Aflibercept Group Research Articles

Comparison of intravitreal aflibercept and dexamethasone implant in the treatment of macular edema associated with diabetic retinopathy or retinal vein occlusion: a Meta-analysis and systematic review.

To compare the efficacy and safety of intravitreal aflibercept with dexamethasone implant in the treatment of macular edema (ME) associated with diabetic retinopathy (DR) or retinal vein occlusion (RVO). A comprehensive search of studies comparing dexamethasone and aflibercept in patients with ME was conducted at PubMed, Embase, and Cochrane Central Register of Controlled Trials from the beginning of library to April 16, 2021. Extracting the data including best-corrected visual acuity (BCVA), central retinal thickness (CRT), number of injections and serious adverse events (SAEs) from the final qualified articles. RevMan 5.3 software was used for Meta-analysis of the included studies. Totally 7 studies with 369 eyes were included. The causes of ME in the final screening study included RVO and DR. Compared with the aflibercept treatment group, the BCVA of the dexamethasone implant treatment group showed no significant difference in the follow-up for 3mo [mean difference (MD): -0.05, 95% confidence interval (CI): -0.11, 0.02; P=0.17] and 12mo (MD: -0.01, 95%CI: -0.38, 0.37; P=0.98), but it was slightly worse than the aflibercept group at 6mo (MD: 0.12, 95%CI: 0.03, 0.21; P=0.008). In terms of CRT reduction, there was no significant difference between the two groups at 3mo (MD: -28.14, 95%CI: -79.95, 23.67; P=0.29), 6mo (MD: 27.67, 95%CI: -84.89, 140.24; P=0.63), and 12mo (MD: -59.00, 95%CI: -127.37, 9.37; P=0.09). However, dexamethasone implant had fewer injections, but more adverse events such as elevated intraocular pressure (IOP) and cataract. Intravitreal injection of aflibercept and dexamethasone implant can both effectively increase BCVA and reduce CRT. Compared with aflibercept, dexamethasone implant is not inferior in improving vision and reducing CRT in the initial treatment period (3mo) and long-term treatment period (12mo). Besides, it has fewer injections and more likely to cause elevated IOP and cataract.

Effect of Intravitreal Aflibercept vs Laser Photocoagulation on Treatment Success of Retinopathy of Prematurity

Laser photocoagulation, which is the standard treatment for retinopathy of prematurity (ROP), can have adverse events. Studies of anti-vascular endothelial growth factor injections have suggested efficacy in the treatment of ROP, but few studies have directly compared them with laser treatments. To compare intravitreal aflibercept vs laser photocoagulation in infants with ROP requiring treatment. This noninferiority, phase 3, 24-week, randomized clinical trial was conducted in 27 countries (64 hospital sites) throughout Asia, Europe, and South America. Overall, 118 infants (gestational age ≤32 weeks at birth or birth weight ≤1500 g) with ROP severity (zone I stage 1+ [stage 1 plus increased disease activity], zone I stage 2+, zone I stage 3, zone I stage 3+, zone II stage 2+, or zone II stage 3+) requiring treatment or with aggressive posterior ROP in at least 1 eye were enrolled between September 25, 2019, and August 28, 2020 (the last visit occurred on February 12, 2021). Infants were randomized 2:1 to receive a 0.4-mg dose of intravitreal aflibercept (n = 75) or laser photocoagulation (n = 43) at baseline. Additional treatment was allowed as prespecified. The primary outcome was the proportion of infants without active ROP and unfavorable structural outcomes 24 weeks after starting treatment (assessed by investigators). The requirement for rescue treatment was considered treatment failure. Intravitreal aflibercept was deemed noninferior if the lower limit of the 1-sided 95% bayesian credible interval for the treatment difference was greater than -5%. Among 118 infants randomized, 113 were treated (mean gestational age, 26.3 [SD, 1.9] weeks; 53 [46.9%] were female; 16.8% had aggressive posterior ROP, 19.5% had zone I ROP, and 63.7% had zone II ROP) and 104 completed the study. Treatment (intravitreal aflibercept: n = 75; laser photocoagulation: n = 38) was mostly bilateral (92.9%), and 82.2% of eyes in the intravitreal aflibercept group received 1 injection per eye. Treatment success was 85.5% with intravitreal aflibercept vs 82.1% with laser photocoagulation (between-group difference, 3.4% [1-sided 95% credible interval, -8.0% to ∞]). Rescue treatment was required in 4.8% (95% CI, 1.9% to 9.6%) of eyes in the intravitreal aflibercept group vs 11.1% (95% CI, 4.9% to 20.7%) of eyes in the laser photocoagulation group. The serious adverse event rates were 13.3% (ocular) and 24.0% (systemic) in the intravitreal aflibercept group compared with 7.9% and 36.8%, respectively, in the laser photocoagulation group. Three deaths, which occurred 4 to 9 weeks after intravitreal aflibercept treatment, were considered unrelated to aflibercept by the investigators. Among infants with ROP, intravitreal aflibercept compared with laser photocoagulation did not meet criteria for noninferiority with respect to the primary outcome of the proportion of infants achieving treatment success at week 24. Further data would be required for more definitive conclusions regarding the comparative effects of intravitreal aflibercept and laser photocoagulation in this population. ClinicalTrials.gov Identifier: NCT04004208.

