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.
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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.
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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.
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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.
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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.
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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.
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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, 2010-2011

by Dan Roberts
June 19, 2011
Introduction
Since 2006, I have done my best to condense the high points of the previous year’s macular degeneration research into a single report that is concise and understandable for the layperson. I do so, because I understand first hand how important it is to be aware of everything being done on our behalf by the scientific community. Fear of the unknown is often the worst part of this disease. Information, therefore, is an effective weapon that we should all have access to.
Developments in the field of low vision treatment are occurring at an exponential rate. So fast that vision restoration and cures could conceivably become realities in some of our lifetimes. Through the years, we have seen impressive achievements in the areas of surgery, nutrition, and pharmacology. This past year, pharmacology has taken the lead, so most of this summary will discuss the drugs that are now under development and in clinical trials.
PHARMACOLOGY
Results From the Comparison of AMD Treatments Trial (CATT)
The most interesting development this past year was the findings from the Comparison of AMD Treatments Trial (CATT), sponsored by the National Eye Institute. This trial was designed to study the relative safety and efficacy of Genentech’s Lucentis, the approved treatment for wet AMD, and off-label Avastin, a similar, but less expensive drug originally developed by the same company for treatment of colon cancer. At the end of the first year of the two-year trial, the two compounds have been found to be extremely similar in their improvement of mean visual acuity and in the occurrence of adverse events.
These are top line results, with more detail to come later. Meanwhile, the subjects will continue under observation as the trial proceeds through its second year. Five related trials are also underway in the UK and Europe, all of which deserve watching for potential new findings.
In addition to the general findings, the results also revealed surprisingly little difference in the efficacy of scheduled injections and the efficacy of injections delivered on an as-needed basis for both drugs.
The general consensus of opinion among doctors using Avastin is that they will continue using the drug off-label. At the same time, they will ensure that patients are fully aware of adverse events (SAE) that have been determined at this time to be neither significant nor insignificant to the end results. No discussions have yet been held with the Centers for Medicare and Medicaid Services (CMS) regarding changes in policy for reimbursement for Avastin as a treatment for wet AMD.
Another report will be published following conclusion of the trials next year. Meanwhile, it is important that patients discuss their treatment with their doctors for a full understand of the current findings.
Fenretinide
ReVision Therapeutics’ Phase 2 trials have been completed with a surprising outcome. In addition to expected positive results, researchers have found that the drug fenretinide, taken orally once a day, also reduces by 2.2-fold the rate of conversion to neovascularization (hemorrhaging) in patients with geographic atrophy (end stage dry AMD). This means that fenretinide, in addition to slowing the progression of dry AMD, could also become a pre-treatment for wet AMD, a condition that is responsible for 85-90% of AMD related vision loss.
As a result of these findings, the scientists hope to move forward to a larger phase 3 clinical trial to evaluate this therapeutic effect in a larger patient population.
Lucentis “Super Dose”
Genentech’s HARBOR trial has revealed that a higher dose of Lucentis (ranibizumab) for treatment of wet AMD has been found to be more effective in fifty “incomplete responders” over 24 months. “Incomplete responders” are individuals who have shown no appreciable response to the normal treatment. Intravitreal injection with 2.0 mg, however, rather than the current 0.5 mg, led to a significant decrease in retinal thickness (swelling) after the first 3 months, plus a 4-letter gain after 8 weeks. This improvement was maintained up to one year with no serious adverse events.
AL-8309
Alcon Pharmaceuticals Company is developing a topical drug, AL-8309, which, when given one to two times daily has been shown to block the inflammatory response in rodent retinas exposed to blue light. Since inflammation is thought to be a contributor to development of AMD, and since AL-8309 inhibits the complement system that initiates inflammation, the drug is showing promise as a potentially effective treatment for dry AMD.
VEGF Trap-Eye
Regeneron Pharmaceuticals, Inc. and Bayer Health Care, have entered phase 3 trials comparing the anti-angiogenic drug, VEGF Trap-Eye, with Lucentis for treatment of wet AMD, central retinal vein occlusion (CRVO), and diabetic macular edema (DME). The drug is expected to improve patients’ visual acuity over time without the need for monthly intravitreal injections.
