Corneal Graft Rejection

Updated: Oct 16, 2018
  • Author: Michael Taravella, MD; Chief Editor: Hampton Roy, Sr, MD  more...
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Overview

Background

Although described for more than 100 years, corneal transplantation has become increasingly common since the 1960s. In 2016, approximately 83,000 corneal transplantations were performed in the United States. [1] Corneal graft rejection is the most common cause of graft failure in the late postoperative period. [2]

Examples of corneal graft rejection are shown in the images below.

This severely vascularized cornea would be at high This severely vascularized cornea would be at high risk for graft rejection following a penetrating keratoplasty. This patient experienced Stevens-Johnson syndrome.
This is an example of an acute graft rejection epi This is an example of an acute graft rejection episode. Note the graft edema, Descemet folds, and keratic precipitates.
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Pathophysiology

Corneal transplantation has a high success rate in part because of the relative immune privilege of the cornea. The cornea is avascular, limiting access of lymphocytes and other immune responsive cells. [3] There are no associated lymph nodes; therefore, the opportunity for presentation of foreign antigen to antigen-presenting cells and T cells is also limited. The cornea expresses MHC antigens to a lesser extent than other tissues, contributing to immune privilege. However, this can be compromised by prolonged inflammation, extensive vascularization, and other factors, resulting in rejection.

The term graft rejection refers to the specific immunologic response of the host to the donor corneal tissue. Because it is a specific process, it should be distinguished from other causes of graft failure that are not immune mediated. A corneal graft that has suffered this immunologic response may or may not ultimately fail. Some physicians distinguish between graft reaction, which is reversible with medical therapy, and graft rejection, in which the immunologic end stage has been reached and the process is irreversible. Other physicians simply use graft rejection to refer to this immunologic process at any stage of its development, noting that some cases progress to graft failure because of rejection. This second terminology is used in this article because it is in line with terminology used in other types of organ transplantation.

Furthermore, at the time of presentation, determining with certainty whether an immune process is reversible is impossible.

Ritter et al discuss the need for further study of the genetic modification of corneal grafts prior to surgery to prevent rejection. [4]

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Epidemiology

Frequency

United States

In 2016, 82,994 corneal transplantations were performed in the United States. [1] The incidence of graft rejection varies widely depending on the study design, type of transplantation, and risk factors for rejection. Reported incidences of penetrating keratoplasty graft rejection range from 2.3% to 68%. [5] At 5 years’ follow-up in the Cornea Donor Study, 23% of subjects had at least one rejection event, and 37% of the eyes with a rejection event had graft failure. [6]

Corneal graft rejection is the most common cause of graft failure in the late postoperative period. [2] The reported incidence of graft rejection is lower in endothelial keratoplasty. Descemet membrane endothelial keratoplasty (DMEK) has been reported to have a rejection rate as low as 0.7% at one year in one series, but other studies have reported higher rates. [7, 8]

Mortality/Morbidity

Corneal graft rejection is the most common cause of graft failure in the late postoperative period.

Race

No difference in corneal graft rejection between different races is known.

Sex

No sex predilection for corneal graft rejection is known.

Age

Host age may influence the risk of corneal graft rejection. Some investigators have concluded that hosts older than 60 years have a lower risk of corneal graft rejection, although this has not been confirmed. The effect of donor age on corneal graft survival has been debated. The Cornea Donor Study did not find an association between donor age and corneal graft survival among corneal transplants at moderate failure risk. [9] Infants have higher rates of graft rejection than adults.

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Prognosis

The sooner an episode of graft rejection is detected clinically and therapy is begun, the better the prognosis for graft survival. The rate of reversal of corneal endothelial graft rejection has been reported from 50-91%, depending on the clinical setting. In general, the prognosis is good if therapy is immediately instituted.

Depending on the degree of irreversible damage to the graft endothelium, even markedly edematous grafts may clear again. Once endothelial destruction has progressed to the point where the remaining endothelial function is inadequate to maintain deturgescence, the graft fails and becomes irreversibly edematous. Unfortunately, the endothelium has no or at best a very limited capacity for repair through mitosis.

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Patient Education

No symptoms are related universally to graft rejection.

Astute patients may complain of a decrease in visual acuity, redness, pain, irritation, and photophobia. Patients may also be asymptomatic.

Any patient with a corneal graft should be instructed to seek ophthalmologic care urgently if these symptoms persist for more than a few hours.

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