Recommendations for the Appropriate Management of Diabetic Macular Edema: Light on DME Survey and Consensus Document by an Expert Panel

Abstract

Purpose

The Light on DME survey was designed to address several issues concerning the management of diabetic macular edema (DME) with the objective of producing practical recommendations for the appropriate treatment of this condition.

Methods

The recommendations considered aspects of DME treatment that are controversial and insufficiently supported by the evidence and were based on a consensus reached by an expert panel. Consensus was achieved by means of the Delphi method. Thirty-one Italian retinologists were asked to rate the appropriateness of a comprehensive set of scenarios typically encountered in the management of DME in clinical practice. The results of the appropriateness evaluation were analyzed by the study panel and a second assessment round was conducted for those scenarios on which no consensus was reached.

Results

Consensus was reached on several relevant aspects of current DME management, namely the initiation and course of treatment with anti-vascular endothelial growth factor (VEGF) therapy, assessment of the outcomes of anti-VEGF therapy based on both functional and morphologic outcomes, combination of anti-VEGF with laser therapy, and management of nonresponders to anti-VEGFs. A few issues, including the definition of DME based on novel diagnostic tools, the need for stable metabolic parameters before initiating anti-VEGF therapy, and the use of a second anti-VEFG after failure of the first anti-VEGF, proved controversial.

Conclusions

A clear consensus among DME experts was reached on several relevant aspects of DME management. Based on this consensus, detailed and practical recommendations to guide ophthalmologists in the use of novel approaches to DME could be developed.

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References

Cheung

Mitchell

Wong

Diabetic retinopathy. Lancet 2010; 376(9735): 124–136.

Yau

JWY

Rogers

Kawasaki

; Meta-Analysis for Eye Disease (META-EYE) Study Group. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 2012; 35(3): 556–564.

Klein

Knudtson

Lee

Gangnon

Klein

The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XXII: the twenty-five-year progression of retinopathy in persons with type 1 diabetes. Ophthalmology 2008; 115(11): 1859–1868.

Klein

Knudtson

Lee

Gangnon

Klein

The Wisconsin Epidemiologic Study of Diabetic Retinopathy XXIII: the twenty-five-year incidence of macular edema in persons with type 1 diabetes. Ophthalmology 2009; 116(3): 497–503.

Moss

Klein

Ten-year incidence of visual loss in a diabetic population. Ophthalmology 1994; 101(6): 1061–1070.

Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Arch Ophthalmol 19851031796–1805.

Early Treatment Diabetic Retinopathy Study Research Group. Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema. Early Treatment Diabetic Retinopathy Study Report Number 2. Ophthalmology 1987; 94(7): 761–774.

The Royal College of Ophthalmologists. Diabetic Retinopathy Guidelines 2012 Available at: http://www.icoph.org/dynamic/attachments/taskforce_documents/2012-sci-267_diabetic_retinopathy_guidelines_december_2012.pdf Accessed March 5, 2015.

Mitchell

Bandello

Schmidt-Erfurth

; RESTORE study group. The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology 2011; 118(4): 615–625.

10.

Dowler

Laser management of diabetic retinopathy. J R Soc Med 2003; 96(6): 277–279.

11.

Aiello

Avery

Arrigg

Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994; 331(22): 1480–1487.

12.

Bandello

Cunha-Vaz

Chong

New approaches for the treatment of diabetic macular oedema: recommendations by an expert panel. Eye 2012; 26(4): 485–493.

13.

Bandello

Casalino

Loewenstein

Goldstein

Pelayes

Battaglia Parodi

Pharmacological approach to diabetic macular edema. Ophthalmic Res 2014; 51(2): 88–95.

14.

Stewart

Anti-VEGF therapy for diabetic macular edema. Curr Diab Rep 2014; 14(8): 510.

15.

Massin

Bandello

Garweg

Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE Study): a 12-month, randomized, controlled, double-masked, multicenter phase II study. Diabetes Care 2010; 33(11): 2399–2405.

16.

Nguyen

Shah

Khwaja

; READ-2 Study Group. Two-year outcomes of the Ranibizumab for Edema of the Macula in Diabetes (READ-2) study [erratum 2011;118:1016]. Ophthalmology 2010; 117(11): 2146–2151.

17.

Elman

Bressler

Qin

; Diabetic Retinopathy Clinical Research Network. Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 2011; 118(4): 609–614.

18.

Elman

Qin

Aiello

; Diabetic Retinopathy Clinical Research Network. Intravitreal ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: three-year randomized trial results. Ophthalmology 2012; 119(11): 2312–2318.

19.

Nguyen

Brown

Marcus

; RISE and RIDE Research Group. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology 2012; 119(4): 789–801.

20.

Nguyen

Khwaja

; READ-2 Study Group. Ranibizumab for edema of the macula in diabetes study: 3-year outcomes and the need for prolonged frequent treatment. JAMA Ophthalmol 2013; 131(2): 139–145.

