Attitudes of consultant ophthalmologists in the UK to initial management of glaucoma patients presenting with severe visual field loss: a national survey

BACKGROUND: Recent National Institute of Clinical Excellence guidance suggests primary surgery should be offered to patients presenting with glaucoma with severe visual field loss. We undertook a survey of UK consultant ophthalmologists to determine if this represents current practice and explore attitudes towards managing patients with advanced glaucoma at presentation.

DESIGN: Questionnaire evaluation study.

PARTICIPANTS: All consultant ophthalmologists currently practicing in the UK.

METHODS: A single-page questionnaire was posted to all consultants (n = 910) currently practicing in the UK along with a pre-paid return envelope. A second questionnaire was sent to non-responders (n = 459).

MAIN OUTCOME MEASURES: Questionnaire responses.

RESULTS: 626 responses were received representing 68.8% of the population surveyed. 152 (24%) volunteered a specialist interest in glaucoma. Consensus opinion for both glaucoma specialists (64.9%) and non-glaucoma specialists (62.4%) was to start with primary medical therapy, most commonly citing surgical risk as the primary reason (23% and 22%, respectively) for this approach. Most felt the highest intraocular pressure measurement during follow up (measured in clinic) was the most important variable for prevention of further visual loss (60% of glaucoma specialists and 55% of non-glaucoma specialists). Eighty-three per cent of all responders suggested they would change their practice if evidence supporting primary surgery as a safe and more effective approach existed.

CONCLUSIONS: Recent National Institute of Clinical Excellence guidance does not reflect the current management approach of UK ophthalmologists. The primary concern was related to potential complications of surgery although most practitioners would be willing to change their practice if evidence existed supporting primary surgery in patients presenting with advanced glaucoma.

Control of intraocular pressure after deep sclerectomy

Aim: To study the long-term outcome of deep sclerectomy in patients with open angle glaucoma. Methods: Prospective consecutive series of 43 eyes (38 patients) with medically uncontrolled open-angle glaucoma undergoing deep sclerectomy. All patients underwent clinical assessment before and after surgery at day 7 and at months 1, 3, 6, 12, 18, 24, 36. Surgical success was considered if the patient's intraocular pressure (IOP)>22 mmHg and the IOP was lowered by more than 20% without the use of any medication. Kaplan-Meier survival curves were used to evaluate the success rate. Results: The mean follow-up time was 28.1±8.2 months. Mean IOP decreased significantly from a preoperative value of 24.6±5.5 mmHg to a postoperative value of 18.5±4.6 mmHg at 36 months (P>0.001). Microperforation of TDM occurred in three cases (7.0%) and ciliary body prolapse in one case (2.3%) but did not prevent completion of the operation. Postoperatively, hyphaema was detected in one case and shallow anterior chamber in another case and both were treated conservatively. Bleb encapsulation with elevation of IOP occurred in two cases (4.7%) and was treated with 5-fluorouracil subconjunctival injection. Goniopuncture with neodymium : YAG laser was performed in two cases (4.7%). There were no other late complications with the exception of failure of the operation. On the life-table analysis the success rate at 12, 24, and 30 months were 61.4, 36.6, and 18.9%, respectively. Conclusion: Deep sclerectomy reduced the IOP temporarily while minimising the risk of postoperative complications commonly encountered with standard trabeculectomy. However, after long-term follow-up surgery failed to maintain a low IOP. © 2006 Nature Publishing Group. All rights reserved.

Effects of confining pressure and water content on performance of unsaturated compacted clay under repeated loading

This paper examines the performance of unsaturated soils under repeated loading. As part of the research, a triaxial system was developed that incorporates small-strain measurements using Hall effect transducers, in addition to suction measurements taken using a psychrometer. Tests were conducted on samples of kaolin under constant water mass conditions. The results address the effects of compaction effort and water content at the time of compaction on the overall performance of unsaturated soils, under different amplitudes of loading and different confining pressures. The results show that suction in the sample reduced with increasing number of loading cycles of the same magnitude. The resilient modulus initially increased with increasing water content up to approximately optimum water content, and then reduced substantially with further increase in water content.

The impact of sperm DNA damage in assisted conception and beyond: recent advances in diagnosis and treatment

Abstract Sperm DNA damage is a useful biomarker for male infertility diagnosis and prediction of assisted reproduction outcomes.
It is associated with reduced fertilization rates, embryo quality and pregnancy rates, and higher rates of spontaneous miscarriage
and childhood diseases. This review provides a synopsis of the most recent studies from each of the authors, all of whom have major
track records in the field of sperm DNA damage in the clinical setting. It explores current laboratory tests and the accumulating body
of knowledge concerning the relationship between sperm DNA damage and clinical outcomes. The paper proceeds to discuss the
strengths, weaknesses and clinical applicability of current sperm DNA tests. Next, the biological significance of DNA damage in
the male germ line is considered. Finally, as sperm DNA damage is often the result of oxidative stress in the male reproductive tract,
the potential contribution of antioxidant therapy in the clinical management of this condition is discussed. DNA damage in human spermatozoa is an important attribute of semen quality. It should be part of the clinical work up and properly controlled trials
addressing the effectiveness of antioxidant therapy should be undertaken as a matter of urgency.

