News

Does VUITY™ Treat AMD?

A new drug called VUITY™ (pilocarpine hydrochloride ophthalmic solution) has recently gained attention as an eye drop that can improve near (close up) vision in individuals over 40. It does not, however, change the condition of the retina. The drug, made by Allergan, works as advertised, but it should not be expected to treat age-related macular degeneration (AMD).

Vuity™ is available by prescription to treat only presbyopia. Presbyopia is common in aging eyes, resulting in stiffening of the eye’s lens and making natural focusing difficult. Reading glasses can help, but eyes with central vision loss from AMD will not benefit from either glasses or Vuity™. Vuity™ works by lessening the size of the eye’s pupil, making it easier to focus on near objects or text. This creates a kind of pinhole effect, which patients may remember as one way doctors test visual acuity. This effect may also be achieved by peering through a pinhole in an index card. 

If in doubt, patients should consult with their doctors for advice about whether Vuity™ will be appropriate for them.

APL-2 (pegcetacoplan) May Soon Become the First Treatment for Geographic Atrophy

Apellis Pharmaceuticals has announced long term results from their Phase 3 DERBY and OAKS clinical studies, testing the efficacy and safety of APL-2 (now called intravitreal pegcetacoplan), as a treatment for geographic atrophy (GA). GA is also known as advanced dry age-related macular degeneration.

In an analysis conducted at month 18 of the clinical studies, treatment with both monthly and every-other-month pegcetacoplan reduced GA lesion growth compared to sham injections (no treatment). Pegcetacoplan continued to demonstrate a favorable safety profile in both studies.

Overall, these longer-term results provide further evidence that pegcetacoplan meaningfully slows disease progression and has the potential to preserve vision longer.

Apellis remains on track to submit a New Drug Application to the U.S. Food and Drug Administration in 2022. This is one of the first steps towards potentially achieving approval for use. They also look forward to working with global regulatory groups to bring forward the first potential treatment for people living with GA.

Pegcetacoplan is the only targeted C3 therapy in Phase 3 clinical trials for GA, a complement-driven eye disease that causes loss of central vision, affects approximately five million people globally and has no approved treatment.

According to SriniVas Sadda, M.D., President & Chief Scientific Officer of the Doheny Eye Institute and lead investigator, “This study provides exciting evidence to support further exploration of the potential of pegcetacoplan for earlier intervention in the course of GA.”

For current information about all major research for treatment of geographic atrophy, see “A Guide to Research in Dry AMD” on this site.

Related earlier articles:

Apellis Entering Phase 3 Trials for Dry Macular Degeneration (2017)

SOURCE: Press Release

Long-awaited Faricimab for wet AMD and DME approved

The FDA has approved Genentech’s Vabysmo (first announced here as faricimab), the only injectable eye medicine approved simultaneously in the U.S. for wet age-related macular degeneration (AMD) and diabetic macular edema (DME).

Vabysmo will be administered using flexible dosing regimens based on patient need. The medication targets and inhibits two disease pathways by neutralizing angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A), which drive the two conditions.

Vabysmo is the first and only FDA-approved injectable eye medicine for wet AMD and DME that improves and maintains vision with treatments from one to four months apart in the first year following four initial monthly doses. Standard of care for wet AMD and DME typically requires eye injections every one to two months.

“Vabysmo represents an important step forward for ophthalmology,” said Charles Wykoff, M.D., Ph.D. (Director of Research, Retina Consultants of Texas in Houston and a Vabysmo Phase III investigator). “With Vabysmo, we now have the opportunity to offer patients a medicine that could improve their vision, potentially lowering treatment burden with fewer injections over time.”

The approval is based on positive results across four Phase III studies in wet AMD and DME. The studies consistently showed that patients treated with Vabysmo given at intervals of up to four months achieved non-inferior vision gains versus Regeneron’s Eylea (aflibercept) given every two months in the first year. Vabysmo was generally well tolerated in all four studies, with a favorable benefit-risk profile.

More information and details about the research may be read here.

SOURCE: Genentech Press Release

Cataract Surgery Shown to Reduce Risk of Dementia

Researchers at Kaiser Permanente Washington have found strong evidence that cataract surgery can lower the risk of developing dementia for up to 10 years in senior adults. The news was reported in the December 6, 2021 issue of JAMA Internal Medicine.

The Adult Changes in Thought (ACT) study of more than 5,000 senior adults showed for the first time that subjects who underwent cataract surgery had nearly a 30% lower risk of developing dementia than those who did not. The study also showed an association between cataract surgery and a lower risk of Alzheimer’s disease. The reason/s for these findings were not reported, but the most reasonable hypothesis is that improved vision quality and light input might benefit the brain—welcome news in light of recent reports showing that dementia from Alzheimer’s disease (AD) is often associated with retinal degeneration. For more information about this, see Retinal Degeneration and Alzheimer’s Disease: An Evolving Link.

SOURCE: “Association Between Cataract Extraction and Development of Dementia” by Cecilia S. Lee, MD et al, 6 December 2021, JAMA Internal Medicine. DOI: 10.1001/jamainternmed.2021.699

Prevent Blindness Launches New Awareness Initiative to Educate Public About Geographic Atrophy

Prevent Blindness has launched its first-ever Geographic Atrophy (GA) Awareness Week from December 6-12, 2021. GA is an advanced form of dry age-related macular degeneration (commonly referred to as AMD) which leads to vision loss in the center of one’s vision. Geographic atrophy results in areas of damaged tissue causing central blind spots. It is estimated that 1 million people in the United States have GA.

Prevent Blindness has created a variety of new resources on geographic atrophy, including a downloadable fact sheet, and a dedicated webpage. A series of shareable social media graphics is also available and will be posted by Prevent Blindness on its various social media channels throughout the week. Development of these new resources was sponsored by Apellis Pharmaceuticals, Inc.

FDA Approves First Biosimilar Drug for Treatment of Wet AMD

The U.S. Food and Drug Administration (FDA) has approved Byooviz (ranibizumab-nuna) as the first biosimilar to Lucentis (ranibizumab injection) for the treatment of wet AMD. Byooviz is also approved to treat macular edema and myopic choroidal neovascularization, a vision-threatening complication of myopia (nearsightedness). The drug is administered by intravitreal injection (delivered into the vitreous humor of the eye) once a month.

Biological products (i.e. Lucentis, Eylea, and Beovu) are generally derived from living organisms and can come from many sources such as bacteria or yeast. A biosimilar is a biological product that is approved based on data showing that it is highly similar to a biological product already approved by the FDA (reference product) and has no clinically meaningful differences in terms of safety, purity and potency (i.e., safety and effectiveness) from the reference product, in addition to meeting other criteria specified by law. Patients can expect the same safety and effectiveness from the biosimilar over the course of treatment as from the reference product.

An important benefit of biosimilars is that they are considerably less expensive. In the case of Byooviz, the savings over Lucentis could be as much as $100 billion in the US over the next 5 years. The FDA granted approval of Byooviz to Samsung Bioepis, and other companies are expected to soon enter the market of biosimilars.

Read about all leading antiangiogenic drugs and current research

SOURCE: Press Release

FDA Approves Genentech’s Susvimo, a First-of-Its-Kind Therapeutic Approach for Wet Age-Related Macular Degeneration (AMD)

Susvimo, previously called Port Delivery System with ranibizumab, is the first wet AMD treatment in 15 years to provide an alternative to standard-of-care eye injections needed as often as once a month. By continuously delivering medicine into the eye through a refillable implant, Susvimo may help people with wet AMD maintain their vision with as few as two treatments per year.

Genentech announced on October 21, 2021 that the U.S. Food and Drug Administration (FDA) approved Susvimo TM (ranibizumab injection) 100 mg/mL for intravitreal use via ocular implant for the treatment of people with wet (neovascular) age-related macular degeneration (AMD). The breakthrough drug delivery system is available to individuals who have previously responded to at least two anti-vascular endothelial growth factor (VEGF) injections. Susvimo, previously called Port Delivery System with ranibizumab, is the first and only FDA-approved treatment for wet AMD that offers as few as two treatments per year.

“Susvimo represents a major advancement in the treatment of retinal disease, and is an important new option for patients with wet AMD,” said Carl Regillo, M.D., Chief of Retina Service at Wills Eye Hospital in Philadelphia and an Archway study investigator. “With Susvimo, my patients now have an option that can help them maintain their vision as well as anti-VEGF injections, but on a more manageable twice-yearly treatment schedule.”

Susvimo delivers ranibizumab continuously, offering people living with wet AMD an alternative to anti-VEGF eye injections needed as often as once a month. The implant is surgically inserted into the eye during a one-time outpatient procedure and refilled every six months. If necessary, supplemental ranibizumab treatment can be given to the affected eye while the Susvimo implant is in place.

The approval is based on positive results from the Phase III Archway study primary analysis, described here in a previous post on this site.

Susvimo will be available in the United States in the coming months. For people who qualify, Genentech plans to offer patient assistance programs through Genentech Access Solutions. More information is also available at (866) 4ACCESS/(866) 422-2377 or http://www.Genentech-Access.com.

SOURCE: Genentech Press Release

Port Delivery System Under Priority Review by FDA

Frequent Eye Injections May Soon Be History

Genentech Pharmaceuticals has announced that the U.S. Food and Drug Administration (FDA) is giving priority review for the company’s Port Delivery System for the treatment of wet age-related macular degeneration (AMD). If approved, PDS will be a first-of-its-kind therapeutic approach, offering people living with wet AMD an alternative to frequent eye injections. The FDA is expected to make a decision on approval by Oct. 23, 2021.

As reported here earlier, PDS is a permanent refillable eye implant, approximately the size of a grain of rice, designed to continuously deliver a customized formulation of Lucentis over a period of up to six months with no reduction in safety or efficacy.

Genentech has a robust Phase III clinical development program underway for PDS, including the Portal, Pagoda and Pavilion studies. Portal is an extension study evaluating the long-term safety and efficacy of PDS in wet AMD. Pagoda is evaluating PDS for the treatment of diabetic macular edema (DME), while Pavilion is a study of PDS in diabetic retinopathy without DME. Both the Pagoda and Pavilion trials are actively recruiting participants.

SOURCE: Genentech Press Release

Rising Above COVID19 Depression

Prevalence of all forms of depression during the COVID19 pandemic was found to be 20% in a study population of 113,285 individuals.(1) Not unexpectedly, this is higher than the pre-pandemic rate. Compounded with already high levels of depression among those who are socially isolated due to visual impairment (2), this gives cause for increased concern about the mental health of older visually impaired people.  

Clinical depression is characterized by persistent, and nearly constant, states of these sadness and grief. Signs and symptoms include any of the following presenting for 2 or more weeks:(3)

Persistent sadness

Loss of interest in hobbies

Fatigue

Restlessness

Difficulty concentrating

Difficulty sleeping or getting out of bed

Changes in appetite

Thoughts of suicide

AMD is a common cause of visual impairment and blindness that affects nearly 196 million individuals worldwide, which is approximately 9% of the global population.(4) Depression and anxiety are more common in adults with visual impairment. Clinically significant subthreshold symptoms of depression are found in approximately one-third of older adults with AMD and impaired vision, which is nearly twice as high as the lifetime prevalence rates in the general older population.(4,5)

AMD is associated with increased functional disability and emotional stress, leading to an increased risk of mental health problems. Compared with other eye diseases, the rate of depression in older adults with AMD is the highest.(4) Other mental conditions, such as agoraphobia and social phobia, also are prevalent among those with visual impairment due to AMD.(4)

Although research has shown that behavioral interventions can treat or prevent depression in AMD(4), at this time, traditional low vision rehabilitation is considered the best treatment option, along with referral for mental health care when necessary. Because AMD can affect functional and psychological well-being, AMD patients should be aware that symptoms of depression can also be alleviated by treatments such as medication and psychotherapy(4) In addition, the National Suicide Prevention Lifeline is available 24 hours: 1-800-273-8255.

As social isolation requirements are beginning to ease, people affected by low vision and blindness should make an increased effort to re-enter circles of friends and family. Socialization is an important factor in  living well with low vision, so now is the time to renew and create acquaintences that are so necessary to healthy minds and bodies.

Author: Dan Roberts    

1. Audun Brunes, Trond Heir. Social interactions, experiences with adverse life events and depressive symptoms in individuals with visual impairment: a cross-sectional study (BMC Psychiatry. 2020 May 12;20(1):224. doi: 10.1186/s12888-020-02652-7. PMID: 32398122)

2. Ram Lakhan, Amit Agrawal, Manoj Sharma. Prevalence of Depression, Anxiety, and Stress during COVID-19 Pandemic(PMID: 33144785 PMCID: PMC7595780 DOI: 10.1055/s-0040-1716442)

3. Depression. National Institute of Mental Health. Updated February 2018. Accessed May 13, 2021. https://www.nimh.nih.gov/health/topics/depression/index.shtml

4. Zhang X, Olson DJ, Le P, Lin FC, Fleischman D, Davis RM. The association between glaucoma, anxiety, and depression in a large population. Am J Ophthalmol. 2017;183:37-41. doi:10.1016/j.ajo.2017.07.021

5. Brody BL, Gamst AC, Williams RA, et al. Depression, visual acuity, comorbidity, and disability associated with age-related macular degeneration. Ophthalmology. 2001;108(10):1893-1900; discussion 1900-1901. doi:10.1016/s0161-6420(01)00754-0

Age-Reversal Diet and Lifestyle Plan May Slow AMD Development

Several studies have identified specific nutrients and healthy behaviors as effective in delaying the development and slowing the progression of age-related diseases like macular degeneration. It has been said that the best cure for age-related macular degeneration (AMD) is to simply stop growing older. Now a pilot study of 43 men ages 50 to 72 may give that suggestion some veracity. Through a program of diet, sleep, exercise, and relaxation techniques, combined with supplemental probiotics and phytonutrients, a team of international scientists have described a plan that may actually reverse aging and its resultant effect on disease. 

