Commercial cell therapy clinics yield little evidence

October 22, 2018

Research finds limited publications and dearth of information about side effects

Researchers are assessing the level of evidence for commercially available cell therapy treatments for retinal diseases at cell therapy clinics within the United States.

Reviewed by Daniel Simhaee, MD, and Ajay E. Kuriyan, MD, MS

Promising results from several clinical trials have piqued interest in stem cell therapy. In a phase I/IIa multicenter trial for patients with geographic atrophy secondary to age-related macular degeneration, those who were given subretinal injections of human umbilical derived stem cells noted a “significant increase in vision and central macular thickness: 33 eyes were studied, and at 1 year 35% gained 10 letters or more, and 25% gained 15 letters or more (but had a high risk or retinal perforation/detachment),” said Daniel Simhaee, MD, University of Rochester Medical Center.

However, there are no cell therapies approved by the FDA. That has not deterred some commercial clinics from offering “cell therapy” treatments to patients directly. Ajay E. Kuriyan, MD, MS, University of Rochester Medical Center’s Flaum Eye Institute, treated patients who had undergone bilateral experimental cell injections at one of those clinics. Three patients developed severe bilateral visual loss after they received intravitreal injections of autologous adipose tissue– derived “stem cells.”

In these three patients, the last documented visual acuity on the Snellen eye chart in their better-seeing eye before the injection ranged from 20/30 to 20/50. The patients’ severe visual loss after the injection was associated with ocular hypertension, hemorrhagic retinopathy, vitreous hemorrhage, combined traction and rhegmatogenous retinal detachment, or lens dislocation.

After 1 year, the patients’ visual acuity in their better-seeing eye ranged from 20/200 to no light perception.1

“We thought that these were the only cases that existed, but after our publication,1 we found several other patients at different clinics that also had similar poor outcomes,” Dr. Kuriyan said

That led to trying to determine “what the scope of these cell therapy clinics are and we were amazed to find out that there's about 40 different cell therapy clinic sites just in the U.S. alone. And these sites are advertising to consumers directly about their potential benefits and often times, we found on these websites, that there are vague claims about what they can offer and what they can do for different retinal diseases,” he said.

What the evidence says

The group performed a comprehensive literature search to ascertain what Level of Evidence existed for treatments of retinal diseases at these “cell therapy” clinics and “we basically found a paucity of publications,” Dr. Simhaee said.

“There were no publications that had Levels 1 through 4 evidence based on the Oxford Centre Level of Evidence, and only one with Level 5. There was one case report of a patient who had serpiginous choroidopathy, which was treated with bone marrow stem cells, and was reported to have some improvement in vision.”

But there were multiple publications that disclosed severe visual complications (one Level 4 Evidence, and two with Level 5 Evidence). Beyond those reported by Kuriyan et al.,1 Dr. Simhaee found others. Given the lack of published data, Dr. Simhaee evaluated the stem cell clinics’ websites to determine what risk/benefits the clinics are promoting.

“We found a total of 23 clinics that provide stem cell therapy for retina conditions,” Dr. Simhaee said. “Nearly half claimed there would be clinically significant benefits, and only 10% explicitly stated those benefits are not guaranteed. That's really what made us concerned. This is the information patients are getting, and they're not really being educated on the very real risks of these unapproved procedures.”

Educating patients about risks

Legitimate clinical trials are under way, Dr. Simhaee said.

“Those studies are reported in reputable journals and have a fair amount of patients enrolled in the clinical trials with safety oversight. So, frankly, I was not surprised when we went to the commercial stem cell center websites and were unable to find hard data,” he said.

“Cell therapy has a lot of promise for ophthalmology and these legitimate studies show the potential,” Dr. Kuriyan said.

“We're very eager to see results in a larger number of patients and over a longer period of follow up, but we still have to wait to see them before we can make a full judgment.”

Studies alerting consumers to the potential for unregulated cell therapy and the potential for poor outcomes need to be communicated to the public, he added. Part of patient communication is that legitimate studies are often sponsored by either government or companies, will not ask for payment out-of-pocket, and will likely not bilaterally inject before they can show good safety data.

“If the only service a place offers is cell therapy treatments, that's also a red flag,” Dr. Kuriyan said. “Alerting patients that they should be asking about all treatment options, including observation. If a center does not offer anything beyond cell therapy injections, they may not be legitimate.”

Kuriyan AE, Albini TA, Townsend JH, et al. Vision loss of intravitreal injection of autologous “stem cells” for AMD. N Engl J Med. 2017;376:1047-1053. DOI: 10.1056/NEJMoa160958

Disclosures:

Daniel Simhaee, MD
P: 585/276-3000
This article was adapted from Dr. Simhaee’s presentation at the 2018 meeting of the American Society of Retina Specialists. Drs. Simhaee and Kuriyan do not report any financial disclosures.

References:

1. Kuriyan AE, Albini TA, Townsend JH, et al. Vision loss of intravitreal injection of autologous “stem cells” for AMD. N Engl J Med. 2017;376:1047-1053. DOI: 10.1056/NEJMoa160958