The Effect of Donor Age on Corneal Transplantation Outcome: Results of the Cornea Donor Study

doi:10.1016/j.ophtha.2008.01.003

Ophthalmology

Volume 115, Issue 4, April 2008, Pages 620-626.e6

https://doi.org/10.1016/j.ophtha.2008.01.003 Get rights and content

Objective

To determine whether graft survival over a 5-year follow-up period using corneal tissue from donors older than 65 is similar to graft survival using corneas from younger donors.

Design

Multicenter prospective, double-masked, controlled clinical trial.

Participants

One thousand ninety subjects undergoing corneal transplantation for a moderate-risk condition (principally Fuchs’ dystrophy or pseudophakic corneal edema); 11 subjects with ineligible diagnoses were not included.

Methods

Forty-three participating eye banks provided corneas from donors in the age range of 12 to 75 with endothelial cell densities of 2300 to 3300 cells/mm², using a random approach without respect to recipient factors. The 105 participating surgeons at 80 sites were masked to information about the donor cornea including donor age. Surgery and postoperative care were performed according to the surgeons’ usual routines. Subjects were observed for 5 years.

Main Outcome Measures

Graft failure, defined as a regraft or a cloudy cornea that was sufficiently opaque as to compromise vision for a minimum of 3 consecutive months.

Results

The 5-year cumulative probability of graft survival was 86% in both the <66.0 donor age group and the ≥66.0 donor age group (difference = 0%, upper limit of 1-sided 95% confidence interval = 4%). In a statistical model with donor age as a continuous variable, there was no significant relationship between donor age and outcome (P = 0.11). Three graft failures were due to primary donor failure, 8 to uncorrectable refractive error, 48 to graft rejection, 46 to endothelial decompensation (23 of which had a prior, resolved episode of probable or definite graft rejection), and 30 to other causes. Distributions of the causes of graft failure did not differ between donor age groups.

Conclusions

Five-year graft survivals for cornea transplants at moderate risk for failure are similar using corneas from donors ≥ 66.0 years and donors < 66.0. Surgeons and patients now have evidence that corneas comparable in quality to those used in this study from donors through age 75 are suitable for transplantation.

Section snippets

Materials and Methods

The protocol was approved by institutional review boards for all investigational sites. Each subject gave written informed consent to participate in the study. Study oversight was provided by an independent data and safety monitoring committee.

Eligible subjects were between 40 and 80 years old and had a corneal disease that placed them at moderate risk for graft failure (principally Fuchs’ dystrophy and pseudophakic corneal edema). An eye was not eligible if it was considered to be at high risk

Baseline Characteristics and Surgical Procedure

Between January 2000 and August 2002, 1090 eligible subjects were enrolled by 105 surgeons at 80 sites in the U.S. Mean age was 70±9 years; 697 (64%) were female, 1011 (93%) were Caucasian, 50 (5%) were African American, 13 (1%) were Hispanic, and 16 (1%) were of another race. Indications for corneal transplantation included Fuchs’ dystrophy in 676 (62%), pseudophakic/aphakic corneal edema in 369 (34%), and a variety of other causes in 45 (4%). Five hundred thirty-four (49%) eyes were

Discussion

In this study of 1090 moderate-risk cornea transplants, the overall 5-year success rate was 86% for grafts performed with corneas from donors 12 to 65 years old as well as for grafts performed with corneas from donors 66 to 75. The 95% CI on the observed difference was well within the study’s prespecified definition of noninferiority.

When donor age was analyzed as a continuous variable, there was not a significant donor age effect over the range of 12 to 75 years included in the study. However,

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Medical Standards

Cited by (142)

