the process is ischemic optic neuropathy (ION) and both anterior ION and posterior ION have been reported with COVID19. Clinicians should be aware of the possibility of ION in COVID19.
- 1 Background
- 2 Summary
- 3 References
Ischemic optic neuropathy (ION) is a sudden, painless loss of vision due to an interruption of blood supply to the optic nerve. ION can be classified as anterior with disc edema (AION) or posterior without disc edema (PION). AION is typically divided into arteritic (A-AION) and non-arteritic (NA-AION) etiologies.
Recently, cases of optic neuropathy have been reported following infection with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that causes the Corona Virus Disease-19 (COVID19) . Proposed mechanisms of how SARS-CoV-2 might cause ION (AION or PION) include inducing a severe inflammatory response, endothelial damage, hypercoagulable state, and hypoxemia, which leads to hypoperfusion and subsequent ischemia of the optic nerve .
Typical non-COVID19 related NA-AION is associated with risk factors: (1) structural factors which make the optic nerve head susceptible to ischemic events (e.g., small cup to disc ratio or “disc at risk”) and (2) vascular factors which predispose to acute hypoperfusion of the optic nerve head (e.g., diabetes mellitus, systemic hypertension, nocturnal arterial hypotension, ischemic heart disease, anemia). Non-arteritic posterior ischemic optic neuropathy (NA-PION) is thought to have similar vascular risk factors as NA-AION, but no structural risk has been found. Typical AION is the common presentation, while PION is rare.
Pathophysiology of COVID19-related ION
The coronavirus has been reported to cause activation of inflammatory cells (e.g. neutrophils and monocytes) and endothelial cells leading to high levels of circulating inflammatory cytokines (e.g., CRP, ferritin, IL-2, TNF-α) and excess production of pro-coagulants (e.g., tissue factor and von Willebrand factor) . Extensive complement involvement and membrane attack complex-mediated microvascular endothelial cell injury have also been reported to lead to COVID19-associated coagulopathy, which can include venous, arterial, and microvascular thrombosis. COVID19 has also been reported to cause clinically significant hypoxemia.
In ION, it has been hypothesized that these factors in COVID19 (inflammatory response, hypercoagulable state, and hypoxemia) may lead to thrombosis of the blood vessels (e.g., ciliary vessels) supplying the optic nerve and subsequent ischemia of the optic nerve. However, there have been no studies to confirm this pathogenesis.
Savastano et al. reported the impact of SARS-CoV-2 infection on the microvascular network of optic nerve head in patients who recovered from COVID19. The study reported that in the patients who recovered from COVID19, there was an impairment in the blood supply to the peripapillary retinal nerve fiber layer, characterized by a reduction of radial peripapillary capillary plexus (RPCP) density. RPCP density has been previously correlated to visual acuity and visual field loss in NAION patients.
Case Reports of Presumed ION after COVID19 Infection
|Case||Sex||Age||Past Medical History||Ophthalmic Symptoms||Physical Exam||Labs||Diagnosis|
|1||F||50||HTN, HLD||Acute, painless vision loss OD; 1 week after testing positive for COVID||20/70 OD. Temporal and inferior nasal field loss OD.No RAPD. Normal fundoscopic exam with no optic disc edema.||Normal CBC, BMP, ESR. CRP 7 and d dimer 206 ng/ml.||PION|
|2||M||52||None||Acute, painless vision loss and floater OD; 2 weeks after COVID hospitalization||Hand motion perception OD. RAPD OD. Central and nasal field loss OD.Pale optic disc without swelling OD, small optic disc OS.||ESR 42 (high), CRP 39 (high). Lymphopenia (WBC 6800/ul; lymphocyte: 11.5%)||NAION|
|3||M||43||DM, HLD||Acute, painless vision loss OD; 4 weeks after COVID symptoms and testing positive||20/30 OD. RAPD OD. Inferior hemifield defect OD. Temporal pallor of optic nerve OD.||Normal CBC, ESR, BMP.||NAION|
|4||M||45||DM, HTN||Acute, blurry vision OD followed by blurry vision OS 2 weeks later; started 1 month after COVID-19 infection||6/6 OD, 6/24 OS. RAPD OS. Inferior field defect OS. Superior and inferior field defects OS. Hyperemic optic disc with blurred margins (OD), pale edematous disc (OS).||Normal CBC, ESR, BMP.||Bilateral sequential NAION|
