Summary of Research and Developments in Macular Degeneration, 2011-2012

by Dan Roberts
June 2012
Introduction
Here is MD Support’s summary of the the past twelve months of significant research and development in the field of macular degeneration.
We begin with the field that has been making the most news: pharmacology.
_______________________________
PHARMACOLOGY
SEP: Infection Risk From Repackaged Avastin
The big pharmaceutical news of the year surrounded anti-VEGF drugs for treatment of wet AMD. Anti-VEGF drugs are injected into the eyeball to halt the growth and leakage of blood vessels into the retina that can lead to quick central vision loss. The leading approved drugs are Lucentis and Eylea, while a similar drug, Avastin, is being used off-label for the same purpose at a much lower cost. Repackaging by a pharmacy, however, is required to prepare Avastin for injection at proper dosages.
In September, the FDA alerted the public that repackaged intravitreal injections of off-label Avastin caused a cluster of strep infections in twelve patients in Florida, where investigators traced the tainted drug to a single pharmacy. Soon after, contamination was also reported in Tennessee and California. This is a risk that Genentech, the maker of the drug, warned about when doctors began using the cancer drug Avastin in place of their approved drug, Lucentis.
Reacting quickly to the reports of infection, the Department of Veterans Affairs (VA) ceased using Avastin to treat wet AMD until it could investigate the problem. Then, in November, the VA announced the reinstatement of Avastin on three conditions: 1) that the physician use only one dose per patient from each manufacturer’s vial, 2) that patients be carefully screened before receiving treatment, and 3) that patients be fully informed of the health risks associated with off-label therapy.
Many patients contacted MD Support asking what they should do to ensure their safety. Our recommendation was to learn about the benefits and risks of all three available treatments, and then decide which is better in the patient’s individual case. It is the doctor’s obligation to ensure that the patient has a full understanding before agreeing to receivng Avastin off-label.
Ophthalmic use of Avastin has recently been shown to be generally as safe and effective as Lucentis. Since, however, both the Food an Drug Administration and the Center for Disease Control have established clear warnings and specific guidelines about repackaging drugs, and since those guidelines are generally being ignored in the use of off-label Avastin, a patient’s safest option is to stick with proven drugs that don’t require compounding by a second party. In his article, “The Misuse of Compounding By Pharmacists”, Bruce A. Bouts, MD recommends that our best practice would be to:
1. Avoid compounded agents when sterility is important (e.g., injectable or inhalation agents).
2. Avoid a compounded product when a generic or brand-name agent is readily available.
________________________
NOVEMBER: New Anti-VEGF Drug Approved
In November, our attention was drawn to FDA approval of the newest anti-VEGF drug, Eylea, as a treatment for wet AMD. In trials, Eylea injected into the eye every two months was found to be as effective as monthly doses of Lucentis. The most striking improvement is that monthly monitoring of patients receiving Eylea is not necessary. The longer time between injections (up to two months) helps relieve some of the treatment and cost burden of other anti-VEGF drugs.
This would seem to give Regeneron (the company that makes Eylea) the edge over Genentech, makers of Lucentis. And it did indeed take over a large share of the market within only a few months. Genentech and its European counterpart, Novartis, however, are remaining big players by working toward first approval of Lucentis for use in treatment of diabetic macular edema.
Another development from Genentech may soon be sustained long-term delivery of Lucentis via an implanted ocular device. This would replace the current procedure of periodically injecting the drug into the eyeball.
The device can be implanted into the eye in a 15 minute out-patient procedure. The implant can hold and release four months worth of Lucentis, and it can be resupplied through a permanent opening where it attaches to the sclera (the white outer shell of the eyeball). About 100 implants have been accomplished to date, and the results are consistent with the traditional injection procedure. According to Genentech, The patient would not be aware of the device, and it can be seen only upon examination through the dilated pupil. Trials are expected to begin soon, with clinical use possible in as little as two years.
MAY: MC-1101 for Dry AMD
In May of this year, a topically administered eye drop drug called MC-1101 was introduced as a potential for treating and stopping the progression of AMD from the dry form to the wet form. The drug, being tested by MacuCLEAR, Inc., works by increasing ocular blood flow in the choroidal vessels.
The company has completed a successful Phase 1 human clinical trial for MC-1101 which showed that the drug is safe and well tolerated. The next phase of the study will track visual improvement in 60 patients, with the hope that a treatment for dry AMD will soon make it to the clinics.
