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Biomedical subjects

Sarah L Hosking

Publications and source records attributed to Sarah L Hosking.

15 recordsLinked to original sources

Operator-induced errors in Hartmann-Shack wavefront sensing: model eye study.

PURPOSE: To evaluate the effects of instrument realignment and angular misalignment during the clinical determination of wavefront aberrations by simulation in model eyes. SETTING: Aston Academy of Life Sciences, Aston University, Birmingham, United Kingdom. METHODS: Six model eyes were examined with wavefront-aberration-supported cornea ablation (WASCA) (Carl Zeiss Meditec) in 4 sessions of 10 measurements each: sessions 1 and 2, consecutive repeated measures without realignment; session 3, realignment of the instrument between readings; session 4, measurements without realignment but with the model eye shifted 6 degrees angularly. Intersession repeatability and the effects of realignment and misalignment were obtained by comparing the measurements in the various sessions for coma, spherical aberration, and higher-order aberrations (HOAs). RESULTS: The mean differences between the 2 sessions without realignment of the instrument were 0.020 microm +/- 0.076 (SD) for Z(3)(-1)(P = .551), 0.009 +/- 0.139 microm for Z(3)(1)(P = .877), 0.004 +/- 0.037 microm for Z(4)(0) (P = .820), and 0.005 +/- 0.01 microm for HO root mean square (RMS) (P = .301). Differences between the nonrealigned and realigned instruments were -0.017 +/- 0.026 microm for Z(3)(-1)(P = .159), 0.009 +/- 0.028 microm for Z(3)(1) (P = .475), 0.007 +/- 0.014 microm for Z(4)(0)(P = .296), and 0.002 +/- 0.007 microm for HO RMS (P = 0.529; differences between centered and misaligned instruments were -0.355 +/- 0.149 microm for Z(3)(-1) (P = .002), 0.007 +/- 0.034 microm for Z(3)(1)(P = .620), -0.005 +/- 0.081 microm for Z(4)(0)(P = .885), and 0.012 +/- 0.020 microm for HO RMS (P = .195). Realignment increased the standard deviation by a factor of 3 compared with the first session without realignment. CONCLUSIONS: Repeatability of the WASCA was excellent in all situations tested. Realignment substantially increased the variance of the measurements. Angular misalignment can result in significant errors, particularly in the determination of coma. These findings are important when assessing highly aberrated eyes during follow-up or before surgery.

Calibration↗

Non-invasive vascular impedance measures demonstrate ocular vasoconstriction during isometric exercise.

AIMS: The calculation of impedance for a vascular network is a common method used in circulation studies. Impedance indices (the ratios of the harmonics of pressure to the harmonics of flow) provide the investigator with a measure of the opposition to blood flow in a pulsatile system and are a proven indicator for vasculopathy. Previous studies investigating the eye's opposition to blood flow have concentrated on simple measures of resistance (the ratio of mean pressure difference to mean flow) which are more appropriate to a steady state or non-pulsatile system. The purpose of this study is to demonstrate a new, non-invasive, method to determine the vascular impedance of the eye during the known physiologic stress of sustained isometric exercise. METHODS: Waveforms of ocular blood flow and carotid arterial blood pressure were measured non-invasively. Ocular blood flow waveforms were calculated using the Langham-Silver method by measuring the small fluctuations in intraocular pressure intraocular pressure over time with a high fidelity pneumatonometer. Carotid arterial blood pressure waveforms were determined using a SphygmoCor electronic tonometer held over the common carotid artery of the neck. Both waveforms were recorded simultaneously in normal volunteers under two conditions: (1) a baseline resting state and (2) during sustained isometric exercise. The components of the two waveforms (the harmonics) were calculated using a Fast Fourier transform and expressed as a ratio in order to determine a set of impedance values for each condition. The first four impedance values were calculated. RESULTS: 12 volunteers (six male: six female) with a mean age of 27 years (range 22-32 years) were recruited to the study. In comparison to baseline resting conditions, mean carotid blood pressure and heart rate both increased significantly during exercise: baseline mean carotid blood pressure, 82.6+/-8.2 mm Hg vs exercise mean carotid blood pressure, 93.8+/-12.8 mm Hg (p<0.001); baseline pulse rate, 64.6+/-9.1 BP(m) vs exercise pulse rate, 71.8+/-9.7 BP(m) (p<0.001). Compared to resting conditions, the first and third impedance values demonstrated significant change during exercise: the first impedance value rose (83.9+/-25.6 mm Hg-s/microl to 117.1 +/- 40.9 mm Hg-s/microl, p = 0.01) and the third impedance value fell (487.9 +/- 294.7 mm Hg-s/microl to 248.3+/-206.8 mm Hg-s/microl, p = 0.01). CONCLUSIONS: The present study demonstrates, for the first time, a practical non-invasive method of calculating an index of impedance moduli for the pulsatile quotient of blood flow to the eye. Furthermore, during controlled isometric exercise, the impedance moduli displayed changes consistent with that known for a vascular system during vasoconstriction. The calculation of impedance moduli for the eye therefore shows promise for future investigations into ocular conditions where vascular obstruction is an aetiological factor.

