OBJECTIVE: This study analyzes the effectiveness and safety of brolucizumab in the treatment of neovascular age-related macular degeneration (nAMD) in real clinical practice.
METHODS: The study included patients with nAMD who received brolucizumab treatment and evaluated the changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), macular volume, as well as the number of injections and adverse events.
RESULTS: The group of previously treated patients included 28 subjects (28 eyes) that were switched to brolucizumab with a loading phase. By 12 months, BCVA changed from 0.43±0.29 to 0.33±0.27 LogMAR (p=0.11), CRT decreased from 281.5±58.2 to 239.9±45.6 µm (p=0.02). The group of previously untreated patients included 29 subjects (29 eyes). By 12 months, BCVA changed from 0.47±0.32 to 0.40±0.30 LogMAR (p=0.09), CRT decreased from 333.2±77.3 to 226.2±49.6 µm (p<0.001). Patients received 6.3±0.7 injections. In this group, baseline choroidal thickness showed a statistically significant correlation with final visual acuity (r=0.54; p<0.05) and CRT (r= -0.5; p<0.05). The group of previously treated patients switched without a loading phase included 18 patients (18 eyes). By 6 months, BCVA changed from 0.42±0.2 to 0.37±0.26 LogMAR (p=0.42). CRT remained stable at 285.6±56.9 µm (p=0.97). No adverse events related to intraocular inflammation were reported during the course of 385 injections.
CONCLUSIONS: Brolucizumab therapy helps achieve significant anatomical and functional improvements in real clinical practice both in patients switched from previous treatments and in treatment-naïve patients. Greater baseline choroidal thickness may be associated with better anatomical and functional outcomes with brolucizumab treatment.
UNASSIGNED: Проанализировать эффективность и безопасность применения бролуцизумаба в лечении неоваскулярной возрастной макулярной дегенерации (нВМД) в условиях реальной клинической практики.
UNASSIGNED: В исследование были включены пациенты с нВМД, получавшие лечение бролуцизумабом. Оценивали динамику максимальной корригированной остроты зрения (МКОЗ), центральной толщины сетчатки (ЦТС), макулярного объема, число инъекций и нежелательные явления.
UNASSIGNED: В группу пациентов, ранее получавших лечение и переведенных на бролуцизумаб с фазой загрузки, было включено 28 человек (28 глаз). К 12 мес наблюдения МКОЗ изменилась с 0,43±0,29 до 0,33±0,27 LogMAR (p=0,11), ЦТС уменьшилась с 281,5±58,2 до 239,9±45,6 мкм (p=0,02). В группу пациентов, ранее не получавших лечение, было включено 29 человек (29 глаз). К 12 мес МКОЗ изменилась с 0,47±0,32 до 0,40±0,30 LogMAR (p=0,09), ЦТС уменьшилась с 333,2±77,3 до 226,2±49,6 мкм (p<0,001). Пациенты получили 6,3±0,7 инъекции. В этой группе исходная толщина сосудистой оболочки показала статистически значимую связь с окончательной остротой зрения (r=0,54; p<0,05) и ЦТС (r= –0,5; p<0,05). В группу пациентов, ранее получавших лечение и переключенных без фазы загрузки, было включено 18 человек (18 глаз). К 6 мес МКОЗ изменилась с 0,42±0,2 до 0,37±0,26 LogMAR (p=0,42). ЦТС к 6 мес осталась стабильной — 285,6±56,9 мкм (p=0,97). При проведении 385 инъекций не было зарегистрировано нежелательных явлений, связанных с внутриглазным воспалением.
UNASSIGNED: Терапия бролуцизумабом в реальной клинической практике позволяет добиться существенного анатомического и функционального улучшения как при переключении с проводимого лечения, так и у ранее не леченных пациентов. Большая исходная толщина сосудистой оболочки может быть связана с лучшими анатомо-функциональными исходами при лечении бролуцизумабом.

