Ocular tissue distribution in the State of São Paulo: analysis on corneal discarding reasons *

Objective to identify the reasons for refusal of corneas. Method this was a cross-sectional, retrospective, descriptive and correlational study composed of 5,560 optical corneas. The information was taken from the notification, organ procurement and distribution centers database as well as donor records. Descriptive statistics were used for the analysis of categorical variables and specific tests with a significance level of 5% for assessing the associations between variables. This study met the ethical aspects of scientific research. Results 60% of the donors were male and 40% died by circulatory problems. The main reason for refusal as informed by transplant teams is the donor’s age and the endothelial cell count. For each year added to the donor’s age, there is a 1% decrease in the chance that this cornea will be used for transplantation, and the increase of 100 cells per mm2 increases the chances that this cornea will be used by 9%. Conclusion the main cause of refusal in the acceptance of corneal tissue is related to the age and the endothelial cell count.


Introduction
Corneal diseases are the third cause of blindness worldwide, after the cataract and the glaucoma. Currently, more than 10 million people suffer from bilateral corneal diseases. Over 53% of the world's population does not have access to corneal transplantation (1) .
Brazil had over 5.379 patients in the waiting list for a cornea transplantation in 2013, and 13.744 procedures were carried out that year (2) . At the end of 2017 the number of patients in the waiting list was 9.266 and the number of transplants carried out was 15.242 (3) . There is still a great number of underreported cornea donors considering the number of deaths in health institutions (1,227,039 deaths/2014) (2) and the possibility of these patients become effective donors.
There are States and municipalities in Brazil with a greater number of donors and, therefore, with more cornea offers to transplantation centers.

The number of corneal transplants carried out in
Brazil is lower than expected, considering the number of corneas retrieval. There is no statistical data that may reveal the exact number of corneas reported, considering the overall number of deaths, not even a record of discarded corneas.   study and the sample was composed of 5,560 corneas.
Data collection script included [1] donordemographic variables (city where death occurred, domicile, age, sex, etc.), [2] retrieval andpreservation of tissue (time between death and enucleation, time between death andpreservation, and information on body cooling), [3] cornea quality (epithelium, halo, edema, Descemet's Membrane folds, guttata, density and cell count), [4] distribution and [5] refusal formed by transplantation teams. All the optic corneas available in the State of São Paulo for transplantation were analyzed. In order to collect data, a team of professionals with technical knowledge was trained to extract SIGSET information

Results
Out of the 5,560 corneas evaluated, 60.2% came from male donors, with an average age of 53 years (median 56, minimum two, maximum 80, first quartile 42 and third quartile 66) and 40.3% of corneas came from donors whose cause of death was related to circulatory system diseases. Out of these, 80% were accepted and transplanted.
The main causes of refusal informed by transplantation teams at the time of the offer of the corneas were the quality of the cornea (35.2%), team in another procedure (28%), long distance to remove the cornea (19.2%), too long preservation time (6.1%), other causes (11.5%). On average, each cornea had 9.3 refusals before being used or disposed of.
There was an association between transplantation and age (p<0.001) and cause of death (p<0.001), since corneas from donors between 15 and 49 years presented higher transplant (acceptance) percentages than corneas whose donors were older than 50 years.
Corneas from donors who have died by external causes  Corneas that had a score two concerning Descemet's membrane folds have 17% more refusals (p=0.004).

For each 100-cells increase per mm 2 there is a 15%
reduction in the average number of refusals (p<0.001).

Discussion
The results reveal similarity regarding gender and cause of death of the organ and tissue donors. In 2014, data from the Ministry of Health showed that 56.5% of deaths were related to male. The main cause of death was also related to circulatory system diseases, with 27.7%, followed by the neoplastic diseases, with 16.4% (5)(6) . Other studies have found a higher number of male donors (7)(8)(9)(10)(11)(12)(13)(14) . Out of 2,854 effective donors in 2015 in Brazil, 59% were male (15) .
In this research, we observed that 63% of donors were over 50 years, considering that there is a 80-yearold limit to donations, as determined by the Portaria 2.600, of October 21st 2009 (16) . The literature shows that when there are more cornea donors than receptors, transplantation teams tend to choose corneas from younger donors (17) .
The main causes of refusal or dispose of ocular tissue found in this study were related to cornea quality (35,2%), unavailability of the team for being in another procedure (28%) and long distance to remove the cornea (19.2%). According to data from the National Health Surveillance Agency, 12% of the total collected eyeballs in Brazil were disposed of due to poor quality in 2014 (18) .

A research with Canadian corneal transplant doctors
found that donor quality is one of the contributing factors to increase the waiting time for corneal transplants (19) . and whose cause of death was associated with external causes had a higher percentage of transplant (p<0.001).
It is worth mentioning that these donors had a higher percentage of endothelial cell count when compared with other donors.
Another study corroborates our findings showing that donors whose cause of death was related to external causes had a higher average of endothelial cell count (20) . Other studies have shown statistically significant association between increased donor age and decreased endothelial cell density (7)(8)10,(21)(22) .
A study carried out in an eye bank showed that corneas from donors who were aged between 20 and 29 years had higher percentages of classification as optics (14) . Endothelial density reduction caused by the advancement of donor age reduces the likelihood of these older donor corneas to be used for transplants (8) .
However, many corneas of donors over 80 years old have quality to be transplanted.
Donors whose cause of death was trauma have better cornea quality, when compared with corneas from donors with other causes of death (23) . When there are more cornea donors thanreceptors, transplant doctors tend to choose corneas from donors whose death was acute trauma-related (17) .
Cornea donors whose cause of death was trauma were 50% less likely to show graft failure when compared with corneas from donor who died from other causes (24) .
Some diseases such as Diabetes Mellitus and history of cataract surgery, affect the quality of the cellular density of the endothelium (22) . We did not find other studies that deal with distribution and allocation of corneal tissue.

Conclusion
The main reasons for refusal or disposal informed by transplantation teams are related to the quality of corneas offered by the Transplant Center. It was observed that corneas from donors whose body was in cold storage were less rejected. Corneas from younger donors whose cause of death was related to external causes had a higher percentage of use for transplants.
Similarly, for each increase of 100 cells per mm 2 on donor corneas, there is an increase of 9% of this cornea being used for transplantation and a reduction of 1% on average of refusals. For each one-year increase in donor age, there is a reduction of 1% in the chance of the cornea being accepted for transplant.
As assessed, quality is one of the major factors associated with refusal, and the quality is greater in younger donor corneas. One way of improving tissue quality and thus lowering the refusal would be to limit through to gain access to the tissue, to create ways that allow this cornea to reach the transplantation team.
The most important limitation of this study is the fact that transplantation clinical follow-up data was not included, correlating the success or failure of the transplant with the quality of the corneas offered. Because this is an observational and retrospective study, it is not possible to establish a cause and effect relationship.