Adult↗

Wavefront analyzers induce instrument myopia.

PURPOSE: To assess the accuracy of three wavefront analyzers versus a validated binocular open-view autorefractor in determining refractive error in non-cycloplegic eyes. METHODS: Eighty eyes were examined using the SRW-5000 open-view infrared autorefractor and, in randomized sequence, three wavefront analyzers: 1) OPD-Scan (NIDEK, Gamagori, Japan), 2) WASCA (Zeiss/Meditec, Jena, Germany), and 3) Allegretto (WaveLight Laser Technologies AG, Erlangen, Germany). Subjects were healthy adults (19 men and 21 women; mean age: 20.8 +/- 2.5 years). Refractive errors ranged from +1.5 to -9.75 diopters (D) (mean: +1.83 +/- 2.74 D) with up to 1.75 D cylinder (mean: 0.58 +/- 0.53 D). Three readings were collected per instrument by one examiner without anticholinergic agents. Refraction values were decomposed into vector components for analysis, resulting in mean spherical equivalent refraction (M) and J0 and J45 being vectors of cylindrical power at 0 degrees and 45 degrees, respectively. RESULTS: Positive correlation was observed between wavefront analyzers and the SRW-5000 for spherical equivalent refraction (OPD-Scan, r=0.959, P<.001; WASCA, r=0.981, P<.001; Allegretto, r=0.942, P<.001). Mean differences and limits of agreement showed more negative spherical equivalent refraction with wavefront analyzers (OPD-Scan, 0.406 +/- 0.768 D [range: 0.235 to 0.580 D] [P<.001]; WASCA, 0.511 +/- 0.550 D [range: 0.390 to 0.634 D] [P<.001]; and Allegretto, 0.434 +/- 0.904 D [range: 0.233 to 0.635 D] [P<.001]). A second analysis eliminating outliers showed the same trend but lower differences: OPD-Scan (n=75), 0.24 +/- 0.41 D (range: 0.15 to 0.34 D) (P<.001); WASCA (n=78), 0.46 +/- 0.47 D (range: 0.36 to 0.57 D) (P<.001); and Allegretto (n=77), 0.30 +/- 0.62 D (range: 0.16 to 0.44 D) (P<.001). No statistically significant differences were noted for J0 and J45. CONCLUSIONS: Wavefront analyzer refraction resulted in 0.30 D more myopia compared to SRW-5000 refraction in eyes without cycloplegia. This is the result of the accommodation excess attributable to instrument myopia. For the relatively low degrees of astigmatism in this study (<2.0 D), good agreement was noted between wavefront analyzers and the SRW-5000.

Adult↗

Aviation-related respiratory gas disturbances affect dark adaptation: a reappraisal.

This study examined the time course of early scotopic threshold sensitivity during dark adaptation under mild to moderate hypoxia, moderate hypocapnia and hyperoxia, measuring detection time displacement relative to normoxia. Cone rod inflection and early rod adaptation were highlighted using progressively dimmer green flash stimuli. Early scotopic sensitivity was significantly delayed by hypoxia and hastened by hypocapnia and hyperoxia. Effects of respiratory disturbance on dark adaptation include temporal shifts of early scotopic sensitivity while human rod photoreceptors appear functionally hypoxic when breathing air at one atmosphere. At night, supplementary oxygen may benefit aircrew visual sensitivity, even at ground level.

