Evaluation of anterior chamber angle by van Herick grading and ultrasound biomicroscopy in light and dark conditions for finding appositional angle closure and plateau iris configuration.

PURPOSE: To evaluate association of the van Herick (VH) grades with the ultrasound biomicroscopic (UBM) parameters, appositional irido-trabecular contact (A-ITC) and plateau iris (PI) in a randomly sampled population. METHODS: A 10% random sample of all residents aged 40 or older of the Kumejima study underwent UBM under dark and light conditions in the four quadrants of right eyes. RESULTS: Of 301 right eyes with eligible UBM images, 101 (33.6%) and 200 (66.4%) were classified as VH ≤ 2 and VH ≥ 3, respectively. The UBM parameters on angle width and ciliary body configuration were significantly different between VH ≤ 2 and VH ≥ 3 eyes (p < 0.001). A-ITC was found in at least one quadrant in 54.5% and 75.2% of VH ≤ 2 eyes under light and dark conditions, respectively; and 20.5% and 45.5% of VH ≥ 3 eyes. When 'VH ≤ 2' was used to screen eyes with A-ITC in three or more quadrants, the sensitivity and specificity were 74.1% and 75.3%, respectively. A-ITC was significantly associated with shallower anterior chamber (p = 0.018) and higher intraocular pressure (p = 0.044) in VH ≥ 3 eyes. Plateau iris (PI) was found in 15.8% and 6.0% of VH ≤ 2 and VH ≥ 3 eyes, respectively. Plateau iris (PI) was significantly associated with the UBM parameters on angle width and ciliary body configuration. When 'VH ≤ 2' was used to screen eyes with PI, the sensitivity and specificity were 57.1% and 68.9%, respectively. CONCLUSIONS: The VH grade of ≤2 and ≥3 showed significant association with UBM angle width and ciliary body configuration parameters. The VH ≤ 2 criterion should be useful for screening of A-ITC and PI.

Spatial and Temporal Relationship between Structural Progression and Disc Hemorrhage in Glaucoma in a 3-Year Prospective Study.

PURPOSE: To investigate the spatial and temporal relationship between disc hemorrhage (DH) and structural progression in patients with primary open-angle glaucoma (POAG) in a 3-year prospective study. DESIGN: Prospective cohort study. PARTICIPANTS: Patients with POAG and intraocular pressure of ≤18 mmHg on monotherapy with prostaglandin analogs. METHODS: Fundus photographs were taken at baseline and every 3 months for 3 years. Disc hemorrhage and structural progression were detected independently by flicker chronoscopy. If present, clock-hour disc locations in the right eye format and colocalization were determined. Statistical comparisons were based on mixed-effects models accounting for the correlation between different disc sites within the same eye and between fellow eyes in the same patient. MAIN OUTCOME MEASURES: Relationship between DH and structural progression at the same site. RESULTS: Among 195 eyes of 115 patients, DH appeared in 85 sites in 65 eyes (33.3%) and was most frequently at the 7 o'clock disc location (29.4%, P < 0.0001). Structural progression occurred at 63 sites of 52 eyes (26.7%) comparably in both superior and inferior hemidiscs, which was mostly detected as widening of the retinal nerve fiber layer defects (RNFLDs). Temporal RNFLD widening was common, whereas nasal widening occurred exclusively in the vertical quadrants (P = 0.035). Of 41 progression sites in eyes with DH, 28 sites (68.2%) had both DH and progression. Progression sites with DH were less common in the superior quadrant than in the inferior and temporal quadrants (P = 0.011). Eyes with DH had a significantly higher risk of progression than eyes without DH (hazard ratio, 3.72; P < 0.0001). For 63 progression sites, DH recurrence and more visits with DH at the progression site were significantly associated with shorter time to progression from baseline (P = 0.021, P = 0.017, respectively), whereas colocalization of DH and progression were not. CONCLUSIONS: In a 3-year prospective study with a Japanese POAG cohort, the relationship between DH and RNFLD and the pattern of RNFLD progression differed by disc location. The association between more frequent DH at the progression site and shorter time to progression indicates that DH may reflect vulnerability to same-site structural deterioration.

