Economic evaluation of endothelial keratoplasty techniques and penetrating keratoplasty in the Netherlands.

PURPOSE: To evaluate cost-effectiveness of penetrating keratoplasty (PK), femtosecond laser-assisted Descemet stripping endothelial keratoplasty (FS-DSEK), and Descemet stripping automated endothelial keratoplasty (DSAEK). DESIGN: Cost-effectiveness analysis based on data from a randomized multicenter clinical trial and a noncomparative prospective study. METHODS: Data of 118 patients with corneal endothelial dysfunction were analyzed in the economic evaluation. Forty patients were included in the PK group, 36 in the FS-DSEK group, and 42 in the DSAEK group. The primary incremental cost-effectiveness ratio (ICER) was the incremental costs per clinically improved patient, defined as a patient with a combined effectiveness of both a clinically improved BSCVA (defined as an improvement of at least 2 lines) and a clinically acceptable refractive astigmatism (defined as less than or equal to 3.0 diopters). Analysis was based on a 1-year follow-up period after transplantation. RESULTS: The percentage of treated patients who met the combined effectiveness measures was 52% for DSAEK, 44% for PK, and 43% for FS-DSEK. Mean total costs per patient were €6674 (US$7942), €12 443 (US$14 807), and €7072 (US$8416) in the PK group, FS-DSEK group, and DSAEK group, respectively. FS-DSEK was less effective and more costly compared to both DSAEK and PK. DSAEK was more costly but also more effective compared to PK, resulting in incremental costs of €4975 (US$5920) per additional clinically improved patient. CONCLUSIONS: The results of this study show that FS-DSEK was not cost-effective compared to PK and DSAEK. DSAEK, on the other hand, was more costly but also more effective compared to PK. Including societal costs, a longer follow-up period and preparation of the lamellar transplant buttons in a national cornea bank could improve the cost-effectiveness of DSAEK.

Quality of vision after femtosecond laser-assisted descemet stripping endothelial keratoplasty and penetrating keratoplasty: a randomized, multicenter clinical trial.

PURPOSE: To compare the quality of vision (straylight and contrast sensitivity) after femtosecond laser-assisted Descemet stripping endothelial keratoplasty (FS DSEK) and penetrating keratoplasty (PK). DESIGN: Prospective, randomized clinical trial. METHODS: setting: Multicenter (5 ophthalmic centers in The Netherlands). study population: Eighty eyes of 80 patients with corneal endothelial dysfunction were included and were randomized to FS DSEK or PK. observation procedures: FS DSEK and PK. main outcome measures: Straylight, contrast sensitivity, astigmatism, uncorrected visual acuity, best spectacle-corrected visual acuity (BSCVA), and visual symptom score. RESULTS: Straylight at 12 months was 1.37 ± 0.2 logarithm of straylight for FS DSEK and 1.46 ± 0.2 logarithm of straylight for PK (P = .151). During 12 months of follow-up, there was a significant improvement of straylight and contrast sensitivity after FS DSEK (P < .001) and PK (P < .001). The change of straylight and contrast sensitivity correlated significantly with the change of BSCVA after FS DSEK (r = -0.645; r = 0.580) and PK (r = -0.370; r = 0.659). The visual symptom score was comparable between the 2 groups during the 12 months of follow-up. CONCLUSIONS: Improvement of straylight and contrast sensitivity was significantly correlated with an improvement of BSCVA. Straylight and contrast sensitivity were improved significantly after FS DSEK and were comparable with those after PK, although BSCVA was slightly better in the PK group.

Economic evaluation of deep anterior lamellar keratoplasty versus penetrating keratoplasty in The Netherlands.

PURPOSE: To evaluate the cost effectiveness of deep anterior lamellar keratoplasty (DALK) versus penetrating keratoplasty (PK) in The Netherlands. DESIGN: Cost-effectiveness analysis alongside a randomized, multicenter clinical trial. METHODS: Fifty-three patients with corneal stromal pathologic features not affecting the endothelium were included with 28 patients in the DALK group and 25 in the PK group. Quality of life was measured before surgery and 3, 6, and 12 months after surgery. The main outcome measures were incremental cost-effectiveness ratios per clinically improved patient on the 25-item National Eye Institute Visual Functioning Questionnaire and per patient with endothelial cell loss of maximally 20% within the first year. RESULTS: Mean total bootstrapped costs per patient were €7607 (US$10,498) in the DALK group and €6552 (US$9042) in the PK group. The incremental cost-effectiveness ratios were €9977 (US$13,768) per clinically improved patient on the 25-item National Eye Institute Visual Functioning Questionnaire and €6900 (US$9522) per patient with cell loss of maximally 20%. In patients without perforation of the Descemet membrane, the incremental cost-effectiveness ratio was €5250 (US$7245) per patient. CONCLUSIONS: This study shows that DALK is more costly and more effective as compared with PK. Results on the 25-item National Eye Institute Visual Functioning Questionnaire were in favor of DALK, and endothelial cell loss in DALK patients remained stable after 6 months, whereas cell loss in PK patients continued. Furthermore, DALK procedures performed without perforation of the Descemet membrane were more effective. However, because it is unknown what society is willing to pay for an additional improved patient, cost effectiveness of DALK within a limited follow-up period of 12 months is unclear. Cost effectiveness of DALK may improve over time because of lower graft failure.

