Eye and Orbit Injuries Caused by Electric Scooters and Hoverboards in the United States.

Introduction: To evaluate eye and orbital injuries in non-powered scooter, electric-scooter (e-scooter), and hoverboard riders in the United States (US) between 2014 and 2019. Methods: The National Electronic Injury Surveillance System (NEISS) was queried for head and neck injuries by body part codes related to non-powered scooters and powered scooters/hoverboards from 2014 to 2019. The NEISS complex sampling design was used to obtain US population projections of injuries and hospital admissions. Keywords were queried in case narratives to analyze trends in location, type, and mechanism of eye and orbit injuries. Results: Since their introduction, a 586% (p=0.01) increase in e-scooter injuries and 866% (p<0.001) increase in hoverboard injuries were observed with an increase in hospital admissions seen in young adults (18-34) in urban areas (e-scooter: 5980% and hoverboard: 479%). Descriptive narratives of the trauma noted eye injuries in 242 unweighted NEISS cases with only 30 cases appropriately documented under body part code 77: eyeball. Eye injuries increased 96.9% during the study period (p=0.23). Specifically, the most common ophthalmic injuries reported included eyebrow (40.9%) and eyelid (11.3%) lacerations, periorbital contusions (18.7%), orbit fractures (6.6%), and corneal abrasions (5.1%). Conclusion: There was a significant increase in both head and neck injury cases and hospital admissions related to e-scooters. Eye and orbit injuries similarly increased but were underreported by body part code compared to injury narratives. Orbital fractures were reported more frequently in injuries from e-scooters than non-powered scooters.

From 2014 to 2019, there were significant increases in both head and neck injuries and hospital admissions related to e-scooters, with eye and orbital injuries similarly increased but underreported by body part code compared to the injury narratives.

Clinical exome sequencing for inherited retinal degenerations at a tertiary care center.

Inherited retinal degenerations are clinically and genetically heterogeneous diseases characterized by progressive deterioration of vision. This study aimed at assessing the diagnostic yield of exome sequencing (ES) for an unselected cohort of individuals with hereditary retinal disorders. It is a retrospective study of 357 unrelated affected individuals, diagnosed with retinal disorders who underwent clinical ES. Variants from ES were filtered, prioritized, and classified using the ACMG recommendations. Clinical diagnosis of the individuals included rod-cone dystrophy (60%), macular dystrophy (20%), cone-rod dystrophy (9%), cone dystrophy (4%) and other phenotypes (7%). Majority of the cases (74%) were singletons and 6% were trios. A confirmed molecular diagnosis was obtained in 24% of cases. In 6% of cases, two pathogenic variants were identified with phase unknown, bringing the potential molecular diagnostic rate to ~ 30%. Including the variants of uncertain significance (VUS), potentially significant findings were reported in 57% of cases. Among cases with a confirmed molecular diagnosis, variants in EYS, ABCA4, USH2A, KIZ, CERKL, DHDDS, PROM1, NR2E3, CNGB1, ABCC6, PRPH2, RHO, PRPF31, PRPF8, SNRNP200, RP1, CHM, RPGR were identified in more than one affected individual. Our results support the utility of clinical ES in the diagnosis of genetically heterogeneous retinal disorders.

Retina Vascular Structures near the Optic Disc and in the Macula in Primary Angle-Closure Suspects.

