HomeOphthalmologyOphthalmology NewsCOVID-19 Vaccinations, and subsequent abnormalities in the retina

COVID-19 Vaccinations, and subsequent abnormalities in the retina

Pichi and colleagues1 in this issue of JAMA Ophthalmology describe ocular adverse events after Sinopharm COVID-19 vaccination, together with 4 retinal events. Only some information is known about this vaccine.2

Regardless of the big variety of doses of vaccine having been administered worldwide, its adverse systemic events stay unsure. We’ll overview the evidence regarding associations of COVID-19 infection or COVID-19 vaccination with subsequent ocular adverse events, in particular retinal problems, to contemplate whether these abnormalities are causally related or simply coincidental.



COVID-19 infection causes widespread damage to multiple organs. Proinflammatory cytokines are released and are strong inducers of a procoagulant/prothrombotic reaction,3 leading to intravascular coagulopathies and endothelial injury. In regard to the retina, COVID-19 an infection will be associated with anemia, hypertension or hypotension, hypoxia, and different systemic morbidities, which might contribute to retinal findings resembling nerve fiber layer infarcts, hemorrhages, or microaneurysms.

Vasculitis and thromboembolism can also contribute to retinal ischemia. Thus, we’re not surprised to see reports of retinal hemorrhages, dilated and tortuous retinal veins, central retinal vein occlusion, central retinal artery occlusion, acute macular neuroretinopathy (AMN), paracentral acute middle maculopathy, acute retinal necrosis, endophthalmitis, optic neuritis, and others.

These may not be due to the virus but as a result of systemic complications that this virus could cause. In the hundreds of millions of circumstances of COVID-19 infection is observed worldwide, findings supporting direct retinal damage (apart from vascular damage) from the virus haven’t been described.

Retinal macro and microvascular damage4 observed in patients with COVID-19 may very well be related to systemic thromboembolism, other systemic morbidities, or to the impact of the virus on retinal vessels. COVID-19 infection can also be related to an enormous dysregulation of the humoral immune system characterized by the looks of potent autoantibodies reacting towards a variety of soluble and tissue-specific proteins, which additionally would possibly contribute to ocular disease.



What about COVID-19 vaccination and the retina? There have been anecdotal circumstances of adverse retinal ischemic events offered at conferences and undoubtedly awaiting publication.

For instance, we just lately noticed a middle-aged woman with diabetes and hypertension with a distant branch retinal artery occlusion in the left eye. Optical coherence tomography on the precise showed AMN.


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Two weeks prior, she had obtained a Johnson & Johnson COVID-19 vaccination. Is the AMN from the vaccination or associated with her systemic vasculopathy? When uncommon retinal findings (eg, AMN) are noted in association with a more common event (in this case COVID-19 vaccination), the findings could also be unrelated.

Nevertheless, there are conditions where one can suspect the associations have a real cause-and-effect relationship. Put up–adenovirus vector vaccination (Johnson & Johnson, AstraZeneca), patients can have doubtlessly life-threatening cerebral venous sinus thrombosis (CVST).5

These patients often have thrombocytopenia, which may be very hardly ever related to thrombosis. Whereas CVST and thrombocytopenia after COVID-19 vaccination are extremely rare, it’s much more common than in the general population.



In these patients with CVST, the presence of platelet-activating autoantibodies against platelet issue 4 causes multicellular activation of coagulation. It mimics autoimmune heparin-induced thrombocytopenia. This syndrome is now referred to as vaccine-induced immune thrombotic thrombocytopenia.

It usually occurs inside the first 3 weeks following vaccination, principally in younger women. Antiplatelet factor 4 antibodies are pathognomonic for vaccine-induced immune thrombotic thrombocytopenia. As of April 4, 2021, 169 circumstances of CVST have been reported in 34 million people vaccinated with AstraZeneca in the European Union and the UK, corresponding to a reporting rate of 5 circumstances per million vaccinated adults.6

As of April 12, 2021, 6 circumstances of CVST with thrombocytopenia were reported after 6.86 million Johnson & Johnson doses, comparable to a reporting rate of 0.87 circumstances per million doses.7 A causal relationship with vector-based vaccination thus is considered believable by regulatory agencies. In contrast to vector-based vaccines, CVST with thrombocytopenia has not occurred after 183 million messenger RNA (mRNA) COVID-19 vaccine doses were administered.

As reviewers for journals and individuals in conferences, we’re observing patients presenting who’ve had COVID-19 vaccination with attainable secondary retinal findings (eg, AMN or paracentral acute center maculopathy). Vaccines have completely different mechanisms of inducing immunity and completely different adverse event profiles.

