Advanced keratoconus study
Our group has conducted and recently published the first human clinical trial designed to preliminarily evaluate the safety and efficacy of the cellular therapy with mesenchymal stem cells for the corneal stroma.13 We performed a non-randomised and unblind clinical trial [ClinicalTrials.gov; Identifier: NCT02932852], which enrolled patients with advanced keratoconus (stage ≥ IV according to the RETICS keratoconus classification14) who were already candidates for corneal transplantation for their visual rehabilitation.
Five consecutive patients were included, and a suspension containing autologous adipose-derived adult stem cells (ADASC) was transferred into a mid-stromal femtosecond laser-assisted lamellar pocket. All procedures were conducted under topical anaesthesia and without requiring any corneal suture.
Fat containing the stem cells had previously been obtained by elective liposuction (under local anaesthesia) and subsequently processed in the laboratory in order to isolate the autologous ADASC (similar to the methodology reported in our previous experimental studies,2-4 although a certified white chamber was required for the stem cells’ isolation this time, given their human application). (Figure 1.)
There were no intra- or postoperative complications. Corneal transparency was fully recovered to preoperative levels within 48 hours, and any inflammatory reaction or rejection response was documented in the 6-month follow-up to the study (Figure 2).
The mean age of the study patients was 34.2 years and none of them had previously received any ophthalmic surgical intervention. All patients had improved visual function: unaided and corrected distance visual acuities presented an overall improvement of more than one line compared with preoperatively, while best visual acuity with rigid contact lenses showed a total mean improvement of more than two lines.
Conversely, all keratometric parameters presented relative stability. A mild mean improvement of 16.5 µm in the central corneal thickness was detected by anterior segment OCT (Visante) at the sixth month, correlating with the demonstration of newly formed collagen in the majority of the patients – seen as patched hyperreflective areas at the level of the stromal pocket not homogeneously distributed along it (Figure 3).
Implanted ADASC survival was confirmed by confocal biomicroscopy (HRT-3, Heidelberg), where rounded-shape cells were observed in the surgical plane in all cases up to the third postoperative month (Figure 4). By the sixth postoperative month, these cells presented a fusiform shape and were not different from those observed in other stromal planes, assuming this morphologic change as a possible sign of adult keratocyte differentiation of the ADASC.
An interesting finding was a moderate clinical improvement of preoperative anterior stromal scars in one patient along the follow-up. This finding would agree with Dr James Funderburgh’s and other authors’ findings in animal models regarding the potential capability of mesenchymal stem cells to alleviate pre-existing corneal stromal scars.6-9