Two-year outcomes of intravitreal brolucizumab for neovascular age-related macular degeneration: treat, extend, and stop-protocol.

To investigate the real-world 2-year treatment outcomes of intravitreal brolucizumab (IVBr) for neovascular age-related macular degeneration (nAMD). 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. 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. 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. UMIN Clinical Trials Registry ( http://www.umin.ac.jp/ ; R000050688 UMIN 000044374).

Yoshida H ，Inoda S ，Takahashi H ，Takahashi R ，Hashimoto Y ，Takahashi H ，Kawashima H ，Yanagi Y ... -  《-》

Long-term efficacy and safety of brolucizumab in neovascular age-related macular degeneration: A multicentre retrospective real-world study.

To investigate the long-term efficacy and safety of intravitreal brolucizumab (BRZ) injections in patients with typical neovascular age-related macular degeneration (typical nAMD) and polypoidal choroidal vasculopathy (PCV). This multicentre retrospective study included 401 eyes of 398 patients with nAMD who received BRZ injection(s), with a follow-up duration of ≥12 months. Changes in best-corrected visual acuity (BCVA), retinal fluid evaluation and central subfield thickness (CST) on optical coherence tomography were assessed. The efficacy of BRZ was compared between typical nAMD and PCV groups. Analyses were conducted with 280 eyes of 278 patients with typical nAMD and 121 eyes of 120 patients with PCV (mean age, 71.1 ± 8.6 years). 29 eyes (7.2%) were treatment naïve. The mean follow-up period was 15.3 ± 2.8 months; the mean number of BRZ injections within 1 year was 4.5 ± 1.7. BCVA was maintained during the follow-up period, and CST significantly improved from the first injection month and was maintained for 12 months in both the typical nAMD and PCV groups. The dry macula proportion increased from 2.7% at baseline to 56.1% at 1 month and 42.9% at 12 months. Among the 18 eyes that underwent indocyanine green angiography both before and after treatment, 10 (55.6%) showed polyp regression. Overall, the incidence of intraocular inflammation (IOI), retinal vasculitis and occlusive retinal vasculitis was 9.4% (38 eyes), 1.2% (5 eyes) and 0.5% (2 eyes), respectively. IOI occurred from the first to the sixth injections, with an average IOI onset of 28.5 ± 1.4 days. All eyes achieved IOI resolution, although the two eyes with occlusive retinal vasculitis showed a severe visual decline after IOI resolution. Brolucizumab was effective in maintaining BCVA and managing fluid in eyes with nAMD for up to 1 year, exhibiting a high polyp regression rate. However, the not uncommon incidence of IOI and the severe visual decline caused by the rare occlusive retinal vasculitis following BRZ treatment underscore the importance of careful monitoring and timely management.

Kim DJ ，Kim DG ，Kwak HD ，Jang JY ，Ji YS ，Lee SH ，Lee EK ，Park KH ，Kim JH ，Lee JS ，Song Y ，Kim ST ，Shin MH ，Kim M ，Park SJ ，Joo K ，Sagong M ，Lee CS ，Woo SJ ... -  《-》

Initial experience with brolucizumab for neovascular age-related macular degeneration (nAMD) in India - Multicentric, real-world study.

To evaluate the anatomic and visual outcomes and safety profile of initial Indian eyes with neovascular age-related macular degeneration (nAMD) treated with intravitreal injection (IVI) of brolucizumab. This retrospective multicentric, real-world study enrolled consecutive eyes with nAMD that were treated with IVI brolucizumab after it was launched in India in October 2020. Data collected for each eye included best-corrected visual acuity (BCVA), central subfield thickness (CSFT), subretinal fluid (SRF), and intraretinal fluid (IRF) status at 6, 12, and 24 months follow-up. Also recorded were the lens status, treatment protocol, number of injections received before enrollment (in switch-over cases), total number of injections, and adverse effects noticed during the study period. Primary outcomes were change in BCVA, CSFT at follow-up visits, and incidence of intraocular inflammation (IOI). Secondary outcomes were profile of macular neovascularization, treatment protocols, mean number of injections, and maximum injection-free interval observed in eyes treated by pro-re-nata (PRN) protocol. In total, 331 eyes received a mean of 3.55 ± 1.83 injections. Most frequent treatment protocol was PRN (53%). BCVA data was available for 100%, 96%, and 74% eyes at 6, 12, and 24 months follow-up. BCVA and CSFT improved significantly (P < 0.001) at all follow-ups. Two hundred and seventy-six (83.38%) out of 331 eyes received more than one injection; out of these, 241 (87.3%) eyes that were treated by PRN protocol could achieve mean "maximum injection-free interval" of 19.43 ± 8.82 weeks. IOI and retinal vasculitis were reported in 2.11% (7/331) and 0.60% (2/331) eyes, respectively. None of the eyes with IOI or vasculitis lost any vision at the final follow-up. This study demonstrated favorable visual and anatomic outcomes and safety profile for eyes with nAMD treated by IVI brolucizumab. Mean maximum injection-free interval in eyes treated with PRN was 19 weeks.

