Vision loss in type 2 diabetes results from diabetic retinopathy, caused by damage to blood vessels in the retina, the light-sensitive layer of tissue in the back of your eye. The disease can appear without warning.

“The ability to predict which patients are most at risk could constitute a significant advance in diagnosis and management of diabetes, which has reached epidemic proportions,” said Harrison.  “Early diagnosis and detection, especially if location-specific, could aid in delaying diabetic retinopathy and over the long term, saving sight.”

Diabetes is the number one cause of vision loss in working-age Americans. Also alarming, about 44% of American adults have prediabetes and it is not currently known when and how prediabetes affects the eye. Many patients with prediabetes are unaware of their condition.

Although patients with prediabetes are known to have impaired fasting glucose, impaired glucose tolerance, and elevated hemoglobin A1c, there is still a significant gap in understanding how and when prediabetes impacts eye health.

“It is important that we close this gap as there are no treatments in the eye outside of glycemic control for early type 2 diabetes or prediabetes, and to learn which type of glucose processing changes are most related to eye disease,” said Harrison.

Harrison’s team is undertaking unique research, never done before, in that they will study both the front and the back of the eye and different types of glucose dysfunction. The team includes the laboratories of Rachel Redfern, Maria Walker and Kaitlyn Sapoznik in Optometry and Marc Hamilton in Health and Human Performance. Ted Zderic, Julia Benoit, Deborah Hamilton and Bismark Owusu-Afriyie also have key roles in the project.

To explore how glucose dysregulation affects the vascular and neural retina, cornea, and tear film, the team will investigate whether tests like fat distribution, activity levels, and oral glucose tolerance in type 2 diabetes patients are linked to or can predict ocular health.

“Our central hypothesis is that local retinal oxygenation is altered by changes in glucose tolerance. This drives the relationship between vessel changes and retinal function, in local retinal areas,” said Harrison.

After comparing the subjects, the team will follow up with them after one-and two- years to assess ocular and metabolic changes over time.

“We expect that differences in impaired glucose tolerance and phenotypes will alter ocular testing over time, especially in prediabetes,” said Harrison.

Notably, the study found people with diabetes who had been prescribed semaglutide by their physician and then filled the prescription were more than four times more likely to be diagnosed with NAION. Those who were overweight or had obesity and prescribed this drug were more than seven times more likely to get the diagnosis.

The study, which 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,  published July 3^rd in JAMA Ophthalmology.

“The use of these drugs has exploded throughout industrialized 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, the study’s corresponding author. “It is important to appreciate, however, that the increased risk relates to a disorder that is relatively uncommon.”

NAION is relatively rare, occurring up to 10 out of 100,000 people in the general population. NAION is the second-leading cause of optic nerve blindness (second only to glaucoma) and it is the most common cause of sudden optic nerve blindness. NAION is thought to be caused by reduced blood flow to the optic nerve head, with the consequence of permanent visual loss in one eye. According to Rizzo, the visual loss caused by NAION is painless and may progresses over many days before stabilizing, and there is relatively little potential for improvement. There are currently no effective treatments for NAION.

The impetus for the study occurred in the late summer of 2023 when 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. The physicians observed all three were taking semaglutide.

This anecdotal recognition led the Mass Eye and Ear research team to run a backward-looking analysis of their patient population to see if they could identify a link between this disease and these drugs, which had been surging in popularity.

Semaglutide was developed to treat type 2 diabetes. The drug encourages weight loss, and its use has snowballed since its launch as Ozempic for diabetes in 2017. The drug was also approved for weight management, branded as Wegovy, and released in 2021.

The researchers analyzed 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 analyzed the rate of NAION diagnoses in the groups, which revealed the significant risk increases.

There are several limitations to the study. Mass Eye and Ear sees an unusually high number of people with rare eye diseases, the study population is majority white, 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. The researchers also couldn’t determine if the patients actually took their medication or if they started and then stopped taking semaglutide at some point and how this might have impacted their risk.

Importantly, the study does not prove causality, and the researchers don’t know why or how this association exists, and why there was a difference reported in diabetic and overweight groups.

“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 preexisting significant visual loss from other causes.”

Authorship: In addition to Rizzo and Zekavat, other Mass General Brigham co-authors include Jimena Tatiana Hathaway, MD, MPH (MEE); Madhura P. Shah, BS (MEE); David B. Hathaway, MD (BWH); Drenushe Krasniqi, BA (MEE); John W. Gittinger Jr, MD (MEE); Dean Cestari, MD (MEE); Robert Mallery, MD (MEE); Bardia Abbasi, MD (MEE); Marc Bouffard, MD (MEE); Bart K. Chwalisz, MD (MEE) and Tais Estrela, MD (MEE).

