The Experts below are selected from a list of 7413 Experts worldwide ranked by ideXlab platform
Neil M Bressler - One of the best experts on this subject based on the ideXlab platform.
-
rationale and application of the protocol s anti vascular endothelial growth factor algorithm for proliferative diabetic retinopathy
Ophthalmology, 2019Co-Authors: Jennifer K Sun, Adam R Glassman, Neil M Bressler, Wesley T Beaulieu, Cynthia R Stockdale, Christina J Flaxel, Jeffrey G Gross, Michel Shami, Lee M JampolAbstract:Purpose To present the rationale, guidelines, and results of Ranibizumab treatment for proliferative diabetic retinopathy (PDR) in Diabetic Retinopathy Clinical Research Network ( DRCR.net ) Protocol S. Design Post hoc analyses from a randomized clinical trial. Participants Three hundred five participants (394 study eyes) having PDR without prior panretinal photocoagulation (PRP). Methods Intravitreous Ranibizumab (0.5 mg) versus PRP for PDR. Ranbizumab-assigned eyes (n = 191) received monthly injections for 6 months unless resolution was achieved after 4 injections. After 6 months, injections could be deferred if neovascularization was stable over 3 consecutive visits (sustained stability). If neovascularization worsened, monthly treatment resumed. Panretinal photocoagulation could be initiated for failure or futility criteria. Main Outcome Measures Neovascularization status through 2 years. Results At 1 month, 19% (35 of 188) of Ranibizumab-assigned eyes showed complete neovascularization resolution and an additional 60% (113) showed improvement. At 6 months, 52% (80 of 153) showed neovascularization resolution, 3% (4) were improved, 37% (56) were stable, and 8% (13) had worsened since the last visit. Among eyes with versus without resolved neovascularization at 6 months, the median (interquartile range) number of injections between 6 months and 2 years was 4 (1–7; n = 73) versus 7 (4–11; n = 67; P Conclusions The DRCR.net treatment algorithm for PDR can provide excellent clinical outcomes through 2 years for patients initiating anti–vascular endothelial growth factor (VEGF) therapy for PDR. When choosing between anti-VEGF and PRP as first-line therapy for PDR, treatment decisions should be guided by consideration of the relative advantages of each therapeutic method and anticipated patient compliance with follow-up and treatment recommendations.
-
effect of adding dexamethasone to continued Ranibizumab treatment in patients with persistent diabetic macular edema a drcr network phase 2 randomized clinical trial
JAMA Ophthalmology, 2018Co-Authors: Raj K Maturi, Adam R Glassman, Lee M Jampol, Neil M Bressler, Michele Melia, Abdhish R Bhavsar, Danni Liu, Roy W Beck, Omar S Punjabi, Hani SalehihadAbstract:Importance Some eyes have persistent diabetic macular edema (DME) following anti–vascular endothelial growth factor (anti-VEGF) therapy for DME. Subsequently adding intravitreous corticosteroids to the treatment regimen might result in better outcomes than continued anti-VEGF therapy alone. Objective To compare continued intravitreous Ranibizumab alone with Ranibizumab plus intravitreous dexamethasone implant in eyes with persistent DME. Design, Setting, and Participants Phase 2 multicenter randomized clinical trial conducted at 40 US sites in 129 eyes from 116 adults with diabetes between February 2014 and December 2016. Eyes had persistent DME, with visual acuity of 20/32 to 20/320 after at least 3 anti-VEGF injections before a run-in phase, which included an additional 3 monthly 0.3-mg Ranibizumab injections. Data analysis was according to intent to treat. Interventions Following the run-in phase, study eyes that had persistent DME and were otherwise eligible were randomly assigned to receive 700 μg of dexamethasone (combination group, 65 eyes) or sham treatment (Ranibizumab group, 64 eyes) in addition to continued 0.3-mg Ranibizumab in both treatment arms as often as every 4 weeks based on a structured re-treatment protocol. Main Outcomes and Measures The primary outcome was change in mean visual acuity letter score at 24 weeks as measured by the electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS). The principal secondary outcome was change in mean central subfield thickness as measured with the use of optical coherence tomography. Results Of the 116 randomized patients, median age was 65 years (interquartile range [IQR], 58-71 years); 50.9% were female and 60.3% were white. Mean (SD) improvement in visual acuity from randomization was 2.7 (9.8) letters in the combination group and 3.0 (7.1) letters in the Ranibizumab group, with the adjusted treatment group difference (combination minus Ranibizumab) of –0.5 letters (95% CI, −3.6 to 2.5; 2-sidedP = .73). Mean (SD) change in central subfield thickness in the combination group was –110 (86) μm compared with –62 (97) μm for the Ranibizumab group (adjusted difference, –52; 95% CI, −82 to −22; 2-sidedP Conclusions and Relevance Although its use is more likely to reduce retinal thickness and increase intraocular pressure, the addition of intravitreous dexamethasone to continued Ranibizumab therapy does not improve visual acuity at 24 weeks more than continued Ranibizumab therapy alone among eyes with persistent DME following anti-VEGF therapy. Trial Registration clinicaltrials.gov Identifier:NCT01945866
-
cost effectiveness of intravitreous Ranibizumab compared with panretinal photocoagulation for proliferative diabetic retinopathy secondary analysis from a diabetic retinopathy clinical research network randomized clinical trial
JAMA Ophthalmology, 2017Co-Authors: David W Hutton, Lee M Jampol, Neil M Bressler, Joshua D Stein, David J Browning, Adam R GlassmanAbstract:Importance The Diabetic Retinopathy Clinical Research Network Protocol S randomized clinical trial results suggest that Ranibizumab is a reasonable treatment alternative to panretinal photocoagulation (PRP) when managing proliferative diabetic retinopathy (PDR), with or without concomitant baseline diabetic macular edema (DME). However, Ranibizumab injections are costly. Thus, it would be useful to examine the relative cost-effectiveness of these 2 treatment modalities. Objective To evaluate incremental cost-effectiveness ratios of 0.5-mg Ranibizumab therapy vs PRP for PDR. Design, Setting, and Participants Preplanned secondary analysis using efficacy, safety, and resource utilization data through 2 years of follow-up at 55 US sites for 213 adults with PDR. Data were collected from February 2012 to January 2015. Interventions Intravitreous 0.5-mg Ranibizumab at baseline and as frequently as every 4 weeks based on a structured retreatment protocol or PRP at baseline for PDR. Eyes in both groups could receive Ranibizumab for concomitant DME. Main Outcomes and Measures Incremental cost-effectiveness ratios of Ranibizumab compared with PRP evaluated within 2 prespecified subgroups for the study eye: with baseline vision-impairing (Snellen equivalent 20/32 or worse) DME and without baseline vision-impairing DME. Results The study included 305 adults with PDR, the mean age was 52 years, 44% were women, and 52% were white. Of the 46 participants with PDR and vision-impairing DME at baseline, 21 were assigned to the Ranibizumab group and 25 to the PRP group (plus Ranibizumab for DME). Among the remaining participants without baseline vision-impairing DME, 80 and 87 were in the Ranibizumab and PRP groups, respectively. For participants with and without baseline vision-impairing DME, the incremental cost-effectiveness ratios of Ranibizumab therapy compared with PRP were $55 568/quality-adjusted life-year and $662 978/quality-adjusted life-year, respectively, over 2 years. Conclusions and Relevance Over 2 years, compared with PRP, 0.5-mg Ranibizumab as given in this trial is within the $50 000/quality-adjusted life-year to $150 000/quality-adjusted life-year range frequently cited as cost-effective in the United States for eyes presenting with PDR and vision-impairing DME, but not for those with PDR without vision-impairing DME. Trial Registration Clinicaltrials.gov Identifier:NCT01489189.
