Short-Term Comparison of Switching to Brolucizumab or Faricimab from Aflibercept in Neovascular AMD Patients.

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.

Association of Polyp Regression after Loading Phase with 12-Month Outcomes of Eyes with Polypoidal Choroidal Vasculopathy.

PURPOSE: 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.

Efficacy and safety of Brolucizumab for neovascular age-related macular degeneration: a systematic review and meta-analysis.

Background: To evaluate the efficacy and safety of Brolucizumab for neovascular age-related macular degeneration (n-AMD) through a systematic review and meta-analysis. Materials and Methods: Cochrane, PubMed, Embase, and Web of Science databases were comprehensively searched for relevant studies. Stata and RevMan5.4 were applied for meta-analysis and risk of bias assessment. Data on the best-corrected visual acuity (BCVA), central subfield thickness (CSFT), presence of intraretinal fluid (IRF) and/or subretinal fluid (SRF), participants with ≥1 serious adverse events, and participants with ≥1 adverse events were analyzed. Results: Six studies were finally included. Meta-analysis showed statistical differences in BCVA [SMD = -0.65, 95% CI [-0.17 to -0.23], P < 0.05], the presence of IRF and/or SRF [RR = 0.67, 95% CI [0.56-0.79], P < 0.05], and the safety of participants with ≥1 serious adverse events [RR = 0.57, 95% CI [0.39-0.84], P < 0.05] between the experimental group and the control group. However, no statistical differences were observed in CSFT [SMD = -1.16, 95% CI [-2.79 to 0.47], P > 0.05] or the safety of participants with ≥1 adverse events [RR = 1.07, 95% CI [0.97-1.17], P > 0.05]. Conclusions: Compared to other anti-VEGF drugs such as Aflibercept and Ranibizumab, intravitreal injection of 6 mg Brolucizumab is more effective and safer for n-AMD, especially in the presence of IRF and/or SRF, and for participants with ≥1 serious adverse events.

Safety and Effectiveness of Intravitreal Brolucizumab Injection in Combination With Sub-Tenon's Capsule Triamcinolone Acetonide Injection for Polypoidal Choroidal Vasculopathy During the Loading Phase.

BACKGROUND: This study evaluated the safety and effectiveness of combining intravitreal brolucizumab injection with sub-tenon's capsule triamcinolone acetonide injection (STTA) during the loading phase for polypoidal choroidal vasculopathy (PCV). METHODS: In this retrospective observational study, untreated patients with PCV receiving intravitreal brolucizumab injections with STTA during loading at Saitama Medical University Hospital's Eye Center from May 2021 to June 2022 were analyzed. Complete regression rates of polypoidal lesions were assessed using indocyanine green angiography 12 weeks post-treatment initiation. RESULTS: Nineteen patients (19 eyes) participated. Best-corrected visual acuity significantly improved at eight weeks compared to baseline. No significant intraocular pressure increases occurred throughout the loading phase, while central foveal and choroidal thickness significantly reduced at 4, 8, and 12 weeks. Subretinal fluid was present in all patients before treatment, rapidly resolving post-intravitreal brolucizumab injections and STTA, with residual rates of 36.8% (seven eyes) and 5.3% (one eye) at four and 12 weeks, respectively. Intraocular inflammation did not occur during the loading phase, and the complete regression rate of polypoidal lesions was 89.5% (17 eyes). CONCLUSIONS: Combining intravitreal brolucizumab injection with STTA during the loading phase may be one treatment option for PCV management.

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

PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Efficacy of Brolucizumab in Polyp Regression of Treatment-Naive Polypoidal Choroidal Vasculopathy and Its Effect on 1-Year Treatment Outcome.