Pseudoexfoliation syndrome and relating factors in a rural Japanese population: the Kumejima Study.

PURPOSE: To report the prevalence of pseudoexfoliation (PEX) syndrome and glaucoma associated with PEX (PEX-G) and their relating factors of them in a south-western island of Japan. METHODS: A population-based survey of all residents aged ≥ 40 years was conducted in Kumejima, Okinawa, Japan, and 3762 subjects (participation rate, 81.2%) underwent detailed ophthalmic examinations. Presence of PEX material on the lens capsule, iris surface and/or pupillary margin was determined by slit-lamp biomicroscopy. Glaucoma was diagnosed according to the criteria of the International Society of Geographical and Epidemiological Ophthalmology. RESULTS: In subjects aged ≥ 40 years, prevalence rates of PEX syndrome, PEX without glaucoma and PEX-G in at least one eye were 1.5% (95% confidence interval [CI]: 1.0-1.9%), 1.3% (95% CI: 0.9-1.7%) and 0.1% (95% CI: 0.0-0.2%), respectively, excluding eyes after cataract surgery; and 2.8% (95% CI: 2.3-3.3%), 2.2% (95% CI: 1.8-2.6 %) and 0.4% (95% CI: 0.2-0.6%), respectively, including eyes after cataract surgery. Cataract surgery had been performed in 61% of subjects with PEX in at least one eye; presence of PEX showed no significant effects on the intraocular pressure (IOP). A multivariate analysis showed that PEX was associated with older age (p < 0.0001, odds ratio: 1.10 [95% CI: 1.07-1.13]) and working outdoors (p = 0.0395, odds ratio: 2.18 [95% CI: 0.99-4.82]). CONCLUSIONS: The prevalence rates of PEX syndrome and PEX-G in a south-western island of Japan were reported. PEX showed no significant effect on IOP, and age and working outdoors were significantly related with PEX.

Refractive errors in an elderly rural Japanese population: The Kumejima study.

The prevalence of refractive errors, which closely relates to visual function difficulties, several ocular disorders, and decreased quality of life, varies among countries and populations. One of the highest prevalence of myopia (spherical equivalent [SE] < -0.5 diopters [D], 41.8%) has been reported in an urban city (Tajimi) in central Japan. Here, we assess refractive conditions in a rural southwestern island (Kumejima) of Japan, where a high prevalence of glaucoma, especially angle-closure glaucoma, has been found. In Kumejima, the prevalence of myopia (SE < -0.5 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) were 29.5%, 1.9%, 34.1%, 38.8%, and 15.5%, respectively. Myopia decreased with age up to 70 years old but increased slightly thereafter, whereas hyperopia increased up to 70 years old and was unchanged thereafter. The prevalence of astigmatism and anisometropia was higher in older subjects. The prevalence of myopia and high myopia was higher than most of white, Hispanic, and other Asian populations, while was considerably lower than in the urban city of Japan. The high prevalence of hyperopia should be associated with high prevalence of angle closure glaucoma in this island.

Beta-peripapillary atrophy of the optic disc and its determinants in Japanese eyes: a population-based study.

