Optic Neuropathy after COVID-19

Authors: Alicia ChenAndrew Go Lee, MDNagham Al-Zubidi, MDNoor LaylaniPamela Davila-Siliezar American Academy of Ophthalmology

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.

Contents

Background

Ischemic optic neuropathy (ION) is a sudden, painless loss of vision due to an interruption of blood supply to the optic nerve[1]. 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[1].

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)[2] [3][4][5][6][7][8][9]. 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[3] [10][11][12][13].

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)[1]. 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[14]. Typical AION is the common presentation, while PION is rare[14].

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)[3] [11]. 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[12][13]. COVID19 has also been reported to cause clinically significant hypoxemia[14].

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[2][3][4][5][7][8][9]. 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[15].

Case Reports of Presumed ION after COVID19 Infection

CaseSexAgePast Medical HistoryOphthalmic SymptomsPhysical ExamLabsDiagnosis
1[2]F50HTN, HLDAcute, painless vision loss OD; 1 week after testing positive for COVID20/70 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[3]M52NoneAcute, painless vision loss and floater OD; 2 weeks after COVID hospitalizationHand 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[4]M43DM, HLDAcute, painless vision loss OD; 4 weeks after COVID symptoms and testing positive20/30 OD. RAPD OD. Inferior hemifield defect OD. Temporal pallor of optic nerve OD.Normal CBC, ESR, BMP.NAION
4[5]M45DM, HTNAcute, blurry vision OD followed by blurry vision OS 2 weeks later; started 1 month after COVID-19 infection6/6 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[6]F67CAD s/p PCI 7 years ago, HTNDecreased vision OS preceded by 2-day headache; tested positive for Sars-CoV-2 2 days later20/800 OS (with dense posterior subcapsular cataract). No RAPD. Superior visual field loss OS.Normal labsNAION
6[7]F69DM, HTNVision loss OS with severe headaches near eyes and occiput, and scalp tenderness; 2.5 weeks after positive SARS-CoV-2 testLight 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[8]M72DM, HTN, smokingAcute, painless, blurred vision OD; 13 days after COVID-19 symptoms0.3 OD. No RAPD. Inferior visual field loss OD. Optic disc swelling OD.Normal labsNAION
8[9]M64NoneVision loss OD; 5 weeks after COVID-19 symptoms and hospitalization20/20 OD. RAPD OD. Inferior visual field loss OD. Pale optic disc with sectorial papillary edema ODNormal labsNAION

Prognosis

About 40% of patients with non-COVID19 related NAION will spontaneously recover some vision[16].

Treatment

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[16]. Most of the recommended treatments are intended to prevent thrombosis (e.g., aspirin) or reduce the edema of the optic disc [6]. 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[17]. In the context of COVID19, the benefits of steroids have not been explored[6].

Summary

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.

References

  1. ↑ Jump up to:1.0 1.1 1.2 Hayreh S. S. (2011). Management of ischemic optic neuropathies. Indian journal of ophthalmology59(2), 123–136. https://doi.org/10.4103/0301-4738.77024
  2. ↑ 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.
  3. ↑ 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
  4. ↑ 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. Cureus12(12), e11950. https://doi.org/10.7759/cureus.11950
  5. ↑ 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 ophthalmology70(2), 676–679. https://doi.org/10.4103/ijo.IJO_2365_21
  6. ↑ 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’ophtalmologie45(4), e171–e173. https://doi.org/10.1016/j.jfo.2021.12.001
  7. ↑ 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 reports23, e933471.
  8. ↑ 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.
  9. ↑ 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 reports14(7), e240542. https://doi.org/10.1136/bcr-2020-240542
  10.  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 reviews46, 100743. https://doi.org/10.1016/j.blre.2020.100743
  11. ↑ 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
  12. ↑ 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. Haematology7(8), e575–e582. https://doi.org/10.1016/S2352-3026(20)30216-7
  13. ↑ 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 medicine202(3), 356–360. https://doi.org/10.1164/rccm.202006-2157CP
  14. ↑ 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.
  15.  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 medicine9(9), 2895. https://doi.org/10.3390/jcm9092895
  16. ↑ 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
  17.  Aiello, P. D., Trautmann, J. C., McPhee, T. J., Kunselman, A. R., & Hunder, G. G. (1993). Visual prognosis in giant cell arteritis. Ophthalmology100(4), 550–555. https://doi.org/10.1016/s0161-6420(93)31608-8

COVID-19-associated optic neuritis – A case series and review of literature

Authors: Jossy, Ajax; Jacob, Ninan; Sarkar, Sandip; Gokhale, Tanmay; Kaliaperumal, Subashini; Deb, Amit K IJO Ophthalmology

Abstract

Neuroophthalmic manifestations are very rare in corona virus disease-19 (COVID-19) infection. Only few reports have been published till date describing COVID-19-associated neuroophthalmic manifestations. We, hereby, present a series of three cases who developed optic neuritis during the recovery period from COVID-19 infection. Among the three patients, demyelinating lesions were identified in two cases, while another case was associated with serum antibodies against myelin oligodendrocyte glycoprotein. All three patients received intravenous methylprednisolone followed by oral steroids according to the Optic Neuritis Treatment Trail ptotocol. Vision recovery was noted in all three patients, which was maintained at 2 months of the last follow up visit.

COVID-19 infection predo minantly causes a respiratory illness, but it can have a myriad of symptoms, affecting almost all organs of the body.[1] Varied ocular manifestations including conjunctivitis, episcleritis, vascular occlusions, dacryoadenitis, mucormycosis, etc., have been reported in COVID-19 infection.[2] Neuroophthalmic manifestations in COVID-19 infection are uncommon, but they can seldom develop either during the active course or the recovery period.[3] Neuroophthalmic manifestations of COVID-19 infection includes optic neuritis, acute transverse myelitis, viral encephalitis, toxic encephalopathy, leukoencephalopathy, acute disseminated encephalomyelitis, diffuse corticospinal tract signs, etc.[4] Only a handful reports of optic neuritis associated with COVID-19 infection with or without demyelinating lesions have been published. Few of them are associated with serum antibodies against myelin oligodendrocyte glycoprotein (MOG).[567891011121314151617181920] In this report, we describe the clinical profile and treatment outcome of three patients who developed optic neuritis during recovery from COVID-19 infection.

Case Reports

Case 1

A 16-year-old boy presented with sudden gross diminution of vision in the left eye (LE) for 3 days with headache and eyepain on extraocular movements. His past history was unremarkable. The patient had tested positive for COVID-19 infection with reverse transcription polymerase chain reaction (RT-PCR) 2 weeks prior to the incident. He was advised home isolation without any supplemental oxygen or steroids. Systemic and neurological examinations were unremarkable. On ocular examination, best-corrected visual acuity (BCVA) was 20/20 in the right eye (RE) and perception of light (PL+) in the LE, with a grade 2 relative afferent pupillary defect in the LE. Fundus examination revealed normal optic discs in both eyes with no evidence of disc edema or hyperemia [Fig. 1a and 1b]. A diagnosis of LE retrobulbar neuritis was made. Laboratory investigations, imaging, treatment received, and disease course are provided in Table 1.

F1
Figure 1: Fundus images of both eyes at presentation showing normal disc and macula (a and b), magnetic resonance imaging of the orbits at presentation (c) showing hyperintense lesion in the left optic nerve (red arrow), and pattern visual evoked potential at 1 week (d) showing increased latency and decreased amplitudes in the left eye
T1
Table 1: Investigation and treatment details of all cases

Case 2

A 35-year-old male presented with sudden vision loss in LE with pain on extraocular movements for 1 week. His past history was unremarkable. He was tested positive for COVID-19 infection with RT-PCR 6 months prior to the vision loss. He was advised home isolation and did not require oxygen or steroids for COVID-19. On ocular examination, BCVA was 20/20 in RE and 20/600 in LE, with grade I RAPD in LE. Fundus examination of the LE revealed edematous disc with blurred margins and peripapillary edema, which was confirmed on optical coherence tomography, while the RE fundus was normal [Fig. 2a and 2b]. A diagnosis of LE papillitis was made. Laboratory investigations, imaging, treatment, and disease course are described in Table 1.

F2
Figure 2: Fundus image of RE (a) showing normal disc and macula and LE (b) showing an edematous disc with blurred margins and peripapillary edema, magnetic resonance imaging of the orbits (c) showing normal findings; visual evoked potential performed 2 weeks after presentation (d) showed minimally increased latency with decreased amplitude in the left eye

Case 3

A 38-year-old male presented with sudden gross diminution of vision and pain on extraocular movements in the LE for 5 days. The patient had a similar complaint in the LE 1 month ago. He was treated elsewhere for the same with intravenous methylprednisolone and oral prednisolone. There was symptomatic improvement in the vision within a week following the initiation of treatment. However, he noticed another similar episode of decreased vision in the LE 3 weeks later, when he presented to us. He was tested positive for COVID-19 infection with RT-PCR one-and-half month prior to the current episode. He was advised home isolation, and he also did not require oxygen or steroids for COVID-19 infection. Systemic examination was unremarkable. On ocular examination, BCVA was RE 20/20 and LE hand movements (HM+), with grade III RAPD in the LE. Fundus examination showed normal discs in both eyes [Fig. 3a and 3b]. A diagnosis of LE retrobulbar neuritis was made. Laboratory investigations, imaging findings, treatment, and disease course are described in Table 1.

F3
Figure 3: Fundus image of both eyes (a) & (b) showing normal disc and macula, magnetic resonance imaging of the orbits (c) showing hyperintense lesion in the optic nerves of both eyes (red arrows), and flash VEP (d) showed normal N2-P2 latency with decreased amplitudes in both the eyes

Discussion

Optic neuritis is an inflammatory demyelinating optic neuropathy causing acute uniocular or binocular loss of vision.[21] Optic neuritis is mainly a clinical diagnosis based on history and examination findings. Investigations like magnetic resonance imaging, lumbar puncture, and antibodies against AQP4 and MOG help in finding the association and cause of vision loss.[21] Once the diagnosis is established, treatment is done based on optic neuritis treatment trial (ONTT) protocol.[22]

Neurotropism of the virus was postulated as one of the mechanisms for neuroophthalmic manifestations.[2] Another mechanism involves molecular mimicry where the viral antigens trigger host immune response directed toward the CNS myelin proteins.[46] All the three cases reported by us had viral prodromes and positive COVID-19 infection. It is interesting to note that all three cases had mild COVID-19 infections with no oxygen requirement or steroid use, and their recoveries were uneventful. Vision loss in all the three cases happened during the recovery period of the infections and dramatic response to steroids points toward an inflammatory disorder triggered by the viral antigen. In the third case, the patient had two similar episodes of vision loss in 2 months after the COVID-19 infection. He was tested positive for MOG antibody. MOG antibody-associated optic neuritis usually has good visual recovery with good response to steroids but shows bilaterality and recurrence. Our case also showed initial good response to systemic steroids with recurrence within 2 weeks of discontinuation of steroids. MOG antibody-associated optic neuritis in COVID-19 infection has been reported by Zhou et al.,[6] Zoric et al.,[10] Kugure et al.,[12] Sawalha et al.,[5] de Ruijter et al.,[14] Rojas-Correa et al.[19]. Table 2 describes the details of all cases of COVID-19-associated optic neuritis. Due to the ongoing COVID-19 pandemic, we can expect more similar cases in future. So, prospective studies are warranted to establish the relationship between the viral antigen, severity of COVID-19 infection, and associated optic neuritis.

T2
Table 2: Summary of all the published studies

Conclusion

Neuro-ophthalmic manifestations are rare in COVID-19 infection, and can be seen either during the active disease phase or the recovery phase.[3] Optic neuritis is one such rare manifestation. The three cases of optic neuritis being reported by us had mild COVID-19 infection. Two cases developed ocular symptoms and signs within the first six weeks of recovery while another case developed ocular manifestations six months after recovery from COVID-19. All the three cases showed good response to systemic steroids with significant visual recovery. Keeping the ongoing pandemic in perspective, we should, therefore, be vigilant in identifying the neuro-ophthalmic features of COVID-19 infection to prevent irreversible vision loss.

Covid-19 Complications Can Lead To Total Vision Loss, Eye Damage.

Authors:  Parmita Uniyal Only My Health April 2022

Apart from the common symptoms of Covid-19, pink eye or conjunctivitis is seen in 1-3% of people suffering from the deadly virus. The eyes of the patients displaying this symptom tend to become slightly painful and red with pricking sensation and watering. With time, ophthalmologists are gaining more insight on the disease and the impact it can have on eyes. It has now emerged that COVID-19 can actually lead to a variety of eye complications which may affect retina as well as its nerve. In some cases, the patient may completely lose vision or it may get deteriorated. It can also lead to permanent and irreversible damage to the eye. Timely treatment is the key and in most of the cases, the condition will improve with proper medication.

Dr. Bhanu Prakash, Sr. Consultant Ophthalmologist, Dr. Agarwals Eye Hospital talks about the Covid-19 complications that can also result in vision loss and irreversible damage to the eye.

How Covid-19 Can Result In Total Or Partial Vision Loss

Apart from the pink eye, there are some other concerning eye-related issues that the Covid-19 patients are facing. The issues if not addressed on time can cause permanent damage to eyes. According to Dr. Prakash, the disease may affect retina as well as its nerve and can lead to formation of blood clots in the patient’s body which can in turn block blood vessels in the retina. “The patient may not notice anything wrong if the blocked blood vessel is minor or carries deoxygenated blood. However, in some cases, the main blood vessel carrying oxygenated blood to the eyes gets impacted by the virus, leading to deterioration or total loss of the patient’s vision,” he says.

