Yasuhiro Tamaki

Choroidal circulation in diabetic patients.

Purpose To evaluate choroidal circulatory changes in diabetic patients with and without background diabetic retinopathy (BDR) by measuring the retrobulbar circulation with colour Doppler imaging (CDI).Methods CDI was used to measure circulatory parameters of the PCA (posterior ciliary artery), CRA (central retinal artery), OA (ophthalmic artery) and the respective veins in 73 diabetic patients and 22 controls in a sitting posture. Among the diabetic patients, 38 patients were without diabetic retinopathy (NDR) and 35 had BDR. A non-parametric Kruskal-Wallis test with a Dunn correction was used for data analysis.Results End-diastolic velocity (EDV) in the PCA was decreased (2.55 ± 0.80 cm/s) and resistivity index (RI) in the PCA was increased (0.70 ± 0.08) in BDR patients compared with the control patients EDV (3.23 ± 1.08 cm/s, p = 0.01) and RI (0.62 ± 0.06, p = 0.0003). RI in the CRA was significantly higher in the BDR group (0.74 ± 0.09) than in the control group (0.68 ± 0.08, p = 0.006). RI in the OA was significantly higher in the BDR group (0.87 ± 0.06) compared both with the NDR group (0.83 ± 0.07) and with the control group (0.81 ± 0.06; p = 0.007, p = 0.004). NDR patients had a significantly higher RI in the PCA (0.67 ± 0.08) than control patients (0.62 ± 0.06, p = 0.01, while the CRA RI (0.71 ± 0.09) did not show significant differences from the control group (0.69 ± 0.08, p = 0.32). Decreased EDV in the CRA was detected in NDR patients (2.16 ± 0.76 cm/s) compared with the controls (2.72 ± 0.92 cm/s, p = 0.007).Conclusion The results from this study suggest that not only the retinal but also the choroidal circulation is affected in NDR and BDR patients.

Topical Latanoprost and Optic Nerve Head and Retinal Circulation in Humans

The purpose of the present study was to study the effect of a single instillation of latanoprost on the human optic nerve head (ONH) and retinal circulation. Using laser-speckle tissue blood flow analysis, normalized blur (NB; a quantitative index of tissue blood velocity) was measured every 0.125 sec at a temporal ONH site free of visible surface vessels. Measurements were averaged for 3 cardiac cycles (NB(ONH)). Color Doppler Imaging (CDI) was also used to evaluate peak systolic blood velocity (PSV), endo-diastolic velocity (EDV), and resistive index (RI) in the central retinal artery (CRA) and mean blood velocity (MV) in the central retinal vein (CRV). One drop of 0.005% latanoprost was instilled into one eye and its vehicle into the other in eleven healthy volunteers in a double-blinded manner. Measurements of bilateral NB(ONH), CDI parameters, intraocular pressure (IOP), blood pressure (BP), and pulse rate (PR) were performed before, and 45, 90, 180, and 270 min after instillation. After a single instillation of latanoprost or the vehicle, there was no significant bilateral difference throughout the experimental period. The difference in NB(ONH) between that before and at each time point of measurement (delta NB(ONH)) in the latanoprost-treated eyes was significantly higher between 45 and 270 min after instillation than that in vehicle-treated eyes (P = 0.0003 to 0.0156); ANOVA for repeated measurements also revealed significant difference between both eyes (P < 0.00001). BP, PR, and NB(ONH) in the eye that received only the vehicle, PSV, EDV, and RI in the CRA in both eyes, and MV in the CRV in both eyes changed little. Tissue blood velocity in the ONH increased at least temporarily following a single instillation of topical latanoprost. Although the mechanism of the increase is unclear, the effects of latanoprost on ONH tissue circulation in humans may have clinical implications.

