Cost-Utility of Anti-Vascular Endothelial Growth Factor Treatment for Macular Edema Secondary to Central Retinal Vein Occlusion.

PURPOSE: To evaluate the cost-utility of treatment for macular edema in central retinal vein occlusion (CRVO) using intravitreal injections of the anti-vascular endothelial growth factor (VEGF) agents bevacizumab, ranibizumab, and aflibercept. DESIGN: Decision analysis model of cost-utility. PARTICIPANTS: Data from study participants in the Lucentis, Eylea, Avastin in Vein Occlusion (LEAVO) study. METHODS: A decision analysis of a disease simulation model was used to calculate comparative cost-utility of intravitreal bevacizumab (IVB), intravitreal ranibizumab (IVR), and intravitreal aflibercept (IVA) for the treatment of macular edema associated with CRVO based on data from the LEAVO study. Center for Medicare and Medicaid Services data were used to calculate associated modeled costs in a hospital- or facility-based and nonfacility setting from a third-party payer perspective, and societal costs also were calculated. Cost utility was calculated based on the preserved visual utility during the 2 years of the study and also by estimating utility for the expected lifetime. MAIN OUTCOME MEASURES: Cost of treatment, cost per quality-adjusted life-year (QALY), and incremental cost-effectiveness ratio (ICER). RESULTS: From the third-party payer perspective, the estimated lifetime costs per QALY in the facility and nonfacility settings were $39 325 and $17 944, respectively, for IVB; $114 095 and $92 653, respectively, for IVR; and $78 935 and $63 270, respectively, for IVA. From the societal perspective, the estimated lifetime costs per QALY in the facility setting were $52 754 for IVB, $128 242 for IVR, and $86 262 for IVA. The ICER of IVA compared with that of IVB was $153 633/QALY from the third-party facility setting and $152 992/QALY from the societal perspective. The use of IVB compared with IVR and IVA compared with IVR were cost-saving interventions (ICER, <0) regardless of the perspective or setting. CONCLUSIONS: In the treatment of macular edema in CRVO, IVB yields the best cost utility among the 3 anti-VEGF agents modeled. Intravitreal aflibercept maintains acceptable lifetime cost per QALY while having a favorable cost utility compared with IVR.

GAP IN CAPILLARY PERFUSION AND BURDEN OF TREATMENT IN BRANCH RETINAL VEIN OCCLUSION: A Wide-Field Optical Coherence Tomography Angiography Study.

PURPOSE: To evaluate correlations between the burden of antivascular endothelial growth factor treatment and microperfusion status in superficial capillary plexus and deep capillary plexus (SCP and DCP) using wide-field optical coherence tomography angiography. METHODS: A total 19 eyes with branch retinal vein occlusion were included in this retrospective study. Area of foveal avascular zone, capillary nonperfusion area, vascular density, and perfusion gap were compared between superficial capillary plexus and DCP. Internal areas of 3, 6, and 12 mm in diameter around the fovea were analyzed separately. RESULTS: The mean number of injections per months was 0.20 ± 0.12. The number of antivascular endothelial growth factor injections per month showed a significant correlation with perfusion gap in 12 mm area (P = 0.010), but not with perfusion gap in 3-mm or 6-mm area. Correlations were also found between the final best-corrected visual acuity and vascular density in the 12 mm area of DCP (P = 0.031) and foveal avascular zone area (P = 0.033). CONCLUSION: Wide-field optical coherence tomography angiography is very useful for assessing the microperfusion status in branch retinal vein occlusion. In extended field of view (12 mm × 12 mm), a larger perfusion gap was associated with frequent requirements of antivascular endothelial growth factor injections for macular edema. Reduction in vessel density was significantly correlated with poor visual outcome.

Effect of funding source on reporting bias in studies of intravitreal anti-vascular endothelial growth factor therapy for retinal vein occlusion.

PURPOSE: To examine the relationship between industry funding and outcome reporting bias in high-quality studies investigating the use of intravitreal anti-vascular endothelial growth factor (VEGF) agents for patients with macular oedema secondary to branch or central retinal vein occlusion (RVO). METHODS: This systematic review in PubMed and Ovid MEDLINE examined all randomized clinical trials and meta-analyses published in journals with impact factor of ≥2 that investigated effectiveness of intravitreal anti-VEGF therapy in patients with RVO. The main outcome measure was correspondence between statistical outcome and abstract conclusion wording. RESULTS: Forty-five studies met inclusion criteria; 38 (84%) showed correspondence between outcome and abstract conclusion without difference between industry-funded and nonindustry-funded publications (p = 0.39) or between publications in journals with impact factor ≥3 versus <3 (p = 0.96). CONCLUSION: In high-quality studies of intravitreal anti-VEGF therapy for RVO, neither industry funding nor journal impact factor affected the rate of outcome reporting bias.

