Objectives: The aim of this study was to evaluate the demographic features of corneal donors and available data of corneas in our eye bank during a 14-year period.

Materials and Methods: The demographic features of the corneal donors, the causes of death, the death-to-excision interval, serology results, the mean endothelial cell density, and the reasons for discarding the corneas were retrospectively evaluated.

Results: During the study period, 6524 corneas were retrieved from 3326 donors (76.1% male, 23.9% female). Mean donor age was 43.7 ± 16.0 years (range, 4-75 years; median 45.0 years). The most common cause of death was cardiovascular disease (n = 1467; 44.1%). The most common reason for discarding corneas was positive serology (n = 509; 78.6%). The mean endothelial cell density was 3030.1 ± 484.3 cells/mm². There was a weak negative statistically significant correlation between age and endothelial cell density (Pearson correlation coefficient r = -0.187, P < .001). Multiorgan donations made up 1.5% of the whole group (n = 50).

Conclusions: We believe that preoperative detailed evaluations of graft quality in addition to review of donor-related medical records and data from previous surgeries, after collecting them in a single system, will have a positive effect on postoperative corneal survival.

Key words : Corneal donation, Corneal donor demographics, Corneal donor procurement

Introduction

Corneal disorders, one of the significant reasons for blindness globally, have complex epidemiology and can be caused by infectious and inflammatory disorders of many types.¹ Surgical replacement of diseased corneas with healthy donor corneas can provide good visual results, with corneal transplant procedures having a long history.²

Eye banks are responsible for procuring, evaluating, storing, and distributing corneal tissue from suitable donors. The first relevant association in Turkey was the Turkish Eye Bank Association, which was established as part of Ankara University in 1957.³ Turkey currently has 48 eye banks.⁴ The eye bank of our own hospital was established in 2004 and has one of the highest numbers of procured corneas among the corneal banks of our country.

We reviewed data from a 14-year period of demographic features of corneal donors and features of procured corneas at our eye bank and evaluated whether any trends in these features over the years could be detected.

Materials and Methods

We retrospectively analyzed data of 3326 corneal donors registered at the University of Health Sciences, Kartal Dr. Lütfi Kırdar Training and Research Hospital’s Eye Bank (Istanbul, Turkey) between January 2006 and December 2019. The demographic features of the corneal donors, causes of death, the center procuring the cornea, the side of the procured cornea, the time between death and excision, donor serology, mean endothelial cell density (ECD), whether donors had volunteered to donate, the percentage of corneas used at our clinic and at an external center, and reasons for discarding corneas were recorded. All donor corneas were retrieved with the use of an in situ excision technique. The Konan Eye Bank KeratoAnalyzer EKA-04 (Konan Medical Corp, Hyogo, Japan) specular microscope was used for ECD measurements. The ECD value of donors with bilateral corneal excision was recorded as the mean ECD value of the 2 eyes, whereas unilateral measurement was entered for unilateral corneal excisions. A specular microscope was not available at our eye bank until 2010; therefore, it was not possible to measure ECD before that time. In addition, ECD was not measured in discarded corneas.

The Institutional Review Board and Ethics Committee of the Dr. Lutfi Kirdar Kartal Education and Research Hospital approved the initiation of the study (Institutional Review Board No. 2019/514/167/18). The study was conducted according to the tenets of the Declaration of Helsinki.

Statistical analyses
We used the Statistical Package for the Social Sciences Software (SPSS: IBM Company, version 17.0, IBM Corporation) for statistical analyses. Continuous variables are presented as means ± standard deviation. The Shapiro-Wilks test was used to determine whether group data had a normal distribution. The chi-square test and independent sample t test were used for evaluation. Between-group differences were determined with one-way analysis of variance (ANOVA) or Kruskal-Wallis using a post hoc test, Bonferroni, or Tamhane’s T2, depending on the distribution of the data. Pearson correlation analysis was used to determine the correlation between variables. Statistical significance level was accepted as P < .05.