How Covid-19 Can Cause Retinitis or Localized Inflammation

Blocked blood vessels are not the only eye morbidity associated with Covid. Some patients may develop localized inflammation called retinitis. According to American Society of Retina Specials, infectious retinitis is an inflammation of the retina resulting from infection by viruses, bacteria, fungi, or parasites. This is again treatable with medicines or injections.

How It Can Be Treated

While the prospect of permanent eye damage may be scary, timely treatment of the condition can help in most of the cases.  Timely diagnosis and proper management of the condition is the key. 

If the patient reaches an ophthalmologist within 6 hours of vision loss, his or her sight can be saved. With prompt action, blood circulation in the eyes can be restored. In these cases, almost 100% or 95% vision of the patient can be restored. However, delay or complacency in reaching an ophthalmologist quickly can lead to permanent and irreversible damage to the eye. 

Usage of Steroids Can Lead To Cataract

Dr Prakash says steroids which are commonly used for the treatment of Covid can cause damage to the eyes as well. A category of patients called “steroid responders” tend to develop an increase in fluid pressure in their eyes when administered steroids. This condition can damage the eyes. In some cases that involve long-term use of steroids, patients can develop cataract. Timely checkup can avoid such complications, reversing the side-effects of steroids and saving the patient’s vision.

As per an article in American Academy of Ophthalmology, consider the following as the warning signs to visit your eye doctor:

  1. If you have a blurry, wavy vision or black spots in the field of your vision.
  2. You have an eye injury
  3. You suddenly lose vision
  4. You have a red eye or pain in your eyes and if associated with headache, nausea or vomiting.

Tips for eye care by Sonal Tuli, a spokesperson for the American Academy of Ophthalmology, as published in the article:

  1. If you wear contact lenses, consider switching to glasses for a while as the person who wears lenses may touch eyes more often.
  2. Try to opt for sunglasses to guard from eyes from any infection
  3. Avoid touching your eyes as doing this can reduce risk of infection
  4. Wear a mask. Wash your hands

It is important to pay attention to your eye health in pandemic times and otherwise. If you have recently recovered from COVID, then any kind of pain or inflammation should be followed by a visit to your ophthalmologist. Timely treatment and some easy precautions can save you from getting permanent eye issues. Washing your hands from time to time and not touching eyes or face frequently is something that COVID has taught us and it will go a long way in preventing eye infections too.

Covid Linked To Disorder That Causes Sudden Vision Loss, Study Says

Authors: Zachary Snowdon Smith Forbes 

Covid-19 infection is linked to eye conditions called retinal vascular occlusions—blockages of blood vessels in the eye that can cause vision loss—according to a study published Thursday by JAMA Ophthalmology that threw light on one of several little-understood long-term effects of the virus.

KEY FACTS

The first condition, called retinal artery occlusions, can cause sudden blurring or loss of vision in one eye, and was found to have increased 29.9% in the period two to 26 weeks after Covid-19 diagnosis compared to the period 26 to two weeks before diagnosis, researchers concluded.

The second condition, retinal vein occlusions, causes similar symptoms to retinal artery occlusions and was even more strongly associated with Covid-19, with a 47% increase in the period two to 26 weeks after Covid-19 diagnosis compared to the period 26 to two weeks before diagnosis, according to the study.

The strong association between Covid-19 and retinal vein occlusions seems to confirm previous research suggesting that Covid-19 generally affects veins more severely than arteries, researchers said—a finding that could help guide treatment approaches for Covid-19 patients.

Even following Covid-19 infection, retinal vascular occlusions remained rare, with retinal artery occlusions affecting about 1 in 333,333 patients and retinal vein occlusions affecting about 1 in 81,967 patients during the period two to 26 weeks after they were diagnosed.

Researchers did not find that Covid-19 patients who were hospitalized were more likely to experience retinal vascular occlusions than those who were not hospitalized.

The study included 432,515 patients without a history of retinal vascular occlusions more than six months prior to their Covid-19 diagnosis, and who were diagnosed with the virus between January 20, 2020 and May 31, 2021.

TANGENT

Retinal vascular occlusions are caused when blood clots or fat deposits block blood vessels in the retina, the part of the eye that receives light and transmits images to the brain. These occlusions may cause damage ranging from slight vision impairments to whole-eye vision loss. Retinal artery occlusion is linked to diabetes, high blood pressure, elevated levels of fat in blood and various disorders affecting the heart or the carotid artery, according to the National Library of Medicine’s MedlinePlus service. Retinal vein occlusion is linked to diabetes, high blood pressure, fatty buildup in the arteries and eye disorders like glaucoma. Outcomes are variable: while many patients regain a degree of vision, there are no reliable treatments for whole-eye vision loss due to a retinal vascular occlusion. These occlusions may indicate the presence of clots or fat deposits elsewhere in the body, warning of a risk of stroke, according to Johns Hopkins Medicine.

KEY BACKGROUND

Though Covid-19’s immediate symptoms have been well documented, scientists have struggled to understand the longer-term effects of the virus. A study published Monday by JAMA Neurology determined that the long-term smell loss reported by some Covid-19 patients is tied to damage to the olfactory bulb, the part of the brain that processes smells. Covid-19 has also been associated with a range of vascular issues such as inflammation of the heart muscle or the sac containing the heart. Some researchers have concluded that much of the damage caused by the coronavirus is not directly inflicted by the virus itself, but by infection symptoms like inflammation, the New York Times reports. The authors of the JAMA Ophthalmology study suggested a similar interpretation, theorizing that the initial vascular damage caused by Covid-19 infection might make some people more vulnerable to a pre-existing risk of retinal vascular occlusions.

CONTRA

It’s possible that the JAMA Ophthalmology study underestimated the risk of retinal vascular occlusions among severely ill patients because those patients’ conditions may have prevented them from informing healthcare staff of vision changes, researchers said.

WHAT WE DON’T KNOW

Further research would be necessary to establish a cause-and-effect relationship between Covid-19 infection and retinal vascular occlusions, researchers said. The JAMA Ophthalmology study established only an association between the two conditions.

Vision-Threatening Ocular Adverse Events after Vaccination against Coronavirus Disease 2019

Authors: Mihyun Choi 1Min-Hwan Seo 1Kwang-Eon Choi 2Sukyeon Lee 1Boyoon Choi 1Cheolmin Yun 2Seong-Woo Kim 1Yong Yeon Kim 1 J Clin Med 2022 Jun 9;11(12):3318. doi: 10.3390/jcm11123318.

Abstract

A single-center retrospective observational case series was conducted. This case series enrolled patients who showed ophthalmic manifestations within one week after COVID-19 vaccination at Korea University Guro Hospital in Seoul, Korea, from May 2021 to January 2022. The medical records of patients who complained of ocular symptoms and showed ophthalmic adverse events within one week after COVID-19 vaccination were reviewed. Seventeen eyes from 16 patients with a mean age of 63.8 (range 33–83) years were included in the case series, and all symptoms developed within 1–7 days following inoculation. Retinal vein occlusion in nine eyes (52.9%), retinal artery occlusion in one eye (5.9%), newly developed anterior uveitis in one eye (5.9%), exacerbation of previously diagnosed panuveitis in two eyes (11.8%), and angle-closure attack with high intraocular pressure in four eyes (23.5%) were included. Twelve patients (75%) had been vaccinated with the AstraZeneca (AZD1222) and four (25%) with the Pfizer (BNT162b2) vaccines. Of these, 10 patients (62.5%) experienced ocular disease exacerbation after the first dose, 4 (25%) after the second dose, and 2 (12.5%) after the third dose (booster shot). Eleven patients (64.7%) underwent tests for hematological abnormalities, and three of them tested positive for anti-PF4 antibodies, but no abnormal findings were noted. A causal relationship between vaccination and the ocular manifestations could not be determined, which is a limitation of this study. However, clinicians should consider the effect of COVID-19 vaccination on ophthalmic disease. Further studies are required to elucidate the possible effects of COVID-19 vaccination on the eye. View Full-Text

Keywords: vaccinationSARS-CoV-2COVID-2019ocular adverse eventsvascular occlusionsuveitisangle-closure glaucoma

▼ Show Figures

Figure 1

1. Introduction

On 13 May 2021, the Royal College of Ophthalmologists in the United Kingdom issued a safety alert for retinal vein occlusion (RVO) in the immediate period (28 days) after vaccination for coronavirus disease 2019 (COVID-19) [1]. Vaccination against COVID-19 is now being conducted worldwide. In Korea, COVID-19 vaccinations began in March 2021, first among health care workers and vulnerable members of the community in March and April, and then expanded to all individuals older than 60 years of age in May and June. The AstraZeneca (AZD1222) and Pfizer (BNT162b2) vaccines are the two mainstays of the government-driven, nation-scale vaccination program initiated in South Korea. Approximately 20 million people were vaccinated as of August 2021, with those who received the AZD1222 and BNT162b2 vaccines accounting for 52% and 38% of the recipients, respectively. To date, 43 million people have received the second dose of the vaccine (January 2022), of which AZD1222 accounts for 25% and BNT162b2 accounts for 55% (https://ncv.kdca.go.kr, accessed on 31 January 2022).

Serious vaccine-related effects, including thrombotic thrombocytopenia, cerebral venous sinus thrombosis, splanchnic vein thrombosis, and pulmonary embolism, were reported after vaccination for COVID-19 [2,3,4,5,6]. In terms of ophthalmic reaction to COVID-19 vaccination, various manifestations including eyelid swelling, ptosis, superior ophthalmic vein thrombosis, acute graft rejection after keratoplasty, cranial nerve palsy, retinal vein occlusion, submacular hemorrhage, scleritis, uveitis, acute macular neuroretinopathy, optic neuritis, and paracentral acute middle maculopathy were found in several cases [7,8,9,10,11,12,13]. The COVID-19 vaccines with reported ophthalmic reactions included the mRNA vaccine (BNT162b2, Pfizer, Brooklyn, NY, USA; mRNA-1273, Moderna, Cambridge, MA, USA), vector vaccine (Ad26COVS1, Janssen Johnson & Johnson, New Brunswick, NJ, USA; AZD1222, Oxford–AstraZeneca, Cambridge, UK), and whole virus (PiCoVacc, Sinovac Biotech, Beijing, China; BBIBP-CorV, Sinopharm, Beijing, China) [14,15]. However, the causal relationship and the mechanisms by which these conditions develop remain unclear. Here, we present one of the largest reports of 17 cases with acute and severe ocular adverse events seemingly temporally related to COVID-19 vaccination that occurred following COVID-19 vaccination in a single center.

Go to:

2. Materials and Methods

This single-center, retrospective observational case series adhered to the tenets of the Declaration of Helsinki and received approval from the Institutional Review Board of the Korea University Medical Center (IRB no. 2021GR0402). Given the retrospective nature of the study, the institutional review board of the Korea University Medical Center waived the need for informed patient consent. We included patients who experienced ophthalmic symptoms and were diagnosed with a new ophthalmic disease or exacerbation of a previously diagnosed ophthalmic disease following vaccination for COVID-19, from March 2021 to January 2022, at Korea University Guru Hospital in Seoul, Korea. Only patients in whom these symptoms occurred within seven days after inoculation were included. We followed the reporting guidelines for case-series studies [16] and noted the limitations of an uncontrolled design; however, we highlighted the importance of prompt reporting in the field of COVID-19 because of the ongoing pandemic and drastic increase in the number of vaccinations.

Information on the patients’ age, sex, medical and ophthalmic history, diagnosis, visual acuity, and treatment was obtained. The visual acuity is presented with the Snellen scale. The name, dose, and administration date of the vaccine were also obtained through detailed history-taking. All eyes with retinal disorder and uveitis underwent ultra-wide-field fundus photography using a fundus camera (Optos Inc., Dunfermline, UK) and spectral-domain optical coherence tomography (OCT; Spectralis OCT; Heidelberg Engineering, Heidelberg, Germany). Eyes with retinal vein or artery occlusion and posterior uveitis were subjected to fluorescein angiography (FA) using a Spectralis HRA+OCT device (Heidelberg Engineering, Heidelberg, Germany). Angle-closure glaucoma (ACG) patients underwent examinations including axial length (AL) (IOL Master, Carl Zeiss Meditec, Dublin, CA), and central corneal thickness (SP-2000P specular microscope Topcon Medical Systems, Tokyo, Japan) measurements along with intraocular pressure (IOP) measurement using Goldmann applanation tonometry, anterior segment optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Jena, Germany), and 24-2 Swedish interactive threshold algorithm standard automated perimetry (Carl Zeiss Meditec, Jena, Germany). Ultrasound biomicroscopy (Model P60, Paradigm Medical Industries Inc., Salt Lake City, UT, USA) was performed in only one ACG patient. Laboratory tests, including complete blood count, prothrombin time, activated partial thromboplastin time, and comprehensive metabolic profiles were performed in 11 of 17 patients. In RVO patients, an anti-PF4 antibody assay was performed for possible cases (n = 4). The mean and standard deviation (mean ± SD) of the clinical parameters are presented.

