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PURPOSE: To investigate the circulation of the optic nerve head and choroid in patients with glaucoma. METHODS: Laser Doppler flowmetry was used to determine optic nerve head relative blood velocity (ONVel), volume (ONVol), and flow (ONFlow) in 19 primary open-angle glaucoma patients and 15 age-matched healthy control subjects. In each subject, determinations were obtained from four sites on the neuroretinal tissue and from the center of the cup. A mean of the ONVel, ONVol, and ONFlow for these five measurement sites were calculated for each subject and defined as ONVel5, ONVol5, and ONFlow5. Circulatory parameters were correlated with measures of disease progression such as cup-to-disc ratio and Humphrey visual field indices. Measurements of relative choroidal blood velocity, volume, and flow were also obtained from the foveola. RESULTS: In glaucoma patients, mean ONFlow5 was significantly lower than in control subjects (24%; P = 0.001; independent, two-tailed Student's t-test). This decrease was caused by a significant decrease in ONVol5 (15%; P = 0.04) and a nonsignificant decrease in ONVel5 (10%; P = 0.07). In glaucomatous eyes, mean ONFlow was significantly reduced from normal, by 28% in the inferior temporal neuroretinal rim location (P = 0.001) and by 24% in the superior temporal location (P = 0.001). Although mean ONFlow was also decreased by 33% in the cup, the difference was not statistically significant after a Bonferroni correction was applied. No significant differences from normal were observed in the superior and inferior nasal rim tissues. In glaucoma patients, ONFlow5 was significantly and inversely correlated with the corrected pattern standard deviation (R = -0.53; P = 0.02) and with the cup-to-disc ratio (R = -0.65; P = 0.002). Choroidal blood flow measurements obtained in the foveola of glaucomatous eyes showed no statistically significant differences from normal. CONCLUSIONS: ONFlow5 is reduced by approximately 24% in glaucoma patients. In the inferior temporal rim, the area in which nerve bundle defects most commonly occur, blood flow is reduced by 28%. Patients with more advanced glaucomatous damage, as detected by visual field corrected pattern standard deviation and measurement of the cup-to-disc ratio, tend to have lower ONFlow5. These results suggest a decrease in optic nerve blood flow that is correlated with functional and morphologic measures of glaucomatous progression. However, from these results we cannot conclude whether this decrease in flow has a primary role in the etiology of glaucoma or whether it is the result of the loss of neural components caused by this disease.
PURPOSE: A recent report has suggested that nitrate therapy may delay the progression of glaucomatous damage. To investigate the mechanism that may mediate this effect, we sought to determine whether nitrate therapy is associated with retinal vasodilatation in patients with glaucoma. METHODS: Retinal venous and arterial diameters were determined from color fundus photographs of the optic nerve head obtained during a retrospective study designed to investigate any potential effects of chronic nitrate treatment on the progression of glaucomatous pathology. Fourteen eyes of 14 patients who were receiving chronic nitrate therapy for systemic diseases unrelated to glaucoma were randomly selected. Vascular measurements were compared with those of 15 eyes of 15 control patients with glaucoma who did not receive any nitrate therapy. RESULTS: In comparison with control patients, nitrate-treated patients showed significant average vasodilatation of 17% (P = .008) and 13% (P = .01) in the superior and inferior temporal retinal veins, respectively. A 5% increase in average retinal arterial diameter was also detected, but this was not statistically significant. CONCLUSION: Chronic nitrate treatment is associated with retinal venous dilatation in patients with glaucoma. Although not assessed in this study, it is possible that a protective effect of nitrates may be mediated by a vasoactive effect leading to improved perfusion of the retina and perhaps the optic nerve head, in a similar fashion to what has been observed in the circulation of the heart. Additional studies of the effect of nitrates on the ocular circulation are needed, however, to support this speculation.
