Hindlimb immobilization induces insulin resistance and elevates mitochondrial ROS production in the hippocampus of female rats.

Alzheimer's Disease (AD) is the 5th leading cause of death in older adults and treatment options are severely lacking. Recent findings demonstrate a strong relationship between skeletal muscle and cognitive function, with evidence supporting that muscle quality and cognitive function are positively correlated in older adults. Conversely, decreased muscle function is associated with a 3-fold increased risk of cognitive decline. Based on these observations, the purpose of this study was to investigate the negative effects of muscle disuse (via a model of hindlimb immobilization (HLI)) on hippocampal insulin sensitivity and mitochondrial function and identify the potential mechanisms involved. HLI for 10 days in 4-month-old female Wistar rats resulted in the following novel findings: 1) hippocampal insulin resistance and deficits in whole body glucose homeostasis, 2) dramatically increased mitochondrial reactive oxygen species (ROS) production in the hippocampus, 3) elevated markers for amyloidogenic cleavage of APP and tau protein in the hippocampus, 4) and reduced BDNF expression. These findings were associated with global changes in iron homeostasis, with muscle disuse producing muscle iron accumulation in association with decreased serum and whole brain iron levels. We report the novel finding that muscle disuse alters brain iron homeostasis and reveal a strong negative correlation between muscle and brain iron content. Overall, HLI-induced muscle disuse has robust negative effects on hippocampal insulin sensitivity and ROS production in association with altered brain iron homeostasis. This work provides potential novel mechanisms that may help explain how loss of muscle function contributes to cognitive decline and AD risk.

Prostaglandin FP receptor agonists in the treatment of glaucoma and ocular hypertension: a literature review.

INTRODUCTION: Glaucoma is a leading cause of blindness with intraocular pressure (IOP) as the only known modifiable risk factor. Prostaglandin FP receptor agonists are the first-line medical treatment for glaucoma and ocular hypertension. Despite their efficacy, their IOP lowering effect may be insufficient requiring second agents, and poor patient compliance to medical therapy may preclude their full effect. AREAS COVERED: This literature review examines the novel FP receptor drugs and drug delivery devices in clinical phase trials for treatment of glaucoma. Three novel drugs targeting FP receptors were identified, including latanoprostene bunod, NCX 470, and sepetaprost. Additionally, sustained drug delivery devices in early clinical phase trials included intracameral implants, punctal plugs, ocular rings, and contact lenses. EXPERT OPINION: NO hybrid FP receptor agonists and dual FP/EP3 receptor agonists may show promise as novel medical therapies with greater efficacy than approved prostaglandin analogs in clinical use, with a similar safety profile. Alternatively, drug delivery systems may provide a similar IOP lowering effect to existing agonists but overcome issues with patient compliance and convenience. A personalized approach to drug delivery devices may be required to ensure the most appropriate fit for the patient according to the invasiveness and duration of therapy desired.

Visual Outcomes, Spectacle Independence, and Patient-Reported Satisfaction of the Vivity Extended Range of Vision Intraocular Lens in Patients with Early Glaucoma: An Observational Comparative Study.

Purpose: This study aimed to evaluate and compare visual outcomes, spectacle independence, and patient satisfaction on bilaterally implanted Vivity extended depth-of-focus (EDOF) or monofocal intraocular lenses (IOLs) after cataract surgery in patients with early glaucoma. Patients and Methods: In this retrospective, non-randomized, interventional cohort study, patients with early glaucoma undergoing cataract surgery received bilateral implantation of either EDOF (AcrySof IQ Vivity; Alcon) or monofocal (Clareon/SN6ATx/SN60WF; Alcon) IOLs. The primary outcome was monocular uncorrected intermediate visual acuity (UIVA). The secondary outcomes were monocular uncorrected distance (UDVA) and near (UNVA) visual acuity, spectacle independence, patient satisfaction, and photic phenomena. Fifty-eight eyes from 29 patients, including 32 eyes in the EDOF group and 26 eyes in the monofocal group, were included in the study. Results: UIVA (0.06 ± 0.16 versus 0.39 ± 0.10 LogMAR; P < 0.001) and UNVA outcomes (0.29 ± 0.10 versus 0.55 ± 0.18 LogMAR; P < 0.001) were significantly better in the EDOF group than in the monofocal group, respectively. There was no difference in UDVA and corrected distance visual acuity outcomes between the groups (P > 0.05), but both spectacle independence and patient satisfaction scores were significantly higher in the EDOF group (P < 0.001 and P < 0.05, respectively). There was no difference in self-reported photic phenomena. Conclusion: Bilaterally implanted EDOF IOLs provided excellent distance vision and better intermediate and near vision than monofocal IOLs in patients with early glaucoma. Spectacle independence and patient satisfaction were significantly higher in patients who received EDOF IOLs. Photic phenomena were rare and seldom bothersome.

