A recent study demonstrated that surgical removal of choroidal neovascularization prior to human embryonic stem cell-derived retinal pigment epithelium cell transplantation may improve safety and effectiveness, but intraoperative bleeding and incomplete choroidal neovascularization removal increase the risk of inflammation and choroidal neovascularization recurrence.
Researchers at Southwest Eye Hospital in China conducted a phase I, open-label clinical trial involving 10 patients (6 males, 4 females, aged 48 to 71 years) with wet age-related macular degeneration (AMD). The patients underwent peripheral retinal detachment and choroidal neovascularization (CNV) removal, followed by subretinal transplantation of human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE) cells. Seven of the patients had successful CNV removal without bleeding (group 1), while 3 of the patients had CNV removal complicated by intraoperative bleeding (group 2), the investigators reported in a study published in Stem Cell Reports.
Patients were monitored for 12 months using best-corrected visual acuity (BCVA), optical coherence tomography (OCT), fundus fluorescein angiography (FFA), and optical coherence tomography angiography (OCTA).
No severe complications (endophthalmitis, retinal detachment, or secondary glaucoma) were reported. CNV recurrence occurred in 1 patient from group 2 at 9 months. This finding was confirmed by OCTA, and the patient required additional antivascular endothelial growth factor therapy. Persistent fundus inflammation was observed in patients with intraoperative bleeding. Group 2 patients also developed more postoperative complications compared with group 1 patients, including macular edema (n = 3/3) and epiretinal membrane formation (n = 3/3).
The researchers noted that 6 of the 10 patients had BCVA improvements of more than 10 ETDRS letters, and 3 patients improved by more than 20 letters at 12 months. Patients in group 1 had better visual outcomes, with an average 12-letter gain compared with a three-letter gain in group 2.
Group 1 patients also showed stable integration of transplanted RPE cells with no recurrent CNV or inflammation. Group 2 patients had persistent macular edema, likely caused by blood-retinal barrier disruption and inflammation.
Study limitations included its small sample size, which limited its statistical power. Patients also required 4 months of immunosuppressive therapy postoperatively to prevent rejection, and long-term follow-up beyond 12 months is needed to assess durability of outcomes.
“CNV removal creates a more stable microenvironment for the survival and integration of the transplanted RPE cells,” lead study author Ying Xue Lv wrote with colleagues. “Close adhesion of the CNV to the underlying tissue, as detected using OCT preoperatively, is a significant surgical risk factor. Patients with close CNV adhesions should be carefully evaluated, and alternative treatments may be more appropriate in such cases,” they emphasized.
The factors that contributed “to unsatisfactory outcomes and [the researchers’] experiences managing complications in this study … could help inform the preoperative screening of participants and postoperative management in future studies,” the study authors concluded.
No conflicts of interest were disclosed.