Cost-Effectiveness of Antifungal Supplementation of Corneal Cold Storage Media.

PURPOSE: To evaluate the cost-effectiveness of supplementing hypothermic cold storage media (CSM) with antifungal therapy. DESIGN: Cost-effectiveness analysis (CEA). PARTICIPANT: Base case of a patient with Fuch's endothelial dystrophy undergoing a first eye keratoplasty. METHODS: Cost-effective analysis of the base case with corneal tissue stored in CSM or CSM supplemented with antifungal therapy over a 16-year time horizon. Multiple clinical scenarios were considered, including endothelial keratoplasty (EK) and penetrating keratoplasty (PK); amphotericin B, voriconazole, caspofungin, and combination therapy; and third-party payer and societal perspectives. The incidences were derived from PubMed literature searches and average wholesale prices of medications; all costs were discounted 3% per annum and adjusted for inflation to 2019 US dollars. MAIN OUTCOME MEASURES: Incremental cost-effectiveness ratios (ICERs). RESULTS: In the reference case, a corneal endothelial graft stored in amphotericin B-supplemented CSM was the most cost-effective approach from a third-party payer and societal perspective. Probability sensitivity analysis (PSA) of the societal model for the EK was robust, with 93.5% being below an arbitrary willingness-to-pay threshold (WTP) of $20 000 per fungal infection averted. Voriconazole, caspofungin, and combination antifungals were less cost-effective than amphotericin B. The main factors influencing the CEA were the incidences of postkeratoplasty fungal infections, potential increases in graft failures, and antifungal costs. For grafts intended for PKs, antifungal supplementation was less cost-effective than for EKs. CONCLUSIONS: Antifungal supplementation with amphotericin B for EK grafts was the most cost-effective approach of the studied antifungals; however, the CEA was sensitive to potential changes in graft failure rates, underlining the importance of long-term safety studies. For full-thickness corneal grafts, antifungal supplementation was less cost-effective.

Corneal Collagen Cross-Linking in the Management of Keratoconus in Canada: A Cost-Effectiveness Analysis.

PURPOSE: To use patient-level microsimulation models to evaluate the comparative cost-effectiveness of early corneal cross-linking (CXL) and conventional management with penetrating keratoplasty (PKP) when indicated in managing keratoconus in Canada. DESIGN: Cost-utility analysis using individual-based, state-transition microsimulation models. PARTICIPANTS: Simulated cohorts of 100 000 individuals with keratoconus who entered each treatment arm at 25 years of age. Fellow eyes were modeled separately. Simulated individuals lived up to a maximum of 110 years. METHODS: We developed 2 state-transition microsimulation models to reflect the natural history of keratoconus progression and the impact of conventional management with PKP versus CXL. We collected data from the published literature to inform model parameters. We used realistic parameters that maximized the potential costs and complications of CXL, while minimizing those associated with PKP. In each treatment arm, we allowed simulated individuals to move through health states in monthly cycles from diagnosis until death. MAIN OUTCOME MEASURES: For each treatment strategy, we calculated the total cost and number of quality-adjusted life years (QALYs) gained. Costs were measured in Canadian dollars. Costs and QALYs were discounted at 5%, converting future costs and QALYs into present values. We used an incremental cost-effectiveness ratio (ICER = difference in lifetime costs/difference in lifetime health outcomes) to compare the cost-effectiveness of CXL versus conventional management with PKP. RESULTS: Lifetime costs and QALYs for CXL were estimated to be Can$5530 (Can$4512, discounted) and 50.12 QALYs (16.42 QALYs, discounted). Lifetime costs and QALYs for conventional management with PKP were Can$2675 (Can$1508, discounted) and 48.93 QALYs (16.09 QALYs, discounted). The discounted ICER comparing CXL to conventional management was Can$9090/QALY gained. Sensitivity analyses revealed that in general, parameter variations did not influence the cost-effectiveness of CXL. CONCLUSIONS: CXL is cost-effective compared with conventional management with PKP in the treatment of keratoconus. Our ICER of Can$9090/QALY falls well below the range of Can$20 000 to Can$100 000/QALY and below US$50 000/QALY, thresholds generally used to evaluate the cost-effectiveness of health interventions in Canada and the United States. This study provides strong economic evidence for the cost-effectiveness of early CXL in keratoconus.