In the Phase 3 GALILEO study, patients with CRVO received six monthly injections of either VEGF Trap-Eye at a dose of 2mg or sham injections. At the primary endpoint patients gained 15 letters of vision from baseline. At a secondary endpoint they gained, on average, 18 letters of vision. These early findings showed that VEGF Trap-Eye has the potential to provide patients and physicians a new treatment option for central retinal vein occlusion.
Regeneron is now seeking marketing approval for treatment of CRVO in the United States. Bayer HealthCare is planning to submit regulatory applications in Europe in 2012.
Lucentis
The current treatment protocol is recognized by the company as a burden on patients. Researchers are, therefore, working on ways to improve the delivery method. One possibility is reduction of frequency of injections.
Practitioners are finding that not all patients are responding as expected with Lucentis. About 10% of patients have actually lost 2-3 lines of acuity after treatment. To address this issue, the new DAWN study will identify ahead of time, by means of a blood test, how well a patient will respond to the drug. Treatment could then be adjusted for best benefit. Genentech scientists are also looking at potential genetic causes for those patients who are not responsive to Lucentis.
As a side note, Novartis Pharmaceuticals Corporation is initiating a 5-year patient management study (LUMINOUS) to gain further understanding of long-term effectiveness of Lucentis, treatment patterns, long term safety, and health-related quality of life issues. The study was launched in 34 countries in March 2011.
NT-501
Another drug, NT-501, developed by Neurotech, is a treatment designed to protect, and in some cases rescue, dying photoreceptors in the retina in order to preserve vision. This treatment relies on a growth factor produced by the human body called neurotrophic factor (CNTF). Human cells engineered to produce CNTF are implanted in the eye in a tiny specially designed capsule which protects these cells from the patient’s immune system and continually releases a small amount of the growth factor. Neurotech has announced that this so-called encapsulated cell technology (ECT) has completed Phase 3 trials with good results.
There have been no serious ill effects associated with the treatment or with having the capsule implanted. NT-501 is also being tested as a treatment for other retinal degenerative disorders including retinitis pigmentosa.
New Treatment Possible for Dry AMD
A new study published in the February 2011 journal Nature reports that dysfunction of an enzyme called DICER1 may be a cause of geographic atrophy (dry AMD). Researchers at the University of Kentucky found that levels of the enzyme are higher in healthy retinas than in eyes affected by AMD. They demonstrated that low DICER1 levels lead to buildup of a toxic genetic material called alu, This, in turn, causes geographic atrophy (dry AMD).
Two treatments may potentially halt the progression of the disease: one which boosts levels of the enzyme, and the other which breaks down the toxic Alu RNA. To test the hypothesis, the University of Kentucky is planning to start human trials by the end of 2011.
SURGERY
Human Retinal Cells Developed From Non-embryonic Stem Cells
On March 24, 2011, Georgetown University Medical Center reported in the journal “Stem Cells” that their researchers have, for the first time, produced retinal cells from human induced pluripotent stem (hiPS) cells, rather than embryonic stem cells. hiPS cells are derived from the patient’s own body, thus bypassing the moral issue of using human embryos.
This is an important step in the research, but several viability and safety issues still need attention before hiPS cells can be introduced into humans.
Microplasmin for vitreal adhesion
A single intravitreal injection of a new drug called microplasmin has been shown in Thrombogenics’ Phase 3 trials to relieve adhesion of the vitreous (the gel that fills the inside of the eye) to the inside of the retina. This reduces risk of damage from the tugging of the vitreous on the retina, which can lead to such conditions as diabetic vitreous hemorrhage and macular hole. It accomplishes this by inducing a gentle post vitreous detachment (PVD), and that can help eliminate the need for surgery to remove the vitreous from the eye.
Implantable Miniature Telescope Approved
VisionCare Ophthalmic Technologies, Inc. announced on July 6 that the FDA approved the company’s Implantable Miniature Telescope to improve vision in patients with end-stage AMD.
The telescope implant is designed to improve visual acuity. The magnification provided by the implant reduces the impact of the blind spot caused by end-stage AMD.
VisionCare will conduct a post-approval study to monitor patient outcomes under commercial conditions. A second smaller study will follow clinical trial patients for an additional two years.
VisionCare is submitting an application to the Centers of Medicare and Medicaid Services for a new code to establish Medicare beneficiary access to this implantation procedure. For more information about the telescope implant and related treatment program, see www.centrasight.com.
Radiation Therapy Continues To Show Promise
In October, NeoVista made public the company’s one-year results from the preliminary study MERITAGE-I. The study was designed to examine their radiation procedure (epimacular brachytherapy) for patients undergoing chronic therapy with anti-VEGF agents for wet AMD. Study results showed that a single radiation treatment stabilized visual acuity in 79% of this patient population, while decreasing the number of anti-VEGF injections required. Most importantly, 47% of patients enrolled in the study experienced some improvement in their visual acuity, while 10% of patients gained 15 or more letters of visual acuity at 12 months.
