Corneal Transplants and COVID Vaccines

Corneal transplantation is the most commonly performed and the most successful allogenic transplant worldwide. Corneal transplantation can restore vision to a patient with a damaged cornea and help relieve symptoms of progressive corneal diseases, such as keratoconus or Fuchs’ dystrophy. These procedures were performed during the ongoing COVID-19 pandemic, and data are beginning to be published on the effects of COVID-19 infection and COVID-19 vaccination on transplant results.

Corneal transplant surgical procedure

There are various corneal transplants based on the amount of tissue replaced during the procedure and whether the anterior or posterior corneal layers need to be removed.

The main categories of corneal transplants are:

Penetrating keratoplasty (PK)
Endothelial keratoplasty, of which there are two subtypes:
- Descemet stripping automated endothelial keratoplasty (DSAEK)
- Descemet membrane endothelial keratoplasty (DMEK)
Superficial anterior lamellar keratoplasty (SALK)
Deep anterior lamellar keratoplasty (DALK)
Artificial corneal transplant (keratoprosthesis)

PK is a full-thickness corneal transplant. The ophthalmologist will trephine the patient’s cornea, and the donor cornea will be dissected to fit and placed into the opening. The donor cornea is then sutured into place, and these sutures may be removed later. Also known as an “open-sky” technique, since the globe is “open” to the external environment during surgery, PK provides a surgical approach to replace all the layers of the cornea.

DSAEK and DMEK are partial-thickness corneal surgical techniques and involve removing diseased tissue from the posterior lamellar layers of the cornea and replacing them with donor tissue. DSAEK involves the selective removal of Descemet’s membrane and endothelium from the patient (approximately one-third of the cornea is removed), followed by transplantation of donor corneal endothelium and corneal stroma.

Contrasting with DSAEK, DMEK partial-thickness transplantation is more selective and only adds a new Descemet’s membrane and endothelium without a donor layer of the corneal stroma.

Like DSAEK and DMEK, SALK and DALK both entail removing the diseased tissue, except these two procedures involve tissue from the anterior corneal layers rather than the posterior. The amount of damage determines the procedure used there is to the cornea. SALK removes less than one-third of the anterior corneal stroma and is used when more superficial damage. DALK is preferred when the damage goes deeper into the anterior corneal stroma.

Artificial corneal transplantation is usually only utilized when previous transplant methods have failed. The most commonly used is the Boston Keratoprosthesis, which is a collar button designed for keratoprosthesis. The donor corneal tissue is sandwiched between two plates that snap together and are then sutured into the eye.

Signs of transplant rejection

Transplant rejection can occur at either the epithelial, endothelial or stromal layer. Patients experiencing either epithelial or stromal rejection may be asymptomatic or simply present with mild ocular discomfort. In contrast, patients with endothelial rejection usually present with visual disturbance and iritis-related symptoms. Rejection can be treated, and the goal is to reverse rejection at the earliest time possible.

In many cases, the administration of a topical corticosteroid successfully reverses transplant rejection. In cases in which topical steroid fails to reverse rejection, it is likely to be due to delay in recognition and initiation of treatment resulting in significant donor endothelial cell loss. In other instances, failure to reverse rejection may be due to the inability of topical steroids to change effector components of the allogeneic response.

COVID-19 infection and transplant results

Immune system dysregulation in primary SARS-CoV-2 infection can incite fatal immune responses. The host immune system becomes hyperactive, causing an excessive inflammatory response known as a “cytokine storm,” which releases many pro-inflammatory cytokines. The primary pathological correlations of the cytokine storm are lung injury, multi-organ failure, and unfavorable prognosis of COVID-19.

Based on early cases, this proinflammatory state can also contribute to a breach of the immune privilege of the cornea, leading to transplant rejection.

A 32-year-old man developed an episode of acute graft rejection coinciding with a COVID-19 infection. The patient received a penetrating keratoplasty six years prior. Blood tests confirmed that this patient was in the cytokine storm phase of disease at the time of the graft rejection. In another case involving a 31-year-old woman who began experiencing symptoms of acute corneal endothelial graft rejection 3 months after an uncomplicated penetrating keratoplasty also coincided with a subsequent diagnosis of COVID-19.