But now some disappointing news. Fenretinide, a drug that has been used to treat certain cancers, rheumatoid arthritis, acne, and psoriasis, was found several years ago to slow the production and accumulation of a toxin that leads to vision loss in a juenile form of macular degeneration called Stargardt disease. Trials showed that the drug also reduced the incidence of choroidal neovascularization by about 50 percent in patients with dry AMD.
This was promising news worth following, but the developer, Sirion Therapeutics, announced in February that the trials had been suspended. The FDA ruled that the Phase 2 results were flawed, and, at this point, the high cost of continuing the trials has halted further research.
_____________________________________________
SURGERY
NOV: Implantable Miniature Telescope
In the field of surgery this past year, we heard about approval of the implantable miniature telesope, ongoing stem cell research, and an interesting development in treatment for cataracts.
You may remember that the implantable miniature telescope (IMT) was approved by the FDA back in July 2010 for use as a prosthetic device in the eye. Then, in September 2011, VisionCare Ophthalmic Technologies, Inc. announced that outpatient facilities could obtain Medicare and Medicaid reimbursement for the procedure. Two months later, the company announced that the first patient had received the device.
The pea-sized telescope implant is designed to improve visual acuity. Eligible patients must have central vision blindness and have either stopped responding to AMD medications or have a form of the disease for which no treatment is available. The magnification provided by the implant reduces the impact of the blind spot caused by end-stage AMD. Patients and physicians can find more information about the IMT at www.centrasight.com.
JAN: Stem Cell Study
Another bit of good news came in January of this year from Advanced Cell Technology, when the company reported the first use of human embryonic stem cells to treat macular degeneration in human beings.
The study began with one elderly patient and one young patient with different forms of macular degeneration that had led to severe vision loss. The transplants appeared safe after four months, and both patients had some improvement in vision. The future therapeutic goal will be to treat patients earlier in the disease process, in order to boost the prospects of improving or retaining sight in new patients.
The authors say that, in patients who begin with poor vision, it is difficult to ascertain definite improvements in vision unless such improvements are spectacular. While neither patient lost vision, some standard tests suggested vision had improved in both. The younger patient with Stargardt’s disease went from being able to see only hand movements at first to being able to see single finger movements.
The study is expected to continue into 2014, beginning with 12 patients and eventually including a much larger population. Clinical trial sites have been established so far at Jules Stein Eye Institute in Los Angeles, Wills Eye Institute in Philadelphia, Bascom Palmer Eye Institute in Miami, and Massachusetts Eye and Ear Infirmary in Boston.
FEB: Radiation Therapy
Five years ago, NeoVista, Inc. began trials to study the effects of radiation therapy in combination with Lucentis injection for treatment of wet AMD. The therapy was intended to complement the drug injection by extending the time between treatments. Unfortunately, the company reported in February that Phase III of the study did not meet it’s primary endpoint at two years, becoming the second major trial to fall by the wayside this past year.
FEB: HuCNS Cells
Returning to a more positive note, we heard good news in February about stem cell research from StemCells, Inc. They announced that the FDA authorized a trial of a new method using stem cells from the brain to prevent degeneration of the macula in dry AMD patients.
Purified human neural (HuCNS) stem cells will be administered by a single injection into the space beneath the retina. Patients’ vision will be evaluated over a one-year period, then followed for an additional four years in a separate observational study.
Preclinical data submitted by the Company demonstrated that the stem cell transplants significantly protect against the degeneration of the existing sight cells. Moreover, the number of cone cells (which are responsible for central vision) remains constant over an extended period. This approach is expected to offer a safe, effective and simple treatment that differs from approaches that aim to replace the sight cells.
APR: Cataract Surgery and Alzheimer’s
Our final report in the surgery department comes from a study showing that cataract surgery can relieve Alzheimer’s symptoms in some people.
As reported by the researchers in April, one in four patients showed improvements in thinking and memory skills after replacement with a clear lens. Many also showed an easing of symptoms of depression, and most of the participants also slept better after the surgery. They did not show improvements in day-to-day functioning, but all-in-all, that’s not bad, considering they could do all that and see better, too.
