Category: Ophthalmology

Categories : OphthalmologyTags :

The Colours of the Sunset Reset Circadian Clocks

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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

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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

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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

Categories : OphthalmologyTags :

Air Mercy Service Partners with Metropolitan Health for Eye Care Outreach

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Metropolitan Health, a subsidiary of Momentum Health Solutions, partners with The SA Red Cross Air Mercy Service (AMS) to offer eye-care outreach to communities in need

Johannesburg, South Africa – 26 August 2024 – In South Africa, where a staggering 80% of the population relies on public healthcare1, the issue of eye health often goes unnoticed. With the majority of eye care professionals operating in the private sector, accessible eye care remains a privilege for the remaining 20% of South Africa’s population. A startling revelation from a survey by Statistics South Africa2 shows that only about 9.2% of the population use spectacles as a corrective device. Even more concerning is the fact that visual impairment ranks as the most prevalent disability, affecting 10.3% of the population3.

To address these challenges, Metropolitan Health has proudly partnered with The SA Red Cross Air Mercy Service (AMS) to enhance the vision and quality of life for underserved communities across South Africa. This collaboration will see Momentum’s health business donating funds to provide screening, refractions, and spectacles to recipients during the months of August and September 2024.

Vision care is a critical aspect of overall health and well-being. Poor vision can significantly impact an individual’s quality of life, affecting their ability to work, learn, and engage in daily activities. By providing spectacles to those in need, this partnership aims to improve the vision of many and, in so doing, create opportunities for education and employment.

The AMS is a non-profit aero-medical organisation that provides essential medical services to remote and underserved communities in South Africa. By utilising aviation and other resources, AMS ensures that critical health services are accessible to those in need. Their mission is to bridge the gap in healthcare access by delivering aero-medical services, rescue and health outreach programmes to communities that are often overlooked.

“Partnerships are essential in driving impactful change across South Africa’s communities. This initiative will not only enhance the vision of those in need but also empower them to lead more productive and fulfilling lives. Our approach and commitment to Corporate Social Investment (CSI) projects is to deliver long-term, sustainable impact. By addressing critical health needs, we continue to support initiatives that foster community wellbeing and development,” says Dr Ali Hamdulay, CEO of Metropolitan Health.

Committed to making a real difference in the lives of people by creating access to affordable, quality healthcare services and offerings amidst a challenging and ever-changing operating environment, Momentum Health Solutions and its subsidiary Metropolitan Health believe in the power of impactful CSI initiatives that create lasting change. By partnering with organisations such as AMS, it aims to extend its reach and make a meaningful difference in the lives of individuals and communities.

“The AMS is dedicated to driving meaningful change in remote rural areas through our close collaboration with the KwaZulu-Natal Department of Health. Our partnership with Metropolitan Health is crucial for ensuring our outreach programme has a lasting and sustainable impact on these underserved communities. Addressing eye care needs in rural communities is vital to improving overall health and quality of life. The outreach programme is dedicated to bridging the gap in access to essential healthcare services ensuring that even the most remote areas receive the support they need. By focusing on these underserved populations, we address critical health needs and strengthen our commitment to providing equitable healthcare across our country. We are grateful to Metropolitan Health for this valuable partnership that makes a meaningful contribution towards social impact in South Africa,” says Farhaad Haffejee, AMS CEO.

“This collaboration exemplifies our commitment to improving health outcomes and fostering sustainable development. We look forward to working closely with AMS and other partners to continue addressing critical health needs and creating lasting change. Together, we can build a healthier, more equitable future for all South Africans,” concludes Dr Hamdulay.

Categories : OphthalmologyTags :

Eye Health Services in the Public Sector are Critically Impaired – it is High Time the Health Department Responds

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Photo by Hush Naidoo Jade Photography on Unsplash

By Haseena Majid and Rene Sparks

Despite South Africa producing a substantial number of trained optometrists, the majority of them work in the private sector and in urban areas. This imbalance leaves rural communities underserved and exacerbates health inequities. Does it make sense for us to use public funds and institutions to train people predominantly for the private sector, ask Dr Haseena Majid and Rene Sparks.

