Risk factors for glaucoma are reflected in abnormal responses to frequency-doubling technology screening in both normal and glaucoma eyes.

The frequency-doubling technology (FDT) screening test (FDT-C-20-1) has adopted in many recent population-based glaucoma surveys, but factors associated with false-positive (FP) responses to FDT-C-20-1 in normal eyes and false-negative (FN) responses in glaucoma eyes were not known. These factors were investigated in a population-based setting using the data from 3805 normal eyes (2381 subjects) and 272 eyes with definite glaucoma (215 subjects) in the Kumejima Study participants with reliable FDT-C-20-1 results. Considering the presence of at least one abnormal test point (P < 0.01) as abnormal, the specificity and sensitivity of FDT-C-20-1 for glaucoma were 91.8% (95% confidence interval, 91.1 ~ 92.5) and 56.3% (47.0 ~ 62.5), respectively. Multivariate linear mixed-model logistic regression analysis showed correlations with older age, worse visual acuity, greater ß-peripapillary area (P < 0.001 for all comparisons) and more myopic refraction (P = 0.030) with the FP responses in normal eyes, and normal-tension glaucoma (P = 0.043), a better mean deviation value of Humphrey perimetry (P = 0.001), larger rim area (P = 0.041), and absence of disc hemorrhage (P = 0.015) with the FN responses in glaucoma eyes. In a population-based setting, abnormal responses to FDT-C-20-1 indicate the presence of a risk factor for glaucoma in normal eyes and risk factors for more rapid progression in glaucoma eyes.

Effects of optic nerve head-related parameters on retinal vessel calibers measurement results on fundus photographs.

BACKGROUND: Although relationship between the retinal vessel caliber (RVC) and glaucoma is well known, there has been a paucity of information on the effects of glaucoma-related optic nerve head (ONH) structural factors on the RVC. Information on this relationship should be useful in studying possible roles of ocular circulation in the development and progression of glaucoma. METHOD: Subjects were from Kumejima Study participants aged 40 years and older in Kumejima, Japan. Normal subjects and eyes were defined according to standardized systemic and ocular examinations. The central retinal artery and vein equivalents (CRAE and CRVE) were determined on fundus photographs by correcting the magnification using the refractive error, corneal curvature, and axial length (AL) of an individual eye and paraxial ray tracing; the ONH structural parameters were determined by planimetry. RESULTS: In a total of 558 right eyes (558 normal subjects), aged 49.0 ± 7.1 (standard deviation) years with gradable photographs and planimetric results, CRAE averaged 136.1 ± 12.3 µm and CRVE 216.9 ± 17.4 µm. After adjustment for the effects of confounding factors in multivariate analysis, the AL (P < 0.001), rim area (P = 0.019), disc area (P = 0.042), and smoking (P = 0.035-0.043) correlated positively, and the mean blood pressure (P < 0.001) negatively with CRAE; the AL (P < 0.001), rim area (P = 0.001), disc area (P = 0.005), smoking (P < 0.001), and male sex (P = 0.013) correlated positively, and the ß-peripapillary atrophy (ß-PPA) area (P = 0.044), vertical Cup/Disc ratio (v-C/D) (P = 0.035), and age (P < 0.001) negatively with CRVE. CONCLUSION: The current study showed significant effects of rim area, v-C/D or ß-PPA area determined on the photographs on the RVC measurement results. Further, it showed a necessity to incorporate the glaucoma-related ONH structural parameters as co-variables to correctly estimate the effects of various factors on the RVC.

The Inferior, Superior, Temporal Rim Width Pattern (IST Rule) Detects Glaucoma in a Japanese Population.

