COVID-19 Vaccine-Associated Optic Neuropathy: A Systematic Review of 45 Patients
Abstract
:1. Introduction
2. Materials and Methods
Data Extraction and Statistical Analysis
3. Results
3.1. Studies and Patients
3.2. Demographic Data
3.3. Visual Acuity Outcomes
Author | Article Type | Age | Sex | Vaccine, Dose | Time from Vaccine to Symptoms (Days) | Baseline VA | Eye | Systemic Conditions (Pre-Vaccination) | Manifestations | Outcome | Final VA |
---|---|---|---|---|---|---|---|---|---|---|---|
Elnahry et al., 2021 [19] | CS | 69 | F | BNT162b2, #2 | 16 | CF | OD | Hypertension, DM, cutaneous T-cell lymphoma | Blurry vision OU with immediate OS clearing but persistent blurring OD. The exam showed optic nerve head edema (OD > OS) and RAPD OD. OCT imaging and CSF confirmed a diagnosis of CNS inflammatory syndrome with neuroretinitis OD and papillitis OS. | Significant improvement of optic disc edema with stable vision after 5 days of IV methylprednisolone. | CF |
20/20 | OS | 20/20 | |||||||||
32 | F | COVISHIELD, #1 | 4 | 20/30 | OS | None | Blurred vision with superior field defect OS. Examination revealed optic disc swelling and RAPD with decreased RNFL thickness. MRI was consistent with optic neuritis | Significant improvement of optic nerve head swelling and improved VF defect and VA after 3 days of IV methylprednisolone followed by PO prednisone. | 20/20 | ||
Garcia-Estrada et al., 2021 [29] | CR | 19 | F | Ad26.COV2.S, #1 | 7 | 20/20 | OS | None | Ocular pain and vision loss OS, with exam revealing amaurosis, RAPD, and papillitis. | Resolution of symptoms and papillitis after 5 days of IV methylprednisolone followed by a PO prednisolone. | 20/20 |
Girbardt et al., 2021 [30] | CR | 67 | M | Vaxveria, #1 | 2 | 20/200 | OD | DM, hypercholesterolemia | Decreased vision and scotomas OD with exam revealing an elevated, congested optic nerve head with surrounding intraretinal hemorrhages and cotton-wool spots.NAION was diagnosed | NR | NR |
Leber et al., 2021 [31] | CR | 32 | F | Corona Vac, #2 | 0 | 20/200 | OS | NR | Rapidly progressive worsening vision and pain with EOM OS. Exam revealed RAPD OS and disc swelling OD and OS. MRI revealed optic neuritis OU. | Improvement in symptoms and vision after 5 days of IV methylprednisolone. | 20/20 |
20/20 | OD | 20/25 | |||||||||
Nachbor et al., 2021 [32] | CR | 64 | F | BNT162b2, #1 | 6 | 20/80 | OS | DM | Acute, painless, unilateral vision loss with superior sectoral optic disc edema OS after 1st dose. After 2nd dose, VA was CF with persistent APD OS. RNFL OCT showed diffuse thickening OS. NAION was diagnosed OS. | Improvement of symptoms with PO prednisone over 1 week. Resolution of optic disc edema followed by optic nerve pallor. | 20/100 |
Pawar et al., 2021 [33] | CR | 28 | F | AstraZeneca, #1 | 21 | 20/120 | OS | None | Sudden vision loss OS, with exam revealing mild blurring of the optic disc margin. MRI was consistent with optic neuritis OS. | Resolution of symptoms after IV methylprednisolone followed by PO steroid. | 20/20 |
Maleki et al., 2021 [34] | CR | 79 | F | BNT162b2, #2 | 2 | 20/1250 | OD | None | Bilateral sudden loss of vision, OD>OS, with 3+ RAPD OD. OCT, FA, ICG, and temporal artery biopsy consistent with consistent with bilateral AAION. | Initiated on subcutaneous tocilizumab. Prognosis was NR. | NR |
20/40 | OS | NR | |||||||||
