Neuro-Ophthalmological Complications of the COVID-19 Vaccines: A Systematic Review

Background: A worldwide mass vaccination campaign against the coronavirus disease 2019 (COVID-19) pandemic is currently underway. Although the safety data of the clinical trials did not report specific concerns regarding neuro-ophthalmological adverse events, they involved a limited number of individuals and were conducted over a relatively short time. The aim of the current review is to summarize the available postmarketing data regarding the occurrence of neuro-ophthalmological and other ocular complications of the COVID-19 vaccines. Evidence acquisition: Electronic searches for published literature were conducted using Ovid MEDLINE, Embase, Web of Science, Google Scholar, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov. The search strategy incorporated controlled vocabulary and free-text synonyms for the concepts of COVID, vaccines, and visual and neuro-ophthalmologic diseases and symptoms. Results: A total of 14 case reports and 2 case series have been selected for inclusion in the final report, reporting 76 cases of post-COVID-vaccination adverse events. The most common adverse event was optic neuritis (n = 61), followed by uveitis (n = 3), herpes zoster ophthalmicus (n = 2), acute macular neuroretinopathy (n = 2), optic disc edema as an atypical presentation of Guillain-Barré syndrome (n = 1), (arteritic anterior ischemic optic neuropathy; n = 1), abducens nerve palsy (n = 1), oculomotor nerve palsy (n = 1), Tolosa-Hunt syndrome (n = 1), central serous retinopathy (n = 1), acute zonal occult outer retinopathy (n = 1), and bilateral choroiditis (n = 1). Most cases were treated with high-dose steroids and had a favorable clinical outcome. Conclusion: Since the implementation of the COVID-19 vaccination campaign in the past year, several post-COVID-vaccination neuro-ophthalmological complications have been described. However, considering the number of individuals that have been exposed to the vaccines, the risk seems very low, and the clinical outcome in most cases is favorable. Therefore, on a population level, the benefits of the vaccines far outweigh the risk of neuro-ophthalmological complications.

Disease of the Year 2021 Encore: COVID-19 Section Editors: Bart Chwalisz, MD Marc J. Dinkin, MD Neuro-Ophthalmological Complications of the COVID-19 Vaccines: A Systematic Review Itay Lotan, MD, Melissa Lydston, Michael Levy, MD, PhD Background: A worldwide mass vaccination campaign against the coronavirus disease 2019 (COVID-19) pandemic is currently underway. Although the safety data of the clinical trials did not report specific concerns regarding neuro-ophthalmological adverse events, they involved a limited number of individuals and were conducted over a relatively short time. The aim of the current review is to summarize the available postmarketing data regarding the occurrence of neuro-ophthalmological and other ocular complications of the COVID-19 vaccines. Evidence Acquisition: Electronic searches for published literature were conducted using Ovid MEDLINE, Embase, Web of Science, Google Scholar, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov. The search strategy incorporated controlled vocabulary and free-text synonyms for the concepts of COVID, vaccines, and visual and neuroophthalmologic diseases and symptoms. Results: A total of 14 case reports and 2 case series have been selected for inclusion in the final report, reporting 76 cases of post-COVID-vaccination adverse events. The most common adverse event was optic neuritis (n = 61), followed by uveitis (n = 3), herpes zoster ophthalmicus (n = 2), acute macular neuroretinopathy (n = 2), optic disc edema as an atypical presentation of Guillain–Barré syndrome (n = 1), (arteritic anterior ischemic optic neuropathy; n = 1), abducens nerve palsy (n = 1), oculomotor nerve palsy (n = 1), Tolosa–Hunt syndrome (n = 1), central serous retinopathy (n = 1), acute zonal occult outer retinopathy (n = 1), and bilateral choroiditis (n = 1). Most cases were treated with high-dose steroids and had a favorable clinical outcome. Department of Neurology (IL, ML), Division of Neuroimmunology and Neuroinfectious Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; and Treadwell Virtual Library for the Massachusetts General Hospital (ML), Boston, Massachusetts. 