Embryonic Stem Cells for AMD: A Promise Fulfilled?

Brianne N. Hobbs, OD


January 23, 2015

Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium in Patients With Age-Related Macular Degeneration and Stargardt's Macular Dystrophy: Follow-up of Two Open-Label Phase 1/2 Studies

Schwartz SD, Regillo CD, Lam BL, et al
Lancet. 2014 Oct 15. [Epub ahead of print]

Subretinal Transplantation Studies

The promise of embryonic stem cells (ESCs) seems limitless. From spinal cord injuries to diabetes to treatment of previously untreatable retinal diseases, ESCs seem to be the long-awaited answer to chronic degenerative conditions. The magic of ESCs lies in their pluripotency—the ability to differentiate into all cell types within the body.

Specific to the eye, ESCs may be useful in Stargardt macular dystrophy and nonexudative age-related macular degeneration (AMD), diseases characterized by dysfunctional retinal pigment epithelium (RPE). The RPE supports the viability of the adjacent photoreceptors, and it is possible that by transplanting RPE cells derived from ESCs, the photoreceptor degeneration could be halted.

ESCs are not without their concerns, however. A storm of controversy exists about the ethics of using cells that can only be obtained from embryos. There are also legitimate risks associated with ESCs, including teratoma formation and the possibility of ESCs differentiating into unwanted cell types. Immune rejection can also occur, but with the eye being largely immunoprivileged, it is an ideal place to explore the use of ESCs, and the chance of rejection is minimized.

Study Findings

Schwartz and colleagues investigated the use of ESCs in the treatment of AMD and Stargardt macular dystrophy. Eighteen eyes were included in the study: nine with AMD and nine with Stargardt macular dystrophy. To be included in the study, visual acuity had to be 20/200 or worse, and only one eye per patient could be enrolled.

Subretinal transplantation of ESCs was performed, and patients received one of three quantities of ESCs: 50,000 cells, 100,000 cells, or 150,000 cells. Patients received systemic immunosuppressive therapy to minimize transplant rejection and were followed for a median of 22 months.

Primary endpoints were safety and tolerability of the transplanted tissue. The secondary endpoint was efficacy and included such measures as visual acuity, visual field testing, electroretinography, quality-of-life surveys, and optical coherence tomography analysis.

Thirteen of the 18 patients developed areas of increased subretinal pigmentation, most commonly at the border of the atrophic area. Although the postoperative increase seems promising, there was no correlation between the increase in retinal pigment and visual improvement. Best-corrected visual acuity improved significantly in 10 patients, remained nearly the same in seven eyes, and worsened in one eye by 10 letters. The untreated eye of each patient had no improvement in acuity, providing evidence that the transplant was responsible for the improved acuity. Visual field, static perimetry, electroretinography, and reading speed were assessed, but there were no preoperative and postoperative differences.

Of interest, such quality-of-life measures as the patient's perception of general vision and near vision improved by 16-25 points in the AMD group and 8-20 points in the Stargardt macular dystrophy group, even though the data did not support these findings.

Serious adverse effects did occur in this study. Four eyes developed cataract progression, one eye developed endophthalmitis, and one eye developed severe vitreous inflammation. Although these complications were not directly linked to the ESCs, the methodology for placing the cells was responsible for the complications. Neither the outcome measures nor the adverse effects were linked to the quantity of transplanted cells, indicating that further research is needed to determine the optimal number of cells to transplant.


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