-
aflibercept bevacizumab or Ranibizumab for diabetic macular edema two year results from a comparative effectiveness randomized clinical trial
Ophthalmology, 2016Co-Authors: John A Wells, Adam R Glassman, Allison R Ayala, Lee M Jampol, Neil M Bressler, Susan B Bressler, Alexander J Brucker, Frederick L Ferris, Robert G Hampton, Chirag JhaveriAbstract:Purpose To provide 2-year results comparing anti–vascular endothelial growth factor (VEGF) agents for center-involved diabetic macular edema (DME) using a standardized follow-up and retreatment regimen. Design Randomized clinical trial. Participants Six hundred sixty participants with visual acuity (VA) impairment from DME. Methods Randomization to 2.0-mg aflibercept, 1.25-mg repackaged (compounded) bevacizumab, or 0.3-mg Ranibizumab intravitreous injections performed up to monthly using a protocol-specific follow-up and retreatment regimen. Focal/grid laser photocoagulation was added after 6 months if DME persisted. Visits occurred every 4 weeks during year 1 and were extended up to every 4 months thereafter when VA and macular thickness were stable. Main Outcome Measures Change in VA, adverse events, and retreatment frequency. Results Median numbers of injections were 5, 6, and 6 in year 2 and 15, 16, and 15 over 2 years in the aflibercept, bevacizumab, and Ranibizumab groups, respectively (global P = 0.08). Focal/grid laser photocoagulation was administered in 41%, 64%, and 52%, respectively (aflibercept vs. bevacizumab, P P = 0.04; bevacizumab vs. Ranibizumab, P = 0.01). At 2 years, mean VA improved by 12.8, 10.0, and 12.3 letters, respectively. Treatment group differences varied by baseline VA ( P = 0.02 for interaction). With worse baseline VA (20/50 to 20/320), mean improvement was 18.1, 13.3, and 16.1 letters, respectively (aflibercept vs. bevacizumab, P = 0.02; aflibercept vs. Ranibizumab, P = 0.18; Ranibizumab vs. bevacizumab, P = 0.18). With better baseline VA (20/32 to 20/40), mean improvement was 7.8, 6.8, and 8.6 letters, respectively ( P > 0.10, for pairwise comparisons). Anti-Platelet Trialists' Collaboration (APTC) events occurred in 5% with aflibercept, 8% with bevacizumab, and 12% with Ranibizumab (global P = 0.047; aflibercept vs. bevacizumab, P = 0.34; aflibercept vs. Ranibizumab, P = 0.047; Ranibizumab vs. bevacizumab, P = 0.20; global P = 0.09 adjusted for potential confounders). Conclusions All 3 anti-VEGF groups showed VA improvement from baseline to 2 years with a decreased number of injections in year 2. Visual acuity outcomes were similar for eyes with better baseline VA. Among eyes with worse baseline VA, aflibercept had superior 2-year VA outcomes compared with bevacizumab, but superiority of aflibercept over Ranibizumab, noted at 1 year, was no longer identified. Higher APTC event rates with Ranibizumab over 2 years warrants continued evaluation in future trials.
-
five year outcomes of Ranibizumab with prompt or deferred laser versus laser or triamcinolone plus deferred Ranibizumab for diabetic macular edema
American Journal of Ophthalmology, 2016Co-Authors: Susan B Bressler, Adam R Glassman, Lee M Jampol, Neil M Bressler, Frederick L Ferris, Talat Almukhtar, Joseph M Googe, Shailesh K Gupta, Michele Melia, John A WellsAbstract:Purpose To compare long-term vision and anatomic effects of Ranibizumab with prompt or deferred laser vs laser or triamcinolone + laser with very deferred Ranibizumab in diabetic macular edema (DME). Design Randomized clinical trial. Methods Eight hundred and twenty-eight study eyes (558 [67%] completed the 5-year visit), at 52 sites, with visual acuity 20/32 to 20/320 and DME involving the central macula were randomly assigned to intravitreous Ranibizumab (0.5 mg) with either (1) prompt or (2) deferred laser; (3) sham injection + prompt laser; or (4) intravitreous triamcinolone (4 mg) + prompt laser. The latter 2 groups could initiate Ranibizumab as early as 74 weeks from baseline, for persistent DME with vision impairment. The main outcome measures were visual acuity, optical coherence central subfield thickness, and number of injections through 5 years. Results At 5 years mean (± standard deviation) change in Early Treatment Diabetic Retinopathy Study visual acuity letter scores from baseline in the Ranibizumab + deferred laser (N = 111), Ranibizumab + prompt laser (N = 124), laser/very deferred Ranibizumab (N = 198), and triamcinolone + laser/very deferred Ranibizumab (N = 125) groups were 10 ± 13, 8 ± 13, 5 ± 14, and 7 ± 14, respectively. The difference (95% confidence interval) in mean change between Ranibizumab + deferred laser and laser/very deferred Ranibizumab and triamcinolone + laser/very deferred Ranibizumab was 4.4 (1.2–7.6, P = .001) and 2.8 (−0.9 to 6.5, P = .067), respectively, at 5 years. Conclusions Recognizing limitations of follow-up available at 5 years, eyes receiving initial Ranibizumab therapy for center-involving DME likely have better long-term vision improvements than eyes managed with laser or triamcinolone + laser followed by very deferred Ranibizumab for persistent thickening and vision impairment.
Paul Mitchell - One of the best experts on this subject based on the ideXlab platform.
-
efficacy and safety of Ranibizumab 0 5 mg for the treatment of macular edema resulting from uncommon causes twelve month findings from prometheus
Ophthalmology, 2018Co-Authors: Giovanni Staurenghi, Sebastian Wolf, Timothy Y Y Lai, Paul Mitchell, Andreas Wenzel, Amitabha Bhaumik, Philip G HykinAbstract:Purpose To evaluate the efficacy and safety of Ranibizumab 0.5 mg in adult patients with macular edema (ME) resulting from any cause other than diabetes, retinal vein occlusion, or neovascular age-related macular degeneration. Design A phase 3, 12-month, double-masked, randomized, sham-controlled, multicenter study. Participants One hundred seventy-eight eligible patients aged ≥18 years. Methods Patients were randomized 2:1 to receive either Ranibizumab 0.5 mg (n = 118) or sham (n = 60) at baseline and month 1. From month 2, patients in both arms received open-label individualized Ranibizumab treatment based on disease activity. A preplanned subgroup analysis was conducted on the primary end point on 5 predefined baseline ME etiologies (inflammatory/post-uveitis, pseudophakic or aphakic, central serous chorioretinopathy, idiopathic, and miscellaneous). Main Outcome Measures Changes in best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study letters) from baseline to month 2 (primary end point) and month 12 and safety over 12 months. Results Overall, 156 patients (87.6%) completed the study. The baseline characteristics were well balanced between the treatment arms. Overall, Ranibizumab showed superior efficacy versus sham from baseline to month 2 (least squares mean BCVA, +5.7 letters vs. +2.9 letters; 1-sided P = 0.0111), that is, a treatment effect (TE) of +2.8 letters. The mean BCVA gain from baseline to month 12 was 9.6 letters with Ranibizumab. The TE at month 2 was variable in the 5 predefined etiology subgroups, ranging from >5-letter gain to 0.5-letter loss. The safety findings were consistent with the well-established safety profile of Ranibizumab. Conclusions The primary end point was met and Ranibizumab showed superiority in BCVA gain over sham in treating ME due to uncommon causes, with a TE of +2.8 letters versus sham at month 2. At month 12, the mean BCVA gain was high (9.6 letters) in the Ranibizumab arm; however, the TE was observed to be variable across the different etiology subgroups, reaching a >1-line TE in BCVA in patients with ME resulting from inflammatory conditions/post-uveitis or after cataract surgery. Overall, Ranibizumab was well tolerated with no new safety findings up to month 12.