|5||F||67||CAD s/p PCI 7 years ago, HTN||Decreased vision OS preceded by 2-day headache; tested positive for Sars-CoV-2 2 days later||20/800 OS (with dense posterior subcapsular cataract). No RAPD. Superior visual field loss OS.||Normal labs||NAION|
|6||F||69||DM, HTN||Vision loss OS with severe headaches near eyes and occiput, and scalp tenderness; 2.5 weeks after positive SARS-CoV-2 test||Light perception from nasal and superior side OS. No direct response and slow indirect response to light OS. Blurring of optic margins with flame hemorrhages OS.||Elevated ESR (63 mm/h; range, 3-15 mm/h). Ultrasound of temporal arteries revealed wall thickening and a “halo.”||GCA/AAION|
|7||M||72||DM, HTN, smoking||Acute, painless, blurred vision OD; 13 days after COVID-19 symptoms||0.3 OD. No RAPD. Inferior visual field loss OD. Optic disc swelling OD.||Normal labs||NAION|
|8||M||64||None||Vision loss OD; 5 weeks after COVID-19 symptoms and hospitalization||20/20 OD. RAPD OD. Inferior visual field loss OD. Pale optic disc with sectorial papillary edema OD||Normal labs||NAION|
About 40% of patients with non-COVID19 related NAION will spontaneously recover some vision.
While there are no definite treatments for NAION, the underlying cause should be treated to prevent further complications. Risk factors for atherosclerosis should be controlled, including blood pressure and diabetes. Most of the recommended treatments are intended to prevent thrombosis (e.g., aspirin) or reduce the edema of the optic disc . While corticosteroids can lead to improvement in systemic symptoms and prevention of blindness in arteritic ION/giant cell arteritis (GCA), corticosteroids are not suggested for NAION. In the context of COVID19, the benefits of steroids have not been explored.
Optic neuropathy has been reported in COVID19 and the mechanisms remain ill defined although several hypotheses have been proposed including inflammatory cytokines and a transient hypercoagulable state. Many authors believe that the process is ION and both AION and PION have been reported with COVID19. Further work is necessary to confirm if the optic neuropathy is truly ischemic in origin and what potential treatments might be considered. In typical AION the major diagnostic dilemma is differentiating arteritic (i.e., giant cell arteritis) from non-arteritic AION (NAION). In the setting of COVID19 infection, the acute phase reactants (e.g., ESR, CRP, platelet count) might be elevated and mistaken for signs of GCA. Evaluation for A-AION and GCA in elderly patients including temporal artery biopsy might still be necessary however and some of the cases of AION and COVID19 in the literature may have been coincidental (GCA) and not causal. Clinicians should be aware of the possibility of ION in COVID19.
- ↑ Jump up to:1.0 1.1 1.2 Hayreh S. S. (2011). Management of ischemic optic neuropathies. Indian journal of ophthalmology, 59(2), 123–136. https://doi.org/10.4103/0301-4738.77024
- ↑ Jump up to:2.0 2.1 2.2 Selvaraj V, Sacchetti D, Finn A, Dapaah-Afriyie K. (2020). Acute Vision Loss in a Patient with COVID-19. Rhode Island Medical Journal, 103(6), 37-38.
- ↑ Jump up to:3.0 3.1 3.2 3.3 3.4 Golabchi, K., Rezaee, A., Aghadoost, D., & Hashemipour, M. (2021). Anterior ischemic optic neuropathy as a rare manifestation of COVID-19: a case report. Future virology, 10.2217/fvl-2021-0068. https://doi.org/10.2217/fvl-2021-0068
- ↑ Jump up to:4.0 4.1 4.2 Rho, J., Dryden, S. C., McGuffey, C. D., Fowler, B. T., & Fleming, J. (2020). A Case of Non-Arteritic Anterior Ischemic Optic Neuropathy with COVID-19. Cureus, 12(12), e11950. https://doi.org/10.7759/cureus.11950
- ↑ Jump up to:5.0 5.1 5.2 Sanoria, A., Jain, P., Arora, R., & Bharti, N. (2022). Bilateral sequential non-arteritic optic neuropathy post-COVID-19. Indian journal of ophthalmology, 70(2), 676–679. https://doi.org/10.4103/ijo.IJO_2365_21
- ↑ Jump up to:6.0 6.1 6.2 6.3 Babazadeh, A., Barary, M., Ebrahimpour, S., Sio, T. T., & Mohseni Afshar, Z. (2022). Non-arteritic anterior ischemic optic neuropathy as an atypical feature of COVID-19: A case report. Journal francais d’ophtalmologie, 45(4), e171–e173. https://doi.org/10.1016/j.jfo.2021.12.001
- ↑ Jump up to:7.0 7.1 7.2 Szydełko-Paśko, U., Przeździecka-Dołyk, J., Kręcicka, J., Małecki, R., Misiuk-Hojło, M., & Turno-Kręcicka, A. (2022). Arteritic Anterior Ischemic Optic Neuropathy in the Course of Giant Cell Arteritis After COVID-19. The American journal of case reports, 23, e933471.