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 full text and PDF versions of this article on the journal’s Web site (www. jneuro-ophthalmology.com). Address correspondence to Itay Lotan, MD, Department of Neurology, Division of Neuroimmunology and Neuroinfectious Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; E-mail: [e-mail] 154 Conclusion: Since the implementation of the COVID-19 vaccination campaign in the past year, several post-COVIDvaccination neuro-ophthalmological complications have been described. However, considering the number of individuals that have been exposed to the vaccines, the risk seems very low, and the clinical outcome in most cases is favorable. Therefore, on a population level, the benefits of the vaccines far outweigh the risk of neuro-ophthalmological complications. Journal of Neuro-Ophthalmology 2022;42:154–162 doi: 10.1097/WNO.0000000000001537 © 2022 by North American Neuro-Ophthalmology Society T he development of vaccines and their implication in global health strategies to protect the population from infectious diseases is among the greatest accomplishments of modern medicine. Following the emergence of the Coronavirus disease 2019 (COVID-19) pandemic, several vaccines were rapidly developed and gained approval from the regulatory authorities for emergence use. As of September 24, 2021, 7 vaccines have been officially approved by the world health organization. The Pfizer–BioNTech (BNT162b2) and Moderna (mRNA-1273) are messenger-RNA (mRNA) vaccines that introduce the genetic material of the spike glycoprotein of severe acute respiratory syndromeassociated coronavirus-2 (SARS-CoV-2) to human cells; the AstraZeneca (AZD1222, ChAdOx1 nCoV-19, Vaxzevria), Janssen (Johnson & Johnson, Ad26.COV2.S), and Covishield (AstraZeneca formulation) vaccines use a nonreplicating viral vector to present the SARS-COV-2 genes/ antigens to the target host, and the Sinovac (CoronaVac) and Sinopharm (BBIBP-CorV) vaccines use inactivated virus (1–4). Based on prior experience with other vaccines, postvaccination neuro-ophthalmological adverse events are considered rare. These include mainly postvaccination optic neuritis (ON) (5–8). In addition, extraocular nerve palsies and other intra-ocular inflammatory conditions have been reported, including orbital myositis, uveitis, and chorioretinal syndromes (7,9–11). The etiology of these complications, as Lotan et al: J Neuro-Ophthalmol 2022; 42: 154-162 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Disease of the Year 2021 Encore: COVID-19 well as of other vaccine-mediated organ-specific complications, is presumably immune-mediated (6,12,13). The Safety data from the phase 3 trials of the COVID19 vaccines have not reported neuro-ophthalmological complications (14–18). However, these trials involve a relatively small proportion of the population (usually tens of thousands of persons in each trial) and are conducted over a relatively short time. Therefore, some side effects may not be documented in phase 3 trials and may only become evident in the postmarketing period. In this review, we aim to summarize the currently available data on neuro-ophthalmological and other ocular complications of the COVID vaccines. METHODS This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic searches for published literature were performed by a medical librarian using Ovid MEDLINE (1946 to present), Embase.com (1947 to present), Web of Science (1900 to present), Google Scholar (no coverage listed) using Publish or Perish software (19), Cochrane Central Register of Controlled Trials via Ovid (1991 to present), Cochrane Database of Systematic Reviews via Ovid (2005 to January 28, 2021), and ClinicalTrials.gov (1999 to present). The searches were run in September 2021. The search strategy incorporated controlled vocabulary and free-text synonyms for the concepts of COVID, vaccines, and visual and neuro-ophthalmologic diseases and symptoms. For the concept of COVID-19, a hedge created by Ket et al was used (20). The full database search strategies are documented in Supplemental Digital Content 1 (see Appendix 1, http://links.lww.com/WNO/ A563). No restrictions on language or methodology were applied. A date range (2019–2021) was applied for the COVID concept. All identified studies were combined in a single reference manager (EndNote) and deduplicated using both EndNote and the Systematic Review Assistant-Deduplication Module (21). The citations were then uploaded into Covidence systematic review software. All papers reporting any neuro-ophthalmological or ocular complication following any of the COVID-19 vaccines currently in use have been selected. Figure 1 illustrates a PRISMA flow chart of the papersselection process for this review. RESULTS A total of 14 case reports and 2 case series have been selected for inclusion in the final report. Overall, 76 cases of post-COVID-vaccination adverse events have been reported, including ON (n = 61) (22–25), optic disc edema as atypical presentation of Guillain–Barre syndrome (n = 1 Lotan et al: J Neuro-Ophthalmol 