Avoidable blindness and vision impairment are major global health concerns. The World Health Organization (WHO) estimates that at least 1 billion people worldwide have a vision impairment that could have been prevented or treated. In 2020, there were an estimated 11 million people living with some degree of vision loss in South Africa, of which 370 000 were classified as blind.

Avoidable blindness caused by uncorrected refractive error (vision problems that requires spectacles or contact lenses) and cataracts can be well managed in the presence of a capable work force that is both accessible and affordable to the public. As such, optometrists are crucial in combating avoidable vision loss. Their expertise in conducting comprehensive eye examinations, diagnosing and managing some eye diseases, prescribing corrective lenses, and providing preventive care is vital for reducing the burden of avoidable blindness.

But the current landscape of optometry services in South Africa reveals significant gaps in both governance and resource allocation.

The distribution of optometrists in South Africa is far from optimal. As of April 2023, there were approximately 4200 registered optometrists and 580 ophthalmologists in the country. While this is a considerable number of people trained to provide primary eye care services, the 6.7% serving the public sector – compared to 93.3% serving the private sector – is simply inadequate and has created stark disparities.

The available evidence points to an urban-rural divide in optometry services, with only around 262 optometrists employed in the public sector nationally, and disproportionately between and within provinces. It means that rural and poor communities, where a significant portion of the population resides, have very limited access to essential eye care services.

Further deepening the disparities in access to essential eye care is the government’s fragmented and inconsistent approach to eye health across provinces, resulting in some areas lacking any public eye care services, while others depend on external providers.

Training misalignment

All of these challenges come against the backdrop of substantial state investment in the training of optometrists. The government funds their training at several universities across the country. However, the majority of these graduates are absorbed into the private sector. In some instances, students trained on state bursaries struggle to get placed in the public sector.

This misalignment highlights a fundamental flaw in how public funds are utilised, with minimal benefit to the broader population that relies on public healthcare. It also contradicts the government’s mandate to provide progressive solutions to improve access to healthcare for all, as enshrined in the Constitution.

These ongoing governance gaps and the inefficient use of state resources also represent significant barriers to achieving health equity in South Africa as expressed in government’s plans for National Health Insurance (NHI). And while the implementation of NHI aims to bring our country closer towards universal health coverage, it is not yet clear whether, and to what extent, vision and eye care services will be included in the envisioned basket of services.

A lack of a clear plan could result in a missed opportunity to integrate optometrists into the primary healthcare system nationally.

What to do

Firstly, there needs to be an urgent reassessment of the costs to train optometrists against the benefits to the broader public. Are we training too many optometrists currently? Could the government initiate engagements with thought leaders and support partners to develop a community service and costing exercise to address the inequity and lack of access to eye health services, and simultaneously address the employment of optometrists within the public health space?

Secondly, the National Department of Health should establish a dedicated directorate for eye health services which should be integrated within provincial health structures. This unit should spearhead a comprehensive data collection system for vision and eye health which can be used to accurately assess needs, allocate resources, and plan effectively.

Calls for such a dedicated directorate have been made through scientific recommendation for more than a decade. But there has been no meaningful response and action from the health department and related decision-making entities.

Thirdly, the principles behind NHI offer a medium-term solution to address the disproportionate distribution of optometrists. Through the establishment of NHI-style public-private partnerships, private sector capacity can be leveraged to serve people who depend on the public sector. Such a public-private partnership will have to have transparency, accountability, and data integrity built into its structures. This will allow provinces and districts to monitor accurate data, and provide feedback that will help shape and improve services.

In summary, the health department stands at a critical juncture, where the systemic imbalances in optometrist distribution and vision care services have now become acute – with people in South Africa paying a very concrete and personal price in the form of avoidable vision loss. Delays in governance processes have historically hampered progress, but the need for swift and informed action is now paramount. The principles of public-private partnership that underlie NHI points to a solution, but the urgency of the crisis means we do not have the time to wait for the full NHI plans to be rolled out – by government’s own admission that will take many years. People losing their eyesight today simply can’t wait that long.

