The Effect of ABO Blood Incompatibility on Corneal Transplant Failure in Conditions with Low-risk of Graft Rejection

doi:10.1016/j.ajo.2008.09.021

American Journal of Ophthalmology

Volume 147, Issue 3, March 2009, Pages 432-438.e3

https://doi.org/10.1016/j.ajo.2008.09.021 Get rights and content

Purpose

To determine whether corneal graft survival over a 5-year follow-up period was affected by ABO blood type compatibility in participants in the Cornea Donor Study undergoing corneal transplantation principally for Fuchs dystrophy or pseudophakic corneal edema, conditions at low-risk for graft rejection.

Design

Multi-center prospective, double-masked, clinical trial.

Methods

ABO blood group compatibility was determined for 1,002 donors and recipients. During a 5-year follow-up period, episodes of graft rejection were documented, and graft failures were classified as to whether or not they were attributable to immunologic rejection. Endothelial cell density was determined by a central reading center for a subset of subjects.

Results

ABO donor-recipient incompatibility was not associated with graft failure attributable to any cause including graft failure because of rejection, or with the occurrence of a rejection episode. The 5-year cumulative incidence of graft failure attributable to rejection was 32 (6%) for recipients with ABO recipient-donor compatibility and 12 (4%) for those with ABO incompatibility (hazard ratio, 0.65; 95% confidence interval, 0.33 to 1.25; P = .20). The 5-year incidence for a definite rejection episode, irrespective of whether graft failure ultimately occurred, was 64 (12%) for ABO compatible compared with 25 (8%) for ABO incompatible cases (P = .09). Among clear grafts at 5 years, percent loss of endothelial cells was similar in ABO compatible and incompatible cases.

Conclusions

In patients undergoing penetrating keratoplasty for Fuchs dystrophy or pseudophakic corneal edema, ABO matching is not indicated since ABO incompatibility does not increase the risk of transplant failure attributable to graft rejection.

Section snippets

Methods

Details of the CDS protocol have been reported previously.1, 5, 6 Briefly, subjects were between 40 and 80 years of age, with a diagnosed corneal condition associated with endothelial dysfunction that placed them at moderate risk of overall graft failure but low-risk of graft rejection, principally Fuchs dystrophy and pseudophakic corneal edema. Clinical investigators and subjects were masked to all characteristics of the donor corneal tissue, including age, endothelial cell density, and donor

Results

The characteristics of the cohort included in this study were similar to those of the full CDS population reported previously.5, 6 Sixty-four percent of the recipients were ABO compatible with their donor, 86% were Rh compatible, and 54% were both ABO and Rh compatible. ABO/Rh compatibility did not vary by any recipient or donor demographics including self-reported race/ethnicity (data not shown).

As seen in Table 1, graft failure attributable to rejection was not impacted by ABO compatibility.

Discussion

A search for immunologic factors that reduce graft survival has led researchers to examine the cornea for the presence of markers capable of inciting a rejection reaction. Among those examined have been human leukocyte antigen (HLA) Group I and Group II antigens, the ABO blood group antigens, and Lewis antigen. Studies of these antigens have shown some interesting, thought provoking, and controversial results.

The CCTS investigated, in a prospective study, the relationship between corneal

References (22)

The effect of donor age on corneal transplantation outcome: results of the cornea donor study
Ophthalmology
(2008)
Donor age and corneal endothelial cell loss five years after successful cornea transplantation: specular microscopy ancillary study results
Ophthalmology
(2008)
The Collaborative Corneal Transplantation Studies (CCTS): effectiveness of histocompatibility matching in high-risk corneal transplantation
Arch Ophthalmol
(1992)
W.H. Havener et al.
Cornea donor selection by blood type
Arch Ophthalmol
(1958)
Baseline donor characteristics in the Cornea Donor Study
Cornea
(2005)
Clinical profile and early surgical complications in the Cornea Donor Study
Cornea
(2006)
Design and methods of the Collaborative Corneal Transplantation Studies
Cornea
(1993)
An evaluation of image quality and accuracy of eye bank measurement of donor cornea endothelial cell density in the Specular Microscopy Ancillary Study
Ophthalmology
(2005)
B.A. Benetz et al.
Specular Microscopy Ancillary Study methods for donor endothelial cell density determination of Cornea Donor Study images
Curr Eye Res
(2006)
T.A. Gooley et al.
Estimation of failure probabilities in the presence of competing risks: new representations of old estimators
Stat Med
(1999)

M.G. Maguire et al.

