Faculty Bibliography

Importance/UNASSIGNED:Incidence of conversion to neovascular age-related macular degeneration (nAMD) in untreated fellow eyes of patients who are treated for nAMD in 1 eye with anti-vascular endothelial growth factor agents provides important prognostic information to clinically manage patients. Objective/UNASSIGNED:To investigate the association of treatment assignment (intravitreal aflibercept vs ranibizumab) and baseline characteristics with fellow eye conversion to nAMD in the VEGF (Vascular Endothelial Growth Factor) Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) studies. Design, Setting, and Participants/UNASSIGNED:This post hoc analysis of the VIEW 1 and VIEW 2 studies (randomized, double-masked, active-controlled, multicenter, 96-week, phase 3 trials comparing the efficacy and safety of intravitreal aflibercept in 2457 patients with treatment-naive eyes with nAMD) analyzed a subgroup of participants treated for nAMD in 1 eye who had untreated fellow eyes without neovascularization at baseline. All participants in the VIEW studies were included in 1 of 4 groups: ranibizumab, 0.5 mg, every 4 weeks; aflibercept, 2 mg, every 4 weeks; aflibercept, 0.5 mg, every 4 weeks; or aflibercept, 2 mg, every 8 weeks after 3 injections at 4-week intervals. Data collection in the VIEW studies occurred from July 2007 to August 2011; the data analysis presented in this report took place from April 2016 to November 2018. Interventions/UNASSIGNED:Patients received no treatment in the fellow eyes unless after conversion to nAMD, when any treatment approved by heath authorities was given per the investigators' discretion. Main Outcomes and Measures/UNASSIGNED:Incidence of conversion to nAMD in patients with untreated fellow eyes that had not had clinical signs of neovascularization at baseline. Results/UNASSIGNED:A total of 1561 participants were included in this analysis. At 96 weeks, 375 patients (24.0%) experienced cases of conversion to neovascular disease in the fellow eye, including 107 of the 399 individuals who received ranibizumab, 0.5 mg, every 4 weeks; 93 of the 387 individuals who received aflibercept, 2 mg, every 4 weeks; 84 of the 387 individuals who received aflibercept, 0.5 mg, every 4 weeks; and 91 of the 388 individuals who received aflibercept, 2 mg, every 8 weeks after 3 doses at 4-week intervals. The rates were 18.1, 16.2, 14.7, and 16.0 per 100 patient-years at risk at week 96, respectively. On multivariate analysis, fellow eye conversion was associated with increasing patient age (per 10 years) at baseline (hazard ratio [HR], 1.20 [95% CI, 1.05-1.36]), female sex (HR, 1.32 [95% CI, 1.06-1.63]), intraretinal fluid in the study eye at baseline (HR, 1.28 [95% CI, 1.02-1.61]), and increasing choroidal neovascularization lesion size (per 10 mm2) in the study eye at baseline (HR, 1.29 [95% CI, 1.06-1.57]). Rates of fellow eye conversion were similar with either of the treatments. Conclusions and Relevance/UNASSIGNED:In this secondary analysis of randomized clinical trial data, patients with active nAMD in 1 eye appeared to have a high risk for fellow eye conversion. Such patients should be monitored closely.

Importance/UNASSIGNED:Health care prices may drive differences in health care costs across high-income nations. Adalimumab, ranibizumab, and aflibercept are high-cost medications in the United States and Australia. A comparison of their prices over time may elucidate how ophthalmic medication prices contribute to health care costs. Objective/UNASSIGNED:To compare changes in the prices of adalimumab, ranibizumab, and aflibercept in the United States and Australia, the highest and lowest spenders on health care, respectively, among high-income nations. Design, Setting, and Participants/UNASSIGNED:This retrospective price comparison study examined prices paid by government entities in the United States (Medicare) and Australia (Pharmaceuticals and Benefits Scheme). The analysis and data collection were conducted from March 28 to May 4, 2018, in accordance with guidelines set by the International Society for Pharmacoeconomics and Outcomes Research Task Force on Good Research Practices and prior published studies. No human participants or related data were included in this study. Exposures/UNASSIGNED:The change in mean prices of adalimumab, ranibizumab, and aflibercept in the United States and Australia. Main Outcomes and Measures/UNASSIGNED:Initial, final, and change in medication price annually from 2013 to 2017 in inflation-adjusted 2017 US dollars. Results/UNASSIGNED:The mean prices (US dollar prices unadjusted for inflation) in 2013 and 2017 in the United States were $1114 ($1053) and $1818 ($1818), respectively, for adalimumab; $2102 ($1988) and $1904 ($1904), respectively, for ranibizumab; and $2074 ($1961) and $1956 ($1956), respectively, for aflibercept. The mean (Australian dollar prices unadjusted for inflation) 2013 and 2017 prices in Australia were $1854 (A $1797) and $1206 (A $1574), respectively, for adalimumab; $2157 (A $2090) and $972 (A $1268), respectively, for ranibizumab; and $2030 ($1967) and $996 ($1300), respectively, for aflibercept. The estimated annual change in price for adalimumab was +12.8% (95% CI, 9.1%-16.5%) in the United States compared with -11.1% (95% CI, -15.0% to -7.1%) in Australia, a difference of 23.9% per year (95% CI, 19.7%-28.0%; P < .001). The annual change in price for ranibizumab was -2.6% (95% CI, -3.9% to -1.3%) in the United States compared with -18.5% (95% CI, -29.3% to -7.8%) in Australia, a difference of 15.9% per year (95% CI, 7.6%-24.2%; P = .003). The annual change in price for aflibercept was -1.5% (95% CI, -2.2% to -0.7%) in the United States compared with -16.9% (95% CI, -25.1% to -8.6%) in Australia, a difference of 15.4% (95% CI, 9.1%-21.8%; P = .001). Conclusions and Relevance/UNASSIGNED:Results of this study indicate that the prices of adalimumab, ranibizumab, and aflibercept significantly decreased during the past 5 years in Australia compared with the United States. These data do not indicate why these differences are noted or what actions might affect future pricing in either country.

