Andreas Schoetzau

Blood-flow Velocities of the Extraocular Vessels in Patients With High-tension and Normal-tension Primary Open-angle Glaucoma

PURPOSE To evaluate blood-flow parameters in three different groups of patients with primary open-angle glaucoma. METHODS Hemodynamic parameters in the ophthalmic artery, central retinal artery, central retinal vein, and lateral and medial short posterior ciliary arteries were evaluated by color Doppler imaging in 237 patients with primary open-angle glaucoma and 124 age-matched normal control subjects. Group A consisted of 56 patients with primary open-angle glaucoma with treated intraocular pressure higher than 20 mm Hg; group B, of 103 patients with primary open-angle glaucoma with progression of glaucomatous damage despite intraocular pressure of 21 mm Hg or less; and group C, of 78 patients with normal-tension glaucoma. RESULTS All patients showed a significant decrease in end-diastolic velocities (P < .01) and a significant increase in resistivity index (P < .05) in all arteries measured. Peak-systolic velocities were normal in the ophthalmic artery in all three groups. In the central retinal artery and the short posterior ciliary arteries, however, patients in groups B and C had significantly reduced peak-systolic velocity (P < .05) compared with normal control subjects. Peak-systolic velocity in group A did not differ significantly from that of normal control subjects. Maximal and minimal blood-flow velocities in the central retinal vein were significantly lower in groups B and C (P < .001) compared with normal control subjects. In group A, only minimal blood-flow velocity was significantly reduced (P < .05). CONCLUSIONS Hemodynamic parameters in the extraocular vessels are altered in patients with glaucoma. Reduced blood-flow velocities may be secondary as well as contributory to glaucomatous damage.

Blood flow velocity in the extraocular vessels in chronic smokers

AIMS To determine blood flow velocity in the extraocular vessels in healthy, chronic smokers and to compare these blood flow velocities with those of healthy non-smokers. METHODS In 46 healthy chronic smokers and 189 healthy non-smokers, peak systolic velocity (PSV), end diastolic velocity (EDV), and the resistivity index (RI) were measured in the ophthalmic artery (OA), central retinal artery (CRA), lateral short posterior ciliary artery (LPCA), and medial short posterior ciliary artery (MPCA) by means of a colour Doppler device, Siemens Quantum 2000.The maximal (max) and minimal (min) velocities were measured in the central retinal vein (CRV). Only one eye was measured in each subject, and right and left eyes were chosen randomly. Blood flow velocities were compared with one way MANOVA and t tests. The influence of age, sex, systolic and diastolic blood pressure, as well as heart rate on blood flow velocity and RI were evaluated by an analysis of covariance. The potential differences of the influence of the covariables on blood flow variables in smokers and non-smokers were tested by calculating the interactions. RESULTS In the majority of measured vessels blood flow velocity was higher in smokers than in non-smokers. This difference was statistically significant in the OA, CRV, and LPCA. The RI indices were equal or slightly lower in smokers. Furthermore, smokers had significantly lower systolic and diastolic blood pressure. Heart rate was higher in smokers but this difference did not reach statistical significance. CONCLUSIONS Colour Doppler measurements may differ significantly in smokers compared with non-smokers. Therefore, smoking habits should be considered when interpreting colour Doppler imaging results, and comparing different groups of diseased or healthy subjects.

Circumferential viscocanalostomy and suture canal distension (canaloplasty) for whites with open-angle glaucoma.

PurposeTo assess the safety and efficacy of canaloplasty (360-degree viscodilation and tensioning of the Schlemm canal) in Whites with open-angle glaucoma (OAG). MethodsIn a prospective study, 32 consecutive patients with medically uncontrolled OAG underwent primary canaloplasty with a follow-up time of more than 1 year. Laser goniopuncture was performed if postoperative intraocular pressure (IOP) was above 16 mmHg. IOP, number of antiglaucomatous medications, best-corrected visual acuity, and intraoperative and postoperative complications were recorded. Complete success was defined as an IOP ⩽21, 18, and 16 mm Hg without medications, and qualified success with or without medications, respectively. ResultsThe mean IOP dropped from 27.3±5.6 mm Hg preoperatively to 12.8±1.5 mm Hg at 12 months and 13.1±1.2 mm Hg at 18 months (P<0.001). The complete success rate of an IOP ⩽21, 18, and 16 mm Hg was 93.8% [95% confidence interval (CI) 0.86-1.0], 84.4% (95% CI 0.73-0.98), and 74.9% (95% CI 0.61-0.92), respectively, at 12 months. Laser goniopuncture was performed on 6 eyes (18.1%) 3.3±2.1 months postoperatively. The mean IOP was 20.6±4.2 mm Hg before and 14.2±2.2 mm Hg after goniopuncture. The number of medications dropped from 2.7±0.5 before surgery to 0.1±0.3 after surgery (P<0.001). The postoperative best-corrected visual acuity at last visit (0.38±0.45; range: 0 to 1.8) was comparable with that of preoperative values (0.36±SD 0.37; range: 0 to 1.6) (P=0.42). In all but 1 eye, canaloplasty was completed. Minor intraoperative or postoperative complications like Descemet membrane detachment in 2 eyes, elevated IOP in 1 eye, and suprachoroidal passage of the catheter in 4 eyes were encountered. In 1 eye, circumferential cannulation of the Schlemm canal was impossible. ConclusionsCanaloplasty seems to be a promising and effective surgical procedure in Whites with OAG. Postoperative IOP levels are in the low-to-mid-teens. The procedure can be regarded as safe, but has its own profile of complications.

