Ranibizumab Group Research Articles

Prevalence and Progression of Macular Atrophy in Eyes with Neovascular Age-Related Macular Degeneration in the Phase 2 Ladder Trial of the Port Delivery System with Ranibizumab

To determine whether the rates of macular atrophy (MA) differ between eyes with neovascular age-related macular degeneration (nAMD) treated continuously with the Port Delivery System with ranibizumab (PDS) and those treated with ranibizumab given as a bolus intravitreal injection. A preplanned exploratory analysis of a phase 2, multicenter, randomized, active treatment-controlled, dose-ranging study. Patients diagnosed with nAMD within 9 months of screening who had received at least 2 previous intravitreal anti-vascular endothelial growth factor injections of any agent and were responsive to the treatment. Eyes were randomized (3:3:3:2) to treatment with either the PDS (filled with a customized formulation of ranibizumab at 10, 40, or 100 mg/ml and refilled pro re nata) or monthly intravitreal ranibizumab 0.5-mg injections. The prevalence, incidence, and progression of MA. The analysis population consisted of 220 eyes (58, 62, 59, and 41 eyes in the PDS 10-mg/ml, 40-mg/ml, 100-mg/ml, and monthly intravitreal ranibizumab 0.5-mg injection arms, respectively). At study baseline, MA was observed in 14.5% (PDS 10-mg/ml), 11.5% (PDS 40-mg/ml), 13.6% (PDS 100-mg/ml), and 7.6% (monthly ranibizumab) of eyes. At the last assessment (mean, 22.1 months), the prevalence of MA had increased to 38.6% (PDS 10-mg/ml), 40.0% (PDS 40-mg/ml), 40.4% (PDS 100-mg/ml), and 45.7% (monthly ranibizumab). In patients without MA at baseline, a higher proportion of eyes in the monthly ranibizumab arm (40.6%) developed MA than in those in the PDS arms (28.6%, 32.1%, and 30.6% of eyes in the PDS 10-, 40-, and 100-mg/ml arms, respectively). The mean change in the area of MA from baseline to the last assessment for the PDS 10-mg/ml, 40-mg/ml, 100-mg/ml, and monthly ranibizumab arms was+2.46,+1.61,+1.09, and+1.15 mm2, respectively. At 9 months, for patients without MA at baseline, the difference in the incidence of MA between the PDS 100-mg/ml and monthly ranibizumab groups was-12% (95% confidence interval,-31% to 7%). In the phase 2 Ladder trial, there was no evidence of worse MA with the PDS compared with that with monthly intravitreal ranibizumab 0.5-mg injections. Larger trials focusing on MA are needed to confirm this finding.

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.

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.

Epimacular brachytherapy for previously treated neovascular age-related macular degeneration: month 36 results of the MERLOT randomised controlled trial

Background/aimTo assess the long-term safety and efficacy of epimacular brachytherapy (EMB) for chronic, active, neovascular age-related macular degeneration (nAMD).MethodsThis pivotal, randomised, controlled surgical device trial recruited patients with chronic nAMD...

Efficacy of Intravitreal Injection of Filtered Modified Low-Dose Triamcinolone Acetonide and Ranibizumab on Pseudophakic Cystoid Macular Edema.

PurposeTo compare the visual and morphological effects between intravitreal injection of filtered modified 2 mg triamcinolone acetonide (TA) and 0. 5 mg ranibizumab in patients with pseudophakic cystoid macular edema (PCME).MethodsA retrospective, interventional study was conducted from January 2015 to February 2020 involving patients with PCME after uneventful cataract surgery. A total of 25 patients (25 eyes) with PCME received an intravitreal injection of 0.22 μm filtered modified 2 mg TA, while 15 patients (15 eyes) received 0.5 mg ranibizumab injection. Central macular thickness (CMT), best-corrected visual acuity (BCVA), intraocular pressure (IOP), times of repeated injections, and other side effects were observed at 2 weeks, 1 month, 3 months, and 6 months after injection; then, the data were compared with preinjection information in each group and between the two groups.ResultsBoth the TA and ranibizumab intravitreal injection can achieve improved BCVA and reduced CMT in patients with PCME (P < 0.05), with a trend toward greater improvement in the TA group, but the difference was only significant at 3 months (P < 0.05). IOP was in the normal range without any significant difference (P > 0.05). Thirty-three percent of patients in the ranibizumab group required repeated intravitreal injection compared to 4% in the TA group. Further stratified analysis showed that the better therapeutic effect of the TA group at 3 months after injection only existed in patients with diabetes mellitus (DM), while not in patients without DM. There was no repeat injection in the TA group and 12.5% in the ranibizumab group for patients without DM, while 16.7% in the TA group and 57.1% in the ranibizumab group required repeated injection for patients with DM, which had a significant difference (P < 0.05).ConclusionIntravitreal injection of filtered modified 2 mg TA is safe, effective, and an inexpensive alternative to antivascular endothelial growth factor (anti-VEGF) agents for patients with PCME, especially for patients concurrently with DM. A large number of clinical randomized controlled studies along with long-term follow-up observations are needed.