FOLFIRI plus BEvacizumab or aFLIbercept after FOLFOX‐bevacizumab failure for COlorectal cancer (BEFLICO): An AGEO multicenter study

After failure of first line FOLFOX-bevacizumab for metastatic colorectal cancer (mCRC), adding either bevacizumab or aflibercept to second-line FOLFIRI increases survival compared to FOLFIRI alone. In this French retrospective multicentre cohort, we included patients with a mCRC treated with either FOLFIRI-aflibercept or FOLFIRI-bevacizumab. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS), disease control rate (DCR: CR + PR + SD) and safety. We included 681 patients from 36 centers, 326 and 355 in the aflibercept and bevacizumab groups, respectively. Median age was 64.2 years and 45.2% of patients were men. Most patients had RAS-mutated tumors (80.8%) and synchronous metastases (85.7%). After a median follow up of 31.2months, median OS was 13.0months (95% CI: 11.3-14.7) and 10.4months (95% CI: 8.8-11.4) in the bevacizumab and aflibercept groups, respectively (P < .0001). Median PFS was 6.0months (95% CI: 5.4-6.5) and 5.1months (95% CI: 4.3-5.6) (P < .0001). After adjustment on age, PS, PFS of first line, primary tumor resection, metastasis location and RAS/BRAF status, bevacizumab was still associated with better OS (HR: 0.71, 95% CI: 0.59-0.86, P=.0003). FOLFIRI-bevacizumab combination was associated with longer OS and PFS, and a better tolerability, as compared to FOLFIRI-aflibercept after progression on FOLFOX-bevacizumab.

Safety and Outcomes of Intravitreal Aflibercept in Diabetic Macular Edema - A Systematic Review.

Recent evidence on the role of vascular endothelial growth factor (VEGF) in the pathogenesis of ischemia and microvascular hyperpermeability leading to macular edema has brought anti-VEGF intravitreal therapy into the limelight. We performed a systematic literature review focusing on the outcomes and safety of the intravitreal use of aflibercept in diabetic macular edema. The studies documented cases with at least three consecutive intravitreal injections of aflibercept (IVA) repeated monthly with a follow-up period of at least one year. The outcomes were evaluated in terms of reported functional and anatomical improvement of the macula, as reflected by changes in visual acuity and macular thickness measured by Optical Coherence Tomography (OCT). In addition, for safety assessment, all reported local and general adverse effects were analyzed. All studies showed an overall significant anatomical and functional improvement. In patients with the 5 IVA monthly at the beginning of the therapy, the visual gain at 52 weeks varied widely between 5 and 18.9 EDRS letters, with a mean value of 9.48 letters. The higher gain was obtained in treatment naïve patients, with worse VA and increased CST at baseline. The lower gain was obtained in patients previously treated with anti- VEGF. Anti-Platelet Trialists' Collaboration-defined arterial thromboembolic events were not statistically different between the aflibercept group and the laser group. Intravitreal aflibercept therapy provides significant improvement in visual acuity and a good safety profile. Randomized studies are needed to document the optimal frequency of intravitreal injections for optimal treatment.

EFFECT OF RANIBIZUMAB AND AFLIBERCEPT ON RETINAL PIGMENT EPITHELIAL DETACHEMENT, SUBRETINAL AND INTRARETINAL FLUID IN AGE-RELATED MACULAR DEGENERATION.