The study results also pointed to a favorable trend with respect to a reduced number of anti-VEGF injections following delivery of radiation versus the period of time leading up to the intervention. In addition, 25% of patients remained injection-free at 12 months following the procedure.
NUTRITION
AREDS2
The National Eye Institute’s second Age-Related Eye Disease Study (AREDS2) is continuing. The original AREDS formula was approved in 1998. This time, subjects are being given a slightly altered formula containing the original vitamin dosages minus beta-carotene, a lower dosage of zinc, and addition of lutein, zeaxanthin and omega-3. The purpose is to see if the revised formula will help even more to slow the progression of AMD to the advanced stages. The new study began in June 2008, and results are expected in the year 2013. Meanwhile, many nutriceutical companies have gone ahead and updated their products to reflect the more current research. It is advisable to discuss with all of your professional care providers any additions or changes in your diet or supplementation.
TECHNOLOGY
iPad2
The most common complaint about low vision technology is the high price of assistive devices. With government assistance available only to veterans, many people simply cannot afford to purchase the products that can make their lives so much easier. With this year’s introduction of Apple’s new iPad 2, however, that has almost become a non-issue.
For less than half the cost of most electronic magnifiers, visually impaired people can now own virtually every low vision gadget all wrapped up in a device no larger than a thin book. The iPad2 can read to you in 21 languages, magnify images and text, tell you what color your shirt is, guide you across town, magnify the face of your grandchild, call a friend, shop online, manage your finances, identify currency, help you type a letter, read Braille, tell the date and time, and so much more. And it can all be done using tactile buttons or touch screen controls. Apple also offers a year of personal training on the iPad2 for $99.
This has set the standard, and we can now expect more advances at even lower prices to come our way. And if that doesn’t brighten your day, read on:
Driving Blind
The National Federation of the Blind announced on January 29, 2011 that, for the first time, a blind individual has driven a street vehicle in public without the assistance of a sighted person.
The car was equipped with laser range-finding sensors that conveyed information to a computer inside the vehicle, allowing it to create and constantly update a three-dimensional map of the road environment. The computer sent directions to vibrating gloves on the driver’s hands, indicating which way to steer, and to a vibrating strip on which he was seated, indicating when to speed up, slow down, or stop.
Also this past year, Google revealed it’s own version of what they call an autonomous vehicle. The company has been working in secret on vehicles that can drive themselves.
According to the New York Times, seven Google test cars have driven 1,000 miles without human intervention and more than 140,000 miles with only occasional human control. One even drove itself down Lombard Street in San Francisco, one of the steepest and curviest streets in the nation. The only accident, engineers said, was when one Google car was rear-ended while stopped at a traffic light.
They say this technology may be available to the public in eight years. If that happens, one of the thorniest problems of low vision, transportation, will no longer be an issue.
AMD Numbers Continue to Fall
“The number of Americans with macular degeneration fell 30 percent in about two decades,” according to a study published in the January issue of the Archives of Ophthalmology, “reducing the threat from the leading cause of [visual impairment] among the elderly.”
The study authors explained that “Reductions in smoking and blood pressure, key risks for the condition, and increased use of antioxidant vitamins that keep the disease at bay may account for the decline”. The study also revealed that the rate of advanced AMD among all the participants was 0.8 percent, and that AMD affects approximately 6.5% of adults ages 40 and over, compared with the previous estimate of 9.4%.
Data was obtained from 7,081 people, aged 40 and older, who took part in the 2005 to 2008 National Health and Nutrition Examination Survey.
Other research has been confirming this trend. In 2007, a 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. 2,968 participants with early AMD and 3,588 participants with late stage AMD were examined at 5-year intervals between 1988 and 2005 as part of the Beaver Dam Eye Study.
Then, in 2010, a study reported to the Association for Research in Vision and Ophthalmology showed a 68% lower incidence of macular degeneration in the Baby Boom population. That research suggested 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.
The results of this research further emphasize the importance of environmental and lifestyle factors to retinal health.
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This wraps up my summary for this year. I hope you will share this information with your family, friends, and doctors. You are in a position to help others understand, and by doing so, you will be serving a valuable purpose. Thank you for your help!

