|Year : 2018 | Volume
| Issue : 2 | Page : 44-49
Donor factors influencing corneal tissue utilization in North India
Anuradha Raj1, Garima Mittal2, Harsh Bahadur1
1 Department of Ophthalmology, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Jolly Grant, Dehradun, Uttarakhand, India
2 Department of Microbiology, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Jolly Grant, Dehradun, Uttarakhand, India
|Date of Web Publication||7-Mar-2019|
Dr. Anuradha Raj
Department of Ophthalmology, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Jolly Grant, Dehradun, Uttarakhand
Purpose: The study aimed to determine the effect of various donor factors on utilization pattern of donor corneal tissue. Methods: This was a cross-sectional, retrospective study. Data of 509 donors with 1007 eyes details from eye bank (EB) were reviewed from December 2012 to June 2017. Donor data was analyzed including the age, sex of the donor, cause of death, source of tissue, death to enucleation time (DET), death to preservation time (DPT), type of tissue collected, grades of the tissue, serology reports and various utilization parameters. Results: Tissue utilization of EB was 356 out of 1007 which made 35.35% with cumulative utilization to the tune of 512 out of 1007 (50.84%). 82.50% tissues utilized for surgical use were from donor>65 years of age. Type and grading of tissue influenced the utilization of the tissues significantly (P = 0.00) each. Maximum keratoplasties 179 (50.28%), 202 (56.74%) were done with DET>3 hrs and DPT ≤4 respectively. DET, DPT and serology showed significant influence on the utility of the tissue (P = 0.00) each. Major cause of exclusion of the tissue for utilization was poor quality of the tissue which was C grade. Grading of tissue was significantly affected by DET, DPT and mode of tissue procured. Donor age >65 years showed higher surgical utility. Conclusion: Various donor factors like DET, DPT, tissue grade and type and serology results affects the utility of harvested corneal tissue. Potential modifiable donor factors needs to be addressed such as attention must be paid to the cause of death, contraindications and time factors related to donor.
Keywords: Grading of tissue, keratoplasty, serology
|How to cite this article:|
Raj A, Mittal G, Bahadur H. Donor factors influencing corneal tissue utilization in North India. Sudanese J Ophthalmol 2018;10:44-9
| Introduction|| |
Corneal blindness can be treated by corneal transplantation which is considered the most successful organ transplant. In India, despite the steady rise of collection of donor corneas, there is a huge gap between their demand and supply. Approximately 277,000 donor corneas are required to perform 100,000 corneal transplants annually to achieve utilization rate of 50% which is target of VISION 2020 program. Despite huge requirement, only 44,806 corneas are collected. Out of these, only 46% (20,632 eyes) are utilized for sight restoration as the other 54% do not meet the standards for transplantation. Hence, major chunk of procured cornea is unsuitable for corneal transplantation. Various donor-related factors can affect the graft clarity such as age of the donor, death-to-enucleation time (DET), death-to-preservation time (DPT), surface disorders, and endothelial status. In literature, ideal recommendations for eye banking are as follows: donor age <60 years, DET, and DPT <6 hr (h). These recommendations can be further modified according to tissue utilization.
Tissue utilization at an eye bank (EB) can reflect various causes of tissue exclusion which can be modified further to control corneal blindness in this developing country. To the best of our knowledge, only a few studies have been conducted so far which highlight the donor factors affecting utilization pattern of corneal tissue. Keeping this in view, this study was conducted to evaluate various donor factors affecting its utilization. Probing into these factors can help us to improve the utility of tissue procured at an EB despite limited tissue availability.
| Materials and Methods|| |
The study conducted was in accordance to the tenets set forth in the Declaration of Helsinki and was approved by the Institutional Research Ethical Committee. This was a cross-sectional, retrospective study in which we reviewed data of 509 donors with 1007 eyes details from EB from December 2012 to June 2017. Among these donors, 11 donors were single eyed.
