Ranibizumab Group Research Articles

Real-World Outcomes of Anti-VEGF Treatment for Retinal Vein Occlusion in Portugal.

Retinal vein occlusion (RVO) is an important cause of visual disability in the modern world. We aim to evaluate the real-world outcomes of patients with RVO treated with anti-vascular endothelial growth factor (VEGF) in Portugal. We performed a retrospective, observational, multicenter study including 8 centers across Portugal and 200 patients treated with either ranibizumab or bevacizumab. Data were collected at 3 time points: time of diagnosis (0 time point) and 6 and 12 months after initiating treatment. Demographic and clinical data were collected. Median visual acuity (VA) and central macular thickness (CMT) improved in the branch RVO (BRVO), central RVO (CRVO), bevacizumab, and ranibizumab groups at 6 and 12 months compared to baseline, with CMT improving further only in the CRVO and ranibizumab groups between 6 and 12 months (p = 0.002 and p = 0.001, respectively). The CMT was lower in the ranibizumab group compared to the bevacizumab group both at 6 and 12 months (p<0.02). Median CMT improved in both the good and poor baseline VA groups at 6 and 12 months compared to baseline (p<0.001). Median VA only improved for the group with poor baseline VA at 6 and 12 months of follow-up (p<0.001). Regression analysis identified several baseline variables as predictors of visual outcomes at 6 and 12 months, with different results depending on the analyzed group. Both treatments were effective, although less effective than results reported in clinical trials. The morphologic response was better with ranibizumab compared to bevacizumab, although functionally there were no differences.

Ranibizumab versus aflibercept for macular edema due to central retinal vein occlusion: 18-month results in real-life data.

The objective of this study was to compare the anatomical and functional outcomes of ranibizumab versus aflibercept for the treatment of macular edema due to central retinal vein occlusion (CRVO) in routine clinical practice. Participants in this observational study included 62 treatment-naïve patients with CRVO who received intravitreal injections of either ranibizumab or aflibercept. The demographic data, best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (SD-OCT) characteristics were evaluated at baseline and at months 1, 2, 3, 6, 12 and 18 post-treatment. At month 18, the mean BCVA of ranibizumab-treated eyes increased 7.9 letters, compared to 7.4 letters for eyes receiving aflibercept, with a similar number of injections. There was no statistically significant difference between the two groups in letters or in central subfield thickness at month 18. At the end of the follow-up, 50% of patients in the ranibizumab group and 42.9% in the aflibercept group showed complete resolution of macular edema. Ranibizumab and aflibercept demonstrated similar anatomical and functional outcomes over 18-month follow-up in patients with macular edema due to CRVO, with a similar number of injections.

Short-term effects of intravitreal ranibizumab and bevacizumab administration on 24-h ambulatory blood pressure monitoring recordings in normotensive patients with age-related macular degeneration.

PurposeTo evaluate effects of intravitreal ranibizumab and bevacizumab administration on ambulatory blood pressure monitoring (ABPM) recordings in normotensive patients with age-related macular degeneration (AMD).Patients and methodsA total of 72 patients (mean age: 61.8(6.2) years, 52.8% were females) diagnosed with AMD were included in this study as divided into ranibizumab (n=34) and bevacizumab (n=38) treatment groups. Twenty-four hour, nighttime, and daytime ABMP values for systolic and diastolic BP were recorded in study groups before and after the third intravitreal injection of ranibizumab or bevacizumab.ResultsRanibizumab injection had no impact on ABPM recordings and dipping status. In the bevacizumab group, increased daytime (129.0(6.6) vs 127.7(6.6) mm Hg, P=0.002) and nighttime systolic (116.9(7.5) vs 112.6(7.1) mmHg, p<0.001) BP and decreased daytime diastolic (80.1(6.5) vs 82.4(6.1)mm Hg, P=0.001) BP were noted in the post-injection period. Also, percentage of non-dippers was significantly increased from 5.3% at pre-injection to 28.9% (P=0.004) at the post-injection period.ConclusionIn conclusion, given that it has no significant impact on ABPM recordings and dipping status, in our study, intravitreal ranibizumab injection may be the better choice in the management of AMD.

Intravitreal Ranibizumab in Diabetic Macular Edema: Long-Term Outcomes.