-
morphology and visual acuity in aflibercept and Ranibizumab therapy for neovascular age related macular degeneration in the view trials
Ophthalmology, 2016Co-Authors: Sebastian M Waldstein, Christian Simader, Giovanni Staurenghi, Victor N Chong, Paul Mitchell, Glenn J Jaffe, Todd A Katz, Ursula SchmidterfurthAbstract:Purpose 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. Design Post hoc analysis of the prospective VIEW trials. Participants 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). Methods 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. Main Outcome Measures Resolution rates of IRC, SRF, and PED, and associations between morphology and VA. Results 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. Conclusions 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.
-
estimated cases of blindness and visual impairment from neovascular age related macular degeneration avoided in australia by Ranibizumab treatment
PLOS ONE, 2014Co-Authors: Paul Mitchell, Alberto Ferreira, Neil M Bressler, Aaron Osborne, Quan V Doan, Chantal M Dolan, Elena Rochtchina, Mark D Danese, Shoshana Colman, Tien Yin WongAbstract:Intravitreal injections of anti-vascular endothelial growth factor agents, such as Ranibizumab, have significantly improved the management of neovascular age-related macular degeneration. This study used patient-level simulation modelling to estimate the number of individuals in Australia who would have been likely to avoid legal blindness or visual impairment due to neovascular age-related macular degeneration over a 2-year period as a result of intravitreal Ranibizumab injections. The modelling approach used existing data for the incidence of neovascular age-related macular degeneration in Australia and outcomes from Ranibizumab trials. Blindness and visual impairment were defined as visual acuity in the better-seeing eye of worse than 6/60 or 6/12, respectively. In 2010, 14 634 individuals in Australia were estimated to develop neovascular age-related macular degeneration who would be eligible for Ranibizumab therapy. Without treatment, 2246 individuals would become legally blind over 2 years. Monthly 0.5 mg intravitreal Ranibizumab would reduce incident blindness by 72% (95% simulation interval, 70–74%). Ranibizumab given as needed would reduce incident blindness by 68% (64–71%). Without treatment, 4846 individuals would become visually impaired over 2 years; this proportion would be reduced by 37% (34–39%) with monthly intravitreal Ranibizumab, and by 28% (23–33%) with Ranibizumab given as needed. These data suggest that intravitreal injections of Ranibizumab, given either monthly or as needed, can substantially lower the number of cases of blindness and visual impairment over 2 years after the diagnosis of neovascular age-related macular degeneration.
-
patient reported visual function outcomes improve after Ranibizumab treatment in patients with vision impairment due to diabetic macular edema randomized clinical trial
JAMA Ophthalmology, 2013Co-Authors: Paul Mitchell, Alberto Ferreira, Neil M Bressler, Keith Tolley, Meghan Gallagher, Jennifer Petrillo, Robert Wood, Francesco BandelloAbstract:Importance Few data are available on relative changes in vision-related function after treatment for diabetic macular edema (DME). Objective To determine the impact of intravitreal Ranibizumab, 0.5 mg, compared with laser on patient-reported visual function. Design Phase 3, randomized, double-masked, 12-month study (RESTORE). Setting Outpatient retina practices in Australia, Canada, and Europe. Participants Patients 18 years or older with type 1 or 2 diabetes mellitus and visual impairment due to DME. Interventions Patients were randomized to Ranibizumab plus sham laser (n = 116), Ranibizumab plus laser (n = 118), or sham injections plus laser (n = 111). Ranibizumab and sham injections were given for 3 consecutive months then as needed; laser or sham laser treatment was given at baseline then as needed. Main Outcomes and Measures National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) scores at 0, 3, and 12 months for patients receiving 1 or more study treatments with 1 or more postbaseline NEI VFQ-25 assessments and last observation carried forward for missing data. Results Mean baseline NEI VFQ-25 composite scores were 72.8, 73.5, and 74.1 in the Ranibizumab, laser, and Ranibizumab plus laser groups, respectively. At 12 months, the mean composite scores (95% CIs) improved by 5.0 (Ranibizumab vs laser, 2.6 to 7.4; P = .01 vs laser) and 5.4 (Ranibizumab plus laser vs laser alone, 3.3 to 7.4; P = .004 vs laser) from baseline in the Ranibizumab and Ranibizumab plus laser groups, respectively, compared with 0.6 (−1.8 to 3.0) for the laser group. Near activities scores improved by 9.0 (Ranibizumab vs laser, 5.0 to 13.0; P = .01) and 9.1 (Ranibizumab plus laser vs laser, 5.6 to 12.6; P = .006) compared with 1.1 (−3.0 to 5.2) for the laser group, whereas distance activities scores improved by 5.3 (Ranibizumab vs laser, 1.8 to 8.9; P = .04) and 5.6 (Ranibizumab plus laser vs laser, 2.3 to 9.0; P = .03) compared with 0.4 (−3.1 to 3.8) for the laser group. Patients with better baseline visual acuity or lower central retinal thickness had greater improvements with Ranibizumab treatment compared with laser in composite and some subscale scores compared with patients with worse visual acuity or higher central retinal thickness. Conclusions and Relevance These data provide vision-related, patient-reported outcome evidence that mirrors visual acuity outcomes and supports benefits from Ranibizumab or Ranibizumab plus laser treatment for patients with DME and characteristics similar to those enrolled in this randomized clinical trial. Trial Registration clinicaltrials.gov Identifier:NCT00687804
-
two year safety and efficacy of Ranibizumab 0 5 mg in diabetic macular edema interim analysis of the restore extension study
Ophthalmology, 2013Co-Authors: Gabriele E Lang, Frank G. Holz, Florian K P Sutter, Ortrud Gerstner, Andras Berta, Bora Eldem, C Simader, Dianne Sharp, Paul MitchellAbstract:Objective To evaluate the 2-year safety and efficacy of Ranibizumab 0.5 mg in diabetic macular edema (DME). Design Twenty-four-month, open-label, multicenter, Phase IIIb extension study. Participants Two hundred forty of 303 patients with visual impairment due to DME who completed the RESTORE core study and entered the extension. Methods All patients were eligible to receive Ranibizumab 0.5 mg pro re nata (PRN) from month 12 (end of core study) to month 36 based on best-corrected visual acuity (BCVA) stability and disease progression retreatment criteria. Patients were also eligible to receive laser PRN according to Early Treatment Diabetic Retinopathy Study guidelines. A preplanned interim analysis was performed at month 24, stratifying by treatment groups as in the RESTORE core study and referred to as prior Ranibizumab, Ranibizumab plus laser, or laser groups in the extension. Main Outcome Measures Incidence of ocular and nonocular adverse events (AEs) and mean change in BCVA. Results Two hundred twenty patients (92%) completed the month 24 visit. Over 2 years, the most frequent ocular serious AE (SAE) and AE were cataract (2.1%) and eye pain (14.6%), respectively. The main nonocular AEs were nasopharyngitis (18.8%) and hypertension (10.4%). There were no cases of endophthalmitis, and the incidences of nonocular SAEs were low. Of the patients entering the extension, 4 deaths were reported in the second year, none of which were related to study drug or procedure. Mean BCVA gain, central retinal thickness (CRT) decrease, and National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) composite score observed at month 12 were maintained at month 24 (prior Ranibizumab: +7.9 letters, –140.6 μm, and 5.6, respectively; prior Ranibizumab plus laser: +6.7 letters, –133.0 μm, and 5.8, respectively), with an average of 3.9 (prior Ranibizumab) and 3.5 Ranibizumab injections (prior Ranibizumab plus laser). In patients treated with laser alone in the core study, the mean BCVA, CRT, and NEI VFQ-25 composite score improved from month 12 to month 24 (+5.4 letters, –126.6 μm, and 4.3, respectively), with an average of 4.1 Ranibizumab injections. Conclusions Ranibizumab 0.5 mg administered according to prespecified visual stability and disease progression criteria was well tolerated, with no new safety concerns identified over 2 years. Overall, an average of 3.8 Ranibizumab injections was sufficient to maintain (prior Ranibizumab) or improve (prior laser) BCVA, CRT, and NEI VFQ-25 outcomes through the second year. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.