The aim of the study was to compare the effect of three initial doses of the anti-VEGF ranibizumab and aflibercept medication on serous pigment epithelial detachment (PED), subretinal fluid (SRF) and intraretinal fluid (IRF) in the macula of treatment naive neovascular AMD (nvAMD) patients. The cohort consists of 148 patients, of which 74 patients were treated with ranibizumab (51 females and 23 males) and 74 with aflibercept (46 females and 28 males). The data was recorded prospectively from the moment of diagnosis and start of treatment for a period of 3 months. At the moment of diagnosis and 3 months later, an OCT examination (Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany) was performed. The OCT examination included a macular scan with 25 scans. Using the OCT instrument software, we measured the maximum anterior-posterior elevation of serous PED, the highest thickness of SRF and the largest diameter of the intraretinal cystic space. The statistical significance of differences between groups was evaluated using the t-test for continuous data and the Fisher exact test for categorical data. Changes in values of continuous variables over time were evaluated using the Wilcoxon paired test. Paired comparisons of binary parameters were determined by the McNemar test. Full regression of PED, SRF and IRF occurred in 3 (4.1%), 25 (39%) and 20 (51%) patients treated with ranibizumab, and in 5 (7.9%, p = 0.470), 28 (47%, p = 0.470) and 25 (57%, p = 0.827) patients treated with aflibercept, respectively. The average regression of PED, SRF and IRF was -60.4 μm (median -37.5 μm), -84.3 μm (median -85 μm) and -109.3 μm (median -81 μm) in patients treated with ranibizumab, and -46.3 μm (median -30 μm, p = 0.389), -127.7 μm (median -104 μm, p = 0.096) and -204.4 μm (median -163 μm, p = 0.005) in patients treated with aflibercept, respectively. We did not show a statistically significant difference in the regression rates of PED, SRF and IRF between the ranibizumab and aflibercept groups. (in patients with IRF after adjustment of the higher baseline IRF volumes in patients treated with aflibercept, p = 0.891). We are convinced that ranibizumab and aflibercept have the same effect on serous PED, SRF and IRF in the macula in patients with treatment naive nvAMD during the initial loading phase.

MERLIN: Phase 3a, Multicenter, Randomized, Double-Masked Trial of Brolucizumab in Participants with Neovascular Age-Related Macular Degeneration and Persistent Retinal Fluid

To assess the 52-week efficacy and safety of brolucizumab 6 mg administered every 4 weeks compared with aflibercept 2 mg dosed every 4 weeks in eyes with neovascular age-related macular degeneration (nAMD) and persistent retinal fluid. Multicenter, randomized, double-masked phase 3a study. Participants with recalcitrant nAMD (persistent residual retinal fluid despite previous frequent anti-vascular endothelial growth factor treatment). Eyes were randomized (2:1) to intravitreal brolucizumab 6 mg or aflibercept 2 mg every 4 weeks up to and including week100. The primary end point was analysis of noninferiority in mean best-corrected visual acuity (BCVA) change from baseline to week 52 (margin, 4 letters). Other key end points included change in central subfield thickness (CST) from baseline to week 52, fluid-free status (no intraretinal fluid and no subretinal fluid), and safety. At week 52, brolucizumab was noninferior to aflibercept in BCVA change from baseline (least squares mean difference, -0.6 Early Treatment Diabetic Retinopathy Study letters; 95% confidence interval [CI], -2.1 to 0.9; P < 0.001). A total of 4.8% and 1.7% of participants reported a 15-letter or more BCVA loss from baseline at week 52 in the brolucizumab and aflibercept groups, respectively. In eyes treated with brolucizumab compared with those treated with aflibercept, the CST was reduced significantly (P < 0.001), and a significantly greater proportion of eyes were fluid free at week 52 (40.4% brolucizumab vs. 19.0% aflibercept; 95% CI, 13.9-29.0; P < 0.001). Incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, were 9.3% (0.8% and 2.0%) for brolucizumab versus 4.5% (0% and 0%) for aflibercept, respectively. Visual acuity outcomes in previously treated participants with nAMD and persistent retinal fluid receiving brolucizumab 6 mg dosed every 4 weeks were noninferior to aflibercept 2 mg dosed every 4 weeks, with superior anatomic outcomes. However, incidences of IOI, including retinal vasculitis and retinal vascular occlusion, also were higher, leading to study termination.

Comparison of risks of arterial thromboembolic events and glaucoma with ranibizumab and aflibercept intravitreous injection: A nationwide population-based cohort study.

To compare intravitreal aflibercept injection with intravitreal ranibizumab injection for the risk of major arterial thromboembolic events (ATEs) and glaucoma. This retrospective, nationwide cohort study investigated 15 611 and 3867 patients aged >50 years with at least one pharmacy claim for intravitreal ranibizumab injection and aflibercept injection between 2011 and 2016, respectively. The inverse probability of treatment weighting method was performed to adjust the baseline difference between the two groups and the hazard risk of adverse events was estimated using the Cox proportional regression model. No significant difference was noted between intravitreal ranibizumab and aflibercept injection for arterial thromboembolic risk, including ischemic stroke and acute myocardial infarction, during a 2-year follow-up (adjusted hazard ratio (HR): 0.87, 95% confidence interval (CI): 0.53-1.42; P = .583). Subgroup analyses revealed that patients age >65 years (adjusted HR: 0.64, 95% CI: 0.45-0.92) and those without coronary artery disease (adjusted HR: 0.59, 95% CI: 0.37-0.95) had significantly lower arterial thromboembolic risk in the aflibercept group than in the ranibizumab group. Additionally, the risk of glaucoma development after intravitreal injection did not significantly differ between the two groups (adjusted HR: 0.63, 95% CI: 0.37-1.06; P = .084). No significant differences in the risk of major ATEs and glaucoma were found between ranibizumab and aflibercept, and aflibercept might be safe for use in elderly patients.

