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Biomed Bites, Neuroscience, Ophthalmology, Research, Stanford News, Technology

The retina: One researcher’s window into the brain

The retina: One researcher's window into the brain

Welcome to Biomed Bites, a weekly feature that introduces readers to some of Stanford’s most innovative researchers. 

Initially, Stephen Baccus, PhD, wanted to understand how computers work. It didn’t take him very long to discover that the snazziest computer around is the human brain. Now an associate professor of neurobiology, Baccus needed a simple way to study neural circuits. He picked the retina, a component that is relatively well understood.

As Baccus explains in the video above:

In choosing the retina, I wanted to choose a set of experiments we could do where we could control the brain very accurately in order to study it, and I found that the retina was one of the places that we could most accurately control what the input to the nervous system is doing.

It’s a simple enough part of the brain that we can really hope to understand how it works.

Although Baccus and his team are interested in the general principles of neural function that can be observed using the retina, they’re also eager to discover clinical applications of their research such as electronic retinal prostheses.

“From our basic studies on how the retina performs computations, this information can be and actually has been used in the design of prostheses that we believe can actually restore sight,” Baccus says.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: New retinal implant could restore sight, All data — big and small — informs large-scale neuroscience project and Stanford expert responds to questions about brain repair and the future of neuroscience

Ophthalmology, Pediatrics, Research, Stanford News

Eye injuries in children from non-powder guns on the rise, new study says

Eye injuries in children from non-powder guns on the rise, new study says

paintball-2Eye injuries from BB guns, pellet guns and other non-powder firearms have become more common in recent years in U.S. kids, according to a paper published this month by the Journal of the American Association for Pediatric Ophthalmology and Strabismus. 

The study, led by Stanford ophthalmologist Douglas Fredrick, MD, looked at eye injuries from recreational activities that were severe enough to send children to emergency departments between 2002 and 2012. (Fredrick has seen his share of pediatric eye injuries in his work treating kids at Lucile Packard Children’s Hospital Stanford.)

Non-powder guns caused more eye injuries than all other causes put together, including fireworks and such sports as baseball, tennis and hockey. Many of the injuries caused permanent damage to children’s eyesight, though the proportion of kids who had their vision damaged depended on the type of gun that injured them.

The paper found that since 2006, eye injuries from paintball guns, a type of non-powder gun, have dropped off. Face masks worn for paintball are very effective at preventing eye injuries, as the photo above illustrates.

But this good news was offset by increased eye injuries from air guns, which include BB guns, pellet guns and “airsoft” guns that fire lightweight plastic bullets. From a press release issued by the journal:

“These results demonstrate that air guns can cause severe, yet preventable, eye injury among the pediatric population,” explained [Fredrick]. “To reduce rates of pediatric eye injury, both practitioners and air gun companies should promote and lobby for eye safety mandates among all air gun users. Furthermore, changes in state policy to regulate possession and usage of air guns among minors may be warranted to reduce rates of accidental injury.”

Previously: Instagram for eyes: Stanford ophthalmologists develop low-cost device to ease image sharing, Study: ER statistics could be used to reduce gun violence and New retinal implant could restore sight
Photo by Victoria Padevit Brown

Applied Biotechnology, Bioengineering, Ophthalmology, Research, Science, Technology

New retinal implant could restore sight

New retinal implant could restore sight

2618400441_c19946dff4_zIf your car battery runs out of juice, the car won’t run, but that doesn’t mean it’s time to scrap the car. Similarly (at least slightly), if your photoreceptors are worn out due to a disease such as retinitis pigmentosa or macular degeneration, then you might not be able to see, but your eyes still have a lot of functioning parts.

That’s the principle behind a new retinal implant developed by team of Stanford-led researchers. Unlike previous devices, which require wires and unwieldy surgeries, the new implant is wireless and needs only a minimally invasive surgery to inject a small, photovoltaic chip inside the eye. The team published their results in Nature Medicine.