21.

Mitchell

Bressler

Tolley

; RESTORE Study Group. Patient-reported visual function outcomes improve after ranibizumab treatment in patients with vision impairment due to diabetic macular edema: randomized clinical trial. JAMA Ophthalmol 2013; 131(10): 1339–1347.

22.

Schmidt-Erfurth

Lang

Holz

; RESTORE Extension Study Group. Three-year outcomes of individualized ranibizumab treatment in patients with diabetic macular edema: the RESTORE extension study. Ophthalmology 2014; 121(5): 1045–1053.

23.

Brown

Nguyen

Marcus

; RIDE and RISE Research Group. Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE. Ophthalmology 2013; 120(10): 2013–2022.

24.

Wilson

JGM

Jungner

Principles and Practice of Screening for Disease. Geneva: World Health Organization, 1968 Available at: http://apps.who.int/iris/handle/10665/37650. Accessed December 26, 2015.

25.

Echouffo-Tcheugui

Ali

Roglic

Hayward

Narayan

Screening intervals for diabetic retinopathy and incidence of visual loss: a systematic review. Diabet Med 2013; 30(11): 1272–1292.

26.

Bäcklund

Algvere

Rosenqvist

New blindness in diabetes reduced by more than one-third in Stockholm County. Diabet Med 1997; 14(9): 732–740.

27.

Arun

Al-Bermani

Stannard

Taylor

Long-term impact of retinal screening on significant diabetes-related visual impairment in the working age population. Diabet Med 2009; 26(5): 489–492.

28.

Arora

Kolb

Goyder

McKibbin

Trends in the incidence of visual impairment resulting from diabetic retinopathy in the Leeds metropolitan area, 2005-2010. Diabet Med 2012; 29(7): e112–e116.

29.

Hautala

Aikkila

Korpelainen

Marked reductions in visual impairment due to diabetic retinopathy achieved by efficient screening and timely treatment. Acta Ophthalmol 2014; 92(6): 582–587.

30.

Bressler

Varma

Doan

Underuse of the health care system by persons with diabetes mellitus and diabetic macular edema in the United States. JAMA Ophthalmol 2014; 132(2): 168–173.

31.

Trento

Bajardi

Borgo

Perceptions of diabetic retinopathy and screening procedures among diabetic people. Diabet Med 2002; 19(10): 810–813.

32.

Linee-guida per lo screening, la diagnostica e il trattamento della retinopatia diabetica in Italia. Revisione e aggiornamento 2013 a cura del Gruppo di Lavoro sulle Complicanze Oculari del Diabete della Società Italiana di Diabetologia Available at: http://www.aemmedi.it/files/Linee-guida_Raccomandazioni/2002/2002-screening-diagnostica-trattamento-retinopatia-diabetica.pdf. Accessed June 4, 2015.

33.

Panozzo

Parolini

Gusson

Diabetic macular edema: an OCT-based classification. Semin Ophthalmol 2004; 19(1-2): 13–20.

34.

Want

Rewbury

Varughese

Chong

Classification of diabetic macular edema based on the morphology in optical coherent topography. Poster presented at the annual meeting of the Association for Research in Vision and Ophthalmology; Orlando, FL, USA; May 4-8, 2014. Available at: http://www.arvo.org/webs/am2014/abstract/sessions/345.pdf. Accessed June 4, 2015.

35.

The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329(14): 977–986.

36.

The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. N Engl J Med 2000; 342(6): 381–389.

37.

Kiire

Porta

Chong

Medical management for the prevention and treatment of diabetic macular edema. Surv Ophthalmol 2013; 58(5): 459–465.

38.

Matsuda

Tam

Singh

The impact of metabolic parameters on clinical response to VEGF inhibitors for diabetic macular edema. J Diabetes Complications 2014; 28(2): 166–170.

39.

Ranibizumab for treating diabetic macular oedema. NICE technology appraisal guidance 274. April 2013 Available at: https://www.nice.org.uk/guidance/ta274. Accessed December 26, 2015.

40.

Lucentis® (ranibizumab) Summary of Product Characteristics. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_Product_Information/human/000715/WC500043546.pdf. Accessed June 4, 2015.

41.

Pruente

Group

Efficacy and safety of ranibizumab in two treat-and-extend versus pro-re-nata regimes in patients with visual impairment due to diabetic macular edema: 24-month results of RETAIN study. Invest Ophthalmol Vis Sci 201455 E-Abstract 1700.

42.

Zehetner

Kirchmair

Huber

Kralinger

Kieselbach

Plasma levels of vascular endothelial growth factor before and after intravitreal injection of bevacizumab, ranibizumab and pegaptanib in patients with age-related macular degeneration, and in patients with diabetic macular oedema. Br J Ophthalmol 2013; 97(4): 454–459.

43.

Wells

Glassman

Ayala

; Diabetic Retinopathy Clinical Research Network. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med 2015; 372(13): 1193–1203.