Hitomi Saito - Academia.edu (original) (raw)

Papers by Hitomi Saito

Research paper thumbnail of Structure-function Relationship In Macular Area Of Normal Eyes

Research paper thumbnail of Macular Thickness Analysis By SD-OCT In Glaucoma Eyes With Hemi-retinal Damage

Research paper thumbnail of Atypical retardation pattern in measurements of scanning laser polarimetry and its relating factors

Eye, Dec 12, 2008

Purpose To assess the prevalence of atypical retardation pattern (ARP) in scanning laser polarime... more Purpose To assess the prevalence of atypical retardation pattern (ARP) in scanning laser polarimetry (SLP) with variable corneal compensation (VCC) and enhanced corneal compensation (ECC), and to evaluate the factors relating to typical scan score (TSS). Methods Measurements of SLP-VCC, SLP-ECC, and the Humphrey field analyzer (HFA) were performed in 105 normal subjects and 82 open-angle glaucoma (OAG) patients. ARP was defined as an SLP image with TSSo80. Results Prevalence of ARP with SLP-VCC was 13.3 and 14.6% in normal and OAG eyes, respectively, and that with SLP-ECC (2.9% and 1.2%) was lower than SLP-VCC (Po0.009). TSS with SLP-VCC was significantly correlated with age (partial correlation coefficient (PCC) ¼ À0.22, P ¼ 0.003) and refractive error (PCC ¼ 0.26, Po0.001) after adjusting for each other. TSS with SLP-ECC was significantly correlated with neither age nor refractive error (PCC ¼ À0.02, P ¼ 0.788; PCC ¼ 0.10, P ¼ 0.177, respectively). In OAG eyes, mean deviation (MD) of HFA was significantly correlated with TSS with SLP-VCC and SLP-ECC (PCC ¼ 0.35, P ¼ 0.001; PCC ¼ 0.23, P ¼ 0.039, respectively). In SLP-VCC, MD was significantly correlated with retinal nerve fibrr layer (RNFL) thickness only after excluding eyes with ARP (Po0.001). Conclusions ARP in SLP-VCC measurements was found in more than 10% of normal or glaucomatous eyes, and TSS was significantly lower in older subjects, more myopic eyes, or eyes with more advanced glaucomatous damage. The presence of ARP disturbs the accuracy of RNFL thickness measurement by SLP-VCC. In SLP-ECC measurements, prevalence of ARP was considerably lower and TSS was not affected by age or refractive error, suggesting the advantages of ECC in clinical practices.

Research paper thumbnail of Performance of GDx VCC in eyes with peripapillary atrophy: comparison of three circle sizes

Eye, Aug 4, 2006

Purpose A scanning laser polarimetry (GDx VCC) equips three different sized measurement circles. ... more Purpose A scanning laser polarimetry (GDx VCC) equips three different sized measurement circles. In eyes with peripapillary atrophy (PPA), the GDx measurement becomes inaccurate when the circle falls on PPA. The aim of this study was to evaluate performance of the three circles of GDx measurement in eyes with PPA. Methods Three different sized circles were compared regarding frequency of PPA, which fell on each circle in 282 open-angle glaucoma (OAG) eyes, reproducibility of GDx parameters in 24 normal and 22 OAG eyes, and ability to detect glaucoma in 50 normal and 50 OAG eyes. Results PPA was observed in 230 (82%) of 282 OAG eyes. PPA fell on the small circle (default setting), medium, and large circles in 119 (43%), 38 (14%), and 12 (4%) of the 280 OAG eyes. Reproducibility of GDx parameters was not significantly different among three circles in normal eyes (P40.05), whereas coefficients of reproducibility of TSNIT average (P ¼ 0.006) and superior average (P ¼ 0.035) were smaller in the smaller circles in OAG eyes. GDx parameters significantly correlated (Po0.001), but were significantly different (Po0.05) between the small and medium circles. The area under receiver operating characteristic curves for dividing OAG from normal eyes using GDx parameters was similar between the small and medium circles. Conclusions If the medium circles were used, obstructing influences of PPA on GDx measurement could be avoided more often in Japanese OAG eyes with similar reproducibility and comparable ability to detect glaucoma compared to those with the default small circle.

Research paper thumbnail of Changes in adherence and associated factors among patients on newly introduced prostaglandin analog and timolol fixed-combination therapy

Patient Preference and Adherence, 2018

We investigated patient adherence and factors related to a newly introduced prostaglandin analog ... more We investigated patient adherence and factors related to a newly introduced prostaglandin analog and timolol fixed-combination eye drops (PGTFC). Patients and methods: The Glaucoma Research on Adherence to fixed-Combination Eye drops in Japan (GRACE) study group performed a nationwide prospective questionnaire survey. Participants in this study were patients with glaucoma who were scheduled to receive any type of PGTFC for the first time. The participants answered a questionnaire on the day of PGTFC introduction and again at a return visit 4-6 weeks after PGTFC introduction. The physicians in charge were asked to complete a separate questionnaire on the day of PGTFC introduction. One of two leaflets was randomly delivered to each participant before the description of the PGTFC. One leaflet explained how to correctly instill the eye drops, and the other explained the clinical meaning of intraocular pressure reduction in addition to explaining how to correctly instill the eye drops. Nonadherence was defined as forgetting to instill the eye drops one or more times during the week before the return visit. Results: In total, 3,597 patients (age, 68.4±12.2 years) met the study protocol requirements. PGTFC introduction significantly reduced the number of antiglaucoma eye drops from 1.93±0.78 to 1.34±0.54 (P0.0001) and significantly improved adherence (P0.00001). Factors significantly associated with nonadherence at the return visit included a history of nonadherence as reported by either the patient or their physician before introduction, acceptable instillation times as reported by the patient, and burdensome eye drop instillation as reported by the patient. No significant difference was observed between the two leaflets in terms of their effects on adherence. Conclusion: PGTFC significantly improved adherence and some of the factors that were significantly associated with adherence.