Selective breeding for physical inactivity produces cognitive deficits via altered hippocampal mitochondrial and synaptic function.

Physical inactivity is the 4th leading cause of death globally and has been shown to significantly increase the risk for developing Alzheimer's Disease (AD). Recent work has demonstrated that exercise prior to breeding produces heritable benefits to the brains of offspring, suggesting that the physical activity status of previous generations could play an important role in one's brain health and their subsequent risk for neurodegenerative diseases. Thus, our study aimed to test the hypothesis that selective breeding for physical inactivity, or for high physical activity, preference produces heritable deficits and enhancements to brain health, respectively. To evaluate this hypothesis, male and female sedentary Low Voluntary Runners (LVR), wild type (WT), and High Voluntary Runner (HVR) rats underwent cognitive behavioral testing, analysis of hippocampal neurogenesis and mitochondrial respiration, and molecular analysis of the dentate gyrus. These analyses revealed that selecting for physical inactivity preference has produced major detriments to cognition, brain mitochondrial respiration, and neurogenesis in female LVR while female HVR display enhancements in brain glucose metabolism and hippocampal size. On the contrary, male LVR and HVR showed very few differences in these parameters relative to WT. Overall, we provide evidence that selective breeding for physical inactivity has a heritable and detrimental effect on brain health and that the female brain appears to be more susceptible to these effects. This emphasizes the importance of remaining physically active as chronic intergenerational physical inactivity likely increases susceptibility to neurodegenerative diseases for both the inactive individual and their offspring.

Transcriptomic analysis reveals novel molecular signaling networks involved in low voluntary running behavior after AP-1 inhibition.

Understanding the neuro-molecular mechanisms that mediate the quantity of daily physical activity (PA) level is of medical significance, given the tremendous health benefits associated with greater physical activity. Here, we examined the effects of intra-nucleus accumbens (NAc) inhibition of activator protein-1 (AP-1), an important transcriptional factor downstream of cAMP response element binding protein (CREB; a reward-related transcriptional regulator), on voluntary wheel running behavior in wild-type (WT) and low voluntary running (LVR) female rats. Transcriptome analysis of the nucleus accumbens (NAc; a brain region critical for PA reward and motivation) was performed to further determine molecular responses to intra-NAc AP-1 inhibition in these rat lines. Within WT rats, intra-NAc AP-1 inhibition caused a significant decrease in overnight running distance in comparison to control rats (p = 0.009). Transcriptomic and bioinformatic analysis in WT rats identified involvement of gene products that regulate cellular proliferation and development, which were cellular processes regulated by AP-1. In contrast to above decreased WT distances, intra-NAc AP-1 inhibition in LVR rats increased nightly running distance in comparison to LVR control rats (p = 0.0008). Further analysis identified gene products that are associated with regulating intracellular Ca2+ homeostasis, calcium ion binding and neuronal excitability. In short, our study aims to gain a comprehensive understanding of transcriptional profile that was due to AP-1 inhibition in NAc, in which it could not only enhance the knowledge regarding molecular regulatory loops within NAc for modulating voluntary running behavior, but also provide further insights into molecular targets for future investigations.

Contributions of physical inactivity and sedentary behavior to metabolic and endocrine diseases.

Physical inactivity is the fourth leading global cause of death and is a major contributor to metabolic and endocrine diseases. In this review we provide a current update of the past 5 years in the field as it pertains to the most prevalent and deadly chronic diseases. Despite the prevalence of physical inactivity in modern society, it remains largely overlooked relative to other comparable risk factors such as obesity, and our molecular understanding of how physical inactivity impacts metabolism is still partially unknown. Therefore, we discuss current clinical inactivity models along with their most recent findings regarding health outcomes along with any discrepancies that are present in the field. Lastly, we discuss future directions and the need for translatable animal models of physical inactivity to discover novel molecular targets for the prevention of chronic disease.

