Lifetime Outcomes of Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration.

Importance: Neovascular age-related macular degeneration (nAMD), the largest single cause of irreversible severe vision loss in high-income countries, can now be treated with vascular endothelial growth factor (VEGF) inhibitors, but to our knowledge, no data on lifetime outcomes are available. Objective: To determine visual acuity (VA) outcomes of anti-VEGF treatment for nAMD in both eyes for patients' remaining lifetime. Design, Setting, and Participants: Multistate modeling using real-world cohort data of 3192 patients with nAMD (>67 000 visits) treated in routine eye clinics in Australia, New Zealand, and Switzerland. Data were analyzed between 2007 and 2015. Exposures: Intravitreal anti-VEGF treatment at the treating physician's discretion and prospective data collection in standardized registry. Main Outcomes and Measures: Visual acuity in both eyes over the remaining lifetime. Results: For the mean remaining lifetime of 11 years, an estimated 12% (n = 371; 95% CI, 345-400) of the sample retained driving VA and an estimated 15% (n = 463; 95% CI, 434-495) reading VA in at least 1 eye. At that time, an estimated 82% of the sample (n = 2629; 95% CI, 2590-2660) had dropped out. Younger age at baseline and more injections during the first year of treatment were associated with better long-term outcomes. Conclusions and Relevance: Anti-VEGF treatment was associated with preserved useful visual acuity in almost 20% of patients over their average remaining lifetime. More than 80% of patients will cease treatment over that time, having likely experienced a deterioration of vision beforehand. This is a remarkable outcome compared with outcomes without intervention, which lead to legal blindness within 3 years of disease onset in 80% of those affected. These findings underline the public health necessity of providing anti-VEGF treatment to persons in need.

ORCA study: real-world versus reading centre assessment of disease activity of neovascular age-related macular degeneration (nAMD).

BACKGROUND/AIMS: The prospective, non-interventional ORCA module of the OCEAN study (Observation of Treatment Patterns with Lucentis in Approved Indications) evaluated the qualiy of spectral domain-optical coherence tomography (SD-OCT) image interpretation and treatment decisions by clinicians in Germany and the impact on visual outcomes over 24 months in patients with neovascular age-related macular degeneration (nAMD). METHODS: 2286 SD-OCT scans of 205 eyes were independently evaluated by clinicians and reading centres (RCs) regarding signs of choroidal neovascularisation (CNV) activity, including presence of intraretinal fluid, subretinal fluid, and/or increase in pigment epithelial detachments. Agreement between clinicians and RCs was calculated. Treatment decisions by clinicians and the impact on treatment outcomes were evaluated. RESULTS: CNV activity was detected by RCs on 1578 scans (69.0%) and by clinicians on 1392 scans (60.9%), with agreement in 74.9% of cases. Of the 1578 scans with RC detected CNV activity, anti-vascular endothelial growth factor injections were performed by clinicians in only 35.5% (560/1578). In 19.7% of cases (311/1578), lack of treatment was justified by patients request, termination criteria or chronic cystoid spaces without other signs for CNV activity. In 44.8% of cases (707/1578) with RC detected CNV activity, clinicians claimed no treatment was necessary despite having correctly detected CNV activity in about 2/3 of these cases. In 34% of cases with presumed undertreatment, visual acuity declined in the following visit. CONCLUSION: Although broad agreement on CNV activity parameters was observed between clinicians and RCs, correct identification of CNV activity did not always lead to the initiation of (re-)treatment. To preserve vision over time, correct interpretation of SD-OCT scans and careful retreatment decisions are required. TRIAL REGISTRATION NUMBER: NCT02194803.

Economic Value of Anti-Vascular Endothelial Growth Factor Treatment for Patients With Wet Age-Related Macular Degeneration in the United States.