EB received donor tissues from our hospital either mortuary or intensive care unit under hospital corneal retrieval program (HCRP), donor's homes, hospitals in city, adjacent areas through voluntary donors, and eye donation centers (EDCs). EB accepted all tissues with universal precautions, but in case of medical or serological contraindication for transplantation, relatives were counseled about unsuitability of the tissue for keratoplasty and the possibility of utilization of tissue for research or training purpose. Tissue was procured after informed consent otherwise enucleation was not performed. If on gross examination, the eyes look good with good corneal transparency, maintained anterior chamber, and few Descemet's folds, corneoscleral rim excision was performed. In case, if corneas were hazy with collapsed globe, with infiltrates, the whole-globe enucleation was done. Slit-lamp examination was done for epithelial defects or edema, exposure keratitis, arcus senilis, corneal scars, stromal edema or opacification, Descemet's membrane folds, endothelium quality, and condition of anterior chamber, iris, pupil, and lens status and examined for any iatrogenic perforation of anterior chamber. We evaluated donor corneas by standard grading system adapted from the Cornea Donor Study (NEI 2002–2013) Tissue Eligibility Criteria. Clinical grading as A, B+, B−, C, and D was assigned. In globes with grades of A, B+, and B−, corneoscleral rim excision were performed in a biological safety cabinet that provided a sterile area for the laminar flow cabinet which actually directed the airflow over the eye and onto the operator, thus presenting the potential for pathogens to aerosol onto the operator and preserved in McCarey-Kaufman (MK), and DPT in h was noted. In case, if the whole globe was of Grade C or D, they were considered unsuitable for keratoplasty purpose and were used for research or training purpose.
Serological examination of donor blood were performed for human immunodefi ciency virus (HIV), hepatitis B virus (hepatitis B surface antigen [HBsAg], hepatitis C virus (HCV), and syphilis (venereal disease research laboratory [VDRL].
Serological examination of donor blood were performed for human immunodeficiency virus (HIV), hepatitis B virus (hepatitis B surface antigen [HBsAg], hepatitis C virus (HCV), and syphilis (venereal disease research laboratory [VDRL]. If found reactive for any, respective donor corneal tissues were discarded and incinerated and personnel involved with that enucleation were intimated. Corneas with grades A+, A and B+ were utilized for keratoplasty (optical, therapeutic and lamellar). Some non-reactive good grade tissues had to be sent to other eye surgeons for the purpose of keratoplasty. If the nonreactive corneas of B− grade remained unutilized for 4 days were shifted to sterile glycerin solution in a sterile glass bottle having at 4°C, which were termed as long-term preserved (LTP). MK media of transferred tissue were sent for Gram's and KOH staining and culture, and if any contamination proved, those corneas were used for research purpose. Reasons for nonutilized or discarded tissues were noted. Various parameters of utilization of donor tissues were keratoplasty, research purpose, LTP, discarded or issued to other corneal surgeons.
Data analyzed included the age, sex of the donor, cause of death (cardiac arrest, cardiorespiratory arrest, malignancies, roadside accident, and septicemia), source of tissue (parent hospital, donor home, or EDCs), DET, DPT, type of tissue collected (whole globe or eyeball/corneoscleral button), grades of the tissue, serology reports reactive or nonreactive, and utilization parameters [Table 1].
Initially, data obtained were entered into an Excel spreadsheet and then transferred to the Statistical Package for the Social Sciences (SPSS) software (SPSS, version 22, SPSS Inc., Chicago, IL, USA) for analysis. Statistical data were expressed in terms of means ± standard deviations. The descriptive statistics was used to express data in terms of frequency and percentage. Pearson Chi-square test was used to find out the association between categorical variables. P < 0.05 was considered statistically significant.