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

Investigative Ophthalmology & Visual Science, Mar 21, 2012

PURPOSE. To investigate the influence of glaucoma and myopia on the cross-sectional configuration... more PURPOSE. To investigate the influence of glaucoma and myopia on the cross-sectional configuration of the ␤-zone of peripapillary atrophy (PPA-␤) using spectral-domain optical coherence tomography (SD-OCT). METHODS. Cross-sectional B-scan images of PPA-␤ 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-␤ (84 POAG and 63 normal eyes; P ϭ 0.0012), the PPA bed was composed of straight (14 POAG and 27 normal eyes) or downward-curved (19 and 8 eyes) Bruch's 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 ϭ 0.034) and less myopic refractive error (OR, 1.43; P ϭ 0.009) were significantly associated with straight-BM-type, presence of POAG (OR, 5.74; P ϭ 0.008) and less myopic refractive error (OR, 3.02; P Ͻ 0.001) with curved-BM-type, and myopic refractive error (OR, 0.34; P Ͻ 0.001) with BM-defect-type. Within the PPA-␤ region, all retinal layers except for the nerve fiber layer frequently disappeared before reaching the disc edge, showing no significant intergroup difference (P Ͼ 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.

Research paper thumbnail of Glaucoma-Induced Optic Disc Morphometric Changes and Glaucoma Diagnostic Ability of Heidelberg Retina Tomograph II in Highly Myopic Eyes

PLoS ONE, 2014

Purpose: This study was performed to first investigate the morphological differences in the optic... more Purpose: This study was performed to first investigate the morphological differences in the optic nerve head between highly myopic non-glaucomatous controls and highly myopic glaucomatous eyes in comparison with the differences between emmetropic non-glaucomatous controls and emmetropic glaucomatous eyes using confocal scanning laser ophthalmoscopy. Further, the ability of the apparatus in glaucoma diagnosis in highly myopic eyes was compared with that in emmetropic eyes. Methods: Healthy subjects and age-matched patients with early-stage open-angle glaucoma were divided into two groups: emmetropic eyes (21.0 to +1.0 diopters) and highly myopic eyes (212.0 to 25.0 diopters).The participants were comprised of 65 emmetropic normal eyes, 59 emmetropic glaucomatous eyes, 62 highly myopic normal eyes, and 68 highly myopic glaucomatous eyes and eyes with pathologic myopia were carefully excluded. Confocal scanning laser tomographic parameters were compared among all subjects after adjustment for age and disc area. The ROC curves and sensitivity and specificity for glaucoma detection using several clinical methods were then compared between the emmetropic and highly myopic eyes. Results: Rim area, cup/disc area ratio, mean cup depth, and cup shape measure of glaucoma eyes are significantly different from those of normal eyes in both highly myopic eyes and emmetropic eyes. Methodological overestimation of retinal nerve fiber layer cross sectional area due to optic disc tilting was suggested in the highly myopic eyes. The diagnostic performance of glaucoma using several discriminant methods significantly deteriorated in the highly myopic eyes. Conclusions: In the highly myopic glaucomatous eyes, confocal scanning laser tomographic parameters were significantly different from that of non-glaucomatous highly myopic eyes but diagnostic performance of glaucoma was deteriorated than that in emmetropic eyes. These findings demonstrate the utility and limitations of the apparatus in diagnosing glaucoma in highly myopic patients.

Research paper thumbnail of Combining Multiple HRT Parameters Using the 'Random Forests' Method Improves the Diagnostic Accuracy of Glaucoma in Emmetropic and Highly Myopic Eyes

Investigative Ophthalmology & Visual Science, 2014

PURPOSE. To combine multiple Heidelberg Retina Tomograph (HRT) parameters using the Random Forest... more PURPOSE. To combine multiple Heidelberg Retina Tomograph (HRT) parameters using the Random Forests classifier to diagnose glaucoma, both in highly and physiologically myopic (highly myopic) eyes and emmetropic eyes. METHODS. Subjects consisted of healthy subjects and age-matched patients with open-angle glaucoma in emmetropic (À1.0 to þ1.0 diopters [D], 63 and 59 subjects, respectively) and highly myopic eyes (À10.0 to À5.0 D, 56 and 64 subjects, respectively). First, area under the receiver operating characteristic curve (AUC) was derived using 84 HRT global and sectorial parameters and the representative HRT raw parameter (largest AUC) was identified. Then, the Random Forests method was carried out using age, refractive error, and 84 HRT parameters. The AUCs were also derived using the following: (1) Frederick S. Mikelberg discriminant function (FSM) score, (2) Reinhard O.W. Burk discriminant function (RB) score, (3) Moorfields regression analysis (MRA) score, and (4) glaucoma probability score (GPS). RESULTS. In combined emmetropic and highly myopic population, AUC with Random Forests method (0.96) was significantly larger than AUCs with the representative HRT raw parameter (vertical cup-to-disc ratio [global], 0.89), FSM (0.90), RB (0.83), MRA (0.87), and GPS (0.81) (P < 0.001). Similarly, AUC with the Random Forests method was significantly (P < 0.05) larger than these other parameters, both in emmetropic and highly myopic groups. Also, the Random Forests method achieved partial AUCs above 80%/90% significantly (P < 0.05) larger than any other HRT parameters in all populations. CONCLUSIONS. Evaluating multiple HRT parameters using the Random Forests classifier provided accurate diagnosis of glaucoma, both in emmetropic and highly myopic eyes.