Ferroelectric Domain Wall Injection

Ferroelectric domain wall injection has been demonstrated by engineering of the
local electric field, using focused ion beam milled defects in thin single crystal lamellae of KTiOPO4 (KTP). The electric field distribution (top) displays localized field hot-spots, which correlate with nucleation events (bottom). Designed local field variations can also dictate subsequent domain wall mobility, demonstrating a new paradigm in ferroelectric domain wall control.

Irish study on high-density schizophrenia families:field methods and power to detect linkage

Large samples of multiplex pedigrees will probably be needed to detect susceptibility loci for schizophrenia by linkage analysis. Standardized ascertainment of such pedigrees from culturally and ethnically homogeneous populations may improve the probability of detection and replication of linkage. The Irish Study of High-Density Schizophrenia Families (ISHDSF) was formed from standardized ascertainment of multiplex schizophrenia families in 39 psychiatric facilities covering over 90% of the population in Ireland and Northern Ireland. We here describe a phenotypic sample and a subset thereof, the linkage sample. Individuals were included in the phenotypic sample if adequate diagnostic information, based on personal interview and/or hospital record, was available. Only individuals with available DNA were included in the linkage sample. Inclusion of a pedigree into the phenotypic sample required at least two first, second, or third degree relatives with non-affective psychosis (NAP), one whom had schizophrenia (S) or poor-outcome schizo-affective disorder (PO-SAD). Entry into the linkage sample required DNA samples on at least two individuals with NAP, of whom at least one had S or PO-SAD. Affection was defined by narrow, intermediate, and broad criteria. The phenotypic sample contained 277 pedigrees and 1,770 individuals and the linkage sample 265 pedigrees and 1,408 individuals. Using the intermediate definition of affection, the phenotypic sample contained 837 affected individuals and 526 affected sibling pairs. Parallel figures for the linkage sample were 700 and 420. Individuals with schizophrenia from these multiplex pedigrees resembled epidemiologically sampled cases with respect to age at onset, gender distribution, and most clinical symptoms, although they were more thought-disordered and had a poorer outcome. Power analyses based on the model of linkage heterogeneity indicated that the ISHDSF should be able to detect a major locus that influences susceptibility to schizophrenia in as few as 20% of families. Compared to first-degree relatives of epidemiologically sampled schizophrenic probands, first-degree relatives of schizophrenic members from the ISHDSF had a similar risk for schizotypal personality disorder, affective illness, alcoholism, and anxiety disorder. With sufficient resources, large-scale ascertainment of multiplex schizophrenia pedigrees is feasible, especially in countries with catchmented psychiatric care and stable populations. Although somewhat more severely ill, schizophrenic members of such pedigrees appear to clinically resemble typical schizophrenic patients. Our ascertainment process for multiplex schizophrenia families did not select for excess familial risk for affective illness or alcoholism. With its large sample ascertained in a standardized manner from a relatively homogeneous population, the ISHDSF provides considerable power to detect susceptibility loci for schizophrenia.

Comparison of sample preparation methods, validation of an UPLC-MS/MS procedure for the quantification of tetrodotoxin present in marine gastropods and analysis of pufferfish

Tetrodotoxin (TTX) is one of the most potent marine neurotoxins reported. The global distribution of this toxin is spreading with the European Atlantic coastline now being affected. Climate change and increasing pollution have been suggested as underlying causes for this. In the present study, two different sample preparation techniques were used to extract TTX from Trumpet shells and pufferfish samples. Both extraction procedures (accelerated solvent extraction (ASE) and a simple solvent extraction) were shown to provide good recoveries (80-92%). A UPLC-MS/MS method was developed for the analysis of TTX and validated following the guidelines contained in the Commission Decision 2002/657/EC for chemical contaminant analysis. The performance of this procedure was demonstrated to be fit for purpose. This study is the first report on the use of ASE as a mean for TTX extraction, the use of UPLC-MS/MS for TTX analysis, and the validation of this method for TTX in gastropods.

