Scanning Laser Doppler Flowmetry Research Articles

Effect of Dorzolamide and Timolol on Ocular Pressure: Blood Flow Relationship in Patients with Primary Open-Angle Glaucoma and Ocular Hypertension

The authors have reported previously that a study population, consisting of patients with glaucoma and ocular hypertension, is characterized by an impaired association between ocular blood flow parameters and systemic blood pressure, indicative of abnormal autoregulation. Here they report on the effects of dorzolamide and timolol on ocular pressure/flow relationships to test the hypothesis that these drugs improve autoregulation. One hundred forty patients with primary open-angle glaucoma or ocular hypertension were included in a clinical trial in a controlled, randomized double-masked study in two parallel groups. Seventy patients were randomly assigned to receive timolol, and 70 patients were randomly assigned to receive dorzolamide for a 6-month period. 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. The association between blood flow parameters and systemic blood pressure was compared before and after the 6-month treatment period. Before treatment a significant association was observed between ocular blood flow parameters and systemic blood pressure in both parallel groups (r = 0.23-0.42). All regression lines between ocular hemodynamic parameters and systemic blood pressure were less steep after treatment with either dorzolamide or timolol (r = 0.03-0.24). The present study indicates that intraocular pressure reduction with timolol or dorzolamide is associated with normalization of the ocular pressure/flow relationship. Whether this is related to the beneficial effects of IOP-lowering therapy in glaucoma remains to be established. (ClinicalTrials.gov number, NCT00991822.).

Macular blood flow measured by blue‐field entoptoscopy and Heidelberg retinal flowmetry: comparison of two techniques in type 1 diabetes women during pregnancy

This study compared macular capillary leucocyte velocity values measured with a psychophysical blue-field entoptic simulation (BFS) technique and confocal scanning laser Doppler flowmetry. A cross-sectional study was performed where macular capillary leucocyte velocity was measured by BFS using an Oculix BFS-2000 V2.1 psychophysical system and by confocal scanning laser Doppler flowmetry using Heidelberg retinal flowmetry (HRF) in 35 type 1 diabetes women during the second trimester. The macular leucocyte velocities measured with BFS correlated significantly with the 50th percentile (r = 0.345, p = 0.042, n = 35, Spearman's non-parametric correlation), the 75th percentile (r = 0.432, p = 0.009) and the 90th percentile (r = 0.373, p = 0.027) of HRF flow values during the second trimester. However, there was no correlation between BFS velocity and the 25th percentile of HRF measurements. Blue-field simulation is known to be an experimental technique that provides a quantitative measure of flow in the perifoveal capillary network. By contrast, HRF imaging reflects quantitative, multispectral, objective and non-invasive measurements in a two-dimensional projection of a three-dimensional retinal capillary bed. Our study showed that BFS velocity was correlated with HRF values in a group of women with diabetes during pregnancy. The positive correlation between BFS and HRF values suggests that the psychophysical BFS and scanning laser-based HRF measure similar functions in the retina.

Wall-to-Lumen Ratio of Retinal Arterioles as a Tool to Assess Vascular Changes

The retina offers a beautiful and unique opportunity to visualize and examine the body’s microvasculature safely, repeatedly, quickly, and noninvasively in vivo. Retinal arterioles appear to undergo similar changes as cerebral and peripheral arterioles in hypertension, indicating that retinal arteriolar abnormalities mirror structural and functional microvascular changes elsewhere in end-organ tissues.1–4 Since the pioneering work by Keith et al5 in 1939, several studies have confirmed the prognostic significance of retinal vascular abnormalities on mortality attributed to a cardiovascular cause.5–7 However, although there is solid evidence for the prognostic significance of advanced retinopathy, the evidence of a prognostic impact of early retinal vascular abnormalities on cardiovascular risk stratification is less well established.1,8 It was suggested that methodological issues might be the cause for the lack of a solid evidence that early retinal vascular abnormalities are closely linked to cardiovascular risk.1,9 Therefore, much research effort over the last decade has focused on the development of new methodological approaches to enable more precise and reliable detection and evaluation of early retinal vascular abnormalities in hypertensive patients. A new approach focuses on retinal arteriolar structural parameters by using scanning laser Doppler flowmetry (SLDF) with automatic full-field perfusion imaging analyses (AFFPIAs).2,10 This approach allows the assessment of both the outer diameter (OD) and inner diameter (ID) of retinal arterioles in vivo and, thus, analyzes vascular remodeling of retinal arterioles by calculating wall:lumen ratio, wall thickness, and wall cross-sectional area (volume of wall per unit of length) of retinal arterioles. These methods do not need to determine diameter of retinal venules, which are also subject to changes in cardiovascular disease. This review introduces and describes this new methodology, explains the improved power of measuring retinal vascular changes, and discusses our recent findings using this tool. The idea of assessing the …

