Study advances gene therapy for glaucoma

While testing genes to treat glaucoma by reducing pressure inside the eye, University of Wisconsin-Madison scientists stumbled onto a problem: They had trouble getting efficient gene delivery to the cells that act like drains to control fluid pressure in the eye.

Genes can’t work until they enter a cell.

Glaucoma, one of the most common blinding diseases, is caused by excess pressure inside the eye, usually due to a clog in the fluid drain. “Most glaucoma can be treated with daily drug treatment,” says Paul Kaufman, professor of ophthalmology and visual sciences at the University of Wisconsin-Madison. “Replacement genes could, theoretically, restore normal fluid flow for years on end, without requiring daily self-administration of eye drops that is inconvenient and may have local or even systemic side effects.”

In a study published today in the scientific journal Investigative Ophthalmology and Visual Science, Kaufman and Curtis Brandt, a fellow professor of ophthalmology and visual sciences at UW-Madison, showed an improved tactic for delivering new genes into the drain, called the trabecular meshwork.

The colleagues have been testing a vector based on feline immunodeficiency virus (FIV) to deliver the genes. Like the related c, FIV can insert genes into the host’s DNA. The eye’s innate defenses against FIV, however, interfered with the delivery.

Virus particles contain genes wrapped in a protein coat and then a lipid membrane. After the virus enters the cell and sheds its membrane, defensive molecules from the host can “drag the virus particle to the cell’s garbage disposal, called the proteasome, where it is degraded,” Brandt says. “We wanted to know if temporarily blocking the proteasome could prevent the destruction of the gene delivery vector and enhance delivery.”

In the current study, FIV virus carrying a marker protein was placed on cells of the trabecular meshwork, with or without a chemical that blocks proteasomes.

Above a dosage threshold, the treatment roughly doubled the transfer of genes entering the target cells, Brandt says. The new genes also spread more uniformly across the meshwork tissue. Delivering more copies of the gene should give a greater therapeutic effect, opening the meshwork drain and reducing pressure inside the eye.

The present study concerns the tools for transferring genes, not the genes themselves, Brandt says. But even before the current study, he says he and Kaufman “have already identified at least two genes that could unplug the drain.”

In the long struggle to replace genes and cure disease, “eyes have been one of the big success stories,” Brandt says. A blinding eye disease called Leber’s congenital amaurosis damages the function of cells that keep the light-sensitive cells healthy; replacing the mutated genes has preserved and even improved vision in young patients. Approval for this gene therapy is now pending at the Food and Drug Administration.

To forestall danger from injecting a virus, “We take out pretty much all of the virus’ genes, so it has no chance to replicate and spread from where it’s initially injected,” says Brandt.

Although the technique does interfere with the anti-viral defense in the eye, the effect is temporary. “You encounter the drug once, then it is metabolized, and the innate inhibition is lost,” Brandt says.

“We have shown that this strategy does work in eye organ culture,” Brandt says. “Once we do further work on efficiency and identify which gene to deliver, then we are probably ready to move toward clinical trials.”

NIH Discovery Brings Stem Cell Therapy for Eye Disease Closer to the Clinic

Scientists at the National Eye Institute (NEI), part of the National Institutes of Health, report that tiny tube-like protrusions called primary cilia on cells of the retinal pigment epithelium (RPE)—a layer of cells in the back of the eye—are essential for the survival of the retina’s light-sensing photoreceptors. The discovery has advanced efforts to make stem cell-derived RPE for transplantation into patients with geographic atrophy, otherwise known as dry age-related macular degeneration (AMD), a leading cause of blindness in the U.S.  The study appears in the January 2 Cell Reports.

“We now have a better idea about how to generate and replace RPE cells, which appear to be among the first type of cells to stop working properly in AMD,” said the study’s lead investigator, Kapil Bharti, Ph.D., Stadtman Investigator at the NEI. Bharti is leading the development of patient stem cell-derived RPE for an AMD clinical trial set to launch in 2018.

