Burden of Infantile Hemangioma on Family: An International Observational Cross-Sectional Study.

BACKGROUND/OBJECTIVES: Infantile hemangioma (IH) is the most frequent benign tumor of infancy resulting from vascular proliferation. Data regarding the burden on families of children with IHs are limited. This study aimed to characterize IHs and provide a comprehensive evaluation of the burden of IHs on parents of children requiring systemic treatment in the United States and Europe. METHODS: This noninterventional cross-sectional study included infants with newly diagnosed IH requiring systemic treatment. A parent or family member completed two questionnaires (Family Member questionnaire; Hemangioma Family Burden [HFB] questionnaire). RESULTS: A total of 693 individuals were evaluable in five countries. IHs were observed in more girls than boys (66%-83% female) and the mean age at inclusion was 0.44 to 1.4 years. Approximately half of patients had superficial IHs, approximately 70% of cases affected the head, and approximately 80% of cases were moderate or severe. Most patients received propranolol treatment. Their child's IH affected more than 70% of parents in each country, but fewer than 10% were offered psychological support. Approximately half of all parents reported that their child's IH affected their professional life. The global HFB score was significantly (p < 0.001) greater with greater IH severity. More than 90% of parents in each country were satisfied with the care of their child's disease. CONCLUSIONS: This international study using the validated HFB questionnaire provides further insight into the burden of IH and highlights potential areas for future focus in assisting families with affected children.

Protoporphyrin retention in hepatocytes and Kupffer cells prevents sclerosing cholangitis in erythropoietic protoporphyria mouse model.

BACKGROUND & AIMS: Chronic, progressive hepatobiliary disease is the most severe complication of erythropoietic protoporphyria (EPP) and can require liver transplantation, although the mechanisms that lead to liver failure are unknown. We characterized protoporphyrin-IX (PPIX)-linked hepatobiliary disease in BALB/c and C57BL/6 (Fechm1Pas) mice with mutations in ferrochelatase as models for EPP. METHODS: Fechm1Pas and wild-type (control) mice were studied at 12-14 weeks of age. PPIX was quantified; its distribution in the liver, serum levels of lipoprotein-X, liver histology, contents of bile salt and cholesterol phospholipids, and expression of genes were compared in mice of the BALB/c and C57BL/6 backgrounds. The in vitro binding affinity of PPIX for bile components was determined. RESULTS: Compared with mice of the C57BL/6 background, BALB/c Fechm1Pas mice had a more severe pattern of cholestasis, fibrosis with portoportal bridging, bile acid regurgitation, sclerosing cholangitis, and hepatolithiasis. In C57BL/6 Fechm1Pas mice, PPIX was sequestrated mainly in the cytosol of hepatocytes and Kupffer cells, whereas, in BALB/c Fechm1Pas mice, PPIX was localized within enlarged bile canaliculi. Livers of C57BL/6 Fechm1Pas mice were protected through a combination of lower efflux of PPIX and reduced synthesis and export of bile acid. CONCLUSIONS: PPIX binds to bile components and disrupts the physiologic equilibrium of phospholipids, bile acids, and cholesterol in bile. This process might be involved in pathogenesis of sclerosing cholangitis from EPP; a better understanding might improve diagnosis and development of reagents to treat or prevent liver failure in patients with EPP.

Contribution of modeling approaches and virtual populations in transposing the results of clinical trials into real life and in enlightening public health decisions.

Modeling consists in aggregating separate pieces of knowledge, according to a given structure and rules. It allows studying the behavior of more or less complex systems by simulation techniques. Modeling is used in different state-of-the-art technological domains (meteorology, aeronautics). Its use has grown for the evaluation of medicines and medical devices, from conception to prescription (marketing authorization, reimbursement, price setting and re-registrations). It follows a scientific approach and is the object of good practice recommendations. Coupling models to virtual populations allows obtaining realistic results at the population level, testing diagnostic or therapeutic strategies, as well as estimating the consequences of transposing the results of clinical trials to the population. Through examples, the participants of the Round Table analyzed the contributions of the coupling of models and realistic virtual populations, and proposed guidelines for their judicious and systematic use.

Metric properties of the MacDQoL, individualized macular-disease-specific quality of life instrument, and newly identified subscales in French, German, Italian, and American populations.