The influence of iris color on the pupillary light reflex

Abstract · Background: This study was carried out to investigate the effect of iris color on the pupillary light reflex (PLR) in normal healthy volunteers. · Methods: Pupil perimetry was performed on 50 healthy volunteers with the Octopus 1-2-3 automated perimeter. Within the 30-deg visual field, 33 test locations were investigated four times. Stimulus parameters were Goldmann size V (1.72°), intensity 1632 cd/m2, stimulus time 200 ms, background illumination 0 cd/m2, and interstimulus interval 3 s. Pupillometric parameters studied were initial pupil size, amplitude (magnitude of pupillary contraction), latency time, contraction time, pre-PLR movement, contraction velocity, and redilation velocity. Pupillometric parameters were investigated by analysis of variance by the independent variables blue and brown irides. · Results: Iris color (blue vs brown) influenced statistically significantly (P<0.05) amplitude (0.504 mm vs 0.594 mm), contraction time (401 ms vs 407 ms), contraction velocity (13.75 mm2/s vs 16.01 mm2/s), and redilation velocity (4.80 mm2/s vs 5.66 mm2/s). Iris color did not influence initial pupil size (4.78 mm vs 4.83 mm), latency time (520 ms vs 521 ms), and pre-PLR movement (0.328 mm2/s vs 0.325 mm2/s). · Conclusions: Pupillary contraction amplitude and velocity depended on iris color, whereas pupil size and latency time were independent of iris color. Therefore, iris color might be considered when evaluating pupillary movements in pupil perimetry.

Relationship between retinal glial cell activation in glaucoma and vascular dysregulation.

PurposeTo investigate the possible relationship between presumed activated retinal astrocytes and Müller cells (ARAM) and primary vascular dysregulation (PVD) in patients with primary open-angle glaucoma (POAG). Patients and MethodsOne hundred eighty-six eyes of 93 patients with POAG were included in the study. Presumed ARAM was defined as patchy, discrete glittering but transparent changes of the retina. The diagnosis of PVD was based on both the patients history and an abnormal circulatory behavior. Frequency tables were used to describe categorical variables, and differences were compared by means of χ2 test. A generalized linear mixed model was applied to determine the influence of vascular dysregulation, mean visual defect, and age on ARAM. ResultsARAM was found to be bilateral in 26.8% of patients (50 eyes), and unilateral in 11.8% (11 eyes). Patients mean age was 68.6 (SD±8.1) years in the group with ARAM and 65.6 (SD±13.6) years in the group without (P=0.56). In the generalized linear mixed model, ARAM was significantly associated with vascular dysregulation [odds ratios (OR): 4.4, confidence intervals (CI): 1.7-11.3, P=0.002] but not with greater age (OR: 1.1 per decade of years, 0.7-1.6, P=0.48) and eye side (OR: 1.1, CI: 0.8-1.6, P=0.52). An increase of mean visual defect of 5.5 dB doubled the risk for ARAM (OR: 2.0; CI: 1.5-2.7, P<0.001). ConclusionsPresumed retinal glial cell activation in POAG is clearly related to vascular dysregulation and to some extent to the stage of glaucomatous damage.

Targeting the ROR1 and ROR2 receptors in epithelial ovarian cancer inhibits cell migration and invasion

AIM In recent years, the Wnt signalling pathway has been implicated in epithelial ovarian cancer and its members have potential as diagnostic, prognostic and therapeutic targets. Here we investigated the role of two Wnt receptor tyrosine kinases (RTKs), ROR1 and ROR2, and their putative ligand, Wnt5a, in ovarian cancer. METHODS Immunohistochemistry for ROR2 was performed in a large patient cohort, including benign controls, borderline tumours and epithelial ovarian cancer. In addition, siRNA was used to silence ROR1, ROR2 and Wnt5a individually, and together, in two ovarian cancer cell lines, and the effects on cell proliferation, adhesion, migration and invasion were measured. RESULTS ROR2 expression is significantly increased in ovarian cancer patients compared to patients with benign disease. In vitro assays showed that silencing either receptor inhibits ovarian cancer cell migration and invasion, and concurrently silencing both receptors has an even stronger inhibitory effect on proliferation, migration and invasion. CONCLUSIONS ROR2 expression is increased in epithelial ovarian cancer, and silencing ROR2 and its sister receptor ROR1 has a strong inhibitory effect on the ability of ovarian cancer cells to proliferate, migrate and invade through an extracellular matrix.