In a healthy eye, RPE cells nourish and support photoreceptors, the cells that convert light into electrical signals that travel to the brain via the optic nerve. RPE cells form a layer just behind the photoreceptors. In geographic atrophy, RPE cells die, which causes photoreceptors to degenerate, leading to vision loss.

Bharti and his colleagues are hoping to halt and reverse the progression of geographic atrophy by replacing diseased RPE with lab-made RPE. The approach involves using a patient’s blood cells to generate induced-pluripotent stem cells (iPSCs), cells capable of becoming any type of cell in the body. iPSCs are grown in the laboratory and then coaxed into becoming RPE for surgical implantation.

Attempts to create functional RPE implants, however, have hit a recurring obstacle: iPSCs programmed to become RPE cells have a tendency to get developmentally stuck, said Bharti. “The cells frequently fail to mature into functional RPE capable of supporting photoreceptors. In cases where they do mature, however, RPE maturation coincides with the emergence of primary cilia on the iPSC-RPE cells.”

The researchers tested three drugs known to modulate the growth of primary cilia on iPSC-derived RPE. As predicted, the two drugs known to enhance cilia growth significantly improved the structural and functional maturation of the iPSC-derived RPE. One important characteristic of maturity observed was that the RPE cells all oriented properly, correctly forming a single, functional monolayer. The iPSC-derived RPE cell gene expression profile also resembled that of adult RPE cells. And importantly, the cells performed a crucial function of mature RPE cells: they engulfed the tips of photoreceptor outer segments, a pruning process that keeps photoreceptors working properly.

By contrast, iPSC-derived RPE cells exposed to the third drug, an inhibitor of cilia growth, demonstrated severely disrupted structure and functionality.

As further confirmation of their observations, when the researchers genetically knocked down expression of cilia protein IFT88, the iPSC-derived RPE showed severe maturation and functional defects, as confirmed by gene expression analysis. Tissue staining showed that knocking down IFT88 led to reduced iPSC-derived RPE cell density and functional polarity, i.e., cells within the RPE tissue pointed in the wrong direction.

Bharti and his group found similar results in iPSC-derived lung cells, another type of epithelial cell with primary cilia. When iPSC-derived lung cells were exposed to drugs that enhance cilia growth, immunostaining confirmed that the cells looked structurally mature.

The report suggests that primary cilia regulate the suppression of the canonical WNT pathway, a cell signaling pathway involved in embryonic development. Suppression of the WNT pathway during RPE development instructs the cells to stop dividing and to begin differentiating into adult RPE, according to the researchers.

The researchers also generated iPSC-derived RPE from a patient with ciliopathy, a disorder that causes severe vision loss due to photoreceptor degeneration. The patient’s ciliopathy was associated with mutations of cilia gene CEP290. Compared to a healthy donor, iPSC-derived RPE from the ciliopathy patient had cilia that were smaller. The patient’s iPSC-derived RPE also had maturation and functional defects similar to those with IFT88 knockdown.

Further studies in a mouse model of ciliopathy confirmed an important temporal relationship: Looking across several early development stages, the RPE defects preceded the photoreceptor degeneration, which provides additional insights into ciliopathy-induced retinal degeneration.

The study’s findings have been incorporated into the group’s protocol for making clinical-grade iPSC-derived RPE. They will also inform the development of disease models for research of AMD and other degenerative retinal diseases, Bharti said.

This work was supported by the NEI intramural research program and the NIH Common Fund’s Regenerative Medicine Program.

Scientists Find Therapeutic Target for Diabetes-Related Blindness

Study reveals single cell type and surface molecule sufficient to cause common complication

Specific cells in the retina trigger inflammation and vision impairment associated with diabetes, according to new research out of Case Western Reserve University School of Medicine. The findings unexpectedly implicate Müller cells—which provide structural support in the retina—as key drivers of the process. Researchers now have a therapeutic target in hand and understand initial steps of diabetic retinopathy, one of the most common and debilitating side effects of diabetes.