PURPOSE: The effect of topical levobunolol HCl 0.5% on the retinal circulation was studied on 15 normal volunteers aged 21-54 years (32 +/- 10 years). METHODS: In a double-masked, randomised design, one eye of each subject received a drop of levobunolol HCl 0.5% (LEV) and the fellow eye received a drop of artificial tears (TEAR). Leucocyte velocity (VBFS) and density in the retinal macular microcirculation were measured by the blue-field simulation technique. Venous diameter (D), maximum erythrocyte velocity (Vmax) and volumetric blood flow rate (Q) were measured in a major temporal vein by laser Doppler velocimetry and monochromatic fundus photography. RESULTS: The following average changes from baseline were observed 2 hours after treatment: heart rate, -4.6 +/- 8.3% (p = 0.04); intraocular pressure, -31.7 +/- 10.6% (p = 0.0001); and perfusion pressure, 15.4 +/- 14.4% (p = 0.02) in LEV eyes; no statistically significant changes in IOP and perfusion pressure were seen in TEAR eyes. When each eye was compared with its own baseline, there were no significant changes in VBFS, density, D, Vmax and Q in LEV eyes. In TEAR eyes, there were no significant changes in VBFS, density, Vmax and Q, but a significant change in D (-1.8 +/- 2.6%; p = 0.02) was observed. A significant average percentage increase in Q of 10.9 +/- 19.2% (paired t-test between the change after LEV and the change after TEAR, p = 0.044) was seen in LEV eyes when compared with TEAR eyes. Twelve of the 15 subjects demonstrated a relative increase in Q in the LEV eyes in comparison with the TEAR eyes, while 3 subjects showed the opposite. CONCLUSION: A significant difference in the effect of levobunolol between the two eyes was detected, even though there was no statistically significant effect when each eye was compared with its baseline.
PURPOSE: To determine the effect of one week of topical treatment with levobunolol HCl 0.5% on the retinal circulation of normal subjects. METHODS: Fifteen healthy volunteers with no history of ocular disease were included in this study. In a double-masked, randomized, cross-over design, one eye of each subject was treated, for one week, with one drop of either levobunolol or placebo, administered twice daily. Following a washout period of at least three weeks, the same eye received the alternate treatment for one week. Before the beginning of therapy and then two hours after the last drop, vessel diameter (D), maximum erythrocyte velocity (Vmax), and volumetric blood flow rate (Q) were determined in one major retinal vein of the treated eye, using bidirectional laser Doppler velocimetry and monochromatic fundus photography. Statistical analysis was performed using two-tailed, paired Student's t-test, linear regression, and correlation analysis. RESULTS: The average percentage change from baseline in intraocular pressure was statistically significant following levobunolol (-15% +/- 13% (+/-1 SD), P < .001), but not following placebo (-3% +/- 11%, P > .05). No significant changes in average D, Vmax, or Q were observed after levobunolol treatment (-1% +/- 4%, 5% +/- 11%, 4% +/- 15%, respectively) or placebo treatment (-1% +/- 4%, -2% +/- 9%, -5% +/- 10%, respectively). The average difference between the changes in Q from baseline after levobunolol and placebo treatments (9% +/- 17%) achieved a significance level of P = 0.06. Furthermore, following levobunolol treatment, Q was 7% +/- 14% higher than following placebo treatment (P = 0.05). CONCLUSIONS: A comparison of the effects of placebo and levobunolol treatments suggests that levobunolol has a variable effect on the retinal circulation with a tendency to show an overall slight increase in flow.
PURPOSE: To study the effect of a single dose of topical dorzolamide hydrochloride 2%, a carbonic anhydrase inhibitor, on the retinal circulation of normal subjects. METHODS: Measurements of the effect of dorzolamide hydrochloride were performed in 20 normal subjects using bidirectional laser Doppler velocimetry and monochromatic fundus photography. In a double-masked randomized design, one eye received one drop of dorzolamide hydrochloride 2 % and the other eye one drop of placebo. Vessel diameter, maximum erythrocyte velocity and volumetric blood flow rate were measured in a main temporal vein of each eye before the drops, and then, 2 h later. RESULTS: Following treatment, intraocular pressure decreased by 12% in the dorzolamide-treated eye (p = 0.0004, paired Student's t-test) and by 4% in the placebo-treated eye, p = 0.04). No significant changes in venous diameter, maximum erythrocyte velocity, and volumetric blood flow rate were observed in the dorzolamide-treated eyes (0.6%, 2.6% and 1.4%, respectively) or the placebo-treated eyes (1%, 3.7% and 1.6%, respectively). CONCLUSIONS: A single drop of dorzolamide hydrochloride does not cause any significant change in any of the hemodynamic parameters measured. With the variability of our measurements, we have about 89% power to detect average 10% change in volumetric blood flow rate if significance testing is performed at p = 0.05 level.