Disclosures: No conflicts of interest reported.

Funding: This work was funded in part by a grant from Research to Prevent Blindness.

Paper cited: Hathaway, J et al. “Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide” JAMA Ophthalmology DOI: 10.1001/jamaophthalmol.2024.2296

About three million people in the U.S. have glaucoma, a group of diseases that damage the optic nerve and lead to vision loss, according to the Centers for Disease Control and Prevention. Doctors use flinch-inducing “air puff tests” during eye exams to take one-time measurements of eye pressure. A slight elevation in pressure, an otherwise imperceptible symptom caused by fluid buildup around the cornea, can lead to a glaucoma diagnosis. Researchers have been testing ways to continuously and more comfortably detect these tiny fluctuations in pressure, such as contact lenses that transmit signals to receptor glasses. However, changing temperatures — like stepping outside into cold weather — can throw off the lenses’ measurements. So, Dengbao Xiao and coworkers wanted to develop a contact lens that accurately measures and wirelessly transmits real-time signals about eye pressure across a wide range of temperatures.

First, Xiao and the team designed two miniature spiral circuits, each with a unique natural vibration pattern that would change when stretched by minute amounts, such as with changes to an eye’s pressure and diameter. To create pressure-detecting contact lenses, the researchers sandwiched these tiny circuits between layers of polydimethylsiloxane, a typical contact lens material. Then they wirelessly read the embedded circuits’ vibration patterns by holding a coil near the lens that was connected to a computer. The transmitted signals were unaffected by tests meant to mimic eye movement, extended exposure to moisture (to simulate damp conditions in the eye), and daily wear and tear.

In laboratory tests, the researchers placed the new lenses on three individual pig eye specimens while controlling the ocular pressures and temperatures. The contact lenses monitored and wirelessly transmitted pressure data from 50 to 122 degrees F. When pressures were calculated from the signal of only one circuit in the lens, the results deviated up to 87% from the true values. However, when information from both circuits was used, the pressure readings differed by only 7% from the true value because the combination removed temperature-related errors. The researchers say that their dual-circuit “smart” lens design has potential to be used for accurate early detection and monitoring of glaucoma, even in a wide range of temperatures.

The authors acknowledge funding from the National Natural Science Foundation of China.

IMAGE: THIS “SMART” CONTACT LENS COULD SOMEDAY HELP MEASURE EYE PRESSURE AND SEND WIRELESS SIGNALS TO ENABLE EARLY DETECTION OF GLAUCOMA.

view more CREDIT: ADAPTED FROM ACS APPLIED MATERIALS & INTERFACES 2024, DOI: 10.1021/ACSAMI.4C02289

Researchers published their results in Big Data Mining and Analytics on April 22.

DED can affect a wide array of people, including those who wear contact lenses, makeup, stay up late, look at screens for a long time and are over 30 years old. Symptoms of this disease are dry eyes, irritation and burning, tears, eye fatigue and pain. One can easily see how this disease has the potential to drastically impact a large portion of the modern world’s population. Here is where the combined efforts of ophthalmic disease detection and the world of computer scientists and engineers can help.

“By addressing challenges, imparting insights, and delineating future research pathways, it contributes substantially to the advancement of ophthalmic disease detection through sophisticated technological modalities,” said Mini Han Wang, author and researcher.

There are seven facets to this AI-based disease detection. Timely intervention via the AI screening process and correct prognosis is the first part. The use of exhaustive surveys for DED through AI is another, and this is a supporting principle to ensure a level of thoroughness and trustworthiness throughout the process. A systematic approach follows, as well as the marriage of computer science and engineering with ophthalmology. Then, the standards for DED detection must be devised and upheld for future researchers and practitioners, which will naturally lead to the advancement of the field. Finally, all the research, methodologies and tools must be compiled so researchers, scholars and practitioners can have all of the information currently out there available to them.

While the ophthalmologists set the guidelines regarding the framework of the disease and flags for diagnosis, the AI does a lot of the heavy lifting. Ideally, this AI would use images and videos taken from a user’s cell phone to help reach users across the world. The AI can then utilize these images, as well as risk factors in the patient’s life, to make a smart and well-informed prognosis. Further, AI continuously learns and can help propel research forward by contributing to predictive models for DED.

The use of AI detection for DED holds a lot of promise, especially considering the risk factors are often normal activities in many people’s everyday lives. To make the detection methods accessible enough and accurate enough, further research needs to be done.

“However, there are still challenges for engineers to select the diagnostic standards and combinations of different types of datasets. By using trustworthy algorithms, images and videos captured from phones for accessibility purposes, a holistic approach to healthcare for early screening is possible,” said Wang.