Carlos Subauste, MD, Associate Professor of Medicine and Pathology and Timothy Kern, PhD, Professor of Medicine, Ophthalmology and Pharmacology at Case Western Reserve University School of Medicine led the research, recently published in Diabetes. Said Subauste, “Our studies uncovered a novel mechanism that explains the development of experimental diabetic retinopathy. Diabetic retinopathy is the leading cause of visual impairment in working age adults in the western world.”

In the study, Subauste and his team zeroed in on a receptor protein that sits on the surface of Müller cells. They discovered the receptor, CD40, sends signals to nearby cells called microglia and macrophages to initiate harmful inflammation in the retina. But, CD40 is a regular on the surfaces of many cells, so Subauste and his team had to devise a clever strategy to determine which cells initiate the harmful chain of events.

“From studies done with Dr. Kern, we knew mice with no CD40 are protected from diabetic retinopathy,” said Subauste. “We created transgenic mice that only express CD40 on Müller cells to further examine the role of the receptor.” The researchers discovered that mice with the receptor limited to Müller cells still developed retinopathy. A closer look revealed that CD40 also elicits pro-inflammatory molecules from bystander microglia and macrophages. The researchers found that CD40 makes Müller cells secrete a small energy molecule called ATP. In turn, ATP engages a specific receptor on the surface of microglia and macrophages triggering inflammatory responses in these cells.

The researchers had found their culprit. Their study provides direct evidence that a single receptor on the surface of Müller cells is sufficient to cause harmful inflammation that leads to experimental diabetic retinopathy.

Said Subauste, “Our study identifies CD40 as a therapeutic target against diabetic retinopathy.” The prevalence of the receptor throughout the body suggests the findings may also be applicable to inflammatory bowel disease, atherosclerosis, or lupus.

“Add-back of CD40 represents an elegant means of testing the hypothesis,” said a commentary in the journal featuring the study, calling the findings “unprecedented.”
Diabetic retinopathy is a major complication of diabetes that impairs the ability of the retina to sense light. For years, scientists have implicated inflammation as a primary driver of the complication, but it has been difficult to tease apart the many cells and signal molecules involved.

Said Subauste, “The choice of Müller cells was not obvious since it would have been logical to predict that CD40 expressed on microglia, macrophages, or endothelial cells, would have been the major driver of inflammation in the retina.” Instead, the researchers discovered CD40 on Müller cells activates these cell types, which are often implicated in inflammation.

Subauste teamed up not only with Timothy Kern, PhD but also with George Dubyak, PhD, Professor of Physiology and Pharmacology at Case Western Reserve University School of Medicine for the groundbreaking study. Subauste and Kern are now combining the mouse models with pharmacologic interventions identified by Subauste that block inflammatory processes induced by CD40, to ultimately prevent diabetic retinopathy.

In-Home Occupational Therapy Curbs Depression in Visually Impaired Patients

Depression is common in patients with central vision loss, but study suggests that low vision rehabilitation and occupational therapy could decrease its severity

Johns Hopkins researchers report that in-home occupational therapy appears to reduce the rate and severity of depression in people at higher risk for the disorder because of seriously impaired vision.

The Centers for Disease Control and Prevention says older adults in the United States are already at an increased risk of depression as their health and social lives change. Vision-impairing diseases, such as age-related macular degeneration, contribute to these changes for an estimated 1.6 million Americans.

The new study, described March 8, in Investigative Ophthalmology & Visual Science, used measures obtained from the previous Low Vision Depression Prevention Trial in Age-Related Macular Degeneration (VITAL) study to conclude that low-vision patients who improve in their day-to-day functions, such as cooking, reading mail or using a computer, through at-home training with an occupational therapist have less severe symptoms of depression than similar patients who did not train with an occupational therapist.

“Our goal for this study was to see if occupational therapy was a better investment than supportive therapy in preventing depression in low-vision patients,” says Ashley Deemer, O.D., instructor of ophthalmology at the Johns Hopkins University School of Medicine.

