Randomized, Double-Masked, Sham-Controlled Trial of Ranibizumab for Neovascular Age-related Macular Degeneration: PIER Study Year 1

Retina Service, Wills Eye Institute, 840 Walnut Street, Philadelphia, PA 19107, USA.
American Journal of Ophthalmology (Impact Factor: 4.02). 03/2008; 145(2):239-248. DOI: 10.1016/j.ajo.2007.10.004
Source: PubMed

ABSTRACT To evaluate the efficacy and safety of ranibizumab administered monthly for three months and then quarterly in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).
Phase IIIb, multicenter, randomized, double-masked, sham injection-controlled trial in patients with predominantly or minimally classic or occult with no classic CNV lesions.
Patients were randomized 1:1:1 to 0.3 mg ranibizumab (n = 60), 0.5 mg ranibizumab (n = 61), or sham (n = 63) treatment groups. The primary efficacy endpoint was mean change from baseline visual acuity (VA) at month 12.
Mean changes from baseline VA at 12 months were -16.3, -1.6, and -0.2 letters for the sham, 0.3 mg, and 0.5 mg groups, respectively (P < or = .0001, each ranibizumab dose vs sham). Ranibizumab arrested CNV growth and reduced leakage from CNV. However, the treatment effect declined in the ranibizumab groups during quarterly dosing (e.g., at three months the mean changes from baseline VA had been gains of 2.9 and 4.3 letters for the 0.3 mg and 0.5 mg doses, respectively). Results of subgroups analyses of mean change from baseline VA at 12 months by baseline age, VA, and lesion characteristics were consistent with the overall results. Few serious ocular or nonocular adverse events occurred in any group.
Ranibizumab administered monthly for three months and then quarterly provided significant VA benefit to patients with AMD-related subfoveal CNV and was well tolerated. The incidence of serious ocular or nonocular adverse events was low.

