A groundbreaking advancement in assistive technology has emerged from Stanford Medicine, offering a profound impact on the lives of individuals battling advanced age-related macular degeneration. A minuscule, wireless retinal implant, known as PRIMA, when paired with sophisticated smart glasses, has demonstrated a remarkable ability to partially restore vision. In a pivotal clinical study, a collaborative effort led by Stanford Medicine and international partners, a significant majority of participants—27 out of 32—regained the ability to read within a year of receiving the implant, marking a monumental leap in the restoration of functional vision. This innovative system not only allows patients to perceive shapes and patterns, achieving what is termed "form vision," but also enhances their overall visual acuity to levels comparable to 20/42 with the aid of digital features like adjustable zoom and contrast enhancement. The groundbreaking findings, published on October 20th in the prestigious New England Journal of Medicine, represent a watershed moment in the quest to combat irreversible blindness.

The PRIMA implant stands as the first prosthetic eye device capable of restoring usable vision to individuals whose sight loss was previously considered untreatable. This pioneering technology bypasses the damaged photoreceptor cells in the retina, directly stimulating the remaining retinal neurons to send visual signals to the brain. "All previous attempts to provide vision with prosthetic devices resulted in basically light sensitivity, not really form vision," stated Daniel Palanker, PhD, a professor of ophthalmology and a co-senior author of the paper. "We are the first to provide form vision." The research was spearheaded by a multidisciplinary team, co-led by José-Alain Sahel, MD, a professor of ophthalmology at the University of Pittsburgh School of Medicine, with Frank Holz, MD, of the University of Bonn in Germany, serving as the lead author. This collaborative spirit underscores the global effort behind this transformative technology.

The intricate workings of the PRIMA system are a testament to decades of dedicated scientific pursuit. It comprises two essential components: a compact camera integrated into a pair of advanced smart glasses, and the wireless chip implanted within the retina. The camera captures the visual world and transmits this information via infrared light to the retinal implant. Upon receiving the infrared signal, the chip converts it into electrical impulses. These electrical signals effectively act as a substitute for the malfunctioning photoreceptor cells, which are naturally responsible for detecting light and relaying visual data to the brain. This elegant solution bypasses the diseased cells and leverages the intact neural pathways that remain.

The genesis of the PRIMA project can be traced back two decades to Professor Palanker’s work with ophthalmic lasers for treating eye conditions. "I realized we should use the fact that the eye is transparent and deliver information by light," he recounted. This early conceptualization, a bold vision in 2005, has now materialized into a device that is "remarkably well" functioning in patients. The journey from concept to clinical success involved numerous prototypes, extensive animal testing, and a crucial initial human trial, highlighting the perseverance and meticulous development process.

The success of the PRIMA system is particularly significant for individuals suffering from advanced age-related macular degeneration, specifically geographic atrophy. This condition, characterized by the progressive deterioration of central vision, affects over five million people globally and is the primary cause of irreversible blindness in older adults. In macular degeneration, the crucial light-sensitive photoreceptor cells in the central retina are destroyed, leaving patients with only limited peripheral vision. However, a critical observation that fuels the PRIMA technology is that many of the retinal neurons responsible for processing visual information often remain intact. PRIMA ingeniously capitalizes on these surviving neural structures.

The implant itself is remarkably small, measuring just 2 by 2 millimeters, and is strategically placed in the retinal region where photoreceptor loss has occurred. A key innovation lies in its responsiveness to infrared light, emitted from the glasses, rather than visible light, which is how natural photoreceptors function. "The projection is done by infrared because we want to make sure it’s invisible to the remaining photoreceptors outside the implant," explained Palanker. This selective stimulation ensures that the prosthetic vision does not interfere with any remaining natural peripheral vision.

A crucial benefit of this design is the ability for patients to simultaneously utilize their natural peripheral vision and the newly restored central prosthetic vision. This synergistic integration significantly enhances their spatial awareness, orientation, and overall mobility. "The fact that they see simultaneously prosthetic and peripheral vision is important because they can merge and use vision to its fullest," Palanker emphasized. Furthermore, the PRIMA implant is photovoltaic, meaning it generates its own electrical current solely from light. This self-sustaining power source eliminates the need for external power supplies and cumbersome cables that would typically extend outside the eye, a significant improvement over earlier generations of artificial eye devices. This wireless, self-contained nature makes the implant safer and more practical for long-term use.

