Assessment of Corneal Graft Rejection Rates Following Partial Endothelial Keratoplasty in COVID-19 Vaccinated Patients
Muhammad Hamza *3, Bhagyashree Natu 1, Muhammad Farrukh Siddiqui 2, David Anderson 1, Aristides Konstantopoulos 1, Prof. Parwez Hossain 1
*Correspondence to: Muhammad Hamza. University Hospital Southampton NHS Trust, England and Liaquat National Hospital and Medical, College, Karachi, Pakistan.
Copyright
© 2024 Muhammad Hamza. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 08 January 2024
Published: 31 January 2024
Introduction
The emergence of COVID-19, caused by the SARS-CoV-2 virus at the end of 2019 triggered an explosion of vaccine development. By 24 September 2020, a staggering number of vaccines (more than 200) had started preclinical development, of which 43 had entered clinical trials. Vaccines have been widely considered as part of the escape plan to enable the return to earlier patterns of working, schooling, and socializing (ref. 1). Within less than a year time some very promising COVID-19 vaccines were developed at an unprecedented speed and are now being deployed via emergency use authorization for immunization (ref. 1,2).
Corneal transplantation is the oldest, most common, and arguably the most successful form of solid tissue transplantation. In terms of technique, descemet membrane endothelial keratoplasty (DMEK) is a highly effective form of partial corneal transplant that provides the greatest chance of achieving 20/20 vision and has the quickest recovery period compared to other techniques that replace the innermost layer of the cornea's endothelium (ref. 3). Allogenic tissue or solid organ transplantations introduce genetically different tissues to the recipient, which may cause a T cell-mediated immune response that leads to rejection and destruction of the transplant (ref. 4). Partial endothelial keratoplasty has a low graft rejection rate because of ocular immune privilege, which can be compromised by increased immune dysregulation (ref. 5). There have been isolated case reports of graft rejection following Covid -19 vaccine. So far 11 cases of acute graft rejection have been reported in the literature (ref. 6–9). Corneal graft rejection has also been reported following Influenza, hepatitis b vaccine, and yellow fever vaccine (ref. 10–12). There are no studies to our knowledge that show graft reflection after partial endothelial keratoplasty.
We, therefore, did a study involving 208 patients to investigate the incidence of graft rejection following the COVID-19 vaccine.
Methods
Patient Identification
We identified patients who had undergone corneal transplant surgery and subsequently received the COVID-19 vaccine. Patients were identified through electronic medical record searches and were included in the study if they met the following criteria: had received a corneal transplant, had received two doses of a COVID-19 vaccine, and had a documented telephonic follow-up after receiving the vaccine.
Data Collection:
This study involved the collection and analysis of data from 208 patients who had undergone partial endothelial keratoplasty and received two doses of COVID-19 vaccine. Participants were evaluated using a questionnaire designed to assess symptoms of graft rejection, including foreign body sensation, photophobia, redness, blurry vision, discomfort, and attendance in the eye emergency department for any concerns. The questionnaire was approved by a panel of five experienced ophthalmologists.
Ethical considerations
The ethical considerations for the study include obtaining verbal consent from patients over the telephone, ensuring the privacy and confidentiality of their personal information by storing the data in Medisoft software and in Excel sheet form, and providing access to the data only to the authors involved in the study.
The verbal consent process was implemented to ensure that patients were fully informed about the study and had the opportunity to ask any questions before agreeing to participate. The use of Medisoft software and Excel spreadsheets for data storage and management was done to protect the privacy and confidentiality of the patients’ personal information, and access to the data was restricted to the authorized authors to prevent any unauthorized use or disclosure of the data.
Results
Out of 208 patients 152 were male and 56 were female. 190 had AstraZeneca (adenovirus vector vaccine) and 18 had Pfizer (mRNA vaccine). The range of age 69-90 years with mean age being 77 years. The telephonic appointment was 4-8 weeks following the second covid-19 vaccine. None of our patients complained of any symptoms of acute graft rejection.
After undergoing partial endothelial keratoplasty, none of our patients exhibited symptoms or indications of graft rejection during the specified period when attending the eye clinic or seeking emergency eye care. Additionally, none of our patients received a diagnosis of graft rejection elsewhere.
Discussion
Absence of blood and lymphatic vessels in the central cornea gives it [lymph] angiogenic privilege (ref. 4) thus, a low rate of graft rejection. However, any systemic immune dysregulation may compromise corneal ocular immune privilege and increase the patient’s susceptibility for rejection. In some COVID-19 patients symptoms gradually worsen within a week or more after developing symptoms, suggesting that severe COVID-19 pathogenesis could be mediated by a dysregulated immune response (ref. 13).
COVID-19 vaccines have been shown to induce SARS-CoV-2 neutralizing antibodies and elicit strong Th1-biased CD4+ responses in human CD4+ Th1 cells have been shown to be the main mediators of corneal graft rejection hence the postulation of rejection following Covid-19 vaccine (ref. 8,14).
Rejection following a vaccination is a rare event. In a study to investigate attitudes of corneal specialist if patients with keratoplasty sought advice regarding common vaccinations nearly 45.9% of the respondent do not alter any management in setting of zoster or influenza vaccine. While 26.2 % would increase frequency of topical steroids and 22.2 % would recommend delay to vaccinations (ref. 9).
Our research did not identify any cases of partial endothelial keratoplasty corneal graft rejection after the
first or second dose of the COVID-19 vaccine. However, Jordan CS et al reported that up to 35% of cases of endothelial keratoplasty rejection may not show any symptoms and may only be detected during routine checkups (ref. 15). It should be noted that all reported cases of corneal graft rejection following COVID-19 vaccination were associated with symptoms, according to anecdotal evidence.
Limitations of the study include reliance solely on a telephonic survey to inquire about common symptoms related to graft rejection and any hospital visits for eye problems. This approach may not have captured all relevant information, such as subtle changes in visual acuity or symptoms that patients may have deemed too minor to report. Additionally, the survey relied on patients' self-reported symptoms, which may have been subject to recall bias or misinterpretation of symptoms. As such, the results of this study should be interpreted with caution and validated by further research using more comprehensive and objective measures to evaluate graft rejection and other ophthalmological outcomes.
Conclusion
Covid-19 vaccine related Corneal graft rejection is anecdotal but some cases have been reported even 24 months after the Vaccine (ref. 16), hence with the rampant vaccination we need to keep our patients educated regarding the common symptoms of corneal graft rejection and to seek urgent eye care in event of any symptoms.
So far 69.3% of the world population has received at least one dose of a COVID-19 vaccine. 13.23 billion doses have been administered globally (ref. 17). We recommend a larger trial to establish any causal relationship with covid vaccine and graft rejection.
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