*Majid and Sparks are Global Atlantic fellows for Health Equity in South Africa and advocates on the National Eye Health Advocacy Project led by USAWA for learning and healing, a civil society organisation committed to reforms for health equity and social justice.

Note: Spotlight aims to deepen public understanding of important health issues by publishing a variety of views on its opinion pages. The views expressed in this article are not necessarily shared by the Spotlight editors.

Republished from Spotlight under a Creative Commons licence.

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Categories : New Compounds and Treatments OphthalmologyTags :

Repurposed Drug Combination Promising in the Treatment of Retinal Degenerations

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Retina and nerve cells. Credit: NIH

An international team of researchers have tested a combination treatment incorporating three existing drugs and successfully slowed disease progression in pre-clinical retinopathy models. Their results, which used tamsulosin, metoprolol and bromocriptine are published in Nature Communications.

Drug repurposing refers to the use of existing drugs to treat diseases or conditions which they were not originally developed or approved for, and offer a strategy to treat rare diseases for which new drug development is too costly. The new study focused on drug repurposing in the context of inherited retinal degenerations, IRDs. IRDs are a group of genetic diseases that cause the deterioration of retinal anatomy and function, leading to gradual loss of vision and often blindness. Most IRDs are currently inaccessible therapeutically, comprising an unmet medical need for a substantial population worldwide.

A combination treatment incorporating three drugs slowed disease progression 

The researchers found that a combination treatment incorporating three drugs significantly slowed disease progression and decreased disease manifestation in four different animal models of IRD. The combination included the blood pressure and heart failure drug metoprolol, and tamsulosin, which is used for the treatment of benign prostatic hyperplasia, as well as the nowadays less commonly used Parkinson’s disease drug bromocriptine.

“In drug repurposing, it does not matter to which diseases or conditions the drugs were originally developed for, but it is the molecular-level effects of drugs, or pharmacology, that count,” says first author Dr Henri Leinonen, currently Adjunct Professor of Neuropharmacology at the University of Eastern Finland.

In retinal degenerations, intracellular secondary messengers such as cyclic adenosine monophosphate and calcium are believed to be overactive, exacerbating the disease. Metoprolol, tamsulosin and bromocriptine suppress the activity of these secondary messengers via their own distinct cell membrane-receptor actions.

“We hypothesised that the combined effect of these drugs would alleviate the disease, which it indeed did in several distinct animal models of IRDs. However, the efficacy and safety of this combination in humans with retinal degeneration is not guaranteed, and controlled clinical trials to test these are needed,” Dr Leinonen notes.

It is noteworthy that none of the drugs used in the study were effective against retinal degeneration on their own; instead, their combination was necessary for efficacy. According to Dr Leinonen, the same phenomenon may apply to many diseases that are currently untreatable, and especially in multifactorial diseases, effective treatment may require multiple drugs to be used simultaneously.

Drug repurposing could provide solutions especially for the treatment of rare diseases

Rare diseases, IRDs included, are seldom of major interest for the pharmaceutical industry due to a lack of economic incentives. But drug repurposing, actively researched in academia, is a promising method to find solutions for rare diseases that remain therapeutically inaccessible.

The most significant advantages of drug repurposing can be found in faster drug development times and lower costs. Since repurposed drugs have already undergone several mandatory safety tests and early stages of clinical trials, their market entry is considerably faster and cheaper than that of completely new drugs. Drug safety is also an important aspect, as the relative safety of repurposed drugs compared to a completely new chemical reduces risks and uncertainty, which is often considered the most critical point in the drug development process.

Source: University of Finland

Categories : Diet and Nutrition OphthalmologyTags :

In New Study, Supplements Slow Late-stage Age-related Macular Degeneration

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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

In a new analysis of data, researchers at the National Institutes of Health (NIH) have found that taking a daily supplement containing antioxidant vitamins and minerals slows progression of late-stage dry age-related macular degeneration (AMD), potentially helping people with late-stage disease preserve their central vision.

