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We appreciate the interest and the comments of the authors of the letter concerning our article “Cellular Therapy With Human Autologous Adipose-Derived Adult Stem Cells for Advanced Keratoconus” published in the recent issue of Cornea.1 Indeed, we agree with many of the postulates of the authors of the letter about the controversial issues that are raised by such unique information in a clinical experience never previously performed and never reported in peer-reviewed journals. In this respect, there are as many questions and open areas as our imagination can envisage when such a new field as that of stem cell therapy for corneal diseases opens for discussion with evidence provided.
Having said that, our article provides only preliminary information, although significant, about the outcomes of corneal stem cell therapy. There is in our original, morphological, and biometrical evidence about the increase in the corneal thickness, and there is further optical coherence tomography evidence that new tissue appears in the corneal interface. Corneal pachymetry was measured by optical coherence tomography and topography, knowing the well-known limitations of conventional scanning-slit corneal topographers in advanced keratoconus cases. However, as mentioned, this increase was mild, and statistical significance could not be demonstrated in such a small study sample.
This increase in tissue is, without doubt, produced by the cells injected as demonstrated in our previous report in the animal model, proving that human adipose–derived stem cells produce human collagen in the rabbit cornea in an identical experience to the one performed here in the human eye.2 This evidence strongly confirms the role of implanted stem cells, as it demonstrated that femtosecond laser activation of keratocytes, although it happens, is not responsible for the increase of corneal tissue at the interface. This is coherent with the total absence of reports about the growth of collagen at the interface in laser-assisted in situ keratomileusis patients.
But the main issue that is raised by this article is the safety of this technique. The cases that have been reported did not lose any line of best-corrected vision. The cases did clinically well, the corneal transparency was maintained, and there were no drawbacks in performing the stromal pocket and injection of the cells into it. Nevertheless, we agree about the necessity of replicating the findings of John Marshall by biomechanical studies of keratoconic corneas to fully validate the method.3 Probably, the use of a carrier of corneal tissue will be the last option for keratoconus to increase the corneal thickness in a calculated way.4
This study forms part of a larger one (available at, the results of which will also be published in the coming months, answering some of the questions raised here, and it is just one part in the puzzle that we are creating to understand better the possibilities of a new type of surgery, regenerative corneal surgery, with potential applications not only in corneal dystrophies and keratoconus but also in other corneal diseases.
The answers to the many questions raised by the evidence provided in our article will be found in the future and indeed will be our main interest in the follow-up of this investigation.
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