Fungal Keratitis: A Six-Year Review at a Tertiary Referral Centre.

Background This review reports the epidemiology, laboratory results, treatment regimens and costs of fungal keratitis at a tertiary referral center in Lucerne, Switzerland. Patients and Methods Culture-proven fungal infections between January 2010 and December 2015 were reviewed retrospectively. Results Seventeen patients with a mean age of 52 years were identified. Contact lens wear was the most important risk factor (n = 11) (65 % of all cases), with filamentous fungi being identified as the most common fungus type (n = 10) (91 % of all cases of contact lens-associated fungal keratitis). All non-contact lens-associated fungal infections (n = 6) (35 % of all cases) were related to Candida spp. Six patients (35 %) were treated on an outpatient basis; 11 cases (65 %) required hospitalisation. Systemic voriconazole was the treatment regimen prescribed most often (n = 12) (71 %), followed by topical natamycin 5 % (n = 11) (65 %). Corneal crosslinking and penetrating keratoplasty were required in 4 cases each (24 %). One case ended up in enucleation (6 %). Average costs per case were EUR 15 952 for hospitalised patients if surgical intervention was required, and EUR 7415 if no intervention was performed. Average costs for outpatients were EUR 7079. In a majority of cases, visual acuity could be improved (n = 9) (53 %) or preserved (n = 2) (12 %). Conclusion Despite the relatively low incidence of culture-proven keratitis (17 cases in 6 years), a clear pattern with regard to risk factors and fungus species was noted. In the absence of a gold standard for the treatment of fungal keratitis, the combination of systemic voriconazole and topical natamycin seems to be one of the most commonly used antifungal treatment regimens. The costs of outpatient versus inpatient non-surgical treatment were approximately the same.

Racial/Ethnic Differences in Rates of Penetrating or Endothelial Keratoplasty for Fuchs Endothelial Corneal Dystrophy Among US Medicare Beneficiaries.

IMPORTANCE: Fuchs endothelial corneal dystrophy (FECD) is the most common indication for corneal transplant in the United States. The association between race/ethnicity and incidence of advanced FECD, defined by a need for endothelial or penetrating keratoplasty, has not been investigated. OBSERVATIONS: The 2014 US Medicare Limited Data Set (5% sample of 27 163 740 fee-for-service Medicare patients) was analyzed for rate of keratoplasty performed for FECD (International Classification of Diseases, Ninth Edition code 371.57), stratified by race/ethnicity. Among all Medicare beneficiaries 65 years or older, a diagnosis code for FECD was used in 1.55% (95% CI, 1.51%-1.59%) of white and 1.38% (95% CI, 1.26%-1.50%) of African American beneficiaries who had an ophthalmologist eye examination in 2014 (P = .01). Among beneficiaries who obtained medical care for FECD, keratoplasty was 1.9 times more likely in white than African American patients (4.7%; 95% CI, 4.2%-5.2% vs 2.5%; 95% CI, 1.1%-3.9%; P < .001) among approximately 6500 patients undergoing 8420 procedures. CONCLUSIONS AND RELEVANCE: In 2014, keratoplasty was 1.9 times more likely in US Medicare fee-for-service white patients than African American patients with FECD. This might be caused by racial/ethnic differences in the biology of FECD, access to care, or other unidentified factors.

Comparative cost-effectiveness analysis of descemet stripping automated endothelial keratoplasty versus penetrating keratoplasty in the United States.

