Makoto Araie

Refractive Errors in an Elderly Japanese Population: The Tajimi Study

PURPOSE To evaluate the prevalence of refractive errors associated with age, gender, and central corneal thickness and to evaluate astigmatism in the refraction and keratometry in a randomly sampled elderly Japanese population. DESIGN Population-based epidemiologic survey. PARTICIPANTS A random sampling of residents of Tajimi, Japan, aged 40 years or older. A total of 3021 residents (participation rate, 78.1%) participated. METHODS Each subject underwent screening examinations including autokeratorefractometry, subjective refraction, best-corrected visual acuity, central corneal thickness measurement, intraocular pressure measurement, slit-lamp examination, fundus photography, and visual field testing. MAIN OUTCOME MEASURES The prevalence of myopia (spherical equivalent [SE], <-0.5 diopters [D]), high myopia (SE, <-5 D), hyperopia (SE, >0.5 D), refractive astigmatism (cylinder, >0.5 D), and anisometropia (difference in SE between eyes, >1.0 D), and the correlation of refractive errors with age, gender, and central corneal thickness. Astigmatism in the refraction and keratometry was analyzed using polar value analysis and the vector calculation method. RESULTS The crude prevalence of myopia, high myopia, hyperopia, refractive astigmatism in the refraction, and anisometropia was 41.8% (95% confidence interval [CI], 40.0%-43.6%), 8.2% (95% CI, 7.2%-9.2%), 27.9% (95% CI, 26.3%-29.6%), 54.0% (95% CI, 52.1%-55.8%), and 15.1% (95% CI, 13.7%-16.4%), respectively. The prevalence of myopia decreased with age up to 70 to 79 years but increased slightly in patients 80 years and older; the prevalence of hyperopia showed the opposite trend. The prevalence of astigmatism and anisometropia was higher in the older age groups. No significant gender difference was found associated with the refractive status except for keratometric readings. Polar value analysis and the vector calculation method showed a trend toward against-the-rule astigmatism with increasing age in both refractive and keratometric astigmatism, with a discrepancy between the two. CONCLUSIONS The overall prevalence of myopia (SE, <-0.5 diopters) was 41.8% in the study population, which is higher than that in population-based studies previously reported.

Use of laser speckle flowgraphy in ocular blood flow research

Acta Ophthalmol. 2010: 88: 723–729

Non-contact, two-dimensional measurement of tissue circulation in choroid and optic nerve head using laser speckle phenomenon

A new apparatus has been developed using the laser speckle phenomenon for non-contact, two-dimensional analysis of tissue circulation in the choroid and optic nerve head (ONH). The fundus was illuminated by a diode laser spot and its image speckle was detected by an image sensor. The difference between the average of the speckle intensity (Imean) and the speckle intensity for successive scannings was calculated, and the ratio of Imean to this difference was defined as normalized blur (NB), which is a quantitative index of blood velocity. The results were displayed on color graphic monitors showing the two-dimensional variation of the NB level in the measurement field. In the rabbit, this apparatus was used to study the relationship between the results of NB measurement and the choroidal blood flow determined by the microsphere technique, the relationship between NB obtained from the ONH tissue free of visible surface vessels and the ocular perfusion pressure (OPP) after a lethal injection of pentobarital, and the effect of intraocular pressure (IOP) on the NB in the choroid or in the ONH. A stepwise reduction in the OPP was introduced by elevating the IOP manometrically. The relative decrease in the average NB over the field measured, NBav, in the choroid with the reduction in OPP showed a significant correlation with the relative change in the blood flow rate determined using the microsphere technique (r = 0.60, P < 0.001). NBav in the ONH had a good correlation with the OPP after a lethal injection of pentobarbital (r = 0.98, P < 0.001). NBav in the choroid decreased with reduction in the OPP. Although NBav in the ONH was little affected by OPP change when OPP was above 40 mmHg, at OPP levels below 40 mmHg, NBav in the ONH decreased along with a reduction in the OPP. These results suggest that by using the present apparatus, the blood velocity in the choroid or ONH under various conditions can be studied non-invasively in the living eye.