That chip capitalizes on the remaining capabilities of existing retinal cells known as bipolar and ganglion cells and produces more refined images than existing devices. The chip responds to signals from special glasses worn by the recipient.

“The performance we’re observing at the moment is very encouraging,” Georges Goetz, a lead author of the paper and graduate student in electrical engineering at Stanford, said in our press release. “Based on our current results, we hope that human recipients of this implant will be able to recognize objects and move about.”

The implant has only been used in animal studies, but a clinical trial is planned next year in France.

“Eventually, we hope this technology will restore vision of 20/120,” co-senior author Daniel Palanker, PhD, told me. “And if it works that well, it will become relevant to patients with age-related macular degeneration.”

Previously: Stanford researchers develop solar powered wireless retinal implant, Factors driving prescription decisions for macular degeneration complex — and costly and Tiny size, big impact: Ultrasound powers miniature medical implant 
Photo by Ali T

Aging, Health Costs, Medicine and Society, Ophthalmology, Research, Stanford News

Factors driving prescription decisions for macular degeneration complex – and costly

Factors driving prescription decisions for macular degeneration complex - and costly

5197694152_fbbfe73c21_zFor the last decade or so of her life, my grandma was basically blind. Her eyes, like those of many seniors, suffered from macular degeneration, a progressive disorder that affects the macula, a small spot near center of the retina critical for clear vision.

She lived her last years in a nursing home in Iowa and I honestly don’t know what drugs, if any, she took for this condition, much less how much they cost.

But multiplied by millions (macular degeneration is the most common cause of visual impairment in older adults), the costs are a big deal. That’s why Stanford researchers set out to understand why doctors would prescribe one drug, ranibizumab (let’s call it r) at a cost of $2,000 a dose over bevacizumab (b), which runs $50 a dose.

They published their findings in Health Affairs today.

Both drugs are equally effective and have similarly severe side effects. And, according to a 2011 report, if all Medicare doctors had prescribed b rather than r in 2011, the system would have saved $1.1 billion.

Stanford researchers hypothesized that Medicare physicians — who face a financial incentive to prescribe more expensive drugs — would be more inclined to prescribe r than Veterans Affairs physicians, who don’t have the same incentive.

Instead, as health economist Kate Bundorf, PhD, told me, it’s much more complex.

Continue Reading »

Applied Biotechnology, Bioengineering, Ophthalmology, Stanford News, Videos

A medical invention that brings tears to your eyes

A medical invention that brings tears to your eyes

dry-eye-implantMore than 20 million Americans suffer from dry eye, a painful condition where a personal’s lacrimal glands don’t create enough tears to lubricate the surface of the eye.

But relief is around the corner for these sufferers – a tiny implantable device that stimulates natural tear production on a long-term basis is currently in clinical trials. The device increases tear volume by delivering micro-electrical pulses to the lacrimal gland. It’s inserted into the mucus lining of the sinus cavity or under the skin beneath the eyebrow. Tear delivery rates can be adjusted manually with a wireless controller. (You can watch a video of this device producing tears, below.)

This clever invention is the brainchild of bioengineer and former Stanford Biodesign fellow Michael Ackermann, PhD, who says he spent a good part of his boyhood in Louisville, Kentucky, taking apart things like VCRs, radios and weed-whackers.

“My parents wanted me to be a doctor, but it was very clear from a young age that I was going to be an engineer,” said Ackermann.

He’s now at the helm of Oculeve, a 20-person startup dedicated to helping people with dry-eye. Ackermann’s tale of how he took one crazy idea and turned it into a product that has the potential to help millions of people is featured in the latest issue of Inside Stanford Medicine.

More than one person’s story, it’s another example of the efficacy of the Stanford Biodesign training program, whose fellows have started 36 medtech companies and filed more than 200 patents, all of which have reached 250,000-plus patients.