Endothelial cell loss and visual outcome of deep anterior lamellar keratoplasty versus penetrating keratoplasty: a randomized multicenter clinical trial.

OBJECTIVE: To compare endothelial cell (EC) loss, visual and refractive outcomes, and complications after deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PK). DESIGN: Randomized, multicenter clinical trial. PARTICIPANTS: Fifty-six eyes of 56 patients with a corneal stromal pathology not affecting the endothelium were randomized to DALK or PK. METHODS: The DALK procedure was performed according to Anwar's big-bubble technique. Patients underwent an ophthalmic examination preoperatively and 3, 6, and 12 months postoperatively. MAIN OUTCOME MEASURES: Endothelial cell loss, refractive and topographic astigmatism, spherical equivalent, uncorrected visual acuity, and best spectacle-corrected visual acuity (BSCVA) were measured, and complications were recorded. RESULTS: Endothelial cell loss was significantly higher after PK compared with DALK procedures performed without perforation of Descemet's membrane (12 months: 27.7% ± 11.1% vs. 12.9% ± 17.6%). The BSCVA was significantly better in the PK group at 3 and 6 months after surgery but was not significantly different 12 months after surgery (0.39 ± 0.3 logarithm of the minimum angle of resolution [logMAR] in DALK and 0.31 ± 0.3 logMAR in PK). At 12 months postoperatively, refractive and topographic astigmatism in the DALK and PK groups were -3.37 ± 2.3 diopters (D) and -3.76 ± 2.1 D (P = 0.53), and 3.57 ± 2.3 D and 4.16 ± 2.0 D (P = 0.34), respectively. (Micro)perforation of the Descemet's membrane occurred in 32% (9/28) of the DALK eyes, and 18% (5/28) of the patients required conversion to PK. Endothelial cell loss was not significantly different between DALK and PK when cases with perforation of Descemet's membrane were included in the (intention-to-treat) analysis (12 months: 19.1 ± 21.6 vs. 27.7 ± 11.1 P = 0.112). Rejection episodes were reported in 1 patient in the DALK group (epithelial rejection) and 3 patients in the PK group (all endothelial rejections). No graft failure occurred. CONCLUSIONS: One year after DALK performed without perforation of Descemet's membrane, EC loss is significantly lower, whereas the BSCVA is comparable to that in the PK group. In addition, no endothelial rejection occurred in the DALK group. However, Descemet's membrane perforation remains a major complication in DALK and warrants improvements to standardize the big-bubble technique.

Validation of tissue quality parameters for donor corneas, designated for emergency cases: corneal graft survival.

PURPOSE: To validate tissue quality parameters for donor corneas designated for emergency grafting for corneal graft survival. METHODS: In a longitudinal cohort follow-up study, 131 emergency penetrating grafts were studied. Grafts were performed with a pool of organ-cultured donor corneas designated for emergency grafting and prepared for immediate use with all safety tests performed. Assignation criteria were: corneas with a small superficial stromal opacity but meeting all selection criteria for PKP tissue and corneas without stromal opacity, but an endothelial cell density from 1800 to 2300 cells/mm(2) or mild polymegathism or pleomorphism. Cox multivariate regression analysis, Kaplan-Meier survival and log rank test were applied. RESULTS: Of the 131 keratoplasties, 115 could be followed. One eye was lost during surgery because of an expulsive bleeding. In 15 cases, a conjunctival transplantation finished off the penetrating graft. Corneal graft survival was not significantly related to the presence of PKP quality of the donor endothelium, neither with a cloudy graft nor with endothelial decompensation as the cause of failure. Main risk factors for a failed graft were vascularization of the host cornea (p=0.0001), the presence of a systemic auto immune disease in the recipient (p=0.003) and the disease leading to the (imminent) perforation and emergency graft (p=0.021). CONCLUSION: A selected pool of donor corneas designated for emergency grafting that does not interfere with the scheduled procedures allows more efficient and safe use of donor tissue in case of a(n) (imminent) perforation. Corneal graft survival rates justify the criteria for selection.