Intravitreal ranibizumab (RBZ) has been shown in multiple randomized clinical trials to be a valuable treatment for diabetic macular edema (DME), promoting a significant improvement in best-corrected visual acuity (BCVA) and in anatomic outcomes. Compared to sham (RISE and RIDE studies), RBZ rapidly and sustainably improved BCVA and decreased macular edema at 2 years, reducing the risk of further vision loss, with low rates of local or systemic side effects. Compared to macular laser photocoagulation (READ-2 study), RBZ provided a greater improvement in BCVA and regression in foveal thickness, but required a higher number of injections compared to patients treated with both RBZ and laser. In RESTORE trial, RBZ alone or combined with macular laser turned out to be superior to laser alone, without significant differences between the 2 RBZ groups. Compared to combined treatment (RBZ or triamcinolone associated with macular laser) or photocoagulation laser alone (Diabetic Retinopathy Clinical Research Network trial), RBZ with prompt or deferred laser was more effective than laser alone at 1-year follow-up. At 3 years, prompt laser was not better than deferring laser for 24 weeks or more. At 5 years, subjects treated with RBZ achieved better long-term visual outcomes than patients managed with triamcinolone or laser followed by very deferred RBZ. In conclusion, randomized clinical trials showed that RBZ was superior to laser in DME treatment, providing excellent long-term visual outcomes. Frequent injections were necessary in most of the patients to properly control DME and maximize the visual benefits.

Switch to Aflibercept in the Treatment of Neovascular AMD: Long-Term Results.

Purpose To report the long-term clinical outcomes after switching from intravitreal bevacizumab or ranibizumab to aflibercept therapy in eyes with AMD. Methods Retrospective analysis of changes in BCVA, SD-OCT image, and frequency of injections after 1, 2, and 3 years of follow-up. Results 164 eyes were analyzed, 101 eyes switched from bevacizumab (group 1) and 63 from ranibizumab (group 2). One year after the switch, there was an overall nonsignificant mean decrease of 2 ETDRS letters in BCVA. Three years after, there was an overall mean decrease of 7 ETDRS letters, which was statistically significant. A significant improvement in the mean CRT was found at 1, 2, and 3 years. There was a significant decrease in the mean number of injections per year (7.8 to 6.5, p < 0.005) between the first and third year. Conclusion Aflibercept can be useful in the management of refractory neovascular AMD, with a good morphological response. However, in the long-term, BCVA stabilization was not achieved.

Correlation of Vascular Endothelial Growth Factor Production with Photochemical Reaction-induced Retinal Edema.

Background:Retinal edema is the major complication of retinal vein occlusion and diabetic retinopathy; it can damage visual function by influencing macular region. This study was to establish a rat retinal edema model and explore the related VEGF expression and observe the responses to anti-VEGF drugs in this model.Methods:A rat retinal edema model was established by inducing photochemical reaction using a 532 nm laser after the intravenous injection of Erythrosin B. Immediately after the laser treatment, models were given intravitreal injections of Ranibizumab or Conbercept to inhibit VEGF expression, and the changes of retinal thickness were measured. Retinal edema was observed using fundus photography (FP), optical coherence tomography (OCT), and fluoresce in fundus angiography (FFA) at 0, 1, 2, 4, 7 and 14 days after intervention. The retinal VEGF expression was measured using enzyme-linked immunosorbent assay (ELISA) and western blotting at each time point. The rat retinal edema model was also used to verify the function of anti-VEGF polypeptide ZY1.Results:Both retinal edema and vascular leakage were clearly observed at 1, 2 and 4 days after photochemical induction and the retinal thickness increased notably over the same period. The retinal VEGF expression peaked at day 1 and retina became thickening simultaneously. After the interventions, the VEGF expression of the Ranibizumab and Conbercept groups decreased at each time point compared to the edema group (26.90 ± 3.57 vs. 40.29 ± 6.68, F = 31.269 on day 1 and 22.36 ± 1.12 vs. 29.92 ± 0.93 F = 163.789 on day 2, both P < 0.01); the mean RT (278 ± 4 vs. 288 ± 3, F = 134.190 on day 1 and 274 ± 7 vs. 284 ± 6, F = 64.367 on day 2, both P < 0.05) and vascular leakage in these groups also decreased. The same results were observed in the ZY1 group, particularly at day 2 (P < 0.05).Conclusions:This retinal edema model induced by a photochemical reaction is reliable and repeatable. Induced edema increases expression of VEGF. This model can be used to test new drugs.

INTRAVITREAL RANIBIZUMAB THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION AND THE RISK OF STROKE: A National Sample Cohort Study.