Quality assurance in corneal transplants: Donor cornea assessment and oversight
2024, Survey of Ophthalmology
The cornea is the most frequently transplanted human tissue, and corneal transplantation represents the most successful allogeneic transplant worldwide. In order to obtain good surgical outcome and visual rehabilitation and to ensure the safety of the recipient, accurate screening of donors and donor tissues is necessary throughout the process. This mitigates the risks of transmission to the recipient, including infectious diseases and environmental contaminants, and ensures high optical and functional quality of the tissues. The process can be divided into 3 stages: (1) donor evaluation and selection before tissue harvest performed by the retrieval team, (2) tissue analysis during the storage phase conducted by the eye bank technicians after the retrieval, and, (3) tissue quality checks undertaken by the surgeons in the operating room before transplantation. Although process improvements over the years have greatly enhanced safety, quality, and outcome of the corneal transplants, a lack of standardization between centers during certain phases of the process still remains, and may impact on the quality and number of transplanted corneas. Here we detail the donor screening process for the retrieval teams, eye bank operators. and ophthalmic surgeons and examine the limitations associated with each of these stages.
Characterisation of corneas following different time and storage methods for their use as a source of stem-like limbal epithelial cells
2021, Experimental Eye Research
The transplantation of expansions of limbal epithelial stem cells (LESC) remains one of the most efficient therapies for the treatment of limbal stem cell deficiency (LSCD) to date. However, the available donor corneas are scarce, and the corneas conserved for long time, under hypothermic conditions (after 7 days) or in culture (more than 28 days), are usually discarded due to poor viability of the endothelial cells. To establish an objective criterion for the utilisation or discarding of corneas as a source of LESC, we characterized, by immunohistochemistry analysis, donor corneas conserved in different conditions and for different periods of time. We also studied the potency of LESCs isolated from these corneas and maintained in culture up to 3 cell passages. We hoped that the study of markers of LESCs present in both the corneoscleral histological sections and the cell cultures would show the adequacy of the methods used for cell isolation and how fit the LESC enrichment of the obtained cell populations to be expanded was. Thus, the expressions of markers of the cells residing in the human limbal and corneal epithelium (cytokeratin CK15 and CK12, vimentin, Collagen VII, p63α, ABCG2, Ki67, Integrin β4, ZO1, and melan A) were analysed in sections of corneoscleral tissues conserved in hypothermic conditions for 2–9 days with post-mortem time (pmt) < 8 h or for 1 day with pmt > 16 h, and in sclerocorneal rims maintained in an organ culture medium for 29 days. Cell populations isolated from donor corneoscleral tissues were also assessed based on these markers to verify the adequacy of isolation methods and the potential of expanding LESCs from these tissues. Positivity for several putative stem cell markers such as CK15 and p63α was detected in all corneoscleral tissues, although a decrease was recorded in the ones conserved for longer times. The barrier function and the ability to adhere to the extracellular matrix were maintained in all the analysed tissues. In limbal epithelial cell cultures, a simultaneous decrease in the melan A melanocyte marker and the putative stem cell markers was detected, suggesting a close relationship between the melanocytes and the limbal stem cells of the niche. Holoclones stained with putative stem cell markers were obtained from long-term, hypothermic, stored sclerocorneal rims. The results showed that the remaining sclerocorneal rims after corneal transplantation, which were conserved under hypothermic conditions for up to 7 days and would have been discarded at a first glance, still maintained their potential as a source of LESC cultures.
Corneal endothelial dysfunction: Evolving understanding and treatment options
2021, Progress in Retinal and Eye Research
The cornea is exquisitely designed to protect the eye while transmitting and focusing incoming light. Precise control of corneal hydration by the endothelial cell layer that lines the inner surface of the cornea is required for optimal transparency, and endothelial dysfunction or damage can result in corneal edema and visual impairment. Advances in corneal transplantation now allow selective replacement of dysfunctional corneal endothelium, providing rapid visual rehabilitation. A series of technique improvements have minimized complications and various adaptations allow use even in eyes with complicated anatomy. While selective endothelial keratoplasty sets a very high standard for safety and efficacy, a shortage of donor corneas in many parts of the world restricts access, prompting a search for alternatives. Clinical trials are underway to evaluate the potential for self-recovery after removal of dysfunctional central endothelium in patients with healthy peripheral endothelium. Various approaches to using cultured human corneal endothelial cells are also in clinical trials; these aim to multiply cells from a single donor cornea for use in potentially hundreds of patients. Pre-clinical studies are underway with induced pluripotent stem cells, endothelial stem cell regeneration, gene therapy, anti-sense oligonucleotides, and various biologic/pharmacologic approaches designed to treat, prevent, or retard corneal endothelial dysfunction. The availability of more therapeutic options will hopefully expand access around the world while also allowing treatment to be more precisely tailored to each individual patient.
Animal models of high-risk corneal transplantation: A comprehensive review
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Over the past century, corneal transplantation has become the most commonly performed allogeneic solid tissue transplantation. Although more than 80% of the corneal transplantations have favorable outcomes, immune-mediated rejection continues to be the major cause of failure in well over 50% of graft recipients that have inflamed and vascularized host beds. Over the past two decades, the progress in our understanding of the immunological pathways that mediate graft rejection has aided in the development of novel therapeutic strategies. In order to successfully test the efficacy of these interventions, it is essential to model the immunological processes occurring as a consequence of corneal transplantation. Herein, we have comprehensively reviewed the established animal models used for replicating the immunopathological processes causing graft rejection in high-risk corneal transplantation settings. We have also discussed the practical and technical differences, as well as biological and immunological variations in different animal models.
Cost-Effectiveness of Antifungal Supplementation of Corneal Cold Storage Media
2020, Ophthalmology
To evaluate the cost-effectiveness of supplementing hypothermic cold storage media (CSM) with antifungal therapy.
Cost-effectiveness analysis (CEA).
Base case of a patient with Fuch’s endothelial dystrophy undergoing a first eye keratoplasty.
Cost-effective analysis of the base case with corneal tissue stored in CSM or CSM supplemented with antifungal therapy over a 16-year time horizon. Multiple clinical scenarios were considered, including endothelial keratoplasty (EK) and penetrating keratoplasty (PK); amphotericin B, voriconazole, caspofungin, and combination therapy; and third-party payer and societal perspectives. The incidences were derived from PubMed literature searches and average wholesale prices of medications; all costs were discounted 3% per annum and adjusted for inflation to 2019 US dollars.
Incremental cost-effectiveness ratios (ICERs).
In the reference case, a corneal endothelial graft stored in amphotericin B–supplemented CSM was the most cost-effective approach from a third-party payer and societal perspective. Probability sensitivity analysis (PSA) of the societal model for the EK was robust, with 93.5% being below an arbitrary willingness-to-pay threshold (WTP) of $20 000 per fungal infection averted. Voriconazole, caspofungin, and combination antifungals were less cost-effective than amphotericin B. The main factors influencing the CEA were the incidences of postkeratoplasty fungal infections, potential increases in graft failures, and antifungal costs. For grafts intended for PKs, antifungal supplementation was less cost-effective than for EKs.
Antifungal supplementation with amphotericin B for EK grafts was the most cost-effective approach of the studied antifungals; however, the CEA was sensitive to potential changes in graft failure rates, underlining the importance of long-term safety studies. For full-thickness corneal grafts, antifungal supplementation was less cost-effective.
Outcome of Descemet Membrane Endothelial Keratoplasty Using Corneas from Donors ≥80 Years of Age
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The purpose of this study was to investigate whether corneas from donors ≥80 years old are suitable for Descemet membrane endothelial keratoplasty (DMEK).
Retrospective, comparative, interventional case series.
Records of 1,765 consecutive DMEKs were reviewed and matched with corresponding donor tissue data. Older donors (≥80 years of age) were compared to younger donors (<80 years). Outcome measurements in DMEK recipients included best spectacle-corrected visual acuity (BSCVA), endothelial cell density (ECD), central corneal thickness (CCT) at 3 and 6 months and at 1, 2, and 3 years' follow-up and re-bubbling rates.
Of 1,748 DMEKs, 284 (16.2%) were performed with older donor lamellae (mean donor age, 83.96 ± 3.19 years; range, 80-94 years) and 1,464 (83.7%) with younger donor tissue (mean donor age, 65.27 ± 9.57 years; range, 17-79). BSCVA results were comparable for all postoperative time points. CCT results for younger donors were more favorable in the early postoperative course (P < 0.001 at 6 months; and P < 0.001 at 1 year), whereas mid-term results were comparable in both groups. ECD values were significantly higher in donors <80 years of age preoperatively and during the first 2 postoperative years (P ≤ 0.024). Overall re-bubbling rates were comparable in both groups.
Older donors, ≥80 to 94 years of age, seem to produce comparable mid-term functional results following DMEK surgery compared to younger donors. The use of corneas from donors aged ≥80 for DMEK surgery may therefore be a promising approach to counteract global donor shortage.

