Acute corneal allograft rejection following SARS-CoV-2 vaccination-A systematic review

All documented cases of acute corneal allograft rejection following SARS-CoV-2 vaccination were examined, to characterize possible risk factors and graft outcomes. Comprehensive search (4 electronic databases: PubMed, CENTRAL, ClinicalTrials.gov, Google Scholar, plus manual search in articles' reference lists) until March 1st 2022 to identify studies reporting acute corneal allograft rejection following SARS-CoV-2 vaccination; study protocol was developed in line with PRISMA statement. We analysed demographics, allograft type, rejection prophylaxis regime at the time of vaccination, transplantation-to-vaccination time (G-Vt), vaccination-to-immune reaction onset time (V-Rt), management, best-corrected visual acuity before and after rejection, and graft survival. Of 169 titles/abstracts screened, 16 studies (n  = 36 eyes) met the inclusion criteria. Fourteen eyes (38.9%) had received >1 graft, and 11.1% of cases had history of immune reactions; 52.9% of cases occurred after the first dose. Median (P25-P75) G-Vt was 48 (10-78) months; median V-Rt was 9 (7-14) days. In eyes with resolved rejection, median time-to-resolution was 3 (1-4) weeks. Four eyes (11.1%) had partial resolution of corneal decompensation, and 5 grafts (13.9%) failed. Acute corneal allograft rejection after SARS-CoV-2 vaccination is a rare event, but may occur any time post-keratoplasty. Early recognition and prompt, aggressive treatment is warranted to optimize vision and graft survival. Well-known risk factors for rejection may be confounding factors, including the high proportion of cases with a history of previous grafts and the rejection prophylaxis regimes at the time of vaccination. Increasing immunosuppressants in the peri-vaccination period may decrease the risk of immune reactions, especially in high-risk cases.