Variability of contour line alignment on sequential images with the Heidelberg Retina Tomograph

•Background: The influence of the contour line alignment software algorithm on the variability of the Heidelberg Retina Tomograph (HRT) parameters remains unclear. •Methods: Nine discrete topographic images were acquired with the HRT from the right eye in six healthy, emmetropic subjects. The variability of topometric data obtained from the same topographic image, analyzed within different samples of images, was evaluated. A total of four mean topographic images was computed for each subject from: all nine discrete images (A), the first six of those images (B), the last six of those nine images (C), and the first three combined with the last three images (D). A contour line was computed on the mean topographic image generated from the nine discrete topographic images (A). This contour line was then applied to the three other mean topographic images (B, C, and D), using the contour line alignment in the HRT software. Subsequently, the contour line on the mean topographic images was applied to each of the discrete members of the particular images subsets used to compute the mean topographic image, and the topometric data for these discrete topographic images was computed successively for each subset. Prior to processing each subset, the contour line on the discrete topographic images was deleted. This strategy provided a total of three analyses on each discrete topographic image: as a member of the nine images (mean topographic image A), and as a member of two subsets of images (mean topographic image B, C, and/or D). The coefficient of variation (100×SD/mean) of the topographic parameters within those three analyses was calculated for each discrete topographic image in each subject ("intraimage” coefficient of variation). In addition, a coefficient of variation between the nine discrete topographic images ("interimage” coefficient of variation) was calculated. •Results: The "intraimage” and "interimage” variability for the various topographic parameters ranged between 0.03% and 3.10% and between 0.03% and 24.07% respectively. The "intraimage” coefficients of variation and "interimage” coefficients of variation correlated significant (r 2=0.77;P<0.0001). •Conclusion: A high "intraimage” variability, i.e. a high variability in contour line alignment between sequential images, might be an important source of test re-test variability between sequential image

Retinal vascular diameter in young subjects with a vasospastic propensity

Purpose: Retinal vascular diameters have recently been shown not to be related to an increased risk of open-angle glaucoma. Because vasospastic propensity has been suggested to represent a risk factor for various ocular diseases, especially glaucoma, the steady-state retinal vascular diameter in subjects with a propensity for systemic vascular dysregulation was compared with a group of age-matched gender-matched controls. Methods: Thirty healthy non-smoking individuals [female/male 26/4; mean±SD age 22.8±3.4 (range 18-31) years] were enrolled into the study. Subjects were classified as having vasospasm (15 subjects) if they related a clear history of frequently cold hands and as healthy subjects (15 subjects) if they denied such a history. Vasospastic propensity or the absence of it had to be confirmed by nail-fold capillaroscopy. Vascular diameter of retinal vessels was measured repeatedly on two days with the retinal vessel analyser and corrected for perfusion pressure, age, and refraction. Results: Neither retinal arteriole diameter (P=0.30) or retinal venule diameter (P=0.49), nor retinal arteriole-to-venule ratio (P=0.96), differed between the two experimental groups. Conclusions: Although vasospastic propensity has been suggested to represent a risk factor in various ocular diseases, the steady-state retinal vessel diameters are not altered in healthy vasospastic subjects. It is probable that the steady-state retinal vessel diameters are no adequate risk indicators for the haemodynamic risk in diseases such as glaucom

The 2-global flash mfERG in glaucoma: attempting to increase sensitivity by reducing the focal flash luminance and changing filter settings

