Utilization rate and usage patterns of phakic and pseudophakic donor corneas recovered by the Singapore Eye Bank.

PURPOSE: To compare the utilization rate and usage patterns of pseudophakic and phakic donor corneas recovered by the Singapore Eye Bank. METHODS: Records of local donor corneas recovered by the Singapore Eye Bank from 2012 to 2017 were examined. Corneas that were deemed suitable for clinical use were stratified into phakic and pseudophakic groups. We examined the basic demographic pattern of both groups and the initial type of surgery/ies that the corneas were suitable for based on tissue parameters such as time from harvesting, stromal clarity, the clear central corneal area, the presence of Descemet's membrane tears or defects, and endothelial cell density and quality. We also identified the types of corneal grafts that the corneas were eventually used for; Penetrating Keratoplasty (PK), Anterior Lamellar Keratoplasty (ALK), Endothelial Keratoplasty (EK). Finally, the overall utilization rates for each group were determined. RESULTS: A total of 986 corneas deemed suitable for transplant were analyzed, 908 (92%) were phakic and 78 were pseudophakic (8%). The average age of pseudophakic donor corneas was (65 ± 8 yrs. old) and there was a slight male preponderance for both groups (55%). Age adjusted analysis of pseudophakic corneas showed the endothelial cell density (ECD) (mean: 2327 ± 47.1 cells/mm2) and clear area (mean: 7.0 ± 0.7 mm) were lesser than phakic corneas. The percentage of pseudophakic corneas that were of EK standard (ECD >2500 cells/mm2) were lower compared to phakic corneas (37% and 77% respectively, p < 0.001). There was significant correlation between previous cataract surgery and the endothelial cell count of the donor corneas (p < 0.001), and regression analysis also showed a strong association of ECD with cataract surgery in reference to non-cataract surgery (-478.8 (95% CI-576.9 to -380.7). The overall utilization rate for pseudophakic corneas was 58% compared to that of phakic corneas at 83%. The most common reason for pseudophakic corneas not to be utilized was due to the presence of Descemet's membrane (DM) tears or defects under the main or side port incision created during phacoemulsification (30%). Phakic corneas were used primarily for optical grafts 84% (mainly EK) while pseudophakic corneas were used mostly for therapeutic/tectonic grafts 47% (mainly ALK or patch grafts). CONCLUSION: Compared to phakic donor corneas, pseudophakic corneas generally have lower overall tissue quality leading to lower uptake by surgeons and lower utilization rates. Eye banks must continuously refine their donor acceptance criteria and engage surgeons to optimize utilization of each recovered tissue.

A cellular and proteomic approach to assess proteins extracted from cryopreserved human amnion in the cultivation of corneal stromal keratocytes for stromal cell therapy.

BACKGROUND: Human corneal stromal keratocytes propagated in culture media supplemented with human amnion extract (AME) can correct early corneal haze in an animal model. Clinical application of cultivated keratocytes is limited by infectious disease screening before amnion products can be used in humans. It remains unclear if AME from cryopreserved versus fresh human amnion can support human keratocyte propagation, and which components of the extract promote keratocyte growth. METHODS: Three placentas were collected for the preparation of fresh and cryopreserved amnion tissues followed by homogenization and protein extraction. AME protein profiles were studied using isobaric tagging for relative and absolute quantitation (iTRAQ) proteomics. Enriched gene ontology (GO) terms and functional classes were identified. Primary human keratocytes from 4 donor corneas were cultured in media supplemented with fresh AME (F-AME) or cryopreserved AME (C-AME). Cell viability, proliferation and keratocyte marker expression were examined by confocal immunofluorescence and flow cytometry. RESULTS: AME proteomics revealed 1385 proteins with similar expression levels (between 0.5- and 2-fold) between F- and C-AME, while 286 proteins were reduced (less than 0.5-fold) in C-AME. Enriched GO term and biological pathway analysis showed that those proteins with comparable expression between F-AME and C-AME were involved in cell metabolism, epithelial-mesenchymal transition, focal adhesion, cell-extracellular matrix interaction, cell stress regulation and complement cascades. Human corneal stromal keratocytes cultured with F-AME or C-AME showed similar morphology and viability, while cell proliferation was mildly suppressed with C-AME (P > 0.05). Expression of aldehyde dehydrogenase 3A1 (ALDH3A1) and CD34 was similar in both cultures. CONCLUSION: AME from cryopreserved amnion had limited influence on keratocyte culture. It is feasible to use protein extract from cryopreserved amnion to propagate human keratocytes for potential translational applications.

Cost Minimization Analysis of Precut Cornea Grafts in Descemet Stripping Automated Endothelial Keratoplasty.

Descemet stripping automated endothelial keratoplasty (DSAEK) is the most common corneal transplant procedure. A key step in the procedure is preparing the donor cornea for transplantation. This can be accomplished via 1 of 3 alternatives: surgeon cuts the cornea on the day of surgery, the cornea is precut ahead of time in an offsite facility by a trained technician, or a precut cornea is purchased from an eye bank. Currently, there is little evidence on the costs and effectiveness of these 3 strategies to allow healthcare providers decide upon the preferred method to prepare grafts.The aim of this study was to compare the costs and relative effectiveness of each strategy.The Singapore National Eye Centre and Singapore Eye Bank performed both precut cornea and surgeon-cut cornea transplant services between 2009 and 2013.This study included 110 subjects who received precut cornea and 140 who received surgeon-cut cornea. Clinical outcomes and surgical duration were compared across the strategies using the propensity score matching. The cost of each strategy was estimated using the microcosting and consisted of facility costs and procedural costs including surgical duration. One-way sensitivity analysis and threshold analysis were performed.The cost for DSAEK was highest for the surgeon-cut approach ($13,965 per procedure), followed by purchasing precut corneas ($12,659) and then setting up precutting ($12,421). The higher procedural cost of the surgeon-cut approach was largely due to the longer duration of the procedure (surgeon-cut = 72.54 minutes, precut = 59.45 minutes, P < 0.001) and the higher surgeon fees. There was no evidence of differences in clinical outcomes between grafts that were precut or surgeon-cut. Threshold analysis demonstrated that if the number of cases was below 31 a year, the strategy that yielded the lowest cost was purchasing precut cornea from eye bank. If there were more than 290 cases annually, the cheapest option would be to setup precutting facility.Our findings suggest that it is more efficient for centers that are performing a large number of cornea transplants (more than 290 cases) to set up their own facility to conduct precutting.

