Acute Macular Neuroretinopathy (AMN) in Young Healthy Patients During the COVID-19 Pandemic

The COVID-19 pandemic caused by the SARS-CoV-2 coronavirus has been a global health crisis for the past three years. At the time of writing this paper, the Omicron variant was the most notable and widespread, posing significant challenges in controlling its spread compared to the initial Alpha or Delta variants.

Since the easing of epidemic control measures for COVID-19 in China in December 2022, the pandemic has rapidly spread within the country. Recent reports have highlighted a wide range of ocular manifestations associated with the disease, including conjunctivitis, scleritis, acute anterior uveitis, various retinal/choroid manifestations, and neuro-ophthalmologic manifestations.

These ocular symptoms have occasionally involved extraocular motility, cranial nerves, and orbital/ocular adnexa [1].

Acute macular neuroretinopathy (AMN) is a rare retinal microvascular disorder characterized by the sudden onset of brownish-red, wedge-shaped (or petaloid) perifoveal lesions that cause paracentral or central scotomas. The prevalence of AMN has been reported to be less than 1 patient per million [2].

However, an increasing number of cases have been observed with the wider application of multi-model imaging. AMN is commonly seen in young females and has been associated with various risk factors such as flu-like illness, hormonal oral contraceptive pills, antecedent trauma, caffeine, epinephrine and pseudoephedrine injection, hypovolemia, and pregnancy-induced hypertension [3].

There has been speculation regarding the association between AMN and SARS-CoV-2 infection, as there have been reports of a surge in AMN incidence during the COVID-19 pandemic or following COVID-19 vaccinations [4–7].

Case Series and Discussions

In this article, we present a case series of AMN in young healthy patients during the first surge of SARS-CoV-2 infection, immediately after the easing of epidemic control measures in Wuhan, China, in December 2022. These patients were referred to Union Hospital, Tongji Medical College shortly after the viral infection. Unusually, the first three cases were presented on the same day, which is atypical for this rare disease.

AMN is characterized by the sudden onset of paracentral scotomas, and it is most commonly observed in young females. The disease has been associated with various risk factors, but its exact pathogenesis is not fully understood. The most common pathogenesis is thought to be ischemia of the deep retinal capillary plexus.

Imaging techniques such as infra-red or red-free photography and optical coherence tomography (OCT) have helped identify characteristic wedge-shaped parafoveal lesions and hyperreflectivity of the outer nuclear and plexiform layers [8]. However, in the cases reported here, OCT angiography (OCTA) did not reveal remarkable changes in the retinal or choroidal capillary plexus, except in one case with perfusion defects. Other imaging modalities such as fundus autofluorescence (FAF) and visual evoked potentials (VEP) provided additional insights into the disease presentation.

The possible association between AMN and SARS-CoV-2 infection remains speculative. SARS-CoV-2 is known to enter host cells through the interaction of its spike protein with the angiotensin-converting enzyme (ACE)-2 receptor, which is found in various retinal layers. Additionally, the transmembrane serine protease (TMPRSS2), required for viral entry, is also present in retinal cells.

Although no conclusive evidence of viral presence in the retina has been reported in these cases, SARS-CoV-2 RNA has been detected in the retina of some COVID-19 patients who died [10, 11]. The proposed mechanism for AMN development after SARS-CoV-2 infection involves acute vascular events, inflammation, and subsequent ischemia of the deep retinal capillary plexus and choroidal capillary.

Hyperinflammatory responses and thromboembolic events, leading to endothelial damage, may contribute to AMN induced by SARS-CoV-2 [12]. OCT findings of hyperreflectivity in the outer retina, accompanied by ellipsoid and interdigitation zone disruption, suggest adjacent photoreceptor and retinal pigment epithelium damage. Corresponding flow voids observed in OCTA scans may indicate capillary perfusion defects [9].

Currently, there is no established treatment guideline for AMN associated with SARS-CoV-2 infection or vaccination. The course of AMN can vary from self-limiting to persisting for weeks or months, with diverse outcomes ranging from persistent scotomas to complete visual recovery [13–17]. Some cases have been managed with corticosteroid therapy, either for a short time or for a longer period, resulting in varying outcomes [18–20].

In the cases reported here, early administration of prednisone followed by a gradual tapering over a 2-month period was performed. During follow-up, OCT revealed resolution of hyperreflective lesions, but subsequent loss of ellipsoid and interdigitation zones was observed. Visual acuity remained unchanged in most cases, with persisting scotomas. However, one case showed remarkable improvement in visual acuity and resolution of lesions on OCT after prednisone administration.

Furthermore, a correlation between COVID-19 vaccination and AMN has been observed in recent reports. Several cases of AMN have been reported shortly after COVID-19 vaccinations [21–24], suggesting a potential causal relationship. However, further investigation is required to establish a definitive association.

Conclusion

This case series highlights the occurrence of AMN in young healthy patients during the first surge of SARS-CoV-2 infection after the easing of epidemic control measures in Wuhan, China. The association between AMN and SARS-CoV-2 infection or vaccination remains speculative but warrants further investigation. Imaging techniques such as OCT and OCTA have provided valuable insights into the characteristic features of AMN, including hyperreflectivity of retinal layers and capillary perfusion defects.

The management of AMN in the context of SARS-CoV-2 infection or vaccination requires further study, as treatment outcomes vary. Continuous monitoring and long-term follow-up are necessary to understand the course and prognosis of AMN in relation to the COVID-19 pandemic.

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reference link : https://www.tandfonline.com/doi/full/10.2147/JIR.S413050