PURPOSES: To assess ß-zone of peripapillary atrophy (ß-PPA) and its relationship between systemic and ocular factors, especially glaucoma, in a Japanese population. METHODS: Fundus photographs obtained from 2129 normal, 84 primary open-angle glaucoma (POAG) and 10 primary angle closure glaucoma subjects from 3021 participants aged 40 years or older in the Tajimi Study were analysed planimetrically. If both eyes of a subject met inclusion criteria, one eye was randomly chosen. RESULTS: The presence rates of ß-PPA were 54.7 and 77.4% (p < 0.001) and ß-PPA area averaged 0.67 and 1.06 mm2 (p < 0.001), in normal and POAG eyes, respectively. Myopia was closely related to disc ovality and ß-PPA. In normal eyes, logistic analysis showed that the presence of ß-PPA was correlated with older age, female gender, myopic refraction, thicker central corneal thickness (CCT), greater disc ovality and disc centre to fovea (disc-fovea) distance and lower intraocular pressure (IOP) (p = 0.039 ~ <0.001); and multiple regression analysis showed that ß-PPA area was correlated with older age, myopic refraction, greater disc area and ovality, disc-fovea distance and lower IOP (p = 0.004 ~ <0.001) after adjusting other factors. CONCLUSIONS: The presence and size of ß-PPA in normal eyes were correlated with older age, greater disc ovality and disc-fovea distance and lower IOP. Further, its presence was associated with female gender, thicker CCT and its size with greater disc area. ß-zone of peripapillary atrophy (ß-PPA) was also associated with POAG. These results provide reference data of the ß-PPA in a Japanese population and possibly indicate clinical importance of ß-PPA in glaucoma clinic.

Morphology of the optic disc in the Tajimi Study population.

PURPOSE: To assess optic disc morphology and disc-fovea distance (DF)/mean disc diameter (DD) ratio and related factors in Japanese subjects in a population-based setting. METHODS: Digital fundus photographs obtained from 2634 subjects, comprising 87% of 3021 participants aged 40 years or older in the Tajimi Study, a population-based glaucoma survey, were analyzed planimetrically. RESULTS: The disc size averaged 2.28 mm2, the ovality (maximal/minimal disc diameter ratio) 1.12 and the DF/DD ratio 2.94. After adjusting for other systemic and ocular factors, the disc size was correlated with the spherical equivalent refraction (SE), the ovality and DF/DD ratio correlated negatively with the SE and disc size (P < 0.0001). These parameters did not differ significantly between 2095 ophthalmologically normal eyes and 58 eyes with open angle glaucoma (OAG). The angle of the long axis of the discs with ovality of >1.10 was between 91° and 120° in 53% of the subject eyes. CONCLUSIONS: The reference data of disc morphology and DF/DD ratio in a Japanese population were obtained. SE showed significantly negative correlation with disc size, and disc size and SE showed significant negative correlation with ovality and DF/DD ratio. There was no significant difference between normal and OAG eyes evaluated by disc morphology and DF/DD ratio.

Reproducibility of Circumpapillary Retinal Nerve Fiber Layer Thickness Measurements Evaluated by Circle and Annulus Area With and Without Correction for Ocular Rotation.

PURPOSE: To compare the reproducibility of annulus area measurements of the circumpapillary retinal nerve fiber layer thickness (cpRNFLTannulus) using spectral-domain optical coherence tomography (SD-OCT) with that of conventional cpRNFLT (cpRNFLTring) measurements and evaluate the effect of correction of ocular rotation on the reproducibility. MATERIALS AND METHODS: Peripapillary SD-OCT raster scans were performed on 2 different days in 48 normal subjects and 59 patients with glaucoma using the Topcon OCT-1000. In the raster scan dataset, the cpRNFLTring and cpRNFLTannulus were averaged along a circle (3.4-mm diameter) and in an annulus area (diameters from 2.8 to 4.0 mm) centered on the barycenter of the disc. The measurement reproducibility, effects of ocular rotational correction, and factors affecting the reproducibility were studied. RESULTS: The intervisit reproducibility values, expressed as the coefficients of variation, for the cpRNFLTannulus, were significantly smaller than those for the cpRNFLTring measurements in sectors 30 degrees wide in glaucomatous eyes (P=0.006) and in sectors 10 degrees wide in normal and glaucomatous eyes (P<0.001). The ocular rotational angles averaged 7.1 and 7.2 degrees with intervisit differences of 1.4 and 1.8 degrees, respectively, in normal and glaucomatous eyes. Correction for the ocular rotation had little effect on the reproducibility. The mean deviation and cpRNFLT were correlated negatively with the coefficient of variation (ß=-0.93 to -0.83; P=0.027 to 0.028). CONCLUSIONS: The cpRNFLTannulus measurement yielded better reproducibility than the cpRNFLTring measurement, and multiple linear regression analysis showed that the more advanced the glaucomatous damage, the worse the intervisit reproducibility.

