Hak Sung Chung

Ocular haemodynamic responses to induced hypercapnia and hyperoxia in glaucoma

Aim: To determine the ocular haemodynamic response to gas perturbations in glaucoma. Methods: Intraocular pressure (IOP), systemic systolic and diastolic blood pressure (SBP and DBP), and retrobulbar blood flow velocities, measured by colour Doppler imaging (CDI), were recorded at two visits. CDI was used to measure peak systolic and end diastolic velocities (PSV and EDV) and resistance index (RI) in the ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary arteries (SPCAs). At the first visit, measurements were taken at baseline (B1: breathing room air) and during isoxic hypercapnia (end tidal PCO2 increased 15% above baseline) in 16 normal subjects and 12 patients with glaucoma. On another day, measurements were repeated at a second baseline (B2) and during hyperoxia (100% oxygen breathing) for 15 normal subjects and 13 glaucoma patients. Baseline systemic data were compared using paired t tests; REANOVA was performed to compare group differences at baseline and to determine the vessel response to each condition. Fisher’s LSD was used for post hoc comparison. Results: Baseline OA PSV was lower for the glaucoma than for the normal group (p = 0.047); the groups were otherwise similar at baseline. IOP demonstrated no response to hypercapnia, but reduced during hyperoxia for both the normal subjects (p<0.0001) and glaucoma patients (p = 0.04). During hypercapnia, SBP increased in normal subjects (p = 0.03) and glaucoma patients (p = 0.01); DBP increased in normal subjects (p = 0.021). There was a corresponding increase in ocular perfusion pressure (OPP) for normal subjects (p = 0.01) and glaucoma subjects (p = 0.028), and as a result OPP was included as a covariate in the REANCOVA model. Hypercapnia resulted in increased PSV in the CRA of normal subjects (p = 0.035) and increased PSV and EDV in the SPCAs of glaucoma patients (p = 0.041 and p = 0.030 respectively). Hyperoxia resulted in reduced PSV and EDV in the ophthalmic arteries of normal subjects only (p = 0.001 and 0.031 respectively). Conclusions: These findings suggest the presence of relative vasoconstriction in glaucoma patients, which is at least partially reversed by hypercapnia.

Peripapillary retinal blood flow in normal tension glaucoma

AIMS To determine if normal tension glaucoma (NTG) patients differ from age matched controls in blood flow to the peripapillary retina, as measured with confocal scanning laser Doppler flowmetry (cSLDF; “Heidelberg retinal flowmetry”). METHODS 12 NTG patients and 12 age matched controls were compared using (a) 10 × 10 pixel boxes (the instrument default sample size), taken from the nasal and temporal peripapillary retina, (b) the average from two of these boxes, and (c) every qualifying pixel within the peripapillary retina. RESULTS Patients and controls did not differ in blood flow measured using the default sample from a single 10 × 10 pixel box, placed in either the temporal or nasal peripapillary retina, or expressed as the average from these two boxes. However, in histograms using every pixel from the peripapillary retina, NTG patients displayed significantly higher percentages of minimal flow pixels (defined as less than one arbitrary unit of flow: 30% v 19%, p <0.01), and significantly lower flow in the 25th, 50th, and 75th percentile flow pixel (each p <0.05) than did age matched controls. CONCLUSION NTG is characterised by reduced blood flow in the peripapillary retina, a result suggesting that blood flow deficits accompany, and perhaps may contribute to, disease development in these patients.

Glaucoma patients demonstrate faulty autoregulation of ocular blood flow during posture change.

BACKGROUND/AIMS Autoregulation of blood flow during posture change is important to ensure consistent organ circulation. The purpose of this study was to compare the change in retrobulbar ocular blood flow in glaucoma patients with normal subjects during supine and upright posture. METHODS 20 open angle glaucoma patients and 20 normal subjects, similar in age and sex distribution, were evaluated. Blood pressure, intraocular pressure, and retrobulbar blood velocity were tested after 30 minutes of sitting and again after 30 minutes of lying. Retrobulbar haemodynamic measures of peak systolic velocity (PSV), end diastolic velocity (EDV), and resistance index (RI) were obtained in the ophthalmic and central retinal arteries using colour Doppler imaging (CDI). RESULTS When changing from the upright to supine posture, normal subjects demonstrated a significant increase in OA EDV (p = 0.016) and significant decrease in OA RI (p = 0.0006) and CRA RI (p = 0.016). Glaucoma patients demonstrated similar changes in OA measures of EDV (p = 0.02) and RI (p = 0.04), but no change in CRA measures. CONCLUSION Glaucoma patients exhibit faulty autoregulation of central retinal artery blood flow during posture change.

