Aflibercept Group Research Articles

Impact of Aflibercept vs Dexamethasone Treatment on Epiretinal Membrane Formation in Eyes with Diabetic Macular Edema.

This study aimed to investigate the impact of aflibercept and dexamethasone (DEX) on the formation of epiretinal membrane (ERM) and their treatment outcomes in eyes with diabetic macular edema (DME). In this retrospective cohort study, medical records of 124 eyes from 429 patients diagnosed with DME were reviewed between June 2017 and June 2019. Patients were categorized into two groups: the aflibercept group (67 eyes) and the DEX group (57 eyes). The primary endpoint was the secondary ERM incidence following intravitreal treatments and its correlation across different medications. Secondary endpoints included longitudinal changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT). Over a 24-month follow-up, eyes treated with DEX had approximately a fourfold higher incidence of ERM development compared to aflibercept [hazard ratio (HR) = 3.97, p = 0.02]. These eyes also showed worse BCVA (p = 0.059) and increased CMT (p = 0.004), despite requiring fewer total injections (p = 0.000) in the survival analysis model. The cumulative probability of ERM formation was 13.7%. Additionally, DME eyes exhibited poor functional and anatomical outcomes after developing ERM, while age, A1c level, DR severity, initial BCVA and CMT, lens status, and previous laser treatment were not associated with an elevated incidence of ERM formation. Intravitreal DEX implantation in DME eyes resulted in a higher incidence of secondary ERM formation compared to aflibercept over a 2-year period. The therapeutic efficacy for DME was diminished following ERM development, leading to worse anatomical outcomes. New therapeutic approaches should be explored to prevent ERM formation while maintaining both anatomical and functional outcomes in DME treatment.

BNT162b2 vaccine booster dose did not influence the activity of the exudative form of age-related macular degeneration during anti-vascular endothelial growth factor therapy.

Due to safety concerns, patients were hesitant to receive a booster dose of COVID-19 vaccine. In this study, we investigated whether neovascular age-related macular degeneration activity deteriorated after receiving the booster dose of the BNT162b2 vaccine. Optical coherence tomography (OCT) of the macula, best-corrected visual acuity (BCVA), and slit-lamp examination data were collected from 89 patients. All these individuals were diagnosed with neovascular age-related macular degeneration (AMD) and treated with intravitreal injections of aflibercept or ranibizumab. During the process of treatment, patients received a booster dose of the BNT162b2 vaccine. Time points included two visits before (marked as "-2", "-1") and two visits after (marked as "1", "2") the uptake of the booster dose. There were significant differences in the average thickness and total volume of the macula during follow-up. Moreover, a decreased average thickness, total volume, total thickness of the macula, subretinal fluid thickness, and subretinal complex thickness was observed between the time points "-2" and "2", but only in the aflibercept group. There were no significant differences in the frequency of occurring intraretinal cysts, subretinal fluid, serous retinal pigment epithelial detachments retinal hemorrhage, subretinal hyperreflective material, complete RPE and outer retinal atrophy, and BCVA before and after the booster dose. These results demonstrate that the BNT162b2 vaccine booster dose did not deteriorate the course of neovascular AMD.

Aflibercept Biosimilar MYL-1701P vs Reference Aflibercept in Diabetic Macular Edema

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

Efficacy and Safety of Efdamrofusp Alfa versus Aflibercept in Participants with Neovascular Age-Related Macular Degeneration: A Randomized, Double-Masked, Active-Controlled, Noninferiority, Phase II Trial

PurposeTo evaluate efficacy and safety of efdamrofusp alfa compared with aflibercept in neovascular age-related macular degeneration (nAMD). DesignRandomized, double-masked, multicenter, active-controlled, non-inferiority phase 2 study ParticipantsA total of 231 treatment-naïve and previously treated participants with active choroidal neovascularization secondary to nAMD were enrolled. MethodsEligible participants were randomized (1:1:1) to 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa or 2 mg aflibercept groups. Participants in all groups received three initial monthly loading doses, followed by treatment every 8 weeks with assessment every 4 weeks up to week 52. Main outcome measuresThe primary endpoint was the mean BCVA change from baseline to week 36. The pre-specified noninferiority margin was set as –5 letters (80% CI). ResultsEach treatment group included 77 participants. The mean BCVA changes from baseline to week 36 for 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa and aflibercept groups were +10.6, +11.4, +12.0 letters, respectively; Least Squares (LS) mean difference were –1.4 (80% CI: –3.5 to 0.7) between 2 mg efdamrofusp alfa and aflibercept, and –0.6 (80% CI: –2.7 to 1.6) between 4 mg efdamrofusp alfa and aflibercept. Mean central retinal thickness changes were consistent across groups. Adverse event rate was comparable among the groups. ConclusionsEfdamrofusp alfa demonstrated noninferiority to aflibercept in BCVA improvement, accompanied by a similar safety profile.

