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  • Comprehensive Ophthalmology, Cornea/External Disease

    Review of: Characteristics of endothelial corneal transplant rejection following immunization with SARS-CoV-2 messenger RNA vaccine

    Phylactou M, Li J, Larkin D. British Journal of Ophthalmology, April 2021

    This study describes 2 cases of corneal allograft rejection after receiving the COVID-19 vaccine (BNT162b2; Pfizer-BioNTech). Prior to receiving the vaccine, each patient underwent Descemet's membrane endothelial keratoplasty (DMEK) for Fuchs endothelial corneal dystrophy (FECD).

    Case 1

    A 66-year-old woman received the first dose of COVID-19 vaccine 14 days after a unilateral DMEK transplant combined with phacoemulsification and IOL implantation. Twenty-one days after surgery—7 days after vaccination—she presented with acute onset of blurred vision, redness and photophobia. The patient had complied with the prescribed topical medication regimen (topical dexamethasone 0.1% every 2 hours for 2 weeks, followed by 4 times daily). Her BCVA was 20/120 in the right eye.

    Slit-lamp examination revealed a well-positioned posterior chamber IOL, but there was moderate conjunctival injection, diffuse corneal edema, fine keratic precipitates restricted to the inferior donor endothelium and anterior chamber (AC) inflammation. The left eye showed no inflammation and dilated fundoscopy was normal in both eyes. Anterior segment OCT confirmed a full-graft attachment and showed that central corneal thickness significantly increased from 525 µm to 652 µm between days 7 and 21. To treat acute endothelial graft rejection, physicians increased the frequency of topical steroid to hourly. By follow-up day 3, symptoms and signs of inflammation began to resolve and by 4 weeks, visual acuity was 20/20 and there were no signs of active inflammation.

    Case 2

    Three weeks after the second dose of COVID-19 vaccine, an 83-year-old woman with bilateral DMEK transplants—received 3 and 6 years earlier in the left and right eyes, respectively—developed simultaneous acute endothelial rejection in both eyes. Her symptoms included sudden onset of bilateral blurred vision, pain, photophobia and redness. Five months earlier, BCVA was 20/20 in both eyes and topical steroid medication had been discontinued. At presentation, BCVA was 20/80 and 20/40 in the right and left eyes, respectively.

    Slit-lamp examination demonstrated bilateral circumcorneal injection, keratic precipitates and greater AC inflammation in her right eye. Dilated fundoscopy was normal. Central corneal thickness was 660 µm in the right eye and 622 µm in the left. The patient was treated with hourly steroid drops. By follow-up day 7, signs of inflammation were reduced, both grafts were functioning well and BCVA had improved to 20/20 in both eyes. The frequency of topical dexamethasone was reduced.


    Although there is no definitive evidence that COVID-19 vaccination led to corneal endothelial transplant rejection, the temporal association and the occurrence of simultaneous bilateral rejection—which is rarely seen in clinical practice—suggest a causal relationship. The authors hypothesize that the host antibody response might have triggered the allogeneic response.

    Vaccine trials have shown that the BNT162b2 vaccine induces both adaptive humoral and cellular immune responses. Twenty-one days after vaccination, all study participants had elevated levels of anti-spike neutralizing antibody titers, antigen-specific CD4+ and CD8+ T cell responses, and proinflammatory cytokines such as interferon gamma (IFNγ). IFNγ-producing CD4+ T helper 1 cells are important in corneal allograft rejection. Cross-reactivity between the virus antigen-specific T cells and the HLA antigen-disparate corneal allograft endothelial cells may have contributed to the graft rejection in these 2 patients.

    Clinical significance

    This study is the first evidence of a temporal association between corneal transplant rejection after COVID-19 mRNA vaccination and the first case reports of DMEK rejection following any immunization. Patients need to be informed of the symptoms and signs of rejection that require immediate medical attention. Clinicians and patients should be aware of this potential risk and consider vaccination before planned nonurgent keratoplasties. In those who already have corneal transplants, it may be beneficial to either increase the frequency of existing steroid regimens or avoid reducing treatment around the time of vaccination. When patients present with signs of transplant rejection, physicians should inquire about a history of vaccination and report temporal associations to the relevant agencies. As both patients were successfully treated with topical corticosteroids, the findings in this paper should not deter administration of the COVID-19 vaccination, because early recognition and prompt treatment of rejection can yield positive outcomes.