2022; 42: 154-162 FIG. 1. Flow chart of paper selection process. (26), arteritic anterior ischemic optic neuropathy (AAION; n = 1) (27), abducens nerve palsy (n = 1) (28), oculomotor nerve palsy (n = 1) (29), Tolosa–Hunt syndrome (n = 1) (30), herpes zoster ophtalmicus (n = 2) (31), uveitis (n = 3) (32–34), acute macular neuroretinopathy (n = 2) (35), central serous retinopathy (n = 1) (36), acute zonal occult outer retinopathy (AZOOR; n = 1) (27), and bilateral choroiditis (n = 1) (37). Optic Neuritis/Perineuritis A series of 4 cases of ON, one case report of bilateral ON and thyroiditis, and one case of optic perineuritis have been described (23–25). In addition, a preprint describing a series of 55 ON cases has been identified (22). Kaulen et al reported 4 cases of ON in a broader (overall 21 cases) prospective case study of neurological autoimmune complications in temporal association with the COVID-19 vaccines. All ON cases occurred among 155 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Disease of the Year 2021 Encore: COVID-19 recipients of the Pfizer-BioNTech vaccine and demonstrated contrast enhancement of the affected optic nerve on MRI. Treatment consisted of intravenous methylprednisolone (IVMP, n = 4) and plasma exchange (PLEX, n = 1 (25)). Martinez–Alvarez et al describe 55 cases of ON, collected from specialized neuro-ophthalmology and neurology centers in 10 different countries. Of these, 37 (67.3%) were women, and the median age was 45 (range 18–75). Thirtyeight patients (69.1%) received the AstraZeneca vaccine, 13 (23.6%) received the Pfizer vaccine, and 4 (7.3%) received the Sinovac vaccine. Most cases of ON occurred within 3 weeks from vaccination (range 1–69 days). Forty-seven patients (85.4%) had no prior history of demyelinating disease. Myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) antibody testing results were available for 36 patients, whereas for the remaining 19, the results are pending. Fourteen patients in the series (25.4% of the whole series, but 38.9% of those with available antibody results) were positive for MOG-Immunoglobulin (IgG), whereas none were positive for AQP4-IgG. Optic disc swelling on funduscopic examination was present in 27 cases (49.1%). Treatment consisted of high-dose corticosteroids, administered intravenously in 40 cases, and by mouth in 8 cases (the remaining 7 cases were not treated with steroids). PLEX was administered in 6 cases (not reported whether in conjunction with steroids or as a sole treatment). The visual outcome was overall good (median logMAR 0.0), but poor for some individuals (MAX logMAR 3.0; the number of cases not reported) (22). Leber et al reported a case of bilateral ON in a 32-yearold woman, presenting 12 hours after the second dose of the CoronaVac vaccine. Of note, fundus examination revealed bilateral disc swelling, and the patient was found to have positive anti-MOG antibodies, detected at 1:320 titer by a cell-based assay. In addition, a general serologic workup revealed high levels of thyroid-stimulating hormone, antithyroglobulin, and antithyroid peroxidase, compatible with subacute thyroiditis. Treatment with high-dose IVMP followed by an oral steroid regimen resulted in rapid improvement of visual acuity and pain and improvement of optic disc swelling (23). Takenaka et al reported a case of optic perineuritis in a 75-year-old woman. The onset of symptoms was noted 4 days after the first dose of the Pfizer-BioNTech vaccine. Interestingly, during the workup, the patient was found to have positive myeloperoxidase antineutrophil cytoplasmic antibodies. Treatment with high-dose IVMP resulted in rapid clinical improvement (24). Other Optic Nerve Disorders Two cases of postvaccination herpes zoster ophthalmicus have been described by Thimmanagari et al. In one case, a 42-year-old man developed characteristic skin lesions 156 associated with restricted ocular movements and reduced visual acuity one week postvaccination; in the second case, a 49-year-old man developed erythematous papules and vesicles on the right side of the forehead (i.e., V1 dermatome) and edema of the right upper eyelid, without signs of extraocular or optic nerve involvement. Both patients were treated with systemic antiviral medications with a good clinical outcome (31). Introna et al reported bilateral swollen disc as an atypical clinical presentation of post-COVID-vaccination Guillain– Barré syndrome (GBS). The patient, a 62-year-old man, presented 10 days after the first dose of the AstraZeneca vaccine with visual discomfort and was found to have severe bilateral optic disc edema on funduscopic examination. Three days later, the patient developed typical GBS symptoms, consisting of