Three-month outcomes of treatment with faricimab or aflibercept for neovascular age-related macular degeneration: a propensity score matching study in a Japanese population.

This study aimed to compare the treatment outcomes of patients with neovascular age-related macular degeneration (nAMD) who initially received faricimab or aflibercept treatment using propensity score matching (PSM) to align patient backgrounds. Patients with treatment-naïve nAMD who received either faricimab or aflibercept for three consecutive monthly injections as the loading phase were enrolled in this study. In the 1:1 PSM, sex, age, best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), and AMD subtypes in the pre-treatment state were selected as covariates. We examined the BCVA, CMT, CCT, and remaining fluid at 1-, 2-, and 3-month after the first injection. After PSM, 43 eyes were included in the faricimab and aflibercept group each. Both groups showed significant improvements in BCVA, CMT, and CCT at 1-, 2-, and 3-month after the initial injection compared with baseline. Meanwhile, no significant differences were observed between the two groups at any time point regarding BCVA, CMT, and CCT. At 1-month, 18.6% of patients in the faricimab group and 41.9% in the aflibercept group demonstrated residual subretinal fluid or intraretinal fluid, with a significant difference between the groups (P = 0.03). The BCVA improved after three loading injections of both faricimab and aflibercept. Faricimab may provide a favorable early treatment response in reducing subretinal fluid in a Japanese cohort.

Comparison of the efficacy and safety of SCD411 and reference aflibercept in patients with neovascular age-related macular degeneration

To compare the efficacy and safety of the proposed aflibercept biosimilar SCD411 and reference aflibercept in patients with neovascular age-related macular degeneration, this randomized, double-masked, parallel-group, multicenter study was conducted in 14 countries from 13 August 2020 to 8 September 2022. Patients with neovascular age-related macular degeneration. With subfoveal, juxtafoveal, or extrafoveal choroidal neovascularization were aged 50 years or older. Intravitreal injection of SCD411 or aflibercept (2.0 mg) were administered every 4 weeks for the first three injections and every 8 weeks until week 48. The primary efficacy endpoint was the change in best-corrected visual acuity from baseline to week 8 with an adjusted equivalence margin of ± 3.0 letters. Patients were randomly assigned to receive either SCD411 (n = 288) or reference aflibercept (n = 288). A total of 566 participants (98.3%) completed week 8 of the study. The least-squares mean difference of change in best-corrected visual acuity from baseline to week 8 (SCD411—aflibercept) was − 0.4 letters (90% confidence interval = − 1.6 to 0.9). The incidence of ocular (69 of 287 [24.0%] vs. 71 of 286 [24.8%]) and serious ocular (5 of 287 [1.7%] vs. 3 of 286 [1.0%]) treatment-emergent adverse effects were similar between the SCD411 and aflibercept groups. Immunogenicity analysis revealed a low incidence of neutralizing antibody formation in both groups. In conclusion, SCD411 has equivalent efficacy compared with reference aflibercept in patients with neovascular age-related macular degeneration and has a comparable safety profile. The results support the potential use of SCD411 for the treatment of neovascular age-related macular degeneration.