Go to:

3. Results

Seventeen eyes of 16 patients were included in this study. Of the study participants, 12 patients (75%) had been vaccinated with the AstraZeneca vaccine (AZD1222, Cambridge, UK) and 4 (25%) with the Pfizer vaccine (BNT162b2, Pfizer, New York, NY, USA and BioNTech, Mainz, Germany). Table 1 summarizes the characteristics of the patients in this report. All patients in this case series were Asian. The mean age at symptom presentation was 63.8 ± 11.9 (range 33–83) years. RVO was most commonly observed (nine eyes, 52.9%); branch retinal artery occlusion was observed in one eye (5.9%). Among the three uveitis patients (17.6%), one eye had no history of uveitis but presented with anterior uveitis after vaccination; two eyes had a controlled panuveitis history and showed worsening of panuveitis after vaccination. In four eyes (23.5%), an angle-closure attack that did not improve with glaucoma eyedrops and laser iridotomy was observed. All patients visited our clinic complaining of decreased visual acuity and ocular pain was observed in ACG patients, and visual symptoms occurred at an average of 3.5 ± 2.3 (1–7) days after inoculation.

Table 1

Case presentations.

CaseAgeSexVaccinationDose of VaccinationLateralitySymptom Onset aVA (Snellen)VA before Vaccination
(If Known)
DiagnosisSystemic
Underlying Disease
Ophthalmic Underlying Disease
(Year of Diagnosis)
Previous Medication
(s)
Treatment
164MAZD12221RE120/25CRVONoneNoneNoneObservation with aspirin
233FBNT162b22RE620/40CRVONoneNoneNoneAnti-VEGF injection
348MBNT162b23RE620/125CRVONoneNoneNoneAnti-VEGF injection
469FAZD12221LE320/20BRVONoneNoneNoneObservation with aspirin
566MAZD12222LE720/2020/20BRVONoneNoneNoneObservation
668FAZD12221RE1Hand motionBRVO with vitreous hemorrhageNoneBRVO (2020)AspirinObservation
774FAZD12222RE6Hand motion20/25BRVO with vitreous hemorrhageHTN, Nasal cavity cancer (CTx. Complete remission–2016’)BRVO (2020)AspirinVitrectomy
8 (the other eye of case #7)74FAZD12222RE6Hand motionHand motionBRVO with vitreous hemorrhageHTN, Nasal cavity cancer (CTx. Complete remission–2016’)BRVO (2020)AspirinVitrectomy
963FAZD12221LE320/63020/630CRVO decompensationNoneCRVO (2021)NoneAnti-VEGF injection
1062MAZD12221LE120/6320/25BRAOHTN, DM, Cerebral infarction (2017’)ERM Secondary glaucomaClopidogrelObservation
1162MAZD12221RE120/10020/40Uveitis exacerbationHTNControlled panuveitisPO steroid
PO cyclosporine
Steroid b
PO methotrexate
1279FBNT162b21RE320/20020/63Uveitis exacerbationDM, AsthmaControlled panuveitisNoneSteroid b
PO methotrexate
1355FBNT162b23RE220/5020/25Anterior uveitisHTNBRVO (2019)NoneSteroid b
1471FAZD12221LE620/50ACG attackHTNNoneNonePhaco with goniosynechiolysis
1583FAZD12221RE3Counting fingerACG attackNoneNoneNoneTrabeculectomy c
1659FAZD12221RE120/10020/25ACG attackHTNACG (2021)Dorzolamide and timolol eyedropPhaco d
1764MAZD12222RE620/50ACG with Lens displacementNoneNoneNoneVitrectomy

Open in a separate window

a no. of days after vaccination. b Topical steroid, retrobulbar triamcinolone injection and per oral steroid. c Laser iridotomy and argon laser peripheral iridoplasty were failed to control IOP. d Laser iridotomy was tried but failed to control IOP. Abbreviations: RE, right eye; LE, left eye; VA, visual acuity; CRVO, central retinal vein occlusion; BRVO, branch retinal vein occlusion; BRAO, branch retinal artery occlusion; ERM, epiretinal membrane; ACG, angle-closure glaucoma; HTN, hypertension; DM, diabetes mellitus; PO, per oral; VEGF, vascular endothelial growth factor; Phaco, phacoemulsification.

3.1. RVO (Cases 1–9)

RVO was diagnosed in nine eyes of eight patients (three men and five women) by fundus examination and FA (Figure 1). The mean age at symptom presentation was 62.1 ± 13.4 years (range: 33–74 years). One patient who showed vitreous hemorrhage with branch RVO in both eyes had hypertension (12.5%), but other patients had no systemic disease. Six patients (75%) received the AZD1222 vaccine, and two (25%) received the BNT162b2 vaccine. Two patients with the Pfizer vaccine were 33 and 48 years old, respectively. Four patients (44.4%) experienced RVO after their first dose of vaccination, three (33.3%) after their second dose, and one (11.1%) after the third dose. Five patients (Cases # 1–5) showed newly developed RVO but demonstrated relatively preserved visual acuity (VA) (20/125 to 20/20), while four eyes of three patients (cases # 6–9) showed exacerbation of existing RVO and experienced significant vision loss due to dense vitreous hemorrhage and macular edema (VA hand motion to 20/630). The three eyes of cases #6–8 had a history of vitrectomy due to vitreous hemorrhage which accompanied the RVO. The mean time between vaccination and visual symptom development was 4.3 days (range: 1–7 days). Five eyes were treated with intravitreal bevacizumab injection (IVB), and one patient who showed vitreous hemorrhage in both eyes underwent vitrectomy because the vitreous hemorrhage was not resolved after IVB. The hematologic evaluation was performed in six patients, and anti-PF4 antibodies assay was performed in three patients, but no abnormal findings were observed.

An external file that holds a picture, illustration, etc.
Object name is jcm-11-03318-g001.jpg

Figure 1

(A) (Patient 1) A 64-year-old man, who had no previously diagnosed disease, visited our clinic complaining of reduced visual acuity (VA) in the right eye one day after AZD1222 inoculation. (Left) Severe vessel tortuosity with scattered blot retinal hemorrhage was observed during a fundus examination of the right eye. (Right upper) Early phase (arterial phase) delay and arterio-venous transit time were found during fluorescein angiography, indicating central retinal vein occlusion. (Right lower) Multiple focal leaks and disc hyperemia in the late phase were also observed. (B) (Patient 4) A 63-year-old woman was diagnosed with central retinal vein occlusion in her left eye in January 2021 at our hospital and underwent pan-retinal photocoagulation of the left eye and four intravitreal anti-vascular endothelial growth-factor injections. (Left) At her last visit just before vaccination, the retinal hemorrhage in the left eye was hardly visible, vessel tortuosity was not severe, and a focal intraretinal cyst was observed on OCT images. Additionally, her VA was 20/360. (Right) The patient reported that three days after AZD1222 vaccination, her vision had deteriorated, and her visual acuity as measured at the outpatient clinic was 20/360. It was confirmed via fundus examination that the vessel tortuosity was also greatly increased, and there was macular edema present on OCT images. (C,D) (Patient 5) A 62-year-old man visited the hospital complaining that one-third of his visual field in the left eye was blurred (VA 20/63) one day after AZD1222 vaccination. (C) During fundus examination, retinal whitish ischemic changes at the superotemporal arcade were observed, and inner retinal swelling due to acute ischemia was confirmed on OCT images. (D) During the FA examination, a filling delay in the superior retinal arteries in the early phase was observed, and in the wide FA photograph, non-perfusion of the relevant area was observed in the late phase. Notably, both eyes had mild vascular leaks, suggesting vasculitis.

3.2. Retinal Artery Occlusion (Case 10)

A 62-year-old man, who had received the first dose of the AZD1222 vaccine one day prior to presentation, complained of a central visual field defect and reduced VA (20/63). He had hypertension, diabetes, and a history of cerebral infarction in 2017. Fundus examination revealed retinal whitish ischemic changes at the super temporal arcade on OCT images (Figure 1C). A filling delay in the superior retinal arteries in the early phase was observed in the FA examination, and both eyes had mild vascular leaks in the late phase, suggesting vasculitis. (Figure 1D). No abnormal finding was observed in the hematologic evaluation.

3.3. Uveitis (Cases 11–13)

Cases 11 and 12 were of patients with a history of panuveitis accompanied by vasculitis as an underlying disease (Figure 2A,B). Patient 11 was positive for human leukocyte antigen B51 at the time of diagnosis of panuveitis, and steroid and cyclosporine were orally administered, while patient 12 was in a stable state without the need for medication. These patients were inoculated with the AZD1222 vaccine and BNT162b2 vaccine, respectively, and both visited the clinic due to reduced VA after one and three days, respectively. In both cases, greater vitreous opacity, keratic precipitates, and an increase in the number of inflammatory cells in the anterior chamber were observed. Both cases were followed up until recently (May 2022). Case #11 received three intravitreal triamcinolone injections for macular edema and phacoemulsification for the cataract. PO cyclosporin and methotrexate were maintained. The patient showed well-controlled inflammation with a final visual acuity of 20/40. Case #12 received retrobulbar triamcinolone injections twice for macular edema. Moreover, PO methotrexate was added to control inflammation. Her final visual acuity was 20/60. Case 13 was of a 55-year-old woman, who had hypertension and a history of branch RVO (in 2019) without other ophthalmic complications. The woman presented with anterior uveitis showing keratic precipitate and inflammatory cells in the anterior chamber two days after the third dose of the BNT162b2 vaccine. In FA, there were no signs of vasculitis or retinal or choroidal inflammation. The anterior uveitis was well controlled by topical steroids without recurrence. The hematologic evaluation in three patients showed no abnormal finding.

An external file that holds a picture, illustration, etc.
Object name is jcm-11-03318-g002.jpg

Figure 2

(A) (Patient 11) A 62-year-old man, previously diagnosed with panuveitis with human leukocyte antigen B51 positivity and who was taking an oral steroid and cyclosporin (Left), shows well-controlled uveitis, although vitreous opacity remains (visual acuity 20/40). (Right) The patient reported a decrease in visual acuity (VA) in the right eye one day after AZD1222 inoculation, documented as 20/100. An increase in vitreous opacity in the right eye was confirmed during fundus examination, and keratic precipitates and inflammatory cells in the anterior chamber during the slit-lamp examination were observed. (B) (Patient 12) The disease of a 79-year-old woman, who was diagnosed with panuveitis 20 years prior and undergoing follow-up, was well-controlled without topical and systemic medications (right eye VA 20/63). (Left) A relatively clear vitreous without signs of inflammation during fundus examination was observed at the last visit. (Right) The patient was inoculated with BNT162b2, and three days later, she complained of decreased VA in the right eye (20/200) and stiff pain in both eyes. During fundus examination, vitreous opacity and focal retinal infiltration were observed in her right eye.

3.4. Primary Angle-Closure (Cases 14–17)

Four patients visited the clinic following AZD1222 vaccination with ocular pain and significant acute visual loss, displaying corneal microscopic cystic edema with conjunctival injection, a shallow central anterior chamber, and peripheral anterior chamber collapse nearly touching the cornea with a phakic eye (Figure 3A,B). Our four subjects’ anterior chamber depths (ACDs) were 2.19 mm, 2.19 mm, 2.89 mm, and 2.31 mm, respectively. Their axial lengths were 21.84 mm, 22.95 mm, 22.37 mm, and 23.71 mm, respectively. All four patients presented high IOP values (36, 66, 70, and 34 mmHg) and traced to one positive anterior chamber cell reaction in attacked eyes. Their spherical equivalents (SE, right eye/left eye) were −1.1/−3.63 diopters, −2.6/−3.75 D, −2.25/+1.15 D, and +0.5/+2.86 on the initial visit day after an attack, respectively. Case #16 had visited our clinic 2 weeks before the ACG attack for meibomian gland dysfunction. Hence, we were able to compare her refraction at the time of the ACG attack relative to the previous record. The SE of her right eye was −0.89 diopters at 2 weeks before the ACG attack and −2.25 diopters on the day of the ACG attack. The patient demonstrated myopic shift from her prior measurement. For IOP control, case #14 underwent phacoemulsification with goniosynechiolysis because her gonioscopic exam represented a 360° peripheral anterior synechia (PAS). Case #15 underwent trabeculectomy with Argon laser peripheral iridoplasty. The laser iridotomy did not achieve satisfactory IOL lowering effects. Case #17 had phacoemulsification with posterior chamber lens implantation. In Case #18, we decided to perform a vitrectomy with IOL scleral fixation, as his lens showed anterior shift with phacodonesis due to zonule laxity. All four cases showed generally good prognosis in terms of intraocular pressure and final visual acuity (20/20, 20/100, 20/20, and 20/25). All patients were free of corneal complications except case #15, who demonstrated a decreased corneal endothelial cell count before trabeculectomy. The patient recovered a clear cornea after surgery without edema.

An external file that holds a picture, illustration, etc.
Object name is jcm-11-03318-g003.jpg

Figure 3

(Patient 14) A 71-year-old woman with hypertension presented to the emergency department with a two-day history of pain and redness in the left eye (visual acuity 20/50). (A) An ophthalmic examination revealed a high IOP of 36 mmHg associated with shallowing of the anterior chamber peripherally in the left eye. (B) Anterior-segment OCT images show anterior bowing of the peripheral iris and closing of the iridocorneal angle in the left eye. Her axial length was 21.86 mm in the right eye and 21.84 mm in the left eye, and her spherical equivalents were −1.13 and −3.63 diopters, respectively. An acute attack of angle closure was diagnosed, and treatment with laser peripheral iridotomy was attempted but failed. The next day, phacoemulsification with goniosynechialysis was performed and her IOP dropped to 7 mmHg.

