Cost effectiveness of collagen crosslinking for progressive keratoconus in the UK NHS.
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ABSTRACT: Background
Keratoconus is a progressive degenerative corneal disorder of children and young adults that is traditionally managed by refractive error correction, with corneal transplantation reserved for the most severe cases. UVA collagen crosslinking is a novel procedure that aims to prevent disease progression, currently being considered for use in the UK NHS. We assess whether it might be a cost-effective alternative to standard management for patients with progressive keratoconus.Methods
We constructed a Markov model in which we estimated disease progression from prospective follow-up studies, derived costs derived from the NHS National Tariff, and calculated utilities from linear regression models of visual acuity in the better-seeing eye. We performed deterministic and probabilistic sensitivity analyses to assess the impact of possible variations in the model parameters.Results
Collagen crosslinking is cost effective compared with standard management at an incremental cost of £ 3174 per QALY in the base case. Deterministic sensitivity analysis shows that this could rise above £ 33,263 per QALY if the duration of treatment efficacy is limited to 5 years. Other model parameters are not decision significant. Collagen crosslinking is cost effective in 85% of simulations at a willingness-to-pay threshold of £ 30,000 per QALY.Conclusion
UVA collagen crosslinking is very likely to be cost effective, compared with standard management, for the treatment of progressive keratoconus. However, further research to explore its efficacy beyond 5 years is desirable.
SUBMITTER: Salmon HA
PROVIDER: S-EPMC4645452 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We compared one-year outcomes of conventional (3 mW/cm(2), 365-nm ultraviolet-A light, 30 minutes) and accelerated (18 mW/cm(2), 365-nm ultraviolet-A light, 5 minutes) collagen crosslinking (CXL) in patients with progressive keratoconus. Main outcome measures were change in keratometry, uncorrected visual acuity (UCVA), and best-corrected visual acuity (BCVA). Nineteen patients in each group completed 1-year follow-up. Preoperatively, there were no inter-group differences for age, keratometry, corneal thickness, and spherical equivalent (p > 0.127). One year postoperatively, maximum and minimum keratometry were flattened by 1.6 diopters (p < 0.023) and 2 diopters (p < 0.047) respectively after conventional CXL, and, 0.47 diopters (p = 0.471) and 0.19 diopters (p = 0.120) respectively after accelerated CXL. Association analysis showed significant negative association between baseline maximum keratometry and change in maximum keratometry after accelerated CXL (p = 0.002) but not after conventional CXL (p = 0.110). Corneal thickness was reduced significantly in both groups (p = 0.017). An improvement in UCVA (p < 0.001) and BCVA (p < 0.022) was noted in both groups along with a reduction in spherical equivalent postoperatively (p < 0.026). There were no inter-group differences for any of the parameters postoperatively (p > 0.184). Although no statistically significant differences were observed between both treatment modalities, a more effective topographic flattening was observed with conventional CXL as compared to accelerated CXL in this study.
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Project description:The purpose of this study was to evaluate the safety and efficacy of transepithelial corneal collagen cross linking (TE-CXL) with modified riboflavin and accelerated UVA irradiance in thin corneas with pachymetry less than 400 microns at thinnest point, untreatable by epithelium off corneal collagen cross linking (CXL) in adult Pakistani population with progressive keratoconus.This quasi experimental study included twenty six eyes of 26 patients with progressive keratoconus who underwent accelerated transepithelial CXL in Armed forced institute of ophthalmology with 12 months follow up. Modified riboflavin, ParaCel ((riboflavin 0.25%, Benzalkonium chloride, EDTA, Trometamol, hydroxypropyl methylcellulose) and vibeX Xtra (riboflavin 0.25%) (Avedro, USA)) were applied to cornea in two stages. Uncorrected and Corrected Distant Visual Acuities (UDVA, CDVA), spherical equivalent (SE), astigmatism, pachymetry at thinnest point (Pachy thin), apex keratometry (Kmax), simulated and steep keratometry (Sim K, steep K) were measured at baseline and at 3, 6 and 12 months post operatively. The cornea was then exposed to accelerated UVA irradiance of 9mW/cm2 for 10 min (total dose 30 mW/cm2).The mean age of the patient was 24.54±5.16 years. UDVA, CDVA, SE, astigmatism significantly improved at all postoperative test points (p=0.000, 0.004, 0.000, 0.004 respectively). Kmax and pachy thin were significantly reduced over baseline at 1 year (p=0.000, 0.004 respectively). Topographic indices Sim K and steep K did not show significant changes. No intra or post-operative complications were reported.Transepithelial accelerated CXL with modified riboflavin is a safe and effective procedure which halt disease progression in thin corneas with progressive keratoconus.