PURPOSE: To perform a comparative cost-effectiveness analysis of Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK) for corneal endothelial disease. DESIGN: Retrospective cost-effectiveness analysis. METHODS: This cost-effectiveness analysis was performed from a third-party payer perspective with a 5-year time horizon. Probabilities of outcomes and complications of each of the procedures were calculated based on review of the published literature. A model was constructed to compare the costs and utilities associated with DSAEK and PK. Costs of donor tissue preparation, surgery, follow-up, postoperative complications, and procedures were considered. Utility values were based on quality-adjusted life years associated with visual acuity outcomes. Both costs and utilities were discounted at 3% per year. Sensitivity analyses were performed on key model inputs. RESULTS: Base case analysis found DSAEK to be less costly compared with PK ($9362 vs $10 239), with greater utility (3.15 vs 2.47 quality-adjusted life years). Sensitivity analyses revealed that even at graft failure rates for DSAEK approaching the rates for PK, DSAEK would still reduce costs. Varying the dislocation rate in our model showed that even at dislocation rates approaching 50%, DSAEK remained less costly. Further, with DSAEK rejection rates as high as 28%, DSAEK would remain a dominant procedure over PK. CONCLUSIONS: Comparative cost-effectiveness analysis of DSAEK versus PK indicates favorable cost and utility outcomes associated with DSAEK for treatment of corneal endothelial disease. Longer follow-up of DSAEK outcomes will provide more accurate information regarding long-term cost-effectiveness of the procedure.

Cost-effectiveness of Descemet's stripping endothelial keratoplasty versus penetrating keratoplasty.

PURPOSE: Selective endothelial transplantation in the form of Descemet's stripping endothelial keratoplasty (DSEK) is rapidly replacing traditional full-thickness penetrating keratoplasty (PK) for endothelial disease. An incremental cost-effectiveness analysis was performed to determine whether the benefits of DSEK are worth the additional costs. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients at the Singapore National Eye Center, a tertiary eye center in Singapore, with Fuchs' dystrophy or bullous keratopathy who underwent either PK or DSEK. INTERVENTION: Patients underwent either PK (n = 171) or DSEK (n = 93) from January 2001 through December 2007. Data were collected from inpatient and outpatient notes corresponding to the time immediately before the procedure to up to 3 years after. MAIN OUTCOME MEASURES: Improvements in best spectacle-corrected visual acuity were used to calculate the increase in quality-adjusted life years (QALYs) 3 years after the procedure. This was combined with hospital charges (a proxy for costs) to determine incremental cost-effectiveness ratios (ICERs) comparing PK with no intervention and DSEK with PK. RESULTS: Three-year charges for DSEK and PK were $7476 and $7236, respectively. The regression-adjusted improvement in visual acuity for PK relative to no intervention was -0.613 logarithm of the minimum angle of resolution (logMAR) units (P<0.001), and for DSEK relative to PK, it was -0.199 logMAR units (P = 0.045). The regression-adjusted marginal gain in utility for PK relative to no intervention was 0.128 QALYs (P<0.001) and for DSEK relative to PK was 0.046 QALYs (P = 0.031). This resulted in ICERs of $56 409 per QALY for PK relative to no intervention and $5209 per QALY for the more expensive DSEK relative to PK. CONCLUSIONS: If the goal is to maximize societal health gains given fixed resources, DSEK should be the preferred strategy. For a fixed budget, it is possible to achieve greater QALY gains by providing DSEK to as many patients as possible (and nothing to others), rather than providing PK.

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.

Incremental cost-utility analysis of deep anterior lamellar keratoplasty compared with penetrating keratoplasty for the treatment of keratoconus.