Go to:

4. Discussion

Herein, we report a case series of acute ocular adverse events related to COVID-19 vaccination. Our ophthalmic clinic is a tertiary hospital located in the Guro district in Seoul. We care for approximately 60,000 people in the outpatient department annually. Among a total of 393,822 people in Guro district, 333,958 have received the first vaccination dose and 43,214 have received the second vaccination dose, based on our community’s Public Health Service announcement). Our clinic is a tertiary hospital. Patients from other districts are referred to us. Hence, determining the prevalence was challenging. As this was a retrospective study analyzing patient medical records, there were certain limitations to definitively confirming a causal relationship between such immunization and the noted ocular manifestations. Furthermore, laboratory and anti-PF4 antibody tests were performed only in some patients, and those who were tested showed negative results. Laboratory tests cannot prove a correlation between ocular adverse events and the vaccination; however, we only included patients who showed acute ocular symptoms within one week of vaccination to determine the temporal association of COVID-19 vaccination and ocular adverse events.

In this study, we presented a large case-series of ocular adverse events after COVID-19 vaccination, including nine RVO cases, one retinal artery occlusion case, three uveitis cases, and four cases of acute angle closure, which has not been reported previously. In the cases of RVO, which was the most common ophthalmic manifestation in this report, only one of eight patients (12.5%) had hypertension, which was much lower than that in a previous report of RVO cases among Koreans (48.2%) [17]. The cases with vitreous hemorrhage (cases #6~8) had a history of vitrectomy due to vitreous hemorrhage which accompanied the RVO, meaning that there was previous neovascularization. Park et al. reported on submacular hemorrhage and vitreous hemorrhage in a patient with age-related macular degeneration and RVO [7]. The vessel vulnerable to microvascular dysfunction including neovascularization due to AMD and RVO may develop hemorrhagic complications after COVID-19 vaccination.

The AZD1222 vaccine is an adenovirus vector vaccine containing the coding region for the severe acute respiratory coronavirus disease 2 (SARS-CoV-2) spike protein gene, which triggers a strong innate inflammatory response [18]. Conversely, the BNT162b2 is a lipid nanoparticle formulated nucleoside-modified RNA encoding the SARS-CoV-2 full-length spike protein [19]. Spike proteins produced by adenovirus-vectored vaccination mimic the SARS-CoV-2 spike protein’s receptor binding structure [20]. SARS-CoV-2 uses the spike protein to invade cells by attaching to angiotensin-converting enzyme 2 receptor (ACE2) as the target receptor. The interactions between ACE2 and free-floating spike proteins enhance the overactivity of angiotensin II, which may help to trigger inflammation, thrombosis, and other adverse reactions [18]. A previous analysis of fundus photography of patients with COVID-19 revealed increased artery and vein diameters and tortuosity [21], while another OCT angiography analysis documented reduced vessel density with and without thromboembolism [22], supporting the findings of retinal vascular inflammation in COVID-19 patients. Although there are no reports on the effects of COVID-19 vaccines on the retinal artery and vein, inflammation in the retinal vessels caused by adenoviral vector vaccines and spike proteins can be predicted along with vein compression or microthromboembolic events due to increased vessel tortuosity and arterial vessel dilation.

Vaccination can induce all types of uveitis, albeit mainly transient anterior uveitis and sometimes vasculitis, as well as panuveitis [23]. The incidence of uveitis after general vaccination was reported to range from 8 to 13 per 100,000 persons/year [24]. Mudie et al. assumed some possible causes of this rare type of uveitis [10]. One is molecular mimicry between the vaccine and ocular structures driving the adaptive immune system to induce autoimmunity. The self-reactive immune system may cause uveitis as well [25]. Another hypothesis is that an enhancement of the systemic innate immune system results in significant cytokine activation. The exacerbation and new development of uveitis in patients 11 and 12 might be due to innate and adaptive immune reactions to the vaccine, although molecular mimicry between the vaccine and ocular structure is another possibility [10].

Further, we hypothesized the main etiology of the four angle-closure attack cases following COVID-19 vaccination is ciliary body swelling due to uveitis. Not all patients were photographed, and Ultrasound biomicroscopy figures were available in one case in our study. Figure 4 shows swelling of the ciliary body six days after vaccination that led to zonule laxity accompanied by phacodonesis, causing a closed-angle attack. The swollen ciliary body may lead to anterior shifting of the lens and, consequently, to a myopic shift. Although we only compared SE before and after the ACG attack in case #16, the other cases were more likely to have myopic SE in the affected eyes than the fellow eye. The median age of our four ACG patients was 69.5 years, and the women to men ratio was 3:1, similar to that in a multi-centered Korean study with an average age of 64.28 years and sex ratio of 3.13:1 [26]. Axial lengths of our ACG subjects were 21.84 mm, 22.95 mm, 22.37 mm, and 23.71 mm, which were similar with average 22.42 mm in one of acute primary angle-closure studies in Korea [27]. Conversely, our subjects’ anterior chamber depths (ACDs) were 2.19 mm, 2.19 mm, 2.89 mm, and 2.31 mm, which were deeper than the average ACDs in ACG cases in Korea (1.87 mm) in 2017 [27].

An external file that holds a picture, illustration, etc.
Object name is jcm-11-03318-g004.jpg

Figure 4

(Patient 17) (A) Right eye of a 64-year-old man, who had no previously diagnosed disease. He visited our clinic complaining of pain and redness in the right eye 6 days after AZD1222 inoculation. (B) His left eye shows a normal peripheral angle and no zonule laxity. His initial IOP was 34 mmHg associated with shallowing of the anterior chamber peripherally in the right eye. His bio-microscopy images show anterior bowing of the peripheral iris and ciliary swelling in the right eye than the left eye, which caused phacodonesis of the right eye and closure of the iridocorneal angle in the right eye. An acute attack of angle closure was diagnosed, treatment with laser peripheral iridotomy was attempted, and his IOP dropped to 10 mmHg.

Moreover, hypersecretion of aqueous humor may be a contributing factor. The renin-angiotensin system has been identified in the human ciliary body and aqueous humor, and angiotensin II acts as a secretagogue in human ciliary non-pigmented epithelial cells [28]. The loss of ACE2 due to interactions between spike proteins produced by COVID-19 vaccination may lead to the overactivity of angiotensin II [18] and its increase in the aqueous humor. Even considering the high prevalence of ACG in Asia, this mechanism would be worth considering when treating patients with ACG following COVID-19 vaccination [29].

AZD1222 and BNT162b2 were administered to different populations in accordance with government guidelines. AZD1222 was mainly inoculated in older individuals, and the age limit was changed from over 30 years to over 50 years during the study period. However, BNT162b2 vaccine was inoculated in individuals over 16 years of age without an upper age limit. Therefore, it is impossible to compare adverse events between the two vaccines, and it is considered that relatively more ocular adverse events were reported with AZD1222, which had an older inoculation age. Some of the patients included in this report had an underlying disease, and although the possibility of coincidental ophthalmic manifestation due to the underlying disease cannot be excluded, since a large number of cases of ocular adverse events were noted in a single-center study in a limited period, a temporal association between vaccination for COVID-19 and ophthalmic disorders is more likely.

Ocular manifestations in patients infected with COVID-19 have been reported. Most were mild, such as conjunctival congestion, conjunctivitis, dry eye, and keratitis [30]. Case reports of retinal and choroidal manifestations after COVID-19 injection have highlighted retinal microvascular changes including cotton wool spot, intraretinal hemorrhages, paracentral acute middle maculopathy, acute macular neuroretinopathy, retinal vein occlusion, and uveitis [31]. Although the mechanism of these ocular manifestations has not been clearly elucidated, the presence of SARS-CoV-2 in the vitreous and retina of patients with COVID-19 [32] may implicate the viral infection directly or contribute to immune-mediated inflammation. The ophthalmic complications after COVID-19 infection are similar to the adverse events after COVID-19 vaccination.

This was a single-center retrospective review, and no incidence analysis was performed. In addition, there is no appropriate control group, and since it was not a survey of patients who had been vaccinated in a single center, only observational reports could be included. This study only included severe ocular adverse events that affected visual acuity. Other ophthalmic events, such as eyelid swelling, ptosis, and cranial nerve palsy that were previously reported may not have been considered. Furthermore, systemic evaluations were not conducted uniformly in all cases. Population-based studies with national health insurance records for the evaluation of the incidence of ocular adverse events before and after COVID-19 vaccination may help determine the correlation.

Because of the absence of a prevalence analysis, the causality and direct correlation between ocular reactions and COVID-19 vaccination cannot be determined from this report. However, the possibility of a temporal association between the reported ophthalmic manifestations and COVID-19 vaccination provides a new perspective. Although prevalence assessment was not conducted, the strength of our study was its homogeneity, as only Asians were included. The reported ophthalmic events were unexpected. Ocular adverse events are relatively rare, and the benefits of vaccination outweigh the risks if appropriate ophthalmic management is followed. Adopting an enhanced watchfulness protocol, especially for the at-risk patients—including recipients of corneal grafts, and those with a history of uveitis and retinal vascular disease—may be necessary after COVID-19 vaccination.

Go to:

5. Conclusions

Clinicians should consider the effect of COVID-19 vaccination on ophthalmic disease. Further studies are required to elucidate the possible effects of COVID-19 vaccination on the eye.

References

1. The Royal College of Ophthalmologists Safety Alert: Retinal Vein Occlusions Post COVID Vaccination. [(accessed on 13 May 2021)]. Available online: https://www.rcophth.ac.uk/news-views/safety-alert-retinal-vein-occlusions-post-covid-vaccination/

2. Bayas A., Menacher M., Christ M., Behrens L., Rank A., Naumann M. Bilateral superior ophthalmic vein thrombosis, ischaemic stroke, and immune thrombocytopenia after ChAdOx1 nCoV-19 vaccination. Lancet. 2021;397:e11. doi: 10.1016/S0140-6736(21)00872-2. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

3. Greinacher A., Thiele T., Warkentin T.E., Weisser K., Kyrle P.A., Eichinger S. Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination. N. Engl. J. Med. 2021;384:2092–2101. doi: 10.1056/NEJMoa2104840. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

4. Guetl K., Gary T., Raggam R.B., Schmid J., Wölfler A., Brodmann M. SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia treated with immunoglobulin and argatroban. Lancet. 2021;397:e19. doi: 10.1016/S0140-6736(21)01238-1. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

5. Schultz N.H., Sørvoll I.H., Michelsen A.E., Munthe L.A., Lund-Johansen F., Ahlen M.T., Wiedmann M., Aamodt A., Skattør T.H., Tjønnfjord G.E., et al. Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination. N. Engl. J. Med. 2021;384:2124–2130. doi: 10.1056/NEJMoa2104882. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

6. Von Hundelshausen P., Lorenz R., Siess W., Weber C. Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT): Targeting Pathomechanisms with Bruton Tyrosine Kinase Inhibitors. Thromb. Haemost. 2021;121:1395–1399. doi: 10.1055/a-1481-3039. [PubMed] [CrossRef] [Google Scholar]

7. Park H.S., Byun Y., Byeon S.H., Kim S.S., Kim Y.J., Lee C.S. Retinal Hemorrhage after SARS-CoV-2 Vaccination. J. Clin. Med. 2021;10:5705. doi: 10.3390/jcm10235705. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

8. Pichi F., Aljneibi S., Neri P., Hay S., Dackiw C., Ghazi N.G. Association of Ocular Adverse Events with Inactivated COVID-19 Vaccination in Patients in Abu Dhabi. JAMA Ophthalmol. 2021;139:1131–1135. doi: 10.1001/jamaophthalmol.2021.3477. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

9. Bolletta E., Iannetta D., Mastrofilippo V., de Simone L., Gozzi F., Croci S., Bonacini M., Belloni L., Zerbini A., Adani A., et al. Uveitis and Other Ocular Complications Following COVID-19 Vaccination. J. Clin. Med. 2021;10:5960. doi: 10.3390/jcm10245960. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

10. Mudie L.I., Zick J.D., Dacey M.S., Palestine A.G. Panuveitis following Vaccination for COVID-19. Ocul. Immunol. Inflamm. 2021;29:741–742. doi: 10.1080/09273948.2021.1949478. [PubMed] [CrossRef] [Google Scholar]

11. Bøhler A.D., Strøm M.E., Sandvig K.U., Moe M.C., Jørstad Ø.K. Acute macular neuroretinopathy following COVID-19 vaccination. Eye. 2022;36:644–645. doi: 10.1038/s41433-021-01610-1. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

12. Book B.A.J., Schmidt B., Foerster A.M.H. Bilateral Acute Macular Neuroretinopathy After Vaccination Against SARS-CoV-2. JAMA Ophthalmol. 2021;139:e212471. doi: 10.1001/jamaophthalmol.2021.2471. [PubMed] [CrossRef] [Google Scholar]

13. Mambretti M., Huemer J., Torregrossa G., Ullrich M., Findl O., Casalino G. Acute Macular Neuroretinopathy following Coronavirus Disease 2019 Vaccination. Ocul. Immunol. Inflamm. 2021;29:730–733. doi: 10.1080/09273948.2021.1946567. [PubMed] [CrossRef] [Google Scholar]

14. Haseeb A.A., Solyman O., Abushanab M.M., Abo Obaia A.S., Elhusseiny A.M. Ocular Complications Following Vaccination for COVID-19: A One-Year Retrospective. Vaccines. 2022;10:342. doi: 10.3390/vaccines10020342. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

15. Ng X.L., Betzler B.K., Ng S., Chee S.P., Rajamani L., Singhal A., Rousselot A., Pavesio C.E., Gupta V., de Smet M.D., et al. The Eye of the Storm: COVID-19 Vaccination and the Eye. Ophthalmol. Ther. 2022;11:81–100. doi: 10.1007/s40123-021-00415-5. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