Biosimilar Candidate CT-P42 in Diabetic Macular Edema: 24-Week Results from a Randomized, Active-Controlled, Phase III Study

ObjectiveTo demonstrate the therapeutic similarity of CT-P42 compared to reference aflibercept (Eylea®) in adult patients with diabetic macular edema (DME). DesignRandomized, active-controlled, double-masked, Phase III clinical trial ParticipantsPatients with a diagnosis of either type 1 or 2 diabetes mellitus (DM) with DME involving the center of the macula. MethodsPatients were randomized (1:1) to receive either CT-P42 or reference aflibercept (2 mg/0.05 mL) by intravitreal injection every 4 weeks (5 doses) then every 8 weeks (4 doses) in the main study period. Results up to Week 24 are reported herein. Main Outcome MeasuresThe primary endpoint was mean change from baseline at Week 8 in best corrected visual acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Equivalence between CT-P42 and reference aflibercept was to be concluded if the two-sided 95% confidence interval (CI) (global assumptions) and two-sided 90% CI (US Food and Drug Administration [FDA] assumptions) for the treatment difference fell entirely within the equivalence margin of ±3 letters, as assessed in the full analysis set. ResultsOverall, 348 patients were randomized (CT-P42: 173; reference aflibercept: 175). BCVA improved from baseline to Week 8 in both groups, with a least squares mean (standard error) improvement of 9.43 (0.798) and 8.85 (0.775) letters in the CT-P42 and reference aflibercept groups, respectively. The estimated between-group treatment difference was 0.58 letters, with the CIs within the pre-defined equivalence margin of ±3 letters (95% CI −0.73, 1.88 [global]; 90% CI −0.52, 1.67 [FDA]). Through Week 24, other efficacy results for the two groups, in terms of change in BCVA and retinal central subfield thickness, as well as ETDRS Diabetic Retinopathy Severity Scale score, supported therapeutic similarity. Pharmacokinetics, usability, safety (including the proportions of patients experiencing at least one treatment-emergent adverse event [CT-P42: 50.3%; reference aflibercept: 53.7%]), and immunogenicity were also comparable between groups. ConclusionsThis study in patients with DME demonstrated equivalence between CT-P42 and reference aflibercept (2 mg/0.05 mL) in terms of efficacy, with similar pharmacokinetic, usability, safety, and immunogenicity profiles.

Intravitreal Aflibercept vs Laser Therapy for Retinopathy of Prematurity

Prospective long-term data after retinopathy of prematurity (ROP) treatment with anti-vascular endothelial growth factor injections vs laser therapy are scarce. The FIREFLEYE (Aflibercept for ROP IVT Injection vs Laser Therapy) next trial is prospectively evaluating the long-term efficacy and safety outcomes following ROP treatment with intravitreal aflibercept vs laser therapy. To evaluate 2-year ophthalmic and safety outcomes after 0.4-mg aflibercept injection or laser therapy in the 24-week randomized (2:1) FIREFLEYE trial (FIREFLEYE outcomes previously reported). This prospective nonrandomized controlled trial performed in 24 countries in Asia, Europe, and South America (2020-2025) follows up participants treated in the FIREFLEYE randomized clinical trial (2019-2021) through 5 years of age. Participants included children born very or extremely preterm (gestational age ≤32 weeks) or with very or extremely low birth weight (≤1500 g) who were previously treated with a 0.4-mg injection of aflibercept compared with laser therapy for severe acute-phase ROP. Data for the present interim analysis were acquired from March 18, 2020, to July 25, 2022. Complications of ROP treated at investigator discretion (no study treatment). Efficacy end points included ROP status, unfavorable structural outcomes, ROP recurrence, treatment for ROP complications, completion of vascularization, and visual function. Safety end points included adverse events and growth and neurodevelopmental outcomes. Overall, 100 children were enrolled (median gestational age, 26 [range, 23-31] weeks; 53 boys and 47 girls). Of these, 21 were Asian, 2 were Black, 75 were White, and 2 were of more than 1 race. At 2 years of age, 61 of 63 children (96.8%) in the aflibercept group vs 30 of 32 (93.8%) in the laser group had no ROP. Through 2 years of age, 62 of 66 (93.9%) in the aflibercept group and 32 of 34 (94.1%) in the laser group had no unfavorable structural outcomes. No new retinal detachment occurred during the study. Four children in the aflibercept group (6.1%) were treated for ROP complications before 1 year of age (2 had preexisting end-stage disease and total retinal detachment; 1 had reactivated plus disease; and 1 had recurrent retinal neovascularization not further specified). Most children were able to fix and follow a 5-cm toy (aflibercept group, 118 of 122 eyes [96.7%] among 63 children; laser group, 62 of 63 eyes [98.4%] among 33 children). High myopia was present in 9 of 115 eyes (7.8%) among 5 children in the aflibercept group and 13 of 60 eyes (21.7%) among 9 children in the laser group. No relevant differences in growth and neurodevelopmental outcomes by Bayley Scales of Infant and Toddler Development, Third Edition and Vineland Adaptive Behavior Scales, Second Edition were identified. In this nonrandomized follow-up of a randomized clinical trial comparing treatment of severe acute-phase ROP with 0.4-mg injection of aflibercept and laser, disease control was stable and visual function was appropriate in children through 2 years of age. No adverse effects on safety, including growth and neurodevelopment, were identified. These findings provide clinically relevant long-term information on intravitreal aflibercept injection therapy for ROP. ClinicalTrials.gov Identifier: NCT04015180.