__________________________________
NUTRITION
NOV: Vitamins and Aspirin
Moving on to developments in the field of eye health and nutrition, two studies published last year caused some concern in the low vision community about possible harm from vitamins and aspirin. We may be worrying more than necessary, however, due to the way the study results were reported.
One study concluded that “several commonly used dietary vitamin and mineral supplements may be associated with increased total mortality”. The other study revealed that frequent aspirin use is associated with early AMD and wet late AMD.
Both of these studies have three things in common: 1) use of terms like “associated”, 2) the absence of cause and effect in the study designs, and 3) media distortion of the facts.
We must remember that a certain intervention “may be associated” with macular degeneration, but it does not necessarily cause the disease or its progression. For example, a person may be taking regular dosages of aspirin to alleviate a cardiovascular problem. At the same time, that person may have macular degeneration caused by the same inflammatory response responsible for the cardiovascular condition. There would, therefore, appear to be an association between aspirin and macular degeneration.
The researchers are aware of this, which is why they have not said conclusively that either vitamins or aspirin are going to harm us. They simply say that an association has been found and that further study is necessary before making such claims. It is the media that often carries it to that next step. We must, therefore, think twice about such reports and consult with professionals before changing our course of treatment.
AREDS2
Since 2006, the National Institutes of Health (NIH) have been conducting a nationwide study to see if a modified combination of vitamins, minerals, and fish oil can further slow the progression of vision loss from AMD.
This new study, called the Age-Related Eye Disease Study 2 (AREDS2), builds upon results from the first AREDS research. That study, completed in 2001, found that high-doses of vitamins C and E, beta-carotene, zinc, and copper, taken by mouth, reduced the risk of progression to advanced AMD by 25 percent, and lowered the risk of moderate vision loss by 19 percent.
AREDS2 will refine the findings of the original study by adding the antioxidants lutein and zeaxanthin and the omega-3 fatty acids DHA and EPA to the formulation. The main objective is to determine if these nutrients will also help decrease a person’s risk of progression to advanced AMD. Previous observational studies have suggested that these nutrients may protect vision.
In addition to including these nutrients, the study is also looking at eliminating beta-carotene from the original formula, due to findings that it may be a risk for cancer in some people, and it is decreasing the amount of zinc. Findings from the study are expected in 2013, but manufacturers are already making the AREDS2 formula available based upon a preponderance of evidence in its favor.
________________________________________
GENETICS
NOV: CFH
In the area of gene replacement research, three events caught our attention during the past twelve months. We learned in November that investigators had identified a rare, high-risk mutation resulting in a loss of function of an important protein called Complement Factor H (CFH). CFH helps control the body’s immune response and inflammation, and mutation of this protein has been suspected for several years to be a cause of AMD in as many as 50% of cases. Now a newly-discovered mutation, more clearly links the CFH gene dysfunction to the disease and may lead to new and effective preventative treatments for high risk individuals.
APR: AVA-101
In April, we heard about a single injection of a new gene therapy treatment from Avalanche Biotech that could possibly stop blood vessel growth and leakage in the wet form of AMD for several years. An injection of a drug called AVA-101 creates a kind of BioFactory that continuously secretes a therapeutic protein over an extended period. This avoids the need for frequent injections, as is now the practice.
Based on preclinical studies, the therapeutic effect will be maintained for at least 18 months and has the potential to last for several years. Human clinical trials are currently underway.
MAY: IL-18
In May, a new finding made the news as yet another possible treatment for wet AMD. Inflammation in the retina results from blood vessel development, and the natural component named IL-18 has been found to keep the process under control. By injecting the chemical into the eye, or by injecting a gene that produces IL-18, the scientists are speculating that they can keep dry AMD from developing into wet AMD. In other words, it would be a preventative treatment, similar to a vaccination.
This discovery was the first step in a long road to clinical application. It must first be tested in animals, then go through human clinical trials, so we are looking at about 10 years of intensive lab work and fund raising. If results from other treatment experiments underway don’t come sooner, at least this offers another reason for hope.
____________________________________________
TECHNOLOGY
New Vision Enhancement System
And finally, technology continues to make strides. One development is a new vision enhancement system that may one day provide something like sight for people who are blind or extremely visually impaired. The system is being developed as a result of military-related trauma research.
It involves computer technology, a cell phone, an auditory feedback device, and an eyeglass-mounted camera to capture objects in the user’s visual field. Information about the visual field is conveyed to the user wirelessly to assist in finding objects or avoiding hazards.
