Scope of practice of optometrists working in the UK Hospital Eye Service: Second national survey.

PURPOSE: As the landscape in ophthalmology and related commissioning continues to change, there is a pressing need to re-evaluate the current scope of practice of hospital optometrists working within secondary care in the UK. We aim to establish if the skills or services delivered by optometrists have changed to meet varying demands, and to better understand what changes in practice may have arisen as a result of COVID-19. METHOD: A survey developed from that used in 2015 was disseminated to 129 optometry Hospital Eye Service (HES) leads in September 2020, including questions on department workforce; core services; extended roles; procedures undertaken within extended roles; level of autonomy; arrangements for prescribing; training and accreditation, and service changes in response to COVID-19. RESULTS: Ninety responses were received (70% response rate) from within England (76%), Scotland (22%) and Northern Ireland (2%). Whole time equivalents within units ranged from 0.4-79.2 (median of 2.5). In comparison to the 2015 survey, there was an increase in the proportion of units delivering extended roles, with glaucoma (88%) remaining the most common extended role, and new areas of practice in uveitis (21%) and vitreoretinal (13%) services. There was increased use of independent prescribing (67%) in comparison to 18% in 2015 and there was an increase in optometrists delivering laser interventions. In response to COVID-19, optometrists were increasingly delivering telephone consultations and there were new collaborations between primary and secondary care. CONCLUSIONS: Optometrists' scope of practice continues to develop in the HES with an increased variety of roles and an apparent increase in the number of units employing optometrists, often working in roles historically performed by medical practitioners. Such changes appear necessary in recovery and transformation within ophthalmology, alongside wider optometry changes arising at the interface of primary and secondary care.

All-optical reversible control of integrated resonant cavity by a self-assembled azobenzene monolayer.

The next frontier in photonics will rely on the synergistic combination of disparate material systems. One unique organic molecule is azobenzene. This molecule can reversibly change conformations when optically excited in the blue (trans-to-cis) or mid-IR (cis-to-trans). Here, we form an oriented monolayer of azobenzene-containing 4-(4-diethylaminophenylazo)pyridine (Aazo) on SiO2 optical resonators. Due to the uniformity of the Aazo layers, quality factors over 106 are achieved. To control the photo-response, the density of Aazo groups is tuned by integrating methyl spacer molecules. Using a pair of lasers, the molecule is reversibly flipped between molecular conformations, inducing a refractive index change which results in a resonant wavelength shift. The magnitude of the shift scales with the relative surface density of Aazo. To investigate reproducibility and stability of the organic monolayer, three switching cycles are demonstrated, and the performance is consistent even after a device is stored in air for 6 months.

Tetra-Aza-Pentacenes by means of a One-Pot Friedländer Synthesis.

Tetra-aza-pentacenes are attractive n-type small molecules for optoelectronic device applications, yet their syntheses are often laborious. Disclosed here is a one-pot Friedländer synthesis of 1,7,8,14-tetraazapentacece (tAP) derivatives (linear and/or bent), fully aromatized in situ despite the absence of an exogenous oxidant. The photophysics of linear tAPs resembles that of regular pentacene though their crystal structures differ. A LUMO energy of -3.71 eV for di-tert-butylanisole-substituted linear tAP is similar to that of the well-known acceptor, C60 .

Providing capacity in glaucoma care using trained and accredited optometrists: A qualitative evaluation.