Results

Donor demographics
During the study period, 6524 corneas were procured from 3326 donors. Corneas were procured from both eyes in 3198 donors (96.1%) and from 1 eye in 128 donors (3.9%). Demographic characteristics showed a disproportionate distribution between male (n = 2530; 76.1%) and female (n = 796; 23.9%) donors. Donor numbers and distribution in male and female donors for each year of the study are presented in Figure 1.

Average donor age was 43.7 ± 16.0 years (range, 4-75 years; median of 45.0 years). When mean age of donors was evaluated taking the year 2006 as reference, donor ages in 2010 and 2011 were found to be significantly lower (2006 vs 2010: P < .05; 2006 vs 2011: P < .05). No difference was observed in mean ages between the other years and 2006.

Mean age of donors by year is shown in Figure 2. Age of most donors was in the 51- to 60-year age group (n = 750; 22.5%) followed by the 41- to 50-year age group(n = 660; 19.8%). The distribution of donors by age range is presented in Figure 3.

Donor cause of death and discarded corneas
The most common causes of death of donors were cardiovascular disease (n = 1467; 44.1%), multiple trauma secondary to a traffic accident (n = 541; 16.3%), suicide (n = 366; 11.0%), and multiple trauma secondary to a fall from height (n = 236; 7.1%). Causes of death of donors are presented in Table 1.

We found that 649 of the corneas (9.9%) procured at our eye bank were discarded for various reasons. The most common cause for discarding corneas was found to be positive serology (n = 509, 78.5%). The rate of positive serology among the donors of the discarded corneas was 51.4% (n = 333) for hepatitis B virus, 10.3% (n = 67) for hepatitis C virus, 9.7% (n = 63) for HIV, 4.0% (n = 26) for syphilis, and 3.1% (n = 20) for coinfections. The discard rate due to seropositivity was 7.8% for all corneas in our study. The seroprevalence rates of hepatitis B virus, hepatitis C virus, HIV, syphilis, and coinfections among donors were 5.1%, 1.0%, 1.0%, 0.4%, and 0.3%, respectively. The most common ophthalmic reason for discard of corneas was corneal opacities (n = 27; 4.2%), whereas the most common external causes for discard of corneas were a change of color in the corneal storage solution (n = 25; 3.8%) and hemolyzed blood sample (n = 24; 3.7%). Reasons for discard of corneas are presented in Table 2.

Although the annual number of corneas procured at our eye bank varied significantly between 2006 and 2014, less variability was present between 2015 and 2019. No significant difference was observed in the number of discarded corneas by year (Figure 4).

Endothelial cell density of donor tissue and graft excision time
Endothelial cell density could be evaluated for 4028 corneal grafts (61.7%) in this study, and mean value was 3030.1 ± 484.3 cells/mm². No difference was found between male and female donors for mean ECD (P = .77, t test). A statistically significant weak correlation was present between age and ECD value (Pearson correlation coefficient, r = -0.187; P < .001). When donors were classified based on age groups, a statistically significant difference in the ECD was found between groups (F = 24.9, dF = 3; P < .001, one-way ANOVA). The difference was valid between all paired age group comparisons except for the 41- to 60-year and 61- to 80-year age groups. All paired comparisons between age groups and mean ECD values are presented in Table 3.

Mean duration between donor death and graft excision time (death-to-excision interval [DEI]) was 2.86 ± 3.24 hours (30 minutes to 16.3 hours). A statistically significant weak negative correlation was found between DEI and ECD, but the correlation coefficient was low (Pearson correlation coefficient of r = -0.074; P = .001).

Donor source, multiorgan donors, and the transplantation center
Distribution of donors of corneas procured at our eye bank within the study period was as follows: 2632 at our center (79.1%), 399 at Kosuyolu Heart and Research Hospital (KHRH) (12.0%), 205 at public hospitals (6.2%), 66 at research and training hospitals (2%), and 15 at private hospitals (0.5%).