Summary of Research and Developments in Macular Degeneration: 2008-2009

by Dan Roberts
June 11, 2009
Laser Rejuvenates the Retina

According to a study announced at the Euretina Congress in May 2008, a laser treatment that “cleans up” Bruch’s membrane may slow down the progression to AMD.
Bruch’s membrane is the tissue that separates the photoreceptor cells (our sight cells) from the nourishing blood vessel layer of the retina. It is through Bruch’s
membrane that the nourishment passes. As we age, however, the membrane can become clogged with debris, inhibiting the process and leading to cell malnutrition. Research at St. Thomas’s Hospital in London has resulted in development of a
therapeutic approach to the problem. The Retinal Rejuvenation Therapy (2RT, Ellex) uses a special green nanosecond pulse laser for “reconditioning” Bruch’s membrane and photo-regeneration. Improvement in visual function has been noted in
humans during preliminary studies. Now, under the guidance of
John Marshall, Ph.D., researchers are setting up a trial to treat the yet-unaffected second eyes of patients who have already lost vision in one eye due to neovascular problems.
The ultimate goal, said Dr. Marshall, is to treat patients in their 40s to keep their eyes young and prevent age-related degenerations of the retina. The treatment is noninvasive and seems to have no adverse effects on the photoreceptors or other parts of the eye.
Good Visual Outcome Following Cataract Surgery

A new study (Nature, Aug 2008) has found good visual outcome following cataract surgery in patients aged 90 and older. The study compared visual outcome of patients with macular degeneration, glaucoma and various other ocular conditions.
Overall visual acuity improvement was 68%, whereas unchanged and worsening rates were 16% each. Results showed that AMD patients showed less improvement than patients with glaucoma or with no visual problems.
The researchers concluded that approximately 70% of very elderly patients can achieve visual acuity improvement following cataract surgery, which rises to 82% in those without accompanying problems. Although patients with AMD show less improvement, 62.5% can still enjoy improvement in visual acuity.
Cataract Surgery Appears Safe

More recent studies, however, are disputing that finding, starting with a report in 2005 that patients who had cataract surgery did not have a higher risk of progressing to more advanced forms of macular degeneration when compared to those who did not have cataract surgery.
This was supported by research published in the February 2009 issue of the Journal of Ophthalmology. Led by Emily Chew, MD (also involved in the 2005 study), the team reported that, after reviewing 11 years of patient follow-up data from the large Age-Related Eye Disease Study (AREDS), “The frequency of neovascular age-related macular degeneration, geographic atrophy, and central geographic atrophy did not differ between patients who had cataract surgery and those who did not. . . [This] may provide some reassurance to patients with age-related macular degeneration who are considering cataract surgery.”
A large comprehensive cohort study reported by J.J. Wang to the 2009 ARVO meeting also confirmed previous studies in finding no significant increased incidence of AMD in eyes having undergone cataract surgery. Dr. Wang stressed, however, that here may be an increase in combination with other AMD risk factors.
New Drug May Reduce Number of Injections for Wet AMD
Regeneron Pharmaceuticals, Inc. and Bayer HealthCare AG Have announced that patients with wet AMD receiving VEGF Trap-Eye in a Phase 2 extension study on an “as needed” dosing schedule continued to show highly significant improvements in retinal thickness and vision gain at 52 weeks. During weeks 12 to 52, patients from all dose groups combined received, on average, only two additional injections. This supports Regeneron’s expectation that, with VEGF-Trap-Eye treatment, patients’ visual acuity will improve over time without the need for monthly intravitreal injections.
Zinthionein in Trials for Treatment of Dry AMD

Zinc has been shown to be an effective antioxidant, which is beneficial to the retina. In July 2008, researchers at Pipex Pharmaceuticals announced success with a complex that evidently results in a more potent antioxidant than zinc alone. This “zincmonocysteine” molecule was developed by combining L-cysteine and zinc in a ratio of 1:1.
Under the commercial name Zinthionein, it was then administered as a 25 mg oral capsule twice a day to 80 test subjects for a period of six months. According to the
phase 2 study results (David Newsome, primary investigator), these patients demonstrated a highly statistically significant improvement in visual acuity, contrast sensitivity and photorecovery time. Continued success in the trials could lead to a new and effective therapy for dry AMD.
More info: www.adeonapharma.com
New Dry AMD Gene Found