Genetic Testing of Inherited Retinal Disease in Australian Private Tertiary Ophthalmology Practice.

Background: To assess the prevalence of genetic testing for inherited retinal diseases (IRDs) in a tertiary practice setting. Methods: Single-centre retrospective analysis of patients with diagnosed or suspected IRD. Results: Four hundred and sixty-four patient records were analysed. Patients had received care for different IRDs grouped as follows: panretinal pigmentary retinopathies (283, 61%), macular dystrophies (136, 29.3%), stationary diseases (23, 5%), hereditary vitreoretinopathies (14, 3%), and other IRDs (8, 1.7%). The suspected pattern of inheritance of patients' IRD was predominantly autosomal recessive (205, 44.2%). Genetic testing was performed with the corresponding results available for 44 patients (9.5%). Diagnostic yield was 65.9% for the results received. Genetic test results were available mostly for younger patients (13.1% for <45 years vs 6.2% ≥45 years of age, p = 0.01) and those who received greater than 12 months of care (16% for ≥12 months vs 4% for <12 months, p < 0.01). For patients without genetic testing results, reasons include awaiting a geneticist consultation (17.9%), awaiting test results (4.5%), or patient refusal (8.4%). Most clinical records (69.2%) did not document genetic testing status. Conclusion: Genetic testing is increasingly being utilised in the work-up for patients with IRD worldwide. This large Australian private practice IRD cohort shows a low uptake of testing (around 10%), reflecting historical management patterns and accessibility of genetic counselling and testing. The results show that younger patients and those with a longer duration of care were more likely to have received genetic testing. As the importance of IRD genetic testing continues to increase, we expect to see a change in patient management within the Australian private ophthalmology system and testing rates to increase. Further research is required to identify and address clinician and patient barriers to improving genetic testing rates for IRD.

Resistance-exercise training attenuates LPS-induced astrocyte remodeling and neuroinflammatory cytokine expression in female Wistar rats.

Neuroinflammation is an early detectable marker of mild cognitive impairment, the transition state between normal cognition and dementia. Resistance-exercise training can attenuate the cognitive decline observed in patients with mild cognitive impairment. However, the underlying mechanisms of resistance training effects are largely unknown. To further elucidate mechanisms of the known cognitive health benefits from resistance-exercise training, we tested if resistance-exercise training could ameliorate lipopolysaccharide-induced neuroinflammation. Five-week-old female Wistar rats received intracerebroventricular injections of lipopolysaccharides to induce neuroinflammation and cognitive impairment. Rats then underwent 3 wk of progressive ladder climbing to recapitulate resistance-exercise training in humans. Cognition was assessed toward the end of the training period by novelty object recognition testing. Neuroinflammation was measured one and 24 h after the last resistance-exercise training workout. Resistance-exercise training ameliorated cognitive impairment, diminished lipopolysaccharide-induced neuroinflammatory cytokine expression, and attenuated astrocyte remodeling in the dentate gyrus 24 h post exercise. Here, we provide evidence that the ladder-climbing model of resistance-exercise training in rats can improve cognition as early as 3 wk. In addition, these data support the hypothesis that resistance exercise can reduce lipopolysaccharide-induced neuroinflammation in the dentate gyrus.NEW & NOTEWORTHY To further elucidate the known cognitive health benefits from resistance-exercise training, we tested if resistance-exercise training in rats would attenuate lipopolysaccharide-induced neuroinflammation. Our data demonstrated that resistance training had an anti-inflammatory effect in the brain as LPS-induced neuroinflammatory cytokine expression and reactive astrocytic remodeling were reduced in the dentate gyrus after 3 wk of progressive ladder climbing.

Acute Wheel-Running Increases Markers of Stress and Aversion-Related Signaling in the Basolateral Amygdala of Male Rats.