PURPOSE: To evaluate the efficacy of intravitreal brolucizumab in polyp regression of treatment-naive polypoidal choroidal vasculopathy (PCV) patients and its effect on 1-year treatment outcome. METHODS: Medical records of 31 treatment-naive PCV patients, who received three monthly intravitreal brolucizumab injections followed by as-needed injections for at least a year, were retrospectively reviewed. Visual and anatomical outcomes were evaluated at 3, 6, and 12 months. Complete polyp regression rate and percentage change of vascular lesion and polyp area were evaluated after three monthly injections of brolucizumab. The effect of complete polyp regression and the impact of vascular lesion and polyp reduction rate on 1-year treatment outcome were also evaluated. RESULTS: In terms of visual outcome, best-corrected visual acuity significantly improved after 12-month follow-up (p < 0.001). In terms of anatomical outcome, central macular thickness (CMT) and central choroidal thickness significantly decreased after 12-month follow-up (p < 0.001). Complete polyp regression was observed in 23 patients (74.2%) after three monthly injections. Group with complete polyp regression had a higher rate of achieving dry macula at 3 months (p = 0.026) and fewer number of injections (p < 0.001) compared to the group without complete polyp regression. Higher polyp reduction rate was significantly associated with higher CMT change from baseline at 3 months (p = 0.048) while higher vascular lesion reduction rate was significantly associated with higher CMT change from baseline at 12 months (p = 0.031) and fewer number of injections (p = 0.012). CONCLUSIONS: Intravitreal brolucizumab injection effectively improved visual and anatomical outcomes and achieved significant polyp regression in treatment-naive PCV patients. Complete polyp regression and the reduction rate of vascular lesion size and polyp size after loading injection significantly influence the treatment outcome of PCV patients. However, careful monitoring and preoperative warning is warranted due to occurrence of brolucizumab-related IOI.

Exploring Current Molecular Targets in the Treatment of Neovascular Age-Related Macular Degeneration toward the Perspective of Long-Term Agents.

Long-lasting anti-vascular endothelial growth factor (anti-VEGF) agents have become an option to reduce treatment frequency, with ongoing research exploring optimal responses and safety profiles. This review delves into molecular targets, pharmacological aspects, and strategies for achieving effective and enduring disease control in neovascular age-related macular degeneration (AMD). The molecular pathways involved in macular neovascularization, including angiogenesis and arteriogenesis, are explored. VEGF, PlGF, Ang-1, and Ang-2 play crucial roles in regulating angiogenesis, influencing vessel growth, maturation, and stability. The complex interplay of these factors, along with growth factors like TGFß and bFGF, contributes to the pathogenesis of neovascular membranes. Current anti-VEGF therapies, including bevacizumab, ranibizumab, aflibercept, brolucizumab, and faricimab, are discussed with a focus on their pharmacokinetics and clinical applications. Strategies to achieve sustained disease control in AMD involve smaller molecules, increased drug dosages, and novel formulations. This narrative review provides a comprehensive overview of the molecular targets and pharmacological aspects of neovascular AMD treatment.

Evaluating photodynamic therapy versus brolucizumab as a second-line treatment for polypoidal choroidal vasculopathy.

BACKGROUND: To compare the one-year outcomes between intravitreal brolucizumab (IVBr) monotherapy and photodynamic therapy (PDT) as a second-line treatment in patients with polypoidal choroidal vasculopathy (PCV) who did not respond to first-line therapy. METHODS: This case-control study included eyes with PCV that do not respond to aflibercept or ranibizumab. The patients were retrospectively registered. We compared outcomes, including best-corrected visual acuity (BCVA), anatomical results, and the need for additional treatments, between IVBr and a combination therapy using PDT as second-line treatments for refractory PCV, after adjusting for potential confounders. We analyzed E-values to evaluate the robustness of the results against unmeasured confounders. RESULTS: Twenty-two eyes received IVBr, and twenty-four underwent PDT. No apparent differences were observed in BCVA and central macular thickness (CMT) changes from baseline between the groups (IVBr vs. PDT: BCVA, 0.01 ± 0.47 logMAR vs. 0.04 ± 0.18 logMAR, P-value = 0.756; CMT: - 36.3 ± 99.4 µm vs. - 114.7 ± 181.4 µm, P-value = 0.146). Only in the PDT group, five eyes (20.8%) did not require additional treatment after the second-line treatment, the adjusted odds ratio indicating no further treatment needed was 11.98 (95% confidence interval: 1.42-2070.07, P-value = 0.019). The E-value for the adjusted odds ratio was 23.44. CONCLUSIONS: Both second-line treatments for PCV exhibited similar visual and anatomical outcomes. Only in the PDT-treated eyes were there some patients who did not require further treatment after second-line therapy.