Factors Contributing to the Progression of Visual Field Damage in Eyes with Normaltension Glaucoma

PURPOSE To evaluate the contribution of various factors on the progression of visual field damage in normal-tension glaucoma. METHODS Follow-up data of 56 eyes of 56 patients with normal-tension glaucoma, all of whom had an early stage of the disease with a mean deviation of -5 decibels or greater and were followed without therapy, were analyzed using regression analysis of survival data based on the Cox proportional hazards model. Factors studied were age, sex, presence or absence of diabetes or family history of glaucoma, refraction, systolic and diastolic pressures, cup:disc ratio, ratio of area of parapapillary atrophy to disc area, the mean deviations of the studied and contralateral eyes, and intraocular pressure and occurrence of disc bleeding during follow-up, both of which were treated as time-dependent variables. The progression of visual field damage was based on the glaucoma change probability analysis. RESULTS Cup:disc ratio, ratio of area of parapapillary atrophy to disc area, and intraocular pressure were found to have significant influence on the progression of visual field damage in normal-tension glaucoma. CONCLUSION Intraocular pressure may be involved in the development of normal-tension glaucoma. However, further prospective studies are needed to determine the validity of such a conclusion.

Automated layer segmentation of macular OCT images using dual-scale gradient information

A novel automated boundary segmentation algorithm is proposed for fast and reliable quantification of nine intra-retinal boundaries in optical coherence tomography (OCT) images. The algorithm employs a two-step segmentation schema based on gradient information in dual scales, utilizing local and complementary global gradient information simultaneously. A shortest path search is applied to optimize the edge selection. The segmentation algorithm was validated with independent manual segmentation and a reproducibility study. It demonstrates high accuracy and reproducibility in segmenting normal 3D OCT volumes. The execution time is about 16 seconds per volume (480x512x128 voxels). The algorithm shows potential for quantifying images from diseased retinas as well.

Neurotrophic function of conditioned medium from human amniotic epithelial cells.

Human amniotic epithelial cells (HAEC) may have pluripotent function because they are formed from the epiblast cells at the 8th day of fertilization. Previously, we reported that HAEC have the capacity to synthesize and release acetylcholine and catecholamine associated with the binding sites of catecholamine receptors. We show the neurotrophic function of a conditioned medium from HAEC using cultured cortical neurons of E18 rats. Extensive analyses with various techniques demonstrated that HAEC and immortalized HAEC synthesize and release brain‐derived neurotrophic factor (BDNF), neurotrophin‐3 (NT‐3) and nerve growth factor (NGF). Other neurotrophic factors were not detected in a cultured medium of HAEC by enzyme immunoassay. Various neurotrophic factors or growth factors did not show neurotrophic effects on E18 rat neuron except for EGF. Because EGF was not detected in the conditioned medium of HAEC, these data indicate an unidentified neurotrophic factor presently that is synthesized and released from HAEC. The amniotic membrane may have a significant role in supplying neurotrophic factors to the amniotic fluid as well as neurotransmitters, suggesting an important function to the early stages of neural development in the embryo. J. Neurosci. Res. 62:585–590, 2000.

Corneal thickness measurements: scanning-slit corneal topography and noncontact specular microscopy versus ultrasonic pachymetry ☆

Purpose: To compare central corneal thickness measurements taken with 3 pachymetry systems: Orbscan scanning‐slit corneal topography/pachymetry, Topcon SP2000P noncontact specular microscopy, and Tomey ultrasonic pachymetry. Setting: Multicenter study, Tokyo, Japan. Methods: In 216 healthy eyes of 114 subjects, scanning‐slit topography, noncontact specular microscopy, and ultrasonic pachymetry were used in that sequence to record central corneal thickness. In another 20 healthy eyes of 13 subjects, 2 sets of measurements were repeated for each pachymetry to assess repeatability. Results: The mean central corneal thickness was compatible between scanning‐slit topography (546.9 &mgr;m ± 35.4 [SD]) and ultrasonic pachymetry (548.1 ± 33.0 &mgr;m); however, noncontact specular microscopy gave a significantly smaller mean (525.3 ± 31.4 &mgr;m) than the other 2 tests (P<.001, Tukey multiple comparison). There were significant linear correlations between scanning‐slit topography and noncontact specular microscopy (r = 0.846, P<.001), noncontact specular microscopy and ultrasonic pachymetry (r = 0.897, P<.001), and ultrasonic pachymetry and scanning‐slit topography (r = 0.852, P<.001). Noncontact specular microscopy tended to show the best repeatability; however, the difference was not statistically significant (P = .663, repeated‐measure analysis of variance). Conclusions: Corneal thickness readings were comparable between scanning‐slit topography and pachymetry; noncontact specular microscopy gave significantly smaller values. The measurements of the 3 methods showed significant linear correlations with one another. All methods provided acceptable repeatability of measurements.

