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eye to eye news August 2024 CONTINUED ON BACK PAGE MESSAGE FROM THE PRESIDENT Dear Readers, On June 8, in conjuncon with Evolve Medical Educaon, TGF held its second biennial medical symposium offering accredited connuing educaon to ophthalmologists and optometrists across the country. Eighty eye-care professionals joined us in person at the New York City Bar Associaon for a day of presentaons by experts from Harvard, Columbia, UC San Diego, SUNY, Mount Sinai, and the University of Miami. Close to 300 others aended the symposium on Zoom from throughout the U.S. as well as Brazil, Iran, Israel, Lebanon, Mexico, Nigeria, and Peru. Titled “Glaucoma – What I Do,” the presentaons by disnguished glaucoma professionals delved into diagnosis, therapies, the use of AI, and other hot topics in glaucoma care. I thank our partners Alcon, Bausch & Lomb, Théa Pharma, Glaukos, Sight Sciences, Ora, and Topcon for supporng this project. Very special thanks as well to our three Symposium co-chairs: Murray Fingeret, OD, Louis R. Pasquale, MD, FARVO, and Robert N. Weinreb, MD. NEW WEBINAR The Johnson Laboratory at the Johns Hopkins Wilmer Eye Instute has spent the past 5 years working to develop stem cell therapies capable of regenerang the opc nerve and restoring vision for paents suffering from glaucoma. This is a challenging goal since it requires the replacement of lost nerve cells in the eye and the building of new connecons between these stem cell-derived neurons and the paent’s own cells in the rena and the brain. On August 28, following up on last year’s TGF webinar, Dr. Johnson will present on the developments from his research — showing that human neurons are able to form new connecons with the recipient rena aer being transplanted into the eye. This advance represents a major step forward towards developing new treatments for reversing blindness in paents with glaucoma. The Glaucoma Foundation | Page One
The Glaucoma Foundation | Page Two During the June TGF Symposium’s session on Diagnosing and Monitoring of Glaucoma, Dr. Janey L. Wiggs discussed using genecs as a management tool for glaucoma. Dr. Wiggs is the Paul Ausn Chandler Professor of Ophthalmology and vice chair for clinical research in ophthalmology at Harvard Medical School. She specializes in the genecs of glaucoma. “Genecs is a tool that we should be using hand in hand with all our other clinical tools,” she began. “Glaucoma is actually one of the most heritable of all human condions, she explained, so it’s very helpful that there are so many risk variants – that genecs are so strong for the disease – that we can capitalize on this associaon.” Dr. Wiggs discussed both early-onset and adult-onset glaucoma. There are currently 12 genes that are known to cause early-onset condions, like congenital glaucoma, which is usually present in children and caused by rare mutaons in genes that have very large effects. As a result, those mutaons are transmied in families and tesng can be very important because everyone in the family who has this mutaon can be idenfied. This genec informaon is also useful to inform eye to eye news GENETICS AND GLAUCOMA Janey Wiggs, MD, PhD
The Glaucoma Foundation | Page Three eye to eye news genec counseling, for example when a family is considering having another child. Unfortunately, currently these 12 genes only account for about 20 percent of paents under the age of 40. A lot of work is going on to idenfy new genes. Adult-onset glaucoma is a different maer, with complex inheritance, meaning that a single gene variant is not sufficient to cause disease. But as an aggregate with other gene variants and in some cases with environmental condions, the disease threshold can be reached. Over 127 genes that can contribute to primary open-angle glaucoma have been idenfied. Individually they have small effects so it doesn’t make sense to test one of them at a me. Instead, Dr. Wiggs explained, one needs to test a group of them to see what kind of genec burden a person has for these variants that have been discovered. If you take all the variants found in a person, then add them up and determine where that person ranks among a community of people, the one with the highest number has the highest polygenic genec risk. Studies are showing that those with the highest risk factor have earlier diagnoses, thinner fiber layer thickness, and a greater need for surgical intervenon to control progression. A study now underway is calculang the polygenic genec risk factor for two populaon groups in New York and Boston totaling 90,000 people. Among findings, the study has found that people with high polygenic risk scores had a higher prevalence of glaucoma by almost 35 percent. And half of the people idenfied with glaucoma among the high-risk group were previously undiagnosed. The only reason they were diagnosed was because they entered the study. “In terms of adult-onset paents who are at high polygenic genec risk, we can show that this is potenally a useful screening tool,” Dr. Wiggs concluded. “Those are the people we should bring into our clinics for more in-depth tesng using our definive tools.” Your donaons maer. Since it’s founding in 1984, The Glaucoma Foundaon has never wavered from its principle goals to fund cung edge glaucoma research and to educate the public about glaucoma. Your contribuons provide us with the resources to deliver on our mission. Thank you for giving.