While these findings are certainly of interest to the medical community, two reported cases are not a large enough sample size to make factual statements regarding the risk of COVID-19 infection and corneal transplant rejection.

COVID-19 vaccination and transplant results

With the COVID-19 vaccine becoming widely available in the United States, there has been significant pushback regarding the possible risks of receiving the vaccine.

In a report published in January 2022, four acute corneal transplant rejection cases were reported in association with the COVID-19 mRNA vaccine:

One patient received DMEK transplantation 6 months prior and presented with acute graft rejection 3 weeks after their first vaccine dose.
The second patient had undergone penetrating keratoplasty three years earlier and presented with acute endothelial rejection 9 days after their second vaccine dose.
The third patient had a prior DSAEK procedure and began experiencing symptoms of endothelial graft rejection 2 weeks after their second vaccine dose.
The fourth patient had previously undergone penetrating keratoplasty and presented with signs of endothelial graft rejection 2 weeks after their second vaccine dose.

In all four cases, topical corticosteroids were administered, and symptoms of transplant rejection improved.

Similar to the cases involving COVID-19 infection and transplant rejection, four cases are not a large enough sample size to set a precedent regarding vaccination in corneal transplant patients moving forward.

Takeaway points

Although these cases are not a statistically considerable enough sample size to create new policies surrounding COVID-19 and vaccination concerning corneal transplant patients, there are certainly lessons an ophthalmologist, eyecare provider, or any other medical professional can gain from them. While a patient contracting COVID-19 cannot be controlled, physicians can recommend COVID-19 vaccination before a corneal transplant procedure to lower the risk of possible graft rejection later on.

More data should be released on the potential effects of COVID-19 infection and vaccination on corneal transplants as time goes on.

References

“Cornea Transplant - Mayo Clinic.” Mayo Clinic - Mayo Clinic, 22 Dec. 2020, https://www.mayoclinic.org/tests-procedures/cornea-transplant/about/pac-20385285#:~:text=A%20cornea%20transplant%20is%20most,cornea%20that%20bulges%20outward%20(keratoconus).
Jin, Sierra, and Viral Juthani. “Acute Corneal Endothelial Graft Rejection With Coinciding COVID-19 Infection - PubMed.” PubMed, Cornea, Jan. 2021, https://pubmed.ncbi.nlm.nih.gov/32889957/.
Mahabadi, Navid. “Corneal Graft Rejection - StatPearls - NCBI Bookshelf.” National Center for Biotechnology Information, StatPearls, 19 July 2021, https://www.ncbi.nlm.nih.gov/books/NBK519043/.
Phylactou, Maria. “Characteristics of Endothelial Corneal Transplant Rejection Following Immunisation with SARS-CoV-2 Messenger RNA Vaccine - PubMed.” PubMed, The British Journal of Opthalmology, July 2021, https://pubmed.ncbi.nlm.nih.gov/33910885/.
Ragab, Dina. “The COVID-19 Cytokine Storm; What We Know So Far.” PubMed Central (PMC), Frontiers in Immunology, 16 June 2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308649/#:~:text=COVID%2D19%20infection%20is%20accompanied,in%20an%20excessive%20inflammatory%20reaction.
Shah, Amar. “Acute Corneal Transplant Rejection After COVID-19 Vaccination - PubMed.” PubMed, Cornea, Jan. 2022, https://pubmed.ncbi.nlm.nih.gov/34620770/#:~:text=Conclusions%3A%20These%20cases%20suggest%20acute,of%20clinical%20signs%20and%20symptoms.
Singh, Garima, and Umang Mathur. “Acute Graft Rejection in a COVID-19 Patient: Co-Incidence or Causal Association? - PubMed.” PubMed, Indian Journal of Ophthalmology, Apr. 2021, https://pubmed.ncbi.nlm.nih.gov/33727473/.