Real-world visual acuity outcomes for patients with naïve neovascular age-related macular degeneration treated with aflibercept, ranibizumab, or bevacizumab in the Republic of Korea.

BACKGROUND: To compare the visual outcomes of different anti-vascular endothelial growth factor (VEGF) drugs, including aflibercept, ranibizumab, and bevacizumab, in a real-world setting in Korea. METHODS: We collected data from patients who received monotherapy using one of these three anti-VEGF drugs as naïve treatment after being diagnosed with neovascular age-related macular degeneration. The number of injections and visual acuity (VA) outcomes of each cohort were obtained and pairwise comparisons were performed using propensity score matching. RESULTS: A total of 254 aflibercept, 238 ranibizumab, and 282 bevacizumab treatment-naïve eyes were included. The mean VA change at 3 years for all cohorts combined was -1.8 letters, and the mean number of injections was 9.4. In the direct comparison of the three drugs, the mean change in the VA letter score was +2.0 letters for aflibercept and -11.7 letters for bevacizumab (P < 0.001). The number of aflibercept injections was significantly higher than the number of bevacizumab injections (P = 0.002). The visual outcomes for aflibercept and ranibizumab were +4.7 letters and -1.9 letters, respectively, and comparable results were obtained (P = 0.13). The VA outcomes for ranibizumab and bevacizumab were also not significantly different (P = 0.09). The numbers of injections for aflibercept, ranibizumab, and bevacizumab were 10.8, 6.7, and 8.8, respectively. Significant differences were observed between the injection frequencies comparisons of aflibercept and ranibizumab and ranibizumab and bevacizumab (P < 0.001 and P = 0.002, respectively). CONCLUSIONS: In the Korean clinical medical environment, which included various confounding factors, especially socioeconomic ones, the aflibercept VA outcome was significantly better than that of bevacizumab, and aflibercept injections were the most numerous. These real-world data imply that the drug effect as well as the environment in which the drug can be sufficiently used affected patient final VA scores.

New prefilled syringe aflibercept design. A cause of symptomatic IOP spike after aflibercept PFS?

Objective: To describe ocular hypertension cases after using a new aflibercept prefilled syringe and to assess the main characteristics of these eyes and their possible association with intraocular pressure (IOP) changes. Methods: Case series. We reported all the cases of ocular hypertension following aflibercept prefilled syringes (PFS) treatment in our department between April 2021 and December 2023. Results: A total of 4183 eyes were treated with aflibercept PSF. Thirteen transitory IOP elevations were observed immediately after injection (0.3%). Two eyes had an IOP between 30-35 mmHg, five eyes had an IOP between 36-55 mmHg and three eyes had an IOP > 56 mmHg. The mean IOP was 45.5 mmHg±11.33. Only six eyes needed anterior chamber paracentesis (37.5%). The other patients were treated conservatively (ocular massage and/or IOP-lowering drops). The mean IOP after treatment was 15.71 mmHg±7.20. Visual acuity improved after treatment in all the patients. Discussion: Compared with other injectors, reports have indicated a higher incidence of moderate and severe IOP spikes with aflibercept PSF. The European Medicine Agency (EMA) has associated this significant increase with incorrect syringe handling, leading to higher injection volumes. Although plunger misalignment seems to play a role in the IOP spikes, some other characteristics of this new injector could play a role. Factors such as syringe diameter, plunger alignment, and injection force may contribute to this issue. The reason some authors found no significant differences in IOP elevation after IVI, with aflibercept PFS, could be due to variations in patient characteristics, which may also play an important role in post-IVI pressure changes. Conclusions: Intraocular pressure spikes after aflibercept PFS can be explained by injector characteristics. The PFS of aflibercept has a domed plunger. Incorrect alignment between the base of the plunger and the black dosing line could cause an increase in the injected volume. Furthermore, the wider syringe diameter of aflibercept PFS could imply a larger injection force, increasing the risk of IOP elevation. Patient characteristics, such as previous VPP, axial length, or glaucoma history, may also play a role. Further studies are required to develop an ideal intravitreal syringe.

Efficacy and Safety of Aflibercept and Ranibizumab in the Treatment of Retinopathy of Prematurity.

