Heidelberg Retina Flowmeter Research Articles

Macular Capillary Blood Flow in Patients with Diffuse Diabetic Macular Edema without Vitreomacular Traction

Background: To evaluate macular microcirculation in patients with unilateral diffuse diabetic macular edema (DME) in order to determine whether the alteration in macular microcirculation is associated with development of diffuse DME without vitreomacular traction. Methods: According to the presence of epiretinal membrane (ERM), 27 patients having unilateral diffuse DME were divided into DME without ERM (non-ERM-DME group, n = 12) and with ERM (ERM-DME group, n = 15). Twelve patients with macular edema associated with unilateral branch vein obstruction (BVO) and 10 nondiabetic healthy subjects were enrolled as controls. Macular blood flow measured by Heidelberg retinal flowmeter was compared between the edematous eye and the nonedematous fellow eye of each patient and between groups. The macular thickness was evaluated with optical coherence tomography. Results: The mean macular blood flow was significantly higher than that of the contralateral eyes in edematous eyes of non-ERM-DME group (798.8 vs. 379.8 AU, p < 0.001). By contrast, in the ERM-DME group, the mean macular blood flow of DME eyes was similar to that of fellow eyes (575.9 vs. 596.4 AU, p = 0.538). The macular capillary blood flow in patients with BVO was not significantly different compared with nondiabetic controls (p = 0.967). Conclusions: The results suggest that the alteration of macular microcirculation may play a role in the pathogenesis of diffuse DME without vitreomacular traction.

Inability of a Confocal Scanning Laser Doppler Flowmeter to Measure Choroidal Blood Flow in the Pig Eye

The aim of the study was to determine whether the Heidelberg Retinal Flowmeter (HRF), a confocal scanning laser Doppler flowmeter, can measure choroidal blood flow in pig eyes.An HRF was used to obtain flow maps from in vitro pig eyes under a range of perfusion flow rates (0 – 500 µL/min) under conditions in which only the choroid was perfused. In some cases choroidal blood flow was also measured simultaneously using a conventional fiberoptic based Laser Doppler Perfusion Monitor (LDPM) which used the same laser wavelength (780 nm). The relationship between perfusion flow, HRF measured flow and LDPM measured flow was determined. HRF flow maps were also obtained in vivo as a function of focal plane setting through the retina and choroid.Across the range of perfusion flow rates through the isolated eyes there was a poor correlation with HRF measured choroidal flow and perfusion flow. In contrast, there was a strong linear relationship between perfusion flow and LDPM measured blood flow. Both in vitro and in vivo, no choroidal vessels could be visualised in the HRF flow maps, even when the focal plane was in the choroid.The HRF is unable to measure choroidal blood flow in pig eyes. This is not due to an inability of the 780 nm laser to penetrate into the choroid or due to red blood cell velocities in the choroid being higher than the measurement range of the instrument.

Retinal arteriolar and capillary vascular reactivity in response to isoxic hypercapnia

The aim of the study was to compare the magnitude of vascular reactivity of the retinal arterioles in terms of percentage change to that of the retinal capillaries using a novel, standardized methodology to provoke isoxic hypercapnia. Ten healthy subjects (mean age 25 years, range 21–31) were recruited. Subjects attended a single visit comprising two study sessions separated by 30 min. Subjects were fitted with a sequential re-breathing circuit connected to a computer-controlled gas blender. Each session consisted of breathing at rest for 10 min (baseline), increase of P ETCO 2 (maximum partial pressure of CO 2 during expiration) by 15% above baseline whilst maintaining isoxia for 20 min, and returning to baseline conditions for 10 min. Retinal hemodynamic measurements were performed using the Canon Laser Blood Flowmeter and the Heidelberg Retina Flowmeter in random order across sessions. Retinal arteriolar diameter, blood velocity and flow increased by 3.3%, 16.9% and 24.9% ( p < 0.001), respectively, during isoxic hypercapnia. There was also an increase of capillary blood flow of 34.8%, 21.6%, 24.9% ( p ≤ 0.006) at the optic nerve head neuroretinal rim, nasal macula and fovea, respectively. The coefficient of repeatability (COR) was 5% of the average P ETCO 2 both at baseline and during isoxic hypercapnia and was 10% and 7% of the average P ETO 2 (minimum partial pressure of oxygen at end exhalation), respectively. The overall magnitude of retinal capillary vascular reactivity was equivalent to the arteriolar vascular reactivity with respect to percentage change of flow. The magnitude of isoxic hypercapnia was repeatable.

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.

