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New assessment tool shows potential of stem cells in restoring LSCD patients’ sight

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January 17, 2014 - A new assessment tool is helping scientists determine which treatments might benefit patients with a type of eye disorder called limbal stem cell deficiency (LSCD). The tool, developed by researchers at University College London and Moorfields Eye Hospital in London and funded by the UK’s National Institute for Health Research Biomedical Research Centre at these institutions, has already shown that the majority of these patients can benefit in the short term from a stem cell transplantation and up to 30 percent are still experiencing better sight three years later, according to the study published in the current issue of STEM CELLS Translational Medicine.

LSCD is an eye disorder in which the stem cells responsible for forming the surface skin of the cornea are destroyed by injury or disease. This results in pain, loss of vision and a cosmetically unpleasant appearance. Many new treatments, including limbal stem cell transplants, are emerging for this condition but their effectiveness remains to be proven.

“Assessing how well they perform has been severely hampered by the lack of biomarkers for LSCD and/or validated tools for determining its severity,” said Alex Shortt, M.D., Ph.D., of University College London’s Institute of Ophthalmology and lead investigator in the study. “In virtually all studies of limbal stem cell transplantation to date the clinical outcome has been assessed subjectively by the investigating clinician. This is clearly open to significant measurement and reporting bias.”

His team’s aims, then, were to design and test the reliability of a new tool for grading LSCD, to define a set of core outcome measures to use in evaluating treatments and to demonstrate the treatments’ impact on two common types of LSCD: a genetic disorder called aniridia and Stevens-Johnson syndrome (SJS), an inflammatory disorder.

They began developing an assessment tool by paring down a list of clinical signs taken from previously published studies to four key LSCD indicators: corneal epithelial haze, superficial corneal neovascularization, corneal epithelial irregularity and corneal epithelial defect. A standardized grading plate was then produced for each of these parameters, ranging from normal to severe. They named their assessment method the Clinical Outcome Assessment in Surgical Trials of Limbal stem cell deficiency [COASTL] tool and validated its performance in 26 patients with varying degrees of LSCD.

Once they had the COASTL tool in place, they used it to evaluate treatment outcomes in 14 patients with aniridia or SJS. All had undergone a limbal epithelial transplantation (allo-CLET), using cells taken from a deceased donor, cultivated in the lab before being transplanted into the recipient.

“The COASTL tool showed that following allo-CLET there was a decrease in LSCD severity and an increase in visual acuity up to 12 months post-treatment, but thereafter LSCD severity and visual acuity progressively deteriorated,” Dr. Shortt said. “However, despite a recurrence of clinical signs, the visual benefit persisted in 30 percent of aniridic and 25 percent of SJS patients at 36 months.

“A reliable method of obtaining objective outcome data for surgical trials of limbal stem cell deficiency will greatly contribute to the effective evaluation of current and new treatments,” said Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.