Category: Ophthalmology

Categories : OphthalmologyTags :

All in the Eyes: High Resolution Retinal Maps Aid Disease Diagnoses

On By ModernMedia
Photoreceptor cells in the retina. Credit: Scientific Animations

Researchers have conducted one of the largest eye studies in the world to reveal new insights into retinal thickness, highlighting its potential in the early detection of diseases like type 2 diabetes, dementia and multiple sclerosis.

The WEHI-led study, using cutting-edge artificial intelligence technology to analyse over 50 000 eyes from the UK Biobank, producing maps of the retina in unprecedented detail to better understand how retinal differences link to various diseases.

The findings, published in Nature Communications, open up new possibilities for using routine eyecare imaging as a tool to screen for and manage diseases, much like mammograms have for breast cancer.

Unlocking a window into the brain

The retina is part of the central nervous system, which also comprises the brain and spinal cord. Many diseases are linked to degeneration or disruption of this critical system, including neurodegenerative conditions such as dementia and metabolic disorders like diabetes.

Globally, neurological conditions alone are one of the leading causes of disability and illness, with over 3 billion people, or 43% of the world’s population living with a brain related condition.

Lead researcher, WEHI’s Dr Vicki Jackson, said the findings broaden the horizons for using retinal imaging as a doorway into the central nervous system, to help manage disease.

“We’ve shown that retinal imaging can act as a window to the brain, by detecting associations with neurological disorders like multiple sclerosis and many other conditions,” said Dr Jackson, a statistician and gene expert.

“Our maps’ fine-scale measurements reveal critical new details about connections between retinal thinning and a range of common conditions.”

The study also identified new genetic factors that influence retinal thickness, which are likely to play a role in the growth and development of a person’s retina.

“This research underscores the potential for retinal thickness to act as a diagnostic biomarker to aid in detecting and tracking the progression of numerous diseases. We can now pinpoint specific locations of the retina which show key changes in some diseases.”

The international research team, led by WEHI, applied AI methods to big population data of retinal imaging and compared information about each person’s genetics and health to reveal unprecedented links to disease.

The results created 50 000 maps with measurements at over 29 000 locations across the retina, identifying retinal thinning relating to 294 genes that play an important role in disease.

AI fast-tracking the diagnostic future

Study lead and bioinformatician, Professor Melanie Bahlo AM, said past studies had indicated correlations between retinal thickness and disease, but her team’s AI-powered discoveries shed deeper light on the complex spatial anatomy of the retina and its role in disease.

“Technologies like AI fuel discovery, and when fused with brilliant minds, there is an extraordinary ability to transform big population data into far-reaching insights,” Prof Bahlo, a lab head at WEHI, said.

“There has never been a time in history where this powerful combination — technology, big data and brilliant minds — has come together to advance human health.”

The research reinforces the growing field of oculomics (using the eye to diagnose health conditions) as an emerging, powerful and non-invasive approach for predicting and diagnosing diseases.

Source: Walter and Eliza Hall Institute

Categories : OphthalmologyTags :

Study Shows Effectiveness of Method to Stem Myopia

On By ModernMedia
Photo by Ksenia Chernaya

Capping ten years of work to stem the tide of myopia, David Berntsen, Professor of Optometry at the University of Houston, is reporting that his team’s method to slow myopia not only works – but lasts.

The original Bifocal Lenses In Nearsighted Kids (BLINK) Study showed that having children with myopia wear high-add power multifocal contact lenses slows its progression. Now, new results from the BLINK2 Study, that continued following these children, found that the benefits continue even after the lenses are no longer used.

“We found that one year after discontinuing treatment with high-add power soft multifocal contact lenses in older teenagers, myopia progression returns to normal with no loss of treatment benefit,” reports Berntsen in JAMA Ophthalmology.

The study was funded by the National Institutes of Health’s National Eye Institute with collaborators from the Ohio State University College of Optometry.

In Focus: A Major Issue

Leading the team at the University of Houston, Berntsen takes on a significant challenge. By 2050 almost 50% of the world (5 billion people) will be myopic. Myopia is associated with an increased risk of long-term eye health problems that affect vision and can even lead to blindness.

From the initial study, high-add multifocal contact lenses were found to be effective at slowing the rate of eye growth, decreasing how myopic children became. Because higher amounts of myopia are associated with vision-threatening eye diseases later in life, like retinal detachment and glaucoma, controlling its progression during childhood potentially offers an additional future benefit.