OBJECTIVE: To report the safety and efficacy of brolucizumab (Beovu®) 6 mg vs. aflibercept (Eylea®) 2 mg administered every 4 weeks in participants with neovascular age-related macular degeneration (nAMD) and persistent retinal fluid after the Week 52 primary endpoint analysis (from Week 52 up to Week 104, post-study termination).
METHODS: Multicenter, randomized, double-masked Phase 3a study.
METHODS: Participants with recalcitrant nAMD (persistent residual retinal fluid despite previous frequent anti-vascular endothelial growth factor treatment).
METHODS: Study eyes were randomized 2:1 to intravitreal brolucizumab 6 mg or aflibercept 2 mg every 4 weeks for 100 weeks, or until study termination.
METHODS: All available efficacy (analysis of noninferiority in mean best-corrected visual acuity [BCVA], central subfield thickness [CST], fluid-free status [no intraretinal fluid and no subretinal fluid]), and safety data up to study termination, including data up to Week 104 for those participants who completed the study prior to its termination. All P values after Week 52 were nominal and reflect observed data for the efficacy analyses.
RESULTS: Brolucizumab 6 mg every 4 weeks was noninferior to aflibercept 2 mg in mean BCVA change from baseline to Week 104 (least squares mean difference, -0.4 Early Treatment Diabetic Retinopathy Study letters; 95% confidence interval [CI], -3.7 to 3.0; P = 0.0169). The proportion of eyes with ≥15-letter loss was 6.2% for brolucizumab and 4.7% for aflibercept. (P = 0.0014), and a greater proportion of eyes were fluid free at Week 104 (52.5% brolucizumab vs. 28.2% aflibercept; 95% CI, 11.9-37.3; P < 0.001) in eyes treated with brolucizumab vs. aflibercept. Incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, was 11.5% (0.8% and 2.2%) for brolucizumab vs 6.1% (0% and 0.6%) for aflibercept, respectively.
CONCLUSIONS: Consistent with 52-week results, brolucizumab 6 mg every 4 weeks was noninferior in mean BCVA change with anatomic outcomes superior to aflibercept 2 mg every 4 weeks from baseline to Week 104 or study termination. The incidence of IOI, including retinal vasculitis and retinal vascular occlusion, was higher with brolucizumab vs. aflibercept; therefore, brolucizumab should not be used more frequently than every 8 weeks following the loading regimen.

OBJECTIVE: To determine the efficacy and safety of brolucizumab therapy administered on a pro re nata (PRN) basis without loading dose in treatment naïve patients with diabetic macular edema (DME) for 1 year follow-up.
METHODS: Patients with recent DME (<6 months) received a mandatory brolucizumab injection at inclusion and other injections could be given on a PRN basis with an 8-week interval (between injections) at minimum. Rescue therapy with other anti-VEGF was possible in case of incomplete DME resolution after the second brolucizumab with a minimum of 1-month treatment free interval between 2 injections. The primary outcome measure was the change in (BCVA) at 12 months. Secondary outcome measures included the change in central subfield thickness (CST), the change in hard exudate surface area and microaneurysms at 1 year.
RESULTS: A total of 53 patients were included. At 12 months, the mean (SD) number of injections was 2.6 (0.8) in addition to the first mandatory injection. The mean (SD) interval between 2 consecutive injections was 3.2 (1.4) months. The mean (SD) BCVA improved from 0.62 (0.1) logMAR to 0.40 (0.16) logMAR (p = 0.012). The mean CST reduced from 397.0 (47.2) µm to 224.5 (28.1) µm (p = 0.013). The hard exudate surface area decreased significantly (p = 0.012) as did microaneurysms (p = 0.02). Seven patients required at least 1 rescue therapy. No patients experienced intra-ocular inflammatory adverse events.
CONCLUSIONS: Brolucizumab therapy for DME is a safe and effective modality for the treatment of recent DME and has the potential to reduce the number of injections.

