PMID- 38160882
OWN - NLM
STAT- Publisher
LR  - 20240219
IS  - 1549-4713 (Electronic)
IS  - 0161-6420 (Linking)
DP  - 2023 Dec 30
TI  - Long-term Follow-up of a Phase 1/2a Clinical Trial of a Stem Cell-Derived 
      Bioengineered Retinal Pigment Epithelium Implant for Geographic Atrophy.
LID - S0161-6420(23)00935-1 [pii]
LID - 10.1016/j.ophtha.2023.12.028 [doi]
AB  - PURPOSE: To report long-term results from a phase 1/2a clinical trial assessment 
      of a scaffold-based human embryonic stem cell-derived retinal pigmented 
      epithelium (RPE) implant in patients with advanced geographic atrophy (GA). 
      DESIGN: A single-arm, open-label phase 1/2a clinical trial approved by the United 
      States Food and Drug Administration. PARTICIPANTS: Patients were 69-85 years of 
      age at the time of enrollment and were legally blind in the treated eye 
      (best-corrected visual acuity [BCVA], </= 20/200) as a result of GA involving the 
      fovea. METHODS: The clinical trial enrolled 16 patients, 15 of whom underwent 
      implantation successfully. The implant was administered to the worse-seeing eye 
      with the use of a custom subretinal insertion device. The companion nonimplanted 
      eye served as the control. The primary endpoint was at 1 year; thereafter, 
      patients were followed up at least yearly. MAIN OUTCOME MEASURES: Safety was the 
      primary endpoint of the study. The occurrence and frequency of adverse events 
      (AEs) were determined by scheduled eye examinations, including measurement of 
      BCVA and intraocular pressure and multimodal imaging. Serum antibody titers were 
      collected to monitor systemic humoral immune responses to the implanted cells. 
      RESULTS: At a median follow-up of 3 years, fundus photography revealed no 
      migration of the implant. No unanticipated, severe, implant-related AEs occurred, 
      and the most common anticipated severe AE (severe retinal hemorrhage) was 
      eliminated in the second cohort (9 patients) through improved intraoperative 
      hemostasis. Nonsevere, transient retinal hemorrhages were noted either during or 
      after surgery in all patients as anticipated for a subretinal surgical procedure. 
      Throughout the median 3-year follow-up, results show that implanted eyes were 
      more likely to improve by > 5 letters of BCVA and were less likely to worsen by > 
      5 letters compared with nonimplanted eyes. CONCLUSIONS: This report details the 
      long-term follow-up of patients with GA to receive a scaffold-based stem 
      cell-derived bioengineered RPE implant. Results show that the implant, at a 
      median 3-year follow-up, is safe and well tolerated in patients with advanced dry 
      age-related macular degeneration. The safety profile, along with the early 
      indication of efficacy, warrants further clinical evaluation of this novel 
      approach for the treatment of GA. FINANCIAL DISCLOSURE(S): Proprietary or 
      commercial disclosure may be found in the Footnotes and Disclosures at the end of 
      this article.
CI  - Copyright (c) 2024 American Academy of Ophthalmology. Published by Elsevier Inc. 
      All rights reserved.
FAU - Humayun, Mark S
AU  - Humayun MS
AD  - USC Roski Eye Institute, USC Ginsburg Institute for Biomedical Therapeutics and 
      Department of Ophthalmology, Keck School of Medicine, University of Southern 
      California, Los Angeles, California; Department of Biomedical Engineering, 
      University of Southern California, Los Angeles, California. Electronic address: 
      humayun@usc.edu.
FAU - Clegg, Dennis O
AU  - Clegg DO
AD  - Center for Stem Cell Biology and Engineering, Neuroscience Research Institute, 
      University of California, Santa Barbara, Santa Barbara, California.
FAU - Dayan, Margot S
AU  - Dayan MS
AD  - USC Roski Eye Institute, USC Ginsburg Institute for Biomedical Therapeutics and 
      Department of Ophthalmology, Keck School of Medicine, University of Southern 
      California, Los Angeles, California.