Developers say that, though the technology focuses on military vision trauma, it could also be used by people with age-related and other forms of macular degeneration.
iPAD3
And, of course, 2012 has brought the latest generation of the Apple iPad to market. The iPad3 has a higher screen resolution than the iPad2, a better camera, and stronger wi-fi (at extra cost). Other than that, it is essentially the same as it’s older brother, and the changes may be too negligible for you to upgrade. On the other hand, if you don’t already own an iPad, you can find really good deals on the older models for less than $350. Considering all of its accessible features for low vision people, it might be worth looking into.
Driving
Another exciting technological development is the self-driving automobile. It has been road tested now for thousands of miles, and it looks like it will actually become a reality in a few years. In case you think you couldn’t afford one (and how many people could?), don’t worry. They are being seriously considered for use as taxis, so they will be available to all of us. And we won’t have to talk to them about the weather, or why they drove a mile out of our way to get us to the grocery store on the next block. Just pick up a phone, say “pick me up”, and it will come right to your front door.
This kind of thing, along with vision restoration and cures, could conceivably become realities in our lifetimes. We are hearing about an ever-increasing number of such achievements in the areas of surgery, nutrition, pharmacology, and technology. We have also witnessed some failures, but failure often leads to better knowledge.
And remember, we are not only patients. We are also in a position to teach those who follow us. Please take every opportunity to pass along this information to family members and friends. And if they want to keep up through the year, invite them to join one of our live support groups, or tell them about our website at www.mdsupport.org.
Here’s to another year of promising work on behalf of our low vision community.

Summary of Research and Developments in Macular Degeneration: 2009-2010

by Dan Roberts
June 10, 2010
Introduction
If I were to describe the past twelve months in a word, it would be “progress.” No spectacular breakthroughs have occurred during that time to make big news in the AMD world, but a lot of persistent work has been reaping promising results. moving us ever closer to effective treatments. Even the cure we hope for is now being thought of more in terms of “sooner” than “later.”
This summary is a brief overview of the news that has been of interest to us during the period of June 2009 through May 2010. More details about the reports from the 2009 Meeting of the American Academy of Ophthalmology (AAO) may be found on this site. Other reports in this summary are annotated with sources for further reference.
I’ll begin by mentioning two studies in the area of nutrition, since nutraceuticals are currently our most immediate hope for slowing the progression of vision loss from AMD.
NUTRACEUTICAL
1. Omega-3 Lowers AMD Risk
For the past couple of years, we have been made aware of the benefits of Omega-3 fatty acids in our diet, and nutritionists have been recommending several servings of fish each week or supplementation with fish oil. To further confirm these benefits, 671 subjects in the 2009 ALIENOR Study were given eye examinations seven years after plasma fatty acid measurement. As hoped, lower risk of geographic atrophy (advanced dry AMD) was associated with higher plasma levels of total omega-3 fatty acids, in accordance with previous studies of dietary intake.
Ref: AAO 2009 Paper: “Plasma Omega 3 Fatty Acids and Risk for Age-Related Maculopathy: The ALIENOR Study” (Presenting Author: Jean-Francois Korobelnik MD)
_______________________
2. Saffron Improves Vision
Another interesting finding was reported in March 2010, when clinical trials in Italy and Australia showed that the spice, saffron, can improve vision in people with AMD.
Subjects experienced up to 2 lines of improvement in their vision while taking saffron pills, but the effect quickly disappeared when the dose was discontinued. This indicates that it may improve the vision function of surviving cells but it does not reverse the damage that is already present.
If you intend to add saffron to your diet, be sure you are actually purchasing saffron, not safflower, which is sold as saffron by some unscrupulous dealers.
Ref: www.mdsupport.org/library/saffron.html
________________________
SURGICAL
Seven surgical procedures headed the news during these past 12 months.
1. FDA Considering Approval of IMT
The investigational implantable miniature telescope (IMT), discussed here last year, is designed to be a solution for moderate to profound vision loss due to advanced, end-stage forms of AMD that have no current surgical or medical treatment options.