PURPOSE: To compare the efficacy, recurrence rate, and recurrence interval of intravitreal injection of aflibercept (IVA) and ranibizumab (IVR) in patients with retinopathy of prematurity (ROP). METHODS: This is a single-center retrospective study of neonates hospitalized from January 2018 to March 2023 in the Department of Neonatology of the First Affiliated Hospital of Zhengzhou University who received intravitreal injection of anti-vascular endothelial growth factor owing to type 1 prethreshold ROP, threshold ROP, or aggressive posterior ROP. Clinical data were collected to record the cure, recurrence, number of injections, and side effects of ROP. FINDINGS: A total of 224 neonates (444 eyes) were enrolled in this study, of which 121 (241 eyes) received IVA and 103 (203 eyes) received IVR. There were no significant differences in the general characteristics of infants between the two groups (P > 0.05). The corrected gestational age of the first injection was 37.27 ± 3.07 weeks in the IVA group and 37.20 ± 4.89 weeks in the IVR group (P = 0.582). The recurrence rate was 15.8% in the IVA group and 14.9% in the IVR group (P = 0.841). For relapsed infants, the postmenstrual age (PMA) was 34.89 ± 3.49 weeks in the IVA group and 35.28 ± 4.43 weeks in the IVR group at the first treatment. The PMA was 43.69 ± 4.57 and 40.96 ± 4.98 weeks at the second treatment in the IVA and IVR groups, respectively (P = 0.185). There were two children in the IVA group that required a third treatment, with PMAs of 58.71 and 57.29 weeks at the time of surgery, and one child in the IVR group, with a PMA of 43.14 weeks at the time of injection (P = 0.221). No complications were recorded in either group. IMPLICATIONS: The efficacies of aflibercept and ranibizumab in treating ROP are similar, and the safety of the medications was good. Further research should be conducted in large-scale, prospective clinical trials, providing ophthalmologists with new options for the treatment of ROP.

Successful treatments of idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome-related macular edema and exudation by intravitreal aflibercept injection in a senile patient: A case report.

RATIONALE: The prevalence of idiopathic retinitis, vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome is <1/1,000,000, and it tends to occur in young women. Panretinal photocoagulation, focal laser photocoagulation, peripheral cryopexy, vitrectomy, and corticosteroid therapy are the traditional treatments. We reported a case of a senile patient with IRVAN syndrome who presented with severe exudation in both eyes and macular edema in the left eye, successfully treated by serial intravitreal aflibercept injections. PATIENT CONCERNS: A 77-year-old Taiwanese woman complained of progressive blurred vision in the left eye and ocular examinations revealed a visual acuity of 20/125 in the left eye. DIAGNOSIS: Indirect fundoscopy and fluorescein angiography showed bilateral multiple aneurysms, vasculitis, optic nerve staining, and neovascularizations. In addition, optical coherence tomography demonstrated macular edema with subretinal fluid and exudations in the left eye. INTERVENTIONS: Monthly intravitreal injections of antivascular endothelial growth factor with aflibercept 2.0 mg were administered in the left eye. OUTCOMES: The visual acuity in the left eye improved to 20/50 after 18 months of treatment. Macular edema and subretinal fluid regressed. Furthermore, vessel leakage and optic disc staining also improved. LESSONS: This case is the first to demonstrate successful treatment of IRVAN syndrome-related central macular edema and exudations, in the absence of neovascularization, using a series of intravitreal aflibercept injections as monotherapy.

Aflibercept Biosimilar MYL-1701P vs Reference Aflibercept in Diabetic Macular Edema: The INSIGHT Randomized Clinical Trial.

Importance: Biosimilars may be lower-cost alternatives to originator biologic products, potentially offering expanded access or reduced economic burden, but have not been evaluated with aflibercept in diabetic macular edema (DME). Objective: To compare efficacy and safety of MYL-1701P, an aflibercept biosimilar, with reference aflibercept (Eylea [Regeneron]) in DME. Design, Setting, and Participants: This was a double-masked, randomized clinical trial that included participants at 77 centers across the US, Europe, Japan, and India. Included in the analysis were individuals 18 years and older with type 1 or type 2 diabetes with central DME and best-corrected visual acuity (BCVA) letter score of 73 to 38 in the study eye using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Study data were analyzed from October to December 2021. Interventions: Formulations of MYL-1701P (0.5-mg vial) or reference aflibercept every 4 weeks for 5 consecutive intravitreal injections, followed by every 8 weeks through week 52. Main Outcomes and Measures: The primary outcome was the adjusted difference in least squares mean (SE) change from baseline BCVA letter score at week 8 with an equivalence margin of -3 to +3 letters. Secondary outcomes included change in central subfield thickness (CST), BCVA, number of injections over 52 weeks, incidence of adverse events (AEs), and antidrug antibodies (ADAs). Results: A total of 355 participants (mean [SD] age, 62.2 [9.2] years; 216 male [60.8%]) were randomized to MYL-1701P (179 participants [50.4%]) and aflibercept (176 participants [49.6%]). At week 8, mean (SE) change in BCVA was 6.60 (0.55) letters vs 6.56 (0.55) letters in the MYL-1701P vs aflibercept groups. The adjusted mean difference of 0.04 letters (90% CI, -1.16 to 1.24 letters) met the primary outcome. At week 8, mean (SE) change in CST was -112 (7) µm vs -124 (7) µm in the MYL-1701P vs aflibercept groups (adjusted mean difference, 12 µm; 90% CI, -3 to 26 µm). The incidence of treatment-emergent AEs in the MYL-1701P and aflibercept arms were ocular (30.9% [55 of 178] vs 29.5% [52 of 176]), serious ocular (0.6% [1 of 178] vs 1.1% [2 of 176]), nonocular (65.2% [116 of 178] vs 65.3% [115 of 176]), and serious nonocular (16.9% [30 of 178] vs 11.9% [21 of 176]). The mean (SD) total number of injections was 8.4 (2.1) vs 8.7 (1.8) in the MYL-1701P vs aflibercept groups. The incidence of treatment-induced or treatment-boosted ADAs was 2.8% (5 of 177) vs 5.7% (10 of 176) in the MYL-1701P vs aflibercept arms. Conclusions and Relevance: MYL-1701P demonstrated clinical equivalence in regard to efficacy, with comparable safety and immunogenicity, to reference aflibercept. These findings support use of MLY-1701P as an alternative to reference aflibercept. Trial Registration: ClinicalTrials.gov Identifier: NCT03610646.

