A bioengineered monolayer of retinal pigment epithelium (RPE), lying atop a synthetic Bruch membrane, can be safely and accurately implanted beneath sections of retina that have been damaged by geographic atrophy.1
Researchers at the University of Southern California (USC) in Los Angeles hope this proof-of-principle clinical trial might be a step toward the first surgical treatment that could prevent, and perhaps reverse, the vision loss caused by the dry form of age-related macular degeneration (AMD), said researcher Mark S. Humayun, MD, PhD, at USC.
Study specifics. For this phase 1/2a safety study, lead coauthor Amir H. Kashani, MD, PhD—along with Dr. Humayun and the research team—implanted 3.5 × 6.25 mm sheets of parylene (a polymer) carrying polarized human embryonic stem cell–derived RPE into the eyes of 15 people with dry AMD.
In their report on the surgical, anatomic, and early safety outcomes of the procedure, the researchers noted the following:
- Using a special tool, the proprietary ultrathin carrier for the RPE cells could be folded and successfully inserted through an approximately 1-mm sclerotomy into a dissected retinal pocket, where the device remained stable perioperatively.
- The implantation failed in a 16th patient, apparently because of accumulated debris in the subretinal space during a long surgery.
- Intraoperative optical coherence tomography (iOCT) aided the surgeon in placing the device directly underneath the area of retinal damage, but iOCT was not necessary.
- The most common adverse events in the intra- and perioperative period were mild to moderate subretinal hemorrhages, which were asymptomatic.
- Surgical times ranged from 121-466 minutes (mean, 160 minutes), and they improved sufficiently with experience to suggest that the procedure could be performed on an outpatient basis.
Analysis of outcomes in the 15 patients after one year of follow-up is expected to be complete in time for presentation later this year at AAO 2020, Dr. Humayun said. An earlier report on the study’s first four successful implantations suggested that the replacement RPE might carry visual benefits,2 but data analysis needs to be completed on all implants for at least one year, he added.
Why an implant? This approach to ameliorating the vision loss of dry AMD differs in important ways from the approaches taken by others, Dr. Humayun said. For instance, why not inject RPE cells in suspension into these eyes? “Because other companies have looked at [injections] and determined that the cells don’t line up, they don’t line up right side up, and they tend to clump rather than form a polarized monolayer in the subretinal space where they are needed,” Dr. Humayun said. “We felt very strongly that we needed to implant these cells in the subretinal space on a scaffold.”
The parylene material of the scaffold had to be custom engineered to mimic Bruch membrane, to be permeable to molecules that RPE cells require to survive, he said. “It allows the exchange of nutrients across the membrane.”
Potential role. If intravitreal injections eventually gain approval for treatment of dry AMD, they might be used to prevent progression, Dr. Humayun said. “But if a patient has already progressed to a certain level of vision loss, or their disease is not really being slowed down, then you would need an implant to treat their condition.”
1 Kashani AH et al. Ophthalmol Retina. 2020;4(3):264-273.
2 Kashani AH et al. Sci Transl Med. 2018;10(435).
Relevant financial disclosures—Dr. Humayun: Regenerative Patch Technologies: C,O,P; USC: E,P.
For full disclosures and the disclosure key, see below.
Full Financial Disclosures
Dr. Chen Research related to this study was funded by a career development award from Research to Prevent Blindness and by the NEI.
Dr. Humayun Allergan: C,L; Duke Eye Center: P; Eyemedix: C,O,P,S; Iridex: P; Johns Hopkins University: P; Lutronic Vision: C,O; MTTR: C,O; Outlook Therapeutics: C; Regenerative Patch Technologies: C,O,P; Replenish: C,O,P; Santen: C,L; Second Sight Medical Products: O,P; USC: E,P.
Dr. Morley None.
Dr. Rose-Nussbaumer None.
||Consultant fee, paid advisory boards, or fees for attending a meeting.
||Employed by a commercial company.
||Lecture fees or honoraria, travel fees or reimbursements when speaking at the invitation of a commercial company.
||Equity ownership/stock options in publicly or privately traded firms, excluding mutual funds.
||Patents and/or royalties for intellectual property.
||Grant support or other financial support to the investigator from all sources, including research support from government agencies (e.g., NIH), foundations, device manufacturers, and/or pharmaceutical companies.
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