ascending tetraparesis, bilateral facial weakness, dysphagia, urinary retention, and distal paresthesia (26). Maleki et al reported a case of AAION in a 79-year-old woman. The patient suffered bilateral visual loss 2 days after receiving the second dose of the Pfizer vaccine. High erythrocyte sedimentation rate and C-reactive protein levels were noted, and a right temporal artery biopsy was compatible with AAION. The patient was treated with high-dose IVMP for 3 days, followed by 60 mg of oral prednisone with a slow taper and weekly subcutaneous tocilizumab. The clinical outcome was not reported (27). Extraocular Eye Movement Complications Reyes-capo et al reported a case of abducens nerve palsy in a 59-year-old woman. The symptoms developed 2 days after vaccination with the Pfizer-BioNTech Vaccine (first or second dose not reported) and were unchanged at the last follow-up (treatment and duration of symptoms not reported) (28). Pappaterra et al reported a case of oculomotor nerve palsy in an 81-year-old woman. The symptoms developed one day after the first dose of the Moderna vaccine and improved spontaneously to near-complete resolution after 11 days (29). Chuang et al reported a case of Tolosa–Hunt syndrome in a 45-year-old man presenting 4 days after vaccination with the Moderna vaccine (first or second dose not reported). The patient was treated with IVMP followed by oral steroids regimen, with an early improvement of pain and improvement of cranial nerve deficit after 2 months (30). Uveitis Two cases of anterior uveitis and one case of panuveitis have been reported (32–34). ElSheikh et al reported a case of bilateral anterior uveitis in an 18-year-old woman, presenting 5 days after the second dose of the Sinopharm vaccine. Treatment with topical steroids resulted in clinical Lotan et al: J Neuro-Ophthalmol 2022; 42: 154-162 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Disease of the Year 2021 Encore: COVID-19 improvement within 1 week and complete clinical resolution after 6 weeks (32). Renisi et al reported a case of anterior uveitis in a 23-year-old man. The symptoms occurred 14 days after the second dose of the PfizerBioNTech and resolved within 6 weeks after treatment with dexamethasone and topical cycloplegic eye drops (34). Mudie et al reported a case of bilateral panuveitis in a 43-yearold woman, presenting 3 days after the second dose of the Pfizer-BioNTech vaccine. A clinical resolution was noted after 3 weeks of treatment with high-dose oral steroids. However, after 3 weeks of steroid taper, a clinical recurrence was observed. The patient restarted oral prednisone and is now planned for an extended taper regimen (33). Other Maleki et al reported a case of bilateral AZOOR in a 33year-old woman, presenting 10 days after the second dose of the Moderna vaccine. The patient was treated with an intravitreal dexamethasone implant. The outcome was not reported (27). Goyal et al reported a case of bilateral choroiditis in a 34year-old man. The symptoms presented 4 days after the second dose of the Covishield vaccine and improved after 11 days of high-dose oral prednisone treatment (37). Fowler et al reported a case of central serous retinopathy in a 33-year-old man presenting 3 days after vaccination with the Pfizer-BioNTech vaccine (first or second dose not reported). The patient was treated with spironolactone, with complete resolution of symptoms after 3 months (36). Mambretti et al reported 2 cases of acute macular neuroretinopathy in 22-year-old and 28-year-old women. Both cases presented 2 days after the first dose of the AstraZeneca vaccine. The treatment and outcome of both cases have not been reported (35). CONCLUSIONS The implementation of vaccination strategies is a key tool for preventing the spread of infectious diseases. Although the use of many vaccines is considered safe, occasional adverse events, including induction or reactivation of autoimmune diseases, have been reported (38,39). The currently available data regarding neuroophthalmological adverse events of the COVID vaccines consist of a limited number of case reports and a series of 55 cases (only available as a preprint). Therefore, it is not possible to estimate the incidence of these events. However, considering the large number of individuals that have so far been exposed to the COVID vaccines and the small number of publications, the occurrence of neuro-ophthalmological (and other ocular) complications seems very rare on a population level. A temporal association with the vaccine should be demonstrated for an event to be considered vaccinerelated. In this regard, the latency time reported for the Lotan et al: J Neuro-Ophthalmol 2022; 42: 154-162 post-COVID-vaccination