Vision researchers at the USC Roski Eye Institute play a critical role in driving fundamental and translational research to advance patient care by establishing relationships that foster innovation and result in new treatments. The USC Roski Eye Institute understands the profound impact research has in developing future treatments by supporting our vision science researchers.
Selected Highlights in Basic Science and Translational Research
Over the past several years, major advances have been made in the application of engineering to medical problems. This has led to the clinical testing and FDA approval of an electronic prosthetic device for sight restoration in severe cases of retinitis pigmentosa (RP). Through understanding retinal degenerative diseases, such as RP, our scientists, clinicians and engineers converged to develop the first FDA-approved retinal prosthesis, Argus II. Co-inventor, Mark Humayun, MD, PhD, through the culmination of 20 years of research, created a device that restores functional vision to those blinded by RP. This has been an outstanding partnership between USC and Second Sight Medical Products that has yielded many patents as well as a successful clinical trial.
To improve patient compliance, researchers at USC Roski Eye Institute developed a “smart” device to control medical dosing. A tiny, implantable pump delivers precise amounts of medication as required at proper intervals directly into the eye. It is refillable, and is programmed and recharged wirelessly.
Originally developed for treating glaucoma, the second-generation micropump system is designed for retinal disease. It is smaller, has a greater reservoir volume and offers the possibility of multiple chambers for more than one medication. For retinal patients, localized delivery of medications into the eye has the advantage of eliminating possible systemic side effects.
In 2014, USC Roski Eye Institute physicians performed noninvasive surgery for the first-in-man implant of the novel ophthalmic medication-delivery system in patients with diabetic macular edema. The clinical trial is to verify the device’s feasibility for controlled drug delivery for chronic diseases of the retina. Further investigations will evaluate its effectiveness and be used to fine-tune its operation.
The micropump is practical and convenient to use. The medication reservoir can be refilled with up to 100 microliters within two minutes via a thin 31-gauge needle. It stores up to 12 months of medication before requiring a refill. The device has been shown to function effectively for up to seven years.
This second-generation micropump holds the promise of delivering microdoses of medication to an exact schedule so patients with diabetic macular edema experience optimal outcomes from therapy — without being concerned about putting drops in their eyes.
The World Health Organization estimates that only half of patients in developed countries follow treatment recommendations. This tiny pump has the potential for a huge impact.
The Institute’s emphasis on translational research has also resulted in the development of, arguably one of the most groundbreaking ophthalmic inventions to date, optical coherence tomography. This technology is an essential imaging diagnostic tool used worldwide and revolutionized how ophthalmologists diagnose diseases of the eye.
Further, this translational research extends to development of hyperspectral imaging techniques, where unprecedented spectroscopic images of certain structures of the eye, like the retina, can be captured. Hyperspectral imaging is a method of simultaneously recording multiple wavelengths at each pixel of a conventional fundus image (images of the interior of the eye) within the time span of a standard flash photograph. Unlike conventional imaging methods, hyperspectral imaging does not require scanning, image registration or use of filters. In addition, hyperspectral imagers can be used to study the quantity and variation in any tissue with unique spectral features (e.g. hemoglobin, melanin, drusen etc).
Human Connectome Project
Distinguished ophthalmology faculty members, Dr. Arthur Toga and Dr. Paul Thompson have been at the leading edge of the complex frontier of brain imaging for over two decades. The recruitment of these eminent neuroscientists, along with their talented team of over 140 members has championed the development of the USC Mark and Mary Stevens Center for Neuroimaging and Informatics, catapulting USC to a position among the leading neuroscience research institutions in the world. Many of the team’s leading researchers are cross-appointed to the USC Roski Eye Institute, allowing for meaningful collaborations that will directly impact our patients’ lives, unparalleled educational and research opportunities for students, residents, and faculty, as well as advancing our understanding of the visual pathways. The Human Connectome Project is finding answers to fundamental questions in the relationship between eye disease and its relationship to the central visual processing. More specifically, Drs. Toga and Thompson are attempting to answer questions such as:
- How does the precise topography of eye disease map onto changes in brain?
- Is acquired retinal and optic nerve damage in diseases such as glaucoma, macular degeneration related to local effects upon the structure and function of central pathways?
- Are any of these effects of vision loss on central pathways reversible?