Effective accumulation of polyion complex micelle to experimental choroidal neovascularization in rats

Exudative age‐related macular degeneration, characterized by choroidal neovascularization (CNV), is a major cause of visual loss. In this study, we examined the distribution of the polyion complex (PIC) micelle encapsulating FITC‐P(Lys) in blood and in experimental CNV in rats to investigate whether PIC micelle can be used for treatment of CNV. We demonstrate that PIC micelle has long‐circulating characteristics, accumulating to the CNV lesions and is retained in the lesion for as long as 168 h after intravenous administration. These results raise the possibility that PIC micelles can be used for achieving effective drug targeting to CNV.

Retrobulbar circulation in patients with age-related maculopathy.

Purpose To investigate retrobulbar circulation in stages of age-related maculopathy (ARM) and in normal fellow eyes of patients with unilateral exudative ARM.Methods Color Doppler Imaging was used to measure circulatory parameters (peak-systolic velocity—PSV, end-diastolic velocity—EDV, pulsatility index—PI and resistivity index—RI) in the central retinal, posterior ciliary and ophthalmic arteries of 44 patients with age-related maculopathy (ARM) and 32 control subjects. Patients with ARM consisted of 11 with early ARM and 33 with late ARM. Twenty-one patients from the exudative ARM group were also included in a study of unilateral exudative ARM circulation.Results In the study of patients with ARM divided into stages, the PI and RI in the posterior ciliary artery of patients with late ARM were significantly higher than that of the control group (P = 0.0064; P = 0.0124). In the early ARM group, circulatory parameters did not differ significantly from those of the control group.In the study of unilateral exudative ARM, the affected eye showed significantly higher RI, as compared to the control group (P = 0.0157), and the fellow eye had significantly decreased EDV as compared to the control group (P = 0.0164). There was no significant difference in circulatory parameters between the affected and normal fellow eyes of patients with unilateral exudative ARM.Conclusion PI and RI in patients with late ARM and EDV in fellow eyes of patients with unilateral exudative ARM showed significant changes in the posterior ciliary artery compared to normal controls. Altered circulation in the posterior ciliary artery may be involved in the pathogenesis of ARM.

Effect of Topical Unoprostone on Circulation of Human Optic Nerve Head and Retina

The purpose of the present study was to study the effect of topical unoprostone on the circulation of human optic nerve head (ONH) and retina in normal subjects. Using laser-speckle tissue blood flow analysis, normalized blur (NB), a quantitative index of tissue blood velocity, was measured every 0.125 sec at a temporal ONH site, free of visible surface vessels. Measurements were averaged for 3 cardiac cycles (NB(ONH)). Color Doppler imaging (CDI) was also used to evaluate peak systolic blood velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) in the central retinal artery (CRA) and mean blood velocity (MV) in the central retinal vein (CRV). For baseline comparison (Day 0), recordings of bilateral NB(ONH) and intraocular pressure (IOP), blood pressure (BP), and pulse rate (PR) were recorded in healthy volunteers before, and 45, 90, 180, and 270 min after instillation of one drop of unoprostone vehicle. On Day 1 (the day after baseline measurements), and twice daily for 7 days, one drop of 0.12% unoprostone was instilled into one eye and its vehicle into the other in a double-blinded manner. Measurements as on Day 0 were recorded on Days 1 and 7. CDI measurements were performed before and at 45 and 180 min after morning instillation on Days 1 and 7. During baseline recordings, there were no significant changes in any parameters. After administration of topical unoprostone, IOP was significantly lower bilaterally with more reduction in the unoprostone-treated eyes on Day 7. On Day 7, the NB(ONH) of the unoprostone-treated eyes was significantly higher 45 min after instillation than baseline (P = 0.035 with Bonferronis correction). Analysis of variance for repeated measurements also revealed significant difference between Day 0 and Day 7 (P = 0.0017). BP, PR, NB(ONH) in the eye that received only the vehicle, PSV, EDV, and RI in the CRA in both eyes, and MV in the CRV in both eyes changed little. Tissue blood velocity in the ONH increased, at least temporarily, following instillation of unoprostone twice daily for 7 days. Although the clinical implication of the increase is unclear, the effects of topical unoprostone on human ONH circulation deserve further consideration.

