Costs of Managing Diabetic Macular Edema With Good Visual Acuity With Aflibercept, Laser, or Observation: DRCR Retina Network Protocol V.

PURPOSE: Because eyes with center-involved diabetic macular edema (CI-DME) and good baseline visual acuity (VA) showed no difference in VA loss when managed initially with observation, laser, or aflibercept, understanding the estimated costs of these strategies to the US population is relevant for health care planning. DESIGN: Preplanned cost analysis from a randomized controlled trial (DRCR Retina Network Protocol V). METHODS: Total costs for managing participants with CI-DME and good baseline VA assigned to aflibercept (n = 226), laser (n = 240), or observation (n = 236) during the 2-year multicenter trial were calculated. Observation or laser groups initiated aflibercept if VA decreased. The aflibercept group received injections up to every 4 weeks. Using epidemiological data and extrapolating costs, 10-year costs of care for all persons with CI-DME and good baseline VA throughout the United States were caluclated. RESULTS: Assuming that all patients in the United States with CI-DME and good baseline VA received aflibercept initially, 10-year costs were projected to be $28.80 billion compared with $14.42 billion if initially receiving laser treatment or $15.70 billion if initially observed, with aflibercept added if VA worsened in the laser or observation arms. CONCLUSIONS: Similar VA outcomes on average are obtained by initially managing CI-DME and good baseline VA with laser or observation strategies instead of immediately using aflibercept. Although any 1 of these 3 strategies might be warranted depending on an individual's specific circumstances, on a societal level, cost savings might be achieved with these first 2 approaches.

Fellowship Match Outcomes in the U.S. From 2010 to 2017: Analysis of San Francisco Match.

PURPOSE: To describe applicant characteristics and outcomes associated with the ophthalmology fellowship match. DESIGN: Retrospective case-control study. METHODS: This study took place in San Francisco and matched data for ophthalmology fellowship applicants in the USA. The study population was registrants for the 2010-2017 ophthalmology fellowship match cycles. The match rate took place during the 8-year study period. Applicant characteristics were stratified by match status and factors associated with matching to ophthalmology fellowship positions. RESULTS: Between 2010 and 2017, most applicants (2,558/3,471; 73.7%) were matched into ophthalmology fellowship programs. No difference over time in the proportion of applicants that matched for fellowship was identified (P = .41). On average, ophthalmology residents who were matched into fellowships had higher step 1 (difference: 9; 99% confidence interval [CI]: 6.8-10.9; P < .001), step 2 (difference: 9.5; 99% CI: 7-12; P < .001), and step 3 (difference: 7.4; 99% CI: 5-9.7; P <.001) scores than those who did not match. Applicants who matched also had a greater number of application distributions (difference: 9.6; 99% CI: 7.9-11.2; P < .001), and ranked programs on the match list (difference: 6.2; 99% CI: 5.8-6.7; P < .001). Among applicants who matched, 15% matched at the same institute, 29% matched in the same state, and 45% matched in the same region. On multivariable analysis, factors associated with an increased likelihood of matching into an ophthalmology fellowship program included graduates from the US versus graduates from non-US residency programs (odds ratio [OR]: 2.09; 99% CI: 1.27-3.44; P <.001), increasing percentage of applications ranked (number of ranked programs and/or number of applications distributed) (OR: 1.02; 99% CI: 1.02-1.03; P < .001) as well as having ranked more programs (OR: 1.24; 99% CI: 1.17-1.31; P < .001). Medical graduate status outside of the US (OR: 0.58; 99% CI: 0.36-0.93; P < .001) was associated with decreased odds of matching for fellowship. CONCLUSIONS: From 2010 to 2017, approximately three-quarters of residents applying for an ophthalmology fellowship position matched. Factors associated with increased likelihood of matching included the applicant's graduating from a U.S. residency, graduating from a U.S. medical school, ranking more programs, and having a higher percentage of applications ranked (number of programs ranked by applicant and/or number of applications distributed). The information gained from this study may help applicants as they consider applying to fellowship programs.