Comparison of Choroidal Thickness, Foveal Avascular Zone, and Macular Capillary Density in Macular Edema Secondary to Branch Retinal Vein Occlusion Treated with Ranibizumab or Aflibercept-A Prospective Study.

This prospective comparative case series aims to compare best-corrected visual acuity (BCVA), retinal microvasculature, and retinal structural changes in patients treated with either ranibizumab or aflibercept for macular edema (ME) secondary to treatment-naïve branch retinal vein occlusion (BRVO) by optical coherence tomography angiography (OCTA). Ten patients were enrolled with macular capillary density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) and foveal avascular zone (FAZ) measured in both eyes before and after treatment. Final central retinal thickness and BCVA improved significantly (p < 0.05), and densities of SCP and DCP of BRVO sectors were significantly lower at baseline than fellow eye counterparts and remained persistently lower during treatment, particularly in the aflibercept group (p < 0.05). SCP density, DCP density of both BRVO sectors (p = 0.0001, p < 0.0001), and non-BRVO sectors (p < 0.0001, p < 0.0001) were significantly correlated with final BCVA for diseased eyes. Using multivariate general linear model analysis, and including OCTA parameters only, but not all of the available clinical data, DCP density of BRVO sectors in both eyes was the most predictive factor for final visual outcome (probability p < 0.0001). OCTA offered further qualitative and quantitative evaluation of treatment-naïve BRVO. Judging by OCTA parameters, not only in the diseased eye but also in the fellow eye, DCP density of BRVO sectors was the most predictive factor of final visual outcome.

Long term results of three anti-vascular endothelial growth factor agents in pachychoroid neovasculopathy

Purpose To assess morphological changes and visual results in eyes with pachychoroid neovasculopathy (PNV) that underwent different intravitreal anti-vascular endothelial growth factor (VEGF) agents. Materials and methods This is a retrospective, observational, comparative study that included 76 PNV eyes in 76 patients that were allocated to three groups according to the monotherapy injection procedure, as follows: the intravitreal bevacizumab (IVB) group, intravitreal ranibizumab (IVR) group, and intravitreal aflibercept (IVA) group. Central macular thickness (CMT), best-corrected visual acuity (BCVA), and subfoveal choroidal thickness (SFCT) were measured at baseline, after treatment 1st month, 3rd month, 6th month, and 12th month, and at the final post-treatment examination. Results Mean age of the patients was 57.31 ± 5.91 years (range: 34–67 years). The mean duration of follow-up was 31.50 ± 12.91 months (range: 13–60 months). The IVB group included 30 eyes, the IVR group included 22 eyes, and the IVA group included 24 eyes. There weren’t any significant differences in BCVA changes between the groups at any post-baseline measurement time point. Although CMT did not change significantly in the IVB group from baseline to the final follow-up visit (baseline: 376.33 ± 86.31 µm; final visit: 340.80 ± 122.70 µm) (p = 0.172), CMT did change significantly in the IVA group (baseline: 383.41 ± 131.83 µm; final visit: 297.33 ± 103.81 µm) (p = 0.029) and IVR group (baseline: 379.18 ± 97.93 µm; final visit: 335.72 ± 111.45 µm) (p = 0.041). SFCT decreased significantly in the IVR and IVA groups (p = 0.015 and p < 0.001, respectively). The mean number of injections was 12.06 ± 4.72 (range: 6–20) in the IVB group, 11.81 ± 3.31(range: 7–17) in the IVR group, and 7.16 ± 3.15 (range: 4–13) in the IVA group (p = 0.004). Conclusion All three anti-VEGFs were effective in terms of visual results in patients with PNV. Patients treated with IVA required fewer injections than those treated with IVB or IVR. Furthermore, IVR and IVA treatment significantly decreased SFCT, whereas IVB did not.