One-year visual and anatomical outcomes of intravitreal faricimab injection for neovascular age-related macular degeneration after prior brolucizumab treatment.

This single-center retrospective cohort study analyzed the 1-year real-world treatment outcomes of 63 consecutive eyes (of 60 patients) with neovascular age-related macular degeneration (nAMD) that were switched from intravitreal brolucizumab (IVBr) to intravitreal faricimab (IVF) and managed on a treat-and-extend regimen with discontinuation criteria. After the switch, patients opted to continue IVF, to switch back to IVBr, or receive photodynamic therapy (PDT). Thirty-eight patients continued IVF, 16 patients were switched back to IVBr, 2 patients received PDT, and 4 patients paused treatment. Best-corrected visual acuity (BCVA), central subfield thickness (CST), subfoveal choroidal thickness (sf-CT), and injection intervals were compared immediately before and 1 year after the initial IVF. Whereas there was no change in BCVA and CST; 0 [- 0.0969 to 0.125, P = 0.58], - 1.5 [- 27.8 to 13.5, P = 0.11] µm, respectively, sf-CT decreased significantly; - 19.5 [- 45.5 to 7.75, P = 0.015] µm. The patients switched back showed no significant change in sf-CT. The injection interval extended significantly in the IVF continuation and the switch-back group (2.0 and 3.0 weeks, respectively; [P = 0.0007 and 0.0078]) in eyes with a pre-switching interval of less than 12 weeks. Faricimab shows promise as a safe and effective alternative to brolucizumab for treating nAMD.

Central retinal artery occlusion after intravitreal brolucizumab injection for treatment-naïve neovascular age-related macular degeneration; a case report.

BACKGROUND: To report a case of central retinal artery occlusion (CRAO) after intravitreal injection of brolucizumab for a treatment-naïve neovascular age-related macular degeneration (nAMD) patient without comorbid cardiovascular disease history. CASE PRESENTATION: A 79-year-old Asian male without a cardiovascular disease history such as diabetes or hypertension underwent three times of monthly consecutive intravitreal brolucizumab injections for treatment of progressed nAMD in his left eye. Two days after the third injection, the patient presented with acute painless visual loss. Typical retinal whitening with a cherry red spot was observed on the fundus photograph, and retinal swelling with hyper-reflectivity was also identified on the optical coherence tomography (OCT) scan. On the fundus fluorescein angiography, arm-to-retina time and arteriovenous transit time were remarkedly delayed, but clinical findings suggesting an intraocular inflammation (IOI) were not observed. Therefore, CRAO was diagnosed, and anterior chamber paracentesis was administrated immediately. However, there had been no improvement in visual acuity during the follow-up period of three months, despite prolonged oral steroid and anti-platelet agent medication. CONCLUSIONS: In rare cases, patients without cardiovascular comorbidities can develop CRAO after intravitreal brolucizumab injection without gross evidence of IOI. Therefore, CRAO should always be in consideration and careful observation is required after intravitreal brolucizumab injection for nAMD patients with old age, even if the patient does not have any other cardiovascular disease history.

Choroidal Thickness and brolucizumab intravitreal injection: Cause or effect of intraocular inflammation?

PURPOSE: to analyze the structural changes of choroidal thickness in patients with brolucizumab-related exudative vitritis after intravitreal injection, using EDI-OCT. METHODS: One hundred eyes of one hundred patients, affected by exudative age related-macular degeneration treated with brolucizumab intravitreal injection between January 2022 and august 2023 at Eye clinic of University of Federico II Naples, were enrolled. All eyes underwent macular examination using Enhanced Deep Imaging-OCT (Spectralis, Heidelberg Engineering inc.) preoperatively and at each postoperative check (1, 3, 6, 12 months). Anterior segment evaluation at slit lamp before and after injection was performed. RESULTS: Of the 100 treated eyes, 4 showed inflammatory signs related to exudative vitreitis, with inflammation signs at slit lamp examination and confirmed by OCT and B scan ecography. EDI-OCT revealed, in all of these 4 patients, a significant increase of choroidal thickness compared to baseline. CONCLUSION: choroidal thickness could be correlated in the inflammatory response generated in patients undergoing treatment with brolucizumab.

