Paul Hahn

Purpose: To evaluate the efficacy of intravitreal (IVT) pegcetacoplan monthly vs avacincaptad pegol monthly (primary analysis), and pegcetacoplan every other month vs avacincaptad pegol monthly (secondary analysis), for geographic atrophy (GA). Methods: Matching-adjusted indirect comparisons were conducted across global phase 3 trials using individual patient data from 2 pegcetacoplan trials (OAKS, NCT03525613; DERBY, NCT03525600) and published aggregate data from the avacincaptad pegol GATHER2 trial (NCT04435366). GATHER2 inclusion and exclusion criteria were applied to the OAKS and DERBY individual patient data. Key baseline variables were balanced using propensity score weighting. GA lesion growth at month 12 was assessed. Results from the matching-adjusted indirect comparisons were combined using meta-analysis. Results: The primary analysis included 103 patients from OAKS and 102 patients from DERBY who met the GATHER2 inclusion and exclusion criteria and 447 patients from GATHER2. In OAKS vs GATHER2, the adjusted difference in GA lesion growth at month 12 between pegcetacoplan monthly and avacincaptad pegol was −0.716 mm ² (95% CI, −1.385 to −0.046; P = .04), statistically favoring pegcetacoplan monthly. In DERBY vs GATHER2, the adjusted difference was −0.234 mm ² (95% CI, −1.354 to 0.885; P = .68), directionally favoring pegcetacoplan monthly. After meta-analysis, the pooled effect for pegcetacoplan monthly vs avacincaptad pegol was −0.589 mm ² (95% CI, −1.164 to −0.014; P = 0.04), statistically favoring pegcetacoplan monthly. A numerically greater reduction in GA lesion growth was observed with pegcetacoplan every other month vs avacincaptad pegol monthly (95% CI, −1.130 to −0.300; P = .25). Conclusions: Matching-adjusted indirect comparisons support a greater reduction in GA growth with pegcetacoplan monthly vs avacincaptad pegol monthly and no significant difference between pegcetacoplan every other month and avacincaptad pegol monthly.

Purpose: To compare the incremental cost-effectiveness of a clinical trial-simulated step-therapy versus real-world treatment for diabetic macular edema (DME). Methods: A theoretical Markov model (follow-up of 2 years and lifetime of 17 years) from the 2025 US societal perspective was used to compare the costs and cost-effectiveness between bevacizumab-first (Protocol AC) and real-world regimens from the Vestrum Health database. The modeling used mean characteristics from a reference case and analyzed low- and high-cost scenarios, total societal costs from formal and informal healthcare and non-healthcare sectors, and differences in utility (visual acuity outcomes) between arms. Results: Protocol AC bevacizumab-first in the reference case was 14% more expensive at 2 years, with a total adjusted societal cost of $69 850 versus $61 304 for real-world treatment. Although visual acuity gains were higher with Protocol AC, the incremental cost-utility ratio (ICUR) was $105 335/quality-adjusted life years (QALY) at 2 years and $151 032/QALY over 17 years, higher than most societal willingness-to-pay thresholds. In the low-cost scenario, Protocol AC was neither cost-saving nor cost-effective at 2 years (ICUR $82 283/QALY) but was cost-effective over 17 years (ICUR $591/QALY). In the high-cost scenario, Protocol AC was not cost-effective at 2 years (ICUR $219 420/QALY) or 17 years (ICUR $207 589/QALY). Probability sensitivity analysis showed that Protocol AC was more expensive in 87% of modeled scenarios and not cost-effective in 76%. Conclusions: Compared with real-world treatment, protocol AC bevacizumab-first treatment for DME was generally not cost-saving. Although better vision outcomes were achieved with bevacizumab-first, the protocol was generally not cost-effective due to greater treatment burdens.

Purpose: To compare the modeled costs of the Protocol AC bevacizumab-first treatment protocol (with a switch to aflibercept for sub-responders) with real-world costs for treatment-naïve patients with diabetic macular edema (DME) over a 2-year period. Methods: Published data from the Diabetic Retinopathy Clinical Research Network (DRCR) Protocol AC bevacizumab-first arm (154 eyes) were used to model 2-year treatment costs. Real-world costs were modeled using data from the Vestrum Health electronic medical records database from a 2016 to 2018 cohort of treatment-naïve eyes with DME (n = 1062) treated with antivascular endothelial growth factor monotherapy. The visual acuity (VA) before treatment in the real-world cohort was matched to Protocol AC. A secondary cost analysis further matched VA gains after treatment in the real-world cohort (n = 346) to Protocol AC. Results: In Protocol AC, the modeled 2-year DME treatment cost in the bevacizumab-first arm was $18,952, with a mean of 16.1 injections over 22.5 visits and 70% of eyes being switched to aflibercept by year 2. (Within 2 years, 57% of injections were bevacizumab and 43% were aflibercept.) Over the same period, the modeled 2-year real-world cost ($11,459) was 40% lower, with a mean of 8.6 injections over 13.8 visits (42% bevacizumab, 45% aflibercept, 13% ranibizumab). Even when matched for baseline VA and a 14-letter VA gain over 2 years, the real-world cost ($15,394) was still 19% lower than the modeled cost in the Protocol AC bevacizumab-first arm. Conclusions: The real-world cost of treating DME over 2 years was significantly lower than the DRCR Protocol AC bevacizumab-first cost. Application of Protocol AC findings into real-world utilization, as with step therapy mandates, should only be considered if the same intensive protocol could be followed. These data suggest that existing real-world costs that reflect physician choice are already significantly lower than protocol-mandated step therapy, even when controlling for similar VA outcomes.

