2019 Weston Glaucoma Research Lecture by Terri Pickering, MD

Lecture Transcript

Andrew Iwach, MD: Thank you for joining us tonight. My name is Andrew Iwach, and I’m honored to serve as board chair for the Glaucoma Research Foundation. It is a pleasure to welcome you here this evening to the Daniel Scott Weston Glaucoma Research Lecture. Each year, we look forward to this opportunity to meet with our friends and supporters, and highlight recent advances in glaucoma research. Thank you for being with us here this evening. Glaucoma is the leading cause of irreversible blindness worldwide. The Glaucoma Research Foundation’s mission is to cure glaucoma and restore vision through innovative research. The Glaucoma Research Foundation has been an incredible catalyst in advancing the agenda for glaucoma research. Thanks to this investment and dedication, there are now many more options to help patients who are affected by glaucoma.

This year, we have selected our newest team of researchers for the Catalyst for a Cure campaign, and we’re very proud of them. You’ll be learning more about their work through tonight’s program. We also are incredible grateful to our many generous donors and dedicated volunteers who join us on this important mission. Thank you for your ongoing partnership. Tonight’s event was made possible through the remarkable support of Gladys and George Weston. Through their generosity, they established this lecture in memory of their beloved son Danny. Thank you both very much for doing this.

Gladys Weston: You’re very welcome.

Andrew Iwach: It is wonderful to have George and Gladys’s daughter Jane Weston here, as well as Jan Horn. Thank you for also being here with us this evening. I’m so pleased that Dr. Terri Pickering will be our featured speaker this evening. Dr. Pickering will highlight some of the recent research as well as potential impact on glaucoma patients. Terri is a dear friend. She has been a colleague of mine at the Glaucoma Center of San Francisco since 2001. She received her medical degree from Harvard University, and then went on to do her ophthalmology residency here in San Francisco at UCSF. After finishing her glaucoma fellowship at USC Doheny Eye Center in Los Angeles, she moved back to San Francisco where she now practices with us.

Terri is an outstanding clinician. She is a clinical instructor at CPMC in San Francisco. She’s also a researcher with the Glaucoma Research and Education Group in San Francisco. Over the past 18 years, she has also served as a physician volunteer for EyeCare America. Terri’s clinical interests and research interests include selective laser trabeculoplasty, also known as SLT, various types of drainage devices, and ocular imaging for managing glaucoma patients. With that, it’s now my pleasure to introduce Doctor Terri Pickering to the podium.

Terri Pickering, MD: Good evening, everyone, and I really want to thank you all for coming out this evening on a school night as it were, to join me and the Glaucoma Research Foundation for this discussion this evening. More so, I’d like to thank the Weston Family for their incredible generosity. I want to thank them for the opportunity to honor their son, and such a fine person was their son. So, thank you very much, and it’s a pleasure to see you all here this evening. So, I’m going to talk a little bit about glaucoma, and it’s important to have a bit of a historical perspective. Why is glaucoma called glaucoma in the first place? It’s something that always puzzled me. Basically, it’s from the early Greek glaukos, meaning shimmering or gleaming, and the meaning evolved over time to describe a sea-green color of eyes that were affected, especially in historical time before treatment was available. Descriptions of glaucoma date back to the writings of Hippocrates and surgical treatment dates back to 1848. There was an obscure procedure called corneal puncture.

Medications actually came about later, and they date back to 1878, and the first medication was something called physostigmine. So since 1848, we’ve been looking at ways to treat patients with glaucoma, look at ways to help preserve vision, so the question is, where are we today? Well, there’s been another great surge in treating and caring for glaucoma, and it’s been brought about by the Glaucoma Research Foundation, their unique approach to research called “Catalyst for a Cure.” This is completely developed by the Glaucoma Research Foundation. It’s their baby, their creation, and what it does is bring together four different labs with a mandate to collaborate. They have to cooperate with each other. The goal is to create science that’s greater than the sum of its individual parts through original research, and these scientists only receive funding if they prove that they have collaborated together. Collaboration is key, and they also have to have progress, of course, toward annual goals.

This unique approach to research was created by the Glaucoma Research Foundation in order to accelerate the pace of discovery toward a cure for glaucoma. It brings together these different scientists with diverse backgrounds and different skill sets to work together and find innovative ways to better understand glaucoma and treatment, and ultimately the final goal, the ultimate goal, which is to find a cure. This is really unusual because typically in the US, and even internationally, individual scientists work separately, and they’re in competition for the same pool of money, the same set of funding. So, this is different because instead of competing with each other, these Catalyst for a Cure scientists actually work together, and this causes the science to progress more rapidly, and they move together more quickly toward a cure. This is important because it relates to me, and my practice with my patients.