Validation of tissue quality parameters for donor corneas designated for emergency use in preservation of the globe.

PURPOSE: To validate tissue quality parameters for donor corneas designated for emergency grafting to preserve the globe. METHODS: In a longitudinal cohort follow-up study, 151 emergency grafts in the Netherlands were studied. Grafts were performed with a pool of organ-cultured donor corneas designated for emergency grafting and prepared for immediate use with all safety tests performed. Assignation criteria were corneas with a small superficial stromal opacity but meeting all selection criteria for penetrating keratoplasty tissue and corneas without stromal opacity but an endothelial cell density from 1800 to 2300 cells per square millimeter or mild polymegethism or pleomorphism. Cox multivariate regression analysis, Kaplan-Meier survival, and log rank test were applied. RESULTS: All requests for corneal tissue were honored within 24 hours. Ninety-one patients showed a complete and 60 an imminent perforation. One hundred thirty-one penetrating grafts and 20 lamellar grafts have been used. The globes were saved in 140 of the 151 patients (92.7%). Globe preservation was not significantly related to the absence of penetrating keratoplasty quality of the donor endothelium, the type of grafting, the degree of vascularization in the host cornea, or diabetic disease in the recipient. The main risk factor for globe preservation was the presence of a systemic autoimmune disease in the recipient (P = 0.0021). CONCLUSIONS: A selected pool of donor corneas designated for emergency grafting, that does not interfere with the scheduled procedures, allows more efficient and safe use of donor tissue in case of an imminent perforation. Globe preservation rates justify the quality criteria for designation of this tissue.

Efficacy and safety of femtosecond laser-assisted corneal endothelial keratoplasty: a randomized multicenter clinical trial.

BACKGROUND: To evaluate the efficacy and safety of femtosecond laser-assisted endothelial keratoplasty (FLEK) versus penetrating keratoplasty (PK) in patients with corneal endothelial disease. METHODS: A randomized multicenter clinical trial of 80 eyes of 80 patients with corneal endothelial disease were randomized to FLEK or PK. Clinical outcomes (astigmatism and visual acuity) and incidence of postoperative complications were compared between the two groups. RESULTS: At 12 months, the percentage of eyes with a refractive astigmatism less than or equal to 3 diopters was higher in the FLEK group in comparison with the PK group (86.2% vs. 51.3%, P=0.004). The mean postoperative best corrected visual acuity was 20/70+/-2 lines in the FLEK group and 20/44+/-2 lines in the PK group (P<0.001), but the gain in the best corrected visual acuity between the two groups was not significantly different. The endothelial cell loss in the FLEK and PK group was 65+/-12% and 23+/-15% (P<0.001). The most common postoperative complication in the FLEK group was graft dislocation (27.8%). Wound healing related problems occurred in six eyes (15%) in the PK group and in none of the FLEK eyes. CONCLUSIONS: FLEK effectively reduces postoperative astigmatism and results in an absence of wound healing related problems in patients with endothelial disease. However, visual acuity is lower as compared with conventional PK, and the high level of endothelial cell loss warrants a modification of the insertion technique of the endothelial graft.

Five-year follow-up on the effect of oral acyclovir after penetrating keratoplasty for herpetic keratitis.

PURPOSE: To investigate the long-term effect of oral acyclovir administered during the first 6 months after penetrating keratoplasty (PK) for herpetic eye disease (HED). METHODS: A 5-year follow-up was undertaken for a patient population from a placebo-controlled, randomized trial on acyclovir prophylaxis after keratoplasty. In this former study the effectiveness of oral acyclovir prophylaxis was significant during the first 2 years after keratoplasty. Prospective data such as graft survival, graft clarity, vascularization, infective events, and rejection episodes were obtained from the national keratoplasty follow-up registry. Additional clinical data were derived from the medical charts. RESULTS: For 47 of the original 63 enrolled patients, the 5-year follow-up was completed. Comparing the acyclovir group with the placebo group, we found that with regard to the cumulative clinically evident recurrences, there was a statistically significant lower monthly event rate in the acyclovir group (P = 0.037). There were no statistically significant differences in visual acuity or in the use of oral aciclovir between the two treatment groups. The incidences of graft failure, vascularization, and medication or surgery for glaucoma were too low to analyze differences between the two groups. CONCLUSION: The results of our study suggest that oral acyclovir prescribed during the first 6 months after PK for HED protects against clinically evident HED recurrences during the first 5 years following PK.