Wall-to-Lumen Ratio of Retinal Arterioles and Arteriole-to-Venule Ratio of Retinal Vessels in Patients with Cerebrovascular Damage

There is evidence that generalized retinal arteriolar narrowing, which can be measured by the arteriole-to-venule ratio (AVR) of retinal vessels, predicts cerebrovascular events. The wall-to-lumen ratio (WLR) and wall cross-sectional area (WCSA) of retinal arterioles reflect structural arteriolar parameters. The primary objective was to test the association between WLR and AVR in a distinct cohort of patients with cerebrovascular damage. In this cross-sectional study, 23 patients (57.5 +/- 9.4 years) with acute transitory ischemic attack or lacunar cerebral infarct were compared with two age-matched control groups: 83 subjects with essential hypertension (53.7 +/- 5.5 years) and 16 normotensive subjects (52.2 +/- 8.3 years). Retinal arteriolar parameters (WLR, WTH, and WCSA) were assessed in vivo with scanning laser Doppler flowmetry (SLDF). AVR and a qualitative evaluation of retinal vessels were obtained from digital retinal color photographs. The intima-media thickness (IMT) of the carotid artery was measured. WLR (0.44 +/- 0.1 vs. 0.34 +/- 0.1 vs. 0.30 +/- 0.1, P < 0.001) and carotid IMT (P < 0.05) were significantly greater in the cerebrovascular event group compared with normotensive subjects. WLR and WCSA were significantly higher in the cerebrovascular event group compared with subjects with mild arterial hypertension. AVR was similar in all three study groups (0.75 +/- 0.07 vs. 0.74 +/- 0.07 vs. 0.78 +/- 0.1, P = 0.18). The increase in WLR and WCSA of retinal arterioles, as well as in IMT in patients with cerebrovascular damage suggests vascular hypertrophy in the microvascular and macrovascular bed. The lack of association between AVR of retinal vessels and WLR of retinal arterioles may point to different stages of cerebrovascular disease and/or different pathophysiological changes in the arteriolar wall.

Correlation Among Choroidal, Parapapillary, and Retrobulbar Vascular Parameters in Glaucoma

To study and compare the correlation among choroidal, parapapillary, and retrobulbar vascular parameters in healthy subjects, glaucoma suspects, and open-angle glaucoma (OAG) patients. Prospective observational clinical study. The study included one randomly selected eye from 21 normal subjects, 30 glaucoma suspects based on optic disc appearance, and 22 OAG patients. The pulsatile ocular blood flow (POBF), a measure of choroidal blood flow, was assessed using ocular blood flow analyzer whereas parapapillary blood flow and blood velocity of retrobulbar blood vessels were measured using scanning laser Doppler flowmetry and color Doppler imaging, respectively. All vascular parameters along with blood pressure and intraocular pressure measurements were obtained within a 2-hour period. Univariate regression analyses were used to evaluate the correlation of POBF values with parapapillary blood flow values, retrobulbar blood flow velocities, and resistive index, which represents vascular resistance, in each group. Two multiple linear regression models were created based on results of univariate analyses and included POBF, mean parapapillary blood flow, age, and mean ocular perfusion pressure; and POBF, temporal short posterior ciliary artery resistive index, age, and mean ocular perfusion pressure. POBF was significantly associated with parapapillary blood flow (r2 = 0.54; P < .001, positive correlation) and temporal short posterior ciliary artery resistive index (r2 = 0.39; P < .001, negative correlation) in normal subjects. Results were consistent when corrected for age, intraocular pressure, and blood pressure parameters. POBF values did not correlate with parapapillary blood flow values or temporal short posterior ciliary artery resistive index in glaucoma suspects or OAG patients. The relationships of POBF with parapapillary blood flow and calculated retrobulbar vascular resistance differs among normal subjects, glaucoma suspects, and OAG patients. This provides further evidence of vascular dysregulation in OAG.

