Patient and Public Involvement and Engagement in the Development of a Platform Clinical Trial for Parkinson's Disease: An Evaluation Protocol.

Background: Patient and public involvement and engagement (PPIE) in the design of trials is important, as participant experience critically impacts delivery. The Edmond J Safra Accelerating Clinical Trials in PD (EJS ACT-PD) initiative is a UK consortium designing a platform trial for disease modifying therapies in PD. Objective: The integration of PPIE in all aspects of trial design and its evaluation throughout the project. Methods: PwP and care partners were recruited to a PPIE working group (WG) via UK Parkinson's charities, investigator patient groups and participants of a Delphi study on trial design. They are supported by charity representatives, trial delivery experts, researchers and core project team members. PPIE is fully embedded within the consortium's five other WGs and steering group. The group's terms of reference, processes for effective working and PPIE evaluation were co-developed with PPIE contributors. Results: 11 PwP and 4 care partners have supported the PPIE WG and contributed to the development of processes for effective working. A mixed methods research-in-action study is ongoing to evaluate PPIE within the consortium. This includes the Patient Engagement in Research Scale -a quantitative PPIE quality measure; semi-structured interviews -identifying areas for improvement and overall impressions of involvement; process fidelity- recording adherence; project documentation review - identifying impact of PPIE on project outputs. Conclusions: We provide a practical example of PPIE in complex projects. Evaluating feasibility, experiences and impact of PPIE involvement in EJS ACT-PD will inform similar programs on effective strategies. This will help enable future patient-centered research.

Systematic review and appraisal of quality, definitions and treatment recommendations of clinical guidelines for glaucoma suspects.

BACKGROUND: To appraise the quality of clinical practice guidelines for glaucoma suspects, and to assess their consistency for how a 'glaucoma suspect' is defined and their recommendations for treatment initiation for such individuals. METHODS: This study included all documents that self-identified as a 'guideline' and provided recommendation(s) for the clinical care of glaucoma suspects. The quality of eligible guidelines was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. RESULTS: From 1196 records retrieved from comprehensive searches and two records manually included, 20 clinical practice guidelines were deemed eligible. Based on an appraisal using the AGREE II instrument, 16 (80%) guidelines had ≤2 domains with scores >66%. Overall, the lowest scoring domains were for applicability, editorial independence and stakeholder involvement. There was relatively poor agreement across the guidelines for what defines a 'glaucoma suspect' or 'primary open angle glaucoma [POAG] suspect', as well as the recommendations and criteria for treatment initiation in these populations. There was better agreement for the definition and recommendations for treatment initiation for 'primary angle closure suspects'. CONCLUSIONS: There is substantial room to improve the methodological quality of most current international clinical guidelines for glaucoma suspects. Clinicians should consider this finding when using such guidelines to inform their care of glaucoma suspects. Substantial variation in the definition of a POAG suspect and recommendations for treatment initiation underscores important gaps in the current evidence for the accurate prediction of glaucoma development and treatment effectiveness in these individuals.

Potential Retinal Biomarkers in Alzheimer's Disease.

Alzheimer's disease (AD) represents a major diagnostic challenge, as early detection is crucial for effective intervention. This review examines the diagnostic challenges facing current AD evaluations and explores the emerging field of retinal alterations as early indicators. Recognizing the potential of the retina as a noninvasive window to the brain, we emphasize the importance of identifying retinal biomarkers in the early stages of AD. However, the examination of AD is not without its challenges, as the similarities shared with other retinal diseases introduce complexity in the search for AD-specific markers. In this review, we address the relevance of using the retina for the early diagnosis of AD and the complex challenges associated with the search for AD-specific retinal biomarkers. We provide a comprehensive overview of the current landscape and highlight avenues for progress in AD diagnosis by retinal examination.

Increased Glaucoma Case-finding Through Routine Optical Coherence Tomography in Optometry Practice.

OBJECTIVE: Timely detection of glaucoma is key to preventing or delaying vision loss. This study aimed to assess whether the routine use of optical coherence tomography (OCT) by optometrists for detection of glaucomatous changes in the optic nerve and retina increased glaucoma referrals to ophthalmologists. DESIGN: This study was a retrospective review of routinely-collected electronic medical records of patients from a chain of 331 optometry practices in Australia. PARTICIPANTS: Electronic medical records were reviewed for every patient aged 18-99 years who attended an included practice between January 1 and July 31, 2019. METHODS: Odds of referral for glaucoma assessment were compared between practices performing OCT routinely on all patients (OCT practices, n=175) and without OCT (non-OCT practices, n=20). A subset of referrals were assessed by ophthalmologists to determine the false positive referral rate. MAIN OUTCOME MEASURES: The primary outcome measure of this study was referral to an ophthalmologist for glaucoma assessment. A secondary outcome was the rate of false positive referrals, analysed in a subset of patients referred for glaucoma assessment. RESULTS: Records from 994,461 patients (59% female) were included and 10,475 (1.1%) were referred for glaucoma assessment. Most referrals were associated with normal intraocular pressure (non-OCT practices: n=496, 66%; OCT practices: n=6,603, 68%). Referral for glaucoma was higher in OCT practices (n=9,719, 1.1%) compared to non-OCT practices (n=756, 0.8%, age-, gender- and location-adjusted odds ratio 1.39, 95% confidence interval 1.10-1.76). Of 318 referred patients (3%, all from OCT practices) for whom ophthalmologist feedback was available, 68 (21%) were considered not to have glaucoma. CONCLUSIONS: The routine use of OCT in optometric practice may lead to more timely glaucoma detection and prevention of avoidable vision loss.