If you remember, the telescope prosthetic device, which is smaller than a pea, is implanted in one eye during an outpatient surgical procedure. In the implanted eye, the device renders enlarged central vision images over a wide area of the retina to improve central vision, while the non-operated eye provides peripheral vision for mobility and orientation. On March 27, 2009, the FDA Ophthalmic Devices Advisory Panel unanimously recommended that the FDA approve, with conditions, the premarket application of the IMT for End-Stage AMD. The device has received CE Mark approval in Europe, but we are still waiting for approval in the US at this time. No explanation has yet been given for the delay.
Ref: AAO 2009 Session: “Implantable Miniaturized Telescope” (Presenter: Mark R. Wilkins, MD)
Ref: www.mdsupport.org/library/imt.html
________________________
2. LMI Approved in Europe
In 2007, Optolight Vision Technology announced success from implantation of the LMI, which is a second generation of the implantable miniature telescope. They reported that the LMI may be an effective solution for optical rehabilitation of patients with ARMD or other macular pathology by increasing the central image on the retina while preserving peripheral vision. This preservation of the peripheral field is the main difference between the LMI and the IMT, allowing it to be implanted in both eyes.
On June 17, 2009, OptoLight Vision Technology announced that it received CE mark approval in Europe, which allowed OptoLight to immediately begin marketing the implant in Europe and other markets outside of the United States.
Ref: www.mdsupport.org/library/lmi.html
________________________
3. Skin Cells Changed Into Retina Tissue
In August 2009, scientists at the University of Wisconsin-Madison reported that they had reprogrammed skin cells and turned them into different kinds of retinal cells. The work added to a growing weight of evidence that stem cells made by reprogramming have similar, if not the same, abilities as the more controversial embryonic stem cells.
Scientists may now be able to take a skin biopsy from someone with a vision ailment, create retinal cells, and observe how the disease unfolds and how the cells die over time. They hope to also use reprogramming as a way to generate damaged or diseased cells on which pharmaceutical companies can test their drugs and to find ways to correct genetic defects.
Farthest off, but most exciting to many researchers, is the possibility of using reprogramming to produce healthy cells that can replace those that have died.
Ref: “Skin Cells Changed Into Retina Tissue,” by Mark Johnson (Journal Sentinel Online.
August 24, 2009)
______________________
4. UCI Researchers Create Retina
As recently as the end of May 2010, University of California Irvine scientists have created an eight-layer animal retina from human embryonic stem cells. This is the first three dimensional tissue structure to be made from stem cells, and it could be a big step toward retina replacement in eyes affected by macular degeneration. It is an advancement over creation of single cell layers, since the multi-layered human retina might then be replaced in its entirety in one procedure.
The researchers are testing the early-stage retinas in animal models, in hopes that success will lead to human clinical trials.
Ref: today.uci.edu
______________________
5. Brachytherapy May Improve Vision
Epimacular brachytherapy involves radiation treatment delivered by a small plaque sewn to the sclera (the white covering of the eyeball). In November 2009, NeoVista, Inc. announced results from a study designed to examine the company’s brachytherapy procedure when used in patients undergoing anti-VEGF drug injections for wet AMD.
Preliminary study results suggest that a single procedure of epimacular brachytherapy can further improve visual acuity in a majority of this patient population while decreasing the number of injections required. Most importantly, they researchers reported, 63% of patients enrolled in the study experienced improvement in their visual acuity, while 50% of patients gained 5 or more letters of visual acuity at 6 months.
Ref: www.neovistainc.com/meritage.html
_____________________
6. New Radiation Treatment Under Study
Another radiation therapy system entering trials this past year was the Oraya IRay system. This delivers a robotically controlled dose of low-energy X-ray radiation to the retina.
Oraya Therapeutics, Inc. began enrolling patients at seven European sites to demonstrate the safety and effectiveness of radiation therapy for the treatment of wet AMD. According to the company, the radiation dosages close inflammation mediated capillaries and further stop the inflammatory process that leads to wet AMD. In this study, the procedure is used in conjunction with anti-VEGF injections.”
Ref: www.orayainc.com/clinicaltrials.asp
_____________________
7. Tinted IOLs May Slow AMD
A 2009 study showed that implantation of a blue light-filtering intraocular lens (IOL) at the time of cataract surgery increases macular pigment in the retina. This increase may provide protection against the development and/or progression of AMD.
Macular pigment is thought to protect against AMD by absorbing blue light before it reaches the photoreceptors in the retina. The retina is exposed to as much as six times the amount of blue light in a person having the lowest level of macular pigment when compared to a person with the highest level. This gives rise to the belief that blocking blue light with replacement IOLs and other types of protective lenses may help slow down the disease process.
