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      Functional and anatomical outcome of eyes with neovascular age-related macular degeneration treated with intravitreal ranibizumab following an exit strategy regimen

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          Abstract

          Aims

          To assess the functional and morphological outcome of eyes with neovascular AMD treated with intravitreal ranbizumab following an exit strategy treatment regime.

          Methods

          The Bern treatment regime for neovascular AMD has a fixed injection schedule, even in the non-active stage of the disease. The regimen has been adapted from the PIER study treatment protocol. Eyes with non-active AMD will receive 4 injections in the first year, and 2 injections in the second year of follow-up before treatment stops. Patients that received ranibizumab for treatment and reached the exit criteria were identified, and charts were reviewed to assess functional and morphological outcome.

          Results

          Only 2.6% of all patients (15 out of 575 patients) reached the exit criteria. Mean change in best corrected ETDRS visual acuity (VA) was 4.5±16.9 letters when comparing baseline VA to 4 weeks after the last injection (p=0.32). OCT mean foveal thickness was significantly thinner after last treatment (247.9±43.0 µm) compared to baseline (332.5±83.1 µm, p=0.002). The mean total number of ranibizumab injections was 15.6±8.0, and the mean total treatment period was 40.9±18.3 months. Twenty percent of eyes had geographic atrophy present at baseline versus 46.6% at the end of treatment.

          Conclusions

          Even with a fixed treatment regime and a defined treatment exit strategy, only a small percentage of patients reach exit criteria. Retinal thickness has been significantly reduced by repeated intravitreal ranibizumab injections, and geographic atrophy became more frequent.

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          Most cited references7

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          Prevalence of age-related macular degeneration in the United States.

          To estimate the prevalence and distribution of age-related macular degeneration (AMD) in the United States by age, race/ethnicity, and gender. Summary prevalence estimates of drusen 125 microm or larger, neovascular AMD, and geographic atrophy were prepared separately for black and white persons in 5-year age intervals starting at 40 years. The estimated rates were based on a meta-analysis of recent population-based studies in the United States, Australia, and Europe. These rates were applied to 2000 US Census data and to projected US population figures for 2020 to estimate the number of the US population with drusen and AMD. The overall prevalence of neovascular AMD and/or geographic atrophy in the US population 40 years and older is estimated to be 1.47% (95% confidence interval, 1.38%-1.55%), with 1.75 million citizens having AMD. The prevalence of AMD increased dramatically with age, with more than 15% of the white women older than 80 years having neovascular AMD and/or geographic atrophy. More than 7 million individuals had drusen measuring 125 microm or larger and were, therefore, at substantial risk of developing AMD. Owing to the rapidly aging population, the number of persons having AMD will increase by 50% to 2.95 million in 2020. Age-related macular degeneration was far more prevalent among white than among black persons. Age-related macular degeneration affects more than 1.75 million individuals in the United States. Owing to the rapid aging of the US population, this number will increase to almost 3 million by 2020.
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            An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration.

            To evaluate an optical coherence tomography (OCT)-guided, variable-dosing regimen with intravitreal ranibizumab for the treatment of patients with neovascular age-related macular degeneration (AMD). Open-label, prospective, single-center, nonrandomized, investigator-sponsored clinical study. In this two-year study, neovascular AMD patients with subfoveal choroidal neovascularization (CNV) (n = 40) and a central retinal thickness of at least 300 microm as measured by OCT were enrolled to receive three consecutive monthly intravitreal injections of ranibizumab (0.5 mg). Thereafter, retreatment with ranibizumab was performed if one of the following changes was observed between visits: a loss of five letters in conjunction with fluid in the macula as detected by OCT, an increase in OCT central retinal thickness of at least 100 microm, new-onset classic CNV, new macular hemorrhage, or persistent macular fluid detected by OCT at least one month after the previous injection of ranibizumab. At month 12, the mean visual acuity improved by 9.3 letters (P < .001) and the mean OCT central retinal thickness decreased by 178 microm (P < .001). Visual acuity improved 15 or more letters in 35% of patients. These visual acuity and OCT outcomes were achieved with an average of 5.6 injections over 12 months. After a fluid-free macula was achieved, the mean injection-free interval was 4.5 months before another reinjection was necessary. This OCT-guided, variable-dosing regimen with ranibizumab resulted in visual acuity outcomes similar to the Phase III clinical studies, but required fewer intravitreal injections. OCT appears useful for determining when retreatment with ranibizumab is necessary.
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              Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER Study year 1.

              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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                Author and article information

                Journal
                Br J Ophthalmol
                Br J Ophthalmol
                bjophthalmol
                bjo
                The British Journal of Ophthalmology
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                0007-1161
                1468-2079
                September 2014
                29 April 2014
                : 98
                : 9
                : 1197-1200
                Affiliations
                Department of Ophthalmology, Inselspital, Bern University Hospital, and University of Bern , Bern, Switzerland
                Author notes
                [Correspondence to ] Dr Marcel N Menke, Reinhardweg 6, 3422 Kirchberg, BE, Switzerland; marcel.menke@ 123456gmail.com
                Article
                bjophthalmol-2013-304775
                10.1136/bjophthalmol-2013-304775
                4145413
                24782472
                235a1297-86be-4f60-ae41-51eaec7855fb
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

                History
                : 11 December 2013
                : 4 March 2014
                : 20 March 2014
                Categories
                1506
                Clinical Science
                Custom metadata
                unlocked

                Ophthalmology & Optometry
                macula,neovascularisation,pharmacology,retina,treatment medical
                Ophthalmology & Optometry
                macula, neovascularisation, pharmacology, retina, treatment medical

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