Lee M Jampol - One of the best experts on this subject based on the ideXlab platform.
-
rationale and application of the protocol s anti vascular endothelial growth factor algorithm for proliferative diabetic retinopathy
Ophthalmology, 2019Co-Authors: Jennifer K Sun, Adam R Glassman, Neil M Bressler, Wesley T Beaulieu, Cynthia R Stockdale, Christina J Flaxel, Jeffrey G Gross, Michel Shami, Lee M JampolAbstract:Purpose To present the rationale, guidelines, and results of Ranibizumab treatment for proliferative diabetic retinopathy (PDR) in Diabetic Retinopathy Clinical Research Network ( DRCR.net ) Protocol S. Design Post hoc analyses from a randomized clinical trial. Participants Three hundred five participants (394 study eyes) having PDR without prior panretinal photocoagulation (PRP). Methods Intravitreous Ranibizumab (0.5 mg) versus PRP for PDR. Ranbizumab-assigned eyes (n = 191) received monthly injections for 6 months unless resolution was achieved after 4 injections. After 6 months, injections could be deferred if neovascularization was stable over 3 consecutive visits (sustained stability). If neovascularization worsened, monthly treatment resumed. Panretinal photocoagulation could be initiated for failure or futility criteria. Main Outcome Measures Neovascularization status through 2 years. Results At 1 month, 19% (35 of 188) of Ranibizumab-assigned eyes showed complete neovascularization resolution and an additional 60% (113) showed improvement. At 6 months, 52% (80 of 153) showed neovascularization resolution, 3% (4) were improved, 37% (56) were stable, and 8% (13) had worsened since the last visit. Among eyes with versus without resolved neovascularization at 6 months, the median (interquartile range) number of injections between 6 months and 2 years was 4 (1–7; n = 73) versus 7 (4–11; n = 67; P Conclusions The DRCR.net treatment algorithm for PDR can provide excellent clinical outcomes through 2 years for patients initiating anti–vascular endothelial growth factor (VEGF) therapy for PDR. When choosing between anti-VEGF and PRP as first-line therapy for PDR, treatment decisions should be guided by consideration of the relative advantages of each therapeutic method and anticipated patient compliance with follow-up and treatment recommendations.
-
effect of adding dexamethasone to continued Ranibizumab treatment in patients with persistent diabetic macular edema a drcr network phase 2 randomized clinical trial
JAMA Ophthalmology, 2018Co-Authors: Raj K Maturi, Adam R Glassman, Lee M Jampol, Neil M Bressler, Michele Melia, Abdhish R Bhavsar, Danni Liu, Roy W Beck, Omar S Punjabi, Hani SalehihadAbstract:Importance Some eyes have persistent diabetic macular edema (DME) following anti–vascular endothelial growth factor (anti-VEGF) therapy for DME. Subsequently adding intravitreous corticosteroids to the treatment regimen might result in better outcomes than continued anti-VEGF therapy alone. Objective To compare continued intravitreous Ranibizumab alone with Ranibizumab plus intravitreous dexamethasone implant in eyes with persistent DME. Design, Setting, and Participants Phase 2 multicenter randomized clinical trial conducted at 40 US sites in 129 eyes from 116 adults with diabetes between February 2014 and December 2016. Eyes had persistent DME, with visual acuity of 20/32 to 20/320 after at least 3 anti-VEGF injections before a run-in phase, which included an additional 3 monthly 0.3-mg Ranibizumab injections. Data analysis was according to intent to treat. Interventions Following the run-in phase, study eyes that had persistent DME and were otherwise eligible were randomly assigned to receive 700 μg of dexamethasone (combination group, 65 eyes) or sham treatment (Ranibizumab group, 64 eyes) in addition to continued 0.3-mg Ranibizumab in both treatment arms as often as every 4 weeks based on a structured re-treatment protocol. Main Outcomes and Measures The primary outcome was change in mean visual acuity letter score at 24 weeks as measured by the electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS). The principal secondary outcome was change in mean central subfield thickness as measured with the use of optical coherence tomography. Results Of the 116 randomized patients, median age was 65 years (interquartile range [IQR], 58-71 years); 50.9% were female and 60.3% were white. Mean (SD) improvement in visual acuity from randomization was 2.7 (9.8) letters in the combination group and 3.0 (7.1) letters in the Ranibizumab group, with the adjusted treatment group difference (combination minus Ranibizumab) of –0.5 letters (95% CI, −3.6 to 2.5; 2-sidedP = .73). Mean (SD) change in central subfield thickness in the combination group was –110 (86) μm compared with –62 (97) μm for the Ranibizumab group (adjusted difference, –52; 95% CI, −82 to −22; 2-sidedP Conclusions and Relevance Although its use is more likely to reduce retinal thickness and increase intraocular pressure, the addition of intravitreous dexamethasone to continued Ranibizumab therapy does not improve visual acuity at 24 weeks more than continued Ranibizumab therapy alone among eyes with persistent DME following anti-VEGF therapy. Trial Registration clinicaltrials.gov Identifier:NCT01945866
-
cost effectiveness of intravitreous Ranibizumab compared with panretinal photocoagulation for proliferative diabetic retinopathy secondary analysis from a diabetic retinopathy clinical research network randomized clinical trial
JAMA Ophthalmology, 2017Co-Authors: David W Hutton, Lee M Jampol, Neil M Bressler, Joshua D Stein, David J Browning, Adam R GlassmanAbstract:Importance The Diabetic Retinopathy Clinical Research Network Protocol S randomized clinical trial results suggest that Ranibizumab is a reasonable treatment alternative to panretinal photocoagulation (PRP) when managing proliferative diabetic retinopathy (PDR), with or without concomitant baseline diabetic macular edema (DME). However, Ranibizumab injections are costly. Thus, it would be useful to examine the relative cost-effectiveness of these 2 treatment modalities. Objective To evaluate incremental cost-effectiveness ratios of 0.5-mg Ranibizumab therapy vs PRP for PDR. Design, Setting, and Participants Preplanned secondary analysis using efficacy, safety, and resource utilization data through 2 years of follow-up at 55 US sites for 213 adults with PDR. Data were collected from February 2012 to January 2015. Interventions Intravitreous 0.5-mg Ranibizumab at baseline and as frequently as every 4 weeks based on a structured retreatment protocol or PRP at baseline for PDR. Eyes in both groups could receive Ranibizumab for concomitant DME. Main Outcomes and Measures Incremental cost-effectiveness ratios of Ranibizumab compared with PRP evaluated within 2 prespecified subgroups for the study eye: with baseline vision-impairing (Snellen equivalent 20/32 or worse) DME and without baseline vision-impairing DME. Results The study included 305 adults with PDR, the mean age was 52 years, 44% were women, and 52% were white. Of the 46 participants with PDR and vision-impairing DME at baseline, 21 were assigned to the Ranibizumab group and 25 to the PRP group (plus Ranibizumab for DME). Among the remaining participants without baseline vision-impairing DME, 80 and 87 were in the Ranibizumab and PRP groups, respectively. For participants with and without baseline vision-impairing DME, the incremental cost-effectiveness ratios of Ranibizumab therapy compared with PRP were $55 568/quality-adjusted life-year and $662 978/quality-adjusted life-year, respectively, over 2 years. Conclusions and Relevance Over 2 years, compared with PRP, 0.5-mg Ranibizumab as given in this trial is within the $50 000/quality-adjusted life-year to $150 000/quality-adjusted life-year range frequently cited as cost-effective in the United States for eyes presenting with PDR and vision-impairing DME, but not for those with PDR without vision-impairing DME. Trial Registration Clinicaltrials.gov Identifier:NCT01489189.
