Douglas G. Goger

Laser Doppler Technique for Absolute Measurement of Blood Speed in Retinal Vessels

We describe an electrooptical laser Doppler system and technique of data analysis that provides absolute measurements of the speed of red blood cells flowing at discrete, selectable sites in the retinal vasculature. We present in vitro test measurements of the instrumentation as well as an example of an in vivo measurement from a patient with retinal vascular disease. We also present experimental data leading to the derivation of the relationship between the blood speeds measured in retinal arteries during the minimum diastolic and maximum systolic phases of the cardiac cycle and the time-averaged blood speed. Mean blood flow rate is calculated using the time-averaged speed and the cross-sectional area of the vessel at the measurement site. We discuss the criteria for selection of the measurement sites and assess the reproducibility of the measurements. We conclude that measurements on retinal arteries are less susceptible to experimental artifacts and provide more information than do measurements on retinal veins. The system is currently being used clinically in studies of retinal circulatory alterations in patients with diabetic retinopathy, arterial occlusive disease, retinal detachment, and carotid artery disease.

Retinal Circulatory Changes after Scleral Buckling Procedures

The noninvasive laser Doppler technique was used to study retinal circulatory characteristics in five patients who underwent uncomplicated scleral buckling procedures. In each patient, the systolic/diastolic variation of the red blood cell speed in the retinal arteries (flow pulsatility ratio) was lower in the eye that had received an intrascleral implant and an encircling band than in the fellow eye. In one patient, an increase in flow pulsatility ratio accompanied an increase in retinal blood flow after removal of the scleral buckling elements. In another patient, the flow pulsatility ratio in the eye that had received a solid implant and an encircling band was less than the ratio in the fellow eye that had received an absorbable implant alone. Our results indicated that reduced retinal blood flow may be common after scleral buckling procedures, and may be a significant factor in otherwise inexplicable postoperative complications.

Bimodal spatial distribution of macular pigment: evidence of a gender relationship

The spatial distribution of the optical density of the human macular pigment measured by two-wavelength autofluorescence imaging exhibits in over half of the subjects an annulus of higher density superimposed on a central exponential-like distribution. This annulus is located at about 0.7 degrees from the fovea. Women have broader distributions than men, and they are more likely to exhibit this bimodal distribution. Maxwells spot reported by subjects matches the measured distribution of their pigment. Evidence that the shape of the foveal depression may be gender related leads us to hypothesize that differences in macular pigment distribution are related to anatomical differences in the shape of the foveal depression.

Effect of Timolol on Human Retinal, Choroidal and Optic Nerve Head Circulation

In a double-masked, randomized, placebo-controlled study, we evaluated the effect of topical timolol maleate 0.5% on the retinal, choroidal, and optic nerve head circulation in 5 healthy volunteer subjects. Changes in the pulsatile component of choroidal blood flow (PCBF) were determined from measurements of the ocular pulse wave. Changes in the retinal arterial blood flow rate (RBF) and optic nerve head capillary blood speed (CBS) were determined by laser Doppler velocimetry and monochromatic photography. In timolol-treated eyes, PCBF decreased by 32 +/- 12% (p = 0.0007). Changes in RBF and CBS were not statistically significant. In the contralateral placebo-treated eyes, PCBF decreased by 15 +/- 8% (p = 0.006) and RBF increased by 18 +/- 10% (p = 0.002). The change in CBS was not statistically significant.

Laser Doppler Measurements of the Effect of Panretinal Photocoagulation on Retinal Blood Flow

The laser Doppler technique was used to measure the pulsatile characteristics of the retinal arterial blood flow in diabetic patients with severe retinopathy immediately before argon laser panretinal photocoagulation (PRP) and again one to two months after PRP. In each measurement the relative variation of the maximum red blood cell velocity, Vmax, in a major branch retinal artery was determined throughout the cardiac cycle. Flow pulsatility was defined as the ratio of Vmax at maximum systole to Vmax at minimum diastole. Following PRP, each eye showed a decrease in flow pulsatility as well as a decrease in retinal arterial and venous diameters. The measurements are consistent with an autoregulatory response of the retinal circulation to increased inner retinal oxygen concentration following PRP. Laser Doppler measurements may be a useful means of assessing the effectiveness of a particular PRP treatment.

