A 10-year follow-up of the European multicenter trial of interferon ß-1b in secondary-progressive multiple sclerosis.

OBJECTIVES: To explore long-term effects of treatment and prognostic relevance of variables assessed at baseline and during the European secondary progressive multiple sclerosis (SPMS) trial of interferon beta 1b (IFNB-1b). METHODS: We assessed 362 patients (60% female; median age 41 years; Expanded Disability Status Scale (EDSS): 5.5; 51% randomized to IFNB-1b) for their EDSS and treatment history after 10 years. Non-parametric analysis of covariance (ANCOVA) and multivariate linear regression models were applied. RESULTS: Median EDSS was 6.0 at the end of the randomized controlled trial (RCT), in the IFNB-1b and placebo groups, and 7.0 in long-term follow-up patients (those receiving IFNB-1b in the RCT were 6.5 and those receiving placebo in the RCT were 7.0; p = 0.086). 24 patients (6.6%) were deceased. The EDSS at baseline and the EDSS change during the RCT were the most important predictors of the EDSS 10 years later (partial R(2): 0.47). The ability to predict changes in EDSS 10 years after the RCT was limited (R(2): 0.12). Magnetic resonance imaging (MRI) measures remained in the predictive models, but explained < 5% of the variability. CONCLUSIONS: The results from this analysis did not provide convincing evidence to support a favorable long-term outcome in those patients allocated IFNB-1b during the RCT, in our SPMS cohort. The progressive stage of the disease remains largely unpredictable by clinical and conventional MRI measures, so better prognostic markers are needed.

Analysis of risk factors for long-term glaucomatous damage development.

PURPOSE: The aim of this study was to analyze predictors of long-term glaucoma progression. PATIENTS AND METHODS: We followed 17 primary open angle glaucoma patients (POAG) and 25 ocular hypertensives (OHT) over three years, with regular follow-up examinations of both eyes every 6 months. Glaucoma damage was quantified by optical coherence tomography (retinal nerve fiber layer - OCT RNFL) and by perimetry. Corneal and hand temperature (infrared thermometer), corneal hysteresis, pachymetry and ocular pulse amplitude (OPA) readings were taken at baseline, and applanatory intraocular pressure and retinal vessel analysis recordings were made at baseline and follow-up visits. Forward-stepwise multiple regression analysis was performed. RESULTS: With OCT-RNFL progression as the dependent variable, the model selected initial diagnosis (OHT less probable of progressing), baseline RNFL thickness, retinal arterial and venous diameter and arterial flicker response as significant damage predictors. For visual field damage progression, these were: corneal temperature, OPA, initial diagnosis and venous flicker response (all p<0.05). CONCLUSION: Initial damage and vascular factors are strong predictors of future glaucoma progression.

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.

[Analysis of retinal vein motion in glaucoma patients]. / Analyse der Venenbewegungen in der Netzhaut von Glaukompatienten.

BACKGROUND: Analysis of retinal vein amplitude in eyes of glaucoma patients. PATIENTS AND METHODS: Motion of retinal veins was captured by Retinal Vessel Analyzer in duration of 30 seconds. Inferotemporal vein segments of 500 micrometers length in the immediate vicinity of, as well as away from the optic disc were chosen. Time behavior of the average segment diameter was analyzed by the self made software: dominating frequency (heart rate) was determined by Fourier analysis, and based on this an average pulse form was produced. Difference between the highest and lowest diameter point was the subject of analysis in 25 eyes of 25 glaucoma patients and 25 age-sex-matched healthy controls. RESULTS: Pulse amplitude of retinal veins in healthy eyes was higher than in glaucoma patients: in the optic disc vicinity the pulse amplitude relative to baseline was 2.6 ± 2.1% in control eyes and 1.4 ± 0.8% in glaucoma eyes (t-test, p = 0.009). Away from the disc, it was 1.7 ± 1.0% and 1.1 ± 0.5% respectively (p = 0.01). CONCLUSIONS: Retinal veins in glaucoma eyes demonstrate lower pulse amplitudes than healthy eyes, indicating disturbance in venous outflow and increased intraluminal venous pressure.

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.

Choroidal laser Doppler flowmetry in healthy subjects.

OBJECTIVE: To evaluate normal choroidal blood flow and its relationship with various factors such as age, systemic blood pressure, and intraocular pressure (IOP). METHODS: A total of 70 healthy subjects were recruited. Choroidal blood flow was assessed using a method based on laser Doppler flowmetry (LDF) technique. The LDF parameters of velocity, volume, and flux were obtained. The influence of age, mean systemic blood pressure, IOP, smoking, and sex on choroidal hemodynamic parameters was assessed in a multiple linear regression model. The correlations between interocular difference in IOP and interocular differences in the LDF parameters were assessed by means of the Pearson linear correlation factor. RESULTS: Velocity decreased significantly (P = .03) with advancing age of the subjects and volume increased significantly (P = .02) with increasing IOP. Mean blood pressure, smoking, and sex had no influence on the choroidal LDF parameters. Interocular difference in IOP correlated significantly with interocular difference in volume (R = 0.34, P<.005). CONCLUSION: Choroidal blood flow velocity decreased with increasing age of the subjects, while the volume of moving erythrocytes decreased with lower IOP.