PURPOSE: This study sought to determine the cost effectiveness of deep anterior lamellar keratoplasty (DALK) compared with penetrating keratoplasty (PK) for the treatment of keratoconus. DALK is associated with lower rates of postoperative complications compared with PK, but is a more expensive procedure; whether it is cost effective compared with PK is unknown. DESIGN: The study was an incremental cost-utility analysis from a health systems perspective using retrospective data on a cohort of patients with severe keratoconus. METHODS: The analysis was conducted using 1-year cost and outcomes data from 148 keratoconus patients, representing 102 PK and 46 DALK cases, seen for corneal grafts between January 1991 and January 2009 at the Singapore National Eye Center. The main outcome assessed was the incremental cost-utility ratios associated with PK and DALK for the treatment of keratoconus. RESULTS: Over a 20-year period, PK was the lower cost procedure and had an incremental cost-utility ratio of $3,750 per quality-adjusted life-year compared with no surgical treatment. Compared with PK, DALK has an incremental quality-adjusted life-year gain of 0.8 and an incremental cost of $2,420, for an incremental cost-utility ratio of $3,025 per quality-adjusted life-year. CONCLUSIONS: Compared with PK, DALK has a favorable cost-effectiveness ratio and, resources permitting, should be considered as a first-line treatment for keratoconus. Additional studies are needed to confirm the expected advantages of DALK over PK when it comes to long-term graft failure rates.

The lifetime economic burden of keratoconus: a decision analysis using a markov model.

PURPOSE: To estimate the expected incremental lifetime cost of treatment of keratoconus compared to the expected cost of the treatment of myopia. DESIGN: Cost estimate from the patient's perspective using a Markov decision model. METHODS: We modeled a hypothetical cohort of people with clinically significant incident keratoconus as defined by the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. We included costs of clinic visits, fitting fees, contact lenses, surgical procedures, and complications. Survival curves of corneal transplants and associated complications were modeled using data from the 2007 Australian Graft Registry. Medical treatment regimens after surgery were defined by expert opinion. RESULTS: The expected value of the lifetime cost of the treatment of keratoconus over myopia was $25 168 with a standard deviation of $16 247 and a median of $17 596. The factors that most influenced the lifetime cost were the probability of initial corneal transplant and a subsequent regraft. The cost of routine care had relatively little influence on the lifetime cost of care. CONCLUSIONS: The expected lifetime cost of treatment of keratoconus represents a significant cost to patients and payors. While the cost of routine care for keratoconus is not trivial, the primary factor influencing changes in the cost of care for keratoconus is the probability of corneal transplant. Combined with the significantly impaired vision-related quality of life and the relatively young onset of disease, the economic burden of the treatment of keratoconus represents a significant public health concern.

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.

Economic impact of the advent of posterior lamellar keratoplasty in Montreal, Quebec.

OBJECTIVE: To assess the cost-utility of posterior lamellar keratoplasty (PLK) techniques, including deep lamellar endothelial keratoplasty, Descemet stripping endothelial keratoplasty, and Descemet stripping automated endothelial keratoplasty, in the treatment of corneal endothelial diseases. DESIGN: Cost-utility analysis based on a Markov model. PARTICIPANTS: Cohort of 100 patients waiting for corneal graft. METHODS: This cost-utility analysis was performed from a Canadian health system perspective over a lifetime period. A Markov model was constructed to compare the cost per quality-adjusted life-year (QALY) associated with penetrating keratoplasty (PK) and PLK techniques. The model included all major health states relevant to patients scheduled for corneal transplant: waiting for transplant, surviving graft with or without complications, irreversible failure, noneligibility, and death. Transition probabilities among health states were obtained from published clinical trials. Costs considered were those associated with surgery, patients' follow-up, and postsurgical complications. Number of QALYs was estimated presurgery and postsurgery using the Brown and Sharma conversion chart. RESULTS: PLK proved to be more effective, providing more QALYs (+13 QALYs/100 patients), and it was less costly (-$68,792/100 patients) compared with PK. Deterministic and probabilistic sensitivity analyses confirmed the robustness of the base-case results. CONCLUSIONS: From a clinical and an economic standpoint, PLK in the management of patients waiting for corneal graft represents a preferred strategy compared with PK only.