BACKGROUND:Teleophthalmology is an evidence-based method for diabetic eye screening. It is unclear whether the type of eye care provider performing teleophthalmology interpretation produces significant variability. INTRODUCTION/BACKGROUND:We assessed grading variability between an optometrist, general ophthalmologist, and retinal specialist using images from an urban, diabetic retinopathy teleophthalmology program. METHODS:) were used to assess variability. RESULTS: = 0.50-0.90). DISCUSSION/CONCLUSIONS:Inclusion of multiple types of eye care providers as teleophthalmology readers is unlikely to produce significant variability in the assessment of diabetic retinopathy among high-quality images. Greater variability was found regarding image gradability, nondiabetic eye pathology, and recommended clinical referral times. CONCLUSIONS:Our results suggest that more extensive training and uniform referral standards are needed to improve consensus on image gradability, referable nondiabetic eye pathology, and recommended clinical referral times.

PURPOSE/OBJECTIVE:A comparison of anti-vascular endothelial growth factor (anti-VEGF) medication use across multiple countries. CLINICAL RELEVANCE/CONCLUSIONS:Anti-VEGF medication use is now considered first-line treatment for numerous retinal diseases globally. Exploring medication choices, costs within each healthcare system, policy challenges, emerging treatments, and patient access all provide insight into a newly recognized and major public health issue. METHODS:All data presented in this review are available through the published English literature in PubMed, non-peer-reviewed trade publications, and reported surveys. The following search terms were used: anti-VEGF OR bevacizumab OR ranibizumab OR aflibercept OR pegaptanib OR conbercept AND trends OR survey OR cost OR patterns OR preference. Countries with large populations and available data included the United States, United Kingdom, China, India, Korea, Singapore, and Australia. Population and economic statistics were obtained from published reports from the World Bank, World Health Organization, and Commonwealth Fund. RESULTS:Anti-VEGF medication use and costs are significant aspects of patient and healthcare system expenditures in each nation and may have an especially large potential economic burden in India and China. Bevacizumab use comprises the majority of anti-VEGF medication use in the United States and Singapore, although aflibercept use is growing rapidly. Paradoxically, data demonstrate that there is a significant trend in medication choice toward ranibizumab and aflibercept among practice settings outside of the United States, such as the United Kingdom, China, South Korea, and Australia. The price of anti-VEGF medications ranged from US $30 (ziv-aflibercept) to US $1950 (ranibizumab and aflibercept). Ranibizumab's price ranged from US $240 in India to US $1950 in the United States. Conbercept in China costs approximately US $1150 per dose. CONCLUSIONS:Outside of the United States, many nations are using a majority of more expensive anti-VEGF medications, which may lead to increased costs and decreased access. Increasing the availability of safely compounded anti-VEGF medications will likely improve access, create patient/provider choice, and decrease relative healthcare costs for the growing burden of retinal diseases globally.

PURPOSE/OBJECTIVE:To investigate the association between choroidal caverns, choroidal vascular hyperpermeability (CVH), and pachyvessels in eyes with pachychoroid disease. METHODS:This was a retrospective review of swept-source optical coherence tomography and indocyanine green angiography imaging performed on eyes with pachychoroid disease. RESULTS:Imaging from 21 eyes with pachychoroid disease entities (8 eyes with pachychoroid pigment epitheliopathy, 11 eyes with central serous chorioretinopathy, and 3 eyes with pachychoroid neovasculopathy) from 11 patients (mean 49.5 years, male/female: 10/1, all white) was available for review. In all study eyes, pachyvessels traversed the areas of CVH visible in mid- and late-phase indocyanine green angiography. A total of 504 choroidal caverns were identified in 11 study eyes (52%). Of the 504 choroidal caverns, 445 (88%) were seen within the areas of CVH compared with 59 (12%), which were detected outside the areas of CVH (P < 0.001). Eyes with multiple caverns had an increased choroidal thickness when compared with eyes with ≤1 cavern (P < 0.001). CONCLUSION/CONCLUSIONS:Choroidal caverns, found primarily in the areas of indocyanine green angiography CVH traversed by pachyvessels, were detected in 52% of eyes with pachychoroid disease. The presence of choroidal caverns in these cases may indicate a loss of normal choroidal architecture associated with dilated Haller layer veins and increased choroidal thickness.