Fumihiko Mori

Alteration of choroidal circulation in the foveal region in patients with type 2 diabetes

Aim: To investigate changes in choroidal blood flow (CBF) in the foveal region in patients with type 2 diabetes. Methods: Laser Doppler flowmetry was used to determine the CBF in the foveal region in 70 patients with type 2 diabetes and 36 age and sex matched healthy subjects (control group). The patients were classified into three groups: 33 patients (33 eyes) with no diabetic retinopathy (NDR), 20 patients (20 eyes) with non-proliferative diabetic retinopathy and no macular oedema (NPDR/MO−), and 17 patients (17 eyes) with NPDR and MO (NPDR/MO+). Optical coherence tomography was also used to measure the foveal thickness. Results: The group averaged CBF values were 13.5 (4.9), 9.4 (2.5), 10.8 (4.8), and 5.6 (2.0) (arbitrary units) in the control, NDR, NPDR/MO−, and NPDR/MO+ groups, respectively. The group averaged CBF values in the NDR group decreased (30.2%; p<0.01) compared with the control group. The average CBF value in the NPDR/MO+ group was also significantly lower (48.2%; p<0.01) compared with that in the NPDR/MO− group. Conclusion: The CBF in the foveal region significantly decreases in patients with diabetes, especially those with macular oedema.

Pulsatile ocular blood flow study: decreases in exudative age related macular degeneration

BACKGROUND Pulsatile ocular blood flow (POBF) is a parameter for evaluating choroidal blood flow. POBF in the patients with non-exudative and exudative age related macular degeneration (AMD) was investigated. METHODS POBF, pulse amplitude (PA), systolic and diastolic blood pressures, intraocular pressure (IOP), refractive error, and axial length were compared among 10 patients with non-exudative AMD, 11 patients with exudative AMD, and 69 age matched controls. A Langham OBF computerised tonometer was used with the participants in the sitting position to measure POBF and PA. RESULTS No significant differences were found in age, systolic and diastolic blood pressures, IOP, or refractive error between patients with exudative and non-exudative AMD and the control subjects. In the patients with exudative AMD the POBF (median, 372.7 μl/min) and PA (median, 1.2 mm Hg) were significantly lower than in the patients with non-exudative AMD (median, 607.0 μl/min (p = 0.02) and 2.2 mm Hg (p = 0.04), respectively) and control subjects (median, 547.4 μl/min (p = 0.01) and 2.0 mm Hg (p = 0.01), respectively). CONCLUSIONS These data show that the POBF and PA in the patients with exudative AMD are lower than in the patients with non-exudative AMD and normal subjects. Decreased choroidal blood flow may have a role in the development of choroidal neovascularisation in AMD.

Constitutive nitric oxide synthase is associated with retinal vascular permeability in early diabetic rats

Abstract.Aims/hypothesis: We investigated the association between vascular permeability and constitutive nitric oxide synthase in rats with diabetes for a short duration (2 weeks). Methods: Retinal vascular permeability was evaluated in rats with diabetes induced by streptozotocin using vitreous fluorophotometry and a small animal adapter. We carried out in situ hybridization and semi-quantitative reverse transcription–polymerase chain reaction to study the expression of endogenous constitutive nitric oxide synthase mRNA in diabetic retinas. We also examined changes in the protein expression of constitutive nitric oxide synthase in diabetic retinas using immunohistochemistry and Western blotting. Results: Retinal vascular permeability was significantly higher in diabetic rats (median, 1.09 arbitrary unit) compared with control rats (median, 0.69 arbitrary unit) (p < 0.05). The expression of both neuronal nitric oxide synthase (NOS) and endothelial nitric oxide synthase mRNA was higher in diabetic retinas than in the retinas of control rats as determined by in situ hybridization and reverse transcription-polymerase chain reaction. Immunohistochemistry and Western blotting also showed that neuronal nitric oxide synthase increased in diabetic retinas. The immunohistochemistry of endothelial nitric oxide synthase indicated that non-vessel tissues increased in diabetic retinas while retinal vessels weakened. Western blotting showed that the amount of endothelial nitric oxide synthase increased. Conclusion/interpretation: These results suggest that increases in both constitutive NOSs (nNOS and eNOS) could be associated with retinal vascular permeability and that NOS is associated with clinical vascular dysfunction in the early stages of diabetes. [Diabetologia (2001) 44: 1043–1050]

Scotoma and Fixation Patterns Using Scanning Laser Ophthalmoscope Microperimetry in Patients With Macular Dystrophy