Aflibercept combined with triamcinolone acetonide in the treatment of diabetic macular edema: optical coherence tomography and optical coherence tomography angiography.

To analyze the relationship between optical coherence tomography (OCT) and OCT angiography (OCTA) imaging in patients with diabetic macular edema (DME) who are treated with a combination of aflibercept and triamcinolone acetonide (TA). A total of 76 eyes newly diagnosed DME were included in this study. They were randomly assigned to receive either aflibercept or a combination of aflibercept and TA. Injections once a month for a total of three injections. Central macular thickness (CMT), number of hyperreflective foci (HRF), height of subretinal fluid (SRF), and area of foveal avascular zone (FAZ) were evaluated using OCT and OCTA at baseline and after each monthly treatment. Both groups showed improvement in best corrected visual acuity (BCVA) and reduction in macular edema after treatment, and the difference in BCVA between the two groups was statistically significant after each treatment (P<0.05). The difference in CMT between the two groups was statistically significant after the first two injections (P<0.01), but not after the third injection (P=0.875). The number of HRF (1mo: 7.41±8.25 vs 10.86±7.22, P=0.027; 2mo: 5.33±6.13 vs 9.12±8.61, P=0.034; 3mo: 3.58±3.00 vs 6.37±5.97, P=0.007) and height of SRF (1mo: 82.39±39.12 vs 105.77±42.26 µm, P=0.011; 2mo: 36.84±10.02 vs 83.59±37.78 µm, P<0.01; 3mo: 11.57±3.29 vs 45.43±12.60 µm, P<0.01) in combined group were statistically significant less than aflibercept group after each injection, while the area of FAZ showed no significant change before and after treatment in both groups. The combination therapy of aflibercept and TA shows more significant effects on DME eyes with decreased HRF and SRF. However, both aflibercept and combination therapy show no significant change in the area of FAZ.

Анализ динамики толщины хрусталика на фоне интравитреального введения афлиберцепта и депо дексаметазона

Antiangiogenic therapy is the main method of choice in the treatment of a number of retinal diseases. IVI injections with an anti-VEGF drug, as well as IVV implants of dexamethasone ozurdex, were widely used. Considering that currently the effect of these drugs on cataractogenesis is poorly understood, work in this direction is strategically important for understanding the morphological features of the development of cataracts of a post-injection etiological nature. Objective. To study the dynamics of lens thickness against the background of intravitreal administration of aflibercept and dexamethasone depot. Material and methods. 220 eyes were included in the study. Depending on the drug used, the first group included 100 eyes that received IVI of aflibercept, the second group included 20 eyes that received an intravitreally injected deхamethasone ozurdex implant, the control (third) group consisted of 100 eyes. Results. The dynamics of changes in lens thickness was recorded in the groups of patients who received Ozurdex between 3 and 6 months (0.012), which reflects a slow increase in lens thickness in this group. Conclusion. In patients who received aflibercept, there was no statistically significant difference in lens thickness after 3 and 6 months. In the dexamethasone depot group, a statistically significant increase in lens thickness was noted at 3 and 6 months compared with the control group and the aflibercept group. Keywords: intravitreal administration of aflibercept, antiangiogenic therapy, lens thickness

The effect of antiangiogenic agent aflibercept on surgically induced endometriosis in a rat model.

