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      Drugs & Diseases > Ophthalmology

      Corneal Graft Rejection

      Updated: Jan 23, 2023
      • 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 2021, approximately 80,000 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.
      View Media Gallery
      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.
      View Media Gallery
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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 lymphatics vessels or lymph nodes; therefore, the opportunity for presentation of foreign antigen to antigen-presenting cells and T cells also is 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. 

      Synthetic or bioengineered alternatives to human corneal tissue are being researched to reduce the risk for rejection. [4]

       

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      Epidemiology

      Frequency

      United States

      In 2021, 79,614 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] The incidence of graft rejection varies widely depending on the study design, type of transplantation, and risk factors for rejection. Overall graft survival rates also can vary among different indications for keratoplasty. Published data reveals a long-term graft survival rate of penetrating keratoplasty (PK) ranging from 52% to 98.8%. 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. [5] Another recent study of 405 eyes undergoing PK resulted in a graft survival rate of 73.5% and graft rejection rate of 14.1%, whereas another study demonstrated a rejection rate of 33.5%. [6, 7]

      The reported incidence of graft rejection is lower in partial thickness corneal transplantation. [8] The success rate for deep anterior lamellar keratoplasty (DALK) ranged from 77.0% to 99.3%. [9, 10] The incidence of graft rejection following DALK may range from 6% to 19.7%. [9, 7]

      Descemet stripping endothelial keratoplasty (DSEK) or Descemet stripping automated endothelial keratoplasty (DSAEK) usually is indicated for eyes with endothelial disease alongside other comorbidities (eg, glaucoma, iris defect, history of vitrectomy). [11] A retrospective study involving ultra-thin DSAEK (UT-DSAEK) demonstrated a graft survival rate of 99.1% and a rejection rate of 3.4% at one-year follow-up, and a survival rate of 94.2% and rejection rate of 6.9% at five-year follow-up. [12]

      Descemet membrane endothelial keratoplasty (DMEK) graft survival rates range from 92% to 100%, largely via reports from single-center data. [8] One recent retrospective study demonstrated a graft survival rate of 94.7% with a graft rejection rate of 1.7%. [6] Other large series data from single centers demonstrate a cumulative < 1% probability of graft rejection episode within 2 years following DMEK. [13, 14, 15] A meta-analysis of 10 retrospective studies showed a 60% lower risk of graft rejection following DMEK as compared with DSAEK. [16]

      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 for corneal graft rejection. Some investigators have concluded that hosts older than 60 years have a lower risk for 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 found no association between donor age and corneal graft survival among corneal transplants at moderate failure risk. [17] Corneal transplantation in the neonatal period (< 6 months) has a lower risk for rejection due to neonatal immune tolerance, with less active B cells. However, the immune system is fully developed and hyperactive by age 6 months, and thus the risk for graft rejection increases thereafter. [18]

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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 51-63.8%, depending on the clinical setting. [19, 20] 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 also may be asymptomatic. A useful pneumonic to use for patient education is “RSVP” (an acronym for Redness, Sensitivity to Light, Vision, and Pain), all representing symptoms that should be reported to the patient’s physician.

      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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