Adult↗

The effect of antiepileptic drugs on visual performance.

Visual disturbances are a common side-effect of many antiepileptic drugs. Non-specific retino- and neurotoxic visual abnormalities, that are often reported with over-dosage and prolonged AED use, include diplopia, blurred vision and nystagmus. Some anticonvulsants are associated with specific visual problems that may be related to the mechanistic properties of the drug, and occur even when the drugs are administered within the recommended daily dose. Vigabatrin, a GABA-transaminase inhibitor, has been associated with bilateral concentric visual field loss, electrophysiological changes, central visual function deficits including reduced contrast sensitivity and abnormal colour perception, and morphological alterations of the fundus and retina. Topiramate, a drug that enhances GABAergic transmission, has been associated with cases of acute closed angle glaucoma, while tiagabine, a GABA uptake inhibitor, has been investigated for a potential GABAergic effect on the visual field. Only mild neurotoxic effects have been identified for patients treated with gabapentin, a drug designed as a cyclic analogue of GABA but exhibiting an unknown mechanism while carbamazepine, an inhibitor of voltage-dependent sodium channels, has been linked with abnormal colour perception and reduced contrast sensitivity. The following review outlines the visual disturbances associated with some of the most commonly prescribed anticonvulsants. For each drug, the ocular site of potential damage and the likely mechanism responsible for the adverse visual effects is described.

Anticonvulsants↗

Regional variability in visual field sensitivity during hypercapnia.

PURPOSE: Previous investigations have demonstrated a relative vascular autoregulatory inefficiency of the inferior compared to the superior retina in healthy subjects breathing increased CO(2). The purpose of this study was to determine whether the superior and inferior visual field sensitivities of healthy eyes are similarly affected during mild hypercapnia. DESIGN: Experimental study. METHODS: Visual field analysis (Humphrey Field Analyser; SITA standard 24-2 program) was carried out on one randomly selected eye of 22 subjects (mean age, 27.7 +/- 5 years) during normal room air breathing and isoxic hypercapnia. The Student paired t-tests were used to compare the visual field indices mean deviation (MD) and pattern standard deviation (PSD) for each breathing condition. A secondary, sectoral analysis of mean pointwise sensitivity was performed for each condition. In each case a P value of <.01 was considered statistically significant (Bonferroni corrected). RESULTS: Visual field MD was -0.23 +/- 0.95dB during room air breathing and -0.49 +/- 1.04dB during hypercapnia (P =.034). Sectoral pointwise mean sensitivity deteriorated by 0.46dB (P =.006) in the upper visual hemifield during hypercapnia, whereas no significant difference was observed for the lower hemifield (P =.331). CONCLUSIONS: The upper visual hemifield exhibited a significantly greater degree of deterioration in pointwise visual field mean sensitivity compared to the lower hemifield during hypercapnic conditions. This suggests that the upper visual hemifield and hence inferior retina is more susceptible to insult during hypercapnia than the superior retina in healthy individuals. A regional susceptibility of inferior retinal function to altered vascular or metabolic effects may account for the earlier and more frequent inferior nerve fibre damage associated with glaucomatous optic neuropathy.

Adult↗

Spectral content of the intraocular pressure pulse wave: glaucoma patients versus normal subjects.

BACKGROUND: Many studies have found that the intraocular pressure (IOP) is lower in glaucomatous populations than in normal groups. An alternative method of analysis, commonly used in the investigation of arterial blood pressure, is to reduce the pulse waveform to its component Fourier parts. The purpose of this study, therefore, was to determine whether such a technique is applicable to the IOP pulse and to investigate whether it was superior at differentiating diseased from healthy eyes. METHODS: Using a pneumatonometer, continuous 10-s IOP recordings were taken from 10 glaucoma patients and 10 normal subjects. The IOP recordings were then analysed using the fast Fourier transform (FFT) to determine their spectral components. In addition, standard IOP parameters (pulse amplitude, pulse volume, and pulsatile ocular blood flow) were measured to allow comparison with the waveform analysis technique. RESULTS: Analysis by FFT successfully determined the IOP pulse's higher spectral components up to the fourth harmonic. In addition, although standard measurements of the IOP pulse (such as pulse amplitude) were insignificant, the second ( P=0.034), third ( P=0.015) and fourth ( P=0.013) harmonics of the waveform successfully differentiated between the glaucoma and normal groups. CONCLUSION: Spectral analysis of the IOP pulse appears to be a promising technique in the investigation of ocular vascular disease.