The aim of the study is to show for the first time how aflibercept affects endometriosis lesions. Surgically induced endometriosis in Wistar albino female rats. Rats with endometriosis were randomly divided into three groups: control (Co), aflibercept (Af), and leuprolide acetate (Le). Then, Af, aflibercept, and Le received leuprolide acetate. The control group was not treated. The weights and changes in intra-abdominal adhesions of the rats before and after treatment were recorded according to the Blauer adhesion score. Blood extracted for sacrifice was analyzed. Endometriotic lesions were evaluated for size, volume, histology, and immunohistochemistry (vascular endothelial growth factor [VEGF] and CD31). Significance level was accepted as p < 0.05. Aflibercept significantly reduced endometrial implant volume (p = 0.002). The explant epithelial histological score showed a significant difference between aflibercept and leuprolide acetate (p = 0.006) and between aflibercept and control groups (p = 0.002). Aflibercept decreased VEGF-H and CD31 expression (p = 0.001) more than leuprolide acetate. Aflibercept improved adhesions (p = 0.006). Aflibercept is more successful than leuprolide acetate in the treatment of endometriosis.

Kavain Alleviates Choroidal Neovascularization Via Decreasing the Activity of the HIF-1α/VEGF-A/VEGFR2 Signaling Pathway and Inhibiting Inflammation.

Neovascular age-related macular degeneration (nAMD) is a prevalent cause of blindness in the elderly. Standard treatment includes anti-vascular endothelial growth factor (anti-VEGF) drugs, such as aflibercept. However, anti-VEGF drugs may have limited efficacy and cause drug resistance. This study explores whether Kavain, an anti-inflammatory molecule from Piper methysticum, can treat choroidal neovascularization (CNV). Various experiments were conducted to assess the Kavain's toxicity. The impact of Kavain on in vitro cultured endothelial cells was examined through 5-ethynyl-20-deoxyuridine (EdU) assays, transwell migration assays, and tube formation assays. The therapeutic effects of Kavain on CNV were investigated using a laser-induced CNV mice model. To elucidate the mechanism of Kavain, network pharmacology analysis, molecular docking, and western blots were performed. Kavain exhibited no apparent toxicity both in vitro and in vivo. Kavain significantly decreased endothelial cell viability, proliferation, migration, and tube formation ability in a dose-dependent manner compared to the hypoxia groups (P<0.05). Kavain alleviated CNV in the laser-induced CNV mouse model compared to the control groups (P<0.05). These effects were statistically significantly enhanced in the Kavain plus aflibercept groups (P<0.05). Following Kavain administration, the expression levels of various inflammatory factors were markedly reduced in retinal pigment epithelium (RPE)/choroid complexes (P<0.05). Mechanistically, Kavain decreased the activity of the hypoxia-inducible factor 1α (HIF-1α)/VEGF-A/ VEGF receptor 2 (VEGFR2) signaling pathway. Our study is the first to demonstrate Kavain's potential as a promising treatment for nAMD, owing to its dual effects of anti-inflammation and anti-angiogenesis.

Comparison of ranibizumab, aflibercept, and dexamethasone implant monotherapy in treatment-naive eyes with diabetic macular edema: A 12-month real-life experience.

To compare the functional and anatomical outcomes of ranibizumab, aflibercept, and dexamethasone implant monotherapy in treatment-naive eyes with diabetic macular edema (DME) in real-life conditions. In this retrospective cohort study, data were obtained from the hospital database of treatment-naive patients diagnosed with DME with at least 12 months of follow-up. Best corrected visual acuity (BCVA) and central retinal thickness (CRT) at baseline, third month, sixth month, ninth month, and 12th month were recorded. In addition, a subgroup analysis was performed based on having good (below 0.4 log of minimum angle of resolution [logMAR]) or poor (0.4 logMAR and above) vision. A total of 219 eyes of 142 patients were included in the study. The change in the mean BCVA from baseline to 12th month was from 0.62 logMAR to 0.42 logMAR (P < 0.001) in the ranibizumab group, from 0.56 logMAR to 0.39 logMAR (P < 0.001) in the aflibercept group, and from 0.46 logMAR to 0.5 logMAR (P = 0.653) in the dexamethasone group. There was no significant difference between the treatment groups at any time point (P > 0.05). The mean amount of CRT change was statistically significant at 12 months in all groups (ranibizumab: -175.4 µm, aflibercept: -153.3 µm, dexamethasone: -71.4 µm) (P < 0.05). In eyes with initially good vision, the final BCVA at 12 months was significantly better in the ranibizumab group compared to the dexamethasone group (P = 0.008). The aflibercept group had better visual acuity than the dexamethasone group, but there was no statistically significant difference (P = 0.059). There was no significant difference in final BCVA in eyes with initially poor vision. No serious ocular/systemic complications were noted. At the 12th month, a significant decrease in CRT was achieved in all treatment groups, whereas only ranibizumab and aflibercept groups had a significant BCVA increase. In eyes with initially good vision, the final BCVA at 12 months was better in the ranibizumab group compared to the dexamethasone group, whereas it was similar in all groups having initially poor vision.

