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JAMA Ophthalmology Clinical Challenge
December 8, 2022

Seeing Blue Dots After COVID-19 Infection

Author Affiliations
  • 1Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota
JAMA Ophthalmol. 2023;141(1):97-98. doi:10.1001/jamaophthalmol.2022.5235

Case

A healthy 12-year-old female individual received a diagnosis of SARS-CoV-2 and reported visual symptoms 2 days later, with bilateral blurry vision, large blue paracentral scotomata, and a migraine without a scintillating scotoma. On clinical examination, visual acuity measured 20/70 + 1 in the right eye and 20/100 in the left eye, while she previously had visual acuity of 20/25 in each eye on examination 8 years prior. Motility, visual fields, and anterior segment examination results were normal. Dilated fundus examination revealed subtle reddish geographic irregularities at the level of the retinal pigment epithelial at a nasal juxtafoveal location in both eyes. The optic discs, vessels, and periphery were normal. Near-infrared (IR) imaging highlighted the irregularities in both eyes (Figure 1).

Figure 1.  
Near-infrared imaging of the right eye (A) and left eye (B) demonstrates juxtafoveal irregularity. The foveal regions have subtle juxtafoveal geographic areas (white arrowheads), mostly nasal to the foveal center in both eyes (A > B).

Near-infrared imaging of the right eye (A) and left eye (B) demonstrates juxtafoveal irregularity. The foveal regions have subtle juxtafoveal geographic areas (white arrowheads), mostly nasal to the foveal center in both eyes (A > B).

Box Section Ref ID

What Would You Do Next?

  1. Genetic testing

  2. Electroretinogram

  3. Optical coherence tomography

  4. Fluorescein angiography

Discussion

Diagnosis

COVID-19–associated acute macular neuroretinopathy

What to Do Next

C. Optical coherence tomography

Discussion

Optical coherence tomography (OCT) and IR images can be useful imaging modalities to detect acute macular neuroretinopathy (AMN). Findings include a circular dark lesion on IR images. On transverse OCT images, outer nuclear layer hyperreflectivity combined with interdigitation zone hyporeflectivity (Figure 2) correspond to the dark geographic lesions seen with IR imaging (Figure 1). Lesions correspond subjectively to the central or paracentral, partial-depth scotoma. While the fundus examination results may remain normal for up to 2 months after the onset of symptoms, changes are usually detected early using multimodal imaging. The fluorescein angiography results are in approximately 70% of AMN cases, may demonstrate subtle hypofluorescence in 20% of lesions, or may demonstrate hypofluorescence only in the late phase in the remaining 10% of lesions. Similarly, electroretinogram results are normal in most cases (90%), and 10% will have reduced a-wave amplitudes.1 Multifocal electroretinogram has also been proposed and shows focal wave-form abnormalities.2

Figure 2.  
A, Near-infrared image of the left eye. B, Hyporeflectivity in the ellipsoid zone and photoreceptor layers (between arrowheads). There is subtle hyperreflectivity at the outer nuclear layer (between arrowheads). OCT indicates optical coherence tomography.

A, Near-infrared image of the left eye. B, Hyporeflectivity in the ellipsoid zone and photoreceptor layers (between arrowheads). There is subtle hyperreflectivity at the outer nuclear layer (between arrowheads). OCT indicates optical coherence tomography.

Acute macular neuroretinopathy is a microvascular, neuroretinal condition originally described by Bos and Deutman3 that presents with paracentral scotomas and corresponding dark-reddish, wedge-shaped, intraretinal lesions. The OCT from patients with AMN changes rapidly during the first few weeks, with findings including discontinuity of the outer retinal layers, ellipsoid zone loss, and thinning of outer nuclear layer.4 Acute macular neuroretinopathy has been associated with several precipitating factors, including upper respiratory tract viral infection, influenza, intravenous contrast, intravenous epinephrine, and preeclampsia. Acute macular neuroretinopathy is usually bilateral and common in White female individuals during the third decade of life.1 The pathogenesis of AMN is not well understood. Fawzi et al4 hypothesized that AMN is associated with microvascular ischemia in the deep retinal capillary plexus. Visual symptoms persist long term in 54% of patients with AMN, while up to 29% experience some improvement (outcome unknown in the remainder of cases).5