Correlation of Macular Ganglion Cell Complex Thickness With Frequency-doubling Technology Perimetry in Open-angle Glaucoma With Hemifield Defects.

PURPOSE: To understand better the relationship between the macular ganglion cell complex (mGCC) thickness and visual field sensitivity assessed by frequency-doubling technology (FDT) perimetry in the standard automated perimetry (SAP) normal hemifields of glaucomatous eyes, a model of preperimetric stage of glaucoma. PATIENTS AND METHODS: Thirty-four eyes of 34 patients with glaucomatous visual field defects restricted to the superior or inferior hemifield were included. Patients underwent the mGCC and circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurements using spectral domain optical coherence tomography and the FDT testing with N-30 full-threshold protocol. SAP and FDT sensitivity values were averaged in the area corresponding to thickness measurements and the thickness sensitivity relationships were assessed in the SAP normal and SAP abnormal halves (Spearman's rank correlation coefficient). RESULTS: FDT sensitivity was significantly correlated with both the cpRNFL and mGCC thicknesses either in the SAP normal (ρ=0.384 and 0.462, respectively) or in the SAP abnormal (ρ=0.402 and 0.717, respectively) halves. Correlation between the FDT sensitivity and the mGCC thickness was significantly (P=0.016) stronger than that with the cpRNFL thickness in the SAP abnormal half. SAP sensitivity was correlated significantly (ρ=0.570) only with the mGCC thickness in the SAP abnormal half. CONCLUSIONS: Similarly strong correlations of the mGCC thickness with the FDT sensitivity in the SAP normal and SAP abnormal halves, but not with the SAP sensitivity, indicates that the mGCC thickness and the FDT sensitivity may be more optimal structure-function indicator in preperimetric stage of glaucoma.

Diagnosis of Early-Stage Glaucoma by Grid-Wise Macular Inner Retinal Layer Thickness Measurement and Effect of Compensation of Disc-Fovea Inclination.

PURPOSE: To evaluate grid-wise analyses of macular inner retinal layer thicknesses and effect of compensation of disc-fovea inclination for diagnosing early-stage glaucoma. METHODS: Spectral-domain optical coherence tomography measurements over a 6.0 × 6.0-mm macular area were prospectively obtained in 104 eyes of 104 patients with early-stage glaucoma with a mean deviation of -1.8 ± 1.9 dB and 104 eyes of 104 age- and refraction-matched normal subjects. Macular retinal nerve fiber layer (mRNFL), ganglion cell-inner plexiform layer (GCIPL) combined, and ganglion cell complex (GCC) thickness of the entire area and each subdivided macular grid were determined to compare diagnostic capability for glaucoma using receiver operating characteristic curves and various normal cutoff values for each layer thickness and number of grids flagged as abnormal. Diagnostic capability was then compared with that of circumpapillary RNFL (cpRNFL) measurements. Effects of compensation of inclination of disc-fovea line by reconfiguration of the macular grid were also studied. RESULTS: Macular inner retinal layer analyses using 8 × 8 grids generally yielded higher diagnostic capability. Only the 8 × 8 grid GCC analyses using the various normal cutoff values yielded a sensitivity ≥ 0.90 with specificity ≥ 0.95 under several conditions in discriminating the glaucoma eyes. In glaucoma and normal eyes with both reliable cpRNFL and macular measurements, the best sensitivity/specificity were 0.98/0.95 for the 8 × 8 grid-mRNFL analysis and 0.93/0.96 for the 8 × 8 grid GCC analysis using various normal cutoff values, which were better than that (0.78/0.95) for clock-hour cpRNFL analysis (P = 0.001). Compensation of the disc-fovea inclination did not improve the diagnostic capability. CONCLUSIONS: Grid-wise analysis of macular GCC--especially using 8 × 8 grids and normative data-based cutoff values--was very useful for diagnosing early-stage glaucoma, though compensation of the disc-fovea inclination had little effect.

