Today, more than 26 million Americans have either type 1 or type 2 diabetes.1 The most common microvascular complication of diabetes is probably diabetic retinopathy (DR). Diabetic macular edema (DME) is the leading cause of visual impairment in American adults; however, severe vision loss is preventable if the condition is diagnosed and treated early.1,2
DME is a multifactorial disease that results in increased vascular permeability and causes a breakdown of the blood-retinal barrier. Treatment goals for DME include reducing retinal thickness, increasing visual acuity and minimizing the risk for potentially adverse side effects.
Unfortunately, conventional treatment options, such as laser photocoagulation, are still associated with significant postoperative challenges. However, improved understanding about the pathogenesis of the disease during the last decade has yielded research into more effective treatment options, such as steroid injections and anti-vascular endothelium growth factor (VEGF) therapy (see
New Steroid Insert for DME, May 2009).
Standard Treatment Options
Today, focal/grid laser photocoagulation remains the mainstream treatment for patients with DME. In the mid-1980s, the authors of the Early Treatment Diabetic Retinopathy Study (ETDRS) endorsed laser photocoagulation as the primary treatment for DME, suggesting
that it decreased the risk of moderate vision loss by 50% in comparison to patients who did not receive any treatment.3,4
Although laser photocoagulation halts the progression of DME and is associated with decreased retinal thickness, the procedure does not routinely yield visual acuity gain.4 Though focal DME has proven to react better to laser photocoagulation than diffuse DME, more than 10% of patients who undergo the procedure still experience moderate vision loss.3,4 Also, laser is not effective in all cases of DME, including diffuse macular edema and refractory edema. And, many patients experience complications following laser treatment, including scotoma and epiretinal membrane formation.3,4
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Anti-vascular endothelium growth factor (VEGF) therapy might be an effective
treatment option for patients with diabetic macular edema (DMA), as seen here. |
Novel Treatment Options
A hypoxic environment results from alterations in the normal
vascular structure caused by DME. Hypoxia, in turn, leads to increased levels of VEGF, which further
contributes to increased inflammation and permeability. This complex cascade leads to extracellular leakage, which eventually manifests as macular edema.
VEGF has been shown to play a critical role in the development of macular edema, and high levels of VEGF have been found in the aqueous humor of patients with DME.5,6 So, anti-VEGF treatment may target the underlying pathogenesis associated with the development of DME.
Anti-VEGF therapy is already used for inhibiting angiogenesis in other disease processes, such as wet age-related macular degeneration. Anti-VEGF treatment not only plays a role in inhibiting angiogenesis, but also it is associated with cessation of permeability.
Two decades after the ETDRS results were published, investigators began administering off-label injections of anti-VEGF agents for the treatment of DME. This set the stage for several randomized clinical trials designed to evaluate the efficacy and safety of anti-VEGF therapy in the treatment of DME.7,8 These trials have demonstrated decreased retinal thickness, improved visual acuity and enhanced safety parameters when using Lucentis (ranibizumab, Genentech) to treat patients with DME.
Additionally, J. Fernando Arevalo, M.D., and associates showed a decrease in retinal thickness and improvement of visual acuity in patients with DME following intravitreal injections of Avastin (bevacizumab, Genentech).9 More than half of the patients in Dr. Arevalos study showed two or more lines of visual improvement, and 40% showed
stability of vision at six-month follow-up.9 Several other studies have confirmed the benefits of intravitreal Avastin as a primary treatment for DME.10,11
Compelling research-based evidence supports the use of anti-VEGF therapy for the treatment of DME; however, the number of documented studies is limited. Fortunately, current large-scale studies should help improve future treatments for DME. But, as always, additional research will be required to confirm both their safety and efficacy.
1. The Centers for Disease Control and Prevention. National diabetes fact sheet: general information and national estimates on diabetes in the United States, 2007. Available at:
www.cdc.gov/diabetes/pubs/pdf/ndfs_2007.pdf (accessed June 5, 2009).
2. Klein R, Klein BE, Moss SE, Cruickshanks KJ. The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XVII. The 14-year incidence and progression of diabetic retinopathy and associated risk factors in type 1 diabetes. Ophthalmology 1998 Oct;105(10): 1801-15.
3. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol 1985 Dec;103(12):1796-806.
4. Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 1991 May;98(5 Suppl):766-85.
5. Funatsu H, Yamashita H, Sakata K, et al. Vitreous levels of vascular endothelial growth factor and intercellular adhesion molecule 1 are related to diabetic macular edema. Ophthalmology 2005 May;112(5):806-16.
6. Aiello LP, Avery RL. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994 Dec 1;331(22):1480-7.
7. Nguyen QD. The READ-2 Study: Ranibizumab for edema of the macula in diabetes. Clinical Trial ID: NCT00407381. Available at:
http://clinicaltrials.gov/show/NCT00407381 (accessed June 5, 2009).
8. Novartis Pharmaceuticals. RESOLVE: Safety and efficacy of ranibizumab in diabetic macular edema with center involvement. Clinical Trial ID: NCT00284050. Available at:
http://clinicaltrials.gov/ct2/show/NCT00284050 (accessed June 5, 2009).
9. Arevalo JF, Fromow-Guerra J, Quiroz-Mercado H, et al. Primary intravitreal bevacizumab (Avastin) for diabetic macular edema: results from the Pan-American Collaborative Retina Study Group at 6-month follow-up. Ophthalmology 2007 Apr; 114(4):743-50.
10. Scott IU, Edwards AR, Beck RW, et al. A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema. Ophthalmology 2007 Oct;114(10):1860-7.
11. Soheilian M, Ramezani A, Bijanzadeh B, et al. Intravitreal bevacizumab (Avastin) injection alone or combined with triamcinolone versus macular photocoagulation as primary treatment of diabetic macular edema. Retina 2007 Nov-Dec;27(9):1187-95.