Blood flow in the peripapillary retina in exfoliation glaucoma

The aim of this article is to study peripapillary retinal blood flow in patients with progressive and stable exfoliation glaucoma (ExG). Fifty-eight eyes with ExG were included; 25 of them had progressive and 33 stable glaucoma. Retinal blood flow in the peripapillary retina was measured with scanning laser Doppler flowmetry. Acquired flow maps were analysed with the automatic full-field perfusion image analyser. Multiple logistic regression was used to model progression of glaucoma. Mean retinal flow (MF; correlation coefficient, P-value; R = 0.36, P = 0.006) and retinal minimum diastolic flow (R = 0.33, P = 0.011) were positively correlated with visual field mean defect (MD). Factors associated with progressive glaucoma were mean intraocular pressure (OR = 1.198 for each mmHg; P = 0.050) and visual field MD (OR = 1.134 for each dB; P = 0.013). Age (P = 0.35), MF (P = 0.58), or presence of cardiovascular disease (P = 0.17) were not associated with glaucoma progression. No difference in peripapillary retinal blood flow between progressive and stable ExG could be found.

Measuring and interpreting ocular blood flow and metabolism in glaucoma

There is a growing body of evidence suggesting that vascular dysfunction is related to several prominent ophthalmic diseases, including glaucoma.The vast majority of studies providing data on ocular circulation and disease pathophysiology use a relatively small number of complicated ocular blood flow imaging techniques. Although these imaging technologies are not commonly used in clinical settings, understanding the medical literature characterizing ocular blood flow requires familiarity with their methodology and function. This review highlights the imaging technologies most commonly used to investigate ocular blood flow, including color Doppler imaging, confocal scanning laser ophthalmoscopic angiography with fluorescein and indocyanine green dye, Canon laser blood flowmetry, scanning laser Doppler flowmetry, and retinal photographic oximetry. Each imaging technique's ability to define vascular function and reveal pathology is discussed as are limitations inherent to each technology. The ultimate goal of this review is to provide the physician with a clinically relevant foundation for differentiating the various ocular blood flow outcome measures often presented in the literature and determine how they are related to ocular health and disease.

The effects of raloxifene hydrochloride on ocular hemodynamics and visual function

To assess the comprehensive effects of raloxifene hydrochloride on retinal, choroidal and retrobulbar hemodynamics and on visual function in post-menopausal women. Twenty-four post-menopausal women (age 55 +/- 3.8 years) were recruited for this cross-sectional study: 12 received placebo and 12 received raloxifene hydrochloride 60 mg once a day for 3 months. Baseline measurements of both groups included heart rate (HR), blood pressure (BP), visual acuity, contrast sensitivity and intraocular pressure (IOP) for both eyes. A comprehensive ocular blood flow (OBF) assessment was obtained for each patient in a randomly chosen study eye. Retinal blood flow data was obtained using confocal scanning laser Doppler flowmetry [Heidelberg Retinal Flowmeter (HRF)]. Color Doppler imaging (CDI) was used to assess retrobulbar hemodynamics in the ophthalmic, central retinal, short nasal and temporal posterior ciliary arteries. Baseline vision and hemodynamics in post-menopausal subjects were compared using paired Student's t tests, and the percentage change in baseline versus 3-month parameters was analyzed. There were no statistically significant differences between 3 months of raloxifene therapy and placebo in terms of age, HR, arterial or mean BP, visual acuity, contrast sensitivity, IOP or retinal or retrobulbar blood flow. Raloxifene therapy at 60 mg/day had no clinically significant impact on BP, IOP or OBF in post-menopausal women.

A comparative study of the effects of brinzolamide and dorzolamide on retinal oxygen saturation and ocular microcirculation in patients with primary open-angle glaucoma

Aims:To assess the effects of brinzolamide and dorzolamide on ocular haemodynamics and retinal oxygen saturation in patients with primary open-angle glaucoma (OAG).Methods:Fifteen patients with OAG were evaluated in a randomised,...