Importance: Anti-vascular endothelial growth factor (anti-VEGF) is a breakthrough treatment for wet age-related macular degeneration (wAMD), the most common cause of blindness in western countries. Anti-VEGF treatment prevents vision loss and has been shown to produce vision gains lasting as long as 5 years. Although this treatment is costly, the benefits associated with vision gains are large. Objective: To estimate the economic value of benefits, costs for patients with wAMD, and societal value in the United States generated from vision improvement associated with anti-VEGF treatment. Design, Setting, and Participants: This economic evaluation study used data from the published literature to simulate vision outcomes for a cohort of 168 820 patients with wAMD aged 65 years or older and to translate them into economic variables. Data were collected and analyzed from March 2018 to November 2018. Main Outcomes and Measures: Main outcomes included patient benefits, costs, and societal value. Each outcome was estimated for a newly diagnosed cohort and the full population across 5 years, with a focus on year 3 as the primary outcome because data beyond that point may be less representative of the general population. Drug costs were the weighted mean across anti-VEGF therapies. Two current treatment scenarios were considered: less frequent injections (mean [SD], 8.2 [1.6] injections annually) and more frequent injections (mean [range], 10.5 [6.8-13.1] injections annually). The 2 treatment innovation scenarios, improved adherence and best case, had the same vision outcomes as the current treatment scenarios had but included more patients treated from higher initiation and lower discontinuation. Results: The study population included 168 820 patients aged 65 years at the time of diagnosis with wAMD. The underlying clinical trials that were used to parameterize the model did not stratify visual acuity outcomes or treatment frequency by sex; therefore, the model parameters could not be stratified by sex. The current treatment scenario of less frequent injections generated $1.1 billion for the full population in year 1 and $5.1 billion in year 3, whereas the scenario of more frequent injections generated $1.6 billion (year 1) and $8.2 billion (year 3). Three-year benefits ranged from $7.3 billion to $11.4 billion in the improved adherence scenario and from $9.7 billion to $15.0 billion if 100% of the patients initiated anti-VEGF treatment and the discontinuation rates were 6% per year or equivalent to clinical trial discontinuation (best-case scenario). Societal value (patient benefits net of treatment cost) ranged from $0.9 billion to $3.0 billion across 3 years in the current treatment scenarios and from $0.9 billion to $4.3 billion in the treatment innovation scenarios. Conclusions and Relevance: This study's findings suggest that improved vision associated with anti-VEGF treatment may provide economic value to patients and society if the outcomes match published outcomes data used in these analyses; however, future innovations that increase treatment utilization may result in added economic benefit.

An analysis of ranibizumab treatment and visual outcomes in real-world settings: the UNCOVER study.

PURPOSE: To describe intravitreal ranibizumab treatment frequency, clinical monitoring, and visual outcomes (including mean central retinal thickness [CRT] and visual acuity [VA] changes from baseline) in neovascular age-related macular degeneration (nAMD) in real-world settings across three ranibizumab reimbursement scenarios in the Middle East, North Africa, and the Asia-Pacific region. METHODS: Non-interventional multicenter historical cohort study of intravitreal ranibizumab use for nAMD in routine clinical practice between April 2010 and April 2013. Eligible patients were diagnosed with nAMD, received at least one intravitreal ranibizumab injection during the study period, and had been observed for a minimum of 1 year (up to 3 years). Reimbursement scenarios were defined as self-paid, partially-reimbursed, and fully-reimbursed. RESULTS: More than three-fourths (n = 2521) of the analysis population was partially-reimbursed for ranibizumab, while 16.4% (n = 532) was fully-reimbursed, and 5.8% was self-paid (n = 188). The average annual ranibizumab injection frequency was 4.1 injections in the partially-reimbursed, 4.7 in the fully-reimbursed and 2.6 in the self-paid populations. The average clinical monitoring frequency was estimated to be 6.7 visits/year, with similar frequencies observed across reimbursement categories. On average, patients experienced VA reduction of -0.7 letters and a decrease in CRT of -44.4 µm. The greatest mean CRT change was observed in the self-paid group, with -92.6 µm. CONCLUSIONS: UNCOVER included a large, heterogeneous ranibizumab-treated nAMD population in real-world settings. Patients in all reimbursement scenarios attained vision stability on average, indicating control of disease activity.

Challenges Associated with Estimating Utility in Wet Age-Related Macular Degeneration: A Novel Regression Analysis to Capture the Bilateral Nature of the Disease.

