Corneal Transplantation for Infectious Keratitis: A Prospective Dutch Registry Study.

PURPOSE: The aim of this study was to analyze real-world practice patterns and graft survival after corneal transplantation for infectious keratitis in the Netherlands. METHODS: All consecutive keratoplasties for infectious keratitis registered in the Netherlands Organ Transplant Registry were included. Graft survival was analyzed using Kaplan-Meier survival curves with Cox regression to compare the 3 most common pathogens with subgroup analysis for type and reason of transplantation, sex, and graft size. Multivariable analysis was performed using the same explanatory factors. RESULTS: Between 2007 and 2017, 1111 keratoplasties for infectious keratitis were registered in the Netherlands Organ Transplant Registry. The most common pathogens were viruses (n = 437), bacteria (n = 271), and Acanthamoeba (n = 121). Human leukocyte antigen (HLA) matching did not provide a significant survival benefit, whereas emergency procedures showed worse graft survival [hazard ratio (HR) = 0.40, P = 0.120; HR = 2.73, P < 0.001, respectively]. Graft size >8.5 mm was significantly worse than graft size 8.5 mm (HR = 2.062, P = 0.010). In therapeutic keratoplasty, graft survival was significantly worse for Acanthamoeba than viral keratitis (HR = 2.36, P = 0.008). In the multivariable model, adjusting for graft size, type, and reason for transplantation, viral and bacterial keratitis did not differ significantly in graft survival, and Acanthamoeba showed a significantly worse prognosis (vs. viral keratitis, HR = 2.30, P < 0.001; bacterial keratitis, HR = 2.65, P < 0.001). CONCLUSIONS: Viral keratitis was the most common indication for transplantation, followed by bacterial and Acanthamoeba keratitis. HLA matching did not offer protection over elective non-HLA-matched procedures, whereas emergency procedures and grafts sized >8.5 mm showed poor survival. In optical keratoplasty, survival is high for all pathogens, whereas in therapeutic keratoplasty Acanthamoeba shows poor outcome.

Trial-based cost-effectiveness analysis of Descemet membrane endothelial keratoplasty (DMEK) versus ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK).

PURPOSE: To evaluate the cost-effectiveness of Descemet Membrane Endothelial Keratoplasy (DMEK) versus Ultrathin Descemet Stripping Automated Endothelial Keratoplasty (UT-DSAEK). METHODS: A cost-effectiveness analysis using data from a multicenter randomized clinical trial was performed. The time horizon was 12 months postoperatively. Patients with Fuchs' endothelial dystrophy were randomized to DMEK (n = 29) or UT-DSAEK (n = 24). Relevant resources from healthcare and societal perspectives were included in the cost analysis. Quality-Adjusted Life Years (QALYs) were determined using the Health Utilities Index Mark 3 (HUI3) and the EuroQol EQ-5D-5L questionnaires. The main outcome was the incremental cost-effectiveness ratio (ICER; incremental societal costs per QALY). RESULTS: Societal costs averaged €8851 (US$11 406) for DMEK and €8320 (US$10 722) for UT-DSAEK. Higher costs in the DMEK group were mainly caused by higher rebubbling and regraft rates (21% and 7%, vs. 4% and 0% in the UT-DSAEK group). HUI3 QALYs were 0.70 (DMEK) and 0.79 (UT-DSAEK). EQ-5D-5L QALYs were 0.83 (DMEK) and 0.86 (UT-DSAEK). The ICER indicated DMEK was dominated by UT-DSAEK in both analyses. The cost-effectiveness probability for DMEK ranged from 21% to 5% (HUI3 QALYs) and 27%-14% (EQ-5D-5L QALYs), assuming the maximum acceptable ICER ranged from €2500 to €80.000 (US$3222-US$103 093) per QALY. CONCLUSION: The base case cost-effectiveness analysis favoured UT-DSAEK over DMEK, as costs of DMEK were higher while QALYs were lower. Further studies are required to assess long-term rebubbling and regraft rates and graft survival.

Practice patterns of corneal transplantation in Europe: first report by the European Cornea and Cell Transplantation Registry.