Age-related macular degeneration affects the macula, the part of the retina that provides central vision.

Researchers reviewed the original retinal scans of participants in the Age-Related Eye Diseases Studies (AREDS and AREDS2) and found that, for people with late-stage dry AMD, taking the antioxidant supplement slowed expansion of geographic atrophy regions towards the central foveal region of the retina. The study was published in the journal Ophthalmology.

“We’ve known for a long time that AREDS2 supplements help slow the progression from intermediate to late AMD. Our analysis shows that taking AREDS2 supplements can also slow disease progression in people with late dry AMD,” said Tiarnan Keenan, MD, PhD, of NIH’s National Eye Institute (NEI) and lead author of the study. “These findings support the continued use of AREDS2 supplements by people with late dry AMD.”

In their new analysis, the researchers reviewed the original retinal scans of participants in the AREDS (total 318 participants, 392 eyes) and AREDS2 (total 891 participants, 1210 eyes) trials who developed dry AMD, calculating the position and expansion rate of their regions of geographic atrophy. For those people who developed geographic atrophy in their central vision, the supplements had little benefit. But for the majority who developed geographic atrophy far from the fovea, the supplements slowed the rate of expansion towards the fovea by approximately 55% over an average of three years.

In early and intermediate AMD, the light-sensing retina at the back of the eye develops small yellow deposits of fatty proteins called drusen. When the disease progresses to the late stage, people can develop leaky blood vessels (“wet” AMD) or can lose regions of light-sensitive cells in the retina (“dry” AMD). The geographic atrophy in these regions slowly expands over time, causing people to progressively lose their central vision.

The original AREDS trial found that a supplement formula containing antioxidants (vitamin C, E, and beta-carotene), along with zinc and copper, could slow progression of intermediate to late-stage AMD. The subsequent AREDS2 trial found that substituting the antioxidants lutein and zeaxanthin for beta-carotene improved the efficacy of the supplement formula and eliminated certain risks. At the time, neither trial detected any further benefit once participants had developed late-stage disease.

However, that original analysis did not account for a phenomenon in the dry form of late AMD called “foveal sparing.”  While all regions of the retina are sensitive to light, the region that gives us the highest acuity central vision is called the fovea. Many people with dry AMD first develop geographic atrophy outside this foveal region, and they only lose their central vision when the geographic atrophy regions expand into the foveal area.

“Our high acuity central vision is essential for tasks like reading and driving. Given that there are few therapeutic options for people with late-stage dry AMD to retain or restore their vision, antioxidant supplementation is a simple step that may slow central vision loss, even for those with late disease,” Keenan said. “We plan to confirm these findings in a dedicated clinical trial in the near future.”

Learn more about AREDS and AREDS2

Source: NIH/National Eye Institute

Categories : OphthalmologyTags :

Reduced Retinal Cell Oxygen Use in Glaucoma Tied to Faster Vision Loss

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Retina and nerve cells. Credit: NIH

Glaucoma occurs when retinal ganglion cells start to die, and the main risk factors are high eye pressure and older age. Currently, all licensed treatments are designed to lower pressure in the eye – also known as intraocular pressure. However, some patients still continue to lose their sight following treatment.

Retinal cells are particularly energy hungry. To help doctors better understand who will lose their vision faster, the new study, published in Nature Medicine, asked whether mitochondrial function, measured in white blood cells, is lower in people with glaucoma than those without glaucoma and if mitochondrial function is associated with the rate at which glaucoma patients lose vision.

The researchers assessed 139 participants who were already receiving treatment to lower intraocular pressure and 50 healthy people acting as a control (comparison) group.

They measured how well cells in the blood use oxygen, how much vision was lost over time and nicotinamide adenine dinucleotide (NAD) levels. NAD is a molecule in the body that helps cells produce energy and is made from vitamin B3 in the diet.