OBJECTIVES: The aims of this analysis were to confirm the UK results in other countries and to explore the possibility of subscales of the 25-Item Macular disease Dependent Quality of Life (MacDQoL) questionnaire. METHODS: Two clinical studies were pooled. Principal components analyses (Varimax) were conducted on baseline data from each country and from all combined. Factorial structures were compared between countries, and Cronbach alpha values were used to identify item clusters. Four groups of patients were created according to visual acuity (VA) in the best eye (BE < 10/20; BE ≥ 10/20) and worst eye (WE < 10/100; WE ≥ 10/100). These groups were used to investigate (analysis of variance) the sensitivity of MacDQoL to VA impairment and to compare it with the NEI-VFQ-25 generic visual function questionnaire. RESULTS: A total of 797 patients (mean age 76.8 years; 55.8% women) had wet age-related macular degeneration (AMD). Strong correlations between the MacDQoL items (r > 0.48) and factor loadings > 0.49 on a forced one-factor analysis supported the use of an average weighted impact score. Four constructs (Cronbach alpha > 0.8) were derived, represented by the labels: Essential tasks, Family/social life, Activities/capabilities, and Embarrassment. The structure did not differ among the four countries involved, except one item (Finance), which has been excluded. Patients with BE VA <10/20 and WE VA <10/100 produced significantly worse overall scores than those with BE VA >10/20 and WE VA >10/100 (MacDQoL P < 0.0001; NEI-VFQ-25 P < 0.0001). CONCLUSIONS: The analysis confirmed the metric properties of the MacDQoL. The MacDQoL offers a broad individualized measure of the impact of MD on quality of life.

Development of a new subjective questionnaire: the Freedom from Glasses Value Scale (FGVS).

PURPOSE: To develop a patient self-administered questionnaire assessing the added value of complete independence from spectacles (hereafter referred to as glasses) after multifocal intraocular lens (IOL) surgery. METHODS: Exploratory interviews with five cataract patients and six presbyopic patients with AcrySof ReSTOR IOLs (Alcon Laboratories Inc) implanted in both eyes for at least 6 months were conducted. The questionnaire's conceptual framework was developed after interview analysis. Based on the identified concepts, items were generated simultaneously in French and Spanish using patients' own words, and comprehension tested with six French patients; the Spanish questionnaire underwent clinician review and was further tested with four Spanish patients. French and Spanish versions were accordingly refined. The questionnaire was linguistically validated in UK English and Danish. RESULTS: Interview analysis resulted in the identification of 9 global concepts: global vision, practical constraints related to wearing glasses, impact of eye surgery on the patient's life, improvement of practical issues without glasses, improvement of psychological constraints without glasses, physical appearance/aesthetic aspect, self-image and in the eyes of others, eyesight problems left behind after surgery, and recommendation of surgery to others. The initial version of the test questionnaire contained 23 items; 2 items were deleted and changes were made after clinician review and patient testing. The final questionnaire named Freedom from Glasses Value Scale (FGVS) contained 21 items and four general additional questions. CONCLUSIONS: Beyond functional aspects, this qualitative study identified additional benefits in cataract and presbyopic patients living free of glasses after receiving multifocal IOLs. The FGVS now needs to be psychometrically validated (eg, construct validity and reliability).

Measuring benefits and patients' satisfaction when glasses are not needed after cataract and presbyopia surgery: scoring and psychometric validation of the Freedom from Glasses Value Scale (FGVS).

BACKGROUND: The purpose of this study was to reduce the number of items, create a scoring method and assess the psychometric properties of the Freedom from Glasses Value Scale (FGVS), which measures benefits of freedom from glasses perceived by cataract and presbyopic patients after multifocal intraocular lens (IOL) surgery. METHODS: The 21-item FGVS, developed simultaneously in French and Spanish, was administered by phone during an observational study to 152 French and 152 Spanish patients who had undergone cataract or presbyopia surgery at least 1 year before the study. Reduction of items and creation of the scoring method employed statistical methods (principal component analysis, multitrait analysis) and content analysis. Psychometric properties (validation of the structure, internal consistency reliability, and known-group validity) of the resulting version were assessed in the pooled population and per country. RESULTS: One item was deleted and 3 were kept but not aggregated in a dimension. The other 17 items were grouped into 2 dimensions ('global evaluation', 9 items; 'advantages', 8 items) and divided into 5 sub-dimensions, with higher scores indicating higher benefit of surgery. The structure was validated (good item convergent and discriminant validity). Internal consistency reliability was good for all dimensions and sub-dimensions (Cronbach's alphas above 0.70). The FGVS was able to discriminate between patients wearing glasses or not after surgery (higher scores for patients not wearing glasses). FGVS scores were significantly higher in Spain than France; however, the measure had similar psychometric performances in both countries. CONCLUSIONS: The FGVS is a valid and reliable instrument measuring benefits of freedom from glasses perceived by cataract and presbyopic patients after multifocal IOL surgery.