Heidelberg retinal flowmetry: factors affecting blood flow measurement

AIMS To evaluate factors affecting Heidelberg retinal flowmeter (HRF) measurements of retinal and optic nerve head blood flow in human subjects. METHODS The angle of incidence between laser beam and fundus, and camera distance from the eye, were evaluated for their effect upon measures of blood volume, velocity, and flow in a single 100 × 100 × 400 μm volume of temporal peripapillary retinal tissue in normal volunteers. Both intra and intersession reproducibility of these measures were studied. Intersession data were obtained by taking one image per week for 4 weeks. Finally, the intersession haemodynamic data were examined in the entire image (640 × 2560 × 400 μm), using histograms of pixel by pixel blood flow. RESULTS Measures of blood volume, velocity, and flow from a single anatomical site were unaffected by laser beam to fundus angle of incidence (n = 12). As camera distance from the eye was increased (from 2 to 5 to 7 cm), flow measurements showed increasing individual changes, despite unaltered measured vessel lengths and constant overall mean flow (n = 14). The coefficient of variation for two intrasession images of optic nerve head blood flow averaged 7% (n = 20); in contrast, the 4 week intersession coefficient of variation averaged 30% (n = 15). Intersession reproducibility was increased by using flow histograms from the entire image: the coefficients of variation averaged 16% for total flow and 17% for flow in the pixel of median flow. CONCLUSION HRF measures of flow are independent of the laser beam to fundus angle of the incidence and dependent upon camera distance from the eye. Intersession reproducibility is best using pixel by pixel analysis of the entire image.

A comparative study of betaxolol and dorzolamide effect on ocular circulation in normal-tension glaucoma patients

OBJECTIVE To determine whether dosages of a selective beta-blocking agent (betaxolol) and a topical carbonic anhydrase inhibitor (dorzolamide), sufficient to significantly lower intraocular pressure (IOP), have similar or disparate impact on the retinal and retrobulbar circulation. DESIGN Counterbalanced crossover, with open-label use of medications. PARTICIPANTS Nine persons with normal-tension glaucoma (NTG). INTERVENTION After a 3-week drug washout, NTG patients were studied after 1 month of treatment with either dorzolamide or betaxolol, with determinations of IOP and retinal and retrobulbar hemodynamics. MAIN OUTCOME MEASURES At baseline and after treatment with each drug, retinal arteriovenous passage time was determined by scanning laser ophthalmoscopy after fluorescein dye injection, and flow velocities in the central retinal and ophthalmic arteries were measured with color Doppler ultrasonography imaging. RESULTS Betaxolol and dorzolamide each lowered IOP significantly, with these changes apparent and maximal after 2 weeks (each P < 0.05). In contrast, dorzolamide (but not betaxolol) accelerated arteriovenous passage of fluorescein dye in the inferior temporal quadrant of the retina (P < 0.05). Neither drug affected arteriovenous passage in the superotemporal retina or any aspect of central retinal or ophthalmic artery flow velocity after either 2 or 4 weeks. CONCLUSIONS Although both dorzolamide and betaxolol are effective ocular hypotensive agents and their topical instillation leaves retrobulbar hemodynamics unaltered, dorzolamide alone accelerates inferotemporal retinal dye transit.

Choroidal perfusion perturbations in non-neovascular age related macular degeneration.

Aim: Choroidal perfusion, affected in age related macular degeneration (AMD), is difficult to objectively assess given the overlying retinal circulation. This study more objectively compared choroidal perfusion parameters in a group with non-neovascular AMD to an unaffected age matched control group. Methods: 21 non-neovascular AMD subjects and 21 age matched control subjects without evidence of AMD underwent assessment of their choroidal blood flow in a case-control study. Scanning laser ophthalmoscope indocyanine green (ICG) angiograms were analysed by a new area dilution analysis technique. Four areas in the perifoveal region and two areas in the temporal peripapillary retina were evaluated by producing a graph of intensity of fluorescence of each area over time. The mean of the filling times and the heterogeneity of the filling times were assessed. Results: The means of the filling times within the perifoveal regions and the hetereogeneity of the filling times between regions within the same eyes were significantly greater in the AMD patients compared with the control subjects. Conclusions: Delayed and heterogeneous filling of the choroid was objectively demonstrated in eyes with non-neovascular AMD compared with age matched controls without evidence of AMD, using an area dilution analysis technique applied to ICG angiography.

Comprehensive assessment of retinal, choroidal and retrobulbar haemodynamics during blood gas perturbation

Abstract · Background: A study was performed to evaluate the effect of isoxic hypercapnia on ocular haemodynamics using colour Doppler imaging (CDI), scanning laser Doppler flowmetry (SLDF) and ocular blood flow (OBF) tonography. · Methods: Measurements were taken for one eye of each of 14 healthy subjects (mean age 27±6 years) during breathing of room air and then during isoxic hypercapnia (breathing CO2 and room air). Using CDI, blood flow velocities and resistance indices were determined for the ophthalmic artery (OA), central retinal artery (CRA) and short posterior ciliary arteries (SPCAs). Using SLDF, a 10×10 pixel frame was used to measure blood flow, volume and velocity in each quadrant of the peripapillary retina. Pulsatile ocular blood flow (POBF) was measured using the OBF tonograph. · Results: Using CDI, peak systolic and end diastolic velocities increased and resistance index decreased significantly in the SPCAs during hypercapnia. Using SLDF, blood flow, volume and velocity increased significantly during hypercapnia in the superior temporal quadrant of the peripapillary retina. No significant difference was observed between baseline and hypercapnia for POBF. · Conclusions: Isoxic hypercapnia resulted in an increase in peripapillary retinal and SPCA blood flow parameters as determined by SLDF and CDI respectively. This implies the presence of autoregulatory activity in these vasculatures. These findings may be of significance in the pathogenesis of ocular disease such as glaucoma where autoregulation is thought to be compromised.

