Hitomi Saito

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.

Cross-sectional Anatomic Configurations of Peripapillary Atrophy Evaluated with Spectral Domain-Optical Coherence Tomography

PURPOSE To evaluate the cross-sectional configurations of peripapillary atrophy (PPA)-alpha and -beta in ophthalmologically normal subjects using spectral domain-optical coherence tomography (SD-OCT). METHODS One hundred twenty normal subjects had a complete ophthalmic examination including axial length measurement, standard automated perimetry, fundus imaging with photography, and SD-OCT (3D OCT-1000; Topcon Inc., Tokyo, Japan). PPA-alpha and -beta were identified in color photographs of the optic disc. Cross-sectional B-mode images of the peripapillary retina and sclera, including PPA-alpha and -beta obtained with SD-OCT, were analyzed. RESULTS Of 120 normal eyes, 120 (100%) had PPA-alpha and 90 (75%) had PPA-beta. In OCT images of the peripapillary retina, the ganglion cell layer and the inner and outer plexiform layers were observed to end in a tapering fashion at the edge of the optic disc, whereas the retinal nerve fiber layer continued into the optic cup. The external limiting membrane (ELM), inner-outer segments (IS-OS), and retinal pigment epithelium(RPE)/Bruchs membrane complex were significantly more commonly absent before the optic disc edge within the PPA-beta compared with areas outside the PPA-beta (P < 0.0001). Specific findings in the peripapillary area including slope and step configurations of the scleral bed and hump- and wedge-shaped appearances of the RPE-Bruchs membrane complex were identified in 63 (52.5%), 6 (5.0%), 19 (15.8%), and 6 (5.0%) of 120 eyes, respectively. The presence of the step configuration was associated with myopia and longer axial length (P = 0.0014 and 0.0105, respectively). CONCLUSIONS The cross-sectional anatomic configurations of the peripapillary atrophy were evaluated by using SD-OCT. The termination of the retinal layers and configurations of the scleral bed in the peripapillary area varied among normal subjects.

Spectral-Domain Optical Coherence Tomography ofβ-zone Peripapillary Atrophy: Influence of Myopiaand Glaucoma

PURPOSE To investigate the influence of glaucoma and myopia on the cross-sectional configuration of the β-zone of peripapillary atrophy (PPA-β) using spectral-domain optical coherence tomography (SD-OCT). METHODS Cross-sectional B-scan images of PPA-β obtained with SD-OCT were evaluated in 100 eyes of 100 consecutive patients with POAG, regardless of intraocular pressure level, and in 100 eyes of 100 normal subjects. PPA bed configurations were classified, and associated factors were studied with multivariate analysis. RESULTS In 147 eyes with PPA-β (84 POAG and 63 normal eyes; P = 0.0012), the PPA bed was composed of straight (14 POAG and 27 normal eyes) or downward-curved (19 and 8 eyes) Bruchs membrane (BM) or of a downward-bending slope lacking BM (BM defect; 51 and 28 eyes). Multivariate analysis revealed that absence of POAG (odds ratio [OR], 0.36; P = 0.034) and less myopic refractive error (OR, 1.43; P = 0.009) were significantly associated with straight-BM-type, presence of POAG (OR, 5.74; P = 0.008) and less myopic refractive error (OR, 3.02; P < 0.001) with curved-BM-type, and myopic refractive error (OR, 0.34; P < 0.001) with BM-defect-type. Within the PPA-β region, all retinal layers except for the nerve fiber layer frequently disappeared before reaching the disc edge, showing no significant intergroup difference (P > 0.05) between POAG and normal eyes. CONCLUSIONS PPA bed configurations detected by SD-OCT were classified into three types. The lack of BM on the PPA bed was closely associated with myopia. The downward-curved appearance of BM may be related to the anatomic changes associated with glaucoma.

Optic Disc and Peripapillary Morphology in Unilateral Nonarteritic Anterior Ischemic Optic Neuropathy and Age-and Refraction-Matched Normals