Intraocular pressure-lowering effects and safety of topical administration of a selective ROCK inhibitor, SNJ-1656, in healthy volunteers.

OBJECTIVE To investigate the effects and safety of topical administration of an ophthalmic solution of a selective Rho-associated coiled coil-forming protein kinase (ROCK) inhibitor, SNJ-1656, 0.003% to 0.1%, in healthy male adult volunteers. DESIGN Randomized, double-masked, group-comparison, phase 1 clinical study. In the initial single-instillation trial, 45 healthy volunteers were randomly subdivided into 5 groups and treated with SNJ-1656 in concentrations of 0.003%, 0.01%, 0.03%, 0.05%, and 0.1% in stepwise fashion. In the repeated-instillation trial, 36 healthy volunteers were assigned to receive SNJ-1656 ophthalmic solution at the following concentrations and dosages: 0.05% once daily, 0.1% once daily, 0.05% twice daily, or 0.1% twice daily. In our studies, the administration of the solution and subsequent examinations (including intraocular pressure [IOP] measurements) were performed in a double-masked fashion. RESULTS After single instillation of placebo or SNJ-1656, in concentrations of 0.003%, 0.01%, 0.03%, 0.05%, and 0.1%, the changes in IOP from the baseline were -0.91, -1.18, -1.48, - 2.20 (P = .04 vs placebo), -1.48, and -1.98 mm Hg, respectively, at 2 hours, and -0.63,-0.95, -1.79, -2.26 (P = .01 vs placebo), -1.95, and -3.00 mm Hg (P < .001 vs placebo) respectively, at 4 hours. Significant IOP reductions after repeated instillation were also found. On slitlamp examination during the trial, there were no significant adverse findings except hyperemia of the bulbar and palpebral conjunctiva after instillation. CONCLUSION This clinical study demonstrated that SNJ-1656 is a safe topical agent effective in reducing IOP in human eyes.

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.

Variation in optic nerve and macular structure with age and race with spectral-domain optical coherence tomography.

PURPOSE To evaluate the effects of age and race on optic disc, retinal nerve fiber layer (RNFL), and macular measurements with spectral-domain optical coherence tomography (SD OCT). DESIGN Cross-sectional observational study. PARTICIPANTS Three hundred fifty adult subjects without ocular disease. METHODS Data from SD OCT imaging of the optic nerve head, peripapillary RNFL, and macula of 632 eyes from 350 subjects without ocular disease were imaged with SD OCT. Multivariate models were used to determine the effect of age and race on quantitative measurements of optic disc, RNFL, and macula. MAIN OUTCOME MEASURES Optic nerve, RNFL, and macular measurements with SD OCT across racial strata and age. RESULTS For optic nerve parameters, participants of European descent had significantly smaller optic disc area than other groups (P<0.0001), and Indian participants had significantly smaller rim area than other groups (P<0.0001). Indian and Hispanic participants had thicker global RNFL measurements than other groups (P<0.0001). Participants of African descent were associated with thinner inner retinal thickness in the macula (P<0.0001). Age was associated with several parameters, with rim area reducing by 0.005 mm(2)/year, RNFL thickness reducing by 0.18 μm/year, and inner retinal thickness reducing by 0.1 μm/year (P<0.0001 for all age associations). CONCLUSIONS Optic nerve, RNFL, and macular measurements with SD OCT all varied across racial groups and with age. These differences are important in defining the range of normal variation in differing populations and should be considered in the use of these instruments in the detection of optic nerve and macular disease across these population groups. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.