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Message JULY 2024 NEWSLETTERGenetics and GlaucomaRecent Research GrantsMeet Heather DempseyHeadlights on the RoadAugust Webinar

Newsletter July, 2024MESSAGE FROM THE PRESIDENTDear Readers,We ended our busy spring season on June 8 when TGF, in conjunction with Evolve Medical Education, held its second medical symposium oering accredited continuing education to ophthalmologists and optometrists across the country. Some 80 eye-care professionals joined us in person at the New York City Bar Association for a day of presentations by experts from such institutions as Harvard, Columbia, UC San Diego, SUNY, Mount Sinai, and the University of Miami. Close to 300 others attended the symposium on Zoom from throughout the U.S., as well as from Brazil, Iran, Israel, Lebanon, Mexico, Nigeria, and Peru.Titled “Glaucoma – What I Do,” the presentations by distinguished glaucoma professionals covered such topics as diagnosis, therapies, the use of AI, and other hot topics. The goal was to bring optometrists together with ophthalmologists to explore the best possible treatment for glaucoma and inspire better patient care. I thank our partners Alcon, Bausch & Lomb, Théa Pharma, Glaukos, Sight Sciences, Ora, and Topcon for supporting 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.The excellent talks were informative and fascinating – you can access a new presentation from the symposium every Tuesday on YouTube The Glaucoma Foundation - YouTube or via our website. We will be spotlighting some of the talks in our newsletters, beginning in this issue with Dr. Janey Wiggs’ presentation on genetics and glaucoma.Also on YouTube and the website is the interesting webinar held in May, at which Calvin W. Roberts, MD, a Program Manager at the new federal health agency, ARPA-H, discussed their new program that aims to bring together the expertise of vision scientists from multiple universities and laboratories to restore vision by transplanting a donor eye to those who are blind.The next webinar in our ongoing series is scheduled for August 28, when Dr. Thomas Johnson will give an update on his optic nerve regeneration research.We wish all our readers a very happy July 4th holiday and a good summer. We thank each of you for your ongoing support that makes our work possible. With gratitude,Elena Sturman

Genetics and GlaucomaDuring the June TGF Symposium’s session on Diagnosing and Monitoring of Glaucoma, following presentations on visual elds, OCT, and IOP, Janey L. Wiggs, MD, PhD ended the session with her talk on using genetics as a management tool for glaucoma.Dr. Janey WiggsDr. Wiggs is the Paul Austin Chandler Professor of Ophthalmology and vice chair for clinical research in ophthalmology at Harvard Medical School. She specializes in the genetics of glaucoma.“Genetics 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 conditions, she explained, so it’s very helpful that there are so many risk variants – that genetics are so strong for the disease – that we can capitalize on this association.”Dr. Wiggs discussed both early onset and adult-onset glaucoma.There are currently 12 genes that are known to cause early-onset conditions, like congenital glaucoma, which is usually present in children and caused by rare mutations in genes that have very large eects. As a result, those mutations are transmitted in families and testing can be very important because everyone in the family who has this mutation can be identied. This genetic information is also useful to inform genetic counseling, for example when a family is considering having another child. Unfortunately, currently, these 12 genes only account for about 20 percent of patients under the age of 40. A lot of work is going on to identify new genes. Adult-onset glaucoma is a dierent matter, with complex inheritance, meaning that a single gene variant is not sucient to cause disease. But as an aggregate with other gene variants and in some cases with environmental conditions, the disease threshold can be reached.Over 127 genes that can contribute to primary open angle glaucoma have been identied. Individually they have small eects so it doesn’t make sense to test one of them at a time. Instead, Dr. Wiggs explained, one needs to test a group of them to see what kind of genetic 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 genetic risk. Studies are showing that those with the highest risk factor have earlier diagnoses, thinner ber layer thickness, and a greater need for surgical intervention to control progression. A study now underway is calculating the polygenic genetic risk factor for two population groups in New York and Boston totaling 90,000 people.