INTRODUCTION: The estimation of utility values for the economic evaluation of therapies for wet age-related macular degeneration (AMD) is a particular challenge. Previous economic models in wet AMD have been criticized for failing to capture the bilateral nature of wet AMD by modelling visual acuity (VA) and utility values associated with the better-seeing eye only. METHODS: Here we present a de novo regression analysis using generalized estimating equations (GEE) applied to a previous dataset of time trade-off (TTO)-derived utility values from a sample of the UK population that wore contact lenses to simulate visual deterioration in wet AMD. This analysis allows utility values to be estimated as a function of VA in both the better-seeing eye (BSE) and worse-seeing eye (WSE). RESULTS: VAs in both the BSE and WSE were found to be statistically significant (p < 0.05) when regressed separately. When included without an interaction term, only the coefficient for VA in the BSE was significant (p = 0.04), but when an interaction term between VA in the BSE and WSE was included, only the constant term (mean TTO utility value) was significant, potentially a result of the collinearity between the VA of the two eyes. The lack of both formal model fit statistics from the GEE approach and theoretical knowledge to support the superiority of one model over another make it difficult to select the best model. CONCLUSION: Limitations of this analysis arise from the potential influence of collinearity between the VA of both eyes, and the use of contact lenses to reflect VA states to obtain the original dataset. Whilst further research is required to elicit more accurate utility values for wet AMD, this novel regression analysis provides a possible source of utility values to allow future economic models to capture the quality of life impact of changes in VA in both eyes. FUNDING: Novartis Pharmaceuticals UK Limited.

UK AMD/DR EMR REPORT IX: comparative effectiveness of predominantly as needed (PRN) ranibizumab versus continuous aflibercept in UK clinical practice.

AIMS: To compare the effectiveness of continuous aflibercept versus pro re nata (PRN) ranibizumab therapy for neovascular age-related macular degeneration (nAMD). METHODS: Multicentre, national electronic medical record (EMR) study on treatment naive nAMD eyes undergoing PRN ranibizumab or continuous (fixed or treat and extend (F/TE)) aflibercept from 21 UK hospitals. Anonymised data were extracted, and eyes were matched on age, gender, starting visual acuity (VA) and year of starting treatment. Primary outcome was change in vision at 1 year. RESULTS: 1884 eyes (942 eyes in each group) were included. At year 1, patients on PRN ranibizumab gained 1.6 ETDRS (Early Treatment Diabetic Retinopathy Study) letters (95% CI 0.5 to 2.7, p=0.004), while patients on F/TE aflibercept gained 6.1 letters (95% CI 5.1 to 7.1, p=2.2e-16). Change in vision at 1 year of the F/TE aflibercept group was 4.1 letters higher (95% CI 2.5 to 5.8, p=1.3e-06) compared with the PRN ranibizumab group after adjusting for age, starting VA, gender and year of starting therapy. The F/TE aflibercept group had significantly more injections compared with the PRN ranibizumab group (7.0 vs 5.8, p<2.2e-16), but required less clinic visits than the PRN ranibizumab group (10.8 vs 9.0, p<2.2e-16). Cost-effectiveness analysis showed an incremental cost-effectiveness ratio of 58 047.14 GBP/quality-adjusted life year for continuous aflibercept over PRN ranibizumab. CONCLUSION: Aflibercept achieved greater VA gains at 1 year than ranibizumab. The observed VA differences are small and likely to be related to more frequent treatment with aflibercept, suggesting that ranibizumab should also be delivered by F/TE posology.

Economic Evaluation of a Home-Based Age-Related Macular Degeneration Monitoring System.