Effects of angiotensin II type 1-receptor blockade on retinal endothelial function

Hypercholesterolemia is an important risk factor for atherosclerotic vascular disease including stroke. Low-density lipoprotein-cholesterol may induce upregulation of angiotensin II type 1 (AT1)-receptors and their activation plays a pathogenetic role in atherosclerosis, possibly via enhanced breakdown of nitric oxide. We tested whether AT1-receptor blockade improved endothelial function of the retinal vasculature in normocholesterolemic and hypercholesterolemic subjects. Thirty-one hypercholesterolemic and 17 normocholesterolemic subjects were randomly assigned to treatment with irbesartan and placebo in a double-blind crossover study. Retinal capillary flow was measured using scanning laser Doppler flowmetry. Diffuse luminance flicker was applied to provoke vasodilation that is in part nitric oxide dependent. Flicker-induced increases in retinal capillary flow were similar between hypercholesterolemic and normocholesterolemic subjects. In contrast to placebo, treatment with irbesartan led to a significant reduction of blood pressure, in our patients with normal blood pressure values. Therefore we divided our study cohort according to the median blood pressure reduction in response to irbesartan. Flicker-induced increases in retinal capillary flow were substantially higher in subjects with a systolic blood pressure reduction above median (> 6 mmHg) than in those with a reduction below median (<or=6 mmHg) (16.2 +/- 16% versus 6.88 +/- 11%; P = 0.042). AT1-receptor blockade with irbesartan improves endothelial function of the retinal vasculature, taken as a model of cerebral circulation.

REDUCED CHOROIDAL BLOOD FLOW CAN INDUCE VISUAL FIELD DEFECT IN OPEN ANGLE GLAUCOMA PATIENTS WITHOUT INTRAOCULAR PRESSURE ELEVATION FOLLOWING ENCIRCLING SCLERAL BUCKLING

To determine the cause of the progressive glaucomatous visual field defects in three patients after an encircling scleral buckle for a rhegmatogenous retinal detachment (RRD). Scanning laser Doppler flowmetry and visual field tests were performed on three cases with unilateral progressive visual field defect after an encircling scleral buckling for a RRD. Similar measurements were made after the buckle was removed. After implanting the scleral buckle, the intraocular pressure was normal and chamber angle was open. The blood flow in the neuroretinal rim of the optic disk was lower than that in the healthy fellow eye. After removing the buckle, the blood flow improved to normal levels and a further worsening of the visual field was not detected. These results suggest that an encircling scleral buckle may impair choroidal circulation and lead to visual field defects similar to eyes with normal tension glaucoma.

The effects of dorzolamide 2% and dorzolamide/timolol fixed combination on retinal and optic nerve head blood flow in primary open-angle glaucoma patients

To compare the effect of dorzolamide hydrochloride 2%, timolol maleate 0.5%, and their fixed combination on intraocular pressure (IOP)and retinal and optic nerve head haemodynamics in primary open-angle glaucoma patients. Twenty-eight patients with early moderate glaucomatous damage treated with β-blockers (>6 months) with IOP values ranging from 18 to 22 mmHg at trough participated in this trial. After a 4-week washout period,patients were randomised in two groups: group I started with dorzolamide 2% monotherapy and group II with timolol 0.50% monotherapy for 4 weeks. After this period, both groups switched to dorzolamide/timolol fixed combination for 4 weeks. IOP, ocular diastolic perfusion pressure, heart rate, and Scanning Laser Doppler Flowmetry measurements at the peripapillary retina and neuroretinal rim were taken at T0 (enrolment), T1 (wash out), T2(monotherapy), and T3 (dorzolamide/timolol).Data were compared between different study times. Statistical analysis was conducted using a paired t-test. Between T1 and T3, IOP decreased significantly in group I (-21.40%) (P<0.001)and in group II (-21.25%) (P<0.001). At the same time intervals, blood flow increased significantly at rim level for group I (+30.03%)(P<0.05) and also when all patients were considered (rim +20.81%) (P<0.05). Between T1 and T3, we also observed a significant increase of ODPP in group I (+7.24%) (P<0.01)and in group II (+6.08%) (P<0.05) and when all patients were considered (+6.71%)(P<0.001) [corrected]. Dorzolamide/timolol fixed combination increased blood flow significantly at the neuroretinal rim showing a combination of hypotensive and haemodynamic effects.