Previously: Crying without tears unlocks the mystery of a new genetic disease, Instagram for eyes: Stanford ophthalmologists develop low-cost device to ease image sharing and Stanford-developed eye implant could work with smartphone to improve glaucoma treatments
Photo and video by Michael Ackermann

Aging, Imaging, Ophthalmology, Patient Care, Research, Stanford News

New way to predict advance of age-related macular degeneration

New way to predict advance of age-related macular degeneration

eyeballAge-related macular degeneration, in which the macula – the key area of the retina responsible for vision – begins to degenerate, is the leading cause of blindness and central vision loss among adults older than 65. Some 10-15 million Americans suffer from the disease.

If those numbers don’t scare you, try these: “It affects 14%-24% of the U.S. population aged 65-74 years and 35 -40% of people aged 74 years or more have the disease.” Yow!

Most cases of AMD don’t lead to blindness. But if the disorder progresses to an advanced stage where abnormal blood vessels accumulate underneath the macula and leak blood and fluid, irreversible damage to the macula can quickly ensue if treatment doesn’t arrive right on time.

Timing that treatment just right is a real issue. As I wrote in my recent release about a promising development in this field:

[U]ntil now, there has been no effective way to tell which individuals with AMD are likely to progress to the wet stage. Current treatments are costly and invasive – they typically involve injections of medicines directly into the eyeball – making the notion of treating people with early or intermediate stages of AMD a non-starter. Doctors and patients have to hope the next office visit will be early enough to catch wet AMD at its onset, before it takes too great a toll.

Here’s the good news: A team led by Stanford radiologist and biomedical informatician Daniel Rubin, MD, has found a new way to forecast which patients with age-related macular degeneration are likely to progress to the most debilitating form of the disease – and when.

The advance, chronicled in a study in Investigative Ophthalmology & Visual Science, is a formula – derived from extensive computer analysis of thousands of retinal scans of hundreds of patients’ eyes – that recommends, on a personalized basis,  when to schedule an individual patient’s next office visit in order to optimize the prospect of catching AMD progression before it causes blindness.

The formula predicts, with high accuracy, whether and when a patient with mild or intermediate AMD will progress to the dangerous advanced stage. And it does so simply by crunching imaging data that is already commonly collected in eye doctors’ offices anyway.

“Our technique involves no new procedures in the doctor’s office – patients get the same care they’ve been getting anyway,” Rubin told me. His team just tacked on a sophisticated, computerized image-processing step.

Previously: Treating common forms of blindness using tissue generated with ink-jet printing technology, To maintain good eyesight, make healthy vision a priority and Stanford researchers develop web-based tool to streamline interpretation of medical images
Image courtesy of Daniel Rubin

Applied Biotechnology, Ophthalmology, Public Health, Stanford News, Technology

Stanford-developed eye implant could work with smartphone to improve glaucoma treatments

Stanford-developed eye implant could work with smartphone to improve glaucoma treatments

eyeGlaucoma, caused by rising fluid pressure in the eyes, is known as the silent thief of sight. Catching the disease in the early stages is critical because if detected too late it leads to blindness. Regular monitoring and controlling of the disease once detected is invaluable.

Now, Stephen Quake, PhD, professor of bioengineering at Stanford, and Yossi Mandel, MD, PhD, an applied physics and ophthalmologist at Bar-Ilan University in Israel, have developed a tiny eye implant that would allow patients to take daily or hourly measurements of eye pressure from home.

A recent Stanford Report article explains how the device works:

It consists of a small tube – one end is open to the fluids that fill the eye; the other end is capped with a small bulb filled with gas. As the [internal optic pressure] increases, intraocular fluid is pushed into the tube; the gas pushes back against this flow.

As IOP fluctuates, the meniscus – the barrier between the fluid and the gas – moves back and forth in the tube. Patients could use a custom smartphone app or a wearable technology, such as Google Glass, to snap a photo of the instrument at any time, providing a critical wealth of data that could steer treatment. For instance, in one previous study, researchers found that 24-hour IOP monitoring resulted in a change in treatment in up to 80 percent of patients.