PURPOSE To compare optic disc morphologic features and peripapillary retinal nerve fiber layer (RNFL) thickness between the unaffected eyes of patients with unilateral nonarteritic anterior ischemic optic neuropathy (NAION) and their affected eyes and the eyes of age- and refraction-matched normal control subjects. DESIGN Cross-sectional comparative study. PARTICIPANTS Thirty-one patients with unilateral NAION and 62 age- and refraction-matched normal control subjects. METHODS Optic disc morphologic features and peripapillary RNFL thickness were evaluated in both eyes of patients with unilateral NAION and in one randomly chosen eye of the normal control subjects. MAIN OUTCOME MEASURES Optic disc and cup parameters were measured using the Heidelberg Retina Tomograph II (Heidelberg Engineering GmbH, Dossenheim, Germany), and RNFL thickness was measured by scanning laser polarimetry with variable corneal compensation (GDx VCC; Carl Zeiss Meditec, Dublin, CA). RESULTS There was no significant difference in the disc area between the NAION affected eyes and the unaffected fellow eyes. The cup area, cup-to-disc area ratio, cup volume, and cup shape measure were greater, whereas the peripapillary RNFL thickness was smaller in the former than the latter (P = 0.001 to approximately 0.043). When the unaffected eyes of patients with NAION and the age- and refraction-matched normal control eyes were compared, the disc area, cup area, cup-to-disc area ratio, cup volume, mean cup depth, and cup shape measure were smaller in the former (P = 0.0006 to approximately 0.03); there was no significant difference in the RNFL thickness between the two (P>0.06). CONCLUSIONS A comparison of the eyes with NAION and the fellow eyes indicated that the cup was slightly larger in the former than in the latter, suggesting the acquired enlargement of the cupping after NAION develops. A comparison of the unaffected fellow eyes in patients with NAION and the age- and refraction-matched normal control eyes suggested that a smaller disc area and smaller cupping were predisposing risk factors for the development of NAION.

Reproducibility of thickness measurements of macular inner retinal layers using SD-OCT with or without correction of ocular rotation.

PURPOSE To evaluate the intervisit reproducibility of spectral-domain optical coherence tomography (SD-OCT) measurement of the macular retinal nerve fiber layer thickness (mRNFLT); combined ganglion cell layer and inner plexiform layer (GCL+IPL) thickness; and ganglion cell complex (GCC) thicknesses (sum of mRNFLT and GCL+IPL thicknesses) compared with that of circumpapillary RNFLT (cpRNFLT) and the effect of ocular rotation on reproducibility. METHODS SD-OCT imaging was performed twice on different days in one eye of 58 normal subjects and 73 glaucoma patients. The reproducibility was evaluated for the entire 4.8-mm × 4.8-mm macular area and subareas (upper and lower halves, 2 × 2, 4 × 4, and 8 × 8 grids), and the 360°, upper, and lower halves mean cpRNFLT with and without correction of ocular rotation. RESULTS The coefficients of variation (CVs) of GCL+IPL and GCC thickness measurements averaged below 1.0% for the entire and upper and lower half macular areas, and below 4.2% in the macular subareas in normal and glaucoma eyes, which were significantly smaller (P < 0.001) than those of mRNFLT measurements in the same areas of the same eyes. The CVs of mRNFLT measurements were significantly smaller than those of the cpRNFLT only in the lower half mean area in normal eyes. The reproducibility was minimally affected by correction of ocular rotation or presence of glaucoma. CONCLUSIONS The reproducibility of the macular (GCL+IPL) and GCC thickness measurements was better than that of mRFNLT and cpRNFLT in normal and glaucoma eyes and minimally affected by correction of ocular rotation.

Sensitivity and Specificity of the Heidelberg Retina Tomograph II Version 3.0 in a Population-based Study: The Tajimi Study

PURPOSE To evaluate the sensitivity and specificity of the 3 glaucoma classification programs, the FS Mikelberg discriminant function (FSM), Moorfields Regression Analysis (MRA), and Glaucoma Probability Score (GPS) of version 3.0 of the Heidelberg Retina Tomograph (HRT) II (Heidelberg Engineering, Dossenheim, Germany), in a population-based setting for the first time. DESIGN Population-based cross-sectional study. PARTICIPANTS One randomly chosen eye of each subject without glaucoma, subject with glaucoma, and subject with suspected glaucoma with reliable HRT II measurements from the Tajimi study (2297 eyes of 2297 subjects) were included for analysis. METHODS Glaucoma was diagnosed by the optic disc and visual field findings according to the criteria of the International Society of Geographical and Epidemiological Ophthalmology. The sensitivity and specificity of FSM, MRA, and GPS were calculated. Characteristics of erroneously diagnosed glaucoma (false-negative) eyes and factors that influenced specificity with the 3 programs were investigated. MAIN OUTCOME MEASURES Sensitivity and specificity of FSM, MRA, and GPS. RESULTS Sensitivity and specificity varied significantly among the 3 programs: 59.1%, 39.4%, and 65.2% (P = 0.02 approximately 0.003, chi-square test), and 86.7%, 96.1%, and 83.0% (P<0.0001) with FMS, MRA, and GPS, respectively. MRA gave the lowest sensitivity but the highest specificity. Positive predictive values for these programs ranged between 0.10 and 0.23, whereas negative predictive values ranged between 0.98 and 0.99. False-negative eyes had significantly better visual field indexes (P<0.01 approximately 0.002, Mann-Whitney U test) and smaller cup and larger rim parameters compared with true-positive glaucoma eyes. Older age and hyperopia were negatively correlated with the specificity of GPS but not with that of FMS and MRA. Larger disc area was significantly associated with decreased specificity of all programs. CONCLUSIONS In a population-based setting, the sensitivity of the HRT II was unsatisfactory with any of the classification programs, whereas specificity was satisfactory. A significant percentage of the glaucoma discs were labeled as normal, and eyes in the earlier stage of the disease appear to be more likely to be misdiagnosed as normal. Factors such as age, refraction, and disc area had an influence on specificity, but the degree of its influence was different for each classification program.