“There has been concern that the eye might grow faster than normal when myopia control contact lenses are discontinued. Our findings show that when older teenagers stop wearing these myopia control lenses, the eye returns to the age-expected rate of growth,” said Berntsen.

“These follow-on results from the BLINK2 Study show that the treatment benefit with myopia control contact lenses have a durable benefit when they are discontinued at an older age,” said BLINK2 study chair, Jeffrey J. Walline, associate dean for research at the Ohio State University College of Optometry.

Eye Science

Myopia occurs when a child’s developing eyes grow too long from front to back. Instead of focusing images directly on the retina, they are focused at a point in front of the retina.

Single vision prescription glasses and contact lenses can correct myopic vision, but they fail to treat the underlying problem, which is the eye continuing to grow longer than normal. By contrast, soft multifocal contact lenses correct myopic vision in children while simultaneously slowing myopia progression by slowing eye growth.

Designed like a bullseye, multifocal contact lenses focus light in two basic ways. The centre portion of the lens corrects nearsightedness so that distance vision is clear, and it focuses light directly on the retina. The outer portion of the lens adds focusing power to bring the peripheral light into focus in front of the retina. Animal studies show that bringing light to focus in front of the retina may slow growth. The higher the reading power, the further in front of the retina it focuses peripheral light.

BLINK Once…Then Twice

In the original BLINK study, 294 myopic children, ages 7 to 11 years, were randomly assigned to wear single vision contact lenses or multifocal lenses with either high-add power (+2.50 diopters) or medium-add power (+1.50 diopters). They wore the lenses during the day as often as they could comfortably do so for three years. All participants were seen at clinics at the Ohio State University, Columbus, or at the University of Houston.

After three years in the original BLINK study, children in the high-add multifocal contact lens group had shorter eyes compared to the medium-add power and single-vision groups, and they also had the slowest rate of myopia progression and eye growth.

Of the original BLINK participants, 248 continued in BLINK2, during which all participants wore high-add (+2.50 diopters) lenses for two years, followed by single-vision contact lenses for the third year of the study to see if the benefit remained after discontinuing treatment.

At the end of BLINK2, axial eye growth returned to age-expected rates. While there was a small increase in eye growth of 0.03 mm/year across all age groups after discontinuing multifocal lenses, it is important to note that the overall rate of eye growth was no different than the age-expected rate. There was no evidence of faster than normal eye growth.

Participants who had been in the original BLINK high-add multifocal treatment group continued to have shorter eyes and less myopia at the end of BLINK2. Children who were switched to high-add multifocal contact lenses for the first time during BLINK2 did not catch up to those who had worn high-add lenses since the start of the BLINK Study when they were 7 to 11 years of age.

By contrast, studies of other myopia treatments, such as atropine drops and orthokeratology lenses that are designed to temporarily reshape the eye’s outermost corneal layer, showed a rebound effect (faster than age-normal eye growth) after treatment was discontinued.

“Our findings suggest that it’s a reasonable strategy to fit children with multifocal contact lenses for myopia control at a younger age and continue treatment until the late teenage years when myopia progression has slowed,” said Berntsen.

Source: University of Houston

Categories : New Compounds and Treatments OphthalmologyTags :

New Potential Treatment for Inherited Blinding Disease Retinitis Pigmentosa

On By ModernMedia

Researchers used a computer screening approach to identify two compounds that could help prevent vision loss in people with a genetic eye disease

Photoreceptor cells in the retina. Credit: Scientific Animations

Two new compounds may be able to treat retinitis pigmentosa, a group of inherited eye diseases that cause blindness. The compounds, described in a study published January 14th in the open-access journal PLOS Biology by Beata Jastrzebska from Case Western Reserve University, US, and colleagues, were identified using a virtual screening approach.

In retinitis pigmentosa, the retina protein rhodopsin is often misfolded due to genetic mutations, causing retinal cells to die off and leading to progressive blindness. Small molecules to correct rhodopsin folding are urgently needed to treat the estimated 100 000 people in the United States with the disease. Current experimental treatments include retinoid compounds, such as synthetic vitamin A derivatives, which are sensitive to light and can be toxic, leading to several drawbacks.