INTRODUCTION: The role of optometrists in glaucoma within primary and secondary care has been well described. Whilst many studies examined safety and clinical effectiveness, there is a paucity of qualitative research evaluating enablers and barriers for optometrists delivering glaucoma care. The aims of this study are to investigate qualitatively, and from a multi-stakeholder perspective whether optometric glaucoma care is accepted as an effective alternative to traditional models and what contextual factors impact upon their success. METHODS: Patients were recruited from clinics at Manchester Royal Eye Hospital and nationally via a Glaucoma UK registrant database. Optometrists, ophthalmologists, and other stakeholders involved in glaucoma services were recruited via direct contact and through an optometry educational event. Interviews and focus groups were recorded and transcribed anonymously, then analysed using the framework method and NVivo 12. RESULTS: Interviews and focus groups were conducted with 38 participants including 14 optometrists and 6 ophthalmologists (from all 4 UK nations), and 15 patients and 3 commissioners/other stakeholders. Themes emerging related to: enablers and drivers; challenges and barriers; training; laser; professional practice; the role of other health professionals; commissioning; COVID-19; and patient experience. CONCLUSION: Success in developing glaucoma services with optometrists and other health professionals is reliant on multi-stakeholder input, investment in technology and training, inter-professional respect and appropriate time and funding to set up and deliver services. The multi-stakeholder perspective affirms there is notable support for developing glaucoma services delivered by optometrists in primary and secondary care, with caveats around training, appropriate case selection and clinical responsibility.

Plasma choline concentration varies with different dietary levels of vitamins B6, B12 and folic acid in rats maintained on choline-adequate diets.

Choline is an important component of the human diet and is required for the endogenous synthesis of choline-containing phospholipids, acetylcholine and betaine. Choline can also be synthesised de novo by the sequential methylation of phosphatidylethanolamine to phosphatidylcholine. Vitamins B6, B12 and folate can enhance methylation capacity and therefore could influence choline availability not only by increasing endogenous choline synthesis but also by reducing choline utilisation. In the present experiment, we determined whether combined supplementation of these B vitamins affects plasma choline concentration in a rat model of mild B vitamin deficiency which shows moderate increases in plasma homocysteine. To this end, we measured plasma choline and homocysteine concentrations in rats that had consumed a B vitamin-poor diet for 4 weeks after which they were either continued on the B vitamin-poor diet or switched to a B vitamin-enriched diet for another 4 weeks. Both diets contained recommended amounts of choline. Rats receiving the B vitamin-enriched diet showed higher plasma choline and lower plasma homocysteine concentrations as compared to rats that were continued on the B vitamin-poor diet. These data underline the interdependence between dietary B vitamins and plasma choline concentration, possibly via the combined effects of the three B vitamins on methylation capacity.

Virtual clinics for glaucoma care - Patients' and clinicians' experiences and perceptions: a qualitative evaluation.

BACKGROUND: The role of glaucoma virtual clinics has developed to help meet demand for capacity within busy glaucoma services. There is limited research of patient and clinician experiences and perceptions of these clinics and the aim of this study is to provide further information to help improve patient experience and guide service delivery. METHODS: A mixed methods research design was employed comprising of a patient satisfaction survey, and patient and clinician interviews. Consultant ophthalmologists were recruited from throughout the UK, and patients and data gathering clinical staff recruited from the Manchester Royal Eye Hospital and Bristol Eye Hospital. RESULTS: We received a total of 148 patient satisfaction questionnaires with an overall response rate of 55.4%. Most respondents were diagnosed with primary open angle glaucoma (33.9%) at Manchester and glaucoma suspect status at Bristol (50.6%). Patients had high levels of confidence in the person conducting the tests (94.8% Manchester, 98.8% Bristol), and most were likely to recommend the service to family or friends (94.8% Manchester, 92.6% Bristol). We interviewed 10 consultant ophthalmologists, 10 data gathering staff and 20 patients. A number of key themes emerged from the transcribed interviews including: patient experience, clinician perception of patient experience, service delivery, staffing and staff experience, and patient safety. CONCLUSIONS: Glaucoma virtual clinics can be acceptable to both clinicians and patients, including those with a varied complexity of glaucoma and glaucoma-related disease. Dissatisfaction seemed to relate to poor communication or processes and systems within the service rather than complexity of disease.

Efficacy of a medical food in mild Alzheimer's disease: A randomized, controlled trial.