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

Investigative Ophthalmology & Visual Science, 2010

PURPOSE. To evaluate the cross-sectional configurations of peripapillary atrophy (PPA)-␣ and-␤ in... more PURPOSE. To evaluate the cross-sectional configurations of peripapillary atrophy (PPA)-␣ and-␤ 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-␣ and-␤ were identified in color photographs of the optic disc. Cross-sectional B-mode images of the peripapillary retina and sclera, including PPA-␣ and-␤ obtained with SD-OCT, were analyzed. RESULTS. Of 120 normal eyes, 120 (100%) had PPA-␣ and 90 (75%) had PPA-␤. 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), innerouter segments (IS-OS), and retinal pigment epithelium(RPE)/ Bruch's membrane complex were significantly more commonly absent before the optic disc edge within the PPA-␤ compared with areas outside the PPA-␤ (P Ͻ 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-Bruch's 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 ϭ 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.

Research paper thumbnail of Circle- and Grid-Wise Analyses of Peripapillary Nerve Fiber Layers by Spectral Domain Optical Coherence Tomography in Early-Stage Glaucoma

Investigative Ophthalmology & Visual Science, 2013

Circle-and grid-wise analyses of peripapillary nerve fiber layers by spectral domain optical cohe... more Circle-and grid-wise analyses of peripapillary nerve fiber layers by spectral domain optical coherence tomography in early-stage glaucoma.

Research paper thumbnail of The Additive Effect of ROCK Inhibitor on Prostaglandin-Treated Japanese Patients with Glaucoma Indicating 15 mmHg and Under: ROCK U-15

Advances in Therapy, 2021

Introduction: We aimed to evaluate the additional effects and safety of a Rho-associated protein ... more Introduction: We aimed to evaluate the additional effects and safety of a Rho-associated protein kinase (ROCK) inhibitor, ripasudil hydrochloride hydrate, in Japanese patients with primary open-angle glaucoma (POAG) with an intraocular pressure (IOP) of at most 15 mmHg undergoing prostaglandin F 2a (FP) receptor agonist monotherapy (FP monotherapy). Methods: In this prospective observational study, 30 Japanese patients with POAG and IOP of at most 15 mmHg (mean age 59.4 years; 10 men) who were undergoing FP monotherapy in both eyes were administered an additional dose of ripasudil hydrochloride hydrate (GLANATEC ophthalmic solution 0.4%: ripasudil) in one eye. The following factors were investigated at 1 and 3 months after the initiation of ripasudil treatment: (1) magnitude of change in IOP between the treated and contralateral untreated eyes, (2) number of treated eyes showing 20% and 30% IOP reduction, (3) IOP difference between treated and contralateral untreated eyes, and (4) safety during the treatment period. Both (1) and (3) were analyzed using the mixedeffect model for repeated measurements. Results: The treated eyes showed significant reduction in IOP at 1 month (-1.92 mmHg, P \ 0.001) and 3 months (-1.81 mmHg, P \ 0.001). In contrast, contralateral untreated eyes did not show IOP reduction at 1 month (0.53 mmHg, P = 0.016) and 3 months (0.38 mmHg, P = 0.15). IOP reduction of-20% and-30% was achieved in 9 (30%) and 3 (10%) treated eyes, respectively. There were significant differences in IOP between the treated and contralateral untreated eyes at 1 month (-2.46 mmHg, P \ 0.001) and 3 months (-2.20 mmHg, P \ 0.001). Two patients experienced local adverse events (facial edema, one patient at week 1; blepharitis, one patient at 1 month); they recovered quickly after stopping ripasudil administration. Conclusion: In patients with POAG with an IOP of at most 15 mmHg undergoing FP monotherapy, the addition of ripasudil resulted in significant IOP lowering at 1 and 3 months. Ripasudil could be used to enhance the outcome of FP monotherapy. Trial registration: Registered UMIN ID: UMIN000030742.

Research paper thumbnail of A nationwide survey of factors influencing adherence to ocular hypotensive eyedrops in Japan

International ophthalmology, Jan 12, 2018

Few reports have investigated the status of adherence in Japan on a large scale. We aimed to inve... more Few reports have investigated the status of adherence in Japan on a large scale. We aimed to investigate the status of adherence to topical glaucoma treatment and its associated factors. A nationwide survey was conducted as a prospective fashion. Participants in this survey were subjects with primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension or pseudoexfoliation glaucoma who had been prescribed anti-glaucoma ophthalmic eyedrops and whose ophthalmologist considered prescribing any fixed combination of ocular hypotensive eyedrops for the first time between 2011 and 2012. Subjects and their attending ophthalmologists independently completed a questionnaire by utilizing a fixed combination of ocular hypotensive eyedrops. A total of 1358 ophthalmologists from 1071 medical institutions participated in this survey. We registered 4430 subjects (2049 males and 2381 females). In total, data from 3853 subjects (87.6%) were analyzed after inclusion of subjects based o...