The Glaucoma Foundation | Page Four A Patient’s Experience eye to eye news eye to eye news “I made an appointment,” Heather explains, “and we did all the tesng. Sure enough, they said my IOP was high and found that I had some vision loss. But I connued to get headaches, which ended up being from blocked tear ducts. That was about a year later and I got immediate relief. I had a few laser procedures but my visual field tests kept geng worse and I was losing vision. Eye drops didn’t help either. So I kept going from doctor to doctor, asking ‘can you tell me what’s going on here?’ “Finally, in 2022, I was diagnosed with Plateau Iris Syndrome. It’s sll involves glaucoma and higher IOP but it’s about things that weren’t being addressed. Plateau iris is an uncommon anatomical variant that predisposes a paent to primary angle-closure glaucoma. An ultrasound of my eye confirmed the diagnosis, and surgery was scheduled for a few months later. The surgery had two elements -- during cataract surgery, while the lens was removed, they used a Kahook Dual Blade and a laser to basically change the anatomy of my iris so everything can flow. Today, over a year later, my pressures are down to 10 in each eye, and at my last visual field test my doctor said there was very lile change --which was great news. I’m sll on glaucoma meds as a precauon. “Since my surgery I am very light sensive. I had to give up my wedding invitaon business as I worked at a computer all day and I can’t sit at a screen for that long anymore. Now I work part me for a friend who has a wedding planning business. I love it. It’s just a few hours a day “It’s been a long process, six or seven years and so many doctors, “says Heather Dempsey, speaking about being diagnosed with Iris Plateau Syndrome in 2022. For years before that Heather felt that something was wrong but that she didn’t have the right diagnosis. “I kept listening to that lile inner voice and just kept going from doctor to doctor to doctor unl I found the right one.” Heather, who lives north of Atlanta, was 41 when she started having headaches in 2017 and thought she might need glasses. So she went to her optometrist and had her vision checked. The optometrist recommended an image of her opc nerve, just to have it as a baseline. She did that immediately, and her doctor said she probably had glaucoma and should really see an ophthalmologist.
The Glaucoma Foundation | Page Five eye to eye news Felipe A. Medeiros, MD, PhD Professor of Ophthalmology Vice Chair of Research Bascom Palmer Eye Instute Although there have been a lot of developments in AI, bringing them to real-world glaucoma clinical sengs has actually been quite slow. One reason for the complexity in implemenng AI in medical pracce is the extensive regulatory framework. For instance, considerable research has focused on enhancing opcal coherence tomography (OCT) imaging for glaucoma diagnosis using AI, including work conducted in my lab and others. However, beyond developing these AI models, there are addional steps required for clinical integraon. To deploy these models on diagnosc devices, companies must conduct comprehensive clinical trials to meet FDA requirements, ensuring the algorithms are both safe and effecve. One area where AI is being adopted more rapidly is in quality assessment and improvement. Much like AI enhances photo quality on smartphones, it can also enhance the quality of images and tests in devices used for glaucoma assessment. The regulatory requirements for such supporve applicaons tend to be less stringent than those for direct diagnosc tools, facilitang faster integraon into clinical pracce. and just enough. My 89-year-old Dad lives with us and it’s a blessing to spend me with him. “But eventually I would love to do something involved with glaucoma because I feel very passionate about it. I always tell my family to visit the ophthalmologist and get images of their opc nerves because you won’t always know what’s going on. My body just went ‘something’s wrong.’ If I hadn’t had those clogged tear ducts I don’t know when I would have noced that I was losing vision. “Some things just weren’t noced. This syndrome is more common in younger female paents in their 30s and 40s. I’m a 48-year-old now. I also have central vision loss rather than peripheral –another indicator for iris plateau syndrome. I know there are so many different types of glaucoma but I wish a doctor had taken note of that earlier. “I’m just so glad that I did find the right doctor – if someone is not heard, you have to kind of take the reins and keep going. “I am lucky to have the vision that I have now – using both eyes together, it’s not bad enough to affect my life. But if I’m looking at a computer screen for something small, like a period or a short word, I’ll be like ‘I know it’s there but where is it.’ Not knowing what will happen in the future is very stressful and it does take an emoonal toll. I find meditaon to be very helpful.” CONTINUED ON BACK PAGE USING AI IN CLINICAL PRACTICE
