Ranibizumab for age-related macular degeneration

Cole Eye Institute, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Expert opinion on biological therapy (Impact Factor: 3.65). 03/2012; 12(3):371-81. DOI: 10.1517/14712598.2012.660523
Source: PubMed

ABSTRACT INTRODUCTION: Age-related macular degeneration (AMD) is the leading cause of blindness in patients over 50 years in the developed world. The wet form of AMD is responsible for the majority of severe vision loss. VEGF-A is a key component in the development of wet AMD. Ranibizumab is an anti-VEGF agent that has established itself as the gold standard in the treatment of neovascular AMD. Herein, we review the pharmacology, pharmacokinetics, efficacy and safety of ranibizumab. AREAS COVERED: Since its approval in 2006, ranibizumab has revolutionized the treatment of wet AMD. In two pivotal Phase III trials, MARINA and ANCHOR, ranibizumab (0.5 mg) prevented moderate visual loss in 90 and 96% of patients, respectively, and improved vision by 15 letters or more in 33 and 40% of patients, respectively. Fixed monthly dosing regimens were compared with quarterly dosing regimens in PIER and EXCITE studies and support the superiority of fixed monthly dosing. The CATT trial revealed that bevacizumab was not inferior to ranibizumab when dosed monthly. As-needed treatment regimens of ranibizumab were also found to be non-inferior to monthly ranibizumab after 1 year of follow-up. EXPERT OPINION: Ranibizumab has positively altered the treatment of wet AMD and offers hope for millions of patients.

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    ABSTRACT: Hintergrund Ziel dieser retrospektiven Studie ist eine Evaluierung des Visusverlaufs vor und nach Rezidivtherapie der feuchten altersbedingten Makuladegeneration (AMD) in einer Universitätsaugenklinik mit zuweisenden niedergelassenen Augenärzten. Material und Methoden Retrospektiv wurden Daten von Patienten mit Rezidiv analysiert, die initial an unserer Klinik wegen ihrer feuchten AMD behandelt und von niedergelassenen Augenärzten nachkontrolliert worden waren. Es folgte an unserer Klinik eine erneute intravitreale Behandlung mit Ranibizumab nach demselben PrONTO-Schema wie in der Upload-Phase. Ergebnisse Der mittlere Visus aller 100 eingeschlossenen Patientenaugen betrug vor Therapiebeginn − 0,61 ± 0,33 LogMAR und verbesserte sich auf − 0,36 ± 0,24 LogMAR (p < 0,001). Die mittlere zentrale Netzhautdicke betrug vor Therapiebeginn 291,5 ± 85,3 μm und verringerte sich nach Abschluss der Therapie auf 200,1 ± 63,7 μm (p < 0,001). Zum Zeitpunkt des Rezidivs betrug der mittlere Visus − 0,63 ± 0,33 LogMAR und verbesserte sich nach Abschluss der Therapie signifikant auf − 0,52 ± 0,28 LogMAR (p < 0,001). Die mittlere Netzhautdicke betrug zum Zeitpunkt des Rezidivs 281,2 ± 94,4 μm und verringerte sich signifikant auf 202,7 ± 59,9 μm nach Abschluss der Rezidivtherapie (p < 0,001). Schlussfolgerung Die PrONTO-Wiederbehandlungskriterien scheinen bei gutem morphologischem und funktionellem Ansprechen der behandelten Patienten unter alltäglichen Bedingungen zu weit gefasst, sodass es im Fall eines Rezidivs unter diesen Bedingungen zu einer irreversiblen Verschlechterung kommt. Dementsprechend sollten die neuen Rezidivkriterien der aktuellen DOG/BVA/DOC-Empfehlung angewendet werden.
    Der Ophthalmologe 08/2012; DOI:10.1007/s00347-012-2717-6 · 0.72 Impact Factor
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    ABSTRACT: Aberrant growth of blood vessels in the eye forms the basis of many incapacitating diseases and currently the majority of patients respond to anti-angiogenic therapies based on blocking the principal angiogenic growth factor, vascular endothelial growth factor (VEGF). While highly successful, new therapeutic targets are critical for the increasing number of individuals susceptible to retina-related pathologies in our increasingly aging population. Prostate specific membrane antigen (PSMA) is a cell surface peptidase that is absent on normal tissue vasculature but is highly expressed on the neovasculature of most solid tumors, where we have previously shown to regulate angiogenic endothelial cell invasion. Because pathologic angiogenic responses are often triggered by distinct signals, we sought to determine if PSMA also contributes to the pathologic angiogenesis provoked by hypoxia of the retina, which underlies many debilitating retinopathies. Using a mouse model of oxygen-induced retinopathy, we found that while developmental angiogenesis is normal in PSMA null mice, hypoxic challenge resulted in decreased retinal vascular pathology when compared to wild type mice as assessed by avascular area and numbers of vascular tufts/glomeruli. The vessels formed in the PSMA null mice were more organized and highly perfused, suggesting a more 'normal' phenotype. Importantly, the decrease in angiogenesis was not due to an impaired hypoxic response as levels of pro-angiogenic factors are comparable; indicating that PSMA regulation of angiogenesis is independent of VEGF. Furthermore, both systemic and intravitreal administration of a PSMA inhibitor in wild type mice undergoing OIR mimicked the PSMA null phenotype resulting in improved retinal vasculature. Our data indicate that PSMA plays a VEGF-independent role in retinal angiogenesis and that the lack of or inhibition of PSMA may represent a novel therapeutic strategy for treatment of angiogenesis-based ocular diseases.
    PLoS ONE 11/2012; 7(7):e41285. DOI:10.1371/journal.pone.0041285 · 3.53 Impact Factor
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    ABSTRACT: BACKGROUND: The goal of this retrospective study was to evaluate the development of visual acuity before and after recurrence treatment of neovascular age-related macular degeneration (AMD) in a university eye clinic with referring ophthalmologists. METHODS: Data from patients with recurrent neovascular AMD who initially had been treated for neovascular AMD and followed by referring ophthalmologists were analyzed. An intravitreal recurrence treatment with ranibizumab using the same PrONTO scheme as used in the "upload" phase followed. RESULTS: Mean best corrected visual acuity (BCVA) of all 100 patients included in the study was - 0.61 ± 0.33 LogMAR before treatment and improved to - 0.36 ± 0.24 LogMAR (p < 0.001) after "upload" therapy. Mean central retinal thickness (CRT) was 291.5 ± 85.3 μm before treatment and decreased to 200.1 ± 63.7 μm after "upload" therapy (p < 0.001). At the time of recurrence the mean BCVA was - 0.63 ± 0.33 LogMAR and improved significantly to - 0.52 ± 0.28 LogMAR (p < 0.001) after recurrence treatment. At the time of recurrence the mean CRT was 281.2 ± 94.4 μm and decreased significantly to 202.7 ± 59.9 μm after recurrence treatment (p < 0.001). CONCLUSIONS: Retreatment criteria according to the PrONTO scheme showed good morphological and functional results in the patients with recurrent neovascular AMD treated but seemed to be defined too broadly for everyday clinical use with an irreversible loss under those conditions in cases of a recurrent episode. Accordingly, the latest recurrence criteria of the DOG/BVA/DOC recommendations should be applied.
    Der Ophthalmologe 12/2012; · 0.72 Impact Factor
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