Multimodal Imaging of Unilateral Acute Maculopathy Associated with Hand, Foot, and Mouth Disease: A Case Series.

We described clinical and multimodal imaging findings in 4 patients with unilateral acute idiopathic maculopathy (UAIM) associated with hand, foot, and mouth disease. Four eyes of 4 patients (3 women and 1 man) with a mean age of 35 years (range: 24-40 years) were included. A bacillary detachment was observed in 3 out of the 4 eyes and was strongly suspected in the remaining eye. This particular detachment was resolved within 5-10 days in our series. A choriocapillaris involvement was supported by the multimodal imaging findings. On indocyanine green angiography, a hypofluorescence was observed throughout the sequence, and OCT angiography showed a defect of the choriocapillaris perfusion. In this case series, a complete multimodal retinal assessment allowed identifying the choriocapillaris as the primary tissue involved in UAIM associated with coxsackie virus infection. In 3 out of our 4 cases, a bacillary detachment with a transient evolution was identified.

Proof of concept for AAV2/5-mediated gene therapy in iPSC-derived retinal pigment epithelium of a choroideremia patient.

Inherited retinal dystrophies (IRDs) comprise a large group of genetically and clinically heterogeneous diseases that lead to progressive vision loss, for which a paucity of disease-mimicking animal models renders preclinical studies difficult. We sought to develop pertinent human cellular IRD models, beginning with choroideremia, caused by mutations in the CHM gene encoding Rab escort protein 1 (REP1). We reprogrammed REP1-deficient fibroblasts from a CHM (-/y) patient into induced pluripotent stem cells (iPSCs), which we differentiated into retinal pigment epithelium (RPE). This iPSC-derived RPE is a polarized monolayer with a classic morphology, expresses characteristic markers, is functional for fluid transport and phagocytosis, and mimics the biochemical phenotype of patients. We assayed a panel of adeno-associated virus (AAV) vector serotypes and showed that AAV2/5 is the most efficient at transducing the iPSC-derived RPE and that CHM gene transfer normalizes the biochemical phenotype. The high, and unmatched, in vitro transduction efficiency is likely aided by phagocytosis and mimics the scenario that an AAV vector encounters in vivo in the subretinal space. We demonstrate the superiority of AAV2/5 in the human RPE and address the potential of patient iPSC-derived RPE to provide a proof-of-concept model for gene replacement in the absence of an appropriate animal model.