Correction: The Minderoo-Monaco Commission on Plastics and Human Health.

[This corrects the article DOI: 10.5334/aogh.4056.].

Health Care for Children in Immigrant Families: Key Considerations and Addressing Barriers.

One in four US children is a child in an immigrant family. Children in immigrant families (CIF) have distinct health and health care needs that vary by documentation status, countries of origin, and health care and community experience caring for immigrant populations. Health insurance access and language services are fundamental to providing health care to CIF. Promoting health equity for CIF requires a comprehensive approach to both the health and social determinants of health needs of CIF. Child health providers can promote health equity for this population through tailored primary care services and partnerships with immigrant-serving community organizations.

Systematic Underestimation of Visual Sensitivity Loss on Microperimetry: Implications for Testing Protocols in Clinical Trials.

Purpose: To examine whether systematic changes in visual sensitivity measurements on microperimetry occur over tests within the same session and whether these changes vary according to the level of visual sensitivity loss. Methods: Eighty individuals with glaucoma or atrophic age-related macular degeneration underwent three microperimetry tests in one eye during one session using the 4-2 staircase strategy. Changes in mean sensitivity (MS) and pointwise sensitivity (PWS) between the first and second test pairs were examined, with PWS was examined separately based on its average value across the three tests in 6-dB bins. The coefficient of repeatability (CoR) for MS between each sequential test pair was also calculated. Results: There was a significant decline in MS from the first to second test (P = 0.001), but no significant difference in MS was seen between the second and third tests (P = 0.562). This significant decline in the first test pair was observed in locations with an average PWS of <6 dB or between 6 to 12 dB and between 12 to 18 dB (P < 0.001), but not for all other average PWS bins (P ≥ 0.337). The CoR of MS was significantly lower in the second compared to the first test pair (1.4 dB and 2.5 dB, respectively; P < 0.001). Conclusions: The 4-2 staircase strategy conventionally used on microperimetry testing systematically underestimates visual sensitivity loss on the first test. Translational Relevance: The consistency and accuracy of visual sensitivity measurements on microperimetry in clinical trials could be markedly improved by using estimates from an initial test to seed subsequent tests and excluding this first test from analyses.

Immunobiology of a rationally-designed AAV2 capsid following intravitreal delivery in mice.

Adeno-associated virus serotype 2 (AAV2) is a viral vector that can be used to deliver therapeutic genes to diseased cells in the retina. One strategy for altering AAV2 vectors involves the mutation of phosphodegron residues, which are thought to be phosphorylated/ubiquitinated in the cytosol, facilitating degradation of the vector and the inhibition of transduction. As such, mutation of phosphodegron residues have been correlated with increased transduction of target cells, however, an assessment of the immunobiology of wild-type and phosphodegron mutant AAV2 vectors following intravitreal (IVT) delivery to immunocompetent animals is lacking in the current literature. In this study, we show that IVT of a triple phosphodegron mutant AAV2 capsid is associated with higher levels of humoral immune activation, infiltration of CD4 and CD8 T-cells into the retina, generation of splenic germinal centre reactions, activation of conventional dendritic cell subsets, and elevated retinal gliosis compared to wild-type AAV2 capsids. However, we did not detect significant changes in electroretinography arising after vector administration. We also demonstrate that the triple AAV2 mutant capsid is less susceptible to neutralisation by soluble heparan sulphate and anti-AAV2 neutralising antibodies, highlighting a possible utility for the vector in terms of circumventing pre-existing humoral immunity. In summary, the present study highlights novel aspects of rationally-designed vector immunobiology, which may be relevant to their application in preclinical and clinical settings.

Evaluation of a Community COVID-19 Vaccine Ambassador Train-the-Trainer Program.

