This thesis focuses on the clinical outcomes after Descemet membrane endothelial keratoplasty (DMEK). Chapter 2 describes the suitability of septic donor corneas for transplantation and the... Show moreThis thesis focuses on the clinical outcomes after Descemet membrane endothelial keratoplasty (DMEK). Chapter 2 describes the suitability of septic donor corneas for transplantation and the clinical outcomes after DMEK using septic versus non-septic donor corneas. Chapter 3 aims to analyze the incidence of cataract extraction in eyes that previously underwent DMEK surgery and the effect of the phacoemulsification procedure on the endothelial cell density (ECD) after DMEK. Chapter 4 of the thesis concentrates on the 6-month ECD after DMEK, as it is one of the benchmark parameters for graft performance. In this chapter, the relation between the ECD 6 months after DMEK and its predictive value for 5-year graft survival in FECD eyes are discussed. Chapter 5 evaluates the 10-year graft survival and clinical outcome results of the first 100 eyes that received DMEK. Chapter 6 presents a larger case series of DMEK eyes where the 10-year clinical outcomes and graft survival after DMEK are analyzed based on the surgical indication of the eye and the preoperative severityof FECD. Show less
The thesis focuses on the in vivo and in vitro behavior of corneal endothelial cells before and after endothelial keratoplasty. The first part of the project concentrates on the ECD decrease after... Show moreThe thesis focuses on the in vivo and in vitro behavior of corneal endothelial cells before and after endothelial keratoplasty. The first part of the project concentrates on the ECD decrease after DMEK and DMEK graft viability prior to transplantation. The second part focusses on regenerative strategies for the treatment of FECD by developing and applying in vitro cell migration assays. In vitro cell migration from DMEK grafts of various sizes and shapes are investigated in a 3D cell culture system aiming to identify critical parameters for the successful clinical application of corneal endothelial therapies. Show less
Vasiliauskaite, I.; Quilendrino, R.; Baydoun, L.; Dijk, K. van; Melles, G.R.J.; Oellerich, S. 2021
Purpose: To analyze if 6-month endothelial cell density (ECD) affects long-term ECD outcome and graft survival 5 years after Descemet membrane endothelial keratoplasty (DMEK) in eyes with Fuchs... Show morePurpose: To analyze if 6-month endothelial cell density (ECD) affects long-term ECD outcome and graft survival 5 years after Descemet membrane endothelial keratoplasty (DMEK) in eyes with Fuchs endothelial corneal dystrophy (FECD).Design: Retrospective cohort study.Participants: A total of 585 DMEK eyes were included. The study group was divided into 4 groups based on 6-month ECD quartiles: group 1 (n = 146) with 313 to 1245 cells/mm(2), group 2 (n = 148) with 1246 to 1610 cells/mm(2), group 3 (n = 145) with 1611 to 1938 cells/mm(2), and group 4 (n = 146) with 1939 to 2760 cells/mm(2). Group 1 was further split into subgroups 1a (n = 36) with 6-month ECD of <828 cells/mm(2), 1b (n = 37) with 829 to 1023 cells/mm(2), 1c (n = 37) with 1024 to 1140 cells/mm(2), and 1d (n = 36) 1141 to 1245 cells/mm(2).Methods: Descemet membrane endothelial keratoplasty.Main Outcome Measures: Long-term ECD, graft survival, and postoperative complication rates.Results: For group 1, 6-month ECD decreased from 951 (+/- 233) cells/mm(2) (n = 146) to 735 (+/- 216) cells/mm(2) (n = 99) at 5 years postoperatively. Group 1 graft survival probability was 0.95 (95% confidence interval [CI], 0.91-0.99] at 5 years postoperatively, which was lower than for groups 2 to 4 (P = 0.001). Five-year graft survival in subgroup 1a was 0.79 (95% CI, 0.67-0.94), which was lower than in subgroups 1b to 1d (P = 0.001). Preoperative ECD did not influence graft survival (P = 0.400), and higher 6-month ECD values were associated with lower graft failure rates (hazard ratio, 0.994; 95% CI, 0.99-1.00; P = 0.001).Conclusions: Six-month ECD is associated with DMEK graft survival. High early cell loss after DMEK negatively affects long-term ECD outcome and graft survival. Grafts in the lowest 6-month ECD subgroup (<828 cells/mm(2)) are at higher risk of failure within 5 years after DMEK. To ensure sufficiently high 6-month ECD, preoperative graft quality assessment should be optimized, and cellular stress induced to the graft should be minimized. Additionally, developing therapeutic options for the treatment of low postoperative ECD could further improve DMEK graft longevity. (C) 2021 by the American Academy of Ophthalmology Show less