Firstly, the researchers discovered that certain cells in the blood, known as peripheral blood mononuclear cells, use oxygen differently in people with glaucoma. The team measured how much oxygen these cells use and found that people whose blood cells used less oxygen tended to lose their vision faster, even if they were being treated to lower intraocular pressure. This measurement explained 13% of the differences in how fast patients lost vision.

Additionally, people with glaucoma were found to have lower levels of NAD in their blood cells compared to people without glaucoma. These lower NAD levels were linked to the lower oxygen use in the blood cells.

Senior author, Professor David (Ted) Garway-Heath (UCL Institute of Ophthalmology and Moorfields Eye Hospital), said: “White blood cell mitochondrial function and NAD levels, if introduced as a clinical test, would enable clinicians to predict which patients are at higher risk of continued vision loss, allowing them to be prioritised for more intensive monitoring and treatment.

“If further research shows that low mitochondrial function or low NAD levels are a cause for glaucoma, then this opens the way for new treatments.

“UCL and Moorfields Eye Hospital are currently leading a major clinical trial funded by the Medical Research Council and the National Institute for Health and Care Research, to establish whether high-dose vitamin B3 can boost mitochondrial function and reduce vision loss in glaucoma.*

“We hope that this will open a new avenue for treatment of glaucoma patients which does not depend on lowering the eye pressure.”

Source: University College London

Categories : Metabolic Disorders OphthalmologyTags :

Study Reveals Association Between Semaglutide Use and Optic Neuropathy

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Photoreceptor cells in the retina. Credit: Scientific Animations

Researchers from Mass Eye and Ear have discovered an association between semaglutide use and an increased risk of nonarteritic anterior ischaemic optic neuropathy (NAION) in patients with type 2 diabetes, overweight or obesity. The findings, which appear in JAMA Ophthalmology, only show an association and cannot establish causation.

Though NAION is relatively rare, occurring in in about 10 in 100 000, it is the second most common cause of optic nerve blindness, behind glaucoma, and it is the most common cause of sudden optic nerve blindness. Caused by decreased blood flow to the optic disc, it usually affects only one eye but in 15% of cases both eyes are involved. There are no treatments for this disease and little prospect for improvement, although it is painless.

The study was led by Joseph Rizzo, MD, director of the Neuro-Ophthalmology Service at Mass Eye and Ear and the Simmons Lessell Professor of Ophthalmology at Harvard Medical School.

In mid-2023 Rizzo, a resident (study co-author Seyedeh Maryam Zekavat, MD, PhD) and other Mass Eye and Ear neuro-ophthalmologists noticed a disturbing trend – three patients in their practice had been diagnosed with vision loss from this relatively uncommon optic nerve disease in just one week. They did notice however that all three were taking semaglutide.

“The use of these drugs has exploded throughout industrialised countries and they have provided very significant benefits in many ways, but future discussions between a patient and their physician should include NAION as a potential risk,” said Rizzo, corresponding author of the study. “It is important to appreciate, however, that the increased risk relates to a disorder that is relatively uncommon.” 

This prompted the Mass Eye and Ear research team to run a retrospective analysis of their patient population to see if they could identify a link between this disease and these drugs.

They performed matched cohort study of 16 827 patients revealed higher risk of NAION in patients prescribed semaglutide compared with patients prescribed non–GLP-1 receptor agonist medications for diabetes or obesity.

The researchers found that patients with diabetes who were prescribed and took semaglutide were four times (hazard ratio [HR], 4.28) more likely to be receive a NAION diagnosis. The odds increased to more than seven times (HR, 7.64) when the prescription was for weight control in obesity.

The researchers analysed the records of more than 17 000 Mass Eye and Ear patients treated over the six years since Ozempic was released and divided the patients in those who were diagnosed with either diabetes or overweight/ obesity. The researchers compared patients who had received prescriptions for semaglutide compared to those taking other diabetes or weight loss drugs. Then, they analysed the rate of NAION diagnoses in the groups, which revealed the significant risk increases.