Purpose: To compare physician reimbursements for vitreoretinal surgeries with office-based patient care. Methods: A theoretical model was performed comparing physician work reimbursements for the 10 most common vitreoretinal surgeries with office-based work relative value units (wRVUs) that could have been generated during the same global time period. The reference physician was modeled at 40 patients per 8-hour workday. A lower volume physician and higher volume physician were modeled at 30 patients/day and 50 patients/day, respectively. The reimbursement rates and allocated times for surgery were based on the 2021 values set by Medicare, and the average wRVU per office visit was based on 2021 real-world data from the Vestrum Retinal Healthcare Database. Results: In the reference case, performing any of the 10 most common vitreoretinal surgeries was associated with an opportunity cost with a weighted mean of 49% (range, 40%-68%) relative to lost office productivity. The Centers for Medicare & Medicaid Services (CMS) allocated a weighted mean intraservice time of 73 minutes; however, the reference physician would have to complete the surgery with a weighted average of 5 minutes (range, −31-12 minutes) for surgical wRVUs to equal office-based reimbursements. Performing these 10 surgeries was associated with a 25% opportunity cost even for the lower volume physician and 61% for the higher volume physician. Probability sensitivity analysis with a range of conditions identified opportunity costs from surgery in over 99% of simulated scenarios. Conclusions: Medicare reimbursements for the physician work component of vitreoretinal surgeries represented a significant opportunity cost for the physician relative to office-based patient care of equivalent time, especially for busier physicians. The model did not explore practice overhead and professional liability insurance, which are factored separately by CMS and may influence the opportunity cost depending on utilization. The average threshold surgery times for surgical reimbursements to equal office-based reimbursements may be difficult to achieve.

Purpose: To explore the recent evolution of diabetic macular edema (DME) treatment practice patterns over 5 years among retina specialists in the United States. Methods: This retrospective analysis assessed 306 700 eyes with newly diagnosed DME from the Vestrum Health database between January 2015 and October 2020. The year-over-year and cumulative 5-year distributions of eyes treated with antivascular endothelial growth factor (anti-VEGF) agents, steroids, focal laser, or any combination and those of untreated eyes were calculated. Changes from baseline visual acuity were assessed. Results: Yearly treatment patterns changed significantly from 2015 (n = 18056) to 2020 (n = 11042). The proportion of untreated patients declined over time (32.7% vs 27.7%; P < .001), the use of anti-VEGF monotherapy increased (43.5% vs 61.8%; P < .001), the use of focal laser monotherapy declined (9.7% vs 3.0%; P < .001), and the use of steroid monotherapy remained stable (0.9% vs 0.7%; P = 1.000). Of eyes that maintained follow-up for 5 years (from 2015 to 2020), 16.3% were untreated while 77.5% were treated with anti-VEGF agents (as monotherapy or combination therapy). Vision gains in treated patients remained approximately stable from 2015 (3.6 letters) to 2020 (3.5 letters). Conclusions: From 2015 to 2020, treatment patterns for DME evolved toward greater anti-VEGF monotherapy, stable steroid monotherapy, less laser monotherapy, and fewer untreated eyes.

Purpose: This work compares physician reimbursements for retinal detachment (RD) surgery with office-based patient care. Methods: A theoretical model was constructed from the physician’s perspective for performing a 90-minute uncomplicated RD surgery with its associated perioperative work in the global period (Current Procedural Terminology code 67108) compared with managing 40 patients per 8-hour clinic day in the equivalent time period. The reimbursement rates were based on the 2019 values set by the US Centers for Medicare and Medicaid Services (CMS). Sensitivity analyses were performed varying the perioperative times, clinical productivity, and postoperative visits. Results: The CMS physician reimbursement rate for 67108 surgery was 17.13 work relative value units (wRVUs); meanwhile, the physician in the reference case could have generated 40.89 wRVUs in the office. CMS reimbursement therefore represented a 58% opportunity cost relative to lost office productivity for the physician. A significant disparity was still present even when modeling 30 patients per day. In sensitivity analyses, clinical productivity exceeded surgical compensation in 99% of modeled scenarios. In threshold analyses, the surgeon in the reference case would have to complete the surgery and all immediate perioperative care within 18 minutes to equal the total CMS valuation. Conclusions: CMS reimbursement for RD surgery resulted in a significant opportunity cost for the physician relative to office-based patient care, which was more pronounced for more efficient clinicians in the office. The sensitivity analyses supported the robustness of the model. Reductions in surgery reimbursements relative to office-based patient care might disincentivize busy clinicians.

