Acute macular neuroretinopathy associated with COVID-19 pandemic, study reports

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A newly published Chinese study found increased numbers of cases with acute macular neuroretinopathy (AMN) and other deficits associated with the COVID-19 outbreak,¹ reported Xiaojia Song, MD, from the Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing, China, and the Department of Ophthalmology, Qilu Hospital of Shandong University (Qingdao), Qingdao, Shandong, China.

The investigators explained that AMN, a rare disease, is characterized by dark reddish, wedge-shaped macular lesions.² Impairment of the retinal deep capillary plexus also occurs and suggests ischemia,^3,4 although the exact etiology remains unclarified.²

“Immediately following the cessation of the zero-COVID policy in China at the end of 2022, a significant outbreak of COVID-19 occurred in mainland China, coinciding with an unforeseen surge in clinically diagnosed cases of AMN. While numerous authors have reported AMN following COVID-19, instances of large gatherings have been scarcely documented, let alone within an extraordinarily brief timeframe,”^5-7 the authors said.

They explained further that severe SARS-CoV-2 infection induces inflammatory storms and hypercoagulation, leading to multisystem dysfunctions, such as acute pulmonary embolism, deep vein thrombosis, ischemic stroke, myocardial infarction, and arterial embolism.^8,9 AMN, paracentral acute middle maculopathy (PAMM), and Purtscher-like retinopathy represent a spectrum of distal retinal vasculopathies, and also have been associated with COVID-19 in sporadic case reports.^6,10,11

The prospective observational study under discussion recruited patients in northern China with AMN who had the SARS-CoV-2 Omicron variant, and the researchers analyzed their clinical and retinal imaging features.

Each patient in the study underwent color fundus photography, near-infrared imaging, swept-source optical coherence tomography (SS-OCT), OCT angiography (OCTA), and Humphrey perimetry.

Findings of the analysis

The authors prospectively recruited 12 men and 21 women, the majority (87.88%) of whom were affected bilaterally. The median time from the onset of fever and the appearance of ocular symptoms was 2 days (range, 0.5–5.0 days).

In addition to the typical changes in the outer retina seen in AMN, Song and colleagues also reported changes in the inner retinal layers, including intraretinal hemorrhage (8.06%), cotton wool spots (9.68%), and paracentral PAMM (8.06%). Smaller retinal inner nuclear layer hyperreflective speckles (RIHS) (41.94%) distinguished the feature from the typical findings in PAMM.

OCTA showed that the superficial (11.54%), intermediate (82.69%), deep capillary plexus (98.08%), and choriocapillaris (19.23%) had voids of vessel signals. Humphrey perimetry showed central, paracentral, and peripheral scotomas. The occult lesions associated with AMN, PAMM, and some of the RIHS seen on OCT images were visualized topographically and further confirmed by OCTA as perfusion defects, they reported.

The investigators concluded, “The current study describes the emergence of AMN following the surge of COVID-19 cases during the pandemic in China. Almost all individuals in our case series presented visual symptoms closely related to the acute primary SAR-CoV-2 Omicron infection. A high frequency of bilateral ocular changes and a less pronounced female predominance were observed among our patients. The retinal alterations in those patients included typical outer retinal changes consistent with AMN, as well as choriocapillaris perfusion deficits and extensively distributed inner retinal changes.”

They continued, “These findings contribute to the unique ocular manifestations observed in COVID-19. The presence of isolated, delicate, and randomly located RIHS suggests widespread inner retinal insults that may differ from PAMM in pathogenesis, where flow insufficiency plays a major role. The perfusion deficits identified on OCTA may serve as supportive evidence and potential biomarkers for widespread ischemia and systemic microcirculation dysregulation in COVID-19. Further research is necessary to better understand the role of the SAR-CoV-2 Omicron variant in the pathophysiology processes underlying retinopathy.”

References:

1. Song X, Yu Y, Zhou H, et al. Acute macular neuroretinopathy associated with covid-19 pandemic: a real-world observation study. Asia Pac J Ophthalmol. 2024;13; https://doi.org/10.1016/j.apjo.2024.100103

2. Fawzi AA, Pappuru RR, Sarraf D, et al. Acute macular neuroretinopathy: long-term insights revealed by multimodal imaging. Retina. 2012;32:1500-1513.

3. Cabral D, Ramtohul P, Zatreanu L, et al. Deep capillary plexus features in acute macular neuroretinopathy: novel insights based on the anatomy of Henle fiber layer. Invest Ophthalmol Vis Sci. 2022;63:4.

4. Giacuzzo C, Eandi CM, Kawasaki A.Bilateral acute macular neuroretinopathy following COVID-19 infection. Acta Ophthalmol. 2022;100:e611-e612.

5. Azar G, Bonnin S, Vasseur V, et al.Did the COVID-19 pandemic increase the incidence of acute macular neuroretinopathy?J Clin Med. 2021;10: 5038.

6. Dinh RH, Tsui E, Wieder MS, et al.Acute macular neuroretinopathy and coronavirus disease 2019.Ophthalmol Retin. 2023;7:198-200.

7. Lin TPH, Sen M, Gupta V, et al.Update on coronavirus disease 2019: ophthalmic manifestations and adverse reactions to vaccination. Asia Pac J Ophthalmol (Philos). 2023;12:512-536.

8. Ye Q, Wang B, Mao J.The pathogenesis and treatment of the 'cytokine storm' in COVID-19. J Infect. 2020;80:607-613.

9. Abou-Ismail MY, Diamond A, Kapoor S, et al.The hypercoagulable state in COVID-19: incidence, pathophysiology, and management. Thromb Res. 2020;194:101-115.

10. Virgo J, Mohamed M.Paracentral acute middle maculopathy and acute macular neuroretinopathy following SARS-CoV-2 infection. Eye (Lond). 2020;34:2352-2353.

11. Fang L, Tian T, Zhuang S, et al.Acute macular neuroretinopathy after coronavirus disease 2019 infection. Ophthalmol Retin. 2024;8:409-414.