Transpupillary thermotherapy for treatment of exudative age-related macular degeneration in Japanese patients

AbstractPurpose To report the therapeutic outcome of transpupillary thermotherapy (TTT) for subfoveal choroidal neovascularizarion (CNV) in brown retina using a diode-laser with the setting of lower energy level compared to the previous studies on light-pigmented Caucasian patients.Methods A total of 19 subfoveal CNVs in 18 patients were treated with TTT. The power of diode-laser was set 160u2009mW for 1.2u2009mm beam, 270u2009mW for 2.0u2009mm beam, and 400u2009mW for 3.0u2009mm beam, and the laser was delivered for 1u2009min through a slit-lamp mounted-delivery system. Patients were followed up for a mean of 8.8 months (4–12 months). Visual acuity and the fundus change as judged by funduscopic examination and simultaneous fluorescein and indocyanine green angiography were evaluated. Visual acuity was measured by a Japanese standard Landolt visual acuity chart and converted to logarithm of the minimal angle resolution (logu2009MAR) visual acuity for statistical analysis. Improvement or decline in vision was defined as change of more than 0.2 in logu2009MAR visual acuity.Results In eyes with minimally classic or occult only CNV, visual acuity improved in two eyes (18%) stabilized in seven eyes (64%) and worsened in two eyes (18%). In eyes with predominantly classic CNV, visual acuity improved in two eyes (25%), stabilized in four eyes (50%) and worsened in two eyes (25%). In all, 15 (84%) eyes of all studied subjects had improvement in exudation. Two (11%) and one (5%) eye(s) were noted to have a significant post-treatment haemorrhage and retinal pigment epithelial tear, respectively.Conclusion In patients with brown retinal colour, the treatment outcome of TTT was comparable to that of light-pigmented Caucasian patients with approximately half the laser power energy. Further randomized control studies are warranted.

Validation of scanning laser Doppler flowmetry for retinal blood flow measurements in animal models

Purpose. To evaluate the validity of scanning laser Doppler flowmetry in retinal blood flow measurement in vivo using rabbit and monkey eyes and the microsphere technique. Methods. A commercially available scanning laser Doppler flowmeter (SLDF), pigmented rabbits and cynomolgus monkeys were used. In rabbits, SLDF measurements at a retinal field approximately one papillary diameter away from the optic nerve head where discrete retinal vessels were not visible (vascularized medullary field) were compared with those at a field approximately one papillary diameter below the ONH (nonvascularized extramedullary field). The effect of intraocular pressure (IOP) on SLDF measurements was studied by elevating the IOP manometrically in both rabbit and monkey eyes. Retinal and choroidal blood flow measurements using the microsphere technique and an SLDF measurements were performed simultaneously in the same rabbit eye before and 30min after 0.3mg/kg intravenous injection of lomerizine, a calcium antagonist, or intravitreal injection of 20 µl of 10 -6 M endothelin-1. Results. The blood flow measurement with an SLDF (SLDF flow) obtained from the medullary field in rabbits were 304 ± 63 in an arbitrary unit (n = 24), while 392 ± 39 in the extramedullary field. SLDF flow did not significantly changed by changes in IOP when it was below 50mmHg, significantly decreasing with IOP elevation above that level in rabbits and a similar tendency was also seen in monkeys. It showed a significant correlation with retinal blood flow measured by the microsphere technique (r = 0.596, P < 0.0001) in rabbits; no correlation was found with the choroidal blood flow rate (r = 0.021, P > 0.1). Conclusions. SLDF measurements is thought to mainly reflect retinal circulation in rabbits and monkeys.

