Long acting delivery and therapies for neovascular age-related macular degeneration.

INTRODUCTION: Neovascular age-related macular degeneration (nAMD) represents a leading cause of severe visual impairment in individuals over 50 years of age in developed nations. Intravitreal anti-vascular endothelial growth factor (VEGF) injections have become the standard of care for treating nAMD; however, monthly or bimonthly dosing represents significant time and cost burden due to the disease's chronic nature and limited medication half-life. AREAS COVERED: This review summarizes innovative therapeutics and delivery methods for nAMD. Emerging methods for extended drug delivery include high molar concentration anti-VEGF drugs, intravitreal sustained release devices, reservoirs for intravitreal delivery, and gene therapy biofactories. In addition to VEGF-A, therapies targeting inhibition of VEGF-C and D, the angiopoetin-2 (Ang-2)/Tie-2 pathway, tyrosine kinases, and integrins are reviewed. EXPERT OPINION: The evolving therapeutic landscape of nAMD is rapidly expanding our toolkit for effective and durable treatment. Recent FDA approvals of faricimab (Vabysmo) and high dose aflibercept (Eylea HD) for nAMD with potential extension of injection intervals up to four months have been promising developments for patients and providers alike. Further research and innovation, including novel delivery techniques and pharmacologic targets, is necessary to validate the efficacy of developing therapeutics and characterize real-world outcomes. demonstrating promise in expanding treatment durability.

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

PURPOSE: 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. TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry ( http://www.umin.ac.jp/ ; R000050688 UMIN 000044374).

Switching from a Fixed Monthly Aflibercept Regimen to Bi-Monthly Brolucizumab in Refractory Cases of Neovascular Age-Related Macular Degeneration.

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.

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.

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.

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.

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.

Real-world evidence for brolucizumab efficacy in age-related macular degeneration and central serous chorioretinopathy patients.

Real-world studies concerning different populations are valuable and bring new information regarding different regimens of Brolucizumab injections and their adverse reactions. The present study investigates the efficacy of a pro-re-nata regimen (PRN) for neovascular Age-related Macular Degeneration (nAMD). Separate from the main statistics we report the use of Brolucizumab in central serous chorioretinopathy (CSC). A retrospective observational single-center study was conducted on 82 eyes treated with Brolucizumab between 2021 and 2023, for nAMD. Patients were injected at intervals of at least 2 months after the loading phase. In 9 (3-20) months follow-up, only 0.26 % adverse reactions were noticed, with good resolution of retinal fluid (significant reduction of CST on SD-OCT, -72.50µ, p < 0.05), especially for subretinal fluid. 54 % of the eyes remained fluid-free. The interval of injection (INTOI, a parameter calculated by averaging the results of the division of the follow-up period to the number of injections received by each patient) was 2.68 (corresponding to an injection interval of 11 weeks). This could become an important parameter for the characterization of Brolucizumab and any other anti-VEGF therapy and could provide a more precise interval of injection in the future. Four patients also received Brolucizumab for the treatment of chronic CSC (3 doses each). All showed good response, 3 of them remaining fluid-free.

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.

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.

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.

Comparative Study on Anti-VEGF in Wet Age-Related Macular Degeneration in the Setting Based on Lean Methodology from the Bari Intravitreal Injection Registry (BIVIR).

