Motohiro Shirakashi

Effects of Age, Sex, and Axial Length on the Three-Dimensional Profile of Normal Macular Layer Structures

PURPOSE To identify sex-related differences and age-related changes in individual retinal layer thicknesses in a population of healthy eyes across the lifespan, using spectral domain optical coherence tomography (SD-OCT). METHODS In seven institutes in Japan, mean thicknesses of the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptor inner segment (IS), and photoreceptor outer segment (OS) were measured using SD-OCT with a new automated segmentation protocol in 256 healthy subjects. RESULTS Interoperator coefficients of variability for measurements of each layer ranged from 0.012 to 0.038. The RNFL, GCL, IPL, and INL were thinnest in the foveal area, whereas the OPL+ONL and OS were thickest in this area. Mean thicknesses of the INL and the OPL+ONL were significantly greater in men (P = 0.002 and 0.001, respectively). However, mean RNFL thickness was greater in women (P = 0.006). Thicknesses of the RNFL, GCL, IPL, INL, and IS correlated negatively with age. Thickness of the OPL+ONL was not correlated with age, and thickness of the OS correlated positively with age. Inner retinal (RNFL+GCL+IPL) thickness over the whole macula correlated negatively with age (P < 0.001), but outer retinal (OPL+ONL+IS+OS) thickness did not. Thicknesses of layers did not correlate with axial length. CONCLUSIONS Macular layer thicknesses measured on SD-OCT images in healthy eyes showed significant variations by sex and age. These findings should inform macular layer thickness analyses in SD-OCT studies of retinal diseases and glaucoma.

Three-Dimensional Profile of Macular Retinal Thickness in Normal Japanese Eyes

PURPOSE To demonstrate the three-dimensional macular thickness distribution in normal subjects by spectral domain optical coherence tomography (SD-OCT) and evaluate its association with sex, age, and axial length. METHODS Mean regional retinal thickness measurements on the Early Treatment Diabetic Retinopathy Study (ETDRS) layout were obtained by three-dimensional raster scanning (6 x 6 mm) using SD-OCT in 248 normal eyes of 248 Japanese subjects. RESULTS Mean foveal thickness was 222 +/- 19 microm; it was significantly greater in men (226 +/- 19 microm) than in women (218 +/- 18 microm; P = 0.002) and did not correlate with age in either sex. Mean sectoral retinal thickness was also significantly greater in the men than in the women in all the quadrants of the inner ring (1-3 mm; P < 0.001 and P = 0.001-0.007) and in the temporal quadrant of the outer ring (3-6 mm; P < 0.001). The retinal thicknesses of each of the ETDRS sectors did not correlate significantly with axial length after adjustment for age in either sex. Retinal thickness in six of the eight sectors in the inner and outer rings showed a negative correlation with age after adjustment for axial length in the men (P < 0.001 and P = 0.001-0.018), whereas no correlation with age was observed in the women. CONCLUSIONS SD-OCT demonstrated the three-dimensional macular thickness distribution in normal eyes. Macular thickness varied significantly with sex and age. These variables should be considered while evaluating macular thickness.

Peripapillary Retinal Nerve Fiber Layer Thickness Determined by Spectral-Domain Optical Coherence Tomography in Ophthalmologically Normal Eyes

OBJECTIVES To evaluate the peripapillary distribution of retinal nerve fiber layer thickness (RNFLT) in normal eyes using spectral-domain optical coherence tomography and to study potentially related factors. METHODS In 7 institutes in Japan, RNFLT in 7 concentric peripapillary circles with diameters ranging from 2.2 to 4.0 mm were measured using spectral-domain optical coherence tomography in 251 ophthalmologically normal subjects. Multiple regression analysis for the association of RNFLT with sex, age, axial length, and disc area was performed. RESULTS Retinal nerve fiber layer thickness decreased linearly from 125 to 89 μm as the measurement diameter increased (P < .001, mixed linear model). Retinal nerve fiber layer thickness correlated with age in all diameters (partial correlation coefficient [PCC] = -0.40 to -0.32; P < .001) and negatively correlated with disc area in the 2 innermost circles but positively correlated in the 3 outermost circles (PCC = -0.30 to -0.22 and 0.17 to 0.20; P ≤ .005). Sex and axial length did not correlate with RNFLT (P > .08). The decay slope was smallest in the temporal and largest in the nasal and inferior quadrants (P < .001); positively correlated with disc area (PCC = 0.13 to 0.51; P ≤ .04); and negatively correlated with RNFLT (PCC = -0.51 to -0.15; P ≤ .01). CONCLUSIONS In normal Japanese eyes, RNFLT significantly correlated with age and disc area, but not with sex or axial length. Retinal nerve fiber layer thickness decreased linearly as the measurement diameter increased. The decay slope of RNFLT was steepest in the nasal and inferior quadrants and steeper in eyes with increased RNFLT or smaller optic discs.

