Retinal neurovascular coupling in patients with glaucoma and ocular hypertension and its association with the level of glaucomatous damage.

PURPOSE: To analyze neurovascular coupling in the retina of untreated primary open-angle glaucoma (POAG) and ocular hypertension (OHT) patients. PATIENTS AND METHODS: Maximal vessel dilation in response to flicker light was analyzed with Retinal Vessel Analyzer (RVA) in temporal superior/inferior arterioles and veins in 51 POAG patients, 46 OHT and 59 control subjects. RVA parameters were compared between groups, between contralateral POAG eyes, and correlated to intraocular pressure, visual field mean defect and retinal nerve fiber layer thickness. RESULTS: POAG eyes demonstrated generally smaller response of all vessels to flicker light than the other two groups (ANOVA p=0.026; mean arterial flicker response in percent of baseline, averaged superior and inferior was 3.48 ± 2.22 % for controls , 2.35 ± 2.06 % for POAG patients , and 2.97 ± 2.35 % for OHT patients; corresponding values for venules were 3.88 ± 1.98 %, 2.89 ± 1.72 %, 3.45 ± 2.77 %). There was no difference in flicker response between the eye with more and less advanced damage in each patient of the POAG group (ANOVA p=0.79). Correlation of flicker response to intraocular pressure (IOP) was borderline at best, correlations to the level of glaucomatous damage were not significant. Correlation of flicker response of superior and inferior vessels of the same eye was significant for the arteries (Pearson r=0.23, p=0.004), as well as venules (r=0.52, p<0.001). CONCLUSION: General vessel response to flicker light was decreased in POAG patients, compared to normal controls and OHT patients. In contrast to significant correlation between the two contralateral eyes of the flicker response itself, only its borderline correlation to IOP was seen. There was no correlation to the level of damage, altogether indicating a systemic dysregulation phenomenon. GRANTS: Swiss National Foundation Grant 3200B0-113685, Velux Stiftung Grant, Freie Akademische Gesellschaft (FAG) Grant, Pfizer Inc. Grant CLINICAL TRIAL REGISTRATION REFERENCE NUMBER: ClinicalTrials.gov NCT00430209.

Dynamics of retinal vessel response to flicker light in glaucoma patients and ocular hypertensives.

PURPOSE: To analyze dynamics of retinal vessel dilation response to flicker light in patients with glaucoma and ocular hypertension. PATIENTS AND METHODS: Response to flicker light was measured in retinal vessels by means of Retinal Vessel Analyzer. After the baseline 50 seconds long diameter recording of inferior and superior temporal artery and vein, three flicker stimulations of 20 seconds duration was applied, with a 80 seconds break in between. Area under the curve of the vessel diameter (AUC) was compared during 3 flicker periods in the open angle glaucoma patients group (POAG, n = 47) and ocular hypertensives (OHT, n = 46) and age-matched healthy controls (n = 56) RESULTS: POAG eyes demonstrated smaller response of all vessels to flicker light in general than the other two groups (p = 0.0008), but the response dynamics was significantly different between the groups (p = 0.038), showing in three flicker periods a delayed increasing response in the POAG and OHT groups, and remaining stable in healthy subjects. CONCLUSION: General vessel response to flicker light was decreased in POAG patients despite the slow improvement in repeated flicker stimulation, indicating an altered response pattern.

Relationship between peripheral blood flow in extremities and choroidal circulation.

BACKGROUND: The aim of this study was to explore the relationship between subjectively estimated and objectively measured finger temperature on the one, and choroidal blood flow on the other side. PATIENTS AND METHODS: We measured submacular choroidal blood flow (CBF) in 73 healthy subjects. Based on the history of cold hands and feet, they were divided in three groups, reporting "never", "sometimes" and "always" having cold extremities. As an objective measure of finger temperature, it was recorded at the fingertips with an infrared thermometer (IRT). Analysis of variance for CBF based on the group selection and with blood and intraocular pressures as covariates was performed, as well as the correlation between CBF and IRT. RESULTS: There were 37 subjects in the group with "never" cold extremities, 20 in the group with "sometimes", and 16 subjects in the group with "always" cold extremities. Average age was 44.2 ± 12.9 years. CBF was 11.5 ± 7.3 AU (arbitrary units), 13.6 ± 6.1 AU and 14.3 ± 4.6 AU in the three groups, respectively. The ANOVA p-value was 0.04. Pearson's R for correlation between CBF and IRT was - 0.51, p < 0.001. CONCLUSION: Subjectively and objectively, colder extremities are associated with higher CBF, possibly due to the redistribution of blood flow.