Racially minoritized groups are more likely to experience COVID-19 vaccine hesitancy and have lower vaccination rates.  As part of a multi-phase community-engaged project, we developed a train-the-trainer program in response to a needs assessment. "Community vaccine ambassadors" were trained to address COVID-19 vaccine hesitancy. We evaluated the program's feasibility, acceptability, and impact on participant confidence for COVID-19 vaccination conversations. Of the 33 ambassadors trained, 78.8% completed the initial evaluation; nearly all reported gaining knowledge (96.8%) and reported a high confidence with discussing COVID-19 vaccines (93.5%). At two-week follow-up, all respondents reported having a COVID-19 vaccination conversation with someone in their social network, reaching an estimated 134 people. A program that trains community vaccine ambassadors to deliver accurate information about COVID-19 vaccines may be an effective strategy for addressing vaccine hesitancy in racially minoritized communities.

The Minderoo-Monaco Commission on Plastics and Human Health.

Background: Plastics have conveyed great benefits to humanity and made possible some of the most significant advances of modern civilization in fields as diverse as medicine, electronics, aerospace, construction, food packaging, and sports. It is now clear, however, that plastics are also responsible for significant harms to human health, the economy, and the earth's environment. These harms occur at every stage of the plastic life cycle, from extraction of the coal, oil, and gas that are its main feedstocks through to ultimate disposal into the environment. The extent of these harms not been systematically assessed, their magnitude not fully quantified, and their economic costs not comprehensively counted. Goals: The goals of this Minderoo-Monaco Commission on Plastics and Human Health are to comprehensively examine plastics' impacts across their life cycle on: (1) human health and well-being; (2) the global environment, especially the ocean; (3) the economy; and (4) vulnerable populations-the poor, minorities, and the world's children. On the basis of this examination, the Commission offers science-based recommendations designed to support development of a Global Plastics Treaty, protect human health, and save lives. Report Structure: This Commission report contains seven Sections. Following an Introduction, Section 2 presents a narrative review of the processes involved in plastic production, use, and disposal and notes the hazards to human health and the environment associated with each of these stages. Section 3 describes plastics' impacts on the ocean and notes the potential for plastic in the ocean to enter the marine food web and result in human exposure. Section 4 details plastics' impacts on human health. Section 5 presents a first-order estimate of plastics' health-related economic costs. Section 6 examines the intersection between plastic, social inequity, and environmental injustice. Section 7 presents the Commission's findings and recommendations. Plastics: Plastics are complex, highly heterogeneous, synthetic chemical materials. Over 98% of plastics are produced from fossil carbon- coal, oil and gas. Plastics are comprised of a carbon-based polymer backbone and thousands of additional chemicals that are incorporated into polymers to convey specific properties such as color, flexibility, stability, water repellence, flame retardation, and ultraviolet resistance. Many of these added chemicals are highly toxic. They include carcinogens, neurotoxicants and endocrine disruptors such as phthalates, bisphenols, per- and poly-fluoroalkyl substances (PFAS), brominated flame retardants, and organophosphate flame retardants. They are integral components of plastic and are responsible for many of plastics' harms to human health and the environment.Global plastic production has increased almost exponentially since World War II, and in this time more than 8,300 megatons (Mt) of plastic have been manufactured. Annual production volume has grown from under 2 Mt in 1950 to 460 Mt in 2019, a 230-fold increase, and is on track to triple by 2060. More than half of all plastic ever made has been produced since 2002. Single-use plastics account for 35-40% of current plastic production and represent the most rapidly growing segment of plastic manufacture.Explosive recent growth in plastics production reflects a deliberate pivot by the integrated multinational fossil-carbon corporations that produce coal, oil and gas and that also manufacture plastics. These corporations are reducing their production of fossil fuels and increasing plastics manufacture. The two principal factors responsible for this pivot are decreasing global demand for carbon-based fuels due to increases in 'green' energy, and massive expansion of oil and gas production due to fracking.Plastic manufacture is energy-intensive and contributes significantly to climate change. At present, plastic production is responsible for an estimated 3.7% of global greenhouse gas emissions, more than the contribution of Brazil. This fraction is projected to increase to 4.5% by 2060 if current trends continue unchecked. Plastic Life Cycle: The plastic life cycle has three phases: production, use, and disposal. In production, carbon feedstocks-coal, gas, and oil-are transformed through energy-intensive, catalytic processes into a vast array of products. Plastic use occurs in every aspect of modern life and results in widespread human exposure to the chemicals contained in plastic. Single-use plastics constitute the largest portion of current use, followed by synthetic fibers and construction.Plastic disposal is highly inefficient, with recovery and recycling rates below 10% globally. The result is that an estimated 22 Mt of plastic waste enters the environment each year, much of it single-use plastic and are added to the more than 6 gigatons of plastic waste that have accumulated since 1950. Strategies for disposal of plastic waste include controlled and uncontrolled landfilling, open burning, thermal conversion, and export. Vast quantities of plastic waste are exported each year from high-income to low-income countries, where it accumulates in landfills, pollutes