[Aflibercept in the clinical routine: the AURIGA study : The 24-month results of the German cohort of treatment-naïve patients with diabetic macular edema receiving intravitreal aflibercept]. / Aflibercept im klinischen Alltag: die AURIGA-Studie : 24-Monats-Ergebnisse der deutschen Kohorte behandlungsnaiver Patienten mit diabetischem Makulaödem unter Therapie mit intravitrealem Aflibercept.

BACKGROUND: AURIGA is the largest prospective real-world study to evaluate intravitreal aflibercept (IVT-AFL) treatment of diabetic macular edema (DME) and macular edema secondary to retinal vein occlusion. This article presents 24-month data from the German cohort of treatment-naïve patients with DME. METHODS: Treatment-naïve patients (≥ 18 years) with DME were treated with IVT-AFL at the discretion of the physician in clinical practice. The primary endpoint was mean change in visual acuity (early treatment diabetic retinopathy, ETDRS, letters) at month 12 compared to baseline. Statistical analyses were descriptive. RESULTS: The analysis included data from 150 DME patients (54.7% male). At months 6, 12 and 24, mean (95% confidence interval) visual acuity gains of 4.6 (2.6; 6.5), 4.0 (2.1; 6.5) and 5.0 (3.0; 6.9) letters from baseline (mean ±SD: 65.0 ± 15.3 letters) and reductions in retinal thickness of 86µm (109; 64µm), 70µm (94; 43µm) and 75µm (103; 47µm) from baseline (mean ±SD: 391 ± 132 µm), respectively, were achieved. At month 24, 54% of patients gained ≥ 5 letters and 22% ≥ 15 letters. Patients received a mean number of 5.0 ± 1.6 injections until month 6, 7.1 ± 3.2 until month 12 and 9.0 ± 5.3 until month 24, 68% of patients received ≥ 5 injections until month 6 and 56% ≥ 7 injections within the first year. The safety profile was consistent with previous studies. DISCUSSION: In the German AURIGA cohort, treatment-naïve DME patients achieved a clinically relevant gain in visual acuity as well as reduction in central retinal thickness following IVT-AFL treatment in clinical practice. From month 6 onwards, improvements were maintained despite a low injection frequency over 24 months. In comparison with previous real-world studies, care of DME patients in clinical practice seems to have improved; however, there is still room for further improvement.

Switch to faricimab after initial treatment with aflibercept in eyes with neovascular age-related macular degeneration.

PURPOSE: To investigate the efficacy and outcomes of switching neovascular age-related macular degeneration (nAMD) patients from aflibercept to faricimab, focusing on visual acuity, retinal fluid management, and treatment intervals. The primary aim was to assess the early outcomes in nAMD patients refractory to aflibercept and explore faricimab's potential as a longer-lasting therapeutic alternative. METHODS: A single-center retrospective study was conducted on 50 refractory nAMD patients at Cleveland Clinic Abu Dhabi from September 2022-May 2023. Patients were switched from aflibercept to faricimab, having met specific criteria for refractory nAMD. The study analyzed best-corrected visual acuity (BCVA), central subfield thickness (CST), and fluid changes post-switch, using Optical Coherence Tomography (OCT). RESULTS: After three faricimab injections, significant reductions in CST were observed, with a notable decrease in retinal fluid. The mean BCVA remained stable throughout the study period. Although there was a decrease in the maximum pigment epithelial detachment (PED) height, it was not statistically significant. Treatment intervals post-switch showed that the majority of patients maintained or extended their treatment intervals, with a significant proportion achieving resolution of intraretinal fluid (IRF) and subretinal fluid (SRF). CONCLUSIONS: Switching to faricimab from aflibercept in refractory nAMD patients led to significant improvements in retinal fluid management and CST, with stable BCVA outcomes. Faricimab presents a promising alternative for patients requiring frequent aflibercept injections, potentially offering a more manageable treatment regimen with extended dosing intervals. This study highlights the need for personalized therapeutic strategies in nAMD treatment, though further research is necessary to optimize treatment switches.

EFFICACY AND SAFETY OF THE PROPOSED BIOSIMILAR AFLIBERCEPT, SDZ-AFL, IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: 52-Week Results From the Phase 3 Mylight Study.