Epidemiology and follow‐up of pigmentary glaucoma in Calabria

Abstract Purpose: To evaluate the incidence of pigmentary glaucoma (POAG) in Calabria. Methods: Subjects were patients newly diagnosed with pigmentary glaucoma during 2006 who came to our Centre of Glaucoma. We performed a full ofthalmological examination: Best Corrected Visual Acuity, slit lamp biomicroscopy, pachimetry, gonioscopy, measurement of intraocular pressure (IOP) with applanation tonometry,tonometric IOP curve, fundus oculi, Heidelberg Retina Tomograph, Heidelberg Retina Flowmeter, Nerve fiber analyzer, visual field, Optical Coherence Tomography, Ocular Blood Flow System, monitorated ambulatory pressure, sovraortic vessels doppler and transcranic doppler. Criteria for POAG were: pigment dispersion (mild, intermediate, severe), IOP greater than 21 mmHg, optic nerve damage and visual field loss. Results: A total of 87/150 (58%) patients presenting open angle glaucoma have been examined at the “Glaucoma Clinic Center” during the study (three times for year). 41/87 ( 47.12%) of them had POAG (with open angle grade 2‐4), 22 females and 19 males (mean age 48+/‐12 years old, M+F). The male‐female ratio was 1:1,1. Conclusions: The incidence of POAG in Calabria was 1:500 (0,2%).Owing the high frequency of POAG in Calabrian glaucoma patients we believe that performing at least a one time year follow‐up in these patients is helpful in preventing ocular complications.

Changed retinal capillary flow in patients with disc haemorrhages

Abstract Purpose: Vascular pathogenesis in glaucoma has been recognized and optic disc haemorrhages (DH) may pre‐cede nerve fiber damage in glaucoma. The change in peripapillary retinal capillary flow after resorbtion of DH was investigated. Methods: Included were 25 eyes of 25 patients with DH. 17 eyes had glaucoma. Peripapillary retinal capillary flow was measured with the Heidelberg Retina Flowmeter in arbitrary units (AU). The first measure‐ment was made right after diagnosis of DH and the second six months later. Automatic full field perfu‐sion image analyser was used for analysis. Mean flow (MF), peak systolic flow (SF), and minimum dia‐stolic flow (DF) were measured, and pulsation index (PI) calculated. Flow values are reported from the whole temporal peripapillary retina (Area 1), the same horizontal level as the DH (Area 2), and from the area specifically around the DH (Area 3). Results: A significant increase in MF after resorbtion of DH was detected in Area 1 (median 263 AU, range 188 – 561 AU, vs. 328 AU, 199 – 462 AU; P = 0.008), and Area 2 (255 AU, 166 – 386 AU, vs. 330 AU, 198 – 646 AU; P=0.04). The increase in MF in Area 3 was of borderline significance (342 AU, 230 – 513 AU, vs. 402 AU, 200 – 629 AU; P = 0.10), as was the increase in SF in Area 2 (334 AU, 187 – 486 AU, vs. 400 AU, 227 – 690 AU; P = 0.07). No significant changes in DF or PI were found. Conclusions: Increase in retinal capillary flow after resorbtion of DH suggests a generalized decrease in retinal flow at the time DH is detected, or a compensatory increase after ischemia.

Assessment of Variation in Bulbar Conjunctival Redness, Temperature, and Blood Flow

To assess the diurnal variation in bulbar conjunctival redness, conjunctival temperature, and conjunctival blood flow. Bulbar redness was quantified by CIE u' chromaticity using a SpectraScan PR650 spectrophotometer. Conjunctival temperature was measured using a Tasco-Thi 500 infrared thermometer. Measurements of conjunctival blood flow were obtained using a modified Heidelberg Retinal Flowmeter (HRF). Measurements on 10 subjects were made on a periodic basis over the day and on waking. For each factor measured a cyclical pattern was observed, with highest values on waking, a reduction in values towards mid-day, and then a gradual increase over the remainder of the day. There was a significant effect of time for redness, temperature, and conjunctival blood flow (p < 0.001 for all three variables), with no significant difference in the cyclical pattern between eyes being observed (p = NS). Diurnal bulbar redness, temperature, and conjunctival blood flow variation may be objectively quantified and all three are lowest during the middle of the day and maximal at the start of the day. This information should be considered when undertaking studies in which redness, temperature, and ocular surface blood flow are important outcome variables and time of day is a potential confounding factor.

