Treatment Of Wet AMD Research Articles

Ocular distribution and pharmacokinetics of 125I‐OPT302 and 125I‐Aflibercept (EYLEA) following intravitreal administration to pigmented rabbits

AbstractPurpose OPT‐302 is a soluble receptor that specifically and potently blocks VEGF‐C and VEGF‐D activity which are involved in the progression of retinal and corneal diseases. OPT‐302 is currently under development for the treatment of wet AMD. The purpose of this study was to assess ocular distribution and pharmacokinetics of 125I‐OPT‐302 and 125I‐EYLEA following intravitreal (IVT)dosing in Dutch Belted rabbits.Methods 125I‐OPT‐302 and 125I‐EYLEA were prepared at ~10 mg/mL and 50 µCi/mg. Eight animals/group were dosed with 0.5 mg test article/eye. Serum and ocular tissues were collected at eight time points between 1 and 672 hours for radioanalysis. The formulations were homogeneous, stable, and active with their cognate ligands.Results Following IVT dosing the test articles were well tolerated. There was low systemic exposure of 125I‐OPT‐302 with AUC(0‐t) of 110000 ng eq*hours/mL. Systemic exposure to 125I‐EYLEA was ~4 fold greater at 420000 ng eq*hours/mL. Concentrations of 125I‐OPT‐302 and 125I‐EYLEA in the vitreous humor (VH) at C0 were 368000 and 337000 ng equivalents/g, respectively. Elimination t1/2 from VH were similar at 104 and 112 hours. For ocular tissues, the highest concentrations of radioactivity were found in retina, RPE and choroid at 1 and 12 hours postdose. Maximum concentrations were similar for each test article. Half‐lives were 104 & 102 hours in choroid and 109 & 137 hours in RPE for 125I‐OPT‐302 and 125I‐EYLEA,respectively.Conclusion 125I‐OPT‐302 and 125I‐EYLEA had prolonged exposure of posterior and anterior ocular tissues at similar concentrations for each compound, while systemic clearance of 125I‐OPT‐302 was faster than 125I‐Eylea..

Photodynamic therapy for polypoidal choroidal vasculopathy

The first effective therapy for exudative macular degeneration (AMD) was Photodynamic Therapy (PDT). Diagnosis of the disease was to a large extent by fluorescein angiography (FA). Distinguishing between the leaky choroidal neovessels (CNV) associated with exudative AMD, and the polypoidal structures associated with Polypoidal Choroidal Vasculopathy (PCV) is not always easy using FA alone. The switch to Indocyanine Green angiography helped to pinpoint PCV, and thus to study the efficacy of photodynamic therapy of this particular form of retinal disease, which is more frequently encountered among pigmented individuals. The results appear to be quite promising, and in the year following treatment only a small fraction of the patients had to be retreated. Alternatively, treating PCV with repeated intravitreal VEGF blocking agents was not as successful as it was in the treatment of wet AMD. However, combining PDT-induced angio-occlusion of the polypoidal lesions with anti-vascular endothelial growth factor therapy was shown to be quite effective, and the combination of PDT with an anti-angiogenic agent as well as a steroid, in a triple therapy, was recently also shown to be a quite promising option. In the present article we review the data on PDT of PCV, including combination therapies and alternative treatments. We also report on similarities and differences between AMD and PCV.

Cost/effectiveness study of ranibizumab versus bevacizumab in garcia de Orta hospital

BackgroundAge-related macular degeneration (AMD) is one of the main causes of blindness over the age of 50 in developed Western countries. Angiogenic growth factors, particularly vascular endothelial growth factor (VEGF),...

Comment on ‘Preclinical aspects of anti-VEGF agents for the treatment of wet AMD: ranibizumab and bevacizumab’

Comment on ‘Preclinical aspects of anti-VEGF agents for the treatment of wet AMD: ranibizumab and bevacizumab’

Patient characteristics and treatment of neovascular age-related macular degeneration in France: the LUEUR1 observational study

Age-related macular degeneration is the primary cause of blindness in developed countries. Current treatments of this degenerative disease mainly include laser, photodynamic therapy with verteporfin and administration of anti-vascular endothelial growth factors. The LUEUR (LUcentis® En Utilisation Réelle) study is composed of a cross-sectional part (LUEUR1), which examined the current management of wet AMD in France, and a follow-up part (LUEUR2), which will assess the development of patients treated for wet AMD over 4 years. Here we describe the results of LUEUR1. Patients with wet AMD were enrolled during a routine medical examination in LUEUR1, a cross-sectional, observational, prospective, multicentre study. Investigators recorded patient demographics, visual acuity, characteristics of wet AMD lesions, date of AMD diagnosis, comorbidities, previous treatments, treatments prescribed at inclusion, and low vision rehabilitation. A total of 72 investigators recruited 1,019 patients with wet AMD, corresponding to 1,405 eyes affected by the disease. The mean age of patients was 78.7 ± 7.3 years. Most were female (62.3%) and non-smokers (66.9%). The mean visual acuity was 49.12 ± 24.18 Early Treatment Diabetic Retinopathy Study letters. Most eyes showed occult (52.8%) and subfoveal (84.6%) choroidal neovascularisation. Bilateral wet AMD affected 37.9% of patients. The median time since diagnosis was 12 months. Ranibizumab-based therapy (67.3%) and photodynamic therapy (29.8%) were the most frequent previous treatments. Prior to inclusion, 5.6% of patients had low vision rehabilitation. When a treatment was prescribed on the day of inclusion, it was most often ranibizumab (89.0% of all treatments at inclusion). The results of this study illustrate the impact of anti-vascular endothelial growth factor therapies on the treatment of wet AMD in a real-life context. Specifically, ranibizumab-based therapy appears to have largely replaced laser photocoagulation and verteporfin-based photodynamic therapy.

DEVELOPMENT OF RANIBIZUMAB, AN ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR ANTIGEN BINDING FRAGMENT, AS THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION

Angiogenesis is a key aspect of the wet form of age-related neovascular (AMD), the leading cause of blindness in the elderly population. Substantial evidence indicated that vascular endothelial growth factor (VEGF)-A is a major mediator of angiogenesis and vascular leakage in wet AMD. VEGF-A is the prototype member of a gene family that includes also PlGF, VEGF-B, VEGF-C, VEGF-D and the orf virus-encoded VEGF-E. Several isoforms of VEGF-A can be generated due to alternative mRNA splicing. Various VEGF inhibitors have been clinically developed. Among these, ranibizumab is a high affinity recombinant Fab that neutralizes all isoforms of VEGF-A. The article briefly reviews the biology of VEGF and then focuses on the path that led to clinical development of ranibizumab. The safety and efficacy of ranibizumab in the treatment of neovascular AMD have been evaluated in two large phase III, multicenter, randomized, double-masked, controlled pivotal trials in different neovascular AMD patient populations. Combined, the trial results indicate that ranibizumab results not only in a slowing down of vision loss but also in a significant proportion of patients experiencing a clinically meaningful vision gain. The visual acuity benefit over control was observed regardless of CNV lesion type. Furthermore, the benefit was associated with a low rate of serious adverse events. Ranibizumab represents a novel therapy that, for the first time, appears to have the potential to enable many AMD patients to obtain a meaningful and sustained gain of vision. On June 30 2006, ranibizumab was approved by the US Food and Drug Administration for the treatment of wet AMD.