-
aflibercept bevacizumab or Ranibizumab for diabetic macular edema two year results from a comparative effectiveness randomized clinical trial
Ophthalmology, 2016Co-Authors: John A Wells, Adam R Glassman, Allison R Ayala, Lee M Jampol, Neil M Bressler, Susan B Bressler, Alexander J Brucker, Frederick L Ferris, Robert G Hampton, Chirag JhaveriAbstract:Purpose To provide 2-year results comparing anti–vascular endothelial growth factor (VEGF) agents for center-involved diabetic macular edema (DME) using a standardized follow-up and retreatment regimen. Design Randomized clinical trial. Participants Six hundred sixty participants with visual acuity (VA) impairment from DME. Methods Randomization to 2.0-mg aflibercept, 1.25-mg repackaged (compounded) bevacizumab, or 0.3-mg Ranibizumab intravitreous injections performed up to monthly using a protocol-specific follow-up and retreatment regimen. Focal/grid laser photocoagulation was added after 6 months if DME persisted. Visits occurred every 4 weeks during year 1 and were extended up to every 4 months thereafter when VA and macular thickness were stable. Main Outcome Measures Change in VA, adverse events, and retreatment frequency. Results Median numbers of injections were 5, 6, and 6 in year 2 and 15, 16, and 15 over 2 years in the aflibercept, bevacizumab, and Ranibizumab groups, respectively (global P = 0.08). Focal/grid laser photocoagulation was administered in 41%, 64%, and 52%, respectively (aflibercept vs. bevacizumab, P P = 0.04; bevacizumab vs. Ranibizumab, P = 0.01). At 2 years, mean VA improved by 12.8, 10.0, and 12.3 letters, respectively. Treatment group differences varied by baseline VA ( P = 0.02 for interaction). With worse baseline VA (20/50 to 20/320), mean improvement was 18.1, 13.3, and 16.1 letters, respectively (aflibercept vs. bevacizumab, P = 0.02; aflibercept vs. Ranibizumab, P = 0.18; Ranibizumab vs. bevacizumab, P = 0.18). With better baseline VA (20/32 to 20/40), mean improvement was 7.8, 6.8, and 8.6 letters, respectively ( P > 0.10, for pairwise comparisons). Anti-Platelet Trialists' Collaboration (APTC) events occurred in 5% with aflibercept, 8% with bevacizumab, and 12% with Ranibizumab (global P = 0.047; aflibercept vs. bevacizumab, P = 0.34; aflibercept vs. Ranibizumab, P = 0.047; Ranibizumab vs. bevacizumab, P = 0.20; global P = 0.09 adjusted for potential confounders). Conclusions All 3 anti-VEGF groups showed VA improvement from baseline to 2 years with a decreased number of injections in year 2. Visual acuity outcomes were similar for eyes with better baseline VA. Among eyes with worse baseline VA, aflibercept had superior 2-year VA outcomes compared with bevacizumab, but superiority of aflibercept over Ranibizumab, noted at 1 year, was no longer identified. Higher APTC event rates with Ranibizumab over 2 years warrants continued evaluation in future trials.
-
five year outcomes of Ranibizumab with prompt or deferred laser versus laser or triamcinolone plus deferred Ranibizumab for diabetic macular edema
American Journal of Ophthalmology, 2016Co-Authors: Susan B Bressler, Adam R Glassman, Lee M Jampol, Neil M Bressler, Frederick L Ferris, Talat Almukhtar, Joseph M Googe, Shailesh K Gupta, Michele Melia, John A WellsAbstract:Purpose To compare long-term vision and anatomic effects of Ranibizumab with prompt or deferred laser vs laser or triamcinolone + laser with very deferred Ranibizumab in diabetic macular edema (DME). Design Randomized clinical trial. Methods Eight hundred and twenty-eight study eyes (558 [67%] completed the 5-year visit), at 52 sites, with visual acuity 20/32 to 20/320 and DME involving the central macula were randomly assigned to intravitreous Ranibizumab (0.5 mg) with either (1) prompt or (2) deferred laser; (3) sham injection + prompt laser; or (4) intravitreous triamcinolone (4 mg) + prompt laser. The latter 2 groups could initiate Ranibizumab as early as 74 weeks from baseline, for persistent DME with vision impairment. The main outcome measures were visual acuity, optical coherence central subfield thickness, and number of injections through 5 years. Results At 5 years mean (± standard deviation) change in Early Treatment Diabetic Retinopathy Study visual acuity letter scores from baseline in the Ranibizumab + deferred laser (N = 111), Ranibizumab + prompt laser (N = 124), laser/very deferred Ranibizumab (N = 198), and triamcinolone + laser/very deferred Ranibizumab (N = 125) groups were 10 ± 13, 8 ± 13, 5 ± 14, and 7 ± 14, respectively. The difference (95% confidence interval) in mean change between Ranibizumab + deferred laser and laser/very deferred Ranibizumab and triamcinolone + laser/very deferred Ranibizumab was 4.4 (1.2–7.6, P = .001) and 2.8 (−0.9 to 6.5, P = .067), respectively, at 5 years. Conclusions Recognizing limitations of follow-up available at 5 years, eyes receiving initial Ranibizumab therapy for center-involving DME likely have better long-term vision improvements than eyes managed with laser or triamcinolone + laser followed by very deferred Ranibizumab for persistent thickening and vision impairment.
Lisa Tuomi - One of the best experts on this subject based on the ideXlab platform.
-
Pharmacokinetics of Ranibizumab after Intravitreal Administration in Patients with Retinal Vein Occlusion or Diabetic Macular Edema
Ophthalmology, 2014Co-Authors: Yi Zhang, Nitin Kaila, Peter J. Kuebler, Lisa Tuomi, Jason S. Ehrlich, Roman G. Rubio, Mauricio Maia, Jennifer Visich, Peter A CampochiaroAbstract:Objective To describe the systemic pharmacokinetics of Ranibizumab after intravitreal administration in patients with retinal vein occlusion (RVO) or diabetic macular edema (DME). Design A population approach of nonlinear mixed-effect pharmacokinetics modeling based on serum concentrations of Ranibizumab measured at various times after intravitreal administration. Participants Patients with RVO (n = 441) and DME (n = 435) from 4 large, randomized, phase 3 clinical trials of monthly Ranibizumab intravitreal administration. Methods A 1-compartment pharmacokinetics model with first-order absorption and elimination rate constants previously developed in patients with age-related macular degeneration (AMD) was fitted separately to RVO and DME data. Population pharmacokinetic parameters and interindividual variability were estimated for each model. Baseline covariates were evaluated for potential effects on systemic pharmacokinetics. Model performance was validated using general diagnostic plots and a visual predictive check. Main Outcome Measures Ranibizumab disposition was determined in RVO and DME patients and compared with that previously seen in AMD patients. Results The AMD pharmacokinetics model correctly predicted the measured serum Ranibizumab concentration data for RVO and DME patients. Most observed data points were within the simulated 90% confidence interval, indicating that systemic Ranibizumab concentrations were comparable among AMD, RVO, and DME patients. No disease-related covariates were identified by the population pharmacokinetics analysis. Conclusions The systemic pharmacokinetics of Ranibizumab were similar among patients with AMD, RVO, or DME. Disease-related differences and patient demographics, measured in this study, did not lead to variability in ocular elimination or in systemic exposure of Ranibizumab after intravitreal administration. In all disease processes tested, Ranibizumab exits the eye slowly and then is eliminated rapidly from the circulation, thus minimizing systemic exposure.