In the new study, researchers utilised virtual screening to search for new drug-like molecules that bind to and stabilise the structure of rhodopsin to improve its folding and movement through the cell. Two non-retinoid compounds were identified which met these criteria and had the ability to cross the blood-brain and blood-retina barriers. The team tested the compounds in the lab and showed that they improved cell surface expression of rhodopsin in 36 of 123 genetic subtypes of retinitis pigmentosa, including the most common one. Additionally, they protected against retinal degeneration in mice with retinitis pigmentosa.

“Importantly, treatment with either compound improved the overall retina health and function in these mice by prolonging the survival of their photoreceptors,” the authors say. However, they note that additional studies of the compounds or related compounds are needed before testing the treatments in humans.

The authors add, “Inherited mutations in the rhodopsin gene cause retinitis pigmentosa (RP), a progressive and currently untreatable blinding disease. This study identifies small molecule pharmacochaperones that suppress the pathogenic effects of various rhodopsin mutants in vitro and slow photoreceptor cell death in a mouse model of RP, offering a potential new therapeutic approach to prevent vision loss.”

Provided by PLOS

Categories : Mental Health OphthalmologyTags :

Is Paranoia Partly a Visual Problem?

On By ModernMedia
Photo by Stormseeker on Unsplash

Could complex beliefs like paranoia have roots in something as basic as vision? A new Yale study finds evidence that they might. 

When completing a visual perception task, in which participants had to identify whether one moving dot was chasing another moving dot, those with greater tendencies toward paranoid thinking (believing others intend them harm) and teleological thinking (ascribing excessive meaning and purpose to events) performed worse than their counterparts, the study found. Those individuals more often – and confidently – claimed one dot was chasing the other when it wasn’t.

The findings, published in the journal Communications Psychology, suggest that, in the future, testing for illnesses like schizophrenia could be done with a simple eye test.

“We’re really interested in how the mind is organised,” said senior author Philip Corlett, an associate professor of psychiatry at Yale School of Medicine and member of the Wu Tsai Institute. “Chasing or other intentional behaviours are what you might think of as experiences perceived at a very high-level in the brain, that someone might have to reason through and deliberate. In this study, we can see them low down in the brain, in vision, which we think is exciting and interesting – and has implications for how those mechanisms might be relevant for schizophrenia.”

Paranoia and teleological thinking are similar in that they are both misattributions of intention, but paranoia is a negative perception while teleological thinking tends to be positive. Both patterns of thinking are linked to psychosis and schizophrenia.

Hallucinations are associated with psychosis as well and are often about other people, said Corlett, suggesting there may be a social component to these visual misperceptions.

“So we wondered whether there might be something related to social perception – or misperception, what we refer to as social hallucination – that we could measure and that relate to these symptoms of psychosis,” he said.

For the task, participants were shown dots moving on a screen. Sometimes one dot was chasing another; other times there was no chase. Across different trials of the task, participants had to say whether a chase was occurring or not.

Those with higher degrees of paranoia and teleological thinking (as measured through questionnaires) were more likely than others to say with confidence that a chase was happening when one wasn’t. Essentially, they perceived a social interaction that wasn’t occurring.

In additional experiments, the researchers asked participants to identify which dot was doing the chasing and which dot was being chased. In these results, paranoia and teleological thinking began to diverge.

“People with paranoia were particularly bad at detecting which dot was being chased,” said Santiago Castiello, lead author of the study and a postdoctoral researcher in Corlett’s lab. “And people with high teleology were particularly bad at detecting which dot was doing the chasing.”

That these two types of beliefs differed in this way highlights that they are distinct and may have implications for diagnosis or treatment, said the researchers. The connection to vision may also shift thinking around how the brain gives rise to psychotic symptoms.

“Very few people with congenital blindness develop schizophrenia,” said Castiello. “Finding these social hallucinations in vision makes me wonder if schizophrenia is something that develops through errors in how people sample the visual world.”

While there are no immediate therapeutic implications from these findings, deeper understanding of these beliefs could aid in pharmacological treatment development and risk assessment. 

“One thing we’re thinking about now is whether we can find eye tests that predict someone’s risk for psychosis,” said Corlett. “Maybe there is some very quick perceptual task that can identify when someone might need to talk to a clinician.”