Effect of aflibercept combined with triamcinolone acetonide on aqueous humor growth factor and inflammatory mediators in diabetic macular edema.

To investigate the efficacy of aflibercept combined with sub-tenon injection of triamcinolone acetonide (TA) in treating diabetic macular edema (DME) and to examine changes in growth factors and inflammatory mediator levels in aqueous humor after injection. Totally 67 DME patients (67 eyes) and 30 cataract patients (32 eyes) were enrolled as the DME group and the control group, respectively. The DME group was divided into the aflibercept group (34 cases) and the aflibercept combined with TA group (combined group, 33 cases). The aqueous humor of both groups was collected during the study period. The aqueous levels of vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β) were detected using a microsphere suspension array technology (Luminex 200TM). Aqueous cytokines, best-corrected visual acuity (BCVA), central macular thickness (CMT), and complications before and after treatment were compared between the aflibercept group and combined group. The concentrations of VEGF, MCP-1, IL-6, and IL-8 in the aqueous humor were significantly higher in the DME group than those of the control group (all P<0.01). After 1mo of surgery, the concentrations of VEGF, MCP-1, IL-6, and IL-8 in the aqueous humor were significantly lower in the combined group than those of the aflibercept group (all P<0.01). The BCVA and CMT values of the two groups were statistically different after 1 and 2mo of treatment (P<0.01). However, the difference was not statistically significant after 3mo of treatment (P>0.05). The cytokines VEGF, MCP-1, IL-6, and IL-8 in the aqueous humor of DME patients are significantly increased. Aflibercept and aflibercept combined with TA have good efficacy in DME patients, can effectively reduce CMT, improve the patient's vision, and have high safety. Aflibercept combined with TA can quickly down-regulate the aqueous humor cytokines and help to relieve macular edema rapidly. However, the long-term efficacy is comparable to that of aflibercept alone.

Choroidal remodeling following different anti-VEGF therapies in neovascular AMD

The purpose of this study was to investigate choroidal morphology remodeling in AMD-associated type 1 macular neovascularization using two different anti-VEGF drugs. We registered 73 treatment-naïve eyes with a diagnosis of exudative AMD and type 1 MNV. Patients received 3 monthly intravitreal aflibercept (n = 36, aflibercept group [AG]) or brolucizumab (n = 37, brolucizumab group [BG]). Baseline best-corrected visual acuity (BCVA) and anatomical (structural optical coherence tomography) parameters were collected at “T1 control”, before the loading phase (LP) of intravitreal injection, and at “T2 control”, 1 month after the last injection. The main outcomes measured were choroidal vascularity index (CVI), sub-foveal choroidal thickness (SFCT), and central macular thickness (CMT). Our results displayed significant SFCT reduction in both groups between T1 and T2 (p < 0.05), We did not find choroidal vascularity modifications (p > 0.05) after the loading aflibercept injections. Moreover, only the BG displayed a significant choroidal remodeling (stromal choroidal area [SCA], total choroidal area [TCA] and CVI) at T2 (p < 0.05). In particular, a relevant stromal and total choroidal volume reduction was noted, accompanied by an increase in CVI. To conclude, the latter modifications of the choroidal morphology were found significant between two groups (p < 0.05). Our analysis showed a significant impact of brolucizumab on choroidal morphology in eyes affected by type 1 nAMD. This effect was found relevant when compared with aflibercept.

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

To compare the efficacy of brolucizumab, half-dose PDT, and aflibercept in treating chronic central serous chorioretinopathy (CSC). 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). 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. 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.

Aflibercept or ranibizumab for diabetic macular edema.