Scoring and psychometric properties of the Eye-Drop Satisfaction Questionnaire (EDSQ), an instrument to assess satisfaction and compliance with glaucoma treatment.

BACKGROUND: The objective of this study was to ascertain the scoring and assess the psychometric properties of the Eye-Drop Satisfaction Questionnaire (EDSQ), a 43-item Patient-Reported Outcome instrument developed to assess patients' satisfaction and compliance with glaucoma treatment. METHODS: The EDSQ was administered during an observational, retrospective study to 184 French patients treated for glaucoma. The hypothesized structure, including six dimensions (patient-clinician relationship; patient experience; patient-treatment interaction; apprehension; patient knowledge; travel), was tested by assessing the internal consistency reliability (Cronbach's alpha) and construct-related validity (item convergent and discriminant validity). As unsatisfactory results were demonstrated, another structure was defined using a principal component analysis (PCA) combined with content of items. Psychometric properties of this new structure were assessed. Scores were compared between low, moderate and high compliance profile groups defined using data collected with the Travalert electronic device. RESULTS: Analyses were performed with the 169 patients who completed at least half of the EDSQ items. The hypothesized structure showed a Cronbach's alpha lower than 0.70 for four dimensions out of six and an overall poor construct-related validity (range of item-scale correlations: 0.00-0.68). The new structure obtained with the PCA included six dimensions: concern about treatment (five items); concern about disease (two items); satisfaction with patient-clinician relationship (five items); positive beliefs (three items); treatment convenience (three items); and self-declared compliance (three items). A score ranging from 0 to 100 was calculated for each dimension, with higher scores indicating more of the attribute referred to in the dimension. Internal consistency reliability was good (Cronbach's alpha greater than 0.70 for five dimensions). The structure offered good construct-related validity (range of item-scale correlations: 0.36-0.82). Ceiling effects of 21% and 49%, were observed for the satisfaction with patient-clinician relationship and self-declared compliance scores. Patients in low compliance profile group reported the lowest score for the satisfaction with patient-clinician relationship, positive beliefs, treatment convenience and self-declared compliance dimensions, and the highest score for the concern about treatment dimension. CONCLUSIONS: The scoring of the EDSQ was developed and the questionnaire proved to have satisfactory psychometric properties. EDSQ scores showed a promising relationship to compliance profiles. The EDSQ could be used in future studies.

Inpatient costs of endophthalmitis evaluated for the whole of France.

BACKGROUND: Endophthalmitis is a severe condition that requires hospitalization with at least day care. Information on the incidence rate, costs and consequences of endophthalmitis is scarce. OBJECTIVE: To estimate the number of patients with endophthalmitis hospitalized in France, as well as the average costs and hospital budget consequences. METHODS: French Programme de Médicalisation des Systèmes d'Information (PMSI) data for 2006, derived from the official DRG classification, were analysed. Data were extracted concerning the following primary diagnoses: 'purulent endophthalmitis', 'other endophthalmitis' and 'endophthalmitis associated with another disease'. Two durations of hospitalization were compared: the actual duration and a weighted DRG duration. The cost of hospitalization was weighted by the average DRG cost + daily hospital costs x the difference between the actual and weighted DRG days in hospital. All costs are presented in euro, year 2007 values. RESULTS: A total of 1518 patients (mean age 68.7 years; 47.1% male) experienced 1725 hospitalizations for endophthalmitis, including 1416 cases (82.1%) admitted to public hospitals. The majority of patients (79.1%) were classified by DRG codes that did not specify endophthalmitis (DRG 02M03Z). Most patients (1342) were given a drug injection and 510 underwent vitrectomy. Four patients died in hospital and 75 were transferred to other hospitals. The actual duration of hospitalization for endophthalmitis in public hospitals was 8.1 days (mean), whereas the average weighted DRG duration was 5.1 days, which underestimated the actual duration by 3 days. The average hospital cost was 3688 euro per patient, totalling 6,361,119 euro per annum for all public and private hospitalizations in France, including 223,723 euro as day care. If hospital funding was wholly based on DRG tariffs, the budget for endophthalmitis would be severely underestimated. The DRG inclusion of 'severe acute ocular infections' as a proxy for endophthalmitis dramatically underestimated its true cost by approximately 30%. CONCLUSION: For health economic evaluations, it is inappropriate to use DRG classifications as proxies for endophthalmitis. Expressed more generally, hospitalization cost analyses should not be based on any specific DRG, but always on the clinically relevant primary diagnosis. The PMSI clustering algorithm underestimates the hospital budgets required for endophthalmitis. Lastly, the PMSI (exhaustively reporting all hospitalizations) is best suited to capturing yearly endophthalmitis incidence rates, average costs and national health expenditure.

