From Laser to Pharmacotherapy: Is Laser Therapy for Diabetic Macular Edema Becoming a Thing of the Past?
Lilly Ostrovsky, MS

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


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