Fine retinal crystalline deposits observed by confocal scanning laser ophthalmoscopic examination using infrared light

Biettis crystalline retinopathy is a tapetoretinal degeneration characterised by numerous tiny sparkling yellow-white spots mainly located in the deeper layer of the posterior pole retina.1 Since crystalline deposits tend to become small and decrease in number over time,2,3 the fundus appearance becomes indistinguishable from other retinal dystrophies with time.4 The advent of confocal scanning laser ophthalmoscope (SLO) with infrared light has enabled high sensitive examination of the deep layer of the retina.5 We studied the deep retinal abnormalities in a case with a typical Biettis crystalline retinopathy and in another case with myopic chorioretinal atrophy throughout the posterior pole. Consequently, we detected numerous fine crystalline deposits in both cases, which were not detected with other funduscopic examinations.nn### Case 1nnA 52 year old man was referred to our hospital by his ophthalmologist who found an abnormal fundus appearance. There was no consanguinity. Best corrected visual acuity was 20/24 right eye and 20/50 left eye. No abnormalities were found in the anterior segment and media. Fine crystalline deposits were not detected in the corneal stroma of either eye. Funduscopic examination revealed numerous fine reflective crystalline deposits throughout the posterior pole and mid-peripheral retina of both eyes. Most of these deposits were in the deep retina and subretina but some deposits …

Fluorescein angiography-guided indocyanine green angiography for the detection of feeder vessels in subfoveal choroidal neovascularization.

AbstractAims To compare the newly devised fluorescein angiography (FA) - guided indocyanine green angiography (ICGA) with conventional ICGA for detecting feeder vessels in subfoveal choroidal neovascularization (CNV).Methods The detection of feeder vessels was attempted in 86 AMD patients with subfoveal CNV: 44 (age 70.4±4.5u2009years) underwent conventional ICGA (control group) and 42 (age 70.9±4.0u2009years) underwent an FA-guided ICGA (FA-guided group) using a double-detector scanning laser ophthalmoscope (SLO). In the control group, indocyanine green (ICG) was injected simultaneously with fluorescein. The patients were instructed to gaze forward localizing the fovea at the centre. In the FA-guided group, fluorescein sodium was injected a few minutes prior to ICG, and the patients were instructed to fixate in the appropriate direction by referring to the ongoing FA on the monitoring screen. In both groups, a 20° visual angle was used to capture good images of feeder vessels in ICGA and, in case ICGA missed the first images of the entire CNV filling, an additional injection of ICG was given in the late phase to record the choroidal filling again. The overall detection rate, single-injection detection rate, double-injection rate and examination time were analysed using Fishers direct exact probability test or Mann–Whitneys U-test.Results There was no significant difference in the overall detection of feeder vessels between the two groups (50% in the control group and 52.3% in the FA-guided group; P=0.49 with Fishers direct exact probability test). However, in the FA-guided group, the single injection detection rate was significantly higher (45.1 and 15.9%, respectively; P<0.001 with Fishers direct exact probability test); significantly less double injections were required (7.1 and 50%, respectively; P=0.003 with Fishers direct exact probability test); and significantly shorter examination times were needed (9.6±3.7 and 14.1±6.8u2009min, respectively; P=0.02 with Mann–Whitneys U-test).Conclusion FA-guided ICGA is effective for detecting feeder vessels of subfoveal CNV, minimizing the amount of ICG injected and the examination time compared to conventional ICGA.

Effects of Kallidinogenase on Ocular Tissue Circulation in Rabbits

The purpose of this study is to evaluate the effects of kallidinogenase, a tissue kallikrein, on tissue circulation in the optic nerve head (ONH), choroid and retina. Kallidinogenase (1.0 IU/kg) or saline was injected intravenously into urethane-anesthetized rabbits, and the normalized blur value (NB), a quantitative index of in vivo tissue blood velocity, was measured in the ONH, choroid and retina before and for 90 minutes after injection, using the laser speckle method. The difference in NB values in the kallidinogenase group was significantly higher compared with that in the control group in the choroid (p < 0.05) and retina (p < 0.05, ANOVA of repeated measurements). In the ONH, however, there was no significant difference between the kallidinogenase group and the control group except transient increment 10 min after drug administration (p < 0.01, unpaired t-test). On the other hand, systemic condition parameters and intraocular pressure showed no intergroup difference significantly except for a transient decrease in blood pressure and increase in pulse rate in the kallidinogenase groups. Kallidinogenase increased blood velocity, and probably blood flow, in the choroid and retina of rabbits.