PURPOSE: To report practice patterns of corneal transplantation in Europe. SETTING: Corneal clinics in 10 European member states (MS), the United Kingdom, and Switzerland. DESIGN: Multinational registry study. METHODS: Corneal transplant procedures registered in the European Cornea and Cell Transplantation Registry were identified. Preoperative donor and recipient characteristics, indication and reason for transplantation, and surgical techniques were analyzed. RESULTS: A total of 12 913 corneal transplants were identified from 10 European Union MS, the United Kingdom, and Switzerland. Most countries were self-sufficient with regard to donor tissue. Fuchs endothelial corneal dystrophy was the most common indication (41%, n = 5325), followed by regraft (16%, n = 2108), pseudophakic bullous keratopathy (12%, n = 1594), and keratoconus (12%, n = 1506). Descemet stripping automated endothelial keratoplasty (DSAEK, 46%, n = 5918) was the most commonly performed technique, followed by penetrating keratoplasty (30%, n = 3886) and Descemet membrane endothelial keratoplasty (9%, n = 1838). Vision improvement was the main reason for corneal transplantation (90%, n = 11 591). Surgical technique and reason for transplantation differed between indications. CONCLUSIONS: This report provides the most comprehensive overview of corneal transplantation practice patterns in Europe to date. Fuchs endothelial dystrophy is the most common indication, vision improvement the leading reason, and DSAEK the predominant technique for corneal transplantation.

Quality of vision and vision-related quality of life after Descemet membrane endothelial keratoplasty: a randomized clinical trial.

PURPOSE: To compare quality of vision and vision-related quality of life (QOL) in patients undergoing Descemet membrane endothelial keratoplasty (DMEK) or ultrathin Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: Fifty-four eyes of 54 patients with Fuchs' dystrophy from six corneal clinics in the Netherlands were randomized to DMEK or ultrathin DSAEK and examined preoperatively, and 3, 6 and 12 months postoperatively. Main outcome measures were corneal higher-order aberrations (HOAs), contrast sensitivity, straylight and vision-related QOL. RESULTS: Posterior corneal HOAs decreased after DMEK and increased after ultrathin DSAEK (p ≤ 0.001) 3 months after surgery and correlated positively with best spectacle-corrected visual acuity (12 months: r = 0.29, p = 0.04). Anterior and total corneal HOAs did not differ significantly between both techniques at any time point. Contrast sensitivity was better (p = 0.01), and straylight was lower (p = 0.01) 3 months after DMEK compared with ultrathin DSAEK; 95% confidence interval [CI] of log(cs) 1.10-1.35 versus 95% CI: 0.84 to 1.12, and 95% CI: log(s) 1.18 to 1.43 versus 95% CI: 1.41 to 1.66, respectively. Both were comparable at later time points. Vision-related QOL (scale 0-100) did not differ significantly between both groups at any time point and improved significantly at 3 months (ß = 12 [95% CI: 7 to 16]; p < 0.001), and subsequently between 3 and 12 months (ß = 5 [95% CI: 0 to 9]; p = 0.06). CONCLUSIONS: Descemet membrane endothelial keratoplasty (DMEK) results in lower posterior corneal HOAs compared with ultrathin DSAEK. Contrast sensitivity and straylight recover faster after DMEK but reach similar levels with both techniques at 1 year. Vision-related QOL improved significantly after surgery, but did not differ between both techniques.

Outcomes of corneal transplantation in Europe: report by the European Cornea and Cell Transplantation Registry.

PURPOSE: To analyze real-world graft survival and visual acuity outcomes of corneal transplantation in Europe. SETTING: Corneal clinics in 10 European Union member states, the United Kingdom, and Switzerland. DESIGN: Multinational registry study. METHODS: All corneal transplant procedures registered in the European Cornea and Cell Transplantation Registry (ECCTR) were identified. Graft survival of primary corneal transplants were analyzed using Kaplan-Meier survival curves with log-rank test and Cox regression. Corrected distance visual acuities (CDVAs) are reported at baseline and 2 years postoperatively using the Lundström distribution matrix. RESULTS: A total of 12 913 corneal transplants were identified. Overall, 32-year graft survival of corneal transplants was high (89%) but differed between indications, ranging from 98% in keratoconus and 80% for trauma. Overall, CDVA improved postoperatively, but the risk for losing vision ranged from 7% (baseline vision ≤0.1 Snellen) to 58% (baseline vision ≥1.0 Snellen). CONCLUSIONS: This report provides a comprehensive overview of graft survival and visual outcomes of corneal transplantation in Europe. In addition, it provides real-world estimates of outcomes for a variety of indications and surgical techniques to support benchmarking and demonstrates the relationship between baseline and postoperative vision.

New Technologies in Clinical Trials in Corneal Diseases and Limbal Stem Cell Deficiency: Review from the European Vision Institute Special Interest Focus Group Meeting.