In their study, the diet and lifestyle treatment group decreased in biological age by 3.23 years compared to the control group. The data also showed that those in the treatment group decreased in biological age by 1.96 years over the eight weeks. These results were determined by chemical analyses of the subjects’ DNA, and biological age was calculated using the Horvath DNA Methylation Clock. Scientists, by the way, have determined that predictions of mortality and multiple morbidities are better using biological age rather than chronological age.

The researchers gave well-supported rationales for each intervention in the plan, but they stress that slowing the aging clock may or may not actually curtail risks of age-related diseases. Still, the interventions used in the study are worth considering as an expansion upon the current recommendations for good eye health found on this website and many others. For that reason, they are outlined below as they were followed by the subjects in the 8-week program. It is important to remember that the researchers made choices based upon their knowledge of nutritives and activities providing optimum benefit to this study, but that is not to say that other options are not as beneficial. According to the authors:

“The combination of interventions used in this study may yet be improved upon and may be more impactful when further personalized. Future iterations of the intervention in continued clinical trials will attempt to optimize the program for efficacy, efficiency, scalability and affordability. An ever-evolving understanding of personalized application of such dietary and lifestyle interventions will likely lead to refinements to this kind of intervention that may further extend indicators of biological age.”

Dietary Prescription

Guidance per week:
3 servings of liver
  •(1 serving = 3 oz)
  •Preferably organic

5-10 eggs
•Ideally free-range, organic, omega-3 enriched

Guidance per day:
2 cups of dark leafy greens
  •Measured raw, chopped, and packed
  •Including kale, Swiss chard, collards, spinach, dandelion, mustard greens
  •Does not include salad greens such as romaine, iceberg, Spring mix

2 cups cruciferous vegetables
  •Measured raw, chopped, and packed
  •Includes broccoli, cabbage, cauliflower, Brussels sprouts, bok choy,   arugula, kale, mustard greens, watercress, rutabaga, kohlrabi, radish, Swiss chard, turnip

3 additional cups colorful vegetables of your choosing (excluding white potatoes, sweetcorn)

1-2 medium beet 4 tbsp (1/4 cup) pumpkin seeds (or pumpkin seed butter)

4 tbsp (1/4 cup) sunflower seeds (or sunflower seed butter)

1+ serving methylation adaptogens, choose from:
  •1/2 cup berries (wild preferred)
  •1/2 tsp rosemary
  •1/2 tsp turmeric
  •2 medium cloves garlic
  •2 cups green tea (brewed 10 minutes)
  •3 cups oolong tea (brewed 10 minutes)

6 oz animal protein
  •Grass-fed, pastured, organic and hormone/antibiotic-free

2 servings of low glycemic fruit

General guidance:
Organic preferred over conventional
Stay hydrated
Don’t eat between 7pm and 7am
Include “healthy” oils
  •Balance types of fat
  •E.g. coconut, olive, flaxseed and pumpkin seed oil
Avoid added sugar/candy, dairy, grains, legumes/beans Minimize plastic food containers
________________________________________________

Supplement Prescription
PhytoGanix® [or comparable product]*, a combination of organic vegetables, fruits, seeds, herbs, plant enzymes, prebiotics and probiotics.
UltraFlora® Intensive Care* [or comparable product], containing Lactobacillus plantarum 299v.

Exercise Prescription
Minimum of 30 minutes of exercise per day for at least 5 days per week, at an intensity of 60-80% of maximum perceived exertion.

Sleep Prescription
Average a minimum of 7 hours of sleep per night.

Stress Management Prescription 
Breathing exercise from Steps to Elicit the Relaxation Response developed by Herbert Benson MD, twice daily.

*PhytoGanix® and UltraFlora® Intensive Care are products of Metagenics, Inc., which supported this study with an unrestricted grant.
_______________________________

Author: Dan Roberts

SOURCE: Fitzgerald KN, et al. Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial. Aging (Albany NY). 2021; 13:9419-9432. https://doi.org/10.18632/aging.202913

New AMD Treatments Coming Soon

Sometimes it seems that retina research moves at a snail’s pace, but science is steadily moving toward those treatments and cures that will keep our eyes healthy. This is an update on four therapeutics just around the corner for treatment of age-related macular degeneration (AMD). Of the hundreds of ongoing clinical trials for both wet and dry AMD, these are the ones offering the most hope in the coming months.

RGX-314

Regenxbio’s RGX-314 uses a new method of inhibiting blood vessel growth (neovascularization) in wet age-related macular degeneration (wAMD). It differs from current therapeutics in that it includes a gene vector (NAV AAV8) which encodes an antibody fragment designed to neutralize VEGF (vascular endothelial growth factor) activity. As of December 31, 2020, delivery of RGX-314 was reported to be generally well-tolerated, with no evidence of inflammation. More information.

Faricimab

Roche has been studying faricimab for treatment of wet age-related macular degeneration (wAMD). The efficacy of faricimab administered at 12- and 16-week intervals was evaluated against ranibizumab (Lucentis) every 4 weeks. By January 2021, research had shown that people receiving faricimab injections at fixed intervals of up to every 16 weeks achieved visual acuity outcomes as effective as those receiving Regeneron’s aflibercept (Eylea) injections every eight weeks. Roche looks forward to submitting the data to global regulatory authorities, with the aim of bringing this new treatment option as soon as possible to patients. More information.

Port Delivery System

Developed by Genentech, the Port Delivery System (PDS) is a permanent eye implant about the size of a grain of rice that continuously releases a modified version of Lucentis. Once FDA approved, patients with wet age-related macular degeneration (wAMD) would visit their doctors only twice a year to refill the device–a significantly less burdensome and costly protocol. Rollout of the PDS is expected in the U.S. in 2021 and beyond the U.S. in 2022. More information.

APL-2

Apellis reported in August 2017 that injections of APL-2 demonstrated a significant slowing of the progression of dry age-related macular degeneration (atrophic AMD). Then, in October 2020, a phase 2 analysis found that the monthly treatment reduced the rate of progression to geographic atrophy (GA) by 39 percent in areas of the retina outside of existing GA lesions. Top-line results are expected in the third quarter of 2021. More information.


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Antiangiogenic Drugs for Wet AMD

A Guide to Research in Dry AMD

Neovascularization May Slow Progression of Geographic Atrophy

Neovascularization, or new blood vessel growth, is a restorative function of the body that assists in healing. When it occurs in the retina, however, it can lead to vision loss. In age-related macular degeneration (AMD) the photoreceptor cells weaken over time. In about 10 to 15 percent of AMD patients, the inflammatory system sends new blood vessels into the photoreceptor layer to carry nutrition to those cells. This process of inflammation is beneficial elsewhere in the body, but in the retina, if left untreated, it can cause permanent central vision loss.

Clearly, neovascularization in the retina has a negative effect that must be blocked. New research, however, suggests that it may actually be a double-edged sword. An AREDS2 Research Study Group has found in a follow-up study of 757 eyes with geographic atrophy (advanced dry AMD) that enlargement of the areas of cell degeneration seems to slow in some patients prior to leakage of the blood vessels (exudation). This means that the tissue could likely be benefitting from the improved blood circulation, while the vision of the patient is being simultaneously threatened by impending exudation.

The dichotomy presents some interesting therapeutic challenges that warrant further evaluation in prospective studies.

SOURCE: Progression of Geographic Atrophy with Subsequent Exudative Neovascular Disease in Age-Related Macular Degeneration AREDS2 Report 24. Christopher K. Hwang, MD, PhD, et al (Published October 15, 2020 DOI: https://doi.org/10.1016/j.oret.2020.10.008

New Website Brings AMD Groups Together

AMD Central.org provides access to resources for patients and caregivers in one location 

AMD Central logo

The American Macular Degeneration Foundation, BrightFocus Foundation, MD Support, Prevent Blindness and The SupportSight Foundation have launched AMD Central, an online resource that curates trusted information and tools from leading advocacy organizations to support the age-related macular degeneration (AMD) patient and caregiver community.

For many people with AMD, navigating the plethora of AMD websites can be overwhelming. Realizing there was an opportunity to improve this experience, AMD Central was created as a first-of-its kind resource for this community to help patients and caregivers more easily find AMD support in one place. It is designed to empower patients to take ownership of their eye condition as a catalyst to change the way they handle their health and wellness.

AMD Central features a wide range of resources, including clinical details about the condition and practical advice for living with low vision. The site was also developed with the accessibility needs of this community in mind: visitors are able to alter display settings on both desktop and mobile, many resources are available as both print and audio files to encourage utilization, and select materials are available in Spanish.

“When I was first diagnosed with AMD, I didn’t know where to start when it came to getting guidance,” said Sandy Seitz, a person living with macular degeneration. “AMD Central is absolutely the encyclopedia of macular degeneration! Whether you’re a patient or loved one looking for information, you can find the answers you need with just a few clicks.”

The creation of AMD Central was made possible through support from Novartis Pharmaceuticals Corporation.

To access AMD Central, visit www.AMDCentral.org.

Don’t Blame Everything On Your Macula

So your sight is slowly diminishing, and your ophthalmologist told you that nothing could be done. They said that the cells in the very center of your retina (the macula) are degenerating, and gradual loss of clear eyesight is to be expected. Still, they want to see you at least once a year unless you notice a sudden change in your vision.

Over the ensuing months, you dutifully check the Amsler grid taped to your mirror, one eye at a time as recommended, and you haven’t seen any reason to call the clinic. You do, however, notice that, sure enough, your vision is getting dimmer and less clear over time, just as you were told.

The year passes, and you have grown accustomed to making do with better lighting and magnification, even though you’re struggling more and more with seeing at a distance. You know about low vision rehabilitation opportunities, but your vision is not severe enough for qualification, and you feel that you don’t yet need that kind of intervention. You ask yourself, “Do I really need to make that appointment? I’m seeing a little more blurriness and glare, but nothing the doctor can fix. So maybe I’ll save the time and trouble of getting to the clinic and sitting for hours in that waiting room”.

Here’s something to consider before making that decision:

Your progressive vision loss could be blamed on more than your macula. Your diminishing eyesight might signify one or more conditions that can be treated, even if your macula cannot. If you have another condition affecting your vision, that’s called a co-morbidity. You may not know that your doctor examines you for co-morbidities, an especially important protocol for aging eyes. If any are found, they may or may not tell you right away, but they will make a note in your record for follow-up and possible treatment.

The National Eye Institute (NEI) defines common causes of vision loss that can occur simultaneously with retinal disease in senior adults. The number of possibilities might surprise you, but the good news is that many of them are treatable if identified in time. In addition to tracking the progression of your macular condition, a regular dilated exam for co-morbidities is an important reason for that annual visit with your doctor. You might find that you have an alternative explanation for your worsening vision that can be corrected. As described by the NEI, here are the five most common treatable vision problems in older adults that cannot be blamed on the macula:

Cataract
A cataract is a cloudy area in the lens of your eye. Cataracts are very common as you get older. In fact, more than half of all Americans age 80 or older either have cataracts or have had surgery to get rid of cataracts. More information: https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/cataracts 

Dry Eye
Dry eye happens when your eyes don’t make enough tears to stay wet, or when your tears don’t work correctly. This can make your eyes feel uncomfortable, and in some cases it can also cause vision problems. More information: https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/dry-eye

Floaters
Floaters are small dark shapes that float across your vision. They can look like spots, threads, squiggly lines, or even little cobwebs. More information: https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/floaters 

Glaucoma
Glaucoma is a group of eye diseases that can cause vision loss and blindness by damaging . . . the optic nerve. More information: https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/glaucoma 

Refractive Errors (presbyopia, astigmatism, nearsightedness, farsightedness)
Refractive errors happen when the shape of your eye keeps light from focusing correctly on your retina. Sometimes, all you need is better eyeglasses. More information: https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/refractive-errors

Take-away: Your annual exam may take a day out of your year, but it could add years to your vision!

by Dan Roberts, Editor-in-Chief
Living Well With Low Vision

Latest statistics on prevalence of blindness and low vision worldwide

The Vision Loss Expert Group (VLEG) has published new findings about four areas of interest to the blind and low vision community. The report provides timely updates on acuity measurement standards, prevalence of global cases, and prevalence of types of blindness and vision impairment.