Diagnostic performance and reproducibility of circumpapillary retinal nerve fiber layer thickness measurement in 10-degree sectors in early stage glaucoma.

PURPOSE: To study the circumpapillary retinal nerve fiber layer thickness (cpRNFLT) in a 10°-wide sector using spectral-domain optical coherence tomography for diagnostic ability in early stage open-angle glaucoma (OAG). METHODS: cpRNFLT measurements (3.4-mm diameter centered on the disc) were obtained from 89 eyes with early stage OAG (mean deviation, -2.5 ± 1.8 decibels) and 89 age-matched normal eyes. The ability of 180°-, 90°-, 30°-, and 10°-wide cpRNFLT sectors in discriminating early stage OAG eyes was evaluated by calculating the area under the receiver-operating characteristic curves (AUCs) and sensitivity/specificity per diagnostic criteria with varying sector widths, normative data-based cpRNFLT cutoff levels and numbers of abnormal sectors. The intra- and inter-visit reproducibilities of the cpRNFLT 10°-sector measurements were studied in a separate group of eyes with normal and early stage OAG. RESULTS: The greatest AUC obtained using the cpRNFLT 10° sector, 0.924 (confidence interval, 0.875-0.958), did not differ significantly from those obtained with the 180°, 90°, and 30° sectors. Only calculations using the 10° sectors had sensitivities and specificities of 0.90 or higher with the best performance of the sensitivity/specificity of 0.92/0.94. These values tended to be better (P = 0.070) than with the 30° sectors, 0.85/0.94, which were also selected with several combinations of various cutoff levels and the number of abnormal sectors. The coefficients of variation for the intra- and inter-visit reproducibility of the 10°-sector measurements were 10 % or less in 32 and 24 of the 36 sectors. CONCLUSION: The cpRNFLT 10°-sector measurements showed reasonable reproducibility and identified eyes with early stage OAG with a sensitivity and specificity of 0.92/0.94.

Relationship between macular inner retinal layer thickness and corresponding retinal sensitivity in normal eyes.

PURPOSE: The correlation between standard automated perimetry (SAP) sensitivity and macular inner retinal layer thickness in eyes with glaucoma is well known. We examined whether the corresponding correlation is also significant in normal eyes. METHODS: One eye of each of 195 normal subjects was included. The average thickness of the macular ganglion cell-inner plexiform layers (GCIPL) and the macular retinal nerve fiber layer/GCIPL (ganglion cell complex, GCC) in four regions with 0.6-mm-diameter circular area corresponding to the four central test points of the Humphrey Field Analyzer 24-2 test program, adjusted for ganglion cell displacement, were measured using spectral-domain optical coherence tomography (SD-OCT) and correlated to the mean SAP sensitivity (in 1/Lambert scale) at the corresponding test points with a multiple regression analysis using age, refraction, disc size, sex, and laterality of the eye as other explanatory variables. RESULTS: In normal eyes, GCIPL and GCC thickness (in micrometers) showed significant correlation to SAP sensitivity in corresponding areas, with partial regression coefficients of 0.0016 (P = 0.036) and 0.0022 (P = 0.023), respectively. Other significantly correlated factors were age and GCIPL (-0.18, P = 0.000), age and GCC (-0.20, P = 0.000), and refraction and GCIPL (0.92, P = 0.012). Similar analyses at each of the four test points yielded essentially the same results, although partial correlation coefficients were not always significant. CONCLUSIONS: A thicker macular GCIPL or GCC was weakly but significantly associated with higher SAP sensitivity in the corresponding macular region in normal eyes.