To discuss and evaluate new technologies for a better diagnosis of corneal diseases and limbal stem cell deficiency, the outcomes of a consensus process within the European Vision Institute (and of a workshop at the University of Cologne) are outlined. Various technologies are presented and analyzed for their potential clinical use also in defining new end points in clinical trials. The disease areas which are discussed comprise dry eye and ocular surface inflammation, imaging, and corneal neovascularization and corneal grafting/stem cell and cell transplantation. The unmet needs in the abovementioned disease areas are discussed, and realistically achievable new technologies for better diagnosis and use in clinical trials are outlined. To sum up, it can be said that there are several new technologies that can improve current diagnostics in the field of ophthalmology in the near future and will have impact on clinical trial end point design.

Real-World Outcomes of DMEK: A Prospective Dutch registry study.

PURPOSE: This study analyzed real-world practice patterns, graft survival, and outcomes of Descemet membrane endothelial keratoplasty (DMEK) in the Netherlands. DESIGN: Population-based interventional clinical study. METHODS: In this prospective registry study, all consecutive primary DMEK procedures registered in the Netherlands Organ Transplant Registry were identified. Short-term graft survival and outcomes of primary transplants for Fuchs' endothelial dystrophy (FED) were analyzed using Kaplan-Meier survival curves with log-rank test and Cox regression. Linear mixed model analyses were used for best spectacle-corrected visual acuity (BSCVA), spherical equivalent, hyperopic shift, and endothelial cell density. RESULTS: 752 DMEKs were identified between 2011 and 2018. In 90% of cases, the indication for DMEK was FED. Graft survival measured 87% at 3 months, 85% at 6 months, 85% at 1 year, and 78% at 2 years. DMEK procedures after 2015 showed better survival compared to previous years (Hazard ratio = 0.4; P < .001). Baseline BSCVA in primary transplants with FED measured on average 0.45 logarithm of the minimum angle of resolution (logMAR) (95% confidence interval [CI], 0.41-0.49), and significantly improved (overall P < .001) to 0.17 logMAR (95% CI, 0.14-0.21) at 3 months, 0.15 logMAR (95% CI, 0.11-0.18) at 6 months, 0.12 logMAR (95% CI, 0.08-0.16) at 1 year, and 0.08 (95% CI, 0.05-0.12) at 2 years. At 3 months, a hyperopic shift of +0.36 diopters (P < .001) was observed and endothelial cell loss measured 33%. CONCLUSION: Our findings provide real-world support that DMEK is an effective treatment for FED with respect to vision restoration, inducing a small hyperopic shift with an acceptable endothelial cell loss. Graft survival improved over time, suggesting a learning curve on a national level.

Descemet Membrane Endothelial Keratoplasty versus Ultrathin Descemet Stripping Automated Endothelial Keratoplasty: A Multicenter Randomized Controlled Clinical Trial.

PURPOSE: To compare best spectacle-corrected visual acuity (BSCVA), endothelial cell density (ECD), refractive astigmatism, and complications after Descemet membrane endothelial keratoplasty (DMEK) and ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK). DESIGN: Prospective, multicenter randomized controlled trial. PARTICIPANTS: Fifty-four pseudophakic eyes of 54 patients with corneal endothelial dysfunction resulting from Fuchs endothelial corneal dystrophy were enrolled in 6 corneal centers in The Netherlands. METHODS: Participants were allocated to DMEK (n = 29) or UT-DSAEK (n = 25) using minimization randomization based on preoperative BSCVA, recipient central corneal thickness, gender, age, and institution. Donor corneas were prestripped and precut for DMEK and UT-DSAEK, respectively. Six corneal surgeons participated in this study. MAIN OUTCOME MEASURES: The primary outcome measure was BSCVA at 12 months after surgery. RESULTS: Central graft thickness of UT-DSAEK lamellae measured 101 µm (95% confidence interval [CI], 90-112 µm). Best spectacle-corrected visual acuity did not differ significantly between DMEK and UT-DSAEK groups at 3 months (0.15 logarithm of the minimum angle of resolution [logMAR] [95% CI 0.08-0.22 logMAR] vs. 0.22 logMAR [95% CI 0.16-0.27 logMAR]; P = 0.15), 6 months (0.11 logMAR [95% CI 0.05-0.17 logMAR] vs. 0.16 logMAR [95% CI 0.12-0.21 logMAR]; P = 0.20), and 12 months (0.08 logMAR [95% CI 0.03-0.14 logMAR] vs. 0.15 logMAR [95% CI 0.10-0.19 logMAR]; P = 0.06). Twelve months after surgery, the percentage of eyes reaching 20/25 Snellen BSCVA was higher in DMEK compared with UT-DSAEK (66% vs. 33%; P = 0.02). Endothelial cell density did not differ significantly 12 months after DMEK and UT-DSAEK (1870 cells/mm2 [95% CI 1670-2069 cells/mm2] vs. 1612 cells/mm2 [95% CI 1326-1898 cells/mm2]; P = 0.12). Both techniques induced a mild hyperopic shift (12 months: +0.22 diopter [D; 95% CI -0.23 to 0.68 D] for DMEK vs. +0.58 D [95% CI 0.13-1.03 D] for UT-DSAEK; P = 0.34). CONCLUSIONS: Descemet membrane endothelial keratoplasty and UT-DSAEK did not differ significantly in mean BSCVA, but the percentage of eyes achieving 20/25 Snellen vision was significantly higher with DMEK. Endothelial cell loss did not differ significantly between the treatment groups, and both techniques induced a minimal hyperopic shift.