“For me, the charm of this is the simplicity of the device. Glaucoma is a substantial issue in human health. It’s critical to catch things before they go off the rails, because once you go off, you can go blind. If patients could monitor themselves frequently, you might see an improvement in treatments,” Quake added.

The full report (subscription required) is published in the current issue of Nature Medicine.

Jen Baxter is a freelance writer and photographer. After spending eight years working for Kaiser Permanente Health plan she took a self-imposed sabbatical to travel around South East Asia and become a blogger. She enjoys writing about nutrition, meditation, and mental health, and finding personal stories that inspire people to take responsibility for their own well-being. Her website and blog can be found at www.jenbaxter.com.

Previously: What I did this summer: Stanford medical student investigates early detection methods for glaucomaTo maintain good eyesight, make healthy vision a priority and Instagram for eyes: Stanford ophthalmologists develop low-cost device to ease image sharing
Photo by Magmiretoby

Behavioral Science, Evolution, Medicine and Society, Ophthalmology, Research

Looks of fear and disgust help us to see threats, study shows

Looks of fear and disgust help us to see threats, study shows

disgustedNext time someone throws you a look, don’t take it personally: In a study of fear and disgust (the facial expressions), researchers have shown how those reactions to threat have helped us survive. Scientists studied the effects of eyes widening in fear, admitting more light and broading a participant’s field of vision, or narrowing in disgust, focusing more precisely on an object. As two-dozen undergraduate volunteers mimicked each emotion, scientists tracked their vision using using standard eye-exam equipment.

From a recent Los Angeles Times article:

Although some scientists have proposed that emotional expressions are intended primarily to communicate information, study authors argued that expressions of fear and disgust seem to perform different visual functions.

“Eye widening may improve detection and localization of a potential threat that requires enhanced vigilance, which would be consistent with the hypothesized function of fear,” wrote senior author Adam Anderson, [PhD,] a professor of human development at Cornell University. (The research was conducted by Anderson and his colleagues at the University of Toronto.)

“Conversely, eye narrowing may improve perceptual discrimination to discern different kinds of threats, such as disease vectors and contaminated foods, avoidance of which is a hypothesized function of disgust,” Anderson and his colleagues wrote.

The study was published in the journal Psychological Science.

Previously: Botox: frozen face = chilled emotional response? and Compassion, Darwin, facial expressions, the Dalai Lama – and counterterrorism?
Photo by Rachael Towne

Genetics, Ophthalmology, Pediatrics, Research, Stanford News

Crying without tears unlocks the mystery of a new genetic disease

Crying without tears unlocks the mystery of a new genetic disease

LittlePackardGirlSometimes one tiny clue holds the key to a baffling medical mystery. That was the case for a San Francisco Bay Area child whose family and doctors struggled for the first three years of her life to pinpoint the cause of her developmental delays and neurologic, muscle, eye and liver problems. The essential clue? Grace Wilsey doesn’t make tears when she cries.

Grace’s combination of symptoms didn’t fit any known condition. Her team of caregivers at Lucile Packard Children’s Hospital Stanford, led by pediatric geneticist Gregory Enns, MB, ChB, strongly suspected that she had an as-yet-undiscovered genetic disease. Several genetics experts at Stanford helped sequence her genome, then came up with a list of eight mutated genes that might be responsible for her symptoms. They ranked the genes in order of likelihood that each was involved and began working down the list to try to pinpoint the culprit.

At the bottom of the list was a gene called NGLY1, which normally codes for N-glycanase 1, a housekeeping enzyme that helps cells break down and recycle mis-folded proteins. Part way through the investigation of the list of eight suspect genes, Grace’s parents, Matt and Kristen Wilsey, contacted a team at Baylor College of Medicine that had also previously performed whole genome sequencing on Grace and consulted on Grace’s case. A postdoctoral associate there, Matthew Bainbridge, PhD, reran Grace’s raw sequence data against the latest algorithms. NGLY1 jumped to the top of the candidate list of what was causing Grace’s underlying condition. As a next step, Dr. Bainbridge searched the scientific literature and found something so new that the Stanford researchers hadn’t yet run across it: a report of one child with suspected NGLY1 deficiency. From our press release about the discovery:

Bainbridge read in the medical literature of another child, studied at Duke University, whose caregivers there suspected his unusual symptoms were tied to an NGLY1 gene defect. But without a second patient for comparison, they weren’t sure.