Blood Pressure↗

Neurotoxic effects of GABA-transaminase inhibitors in the treatment of epilepsy: ocular perfusion and visual performance.

Vigabatrin is a GABA (gamma-aminobutyric acid) transaminase inhibitor that elicits an antiepileptic effect by enhancing inhibitory neurotransmission in the brain. Vigabatrin has been previously associated with concentric peripheral visual field loss and visual electrophysiological abnormalities. Recently, visual function deficits of the central retina have been identified in a proportion of patients receiving vigabatrin; these include disturbances in colour perception, contrast sensitivity and short-wavelength automated perimetry. Consequently, it is suggested that vigabatrin-associated retinal toxicity is diffuse inducing subtle central visual dysfunction and more severe peripheral visual defects. Reductions in cerebral blood flow and cerebral metabolic rate for glucose occur in epilepsy patients receiving antiepileptic drug therapy. Despite the known cerebral haemodynamic alterations in epilepsy and the visual consequences of vigabatrin therapy, ocular blood flow has only recently been investigated in this group. We present findings from a series of novel investigations that identify compromised retinal microvascular perfusion and pulsatile ocular blood flow (POBF) in epilepsy patients. The reduction in POBF was exacerbated in epilepsy patients treated with vigabatrin compared to conventionally treated epilepsy patients. A number of theories are presented to explain compromised ocular blood flow in vigabatrin treated epilepsy patients, and the possibility of a GABAergic mechanism of toxicity is discussed.

4-Aminobutyrate Transaminase↗

Patients treated with vigabatrin exhibit central visual function loss.

PURPOSE: To investigate visual function in the central 10 degrees in patients who have undergone vigabatrin (VGB) antiepileptic drug (AED) therapy with the aim of identifying a clinical regimen for assessing central visual function. METHODS: The sample comprised 12 epilepsy patients (mean age, 38.6 +/- 11.7 years) who had been treated with VGB (either as monotherapy or polytherapy). A number of central visual-function tests were carried out for each eye, including high-contrast LogMAR visual acuity, short-wavelength automated perimetry (SWAP 10-2), spatial contrast sensitivity (CSV-1000), and Farnsworth-Munsell (FM) 100-hue colour discrimination. RESULTS: The group mean cumulative VGB dose was 5,086 +/- 3,245 g. The average SWAP 10-2 mean deviation (MD) for the group was -3.24 +/- 3.23 dB; 14 eyes of eight patients showed defects (range, -1.62 to -9.46 dB). The square root of the group mean total error score for FM 100-hue was 7.42 +/- 3.84; nine eyes of five patients were classified as abnormal with an unsolved colour axis suggestive of complex drug interactions. For contrast sensitivity, 15 eyes of eight patients yielded abnormal results in one or more spatial frequencies. Defects were more prominent at higher spatial frequencies. Overall, four patients had defects in all three visual-function tests, six patients had mixed defects, and two patients were normal. CONCLUSIONS: Visual-function deficits in epilepsy patients treated with VGB are present in the central 10 degrees of the retina. We recommend a battery of investigations, including SWAP 10-2 and spatial contrast sensitivity testing, to assess central visual function.

Adult↗

Epilepsy patients treated with antiepileptic drug therapy exhibit compromised ocular perfusion characteristics.