Safety and Comfort of an Innovative Drug Delivery Device in Healthy Subjects.

Purpose: The aim of this study was to investigate safety and comfort of two versions of a placebo-microsphere filled ocular coil (straight and curved) in healthy subjects. Methods: The study was a single-center intervention study. One ocular coil was placed in the inferior conjunctival fornix for the intended duration of 28 days. Forty-two healthy adult subjects were included. At baseline, 30 minutes, 8 hours, 24 hours, 48 hours, 7 days, 14 days, 21 days, and 28 days after insertion, examinations were performed, including slit lamp evaluation to score ocular redness, intraocular pressure measurement, visual acuity, tear secretion test, and questionnaires. Results: The straight and curved ocular coils had a median retention time of 5 days and 12 days, respectively. After 48 hours, 57% and 81% subjects retained the straight and curved ocular coil, respectively. Four (19%) subjects with the straight coil and six (29%) with the curved coil completed the entire study period. Minor changes in ocular hyperemia were observed in both groups. On day 7, the straight coil was more comfortable than the curved coil with a visual analogue scale (VAS) score of 77 ± 21 compared to 94 ± 11 (P = 0.028), respectively. No other ocular adverse events were observed. Conclusions: Comfort and safety of the straight and curved ocular coil are high. Because the retention time is too short for long-term sustained drug release, the use in the perioperative or immediate postoperative period could prove to be more valuable. Translational Relevance: The ocular coil is a noninvasive, comfortable and safe short-term drug delivery device.

Long-term Outcomes of Repeated Corneal Transplantations: A Prospective Dutch Registry Study.

PURPOSE: To compare long-term outcomes of repeated corneal transplantations (CT), based on primary indication (Fuchs endothelial dystrophy [FED] vs pseudophakic bullous keratoplasty [PBK]), surgical technique (penetrating keratoplasty [PK] vs endothelial keratoplasty [EK]), and indication for repeated grafting. METHODS: In this nonrandomized treatment comparison with national registry data (Netherlands Organ Transplantation Registry, NOTR), data on all consecutive repeated CT following primary PK or EK for FED and PBK between 1994 and 2015 were analyzed, with a maximal follow-up of 5 years. Regraft survival was analyzed using Kaplan-Meier survival curves and univariable and multivariable Cox regression analysis. Secondary outcomes best-corrected visual acuity, spherical equivalent, and refractive astigmatism were compared using linear mixed-model analysis. RESULTS: A total of 332 repeated CT were analyzed. The number of regrafts increased significantly between 2007 and 2015 (P = .001). Overall 5-year regraft survival was 60% and was higher for FED vs PBK (77% vs 45%, HR = 0.40, P = .001), and re-EK vs re-PK (81% vs 55%, HR = 0.51, P = .041). However, multivariable analysis showed no significant difference in survival based on primary indication, surgical technique, and indication for regrafting. Corrected for baseline, secondary outcomes also did not differ between groups. CONCLUSIONS: We found a significant increase in repeated CT, coinciding with the introduction of EK in the Netherlands. While univariable analysis suggested better overall regraft survival for FED and (re-)EK, multivariable analysis showed no such difference. This may be owing to allocation of favorable cases to undergo (re-)EK. Similarly, secondary outcomes were determined by the primary CT technique.