The Glaucoma Foundation | Page Six eye to eye news Expanded Focus and Increased Funding for Research Since its founding, TGF’s Grant-in-Aid Program has awarded millions of dollars in seed money for cung-edge research projects. Preliminary data from these projects have frequently been used to support proposals for larger grants from such enes as the Naonal Instutes of Health. Beginning with the current 2024 funding cycle, one-year TGF grants of up to $75,000 are being made in the areas of Exfoliaon Syndrome and Exfoliaon Glaucoma, Pressure Independent Mechanisms of Glaucoma, Neuroprotecon, and the Genecs of Glaucomas that affect people under the age of 40. Three researchers are the first to be funded under the new guidelines. Markus H. Kuehn, PhD, Professor in the Department of Ophthalmology and Visual Science at the University of Iowa, will examine the “Role of the Immunoproteasome in Glaucoma Neuroinflammaon.” Autoimmune reacons can develop during the disease, resulng in slow but chronic vision loss. Highly specific inhibitors of this complex exist and have been shown to reduce damage in other neurodegenerave diseases The proposal aims at demonstrang that acvaon of the immunoproteasome worsens glaucoma, providing strong support for the development of novel medical treatments. Ursula Schloetzer-Schrehardt, PhD, Professor of Experimental Ophthalmology at the University of Erlangen-Nürnberg, will examine an “Advanced in Vitro Model for Pseudoexfoliaon Syndrome and Glaucoma.” Pseudoexfoliaon (PEX) syndrome is frequently associated with a severe form of glaucoma, which is believed to result from an accumulaon of an abnormal fibrillar matrix product. Currently there is limited informaon about the mechanism leading to the producon of PEX material. A major limitaon to developing specific therapies is the lack of experimental models. This grant will be used to connue invesgang the potenal of using cells from small iris ssue specimens rounely obtained during glaucoma surgery in PEX paents to develop a cell culture model for the disease. Yang Sun, MD, PhD, Professor of Ophthalmology, Stanford University, “Targeng Primary Cilia Signaling for Glaucomatous Opc Neuropathy.” In glaucoma, cells in the rena and opc nerve deteriorate over me. Sciensts are exploring the role of cilia in promong the growth of nerve cells and improving how the rena responds to light. In this lab, researchers are studying live mice to understand how changes in eye pressure affect the cilia signaling of nerve cells in the rena to shed light on how cilia could help protect the opc nerve from damage.
The Glaucoma Foundation | Page Seven eye to eye news DRIVING WITH GLAUCOMA Are Car Headlights Getting Brighter? Light sensivity and glare are common problems for people with glaucoma. Many glaucoma paents choose to avoid night driving due to the headlight glare that makes is difficult to see well. And today’s car headlights are geng brighter; it’s not your imaginaon. The newer LED headlights produce a more focused and higher-intensity light beam than their halogen predecessors, so they’re perceived as much brighter. While this technology has greatly enhanced safety by helping drivers idenfy obstacles, pedestrians, and road signs more easily, it has come at a cost — blinding other drivers. The proliferaon of SUVs and large pickup trucks with headlights posioned higher off the ground than sedans and smaller cars has also contributed to the problem. The height of these vehicles means the headlights are more aligned with the eye level of drivers in standard-height cars, which can increase the intensity of light that reaches their eyes. For glaucoma paents, warning signs that driving may be dangerous include: loss of peripheral vision (making it difficult to see and react in me to avoid obstacles like other cars and pedestrians coming from the side); blurred vision (making it harder to disnguish clear images and see movement such as passing cars or someone crossing the street); increased light sensivity, (making it more difficult for your eyes to adjust from headlight glare at night); and close calls (because of a failure to noce obstacles in the road).
eye to eye news MESSAGE FROM THE PRESIDENT connued from page 1 These excellent talks will be posted on our YouTube channel every Tuesday and we will be spotlighng some of them in our newsleers, beginning in this issue with Dr. Janey Wiggs’ presentaon on genecs and glaucoma. Our most recent webinar (also posted on our YouTube channel) introduces us to a new federal health agency, ARPA-H, that is bringing together sciensts from mulple universies and laboratories to restore vision in the blind. Using recent advances in regenerave medicine and biomaterials, they hope to reconnect nerves and blood vessels and achieve the funconal transplantaon of a donor eye. youtube.com/@theglaucomafoundaon Thank for your ongoing support for TGF’s programs, fellowships, and research grants. Wishing you all the best, Elena Sturman esturman@glaucomafoundaon.org 212 651 1900 We hope that find this newsleer informave. If you’d like to suggest an arcle for the future, please let us know. info@glaucomafoundaon.org The Glaucoma Foundation | Page Eight For example, when you acquire an image of your rena with OCT for the purpose of evaluaon for glaucoma, you are interested in looking at specific features, like measuring the thickness of the nerve fiber layer. The OCT soware must then segment the different layers of the rena to obtain such thickness measurements. This can be done much beer with AI compared to the older algorithms There is also a lot of work being done in the area of screening, trying to come up with AI that could be made widely available – for example based on simple photographs of the back of the eye to idenfy glaucoma. While there are commercially available machines approved by the FDA that can be used for screening of diabec renopathy, this has proven harder for glaucoma. One of AI’s strengths lies in its ability to idenfy paerns, parcularly useful in interpreng images and visual field tests for glaucoma management. AI can streamline this process by analyzing the data more objecvely, enhancing the precision and efficiency of glaucoma diagnosis and monitoring. While there is ongoing progress in developing these decision-support systems, and their promise is undeniable, several challenges sll need to be overcome before AI can be fully integrated and adopted into clinical pracce. The process is underway, but it will take me. edited from the original arcle USING AI connued from page 5