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.

[1]  S. Tseng,et al.  Nuclear p120 catenin unlocks mitotic block of contact-inhibited human corneal endothelial monolayers without disrupting adherent junctions , 2012, Journal of Cell Science.

[2]  S. Bonner-Weir,et al.  Stem cell therapy for type 1 diabetes mellitus , 2010, Nature Reviews Endocrinology.

[3]  D. Tan,et al.  Endothelial keratoplasty: a revolution in evolution. , 2012, Survey of ophthalmology.

[4]  J. Mehta,et al.  Descemet stripping automated endothelial keratoplasty with a graft insertion device: surgical technique and early clinical results. , 2011, American journal of ophthalmology.

[5]  H. Deng,et al.  Evaluation of islets derived from human fetal pancreatic progenitor cells in diabetes treatment , 2013, Stem Cell Research & Therapy.

[6]  J. Mehta,et al.  Corneal transplantation: changing techniques. , 2011, Transplantation.

[7]  Kevin W. Ross,et al.  Impact of Surgeon Acceptance Parameters on Cost and Availability of Corneal Donor Tissue for Transplantation , 2013, Cornea.

[8]  K. Bartz-Schmidt,et al.  Decellularized Bovine Corneal Posterior Lamellae as Carrier Matrix for Cultivated Human Corneal Endothelial Cells , 2012, Current eye research.

[9]  M. Sefton,et al.  Tissue engineering. , 1998, Journal of cutaneous medicine and surgery.

[10]  Noriko Koizumi,et al.  Cultivated corneal endothelial cell sheet transplantation in a primate model. , 2007, Investigative ophthalmology & visual science.

[11]  Baoqin Han,et al.  Fabrication and characters of a corneal endothelial cells scaffold based on chitosan , 2011, Journal of materials science. Materials in medicine.

[12]  N. Koizumi,et al.  Corneal Endothelial Cell Fate Is Maintained by LGR5 Through the Regulation of Hedgehog and Wnt Pathway , 2013, Stem cells.

[13]  G. Melles,et al.  Descemet membrane endothelial keratoplasty (DMEK). , 2006, Cornea.

[14]  F. Price,et al.  Descemet's stripping with endothelial keratoplasty in 50 eyes: a refractive neutral corneal transplant. , 2005, Journal of refractive surgery.

[15]  H E Kaufman,et al.  Corneal transplantation. , 1977, Annual review of medicine.

[16]  D. Coster,et al.  Is viral nucleic acid testing of eye donors cost‐effective? , 2009, The Medical journal of Australia.

[17]  N. Joyce,et al.  Proliferative response of corneal endothelial cells from young and older donors. , 2004, Investigative ophthalmology & visual science.

[18]  P. Leung,et al.  Current progress in stem cell research and its potential for islet cell transplantation. , 2012, Current molecular medicine.

[19]  J. Mehta,et al.  Identification of cell surface markers glypican-4 and CD200 that differentiate human corneal endothelium from stromal fibroblasts. , 2013, Investigative ophthalmology & visual science.

[20]  M. Goldacre,et al.  Trends in corneal graft surgery in the UK , 2010, British Journal of Ophthalmology.

[21]  Alan Colman,et al.  Human corneal endothelial cell expansion for corneal endothelium transplantation: an overview. , 2011, Transplantation.

[22]  F. Prósper,et al.  Strategies of human corneal endothelial tissue regeneration. , 2013, Regenerative medicine.

[23]  J. Mehta,et al.  Cultivation of Human Corneal Endothelial Cells Isolated from Paired Donor Corneas , 2011, PloS one.

[24]  S. Yamagami,et al.  Increased proliferation and replicative lifespan of isolated human corneal endothelial cells with L-ascorbic acid 2-phosphate. , 2011, Investigative ophthalmology & visual science.

[25]  M. Mannis,et al.  Eye Banking and the Changing Trends in Contemporary Corneal Surgery , 2010, International ophthalmology clinics.

[26]  Jodhbir S. Mehta,et al.  Plastic Compressed Collagen as a Novel Carrier for Expanded Human Corneal Endothelial Cells for Transplantation , 2012, PloS one.

[27]  C. Cursiefen,et al.  Split cornea transplantation: relationship between storage time of split donor tissue and outcome. , 2013, Ophthalmology.

[28]  Marcus Ang,et al.  Cost-effectiveness of Descemet's stripping endothelial keratoplasty versus penetrating keratoplasty. , 2013, Ophthalmology.

[29]  E. Finkelstein,et al.  Incremental cost-utility analysis of deep anterior lamellar keratoplasty compared with penetrating keratoplasty for the treatment of keratoconus. , 2011, American journal of ophthalmology.

[30]  R. Tandon,et al.  One donor cornea for 3 recipients: a new concept for corneal transplantation surgery. , 2007, Archives of ophthalmology.

