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.

Elicitation of Health State Utility Values in Retinitis Pigmentosa by Time Trade-off in the United Kingdom.

Introduction: Retinitis pigmentosa (RP) is an inherited retinal pathology associated with "night blindness" and progressive loss of peripheral vision, in some cases leading to complete blindness. Health state utility values are required for activities such as modelling disease burden or the cost-effectiveness of new interventions. The current study aimed to generate utility values for health states of varying levels of functional vision in RP, with members of the general public in the UK. Methods: Five health states were defined according to standard clinical measures of visual ability. Health state descriptions were developed following interviews with patients with RP in the UK (n=5). Further interviews were conducted for confirmation with healthcare professionals with specific experience of managing patients with RP in the UK (n=2). Interviews with members of the general public in the UK were conducted to value health states. A time trade-off (TTO) process based on the established Measurement and Valuation of Health (MVH) protocol was used. Due to the ongoing COVID-19 pandemic, all interviews were web-enabled and conducted 1:1 by a trained moderator. Results: In total, n=110 TTO interviews were conducted with members of the UK general public. Mean TTO utility values followed the logical and expected order, with increasing visual impairment leading to decreased utility. Mean values varied between 0.78 ± 0.20 ("moderate impairment"), and 0.33 ± 0.26 ("hand motion" to "no light perception"). Supplementary visual analogue scale (VAS) scores also followed the logical and expected order: mean VAS values varied between 47.95 ± 15.38 ("moderate impairment") and 17.22 ± 12.49 in ("hand motion" to "no light perception"). Discussion: These data suggest that individuals living with RP have substantially impaired quality of life. Utility values for RP have been elicited here using a method and sample that is suitable for economic modelling and health technology assessment purposes.

Tele-ophthalmology for age-related macular degeneration during the COVID-19 pandemic and beyond.

INTRODUCTION: COVID-19 has disrupted how ophthalmic practice is conducted worldwide. One patient population that may suffer from poor outcomes during the pandemic are those with age-related macular degeneration (AMD). Many practices are performing some form of tele-ophthalmology services for their patients, and guidance is needed on how to maintain continuity of care amongst patients with AMD using tele-ophthalmology. METHODS: A literature search was conducted, ending 1 August 2020, to identify AMD outcomes and telecare management strategies that could be used during the COVID-19 pandemic. RESULTS: 237 total articles were retrieved, 56 of which were included for analysis. Four American Academy of Ophthalmology and Center for Disease Control web resources were also included. DISCUSSION: Risk-stratification models have been developed that let providers readily screen existing patients for their future risk of neovascular AMD (nAMD). When used with at-home monitoring devices to detect nAMD, providers may be able to determine who should be contacted via tele-ophthalmology for screening. Telemedicine triage can be used for new complaints of vision loss to determine who should be referred to a retinal specialist for management of suspected nAMD. To increase access and provider flexibility, smartphone fundus photography images sent to a centralized tele-ophthalmology service can aid in the detection of nAMD. Considerations should also be made for COVID-19 transmission, and tele-ophthalmology can be used to screen patients for the presence of COVID-19 prior to in-person office visits. Tele-ophthalmology has additional utility in connecting with nursing home, rural, and socioeconomically disadvantaged patients in the post-pandemic period.

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.

Accuracy of Using Generative Adversarial Networks for Glaucoma Detection: Systematic Review and Bibliometric Analysis.