-
time to clinically significant visual acuity gains after Ranibizumab treatment for retinal vein occlusion bravo and cruise trials
Ophthalmology, 2014Co-Authors: Allen B Thach, Carol Hoang, Lisa TuomiAbstract:Purpose To assess time to first achievement of clinically significant visual acuity (VA) gains from baseline in patients with retinal vein occlusion (RVO) receiving Ranibizumab versus sham treatment. Design Post hoc analyses of 2 phase 3 clinical trials assessing efficacy and safety of Ranibizumab in patients with branch RVO (Ranibizumab for the Treatment of Macular Edema following Branch Retinal Vein Occlusion: Evaluation of Efficacy and Safety [BRAVO] study; NCT00061594) and central RVO (Ranibizumab for the Treatment of Macular Edema after Central Retinal Vein Occlusion Study: Evaluation of Efficacy and Safety [CRUISE]; NCT00056836) over 12 months. Participants Seven hundred eighty-nine patients (BRAVO, n = 397; CRUISE, n = 392). Intervention Randomization to monthly intraocular Ranibizumab injections (0.3 mg/0.5 mg) or sham. After 6 monthly injections (treatment period), patients meeting prespecified criteria received as-needed (pro re nata [PRN]) Ranibizumab at their assigned dose (sham patients, Ranibizumab 0.5 mg) through month 12 (observation period). BRAVO patients meeting specific eligibility criteria could receive rescue laser treatment once during the treatment and once during the observation periods. Main Outcome Measures Time to first gain of 15 letters or more from baseline, analyzed using Kaplan-Meier methods. To evaluate the effect of delaying Ranibizumab treatment, sham patients' VA data also were analyzed, with month 6 considered as baseline to assess vision gains during the 6 months of receiving Ranibizumab PRN. Results Median time to first 15-letter or more gain from baseline was 12.0 (sham), 4.8 (Ranibizumab 0.3 mg), and 4.0 months (Ranibizumab 0.5 mg) in BRAVO and 12.2, 5.9, and 5.2 months, respectively, in CRUISE. The cumulative proportion of patients who had ever gained 15 letters or more from baseline by month 12 was 50% (sham), 68% (Ranibizumab 0.3 mg), and 71% (Ranibizumab 0.5 mg) in BRAVO and 42%, 61%, and 66%, respectively, in CRUISE. After 6 months of Ranibizumab PRN treatment, a cumulative 10.8% (BRAVO) and 26.2% (CRUISE) of initially sham-treated patients ever gained 15 letters or more. Conclusions This retrospective analysis shows that more than 50% of patients treated with monthly Ranibizumab achieved clinically significant vision gains during the initial 6 months of treatment, which largely were maintained using PRN treatment to 12 months. In comparison, less than 50% of patients initially randomized to sham (and later receiving Ranibizumab 0.5 mg PRN treatment) ever achieved clinically significant vision gains. These results suggest that initiating treatment immediately after diagnosis may provide the greatest vision gains. The potential benefits of early treatment should be evaluated further in prospective clinical studies.
-
pharmacokinetics of Ranibizumab in patients with neovascular age related macular degeneration a population approach
Investigative Ophthalmology & Visual Science, 2013Co-Authors: Lisa Tuomi, Peter J. Kuebler, Nelson L Jumbe, Steve Eppler, Lisa A Damicobeyer, Amita JoshiAbstract:Purpose To characterize Ranibizumab pharmacokinetics in patients with AMD. Methods A population approach of nonlinear mixed-effect pharmacokinetic modeling based on concentration-time data from 2993 serum samples from 674 AMD patients enrolled in 5 phase 1 to 3 clinical trials of single or multiple intravitreal (ITV) doses of Ranibizumab (0.3-2.0 mg/eye) administered biweekly or monthly for up to 24 months. Results A TOTAL OF 696 CONCENTRATION-TIME RECORDS FROM 229 SUBJECTS WITH ONE OR MORE MEASURABLE TOTAL SERUM Ranibizumab CONCENTRATIONS WERE ANALYZED. THE SYSTEMIC CONCENTRATION-TIME DATA FOR Ranibizumab WERE BEST DESCRIBED BY A ONE-COMPARTMENT MODEL WITH FIRST-ORDER ABSORPTION INTO AND FIRST-ORDER ELIMINATION FROM THE SYSTEMIC CIRCULATION. VITREOUS ELIMINATION HALF-LIFE (T1/2) WAS CALCULATED TO BE 9 DAYS AND THE INTRINSIC SYSTEMIC ELIMINATION T1/2 WAS CALCULATED TO BE APPROXIMATELY 2 HOURS. FOLLOWING ITV ADMINISTRATION, Ranibizumab EGRESSES SLOWLY INTO THE SYSTEMIC CIRCULATION, RESULTING IN AN APPARENT SERUM T1/2 OF 9 DAYS. SYSTEMIC-TO-VITREOUS EXPOSURE RATIO WAS ESTIMATED TO BE 1: 90,000. With monthly and quarterly ITV regimens, the serum concentrations of Ranibizumab at steady-state for both the 0.3 and 0.5 mg/eye dose levels were estimated to be below the range needed to inhibit VEGF-A-induced endothelial cell proliferation in vitro by 50% at all times. Conclusions Systemic exposure to Ranibizumab after ITV injection was very low due to elimination on reaching systemic circulation from the vitreous. Population pharmacokinetic analysis of data from a representative sample of AMD patients did not identify clinically significant sources or correlates of variability in Ranibizumab exposure. (ClinicalTrials.gov numbers, NCT00056836, NCT00056823.).
-
horizon an open label extension trial of Ranibizumab for choroidal neovascularization secondary to age related macular degeneration
Ophthalmology, 2012Co-Authors: Michael Singer, Carl C Awh, Srinivas R Sadda, William R Freeman, Andrew N Antoszyk, Pamela Wong, Lisa TuomiAbstract:Objective To evaluate the long-term safety and efficacy of multiple intravitreal Ranibizumab injections (Lucentis, Genentech, Inc., South San Francisco, CA) administered at the investigator's discretion in patients with choroidal neovascularization secondary to age-related macular degeneration. Design An open-label, multicenter, extension study. Participants Patients who completed the controlled treatment phase of 1 of 3 prospective, randomized, 2-year clinical trials of Ranibizumab were eligible for enrollment. Analyses were performed for 3 groups: (1) patients treated with Ranibizumab in the initial study (Ranibizumab treated-initial; n=600); (2) patients randomized to control who crossed over to receive Ranibizumab (Ranibizumab treated-XO; n=190); and (3) Ranibizumab-naive patients (Ranibizumab untreated; n=63). Methods Ranibizumab 0.5 mg was administered at the investigator's discretion. Adverse events (AEs) and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) assessments were conducted at study visits every 3 to 6 months. Main Outcome Measures Incidence and severity of AEs. Results There was 1 occurrence of mild endophthalmitis per 3552 HORIZON injections in the Ranibizumab treated-initial/Ranibizumab treated-XO groups. There were no serious AE reports of lens damage, retinal tears, or rhegmatogenous retinal detachments in the study eyes. The proportion of patients with any single postdose intraocular pressure ≥30 mmHg was 9.2%, 6.6%, and 0%, and the proportion of patients with glaucoma was 3.2%, 4.2%, and 3.2% in the Ranibizumab treated-initial, Ranibizumab treated-XO, and Ranibizumab untreated groups, respectively. Cataract AEs were less frequent in the Ranibizumab untreated group: 6.3% versus 12.5% and 12.1% in the Ranibizumab treated-initial and Ranibizumab treated-XO groups, respectively. The proportion of patients with arterial thromboembolic events as defined by the Antiplatelet Trialists' Collaboration was 5.3% in the Ranibizumab treated-initial and Ranibizumab treated-XO groups, and 3.2% in the Ranibizumab untreated group. At month 48 (2 years of HORIZON), the mean change in BCVA (ETDRS letters) relative to the initial study baseline was 2.0 in the Ranibizumab treated-initial group versus −11.8 in the pooled Ranibizumab treated-XO and Ranibizumab untreated groups. Conclusions Multiple Ranibizumab injections were well tolerated for ≥4 years. With less frequent follow-up leading to less treatment, there was an incremental decline of the visual acuity (VA) gains achieved with monthly treatment. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.
