Aiko Iwase

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.

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.

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.

Ocular and systemic factors related to intraocular pressure in Japanese adults: the Tajimi study

Background: As intraocular pressure (IOP) and age are consistent risk factors of glaucoma, it is of special interest to know the association between IOP and possibly relating factors including age in Japan where a high prevalence of normal-tension glaucoma has been reported. The aim of this report was to evaluate the distribution of and factors related to applanation IOP in a population-based study in Japan. Methods: A randomly sampled group of 3021 residents (response rate 78.1%) of Tajimi City, aged 40 years or older, underwent screening examinations including measurements of IOP with Goldmann applanation tonometry and central corneal thickness. Results: Among right eyes without glaucoma, suspected glaucoma or other disorders which could affect correct IOP measurements, IOP averaged 14.6 (SD 2.7) and 14.5 (2.5) mm Hg in men and women, respectively, with no significant intergender difference (p = 0.342). Multiple regression analyses revealed that age was significantly negatively correlated with IOP (non-standardised beta (B) = −0.020/year, p = 0.0001). Higher body mass index (B = 0.14/BMI, p<0.0001), higher mean blood pressure (B = 0.022/mm Hg, p<0.0001), history of diabetes (p = 0.0019), thicker cornea (B = 0.014/μm, p<0.0001), higher myopia (B = 0.055/dioptres, p = 0.0043) and steeper corneal curvature (B = −0.72/mm, p = 0.0002) were also significantly correlated with higher IOP. Conclusions: In an adult Japanese population, applanation IOP averaged 14.5 mm Hg and was negatively correlated with age after adjusting for other related factors. A positive correlation between IOP and myopia was found.

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.

Localized wedge-shaped defects of retinal nerve fiber layer and disc hemorrhage in glaucoma.

OBJECTIVE To evaluate frequencies of localized wedge-shaped defects of the retinal nerve fiber layer (RNFL) in eyes with and without disc hemorrhage in normal-tension glaucoma (NTG) and primary open-angle glaucoma (POAG). This study also aims to define a topographic correlation between disc hemorrhage and localized RNFL defects in POAG. DESIGN Cross-sectional study. PARTICIPANTS AND CONTROLS The authors studied 83 eyes of 83 patients with NTG (male/female = 23/60; age, 58.8+/-12.9 years) and 20 eyes of 20 patients with POAG (male/female = 9/11; age, 61.6+/-11.4 years); subjects in both groups had developed new disc hemorrhage at the time of enrollment. The authors randomly selected 45 eyes of 45 patients with NTG (male/female = 20/25; age, 62.0+/-9.3 years) and 24 eyes of 24 patients with POAG (male/female = 13/11; age, 56.3+/-14.5 years) with no history of disc hemorrhage during the follow-up period of more than 2 years. METHODS Visual field in the patients with POAG was matched to that of the patients with NTG regarding global indices for both the hemorrhage and the nonhemorrhage groups. Localized wedge-shaped defects of RNFL were identified by scanning laser ophthalmoscopy using an argon-blue laser. MAIN OUTCOME MEASURES The frequency of localized RNFL defects and the relationship between the locations of disc hemorrhages and localized RNFL defects were determined. RESULTS Localized wedge-shaped defects of RNFL occurred significantly more often in the hemorrhage group than in the nonhemorrhage group in both NTG (Fishers exact probability test, P < 0.0001) and POAG (P < 0.05) patients. Regardless of the presence of disc hemorrhage, there was no significant difference in the frequency of localized RNFL defects between patients with NTG and those with POAG. Most disc hemorrhages were present in the vicinity of the border between localized RNFL defects and relatively healthy-looking RNFL in both patients with POAG and those with NTG. CONCLUSION Disc hemorrhage is associated with localized damage of RNFL in both NTG and POAG.

Frequency doubling technology and confocal scanning ophthalmoscopic optic disc analysis in open-angle glaucoma with hemifield defects.

