Coronavirus Disease 2019–Associated Ocular Neuropathy With Panuveitis: A Case Report | Neurology | JAMA Ophthalmology | JAMA Network
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December 17, 2020

Coronavirus Disease 2019–Associated Ocular Neuropathy With Panuveitis: A Case Report

Author Affiliations
  • 1Ophthalmology Department, Metz-Thionville Regional Hospital Center, Lorraine University, Mercy Hospital, Metz, France
JAMA Ophthalmol. 2021;139(2):247-249. doi:10.1001/jamaophthalmol.2020.5695

In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared in Wuhan, China. The SARS-CoV-2 virus affects the lungs and other organs and has many different clinical manifestations. Regarding the eye, SARS-CoV-2 is well known to induce conjunctivitis; for example, in a study1 of 38 consecutive patients with coronavirus disease 2019 (COVID-19), 5% had virus-positive conjunctivae and 32% had conjunctivitis. However, whether SARS-CoV-2 can cause significant ocular disease is unknown.2

Here we report a case of COVID-19 with severe ocular neuropathy and panuveitis. This case has not been reported previously and has been approved by the ethics committee of the French Society of Ophthalmology. Written informed consent has been obtained from the patient.

Report of a Case

In March 2020, a woman in her late 50s was hospitalized for severe bilateral pneumonia. Coronavirus disease 2019 was suspected because of recent close contact with a fatal COVID-19 case. A nasopharyngeal swab reverse-transcription–polymerase chain reaction test had positive results for SARS-CoV-2.

On day 2 postadmission, the patient developed blurred vision and redness in her right eye and temporary (8-day) pain when mobilizing the globe. Her best-corrected visual acuity was +2 logMAR (hand movement) OD and 0 logMAR OS. The right eye had a relative afferent pupil defect, central scotoma, and impaired color and contrast vision. A slitlamp examination revealed central nongranulomatous retrodescemetic precipitates and mild anterior chamber inflammation. A fundus examination revealed noticeable pupillary edema, 2 peripapillary hemorrhages, mild vitreous inflammation, and retinal vessel narrowing in the inferior retina. Contralateral eye examinations had normal results.

Other neurological symptoms were not observed, including muscle weakness, sensory loss, and superficial temporal arteritis. There was no relevant medical history.

Extensive differential diagnostic testing showed normal complete blood cell counts, serum angiotensin-converting enzyme levels, and human leukocyte antigen B51/B27 typing, and negative results for syphilis, HIV, Toxoplasma gondii, and Borrelia serologies. Varicella-zoster virus, herpes simplex virus, Epstein-Barr virus, and cytomegalovirus serologies had negative results for IgM and very weakly positive results for IgG.

Because of the blurred vision, cranial magnetic resonance imaging with fine optic nerve cuts (T1-weighted, T2-weighted, fat saturation, and fluid-attenuated inversion recovery T2, before and after intravenous gadolinium) and a lumbar puncture with a SARS-CoV-2 reverse-transcription–polymerase chain reaction test of the cerebrospinal fluid were conducted. Both had negative results.

The patient was treated with oral and topical corticosteroids for presumed noninfectious ocular inflammation. On day 30, when the patient could be moved, fluorescein angiography revealed optic disc neuritis (Figure 1A) and inferior retinal vasculitis (Figure 1B). Mild papillary edema was observed (Figure 2A). Inflammation-induced ocular neuropathy associated with SARS-CoV-2–induced panuveitis was diagnosed.

Figure 1.  Fluorescein Angiography of the Right Eye on Day 30 Postadmission
Fluorescein Angiography of the Right Eye on Day 30 Postadmission

A, Optic disc neuritis was observed along with mild leakage that associated with an inferior peripapillary hemorrhage (arrowhead). B, Fluorescein leakage from retinal venules inferotemporal to the macula was also observed (arrowheads). This eye examination could only be performed on day 30 because the patient was initially hospitalized in intensive care and could not be moved.

Figure 2.  Evolution of Papillitis After Symptom Onset
Evolution of Papillitis After Symptom Onset

A portable slitlamp analysis at the time of symptom onset (day 2 after admission) had revealed noticeable papillary edema (image not available). Papillary optical coherence tomography on postadmission days 30 (A and B) and 48 (C and D) showed that the right papillary edema had become very discrete on day 30 (A). Nevertheless, by day 48, the right ocular neuropathy had progressed to severe optic nerve atrophy (C). I indicates inferior; N, nasal; S, superior; T, temporal.

One and a half months after symptom onset, visual acuity remained +2 logMAR (hand movement) OD. A clear cornea and anterior chamber or vitreous inflammation regression were observed. A fundus examination showed severe papillary atrophy (Figure 2C).

Discussion

Cases of SARS-CoV-2 have been known to induce conjunctivitis1,2 and asymptomatic nonneuropathic retinal lesions,3 and the virus can be present in tears.4 Moreover, in animals, other coronaviruses can cause conjunctivitis, anterior uveitis, retinitis, and disc neuritis.2 However, the ability of SARS-CoV-2 to induce serious ocular disease has been unknown. To our knowledge, this is the first reported case of inflammatory ocular neuropathy that was associated with uveitis, may have been induced by SARS-CoV-2, and resulted in permanent loss of visual acuity.

It is notable that although initial disc edema was moderate to mild in this patient, it led to severe atrophy. Other viruses (eg, varicella-zoster virus) have also been reported to have this effect.5

While central nervous system involvement (eg, meningo-encephalitis) has been reported in patients infected with SARS-CoV-2,6 it could not explain these findings because cranial magnetic resonance imaging had clear results. While it remains possible these findings were idiopathic, the temporal association between SARS-CoV-2 infection and the ocular manifestations and the lack of relevant history support the possibility that SARS-CoV-2 caused the neuropathic ocular inflammation in this case.