As reported in the Aug. 28 online edition of the New England Journal of Medicine, researchers have found a genetic link associated with dry AMD. That’s the good news. The bad news is that siRNA drug therapy may increase the risk for dry AMD in patients who have that genetic variant.
The research team found that the protein TLR3 helps fend off certain viral infections. However, it also increases the risk for dry AMD in subjects taking an experimental anti-VEGF drug called “small interference ribonucleic acid” (siRNA),
which activates TLR3. In fending off viral infections, TLR3 also attacks infected retinal cells, resulting in “a 60 percent spike in retinal cell death among mice and humans
genetically susceptible to developing dry AMD.”
Patients currently involved in the siRNA study (labeled Cand5) sponsored by Acuity Pharmaceuticals should contact their doctors for more information.
“Low Luminance Deficit” May Predict More Severe Vision Loss

It appears that, of people with advanced dry AMD (geographic atrophy) who have a corrected visual acuity of 20/50 or better, those who test more poorly in dim light may progress sooner to more severe vision loss.
A research team under the direction of MD Support advisor Janet Sunness, M.D. (Hoover Services for Low Vision and Blindness, Greater Baltimore Medical Center), found that visual dysfunction under low light can predict subsequent visual acuity loss in late-stage AMD patients.
Of subjects with a visual acuity of 20/50 or more, those who had the worst “low luminance deficit” at the beginning of the study showed a significantly greater loss of visual acuity at two years. 40% of this group showed a loss of three or more lines on the acuity test chart. Identification of this risk factor may provide an important means of predicting the rate of vision loss in patients with advanced dry AMD.
Brain Reorganizes to Adjust for Loss of Vision

A new study from Georgia Tech shows that when patients with macular degeneration focus on using another part of their retina to compensate for their loss of central vision, their brain seems to compensate by reorganizing its neural
connections. The study appears in the December edition of the journal Restorative Neurology and Neuroscience.
Eric Schumacher, assistant professor in Georgia Tech’s School of Psychology, said, “Our results show that the patient’s behavior may be critical to get the brain to reorganize in response to disease. It’s not enough to lose input to a brain region for that region to reorganize; the change in the patient’s behavior also matters.”
In this case, that change of behavior comes when patients with AMD make up for this loss by focusing with other parts of their visual field.
Schumacher and his research team found that when patients visually stimulated the preferred retinal locations, they increased brain activity in the same parts of the visual cortex that are normally activated when healthy patients focused on objects in their central visual field. They concluded that the brain had reorganized itself.
While there is evidence with other tasks that suggests that the brain can reorganize itself, this is the first study to directly show that this reorganization in patients with retinal disease is related to patient behavior. The research group is currently studying how long this reorganization takes
and whether it can be fostered through low-vision training in eccentric viewing.
The Latest on AREDS

Emily Chew, M.D., reported to the ARVO meeting that genotypes determine the extent of protection offered by the AREDS formula. In the ARED study, people with genotype TT showed the greatest protective effect, while those with genotype CC
showed the greatest risk of progression to advanced geographic atrophy.
Dr. Chew said that patients can probably discontinue the AREDS supplements once the advanced wet stage is reached. Patients with non-central geographic atrophy (dry MD) and no choroidal neovascularization (vessel growth and leakage) should continue.
Finally, Dr. Chew on the new AREDS2 study. This is a followup to the original “Age-Related Eye Disease Study” completed in 1998. That study resulted in most doctors recommending the AREDS formula to patients in the intermediate stage of
AMD, in order to slow progression to the advanced stage. The formula contains vitamin C, 500 mg; vitamin E, 400 IU; beta carotene, 15 mg; and zinc, 80 mg. The new formula now being tested is slightly altered, with less zinc, no beta-carotene, and the addition of lutein, zeaxanthin and omega-3 fatty acids DHA and EPA. The purpose is to see if the new formula will be even more effective. The AREDS2 cohort has been fully recruited, and first results are expected in 5 years.
PDT Still a Viable Treatment in Some Cases

Several years ago, photodynamic therapy (PDT) was the most effective treatment for wet AMD, but it has been mostly replaced by the new antiangiogenic drugs. This treatment involved injection of the light-activated drug Verteporfin (Visudyne) into a vein, followed by targeting the leaking blood vessel with a low power laser. This destroyed the vessel and stopped the leakage, but it also caused some residual
damage to surrounding cells after repeated procedures. Still, PDT is used in some cases where the vessel’s location is not close to the center of the macula and quick action is necessary.
Now, a new less damaging and more effective approach called “Targeted” Photodynamic Therapy (TPT) is being studied. According to Dr. R.A. Adelman in a report to the ARVO meeting, a protein called Factor VII is conjugated with Verteporfin.
Intravitreal injection of the compound in a rat model with choroidal neovascularization showed efficacy at 1/10th the usual dose of Verteporfin and 3x better visual function
after lasering. This proved to be more effective and safer for surrounding cells than standard PDT at a significantly lower dose.
The Latest on Lucentis