For those who are interested in statistics, here are summaries of the report published in the February 2021 edition of The Lancet Global Health:

Definitions of acuity levels of visual impairment

Normal: 6/6 (US: 20/20)
Mild: 6/12 to 6/18 (US: 20/30 to 20/60)
Moderate to severe: 6/18 to 3/60 (US: 20/60 to 20/400)
Blind: Greater than 3/60 (US: 20/400) or less than 10° central field

Estimated mean numbers affected by blindness and vision impairment

Mild: 258 million
Moderate to severe: 295 million
Blind: 43.3 million

Causes of moderate-to-severe vision impairment in people age 50+

Age-related macular degeneration: 196 million (1)
Diabetic retinopathy: 93 million
Inadequate vision correction: 86.1 million
Glaucoma: 79.6 million (2)
Cataract: 78.8 million (3)

Causes of blindness in people age 50+

Cataract: 20 million
Glaucoma: 3.6 million
Inadequate vision correction: 2.3 million
Age-related macular degeneration: 1.8 million
Diabetic retinopathy: 0.86 million

In view of these numbers, the VLEG notes that, over the past three decades, the prevalence of blindness caused by cataract, glaucoma, and age-related macular degeneration has decreased in older adults. At the same time, however, the prevalence of blindness has increased. This suggests that improvements in treatment, pharmacology, and surgical interventions for some eye diseases are yielding success, but that more effort is needed to meet the increasing needs of an aging and growing population.
__________________________________

References to statistics not included in the VLEG report:

1. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Wong WL, et al. Lancet Glob Health. 2014 Feb;2(2):e106-16. doi: 10.1016/S2214-109X(13)70145-1. Epub 2014 Jan 3. PMID: 25104651

2. Glaucoma Information

3. Global prevalence and major risk factors of diabetic retinopathy. Joanne W Y Yau, et al. PMID: 22301125 PMCID: PMC3322721 DOI: 10.2337/dc11-1909

Newest Sustained-Release Anti-VEGF Drug in Trials

EyePoint Pharmaceuticals, Inc. announced on January 28, 2021 that the first patient has been dosed in their Phase 1 clinical trial of EYP-1901.  

EYP-1901 is a potential twice-yearly sustained delivery intravitreal anti-VEGF treatment for wet age-related macular degeneration (wAMD). It is the newest of several sustained delivery drugs under study, this one promising to extend to six months the time between injections. It is initially being developed as a treatment for wAMD, but researchers are looking forward to the added potential for treatment of diabetic retinopathy and retinal vein occlusion.

The company is looking forward to seeing initial data from the Phase 1 trial as early as the second half of 2021. 

See summary of all leading anti-VEGF drugs in clinics and currently under study.

Source: EyePoint Pharmaceuticals, Inc.

Faricimab for wet AMD effective at 16-week intervals

Genentech has announced positive topline results from its Phase III studies, TENAYA and LUCERNE, evaluating its new drug faricimab, for people with wet (neovascular) age-related macular degeneration (nAMD). Both studies have shown that people receiving faricimab injections at fixed intervals of up to every 16 weeks achieved visual acuity outcomes as effective as those receiving Regeneron’s aflibercept (Eylea) injections every eight weeks.

Thus far, Regeneron’s aflibercept (Eylea) and Genentech’s ranabizumab (Lucentis) and off-label bevacizumab (Avastin), have been the only drugs shown to be safe and effective for only as long as eight weeks between injections. Another drug, brolucizumab (Beovu), has been shown to be effective for up to twelve weeks, but it is currently being investigated by the drug’s manufacturer, Novartis, for potential adverse events in some patients.

Information about all leading anti-VEGF treatments in clinics and under study.

This is the first time this level of durability has been achieved in a Phase III study of an injectable eye medicine for nAMD. In both studies, faricimab was generally well-tolerated, with no new or unexpected safety signals identified. The faricimab studies are expected to be completed in September 2021.

More information about the faricimab studies

Looking Forward to 2021

Even the most optimistic person will admit that 2020 was a 365-day slog through dangers, disasters, and disappointments. In a year that offered little relief, considering that its famous number might have been expected to boost our spirits with good news about vision. And that’s why it might help us to look ahead at some promising events during the coming new year.

First treatment for geographic atrophy

Earlier this year, Apellis announced the completion of patient enrollment in the ongoing Phase 3 DERBY and OAKS studies investigating APL-2 in patients with geographic atrophy (GA), the advanced form of dry age-related macular degeneration affecting approximately five million people globally.

No approved treatment has yet been approved for GA, but the year 2021 may see that happen. APL-2 is the only targeted complement system therapy in Phase 3 clinical trials for GA. Trial results have found that monthly injections of APL-2 reduced the rate of progression to GA by 39 percent in areas of the retina outside of areas with prior damage. Top-line results from these pivotal trials are expected in the third quarter of 2021.


New delivery method for anti-VEGF drug in treatment of wet AMD

Genentech has now announced that Phase III trial data on their port delivery system (PDS) enabled over 98% of patients to go six months between clinical visits for treatment of wet AMD. The PDS is a tiny refillable implant that provides patients continuous delivery of Lucentis as necessary.

The PDS is the first wet AMD therapy to achieve positive Phase III results for this extended length of time between treatments. The current standard of care for wet AMD requires eye injections of anti-VEGF therapy as often as monthly to help maintain vision gains or prevent vision loss. This high treatment burden can lead to under-treatment and, potentially, less than optimal vision outcomes.

With approval of the PDS in 2021, clinical use will not be far behind, and patients can say goodbye to needles.


Collaboration among major AMD organizations to be unveiled

For the first time, all major age-related macular degeneration organizations are collaborating to help patients and caregivers more easily find resources about AMD. Navigating the plethora of AMD information online can be overwhelming, and many people don’t know where to start. But now a new website, to be unveiled before the summer of 2021, will help resolve that issue.

The site is being designed to empower patients and their caregivers to take ownership of their eye condition as a catalyst to change the way they manage their health and wellness. It will help patients and family members learn about AMD clinically and provide practical advice for living with low vision so that they can better manage the disease.

The contributing nonprofit patient advocacy organizations are all trusted members of the vision community and are crucial in supporting people impacted by AMD. Look for announcements in the Spring.


TeleHealth is making doctor visits easier

Telehealth is a service made available by way of telecommunication devices like computers and smart phones. Using this recent technology, people who find it difficult to visit their physicians regularly can be diagnosed and monitored remotely and can take part in live consultations from home.

According to a survey conducted by Updox, a significant percentage of users find telehealth visits to be more convenient than in-person appointments, they are grateful for not having to be exposed to other people, they like that scheduling appointments is easier, and they find follow-ups to be more streamlined.

Telehealth appears to be here to stay. If the technology remains user-friendly, and if it gains wide professional acceptance, remote clinical visits could greatly ease the burdens of time and cost on doctors and patients alike.

More information


Artificial intelligence is making us more efficient

Artificial intelligence (AI) makes it possible for machines to learn from experience, adjust to new inputs, and perform human-like tasks. It provides us with human-like interactions with computers and helps us with difficult decision making.

AI processing allows computers to perform human-like tasks, such as recognizing speech, identifying images, or making predictions. It helps computers understand, interpret, and manipulate human language. It is what helps computers communicate with humans by reading text, hearing and interpreting speech, recognizing emotion, and determining which of those parts are important.

AI is in the process of incorporation into many devices for blind and visually impaired people. Such devices include self-driving vehicles, reading machines, face recognition software, and navigation software.

2021 will see AI playing a major role by ensuring drug safety, hastening development of new therapies, ensuring more accurate diagnostic and treatment choices, and improving the quality of our daily lives. The capabilities of AI in tandem with eye care, diagnosis, and treatment are being dramatically realized, with new uses seemingly being discovered daily.


These are five positive reasons for optimism about 2021. That’s five times the number we can attribute to 2020. And that doesn’t even include the most exciting event yet to come: the end of the worst pandemic the world has ever seen.

Thanks to the amazing science that will bring the virus under control, and to the personal sacrifices we have made, we will recreate our sense of normalcy. And, as we have learned throughout history, that new normalcy will be based upon important things we have learned about ourselves and our planet. Let’s look forward to that new day!

Dan Roberts
Editor-in-Chief
Living Well With Low Vision

Dry Eye and Dry Macular Degeneration Are Different Conditions

Some people are confusing the eye conditions called “dry eye disease” and “dry age-related macular degeneration” (dry AMD). The confusion is understandable, but the two conditions are nothing alike. 

Dry eye disease occurs when tears are not sufficient enough to provide necessary lubrication for the eyes. This problem can lead to inflammation and damage of the cornea covering the front of the eyeball. Treatments include behavioral or environmental changes and/or eyedrops to relieve stinging and burning. Dry eye disease properly treated will not progress to permanent vision loss.

Conversely, dry AMD effects the retina, which lines the inside back of the eyeball. The result of aging and thinning of the retinal tissue, dry AMD can lead to gradual impairment of central vision in senior adults. The term “dry” differentiates it from “wet” AMD, wherein blood vessels grow and leak into the retina. No medical treatment or cure for dry AMD is yet available, but good research is progressing in the areas of pharmacology, genetics, and stem cell therapeutics. 

Clarification of the terminology is important at the time of diagnosis, since treatment and care for each disease is vastly different, not to mention the emotional upset that can be caused by misunderstanding.

For more information about dry eye disease, see:

https://www.mayoclinic.org/diseases-conditions/dry-eyes/symptoms-causes/syc-20371863

For more information about dry AMD research, see:

https://webfrenetics.com/2013/05/30/a-guide-to-research-in-dry-amd/

Beware UVC Lamps as COVID-19 Disinfectant

Since the outbreak of COVID-19 disease, consumers’ interest in ultraviolet-C (UVC) lamps has increased for use in disinfecting surfaces in the home or similar spaces. The U.S. Food and Drug Administration (FDA) has received reports of skin and eye burns resulting from improper use or installation of UVC lamps.

Such lamps fall into four categories:

  • Low-pressure mercury
  • Excimer lamp or Far-UVC
  • Pulsed xenon
  • Light-emitting diodes (LEDs)

The effectiveness of UVC lamps as a disinfectant for COVID-19 depends upon the wavelength, dose, and duration of radiation exposure. Precise data is still being collected, but it is inarguable that direct exposure of skin and eyes to UVC radiation from some UVC lamps may cause painful eye injury and burn-like skin reactions.

The FDA recommends never looking directly at a UVC lamp source, even briefly. Doing so can lead to redness, blurred vision, tearing, light sensitivity, or general pain of the eyes. If anyone experiences these symptoms associated with using a UVC device, they are encouraged to see their eye care specialist for treatment, and report it to the FDA.

For more details on the risks and efficacy of UVC as a COVID-19 disinfectant, see UV Lights and Lamps: Ultraviolet-C Radiation, Disinfection, and Coronavirus.

How well are you adapting to visual impairment?

How can you tell if you are adapting as well as possible to the most important facets of your everyday life? 

A new self-survey is helping visually impaired and blind individuals score how well they are adapting. It is similar to a needs assessment questionnaire used by rehabilitation specialists, but it is designed for self- analysis at home. Individuals with corrected bilateral visual acuity of 20/70 or worse will benefit the most.

53 questions were drawn from the most significant everyday living issues faced by visually impaired individuals. Simple yes-or-no answers result in a score analysis that helps respondents understand what they can do to maximize their adaptability to vision loss. Toward that end, most questions are followed by links to helpful resources. The survey may be taken online or it may be printed out, and the responses are totally private.

According to Dan Roberts, Director of MD Support and developer of the survey, “We have little choice when it comes to vision loss, but we do have good opportunities to help us adapt to it. I hope this will offer visually impaired individuals comfort in the knowledge that all possibilities for successful self-maintenance are being addressed, or that it will encourage them to initiate ways to make their lives easier.”

Go to the Adaptability Survey

Download the printable PDF format (13 pages)

Lucentis Substitute In Phase 3 Trials

Samsung Bioepis is reporting first year results from their phase 3 study of a proposed lucentis biosimilar (SB11). 

A biosimilar is a biological product (derived from a living organism)  that shows no clinically meaningful differences from another biologic (eg. Lucentis). This study has shown that, at 52 weeks, primary end points were met for visual acuity and retinal health, suggesting that it could become a substitute for Genentech’s Lucentis (ranabizumab). This would be the first biosimilar for an anti-VEGF drug, which could lead to significant cost savings for the U.S. health system and consumers.

Results of the study will be presented at the American Academy of Ophthalmology 2020 Virtual meeting from November 13 to 15, 2020.

SOURCE: Samsung Bioepis’ Ranibizumab Candidate Shows Equivalence in Updated Results 

Vitamin D3 and Omega-3 Offer No Protection Against AMD

Observational studies have suggested that higher intake or blood levels of vitamin D and marine omega-3 fatty acids may be associated with lower risks of age-related macular degeneration (AMD). A recent large randomized trial (VITAL), however, has concluded that supplementation with vitamin D3 and marine omega-3 fatty acids actually had no significant overall effect on AMD incidence or progression.