Is vascular regulation in the central retinal artery altered in persons with vasospasm?

OBJECTIVE: To assess the relation between ocular perfusion pressure and blood flow velocity in the central retinal artery in patients with acral vasospasm. SUBJECTS AND METHODS: Eighteen otherwise healthy subjects with acral vascular dysregulation, as demonstrated by nail-fold capillaroscopy, and 18 age- and sex-matched healthy volunteers without vasospasm were recruited. After subjects had rested for 20 minutes in a supine position, intraocular pressure and blood flow velocity in the central retinal artery were determined by applanation tonometry and color Doppler imaging, respectively. The peak systolic velocity, end-diastolic velocity, and resistivity index were assessed. Correlations between the mean ocular perfusion pressure (2/3 x [2/3 x diastolic blood pressure + 1/3 x systolic blood pressure] - intraocular pressure) and blood flow velocities in the central retinal artery were determined by the Pearson linear correlation factor. The Student t test was used to evaluate differences between controls and subjects with vasospasm. RESULTS: The mean +/- SD ocular perfusion pressure was 42.0 +/- 7.4 mm Hg in the group with vasospasm and 47.1 +/- 6.5 mm Hg in the control group (P= .04). In the subjects with vasospasm, the peak systolic and end-diastolic velocities and the resistivity index of the central retinal artery correlated significantly with the mean ocular perfusion pressure (R = 0.49, P = .04 P = .01; and R = -0.67, P = .002, respectively). Such correlations were not found in the control group. CONCLUSIONS: An altered blood flow regulation is suggested in the ocular circulation of patients with acral vasospasm.

Physiology of perfusion as it relates to the optic nerve head.

Blood flow in the optic nerve has been demonstrated to be autoregulated, and, thus, within certain limits, to be independent of the local perfusion pressure. As in the brain, a close coupling of neuronal activity and optic nerve head blood flow has been demonstrated. A number of regulatory systems and factors participate in the regulation of vascular tone in various organs, including the optic nerve. Metabolic and myogenic mechanisms keep local perfusion constant or adapted to the local metabolic needs. Such mechanisms seem to be involved in the regulation of optic nerve blood flow as well. In contrast, neuronal blood flow regulation is of minor importance in the optic nerve. Many of the regulatory modalities induce a response of vascular smooth muscle cells through stimulation of factors produced by the endothelial cell layer. Indeed, endothelial factors are of utmost importance in the regulation of optic nerve blood flow. The facts that there is a basal formation of nitric oxide, which leads to an active dilation of the ocular vasculature, and that endothelin-1 decreases blood flow to the anterior optic nerve in a dose-dependent manner suggest that alterations in these regulatory mechanisms might be relevant for optic nerve blood flow alterations as they relate to glaucomatous optic neuropathy. It is hoped that a detailed knowledge of blood flow regulation in the optic nerve might initiate new treatment modalities in optic neuropathies that are hemodynamic and vascular in nature.

Retrobulbar blood flow in glaucoma patients with nocturnal over-dipping in systemic blood pressure.

PURPOSE: To evaluate the relationship between the circadian blood pressure rhythm and the retrobulbar blood flow in glaucoma patients. DESIGN: Cross-sectional study. METHODS: Circadian blood pressure measurements and color Doppler imaging (CDI) in the ophthalmic artery as well as the central retinal artery of one randomly selected eye were obtained in 193 primary open-angle glaucoma patients. CDI parameters were compared by means of analysis of covariance between patients with a nocturnal decrease in mean systemic blood pressure (MBP) below 20% of the average daytime MBP (over-dippers), patients with a decrease between 10% to 20% (dippers), and patients with a decrease of less than 10% (nondippers), using age, intraocular pressure (IOP), and MBP during color Doppler measurement as covariates. RESULTS: An analysis of covariance disclosed, after correcting for age, IOP, and MBP during color Doppler imaging, a significantly lower EDV (P =.0096) and a significantly higher RI (P =.033) in the central artery of over-dipping glaucoma patients compared with nondippers or dippers. This effect seemed independent of the use of vasoactive drugs . CONCLUSIONS: Glaucoma patients with a marked drop in nocturnal systemic blood pressure seem to have altered retrobulbar blood flow parameters, suggesting that an abnormal systemic blood pressure profile may be the manifestation of some kind of systemic vascular dysregulation relevant for the ocular circulation.