Focal relationship between structure and function within the central 10 degrees in glaucoma.

PURPOSE: To investigate which measurements of inner macular thickness are the most useful for evaluating the focal relationship with visual sensitivity within the central 10° in glaucoma and which layers require correction for retinal ganglion cell (RGC) displacement. METHODS: Sixty eyes of 60 subjects with glaucoma were included. Sensitivity of each test point of 10-2 standard automated perimetry was compared with the thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), GCL+ inner plexiform layer (IPL), and RNFL+GCL+IPL (GCC), with and without RGC displacement, using Spearman's rank correlation coefficients. Visual sensitivity was evaluated by unlogged 1/Lambert (1/L) values. RESULTS: Retinal nerve fiber layer thickness correlated significantly with the sensitivities of all test points except for some in the papillomacular bundle region when adjusting for RGC displacement (rs = 0.287-0.767, P < 0.05). In the central 5.8°, the GCL and (GCL+IPL) thickness correlated significantly with the sensitivities of all test points when adjusting for RGC displacement (GCL: rs = 0.363-0.729, P < 0.01; (GCL+IPL): rs = 0.359-0.715, P < 0.01). The GCC thickness correlated significantly with the sensitivities of all 68 test points when adjusting for RGC displacement (rs = 0.359-0.767, P < 0.01). RGC displacement improved the correlation between sensitivity and GCL, (GCL+IPL), and GCC in the central 4 points (GCL: rs = from 0.270-0.470 to 0.421-0.540; (GCL+IPL): rs = from 0.195-0.450 to 0.381-0.549; GCC: rs = from 0.132-0.449 to 0.359-0.562). CONCLUSIONS: The GCC is the most useful parameter to evaluate structure and function within the central 10° in glaucoma. Adjusting for RGC displacement is essential to evaluate the relationship between structure of the GCL-related layer and function at the central macula.

Primary open-angle glaucoma in a population associated with high prevalence of primary angle-closure glaucoma: the Kumejima Study.

PURPOSE: To evaluate the prevalence of and risk factors for primary open-angle glaucoma (POAG) in a rural population of southwestern Japan. DESIGN: Population-based cross-sectional study. PARTICIPANTS: All residents 40 years of age and older in Kumejima, Okinawa, Japan. METHODS: Of the eligible 4632 residents 40 years of age and older, 3762 subjects (participant rate, 81.2%) underwent screening examinations, including visual acuity (VA) measurement, slit-lamp examination, Goldmann applanation tonometry, gonioscopy, undilated stereoscopic fundus photographs, autorefractometry, noncontact specular microscopy, pachymetry, and visual field (VF) testing using frequency-doubling technology. If glaucoma or other related ocular disorders were suspected, subjects were referred for definitive examinations including VF testing with the Humphrey Field Analyzer. The diagnosis of POAG was based on the criteria of the International Society for Geographical and Epidemiological Ophthalmology. MAIN OUTCOME MEASURES: Prevalence and risk factors of POAG. RESULTS: The prevalence of POAG was 4.0% (95% confidence interval [CI], 3.4%-4.7%); 82% of patients had an intraocular pressure (IOP) less than 22 mmHg, resulting in a prevalence of 3.3% (95% CI, 2.8%-3.9%). Because of POAG, 3 subjects had a VA worse than 20/400 in only 1 eye, and 1 subject had VA loss of worse than 20/400 bilaterally. The average IOP values (mean ± standard deviation) were 14.9 ± 3.2 and 14.6 ± 3.3 mmHg in the right and left eyes, respectively; the IOP values were higher in patients with POAG (15.4 ± 3.3 and 15.2 ± 3.3 mmHg, respectively) than in subjects without glaucoma (14.8 ± 3.1 and 14.4 ± 3.1 mmHg, respectively; P<0.045, Student t test). Multivariate analysis showed that male gender (P = 0.003), older age (P<0.001), higher IOP (P<0.001), longer axial length (P<0.001), and thinner central cornea (P = 0.006) were associated with POAG. CONCLUSIONS: High prevalence rates of POAG (4.0%) and POAG with normal IOP levels (3.3%), which were comparable with those on the Japanese mainland, were found in a southwestern rural island of Japan, where the prevalence of primary angle-closure glaucoma (previously reported as 2.2%) was considerably higher than on the Japanese mainland (0.6% in the Tajimi Study) or other countries. The risk factors for POAG included male gender, older age, higher IOP, myopia, and a thinner cornea.