Reliability of Different Image Analysis Methods for Scanning Laser Doppler Flowmetry

Purpose: To assess reliability and reproducibility of different analysis methods for retinal capillary flow, volume, and velocity from scanning laser Doppler flowmetry (SLDF) topography. Material and Methods: SLDF topography analysis using the default retinal flowmeter (HRF) were compared to that using automatic full-field perfusion image analyzer (AFFPIA) and quantified as intraclass correlation coefficients (ICC). Results: The AFFPIA full-field method had the highest reliability, with ICC 0.99 for capillary flow. The reproducibility using the AFFPIA full-field method was high ICC 0.74 for capillary flow. Conclusions: The AFFPIA full-field method is highly reliable and superior to the default HRF software.

Variability of ocular perfusion measurements in glaucoma and healthy subjects

Abstract Purpose: Variability is a major problem in ocular blood flow measurements. It is an important determinant of sample size in clinical trials and may limit clinical usefulness if it is too high. We set out to compare the short‐term reproducibility of blood flow parameters assessed with scanning laser Doppler flowmetry and laser interferometric measurement of fundus pulsation between healthy young subjects and glaucoma patients. Methods: Measurements in 140 healthy male non‐smoking subjects and 140 patients with primary open angle glaucoma were included in this analysis. From two consecutive measurements performed within 5 minutes the coefficient of variation in an individual was calculated for each outcome parameter. These included the fundus pulsation amplitude (FPA), the flow, volume and velocity in the rim and the cup. Results: Mean coefficients of variation were between 3.2% and 23.8 % for all outcome parameters in healthy subjects and between 4.9% and 34.3% in the patients. FPA showed the highest reproducibility although individual coefficients of up to 22.5% and 34.7% were observed in healthy subjects and glaucoma patients, respectively. With scanning laser Doppler flowmetry velocity was better reproducible than volume or flow. Individual coefficients of variation for flow values were as high as 87.5% in healthy subjects and 132.2% in glaucoma/ocular hypertension patients. Conclusions: Our data indicate that in healthy subjects the selected techniques provide better reproducibility than in patients with ocular disease. This needs to be considered in sample size calculation for clinical trials. In addition, the high individual differences in flow parameter readings observed in some subjects limit the use of the techniques in clinical practice.

Increased Wall:Lumen Ratio of Retinal Arterioles in Male Patients With a History of a Cerebrovascular Event

Arterial hypertension is a major risk factor for stroke, and retinal vessels can be regarded as a mirror of the cerebral vasculature. Whether vascular remodeling of retinal arterioles with ageing and hypertension plays a role in cerebrovascular risk stratification has not yet been adequately addressed. In study 1, retinal arteriolar structure was assessed in 182 normotensive volunteers and 117 patients with essential hypertension. In study 2, we compared retinal arteriolar structure among 74 normotensive volunteers, 47 patients with treated essential hypertension, and 18 subjects with a history of a cerebrovascular event. Retinal arteriolar structure was assessed using scanning laser Doppler flowmetry and automatic full-field perfusion imaging analysis. In study 1, wall:lumen ratio of retinal arterioles revealed a significant correlation with age (r=0.198; P=0.001). In study 2, wall:lumen ratio was highest in patients with a history of a cerebrovascular event compared with treated hypertensive and normotensive subjects (0.46+/-0.08, 0.36+/-0.14, and 0.35+/-0.12; P=0.007). When the treated group with hypertension was divided into 2 subgroups according to the quality of blood pressure control, patients with poor blood pressure control showed higher wall:lumen ratio than subjects with good blood pressure control (0.40+/-0.13 versus 0.31+/-0.13; P=0.025). Thus, assessment of wall:lumen ratio of retinal arterioles emerged as an attractive tool to identify treated patients with hypertension with increased cerebrovascular risk.