Research paper thumbnail of Peripapillary retinal nerve fiber layer thickness determined by spectral-domain optical coherence tomography in ophthalmologically normal eyes

Archives of Ophthalmology, Nov 1, 2010

To evaluate the peripapillary distribution of retinal nerve fiber layer thickness (RNFLT) in norm... more 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 (PϽ.001, mixed linear model). Retinal nerve fiber layer thickness correlated with age in all diameters (partial correlation coefficient [PCC] = −0.40 to −0.32; PϽ .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 Յ .005). Sex and axial length did not correlate with RNFLT (PϾ.08). The decay slope was smallest in the temporal and largest in the nasal and inferior quadrants (PϽ.001); positively correlated with disc area (PCC=0.13 to 0.51; PՅ .04); and negatively correlated with RNFLT (PCC=−0.51 to −0.15; P Յ.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.

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

Ophthalmology, Aug 1, 2009

To evaluate the sensitivity and specificity of the 3 glaucoma classification programs, the FS Mik... more 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 ϭ 0.02ϳ0.003, chi-square test), and 86.7%, 96.1%, and 83.0% (PϽ0.0001) 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 (PϽ0.01ϳ0.002, 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.

Research paper thumbnail of Sensitivity and Specificity of FSM or RB Discriminant Function and Moorfields Regression Analysis

Research paper thumbnail of Spectral-domain optical coherence tomography of β-zone peripapillary atrophy: influence of myopia and glaucoma

Investigative ophthalmology & visual science, Jan 21, 2012

To investigate the influence of glaucoma and myopia on the cross-sectional configuration of the β... more 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). 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. 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) Bruch's 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 ...

Research paper thumbnail of Frequency Doubling Technology for Earlier Detection of Functional Damage in Standard Automated Perimetry-Normal Hemifield in Glaucoma With Low-to-Normal Pressure

Journal of Glaucoma, 2012

To compare the longitudinal change of frequency doubling technology (FDT) perimetry and standard ... more To compare the longitudinal change of frequency doubling technology (FDT) perimetry and standard automated perimetry (SAP) results in SAP-normal hemifield in open-angle glaucoma (OAG) eyes with low-to-normal intraocular pressure (IOP). FDT perimetry with the N-30 full threshold protocol and SAP using the Humphrey Field Analyzer with the 30-2 Swedish Interactive Threshold Algorithm-standard protocol were periodically performed for at least 3 years in 39 eyes of 39 OAG patients with low-to-normal IOP and visual field damage confined to only one hemifield. The time courses of the mean of the threshold values of FDT and the mean of total deviations (TDs) in SAP-normal and SAP-abnormal fields were analyzed using a linear mixed model. The average follow-up was 4.9 years and the average IOP during follow-up was 12.6 mm Hg with or without medication. The aging effect-corrected rate of change in the mean FDT threshold values was significantly negative (P=0.004) in the SAP-normal hemifield, whereas that of mean of TD values by SAP did not significantly differ. In the SAP-abnormal hemifield, the rate of change was significantly negative for both tests (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). The mean of the slope of the mean TD values in the SAP-abnormal hemifield was significantly more negative than that in the SAP-normal hemifield (P=0.011), whereas that of the mean FDT threshold values showed no significant difference between the 2 hemifields. FDT is useful for monitoring functional damage in the SAP-normal hemifield in OAG eyes with low-to-normal IOP.

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

Investigative Ophthalmology & Visual Science, 2011

PURPOSE. To identify sex-related differences and age-related changes in individual retinal layer ... more 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 OPLϩONL and OS were thickest in this area. Mean thicknesses of the INL and the OPLϩONL were significantly greater in men (P ϭ 0.002 and 0.001, respectively). However, mean RNFL thickness was greater in women (P ϭ 0.006). Thicknesses of the RNFL, GCL, IPL, INL, and IS correlated negatively with age. Thickness of the OPLϩONL was not correlated with age, and thickness of the OS correlated positively with age. Inner retinal (RNFLϩGCLϩIPL) thickness over the whole macula correlated negatively with age (P Ͻ 0.001), but outer retinal (OPLϩONLϩISϩOS) 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.

Research paper thumbnail of Reproducibility of Thickness Measurements of Macular Inner Retinal Layers Using SD-OCT With or Without Correction of Ocular Rotation

Investigative Ophthalmology & Visual Science, 2013

PURPOSE. To evaluate the intervisit reproducibility of spectral-domain optical coherence tomograp... more 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 (GCLþIPL) thickness; and ganglion cell complex (GCC) thicknesses (sum of mRNFLT and GCLþIPL 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 3 4.8-mm macular area and subareas (upper and lower halves, 2 3 2, 4 3 4, and 8 3 8 grids), and the 3608, upper, and lower halves mean cpRNFLT with and without correction of ocular rotation. RESULTS. The coefficients of variation (CVs) of GCLþIPL 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 (GCLþIPL) 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.