Purpose: To test a new 2-flash multifocal electroretinogram (mfERG) paradigm in glaucoma using a reduced light intensity of the m-frame flash as opposed to the global flash, as it has been suggested that this may increase the responses induced by the global flash, which has been the part of the mfERG response where most changes have been noted in glaucoma. Methods: A mfERG was recorded from one eye of 22 primary open angle glaucoma (POAG) patients [16 normal tension glaucoma (NTG), 6 high tension glaucoma (HTG)] and 20 control subjects. A binary m-sequence (2^13-1, L max 100cd/m2, L min <1cd/m2), followed by two global flashes (L max 200cd/m2) at an interval of 26ms (VERIS 6.0™, FMSIII), was used. The stimulus array consisted of 103 hexagons. Retinal signals were amplified (gain=50K) and bandpass filtered at 1-300Hz. For each focal response, the root mean square was calculated. We analyzed 5 larger response averages (central 15° and 4 adjoining quadrants) as well as 8 smaller response averages (central 10° and 7 surrounding response averages of approximately 7° radius each). Three epochs were analyzed: the direct component at 15-45ms (DC) and the following two components induced by the effects of the preceding focal flash on the response to the global flashes at 45-75ms (IC-1) and at 75-105ms (IC-2). Statistical analysis was performed using linear mixed effects models adjusted for age. Results: Responses differed significantly between POAG patients and controls in all central response averages. This difference was larger for the central 10° than for the response average of the central 15°. While these observations held true for all response epochs analyzed, the DC differed least and the IC-1 most when POAG was compared to control. For POAG, the most sensitive differential measure was IC-1 of the central 10° with an area under the ROC curve of 0.78. With a cutoff value of 12.52nV/deg2, 80% of the POAG patients (100% HTG, 69% NTG) were correctly classified as abnormal, while 77% of the control subjects were correctly classified as normal. When the results of the mfERG were compared to the visual fields, there was a tendency for the mfERG to decrease as the mean defect increased. However, this correlation was only significant in the superior nasal quadrant when the IC-1 of the mfERG was compared to the corresponding area of the visual field. Conclusion: When compared to findings from previous studies, reducing the luminance of the m-frame flash in the 2-global flash paradigm did not increase the sensitivity and specificity of the mfERG to detect glaucoma furthe

Vasospastic individuals demonstrate significant similarity to glaucoma patients as revealed by gene expression profiling in circulating leukocytes

PURPOSE: There is growing evidence that vasospatic individuals could be predisposed to develop glaucoma. Vasospastic deregulation is ensuing in activation of circulating leukocytes. In previous studies using "gene-hunting" strategies, we demonstrated stable alterations in gene expression profiles of circulating leukocytes isolated from glaucoma patients with vascular deregulation when compared to healthy individuals with no history of glaucomatous damage. The goal of this study was to look for possible similarities in gene expression profiles of circulating leukocytes in vasospastic individuals and glaucoma patients. METHODS: Normal-tension (NTG) and high-tension (HTG) glaucoma patients as well as individuals with vascular deregulation (VD) and healthy controls were recruited for the gene expression analysis. The methodology of comparative Expression Array analysis followed by highly sensitive quantitative real-time PCR has been used. RESULTS: Compared to the control group the expression of 146, 68, and 60 genes was found to be altered in NTG, HTG, and VD groups respectively. Thirty-four genes demonstrated similar expressional alterations in NTG, HTG, and VD groups versus controls, and only 21 genes demonstrated similar expressional alterations in NTG and HTG groups, having no overlap with the VD group. CONCLUSIONS: This result indicates a potential predisposition of vasospastic individuals to glaucomatous optic nerve atrophy. The targeted expression profiles might be further considered for early/predictive glaucoma diagnosis

Comet assay analysis of single–stranded DNA breaks in circulating leukocytes of glaucoma patients

PURPOSE: To investigate the amount of single-stranded DNA breaks in circulating leukocytes of primary open-angle glaucoma (POAG) patients. METHODS: A comparative quantification of DNA breaks was performed in circulating leukocytes of POAG patients and healthy controls. The following groups of subjects were compared: (1) POAG patients having primary vascular dysregulation (PVD), (2) POAG patients without PVD, (3) healthy controls with PVD, and (4) healthy controls without PVD. The damage to DNA resulting in single-stranded breaks was assessed by means of the alkaline comet assay in which the damaged DNA migrates out of the nucleus forming a tail, which can be quantified using image analysis. Damage was quantified as the comet tail moment, which represents the extent of DNA damage in individual cells. RESULTS: Leukocytes of POAG patients exerted a significantly higher amount of comet tails, which are indicative of DNA damage, in comparison to control leukocytes (p>0.001). DNA breaks occurred particularly in the subgroup of POAG patients with PVD in comparison to glaucoma patients without PVD (p=0.002). In the control group, there was no significant difference between controls with PVD and controls without PVD (p=0.86). CONCLUSIONS: POAG patients with PVD have a significantly higher rate of DNA breaks than both POAG patients without PVD and healthy controls with and without PVD