The study was based on information originally gathered for the VITAL study at Thomas Jefferson University in Philadelphia and included data on 188 patients with age-related macular degeneration. The patients’ average age was 84, and 70.2 percent of the patients were women. The patients had an average visual acuity of 20/96, meaning that the average person in this study could see an object 20 feet away, while someone with normal vision could see the same object at 96 feet. All patients also reported borderline depressive symptoms, scoring greater than five on the Patient Health Questionnaire-9, a clinical survey used to estimate depression risk. In this survey, a score of zero is an indication that the patient has no depression or is at a low risk, and a score of 20 or higher marks a patient as at risk for severe depression.

After enrollment in the study, all patients visited a low vision rehabilitation optometrist and filled out a questionnaire designed to assess the importance and difficulty of daily activities, such as cooking, driving, pleasure reading and using a computer.

Patients were then divided into two treatment groups — an occupational therapy group and a supportive therapy group. The group of patients receiving occupational therapy met with an occupational therapist for six one-hour sessions in their homes. Utilizing tools like magnifying glasses, electronic devices and computer programs, the occupational therapist helped train patients to find new ways to achieve the tasks patients had ranked as both important and difficult.

“For example, if a patient had difficulty reading his or her mail, the therapist would use a magnification device to train and practice with the patient until he or she could successfully read the mail,” says Deemer.

The supportive therapy group acted as a control group for comparison. These patients met with a social worker for six one-hour sessions of talk therapy, which emphasized personal expression about loss and disability. In essence, the researchers say, this group got attention and empathetic support but not specific occupational therapy directed to improve their ability to function.

Four months after treatment, the researchers followed up with the patients in the study. Before treatment, the occupational therapy group’s average PHQ-9 score was 5.5, and the supportive therapy group’s average score was 5.6, placing both groups at the borderline of having a depressive disorder. After re-administering the questionnaire after treatment, the researchers found that the occupational therapy patient group’s average score decreased to 4.62 and the supportive therapy’s score decreased to 4.54.

At this follow-up, the researchers found that 26 percent of the supportive therapy patients reported that their depression symptoms worsened, while only 12 percent of the occupational therapy patients reported worsening symptoms. In total, these data show that while both forms of therapy decreased depression in patients, the group that received occupational therapy reduced its risk of depression by much more.

Comprehensive low vision rehabilitative services typically incorporate specialized care from an optometrist and other rehabilitation therapists, including occupational therapists. Because the VITAL study was not originally designed to distinguish the differences among these particular low-vision rehabilitation services, Deemer says one limitation of her findings is the researchers were unable to measure visual function improvements from occupational therapy services alone. Rather, the effects on visual function seen here are the result of comprehensive low vision rehabilitative care, including services given by both the optometrist and the occupational therapist.

Deemer says the costs associated with occupational therapy are often covered by Medicare, but such services appear to be underutilized.

“Many caregivers and patients may not realize how prevalent depression is among people with low vision, and our duty as health care providers is to raise awareness of the problem and the availability of help,” says Deemer. “It is good practice not only to refer low vision patients to a mental health expert, but to also suggest low vision rehabilitation and occupational therapy, which could have a huge impact on our patients’ lives.”

Researchers Develop Best-Yet Cell Culture System for Age-Related Macular Degeneration

An international team from the University of Alabama at Birmingham and University College London and Queens University Belfast in the United Kingdom developed a cell culture model that could help to develop earlier treatment strategies for age-related macular degeneration, the third most prevalent cause of vision loss worldwide.

In AMD, which is twice as prevalent in older persons as Alzheimer’s disease, the part of the retina used for detailed vision degenerates. Extracellular deposits rich in fats and proteins, called drusen, accumulate under support cells (retinal pigment epithelium) thus blocking transport between the photoreceptors and their blood supply.

Drusen are major early risk factors for both neovascularization and geographic atrophy. These are the late forms of AMD usually with irreversible vision loss, although neovascularization is managed with monthly injections in the eye. It is thought that understanding how drusen are formed is key to stopping these late complications.

Drusen do not occur naturally in laboratory animals, except in primates after several decades of life. Therefore a suitable cell culture model should accelerate the development of early treatment strategies. Previous cell culture models recapitulated several aspects of drusen formation except the formation of hydroxyapatite, a recently discovered key component of drusen growth.