25,871 adult US men and women, mean age 67.1, consumed daily supplementation with vitamin D3(2000 IU) and marine omega-3 fatty acids (1 g) for a median of 5.3 years. Randomization was from November 2011 to March 2014, and study pill-taking ended as planned on December 31, 2017. This the first randomized trial to examine vitamin D in AMD prevention. On the other hand, omega-3 has been studied in two past trials, most notably the AREDS2, but results have been uncertain.

In view of several minor limitations, the VITAL study has offered the most solid evidence to date that neither vitamin D3 nor omega-3 supplementation, while beneficial for other conditions, offer no specific prevention against AMD.

SOURCE:

Effect of Vitamin D and ω-3 Fatty Acid Supplementation on Risk of Age-Related Macular Degeneration: An Ancillary Study of the VITAL Randomized Clinical Trial. William G. Christen, ScD1 (JAMA Ophthalmol. Published online October 29, 2020. doi:10.1001/jamaophthalmol.2020.4409)

Smoking and Wet AMD Treatment

It has long been known that cigarette smoking reduces levels of plasma antioxidant, which protects retinal cells. It is also suspected as a contributor to cataract formation, restriction of night vision, and amblyopia (“lazy eye”). As reported in the September 2020 issue of the journal, Retina, a research team has confirmed the effect of smoking on the one-year visual outcomes in eyes treated with anti-VEGFs for wet (neovascular) age-related macular degeneration (nAMD). 

After analyzing 837 patients with nAMD from 2006 to 2016, researchers found that current smokers have an up to sevenfold greater risk of developing nAMD than nonsmokers, and they tended to have a more aggressive disease state. Additionally, nonsmokers who underwent anti-VEGF treatment were found to have more than twice the gain in visual acuity after a year.

This finding adds to the literature on the ill effects of smoking on people with either dry or wet AMD. The reason for the association between current smoking and poorer visual outcomes with anti-VEGFs is still not totally understood, but research has found that a genetic component (specifically the LOC387715 gene) is likely involved.

SOURCES:

“Smoking Status and Treatment Outcomes of Vascular…” . Vittorio AF, Nguyen V, Barthelmes D, et al. Retina 2020;40:1696-1703. 

“No Smoking” by Linda Kaspari (published online at Living Well With Low Vision, 2006)

Anti-VEGF treatment maintains acuity over 10 years

Patients receiving continuous injections of anti-VEGF drugs for treatment of wet age related macular degeneration (wAMD) can take comfort in knowing that they are keeping their initial visual acuity long term. As reported in the September 29 issue of  Ophthalmology Retina, the LATAR study found that 293 eyes not only maintained their original visual acuity, but showed a mean gain of 3 letters over the decade. 

A common question among wAMD patients is, “Aren’t these drugs going to be harmful after so many injections?” The results of this study have addressed that concern, with a total of about 58 injections per person from 2006 through 2016. This information can reduce worries about loss of acuity, but care must still be taken to avoid risks such as infection, contamination, and increased eye pressure. In the hands of a conscientious specialist, patients can look forward to maintaining their vision for many years or until improved methods of drug delivery are developed.   

SOURCE: Long-term anti-VEGF treatment for neovascular age-related macular degeneration. The LATAR Study Report 1: Ten-year, real-world outcomes. Kimberly Spooner, et al (Ophthalmol Retina. 2020 Sep 29;S2468-6530(20)30399-7. doi: 10.1016/j.oret.2020.09.019. Online ahead of print.

Levodopa may improve vision in patients with Wet AMD

Investigators have determined that treating patients with the early wet form of age-related macular degeneration (AMD) with levodopa, stabilized and improved their vision. Levodopa is a safe and readily available drug commonly used to treat Parkinson’s disease,

The drug reduced the number of treatments necessary to maintain vision, and as such, will potentially reduce the burden of treating the disease, financially and otherwise. Their findings appear in the American Journal of Medicine, published by Elsevier.

The investigators developed two proof-of-concept studies to test whether levodopa improves visual acuity and the anatomical changes caused by nAMD. This trial demonstrated for the first time that levodopa is safe, well-tolerated, and delayed anti-VEGF injection therapy while improving visual outcomes. In the first month, retinal fluid decreased by 29 percent. After six months the decrease in retinal fluid was sustained and mean visual acuity improved enabling patients to read an additional line on the eye chart. This is the equivalent of improvement from 20/40 to 20/32. Side effects were limited. 

The investigators noted that levodopa may be unlikely as a standalone treatment in patients with newly diagnosed nAMD since 11 of the patients did require anti-VEGF injections. However, they required fewer than the standard monthly treatments, and in the second group, monthly injections of anti-VEGF decreased by 52 percent.

In spite of the small sample size and limited patient diversity, the findings suggest efficacy and support the targeting of the GPR13 receptor (which is supportive of retinal health and survival) with levodopa for the treatment of nAMD in future studies.

SOURCE: News Release

Innovative Glaucoma Platform Launched

It has been said, “Just because you have the measles doesn’t mean you can’t catch chicken pox”. Many people affected by macular degeneration and other diseases of the eye have learned that glaucoma is often a secondary condition with which they must also deal.

“Today, there are more than an estimated 3.2 million Americans that have glaucoma,” said Jeff Todd, President and CEO of Prevent Blindness. “By creating new resources, our goal is to provide the information and support that patients and their caregivers need to help prevent significant vision loss from the ‘Sneak Thief of Sight,’ as glaucoma is commonly called.”

Toward that goal, Prevent Blindness and Responsum Health have launched an online knowledge platform for patients with glaucoma. Called “The Glaucoma Community”, the platform can be accessed for free via web browser or mobile app.

The Glaucoma Community provides users with a toolkit of useful, community-oriented features:

  • A personalized Newsfeed delivers easy-to-read daily summaries of important glaucoma news and information from across the Internet, all of which is written by professional health writers and vetted by Prevent Blindness reviewers.
  • Community Chat is a moderated social wall where users can share experiences and advice in up to seven languages.
  • Patient One-Sheet allows patients to easily collect, maintain, and print their key medical information in a secure format.
  • Access to a robust collection of trusted patient resources, including financial assistance programs and glaucoma support groups.

The Glaucoma Community was made possible by a grant from The Allergan Foundation.

“While the Internet offers the promise of unlimited access to information,” said Andrew M. Rosenberg, Founder and CEO of Responsum Health, “individuals with glaucoma can easily find themselves overwhelmed by too much content or underserved by inaccurate, inappropriate, or overly complex content. The Glaucoma Community solves that problem. We are excited to be partnering with Prevent Blindness to bring people with glaucoma a state-of-the-art app to help them better understand their treatment options, develop strategies to improve their health and quality of life, and find community among others who are facing the same challenges from this chronic disease.”

More information.

Download the app

SOURCE: Press Release

Zimura® Shows Significant Suppression of Geographic Atrophy

IVERIC bio, Inc. has announced positive Phase 3 results from its GATHER1 clinical trial with Zimura® (avacincaptad pegol). As published in the September issue of Ophthalmology®, Zimura® met its pre-specified primary efficacy endpoint at 12 months and reached statistical significance in GATHER1, an international, multicenter, randomized, double masked, sham controlled clinical trial. 

Zimura® inhibits complement factor C5, which is believed to be involved in the development of AMD. The reduction in the mean rate of geographic atrophy (GA)  growth over 12 months was better than 27% group as compared to sham control groups. The data was statistically significant, and the drug was generally well tolerated.

“GATHER1 is currently the only Phase 3 clinical trial I am aware of showing early suppression of GA growth which continued throughout the trial with continuous treatment out to 18 months,” said Glenn Jaffe, M.D., (lead author) and Robert Machemer (Professor of Ophthalmology, Duke University). 

GATHER2 is currently underway to further evaluate the efficacy and safety of Zimura in patients with GA.

For summaries of all leading studies for dry AMD, see A Guide to Research in Dry AMD.

SOURCE: Press Release

AAO Cautions About Red Light Therapy

An article published here in August 2020 announced that positive results were obtained from a study of photobiomodulation (PBM)–also known as “red light therapy”– as a treatment for eye diseases such as AMD, retinopathy of prematurity, and diabetic macular edema. The American Academy of Ophthalmology has simultaneously posted cautionary remarks about recent PBM research.

In the AAO news release published online August 15, 2020, Ninel Z. Gregori, MD (Bascom Palmer Eye Institute, Miami) is quoted as saying, “Based on research so far, there is some evidence that light therapy has the potential to improve eye health . . . But we need a lot more data in humans before it can be used to treat ocular disease or aging eyes.”

More testing in human clinical trials is therefore needed to positively determine safety and most effective methodology of treatment. It is the opinion of Living Well With Low Vision that PBM is obviously not a procedure that should be attempted at home, where no safety protocols are in place.

Light Therapy Showing Success As Retinal Treatment

According to an article in the August 6, 2020 edition of Ophthalmology Times, a procedure called photobiomodulation (PBM) has had recent success in treating eye diseases such as AMD, retinopathy of prematurity, and diabetic macular edema.

PBM, or low-level light therapy, is the application of monochromatic light to a part of the body with the aim of repairing tissues and reducing inflammation, edema, and pain. Like photosynthesis in plants, light in the far red and near-infrared spectral range, can stimulate the cells, causing a cascade of photochemical reactions that can reduce oxidative stress. Oxidation is well-known to be a primary cause of retinal degeneration.

PBM has been found to be safe, has no side effects, and is completely noninvasive. Nine PBM cycles were administered to a patient over 1 month. After 1 month and 6 months, the OCT scan showed reduced drusen. The patient obtained subjectively improved vision, less eye strain, more color contrast, higher definition, and better far and near uncorrected visual acuity. Contrast sensitivity improved from 1.8 to 2.0. Outcomes remained stable at the 6-month follow-up.

According to author Robert Pinelli, MD, “This case demonstrates a successful noninvasive treatment with improved quality of vision in dry AMD. Irradiation could, therefore, offer a new, noninvasive, adverse effect–free means of stimulating retinal stem cells to regenerate.”

SOURCE: “Photobiomodulation shows the power of light” by Robert Pinelli, MD (Ophthalmology Times, August 6, 2020). Published online at https://www.ophthalmologytimes.com/view/photobiomodulation-shows-the-power-of-light

“Lookout” app now available for all Android devices

We reported here in March 2019 that Google had created a new Android app called Lookout to help the visually impaired. Similar to Microsoft’s Seeing AI for Apple devices, the application uses artificial intelligence (AI) combined with Talk Back to identify objects, read text, scan barcodes, and identify currencies.

At that time, Lookout was available only for Google’s Pixel devices in the U.S. Now, however, the company has updated the app for all Android devices and includes “Scan Document”, which takes a snapshot of a letter or other documents and reads it aloud, and “Food Label”, which identifies packaged food labels. 

The app is available at no cost from the Google Play Store for any Android device with more than 2GB of RAM and running Android 6.0 or newer.

Gene therapy treatment for wet AMD shows positive results

(Updated 12/11/2020)

REGENXBIO, Inc. has reported positive one year data from patients in Cohorts 4 and 5 of the Phase I/IIa trial of RGX-314 for the treatment of wet age-related macular degeneration (wet AMD). As reported here in June 2017, RGX-314 is being developed as a one-time sub-retinal injection for wet AMD. It would be a significant improvement over current anti-VEGF therapies requiring repetitive and frequent intraocular injections. 

RGX-314 differs from current therapeutics in that it includes a gene vector (NAV AAV8) which encodes an antibody fragment designed to neutralize VEGF (vascular endothelial growth factor) activity. This modifies the pathway for formation of new leaky blood vessels which lead to retinal fluid accumulation and vision loss.

“Based on the overall results to date from the Phase I/IIa trial, I believe that RGX-314 has the potential to profoundly impact all aspects of clinical management for patients with wet AMD,” said Robert Avery, M.D., Founder of California Retina Consultants and Research Foundation and investigator surgeon in the trial. “Wet AMD affects a large number of adults, and often results in loss of vision over time due to non-compliance with the current standard of care of frequent anti-VEGF injections. I am encouraged that RGX-314 has the potential to become a one-time gene therapy treatment option for a broad range of patients.”

REGENXBIO has announced dosing of the first patient in the Phase II ALTITUDETM trial of RGX-314 for the treatment of diabetic retinopathy using suprachoroidal delivery. REGENXBIO expects to report initial data in 2021

For further details on the trial, enrollment criteria and eligibility, visit https://clinicaltrials.gov/ct2/show/NCT03066258.

SOURCE:  Press release


AMD associated with greater COVID mortality

The human’s natural immune system (called complement) has been found to be associated with the severity of COVID disease in people with age-related macular degeneration (AMD), according to a new study published in Nature Medicine. A hyperactive complement system is known to be directly related to development of AMD.

In a retrospective observational study of patients with SARS-CoV-2 infection, researchers at Columbia University Irving Medical Center found that people with AMD are at greater risk of developing more serious complications and dying from COVID than people who have normally-functioning complement systems. In the study, out of 88 people identified with AMD, over 25% died from the virus, compared to the average mortality rate of 8.5 per cent. Additionally, about 20% required intubation.