Preliminary results of femtosecond laser-assisted descemet stripping endothelial keratoplasty.

OBJECTIVE: To evaluate the preliminary visual results of femtosecond laser-assisted Descemet stripping endothelial keratoplasty (FS-DSEK). METHODS: We prospectively analyzed results of 20 consecutive patients with Fuchs endothelial dystrophy or aphakic/pseudophakic bullous keratopathy who underwent FS-DSEK. Best spectacle-corrected visual acuity (BSCVA), refraction, corneal topography, and endothelial cell density were measured preoperatively and 3 and 6 months after FS-DSEK. Corneal thickness was measured using an optical coherence tomography technique. RESULTS: The average BSCVA of 11 eyes with normal visual potential significantly improved from 20/110 +/- 4 lines to 20/57 +/- 1 line at 6 months (P < .007). At 6 months, the mean (SD) hyperopic shift was 2.24 (2.3) diopters (D). Preoperative and 6 months postoperative refractive astigmatism were -0.75 (0.9) D and -1.58 (1.1) D (P = .01), but the topographic astigmatism did not change postoperatively (P = .95). Mean (SD) endothelial cell density at 6 months was 1368 (425) cells/mm(2). There was a persistent deswelling of the graft up to 3 months postoperatively. Complications included graft dislocations requiring repositioning (20%), pupillary block glaucoma (5%), epithelial ingrowth (5%), and primary graft failure (5%). CONCLUSIONS: Femtosecond laser-assisted Descemet stripping endothelial keratoplasty was effective in treating endothelial failure with minimal induced refractive astigmatism, limited improvement of BSCVA, and induction of a hyperopic shift. Endothelial cell count and dislocation rate were significant, which may be related to the surgical technique.

Prospective clinical evaluation of McCarey-Kaufman and organ culture cornea preservation media: 14-year follow-up.

PURPOSE: To compare the outcome of corneal grafts preserved in McCarey-Kaufman (MK) medium versus organ culture after penetrating keratoplasties. METHODS: Paired corneas were stored in McCarey medium for 2-44 hours (mean 21 hours) and in organ culture (OC) for 144 -240 hours (mean 192 hours). Penetrating keratoplasties were performed by 2 surgeons in 2 groups of patients with keratoconus, matched for age. Each pair was transplanted by the same surgeon using the same technique. Visual acuity, central corneal thickness, and central endothelial cell density were assessed at 166 +/- 7.8 months postoperatively. RESULTS: Nine pairs of patients were recovered for a long-term follow-up. The mean endothelial cell densities for the MK and OC groups were 611 +/- 155 and 683 +/- 168 cells/mm, respectively, which were not significantly different. A first rapid cell loss rate of 2.07% and 2.52% per month and a second slow of 0.78% and 0.69% per month were observed in the respective groups. Individual values of best corrected visual acuity were all the same (value 1.00) for both groups. Corneal thicknesses were, respectively, 571 +/- 52 and 540 +/- 35 microm and were significantly different (P = 0.013). CONCLUSIONS: After 14 years of penetrating keratoplasties performed with corneas stored in MK versus OC, no significant differences were observed in visual acuity, endothelial cell density, and cell loss. The observed thinner grafts after OC compared with MK could not be explained.

Effect of oral acyclovir after penetrating keratoplasty for herpetic keratitis: a placebo-controlled multicenter trial.

OBJECTIVE: To determine the prophylactic effect of oral acyclovir on the recurrence rate of herpetic eye disease after penetrating keratoplasty. DESIGN: A randomized, double-masked, placebo-controlled multicenter trial. PARTICIPANTS: Sixty-eight consecutive patients (68 eyes) with corneal opacities due to herpetic eye disease who underwent penetrating keratoplasty. INTERVENTION: Oral acyclovir 400 mg twice daily or placebo tablets for 6 months. MAIN OUTCOME MEASURES: The recurrence rate of herpetic eye disease-related events and rejection episodes, proven by viral cell culture or polymerase chain reaction. RESULTS: During the 2-year follow-up period, there were 3 culture-proven herpetic eye disease recurrences in the acyclovir group and 9 in the placebo group. Lifetime survival analysis of the probability of remaining free from recurrence revealed a significantly reduced risk of recurrent herpetic disease in the acyclovir-treated group. CONCLUSION: This study suggests that oral acyclovir effectively prevents herpes-related recurrences after penetrating keratoplasty in herpetic eye disease.