Source: Yale University

Categories : OphthalmologyTags :

Why Some Patients Respond Poorly to Wet Macular Degeneration Treatment

On By ModernMedia
Retina showing reticular pseudodrusen. Although they can infrequently appear in individuals with no other apparent pathology, their highest rates of occurrence are in association with age-related macular degeneration (AMD), for which they hold clinical significance by being highly correlated with end-stage disease sub-types, choroidal neovascularisation and geographic atrophy. Credit: National Eye Institute

A new study from researchers at Wilmer Eye Institute, Johns Hopkins Medicine explains not only why some patients with wet age-related macular degeneration (or “wet” AMD) fail to have vision improvement with treatment, but also how an experimental drug could be used with existing wet AMD treatments to save vision.

Wet AMD, one of two kinds of AMD, is a progressive eye condition caused by an overgrowth of blood vessels in the retina. Such blood vessels – caused by an overexpression of a protein known as VEGF that leads to blood vessel growth – then leak fluid or bleed and damage the retina, causing vision loss.

Despite the severe vision loss often experienced by people with wet AMD, less than half of patients treated with monthly eye injections, known as anti-VEGF therapies, show any major vision improvements. Additionally, for those who do benefit with improved vision, most will lose those gains over time.

Now, in the full report published November 4 in the Proceedings of the National Academy of Sciences, the Wilmer-led team of researchers share how such anti-VEGF therapies may actually contribute to lack of vision improvements by triggering the overexpression of a second protein. Known as ANGPTL4, the protein is similar to VEGF, as it can also stimulate overproduction of abnormal blood vessels in the retina.

“We have previously reported that ANGPTL4 was increased in patients who did not respond well to anti-VEGF treatment,” says Akrit Sodhi, MD, PhD, corresponding author and associate professor of ophthalmology at the Johns Hopkins University School of Medicine and the Wilmer Eye Institute. “What we saw in this paper was a paradoxical increase of ANGPTL4 in patients that received anti-VEGF injections – the anti-VEGF therapy itself turned on expression of this protein.”

The team compared VEGF and ANGPTL4 levels in the eye fluid of 52 patients with wet AMD at various stages of anti-VEGF treatment. Prior to anti-VEGF injections, patients with wet AMD had high levels of ANGPTL4 and VEGF proteins. After treatment, their VEGF levels predictably decreased, yet ANGPTL4 levels rose higher, indicating ANGPTL4 remained active following the anti-VEGF injections and the treatments contributed to an increase in ANGPTL4. Such ANGPTL4 activity can lead to blood vessel overgrowth and lack of vision improvement.

The team then investigated ways to bridge the gap between patients with increased ANGPTL4 following anti-VEGF treatments by testing the experimental drug 32-134D in mice with wet AMD. The drug decreases levels of a third protein, HIF-1, known to be involved in wet AMD and diabetic eye disease for its role in switching on VEGF production. Researchers believed the HIF-inhibitor 32-134D would have a similar effect on ANGPTL4 following anti-VEGF treatment, since ANGPTL4 production is also turned on by HIF-1.

In mice treated with 32-134D, the team observed a decrease in HIF-1 levels and VEGF, as well as decreased levels of ANGPTL4 and blood vessel overgrowth. Mice treated only with anti-VEGF therapies corroborated the team’s findings in human patients: levels of VEGF were lower, yet ANGPTL4 levels rose, preventing anti-VEGF therapies from fully working to prevent blood vessel growth (and vision loss). Researchers also determined that combining 32-134D with anti-VEGF treatments prevented the increase in HIF-1, VEGF and ANGPTL4. This treatment combination was more effective than either drug alone, showing promise for treating wet AMD.

“This work exposes a way to improve anti-VEGF therapy for all patients and potentially help a subset of patients with wet AMD who still lose vision over time despite treatment,” Sodhi says. “Our hope is that this [project] will further the three goals we have related to wet AMD: make current therapies as effective as possible, identify new therapies, and prevent people from ever getting wet AMD.”

Source: John Hopkins Medicine

Categories : IT in Healthcare OphthalmologyTags :

AI Eye to Eye with Ophthalmologists in Diagnosing Corneal Infections

On By ModernMedia
Photo by Victor Freitas on Pexels

A Birmingham-led study has found that AI-powered models match ophthalmologists in diagnosing infectious keratitis, offering promise for global eye care improvements.

Infectious keratitis (IK) is a leading cause of corneal blindness worldwide. This new study finds that deep learning models showed similar levels of accuracy in identifying infection.

In a meta-analysis study published in eClinicalMedicine, Dr Darren Ting from the University of Birmingham conducted a review with a global team of researchers analysing 35 studies that utilised Deep Learning (DL) models to diagnose infectious keratitis.