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

Investigative Ophthalmology & Visual Science, 2010

PURPOSE. To demonstrate the three-dimensional macular thickness distribution in normal subjects b... more 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 ϫ 6 mm) using SD-OCT in 248 normal eyes of 248 Japanese subjects. RESULTS. Mean foveal thickness was 222 Ϯ 19 m; it was significantly greater in men (226 Ϯ 19 m) than in women (218 Ϯ 18 m; P ϭ 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 Ͻ 0.001 and P ϭ 0.001-0.007) and in the temporal quadrant of the outer ring (3-6 mm; P Ͻ 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 Ͻ 0.001 and P ϭ 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. (In

Research paper thumbnail of Structure-function Relationship In Macular Area Of Normal Eyes

Research paper thumbnail of Macular Thickness Analysis By SD-OCT In Glaucoma Eyes With Hemi-retinal Damage

Research paper thumbnail of Atypical retardation pattern in measurements of scanning laser polarimetry and its relating factors

Eye, Dec 12, 2008

Purpose To assess the prevalence of atypical retardation pattern (ARP) in scanning laser polarime... more Purpose To assess the prevalence of atypical retardation pattern (ARP) in scanning laser polarimetry (SLP) with variable corneal compensation (VCC) and enhanced corneal compensation (ECC), and to evaluate the factors relating to typical scan score (TSS). Methods Measurements of SLP-VCC, SLP-ECC, and the Humphrey field analyzer (HFA) were performed in 105 normal subjects and 82 open-angle glaucoma (OAG) patients. ARP was defined as an SLP image with TSSo80. Results Prevalence of ARP with SLP-VCC was 13.3 and 14.6% in normal and OAG eyes, respectively, and that with SLP-ECC (2.9% and 1.2%) was lower than SLP-VCC (Po0.009). TSS with SLP-VCC was significantly correlated with age (partial correlation coefficient (PCC) ¼ À0.22, P ¼ 0.003) and refractive error (PCC ¼ 0.26, Po0.001) after adjusting for each other. TSS with SLP-ECC was significantly correlated with neither age nor refractive error (PCC ¼ À0.02, P ¼ 0.788; PCC ¼ 0.10, P ¼ 0.177, respectively). In OAG eyes, mean deviation (MD) of HFA was significantly correlated with TSS with SLP-VCC and SLP-ECC (PCC ¼ 0.35, P ¼ 0.001; PCC ¼ 0.23, P ¼ 0.039, respectively). In SLP-VCC, MD was significantly correlated with retinal nerve fibrr layer (RNFL) thickness only after excluding eyes with ARP (Po0.001). Conclusions ARP in SLP-VCC measurements was found in more than 10% of normal or glaucomatous eyes, and TSS was significantly lower in older subjects, more myopic eyes, or eyes with more advanced glaucomatous damage. The presence of ARP disturbs the accuracy of RNFL thickness measurement by SLP-VCC. In SLP-ECC measurements, prevalence of ARP was considerably lower and TSS was not affected by age or refractive error, suggesting the advantages of ECC in clinical practices.

Research paper thumbnail of Performance of GDx VCC in eyes with peripapillary atrophy: comparison of three circle sizes

Eye, Aug 4, 2006

Purpose A scanning laser polarimetry (GDx VCC) equips three different sized measurement circles. ... more Purpose A scanning laser polarimetry (GDx VCC) equips three different sized measurement circles. In eyes with peripapillary atrophy (PPA), the GDx measurement becomes inaccurate when the circle falls on PPA. The aim of this study was to evaluate performance of the three circles of GDx measurement in eyes with PPA. Methods Three different sized circles were compared regarding frequency of PPA, which fell on each circle in 282 open-angle glaucoma (OAG) eyes, reproducibility of GDx parameters in 24 normal and 22 OAG eyes, and ability to detect glaucoma in 50 normal and 50 OAG eyes. Results PPA was observed in 230 (82%) of 282 OAG eyes. PPA fell on the small circle (default setting), medium, and large circles in 119 (43%), 38 (14%), and 12 (4%) of the 280 OAG eyes. Reproducibility of GDx parameters was not significantly different among three circles in normal eyes (P40.05), whereas coefficients of reproducibility of TSNIT average (P ¼ 0.006) and superior average (P ¼ 0.035) were smaller in the smaller circles in OAG eyes. GDx parameters significantly correlated (Po0.001), but were significantly different (Po0.05) between the small and medium circles. The area under receiver operating characteristic curves for dividing OAG from normal eyes using GDx parameters was similar between the small and medium circles. Conclusions If the medium circles were used, obstructing influences of PPA on GDx measurement could be avoided more often in Japanese OAG eyes with similar reproducibility and comparable ability to detect glaucoma compared to those with the default small circle.

Research paper thumbnail of Changes in adherence and associated factors among patients on newly introduced prostaglandin analog and timolol fixed-combination therapy

Patient Preference and Adherence, 2018

We investigated patient adherence and factors related to a newly introduced prostaglandin analog ... more We investigated patient adherence and factors related to a newly introduced prostaglandin analog and timolol fixed-combination eye drops (PGTFC). Patients and methods: The Glaucoma Research on Adherence to fixed-Combination Eye drops in Japan (GRACE) study group performed a nationwide prospective questionnaire survey. Participants in this study were patients with glaucoma who were scheduled to receive any type of PGTFC for the first time. The participants answered a questionnaire on the day of PGTFC introduction and again at a return visit 4-6 weeks after PGTFC introduction. The physicians in charge were asked to complete a separate questionnaire on the day of PGTFC introduction. One of two leaflets was randomly delivered to each participant before the description of the PGTFC. One leaflet explained how to correctly instill the eye drops, and the other explained the clinical meaning of intraocular pressure reduction in addition to explaining how to correctly instill the eye drops. Nonadherence was defined as forgetting to instill the eye drops one or more times during the week before the return visit. Results: In total, 3,597 patients (age, 68.4±12.2 years) met the study protocol requirements. PGTFC introduction significantly reduced the number of antiglaucoma eye drops from 1.93±0.78 to 1.34±0.54 (P0.0001) and significantly improved adherence (P0.00001). Factors significantly associated with nonadherence at the return visit included a history of nonadherence as reported by either the patient or their physician before introduction, acceptable instillation times as reported by the patient, and burdensome eye drop instillation as reported by the patient. No significant difference was observed between the two leaflets in terms of their effects on adherence. Conclusion: PGTFC significantly improved adherence and some of the factors that were significantly associated with adherence.