Physical activity (PA) is a non-invasive, cost-effective means of reducing chronic disease. Most US citizens fail to meet PA guidelines, and individuals experiencing chronic stress are less likely to be physically active. To better understand the barriers to maintaining active lifestyles, we sought to determine the extent to which short- versus long-term PA increases stress- and aversion-related markers in wild-type (WT) and low voluntary running (LVR) rats, a unique genetic model of low physical activity motivation. Here, we tested the effects of 1 and 4 weeks of voluntary wheel-running on physiological, behavioral, and molecular measures of stress and Hypothalamic Pituitary Adrenal (HPA)-axis responsiveness (corticosterone levels, adrenal wet weights, and fecal boli counts). We further determined measures of aversion-related signaling (kappa opioid receptor, dynorphin, and corticotropin releasing hormone mRNA expression) in the basolateral amygdala (BLA), a brain region well characterized for its role in anxiety and aversion. Compared to sedentary values, 1, but not 4 weeks of voluntary wheel-running increased adrenal wet weights and plasma corticosterone levels, suggesting that HPA responsiveness normalizes following long-term PA. BLA mRNA expression of prodynorphin (Pdyn) was significantly elevated in WT and LVR rats following 1 week of wheel-running compared to sedentary levels, suggesting that aversion-related signaling is elevated following short- but not long-term wheel-running. In all, it appears that the stress effects of acute PA may increase molecular markers associated with aversion in the BLA, and that LVR rats may be more sensitive to these effects, providing a potential neural mechanism for their low PA motivation.

Creatine Supplementation Upregulates mTORC1 Signaling and Markers of Synaptic Plasticity in the Dentate Gyrus While Ameliorating LPS-Induced Cognitive Impairment in Female Rats.

Mild cognitive impairment (MCI) designates the boundary area between cognitive function in natural aging and dementia, and this is viewed as a therapeutic window to prevent the occurrence of dementia. The current study investigated the neurocognitive effects of oral creatine (Cr) supplementation in young female Wistar rats that received intracerebroventricular injections of lipopolysaccharide (LPS) to mimic MCI. Neuromolecular changes within the dentate gyrus were analyzed following behavioral testing. We also investigated both neurocognitive and neuromolecular changes following Cr supplementation in the absence of LPS in young female Wistar rats to further investigate mechanisms. Interestingly, based on trial 2 of Barnes maze test, Cr supplementation ameliorated spatial learning and memory deficit induced by LPS, shown by decreased latency time and errors to reach the escape box (p < 0.0001, n = 12). Cr supplementation also attenuated recognition memory deficit induced by LPS, shown by increased amount of time taken to explore the new object (p = 0.002, n = 12) during novel object recognition testing. Within the dentate gyrus, Cr supplementation in LPS injected rats upregulated mTORC1 signaling (p = 0.026 for mTOR phosphorylation, p = 0.002 for p70S6K phosphorylation, n = 8) as well as the synapsin (p = 0.008) and PSD-95 synaptic proteins (p = 0.015), in comparisons to LPS injected rats. However, Cr supplementation failed to further enhance spatial memory and recognition memory in the absence of LPS. In conclusion, Cr ameliorates LPS-induced cognitive impairment in a rodent MCI model. Mechanistically, these phenotypic effects may, in part, be mitigated via an upregulation of mTORC1 signaling, and an enhancement in synaptogenesis in the dentate gyrus. While preliminary, these findings may inform future research investigating neurocognitive effects of Cr for MCI patients.

RNA-sequencing and behavioral testing reveals inherited physical inactivity co-selects for anxiogenic behavior without altering depressive-like behavior in Wistar rats.

Physical inactivity is positively associated with anxiety and depression. Considering physical inactivity, anxiety, and depression each have a genetic basis for inheritance, our lab used artificial selectively bred low-voluntary running (LVR) and wild type (WT) female Wistar rats to test if physical inactivity genes selected over multiple generations would lead to an anxiety or depressive-like phenotype. We performed next generation RNA sequencing and immunoblotting on the dentate gyrus to reveal key biological functions from heritable physical inactivity. LVR rats did not display depressive-like behavior. However, LVR rats did display anxiogenic behavior with gene networks associated with reduced neuronal development, proliferation, and function compared to WT counterparts. Additionally, immunoblotting revealed LVR deficits in neuronal development and function. To our knowledge, this is the first study to show that by selectively breeding for physical inactivity genes, anxiety-like genes were co-selected. The study also reveals molecular insights to the genetic influences that physical inactivity has on anxiety-like behavior.

Primary Needling of the Ab Interno Gelatin Microstent Reduces Postoperative Needling and Follow-up Requirements.

