Summary of Research and Development — 2018

Transcript of a presentation to the International Low Vision Support Group
June 2018
Dan Roberts, Director
Select this link for audio-visual format
This is our 13th annual summary of leading research and developments occuring during the past 12 months in the fields of blindness and low vision.
Sources for further information will appear beneath each topic heading. References are listed by date of publication in the “News & Info” section at More information about each topic, along with sources, may be found there.
This year’s summary will offer brief descriptions of work done in the categories of:

  • discontinued and delayed trials
  • updates on continuing trials 
  • gene therapy
  • combination therapies
  • surgical interventions
  • nutrition
  • stem cells
  • daily living
  • new technology
  • the future

I like to report good news, but sometimes bad news needs to be shared, as well, so let’s get that out of the way first. This past year has seen unexpected negative findings from three promising clinical trials.
Genentech announced in September that the primary endpoint was not met by the drug lampalizumab, a treatment for advanced dry macular degeneration (geographic atrophy). It was designed to inhibit inflammation, but the results showed it to be less effective than hoped.
Lampalizumab for Dry AMD Unable to Meet Expectations in Phase III Trial (9/9/17)
Another disappointment was the drug nesvacumab (REGN910), which was being tested in combination with Regeneron’s Eylea as a potential treatment for wet macular degeneration. Regeneron reported in November that the results were insufficient to warrant Phase 3 development. 
Regeneron Study of Nesvacumab Discontinued (11/27/17)
Iluvian, a corticosteroid implant devised by Alimera Sciences, had demonstrated effectiveness in the treatment of neovascular diabetic retinopathy without the need for monthly injections. Early results were very encouraging, but concerns by the FDA about safety and manufacturing standards have slowed its progress toward clinical trials.
Iluvian Continues to Show Good Results in DME Trials (12/6/17)
Such news may be disappointing, but we must remember that there is no such thing as failure in science. It is just as important to learn what doesn’t work as well as what does, and valuable lessons are beng learned from these discontinued trials. 
On the positive side of the news, several drugs we discussed in our 2017 summary are still in trials and continuing to show promise. The focus of much of the research is now on methods of improving current treatments and reducing the burden on patients by prolonging the time between clinic visits.
A topical eye drop, PAN-90806, for the treatment of wet AMD, diabetic retinopathy, and potentially diabetic macular edema (DME). Panoptica, the developer, has reported that the monotherapy shows promise as an alternative to injections, and they are hoping to begin trials this year.
Eye Drops for Wet AMD Showing Positive Results (11/22, 2016)
Emixustat, a drug designed to slow the progression of macular atrophy, has completed Phase 2 trials for evaluation of safety and tolerability in patients with Stargardt disease, diabetic retinopahy, and dry macular degeneration. Results from this phase have not yet been reported.
Trials beginning for Emixustat Treatment of Stargardt Disease (1/27/17)
Apellis Pharmaceuticals has finalized the trial design for its planned Phase 3 program evaluating APL-2 for the treatment of patients with geographic atrophy (the advanced stage of dry macular degeneration).The Phase 3 program, planned to begin later this year, will consist of two identical studies to assess the efficacy and safety of multiple injections of APL-2 in the eyes of patients with GA. The Phase 3 trials will be substantially similar in design to the Phase 2 trial, which, at 12 months, showed as much as a 29% reduction in damage to the retina. 
Promising Update on APL-2 for Dry AMD (8/25/17)
Alternative drug delivery
Several alternative methods are still underway for delivering drugs to the retina in cases of blood vessel growth and leakage. These are a refillable port-delivery system and two different time-release capsules, all of which reduce the burden and risk of frequent injections. None of these drug delivery systems have yet been tested in humans, but they all show promise for the near future.
In December, the FDA approved Luxturna, a new gene therapy developed by Spark Therapeutics, to treat an inherited form of vision loss that can result in blindness. Patients with Leber congenital amaurosis, which affects young boys, will be the first beneficiaries of retinal gene therapy, with retinitis pigmentosa and Stargardt disease to follow after further study.