Tsukii et al., 2021 [35] | CR | 55 | F | BNT162b2, #1 | 3 | 20/20 | OD | None | Visual disturbance with RAPD OD. Fundoscopy revealed diffuse optic disc swelling OD. An inferior VF defect suggesting AION. | vision remained normal and there was diffuse pallor OD, although no treatment was initiated | 20/20 |
Lin et al., 2022 [36] | CR | 61 | F | ChAdOx1nCoV-19 #1 | 7 | 20/50 | OS | Hypertension, hyperlipidemia | Scotoma in inferior field with hazy vision OS and headache. Fundus exam: optic disc edema OS. VF: inferior altitudinal field defect. OCT: peripapillary RNFL edema and GCL thinning in the superior macula. FA: filling delay, decreased choroidal perfusion, and optic disc leakage consistent with NAION OS. | PO prednisolone with gradual tapering. After 6 weeks, VA became 20/80 OS, and disc edema resolved | 20/80 |
Chung et al., 2022 [37] | CR | 65 | F | AstraZeneca #2 | 15 | CF | OD | None | RAPD OD. Fundus exam: a swollen disc with several splinter hemorrhages OD. VF: inferior arcuate and cecocentral visual field defects. OCT: thickened peripapillary RNFL and thinning of RNFL. MRI: no increased signal intensity or abnormal enhancement. NAION OD diagnosed | IV methylprednisolone followed by PO steroid taper. VA improved to 20/200 with optic disc pallor and no improvement in VF defect. | 20/200 |
Sanjay et al., 2022 [38] | CR | 52 | F | COVISHIELD #2 | 4 | 20/20 | OS | DM | Blurring of temporal disc margin with hyperemia OS. RAPD OS. Color vision was abnormal OU. NAION OS diagnosed. | PO aspirin for 1 month. BCVA OS was 20/20 at 1 month with resolved disc edema. | 20/20 |
Roy et al., 2022 [39] | CS | 27 | F | COVISHIELD #1 | 4 | 20/200 | OS | None | Progressive blurring of vision OS. RAPD and color desaturation OS. Fundus exam: diffuse swelling of the optic nerve head. VF: an enlarged blind spot. MRI brain and orbit: enhancement of left optic nerve just behind the disc. VEP: flat wave OS compared to OD. Diagnosed as optic neuritis OS. | IV methylprednisolone followed by PO steroid taper. BCVA improved to 20/40 OS with decreased disc swelling. | 20/40 |
48 | F | COVISHIELD #2 | 2 | 20/80 | OS | NR | RAPD OS. Fundus: swollen optic disc with blurred margins. OCT: peripapillary swelling of the retina. VF: an inferior arcuate defect. VEP: delayed latency and decreased amplitude OS. Optic neuritis OS was diagnosed | IV methylprednisolone. BCVA improved to 20/30 OS with improved VF. | 20/30 | ||
40 | M | COVISHIELD #1 | 5 | 20/200 | OD | NR | Sluggishly reacting pupils OU. Fundus: bilaterally blurred and swollen optic disc margin. VF: generalized depression OU. VEP: flat waves. Diagnosis of bilateral optic neuritis was made. | BCVA and VF improved OU after steroid therapy. | 20/30 | ||
20/200 | OS | 20/40 | |||||||||
Elhusseiny et al., 2022 [40] | CR | 51 | M | BNT162b2 #2 | 1 | CF 3 ft | OS | DM | Fundus exam: optic disc edema, peripapillary hemorrhages, and blunted foveal reflex OS. FA: optic disc leakage OS. OCT: marked thickening of the peripapillary retina, intraretinal fluid and hyperreflective foci consistent with exudates, and subretinal fluid under the fovea. NAION OS diagnosed. | PO prednisone over 1 month. Disc swelling and subretinal fluid resolved with BCVA of 20/400 OS. | 20/400 |