With continued testing and collaboration between engineers and ophthalmologists, there is great potential for this method of testing to be useful in contributing to early screening of DED and subsequent therapeutic actions taken for the patient to reduce a worsening condition or to recover some quality of life.

Mini Han Wang and Xiangrong Yu of the Zhuhai People’s Hospital with Mini Han Wang also of the Department of Ophthalmology and Visual Sciences at the Chinese University of Hong Kong, The Faculty of Data Sciences at City University of Macau and the Department of big data at the Zhuhai Institute of Advanced Technology at the Chinese Academy of Sciences, Lumin Xing of the First Affiliated Hospital of Shandong First Medical University, Yi Pan of the Shenzhen Institute of Advanced Technology Chinese Academy of Sciences, Feng Gu of the College of Staten Island at the City University of New York, Junbin Fang at the Department of Optoelectronic Engineering at Jinan University, Chi Pui Pang, Kelvin KL Chong, Carol Yim-Lui Cheung and Xulin Liao of the Department of Ophthalmology and Visual Sciences at The Chinese University of Hong Kong, Xiaoxiao Fang with the Zhuhai Aier Eye Hospital, Jie Yang of the College of Artificial Intelligence at Chongqing Industry and Trade Polytechnic, Ruoyu Zhou and Wenjian Liu with the Faculty of Data Science at City University of Macao, Xiaoshu Zhou with the Centre for Science and Technology Exchange and Cooperation between China and Portuguese-Speaking Countries, and Fengling Wang with the School of Artificial Intelligence at Hezhou Univeristy contributed to this research.

The National Natural Science Foundation of China Natural, the Shenzhen Key Laboratory of Intelligent Bioinformatics, the Shenzhen Science and Technology Program, the Guangdong Basic and Applied Basic Research Foundation, the Zhuhai Technology and Research Foundation, the Project of Humanities and Social Science of MOE, the Science and Technology Research Program of Chongqing Municipal Education Commission and the Natural Science Foundation of Chongqing China made this research possible.

Microbial keratitis is one of the most serious potential complications for contact lens wearers. It’s an infection of the cornea that is caused by bacteria; the most common being Pseudomonas aeruginosa.

Previous studies have found that existing disinfecting solutions are not effective for preventing biofilm, which are clusters of bacteria that attach to the surface of lenses.

Hydroquinine, an organic compound found in the bark of some trees, is known to have bacterial killing activity against Pseudomonas aeruginosa and several other clinically important germs, including Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae.

The team behind the discovery, from the University of Portsmouth in England and Naresuan and Pibulsongkram Rajabhat universities in Thailand, has now explored the potential use of multipurpose formulas containing hydroquinine as a disinfectant for contact lenses.

They examined the antibacterial, anti-adhesion, and anti-biofilm properties of hydroquinine-formulated multi-purpose solutions (MPSs), and then compared it to two commercial MPSs; Opti-free Replenish and Q-eye. The natural compound killed 99.9 per cent of bacteria at the time of disinfection.

The paper, published in Antibiotics, says these findings may aid in the development of novel disinfectants aimed at combating the P. aeruginosa bacteria.

Dr Robert Baldock from the School of Pharmacy and Biomedical Sciences at the University of Portsmouth, said: “Commercially available disinfecting solutions, which are made up of a number of chemicals, can sometimes cause reactions with painful side-effects.

“We hoped to demonstrate that new agents made from natural products may be an excellent option to limit or reduce the risk of contact lens contamination.

“It is exciting to see how this research has progressed; from discovery to exploring potential applications.”

There are up to 3.5 million reports of corneal infections annually, and in extreme cases it can result in permanent eye damage and vision loss. The risk of microbial keratitis doubles when someone wears contact lenses overnight and or longer than the recommended daily amount.

Corneal blindness resulting from microbial keratitis is emerging as a prominent cause of visual disability, according to the World Health Organisation (WHO). The World Health Organisation (WHO) has also classified multidrug-resistant P. aeruginosa as one of the most concerning pathogens.

Drug-resistant bacteria occur in more than 2.8 million infections and are responsible for 35,000 deaths per year. Antimicrobial resistance happens when germs change over time and no longer respond to medicines, making it difficult to treat infections.

Amoxicillin and Trimethoprim are commonly prescribed antibiotics that certain strains of P. aeruginosa have become resistant to.

Hydroquinine is already known to be an effective agent against malaria in humans, and it is also being used in the Netherlands to treat nocturnal muscle cramps. Until now, there has been little investigation into its drug-resistant properties.

Lead author, Sattaporn Weawsiangsang from the Faculty Of Allied Health Sciences at Naresuan University, is currently a visiting researcher at the University of Portsmouth.