One explanation is provided by researchers Sagi Shapira, PhD, MPH, and Nicholas Tatonetti, PhD (professors at Columbia University Vagelos College of Physicians and Surgeons). Corona viruses have been found to be proficient at mimicking proteins, particularly those involved in coagulation and those that make up the complement system. Such proteins are normally beneficial, as they help eliminate pathogens like bacteria and viruses. Hyperactivity of the proteins, however, can also increase coagulation and inflammation in the body, causing more harm than good. The new coronavirus, COVID-19, may be doing just that.

It is important to remember that these are early results from a small retrospective study, which shows only an association between AMD and severity of COVID disease. Further analysis with larger clinical cohorts is warranted before a causal relationship can be established. Meanwhile, people with AMD might be well-advised to take extra precautions against exposure to the COVID-19 virus.

SOURCE: Ramlall, V., Thangaraj, P.M., Meydan, C. et al. Immune complement and coagulation dysfunction in adverse outcomes of SARS-CoV-2 infection. Nat Med (2020). https://doi.org/10.1038/s41591-020-1021-2

New Drug For Wet AMD Should Be Used With Caution

Beovu (brolucizumab) for wet AMD is the newest anti-VEGF drug on the market. It has been shown to be an effective and long-lasting inhibitor of blood vessel development (neovascularization) in the retina. The drug’s manufacturer has, however, been recently investigating incidences of severe intraocular inflammation (vasculitis) and retinal artery occlusion that were reported after their product was approved in October 2019.

Beginning in March 2020, a retro­spective analysis of retinal vasculitis in 12 female patients from 10 U.S. centers was conducted. They found that the patients’ visual acuity had decreased significantly over a period of around 25 days following injection. Until a cause for the problem is determined, retinal specialists are being advised to avoid using Beovu. Those who wish to continue are encouraged to check for any sign of active inflammation in the patient’s eye before proceeding.

Novartis, makers of Beovu, initiated its own internal review of these post-marketing safety case reports, including the establishment of an external safety review committee (SRC) to provide an independent, objective review of these cases and a comparison with events seen in the Phase III trials (HAWK & HARRIER). Novartis has also convened a fully dedicated team collaborating with top global external experts, leveraging the collective multidisciplinary expertise to examine the root causes, potential risk factors and mitigation of these adverse events. The latest updates can be found at brolucizumab.info.

Are some patients with CNV unresponsive to anti-VEGF?

Since 2004, anti-VEGF drug injections have been shown to be highly effective in suppressing choroidal neovascularization (CNV) in the retinas of people with wet age-related macular degeneration and diabetic retinopathy. They have also been shown to suppress further CNV for as long as 12 weeks, depending upon the drug being used and the disease state of the patient. 

Some patients, however, are not responding to the therapy as expected. In spite of receiving the recommended protocol of injections every 4 weeks for at least the first 3-4 months, they are experiencing continued CNV as soon as 3 weeks after treatment. Doctors have been considering such patients “nonresponsive” and resorting to alternate or combination therapies.

But now, researchers from Harvard Medical School have come up with a contradiction to the notion that patients can be nonresponsive. They have looked at the original data from Genentech’s Lucentis (ranibizumab) study and determined that these so-called nonresponders may simply require more frequent dosing. They found this in details of Genentech’s PrONTO study, in which data on subjects with persistent CNV at 2 weeks were averaged into the data on subjects at 4 weeks.

To pursue their theory, Demetrios G. Vavvas, MD, PhD and Saghar Bagheri, MD, PhD conducted a multicenter 48 patient study. They found that optimal dosing might be shorter than 4 weeks for a sizable percentage of patients, and most patients who were considered poor or nonresponders may be seen as responding if they are evaluated prior to the standard 4-week assessment.

They concluded that these results imply that, with a current dosing regimen of 4 weeks or more, suppression of VEGF for many patients may actually exacerbate progression of CNV. Further study will be necessary to confirm this before accelerated dosing will be advised.

For a more detailed description of the study, see https://www.ophthalmologytimes.com/therapeutics/helping-patients-who-do-not-respond-anti-vegf-therapy

Telehealth usage increases during COVID-19

A survey of 2,000 adults in the U.S. has shown that 42% have used telehealth services in place of their regular in-person visits to eye clinics since the beginning of the COVID-19 pandemic in March 2020. Telehealth is a service made available by way of telecommunication devices like computers and smart phones. Using this recent technology, people who find it difficult to visit their physicians regularly can be diagnosed and monitored remotely and can take part in live consultations from home. 

According to the survey, conducted by Updox, a virtual care and health communication company, 65% of users find telehealth visits to be more convenient than in-person appointments, and 63% say they are grateful for not having to be exposed to other people. 44% and 38% respectively of the users in the survey also liked that scheduling appointments was easier, and follow-ups were more streamlined.

It appears that telehealth will be here to stay, even after the COVID-19 pandemic is under control. 51% of respondents said that they are likely to continue post-pandemic, due to its convenience and the ability to interact with the physician of choice. If the technology remains user-friendly, and if it gains wide professional acceptance, remote clinical visits could greatly ease the burdens of time and cost on doctors and patients alike.

OpRegen® for geographic atrophy maintains positive results

Lineage Cell Therapeutics (originally BioTime, Inc.) has announced positive results with its experimental OpRegen® therapy for geographic atrophy (GA), the advanced stage of dry macular degeneration.

The company began enrolling and treating U.S.-based patients in 2017 under David S. Boyer, M.D. (Retina-Vitreous Associates Medical Group, Los Angeles) and H. Richard McDonald, M.D., (West Coast Retina Medical Group, San Francisco).

OpRegen® is an investigational therapy in which retinal pigment epithelial (RPE) cells are introduced into the subretinal space, where they are intended to replace missing RPE cells. Phase 1 results showed that OpRegen® caused no serious adverse events, and retinal imaging suggested the presence and survival of transplanted cells in the subretinal space for up to one year.

In May 2020, researchers reported to the 2020 Association For Research In Vision and Ophthalmology (ARVO) that positive results are continuing to come from the Phase 1/2 study, including gains in visual acuity, reduced geographic atrophy (GA) progression, and improved reading speed. In one patient of 17 so far enrolled, geographic atrophy was 25% smaller at 9 months than at baseline. In the next 6 months, the area grew approximately 50% slower than its historical rate.

Brian Culley, CEO of Lineage Cell Therapeutics, said, “Our data are early, and we need to continue testing, but we are encouraged by early evidence that transplanting our retina cells may lead to an increase in letters read by some patients.”

SOURCE: Lineage Cell Therapeutics

Experimental stem cell treatment continues to maintain vision

A procedure reported here in March 2018 has been shown to continue being a safe and effective method for introducing stem cells into the retina. Eye researcher Professor Pete Coffey, who founded the London Project over a decade ago, has confirmed that two study patients have maintained improvements in their vision five years after surgery. They have gone from not being able to read at all to reading 60 to 80 words per minute with normal reading glasses.

Implantation of a specially engineered patch of retinal pigment epithelium (RPE) cells derived from stem cells has restored vision in the subjects, both of whom are affected by 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 study investigated whether the diseased cells at the back of the patients’ affected eye could be replenished using the stem cell patch. A specially engineered surgical tool was used to insert the patch under the retina in the affected eye of each patient in operations lasting one to two hours.

This is a major milestone for the London Project. The stem cell-derived ocular cells were developed in part by researchers at UC Santa Barbara.

“This study represents real progress in regenerative medicine and opens the door on new treatment options for people with [AMD],” said Coffey,  “We hope this will soon lead to an affordable ‘off-the-shelf’ therapy.”

It is important to remember that only the retinal pigment epithelial (RPE) cells are being treated in this study. The RPE is the layer of cells that nourish the photoreceptor (cone and rod) cells, meaning that, in order for vision to be restored, the photoreceptors themselves must be healthy. Scientists are working on replacing photoreceptors with stem cells, but until that becomes possible in humans, stem cell treatment will be limited to restoring RPE health.

For an audio-visual presentation about stem cell therapy and the London Project, go to Understanding Stem Cells in the MD Support Library.

PRIMARY SOURCE: Nature Biotechnology 

Vision loss influences sound perception

People with severe vision loss can less accurately judge the distance of nearby sounds, potentially putting them more at risk of injury, according to new research published in the journal Scientific Reports.

Researchers from Anglia Ruskin University’s Vision and Eye Research Institute (VERI) tested participants with different levels of vision loss, presenting them with speech, music and noise stimuli, and different levels of reverberation (echoes).

Participants were asked to judge the distance of the different sounds, as well as the size of the room.

People with severe visual loss judged closer sounds more inaccurately compared to those whose vision loss is less severe, who in turn, were less accurate when compared to people with normal sight. 

For more distant sounds, people with severe visual loss judged these to be twice as far away when compared to normal sighted individuals. Participants with severe sight loss also judged the rooms to be three times larger than the control group of normal sighted individuals. 

Professor Shahina Pardhan, Director of VERI, said: “Vision loss means people rely more on their hearing for awareness and safety, communication and interaction, but it was not known how hearing is affected by the severity of partial vision loss.

“The results demonstrate that full blindness is not necessary for judged auditory distance and room size to be affected by visual loss, and that changes in auditory perception are systematic and related to the severity of visual loss.

“Our research found that more severely visually impaired people were less accurate in judging the distance of closer sounds, which may make it harder for them in real-life situations, for example such as crossing busy streets.”

SOURCE: Press Release

New Bionic Eye Research

A article in the journal Nature has reported that scientists from Hong Kong and the U.S. have taken a big step toward development of a true bionic eye, more precisely called a “biomimetic electrochemical eye”.

Attempts that set it apart from other such efforts, such as the Argus 2 device, are its similarity to many of the components of the human eye:

  • At its core is the high-density array of photosensors that mimics the human retina’s photoreceptor cells.
  • Attached to each photosensor are tiny flexible wires which transmit light signals to external circuitry for processing. These mimic the nerve fibers that connect the human eye to the brain.
  • A lens and an artificial iris are positioned at the front of the device, and a spherical shell covers the components, forming the “eyeball”. The chamber within the shell is lined with a tungsten film and filled with an ionic liquid that supports the electrochemical process. This is similar to the vitreous fluid in the human eye, but it serves a different purpose.

The device, due to its spherical shape, allows a field of view of 100°, which is close to that of the human eye. Other sensory capabilities that compare favorably are:

  • Sensitivity to a wide range of light intensities
  • Quick photoreceptor recovery time
  • High density of photosensors possible, due to the device’s curved surface

This is promising research, which has yet to see resolution of certain issues:

  • The photosensor array output is still too small at only 100 pixels.
  • Fabrication costs are very high.
  • The diameter of the wires needs to be greatly reduced from ~700 to only a few micrometres.
  • The functional lifetime of the components has yet to be determined.
  • Further optimization of the ionic-liquid composition is needed.

Application to robotics will likely be the first use for this device, but the researchers are hopeful that it might be ready for humans within a decade.

SOURCE: Nature 581, 264-265 (2020) doi: 10.1038/d41586-020-01420-7

Important Message to Eye Care Patients Regarding the COVID-19 Pandemic

Reprinted from Prevent Blindness

For everyone’s health and safety, ophthalmologists, optometrists, and other doctors are being urged to see patients only for urgent or emergent problems during the coronavirus pandemic.

This is important for two reasons:

  • To limit contact between patients and staff in offices, waiting rooms, exams rooms, and surgical facilities to reduce the spread of the coronavirus;
  • To conserve vital disposable medical supplies (like masks, gloves, face shields, and sanitizing wipes, etc.) so they can be used in hospitals where they are most needed right now.

“Urgent care” is defined as medical care provided for illnesses or injuries that require prompt attention but are typically not of such seriousness as to require the services of an emergency room. “Emergency care” is defined as medical care for conditions requiring prompt medical attention due to a sudden change in the eye or visual health.  If you’re uncertain whether or not your condition is urgent or emergent, contact your eye care provider (ophthalmologist or optometrist) immediately.

You will likely find that routine patient visits, such as annual dilated eye exams, exams for glasses, and general eye health check-ups, will be rescheduled likely for a few months. Any non-emergent or non-urgent eye surgeries and procedures, for example cataract surgery, will also be postponed.  Urgent and emergent situations may include exams, treatments, and surgeries for eye injuries, retinal detachments, and other eye problems resulting in acute vision loss that may be permanent if not treated sooner. Contact your eye care provider’s office BEFORE traveling to the office to check whether your appointment is cancelled or not.

Plan ahead. If your appointment will still occur, talk to the eye care provider’s office by phone about any safety precautions you should take for the visit. In addition, please let the office know if you have a cough or a fever, or have been in close contact with someone who has these symptoms. Offices have implemented screening and cleaning procedures to preserve the health and safety of the office staff and patients who needed to be seen.

Call your eye care provider for guidance in the following situations:

  • You have an eye disease (such as macular degeneration or diabetes-related retinopathy) and receive regular eye injections;
  • You have any vision treatments that are routinely applied at the eye care provider’s office, and you are uncertain whether these are considered urgent care;
  • You suddenly lose or notice changes in your vision (such as blurred vision, wavy areas of vision, or blank spots in your field of vision);
  • You notice a lot of new floaters or flashes of light in your vision;
  • You have eye pain, headache, red eye, nausea, and vomiting.