Luxturna, which is injected into the eye, is the first directly administered gene therapy approved in the U.S. that targets a disease caused by mutations in a specific gene–in this case the RPE65 gene. The therapy is expected to be available in selected centers this year, with the price for a single dose set at at $425,000 per eye, or $850,000 per patient.
FDA Approves First Gene Therapy for Inherited Retinal Dystrophy (12/10/17)
A new drug called RGX-314 is being developed as a one-time sub-retinal injection for wet AMD. This would be a significant improvement over current anti-VEGF therapies requiring repetitive and frequent injections. 
REGENXBIO Inc. announced in June 2017 that the first human patient has been dosed in a phase I clinical trial of RGX-314. The drug uses a newly developed gene delivery method that neutralizes VEGF protein leading to formation of new leaky blood vessels in the retina. It has been shown in animal models to increase the time between treatments to as long as one year.
New One-time Gene Therapy For Wet AMD Could Replace Regular Injections (June 1, 2017)
Combination therapies are those which are designed to accompany traditional treatments to improve or prolong results.
Novartis announced in November that their new anti-VEGF drug, brolucizumab, is meeting expectations as a potentially more effective and longer lasting treatment for wet macular degeneration than at least one of the current options. The brolucizumab molecule is smaller than other available wet AMD treatment options, which may allow delivery of a much higher dose and a potentially longer time between injections of up to 12 weeks. The trials are expected to end in 2018, with marketing expected to begin after government approval in 2019.
Brolucizimab May Be the Next Treatment Option for Wet AMD (November 11, 2017)
Since 2005, anti-VEGF drug injections of Lucentis, Eylea, and Avastin have proved effective for treatment of wet AMD and diabetic macular edema (DME). Remember that VEGF is short for vascular endothelial growth factor, which is the substance produced by the body that initiates growth of new blood vessels to carry nourishment to damaged cells. Called neovascularization, this is a valuable healing process built into our bodies, but it is harmful to our retinas. In addition to the original three anti-VEGF drugs designed to block neovascularization, many such therapies have gone into trials, as reported here through the years.
But now, scientists have found a possible counterpart to VEGF called angiopoietin2 (Ang2). It appears that this substance, also produced by the body can, like VEGF, also lead to neovascularization. The researchers are hoping that, by inhibiting the body’s production of Ang2, in combination with current anti-VEGF treatments, the retinal blood vessels can be further stabilized.
Two “anti-Ang2” drugs are being studied for that purpose. RG7716 is being tested in combination with Lucentis, and nesvacumab is being tested in combination with Eylea. Both studies have finished enrollment and are currently in follow-up.
New Anti-Ang2 Drug for Wet AMD Showing Promise (February 14, 2018)
Alongside research to find ways of restoring vision through stem cell therapy and gene therapy, attempts are being made to restore vision electronically by means of bionic implants. In past reports, we have described the ARGUS-2, which has shown success in providing a basic pixelated sense of sight to the totally blind.
In October 2017, Pixium Vision received French authorization to begin a feasibility study in human patients with advanced dry AMD. The company earlier presented information about their newest bionic device called PRIMA–a tiny wireless sub-retinal implant that can provide prosthetic vision at the speed of video, a decided advancement over current imaging.
The initial study was conducted in Paris, and in January the FDA approved a clinical feasibility study of PRIMA implant to be conducted at the University of Pittsburgh Medical Center in 2018.
New Sub-retinal Implant For Dry AMD Entering Trials (April 2018)
First AMD Patient Receives Sub-Retinal Implant (January 2018)
Concerns have been voiced about the risk of cataract surgery for recurrence of neovascularization, and trials have not really assessed the risks. A study was, therefore, designed to determine the risk in patients who had received treatment with anti-VEGF injections for wet AMD. The researchers found that cataract surgery does not appear to increase the recurrence of neovascularization in patients with wet AMD, nor does it have effect on the time to recurrence and on the frequency of anti-VEGF injections required after the surgery.