PURPOSE: Reduced cerebral blood flow and decreased cerebral glucose metabolism have been identified in patients with epilepsy treated with antiepileptic drug (AED) therapy. The purpose of this study was to determine whether ocular haemodynamics are similarly reduced in patients with epilepsy treated with AEDs. METHODS: Scanning laser Doppler flowmetry was used to measure retinal capillary microvascular flow, volume, and velocity in the temporal neuroretinal rim of 14 patients diagnosed with epilepsy (mean age, 42.0 +/- 0.9 years). These values were compared with those of an age- and gender-matched normal subject group (n = 14; mean age, 41.7 +/- 0.3 years). Student's unpaired two-tailed t tests were used to compare ocular blood-flow parameters between the epilepsy and normal subject groups (p < 0.05; Bonferroni corrected). RESULTS: A significant reduction in retinal blood volume (p = 0.001), flow (p = 0.003), and velocity (p = 0.001) was observed in the epilepsy group (13.52 +/- 3.75 AU, 219.14 +/- 76.61 AU, and 0.77 +/- 0.269 AU, respectively) compared with the normal subject group (19.02 +/- 5.11 AU, 344.03 +/- 93.03 AU, and 1.17 +/- 0.301 AU, respectively). Overall, the percentage mean difference between the epilepsy and normal groups was 36.31% for flow, 28.92% for volume, and 34.19% for velocity. CONCLUSIONS: Patients with epilepsy exhibit reduced neuroretinal capillary blood flow, volume, and velocity compared with normal subjects. A reduction in ocular perfusion may have implications for visual function in people with epilepsy.

Adult↗

The effect of corneal thickness and corneal curvature on pneumatonometer measurements.

PURPOSE: The purpose of this study was to investigate the influence of corneal topography and thickness on intraocular pressure (IOP) and pulse amplitude (PA) as measured using the Ocular Blood Flow Analyzer (OBFA) pneumatonometer (Paradigm Medical Industries, Utah, USA). METHODS: 47 university students volunteered for this cross-sectional study: mean age 20.4 yrs, range 18 to 28 yrs; 23 male, 24 female. Only the measurements from the right eye of each participant were used. Central corneal thickness and mean corneal radius were measured using Scheimpflug biometry and corneal topographic imaging respectively. IOP and PA measurements were made with the OBFA pneumatonometer. Axial length was measured using A-scan ultrasound, due to its known correlation with these corneal parameters. Stepwise multiple regression analysis was used to identify those components that contributed significant variance to the independent variables of IOP and PA. RESULTS: The mean IOP and PA measurements were 13.1 (SD 3.3) mmHg and 3.0 (SD 1.2) mmHg respectively. IOP measurements made with the OBFA pneumatonometer correlated significantly with central corneal thickness (r = +0.374, p = 0.010), such that a 10 microm change in CCT was equivalent to a 0.30 mmHg change in measured IOP. PA measurements correlated significantly with axial length (part correlate = -0.651, p < 0.001) and mean corneal radius (part correlate = +0.459, p < 0.001) but not corneal thickness. CONCLUSIONS: IOP measurements taken with the OBFA pneumatonometer are correlated with corneal thickness, but not axial length or corneal curvature. Conversely, PA measurements are unaffected by corneal thickness, but correlated with axial length and corneal radius. These parameters should be taken into consideration when interpreting IOP and PA measurements made with the OBFA pneumatonometer.

Adolescent↗

Clinical evaluation of the dynamic observing tonometer.

PURPOSE: The Dynamic Observing Tonometer (SmartLens, Ophthalmic Development Company AG, Zürich, Switzerland) is a diagnostic contact lens that allows continuous measurement of intraocular pressure, in addition to providing the investigator with a view of the posterior pole and anterior chamber angle. The purpose of this study was to determine the accuracy of this tonometer and the repeatability of the intraocular pressure measurements. PATIENTS AND METHODS: The intraocular pressure was measured by Goldmann applanation tonometry in one randomly chosen eye of 40 subjects (median age 66 years, range 21-77 years). The intraocular pressure, pulse amplitude and 10-second continuous tonometric recordings were then taken using the Dynamic Observing Tonometer and a pneumatonometer. Accuracy was determined by calculating the mean bias and 95% limits of agreement of measurements made with the Dynamic Observing Tonometer against measurements made with the Goldmann and pneumatonometer. Repeatability was evaluated by calculating the differences between pairs of repeated measurements against the mean value and by calculating reliability coefficients. RESULTS: Intraocular pressure measurements made with the Dynamic Observing Tonometer had a mean bias of +2.1 mm Hg (95% limits of agreement: -4.0 to +8.2 mm Hg) compared with Goldmann tonometry. There was a reasonable correlation between Goldmann and Dynamic Observing Tonometer intraocular pressure readings (r = 0.78, P < 0.01). In measuring pulse amplitude, the Dynamic Observing Tonometer was found to have a mean bias of +0.4 mm Hg (95% limits of agreement: -1.6 to +2.3 mm Hg) compared with the pneumatonometer (r = 0.78, P < 0.01). In assessing the repeatability of intraocular pressure measurements, the first Dynamic Observing Tonometer reading was on average 0.4 mm Hg higher than the second (95% limits of agreement: -3.8 to +4.6 mm Hg) with a coefficient of reliability of 0.91. For pulse amplitude readings, the first reading was on average 0.1 mm Hg lower than the second (95% limits of agreement: -1.4 to +1.2 mm Hg) with a coefficient of reliability of 0.90. CONCLUSION: Intraocular pressure measurements taken with the Dynamic Observing Tonometer had a small positive bias compared with Goldmann tonometry. The pulse amplitude values correlated well with those obtained with a pneumatonometer and the repeatability of intraocular pressure measurements was similar to that found in other commercially available tonometers.