16. Kempen J.H. Appropriate use and reporting of uncontrolled case series in the medical literature. Am. J. Ophthalmol. 2011;151:7–10.e11. doi: 10.1016/j.ajo.2010.08.047. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

17. Lee J.Y., Yoon Y.H., Kim H.K., Yoon H.S., Kang S.W., Kim J., Park K.H., Jo Y.J. Baseline characteristics and risk factors of retinal vein occlusion: A study by the Korean RVO Study Group. J. Korean Med. Sci. 2013;28:136–144. doi: 10.3346/jkms.2013.28.1.136. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

18. Angeli F., Spanevello A., Reboldi G., Visca D., Verdecchia P. SARS-CoV-2 vaccines: Lights and shadows. Eur. J. Intern. Med. 2021;88:1–8. doi: 10.1016/j.ejim.2021.04.019. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

19. Polack F.P., Thomas S.J., Kitchin N., Absalon J., Gurtman A., Lockhart S., Perez J.L., Marc G.P., Moreira E.D., Zerbini C., et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N. Engl. J. Med. 2020;383:2603–2615. doi: 10.1056/NEJMoa2034577. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

20. Watanabe Y., Mendonça L., Allen E.R., Howe A., Lee M., Allen J.D., Chawla H., Pulido D., Donnellan F., Davies H., et al. Native-like SARS-CoV-2 Spike Glycoprotein Expressed by ChAdOx1 nCoV-19/AZD1222 Vaccine. ACS Cent. Sci. 2021;7:594–602. doi: 10.1021/acscentsci.1c00080. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

21. Invernizzi A., Torre A., Parrulli S., Zicarelli F., Schiuma M., C olombo V., Giacomelli A., Cigad M., Milazzo L., Ridolfo A., et al. Retinal findings in patients with COVID-19: Results from the SERPICO-19 study. EClinicalMedicine. 2020;27:100550. doi: 10.1016/j.eclinm.2020.100550. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

22. Guemes-Villahoz N., Burgos-Blasco B., Vidal-Villegas B., Donate-López J., de la Muela M.H., López-Guajardo L., Martín-Sánchez F.J., García-Feijoó J. Reduced macular vessel density in COVID-19 patients with and without associated thrombotic events using optical coherence tomography angiography. Graefe’s Arch. Clin. Exp. Ophthalmol. 2021;259:2243–2249. doi: 10.1007/s00417-021-05186-0. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

23. Agarwal M., Dutta Majumder P., Babu K., Konana V.K., Goyal M., Touhami S., Stanescu-Segall D., Bodaghi B. Drug-induced uveitis: A review. Indian J. Ophthalmol. 2020;68:1799–1807. doi: 10.4103/ijo.IJO_816_20. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

24. Klein N.P., Ray P., Carpenter D., Hansen J., Lewis E., Fireman B., Black S., Galindo C., Schmidt J., Baxter R. Rates of autoimmune diseases in Kaiser Permanente for use in vaccine adverse event safety studies. Vaccine. 2010;28:1062–1068. doi: 10.1016/j.vaccine.2009.10.115. [PubMed] [CrossRef] [Google Scholar]

25. Cunningham E.T., Jr., Moorthy R.S., Fraunfelder F.W., Zierhut M. Vaccine-Associated Uveitis. Ocul. Immunol. Inflamm. 2019;27:517–520. doi: 10.1080/09273948.2019.1626188. [PubMed] [CrossRef] [Google Scholar]

26. Hong C., Hong S.W., Park C.K., Sung K.R., Kim C.S. Profiles and Clinical Characteristics of Newly Diagnosed Glaucoma in Urban Korea: A Multicenter Study. Korean J. Ophthalmol. 2020;34:353–360. doi: 10.3341/kjo.2020.0033. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

27. Ha J.Y., Sung M.S., Heo H., Park S.W. Trends in the characteristics of acute primary angle closure in Korea over the past 10-years. PLoS ONE. 2019;14:e0223527. doi: 10.1371/journal.pone.0223527. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

28. Cullinane A.B., Leung P.S., Ortego J., Coca-Prados M., Harvey B.J. Renin-angiotensin system expression and secretory function in cultured human ciliary body non-pigmented epithelium. Br. J. Ophthalmol. 2002;86:676–683. doi: 10.1136/bjo.86.6.676. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

29. Soh Z.D., Thakur S., Majithia S., Nongpiur M.E., Cheng C.Y. Iris and its relevance to angle closure disease: A review. Br. J. Ophthalmol. 2021;105:3–8. doi: 10.1136/bjophthalmol-2020-316075. [PubMed] [CrossRef] [Google Scholar]

30. Chen L., Deng C., Chen X., Zhang X., Chen B., Yu H., Qin Y., Xiao K., Zhang H., Sun X. Ocular manifestations and clinical characteristics of 535 cases of COVID-19 in Wuhan, China: A cross-sectional study. Acta Ophthalmol. 2020;98:e951–e959. doi: 10.1111/aos.14472. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

31. Zhang Y., Stewart J.M. Retinal and choroidal manifestations of COVID-19. Curr. Opin. Ophthalmol. 2021;32:536–540. doi: 10.1097/ICU.0000000000000801. [PubMed] [CrossRef] [Google Scholar]

32. Casagrande M., Fitzek A., Püschel K., Aleshcheva G., Schultheiss H., Berneking L. Detection of SARS-CoV-2 in Human Retinal Biopsies of Deceased COVID-19 Patients. Ocul. Immunol. Inflamm. 2020;28:721–725. doi: 10.1080/09273948.2020.1770301. [PubMed] [CrossRef] [Google Scholar]

Ophthalmology Overview: COVID-19 Infection in Eye Cells, Vision Loss and Blindness Prevalence, and More

Authors: AJMC Staff

Highlighting the latest ophthalmology-related news reported across MJH Life Sciences™.Highlighting the latest ophthalmology-related news reported across MJH Life Sciences.

Mount Sinai Study Finds COVID-19 Can Infect Eye Cells

Although aerosol transmission is considered the primary cause of COVID-19 infection, findings from a study published this week by researchers at Mount Sinai indicates that the virus may also be transmitted through the eye, with the limbus especially susceptible.

As reported by Ophthalmology Times®, implications of COVID-19 on ocular manifestations have been seen with a previous study suggesting that the virus can cause conjunctivitis, or pink eye, along with epiphora and chemosis. The researchers of the present study sought to delve further into quantifying the entry factor of the virus and antigen expression in postmortem patients who had COVID-19.

Examining adult human eye donor cells obtained via autopsy of patients who had COVID-19. in an in vitro stem cell model, analysis via RNA sequencing confirmed that the virus infected the ocular surface cells, with the protein associated with infection, ACE2, and an enzyme that facilitates viral entry, TMPRSS2, also identified.

Assessing US Prevalence of Visual Acuity Loss, Blindness

Reported by Ophthalmology Times®, a study published last week in JAMA Ophthalmology indicates that more than 7 million people in the United States are living with uncorrectable vision loss, including more than 1 million cases of blindness.

Identifying cases across all age groups, people younger than 40 years accounted for nearly 1 in 4 cases of vision loss or blindness, with 1.6 million cases overall and 141,000 cases of blindness—13% of all people with blindness in the United States.

Notably, the estimated number of cases is a 68% increase over the previous estimate created by the 2012 Vision Problems in the US study. In delineating at-risk populations, a higher risk of vision loss was found in Hispanic/Latino and Black individuals than among White individuals, with more females than males experiencing permanent vision loss or blindness.

Inherited Retinal Disease Awareness, Benefits of Genetic Testing

This week, Prevent Blindness is holding its second annual Inherited Retinal Disease (IRD) Genetic Testing Week, in which the nonprofit is posting educational content related to IRD, a unit of diseases that can lead to severe vision loss or blindness.

Affecting patients of all ages, an article by Modern Retina highlights that because many IRD conditions are degenerative, genetic testing may help identify treatment options early in the process. Moreover, due to the retina’s physical makeup, patients with IRD are strong candidates for gene therapy treatments that can help control disease progression, particularly in at-risk children and infants.

Providing a free fact sheet on IRD, the Prevent Blindness website also lists causes, risk factors, research and therapy options, financial assistance services, and more.

Acute Vision Loss in a Patient with COVID-19

Authors: Vijairam Selvaraj 1Daniel Sacchetti 2Arkadiy Finn 1Kwame Dapaah-Afriyie 1

Case Reports R I Med J (2013)  2020 Jun 10;103(6):37-38. NCBI

To date, there have been reports of neurologic manifestations in COVID-19 patients including ischemic strokes, Guillain-Barre Syndrome and anosmia. In this case report, we describe a patient who presented with dysosmia, dysgeusia, along with monocular peripheral vision loss after being diagnosed with COVID-19.

ABSTRACT
To date, there have been reports of neurologic manifestations in COVID-19 patients including ischemic strokes, Guillain-Barre Syndrome and anosmia. In this case report, we describe a patient who presented with dysosmia, dysgeusia, along with monocular peripheral vision loss after being diagnosed with COVID-19. neurologic, ophthalmology


INTRODUCTION
As of June 6, 2020, there are more than 6,500,000 cases of SARS-CoV-2 worldwide.1
To date, there have been several reports of neurologic manifestations in these patients including ischemic strokes, Guillain-Barre Syndrome and anosmia.2-4 Wu et al described a case series involving 38 patients with COVID-19, where 12 patients had ocular signs of epiphora, conjunctival congestion and chemosis.5 We report a patient who presented with dysosmia, dysgeusia along with monocular peripheral vision loss after being diagnosed with COVID-19.
CASE PRESENTATION
A woman in her 50s with a history of hypertension, hyperlipidemia, and headaches presented to the hospital with fever, chills, and cough one week after she tested positive for SARS-CoV-2. She reported acute, painless right eye monocular visual disturbance, described as a white cloud and blurriness involving most of her right eye, sparing the superior nasal aspect. She denied any left eye visual disturbances. She
denied any other ocular symptoms such as flashers, floaters, or diplopia. She denied any jaw claudication, scalp tenderness, unintentional weight loss. Other neurological symptoms included dysgeusia, dysosmia, right ear hypoascusis and subjective right hemiparesis. She was not taking any medications at home. On the day of admission, her neurological exam was remarkable for severe right eye vision loss. She was unable
to visualize or count fingers in the right temporal field and inferior nasal field. The left eye exam was normal. Relative afferent pupillary defect was absent. There was no tenderness to the palpation of the temporal area. The following day, she reported fifty percent improvement in her vision. Her vision in the far periphery of the right eye was blurry but she was able to count fingers in all fields. Visual acuity was 20/70. The dilated fundoscopic exam was normal. Ocular pressures were normal. There was no evidence of optic disc edema, Hollenhorst plaque, retinal whitening. or hemorrhages. Her laboratory values were normal including CBC, BMP and ESR. Her CRP was 7, and d dimer was 206 ng/ml. LDL was elevated at 131. Initial MRI of the brain without gadolinium did not reveal any intraparenchymal or cranial nerve abnormalities, though it was notable for a partially empty sella turcica. MRI of the orbits, face, and neck with and without adolinium revealed no area of abnormal enhancement.The optic nerves, chiasm, and optic tracts appeared normal.CT angiography showed no significant carotid disease. Her vision spontaneously improved during her hospitalization and she was discharged home on aspirin and atorvastatin.She was advised to follow up in the Ophthalmology clinic in one month.
DISCUSSION
The clinical spectrum of illness due to COVID-19 continues to evolve. Acute vision loss is a medical emergency and can occur over a few seconds or minutes to a few days. Vision
may become blurry, cloudy, entirely or partially absent, or affected by flashes or floaters. Acute vision loss is usually painless but may also be associated with ocular pain, redness and headache. Most cases of visual loss can be diagnosed by history and physical examination alone.Common causes of acute vision loss include Central
Retinal Artery Occlusion, Central Retinal Vein Occlusion (CRVO), Retinal Detachment, Optic Neuropathy, and Inflammatory conditions such as Giant Cell Arteritis (GCA).
CRVO was unlikely due to the absence of retinal hemorrhages and cotton wool spots on the fundoscopic exam. Given the history of peripheral monocular vision loss, transient Branch Retinal Artery Occlusion (BRAO) was considered a possibility, although there was no evidence of retinal whitening or edema. Given her normal ophthalmologic exam, Posterior Ischemic Optic Neuropathy (PION) was considered to be more likely. There are three different types of PION: arteritic,

CASE REPORT
non-arteritic, and surgical. The capillary plexuses supplying the posterior part of the optic nerve are vulnerable to hypoperfusion and ischemia. Vision typically recovers if
circulation is restored before axonal death, as observed in our case. Arteritic PION is usually due to GCA, which was unlikely given normal ESR, CRP, and the absence of classic symptoms such as jaw claudication and scalp tenderness. Our patient likely had non-arteritic PION due to small vessel disease that is usually linked to systemic illness. Given the MRI evidence of a partially empty sella, idiopathic intracranial hypertension, or pseudotumor cerebri, was also considered a possibility for transient visual loss. She did not undergo a lumbar puncture to measure intrathecal pressure as her ocular symptoms had improved and she denied any headache symptoms. Previous strains of coronavirus seem to invade the CNS mostly through the hematogenous route but also can invade
through the cribriform plate and the conjunctiva.5,6 The pathophysiology in our case is unclear. One of the mechanisms could involve inflammation associated with COVID19 itself, although her CRP and ESR were normal.7 Another mechanism could be related to the thromboembolic phenomenon and occlusion of small capillaries feeding the optic
nerve, although our patient’s d dimer was normal. Magro et al showed that there might be a microvascular injury syndrome mediated by activation of complement pathways and an associated procoagulant state that may also be at play in these patients.8
Our patient’s symptoms were early in the course of her illness and could be useful in triaging patients. A thorough neurologic exam is essential in all patients diagnosed
with COVID-19. This case illuminates a broader spectrum of COVID-19-related symptomatology and emphasizes the need for clinicians to be aware of the various clinical manifestations associated with this infection. \References

