New Research: Two Potential Treatments for Dry Macular Degeneration and Geographic Atrophy

a retinal photograph of dry AMD
A retina with dry AMD

One of the most significant challenges facing eye and vision researchers is developing an effective treatment for dry age-related macular degeneration (AMD). Although there are a number of well-regarded FDA-approved drug treatments for wet AMD, the key to effective dry AMD treatment continues to be elusive.

Current treatments for dry AMD include a number of non-drug-related measures, including (a) nutritional supplements recommended by the Age-Related Eye Disease Study 2 (AREDS2), and (b) controlling a range of lifestyle factors, including diet, weight, blood pressure, smoking, and blue and ultraviolet light exposure.

Although a cure is not yet in sight, two early-stage clinical trials (both explained below) may show future promise as potential treatments for dry AMD:

Please note: Even though this research has produced interesting results, both projects are in their very earliest stages and must be subjected to additional, longer-term, rigorous study and clinical trials, encompassing many more years of research.

What Is Age-Related Macular Degeneration?

NEI image of how someone with macular degeneration sees: overall blurriness with a blind spot in the center
Seeing the world with AMD

Age-related macular degeneration (AMD) is a gradual, progressive, painless deterioration of the macula, the small sensitive area in the center of the retina that provides clear central vision. Damage to the macula impairs the central (or “detail”) vision that helps with essential everyday activities, such as reading, preparing meals, watching television, playing card and board games, and sewing.

AMD is the leading cause of vision loss for people aged 60 and older in the United States. According to the American Academy of Ophthalmology, 10-15 million people have AMD and about 10% of people who are affected have the “wet” type of AMD.

About Dry Macular Degeneration

The dry (also called atrophic) type of AMD affects approximately 80-90% of individuals with AMD. Its cause is unknown, it tends to progress more slowly than the wet type, and there is not – as of yet – an approved treatment or cure. “Atrophy” refers to the degeneration of cells in a portion of the body; in this case, the cell degeneration occurs in the retina.

In dry age-related macular degeneration, small white or yellowish deposits, called drusen, form on the retina, in the macula, causing it to deteriorate or degenerate over time.

Photograph of a retina with drusen

A retina with drusen

Drusen are the hallmark of dry AMD. These small yellow deposits beneath the retina are a buildup of waste materials, composed of cholesterol, protein, and fats. Typically, when drusen first form, they do not cause vision loss. However, they are a risk factor for progressing to vision loss.

Wet (Neovascular) Macular Degeneration

In wet, or exudative, macular degeneration (AMD), the choroid (a part of the eye containing blood vessels that nourish the retina) begins to sprout abnormal new blood vessels that develop into a cluster under the macula, called choroidal neovascularization (neo = new; vascular = blood vessels).

Because these new blood vessels are abnormal, they tend to break, bleed, and leak fluid under the macula, causing it to lift up and pull away from its base. This damages the fragile photoreceptor cells, which sense and receive light, resulting in a rapid and severe loss of central vision.

Two Clinical Trials for Dry AMD and Geographic Atrophy

Two current clinical trials focus on geographic atrophy (GA), which is the most severe and advanced form of dry AMD. GA involves patches of cells in the retina that have degenerated or died off:

  • Atrophy refers to the degeneration of the deepest cells of the retina, called the retinal pigment epithelium (RPE).
  • Geographic refers to the shape of the atrophied portion of the retina, which resembles the irregular outline of a land mass (geography).
  • The RPE helps to maintain the health of the retinal photoreceptor cells, called rods and cones. These photoreceptor cells are triggered by light to set off a series of electrical and chemical reactions that helps the brain to interpret what the eye sees.
  • The degeneration of the RPE cells also leads to the death of the rods and cones.
  • At present, there is no medical or surgical treatment for geographic atrophy.

The First Clinical Trial: Cell-Based Therapy

One treatment for dry AMD that may show promise is cell-based therapy, derived from umbilical cord tissue, called palucorcel. The researchers emphasize that it is not the same as stem cell therapy. Early results from the phase 2 FILLY clinical trial were presented at the American Academy of Optometry 96th Annual Meeting, October 11-14, 2017, in Chicago, Illinois.

More About the Cell-Based Therapy Research

Edited and excerpted from Cell-Based Therapy for Dry AMD Promising in Early Trial, via Medscape:

A cell-based therapy derived from umbilical cord tissue could someday treat geographic atrophy caused by age-related macular degeneration (AMD), early studies of this novel therapy suggest.