BACKGROUND: The purpose of this study is to identify the factors affecting neovascular age-related macular degeneration (nAMD) disease stability after brolucizumab treatment.
METHODS: We retrospectively analyzed the medical records of 31 patients (31 eyes) with recalcitrant nAMD who were switched to brolucizumab after conventional anti-vascular endothelial growth factor (VEGF) treatment. We divided patients into two groups by treatment extension (TE) period: group 1 with TE < 12 weeks (N = 16) and group 2 with TE ≥ 12 weeks (N = 15). We compared outcomes between the groups at 2, 4, 8, and 12 weeks, including morphological characteristics of choroidal neovascularization (CNV). Logistic regression analysis identified factors associated with TE ≥ 12 weeks.
RESULTS: Group 2 had a significantly greater proportion of patients with dry macula (subretinal and intraretinal fluids absent) than group 1 (60 vs. 12.5%) at 2 weeks (P < 0.05). Best-corrected visual acuity (BCVA) and subfoveal choroidal thickness (SFCT) did not differ significantly between groups at all timepoints. Central subfield retinal thickness (CST) was significantly lower in group 2 at 2 (237.1 vs. 280.8 μm; P < 0.05), 4 (224.0 vs. 262.9 μm; P < 0.05), and 8 weeks (216.8 vs. 331.1 μm; P < 0.05). Group 2 had less vessel area (0.63 vs. 1.27 mm2; P < 0.05) and total vessel length (0.22 vs. 0.42 mm; P < 0.05). Choriocapillaris flow deficit (CCFd) was significantly lower in group 2 (42.7 vs. 48.2%; P < 0.05). Dry macula at 2 weeks (odds ratio [OR] = 8.3; P < 0.05) and a lower CCFd (OR = 0.73; P < 0.05) were associated with TE ≥ 12 weeks.
CONCLUSIONS: Early fluid-free status after switching to brolucizumab and choriocapillary function around CNV were prognostic factors for disease stability in nAMD refractory to anti-VEGF treatment.

Objective: To purpose of this study was to retrospectively evaluate the 1-year outcomes and factors associated with the treatment responsiveness of switching to intravitreal brolucizumab (IVBR) for neovascular age-related macular degeneration (nAMD) in Japanese patients refractory to ranibizumab or aflibercept using a treat and extend (TAE) regimen. Methods: A total of 48 eyes of 47 nAMD patients were switched to IVBR, and 36 eyes of 35 patients (27 males and 8 females) underwent 1-year treatment after the switch. Results: The rate of dry macula was significantly higher 12 months after the switch to IVBR (p < 0.001), with a significant decrease in the mean central macular thickness (CMT) and the mean central choroidal thickness (CCT) (p < 0.01 and p < 0.01, respectively). The injection interval was significantly extended from 7.0 ± 1.7 weeks to 10.3 ± 2.5 weeks 12 months after the switch (p < 0.001). In the multivariate analysis, a smaller number of prior anti-VEGF injections (p = 0.025; odds ratio: 0.947; 95% confidence interval: 0.903-0.994) and a pre-switching CCT of less than 250 µm (p = 0.023; odds ratio: 0.099; 95% confidence interval: 0.013-0.731) were associated with the good response group. Conclusions: These results suggest that IVBR may suppress disease activity and prolong the injection interval by switching for AMD patients with an insufficient response to treatment with ranibizumab and aflibercept.