-
incidence of retinal pigment epithelial tears after intravitreal Ranibizumab injection for neovascular age related macular degeneration
Ophthalmology, 2011Co-Authors: Emmett T Cunningham, Lisa Tuomi, Leonard Feiner, Carol Chung, Jason S. EhrlichAbstract:Objective To explore the association between treatment for neovascular age-related macular degeneration (AMD) and incidence and timing of retinal pigment epithelium (RPE) tears in Ranibizumab-treated patients versus control treatment. Design Results from 3 phase III clinical trials ( AN ti-VEGF antibody for the treatment of predominantly classic CHOR oidal neovascularization in age-related macular degeneration [ANCHOR], M inimally classic/occult trial of the A nti-VEGF antibody R anibizumab I n the treatment of N eovascular A ge-related macular degeneration [MARINA], and A P hase IIIb, Multicenter, Randomized, Double-Masked, Sham I njection-Controlled Study of the E fficacy and Safety of R anibizumab in Subjects with Subfoveal Choroidal Neovascularization [CNV] with or without Classic CNV Secondary to Age-Related Macular Degeneration [PIER]) were retrospectively reviewed to identify patients who developed RPE tears during the study period, detected on fluorescein angiography performed at prespecified intervals. Participants Patients with baseline and post-baseline angiographic assessments. Methods Patients received intravitreal Ranibizumab (0.3 or 0.5 mg) or control treatment (verteporfin photodynamic therapy [PDT] in ANCHOR and sham intravitreal injections in ANCHOR, MARINA, and PIER). Main Outcome Measures Incidence and timing of RPE tears during the treatment period. Results Data from 1298 patients were analyzed. No statistically significant differences in RPE tear incidence were observed. The pooled rate of RPE tears was 1.8% with 0.5 mg Ranibizumab, 3.0% with 0.3 mg Ranibizumab, and 1.6% in the control group. Most (76%; 16/21) RPE tears in Ranibizumab-treated patients were identified within 3 months of initiating treatment, whereas the majority (80%; 4/5) of late-onset RPE tears occurred in control patients. In patients who developed RPE tears, better visual acuity (VA) outcomes were observed in those treated with Ranibizumab versus control treatment. Conclusions As studied in these trials, no statistically significant differences in the incidence of RPE tears within a 2-year treatment period were observed in patients who received Ranibizumab (0.5 or 0.3 mg) versus control treatment, although most RPE tears with Ranibizumab occurred within 3 months of initiating treatment. Mean VA was better in patients who developed RPE tears while receiving Ranibizumab than in those who received control treatment, suggesting a potential benefit of continued Ranibizumab therapy in patients with neovascular AMD who developed RPE tears. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.
Peter A Campochiaro - One of the best experts on this subject based on the ideXlab platform.
-
scatter photocoagulation does not reduce macular edema or treatment burden in patients with retinal vein occlusion the relate trial
Ophthalmology, 2015Co-Authors: Peter A Campochiaro, Tahreem A Mir, Gulnar Hafiz, Adrienne W Scott, Ingrid Zimmergaller, Sharon D Solomon, Akrit Sodhi, Elia J Duh, Howard S Ying, Adam S WenickAbstract:Purpose To determine whether scatter and grid laser photocoagulation (laser) adds benefit to Ranibizumab injections in patients with macular edema from retinal vein occlusion (RVO) and to compare 0.5-mg with 2.0-mg Ranibizumab. Design Randomized, double-masked, controlled clinical trial. Participants Thirty-nine patients with central RVO (CRVO) and 42 with branch RVO (BRVO). Methods Subjects were randomized to 0.5 mg or 2.0 mg Ranibizumab every 4 weeks for 24 weeks and re-randomized to pro re nata Ranibizumab plus laser or Ranibizumab alone. Main Outcome Measures Mean change from baseline best-corrected visual acuity (BCVA) at week 24 for BCVA at weeks 48, 96, and 144 for second randomization. Results Mean improvement from baseline BCVA at week 24 was 15.5 and 15.8 letters in the 0.5-mg and 2.0-mg CRVO groups, and 12.1 and 14.6 letters in the 0.5-mg and 2.0-mg BRVO groups. For CRVO, but not BRVO, there was significantly greater reduction from baseline mean central subfield thickness (CST) in the 2.0-mg versus 0.5-mg group (396.1 vs. 253.5 μm; P = 0.03). For the second randomization in CRVO patients, there was no significant difference from week 24 BCVA in the Ranibizumab plus laser versus the Ranibizumab only groups at week 48 (−3.3 vs. 0.0 letters), week 96 (+0.69 vs. −1.6 letters), or week 144 (+0.4 vs. −6.7 letters), and a significant increase from week 24 mean CST at week 48 (+94.7 vs. +15.2 μm; P = 0.05) but not weeks 96 or 144. For BRVO, there was a significant reduction from week 24 mean BCVA in Ranibizumab plus laser versus Ranibizumab at week 48 (−7.5 vs. +2.8; P P Conclusions In patients with macular edema resulting from RVO, there was no short-term clinically significant benefit from monthly injections of 2.0-mg versus 0.5-mg Ranibizumab injections and no long-term benefit in BCVA, resolution of edema, or number of Ranibizumab injections obtained by addition of laser treatment to Ranibizumab.
-
Pharmacokinetics of Ranibizumab after Intravitreal Administration in Patients with Retinal Vein Occlusion or Diabetic Macular Edema
Ophthalmology, 2014Co-Authors: Yi Zhang, Nitin Kaila, Peter J. Kuebler, Lisa Tuomi, Jason S. Ehrlich, Roman G. Rubio, Mauricio Maia, Jennifer Visich, Peter A CampochiaroAbstract:Objective To describe the systemic pharmacokinetics of Ranibizumab after intravitreal administration in patients with retinal vein occlusion (RVO) or diabetic macular edema (DME). Design A population approach of nonlinear mixed-effect pharmacokinetics modeling based on serum concentrations of Ranibizumab measured at various times after intravitreal administration. Participants Patients with RVO (n = 441) and DME (n = 435) from 4 large, randomized, phase 3 clinical trials of monthly Ranibizumab intravitreal administration. Methods A 1-compartment pharmacokinetics model with first-order absorption and elimination rate constants previously developed in patients with age-related macular degeneration (AMD) was fitted separately to RVO and DME data. Population pharmacokinetic parameters and interindividual variability were estimated for each model. Baseline covariates were evaluated for potential effects on systemic pharmacokinetics. Model performance was validated using general diagnostic plots and a visual predictive check. Main Outcome Measures Ranibizumab disposition was determined in RVO and DME patients and compared with that previously seen in AMD patients. Results The AMD pharmacokinetics model correctly predicted the measured serum Ranibizumab concentration data for RVO and DME patients. Most observed data points were within the simulated 90% confidence interval, indicating that systemic Ranibizumab concentrations were comparable among AMD, RVO, and DME patients. No disease-related covariates were identified by the population pharmacokinetics analysis. Conclusions The systemic pharmacokinetics of Ranibizumab were similar among patients with AMD, RVO, or DME. Disease-related differences and patient demographics, measured in this study, did not lead to variability in ocular elimination or in systemic exposure of Ranibizumab after intravitreal administration. In all disease processes tested, Ranibizumab exits the eye slowly and then is eliminated rapidly from the circulation, thus minimizing systemic exposure.