Ref: Macular Pigment Research Group: www.mprg.ie
___________________
PHARMACEUTICAL
The pharmaceutical industry leads the way this year, with nine newsworthy headlines.
1. Fenretinide Granted Fast-Track Status
Fenretinide (ST-602), a drug that has been used to treat certain cancers, rheumatoid arthritis, acne, and psoriasis, has been found to also slow the production and accumulation of a toxin called A2E that leads to buildup of lipofuscin (waste deposits) in the retina, resulting in vision loss in people with dry AMD. If the drug proves effective with dry AMD patients, it may then also be used off-label for treatment of Stargardt’s disease, a juvenile form of macular degeneration.
The trials, which began in 2006, were granted fast-track designation in April 2009, based upon strong results from phase 2.
Ref: ARVO 2009 Paper: “Fenretinide for the Treatment of Geographic Atrophy in Patients with AMD: One-Year Interim Analysis” (Presenting Author: Roger Vogel MD)
________________________
2. Lucentis Still the Gold Standard
Incidence of ocular and non-ocular safety events continues to be low and consistent with prior Lucentis trials. For 600 patients who received Lucentis in prior trials, the most common ocular adverse events over 2 years have been worsening macular degeneration (35%), retinal hemorrhage (25%), and conjunctival hemorrhage (25%). Lucentis is still showing excellent results, and it is still considered the gold standard for treatment of wet AMD.
Ref: AAO 2009 Paper: “Safety Outcomes Over 2 Years in the HORIZON Extension Trial of Ranibizumab (Lucentis) in Neovascular AMD” (Presenting Author: Matthew S Benz MD)
________________________
3. POT-4 Found Safe and Effective
POT-4 is a synthetic peptide that has been found to inhibit a genetic process that can lead to local inflammation, tissue damage (as in dry AMD) and the resulting blood vessel growth in wet AMD. Inflammation is thought to be the cause of AMD in as many as 50% of cases, so a good deal of research is being done in this area.
It was reported in 2009 that phase 1 studies found POT-4 to be well tolerated, safe, and effective in improving macular edema.
Ref: AAO 2009 Paper: “Phase 1 Results of the Complement C3 Inhibitor POT-4 in AMD” (Presenting Author: Philip J Rosenfeld MD PhD)
________________________
4. VEGF Trap-Eye Completes Phase 2
AAO 2009 Poster: “VEGF Trap-Eye Vision-Specific Quality of Life Through 52 Weeks in Patients With Neovascular AMD in CLEAR-IT 2: A Phase 2 Clinical Trial” (Presenting Author: Allen C Ho MD)
VEGF Trap-Eye is a molecule which has been shown to block choroidal neovascularization (blood vessel growth) in eyes with wet AMD. Two studies were reported in 2009 to have been successful in both improvement of the affected retina and improvement in patients’ quality of life.
AAO 2009 Poster: “OCT and Fluorescein Angiography Outcomes Through 1 Year for a Phase 2 Study of Intravitreal VEGF Trap-Eye in Neovascular AMD” (Presenting Author: Peter K Kaiser MD)
________________________
5. Oral Drug For Dry AMD Enters Phase 2
Following the success of the Phase I clinical trial, Acucela Inc. has begun recruiting participants with dry AMD for a Phase II study of the oral drug ACU-4429 for dry AMD. Known as the ENVISION Clarity Trial, Acucela is planning to enroll at least 56 participants at multiple sites throughout the U.S. Participants will receive either the drug or a placebo.
Ref: www.medicalnewstoday.com/articles/149919.php
________________________
6. Alzheimer’s Disease Treatment May Benefit AMD Patients
Copaxone (glatiramer acetate) injections are given in Alzheimer’s disease to decrease destructive beta-amyloid deposits. These deposits are similar to the proteins seen in
drusen found in dry AMD, so researchers are trying copaxone for treatment of dry AMD. In week 12 of a small preliminary study, 4 eyes (3 patients) treated with copaxone showed a total reduction of drusen area from baseline of 66%. Two eyes receiving sham injection had essentially no significant change in drusen area.
