Wet Age-Related Macular Degeneration (AMD) and Diabetic Macular Edema (DME)
AMD is the leading cause of irreversible vision loss in industrialized nations for those ages 65 and above. Most patients with severe visual loss suffer from the wet form of AMD wherein there is choroidal neovascularization (CNV) and associated manifestations such as retinal pigment epithelial detachment, subretinal hemorrhages, and fibrovascular disciform scarring. Currently, three types of treatments have been demonstrated to limit or delay loss of vision in patients: laser photocoagulation, photodynamic therapy and anti-VEGF intravitreal injections. However, given the progressive nature of wet AMD and the need for repeated therapy for the balance of a patient’s life, only a small portion of cases can sustain the initial improvement in vision seen with these therapies. This highlights the unmet need for better pharmacologic interventions, with the goal of lowering recurrence rates and preventing the development of CNV to achieve better functional outcomes.
DME is characterized by the breakdown of the blood vessel walls in the retina resulting in the accumulation of fluid and proteins in the retina. This leads to distortion of the macula and visual impairment or loss of visual acuity. Local hypoxia triggers intraocular proliferation of retinal blood vessels and contributes to the subsequent loss of vision.
DME is a highly prevalent cause of vision loss worldwide. Among an estimated 422 million individuals living with diabetes (Types 1 and 2) globally, prevalence rates for diabetic macular edema are 6.8%. This translates to 28 million individuals with DME, the largest cause of new cases of visual loss in individuals aged 20 to 74 years old.
Current treatment options
The standard of care for wet AMD and DME is frequent, monthly or every other month, injections of drugs into the eye that target vascular endothelial growth factor or VEGF. Intravitreal injections of anti-VEGF agents such as Lucentis (ranibizumab) or Eylea (aflibercept) are effective at reducing retinal thickness; however, the fluid and swelling may recur with discontinued therapy. These anti-VEGF therapies rarely provide a cure of the underlying disease.
There are several additional therapies that have been used to treat DME including corticosteroids such as triamcinolone, fluocinolone and dexamethasone, which are all administered via injections into the eye. Novel sustained release corticosteroids such as Illuvien (fluocinolone) and Ozurdex (dexamethasone), have recently been approved for use in DME, which reduce the number of injections required to obtain and maintain clinical responses. Corticosteroid treatment, however, is associated with a significant increase in cataract formation and a rise in intraocular pressure, eliminating these agents as potential therapies in many patients.
The typical response in wet AMD and DME from anti-VEGF therapy is that 30-40% of patients improve their visual acuity by 15 letters or more, referring to the number of letters, arranged in lines that the patient can read on the ETDRS eye chart. This leaves a significant portion of the patients with inadequate control of their disease.