PURPOSE: The Phase 3 Mylight study was designed to confirm clinical equivalence of proposed biosimilar aflibercept (SOK583A1; Sandoz [proposed biosimilar aflibercept, SDZ-AFL]) to its reference biologic (Eylea; Regeneron Pharmaceuticals, Inc; Bayer AG [reference aflibercept, Ref-AFL]). METHOD: Mylight was a prospective, double-masked, 2-arm, parallel Phase 3 study. Participants with neovascular age-related macular degeneration were randomized 1:1 to receive eight injections of SDZ-AFL (n = 244) or Ref-AFL (n = 240) over 48 weeks. The primary endpoint was mean change in best-corrected visual acuity score from baseline to Week 8. Secondary endpoints included anatomical outcomes, best-corrected visual acuity at Weeks 24 and 52, safety, and pharmacokinetics. RESULTS: Similarity in mean change in best-corrected visual acuity score was established between SDZ-AFL (n = 235) and Ref-AFL (n = 226) at Week 8 (difference: -0.3 [90% CI, -1.5 to 1.0]) and Week 52. No clinically meaningful differences occurred between groups in anatomical outcomes. Safety profiles were similar, with comparable incidences of treatment-related adverse events (SDZ-AFL: 2.5%; Ref-AFL: 2.9%). The incidence of anti-drug antibodies was similar between groups. Systemic free aflibercept concentrations 24 hours postdose were low and comparable between SDZ-AFL and Ref-AFL. CONCLUSION: Proposed biosimilar aflibercept matched reference aflibercept in efficacy, safety, and pharmacokinetics in participants with neovascular age-related macular degeneration. Therefore, this Phase 3 study confirmed biosimilarity of SDZ-AFL to Ref-AFL.

PROSPECTIVE TRIAL OF HOME OPTICAL COHERENCE TOMOGRAPHY-GUIDED MANAGEMENT OF TREATMENT EXPERIENCED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION PATIENTS.

PURPOSE: To evaluate the impact of home optical coherence tomography (OCT)-guided patient management on treatment burden and visual outcomes. METHODS: An interventional trial was conducted to compare frequency of treatment and visual acuity for the neovascular age-related macular degeneration patients before and during use of home optical coherence tomography over a period of 6 months. Patient adherence to regular scanning was measured by the number of scans performed per week. The characteristics of episodes of fluid recurrence and classification of typical fluid volume trajectories were performed. RESULTS: Twenty-seven eyes (21 with diagnosis of neovascular age-related macular degeneration and one converted during the study), of 15 patients were monitored for 6 months, scanning at 6.2 times/week per eye and yielding 4,435 scans of which 91.2% were eligible for artificial intelligence-based fluid volume quantification. Total number of monitoring weeks before and during the study were 1,555 and 509. The mean (SD) number of weeks per injection before and during home OCT management were 8.0 (4.7) and 15.3 (8.5) (P = 0.004), respectively. The mean (SD) visual acuity change before and during home OCT-based management was 3.5 (12.0) letters and 0.0 (9.5) letters (P = 0.45), respectively, showing no significant impact on visual acuity. CONCLUSION: For the first time, remote patient monitoring with a home OCT allowed personalized management of neovascular age-related macular degeneration. This study showed significant reduction in treatment burden while maintaining stable visual acuity.

A multicenter, prospective, phase II trial of second-line aflibercept plus FOLFIRI in patients with metastatic colorectal cancer refractory to an anti-EGFR antibody: HGCSG1801.

Aflibercept (AFL) plus FOLFIRI prolongs overall survival (OS) in patients with metastatic colorectal cancer (mCRC). However, there is limited evidence on the efficacy and safety of AFL plus FOLFIRI previously treated with anti-epidermal growth factor receptor (EGFR) agents. Therefore, we conducted a prospective open-label phase II trial evaluating the efficacy and safety of AFL plus FOLFIRI in Japanese patients with mCRC failing a prior oxaliplatin-based chemotherapy plus an anti-EGFR agent. AFL (4 mg/kg iv) followed by FOLFIRI (irinotecan 180 mg/m2, leucovorin 200 mg/m2 iv, bolus 5-fluorouracil [5-FU] 400 mg/m2, and infusional 5-FU 2400 mg/m2/46 h) was given every 2 weeks until progression or unacceptable toxicities. The primary endpoint was progression-free survival (PFS) rate at 6 months. Forty three patients were enrolled between November 2019 and October 2022. The primary endpoint was met: 6-month PFS rate was 58.8% (90% confidence interval [CI], 45.7%-72.0%). Median PFS and OS were 7.3 months (95% CI, 5.5-11.0 months) and 18.8 months (95% CI, 12.9-26.6 months), respectively. The overall response rate was 20.9% (95% CI, 10.0-36.0%) and disease control rate was 88.4% (95% CI, 74.9-96.1%). The main grade ≥3 adverse events included hypertension (62.8%), neutropenia (55.8%), leukopenia (25.6%), febrile neutropenia (11.6%), fatigue (9.3%), anorexia (9.3%), proteinuria (9.3%), and diarrhea (7.0%). No deaths and no new safety signals with a causal relation to the study treatment were observed. This study suggests that AFL plus FOLFIRI shows a high response rate and a manageable safety profile in Japanese patients with mCRC who failed prior oxaliplatin-based chemotherapy plus an anti-EGFR agent.