BACKGROUND: Glaucoma leads to irreversible blindness. Globally, it is the second most common retinal disease that leads to blindness, slightly less common than cataracts. Therefore, there is a great need to avoid the silent growth of this disease using recently developed generative adversarial networks (GANs). OBJECTIVE: This paper aims to introduce a GAN technology for the diagnosis of eye disorders, particularly glaucoma. This paper illustrates deep adversarial learning as a potential diagnostic tool and the challenges involved in its implementation. This study describes and analyzes many of the pitfalls and problems that researchers will need to overcome to implement this kind of technology. METHODS: To organize this review comprehensively, articles and reviews were collected using the following keywords: ("Glaucoma," "optic disc," "blood vessels") and ("receptive field," "loss function," "GAN," "Generative Adversarial Network," "Deep learning," "CNN," "convolutional neural network" OR encoder). The records were identified from 5 highly reputed databases: IEEE Xplore, Web of Science, Scopus, ScienceDirect, and PubMed. These libraries broadly cover the technical and medical literature. Publications within the last 5 years, specifically 2015-2020, were included because the target GAN technique was invented only in 2014 and the publishing date of the collected papers was not earlier than 2016. Duplicate records were removed, and irrelevant titles and abstracts were excluded. In addition, we excluded papers that used optical coherence tomography and visual field images, except for those with 2D images. A large-scale systematic analysis was performed, and then a summarized taxonomy was generated. Furthermore, the results of the collected articles were summarized and a visual representation of the results was presented on a T-shaped matrix diagram. This study was conducted between March 2020 and November 2020. RESULTS: We found 59 articles after conducting a comprehensive survey of the literature. Among the 59 articles, 30 present actual attempts to synthesize images and provide accurate segmentation/classification using single/multiple landmarks or share certain experiences. The other 29 articles discuss the recent advances in GANs, do practical experiments, and contain analytical studies of retinal disease. CONCLUSIONS: Recent deep learning techniques, namely GANs, have shown encouraging performance in retinal disease detection. Although this methodology involves an extensive computing budget and optimization process, it saturates the greedy nature of deep learning techniques by synthesizing images and solves major medical issues. This paper contributes to this research field by offering a thorough analysis of existing works, highlighting current limitations, and suggesting alternatives to support other researchers and participants in further improving and strengthening future work. Finally, new directions for this research have been identified.

Anti-VEGF intravitreal injections in the era of COVID-19: responding to different levels of epidemic pressure.

PURPOSE: Following the first wave of the COVID-19 pandemic in early 2020, the easing of strict measures to reduce its spread has led to a resurgence of cases in many countries at both the national and local level. This article addresses how guidance for ophthalmologists on managing patients with retinal disease receiving intravitreal injections of anti-vascular endothelial growth factor (VEGF) during the pandemic should be adapted to the local epidemic pressure, with more or less stringent measures implemented according to the ebb and flow of the pandemic. METHODS: The Vision Academy's membership of international retinal disease experts analyzed guidance for anti-VEGF intravitreal injections during the COVID-19 pandemic and graded the recommendations according to three levels of increasing epidemic pressure. The revised recommendations were discussed, refined, and voted on by the 14-member Vision Academy Steering Committee for consensus. RESULTS: Protocols to minimize the exposure of patients and healthcare staff to COVID-19, including use of personal protective equipment, physical distancing, and hygiene measures, should be routinely implemented and intensified according to local infection rates and pressure on the hospital/clinic or healthcare system. In areas with many COVID-19-positive clusters, additional measures including pre-screening of patients, postponement of non-urgent appointments, and simplification of complex intravitreal anti-VEGF regimens should be considered. Treatment prioritization for those at greatest risk of irreversible vision loss should be implemented in areas where COVID-19 cases are increasing exponentially and healthcare resources are strained. CONCLUSION: Consistency in monitoring of local infection rates and adjustment of clinical practice accordingly will be required as we move forward through the COVID-19 era. Ophthalmologists must continue to carefully weigh the risk-benefits to minimize the exposure of patients and healthcare staff to COVID-19, ensure that patients receive sight-saving treatment, and avoid the potential long-term impact of prolonged treatment postponement.

Guidance for anti-VEGF intravitreal injections during the COVID-19 pandemic.

PURPOSE: There is an urgent need to address how to best provide ophthalmic care for patients with retinal disease receiving intravitreal injections with anti-vascular endothelial growth factor agents during the ongoing global COVID-19 pandemic. This article provides guidance for ophthalmologists on how to deliver the best possible care for patients while minimizing the risk of infection. METHODS: The Vision Academy's Steering Committee of international retinal disease experts convened to discuss key considerations for managing patients with retinal disease during the COVID-19 pandemic. After reviewing the existing literature on the issue, members put forward recommendations that were systematically refined and voted on to develop this guidance. RESULTS: The considerations focus on the implementation of steps to minimize the exposure of patients and healthcare staff to COVID-19. These include the use of personal protective equipment, adherence to scrupulous hygiene and disinfection protocols, pre-screening to identify symptomatic patients, and reducing the number of people in waiting rooms. Other important measures include triaging of patients to identify those at the greatest risk of irreversible vision loss and prioritization of treatment visits over monitoring visits where possible. In order to limit patient exposure, ophthalmologists should refrain from using treatment regimens that require frequent monitoring. CONCLUSION: Management of patients with retinal disease receiving intravitreal injections during the COVID-19 pandemic will require adjustment to regular clinical practice to minimize the risk of exposure of patients and healthcare staff, and to prioritize those with the greatest medical need. The safety of patients and healthcare staff should be of paramount importance in all decision-making.