As more patients are vaccinated against COVID-19, cornea surgeons are encountering a late postoperative complication that heretofore has been rare: postvaccination corneal allograft rejection.
The first publication of case reports came in April, from clinicians at Moorfields Eye Hospital in London.1 Prior to that, anecdotal reports of COVID vaccine–associated rejection episodes began surfacing during the first few months of 2021, and some of these likely will be the subjects of additional peer-reviewed papers this year, said Bennie H. Jeng, MD, at the University of Maryland School of Medicine in Baltimore.
“This is an issue around the world,” Dr. Jeng said. “On the Kera-net listserv of the Cornea Society, more and more cornea surgeons are reporting this with the COVID vaccinations.”
ACUTE EARLY REJECTION. Endothelial rejection occurred seven days after this patient received her COVID vaccination.
Need for ongoing vigilance. Maria Phylactou, MD, who coauthored the Moorfields paper, and Dr. Jeng agreed that it is important for ophthalmologists in the COVID era to be vigilant for this. Even eyes that have been doing well for years following a transplant can be affected, so patients should be alerted to watch for rejection signs, they said.
“What we’d like to highlight is, first, that this is a very rare event, but it definitely can occur—and second, that early recognition and early intensive treatment are essential,” Dr. Phylactou said.
Case examples. The first affected patient at Moorfields had a successful, unilateral keratoplasty with full graft attachment, a clear cornea, and best-corrected visual acuity (BCVA) of 6/6 (20/20) at postsurgical day 7. Fourteen days after the transplant, she received the first injection of the Pfizer-BioNTech vaccine. A week later, her VA decreased, and she developed other signs of acute rejection.
The second patient had bilateral grafts that had been functioning well for six years and three years. Three weeks after her second dose of the Pfizer-BioNTech vaccine, she presented with acute graft rejection in both eyes.
Treatment consisted of one week of hourly dosing with corticosteroid eyedrops (dexamethasone), followed by judicious tapering. Both patients recovered their previous visual acuity, the researchers reported.
An issue of timing? Although a causal link is not proven, the timing of vaccination and development of rejection signs suggested to Dr. Phylactou and her colleagues that the patients’ immune responses might have been injuring the inner surface of the donor corneal tissue, she said.
“In the first case, you could see the rejection happen very quickly, at the time when the immune system would be responding to the vaccine. In the second case, the patient had a serious reaction bilaterally, which is extremely rare, considering that she had a different donor for each eye. So that makes the probability of a causal association with the vaccination even higher,” she said.
Dr. Jeng noted that in the cases that he has heard about anecdotally, rejection seems to occur one to two weeks after the second vaccine dose, which suggests the body’s immune response is the culprit. “That makes sense, right? Because the second shot is the one exposing the patient to the antigens that the body is seeing for the second time,” he said.
Not a brand-new issue. The literature contains a few reports over the last three decades of vaccine-related graft rejection, Dr. Jeng said. He is a coauthor of a study slated to be published in Cornea; when he and his colleagues surveyed cornea surgeons before the pandemic, they found that a fifth of the respondents had seen rejection associated with herpes zoster or influenza vaccines.2
Advice to patients. Neither Dr. Phylactou nor Dr. Jeng would discourage patients from getting the COVID vaccine.
However, postponing nonurgent keratoplasties until a few months after vaccination might be worthwhile, they said. If this is not possible, patients should be advised to seek treatment early if signs of rejection occur, they said. And those with existing corneal grafts also should be reminded of this, Dr. Jeng added.
1 Phylactou M et al. Br J Ophthalmol. Published online April 28, 2021.
2 Lockington D et al. Cornea. 2021. In press.
Relevant financial disclosures—Drs. Jeng and Phylactou: None.
For full disclosures and the disclosure key, see below.
Full Financial Disclosures
Dr. Cheng Singapore National Medical Research Council: S.
Dr. Jeng EyeGate Pharmaceuticals: O; GlaxoSmithKline: C; Kedrion: C; Merck: C; Sanofi: C; Santen: C.
Dr. Kaiser Aerie: C; Aerpio: C; Allegro: C; Allergan: C; Bayer Healthcare Pharmaceuticals: C,L; Biogen: C; Boehringer Ingelheim: C; Clearside: C; Eyevensys: C; Formycon: C; Galecto: C; Galimedix: C; Genentech: C; Glaukos: C; iRenix: C; Iveric Bio: C,O; jCyte: C; kala: C; Kanghong: C; Kodiak: C; Novartis: C,L; Omeros: C; Opthea: C; Oxurion: C; Regeneron: C,L; RegenxBio: C; Retinal Sciences: C,O; Santen: C; Stealth: C; Verana: O.
Dr. Phylactou None.
||Consultant fee, paid advisory boards, or fees for attending a meeting.
||Employed by a commercial company.
||Lecture fees or honoraria, travel fees or reimbursements when speaking at the invitation of a commercial company.
||Equity ownership/stock options in publicly or privately traded firms, excluding mutual funds.
||Patents and/or royalties for intellectual property.
||Grant support or other financial support to the investigator from all sources, including research support from government agencies (e.g., NIH), foundations, device manufacturers, and/or pharmaceutical companies.
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