Risk factors for corneal graft failure and rejection in the collaborative corneal transplantation studies

Ophthalmology

(1994)

Cited by (24)

Matching for Human Leukocyte Antigens (HLA) in corneal transplantation - To do or not to do
2015, Progress in Retinal and Eye Research
Citation Excerpt :
This type of rejection has been described in solid organ transplantation and is mediated by circulating antibodies, directed against ABO-blood group or HLA antigens or both; such antibodies may have developed as the result of a previous antigen exposure, such as a blood transfusion or pregnancy (Wood and Goto, 2012). With regard to corneal allografts, early studies found an influence of ABO incompatibility in high risk patients (Inoue and Tsuru, 1999; Maguire et al., 1994), but more recent studies did not confirm this (Dunn et al., 2009; Soma et al., 2004; Stulting et al., 2012). In contrast to the clear role which anti-HLA alloantibodies have in solid organ transplantation, their role is not entirely clear in corneal transplantation.
As many patients with severe corneal disease are not even considered as candidates for a human graft due to their high risk of rejection, it is essential to find ways to reduce the chance of rejection. One of the options is proper matching of the cornea donor and recipient for the Human Leukocyte Antigens (HLA), a subject of much debate. Currently, patients receiving their first corneal allograft are hardly ever matched for HLA and even patients undergoing a regraft usually do not receive an HLA-matched graft. While anterior and posterior lamellar grafts are not immune to rejection, they are usually performed in low risk, non-vascularized cases. These are the cases in which the immune privilege due to the avascular status and active immune inhibition is still intact. Once broken due to infection, sensitization or trauma, rejection will occur. There is enough data to show that when proper DNA-based typing techniques are being used, even low risk perforating corneal transplantations benefit from matching for HLA Class I, and high risk cases from HLA Class I and probably Class II matching. Combining HLA class I and class II matching, or using the HLAMatchmaker could further improve the effect of HLA matching. However, new techniques could be applied to reduce the chance of rejection. Options are the local or systemic use of biologics, or gene therapy, aiming at preventing or suppressing immune responses. The goal of all these approaches should be to prevent a first rejection, as secondary grafts are usually at higher risk of complications including rejections than first grafts.
Comparative cost-effectiveness analysis of descemet stripping automated endothelial keratoplasty versus penetrating keratoplasty in the United States
2013, American Journal of Ophthalmology
Citation Excerpt :
However, given that the rates are similar after the 2 different surgical procedures, it is unlikely that a slight increase in graft failure rate resulting from new-onset glaucoma would affect the cost-effectiveness analysis significantly. The current literature supports a lower allograft rejection rate for DSAEK than for PK (5.9% vs 10.6%, respectively).10,20,22–28 Based on our model, even with DSAEK rejection rates as high as 28%, DSAEK would remain a dominant procedure over PK.
To perform a comparative cost-effectiveness analysis of Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK) for corneal endothelial disease.
Retrospective cost-effectiveness analysis.
This cost-effectiveness analysis was performed from a third-party payer perspective with a 5-year time horizon. Probabilities of outcomes and complications of each of the procedures were calculated based on review of the published literature. A model was constructed to compare the costs and utilities associated with DSAEK and PK. Costs of donor tissue preparation, surgery, follow-up, postoperative complications, and procedures were considered. Utility values were based on quality-adjusted life years associated with visual acuity outcomes. Both costs and utilities were discounted at 3% per year. Sensitivity analyses were performed on key model inputs.
Base case analysis found DSAEK to be less costly compared with PK ($9362 vs $10 239), with greater utility (3.15 vs 2.47 quality-adjusted life years). Sensitivity analyses revealed that even at graft failure rates for DSAEK approaching the rates for PK, DSAEK would still reduce costs. Varying the dislocation rate in our model showed that even at dislocation rates approaching 50%, DSAEK remained less costly. Further, with DSAEK rejection rates as high as 28%, DSAEK would remain a dominant procedure over PK.
Comparative cost-effectiveness analysis of DSAEK versus PK indicates favorable cost and utility outcomes associated with DSAEK for treatment of corneal endothelial disease. Longer follow-up of DSAEK outcomes will provide more accurate information regarding long-term cost-effectiveness of the procedure.
Graft rejection after Descemet's stripping automated endothelial keratoplasty: Graft survival and endothelial cell loss
2012, Ophthalmology
To evaluate the effects of graft rejection episodes after Descemet's stripping automated endothelial keratoplasty surgery (DSAEK) on long-term endothelial cell density (ECD) decline and graft survival.
Retrospective, comparative analysis of an interventional case series.
We included 615 eyes of 415 Fuchs' dystrophy patients at a single institution with ≥6 months follow-up and without comorbidities known to influence postoperative ECD. All patients were enrolled as part of an ongoing, institutional review board-approved clinical protocol for a long-term, prospective study of endothelial keratoplasty in patients with endothelial dysfunction.
Preoperative specular microscopy of donor corneal tissue was performed. Postoperative specular microscopy measurements were recorded at 6 and 12 months, and yearly thereafter. The percentages of endothelial cell loss recorded at 1, 2, 3, and 4 years were compared with the Mann–Whitney U test.
Percentage ECD declines were calculated at each time point from the results of the preoperative and postoperative specular microscopy. Patients with graft rejection episodes and late endothelial failure were identified. Graft rejection was defined as findings of keratic precipitates with or without corneal edema, or anterior chamber cell and flare with or without corneal edema after the initial resolution of perioperative inflammation.
We identified 45 cases of graft rejection. The greatest number of rejections occurred between postoperative months 12 and 18. Eyes with a graft rejection episode had a higher median percentage decline in ECD at all time points compared with eyes without graft rejection episodes. This was statistically significant at 2 and 3 years postoperatively.
There is a trend toward a greater percentage of ECD loss with time in eyes experiencing graft rejection after DSAEK surgery.
Proprietary or commercial disclosure may be found after the references.
Rejection of corneal allografts
2011, Journal Francais d'Ophtalmologie
Le rejet d’allogreffe de cornée est la première cause d’échec des kératoplasties transfixiantes. C’est un processus immunologique complexe au cours duquel la reconnaissance d’allo-antigènes du greffon par le système immunitaire de l’hôte entraine une réponse immunitaire dirigée contre le greffon. Il peut toucher les différentes couches de la cornée, le rejet endothélial étant la forme la plus grave. Dans certains cas, le rejet mènera à l’échec définitif de la greffe. De nombreux facteurs de risque liés au donneur ou au receveur favorisent la survenue d’un épisode de rejet. La corticothérapie, par voie topique, locorégionale ou générale selon les cas, est le traitement préventif et curatif de référence du rejet. D’autres traitements immunosuppresseurs sont prometteurs mais demandent une évaluation plus précise. La détection précoce du rejet est essentielle, permettant d’instaurer rapidement un traitement agressif, et donc de diminuer le risque d’échec définitif de greffe, notamment par perte d’un nombre trop important de cellules endothéliales. La prévention du rejet repose aussi sur la compatibilité tissulaire entre donneur et receveur. La compatibilité ABO chez les patients à haut risque permet une diminution du risque de rejet. Une compatibilité HLA pourrait également avoir un intérêt dans certaines indications.
Corneal graft rejection is the major cause of penetrating keratoplasty failure. It is a complex immunological process that involves recognition of alloantigens from the corneal graft by the host's immune system, leading to an efferent immune response against the graft. Each layer of the cornea can undergo rejection, endothelial rejection being the most severe form. In some cases, rejection will lead to corneal graft failure. Many donor- and host-related risk factors contribute to corneal graft rejection. Corticosteroid therapy, topical or systemic, is the gold-standard in the preventive and curative treatment of rejection. Other immunosuppressive agents are promising but require further evaluation. Early detection of rejection is essential to establish an aggressive treatment and reduce the risk of graft failure. Prevention of rejection is also based on tissue matching between donor and recipient. In high-risk patients, ABO compatibility decreases the risk of rejection. HLA compatibility could positively influence corneal graft survival in some cases.
Management and prevention of corneal graft rejection
2023, Indian Journal of Ophthalmology
Long-term Outcomes after Lamellar Endothelial Keratoplasty Compared with Penetrating Keratoplasty for Corneal Endothelial Dysfunction: A Systematic Review
2023, Cornea