INTRODUCTION: The main aim of this article was to study the retinal peripapillary and macular vascular structures in eyes with primary angle-closure suspects (PACS) using optical coherence tomography angiography (OCTA). METHODS: In this cross-sectional study, control and PACS subjects were recruited from a community screening. Only one eye per subject was used for analysis. All participants underwent a questionnaire survey, physical and ophthalmic examinations, ocular biometry measurements, and OCTA. We compared basic demographics and vessel structure parameters between control and PACS eyes. Univariate and multivariate linear regression analyses were performed to investigate factors associated with vascular parameters in both groups. RESULTS: Data from 254 subjects including 155 PACS and 99 controls were analyzed. In the peripapillary region, PACS eyes showed similar retina nerve fiber layer (RNFL) and vessel densities (VDs) including and excluding large vessels compared to control eyes. Compared to control eyes, all macular OCTA parameters showed significant differences in PACS eyes, including decreased superficial VD (p = 0.006) and deep VD (p = 0.004), larger fovea avascular zone (FAZ) area (p = 0.006), and longer FAZ perimeter (p = 0.004). Gender (p = 0.039), age (p < 0.001), and Garway-Heath superior hemisphere RNFL (p < 0.001) were risk factors influencing optic disc VD excluding large vessels. Axial length was the major factor affecting macula superficial and deep VDs (p = 0.004 and 0.001 respectively), while PACS was an independent factor associated with larger FAZ perimeter (p = 0.046). CONCLUSION: While PACS and control eyes have comparable RNFL and vascular structure around the optic nerve head, macular vascular structures are significantly different.

Viral Delivery Systems for CRISPR.

The frontiers of precision medicine have been revolutionized by the development of Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR)/Cas9 as an editing tool. CRISPR/Cas9 has been used to develop animal models, understand disease mechanisms, and validate treatment targets. In addition, it is regarded as an effective tool for genome surgery when combined with viral delivery vectors. In this article, we will explore the various viral mechanisms for delivering CRISPR/Cas9 into tissues and cells, as well as the benefits and drawbacks of each method. We will also review the history and recent development of CRISPR and viral vectors and discuss their applications as a powerful tool in furthering our exploration of disease mechanisms and therapies.

Combinatorial Prg4 and Il-1ra Gene Therapy Protects Against Hyperalgesia and Cartilage Degeneration in Post-Traumatic Osteoarthritis.

Osteoarthritis (OA) is a degenerative disease of synovial joints characterized by progressive loss of articular cartilage, subchondral bone remodeling, and intra-articular inflammation with synovitis that results in chronic pain and motor impairment. Despite the economic and health impacts, current medical therapies are targeted at symptomatic relief of OA and fail to alter its progression. Given the complexity of OA pathogenesis, we hypothesized that a combinatorial gene therapy approach, designed to inhibit inflammation with interleukin-1 receptor antagonist (IL-1Ra) while promoting chondroprotection using lubricin (PRG4), would improve preservation of the joint compared to monotherapy alone. Employing two surgical techniques to model mild, moderate and severe posttraumatic OA, we found that combined delivery of helper-dependent adenoviruses (HDVs), expressing IL-1Ra and PRG4, preserved articular cartilage better than either monotherapy in both models as demonstrated by preservation of articular cartilage volume and surface area. This improved protection was associated with increased expression of proanabolic and cartilage matrix genes together with decreased expression of catabolic genes and inflammatory mediators. In addition to improvements in joint tissues, this combinatorial gene therapy prolonged protection against thermal hyperalgesia compared to either monotherapy. Taken together, our results show that a combinatorial strategy is superior to monotherapeutic approaches for treatment of posttraumatic OA.

Disease-Modifying Osteoarthritis Treatment With Interleukin-1 Receptor Antagonist Gene Therapy in Small and Large Animal Models.