In research published in Investigative Ophthalmology and Visual Science, a team led by Christine Curcio, Ph.D., Matthew Pilgrim, Ph.D., and Imre Lengyel, Ph.D., reported that retinal pigment epithelium cells removed directly from a pig eye can lay down all the major constituents of drusen: lipids, proteins and other trace elements, as well as hydroxyapatite when the cells are grown on specific surfaces. This model confirms the hypothesis that RPE cells in early AMD are functional, and that the conditions of the so-called Bruch’s membrane on which retinal pigment epithelium cells grow in the eye is likely to be essential for drusen formation.

The team expects that a readily reproducible and valid model system will be an important step in determining what molecules in drusen, and what changes in retinal pigment epithelium cells living over drusen, promote advancement to late stages of AMD.

The elderly are the fastest-growing segment of the population, and new drug targets to help older persons maintain the good vision required for independent living are eagerly sought.

In the United States, funding sources included the National Institutes of Health, Department of Energy, International Retinal Research Foundation, EyeSight Foundation of Alabama and Research to Prevent Blindness.

Saving Sight In Glaucoma: Why The Brain May Hold The Key

What causes vision loss in glaucoma? There are two common answers that at first may seem disparate: the first is pressure, as in elevated ocular pressure, and the second is damage to the optic nerve, which is the structure that sends visual information to the brain. Both answers are correct.

Glaucoma involves sensitivity to ocular pressure (not just elevated pressure) that is translated or transduced to stress that degrades the optic nerve over time. Current glaucoma therapies lower pressure using eye drops, surgery, or both in order to reduce stress transduced to the optic nerve. This approach is effective for many patients. But for those who continue to lose vision, where should we turn for new clinical therapies?

One idea is to consider where ocular pressure exerts its influence: the optic nerve head. This structure in the back of the eye defines where nerve fibers leave the retina and enter the optic nerve. The nerve head contains lateral structures that support these fibers but also couple the nerve to the rest of the eye. In this way, pressure in the front of the eye can cause stress to the optic nerve. While we do not understand precisely how this stress is conveyed, we do know that aging of the nerve head is likely to contribute to its susceptibility. By addressing age-related factors, new research might reveal therapies based on reducing the sensitivity of the nerve head to pressure.

What about the optic nerve itself? Like the brain, the optic nerve and retina are part of the central nervous system. Once damaged beyond a certain point, these structures cannot heal. For patients who have lost substantial optic nerve tissue in glaucoma, the hope of regenerative medicine is to restore connectivity with the brain by introducing new nerve fibers or inducing damaged ones to regrow.

Another area of promise that may be forthcoming leverages the idea that increasing brain activity in some cases increases its resistance to stress. Catalyst for a Cure (CFC) research has demonstrated a “window of structural persistence” in which connectivity between the optic nerve and brain remains even when glaucoma affects visual function. During this “window,” optic nerve fibers attempt to boost their electrical activity through natural self-repair mechanisms.

New research by CFC investigators shows that enhanced activity can also help optic nerve fibers regenerate. Perhaps the best approach to a new type of nerve-based glaucoma treatment would combine optic nerve regenerative techniques with those that promote intrinsic repair in the brain.

Simple Procedure Could Improve Treatment for Common Eye Disease

A new, minimally invasive procedure appears to be effective for many patients with Fuchs endothelial dystrophy (FED), a common eye disease, without the potential side effects and cost of the current standard of care, a cornea transplant.

In a proof-of-concept study, published in the journal Cornea, researchers led by Kathryn Colby, MD, PhD, the Louis Block professor and chairman of the Department of Ophthalmology and Visual Science at the University of Chicago, showed that removing a few square millimeters of a single layer of cells on the inside of the cornea allowed rejuvenation of the surrounding tissue, without the need for a corneal transplant. This simple procedure restored clear vision to three out of four patients suffering from FED, the most frequent cause for corneal transplantation in the United States.

