Efficacy of Every Four Monthly and Quarterly Dosing of Faricimab vs Ranibizumab in Neovascular Age-Related Macular Degeneration: The STAIRWAY Phase 2 Randomized Clinical Trial.

Importance: Faricimab neutralizes angiopoietin-2 and vascular endothelial growth factor A via both simultaneous and independent binding.

Objective: To evaluate extended dosing with faricimab, the first bispecific antibody designed for intraocular use, in patients with neovascular age-related macular degeneration.

Design, Setting, And Participants: This phase 2 randomized clinical trial was a 52-week multicenter, active comparator-controlled, parallel-group study.

Diabetic Population-Based Model to Estimate Impact of Ranibizumab on Diabetic Retinopathy Severity in Patients with Diabetic Macular Edema.

Purpose: Estimate effects of ranibizumab on diabetic retinopathy (DR) severity in US Hispanic and non-Hispanic white persons with center-involved diabetic macular edema (DME) causing vision impairment for whom ranibizumab treatment would be considered.

Patients And Methods: This model simulated DR severity outcomes over 2 years in the better-seeing eye using US census, National Health and Nutrition Examination Survey, Wisconsin Epidemiologic Study of Diabetic Retinopathy, and Los Angeles Latino Eye Study data. Baseline DR severity estimated from Diabetic Retinopathy Clinical Research Network trial data.

The Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration: Results from the Randomized Phase 2 Ladder Clinical Trial.

Purpose: To evaluate the safety and efficacy of the Port Delivery System with ranibizumab (PDS) for neovascular age-related macular degeneration (nAMD) treatment.

Design: Phase 2, multicenter, randomized, active treatment-controlled clinical trial.

Participants: Patients diagnosed with nAMD within 9 months who had received 2 or more prior anti-vascular endothelial growth factor intravitreal injections and were responsive to treatment.

Efficacy and Safety of Lampalizumab for Geographic Atrophy Due to Age-Related Macular Degeneration: Chroma and Spectri Phase 3 Randomized Clinical Trials.

Importance: Geographic atrophy (GA) secondary to age-related macular degeneration is a leading cause of visual disability in older individuals. A phase 2 trial suggested that lampalizumab, a selective complement factor D inhibitor, reduced the rate of GA enlargement, warranting phase 3 trials.

Objective: To assess the safety and efficacy of lampalizumab vs sham procedure on enlargement of GA.

The Clinical Importance of Changes in Diabetic Retinopathy Severity Score.

Purpose: To investigate the clinical importance of changes in diabetic retinopathy severity score (DRSS) in patients with diabetic macular edema (DME) treated with intravitreal ranibizumab.

Design: Post hoc analysis of the phase III RIDE and RISE studies of ranibizumab for treatment of DME.

Participants: Four hundred sixty-eight eyes treated with ranibizumab from randomization with gradable DRSS on baseline fundus photographs.

Effect of Ranibizumab on the Decision to Drive and Vision Function Relevant to Driving in Patients With Diabetic Macular Edema: Report From RESTORE, RIDE, and RISE Trials.

Importance: The potential effect of treatments for diabetic macular edema (DME) on driving should be of value to patients and clinicians, such as ophthalmologists and other physicians, who treat patients with diabetes mellitus.

Objective: To determine the effect of ranibizumab on driving and patient-reported vision function relevant to driving among patients with DME.

Design, Setting, And Participants: This exploratory post hoc analysis was conducted between October 1, 2011, and July 25, 2015, based on deidentified data from phase 3, multicenter, randomized clinical trials (RIDE, RISE, and RESTORE trials).

Outcomes with As-Needed Ranibizumab after Initial Monthly Therapy: Long-Term Outcomes of the Phase III RIDE and RISE Trials.

Purpose: To determine whether the efficacy and safety achieved with monthly ranibizumab as treatment for diabetic macular edema (DME) can be maintained with less-than-monthly treatment.

Design: Open-label extension (OLE) phase of randomized, sham-controlled phase III trials: RIDE (NCT00473382) and RISE (NCT00473330).

