Ninel Z. Gregori

Bio: Ninel Z. Gregori is an academic researcher from Bascom Palmer Eye Institute. The author has contributed to research in topics: Visual acuity & Cataract surgery. The author has an hindex of 7, co-authored 12 publications receiving 1132 citations.

Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR

Abstract: Retinal gene therapy has shown great promise in treating retinitis pigmentosa (RP), a primary photoreceptor degeneration that leads to severe sight loss in young people. In the present study, we report the first-in-human phase 1/2, dose-escalation clinical trial for X-linked RP caused by mutations in the RP GTPase regulator (RPGR) gene in 18 patients over up to 6 months of follow-up (https://clinicaltrials.gov/: NCT03116113). The primary outcome of the study was safety, and secondary outcomes included visual acuity, microperimetry and central retinal thickness. Apart from steroid-responsive subretinal inflammation in patients at the higher doses, there were no notable safety concerns after subretinal delivery of an adeno-associated viral vector encoding codon-optimized human RPGR (AAV8-coRPGR), meeting the pre-specified primary endpoint. Visual field improvements beginning at 1 month and maintained to the last point of follow-up were observed in six patients.

Macular Spectral-domain Optical Coherence Tomography in Patients with X-linked Retinoschisis.

Abstract: Purpose: The purpose of this study is to evaluate macular anatomy in patients with X-linked retinoschisis (XLRS) using spectral-domain OCT (SD-OCT). Methods: Consecutive observational case series. Clinical features were obtained through retrospective chart review. Only eyes without prior surgical interventions and those scanned with SD-OCT were included. The OCT images were analyzed. Results: Fourteen eyes of 7 males with XLRS scanned with SD-OCT, age 5 to 45 years, were identified. On clinical examination, stellate spoke-like cystic maculopathy was present in 9 eyes, and an atrophic foveal lesion in 5 eyes. SD-OCT revealed cystoid spaces accounting for retinal splitting in the inner nuclear layer in 12 eyes, and outer plexiform layer in two eyes of one patient. A few small cysts, not accounting for the foveal splitting, were seen in the outer nuclear layer in 4 eyes and in the ganglion cell layer and/or nerve fiber layer in 6 eyes. Conclusions: SD-OCT localized the foveomacular retinoschisis in XLRS to the retinal layers deeper than the nerve fiber layer. In the present study, the foveomacular schisis was seen most frequently in the inner nuclear layer.

Relationship between the morphology of the foveal avascular zone, retinal structure, and macular circulation in patients with diabetes mellitus.

Abstract: Diabetic Retinopathy (DR) is an extremely severe and common degenerative disease. The purpose of this study was to quantify the relationship between various parameters including the Foveal Avascular Zone (FAZ) morphology, retinal layer thickness, and retinal hemodynamic properties in healthy controls and patients with diabetes mellitus (DM) with and with no mild DR (MDR) using Spectral-Domain Optical Coherence Tomography (Spectralis SDOCT, Heidelberg Engineering GmbH, Germany) and the Retinal Function Imager (Optical Imaging, Ltd., Rehovot, Israel). Our results showed a higher FAZ area and diameter in MDR patients. Blood flow analysis also showed that there is a significantly smaller venous blood flow velocity in MDR patients. Also, a significant difference in roundness was observed between DM and MDR groups supporting the development of asymmetrical FAZ expansion with worsening DR. Our results suggest a potential anisotropy in the mechanical properties of the diabetic retina with no retinopathy that may trigger the FAZ elongation in a preferred direction resulting in either thinning or thickening of intraretinal layers in the inner and outer segments of the retina as a result of autoregulation. A detailed understanding of these relationships may facilitate earlier detection of DR, allowing for preservation of vision and better clinical outcomes.

Reproducibility and comparison of visual acuity obtained with sightbook mobile application to near card and snellen chart.

Abstract: Purpose:To investigate test–retest reproducibility of visual acuities obtained with a popular mobile application (app) and to explore the agreement with the standard clinic charts.Methods:Records of patients who had visual acuity measured during the same routine clinic visit with Snellen chart, Rose

Autologous Induced Stem-Cell–Derived Retinal Cells for Macular Degeneration

Abstract: We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age-related macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age-related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing. A surgery that included the removal of the neovascular membrane and transplantation of the autologous iPSC-derived RPE cell sheet under the retina was performed in one of the patients. At 1 year after surgery, the transplanted sheet remained intact, best corrected visual acuity had not improved or worsened, and cystoid macular edema was present. (Funded by Highway Program for Realization of Regenerative Medicine and others; University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number, UMIN000011929.)

Stem cells: past, present, and future.

Abstract: In recent years, stem cell therapy has become a very promising and advanced scientific research topic. The development of treatment methods has evoked great expectations. This paper is a review focused on the discovery of different stem cells and the potential therapies based on these cells. The genesis of stem cells is followed by laboratory steps of controlled stem cell culturing and derivation. Quality control and teratoma formation assays are important procedures in assessing the properties of the stem cells tested. Derivation methods and the utilization of culturing media are crucial to set proper environmental conditions for controlled differentiation. Among many types of stem tissue applications, the use of graphene scaffolds and the potential of extracellular vesicle-based therapies require attention due to their versatility. The review is summarized by challenges that stem cell therapy must overcome to be accepted worldwide. A wide variety of possibilities makes this cutting edge therapy a turning point in modern medicine, providing hope for untreatable diseases.

Gene therapy clinical trials worldwide to 2017: An update

Abstract: To date, almost 2600 gene therapy clinical trials have been completed, are ongoing or have been approved worldwide. Our database brings together global information on gene therapy clinical activity from trial databases, official agency sources, published literature, conference presentations and posters kindly provided to us by individual investigators or trial sponsors. This review presents our analysis of clinical trials that, to the best of our knowledge, have been or are being performed worldwide. As of our November 2017 update, we have entries on 2597 trials undertaken in 38 countries. We have analysed the geographical distribution of trials, the disease indications (or other reasons) for trials, the proportions to which different vector types are used, and the genes that have been transferred. Details of the analyses presented, and our searchable database are available via The Journal of Gene Medicine Gene Therapy Clinical Trials Worldwide website at: http://www.wiley.co.uk/genmed/clinical. We also provide an overview of the progress being made in gene therapy clinical trials around the world, and discuss key trends since the previous review, namely the use of chimeric antigen receptor T cells for the treatment of cancer and advancements in genome editing technologies, which have the potential to transform the field moving forward.