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: 3.87). 03/2008; 145(2):239-248. DOI: 10.1016/j.ajo.2007.10.004
Source: PubMed


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.

Download full-text


Available from: David M Brown
  • Source
    • "The PIER study, a phase 3b trial, included 182 patients with all lesion types and evaluated the efficacy and safety of monthly ranibizumab at three doses followed by dosing every 3 months. While patients in the sham group lost a mean of 16 letters during 12 months of follow-up, patients receiving either dose of ranibizumab remained stable at baseline VA.66 Ninety per cent in the group receiving the 0.5 dose lost <15 letters compared with 49% in the sham group; 13% versus 10% gained >15 letters.73 As the overall VA, returned to baseline from month 3 to month 12 after switching to quarterly dosing, this reduction appears to suggest that quarterly dosing is inferior to monthly dosing. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Age-related macular degeneration (AMD) is still referred to as the leading cause of severe and irreversible visual loss world-wide. The disease has a profound effect on quality of life of affected individuals and represents a major socioeconomic challenge for societies due to the exponential increase in life expectancy and environmental risks. Advances in medical research have identified vascular endothelial growth factor (VEGF) as an important pathophysiological player in neovascular AMD and intraocular inhibition of VEGF as one of the most efficient therapies in medicine. The wide introduction of anti-VEGF therapy has led to an overwhelming improvement in the prognosis of patients affected by neovascular AMD, allowing recovery and maintenance of visual function in the vast majority of patients. However, the therapeutic benefit is accompanied by significant economic investments, unresolved medicolegal debates about the use of off-label substances and overwhelming problems in large population management. The burden of disease has turned into a burden of care with a dissociation of scientific advances and real-world clinical performance. Simultaneously, ground-breaking innovations in diagnostic technologies, such as optical coherence tomography, allows unprecedented high-resolution visualisation of disease morphology and provides a promising horizon for early disease detection and efficient therapeutic follow-up. However, definite conclusions from morphologic parameters are still lacking, and valid biomarkers have yet to be identified to provide a practical base for disease management. The European Society of Retina Specialists offers expert guidance for diagnostic and therapeutic management of neovascular AMD supporting healthcare givers and doctors in providing the best state-of-the-art care to their patients. Trial registration number NCT01318941.
    Full-text · Article · Sep 2014 · British Journal of Ophthalmology
  • Source
    • "The PIER study reported no ocular AEs such as endophthalmitis, uveitis, vitreous hemorrhage, rhegmatogenous retinal detachment, retinal tear, or lens damage.93,124 The rate of thromboembolic events was 0% in the ranibizumab group in the first year of the study,124 and 1.7% only for the 0.3 mg group in the second year.93 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Degenerative ocular conditions, such as age-related macular degeneration, diabetic retinopathy, retinal vein occlusions, and myopic degeneration, have become a major public health problem and a leading cause of blindness in developed countries. Anti-vascular endothelial growth factor (VEGF) drugs seem to be an effective and safe treatment for these conditions. Ranibizumab, a humanized monoclonal antibody antigen-binding fragment, which inhibits all biologically active isoforms of VEGF-A, is still the gold standard treatment for the majority of these pathological entities. In this review, we present the results of the most important clinical trials concerning the efficacy and safety of ranibizumab for the treatment of degenerative ocular conditions.
    Full-text · Article · Jun 2014 · Clinical ophthalmology (Auckland, N.Z.)
    • "Antiangiogenic therapies, such as ranibizumab (Lucentis®, Genentech Inc., South San Francisco, CA) and bevacizumab (Avastin®, Genentech Inc.), have revolutionized the management of age-related macular degeneration (AMD).[12345] "
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: To describe retinal changes during Spectral Domain Optical Coherence Tomography (SD-OCT) guided bevacizumab treatment for neovascular age- related macular degeneration (AMD). Settings and Design: Single center observational study. Materials and Methods: We confirmed wet AMD in 47 eyes of 45 patients by fluorescein angiography and SD-OCT. After bevacizumab injection, we examined the patients at 4-week intervals. During each follow-up control, we performed SD-OCT and a complete ophthalmic examination. Criteria for reinjection were visual acuity loss of more than five ETDRS letters, and/or increase of central retinal thickness, sub-retinal fluid, intra-retinal fluid, pigment epithelium detachment. If reinjection criteria were not met, we advised the patient to return in 4 weeks' time for the next scheduled follow-up. We used 3-dimensional SD-OCT to measure photoreceptor defects and sub-retinal fibrosis. The main efficacy endpoints were the SD-OCT measurements of the size of photoreceptor defects, the size of external membrane defects and the central retinal thickness. Results: Over the 12 months study period, the percentage of scans in 3-D imaging mode showing visible defects of the junction between inner and outer segments of photoreceptors increased from 38.96 to 53.8%. The percentage of scans in 3-D imaging mode with visible sub-retinal fibrosis increased from 33 to 52% and mean central retinal thickness decreased from 333 μm (96-900 μm) to 272 μm (P = 0.011). Conclusion: In long-term anti- Vascular endothelial growth factor (VEGF) treatment for neovascular AMD, photoreceptor defects and fibrosis progress despite a decrease in central retinal thickness and improvements in visual acuity. We would encourage further discussion as to whether this is the natural course of the disease or a result of the treatment.
    No preview · Article · May 2014 · Indian Journal of Ophthalmology
Show more