Interocular difference in progression of glaucoma correlates with interocular differences in retrobulbar circulation.

PURPOSE: To evaluate the correlation between interocular difference in progression of glaucomatous damage and interocular differences in retrobulbar blood flow. METHODS: On the basis of a retrospective analysis of visual fields, progressive damage was identified in 20 patients with primary open-angle glaucoma. As a parameter of interocular difference in progression of visual field damage, the angle (gamma) between the regression lines of the visual field index mean defect over time per eye was calculated for each subject. The relationship between the angle gamma and interocular differences in intraocular pressure and retrobulbar color Doppler imaging parameters was analyzed by a multiple linear regression analysis in a stepwise forward approach. RESULTS: With larger interocular differences in progression of glaucomatous damage, lower mean blood flow velocities in the ophthalmic artery (partial r = -.69; P <. 0016), higher resistivity indices in the central retinal artery (partial r =.48; P <.0456), and higher peak systolic velocities in the ophthalmic artery (partial r =.52; P <.0285) were noted in the eyes with more marked progression of damage (multiple r =.71; P <. 0099). Interocular differences in progression of visual field damage were not related to intraocular pressure or extent of visual field damage. CONCLUSION: Independent of the extent of the interocular difference in glaucomatous damage and intraocular pressure, interocular difference in progression of glaucomatous visual field damage correlates with interocular difference in retrobulbar hemodynamic parameters.

Relationship between ocular perfusion pressure and retrobulbar blood flow in patients with glaucoma with progressive damage.

PURPOSE: To evaluate the relationship between ocular perfusion pressure and color Doppler measurements in patients with glaucoma. MATERIALS AND METHODS: Twenty patients with primary open-angle glaucoma with visual field deterioration in spite of an intraocular pressure lowered below 21 mm Hg, 20 age-matched patients with glaucoma with stable visual fields, and 20 age-matched healthy controls were recruited. After a 20-minute rest in a supine position, intraocular pressure and color Doppler measurements parameters of the ophthalmic artery and the central retinal artery were obtained. Correlations between mean ocular perfusion pressure and color Doppler measurements parameters were determined. RESULTS: Patients with glaucoma showed a higher intraocular pressure (P <.0008) and a lower mean ocular perfusion pressure (P <.0045) compared with healthy subjects. Patients with deteriorating glaucoma showed a lower mean blood pressure (P =.033) and a lower end diastolic velocity in the central retinal artery (P =.0093) compared with normals. Mean ocular perfusion pressure correlated positively with end diastolic velocity in the ophthalmic artery (R = 0.66, P =.002) and central retinal artery (R = 0.74, P <.0001) and negatively with resistivity index in the ophthalmic artery (R = -0.70, P =.001) and central retinal artery (R = -0.62, P =.003) in patients with deteriorating glaucoma. Such correlations did not occur in patients with glaucoma with stable visual fields or in normal subjects. The correlations were statistically significantly different between the study groups (parallelism of regression lines in an analysis of covariance model) for end diastolic velocity (P =.001) and resistivity index (P =.0001) in the ophthalmic artery, as well as for end diastolic velocity (P =.0009) and resistivity index (P =. 001) in the central retinal artery. CONCLUSIONS: The present findings suggest that alterations in ocular blood flow regulation may contribute to the progression in glaucomatous damage.

Ocular blood flow alteration in glaucoma is related to systemic vascular dysregulation.

AIMS: To investigate the source of ocular blood flow alterations in glaucoma. METHODS: In 56 patients with open angle glaucoma, blood flow parameters were obtained from both eyes in the ophthalmic and central retinal artery by means of colour Doppler imaging, as well as in the choroidal circulation and the neuroretinal rim of the optic nerve by means of laser Doppler flowmetry. Based on these haemodynamic parameters, a cluster analysis (two groups) was performed and differences with regard to risk factors were assessed between clusters. RESULTS: Ocular blood flow data in the two clusters indicated that the two groups (cluster 1 = 26 patient with higher blood flow values; cluster 2 = 30 patients with lower blood flow values) differed mainly in choroidal and optic nerve blood flow. No differences in sex distribution, propensity to have normal tension glaucoma, age, endothelin-1 plasma levels, visual field damage, intraocular pressure, or systemic blood pressure parameters were observed between the two clusters. However, 12 patients (46%) from the cluster with high ocular blood flow values showed a vasospastic response in nailfold capillaroscopy, while such a response was observed in 24 patients (80%) of the cluster with low ocular blood flow values. This difference in vasospastic propensity was statistically significant (p = 0.0121). CONCLUSIONS: Ocular blood flow alterations in glaucoma patients seem, at least partly, to be related to a systemic vascular dysregulation.