Efficacy of intravitreal injection of aflibercept vs ranibizumab in the treatment of diabetic retinopathy

AIM: To systematically assess the effect of intravitreal injection of Aflibercept or Ranibizumab in the treatment of diabetic retinopathy (DR) by using Meta-analysis. METHODS: PubMed, MEDLINE, Web of Science, Cochrane, Nature Series, ScienceDirect, and ESI Databases were searched until May 2019. Ten studies included a total of 1240 participants with DR had been administered in the Meta-analysis. Aflibercept or ranibizumab via intravitreal injection. After selecting useful information, we used RevMan 5.3 to further analysis. Systematic review and meta-analysis were used to design. RESULTS: The pooled results showed that central macular thickness (CMT) was significantly reduced (P&lt;0.00001) in the intravitreous Aflibercept group (IVA); compared with the intravitreous Ranibizumab group (IVR), which did not greatly improve best corrected visual acuity (BCVA) and visual acuity (VA). CONCLUSION: This Meta-analysis suggests that both IVA and IVR are effective in the treatment of DR patients. Specifically, Aflibercept shows better improvements in CMT, while Ranibizumab is beneficial in increasing BCVA or VA.

Efficacy and toxicity of aflibercept and bevacizumab in combination with FOLFIRI in second‑line therapy for metastatic colon cancer: a retrospective multicenter study

Objective: to compare the efficacy and toxicity of aflibercept and bevacizumab in combination with fOLfIRI in secondline therapy for patients with metastatic colon cancer.Materials and methods. we performed a retrospective analysis of data on patients with metastatic colon cancer treated in 9 clinics in the Russian federation. The inclusion criteria were as follows: metastatic or locally advanced colon cancer; treatment with bevacizumab or aflibercept plus fOLfIRI in the second-line therapy. The primary outcome measure was progression-free survival (PfS). Secondary outcome measures included objective response rate and incidence of adverse events.Results. A total of 271 patients with metastatic colon cancer who received second-line therapy with bevacizumab (n = 81) or aflibercept (n = 190) between 2014 and 2018 were selected for this study. Study groups were matched for main prognostic signs. The objective response rate was 18.1 % in the bevacizumab group and 20.5 % in the aflibercept group (p = 0.7). The median PfS was 5 months (95 % confidence interval 3.8–6.1) in the aflibercept group and 7 months (95 % confidence interval 0.81–2.1) in the bevacizumab group (hazard ratio 1.4; 95 % confidence interval 0.99–2.1; p = 0.04). multivariate regression analysis demonstrated that the type of the targeted drug independently had no effect on PfS (hazard ratio 1.3; 95 % confidence interval 0.9–1.9; p = 0.2). we observed no statistically significant differences in the incidence of complications of any grades between the groups (58 % vs 72 %, p = 0.1). Patients receiving aflibercept were more likely to develop grade III–Iv arterial hypertension (2 % vs 9.5 %) and diarrhea (0 % vs 5.4 %), whereas thrombotic complications were more common in the bevacizumab group (10 % vs 1.8 %).Conclusion. we observed no significant differences in objective response rate and PfS between patients with metastatic colon cancer receiving bevacizumab or aflibercept in combination with fOLfIRI as second-line therapy. The toxicity profiles were different. Our findings can be used for choosing an optimal targeted drug for second-line treatment.

A Comparison of Folinic Acid, Fluorouracil and Irinotecan (FOLFIRI) plus Bevacizumab and FOLFIRI plus Aflibercept as Second-line Treatment for Metastatic Colorectal Cancer

AimTo compare the efficacy and safety of folinic acid, fluorouracil and irinotecan (FOLFIRI) plus bevacizumab or aflibercept in metastatic colorectal cancer (mCRC) patients pretreated with oxaliplatin-based chemotherapy. Materials and methodsWe analysed the treatment outcomes of patients receiving FOLFIRI in combination with bevacizumab or aflibercept as second-line treatment for mCRC between October 2017 and March 2020. This analysis included 67 patients receiving FOLFIRI plus aflibercept and 83 receiving FOLFIRI plus bevacizumab. ResultsThe overall response rate (ORR) was 13.6% (95% confidence interval 4.85–22.34) in the FOLFIRI–aflibercept group and 14.7% (95% confidence interval 6.68–22.71) in the FOLFIRI–bevacizumab group. This difference in ORR was not statistically significant. The median progression-free survival was 8.6 months in the FOLFIRI–bevacizumab group and 8.5 months in the FOLFIRI–aflibercept group (P = 0.752). Patients in the FOLFIRI–bevacizumab group showed a median overall survival of 12.4 months, whereas patients in the FOLFIRI–aflibercept group had a median overall survival of 13.7 months (P = 0.276). There were no significant differences in survival between the two treatment groups. The adverse events were also largely similar between the two groups. However, hypertension of grade 3 or more was more frequent in the FOLFIRI–aflibercept group. ConclusionFOLFIRI plus bevacizumab and FOLFIRI plus aflibercept had similar anti-tumour activities and toxicity profiles when used as second-line therapy in mCRC patients. Based on these data, both aflibercept and bevacizumab are suitable anti-angiogenic agents when used in combination with FOLFIRI for mCRC.