To evaluate the risk of stroke after ranibizumab treatment for neovascular age-related macular degeneration. National registry data for 1,025,340 random subjects in the year 2002 were used. The ranibizumab group comprised patients diagnosed with neovascular age-related macular degeneration and treated with ranibizumab between 2009 and 2013 (n = 467). The two types of comparison groups were defined as comorbidity-matched controls (n = 2,330) comprised of randomly selected patients (5 per age-related macular degeneration patient), who were matched to the ranibizumab group according to sociodemographic factors, hypertension, atrial fibrillation, and the Charlson comorbidities index, and sociodemographic-matched controls (n = 2,331) matched according to sociodemographic factors only. Each sampled patient was tracked until 2013. The Cox proportional hazard regression was used. Stroke occurred in 6.6% of the ranibizumab group versus 7.0% of the comorbidity-matched controls and 6.7% of the sociodemographic-matched controls; these differences were not statistically significant. The overall incidence of stroke was similar for the ranibizumab group versus the comorbidity-matched controls and sociodemographic-matched controls, based on the multivariable Cox regression (hazard ratio = 0.88; 95% confidence interval, 0.60-1.30; hazard ratio = 0.95, 95% confidence interval, 0.64-1.41, respectively). Ranibizumab treatment for neovascular age-related macular degeneration did not increase the overall risk of stroke, compared with comorbidity-matched controls or sociodemographic-matched controls.

Twenty-four–Month Outcomes of the Ranibizumab for Edema of the Macula in Diabetes – Protocol 3 with High Dose (READ-3) Study

To compare 2.0 mg ranibizumab (RBZ) injections with 0.5 mg RBZ for eyes with center-involved diabetic macular edema (DME). Randomized, controlled, double-masked (to the dose), interventional, multicenter clinical trial. A total of 152 patients (152 eyes) with DME. Eligible eyes were randomized in a 1:1 ratio to 0.5 mg (n= 77) or 2.0 mg (n= 75) RBZ. Study eyes received 6 monthly mandatory injections followed by as-needed injections until month24. The primary efficacy end point of the study was mean change in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) at month 6. Secondary outcomes included the mean change in BCVA and CFT at month 24, and incidence and severity of systemic and ocular adverse events through month24. A total of 152 eyes were randomized in the study. At month 24, the mean improvement from baseline BCVA was+11.06 letters in the 0.5 mg RBZ group (n= 59) and+6.78 letters in the 2.0 mg RBZ group (n= 54) (P= 0.02). The mean numbers of RBZ injections through month 24 were 18.4 and 17.3 in the 0.5 mg and 2.0 mg RBZ groups, respectively (P= 0.08). The mean change in CFT was-192.53 μm in the 0.5 mg RBZ group and-170.64 μm in the 2.0 mg RBZ group (P= 0.41). By month 24, 3 deaths had occurred in the 0.5 mg RBZ group and 3 deaths had occurred in the 2.0 mg RBZ group; 5 of these 6 deaths occurred secondary to cardiovascular causes, and 1 death occurred as the result of severe pneumonia. All 5 patients with a cardiovascular cause of death had a history of coronary heart disease. At month 24, there were significant visual and anatomic improvements in both groups, with subjects in the 0.5 mg RBZ group gaining more vision. Visual and anatomic gains achieved at month 6 were largely maintained through month 24. No new safety events were identified. In this study population, 2.0 mg RBZ does not appear to provide additional benefit over 0.5 mg RBZ.

The Process of Retinal Vascularization after Anti-VEGF Treatment in Retinopathy of Prematurity: A Comparison Study between Ranibizumab and Bevacizumab

Purpose: To compare the effects on the process of retinal vascularization of intravitreal ranibizumab (IVR) and intravitreal bevacizumab (IVB) in the treatment of severe retinopathy of prematurity. Methods: The present study is a bi-centered retrospective study. While 44 eyes of 22 patients in group 1 were applied 0.625 mg bevacizumab, 46 eyes of 23 patients in group 2 were applied 0.25 mg ranibizumab. Retinal vascularization was evaluated clinically. Results: The mean time for completion of vascularization was found to be postmenstrual 55.93 ± 4.13 weeks in group 1 and 56.30 ± 4.30 weeks in group 2. There were significant differences in the recurrence prevalence between the two groups. The prevalence of recurrence was found to be significantly higher in the ranibizumab group than in the bevacizumab group (p = 0.023). Conclusions: The study showed that after IVR or IVB treatment, vascularization could be completed with delay; there were no differences in this delay time between the ranibizumab and bevacizumab groups. Besides, avascular areas may remain in the peripheral retina, and additional treatment may be necessary after IVB or IVR treatment. When the treatment was applied as monotherapy, more recurrence was observed in the ranibizumab group.