She said: “Our initial findings suggest that soaking contact lenses in a multi-purpose solution containing hydroquinine is possibly helpful to prevent contamination and infection.

“However, further investigation is needed to determine whether hydroquinine itself also has  adverse reactions or toxicity.

“We are continuing to test the compound on a number of cells, and so far, the results are really promising. This potential development could contribute to the creation of new disinfectants from natural products, effectively combating P. aeruginosa infections and reducing cases of corneal infections.”

The paper concludes by recommending further research examining the effectiveness of hydroquinine with several different contact lens materials, and against other pathogenic microorganisms.

The study, published in The Lancet Regional Health Europe, covers 178 extremely preterm babies at the neonatal units of the university hospitals in Gothenburg, Lund, and Stockholm between 2016 and 2019. Extremely preterm babies are those born before the 28th week of pregnancy.

Around half of the children were given preventive oral nutritional supplements containing the omega-6 fatty acid AA (arachidonic acid) and the omega-3 fatty acid DHA (docosahexaenoic acid). Neither AA nor DHA are included in the supplements that are currently routinely given to extremely preterm babies immediately after birth.

The researchers have previously found that the combination supplement led to the risk of contracting the sight-threatening eye disease ROP (retinopathy of prematurity) being halved. The current study looks at children’s visual development at two and a half years of corrected age (i.e. age from the estimated date of birth).

Pia Lundgren, an associate professor in paediatric eye research at the University of Gothenburg’s Sahlgrenska Academy and a chief physician at Sahlgrenska University Hospital, said the study shows that children who have received the combination supplement had improved visual function, regardless of whether they had previously had ROP.

‘The improved visual development was thus not only due to the beneficial effect on the retina. The supplement also seems to have improved the brain’s ability to interpret visual impressions,’ she said.

The issue of nutrition and supplementation for extremely preterm babies is highly topical within neonatal care in many parts of the world. Sweden currently lacks precise guidelines for administering fatty acid supplements to extremely preterm children, but the guidelines are now being revised – partly based on the current findings.

‘Importantly, we can now demonstrate the positive effects that the combination supplement appears to have on visual development when the child is older,’ Prof Lundgren added. ‘In the continued studies – on the same group of children – we will also look more closely at cognitive and neurological development, which will be particularly interesting.’

Retinal vein occlusion (RVO), an eye disease that affects up to 2% of people over age 40, occurs when a vein in the eye’s retina becomes blocked, leading to swelling in the eye, inflammation, damage to the retina, and vision loss.

Standard therapy involves injecting into the eye a vascular endothelial growth factor inhibitor (anti-VEGF) that reduces swelling. The therapy can improve vision but patients with significant retinal damage due to impaired blood flow often have poor outcomes.

“Anti-VEGF therapy has helped a lot of people with RVO, but the fear factor—having to get a needle in the eye—causes many people to delay treatment, which can lead to retinal damage,” says Carol M. Troy, MD, PhD, professor of pathology & cell biology and of neurology at Columbia University Vagelos College of Physicians and Surgeons. “There’s an opportunity to help more people with this disease that is a leading cause of blindness worldwide.”

The study found that an experimental eye drop treatment was twice as effective as the standard injection therapy at reducing swelling and improving blood flow within the retina of mice with RVO. The eye drops also prevented neurons (photoreceptors) in the retina from deteriorating and preserved visual function over time, whereas the standard injections had no effect on either.

Eye drops target ‘death enzyme’

The eye drops contain an experimental drug that blocks caspase-9, an enzyme that triggers cell death, and was found by Troy’s lab to be overactive in blood vessels injured by RVO.

“We think the eye drops improve the health of blood vessels in the retina, which then decreases the toxic signaling that damages the retina’s neurons and leads to vision loss,” says Maria I. Avrutsky, PhD, the study’s first author who conducted the research as a postdoc in the Troy lab.

Future studies are aimed at preparing to test the eye drops in human clinical trials and identifying additional therapeutic targets.

“Finding the root cause of RVO is the holy grail, but if we can at least provide better symptomatic relief that doesn’t distress patients, it would be a really good start,” Troy says.

More information

The study, “Caspase-9 inhibition confers stronger neuronal and vascular protection compared to VEGF neutralization in a mouse model of retinal vein occlusion,” was published online in Frontiers of Neuroscience.

All authors: Maria I. Avrutsky (Columbia, now at Character Biosciences), Claire W. Chen (Columbia), Jacqueline M. Lawson (Columbia), Scott J. Snipas (Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA) Guy S. Salvesen (Sanford Burnham Prebys), and Carol M. Troy (Columbia).