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Available from: David M Brown, Aug 15, 2015
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    • "Although results of this and other studies with ranibizumab administered as a PRN regimen have been promising, such regimens generally place a significant burden on the clinician in terms of decision-making and have not achieved the levels of efficacy observed with monthly regimens (Biarnes et al. 2011). A quarterly dosing regimen (after three initial monthly injections) was investigated in the PIER study (Regillo et al. 2008). The results of this study indicated that quarterly ranibizumab injections were insufficient in the majority of patients to improve or even stabilize VA after the loading phase. "
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    ABSTRACT: Purpose:  To evaluate 3-year follow-up treatment outcomes with ranibizumab (Lucentis(®) ) 0.5 mg administered either monthly or quarterly on a pro re nata (PRN) basis according to a disease activity-guided monitoring and treatment algorithm. Methods:  A total of 316 treatment-naive eyes of 316 patients with exudative age-related macular degeneration met the criteria for inclusion in this retrospective, interventional case series. Patients were treated with ranibizumab 0.5 mg according to a disease activity-guided algorithm with monthly monitoring. Optical coherence tomography and fluorescein angiography were routinely used to assess disease activity: active lesions were treated with a series of three monthly injections, whereas inactive lesions were treated with quarterly injections. Results:  Mean Early Treatment Diabetic Retinopathy Study best-corrected visual acuity improved from 52 letters at baseline to 59 letters at 12 months, achieved with a mean of 7.1 injections, 61 letters at 24 months with a mean of 5.0 injections administered in the second year and 60 letters at 36 months with a mean number of 5.2 injections. Conclusions:  Monthly visits and a morphology-driven PRN regimen with 3 injections in case of recurrence plus quarterly injections in case of inactive CNV resulted in an average VA gain of 7-9 letters that could be maintained over 3 years.
    Acta ophthalmologica 06/2012; 91(6). DOI:10.1111/j.1755-3768.2012.02457.x · 2.51 Impact Factor
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    • "Since the introduction of Ranibizumab (LucentisÒ, Novartis, Basel, Switzerland), it is possible for the first time to treat neovascular AMD achieving gain of visual acuity. Ranibizumab is a recombinant monoclonal antibody fragment neutralizing all active forms of the vascular endothelial growth factor (VEGF) A and has been shown in large clinical trials to improve the course of neovascular AMD significantly (Brown et al. 2006; Regillo et al. 2008; Rosenfeld et al. 2006). Ranibizumab is FDA approved for all subtypes of CNVs because of AMD and in Germany currently injected intravitreally thrice during a period of 2 months (loading doses). "
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    ABSTRACT: To assess the interobserver variability (IOV) in indicating retreatment for neovascular Age-related macular degeneration 4 weeks after three Ranibizumab loading doses using spectral domain OCT (SD-OCT) as the primary objective diagnostic tool. Four observers decided for or against 4th Ranibizumab injection in 108 patients by six different rating rounds (RR) based on the SD-OCT findings after the loading doses. Postoperative OCT images were supplemented consecutively with information from a chart review as the 'patients subjective estimation of vision (SE)', the course of best-corrected visual acuity (BCVA) and the preoperative OCT as well as all information collectively. Agreement rates (AR) and Kappa statistics were calculated. Based on post-treatment OCT findings only (RR1), mean reinjection rate of all observers was 37.5%. Adding supplementary information, mean reinjection rate decreased to 20% when all information was available reflecting the 'real' situation (RR 6). Interobserver agreement rates varied from 66.7% to 90.7% depending on rating rounds and interobserver pairs. Mean AR and Kappa values (KV) were as following: AR 81.6%, KV 0.61 (RR1: 'only post-OP OCT'); AR 76.7%, KV 0.33 (RR2: post-OP OCT + SE); AR 80.3%, KV 0.45 (RR3: post-OP OCT + BCVA); AR 80.7%, KV 0.46 (RR4: pre- and post-OP OCT); AR 82.2%, KV 0.49 (RR5: post-OP OCT + SE + BCVA); and finally AR 83.6%, KV 0.47 (RR6: pre- and post-OP OCT + SE + BCVA). The overall mean agreement rate was 80.9% with a Kappa of 0.47. IOV for indicating retreatment after three Ranibizumab loading doses reveals only moderate agreement in Kappa statistics, which seems to be too low considering the high costs for retreatments. More concise guidelines based on the post-treatment OCT scans as the presumably most sensitive and noninvasive objective tool to follow choroidal neovascularization activity by judging the course of sub- and intraretinal fluid are necessary.
    Acta ophthalmologica 02/2012; 90(1):49-55. DOI:10.1111/j.1755-3768.2010.01940.x · 2.51 Impact Factor
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    • "We excluded 11 studies because they were evaluating adverse outcome or complications of surgical procedures (Ahmed 2002; Akman 2004; Corke 1999; Jacobi 2000; Lira 2001; Morel 2006; Nicholson 2000; Ozdemir 2004; Schein 2000; Thompson 1986; Yuen 2007). Twenty-four were RCTs which were limited to one specific population of patients with age-related visual problems: 12 included a population of patients with age-related macular degeneration (Boyer 2009; Brown 2009; Busbee 2005; Ciulla 2002; Heier 2006; Lai 2009; Michels 2005; Pulido 2006; Regillo 2008; Reichel 2007; Rosenfield 2006; Slakter 2006 ); two included a population of patients with cataracts (Harwood 2005; Uusitalo 1999 "
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    ABSTRACT: The prevalence of eye problems increases with age and, consequently, so does the level of visual impairment. As the incidence of stroke also increases with age, a significant proportion of stroke patients will have age-related visual problems. It is possible that the effect of interventions for age-related visual problems may differ in the population of stroke patients compared to the wider population of older people. The interaction between the problems arising directly from stroke and those arising directly from age-related visual problems will be complex. Interventions for age-related visual problems may also be affected by the presence of other stroke-related co-morbidities. Consequently, the nature and outcome of interventions for age-related visual problems may be different in patients with stroke. The aim of this review is to determine if interventions for age-related visual problems improve functional ability following stroke. We searched the Cochrane Stroke Group Trials Register (March 2011), the Cochrane Eyes and Vision Group Trials Register (December 2009) and nine electronic bibliographic databases including: the Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), MEDLINE (1950 to February 2011), EMBASE (1980 to February 2011), CINAHL (1982 to February 2011), AMED (1985 to February 2011) and PsycINFO (1967 to February 2011). We also searched reference lists and trials registers, handsearched journals and conference proceedings, and contacted experts. Randomised trials in adults after stroke, where the intervention is specifically targeted at assessing, treating or correcting age-related visual problems, or improving the ability of the patient to cope with visual impairment. Primary outcome was functional ability in activities of daily living and secondary outcomes included functional ability in extended activities of daily living, visual acuity, visual field, visual function, balance, falls, depression and anxiety, discharge destination/residence after stroke, quality of life and social isolation, adverse events and death. Two review authors independently screened abstracts and planned to extract data and appraise trials. We planned that assessment of methodological quality would be undertaken for allocation concealment, blinding of outcome assessor, method of dealing with missing data and other potential sources of bias. We considered 7357 titles, 460 abstracts and 85 full papers. We identified no studies for inclusion in this review. There are no implications for practice arising from this review. Evidence relating to the management of patients (from the general population) with age-related visual problems is available from other Cochrane reviews and is likely to be the best evidence available for making treatment decisions about individual patients. Subgroup analyses within these reviews to explore the effect of interventions for age-related visual problems in patients with stroke are recommended. We recommend that the objectives and selection criteria for this Cochrane review are amended and clarified prior to any future updates.
    Cochrane database of systematic reviews (Online) 01/2012; 3(3):CD008390. DOI:10.1002/14651858.CD008390.pub2 · 5.94 Impact Factor
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