Nanoparticles-mediated CRISPR-Cas9 gene therapy in inherited retinal diseases: applications, challenges, and emerging opportunities.

Inherited Retinal Diseases (IRDs) are considered one of the leading causes of blindness worldwide. However, the majority of them still lack a safe and effective treatment due to their complexity and genetic heterogeneity. Recently, gene therapy is gaining importance as an efficient strategy to address IRDs which were previously considered incurable. The development of the clustered regularly-interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system has strongly empowered the field of gene therapy. However, successful gene modifications rely on the efficient delivery of CRISPR-Cas9 components into the complex three-dimensional (3D) architecture of the human retinal tissue. Intriguing findings in the field of nanoparticles (NPs) meet all the criteria required for CRISPR-Cas9 delivery and have made a great contribution toward its therapeutic applications. In addition, exploiting induced pluripotent stem cell (iPSC) technology and in vitro 3D retinal organoids paved the way for prospective clinical trials of the CRISPR-Cas9 system in treating IRDs. This review highlights important advances in NP-based gene therapy, the CRISPR-Cas9 system, and iPSC-derived retinal organoids with a focus on IRDs. Collectively, these studies establish a multidisciplinary approach by integrating nanomedicine and stem cell technologies and demonstrate the utility of retina organoids in developing effective therapies for IRDs.

Patient Understanding of Nonapproved Stem Cell Therapies for Retinal Disease.

This prospective survey study demonstrates a lack of retina clinic patient knowledge about appropriate stem cell therapy applications for retinal disease.

COVID-19 Launches Retinal Telemedicine into the Next Frontier.

INTRODUCTION: Telemedicine in ophthalmology, and specifically in retinal diseases, has made significant advancements in recent years. The COVID-19 pandemic has launched telehealth into a new era by creating demand from patients and physicians alike, while breaking down previous insurance, reimbursement, access and educational barriers. METHODS: This paper reviews mulitple studies demonstrating the use of telemedicine in managing various retinal conditions before and during the COVID-19 pandemic. CONCLUSION: Moving forward, promising new devices and models of care ensure that tele-retinal care will continue to expand and become a vital part of how we screen, diagnose and monitor retinal diseases.

Immunomodulatory Effects of Hydroxychloroquine and Chloroquine in Viral Infections and Their Potential Application in Retinal Gene Therapy.

Effective treatment of retinal diseases with adeno-associated virus (AAV)-mediated gene therapy is highly dependent on the proportion of successfully transduced cells. However, due to inflammatory reactions at high vector doses, adjunctive treatment may be necessary to enhance the therapeutic outcome. Hydroxychloroquine and chloroquine are anti-malarial drugs that have been successfully used in the treatment of autoimmune diseases. Evidence suggests that at high concentrations, hydroxychloroquine and chloroquine can impact viral infection and replication by increasing endosomal and lysosomal pH. This effect has led to investigations into the potential benefits of these drugs in the treatment of viral infections, including human immunodeficiency virus and severe acute respiratory syndrome coronavirus-2. However, at lower concentrations, hydroxychloroquine and chloroquine appear to exert immunomodulatory effects by inhibiting nucleic acid sensors, including toll-like receptor 9 and cyclic GMP-AMP synthase. This dose-dependent effect on their mechanism of action supports observations of increased viral infections associated with lower drug doses. In this review, we explore the immunomodulatory activity of hydroxychloroquine and chloroquine, their impact on viral infections, and their potential to improve the efficacy and safety of retinal gene therapy by reducing AAV-induced immune responses. The safety and practicalities of delivering hydroxychloroquine into the retina will also be discussed.

Real-world vitreoretinal practice patterns during the 2020 COVID-19 pandemic: a nationwide, aggregated health record analysis.

PURPOSE OF REVIEW: The COVID-19 pandemic has posed an unprecedented challenge to the healthcare community. To reduce disease transmission, national regulatory agencies temporarily recommended curtailment of all nonurgent office visits and elective surgeries in March 2020, including vitreoretinal outpatient care in the USA. The effect of these guidelines on utilization of vitreoretinal care has not been explored to date. RECENT FINDINGS: Retinal outpatient visits, new patient visits, intravitreal antivascular endothelial growth factor injections and in-office multimodal retinal imaging has seen a significant decline in utilization in the early phase of the pandemic. Intravitreal injections were performed at a comparatively higher rate than office visits. Utilization appeared to steadily increase in April 2020. Telemedicine visits, enabled by new national legislation for all areas of medicine, have been adopted to a modest degree by the retina community. SUMMARY: In-office retinal care declined in response to the COVID-19 pandemic and national regulatory guidelines limiting nonurgent care. These trends in practice patterns and care utilization may be of interest to vitreoretinal providers and all ophthalmologists at large.