air and water, degrades vital ecosystems, befouls beaches and estuaries, and harms human health-environmental injustice on a global scale. Plastic-laden e-waste is particularly problematic. Environmental Findings: Plastics and plastic-associated chemicals are responsible for widespread pollution. They contaminate aquatic (marine and freshwater), terrestrial, and atmospheric environments globally. The ocean is the ultimate destination for much plastic, and plastics are found throughout the ocean, including coastal regions, the sea surface, the deep sea, and polar sea ice. Many plastics appear to resist breakdown in the ocean and could persist in the global environment for decades. Macro- and micro-plastic particles have been identified in hundreds of marine species in all major taxa, including species consumed by humans. Trophic transfer of microplastic particles and the chemicals within them has been demonstrated. Although microplastic particles themselves (>10 µm) appear not to undergo biomagnification, hydrophobic plastic-associated chemicals bioaccumulate in marine animals and biomagnify in marine food webs. The amounts and fates of smaller microplastic and nanoplastic particles (MNPs <10 µm) in aquatic environments are poorly understood, but the potential for harm is worrying given their mobility in biological systems. Adverse environmental impacts of plastic pollution occur at multiple levels from molecular and biochemical to population and ecosystem. MNP contamination of seafood results in direct, though not well quantified, human exposure to plastics and plastic-associated chemicals. Marine plastic pollution endangers the ocean ecosystems upon which all humanity depends for food, oxygen, livelihood, and well-being. Human Health Findings: Coal miners, oil workers and gas field workers who extract fossil carbon feedstocks for plastic production suffer increased mortality from traumatic injury, coal workers' pneumoconiosis, silicosis, cardiovascular disease, chronic obstructive pulmonary disease, and lung cancer. Plastic production workers are at increased risk of leukemia, lymphoma, hepatic angiosarcoma, brain cancer, breast cancer, mesothelioma, neurotoxic injury, and decreased fertility. Workers producing plastic textiles die of bladder cancer, lung cancer, mesothelioma, and interstitial lung disease at increased rates. Plastic recycling workers have increased rates of cardiovascular disease, toxic metal poisoning, neuropathy, and lung cancer. Residents of "fenceline" communities adjacent to plastic production and waste disposal sites experience increased risks of premature birth, low birth weight, asthma, childhood leukemia, cardiovascular disease, chronic obstructive pulmonary disease, and lung cancer.During use and also in disposal, plastics release toxic chemicals including additives and residual monomers into the environment and into people. National biomonitoring surveys in the USA document population-wide exposures to these chemicals. Plastic additives disrupt endocrine function and increase risk for premature births, neurodevelopmental disorders, male reproductive birth defects, infertility, obesity, cardiovascular disease, renal disease, and cancers. Chemical-laden MNPs formed through the environmental degradation of plastic waste can enter living organisms, including humans. Emerging, albeit still incomplete evidence indicates that MNPs may cause toxicity due to their physical and toxicological effects as well as by acting as vectors that transport toxic chemicals and bacterial pathogens into tissues and cells.Infants in the womb and young children are two populations at particularly high risk of plastic-related health effects. Because of the exquisite sensitivity of early development to hazardous chemicals and children's unique patterns of exposure, plastic-associated exposures are linked to increased risks of prematurity, stillbirth, low birth weight, birth defects of the reproductive organs, neurodevelopmental impairment, impaired lung growth, and childhood cancer. Early-life exposures to plastic-associated chemicals also increase the risk of multiple non-communicable diseases later in life. Economic Findings: Plastic's harms to human health result in significant economic costs. We estimate that in 2015 the health-related costs of plastic production exceeded $250 billion (2015 Int$) globally, and that in the USA alone the health costs of disease and disability caused by the plastic-associated chemicals PBDE, BPA and DEHP exceeded $920 billion (2015 Int$). Plastic production results in greenhouse gas (GHG) emissions equivalent to 1.96 gigatons of carbon dioxide (CO2e) annually. Using the US Environmental Protection Agency's (EPA) social cost of carbonmetric, we estimate the annual costs of these GHG emissions to be $341 billion (2015 Int$).These costs, large as they are, almost certainly underestimate the full economic losses resulting from plastics' negative impacts on human health and the global environment. All of plastics' economic costs-and also its social costs-are externalized by the petrochemical and plastic manufacturing industry and are borne by citizens, taxpayers, and governments in countries around the world without compensation. Social Justice Findings: The adverse effects of plastics and plastic pollution on human health, the economy and the environment are not evenly distributed. They disproportionately affect poor, disempowered, and marginalized populations such as workers, racial and ethnic minorities, "fenceline" communities, Indigenous groups, women, and children, all of whom had little to do with creating the current plastics crisis and lack the political influence or the resources to address it. Plastics' harmful impacts across its life cycle are most keenly felt in the Global South, in small island states, and in disenfranchised areas in the Global North. Social and environmental justice (SEJ) principles require reversal of these inequitable burdens to ensure that no group bears a disproportionate share of plastics' negative impacts and that those who benefit economically from plastic bear their fair share of its currently externalized costs. Conclusions: It is now clear that current patterns of plastic production, use, and disposal