PurposeTo evaluate the potential of frequency doubling technology for detecting early glaucomatous damage. Patients and MethodsForty-nine eyes of 49 patients with open-angle glaucoma with visual field defects only in one hemifield according to the Humphrey Field Analyzer 30–2 program were included. Forty-five healthy patients were also included as control subjects. In each patient, frequency doubling technology with the threshold N-30 program and optic disc analysis using the Heidelberg Retina Tomograph was performed. Frequency doubling technology test results and the Humphrey Field Analyzer test results were compared. Optic disc parameters corresponding to the hemifield designated intact by the Humphrey Field Analyzer were compared between the eyes in which the hemifield was normal by frequency doubling technology and those in which the hemifield was abnormal. ResultsForty-one percent of the 49 hemifields designated intact by the Humphrey Field Analyzer were abnormal based on frequency doubling technology, whereas 98% of the 49 hemifields designated defective by the Humphrey Field Analyzer were abnormal and 12% of the 90 hemifields designated intact by the Humphrey Field Analyzer were abnormal in healthy patients. The percentage of the hemifields designated abnormal by frequency doubling technology was significantly higher than that in healthy patients (P < 0.001). The rim volume was significantly smaller in eyes with abnormal results based on frequency doubling technology than in eyes with normal results (P < 0.05, paired t test, with Bonferroni correction for multiple comparison). ConclusionFrequency doubling technology can detect glaucomatous damage earlier than conventional static perimetry can.

Intraocular Pressure and Related Systemic and Ocular Biometric Factors in a Population-Based Study in Japan: The Kumejima Study

PURPOSE To examine the distribution of intraocular pressure (IOP) and its related systemic and ocular biometric factors in a population-based study in a southwestern island of Japan. DESIGN Cross-sectional, population-based study. METHODS All residents of Kumejima Island, Japan, located in southwestern Japan (eastern longitude, 126 degrees 48 minutes and northern latitude 26 degrees 20 minutes), 40 years of age and older were asked to undergo a comprehensive questionnaire and ocular examination, including measurement of IOP with Goldmann applanation tonometry. RESULTS Of the 4632 eligible residents, 3762 (81.2%) underwent the examination. In 2838 non-glaucomatous subjects from whom reliable measurements of IOP were obtained, the mean IOPs +/- standard deviation in all, men, and women were 15.1 +/- 3.1 mm Hg (n = 2838), 15.2 +/- 3.1 mm Hg (n = 1450), and 15.1 +/- 3.0 mm Hg (n = 1388), respectively, with no significant intersex difference (P = .63). Multivariate regression analysis demonstrated that higher IOP was significantly correlated with younger age (P < .001), higher body mass index (P < .001), higher systolic blood pressure (P < .001), history of diabetes mellitus (P = .001), thicker central corneal thickness (P < .001), steeper corneal curvature (P < .001), and longer axial length (P < .018), but not with anterior chamber depth and the Shaffer angle width grade. CONCLUSIONS Younger age, higher body mass index, higher systolic blood pressure, diabetes, thicker central corneal thickness, and steeper corneal curvature were significantly correlated with higher IOP. The present results confirm that IOP is associated with systemic and ocular biometric factors and may define specific subgroups most likely to have an elevated IOP.

Common Variants on Chromosome 9p21 Are Associated with Normal Tension Glaucoma

Although intraocular pressure (IOP) is the most definitive cause of glaucoma, a subtype of open angle glaucoma (OAG) termed normal tension glaucoma (NTG), which occurs in spite of normal IOP, accounts for a large part of glaucoma cases, especially in Japan. To find common genetic variants contributing to NTG in Japanese patients, we conducted a genome-wide association study (GWAS). We performed the first screening for 531,009 autosomal SNPs with a discovery cohort of 286 cases and 557 controls, and then a second screening for the top 30 suggestive loci in an independent cohort of 183 cases and 514 controls. Our findings identified a significantly associated SNP; rs523096 [combined p-value = 7.40× 10−8, odds ratio (OR)  = 2.00 with 95% confidence interval (CI) 1.55–2.58] located 10 kbp upstream of CDKN2B on chromosome 9p21. Moreover, analysis of another independent case-control set successfully replicated the results of the screening studies (combined values of all 3 stages p = 4.96 × 10−11, OR  = 2.13 with 95% CI 1.69–2.68). The SNPs near rs523096 were recently reported to be associated with OAG associated with elevated IOP in primary open-angle glaucoma (POAG), the predominant subtype of glaucoma in Caucasian populations. Our results revealed that the 9p21 locus is also associated with NTG in Japanese. In addition, we identified SNPs more strongly associated with NTG.