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

Investigative Ophthalmology & Visual Science, Mar 21, 2012

PURPOSE. To investigate the influence of glaucoma and myopia on the cross-sectional configuration... more PURPOSE. To investigate the influence of glaucoma and myopia on the cross-sectional configuration of the ␤-zone of peripapillary atrophy (PPA-␤) using spectral-domain optical coherence tomography (SD-OCT). METHODS. Cross-sectional B-scan images of PPA-␤ 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-␤ (84 POAG and 63 normal eyes; P ϭ 0.0012), the PPA bed was composed of straight (14 POAG and 27 normal eyes) or downward-curved (19 and 8 eyes) Bruch's 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 ϭ 0.034) and less myopic refractive error (OR, 1.43; P ϭ 0.009) were significantly associated with straight-BM-type, presence of POAG (OR, 5.74; P ϭ 0.008) and less myopic refractive error (OR, 3.02; P Ͻ 0.001) with curved-BM-type, and myopic refractive error (OR, 0.34; P Ͻ 0.001) with BM-defect-type. Within the PPA-␤ region, all retinal layers except for the nerve fiber layer frequently disappeared before reaching the disc edge, showing no significant intergroup difference (P Ͼ 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.

Research paper thumbnail of Glaucoma-Induced Optic Disc Morphometric Changes and Glaucoma Diagnostic Ability of Heidelberg Retina Tomograph II in Highly Myopic Eyes

PLoS ONE, 2014

Purpose: This study was performed to first investigate the morphological differences in the optic... more Purpose: This study was performed to first investigate the morphological differences in the optic nerve head between highly myopic non-glaucomatous controls and highly myopic glaucomatous eyes in comparison with the differences between emmetropic non-glaucomatous controls and emmetropic glaucomatous eyes using confocal scanning laser ophthalmoscopy. Further, the ability of the apparatus in glaucoma diagnosis in highly myopic eyes was compared with that in emmetropic eyes. Methods: Healthy subjects and age-matched patients with early-stage open-angle glaucoma were divided into two groups: emmetropic eyes (21.0 to +1.0 diopters) and highly myopic eyes (212.0 to 25.0 diopters).The participants were comprised of 65 emmetropic normal eyes, 59 emmetropic glaucomatous eyes, 62 highly myopic normal eyes, and 68 highly myopic glaucomatous eyes and eyes with pathologic myopia were carefully excluded. Confocal scanning laser tomographic parameters were compared among all subjects after adjustment for age and disc area. The ROC curves and sensitivity and specificity for glaucoma detection using several clinical methods were then compared between the emmetropic and highly myopic eyes. Results: Rim area, cup/disc area ratio, mean cup depth, and cup shape measure of glaucoma eyes are significantly different from those of normal eyes in both highly myopic eyes and emmetropic eyes. Methodological overestimation of retinal nerve fiber layer cross sectional area due to optic disc tilting was suggested in the highly myopic eyes. The diagnostic performance of glaucoma using several discriminant methods significantly deteriorated in the highly myopic eyes. Conclusions: In the highly myopic glaucomatous eyes, confocal scanning laser tomographic parameters were significantly different from that of non-glaucomatous highly myopic eyes but diagnostic performance of glaucoma was deteriorated than that in emmetropic eyes. These findings demonstrate the utility and limitations of the apparatus in diagnosing glaucoma in highly myopic patients.

Research paper thumbnail of Combining Multiple HRT Parameters Using the 'Random Forests' Method Improves the Diagnostic Accuracy of Glaucoma in Emmetropic and Highly Myopic Eyes

Investigative Ophthalmology & Visual Science, 2014

PURPOSE. To combine multiple Heidelberg Retina Tomograph (HRT) parameters using the Random Forest... more PURPOSE. To combine multiple Heidelberg Retina Tomograph (HRT) parameters using the Random Forests classifier to diagnose glaucoma, both in highly and physiologically myopic (highly myopic) eyes and emmetropic eyes. METHODS. Subjects consisted of healthy subjects and age-matched patients with open-angle glaucoma in emmetropic (À1.0 to þ1.0 diopters [D], 63 and 59 subjects, respectively) and highly myopic eyes (À10.0 to À5.0 D, 56 and 64 subjects, respectively). First, area under the receiver operating characteristic curve (AUC) was derived using 84 HRT global and sectorial parameters and the representative HRT raw parameter (largest AUC) was identified. Then, the Random Forests method was carried out using age, refractive error, and 84 HRT parameters. The AUCs were also derived using the following: (1) Frederick S. Mikelberg discriminant function (FSM) score, (2) Reinhard O.W. Burk discriminant function (RB) score, (3) Moorfields regression analysis (MRA) score, and (4) glaucoma probability score (GPS). RESULTS. In combined emmetropic and highly myopic population, AUC with Random Forests method (0.96) was significantly larger than AUCs with the representative HRT raw parameter (vertical cup-to-disc ratio [global], 0.89), FSM (0.90), RB (0.83), MRA (0.87), and GPS (0.81) (P < 0.001). Similarly, AUC with the Random Forests method was significantly (P < 0.05) larger than these other parameters, both in emmetropic and highly myopic groups. Also, the Random Forests method achieved partial AUCs above 80%/90% significantly (P < 0.05) larger than any other HRT parameters in all populations. CONCLUSIONS. Evaluating multiple HRT parameters using the Random Forests classifier provided accurate diagnosis of glaucoma, both in emmetropic and highly myopic eyes.

