Diurnal fluctuation of ocular blood flow parameters in patients with primary open-angle glaucoma and healthy subjects.

BACKGROUND/AIMS: To investigate the fluctuations of ocular blood flow parameters over 13 h in patients with primary open-angle glaucoma (POAG) and in healthy eyes, and to relate these fluctuations with variations in intraocular pressure (IOP) and mean ocular perfusion pressure (OPP). METHODS: 15 patients with POAG and 15 control subjects were included. Measurements of systemic blood pressure (SBP), fundus pulsation amplitude (FPA), choroidal blood flow (CHBF), optic nerve head blood flow (ONHBF) and IOP were performed at 08:00, 12:00, 17:00 and 21:00. OPP was calculated from IOP and SBP. The coefficient of variation (CV) was calculated for all individual parameters to assess their variability. RESULTS: The time response of the ocular haemodynamic variables was not different between the groups. Most of the outcome variables showed significantly larger fluctuations in patients with POAG compared with healthy controls (CV: FPA: 0.085 (SD 0.033) vs 0.054 (0.029), p = 0.012; CHBF: 0.082 (0.030) vs 0.052 (0.023), p = 0.005; ONHBF: 0.086 (0.044) vs 0.059 (0.032), p = 0.063). These changes were not associated with OPP or IOP. Changes over time correlated among the different ocular haemodynamic outcome measures in patients with POAG (r = 0.678, r = 0.557, r = 0.545; p<0.04) but not in the control subjects (r = 0.336, r = -0.227, r = -0.130; p>0.22). CONCLUSION: Patients with POAG show a larger diurnal fluctuation of ocular blood flow parameters. These fluctuations appear not to be related to a higher statistical error of the applied measurement techniques in POAG patients. These data support the hypothesis that POAG is associated with vascular dysregulation.

Effects of high-dose prednisolone on optic nerve head blood flow in patients with acute optic neuritis.

BACKGROUND: In this study, patients with optic neuritis were treated with high-dose prednisolone. Little information is available about the effects of this treatment on ocular blood flow. We set out to investigate the effects of high-dose prednisolone on optic nerve head (ONH) blood flow in patients with acute optic neuritis. METHODS: Thirteen patients with acute optic neuritis were included in the study. 1000 mg of prednisolone was infused intravenously over 30 minutes on 3 consecutive days. On each study day, ONH blood flow was measured using laser Doppler flowmetry. The ocular hemodynamic measurements were performed on the unaffected eye of the patients with unilateral acute optic neuritis before and immediately after cessation of the infusion. Intraocular pressure (IOP) and systemic blood pressure was measured before and after the infusion on each study day. Data was analyzed using a repeated measures ANOVA model. RESULTS: Prednisolone increased ONH blood flow in the patients under study (p = 0.04), although the effects were in generally small. No significant change in mean arterial pressure (p = 0.70) or IOP (p = 0.20) could be detected in the patients treated with high-dose prednisolone. CONCLUSIONS: A small but significant increase in ONH blood flow resulted from infusion of high-dose prednisolone. Further studies are required to investigate whether this effect contributes to the therapeutic efficacy of cortisone in patients with optic neuritis.

Effect of dorzolamide and timolol on ocular blood flow in patients with primary open angle glaucoma and ocular hypertension.

BACKGROUND: There is evidence that perfusion abnormalities of the optic nerve head are involved in the pathogenesis of glaucoma. There is therefore considerable interest in the effects of topical antiglaucoma drugs on ocular blood flow. A study was undertaken to compare the ocular haemodynamic effects of dorzolamide and timolol in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT). METHODS: One hundred and forty patients with POAG or OHT were included in a controlled, randomised, double blind study in two parallel groups; 70 were randomised to receive timolol and 70 to receive dorzolamide for a period of 6 months. Subjects whose intraocular pressure (IOP) did not respond to either of the two drugs were switched to the alternative treatment after 2 weeks. Scanning laser Doppler flowmetry was used to measure blood flow in the temporal neuroretinal rim and the cup of the optic nerve head. Pulsatile choroidal blood flow was assessed using laser interferometric measurement of fundus pulsation amplitude. RESULTS: Five patients did not respond to timolol and were changed to the dorzolamide group, and 18 patients changed from dorzolamide treatment to timolol. The effects of both drugs on IOP and ocular perfusion pressure were comparable. Dorzolamide, but not timolol, increased blood flow in the temporal neuroretinal rim (8.5 (1.6)%, p<0.001 versus timolol) and the cup of the optic nerve head (13.5 (2.5)%, p<0.001 versus timolol), and fundus pulsation amplitude (8.9 (1.3)%, p<0.001 versus timolol). CONCLUSIONS: This study indicates augmented blood flow in the optic nerve head and choroid after 6 months of treatment with dorzolamide, but not with timolol. It remains to be established whether this effect can help to reduce visual field loss in patients with glaucoma.

