Diabetic Macular Edema: Changing Treatment Paradigms

J. Fernando Arevalo


Curr Opin Ophthalmol. 2014;25(6):502-507. 

In This Article

Laser Treatment, Sustained-release Implants, and Combination Therapy for Diabetic Macular Edema

Focal/grid photocoagulation was the standard treatment for DME until the recent advent of anti-VEGF therapy. Intravitreal ranibizumab therapy with prompt or deferred (≥24 weeks) focal/grid laser treatment has been demonstrated to result in superior visual acuity outcomes compared with sham injection plus focal/grid laser treatment, as have bevacizumab and aflibercept in smaller randomized clinical trials.[8–9,20–21] However, new treatment paradigms are likely to continue to use photocoagulation in some circumstances.

Bressler et al.[22] evaluated data from two randomized clinical trials for differences in visual acuity and OCT parameters for eyes assigned to sham injection + prompt laser, ranibizumab + prompt laser, or prompt laser only: among subgroups of eyes treated exclusively and electively with either green or yellow laser. When comparing wavelength groups meaningful differences were not detected at 1 year or 2 years.

Inflammation has an important role in the pathogenesis of DME. The breakdown of the blood–retinal barrier involves the recruitment and adhesion of leukocytes to the retinal vascular endothelium (leukostasis), expression of inflammatory factors. Corticosteroids may be useful in the treatment of DME because they block leukostasis; inhibit the expression of prostaglandins, proinflammatory cytokines, and VEGF; and enhance the barrier function of vascular tight junctions.

Callanan et al.[23] conducted a randomized, controlled, multicenter, double-masked, parallel-group, 12-month trial to evaluate the dexamethasone sustained-release intravitreal implant (DEX implant, Ozurdex, Allergan, Inc., Irvine, California, USA) 0.7 mg combined with laser photocoagulation compared with laser alone for treatment of diffuse DME. In patients with angiographically verified diffuse DME, the mean improvement in BCVA was significantly greater with DEX implant plus laser treatment than with laser treatment alone (up to 7.9 vs. 2.3 letters) at all time points through month 9 (P ≤ 0.013). Decreases in the area of diffuse vascular leakage measured angiographically were significantly larger with DEX implant plus laser treatment through month 12 (P ≤ 0.041). Increased intraocular pressure was more common with combination treatment. The authors concluded that there was no significant between-group difference at month 12. However, significantly greater improvement in BCVA, as demonstrated by changes from baseline at various time points up to 9 months and across time based on the area under the curve analysis, occurred in patients with diffuse DME treated with DEX implant plus laser than in patients treated with laser alone.

In summary, the results of this study have demonstrated that sustained-release drug delivery with DEX implant in combination with laser therapy reduces vascular leakage and retinal edema and improves visual acuity more than laser therapy alone in patients with diffuse DME confirmed on angiography, although the difference was not statistically significant at month 12. Additional studies with re-treatment earlier than 6 months are warranted.