Ocular haemodynamics in glaucoma associated with high myopia.

AbstractThe ocular blood flow of a group of high myopic and glaucomatous eyes has been investigated by means of the Color Doppler Imaging (CDI) technique, comparing the results with those of some very myopic eyes without glaucoma, some non-myopic glaucomatous eyes and with a control group. The Ophthalmic Artery (OA), the Short Posterior Ciliary Arteries (SPCAs) and the Central Retinal Artery (CRA) were considered. For every vessel, peak systolic velocity (SV), end-diastolic velocity (DV) and the Pourcelot Resistivity Index were studied. The statistical analysis was performed by means of t-test according to Bonferroni procedure for multiple comparisons. The authors registered in the group of eyes with glaucoma associated with very severe myopia some abnormalities of the OA blood flow systolic velocity which might be interpreted as a vascular risk factor for the pathogenesis of the glaucomatous opticneuropathy; these abnormalities are more severe in glaucoma patients with high myopia than in anage-matched group of glaucoma patients without myopia.

New neuroretinal rim blood flow evaluation method combining Heidelberg retina flowmetry and tomography

AIM Accurate Heidelberg retina flowmeter (HRF) measurements require correct manual setting of the HRF photodetector sensitivity. The neuroretinal rim produces a weak signal relative to the peripapillary retina. A newly developed HRF alignment and sensitivity protocol, capable of accurate rim measurement, was investigated. METHODS 18 eyes of nine healthy volunteers were examined by HRF. Three images of each eye were taken using three different imaging methods. Method 1: a conventional image (optic nerve head centred image with photodetector sensitivity optimised for the strong signal from the peripapillary retina); method 2: the setting of method 1 with photodetector sensitivity optimised for the weak signal from the rim; and method 3: the setting of method 2 with the temporal rim margin tangent to the lateral image border to remove the overpowering signal from the temporal peripapillary retina. The neuroretinal rim was defined by the Heidelberg retina tomograph (HRT). Blood flow and reflectivity values (DC component) in the rim area were compared for the three methods using pointwise analysis. Coefficients of variation of repeated measurements in 12 subjects have been calculated for method 3. RESULTS The neuroretinal rim area measured by method 1 had a significantly lower brightness compared with method 2 and 3 (p=0.0002 and p=0.0002, respectively). Method 2 provided proper sensitivity for the weak signals of the rim area based on rim tissue DC values; however, this sensitivity setting was too high for the strong signal from the peripapillary retina. Method 3 avoided the strong peripapillary signal with the proper signal from the rim and provided significantly higher flow values of the rim area at 75 and 90 percentile pixels (p=0.0065 and p=0.0038 respectively) compared with method 2. Interobserver repeatability ranged from 16.85% to 21.96% for the different parameters. CONCLUSIONS Method 3 provides an accurate and reproducible flow measurement of the neuroretinal rim area through proper sensitivity for the weak rim signal, alignment, and removal of the strong temporal signal from the image. This new method is recommended to improve accuracy of blood flow measurement in the neuroretinal rim.

Blood flow per unit retinal nerve fibre tissue volume is lower in the human inferior retina

Aim: To determine if perfusion per unit tissue volume of retinal nerve fibre layer and optic nerve head in the inferior sector is lower than in the superior sector. Methods: Heidelberg retinal tomogram (HRT) for topographic measurement of optic nerve head and retinal nerve fibre layer and Heidelberg retinal flowmeter (HRF) for retinal blood flow were performed on 19 normal healthy subjects. Measurements from the superior and inferior sectors were compared. The perfusion/nerve fibre ratio (PNR); the blood flow per unit retinal nerve fibre tissue volume, was calculated in each sector with a formula; HRF flow measurements divided by HRT measurements. Results: Retinal nerve fibre layer thickness in the inferior retina was significantly higher than in the superior retina (p<0.05). There were, however, no differences in retinal blood flow between the superior and inferior retinal sectors. The PNR in the inferior sector were significantly lower than in the superior sector (p=0.047 for HRF mean flow/rim volume and p = 0.0282 for HRF 75th percentile flow/rim volume). Conclusions: The inferior sector of retinal nerve fibre layer and optic nerve head may have lower blood flow per unit nerve tissue volume compared to the superior sector. This result suggests that the inferior sector is more vulnerable to elevated intraocular pressure (IOP) and ischaemic insults in glaucomatous optic neuropathy.