Future File is a Retinal Physician column designed to highlight new and innovative early-stage and preclinical concepts that could one day help to advance the everyday practice of retina specialists.
Photoreceptor Transplantation Still a Work in Progress
■ In a recent issue of Progress in Retinal and Eye Research, researchers from the Center for Regenerative Therapies in Dresden, Germany, reviewed the state of efforts to combat degenerative retinal diseases through photoreceptor transplantation. The researchers reported that loss of light-sensing photoreceptors due to retinal degeneration is, thus far, irreversible, but photoreceptor transplantation represents a potential therapeutic approach for such diseases. The study noted that retinal organoids are a potentially unlimited source of donor photoreceptors, while cytoplasmic material transfer must be considered in further studies of visual function recovery by cell transplantation. The researchers concluded that immune reaction to the graft needs to be properly understood prior to clinical translation.
Suprachoroidal Route for Gene Transfer
■ The 2 companies currently conducting clinical trials for continuous gene-derived anti-VEGF expression are using different routes to administer the genetically coded material. Regenxbio uses subretinal administration, while Adverum employs an intravitreal injection. Now, Clearside Biomedical in preclinical testing is demonstrating the potential advantages of suprachoroidal administration. At the recent Association for Research in Vision and Ophthalmology (ARVO) meeting, multiple posters were presented utilizing a suprachoroidal approach to deliver gene therapies in nonclinical models. Overall, the data presented suggest that suprachoroidal administration has the potential to offer targeted delivery of gene therapies without risks of vitrectomy and subretinal surgery. Clearside said it looks to optimize the procedure for gene therapy delivery using its proprietary suprachoroidal (SCS) injection platform in this setting.
At ARVO, Glenn Chung-Wing Yiu, MD, PhD, Assistant Professor of Ophthalmology, UC Davis, presented a poster on SCS injection of AAV8 for ocular gene delivery in a nonhuman primate. Although the sample size of eyes undergoing SCS injection of AAV8 expressing green fluorescent protein was small, Dr. Yiu concluded that SCS injection of AAV8 may be a feasible mode of ocular gene delivery with transduction of mostly retinal pigment epithelium rather than photoreceptors and in peripheral rather than macular regions. In the studies, maximal expression was seen at 1 month, and researchers noted that additional studies are recommended to optimize the extent and duration of viral transduction.
Another ARVO study of suprachoroidal administration for gene transfer, this one by researchers from Johns Hopkins University, found that suprachoroidal administration has the potential to deliver results similar to subretinal administration.
New Sustained-Release Implant Has Promise
■ A multidisciplinary team at Ohio State University has developed an injectable, biodegradable, bilayered (IBB) capsule that has proven in preclinical testing that it is effective in delivering anti-VEGF drugs into the eye continuously for 6 to 12 months. The researchers, who presented their findings at the recent ARVO meeting, said the novel IBB capsule showed no cytotoxicity, demonstrated excellent injectability, and maintained the high potency of anti-VEGF during long-term release. By meeting the needs of high drug payload and long-term sustainable release, the device may represent a promising evolution in the treatment of AMD as well as other ocular diseases and injuries.
Long-Acting Steroid Implant Combats Melanoma-Associated Retinopathy
■ In a groundbreaking effort, researchers from the University of Surrey and Royal Surrey County Hospital in the United Kingdom, supported by the electrophysiology department of Moorfields Eye Hospital, initiated a new approach in treating melanoma-associated retinopathy (MAR), a rare autoimmune syndrome occurring in patients with cancer, which can cause night blindness and progressive vision loss.
Working with a 73-year-old patient with MAR, researchers injected long-acting steroid implants into the eye. The implants slowly release fluocinolone acetonide, which prevent antiretinal antibodies attacking proteins in the organ. Current therapies to treat patients with MAR are limited in their effectiveness and may be harmful to some.
After 1 week of treatment, improvements in vision were detected, and detailed examination of the patient’s eye revealed that abnormalities previously observed, such as reduced electroretinogram recordings, had partly resolved, which is consistent with improved inner retinal cell function. Monitoring the patient over a 3-year period, researchers found that vision remained stable with visual acuity remaining at 20/20.
Simon Taylor, professor of ophthalmology at the University of Surrey, said in a news release, “To our knowledge, this is the first time the vision of a patient with melanoma-associated retinopathy has been treated and significantly improved with long-acting steroid implants. This offers a possible alternative option to patients, whose quality of life is significantly reduced.” RP