FAU - Kashani, Amir H
AU  - Kashani AH
AD  - Wilmer Eye Institute, Johns Hopkins School of Medicine, Johns Hopkins University, 
      Baltimore, Maryland.
FAU - Rahhal, Firas M
AU  - Rahhal FM
AD  - Retina-Vitreous Associates Medical Group, Beverly Hills, California.
FAU - Avery, Robert L
AU  - Avery RL
AD  - California Retina Consultants, Santa Barbara, California.
FAU - Salehi-Had, Hani
AU  - Salehi-Had H
AD  - Retina Associates of Southern California, Huntington Beach, California.
FAU - Chen, Sanford
AU  - Chen S
AD  - Orange County Retina Medical Group, Santa Ana, California.
FAU - Chan, Clement
AU  - Chan C
AD  - Southern California Desert Retina Consultants, Palm Desert, California.
FAU - Palejwala, Neal
AU  - Palejwala N
AD  - Retinal Consultants of Arizona, Retinal Research Institute LLC, Phoenix, Arizona.
FAU - Ingram, April
AU  - Ingram A
AD  - Regenerative Patch Technologies, Menlo Park, California.
FAU - Mitra, Debbie
AU  - Mitra D
AD  - USC Roski Eye Institute, USC Ginsburg Institute for Biomedical Therapeutics and 
      Department of Ophthalmology, Keck School of Medicine, University of Southern 
      California, Los Angeles, California.
FAU - Pennington, Britney O
AU  - Pennington BO
AD  - Center for Stem Cell Biology and Engineering, Neuroscience Research Institute, 
      University of California, Santa Barbara, Santa Barbara, California; Regenerative 
      Patch Technologies, Menlo Park, California.
FAU - Hinman, Cassidy
AU  - Hinman C
AD  - Center for Stem Cell Biology and Engineering, Neuroscience Research Institute, 
      University of California, Santa Barbara, Santa Barbara, California; Regenerative 
      Patch Technologies, Menlo Park, California.
FAU - Faynus, Mohamed A
AU  - Faynus MA
AD  - Center for Stem Cell Biology and Engineering, Neuroscience Research Institute, 
      University of California, Santa Barbara, Santa Barbara, California; Regenerative 
      Patch Technologies, Menlo Park, California.
FAU - Bailey, Jeffrey K
AU  - Bailey JK
AD  - Center for Stem Cell Biology and Engineering, Neuroscience Research Institute, 
      University of California, Santa Barbara, Santa Barbara, California; Regenerative 
      Patch Technologies, Menlo Park, California.
FAU - Johnson, Lincoln V
AU  - Johnson LV
AD  - Regenerative Patch Technologies, Menlo Park, California.
FAU - Lebkowski, Jane S
AU  - Lebkowski JS
AD  - Regenerative Patch Technologies, Menlo Park, California.
LA  - eng
PT  - Journal Article
DEP - 20231230
PL  - United States
TA  - Ophthalmology
JT  - Ophthalmology
JID - 7802443
SB  - IM
OTO - NOTNLM
OT  - Clinical trial
OT  - Geographic atrophy
OT  - Implant
OT  - RPE
OT  - Stem cells
EDAT- 2024/01/02 11:42
MHDA- 2024/01/02 11:42
CRDT- 2023/12/31 19:16
PHST- 2023/04/18 00:00 [received]
PHST- 2023/06/03 00:00 [revised]
PHST- 2023/06/03 00:00 [accepted]
PHST- 2024/01/02 11:42 [pubmed]
PHST- 2024/01/02 11:42 [medline]
PHST- 2023/12/31 19:16 [entrez]
AID - S0161-6420(23)00935-1 [pii]
AID - 10.1016/j.ophtha.2023.12.028 [doi]
PST - aheadofprint
SO  - Ophthalmology. 2023 Dec 30:S0161-6420(23)00935-1. doi: 
      10.1016/j.ophtha.2023.12.028.