The Implications of SARS-CoV-2 Infection in a Series of Neuro-Ophthalmological Manifestations—Case Series and Literature Review

“

TL;DR

This case series describes three patients with neuro-ophthalmic manifestations associated with SARS-CoV-2 infection or vaccination: bilateral orbital cellulitis, retrobulbar optic neuritis, and central retinal vein thrombosis. Two cases improved with treatment, but the patient with central vein thrombosis and underlying hereditary thrombophilia progressed to no light perception. Clinicians should be aware that neuro-ophthalmological complications can occur even without respiratory symptoms and require prompt multidisciplinary management.

Full summary

4,973 CHARS

**Background** The COVID-19 pandemic, caused by SARS-CoV-2, has been associated with a wide range of systemic manifestations, including neurological and ocular complications. Neurological manifestations are reported in 14–57% of hospitalized patients, and ocular manifestations occur in up to 30% of hospitalized patients. Neuro-ophthalmological presentations include optic neuritis, cranial neuropathies, orbital cellulitis, and vascular occlusions. These can arise from direct viral effects, immune-mediated mechanisms, or as adverse events following vaccination. This case series reports three patients with neuro-ophthalmic diseases occurring in the context of COVID-19 infection or immunization.

**Methods** Three patients presenting to the Ophthalmology Clinic of St. Spiridon Hospital in 2021 were included. All underwent comprehensive ophthalmic evaluation including visual acuity (VA), intraocular pressure (IOP), color sense, visual field (VF) testing, ocular motility examination, and brain imaging (CT or MRI). Blood tests and interdisciplinary consultations were performed as indicated. Informed consent was obtained from all patients.

**Key Results** Case 1: A 45-year-old male with no prior medical history presented with binocular diplopia, painful red eyes, and lacrimal hypersecretion of 4 days' duration in April 2021. VA was 0.4 cc in both eyes (BE), IOP was 24 mmHg right eye (RE) and 23 mmHg left eye (LE). Biomicroscopy showed conjunctival congestion, dilated episcleral vessels, and corneal epithelial edema 2+. Ocular motility showed slight limitation of abduction BE. He tested positive for SARS-CoV-2. Blood tests revealed leukocytosis with neutrophilia, thrombocytosis, elevated ESR and CRP. CT with contrast diagnosed bilateral orbital cellulitis with infiltrating appearance of intra- and extraconal fat, infiltration of bilateral malar and palpebral subcutaneous tissue, and discreet infiltrative appearance of the internal rectus muscles (RE 4.7 mm, LE 5.4 mm). No other etiology was identified. Treatment included Ceftriaxone (2 g/day), Vancomycin, Aerius, Moxifloxacin, Betabioptal, chloramphenicol, and Naabak. After 1 month, eye movements improved, periocular inflammation reduced, VF and OCT were normal, and VA improved.

Case 2: A 52-year-old female with prior SARS-CoV-2 infection 1 month before presentation in September 2021 complained of decreased VA in RE and positive central scotoma, preceded by photopsia and vertigo. VA was 1.0 RE and 1.2 LE, IOP normal, anterior segment normal, no RAPD, color sense and motility normal. Fundus examination showed optic nerve papilla with erased contour in the nasal sector. VF RE showed centrocecal scotoma. OCT macula and optic nerve were normal. Contrast-enhanced MRI was normal. Blood tests were normal. Diagnosis: retrobulbar optic neuritis RE, post-SARS-CoV-2 infection. Treatment: intravenous methylprednisolone 1 g/day for 3 days, then 1 mg/kg/day for 11 days. Gradual recovery of VF changes. At 3-month follow-up, OCT showed moderate thinning of retinal nerve fiber layers in superior and nasal sectors (superior RNFL 136 vs. 94 µm, nasal 66 vs. 48 µm) without affecting VA.

Case 3: A 55-year-old male with hypertension presented with sudden, painless decrease in VA RE approximately 3 weeks after first dose of Pfizer COVID-19 vaccine. VA RE was perception of light uncertain, VA LE 0.7 fc, 1 corrected, IOP normal. Fundus examination showed RE papillary edema, peripapillary flame hemorrhages, dilated veins. LE optic nerve normal. Blood tests showed mild hypercholesterolemia, inflammatory markers normal. Contrast-enhanced MRI showed right optic nerve 10 mm with moderate contrast uptake. Thrombophilic profile revealed factor XIII, homozygous mutant PAI gene, heterozygous mutant factor V, heterozygous mutant MTHFR C677T, MTHFR A1298C homozygous mutant, homocysteine >21.2 µmol/mL (normal <10). Hematology confirmed hereditary thrombophilia and hyperhomocysteinemia. Diagnosis: central retinal vein thrombosis RE in context of COVID-19 vaccination, with hereditary thrombophilia and hyperhomocysteinemia as aggravating factors. Treatment with methylprednisolone, pentoxifylline, ceftriaxone, enoxaparin sodium 0.4 × 2/day, acetylsalicylic acid 75 mg/day, and natalvit for 30 days. No favorable result; VA evolved to no light perception.

**Clinical Implications** Neuro-ophthalmological manifestations of SARS-CoV-2 infection or vaccination are rare but can occur even without respiratory symptoms. Early diagnosis and multidisciplinary management are crucial. In case 3, delayed presentation and underlying thrombophilia contributed to irreversible vision loss. Clinicians should consider thrombophilic screening in patients with vascular occlusions post-vaccination. The favorable outcomes in cases 1 and 2 highlight the importance of prompt treatment. Long-term follow-up is recommended to monitor for sequelae such as optic atrophy or development of multiple sclerosis.