Relationship between gender role, anger expression, thermal discomfort and sleep onset latency in women

ABSTRACT: BACKGROUND: Women with thermal discomfort from cold extremities (hands and feet; TDCE) often suffer from prolonged sleep onset latency (SOL). Suppressed anger could contribute to the genesis of both TDCE and prolonged SOL. The aim of the study was to test the hypothesis whether stereotypic feminine gender socialization (SFGS) is related to anger suppression (experienced anger inwards, Anger-In), which in turn could affect TDCE and SOL. METHODS: 148 women, a sub-sample of a larger survey carried out in the Canton Basel-Stadt (Switzerland), sent back detailed postal questionnaires about SOL, TDCE, anger expression (STAXI, state -trait -anger -expression -inventory) and SFGS using a gender power inventory, estimating the degree of gender specific power expression explicitly within women by stereotypic feminine or male attribution. Statistics was performed by path analysis. RESULTS: A significant direct path was found from stereotypic feminine attribution to Anger-In and prolonged SOL. Additionally, a further indirect path from Anger-In via TDCE to SOL was found. In contrast, stereotypic male attribution was not related to Anger-In but was significantly associated with outwardly expressed anger. LIMITATIONS: Self-reported data, retrospective cross-sectional survey, prospective studies are required including physiological measurements. CONCLUSION: Stereotypic feminine gender socialization may play an important determinant for anger suppression, which subsequently can lead to thermal discomfort from cold extremities and prolonged sleep onset latency

Circulatory response to blood gas pertubations

PURPOSE. To investigate the response of the optic nerve head and the choroidal circulation to blood gas perturbations in otherwise healthy subjects with a history of cold hands. METHODS. Thirty-five healthy subjects were selected and grouped according to the related history of cold hands. All 12 selected male subjects, aged 21 to 38 years (mean Ϯ SD ϭ 28 Ϯ 5.2 years) had a negative history of cold hands. Female subjects were almost equally divided between the groups with a negative (11 subjects, aged 18 -36 years; mean, 25.7 Ϯ 5.5) or positive (12 subjects, aged 19 -45 years; mean, 25 Ϯ 6.8) history of cold hands. Blood gas perturbations were created by having subjects breath a gas mixture consisting of 21% O 2 , 74% N 2 , and 5% CO 2 . The partial pressures pCO 2 and pO 2 were continuously monitored transcutaneously. Choroidal and optic nerve head blood flow response was evaluated by means of laser Doppler flowmetry. RESULTS. Systolic and diastolic blood pressure (SBP/DBP at baseline, three-group average: 111.2/71.9 mm Hg), heart rate (HR; 70.3 bpm), and intraocular pressure (IOP; 14.7 mm Hg) increased during the blood gas perturbation phase (123.1/77.7 mm Hg, 78.5 bpm, and 15.6 mm Hg, respectively) and returned to baseline in the recovery phase (109.9/73.4 mm Hg, 69.5 bpm, and 13.5 mm Hg, respectively). There was no difference between groups (one-way ANOVA of the percentage change from baseline for SBP, P ϭ 0.75; DBP, P ϭ 0.36; HR, P ϭ 0.95; and IOP, P ϭ 0.72). pCO 2 increased from 5.52 to 6.59 kPa and returned to 5.50 kPa. pO 2 increased from 10.64 to 13.12 kPa and returned to 10.73 kPa. Again, there was no difference between groups (one-way ANOVA for the percentage change: pCO 2 , P ϭ 0.17; pO 2 , P ϭ 0.78). In the women with vasospasm, optic nerve head blood flow increased 17.1% and the choroidal blood flow decreased Ϫ3.6%, whereas in the women and men without vasospasm the optic nerve head blood flow decreased Ϫ5.8% and -4.8%, and the choroidal blood flow increased 13.3% and 18.3%, respectively (two-way ANOVA interaction; P ϭ 0.001). CONCLUSIONS. The pCO 2 increase was accompanied by a pO 2 increase. Blood pressure and HR increased comparably in all groups, indicating sympathetic arousal. The women with vasospasm demonstrated an inverse response pattern of choroidal and optic nerve head circulation to blood gas perturbation compared with the women without vasospasm and compared with the men. (Invest Ophthalmol Vis Sci. 2005;46:3288 -3294