| Results|| |
A total of 1007 corneas were received at our EB from December 2012 to June 2017. Among 509 donors, maximum donors 420 (82.50%) were >65 years of age. Male and female donors were 295 (58%) and 214 (42%), respectively. Maximum donors (354, 69.5%) died due to cardiac arrest. Maximum tissues (598, 59.4%) were procured by EDCs attached to this EB. Whole globe or eyeballs and corneoscleral buttons were collected as 469 (46.57%) and 538 (53.42%), respectively. Out of 1007, maximum corneas (433, 42.99%) were of Grade B+, and minimum corneas (58, 5.75%) were of Grade A. Of these 1007 corneas, 356 (35.35%) were transplanted. Out of 1007 corneas, 939 (93.24%) corneas were accepted and 68 (6.75%) were rejected or discarded which were eventually incinerated. Out of rejected tissues, 24 (2.38%) and 2 (0.19%) were discarded due to reactive serology to HBsAg and HCV, respectively. About 42 (4.17%) samples were not fit for serology [Table 1].
Donor cornea utilization for keratoplasty according to source of tissue
In this study, maximum utilization of the tissue was observed among which were collected by EDC, i.e., 183 out of 356 (51.40%) and minimum utilization was seen with the tissue collected by HCRP, i.e., 43 out of 356 (12.07%). Maximum tissues procured from HCRP were utilized for research purpose, i.e., 47 out of 92 (51.08%) as 26 (28.26%) of donors died of septicemia which was contraindicated for surgical utilization. Tissue utilization for keratoplasty at our eye center was 356 out of 1007 which made 35.35%. The tissue which was issued to other surgeons was utilized only for keratoplasty purpose which made cumulative utilization rate of our EB to the tune of 512 out of 1007 (50.84%) [Table 2].
Donor demographics and influence of the cause of death on donor cornea for transplantation
The majority of donors, i.e., 82.50 % were >65 years of age and 58% were men. The three main causes of death of the donors were cardiac arrest, respiratory failure, and roadside accidents with cardiac arrest in majority of cases, i.e., 286 (80.3%). Average DET was 4.25 h and DPT was 5.38 h. In majority 179 (50.3%) and 202 (56.7%) of cases, DET was >3 h and DPT was ≤4 h, respectively. Maximum (248, 69.7%) donor tissues utilized for optical purpose PK were of B + grade.
Various factors affecting tissue utilization
The grading of the tissue was signifi cantly affected by the DPT and DET (P = 0.00 and 0.00, respectively)). The type of tissue retrieved either in the form of whole globe or corneoscleral button in situ also affected the grading of the tissue significantly (P = 0.00). Source, type, and grading of the tissue received showed a significant impact on its utilization (P = 0.00, 0.00, and 0.00, respectively). Maximum keratoplasties, i.e., 179 (50.28%) and 202 (56.74%) were done with DET >3 h and DPT ≤4 h, respectively. DET, DPT, and serology results showed a significant influence on the donor tissue utility (P = 0.00, 0.00, and 0.00, respectively) [Table 2].
Exclusion of utilization
Major cause of excluding the tissue from transplantation use was poor tissue quality, i.e., C grade. All causes of exclusion are summarized in [Table 3].
| Discussion|| |
In the present study, 356 (35.35%) were utilized for surgeries at our center, but cumulative utilization was 512 (50.84%). A total of 598 (59.4%) tissues were received from other EDCs. Only 92 (9.1%) were from our own institute within a HCRP model. Maximum tissues (51.40%) collected by EDCs were utilized for keratoplasty purpose and minimum utilization (12.07%) was seen with the tissue collected by HCRP. Patel et al. reported cornea utilization rate was as high as 79% with 68% of tissues received from HCRP service on the contrary in the current study 51.08% of HCRP tissues were utilized for research purpose due to contraindicated causes of deaths. Oliva et al. found tissue utilization as high as 72% under HCRP which was higher as compared to the current study 12.07% which can be due to the fact that 29 (31.52%) donors died due to septicemia and malignancies which exclude the tissue for surgical utilization purpose.
Jadeja and Bhatt reported 33% utilization of cornea which was comparable with the present study.