Intraocular Pressure Change Over a Habitual 24-Hour Period After Changing Posture or Drinking Water and Related Factors in Normal Tension Glaucoma

PURPOSE We investigated the correlation between 24-hour IOP in the habitual (sitting during day and supine during night) position (H24h-IOP) and IOP after a postural-change test (PCT-IOP) and a water-drinking test (WDT-IOP). We also investigated ocular and systemic factors related with them in patients with normal tension glaucoma (NTG). METHODS Japanese NTG patients underwent H24h-IOP, PCT-IOP, and WDT-IOP measurements during a 24-hour period. Correlations among H24h-IOP, PCT-IOP, and WDT-IOP, and contributing ocular/systemic factors were investigated using regression analysis. RESULTS There were 33 patients included. Peak H24h-IOP correlated positively with peak PCT-IOP and peak WDT-IOP (estimate = 0.422 and 0.419, P ≤ 0.010), and peak PCT-IOP with WDT-IOP (0.44, P = 0.002). Peak H24h-IOP correlated with refraction (0.36, P = 0.048) and negatively with the mean deviation (MD, -0.066, P = 0.031). MD and baseline IOP (the mean of H24h-IOP) correlated negatively with the H24h-IOP fluctuation (-0.058 and -0.58, P ≤ 0.050). Refraction, baseline IOP, mean blood pressure (mBP), and body mass index (BMI) correlated with peak PCT-IOP (0.23, 0.52, 0.097, and 0.32, respectively, P ≤ 0.038). PCT-IOP difference correlated with refraction and mBP (0.31 and 0.093, P ≤ 0.016) and negatively with age (-0.069, P = 0.003). Central corneal thickness, baseline IOP, age, and BMI correlated with peak WDT-IOP (0.030, 0.40, 0.088, and 0.26, P ≤ 0.050). Age and BMI correlated with WDT-IOP difference (0.086 and 0.20, P < 0.032). CONCLUSIONS Positive correlation was found among the peaks of H24h-, PCT-, and WDT-IOP. A worse visual field was associated with higher peak and greater fluctuation of H24h-IOP in NTG. Several ocular/systemic factors were important in interpreting H24h-, PCT-, and WDT-IOP.

Confocal scanning laser ophthalmoscopy in high myopic eyes in a population-based setting.

PURPOSE To compare the parameters of confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph [HRT] II; Heidelberg Engineering, Heidelberg, Germany) in high myopia with those in age-matched emmetropia. METHODS A population-based study in which HRT II data were analyzed from 135 healthy subjects with high myopia (spherical equivalent [SE] from -6 to -12 D) and 135 age-matched subjects with emmetropia (SE from -1 to +1 D). The HRT parameters, the correlation between disc area and ovality, and asymmetry between the right and left eyes were evaluated. RESULTS High myopia was associated with greater disc ovality, smaller cup areas and cup volumes, higher rim volumes, height variation contour (HVC), and the mean retinal nerve fiber layer (RNFL) thickness compared with those parameters in emmetropia (P < or = 0.003). The intergroup differences in the rim volume and mean RNFL thickness remained significant (P = 0.003) after adjustment for the disc area and ovality. The disc area was correlated significantly (P < or = 0.002) with most parameters in both groups. The disc ovality was significantly (P = 0.005) negatively correlated with the disc area only in high myopia and significantly (P < or = 0.003) positively correlated with the rim volume, HVC, and mean RNFL thickness in both groups. Asymmetry of the mean RNFL thickness was significantly (P = 0.003) greater in high myopia than in emmetropia. CONCLUSIONS The characteristics of the HRT parameters in highly myopic eyes involved smaller cup parameters and greater rim and RNFL parameters compared with emmetropic eyes. The effects of disc area and ovality on the HRT parameters in highly myopic eyes differed from those in emmetropic eyes.