Inspiring Hope:

The Byers Eye Institute at Stanford is a place of many “firsts,” but the biggest one may be just on the horizon: vision-restoring whole eye transplants — a potential panacea to bring back vision for the blind. 

Stanford University has received an award to bring together more than 40 scientists, surgeons, and industry experts hand-picked from around the country to work on making whole eye transplants a reality. Jeffrey Goldberg, MD, PhD, Blumenkranz Smead professor and chair of ophthalmology at the Byers Eye Institute at Stanford, will serve as principal investigator. José-Alain Sahel, MD, professor and chair of the Department of Ophthalmology at the University of Pittsburgh, will co-direct the initiative with Goldberg.

The award of up to $56 million comes from the Advanced Research Projects Agency for Health (ARPA-H), a federal agency established within the U.S. Department of Health and Human Services. The agency called for proposals in 2024 for its Transplantation of Human Eye Allografts (THEA) program.

The awarded project led by Stanford is aptly called VISION, an acronym for Viability, Imaging, Surgical, Immunomodulation, Ocular preservation and Neuroregeneration (VISION) Strategies for Whole Eye Transplant — a reflection of the breadth of the collaboration assembled to solve such a complex challenge.

"Scientific breakthroughs are impossible without strong collaborations," Sahel said. "By combining the deep knowledge about ophthalmology, tissue preservation and regeneration, immunology, and surgery of world-class scientists at Byers Eye Institute, University of Pittsburgh, and consortium members from top institutions, we are well-positioned to set the foundational steps toward restoring vision using whole eye transplant."

Transplants aren’t new in ophthalmology. Annually, more than 70,000 people in the United States donate their eyes after they die, allowing for life-improving and vision-saving transplants of the cornea, the clear, outermost layer of the eye.

But those transplants don’t address the other most common causes of irreversible vision loss in the world, including glaucoma, macular degeneration, and diabetic retinopathy.

That’s where doctors hope the VISION project will come in. The biggest challenge the team will face is moving whole eye transplants from aesthetic to functional by figuring out how to regenerate the optic nerve, which connects the eye to the brain.

“This group of people have been working for decades now on figuring out how to promote optic nerve regeneration and retinal neuron survival in glaucoma and other blinding diseases” Goldberg said. “That positions us to be the best situated to take on optic nerve regeneration and neuronal cell survival in the context of eye transplant.”

The ‘whole’ plan

The THEA plan is holistic in every sense of the word.

The team is made up of a potent mix of expertise and skill, which will be needed as they simultaneously advance and create cutting-edge medical devices, artificial intelligence integrations, new surgical techniques, regenerative medicine breakthroughs and rejection rate mitigation strategies. The group will work dynamically, sharing information in real-time and pursuing the most promising leads.

Meticulous donor eye selection, advanced ocular imaging, and specialized logistics in organ procurement and preservation will also be critical for success. Collaborators on this team are already established leaders in these key areas of transplant science. In the end, tailored post-care rehabilitation for eye recipients will set patients on the right track.

Amid the technical details, equity and accessibility play a big role in the plan.

“Eye transplants stand to address the most severely blind, and because the risk of that severity of blindness goes up with decreasing access to medical care, the whole program stands to equalize access to care and access to vision,” said Wendy Liu, MD, PhD, professor of ophthalmology, one of eight Stanford faculty working on the project.

While whole eye transplants are the north star of the three-phase, six-year project, the effort will undoubtedly bring with it more breakthroughs along the way, and that is just as exciting, Goldberg said.

“As we develop a series of new technologies that could be vision restorative in THEA and also in the many patients with glaucoma and other eye diseases, we’ll leverage all the proper channels to ensure new drugs, gene therapies, and devices can be accessible to all,” he said.
 

The Byers Eye Institute team

In addition to Goldberg — an internationally recognized expert on glaucoma, regenerative medicine, neuroprotection, and developing new therapies — several of the Byers Eye Institute faculty research regenerative medicine and neuroprotection, including Yang Hu, MD, PhD, professor of ophthalmology who is also an expert in neuroprotection and optic nerve regeneration drug development.

Michael Kapiloff, MD, PhD, Reinhard Family Professor, delves into basic science and translational research around damage to the optic nerve and the retina that causes permanent vision loss, as in glaucoma and traumatic injuries. Liu studies cellular processes, including mechanosensation — how the brain interprets sensations — which contribute to the health of retinal ganglion cells and the optic nerve.

David Myung, MD, PhD, associate professor of ophthalmology has carved out an interdisciplinary research program focused on ophthalmic innovation, regenerative medicine through tissue engineering, and AI-enabled telemedicine. Novel nerve grafts and supportive wraps from his lab will facilitate optic nerve repair.

Other department THEA members bring with them deep knowledge on healing after an injury, surgery or disease. Benyam Kinde, MD, PhD, assistant professor of ophthalmology, studies damage responses in DNA after optic nerve injury, and brings expertise in oculoplastics and orbital surgery, the skills that will be critical to actual successful eye transplant.

Andrea Kossler, MD, FACS, associate professor of ophthalmology and director of oculofacial plastic and orbital surgery and the Thyroid Eye Disease Center at Stanford, is a leading expert in orbital surgery and innovation. She researches new treatments and novel surgeries, including neurotization, a technique to transplant healthy nerves into diseased eyes to help patients regain visual function.

Alfredo Dubra, PhD, professor of ophthalmology is a leader in advancing imaging technologies that improve how doctors understand, diagnose, and monitor vision-stealing conditions — technology that will now help pave a path toward whole eye transplants. 

“The progress that we make in studying cell survival, neuroprotection, and regeneration for eye transplant is almost certainly going to spin off technologies, therapies, and advances that could help many patients who have lost vision,” Kapiloff said. “These may be patients who don't need a whole eye transplant, they just need the regenerative therapy we’re working toward as part of this project.”

The THEA project is a milestone initiative, not just for the scientists involved and the patients who will hopefully one day regain their vision through an eye transplant, but for everyone working toward the Byers Eye Institute’s overarching mission to eradicate blindness.

“It’s a specific population of patients who will be appropriate for eye transplant — people who are blind in both eyes, for example,” Goldberg said. “Ultimately, this fits perfectly with our broader goals of restoring eyesight and eradicating blindness.”