OBJECTIVE: To investigate the effect of a medical food on cognitive function in people with mild Alzheimer's disease (AD). METHODS: A total of 225 drug-naïve AD patients participated in this randomized, double-blind controlled trial. Patients were randomized to active product, Souvenaid, or a control drink, taken once-daily for 12 weeks. Primary outcome measures were the delayed verbal recall task of the Wechsler Memory Scale-revised, and the 13-item modified Alzheimer's Disease Assessment Scale-cognitive subscale at week 12. RESULTS: At 12 weeks, significant improvement in the delayed verbal recall task was noted in the active group compared with control (P = .021). Modified Alzheimer's Disease Assessment Scale-cognitive subscale and other outcome scores (e.g., Clinician Interview Based Impression of Change plus Caregiver Input, 12-item Neuropsychiatric Inventory, Alzheimer's disease Co-operative Study-Activities of Daily Living, Quality of Life in Alzheimer's Disease) were unchanged. The control group neither deteriorated nor improved. Compliance was excellent (95%) and the product was well tolerated. CONCLUSIONS: Supplementation with a medical food including phosphatide precursors and cofactors for 12 weeks improved memory (delayed verbal recall) in mild AD patients. This proof-of-concept study justifies further clinical trials.

Care pathways for glaucoma detection and monitoring in the UK.

Glaucoma presents considerable challenges in providing clinically and cost-effective care pathways. While UK population screening is not seen as justifiable, arrangements for case finding have historically been considered relatively ineffective. Detection challenges include an undetected disease burden, whether from populations failing to access services or difficulties in delivering effective case-finding strategies, and a high false positive rate from referrals via traditional case finding pathways. The enhanced General Ophthalmic Service (GOS) in Scotland and locally commissioned glaucoma referral filtering services (GRFS) elsewhere have undoubtedly reduced false positive referrals, and there is emerging evidence of effectiveness of these pathways. At the same time, it is recognised that implementing GRFS does not intrinsically reduce the burden of undetected glaucoma and late presentation, and obvious challenges remain. In terms of diagnosis and monitoring, considerable growth in capacity remains essential, and non-medical health care professional (HCP) co-management and virtual clinics continue to be important solutions in offering requisite capacity. National guidelines, commissioning recommendations, and the Common Clinical Competency Framework have clarified requirements for such services, including recommendations on training and accreditation of HCPs. At the same time, the nature of consultant-delivered care and expectations on the glaucoma specialist's role has evolved alongside these developments. Despite progress in recent decades, given projected capacity requirements, further care pathways innovations appear mandated. While the timeline for implementing potential artificial intelligence innovations in streamlining care pathways is far from established, the glaucoma burden presents an expectation that such developments will need to be at the vanguard of future developments.

Rapid Multiscale Computational Screening for OLED Host Materials.

The design of new host materials for phosphorescent organic light emitting diodes (OLEDs) is challenging because several physical property requirements must be met simultaneously. A triplet energy ( ET) higher than that of the chosen emitting dopant, appropriate highest occupied molecular orbital/lowest unoccupied molecular orbital energy levels, good charge carrier transport, and high stability are all required. Here, computational methods were used to screen structures to find the most promising candidates for OLED hosts. The screening was carried out in three Tiers. The Tier 1 selection, based on density functional theory calculations, identified a set of eight molecular structures with ET > 2.9 eV, suitable for hosting blue phosphorescent dopants such as iridium(III)bis((4,6-di-fluorophenyl)-pyridinato-N,C2')picolinate. Phenanthro[9,10- d]imidazole was chosen as the starting point for the Tier 2 selection. Thirty-seven unique molecular structures were enumerated by isoelectronic nitrogen transmutation of up to two CH fragments of the phenanthrene. Three molecules, that is, imidazo[4,5- f]-phenanthrolines with nitrogens at the 1,10-, 3,8-, and 4,7-positions, were selected for Tier 3, which involved the use of molecular dynamics simulations and electron coupling calculations to predict differences in charge transport between the three materials. The three were explored experimentally through synthesis and device fabrication. The singlet, triplet, and frontier orbital energies computed using single-molecule density functional theory calculations ( Tiers 1 and 2) were consistent with the experimental values in a fluid solution, and the multiscale modeling scheme ( Tier 3) correctly predicted the poor device performance of one material. We conclude that screening host materials using only single-molecule quantum mechanical data was not sufficient to predict whether a given material would make a good OLED host with certainty; however, they can be used to screen out materials that are destined to fail due to low singlet/triplet energies or a poor match of the frontier orbital energies to the dopant or transport materials.