A cost-minimization analysis of tissue-engineered constructs for corneal endothelial transplantation.

Corneal endothelial transplantation or endothelial keratoplasty has become the preferred choice of transplantation for patients with corneal blindness due to endothelial dysfunction. Currently, there is a worldwide shortage of transplantable tissue, and demand is expected to increase further with aging populations. Tissue-engineered alternatives are being developed, and are likely to be available soon. However, the cost of these constructs may impair their widespread use. A cost-minimization analysis comparing tissue-engineered constructs to donor tissue procured from eye banks for endothelial keratoplasty was performed. Both initial investment costs and recurring costs were considered in the analysis to arrive at a final tissue cost per transplant. The clinical outcomes of endothelial keratoplasty with tissue-engineered constructs and with donor tissue procured from eye banks were assumed to be equivalent. One-way and probabilistic sensitivity analyses were performed to simulate various possible scenarios, and to determine the robustness of the results. A tissue engineering strategy was cheaper in both investment cost and recurring cost. Tissue-engineered constructs for endothelial keratoplasty could be produced at a cost of US$880 per transplant. In contrast, utilizing donor tissue procured from eye banks for endothelial keratoplasty required US$3,710 per transplant. Sensitivity analyses performed further support the results of this cost-minimization analysis across a wide range of possible scenarios. The use of tissue-engineered constructs for endothelial keratoplasty could potentially increase the supply of transplantable tissue and bring the costs of corneal endothelial transplantation down, making this intervention accessible to a larger group of patients. Tissue-engineering strategies for corneal epithelial constructs or other tissue types, such as pancreatic islet cells, should also be subject to similar pharmacoeconomic analyses.

Donor and surgical risk factors for primary graft failure following Descemet's stripping automated endothelial keratoplasty in Asian eyes.

BACKGROUND: Descemet's stripping automated endothelial keratoplasty (DSAEK) has been shown to have superior refractive and visual results compared with penetrating keratoplasty, but higher rates of primary graft failure (PGF). This paper presents donor and surgical risk factors for PGF in DSAEK cases in Asian eyes. DESIGN: Retrospective case-control study. PARTICIPANTS: All consecutive patients who underwent DSAEK at a tertiary referral teaching hospital from March 2006-December 2008. METHODS: DONOR DETAILS ANALYZED WERE: age of donor, cause of donor death, death to harvesting time, donor storage time, distribution distance of tissue, preoperative endothelial cell count. Surgical factors analyzed were: donor diameter, donor thickness, and method of donor insertion. These risk factors in cases of PGF were compared with patients with successful DSAEK as the control group. MAIN OUTCOME MEASURE: PGF. RESULTS: A total of 124 DSAEK procedures were performed. Six DSAEK procedures (five eyes of five patients; one eye with two failures) resulted in PGF (4.8%). Significant risk factors were found for PGF to include graft insertion using a folding technique (odds ratio [OR], 34.03; 95% confidence interval [CI], 3.75-314.32; P = 0.0017) and a small donor diameter (OR, 39.94; 95% CI, 2.18-732.17; P = 0.013). CONCLUSION: The results of this study suggest that in Asian eyes with shallow anterior chambers, surgical trauma relating to the technique of donor insertion, and the use of a small donor are major risk factors for PGF following DSAEK.

Risk factors for contact lens-related fusarium keratitis: a case-control study in Singapore.

OBJECTIVE: To evaluate the specific contact lens-related or other factors that may contribute to the outbreak of Fusarium keratitis. METHODS: A case-control study was conducted of Fusarium keratitis in contact lens users in Singapore from March 1, 2005, to May 31, 2006, and included 61 patients with Fusarium keratitis and 188 population-based and 179 hospital-based control subjects. Interviewers asked about contact lens solution use and other risk factors. RESULTS: Patients with Fusarium keratitis were more likely to use ReNu contact lens solutions (Bausch & Lomb, Rochester, NY) 58 [95.1%] of 61 cases) than were either population-based (62 [34.3%] of 181) or hospital-based (50 [30.1%] of 166) control subjects. After controlling for age, sex, contact lens hygiene, and other factors, the use of ReNu with MoistureLoc significantly increased the risk of Fusarium keratitis (odds ratio, 99.3; 95% confidence interval, 18.4-535.4; P<.001), and the risk was 5 times higher compared with the risk with use of ReNu MultiPlus, a multipurpose solution (odds ratio, 21.5; 95% confidence interval, 4.0-115.5; P<.001). CONCLUSIONS: The use of ReNu contact lens solutions significantly increased the risk of contact lens-related Fusarium keratitis in Singapore. Our data support the recall of ReNu MultiPlus from the Singapore market and the need for further investigations into the role of ReNu MultiPlus in the development of Fusarium keratitis in other populations.