are not sustainable and are responsible for significant harms to human health, the environment, and the economy as well as for deep societal injustices.The main driver of these worsening harms is an almost exponential and still accelerating increase in global plastic production. Plastics' harms are further magnified by low rates of recovery and recycling and by the long persistence of plastic waste in the environment.The thousands of chemicals in plastics-monomers, additives, processing agents, and non-intentionally added substances-include amongst their number known human carcinogens, endocrine disruptors, neurotoxicants, and persistent organic pollutants. These chemicals are responsible for many of plastics' known harms to human and planetary health. The chemicals leach out of plastics, enter the environment, cause pollution, and result in human exposure and disease. All efforts to reduce plastics' hazards must address the hazards of plastic-associated chemicals. Recommendations: To protect human and planetary health, especially the health of vulnerable and at-risk populations, and put the world on track to end plastic pollution by 2040, this Commission supports urgent adoption by the world's nations of a strong and comprehensive Global Plastics Treaty in accord with the mandate set forth in the March 2022 resolution of the United Nations Environment Assembly (UNEA).International measures such as a Global Plastics Treaty are needed to curb plastic production and pollution, because the harms to human health and the environment caused by plastics, plastic-associated chemicals and plastic waste transcend national boundaries, are planetary in their scale, and have disproportionate impacts on the health and well-being of people in the world's poorest nations. Effective implementation of the Global Plastics Treaty will require that international action be coordinated and complemented by interventions at the national, regional, and local levels.This Commission urges that a cap on global plastic production with targets, timetables, and national contributions be a central provision of the Global Plastics Treaty. We recommend inclusion of the following additional provisions:The Treaty needs to extend beyond microplastics and marine litter to include all of the many thousands of chemicals incorporated into plastics.The Treaty needs to include a provision banning or severely restricting manufacture and use of unnecessary, avoidable, and problematic plastic items, especially single-use items such as manufactured plastic microbeads.The Treaty needs to include requirements on extended producer responsibility (EPR) that make fossil carbon producers, plastic producers, and the manufacturers of plastic products legally and financially responsible for the safety and end-of-life management of all the materials they produce and sell.The Treaty needs to mandate reductions in the chemical complexity of plastic products; health-protective standards for plastics and plastic additives; a requirement for use of sustainable non-toxic materials; full disclosure of all components; and traceability of components. International cooperation will be essential to implementing and enforcing these standards.The Treaty needs to include SEJ remedies at each stage of the plastic life cycle designed to fill gaps in community knowledge and advance both distributional and procedural equity.This Commission encourages inclusion in the Global Plastic Treaty of a provision calling for exploration of listing at least some plastic polymers as persistent organic pollutants (POPs) under the Stockholm Convention.This Commission encourages a strong interface between the Global Plastics Treaty and the Basel and London Conventions to enhance management of hazardous plastic waste and slow current massive exports of plastic waste into the world's least-developed countries.This Commission recommends the creation of a Permanent Science Policy Advisory Body to guide the Treaty's implementation. The main priorities of this Body would be to guide Member States and other stakeholders in evaluating which solutions are most effective in reducing plastic consumption, enhancing plastic waste recovery and recycling, and curbing the generation of plastic waste. This Body could also assess trade-offs among these solutions and evaluate safer alternatives to current plastics. It could monitor the transnational export of plastic waste. It could coordinate robust oceanic-, land-, and air-based MNP monitoring programs.This Commission recommends urgent investment by national governments in research into solutions to the global plastic crisis. This research will need to determine which solutions are most effective and cost-effective in the context of particular countries and assess the risks and benefits of proposed solutions. Oceanographic and environmental research is needed to better measure concentrations and impacts of plastics <10 µm and understand their distribution and fate in the global environment. Biomedical research is needed to elucidate the human health impacts of plastics, especially MNPs. Summary: This Commission finds that plastics are both a boon to humanity and a stealth threat to human and planetary health. Plastics convey enormous benefits, but current linear patterns of plastic production, use, and disposal that pay little attention to sustainable design or safe materials and a near absence of recovery, reuse, and recycling are responsible for grave harms to health, widespread environmental damage, great economic costs, and deep societal injustices. These harms are rapidly worsening.While there remain gaps in knowledge about plastics' harms and uncertainties about their full magnitude, the evidence available today demonstrates unequivocally that these impacts are great and that they will increase in severity in the absence of urgent and effective intervention at global scale. Manufacture and use of essential plastics may continue. However, reckless increases in plastic production, and especially increases in the manufacture of an ever-increasing array of unnecessary single-use plastic products, need to be curbed.Global intervention against the plastic crisis is needed now because the costs of failure to act will be immense.

