Authors: Jossy, Ajax; Jacob, Ninan; Sarkar, Sandip; Gokhale, Tanmay; Kaliaperumal, Subashini; Deb, Amit K IJO Ophthalmology

Abstract

Neuroophthalmic manifestations are very rare in corona virus disease-19 (COVID-19) infection. Only few reports have been published till date describing COVID-19-associated neuroophthalmic manifestations. We, hereby, present a series of three cases who developed optic neuritis during the recovery period from COVID-19 infection. Among the three patients, demyelinating lesions were identified in two cases, while another case was associated with serum antibodies against myelin oligodendrocyte glycoprotein. All three patients received intravenous methylprednisolone followed by oral steroids according to the Optic Neuritis Treatment Trail ptotocol. Vision recovery was noted in all three patients, which was maintained at 2 months of the last follow up visit.

COVID-19 infection predo minantly causes a respiratory illness, but it can have a myriad of symptoms, affecting almost all organs of the body.[¹] Varied ocular manifestations including conjunctivitis, episcleritis, vascular occlusions, dacryoadenitis, mucormycosis, etc., have been reported in COVID-19 infection.[²] Neuroophthalmic manifestations in COVID-19 infection are uncommon, but they can seldom develop either during the active course or the recovery period.[³] Neuroophthalmic manifestations of COVID-19 infection includes optic neuritis, acute transverse myelitis, viral encephalitis, toxic encephalopathy, leukoencephalopathy, acute disseminated encephalomyelitis, diffuse corticospinal tract signs, etc.[⁴] Only a handful reports of optic neuritis associated with COVID-19 infection with or without demyelinating lesions have been published. Few of them are associated with serum antibodies against myelin oligodendrocyte glycoprotein (MOG).[^{567891011121314151617181920}] In this report, we describe the clinical profile and treatment outcome of three patients who developed optic neuritis during recovery from COVID-19 infection.

Case Reports

Case 1

A 16-year-old boy presented with sudden gross diminution of vision in the left eye (LE) for 3 days with headache and eyepain on extraocular movements. His past history was unremarkable. The patient had tested positive for COVID-19 infection with reverse transcription polymerase chain reaction (RT-PCR) 2 weeks prior to the incident. He was advised home isolation without any supplemental oxygen or steroids. Systemic and neurological examinations were unremarkable. On ocular examination, best-corrected visual acuity (BCVA) was 20/20 in the right eye (RE) and perception of light (PL+) in the LE, with a grade 2 relative afferent pupillary defect in the LE. Fundus examination revealed normal optic discs in both eyes with no evidence of disc edema or hyperemia [Fig. 1a and 1b]. A diagnosis of LE retrobulbar neuritis was made. Laboratory investigations, imaging, treatment received, and disease course are provided in Table 1.

Case 2

A 35-year-old male presented with sudden vision loss in LE with pain on extraocular movements for 1 week. His past history was unremarkable. He was tested positive for COVID-19 infection with RT-PCR 6 months prior to the vision loss. He was advised home isolation and did not require oxygen or steroids for COVID-19. On ocular examination, BCVA was 20/20 in RE and 20/600 in LE, with grade I RAPD in LE. Fundus examination of the LE revealed edematous disc with blurred margins and peripapillary edema, which was confirmed on optical coherence tomography, while the RE fundus was normal [Fig. 2a and 2b]. A diagnosis of LE papillitis was made. Laboratory investigations, imaging, treatment, and disease course are described in Table 1.

Case 3

A 38-year-old male presented with sudden gross diminution of vision and pain on extraocular movements in the LE for 5 days. The patient had a similar complaint in the LE 1 month ago. He was treated elsewhere for the same with intravenous methylprednisolone and oral prednisolone. There was symptomatic improvement in the vision within a week following the initiation of treatment. However, he noticed another similar episode of decreased vision in the LE 3 weeks later, when he presented to us. He was tested positive for COVID-19 infection with RT-PCR one-and-half month prior to the current episode. He was advised home isolation, and he also did not require oxygen or steroids for COVID-19 infection. Systemic examination was unremarkable. On ocular examination, BCVA was RE 20/20 and LE hand movements (HM+), with grade III RAPD in the LE. Fundus examination showed normal discs in both eyes [Fig. 3a and 3b]. A diagnosis of LE retrobulbar neuritis was made. Laboratory investigations, imaging findings, treatment, and disease course are described in Table 1.

Discussion

Optic neuritis is an inflammatory demyelinating optic neuropathy causing acute uniocular or binocular loss of vision.[²¹] Optic neuritis is mainly a clinical diagnosis based on history and examination findings. Investigations like magnetic resonance imaging, lumbar puncture, and antibodies against AQP4 and MOG help in finding the association and cause of vision loss.[²¹] Once the diagnosis is established, treatment is done based on optic neuritis treatment trial (ONTT) protocol.[²²]

Neurotropism of the virus was postulated as one of the mechanisms for neuroophthalmic manifestations.[²] Another mechanism involves molecular mimicry where the viral antigens trigger host immune response directed toward the CNS myelin proteins.[⁴⁶] All the three cases reported by us had viral prodromes and positive COVID-19 infection. It is interesting to note that all three cases had mild COVID-19 infections with no oxygen requirement or steroid use, and their recoveries were uneventful. Vision loss in all the three cases happened during the recovery period of the infections and dramatic response to steroids points toward an inflammatory disorder triggered by the viral antigen. In the third case, the patient had two similar episodes of vision loss in 2 months after the COVID-19 infection. He was tested positive for MOG antibody. MOG antibody-associated optic neuritis usually has good visual recovery with good response to steroids but shows bilaterality and recurrence. Our case also showed initial good response to systemic steroids with recurrence within 2 weeks of discontinuation of steroids. MOG antibody-associated optic neuritis in COVID-19 infection has been reported by Zhou et al.,[⁶] Zoric et al.,[¹⁰] Kugure et al.,[¹²] Sawalha et al.,[⁵] de Ruijter et al.,[¹⁴] Rojas-Correa et al.[¹⁹]. Table 2 describes the details of all cases of COVID-19-associated optic neuritis. Due to the ongoing COVID-19 pandemic, we can expect more similar cases in future. So, prospective studies are warranted to establish the relationship between the viral antigen, severity of COVID-19 infection, and associated optic neuritis.

Conclusion

Neuro-ophthalmic manifestations are rare in COVID-19 infection, and can be seen either during the active disease phase or the recovery phase.[³] Optic neuritis is one such rare manifestation. The three cases of optic neuritis being reported by us had mild COVID-19 infection. Two cases developed ocular symptoms and signs within the first six weeks of recovery while another case developed ocular manifestations six months after recovery from COVID-19. All the three cases showed good response to systemic steroids with significant visual recovery. Keeping the ongoing pandemic in perspective, we should, therefore, be vigilant in identifying the neuro-ophthalmic features of COVID-19 infection to prevent irreversible vision loss.