Bilateral Optic Neuritis After Vero Cell-Derived Antirabies Vaccination

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Gour Wang, MD Bilateral Optic Neuritis After Vero Cell–Derived Antirabies Vaccination Jue Wang, MD, Mingxia Tian, MD, Fengjiao Li, MD, Xiangge Du, MD, Ying Han, MD, PhD, Ping Ma, MD, PhD A 23-year-old man presented with an 11-day history of diminished vision in both eyes with the left eye more affected. This was associated with headache and mild orbital pain but no eye pain with movement. The patient had a history of being bitten by a dog 25 days earlier and was administered subcutaneous injection of rabies vaccine prepared from cultured Vero cell on Day 0, 3, 7, and 14 after the dog bite. He became visually symptomatic on the second day after the fourth injection. Except for myopia, there was no history of any other ocular or neurologic diseases. Ocular examination revealed that the best-corrected visual acuity (BCVA) was 20 of 50 in the right eye and 20 of 100 in the left eye. Intraocular pressure was 18 mm Hg in the right eye and 21 mm Hg in the left eye by noncontact tonometry. Slit-lamp examination was normal in both eyes. There was no inflammation in the anterior chamber. Funduscopy using +90 D lens revealed bilateral optic disc hyperemia with edema and blurred margins. There was also retinal venous tortuosity with dilatation (Fig. 1). Optical coherence tomography revealed the optic disc was edematous in both eyes. Fundus fluorescein angiography demonstrated tortuosity of the retinal vessels with disc leakage suggestive of optic disc edema. Automated visual field 30-2 demonstrated generalized depression on the total deviation plot in both eyes. Dense superior arcuate Department of Ophthalmology (JW, MT, FL, XD, PM), Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China; Department of Ophthalmology (YH, PM), University of California, San Francisco, California; and Department of Ophthalmology (MT), The First People’s Hospital of Jining Affiliated to Jining Medical College, Jining, China. Supported by the Shandong Government sponsored study abroad program scholarship and the Scientific Research Foundation of Shandong Province of Outstanding Young Scientist Award (No. BS2010YY052). The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www. jneuro-ophthalmology.com). Address correspondence to Ping Ma, MD, PhD, Department of Ophthalmology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, #324 Jing5, Jinan, Shandong 250021, China; E-mail: [e-mail] e300 defect with possible inferior arcuate defect was shown in the right eye and likely inferior arcuate change with scattered superior defect in the left eye (Fig. 2). The flash visual electrophysiology showed normal latency but decreased amplitude in both eyes with 1.0 Hz. Otherwise, his general physical examinations were normal. Laboratory tests showed normal total blood count, biochemistry profile, erythrocyte sedimentation rate, Treponema pallidum hemagglutination test, and chest x-ray. Antibodies to aquaporin-4 (AQP4), myelin oligodendrocyte glycoprotein, and glial fibrillary acidic protein were negative. The T-Spot test for tuberculin T cells was negative. The MRI scan did not show obvious enhance along optic nerves or changes in the brain. The patient did not receive enhanced MRI and refused to have lumbar puncture for cerebrospinal fluid examination. We diagnosed the patient with bilateral optic neuritis related to antirabies vaccination. The patient was treated with 2 doses Methylprednisolone of intravenous drip (500 mg), reduced to 300 mg for 2 days and then changed into oral prednisolone (0.5 mg/kg). On the second day, the patient’s BCVA was improved. After 7-day treatment, the disc edema had reduced, and the BCVA had recovered to 20 of 20 in both eyes. One week later, his Humphrey visual field has significantly improved in both eyes (See Supplemental Digital Content, Supplement Fig. 1, http://links. lww.com/WNO/A436). Three months later, the patient has fully recovered with normal BCVA and fundus examination. Rabies is still a public health concern in developing countries, especially in Asia and Africa. There is no efficient treatment against rabies. Human rabies prevention relies largely on vaccination. Neurologic complications after antirabies vaccination are rare, and complication of optic nerve complications is extremely rare. A few cases of optic neuritis have been reported after antirabies vaccination either from the sheep brain or chick embryo (1–5). The onset of symptoms usually occurs 1–3 weeks to as much as 100 days after vaccination. The mechanism is believed to immune complex– mediated vascular injury with subsequent blood–brain barrier impairment, which leads to inflammation and Wang et al: J Neuro-Ophthalmol 2021; 41: e300-e302 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. Funduscopic photographs at presentation showing optic disc hyperemia with edema and blurred margins, and retinal venous tortuosity with dilatation. demyelination. This also might be responsible for our case, although we are not sure about it. Nowadays cell cultured vaccines have replaced nerve tissue vaccines in China and are recommended by WHO, which is considered to be safe and well tolerated. The side effects were mainly local reactions, including pain at the injection site, swelling, sclerosis, itching, edema, and lymphadenopathy. Because the vaccine is purified with very few albumins, the systemic side effects of vaccination are very rare. This is the first report of optic neuritis developed after adjuvant-free Vero cell–derived rabies vaccination. This complication has not been included in manufacturer’s information. It is reported that this type of complications generally recovers rapidly and completely after treatment with corticosteroids. Bilateral optic neuritis in this patient FIG. 2. Automated visual field 30-2 demonstrated generalized depression on the total deviation plot in both eyes. Dense superior arcuate defect with possible inferior arcuate defect were present in the right eye. There was a likely inferior arcuate change with scattered superior defects in the left eye. Wang et al: J Neuro-Ophthalmol 2021; 41: e300-e302 e301 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence followed the same trend and improved quickly in 2 days and regained normal vision in both eyes finally. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: P. Ma; b. Acquisition of data: F. Li and X. Du; c. Analysis and interpretation of data: J. Wang and M. Tian. Category 2: a. Drafting the manuscript: J. Wang and Y. Han; b. Revising it for intellectual content: Y. Han and P. Ma. Category 3: a. Final approval of the completed manuscript: P. Ma. e302 REFERENCES 1. Cormack HS, Anderson LAP. Bilateral papillitis following antirabies inoculation recovery. Br J Ophthalmol. 1934;18:167–168. 2. Consul BN, Purohit GK, Chabra HN. Antirabies vaccine optic neuritis. Indian Med Sci. 1968;22:630–632. 3. Gupta V, Bandyopadhyay S, Bapuraj JR, Gupta A. Bilateral optic neuritis complicating rabies vaccination. Retina. 2004;24:179–181. 4. Saxena R, Sethi HS, Rai HK, Menon V. Bilateral neuro-retinitis following chick embryo cell anti-rabies vaccination-a case report. BMC Ophthalmol. 2005;17:20. 5. Agarwal A, Garg D, Goyal V, Pandit AK, Srivastava AK, Srivastava MP. Optic neuritis following anti-rabies vaccine. Trop Doct. 2019;50:85–86. Wang et al: J Neuro-Ophthalmol 2021; 41: e300-e302 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.