Lead investigator Sheila Hickson-Curran, MCOptom, is director of ophthalmology at the Janssen Pharmaceutical Companies of Johnson & Johnson. [Her research team] is developing an injectable cell-based product they have labeled palucorcel.

She emphasized that palucorcel is not stem cell therapy. The cord tissue from which palucorcel was derived for use in this trial came from a baby born approximately nine years ago. One umbilical cord can provide an almost endless number of cells, she said.

Dr. Hickson-Curran was circumspect about the preliminary findings. “We cannot yet claim [effectiveness] because our numbers are small and they do not come from a randomized controlled clinical trial, but this approach definitely has potential,” she said.

“This is the third clinical trial with these cells, and what we have learned is that the cells can improve the vision of some patients with geographic atrophy. In the phase 1 trial, some gained at least 15 letters on [the Early Treatment Diabetic Retinopathy Study] chart, and this was sustained for at least 18 months.”

In her presentation, Dr. Hickson-Curran reported findings from the … phase 2b PRELUDE clinical trial, which will follow patients [for five years]. Twenty-one patients (average age 77 years) with geographic atrophy related to AMD enrolled in the trial.

Thus far, very early findings from the trial show that the procedure proved safe, with no reports of retinal tears or detachments, significant [bleeding], or endophthalmitis (i.e., infection). Optimal placement of [the injected] cells has resulted in maintenance of vision. “These are patients with advanced disease, so we don’t expect [substantial] improvement in vision,” she said.

You can read more about this cell-based therapy, including the injection technique and delivery system used in the research, at Cell-Based Therapy for Dry AMD Promising in Early Trial.

The Second Clinical Trial: APL-2 Injections

Another potential treatment for dry AMD that may show promise is the drug APL-2, which is administered as an eye injection monthly or every other month for 12 months, followed by six months of monitoring after the end of treatment. Researchers have released phase 2 results of the FILLY clinical trial, which included 246 patients across 40 testing sites in the United States, Australia, and New Zealand.

More About the APL-2 Research

Edited and excerpted from New drug reduces rate of progression of incurable eye disease, via Medical Xpress:

An international study has found a way to slow the progression of dry age-related macular degeneration—one of the most common causes of vision loss in people over the age of 50.

The Phase 2 clinical trial (known as the FILLY trial) was sponsored by Apellis Pharmaceuticals and included 246 patients across 40 testing sites in the United States, Australia, and New Zealand. [Editor’s note: You can see the listing of all testing sites in the FILLY clinical trial at Study Contacts and Locations.]

“[Geographic atrophy] (GA) is like having moth-eaten holes in your vision and they slowly all join up in the middle part of the vision, destroying the ability to read, drive, and recognize faces,” [Principal Investigator] Professor Robyn Guymer says.

Apellis Pharmaceuticals developed a new compound called APL-2 for treating patients with GA. Patients were given [eye] injections either monthly or every other month for 12 months, resulting in a reduction in GA lesion growth of 29 per cent and 20 per cent respectively, compared to control patients.

Additionally, …a greater effect was observed during the second six months of the study: a reduction in GA lesion growth rate of 47 per cent with monthly administration, and a reduction of 33 per cent with every other month administration.

Based on these positive results, Apellis plans to proceed with Phase 3 studies as soon as possible.

You can read more about the APL-2 phase 2 clinical trial results at New drug reduces rate of progression of incurable eye disease.

What are Clinical Trials?

In order to receive approval from the U.S. Food and Drug Administration (FDA), a new drug or treatment must be proven to be both safe and effective by undergoing a rigorous series of controlled unbiased studies. To prevent bias, neither the patient nor the examiners can know which patients received the actual treatment and which were the untreated (or “control”) subjects.

These are called “double blind” or “double masked” studies and usually yield the most reliable results. The medication is coded and patients are placed at random into either the treatment or control group. When the study is concluded, the code is revealed and it is then possible to determine who received the actual drug and who received the inactive substance, or placebo.

As defined by the U.S. National Institutes of Health, most clinical trials are designated as Phase 1, 2, or 3, based on the questions the study is seeking to answer:

  • In Phase 1 clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe and effective dosage range, and identify possible side effects.
  • In Phase 2 clinical trials, the study drug or treatment is given to a larger group of people (100-300) to determine if it is effective and to further evaluate its safety.
  • In Phase 3 studies, the study drug or treatment is given to even larger groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
  • In Phase 4 studies, after the Food and Drug Administration has approved the drug, continuing studies will determine additional information, such as the drug’s risks, side effects, benefits, and optimal use.

VisionAware will provide updates on these clinical trials as results become available.

Additional Information About Macular Degeneration