ocular adverse events is consistent with the time reported in the literature for other vaccines (5,6,9). However, it should be noted that individual case reports of an event that occurs shortly after vaccination may still be coincidental. Therefore, convincing evidence for a causative role of a vaccine requires large case–control epidemiological studies. Another factor that supports the possible causative role of vaccination is that, in most cases, no other cause was identified. In 9 cases of post-COVID-vaccination ocular adverse events (8 ON and 1 uveitis), an underlying immune-mediated disease that may have been exacerbated by the vaccine has been identified (Table 1) (22,32). In another 2 cases of ON, an antibody known to cause ON has been recognized for the first time after vaccination (Table 1) (23,24). Because the antibody status before immunization was unknown, it is not possible to know whether the vaccine triggered the antibody production or if it was a trigger for the clinical presentation of a preexisting subclinical disease. Various mechanisms involved in triggering postvaccination autoimmune response have been postulated. These include cytokine production, expression of human histocompatibility leukocyte antigens, modification of surface antigens, induction of novel antigens, molecular mimicry, bystander activation, epitope spreading, polyclonal activation of B cells, and an immune reaction to vaccination adjuvants (38,40–43). Considering the fact that acute immune-mediated events are often steroid-responsive, most postvaccination neuro-ophthalmological events have been treated with corticosteroids. The good outcome of many of these events is considered another supportive evidence for their immune-mediated nature. ON is the most common postvaccination neuroophthalmological complication reported in the literature (5,6). It should be noted that a significant proportion of the reported cases of ON that developed in temporal association with the COVID-vaccines was associated with MOG antibodies (22,23). Interestingly, presumed postimmunization ON attributed to other vaccines was predominantly anterior and bilateral (44–51). In some cases, a neuromyelitis opticalike (i.e., combined ON and myelitis) and acute demyelinating encephalomyelitis-like presentations were described (5,52–56). Of note, in some of these cases, the AQP4 antibodies were negative or not available (53–56). Although MOG-IgG was not tested in these cases, these clinical presentations are highly characteristic of MOG antibody disease (57–63). Therefore, it is possible that similarly to the described cases of ON presenting after the COVID vaccination (22,23), at least some can retrospectively be attributed to MOG-IgG. Several neurological vascular complications with potential neuro-ophthalmologic manifestations have been reported in temporal association to the COVID-19 vaccines. For example, cases of cerebral venous sinus 157 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Author (Reference #) Type of Complication Martinez-Alvarez et al. (22) Optic neuritis Leber et al. (23) Takenaka et al. (24) Kaulen et al. (25) Introna et al. (26) Optic neuritis Optic perineuritis Optic neuritis* Bilateral optic disc edema and visual discomfort (atypical presentation of GBS) Arteritic anterior ischemic optic neuropathy (AAION); bilateral acute zonal occult outer retinopathy (AZOOR) Abducens nerve palsy Oculomotor nerve palsy Tolosa–Hunt syndrome Herpes zoster ophthalmicus Maleki et al. (27) Reyes-capo et al. (28) Pappaterra et al. (29) Chuang et al. (30) Thimmanagari et al. (31) ElSheikh et al. (32) Mudie et al. (33) Renisi et al. (34) Mambretti et al. (35) Fowler et al. (36) Goyal et al. (37) Lotan et al: J Neuro-Ophthalmol 2022; 42: 154-162 Author (Reference #) Bilateral anterior uveitis Bilateral panuveitis Anterior uveitis Acute macular neuroretinopathy Central serous retinopathy Bilateral choroiditis Ethnicity Comorbidities Type of Vaccine Number of Patients Gender 55 1 1 4 1 37 females, 18 males Female Female NA* Male 32 75 Median age = 50 (range 22–86)* 62 Pfizer-BioNTech; Moderna 2 Females 79, 33 Pfizer-BioNTech Moderna Moderna Johnson and Johnson; Moderna Sinopharm Pfizer-BioNTech Pfizer-BioNTech AstraZeneca 1 1 1 2 Female Male Male Males 59 81 45 42, 49 1 1 1 2 Female Female Male Female 18 43 23 22, 28 Pfizer-BioNTech Covishield 1 1 Male Male 33 34 AstraZeneca (n = 38); Pfizer (n = 13; Sinovac,(n = 4) CoronaVac Pfizer-BioNTech Pfizer-BioNTech AstraZeneca Time from Vaccination to Clinical Onset Treatment MartinezAlvarez et al. (22) Caucasian ANA-positive juvenile idiopathic arthritis Median 18 days (range 1–69) IVMP (n = 40); oral steroids (n = 8); PLEX (n = 6) Leber et al. (23) NA