To our knowledge, 16 cases of AMN in patients with COVID-19 have been reported, all in adults aged 21 to 71 years (mean age, 26 years). The median time from onset of symptoms to diagnosis was 17 days, ranging from 4 to 35 days.6-10 To our knowledge, no cases of SARS-CoV-2 associated with AMN have been reported in a child (younger than 18 years). The association of symptomatic SARS-CoV2 with new onset of AMN findings could be consistent with a causal link.6,7

Patient Outcome

The patient returned 1 month after her initial diagnosis with persistent, yet less symptomatic paracentral blue scotoma. Best-corrected visual acuity improved to 20/20 in each eye. A hypercoagulability test panel (prothrombin G20210A, protein S, protein C, antithrombin, D-dimer, fibrinogen, thrombin time, dilute Russell Viper Venom time, activated partial thromboplastin clotting time, international normalized ratio, and prothrombin time) yielded normal results. Repeated OCT showed a more normal reflectivity at the interdigitation zone.

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Article Information

Corresponding Author: Timothy W. Olsen, MD, Department of Ophthalmology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905 (olsen.timothy@mayo.edu).

Published Online: December 8, 2022. doi:10.1001/jamaophthalmol.2022.5235

Conflict of Interest Disclosures: Dr Olsen reported being the founder of iMacular Regeneration, LLC and serving as the Secretary for Quality of Care at the American Academy of Ophthalmology. No other disclosures were reported.

Additional Contributions: We thank the patient and her family for granting permission to publish this information.

References
1.
Bhavsar  KV, Lin  S, Rahimy  E,  et al.  Acute macular neuroretinopathy: a comprehensive review of the literature.   Surv Ophthalmol. 2016;61(5):538-565. doi:10.1016/j.survophthal.2016.03.003 PubMedGoogle ScholarCrossref
2.
Browning  AC, Gupta  R, Barber  C, Lim  CS, Amoaku  WM.  The multifocal electroretinogram in acute macular neuroretinopathy.   Arch Ophthalmol. 2003;121(10):1506-1507. doi:10.1001/archopht.121.10.1506PubMedGoogle ScholarCrossref
3.
Bos  PJ, Deutman  AF.  Acute macular neuroretinopathy.   Am J Ophthalmol. 1975;80(4):573-584. doi:10.1016/0002-9394(75)90387-6 PubMedGoogle ScholarCrossref
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Fawzi  AA, Pappuru  RR, Sarraf  D,  et al.  Acute macular neuroretinopathy: long-term insights revealed by multimodal imaging.   Retina. 2012;32(8):1500-1513. doi:10.1097/IAE.0b013e318263d0c3 PubMedGoogle ScholarCrossref
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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(21):5038. doi:10.3390/jcm10215038 PubMedGoogle ScholarCrossref
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Jalink  MB, Bronkhorst  IHG.  A sudden rise of patients with acute macular neuroretinopathy during the COVID-19 pandemic.   Case Rep Ophthalmol. 2022;13(1):96-103. doi:10.1159/000522080 PubMedGoogle ScholarCrossref
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Masjedi  M, Pourazizi  M, Hosseini  N-S.  Acute macular neuroretinopathy as a manifestation of coronavirus disease 2019: a case report.   Clin Case Rep. 2021;9(10):e04976. doi:10.1002/ccr3.4976 PubMedGoogle ScholarCrossref
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Preti  RC, Zacharias  LC, Cunha  LP, Monteiro  MLR.  Acute macular neuroretinaopathy as the presenting manifestation of COVID-19 infection.   Retin Cases Brief Rep. 2022;16(1):12-15. doi:10.1097/ICB.0000000000001050 PubMedGoogle ScholarCrossref
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David  JA, Fivgas  GD.  Acute macular neuroretinopathy associated with COVID-19 infection.   Am J Ophthalmol Case Rep. 2021;24:101232. doi:10.1016/j.ajoc.2021.101232 PubMedGoogle ScholarCrossref
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