Background: Medicare recently approved coverage of home telemonitoring for early detection of incident choroidal neovascularization (CNV) among patients with age-related macular degeneration (AMD), but no economic evaluation has yet assessed its cost-effectiveness and budgetary impact. Objectives: To evaluate a home-based daily visual-field monitoring system using simulation methods and to apply the findings of the Home Monitoring of the Eye study to the US population at high risk for wet-form AMD. Design, Setting, and Participants: In this economic analysis, an evaluation of the potential cost, cost-effectiveness, and government budgetary impact of adoption of a home-based daily visual-field monitoring system among eligible Medicare patients was performed. Effectiveness and visual outcomes data from the Age-Related Eye Disease Study 2 Home Monitoring of the Eye study, treatment data from the Wills Eye Hospital Treat & Extend study, and AMD progression data from the Age-Related Eye Disease Study 1 were used to simulate the long-term effects of telemonitoring patients with CNV in one eye or large drusen and/or pigment abnormalities in both eyes. Univariate and probabilistic sensitivity analysis and an alternative scenario using the Treat & Extend study control group outcomes were used to examine uncertainty in these data and assumptions. Interventions: Home telemonitoring of patients with AMD for early detection of CNV vs usual care. Main Outcomes and Measures: Incremental cost-effectiveness ratio, net present value of lifetime societal costs, and 10-year nominal government expenditures. Result: Telemonitoring of patients with existing unilateral CNV or multiple bilateral risk factors for CNV (large drusen and retinal pigment abnormalities) incurs $907 (95% CI, -$6302 to $2809) in net lifetime societal costs, costs $1312 (95% CI, $222-$2848) per patient during 10 years from the federal government's perspective, and results in an incremental cost-effectiveness ratio of $35 663 (95% CI, cost savings to $235 613) per quality-adjusted life-year gained. Conclusions and Relevance: Home telemonitoring of patients with AMD who are at risk for CNV was cost-effective compared with scheduled examinations alone. Monitoring patients with existing CNV in one eye is cost saving, but monitoring is generally not cost-effective among patients with low risk of CNV, including those with no or few risk factors. With Medicare coverage, monitoring incurs budgetary expenditures for the government but is cost-saving for patients at high risk of AMD. Monitoring could be cost saving to society if monitoring reduced the frequency of scheduled examinations or led to a reduction of one or more injections of ranibizumab.

Simulation Modelling in Ophthalmology: Application to Cost Effectiveness of Ranibizumab and Aflibercept for the Treatment of Wet Age-Related Macular Degeneration in the United Kingdom.

BACKGROUND: Previously developed models in ophthalmology have generally used a Markovian structure. There are a number of limitations with this approach, most notably the ability to base patient outcomes on best-corrected visual acuity (BCVA) in both eyes, which may be overcome using a different modelling structure. Simulation modelling allows for this to be modelled more precisely, and therefore may provide more accurate and relevant estimates of the cost effectiveness of ophthalmology interventions. OBJECTIVE: This study aimed to explore the appropriateness of simulation modelling in ophthalmology, using the disease area of wet age-related macular degeneration (wAMD) as an example. METHODS: A de novo economic model was built using a patient-level simulation, which compared ranibizumab with aflibercept in wAMD. Disease progression was measured using BCVA. Health-related quality of life (HRQoL) was estimated using a regression analysis linking BCVA in each eye to utility. The analysis was from the perspective of the National Health Service in the UK. Five different regression models were explored and were based on BCVA in either one eye or both eyes. RESULTS: The model outputs provide some evidence to support the hypothesis that the analyses using the two-eye models for estimating HRQoL generate a more accurate estimation of incremental quality-adjusted life-years (QALYs) associated with the positive treatment effect for ranibizumab versus aflibercept. Second-order analysis broadly supported these findings, and showed that the variation in incremental costs was slightly lower than in incremental QALYs. The second-order analysis estimated similar incremental costs and a greater overall variation in incremental QALYs than the first-order analysis, suggesting important non-linearities within the model. CONCLUSIONS: This analysis suggests that patient-level simulation models may be well suited to representing the real-world patient pathway in wAMD, particularly when aspects of disease progression cannot be adequately captured using a Markov structure. The benefits of a simulation approach can be demonstrated in the modelling of HRQoL as a function of BCVA in both eyes.

Determining patient preferences in the management of neovascular age-related macular degeneration: a conjoint analysis.

