Stem cells and lenticules

Intrastromal implantation of donor lenticules that are decellularised or recellularised with autologous adipose-derived autologous stem cells (ADASc) results in improvements in keratoconus parameters without loss of corneal transparency and with no evidence of rejection or any inflammatory reaction at three years’ follow-up, according to a preliminary study presented by Mona Zarif PhD and Prof Jorge Alió MD, PhD, FEBO, Universidad Miguel Hernandez, Alicante, Spain. “All patients in our study had moderate improvements in visual acuity and no patient lost lines. There was also great improvement in stromal thickness parameters and corneal cellularity,” Prof Alió told the 38th Congress of the ESCRS. The phase I study randomised 14 advanced keratoconus patients into three treatment groups. The first group underwent injection of ADASc into a femtosecond laser-created intrastromal pocket. The second group underwent intrastromal implantation of a 120µm thick decellularised human donor lenticule, and the third group underwent implantation of a decellularised human donor lenticule that had been recellularised with autologous ADASc. By 36 months months postoperatively, the corneas in all eyes were transparent. In addition, anterior segment optical coherence tomography showed that corneal thickness had increased by 14.5µm (NS) in the ADASc group and by 117.34µm (p=0.008) in the lenticule groups.Visual acuity improved by a mean of 2.1 lines in the group receiving the ADASc alone (p=0.07) over the first month followed by a stabilisation. In the lenticule groups there was an initial worsening followed by progressive improvement after one month (p=0.04). In terms of refraction, sphere was stable in the stem cell alone group and improved slightly in eyes receiving lenticule implants (p=0.23). Cylinder values deteriorated by -0.563 D in the ADASc alone group (p=0.21) and improved by 0.17D in the stromal lenticule groups(p=-0.46). Mean keratotomy remained stable in the ADASc alone group (p=0.14) but improved significantly by -1.82D (p=0.05) in the stromal lenticule groups. Kmax was also stable in the ADASc alone group with a nonsignificant change of +2.02 D (p=0.14) but improved by -3.04D in the stromal lenticule groups. Confocal microscopy showed that in the ADASc group the stem cells changed progressively to a normal keratocyte-like appearance during the six-month period after surgery. In patients with decellularised lenticules, the lamina remained acellular in the first postoperative month but became recellularised with native keratocytes, after around three months. Recellularised lenticules had a greater number of keratocytes than in the decellularised lenticules at six, 12 and 36 months. This study confirms the feasibility and safety of stem cell advance therapy of corneal stromal diseases as keratoconus. The study is ongoing and a new multi-centre clinical investigation will start in five clinical centres in Spain along this year. Jorge Alió: jlalio@vissum.com