As part of his detective work, Bainbridge emailed Kristen Wilsey to ask if Grace produced tears when she cried. Wilsey replied that although Grace’s eyes were moist, she never really made tears. Bainbridge wrote back, “I think I have it.”

“My heart jumped out of my chest,” Wilsey said. The first patient identified with NGLY1 deficiency, it turned out, also did not make tears, and the same characteristic has since been observed in seven of the eight children with NGLY1 gene defects whom the researchers have identified.

The scientific implications of the diagnosis are profound: Researchers can start looking for treatments or a cure. So far, the way that malfunctioning N-glycanase 1 causes the children’s symptoms is not understood, so unraveling the connection is a large area of focus for scientists.

They can also look for variants of the disease, Enns told me. “We are likely detecting the most severe form of NGLY1 deficiency – ascertainment bias – and it is quite possible that more mild forms of the disease exist,” he said. The first eight children found with NGLY1 deficiency are described in a new scientific paper publishing today in Genetics in Medicine; Enns and Bainbridge are both primary authors. Of the children, six have the same mutation in their NGLY1 gene and (probably not coincidentally) also share a very severe manifestation of the disease. Two children, including Grace, have different NGLY1 mutations and also have less severe disease, a finding that hints that other children with as-yet-unexplained developmental delays may also have less-severe variants of NGLY1 deficiency.

Continue Reading »

Imaging, Ophthalmology, Research, Stanford News, Technology

Instagram for eyes: Stanford ophthalmologists develop low-cost device to ease image sharing

Instagram for eyes: Stanford ophthalmologists develop low-cost device to ease image sharing

eye-phoneThis probably won’t grab as many headlines as the news of a smartphone that wakes you up with the sizzle and smell of bacon, but it should!

A team of Stanford scientists is using 3D printing to create inexpensive adapters that make it easy to use a smartphone and an ordinary examination lens to capture high-quality images of the front and back of the eye. And – what seems to me as just as important – providing a nearly effortless way to share those images.

“Think Instagram for the eyes,” said one of the developers, assistant professor of ophthalmology Robert Chang, MD.

This is a big deal because most primary-care doctors have no good way to see into patients’ eyes, and no easy way to share the images. The usual eye-imaging instruments are expensive and hard to use, and even ophthalmologists who have the equipment and know-how find capturing and sharing the images slow going.

As one of Chang’s fellow developers, Stanford ophthalmology resident Dave Myung, MD, PhD, told me when I interviewed him for an article in Inside Stanford Medicine:

“A picture is truly worth a thousand words… Imagine a car accident victim arriving in the emergency department with an eye injury resulting in a hyphema – blood inside the front of her eye. Normally the physician would have to describe this finding in her electronic record with words alone. Smartphones today not only have the camera resolution to supplement those words with a high-resolution photo, but also the data-transfer capability to upload that photo securely to the medical record in a matter of seconds.”

The scientists describe the adapters, currently dubbed the EyeGo, in two articles in the new issue (volume 3, issue 1) of Journal of Mobile Technology in Medicine. And you can read my story to learn more about the development process, including how Myung pieced together the first prototype (with plastic bits he ordered from the Internet and a few Legos), how mechanical engineering graduate student Alex Jais created the first printed model on his own 3D printer, and how residents Lisa He, MD, and Brian Toy, MD, are leading studies to test them out.

Those interested in using an EyeGo adapter for research or beta-testing can e-mail the team at eyegotech@gmail.com.

Previously: Image of the Week: Sigmoid volvulus and Treating common forms of blindness using tissue generated with ink-jet printing technology
Photograph by Dave Myung

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