PRCIS: The inferior>superior>temporal rim width rate (IST pattern) rather than inferior≥superior≥nasal≥temporal (ISNT) pattern was suited for screening glaucoma in Japanese subjects. Failure of the IST pattern was associated with several important risk factors for glaucoma. PURPOSE: The purpose of this study was to find a rim width rate pattern to yield the highest positive likelihood ratio (LR+) in detecting glaucoma eyes and to identify risk factors for glaucoma correlating with its failure in a population-based setting. METHODS: Disc stereophotographs of 2474 eyes of 2474 normal subjects and 237 eyes of 237 glaucoma subjects found in the Kumejima Study were analyzed using computer-assisted planimetry. Among all combinations of the inferior (I), superior (S), nasal (N) and/or temporal (T) rim width rate, a pattern showing the highest LR+ was selected and risk factors for glaucoma correlating with its failure were determined using multiple logistic regression analysis. RESULTS: The average I, S, N, and T rim widths (SD) were 0.45 (0.10), 0.39 (0.09), 0.47 (0.11), and 0.27 (0.07) mm. Among all combinations, the I>S>T rim width rate pattern (IST pattern) disregarding the N rim width showed the highest LR+ of 2.002 (95% confidence interval, 1.778-2.253). Failure of the IST pattern in normal eyes correlated with a smaller disc area (P<0.001) and disc ovality (P=0.005) and larger ß-peripapillary area (P<0.001) and compliance with in glaucoma eyes with a smaller ß-PPA area (P=0.027), thicker central corneal thickness (P=0.017), lower intraocular pressure (P=0.019), and higher body mass index (P=0.037). CONCLUSION: Among all combinations, the I>S>T rim width pattern, the IST pattern, yielded the highest LR+ in detecting glaucoma in Japanese glaucoma eyes and its failure of or compliance with the pattern significantly correlated with several known risk factors for glaucoma.

Relationship between ocular risk factors for glaucoma and optic disc rim in normal eyes.

AIM: To study relationships between reported risk factors for glaucoma and neuroretinal rim area in normal eyes. METHODS: The Kumejima study participants, 3762 of the 4632 eligible Kumejima residents 40 years and older, underwent a detailed ocular examination including sequential disc stereo photography. In a randomly chosen eye of a subject whose both eyes met the inclusion criteria, fundus photographs of 2474 ophthalmologically normal eyes of the 2474 subjects were analysed by computer-assisted planimetry to measure the disc, rim and ß-peripapillary atrophy (PPA) areas. The rim was divided into the superior and inferior halves by a line connecting the fovea and disc centre. RESULTS: The disc, superior and inferior halves rim and ß-PPA areas averaged 2.53±0.50 (SD), 0.82±0.15, 0.84±0.16 and 0.45±0.66 mm2. After adjustment for other systemic and ocular factors including age, disc and ß-PPA areas, disc-fovea distance (p=0.013, 0.016) correlated positively and intraocular pressure (IOP) (p=0.004, 0.006) and axial length (AL) (p<0.000, 0.004) negatively with the superior and inferior halves rim area, respectively; central corneal thickness (CCT) (p=0.008) and mean blood pressure (mBP) (p=0.020) correlated positively and male gender (p=0.012) negatively only with the superior half rims. CONCLUSIONS: Besides previously reported risk factors for glaucoma such as age or IOP, thinner CCT, lower mBP and male gender were newly found to significantly correlate with smaller rim area only in the superior half disc, and a greater disc-fovea distance with greater superior and inferior half rim areas in normal adult eyes.

Optic disc, rim and peripapillary chorioretinal atrophy in normal Japanese eyes: the Kumejima Study.

PURPOSE: To report reference data for optic disc, neuroretinal rim and ß-peripapillary atrophy (ß-PPA) in normal Japanese. METHODS: In the Kumejima study, all participants underwent disc stereo-photography; 2208 normal subjects had good-quality disc stereo and ß-PPA photographs OU. The disc and rim area and the area and angular extent of ß-PPA were evaluated by computer-assisted planimetry. RESULTS: The disc, rim, and ß-PPA area and its angular extent OD (OS) averaged 2.54 ± 0.50 (2.53 ± 0.49), 1.67 ± 0.29 (1.67 ± 0.30), 0.47 ± 0.66 (0.42 ± 0.59) mm2, and 99 ± 85 (92 ± 82) degrees (mean ± standard deviation) with bilateral Pearson's correlation coefficient of 0.890, 0.769, 0.679 and 0.632 (P < 0.001), respectively, while the 95th percentiles of the absolute inter-eye differences were 0.48, 0.41, 0.96 mm2, and 153°. The correlation coefficient between ß-PPA area and its angular extent was 0.963 (P < 0.001). Age showed negative correlation with the rim area and positive correlation with ß-PPA area (P < 0.001). Among ocular factors, disc area showed positive correlation and intraocular pressure negative correlation with the rim area (P ≤ 0.001), axial length and disc area positive correlation with ß-PPA area (P < 0.001 and P = 0.051). CONCLUSIONS: The averages and distribution of the optic disc and rim area, ß-PPA area and its angular extent in normal Japanese are reported, which will facilitate screening of glaucoma in Japanese. In normal Japanese eyes, the disc size and intraocular pressure significantly correlated with the rim area, and the axial length with ß-PPA area.

Combining multiple HRT parameters using the 'Random Forests' method improves the diagnostic accuracy of glaucoma in emmetropic and highly myopic eyes.