Alterations of retinal vessel size after single injection of intravitreal anti‐VEGF for diabetic macular edema

PurposeTo determine the affect of single injection of intravitreal anti‐vascular endothelial growth factor on the retinal vessel caliber in eyes with diabetic macular edema.MethodsOverall 32 patients were enrolled in ranibizumab group, 30 patients were included in bevacizumab group. Each of these groups also was divided into two others consisting of study group and control group. The study groups were composed of injected eyes while the non‐injected fellow eyes served as control group. The patients underwent complete ophthalmic examinations including optical coherence tomography and fundus fluorescein angiography. The primary outcome measures were central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE) and artery‐to‐vein ratio (AVR).ResultsIn ranibizumab study group (n = 32), pre‐injection mean CRAE (175.42 μm) decreased to 169.01 μm at one week and to 167.47 μm at one month (p &lt; 0.001) while baseline CRVE (235.29 μm) decreased initially to 219.90 μm at one week then to 218.36 μm at one month (p &lt; 0.001). In bevacizumab study group (n = 30), pre‐injection CRAE (150.21 μm) decreased to 146.25 μm at one week and to 145.89 μm at one month (p &lt; 0.001) while baseline CRVE (211.87 μm) decreased initially to 204.59 μm at one week then to 205.24 μm at one month (p &lt; 0.001). Pre‐injection AVR values changed significantly (p = 0.001) at one week and at one month in ranibizumab group, but no significant alteration of AVR was observed in bevacizumab group (p = 0.433). In the control groups of both ranibizumab (n = 32) and bevacizumab (n = 30), none of the three parameters altered throughout the study period compared to the baseline (p &gt; 0.05).ConclusionsBoth ranibizumab and bevacizumab injection significantly constricted retinal vessel diameters in eyes with diabetic macular edema.

Comparison between Aflibercept, Ranibizumab intravitreal injection on Neovascular Age‐related macular degeneration patients

PurposeTo investigate the difference of optical coherence tomography (OCT) findings between aflibercept treatment group and ranibizumab treatment group.MethodsThis study include 63 patients (n = 63 eyes) diagnosed with treatment‐naïve neovascular AMD, and they were treated with aflibercept or ranibizumab monthly for 3 months. We compared the changes of the two groups between before the treatment and after the treatment with optical coherence tomography (OCT) findings such as serous pigment epithelium detachment, fibrovascular pigment epithelium detachment, subretinal fluid, intraretinal fluid, dense zone of outer retina, classic neovascularization, and hyper‐reflective dots. And we also compared the changes of BCVA and IS/OS length, ELM length, central foveal thickness with optical OCT between the two groups.ResultsThere were no significant differences between two groups before each treatments. Serous pigment epithelium detachments were disappeared 36% in aflibercept group, 5% in ranibizumab group, and there was significant difference between the two groups (p = 0.021). There was no significant changes such as BCVA change, OCT finding changes except for serous pigment epithelium detachment between the two groups.ConclusionsFor treatment of neovascular AMD patients, aflibercept might be more effective in serous pigment epithelium detachment than ranibizumab. Because there was no significant visual acuity improvement in serous pigment detachment improvement group in both two treatments, it might be necessary to study further about relationship between visual acuity and serous pigment detachment improvement.

Cost-effectiveness of Aflibercept, Bevacizumab, and Ranibizumab for Diabetic Macular Edema Treatment: Analysis From the Diabetic Retinopathy Clinical Research Network Comparative Effectiveness Trial.