MORPHOMETRIC AGE-RELATED EVALUATION OF SMALL RETINAL VESSELS BY SCANNING LASER DOPPLER FLOWMETRY

Measurement of the retinal vessel wall thickness may contribute to the diagnosis of microvascular diseases. We present a methodical approach to calculate these alterations and to determine age-related differences. One hundred fifty-three subjects without eye or internal diseases (mean age +/- SD, 47.6 +/- 14.9 years) underwent measurement of the retinal temporal superior artery and vein by scanning laser Doppler flowmetry (Heidelberg retina flowmeter). We calculated the difference between the diameter of reflectivity and the Doppler signal (Delta[VD-FD]/2) and determined a "vessel wall index" (VWI) by normalization of Delta(VD-FD)/2 for age and vessel diameter. Delta(VD-FD)/2 correlated with vessel diameter (artery, r = +0.60, P < 0.001; vein, r = +0.49, P<0.001) and age (artery, r = +0.19, P = 0.02; vein, r = +0.27, P = 0.001) but not with sex, if controlled for the other variables each. The venous, but not the arterial, vessel diameter correlated with age (r = +0.18, P = 0.02), if controlled for sex. The relative statistical weight of these empirical contributions to the variation observed in Delta(VD-FD)/2 was 36.5% (P < 0.001, artery) and 21.7% (P< 0.001, vein), and that of age was 3.6% (P = 0.02, artery) and 7.3% (P = 0.001, vein). The limit value of VWI to pathologic changes (80th percentile) was 1.25 microm/y (artery) and 1.31 microm/y (vein). Delta(VD-FD)/2 normalized for vessel diameter correlated with the 10-year categories of age (artery, r = +0.196, P = 0.017; vein, r = +0.250, P = 0.002). In a group of subjects aged 21 years to 70 years, we detected an increase of Delta(VD-FD)/2 in the retinal temporal superior artery and vein with age.

Relationship Between Central Corneal Thickness and Changes of Optic Nerve Head Topography and Blood Flow After Intraocular Pressure Reduction in Open-angle Glaucoma and Ocular Hypertension

To investigate changes in optic nerve head topography and blood flow after therapeutic intraocular pressure reduction and to correlate them with central corneal thickness. Sixteen patients with open-angle glaucoma and 16 patients with ocular hypertension underwent Heidelberg retina tomography and scanning laser Doppler flowmetry in 1 eye before and at least 2 months after a mean 35% sustained therapeutic reduction in intraocular pressure. Patients were assigned to a thin or thick group based on their median central corneal thickness. Compared with 16 patients with thick corneas (mean +/- SD central corneal thickness, 587 +/- 31 microm), the 16 patients with thin corneas (518 +/- 32 microm) had greater reductions in mean (36 +/- 32 vs 4 +/- 36 microm, P = .003) and in maximum cup depth (73 +/- 107 vs 4 +/- 89 microm, P = .02). These changes were not statistically significantly different between the patients with open-angle glaucoma and those with ocular hypertension. Smaller mean +/- SD improvements in neuroretinal rim blood flow were seen in patients with thinner corneas compared with those with thicker corneas (35 +/- 80 vs 110 +/- 111 arbitrary units, P = .04). Patients with open-angle glaucoma and ocular hypertension with thinner corneas show significantly greater shallowing of the cup, a surrogate marker for lamina cribrosa displacement (compliance), and smaller improvements of neuroretinal rim blood flow after intraocular pressure reduction.

A Comparative Analysis of the Effects of the Fixed Combination of Timolol and Dorzolamide Versus Latanoprost Plus Timolol on Ocular Hemodynamics and Visual Function in Patients with Primary Open-Angle Glaucoma

The aim of this study was to assess the effects of fixed combination of timolol and dorzolamide and latanoprost plus timolol on retinal, choroidal, and retrobulbar hemodynamics and visual function in primary open-angle glaucoma (OAG) subjects. Sixteen (16) OAG patients (age, 63.5 +/- 10.8 years; 9 male) were evaluated in a randomized, crossover, double-blind study design after 4 weeks of treatment of latanoprost with timolol and fixed combination of timolol and dorzolamide. After randomization, 9 right eyes and 7 left eyes were included in the hemodynamic portion of the study. Measurements included: adverse events check, visual acuity, contrast sensitivity, blood pressure, heart rate, intraocular pressure (IOP), and fundus examination. Ocular blood flow was assessed using confocal scanning laser Doppler flowmetry, color Doppler imaging, and scanning laser ophthalmoscopy. Both therapies were effective at lowering IOP, whereas there was no statistically significant difference between latanoprost plus timolol and the fixed combination of timolol and dorzolamide (13.9% and 12.2% reduction, respectively; P = 0.5533). Fixed combination of timolol and dorzolamide significantly increased central retinal artery end diastolic blood flow velocity (P = 0.0168) and lowered resistance to flow (P = 0.0279). Temporal posterior ciliary artery peak systolic and end diastolic velocities were significantly increased with the fixed combination of timolol and dorzolamide (P = 0.0125 and 0.0238, respectively). Latanoprost plus timolol had no significant effects on ocular blood flow during 4 weeks of treatment. There were no statistically significant differences in adverse events, blood pressure, heart rate, visual acuity, contrast sensitivity scanning laser ophthalmoscopy, or Heidelberg Retinal Flowmeter for any treatment period. Fixed combination of timolol and dorzolamide therapy might increase blood flow in OAG patients while attaining a similar IOP reduction compared to latanoprost plus timolol. Visual function, however, was not different in this short-term comparison between the two treatments.