Two-year Outcomes of Intravitreal Aflibercept Injection for Neovascular Age-related Macular Degeneration with "Observe before Treat-and-Extend" Method.

PURPOSE: To evaluate 2-year outcomes of intravitreal aflibercept injection for neovascular age-related macular degeneration (nAMD) treated with "observe before treat-and-extend (O-TAE)" strategy in the real-world setting. METHODS: This retrospective study included treatment-naive nAMD patients treated with aflibercept using O-TAE regimen and followed up for more than 2 years. Patients were observed bimonthly to check recurrence after three monthly loading injections. In case of recurrence, treatment was resumed using the TAE regimen starting from the fourth injection. In case of nonrecurrence, observation was continued. Best-corrected visual acuity (BCVA), central macular thickness (CMT), number of injections, TAE intervals, and proportion of recurrence after dry-up following three loadings were analyzed. RESULTS: A total of 38 eyes of 34 patients were included. Follow-up period was 37.0 ± 11.0 months. BCVA by logarithm of minimal angle of resolution improved from 0.33 ± 0.29 at baseline to 0.24 ± 0.23 in the first year (p = 0.010) and 0.25 ± 0.22 in the second year (p = 0.054). CMT decreased significantly from 357.43 ± 74.53 µm at baseline to 269.62 ± 48.12 µm in the first year (p < 0.001) and 279.14 ± 54.64 µm in the second year (p < 0.001). Number of injections were 5.11 ± 1.69 in the first year and 3.84 ± 2.39 in the second year. The percentage of eyes with a TAE interval of ≥12 weeks was 37.0% in the first year and 34.4% in the second year. Of the 36 eyes that dried up after three loadings, 28 eyes (77.8%) recurred, and the average period of recurrence was 6.5 months. The remaining eight eyes (22.2%) had no recurrence during the mean follow-up period of 29.7 months. CONCLUSIONS: This study showed that the newly suggested O-TAE strategy can reduce the treatment burden significantly reducing the number of injections while improving BCVA and CMT in the first and second year.

Vitrectomy as an Adjunct to Treat-and-Extend Anti-VEGF Injections for Diabetic Macular Edema: The Vitrectomy in Diabetic Macular Oedema (VIDEO) Randomized Clinical Trial.

Importance: There are reported benefits from vitrectomy for diabetic macular edema (DME); however, data precede anti-vascular endothelial growth therapy (VEGF) therapy, supporting a need to assess the current role of vitrectomy. Objective: To determine rates of recruitment and efficacy outcomes of vitrectomy plus internal limiting membrane (ILM) peeling adjunctive to treat-and-extend (T&E) anti-VEGF injections for diabetic macular edema (DME). Design, Setting, and Participants: This was a single-masked, multicenter randomized clinical trial at 21 sites in the United Kingdom from June 2018 to January 2021, evaluating single eyes of treatment-naive patients with symptomatic vision loss from DME for less than 1 year. Inclusion criteria were best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study letter score greater than 35 (approximate Snellen equivalent, 20/200 or better) and central subfield thickness (CST) greater than 350 µm after 3 monthly intravitreal injections of ranibizumab or aflibercept. Data analysis was performed in July 2023. Interventions: Patients were randomized 1:1 into vitrectomy plus standard care or standard care alone and further stratified into groups with vs without vitreomacular interface abnormality. Both groups received a T&E anti-VEGF injection regimen with aflibercept, 2 mg, or ranibizumab, 0.5 mg. The vitrectomy group additionally underwent pars plana vitrectomy with epiretinal membrane or ILM peel within 1 month of randomization. Main Outcomes and Measures: Rate of recruitment and distance BCVA. Secondary outcome measures were CST, change in BCVA and CST, number of injections, rate of completed follow-up, and withdrawal rate. Results: Over 32 months, 47 of a planned 100 patients were enrolled; 42 (89%; mean [SD] age, 63 [11] years; 26 [62%] male) completed 12-month follow-up visits. Baseline characteristics appeared comparable between the control (n = 23; mean [SD] age, 66 [10] years) and vitrectomy (n = 24; mean [SD] age, 62 [12] years) groups. No difference in 12-month BCVA was noted between groups, with a 12-month median (IQR) BCVA letter score of 73 (65-77) letters (Snellen equivalent, 20/40) in the control group vs 77 (67-81) letters (Snellen equivalent, 20/32) in the vitrectomy group (difference, 4 letters; 95% CI, -8 to 2; P = .24). There was no difference in BCVA change from baseline (median [IQR], -1 [-3 to 2] letters for the control group vs -2 [-8 to 2] letters for the vitrectomy group; difference, 1 letter; 95% CI, -5 to 7; P = .85). No difference was found in CST changes (median [IQR], -94 [-122 to 9] µm for the control group vs -32 [-48 to 25] µm for the vitrectomy group; difference, 62 µm; 95% CI, -110 to 11; P = .11). Conclusions and Relevance: Enrollment goals could not be attained. However, with 47 participants, evidence did not support a clinical benefit of vitrectomy plus ILM peeling as an adjunct to a T&E regimen of anti-VEGF therapy for DME. Trial Registration: isrctn.org Identifier: ISRCTN59902040.

