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Technology News for People Who Are Blind or Visually Impaired
From the American Foundation for the Blind
 January 2014 Issue  Volume 15  Number 1

Vision Research

Three New Techniques for Treating Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is the leading cause of blindness in people age 65 and older. Currently, an estimated 13 million people in the US have AMD, and the problem is expected to grow as the population ages. One large study found that people in middle age have about a 2-percent risk of developing AMD. However, by age 75, this risk increases to nearly 30 percent.

Tragically, most people who develop AMD go undiagnosed for up to seven years before the condition is detected and treatment can begin. There is currently no cure for AMD. At best, treatment can slow or sometimes even halt the progression of the disease. Considering the ever-growing number of cases of AMD, with worldwide health care costs rising into the hundreds of billions of dollars per year, scientists have doubled and redoubled their efforts to discover and develop new treatment options. In this article we'll describe three impending breakthroughs: two new treatments for AMD currently in clinical trials, and a brand new device called the AdaptDx, that will allow doctors to detect the onset of the disease almost as soon as it arises.

The AdaptDx Dark Adaptometer

The most common type of macular degeneration is the early or "dry" form of the disease. It occurs when tiny, yellow cholesterol-rich deposits called drusen build up between the retinal pigment epithelium (RPE) cells and the underlying layer of blood vessels. Drusen blocks the retina's ability to rid itself of waste products and to receive essential nutrients from the underlying blood vessels. Over time, the rods and cones that enable us to see begin to weaken and die. Colors grow less vivid, and our sharpest, straight-ahead vision begins to dim and fail.

Eventually, the disease reaches a tipping point, and further vision loss can be both sudden and dramatic. It's not uncommon for a patient to go from 20-20 to legally blind in less than six months. In 20 percent of cases the disease will progress to the even more damaging "wet" form, which can lead to near total blindness and which we will discuss further later in this article.

These changes are permanent. The sooner you can detect AMD and intervene the better. Unfortunately, according to Gregory R. Jackson, PhD, CSO of MacuLogix, Associate Professor of Ophthalmology, and Director of Clinical Research for Ophthalmology at Penn State College of Medicine, "By the time most patients are diagnosed they have already sustained substantial vision loss." Experts estimate that by the time of diagnosis at least 40 percent of patients are legally blind in at least one eye. "The other eye may have been compensating, so the patient isn't even aware he or she has been losing vision until it's too late," Jackson says. "Also, we're getting older, and we may not seek treatment in time because we understandably assume any vision loss is the natural consequence of aging eyes."

For most individuals, an optometrist is the primary vision care specialist. These professionals are not always equipped to detect early AMD, however. "Even retinal specialists can miss up to twenty percent of the subtle changes that signal the onset of the disease," says Jackson.

In the mid 1990s, when Dr. Jackson was studying night vision problems among older adults, he noticed the problems in the back of the eye that led to failing night vision were remarkably similar to the changes associated with AMD. When he redirected is research to study AMD patients, "I was floored by how many of them demonstrated poor night vision, even patients whose vision was otherwise still quite good."

Not only was the night vision in these individuals diminished, it took much longer for AMD patients to adapt from light to dark, when turning off a lamp, for instance, or when exposed to a camera flash. Jackson theorized these changes were at least partially caused by the drusen blocking the passage of vitamin A from the blood vessels to the retinae. Vitamin A is essential for both night vision and "dark adaptation." He also predicted that measuring dark adaptation might be one way to help diagnose AMD sooner than was currently possible. He was right.

"We took his results from the laboratory to the clinic," says John Edwards, who began working with Jackson in 2004. In 2008 they cofounded MacuLogix, and in February 2011 the company received FDA clearance to market their new device: the AdaptDx Dark Adaptometer.

Jackson and Edwards describe the AdaptDx Dark Adaptometer as a sort of stress test for the retina. The tabletop device is a large box, approximately two feet on each side, with a chin rest and eye tunnel at one end where one eye at a time is tested. The room lights are switched off to acclimate the patient to the dark, then, holding a response button in one hand, the test subject peers into the darkened tunnel and focuses on a red dot, which lights the center of a viewing screen at the far end.

The test begins with a bright flash of light to simulate daylight. Then the tunnel returns to darkness, only now a green dot is also projected just below the central, red dot. The subject presses the response button to signal that he or she has detected this green dot. Then it's time to start again.

During each test round, the green dot grows fainter and fainter. "Sort of the way a hearing test plays tones at increasingly lower volumes until eventually you reach a threshold beyond which the subject can no longer hear the sound," Jackson explains.