Lucentis, developed by Genentech Pharmaceuticals, is one of two FDA approved drugs used in treatment of wet AMD. The other is Macugen, which has been shown to be less effective. Avastin is also being used off-label with reported success, but it has
yet to be shown to be safe and efficacious in large studies.
Three followup studies of Lucentis, called HORIZON, EXCITE and SUSTAIN, were reported on at the ARVO meeting by Drs. M. Singer, C. Simader and F.G. Holz.
The HORIZON study, which ended in Sep 2008, followed Genentech’s Marina, Anchor and Focus trials, all of which were followup studies of Lucentis. The results showed that the rate of ocular and nonocular adverse events was low, repeated
injections were well tolerated after 4 years, and delay in initial treatment resulted in a higher loss of vision.
The EXCITE study compared quarterly treatment with monthly treatment using Lucentis. Best corrected visual acuity and retinal morphology were found to be better with a monthly regimen of injections.
The SUSTAIN study analyzed safety of monthly dosages of 0.3 and 0.5 mg. Lucentis was found to be safe and effective, no matter what the amount of dosage or the interval of time between treatments.
Since monthly treatment on an as-needed basis at 0.5 mg has been found to be most effective, more refined testing (eg. higher resolution OCT) will be needed in order to better judge if and when patients need to be retreated.
Bilateral Injections Appear Safe

Dr. KariAnne Galler reported to the ARVO meeting that there is no particular increase in risk for patients with bilateral macular degeneration treated with bilateral injections
of anti-VEGF drugs. Also, there is a strong patient preference for the ease and convenience of having bilateral rather than unilateral injections.
Obama Lifts Limits on Stem Cell Research

President Obama has lifted the Bush administration’s limits on human embryonic stem cell research. Mr. Obama announced the decision on March 9, saying he hoped Congress would follow with bipartisan legislation that would ease the existing restrictions even more.
The president acknowledged that studying stem cells extracted from human embryos is deeply divisive, but he said the majority of Americans “have come to a consensus that we should pursue this research; that the potential it offers is great,
and with proper guidelines and strict oversight the perils can be avoided.”
First Human Embryonic Stem Cell Study Approved By FDA

Geron, a biotech company, has announced that the federal government will allow the world’s first test in people of a therapy derived from human embryonic stem cells. Until now, federal financing for research on embryonic stem cells has been restricted, because creation of the cells entails the destruction of human embryos.
The intended reversal of this policy by the newly-elected administration may or may not have influenced this recent decision.
Geron will enroll paralyzed patients who can be treated within 2 weeks of their injury. The subjects will then be evaluated for at least one year, after which the company hopes to increase the dose and expand the number of participants.
This release of government funding is expected to set a precedent for more stem cell research in the low vision field. For more information about the research to this point, see “The First Seven Years: An Overview of Stem Cell Transplantation Research for Treatment of Retinal Disease” on this site.
Stem Cell Therapy Presents Challenges

A special interest group discussed the challenges of bringing stem cell therapy to the patients. The topics were addressed by P.J. Coffey (Institute of Ophthalmology, University College, London), H. Klassen (Univ. of California, Irvine), and M. Friedlander (Scripps Research Institute).
The topics of discussion were:

  • Ways of getting the cells to the site of action, either by surgical insertion or injection into the vitreous fluid.
  • The safety of the procedure
  • The length of time it will take for the procedure to have an effect
  • The question of whether the body will reject the implants
  • Sources of stem cells

To summarize:
Dr. Coffey stated that the goal of The London Project at Moorfields Hospital is to reconstruct the macula by repopulating the retinal pigment epithelium (RPE) to nourish the photoreceptors. This has been accomplished successfully by macular translocation and RPE transplantation. The problem, however, is that these procedures take several hours and at least two separate visits to the clinic. The solution, said Dr. Coffey, is to implant (by injection) a permanent artificial membrane of human embryonic cells. This has been shown to stop pig photoreceptors from dying, and there has been no immunological response (i.e. rejection) so far.
Dr. Klassen discussed culture and transplantation of retinal progenitor cells (RPC), which he says is a key developmental stage in the pathway to replicating rod photoreceptors, even for Müller and ciliary cells. RPCs have been obtained from
animals and encouraged (by adding a growth factor) to differentiate into photoreceptors. They have been well-tolerated in the treated retinas. He added that human RPCs have been successfully used in China to repair the optic nerve.
Dr. Friedlander discussed adult stem cell based therapies. Sources for such cells are the cornea, bone marrow, peripheral blood, spinal cord blood, skin, hair and dormant stem cells. He introduced a new strategy involving rebuilding retinal vessels instead of inhibiting neovascularization. He described how this “vasculotrophic rescue” can be done with bone marrow derived stem cells.
FDA Panel Recommends Approval of IMT