PURPOSE We used scanning laser ophthalmoscope microperimetry to evaluate the retinal scotoma and the fixation points in the patients with macular dystrophy. METHODS We studied 10 eyes of five patients with macular dystrophy (three patients with cone dystrophy and two patients with Stargardt disease). The mean patient age was 37 years (range, 13 to 64 years). An estimation of scotoma and fixation points on the retina was performed using scanning laser ophthalmoscope microperimetry. RESULTS All 10 eyes (100%) had one of two types of dense scotoma: type one was a dense ring scotoma (five eyes, 50%), and type two was a dense central scotoma (five eyes, 50%) that included the center of the fovea. In all eyes with a dense ring scotoma, the fixation points were stable and did not shift. In all eyes with a dense central scotoma, the fixation shifted. The logarithm of minimal angle of resolution of the visual acuity in the eyes with the dense central scotoma was significantly worse than that of eyes with the dense ring scotoma type (P =.005). CONCLUSIONS Scanning laser ophthalmoscope microperimetry findings demonstrate two types of dense scotoma (dense ring scotoma and dense central scotoma) in the patients with macular dystrophy. The two types of dense scotoma affect the shifting of the fixation points and the stability of fixation and may result in the difference in visual acuity in the patients with macular dystrophy.

Use of scanning laser ophthalmoscope microperimetry in clinically significant Macular edema in type 2 diabetes mellitus

PURPOSE We used scanning laser ophthalmoscope (SLO) microperimetry to evaluate scotomas in patients with clinically significant diabetic macular edema (CSME) in type 2 diabetes mellitus. METHODS We studied 19 patients (mean age = 63 years; range, 45-78 years) (19 eyes). SLO microperimetry was performed in all eyes. We divided patients into three groups as follows: dense scotoma, relative scotoma, and no scotoma. The following variables were documented: age; duration of diabetes, hemoglobin A(1c) levels; logarithm of the minimum angle of resolution (Log(MAR)) visual acuity; refractive power; a history of panretinal photocoagulation; presence or absence of proliferative diabetic retinopathy, vitreomacular separation, and cystoid changes; the type of macular edema; and stability of fixation. All variables were compared in the three groups. RESULTS We identified 4 eyes (21.1%) with dense scotoma, 10 (52.6%) with relative scotoma, and 5 (26.3%) with no scotoma. There were significant differences in log(MAR) visual acuity among those with dense scotoma (1.4 +/- 0.5), relative scotoma (0.6 +/- 0.2), and no scotoma (0.2 +/- 0.3) (P <.05), and in the prevalence of cystoid changes, diffuse edema, and unstable fixation among those with dense scotoma (75%, 75%, and 100%, respectively), relative scotoma (20%, 30% and 50%, respectively) and no scotoma (0%, 0% and 0%, respectively) (P <.05). CONCLUSIONS Macular scotoma was observed by SLO microperimetry in 74% of the patients in this study. A scotoma in CSME is related to the formation of cystoid changes and the type of macular edema. In eyes with CSME in type 2 diabetes mellitus, a scotoma in the macula causes visual acuity impairment and unstable fixation.

Factors affecting pulsatile ocular blood flow in normal subjects

BACKGROUND The factors that influence pulsatile ocular blood flow (POBF) were evaluated in normal subjects. METHODS POBF was measured in 80 normal subjects using Langham OBF computerised tonometry. The effect of age, systolic and diastolic blood pressure, refractive error, intraocular pressure, and axial length on POBF was evaluated using multiple regression analysis. RESULTS The mean (SD) POBF value was 593.3 (203.6) μl/min (range 290.7–1201.6). Of all the independent variables in the model, only the axial length was statistically significant (p=0.008). The regression coefficient was negative, indicating that the axial length decreased with increasing POBF. CONCLUSIONS These data suggest that, in normal subjects, the POBF decreases as axial length increases. Choroidal blood flow may decrease as the axial length increases. The axial length may therefore be a major factor affecting POBF.

Inhibitory effect of losartan, an AT1 angiotensin II receptor antagonist, on increased leucocyte entrapment in retinal microcirculation of diabetic rats

Background: The effectiveness of losartan for the treatment of leucocyte entrapment in the retinal microcirculation of diabetic rats was evaluated quantitatively. Methods: After diabetes was induced by injection of streptozotocin (STZ), the rats were divided into two subgroups. The first subgroup (n = 6), received no medications; the second subgroup (n = 6) was given fresh drinking water supplemented with losartan (5 mg/kg/day) for 4 weeks. Six rats that were not injected with STZ or given medications served as controls. 4 weeks after intervention, leucocyte dynamics in the retina were observed using acridine orange digital fluorography. Leucocyte entrapment in the retina was compared among the three groups. Results: In the untreated diabetic rats, the number of trapped leucocytes (6.1 (SD 1.4) cells/mm2) increased significantly compared with control rats (2.8 (1.2) cells/mm2; p = 0.005) and diabetic rats treated with losartan (3.1 (0.9) cells/mm2; p = 0.0002). Conclusions: Losartan, an AT1 angiotensin II receptor antagonist, inhibited increased leucocyte entrapment in the diabetic retina. The authors demonstrated that losartan may have therapeutic efficacy in preventing development of diabetic retinopathy. Further clinical studies of the effect of the angiotensin receptor antagonist on preventing development of diabetic retinopathy are needed.