Postcataract acute endophthalmitis in France: national prospective survey.

PURPOSE: To report results of the National French Observational Database for Endophthalmitis (Observatoire National Des Endophtalmies [ONDE]). SETTING: Departments of ophthalmology at universities, general hospitals, and private clinics. METHODS: In this multicenter national interventional case series, data were collected prospectively between March 1, 2003, and November 1, 2004, from French ophthalmologists who answered a standardized 175-item questionnaire. The data were from patients with acute-onset endophthalmitis after cataract surgery. Before surgery, all 105 patients had received an official information card from the French Ophthalmological Society and provided written informed consent. RESULTS: The study comprised 105 patients. The median time from cataract extraction to endophthalmitis was 4 days (range 1 to 39 days). All but 1 patient had symptoms, with blurred vision being the most common. Initial visual acuity was 5/200 or better in 18.9% (18/95) of patients. Intraocular samples from 90.5% (95/105) of patients yielded 45 pathogens, of which 86.7% were gram positive. Treatments included intraocular antibiotic injections in 95.1% (98/103) of patients, intraocular steroid injections in 41.4% (41/99) of patients, and immediate vitrectomy in 14.0% (14/100) of patients. Visual acuity at 3 months was 20/100 in 64% of patients. CONCLUSIONS: The ONDE study disclosed important changes in French ophthalmic surgical practice 15 years after the first prospective endophthalmitis survey and 12 years after a United States study were published. Progress toward standardization of preventive methods (eg, patient information, increased systemic antibiotic efficacy, more frequent corticosteroid use) has contributed to fewer vitrectomies.

Corrected and uncorrected near and distance vision with ReSTOR compared to monofocal intraocular lens implantation after cataract surgery: a pooled analysis.

BACKGROUND/AIM: To evaluate distance and near vision-related benefit after implantation of ReSTOR multifocal intraocular lenses (IOLs) following cataract surgery. METHODS: Two prospective open-labeled nonrandomized studies were pooled. Patients' perception of benefit was assessed with the TyPE, administered at baseline and after each eye surgery. RESULTS: A total of 499 patients received ReSTOR IOLs, and 173 received monofocal IOLs. The distance vision of monofocal and ReSTOR patients improved equally with and without glasses. A greater improvement in near vision without glasses was reported by ReSTOR-implanted patients as early as after the 1st eye surgery (p < 0.0001). More ReSTOR patients than monofocal patients reported independence from glasses after the 1st eye surgery (64 vs. 52%; p = 0.0002). This difference had increased after the 2nd eye surgery (85 vs. 51%; p < 0.0001). CONCLUSIONS: The improvement in near vision without glasses was significantly more evident in ReSTOR patients, allowing the majority of them to be free of glasses.

Cost effectiveness of travoprost versus a fixed combination of latanoprost/timolol in patients with ocular hypertension or glaucoma: analysis based on the UK general practitioner research database.