PURPOSE: To investigate the retinal hemodynamic changes occurring in patients with retinitis pigmentosa (RP). METHODS: Bidirectional laser Doppler velocimetry and monochromatic fundus photography were used to determine retinal venous diameter (D), maximum erythrocyte velocity (Vmax), and volumetric blood flow (Q) in the major retinal veins of eight patients with RP and eight age-matched normal controls. The retinal vascular regulatory responses to hyperoxia, defined as the percent decreases in D (RD), Vmax (RVmax), and Q (RQ) at four to six minutes of breathing 100% oxygen, were determined in eight normal subjects and five RP patients. RESULTS: Average D, Vmax, and Q +/- S.D. in the largest retinal vein of each subject were 106 +/- 14 microns, 1.01 +/- 0.20 cm/sec, and 3.5 +/- 1.3 microliters/min, respectively, in RP patients, and 166 +/- 12 microns, 1.79 +/- 0.14 cm/sec, and 14.7 +/- 2.6 microliters/min, respectively, in normal subjects. This corresponded to significant decreases from normal of 36% in D, 44% in Vmax, and 76% in Q in RP patients (Wilcoxon's rank sum test, P < .001). Average total retinal volumetric blood flow rate was 8.2 +/- 2.9 microliters/min in RP patients and 37 +/- 4.9 microliters/min in normal subjects, corresponding to a significant decrease from normal of 78% (Wilcoxon's rank sum test, P < .001). In RP patients, the regulatory responses to hyperoxia (RD, RVmax, and RQ) were similar to those observed in normal subjects. RESULTS: Retinal blood flow is significantly decreased in patients with RP, probably as a result of vascular remodeling in response to reduced metabolic demand. The regulatory responses to hyperoxia are similar to those of normal subjects. Measurements of retinal blood flow may help assess the progression of the disease and the effects of treatment.
AIMS/BACKGROUND: The retinal circulation was investigated in a group of 19 patients with insulin dependent diabetes mellitus with less than 4 years of disease duration and no evidence of diabetic retinopathy. Results of these patients were compared with those of 16 age-matched normal controls. METHODS: Venous diameter (D) was measured from monochromatic fundus photographs. Maximum erythrocyte velocity (Vmax) was assessed by bidirectional laser Doppler velocimetry in the major retinal veins of one eye of each subject. Total volumetric blood flow rate (QT) was calculated by adding the flow rates of the major retinal veins. RESULTS: Average QT was 12% larger than normal in diabetic patients (one tailed, non-paired Student's t test, p < 0.05). A statistically significant correlation was observed between QT and disease duration (r = 0.35, p < 0.04). Patients with longer disease duration tended to have somewhat larger QT. The average retinal vascular regulatory responses to hyperoxia were not significantly different from normal in diabetic patients. In these patients, however, higher blood glucose levels were associated with decreased regulatory responses to hyperoxia. CONCLUSIONS: Patients with diabetes mellitus of relatively short duration have mildly increased QT, suggesting that increased blood flow may play an early role in the development of diabetic retinal microangiopathy.
AIMS: The effect of rebreathing into a bag (RB) on retinal macular blood velocity was evaluated in healthy volunteers. METHODS: Ten normal volunteers, whose ages ranged from 17 to 34 years, performed RB over 135 to 260 seconds (mean (SD) 193 (38) seconds) while retinal macular blood velocity was determined non-invasively using the blue field simulation technique. RESULTS: Leucocyte velocity significantly increased (p < 0.05) at 2 minutes and at the end of RB by 53% (42%) and 92% (65%), respectively (95% confidence interval of the mean (CIM)). All subjects observed an increase in the density of leucocytes. At the end of RB, mean systolic brachial arterial pressure and heart rate were significantly increased by 24% (11%) and 37% (15%) respectively (p < 0.01). At 2 minutes, end tidal oxygen concentration in the exhaled air was 47% (8%) (95% CIM) below and carbon dioxide was 41% (16%) above baseline (p < 0.001). The RB produces a large increase in macular leucocyte velocity, suggesting an increase in blood flow. CONCLUSION: Although RB has some systemic risk due to hypoxia and hypercapnia, RB for a short period of 1 or 2 minutes might be of help in the treatment of retinal arterial obstructive diseases in young patients without cardiovascular disorders if other treatments do not show any beneficial effects.