  1. World Health Organization. Coronavirus Disease (COVID-19)
    Situation Report-137. Accessed: June 6, 2020. https://www.who.
    int/emergencies/diseases/novel-coronavirus-2019/situationreports
  2. Oxley TJ, Mocco J, Majidi S, et al. Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young. N Engl J Med. 2020;
    382(20):e60.
  3. Toscano G, Palmerini F, Ravaglia S, et al. Guillain-Barré Syndrome Associated with SARS-CoV-2 [published online ahead of
    print, 2020 Apr 17]. N Engl J Med. 2020.
  4. Eliezer M, Hautefort C, Hamel A, et al. Sudden and Complete
    Olfactory Loss Function as a Possible Symptom of COVID-19.
    JAMA Otolaryngol Head Neck Surg. Published online April 08,
    2020.
  5. Wu P, Duan F, Luo C, et al. Characteristics of Ocular Findings of
    Patients With Coronavirus Disease 2019 (COVID-19) in Hubei
    Province, China. JAMA Ophthalmol. 2020;138(5):575–578.
  6. Baig AM. Neurological manifestations in COVID-19 caused by
    SARS-CoV-2. CNS Neurosci Ther. 2020;26(5):499-501.
  7. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for
    mortality of adult inpatients with COVID-19 in Wuhan, China:
    a retrospective cohort study. Lancet 2020;395:1054-1062.
  8. Magro C, Mulvey JJ, Berlin D, et al. Complement associated
    microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases [published online ahead of print, April 15, 2020]. Transl Res. 2020;S1931-5244
    (20)30070-0.
    Authors
    Vijairam Selvaraj, MD, Division of Hospital Medicine, The Miriam
    Hospital, Providence, RI; Department of Infectious Diseases,
    Warren Alpert Medical School of Brown University.
    Daniel Sacchetti, DO, Warren Alpert Medical School of Brown
    University; Brown Neurology, Providence, RI.
    Arkadiy Finn, MD, Division of Hospital Medicine, The Miriam
    Hospital, Providence, RI; Department of Infectious Diseases,
    Warren Alpert Medical School of Brown University.
    Kwame Dapaah-Afriyie, MD, Division of Hospital Medicine, The
    Miriam Hospital, Providence, RI; Department of Infectious
    Diseases, Warren Alpert Medical School of Brown University

4 Ways COVID Leaves Its Mark on the Eye

Authors: Reena Mukamal American College of Opthalmology

An analysis of 121 patients dating back to the beginning of the pandemic unveils COVID’s most common effects on the eye. Share this information and remember: Widespread vaccination is key to ending the pandemic.

How does COVID reach the eyes?

People respond in different ways to COVID-19 infections. While some people develop mild to severe respiratory problems, others experience no symptoms at all. Pink eye remains the most common sign of COVID in the eyes of children and adults.

Doctors are still learning how COVID affects the eyes. But it’s clear that some people with COVID experience inflammation throughout their body. This inflammation can cause blood clots to form. These clots may travel through the body and reach the veins, arteries and blood vessels of the eye.

COVID’s effects on the retina

The new study suggests that few people with COVID will develop eye problems. But when those problems occur, they can range from mild to vision-threatening. Many of these problems affect the retina — a light-sensing layer of cells in the back of the eye that plays a key role in your vision.

Here are four of the most common eye problems that may develop after COVID infection, according to the new analysis.

1. “Cotton wool” spots

When blood clots prevent nutrients from getting to the retina, the tissue in the retina begins to swell and die. If the doctor examines your eye closely using optical coherence tomography, this area looks white and fluffy like cotton wool (shown in the image above). These spots do not typically affect a person’s vision.

2. Eye stroke (also called retinal artery occlusion)

Blood clots in the arteries of the retina can block the flow of oxygen, causing cells to die. This is known as a retinal artery occlusion, or eye stroke. The most common symptom of an eye stroke is sudden, painless vision loss.

3. Retinal vein occlusion

When a vein in the retina becomes blocked, blood can’t drain out like it should. The buildup of blood raises pressure levels inside the eye, which can cause bleeding, swelling and fluid leaks. People with this complication can develop blurry vision or even sudden, permanent blindness.

4. Retinal hemorrhage

This occurs when blood vessels in the retina start bleeding. It is sometimes caused by a retinal vein occlusion. A hemorrhage can lead to blind spots and gradual or sudden loss of vision.

Am I at risk of eye complications from COVID?

Very few people with COVID will experience serious eye-related complications. But certain people are more likely than others to develop these problems. People with the following conditions are at greatest risk:

When eye problems occur, they tend to develop within 1 to 6 weeks of experiencing COVID symptoms.

These problems have developed in people who were very sick with COVID as well as people who were apparently healthy and lacked symptoms.

Although this is the largest study to date on COVID’s impact on the retina, researchers only examined information from 121 patients. Doctors are continuing to explore how often eye problems affect people with COVID, and how to prevent these conditions.

How to protect your eyes during COVID-19

If you develop symptoms of COVID and notice changes in your vision, schedule an appointment with an ophthalmologist right away.

To protect your eyes and your overall health, be sure to wear a face mask around other people, wash and sanitize your hands frequently and get vaccinated against COVID-19. The potential complications of the disease far outweigh any complications from the vaccine.

Covid Linked To Disorder That Causes Sudden Vision Loss, Study Says

Authors: Zachary Snowdon Smith FORBES 2022

TOPLINE

Covid-19 infection is linked to eye conditions called retinal vascular occlusions—blockages of blood vessels in the eye that can cause vision loss—according to a study published Thursday by JAMA Ophthalmology that threw light on one of several little-understood long-term effects of the virus.

KEY FACTS

The first condition, called retinal artery occlusions, can cause sudden blurring or loss of vision in one eye, and was found to have increased 29.9% in the period two to 26 weeks after Covid-19 diagnosis compared to the period 26 to two weeks before diagnosis, researchers concluded.

The second condition, retinal vein occlusions, causes similar symptoms to retinal artery occlusions and was even more strongly associated with Covid-19, with a 47% increase in the period two to 26 weeks after Covid-19 diagnosis compared to the period 26 to two weeks before diagnosis, according to the study.

The strong association between Covid-19 and retinal vein occlusions seems to confirm previous research suggesting that Covid-19 generally affects veins more severely than arteries, researchers said—a finding that could help guide treatment approaches for Covid-19 patients.

Even following Covid-19 infection, retinal vascular occlusions remained rare, with retinal artery occlusions affecting about 1 in 333,333 patients and retinal vein occlusions affecting about 1 in 81,967 patients during the period two to 26 weeks after they were diagnosed.

Researchers did not find that Covid-19 patients who were hospitalized were more likely to experience retinal vascular occlusions than those who were not hospitalized.

The study included 432,515 patients without a history of retinal vascular occlusions more than six months prior to their Covid-19 diagnosis, and who were diagnosed with the virus between January 20, 2020 and May 31, 2021.

TANGENT

Retinal vascular occlusions are caused when blood clots or fat deposits block blood vessels in the retina, the part of the eye that receives light and transmits images to the brain. These occlusions may cause damage ranging from slight vision impairments to whole-eye vision loss. Retinal artery occlusion is linked to diabetes, high blood pressure, elevated levels of fat in blood and various disorders affecting the heart or the carotid artery, according to the National Library of Medicine’s MedlinePlus service. Retinal vein occlusion is linked to diabetes, high blood pressure, fatty buildup in the arteries and eye disorders like glaucoma. Outcomes are variable: while many patients regain a degree of vision, there are no reliable treatments for whole-eye vision loss due to a retinal vascular occlusion. These occlusions may indicate the presence of clots or fat deposits elsewhere in the body, warning of a risk of stroke, according to Johns Hopkins Medicine.

KEY BACKGROUND

Though Covid-19’s immediate symptoms have been well documented, scientists have struggled to understand the longer-term effects of the virus. A study published Monday by JAMA Neurology determined that the long-term smell loss reported by some Covid-19 patients is tied to damage to the olfactory bulb, the part of the brain that processes smells. Covid-19 has also been associated with a range of vascular issues such as inflammation of the heart muscle or the sac containing the heart. Some researchers have concluded that much of the damage caused by the coronavirus is not directly inflicted by the virus itself, but by infection symptoms like inflammation, the New York Times reports. The authors of the JAMA Ophthalmology study suggested a similar interpretation, theorizing that the initial vascular damage caused by Covid-19 infection might make some people more vulnerable to a pre-existing risk of retinal vascular occlusions.

CONTRA

It’s possible that the JAMA Ophthalmology study underestimated the risk of retinal vascular occlusions among severely ill patients because those patients’ conditions may have prevented them from informing healthcare staff of vision changes, researchers said.

WHAT WE DON’T KNOW

Further research would be necessary to establish a cause-and-effect relationship between Covid-19 infection and retinal vascular occlusions, researchers said. The JAMA Ophthalmology study established only an association between the two conditions.

Eye and SARS-CoV-2 in 2022

Authors: Andrzej Grzybowski, M.D., Ph.D, Department of Ophthalmology, University of Warmia and Mazury in Olsztyn Institute of Ophthalmology Research, Ophthalmology Foundation 21 in Poznan

Abstract
The ocular symptoms of COviD-19 are rare, however, the most common is conjunctivitis. Retinal changes, including dilated veins, tortuous blood vessels, intraretinal hemorrhages, and cotton balls are much less common. in addition, there may be swelling of the eyelids, their irritation, most often in combination with conjunctival hyperemia. Moreover, COviD-19 infection may be accompanied by different neuro-ophthalmic disorders and, in rare cases, by mucormycosis. various ocular complications have been reported following vaccination against COviD-19, including facial nerve palsy, abduction nerve palsy, acute macular neuro-retinopathy, superior ocular vein thrombosis, corneal transplant rejection, membrane inflammation vascular eye disease, central serous chorioretinopathy, reactivation of vogt-Koyanagi-Harada disease and onset of Graves’ disease. Chemical eye injuries in children caused by hand sanitizers have also been reported. Although numerous studies have confirmed the antiviral activity of benzalkonium chloride, its role in this regard requires further research.

Introduction
COviD-19 pandemic continues to pose serious health and economic challenge worldwide. After 2 years, attempts can be made to summarize the accumulated knowledge on the transmission and ocular symptoms of SARS-Cov-2 infection, post-vaccination ocular manifestations, antiseptics-related ocular damage in children and antiviral activity of some substances commonly found in eye drops, such as benzalkonium chloride (BAK). The following article is a discussion of the literature review on the above issues in the years 2020–2021.ocular penetration of the virus. The angiotensin converting enzyme 2 (ACE2) receptor, the major SARS-Cov-2 binding protein, is present in relatively
high concentrations in the conjunctiva, cornea, and retina, allowing viral tropism to the eye and potentially transmission to ocular structures [1, 2]. Although the main route of SARS-Cov-2 transmission is through the respiratory tract transmission of the virus to the eye may also occur in rare cases. initial reports from Wuhan, China in 2019 described the spread of SARS-Cov-2 among physicians wearing N95masks but without eye protection [3]. The proposed mechanism of transmission to the eye involves binding of the virus to ACE2 receptors on the surface of the conjunctiva, followed by transmission to the airways via the nasolacrimal duct [4]. However, the likelihood of SARS-Cov-2 transmission to the eye is generally considered low. The published conjunctival smear rates in patients with SARS-Cov-2 have ranged from 0% to 16.7% and are probably even lower in patients without ocular symptoms, suggesting limited viral titers in the eye. Patients with confirmed SARS-Cov-2 infection usually did not show excretion of virus particles in tear secretions [5]. Certain conjunctival enzymes, includingADAR-1 and APOBEC3A, are thought to provide natural antiviral protection, reducing virus titers in the conjunctiva and minimizing the risk of their further transmission [6]. itis currently recommended that goggles or face shields workers with a high potential risk of transmission to the eye, as well as slit lamp shields [5, 7–9]. Ophthalmologists may be particularly exposed to SARSCov-2 particles during aerosolization procedures, including tonometry testing, as well as slit lamp examination.


