Re: Farmas USA
OCAT
Respuesta de Lanza, Schwartz y Anglade:
We thank Janet Sunness and Guo-You Zhang and colleagues for their comments on our Article.1 Sunness asserts that transplantation of human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE) into patients with advanced dry age-related macular degeneration and Stargardt's disease needs to be tested. We report only visual improvements as noted during the course of a phase 1 safety trial. As mentioned in our Article,1 many potential explanations are available for these observations other than an actual functional improvement, including those suggested by Sunness. However, the area of the macula transplanted in our patients intentionally excluded the foveal centre to which Sunness refers, and instead targeted a transition zone that included undetectable, compromised, and healthy photoreceptors. This choice of transplant site was guided with multimodal imaging done preoperatively and intended to transplant an area that recapitulated the central macula earlier in the course of the disease. Again, safety was the primary endpoint studied. All vision improvements came as surprise to the investigators. All patient assessments were assessed by masked vision examiners with expertise in low vision rehabilitation.
Perhaps more importantly, accumulating evidence suggests that photoreceptor inner segments or cell bodies might survive in a state that is difficult to detect in some forms of macular degeneration.2 Thus, if biological plausibility of transplanted stem-cell progeny conferring a regenerative signal to neighbouring tissues is discounted, a rescue effect of dormant cell types might still be noted. Therefore, we respectfully disagree with the statement that transplantation of stem-cell-derived retinal pigment epithelium cells cannot restore vision; we are confident that this is an open question and are hopeful that future studies will help answer it.
We agree with the potential value of microperimetric assessment. Many of our patients have undergone many microperimetric tests before and after transplantation and some even seemed to show improved thresholds and fixation in the transplant sites. However, after further scrutiny and consultation with renowned experts in the specialty, the results were deemed to be immaterial and ultimately without meaning. Microperimetry is an evolving science and is very difficult to accurately study in eyes with poor fixation. Despite these hurdles, microperimetry will be part of future clinical trial protocols.
We agree with Zhang and colleagues that our phase 1 safety trial studying hESC-RPE contained 18 patients and, thus, assumptions of absolute safety should be avoided. Furthermore, we appreciate and agree that a complete dose–response curve has not been generated in this phase 1 safety trial, and thank them for the common suggestion that stem-cell-derived photoreceptors should be combined with hESC-RPE. Finally, we agree that immunosuppression regimens have to be optimised.
«Después de nada, o después de todo/ supe que todo no era más que nada.»