Real-World Experience With Brolucizumab 6 mg for Diabetic Macular Edema.

Background This study aimed to assess functional and anatomical outcomes after one month of treatment with a single intravitreal injection (IVI) of brolucizumab in patients with diabetic macular edema (DME). Methodology A retrospective study was conducted on eyes with DME who received a single IVI of brolucizumab. The study was designed to assess visual function and optical coherence tomography (OCT) biomarkers at baseline and one month following a single brolucizumab IVI. A sub-analysis was conducted between the following two groups: group 1 - treatment with brolucizumab due to burden, needle phobia, or non-compliance (responders to standard anti-vascular endothelial growth factor (VEGF) or naïve); and group 2 - non-responsive to previous therapies (standard anti-VEGF ± corticosteroids). The main outcome measures included best-corrected visual acuity (BCVA; Early Treatment of Diabetic Retinopathy Study (ETDRS) letters), central foveal thickness, and OCT biomarkers such as the presence of subretinal fluid, the number of hyperreflective dots, the disorganization of retinal inner layers, the disruption of outer plexiform layer, external limiting membrane and ellipsoid zone, the presence of cysts in the nuclear layers (outer (ONL) and inner (INL)), and the number of cysts in ONL versus those in the INL. Safety outcomes were assessed. Results A total of 59 eyes from 42 patients were included, of which 47 eyes were in group 1 and 12 eyes were in group 2. At one month, patients had an improvement of two ETDRS letters on BCVA (p = 0.020), lower central foveal thickness (p < 0.001), fewer hyperreflective dots (p = 0.016), less outer plexiform layer disruption (p = 0.004), less inner and outer nuclear layer cysts (p < 0.001 and p = 0.001, respectively) and better relationship between ONL and INL cysts (p = 0.022). Results were significant in the subgroup of patients with previous responsive DME. No adverse events were reported. Conclusions This study demonstrates the effectiveness and safety after one injection of brolucizumab 6 mg in the management of DME, especially in previously responsive DME patients.

Scleritis following intravitreal brolucizumab injection: a case series.

BACKGROUND: This study reports the first cases of scleritis following intravitreal brolucizumab (IVBr) injection for nAMD, emphasizing the need to be aware of the possibility of scleritis following IVBr injections. CASE PRESENTATION: Case 1. A 74-year-old Japanese man with nAMD complained of conjunctivitis and decreased vision in the right eye 8 days after his eighth IVBr injection. Examination revealed scleritis without anterior inflammation. Topical 0.1% betamethasone and 0.3% gatifloxacin eye drops were started. The scleritis worsened in the following 2 weeks and became painful. He underwent sub-Tenon's capsule triamcinolone acetonide (STTA) injection. Two days later, he returned with a complaint of severe vision loss. Fundus examination revealed retinal artery occlusion, vasculitis, and vitreous opacity in the right eye. Vitreous surgery was performed. CASE 2: An 85-year-old Japanese woman with nAMD in the right eye complained of reddening of the eye 27 days after her fifth IVBr injection. Examination showed conjunctivitis and scleritis without anterior inflammation in the right eye. She was started on 0.1% fluorometholone and 0.5% levofloxacin hydrate eye drops. The scleritis worsened in the following 3 weeks. Her treatment was switched to 0.1% betamethasone eye drops. One month later, the scleritis had improved and a sixth IVBr injection was administered. There was no worsening of the scleritis at that time. However, 1 month after a seventh IVBr injection, she complained of severe hyperemia and decreased vision. Fundus examination revealed vitreous opacification. She underwent STTA, and the vitreous opacity improved in 24 days. Case 3. A 57-year-old Japanese man with nAMD complained of pain and decreased vision in the right eye 21 days after a fourth IVBr injection. Examination revealed scleritis with high intraocular pressure but no anterior chamber or fundus inflammation. STTA and topical eye drops were performed. One month later, scleritis improved but visual acuity didn't due to progression of nAMD. CONCLUSIONS: Intraocular inflammation following IVBr injection may progress to the posterior segment. Scleritis can occur after IVBr injection, and topical eye drops alone may not be sufficient for initial treatment. Clinicians should consider the possibility of scleritis in patients with worsening inflammation after IVBr injection.

