Traditionally, the only treatment Retinal specialists have had to offer their patients has been a supplement of antioxidant vitamins and minerals based on the Age-related Eye Disease Study (AREDS). These vitamins have shown a 25% reduction in moderate vision loss in patients with moderate to severe dry macular degeneration associated with drusen. A tremendous amount of research in the field has yielded new approaches to the treatment of this potentially devastating disease: retinal neuroprotection, visual cycle modulation, and complement inhibition.
Retinal neuroprotection is aimed at protecting retinal tissue, and currently three novel drugs are being evaluated. Ciliary neurotrophic factor (CNTF) is a growth factor capable of rescuing dying photoreceptors and protecting them from degeneration. An implant holding cells that produce CNTF can be placed in the eye with a minor surgical procedure. Results from a Phase 2 study showed an increase in retinal tissue thickness as well as improvement in vision in patients with good initial visual acuity. Brimonidine is used in the treatment of glaucoma and has been shown to be protective of certain retinal cells in animal and other experimental models. It has been shown to have a positive effect on the retina in several types of disease states, and is currently being evaluated through an injected drug delivery system. Tandosporine is protective of retinal cells by blocking cell death in times of high stress, and is currently being evaluated in a topical form in a phase 2 trial.
Visual cycle modulation attempts to prevent vision loss by slowing the accumulation of toxic byproducts in the retina. Acucela’s ACU-4429 is an oral medication currently in trial, and thus far has had a good early response. Fenretinide, a derivative of vitamin A, can down-regulate the visual system by binding a transport molecule. In a phase 2 trial, Fenretinide slowed the progression of atrophic macular degeneration and reduced the conversion to wet macular degeneration. This medication is currently moving into a phase 3 trial. It must be mentioned that any medicine that slows the visual cycle can cause trouble with night vision.
The complement cascade is part of the body’s natural immune system, and has been found to be over-activated in some patients with macular degeneration. By slowing down this pathway, destruction of retinal cells may be avoided. Several new agents are being tested in injection form.
Dry macular degeneration is increasing in incidence, and new research is being performed to combat this important public health risk.