Recurrence of Choroidal Neovascularization after cataract operation in Age Related Macular Degeneration. Robin D. Hamilton, et al. (ARVO Annual Convention, 2018. Posterboard#: C0030. Abstract Number: 1468 – C0030)
Studies in France and the Netherlands have shown that a Mediterranean diet is linked to a lower risk of age-related macular degeneration (AMD). Researchers investigated the effects of such a diet on a large sample from subjects from two population-based prospective studies. The diet consists of more than median intakes of vegetables, fruits, legumes, cereals, fish, moderate amounts of alcohol consumption and the ratio of monounsaturated to saturated fats and to lower than median intakes of meats and dairy products.
Higher adherence to the Mediterranean diet was associated with a 39% reduced risk of developing advanced AMD. These results highlight that eating a healthy diet such as this may help to limit progression to advanced AMD.
Mediterranean Diet Lowers Risk of AMD (April 2018)
Results from three clinical trials have added support for the use of human embryonic stem cells as treatment for the dry form of age-macular degeneration (AMD). Stem cells injected into the eye appear to have replaced the missing cells damaged by the disease, with no serious side effects. One study suggests it may have even improved vision.
Hadassah-Hebrew University Medical Center in Jerusalem is one of the trial sites, with an additional site for this stem cell treatment expected to open soon in the United States.
A second research group from Bascom Palmer Eye Institute in Miami has conducted two studies for dry AMD and Stargardt disease, the most common form of inherited juvenile AMD. Stem cells implanted in these patients survived for up to three years, with no side effects, and some of these patients even gained vision.
And finally, a new procedure performed at Moreheads has been shown to be a safe and effective method for introducing stem cells into the retina. Implantation of a specially engineered patch of retinal pigment epithelial (RPE) cells derived from stem cells has restored some vision in two people with sight loss from wet age-related macular degeneration (AMD). Researchers hope the new procedure will also help in the future to treat dry AMD and similar diseases of the retina.
The patients were monitored for 12 months and reported improvements to their vision. They went from not being able to read at all to reading 60 to 80 words per minute with normal reading glasses.
Two Trials Take First Step Toward Stem Cell Treatment for AMD (November 16, 2017)
New Stem Cell Therapy Treats Macular Degeneration (March 20, 2018)
Degeneration of photoreceptors (the rod and cone cells) is a leading cause of vision loss. Since there are no effective treatments to restore vision once photoreceptors are lost, photoreceptor regeneration has the very real prospect of alleviating blindness in these eyes.
To that end, a recent innovative study has demonstrated the possibility of reprogramming Müller glia into photoreceptors without passing through an intermediate stem cell state. Previous studies have shown how glial cells can be reprogrammed into different types of neurons in the brain, spinal cord and retina. Now this study aims to highlight a reprogramming technology to convert Müller glia directly into photoreceptors. The technique uses transcription factors to promote reprogramming, an approach that could have a significant effect on the treatment of a wide range of retinal diseases.
Müller Cell Therapy Might Bypass Stem Cell Therapy in Restoration of Sight Cells (April 25, 2018)
A recent observational study at the University of Wisconsin-Madison has found that the risk of developing age-related macular degeneration (AMD) has been dramatically lessening over three generations.
After looking at follow-up data on 4,819 subjects, researchers found that the incidence of AMD has been decreasing by a relative 60 percent for each of the current and past successive two generations. This suggests that aging Baby Boomers (people born between 1946 and 1964) may experience better retinal health longer than did the two previous generations. Whether that will hold true is yet to be seen, but both the Baby Boomer and the new Generation X populations are already seeing comparable declines in AMD incidence. The improvement may be attributed to better environmental conditions, sanitation, nutrition, and approaches to disease prevention.
