Safety and Efficacy of Ranibizumab in Diabetic Macular Edema (RESOLVE Study*): A 12-month, randomized, controlled, double-masked, multicenter phase II study

The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center

The effects of a flexible visual acuity-driven ranibizumab treatment regimen in age-related macular degeneration: outcomes of a drug and disease model

Differences in treatment responses to ranibizumab injections observed within trials involving monthly (MARINA and ANCHOR studies) and quarterly (PIER study) treatment suggest that an individualized treatment regimen may be effective in neovascular age-related macular degeneration. In the present study, a drug and disease model was used to evaluate the impact of an individualized, flexible treatment regimen on disease progression

Outcomes following three-line vision loss during treatment of neovascular age-related macular degeneration : subgroup analyses from MARINA and ANCHOR

This study aims to assess the impact of continued ranibizumab treatment for neovascular age-related macular degeneration on patients from the MARINA and ANCHOR randomised clinical studies who lost ? 3 lines of best-corrected visual acuity (BCVA) at any time during the first year of treatment

Examiner

single-output = MISO) ermöglicht die Nutzung der räumlichen Dimension von Funkkanälen. Strahlformung fokussiert die Charakteristik einer Antennengruppe in eine bestimmte Richtung und erhöht dadurch die Signalleistung. Räumliche Diversität, die die Zuverlässigkeit einer Funkverbindung verbessert, entsteht durch räumliche Kopien des Funksignals. Durch den Einsatz einer zusätzlichen Antennengruppe am zweiten Ende der Funkverbindung (multipleinput multiple-output=MIMO) können mehrere Signalströme im räumlichen Multiplex-Verfahren parallel übertragen werden. Der erste Teil dieser Dissertation beschäftigt sich mit MISO-Kanälen. Da sich Signalgewinn durch Strahlformung und räumliche Diversität gegenseitig widersprechen, ist es wichtig eine optimale Balance zwischen diesen beiden Techniken zu finden. Die optimale Balance hängt sowohl von den Kanaleigenschaften und dem Wissen darüber ab, als auch von den Anforderungen an Datenrate und erlaubter Bitfehlerquote. Zum einen erläutere ich wieviel Gewinn durch Strahlformung und durch Diversität erreichbar ist, wenn man (i) nichts über den Kanal weiß, (ii) die Statistik zweiter Ordnung des Kanals kennt, oder (iii) vollständiges Kanalwissen vorliegt. Zum anderen konzentriere ich mich auf den Fall einer Antennengruppe bei einem Sender

Single-Chain Antibody Fragment VEGF Inhibitor RTH258 for Neovascular Age-Related Macular Degeneration:A Randomized Controlled Study

PurposeTo assess the safety and efficacy of different doses of RTH258 applied as single intravitreal administration compared with ranibizumab 0.5 mg in patients with neovascular age-related macular degeneration (AMD).DesignSix-month, phase 1/2, prospective, multicenter, double-masked, randomized, ascending single-dose, active-controlled, parallel-group study.ParticipantsA total of 194 treatment-naive patients, aged ≥50 years, with primary subfoveal choroidal neovascularization secondary to AMD.MethodsPatients received a single intravitreal injection of RTH258 0.5 mg (n = 11), 3.0 mg (n = 31), 4.5 mg (n = 47), or 6.0 mg (n = 44), or ranibizumab 0.5 mg (n = 61).Main Outcome MeasuresThe primary efficacy end point was the change from baseline to month 1 in central subfield thickness (CSFT) measured by spectral-domain optical coherence tomography. The secondary efficacy end point was the duration of treatment effect measured as time from the initial injection to receipt of post-baseline therapy (PBT) guided by protocol-defined criteria. Adverse events (AEs) were recorded throughout the study.ResultsRTH258 demonstrated noninferiority compared with ranibizumab in mean change in CSFT from baseline to month 1 for the 4.5- and 6.0-mg dose groups (margin: 40 μm, 1-sided alpha 0.05). The difference in CSFT change at month 1 comparison with ranibizumab was 22.86 μm (90% confidence interval [CI], −9.28 to 54.99) and 19.40 μm (95% CI, −9.00 to 47.80) for RTH258 4.5 and 6 mg, respectively. The median time to PBT after baseline therapy was 60 and 75 days for patients in the RTH258 4.5- and 6.0-mg groups, respectively, compared with 45 days for ranibizumab. Changes in best-corrected visual acuity with RTH258 were comparable to those observed with ranibizumab. The most frequent AEs reported for the RTH258 groups were conjunctival hemorrhage, eye pain, and conjunctival hyperemia; the majority of these events were mild in intensity.ConclusionsThis first-in-human study of RTH258 demonstrated noninferiority in the change in CSFT at 1 month for the 4.5- and 6.0-mg doses compared with ranibizumab and an increase of 30 days in the median time to PBT for the 6.0-mg dose. There were no unexpected safety concerns, and the results support the continued development of RTH258 for the treatment of neovascular AMD