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: Manuscript no. 2007–1568.

: Supported by the National Eye Institute, Bethesda, Maryland (cooperative agreement nos. EY12728, EY12358). Additional support provided by Eye Bank Association of America, Washington, DC; Bausch & Lomb, Inc., Rochester, New York; Tissue Banks International, Baltimore, Maryland; Vision Share, Inc., Apex, North Carolina; San Diego Eye Bank, San Diego, California; Cornea Society, Fairfax, Virginia; Katena Products, Inc., Denville, New Jersey; ViroMed Laboratories, Inc., Minnetonka, Minnesota; Midwest Eye-Banks (Michigan Eye-Bank, Illinois Eye-Bank), Ann Arbor, Michigan; Konan Medical Corp., Torrance, California; Eye Bank for Sight Restoration, New York, New York; SightLife, Seattle, Washington; Sight Society of Northeastern New York (Lions Eye Bank of Albany), Albany, New York; and Lions Eye Bank of Oregon, Portland, Oregon.

: E-mail: [email protected].

^⁎: See “Appendix 2” (available at http://aaojournal.org) for a list of Group members.

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Original articleThe Effect of Donor Age on Corneal Transplantation Outcome: Results of the Cornea Donor Study

Objective

Design

Participants

Methods

Main Outcome Measures

Results

Conclusions

Section snippets

Materials and Methods

Baseline Characteristics and Surgical Procedure

Discussion

Ophthalmology

Ophthalmology

Ophthalmology

2006 Eye Banking Statistical Report

Eye Banking 1995: danger and opportunity

Cornea

Benefits of specular microscopy in evaluating eye donors aged 66 and older

Cornea

The impact on tissue utilization of screening donor corneas by specular microscopy at the University of Texas Southwestern Medical Center

Cornea

Tissue utilization at the Minnesota Lions’ Eye Bank

Cornea

Quality of corneal donor tissue in the greater-than-75-year age group

Cornea

Clinical profile and early surgical complications in the Cornea Donor Study

Cornea

Medical Standards

Original article
The Effect of Donor Age on Corneal Transplantation Outcome: Results of the Cornea Donor Study