Incidence of AMD Dramatically Declining (November 2017)
Microsoft has released a free app using amazing new technology to assist blind people. It’s called Seeing AI: Talking camera for the blind.
The app harnesses the power of Artificial Intelligence (AI) to narrate the world around the user by describing nearby people, text and objects. Once it is downloaded, the user simply points the device’s camera at people or scenes, and it will describe them.
Seeing AI can also read barcodes and text aloud. It can help someone who is visually impaired listen to text from a book, describe items on a store shelf, and identify objects.
At this time, Seeing AI is available only for iOS devices and may be downloaded for free from the App Store.
New App for iOS Reads Text and Describes the World (July 15, 2017)
Portable electronic magnifiers have come a long way in the past decade, improving clarity of vision for thousands. A natural development for those who prefer to have their hands free has been the creation of several types of headworn video devices, the leaders in the field being eSight, NuEyes, and IrisVision. These devices are similar in their “smart” technology, but different enough, especially in their price between $3,500 and $10,000, to require diligent decision making.
Headworn Video Devices Are Helping The Visually Impaired To See Better (December 4, 2017)
Advancements in lighting technology for the visually impaired have also made big strides during the past decade. In 2005, companies were touting their new full spectrum (“daylight”) lamps as “healthy for aging eyes”. Patients, and even their doctors, were led to believe that the sun at high noon is the best and brightest light source.
Thanks, however, to a good deal of pushback from researchers and knowledgable consumers, lighting companies have either vacated the low vision market or made welcome adjustments. Realizing that lamps imitating sunlight neither improve the health nor benefit the retina, and realizing that the low vision community is now aware of the potential harm to the eyes of extended exposure to near-UV blue light, safer lamps are now showing up in the stores.
Sadly, full spectrum lamps have not yet disappeared, and their numbers have actually increased to more than 25 different models. These lamps contain such high blue content (over 5000K) that they fool the brain into thinking they are actually brighter than those with cooler color temperatures. When compared side-by-side, however, the differences can be easily seen.
The good news is that about half of those full spectrum lamps are now featuring adjustable color temperature settings. This means that users can choose the heat temperature of lamps they find most comfortable, from “very warm” (around 2800K) to “very cool” (around 6500K), with the safest and best “warm white” somewhere in the middle at 3400K to 4800K). The ability to adjust the heat temperature of a lamp is an acceptable compromise, as long as users apply good judgment.
Another change in the industry has been the switch to LED technology, which enables whiter, brighter, and more economical lighting. These tiny light sources are extremely bright, but the U.S. Department of Energy assures that the proportion of blue emissions by LEDs “is not significantly higher…than it is for any other light source at the same [color temperature].”
The lighting industry is moving in the right direction, but there is still room for improvement in color temperature, brightness control, lamp construction, cost, and truth in advertising.
Low Vision Lighting Technology is Improving (February 3, 2018)
Finally, let’s look at the future. The rate of research and development is moving at an exponential rate, covering many areas of treatment and daily living:

  • Continued refinement of surgical techniques
  • Continued successes with stem cell and gene replacement research
  • Advances in pharmaceutical therapies, including development of biosimilar drugs, which equal the safety and efficacy of current drugs at a lower cost
  • New ways for patients to monitor their own progress at home
  • Development of systems for diagnosis and treatment via the Internet, saving time and money spent for clinical visits
  • Improvements in audibility of assistive devices for those who are both visually and hearing impaired
  • Increased accessibility of portable independent navigation systems for travel both outdoors and indoors
  • Integration of audible speech into assistive devices

We will continue to follow all of this action throughout the coming years and keep you updated with newsletters, email news alerts, and these annual summaries. Knowledge is the best way I know of to keep the fear of the unknown at bay, making living with low vision less stressful, and acceptance a little easier.
Best wishes to everyone for another year of walking this path together!