Retinal vasculitis after intravitreal aflibercept 8 mg for neovascular age-related macular degeneration.

PURPOSE: To evaluate short-term outcomes of intravitreal injection of aflibercept 8 mg for neovascular age-related macular degeneration (nAMD). STUDY DESIGN: Retrospective, interventional case series. METHODS: We retrospectively studied 35 eyes of 34 consecutive patients with nAMD, assessing best-corrected visual acuity (BCVA), foveal thickness (FT), and central choroidal thickness (CCT) before and 4 weeks after the initial intravitreal dose of aflibercept 8 mg. The rate of achieving a dry macula and the incidence of intraocular inflammation (IOI) at week 4 were also determined. RESULTS: BCVA showed significant improvement, with significant reductions in FT and CCT 4 weeks after the initial injection of aflibercept 8 mg (all P < 0.01), with a dry macula being achieved in 20 eyes (57.1%). However, 3 eyes (8.6%) developed non-infectious IOI associated with retinal vasculitis, an adverse event not reported previously. The IOI in these eyes was relatively mild and treated with a posterior subtenon injection of triamcinolone acetonide with or without betamethasone eye drops, resulting in amelioration of IOI without any visual loss. CONCLUSIONS: Intravitreal aflibercept 8 mg appears to be effective for improving visual acuity and ameliorating exudative changes in eyes with nAMD. However, special attention should be given to the potential development of IOI associated with retinal vasculitis.

Systemic effects of anti-VEGF intravitreal injection in patients with age-related macular degeneration: A multi-institutional real-world study.

PURPOSE: In individuals aged >50 years, age-related macular degeneration (AMD) is the leading cause of irreversible blindness. Intravitreal injections of antivascular endothelial growth factor (VEGF) agents (bevacizumab, ranibizumab, and aflibercept) show good efficacy and similar incidences of systemic adverse events (SAEs). However, comparative studies between agents are limited. Our study aimed to compare the real-world SAE risks of bevacizumab, ranibizumab, and aflibercept users. METHODS: This retrospective cohort study identified new bevacizumab, ranibizumab, and aflibercept users in a multi-institutional database in Taiwan between 2014 and 2019. Inverse probability of treatment weights (IPTW) with propensity scores was conducted to achieve homogeneity among groups. The Fine and Gray model was utilized to estimate the subdistribution hazard ratio and 95% confidence interval. RESULTS: This study included 701 bevacizumab, 463 ranibizumab, and 984 aflibercept users. After IPTW, all covariates were well-balanced. All three anti-VEGF agents had a low and comparable number per 100 person-years of major adverse cardiac events, heart failure, thromboembolic events, major bleeding, all-cause admission, and all-cause death (all P > 0.05). No significant differences in long-term change of systolic and diastolic blood pressure, low-density lipoprotein, estimated glomerular filtration rate, and alanine transaminase (all P for interaction > 0.05) were observed among groups. CONCLUSION: Bevacizumab, ranibizumab, and aflibercept had a good systemic safety profile in this study. All groups showed a low and similar SAE risk and no differences in their long-term change of laboratory data. Therefore, these anti-VEGF agents could be prescribed safely to patients with AMD.

One-Year Functional and Morphological Prognosis After Intravitreal Injection Treatments According to Different Morphological Patterns of Diabetic Macular Edema in Real-Life: MARMASIA Study Group Report No.13.

PURPOSE: To evaluate the responses of different optical coherence tomography (OCT) patterns of diabetic macular edema (DME) to intravitreal injection therapy. METHODS: In this retrospective, comparative, and multicenter study, patients who had previously untreated DME, who received intravitreal ranibizumab (IVR) or aflibercept (IVA) and/or steroid treatment with the pro re nata (PRN) treatment regimen after a 3-month loading dose, and had a 12-month follow-up in the MARMASIA Study Group were included. Morphological patterns of DME were divided into four groups based on OCT features diffuse/spongious edema (Group 1), cystoid edema (Group 2), diffuse/spongious edema+subretinal fluid (SRF) (Group 3), and cystoid edema+SRF (Group 4). Changes in central macular thickness (CMT) and best-corrected visual acuity (BCVA) at months 3, 6, and 12, and the number of injections at month 12 were compared between the DME groups. RESULTS: 455 eyes of 299 patients were included in the study. The mean baseline BCVAs [Logarithm of the Minimum Angle of Resolution (logMAR)] in groups 1, 2, 3, and 4 were 0.54 ± 0.24, 0.52 ± 0.25, 0.55 ± 0.23, and 0.57 ± 0.27, respectively. There was no significant difference between the baseline mean BCVAs between the groups (p = .35). The mean BCVAs were significantly improved to 0,47 ± 0,33 in group 1, 0,42 ± 0,33 in group 2, 0,47 ± 0,31 in group 3, and 0,45 ± 0,43 at month 12. There was no significant difference between the groups in terms of BCVA change at month 12 (p = .71). The mean baseline CMTs in groups 1, 2, 3, and 4 were 387,19 ± 128,19, 447,02 ± 132,39, 449,12 ± 109,24, and 544,19 ± 178,61, respectively. At baseline, the mean CMT was significantly higher in Group 4 than in the other groups (p = .000). The mean CMTs were significantly decreased to 325,16 ± 97,55, 334,94 ± 115,99, 324,33 ± 79,20, and 332,08 ± 150,40 in four groups at month 12 respectively (p > .05). The groups had no significant difference in mean CMT at month 12 (p = .835). The change in CMT was significantly higher in Group 4 than in the other groups at month 12 (p = .000). The mean number of intravitreal anti-VEGF injections at month 12 was 4.51 ± 1.57 in Group 1, 4.63 ± 1.54 in Group 2, 4.88 ± 1.38 in Group 3, and 5.07 ± 1.49 in Group 4. The mean number of anti-VEGF injections in Group 1 and Group 2 was significantly lower than in Group 4 (p = 0,014 and p = 0,017). CONCLUSIONS: In real life, there was no significant difference between the DME groups in terms of visual improvement at month 12. However, better anatomical improvement was achieved in Group 4 than in the other DME groups.