Intraocular Pressure Spikes Following iStent Inject and the Relationship to Aqueous Outflow in Open Angle Glaucoma.

PRCIS: Adding trabecular bypass surgery (TBS) to phacoemulsification creates unpredictable short-term intraocular pressure (IOP) control that may be undesirable for patients with advanced glaucoma. Aqueous outflow (AO) responses after TBS are complex and probably multifactorial. PURPOSE: To assess IOP spikes in patients with open angle glaucoma up to 1 month after iStent inject and their relationship to AO patterns measured by hemoglobin video imaging (HVI). PARTICIPANTS AND METHODS: We studied IOP for 4 weeks after TBS with iStent inject in 105 consecutive eyes with open angle glaucoma (6 TBS only and 99 combined with phacoemulsification). The change in IOP after surgery at each time point was compared with baseline measurements and the prior postoperative visit. IOP-lowering medications were stopped on the day of surgery in all patients. A smaller pilot study of 20 eyes (TBS only = 6 and combined = 14) underwent concurrent HVI to observe and quantify perioperative AO. Aqueous column cross-sectional area (AqCA) of one nasal and one temporal aqueous vein was calculated at each time point, and qualitative observations were documented. An additional 5 eyes were studied after phacoemulsification only. RESULTS: Mean IOP for the entire cohort (preoperative 17.3 ± 5.6 mm Hg) was lowest the day after TBS (13.1 ± 5.0 mm Hg) and peaked at 1 week (17.2 ± 8.0 mm Hg), before stabilizing by 4 weeks (15.2 ± 5.2 mm Hg; P < 0.00001). The same IOP pattern was seen when separating the group into a larger cohort without HVI (respectively 15.9 ± 3.2 mm Hg, 12.8 ± 4.9 mm Hg, 16.4 ± 7.4 mm Hg, and 14.1 ± 4.1 mm Hg; N = 85, P < 0.00001) and the smaller HVI pilot study (respectively 21.4 ± 9.9 mm Hg, 14.2 ± 4.9 mm Hg, 20.2 ± 9.7 mm Hg, and 18.9 ± 7.6 mm Hg; N = 20, P < 0.001). More than 30% IOP elevation above baseline occurred in 13.3% of the entire cohort at 1 week after surgery. This increased to 46.7% when IOP was compared with 1 day after surgery. Inconsistent AqCA values and patterns of aqueous flow were demonstrated after TBS. AqCA after phacoemulsification alone was maintained or increased within 1 week in all 5 eyes. CONCLUSION: After iStent inject surgery in patients with open angle glaucoma, intraocular spikes were most commonly seen at 1 week. AO patterns were variable and additional studies are needed to understand the pathophysiology underlying IOP responses after this procedure.

Improving adeno-associated viral (AAV) vector-mediated transgene expression in retinal ganglion cells: comparison of five promoters.

Recombinant adeno-associated viral vectors (AAVs) are an effective system for gene transfer. AAV serotype 2 (AAV2) is commonly used to deliver transgenes to retinal ganglion cells (RGCs) via intravitreal injection. The AAV serotype however is not the only factor contributing to the effectiveness of gene therapies. Promoters influence the strength and cell-selectivity of transgene expression. This study compares five promoters designed to maximise AAV2 cargo space for gene delivery: chicken ß-actin (CBA), cytomegalovirus (CMV), short CMV early enhancer/chicken ß-actin/short ß-globulin intron (sCAG), mouse phosphoglycerate kinase (PGK), and human synapsin (SYN). The promoters driving enhanced green fluorescent protein (eGFP) were examined in adult C57BL/6J mice eyes and tissues of the visual system. eGFP expression was strongest in the retina, optic nerves and brain when driven by the sCAG and SYN promoters. CBA, CMV, and PGK had moderate expression by comparison. The SYN promoter had almost exclusive transgene expression in RGCs. The PGK promoter had predominant expression in both RGCs and AII amacrine cells. The ubiquitous CBA, CMV, and sCAG promoters expressed eGFP in a variety of cell types across multiple retinal layers including Müller glia and astrocytes. We also found that these promoters could transduce human retina ex vivo, although expression was predominantly in glial cells due to low RGC viability. Taken together, this promoter comparison study contributes to optimising AAV-mediated transduction in the retina, and could be valuable for research in ocular disorders, particularly those with large or complex genetic cargos.

Fast Progressors in Glaucoma: Prevalence Based on Global and Central Visual Field Loss.