[31]  Bo Chen,et al.  Stem cell-based strategies for the treatment of type 1 diabetes mellitus , 2011, Expert opinion on biological therapy.

[32]  A. Utria Eye Bank Association of America , 2014 .

[33]  G. Cole Managing the future of cornea supply and demand: the costs affecting eye banking. , 1994, Cornea.

[34]  Noriko Koizumi,et al.  Cultivated Corneal Endothelial Transplantation in a Primate: Possible Future Clinical Application in Corneal Endothelial Regenerative Medicine , 2008, Cornea.

[35]  F. Kruse,et al.  Split cornea transplantation for 2 recipients - review of the first 100 consecutive patients. , 2011, American journal of ophthalmology.

[36]  F. Kruse,et al.  Split cornea transplantation for 2 recipients: a new strategy to reduce corneal tissue cost and shortage. , 2011, Ophthalmology.

[37]  G. Leibowitz,et al.  Islet transplantation in type 1 diabetes: hype, hope and reality – a clinician's perspective , 2014, Diabetes/metabolism research and reviews.

[38]  J. Mehta,et al.  Propagation of Human Corneal Endothelial Cells: A Novel Dual Media Approach , 2015, Cell transplantation.

[39]  J. Mehta,et al.  Paradigm shifts in corneal transplantation. , 2009, Annals of the Academy of Medicine, Singapore.

[40]  J. Mehta,et al.  Optimization of human corneal endothelial cell culture: density dependency of successful cultures in vitro , 2013, BMC Research Notes.

[41]  J. Sugar,et al.  Clinical Profile and Early Surgical Complications in the Cornea Donor Study , 2006, Cornea.

[42]  Roni M. Shtein,et al.  Corneal Donor Tissue Preparation for Endothelial Keratoplasty , 2012, Journal of visualized experiments : JoVE.

[43]  J. Vacanti,et al.  Tissue engineering : Frontiers in biotechnology , 1993 .

[44]  T. Young,et al.  Novel chitosan-polycaprolactone blends as potential scaffold and carrier for corneal endothelial transplantation , 2012, Molecular vision.

[45]  R. H. Wijdh,et al.  A Technique to Excise the Descemet Membrane From a Recipient Cornea (Descemetorhexis) , 2004, Cornea.

[46]  N. Sharma,et al.  Optimal Use of Donor Corneal Tissue: One Cornea for Two Recipients , 2011, Cornea.

[47]  J. Boyer,et al.  Guidelines for performing a pharmacoeconomic analysis. , 1992, American journal of hospital pharmacy.

[48]  H. Menegay,et al.  Descemet's stripping automated endothelial keratoplasty: three-year graft and endothelial cell survival compared with penetrating keratoplasty. , 2013, Ophthalmology.

[49]  C. Ricordi,et al.  Stem cell-derived islet cells for transplantation , 2011, Current opinion in organ transplantation.

[50]  A. Shapiro,et al.  State of the Art of Clinical Islet Transplantation and Novel Protocols of Immunosuppression , 2011, Current diabetes reports.

[51]  Kohji Nishida,et al.  A novel gelatin hydrogel carrier sheet for corneal endothelial transplantation. , 2011, Tissue engineering. Part A.

[52]  N. Koizumi,et al.  ROCK inhibitor converts corneal endothelial cells into a phenotype capable of regenerating in vivo endothelial tissue. , 2012, The American journal of pathology.

[53]  U. Schlötzer-Schrehardt,et al.  Reproducibility of graft preparations in Descemet's membrane endothelial keratoplasty. , 2013, Ophthalmology.

[54]  P. Robson,et al.  High Throughput Gene Expression Analysis Identifies Reliable Expression Markers of Human Corneal Endothelial Cells , 2013, PloS one.

[55]  G. Pellegrini,et al.  Limbal stem-cell therapy and long-term corneal regeneration. , 2010, The New England journal of medicine.

[56]  D. Böhringer,et al.  Costs and financing. A cost calculation of an up-to-date eye bank in Germany. , 2009, Developments in ophthalmology.

[57]  E. Fuchs,et al.  Regenerative medicine: An eye to treating blindness , 2010, Nature.

[58]  Marcus Ang,et al.  Descemet membrane endothelial keratoplasty , 2015, British Journal of Ophthalmology.

[59]  P. Mahadevan,et al.  An overview , 2007, Journal of Biosciences.

[60]  D. Maurice,et al.  Transplantation of tissue-cultured corneal endothelium. , 1978, Investigative ophthalmology & visual science.

[61]  J. Abendshien,et al.  Managing the Future , 1996 .

[62]  K. Goins,et al.  Eye bank survey of surgeons using precut donor tissue for descemet stripping automated endothelial keratoplasty. , 2008, Cornea.