By comparing the speed of the subject's test responses to healthy norms it's possible to detect the onset of AMD at the very earliest stages, well before there is any vision loss, the appearance of drusen, or other retinal changes an ophthalmologist would currently use to spot AMD. It's also possible to track the course of the disease, and several pharmaceutical companies are already using the device for development of potential new medications.

Currently, the only treatments for early-stage AMD are anti-oxidant vitamins and other nutritional supplements, together with lifestyle changes, such as losing weight and stopping smoking.

"At this stage, it's mostly watchful waiting," says Jackson. "Of course if and when the disease reaches the tipping point where more aggressive drug therapy becomes useful, we'll be able to start those treatments immediately." Until AMD reaches that tipping point, the medications and other treatments discussed in the next section offer little to no value. But when that time does come, beginning treatment even a few months sooner can ultimately make a profound difference in the amount and quality of vision that can be conserved.

Retired hospital worker Joanne Polanichka participated in a clinical study of the AdaptDx Dark Adaptometer in 2011, and just recently she underwent a two-year follow-up. "I am lucky, I still have dry AMD. My vision is still strong, and I was relieved to learn things are stable and have not gotten any worse since my first test," she says. Joanne was first tested for AMD nearly fifteen years ago, after one of her sisters was diagnosed with the wet form of the disease. "My sister had AMD for years before she knew it, and today she has lost most of her vision," she says. Another of Joanne's sisters was also later diagnosed with wet AMD.

The AdaptDx is only now reaching the market, and consequently, it is not yet widely available. Hopefully, however, it won't be too long before early screening for AMD will become as routine and commonplace as testing for glaucoma. Says Joanne, "If we can catch it sooner and start treatment before things get worse, who knows what a difference that could make."

New Hope for Wet AMD

Approximately one in five dry AMD patients go on to develop the wet form of the disease. Overstressed immune cells in the eye begin to fail, and they are no longer able to block the growth of tiny blood vessels that invade the retina and leak blood, which is toxic to rods and cones. These leaking fluids give wet AMD its name, and there is no cure: the goal of treatment is to dry up these fluids and to stop the eye from creating new and fragile blood vessels.

Currently, the most effective treatment for wet AMD is a class of drugs called anti-VEGF medications. Vascular endothelial growth factor (VEGF) is the protein that promotes blood vessel growth, also called angiogenesis. Angiogenesis is necessary for body growth and wound healing, but when it misfires in overstressed retinal cells it can lead to wet AMD. VEGFs can also stimulate certain tumors to transform from benign to malignant, and in fact, the most popular medication for treating wet AMD, Avastin, was originally developed and FDA-approved in 2004 for the treatment of colon cancer.

Avastin and other anti-VGEF medications can only work if they are injected directly into the eye, and most patients require between eight and twelve injections every year to stem the tide of new vessel growth.

"The injections are horrible," says Jonathan Gathorne-Hardy, a noted British biographer, novelist and poet. "It's just nerve wracking to see someone coming toward your eye with a needle. When I had the first injection I jumped, and after the injection the eye felt bruised for days.

It's not a pleasant prospect, especially if it has to be repeated month after month for the rest of your life. Happily, however, researchers are now turning to a different page of that metaphorical Big Book of Cancer Treatments to develop a pair of exciting, high-tech wet AMD therapies that can reduce or even eliminate the need for anti-VEGF injections.

The IRay Radiotherapy System

For decades doctors have treated various cancers with high energy blasts of radiation that destroy the ability of fast-growing tumor cells to reproduce. Combining radiation treatments with traditional chemotherapies allows doctors to battle the cancer on two fronts. Logically, a similar combination of strong drugs and radiation could also be useful in controlling the fast-growing blood vessels associated with wet AMD. But until recently there were two major roadblocks.

"The energy levels of the radiation sources used to treat tumors is extremely high," observes Jim Taylor, CEO of California-based Oraya Therapeutics. "To reach and treat the retina using these oncology systems you would have to send the cell-destroying beam through the front of the eye, and much of this damaging radiation would pass right through the retina and on into other sensitive structures in the eye or into the brain."

The second difficulty in using radiotherapy to treat AMD is keeping the eye perfectly still long enough to administer the treatment. Oraya Therapeutics has solved both of these problems with their new, IRay Radiotherapy System. Here's how.

Instead of a single, strong beam of radiation, the IRay Radiotherapy System uses three tightly-focused, low-energy beams of x-ray radiation from a source no stronger than a dental x-ray or airport baggage scan. The 3.5 millimeter diameter beams are delivered one after the other through three different places across the white of the eye, at approximately the 5, 6 and 7 o'clock positions. "This way we can keep the radiation passing through the front of the eye at a minimum, and still deliver an effective, combined dose to a single target on the macula," says Taylor.