Retinal Blood Flow Autoregulation after Dynamic Exercise in Healthy Young Subjects

Purpose: To evaluate the retinal blood flow before and after the increase in systemic blood pressure to assess the autoregulation in healthy young subjects. Methods: Twenty eyes of 20 healthy volunteers were examined. The retinal blood flow was assessed by a Heidelberg retina flowmeter (HRF), while the systemic pressure was assessed by a portable electronic sphygmomanometer. Furthermore intraocular pressure (IOP) was always measured by a Goldmann tonometer immediately after HRF assessments. All measurements of physiological and flow parameters were performed with the subjects seated at rest and then immediately after stair climbing. Results: The IOP decreased significantly after dynamic exercise, while the heart rate and the systemic artery pressure increased significantly. At the baseline, the mean retinal blood flow was 276.8 ± 80.7 arbitrary units (AU) in the superotemporal area, 243.4 ± 63.68 AU in the superonasal area, 258.2 ± 67.37 AU in the inferotemporal area and 243.9 ± 72.24 AU in the inferonasal area. After dynamic exercise the mean retinal blood flow was 249.8 ± 86.78 AU in the superotemporal area, 248.7 ± 63.87 AU in the superonasal area, 245.4 ± 83.85 AU in the inferotemporal area and 228.8 ± 62.53 AU in the inferonasal area. No significant change in retinal blood flow was found. Conclusion: Our data support the hypothesis that in normal subjects autoregulation is sufficient to compensate the increase in blood pressure and maintain a stable retinal blood flow after exercise.

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.

Increased Retinal Blood Flow in Patients with Active Graves' Ophthalmopathy

Purpose: To investigate retinal blood flow by Heidelberg retina flowmeter in patients with active Graves' ophthalmopathy. Materials and Methods: Thirty patients with active Graves' ophthalmopathy in euthyroid state and thirty normal controls were enrolled in this study. All subjects underwent heart rate, systolic and diastolic blood pressure detection, complete ophthalmological examination, Hertel's exophthalmometry, and retinal blood flow analysis by Heidelberg retina flowmeter. Patients additionally underwent automated threshold perimetry and extraocular muscle thickness measurement by A-scan ecography. Results: A significant statistical difference was found in exophthalmometry (P < 0.001), intraocular pressure (P < 0.001) and retinal blood flow (P < 0.05) between patients and controls. In patients, muscle enlargement was significantly correlated with retinal blood flow (r = 0.49, P = 0.005) and proptosis (r = 0.37, P = 0.04). A significant positive correlation (r = 0.52, P = 0.002) was also found between intraocular pressure and proptosis. Conclusions: Active Graves' ophthalmopathy patients present an increased retinal blood flow.

Microcirculation in Eyes After Rhegmatogenous Retinal Detachment Surgery

Purpose: To investigate the tissue blood flow in the neuroretinal rim of the optic disk and macula after rhegmatogenous retinal detachment (RRD) surgery. Methods: Tissue blood flow in the neuroretinal rim of the optic disk and macula was measured with the Heidelberg retina flowmeter in 53 eyes of 53 patients who had undergone successful surgery for unilateral RRD. Patients were divided into three groups; those who had the RRD treated by conventional encircling scleral buckling (group E), by local buckling (group L), and by primary vitrectomy (group V). Blood flow measurements were made more than 6 months after surgery in a 10° × 2.5° area of the superior and inferior margins of the neuroretinal disk rim and of the superior and inferior macula area. The mean blood flow (MBF) and the ratio of the MBF in the affected eye to the healthy fellow eye (a/f ratio) were compared among the three groups. The influence of several clinical factors on the MBF was also investigated. Results: The MBF rate and mean a/f ratios of the MBF of the three groups were not significantly different. Multiple regression analysis revealed that the averaged MBF both at superior and inferior disk rims was significantly correlated with only the gas tamponade procedure. Conclusions: The ocular microcirculation is normal 6 months after scleral buckling or vitrectomy for RRD. However, the use of gas tamponade might have a subclinical adverse effect on the circulation in the neuroretinal disk rim.

First-line therapy with latanoprost 0.005% results in improved ocular circulation in newly diagnosed primary open-angle glaucoma patients: a prospective, 6-month, open-label study