Clinical trials

If you are currently involved in a clinical trial for a vision treatment or therapy, the FDA has encouraged all trials to consider patients’ safety when making determinations about trial recruitment and continued participation and drug administration. Changes to the conduct of each trial and the participation of its patients will depend on the various circumstances of the trial, including the nature of the disease being studied and the drug being administered, potential changes in the product’s supply chain, the regions where the trial is conducted, and more.

Contact your clinical trial site to determine what steps they are taking to ensure your safety and continuity of eye care during this time. This may include changes to how the clinical trial maintains contact with you or how treatments are administered.

For more information on Corona Virus Eye Safety, visit the resources available through the American Academy of Ophthalmology and/or the American Optometric Association.

More Ideas For Keeping Busy

In March, we posted an article which suggested ways to keep busy in spite of low vision. As we continue through another month of mass quarantine, here are more suggestions contributed by an especially thoughtful reader in response to that article.

  1. Learn a language. Duolingo, a method used in the school system, can be downloaded from the Internet.
  2. Get outdoors. In order to maintain social distancing, go to places that are not occupied by many others.
  3. Put on some music, and dance.
  4. Prepare a special meal, and dine in as if you’re dining out.
  5. Plan your next trip.
  6. Order a craft kit from Amazon.
  7. Broaden your mind. “The Great Courses” comes in a variety of formats on numerous subjects.
  8. This is a good time to introduce fully sighted friends to strategies we practice every day. For example, they may not know of how to arrange for grocery pick up.
  9. Call someone. Especially those who have had busy lives and are now isolated themselves.
  10. Give parents a break by chatting or playing games with their children through FaceTime or Zoom. Or have them give you a concert of their music pieces.
  11. Volunteer as an online teacher or tutor.
  12. Learn how to meditate.

Our thanks to Sharon Noseworthy for these excellent additions to our collection. And finally, this thought from another reader, Jean Gould:

“I think it might make sense to also remind people of what they already have at hand—especially nature and the outdoors. Just now, the blessings of spring surround us: longer days, crisp air, new fragrances. Even the simple aftermath of spring rain can be joyful and doesn’t require ‘keeping busy’, just being aware.”

Dan Roberts, Editor-in-Chief
Living Well With Low Vision

Photoreceptors From Skin Cells a Possibility

Photoreceptors are cells in the retina which convert light into nerve impulses. Because of them, we can see the world around us. The two types of photoreceptors are rod cells and cone cells. Rod cells are responsible for peripheral and night vision, and cone cells are responsible for central and color vision under bright conditions.

Science has been looking at stem cells as a possible replacement for degenerated photoreceptors, but new research reported in the April 2020 issue of Nature has shown that rod cells can also be grown from skin cells, specifically, fibroblasts, the principal active cells of connective tissue. Researchers at the University of North Texas bathed fibroblasts of mice with a set of five small molecules to chemically induce the transformation of fibroblasts into rod photoreceptor-like cells.

The transplantation of these cells into the subretinal space of rod-degenerated mice led to partial restoration of the pupil reflex and visual function. Within a month, six of 14 (43%) showed a significant reaction to low light compared to none of the untreated mice. And at three months, further examination confirmed not only the survival of the new photoreceptors, but their growth of connections (synapses) to surrounding cells.

This is important research in view of the fact that it may allow scientists to bypass the use of stem cells in growing new photoreceptors, considerably shortening the wait for future clinical therapy of retinal diseases like macular degeneration, diabetic retinopathy, and retinitis pigmentosa.

Further research with animal models is necessary before applying the protocol to humans. This will be conducted by CIRC Therapeutics, a start-up company that plans to commercialize treatments using the technology.

SOURCE: Mahato, B., Kaya, K.D., Fan, Y. et al. Pharmacologic fibroblast reprogramming into photoreceptors restores vision. Nature (2020). https://doi.org/10.1038/s41586-020-2201-4

Prima System implant has positive results in dry AMD

Pixium Vision reports that follow-up from 18 to 24 months after implantation showed that their PRIMA Bionic Vision System sustainably elicited light perception in all four dry AMD patients with favorable safety profile. Moreover, the second-generation transparent glasses, enabling to combine natural peripheral vision and prosthetic vision, greatly benefited patients and their visual acuity by 3 to 7 lines.

“The Prima System has demonstrated excellent results in improvement of visual acuity in this study and which have not been previously demonstrated in this patient population. A 3-line improvement can mean the difference between recognizing or not recognizing the letters on a street sign, and so these data reinforce the potential to make a significant difference to the lives of patients,” said Dr. Yannick le Mer, the surgeon who implanted the Prima System patients in the study. Dr. le Mer is head of the Vitreo-retinal Unit at Fondation Adolphe de Rothschild Hospital in Paris and a scientific advisor to Pixium Vision.

Based on these positive data the Prima System will be tested in PRIMAvera, the pivotal trial designed to provide the safety and efficacy data required for filing marketing authorization applications in the U.S., Europe and other parts of the world.

To read about all research and developments related to dry AMD, visit A Guide to Research In Dry AMD on this site.

SOURCE: GlobeNewswire

Visual effects reported from first human artificial retina

Nano Retina has announced preliminary results for first-in-human implantation of its NR600 artificial retina device. The first two patients to receive the device in March 2020 reported visual effect.

The NR600 mimics the natural physiological processes of the human eye and restores functional vision to persons blinded by retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa.

As part of a European multicenter clinical trial enrolling up to 20 patients for the purpose of obtaining CE approval of the NR600, the first two patients, blinded by retinitis pigmentosa, underwent the minimally invasive procedure to implant the device. The procedures were both performed in the Department of Ophthalmology of the University Hospital Leuven, Belgium, by Professor Peter Stalmans, one of Europe’s leading retina specialists. 

Following activation of the device, both patients reported visual effects, which Nano Retina expects to optimize over the coming months. As regards the second patient to receive the device, Professor Stalmans stated: “The device was activated for the first time, and the result was amazing: this patient has been completely in the dark for 5 years now, and she immediately reported seeing an image in the center of her visual field when the device was activated, and could show with her hands the size of the image that she saw. I am very impressed by this experience. I have been working for more than 20 years as an ophthalmologist, but this is the first time I witnessed a completely blind patient being given back a visual perception.” 

SOURCE: Press release

Where Are We Now?

A Summary of a Quarter-Century of Low Vision Research and Development

Presented to the International Low Vision Support Group
by Dan Roberts, Director

Macular Degeneration Support, the charitable parent corporation of our International Low Vision Support Group, is celebrating its 25th year as a leading resource for people affected by macular degeneration and similar diseases leading to central vision loss. The organization posted its first annual “Summary of Research and Development” in a June 2006 newsletter to members of its then fledgling International Low Vision Support Group. 

To put the past quarter-century of progress in perspective, this presentation revisits those early headlines and follows each with the most recent information available. The line of breakthroughs and successes has, however, not gone unbroken, so the presentation will also include mention of studies and therapies that were not able to meet expectations. Then, to finish on a positive note, highlights of the exciting field of low vision technology will be shared. 

The most notable development of this past 25 years was FDA approval of a safe and effective treatment for neovascularization, or growth of new blood vessels, which once caused quick and irretrievable central blindness in thousands of people with macular degeneration, diabetic retinopathy, diabetic macular edema, and degenerative myopia.  And that is where this review of headlines begins.

An article in December 2004, titled “Macugen Approved For Treatment of Wet AMD” announced that “a large trial of Macugen (pegaptanib sodium) on 1,196 patients at 117 centers around the world was completed in 2003 and will be available in clinics in 2005. Data showed that Macugen stabilized or improved vision in 33% of the patients in the trials, while the same results occurred in 23% of a control group not given Macugen…”

And a little more than a year later, another headline revealed that “Lucentis Maintained or Improved Vision in Approximately 95% of Patients in [a] Phase III Study.”This was a huge step forward as “Genentech, Inc. announced positive one-year results from its second pivotal Phase III study of their investigational drug Lucentis . . . in patients with wet age-related macular degeneration (AMD).”

Lucentis was approved in 2006 for treatment of wet AMD, far-outpacing Macugen as the standard of care. Since then, it has also been approved for treatment of diabetic retinopathy, diabetic macular edema, myopic choroidal neovascularization, and macular edema following retinal vein occlusion. It is one of four drugs that are now available for treatment of neovascular eye diseases, the others being Macugen (2005), off-label Avastin (2005), Eylea (2011), and Beovu (2019). And with each new product, improvements in extended release up to 12 weeks between injections are indicated.

Science has worked for over 3 decades to find the most effective methods for treating neovascularization in the retina. In the 90’s and into the beginning of the century, two laser surgeries were the only viable options. Thermal coagulation required a hot laser to seal off leaking vessels, and photodynamic therapy incorporated a lower-power laser that activates an injected drug to coagulate leaking vessels when exposed to light. Both laser treatments are still used today, but only if necessary or in combination with drug therapies. 

Taking the place of laser surgery has been development of medication that blocks vascular endothelial growth factor (VEGF), a protein produced by the body that stimulates formation of blood vessels. This “anti-VEGF” therapy goes a step further than just coagulating blood vessels. Injected into the eye, it actually halts the growth of those vessels in the first place.

And then there are combination drug therapies, which are designed to accompany anti-VEGF therapy to improve or prolong results. Most recently, Genentech’s Faricimab has been tested in combination with their anti-VEGF drug Lucentis. Another drug, Alimera Sciences’ Iluvian, a corticosteroid implant, demonstrated effectiveness in the treatment of neovascular diabetic retinopathy, but concerns by the FDA about safety and manufacturing standards have slowed its progress toward clinical trials.

Efforts are also being made to develop methods of automatic sustained release of drugs in the eye. For example, an implant called NT- 501 uses encapsulated cell technology (ECT) to manufacture and secrete a drug into the interior of the eye. In a 2012 study, NT-501 implants produced a chemical consistently over a 2-year period, but trials are currently stalled. The NT-501 is one of three sustained-release implantable drug delivery devices, the others being Retisert and Ozurdex, all of which could someday greatly relieve the burden of frequent injections.

And now new research has shown that some people may not need to undergo injections forever. A study concluded in 2019 suggested that some patients with wet AMD can actually retain good visual acuity with no treatment for at least 3 years after stopping anti-VEGF treatment. Further research may be able to identify characteristics in those patients who demonstrate higher visual acuity after cessation of injections. 

Finally, several other alternatives to a needle in the eye are being considered, such as a port delivery system, oral medications, and eye drop formulations.

With all of the understandable excitement caused by the new anti-VEGF treatments during recent years, news about wet AMD has overshadowed developments in the fight against the dry form of macular degeneration.  Now, however, dry AMD, more specifically in the advanced stage of geographic atrophy (GA) is also making headlines. 

Back in February 2006, an article titled “Statins and AMD” announced that researchers had found high doses of statins (which are cholesterol-lowering medications) to be effective at reducing the number of soft drusen deposits in retinas of people with dry AMD.

Drusen are those cellular waste deposits in the retina that have been associated with AMD. A June 2006 report titled, “Drusen Fragments May Lead to Wet AMD”, discussed whether the components of the deposits cause progression to the advanced form of AMD. After several studies through the years, it is now known that, even though drusen are associated with wet AMD, they do not actually cause it. They are, rather, a result of the disease progression. This is evidenced by attempts at removing the deposits with lasers, which has been successful, but with no resultant improvement in the patient’s condition.

Today, scientists are still in agreement that inflammation is a direct result of cholesterol buildup. They also agree that if inflammation can be reduced with statin drugs, such drugs may turn out to be effective at slowing drusen formation in AMD, treating proliferative vitreoretinal diseases, slowing the loss of acuity in diabetic retinopathy, and reducing the risk of open-angle glaucoma. Since, however, statins may carry unwanted side effects, scientists are weighing those risks with the benefits to the retina, and considering if other anti-inflammatories, such as aspirin, might be just as effective.

Many drugs have been tested for inhibition of the body’s complement system, which is part of the immune system, now widely known to be a principal factor in developing dry AMD. Apellis Pharmaceutical’s APL-2 was the first complement inhibitor tested since 2007 in patients with dry AMD, also called “geographic atrophy”. The company is currently running Phase 3 studies to assess the efficacy and safety of multiple intravitreal injections of APL-2.

Three other clinical trials are also in progress. They are Allergan’s Ozurdex implant containing brimonidine, the University of Virginia’s TOGA study evaluating low dose oral doxycycline, and Genentech’s GALLEGO study evaluating the safety, tolerability, and efficacy of intravitreal injections of a compound assigned the unwieldy name RO7171009.

“No Association Between Cataracts and Macular Degeneration” was the heading of a May 2006 report about analyses of data from the Age Related Eye Disease Study (AREDS) showing “no clear evidence of an association between cataract surgery and neovascular AMD”, and that “most patients undergoing cataract surgery can probably be reassured that surgery will not markedly increase their risk for progression to neovascular AMD”. 

Since that report, most retinal surgeons have agreed that there is minimal danger of retinal complications from such surgery in the hands of experienced practitioners. Most recently, Emily Chew, MD, reported that, after reviewing patient follow-up data from her AREDS research, “The frequency of [wet] AMD, geographic atrophy, and central geographic atrophy did not differ between patients who had cataract surgery and those who did not.”