The USC Roski Eye Institute has received a new grant to investigate the relationship between Human Connectomes (brain mapping) and eye diseases to create the next generation of sight restoration therapies. To learn more please visit: http://ini.usc.edu/
The USC Roski Eye Institute clinicians are making great strides in protecting patient’s vision through conducting translational research in the epidemiology of eye disease. Rohit Varma, MD, MPH, professor and chair of the Department of Ophthalmology, director of the USC Roski Eye Institute, established the USC Roski Eye Institute Ocular Epidemiology Center, and has devoted his career to conducting community health-based studies that have changed our approach to diagnosis and treatment of eye diseases. The USC Ocular Epidemiology Center’s mission is to better understand the underlying pathologies and risk factors associated with different eye conditions and eye diseases (such as visual impairment and blindness, lens opacities, age-related macular degeneration (AMD), diabetic retinopathy and glaucoma) among different racial/ethnic aging populations. The potential to dramatically reduce the personal and socioeconomic burden of vision loss is possible, as these studies have led to early diagnosis and prevention of eye disease. Dr. Varma’s longitudinal studies are the largest in the world and have focused on children and adults. He is the principal investigator of 3 large NIH/National Eye Institute (NEI) -funded studies of eye disease in ethnic populations: Los Angeles Latino Eye Study (LALES), the Chinese American Eye Study (CHES) and the African American Eye Study (AFEDS). Dr. Varma was also the PI for the NIH/NEI funded Multi-Ethnic Pediatric Eye Diseases Study (MEPEDS). These studies have provided insights into improved strategies for public health interventions, and as a result, have had direct impact on health care policy in America. Read more about the study at www.thehealthyeye.org/.
Researchers at the USC Roski Eye Institute are working to restore vision to patients with advanced age related macular degeneration (AMD). The California Institute for Regenerative Medicine (CIRM) has awarded USC researchers Mark Humayun, MD, PhD, and David Hinton, MD, a $19 million grant to develop and perform a human clinical trial of a novel treatment for advanced, dry AMD. By growing thin sheets of stem cell-derived cells and surgically implanting them into the eye, our researchers hope to restore the retina’s critical light sensitive cells to replace the diseased tissue.
USC stem cell researchers identified a stem cell line that contains the characteristics of normal adult retinal pigment epithelium (RPE) cells. USC bioengineers developed a material that can act as a scaffold for RPE cells to allow them to function normally. Their collaborative advancements will be at the center of Phase I clinical trials expected to begin within one year.
Retinal-cell implants have the potential to improve the lives of an estimated 1.75 million people in the United States who have AMD — the leading cause of vision loss and blindness among the elderly.
Our clinician-scientists conduct clinical trials and train the next generation of ophthalmologists where patient-centered collaboration improves vision and fuels the development of new therapies. Please click here for a comprehensive list of our ongoing and completed clinical trials. From studying new experimental drugs to FDA approved devices, our clinicians are at the forefront of clinical research as they continue to enhance the level of care of each patient they see.
Reinventing Glaucoma Treatment
Despite their proven effectiveness, trabeculectomies and tube shunts are highly invasive and have a one year complication rate as high as 50 percent for high-risk glaucoma patients. Outcomes also have shown a high degree of variability that can lead to too little or too much IOP reduction. Over time, shunts can become less effective and require replacement.
Researchers at USC Roski Eye Institute have developed a more effective alternative — a soft stent made of permanent, collagen-derived gelatin.
Approximately the width of a human hair, the stent is injected into the eye through a small, self-sealing corneal incision. It creates a gentle outflow of fluid from the eye’s anterior chamber into the surrounding subconjuctival tissue. This pathway for drainage has been proven effective and is preferred by physicians worldwide.
The gel stent is pliable, noninflammatory and conforms to eye tissue, which is likely to minimize issues with migration, erosion and corneal endothelial damage often seen with synthetic materials. The preloaded injector enables standardized minimally invasive insertion of the stent. International clinical trials have shown that the gel stent significantly and safely lowers intraocular pressure.
The gel stent is approved in Europe for primary open angle glaucoma where other treatment methods have failed. In the United States, it is an investigational device, awaiting approval by the U.S. Food and Drug Administration.
This breakthrough holds the promise to prevent glaucoma-related vision loss through a broadly adoptable 10-minute procedure. Glaucoma is the world’s No. 2 cause of blindness and affects more than 60 million people worldwide.
Identifying the Cause of Retinoblastoma
USC Roski Eye Institute faculty researcher David E. Cobrinik, MD, PhD, and his colleagues made a major breakthrough in 2014 by identifying the type of cell and signaling pathways that lead to the development of retinoblastoma.
Cobrinik’s research discovered that retinoblastomas originate in immature cone photoreceptor cells that have not fully differentiated. When the RB1 gene in those cells mutates, it no longer encodes a tumor suppressor protein (Rb) that prevents excessive cell growth, resulting in the development of retinoblastoma tumors.
These findings significantly advance the understanding of cancer because they more generally imply that cancers can develop through the collaboration between a cancer-causing mutation — in this case, inactivation of the RB1 gene — and the circuitry of the cell of origin that sensitizes Rb protein loss.
Ultimately, Cobrinik and his research team aim to characterize the cell typespecific signaling pathways that collaborate with RB1 inactivation to identify therapeutic targets for retinoblastoma and other cancers.
Next, read about our clinical research.