Analysis of costs associated with the management and morbidity of diabetic macular oedema and macular oedema secondary to retinal vein occlusion. / Análisis de los costes asociados al manejo y morbilidad del edema macular diabético y el edema macular secundario a oclusión venosa de la retina.

OBJECTIVE: To analyse the disease burden in patients with diabetic macular oedema (DMO) or with retinal vein occlusion macular oedema (RVOMO) from a societal perspective. METHODS: Observational, cross-sectional, multicentre study conducted on patients >18 years old diagnosed with uni- or bilateral DMO or unilateral RVOMO. Data on the use of health resources from diagnosis was collected, and the impact of disease on work life was assessed. Costs were annualised (euros, January 2014). Differences were contrasted using Chi-squared test (or Fisher Exact test), Mann Whitney-U test or Kruskal-Wallis test (Dunn contrast). RESULTS: A total of 448 patients were included (DMO 255; RVOMO 193). There were significant differences in costs of diagnosis: RVOMO €1856, bilateral DMO €1661, and unilateral DMO €1401 (P<.001) and the aggregate medical costs: RVOMO €4639, bilateral DMO 6275€ and unilateral DMO 6269€ (P<.001). Cost by permanent time off work was higher in bilateral DMO €11712, than in unilateral DMO €4284€, and than in RVOMO €1052 (P<.05). Linear regression analysis showed that variables associated with direct health costs were: Diagnosis (bilateral DMO was associated with higher cost), as well as number of days in hospital, number of visits, time of observation, and number of days of time off work. CONCLUSIONS: Patients with bilateral DMO are associated with a higher direct health cost, as well as a higher indirect cost by impact of the disease on work life.

Comparison of Outcomes and Costs of Ranibizumab and Aflibercept Treatment in Real-Life.

BACKGROUND: Treatment efficacy and costs of anti-VEGF drugs have not been studied in clinical routine. OBJECTIVE: To compare treatment costs and clinical outcomes of the medications when adjusting for patients' characteristics and clinical status. DESIGN: Comparative study. SETTING: The largest public ophthalmologic clinic in Switzerland. PATIENTS: Health care claims data of patients with age-related macular degeneration, diabetic macula edema and retinal vein occlusion were matched to clinical and outcome data. MEASUREMENTS: Patients' underlying condition, gender, age, visual acuity and retinal thickness at baseline and after completing the loading phase, the total number of injections per treatment, the visual outcome and vital status was secured. RESULTS: We included 315 patients (19595 claims) with a follow-up time of 1 to 99 months (mean 32.7, SD 25.8) covering the years 2006-2014. Mean age was 78 years (SD 9.3) and 200 (63.5%) were female. At baseline, the mean number of letters was 55.6 (SD 16.3) and the central retinal thickness was 400.1 µm (SD 110.1). Patients received a mean number of 15.1 injections (SD 13.7; range 1 to 85). Compared to AMD, adjusted cost per month were significantly higher (+2174.88 CHF, 95%CI: 1094.50-3255.27; p<0.001) for patients with DME, while cost per month for RVO were slightly but not significantly higher. (+284.71 CHF, 95% CI: -866.73-1436.15; p = 0.627). CONCLUSIONS: Patients with DME are almost twice as expensive as AMD and RVO patients. Cost excess occurs with non-ophthalmologic interventions. The currently licensed anti-VEGF medications did not differ in costs, injection frequency and clinical outcomes. Linking health care claims to clinical data is a useful tool to examine routine clinical care.

Direct medical costs and resource use for treating central and branch retinal vein occlusion in commercially insured working-age and Medicare populations.

PURPOSE: To quantify the burden of illness for incident branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) in a commercially insured working-age (commercial) and Medicare US population. METHODS: Retrospective cohort analysis of health care claims from 2003 through 2008 from commercial and Medicare patients with ≥2 outpatient diagnoses for BRVO or CRVO. The index date was the first retinal vein occlusion diagnosis. Patients with medical and pharmacy benefits were followed ≥1 year preindex and then between 1 year and 3 years postindex. Incidence and prevalence of retinal vein occlusion was determined. Burden of illness was compared with matched control subjects without retinal vein occlusion. RESULTS: The commercial sample comprised 1,188 CRVO and 2,252 BRVO cases, whereas the Medicare sample had 2,739 CRVO and 4,573 BRVO cases. Adjusted ratio of case-to-control, all-cause expenditures for commercial patients at 1 year and 3 years postindex were 1.88 and 1.68, respectively, for BRVO and 1.42 and 1.36, respectively, for CRVO. For Medicare patients, these were 1.29 and 1.13, respectively, for BRVO and 1.23 and 1.14, respectively, for CRVO. All comparisons were significant (P < 0.001). CONCLUSION: Health care utilization and expenditures for commercially insured working-age and Medicare patients with BRVO or CRVO were significantly greater than those for control subjects. Retinal vein occlusion development may be a marker for the increased severity of systemic vascular disease.

