An ophthalmologist in the United States calls for increased patient education and regulation after three patients were blinded following a treatment marketed as a stem cell clinical trial.
A recent paper documenting the cases was co-authored by Jeffrey Goldberg, professor and chair of ophthalmology at the Stanford University School of Medicine, and published in The New England Journal of Medicine, a publication of the Massachusetts Medical Society as one of the most prestigious peer-reviewed medical journals in the world. The three patients are all women, ranging in age from 72 to 88. They suffered from macular degeneration, a common, progressive disease of the retina that leads to loss of vision. Before the surgery, the vision in their eyes ranged from 20/30 to 20/200, meaning they can read at 20 feet, or about 6 meters, a letter that people with “normal” vision can read from 30 to 200 feet, or about 9 meters to 60 meters.
Now, the patients are likely to remain blind, said co-author Thomas Albini, an associate professor of clinical ophthalmology at the University of Miami, where two of the patients were treated for complications from the stem cell treatments.Two of the patients learned of the so-called clinical trial on ClinicalTrials.gov, a registry and results database run by the U.S. National Library of Medicine, where it was called “Study to assess the safety and effects of cells injected intravitreal in dry macular degeneration.” “There’s a lot of hope for stem cells, and these types of clinics appeal to patients desperate for care who hope that stem cells are going to be the answer, but in this case these women participated in a clinical enterprise that was off-the-charts dangerous,” Albini was quoted as saying in a news release from Stanford Medicine News Center.
Each patient paid 5,000 U.S. dollars for the procedure. Any clinical trial that has a fee should raise a red flag, said the authors, with Albini adding “I’m not aware of any legitimate research, at least in ophthalmology, that is patient-funded.”At the clinic in Florida, which is not named in the paper, the patients had fat cells removed from their abdomens and a standard blood draw. The fat tissue was processed with enzymes, with the goal of obtaining stem cells. Platelet-dense plasma was isolated from the blood. The cells were then mixed with the platelet-dense plasma and injected into their eyes. Patients reported that the entire process took less than an hour, Albini said.
In addition, the patients had both eyes treated at once, which is another red flag, Albini and Goldberg said, because most doctors would opt for a conservative approach to observe how one eye responds to an experimental treatment before attempting the other eye. Shoddy stem cell preparation may have led to some of the patients’ complications, which could have been caused by injection of a contaminant or the cell wash solution into the eye, Albini said. When injected into the eye, the stem cells also could have changed into myofibroblasts, a type of cell associated with scarring. But even if executed correctly, Goldberg and Albini said, there is no evidence suggesting that the procedure could help restore vision. In fact, there is sparse evidence that adipose-derived stem cells, the type of cells that the clinic claimed to use, are capable of differentiating, or maturing, into retinal pigment epithelium or photoreceptor cells, which play a critical role in macular degeneration and are the cells some researchers are targeting to develop therapies. “There is a lot of very well-founded evidence for the positive potential of stem therapy for many human diseases, but there’s no excuse for not designing a trial properly and basing it on preclinical research,” Goldberg said. The “trial” lacked nearly all of the components of a properly designed clinical trial, including a hypothesis based on laboratory experiments, assignment of a control group and treatment group, collection of data, masking of clinical and patient groups, and plans for follow-up, Goldberg and Albini said.
Listings on ClinicalTrials.gov are not fully scrutinized for scientific soundness, Goldberg noted, adding that it is a “call to awareness for patients, physicians and regulatory agencies of the risks of this kind of minimally regulated, patient-funded research.” “This definitely shows that the lack of oversight can lead to bad players and bad outcomes,” Albini said.