PURPOSE: To evaluate the effect of primary needling at the time of ab interno gelatin microstent insertion on postoperative needling rates. DESIGN: Retrospective, interventional cohort study. PARTICIPANTS: Eighty-six eyes of 74 patients with no prior incisional surgery. METHODS: Consecutive eyes with open-angle glaucoma refractory to medical treatment that underwent ab interno gelatin microstent insertion (XEN; Allergan Inc.) with or without primary needling. MAIN OUTCOME MEASURES: Primary outcome measure was the proportion of eyes requiring postoperative needling. Secondary outcome measures included the mean reduction in intraocular pressure (IOP), topical glaucoma medication use, complications, reoperations, and number of follow-up clinic visits over 12 months. RESULTS: Fifty-one eyes (42 patients, median age 74 years) underwent XEN surgery with primary needling at the time of surgery, and 35 eyes (32 patients, median age 73 years) underwent XEN surgery without routine primary needling. Eyes that received routine primary needling had an 84.8% lower rate of postoperative needling (3.9% vs. 25.7%, P = 0.003) and required fewer postoperative clinic visits (P = 0.043). Median IOP was 18.0 mmHg (interquartile range [IQR], 13.0-23.0) on 3.0 (IQR, 2.0-3.0) classes of topical medications at baseline. At 12 months, the median IOP was 11.0 mmHg (IQR, 9.0-14.0) in the primary needling group and 11 mmHg (IQR, 10.0-14.0) when primary needling was not routinely performed. Both groups demonstrated a high safety profile. In total, 5 eyes required further glaucoma surgery with insertion of a glaucoma drainage device. CONCLUSIONS: Primary needling at the time of XEN gel stent insertion is associated with a significant reduction in the need for postoperative needling and postoperative clinic visits. This modification provides a predictable postoperative course with a significant and sustained reduction in both IOP and glaucoma medication requirements with less intense postoperative management.

Standalone iStent Trabecular Micro-bypass Glaucoma Surgery: A Systematic Review and Meta-Analysis.

PRECIS: Standalone trabecular micro-bypass glaucoma surgery with the iStent devices is associated with clinically relevant reductions in intraocular pressure (IOP) sustained over a reasonably long-term while simultaneously reducing medication burden and a relatively favorable safety profile. PURPOSE: While there is a relatively large body of evidence supporting the implantation of the iStent trabecular micro-bypass devices during phacoemulsification in patients with open-angle glaucoma (OAG), its efficacy as a standalone procedure has been less widely reported. The aims of this study were to systematically identify and quantitatively evaluate the efficacy of iStent devices (iStent and iStent inject) when performed independently of cataract surgery in patients with OAG. METHODS: A systematic review of the literature was undertaken in August 2019 to identify studies of standalone trabecular micro-bypass glaucoma surgery with iStent devices in patients with OAG. All randomized trials were considered and nonrandomized studies that included at least 6 months of follow-up or more than 10 eyes. Key efficacy analyses included postoperative IOP and medication use, which were used to evaluate weighted mean differences from baseline, and the proportion of eyes free of ocular medication. Postoperative adverse events were descriptively summarized. RESULTS: A total of 13 studies were identified including 4 randomized controlled trials and 9 nonrandomized or single-arm studies providing data for 778 eyes. In eyes implanted with iStent devices, a weighted mean IOP reduction of 31.1% was observed at 6 to 12 months. In studies reporting longer-term outcomes (36 to 48 mo or 60 mo), the weighted mean IOP reduction was 30.4% and 32.9%, respectively. The pooled weighted mean reduction in IOP from baseline across all studies at 6 to 12 months and 36 to 60 months poststent implantation was 7.01 mm Hg (95% confidence interval: 5.91, 8.11) and 6.59 mm Hg (95% confidence interval: 5.55, 7.63), respectively. Medication burden was reduced by ~1.0 medication at 6 to 18 months and 1.2 medications at 36 to 60 months. Adverse events reported in more than 5% of participants were progression of pre-existing cataract/cataract surgery and loss of best-corrected visual acuity but these rates were no different to those reported in comparator medical therapy study arms. CONCLUSIONS: The results from these studies support the independent effect of the iStent trabecular bypass devices on IOP and medication burden over a duration of follow-up of up to 5 years.

Health economic evaluation in ophthalmology.