Outcomes after switching eyes that were stable on aflibercept to ranibizumab versus continuing aflibercept in neovascular age-related macular degeneration.

To describe outcomes of neovascular age-related macular degeneration (nAMD) eyes that were stable on aflibercept but switched to ranibizumab compared to eyes maintained on aflibercept over the same period. In this retrospective cohort study, eyes switched from aflibercept to ranibizumab due to intraocular inflammation (IOI) concerns with aflibercept were identified. Data was gathered from 3 visits pre-switch, switch visit (Sw), and 3 visits post-switch (P1, P2, P3). Similar data was gathered on eyes eligible to switch but continued on aflibercept with the middle visit considered the "presumed switch." Outcome measures included visual acuity (VA) and central foveal thickness (CFT). A total of 142 eyes were analyzed with 71 in each of the switch and aflibercept groups. In the switch group, mean CFT increased from 165.7µm at Sw to 184.7µm at P1 (p = 0.009), 180.9µm at P2 (p = 0.007), and 183.3µm at P3 (p = 0.004). VA changed from logMAR 0.43 (20/54) at Sw to 0.49 (20/61) at P1 (p = 0.02), 0.54 (20/69) at P2 (p = 0.008), and 0.53 (20/68) at P3 (p = 0.04). In the aflibercept group, no significant change in CFT was found over the same period. VA changed from logMAR 0.56 (20/72) at the "presumed switch" to 0.58 (20/76) at P1 (p = 0.085), 0.62 (20/83) at P2 (p = 0.001), and 0.59 (20/77) at P3 (p = 0.14). nAMD eyes that were stable or improving on aflibercept but were switched to ranibizumab worsened, while those in a comparable group maintained on aflibercept remained fairly stable, suggesting a potential efficacy difference between the two drugs.

THREE-YEAR TREATMENT OUTCOMES OF AFLIBERCEPT VERSUS RANIBIZUMAB FOR DIABETIC MACULAR EDEMA: Data from the Fight Retinal Blindness! Registry.

Compare the 3-year outcomes of ranibizumab versus aflibercept in eyes with diabetic macular edema in daily practice. This was a retrospective analysis of naive diabetic macular edema eyes starting intravitreal injections of ranibizumab (0.5 mg) or aflibercept (2 mg) from January 1, 2013 to December 31, 2017 that were collected in the Fight Retinal Blindness! Registry. We identified 534 eyes (ranibizumab-267 and aflibercept-267) of 402 patients. The adjusted mean (95% confidence interval) visual acuity change of +1.3 (-0.1 to 4.2) letters in the ranibizumab group and +2.4 (-0.2 to 5.1) letters (P = 0.001) in the aflibercept group at 3 years was not clinically different. However, the adjusted mean CST change seemed to remain significantly different throughout the 3-year period with higher reductions in favor of aflibercept (-87.8 [-108.3 to -67.4] µm for ranibizumab vs. -114.4 [-134.4 to -94.3] for aflibercept; P < 0.01). When baseline visual impairment was moderate (visual acuity ≤68 Early Treatment Diabetic Retinopathy Study letters), we found a faster improvement in visual acuity in eyes treated with aflibercept up until 18 months of treatment than eyes treated with ranibizumab, which then stayed similar until 36 months of treatment, whereas there was no apparent difference when baseline visual impairment was mild (visual acuity ≥69 Early Treatment Diabetic Retinopathy Study letters). The rate of serious adverse events was low. Aflibercept and ranibizumab were both effective and safe for diabetic macular edema over 3 years.

Short-Term Efficacy in Polypoidal Choroidal Vasculopathy Patients Treated With Intravitreal Aflibercept or Conbercept.

PurposeTo compare the short-term efficacy in patients with polypoidal choroidal vasculopathy (PCV) treated using either aflibercept or conbercept.MethodsThis prospective study included 41 patients with treatment-naive PCV (42 eyes). All the patients were treated with either aflibercept or conbercept using an initial series of 3 monthly loading injections. Changes in the best-corrected logMAR visual acuity (BCVA) and anatomic outcomes were evaluated at 3 months.ResultsBCVA was improved with reduction in central choroidal thickness (CCT), central foveal thickness (CFT), and subretinal fluid (SRF) after 3 monthly loading injections in both aflibercept (IVA) and conbercept (IVC) groups. There was no significant difference in either visual or anatomic outcomes between the two groups after 3 months of treatment. However, compared with the IVC group, significantly higher BCVA improvement was observed in the patients in the IVA group with baseline BCVA better than 1. A visual outcome improved ≥3 lines in 13 patients in the IVA group (59%), and 9 patients in the IVC group (45%). A relatively high proportion of polyp regression was observed in the IVA group (63%) compared with the IVC group (55%) via OCTA.ConclusionsVisual and anatomic outcomes were significantly improved in both IVA and IVC groups, but the results suggest a potentially superior short-term response in the IVA group.