Assessment of the DRCR Retina Network Approach to Management With Initial Observation for Eyes With Center-Involved Diabetic Macular Edema and Good Visual Acuity: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Among eyes with center-involved diabetic macular edema (CI-DME) and good visual acuity (VA), randomized clinical trial results showed no difference in VA loss between initial observation plus aflibercept only if VA decreased, initial focal/grid laser plus aflibercept only if VA decreased, or prompt aflibercept. Understanding the initial observation approach is relevant to patient management. Objective: To assess the DRCR Retina Network protocol-defined approach and outcomes of initial observation with aflibercept only if VA worsened. Design, Setting, and Participants: This was a post hoc secondary analyses of a randomized clinical trial of the DRCR Retina Network Protocol V that included 91 US and Canadian sites from November 2013 to September 2018. Participants were adults (n = 236) with type 1 or 2 diabetes, 1 study eye with CI-DME, and VA letter score at least 79 (Snellen equivalent, 20/25 or better) assigned to initial observation. Data were analyzed from March 2019 to November 2019. Interventions: Initial observation and follow-up with aflibercept only for VA loss of at least 10 letters from baseline at 1 visit or 5 to 9 letters at 2 consecutive visits. Follow-up occurred at 8 weeks and then every 16 weeks unless VA or optical coherence tomography central subfield thickness worsened. Main Outcomes and Measures: Whether individuals received aflibercept. Results: Among 236 eyes in 236 individuals (149 [63%] male; median age, 60 years [interquartile range, 53-67 years]) randomly assigned to initial observation, 80 (34%) were treated with aflibercept during 2 years of follow-up. At 2 years, the median VA letter score was 86.0 (interquartile range, 89.0-81.0; median Snellen equivalent, 20/20 [20/16-20/25]). Receipt of aflibercept was more likely in eyes with baseline central subfield thickness at least 300 µm (Zeiss-Stratus equivalent) vs less than 300 µm (45% vs 26%; hazard ratio [HR], 1.98 [95% CI, 1.26-3.13], continuous P = .005), moderately severe nonproliferative diabetic retinopathy (Early Treatment Diabetic Retinopathy Study retinopathy severity level 47) and above vs moderate nonproliferative diabetic retinopathy (retinopathy severity level 43) and below (51% vs 27%; HR, 2.22 [95% CI, 1.42-3.47], ordinal P < .001), and among participants whose nonstudy eye received DME treatment within 4 months of randomization vs not (52% vs 25%; HR, 2.55 [95% CI, 1.64-3.99], P < .001). Conclusions and Relevance: Most eyes managed with initial observation plus aflibercept only if VA worsened maintained good vision at 2 years and did not require aflibercept for VA loss. However, the eyes in the trial were approximately twice as likely to receive aflibercept for VA loss if they had greater baseline central subfield thickness, worse diabetic retinopathy severity level, or a nonstudy eye receiving treatment for DME. Trial Registration: ClinicalTrials.gov Identifier: NCT01909791.

Five-Year Cost-effectiveness of Intravitreous Ranibizumab Therapy vs Panretinal Photocoagulation for Treating Proliferative Diabetic Retinopathy: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The DRCR Retina Network Protocol S randomized clinical trial suggested that the mean visual acuity of eyes with proliferative diabetic retinopathy (PDR) treated with ranibizumab is not worse at 5 years than that of eyes treated with panretinal photocoagulation (PRP). Moreover, the ranibizumab group had fewer new cases of diabetic macular edema (DME) with vision loss or vitrectomy but had 4 times the number of injections and 3 times the number of visits. Although 2-year cost-effectiveness results of Protocol S were previously identified, incorporating 5-year data from Protocol S could alter the longer-term cost-effectiveness of the treatment strategies from the perspective of the health care system. Objective: To evaluate 5- and 10-year cost-effectiveness of therapy with ranibizumab, 0.5 mg, compared with PRP for treating PDR. Design, Setting, and Participants: A preplanned secondary analysis of the Protocol S randomized clinical trial using efficacy, safety, and resource utilization data through 5 years of follow-up for 213 adults diagnosed with PDR and simulating results through 10 years. Interventions: Intravitreous ranibizumab, 0.5 mg, at baseline and as frequently as every 4 weeks based on a structured retreatment protocol vs PRP at baseline for PDR; eyes in both groups could receive ranibizumab for concomitant DME with vision loss. Main Outcomes and Measures: Incremental cost-effectiveness ratios (ICERs) of ranibizumab therapy compared with PRP were evaluated for those with and without center-involved DME (CI-DME) and vision loss (Snellen equivalent, 20/32 or worse) at baseline. Results: The study included 213 adults with a mean (SD) age of 53 (12) years, of whom 92 (43%) were women and 155 (73%) were white. The ICER of the ranibizumab group compared with PRP for patients without CI-DME at baseline was $582 268 per quality-adjusted life-year (QALY) at 5 years and $742 202/QALY at 10 years. For patients with baseline CI-DME, ICERs were $65 576/QALY at 5 years and $63 930/QALY at 10 years. Conclusions and Relevance: This study suggests that during 5 to 10 years of treatment, ranibizumab, 0.5 mg, as given in the studied trial compared with PRP may be within the frequently cited range considered cost-effective in the United States for eyes presenting with PDR and vision-impairing CI-DME, but not for those with PDR but without vision-impairing CI-DME. Substantial reductions in anti-vascular endothelial growth factor cost may make the ranibizumab therapy cost-effective within this range even for patients without baseline CI-DME. Trial Registration: ClinicalTrials.gov identifier: NCT01489189.

