spectral domain optical coherence tomography. Int Ophthalmol. Dec 2018;38(6):2403\u0026ndash;2416. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10792-017-0742-9\u003c/span\u003e\u003cspan address=\"10.1007/s10792-017-0742-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFawzi AA, Pappuru RR, Sarraf D, et al. Acute macular neuroretinopathy: long-term insights revealed by multimodal imaging. Retina. Sep 2012;32(8):1500\u0026ndash;13. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/IAE.0b013e318263d0c3\u003c/span\u003e\u003cspan address=\"10.1097/IAE.0b013e318263d0c3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFekri S, Khorshidifar M, Dehghani MS, et al.Acute macular neuroretinopathy and COVID-19 vaccination: Case report and literature review. J Fr Ophtalmol. Jan 2023;46(1):72\u0026ndash;82. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jfo.2022.09.008\u003c/span\u003e\u003cspan address=\"10.1016/j.jfo.2022.09.008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePowers JH, Singh PP, Grewal DS, et al. Multimodal imaging of type 2 acute macular neuroretinopathy in a young woman. Digit J Ophthalmol. 2021;27(3):44\u0026ndash;47. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.5693/djo.02.2021.06.004\u003c/span\u003e\u003cspan address=\"10.5693/djo.02.2021.06.004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGupta N, Padidam S, Tewari A. Acute macular neuroretinopathy (AMN) related to energy drink consumption. BMJ Case Rep. Dec 15 2019;12(12)doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bcr-2019-232144\u003c/span\u003e\u003cspan address=\"10.1136/bcr-2019-232144\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAshfaq I, Vrahimi M, Waugh S, et al. Grinton ME, Browning AC. Acute Macular Neuroretinopathy Associated with Acute Influenza Virus Infection. Ocul Immunol Inflamm. Feb 17 2021;29(2):333\u0026ndash;339. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/09273948.2019.1681470\u003c/span\u003e\u003cspan address=\"10.1080/09273948.2019.1681470\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDutta Majumder P, Agarwal A. Acute Macular Neuroretinopathy and Paracentral Acute Middle Maculopathy during SARS-CoV-2 Infection and Vaccination. Vaccines (Basel). Feb 17 2023;11(2)doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/vaccines11020474\u003c/span\u003e\u003cspan address=\"10.3390/vaccines11020474\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRadwan LM, Bou Ghanem GO, Daye GN, et al.Acute macular neuroretinopathy associated with intravitreal anti-VEGF injection: A case report. Am J Ophthalmol Case Rep. Dec 2022;28:101687. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ajoc.2022.101687\u003c/span\u003e\u003cspan address=\"10.1016/j.ajoc.2022.101687\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuardiola GA, Villegas VM, Cruz-Villegas V, et al.Acute macular neuroretinopathy in dengue virus serotype 1. Am J Ophthalmol Case Rep. Mar 2022;25:101250. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ajoc.2021.101250\u003c/span\u003e\u003cspan address=\"10.1016/j.ajoc.2021.101250\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBos PJ, Deutman AF. Acute macular neuroretinopathy. Am J Ophthalmol. Oct 1975;80(4):573\u0026ndash;84. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/0002-9394(75)90387-6\u003c/span\u003e\u003cspan address=\"10.1016/0002-9394(75)90387-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBhavsar KV, Lin S, Rahimy E, et al. Acute macular neuroretinopathy: A comprehensive review of the literature. Surv Ophthalmol. Sep-Oct 2016;61(5):538\u0026ndash;65. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.survophthal.2016.03.003\u003c/span\u003e\u003cspan address=\"10.1016/j.survophthal.2016.03.003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLains I, Wang JC, Cui Y, et al. Retinal applications of swept source optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). Prog Retin Eye Res. Sep 2021;84:100951. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.preteyeres.2021.100951\u003c/span\u003e\u003cspan address=\"10.1016/j.preteyeres.2021.100951\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKulikov AN, Maltsev DS, Leongardt TA. Retinal Microvasculature Alteration in Paracentral Acute Middle Maculopathy and Acute Macular Neuroretinopathy: A Quantitative Optical Coherence Tomography Angiography Study. Retin Cases Brief Rep. Fall 2020;14(4):343\u0026ndash;351. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/ICB.0000000000000709\u003c/span\u003e\u003cspan address=\"10.1097/ICB.0000000000000709\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDu L, Kijlstra A, Yang P. Vogt-Koyanagi-Harada disease: Novel insights into pathophysiology, diagnosis and treatment. Prog Retin Eye Res. May 2016;52:84\u0026ndash;111. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.preteyeres.2016.02.002\u003c/span\u003e\u003cspan address=\"10.1016/j.preteyeres.2016.02.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen X, Li X, Li H, et al. Ocular Adverse Events after Inactivated COVID-19 Vaccination in Xiamen. Vaccines (Basel). Mar 21 2022;10(3)doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/vaccines10030482\u003c/span\u003e\u003cspan address=\"10.3390/vaccines10030482\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoenigl M, Seidel D, Carvalho A, et al. The emergence of COVID-19 associated mucormycosis: a review of cases from 18 countries. Lancet Microbe. Jul 2022;3(7):e543-e552. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S2666-5247(21)00237-8\u003c/span\u003e\u003cspan address=\"10.1016/S2666-5247(21)00237-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\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":"Retina, COVID-19, Acute macular neuroretinopathy, Multimodal Imaging, SARS-CoV-2","lastPublishedDoi":"10.21203/rs.3.rs-4005199/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4005199/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTo define the characteristics of fundus manifestations in patients after SARS-Cov-2 infection with multimodal imaging techniques.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis is a retrospective multicenter and multimodal imaging study including 90 patients. All patients with a visual complaint occurring immediately after SARS-Cov-2 infection were referred to six clinics between December 2022 and February 2023. Demographic information and the temporal relationship between SARS-Cov-2 infection and visual symptoms were documented. The characteristics of the fundus lesions were evaluated using multimodal imaging.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eNinety patients from six hospitals were enrolled in this study, including 24 males (26.67%) and 66 (73.33%) females. Seventy-eight patients (86.66%) (146 eyes) were diagnosed with AMN. The AMN patients were primarily young women (67.95%). Sixty-eight patients (87.18%) had AMN in both eyes. Thirty-eight eyes (24.36%) included Purtscher or Purtscher-like lesions. optical coherence tomography and infrared retinal photographs can show AMN lesions well. Eleven cases were diagnosed with simple Purtscher or Purtscher-like retinopathy (2 cases, 2.22%), VKH or VKH-like uveitis (3 cases, 3.33%), MEWDS (2 cases, 2.22%), and ROCM (5 cases, 5.56%).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eAfter SARS-Cov-2 infection, diversified fundus lesions were evident in patients with visual complaints. In this report, AMN was the dominant manifestation, followed by Purtscher or Purtscher-like retinopathy, MEWDS, VKH-like uveitis, and ROCM.\u003c/p\u003e","manuscriptTitle":"Rare Fundus Lesions in Patients after SARS-Cov-2 Infection: A Multicenter and Multimodal Imaging Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-20 17:45:12","doi":"10.21203/rs.3.rs-4005199/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-05-20T05:06:54+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-08T19:06:31+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-01T18:20:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"cc201595-c590-4c3c-94a2-0b190b52a413","date":"2024-04-27T13:10:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"26d76363-4b23-4b67-93d3-3aa1b74117ad","date":"2024-04-27T06:12:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"e03b0f99-392b-4e51-acc5-2cab03f3e7ed_SNPRID","date":"2024-04-19T10:03:13+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-04-19T09:43:43+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-17T06:00:46+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-03-18T13:07:51+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-03-15T10:18:34+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-03-02T02:25:15+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":"1bfbde66-a4ab-44f4-a5f9-e1f6caa0869d","owner":[],"postedDate":"March 20th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":29599089,"name":"Health sciences/Diseases/Eye diseases/Eye abnormalities"},{"id":29599090,"name":"Health sciences/Diseases/Eye diseases/Retinal diseases"},{"id":29599091,"name":"Health sciences/Diseases/Eye diseases/Vision disorders"}],"tags":[],"updatedAt":"2024-06-18T06:27:22+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-20 17:45:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4005199","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4005199","identity":"rs-4005199","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}