Hemorheologic Abnormalities Associated with HIV Infection: In Vivo Assessment of Retinal Microvascular Blood Flow

To evaluate retinal microvascular blood flow in human immunodeficiency virus (HIV)-infected individuals using scanning laser Doppler flowmetry (SLDF) and to seek correlations between flow and various laboratory measures that may predict alterations in flow. The Heidelberg Retina Flowmeter and SLDF software were used to acquire in vivo retinal blood flow data from 24 HIV-infected individuals and 16 HIV-negative control subjects. In each subject, separate scans were performed in each of six retinal regions: nasal parapapillary retina; macula; and the superior, nasal, inferior, and temporal periphery. Erythrocyte aggregation (assessed in vitro by a fully automatic erythrocyte aggregometer and by zeta sedimentation ratio [ZSR, a hematocrit-independent sedimentation rate]), serum fibrinogen level, plasma viscosity, and leukocyte rigidity (assessed in vitro with a cell transit analyzer) were compared with flow in selected regions. Flow was significantly higher in the periphery (superior, nasal, inferior, temporal) than in the posterior retina (nasal parapapillary retina, macula). Flow was highest in the temporal periphery for both HIV-infected subjects and control subjects. Flow in the posterior retina was significantly lower in HIV-infected subjects than in control subjects (P < 0.0001). Among HIV-infected individuals, flow in the macula correlated negatively with ZSR (r = -0.397, P = 0.0547) and leukocyte rigidity (r = -0.505, P = 0.0119). Microvascular blood flow in the posterior retina is reduced in HIV-infected individuals. Both increased erythrocyte aggregation and increased leukocyte rigidity contribute to this hemorheologic abnormality.

Nimodipine Plasma Concentration and Retinal Blood Flow in Healthy Subjects

Calcium antagonists are strong vasodilators, and nimodipine is known to improve cerebral blood flow. The purpose of this study was to measure retinal blood flow and nimodipine plasma concentrations during repeated oral dosing. In a double-blind, two-way, crossover study, 20 healthy subjects (mean age, 22.8 +/- 3.7 years) underwent examination of retinal perfusion and nimodipine plasma concentrations. In a placebo-controlled fashion, nimodipine was orally administered at a dosage of 30 mg three times a day for two periods of 5 days including a 9-day washout interval. At days 1, 5, 15, and 19, plasma concentrations of nimodipine and retinal perfusion were measured 11 times within 3 hours. Stereoselective analysis of nimodipine plasma concentrations was performed with the use of liquid chromatography-tandem mass spectrometry. Scanning laser Doppler flowmetry was used to measure the microcirculation of the juxtapapillary retina. Perfusion images were evaluated with the automatic full-field evaluation procedure (AFFPIA). Areas under the plasma concentration versus time curves were similar at day 1 and day 5 of nimodipine administration (t test: P = 0.64). Values of C(max) displayed a large interindividual variance and ranged from 0 ng/mL to 57.5 ng/mL. On average, maximum nimodipine plasma concentrations (C(max)) were 16.6 +/- 14.9 ng/mL and 12.0 +/- 10.3 ng/mL at day 1 and day 5, respectively (P = 0.068). They were observed at 81 +/- 50 and at 93 +/- 40 minutes (t(max)) after the administration of nimodipine at day 1 and day 5, respectively (P = 0.43). Retinal microcirculation was greater after nimodipine than after placebo, as reflected in significantly larger areas under the curves of percentage change in blood flow from baseline versus time (P < 0.01). The maximum increase of retinal blood flow from baseline was significantly more pronounced after nimodipine (28.5% +/- 14.4% and 39.6% +/- 21.4% at day 1 and day 5, respectively) than after placebo (20.5% +/- 16.8% and 31.9% +/- 14.6% at day 1 and day 5, respectively; P = 0.032). Oral nimodipine significantly increases retinal perfusion in healthy subjects.