Anti-vascular endothelial growth factor (VEGF) medicines have revolutionized diabetic macular edema (DME) treatment. A recent randomized clinical trial comparing anti-VEGF agents for patients with decreased vision from DME found that at 1 year aflibercept (2.0 mg) achieved better visual outcomes than repackaged (compounded) bevacizumab (1.25 mg) or ranibizumab (0.3 mg); the worse the starting vision, the greater the treatment benefit with aflibercept. However, aflibercept and ranibizumab, respectively, are approximately 31 and 20 times more expensive than bevacizumab. To examine the incremental cost-effectiveness ratios (ICERs) of aflibercept, bevacizumab, and ranibizumab for the treatment of DME. Post hoc analysis of efficacy, safety, and resource utilization data at 1-year follow-up from the Diabetic Retinopathy Clinical Research Network Comparative Effectiveness Trial. Patients were enrolled from August 22, 2012, through August 28, 2013, and analysis was performed from August 21, 2014, through November 7, 2015. The ICERs for all trial participants and subgroups with baseline vision of approximate Snellen equivalent 20/32 to 20/40 (better vision) and baseline vision of approximate Snellen equivalent 20/50 or worse (worse vision). One-year trial data were used to calculate cost-effectiveness for 1 year for the 3 anti-VEGF agents; mathematical modeling was then used to project 10-year cost-effectiveness results. The study included 624 participants (mean [SD] age, 60.6 [10.5] years; 45.7% female; 65.5% white), 209 in the aflibercept group, 207 in the bevacizumab group, and 208 in the ranibizumab group. For all participants, during 1 year, the ICERs of aflibercept and ranibizumab compared with bevacizumab were $1 110 000 per quality-adjusted life-year (QALY) and $1 730 000 per QALY, respectively. During 10 years, they were $349 000 per QALY and $603 000 per QALY, respectively. Compared with ranibizumab, aflibercept's ICER was $648 000 per QALY at 1 year and $203 000 per QALY at 10 years. For the subgroup with worse baseline vision, the 10-year ICERs of aflibercept and ranibizumab compared with bevacizumab were $287 000 per QALY and $817 000 per QALY, respectively. In eyes with decreased vision from DME, treatment costs of aflibercept and ranibizumab would need to decrease by 69% and 80%, respectively, to reach a cost-effectiveness threshold of $100 000 per QALY compared with bevacizumab during a 10-year horizon; for the subgroup with worse baseline vision, the costs would need to decrease by 62% and 84%, respectively. Aflibercept (2.0 mg) and ranibizumab (0.3 mg) are not cost-effective relative to bevacizumab for treatment of DME unless their prices decrease substantially. These results highlight the challenges that physicians, patients, and policymakers face when safety and efficacy results are at odds with cost-effectiveness results.

Axial length, refraction, and retinal vascularization 1 year after ranibizumab or bevacizumab treatment for retinopathy of prematurity.

PurposeThe purpose of this study was to report on the axial length, refraction, and retinal vascularization 1 year after ranibizumab or bevacizumab treatment for threshold retinopathy of prematurity.MethodsThe authors conducted a comparative, consecutive, original study.ResultsTwenty-five eyes of 13 patients with threshold retinopathy of prematurity received one intravitreal ranibizumab treatment, and 15 eyes of eight patients received one intravitreal bevacizumab treatment. In the ranibizumab group, the mean gestational age was 26.15±2.08 weeks, with a mean birth weight of 811.15±287.3 g. In the bevacizumab group, the mean gestational age was 26.50±2.14 weeks, with a mean birth weight of 938.38±200.4 g. The mean axial length was 20.34±0.97 mm and the mean spherical equivalent was 0.46±1.36 D in the ranibizumab group, with complete vascularization in 15 of 25 (60%) eyes. The mean axial length was 20.91±1.54 mm and the mean spherical equivalent was −0.60±3.86 D in the bevacizumab group, with complete vascularization in seven of 15 (46.7%) eyes.ConclusionThere were no significant differences in the axial length and refraction between children with threshold retinopathy of prematurity who received intravitreal bevacizumab compared to those who received ranibizumab after 1 year of follow-up. It appeared that the ranibizumab treatment could achieve more complete retinal vascularization than the bevacizumab treatment; however, there was no statistical significance and long-term follow-up is needed.

Ozurdex in age-related macular degeneration as adjunct to ranibizumab (The OARA Study)