INTRODUCTION: Optimizing treatment protocols for wet age-related macular degeneration (wAMD) is an ongoing challenge, as it involves a delicate balance between achieving therapeutic efficacy and minimizing invasive procedures' frequency. This study aimed to apply the Lean methodology and evaluate the effectiveness of this new setting on intravitreal therapy for wAMD, employing different anti-vascular endothelial growth factors (VEGF) drugs (bevacizumab, brolucizumab, aflibercept, ranibizumab), drawing data from the Bari Intravitreal Injections Registry (BIVIR). METHODS: This was a retrospective, monocentric, nonrandomized, comparative study. Lean methodology was employed to design the new setting and the BIVIR collected information from electronic medical records. Clinical data of four groups, stratified based on the first-line anti-VEGF agents used, were compared. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) changes were compared between the four groups at 3 and 12 months. RESULTS: Out of 4990 eyes and 41,323 intravitreal injections (IVs) recorded in BIVIR, 1421 eyes of 1182 patients were included. The mean number of IVs in first year was 6.1 ± 2.5, with no significant differences among the four subgroups. The mean change in BCVA was + 6.2 letters [95% confidence interval (CI) 5.6-6.8] after two IVs, and + 5.9 (95% CI 5.1-6.8) letters after three IVs; at three months, brolucizumab was associated with a greater mean increase in BCVA than bevacizumab (p = 0.050); aflibercept (p = 0.044) and ranibizumab p = 0.047). At the 1-year follow-up, the mean change was + 6.3 letters (95% CI 5.4-7.2), brolucizumab and ranibizumab were associated with a superior improvement in BCVA compared to aflibercept (p = 0.033). Regarding the CRT, a significant reduction was observed in the subgroup treated with brolucizumab at the 3-month follow-up, compared to bevacizumab (p = 0.003), aflibercept (p = 0.015), and ranibizumab (p < 0.001); Aflibercept exhibited a superior effect than ranibizumab (p = 0.001). At 1-year follow-up, aflibercept resulted in a more significant reduction of macular thickness compared to ranibizumab (p = 0.016) while no significant differences were observed among the other drugs. CONCLUSIONS: Our practical experience showed the effectiveness of the new setting in the treatment of wAMD. This comparative study at 1 year suggested a predominant brolucizumab efficacy on functional outcomes. In addition, brolucizumab and aflibercept appeared to have similar efficacy in fluid control.

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.

Brolucizumab effectiveness in pigment epithelium detachment due to exudative AMD in naïve treatment or non-responder patients.

PURPOSE: To investigate outcomes after Brolucizumab injection in naïve treatment or non-responder patients with exudative age-related macular degeneration (AMD). METHODS: It is a retrospective, comparative, cohort study conducted at the tertiary referral center of the University Hospital Polyclinic of Bari, for 5 years, from November 2017 until May 2022. 41 eyes with wet-AMD (w-AMD) were included, undergoing anti-vascular endothelial growth factor (VEGF) intravitreal injections. The sample was divided into two groups, the Bro-Switch group, and the Bro-Naïve group. The Bro-Switch group previously received a slot of other anti-VEGF intravitreal drugs. The Bro-Naïve group received Brolucizumab (Bro) as the first treatment. The pigment epithelium detachment (PED) and the best-corrected visual acuity (BCVA) outcomes before and after Bro-injection were evaluated. RESULTS: A significant reduction in PED measurement was registered in all eyes treated with Bro-injection (p = 0.35). The Bro-Naïve group improved better in PED measurement (mean difference: 297.92 ± 72,32) as compared to the Bro-Switch group (mean difference: 185.06 ± 11.07). On the contrary, no significant reduction in BCVA in the two groups was recorded (p = 0.66). CONCLUSION: We suggest Bro-injection for w-AMD as effective anatomical outcomes in PED flattening, but not similar in visual results. Although this study evaluated short-term outcomes, the hopeful results can lead to interesting medium-long time effects.

Angioid Streaks Remain a Challenge in Diagnosis, Management, and Treatment.