Prophylactic Ranibizumab to Prevent Neovascular Age-Related Macular Degeneration in Vulnerable Fellow Eyes: A Randomized Clinical Trial

To determine whether prophylactic ranibizumab prevents the development of neovascular age-related macular degeneration (nAMD) in eyes with intermediate age-related macular degeneration (AMD) for patients with preexisting nAMD in their contralateral eye. Multicenter randomized clinical trial. Adults aged 50 years and older with intermediate AMD (multiple intermediate drusen [≥63 μm and <125 μm] or ≥1 large drusen [≥125 μm] and pigmentary changes) in the study eye and nAMD in the contralateral eye. Intravitreal ranibizumab injection (0.5 mg) or sham injection every 3 months for 24 months. Conversion to nAMD over 24 months (primary). Change in best-corrected visual acuity from baseline to 24 months (secondary). Among 108 enrolled participants (54 [50%] in each group), all except 2 were non-Hispanic Whites, 61 participants (56%) were female, and the mean age was 78 years. The mean baseline visual acuity was 77.7 letters (Snellen equivalent 20/32). Conversion to nAMD over 24 months occurred among 7 of 54 eyes (13%) in both groups (ranibizumab vs. sham hazard ratio= 0.91 [95% confidence interval (CI), 0.32-2.59]; P= 0.86). At 24 months, the cumulative incidence of nAMD adjusted for loss to follow-up was 14% (95% CI, 4%-23%) in the ranibizumab group and 15% (95% CI, 4%-25%) in the sham group. At 24 months, the mean change in visual acuity from baseline was-2.1 letters (standard deviation, 5.4 letters) with ranibizumab and-1.4 letters (standard deviation, 7.7 letters) with sham (adjusted difference=-0.8 letters [95% CI, -3.7 to 2.2 letters]; P= 0.62). The proportion of eyes that lost at least 10 letters of visual acuity from baseline at 24 months was 2 of 39 (5%) with ranibizumab and 4 of 40 (10%) with sham. There were no serious ocular adverse events in either group. Quarterly dosing of 0.5 mg ranibizumab in eyes with intermediate AMD did not reduce the incidence of nAMD compared with sham injections; however, the study was likely underpowered given the 95% CI, and a clinically meaningful effect cannot be excluded. There also was no effect on visual acuity at 24 months. Other strategies to reduce neovascular conversion in these vulnerable eyes are needed.

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.

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.

Comparison of Efficacy and Safety between Conbercept and Ranibizumab in Neovascular Age-Related Macular Degeneration: A Meta-Analysis of Randomized Controlled Trials

Background: Conbercept, as a novel vascular endothelial growth factor (VEGF) inhibitor, was approved for the treatment of neovascular age-related macular degeneration (nAMD) in China. Objective: This study aimed to compare the efficacy and safety between conbercept and ranibizumab in patients with nAMD. Methods: Several databases (PubMed, Web of Science, China National Knowledge Infrastructure, and WANFANG) were searched for the results of studies describing conbercept and ranibizumab for the treatment of nAMD. Sixteen randomized controlled trials including 1,224 eyes met our search criteria and were assessed. Results: Conbercept and ranibizumab had comparable effects on improving visual acuity at 3 months (standardized mean difference [SMD]: −0.19; 95% confidence interval [CI]: −0.46 to 0.08; p = 0.17) and 6–12 months (SMD: −0.01; 95% CI: −0.20 to 0.18; p = 0.90). At 3 months and 6–12 months, the differences in the change of central macular thickness in conbercept and ranibizumab groups were 1.06 μm (95% CI: −3.52 to 5.64; p = 0.65) and −0.12 μm (95% CI: −9.26 to 9.02; p = 0.98). In the short term, there was no significant difference between the 2 groups with respect to ocular adverse events (odds ratio [OR]: 0.86; 95% CI: 0.46–1.61; p = 0.63). No significant differences were observed in the recovery rate of choroidal neovascularization leakage between conbercept and ranibizumab at both 3 months (OR: 1.49; 95% CI: 0.83–2.68; p = 0.18) and 6–12 months (OR: 0.66; 95% CI: 0.18–2.43; p = 0.53). There were significant differences between conbercept and ranibizumab in terms of decreasing intraocular pressure (weighted mean difference [WMD]: −1.74; 95% CI: −2.28 to −1.20; p < 0.00001), the plasma VEGF level (WMD: −21.49; 95% CI: −26.28 to −16.70; p < 0.00001), and the C-reactive protein level (WMD: −1.16; 95% CI: −1.45 to −0.87; p < 0.00001) in the short term. Conclusion: Conbercept was similar to ranibizumab in terms of efficacy and safety for the treatment of nAMD in China. Further studies with longer term observation are needed to support this conclusion.