PURPOSE: To determine the prevalence of fast global and central visual field (VF) progression in individuals with glaucoma under routine care. DESIGN: Observational study. PARTICIPANTS: Six hundred ninety-three eyes of 461 individuals with glaucoma followed up over a median of 4.5 years. METHODS: This study included (1) patients at a private ophthalmology clinic in Melbourne, Australia, and (2) individuals in 2 prospective longitudinal observational studies across 3 sites in the United States. All individuals had a diagnosis of glaucoma and were under routine care, and had performed 5 or more reliable 24-2 VF tests over a 1- to 5-year period. Ordinary least squares regression analyses were used to calculate the rate of global mean deviation (MD) change over time and the rate of the mean total deviation values of the 12 test locations within the central 10° region (MTD10) for each eye. MAIN OUTCOME MEASURES: Prevalence of progression based on the rate of MD and the MTD10 change across various fixed cutoffs and cutoffs based on the estimated normal distribution (from the positive slopes). RESULTS: Based on the MD and the MTD10, 12.5% and 11.7% of the eyes, respectively, exhibited a rate of change that was less than -1.0 dB/year (being a rate that typically is defined as "fast progression" for MD values), and 29.0% of the eyes showed a change of less than -0.5 dB/year on MTD10. Furthermore, 12.7% and 9.1% of the eyes exhibited a rate of change that exceeded the 1% cutoff of the estimated normal distribution MD and the MTD10 values, respectively. CONCLUSIONS: This study found that approximately 1 in 8 eyes with glaucoma receiving routine care showed fast progression based on global MD values (< -1.0 dB/year) and that nearly 1 in 3 eyes showed a < -0.5 dB/year decline centrally. These findings highlight the clinical importance of assessing progressive central VF loss and reinforce the need for new therapies to prevent functional disability in a notable proportion of individuals who continue to exhibit fast progression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Barriers and Facilitators to Prevention and Care of COVID-19 Infection in Cincinnati Latinx Families: a Community-Based Convergent Mixed Methods Study.

BACKGROUND: Latinx populations have experienced disproportionately high case rates of COVID-19 across the USA. Latinx communities in non-traditional migration areas may experience greater baseline day-to-day challenges such as a lack of resources for immigrants and insufficient language services. These challenges may be exacerbated by the COVID-19 pandemic. OBJECTIVE: This article describes the results of an initial community health needs assessment to better understand the prevention and care of COVID-19 infection in the Cincinnati Latinx community. METHODS: We used convergent mixed methods to examine barriers and facilitators to COVID-19 prevention and care for those with infection. RESULTS: Latinx adults ≥ 18 years old completed 255 quantitative surveys and 17 qualitative interviews. Overarching mixed methods domains included knowledge, prevention, work, challenges, and treatment. Quantitative results largely reinforced qualitative results (confirmation). Certain quantitative and qualitative results, however, diverged and expanded insights related to caring for COVID-19 infection among Latinx adults (expansion). There were infrequent contradictions between quantitative and qualitative findings (discordance). Primary barriers for the Latinx community during the COVID-19 pandemic included insecurities in food, jobs, housing, and immigration. Key facilitators included having trusted messengers of health-related information. CONCLUSION: Public health interventions should be centered on community partnerships and the use of trusted messengers. Wraparound services (including resources for immigrants) are essential public health services. Close partnership with employers is essential as lack of sick leave and mask supplies were more frequent barriers than knowledge. These findings emerged from experiences during the COVID-19 pandemic but likely generalize to future public health crises.

RNA-targeting strategies as a platform for ocular gene therapy.

Genetic medicine is offering hope as new therapies are emerging for many previously untreatable diseases. The eye is at the forefront of these advances, as exemplified by the approval of Luxturna® by the United States Food and Drug Administration (US FDA) in 2017 for the treatment of one form of Leber Congenital Amaurosis (LCA), an inherited blindness. Luxturna® was also the first in vivo human gene therapy to gain US FDA approval. Numerous gene therapy clinical trials are ongoing for other eye diseases, and novel delivery systems, discovery of new drug targets and emerging technologies are currently driving the field forward. Targeting RNA, in particular, is an attractive therapeutic strategy for genetic disease that may have safety advantages over alternative approaches by avoiding permanent changes in the genome. In this regard, antisense oligonucleotides (ASO) and RNA interference (RNAi) are the currently popular strategies for developing RNA-targeted therapeutics. Enthusiasm has been further fuelled by the emergence of clustered regularly interspersed short palindromic repeats (CRISPR)-CRISPR associated (Cas) systems that allow targeted manipulation of nucleic acids. RNA-targeting CRISPR-Cas systems now provide a novel way to develop RNA-targeted therapeutics and may provide superior efficiency and specificity to existing technologies. In addition, RNA base editing technologies using CRISPR-Cas and other modalities also enable precise alteration of single nucleotides. In this review, we showcase advances made by RNA-targeting systems for ocular disease, discuss applications of ASO and RNAi technologies, highlight emerging CRISPR-Cas systems and consider the implications of RNA-targeting therapeutics in the development of future drugs to treat eye disease.