Health economic evaluation is the application of economic theories, tools and concepts to healthcare. In the setting of limited resources, increasing demand and a growing array of intervention options, economic evaluation provides a framework for measuring, valuing and comparing the costs and benefits of different healthcare interventions. This review provides an overview of the concepts and methods of economic evaluation, illustrated with examples in ophthalmology. Types of economic evaluation include cost-minimisation, cost-benefit, cost-effectiveness, cost-utility and economic modelling. Topics including utility measures, the quality-adjusted lifeyear, discounting, perspective and timeframe are discussed. Health economic evaluation is important to understand the costs and value of interventions in ophthalmology and to inform health policy as well as guide clinical decision-making.

Occupational therapy for military personnel and military veterans experiencing post-traumatic stress disorder: A scoping review.

INTRODUCTION: As the rate of post-traumatic stress disorder (PTSD) among military personnel and military veterans continues to rise, occupational therapists are increasingly concerned with the impact of this disorder on health, occupational performance, and quality of life. However, the literature on occupational therapy for military personnel and military veterans with PTSD has not been summarised. METHOD: The objective was to identify what is known from the published, peer-reviewed literature, about the services provided by occupational therapists to military personnel and military veterans experiencing PTSD. Arksey and O'Malley's five steps for scoping reviews were utilised. A search of three databases identified 27 articles. RESULTS: Of the 27 papers reviewed, 13 papers discussed military personnel, 13 for military veterans, and 1 reported on both populations. Of these 27, 9 research papers provided data to support the efficacy of interventions, whereas 2 papers reported occupational performance issues. Eight opinion and eight service description papers were included. The most commonly mentioned interventions across the reviewed papers were stress and anger, or coping skills (n = 11), returning to duty (n = 9), physical training (n = 7), and sleep hygiene (n = 6). CONCLUSION: Occupational therapists provide services to military personnel who are vulnerable to PTSD from combat and operational stress. Rarely did publications address intervention efficacy for military personnel. Additionally, there is a paucity of literature that addresses occupational therapy interventions following transition from military service for veterans with PTSD specific to facilitating reintegration to civilian life. Despite this, occupational therapists are well suited to enable military veterans to build upon their existing strengths, skills, and professional identities to minimise the impact of PTSD on daily life and to reach their full potential.

Transnational review of visual standards for driving: How Australia compares with the rest of the world.

IMPORTANCE: Driving is a highly visual task and a primary mode of transportation for many people around the world. BACKGROUND: There appears to be little uniformity of vision standards across the world for driving. We reviewed the basic screening visual requirements for obtaining standard private and commercial driving licences for a total of 70 jurisdictions, and reviewed the evidence behind these standards. DESIGN: Systematic review of basic screening vision standards worldwide for driving and literature review. SAMPLES: Published online documentation on visual acuity and field requirements for driving. METHODS: Journal articles, government reports and websites obtained via a Google search were used to review the regulations for driving. This was limited by the comprehensiveness of resources, and countries were excluded if the requirements were unclear or unattainable. A literature review was performed using Medline with keywords vision, driving and visual field. MAIN OUTCOME MEASURES: Visual parameters used for driving assessment. RESULTS: The results suggest significant variations across the world. The visual acuity requirements for a private licence range from a minimum of 6/9 to 6/60. The minimum binocular horizontal field requirement ranges from 110° to 150°. In general, standards for a commercial licence are stricter compared to a private licence. A literature review could not support the current driving standards as evidence-based. CONCLUSIONS AND RELEVANCE: The disunity of driving vision requirements worldwide likely reflects the inconclusive evidence base. Accounting for individual differences and the ability to predict individual risk is important in the context of determining driving licensure.

Minimally invasive glaucoma surgery: Comparison of iStent with iStent inject in primary open angle glaucoma.

IMPORTANCE: Minimally invasive glaucoma surgery has gained significant traction in recent years. This study evaluates the first- and second-generation trabecular micro-bypass stents "iStent" and "iStent inject". BACKGROUND: To evaluate and compare the effect of a single iStent and double iStent inject in primary open angle glaucoma. DESIGN: Prospective comparative case series. PARTICIPANTS: Primary open angle glaucoma patients undergoing trabecular micro-bypass stent insertion combined with cataract surgery. METHODS: Baseline demographic information, preoperative, intraoperative and postoperative outcomes including intraocular pressure (IOP), visual acuity, reliance on glaucoma medication and complications were collected and analysed. MAIN OUTCOME MEASURES: Primary, secondary and tertiary outcome measures were consecutively defined as an IOP of ≤18 mmHg with zero medications, an IOP of ≤18 mmHg with reduced medications or a 20% reduction in IOP with or without medication. RESULTS: The study comprised 145 eyes in the iStent and 100 eyes in the iStent inject group. At 12 months, 56.0% of the iStent and 51.3% of the iStent inject eyes had achieved primary success and 63.1% and 57.7% secondary success. The mean postoperative IOP was 16.6 mmHg in iStent and 16.9 mmHg in iStent inject. Survival analysis demonstrated a greater incidence of failure in the iStent inject beyond 5 months. CONCLUSIONS AND RELEVANCE: Both trabecular micro-bypass stents in this study were effective in reducing IOP and the burden of medication when combined with cataract surgery. There was no statistically significant difference between the two groups across our outcome measures although the iStent inject required earlier recommencement of medications for optimal IOP control.

