What a tragedy. A mid-March report in the New England Journal of Medicine described the cases of 3 patients with age-related macular degeneration who each underwent bilateral injections of autologous adipose tissue-derived stem cells. The treatments were performed at a Florida clinic, which was listed on ClinicalTrials.gov as participating in a clinical study assessing stem cell therapy for non-neovascular age-related macular degeneration. However, although one patient later reported that she thought she was participating in a trial, the treatments described in this paper were not performed within a research study; each patient paid $5000 for bilateral intravitreous stem cell injections. The resulting complications were immediate and severe. Adverse events experienced within a week after the procedures included vitreous hemorrhage, preretinal and intraretinal hemorrhage, retinal detachment, anterior lens displacement, and glaucoma. These sequelae led to substantial, permanent vision loss in all treated eyes. Whereas preprocedure visual acuity ranged from 20/30 to 20/200 in the 6 eyes injected, acuity at 1 year of follow-up was hand motions or worse in 5 of 6 eyes. One patient was left with no light perception bilaterally.

Unfortunately the widespread enthusiasm for regenerative cures has outpaced the scientific evidence for clinical benefit from these therapies for retinal diseases. Current techniques are still experimental. Only a few stem cell therapies are approved by theUS Food and Drug Administration, and none of these treatments are indicated for retinal disease. Nonetheless, commercial enterprises have sprung up across the United States and worldwide that market stem cell “cures” for ocular ailments ranging from age-related macular degeneration to retinitis pigmentosa to diabetic retinopathy. Many of these clinics claim that their preparation techniques involve minimal manipulation of harvested cells and thereby are exempt from Food and Drug Administration oversight.

How do we prevent similar disasters from happening again? A 3-pronged approach, involving careful oversight and swift punitive actions when appropriate, more effective patient education, and strict adherence to ethical guidelines for individual provider/physician responsibility would help. Some argue that existing regulatory standards are already too stringent for the efficient development of promising new therapies. Flexible and expedited approaches that move novel treatments forward responsibly are important. However, government agencies should make negative consequences clear and swift for unethical enterprises such as the one that blinded the 3 patients described above. As physicians, we should play an active role in educating our patients about the importance of rigorously designed clinical trials to scientifically evaluate new and potentially risky treatments. We also need to be vigilant about thoroughly understanding the safety profiles and any potential adverse events associated with the therapies we deliver.

On the same day this case series was published, contrasting news headlines celebrated the fact that the first human transplantation of retinal pigment epithelial cells differentiated from autologous -induced pluripotent stem cells had been successfully performed in a Japanese patient with neovascular age-related macular degeneration. Over 1 year, the transplanted sheet of cells remained essentially intact based on clinical examination and retinal imaging. One year postoperatively, visual acuity remained stable around 20/200. A second patient participating in the study who had cells harvested did not undergo transplantation because of moderate response to anti-VEGF therapy and concerns regarding genetic changes that occurred in the induced pluripotent stem cells. The outcomes of this study based on a single patient might not seem earth-shattering. However, this was the kind of measured, responsible approach with careful study participant selection and thorough documentation of quality and safety checks that is sorely needed in the field.

Many of us, patients and physicians alike, are excited by the dawn of a new era in regenerative medicine. Stem cell approaches have the potential to revolutionize standard care approaches. This sense of optimism is a vital part of encouraging new development of promising therapies. At the same time, we owe it to our patients and to ourselves to ensure careful oversight and meticulous clinical trial evaluation of regenerative therapies as we search for new cures for retinal disease.
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