Half a pack of cigarettes a day more than doubles DNA breaks in circulating leukocytes

BackgroundThe mechanisms by which smoking induces damage is not known for all diseases. One mechanism believed to play a role is oxidative stress. Oxidative stress leads to cellular damage including DNA damage, particularly DNA breaks. We conducted this study to test the hypothesis that smokers have increased DNA breaks in their circulating leukocytes.MethodsA comparative quantification of single-stranded DNA breaks was performed by comet assay analysis in the circulating leukocytes of ten healthy smokers (average smoking rate: half a pack a day, range: 9-12 cigarettes a day) and ten age and sex matched healthy non-smokers. DNA breaks lead to smaller pieces of DNA, which migrate out of the nucleus forming a tail during gel-electrophoresis. Damage of an individual cell was quantified by the parameters tail moment and olive moment.ResultsSmoking had a clear effect on both study parameters (tail and olive moment). Smokers had more than double the amount of ss-DNA breaks in their circulating leukocytes than non-smokers [tail moment: 0·75 AU [smokers] compared to 0·2 AU [non-smokers]; olive moment: 0·85 AU [smokers] compared to 0·3 AU [non-smokers]; both p < 0·001].ConclusionSmoking half a pack a day interferes with DNA integrity. One potential explanation for the enhanced DNA breaks in smokers is oxidative stress.

The frequency distribution of blood-flow velocities in the extraocular vessels.

Abstract• Purpose: The study was carried out in order to assess the distribution of normal values of the blood-flow velocity in the extraocular vessels. • Methods: In 240 healthy visitors to a public fair, blood-flow characteristics in the extraocular vessels were measured, and the resistivity index was calculated. Blood-flow velocity was measured with a color Doppler imaging device, using a 7.5-mHz linear-array transducer. Peak-systolic and end-diastolic blood-flow velocities in the arteries were measured, and the resistivity index was calculated. In the central retinal vein the minimal and maximal blood-flow velocities were measured. The statistical analysis of the 14 measured and calculated variables included descriptive statistics, frequency distribution, and quantile plots. • Results: The quantile plots of the cumulative frequency showed that none of these 14 variables are normally distributed. Also, no normal distribution could be achieved by adjustment of the data by age. • Conclusions: The blood-flow velocities in the extraocular vessels measured are not distributed normally. Therefore, nonparametric tests are to be used for statistical analysis if the sample size is small. The estimation of tolerance intervals has to be based on distribution-free assumptions.

Multiple sclerosis and primary vascular dysregulation (Flammer syndrome)

BackgroundMultiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS of still unknown aetiology. Flammer syndrome (FS) encompasses a set of symptoms and signs that are primarily but not solely related to the dysregulation of blood vessels. The purpose of the present study was to determine whether FS symptoms occur more often in MS patients than in controls.MethodsFifty-eight MS patients and 259 controls answered a questionnaire covering 15 symptoms and signs of FS.ResultsSix of the 15 symptoms and signs of FS (dizziness, low body mass index, cold hands and/or feet, tendency toward perfectionism, reduced thirst, feeling cold) were found significantly more often in MS patients than in controls. Seven additional symptoms and signs (tinnitus, headaches, increased pain sensation, long sleep-onset time, migraines, increased response to certain drugs, low blood pressure) also occurred more often in MS patients, but the difference in frequency was not statistically significant. One sign (reversible skin blotches) was found less often in MS patients, but the difference in frequency was not statistically significant. One symptom (increased smell perception) was found significantly less often in MS patients.ConclusionsMS patients suffer significantly more often from FS symptoms and signs than controls. The reason for this association between MS and FS and the potential implications of this association still need to be determined.

Detection of retinal glial cell activation in glaucoma by time domain optical coherence tomography.

BACKGROUND Activated retinal astrocytes and Müller cells (ARAM) have been found in glaucoma patients. This study investigated whether presumed ARAM can be detected by optical coherence tomography (OCT), and assessed their relationship to the retinal nerve fiber layer (RNFL) thickness. PATIENTS AND METHODS Single-center observational study involving 35 age-matched healthy controls and 19 patients with primary open-angle glaucoma (POAG) between 45 - 82 years of age. Presumed ARAM was defined as patchy, discrete glittering but transparent changes of the macula. The retina was documented by red-free photography to assess distribution of ARAM, and compared to the RNFL thickness measured around the fovea by OCT. A linear mixed effects model was used to detect a difference between eyes with ARAM versus eyes without ARAM. RESULTS ARAM was not found in healthy subjects. The mean RNFL around the fovea was not significantly thicker in healthy controls (34.01 SD ± 22.24) than in POAG patients with ARAM (30.86 microns SD ± 15.09; p = 0.36) or without ARAM (33.19 microns SD ± 19.87; p = 0.46). Furthermore, the median RNFL thickness was similar to the control group (29 microns) but slightly thinner in POAG patients (each 27 microns with ARAM and without ARAM). In a subgroup analysis of POAG patients with ARAM, the within subject standard deviation of RNFL was significantly lower in areas with ARAM (SD 10.12) than in areas without ARAM (SD 17.30) (p < 0.001). CONCLUSIONS Although the mean and median RNFL thickness was comparable between the groups, the variability of the RNFL thickness was significantly lower in areas with ARAM than in areas without ARAM suggesting that ARAM may mask RNFL loss in POAG patients.