Clinical effectiveness of the Manchester Glaucoma Enhanced Referral Scheme.

BACKGROUND: Glaucoma referral filtering schemes have operated in the UK for many years. However, there is a paucity of data on the false-negative (FN) rate. This study evaluated the clinical effectiveness of the Manchester Glaucoma Enhanced Referral Scheme (GERS), estimating both the false-positive (FP) and FN rates. METHOD: Outcome data were collected for patients newly referred through GERS and assessed in 'usual-care' clinics to determine the FP rate (referred patients subsequently discharged at their first visit). For the FN rate, glaucoma suspects deemed not requiring referral following GERS assessment were invited to attend for a 'reference standard' examination including all elements of assessment recommended by National Institute for Health and Care Excellence (NICE) by a glaucoma specialist optometrist. A separate 33 cases comprising randomly selected referred and non-referred cases were reviewed independently by two glaucoma specialist consultant ophthalmologists to validate the reference standard assessment. RESULTS: 1404 patients were evaluated in GERS during the study period; 651 (46.3%) were referred to the Hospital Eye Service (HES) and 753 (53.6%) were discharged. The FP rate in 307 assessable patients referred to the HES was 15.5%. This study reviewed 131 (17.4%) of those patients not referred to the HES through the GERS scheme; 117 (89.3%) were confirmed as not requiring hospital follow-up; 14 (10.7%) required follow-up, including 5 (3.8%) offered treatment. Only one patient (0.8%) in this sample met the GERS referral criteria and was not referred (true FN). There were no cases of missed glaucoma or non-glaucomatous pathology identified within our sample. CONCLUSION: The Manchester GERS is an effective glaucoma filtering scheme with a low FP and FN rate.

Systematic Control of the Orientation of Organic Phosphorescent Pt Complexes in Thin Films for Increased Optical Outcoupling.

Orienting light-emitting molecules relative to the substrate is an effective method to enhance the optical outcoupling of organic light-emitting devices. Platinum(II) phosphorescent complexes enable facile control of the molecular alignment due to their planar structures. Here, the orientation of Pt(II) complexes during the growth of emissive layers is controlled by two different methods: modifying the molecular structure and using structural templating. Molecules whose structures are modified by adjusting the diketonate ligand of the Pt complex, dibenzo-(f,h)quinoxaline Pt dipivaloylmethane, (dbx)Pt(dpm), show an ≈20% increased fraction of horizontally aligned transition dipole moments compared to (dbx)Pt(dpm) doped into a 4,4'-bis(N-carbazolyl)-1,1'-biphenyl, CBP, host. Alternatively, a template composed of highly ordered 3,4,9,10-perylenetetracarboxylic dianhydride monolayers is predeposited to drive the alignment of a subsequently deposited emissive layer comprising (2,3,7,8,12,13,17,18-octaethyl)-21H,23H-porphyrinplatinum(II) doped into triindolotriazine. This results in a 60% increase in horizontally aligned transition dipole moments compared to the film deposited in the absence of the template. The findings provide a systematic route for controlling molecular alignment during layer growth, and ultimately to increase the optical outcoupling in organic light-emitting diodes.

The potential role of nutritional components in the management of Alzheimer's Disease.

Epidemiological evidence linking nutrition to the incidence and risk of Alzheimer Disease is rapidly increasing. The specific nutritional deficiencies in Alzheimer patients may suggest a relative shortage of specific macro- and micronutrients. These include omega-3 fatty acids, several B-vitamins and antioxidants such as vitamins E and C. Recent mechanistic studies in cell systems and animal models also support the idea that nutritional components are able to counteract specific aspects of the neurodegenerative and pathological processes in the brain. In addition, it has been shown that several nutritional components can also effectively stimulate membrane formation and synapse formation as well as improve behavior and cerebrovascular health. The suggested synergy between nutritional components to improve neuronal plasticity and function is supported by epidemiological studies as well as experimental studies in animal models. The ability of nutritional compositions to stimulate synapse formation and effectively reduce Alzheimer Disease neuropathology in these preclinical models provides a solid basis to predict potential to modify the disease process, especially during the early phases of Alzheimer Disease.