ObjectiveTo evaluate the utility of dexamethasone intravitreal implant (DXI; Ozurdex; Allergan, Irvine, Calif.) in combination with ranibizumab (Lucentis; Novartis Pharma AG, Basel, Switzerland) versus ranibizumab monotherapy on visual acuity (VA) and anatomical outcomes in a neovascular age-related macular degeneration (nAMD) cohort. DesignMulticentred, single-blinded, pilot randomized control trial. ParticipantsTen patients 50 years or older with subfoveal choroidal neovascularization secondary to AMD were randomized to receive DXI in combination with ranibizumab (group 1) or ranibizumab alone (group 2) after a 3-month ranibizumab loading period. MethodsGroup 1 patients received 1 DXI after the loading phase with the option of retreatment at months 4 to 6. Ranibizumab was administered pro re nata for 6 months in both study arms. Mean VA and central macular thickness (CMT) reductions from baseline to study endpoint (9 months) were reported in addition to adverse event frequency across study cohorts. ResultsFrom baseline to the study endpoint, VA improved by 10.8 ± 13.2 Early Treatment of Diabetic Retinopathy Study letters in the control arm and 3.0 ± 10.5 letters in the intervention arm (p = 0.331). CMT decreased by 31.7% ± 17.5% and 13.3% ± 27.0% (p = 0.236) for the control and intervention cohorts, respectively. One patient developed intraocular pressure in excess of 30 mm Hg 3 months after DXI administration. ConclusionsFor this nAMD population, no visual or anatomical benefits were observed when treating with DXI in adjunct to ranibizumab relative to ranibizumab monotherapy. DXI-related adverse events were consistent with those previously documented for dexamethasone.

Grid laser with modified pro re nata injection of bevacizumab and ranibizumab in macular edema due to branch retinal vein occlusion: MARVEL report no 2.

PurposeThe purpose of this study was to prospectively study the efficacy of grid laser combined with intravitreal bevacizumab or ranibizumab in eyes with macular edema due to branch retinal vein occlusion.Patients and methodsTreatment-naïve eyes were enrolled to receive injections of ranibizumab or bevacizumab. During the first 6 months, patients were evaluated monthly and injected if the best-corrected visual acuity changed by five or more letters or fluid was noted on spectral domain optical coherence tomography (OCT); during the next 6 months, patients were evaluated bimonthly and injected only if the best-corrected visual acuity decreased by five or more letters with the associated fluid. Grid laser photocoagulation was performed if there was fluid on OCT and was repeated if patients were eligible after a minimum interval of 3 months.ResultsThe mean numbers of ranibizumab and bevacizumab injections were, respectively, 3.2±1.5 and 3.0±1.4 in the first 6 months and 0.3±0.6 and 0.3±0.6 in the last 6 months. Moreover, 55/75 (73.33%) participants did not receive any injections in the last 6 months. The mean reductions in central retinal thickness at 12 months were 165.67 μm (P<0.001; 95% confidence interval −221.50 to −135.0) in the ranibizumab group and 184.78 μm (P<0.001; 95% confidence interval −246.49 to −140.0) in the bevacizumab group (P=0.079). More patients in the bevacizumab group compared to those in the ranibizumab group required rescue laser at 12 months (20 vs eleven; P=0.06).ConclusionBimonthly evaluations after month 6 with very few pro re nata injections were effective in maintaining visual gains achieved during the first 6 months. Grid laser photocoagulation is effective in maintaining the vision even in the presence of fluid on OCT, although it’s required more often in patients treated with bevacizumab.

The Impact of Systemic Factors on Clinical Response to Ranibizumab for Diabetic Macular Edema

To evaluate the effect of systemic factors on best-corrected visual acuity (BCVA) achieved with ranibizumab (Lucentis; Genentech, Inc, South San Francisco, CA) for treatment of diabetic macular edema (DME) in the RIDE and RISE phase 3 studies. Exploratory, post hoc analysis of 2 randomized, double-masked, sham-injection controlled studies. Adults with DME, BCVA of 20/40 to 20/320 Snellen equivalent, and central foveal thickness of 275 μm or more. Analysis of RIDE (clinicaltrials.gov identifier, NCT00473382) and RISE (clinicaltrials.gov identifier, NCT00473330) pooled ranibizumab data through month 24. Change in BCVA was assessed for association with the following covariates: age, body mass index (BMI), blood pressure, serum glucose, glycosylated hemoglobin (HbA1c), blood urea nitrogen, serum creatinine, estimated glomerular filtration rate, and blood chemistry variables. Change in BCVA at month 24 was assessed according to the following categories of diabetes medication use history: insulin only (n= 193), insulin plus other medications (n= 221), or other noninsulin medications (n= 331). Change in BCVA from baseline assessed by randomized treatment group in pooled 0.3- and 0.5-mg monthly ranibizumab groups. In patients with DME, vision improvement with ranibizumab was not influenced by systemic factors such as diabetes medication history, serum glucose, HbA1c, renal function, BMI, and blood pressure. Patients taking insulin with or without other medications at baseline had longer diabetes disease duration (mean, 17.4 and 20.9 years, respectively) compared with those taking other noninsulin medications (mean, 11.9 years). At month 24, among ranibizumab-treated patients, the mean BCVA change from baseline (Early Treatment Diabetic Retinopathy Study letters ± standard deviation) was not different between patients taking only insulin (12.6±11.2 letters), insulin plus other medications (12.2±12.4 letters), or other noninsulin medications (14.0±13.7 letters). Mean BCVA change also was comparable among patients taking thiazolidinediones (12.9±9.7 letters) and those not taking thiazolidinediones (13.2±13.3 letters). There were no associations between systemic factors (baseline values or change from baseline) and mean change of BCVA at month 24. These results suggest that visual response to ranibizumab therapy in DME was not influenced by nonocular factors related to systemic management of diabetes in the RIDE and RISE studies.