Study limitations include the fact that Mass Eye and Ear sees an unusually high number of people with rare eye diseases, and the number of NAION cases seen over the six-year study period is relatively small. With small case numbers, statistics can change quickly, Rizzo noted. Medication adherence could also not be assessed.

Only correlation can be shown by the study, not causality. How or why this association exists remains unknown. Likewise, the reason for the reported difference between diabetic and overweight groups – but this does not appear to result from a difference in baseline characteristics. The optic nerve is known to host GLP-1 receptors, but the study did not adequately address all the confounding factors. They also caution against generalising the results (from a majority white population) since Black individuals have a lower risk of NAION.

“Our findings should be viewed as being significant but tentative, as future studies are needed to examine these questions in a much larger and more diverse population,” Rizzo said. “This is information we did not have before and it should be included in discussions between patients and their doctors, especially if patients have other known optic nerve problems like glaucoma or if there is pre-existing significant visual loss from other causes.”

Categories : Genetics OphthalmologyTags :

CRISPR Treatment Improves Vision in Inherited Retinal Degeneration

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Photo by Jeffrey Riley on Unsplash

About 79% of clinical trial participants experienced measurable improvement after receiving experimental, CRISPR-based gene editing that is designed to fix a rare form of blindness, according to a paper published in the New England Journal of Medicine.

“This trial shows CRISPR gene editing has exciting potential to treat inherited retinal degeneration,” said corresponding author Mark Pennesi, MD, PhD. “There is nothing more rewarding to a physician than hearing a patient describe how their vision has improved after a treatment. One of our trial participants has shared several examples, including being able to find their phone after misplacing it and knowing that their coffee machine is working by seeing its small lights.

Pennesi is an ophthalmologist and Oregon Health & Science University’s lead scientist for the Phase 1/2 BRILLIANCE trial, which evaluated the safety and effectiveness of EDIT-101, an experimental CRISPR-based gene editing treatment developed by Editas Medicine. The experimental treatment was designed to edit a mutation in the CEP290 gene, which provides instructions to create a protein that is critical for sight.

People with this gene mutation have a rare condition that is commonly called Leber Congenital Amaurosis, or LCA, Type 10, for which there is currently no Food and Drug Administration-approved treatment. LCA’s various types occur in about 2 or 3 out of 100 000 newborns.

The OHSU Casey Eye Institute treated the trial’s first participant in early 2020. That procedure also marked the first time that CRISPR had been used to edit genes within the human body, called in vivo gene editing.

The new paper describes the study’s findings through February 2023 and details how the trial’s 14 participants – 12 adults and two children – responded to receiving EDIT-101 in one eye. Key results include:

  • 11 participants, about 79%, showed improvement in at least one of four measured outcomes.
  • 6 participants, about 43%, showed improvement in two or more outcomes.
  • 6 participants, about 43%, reported improved vision-related quality of life.
  • 4 participants, about 29%, had clinically meaningful improvement in visual acuity, or how well they could identify objects or letters on a chart.
  • There were no serious adverse events related to the treatment.
  • Most adverse events were mild or moderate, and all have since been resolved.

Four specific outcomes were used to evaluate the experimental treatment’s effectiveness:

  • Visual acuity
  • How well participants did in a full-field test, which involves seeing coloured points of light while looking into a specialised device
  • How well participants navigated a research maze with physical objects and varying amounts of light
  • How much participants reported experiencing improved quality of life

Further research for a future treatment

In November 2022, trial sponsor Editas Medicine announced that it was pausing the trial’s enrolment and would seek another partner to continue the experimental therapy’s development. Pennesi and colleagues are exploring working with other commercial partners to conduct additional trials, in collaboration with Editas. The researchers hope future studies can examine ideal dosing, whether a treatment effect is more pronounced in certain age groups such as younger patients, and include refined endpoints to measure impacts on activities of daily living.

Source: Oregon Health & Science University