OBJECTIVE: This study aimed to compare the cost effectiveness of travoprost versus a fixed combination of latanoprost/timolol as first-line therapies for ocular hypertension or glaucoma. METHODS: Patient charts were extracted from the UK General Practitioner Research Database. Patients with ocular hypertension or glaucoma who received first-line treatment with either travoprost or latanoprost/timolol and were followed up for >6 months were included. Treatment failure was defined as a treatment change or a glaucoma intervention (laser therapy or surgery). Time to treatment failure was compared using a Cox model and adjusted by the propensity score method. RESULTS: Eligible patients received either travoprost (n=639) or latanoprost/timolol (n=176). Their mean age was 70 years at diagnosis and 48.2% of patients were male. Patient characteristics did not differ significantly between treatment groups. Treatment failure rates at 1 year were 31.3% (travoprost) and 39.4% (latanoprost/timolol) and yielded a hazard ratio for failure in favour of travoprost (0.75; p<0.04) after adjusting for age, sex, co-morbidities and duration of follow-up. Adjusted annual costs of glaucoma management were significantly (p<0.001) less with travoprost (pound215.86) than with latanoprost/timolol (pound327.83). CONCLUSIONS: In everyday practice, travoprost was maintained longer than latanoprost/timolol as first-line therapy for glaucoma. The mean daily costs of travoprost were 50.8% less per patient than those of latanoprost/timolol. Despite adjustments, these results might be confounded, at least partially, by disease severity.

Modelling the lifetime economic consequences of glaucoma in France.

OBJECTIVE: To estimate the lifetime economic consequences of glaucoma in France. METHODS: A Markov model estimated the average discounted outcome and cost of glaucoma treatment over a patient's lifetime. Clinical states were defined as first- to fourth-line drugs, no treatment, laser therapy, surgery, blindness and death. After each failure (always after the fourth-line drug) patients could receive either laser treatment or surgery followed by no treatment, or a new treatment. A societal perspective was adopted. Sensitivity analyses were performed. RESULTS: Discounted medical costs were euro 7,322 for ocular hypertension treatment (OHT) and euro 8,488 for a glaucoma patient. Social costs of OHT and glaucoma patients exceeded medical costs. First-line use of the most effective drug would reduce medical and social costs. Societal willingness to pay for the vision benefit would equal the medical costs. Treatment initiated with the most effective drug is a cost saving strategy. CONCLUSIONS: Public health decisions in glaucoma treatment should take a broad economic view embracing the lifetime duration of the disease. There is still a place both within and outside the healthcare system for therapeutic innovations with important economic consequences that bring high added value to patients.

Association between visual acuity and medical and non-medical costs in patients with wet age-related macular degeneration in France, Germany and Italy.

INTRODUCTION: Exudative ('wet') age-related macular degeneration (ARMD) is the major cause of blindness in Western developed countries. Treatments aimed at preserving vision are already available and new compounds are under development. Micro-economics information will be pivotal to justifying forthcoming investment. OBJECTIVE: This study sought to investigate the costs of exudative ARMD in patients who were actively treated at ophthalmology referral centres in three European countries: France, Germany and Italy. METHOD: This cross-sectional observational study was conducted in France, Germany and Italy in 2004. The following data were collected: ARMD description, visual acuity (VA), and the medical and non-medical resources used for ARMD in the preceding year. The economic perspective was that of society. ANOVA for cost variables estimated the impact of ARMD per eye, adjusted for sex and age. Both hospital and ambulatory eye centres were included. Patients with exudative ARMD were stratified into four levels of severity using VA thresholds of 20/200 for the worst eye (WE) and 20/40 for the best eye (BE). The main outcome measure was medical and non-medical costs. RESULTS: 360 patients were included (females 60%; mean age 77 years; mean interval since diagnosis 2.3 years). The two groups with the greatest difference in severity of VA loss consisted of BE >or= 20/40, WE >or= 20/200 (27.2% of patients) and BE <20/40, WE <20/200 (25.5% of patients). Total cost was two-thirds medical and one-third non-medical. Total costs increased with ARMD severity and were 1.1-2 times greater for severe disease compared with less severe disease. Average medical costs (2004 values) in France were euro 3714, compared with euro 1810 in Germany and euro 2020 in Italy, and showed slight increases with ARMD severity. Non-medical costs were significantly higher for patients with severe disease and highest in Germany. CONCLUSION: The impact of ARMD on costs was considerable and a positive correlation was found between total costs and ARMD severity. Differences among countries were partly explained by differences in customary care delivery.

Patient-reported benefit of ReSTOR multi-focal intraocular lenses after cataract surgery: results of principal component analysis on clinical trial data.