One of my patients is a 38-year-old mother of two. She’s pregnant with her third child, and she was fortunate in the sense that she was diagnosed at 17. The reason why this is fortunate is that most teenagers, the last thing they have on their mind is going to the eye doctor, or going to get glasses, or going to any doctor at all. She went because she had already had visual field loss, and she noticed it. That’s how severe the glaucoma was at the young age of 17. In fact, so severe that her diagnosing physician told her, “Just looking at what I see today, you’ll probably be blind by the age of 30.” This has always haunted her and she told me this when we first met, and she’s been in our practice for many years and unfortunately, she has sustained relentless visual field loss despite multiple lasers and multiple surgeries. She even underwent glaucoma surgery in the operating room while pregnant because her pressure shot up and could not be controlled medically. Because of the pregnancy, she underwent the surgery without any sort of sedation.

She’s devoted to her family, she’s devoted to saving her vision. She’s really devoted to do anything she can to help save her sight, and one of the questions she asked is, “Why is my glaucoma so severe? Is it inevitable? Because, this doctor told me when I was 17 that I will go blind.” So, it’s patients like this that really motivate me and the researchers at GRF to do what we can to help them, and the first team for Catalyst for a Cure was founded in 2002. They were together for 10 years, and their focus was what this patient was asking about. What is the mechanism of glaucoma progression? They had expertise in neurobiology, ophthalmology, physiology, developmental genetics, and the research eventually ended up focusing on neuroprotection. How can we further protect the optic nerve from more damage?

This cross disciplinary research targeted retinal ganglion cells in their axons. So, retinal ganglion cells are actually the cells that are in the optic nerve. They actually are what the optic nerve is made of. So, they want to get down to the basic science. How do we protect these special retinal ganglion cells that comprise the optic nerve? They actually did contribute to a major national paradigm shift in thinking about glaucoma, because they found that degeneration involves oxidative stress. That was thought but not really confirmed, and they definitely confirmed that. Inflammation, that’s a buzzword in all of medicine today, and a decrease in metabolic resources. They also redefined how glaucoma research is being conducted now. This led to the establishment of the National Eye Institute’s Audacious Goals Initiative, focusing on restoring vision through regeneration of the retina and these special retinal ganglion cells, and it is now a national priority in the United States. So thanks to the Glaucoma Research Foundation, we’ve had a shift in what research is focused on throughout the whole United States.

Moving on to my patient, she’s afraid of the future. She has two children, a beautiful family, and she wants to know, “Will my children ultimately get glaucoma?” This leads to the biomarker initiative. This was the second group for the Catalyst for a Cure, and those researchers worked together from 2012 to 2018. Their focus was to investigate ways to measure, detect glaucoma before vision loss occurs, and to identify possible new treatment targets. So, they developed new imaging technology to “see” retinal ganglion cells, and “see” is in quotation marks because in theory, every time I look at the retina or another doctor looks at the retina, we are looking at retinal ganglion cells. We need to look at them in very fine detail in order to actually see how they’re functioning. How are they metabolically? Are they alive, are they dead, are they at risk? We never had these tools before, and they are working toward that goal.

They identified several possible new biomarkers, and they’re now focusing on the three most promising, and these have actually come to the point where they’re being used in clinical trials to restore vision. Getting back to my patient, what really make her strike home with me and touch my heart is that she’s a physician. She’s busy, she works as a doctor. She sees lots of patients a day, and she wants to know at 38, will she be able to work until she’s ready to retire and help support her family? Will she be able to see her children graduate from college? The reason I have the photo next to the slide is that is an example. It’s not hers, but it’s an example of what her optic nerve looks like, and she already at the age of 38 has a lot of glaucoma damage. So when someone is that young, that level of glaucoma damage, it makes me very worried because it is very challenging to preserve the nerve with 30, 40, even 50 years of life to live.

This is where the next step comes in. What can we do for patients who’ve already lost vision from glaucoma? This next step is vision restoration. It is audacious, and it has not been really the focus of glaucoma treatment or research in prior decades in this country, but based on the success of the first two Catalyst for a Cure consortiums, the Glaucoma Research Foundation launched this phase of research in 2019 to focus on restoring vision. Leading experts in neuroregeneration have been brought together to serve on the scientific advisory board, and helping out an elite team of researchers to work collaboratively to try to find novel ways to actually restore vision loss to glaucoma. We’ve not been able to do that yet with any of our medications or surgeries.

This is our new team, Dr. Duan, Dr. La Torre, Dr. Hu, and Dr. Welsbie. Dr. Duan’s lab investigates the retinal ganglion cells, those are the cells that actually make up the optic nerve body, and they look at factors that are intrinsic to those cells and test their roles in regeneration and vision recovery. In other words, are there factors within the cells themselves that can help their own regeneration? Dr. Hu’s lab focuses on how neurodegeneration happens and how do these nerve cells regenerate their axons? His focus looks at scenarios and therapies that can translate into restoration, looking at how they degenerate in the first place, and how axons may be able to regenerate and regrow themselves.