Treat-and-extend intravitreal bevacizumab for branch retinal vein occlusion.

BACKGROUND AND OBJECTIVE: To determine the effectiveness and direct medical costs of treat-and-extend (TAE) intravitreal bevacizumab (IVB) for the treatment of branch retinal vein occlusion (BRVO)-associated macular edema (ME). PATIENTS AND METHODS: Retrospective chart review of 52 consecutive patients diagnosed with BRVO-associated ME treated with IVB using a TAE protocol. RESULTS: Mean change in logMAR vision was -0.30 (P < .001), and mean change in central macular thickness was -244.0 µm (P < .001). The mean number of injections was 8.2 (95% CI; 7.8 to 8.6). The yearly average direct cost of the TAE regimen was calculated to be $2,580.26 per patient. CONCLUSION: Treatment of BRVO-associated ME with IVB using a TAE regimen resulted in similar visual outcomes and number of intravitreal injections as did as-needed treatment with 0.5 mg ranibizumab conducted in phase 3 trials but with fewer visits and lower annual medical costs.

Treating retinal vein occlusions in France, Germany, and Italy: an analysis of treatment patterns, resource consumption, and costs.

PURPOSE: To describe treatment patterns among patients with central or branch retinal vein occlusion (CRVO or BRVO) in France, Germany, and Italy, and to estimate retinal vein occlusion (RVO)-related direct medical costs. METHODS: We used a retrospective chart review to determine 18-month RVO-related resource utilization and calculate 12-month health care costs. Country-specific unit costs (€) were assigned to each resource from the perspective of the health care payer. Costs for France and Germany were based on 2005, and for Italy on 2007 values. RESULTS: Data from a total of 109 BRVO and 119 patients with CRVO were used in the analysis. Laser therapy was the most commonly used intervention in Germany, for both CRVO and patients with BRVO (95%-98% of treatments), while patients in France with either condition had triamcinolone injections most often (63%-67% of treatments). Injections were also administered frequently in Italy and were the most common treatment for CRVO (50%), whereas patients with BRVO used laser therapy most often (41%). Inpatient treatment was most common in Germany (42% of CRVO and 34% of patients with BRVO), and did not occur at all in Italy except for day admissions. Total costs were higher for patients with CRVO in all countries. Most costs in Italy and France were attributable to outpatient treatment. In Germany, hospitalization made up the largest proportion of costs (80%), although more patients used outpatient services. CONCLUSIONS: Approaches to treating BRVO and CRVO vary across European countries. Development of agreed-upon guidelines would support consistency in patient care and reimbursement policy.

The burden of disease of retinal vein occlusion: review of the literature.

Retinal vein occlusion (RVO) is the second most common cause of vision loss due to retinal vascular disease. A literature review was undertaken to understand the epidemiology, clinical consequence, current practice patterns, and cost of RVO. Pertinent articles were identified by computerized searches of the English language literature in MEDLINE supplemented with electronic and manual searches of society/association proceedings and bibliographies of electronically identified sources. Population-based studies report a prevalence rate of 0.5-2.0% for branch RVO and 0.1-0.2% for central RVO. The 15-year incidence rate is estimated to be 1.8% for branch RVO and 0.2% for central RVO. Patients with RVO report lower vision-related quality of life than those without ocular disease. Available treatment options are limited. Until recently there was no treatment for central RVO. Laser photocoagulation is only recommended for branch RVO in patients who have not experienced severe vision loss. Emerging evidence on the effectiveness of intravitreal anti-vascular endothelial growth factor therapy and dexamethasone intravitreal implant is promising. Information on the treatment patterns and cost of RVO is extremely limited with one retrospective analysis of secondary insurance payment data identified and limited to the United States population only. A better understanding of the economic and societal impact of RVO will help decision makers evaluate emerging medical interventions for this sight-threatening disease.

Economic considerations of macular edema therapies.

