The San Diego View

By Michael J. Ammar, MD
Retina Consultants San Diego

Dear SDCOS friends,

We're so excited to announce the return of Retina Corner! Educating and fostering discussion on important topics in the field of retina is something Nik London and I are very passionate about. We have greatly enjoyed working so closely with the SDCOS community and discussing the various articles over the years. We hope that you find these topics useful and valuable. If you ever have any questions or requests please let us know! We can't wait to continue our collaboration of excellence in eye care for the SD community.

For this month’s Retina Corner I wanted to discuss something that all of you will get asked about from time to time. Something popularized in movies, books, and science fiction. Something that may one day revolutionize the medical field. The topic I am referring to is stem cell therapy.

Stem cell therapy is an exciting concept that has the potential to restore vision in patients with even the most advanced retinal conditions. Stem cells can differentiate into various cell types, including retinal cells, and can potentially be used to replace damaged or lost tissue. This article aims to provide an update on the current state of stem cell therapies for retinal disease.

There are several phase 1/2 clinical trials that have either been completed or are currently active investigating the safety and efficacy of stem cell therapy for retina conditions. Trials have looked at patients with dry macular degeneration, wet macular degeneration, retinitis pigmentosa, Stargardt macular dystrophy, and central retinal vein occlusions. Three different approaches are being investigated: intravitreal injection of stem cells, subretinal injection of stem cells, and subretinal implantation of a stem cell scaffold. Additionally, there are 2 types of pluripotent stem cells used in clinical trials: human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). Embryonic stem cells are derived from a preimplantation embryo about 4 to 5 days after fertilization. For this reason, the use of these allogeneic hESCs raises ethical issues. In contrast, iPSCs are obtained by taking adult somatic cells and genetically reprogramming the cells to behave like ESCs. This approach avoids ethical and rejection issues. Multipotent stem cells are also being explored in clinical trials for retinal disease. These multipotent cells are partially differentiated and have a more limited potential to differentiate into various cells.

Two phase 1/2 open-label clinical trials sponsored by Astellas Pharma have been conducted in eyes with vision loss from Stargardt macular degeneration using subretinal injection of hESC-RPE cell suspensions. Both studies showed that this treatment was feasible and relatively well tolerated except for a few eyes that developed epiretinal membranes and some participants who developed side effects from systemic immunosuppression. Unfortunately, the visual gain noted in the first study was not seen in the second study. Another trial sponsored by Regenerative Patch Technologies is evaluating the safety and feasibility of transplanting hESC-RPE cells grown as a monolayer in eyes with geographic atrophy secondary to dry AMD. The RPE monolayer is grown in a scaffold and the implant is surgically placed under the macula in the area of geographic atrophy. After 1 year, the clinical trial reported that the implant was well tolerated. There was no associated immune or inflammatory response. Early visual outcomes demonstrated about 60% of patients showing stable or improved vision, whereas about 80% of the patients’ untreated eyes had worsening of vision. More recently, the National Eye Institute has started enrolling for a phase 1/2 clinical trial exploring the safety and tolerability of subretinal placement of iPSC-RPE monolayer grown in a scaffold. Patients with vision loss from geographic atrophy from AMD are being targeted for this clinical trial.

While the available data is still very limited, it has been promising. However, there are potential dangers associated with stem cell therapy. One of the main concerns is the risk of tumor formation. Stem cells have the ability to divide and differentiate into various cell types, which can be beneficial for tissue regeneration. However, if the stem cells divide uncontrollably, they can form tumors. This risk is particularly relevant for iPSCs, which have a higher potential for tumor formation than ESCs. Another concern is the potential for immune rejection. Transplanted stem cells can be recognized as foreign by the patient's immune system, which can result in rejection of the transplanted cells. This risk can be mitigated by using immunosuppressive drugs, but these drugs have their own risks and can have serious side effects.

Unfortunately, many patients with severe vision loss are desperate for treatment options now. To take advantage of this, numerous unregulated fee-for-service clinics referred to as stem cell centers have popped up throughout the country. To appear legitimate, some of these centers have even found a way to get listed on ClinicalTrials.gov. However, many of these centers administer stem cells that have not been adequately characterized or purified, leading to severe irreversible vision loss in some cases. Despite a recent FDA lawsuit against a stem cell center in Florida that blinded a patient with AMD, these clinics persist in their operations. It is crucial for all eye doctors to warn their patients about the risks associated with these unregulated centers and educate them on current data.

Despite these risks, stem cell therapy holds great promise for the treatment of advanced retinal disease. Ongoing research is aimed at developing safer and more effective methods for stem cell therapy, including the use of alternative sources of stem cells and the development of new techniques for controlling stem cell differentiation.

In conclusion, stem cell therapy is a promising new treatment that has the potential to restore vision in patients with advanced retinal disease. While there are potential risks associated with this treatment, ongoing research is aimed at developing safer and more effective methods for stem cell therapy. As this research progresses, stem cell therapy may become an important tool for treating retinal disease and restoring vision to patients who have lost their sight.

I hope you enjoyed this month’s edition of Retina Corner! If you have any questions or if there is ever anything I can help with, please feel free to contact me at any time.

Best wishes, and until next time,

Mike

Michael Ammar, MD
Retina Consultants San Diego
480-323-9196 (cell)
ammar@rcsd.com