The study was supported by a sponsored research agreement with Opera Therapeutics and grants from the National Institutes of Health (R01NS091333 and T32EY013933) and the Department of Defense Army/Air Force.

Carol Troy and Maria Avrutsky are inventors on patent applications filed by Columbia University related to the therapeutic use of caspase-9 inhibitors. Maria Avrutsky received consulting income from Opera Therapeutics.

The other authors report no financial or other conflicts of interest.

Dry eye, a common condition in which tears produced by the eye can’t keep the eye adequately lubricated, afflicts approximately 1 in 20 people in the United States. It can cause eye stinging and burning, inflammation, blurry vision and light sensitivity. Extreme cases can result in damage to the eye’s surface if left untreated. The most common treatments involve the application of eye drops, gels or ointment. This new, unconventional treatment involves bacteria in the intestinal tract.

Presenting author Laura Schaefer, Ph.D., of Baylor College of Medicine in Houston, Texas, said, “The ‘friendly’ bacteria that live in the human gastrointestinal tract have been linked to health and protection against disease in many parts of the body, including the gut, brain and lung. It’s therefore not surprising that the gut microbiome also has effects on our eyes.”

Previous work by this research group showed that mice given gut bacteria from human Sjögren syndrome patients with severe dry eye developed worse eye disease under dry conditions than mice that were given gut bacteria from healthy human patients. This suggests that the gut bacteria from healthy people help to protect the surface of the eye in dry conditions. One possible treatment avenue for dry eye would involve probiotic bacteria that have similar protective effects. The group investigated this by using an orally administered probiotic bacterial strain, Limosilactobacillus reuteri DSM17938, in a dry eye mouse model. DSM17938 is a human-derived, commercially available probiotic bacterial strain that has already demonstrated protective effects in the gut and immune system in humans and mice, but it has not been tested in the context of eye health.

Mice were first treated with antibiotics, which kills many of the “friendly” bacteria living in the gut. They were then exposed to very dry conditions and fed daily doses of either probiotic bacteria or a saline solution as a control. After 5 days, the eyes were examined for disease. The mice that were fed the probiotic bacteria had healthier and more intact corneal surfaces. In addition, these mice had more goblet cells in their eye tissue, which are specialized cells that produce mucin, an essential component in tears. Taken together these data suggest that the right oral probiotic could help treat and manage dry eye symptoms.

The authors in this study are Laura Schaefer, Robert Britton, Steven Pflugfelder and Cintia de Paiva. The research was performed in the laboratory of Dr. Cintia de Paiva in the Department of Ophthalmology at Baylor College of Medicine and supported with funds from the National Institutes of Health and the Research to Prevent Blindness Foundation.

“Prior to this study, we didn’t know the best treatment for persistent or recurrent macular edema, a major cause of vision loss in people with uveitis,” said Douglas A. Jabs, M.D., Johns Hopkins Bloomberg School of Public Health, Baltimore, chair of the study. “This trial strongly indicates that repeat intraocular corticosteroid injections are superior to either intravitreal injections of methotrexate or ranibizumab.”

Uveitis is a collection of inflammatory conditions that affect the internal tissues of the eye. Uveitis can affect the front of the eye (anterior uveitis), the middle of the eye (intermediate uveitis), the back of the eye (posterior uveitis), or the front, middle, and back of the eye (panuveitis). Inflammation in the eye can lead to fluid buildup in the central part of the eye’s light-sensing retina, known as the macula, and decrease vision. This fluid buildup, called macular edema, is a complication of uveitis that often persists or recurs over time, despite uveitis treatment.

Initial treatment for uveitis-related macular edema seeks to control inflammation and reduce the fluid under the retina. While some patients achieve this goal with oral corticosteroids, most patients with macular edema also need intraocular corticosteroid injections. The dexamethasone intraocular implant is one such treatment. However, intraocular corticosteroids can raise pressure inside the eye. High intraocular pressure is a key risk factor for glaucoma, which can damage the optic nerve and lead to vision loss. Intraocular corticosteroids can also lead to cataract, a clouding of the eye’s lens, which decreases vision.

In this study, researchers compared three treatments for uveitis-related macular edema: an additional intraocular corticosteroid injection, an injection of the anti-vascular endothelial growth factor (anti-VEGF) drug ranibizumab, or an injection of the anti-inflammatory drug methotrexate. Anti-VEGF injections are used to treat age-related macular degeneration, as well as macular edema due to other causes, such as diabetic retinopathy. Earlier, small pilot studies suggested that ranibizumab injections and the anti-inflammatory effects of methotrexate might help reduce uveitis-related macular edema.