Conclusions

This case suggests that COVID-19 manifestations may include isolated inflammatory optic neuritis that leads to permanent visual acuity loss. To limit the functional consequences of ocular neuropathy in patients infected by SARS-CoV-2, it should be diagnosed and treated early.

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Article Information

Corresponding Author: Jean Marc Perone, MD, Ophthalmology Department, Metz-Thionville Regional Hospital Center, Lorraine University, Mercy Hospital, 1 Allee du Chateau, CS 45001 57085 Metz-Cedex 03, France (jm.perone@chr-metz-thionville.fr).

Published Online: December 17, 2020. doi:10.1001/jamaophthalmol.2020.5695

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank Yinka Zevering, PhD, SciMeditor Medical Writing Services, for her assistance in preparing the manuscript. She was compensated for her contribution. We also thank the patient for granting permission to publish this information.

References
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Wu  P, Duan  F, Luo  C,  et al.  Characteristics of ocular findings of patients with coronavirus disease 2019 (COVID-19) in Hubei province, China.   JAMA Ophthalmol. 2020;138(5):575-578. doi:10.1001/jamaophthalmol.2020.1291PubMedGoogle ScholarCrossref
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Seah  I, Agrawal  R.  Can the coronavirus disease 2019 (COVID-19) affect the eyes? a review of coronaviruses and ocular implications in humans and animals.   Ocul Immunol Inflamm. 2020;28(3):391-395. doi:10.1080/09273948.2020.1738501PubMedGoogle ScholarCrossref
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Marinho  PM, Marcos  AAA, Romano  AC, Nascimento  H, Belfort  R  Jr.  Retinal findings in patients with COVID-19.   Lancet. 2020;395(10237):1610. doi:10.1016/S0140-6736(20)31014-XPubMedGoogle ScholarCrossref
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Xia  J, Tong  J, Liu  M, Shen  Y, Guo  D.  Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection.   J Med Virol. 2020;92(6):589-594. doi:10.1002/jmv.25725PubMedGoogle ScholarCrossref
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Kedar  S, Jayagopal  LN, Berger  JR.  Neurological and ophthalmological manifestations of varicella zoster virus.   J Neuroophthalmol. 2019;39(2):220-231. doi:10.1097/WNO.0000000000000721PubMedGoogle ScholarCrossref
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Moriguchi  T, Harii  N, Goto  J,  et al.  A first case of meningitis/encephalitis associated with SARS-coronavirus-2.   Int J Infect Dis. 2020;94:55-58. doi:10.1016/j.ijid.2020.03.062PubMedGoogle ScholarCrossref
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    1 Comment for this article
    EXPAND ALL
    Ophthalmic manifestations in a Post COVID Patient
    Srinivasan Sanjay, MS(Oph), DNB(Oph), MMed | Narayana Nethralaya, Bengaluru, India
    We congratulate Francois et al 1 for their excellent report. We have also reported a case of panuveitis with bilateral optic disc swelling and hyperemia with right central retinal artery occlusion in an Asian Indian male (Article in Press).
    We would like to know if Francois et al 1 had done an aqueous tap for their patient. Our patient’s aqueous tap for reverse transcriptase polymerase chain reaction (RT-PCR) was negative. We thereby postulated that in our patient it was immune mediated rather than the direct effect of the (severe acute respiratory syndrome Corona virus (SARS-CoV2) virus.

    It will be
    interesting to know whether Francois et al 1 are able to add the status of hyper coagulability factors in their patient. Our patient had elevated hypercoagulability markers like the D- Dimer, serum ferritin, glutathiamine, and deranged liver enzymes, which we postulate as the cause for the uveitis and vascular event and elevated ESR and CRP as an attribute to the panuveitis and optic neuritis. Vascular balance is affected in COVID-19 patients due to endothelial inflammation leading to vasoconstriction, ischaemia and a procoagulant state.2,3
    Arterial and venous thrombotic events are more commonly seen in more than 30% of COVID-19 patients.2,3 Additionally, thrombophilia screening in a patient with papillophlebitis in a COVID-19 patient has been described by Insausti-García A 4 et al may be useful in this case.
    Our patient was treated with low dose systemic immunosuppressants (methrotrexate 7.5mg) initially and subsequently in consultation with immunologist, as a corticosteroid sparing drug to control the inflammation, for hypercoagulability status he was treated with acenocoumarol (2mg), ecospirin and oral ecospirin 75 mg, pentoxyphyline 400mg and for three months.
    As a single observation, one cannot determine the precise benefits or risks of the treatment chosen for the patient.


    First and Corresponding author: Srinivasan Sanjay
    Co –authors:
    Padmamalini Mahendradas, Ankush Kawali, Rohit Shetty
    Narayana Nethralya




    References
    1. François J, Collery AS, Hayek G, Sot M, Zaidi M, Lhuillier L, Perone JM. Coronavirus Disease 2019-Associated Ocular Neuropathy With Panuveitis: A Case Report. JAMA Ophthalmol. 2020 Dec 17. doi: 10.1001/jamaophthalmol.2020.5695. Epub ahead of print
    2. Becker RC. COVID-19 update: Covid-19-associated coagulopathy. J Thromb Thrombolysis. 2020;50:54-67.
    3. Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020 Jul;191:145-147.
    4. Insausti-García A, Reche-Sainz JA, Ruiz-Arranz C, López Vázquez Á, Ferro-Osuna M. Papillophlebitis in a COVID-19 patient: Inflammation and hypercoagulable state [published online ahead of print, 2020 Jul 30]. Eur J Ophthalmol. 2020;1120672120947591. doi:10.1177/1120672120947591
    CONFLICT OF INTEREST: None Reported
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