Cold atmospheric pressure plasma jets:Interaction with plasmid DNA and tailored electron heating using dual-frequency excitation

Recent progress in plasma science and technology has enabled the development of a new generation of stable cold non-equilibrium plasmas operating at ambient atmospheric pressure. This opens horizons for new plasma technologies, in particular in the emerging field of plasma medicine. These non-equilibrium plasmas are very efficient sources for energy transport through reactive neutral particles (radicals and metastables), charged particles (ions and electrons), UV radiation, and electro-magnetic fields. The effect of a cold radio frequency-driven atmospheric pressure plasma jet on plasmid DNA has been investigated. The formation of double strand breaks correlates well with the atomic oxygen density. Taken with other measurements, this indicates that neutral components in the jet are effective in inducing double strand breaks. Plasma manipulation techniques for controlled energy delivery are highly desirable. Numerical simulations are employed for detailed investigations of the electron dynamics, which determines the generation of reactive species. New concepts based on nonlinear power dissipation promise superior strategies to control energy transport for tailored technological exploitations. © 2012 American Institute of Physics.

Susceptibility of streptozotocin-induced diabetic rat retinal function and ocular blood flow to acute intraocular pressure challenge.

PURPOSE: To consider whether STZ-induced hyperglycemia renders rat retinal function and ocular blood flow more susceptible to acute intraocular pressure (IOP) challenge.

METHODS: Retinal function (electroretinogram, ERG) was measured during acute IOP challenge (10-100 mmHg, 5 mmHg increments, 3 min/step, vitreal cannulation) in adult Long-Evans rats (6-week old, citrate: n=6, STZ: n=10) 4 weeks after citrate buffer or streptozotocin (STZ, 65 mg/kg, blood glucose > 15 mmol/l) injection. At each IOP, dim and bright flash (-4.56, -1.72 log cd.s.m^-2) ERG responses were recorded to measure inner retinal and ON-bipolar cell function, respectively. Ocular blood flow (laser Doppler flowmetry, citrate; n=6, STZ; n=10) was also measured during acute IOP challenge. Retinae were isolated for qPCR analysis of nitric oxide synthase mRNA expression endothelial, eNos; inducible, iNos; neuronal, nNos).

RESULTS: STZ-induced diabetes increased the susceptibility of inner retinal (IOP at 50% response, 60.1, CI: 57.0-62.0 mmHg vs. citrate: 67.5, CI: 62.1-72.4 mmHg) and ON-bipolar cell function (STZ: 60.3, CI: 58.0-62.8 mmHg vs. citrate: 65.1, CI: 58.0-62.78 mmHg) and ocular blood flow (43.9, CI: 40.8-46.8 vs. citrate: 53.4, CI: 50.7-56.1 mmHg) to IOP challenge. Citrate eyes showed elevated eNos mRNA (+49.7%) after IOP stress, an effect not found in STZ-diabetic eyes (-5.7%, P<0.03). No difference was observed for iNos or nNos (P>0.05) following IOP elevation.

CONCLUSIONS: STZ-induced diabetes increased functional susceptibility during acute IOP challenge. This functional vulnerability is associated with a reduced capacity for diabetic eyes to upregulate eNOS expression and to autoregulate blood flow in response to stress.

Relationship between the magnitude of intraocular pressure during an episode of acute elevation and retinal damage four weeks later in rats

Purpose: To determine relationship between the magnitude of intraocular pressure (IOP) during a fixed-duration episode of acute elevation and the loss of retinal function and structure 4 weeks later in rats.

Methods: Unilateral elevation of IOP (105 minutes) was achieved manometrically in adult Brown Norway rats (9 groups; n = 4 to 8 each, 10–100 mm Hg and sham control). Full-field ERGs were recorded simultaneously from treated and control eyes 4 weeks after IOP elevation. Scotopic ERG stimuli were white flashes (26.04 to 2.72 log cd.s.m^-2). Photopic ERGs were recorded (1.22 to 2.72 log cd.s.m22) after 15 min of light adaptation (150 cd/m2). Relative amplitude (treated/control, %) of ERG components versus IOP was described with a cummulative normal function. Retinal ganglion cell (RGC) layer density was determined post mortem by histology.

Results: All ERG components failed to recover completely normal amplitudes by 4 weeks after the insult if IOP was 70 mmHg or greater during the episode. There was no ERG recovery at all if IOP was 100 mmHg. Outer retinal (photoreceptor) function demonstrated the least sensitivity to prior acute IOP elevation. ERG components reflecting inner retinal function were correlated with post mortem RGC layer density.

Conclusions: Retinal function recovers after IOP normalization, such that it requires a level of acute IOP elevation approximately 10 mmHg higher to cause a pattern of permanent dysfunction similar to that observed during the acute event. There is a ‘threshold’ for permanent retinal functional loss in the rat at an IOP between 60 and 70 mmHg if sustained for 105 minutes or more.

