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      Predictive models of long-term anatomic outcome in age-related macular degeneration treated with as-needed Ranibizumab

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          Abstract

          Background

          To analyze predictors and develop predictive models of anatomic outcome in neovascular age-related macular degeneration (AMD) treated with as-needed ranibizumab after 4 years of follow-up.

          Methods

          A multicenter consecutive case series non-interventional study was performed. Clinical, funduscopic and OCT characteristics of 194 treatment-naïve patients with AMD treated with as-needed ranibizumab for at least 2 years and up to 4 years were analyzed at baseline, 3 months and each year until the end of the follow-up. Baseline demographic and angiographic characteristics were also evaluated. R Statistical Software was used for statistical analysis. Main outcome measure was final anatomic status.

          Results

          Factors associated with less probability of preserved macula were diagnosis in 2009, older age, worse vision, presence of atrophy/fibrosis, pigment epithelium detachment, and geographic atrophy/fibrotic scar/neovascular AMD in the fellow eye. Factors associated with higher probability of GA were presence of atrophy and greater number of injections, whereas male sex, worse vision, lesser change in central macular thickness and presence of fibrosis were associated with less probability of GA as final macular status. Predictive model of preserved macula vs. GA/fibrotic scar showed sensibility of 77.78% and specificity of 69.09%. Predictive model of GA vs. fibrotic scar showed sensibility of 68.89% and specificity of 72.22%.

          Conclusions

          We identified predictors of final macular status, and developed two predictive models. Predictive models that we propose are based on easily harvested variables, and, if validated, could be a useful tool for individual patient management and clinical research studies.

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          Most cited references19

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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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            An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group.

            A common detection and classification system is needed for epidemiologic studies of age-related maculopathy (ARM). Such a grading scheme for ARM is described in this paper. ARM is defined as a degenerative disorder in persons > or = 50 years of age characterized on grading of color fundus transparencies by the presence of the following abnormalities in the macular area: soft drusen > or = 63 microns, hyperpigmentation and/or hypopigmentation of the retinal pigment epithelium (RPE), RPE and associated neurosensory detachment, (peri)retinal hemorrhages, geographic atrophy of the RPE, or (peri)retinal fibrous scarring in the absence of other retinal (vascular) disorders. Visual acuity is not used to define the presence of ARM. Early ARM is defined as the presence of drusen and RPE pigmentary abnormalities described above; late ARM is similar to age-related macular degeneration (AMD) and includes dry AMD (geographic atrophy of the RPE in the absence of neovascular AMD) or neovascular AMD (RPE detachment, hemorrhages, and/or scars as described above). Methods to take and grade fundus transparencies are described.
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              Novel method for analyzing snellen visual acuity measurements.

              Most retrospective reviews convert Snellen visual acuity measurements obtained during routine clinic visits to logarithm of the minimum angle of resolution (logMAR) units so that statistical manipulations can be performed. However, visual acuity measurements expressed as logMAR units are not intuitively interpretable by clinicians. A more intuitive approach is presented here which uses the conversion of Snellen visual acuity fractions to Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores for statistical manipulations. Snellen visual acuity measurements were converted to approximate ETDRS (approxETDRS) letter scores for statistical manipulations and then converted back to Snellen equivalent fractions. The formula to convert Snellen visual acuity measurements to approxETDRS letter scores is 85 + 50 x log (Snellen fraction), which may be rounded to the nearest letter. A linear relationship exists between true ETDRS letter scores, approxETDRS letter scores, and logMAR units. The interconversion between Snellen visual acuity measurements, logMAR units, and approxETDRS letter scores was prepared in a tabular form for easy reference. The same outcomes (in Snellen fractions) were obtained with statistical manipulation of either approxETDRS letter scores or logMAR conversions. Conversion of Snellen visual acuity fractions to approxETDRS letter scores for the purpose of performing statistical manipulations provides more readily interpretable outcomes compared with the current strategy of converting Snellen visual acuity fractions to logMAR units.
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                Author and article information

                Contributors
                34 983 42 35 59 , luciaglezbuendia@gmail.com
                sdelgadotirado@gmail.com
                rsanabria@ioba.med.uva.es
                itziar.fernandez@ioba.med.uva.es
                rosa@ioba.med.uva.es
                Journal
                BMC Ophthalmol
                BMC Ophthalmol
                BMC Ophthalmology
                BioMed Central (London )
                1471-2415
                18 August 2017
                18 August 2017
                2017
                : 17
                : 147
                Affiliations
                [1 ]ISNI 0000 0001 2286 5329, GRID grid.5239.d, Instituto de Oftalmobiologia Aplicada (IOBA), , Campus Miguel Delibes, University of Valladolid, ; P° de Belén n° 17, 47011 Valladolid, Spain
                [2 ]Clinic University Hospital of Valladolid, Valladolid, Spain
                [3 ]Health Complex of Palencia, Palencia, Spain
                [4 ]Ciber BBN, Zaragoza, Spain
                Article
                544
                10.1186/s12886-017-0544-x
                5563005
                28821236
                c96efd47-3bab-4f24-9f37-3a55348a2619
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 2 January 2017
                : 9 August 2017
                Funding
                Funded by: Novartis-Spain
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Ophthalmology & Optometry
                age-related macular degeneration,choroidal neovascularization,anti-vegf

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