Singh DV ，Agarwal A ，Goyal A ，Shroff D ，Singh J ，Kumar P ，Reddy RR ，Venkatesh R ，Narnaware S ，Joshi S ，Singh DV ，Narula R ，Joshi A ，Agarwal A ，Goyal A ，Gupta C ，Shroff D ，Anantharaman G ，Singh J ，Kumar P ，Bawankule P ，Reddy RR ，Jain R ，Venkatesh R ，Tiwari R ，Sugumar S ，Gupta SR ，Narnaware S ，Joshi S ，Choudhary SP ，Delhi Retina Forum Study Group ... -  《-》

First-year real-world experience of intravitreal brolucizumab injection for refractory neovascular age-related macular degeneration.

To investigate the first-year real-world anatomical and functional outcomes of intravitreal brolucizumab injection in eyes with refractory neovascular age-related macular degeneration (nAMD). Retrospective observational study. nAMD patients who showed poor response to previous anti-vascular endothelial growth factor (VEGF) agents were switched to brolucizumab. Functional and anatomical outcomes were evaluated at initial treatment of nAMD, after treatment with other anti-VEGF agents and after switching and treating with brolucizumab for 1 year. Safety profile was also evaluated after brolucizumab injection. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), subfoveal choroidal thickness (SFCT), and the presence of fluid in different compartments (intraretinal fluid [IRF], subretinal fluid [SRF], pigment epithelial detachment [PED]) were assessed at each time point. A total of 40 eyes of 40 patients were included in the study. BCVA remained unchanged throughout treatment (p > 0.05). CFT did not change after treatment with other anti-VEGF agents (p = 0.588) but decreased after switching to brolucizumab (p < 0.001). SFCT decreased after treatment with other anti-VEGF agents (p = 0.025) but not after switching to brolucizumab (p = 0.236). Presence of SRF (p = 0.001) and PED (p = 0.001) decreased significantly after switching to brolucizumab, despite their persistence with prior treatments using other anti-VEGF agents. However, IRF persisted even after switching to brolucizumab (p = 0.745). Intraocular inflammation (IOI)-related adverse events were reported in 3 eyes (7.14%). Analysis of first-year real-world outcomes after switching to brolucizumab in nAMD patients refractory to other anti-VEGF agents showed improved anatomic outcomes, limited functional improvement and low incidence of IOI-related adverse events.

Lee JH ，Shin JY ，Ahn J 《-》

Efficacy of switching to brolucizumab for neovascular age-related macular degeneration refractory to faricimab.

To evaluate the treatment outcomes of switching to intravitreal brolucizumab (IVBr) for neovascular age-related macular degeneration (nAMD) which did not achieve a dry macula even with 4- or 8-week intervals of intravitreal faricimab (IVF). Retrospective, interventional case series. We retrospectively studied 33 eyes of 33 consecutive patients with nAMD who switched to IVBr from IVF, assessing best corrected visual acuity (BCVA), foveal thickness (FT), central choroidal thickness (CCT), and exudative status at baseline and after the switch. For patients that switched 4 weeks after the last IVF (4-week interval group), treatment outcomes were evaluated 4 weeks after the switch. For patients that switched 8 weeks after the last IVF (8-week interval group), treatment outcomes were evaluated after the first 8-week interval following the switch. Thirty-one eyes had completed IVBr treatment up to the evaluation point after the switch. There were no significant changes in BCVA at baseline and after the switch in either group. FT and CCT significantly decreased after the switch compared with baseline in both groups. Moreover, in both groups, exudative changes disappeared or decreased in most cases after the switch. The dry macula rate after the switch was 37.5% and 34.8% in the 4-week and 8-week interval group, respectively. Although brolucizumab-related intraocular inflammation was observed in 3 eyes (9.1%) after the switch, it was ameliorated in response to steroid therapy. Switching to IVBr for nAMD refractory to IVF was generally effective in improving exudative changes in the short term.

Hoshino J ，Matsumoto H ，Nakamura K ，Akiyama H ... -  《-》