Macular Degeneration Drug Prescribing Patterns After Step Therapy Introduction in Medicare Advantage.

Importance: In Medicare Advantage (MA), step therapy for physician-administered drugs is an approach to lowering drug spending. The impact of step therapy in MA on prescribing behavior and the magnitude of any changes has not been analyzed. Objective: To evaluate the impact of step therapy on macular degeneration drug prescribing patterns for 3 large MA insurers. Design, Setting, and Participants: This was a retrospective encounter-based analysis using 20% nationally representative MA outpatient and carrier encounter records for 2017 to 2019. Participants were MA beneficiaries who were 65 years or older and had received a macular degeneration drug administration. Macular degeneration drug administrations for beneficiaries of MA Aetna, Humana, and UnitedHealthcare (UHC) insurers were assessed. Humana implemented macular degeneration step therapy in 2019, setting bevacizumab as the plan-preferred drug, and aflibercept and ranibizumab as the plan-nonpreferred drugs. Aetna and UHC, which did not implement macular degeneration step therapy, served as the control group. Data analyses were performed from May 2024 to December 2024. Exposures: A macular degeneration drug administration subject to a step therapy policy. Main Outcome and Measures: A binary indicator of whether the drug administered was bevacizumab. Linear probability models and a difference-in-differences framework were used to quantify changes in prescribing patterns before and after the introduction of step therapy for MA insurers that did and did not implement step therapy. To empirically measure the impact of step therapy, the first administration of a treatment episode was assessed, followed by switching patterns. Results: A total of 18 331 MA beneficiaries, 21 683 treatment episodes, and 171 985 drug administrations were included across the control and treatment groups. The difference-in-differences regressions found a 7.8% (95% CI, 4.9%-10.7%; P < .001) greater probability of being prescribed bevacizumab for the first administration due to step therapy. The predicted probabilities of preferred-drug administration in the treatment group increased from 0.61 to 0.70 between the periods before and after step therapy implementation for the first administration. Step therapy was not significantly associated with an increased rate of medication switching (hazard ratio, 0.86; 95% CI, 0.71-1.06; P = .15). Conclusions and Relevance: The findings of this retrospective encounter-based analysis indicate that step therapy is associated with a greater probability of prescribing the plan-preferred drug for the first administration. The analysis failed to find a statistically significant greater rate of medication switching within a treatment episode. Step therapy changed macular degeneration prescribing patterns, but step therapy alone did not transition all administrations to the plan-preferred drug.

Comparison of One-Year Outcome of Intravitreal Aflibercept with or without Photodynamic Therapy for Polypoidal Choroidal Vasculopathy.

Background and Objectives: Our study compared the visual and anatomical outcomes of polypoidal choroidal vasculopathy (PCV) patients receiving intravitreal aflibercept (IVA) with or without photodynamic therapy (PDT) over 12 months. Materials and Methods: This retrospective study was performed for 60 eyes from 60 patients with treatment-naïve PCV. Thirty eyes were treated using IVA monotherapy (IVA group), and thirty eyes were treated using a combination of IVA with PDT (IVA/PDT group). The baseline characteristics, treatment outcomes, and retreatment rates were compared between the two groups over a one-year follow-up period. Results: The best-corrected visual acuity (BCVA) was found to have improved significantly in the IVA/PDT group at every 3-month visit. However, no significant BCVA improvement was observed in the IVA group. A significantly lower retreatment rate and higher dry macula rate were found in the IVA/PDT group than that in the IVA group. In the entire population of the study, a better baseline vision and younger age were associated with better final visual outcomes. Retreatment was associated with poor baseline BCVA and IVA monotherapy. Conclusions: The combination of IVA and PDT may offer superior visual improvement and a higher dry macula rate compared to IVA monotherapy in the treatment of PCV patients while requiring fewer retreatments over 12 months.

Aflibercept for central retinal vein occlusions: long-term outcomes of a 'Treat-and-Extend' regimen.

