Unsafe Ocular Stem Cell Treatments Prevalent

Laird Harrison

July 27, 2018

VANCOUVER, Canada — Experimental stem cell therapies for eye conditions are being offered at dozens of unregulated clinics in the United States, and some of these procedures are harmful, researchers report.

Clinicians should warn their patients against clinics that provide stem cell treatments but offer no other ophthalmologic services, said Ajay Kuriyan, MD, from the University of Rochester Medical Center in New York.

"I can't say that these treatments won't work," he told Medscape Medical News. However, "I can say that we have seen blinding complications at some of these clinics."

Researchers are making progress toward stem cell treatments for ocular diseases in a number of areas. For example, human embryonic stem-cell-derived retinal pigment epithelium cells are being used for geographic atrophy and Stargardt disease. Umbilical cord tissue-derived cells for geographic atrophy are being studied. And retinal pigment epithelium sheets derived from induced pluripotent cells or human embryonic stem cells for neovascular age-related macular degeneration and geographic atrophy are advancing.

But these procedures are still investigational, Kuriyan pointed out.

I can't say that these treatments won't work. I can say that we have seen blinding complications at some of these clinics.

To gauge the extent of the problem, Kuriyan and his colleagues searched the internet for the websites of companies that offer cell therapies for ocular conditions operating in the United States from September 1 to September 16, 2017.

The search turned up 40 companies with 76 clinics. They were in multiple states but were concentrated in California and Florida.

Kuriyan presented results from a content analysis of these websites here at the American Society of Retina Specialists (ASRS) 2018 Annual Meeting.

The businesses offered treatments for 15 ocular conditions. Macular degeneration was the most common, mentioned by 35 companies. It was followed by retinitis pigmentosa, mentioned by 17, and diabetic retinopathy, mentioned by 16. Among the other conditions the clinics purported to treat were blindness and "ophthalmology".

Suspicious Clinics

Two-thirds of the clinics listed autologous adipose-derived stem cells as the material used in the treatment. Another 15% listed autologous bone marrow-derived stem cells. Other materials mentioned included allogenic bone marrow-derived stem cells, placental cells, amniotic, peripheral blood-derived stem cells, and umbilical cord cells.

The use of single-cell sources was reported by 80% of companies; the other 20% reported using multiple-cell sources.

Six companies noted the routes of administration. Eye injections, intravitreal injections, and retrobulbar injections were each mentioned on 20% of these websites. Eye drops, retrofundal injection, sub-Tenon injection, and intraocular with vitrectomy were each mentioned on 10%.

A separate presentation on a search of the PubMed database for ophthalmologic stem cell treatments was presented by Daniel Simhaee, MD, also from the University of Rochester Medical Center.

That search turned up only one published expert opinion describing successful therapy, he reported.

By contrast, 43% of websites advertising ophthalmologic stem cell treatments claim clinically significant benefits, and 52% make vague claims of benefits. Only 13% said benefits are not guaranteed.

"There are some websites that report vague claims, like '90% of patients had some benefit'," Simhaee explained. "It can be very alluring to patients who are desperate for hope, and it seems like some clinics are taking advantage of that."

Desperate Hope

Physicians can help their patients avoid unproven treatments by telling them to look out for clinics charging for treatment, said Wiley Chambers, MD, director of the division of anti-infective and ophthalmology products at the US Food and Drug Administration (FDA), during a discussion after Simhaee's presentation. "I'm not aware of any of these treatments for which the FDA has given permission to charge," he said.

The case of three patients whose eyesight in their better eyes was 20/30 to 20/50 before treatment at U.S. Stem Cell in Weston, Florida, was reported last year by Medscape Medical News. After treatment, their eyesight decreased to 20/200 with no light perception.

Although the FDA has not approved charging for such treatments, each of these patients paid $5000 for the bilateral injections that destroyed their eyesight, Kuriyan said.

Two other cases of patients who suffered adverse events after stem cell treatments have been reported to the ASRS, said Geoffrey Emerson, MD, PhD, chair of the ASRS research and safety in therapeutics committee.

All five of these patients were treated in 2015.

Patients often ask retina specialists about stem cell treatments. "It's a very common question that we encounter," Kuriyan explained. He said he attributes the interest to a combination of news about the progress of legitimate research and slick marketing by the stem cell clinics.

"It's a vulnerable, desperate population," said Emerson, who reported that he, too, often fields questions from patients with macular degeneration. "The patients are going blind. They're losing their reading or driving ability."

"These websites are really well done," Kuriyan pointed out. "Sometimes they have great videos. It's understandable that people can look at these websites and be impressed with them."

Slick Marketing

Some of the companies list trials that are posted on ClinicalTrials.gov, the government website.

"That sometimes confuses patients because they think it's an endorsement," said Kuriyan. But really, "it's just a registry that's meant to be an exhaustive list."

Before patients lost their eyesight after treatment at U.S. Stem Cell, the website listed one trial — under its former name, Bioheart (NCT02024269) — that has since been labeled as "withdrawn."

The FDA "has tried to close loopholes that these companies claim they fall under," Kuriyan said. Although it does not have the resources to search for clinics offering unproven stem cell treatments, it will take action when it receives complaints, said Chambers. "If you tell us about those, that would be very helpful."

U.S. Stem Cell declined to respond to questions posed by Medscape Medical News.

In a letter to the FDA posted on the clinic's website, Kristin Comella, PhD, chief science officer at U.S. Stem Cell, cites the following exemption to FDA regulations for human cell tissue and products (HTC/P): "you are not required to comply with the requirements of this part if you are an establishment that removes HCT/P's from an individual and implants such HCT/P's into the same individual during the same surgical procedure."

However, according to Kuriyan, the stem cell procedure apparently used by U.S. Stem Cell does not fall under this exemption because the cells are not "minimally processed"; the adipose tissue used at the clinic is treated with enzymes and centrifuged. In addition, the cells are not "homologous" because they are harvested from one area of the body and implanted into another.

Last year, the FDA issued a warning letter to U.S. Stem Cell, as reported by Medscape Medical News.

According to the U.S. Stem Cell website, after the adverse events were reported in 2015, the clinic stopped treating macular degeneration.

Kuriyan reports financial relationships to Alimera, Allergan, Regeneron, Genentech, Bayer, and Second Sight. Emerson has disclosed no relevant financial relationships.

American Society of Retina Specialists (ASRS) 2018 Annual Meeting. Presented July 21, 2018.

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