Vitreous Opacity Following Intravitreal Brolucizumab Injection: A Case Series Review.

PURPOSE: To investigate cases of vitreous opacity (VO) similar to asteroid hyalosis (AH) after intravitreal brolucizumab injection. METHODS: A retrospective chart review was conducted to identify cases showing VO similar to AH among patients who received intravitreal brolucizumab injections at our retinal clinic from January 2022 to January 2023. RESULTS: A total of 220 brolucizumab injections were administered at our hospital. VO, showing yellow-white brilliant reflective particles, was found in six patients (2.7%). When VO occurred, all patients complained of floaters, although none of them complained of other symptoms including decreased visual acuity, pain, or conjunctival redness. The mean number of brolucizumab injections was 2.57 ± 2.38. No significant visual impairment was observed while VO was present. VO improved in all cases, and four cases improved without any treatment. The mean interval from onset to disappearance of VO was 8.0 ± 3.1 weeks. CONCLUSIONS: VO, similar to AH, can occur with a relatively high probability after intravitreal brolucizumab injections. Patients complained of severe floaters, but VO was not accompanied by other symptoms including vision impairment, injection, and pain. The VO disappeared after approximately 4 to 14 weeks. In case that other inflammatory findings are not severe, close follow-up without treatment may be sufficient. If a patient complains of floaters after an intravitreal brolucizumab injection, close fundus observation is necessary to evaluate the VO.

Cardiovascular Outcomes with Intravitreal Anti-Vascular Endothelial Growth Factor Therapy in Patients with Diabetes: A Real-World Data Analysis.

BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) therapy is commonly used intravitreally for diabetic proliferative retinopathy, but when used systemically for treating cancers, an excess of cardiovascular disease (CVD) events has been noted. The latter is of concern for people with diabetes, who are at higher risk of CVD. This study aims to explore the relationship between incident CVD and intravitreal anti-VEGF therapy in patients with diabetes, compared to other therapies, using a large real-world global federated dataset. METHODS: Data were analysed using TriNetX, a global electronic medical real-world ecosystem. The study included adults with diabetes and excluded those with a history of CVD prior to the time window of data extraction. Patients were categorised into two cohorts: anti-VEGF therapy or control cohort (laser or steroid therapies). The cohorts were 1:1 propensity score-matched for age, sex, ethnicity, body mass index, systolic blood pressure, HbA1c, and cardiovascular medications. Outcomes analysed at 1, 6 and 12 months were: (1) mortality; (2) acute myocardial infarction (MI); (3) cerebral infarction; and (4) heart failure. Relative risk analyses were performed using the built-in R statistical computing platform on TriNetX. RESULTS: In patients with diabetes (n = 2205; mean age 58.8 ± 15.8, Std diff 0.05; 56% male), anti-VEGF therapy was associated with a numerical but non-statistically significant increased CVD risk over 1, 6, and 12 months: Mortality over 1 month (RR 1; 95% CI 0.42, 2.40), 6 months (RR 1.46; 95% CI 0.72, 2.95) and 12 months (RR 1.41; 95% CI 0.88, 2.27). There was no excess of acute MI over 1 (RR n/a: not applicable; 0/0: 0 events in the anti-VEGF group/0 events in the control group), 6 and 12 months (RR n/a; 0/10 events); cerebral infarction over 1, 6 months (RR n/a; 0/0 events), and 12 months (RR n/a; 0/10); and heart failure over 1 month (RR n/a; 0/0 events), 6 months (RR 1; 95% CI 0.42, 2.40) and 12 months (RR 1; 95% CI 0.42, 2.34). CONCLUSIONS: There was no statistically significant risk of cardiovascular-related events in the short or medium term in patients with diabetes who received intravitreal anti-VEGF therapy, despite a small increase in the number of CVD events. Our study supports the real-world safety of intravitreal anti-VEGF therapy in patients with diabetes free of baseline CVD.

Flare levels after intravitreal injection of brolucizumab for diabetic macular edema.