Table 1
The most common ocular manifestations associated with SARS-CoV-2 infection.
• Conjunctivitis and conjunctival congestion
• Eyelid lesions
• Retinal and choroidal pathologies
• Inflammatory pathologies (keratitis, epididymitis, uveitis)
• Neuro-ophthalmic pathologies
• Naso-orbital mucormycosis
ocular lesions in the course of coVID-19 (tab. 1) The most common ocular manifestation of COviD-19 is conjunctivitis, particularly conjunctival congestion and discharge from the conjunctival sac [2, 10, 11]. These occur in 8–7.7% of COviD-19 patients [2, 12, 13] and up to 32% of hospitalized patients [14]. Conjunctivitis usually begins 1–2 weeks after the onset of symptoms [14]. interestingly, it may be the only symptom present in otherwise asymptomatic children [15, 16]. Although conjunctivitis itself is largely benign and self-limiting, it can occur in up to 55% of children withCOviD-19-related polyarthritis, a more serious condition requiring urgent attention. Therefore, children with conjunctival symptoms should be investigated for other associated symptoms, including rash, lymphadenopathy, and limb edema [17]. Swelling of the eyelids was found in 0.9% of COviD-19 patients, their irritation in 4.9% of individuals, most often in combination with conjunctival congestion [11, 18–20]. Retinal lesions were mainly observed in hospitalized COviD-19 patients with moderate to severe disease [5]. The patho-mechanism of retinal damage is still not understood, but it may result from direct cytotoxic effects of the virus or, in the case of microangiopathy and vasculitis, from endothelial cell damage [1, 5]. One cross-sectional study of asymptomatic COviD-19 patients showed dilated venous vessels (27.7%), tortuous blood vessels (12.9%), intraretinal hemorrhages (9.3%), and cotton wool spots (7.4%) [21]. Edema of the optic nerve disc and whitish retinal staining have also been described in isolated cases [22–25]. Systemic inflammation and propensity for venous and arterial thromboembolic complications in COviD-19 predisposes patients to the development of arterial or venous retinal obstruction, as described in several patients with severe COviD-19 [22, 26 28].inflammatory conditions of the eye, including cornea, epithelium, or uvea, are rarely described as occurring in COviD-19 patients [11, 29–31]. The absence of SARS–Cov-2 in the conjunctiva in most cases of this type of inflammation suggests that a cytokine-induced inflammatory response (rather than direct viral action) may play a major role in the pathogenesis. Furthermore, it is worth remembering. that dysregulated and systemic immune responses in patients with COviD-19 may also predispose to the development of inflammatory ocular pathologies such as uveitis. Neuro-ophthalmic manifestations in COviD-19 patients are usually rare and may result from direct viral neuroinvasion, virus-induced immune responses and cytokine storms, and delayed post-infectious immune activation [32]. These include optic nerve disc edema, optic neuritis in young patients after COviD-19 has resolved (may reflect a para-infectious demyelinating syndrome) [33], cranial nerve neuropathies (most commonly, paralysis of the inferior alveolar nerve) [34–37], double vision (possibly due to inflammatory demyelinating neuropathy) [34]. Most patients did not require specific treatment, and symptoms resolved spontaneously within 1–2 weeks in the vast majority of cases. Double vision, ophthalmoplegia and eyelid drooping have also been described in the course of Guillain-Barré and Miller-Fisher syndromes, probably caused by post-viral inflammation with COviD-19 [38–41]. Many of these patients experienced at least partial resolution of symptoms after intravenous immunoglobulin treatment. Mucormycosis is a life-threatening infection caused by filamentous molds that most commonly causes localized nasal or nasal-orbital symptoms or, less commonly, disseminated infection. These infections are classically associated with immunocompromised and diabetic patients. Patients with severe COviD-19 often have comorbidities that may predispose them to mucormycosis, and the use of systemic corticosteroids as standard therapy likely further contributes to its development [42–45]. ocular adverse Events Following coVID-19 vaccination There are a growing number of reports in the literature on ocular adverse events following COviD-19 vaccination. One major review of this issue discussed 23 articles reporting ocular lesions associated with Covid- v9vaccination [46]. Ocular complications were reported in 74 patients-including facial nerve palsy, paralysis of the abducens nerve, acute adrenomyeloneuropathy (AMN,), superior ocular vein thrombosis, corneal graft rejection, uveitis, central serous chorioretinopathy, reactivation of Vogt-Koyanagi-Harada syndrome (vKH) and onset of Graves-Basedow disease [46]. Complications occurred in 7 cases after AZD1222 vaccine, Oxford/ Astra-Zeneca, 15 cases after BNT162b2 vaccine, Pfizer-BioNTech, and 1 case after BBiBP-Corv vaccine, Sinopharm [46]. The published descriptions primarily include retrospective case groups or single case reports and inherently provide insufficient information to establish association or causality. Nevertheless, the described presentations resemble the reported ocular manifestations of COviD-19. Therefore, it appears that the human immune response to COviD-19 vaccination may be involved in the pathogenesis of ocular side effects after COviD-19 vaccination. A recently published original article involving a retrospective analysis of cases from a region in italy identified 34 patients with uveitis and other ocular complications after COviD-19 vaccination [47]. Three cases of herpetic keratitis, two anterior scleritis, five (AU), three retinitis due to toxoplasma, two reactivations of vKH syndrome, two pars plaints, two retinal vasculitis, one bilateral uveitis and onset of Behçet’s disease, three multiple evanescent white dot syndromes (MEWDS), one acute AMN, five retinal vein occlusions (RvO), one non-arteritis anterior ischemic optic neuropathy (Nation) three activations of inactive choroidal neovascularization (CNv) secondary to myopia or uveitis and one central serous chorioretinopathy (CSCR). The mean time between vaccination and onset of ocular complications was 9.4 days (range 1–30 days). 23 cases occurred after Pfizer-BioNTech vaccination (mRNA BNT162b2), 7 after Oxford/ AstraZeneca vaccination (ChAdOx1 nCov-19), after Moderna vaccination (mRNA-1273) and 1 after Janssen Johnson & Johnson vaccination (Ad26.COv2) [47]. it should be noted, that the number of reported cases of ocular adverse events after vaccination is extremely small – at the end of 2021, approximately 60% of the world population was vaccinated and approximately 10 billion vaccinations were performed [48]. Unintentional ocular consequences oF hands Disinfectant Use Numerous eye injuries in children due to inadvertent contact with alcohol-based hand sanitizers have been described [49, 50]. Martin et al. found a sevenfold increase in eye exposure in children in 2020, with a corresponding increase in the number of corrective surgeries [49]. children exposure is most likely due to the placement of the sanitizer dispenser near their face. Dispensers, often pressure-controlled with a pedal, allow for unit doses of disinfectants. However, they typically placed about 1 m high, i.e., at the eye level of young children. in addition, the delay in eye washing due to the lack of access to water or the viscosity of some formulations is very harmful to the ocular surface [49]. Therefore, efforts should be made to isolate automatic disinfectant dispensers from children. Where possible, it is important to redesign dispensers. Signage warning of the potential danger of eye contact mus be placed. in addition, education regarding conduct in theevent of an injury needs to be introduced – in an emergency, any clear liquid can be used to rinse the eye after exposure to chemicals. Furthermore, parents need to know the importance of examining their child’s eyes after a chemical injury, as early diagnosis and treatment will reduce the long-term consequences of eye damage. Efficacy oF benzalkonium chloride against coronaviruses Benzalkonium chloride is a substance classified as a quaternary ammonium compound (QAC). it is a surfactant whose activity changes the structure of the lipid layer – it is absorbed by negatively charged phosphate heads of phospholipids in the lipid layer. An increase in the concentration of BAK causes a decrease in the fluidity of the bacterial cell membrane, hydrophilic gaps are formed in it, which consequently leads to increased permeability and its damage [51]. Features of BAK that give it an advantage over alcohol-containing disinfectants include lower toxicity, less skin irritation, and non-flammable nature. According to the US Center for Disease Control and Prevention (CDC) [52], there is currently no better alternative for skin disinfection than agents containing ethanol over 60% or isopropanol 70%. Benzalkonium chloride, along with ethanol and isopropanol, is approved by the US Food and Drug Administration (FDA) for use in hand disinfectant formulations for medical personnel. However, the CDC reports that available scientific evidence indicates that BAK is less effective against certain bacteria and viruses compared to the above-mentioned alcohols. The authors reviewed recent scientific literature to evaluate the antiviral efficacy of BAK. Schrank et al. presented microbiological data obtained with BAK at different concentrations and highlighted its variable efficacy in reducing viral activity [53]. Furthermore, the researchers summarized the available data on the efficacy of BAK in inactivating different strains belonging to coronaviruses. Among others, they reported that in a study by Pratelli et al. that analyzed the effect of disinfectants on coronavirus present in dogs, the authors noted that BAK did not reduce viral load, although it induced significant morphological damage to the iris [53]. in addition, Ansaldi et al. demonstrated that BAK 1% reduced SARS-Cov-2 virus replication after 5 min of treatment; however, viral RNA was detectable by RT-PCR even after 30 min of exposure [53]. A study by Meister et al. on the antiviral efficacy of oral rinses against SARS-Cov-2 showed that a product containing BAK 0.035% significantly reduced virus infectivity up to undetectable levels [54]. Another study on three surface disinfectants (two of which contained BAK 0.5%) demonstrated the efficacy of BAK. Exposure times were 30 min and 60 min in three parallel experiments conducted on three organic materials: albumin 0.3%, fetal calf serum 10%, and albumin 0.3% with sheep erythrocytes. Agents containing BAK 0.5% showed a more than fourfold reduction of SARS-Cov-2 virus, resulting in inactivation below its detection level [55]. Kampf et al. collected available data on the effects of different disinfectants on the inactivation efficiency and persistence of viruses (SARS, MERS, HCoV) on different surfaces [56]. BAK at concentrations of 0.05–0.2% was found to be less effective than other antiviral agents tested [56]. Ogilvie et al. analyzed the efficacy of alcohol-free disinfectants and highlighted that a hand sanitizer containing effectively inactivates SARS-Cov-2 [57]. On this basis, it was approved by the FDA for hand disinfection in COviD-19 prevention. Pedreira et al. summarized the effectiveness of disinfection and control of SARS-Cov-2 in the food industry [58]. According to the authors, BAK is
effective in controlling and inactivating coronaviruses, although it requires much longer exposure to achieve the desired effect [58]. Hirose et al. analyzed the efficacy of various disinfectants including ethanol, isopropanol, BAK, and chlorhexidine in inactivating SARS-Cov-2 and influenza A virus. Studies have been performed in vitro and on a skin model collected during autopsy procedures [59]. Antiviral efficacy of benzalkonium chloride in vitro [59]:
• BAK was significantly less effective compared with ethanol at concentrations of 80%, 60% and 40% and isopropanol at concentration of 70%, whose logarithm of viral load reduction was above 4 in each case.
• BAK at a concentration of 0.05% was least effective atoll three application times, i.e., after 5 s, 15 s, and 60 s, and the logarithm of viral load reduction was 1.33,1.75, and 2.17, respectively.
• BAK at a concentration of 0.2% was ineffective at short application times, i.e., after 5 s and 15 s, during which the logarithm of viral load reduction was 1.83 and 2.42, respectively. Application of BAK for 60 s increased the eradication efficiency of SARS-CoV-2 virus (logarithm of reduction was 3.00).
Antiviral efficacy of benzalkonium chloride in a sigmodal study [59]:
• The study showed that BAK has higher efficacy in inactivating novel coronavirus on skin model than in vitro.
• The efficacy of BAK at a concentration of 0.05% was low at all three application times, i.e., after 5 s, 15 and 60 s, and the logarithm of viral load reduction was 2.03, 2.19 and 2.36, respectively.
• Increasing the concentration of BAK to 0.2% resulted in an increase in disinfection efficiency at all three application times. The logarithm of reduction for 5-, 15-,and 60-second applications was 2.72, 2.92, and 3.19,respective

• As in vitro, ethanol at concentrations of 80%, 60% and40% and isopropanol 70% proved to be most effective in eradicating the virus on the skin model (logarithm of reduction above 4). in conclusion, the literature review conducted on the efficacy of BAK against coronaviruses is ambiguous and inconclusive. Some studies have confirmed that BAK is effective deactivating the virus; however, it is significantly less effective than alcohol formulations. The efficacy of BAK increases with concentration and with time of application; however, this may be influenced by its toxicity or adverse
effects. conclusions
• Although ocular manifestations in COVID-19 patients are relatively rare, conjunctivitis and retinal changes in more severe cases are among the most common (tab. 1).
• The ophthalmologist is potentially exposed to SARS–CoV-2 virus infection, so personal protection in the form of goggles and a slit lamp shield is recommended.
• COVID-19 vaccination may be accompanied by ocular adverse events.
• In recent years, an increasing number of cases o hand-sanitizer chemical trauma to children’s eyes
have been observed, necessitating appropriate preventive measures.
• Although numerous studies have demonstrated the antiviral activity of BAK, its role in this regard needs further investigation.