Twelve hour reproducibility of choroidal blood flow parameters in healthy subjects.

AIMS/BACKGROUND: To investigate the reproducibility and potential diurnal variation of choroidal blood flow parameters in healthy subjects over a period of 12 hours. METHODS: The choroidal blood flow parameters of 16 healthy non-smoking subjects were measured at five time points during the day (8:00, 11:00, 14:00, 17:00, and 20:00). Outcome parameters were pulsatile ocular blood flow as assessed by pneumotonometry, fundus pulsation amplitude as assessed by laser interferometry, blood velocities in the opthalmic and posterior ciliary arteries as assessed by colour Doppler imaging, and choroidal blood flow, volume, and velocity as assessed by fundus camera based laser Doppler flowmetry. The coefficient of variation and the maximum change from baseline in an individual were calculated for each outcome parameter. RESULTS: None of the techniques used found a diurnal variation in choroidal blood flow. Coefficients of variation were within 2.9% and 13.6% for all outcome parameters. The maximum change from baseline in an individual was much higher, ranging from 11.2% to 58.8%. CONCLUSIONS: These data indicate that in healthy subjects the selected techniques provide adequate reproducibility to be used in clinical studies. Variability may, however, be considerably higher in older subjects or subjects with ocular disease. The higher individual differences in flow parameter readings limit the use of the techniques in clinical practice. To overcome problems with measurement validity, a clinical trial should include as many choroidal blood flow outcome parameters as possible to check for consistency.

Choroidal blood flow and arterial blood pressure.

PURPOSE: Untreated hypertension is associated with ocular complications and is a risk factor for the development and progression of vascular ocular pathologies. We set out to investigate the association between systemic blood pressure and choroidal blood flow. METHODS: All subjects were male non-smokers, who did not receive any medication and had normal or slightly elevated blood pressure (systolic blood pressure < or = 160 mmHg; diastolic blood pressure < or = 100 mmHg). The association between systemic blood pressure and fundus pulsation amplitude, a measure of pulsatile choroidal blood flow, was investigated in 318 volunteers. In addition, the association between systemic blood pressure and blood flow velocities in the posterior ciliary arteries supplying the choroid was investigated in these subjects. RESULTS: Ocular fundus pulsation amplitude (r = 0.252; P < 0.001) and mean flow velocity in the posterior ciliary arteries (r = 0.346, P < 0.001) were significantly associated with mean arterial pressure. The correlation of ocular haemodynamic variables with systolic and diastolic blood pressure was in the same range. CONCLUSIONS: Our data indicate a small, but significant increase in choroidal blood flow with increasing blood pressure.

Ocular hyperperfusion following onset of intensified insulin therapy is inversely correlated with plasma endothelin-1 in Type I diabetes.

AIMS/HYPOTHESIS: It has been reported that improvement of metabolic control by intensified insulin therapy in patients with Type I (insulin-dependent) diabetes mellitus is associated with alterations in ocular blood flow. We hypothesized that these changes in ocular blood flow could be associated with alterations of plasma insulin, glucose or endothelin concentration. METHODS: In 16 patients with Type I diabetes ocular haemodynamic parameters were assessed daily during the first 5 days of institution of intensified insulin therapy and plasma concentrations of glucose, insulin, and endothelin-1 plasma were measured. Retinal white blood cell flux was estimated with the blue field entoptic technique. Pulsatile choroidal blood flow was assessed by laser interferometric measurement of fundus pulsation amplitude. RESULTS: Retinal white blood cell flux ( p=0.0015) and ocular fundus pulsation amplitude ( p<0.001) increased during institution of strict metabolic control. Changes in ocular haemodynamic variables were inversely correlated with concentrations of plasma ET-1, but not with that of insulin or glucose. CONCLUSIONS/INTERPRETATION: These data indicate that institution of improved metabolic status is paralleled by rapid changes in the production of ET-1, which could in turn affect ocular perfusion.