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

Investigative Ophthalmology & Visual Science, 2010

PURPOSE. To evaluate the cross-sectional configurations of peripapillary atrophy (PPA)-␣ and-␤ in... more PURPOSE. To evaluate the cross-sectional configurations of peripapillary atrophy (PPA)-␣ and-␤ 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-␣ and-␤ were identified in color photographs of the optic disc. Cross-sectional B-mode images of the peripapillary retina and sclera, including PPA-␣ and-␤ obtained with SD-OCT, were analyzed. RESULTS. Of 120 normal eyes, 120 (100%) had PPA-␣ and 90 (75%) had PPA-␤. 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), innerouter segments (IS-OS), and retinal pigment epithelium(RPE)/ Bruch's membrane complex were significantly more commonly absent before the optic disc edge within the PPA-␤ compared with areas outside the PPA-␤ (P Ͻ 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-Bruch's 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 ϭ 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.

Research paper thumbnail of Circle- and Grid-Wise Analyses of Peripapillary Nerve Fiber Layers by Spectral Domain Optical Coherence Tomography in Early-Stage Glaucoma

Investigative Ophthalmology & Visual Science, 2013

Circle-and grid-wise analyses of peripapillary nerve fiber layers by spectral domain optical cohe... more Circle-and grid-wise analyses of peripapillary nerve fiber layers by spectral domain optical coherence tomography in early-stage glaucoma.

Research paper thumbnail of The Additive Effect of ROCK Inhibitor on Prostaglandin-Treated Japanese Patients with Glaucoma Indicating 15 mmHg and Under: ROCK U-15

Advances in Therapy, 2021

Introduction: We aimed to evaluate the additional effects and safety of a Rho-associated protein ... more Introduction: We aimed to evaluate the additional effects and safety of a Rho-associated protein kinase (ROCK) inhibitor, ripasudil hydrochloride hydrate, in Japanese patients with primary open-angle glaucoma (POAG) with an intraocular pressure (IOP) of at most 15 mmHg undergoing prostaglandin F 2a (FP) receptor agonist monotherapy (FP monotherapy). Methods: In this prospective observational study, 30 Japanese patients with POAG and IOP of at most 15 mmHg (mean age 59.4 years; 10 men) who were undergoing FP monotherapy in both eyes were administered an additional dose of ripasudil hydrochloride hydrate (GLANATEC ophthalmic solution 0.4%: ripasudil) in one eye. The following factors were investigated at 1 and 3 months after the initiation of ripasudil treatment: (1) magnitude of change in IOP between the treated and contralateral untreated eyes, (2) number of treated eyes showing 20% and 30% IOP reduction, (3) IOP difference between treated and contralateral untreated eyes, and (4) safety during the treatment period. Both (1) and (3) were analyzed using the mixedeffect model for repeated measurements. Results: The treated eyes showed significant reduction in IOP at 1 month (-1.92 mmHg, P \ 0.001) and 3 months (-1.81 mmHg, P \ 0.001). In contrast, contralateral untreated eyes did not show IOP reduction at 1 month (0.53 mmHg, P = 0.016) and 3 months (0.38 mmHg, P = 0.15). IOP reduction of-20% and-30% was achieved in 9 (30%) and 3 (10%) treated eyes, respectively. There were significant differences in IOP between the treated and contralateral untreated eyes at 1 month (-2.46 mmHg, P \ 0.001) and 3 months (-2.20 mmHg, P \ 0.001). Two patients experienced local adverse events (facial edema, one patient at week 1; blepharitis, one patient at 1 month); they recovered quickly after stopping ripasudil administration. Conclusion: In patients with POAG with an IOP of at most 15 mmHg undergoing FP monotherapy, the addition of ripasudil resulted in significant IOP lowering at 1 and 3 months. Ripasudil could be used to enhance the outcome of FP monotherapy. Trial registration: Registered UMIN ID: UMIN000030742.

Research paper thumbnail of A nationwide survey of factors influencing adherence to ocular hypotensive eyedrops in Japan

International ophthalmology, Jan 12, 2018

Few reports have investigated the status of adherence in Japan on a large scale. We aimed to inve... more Few reports have investigated the status of adherence in Japan on a large scale. We aimed to investigate the status of adherence to topical glaucoma treatment and its associated factors. A nationwide survey was conducted as a prospective fashion. Participants in this survey were subjects with primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension or pseudoexfoliation glaucoma who had been prescribed anti-glaucoma ophthalmic eyedrops and whose ophthalmologist considered prescribing any fixed combination of ocular hypotensive eyedrops for the first time between 2011 and 2012. Subjects and their attending ophthalmologists independently completed a questionnaire by utilizing a fixed combination of ocular hypotensive eyedrops. A total of 1358 ophthalmologists from 1071 medical institutions participated in this survey. We registered 4430 subjects (2049 males and 2381 females). In total, data from 3853 subjects (87.6%) were analyzed after inclusion of subjects based o...