Ref: www.medscape.com/viewarticle/564015_2
_______________________
7. MC-1101 Eye Drop For Wet AMD Proves Safe
MC-1101 is an eye drop which affects the blood flow in the choroid, hopefully stopping the progression of AMD. So far, a small Phase 1 study by MacuCLEAR, Inc. has established the safety of seven dosages over three days, and plans for further trials are underway.
Ref: www.macuclear.com
_______________________
8. Aspirin May Aggravate AMD
We have been told that aspirin might help to inhibit the inflammation process, thereby slowing the progression of AMD. But here is frustrating news of a study just completed that suggests aspirin might actually be somehow associated with progression of the disease. 4691 patients 65 years and older were asked about their use of aspirin and about other possible risk factors for aging macula disorders. The results showed that odds ratios for all grades of early aging macula disorder rose with increasing aspirin intake frequency for subjects who reported daily use. The researchers, therefore, concluded that frequent aspirin use seems to be harmful for aging macula disorder in older populations.
Study leader Dr. Paulus de Jong said, however, that patients with cardiovascular disease should not stop taking aspirin. “But if they are taking it as a pain killer, there are other medications they can use.”
Of course, more study is needed before definite conclusions can be drawn, and other studies have shown no correlation, even beneficial correlations, between aspirin and macula disorders. But moderate intake of aspirin might be something we need to consider until more is known.
Ref: Association for Research in Vision and Ophthalmology (AAO) 2010 Annual Meeting: Abstract 1620. Presented May 3, 2010.
_______________________
9. Studies Show Lucentis and Avastin to be Equal
In February 2010, investigators at Kaiser Permanente Southern California in Pasadena reported that Avastin and Lucentis performed equally. Of 452 patients treated for wet AMD, 22.9 percent of Avastin patients and 25.0 percent of Lucentis patients attained visual acuity better than or equal to 20/40 after a year of treatment. Similar numbers of patients in each
group also showed some degree of vision improvement at 12 months.
The Kaiser Permanente study is one of several comparing the two drugs. The largest, and probably most definitive, study is the National Eye Institute’s ongoing Comparisons of Age-Related Macular Degeneration Treatments Trials (CATT), with results expected next year. Avastin, originally designed as a cancer drug, is administered off-label, but research like the Kaiser study has been showing it to be at least as safe and effective as Lucentis for use in treatment of wet AMD.
We should remember that the comparison trials will not lead to FDA approval of Avastin for treatment of wet AMD. It may or may not confirm what we already know, but the drug will, in either case, remain on off-label status. Since large scale Avastin trials by the parent company, Genentech, are not likely, this will still be considered a safety issue.
Ref: Ophthalmology (Feb 2010)
Ref: www.mdsupport.org/library/catt.html
Drugs Under Study For Wet AMD
Here is a list of drugs currently under study for treatment of wet AMD. Three of them (Macugen, Lucentis and Avastin) have already entered clinical use, but followup studies continue to confirm their safety and efficacy.
Macugen
Lucentis (ranibizumab)
Avastin (bevacizumab)
Verteporfin PDT (in combination)
Tryptophanyl-tRNA synthetase (TrpRS)
AdPEDF
VEGF-TRAP-EYE
AG-013958
JSM6427
TG100801
ATG3
Perceiva
Endostatin
Pazopanib
siRNA
Ref: www.mdsupport.org/library/anti-angio.html
_______________________
Drugs Under Study For Dry AMD
Here is a shorter list, but still encouraging, of drugs under study for potential treatment of the dry form of AMD:
ACU-4429
Copaxone
Fenretinide (ST-602)
Iluvian (fluocinolone acetonide)
MC-1101
OT-551
POT-4
Retinylamine
Ref: www.mdsupport.org/library/treatments.html
_______________________
So there are at least 23 chances for treatments or cures from the pharmaceutical industry.If I haven’t mentioned them in this summary, it’s because most are still in the trial process, with no significant findings to report as yet. We may not hear very much about this work in the daily news, but rest assudred that the race is on, and no matter who reaches the finish line first, we, the patients–or at least our children and grandchildren–are going to be the eventual winners.
GENETICS
A great deal of research is being carried out in the field of genetics, as this is very likely where the cures for most diseases will be found. Two developments have stood out during the past 12 months.
1. RPE65 Gene Therapy Showing Promise
First, three young adults who received gene therapy for Leber congenital amaurosis (LCA), a blinding eye condition, remained healthy and maintained previous visual gains one year later. One patient also noticed a visual improvement that helped her perform daily tasks.