Farge et al. and Moyes et al. reported that donor age >75 years was a major reason for exclusion., In this study, maximum tissues, i.e., 284 out of 356 (79.77%) belonged to the age group of >65 years which justify the fact that higher age limit cannot be criteria for exclusion of utility of the tissue. Armitage and Eastly reported a 45% of utility rate in donors of 80 years, and other previous studies have indicated that advanced donor age alone does not have an adverse effect on transplant survival outcome which justifies the results of the present study. Nonetheless, decreased endothelial cell density and function with advanced age are well established. Therefore, tissues from aged donors need a thorough endothelial assessment before approval for transplantation.
Gain et al. demonstrated that endothelial cell count during banking ensures that functional and cellular results of PK are not dramatically influenced by very old donor age. In the current study, we did not assess the corneal endothelium with specular microscope but used slit-lamp evaluation for corneal grading.
A nonreactive serological testing for HIV, HBsAg, VDRL, and HCV is mandatory before tissue transplantation. In this study, 68 (6.75%) of tissues could not be utilized and were incinerated as blood sample showed either reactive serology or insufficient or hemolyzed sera which was quite less as compared to 19% as reported by Jadeja and Bhatt.
In the current study, the seroprevalence of hepatitis B virus (HBV) and HCV viruses in eye donors was 2.4% and 0.2%, respectively, and no case showed reactive serology to HIV and VDRL. Mahalakshmi et al. reported the seroprevalence of HBV and HCV as 3.52% and 1.45%, respectively.
In another study done by EB Association of Australia and New Zealand, the seroprevalence of HBV and HCV was 0.49% and 0.38%, respectively, which was comparable to the current study. HBV is known to have been transmitted through corneal tissue. HBV DNA was detected in 6.6% of corneal epithelium and 14.8% of stromal tissue of seropositive eye donors. There is a significant risk of transmission of HBV to the enucleator, and special precautions are required to be taken to handle hepatitis virus-infected tissue.
HCV RNA has been detected in 34.5% in cornea, tears, and aqueous humor of seropositive patients; hence, it is essential to determine the infectious status of the eye donor with the virus. Since hepatitis C is life threatening, it is mandatory to screen potential cornea donors for HCV before transplantation. In the current study, the mean DPT was 6.1 ± 3.2 h, which is far better than a study done by Patel et al. who have shown this interval to be 15.2 ± 6.2 hrs. The lower the DPT, better the donor cornea quality. A study done by Van Meter et al. stated if the DPT is more than 6 h, it causes corneal epithelial sloughing and deterioration of the cornea.
Gogia et al. reported increased utilization rate of donor corneas over the years, primarily due to increase in usage of nonoptical grade corneas for therapeutic purposes. They reported meager 1.9% of donor tissue could be retrieved from eligible trauma-related deaths in eligible donors which is comparable to the present study with 2.8% which is due to lack of awareness and counseling.
Gyanchand concluded that tissues retrieved by HCRP were of transplantable grade and that would be the method to target the backlog of corneal blindness.
Limitations of the study
Grading of the tissues was done on slit lamp only. Specular microscope was not used for endothelial cell count and its morphological evaluation. Hence, grading of the tissue was more of subjective one and bias could not be ruled out. Death to refrigeration time was not taken into account for the analysis of utility of the donor tissue.
| Conclusion|| |
In summary, attention must be paid to the cause of death and ocular conditions as several general and ocular diseases constitute contraindication for donor cornea usage. Donor age >65 years contribute for higher utilization of donor cornea for keratoplasty purpose. The tissues from aged donors need a thorough endothelial assessment before approval for transplantation. HCRP shows lower utilization rate as they get influenced by illness of the donor which are contraindicated for utilization of the tissue. Various donor factors such as DET, DPT, and serology results affect the utility of harvested corneal tissue. Newer guidelines are warranted to reduce the contraindications for donor tissue utilization in safe manner.
We would like to thank Mr. Shubham Pandey, assistant professor and head biostatistics department, Mr. Ankit, lecturer department biostatistics for statistical analysis, and Mr. Surendra Singh Bhandari, office assistant for technical support and photographic documentation.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]