Clinical Efficacy and Safety of Ranibizumab Versus Dexamethasone for Central Retinal Vein Occlusion (COMRADE C): A European Label Study

To compare the efficacy and safety of the European labels of ranibizumab 0.5mg vs dexamethasone 0.7mg in patients with macular edema secondary to central retinal vein occlusion (CRVO). Phase IIIb, multicenter, double-masked, randomized clinical trial. Patients were randomized (1:1) to receive either monthly ranibizumab followed by pro re nata (PRN) treatment (n= 124) or 1 sustained-release dexamethasone implant followed by PRN sham injections (n= 119). Main outcomes were mean average change in best-corrected visual acuity (BCVA) from baseline to month 1 through month 6, mean change in BCVA, and adverse events (AEs). Of 243 patients, 185 (76.1%) completed the study. No difference was observed in BCVA between ranibizumab and dexamethasone at months 1 and 2. From month 3 to month 6, there was significant difference in BCVA gains in favor of ranibizumab. At month 6, mean average BCVA gain was significantly higher with ranibizumab than with dexamethasone (12.86 vs 2.96 letters; difference 9.91 letters, 95% confidence interval [6.51-13.30]; P < .0001). Mean injection number of ranibizumab was 4.52. Ocular AEs were reported in more patients in the dexamethasone than in the ranibizumab group (86.6% vs 55.6%). Using the European labels, similar efficacy was observed for ranibizumab and dexamethasone at months 1 and 2. However, ranibizumab maintained its efficacy throughout the study, whereas dexamethasone declined from month 3 onward. The main limitation of the study was that dexamethasone patients received only a single treatment during the 6-month study. In clinical practice, dexamethasone retreatment may be required earlier than 6months. Safety findings were similar to those previously reported.

Morphology and Visual Acuity in Aflibercept and Ranibizumab Therapy for Neovascular Age-Related Macular Degeneration in the VIEW Trials

To compare the efficacy of intravitreal aflibercept and ranibizumab on the exudative activity of neovascular age-related macular degeneration (nAMD) using optical coherence tomography (OCT) and to correlate morphologic findings with visual acuity (VA) outcomes. Post hoc analysis of the prospective VIEW trials. Data of 1815 patients randomized to 0.5 mg ranibizumab every 4 weeks (Q4wks), 2 mg aflibercept Q4wks, or 2 mg aflibercept every 8 weeks (Q8wks). Standardized OCT evaluation was performed by masked reading centers for the presence of intraretinal cystoid fluid (IRC), subretinal fluid (SRF), and pigment epithelial detachment (PED). Rates of feature resolution were compared between drugs and regimen. Associations between morphologic features and VA were analyzed using multivariate modeling. Resolution rates of IRC, SRF, and PED, and associations between morphology and VA. At baseline, the proportions of eyes with IRC, SRF, and PED were balanced between the aflibercept and ranibizumab groups. At week 12, IRC resolved in 50% of eyes with both agents. Subretinal fluid resolved in 70% of pooled aflibercept-treated eyes and in 59% of ranibizumab-treated eyes, and PED resolved in 29% and 24% of pooled aflibercept-treated eyes and ranibizumab-treated eyes, respectively. At week 52, IRC resolved in 57% (aflibercept Q4wks), 50% (aflibercept Q8wks), and 52% (ranibizumab) of patients; SRF resolved in 75% (both aflibercept Q4wks/Q8wks) and 66% (ranibizumab) of patients; and PED resolved in 40% (aflibercept Q4wks), 34% (aflibercept Q8wks), and 28% (ranibizumab) of patients. During fixed dosing (weeks 12-52) all exudative features showed synchronized fluctuations after treatment-free visits in the Q8wks aflibercept regimen. During pro re nata dosing (weeks 52-96), greater proportions of patients showed recurrent fluid in all treatment arms. Presence of IRC was generally associated with lower VA at baseline, which translated into poorer final VA outcomes. Fluid resolution in all compartments was consistently greater for aflibercept Q4wks than for aflibercept Q8wks and ranibizumab. At week 52, Q8wks aflibercept-treated eyes were, on average, as dry as or drier than with ranibizumab despite the extended treatment interval. Independent of agent or regimen, preexisting morphologic features of the retina at baseline markedly influenced VA outcomes.