Olfactory function in primary open-angle glaucoma patients.

PURPOSE: The aim of this study was to assess the olfactory function of primary open-angle glaucoma patients. PATIENTS AND METHODS: We analyzed odour threshold, identification, and discrimination in 30 primary open-angle glaucoma patients and 30 age- and gender-matched healthy control subjects. The "Sniffin' Sticks" test battery was applied sequentially on both sides, scores of two nostrils were averaged and means were compared with Mann-Whitney U-test between the groups. RESULTS: Scores for odour threshold were 5.9 +/- 2.2 and 7.4 +/- 2.1 in glaucoma and control group, respectively (p = 0.01), for odour discrimination 10.5 +/- 2.0 and 10.8 +/- 1.6 (p = 0.65), and for odour identification 11.8 +/- 2.1 and 10.6 +/- 1.6 (p = 0.008). Comparing within glaucoma group between those with (n = 18) and without history (n = 12) of cold hands and feet, the former had significantly better odour threshold scores, 6.6 +/- 1.5, than the latter, 4.8 +/- 2.6 (p = 0.036); no difference in other two olfactory modalities were detected. CONCLUSION: Changes of olfactory function have been described in neurodegenerations such as Alzheimer and Parkinson diseases. Complex alterations of olfactory performance seem to be present in POAG patients as well.

Volumetric blood flow measurement in the ophthalmic artery using colour Doppler.

BACKGROUND: Herewith we present a new method for measurement of the volumetric blood flow in absolute units in the ophthalmic artery. PATIENTS AND METHODS: A Philips EnVisor HD ultrasound unit with a 12 - 3 MHz linear transducer was used to measure flow in the ophthalmic artery in 8 healthy young subjects. The transducer was mounted on a custom-made holder which enabled precise and reproducible positioning in 3 axes as well as in rotation angle. Blood flow velocity and vessel diameter were measured during 10 consecutive heartbeats. The measurements were ECG-gated. Blood vessel diameter and blood flow velocity were calculated in an average heartbeat cycle. Hence blood volume over time within a heartbeat cycle as well as blood flow in mL/min were determined. Simultaneously, cardiovascular parameters have been recorded by Finapres. Short time reproducibility (5 measurements on day 1) and long time reproducibility (5 days once daily) as well as interindividual coefficient of variation were evaluated. RESULTS: Average blood flow in the ophthalmic artery in all measurements was 39.7 mL/min. The short-term intraindividual coefficient of variation was 24.1 +/- 9.2 %, the long-term coefficient 32.0 +/- 13.8 %. Interindividual coefficient of variation was 32.8 %. CONCLUSIONS: Our method allows volumetric blood flow measurements in the ophthalmic artery in absolute units, reproducible to a limited extent.

[Response of retinal vessel diameter to flicker-light in vasospastics compared to healthy controls]. / Flickerlichtprovokation bei Vasospastikern verglichen mit gesunden Kontrollpersonen.

BACKGROUND: Vascular dysregulation is considered to be a risk factor in several ophthalmic diseases. The purpose of this study was to evaluate the reaction of retinal vessels to flicker light in otherwise healthy subjects with a vasospastic propensity. PATIENTS AND METHODS: Thirty healthy Caucasians, aged between 18-35 years were recruited for this study and grouped into vasospastics, based on a history of frequent cold hands, even in summer, with concordant findings in nailfold capillary microscopy, or as controls, if such a history was absent. The reaction of the retinal vascular diameter to flicker light was observed in a distance of two to three discs diameters away from the optic nerve head with the retinal vessel analyser. Three phases of flicker light of twenty seconds followed by baseline light phases of eighty seconds were recorded. The maximal vasodilatory amplitude of each flicker phase was determined and the results averaged. RESULTS: The maximal average dilatory amplitude at the arterial side reached (mean +/- SD) 2.9 +/- 1.7 % and 4.8 +/- 2.6 % of the baseline amplitude respectively in vasospastic subjects and in healthy controls (t = 2.34; p = 0.025). The reaction at the venous side was statistically comparable in both groups. CONCLUSIONS: Otherwise healthy, vasospastic subject disclosed an altered reaction of the retinal vasculature to flicker light in this study.