Participants: Five hundred of 582 adults who completed the 36-month randomized core studies elected to enter the OLE.

Effects of intravitreal ranibizumab on retinal hard exudate in diabetic macular edema: findings from the RIDE and RISE phase III clinical trials.

Purpose: To evaluate the effect of monthly intravitreal ranibizumab on hard exudate (HE) area and the impact of HE on visual acuity (VA) outcomes in diabetic macular edema (DME) patients using data from 2 phase III clinical trials.

Design: Exploratory analyses of phase III, randomized, double-masked, sham-controlled, multicenter clinical trials.

Participants: Adults with DME, baseline best-corrected VA 20/40 to 20/320 Snellen equivalent, and central foveal thickness of ≥275 μm.

Long-term effects of therapy with ranibizumab on diabetic retinopathy severity and baseline risk factors for worsening retinopathy.

Purpose: To assess the effects of intravitreal ranibizumab on diabetic retinopathy (DR) severity when administered for up to 3 years, evaluate the effect of delayed initiation of ranibizumab therapy on DR severity, and identify baseline patient characteristics associated with the development of proliferative DR (PDR).

Design: Exploratory analyses of phase III, randomized, double-masked, sham-controlled multicenter clinical trials.

Participants: Adults with diabetic macular edema (DME) (N = 759), baseline best-corrected visual acuity 20/40 to 20/320 Snellen equivalent, and central foveal thickness ≥275 μm.

Vision-related function after ranibizumab treatment for diabetic macular edema: results from RIDE and RISE.

Objective: To examine the effects of intravitreal ranibizumab (Lucentis; Genentech, Inc., South San Francisco, CA) treatment on patient-reported vision-related function, as assessed by 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) scores, in patients with visual impairment secondary to center-involved diabetic macular edema (DME).

Design: Within 2 randomized, double-masked, phase 3 clinical trials (RIDE [A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema {ME} With Center Involvement Secondary to Diabetes Mellitus; NCT00473382] and RISE [A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema {ME} With Center Involvement Secondary to Diabetes Mellitus; NCT00473330]), the NEI VFQ-25 was administered at baseline and at the 6-, 12-, 18-, and 24-month follow-up visits.

Pharmacokinetics of ranibizumab after intravitreal administration in patients with retinal vein occlusion or diabetic macular edema.

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.

Neutralization of vascular endothelial growth factor slows progression of retinal nonperfusion in patients with diabetic macular edema.

Objective: To determine the effect of suppression of vascular endothelial growth factor (VEGF) by monthly injection of ranibizumab on posterior retinal nonperfusion (RNP) in patients with diabetic macular edema (DME).

Design: Unplanned retrospective analysis of prospectively collected data from 2 randomized, sham injection-controlled, double-masked, multicenter clinical trials.

Participants: Six hundred sixty-six patients with DME.

Anti-vascular endothelial growth factor therapy for diabetic macular edema.

Diabetes mellitus is a serious health problem that affects over 350 million individuals worldwide. Diabetic retinopathy (DR), which is the most common microvascular complication of diabetes, is the leading cause of new cases of blindness in working-aged adults. Diabetic macular edema (DME) is an advanced, vision-limiting complication of DR that affects nearly 30% of patients who have had diabetes for at least 20 years and is responsible for much of the vision loss due to DR.

Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE.

Purpose: To report 36-month outcomes of RIDE (NCT00473382) and RISE (NCT00473330), trials of ranibizumab in diabetic macular edema (DME).

Design: Phase III, randomized, multicenter, double-masked, 3-year trials, sham injection-controlled for 2 years.

Participants: Adults with DME (n=759), baseline best-corrected visual acuity (BCVA) 20/40 to 20/320 Snellen equivalent, and central foveal thickness (CFT) ≥ 275 μm on optical coherence tomography.

Ranibizumab treatment outcomes in phakic versus pseudophakic eyes: an individual patient data analysis of 2 phase 3 trials.

Objective: To compare visual outcomes in phakic and pseudophakic eyes treated with monthly intravitreal ranibizumab for exudative age-related macular degeneration (AMD).