Acceptability and use of glaucoma virtual clinics in the UK: a national survey of clinical leads.

OBJECTIVE: The purpose of this paper is to describe the findings of a national survey that aimed to estimate the proportion of Hospital Eye Service (HES) units using glaucoma virtual clinics, to determine how these services differ and to gauge clinicians' views and opinions on the safety and acceptability of this model of care compared with usual care. METHODS AND ANALYSIS: This 12-question survey was disseminated nationally to 92 clinical lead consultant ophthalmologists using SurveyMonkey. RESULTS: The response rate was 45.7%. There were 21 out of the total 42 respondents (50.0%) who were based at an NHS Trust where glaucoma virtual clinics were already being used and a further 9 (21.4%) were planning to establish one. Clinical leads largely rated efficiency and patient safety to be at least equivalent to usual care (92.9%) and 81.0% perceived glaucoma virtual clinics to be acceptable to patients. The main reasons for not running glaucoma virtual clinics were insufficient staff (71.4%) and inadequate space (47.6%). The majority of those running virtual clinics used this model of care for 'lower risk' patients such as ocular hypertensives (90.5%) and glaucoma suspects. CONCLUSION: Glaucoma virtual clinics are employed by a large proportion of HES units, with many seeking to develop such services. Clinical leads largely rate efficiency, patient safety and the perception of patient acceptability to be at least equivalent to usual care.

Gram Scale Synthesis of Benzophenanthroline and Its Blue Phosphorescent Platinum Complex.

The design, synthesis, and characterization of 12-phenylbenzo[f][1,7]phenanthroline, Bzp, is reported. Its use as a fluorine-free ligand for sky blue phosphorescence is demonstrated in a cyclometalated platinum complex, BzpPtDpm. BzpPtDpm phosphoresces at the same wavelength as its analogous 4,6-difluorophenylpyridine complex at both room temperature (466 nm) and 77 K (458 nm). Finally, production of a conformationally restricted derivative of BzpPtDpm with greatly increased quantum yield (46%) validates the versatility of the synthetic route.

Cyclic GMP-dependent and cyclic AMP-dependent protein kinases, protein kinase modulators and phosphodiesterases in arteries and veins of dogs. Distribution and effects of arteriovenous fistula and arterial occlusion.

Possible involvement of cyclic GMP-dependent and cyclic AMP-dependent protein kinases, protein kinase modulators and cyclic nucleotide phosphodiesterases in functions of vascular tissues were investigated in the dog. All of the above activities, localized in the smooth muscle-rich inner layer of the blood vessels, were found to be higher in the arteries than in the veins. The peripheral arteries were disproportionately richer in cyclic GMP-dependent protein kinase (as indicated by high ratios of cyclic GMP-dependent to cyclic AMP-dependent protein kinase) than were the veins, with the exception of the pulmonary artery, an atypical arterial tissue exposed to low blood pressure. Interestingly, the protein kinase ratio for the aorta, an artery with no significant role in blood pressure regulation, was not higher than that for the vena cava. Creation of femoral arteriovenous fistulae in the dogs led to preferential reductions in the cyclic GMP-dependent enzyme activity both in the proximal and distal arteries, whereas it was elevated in the stressed vein distal to the anastomotic site. The cyclic GMP-dependent enzyme was preferentially reduced in the saphenous artery distal to occlusion. Changes in the cyclic GMP-dependent enzyme activity appeared to precede gross atrophy or hypertrophy of the vessels. It is suggested that the vascular cyclic GMP-dependent protein kinase may be closely related to peripheral resistance and its regulation.

Long-lasting effects of neonatal dexamethasone treatment on spatial learning and hippocampal synaptic plasticity: involvement of the NMDA receptor complex.