To evaluate the effect of latanoprost 0.005% on the optic nerve head (ONH) and retinal circulation of newly diagnosed and previously untreated primary open-angle glaucoma (POAG) patients. Twenty-two newly diagnosed and previously untreated POAG patients (mean age+/-SD: 68.38+/-11.92 years) were included in this longitudinal open-label study. Patients were treated with latanoprost 0.005% once a day. Intraocular pressure (IOP), systemic blood pressure (BP), mean ocular perfusion pressure (MOPP), and ocular perfusion parameters 'volume', 'velocity', and 'flow' measured at the optic nerve head (ONH) and retina by means of Heidelberg Retina Flowmeter system were evaluated during a 6-month follow-up period. Treatment with latanoprost 0.005% resulted in a significant decrease in IOP (P<0.0001) and increase in MOPP (P<0.0001). After correcting for changes in MOPP, the blood velocity measured at the ONH level was significantly higher after 6 months of treatment than at baseline (P=0.0310). In addition, blood volume and flow measured at the peripapillary retina level improved after 3 and 6 months of treatment (P=0.0170; P=0.0260, and P=0.0170; P=0.0240 respectively). Previously untreated POAG patients exhibit reduced IOP, increased MOPP and improved ocular perfusion at the ONH and retina levels when treated with Latanoprost 0.005%. These effects could be beneficial for glaucoma patients suffering from ocular vascular dysregulation.

Relaxation of Encircling Buckle Improved Choroidal Blood Flow in a Patient with Visual Field Defect Following Encircling Procedure

We report a patient with a visual field defect after retinal reattachment by the encircling procedure for rhegmatogenous retinal detachment. We confirmed improved ocular blood flow after relaxation of the buckle. A 24-year-old woman with a visual field defect appearing after an encircling procedure for rhegmatogenous retinal detachment. Before and after relaxing the encircling buckle, we measured tissue blood flow in the fundus of each eye of the patient using a Heidelberg retina flow meter. Preoperative measurements showed a reduction of blood flow at the disc rim in the diseased fundus, while retinal blood flow was not reduced (P = 0.026, disc rim area versus retinal area, one-factor analysis of variance, ANOVA). Indocyanine green angiography showed extensive peripheral filling delay. Electroretinography showed low a-wave and b-wave amplitudes, but normal oscillatory potential. The base value of the electro-oculogram was severely reduced in the right eye. The blood flow values after surgery indicated a significant improvement of blood flow (P = 0.01, one-factor ANOVA). No further progression in the visual field defect was observed, and visual acuity of the right eye improved from 0.8 to more than 1.0. These results suggest that the choroidal circulation disturbance, which was found after the encircling procedure, had a plausible role in the development of the visual field defect.

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.

Microcirculation at optic disc rim is correlated with visual field defects in cases of anterior ischaemic optic neuropathy

We report two cases of anterior ischaemic optic neuropathy in whom tissue blood flow at the disc rim was correlated with the visual field defect. Tissue blood flow of each eye was evaluated with Heidelberg retina flowmeter. Both cases experienced acute visual loss and an altitudinal hemianopsia associated with optic disc oedema in the affected eye. In each case, the tissue blood flow at the affected (upper or lower half) disc rim corresponding to visual field deficit was reduced compared with that at the opposite-sided half disc rim in the affected eye and with the corresponding area in the fellow eye. The reduction of blood flow in the affected half disc rim associated with the visual field defect demonstrated that retina flowmetry can detect differences in tissue blood flow between superior and inferior sectional disc rim areas as well as between eyes non-invasively.

Confocal Scanning Laser Doppler Flowmetry in the Rat Retina

To investigate the origin of signals from scanning laser Doppler flowmetry (SLDF) and the influence of axial scan depth on the measurement of blood flow in the rat retina. We performed SLDF in 5 adult Sprague-Dawley rats using a specially modified Heidelberg retina flowmeter. Axial scans were obtained from +2 diopters (D) to -3 D (in steps of 0.25 D) or from +1 D to -2 D (in steps of 0.125 D) relative to the retinal surface. Fluorescein isothiocyanate-dextran angiograms were obtained in whole-mounted retinas to visualize the angioarchitecture and identify measurement locations in the SLDF flow maps. Axial SLDF flow profiles were obtained in an artery, vein, arteriole, venule, and capillary bed using the mean blood flow values in 2 x 2-, 4 x 4-, and 10 x 10-pixel measurement windows. The SLDF images showed good correspondence with the angiograms and resolution to third-order arterioles and venules; however, neither the superficial nor deep capillary circulations were visualized. Flow was imaged from large choroidal vessels. Measured flow from capillaries was independent of depth and indistinguishable from background levels. The technique of SLDF images blood flow in larger retinal vessels but not in capillaries. Clinical Relevance Scanning laser Doppler flowmetry may not reliably measure capillary blood flow.