PURPOSE: This study aimed to evaluate anterior flare intensity (AFI) after intravitreal injection of brolucizumab (IVBr) in patients with diabetic macular edema (DME), and to identify the factors associated with the change of AFI after IVBr. METHODS: This prospective multicenter study was conducted at five sites in Japan for patients with DME who underwent a single IVBr. AFI and central retinal thickness (CRT) were measured using a laser flare meter and spectral-domain optical coherence tomography, respectively, at weeks 0 and 6. RESULTS: Sixty-five patients (phakia, 37 eyes; pseudophakia, 28 eyes) were enrolled. Six weeks after IVBr, CRT and best-corrected visual acuity significantly improved (p < 0.0001). AFI (p = 0.0003) and age (p = 0.0054) were significantly higher in patients with pseudophakic eyes than those with phakic eyes. The AFI of the phakic eyes decreased after IVBr (p = 0.043). As the AFI before injection is higher (p = 0.0363) and the age is lower (p = 0.0016), the AFI decreases after IVBr. There was a significant positive correlation between the rates of change in CRT and AFI (p = 0.024). CONCLUSION: After IVBr, AFI decreases in phakic eyes but not in pseudophakic eyes. The age, AFI and CRT before injection and changes of CRT are involved in the change in AFI after IVBr.

Comparative efficacy of brolucizumab, half-dose photodynamic therapy, and aflibercept in managing chronic central serous chorioretinopathy.

PURPOSE: To compare the efficacy of brolucizumab, half-dose PDT, and aflibercept in treating chronic central serous chorioretinopathy (CSC). METHODS: A retrospective cohort study with chronic CSC patients who underwent intravitreal injection of one shot of brolucizumab or aflibercept in the first 3 months, followed by pro re nata regimens or a single session of half-dose PDT, was retrospectively reviewed. The primary outcome measure was the proportion of eyes that achieved complete absorption of retinal fluid without requiring any rescue treatment. Secondary outcomes included changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), and central choroidal thickness (CCT). RESULTS: A total of 54 consecutive patients were included in this study with 18 patients in each group. At months 1 and 2, the brolucizumab group exhibited the highest rate of complete retinal fluid resolution (61% and 77%), followed by the half-dose PDT group (56% and 72%), and lowest in the aflibercept group (28% and 33%), with statistically significant differences noted at month 2 (P = 0.012). The brolucizumab group also demonstrated the most significant reduction in CCT at months 1 and 2 among the three groups (P = 0.007 and 0.001). Recurrence of retinal fluid in the brolucizumab groups was predominantly observed at month 3. Conversely, the half-dose PDT group exhibited the most favorable anatomical results starting from month 3. Notably, mild vitritis was observed in one case from the brolucizumab group. CONCLUSIONS: Single injection of brolucizumab demonstrates trends of faster regression of persistent residual retinal fluid, greater CCT and CRT decline, and matched BCVA compared to half-dose PDT in the short term.

Changes in the uninjected contralateral eye after intravitreal brolucizumab for exudative age-related macular degeneration.

PURPOSE: Herein we describe the change in the amount of macular oedema in one eye after contralateral intravitreal brolucizumab injections in a patient with neovascular age-related macular degeneration (nAMD). CASE REPORT: A patient with bilateral nAMD underwent intravitreal bevacizumab injections in both eyes with little improvement in the best-corrected visual acuity (BCVA) and central macular exudation. The treatment was switched to aflibercept, but there was incomplete drying of the macula in both eyes. After uneventful cataract extraction, the central macular thickness (CMT) increased markedly in the operated left eye (LE), which was unresponsive to subtenon triamcinolone and further intravitreal aflibercept. Cataract surgery was also performed in the right eye (RE) combined with an intravitreal sustained-release dexamethasone implant. Nevertheless, the CMT increased. Intravitreal brolucizumab injections were performed in the RE with almost complete disappearance of the oedema in the treated eye. Concurrently, the contralateral uninjected eye showed a remarkable decrease in CMT. Five months after the first brolucizumab injection, the macular exudation increased again in both eyes. A second brolucizumab injection was performed in the RE only, and was followed by a prompt reduction in CMT in both the injected RE and uninjected LE. CONCLUSIONS: Although contralateral retinal changes have been described for many other vascular endothelial growth factor inhibitors, there is little evidence for brolucizumab. We describe a repeated dose- and time-related effect on the uninjected eye in a case of nAMD.

