Advanced Cell Therapy in Keratoconus

Pilot study shows encouraging results with corneal regenerative treatment in keratoconus. Roibeárd O’hÉineacháin reports

Intrastromal implantation of donor corneal lamina lenticules decellularised or recellularised with autologous adipose-derived adult stem cells (ADASCs) can bring about significant long-term clinical improvement in almost all keratoconus disease parameters, according to a pilot study presented by Mona El Zarif OD, MSc, PhD, and colleagues.

“This pilot investigation opens a new area for the management of keratoconus and may offer a less aggressive treatment than the classical corneal transplant and may therefore also reduce the demand for donor corneas, as several laminas can be used from the same donor cornea,” Dr El Zarif said.

In the phase 1 study—principally led by Jorge L Alió MD, PhD, FEBOphth—Dr El Zarif and her associates randomised 14 advanced keratoconus patients into three treatment groups. The first group underwent injection with ADASCs obtained from elective liposuction into a femtosecond laser-created intrastromal pocket. The second group underwent intrastromal implantation of a 120 µm thick decellularised human donor lenticule, and the third group underwent implantation of a donor lenticule recellularised with ADASCs.

Dr El Zarif noted that at one and three years, uncorrected distance visual acuity improved significantly by one to two logMAR lines in all groups, with no statistically significant difference between them. No patient lost visual acuity. All three groups also showed corrected distance visual acuity improvement, although significantly greater improvements appeared in the ADASC group than in the lamina groups.

In addition, optical coherence tomography (OCT) noted a statistically significant increase in central corneal thickness and volume at the one- and three-year follow-ups in the lamina groups compared to the ADASC group. However, there was no significant difference between the two lamina groups in increased corneal thickness. Scheimpflug corneal topography showed improvement in sagittal curvature, a statistically significant enhancement, and pachymetry improvement in the lamina groups.

Confocal microscopy showed a gradual and significant increase in the cellularity in patients’ anterior and posterior stroma. It also showed significant increase in the mid-corneal stroma in all three groups one year after the surgery compared with the preoperative values. Still, the cell density at the anterior and posterior surfaces and within the lamina was statistically significantly higher in patients that received recellularised laminas than those implanted with decellularised laminas.

Furthermore, in the ADASC-alone group, the stem cells changed progressively to a normal keratocyte-like appearance during the six months post-surgery, becoming more luminous, refringent, and voluminous. In patients with decellularised lenticules, the lamina remained acellular in the first postoperative month but became recellularised with native keratocytes after three months. In the eyes with recellularised lenticules, there was greater number of keratocytes than in the decellularised lenticules at six and twelve months.

Dr Alió and Dr El Zarif added no complications such as haze or infection occurred during the three-year follow-up. Furthermore, all patients recovered full corneal transparency within the first postoperative day, and the increase in corneal cell density was not significantly correlated with the presence of fibrotic tissue.

Dr El Zarif and Dr Alió presented this research at the 39th Congress of the ESCRS in Amsterdam.

Mona El Zarif OD, MSc, PhD, Division of Ophthalmology, Universidad Miguel Hernández, Alicante, Spain monazarifaj@hotmail.com

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