None 12 hours after the second dose One gram of IVMP for 5 days followed by an oral steroid regimen Takenaka et al. (24) Caucasian Oral contraceptives Four days after the first dose of Pfizer High-dose IVMP Age Median age = 45 (range 18–75) Outcome Overall good visual outcome (median logMAR 0.0), but poor for some individuals (MAX logMAR 3.0; number of cases not reported) Rapid improvement of visual acuity and pain; improvement of disc swelling on after 20 days Rapid improvement Disease of the Year 2021 Encore: COVID-19 158 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. TABLE 1. Summary of neuro-ophthalmological and ocular adverse events following COVID-19 vaccination Lotan et al: J Neuro-Ophthalmol 2022; 42: 154-162 Author (Reference #) Ethnicity Comorbidities Time from Vaccination to Clinical Onset Treatment Outcome Kaulen et al. (25) Introna et al. (26) NA* NA* Median 11 days (range 3–23)* IVMP (n = 4); PLEX (n = 1) NA* Hispanic None Ten days after the first dose IVIG Maleki et al. (27) NA None Patient 1–2 days after the second dose of Pfizer; Patient 2–10 days after the second dose of Moderna Reyes-capo et al. (28) Pappaterra et al. (29) Chuang et al. (30) Caucasian HTN NA Hispanic No history of autoimmune disease None Two days after vaccination (not reported after which dose) One day after the first dose Patient 1- high dose IVMP pulse therapy (1 g) for 3 days followed by 60 mg of oral prednisone with a slow taper, plus weekly subcutaneous tocilizumab; Patient 2- intravitreal dexamethasone implant Not reported Motor, sensory and autonomic symptoms slowly improved; the outcome of optic disc swelling not reported Not reported Thimmanagari et al. (31) NA None ElSheikh et al. (32) NA DM-II, hyperlipidemia Mudie et al. (33) NA Renisi et al. (34) Mambretti et al. (35) NA Asthma; bipolar disorder, schizophrenia, and hyperlipidemia None NA HTN, hypercholester olemia, DM Four days after vaccination (not reported after which dose) One week after J&J; one week after the first dose of Moderna Five days after the second dose None One gram of IVMP for 3 days followed by an oral steroid regimen Systemic antiviral and antiviral eye drops Topical steroids Three days after the second dose Difluprednate drops plus oral prednisone 14 days after the second dose of Pfizer Two days after the first dose Dexamethasone and topical cycloplegic eye drops Not reported Unchanged at most recent follow-up Spontaneous near-total resolution after 11 days Early improvement of pain; improvement of cranial nerve deficit after 2 months Improved Clinical improvement within 1 week; complete resolution after 6 weeks Clinical resolution after 3 weeks of high dose steroids; recurrence after 3 weeks of steroid taper Clinical resolution after 6 weeks Not reported Disease of the Year 2021 Encore: COVID-19 159 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. (Continued ) 160 Goyal et al. (37) *This paper report 21 cases of neurological autoimmune complications occurring in temporal association to the COVID-19 vaccines. The demographic characteristics of all the included patients are reported together, and the specific data on the ON cases is not available. ANA, antinuclear antibody; DM, diabetes mellitus; GBS, Guillain–Barre syndrome; HTN, hypertension; IVIG, intravenous immunoglobulins; IVMP, intravenous methylprednisolone; OCT, optical coherence tomography; PLEX, plasma exchange. Significant improvement after 11 days Oral prednisone 1 mg\kg, tapered by 10 mg every week None Four days after the second dose Complete resolution at 3 months Spironolactone Three days after vaccination (not reported after which dose) Ten patients (18.2%) had a past medical history of autoimmune disease Caucasian (n = 44); Asian (n = 4); Hispanic (n=3); African (n = 2) Caucasian Fowler et al. (36) Author (Reference #) (Continued ) Ethnicity Comorbidities Time from Vaccination to Clinical Onset Treatment Outcome Disease of the Year 2021 Encore: COVID-19 thrombosis have been described following vaccination with the Janssen (J&J) vaccine (64). However, the neuroophthalmic findings of these cases have not been wellcharacterized. Other vascular complications, such as ischemic cerebrovascular accident and posterior reversible encephalopathy syndrome may occur in the postvaccination period, but would be of unclear relationship to the immunologic stimulus. In conclusion, since the implementation of the COVIDvaccination campaign in the past year, several post-COVIDvaccination neuro-ophthalmological and ocular complications have been described. However, based on the current data, the risk seems very low, and the clinical outcome in most cases is favorable. 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