Assessment of Deep Generative Models for High-Resolution Synthetic Retinal Image Generation of Age-Related Macular Degeneration.

Importance: Deep learning (DL) used for discriminative tasks in ophthalmology, such as diagnosing diabetic retinopathy or age-related macular degeneration (AMD), requires large image data sets graded by human experts to train deep convolutional neural networks (DCNNs). In contrast, generative DL techniques could synthesize large new data sets of artificial retina images with different stages of AMD. Such images could enhance existing data sets of common and rare ophthalmic diseases without concern for personally identifying information to assist medical education of students, residents, and retinal specialists, as well as for training new DL diagnostic models for which extensive data sets from large clinical trials of expertly graded images may not exist. Objective: To develop DL techniques for synthesizing high-resolution realistic fundus images serving as proxy data sets for use by retinal specialists and DL machines. Design, Setting, and Participants: Generative adversarial networks were trained on 133 821 color fundus images from 4613 study participants from the Age-Related Eye Disease Study (AREDS), generating synthetic fundus images with and without AMD. We compared retinal specialists' ability to diagnose AMD on both real and synthetic images, asking them to assess image gradability and testing their ability to discern real from synthetic images. The performance of AMD diagnostic DCNNs (referable vs not referable AMD) trained on either all-real vs all-synthetic data sets was compared. Main Outcomes and Measures: Accuracy of 2 retinal specialists (T.Y.A.L. and K.D.P.) for diagnosing and distinguishing AMD on real vs synthetic images and diagnostic performance (area under the curve) of DL algorithms trained on synthetic vs real images. Results: The diagnostic accuracy of 2 retinal specialists on real vs synthetic images was similar. The accuracy of diagnosis as referable vs nonreferable AMD compared with certified human graders for retinal specialist 1 was 84.54% (error margin, 4.06%) on real images vs 84.12% (error margin, 4.16%) on synthetic images and for retinal specialist 2 was 89.47% (error margin, 3.45%) on real images vs 89.19% (error margin, 3.54%) on synthetic images. Retinal specialists could not distinguish real from synthetic images, with an accuracy of 59.50% (error margin, 3.93%) for retinal specialist 1 and 53.67% (error margin, 3.99%) for retinal specialist 2. The DCNNs trained on real data showed an area under the curve of 0.9706 (error margin, 0.0029), and those trained on synthetic data showed an area under the curve of 0.9235 (error margin, 0.0045). Conclusions and Relevance: Deep learning-synthesized images appeared to be realistic to retinal specialists, and DCNNs achieved diagnostic performance on synthetic data close to that for real images, suggesting that DL generative techniques hold promise for training humans and machines.

Recent clinically relevant highlights from the Diabetic Retinopathy Clinical Research Network.

PURPOSE OF REVIEW: To present some recent clinically relevant results from Diabetic Retinopathy Clinical Research (DRCR) Network trials that may guide management of diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR). RECENT FINDINGS: Among eyes with DME and visual acuity 20/50 or worse, aflibercept, on average, had greater improvement in visual acuity over 2 years compared with bevacizumab or ranibizumab. Aflibercept is associated with higher rates of improvements in diabetic retinopathy severity among eyes with PDR and vision-impairing DME at baseline compared with bevacizumab or ranibizumab. Among eyes with persistent central-involved DME after at least six antivascular endothelial growth factor (anti-VEGF) injections, no difference in mean visual acuity improvement was observed between eyes that received continued ranibizumab and sham injections versus ranibizumab and intravitreous sustained dexamethasone drug-delivery system, especially for phakic eyes. For eyes with PDR, ranibizumab was associated with lower rates of developing PDR-worsening events compared with panretinal photocoagulation, especially among eyes that did not receive ranibizumab for central-involved DME at baseline. Ranibizumab is cost-effective for PDR for eyes with, not without, vision-impairing central-involved DME, highlighting challenges when safety and efficacy results are at odds with cost-effectiveness results. SUMMARY: Aflibercept for DME, in certain circumstances, is more likely to have superior visual acuity and anatomical outcomes compared with bevacizumab or ranibizumab. No vision benefits are apparent, especially for phakic eyes, by adding intravitreous corticosteroids for persistent DME following anti-VEGF injections.