Efficacy and Safety of Monthly versus Quarterly Ranibizumab Treatment in Neovascular Age-related Macular Degeneration: The EXCITE Study

Objective: To demonstrate noninferiority of a quarterly treatment regimen to a monthly regimen of ranibizumab in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Design: A 12-month, multicenter, randomized, double-masked, active-controlled, phase IIIb study. Participants: Patients with primary or recurrent subfoveal CNV secondary to AMD (353 patients), with predominantly classic, minimally classic, or occult (no classic component) lesions. Intervention: Patients were randomized (1:1:1) to 0.3 mg quarterly, 0.5 mg quarterly, or 0.3 mg monthly doses of ranibizumab. Treatment comprised of a loading phase (3 consecutive monthly injections) followed by a 9-month maintenance phase (either monthly or quarterly injection). Main Outcome Measures: Mean change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to month 12 and the incidence of adverse events (AEs). Results: In the per-protocol population (293 patients), BCVA, measured by Early Treatment Diabetic Retinopathy Study-like charts, increased from baseline to month 12 by 4.9, 3.8, and 8.3 letters in the 0.3 mg quarterly (104 patients), 0.5 mg quarterly (88 patients), and 0.3 mg monthly (101 patients) dosing groups, respectively. Similar results were observed in the intent-to-treat (ITT) population (353 patients). The mean decrease in CRT from baseline to month 12 in the ITT population was -96.0 mu m in 0.3 mg quarterly, -105.6 mu m in 0.5 mg quarterly, and -105.3 mu m in 0.3 mg monthly group. The most frequent ocular AEs were conjunctival hemorrhage (17.6%, pooled quarterly groups; 10.4%, monthly group) and eye pain (15.1%, pooled quarterly groups; 20.9%, monthly group). There were 9 ocular serious AEs and 3 deaths; 1 death was suspected to be study related (cerebral hemorrhage; 0.5 mg quarterly group). The incidences of key arteriothromboembolic events were low. Conclusions: After 3 initial monthly ranibizumab injections, both monthly (0.3 mg) and quarterly (0.3 mg/0.5 mg) ranibizumab treatments maintained BCVA in patients with CNV secondary to AMD. At month 12, BCVA gain in the monthly regimen was higher than that of the quarterly regimens. The noninferiority of a quarterly regimen was not achieved with reference to 5.0 letters. The safety profile was similar to that reported in prior ranibizumab studies. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2011; 118: 831-839 (C) 2011 by the American Academy of Ophthalmolog

The RESTORE Study Ranibizumab Monotherapy or Combined with Laser versus Laser Monotherapy for Diabetic Macular Edema

Objective: To demonstrate superiority of ranibizumab 0.5 mg monotherapy or combined with laser over laser alone based on mean average change in best-corrected visual acuity (BCVA) over 12 months in diabetic macular edema (DME). Design: A 12-month, randomized, double-masked, multicenter, laser-controlled phase III study. Participants: We included 345 patients aged >= 18 years, with type 1 or 2 diabetes mellitus and visual impairment due to DME. Methods: Patients were randomized to ranibizumab + sham laser (n = 116), ranibizumab + laser (n = 118), or sham injections + laser (n = 111). Ranibizumab/sham was given for 3 months then pro re nata (PRN); laser/sham laser was given at baseline then PRN (patients had scheduled monthly visits). Main Outcome Measures: Mean average change in BCVA from baseline to month 1 through 12 and safety. Results: Ranibizumab alone and combined with laser were superior to laser monotherapy in improving mean average change in BCVA letter score from baseline to month 1 through 12 (+6.1 and +5.9 vs +0.8; both P = 15 and BCVA letter score level >73 (20/40 Snellen equivalent) with ranibizumab (22.6% and 53%, respectively) and ranibizumab + laser (22.9% and 44.9%) versus laser (8.2% and 23.6%). The mean central retinal thickness was significantly reduced from baseline with ranibizumab (-118.7 mu m) and ranibizumab + laser (-128.3 mu m) versus laser (-61.3 mu m; both P <0.001). Health-related quality of life, assessed through National Eye Institute Visual Function Questionnaire (NEI VFQ-25), improved significantly from baseline with ranibizumab alone and combined with laser (P <0.05 for composite score and vision-related subscales) versus laser. Patients received similar to 7 (mean) ranibizumab/sham injections over 12 months. No endophthalmitis cases occurred. Increased intraocular pressure was reported for 1 patient each in the ranibizumab arms. Ranibizumab monotherapy or combined with laser was not associated with an increased risk of cardiovascular or cerebrovascular events in this study. Conclusions: Ranibizumab monotherapy and combined with laser provided superior visual acuity gain over standard laser in patients with visual impairment due to DME. Visual acuity gains were associated with significant gains in VFQ-25 scores. At 1 year, no differences were detected between the ranibizumab and ranibizumab + laser arms. Ranibizumab monotherapy and combined with laser had a safety profile in DME similar to that in age-related macular degeneration. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2011; 118: 615-625 (C) 2011 by the American Academy of Ophthalmolog