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Large study of combination therapy for DME needed

Anti-VEGF therapy with corticosteroids and laser photocoagulation may be the most effective treatment for diabetic macular edema.

ByTimothy Y.Y. Lai, MD, MBBS, FRCSEd, FRCOphth

ByDennis S.C. Lam, MD, FRCOphth

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Dennis S.C. Lam

Diabetic macular edema is one of the most sight-threatening complications in diabetes mellitus. DME has been estimated to occur in around 10% of the diabetic population, with a prevalence as high as 30% in patients with more than a 25-year history of diabetes. Until the last 5 to 10 years, based on the results of the Early Treatment Diabetic Retinopathy Study, grid or focal laser photocoagulation treatment to the macula has been the standard of care in the treatment of DME. However, the long-term results of grid laser photocoagulation have been suboptimal, as only 15% of patients developed visual improvement 3 years after treatment.

In 2001, the first case report in the use of intravitreal triamcinolone acetonide (IVTA) injection for DME refractory to grid laser photocoagulation was published. This innovative treatment modality provided exciting new hope for the entire ophthalmic community. Unfortunately, despite the early success in reducing macular thickness and in improving visual acuity, recurrence of DME after IVTA was not uncommon. Moreover, side effects including ocular hypertension and cataract formation, especially on repeat IVTA injection, are common and could be serious. Therefore, IVTA was still not the ideal treatment for DME.

One of the reasons for the limited benefit of grid laser photocoagulation in DME was the breakdown of the inner blood-retinal barrier with release of endogenous permeability factors by the ischemic retina, such as vascular endothelial growth factors (VEGF). Pharmacological agents that inhibit the production or action of VEGF might thus be useful in treating DME by reducing the amount of vascular hyperpermeability. Several anti-VEGF agents including pegaptanib and bevacizumab have been used intraocularly in order to inhibit VEGF for DME treatment. Clinical trials have demonstrated that anti-VEGF agents might be useful in improving vision and in reducing retinal thickness in patients with DME. However, the treatment responses to anti-VEGF monotherapy were quite variable and the anatomical reduction in macular thickness appeared to be less compared with IVTA.

Therefore, despite the availability of IVTA and anti-VEGF agents as new treatment modalities for DME in recent years, the final verdict for the optimal treatment for DME is still very much open. There is preliminary evidence that combination therapy to target different pathways in the pathogenesis of DME with anti-VEGF, corticosteroid and macular laser photocoagulation might have the ability to set a new benchmark for treating DME. Large-scale, prospective, multicenter, randomized, controlled clinical trials for evaluating the role of combination therapy in DME are urgently needed.

For more information:

• Dennis S.C. Lam, MD, FRCS, FRCOphth, and Timothy Y.Y. Lai, MD, FCOphth, can be reached at Chinese Univ. of Hong Kong/Hong Kong Eye Hospital, University Eye Centre; 3/F, 147K Argyle St., Kowloon, Hong Kong SAR, China.

References:

• Gaudric A, Massin-Korobelnik P. Diabetic maculopathy: classification, epidemiology, spontaneous outcome, treatment. Diabete Metab. 1993;19:422-9.
• Haritoglou C, Kook D, Neubauer A, et al. Intravitreal bevacizumab (Avastin) therapy for persistent diffuse diabetic macular edema. Retina. 2006;26:999-1005.
• Jonas JB, Söfker A. Intraocular injection of crystalline cortisone as adjunctive treatment of diabetic macular edema. Am J Ophthalmol. 2001;132:425-427.
• Lam DS, Chan CK, Mohamed S, Lai TY, Lee VY, Liu DT, Li KK, Li PS, Shanmugam MP. Intravitreal triamcinolone plus sequential grid laser versus triamcinolone or laser alone for treating diabetic macular edema: six-month outcomes. Ophthalmology. 2007;114:2162-2167.
• Lee CM, Olk RJ. Modified grid laser photocoagulation for diffuse diabetic macular edema. Long-term visual results. Ophthalmology. 1991;98:1594-1602.