A review of demographic data of donors from all centers showed no significant differences in terms of sex distribution (P > .05). There was dominance of male donors for all centers. Mean age of donors from the KHRH was significantly higher than in the other groups (P < .001, Kruskal-Wallis post hoc Tamhane’s T2). We found a significant difference between KHRH and the public hospitals in terms of duration between death and graft excision time (P < .05, Kruskal-Wallis post hoc Tamhane’s T2). Grafts from KHRH had been procured within a shorter time than in the public hospitals. There was no significant difference between the ECDs of grafts from different centers (P > .05, Kruskal-Wallis).

Among donors, 98.5% had provided only the cornea (n = 3276), whereas 1.5% (n = 50) were multiorgan donors. No statistically significant difference was found between mean age of multiorgan donors and other donors (P > .05, t test), but multiorgan donors included a higher percentage of female patients (P < .05, chi-square test). From 2006 to 2011, there were 6 multiorgan donors (0.4%); however, from 2012 to 2019, there were 41 such donors (2.4%) (P < .001, chi-square test), representing an increase in the share of multiorgan donors in recent years among the corneal donor group.

During the study period, 6524 corneas were received at our eye bank, with 5875 (90.1%) available after discarded corneas were excluded. Our own clinic used 93.4% of the donor corneas (n = 5492), whereas 6.6% (n = 383) were used in other corneal transplant centers affiliated with our eye bank.

Discussion

Corneal disorders make up 3.2% of the causes of visual loss worldwide, taking fifth place after cataract, refractive errors, glaucoma, and age-related macular degeneration.⁵ According to the data from the Turkish Ministry of Health, there are 48 eye banks and 590 corneal transplant centers in our country.^4,6 Between 2012 and 2019, the mean number of corneal transplants performed per year in our country was 3315.⁷ The number of people on the corneal transplant wait list across the country in 2019 was 1553.⁸ Thanks to the increase in the number of eye banks and corneal transplant centers, the number of people waiting for a corneal transplant in this country has decreased significantly in recent years.

The distribution of male versus female donors seems to be dominated by male donors in many eye bank studies, both nationally and internationally.^9-11 According to the 2016 data of the Eye Bank Association of America (EBAA), 60% of donors were male and 40% were female.¹² Similar to other studies, male dominance was seen among donors in our study (76.1% male vs 23.9% female donors). A study by the New Zealand National Eye Bank has reported that the causes of high mortality rates, such as cardiovascular disease and trauma, especially affect men in the young age groups and that this is reflected in the demographic data of the donors.¹¹ A similar distribution was also seen in our study, with a high rate of male donors and deaths due to heart diseases and with multiple trauma being more common in men.

No upper donor age limit has been specified in the European Eye Bank Association (EEBA) and EBAA’s latest report on medical standards for donors. The lower age limit has been reported to be less significant and should be determined depending on the surgical demand.^13,14 Although older donor corneas with lower endothelial count can be used in anterior lamellar keratoplasty, older donors are also preferred to facilitate graft preparation in Descemet membrane endothelial keratoplasty. In our clinic, we observed 2 peaks in the average donor age in 2013 and 2016. It is thought that this increase in average donor age might be related to the increase in the number of lamellar keratoplasties during these years. The mean age of corneal donors at our clinic was 43.7 ± 16.0 years (range, 4-75 years). The mean age of corneal donors at our eye bank was found to be lower than reported in the studies conducted at several eye banks.^9-11,15 According to the 2016 data from the EBAA, the age range of donors was mostly in the 61- to 70-year and 71- to 80-year age groups, whereas our donors were mostly in the 41- to 50-year and 51- to 60-year age groups.¹²

In EBAA’s review of causes of donor death between 2012 and 2016, cancer-related deaths took first place in all years.¹² Deaths due to cancer took sixth place among causes of death of donors at our clinic. This could be due to the difficulties experienced by our eye bank in reaching detailed death reports of donors. Insufficient data regarding the primary tumor of a potential corneal donor who died due to cancer may lead to hesitation in the use of the cornea. The low mean donor age in our study could be due to donors with cancer not being preferred and the high rate of young deaths due to multiple trauma in our group. Recommendations from the EEBA and EBAA with regard to donors with cancer have stated that corneas can be procured from donors other than those with a primary malignant ocular tumor, metastatic solid organ tumor, and hematological neoplasm (leukemia, lymphoma, myeloma).^13,14 We expect that more corneas will be procured at our eye bank in the coming years with the training to be given to our eye bank technicians and the studies to be conducted on having death reports include more details.