OBJECTIVE: Gene therapy holds great promise for the treatment of osteoarthritis (OA) because a single intraarticular injection can lead to long-term expression of therapeutic proteins within the joint. This study was undertaken to investigate the use of a helper-dependent adenovirus (HDAd)-mediated intraarticular gene therapy approach for long-term expression of interleukin-1 receptor antagonist (IL-1Ra) as sustained symptomatic and disease-modifying therapy for OA. METHODS: In mouse models of OA, efficacy of HDAd-IL-1Ra was evaluated by histologic analysis, micro-computed tomography (micro-CT), and hot plate analysis. In a horse OA model, safety and efficacy of HDAd-IL-1Ra were evaluated by blood chemistry, analyses of synovial fluid, synovial membrane, and cartilage, and gross pathology and lameness assessments. RESULTS: In skeletally immature mice, HDAd-IL-1Ra prevented development of cartilage damage, osteophytes, and synovitis. In skeletally immature and mature mice, treatment with HDAd-interleukin-1 receptor antagonist post-OA induction resulted in improved-albeit not significantly-cartilage status assessed histologically and significantly increased cartilage volume, cartilage surface, and bone surface covered by cartilage as assessed by micro-CT. Fewer osteophytes were observed in HDAd-IL-1Ra-treated skeletally immature mice. Synovitis was not affected in skeletally immature or mature mice. HDAd-IL-1Ra protected against disease-induced thermal hyperalgesia in skeletally mature mice. In the horse OA model, HDAd-IL-1Ra therapy significantly improved lameness parameters, indicating efficient symptomatic treatment. Moreover, macroscopically and histologically assessed cartilage and synovial membrane parameters were significantly improved, suggesting disease-modifying efficacy. CONCLUSION: These data from OA models in small and large animals demonstrated safe symptomatic and disease-modifying treatment with an HDAd-expressing IL-1Ra. Furthermore, this study establishes HDAd as a vector for joint gene therapy.

Proteoglycan 4 expression protects against the development of osteoarthritis.

Osteoarthritis (OA) is a common degenerative condition that afflicts more than 70% of the population between 55 and 77 years of age. Although its prevalence is rising globally with aging of the population, current therapy is limited to symptomatic relief and, in severe cases, joint replacement surgery. We report that intra-articular expression of proteoglycan 4 (Prg4) in mice protects against development of OA. Long-term Prg4 expression under the type II collagen promoter (Col2a1) does not adversely affect skeletal development but protects from developing signs of age-related OA. The protective effect is also shown in a model of posttraumatic OA created by cruciate ligament transection. Moreover, intra-articular injection of helper-dependent adenoviral vector expressing Prg4 protected against the development of posttraumatic OA when administered either before or after injury. Gene expression profiling of mouse articular cartilage and in vitro cell studies show that Prg4 expression inhibits the transcriptional programs that promote cartilage catabolism and hypertrophy through the up-regulation of hypoxia-inducible factor 3α. Analyses of available human OA data sets are consistent with the predictions of this model. Hence, our data provide insight into the mechanisms for OA development and offer a potential chondroprotective approach to its treatment.

Quantitative imaging of murine osteoarthritic cartilage by phase-contrast micro-computed tomography.

OBJECTIVE: The mouse is an optimal model organism in which gene-environment interactions can be used to study the pathogenesis of osteoarthritis (OA). The gold standard for arthritis research in mice is based on histopathology and immunohistochemistry, which are labor-intensive, prone to sampling bias and technical variability, and limited in throughput. The aim of this study was to develop a new technique that assesses mouse cartilage by integrating quantitative volumetric imaging techniques. METHODS: A novel mouse model of OA was generated by cruciate ligament transection (CLT) and evaluated by histopathology and immunohistochemistry. Knee joint specimens were then imaged using a new technique that combines high-resolution micro-computed tomography (micro-CT) and phase-contrast optics followed by quantitative analyses. A comparative analysis was also performed in a previously established mouse model of OA generated by destabilization of the medial meniscus (DMM). RESULTS: Phase-contrast micro-CT achieved cellular resolution of chondrocytes and quantitative assessment of parameters such as articular cartilage volume and surface area. In mouse models of OA generated by either CLT or DMM, we showed that phase-contrast micro-CT distinguished control and OA cartilage by providing quantitative measures with high reproducibility and minimal variability. Features of OA at the cellular or tissue level could also be observed in images generated by phase-contrast micro-CT. CONCLUSION: We established an imaging technology that comprehensively assessed and quantified the 2-dimensional and 3-dimensional changes of articular cartilage. Application of this technology will facilitate the rapid and high-throughput assessment of genetic and therapeutic models of OA in mice.