On March 27, 2009, the FDA’s ophthalmic device panel recommended approval of Vision Care Ophthalmic Technology’s implantable miniature telescope (IMT) for patients with advanced stage AMD. After 5 years of trials and a prior unsuccessful submission to the panel, the IMT has now met all requirements for safety and efficacy.
The FDA usually follows the recommendations of an advisory panel, but is not required to do so. The panel recommended approval of the device with conditions including post-approval surveillance and labeling suggestions. The panel decision
was reached by a vote of 8 to 0.
Allen W. Hill, CEO of VisionCare, said “We are pleased with the panel’s recommendation for approval and will work closely with FDA to address the approval conditions. We look forward to providing the ophthalmic community a new treatment option to improve vision and quality of life for patients with untreatable, end-stage agerelated macular degeneration.”
I spoke to the panel shortly before the vote. I told them that, until now, nothing has offered long-term vision restoration for people in the advanced stage of the disease.
That stage has traditionally been one of transition to nonvisual skills such as cane use and Braille. With the IMT, it may be possible for some of us to put that off indefinitely, and that gives us one more cannon to fire.
For more information on the research, visit VisionCare’s website at www.visioncareinc.net or call (408) 872-0526.
Seeing With Your Tongue

One of the most interesting developments reported at Vision 2008 in Montreal was new device called BrainPort, which (according to the abstract) enables perception of visual information using the tongue and camera imaging system as a paired substitute for the eye.
Visual information is collected from a head mounted image sensor and translated into electrical patterns displayed on the surface of the tongue. The system has tested favorably on subjects with no vision, and it is now being adapted to assist individuals with macular degeneration and related diseases.
The long term goal is to develop a fully portable, unobtrusive
device that will track with the userís gaze point, capture information centered in the area of vision loss, and display the information on the tongue. This device will “fill in”
the area of vision loss, will be compatible with other vision-assisting devices, will not be surgically invasive, and will be easily customizable and upgradeable. Developers are hoping to have the BrainPort commercially available within 2
years. Here is where you can read more about it:
vision.wicab.com/technology
DIET & NUTRITION
Statins May Hasten Onset of Wet AMD

What effect do cholesterol-lowering drugs have on the retina? A pilot study in 2006 found “that treatment with simvastatin increased blood-flow velocity in the retinal arteries and veins and decreased intraocular pressure. (Nagaoka T et al. Arch Ophthalmol 2006; 124:665-670.)
This study supports the thinking that increased blood flow is generally beneficial to the retina. Recent research, however, has shown that taking statins to lower cholesterol levels might hasten the onset of wet AMD in people who are already
affected by the dry form. The abstract for this study may be read on the Web at www.tinyurl.com/5ksj6a.
Considering the proven beneficial effects of drugs like simvastatin for people with circulatory problems and high cholesterol, it would be wise to keep this information in mind, but it would not be wise to stop taking them altogether without professional consultation. Until researchers have sorted out the facts, a patient’s decision should be based upon individual circumstances and discussed with professional care providers.
Vitamin C May Lower Statin Levels

A UC Berkeley study, led by Gladys Block, PhD, suggests that 1,000 mg of daily supplemental vitamin C can lower concentrations of C-reactive protein (CRP), the marker associated with systemic inflammation. (Free Radical Biology and Medicine, Jan. 1, 2009). It suggests that a daily dose of supplemental vitamin C can lower CRP levels in healthy, non-smoking adults in two months.
Gladys Block and her staff found that for people with elevated CRP levels, the amount of CRP reduction achieved by taking vitamin C in this particular study is comparable to that in many statin studies.
A multinational clinical trial led by researchers at Harvard Medical School (the Jupiter Trial), found that among people who had high levels of CRP at baseline, levels of CRP were 37 percent lower in the subjects who took statins compared to those who took the placebo.
In the UC Berkeley study on vitamin C, participants who started out with CRP levels greater than 2 milligrams per liter had 34 percent lower levels of CRP with vitamin C compared with a placebo after two months.
“This is clearly a line of research worth pursuing,” said Dr. Block. “It has recently been suggested by some researchers that people with elevated CRP should be put on statins as a preventive measure. For people who have elevated CRP but not elevated LDL cholesterol, our data suggest that vitamin C should be investigated as an alternative to statins, or as something to be used to delay the time when statin use
becomes necessary.”
The benefits to the consumer are that Vitamin C is considerably less costly, and it does not carry the risk of serious side-effects associated with statins.
Source: Ellen Troyer, MT, MA (Chief Research Officer, Biosyntrx .com
Excess Weight Contributes to Mortality