AI models in the study matched the diagnostic accuracy of ophthalmologists, exhibiting a sensitivity of 89.2% and specificity of 93.2%, compared to ophthalmologists’ 82.2% sensitivity and 89.6% specificity.

The models in the study had analysed a combined total of more than 136 000 corneal images, and the authors say that the results further demonstrate the potential use of artificial intelligence in clinical settings.

Dr Darren Ting, Senior author of the study, Birmingham Health Partners (BHP) Fellow and Consultant Ophthalmologist, University of Birmingham said: “Our study shows that AI has the potential to provide fast, reliable diagnoses, which could revolutionise how we manage corneal infections globally. This is particularly promising for regions where access to specialist eye care is limited, and can help to reduce the burden of preventable blindness worldwide.”

The AI models also proved effective at differentiating between healthy eyes, infected corneas, and the various underlying causes of IK, such as bacterial or fungal infections.

While these results highlight the potential of DL in healthcare, the study’s authors emphasised the need for more diverse data and further external validation to increase the reliability of these models for clinical use.

Infectious keratitis, an inflammation of the cornea, affects millions, particularly in low- and middle-income countries where access to specialist eye care is limited. As AI technology continues to grow and play a pivotal role in medicine, it may soon become a key tool in preventing corneal blindness globally.

Source: University of Birmingham

Categories : OphthalmologyTags :

The Search for an Effective Treatment for Glaucoma

On By ModernMedia
Photo by Ksenia Chernaya

Pete Williams at Karolinska Institutet is one of the few researchers in Sweden concentrating on glaucoma. The goal is an effective treatment, something that stops the degenerative process in the nerve cells of the eye. He is the senior author of a new paper in Nature Communications on how deficiency of the enzyme NMNAT2 renders the nerve cells of the eye vulnerable to neurodegeneration and could be a key in the search for a treatment. 

Glaucoma is very common. Eighty million people worldwide have the eye disease. There is no cure, but there are treatments that lower the pressure in the eye and that can slow down the progression of the disease, which otherwise leads to irreversible blindness.

Not always treatable

“Most people who have heard of glaucoma believe that it can be treated with eye drops and surgery. Unfortunately, this is not entirely true. For many of the patients, the treatment lower the eye pressure but doesn’t prevent further vision loss,” says Pete Williams.

Knowledge about glaucoma has taken time to develop because the disease progresses slowly. This means that in the past, it took many years before researchers could see if a particular treatment had any effect. However, in the last decade or so, the availability of instruments that measure changes in the eye much earlier than the patient experiences them has given new impetus to research into the eye disease.

The importance of NAD

In the 1980s, research into neurodegenerative diseases discovered a link with NAD, a co-enzyme, ie a molecule that binds to an enzyme and makes it active.  Pete Williams’ group was the first to show that NAD levels were low in animal models of glaucoma.

“NAD has many important functions in the body. A lack of it is important for neuronal health and survival in many diseases, but we don’t yet know how to use this information to create a better treatment ” says Pete Williams.

When the body makes NAD, it uses an enzyme NMNAT1. However, in neurons, it needs another enzyme: NMNAT2 (which is only found in neurons). 

“In our recent paper in Nature Communications, we show that NMNAT2 is needed to protect neurons in the eye and that gene therapy can be used to increase levels,” says Pete Willams. “

The research team is now moving on to try to develop new substances that target NMNAT2 in nerve cells. 

Source: Karolinksa Institutet

Categories : OphthalmologyTags :

The Colours of the Sunset Reset Circadian Clocks

On By ModernMedia
Photo by Matteo Vistocco on Unsplash

Those mesmerising blue and orange hues in the sky at the start and end of a sunny day might have an essential role in setting humans’ internal clocks. In new research from the University of Washington in Seattle, a novel LED light that emits alternating wavelengths of orange and blue outpaced two other light devices in advancing melatonin levels in a small group of study participants. 

Published in the Journal of Biological Rhythms, the finding appears to establish a new benchmark in humans’ ability to influence their circadian rhythms, and reflects an effective new approach to counteract seasonal affective disorder (SAD). 

A raft of health and mood problems have been attributed to out-of-sync circadian rhythms. Such asynchrony is encouraged by seasonal changes, a lack of exposure to natural light, graveyard-shift jobs and flights across multiple time zones.  