PurposeTo determine the opinions from a patient perspective on relevant variables in the delivery of treatment for neovascular age-related macular degeneration (nAMD).MethodsPilot interviews with patients and doctors were conducted to identify what variables in the provision of a nAMD service were important. This led to the generation of two sets of scenario options. Subsequently 100 patients undergoing active treatment for nAMD in the National Health Service University Hospital, United Kingdom underwent interview assessment. They were asked to rank their preferences for provision of their care with reference to these two sets of scenario options. Using conjoint analysis, percentage preferences, and utility scores for each variable in each scenario design were calculated.ResultsNinety-five patients completed the preference ranking for both scenarios. Eight patients ranked worse vision as preferable to better vision and were excluded on the basis that they had not understood the task. The results of the remaining 87 patients are presented. The most important factor to patients was having good vision, followed by a one-stop service and less frequent follow up. The least important factors were label status of the drug, cost to the health service, and grade of the injector.ConclusionPatients regard good vision and minimal visits to the hospital above the status of injector, label status of drug, or cost to the NHS.

Quality of Life in Patients Suffering from Active Exudative Age-Related Macular Degeneration: The EQUADE Study.

PURPOSE: Age-related macular degeneration (AMD) is the main cause of visual loss in the elderly population. With the use of anti-vascular endothelial growth factor, the visual outcomes of exudative AMD patients have been improved. This study was aimed at assessing the quality of life (QoL) of exudative AMD patients treated with ranibizumab and at determining its drivers in a real-life setting. METHODS: We performed a national, cross-sectional, observational survey based on questionnaires sent to members of French associations relative to AMD between December 2012 and March 2013. Patients suffering from exudative AMD with at least one intravitreal injection of ranibizumab within the last 6 months were included. Demographics, AMD characteristics, visual acuity (VA) and past and ongoing treatments were collected. The 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) was self-administered. A multivariate model was used to identify QoL drivers. RESULTS: 416 questionnaires fulfilled the complete criteria for both QoL and cost analyses. The mean age of exudative AMD patients was 78.0 years and bilateral involvement was reported in 60.4%. The overall mean QoL score was 53.4. Mental health, driving and role difficulties were the most widely affected domains. After bivariate analyses, long-term illness status, worse VA and higher number of unpaid aids were associated with worse QoL, with odds ratios of 2.4, 5.2 and 11.6, respectively. The mean cost per year and per patient was 1,741 EUR. The main components of costs were aids and services and the purchase of visual equipment. CONCLUSIONS: The main predictors of QoL in exudative AMD patients treated with ranibizumab are VA outcomes, home healthcare and social services provided to the patients.

Assessment of Choroidal Topographic Changes by Swept-Source Optical Coherence Tomography After Intravitreal Ranibizumab for Exudative Age-Related Macular Degeneration.

PURPOSE: To investigate choroidal topographic changes by swept-source optical coherence tomography (Swept-OCT) in patients undergoing intravitreal injections of anti-vascular endothelial growth factor (VEGF) for exudative age-related macular degeneration (AMD). DESIGN: Prospective interventional study. METHODS: Consecutive patients with unilateral treatment-naïve exudative AMD were entered into the study over 6 months. Changes in choroidal thickness after intravitreal ranibizumab injections, overall in the macula and in neovascular and non-neovascular areas, from baseline to month 3 (loading phase) and month 6 (pro re nata phase), were investigated by means of Swept-OCT maps. RESULTS: Forty-one eyes of 41 patients (mean age: 79.4 ± 7.3 years) were analyzed. Choroidal thickness at study entry was significantly thicker in the study eyes as compared to fellow eyes (P < .05). Analysis of sectorial choroidal thickness over time in study eyes revealed a significant reduction in both neovascular and non-neovascular areas from baseline to month 3 and month 6 (P < .0001 for all). Central choroidal thickness revealed significant variation between treated and fellow eyes from baseline to month 3 (P = .017) and month 6 (P = .045). The visual gain was significantly higher (P = .02) in patients with a larger choroidal thickness reduction (≥29 µm, n = 11) vs the others (n = 30). CONCLUSIONS: The thinning of the macular choroid (affected or not by choroidal neovascularization), along with the significantly thicker choroid in exudative AMD eyes before treatment initiation compared to fellow eyes, allows the hypothesis that anti-VEGF treatment may favorably influence the choroidal exudation by reducing choroidal vascular hyperpermeability.