-
predictive value in retinal vein occlusions of early versus late or incomplete Ranibizumab response defined by optical coherence tomography
Ophthalmology, 2013Co-Authors: Robert B Bhisitkul, Peter A Campochiaro, Howard Shapiro, Roman G. RubioAbstract:Purpose To determine if optical coherence tomography (OCT) at baseline or month 3 in the Treatment of Macular Edema following Branch Retinal Vein Occlusion: Evaluation of Efficacy and Safety (BRAVO) and Treatment of Macular Edema following Central Retinal Vein Occlusion: Evaluation of Efficacy and Safety (CRUISE) studies provides information that predicts visual outcome. Design Post hoc analysis from 2 prospective, randomized, controlled clinical trials. Participants Three hundred ninety-seven patients from the BRAVO study and 392 patients from the CRUISE study. Methods Time-domain OCT imaging data were analyzed. Main Outcome Measures Mean change from baseline best-corrected visual acuity (BCVA) letter score at month 6 and month 12. Results Among Ranibizumab-treated patients, 71.2% (0.3 mg) and 78.5% (0.5 mg) in the CRUISE study and 79.1% (0.3 mg) and 84.7% (0.5 mg) in the BRAVO study had central foveal thickness (CFT) of 250 μm or less at month 3 and therefore were categorized as early Ranibizumab responders. Early Ranibizumab responders had excellent visual outcomes regardless of Ranibizumab dose; mean improvement in BCVA letter score at 6 and 12 months was 15.0 to 16.5 (central retinal vein occlusion [CRVO]) and 17.4 to 19.1 (branch retinal vein occlusion [BRVO]). Late or incomplete Ranibizumab responders with CRVO (CFT >250 μm at month 3) did not fare as well as early responders if they were treated with 0.3 mg Ranibizumab (month 6, P = 0.012). At month 6, compared with Ranibizumab-treated CRVO patients with resolved cystoid macular edema (CME) at month 3, those with persistent CME did worse, on average, and significantly so for 0.5 mg (13.1 vs. 18.6; P = 0.027). At baseline, subretinal fluid (SRF) was present in 57% of patients with CRVO and in 45% of patients with BRVO; its presence did not portend a poor outcome in patients treated with Ranibizumab for whom SRF was eliminated in almost all by month 3. Conclusions At month 3 of Ranibizumab treatment, OCT images provide predictive information for patients with CRVO, but not for those with BRVO. Visual outcome at months 6 and 12 was reduced in 0.5 mg Ranibizumab-treated patients with CRVO who had persistent CME at month 3. It also was reduced in CRVO for those with CFT of more than 250 μm at month 3 who were treated with 0.3 mg Ranibizumab. The findings suggest that late or incomplete responders may need careful follow-up. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.
-
Ranibizumab for edema of the macula in diabetes study 3 year outcomes and the need for prolonged frequent treatment
JAMA Ophthalmology, 2013Co-Authors: Quan Dong Nguyen, Gulnar Hafiz, Afsheen Khwaja, Roomasa Channa, Yasir J Sepah, Raafay Sophie, Peter A CampochiaroAbstract:Objective To assess the benefit of increased follow-up and treatment with Ranibizumab between months 24 and 36 in the Ranibizumab for Edema of the Macula in Diabetes (READ-2) Study. Design Prospective, interventional, multicenter follow-up of a randomized clinical trial. Methods Patients who agreed to participate between months 24 and 36 (Ranibizumab, 28 patients; laser, 22; and Ranibizumab + laser, 24) returned monthly and received Ranibizumab, 0.5 mg, if foveal thickness (FTH, center subfield thickness) was 250 μm or greater. Main outcome measures were improvement in best-corrected visual acuity (BCVA) and reduction in FTH between months 24 and 36. Results Mean improvement from the baseline BCVA in the Ranibizumab group was 10.3 letters at month 36 vs 7.2 letters at month 24 (ΔBCVA letters = 3.1, P = .009), and FTH at month 36 was 282 μm vs 352 μm at month 24 (ΔFTH = 70 μm, P = .006). Changes in BCVA and FTH in the laser group (−1.6 letters and −36 μm, respectively) and the Ranibizumab + laser group (+2.0 letters and −24 μm) were not statistically significant. The mean number of Ranibizumab injections was significantly greater in the Ranibizumab group compared with the laser group (5.4 vs 2.3 injections, P = .008) but not compared with the Ranibizumab + laser group (3.3, P = .11). Conclusions More aggressive treatment with Ranibizumab during year 3 resulted in a reduction in mean FTH and improvement in BCVA in the Ranibizumab group. More extensive focal/grid laser therapy in the other 2 groups may have reduced the need for more frequent Ranibizumab injections to control edema. Application to Clinical Practice Long-term visual outcomes for treatment of diabetic macular edema with Ranibizumab are excellent, but many patients require frequent injections to optimally control edema and maximize vision. Trial Registration clinicaltrials.gov Identifier:NCT00407381
-
sustained benefits from Ranibizumab for macular edema following branch retinal vein occlusion 12 month outcomes of a phase iii study
Ophthalmology, 2011Co-Authors: Peter A Campochiaro, Carl C Awh, David M Brown, Young S Lee, Sarah Gray, Namrata Saroj, Wendy Yee Murahashi, Roman G. RubioAbstract:Purpose Assess 12-month efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg Ranibizumab in patients with macular edema after branch retinal vein occlusion (BRVO). Design Prospective, randomized, sham injection-controlled, double-masked, multicenter trial. Participants A total of 397 patients with macular edema after BRVO. Methods Eligible patients were randomized 1:1:1 to 6 monthly injections of 0.3 mg or 0.5 mg Ranibizumab or sham injections. After 6 months, all patients with study eye best-corrected visual acuity (BCVA) ≤20/40 or central subfield thickness ≥250 μm were to receive Ranibizumab. Patients could receive rescue laser treatment once during the treatment period and once during the observation period if criteria were met. Main Outcome Measures The main efficacy outcome reported is mean change from baseline BCVA letter score at month 12. Additional visual and anatomic parameters were assessed. Results Mean (95% confidence interval) change from baseline BCVA letter score at month 12 was 16.4 (14.5–18.4) and 18.3 (15.8–20.9) in the 0.3 mg and 0.5 mg groups, respectively, and 12.1 (9.6–14.6) in the sham/0.5 mg group ( P Conclusions At month 12, treatment with Ranibizumab as needed during months 6–11 maintained, on average, the benefits achieved by 6 monthly Ranibizumab injections in patients with macular edema after BRVO, with low rates of ocular and nonocular safety events. In the sham/0.5 mg group, treatment with Ranibizumab as needed for 6 months resulted in rapid reduction in CFT to a similar level as that in the 0.3 mg Ranibizumab treatment group and an improvement in BCVA, but not to the extent of that in the 2 Ranibizumab groups. Intraocular injections of Ranibizumab provide an effective treatment for macular edema after BRVO. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.
