Though relatively uncommon, case reports have documented the incidence of corneal graft rejection following vaccination — most commonly with the influenza vaccine, though also with tetanus toxoid, hepatitis B, herpes zoster, and, most recently, the SARS-CoV-2 (COVID-19) vaccine.^1-7

Below, I discuss the article “Keratoplasty Rejection Risk Associated with Recent Vaccination — the Pragmatic Approach,” which provides insights regarding the risk of keratoplasty rejection post-COVID-19 vaccination.¹

Overview

In this article, the author highlights the importance of recognizing the association of episodes of keratoplasty rejection following vaccination, especially in light of global vaccination efforts for COVID-19.¹ Though some studies contradict these associations, these cases and anecdotal accounts from colleagues deserve acknowledgement. ^1,4,8

The author writes that prior to the COVID-19 pandemic, he surveyed 142 surgeons regarding whether they would advise a keratoplasty patient to refuse a vaccine.¹ Most said they would never advise this.¹ Surgeons did express heightened concern in patients who underwent recent transplantation, live herpes zoster vaccination, and high-risk PK, due to these conditions’ common association with graft rejection. Endothelial keratoplasty patients seem to have a low risk of rejection following vaccination.^1-3 Cases of documented unilateral and bilateral simultaneous endothelial graft rejection following COVID-19 vaccination also warrant concern.^1,2,6,7

An important and pragmatic recommendation is for corneal societies to ask their members to keep a record of such cases — with a view to combine cases into publications.¹ This could provide more evidence-based guidelines for corneal specialists and their patients in going forward.

Value

Keratoplasty is performed widely each year, with great success rates over other types of organ transplantation, largely thought to be due to ocular immune privilege.^1,4,9-11 However, this privilege is not absolute; patients and practitioners alike should still be vigilant regarding graft rejection.^1,4,8-11

In the absence of clear cause-and-effect evidence, it is suggested that a practical first step regarding possible graft rejection in association with vaccination is education.^1-7 Specifically, patients undergoing corneal transplantation should be counseled preoperatively regarding signs and symptoms of graft rejection, as well as potential rejection triggers.^1-7 This education should not encourage vaccine hesitancy, especially given the current worldwide goal of controlling COVID-19.^1-7

Also, it is important to educate patients that early recognition of graft rejection often leads to prompt and successful treatment, which may consist solely of topical steroid drops.^1-7 Some surgeons may choose to prophylactically increase topical steroid therapy pre- and post-vaccination. This is something we do in our practice, in concert with graft rejection and inflammation monitoring.^1-7 The approach to vaccination in a keratoplasty patient requires a careful consideration of risks, benefits, and alternatives — with, oftentimes, the benefits of vaccination far outweighing the risks. CP

References

1. Lockington D. Keratoplasty rejection risk associated with recent vaccination—the pragmatic approach. Cornea. 2021;40(11):1374-1376.
2. Sales CS. Covid vaccination, corneal transplants, steroid drops, before and after. The Corneal Dystrophy Foundation. (Accessed March 2, 2021.) https://www.cornealdystrophyfoundation.org/covid-vaccination-corneal-transplants-steroid-drops-after
3. Miedziak AI, Tambasco FP, Lucas-Glass TC, Rapuano CJ, Laibson PR, Cohen EJ. Evaluation of triggers for corneal graft rejection. Ophthalmic Surg Lasers. 1999;30(2):133-139.
4. Stulting RD, Lass JH, Terry MA, et al. Factors associated with graft rejection in the Cornea Preservation Time Study. Am J Ophthalmol. 2018;196:197-207.
5. Wertheim MS, Keel M, Cook SD, Tole DM. Corneal transplant rejection following influenza vaccination. Br J Ophthalmol. 2006;90(7):925-926.
6. Nioi M, d’Aloja E, Fossarello M, Napoli PE. Dual corneal-graft rejection after mRNA vaccine (BNT162b2) for COVID-19 during the first six months of follow-up: case report, state of the art and ethical concerns. Vaccines. 2021;9(11):1274.
7. Rallis K, Ting DSJ, Said DG, Dua HS. Corneal graft rejection following COVID-19 vaccine. Eye. 2021; 23:1-2
8. Niderkorn J. Corneal transplantation and immune privilege. Int Rev Immunol. 2013;32(1):57-67.
9. Lass JH, Szczotka-Flynn L, Ayala A, et al. Cornea preservation time study: methods and potential impact on the cornea donor pool in the United States. Cornea. 2015;34(6):601-608.
10. Zhou X, Ye Q. Cellular immune response to COVID-19 and potential immune modulators. Front. Immunol. 2021;12:646333.
11. Gain P, Jullienne R, He Zhigou, et al. Global survey of corneal transplantation and eye banking. JAMA Ophthalmol. 2016;134(2):167-173.

DR. NATTIS is a cornea, cataract, and refractive surgeon and director of clinical research at SightMD, in Babylon, NY, and an associate professor of ophthalmology and surgery at the New York Institute of Technology – College of Osteopathic Medicine in Old Westbury, NY.