Madina et al., 2022 [41] | CS | 65 | F | BNT162b2 #1 | 5 | PL | OD | Medullary thyroid cancer, hypothyroidism, prediabetic, hyperlipidemia | Had vision loss and pain with eye movements OD. RAPD OD, optic disc swelling associated with cotton-wool spots and flame hemorrhages. MRI orbits: evidence of right optic neuritis. Optic neuritis OD diagnosed. | IV methylprednisolone and IVIG BCVA improved to 20/100 OD. | 20/100 |
67 | M | Moderna #2 | 1 | 20/40 | OD | Prediabetic, hyperlipidemia | bilateral eye redness, chemsosis, and blurring of vision. Had RAPD OS. MRI orbits: evidence of left optic neuritis. Optic neuritis OU diagnosed. | IV methylprednisolone. BCVA improved to 20/20 OD with a normal visual field, but he continued to have NPL OS. | 20/20 | ||
NPL | OS | NPL | |||||||||
Franco et al., 2022 [42] | CS | 53 | M | BNT162b2/Comirnaty vaccine #2 | 10 | 20/20 | OD | None | RAPD OS and fundus exam showed optic disc swelling with peripapillary hemorrhages OU. Disc edema confirmed by OCT OU. VF: constriction of peripheral visual field OS and an incomplete lower nasal scotoma OD. NAION OU diagnosed. | Stable BCVA with sluggish pupils. Fundus exam: pale discs OU without any hemorrhages. VF did not change OD, but OS was slightly better. | 20/20 |
20/40 | OS | 20/40 | |||||||||
65 | M | BNT162b2/Comirnaty vaccine #1 | 12 | 20/200 | OD | Hypertension | RAPD with optic disc swelling and peripapillary hemorrhages OD. NAION diagnosed. | No specific treatment was given. No vision improvement with dyschromatopsia (Ishihara test: 1/17), temporal optic disc pallor, and blind spot enlargement with centrocecal scotoma on VF. | 20/200 | ||
Norman et al., 2022 [43] | CS | 62 | M | BNT162b2 #1 | 6 | 20/20 | OS | None | RAPD OS. Inferior optic nerve swelling OS. VF: superior altitudinal defect. Diagnosed as presumed AON OS. | Stable BCVA and color vision, while VF continued to show superior altitudinal defect. Had complete resolution of disc edema, with some pallor and loss of the RNFL inferiorly. | 20/20 |
48 | F | BNT162b2 #1 | 5 | 20/70 | OD | Hypertension, migraine, asthma, trigeminal neuralgia | Trace RAPD OS. VF: paracentral scotoma OD with full field and no scotomas OS. Optic nerve head: temporal pallor and trace edema OD and temporal pallor OS. Labs: elevated ESR and CRP. Diagnosed as papillitis OU due to AON. | Started on steroids.VA improved OU, RAPD disappeared, with resolved disc swelling. | 20/50 | ||
20/200 | OS | 20/80 | |||||||||
38 | M | BNT162b2 #1 | 3 | 20/25 | OS | Hypertension, hyperlipidemia | Color Plates showed 12/14 OS with 2+ RAPD. VF: superior and inferior arcuate defects OS. Optic nerve head had a 0.1 cup-to-disc ratio with severe pallid edema, enlarged capillaries, and small disc hemorrhages. Diagnosed as presumed AON OS | IV methylprednisolone followed by PO steroid taper. Stable VA, persistent 2+ RAPD OS, with improved disc swelling and VF defects. | 20/25 | ||
Rizk et al., 2022 [44] | CR | 15 | M | BNT162b2 #2 | 7 | 20/200 | OD | None | No RAPD. Color vision: 8/17 OD and 6/17 OS. Hyperemic telangiectatic vessels on optic disc OU. VF: cecocentral scotoma OU. Diagnosis of LHON OU was confirmed genetically. | Started on idebenone 300 mg 3 times daily and counselled about lifestyle changes and triggers. | NR |
20/200 | OS | NR | |||||||||
Kumar et al., 2022 [45] | CR | 73 | M | COVISHEILD #1 | 5 | 20/1200 | OD | None | Bilateral sluggish and poorly sustained pupillary reactions. Exam: edematous disks and chorioretinal changes inferonasal to the disk OS. NAION diagnosed OU | Patient did not report any appreciable visual gain. | 20/1200 |