Routine versus As-Needed Bevacizumab with 12-Weekly Assessment Intervals for Neovascular Age-Related Macular Degeneration: 92-Week Results of the GMAN Trial.

PURPOSE: To evaluate the efficacy and safety of intravitreal bevacizumab (Avastin; Genentech, South San Francisco, CA) in patients with neovascular age-related macular degeneration (nAMD) using 2 different treatment regimens in which patients were assessed clinically at up to 12-week intervals. DESIGN: Randomized, controlled, noninferiority trial. PARTICIPANTS: A total of 331 patients with nAMD. METHODS: Patients were treated with 1.25 mg intravitreal bevacizumab and followed up to 92 weeks. They were randomized into 2 arms. All patients received 3 loading doses 4 weeks apart and thereafter were assessed every 12 weeks until the end of the study. One arm received a routine treatment at each 12-week assessment, and the other arm was treated at these assessments on an as-needed basis. After the loading doses, patients in either arm who showed signs of disease activity had an additional assessment after 6 weeks and at that visit had top-up treatments on an as-needed basis. MAIN OUTCOME MEASURES: Mean best-corrected visual acuity (BCVA) at 92 weeks. RESULTS: At 92 weeks, patients who had treatments every 12 weeks had superior BCVA to those treated on an as-needed basis every 12 weeks (P = 0.008), with the regular treatment arm gaining a mean BCVA of 5.5 letters and the as-needed treatment arm gaining 0.6 letters. The regular treatment arm of the study showed significantly improved outcomes with respect to 5-, 10-, and 15-letter changes in BCVA from baseline compared with the as-needed treatment arm, as well as superior reading speed. In patients who completed the study, up to but not including week 92, the mean number of treatments was 10.8 for the regular treatment arm and 9.1 for the as-needed treatment arm. CONCLUSIONS: A treatment regimen with regular bevacizumab injections every 12 weeks after loading doses supplemented with as-needed top-up treatments produced a stable improvement in BCVA from baseline. The improvement in BCVA was broadly similar to that obtained in other studies using anti-vascular endothelial growth factor drugs with more frequent assessments and treatments.

Ziv-aflibercept in macular disease.

BACKGROUND/AIMS: Aflibercept is an approved therapy for neovascular age-related macular degeneration (AMD) and diabetic macular oedema (DME). In vitro and in vivo studies did not detect toxicity to the retinal pigment epithelium cells using the approved cancer protein, ziv-aflibercept. Our purpose is to determine if ziv-aflibercept can be used in AMD and DME without ocular toxicity, to test the stability of ziv-aflibercept, and to do a cost analysis. METHODS: Prospectively, consecutive patients with AMD or DME and poor vision underwent one intravitreal injection of 0.05 mL of fresh filtered ziv-aflibercept (1.25 mg). Monitoring of best-corrected visual acuity, intraocular inflammation, cataract progression, and retinal structure by spectral domain optical coherence tomography was done at 1 day and 1 week after injection. Ziv-aflibercept activity over 4 weeks was measured by capturing vascular endothelial growth factor by ELISA. RESULTS: There were no signs of retinal toxicity, intraocular inflammation or change in lens status in four eyes with AMD and two eyes with DME. Visual acuity improved (p=0.05) and central foveal thickness decreased in all patients (p=0.05). Ziv-aflibercept had no loss of anti-VEGF activity when kept at 4°C in polycarbonate syringes over 4 weeks. Similar to bevacizumab, compounded ziv-aflibercept would yield a tremendous saving compared with aflibercept or ranibizumab. CONCLUSIONS: Off-label use of ziv-aflibercept improves visual acuity without ocular toxicity and may offer a cheaper alternative to the same molecule aflibercept. TRIAL REGISTRATION NUMBER: NCT02173873.

Cost comparison of intravitreal aflibercept with bevacizumab and ranibizumab for the treatment of wet age-related macular degeneration.

