The Leading Cause of Blindness for People Over 50

Dry Age-Related Macular Degeneration (dry-AMD) is the number one cause of unpreventable blindness in the world. In the United States, more patients turn blind due to AMD than due to glaucoma and cataract combined. As dry-AMD is a chronic disease of aging, the number of people affected by AMD is expected to dramatically increase over the next few years. Because of the absence of treatment, the disease is however not as well known as Parkinson's or Alzheimer's diseases, despite the fact that there are more patients affected by dry-AMD than patients suffering from by Parkinson's, Alzheimer's, breast cancer and prostate cancer combined. The disease mostly affects people over 50 years of age and there is currently no FDA approved drug for dry-AMD.

There are two forms of AMD: dry-AMD and wet-AMD. If both forms may eventually lead to partial or complete blindness, these two diseases are different in nature:

  • Dry-AMD is a degenerative disease, where the photoreceptors located at the back of the eye (the retina) degenerate. Dry-AMD accounts for about 90% of all cases of AMD, although not all people experience visual symptoms, particularly in the early stages of the disease.
  • Wet-AMD is characterized by blood vessel formation and bleeding in the back of the eye (the retina), resulting in rapid loss of vision. Wet-AMD accounts for 10% of the cases and is typically treated with the drug Lucentis (or Avastin off-label).

Despite high prevalence, dry-AMD remains untreated due to historically poor understanding of the disease, which slowed the discovery of novel medicines. Recent data has helped elucidate the origins of dry-AMD and how it subsequently progresses. Most of this information was acquired during long term clinical studies (the AREDS studies) sponsored by the National Eye Institute (NEI).

The data generated by AREDS also helped demonstrate that a specific blend of vitamins and antioxidants (available over the counter) could at least slow the rate of progression of AMD. Although this discovery was encouraging, an actual pharmaceutical treatment is still needed to potentially completely stop the progression of vision loss in dry-AMD. Such a treatment would benefit millions of patients worldwide.

Although one would hope for a drug that can treat all patients equally, medicines that are designed to prevent progression are different than those aimed at regenerating dead tissue. For example, a drug that stops the disease progression, also called a "disease-modifying drug" would most likely benefit those patients with minimal vision loss, whereas a treatment that could help restore some of the lost vision would benefit patients with more advanced vision loss. Clinicians grade AMD in approximately 3 stages:

  • Early-stage AMD is usually the stage at which patients are first diagnosed. At this stage, most patients have no serious visual disturbance and some patients may have some mild signs of visual discomfort or slightly blurred vision. There are over 10 million people diagnosed with early-AMD in the US. Fortunately, the majority of patients will remain at this early stage and never progress to the more serious forms. Besides, it may take 5 to 10 years before progressing to the intermediate stage of AMD.
  • Intermediate AMD is manifested by small 'gaps or holes' in patients' vision, problems distinguishing colors, poor night vision, wavy lines instead of straight lines. Patients may start losing some of their central vision while their peripheral vision remains relatively good. Loss of central vision means poor ability to read, write, drive, recognize faces. Usually one eye will degenerate slightly faster than the other eye, although the other eye is likely to follow. The severity of this intermediate form is graded by a specialized physician from grade 1 to grade 4 during a routine eye exam. Grade 3 and grade 4 are the most severe forms of intermediate AMD and have the highest probability of progressing to the late form of the disease (see figure below). Intermediate-AMD often progresses slightly faster than early-AMD. About 8 million people live with intermediate AMD in the USA.
  • Late-stage AMD is the most serious form of the disease. It can take the form of wet, dry, or a combination of both. The late form of dry-AMD, also called geographic atrophy, is often characterized by incapacitated vision and legal blindness. About 1 million patients in the USA live with the late form of dry-AMD, a number expected to double by 2020 due to the aging population. These patients have often limited ability to read, write, watch a movie, see at night, recognize faces, drive and be independent.

Once diagnosed by a retinal specialist, patients with AMD are monitored annually (ore more often if diagnosed with wet-AMD). The lack of treatment option for dry-AMD makes patients more likely to feel depressed and scientists and physicians are eager to develop new treatments.

Alkeus Pharma is developing novel medicines to slow or stop the progression of dry-AMD.