Over the past two years while at Harvard Medical School, Colby performed the new procedure, known as Descemet stripping, on 11 patients, aged 51 to 91. Two patients had the procedure in both eyes, one at a time.

When assessed six months after the operation, ten of the treated eyes (77 percent) had clear corneas and eight had 20/20 vision or better (two patients had retinal disease that limited their final vision). The other three eyes did not respond and required a standard cornea transplant.

“It’s too soon to call this a cure,” Colby said. “We performed the first operation just over two years ago. But when it works, it’s a wonderful thing. It’s quick, inexpensive and it spares patients from having someone else’s cells in their eyes, which requires local immunosuppression.”

The first patient to undergo Descemet stripping, 69-year-old Eric Thorp of the Boston area, was pleased. “It’s quite a breakthrough,” he said. His vision, now 20/20 in that eye, “is equivalent to what I had as a boy,” he said. “Amazing.”

“It’s kind of an honor to have been the first,” he added. “It was worth doing.”

Descemet stripping involves removing a small patch of the corneal endothelium (the pumping cells that stop working in FED) attached to an underlying layer (the Descemet membrane). In patients with FED, water accumulates in the cornea, the clear front window of the eye, because of the dysfunction of the pumping cells, causing reduced vision, glare and haloes. If left untreated, the condition progresses to painful blindness.

Removal of the central dysfunctional cells enables healthier peripheral cells to migrate to the center of the cornea, where they reestablish pumping capacity and removal of fluid from the layers above. This gradually restores clear vision.

“Although Descemet stripping is a relatively simple procedure, its potential is revolutionary,” Colby said. In 2015, 14,000 corneal transplants were performed in the United States, just for FED, the most common reason for this operation. The transplants work well, but the tissues are expensive and there is a limited supply in some areas of the world. Because the corneal transplant tissue is foreign, patients must apply topical steroids for the rest of their lives to dampen their immune response and prevent rejection of the transplanted cells. Steroid eye drops are known to cause glaucoma and cataract and can predispose to infection.

The researchers classified patients into four groups based on how they responded to Descemet stripping. Fast responders regained clear vision within a month after surgery. Responders recovered within three months. Slow responders took more than three months. Nonresponders had persistent corneal edema and required endothelial keratoplasty—a streamlined cornea transplant.

Of the 13 eyes treated, four were fast responders, four were responders and two were slow responders.

The next step is to try to understand why some patients, about one out of four, don’t respond to removal of the dysfunctional cells. Fuchs dystrophy is a polygenic disease, but in the last few years researchers have found connections between the extent of a repeating nonsensical genetic abnormality seen in other neurological diseases and the severity of FED. Colby hopes to find genetic clues that predict which patients are most likely to respond to this approach.

Thorp, the first patient treated, had 20/20 vision when last assessed in January of 2016 at the University of Chicago, 24 months after his operation. He was first diagnosed with FED and had a cornea transplant in his right eye in 2002, a two-stage operation. It was successful, but the recovery process meant “foggy vision” in that eye for nearly a year. This prevented him from driving.

That eye slowly recovered, but by 2013 vision in the left eye began to decline. After Colby offered her new procedure and explained the logic behind it, Thorp felt “a great deal of confidence and understanding in what she was doing,” he said. He volunteered to go first.

“It certainly turned out to be worth it,” Thorp said. His operation, removal of a cataract plus Descemet stripping, took less than 30 minutes. That was “about 20 minutes for the cataract and one minute for the stripping,” he recalled.

“After I performed Mr. Thorp’s surgery, I waited eight months to make sure nothing unexpected happened to his cornea,” Colby said, “then I started offering the procedure to patients whom I felt could benefit.”

“Few things remind you as constantly as deteriorating vision,” Thorp recalled. “Your world steadily narrows as you lose the ability to see. But mine expanded again at the other end. I remember walking the dog at night right after the operation. Each night, the streetlights would be a little more in focus. You could see the improvement, night after night over the course of a few weeks, like the fog lifting out of London. It was cool. Really cool.”