Newsletter July, 2024Among ndings, 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 identied 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 patients who are at high polygenic genetic risk, we can show that this is potentially a useful screening tool,” Dr. Wiggs concluded. “Those are the people we should bring into our clinics for more in-depth testing using our denitive tools.” LIVING WITH GLAUCOMAMeet Heather Dempsey“It’s been a long process, six or seven years and so many doctors, “says Heather Leason, 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 little inner voice and just kept going from doctor to doctor to doctor until 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 optic 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. “I made an appointment,” Heather explains, “and we did all the testing. Sure enough, they said my IOP was high and found that I had some vision loss. But I continued 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 eld tests kept getting 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 still 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 patient to primary angle closure glaucoma. An ultrasound of my eye conrmed 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 ow. Today, over a year later, my pressures are down to 10 in each eye, and at my last visual eld test my doctor said there was very little change --which was great news. I’m still on glaucoma meds as a precaution.“Since my surgery I am very light sensitive. I had to give up my wedding invitation 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-time for a friend who has a wedding planning business. I love it. It’s just a few hours a day and just enough. My 89-year-old Dad lives with us and it’s a blessing to spend time 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 optic 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 noticed that I was losing vision.“Some things just weren’t noticed. This syndrome is more common in younger female patients 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 dierent types of glaucoma but I wish a doctor had taken note of that earlier.“I’m just so glad that I did nd 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 aect 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 emotional toll. I nd meditation to be very helpful.” DRIVING WITH GLAUCOMA:ARE CAR HEADLIGHTS GETTING BRIGHTER? Light sensitivity and glare are common problems for people with glaucoma. Many glaucoma patients choose to avoid night driving due to the headlight glare that makes is dicult to see well. And today’s car headlights are getting brighter; it’s not your imagination.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 identify obstacles, pedestrians, and road signs more easily, it has come at a cost — blinding other drivers. The proliferation of SUVs and large pickup trucks with headlights positioned higher o 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.WARNING SIGNSFor glaucoma patients, warning signs that driving may be dangerous include: loss of peripheral vision (making it dicult to see and react in time to avoid obstacles like other cars and pedestrians coming from the side); blurred vision (making it harder to distinguish clear images and see movement such as passing cars or someone crossing the street); increased light sensitivity, (making it more dicult for your eyes to adjust from headlight glare at night); and close calls (because of a failure to notice obstacles in the road).

Newsletter July, 2024TGF Announces New Research Grants and an Expanded Focus and Increased Funding for its Grant-in-Aid ProgramBeginning with the current 2024 funding cycle, one-year TGF grants of up to $75,000 will be made in the areas of Exfoliation Syndrome and Exfoliation Glaucoma, Pressure Independent Mechanisms of Glaucoma, Neuroprotection, and the Genetics of Glaucomas that aect people under the age of 40.Since its founding, TGF’s Grant-in-Aid Program has awarded millions of dollars in seed money for cutting-edge research projects. Preliminary data from these projects have frequently been used to support proposals for larger grants from such entities as the National Institutes of Health.“We are pleased that we are able to broaden the scope and increase funding for our Grant-in Aid Program so that our eorts can have a still greater impact on our goal of eliminating blindness from glaucoma,” said Elena Sturman, President and CEO of the Foundation.TGF has announced the rst three researchers 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 Neuroinammation.” Autoimmune reactions can develop during the disease, resulting in slow but chronic vision loss. Highly specic inhibitors of this complex exist and have been shown to reduce damage in other neurodegenerative diseases The proposal aims at demonstrating that activation 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 Pseudoexfoliation Syndrome and Glaucoma.” Pseudoexfoliation (PEX) syndrome is frequently associated with a severe form of glaucoma, which is believed to result from an accumulation of an abnormal brillar matrix product. Currently, there is limited information about the mechanism leading to the production of PEX material. A major limitation to developing specic therapies is the lack of experimental models. This grant will be used to continue investigating the potential of using cells from small iris tissue specimens routinely obtained during glaucoma surgery in PEX patients to develop a cell culture model for the disease.Yang Sun, MD, PhD, Professor of Ophthalmology, Stanford University, “Targeting Primary Cilia Signaling for Glaucomatous Optic Neuropathy.” In glaucoma, cells in the retina and optic nerve deteriorate over time. Scientists are exploring the role of cilia in promoting the growth of nerve cells and improving how the retina responds to light. In this lab, researchers are studying live mice to understand how changes in eye pressure aect the cilia signaling of nerve cells in the retina to shed light on how cilia could help protect the optic nerve from damage.

WEBINARBUILDING CONNECTIONS: Research progress in vision-restoring therapy for glaucomaJoin us live on Wednesday, August 28for a webinar with Thomas V. Johnson, MD, PhD. The Johnson Laboratory at the Johns Hopkins Wilmer Eye Institute has spent the past 5 years working to develop stem cell therapies capable of regenerating the optic nerve and restoring vision for patients suering from glaucoma. This is a challenging goal since it requires replacement of lost nerve cells in the eye and the building of new connections between these stem cell-derived neurons and the patient’s own cells in the retina and the brain. Following up on last year’s TGF webinar, Dr. Johnson will present new and exciting developments from his research, showing that human neurons are able to form new connections with the recipient retina after being transplanted into the eye. This advance represents a major step forward towards eventually developing new treatments for reversing blindness in patients with glaucoma.

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