The clinical trial enrolled 194 participants (225 study eyes) with well-controlled uveitis but persistent or recurrent macular edema. Sixty-five participants received a dexamethasone corticosteroid, 65 participants received methotrexate, and 64 participants received ranibizumab. The study took place at 33 clinical centers, located across the United States, the United Kingdom, Australia, and India. All participants had previously received at least one intravitreal corticosteroid injection for uveitis-related macular edema.

The injection schedules for each group were based on how each treatment is generally used in clinical practice. The corticosteroid group participants received one dexamethasone implant injection at baseline and, if the macular edema had not resolved, another injection at eight weeks. The methotrexate group received one injection at baseline, then repeat injections at four and eight weeks if macular edema did not resolve. The ranibizumab group received injections at baseline, four weeks, and eight weeks, even if their macular edema resolved.

After 12 weeks, all three groups showed reductions in retinal swelling. Reduction was greatest in the dexamethasone group compared to the other two (35% reduction for corticosteroid; 20% for ranibizumab; 11% for methotrexate). In addition, only the corticosteroid group showed improvement in vision, nearly five letters—about one row on an eye chart. The corticosteroid group did have more occurrences of mild increases in intraocular pressure, but rises to high levels were infrequent (<10%) in all three groups.

“Intraocular corticosteroid treatment remains the most effective therapy for uveitis-related macular edema,” said Nisha Acharya, M.D., University of California San Francisco, the lead author of the study. “The vision gains in participants who received the corticosteroid treatment were very promising.”

This study was funded by NEI. Allergan and Genentech provided a portion of the dexamethasone implants and ranibizumab, respectively. Clinical Trial number NCT02623426.

Reference: The Multicenter Uveitis Steroid Treatment Trial (MUST) Research Group. “Intravitreal therapy for uveitic macular edema – ranibizumab vs methotrexate vs the dexamethasone implant: The MERIT Trial Results.” Ophthalmology, June 13, 2023.

IMAGE: OPTICAL COHERENCE TOMOGRAPHY (OCT) IMAGE SHOWING MACULAR EDEMA. view more 

CREDIT: IMAGE COURTESY OF NISHA ACHARYA, M.D., UNIVERSITY OF CALIFORNIA SAN FRANCISCO.

The three-year study found that a daily drop in each eye of a low dose of atropine, a drug used to dilate pupils, was better than a placebo at limiting eyeglass prescription changes and inhibiting elongation of the eye in nearsighted children aged 6 to 10.

That elongation leads to myopia, or nearsightedness, which starts in young kids and continues to get worse into the teen years before leveling off in most people. In addition to requiring life-long vision correction, nearsightedness increases the risk for retinal detachment, macular degeneration, cataracts and glaucoma later in life – and most corrective lenses don’t do anything to stop myopia progression.

“The idea of keeping eyeballs smaller isn’t just so people’s glasses are thinner – it would also be so that in their 70s they don’t suffer visual impairment,” said lead study author Karla Zadnik, professor and dean of the College of Optometry at The Ohio State University.

“This is exciting work for the myopia research community, which I’ve been part of for 35 years. We’ve talked about treatment and control for decades,” she said. “And it’s exciting to think that there could be options in the future for millions of children we know are going to be myopic.”

The results of the CHAMP (Childhood Atropine for Myopia Progression) trial are published today (June 1, 2023) in JAMA Ophthalmology.

About one in three adults worldwide is nearsighted, and the global prevalence of myopia is predicted to increase to 50% by 2050. Though one federally approved contact lens can slow progression of nearsightedness, no pharmaceutical products are approved in the United States or Europe to treat myopia.

Animal studies years ago hinted at atropine’s ability to slow the growth of the eye, but the full-strength drug’s interference with near vision and concerns about pupil dilation hindered early considerations of its potential as a human therapy for myopia. More recent research has suggested a low dose of atropine might be the ticket.

This new double-masked, randomized phase 3 trial assessed the safety and effectiveness of two low-dose solutions, with atropine concentrations of either .01% or .02%, versus placebo. Treatment for each of the 489 children aged 6 to 10 assessed for the drug’s effectiveness consisted of one daily drop per eye at bedtime, which minimized the disruption of any blurring effects atropine might have on vision.

Researchers were a bit surprised to find that the most significant improvements at all time points compared to placebo resulted from the solution containing .01% of atropine. Though the .02% atropine formulation was also better at slowing progression of myopia than placebo, the results were less consistent.

“The .01% story is clearer and more obvious in terms of significantly slowing both the growth of the eye as well as then resulting in a lower glasses prescription,” Zadnik said.