“Our internal clock tells us how our body’s supposed to act during different times of day, but the clock has to be set, and if our brain is not synced to the time of day, then it’s not going to work right,” said Jay Neitz, a coauthor on the paper and a professor of ophthalmology at the UW School of Medicine. 

Circadian rhythms are trained and reset every day by the 24-hour solar cycles of light and dark, which stimulate circuits in the eyes that communicate to the brain. With that information, the brain produces melatonin, a hormone that helps organisms become sleepy in sync with the solar night. 

People who spend many daily hours in artificial light often have circadian rhythms whose melatonin production lags that of people more exposed to natural light. Many commercial lighting products are designed to offset or counteract these lags. 

Most of these products, Neitz said, emphasise blue wavelength because it is known to affect melanopsin, a photopigment in the eyes that communicates with the brain and is most sensitive to blue. 

By contrast, “the light we developed does not involve the melanopsin photopigment,” Neitz explained. “It has alternating blue and orange wavelengths that stimulate a blue-yellow opponent circuit that operates through the cone photoreceptors in the retina. This circuit is much more sensitive than melanopsin, and it is what our brains use to reset our internal clocks.”

The paper’s lead author was James Kuchenbecker, a research assistant professor of ophthalmology at the UW School of Medicine. He sought to compare different artificial lights’ effects on the production of melatonin.  

He and colleagues devised and conducted a test of three devices:

  • a white light of 500 lux (a brightness appropriate for general office spaces)
  • a short-wavelength blue LED designed to trigger melanopsin
  • the newly developed LED of blue and orange wavelengths, which alternate 19 times a second to generate a soft white glow

The goal was to see what lighting approach was most effective at advancing the phase of melatonin production among six study participants. All participants underwent the following regimen with exposure to each of the three test lights:

The first evening, multiple saliva samples were taken to discern the baseline onset and peak of the participants’ melatonin production. For each subject, the onset of this phase dictated when they were exposed to the test light for two hours in the morning. That evening, saliva samples were again taken to see whether subjects’ melatonin phase had started earlier relative to their individual baselines.

During each test, exposure to other light sources was controlled. The three test spans were spaced such that subjects could return to their normal baseline phases before starting a new device.

In terms of shifting the melatonin-production phase, the alternating blue-orange LED device worked best, with a phase advance of 1 hour, 20 minutes. The blue light produced a phase advance of 40 minutes. The white, 500-lux light elicited an advance of just 2.8 minutes. 

Gesturing toward the light that his team developed, Neitz explained. 

“Even though our light looks like white to the naked eye, we think your brain recognizes the alternating blue and orange wavelengths as the colours in the sky. The circuit that produced the biggest shift in melatonin wants to see orange and blue.” 

Source: UW Medicine

Categories : Ophthalmology TransplantsTags :

One Year On, Eye Transplant Yields Insights to Restoring Vision

On By ModernMedia

The world’s first partial face and whole eye transplant has yielded important insights towards the development of functional eye transplants.

Over one year ago, a surgical team at NYU Langone Health transplanted part of a donor face onto a 46-year old power line worker who had suffered extensive facial injuries and the loss of his left eye. They also transplanted a complete eye into the patient, connecting it up to blood vessels and nerves, to see whether it was possible for an eye to survive. Now, findings on the health of the transplanted eye published in JAMA reveal that the eye is healthy but no light has been seen from it.

For the roughly 40 million people around the world without sight in either eye, stem cell research has been the most recent hope for regaining vision in many cases of trauma and disease.

In the eye transplant, the optic nerve was attached and immunosuppression used. Fluorescein angiography showed that perfusion of the globe and retinal were maintained throughout the immediate postoperative period. Optical coherence tomography revealed atrophy of inner retinal layers and attenuation and disruption of the ellipsoid zone.

Crucially, the retina of the transplanted eye responded to light as confirmed by serial electroretinography. MRI scans demonstrated the integrity of the transplanted visual pathways and potential occipital cortical response to light stimulation of the transplanted eye. However, after one year, no light in the eye was observed by the patient.

As discussed in an accompanying editorial published in JAMA Network, whole eye transplantation (WET) has been regarded as one of the most difficult yet important transplant procedures to attempt developing. In 1978, a report from the National Eye Institute advisory stated that “[a]t present, any effort to transplant a mammalian eye is doomed to failure by the ganglion cell axon’s inability to withstand cutting, by the difficulty of insuring adequate circulation of blood to the transplanted eye during or shortly after operation, and lastly by immune rejection of foreign tissue.”