PURPOSE: To relate costs and treatment benefits for diabetic macular edema (DME), branch retinal vein occlusion (BRVO), and central retinal vein occlusion (CRVO). DESIGN: A model of resource use, outcomes, and cost-effectiveness and utility. PARTICIPANTS: None. METHODS: Results from published clinical trials (index studies) of laser, intravitreal corticosteroids, intravitreal anti-vascular endothelial growth factor (VEGF) agents, and vitrectomy trials were used to ascertain visual benefit and clinical protocols. Calculations followed from the costs of 1 year of treatment for each treatment modality and the visual benefits as ascertained. MAIN OUTCOME MEASURES: Visual acuity (VA) saved, cost of therapy, cost per line saved, cost per line-year saved, and costs per quality-adjusted life years (QALYs). RESULTS: The lines saved for DME (0.26-2.02), BRVO (0.74-4.92), and CRVO (1.2-3.75) yielded calculations of costs/line of saved VA for DME ($1329-$11,609), BRVO ($494-$13,039), and CRVO ($704-$7611); costs/line-year for DME ($60-$561), BRVO ($25-$754), and CRVO ($45-$473); and costs/QALY ($824 to $25,566). CONCLUSIONS: Relative costs and benefits should be considered in perspective when applying and developing treatment strategies.

Resource use and costs of branch and central retinal vein occlusion in the elderly.

OBJECTIVE: To examine the incidence, prevalence, resource use, and costs associated with branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) in elderly patients. RESEARCH DESIGN AND METHODS: In a retrospective cohort study of a nationally representative sample of Medicare beneficiaries from 2001 through 2006, the authors identified patients with BRVO (n = 10,682) and CRVO (n = 6236) and controls with hypertension (n = 49,524) and glaucoma (n = 49,569) but no retinal vein occlusion. Incident cases were those with no claims listing a diagnosis for the same type of retinal vein occlusion in the previous 12 months. Prevalence was defined as the number of beneficiaries with a diagnosis of BRVO or CRVO. The authors summed Medicare reimbursements for all claims and used generalized linear models to estimate the effects of BRVO and CRVO on 1-year and 3-year costs compared with hypertension and glaucoma control groups. The authors also examined trends in the use of diagnostic and treatment modalities. MAIN OUTCOME MEASURES: Resource use (fluorescein angiography, optical coherence tomography, intravitreal injection, laser photocoagulation, and vitrectomy) and direct medical costs (total Medicare reimbursement amounts as recorded on each inpatient, outpatient, home health, skilled nursing, hospice, durable medical equipment, and professional service claim) at 1 year and 3 years. RESULTS: After adjustment for baseline characteristics, BRVO was associated with 16% higher 1-year costs and 12% higher 3-year costs compared with hypertension and 18% higher 1-year costs and 13% higher 3-year costs compared with glaucoma. CRVO was associated with 22% higher 1-year costs and 15% higher 3-year costs compared with hypertension and 24% higher 1-year costs and 16% higher 3-year costs compared with glaucoma. Use of fluorescein angiography and optical coherence tomography increased during the study. Use of intravitreal injections increased from less than 1% of patients overall to greater than 13% for BRVO and 16% for CRVO. The incidence of BRVO declined slightly during the study period, whereas the incidence of CRVO remained relatively flat. Prevalence increased in both groups. LIMITATIONS: The results may not be generalizable to younger patients or managed-care beneficiaries. The study included only direct costs to Medicare, not nonmedical expenditures or outpatient prescription medications. Diagnosis and procedure codes may not have been complete. The study could not account for clinical variables, such as the amount of vision loss. It was not feasible to adjust for whether one or both eyes were affected or treated. CONCLUSIONS: Although not common in the Medicare population, BRVO and CRVO are important independent predictors of total medical costs. Diagnostic and treatment modalities have changed over time.

Incremental cost-effectiveness of laser therapy for visual loss secondary to branch retinal vein occlusion.

PURPOSE: To ascertain the incremental cost-effectiveness of therapeutic interventions for improving visual loss associated with branch retinal vein occlusion. METHODS: A cost-utility analysis incorporating data from the Branch Vein Occlusion Study Group was performed using patient-based preferences obtained from time tradeoff utility analysis, decision analysis with Markov modeling, and economic modeling with future value analysis. The cost-effectiveness results are expressed in dollars/QALY (dollars expended per quality-adjusted life-year) gained. This unique model takes into account the visual acuity in the better seeing eye and the recurrent risk for visual loss in the contralateral eye. RESULTS: Laser therapy for macular edema secondary to branch retinal vein occlusion was associated with an incremental dollars/QALY gained of 6118 dollars (in year 2000 U.S. dollars). Two-way sensitivity analysis, varying the discount rate and the proportion of patients developing a vascular occlusion in the contralateral eye, revealed a range of dollars/QALY gained from 3370 dollars to 19,299 dollars. CONCLUSIONS: Laser therapy appears to be a cost-effective intervention for improving visual loss associated with macular edema secondary to branch retinal vein occlusion. Variants of the methodology employed to calculate the incremental cost-effectiveness of this intervention can be widely applied across all specialties in medicine.