The IRay Radiotherapy System compensates for the weaker beam of radiation by delivering a much longer dose, up to four minutes total for each of the three beams.

Jonathan Gathorne-Hardy was one of the very first patients to receive Oraya Therapy. Jonathon has wet AMD in both eyes, and in August of 2010 he received a single IRay treatment in his stronger, right eye. "They strapped me into position to keep me as still as possible. I looked into the machine for twenty minutes, and then it was over. I was done."

A special contact lens had been placed on Jonathon's eye. A tiny post on the front was gripped by the apparatus to keep his eye more or less immobile while the x-ray source directed its beam through each of the three target positions on the sclera and toward a single spot on the central retina. The post also contained reflective markers that were tracked by an array of video cameras. "The cameras could detect when the post moved too far and the eye was out of position," Taylor explains. "The computer would stop the beam instantly, and not resume until the eye was back in the correct position."

Within weeks the vision in Jonathon's right eye had improved significantly. He wound up with a 9-letter gain on the Early Treatment Diabetic Retinopathy Study (ETDRS) Eye Chart. Today, nearly three years later, Jonathon continues to enjoy a 7-letter improvement. "I haven't needed a single injection in my right eye since the treatment," he reports. Jonathan still receives anti-VEGF injections in his left eye, but he's looking forward to having that eye treated soon, as well.

Jonathon's results are not unique. A recent clinical follow-up of 230 Oraya Therapy patients treated at 21 sites in 5 countries revealed a 45 percent reduction in the number of injections patients needed to keep their AMD stable. Half the patients required only one injection in two years, while a full 23 percent required no injections at all.

As of this writing the IRay Radiotherapy System is only available in the UK and Switzerland, though treatments will also soon commence in Germany. Here in the US, the company is finalizing plans for the final clinical trials necessary for FDA approval.

The SalutarisMD Treatment

A second radiation-based therapy for wet AMD may be poised to launch in the very near future. Salutaris Medical Devices, Inc. (SalutarisMD) is currently testing a handheld ophthalmic device that uses brachytherapy, which involves placing a therapeutic radioisotope as close as possible to the area to be treated, in this case the macula. Here's how it works.

The as-yet-unnamed SalutarisMD device uses a tiny amount of radioactive strontium 90 placed in a sealed, stainless steel canister at the tip of a curved cannula, a small tube used for medical procedures. The patient's eyed is anesthetized, and the pupil is dilated. The retinal specialist then slides the cannula between the eye and the eyelid, avoiding the eye muscles as he gently guides the probe around toward the outside back of the eye.

A fiber optic light at the very tip guides the way. "Using an ophthalmoscope, you can actually see the tiny pinpoint of light shining through the retina, which the doctor can use to move the cannula into position," says SalutarisMD CEO, Michael Voevodsky.

In just a few seconds the cannula is in place, with the tiny canister nestled against the back of the eye nearest the macula. The patient then receives a therapeutic dose of beta radiation lasting between five and six minutes, and then the cannula is removed. Nothing is left behind in the patient. That's it--the treatment is complete.

As with Oraya Therapy, the goal of the Salutaris treatment is to use radiation to cause the AMD lesions to regress, and to block the development and growth of damaging new blood vessels. The company believes their approach offers a targeted treatment that's focused specifically on the wet AMD. "The type of beta radiation we use only travels a very few millimeters," says Voevodsky. "So the exposure is limited almost exclusively to the macula, where it can do the most good."

In a recent clinical study performed in conjunction with the University of Arizona, six patients received the Salutaris MD procedure and were given monthly follow-up examinations. After three months all six experienced increases in "best corrected visual acuity" as measured by the ETDRS Eye Chart. After two years, four of the six patients still showed improved vision, and two had still not needed any anti-VGEF injections.

The Salutaris MD device is currently only licensed to treat wet AMD as an investigational device here in the US. The company is also working with Moorefields Eye Hospital in London, where they hope to begin further clinical trials within the year.

Contact Information

MacuLogix, Inc.
Address: 1214 Research Boulevard Hummelstown, PA 17036
Phone: 717-583-1220
E-mail: info@maculogix.com

Oraya Therapeutics, Inc.
Address: 8000 Jarvis Ave. Suite # 200 Newark, CA 94560
Phone: 510-456-3700
Fax: 510-739-1902
UK: 0800 690 6495
E-mail: info@orayainc.com

Salutaris Medical Devices, Inc. (SalutarisMD®)
Address: 4330 North Campbell Avenue, Suite 250 Tucson, AZ 85718
Phone: 520-638-7518
International: 00-1-520-638-7518
E-mail contact form: http://salutarismd.com/contact-us/

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