Comparative Risk of Arterial Thromboembolic Events Between Aflibercept and Ranibizumab in Patients with Maculopathy: A Population-Based Retrospective Cohort Study

The increasing numbers of elderly patients and rising incidence of maculopathy raise concerns over arterial thromboembolic events (ATEs) with the use of intravitreal anti-vascular endothelial growth factor (VEGF) medications. This study aimed to compare the risk of ATEs between aflibercept and ranibizumab for maculopathy. We conducted a retrospective population-based cohort study analyzing Taiwan's National Health Insurance Database during 2011-2017 to identify patients with maculopathy receiving intravitreal aflibercept or ranibizumab. The primary outcome was any hospitalization or emergency room visit because of ATEs, including ischemic heart disease (IHD), ischemic stroke (IS), and transient ischemic attack (TIA). The secondary outcome was mortality within 30 days after occurrence of ATE. We employed propensity score methods to generate more homogeneous groups for comparison. We included 5791 aflibercept users and 14,534 ranibizumab users in this study. Compared with the ranibizumab group, the aflibercept group was associated with a lower risk of ATE (hazard ratio [HR] 0.85; 95% confidence interval [CI] 0.80-0.91), with HRs of 0.86 for IHD (95% CI 0.80-0.93), 0.87 for IS (95% CI 0.76-1.00), and 0.57 for TIA (95% CI 0.46-0.71). The risk of 30-day mortality after ATE (HR 1.39; 95% CI 0.80-2.43) and the risk of all-cause mortality (HR 1.02; 95% CI 0.89-1.17) in the aflibercept group was similar to that in the ranibizumab group. The use of aflibercept in patients with maculopathy was associated with a lower risk of ATE than was the use of ranibizumab. There was no difference in mortality risk between the two groups. Our study could provide strong grounds for future prospective studies to confirm the findings.

COMPARISON OF THE EFFECT OF RANIBIZUMAB AND TRIAMCINOLONE ACETONIDE IN DIABETIC MACULAR EDEMA WITH EPIRETINAL MEMBRANE IN PSEUDOPHAKIC PATIENTS

Background: Macular edema is considered the main cause of visual loss in diabetic retinopathy patients. Aim: The aim of this study is to compare the effectivness of Intravitreal Ranibizumab and Triamcinolone acetonide in management of diabetic macular edema with epiretinal membrane in pseudophakic patients. Methods: In this prospective observational study we compared the efficacy of Intravitreal Ranibizumab and Triamcinolone acetonide on 35 eyes of 28 pseudophakic patients with DME with ERM. BCVA , IOP and CMT were recorded to patients before injection and then at 1st , 4th , 8th and 12th week after injection. Results: BCVA improved from 0.5 (0.3–1.4) to reach 0.2 (0–0.9) LogMAR at 12th week postinjection in the Ranibizumab group and improved from 0.6 (0.5–1.6) to 0.4 (0.1–1.5) LogMAR at 12th week postinjection in TA group. IOP changed from baseline of 19.06±2.9 to 23.17±2.68 at 1st week reaching 19.56±1.72 at 12th week (p

Investigation of the Trend of Selecting Anti-Vascular Endothelial Growth Factor Agents for the Initial Treatment of Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy.

