Age Related Macular Degeneration

Wet

The wet form of age-related macular degeneration occurs in approximately 15% of patients who have age-related macular degeneration.

Age-related Macular Degeneration

Age-related Macular Degeneration: This is what you see if you have age-related macular degeneration and problems with your central vision.

Patients are now being treated for wet age-related macular degeneration with three drugs: Lucentis, Avastin, and Eylea.

These treatments are used to treat the abnormal blood vessels that occur in the wet form of age-related macular degeneration. However, the type of treatment recommended by physician depends on the location, size, and severity of the abnormal blood vessels.

Treatment for wet age-related macular degeneration is a rapidly changing area, and new information is being gained on a yearly basis as reports of combination therapy or single-treatment therapy with these medications are reported. A new drug called Bevasiranib is being used in patients with wet age-related macular degeneration and diabetic macular edema. It is administered by intravitreal injection. This study is called the RACE study and is in Phase II. The advantage of this new drug is that it may provide patients with a potentially longer duration of effect and require less frequency of injections. Other new medications will undoubtedly become available in the future. We will keep you updated on those as they are reported.

Wet ARMD

Wet ARMD
Right eye has a subretinal neovascular membrane secondary to ARMD. Untreated.

Normal Eye

Normal Eye

Dry

Investigational Therapies For Dry Age-Related Macular Degeneration

The current studies focus on chronic inflammation, the damage of oxidation, and toxins. Researchers are trying to: 1) modulate the normal visual cycle; 2) block the complement system; 3) protect photoreceptors; and 4) introduce nutrients.

1) Visual Cycle Modulator
The human visual cycle uses rods during the night and day and cones during the day. This generates byproducts such as lipofuscin, where the major component is A2E, which accumulates in the RPE and is linked to macular degeneration.

(ACUCELA) ACU-4429, an oral drug that targets rod system. It reduces the rate at which A2E and lipofuscin accumulate in the RPE. A2E triggers inflammation. Phase 2 will begin later in 2009.

Fenretinide (Sirion Therapeutics) is another product that reduces the production of lipofuscin. It is an oral vitamin A binding protein antagonist. It is in Phase II and Phase III should begin in mid-2010.

2) Complement Inhibitor
The complement system is involved in the inflammation process, tissue damage, and increase in angiogenic factors.

POT-4 (Potentia Pharmaceuticals) is designed to inhibit complement component C3, addressing dry age-related macular degeneration and geographic atrophy. Phase 2 studies expect to begin early in 2010 and involve wet and dry patients.

Other work is being done by D. Shima on Complement C5aR inhibitor and by J. Ambati on Toll-like Receptor-3

3) Neuroprotection
Ciliary neurotrophic factor (CNTF) is a neuro-protective cytokine.

NT-501 intraocular implant (Neurotech) secretes CNTF. Phase 2 trials reported by Neurotech showed it substantially slowed the loss of vision in patients with geographic atrophy.

OT-551 (Othera Pharmaceuticals) is a typical drop used to treat geographic atrophy. Early studies revealed patient discomfort with the drop. A phase 2 study OMEGA is underway. The chairman of the OMEGA committee is Paul Sternberg, Sr., M.D. at Vanderbilt. This agent may protect retinal pigment epithelium (RPE) cells and photoreceptors from oxidative damage and angiogenesis stimulated by vascular endothelial growth factor (VEGF)

4) Carotenoid Supplementation
The AREDS trial found that certain nutrients are protective against dry age-related macular degeneration.

Now, the AREDS formula is being modified by elementary beta-carotene, decreasing the zinc, and adding omega-3 fatty acids and two xanthophylls, lutein, and zeaxanthin. Dr. Bernstein found that lutein works as an antioxidant while zeaxanthin acts as a light-screening compound.

Definitive AREDS 2 recommendations are 4 to 5 years off, but taking additional supplements of lutein and zeaxanthin has little downside.

Risk Factors

Age
Age is an important factor in developing age-related macular degeneration. Anyone over the age of 55 is at risk and the percentage increases with increasing age.

Smoking
Smoking effects all tissues in the body and the retina is no exception. It is thought that is can increase the chance of developing age-related macular degeneration by 30%.

Genetics
Family history plays a role in increasing the risk of developing age-related macular degeneration. More genes are being discovered every year that are related to causing this disease.

Race
Caucasians are more susceptible to developing age-related macular degeneration that any other race.

Diet
Eating foods with high fat, cholesterol, and glucose and low intake of leafy green vegetables are more likely to be affected with age-related macular degeneration.

Obesity
Overweight individuals are at increased risk for developing age-related macular degeneration. Some studies correlate this with increasing body mass index.

High Blood Pressure
The effects of high blood pressure on the vessels of the retina lead to decreased blood flow and poor circulation of the retina. This adversely affects the health of the macular area.

Presence of Macular Degeneration in One Eye
If an individual has wet age-related macular degeneration in one eye and dry in the other eye, they are at a 25% risk of developing wet age-related macular degeneration in the second eye within two years.