BACKGROUND: Restoration of functional distance and near vision independently of additional correction remains a goal for cataract surgery. ReSTOR, a new multi-focal intraocular lens (IOL) addresses this issue with an improvement in both distance and near vision, often without need for glasses. This analysis attempted to discuss the patient-reported benefit of ReSTOR using a full but organised representation of data. METHODS: Two non-randomised, open-label clinical trials conducted in Europe and the United-States were conducted to compare the efficacy of ReSTOR to AcrySof mono-focal IOLs. A total of 710 patients in need of bilateral cataract extraction were included in the pooled study. The TyPE, a patient questionnaire, was fully completed by 672 of them before and after each eye surgery. The TyPE, composed of 67 items measuring overall visual functioning in both conditions (with and without wearing glasses), evaluates limitations, troubles and satisfaction in distance and near vision. A principal component analysis (PCA) of the TyPE questionnaire was performed on pooled data from baseline and post-surgery observations in order to fully represent the change in the TyPE data over time. ReSTOR and mono-focal groups were used as illustrative variables. The coordinates of the first 2 factors were compared between visits and between IOLs (ReSTOR vs. mono-focal), using paired t-tests and t-tests, respectively. RESULTS: The first factor of the PCA explained 55% of the variance and represented 'visual functioning and patient satisfaction'. The second factor explained 6% of the variance and was interpreted as 'independence from glasses'. An overall difference in factorial coordinates in both factors was seen between baseline and the first eye surgery, and between the first and the second eye surgery. No difference between ReSTOR and mono-focal IOL groups was observed at baseline. After surgery, ReSTOR treated-patients had higher coordinates on both "visual functioning and satisfaction" and "independence from glasses" factors. Findings observed on the factorial plan were supported by statistical comparisons of factorial coordinates. CONCLUSION: Both mono-focal and ReSTOR-implanted patients improved their visual functioning after bilateral cataract surgery. Moreover, ReSTOR patients reported an additional benefit in independence from glasses as well as in visual functioning and patient satisfaction.

Modelling lifetime cost consequences of ReSTOR in cataract surgery in four European countries.

BACKGROUND: To compare the lifetime costs of liberating patients from spectacles after cataract surgery by implanting the multifocal intraocular lens (IOL) 'ReSTOR' versus monofocal IOLs in France, Italy, Germany and Spain. METHODS: A Markov model was created to follow patient cohorts from cataract surgery until death. Prevalence rates of patients not needing spectacles after cataract surgery were obtained from clinical trials. Resource utilisation included implant surgery, IOLs, spectacles, visits to ophthalmologists and eye centres, transport, and time lost by patients. Economic perspectives were those of Society and Sickness Funds (SFs). RESULTS: The mean number of spectacles purchased after ReSTOR was 1.34-1.61 and after monofocal IOLs 6.05-7.27. From the societal perspective, total cost estimates discounted by 3% were between 3,551 euros and 4,052 euros with ReSTOR compared to 3,989 euros and 5,548 euros with monofocal IOLs. Undiscounted savings related to ReSTOR ranged from 815 euros to 2,164 euros. From the SFs' perspective total cost estimates discounted by 3% were between 2,150 euros and 2,524 euros with ReSTOR compared to 2,324 euros and 2,610 euros with monofocal IOLs. Savings related to ReSTOR, once costs discounted, ranged from 61 euros to 219 euros. Discount and spectacle freedom prevalence rates were the most sensitive parameters. CONCLUSION: The bulk of the savings related to ReSTOR were realized outside the SF. From both a societal and SF perspective, savings, after a 3% discounting, achieved by liberating patients from spectacles counterbalanced the initially higher cost of ReSTOR. ReSTOR is a cost saving alternative to spectacles for patients requiring cataract surgery.

Assessment of the cost effectiveness of travoprost versus latanoprost as single agents for treatment of glaucoma in France.