Comparison of agents using higher dose anti-VEGF therapy for treatment-resistant neovascular age-related macular degeneration.

To explore the comparative efficacy and safety of higher dose intravitreal bevacizumab, ranibizumab, or aflibercept for treatment-resistant neovascular age-related macular degeneration (nAMD). Retrospective analysis of 37 eyes of 35 patients with treatment-resistant nAMD divided into 3 cohorts based on high-dose treatment received: 3mg aflibercept, 0.75mg or 1.0mg ranibizumab, and 1.8mg or 2.5mg bevacizumab. The eyes were analyzed at standardized time points up to 48months. Included eyes demonstrated active nAMD with persistent exudation on imaging for at least 6months with at least 4 anti-VEGF injections during this time. Outcomes included change in visual acuity (VA), central retinal thickness (CRT), intraocular pressure (IOP), retinal morphology, adverse event occurrence, and yearly intravitreal injection (IVI) rate. There was no significant difference in VA or IOP change compared to the initiation of high-dose treatment for any agent or comparing between agents at any time point (p > 0.05). CRT improved at month 1, 3, 6, and 12 with all 3 agents (p < 0.05 for all) with a greater CRT reduction seen for ranibizumab than aflibercept at month 6 (p < 0.05), although baseline CRT was greater in the ranibizumab group than the aflibercept group (p < 0.05). Mean absolute CRT was similar at month 6 for all agents (p > 0.05). IVI rates pre- and post-conversion to higher-dose therapy were similar (1 injection per 5.7-6.4weeks). Mean follow-up was 22.8months. Higher dose therapy may achieve improved anatomic outcomes and maintain vision, but frequent injections are required to achieve this. There was no detected difference in efficacy or safety between agents.

KESTREL and KITE: 52-Week Results From Two Phase III Pivotal Trials of Brolucizumab for Diabetic Macular Edema

To compare the efficacy and safety of brolucizumab with aflibercept in patients with diabetic macular edema (DME). Double-masked, 100-week, multicenter, active-controlled, randomized trials. Subjects were randomized 1:1:1 to brolucizumab 3 mg/6 mg or aflibercept 2 mg in KESTREL (n=566) or 1:1 to brolucizumab 6 mg or aflibercept 2 mg in KITE (n=360). Brolucizumab groups received 5 loading doses every 6 weeks (q6w) followed by 12-week (q12w) dosing, with optional adjustment to every 8 weeks (q8w) if disease activity was identified at predefined assessment visits; aflibercept groups received 5 doses every 4 weeks (q4w) followed by fixed q8w dosing. The primary endpoint was best-corrected visual acuity (BCVA) change from baseline at Week 52; secondary endpoints included the proportion of subjects maintained on q12w dosing, change in Diabetic Retinopathy Severity Scale score, and anatomical and safety outcomes. At Week 52, brolucizumab 6 mg was noninferior (NI margin 4 letters) to aflibercept in mean change in BCVA from baseline (KESTREL: +9.2 letters vs +10.5 letters; KITE: +10.6 letters vs +9.4 letters; P < .001), more subjects achieved central subfield thickness (CSFT) <280 µm, and fewer had persisting subretinal and/or intraretinal fluid vs aflibercept, with more than half of brolucizumab 6 mg subjects maintained on q12w dosing after loading. In KITE, brolucizumab 6 mg showed superior improvements in change of CSFT from baseline over Week 40 to Week 52 vs aflibercept (P=.001). The incidence of ocular serious adverse events was 3.7% (brolucizumab 3 mg), 1.1% (brolucizumab 6 mg), and 2.1% (aflibercept) in KESTREL; and 2.2% (brolucizumab 6 mg) and 1.7% (aflibercept) in KITE. Brolucizumab 6 mg showed robust visual gains and anatomical improvements with an overall favorable benefit/risk profile in patients with DME.

The effects of subconjunctival bevacizumab, ranibizumab, and aflibercept on corneal neovascularization.