Variation of clinical outcomes used in glaucoma randomised controlled trials:a systematic review

Purpose: In randomised clinical trials (RCTs) the selection of appropriate outcomes is crucial to the assessment of whether one intervention is better than another. The purpose of this review is to identify different clinical outcomes reported in glaucoma trials.

Methods We conducted a systematic review of glaucoma RCTs. A sample or selection of glaucoma trials were included bounded by a time frame (between 2006 and March 2012). Only studies in English language were considered. All clinical measured and reported outcomes were included. The possible variations of clinical outcomes were defined prior to data analysis. Information on reported clinical outcomes was tabulated and analysed using descriptive statistics. Other data recorded included type of intervention and glaucoma, duration of the study, defined primary outcomes, and outcomes used for sample size calculation, if nominated.

Results The search strategy identified 4323 potentially relevant abstracts. There were 315 publications retrieved, of which 233 RCTs were included. A total of 967 clinical measures were reported. There were large variations in the definitions used to describe different outcomes and their measures. Intraocular pressure was the most commonly reported outcome (used in 201 RCTs, 86%) with a total of 422 measures (44%). Safety outcomes were commonly reported in 145 RCTs (62%) whereas visual field outcomes were used in 38 RCTs (16%).

Conclusions There is a large variation in the reporting of clinical outcomes in glaucoma RCTs. This lack of standardisation may impair the ability to evaluate the evidence of glaucoma interventions.

Ionothermal, microwave-assisted synthesis of indium(III) selenide

Microcrystalline indium(III) selenide was prepared from a diphenyl diselenide precursor and a range of chloroindate(III) ionic liquids via a microwave-assisted ionothermal route; this is the first report on the use of either microwave irradiation or ionic liquids to prepare this material. The influence of the reaction temperature, dilution with a spectator ionic liquid and variation of the cation and the anion of the ionic liquid on the product morphology and composition were investigated. This resulted in a time-efficient and facile one-pot reaction to produce microcrystalline indium(III) selenide. The product formation in the ionic liquids has been monitored using Raman spectroscopy. The products have been characterised using PXRD, SEM and EDX. Advantages of this new route, such as the ease of solubilisation of all reactants into one phase at high concentration, the negligible vapour pressure irrespective of the reaction temperature, very fast reaction times, ease of potential scale-up and reproducibility are discussed.

Source depletion and extent of melting in the Tongan sub-arc mantle

The fluid immobile High Field Strength Elements (HFSE) Nb and Ta can be used to distinguish between the effects of variable extents of melting and prior source depletion of the Tongan sub-arc mantle. Melting of spinel Iherzolite beneath the Lau Basin back-arc spreading centres has the ability to fractionate Nb from Ta due to the greater compatibility of the latter in clinopyroxene. The identified spatial variation in plate velocities and separation of melt extraction zones, combined with extremely depleted lavas make Tonga an ideal setting in which to test models for arc melt generation and the role of back-arc magmatism. We present new data acquired by laser ablation-ICPMS of fused sample glasses produced without the use of a melt fluxing agent. The results show an arc trend towards strongly sub-chondritic Nb/Ta (

Sequential injection of domain walls into ferroelectrics at different bias voltages: Paving the way for “domain wall memristors”

Simple meso-scale capacitor structures have been made by incorporating thin (300 nm) single crystal lamellae of KTiOPO4 (KTP) between two coplanar Pt electrodes. The influence that either patterned protrusions in the electrodes or focused ion beam milled holes in the KTP have on the nucleation of reverse domains during switching was mapped using piezoresponse force microscopy imaging. The objective was to assess whether or not variations in the magnitude of field enhancement at localised “hot-spots,” caused by such patterning, could be used to both control the exact locations and bias voltages at which nucleation events occurred. It was found that both the patterning of electrodes and the milling of various hole geometries into the KTP could allow controlled sequential injection of domain wall pairs at different bias voltages; this capability could have implications for the design and operation of domain wall electronic devices, such as memristors, in the future.

Population trapping in bound states during IR-assisted ultrafast photoionization of Ne+

We have investigated the photoionization of Ne+ in the combined field of a short infrared laser pulse and a delayed ultrashort pulse of the infrared laser's 23rd harmonic. We observe an ionization yield compatible with a picture in which one electron gets excited into Rydberg states by the harmonic laser field and is subsequently removed by the infrared laser field. Modulations are seen in the ionization yield as a function of time delay. These modulations originate from the trapping of population in low members of the Rydberg series with different states being populated at different ranges of delay times. The calculations further demonstrate that single-threshold calculations cannot reproduce the Ne+ photoionization yields obtained in multithreshold calculations.