Aflibercept vs. Ranibizumab – funktionelle und morphologische Ergebnisse bei mit Ranibizumab vorbehandelter, chronisch-rezidivierender neovaskulärer altersabhängiger Makuladegeneration

Background: To assess functional and morphological outcomes in patients with chronic recurrent neovascular age-related macular degeneration (nAMD) previously treated with ranibizumab, who were either switched from ranibizumab to aflibercept or received further ranibizumab injections. Methods: Retrospective analysis of eyes with recurrent nAMD previously treated with ranibizumab. On recurrence of the macular oedema, patients had received either 3 injections of aflibercept (2.0 mg) or ranibizumab (0.5 mg) at 4 week intervals. Patients were examined before the first injection and four weeks after the last injection. The main outcome measures included change in visual acuity (VA) in logMAR, subfoveal central retinal thickness (CRT), subretinal fluid (SRF) and height of pigment epithelial detachment (PED height), as well as the maximum height of macular subretinal fluid (SRF max) and of macular pigment epithelial detachment (PED height max) in spectral-domain optical coherence tomography (OCT). Changes in VA and OCT were compared between the two groups to investigate differences in the therapeutic effects of aflibercept and ranibizumab. Results: 60 eyes of 55 patients were included. The aflibercept group (n = 30) and the ranibizumab group (n = 30) showed no statistically significant differences in mean age (p = 0.813), number of prior injections of ranibizumab (p = 0.127) or time since last injection (p = 0.523). Mean VA logMAR improved in both groups, though only in the ranibizumab group was the difference significant (0.50 ± 0.33 to 0.44 ± 0.29 logMAR; p = 0.013; Table 1). CRT decreased in the aflibercept (p = 0.133) and ranibizumab groups (p = 0.043). PED height was reduced in both groups (aflibercept p = 0.068; ranibizumab p = 0.241). SRF, SRF max and PED height max showed statistically significant decreases in both groups. Comparison of the aflibercept and the ranibizumab groups showed no statistically significant differences between the two groups in change in VA logMAR (p = 0.680), CRT (p = 0.882), SRF (p = 0.871), PED height (p = 0.524), SRF max (p = 0.940) or PED height max (p = 0.762). Conclusions: Aflibercept and ranibizumab were similarly effective in improving visual acuity and morphological parameters of patients with recurrent nAMD after four months. There were no statistically significant differences in the therapeutic effects of the two drugs.

6-weekly bevacizumab versus 4-weekly ranibizumab for neovascular age-related macular degeneration: a 2-year outcome.

To compare visual acuity and central macular thickness (CMT) changes in neovascular age related macular degeneration patients treated with either 6 weekly bevacizumab regimen or 4 weekly ranibizumab on an as required basis. Patients made an informed choice between bevacizumab 1.25 mg or ranibizumab 0.5 mg. The selected treatment was administered in the first 3 visits. Bevacizumab patients were followed-up 6 weekly and ranibizumab 4 weekly. Retreatment criteria was based on the reduction of >5 letters in the best-corrected visual acuity (BCVA), the presence of retinal fluid on optical coherence tomography (OCT) or new retinal haemorrhage. Visual acuity at 2y bevacizumab patients gained 7.0 letters and ranibizumab 9.2 (P=0.31, 95% CI -6.4 to 2.0). At 2y 86% of bevacizumab and 94% ranibizumab patients had not lost 15 letters or more (P=0.13). Mean CMT decreased at 2y bevacizumab by 146 µm, ranibizumab 160 µm (P=0.72). Mean number of injections was at 2y bevacizumzb 11.9, ranibizumab 10.3 (P=0.023). Bevacizumab 6 weekly on an as required basis was not demonstrably non-inferior to ranibizumab 4 weekly pro re nata (prn) in terms of BCVA and change in CMT. In the bevacizumab group, one more injection was required in the second year compared to the ranibizumab group.