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      Visual acuity outcomes and anti-VEGF therapy intensity in diabetic macular oedema: a real-world analysis of 28 658 patient eyes

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          Abstract

          Background/Aim

          To assess visual acuity (VA) outcomes and antivascular endothelial growth factor (anti-VEGF) treatment intensity in diabetic macular oedema (DMO).

          Methods

          Retrospective analysis was performed in treatment-naïve patients with DMO from 2013 to 2018 using a database of aggregated de-identified electronic medical records (Vestrum Health).

          Results

          At 1 year, 28 658 patient eyes underwent a mean of 6.4 anti-VEGF injections, gaining a mean of +4.2 letters (95% confidence interval for mean gain: +4.0 to +4.5 letters, p<0.001). When stratified by anti-VEGF medication and by years 2013–2018, no clinically meaningful differences in injection frequency or 1-year VA change resulted. At 1 year, 50% of eyes received ≤6 injections, while <20% received 10–13 injections, representing monthly treatment. Mean letters gained at 1 year generally showed a linear relationship with mean number of anti-VEGF injections, beyond two injections. Eyes with good baseline VA (≥20/40) generally were at risk of VA loss at 1 year; those with moderately severe baseline impairment (20/70 to 20/200) who received ≥10 injections improved by a mean of +10.3 letters.

          Conclusion

          In clinical practice, patients with DMO undergo fewer anti-VEGF injections and exhibit worse visual gains compared with patients in randomised clinical trials. Visual outcomes correlate with treatment intensity at 1 year, with ceiling effects related to baseline VA.

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          Most cited references21

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          Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema.

          The relative efficacy and safety of intravitreous aflibercept, bevacizumab, and ranibizumab in the treatment of diabetic macular edema are unknown.
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            Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE.

            To evaluate the efficacy and safety of intravitreal ranibizumab in diabetic macular edema (DME) patients. Two parallel, methodologically identical, phase III, multicenter, double-masked, sham injection-controlled, randomized studies. Adults with vision loss from DME (best-corrected visual acuity [BCVA], 20/40-20/320 Snellen equivalent) and central subfield thickness ≥275 μm on time-domain optical coherence tomography (OCT). Monthly intravitreal ranibizumab (0.5 or 0.3 mg) or sham injections. Macular laser was available per-protocol-specified criteria. Proportion of patients gaining ≥15 letters in BCVA from baseline at 24 months. In RISE (NCT00473330), 377 patients were randomized (127 to sham, 125 to 0.3 mg, 125 to 0.5 mg). At 24 months, 18.1% of sham patients gained ≥15 letters versus 44.8% of 0.3-mg (P<0.0001; difference vs sham adjusted for randomization stratification factors, 24.3%; 95% confidence interval [CI], 13.8-34.8) and 39.2% of 0.5-mg ranibizumab patients (P<0.001; adjusted difference, 20.9%; 95% CI, 10.7-31.1). In RIDE (NCT00473382), 382 patients were randomized (130 to sham, 125 to 0.3 mg, 127 to 0.5 mg). Significantly more ranibizumab-treated patients gained ≥15 letters: 12.3% of sham patients versus 33.6% of 0.3-mg patients (P<0.0001; adjusted difference, 20.8%; 95% CI, 11.4-30.2) and 45.7% of 0.5-mg ranibizumab patients (P<0.0001; adjusted difference, 33.3%; 95% CI, 23.8-42.8). Significant improvements in macular edema were noted on OCT, and retinopathy was less likely to worsen and more likely to improve in ranibizumab-treated patients. Ranibizumab-treated patients underwent significantly fewer macular laser procedures (mean of 1.8 and 1.6 laser procedures over 24 months in the sham groups vs 0.3-0.8 in ranibizumab groups). Ocular safety was consistent with prior ranibizumab studies; endophthalmitis occurred in 4 ranibizumab patients. The total incidence of deaths from vascular or unknown causes, nonfatal myocardial infarctions, and nonfatal cerebrovascular accidents, which are possible effects from systemic vascular endothelial growth factor inhibition, was 4.9% to 5.5% of sham patients and 2.4% to 8.8% of ranibizumab patients. Ranibizumab rapidly and sustainably improved vision, reduced the risk of further vision loss, and improved macular edema in patients with DME, with low rates of ocular and nonocular harm. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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              Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial.

              To provide 2-year results comparing anti-vascular endothelial growth factor (VEGF) agents for center-involved diabetic macular edema (DME) using a standardized follow-up and retreatment regimen.
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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
                February 2021
                7 April 2020
                : 105
                : 2
                : 216-221
                Affiliations
                [1 ] departmentOphthalmology , Indiana University School of Medicine , Indianapolis, Indiana, USA
                [2 ] departmentRetina Service , Midwest Eye Institute , Indianapolis, Indiana, USA
                [3 ] Rush University , Chicago, Illinois, USA
                [4 ] Illinois Retina Associates , Chicago, IL, USA
                [5 ] University of Minnesota , Minneapolis, Minnesota, USA
                [6 ] VitreoRetinal Surgery, PA , Minneapolis, MN, USA
                Author notes
                [Correspondence to ] Dr Thomas A Ciulla, Indiana University School of Medicine, Indianapolis, Indiana, USA; thomasciulla@ 123456gmail.com
                Author information
                http://orcid.org/0000-0001-5557-6777
                Article
                bjophthalmol-2020-315933
                10.1136/bjophthalmol-2020-315933
                7848066
                32265201
                f831b871-3108-43f7-99a4-3ef304206965
                © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) 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, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 23 January 2020
                : 17 March 2020
                : 19 March 2020
                Categories
                Clinical Science
                1506
                Custom metadata
                unlocked

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

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