Unilateral light-dark transitions affect choroidal blood flow in both eyes.

There is recent evidence that the perfusion of the choroid changes during dark-light transitions. We set out to investigate this response in more detail and to elucidate possible mechanisms involved in this process. For this purpose, the effect of dark-light transitions on choroidal perfusion was studied in healthy subjects. Choroidal blood flow and ocular fundus pulsation amplitude were measured as indices of choroidal perfusion during dark-light transitions using laser Doppler flowmetry and laser interferometry, respectively. In the first experiment, subjects were first kept in room light for 20 min, then light conditions were changed to darkness for 20 min, and thereafter, subjects were exposed to room light again. Both choroidal parameters decreased (-12% to -14%) during darkness but returned to baseline after the final room light period. In the second experiment, the index eye underwent the same procedure, whereas the contralateral eye was kept in light throughout the experiment. Choroidal haemodynamic parameters in the index eye reacted in a way comparable to that seen in the first experiment. The eye that was kept in light also reacted, but the effect tended to be less pronounced than that seen in the index eye (-8% to -10%). The observation that choroidal blood flow in both eyes reacts during unilateral light-dark transitions indicates that choroidal perfusion rate is adapted to retinal illumination conditions by neural control mechanisms.

Retinal blood flow and systemic blood pressure in healthy young subjects.

BACKGROUND: The aim of the present study was to investigate the association between systemic blood pressure and retinal blood flow in healthy young subjects. METHODS: Three independent study cohorts were included. A cross-sectional study was performed in 420 young male subjects with systolic blood pressure < 160 mmHg and diastolic blood pressure <100 mmHg. Retinal white blood cell flux (n=210) and blood velocity in the central retinal artery (n=210) were measured. In addition, a longitudinal study was performed in 40 young male subjects in whom retinal and systemic haemodynamic parameters were measured thrice within 6 weeks. Retinal white blood cell flux was measured with the blue-field entoptic technique. Blood flow velocity in the central retinal artery was measured by means of colour Doppler imaging. RESULTS: Retinal white blood cell flux (r=0.262; P<0.001) and mean flow velocity in the central retinal artery (r=0.174, P=0.010) were significantly associated with mean arterial pressure in the cross-sectional study. In the longitudinal study retinal white blood cell flux and mean flow velocity in the central retinal artery were also correlated with systemic blood pressure. CONCLUSIONS: Our data indicate a slight but significant increase in retinal blood flow with blood pressure. Whether this is of clinical relevance in eye diseases with altered retinal perfusion, such as diabetic retinopathy, remains to be established.

Health related quality of life in patients with long-standing insulin dependent (type 1) diabetes mellitus: benefits of regular physical training.

BACKGROUND AND AIMS: Regular exercise is recommended to diabetic patients in addition to dietary restrictions and drug therapy. We have studied whether health related quality of life (HRQOL) can be improved by a regular physical training program. METHODS: 23 otherwise healthy patients with history of type 1 diabetes for 20 +/- 10 years were included. 15 patients (age: 41 +/- 2 years) participated in an aerobic physical training program over 4 months and 8 patients (33 +/- 11 years) served as a control group. HRQOL was assessed by a validated questionnaire (MOS SF-36). Tests were carried out at baseline and after 4 months. RESULTS: Physical training increased peak oxygen uptake (VO2max) by 27 +/- 13% after 4 months (p = 0.04) in the training group. There was no significant change in hand or leg isometric muscle strength. All HRQOL scales improved in the training group with significantly higher (p < 0.04) Social Functioning and Vitality scores, respectively. Moreover, insulin requirements decreased during physical training program (p < 0.05). CONCLUSIONS: Our data indicate that physical exercise training in patients with type I diabetes mellitus improves metabolic control and various aspects of HRQOL. Besides enhanced cardiorespiratory capacity, this is an important subjective benefit in patients with longstanding insulin dependent (type 1) diabetes mellitus.