The clinic offering this treatment was listed as participating in a clinical trial of the intravitreal injection of stem cells derived from autologous adipose tissue as a treatment for non-neovascular macular degeneration. The trial was listed on clinicaltrials.gov, even though it had no investigational new drug application with the FDA. The patients undergoing the procedure had seen the study listed on that website and assumed they were participating in the clinical trial. (The trial itself was withdrawn in September, 2015, before enrollment had actually begun.) The written information given to the patients did not mention any association with a clinical trial, or approval by an institutional review board. All three patients paid $5,000 out of pocket for the procedure.
According to the authors of the NEJM study, subcutaneous adipose tissue was taken from each patient and processed to isolate the putative stem cells. The resulting cells were suspended in a solution of platelet-rich plasma created from the individual’s blood; the mixture was injected intravitreally in both eyes on the same day. Patients were instructed to use one drop of topical moxifloxacin three times a day for three days after the injection.
Within a week, all three of the individuals had presented to other vision clinics (two of them to the Bascom Palmer Eye Institute) suffering loss of vision and other symptoms. Despite extensive treatment and surgery over a period of months, all three suffered debilitating vision loss: One was left with perception of hand motion in one eye and light perception in the other; one was left with 20/200 vision in one eye and perception of hand motion in the other; and the third ended up with no light perception in either eye.
“What makes this type of procedure so risky is the lack of any preclinical (animal) or clinical trial data on the procedure,” says Thomas Albini, MD, an associate professor of clinical ophthalmology at Bascom Palmer Eye Institute at Miami, and co-author of the NEJM paper. “It’s never been properly studied. It seems that clinics have succeeded to some degree in treating patients with joint disease using intra-articular injections; they may have assumed it would be safe to inject into the eye in a similar fashion, but the risk of complications appears to be much higher in the eye.”
Dr. Albini notes that clinicaltrials.gov is overseen by The National Institutes of Health, not the U.S. Food and Drug Administration. “The site was intended to serve as an all-inclusive repository of clinical trials, with a low bar for the inclusion of any particular trial,” he says. “It was not designed to evaluate or approve any of the clinical trials in any way. I think the legislation that created the site didn’t foresee that it could be used as a type of advertising for these clinical procedures.
“When we met the patients, we weren’t sure whether they were in a trial or not,” he continues. “They seemed to think at some point that they were, but there was no evidence in the paperwork they showed us that they did participate in a trial.”
Philip Rosenfeld, MD, PhD, a professor of ophthalmology at the Bascom Palmer Eye Institute at the University of Miami Miller School of Medicine, and a co-author of the NEJM paper, notes that paying for the procedures should have been a red flag. “No reputable clinical trial would charge them for this procedure,” he says. “This type of procedure is experimental—there’s no proven benefit from stem cell transplantation into the eye for any retinal disease.”
Asked why this wasn’t against the law, Dr. Albini notes that many companies and patients believe that stem cell therapies need to be brought to market as quickly as possible. “That’s probably the reason that government agencies like the FDA haven’t pushed for further restriction on these clinics,” he says. “The FDA has clarified multiple times over the past five years that these clinics need to get FDA approval for this type of procedure, but they haven’t followed that with legal action directed at clinics that are clearly in violation of that clarification. It will be interesting to see whether these few cases will push the needle towards more government intervention.”
Dr. Albini notes that there are things a clinician can do to help prevent future problems. “Always insist that intravitreal injections be performed by an ophthalmologist, as suggested by the American Academy of Ophthalmology, or even better, by a retina specialist with experience in treating retinal disease,” he says. “Let your patients know that stem cell clinics often lack the ophthalmic expertise required to perform these procedures, and that even if a clinic does have that expertise—i.e., an ophthalmologist is performing the injection—the procedure has never been studied rigorously and the patient is consequently taking a huge risk. There’s no evidence that the methods used by any clinic result in better vision. On the other hand, we know for sure that these procedures can result in blindness.”
1. Kuriyan AE, Albini TA, Townsend JH, et al. Vision loss after intravitreal injection of autologous “stem cells” for macular degeneration. N Engl J Med 2017;376:1047-53.