- ↑ Jump up to:8.0 8.1 8.2 Yüksel, B., Bıçak, F., Gümüş, F., & Küsbeci, T. (2021). Non-Arteritic Anterior Ischaemic Optic Neuropathy with Progressive Macular Ganglion Cell Atrophy due to COVID-19. Neuro-ophthalmology (Aeolus Press), 46(2), 104–108.
- ↑ Jump up to:9.0 9.1 9.2 Moschetta, L., Fasolino, G., & Kuijpers, R. W. (2021). Non-arteritic anterior ischaemic optic neuropathy sequential to SARS-CoV-2 virus pneumonia: preventable by endothelial protection?. BMJ case reports, 14(7), e240542. https://doi.org/10.1136/bcr-2020-240542
- ↑ Kaur, S., Bansal, R., Kollimuttathuillam, S., Gowda, A. M., Singh, B., Mehta, D., & Maroules, M. (2021). The looming storm: Blood and cytokines in COVID-19. Blood reviews, 46, 100743. https://doi.org/10.1016/j.blre.2020.100743
- ↑ Jump up to:11.0 11.1 Magro, C., Mulvey, J. J., Berlin, D., Nuovo, G., Salvatore, S., Harp, J., Baxter-Stoltzfus, A., & Laurence, J. (2020). Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases. Translational research : the journal of laboratory and clinical medicine, 220, 1–13. https://doi.org/10.1016/j.trsl.2020.04.007
- ↑ Jump up to:12.0 12.1 Goshua, G., Pine, A. B., Meizlish, M. L., Chang, C. H., Zhang, H., Bahel, P., Baluha, A., Bar, N., Bona, R. D., Burns, A. J., Dela Cruz, C. S., Dumont, A., Halene, S., Hwa, J., Koff, J., Menninger, H., Neparidze, N., Price, C., Siner, J. M., Tormey, C., … Lee, A. I. (2020). Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. The Lancet. Haematology, 7(8), e575–e582. https://doi.org/10.1016/S2352-3026(20)30216-7
- ↑ Jump up to:13.0 13.1 Tobin, M. J., Laghi, F., & Jubran, A. (2020). Why COVID-19 Silent Hypoxemia Is Baffling to Physicians. American journal of respiratory and critical care medicine, 202(3), 356–360. https://doi.org/10.1164/rccm.202006-2157CP
- ↑ Jump up to:14.0 14.1 14.2 Sadda SR, Nee M, Miller NR, Biousse V, Newman NJ, Kouzis A. (2001). Clinical spectrum of posterior ischemic optic neuropathy. American Journal of Ophthalmology, 132(5):743-750.
- ↑ Savastano, A., Crincoli, E., Savastano, M. C., Younis, S., Gambini, G., De Vico, U., Cozzupoli, G. M., Culiersi, C., Rizzo, S., & Gemelli Against Covid-Post-Acute Care Study Group (2020). Peripapillary Retinal Vascular Involvement in Early Post-COVID-19 Patients. Journal of clinical medicine, 9(9), 2895. https://doi.org/10.3390/jcm9092895
- ↑ Jump up to:16.0 16.1 Garrity, J. (2021). Ischemic Optic Neuropathy. Merck Manual. https://www.merckmanuals.com/home/eye-disorders/optic-nerve-disorders/ischemic-optic-neuropathy
- ↑ Aiello, P. D., Trautmann, J. C., McPhee, T. J., Kunselman, A. R., & Hunder, G. G. (1993). Visual prognosis in giant cell arteritis. Ophthalmology, 100(4), 550–555. https://doi.org/10.1016/s0161-6420(93)31608-8