References

  1. Jevnikar K, Jaki Mekjavic P, Vidovic Valentincic N et al. An Update on COVID-19 Related Ophthalmic Manifestations. Ocul Immunol Inflamm. 2021; 29(4): 684-9. http://doi.org/10.1080/09273948.2021.1896008.
  2. Zhong Y, Wang K, Zhu Y et al. Ocular manifestations in COVID-19 patients: A systematic review and meta-analysis. Travel Med Infect Dis.
    2021; 44: 102191. http://doi.org/10.1016/j.tmaid.2021.102191.
  3. Deng W, Bao L, Gao H et al. Ocular conjunctival inoculation of SARS-CoV-2 can cause mild COVID-19 in rhesus macaques. Nat Commun.
    2020; 11(1): 4400. http://doi.org/10.1038/s41467-020-18149-6.
  4. Seah IYJ, Anderson DE, Kang AEZ et al. Assessing Viral Shedding and Infectivity of Tears in Coronavirus Disease 2019 (COVID-19) Patients. Ophthalmology. 2020; 127(7): 977-9. http://doi.org/10.1016/j.ophtha.2020.03.026.
  5. Szczęśniak M, Brydak-Godowska J. SARS-CoV-2 and the Eyes: A Review of the Literature on Transmission, Detection, and Ocular Manifestations. Med Sci Monit. 2021; 27: e931863. http://doi.org/10.12659/msm.931863.
  6. Leonardi A, Rosani U, Brun P. Ocular Surface Expression of SARS-CoV-2 Receptors. Ocul Immunol Inflamm. 2020; 28(5): 735-8. http://doi.
    org/10.1080/09273948.2020.1772314.
  7. Chen YY, Yen YF, Huang LY et al. Manifestations and Virus Detection in the Ocular Surface of Adult COVID-19 Patients: A Meta-Analysis.
    J Ophthalmol. 2021; 2021: 9997631. http://doi.org/10.1155/2021/9997631.
  8. Almazroa A, Alamri S, Alabdulkader B et al. Ocular transmission and manifestation for coronavirus disease: a systematic review. Int
    Health. 2021. http://doi.org/10.1093/inthealth/ihab028.
  9. American Academy of Ophthalmology. Important coronavirus updates for ophthalmologists. https://www.aao.org/headline/alert-important-coronavirus-context (access: 17.01.2022).
  10. Jin YP, Trope GE, El-Defrawy S et al. Ophthalmology-focused publications and findings on COVID-19: A systematic review. Eur J Ophthalmol. 2021; 31(4): 1677-87. http://doi.org/10.1177/1120672121992949.
  11. Nasiri N, Sharifi H, Bazrafshan A et al. Ocular Manifestations of COVID-19: A Systematic Review and Meta-analysis. J Ophthalmic Vis Res.
  12. 2021; 16(1): 103-12. http://doi.org/10.18502/jovr.v16i1.8256.
  13. Ulhaq ZS, Soraya GV. The prevalence of ophthalmic manifestations in COVID-19 and the diagnostic value of ocular tissue/fluid. Graefes
  14. Arch Clin Exp Ophthalmol. 2020; 258(6): 1351-2. http://doi.org/10.1007/s00417-020-04695-8.
  15. Aggarwal K, Agarwal A, Jaiswal N et al. Ocular surface manifestations of coronavirus disease 2019 (COVID-19): A systematic review and
  16. meta-analysis. PLoS One. 2020; 15(11): e0241661. http://doi.org/10.1371/journal.pone.0241661.
  17. Wu P, Duan F, Luo C et al. Characteristics of Ocular Findings of Patients With Coronavirus Disease 2019 (COVID-19) in Hubei Province,
  18. China. JAMA Ophthalmol. 2020; 138(5): 575-8. http://doi.org/10.1001/jamaophthalmol.2020.1291.
  19. Ma N, Li P, Wang X et al. Ocular Manifestations and Clinical Characteristics of Children With Laboratory-Confirmed COVID-19 in Wuhan,
  20. China. JAMA Ophthalmol. 2020; 138(10): 1079-86. http://doi.org/10.1001/jamaophthalmol.2020.3690.
  21. Wu P, Liang L, Chen C et al. A child confirmed COVID-19 with only symptoms of conjunctivitis and eyelid dermatitis. Graefes Arch Clin
  22. Exp Ophthalmol. 2020; 258(7): 1565-6. http://doi.org/10.1007/s00417-020-04708-6.
  23. Wang JG, Zhong ZJ, Li M et al. Coronavirus Disease 2019-Related Multisystem Inflammatory Syndrome in Children: A Systematic Review
  24. and Meta-Analysis. Biochem Res Int. 2021; 2021: 5596727. http://doi.org/10.1155/2021/5596727.
  25. Daruich A, Martin D, Bremond-Gignac D. Ocular manifestation as first sign of Coronavirus Disease 2019 (COVID-19): Interest of telemedicine during the pandemic context. J Fr Ophtalmol. 2020; 43(5): 389-91. http://doi.org/10.1016/j.jfo.2020.04.002.
  26. Azari AA, Barney NP. Conjunctivitis: a systematic review of diagnosis and treatment. JAMA. 2013; 310(16): 1721-9. http://doi.org/10.1001/
  27. jama.2013.280318.
  28. Sindhuja K, Lomi N, Asif MI et al. Clinical profile and prevalence of conjunctivitis in mild COVID-19 patients in a tertiary care COVID-19
  29. hospital: A retrospective cross-sectional study. Indian J Ophthalmol. 2020; 68(8): 1546-50. http://doi.org/10.4103/ijo.IJO_1319_20.
  30. Invernizzi A, Torre A, Parrulli S et al. Retinal findings in patients with COVID-19: Results from the SERPICO-19 study. EClinicalMedicine.
  31. 2020; 27: 100550. http://doi.org/10.1016/j.eclinm.2020.100550.
  32. Insausti-García A, Reche-Sainz JA, Ruiz-Arranz C et al. Papillophlebitis in a COVID-19 patient: inflammation and hypercoagulable state.
  33. Eur J Ophthalmol. 2020: 1120672120947591. http://doi.org/10.1016/j.jstrokecerebrovasdis.2020.104982.
  34. Gascon P, Briantais A, Bertrand E et al. Covid-19-associated retinopathy: a case report. Ocul Immunol Inflamm. 2020; 28(8): 1293-7.
  35. Benito-Pascual B, Gegúndez JA, Díaz-Valle D et al. Panuveitis and optic neuritis as a possible initial presentation of the novel coronavirus
  36. disease 2019 (COVID-19). Ocul Immunol Inflammation. 2020; 28(6): 922-5.
  37. Acharya S, Diamond M, Anwar S et al. Unique case of central retinal artery occlusion secondary to COVID-19 disease. IDCases. 2020; 21:
  38. e00867.
  39. Dumitrascu OM, Volod O, Bose S et al. Acute ophthalmic artery occlusion in a COVID-19 patient on apixaban. J Stroke Cerebrovasc Dis.
  40. 2020; 29(8): 104982. http://doi.org/10.1016/j.jstrokecerebrovasdis.2020.104982.
  41. Sheth JU, Narayanan R, Goyal J et al. Retinal vein occlusion in COVID-19: A novel entity. Indian J Ophthalmol. 2020; 68(10): 2291-3. http://
  42. doi.org/10.4103/ijo.IJO_2380_20.
  43. Bostanci Ceran B, Ozates S. Ocular manifestations of coronavirus disease 2019. Graefes Arch Clin Exp Ophthalmol. 2020; 258(9): 1959-63.
  44. http://doi.org/10.1007/s00417-020-04777-7.
  45. Méndez Mangana C, Barraquer Kargacin A, Barraquer RI. Episcleritis as an ocular manifestation in a patient with COVID-19. Acta Ophthalmol. 2020; 98(8): e1056-e7. http://doi.org/10.1111/aos.14484.
  46. Otaif W, Al Somali AI, Al Habash A. Episcleritis as a possible presenting sign of the novel coronavirus disease: A case report. Am J Ophthalmol Case Rep. 2020; 20: 100917. http://doi.org/10.1016/j.ajoc.2020.100917.
  47. Iriqat S, Yousef Q, Ereqat S. Clinical Profile of COVID-19 Patients Presenting with Uveitis – A Short Case Series. Int Med Case Rep J. 2021;
  48. 14: 421-7. http://doi.org/10.2147/imcrj.S312461.
  49. Ortiz-Seller A, Martínez Costa L, Hernández-Pons A et al. Ophthalmic and Neuro-ophthalmic Manifestations of Coronavirus Disease
  50. 2019 (COVID-19). Ocul Immunol Inflamm. 2020; 28(8): 1285-9.
  51. Zhou S, Jones-Lopez EC, Soneji DJ et al. Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis and Myelitis in
  52. COVID-19. J Neuroophthalmol. 2020; 40(3): 398-402. http://doi.org/10.1097/wno.0000000000001049.
  53. Manolopoulos A, Katsoulas G, Kintos V et al. Isolated Abducens Nerve Palsy in a Patient With COVID-19: A Case Report and Literature
  54. Review. Neurologist. 2021. http://doi.org/10.1097/nrl.0000000000000382.
  55. Francis JE. Abducens Palsy and Anosmia Associated with COVID-19: A Case Report. Br Ir Orthopt J. 2021; 17(1): 8-12. http://doi.
  56. org/10.22599/bioj.167.
  57. Dinkin M, Gao V, Kahan J et al. COVID-19 presenting with ophthalmoparesis from cranial nerve palsy. Neurology. 2020; 95(5): 221-3.
  58. http://doi.org/10.1212/wnl.0000000000009700.
  59. Greer CE, Bhatt JM, Oliveira CA et al. Isolated Cranial Nerve 6 Palsy in 6 Patients With COVID-19 Infection. J Neuroophthalmol. 2020;
  60. 40(4): 520-2.
  61. Zhao H, Shen D, Zhou H et al. Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence? Lancet Neurol.
  62. 2020; (5): 383-4. http://doi.org/10.1016/s1474-4422(20)30109-5.
  63. Caress JB, Castoro RJ, Simmons Z et al. COVID-19-associated Guillain-Barré syndrome: The early pandemic experience. Muscle Nerve.
  64. 2020; 62(4): 485-91. http://doi.org/10.1002/mus.27024.
  65. Gutiérrez-Ortiz C, Méndez-Guerrero A, Rodrigo-Rey S et al. Miller Fisher syndrome and polyneuritis cranialis in COVID-19. Neurology.
  66. 2020; 95(5): e601-e5. http://doi.org/10.1212/wnl.0000000000009619.
  67. Reyes-Bueno JA, García-Trujillo L, Urbaneja P et al. Miller-Fisher syndrome after SARS-CoV-2 infection. Eur J Neurol. 2020; 27(9): 1759-61.
  68. http://doi.org/10.1111/ene.14383.
  69. Sundaram N, Bhende T, Yashwant R et al. Mucormycosis in COVID-19 patients. Indian J Ophthalmol. 2021; 69(12): 3728-33.
  70. Fathima AS, Mounika VL, Kumar VU et al. Mucormycosis: A triple burden in patients with diabetes during COVID-19 Pandemic. Health
  71. Sci Rev (Oxf). 2021; 1: 100005. http://doi.org/10.1016/j.hsr.2021.100005.
  72. Bhattacharyya A, Sarma P, Kaur H et al. COVID-19-associated rhino-orbital-cerebral mucormycosis: A systematic review, meta-analysis,
  73. and meta-regression analysis. Systematic Review and Meta-Analysis. Indian J Pharmacol. 2021; 53(6): 499-510. http://doi.org/10.4103/
  74. ijp.ijp_839_21.
  75. Sen M, Honavar SG, Sharma N et al. COVID-19 and Eye: A Review of Ophthalmic Manifestations of COVID-19. Indian J Ophthalmol. 2021;
  76. 69(3): 488-509. http://doi.org/10.4103/ijo.IJO_297_21.
  77. Ng XL, Betzler BK, Testi I et al. Ocular Adverse Events After COVID-19 Vaccination. Ocul Immunol Inflamm. 2021; 24: 1-9. http://doi.org/
  78. 10.1080/09273948.2021.1976221.
  79. Bolletta E, Iannetta D, Mastrofilippo V et al. Uveitis and Other Ocular Complications Following COVID-19 Vaccination. J Clin Med. 2021;
  80. 10(24): 5960.
  81. https://ourworldindata.org/covid-vaccinations.
  82. Martin GC, Le Roux G, Guindolet D et al. Pediatric Eye Injuries by Hydroalcoholic Gel in the Context of the Coronavirus Disease 2019
  83. Pandemic. JAMA Ophthalmol. 2021; 139(3): 348-51.
  84. Yangzes S, Grewal S, Gailson T et al. Hand Sanitizer–Induced Ocular Injury: A COVID-19 Hazard in Children. JAMA Ophthalmol. 2021;
  85. 139(3): 362-4. http://doi.org/10.1001/jamaophthalmol.2020.6351.
  86. Merchel Piovesan Pereira B, Tagkopoulos I. Benzalkonium Chlorides: Uses, Regulatory Status, and Microbial Resistance. Appl Environ
  87. Microbiol. 2019; 85(13): e00377-19.
  88. https://www.cdc.gov/coronavirus/2019-ncov/hcp/hand-hygiene.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fhcp%2Fhand-hygiene-faq.html (access: 12.09.2021).
  89. Schrank CL, Minbiole KPC, Wuest WM. Are Quaternary Ammonium Compounds, the Workhorse Disinfectants, Effective against Severe
  90. Acute Respiratory Syndrome-Coronavirus-2? ACS Infect Dis. 2020; 6(7): 1553-7.
  91. Meister TL, Brüggemann Y, Todt D et al. Virucidal Efficacy of Different Oral Rinses Against Severe Acute Respiratory Syndrome Coronavirus 2. J Infect Dis. 2020; 222(8): 1289-92.
  92. Rabenau HF, Kampf G, Cinatl J et al. Efficacy of various disinfectants against SARS coronavirus. J Hosp Infect. 2005; 61(2): 107-11.
  93. Kampf G, Todt D, Pfaender S et al. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents. J Hosp
  94. Infect. 2020; 104(3): 246-51.
  95. Ogilvie BH, Solis-Leal A, Lopez JB et al. Alcohol-free hand sanitizer and other quaternary ammonium disinfectants quickly and effectively inactivate SARS-CoV-2. J Hosp Infect. 2021; 108: 142-5.
  96. Pedreira A, Taşkın Y, García MR. A Critical Review of Disinfection Processes to Control SARS-CoV-2 Transmission in the Food Industry.
  97. Foods. 2021; 10(2): 283.
  98. Hirose R, Bandou R, Ikegaya H et al. Disinfectant effectiveness against SARS-CoV-2 and influenza viruses present on human skin: model-based evaluation. Clin Microbiol Infect. 2021; 27(7): 1042.e1-1042.e

.