Relation of body mass index and blood pressure to subjective and objective acral temperature.

BACKGROUND: Vascular dysregulation, indicated by a positive history of cold extremities, has been postulated as a risk factor for a number of ocular diseases. In order to further characterize the phenotype of vasospastic persons, we tested the association between cold extremities, body mass index (BMI) and blood pressure (BP) in a cohort of healthy subjects. PATIENTS AND METHODS: Questionnaire data were collected from one hundred and seventeen healthy subjects. Based on the history of cold hands and feet they were divided in three groups, reporting "never", "sometimes" and "always" having cold extremities. BP was measured sphygmomanometrically and as an objective measure of finger temperature, it was recorded at the fingertips with an infrared thermometer (IRT). Two-way analysis of variance with gender as one, and group selection as the second factor was performed separately for BMI and mean BP. The correlation of finger temperature with BMI and BP was analyzed by the Pearson regression. RESULTS: Gender distribution was male/female = 41/16, 13/21 and 4/22, for the three groups, respectively, and average age 45.8 +/- 13.0 years. For BMI, factor groups was highly significant (p = 0.0012) with both genders behaving comparably (interaction p = 0.18). For BP the corresponding p values were: factor group p = 0.026, interaction p = 0.89. Correlation coefficients between IRT and BMI were 0.34 (p = 0.0002) and between IRT and BP 0.24 (p = 0.009). CONCLUSION: A statistical significant association is present in healthy subjects between body mass index and blood pressure on one, and cold extremities on the other side, defined subjectively as well as measured objectively. This relationship is gender-independent.

Retinal vessels in patients with multiple sclerosis: baseline diameter and response to flicker light stimulation.

BACKGROUND: Transparency of ocular media enables the precise quantitative analysis of vessels of retina, a neuronal tissue which can be affected by multiple sclerosis (MS). PATIENTS AND METHODS: Eyes with no history of optic neuritis (non-ON eyes) of 21 patients with MS were examined with Retinal Vessel Analyzer. Segments of vessels of 500 microm length were measured proximal and distal from the optic disc and compared to those of 21 age- and gender-matched controls. Baseline diameters and peak response to flicker light stimulation of retinal vessels were analyzed. RESULTS: MS eyes had thinner arterioles (p = 0.02) and thicker venules (p = 0.008) than controls: arterioles 111 +/- 14 microm (proximal), 99 +/- 11 microm (distal) in MS eyes and 121 +/- 15 and 107 +/- 9 in controls, respectively. Values for venules were 157 +/- 18 and 136 +/- 20 (MS); 147 +/- 15 and 119 +/- 20 (controls). Peak response was higher in MS eyes than in controls for arterioles (p = 0.007), but comparable for venules (p = 0.35). CONCLUSION: Narrower arterioles and wider venules might be a consequence of subclinical swelling of optic nerve axons in eyes with negative history of ON in MS patients.

Rigidity of retinal vessels in patients with multiple sclerosis.

PURPOSE: The aim of this study was to analyze pulse wave propagation in the ocular circulation by assessing the phase delay between retinal arterioles and venules and calculating the pulse delay between the retinal and choroidal circulations in MS patients and in control subjects. SUBJECTS AND METHODS: Twenty patients with multiple sclerosis (38.3 +/- 6.2 years) and twenty healthy subjects (37.4 +/- 15.2 years) were examined with the Retinal Vessel Analyzer. In addition, an average peripapillary RNFL (retinal nerve fiber layer) thickness was measured by means of ocular coherence tomography in MS patients. The phase delay between the arteriole and venule pulsations was assessed at three sites: in the close retinal vicinity of the disc, 1 - 2 disc diameters and 3 - 4 disc diameters away from the disc. Assuming that venules are counterphased to the choroidal circulation, a choroid-to-retina pulse delay was calculated. RESULTS: The choroid-to-retina pulse delay was 0.26 +/- 0.11, 0.27 +/- 0.13 and 0.34 +/- 0.15 sec in eyes with history of optic neuritis (ON-eyes); in eyes of MS patients without such a history (non-ON eyes) the corresponding values were 0.27 +/- 0.14, 0.29 +/- 0.11 and 0.30 +/- 0.15 sec, and in control eyes 0.32 +/- 0.19, 0.38 +/- 0.16 and 0.45 +/- 0.20 sec, respectively, at three sites centrifugal from the disc. The choroid-to-retina pulse delay was significantly longer in healthy control eyes than both in ON eyes (p = 0.012) and non-ON eyes of MS patients (p = 0.004). The interocular difference of the choroid-to-retina pulse delay and OCT RNFL thickness showed a significant correlation in MS patients (Pearson r = 0.54, p = 0.015; Spearman R = 0.66, p = 0.0016). CONCLUSION: Patients with multiple sclerosis seem to demonstrate an increased rigidity of the retinal vessels. The interocular difference in retinal vessel rigidity was significantly correlated with the interocular difference in RNFL thickness in MS patients.