AIMS: The purpose of this study was to investigate the effect of instituting strict diabetic glycaemic control on the retinal macular microcirculation and to compare this effect with that observed in the main retinal veins. METHODS: In 28 insulin dependent diabetic patients with poor glycaemic control a regimen of strict diabetic control, consisting of four daily insulin injections was instituted and maintained for 6 months. Retinal haemodynamics were investigated in the macular microcirculation by the blue field simulation technique and in the major retinal veins by a combination of bidirectional laser Doppler velocimetry and monochromatic fundus photography. Progression of diabetic retinopathy was assessed from fundus photographs taken at baseline and at the end of the study. RESULTS: Institution of strict diabetic control resulted in a significant increase in leucocyte velocity in the macular circulation (p = 0.013). No significant difference in this increase was observed between eyes that showed progression (n = 8) and no progression (n = 20) of retinopathy during the study. Significant correlations were found between relative changes over time of blood flow measured in the main retinal veins and relative changes of leucocyte velocity determined in the macular microcirculation at 2 months (p = 0.008) and 6 months (p = 0.001) but not at 5 days (p = 0.49). In the eight eyes that showed progression of retinopathy, the product of leucocyte velocity and density at baseline was significantly higher than normal (p < 0.05). During the length of this study, this product was also significantly higher in the eight eyes that showed retinopathy progression than in the 20 eyes that did not show progression (p = 0.005). CONCLUSION: Our results suggest that increased flow in the macular microcirculation may be associated with progression of retinopathy, thus supporting the hypothesis that increased blood flow may play a role in the development of diabetic microangiopathy. Although there are correlations between the changes detected in the macular microcirculation and those measured in the main retinal vessels, there are also differences which need to be further investigated in order to better understand pathogenetic mechanisms.
We studied the ocular findings of two adult patients with the Eisenmenger's syndrome who had atrial septal defects that were diagnosed before the age of 10 years but not operated on and pulmonary hypertension. Both eyes of these patients showed microaneurysms, multiple small blot hemorrhages, or capillary dilation in the temporal peripheral fundus. Multiple microaneurysms and retinal collaterals were confirmed by fluorescein angiography. One of the patients developed bilateral rubeosis iridis with slow progression. These retinal lesions and the rubeosis iridis are probably related to chronic ocular ischemia caused by chronic systemic hypoxia.
The effects of strict diabetic control on retinal haemodynamics were studied to elucidate whether such effects are associated with retinopathy changes. In 28 patients with poorly controlled insulin dependent diabetes mellitus and non-proliferative retinopathy, retinal haemodynamics were investigated at baseline, 5 days, 2 months, and 6 months after the institution of strict diabetic control using the bidirectional laser Doppler velocimetry technique and monochromatic fundus photography. Changes in retinal blood flow measured in a major retinal vein (Q) on the fifth day of strict diabetic control correlated significantly with changes in retinopathy level observed at the end of the 6 months of this study (rank correlation 0.65, p < 0.01). On the fifth day of strict diabetic control, 16 out of 20 eyes that showed no progression (NP) of retinopathy at the end of the study had decreases in Q, whereas six out of eight eyes that showed progression (P) had increases in Q. The difference in these changes in Q between P and NP eyes was statistically significant (one way analysis of variance, p = 0.001). No significant changes in Q were detected at 2 months or 6 months. Following the institution of strict diabetic control, no significant changes in time were detected in the regulatory response to 100% oxygen breathing characterised as the percentage decrease in Q at 4-6 minutes of oxygen breathing (analysis of variance, p = 0.36). Changes in Q following institution of strict diabetic control are associated with progression of retinopathy. Measurements described in this study may help identify diabetic patients at risk of progression when their metabolic control is improved.