Brolucizumab for recalcitrant macular neovascularization in age-related macular degeneration with pigment epithelial detachment.

PURPOSE: To analyze anatomic and functional response to intravitreal brolucizumab in age-related macular degeneration recalcitrant to previous intravitreal anti-VEGF therapies. METHODS: In this monocentric, one arm, retrospective study, eyes affected by neovascular age-related macular degeneration (nAMD) resistant to other intravitreally injected anti-vascular endothelial growth factor inhibitors were switched to intravitreal brolucizumab. All patients underwent ophthalmological examinations at baseline and in regular follow-up intervals. Best registered visual acuity (BRVA), Goldmann tonometry, intraocular pressure (IOP), central retinal thickness (CRT) and pigment epithelial detachment (PED) characteristics were analyzed at initiation of anti-VEGF treatment, at treatment switch, and at the end of brolucizumab loading phase. RESULTS: The study included 20 eyes of 18 consecutively treated patients (age: 77 ± 6 years). All eyes had macular neovascularization with PED. Previous treatments included intravitreal aflibercept, bevacizumab, and ranibizumab and had not resulted in a significant improvement in BRVA (0.5 ± 0.5 logMAR vs 0.5 ± 0.6 logMAR) or mean CRT (320 ± 60 µm vs 313 ± 83 µm) up to treatment switch to brolucizumab. At the end of the brolucizumab loading phase, there was significant improvement for both BRVA (0.3 ± 0.2 logMAR, P < 0.05) and CRT (264 ± 55 µm, P < 0.05). Under previous anti-VEGF therapy, there was a significant increase/deterioration in both PED area (2.68 mm2 to 5.18 mm2, P < 0.05) and PED volume (0.39 mm3 to 1.07 mm3, P < 0.05); however, both parameters improved after switching to brolucizumab (3.81 mm2 and 0.37 mm3, P < 0.05). CONCLUSION: Our results suggest a favourable anatomical and visual response after treatment switch to brolucizumab in patients with nAMD refractory to previous anti-VEGF agents.

Comparison of functional and morphologic changes between brolucizumab and faricimab in neovascular age-related macular degeneration.

PURPOSE: This study aimed to compare functional and morphologic changes in the loading phase between patients with treatment-naïve macular neovascularization (MNV) due to neovascular age-related macular degeneration (nAMD) treated with either intravitreal brolucizumab (IVBr) or intravitreal faricimab (IVF) injections in a clinical setting. METHODS: We retrospectively studied 92 consecutive eyes of 90 patients with neovascular nAMD who were scheduled to receive IVBr (42 eyes of 41 patients) or IVF (50 eyes of 49 patients) injections between October 2021 and December 2022. All patients received three consecutive monthly injections of 6.0 mg/0.05 mL brolucizumab or 6.0 mg/0.05 mL faricimab. The best-corrected visual acuity (BCVA), central foveal thickness (CFT), and central choroidal thickness (CCT) at baseline and 1, 2, and 4 months after the initial treatment were measured and compared between the groups. RESULTS: Thirty-seven eyes in IVBr group and forty-seven eyes in IVF group who finished treatments in the loading phase were assessed at the follow-up examination. The BCVA, CFT, and CCT changed significantly after loading phase in both groups (P < 0.05 for both comparisons). The IVBr group had more rapid improvement of the BCVA (P = 0.037) at 1 month than the IVF group, but there was no difference at 4 months (P = 0.367). The CFT and CCT decreases tended to be greater in the IVBr group than in the IVF group throughout the follow-up period. Of the five eyes excluded from the IVBr group, one eye (2.4%) each had intraocular inflammation (IOI) and was a non-responder, and two eyes (4.8%) had retinal pigment epithelial tears after treatment. Of the three eyes excluded from the IVF group, two eyes (4.0%) did not respond to the treatment. CONCLUSIONS: Both IVBr and IVF injections were well-tolerated and improved the VA in treatment-naïve patients with MNV due to nAMD after a loading phase, although IVBr caused a trend toward faster visual improvements in the BCVA. The IVBr group also had greater reductions of the CFT and CCT than the IVF group. However, the potential for adverse events and no response to treatment with each drug are considerations.