BACKGROUND: This study aimed to investigate the trend of selecting ranibizumab and aflibercept for the initial treatment of neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). METHODS: This was a retrospective study that included 460 patients who were diagnosed with treatment-naïve neovascular AMD and PCV and were initially treated with either ranibizumab or aflibercept. The patients were divided into two groups: the ranibizumab group (n = 96) and the aflibercept group (n = 324). The patients’ characteristics and the proportion of the subtypes of macular neovascularization (MNV) were compared between the two groups. RESULTS: Patients in the ranibizumab group were significantly older (mean 74.3 ± 8.4 years) than those in the aflibercept group (mean 70.4 ± 8.8 years; p < 0.001). In the ranibizumab group, the proportions of type 1 or 2 MNV, type 3 MNV, and PCV were 50.0%, 27.1%, and 22.9%, respectively. In the aflibercept group, the proportions were 35.2%, 6.8%, and 58.0%, respectively. There was a significant difference in the proportion of MNV subtypes between the ranibizumab and aflibercept groups (p < 0.001). Ranibizumab was used in 54.2% of patients with type 3 MNVs. However, in patients with PCV, aflibercept was used in 89.5% of patients. CONCLUSIONS: Ranibizumab was preferred as an initial treatment agent in older patients and those with type 3 MNV, whereas aflibercept was highly preferred in patients with PCV. The different characteristics and efficacy of the two agents may have partially contributed to this trend.

Long-term outcomes of ranibizumab vs. aflibercept for neovascular age-related macular degeneration and polypoidal choroidal vasculopathy

To evaluate the long-term outcomes of ranibizumab (RBZ) vs. aflibercept (AFL) in treatment-naïve eyes with typical neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). This multicenter, retrospective, matched-cohort analysis was conducted on data up to 4 years of follow-ups. The primary outcome was the visual acuity (VA) change from baseline. The secondary outcomes included the number of injections, proportion of eyes without a yearly injection, and the number of eyes with treatment switching. Subgroup analyses were performed for typical nAMD and PCV. Typical nAMD was defined as nAMD other than PCV. We included VA-matched 215 eyes of 209 patients (131 and 84 eyes with RBZ and AFL, respectively). The crude mean VA changes from baseline were + 6.7 vs. + 2.6, + 2.1 vs. − 0.4, − 1.3 vs. − 1.8, and − 2.2 vs. − 5.0 letters in the RBZ and AFL groups, at 1, 2, 3, and 4 years, respectively (p > 0.05). The adjusted predicted VA by linear mixed model, proportion of eyes stratified by VA, and the survival curve for significant vision loss were comparable during the 4-year follow-up (p > 0.05). The mean number of injections were similar between the RBZ and AFL groups (2.9 vs. 3.0, respectively, p = 0.692). The subgroup analysis for typical nAMD and PCV showed similar results between the groups. The visual outcomes did not differ between RBZ and AFL during 4 years with comparable numbers of injections. Our study reflects the long-term, real-world clinical practice and treatment pattern of two treatments for typical nAMD and PCV.

A Comparative Study of Ranibizumab and Aflibercept for Neovascular Age-Related Macular Degeneration: 12-Month Outcomes of Polish Therapeutic Program in Non-Tertiary Institution.

IntroductionThis single-center study aimed to compare the 12-month treatment outcomes of ranibizumab with that of aflibercept in routine clinical practice.MethodsCohort of patients diagnosed with treatment-naïve neovascular age-related macular degeneration (AMD), treated using either ranibizumab (n = 33 eyes) or aflibercept (n = 44 eyes) monotherapy over a 12-month follow-up period was analyzed. Anonymous data were extracted from the electronic database dedicated to the drug program.ResultsIn the ranibizumab group, there were no statistically significant changes in best-corrected visual acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] letters) and central retina thickness (CRT) (µm), between baseline (67.9 ± 8.6 & 384.9 ± 97.9) and at 12 months (67.9 ± 12.1 & 398.9 ± 127.1; P = 0.372 & P = 0.884, respectively). In the aflibercept, there was an improvement in BCVA and reduction in CRT between baseline (64.2 ± 8.1 & 414.3 ± 97.8) and at 12 months (70.7 ± 7.4 & 342.3 ± 71.6; P < 0.001 & P < 0.001, respectively). There was no difference in BCVA between the two groups at either diagnosis (P = 0.101) or 12 months (P = 0.917). Mean number of injections in the ranibizumab group was significantly lower (4.9 ± 1.5) than in the aflibercept group (6.7 ± 1; P < 0.001).Conclusions One initial injection of ranibizumab and then pro re nata (PRN) regimen resulted in stabilization of disease progression. Drug selection and treatment scheme could influence twelve-months outcomes. In the aflibercept group, three initial monthly injections and then every two months provided both significant BCVA improvement and CRT reduction at 12 months of treatment.