20/120 | OS | 20/120 | |||||||||
Che et al., 2022 [46] | CR | 87 | F | BNT162b2 #1 | 1 | HM | OD | Hypertension | Bilateral optic disc edema with focal disc hemorrhage. FFA: peripapillary choroidal filling delay in the vertical watershed zone OD. MRI: circumferential enhancement of the intraorbital portion of the optic nerve sheath bilaterally. Biopsy of the right temporal artery confirmed the diagnosis of GCA and AAION OU. | IV methylprednisolone followed by PO steroid taper. BCVA improved to 0.1 logMAR OS but worsened to NPL OD at 4 months after treatment. | NPL |
4 | 20/30 | OS | 20/25 | ||||||||
Raxwal et al., 2022 [47] | CR | 47 | F | Moderna #1 | 8 | 20/50 | OS | Hypertension | Blurring and RAPD OS. There was no pallor of the optic nerve and no evidence of papilledema OU. Optic neuritis diagnosed OS | IV methylprednisolone followed by PO steroid taper.. Follow-up revealed normal eye exam and normal VA. | 20/20 |
Wang et al., 2022 [48] | CS | 21 | F | Sinopharm #1 and #2 | 42 and 21 | 20/30 | OD | None | RAPD OD. Fundus exam: blurred optic disc margin with congestion and edema OD. FA: early hyperfluorescence and late enhancement of the right optic papilla. OCT: significant thickening of the RNFL. VF: central scotoma. VEP: decreased amplitude. MRI brain: a small ischemic focus in the left frontal lobe. orbital MRI: no significant abnormalities. Optic neuritis diagnosed OD. | IV methylprednisolone followed by PO steroid taper. Papillary congestion and edema OD gradually resolved. BCVA recovered to 1.0 after 1 month. | 20/20 |
38 | F | Sinopharm #1 | 21 | CF 1 m | OD | None | RAPD OD. Fundus exam: blurred borders of the optic disc with congestion and edema OD. FA: early hyperfluorescence of the optic papilla OD with late staining. OCT: significant thickening of RNFL. VEP: prolonged P100 wave latency and decreased amplitude. VF: centripetal narrowing. Orbital CT: hypointense thickening of optic nerve. Optic neuritis diagnosed OD. | IV methylprednisolone followed by PO steroid taper. Papillary congestion and edema gradually resolved OD. BCVA recovered to 1.0 after 1 month. | 20/20 | ||
Haseeb et al., 2022 [49] | CR | 40 | M | BNT162b2 #1 | 4 | 20/40 | OS | DM | Vision loss OS. Exam: RAPD OS and an edematous pale optic disc with blurred edges and splinter hemorrhages. FA: early leakage OS with late staining. NAION diagnosed OS | NR | NR |
Helmchen et al., 2022 [50] | CR | 40 | F | AstraZeneca #1 | 14 | NR | OD | Multiple sclerosis | Progressive diminution of vision over 48 h. CSF: severe pleocytosis, increased lactate and strongly elevated protein. Cranial MRI: numerous old white matter lesions compatible with MS and increased signal intensity in the chiasm, optic nerves and tracts. Mild optic chiasm enhancement was observed. VEP: unrecordable OU. Spinal MRI: increased longitudinal centrally located signal intensities throughout the thoracic myelon. Diagnosed with NMOSD and optic neuritis OU. | Two days after receiving IV methylprednisolone, there was no contrast enhancement visible. she was also treated with plasmapheresis and immunoadsorption with slight recovery of visual functions but paraplegia, loss of sensory function below T5, and incontinence persisted. Two months after subacute onset, with even more improved BCVA but unchanged paraplegia follow-up spinal | NR |