BACKGROUND AND OBJECTIVE: To test the hypothesis that although intravitreal aflibercept (IVA) is expected to be more expensive, the extra cost of treatment would not result in additional vision gain compared with intravitreal bevacizumab (IVB) for the treatment of wet age-related macular degeneration (AMD). PATIENTS AND METHODS: A retrospective chart review of patients receiving IVB or intravitreal ranibizumab (IVR) who were subsequently changed to IVA for active wet AMD. RESULTS: Thirty-three eyes were included in the study. The mean number of IVB, IVR, and IVA injections per eye over a 6-month period was seven, six, and five, respectively. Visual outcomes were similar in all three groups at the end of the study period. The average drug cost of IVB, IVR, and IVA injections per eye over 6 months was $326, $11,400, and $9,720, respectively. CONCLUSION: Aflibercept may allow a modest extension of the treatment interval, but cost makes IVA an expensive alternative without a visual benefit compared with IVB in patients with active wet AMD.

Visual function assessment in simulated real-life situations in patients with age-related macular degeneration compared to normal subjects.

PURPOSE: To evaluate visual function variations in eyes with age-related macular degeneration (AMD) compared to normal eyes under different light/contrast conditions using a time-dependent visual acuity testing instrument, the Central Vision Analyzer (CVA). METHODS: Overall, 37 AMD eyes and 35 normal eyes were consecutively tested with the CVA after assessing best-corrected visual acuity (BCVA) using ETDRS charts. The CVA established visual thresholds for three mesopic environments (M1 (high contrast), M2 (medium contrast), and M3 (low contrast)) and three backlight-glare environments (G1 (high contrast, equivalent to ETDRS), G2 (medium contrast), and G3 (low contrast)) under timed conditions. Vision drop across environments was calculated, and repeatability of visual scores was determined. RESULTS: BCVA significantly reduced with decreasing contrast in all eyes. M1 scores for BCVA were greater than M2 and M3 (P<0.001); G1 scores were greater than G2 and G3 (P<0.01). BCVA dropped more in AMD eyes than in normal eyes between M1 and M2 (P=0.002) and between M1 and M3 (P=0.003). In AMD eyes, BCVA was better using ETDRS charts compared to G1 (P<0.001). The drop in visual function between ETDRS and G1 was greater in AMD eyes compared to normal eyes (P=0.004). Standard deviations of test-retest ranged from 0.100 to 0.139 logMAR. CONCLUSION: The CVA allowed analysis of the visual complaints that AMD patients experience with different lighting/contrast time-dependent conditions. BCVA changed significantly under different lighting/contrast conditions in all eyes, however, AMD eyes were more affected by contrast reduction than normal eyes. In AMD eyes, timed conditions using the CVA led to worse BCVA compared to non-timed ETDRS charts.

Ultrasound assessment of ocular vascular effects of repeated intravitreal injections of ranibizumab for wet age-related macular degeneration.

PURPOSE: Determine the effect of repeated intravitreal injections of ranibizumab (0.5 mg; 0.05 ml) on retrobulbar blood flow velocities (BFVs) using ultrasound imaging quantification in twenty patients with exudative age-related macular degeneration treated for 6 months. METHODS: Visual acuity (ETDRS), central macular thickness (OCT), peak-systolic, end-diastolic and mean-BFVs in central retinal (CRA), temporal posterior ciliary (TPCA) and ophthalmic (OA) arteries were measured before, 2 days, 3 weeks and 6 months after the first injection. Patients were examined monthly and received 1-5 additional injections depending on ophthalmologic examination results. RESULTS: Six months after the first injection, a significant increase in visual acuity 50.9 ± 25.9 versus 44.4 ± 21.7 (p < 0.01) and decrease in mean central macular thickness 267 ± 74 versus 377 ± 115 µm (p < 0.001) were observed compared to baseline. Although mean-BFVs decreased by 16%±3% in CRA and 20%±5% in TPCA (p < 0.001) 2 days after the first injection, no significant change was seen thereafter. Mean-BFVs in OA decreased by 19%±5% at week 3 (p < 0.001). However, the smallest number of injections (two injections) was associated with the longest time interval between the last injection and month 6 (20 weeks) and with the best return to baseline levels for mean-BFVs in CRA, suggesting that ranibizumab had reversible effects on native retinal vascular supply after its discontinuation. Moreover, a significant correlation between the number of injections and percentage of changes in mean-BFVs in CRA was observed at month 6 (R = 0.74, p < 0.001) unlike TPCA or OA. CONCLUSION: Ranibizumab could impair the native choroidal and retinal vascular networks, but its effect seems reversible after its discontinuation.