Observational outcomes in proliferative diabetic retinopathy patients following treatment with ranibizumab, panretinal laser photocoagulation or combination therapy - The non-interventional second year follow-up to the PRIDE study.

Ranibizumab monotherapy showed stronger effects on area of retinal neovascularization (NV) reduction while offering better visual acuity (VA) results than panretinal laser photocoagulation (PRP) monotherapy during the first 12 months of the PRIDE study. The second year of PRIDE was an observational, non-interventional follow-up, performed to evaluate long-term anatomical and functional outcomes in proliferative diabetic retinopathy (PDR) patients under real-life conditions, prior to the approval of ranibizumab for PDR. Seventy-three PDR patients (28 from the ranibizumab group; 20 from the PRP group; 25 from the combination group) were included in the observational follow-up phase and treated at the investigators discretion. Visual acuity (VA) measurements and retinal imaging were performed at Months 12, 18 and 24. Mean (± SD) NV area in the ranibizumab monotherapy and combination follow-up groups increased from 3.16 ± 4.30 mm2 and 1.13 ± 2.78 mm2 at Month 12 to 6.09 ± 10.79 mm2 and 2.14 ± 4.41 mm2 at Month 18 and 10.00 ± 17.63 mm2 and 3.26 ± 7.05 mm2 at Month 24, respectively. In the PRP follow-up group, NV area declined from 5.44 ± 14.55 mm2 at Month 12 to 1.22 ± 1.67 mm2 at Month 18, but increased again to 4.05 ± 11.66 mm2 at Month 24. During the observational phase, only 2 (6;8) patients in the ranibizumab (PRP;combination) follow-up group were treated with anti-VEGF medications, while 17 (6;10) patients received PRP laser therapy. Discontinuation of ranibizumab treatment in PDR patients may result in an increase of NV area and VA loss. Tight monitoring of disease activity and continued treatment beyond the first year is needed to maintain disease control.

Different effects of anti-VEGF drugs (Ranibizumab, Aflibercept, Conbercept) on autophagy and its effect on neovascularization in RF/6A cells

IntroductionChoroidal neovascularization (CNV) is the main pathological change of wet age-related macular degeneration. Anti-VEGF drugs are the most commonly used treatment for CNV. The biggest drawback of anti-VEGF drugs is the recurrence of CNV, which requires repeated therapy several times. Autophagy activation may be involved in reducing the therapeutic effect of anti-VEGF drugs. So, this study aims to elucidate the effect and mechanism of anti-VEGF drugs on endothelial autophagy and neovascularization in vitro. MethodsRF/6A cells were randomly divided into five groups: The control group, hypoxia group (1% O2, 5% CO2, 94% N2), anti-VEGF group (group1: Ranibizumab 100 μg/ml; group2: Aflibercept, 400 μg/ml; group3: Conbercept, 100 μg/ml). Autophagy-related proteins were examined by Western blot. RFP-GFP-LC3 was used to detect autophagy and autophagic flow. Subsequently, we used autophagy inhibitors (3-MA or CQ) to inhibit Conbercept induced autophagy and to observe its effect on angiogenesis in vitro. Proliferation, migration, and tube formation of endothelial cells can be used to study neovascularization in vitro. In this research, the CCK-8 assay was used to detect cell proliferation. Cell migration and tube formation were assessed by wound assay and matrix method, respectively. Flow cytometry and Tunel were used to detect cell apoptosis. Finally, the mechanism of Conbercept activated autophagy was studied. Western blot was used to detect the expression of p53 and DRAM (damage-regulated autophagy modulator), upstream activators of autophagy. ResultsThe protein levels of Beclin-1 and LC3-2/1 in Ranibizumab and Conbercept groups were significantly higher than in the hypoxia group(P < 0.05). While the expression of P62 was decreased (P < 0.05). The autophagic flux was showed the same results. However, Aflibercept showed the opposite effect on autophagy. Compared with the Conbercept group, autophagy inhibitor 3-MA or CQ can further inhibit cell proliferation and promotes cell apoptosis (P < 0.05). Conbercept significantly inhibited cell migration compared with the hypoxia group (633.08 ± 72.52 vs. 546.33 ± 24.61), while the autophagy inhibitor group (3-MA or CQ) had a more obvious inhibition effect (309.75 ± 86.36 and 263.33 ± 68.67) (P < 0.05). For tube formation, the number of tube formation was decreased significantly in the Conbercept group (32.00 ± 2.00) compared to the hypoxia group (39.00 ± 1.53) and even further reduced in 3-MA or CQ group (24.00 ± 3.61, 20.00 ± 2.65). The length of master segments in the hypoxia group was 15,668.00 ± 894.11. It was decreased in Conbercept (13,885.34 ± 730.03). In 3-MA or CQ group, the length of master segments dropped further (11,997.00 ± 433.66, 10,617.67 ± 543.21). Compare with the hypoxia group, the expression P53 and DRAM were increased in the Conbercept group (P < 0.05). Autophagy-related proteins LC-3, Beclin-1, and DRAM were inhibited by P53 inhibitor Pifithrin-α (PFTα) (P < 0.05). ConclusionRanibizumab and Conbercept can trigger the autophagy of vascular endothelial cells while Aflibercept can inhibit it. The combination of Conbercept and autophagy inhibitor can significantly inhibit the formation of angiogenesis in vitro. The mechanism of autophagy activation is related to the activation of the p53/DRAM pathway.

