Diabetic macular edema (DME)—a manifestation of diabetic retinopathy1—is the leading cause of vision loss in patients with diabetes.2 It is estimated that by 2020, approximately 1.34 million people in the United States will be affected with vision-threatening diabetic retinopathy.3 Risk factors of DME, including the duration of diabetes, severity of hyperglycemia, hypertension, and hyperlipidemia, are now well established,4 and intensive control of blood sugar, blood pressure, and serum lipids is highly encouraged to prevent and reduce some of the complications seen with diabetic retinopathy.4-6 Once it develops, however, strict control of these systemic factors alone is not sufficient to manage DME.7
In 1985, the Early Treatment for Diabetic Retinopathy Study demonstrated that laser photocoagulation achieved a 50% reduction in risk of moderate visual loss in patients with clinically significant macular edema.8 Since then, laser therapy has become the mainstay of therapy for DME.9 However, concerns surrounding some of the damaging effects of laser therapy (including scar expansion,10 choroidal neovascularization,11 subretinal fibrosis,12 and visual field loss13), as well as its inability to achieve significant visual improvement,9 have inspired researchers to find safer, more effective treatment alternatives for DME.9
In recent years, substantial effort has been devoted to investigating pharmacologic agents for DME, including corticosteroids and vascular endothelial growth factor antagonists (anti-VEGFs).2 The use of corticosteroids, such as intravitreal triamcinolone acetonide (IVTA), is now becoming increasingly common in patients whose DME is refractory to laser therapy.14 In addition, the benefit of IVTA adjunct to laser therapy is also being explored; so far, results from different studies have generated conflicting outcomes, where some have shown an added benefit and others have not.15-18 The most common complications of IVTA are cataract formation and increased intraocular pressure.19,20
To reduce the need for repeated intravitreal injections of corticosteroids—as observed with IVTA—extended- and sustained-release corticosteroid devices, including fluocinolone acetonide-eluting intravitreal implants and dexamethasone drug delivery systems, are currently being considered for DME and have yielded encouraging results.21-24
Anti-VEGF therapies are another class of pharmacologic agents investigated for the treatment of DME. There are currently 4 commercially available anti-VEGF agents: pegaptanib, bevacizumab, aflibercept, and ranibizumab4; the latter is the only one approved by the FDA for DME.25 Ranibizumab, a recombinant humanized monoclonal antibody fragment, gained FDA approval in 2012, based on favorable results from 2 randomized, sham-treatment controlled, 3-year studies.25 In addition, outcomes from other studies showed that ranibizumab either alone or in combination with laser therapy, was more effective than laser monotherapy.18,26,27 Clinical trials with bevacizumab, pegaptanib, and aflibercept have similarly yielded more favorable results when compared to sham or laser therapy.28,29 The safety profile of anti-VEGFs reveals that some patients may experience intraocular pressure elevation and only rarely endophthalmitis, following repeated intravitreal injection.30,31
So the question still stands: Will pharmacotherapy eventually replace laser photocoagulation for DME? With current and emerging pharmacologic agents, evidence suggests that treatment may be headed in that direction. Nevertheless, laser therapy continues to play an important part in the treatment of DME, particularly in clinically significant macular edema.32 Furthermore, the role of combination therapies with laser photocoagulation has yet to be clarified.4
- Ciulla TA, Amador AG, Zinman B. Diabetic retinopathy and diabetic macular edema: pathophysiology, screening, and novel therapies. Diabetes Care. 2003;26(9):2653-2664.
- Al Shamsi H, Ghazi NG. Diabetic macular edema: new trends in management. Expert Rev Clin Pharmacol. 2012;5(1):55-68.
- American Academy of Ophthalmology Retina Panel. Preferred Practice Pattern guidelines. Diabetic Retinopathy. San Francisco, CA: American Academy of Ophthalmology; 2008 (4th printing 2012). Available at: http://one.aao.org/CE/PracticeGuidelines/PPP.aspx.
- Javey G, Schwartz SG, Flynn HW Jr. Emerging pharmacotherapies for diabetic macular edema. Exp Diabetes Res. 2012;2012:548732.
- 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.
- UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352(9131):837-853.
- Romero-Aroca P. Managing diabetic macular edema: the leading cause of diabetes blindness. World J Diabetes. 2011;2(6):98-104.
- Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Arch Ophthalmol. 1985;103(12):1796-1806.
- Thomas BJ, Shienbaum G, Boyer DS, Flynn HW Jr. Evolving strategies in the management of diabetic macular edema: clinical trials and current management. Can J Ophthalmol. 2013;48(1):22-30.
