A reply to human retinal pigment epithelium (RPE) transplantation: outcome after autologous RPE-choroid sheet and RPE cell-suspension in a randomised clinical study.

I took great interest in the recent article regarding the retinal pigment epithelium (RPE) transplantation by Falkner-Radler et al. I agree that RPE cell transplantation might be a novel therapeutic option for patients in the antivascular endothelial growth factor (anti-VEGF) era, where antiVEGF fails to improve visual acuity. This is the case in RPE tear, massive subretinal haemorrhage or anti-VEGF non-responders. As already stated by the authors, transplantation of an RPE cell suspension has the disadvantage of not having the extracellular matrix as a scaffold for the cells. Therefore, it is uncertain whether these cells would function well. An RPE cell sheet has been developed to overcome this problem. However, the mechanism of visual acuity improvement in RPE transplantation is influenced by various factors and is poorly understood. Aside from the postoperative complications, one might presume that a functional layer, that is an RPE cell sheet with dense RPE cells, might provide the photoreceptors better support than loose RPE cells, as in RPE cell suspension. Dense RPE cells together with an extracellular matrix in RPE sheet should support all photoreceptors in that region, while loose RPE cells provide support only for some. It is also true that RPE cells might proliferate to some extent but only on a relatively healthy extracellular matrix. This was not replaced in the RPE cell suspension. Nevertheless, the retinal stimuli assessed together with microperimeter and visual acuity might answer this question. One hypothesis might be that if only loose RPE cells are transplanted as in an RPE cell suspension, numerous small scotoma would appear on the region, where the photoreceptors were not supported by the transplanted RPE. This should not be the case in an RPE sheet. The authors stated in the methods that microperimetry was carried out for all patients at the 24-months follow-up. However, no data regarding retinal stimuli was presented in the result section. Retinal stimuli assessed with microperimetry might answer the question, whether the transplanted cells are functioning. This cannot be answered by testing visual acuity alone. We greatly appreciate the study done by Falkner-Radler et al. We hope they will provide the data regarding the microperimetry on the 24-month follow-up visit, since these data reflect the possible advantages or disadvantages of an RPE sheet versus RPE cell suspension.