by Ellen Troyer, MT MA
Biosyntrx Chief Research Officer
Excess weight is an epidemic in the United States. There is strong scientific agreement that excess weight (BMI over 25) contributes to overall mortality. It also significantly increases the risk of serious degenerative diseases, including cataracts, macular degeneration, glaucoma, and diabetic retinopathy.
The National Center for Health Statistics estimates that 65% of the U.S. population is overweight, with 34% of the population being clinically obese. Scientists have also identified the significantly increased risks associated with excess weight for 20 other diseases or conditions. According to the U.S. Surgeon General report, excess weight and obesity are responsible for 300,000 deaths every year in the U.S.
Vitamins B-6, B-12 and Folic Acid May Protect Against AMD

Ellen Troyer, MT MA
Biosyntrx Chief Research Officer
A recent study suggests that a combination of vitamin B-6, vitamin B-12 and folic acid may protect women against age-related macular degeneration. Epidemiologists at Harvard Medical School and Women’s Hospital in Boston analyzed data collected as part of a large trial originally designed to test the effects of other vitamins on women with heart problems. All subjects were permitted to take multivitamins with B-6, B-12 and folate up to, but not exceeding, recommended
daily allowances (RDAs). Those getting the B-6, B-12 and folate supplements received much larger amounts.
After 7.3 years, researchers found 82 cases of age-related macular degeneration among women taking placebos and only 55 cases in the women receiving the high-potency B vitamin supplements. While an explanation for the apparent protection from macular degeneration remains unknown, it is known that folate, B-6 and B-12 can drive down blood concentrations of homocysteine, a methionine metabolism by-product compound
suspected of damaging blood vessels.
On the surface this study seems to be very positive, but it raises some concerns about the folic acid dosage. Excessive supplemental folic acid can mask or obscure fairly common vitamin B-12 deficiencies in older people. This can result in an increased risk of progressive, unrecognized neurological damage. Dosage of supplemental folic acid over 1 mg per day has also been associated with impaired gastrointestinal absorption of zinc in some cases.
It’s good to remember that more is not always better.
Too Much Red Meat?

Research* has revealed that a diet high in red meat may increase one’s risk of developing AMD, while consumption of chicken may lower the risk.
Researchers followed 6,734 persons aged 58-69 years, from 1990 through 2006. Final data showed that higher red meat intake was positively associated with early AMD. The odds ratio for consumption of red meat 10 or more times a week versus less than 5 times a week was 1.47. Conversely, consumption of chicken 3.5 or more times a week versus less than 1.5 times a week was inversely associated with late AMD. The team concluded that different meats may differently affect AMD risk and may be a target for lifestyle modification.
Inflammation is being identified as the main culprit in the development of AMD, and cholesterol is inflammation’s “partner in crime.” Fatty red meat is a major source of cholesterol, while lean red meat actually produces less than the body does by itself.
High quantities of red meat, therefore, may be an important risk factor, but it appears that we can sidestep the problem by consuming less, and only the leanest cuts.
*Red Meat and Chicken Consumption and Its Association With Age-related Macular Degeneration, Elaine W.-T. Chong, et al (American Journal of Epidemiology, November 25, 2008).
Occurrence of AMD Declining

A new study reports 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.
The 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.
The investigators cannot yet explain the results. Improvements in health care and lifestyle over the previous 15 years do not explain the decline, but other factors might. These include other exposures earlier in life (e.g., infectious disease
outbreaks such as the flu pandemic of 1918), dietary restrictions specific to a period (e.g., the Great Depression), or other unmeasured factors.
Personally, I would like to think that greater health conciousness and awareness of the risk factors for AMD have made a positive contribution. We can play a part in maintaining that decline by continuing to educate ourselves and others about how we may fend off this disease, at least until these promising cures we hear about reach our hospitals and clinics.
Thank you for reading this summary. The fact that it has been lengthy is testament to the encouraging work being done in the field, and let’s continue to remain positive about the positive outcomes, whether for our benefit or for the benefit
of those who follow us.