Aim: Angioid streaks (ASs) are a rare retinal condition and compromise visual acuity when complicated with choroidal neovascularization (CNV). They represent crack-like dehiscences at the level of the Bruch's membrane. This objective narrative review aims to provide an overview of pathophysiology, current treatment modalities, and future perspectives on this condition. Materials and Methods: A literature search was performed using "PubMed", "Web of Science", "Scopus", "ScienceDirect", "Google Scholar", "medRxiv", and "bioRxiv." Results: ASs may be idiopathic, but they are also associated with systemic conditions, such as pseudoxanthoma elasticum, hereditary hemoglobinopathies, or Paget's disease. Currently, the main treatment is the use of anti-vascular endothelial growth factors (anti-VEGF) to treat secondary CNV, which is the major complication observed in this condition. If CNV is detected and treated promptly, patients with ASs have a good chance of maintaining functional vision. Other treatment modalities have been tried but have shown limited benefit and, therefore, have not managed to be more widely accepted. Conclusion: In summary, although there is no definitive cure yet, the use of anti-VEGF treatment for secondary CNV has provided the opportunity to maintain functional vision in individuals with AS, provided that CNV is detected and treated early.

Sustained Disease Control in DME Patients upon Treatment Cessation with Brolucizumab.

Background: Treatment cessation due to a dry retina has not been systematically addressed in diabetic macular edema (DME). In three out of four patients receiving 6 mg of brolucizumab in the KITE study, treatment was terminated after the study ended. Methods: The KITE study was a double-masked, multicenter, active-controlled, randomized trial (NCT03481660) in DME patients. Per protocol, patients received five loading injections of Brolucizumab at 6-week intervals, with the option to adjust to 8 weeks in case of disease activity or to extend in the second year to a maximum of 16 weeks in the absence of retinal fluid. Results: After two years, one patient required eight weekly injections, while three patients reached a maximal treatment interval of 16 weeks. The severity of diabetic retinopathy improved in all patients with no dye leakage according to fluorescein angiography (FA) and no retinal fluid according to OCT in three patients. Treatment was paused in these three patients for >36 months, while the fourth patient required continuous treatment at 5-week intervals after switching to other licensed anti-VEGF agents. Conclusions: The adoption of treatment according to individual needs, including considering treatment cessation, may contribute to improved treatment adherence in many patients and be more frequently possible than expected.

Real-World Experience with Brolucizumab Compared to Aflibercept in Treatment-Naïve and Therapy-Refractory Patients with Diabetic Macular Edema.

Background: To report on the outcome of intravitreal brolucizumab compared to aflibercept in patients with diabetic macular edema (DME). Methods: Prospective, observational, study in 35 eyes of 24 patients with a loading dose of five injections of 6 mg brolucizumab every 6 weeks (q6w, treatment-naïve eyes) or a minimum of two injections of brolucizumab q6w after the switch (recalcitrant DME eyes), followed by a treat and extend (T&E) regimen. The results were compared with 40 eyes of 31 DME patients who were treated with aflibercept. The data were obtained from the Berlin Macula Registry. The primary outcome measure was the change in best-corrected visual acuity (BCVA) at week 36. Secondary outcome measures were the change in central retinal thickness (CRT) and the treatment intervals until week 36. Results: BCVA increased significantly in treatment-naïve DME eyes treated with either brolucizumab (+0.12 logMAR, +6.4 letters, p = 0.03) or aflibercept (+0.19 logMAR, +9.5 letters, p = 0.001). In recalcitrant DME eyes, BCVA also increased significantly after switching to brolucizumab (+0.1 logMAR, +5 letters, p = 0.006) or aflibercept (+0.11 logMAR, +5.5 letters, p = 0.02). All treatment-naïve and recalcitrant DME eyes had a significant decrease in CRT after treatment with brolucizumab (p = 0.001 and p < 0.001) or aflibercept (p = 0.0002 and p = 0.03). At week 36, the mean treatment interval for brolucizumab was 11.3 weeks, while for aflibercept, it was 6.5 weeks for treatment-naïve eyes and 9.3 weeks vs. 5.3 weeks for pretreated eyes. Conclusions: In routine clinical practice, patients with treatment-naïve and recalcitrant DME showed a favorable response to brolucizumab and aflibercept therapy, with a reduced injection frequency after brolucizumab treatment.