Vascular endothelial growth factor (VEGF) is the primary substance involved in retinal barrier breach. VEGF overexpression may cause diabetic macular edema (DME). Laser photocoagulation of the macula is the standard treatment for DME; however, recently, intravitreal anti-VEGF injections have surpassed laser treatment. Our aim was to evaluate the efficacy of intravitreal injections of aflibercept or ranibizumab for managing treatment-naive DME. This single-center, retrospective, interventional, comparative study included eyes with visual impairment due to treatment-naive DME that underwent intravitreal injection of either aflibercept 2 mg/0.05 mL or ranibizumab 0.5 mg/0.05 mL at Al-Azhar University Hospitals, Egypt between March 2023 and January 2024. Demographic data and full ophthalmological examination results at baseline and 1, 3, and 6 months post-injection were collected, including the best-corrected distance visual acuity (BCDVA) in logarithm of the minimum angle of resolution (logMAR) notation, slit-lamp biomicroscopy, dilated fundoscopy, and central subfield thickness (CST) measured using spectral-domain optical coherence tomography. Overall, the 96 eyes of 96 patients with a median (interquartile range [IQR]) age of 57 (10) (range: 20-74) years and a male-to-female ratio of 1:2.7 were allocated to one of two groups with comparable age, sex, diabetes mellitus duration, and presence of other comorbidities (all P >0.05). There was no statistically significant difference in baseline diabetic retinopathy status or DME type between groups (both P >0.05). In both groups, the median (IQR) BCDVA significantly improved from 0.7 (0.8) logMAR at baseline to 0.4 (0.1) logMAR at 6 months post-injection (both P = 0.001), with no statistically significant difference between groups at all follow-up visits (all P >0.05). The median (IQR) CST significantly decreased in the aflibercept group from 347 (166) µm at baseline to 180 (233) µm at 6 months post-injection, and it decreased in the ranibizumab group from 360 (180) µm at baseline to 190 (224) µm at 6 months post-injection (both P = 0.001), with no statistically significant differences between groups at all follow-up visits (all P >0.05). No serious adverse effects were documented in either group. Ranibizumab and aflibercept were equally effective in achieving the desired anatomical and functional results in patients with treatment-naïve DME in short-term follow-up without significant differences in injection counts between both drugs. Larger prospective, randomized, double-blinded trials with longer follow-up periods are needed to confirm our preliminary results.

Choroidal thickness after anti‐vascular endothelial growth factor in treatment‐naïve typical neovascular age‐related macular degeneration patients: A systematic review and meta‐analysis

Aims/Purpose: To evaluate the effect of anti‐vascular endothelial growth factor (anti‐VEGF) on choroidal thickness (CT) in treatment‐naïve typical neovascular age‐related macular degeneration (AMD) patients during the loading phase.Methods: A systematic literature search was conducted in CENTRAL, MEDLINE, EMBASE, Scopus, Web of Science, Clinical Trials, ICTRP and ISRCTN from inception to October 19, 2022. The protocol was registered with PROSPERO (CRD42022371192). We included both retrospective and prospective randomized controlled trials, cohort studies, case control and case series of typical neovascular AMD patients. Studies with polypoidal choroidal vasculopathy or unclear diagnoses and reports in other languages than English were excluded. Risk of bias was assessed using critical appraisal tools provided by Joanna Briggs Institute.Results: 43 studies were included in the review. Meta‐analysis of all studies reporting sufficient data and simultaneously disregarding measurement technique, macular neovascularization (MNV) type and anti‐VEGF type, yielded a significant decrease of CT with anti‐VEGF treatment. To decrease bias, sub‐analyses for Type 1 and 2 MNV sorted by anti‐VEGF type found a significant effect for both aflibercept and ranibizumab, and the effect appears greater in the aflibercept group. For Type 3 MNV, the baseline CT was generally thinner and the decrease more modest.Conclusions: Anti‐VEGF drugs decrease CT in typical neovascular AMD. There is a greater effect of aflibercept compared to ranibizumab. For bevacizumab and brolucizumab there are few studies, but available data show a tendency of greater effect in the latter. There are low numbers of randomized trials on the topic and publication bias might affect the results. More studies randomized to treatment of patients with a thin baseline choroid should be conducted.