The effects of technological advances on outcomes for elderly persons with exudative age-related macular degeneration.

IMPORTANCE Exudative age-related macular degeneration (ARMD) is the major cause of blindness among US elderly. Developing effective therapies for this disease has been difficult. OBJECTIVES To assess the effects of introducing new therapies for treating exudative ARMD on vision of the affected population and other outcomes among Medicare beneficiaries newly diagnosed as having ARMD. DESIGN The study used data from a 5% sample of Medicare claims and enrollment data with a combination of a regression discontinuity design and propensity score matching to assess the effects on the introduction or receipt of new technologies on study outcomes during a 2-year follow-up period. SETTING AND PARTICIPANTS The analysis was based on longitudinal data for the United States, January 1, 1994, to December 31, 2011, for Medicare beneficiaries with fee-for-service coverage. The sample was limited to beneficiaries 68 years or older newly diagnosed as having exudative ARMD as indicated by beneficiaries having no claims with this diagnosis in a 3-year look-back period. EXPOSURES The comparisons with vision outcomes were after vs before the introduction of photodynamic therapy and anti-vascular endothelial growth factor (VEGF) therapy. The comparisons for depression and long-term care facility admission were between beneficiaries newly diagnosed as having exudative ARMD who received photodynamic therapy or anti-VEGF therapy compared with beneficiaries having the diagnosis who received no therapy for this disease. MAIN OUTCOMES AND MEASURES Onset of decrease in vision, vision loss or blindness, depression, and admission to a long-term care facility. RESULTS Among beneficiaries newly diagnosed as having exudative ARMD, the introduction of anti-VEGF therapy reduced vision loss by 41% (95% CI, 52%-68%) and onset of severe vision loss and blindness by 46% (95% CI, 47%-63%). Such beneficiaries who received anti-VEGF therapy and were not admitted to a long-term care facility during the look-back period were 19% (95% CI, 72%-91%) less likely on average to be admitted to a long-term care facility during the follow-up period. CONCLUSIONS AND RELEVANCE This study demonstrates gains in population vision from the introduction of anti-VEGF therapy for patients 68 years or older with an exudative ARMD diagnosis in community-based settings in the United States.

Clinical utilization of anti-VEGF agents and disease monitoring in neovascular age-related macular degeneration.

PURPOSE: To examine bevacizumab and ranibizumab utilization and disease monitoring patterns in patients with neovascular age-related macular degeneration (neovascular AMD) in clinical practice. DESIGN: Retrospective medical claims analysis. METHODS: Patients receiving ≥1 ranibizumab or bevacizumab injection during the 12 months after initial neovascular AMD diagnosis were included. Annual bevacizumab and/or ranibizumab injection utilization was assessed by year of first injection cohorts: 2006 and 2007 (received either agent because of billing code overlap), 2008, 2009, and January-June 2010 (received each agent). Outcome measures were time to first injection relative to neovascular AMD diagnosis and mean numbers of intravitreal injections, ophthalmologist visits, and optical coherence tomography (OCT) and fluorescein angiography (FA) examinations in 12 months. RESULTS: In the 2006 and 2007 cohorts (n = 8767), mean annual numbers of bevacizumab or ranibizumab injections were 4.7 and 5.0, respectively. Over 92% of patients in all cohorts received first treatment within 3 months of neovascular AMD diagnosis. In the 2008-2010 cohorts (n = 10 259), mean annual number of injections remained low (bevacizumab: 4.6, 5.1, and 5.5; ranibizumab: 6.1, 6.6, and 6.9), as did mean numbers of ophthalmologist visits (bevacizumab only) and OCT examinations (both agents), but there was no such trend in FA examinations. CONCLUSIONS: Compared with treatment paradigms validated by clinical trials published at the time, in clinical practice, patients with neovascular AMD received fewer bevacizumab or ranibizumab injections and less-frequent monitoring from 2006 to mid-2011. Factors contributing to this lower injection frequency and visual outcomes associated with reduced utilization need to be researched.