In this study, researchers injected healthy copies of the RPE65 gene under a healthy area of the retina in an attempt to repair the visual cycle. One year after the procedure, evidence shows that the newly introduced gene is functional and is increasing the light sensitivity of the retina.
This is the first study that reports the one-year safety and effectiveness of successful gene therapy for LCA. It paves the way for similar techniques, which can eventually be applied to other genetic diseases such as AMD.
Ref: www.mdsupport.org/library/breakthrough.html
________________________
2. PEG-POD: A New Gene Delivery Tool
The second bit of news came in January 2010, when researchers reported having developed a new tool for gene therapy which significantly increases gene delivery to cells in the retina compared to other carriers and DNA alone.
A peptide called PEG-POD provides a safe and effective vehicle for transferring DNA into cells without using a virus, currently the most common means of DNA delivery. PEG-POD protects DNA from damage in the bloodstream, allowing for gene therapy treatments that can be administered through an IV and directed to many other parts of the body.
The researchers found that gene expression in specimens injected with PEG-POD was 215 times more effective than two other carriers tested.
Ref: www.mdsupport.org/library/PEG-POD.html
_________________________
Envisioning A Cure For AMD (by Rick Trevino, OD)
I would like to quote from an article by Dr. Rick Travino, who is active in our online community and who hosts one of the most informative web sites about vision research and developments. In his commentary, “Envisioning A Cure For AMD,” he wrote:
“One of the most exciting developments in the field of AMD research has been the discovery of a relatively small number of genes that seems to control a large amount of the risk of developing the disease.
“Most of the genes that are known to influence the risk of developing AMD involve various components of the complement cascade. Most prominent among these is complement factor H (CFH); however, variants in genes coding for other components of the complement system have also been discovered and shown to be associated with AMD risk and protection. The complement system is very important in regulating the body’s immune system and directing inflammatory processes. Several lines of evidence suggest that dysregulation of inflammation plays a key role in the development of AMD.
“Now, thanks to these discoveries, we are beginning to see treatments that are specifically tailored to address abnormalities in the complement system. This raises the very real possibility of a truly preventative treatment, or even a cure, for the disease. . . Many . . . complement pathway-modulating compounds are currently being considered for, and/or are under, preclinical development for possible use in AMD.
“One could imagine a day when persons are screened at an early age to determine whether they harbor the genes that will ultimately lead them to develop AMD later in life. Then, based upon their specific genetic make-up, persons could take medications, or perhaps undergo gene therapy, that will prevent AMD from ever occurring. In this scenario, the eradication of AMD is a real possibility.”
Thank you, Dr. Trevino for reinforcing our hope for the future.
Ref: www.myvisiontest.com
GOOD NEWS
Incidence of AMD Declining
And finally, to continue on a positive note, I reported last year that a recent study found a lower 5-year incidence of early AMD in patients born or examined more recently, compared to similarly aged persons born or examined in an earlier period. That study included 2,968 participants with early AMD and 3,588 participants with late stage AMD, all of whom were examined at 5-year intervals between 1988 and 2005 as part of the Beaver Dam Eye Study.
Now we have more good news along those same lines. A new study reported this year has shown a 68% lower incidence of macular degeneration in the Baby Boom population. The research suggests that improvements in environment, behaviors, and other such modifiable factors may have contributed to the results. The “birth cohort” effect remained even after adjusting for AMD risk factors such as obesity, heavy drinking, and sunlight exposure.
More study is necessary as the younger population continues to age, but the results further emphasize the importance of environmental and lifestyle factors to retinal health.
Source: Karen J. Cruickshanks, MD (University of Wisconsin School of Medicine and Public Health in Madison) and reported at the Association for Research in Vision and
Ophthalmology (AAO) 2010.
____________________
Conclusion
One of the worst aspects of living with macular degeneration is that there is little we can do about our inevitable loss of vision. To alleviate some of the frustration that causes, we want to leave no stone unturned in our daily battle to maintain our healthiest eyesight.
I hope our news updates and annual summaries are serving that purpose by providing you with some comfort in knowing about all the good research being done. With this kind of information in hand, we no longer have to say, “Why didn’t someone tell me?”
Now, please accept the challenge of passing this information along. Educating others is one of the best ways to keep from being victimized by this disease, and your help is greatly appreciated!