Bleb-associated endophthalmitis: Proportion, presentation, management and outcomes in Victoria, Australia.

IMPORTANCE: Bleb-associated endophthalmitis is a potentially vision-threatening complication of trabeculectomy. With improvements in surgical technique and changing patterns of intraoperative antimetabolite use, a re-evaluation of the incidence of bleb-associated endophthalmitis is warranted. BACKGROUND: To investigate changes in the incidence, presentation, management and outcomes of bleb-associated endophthalmitis between 1997 and 2015 in Victoria, Australia. DESIGN: A retrospective cohort analysis. PARTICIPANTS: Consecutive cases of bleb-associated endophthalmitis managed at the Royal Victorian Eye and Ear Hospital (RVEEH) between 1997 and 2015. METHODS: Medical record review of consecutive cases of bleb-associated endophthalmitis and statistical analysis were performed. MAIN OUTCOME MEASURES: Visual acuity, including loss of light perception, intraocular pressure, and need for further surgery. RESULTS: Sixty-seven eyes with bleb-associated endophthalmitis (BAE) were identified. Of these, 41 had trabeculectomy performed in Victoria during the study period, over which time 11 129 trabeculectomies were performed. The proportion of BAE was stable over time (0.4%). The mean age at presentation was 73.7 ± 12.1 years old and the majority of patients were Caucasian (79.1%). The mean duration between glaucoma filtration surgery and the development of bleb-associated endophthalmitis was 3 years (Interquartile Range = 0.4-6.0 years). The cultures were positive in 71.6% of cases. Approximately 1 in 8 patients required enucleation. The final visual acuity was poor with a Snellen Visual Acuity (VA) of 6/60 or worse in two-thirds of patients. CONCLUSIONS AND RELEVANCE: Bleb-associated endophthalmitis is an uncommon complication following glaucoma filtration surgery. The proportion has remained stable over time. Visual outcomes remain poor.

The Safety and Efficacy of Supraciliary Stenting Following Failed Glaucoma Surgery.

PURPOSE: To evaluate the safety and efficacy of supraciliary stenting following failed glaucoma surgery. DESIGN: Interventional case series. METHODS: Setting: Moorfields Eye Hospital, London, United Kingdom. STUDY POPULATION: Twenty eyes from 20 patients with glaucoma refractory to prior glaucoma surgery. INTERVENTION: Ab interno microstent (CyPass Micro-Stent; Alcon, Fort Worth, Texas, USA) implantation into the supraciliary space. MAIN OUTCOME MEASURES: Outcome measures included the occurrence of ocular adverse events, mean intraocular pressure (IOP) change, and glaucoma medication use through 12 months. RESULTS: Mean baseline IOP was 22.5 ± 8.0 mm Hg and number of medications was 2.7 ± 1.0. The majority of patients had undergone either prior trabeculectomy or aqueous shunt surgery. There were no serious intraoperative complications or major adverse events following supraciliary stenting. The most common adverse events included transient hyphema (3/20, 15%), transient IOP > 30 mm Hg (4/20, 20%), and transient IOP < 6 mm Hg (4/20, 20%). At 12 months, mean IOP was 14.9 ± 4.3 mm Hg-a 33.7% reduction (P = .01). Mean medication usage decreased 56% to 1.2 ± 1.5 at 12 months (P = .01). Two patients (10%) required subsequent aqueous shunt insertion. CONCLUSION: Ab interno supraciliary stenting has a favorable safety profile and provides an effective approach to controlling IOP and reducing medication burden in eyes in which previous glaucoma surgery has failed.