The value-based medicine comparative effectiveness and cost-effectiveness of penetrating keratoplasty for keratoconus.

OBJECTIVE: To perform a base case, comparative effectiveness, and cost-effectiveness (cost-utility) analysis of penetrating keratoplasty for patients with severe keratoconus. METHODS: Visual acuity data were obtained from a large, retrospective multicenter study in which patients with keratoconus with less than 20/40 best corrected visual acuity and/or the inability to wear contact lenses underwent penetrating keratoplasty, with an average follow-up of 2.1 years. The results were combined with other retrospective studies investigating complication rates of penetrating keratoplasty. The data were then incorporated into a cost-utility model using patient preference-based, time trade-off utilities, computer-based decision analysis, and a net present value model to account for the time value of outcomes and money. The comparative effectiveness of the intervention is expressed in quality-of-life gain and QALYs (quality-adjusted life-years), and the cost-effectiveness results are expressed in the outcome of $/QALY (dollars spent per QALY). RESULTS: Penetrating keratoplasty in 1 eye for patients with severe keratoconus results in a comparative effectiveness (value gain) of 16.5% improvement in quality of life every day over the 44-year life expectancy of the average patient with severe keratoconus. Discounting the total value gain of 5.36 QALYs at a 3% annual discount rate yields 3.05 QALYs gained. The incremental cost for penetrating keratoplasty, including all complications, is $5934 ($5913 discounted at 3% per year). Thus, the incremental cost-utility (discounted at 3% annually) for this intervention is $5913/3.05 QALYs = $1942/QALY. If both eyes undergo corneal transplant, the total discounted value gain is 30% and the overall cost-utility is $2003. Surgery on the second eye confers a total discounted value gain of 2.5 QALYs, yielding a quality-of-life gain of 11.6% and a discounted cost-utility of $2238/QALY. CONCLUSIONS: Penetrating keratoplasty for patients with severe keratoconus seems to be a comparatively effective and cost-effective procedure when compared with other interventions across different medical specialties.

Cost utility for penetrating keratoplasty in patients with poor binocular vision.

PURPOSE: Cost-utility and cost-effectiveness analyses are of increasing importance to clinicians and health policy experts. This study determines the costs in Germany and other countries in relation to gain of utility for patients with bilateral poor vision owing to corneal disease undergoing penetrating keratoplasty (PK) in 1 eye. DESIGN: A cost-utility analysis was performed using retrospective clinical data and high-level evidence-based data. PARTICIPANTS: Sixty patients (mean age, 46.3 years) with bilateral poor vision who underwent PK for corneal disease. METHODS: Visual acuity and utility values were obtained before and 1 year after PK and after suture removal. A 10-year graft survival rate of 80% was assumed. Expenses included costs for the corneal transplant and surgery, medication, and optical rehabilitation. A discount rate of 5% was applied for costs and quality-adjusted life years (QALYs). Cost-utility analysis encompassed a 10-year period after surgery. MAIN OUTCOME MEASURES: The number of QALYs was calculated for the study group undergoing PK. This was divided into the cost of the procedure to get the number of euros spent per QALY gained. RESULTS: Median binocular preoperative visual acuity was -log mean angle of resolution (-logMAR) 0.91+/-0.53 (Snellen equivalent 20/160) yielding a utility value of 0.67. After suture removal and optical rehabilitation, binocular visual acuity increased to median -logMAR 0.36+/-0.36 (20/46) with a utility value of 0.79. Over the 10 years after surgery and considering graft survival and discounting, a cost utility of 9551 euros per QALY was gained (equivalent to US11,557 dollars). One-way sensitivity analysis yielded a range from 7706 euros to 12874 euros per QALY, highlighting the robustness of the model. CONCLUSIONS: Although an expensive procedure, PK is cost effective in patients with bilateral poor vision.