Comparison of conbercept and ranibizumab combined mitomycin C-augmented trabeculectomy for neovascular glaucoma.

To compare the efficacy and security of conbercept and ranibizumab combined with trabeculectomy and panretinal photocoagulation for neovascular glaucoma (NVG). One hundred and sixty patients with NVG were randomly divided into a conbercept group comprised of 80 patients and a ranibizumab group comprised of 80 patients. The postoperative and preoperative visual acuities, intraocular pressures frequency of anti-glaucoma medications, and surgical complications were recorded. The expressions of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (FLT-1), and placenta-like growth factor (PLGF) in the aqueous humor were determined using an enzyme-linked immunosorbent assay. Examining the fundus and obtaining photographs used indirect ophthalmoscopy. Kaplan-Meier and log-rank analyses estimated the success rates. All patient follow-up periods were at 1year. The differences observed in IOP and the frequencies of anti-glaucoma medications at various follow-up time points were not statistically significant (all P > 0.05). The differences observed in both the group visual acuities at various follow-up time points were not statistically significant (P > 0.05). Rates of surgery complications were 18.75% and 25.00% in the conbercept group and ranibizumab group, respectively. The expressions of VEGF, FLT-1, and PLGF significantly decreased (all P < 0.05). The recurrence percentages were 30.00% and 36.25% after conbercept and ranibizumab treatment, respectively. The conbercept effects were similar with that of ranibizumab. Intravitreal injection of conbercept was effective for NVG treatment, which provides a new therapeutic drug for NVG treatment.

Comparison of the effects of intravitreal ranibizumab and aflibercept on retinal vessel diameters in patients with diabetic macular edema

PurposeTo evaluate and compare the effects of intravitreal ranibizumab and aflibercept treatment on retinal vessel diameters in patients with diabetic macular edema (DME). MethodsThirty initial-treatment naïve patients with DME who received three loading doses at monthly intervals of intravitreal ranibizumab or aflibercept were retrospectively reviewed. The diameters of the central retinal artery and vein sections at a distance of 1500 microns from the optical disc boundary were measured and evaluated at baseline and after the first, second, and third month of the treatment, using infrared images from optical coherence tomography (OCT) (Heidelberg Engineering, Heidelberg, Germany). ResultsIn the superotemporal artery (STA) measurements, the mean basal vessel diameter decreased from 110.00 ± 17.25 μm to 102.60 ± 16.90 μm (p = 0.001) in the third month of the treatment in the ranibizumab group. In the aflibercept group, measurements of the basal STA vessel diameter decreased from 110.20 ± 21.25 μm to 103.93 ± 19.03 μm (p = 0.001) at the third month. The mean basal inferotemporal artery (ITA) vessel diameter was significantly decreased at the third month in both ranibizumab (p = 0.001) and aflibercept groups (p = 0.005). In the superotemporal vein (STV) and inferotemporal vein (ITV) measurements, vessel diameters were found significantly decreased at the end of the third month compared with basal measurements in both the ranibizumab (p = 0.001; p = 0.001, respectively) and aflibercept (p = 0.001; p = 0.004, respectively) treatment groups. The retinal vessel measurements were not found to differ significantly between the two intravitreal treatment agents (p > 0.05). ConclusionBoth intravitreal ranibizumab and aflibercept agents cause a significant narrowing in the retinal vessel diameters in patients with DME after three loading doses at monthly intervals.