Intraocular Pressure-Dependent Progression of Visual Field Loss in Advanced Primary Open-Angle Glaucoma: A 15-Year Follow-Up

We studied the relationship between intraocular pressure (IOP) and progression of visual filed loss in 83 eyes of 83 patients with advanced primary open-angle glaucoma (loss of at least one quarter of the visual field on Goldmann perimetry). During the 15-year follow-up study, 71 eyes (86%) showed progression of visual field loss. The mean IOP was significantly lower in eyes that remained stable (13.4 +/- 1.3 mm Hg) than in those that showed progression of visual field loss (19.4 +/- 2.6 mm Hg). These results suggest that it is necessary to reduce IOP to below 15 mm Hg to prevent further progression of visual filed loss in advanced glaucoma.

Measurement of microcirculation in the optic nerve head by laser speckle flowgraphy and scanning laser doppler flowmetry

PURPOSE To evaluate and compare blood flow measurements by laser speckle flowgraphy and scanning laser Doppler flowmetry in the optic nerve head of normal volunteers. METHODS This prospective study included 60 eyes of 60 normal volunteers (50.0 years; range, 21 to 77 years). Measurements were taken at the temporal neuroretinal rim away from visible vessels. The square blur rate, a quantitative index of relative blood velocity, was measured by laser speckle flowgraphy. Using scanning laser Doppler flowmetry, volume, flow, and velocity were measured at the same neuroretinal rim locations. RESULTS The average square blur rate, volume, flow, and velocity were 7.11 +/- 1.65, 7.74 +/- 3.19, 151.85 +/- 70.63, and 0.53 +/- 0. 23 arbitrary units, respectively (n = 60). Square blur rate correlated significantly with flow and velocity (r =.361, P =.005; r =.359, P =.005, respectively). However, there was no significant correlation between square blur rate and volume (r =.101, P =.441). Although square blur rate decreased significantly with increasing age (r = -.375, P =.003), volume, flow, or velocity showed no significant correlation with age (r = -.249, P =.054; r = -.166, P =. 205; r = -.143, P =.275, respectively). Square blur rate also decreased significantly with mean blood pressure (r = -.315, P =. 014), but volume, flow, or velocity showed no significant correlation with mean blood pressure (r = -.159, P =.225; r = -.059, P =.654; r = -.043, P =.742, respectively). CONCLUSION We found only a weak correlation between the blood flow indexes, as measured by laser speckle flowgraphy and scanning laser Doppler flowmetry because of basic differences in the principles of measurement.

Myopia and advanced-stage open-angle glaucoma

OBJECTIVE To investigate the effect of myopic refraction on the central visual field in patients with advanced open-angle glaucoma (OAG). DESIGN Multicenter cross-sectional study. PARTICIPANTS Three hundred thirteen OAG eyes (176 eyes of 176 primary open-angle glaucoma [POAG] patients and 137 eyes of 137 normal-tension glaucoma [NTG] patients) with clear ocular media and a mean deviation (MD) <-15 dB. Patients with a recorded maximum intraocular pressure (IOP) of 22 mmHg or greater were classified as POAG, and those with an IOP of 21 mmHg or less were classified as NTG. METHODS Multiple regression analysis was used to study the influence of refraction on 12 central test points of the C30-2 Humphrey program, and the differences in visual field defects between POAG and NTG eyes were examined using logistic discriminant analysis. In the multiple regression analysis, total deviation (TD) of the 12 test points was graded and used as the dependent variable, and MD and the spherical equivalent refraction were the explanatory variables. In the logistic discrimination analysis, TD, MD, and refraction were covariants that determined the OAG subtypes. MAIN OUTCOME MEASURES TD values of the 12 central test points (C30-2 program). RESULTS Higher myopic refraction was significantly associated with more damage at a point just temporal and inferior to the fixation point in POAG eyes, whereas it was significantly associated with less damage at test points just temporal and superior to the fixation point in NTG eyes. After correcting for the influence of refraction, POAG eyes had significantly more damage at a test point just temporal and inferior to the fixation point, whereas NTG eyes had significantly more damage at those test points nasal and inferior to the fixation point. CONCLUSIONS High myopia constitutes a threat to the remaining lower cecocentral visual field and is one of the factors that interfere with the quality of vision in advanced OAG with high IOP but not low IOP.

Prevalence of migraine in low-tension glaucoma and primary open-angle glaucoma in Japanese.

We studied the prevalence of migraine in low-tension glaucoma (LTG) and primary open-angle glaucoma (POAG). Seventy seven Japanese patients with LTG, 73 with POAG, and 75 normal subjects were randomly selected and tested with a headache questionnaire. The prevalence of headache with or without typical migrainous features (unilateral headache or ocular pain, nausea, vomiting, and visual disturbance before headache) was 51% in LTG, 42% in POAG, and 44% in normal patients. The prevalence of headache with two migrainous features or more (probable migraine) was 17% in LTG, 11% in POAG, and 12% in normal subjects. The prevalence of headache with three migrainous features (classical migraine) was 5% in LTG, 3% in POAG, and 3% in normal subjects. There was no statistically significant difference in the prevalence of any types of migraine between the three groups of patients (p greater than 0.05). These results suggest there is no significant relationship between migraine and LTG or POAG in Japanese patients.