Including a measure of the eye’s growth was a key component of the study because “the field is actually moving toward axial elongation being as important as, or more important than, the glasses prescription in terms of the most meaningful outcome,” she said. “If we’re trying to slow eye growth to prevent bad outcomes for people in their 80s, measuring the eye growth directly is really important.”

The drugs’ safety was assessed in a larger sample of 573 participants that also included children as young as 3 and up to age 16. Both low-dose formulations were safe and well tolerated. The most common side effects were sensitivity to light, allergic conjunctivitis, eye irritation, dilated pupils and blurred vision, although reports of these side effects were few.

The CHAMP trial was the first study of low-dose atropine to include placebo controls for three years and to involve a large, diverse population recruited from 26 clinical sites in North America and five countries in Europe. In a second section of the trial, researchers are evaluating how the eyes respond when the treatment is over.

The experimental drug is made without preservatives and, if federally approved as a therapy, would be distributed in single-use packaging for convenience and to prevent contamination. Off-label low-dose atropine that can currently be obtained at compounding pharmacies may contain preservatives that can lead to dry eye and corneal irritation, researchers noted.

The experimental product studied in the CHAMP trial is manufactured by Vyluma, a New Jersey development-stage biopharmaceutical company with a focus on pharmaceutical treatments for refractive errors of the eye. A subsidiary of Nevakar Inc., Vyluma sponsored the trial, has submitted a New Drug Application to the FDA to seek approval in the U.S. and has partnered with two companies to commercialize the product outside the United States..

Zadnik led the study as a paid expert consultant to Vyluma. Jennifer Fogt, assistant professor at Ohio State, also worked on the trial. Additional co-authors Erica Schulman of SUNY College of Optometry; Ian Flitcroft of the Center for Eye Research in Dublin, Ireland; Louis Blumenfeld of Eye Physicians of Central Florida; and Tung Fong, Eric Lang, Houman Hemmati and Simon Chandler of Vyluma represented the CHAMP trial group investigators.

The study, titled, “Stress resilience-enhancing drugs preserve tissue structure and function in degenerating retina via phosphodiesterase inhibition,” was published in the Proceedings of the National Academy of Sciences.

“In this study, we introduce a new class of therapeutics called ‘Stress Resilience-Enhancing Drugs’ (SREDs) for the treatment of neurodegenerative conditions, specifically the world’s leading causes of blindness in age-related and inherited retinal diseases,” said Krzysztof Palczewski, PhD, Donald Bren Professor of Ophthalmology at the UCI School of Medicine and corresponding author on the study. “Through selective, pharmacological inhibition of cyclic nucleotide phosphodiesterases, our prototypical SREDs slowed or halted the development and progression of retinopathies in a number of genetic and environmental animal models.”

Today, approximately 350 million people worldwide suffer from debilitating vision loss caused by either AMD or DR, and a large majority of these cases (>90%) have only minimally effective or no treatment options available. These chronic, progressive retinal diseases, including retinitis pigmentosa, arise from genetic and environmental disruptions of cellular and tissue stability. Such disruptions accumulate with repeated exposures to stress over time, leading to progressive visual impairment and, in many cases, legal blindness. Despite decades of research, therapeutic options for the millions of patients suffering from these disorders remain severely limited, especially for treating earlier stages of disease when the opportunity to preserve the retinal structure and visual function is greatest.

To address this urgent, unmet medical need, the researchers in this study innovated a systems pharmacology platform that leverages state-of-the-art disease modeling and characterization to identify novel, mechanism-based therapies that mitigate disease at the root cause. The SRED therapeutic intervention enhanced resilience to acute and chronic forms of stress in the degenerating retina, thus preserving tissue structure and function across multiple models of age-related or inherited retinal disease. Taken together, these findings exemplify a systems pharmacology approach to drug discovery and development, revealing a new class of therapeutics with potential clinical utility in the treatment or prevention of the most common causes of blindness.

“SREDs represent a promising strategy for patients and clinicians to combat disease in earlier stages with superior efficacy over the current standard of care, augmenting the arsenal of ophthalmic medications presently available in anti-angiogenics, corticosteroids, and nonsteroidal anti-inflammatory drugs (NSAIDs),” said lead author Jennings Luu, MD/PhD Doctoral Fellow of Pharmacology in the Medical Scientist Training Program at Case Western Reserve University and Visiting Scholar at University of California, Irvine. “Ultimately, it is our expectation that SREDs will someday serve as a standard of care for human aging, effectively providing patients the means to diminish suffering from debilitating ailments for which there currently exist no viable therapeutic options, thereby extending human lifespan and healthspan irrespective of disease etiology.”

This study was funded in part by the National Institutes of Health, the US Department of Veterans Affairs, the International Centre for Translational Eye Research project, and Research to Prevent Blindness.