Peroxynitrite decomposition catalyst, FP15, and poly(ADP-ribose) polymerase inhibitor, PJ34, inhibit leukocyte entrapment in the retinal microcirculation of diabetic rats

Purpose. Oxidative and nitrosative stress and activation of poly(ADP ribose) polymerase (PARP) play a role in the pathogenesis of diabetic complications. We evaluated the effectiveness of the peroxynitrite decomposition catalyst, FP15, and the PARP inhibitor, PJ34, in the treatment of leukocyte entrapment in the retinal microcirculation of diabetic rats. Methods. Diabetes was induced in rats by intraperitoneal injection of 60 mg/kg of streptozotocin. Rats were divided into four groups: controls; untreated diabetes; diabetes treated with FP15 (10 mg/kg oral gavage twice daily) and diabetes treated with PJ34 (10 mg/kg oral gavage twice daily). All experiments were performed 4 weeks after initiation of treatment. Leukocyte entrapment in the retinal microcirculation was quantitatively evaluated in vivo with acridine orange digital fluorography. Results. The density of leukocytes trapped in the retinal microcirculation 30 minutes after dye injection was significantly greater in untreated diabetes (32.1 ± 4.7 cells/mm2) than in controls (11.3 ± 4.5 cells/mm2) (p < 0.05). Compared with untreated diabetes, the density of trapped leukocytes significantly decreased in diabetes treated with FP15 (14.5 ± 5.1 cells/mm2) (p < 0.0001) and diabetes treated with PJ34 (24.1 ± 4.2 cells/mm2) (p < 0.05). Conclusions. Treatment with FP15 and PJ34 decreased enhanced leukocyte entrapment in the retinal microcirculation during the early diabetic period. The current study suggests a role for peroxynitrite production and for PARP activation in the pathogenesis of retinal microvascular leukostasis in early diabetes.

Relation Between Plasma Nitric Oxide Levels and Diabetic Retinopathy

PurposeNitric oxide (NO) plays an important role in homeostatic vasodilation and the regulation of blood flow. On the other hand, excess release of NO causes various vascular complications. There are only a few reports on the relationship between plasma NO levels and microvascular complications, especially diabetic retinopathy (DR) in patients with type 2 diabetes. The purpose of this study was to determine the relationship between plasma NO levels and DR.MethodsIn a prospective study, blood samples were obtained from 36 patients with diabetes and no diabetic retinopathy (NDR), 43 patients with nonproliferative diabetic retinopathy (NPDR), 18 patients with proliferative diabetic retinopathy (PDR), and 40 subjects without diabetes mellitus, who served as controls. The levels of plasma NOx (nitrite and nitrate), the stable metabolites of NO, were measured by high-performance liquid chromatography with the Griess method.ResultsThe plasma NOx levels were 92.8 ± 16.0, 70.2 ± 6.8, 90.3 ± 9.1, and 53.8 ± 6.1 µmol/l in patients with NDR, NPDR, or PDR, and in the controls, respectively. The plasma NOx levels in the three diabetic groups were significantly higher than those in the control group (P < 0.05 in each case).ConclusionThe increased plasma NO levels in patients with type 2 diabetes indicate that NO may be associated with the pathogenesis of DR. Jpn J Ophthalmol 2006;50:465–468

Changes in blood-retinal barrier permeability in form deprivation myopia in tree shrews

To study the correlation between blood-retinal barrier (BRB) permeability and development of form deprivation (FD) myopia, FD was induced in tree shrews. The refractive error and the axial dimensions of the optical elements were measured. Ocular fluorescence was measured before and after fluorescein-Na injection. The inward permeability (P(in)) of the BRB was measured before and 15, 30, and 45 days after FD was induced. FD eyes became significantly myopic 15 days after FD was induced (P<0.01), and myopia progressed 45 days after FD was induced compared with untreated controls. Neither anterior chamber length nor lens thickness changed significantly. The vitreous chamber in FD eyes, however, was significantly elongated from 15 days after FD was induced (P<0.01) compared with controls. The P(in) ratio (P(in) [FD eye]/P(in) [untreated control]), increased significantly 45 days after FD was induced (P<0.05). In FD myopia in tree shrews, the BRB permeability increases abnormally. Impaired BRB function might be a secondary effect of myopia development rather than the cause of myopia.