BACKGROUND AND OBJECTIVE: Control of intraocular pressure (IOP) is a major factor in avoiding visual impairment related to glaucoma. Both the cost and the effectiveness of therapy should be considered when initiating this lifelong treatment. The aim of this study was to assess the cost effectiveness of travoprost versus latanoprost as single agents for the treatment of glaucoma in France. METHODS: Two surveys, one documenting efficacy and the other costs, were used to provide data for a Markov model. The model reproduced the 5-year course of patients receiving a prostaglandin analogue, travoprost or latanoprost, as monotherapy. The effectiveness criterion was fitted with a Weibull distribution from a national study. Transition probabilities and costs per treatment line were extracted from two French observational databases. Bootstrap techniques were implemented to drive the probabilistic sensitivity analyses. The study compared both treatments given once daily as monotherapy to ambulatory patients with primary open-angle glaucoma or ocular hypertension. The main outcome measure was mean time to treatment change (MTTC). Possible treatment changes were the addition of adjunctive medication, treatment substitution, laser therapy or surgery. After laser therapy or surgery, patients could continue with no treatment or proceed to prostaglandin analogue as monotherapy or treatment substitution. IOP was stratified at treatment onset as < or =20, 21-23 and > or =24 mmHg, respectively. All costs were expressed in 2005 euros. RESULTS: MTTC was 44.3 months for travoprost and 37.8 for latanoprost. Additional 5-year costs for travoprost were euro51, resulting in an incremental cost-effectiveness ratio without treatment change of euro95 per year. Of patients treated with latanoprost, 1.9% underwent laser therapy or surgery, compared with 1.2% of patients treated with travoprost. The results differed with baseline IOP values, such that 55.6%, 53.9% and 50.4% of patients with pretreatment IOP values of < or =20, 21-23 and > or =24 mmHg, respectively, continued to receive travoprost treatment at 5 years, compared with 32.3%, 26.1% and 26.1% of patients, respectively, receiving latanoprost. Thus, incremental cost-effectiveness ratios (ICERs) without treatment change were euro140, euro45 and euro123 per year, respectively. CONCLUSION: Travoprost demonstrated a longer effectiveness profile than latanoprost and minimized early treatment changes. The smaller proportion of patients needing a new treatment, laser therapy or surgery virtually compensated for the higher travoprost acquisition cost. Overall, travoprost is cost effective compared with latanoprost, and is most cost effective in patients with pretreatment IOPs between 21 and 23 mmHg.

Intraocular pressure control with latanoprost/timolol and travoprost/timolol fixed combinations : a retrospective, multicentre, cross-sectional study.

OBJECTIVE: The aim of this study was to confirm randomized clinical trial results showing that a fixed timolol/travoprost combination (TT; DuoTrav) controls intraocular pressure (IOP) better than a fixed timolol/latanoprost combination (TL; Xalacom) in everyday ophthalmic practice, when measured in the morning and >24 hours after instillation. METHODS: Patients with ocular hypertension or primary open angle glaucoma stabilized on TT or TL were included in this retrospective cross-sectional study. Data on demographics, medical history and previous treatments were extracted from the patients' medical records. Last treatment instillation times and IOP values were recorded at clinic visits. Treatments were compared by analyses of variance, logistic regressions and propensity scores adjusted for confounding factors. RESULTS: Out of 316 patients included, 124 instilled TT, 192 instilled TL and 266 (84.2%) overall had instilled their eye drops within 24 hours. The patients' mean age was 64.5 years and 51.6% were female. Treatment groups were comparable except for longer disease and treatment durations in TL recipients. Worse eye mean IOPs were 25.8 mmHg at diagnosis and 21.9 mmHg on starting their designated fixed combination treatment. The best IOP control was provided by TT instillations (mean IOP 17.1 and 19.0 mmHg in the TT and TL groups, respectively; p < 0.001). This difference was reinforced by results in the subgroup of patients who instilled treatment >24 hours prior to IOP measurement (mean IOP 17.0 and 20.3 mmHg in the TT and TL groups, respectively; p < 0.004). Also, 82.6% of TT patients satisfied their ophthalmologists' IOP targets versus 51.1% of TL patients (p < 0.001). All significant differences persisted after adjustment for confounding factors. CONCLUSION: This study, conducted in routine ophthalmic practice, confirmed published clinical trial results showing that TT provides better IOP control than TL when measured in the morning, and that travoprost has longer-lasting residual effects than latanoprost when IOP is measured >24 hours after instillation. However, readers should interpret these findings in the context of a cross-sectional observational study conducted in a naturalistic setting.

Costs and persistence of brimonidine versus brinzolamide in everyday glaucoma care: an analysis conducted on the UK General Practitioner Research Database.