COVID-19 vaccines differ when it comes to genetic assemble (mRNA vs DNA) or vector virus (human replication-incompetent adenovirus [Ad26.COV2S] for Johnson & Johnson vs chimpanzee replication incompetent adenovirus [ChAdOx1] for AstraZeneca). With the adenovirus vector vaccines, DNA encoding the spike protein is delivered and the immune system generates antibodies to this protein.

With the Pfizer and Moderna vaccines, the mRNA for the spike protein is encapsulated in liposomes and endocytosed into the muscle cell. The mRNA is translated into S protein in the host cell cytosol. This protein is then expressed on the cell floor the place it induces an immune response. In contrast to all different vaccines, the coding sequence SARS-CoV-2 S immunogen in the AstraZeneca vaccine has not been modified to stabilize and mitigate the shedding of the expressed S protein.8

Thus, it’s possible that expressed S protein in the circulation after AstraZeneca vaccination can induce a proinflammatory/procoagulant response or direct disturbance of endothelial cell integrity.

More than 1.5 billion doses of COVID-19 vaccinations have been administered worldwide and sure will save hundreds of 1000’s if not millions of lives. How does one decide if retinal abnormalities are related to the vaccination after they seem soon after inoculation?

These various events (eg, AMN) are observed often in unvaccinated patients; is the vaccine causative or coincidental? If these circumstances are submitted to a journal, should such articles be published? Should a reader settle for that the findings are causally associated with COVID-19 vaccination?

The establishment of a causal relationship between the vaccine and an observed pathology will remain stimulating and should be guided by the scientific/medical principles of assessing whether the commentary is unquestionable, most likely, presumably, unlikely, or not associated.



Since vaccinations don’t contain an intact virus, the mechanism of ocular disease can be an immunologic response to the spike antigen, different viral antigens, or to components of a chimpanzee or human adenovirus. Molecular mimicry (the structural similarities of SARS-CoV-2 or human or chimpanzee adenovirus components) and self-antigens might contribute to the pathogenesis of any retinal pathologies.

Surveillance for adverse events following vaccinations is required in clinical trials and customary adverse events are detected. When a much larger variety of vaccinations are done, it is rather tough to rule out coincidence for rare events.

If unique facets (eg, age, sex, systemic findings, eye findings, and different morbidities) of the adverse events are noted, then causation should be suspected. If the pathophysiology of the vaccine response fits with the pathology, then causation will be suspected. Could the adenovirus vaccines, which might trigger thrombosis, vasculitis, and morbidities, trigger ocular adverse events, or are the events coincidental?

Are the events described by Pichi et al with an inactivated viral vaccine coincidental or related to the vaccine? They’re one piece of proof that now ought to await affirmation or refutation.

Reference

  1. Pichi  F, Aljneibi  S, Neri  P, Hay  S, Dackiw  C, Ghazi  NG.  Association of ocular adverse events with inactivated COVID-19 vaccination in {patients} in Abu Dhabi.  JAMA Ophthalmol. Published online September 2, 2021. doi:10.1001/jamaophthalmol.2021.3477
  2. Mallapaty  S.  China’s COVID vaccines are going global—but questions remain.   Nature. 2021;593(7858):178-179. doi:10.1038/d41586-021-01146-0
  3. Turecek  PL, Peck  RC, Rangarajan  S,  et al.  Recombinant ADAMTS13 reduces abnormally up-regulated von Willebrand factor in plasma from {patients} with severe COVID-19.   Thromb Res. 2021;201:100-112. doi:10.1016/j.thromres.2021.02.012
  4. Turker  IC, Dogan  CU, Guven  D, Kutucu  OK, Gul  C.  Optical coherence tomography angiography findings in {patients} with COVID-19.   Can J Ophthalmol. 2021;56(2):83-87. doi:10.1016/j.jcjo.2020.12.021
  5. Cines  DB, Bussel  JB.  SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia.   N Engl J Med. 2021;384(23):2254-2256. doi:10.1056/NEJMe2106315
  6. European Medicines Agency. Vaxzevria: further advice on blood clots and low blood platelets. Accessed August 3, 2021. https://www.ema.europa.eu/en/news/vaxzevria-further-advice-blood-clots-low-blood-platelets
  7. Centers for Disease Control and Prevention. Joint CDC and FDA statement on Johnson & Johnson COVID-19 vaccine. Accessed August 3, 2021. https://www.cdc.gov/media/releases/2021/s0413-JJ-vaccine.html
  8. Choe  H, Farzan  M.  How SARS-CoV-2 first adapted in humans.   Science. 2021;372(6541):466-467. doi:10.1126/science.abi4711

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