Glaucoma-induced optic disc morphometric changes and glaucoma diagnostic ability of Heidelberg Retina Tomograph II in highly myopic eyes.

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 (-1.0 to +1.0 diopters) and highly myopic eyes (-12.0 to -5.0 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.

Factors related to future peripheral anterior synechiae formation on ultrasound biomicroscopy: 7-year follow-up in eyes with shallow peripheral anterior chambers.

PURPOSE: To study factors associated with future peripheral anterior synechiae (PAS) formation on ultrasound biomicroscopy (UBM) in eyes with a shallow peripheral anterior chamber. PATIENTS AND METHODS: Fifteen subjects with a shallow peripheral anterior chamber but no PAS in both eyes, in 2001, that had no medical or surgical intervention until 2008 were included in this study. The same examiners performed gonioscopy and UBM at the 3, 6, 9, and 12 o'clock limbal positions under dark and light conditions in 2001 and 2008. A masked examiner performed a quantitative evaluation of the angle configurations in the UBM images. The presence or absence of PAS was determined by compression gonioscopy. The UBM parameters and the number of appositional closures per eye were compared between PAS-positive eyes and PAS-negative eyes. RESULTS: One eye from 15 subjects were randomly selected and included in the analyses. The gonioscopic gradings and UBM parameters did not change significantly (P>0.1) between 2001 and 2008. Seven (47%; 95% confidence interval, 25-70) of 15 eyes developed PAS. In 2001, under dark conditions, the appositional angle closure in 3 to 4 quadrants was found more often (P=0.026) in 7 eyes where PAS developed during the following 7 years than in other 8 eyes. CONCLUSIONS: In eyes with a shallow peripheral anterior chamber but no PAS, PAS developed in 47% of eyes followed without intervention for 7 years. PAS was significantly more likely to develop in eyes with the appositional angle closure found in 3 to 4 quadrants under dark conditions.

Iridotrabecular contact observed using anterior segment three-dimensional OCT in eyes with a shallow peripheral anterior chamber.

PURPOSE: To evaluate the prevalence and range of iridotrabecular contact (ITC) in eyes with a shallow peripheral anterior chamber (AC) by using anterior segment swept-source optical coherence tomography (AS-SS-OCT) and to compare the results with those obtained with ultrasound biomicroscopy (UBM) and gonioscopy. METHODS: Forty-three shallow peripheral AC eyes in 43 consecutive patients underwent gonioscopy. Cross-sectional images throughout the angle circumference (i.e., 360°) were obtained with AS-SS-OCT (SS-1000 noncontact, noninvasive three-dimensional imaging system) and those of the peripheral AC at the 3, 6, 9, and 12 o'clock positions were obtained with UBM (UD-1000). RESULTS: ITC evaluated with AS-SS-OCT included all gonioscopically identified peripheral anterior synechia (PAS) in the area. With AS-SS-OCT, at least one ITC was found in 40 (93.0%) and 42 (97.7%) of the 43 eyes under light and dark conditions, respectively, whereas with UBM, at least one ITC was found in 22 (51.1%) and 36 (83.7%) of the 43 eyes under light and dark conditions. The prevalence of ITC in eyes with AS-SS-OCT was significantly higher than that with UBM under light conditions, but not under dark conditions (P = 0.0001, 0.07, respectively, sign test). The PAS-positive eyes had a significantly greater ITC range than the PAS-negative eyes under light conditions (P = 0.006), but not under dark conditions (P = 0.08). CONCLUSIONS: AS-SS-OCT detected all PAS and the prevalence of ITC detected by AS-SS-OCT in narrow angle eyes was markedly higher than previously thought. A relationship between the ITC range under light conditions and future PAS formation was suggested.

