As aforementioned, VEGF causes increased vascular permeability and breakdown of the blood-retinal barrier. Patients with DME have been shown to have increased levels of VEGF in the vitreous when compared with nondiabetic controls. 21 There are now 3 anti-VEGF agents that are commonly used in clinical practice for the treatment of DME: ranibizumab, aflibercept, and bevacizumab. Ranibizumab is an antibody fragment targeted against VEGF that is FDA approved for use in patients with DME. The Diabetic Retinopathy Clinical Research Network Protocol I showed that treatment with ranibizumab, paired with deferred laser treatment, results in greater visual improvement than does prompt laser treatment alone. 22 Treatment with aflibercept is a recombinant fusion protein of VEGF receptors. It was shown to be superior in terms of visual improvement when compared with laser treatment. 23 Bevacizumab is a full-length antibody that is more affordable than other anti-VEGF medications and is often used off label for the treatment of DME. All of the anti-VEGF therapies are intravitreal injections. After topical anesthesia, the medication is injected through the sclera into the vitreous cavity in the outpatient clinic setting.
A significant disadvantage of the anti-VEGF therapies is that many patients need monthly injections, especially in the first year of treatment, necessitating many office visits, which can decrease adherence. In some patients, the edema may not respond to anti-VEGF therapy. In these cases, steroid therapy may be helpful to suppress the inflammatory pathways that are independent of VEGF. Intravitreal triamcinolone in combination with laser treatment has been shown to be as effective as ranibizumab in a small group of patients. 24 An intravitreal dexamethasone implant, which has a treatment effect lasting for 3 months, was also shown to improve visual acuity over sham treatment in patients with DME. 25 Most recently, an intravitreal fluocinolone implant that lasts 3 years was approved by the FDA for treatment of DME. 26 A significant benefit of the steroid implants is the long duration of treatment effect compared with that of the anti-VEGF injections. However, steroid therapy is associated with the development of cataracts and glaucoma, the rates of which are increased when treatment is prolonged. Because of these adverse effects, steroids are currently used as second-line or third-line treatment in DME. Retinal surgery may be indicated if there is vitreomacular traction that is exacerbating the DME. A vitrectomy is performed to remove the vitreous and relieve any adhesion to the surface of the retina.
Conclusion
Despite the new ophthalmic treatment modalities, it is important to remember that DME is a chronic condition that will require long-term follow-up. Many patients will not experience complete resolution of DME with a single therapy alone. Control of systemic risk factors, including blood sugar with a goal of A 1c < 7%, blood pressure, and cholesterol, remains the key to a successful treatment program. Primary care physicians, endocrinologists, diabetologists, optometrists, comprehensive ophthalmologists, retina specialists, and patients must work together to create an individualized treatment regimen that will optimize the patient’s vision by preventing blindness and improving his/her quality of life for years to come.