Predicated in part on the discoveries highlighted in this publication, Luu and Palczewski have co-founded a seed-stage startup pharmaceutical company, Hyperion Therapeutics, Inc., which aims to commercialize the intellectual property associated with their recent discoveries and introduce to the market new therapeutic agents for the treatment or prevention of AMD, DR, RP, and other progressive, incurable blinding diseases. The Company was recently awarded first place in the Morganthaler-Pavey Startup Competition hosted by the Veale Institute for Entrepreneurship and has additionally partnered with UCI Beall Applied Innovation in the Wayfinder Incubator Program; through this strategic alliance, Luu and Palczewski are serving as co-investigators on a newly awarded Proof of Product grant, which will support the advancement of their pipeline therapies toward clinical trials and eventual commercialization.

A smart contact lens is a product attached to the human eye like a normal lens and provides various information. Research on the lens is being conducted mainly on diagnosing and treating health. Recently, Google and others are developing smart contact lenses for displays that can implement AR. Still, many obstacles to commercialization exist due to severe technical challenges.

In implementing AR with smart contact lenses, electrochromic¹⁾ displays that can be driven with low power are suitable, and “Pure Prussian Blue” color, with high price competitiveness and quick contrast and transition between colors, is attracting attention as the lens’ material. However, in the past, the color was coated on the substrate in the form of a film using the electric plating method²⁾, which limited the production of advanced displays that can express various information (letters, numbers, images).”

The achievement of KERI-UNIST lies in the fact that it is a technology that can realize AR by printing micro-patterns on a lens display using a 3D printer without applying voltage. The key is the Meniscus of used ink. The Meniscus is a phenomenon in which a curved surface is formed on the outer wall without water droplets bursting due to capillary action when water droplets are gently pressed or pulled with a certain pressure.

Prussian blue is crystallized through solvent evaporation in the Meniscus formed between the micronozzle and the substrate. The meniscus of the acidic-ferric-ferricyanide ink is formed on the substrate when the ink-filled micronozzle and substrate come in contact. Heterogeneous crystallization of FeFe(CN)6 occurs on the substrate within the meniscus via spontaneous reactions of the precursor ions (Fe3+ and Fe(CN)3−) at room temperature. Simultaneously, the solvent evaporation is occurred at the meniscus surface. When water evaporates from the meniscus, the water molecules and precursor ions move toward the meniscus surface by convective flow, generating a preferential accumulation of the precursor ions in the outer part of the meniscus. This phenomenon induces the edge-enhanced crystallization of FeFe(CN)6; this is crucial for controlling the factors that influence the crystallization of FeFe(CN)6 in the printing step to obtain uniformly printed PB patterns on a substrate. As with conventional electroplating, the substrate used to have to be a conductor when voltage was applied, but a great advantage of using the meniscus phenomenon is that there is no restriction on the substrate that can be used because crystallization occurs by natural evaporation of the solvent.

Through the precise movement of the nozzle, the crystallization of Prussian blue is continuously performed, thereby forming micro-patterns. Patterns can be formed not only on flat surfaces but also on curved surfaces. The research team’s micro-pattern technology is very fine (7.2 micrometers) that can be applied to smart contact lens displays for AR, and the color is continuous and uniform.

The main expected application area is navigation. Simply by wearing a lens, navigation unfolds in front of a person’s eyes through AR. Games such as the popular “Pokemon Go” can also be enjoyed with smart contact lenses, not smartphones.

Dr. Seol Seung-Kwon’s of KERI said, “Our achievement is a development of 3D printing technology that can print functional micro-patterns on non-planner substrate that can commercialize advanced smart contact lenses to implement AR.” He added, “It will greatly contribute to the miniaturization and versatility of AR devices.”

The related research results were recently published as a cover articler in Advanced Science (IF 17.521/JCR 4.71%), a world-renowned academic journal in the field of materials science, in recognition of its excellence.

The research team believes that this achievement will attract a lot of attention from companies related to batteries and biosensors that require micro-patterning of Prussian blue as well as the AR field, and plans to find related demand companies and promote technology transfer.

Meanwhile, KERI is a government-funded research institute under the Ministry of Science and ICT’s National Research Council for Science and Technology. Dr. Seol Seung-Kwon is also a professor at the KERI campus of the University of Science and Technology (UST). <KERI>

1) Electrochromism: a phenomenon where the color of a substance changes reversibly due to an electrochemical reaction.

2) Plating is the process of applying a thin layer of another metal to improve the surface condition of an object. In this process, if electrical energy is used, it is called “electroplating,” and if chemical reactions are utilized without electricity, it is referred to as “electroless plating.” Particularly electroplating is mainly used in the production of jewelry such as rings.