Efficacy and Safety of Biosimilar QL1207 vs. the Reference Aflibercept for Patients with Neovascular Age-Related Macular Degeneration: A Randomized Phase 3 Trial.

This trial aimed to compare the efficacy and safety between biosimilar QL1207 and the reference aflibercept for the treatment of neovascular age-related macular degeneration (nAMD). This randomized, double-blind, phase 3 trial was conducted at 35 centers in China. Patients aged ≥ 50years old with untreated subfoveal choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) letter score of 73-34 were eligible. Patients were randomly assigned to receive intravitreous injections of QL1207 or aflibercept 2mg (0.05ml) in the study eye every 4weeks for the first 3months, followed by 2mg every 8weeks until week 48, stratified by baseline BCVA ≥ or < 45 letters. The primary endpoint was BCVA change from baseline at week 12. The equivalence margin was ± 5 letters. The safety, immunogenicity, pharmacokinetics (PK), and plasma vascular endothelial growth factor (VEGF) concentration were also evaluated. A total of 366 patients were enrolled (QL1207 group, n = 185; aflibercept group, n = 181) from Aug 2019 to Jan 2022 with comparable baseline characteristics. The least-squares mean difference in BCVA changeswas - 1.1 letters(95% confidence interval - 3.0 to 0.7; P = 0.2275) between the two groups, within the equivalence margin. The incidences of treatment-emergent adverse events (TEAE; QL1207: 71.4% [132/185] vs. aflibercept: 71.8% [130/181]) and serious TEAE (QL1207: 14.1% [26] vs. aflibercept: 12.7% [23]) appeared comparable between treatment groups, and no new safety signal was found. Anti-drug antibody, PK profiles, and VEGF concentration were similar between the two groups. QL1207 has equivalent efficacy to aflibercept for nAMD with similar safety profiles. It could be used as an alternative anti-VEGF agent for clinical practice. ClinicalTrials.gov: NCT05345236 (retrospectively registered on April 25, 2022); National Medical Products Administration of China: CTR20190937 (May 20, 2019).

Changes in activity impairment and work productivity after treatment for vitreous hemorrhage due to proliferative diabetic retinopathy: Secondary outcomes from a randomized controlled trial (DRCR Retina Network Protocol AB).

Vitreous hemorrhage from proliferative diabetic retinopathy can cause severe vision loss. DRCR Retina Network Protocol AB was a randomized clinical trial comparing intravitreal aflibercept versus vitrectomy with panretinal photocoagulation and found no difference in the average rate of visual recovery over 104 weeks. Herein, we describe patient-reported outcome measures from Protocol AB. Secondary analysis of a multicenter (39 sites) randomized clinical trial. The Work Productivity and Activity Impairment Questionnaire was administered at 4, 12, 24, 36, 52, 68, 84, and 104 weeks. Main outcomes were mean change in activity impairment and work productivity loss over 24 and 104 weeks (area under the curve). Mean (SD) activity impairment at baseline was 58% (27%) in the aflibercept group (N = 99) and 56% (30%) in the vitrectomy group (N = 105). The mean reduction in activity impairment from baseline over 24 weeks was 21% (25%) in the aflibercept group and 27% (31%) in the vitrectomy group (adjusted difference = -6.8% [95% CI, -12.7% to -0.9%], P = .02); over 104 weeks, the adjusted mean difference was -3.1% (95% CI, -9.2% to 3.0%, P = .31). Mean work productivity loss at baseline was 51% (28%) in the aflibercept group (N = 44) and 58% (30%) in the vitrectomy group (N = 43). The mean reduction in work productivity loss from baseline over 24 weeks (area under the curve) was 19% (23%) in the aflibercept group and 31% (24%) in the vitrectomy group (adjusted difference = -8.3% [95% CI, -16.8% to 0.2%], P = .06); over 104 weeks, the adjusted mean difference was -9.1% (95% CI, -18.4% to 0.2%, P = .05). Participants with vitreous hemorrhage from proliferative diabetic retinopathy had less activity impairment over 24 weeks when treated initially with vitrectomy and panretinal photocoagulation versus intravitreal aflibercept. The trend was similar for work productivity but not statistically significant. By 104 weeks, the improvements were similar in the two treatment groups. ClinicalTrials.gov NCT02858076.