Design: Meta-analysis of individual patient data from 2 phase 3 clinical trials of intravitreal ranibizumab in neovascular AMD (Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration [ANCHOR], ClinicalTrials.gov number, NCT00061594; and Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular Age-Related Macular Degeneration [MARINA], ClinicalTrials.

Long-term effects of ranibizumab on diabetic retinopathy severity and progression.

Objective: To evaluate effects of intravitreal ranibizumab on diabetic retinopathy (DR) severity over time in 2 phase 3 clinical trials (RIDE, NCT00473382; RISE, NCT00473330) of ranibizumab for diabetic macular edema.

Methods: Participants with diabetic macular edema (n=759) were randomized to monthly sham, 0.3-mg ranibizumab, or 0.

Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE.

Purpose: To evaluate the efficacy and safety of intravitreal ranibizumab in diabetic macular edema (DME) patients.

Design: Two parallel, methodologically identical, phase III, multicenter, double-masked, sham injection-controlled, randomized studies.

Participants: Adults with vision loss from DME (best-corrected visual acuity [BCVA], 20/40-20/320 Snellen equivalent) and central subfield thickness ≥275 μm on time-domain optical coherence tomography (OCT).

Incidence of retinal pigment epithelial tears after intravitreal ranibizumab injection for neovascular age-related macular degeneration.

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 (ANti-VEGF antibody for the treatment of predominantly classic CHORoidal neovascularization in age-related macular degeneration [ANCHOR], Minimally classic/occult trial of the Anti-VEGF antibody Ranibizumab In the treatment of Neovascular Age-related macular degeneration [MARINA], and A Phase IIIb, Multicenter, Randomized, Double-Masked, Sham Injection-Controlled Study of the Efficacy and Safety of Ranibizumab 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.

Cataract surgery in ranibizumab-treated patients with neovascular age-related macular degeneration from the phase 3 ANCHOR and MARINA trials.

Purpose: To investigate whether cataract surgery was beneficial in patients with neovascular age-related macular degeneration (AMD) receiving monthly ranibizumab injections in the ANCHOR (Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in AMD) and MARINA (Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD) phase 3 trials.

Design: Retrospective analysis.

Methods: Patients were identified who underwent cataract surgery during the 2 pivotal trials.

Choroidopathy and kidney disease: a case report and review of the literature.

The patient was a 41 year-old Mexican American women who presented with a decrease in visual acuity along with periorbital and peripheral edema. She was diagnosed with bilateral serous retinal detachment and diffuse proliferative lupus nephritis. She improved considerably in hospital after treatment with corticosteroids.

Regression of effect over long-term follow-up of conductive keratoplasty to correct mild to moderate hyperopia.

Purpose: To evaluate the long-term efficacy and stability of conductive keratoplasty (CK) for low to moderate hyperopia.

Setting: Department of Ophthalmology, Stanford University School of Medicine, Stanford, California, USA.

Methods: In this prospective nonrandomized noncontrolled clinical trial, performed as part of a U.

Molecular mechanism for orienting membrane and actin dynamics to nascent cell-cell contacts in epithelial cells.

The small GTPase Rac1 has been implicated in regulation of cell migration and cell-cell adhesion in epithelial cells. Little is known, however, about the spatial and temporal coordination of Rac1 activity required to balance these competing processes. We fractionated endogenous Rac1-containing protein complexes from membranes of Madin-Darby canine kidney cells and identified three major complexes comprising a Rac1.

Spatio-temporal regulation of Rac1 localization and lamellipodia dynamics during epithelial cell-cell adhesion.

Cadherin-dependent epithelial cell-cell adhesion is thought to be regulated by Rho family small GTPases and PI 3-kinase, but the mechanisms involved are poorly understood. Using time-lapse microscopy and quantitative image analysis, we show that cell-cell contact in MDCK epithelial cells coincides with a spatio-temporal reorganization of plasma membrane Rac1 and lamellipodia from noncontacting to contacting surfaces. Within contacts, Rac1 and lamellipodia transiently concentrate at newest sites, but decrease at older, stabilized sites.