Matthew Byun

Importance: Aflibercept, 8 mg, may have greater therapeutic benefits compared with aflibercept, 2 mg, in patients with neovascular age-related macular degeneration (nAMD), including potentially improved outcomes and decreased treatment burden. Objective: To assess safety and efficacy of aflibercept, 8 mg, in patients with nAMD. Design, Setting, and Participants: The CANDELA trial was a phase 2, randomized, single-masked, open-label, 44-week clinical trial conducted in the US. Treatment-naive patients with active subfoveal choroidal neovascularization secondary to nAMD and a best-corrected visual acuity score of 78 to 24 letters (approximately 20/32 to 20/320) in the study eye were enrolled between November 2019 and November 2021. Interventions: Eligible participants were randomized 1:1 to receive 3 monthly doses of 8 mg (70 μL) or 2 mg (50 μL) of aflibercept followed by doses at weeks 20 and 32. Main Outcomes and Measures: Coprimary end points were the proportion of eyes without fluid (absence of intraretinal and subretinal fluid) in the central subfield at week 16 and safety. Results: All 106 eligible eyes were randomized to receive aflibercept, 8 mg (n = 53), or aflibercept, 2 mg (n = 53). Overall, 66 participants (62.3%) were female. The proportion of eyes without fluid in the central subfield with 8-mg vs 2-mg aflibercept was 50.9% (n = 27) vs 34.0% (n = 18) (difference, 17.0 [95% CI, -1.6 to 35.5] percentage points; P = .08) at week 16 and 39.6% (n = 21) vs 28.3% (n = 15) (difference, 11.3 [95% CI, -6.6 to 29.2] percentage points; nominal P = .22) at week 44. At week 44, mean (SE) change in central retinal thickness was -159.4 (16.4) vs -137.2 (22.8) μm with 8 mg vs 2 mg of aflibercept, respectively (least squares mean difference, -9.5 [95% CI, -51.4 to 32.4]; nominal P = .65) and mean (SE) change in best-corrected visual acuity score was +7.9 (1.5) vs +5.1 (1.5) letters (least squares mean difference, +2.8 [95% CI, -1.4 to +7.0]; nominal P = .20). No differences in safety profiles between the groups were observed. Conclusions and Relevance: Although aflibercept, 8 mg, did not achieve the primary efficacy end point at week 16 at the 2-sided significance level of 5%, the observed trends in anatomic and visual improvements over 44 weeks with aflibercept, 8 mg, indicate potential additional therapeutic benefit over aflibercept, 2 mg. No new safety signals were observed over 44 weeks. These findings support further evaluation of aflibercept, 8 mg, in pivotal trials of exudative retinal diseases including nAMD and diabetic macular edema. Trial Registration: ClinicalTrials.gov Identifier: NCT04126317.

Purpose: This work aimed to assess postoperative outcomes associated with relaxing parafoveal nasal retinotomy for refractory macular hole repair. Methods: This was a retrospective interventional study of patients with persistent or recurrent macular holes following 1 or more standard repair procedures with pars plana vitrectomy and internal limiting membrane peeling. Patients received an additional pars plana vitrectomy and relaxing parafoveal nasal retinotomy, followed by fluid-air and air-gas exchange. Key postoperative outcomes included the achievement of macular hole closure and changes in visual acuity from baseline. Results: Thirteen patients with refractory macular holes were included, with a median age of 65 years (range, 49-90 years). The aperture diameter of the 13 macular holes ranged from 180 to 799 µm (median, 538 µm). Vitrectomy and relaxing parafoveal nasal retinotomy were performed in all 13 eyes, and after a median follow-up of 12 months (range, 3-34 months), anatomical closure was achieved in 12 of 13 eyes (92.3%). Overall, visual acuity (mean ± SE) improved significantly from 1.20 ± 0.15 logMAR (approximate Snellen equivalent, 20/320) at baseline to 0.84 ± 0.11 logMAR (Snellen, ∼ 20/125) during postoperative follow-up ( P < .05). Central and paracentral scotomas were observed in 8 of 11 eyes with postoperative Humphrey visual field 10-2 and/or 24-2 data available. Conclusions: Relaxing parafoveal nasal retinotomy may be an effective method to promote anatomical closure and improve vision outcomes in patients with recalcitrant macular holes.

OBJECTIVE: Patients with diabetic macular oedema (DME) are known to have significantly greater medical treatment burden than patients with non-DME. Frequent injections and office visits can have a substantial impact on patient adherence and quality of life. This analysis assesses the impact of the 0.19 mg fluocinolone acetonide (FAc) implant (or injection) on treatment burden and practice resource utilisation in patients with DME. METHODS AND ANALYSIS: This study is a single-centre retrospective chart review of 30 eyes (23 patients) that received a single FAc implant. Data was collected for a 12-month period pre-injection and post-injection of the FAc implant. Primary outcomes included the frequency of injections and ophthalmology office visits. Secondary outcomes included visual acuity (VA), intraocular pressure (IOP) and central subfield thickness (CSFT). RESULTS: The injection frequency significantly decreased from one injection every 2.6 months pre-injection to one injection every 8.8 months post-injection of the FAc implant (p<0.001). Sixty-three percent of the subjects did not require additional injections post-FAc implant. The mean number of ophthalmology office visits significantly decreased from 12.7 visits pre-FAc to 9.3 visits post-FAc implant (p<0.001). The mean VA (p=0.24) and CSFT (p=0.39) showed a mild numerical improvement that was not statistically significant. Thirty-seven percent of the eyes required additional IOP lowering drops. No eyes required incisional glaucoma surgeries. CONCLUSIONS: The FAc implant significantly decreased the treatment burden and improved practice resource utilisation while maintaining or improving VA and CSFT. IOP events were mostly well-controlled with drops and no eyes required incisional glaucoma surgery.

This is the first study to provide causal evidence on the impact of slot machines on individual consumer bankruptcy filings, using recent econometric techniques designed to identify causality. We exploit very detailed administrative data from Alberta, Canada, on the location of the universe of slot machine locations, and administrative data on the location of universe of individual bankruptcy filers.\nSpecifically, we compare the impacts on neighborhood bankruptcies of a bar or restaurant with a large amount of gambling removing its slot machines, compared to a bar or restaurant with a small amount of gambling removing its slot machines. We exploit our ability to observe the total dollar magnitude of gambling at every bar and restaurant.\nIn order to control for unobservable neighborhood characteristics, we use the spatial difference in difference econometric methodology. This methodology differences out unobservable neighborhood characteristics by comparing bankruptcy filers that are fractions of a kilometer (radii of 0,25 km, 0.5 km and 0.75 km) from the specific bar or restaurant, compared to bankruptcy filers slightly further away (radii of 1.5 km, 2.0 km and 2.5 km).\nWe find that a 1% increase in total dollars gambled in the year prior to the removal of slots from the specific bar or restaurant, causes a 1% to 3% reduction in bankruptcy filers two years after the closure of that slot machine location. These effects are much larger for very close neighbors of the slots location (0.25km) compared to neighbors slightly further away (0.5 km and 0.75 km).