The effects of neonatal dexamethasone (DEX) treatment on spatial learning and hippocampal synaptic plasticity were investigated in adult rats. Spatial learning in reference and working memory versions of the Morris maze was impaired in DEX-treated rats. In hippocampal slices of DEX rats, long-term depression was facilitated and potentiation was impaired. Paired-pulse facilitation was normal, suggesting a postsynaptic defect as cause of the learning and plasticity deficits. Western blot analysis of hippocampal postsynaptic densities (PSD) revealed a reduction in NR2B subunit protein, whereas the abundance of the other major N-methyl-D-aspartate (NMDA) receptor subunits (NR1, NR2A), AMPA receptor subunits (GluR2/3), scaffolding proteins, and Ca2+/calmodulin-dependent protein kinase II (alphaCaMKII) were unaltered. This selective reduction in NR2B likely resulted from altered receptor assembly rather than subunit expression, because the abundance of NR2B in the homogenate and crude synaptosomal fractions was unaltered. In addition, the activity of alphaCaMKII, an NMDA receptor complex associated protein kinase, was increased in PSD of DEX rats. The results indicate that neonatal treatment with DEX causes alterations in composition and function of the hippocampal NMDA receptor complex that persist into adulthood. These alterations likely explain the deficits in hippocampal synaptic plasticity and spatial learning induced by neonatal DEX treatment.

Pregnancy diabetes: A comparison of diagnostic protocols based on point-of-care, routine and optimized laboratory conditions.

In vitro glycolysis poses a problem during diabetes screening, especially in remote laboratories. Point-of-care analysis (POC) may provide an alternative. We compared POC, routine and STAT analysis and a feasible protocol during glucose tolerance test (GTT) for pregnancy diabetes (GDM) screening. In the routine protocol, heparin tubes were used and turn-around-time (TAT) was unsupervised. In the STAT protocol, tubes were processed immediately. The feasible protocol comprised of citrated tubes with a TAT of 1 hour. Outcome was defined as glucose concentration and clinical diagnosis. Glucose measured by POC was higher compared to routine analysis at t = 0 (0.25 mM) and t = 120 (1.17 mM) resulting in 17% more GDM diagnoses. Compared to STAT analysis, POC glucose was also higher, although less pronounced (0.06 and 0.9 mM at t = 0 and t = 120 minutes, respectively) and misclassification was only 2%. Glucose levels and clinical diagnosis were similar using the feasible protocol and STAT analysis (0.03 mM and -0.07 mM at t = 0 and t = 120, 100% identical diagnoses). POC is an viable alternative for STAT glucose analysis in GDM screening (sensitivity: 100%, specificity: 98%). A feasible protocol (citrated phlebotomy tubes with a TAT of 60 minutes) resulted in 100% identical outcome and provides the best alternative.

Tolerability and safety of Souvenaid in patients with mild Alzheimer's disease: results of multi-center, 24-week, open-label extension study.

BACKGROUND: The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to improve synapse formation and function in patients with Alzheimer's disease (AD). Two double-blind randomized controlled trials (RCT) with Souvenaid of 12 and 24 week duration (Souvenir I and Souvenir II) showed that memory performance was improved in drug-naïve mild AD patients, whereas no effects on cognition were observed in a 24-week RCT (S-Connect) in mild to moderate AD patients using AD medication. Souvenaid was well-tolerated in all RCTs. OBJECTIVE: In this 24-week open-label extension (OLE) study to the 24-week Souvenir II RCT, long-term safety and intake adherence of the medical food Souvenaid was evaluated. METHODS: Patients with mild AD (n = 201) received Souvenaid once-daily during the OLE. Main outcome parameters were safety and product intake adherence. The memory domain z-score from a revised neuropsychological test battery was continued as exploratory parameter. RESULTS: Compared to the RCT, a similar (low) incidence and type of adverse events was observed, being mainly (68.3%) of mild intensity. Pooled data (RCT and OLE) showed that 48-week use of Souvenaid was well tolerated with high intake adherence (96.1%). Furthermore, a significant increase in the exploratory memory outcome was observed in both the active-active and control-active groups during Souvenaid intervention. CONCLUSION: Souvenaid use for up to 48-weeks was well tolerated with a favorable safety profile and high intake adherence. The findings in this OLE study warrant further investigation toward the long-term safety and efficacy of Souvenaid in a well-controlled, double-blind RCT.