Visual Impairment, Blindness Cases in U.S. Expected to Double by 2050

With the youngest of the baby boomers hitting 65 by 2029, the number of people with visual impairment or blindness in the United States is expected to double to more than 8 million by 2050, according to projections based on the most recent census data and from studies funded by the National Eye Institute, part of the National Institutes of Health. Another 16.4 million Americans are expected to have difficulty seeing due to correctable refractive errors such as myopia (nearsightedness) or hyperopia (farsightedness) that can be fixed with glasses, contacts or surgery.

The researchers were led by Rohit Varma, M.D., director of the University of Southern California’s Roski Eye Institute, Los Angeles, and published their analysis May 19th in JAMA Ophthalmology. They estimate that 1 million Americans were legally blind (20/200 vision or worse) in 2015. Having 20/200 vision means that for clear vision, you would have to be 20 feet or closer to an object that a person with normal vision could see from 200 feet away.

Meanwhile, 3.2 million Americans had visual impairment in 2015—meaning they had 20/40 or worse vision with best possible correction. Another 8.2 million had vision problems due to uncorrected refractive error.

“These findings are an important forewarning of the magnitude of vision loss to come. They suggest that there is a huge opportunity for screening efforts to identify people with correctable vision problems and early signs of eye diseases. Early detection and intervention—possibly as simple as prescribing corrective lenses—could go a long way toward preventing a significant proportion of avoidable vision loss,” said NEI Director Paul A. Sieving, M.D., Ph.D.

Over the next 35 years, Varma and his colleagues project that the number of people with legal blindness will increase by 21 percent each decade to 2 million by 2050. Likewise, best-corrected visual impairment will grow by 25 percent each decade, doubling to 6.95 million. The greatest burden of visual impairment and blindness will affect those 80 years or older as advanced age is a key risk factor for diseases such as age-related macular degeneration and cataract.

The researchers analyzed data on visual impairment and blindness from six large studies: the Beaver Dam Eye Study (Beaver Dam, Wisconsin), Baltimore Eye Survey and Salisbury Eye Evaluation Study (Maryland), the Chinese American Eye Study (Monterey Park, California), Los Angeles Latino Eye Study, and Proyecto VER (Nogales and Tucson, Arizona). They used the 2014 census and population growth projections to estimate the nationwide prevalence of vision impairment and blindness now and in 2050.

In terms of absolute numbers, non-Hispanic whites, particularly white women, represent the largest proportion of people affected by visual impairment and blindness, and their numbers will nearly double. By 2050, 2.15 million non-Hispanic white women are expected to be visually impaired and 610,000 will be blind. “Based on these data, there is a need for increased screening and interventions across all population, and especially among non-Hispanic white women,” Varma said.

African Americans currently account for the second highest proportion of visual impairment, but that is expected to shift to Hispanics around 2040, as the Hispanic population—and particularly the number of older Hispanics—continues to grow. Hispanics have particularly high rates of diabetes, which is associated with diabetic eye disease, a treatable cause of visual impairment.

African Americans, meanwhile, are expected to continue to account for the second highest proportion of blindness. “African Americans are at disproportionately high risk for developing glaucoma, a potentially blinding eye disease that typically causes the loss of peripheral, but not central vision, so people tend to not realize that they are losing their vision and do not seek treatment,” he said.

First Skin-to-Eye Stem Cell Transplant in Humans Successful

Researchers have safely transplanted stem cells derived from a patient’s skin to the back of the eye in an effort to restore vision. The research is being presented at the 2016 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) this week in Seattle, Wash.

A small piece of skin from the patient’s arm was collected and modified into induced pluripotent stem cells (iPSC). The iPSCs were then transformed into eye cells, which were transplanted into the patient’s eye. The transplanted cells survived without any adverse events for over a year and resulted in slightly improved vision. The patient suffered from advanced wet age-related macular degeneration (AMD) that did not respond to current standard treatments.

iPSCs are adult cells that have been reprogrammed to an embryonic stem cell-like state, which can then be differentiated into any cell type found in the body.