A review of eye bank data has shown that the most common cause for discarding corneas is serological results. The most common serology-related causes are hepatitis B virus, hepatitis C virus, HIV, and syphilis and more rarely coinfections.^16-18 The rate of cornea discard due to seropositivity was found to be 13.7% in a cornea bank study from Brazil.¹⁹ In eye bank studies from Turkey, discard rates of corneas due to seropositivity have ranged from 1.4% to 4.8%.^9,15,20 The seropositivity rate in donors was 10.5% in a study from an eye bank at another referral center in Western Turkey.²¹ In our study, the seropositivity rate among the donors related to discard rate due to seropositivity among all corneas was 7.8%. The discard rate due to seropositivity differs among regions in the eye bank studies from our country. According to the EBAA’s 2015 and 2016 data, the seropositivity rate among donors was approximately 7.4%.¹² Our study revealed similar rates.

The minimum ECD that enables the use of the donor cornea has been specified as 2000 cells/mm² in a 2000 report and 2300 cells/mm² in a 2006 report of the EBAA, whereas the New Zealand National Eye Bank has specified a value of 2500 cells/mm².^22-24 However, in recent years, the ECD restriction has been removed from the EBAA and EEBA criteria, and the responsibility has been left to the eye bank director.^13,14 The mean ECD in our study was 3030.1 ± 484.3 cells/mm2. A statistically significant negative correlation was found between donor age and ECD. Kwon and colleagues²⁵ have reported that the ECD of donors is affected by age, race, prior ocular surgery (cataract and refractive), and diabetes mellitus.

Endothelial cell density was found to be lower in older age, in some races, donors with a history of cataract or refractive surgery, and patients with diabetes mellitus compared with other groups.²⁵ In our study, we found that the ECD was especially high in donors from the 0- to 20-year age group. We were unable to evaluate the effects of previous systemic disorders and surgeries due to missing data of some donors. Although no correlation between DEI and ECD was found in other studies,^9,26 we found a statistically significant but weak negative correlation between DEI and ECD in our study. Ruusuvaara²⁷ found that ECD decreases as duration from death to enucleation increases. Although the EBAA and EEBA do not specify a definite period regarding DEI, their recommendations are to excise the graft and start corneal preservation procedures as soon as possible after death.

Corneas procured from voluntary organ donors constituted only 1.5% of the donors in our study. The percentage of female donors was higher among donors who donated their organs voluntarily. An increase in the share of multiorgan donors in the corneal grafts excised at our cornea bank in recent years was observed, but the ratio of voluntary donors was found to be lower than reported in other countries.^11,12 According to the Organ and Tissue Transplantation Services Regulation published in our country in 2000, corneas can be procured by medical staff unless there is a written declaration refusing corneal donation. Studies have been performed to raise awareness about organ donation in our country in recent years, but the number of donors is still inadequate. A study conducted on relatives of potential corneal donors has reported that effective results can be obtained in changing the corneal donation-related negative opinions of families when an active team provides information and the opportunity for discussion, even in those with low socio-economic status and no previous knowledge on the matter.²⁸ Although corneas can be procured without permission unless there is a declaration of refusal in our country, an increase in corneas to be procured from multiorgan donors will facilitate access to more detailed data about the donors.

Conclusions

In this study, we investigated the demographic features of corneal donors as recorded at our eye bank and 14 years of data belonging to corneas. As far as we know, our study is the most comprehensive eye bank study from tertiary referral centers in our country. We believe that detailed evaluations of graft quality preoperatively and evaluations of donor-related medical records and data from previous surgeries, once collected in a single system, will have a positive effect on corneal survival in the postoperative stage. In addition, a higher number of young donors and thus donor quality should be targeted by the Ministry of Health by ensuring adequate awareness of tissue and organ donation and ensuring communication and coordination between eye banks, forensic officials, and law enforcement.

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