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

PURPOSE: To study diagnostic performances of circle- and grid-wise analyses of peripapillary retinal nerve fiber layer thickness (RNFLT) using spectral domain optical coherence tomography (SD-OCT) in early-stage glaucoma. METHODS: Eighty-nine open-angle glaucoma (OAG) eyes (mean deviation: 2.5 ± 1.8 dB) and 89 age-matched normal eyes were studied. Peripapillary RNFLT was analyzed using an SD-OCT raster scan in a 6.0 × 6.0-mm area. Averaged RNFLT was calculated over 0.1 × 0.1-, 0.21 × 0.21-, or 0.42 × 0.42-mm grids in the peripapillary area (grid method), or arcuate sector areas between 2.8- and 4.0-mm diameter circles (annulus method), or along a 3.4-mm diameter circle (circle method). Normative data-based cutoff values for averaged RNFLT and number of abnormal grid locations (grid method) or sectors (annulus or circle method) were varied. RESULTS: The grid method showed the best power of sensitivity/specificity of 0.94/0.96 with any five contiguous 0.21 × 0.21-mm grid locations with a 2.5 percentile cutoff, followed by the annulus method of 0.81/0.98, and the circle method of 0.76/0.97, with 30° sectors. The sensitivity of the grid method was significantly higher than that of the other methods (P < 0.001), whereas the specificity was not. Coefficients of variation and interclass correlation coefficients of intervisit measurements of averaged RNFLT over each 0.21 × 0.21-mm grid were 3.1% to 11.3% and 0.937 to 0.760, respectively, in a separate OAG patient group. CONCLUSIONS: Grid-wise analyses of peripapillary RNFLT for differentiating early-stage glaucoma showed >0.90 sensitivity and ≥0.95 specificity.

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.

Contributing factors for progression of visual field loss in normal-tension glaucoma patients with medical treatment.

PURPOSE: To investigate the prognostic factors responsible for the progression of visual field defects (VFDs) in patients with normal-tension glaucoma (NTG) treated with topical antiglaucoma medications. PATIENTS AND METHODS: A total of 92 eyes in 92 NTG patients treated with only topical antiglaucoma medications for ≥ 5 years were retrospectively analyzed. To identify subfield-based prognostic factors, the central 30-degree visual field (Humphrey Field Analyzer) was divided into 6 subfields: upper and lower arcuate, paracentral, and cecocentral subfields. Factors related to subfield-based progression (age, refraction, mean intraocular pressure (IOP), IOP variability, central corneal thickness, and disc hemorrhage) were evaluated using a linear mixed model. RESULTS: Ninety-two eyes in 92 NTG patients were included in this study. The mean observation period was 7.7 ± 2.7 (5.0 to 15.5) years, and the estimated rate of change in the mean deviation value was -0.16 ± 0.31 dB/y (P<0.001). A subfield-based linear mixed model analysis of the time course of changes in the mean of total deviation identified a greater extent of myopia as a significant positive prognostic factor for VFD progression in the upper paracentral area (P=0.016). The mean IOP, central corneal thickness, disc hemorrhage, age, and IOP variation showed no significant contribution in any of the subfields. CONCLUSIONS: The extent of myopia was found to be a significant positive prognostic factor for VFD progression in the upper paracentral subfield for non-high-myopic NTG eyes with an average IOP of 14.2 mm Hg under topical antiglaucoma medication.

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.