Intensity-based Choroidal Registration Using Regularized Block Matching

Detecting and monitoring changes in the human choroid play a crucial role in treating ocular diseases such as myopia. However, reliable segmentation of optical coherence tomography (OCT) images at the choroid-sclera interface (CSI) is notoriously difficult due to poor contrast, signal loss and OCT artefacts. In this paper we present blockwise registration of successive scans to improve stability also during complete loss of the CSI-signal. First, we formulated the problem as minimization of a regularized energy functional. Then, we tested our automated method for piecewise Intensity-based Choroidal rigid Registration using regularized block matching (ICR) on 20 OCT 3D-volume scan-rescan data set pairs. Finally, we used these data set pairs to determine the precision of our method, while the accuracy was determined by comparing our results with those using manually annotated scans

Thermal discomfort with cold extremities in relation to age, gender, and body mass index in a random sample of a Swiss urban population

<p>Abstract</p> <p>Background</p> <p>The aim of this epidemiological study was to investigate the relationship of thermal discomfort with cold extremities (TDCE) to age, gender, and body mass index (BMI) in a Swiss urban population.</p> <p>Methods</p> <p>In a random population sample of Basel city, 2,800 subjects aged 20-40 years were asked to complete a questionnaire evaluating the extent of cold extremities. Values of cold extremities were based on questionnaire-derived scores. The correlation of age, gender, and BMI to TDCE was analyzed using multiple regression analysis.</p> <p>Results</p> <p>A total of 1,001 women (72.3% response rate) and 809 men (60% response rate) returned a completed questionnaire. Statistical analyses revealed the following findings: Younger subjects suffered more intensely from cold extremities than the elderly, and women suffered more than men (particularly younger women). Slimmer subjects suffered significantly more often from cold extremities than subjects with higher BMIs.</p> <p>Conclusions</p> <p>Thermal discomfort with cold extremities (a relevant symptom of primary vascular dysregulation) occurs at highest intensity in younger, slimmer women and at lowest intensity in elderly, stouter men.</p

Regulation of oxygen saturation in retinal blood vessels in response to dynamic exercise

Purpose: To evaluate the impact of dynamic exercise on retinal vessel oxygen saturation in healthy individuals. Methods: Twenty-six healthy participants underwent moderate dynamic exercise (modified Master’s two step exercise). All subjects intraocular pressures (IOP), systolic and diastolic blood pressure (SBP and DBP), retinal vessel calibres and retinal arterial and venous oxygen saturation was measured at baseline, immediately following exercise and 15 minutes post exercise. Results: Moderate dynamic exercise increased systolic and diastolic blood pressures immediately post exercise (SBP: 116 (+/-13) mmHg to 150 (+/-21) mmHg; p<0.001 and DBP: 69 (+/-10) mmHg to 74 (+/-10); p<0.001) while IOP decreased by an average of 2 mmHg (baseline: 13 (+/-3) mmHg)) immediately post exercise (11 (+/-2) mmHg). Oxygen saturation in retinal arteries remained unchanged (baseline= 93 +/-8%; immediately post exercise=94 +/-9% and 15 minutes post exercise=96 +/-8%; p=0.069) but increased in retinal veins immediately post exercise and did not return to baseline values within 15 minutes post exercise (baseline=54 +/-12%; immediately post exercise=56 +/-15%; 15 minutes post exercise=57 +/-12%; p=0.036).  Conclusion: There is a mild increase in retinal venous oxygen saturation and a trend towards an increase in arterial saturation in otherwise healthy individuals following dynamic exercise