PURPOSE: To develop a noninvasive method for the investigation of choroidal blood flow (ChBF) and its regulation in the foveal region of the human ocular fundus. METHODS: Measurement of ChBF was based on the technique of laser Doppler flowmetry (LDF). Sixteen normal subjects (age range, 20 to 64 years), with normal eye examination results, were asked to fixate on a diode laser beam (wavelength = 811 nm, 60 microW at the cornea) delivered to the undilated eye through a fundus camera. Light scattered by red blood cells in the tissue volume sampled by the incident laser beam was detected at the fundus image plane of the camera by an optical fiber. The diameter of the beam at the fundus of the emmetropic eye was about 300 microns. Relative ChBF was measured in both eyes by analyzing the Doppler signal with commercial skin blood flowmeters. The average pulsatile component of ChBF, ChBFP, was determined over the cardiac cycle, and its value was compared to the average total ChBF, ChBFAV. Responses of ChBF to various physiological stimuli, such as increased blood O2 and CO2 concentrations, rapid increases in intraocular pressure, and valsalva maneuvers, were documented. RESULTS: Significant correlations were obtained between the ChBFAV values measured with both flowmeters (P < 0.001) and between the ChBFAV values measured in the right and left eye (P < 0.001). ChBFP represented less than 23% of ChBFAV. ChBFAV was not significantly affected by 5 minutes of breathing 100% oxygen. Raising end-tidal CO2 in one subject from 37 to 59 mm Hg increased ChBFAV by approximately 40%. Acute elevation of the intraocular pressure by suction cup or finger pressure on the globe reduced ChBFAV by as much as 90%. Valsalva maneuvers induced reproducible responses that were very different from those recorded from the skin microcirculation. CONCLUSIONS: Although LDF of the choroidal circulation is still at an early stage of development, this noninvasive method appears to provide continuous and sensitive measurements of relative choroidal blood flow in the foveal region of the human fundus. Near-infrared laser diodes enable measurements through undilated pupils. Examples of responses suggest new avenues in the investigation by LDF of the effect of various physiological stimuli, pharmacologic agents, and pathologic processes on the choroidal circulation in man.
PURPOSE: Structural changes in the retina are known to occur with aging. This study was performed to investigate whether aging also affects the retinal macular microcirculation. METHODS: Healthy volunteers with ages ranging from 20 to 78 years (mean +/- SD, 49 +/- 19 years) were included in this study. The retinal macular microcirculation was assessed with the blue field simulation technique, based on the blue field entoptic phenomenon. Subjects were asked to match the velocity and density of computer-simulated particles displayed on a screen with those of their entoptically observed leukocytes. Ten matching trials were performed, and an average leukocyte velocity and density were calculated. RESULTS: Significant negative linear correlations were observed between velocity and age (P = 0.0001) and density and age (P = 0.009). Older subjects (50 to 78 years of age) had a significantly slower velocity (0.61 +/- 0.21 mm/s) and smaller density (90 +/- 43 particles per field of view) than younger subjects (0.92 +/- 0.12 mm/s and 135 +/- 65 particles, respectively; unpaired Student's t-test, P = 0.001 and P = 0.01, respectively). CONCLUSIONS: These results suggest that, in normal subjects, retinal macular blood flow decreases with age. The 20% decrease in average velocity with age is very similar to the age-related decrease in number of cells observed in the human foveal ganglion cell layer.
PURPOSE: Carbogen, a gas mixture of 95% O2 and 5% CO2, is given to patients with retinal artery obstruction in an attempt to improve retinal oxygenation. The purpose of this study was to compare the effects of carbogen and 100% O2 breathing on retinal blood flow. METHODS: On two separate occasions, 12 normal, healthy volunteers breathed air and then either 100% O2 or carbogen while laser Doppler velocimetry measurements and monochromatic fundus photographs were taken. Retinal vessel diameter, maximum velocity of red blood cells, and volumetric blood flow rate were determined in a main temporal vein. RESULTS: Both 100% O2 and carbogen caused significant average reductions in vessel diameter (14.1% and 10.6%, respectively), maximum red blood cell velocity (42.1% and 27.3%, respectively), and blood flow (56.4% and 42.2%, respectively). The average vasoconstriction of the large retinal veins caused by carbogen was not significantly smaller than that caused by 100% O2. The average reductions in maximum red blood cell velocity and blood flow caused by carbogen were significantly smaller than those caused by 100% O2 (P < .001 and P < .01, respectively). CONCLUSIONS: In normal subjects, inhalation of carbogen leads to less reduction in blood flow than inhalation of 100% O2, presumably by reducing the vasoconstriction of small arterioles induced by elevated oxygen levels.
