Taiichi Hikichi

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.

Features of abnormal choroidal circulation in central serous chorioretinopathy

Aims: To evaluate abnormalities in the choroidal circulation in cases of central serous chorioretinopathy (CSC). Methods: A complete clinical ophthalmological examination was performed using simultaneous fluorescein and indocyanine green (ICG) angiography with a confocal scanning laser ophthalmoscopy and the digital images analysed in 36 consecutive patients with acute CSC. To quantify the choroidal circulation, the foveal choroidal blood flow was measured in 11 patients using laser Doppler flowmetry. Results: Fluorescein angiography showed focal leakage from the retinal pigment epithelium in all patients. ICG angiography revealed delays in arterial filling in 27 eyes (75%), and fluorescein angiography showed small hypofluorescent points around the leakage in 27 eyes (75%). Abnormal choroidal hyperfluorescence was observed in 30 eyes (83%). The choroidal blood flow in eyes with CSC was 45% lower than in fellow eyes (p<0.01). Conclusion: Decreased choroidal blood flow in CSC was demonstrated for the first time. The decreased choroidal blood flow might be correlated with the small, localised hypofluorescent areas, which may indicate non-perfused areas of the choriocapillaris that are frequently seen during ICG angiography.

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.

Inhibitory effect of losartan on laser-induced choroidal neovascularization in rats

PURPOSE To investigate the inhibitory effects of losartan, an angiotensin receptor antagonist, on angiogenesis in a rat model of laser-induced choroidal neovascularization. METHODS Experimental study. Fifteen Brown-Norway male rats received losartan (approximately 5 mg/kg/d) in drinking water, and 15 Brown-Norway male rats received unsupplemented drinking water 1 week before photocoagulation, and it was continued to the end of the study. Two weeks after intense laser photocoagulation, choroidal neovascularization was evaluated by fluorescein angiography and histopathologic evaluation. RESULTS The incidence of choroidal neovascularization formation was 99.5 +/-.2% (mean +/- standard deviation) in controls and 72.5 +/- 8.8% in losartan-treated rats (P <.01). Quantitative morphometric assessment revealed mean choroidal neovascularization lesion thickness of 54 and 44.8 microm, respectively, in controls and losartan-treated rats (P <.01). CONCLUSION Losartan seems to inhibit development of laser-induced choroidal neovascularization. Angiotensin receptor antagonists may be useful as prophylaxis against choroidal neovascularization associated with age-related macular degeneration.

Association of preoperative photoreceptor displacement and improved central scotoma after idiopathic macular hole surgery

OBJECTIVE To investigate the relationship between preoperative photoreceptor displacement and postoperative scotoma after unilateral idiopathic macular hole surgery. DESIGN Prospective nonrandomized comparative self-controlled trial. PARTICIPANTS Twenty patients who underwent successful surgery for unilateral idiopathic macular hole participated in the study. METHODS Kinetic perimetry using red and green filter glasses, black binocular fixation targets, and red and green selective monocular stimuli was performed preoperatively. Scanning laser ophthalmoscope (SLO) microperimetry was performed preoperatively and postoperatively. RESULTS Sixteen patients had photoreceptor displacement preoperatively. In preoperative SLO microperimetry, all eyes with a macular hole had a scotoma; postoperatively, 12 of 16 had no scotoma. All four eyes with no preoperative photoreceptor displacement were noted to have a postoperative scotoma. The prevalence of postoperative scotoma in patients with preoperative photoreceptor displacement (4 of 16; 25%) was significantly lower than that in patients without preoperative photoreceptor displacement (4 of 4; 100%) (P = 0.03). CONCLUSIONS The presence or absence of photoreceptor displacement preoperatively should affect postsurgical visual function. Photoreceptor damage may occur in eyes without photoreceptor displacement preoperatively, resulting in scotoma postoperatively.

Abnormal vitreous structure in optic nerve pit

A 37-year-old man presented with an optic nerve pit and serous macular detachment of the left eye. Scanning laser ophthalmoscopy revealed a cyst-like structure terminating at the pit in the premacular vitreous. During ocular movement, this structure moved vigorously and seemed to exert traction on the pit. We believe that it is part of an anomalous Cloquets canal, and that traction on the pit may be a significant factor in the development of serous macular detachment in this patient.