Dr. La Torre’s lab looks at generating retinal ganglion cells from stem cells, and this is very exciting. There’s a lot of promise there, and looking at ways to enhance these cells growing into axons and to enhance their cell survival. So, how do we make new retinal ganglion cells from stem cells, which have the potential to make any number of different cells? Hopefully the goal is to use these donor cells a replacement therapies for patient who need them. Then last but not least, Dr. Welsbie’s lab focuses on looking at the genes that cause retinal ganglion cell death. Why do some patients start to have their retinal ganglion cells die at 17, others at 34, and others not until 70? What genes are being turned on within their eyes that are causing what we consider this pre-programmed cell death? So, he’s looking at trying to understand this very intrinsic process, and then coming up with new therapies to stop this, prevent it, or even heal it.

We’re excited for this team because their goals are to focus on restoring the optic nerve, repairing the optic nerve, and actually rebuilding some day and regrowing optic nerves. Already, even though the team only got together this year, there is a milestone. They’ve been able to label retinal ganglion cells, and when we look at the retina, we look at your eye, we just see a lot of tissue. A lot of cells all mixed in together. This labeling allows us to identify these specific cells in the cell layer, and it would allow us to develop a tissue in the way of monitoring response to medication, response to treatment and look at if they’re being reproduced and how they’re surviving over time using live imaging technology, which is new. We haven’t been able to do that before. The slide on the left basically shows the optic nerve in the center, which is the dark area, with lots of green tendrils radiating out of it. They’re actually radiating into the nerves. Those are the ganglion nerve cells feeding into the optic nerve, so we’re actually able to identify these and observe them in real time in real life.

This is another milestone, growing retinal ganglion cells in the lab, and this is crucial. If we can grow new retinal ganglion cells in the lab, we may be able to grow new retinal ganglion cells in patients. It’s obviously not ready for prime time, it’s still at the lab stage, but so far they have been able to use stem cells to generate three dimensional little clusters of cells that are called organoids. These are small tissue aggregates of cells that contain all the different cells of a retina, including the retinal ganglion cells that are depicted in green. So, we’re trying to actually rebuild functional ganglion cells to heal the optic nerve and maybe even retina tissue, full thickness retinal tissue. This is very exciting.

Another milestone that’s being worked on is that there’s been discovery of a new strategy to increase the survival of the cells that compose the optic nerve, the retinal ganglion cells, and a way to promote their growth of new cells, new axons. The axons are the cells that connect the optic nerve to the brain, and the control shows an area of tissue where some of the cells have died. The treated slide shows more green, more highlights of new cells that have grown, and the cell survival has been enhanced. The other milestone that we’re hoping to accomplish is transplanting cells. Wanting to view individual cells, follow their development over time, and actually see if we can integrate into a living optic nerve in the correct way. It’s one thing to be able to grow cells in the lab or in a tissue culture, but to be able to introduce them into the patient’s vitreous or retina in some way and have them go to the correct place and function correctly, that’s another issue. So if we can transplant viable cells, that would be fantastic.

The researchers met in early August [2019] to report on their first six months of working together, and so far it’s been outstanding. They visited each other’s lab to share ideas and materials, and they’ve had some key accomplishments. One is creation of new tools to identify the different type of retinal ganglion cells, there are multiple type that make up the optic nerve, and how they transmit visual images from the retina to the brain. Another key accomplishment is developing screening techniques to allow different types of cells to be collected, and there was a big unexpected discovery. A new strategy, new technique, that not only increased the survival of retinal ganglion cells, but also promoted the growth of new axons, which are the long endings, the tail endings of these cells that make up the optic nerve and take the information from the eye to the brain. This was unexpected and is very exciting, so we’re very happy that even as early as August, there’s been a new discovery.

So in just eight months, they made some significant discoveries. There are more discoveries to follow, and the investigators are going to meet again in February of 2020 here in San Francisco, and they’re going to review their progress and outline their approach for the second year. So please stay tuned for future developments. Then in terms of family history, this is why we do what we do. This is why we work every day and see patients. We want to preserve sight. We want to really take care of our patients, and we want our patients to be able to see their children graduate, thrive, be happy, enjoy their own careers, and enjoy their lives, and maintain vision. Functional, useful vision throughout their lifetimes. This is where the Glaucoma Research Foundation comes into play. This organization has really made a serious long-term commitment to collaborative research, unlike any other organization in the United States, frankly. The Catalyst for a Cure initiative and the scientists it’s brought together are our best hope for finding a cure for this devastating disease.

The days of individual researchers working in isolation, that’s still important, but collaboration has been shown to really excel great progress so much more. So, I really want to congratulate the Glaucoma Research Foundation in having the foresight, in leading the way in this new era for glaucoma treatment and the hope of finding a cure. Thank you.

End transcript

First posted on March 5, 2020; Reviewed on May 13, 2022