OBJECTIVE: To compare the persistence and costs of brimonidine versus brinzolamide therapy according to data collected by the UK General Practitioner Research Database (GPRD). METHODS: Patients with diagnoses of ocular hypertension or glaucoma, or treated for glaucoma by surgery or laser therapy were identified. Selected patients were prescribed either brimonidine or brinzolamide as monotherapy. Treatment failure was defined as a glaucoma prescription change (adding, removing or replacing a drug, or initiating surgery or laser therapy). Times to treatment failure were compared with an adjusted Cox model using a propensity score method. RESULTS: A total of 2,172 patients received brimonidine and 485 brinzolamide. Mean age was 69.5 years and 46.4% were male. Age and gender did not differ significantly whereas disease duration was longer with brinzolamide. Treatment failure at 1 year was experienced by 47.7% of patients given brinzolamide and by 55.9% given brimonidine (p<0.001). The hazard ratio for failure was less with brinzolamide (0.79: p<0.001) compared to brimonidine, after adjusting for age, gender, comorbidities and duration of follow-up. Adjusted annual costs of glaucoma management (in pound2005) were significantly (p<0.0042) lower with brinzolamide (pound196) than brimonidine (pound230). CONCLUSIONS: According to data from everyday practice collected by the UK GPRD, brinzolamide was found to be more persistent than brimonidine when given as glaucoma monotherapy. Patients continued longer with brinzolamide treatment at a lower cost.

Public health impact of neovascular age-related macular degeneration treatments extrapolated from visual acuity.

PURPOSE: To estimate the potential public health impact of treatment with new medications intended to preserve vision in patients with neovascular age-related macular degeneration (AMD). METHODS: A Markov model was used to simulate the natural history of AMD over the lifetime of patients with diagnosed neovascular AMD from clinical trials and epidemiologic surveys. It applied to a cohort of patients aged 75 years, with newly diagnosed neovascular AMD in one eye, whose visual acuity was 0.7 logMAR. Probabilities were calculated for the risk of AMD in the remaining eye and for premature mortality. Results of the model were expressed as the duration of low vision (worse eye VA>1.0 and better eye VA>0.7 logMAR) and blindness (bilateral VA >1.0 logMAR). Health consequences of blindness and low vision were estimated for depression, hip fractures, institutionalization, and life expectancy. RESULTS: For AMD patients with a 50% probability of VA >1.0 logMAR at 1 year, in one eye, the probability of lifetime bilateral blindness was >47%. The patients would live approximately 7 years with monocular vision >1.0 logMAR and an additional 4 years with bilateral blindness and a >15% probability of depression due to AMD. Life expectancy was decreased by approximately 2 years, >90/1000 patients would sustain a new hip fracture, and 1.5% of the patients would require institutional care for visual impairment due to AMD. To achieve a defined public health outcome (visual impairment and consequent comorbidity), it was necessary for the VA effectiveness of new treatments to increase in parallel with disease severity. CONCLUSIONS: Comorbidity related to visual impairment contributes significantly to the public health impact of AMD. Aggressive lesions need highly effective treatments. Models may be used to compare the public health impact of placebo-controlled clinical trial results.

Anxiety and depression prevalence rates in age-related macular degeneration.

PURPOSE: To estimate the prevalence rates of depression and anxiety in patients with wet age-related macular degeneration (AMD) and the relationship with visual acuity and to develop a simple algorithm for depression screening. METHODS: This cross-sectional, prospective, observational, multicenter study was performed in France, Germany, and Italy. Retina specialists at 10 centers per country each enrolled 12 consecutive patients with wet ARMD. Patients were stratified into four severity groups by using best eye (BE) and worst eye (WE) visual acuity (VA) thresholds (BE:VA 20/40 and WE:VA 20/200). Patients rated themselves on the Hospital Anxiety and Depression Scale (HADS). Analysis of variance was performed to estimate the effect of VA severity levels on HADS scores adjusted on age, gender, and country. RESULTS: Patients (females 60%) were recruited, with a mean age of 77 years and 2.3 years' disease duration. Mean BE:VA at inclusion was 0.49 logMar (logarithm of the minimum angled of resolution) and WE:VA 1.0 logMar. The prevalence of severe depression increased from 0% (BE:VA > or = 20/40+WE:VA > or = 20/200) to 7.6% (BE:VA < 20/40+WE:VA < 20/200), whereas anxiety was unrelated to VA loss. Moreover, total depression scores were strongly associated with VA severity (P = 0.006), but not total anxiety scores (P = 0.840). Responses to two HADS items ("I still enjoy things I used to enjoy"; "I can enjoy a good book or radio or television program") identified 95% of severely to moderately depressed patients. CONCLUSIONS: Self-rated depression in patients with AMD was associated with VA severity level. It should, therefore, be relatively easy for ophthalmologists to implement the screening procedure and refer identified patients to psychiatrists for proper assessment and treatment.