To investigate the effects of subconjunctival bevacizumab, ranibizumab, and aflibercept in an experimental corneal neovascularization model. The eyes of 24 rats were chemically cauterized and randomly divided into four groups: bevacizumab group (0.05mL/1.25mg bevacizumab), ranibizumab group (0.05mL/0.5mg ranibizumab), aflibercept group (0.05mL/1.25mg aflibercept), and control group (0.05mL saline solution). Plasma vascular endothelial growth factor (VEGF) levels were among the major measurement outcomes to assess corneal neovascularization. The collected plasmas were analyzed using the SIGMA RAB0511 Rat VEGF Elisa kit. The PCR technique and VEGF amplification procedures were used for molecular analysis. Each cornea was removed and histologically examined on day 21. Corneal images were evaluated by image analyzer software. In the post-injection period, the number of major corneal arteries decreased significantly in the injection groups when compared to the control group (p = 0.037), but no statistically significant differences were noted among the injection groups (p > 0.05). The aflibercept group had the lowest area of neovascularization. Immunohistochemical staining revealed substantially lower VEGF percentages in neovascularized arteries of the injection groups than the control group (p = 0.015). In TUNEL staining, the mean TUNEL value (number/1hpf) was substantially greater in the control group than in the injection groups, but the mean TUNEL values were similar between the injection groups (p = 0.019, p > 0.05, respectively). No statistically significant differences were observed between the groups in terms of corneal surface area with increased cellularity, edema, and inflammation (p = 0.263). The mean plasma VEGF concentration in the control group was statistically greater than those in the injection groups (p = 0.001). Subconjunctival bevacizumab, ranibizumab, and aflibercept crossed the blood and seemed to be effective in inhibiting corneal neovascularization without causing epitheliopathy in an experimental rat model compared to the controls. However, no significant results were noted between these three anti-VEGF molecules.

Two Year Study of Aflibercept and Ranibizumab Intravitreal Therapy in Patients with Wet AMD.

Background and objectives: The aim of this study was to evaluate the therapeutic results in patients with exudative AMD treated with ranibizumab and aflibercept intravitreal injections over a two-year observation period. Materials and methods: A retrospective observational study was conducted in a clinical hospital on a group of patients who randomly qualified for treatment with Aflibercept (group A) and Ranibizumab (group B) as part of the Polish National Health Fund Medical Program for exudative AMD. Group A consisted of 90 patients, and group B contained 54 patients. The choice of drug in a patient depended solely on the availability of the medication at the time. Before each injection, best corrected visual acuity (BCVA) on the ETDRS scale and central retinal thickness (CRT) were assessed using optical coherence tomography (OCT). Patients from both groups were treated in the first year of treatment with a rigid scheme of 3 doses of 2.0 mg Aflibercept (group A) and 0.5 mg Ranibizumab (group B) at monthly intervals, followed by 4 doses at bimonthly intervals. In the second year, a “pro re nata” scheme was applied. The aim was to evaluate changes in BCVA and CRT after three injections, after 7 injections (about 12 months), and after the second year of therapy (24 months) with reference to the baseline and to compare the effectiveness of the medications. The influences of the following factors were studied: age, gender, initial BCVA, and initial CRT, as well as the number of injections received. Results: No significant statistical differences were found between patients receiving Aflibercept and Ranibizumab therapy in terms of achieving improved visual acuity and reducing retinal thickness after two years of therapy. Conclusions: Both aflibercept and ranibizumab were found to be effective for treating exudative AMD.

Real-life outcomes of intravitreal ranibizumab, aflibercept, and dexamethasone implant administrations in patients with treatment-naïve diabetic macular edema.

PURPOSE:To investigate optical coherence tomography (OCT) biomarker data on visual recovery in treatment-naïve diabetic macular edema (DME) and follow the results of intravitreal ranibizumab (RNB), aflibercept (AFL), and dexamethasone (DEX) implant administration within the 1st year of the pro re nata treatment regimen.METHODS:One hundred and twenty eyes of 102 patients were enrolled in the study. The patients medical records were analyzed retrospectively. Best-corrected visual acuity (BCVA), central macular thickness (CMT), type of DME, presence of subretinal fluid, number and localization of hyperreflective dots, vitreomacular interface disorders, disorganization of the retinal inner layer (DRIL), inner segment/outer segment (IS/OS) junction-external limiting membrane (ELM) status, intraretinal cyst diameter and localization, and subfoveal choroidal thickness were examined in all patients.RESULTS:A statistically significant increase in BCVA and a decrease in CMT were detected in all treatment groups. When cases were evaluated in terms of BCVA before and after treatment, statistically significant differences were observed in the RNB and AFL groups at 1 and 4 months and in the DEX group during the 1st year. In terms of OCT biomarkers, visual recovery was obtained in cases of intact IS/OS-ELM and non-DRIL patients. In the serous macular detachment group, more visual gain was achieved with the RNB (1 and 4 months) and AFL (1, 4, and 6 months) agents compared to the DEX implant. On the other hand, in the group with cystoid macular edema, more visual gain was achieved with RNB compared to the DEX implant in all months, but more visual gain was achieved only in the 1st month with AFL administration.CONCLUSION:Significant improvement was achieved for both BCVA and CMT in all treatment groups. We expect that OCT-based prognostic factors will become more important in the treatment of DME and will be determining factors in the choice of treatment.