With this transplant case, the issues of adequate circulation and immune rejection have now been shown to be surmountable, the authors point out. Other issues to address concern connecting the cranial nerves to enable opening of the eyelid.

Categories : Genetics OphthalmologyTags :

Gene Therapy for Inherited Blindness Results in 100-fold Vision Improvement

On By ModernMedia
Photo by Victor Freitas on Pexels

People with a rare genetic mutation that causes significant vision loss early in childhood experienced a 100-fold improvement in vision after receiving a corrective gene therapy. Some patients even experienced a 10 000-fold improvement in their vision after receiving the highest dose of the therapy, according to researchers from the Perelman School of Medicine at the University of Pennsylvania who co-led the clinical trial published in The Lancet.

“That 10 000-fold improvement is the same as a patient being able to see their surroundings on a moonlit night outdoors as opposed to requiring bright indoor lighting before treatment,” said the study’s lead author, Artur Cideciyan, PhD, a research professor of Ophthalmology and co-director of the Center for Hereditary Retinal Degenerations. “One patient reported for the first time being able to navigate at midnight outdoors only with the light of a bonfire.”

A total of 15 people participated in the Phase 1/2 trial, including three paediatric patients. Each patient had Leber congenital amaurosis as the result of mutations in the GUCY2D gene, which is essential to producing proteins critical for vision. This specific condition, which affects less than 100 000 people worldwide and is abbreviated as LCA1, causes significant amount of vision loss as early as infancy.

All subjects had severe vision loss with their best measure of vision being equal or worse than 20/80 – meaning if a typically-sighted person could see an object clearly at 80 feet (24m), these patients would have to move up to at least 20 feet (6m) to see it. Glasses provide limited benefit to these patients because they correct abnormalities in the optical focusing ability of the eye, and are unable to address medical causes of vision loss, such as genetic retinal diseases like LCA1.

The trial tested different dosage levels of the gene therapy, ATSN-101, which was adapted from the AAV5 microorganism and was surgically injected under the retina. For the first part of the study, cohorts of three adults each received either a low, mid, ore high dose. Evaluations were held between each level of dosage to ensure that they were safe before upping the dosage for the next cohort. A second phase of the study involved only administering the high dosage levels to both an adult cohort of three and a paediatric cohort of three, again after safety reviews of the previous cohorts.

Improvements were noticed quickly, often within the first month, after the therapy was applied and lasted for at least 12 months. Observations of participating patients are also ongoing. Three of six high-dosage patients who were tested to navigate a mobility course in varying levels of light achieved the maximum-possible score. Other tests used eye charts or measured the dimmest flashes of light patients perceived in a dark environment.

Of the nine patients who received the maximum dosage, two had the 10 000-fold improvement in vision.

“Even though we previously predicted a large vision improvement potential in LCA1, we did not know how receptive patients’ photoreceptors would be to treatment after decades of blindness,” said Cideciyan. “It is very satisfying to see a successful multi-center trial that shows gene therapy can be dramatically efficacious.”

Primarily, the study sought to determine the safety of the gene therapy and its varying dosage levels. Researchers did find some patients had side effects, but the overwhelming majority were related to the surgical procedure itself. The most common side effect was conjunctival haemorrhage, the breakage of small blood vessels underneath the clear surface of the eye, which healed. Two patients had eye inflammation that was reversed with a course of steroids. No serious side effects were related to the study drug.

This work comes on the heels of another successful ophthalmological trial at Penn restoring sight in patients with a different form of LCA. Earlier in 2024, CRISPR-Cas9 gene editing was used to improve the sight of many patients with a form of LCA tied to mutations in the CEP290 gene. Co-led by one of the new paper’s co-authors, Tomas S. Aleman, MD, professor in ophthalmology and co-director with Cideciyan of the Center for Hereditary Retinal Degenerations, the study used similar tests and was the first time children were involved in any gene editing work.

“The treatment success in our most recent clinical trials together with our earlier experience brings hope for a viable treatment for about 20 percent of infantile blindness caused by inherited retinal degenerations,” Aleman said. “The focus now is on perfecting the treatments and treating earlier manifestations of these conditions once safety is confirmed. We hope similar approaches will lead to equally positive outcomes in other forms of congenital retinal blindness.”

Moving forward, approval of this experimental medicine for clinical use requires a randomised controlled trial.

Source: University of Pennsylvania School of Medicine