Decreased blood flow at neuroretinal rim of optic nerve head corresponds with visual field deficit in eyes with normal tension glaucoma

To determine the relationship between the blood flow parameters of the optic disc rim and the glaucomatous visual field changes. Observational cross-sectional study. Tissue blood flow in the neuroretinal rim within the optic disc was determined with the Heidelberg retina flowmeter(HRF) in 54 eyes of 54 patients with normal tension glaucoma (NTG). Patients were selected whose visual field defects were confined to either the superior or inferior hemifield. Blood flow measurements were made in a 10 degrees x 2.5 degrees area of the superior and inferior neuroretinal rim within the optic disc. The mean blood flow (MBF) was calculated by the automatic full-field perfusion image analyzer program, and the ratio of the MBF in the superior to the inferior rim areas (the S/I ratio) was calculated from the same HRF image in order to minimize the variation of measurement condition. Inferior rim blood flow is less than superior rim blood flow in patients with superior hemifield defect, and superior rim blood flow is reduced compared to inferior in patients with inferior hemifield defect. The mean S/I ratios of the MBF in the patients with superior hemifield defect (1.46, n=37) was significantly higher than that in the patients with inferior hemifield defect (0.79, n=17; P<0.0001, Mann-Whitney U-test). The blood flow in the neuroretinal rim was found to correspond to the regional visual field defect in eyes with NTG. Reductions in flow were associated with reductions in function.

Observer interpretation variability of peripapillary flow using the Heidelberg Retina Flowmeter

To evaluate the intraobserver and interobserver reproducibility of the automatic full field perfusion image analysis (AFFPIA) program on Heidelberg Retina Flowmeter (HRF) derived perfusion images in a multicentre study group. A total of 10 subjects were consecutively recruited in the study. One eye was randomly selected for each patient. Blood flow was assessed by HRF and flow measurements were analyzed by using the AFFPIA program. AFFPIA calculates the Doppler frequency shift and the haemodynamic variables: flow for each pixel. Intraobserver and interobserver reproducibility was calculated for AFFPIA program. The retinal blood flow was calculated in the superior and inferior section, furthermore, each section was divided into three parts: the temporal area, the nasal, and the rim area, as for software, but only the temporal and nasal areas were considered in this study. The blood flow and the area considered were evaluated for each part. When the intraobserver and intraimage reproducibility was studied, the coefficient of variation ranged from 0.4 to 1.9%. When the interobserver and intraimage reproducibility was studied, the retinal blood flow coefficient of variation ranged from 0.52 to 3.30% for the supero-temporal area, from 0.13 to 2.67% for the inferotemporal area, from 0.15 to 2.75% for the supero-nasal area, and from 0.04 to 5.65% for the infero-nasal area. Our results with AFFPIA showed an interobserver coefficient of variation of retinal blood flow measurements always less than 6% in both temporal and nasal areas. No significant difference was found among the four observers for the flow measurements.

Confocal laser Doppler flowmeter measurements in a controlled flow environment in an isolated perfused eye

The aim of this study was to improve our ability to interpret and validate Heidelberg Retina Flowmeter (HRF) flow images by recording flow measurements from specific regions of the retinal vasculature by taking advantage of the ability to precisely regulate perfusion flow in an isolated eye preparation. The retinal vasculature in 16 isolated perfused pig eyes was perfused with a 50%/50% Krebs/RBC solution at known flow rates ranging from 0 to 300 μl min −1. At each flow rate, HRF images were obtained at a location approximately two disc diameters from the disc. After HRF image acquisition, the retinal vasculature was perfused with fluorescein isothiocyanate for fluorescence microscopy. Using the standard HRF software and a 10×10 pixel measurement window, flow rates were measured from a retinal artery, vein, arteriole, venule, and the retinal capillary bed and a capillary-free-zone. The relationship between HRF measured flow and perfusion flow in the different measurement locations was determined. At zero perfusion flow the measured HRF flow was consistently greater than zero (∼170 arbitrary units (AU)), and not significantly different at each measurement location except for the retinal vein, which had a significantly higher HRF flow value (∼230 AU). At higher perfusion flow rates the flow signal from the larger vascular elements (arteries and veins) increased rapidly thereafter to reach several thousand AU at a total perfusate flow of 50 μl min −1 and increased less rapidly at higher flow rates. In arterioles, the HRF flow was more linear over a broader range of perfusate flow rates but the peak flow signal was an order of magnitude smaller than that from the retinal artery. Both the linearity and magnitude of the flow signal in venules was less than that in arterioles. In capillary areas and in the capillary free zone, the HRF flow showed only a very weak relationship to perfusion flow when compared to the background noise. The choice of location for HRF flow analysis greatly influences the ability of the technique to measure changes in retinal blood flow. The major arteries and veins provide the strongest signal and greatest signal to noise ratio. However, the retinal arterioles produce an HRF signal that is more linear over a wider range of perfusate flow rates.