View all citing articles on Scopus

: Supplemental Material available at AJO.com.

View full text

Original articleThe Effect of ABO Blood Incompatibility on Corneal Transplant Failure in Conditions with Low-risk of Graft Rejection

Purpose

Design

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

The effect of donor age on corneal transplantation outcome: results of the cornea donor study

Ophthalmology

Donor age and corneal endothelial cell loss five years after successful cornea transplantation: specular microscopy ancillary study results

Ophthalmology

The Collaborative Corneal Transplantation Studies (CCTS): effectiveness of histocompatibility matching in high-risk corneal transplantation

Arch Ophthalmol

Cornea donor selection by blood type

Arch Ophthalmol

Baseline donor characteristics in the Cornea Donor Study

Cornea

Clinical profile and early surgical complications in the Cornea Donor Study

Cornea

Design and methods of the Collaborative Corneal Transplantation Studies

Cornea

An evaluation of image quality and accuracy of eye bank measurement of donor cornea endothelial cell density in the Specular Microscopy Ancillary Study

Ophthalmology

Specular Microscopy Ancillary Study methods for donor endothelial cell density determination of Cornea Donor Study images

Curr Eye Res

Estimation of failure probabilities in the presence of competing risks: new representations of old estimators

Stat Med

Risk factors for corneal graft failure and rejection in the collaborative corneal transplantation studies

Ophthalmology

Original article
The Effect of ABO Blood Incompatibility on Corneal Transplant Failure in Conditions with Low-risk of Graft Rejection