NR | OS | NR | |||||||||
Nagaratnam et al., 2022 [51] | CR | 36 | F | ChAdOx1nCoV-19 #1 | 12 | 20/50 | OD | None | CSF analysis on day 2 of admission showed a normal protein with pleocytosis. CSF oligoclonal IgG bands were present, suggestive of intrathecal IgG synthesis. VEP: unrecordable OS and delayed OD, consistent with demyelinating pathology of anterior visual pathways OU but OS>OD. MRI brain: multiple T2/ FLAIR hyperintense lesions in subcortical white matter, posterior limb of bilateral internal capsules, pons and left middle cerebellar peduncle. No definite abnormal signal or enhancement of optic nerves. Patient diagnosed with ADEM and optic neuritis OU. | IV methylprednisolone followed by PO steroid taper. VA improved to near baseline with full color vision OU. Both optic nerves were pale. | 20/16 |
20/100 | OS | 20/20 | |||||||||
Shirah et al., 2022 [52] | CR | 31 | F | BNT162b2 #1 | 14 | 20/20 | OS | Systemic lupus erythematosus | Diagnosed with SLE 10 years earlier. Fundus exam: normal OU without optic disc swelling. VF: paracentral VF contraction OU. Aquaporin-4 IgG antibody titer was positive at 1:1000. OCT: mild paracentral optic nerve thickening OS. VEP: mild to moderate prechiasmatic optic pathway dysfunction OS with secondary axonal loss. MRI: abnormal signal intensity and enhancement within the intraocular and intraorbital optic nerve OS. Optic neuritis diagnosed OS. | IV methylprednisolone followed by plasmapheresis, however, there was: no improvement. Rituximab was also started. Blurred vision OS remained unchanged, but ocular pain subsided. | 20/20 |
Pirani et al., 2022 [53] | CS | 31 | F | BNT162b2 #1 | 6 | 20/200 | OD | Ankylosing spondylitis | Fundus exam): mildly blurred margins of optic disc OD. VF showed scotoma OD. MRI brain, orbits and spine: no demyelination. T1-weighted MRI brain and orbits: enhancement of retrobulbar optic nerve OD; diagnosed with retrobulbar optic neuritis OD. | IV methylprednisolone followed by PO prednisone taper. On the third day BCVA improved to 20/20 OD. | 20/20 |
46 | F | BNT162b2 #1 | 8 | 20/40 | OD | Hashimoto thyroiditis | Slit-lamp exam OU was unremarkable. VF testing and MRI confirmed the diagnosis of retrobulbar optic neuritis OD. | IV methylprednisolone followed by PO steroid taper. BCVA improved to 20/25 OD and VF deficit resolved. | 20/25 | ||
Singu et al., 2022 [54] | CR | 39 | F | BNT162b2 #1 | 12 | 20/20 | OS | None | Ocular pain OS and headache without any other neurologic deficits. MRI: slight left optic neural swelling and perineuritis OS. Anti- MOG antibody: positive Diagnosed with optic neuritis and perineuritis OS. | Visual disturbance never recurred, and her ocular pain and headache subsided only with anti-inflammatory agents. | 20/20 |
Xia et al., 2022 [55] | CR | 68 | M | ChAdOx1nCoV-19 #2 | 29 | NPL | OS | Chronic obstructive pulmonary disease | Bilateral jaw claudication and profound lethargy, but no scalp tenderness, fever, weight loss, and no shoulder, neck, or hip pain. Labs: normal ESR with mildly elevated CRP. Bilateral temporal artery biopsy confirmed GCA. AAION diagnosed OS. | Treated with oral and IV steroids. Had episodes of blurred vision OD on day 3 so a fourth dose of methylprednisolone was given. | NPL |