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Project description:This review aims to assess the efficacy and safety of epithelial removal (ER) and transepithelial (TE) corneal collagen crosslinking (CXL) for the treatment of keratoconus. We used MEDLINE to identify all ER and TE CXL studies on keratoconic eyes (n≥20, follow-up ≥12 months). Ex vivo and studies for non-keratoconus indications or in conjunction with other procedures were excluded. Data on uncorrected (UDVA) and corrected (CDVA) distance visual acuity, refractive cylinder, maximum keratometry (Kmax), and adverse events were collected at the latest follow-up and 1 year. Only one randomised controlled trial (RCT) qualified inclusion. Forty-four ER and five TE studies were included. For logMAR UDVA, CDVA, mean spherical equivalent, refractive cylinder and Kmax, at latest follow-up 81, 85, 93, 62, and 93% ER studies vs 66.7, 80, 75, 33, and 40% TE studies reported improvement, respectively. Whereas at 1 year, 90, 59, and 91% ER studies vs 80, 50, and 25% TE studies reported improvement, respectively. The majority of studies showed reduced pachymetry in both groups. Treatment failure, retreatment rates, and conversion to transplantation were reported to be up to 33, 8.6, and 6.25%, respectively, in ER studies only. Stromal oedema, haze, keratitis, and scarring were only reported in ER studies, whereas endothelial cell counts remained variable in both groups. Both ER and TE studies showed improvement in visual acuity, refractive cylinder but Kmax worsened in most TE studies. Adverse events were reported more with ER studies. This review calls for more high quality ER and TE studies with comparable parameters for further assessment of safety and efficacy.
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Project description:PurposeTo evaluate clinical practice in the diagnosis and treatment of progressive keratoconus with corneal crosslinking (CXL) in four Nordic countries.MethodsA questionnaire was sent to all centres at which keratoconus patients are evaluated and CXL is performed in Sweden, Denmark, Norway and Iceland. Nineteen of 20 centres participated.ResultsCXL is performed approximately 1300 times per year in these four Nordic countries with a population of around 21.7 million (2019). In most cases, progression is evaluated using the Pentacam HR, and the maximum keratometry reading (Kmax ) is considered the most important parameter. The most frequently used treatment protocol in Scandinavia is the 9 mW/cm2 epi-off protocol, using hydroxylpropyl methylcellulose riboflavin (HPMC-riboflavin). The participants deemed the following areas to be in most need of improvement: adaptation of the CXL protocol to individual patients (5/19), the development of effective epi-on treatment protocols (4/19), optimal performance of CXL in thin corneas (4/19), improvement of the definition of progression (2/19), and diagnosis of the need for re-treatment (2/19).ConclusionsWe concluded that the diagnosis of progressive keratoconus and the diagnostic equipment used are similar. Treatment strategies are also similar but are suitably different to provide an interesting basis for the comparison of treatment outcomes. The high degree of participation in this survey indicates the possibility of future scientific collaboration on CXL focusing on the areas deemed to need improvement. It would also be of interest to evaluate the possibility of creating a Nordic CXL Registry. The high number of CXL treatments performed ensures sufficient statistical power to solve many questions. Such a registry could be an important contribution to evidence-based care and would allow for longitudinal evaluation.
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Project description:Corneal collagen crosslinking with riboflavin photosensitization and ultraviolet irradiation is a novel approach to limiting the progression of keratoconus in patients by increasing the elastic modulus of the degenerate cornea. Beneficial reductions in corneal steepness and aberrations after crosslinking also frequently occur. In a previous study, we described a computational modeling approach to simulating topographic progression in keratoconus and regression of disease with corneal collagen crosslinking. In the current study, this model has been expanded and applied to the inverse problem of estimating longitudinal time-dependent changes in the corneal elastic modulus after crosslinking using in vivo measurements from 16 human eyes. Topography measured before crosslinking was used to construct a patient-specific finite element model with assumed hyperelastic properties. Then the properties of the cornea were altered using an inverse optimization method to minimize the difference between the model-predicted and in vivo corneal shape after crosslinking. Effects of assumptions regarding sclera-to-cornea elastic modulus ratio and spatial attenuation of treatment effect due to ultraviolet beam characteristics on the predicted change in elastic modulus were also investigated. Corneal property changes computed by inverse finite element analysis provided excellent geometric agreement with clinical topography measurements in patient eyes post-crosslinking. Over all post-treatment time points, the estimated increase in corneal elastic modulus was 110.8 ± 48.1%, and slightly less stiffening was required to produce the same amount of corneal topographic regression of disease when the sclera-to-cornea modulus ratio was increased. Including the effect of beam attenuation resulted in greater estimates of stiffening in the anterior cornea. Corneal shape responses to crosslinking varied considerably and emphasize the importance of a patient-specific approach.