PURPOSE: This study investigated retinal hemodynamic changes associated with different pathologic features observed on fundus color and fluorescein angiography in patients with proliferative diabetic retinopathy. METHODS: Retinal circulatory characteristics were investigated in 25 eyes of 23 diabetic patients with proliferative retinopathy using a combination of bidirectional laser Doppler velocimetry and monochromatic fundus photography. RESULTS: Eyes with severe capillary nonperfusion had 32% less average volumetric blood flow rate (Q) than eyes with less severe nonperfusion (P = 0.0005). In addition, eyes with severe vessel staining with fluorescein had 20% less average Q than eyes without staining (P = 0.0508). Eyes with severe fluorescein leakage in the macula had a 17% larger total venous cross-section than eyes with milder leakage (P = 0.027). Eyes with clinically significant macular edema had 11% larger average venous diameter than eyes without this feature (P = 0.0085). CONCLUSIONS: Severe capillary nonperfusion and vessel staining with fluorescein are associated with decreased retinal blood flow rates. Vasodilatation may be an important factor for increased vascular permeability and macular edema in proliferative diabetic retinopathy.
Acetazolamide has been shown to be beneficial in the treatment of macular edema. To investigate whether this effect is associated with changes in the retinal circulation, the acute effect of oral acetazolamide on macular blood flow was studied in 20 healthy volunteers. The blue-field simulation technique, a noninvasive method enabling the quantitation of the number (N) and mean velocity (Vm) of leukocytes flowing in the subject's own macular capillaries was used in this study. On two different occasions, separated by 3 or more days, 20 subjects adjusted Vm and N of computer-simulated leukocytes moving on a video screen to match those of their own entoptically perceived leukocytes before and 3 hr after a double-blind, randomized administration of 500 mg acetazolamide or placebo capsules. Ten trials were done, and the velocities were averaged. After acetazolamide ingestion, there was a nonsignificant average change from baseline in Vm (2.5 +/- 23% [+/- one standard deviation]; P greater than 0.1, by paired student t-test) and N (6.9 +/- 25%, P greater than 0.1). After placebo ingestion, the average changes from baseline in Vm and N also were not statistically significant (-1 +/- 18% and 14.9 +/- 30.3%, respectively). Furthermore, when compared with the changes measured after placebo intake, acetazolamide ingestion was associated with a nonsignificant 4.3 +/- 28.7% change in Vm (P greater than 0.1) and a -8 +/- 30.9% change in N (P greater than 0.1). With 20 subjects tested, the calculated average minimum change in leukocyte velocity that could have been detected with this technique (P less than 0.05, by paired student t-test) is about 9%.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of topical carteolol 1%, a beta-adrenergic blocker with intrinsic sympathomimetic activity, on the retinal circulation was investigated in 15 normal subjects using laser Doppler velocimetry and monochromatic fundus photography. In a double-masked randomized design, one eye received one drop of carteolol 1% and the fellow eye one drop of placebo. Vessel diameter, maximum erythrocyte velocity, and volumetric blood flow rate were determined in a major temporal vein of each eye just before instillation of the drops and then 120 min later. No significant changes in heart rate or mean brachial artery blood pressure were detected after treatment. Intraocular pressure decreased by 28% in the carteolol-treated eye (P less than 0.0001) and by 15% in the placebo-treated eye (P less than 0.001). No significant changes in vessel diameter, maximum erythrocyte velocity, and volumetric blood flow rate were observed in the carteolol-treated eyes (0.3%, 4.3%, and 3.6%, respectively) or the placebo-treated eyes (0.5%, 5.8%, and 6.7%, respectively).