Also in May 2006, and article titled “New Lutein Findings” contradicted earlier conclusions that the dietary carotenoids lutein and zeaxanthin are protective against the progression of AMD. “The Melbourne Collaborative Cohort Study presented evidence…that neither of the substances are protective against the disease”.

This, however, was countered by an article the very next month titled: “AREDS Formula Revised”. It announced that a second age-related eye disease study was in planning stages to include not only lutein and zeaxanthin, but to lower the amount of zinc, eliminate beta-carotene, and include DHA/Omega 3 (fish oil).

So, in spite of some early conflicting data, lutein and zeaxanthin have replaced beta-carotene in the revised formula, called AREDS-2. Fish oil, however, has not been included. 

The replacement of beta-carotene in the AREDS-2 formula resulted in a smaller decrease in the risk of progression to advanced AMD, but the revised formula is still recommended for people in the intermediate stage. The dosage of zinc has remained the same, but some supplement manufacturers have opted to lower it in their products to address digestive problems experienced by some users.

On another front, a June 2006 article, “Blue Light Risk”, reported research from the University of Chicago confirming that “the blue light wavelength peaking at 440 nanometers causes retinal damage through photochemical change and [programmed] cell death.” 

This research was done with animals’ eyes, but no trials have yet been, and probably won’t be, accomplished to confirm the findings in humans. The opinions, therefore, are split fairly evenly between risk and no-risk, leaving it up to the individual to decide if precautions should be taken.  

A recent surge in marketing for blue-light-filtering lenses has kept the issue alive, particularly in connection with the use of electronic devices with screens. The sun, and full spectrum lamps which imitate the sun, are the two strongest and most common sources of blue light. Blue light intensity from screens is much less than either of those sources, so most experts agree that individuals who are concerned about exposure to digital screens might simply follow sensible practices like limiting screen time, taking periodic breaks, and taking advantage of light-filtering options.

Another May 2006 article announced that “Ocular coherence tomography [is] useful in determining [the] need for Lucentis treatment”, revealing that “a study by the Bascom Palmer Eye Institute, University of Miami, was evaluating the use of optical coherence tomography (OCT) for determining when patients needed an injection of Lucentis . . .”

OCT has since become the gold standard for diagnosing retinal disease, surpassing fluorescein angiography (FA) as the most common diagnostic procedure. And now, ocular coherence tomography angiography (OCTA) has combined both technologies by producing side views of the retinal layers alongside frontal imaging. Like the original OCT, OCTA requires neither dye injections nor uncomfortable camera flashes, so not only are patients happier, but frequent and better imaging is possible, making the doctors’ assessments more precise.

Treatment for wet AMD has indeed been a hot news topic since the early 2000’s, but two therapies have been developing in tandem with that research which could someday make treatment unnecessary. Those are gene replacement therapy and stem cell therapy, both of which could bring a cure for vision impairment and blindness.

A headline in January 2006 declared that “Gene Replacement Therapy [was] Successful in Early Trials.” Researchers at Johns Hopkins University Medical Center used gene replacement therapy to halt, at least temporarily, retinal bleeding in patients with wet AMD. That was done by injecting a PEDF (pigment epithelial derived factor) gene into the eyes of patients during a phase I clinical trial.

That work, and other work like it, led to successful delivery in December 2017 of a normal gene to replace a defective gene in three young patients with Leber congenital amaurosis, leading the way to potential gene replacement therapy for other retinal diseases. In view of the initial success, scientists became enthused about studying how genetic variants play a part in AMD. Retina gene therapy clinical trials are currently testing more than 1,150 patients enrolled at more than 30 sites to determine how AMD genes relate to development of the disease and to look for targets for new treatment strategies.

For example, a preliminary study last October showed that patients with wet AMD had long-term vision stabilization and anatomic improvement following a single injection of RGX-314, an investigational gene therapy.

Three of six study participants showed sustained benefit from a single injection of RGX-314 for more than 1.5 years. And in another cohort with shorter follow-up, nine of 12 patients remained free of rescue medication for up to 6 months.

The excitement caused  by headlines such as “Stem Cells Promise Cure”, back in April 2006, may have been a bit premature. The author wrote, “Stem cell transplantation is showing promise as a potential cure for retinal disease…significant improvement has been noticed in vision of the patients after one month of injecting stem cells. There is further improvement after a gap of three months”. Stem cell replacement may someday soon restore vision after a single visit to the clinic, but there is still much work to be done to ensure a safe outcome. And the work is proceeding.

Results from several clinical trials have added support for the use of human embryonic stem cells as treatment for the dry form of macular degeneration. Stem cells injected into the eye appear to be replacing missing cells damaged by the disease, with no serious side effects, and they are even improving patients’ vision. 

A National Eye Institute (NEI) study will soon test the safety of a stem cell treatment for dry AMD, in which the researchers will take a patient’s own blood cells and convert them into stem cells that can be programmed to become retinal pigment epithelial (RPE) cells, which nourish the photoreceptor sight cells. These RPE cells are then grown in sheets one cell thick on a biodegradable scaffold and inserted into the retina. The expectation is that they will replace and nourish the lost cells and restore sight.

Researchers continue to look for sources of stem cells other than embryos. Newly-discovered sources are bone marrow, brain tissue, umbilical cord blood, amniotic fluid, and even the patients’ own skin and eyelids.

Meanwhile, patients are being warned about companies that are making unsubstantiated claims about stem cell “cures”. At this time, no stem cell treatments for retinal diseases have been approved for clinical use by the FDA, and anyone considering participation in a clinical trial should ask if the FDA has reviewed the treatment. An honest health care provider would be able to confirm this information by providing a New Drug Application (NDA) number and the chance to review the FDA communication approving its experimental use. Patients should ask for this information before getting treatment, even if the stem cells are their own.

These headlines have focused mostly on the positive developments in retinal research. Disappointingly, not all expenditures of time and money have succeeded in bringing better treatments into the clinic. Some famous studies and procedures that have been suspended or cancelled, or that have simply not yielded encouraging results over the past quarter-century, are retinal transplantation, transpupillary thermotherapy, radiation therapy, rheopheresis therapy, and drusen lasering.

Advancement in low vision technology, however, has been nothing less than miraculous for such a relatively brief period of time, with developments such as:

  • Desktop electronic magnifiers (CCTVs) for displaying enlarged and enhanced text onto a screen.
  • Portable hand-held electronic magnifiers, which are essentially small battery-operated versions of CCTVs.
  • Bioptic glasses, which are small binoculars built into the top of prescription glasses allowing for periodic distance viewing while driving.
  • Optical character recognition systems, which can read text and hand writing aloud.
  • Portable way-finding systems for navigating unfamiliar environments outdoors or indoors.
  • Voice operation of computers, smart phones, and appliances
  • Artificial intelligence (AI) applications for identifying the environment and recognizing people.
  • A miniature telescope implanted into one eye, allowing constant hands-free magnification.
  • Head-worn electronic vision enhancement systems for adjustable magnification and improvement of clarity, brightness, and contrast.
  • Currency and color identification devices, available separately or as smart phone applications.
  • Devices for self-monitoring vision changes.
  • Expansion of built-in accessibility features on smart phones and computers providing text enlargement, text-reading, and zoom capabilities.

Finally, the growth of the Internet since the 1990’s has given low vision people unlimited access to the information and support they need to manage their lives successfully. Through such formats as email discussion groups, message boards, social media platforms, webcasts, podcasts, and news blogs, people are sharing and learning to an extent never-before possible.

Sometimes, it seems that things are not moving fast enough toward  treatments and cures. Impatience  is understandable when viewed within the limits of a single lifetime. But when viewed through the wider lens of history, the progress since the turn of this century has been immense and the expansion of knowledge has been exponential.

The ironically-named 2020’s will see the culmination of a great deal of research that first saw light during this past 25 years. The massive amount of work in pharmacology, surgery, and technology will begin to coalesce into treatments, cures, and assistive media leading to a world virtually without blindness. Being on hand to personally witness, and to be a part of this unique time in history, is a privilege for patients and professionals alike. And the honors go to men and women who are continuing to press forward for the benefit of those yet to come.          

NIH researchers discover tooth-enamel protein in eyes with dry AMD

Information from the National Eye Institute

A protein that normally deposits mineralized calcium in tooth enamel may also be responsible for calcium deposits in the back of the eye in people with dry age-related macular degeneration (AMD), according to a study from researchers at the National Eye Institute (NEI). This protein, amelotin, may turn out to be a therapeutic target for the blinding disease. The findings were published in the journal Translational Research. NEI is part of the National Institutes of Health.

“Using a simple cell culture model of retinal pigment epithelial cells, we were able to show that amelotin gets turned on by a certain kind of stress and causes formation of a particular kind of calcium deposit also seen in bones and teeth. When we looked in human donor eyes with dry AMD, we saw the same thing,” said Graeme Wistow, Ph.D., chief of the NEI Section on Molecular Structure and Functional Genomics, and senior author of the study.

Recently, researchers found a calcium-containing mineral compound called hydroxyapatite (HAP) in dry AMD drusen-like deposits. HAP is a key component of tooth enamel and bone. Small balls of HAP filled with cholesterol, called spherules, were found in drusen only from people with dry AMD, and not in those with wet AMD or without AMD. Wistow’s team discovered that if they starved RPE cells, the cells began to deposit HAP.  They determined that the protein amelotin, encoded by the gene AMTN, is strongly activated after extended starvation and is responsible for the mineralization of HAP. Blocking the genetic pathway in their RPE cell line blocked the production of these deposits.

Why RPE cells in dry AMD begin depositing these HAP spherules is unclear, but Wistow thinks it may be a protective mechanism gone awry. It’s possible, he says, that these protein, lipid, and mineral deposits may help damaged RPE cells block blood vessels from growing into the retina, a problem that is one of the key features of wet AMD. But when the mineral deposits get too extensive, they may also block nutrient flow to the RPE and photoreceptors, leading to retinal cell death.

“Mechanistically, amelotin looks like a key player for the formation of these very specific hydroxyapatite spherules. That’s what it does in the teeth, and here it is in the back of the eye. Conceptually, you could see coming up with drugs that specifically block the function of amelotin in eye, and this might delay the progression of the disease. But we won’t know until we try it,” said Wistow.

Reference:

Rajapakse D, Peterson K, Mishra S, Fan J, Lerner J, Campos M, and Wistow G. “Amelotin is expressed in retinal pigment epithelium and localizes to hydroxyapatite deposits in dry age-related macular degeneration.” Translational Research. 2020. doi: 10.1016/j.trsl.2020.02.007

Beovu Safety Under Investigation

Patients who are undergoing anti-VEGF treatment with Beovu (brolucizumab) for wet AMD should be aware that the drug is currently being investigated by the drug’s manufacturer, Novartis, for potential adverse events in some patients. 

Beovu was approved for clinical use in October 2019, and it has since shown to be an effective and long-lasting inhibitor of blood vessel development (neovascularization) in the retina. Two known adverse events, however, are of particular concern to some practitioners. Cases of intraocular inflammation (vasculitis) and retinal artery occlusion, which occurred in 4% and 1% of trial subjects respectively, are now showing up in a concerning number of patients in the clinics. For that reason, Novartis is conducting a comprehensive review of the drug and is gathering pertinent clinical data from practitioners.

Meanwhile, patients are being advised to contact their doctors for treatment if they experience signs of inflammation or diminished vision after Beovu injection. Doctors are also being advised to ensure that no inflammation is present in the eyes of patients prior to injection. In such events, injections should be withheld until the condition has been treated.

For more information visit novartis.com.

Some Wet AMD Patients May Not Need Injections Forever

A study concluded in 2019 suggests that some patients with wet AMD can retain good visual acuity with no treatment for at least 3 years after stopping anti-VEGF treatment.

Researchers compared two groups from the 2008-2009 Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). The first group was comprised of patients who had been released from the trial protocol and received no further treatment. The second group was defined as those who continued receiving treatment through the trial.

The visual acuities of the two groups 3 years after the initial 2 years of treatment, mean visual acuity score on the Snellen chart was 20/25 for 45% of the first group compared to a score of 20/80 for the second group. Further research may identify characteristics that might be associated with higher visual acuity in some people following cessation of treatment. So even though the reason for the difference has not yet been identified, the research offers some basis for hope that not all eyes with wet AMD may need treatment forever.

SOURCE: 

Characteristics of Eyes With Good Visual Acuity at 5 Years After Initiation of Treatment for Age-Related Macular Degeneration but Not Receiving Treatment From Years 3 to 5: Post Hoc Analysis of the CATT Randomized Clinical Trial. Drew Scoles, MD, PhD et al (JAMA Ophthalmol. Published online January 30, 2020. doi:10.1001/jamaophthalmol.2019.5831)

ClinicalTrials.gov Identifier: NCT00593450

Anti-scarring angiogenic drug enters Phase 2

RIBOMIC, Inc. has announced that the first patient has received injection in the phase 2 trial of RBM-007 for the treatment of exudative age-related macular degeneration (AMD) in the United States. The first site started enrollment at the end of December 2019 and five sites are now active across the United States.