Relation between size of optic disc and thickness of retinal nerve fibre layer in normal subjects

AIMS To evaluate the relation between the optic disc size and the thickness of the peripapillary retinal nerve fibre layer (RNFL) in normal Japanese subjects by means of scanning laser polarimetry. METHODS Scanning laser polarimetry was performed in 60 normal subjects. One eye of each subject was randomly selected for study. Using a scanning laser polarimeter, the integral of RNFL thickness was measured totally and regionally within a circular band located 1.75 disc diameters from the centre of the optic disc. The correlation between the optic disc size and the integral of RNFL thickness was examined. RESULTS The optic disc size showed a significant correlation with the integral of RNFL thickness (R = 0.497, p <0.001). A significant negative correlation was observed between the optic disc size and the ratio of inferior integral to total integral of RNFL thickness (R = −0.274, p = 0.034). CONCLUSIONS The cross sectional area occupied by the RNF, measured by scanning laser polarimetry increased significantly with an increase in optic disc size while the ratio of inferior to total cross sectional area decreased significantly. These facts should be considered when one evaluates the RNFL thickness in patients with progressive optic neuropathies such as glaucoma.

Measurement of microcirculation in optic nerve head by laser speckle flowgraphy in normal volunteers

PURPOSE To report blood flow in the optic nerve head between the right and left eyes or the superior and inferior neuroretinal rims in normal volunteers using laser speckle flowgraphy. METHODS This prospective study included 120 eyes of 60 normal volunteers (mean age, 50.0 +/- 16.9 years; range, 21 to 77 years). The square blur rate was measured by laser speckle flowgraphy (Kyushu Institute of Technology, Iizuka, Japan). The sequence of eye measurements was randomized. In each eye, measurements were taken at the neuroretinal rim away from visible vessels. Linear regression analysis, paired two-tailed t test, and two-way analysis of variance were used for statistical analysis. P values less than.05 were accepted as statistically significant. RESULTS There was a significant correlation in square blur rate between the right and left eyes (r = 0.587, P <.001). Square blur rate in the superior temporal neuroretinal rim significantly correlated with that in the inferior temporal neuroretinal rim in each of the right (r = 0.546, P <.001) and left (r = 0.465, P <.001) eyes. Square blur rate in the right eye was higher than that in the left eye (P =.049). Square blur rate in the superior neuroretinal rim was higher than that in the inferior neuroretinal rim in both the right (P =.035) and left (P =. 005) eyes. CONCLUSION There were statistically significant differences of optic nerve head blood flow in normal volunteers using laser speckle flowgraphy between the right and left eyes and between the superior and inferior temporal neuroretinal rims. These normal data can be used for understanding physiological ocular hemodynamics.

Laser Scanning Tomography of Optic Discs of the Normal Japanese Population in a Population-based Setting

OBJECTIVE To evaluate the optic disc characteristics using the Heidelberg retina tomograph (HRT) II in a large sample of normal Japanese subjects. DESIGN Cross-sectional study. PARTICIPANTS A total of 3576 eyes of 2036 normal subjects, with good-quality HRT II images, of 6042 eyes of 3021 subjects aged 40 years or more who participated in the Tajimi Study, a population-based eye study in Japan. METHODS Optic disc parameters were obtained using HRT II, and the association of gender, age, height, weight, blood pressure, ocular perfusion pressure, refraction, intraocular pressure (IOP), central corneal thickness (CCT), and disc size on HRT parameters was assessed using simple and multiple regression analyses. MAIN OUTCOME MEASURES HRT parameters, including disc area, cup area, rim area, cup-to-disc area ratio, cup volume, rim volume, mean cup depth, maximum cup depth, height variation contour, cup shape measure, mean retinal nerve fiber layer (RNFL) thickness, and RNFL cross-sectional area, and the crude and partial correlations of the potential confounders with the HRT parameters. RESULTS Disc area, cup-to-disc area ratio, and rim area averaged 2.06+/-0.41 mm(2) (mean+/-standard deviation), 0.23+/-0.13, and 1.55+/-0.29 mm(2), respectively. All HRT parameters were strongly or moderately correlated between right and left eyes (Pearsons correlation coefficients = 0.45-0.83, P<0.001). Absolute inter-eye differences in several HRT parameters were positively correlated with disc area (P<0.05). Multiple regression analyses adjusting for the confounders showed weak but significant correlations of height, refractive error, IOP, and CCT with several HRT parameters (partial correlation coefficient (absolute value) = 0.04-0.16, P<0.05), and moderate or weak but significant correlations of disc area with all HRT parameters (partial correlation coefficient [absolute value] = 0.05-0.73, P<0.05). Gender, weight, blood pressure, and ocular perfusion pressure did not significantly correlate with HRT parameters. CONCLUSIONS This report presents reference data of normality for the HRT parameters based on a large sample of normal Japanese subjects. There were small but significant influences of height, refractive error, IOP, and CCT on several HRT parameters. Many HRT parameters were moderately or weakly affected by disc size. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.