Background and Objectives: In this study, our objective was to assess and compare the changes in visual and structural outcomes among patients with neovascular age-related macular degeneration (nAMD) who were switched from intravitreal aflibercept (IVA) to either intravitreal brolucizumab (IVBr) or intravitreal faricimab (IVF) injections in a clinical setting. Materials and Methods: This observational clinical study included 20 eyes of 20 patients switched to brolucizumab and 15 eyes of 14 patients switched to faricimab from aflibercept in eyes with nAMD. We measured the structural outcome (central macular thickness (CMT)) and the visual outcome (best-corrected visual acuity (BCVA); logMAR) as follows: just before the most recent IVA injection (B0), one month after the most recent IVA injection (B1), just before the first IVBr or IVF injection (A0), one month after (A1) and three months after (A3) the first IVBr or IVF injection. Results: BCVA showed significant improvement at A1 (0.25 ± 0.34) and at A3 (0.19 ± 0.24) compared to A0 (0.38 ± 0.35) in the IVBr group (p = 0.0156, p = 0.0166, respectively). CMT (μm) was significantly thinner at A1 (IVBr: 240.55 ± 51.82, IVF: 234.91 ± 47.29) and at A3 (IVBr: 243.21 ± 76.15, IVF: 250.50 ± 72.61) compared to at A0 (IVBr: 303.55 ± 79.18, IVF: 270.33 ± 77.62) in the IVBr group (A1: p = 0.0093, A3: p = 0.0026) and in the IVF group (A1: p = 0.0161, A3: p = 0.0093). There was no significant difference in BCVA and CMT improvement observed between two groups at any time point (p > 0.05 for all). Conclusions: Switching from aflibercept to either brolucizumab or faricimab has a significant anatomical effect in eyes with nAMD and both treatments appear to be effective short-term treatment options. There is a trend towards greater visual improvements and reductions in CMT with brolucizumab.

OBJECTIVE: To compare the efficacy of brolucizumab and aflibercept treatment in reducing the maximum thickness of pigment epithelial detachments (PEDs) and sub-retinal pigment epithelium (sub-RPE) fluid in patients with neovascular age-related macular degeneration in the HAWK and HARRIER studies.
METHODS: HAWK and HARRIER were 96-week, prospective, randomized, double-masked, controlled, multicenter studies.
METHODS: A total of 1775 patients across 11 countries were included in the HAWK study, and 1048 patients across 29 countries were included in the HARRIER study.
METHODS: After 3 monthly loading doses, brolucizumab-treated eyes received injections every 12 weeks or every 8 weeks if disease activity (DA) was detected. Aflibercept-treated eyes received fixed 8-week dosing.
METHODS: Maximum thickness of PEDs and sub-RPE fluid across the macula were assessed at baseline through week 96 in the brolucizumab- and aflibercept-treated patients and in the patient subgroups with DA at week 16 (matched in terms of injection number and treatment interval).
RESULTS: At week 96, there were greater mean percentage reductions from baseline in maximum thickness of both PEDs and sub-RPE fluid in brolucizumab-treated patients vs. aflibercept-treated patients (PED: 19.7% [n = 336] vs. 11.9% [n = 335] in HAWK; 29.5% [n = 364] vs. 18.3% [n = 361] in HARRIER. Sub-RPE fluid: 75.4% vs. 57.3% in HAWK; 86.0% vs. 76.3% in HARRIER). A similar trend in mean percentage reductions was observed in patients with DA at week 16.
CONCLUSIONS: This analysis shows that brolucizumab achieved greater reductions in PEDs and sub-RPE fluid thickness than aflibercept in HAWK and HARRIER.
BACKGROUND: ClinicalTrials.gov Identifiers: NCT02307682 (HAWK) and NCT02434328 (HARRIER).
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

OBJECTIVE: To investigate the real-world 2-year treatment outcomes of intravitreal brolucizumab (IVBr) for neovascular age-related macular degeneration (nAMD).
METHODS: This multicenter, prospective, and interventional study included 53 eyes treated with brolucizumab from October 2020 to August 2021 at 3 institutions. A modified treat-and-extend (TAE) regimen with predefined discontinuation criteria was used. The mTAE regimen was discontinued if patients responded positively and achieved a treatment interval of 16 weeks twice with no sign of recurrence. The number of patients discontinuing TAE and the visual and anatomic changes at 1 and 2 years after the first IVBr were evaluated.
RESULTS: Thirty-eight eyes from 38 patients (71%) completed the 2-year observation period and 7 eyes from 7 patients experienced intraocular inflammation (IOI). Of these 38 patients, 18 (47%) could discontinue the TAE at a median [interquartile range] of 13.1 [12.9-16.8] months after the first IVBr. Best-corrected visual acuity, central subfield retinal thickness, and central choroidal thickness were significantly improved compared with baseline at both 1 and 2 years after the first IVBr (all P < 0.001). An extension study revealed a 1-year recurrence rate of 5.6% (standard deviation, 5.4%) after TAE discontinuation.
CONCLUSIONS: While IOI is a concern with brolucizumab, careful observation allows discontinuing the TAE regimen in patients treated with IVBr. Moreover, brolucizumab may reduce the risk of recurrence after treatment interruption.
BACKGROUND: UMIN Clinical Trials Registry ( http://www.umin.ac.jp/ ; R000050688 UMIN 000044374).