The clinical trial involved 38 participants, all over the age of 60, who had geographic atrophy due to age-related macular degeneration and a visual acuity worse than 20/320 in at least one eye. Following the implantation of the chip in one eye, patients commenced using the smart glasses four to five weeks later. While some individuals could discern patterns immediately, all participants experienced significant improvements in their visual acuity over several months of dedicated training. "It may take several months of training to reach top performance — which is similar to what cochlear implants require to master prosthetic hearing," Palanker noted, drawing a parallel to other complex sensory restoration technologies.

Of the 32 patients who successfully completed the one-year trial, an impressive 27 were able to read. Moreover, 26 participants demonstrated clinically meaningful improvements in their visual acuity, defined as the ability to read at least two additional lines on a standard eye chart. On average, participants experienced a five-line improvement in visual acuity, with one individual showing a remarkable twelve-line improvement. The prosthesis proved instrumental in their daily lives, enabling them to read books, decipher food labels, and navigate public transportation by reading subway signs. The smart glasses offered crucial functionalities, allowing users to adjust contrast and brightness, and magnify their view up to twelve times. User satisfaction was also high, with two-thirds of participants reporting medium to high levels of satisfaction with the device. While 19 participants experienced side effects, including ocular hypertension, retinal tears, and subretinal hemorrhage, none were life-threatening, and nearly all resolved within two months, underscoring the generally safe profile of the implant.

Looking towards the future, the PRIMA device, currently providing black-and-white vision, is poised for further enhancement. Palanker is actively developing software to introduce a full range of grayscale, a feature highly desired by patients for tasks such as face recognition. "Number one on the patients’ wish list is reading, but number two, very close behind, is face recognition," he stated. "And face recognition requires grayscale."

Beyond grayscale, Palanker is also engineering chips with significantly higher resolution. The current resolution is limited by the pixel size of 100 microns, with 378 pixels per chip. The next generation, already tested in rats, aims to incorporate pixels as small as 20 microns, potentially increasing the pixel count to 10,000 per chip. This advancement could provide patients with 20/80 vision, and with electronic zoom capabilities, approach 20/20 vision. Researchers are also eager to explore the applicability of the PRIMA device for other forms of blindness caused by photoreceptor loss. "This is the first version of the chip, and resolution is relatively low," Palanker acknowledged. "The next generation of the chip, with smaller pixels, will have better resolution and be paired with sleeker-looking glasses."

The collaborative nature of this research is evident in the extensive list of contributing institutions, including researchers from the University of Bonn, Germany; Hôpital Fondation A. de Rothschild, France; Moorfields Eye Hospital and University College London; Ludwigshafen Academic Teaching Hospital; University of Rome Tor Vergata; Medical Center Schleswig-Holstein, University of Lübeck; L’Hôpital Universitaire de la Croix-Rousse and Université Claude Bernard Lyon 1; Azienda Ospedaliera San Giovanni Addolorata; Centre Monticelli Paradis and L’Université d’Aix-Marseille; Intercommunal Hospital of Créteil and Henri Mondor Hospital; Knappschaft Hospital Saar; Nantes University; University Eye Hospital Tübingen; University of Münster Medical Center; Bordeaux University Hospital; Hôpital National des 15-20; Erasmus University Medical Center; University of Ulm; Science Corp.; University of California, San Francisco; University of Washington; University of Pittsburgh School of Medicine; and Sorbonne Université. This monumental undertaking was generously supported by funding from Science Corp., the National Institute for Health and Care Research, Moorfields Eye Hospital National Health Service Foundation Trust, and University College London Institute of Ophthalmology, underscoring the vital role of diverse funding streams in advancing cutting-edge medical technologies. The PRIMA system represents not just a technological marvel, but a beacon of hope, illuminating a path toward regaining sight for millions.