Survey of perspectives of people with inherited retinal diseases on ocular gene therapy in Australia.

Many gene therapies are in development for treating people with inherited retinal diseases (IRD). We hypothesized that potential recipients of gene therapy would have knowledge gaps regarding treatment. We aimed to assess knowledge, attitudes, and perceptions of genetic therapies among potential recipients with IRD, using a novel instrument we designed (Attitudes to Gene Therapy-Eye (AGT-Eye)) and their associations with demographic data, self-reported visual status, and tools assessing quality of life and attitudes toward clinical trials using a community-based cross-sectional survey of Australian adults with IRD. AGT-Eye, overall quality of life EQ-5D-5L, National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) and Patient Attitudes to Clinical Trials (PACT-22) instruments were administered. Six hundred and eighty-one people completed the study, 51.7% women of mean age 53.5 years (SD ± 15.8). Most participants (91.6%) indicated they would likely accept gene therapy if it was available to them or family members. However, only 28.3% agreed that they had good knowledge of gene therapy. Most obtained information about gene therapy from the internet (49.3%). Respondents with post-graduate degrees scored highest compared to other educational levels on methods (p < 0.001) and outcomes (p = 0.003) and were more likely to see economic value of treatment (p = 0.043). Knowledge gaps were present regarding methods and outcomes of gene therapy. This survey has shown high level of interest in the IRD community for gene therapies, and highlights areas for improved clinician and patient education.

Daily Meditation Practice for Managing Glaucoma Patients' Attitudes and Acceptance.

PRCIS: Overall, 63% of glaucoma patients agreed to 45-60 minutes of daily meditation. Predictors of accepting meditation included previous meditation practice, a diagnosis of glaucoma <1 year, and having a marital status of "single". PURPOSE: To explore patients' acceptance and barriers towards 45-60 minutes daily meditation for glaucoma management and to identify glaucoma patients with higher perceived stress levels who may benefit more from meditation practice. METHODS: Glaucoma patients attending the Royal Victorian Eye and Ear Hospital, Melbourne, Australia outpatient department were invited to complete a patient survey. This survey explored if patients would agree to 45-60 minutes of daily meditation and included the Determinants of Meditation Practice Inventory and Perceived Stress Scale questionnaires. Questionnaire scores were compared across participants' clinical and demographic characteristics using Student t test, ANOVA, and multiple-linear-regression analysis. RESULTS: Of the 123 eligible patients screened, 100 completed the survey (81.3%). Sixty-three (63%) patients would agree to 45-60 minutes of daily meditation if advised by their doctor. Univariate analysis showed increased acceptance of meditation (lower Determinants of Meditation Practice Inventory scores) to be associated with agreeing to meditate 45-60 minutes daily ( P =0.002), currently or previously practicing meditation ( P =0.006 and P =0.0004 respectively), and having a marital status as "single" ( P =0.02). Multivariate regression analysis showed previous meditation practice and a glaucoma diagnosis of <1 year to be predictive of accepting meditation ( P =0.01 and P =0.03 respectively). There were no predictive factors of Perceived Stress Scale scores. CONCLUSION: Given the high acceptance rate of 45-60 minutes daily meditation (63% of glaucoma patients sampled), this may be recommended for the benefit of patients. Patients who have previously meditated, have a relatively new diagnosis of glaucoma, and are single (marital status) were more accepting of meditation practice.

Global Health Partnerships and the Brocher Declaration: Principles for Ethical Short-Term Engagements in Global Health.

Short- term experiences in global health (STEGH), also known as short-term medical missions continue to be a popular mode of engagement in global health activities for students, healthcare providers, and religious groups, driven primarily by organizations from high-income countries. While STEGH have the potential to be beneficial, a large proportion of these do not sustainably benefit the communities they intend to serve, may undermine local health systems, operate without appropriate licenses, go beyond their intended purposes, and may cause harm to patients. With heightened calls to "decolonize" global health, and to achieve ethical, sustainable, and practical engagements, there is a need to establish strong guiding principles for global health engagements. The Advocacy for Global Health Partnerships (AGHP), a multi-sectoral coalition, was established to reflect on and address the concerns relating to STEGH. Towards this end, AGHP created the Brocher Declaration to lay out six main principles that should guide ethical and appropriate STEGH practices. A variety of organizations have accepted the Declaration and are using it to provide guidance for effective implementation of appropriate global health efforts. The Declaration joins broader efforts to promote equity in global health and a critical reevaluation of volunteer-centric, charity-based missions. The current state of the world's health demands a new model of collaboration - one that sparks deep discussions of shared innovation and builds ethical partnerships to address pressing issues in global health.