Stem cell treatment: What could possibly go wrong with procedure?

June 8, 2019

Surgeon offers some cautionary tales about unfortunate cases he has encountered

Stem cell therapies for ocular diseases often are of unproven efficacy and may result in vision loss, notes one surgeon.

Reviewed by Thomas A. Albini, MD

Stem cell technology is a rapidly growing, highly lucrative industry serving thousands of patients. With the opportunities it can present, people with nefarious intentions will seek to take advantages of patients with chronic diseases who are looking for a glimmer of hope. However, ophthalmologists are warning that the booming industry, which promises better health, including improved vision, can leave patients disappointed, frustrated, and in worse condition after the treatments.

According to Thomas A. Albini, MD, businesses have opened their doors to target patients with macular degeneration, diabetic retinopathy, and retinitis pigmentosa with sophisticated TV ads that tout expensive stem cell treatments. One company provides a customized stem cell eye drop using autologous stem cells for treating end-stage glaucoma.

The drops cost $5,000 per bottle and when questioned, the company told Dr. Albini that the more months of therapy the patient had the better and no data supports the treatment. Dr. Albini, professor clinical ophthalmology, Bascom Palmer Eye Institute, University of Miami, said he began to focus on the industries after two patients came to his practice after undergoing stem cell treatments for age-related macular degeneration (AMD) at a Broward County, FL, clinic.

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Patient saw a ‘specialist’

The first patient, a 78-year-old woman had undergone bilateral simultaneous intravitreal injections of autologous adipose tissue-derived stem cells, which were administered by a “stem cell specialist” who was not an MD. The woman’s previous retina specialist told Dr. Albini that the patient had wet AMD treated with multiple anti-vascular endothelial growth factor drug injections; the visual acuities (VAs) at that time were 20/50 and 20/100 in the right and left eyes, respectively.

Two days after the stem cell injection, she presented with minimal inflammation, vitreal hemorrhages, and the presence of an adipose tissue mass bilaterally. On days 16 and 38, rhegmatogenous retinal detachments developed in the right and left eyes; surgery was performed. The VAs at 12 months were hand motions and 20/200. The second patient, a 72-year-old woman, presented with pain and decreased VA to counting fingers three days after having been treated at the same stem cell clinic.

She had a history of dry AMD with VAs of 20/60 and 20/30 in the right and left eyes, respectively. Bilateral stem cell injections were administered resulting in bilateral crystalline lens subluxation, vitreous hemorrhage, and an acute intraocular pressure spike to 60 mm Hg. Emergency bilateral vitrectomies were performed for endophthalmitis, during which a retinal detachment was found in one eye.

The VAs at 12 months were no light perception bilaterally. Both cases were reported to the Therapeutic Surveillance Committee of the American Society of Refractive Surgeons, which knew of a third patient treated at the same clinic. That patient had dry AMD and following treatment after 12 months the VAs were hand motions and light perception in the right and left eyes, respectively, as a result of traction rhegmatogenous detachments and proliferative vitreoretinopathy.

Her previous VAs had been 20/40 and 20/200. Potential causes of the issues in these cases, noted Dr. Albini, were stem cell contamination, use of trypsin or collagenase during stem cell isolation, and effects of growth factors, fibroblasts, and other cells in the vitreous and blood leading to traction development.

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Stem cell regulation

These biologics are regulated by the FDA’s Center for Biologics and Research, which requires companies to register biologics and secure a license to market them. Problems have arisen as a result of the regulatory language that divides cell therapies into high-risk and low-risk therapies.

And herein lies the rub from the standpoint of how companies interpret the regulation. Low risk means that an autologous cell is going to be used in a patient for the same purpose for which it originally served, minimal manipulation of the tissue is performed, and the tissue is injected into the patient on the same day in the same procedure. This does not require FDA regulation.

When those conditions are not met, the procedure is considered high risk and requires FDA regulation. Dr. Albini noted the FDA states stem cell procedures, the majority of which are joint injections, violate the regulations and should not be performed. At Bascom Palmer, 26 eyes of 13 patients have been treated after undergoing a stem cell treatment for a variety of ocular diseases.

“The VAs were poor in these patients,” Dr. Albini explained. “Intravitreal injection was the most common method of delivering the stem cells. There was an association in the patients between the injections and development of epiretinal membranes and traction retinal detachments in eight patients.”

The FDA decided to prosecute clinics providing these unproven stem cell treatments but are giving them three years to make changes before they face prosecution. There is a moratorium on further stem cell injections into the eye, Dr. Albini noted.

Red flags

Practitioners who are not eye specialists should not be treating eye disease, or charging patients for participating in research, i.e., patient-funded research. Patients have paid from $5,000 to $40,000 to participate in a clinical trial, and the clinics that are not registered with the FDA, even though they claim to be FDA compliant. The clinics also have performed the bilateral application of an experimental procedure.

“Patients are desperate for alternative therapies for chronic diseases. Intravitreal cellular therapies can potentially cause posterior vitreous detachments and retinal detachments,” Dr. Albini concluded.

“This shows the importance of the regulatory environment that we live in. If we did not have these hurdles to go over to identify successful therapies, it would be hard to know which of these therapies really work and which do not and the line between hope and hoax would be blurred. The FDA does protect patients.”

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Disclosures:

Thomas A. Albini, MD
E: talbini@med.miami.edu
This article was adapted from a presentation by Dr. Albini at the 2018 American Association of Ophthalmology meeting. Dr. Albini has no fi nancial interest in any aspect of this report.


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