Research paper thumbnail of Peripapillary retinal nerve fiber layer thickness determined by spectral-domain optical coherence tomography in ophthalmologically normal eyes

Archives of Ophthalmology, Nov 1, 2010

To evaluate the peripapillary distribution of retinal nerve fiber layer thickness (RNFLT) in norm... more 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 (PϽ.001, mixed linear model). Retinal nerve fiber layer thickness correlated with age in all diameters (partial correlation coefficient [PCC] = −0.40 to −0.32; PϽ .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 Յ .005). Sex and axial length did not correlate with RNFLT (PϾ.08). The decay slope was smallest in the temporal and largest in the nasal and inferior quadrants (PϽ.001); positively correlated with disc area (PCC=0.13 to 0.51; PՅ .04); and negatively correlated with RNFLT (PCC=−0.51 to −0.15; P Յ.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.

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

Ophthalmology, Aug 1, 2009

To evaluate the sensitivity and specificity of the 3 glaucoma classification programs, the FS Mik... more 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 ϭ 0.02ϳ0.003, chi-square test), and 86.7%, 96.1%, and 83.0% (PϽ0.0001) 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 (PϽ0.01ϳ0.002, 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.

Research paper thumbnail of Sensitivity and Specificity of FSM or RB Discriminant Function and Moorfields Regression Analysis

Research paper thumbnail of Spectral-domain optical coherence tomography of β-zone peripapillary atrophy: influence of myopia and glaucoma

Investigative ophthalmology & visual science, Jan 21, 2012

To investigate the influence of glaucoma and myopia on the cross-sectional configuration of the β... more 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). 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. 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) Bruch's 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 ...

Research paper thumbnail of Frequency Doubling Technology for Earlier Detection of Functional Damage in Standard Automated Perimetry-Normal Hemifield in Glaucoma With Low-to-Normal Pressure

Journal of Glaucoma, 2012

To compare the longitudinal change of frequency doubling technology (FDT) perimetry and standard ... more To compare the longitudinal change of frequency doubling technology (FDT) perimetry and standard automated perimetry (SAP) results in SAP-normal hemifield in open-angle glaucoma (OAG) eyes with low-to-normal intraocular pressure (IOP). FDT perimetry with the N-30 full threshold protocol and SAP using the Humphrey Field Analyzer with the 30-2 Swedish Interactive Threshold Algorithm-standard protocol were periodically performed for at least 3 years in 39 eyes of 39 OAG patients with low-to-normal IOP and visual field damage confined to only one hemifield. The time courses of the mean of the threshold values of FDT and the mean of total deviations (TDs) in SAP-normal and SAP-abnormal fields were analyzed using a linear mixed model. The average follow-up was 4.9 years and the average IOP during follow-up was 12.6 mm Hg with or without medication. The aging effect-corrected rate of change in the mean FDT threshold values was significantly negative (P=0.004) in the SAP-normal hemifield, whereas that of mean of TD values by SAP did not significantly differ. In the SAP-abnormal hemifield, the rate of change was significantly negative for both tests (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). The mean of the slope of the mean TD values in the SAP-abnormal hemifield was significantly more negative than that in the SAP-normal hemifield (P=0.011), whereas that of the mean FDT threshold values showed no significant difference between the 2 hemifields. FDT is useful for monitoring functional damage in the SAP-normal hemifield in OAG eyes with low-to-normal IOP.

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

Investigative Ophthalmology & Visual Science, 2011

PURPOSE. To identify sex-related differences and age-related changes in individual retinal layer ... more 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 OPLϩONL and OS were thickest in this area. Mean thicknesses of the INL and the OPLϩONL were significantly greater in men (P ϭ 0.002 and 0.001, respectively). However, mean RNFL thickness was greater in women (P ϭ 0.006). Thicknesses of the RNFL, GCL, IPL, INL, and IS correlated negatively with age. Thickness of the OPLϩONL was not correlated with age, and thickness of the OS correlated positively with age. Inner retinal (RNFLϩGCLϩIPL) thickness over the whole macula correlated negatively with age (P Ͻ 0.001), but outer retinal (OPLϩONLϩISϩOS) 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.

Research paper thumbnail of Reproducibility of Thickness Measurements of Macular Inner Retinal Layers Using SD-OCT With or Without Correction of Ocular Rotation

Investigative Ophthalmology & Visual Science, 2013

PURPOSE. To evaluate the intervisit reproducibility of spectral-domain optical coherence tomograp... more 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 (GCLþIPL) thickness; and ganglion cell complex (GCC) thicknesses (sum of mRNFLT and GCLþIPL 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 3 4.8-mm macular area and subareas (upper and lower halves, 2 3 2, 4 3 4, and 8 3 8 grids), and the 3608, upper, and lower halves mean cpRNFLT with and without correction of ocular rotation. RESULTS. The coefficients of variation (CVs) of GCLþIPL 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 (GCLþIPL) 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.

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

Investigative Ophthalmology & Visual Science, 2010

PURPOSE. To demonstrate the three-dimensional macular thickness distribution in normal subjects b... more 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 ϫ 6 mm) using SD-OCT in 248 normal eyes of 248 Japanese subjects. RESULTS. Mean foveal thickness was 222 Ϯ 19 m; it was significantly greater in men (226 Ϯ 19 m) than in women (218 Ϯ 18 m; P ϭ 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 Ͻ 0.001 and P ϭ 0.001-0.007) and in the temporal quadrant of the outer ring (3-6 mm; P Ͻ 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 Ͻ 0.001 and P ϭ 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. (In