Purpose: This work analyzes data from a series of surveys developed by the American Society of Retina Specialists (ASRS) that assesses the impact of COVID-19 on physicians, their practices, and their patients. Methods: Five surveys were sent by the ASRS between March and July 2020 to more than 2600 US and international retina specialists. Data and trends from these surveys were analyzed. Results: Most responding retina specialists (87%-95% in the United States and internationally) reported having no known COVID-related symptoms despite reported limitations in personal protective equipment. Clinic volumes globally were drastically reduced in March 2020 with only partial recovery through July 2020, which was slower internationally than in the United States. Practices were compelled to reduce staff and physician employment levels. Most respondents estimated some degree of delay in patient treatment with corresponding declines in vision and/or anatomy that were attributed most frequently to patients’ fears of the pandemic and least frequently to office unavailability. Conclusions: The reported impact of COVID-19 on retina specialists, their practices, and their patients has been substantial. Although retina specialists were quickly resilient in optimizing delivery of patient care in a manner safe for patients and providers, the reduction in clinic volume has been devastating in the United States and internationally, with negative impacts on patient outcomes, reductions in practices’ volume and employment, and risk to practices’ financial health. Future studies will be required to quantify losses associated with these unprecedented and ongoing circumstances caused by the pandemic.

Purpose: This work analyzes a series of eyes with brolucizumab-associated intraocular inflammation (IOI) without retinal vasculitis reported to the American Society of Retina Specialists. Methods: The American Society of Retina Specialists Research and Safety in Therapeutics Committee analyzed clinical characteristics from submitted reports of IOI after brolucizumab. Eyes with retinal vasculitis or that received intraocular antibiotics were excluded. Results: Forty-nine eyes of 45 patients were collected. Mean visual acuity (VA) at baseline was 20/49 (range, 20/20-5/200). Patients presented with IOI a mean of 24 days (range, 3-63 days) after their most recent brolucizumab injection; 61% presented for an unscheduled visit while 39% presented at routine follow-up. Mean VA at IOI presentation was 20/67 (range, 20/20-3/200). The most common symptoms were floaters (78%) and blurry vision (76%). Pain (20%) and redness (16%) were less common; 3 (6%) eyes were asymptomatic. IOI was anterior only in 18%, posterior only in 31%, and both anterior and posterior in 51% of eyes. Treatment included topical steroids alone in 67% of eyes, whereas 10% of eyes received no treatment. Mean VA at last follow-up was 20/56 (range, 20/20-1/200). Three (6%) eyes lost 3 or more lines and 1 (2%) eye lost 6 or more lines. Conclusions: Brolucizumab-associated IOI without retinal vasculitis typically presented with a delayed onset of a few weeks. Often, VA decline was relatively mild. Most symptoms resolved and nearly all had a return-to-baseline VA, but a small percentage of patients had a significant decrease in VA at last follow-up.

Purpose: To analyze a case series of retinal vasculitis reported to the American Society of Retina Specialists (ASRS) following Food and Drug Administration approval of brolucizumab for treatment of neovascular age-related macular degeneration. Methods: The ASRS Research and Safety in Therapeutics Committee analyzed clinical and imaging characteristics from submitted reports of retinal vasculitis after brolucizumab. Results: Retinal vasculitis was reported in 26 eyes of 25 patients (22 [88%] female) after treatment with brolucizumab. Imaging studies were available for 24 of 26 eyes. Most cases (92%) were associated with intraocular inflammation, which presented at a mean of 25 days (range, 3-63 days) after the most recent brolucizumab injection. Mean visual acuity (VA) was 20/52 (range, 20/25-4/200) before the adverse event, 20/151 (range, 20/25-hand motion) at presentation of the adverse event, and 20/243 (range, 20/30-light perception) at last follow-up. Twelve eyes (46%) had a greater than 3-line decrease in VA at final follow-up, and 12 eyes (46%) had a final VA of 20/200 or worse. Analysis of retinal imaging identified vasculopathy that involved retinal arteries (91%), retinal veins (79%), and choroidal vessels (48%). Occlusive disease was apparent on imaging in 83% of eyes. Treatment approaches were varied. Conclusions: Retinal vasculitis has been identified in a series of eyes following brolucizumab. Although a few eyes in this series were asymptomatic or minimally symptomatic, some eyes had significant vision loss. A careful examination for signs of active inflammation prior to brolucizumab injection is recommended. Once vasculopathy is suspected, angiographic imaging may help define the spectrum of involvement. Optimal treatment strategies remain unknown.

The implant is composed of an extraocular component, namely, an electronics case and implant coil, as well as an intraocular component involving a 60-electrode array that is tacked over the macula (figure 1). The extraocular and intraocular components are connected by a trans-scleral silicone-coated polyamide electrode cable, and the implantation procedure involves a 5.2 mm pars plana sclerotomy incision to insert the electrode array and the electrode cable into the eye. The sclerotomy is then sutured around the cable and covered by an allograft or autograft material.5