[Central corneal thickness and retrobulbar blood flow in glaucoma patients]. / Hornhautdicke und retrobulbärer Blutfluss bei Glaukompatienten.

BACKGROUND: A correlation between a thin cornea and the presence of vascular risk factors has recently been reported in normal-tension glaucoma patients. The present study intended to investigate the correlation between central corneal thickness and basal retrobulbar blood flow in glaucoma patients. PATIENTS AND METHODS: Corneal pachymetry and colour Doppler imaging (CDI) of the retrobulbar arteries (ophthalmic, central retinal and cilliary) were performed in 63 glaucoma patients. Linear mixed effect models were used to evaluate the association of central corneal thickness and retrobulbar blood flow. RESULTS: There was no significant correlation between central corneal thickness and blood flow in any of the assessed arteries (p = 0.13-0.88). CONCLUSIONS: A statistical relationship between central corneal thickness and retrobulbar blood flow could not be found in the examined sample of glaucoma patients.

Detection of visual field progression in glaucoma.

BACKGROUND: The aim of this study was to compare an event analysis and a trend analysis for the detection of progression in glaucomatous visual field loss. PATIENTS AND METHODS: Excluding initial fields (Octopus, Haag-Streit AG, Köniz, Switzerland), baseline was defined as the average result of the second and third examinations. Eyes with at least 6 additional fields entered the study. The event analysis used the method of the Collaborative Normal Tension Glaucoma Study, and the trend analysis was based on a point-wise linear regression analysis. RESULTS: Of 251 glaucoma patients, 235 left eyes and 225 right eyes qualified for the study. Using the event analysis, 44 series suggested a progressive damage, while the point-wise regression approach disclosed only 14 progressing series. In 9 eyes, the two approaches were concordant. Among the latter, 1 - 5 additional fields were necessary in 7 series to disclose progression using the trend analysis. In one series, the event analysis showed progression 7 examinations later. CONCLUSIONS: The point-wise linear regression analysis classified fewer cases as progressing than the event analysis and determined progression later.

Pattern of macular thickness changes measured by ocular coherence tomography in patients with multiple sclerosis.

BACKGROUND: An analysis of the pattern of retinal thickness changes in macula in patients with multiple sclerosis (MS) was performed. PATIENTS AND METHODS: In fifteen patients with MS retinal thickness measurements in the central (fovea plus inner macular ring) and peripheral (outer ring) macula obtained by ocular coherence tomography (OCT-3 device) were compared to those of 15 age-matched healthy controls. RESULTS: Eyes of MS patients had on the average a thinner macula (241.8 +/- 20.6 micrometers) than control eyes (252.0 +/- 16.4, p value 0.038). Significant segmental differences occurred in the central macula (p = 0.013). Eight eyes with a positive history of optic neuritis (ON) had on average a thinner macula (226.8 +/- 14.0) than eyes of MS patients without a history of ON (non-ON eyes: 247.3 +/- 20.1, p value 0.01). The only measure significantly different between non-ON and control eyes was the ratio between the central and peripheral macular thickness (p = 0.017). Average macular thickness in non-ON eyes, unlike control eyes (r = - 0.63, p = 0.0002), did not correlate with age (r = 0.01, p = 0.97), however, it did show a borderline correlation with disease duration (r = - 0.41, p = 0.056). CONCLUSIONS: Preferential thinning in the central relative to the peripheral macular region is present in eyes of patients with MS. The macular thickness pattern is likely due to the histological distribution of nerve fibre layer and retinal ganglion cell in the macular area and seems to be particularly informative of neurodegeneration in the eyes of MS patients without a history of optic neuritis.