Retinal Circulatory Changes Related to Retinopathy Progression in Insulin-dependent Diabetes Mellitus

To quantify the vascular deterioration of the diabetic retina, retinal circulatory changes in 45 insulin-dependent diabetic patients, and in 17 normal controls, were measured and divided into four groups according to severity of retinopathy. The noninvasive laser Doppler technique was used to measure the systolic/diastolic variation of red blood cell velocity (V) at sites along temporal retinal arteries. Flow pulsatility [V (systole)/V (diastole)] was 18% lower (P less than 0.00001) in the mild-retinopathy group than in normal controls, but 35% higher (P less than 0.001) in the severe-retinopathy group than in the mild-retinopathy group. Repeated measurements in three eyes during the progression from mild or moderate to severe retinopathy showed progressive increases in both flow pulsatility and mean retinal blood flow. Altered flow pulsatility appears to be a sensitive indicator of vascular alterations during the progression of diabetic retinopathy.

Optic Nerve Head Circulation After Topical Calcium Channel Blocker

PURPOSE Our purpose was to investigate the effects of the calcium channel blocker verapamil on intraocular pressure and blood circulation in the human optic nerve head. METHODS The effects of three different concentrations of topical verapamil (0.063%, 0.125%, and 0.25%) on intraocular pressure and optic nerve head capillary blood speed were measured in 12 healthy normal subjects. In a randomized, double-masked design, each subject received one drop of either verapamil or placebo in one eye and the opposite treatment in the fellow eye. Anterior optic nerve circulation was assessed at baseline and 90 min after instillation of the drops using the laser Doppler technique. RESULTS The intraocular pressure was significantly reduced compared with baseline in both verapamil- and placebo-treated eyes at each concentration. The reductions of intraocular pressure were greater in verapamil-treated eyes (12-17%) than in placebo-treated eyes (9-12%). No systemic effect on heart rate or blood pressure was detected after administration of topical verapamil. The capillary blood speed in the optic nerve head was increased in both verapamil- and placebo-treated eyes at each concentration, although the only statistically significant increases were with the 0.25% concentration. The mean +/- SEM increase compared with baseline at the 0.25% concentration was 10.4 +/- 3.6% in verapamil-treated eyes (p = 0.017), and 11.6 +/- 4.4% in placebo-treated eyes (p = 0.026). CONCLUSIONS These results indicate that topical administration of verapamil lowers the intraocular pressure and increases the capillary blood speed in the optic nerve head in normal subjects. Changes measured in verapamil-treated eyes were also observed in placebo-treated eyes, indicating a crossover effect.

Retinal Hemodynamics in Middle-Aged Normal Subjects

The laser Doppler technique and monochromatic photography were used to measure the total retinal blood flow, temporal/nasal differences in blood flow and the relationship between blood flow and vessel diameter in 5 healthy subjects, aged 54-58 years. Systemic blood pressure (BP) and intraocular pressure were also measured, and the retinal perfusion pressure was calculated. The measurements were compared to those previously obtained from a younger group of 7 healthy subjects, aged 25-38 years. Total retinal blood flow was 73 +/- 13 microliters/min in the middle-aged subjects and was not significantly different from the value measured in young subjects (80 +/- 12 microliters/min). Retinal perfusion pressure was significantly higher in the older subjects, primarily due to elevated systemic BP. The similarity in total flow between the two groups, even though the retinal perfusion pressures were higher in the older group, is an indication of an increased vascular resistance to flow. The increase may be an aging phenomenon or an indication of a well-functioning autoregulatory capacity in the retinal vasculature of the older subjects.

Diversity of response of optic nerve head circulation to timolol maleate in gel-forming solution.

PURPOSE This randomized, double-masked, placebo-controlled, two-period crossover study was conducted to investigate the effects of 0.5% timolol maleate in gel-forming solution on intraocular pressure (IOP) and blood circulation in the optic nerve head in patients with untreated ocular hypertension. METHODS The effects of 0.5% timolol in gel-forming solution on IOP and optic nerve head capillary blood speed were studied in 12 patients with untreated ocular hypertension. Optic nerve capillary blood speed was measured using the laser Doppler technique before and at the end of each treatment period. RESULTS In each patient, IOP decreased after treatment with timolol (mean decrease 16.8% versus placebo). Systemic blood pressure and pulse rate did not differ significantly after treatment with topical timolol from values after placebo. The mean change from baseline in Doppler broadening was 10.6% greater after treatment with timolol than after placebo. There was no significant change in mean Doppler broadening from baseline after treatment with either timolol or placebo. However, optic nerve head capillary blood speed increased in six patients, and was within the range of placebo response in six patients after treatment with timolol. Spearman correlation analysis of the baseline with Doppler broadening measurements after treatment showed a correlation for placebo but not for timolol. The percent change in Doppler broadening after timolol treatment was correlated with iris color. CONCLUSION These results indicate that administration of timolol for 4 weeks reduces IOP in patients with ocular hypertension and generally does not change the blood circulation in the optic nerve head. Individual patients, however, showed variable changes in optic nerve head circulation after topical administration of timolol. Although the sample size was small, these changes in optic nerve head circulation were correlated with iris color.