- Schatz H, Madeira D, McDonald HR, Johnson RN. Progressive enlargement of laser scars following grid laser photocoagulation for diffuse diabetic macular edema. Arch Ophthalmol. 1991;109(11):1549-1551.
- Lewis H, Schachat AP, Haimann MH, et al. Choroidal neovascularization after laser photocoagulation for diabetic macular edema. Ophthalmology. 1990;97(4):503-510.
- Guyer DR, D’Amico DJ, Smith CW. Subretinal fibrosis after laser photocoagulation for diabetic macular edema. Am J Ophthalmol. 1992;113(6):652-656.
- Striph GG, Hart WM Jr, Olk RJ. Modified grid laser photocoagulation for diabetic macular edema. The effect on the central visual field. Ophthalmology. 1988;95(12):1673-1679.
- Sutter FK, Simpson JM, Gillies MC. Intravitreal triamcinolone for diabetic macular edema that persists after laser treatment: three-month efficacy and safety results of a prospective, randomized, double-masked, placebo-controlled clinical trial. Ophthalmology. 2004;111(11):2044-2049.
- Lam DS, Chan CK, Mohamed S, et al. Intravitreal triamcinolone plus sequential grid laser versus triamcinolone or laser alone for treating diabetic macular edema: six-month outcomes. Ophthalmology. 2007;114(12):2162-2167.
- Avitabile T, Longo A, Reibaldi A. Intravitreal triamcinolone compared with macular laser grid photocoagulation for the treatment of cystoid macular edema. Am J Ophthalmol. 2005;140(4):695-702.
- Kang SW, Sa HS, Cho HY, Kim JI. Macular grid photocoagulation after intravitreal triamcinolone acetonide for diffuse diabetic macular edema. Arch Ophthalmol. 2006;124(5):653-658.
- Diabetic Retinopathy Clinical Research Network, Elman MJ, Aiello LP, Beck RW, et al. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010;117(6):1064-1077.
- Chu YK, Chung EJ, Kwon OW, Lee JH, Koh HJ. Objective evaluation of cataract progression associated with a high dose intravitreal triamcinolone injection. Eye (Lond). 2008;22(7):895-899.
- Smithen LM, Ober MD, Maranan L, Spaide RF. Intravitreal triamcinolone acetonide and intraocular pressure. Am J Ophthalmol. 2004;138(5):740-743.
- Montero JA, Ruiz-Moreno JM. Intravitreal inserts of steroids to treat diabetic macular edema. Curr Diabetes Rev. 2009;5(1):26-32.
- Campochiaro PA, Brown DM, Pearson A, et al; FAME Study Group. Long-term benefit of sustained-delivery fluocinolone acetonide vitreous inserts for diabetic macular edema. Ophthalmology. 2011;118(4):626-635.e2.
- Haller JA, Kuppermann BD, Blumenkranz MS, et al; Dexamethasone DDS Phase II Study Group. Randomized controlled trial of an intravitreous dexamethasone drug delivery system in patients with diabetic macular edema. Arch Ophthalmol. 2010;128(3):289-296.
- Boyer DS, Faber D, Gupta S, et al; Ozurdex CHAMPLAIN Study Group. Dexamethasone intravitreal implant for treatment of diabetic macular edema in vitrectomized patients. Retina. 2011;31(5):915-923.
- Lucentis [ranibizumab injection] [product information]. South San Francisco, CA: Genentech, Inc.; 2013.
- Nguyen QD, Shah SM, Khwaja AA, et al; READ-2 Study Group. Two-year outcomes of the ranibizumab for edema of the mAcula in diabetes (READ-2) study. Ophthalmology. 2010;117(11):2146-2151.
- Mitchell P, Bandello F, Schmidt-Erfurth U, et al; 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.
- Sultan MB, Zhou D, Loftus J, Dombi T, Ice KS; Macugen 1013 Study Group. A phase 2/3, multicenter, randomized, double-masked, 2-year trial of pegaptanib sodium for the treatment of diabetic macular edema. Ophthalmology. 2011;118(6):1107-1118.
- Michaelides M, Kaines A, Hamilton RD, et al. A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: report 2. Ophthalmology. 2010;117(6):1078-1086.e2.
- Good TJ, Kimura AE, Mandava N, Kahook MY. Sustained elevation of intraocular pressure after intravitreal injections of anti-VEGF agents. Br J Ophthalmol. 2011;95(8):1111-1114.
- Moshfeghi AA, Rosenfeld PJ, Flynn HW Jr, et al. Endophthalmitis after intravitreal vascular [corrected] endothelial growth factor antagonists: a six-year experience at a university referral center. Retina. 2011;31(4):662-668.
- American Diabetes Association. Standards of medical care in diabetes)—2013. Diabetes Care. 2013;36 Suppl 1:S11-S66.