| S-EPMC4104483 | biostudies-literature
Project description:IntroductionEpithelium-off cross-linking (epi-off CXL) has long been established as the gold standard treatment for progressive keratoconus. Several protocols for epithelium-on (epi-on) CXL have been proposed to help reduce post-operative pain and facilitate visual recovery, but there is no epi-on treatment approach that is currently approved in the United States. The hydrophilic and macromolecular characteristics of conventional epi-off riboflavin formulations may create clinical challenges for absorption through an intact epithelium. This study investigates the clinical efficacy of a dextran-free hypotonic riboflavin ophthalmic solution (Photrexa, Glaukos, Burlington, MA, USA), approved for epi-off CXL, in a novel epi-on CXL protocol.MethodsTwenty-five eyes of 17 patients were treated in this prospective, single-arm study using a hypotonic riboflavin formulation without dextran and low irradiance UVA (3mW/cm2) for epi-on CXL. Visual acuity, as well as refractive and keratometry outcomes, were observed over 12 months.ResultsAt 12 months, Kmax was stable with no clinically or statistically significant change from a mean pre-op of 55.4D to 55.9D (p=0.13). Uncorrected and best corrected logMAR visual acuity significantly improved from 0.77 to 0.62 and from 0.17 to 0.12, respectively. There were no significant adverse safety events.ConclusionPatients who underwent epi-on CXL with dextran-free hypotonic riboflavin demonstrated improvements in uncorrected and best corrected visual acuity with stable keratometry at 12 months post-operatively. The efficacy is consistent with other epi-on studies to date but remains lower than standard epi-off CXL. New technologies, including supplemental oxygen and transepithelial riboflavin ophthalmic solutions, are currently under clinical evaluation and may offer a path forward for epi-on CXL in the USA.
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Project description:ObjectiveTo assess the overall cost effectiveness of the NHS breast screening programme, based on findings of the Independent UK Panel on Breast Cancer Screening and taking into account the uncertainty of associated estimates of benefits, harms, and costs.DesignA life table model comparing data from two cohorts.SettingUnited Kingdom's health service.Participants and interventions364,500 women aged 50 years-the population of 50 year old women in England and Wales who would be eligible for screening-were followed up for 35 years without screening, compared with a similar cohort who had regular mammographic screening between ages 50 and 70 years and were then followed for another 15 years.Main outcome measuresBetween the cohorts, we compared the number of breast cancer diagnoses, number of deaths from breast cancer, number of deaths from other causes, person years of survival adjusted for health quality, and person years of survival with breast cancer. We also calculated the costs of treating primary and end stage breast cancer, and the costs of screening. Probabilistic sensitivity analysis explored the effect of uncertainty in key input parameters on the model outputs.ResultsUnder the base case scenario (using input parameters derived from the Independent Panel Review), there were 1521 fewer deaths from breast cancer and 2722 overdiagnosed breast cancers. Discounting future costs and benefits at a rate of 3.5% resulted in an additional 6907 person years of survival in the screened cohort, at a cost of 40,946 additional years of survival after a diagnosis of breast cancer. Screening was associated with 2040 additional quality adjusted life years (QALYs) at an additional cost of £42.5m (€49.8m; $64.7m) in total or £20,800 per QALY gained. The gain in person time survival over 35 years was 9.2 days per person and 2.7 quality adjusted days per person screened. Probabilistic sensitivity analysis showed that this incremental cost effectiveness ratio varied widely across a range of plausible scenarios. Screening was cost effective at a threshold of £20,000 per QALY gained in 2260 (45%) scenarios, but in 588 (12%) scenarios, screening was associated with a reduction in QALYs.ConclusionThe NHS breast screening programme is only moderately likely to be cost effective at a standard threshold. However, there is substantial uncertainty in the model parameter estimates, and further primary research will be needed for cost effectiveness studies to provide definitive data to inform policy.
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Project description:PurposeThe aim of this study was to assess changes in visual acuity after epithelium-on ("epi-on") corneal crosslinking after a diagnosis of keratoconus.MethodsSubjects with corneal ectatic diseases were enrolled in a prospective, randomized, controlled, open-label, multicenter trial. Subjects were randomized to 1 of 3 treatment groups and treated with an epi-on crosslinking system including riboflavin/sodium iodide and pulsed UVA exposure (EpiSmart, CXL Ophthalmics, Encinitas, CA). The UVA treatment groups were 2.4 J/cm 2 over 20 minutes, 3.6 J/cm 2 over 20 minutes, and 3.6 J/cm 2 over 30 minutes. The primary end point was logarithm of the minimum angle of resolution corrected distance visual acuity (CDVA). Secondary end points were logarithm of the minimum angle of resolution uncorrected distance visual acuity (UCVA), maximum corneal curvature (Kmax), and minimum corneal thickness. Data were assessed 6 and 12 months post-operatively, using t -tests for differences from baseline.ResultsTwo thousand two hundred twenty-eight subjects were treated with epi-on crosslinking. One thousand nine hundred twenty-two subjects had a diagnosis of keratoconus; other treated eyes had postsurgical and other ectasias. At 6 and 12 months, the subjects with keratoconus demonstrated significant improvements in CDVA, UCVA, and Kmax; minimum corneal thickness was unchanged. One hundred ninety-five subjects (8.7%) reported at least 1 adverse event (AE). A mild corneal epithelial defect was reported in 31 cases (1.4%) and was the only AE reported in >1% of subjects. There were no serious AEs related to the treatment.ConclusionsEpiSmart epi-on crosslinking resulted in mean improvements in CDVA, UCVA, and Kmax at both 6 and 12 months and an excellent safety and efficacy profile in subjects with keratoconus, with few significant side effects. Differences between UVA treatment groups were not significant.
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