OBJECTIVE: We compared 12-month outcomes of eyes with polypoidal choroidal vasculopathy (PCV) with or without complete regression of polyps observed one month after three monthly intravitreal administrations (loading phase) of aflibercept (2.0 mg/0.05 mL) or brolucizumab (6.0 mg/0.05 mL).
METHODS: All patients underwent indocyanine green angiography at both baseline and 3 months after initial injection and were followed up monthly with an as-needed regimen for up to 12 months. A total of 62 patients with PCV were included: 30 eyes were treated with brolucizumab, and 32 were treated with aflibercept. Eyes with complete regression of polyps (regression group) had significantly smaller maximum polyp diameter and were more frequently treated with brolucizumab than those without complete regression (non-regression) group.
RESULTS: Best corrected visual acuity was comparable between the two groups at 12 months. Although the 12-month retreatment-free proportion was comparable between the two groups (33.0% versus 27.0%, p = 0.59), a retreatment-free period was significantly longer in the regression group than in the non-regression group (8.3 ± 3.3 versus 6.5 ± 3.6 months, p = 0.022), and the number of additional injections was significantly fewer in the regression group than in the non-regression group (1.2 ± 1.2 versus 3.0 ± 2.6, p = 0.007).
CONCLUSIONS: Complete regression of polyps observed after the initial phase possibly prolongs the retreatment-free period and reduces the number of additional injections irrespective of aflibercept or brolucizumab.

Background/Objectives: This study aimed to assess the effectiveness of bi-monthly brolucimumab treatment in patients with neovascular age-related macular degeneration (nAMD) refractory to monthly aflibercept treatment. Methods: A retrospective chart review included 32 eyes of patients with refractory nAMD who switched from monthly intravitreal aflibercept treatment to bi-monthly intravitreal brolucizumab treatment. This study evaluated changes in visual acuity (VA), intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), and central macular thickness (CMT), at specific times as follows: baseline before switching (T0), 2 months after switching (T1), 4 months after switching (T2), and 6 months after switching (T3). Results: The mean best-corrected visual acuity (BCVA) did not significantly change across all time points (0.52 ± 0.12, 0.48 ± 0.27, 0.48 ± 0.28, and 0.50 ± 0.27 logarithms of the minimum angle of resolution in T0, T1, T2, and T3, respectively). CMT significantly decreased after additional brolucizumab injections compared to the baseline (218.2 ± 48.6 and 207.9 ± 49.8 μm, respectively; p = 0.001). The PED height also significantly decreased from 251.0 ± 165.4 to 154.4 ± 115.65 μm (p < 0.001), with complete resolution in nine patients (28%). The mean subfoveal choroidal thickness (SFCT) before brolucizumab treatment was 262.8 ± 79.7 μm, which decreased to 233.0 ± 71.2 μm (p = 0.001) after the first injection. The final SFCT also significantly decreased after additional brolucizumab injections compared to the baseline SFCT (p = 0.012). Conclusions: Bi-monthly brolucizumab treatment proves effective for patients refractory to monthly fixed aflibercept, resulting in positive anatomical changes without significant deterioration in visual acuity. This approach provides a promising prognosis while reducing the treatment burden on refractory patients.