In this episode of Retina Mentor Moments, John Kitchens, MD is joined by Theodore Leng, MD, MS, FACS—Director of Clinical and Translational Research at Stanford University School of Medicine—to discuss Dr. Leng's career and research, specifically his pioneering work in artificial intelligence (AI) and stem cell therapy in ophthalmology.
Dr. Leng’s career evaluating the role of artificial intelligence in ophthalmology
Dr. Leng’s educational background and mentorship include working with Mark Blumenkranz, MD, MMS, a renowned figure in retinal research, at Stanford, and participating in initial laboratory experiments that eventually led to the approval of the Pattern Scanning Laser (Pascal).
He recalls over a decade of experience in AI, beginning in 2016 with using it to analyze OCT images for tracking geographic atrophy (GA). Recently, Dr. Leng helped develop EYE-Llama, an open-source large language model fine-tuned for ophthalmology that can answer medical questions and describe OCT findings.
“Meta decided to make their large language model open source for the hobbyist or the scientist to play with, and so we decided to play with it. We used that base model, and then we kind of tuned it using ophthalmology data. We had experts grade different questions or other areas of ophthalmology-specific language and use that to fine-tune the Llama model,” Leng said.
“Then we did experiments to answer basic ophthalmology questions like, for example, ‘What is glaucoma?’ or ‘What's the risk of me getting retinopathy if I have diabetes?’ and it performed really, really well, which was exciting.”
Moreover, “An AI could save you a few seconds, for example, if it pre-examined your OCT image from today and compared it to the last one and told you if there was new fluid; these seconds add up over a busy day of retina clinic and could also reduce your cognitive load,” Dr. Leng added.
Deeper dive into cell therapy research
Currently, he is focused on stem cell therapy for vision restoration, as it replaces the dead or dying cells, unlike current complement inhibitors that only slow vision loss. He is the principal investigator for clinical trials on subretinal stem cell transplants, with early data showing that some patients have gained up to 28 letters of vision.
Cell therapy, specifically cell-based therapy for the treatment of geographic atrophy, is a primary area of research for Dr. Ted Leng. It involves repairing or replacing damaged tissue by carefully manipulating and guiding healthy donor cells. In age-related macular degeneration (AMD), clinical trials are exploring the transplantation of retinal pigment epithelium (RPE) cells as a form of treatment.1
Current research and clinical trials
Dr. Leng is a principal investigator on several cell-therapy clinical trials. The objective is to restore vision in GA patients, as current FDA-approved complement inhibitors can only slow the progression of the disease. Early phase 1 data across various trials have shown a positive "class effect," with patients demonstrating improved vision.
Dr. Leng’s research on cell-based therapies:
- RPE stem cells: These cells are transplanted subretinally with the intent that they will interdigitate with existing photoreceptors and take over RPE functions. They may also secrete local cytokines and growth factors to support native cells.
- Neural stem cells: Dr. Leng is also working on a CIRM-funded project at Stanford involving neural stem cells. Rather than becoming RPE, these cells act as a trophic factor (similar to CNTF), secreting growth factors that rejuvenate the surrounding tissue when injected under the retina.
Future outlook
Many companies are moving directly from phase 1/2 safety and dose-finding studies into pivotal trials. Results from these larger studies are expected soon.