BACKGROUND/AIMS: This study reports on the long-term functional and anatomical outcomes of patients with central retinal vein occlusion (CRVO) treated under the Bern treat-and-extend (T&E) protocol. METHODS: Observational study. Treatment-naive patients with CRVO and consecutive macular oedema treated with aflibercept were included. The T&E protocol involved 2 monthly injections followed by an extension based on individual assessments. At each visit, best-corrected visual acuity (BCVA), optical coherence tomography imaging and a 2 mg aflibercept injection were administered. Changes in BCVA, proportion of patients gaining ≥15 letters, central subfield thickness (CST) and treatment intervals were analysed. RESULTS: Out of 173 patients, 64 had a follow-up of at least 2 years. BCVA improved from 46.7±25.3 at baseline to 78.3±0.5 at year 9. The proportion of patients with ≥15 letters gained was 56%, 53%, 56%, 62%, 52%, 52%, 43%, 50% and 33% at years 1-9, respectively. CST decreased significantly from 660±242 µm at baseline to 359±63 µm at year 9. Treatment intervals extended from 4 weeks initially to an average of 13.0±4.1 weeks by year 8. CONCLUSIONS: The T&E regimen for CRVO shows sustained visual improvements and reduced CST over time. Patients maintained stable visual gains for many years, demonstrating the effectiveness of this treatment approach. However, no control group was available to compare our T&E regimen with other strategies.

The effect of four loading intravitreal aflibercept injections on macular fluid in treatment-naïve neovascular age-related macular degeneration.

PURPOSE: To evaluate the effect of four versus three loading aflibercept injections on macular fluid resolution and visual acuity (VA) in exudative neovascular AMD (nAMD). METHODS: Multicentre, retrospective cohort study of treatment naïve nAMD eyes undergoing 3 versus 4 loading doses of aflibercept. Change in VA and fluid resolution on optical coherence tomography (OCT), were evaluated at 8 weeks post loading. The primary outcome was proportion of patients with no intraretinal (IRF) and/or subretinal (SRF) fluid at central 1 mm and whole macula at 8 weeks after loading. Data were summarised with mean ± SD for continuous variables, and n (%) for categorical variables. RESULTS: Data from 995 patients was analysed (355 patients - 4 loading doses and 640-3 loading doses). At 8 weeks post 4 loading doses proportion of eyes with neither IRF nor SRF, no IRF and no SRF were 62.8%, 88.7% and 79.2% at fovea versus 56.1%, 87.9% and 69.9% in the whole macula, respectively. Fluid resolution at both fovea and macula were significantly higher in eyes with 4 loading injections versus 3 (p = 0.0001). The mean VA change was +4.0 (±11.3) and +5.4(±13.3) letters for 3 and 4 loading doses groups (p = 0.09). CONCLUSION: Four loading dose injections of aflibercept results in higher proportion of eyes with total fluid resolution in the central subfield and total macular scan when compared to those receiving 3 loading dose injections at 8 weeks post loading phase. However, the better drying effect of 4th loading dose does not translate into better short-term VA outcomes.

Efficacy, durability, and safety of faricimab with extended dosing up to every 16 weeks in diabetic macular edema: 2-year results from the Japan subgroup of the phase 3 YOSEMITE trial.

PURPOSE: To evaluate the 2-year efficacy, durability, and safety of faricimab in patients with diabetic macular edema (DME) in the YOSEMITE Japan subgroup. STUDY DESIGN: YOSEMITE/RHINE (NCT03622580/NCT03622593) subgroup analysis: global, multicenter, randomized, double-masked, active-comparator-controlled, phase 3 faricimab trials. METHODS: Patients were randomized 1:1:1 to intravitreal faricimab 6.0 mg every 8 weeks (Q8W) and per treat-and-extend (T&E) dosing, or aflibercept 2.0 mg Q8W. Outcomes were assessed through year 2 for the YOSEMITE Japan subgroup (N = 60) and the pooled YOSEMITE/RHINE global cohort (N = 1891). RESULTS: In the YOSEMITE Japan subgroup, 21, 19, and 20 patients were randomized to faricimab Q8W, faricimab T&E, and aflibercept Q8W, respectively (632, 632, and 627 patients in the pooled YOSEMITE/RHINE cohort). Vision gains and anatomic improvements with faricimab at year 1 were maintained over 2 years and were generally consistent between groups. Mean best-corrected visual acuity changes from baseline at year 2 (weeks 92-100 average) for the YOSEMITE Japan subgroup were +12.5, +9.0, and +5.0 letters in the faricimab Q8W, faricimab T&E and aflibercept Q8W arms, respectively (+10.8, +10.4, and +10.3 letters in the pooled YOSEMITE/RHINE cohort). At week 96, 61.1% of the YOSEMITE Japan subgroup and 78.1% of the pooled YOSEMITE/RHINE cohort were on ≥ Q12W dosing. Faricimab was well-tolerated with a safety profile comparable with aflibercept. CONCLUSION: Faricimab up to Q16W offered durable vision gains and anatomic improvements up to 2 years in patients with DME in the YOSEMITE Japan subgroup. Outcomes were generally consistent with the pooled YOSEMITE/RHINE cohort.