Netravathi et al., 2022 [56] | CS | 29 | F | ChAdOx1nCoV-19 #1 | 11 | HM | OD | NR | RAPD OD. Anti-MOG- positive VEP: absent waveform OD, normal OS. MRI brain: T2 /FLAIR hyperintensity of long intraorbital segment of optic nerve OD with contrast enhancement. MOG-antibody-associated optic neuritis diagnosed OD. | IV methylprednisolone followed by PO steroid taper and plasmapheresis. | NR |
39 | M | ChAdOx1nCoV-19 #1 | 14 | CF | OD | NR | RAPD OD. VF: right inferonasal quadrant involvement. MOG-antibody-associated optic neuritis OD diagnosed. | IV methylprednisolone followed by PO steroid taper | NR | ||
54 | M | ChAdOx1nCoV-19 #1 | 14 | 20/40 | OS | NR | RAPD OS. VEP: normal OD, absent waveform OS. Anti-MOG: positive. MRI brain and spine: hyperintensity in Rt pons. MOG-associated optic neuritis diagnosed OS. | IV methylprednisolone followed by PO steroid taper | NR | ||
34 | M | ChAdOx1nCoV-19 #1 | 1 | PL | OD | NR | Non-reactive pupil OD. VEP: absent waveform OD. MRI: optic nerve tortuosity with prominent perioptic sheath and fat stranding OD. Optic neuritis diagnosed OD. | IV methylprednisolone followed by PO steroid taper | NR | ||
45 | F | ChAdOx1nCoV-19 #1 | 21 | 20/40 | OD | NR | RAPD OS. Normal pupillary reaction OD. MOG-associated optic neuritis diagnosed OU. | IV methylprednisolone followed by PO steroid taper and plasmapheresis. | NR | ||
HM | OS | NR | |||||||||
30 | M | ChAdOx1nCoV-19 #1 | 14 | NPL | OD | NR | Optic disc edema OU. VEP: non-recordable OU. CSF lymphocytosis. MRI brain: subcortical hyperintense foci in both cerebral hemispheres. MRI Optic nerves: OD>OS intraneural hyperintensities Optic neuritis diagnosed OU. | IV methylprednisolone followed by plasmapheresis and Rituximab. | NR | ||
20/600 | OS | NR | NR | ||||||||
40 | M | ChAdOx1nCoV-19 #1 | 10 | 20/60 | OD | NR | Serum MOG positive. MRI brain: T2 Hyperintensities in pons, bilateral thalami, right frontal cortex. MRI spine: longitudinally extensive myelitis. MOG-associated opticomyelopathy with optic neuritis OU diagnosed. | IV methylprednisolone followed by PO steroid taper and mycophenolate mofetil. | NR | ||
20/60 | OS | NR | NR | ||||||||
65 | F | ChAdOx1nCoV-19 #1 | 42 | HM | OD | NR | VEP OD non-recordable. CSF cells. Elevated ESR. NMO antibodies: positive. MRI brain: few hyperintensities in frontal subcortex. MRI Spine: hyperintensity with patchy contrast enhancement and bright spotty areas. NMO with optic neuritis OD diagnosed. | Received 3 cycles plasmapheresis followed by IV methylprednisolone then PO prednisolone 40 mg PO and mycophenolate mofetil. | NR |
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Elnahry, A.G.; Al-Nawaflh, M.Y.; Gamal Eldin, A.A.; Solyman, O.; Sallam, A.B.; Phillips, P.H.; Elhusseiny, A.M. COVID-19 Vaccine-Associated Optic Neuropathy: A Systematic Review of 45 Patients. Vaccines 2022, 10, 1758. https://doi.org/10.3390/vaccines10101758
Elnahry AG, Al-Nawaflh MY, Gamal Eldin AA, Solyman O, Sallam AB, Phillips PH, Elhusseiny AM. COVID-19 Vaccine-Associated Optic Neuropathy: A Systematic Review of 45 Patients. Vaccines. 2022; 10(10):1758. https://doi.org/10.3390/vaccines10101758
Chicago/Turabian StyleElnahry, Ayman G., Mutaz Y. Al-Nawaflh, Aisha A. Gamal Eldin, Omar Solyman, Ahmed B. Sallam, Paul H. Phillips, and Abdelrahman M. Elhusseiny. 2022. "COVID-19 Vaccine-Associated Optic Neuropathy: A Systematic Review of 45 Patients" Vaccines 10, no. 10: 1758. https://doi.org/10.3390/vaccines10101758