A stem cell-based graft therapy using patients’ tissue successfully treated people with severe neurotrophic keratitis, significantly correcting cornea damage and vision in all cases, a pilot study demonstrated.
The study, “Treatment of Limbal Stem Cell Deficiency in the Setting of Neurotrophic Keratopathy,” was published in the Journal of International Translational Medicine.
Neurotrophic keratitis is an eye disorder that affects the cornea — the transparent outer layer of the eye; it functions like a window that focuses light entering the eye.
It is caused by the malfunction of nerves that serve the cornea, reducing sensitivity and tear production in the outer layer of the cornea (epithelium). In more severe cases, the inner cornea (stroma) can breakdown in a process known as stromal melting.
The loss of corneal nerves also may lead to a deficiency in stem cells in the limbus, located at the border between the cornea and the white of the eye (the sclera), which may further contribute to impaired healing.
There are three stages to the disease; stage 1 refers to a mild disease of the epithelium, in stage 2 there is persistent damage to the epithelium, and stage 3 is characterized by severe damage that include stromal melting and formation of ulcers and holes.
In Stage 3 cases, patients may require surgery to prevent further stromal melting, which can involve conjunctival flaps (tissue from inside of the eyelids), corneal glues, or grafts with corneas or human amniotic membrane, which is a protective layer made from human placental-based tissue.
A cell-based therapy known as cultured limbal epithelial transplantation (CLET) is an alternative approach in which stems cells from a patient’s eye limbus are collected, cultured into a sheet of limbal epithelium cells, then transplanted onto the cornea of the same patient.
This approach was used by a team of researchers based at the Medical University-Sofia in Bulgaria to treat 10 patients with severe stage 3 neurotrophic keratitis.
The patients were age 39 to 71, with characteristic clinical signs for at least six months. Infectious diseases were ruled out as a cause, and patients’ eyes were tested for inflammation, and optical scans were done before and one month after the intervention.
Stem cells from biopsied limbal tissue were collected from each patient, cultured in a lab, and then the limbal epithelial sheet was spread over the cornea of the affected eye. Following the procedure, bandage contact lenses were not applied.
All patients were treated with anti-inflammatory and antibiotic eye drops, which were tapered and replaced by artificial tears.
Patients were assessed the day after surgery, two weeks later, then at one and six months. The primary outcomes were defined as the complete growth of epithelial cells on the cornea, reduced growth of new blood vessels, improved cornea transparency, and better vision.
In all cases, all primary outcomes were met. After the procedure, optical scans showed complete new growth of a stable, thick epithelial layer on the cornea and the reduction of scar tissue in the stroma. There was a reduction in the growth of blood vessels, and the corneas were more transparent in all cases, which improved over six months.
All patients experienced a statistically significant improvement in vision and reported better subjective symptoms.
No rejection or inflammatory conditions were observed, and the biopsy did not affect the donor’s eye.
“Our report provides evidence to support the use of cultured limbal epithelial cell transplantation as a treatment alternative for neurotrophic ulcers,” the researchers wrote.
“Further research is needed to demonstrate how it compares to simple [amniotic membrane] transplantation and other treatment options for [Neurotrophic keratitis],” they added.