The Transplantation of Human Eye Allografts (THEA) program is on the cusp of making whole functional eye transplantation to restore vision for the blind and visually impaired a reality in our lifetime. Last month, the Advanced Research Projects Agency for Health (ARPA-H), an agency within the U.S. Department of Health and Human Services, announced that the THEA program intends to transplant whole human eyes to restore vision.

According to ARPA-H, “Vision loss affects over 7 million Americans, with the most common causes being age-related macular degeneration, glaucoma and diabetic retinopathy. Trauma and some hereditary conditions may also lead to blindness. While there are therapies to slow the progression of vision loss, there are currently none that restore sight.”

In short, the THEA program aims to transplant human eyes and reestablish visual connection to the brain.

    
  “Doctors have dreamed of transplanting whole human eyes to restore vision for centuries. With the recent foundational science developed as part of the National Eye Institute’s regenerative medicine initiative, now is the time to make whole eye transplantation a reality.”

 
  – Dr. Calvin Roberts, program manager for THEA  
  
 
    
Over 70,000 people in the U.S. donate their eyes after death each year. Yet only parts of the eye, most commonly the front surface or cornea, are currently able to be used for transplantation. As a result, the millions of people blinded by conditions of their retina and optic nerve have no options for improvement. THEA aims to address this issue, as it would transplant the whole donor eye and reconnect the nerves, muscles and blood vessels to the brain so that the eye can function for sight.

Dr. Calvin W. Roberts, president and chief executive officer of Lighthouse Guild, has taken on an additional role as program manager of ARPA-H’s transplantation program. Dr. Roberts is a renowned ophthalmic surgeon who specializes in laser and transplant eye surgeries. He has led the development of various pharmaceuticals, devices and diagnostic equipment for ophthalmology, and hosts the podcast series “On Tech and Vision”—where innovators discuss how rapidly evolving assistive technology creates equity among those who are visually impaired.

VMAIL Weekend reached out to Dr. Roberts to get his thoughts about how the THEA program will work.

“With THEA, we aim to revolutionize the reconnection of nerves to the brain and make these advancements accessible in the United States and around the globe, with the ambition to offer an alternative to lifelong blindness.”

“Doctors have dreamed of transplanting whole human eyes to restore vision for centuries. With the recent foundational science developed as part of the National Eye Institute’s regenerative medicine initiative, now is the time to make whole eye transplantation a reality,” Dr. Roberts said.

 
Calvin W. Roberts, MD.
Photo courtesy of ARPA-H/Adam Lee
 
“THEA has an ambitious goal and there is significant work to be done to make this a reality. First, we must find a way to preserve the eye and keep it viable from the time it leaves the donor to the time that it's implanted into the recipient.

“Second, which is critical, is the ability to reconnect the eye so that the eye is functioning and allows the person to see. And that's where the great science comes in as to how you would reconnect two ends of an optic nerve so that it functions and transmits the signal to the brain.

“The third part is the actual surgery itself. How are we going to do this surgery? Are we just going to transplant the eye? Are we going to transplant some other tissues near it? Depending upon what the clinical situation is, we need to figure out how we're going to accomplish the surgery, evaluate the patient and prevent rejection,” Dr. Roberts said.

To accomplish eye transplant surgery and healing, THEA will leverage emerging microsurgical techniques, coupled with genetic and cell-based therapies, to preserve or regrow nerves from the eye to the brain. These regenerative solutions could help prevent degenerative blindness and are a critical step toward successful whole eye transplantation to restore vision.

ARPA-H is emphasizing collaboration across academia and industry to accelerate these discoveries with unique tools not yet applied to ocular surgery.

“While it has been nearly 60 years since the first successful human heart transplant, we have not been able to use similar approaches to restore a person’s sight, and that’s what makes this an ARPA-hard problem to solve,” said ARPA-H director Renee Wegrzyn, Ph.D. “Through THEA, we’re seeking to develop the next breakthroughs in transplantation, preservation and neuroscience to address the challenge: ‘What if we could restore vision to those who are blind?’”

THEA intends to test and evaluate the best therapies to repair damaged nerves, to maintain critical structures in the eye, such as the retina and optic nerve viable after damage, and to prevent postoperative inflammation or rejection. Through a forthcoming Innovative Solutions Opening, (ISO) THEA will request proposals focused on three technical areas: retrieval of donor eyes and maintenance of the health of donor eyes until transplantation; optic nerve repair and regeneration; and surgical procedures, post-operative care and functional assessment.

 
 
Dr. Roberts said that each of the three technical areas “come with their own challenges and are hurdles THEA is aiming to overcome to develop the next breakthroughs in transplantation, preservation and neuroscience. To reach transformative health solutions for everyone, we need to push ourselves to think beyond our current limitations.

“The draft ISO includes detailed information on each technical area (TA) and metrics performers must meet, which will increase in difficulty and complexity over the course of the program. Performers will have the option of submitting proposals that address all TAs (TA1 – 3) or TA1 or TA2 only,” he said.

“An ISO is a funding opportunity solicitation with detailed information about the program. We anticipate posting the Innovation Solutions Opening in the next couple of weeks, though the draft ISO is available on SAM.gov now," Dr. Roberts said.

ARPA-H anticipates that teaming will be necessary to achieve the goals of THEA. And what will these teams of scientists, doctors and researchers look like? Dr. Roberts explained, “While not required, prospective performers across academia, clinical and industry are encouraged to form teams with varied technical expertise to accelerate these discoveries with unique tools not yet applied to ocular surgery. I encourage all interested research teams to register for THEA’s upcoming Proposers’ Day, being held in New York City and virtually on Feb. 15, 2024.”

Multiple awards under this solicitation are anticipated. Resources available will depend on the quality of the proposals received and the availability of funds. Learn more about THEA on its program page, including information about the Special Notice, Proposers’ Day registration and how to state interest to form an applicant team here.

The success of the program extends far beyond eye transplants and vision restoration. Techniques in microsurgery and gene or cell-based therapies for nerve regeneration may have the potential to be applied to other types of nervous system damage, including spinal cord injury. By starting with the eye’s nerves, the outputs of THEA could improve research into brain repair as well, according to ARPA-H.