Currently approved therapies for wet AMD, intravitreal injections of anti-VEGF drugs, have shown dramatic visual benefits for wet AMD patients. A significant portion of these patients, however, exhibit incomplete response to therapy, and over the extended management course can lose vision, with the formation of submacular fibrosis (scarring) as one risk factor.

RBM-007 is a dual-action drug designed to block blood vessel growth (angiogenesis) and to block fibroblast growth factor 2 (FGF2), which causes scarring. This holds promise as an additive or alternative therapy to anti-VEGF treatments for wet AMD.

A Phase 2 Study assessing the safety, efficacy and durability of RBM-007 is underway. For information about the trial, see: https://clinicaltrials.gov/ct2/show/NCT04200248

Source: Businesswire.com

“How long will my anti-VEGF drug therapy be effective?”

This is becoming a common question among people who have been treated for years with anti-VEGF drug therapy. These eye injections are the gold standard for treatment of wet age-related macular degeneration (wAMD), having been first used clinically in 2004.

The news is good. A recent retrospective review in the U.K. has found that almost 50% of eyes with wAMD continued to be stable or improved after 8 years of treatment with Lucentis (ranibizumab). This compares favorably with other similar studies in the U.S., Belgium, and Australia. 86 patients, average age 72, were injected a mean total of 31.6 times during the 8 years, which included 3 initial loading doses and treatment as needed thereafter. Half of the patients needed yearly injections, and a quarter of the patients were able to stop injections for a year or more due to achieving stability.

As expected, due to the underlying effects of the disease, about 34% of the patients lost up to 15 letters of acuity, but nearly 50% of eyes had maintained or even improved vision. In other words, the effectiveness of anti-VEGF treatment may not have a time limit. And if a patient does become resistant to a particular drug, practitioners have had success, other than in rare cases) with switching to another of the four leading products: Lucentis, Eylea, Beovu, and off-label Avastin.  

The research team concluded that the results of this study could serve as “useful, relevant information” in counseling wAMD patients about their expectations. And patients can take comfort in knowing that they are protected well into the future.

SOURCE:

Real-World Visual And Clinical Outcomes For Patients With Neovascular Age-Related Macular Degeneration Treated With Intravitreal Ranibizumab: An 8-Year Observational Cohort (AMD8) by Horner F. et al . (Clin Ophthalmol 2019;13:2461-2467.)

New discovery may lead to AMD treatment

Researchers have discovered a protein that might be related to the cause of age-related macular degeneration (AMD) and thus provide insight into early diagnosis and treatment. The study, published in Nature Communications, was a collaboration of Queen Mary University of London, the University of Manchester, Cardiff University, and Radboud University Medical Center, Nijmegen.

High levels of the H-related protein 4 (FHR-4) were found in the blood and in donated macular tissue of 484 patients with AMD. FHR-4 is an important regulator of the complement (immune) system, which causes inflammation. If uncontrolled, inflammation is a major factor in degeneration of macular tissue. By targeting that particular gene, therefore, and/or by reducing blood levels of FHR-4, the discovery could lead to a yet-unavailable treatment for the disease.

SOURCE: Cipriani, V., Lorés-Motta, L., He, F. et al. Increased circulating levels of Factor H-Related Protein 4 are strongly associated with age-related macular degeneration. Nat Commun 11, 778 (2020). https://doi.org/10.1038/s41467-020-14499-3 

Smoking Is At An All-Time Low

For over two decades, eye health organizations have worked diligently to increase awareness of the high risks of macular degeneration from tobacco smoking. Now, the recently-released 2020 Surgeon General’s report has revealed that the work of those organizations is paying off.

Americans are doing better at making good choices when it comes to smoking. According to latest research, the percentage of Americans who smoke has decreased to an all-time low of 14%, or 34 million people. More than three out of every five adults (61.7%) who were ever cigarette smokers have quit, with credit being given to better education, improved health care, availability of effective smoking cessation treatments, aggressive media campaigns, and encouragement of warning labels on tobacco products.

The SG report also found that persons who had smoking-related chronic diseases like macular degeneration were more likely to heed professional advice to quit than those without the disease. This may be because such persons have more contact with healthcare and patient support systems, or simply because they realize that quitting could improve, or avoid exacerbating, their eye condition and general health.

Whatever the reasons for quitting or never starting smoking, this news is good. Unfortunately, the research has shown that, with increasing age, attempts to give up tobacco tend to decrease. If only for that reason, awareness efforts and patient support need to continue as long as the temptation exists.

SOURCE: U.S. Department of Health and Human Services. Smoking Cessation. A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2020.

How Do They Come Up With Those Drug Names?

Macugen. Lucentis. Avastin. Eylea. Beovu.

All of those are anti-VEGF drugs prescribed for treatment of wet AMD and other conditions involving growth and leakage of new blood vessels in the retina. Those brand names appear in articles and ads, but rarely in eye specialists’ notes and prescription orders. Such names are designed mainly for public use, as they are easier to remember and spell than their professional generic names. Respectively, the generic names for the above drugs are:

pegaptanib. ranibizumab. aflibercept. bevacizumab. brolucizumab.

(Notice that generic names are not capitalized, while brand names are.)

A drug’s generic name must be assigned and approved by the United States Adopted Names Council (USAN) and the World Health Organization (WHO). The name must be clear and concise, and it may be similar to related drugs to assist in its identification. For example, word endings common to anti-VEGF drugs are “-anib”, “-bercept”, and “-umab”. Letters in the middle of the name can also carry a message, like “-ci”, meaning that the drug targets the circulatory system. Sometimes, the prefix may also have something to tell. “Peg-” at the beginning, for instance, means that a substance in the drug has added polyethylene glycol. Generally, though, prefixes mean nothing. They serve simply to differentiate one drug from another.

So generic names for drugs are meaningful to professionals and are well-regulated globally. Brand names, however, need not follow rules other than being memorable and sounding appropriate. A brand name will most likely come from an ad company or a brainstorming session with a few corporate employees. It could contain an anagram, a reverse-spelling, an acronym, a word-combination, an abbreviation, or maybe even someone’s name. Some smart companies relate the name of a drug to its target treatment, which helps people remember their product by association. Latin, not surprisingly, tends to be the favored language.

How, then, did the specific brand names Macugen, Lucentis, Avastin, Eylea, and Beovu come to be? After a bit of detective work, here are some educated guesses:

Macugen: combination of “macula” (central retina) and an abbreviation of “genesis” (formation of something, e.g. blood vessels).

Lucentis: combination of “lucent” (a medical term for a pale area revealed under examination) and “centis” (Latin for “puncture”, e.g. by a syringe).

Avastin: combination of “avast” (from early Dutch “hou’vast” (“hold fast”) and “-in” (a suffix common to anti-inflammatory drugs).

Eylea: combination of “eye” (as in “eyeball”) and “lea”, derived from “lux” (Latin for “light”).

Beovu: combination of “beo” (Latin for “life”) and “vu” (Latin for “see”).

This may be of interest only to etymologists, aspiring pharmacologists, curious patients, or prospective parents looking for baby names. At the very least, it may help to explain the reasoning behind those mysterious labels.

Dan Roberts
Editor-in-Chief
Prevent Blindness

Trials to begin for stem cell-based therapy to treat geographic atrophy

A National Eye Institute (NEI) study will test the safety of a stem cell treatment for the dry (atrophic) form of age-related macular degeneration (AMD).

The researchers will take a patient’s own blood cells, and in a lab, convert them into induced pluripotent stem cells (iPSC) capable of becoming any type of cell in the body. The iPS cells are then programmed to become retinal pigment epithelial (RPE) cells, which nourish the photoreceptor sight cells.

Before they are transplanted, the iPSC-derived RPE are grown in sheets one cell thick, replicating their natural structure within the eye. This monolayer of iPSC-derived RPE is grown on a biodegradable scaffold designed to promote the integration of the cells within the retina. Surgeons position the patch between the RPE and the photoreceptors using a surgical tool designed specifically for that purpose.

Under the phase I/IIa clinical trial protocol 12 patients with advanced-stage geographic atrophy will receive the iPSC-derived RPE implant in one of their eyes and be closely monitored for a period of at least one year to confirm safety before moving into later phases.

This is the first clinical trial in the U.S. to use replacement tissues from patient-derived iPS cells. To keep up on latest research for dry (atrophic) AMD, see A Guide to Research in Dry AMD on this site.

Cognitive Decline Associated With AMD

Investigators have found significant associations between lessened brain functions and age-related macular degeneration (AMD). 5604 people age 40+ who participated in the 2005-2008 National Health and Nutrition Examination Survey have been found to experience increased memory problems and confusion, seemingly as a result of their AMD. The report was published in the December 2019 issue of the British Journal of Ophthalmology.

People with any level of AMD were found to have 1.62-fold higher odds of having self-reported cognitive difficulties compared to those without AMD. Likewise, patients with early and late AMD were associated with significantly higher reporting of memory problems.

The investigators concluded from these results that “more attention should be paid [to] the subjective memory function and potential risk of cognitive decline among patients with AMD”. Patients, meanwhile, should be aware of the importance of helping prevent memory loss through mental activity, physical conditioning, reducing stress, and maintaining brain fitness.

Until science comes up with ways to stop cells from aging, senior adults need to be extra diligent in keeping all of their faculties as sharp as possible. And for visually impaired people, memory is one of the most important. More on this topic may be heard in the 20-minute presentation, “Memory as a Substitute for Vision: The Aging Brain”, by Colleen O’Donnell, MSA, OTR, CLVT (Visual Rehabilitation and Research Center, Henry Ford Health System) .

Source abstract:  Association between age-related macular degeneration and subjective cognitive complaints. by Zhu Z, Lioa H, Scheetz J, Zhang J, He M. (Br J Ophthalmol. December 4, 2019.)

Positive Results From RGX-314 Gene Therapy

(Updated 9/10/2020)

As reported here in 2017, a drug called RGX-314 is being tested as a one-time sub-retinal injection for wet age-related macular degeneration (wAMD). A preliminary study showed that patients with wAMD had long-term vision stabilization and anatomic improvement following a single treatment with the investigational gene therapy.

Now, in a subgroup of patients with the longest follow-up, three of six showed sustained benefit from a single injection of RGX-314 for more than 1.5 years. In another cohort with shorter follow-up, nine of 12 patients remained free of rescue medication for up to 6 months.

None of 42 patients treated in five dose cohorts had drug-related serious adverse events (SAEs). The results were reported at the American Academy of Ophthalmology meeting in October 2019.

Investigation of RGX-314 with a phase IIb trial (AAVIATE) is proceeding, with dosing of the first patient using suprachoroidal delivery. REGENXBIO expects to have an interim data update from the first cohort by the end of 2020. This targeted, in-office suprachoroidal delivery of RGX-314 using the SCS Microinjector® may provide additional administration options for patients with wet AMD.

New Treatment Effective For Treatment of Dry AMD

A Phase 2 study has found that a new drug could be a safe and effective treatment for improving vision in patients with dry age-related macular degeneration (AMD).

On October 13, 2019, David Boyer, MD (Retina-Vitreous Associates Medical Group), presented results from a study of risuteganib intravitreal injection to members of the American Academy of Ophthalmology (AAO). He reported that the Phase 2 primary endpoint was met, with nearly half of those receiving the treatment achieving an increase of 8 or more letters of best-corrected visual acuity (BCVA) at 48 weeks.

A total of 45 patients were recruited for the study and 42 were included in the final analyses. A total of 25 patients were included in the risuteganib group while 14 were included in the sham group. Due to the successful results, all patients were allowed to switch over to risuteganib at week 16.

No serious systemic serious adverse events and no ocular serious events occurred as a result of risuteganib use. In addition to the study participants, 1200 injections have been given outside of the study.

For descriptions of this and other treatments for dry AMD now in clinical use and in trials, see A Guide To Research in Dry AMD

SOURCE: “Primary Results from Phase 2 Study of Risuteganib (RSG) in Intermediate Dry AMD,” presented at AAO 2019 by David Boyer, MD.

Novel Gene Therapy In Trials for Wet AMD

(Updated 10/12/19)

Adverum Biotechnologies, Inc. has announced progress with yet another therapy designed to extend the time between anti-VEGF injections for treatment of wet age-related macular degeneration (wAMD). The company’s Investigational New Drug (IND) application has been approved for a multi-center study of ADVM-022, a novel gene therapy candidate for the treatment of wAMD.

“We are excited to have this IND active for ADVM-022, currently the only intravitreal gene therapy candidate entering the clinic for patients with wet AMD,” said Leone Patterson, interim president and chief executive officer of Adverum Biotechnologies.

Results of the phase 1 OPTIC trial, reported at the meeting of the American Academy of Ophthalmology in October 2019, revealed that ADVM-022 showed the ability to maintain vision with a one-time injection and was well-tolerated, with no serious adverse events (SAEs), no dose limiting toxicities (DLTs), and no Grade 3 adverse events.

Six leading retinal centers across the United States are participating in the Phase 1 trial, with each patient being followed for a total of 2 years.

Source:
Adverum press release

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