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      Real-world visual acuity outcomes between ranibizumab and aflibercept in treatment of neovascular AMD in a large US data set

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      1 , 2 , * , 3 , 4 , 4 , 5
      Eye
      Nature Publishing Group

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          Abstract

          Purpose

          To examine 12-month real-world visual acuity outcomes and treatment patterns in neovascular age-related macular degeneration (nAMD) eyes, including those with pigment epithelial detachment (PED), receiving ranibizumab or aflibercept.

          Patients and methods

          Electronic medical records were used to identify ranibizumab or aflibercept-treated nAMD eyes with 12 months follow-up from first prescription. The primary objective was to compare mean change in visual acuity (VA) between index and month 12, in eyes treated with ranibizumab and aflibercept to assess the non-inferiority of ranibizumab vs aflibercept using a −5 letter non-inferiority margin. The number of injections and non-injection visits during follow-up were key secondary objectives.

          Results

          A total of 3350 ranibizumab and 4300 aflibercept treatment-naive eyes were included. At month 12, mean change from index in VA letter score was −0.30 for ranibizumab and −0.19 for aflibercept ( P=0.81). The adjusted difference of mean change was −0.14 (−0.79 to 0.51) ( P=0.67) (generalized estimating equations method) confirming the non-inferiority of ranibizumab. Eyes received a similar number of injections during follow-up. The mean (±SD) number of ranibizumab and aflibercept injections were 6.70 (±2.54) and 7.00 (±2.40), respectively ( P<0.0001). In PED eyes, the mean (±SD) change between baseline to month 12 was 1.25 (±11.3) for ranibizumab and −0.39 (±13.3) for aflibercept (adjusted between-group difference 1.80 (−0.71 to 4.30; P=0.16)) achieved with a mean (±SD) 7.85 (±2.68) ranibizumab and 7.47 (±2.45) aflibercept injections, ( P=0.11).

          Conclusions

          Ranibizumab and aflibercept treatment yielded comparable VA outcomes in nAMD eyes, including those with PED, with similar treatment patterns over 12 months in real-world clinical practice.

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          Most cited references27

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          Ranibizumab and bevacizumab for neovascular age-related macular degeneration.

          Clinical trials have established the efficacy of ranibizumab for the treatment of neovascular age-related macular degeneration (AMD). In addition, bevacizumab is used off-label to treat AMD, despite the absence of similar supporting data. In a multicenter, single-blind, noninferiority trial, we randomly assigned 1208 patients with neovascular AMD to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation. The primary outcome was the mean change in visual acuity at 1 year, with a noninferiority limit of 5 letters on the eye chart. Bevacizumab administered monthly was equivalent to ranibizumab administered monthly, with 8.0 and 8.5 letters gained, respectively. Bevacizumab administered as needed was equivalent to ranibizumab as needed, with 5.9 and 6.8 letters gained, respectively. Ranibizumab as needed was equivalent to monthly ranibizumab, although the comparison between bevacizumab as needed and monthly bevacizumab was inconclusive. The mean decrease in central retinal thickness was greater in the ranibizumab-monthly group (196 μm) than in the other groups (152 to 168 μm, P=0.03 by analysis of variance). Rates of death, myocardial infarction, and stroke were similar for patients receiving either bevacizumab or ranibizumab (P>0.20). The proportion of patients with serious systemic adverse events (primarily hospitalizations) was higher with bevacizumab than with ranibizumab (24.1% vs. 19.0%; risk ratio, 1.29; 95% confidence interval, 1.01 to 1.66), with excess events broadly distributed in disease categories not identified in previous studies as areas of concern. At 1 year, bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to the same schedule. Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly. Differences in rates of serious adverse events require further study. (Funded by the National Eye Institute; ClinicalTrials.gov number, NCT00593450.).
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            Causes and prevalence of visual impairment among adults in the United States.

            To estimate the cause-specific prevalence and distribution of blindness and low vision in the United States by age, race/ethnicity, and gender, and to estimate the change in these prevalence figures over the next 20 years. Summary prevalence estimates of blindness (both according to the US definition of < or =6/60 [< or =20/200] best-corrected visual acuity in the better-seeing eye and the World Health Organization standard of < 6/120 [< 20/400]) and low vision (< 6/12 [< 20/40] best-corrected vision in the better-seeing eye) were prepared separately for black, Hispanic, and white persons in 5-year age intervals starting at 40 years. The estimated prevalences were based on recent population-based studies in the United States, Australia, and Europe. These estimates were applied to 2000 US Census data, and to projected US population figures for 2020, to estimate the number of Americans with visual impairment. Cause-specific prevalences of blindness and low vision were also estimated for the different racial/ethnic groups. Based on demographics from the 2000 US Census, an estimated 937 000 (0.78%) Americans older than 40 years were blind (US definition). An additional 2.4 million Americans (1.98%) had low vision. The leading cause of blindness among white persons was age-related macular degeneration (54.4% of the cases), while among black persons, cataract and glaucoma accounted for more than 60% of blindness. Cataract was the leading cause of low vision, responsible for approximately 50% of bilateral vision worse than 6/12 (20/40) among white, black, and Hispanic persons. The number of blind persons in the US is projected to increase by 70% to 1.6 million by 2020, with a similar rise projected for low vision. Blindness or low vision affects approximately 1 in 28 Americans older than 40 years. The specific causes of visual impairment, and especially blindness, vary greatly by race/ethnicity. The prevalence of visual disabilities will increase markedly during the next 20 years, owing largely to the aging of the US population.
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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

                Journal
                Eye (Lond)
                Eye (Lond)
                Eye
                Nature Publishing Group
                0950-222X
                1476-5454
                December 2017
                21 July 2017
                1 December 2017
                : 31
                : 12
                : 1697-1706
                Affiliations
                [1 ]Eye Unit, University Hospital Southampton NHS Foundation Trust , Southampton, UK
                [2 ]Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton , Southampton, UK
                [3 ]QuintilesIMS , Cambridge, MA, USA
                [4 ]Novartis Pharma AG , Basel, Switzerland
                [5 ]Retinal Consultants of Arizona LTD , Phoenix, AZ, USA
                Author notes
                [* ]Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton , Southampton, UK Tel: +44 (0) 2381 20 5049; Fax: +44 (0) 2381 20 6085. E-mail: a.j.lotery@ 123456soton.ac.uk
                Author information
                http://orcid.org/0000-0001-5541-4305
                Article
                eye2017143
                10.1038/eye.2017.143
                5733295
                28731052
                b4a3df5f-a3b2-4f56-a817-e781b221e53a
                Copyright © 2017 The Author(s)

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/

                History
                : 01 March 2017
                : 13 June 2017
                Categories
                Clinical Study

                Vision sciences
                Vision sciences

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