Corneal diseases are among the leading causes of reversible blindness worldwide. When conservative treatment options fail, many eyes can be treated with corneal transplantation. Historically, full... Show moreCorneal diseases are among the leading causes of reversible blindness worldwide. When conservative treatment options fail, many eyes can be treated with corneal transplantation. Historically, full thickness corneal transplantation, in which all corneal layers are replaced, has been the mainstay of care in the treatment of corneal endothelial disorders. In the past two decades, however, there has been a trend towards the selective, less invasive replacement of only the diseased, rather than all corneal layers. These partial thickness corneal transplantations are known as lamellar keratoplasties. Lamellar keratoplasty has significantly improved the clinical outcomes, such as visual acuity, after transplantation. Since its introduction in 1998, lamellar keratoplasty has evolved from Deep lamellar endothelial keratoplasty to Descemet membrane endothelial keratoplasty (DMEK). Globally, however, there is only one donor cornea available for 70 people in need. This shortage inspired further refinement of conventional DMEK and led to the development of adapted DMEK-techniques, which may increase the availability of endothelial donor grafts. This thesis focuses on donor tissue preparation for DMEK and evaluates the feasibility and clinical outcomes of DMEK, DMET, Hemi-DMEK and Quarter-DMEK in the management of corneal endothelial disorders. Show less
Quarter-Descemet membrane endothelial keratoplasty (Quarter-DMEK) has been introduced as a modification of the standard DMEK technique to increase the pool of endothelial grafts. In this study, we... Show moreQuarter-Descemet membrane endothelial keratoplasty (Quarter-DMEK) has been introduced as a modification of the standard DMEK technique to increase the pool of endothelial grafts. In this study, we evaluated in vitro changes in endothelial cell distribution, viability and morphology of Quarter-DMEK grafts when stored in organ-culture medium. Quarter-DMEK grafts were prepared from 5 corneas and stored in organ-culture medium for 4, 7 and 11 days. Endothelial cell re-distribution was investigated by light microscopy, cell viability by a Calcein-AM assay, and expression of endothelial and non-endothelial markers by immunohistochemistry. Three standard DMEK-grafts were used as controls. After preparation, all Quarter-DMEK grafts showed a band with no viable endothelial cells along the radial cut graft edges [average width 190 (+/- 20) mu m]. Endothelial cell density in the central graft area decreased by 12%, 23% and 26% after 4, 7, and 11 days of storage, respectively. At the same time, empty bands along the cut edges were re-populated and some cells migrated to the stromal side of the Descemet membrane (DM). These cells showed an altered phenotype, as indicated by expression of migration marker CD73 and fibroblast marker alpha SMA. Majority of migration occurred within the first 4 days of storage. Our data suggest that endothelial cells on Quarter-DMEK grafts re-distribute during organ-culture storage to re-populate preparation-induced empty bands and after re-distribution, cells may show further migration to the stromal DM side during storage. Show less
Baydoun, L.; Bruinsma, M.; Santander-Garcia, D.; Ham, L.; Oellerich, S.; Melles, G.R.J. 2020
Purpose To assess whether combined analysis of specular microscopy and Scheimpflug imaging improves detection of an upcoming allograft rejection following Descemet membrane endothelial keratoplasty... Show morePurpose To assess whether combined analysis of specular microscopy and Scheimpflug imaging improves detection of an upcoming allograft rejection following Descemet membrane endothelial keratoplasty (DMEK).Methods Retrospective analysis of 22 eyes that had developed a clinical proven allograft rejection 28 (+/- 22) months (range: 4-84 months) after DMEK. Specular microscopy and Scheimpflug images routinely made after DMEK were retrospectively analysed for changes in endothelial cell morphology (e.g. nuclear activation), cell density (>10%) and pachymetry (>7%), and/or the presence of subclinical keratic precipitates. The same parameters were evaluated for 22 control eyes matched for age, gender and surgery indication.Results A total of 20/22 eyes (91%) showed detectable changes 0.25-75 months before allograft rejection became clinically manifest: 13/22 (59%) showed both specular microscopy and Scheimpflug imaging changes; 5/22 (23%) only had changes on Scheimpflug imaging; and 2/22 (9%) only had specular microscopy changes. In 18/22 (82%) and 14/22 (64%) eyes, subclinical keratic precipitates and endothelial cell morphology changes could be detected, respectively. A total of 11/22 (50%) eyes concurrently showed a >10% drop in endothelial cell density and 4/22 (18%) a >7% pachymetry increase. Of the control eyes, 7/22 (32%) showed changes with specular microscopy but not with Scheimpflug imaging.Conclusions Combined analysis of specular microscopy and Scheimpflug imaging may allow recognizing an upcoming allograft rejection in over 90% of eyes and up to 6 years before rejection becomes clinically manifest. Early recognition of eyes at risk may allow for targeted intensified steroid treatment to prevent endothelial cell damage associated with rejection. Show less
Since 1998, various new surgical techniques have been devised for the treatment of diseases of the anterior and posterior cornea; this thesis explores some of these options including Descemet... Show moreSince 1998, various new surgical techniques have been devised for the treatment of diseases of the anterior and posterior cornea; this thesis explores some of these options including Descemet Membrane Endothelial Keratoplasty (DMEK) and Bowman Layer Transplantation. Show less
Parker, J.; Krijgsman, M.; Dijk, K. van; Melles, G.R.J. 2017