Adult↗

Phase variation of lic1A, lic2A and lic3A in colonization of the nasopharynx, bloodstream and cerebrospinal fluid by Haemophilus influenzae type b.

The role of phase variation of lic1A, lic2A and lic3A in the ability of Haemophilus influenzae type b to colonize the nasopharynx, bloodstream and cerebrospinal fluid (CSF) of infants was investigated. This was achieved by using PCR to determine the number of 5'-CAAT-3' repeats present in each gene, which is indicative of whether each ORF can be expressed. Multiple PCR products of different intensities were amplified from all three genes at each site sampled. This indicated that the nasopharynx, bloodstream and CSF were colonized by a heterogeneous population of organisms, expressing different combinations of lic genes. At each site however, a predominant PCR product was amplified from each gene, indicating that organisms with this genotype were the most abundant. The number of 5'-CAAT-3' repeats in this predominant product varied depending upon whether organisms were isolated from the nasopharynx, bloodstream or CSF. These observations suggest that the expression of different combinations of lic genes may influence the efficiency with which H. influenzae colonizes the nasopharynx, bloodstream and CSF of infant rats.

Animals↗

An in silico evaluation of Tn916 as a tool for generalized mutagenesis in Haemophilus influenzae Rd.

The transposon Tn916 was evaluated as a tool for generalized mutagenesis of the genome of Haemophilus influenzae. This was achieved in silico by searching the genome sequence of H. influenzae Rd for the published Tn916 target site consensus sequence 5' TT/ATTTT(N)6AAAAAA/TA. This search identified 16 putative target sites. In subsequent experiments, integration of Tn916 did not occur at any of these sites. Using the nucleotide sequences of these observed integration sites, a new consensus sequence, 5' TTTTT(N)xAAAAA (4 < or = x < or = 7), was derived. This sequence reflects the curve-twist-curve DNA topology which is a feature common to all Tn916 integration sites. A search of the H. influenzae Rd genome using the new consensus sequence identified 167 potential target sites, representing approximately 1% of the total genome. Only 80 of these sites were located within ORFs. The presence of such a limited number of target sites places severe constraints on the use of Tn916 as a tool for generalized mutagenesis of the genome of H. influenzae.

Base Sequence↗

Autonomic nervous system, circadian rhythms, and primary open-angle glaucoma.

The etiology of primary open-angle glaucoma (POAG) remains the subject of continuing investigation. Despite the many known risk factors and mechanism of damage, the principal treatment objectives in POAG still consist of reduction of intraocular pressure, which although straightforward in many cases, often leaves the clinician with the question of how far to pursue a sufficiently low pressure to prevent further damage. Other risk factors such as hemodynamic insufficiency due to vascular dysregulation and abnormal blood pressure are often overlooked in the day-to-day practice; their harmful effects for glaucoma are, it seems, more potent at night while the patient sleeps and when clinical investigation is most difficult. Although the status of autonomic nervous system is an important determinant of the systemic hemodynamic parameters, this issue is usually ignored by the clinician in the process of glaucoma diagnosis. Consequently, there is a lack of alternative therapies tailored to address associated systemic risk factors for POAG on a case and chronological basis; this approach could be more effective in preventing the progression and visual loss in selected glaucoma cases.

Autonomic Nervous System↗