Acute macular neuroretinopathy and COVID-19 or SARS-CoV-2 infection: case report and literature review

Purpose To describe a case of acute macular neuroretinopathy (AMN) associated with COVID-19 infection and a related literature review. Methods A case from the First Affiliated Hospital of Chongqing Medical University was reported that could be linked to COVID-19 or SARS-CoV-2 infection. We performed a comprehensive search on PubMed, retrieving articles containing information on AMN after COVID-19 or SARS-CoV-2 infection. The key words used were ‘COVID-19’, ‘SARS-CoV-2’, ‘ophthalmic manifestations’, ‘acute macular neuroretinopathy’, and ‘paracentral scotomas’. The relevant data were extracted, charted, consolidated, and evaluated. Moreover, manual exploration of the reference lists of pertinent articles was carried out. Results We describe the case of a 30-year-old young woman who developed bilateral AMN one day after being infected with COVID-19 or SARS-CoV-2. She had severe visual impairment (20/2000 OD and 20/32 OS), and her vision recovered after taking oral corticosteroids. After reviewing the literature, we summarized 16 relevant reports and found that symptoms of AMN tend to arise 1 day to 1 month after COVID-19 or SARS-CoV-2 infection. Contraceptive pills and other risk factors should be avoided to reduce the risk of adverse outcomes. Oral prednisone may be an effective treatment for those experiencing important vision loss. Conclusion Symptoms of AMN can arise 1 day to 1 month after COVID-19 or SARS-CoV-2 infection. Ophthalmologists should remain vigilant about this disease, notably because patient characteristics may deviate from the norm.


Methods
Patient signed informed consent forms.This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Chongqing Medical University, the First Affiliated Hospital of Chongqing Medical University (Approval No. 2023-181).A PubMed database search was performed for 'COVID-19' , 'SARS-CoV-2' , 'ophthalmic manifestations' , 'acute macular neuroretinopathy' , and 'paracentral scotomas' .The reference lists of the obtained records were manually searched for additional reports.We included articles in the English language published between January 1, 2020, and March 31, 2023.There were no restrictions on study design, but duplicate reports were removed.The extracted data included patient demographic information, drug history, background conditions, COVID-19 or SARS-CoV-2 infection symptoms, infection-to-ocular symptom time intervals, symptom presentations, findings from imaging studies, treatment processes, and outcomes.While the search was not exhaustive, we tried to include all the articles.

Case presentation
A 30-year-old Han woman complained of blurred vision in both eyes (more evident in the right eye) one day after the symptoms of COVID-19 or SARS-CoV-2 infection, i.e., fever (39.1°C), first appeared.The infection was diagnosed by reverse transcriptase polymerase chain reaction (PCR).Her visual acuity was 20/2000 OD and 20/32 OS.No relative afferent pupillary defect (RAPD) was found.No anterior segment abnormalities were detected.Color fundus imaging demonstrated perifoveal reddish-brown lesions OUs (Figure 1A).Near-infrared reflectance (NIR) imaging in both eyes revealed a well-demarcated, hyporeflective, oval-shaped macular lesion involving the fovea and that extended nasally, with the lesion area in the right eye being approximately three times that in the left eye (Figures 1B,C).Cross-sectional spectral-domain OCT (SD-OCT) revealed outer plexiform layer (OPL) thickening, outer nuclear layer (ONL) thinning, and disruption of the ellipsoid zone (EZ) in areas corresponding to the lesions (OU) (Figures 1B,C).She had no known ocular history, or systemic condition, and had not sought treatment prior to this presentation.
Given the acute development of these characteristic findings along with her clinical history, the patient was diagnosed with AMN.She was started on oral prednisolone 30 mg/day for 7 days.Afterward, the dose was reduced to 10 mg per week until 5 mg/day, after which the treatment was stopped.Notably, by one month, her visual acuity was 20/20 OD and 20/20 OS.During the four-month follow-up period, the patient's visual acuity stabilized at 20/20, and no further discomfort was reported in either eye.

Literature search results
In the literature, we found 19 articles reporting cases of AMN in people with recent COVID-19 or SARS-CoV-2 infection (see Table 1).

Discussion
At present, COVID-19 or SARS-CoV-2 infection can be asymptomatic or cause mild influenza-like symptoms, and severe cases can present with respiratory distress and multiple organ failure.COVID-19 or SARS-CoV-2 seems to employ mechanisms for receptor recognition.It can bind with angiotensin-converting enzyme 2 (ACE-2) with the assistance of transmembrane serine protein 2 (TMPRSS2) or enter host cells by binding with the CD147 spike protein, thereby triggering a series of symptoms (29).ACE-2 receptors are present in the retinal ganglion cell layer, inner plexiform layer,   (30).Endothelial damage and microthrombi are the main pathological changes that lead to ocular disease.Ophthalmologists worldwide have reported various manifestations of infection in the eye.Ophthalmic images vary in terms of presentation, severity, and timing (31).COVID-19 or SARS-CoV-2 can directly cause damage via keratoconjunctivitis, epiphora, or chemosis.Hyperinflammation with cytokine storms, stasis with hypoxia, and stasis with hypoxia that activate coagulation mechanisms can cause retinal disease (7,8,31,32).Elevated D-dimer, serum ferritin, and lactate dehydrogenase levels and increased ESR/CRP inflammatory marker levels are observed in patients with ocular manifestations even after recovering from COVID-19 (33).
According to the available literature, symptoms of AMN can arise 1 day to 1 month after COVID-19 or SARS-CoV-2 infection.Risk factors such as contraceptive pills should be avoided.Oral prednisone may be an effective treatment for those experiencing marked vision loss.It is crucial to conduct additional research to uncover a potential cause-and-effect relationship between AMN and COVID-19 or SARS-CoV-2.However, whether a genetic susceptibility exists is unknown.To reinforce this hypothesis, further investigations with a larger sample size, including individuals with and without ocular symptoms and incorporating prolonged follow-up times are needed.As the pandemic continues and vaccination programs are rolled out extensively, the number of AMN cases may increase.Ophthalmologists should remain vigilant about this disease, notably because patient characteristics may deviate from the norm.

FIGURE 1
FIGURE 1 Multimodal images that display a partial reconstitution of the outer retinal architecture.(A) Fundus photographs of the right (OD) and left (OS) eyes at the time of presentation.(B,C) SD-OCT images of both eyes.

TABLE 1
Cases of AMN associated with COVID-19 or SARS-CoV-2 infection., and outer photoreceptor segments of the eye.Moreover, TMPRSS2 is expressed in multiple retinal neuronal cells, vascular and perivascular cells, and retinal Müller glial cells.SARS-CoV-2 RNA was found in the retinas of patients who died from COVID-19, suggesting viral entry into retinal cells