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 (-1.0 to +1.0 diopters [D], 63 and 59 subjects, respectively) and highly myopic eyes (-10.0 to -5.0 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.

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.

Planimetrically determined vertical cup/disc and rim width/disc diameter ratios and related factors.

PURPOSE: To evaluate the distribution and factors related to planimetrically determined vertical cup/disc (v-C/D) and rim width/disc diameter (Rw/Dd) ratios of the optic discs in a population-based study of Japanese subjects without glaucoma. METHODS: Of 4632 eligible residents 40 years of age and older, 3762 residents underwent a detailed ocular examination including sequential optic disc stereo photography with a digital nonmydriatic fundus camera. The photographs were assessed by computer-assisted planimetry. The authors studied both eyes of 2311 nonglaucomatous subjects and only one right (left) eye of 196 (175) subjects for whom disc stereo photographs were of acceptable quality. RESULTS: The median (2.5th and/or 97.5th percentile) disc area, v-C/D, its asymmetry, and the superior- and inferior-minimal Rw/Dd ratios were 2.56 (1.68, 3.71) mm(2), 0.56 (0.70), 0.05 (0.14), 0.18 (0.10), and 0.21 (0.12), respectively. Multiple regression analysis showed that males had larger discs and superior Rw/Dd and smaller inferior Rw/Dd ratios. Increased age was correlated with increased v-C/D and decreased superior and inferior Rw/Dd ratios. Higher intraocular pressure (IOP) and thinner central corneal thickness (CCT) were correlated with higher v-C/D and smaller inferior rim/disc ratios, and lower diastolic ocular perfusion pressure (OPP) with greater v-C/D and smaller superior Rw/Dd ratios. CONCLUSIONS: In nonglaucomatous eyes, increased v-C/D and decreased superior and inferior Rw/Dd ratios were significantly correlated not only with increased age and disc size but also with higher IOP, lower diastolic OPP, and thinner CCT, suggesting that these simple disc parameters also represent vulnerability to glaucoma insults in nonglaucomatous eyes.

Correlation of disc morphology quantified on stereophotographs to results by Heidelberg Retina Tomograph II, GDx variable corneal compensation, and visual field tests.

PURPOSE: Quantification of disc morphology by computer-assisted planimetry on stereophotographs and to compare the results with those by other fundus structure imaging devices and visual field tests. DESIGN: Cross-sectional study. PARTICIPANTS: Fifteen normal eyes of 15 normal subjects and 69 glaucomatous eyes of 69 open-angle glaucoma patients. METHODS: Sequential digital stereophotographs of the optic discs were obtained by a nonmydriatic fundus camera. Intraobserver reproducibility for the 3 repeated traces and interobserver reproducibility for the three individual examiners were determined. The obtained results were correlated to those by Heidelberg Retina Tomograph (HRT) II, GDx with variable corneal compensation (VCC) and visual field tests obtained within 2 months of the photography. MAIN OUTCOME MEASURES: Optic disc parameters such as disc area, cup area, rim/disc area ratio, vertical cup diameter/disc diameter (Cd/Dd) ratio and rim width/disc diameter (Rw/Dd) ratio at radial arbitrary angles. Interclass correlation coefficients (ICC) and coefficients of variance (CV) for the optic disc parameters and their correlation with HRT II, GDx VCC, and visual field test results. RESULTS: Intra- and interobserver ICC and CV were 0.88 to 0.99, 1.1% to 9.6%, and 0.72 to 0.98, 2.2% to 11.9% for area parameters, 0.81 to 0.92, 2.4% to 4.0% and 0.71 to 0.78, 4.3% to 5.0% for Cd/Dd ratio, and 0.73 to 0.91, 9.2% to 23.0% and 0.65 to 0.82, 16.9% to 27.2% for Rw/Dd ratios, respectively. Significant correlation was seen between disc and cup area and the corresponding parameters by HRT II (r(s) > 0.81; P<0.001), as well as between vertical Cd/Dd ratio and global TSNIT average by GDx VCC and visual field test indices (|r(s)| > 0.51; P<0.001), and between superior and inferior Rw/Dd ratio and their corresponding sectoral HRT II, GDx VCC and visual field test indices (r(s) > 0.31; P<0.006), respectively. Correlation with visual field test indices was comparable among stereophotographs, HRT II, and GDx VCC parameters. CONCLUSIONS: Optic disc morphologic parameters quantified on stereophotographs by our software showed satisfactory reproducibility and good correlation with those measured by other fundus structure imaging devices and visual field test results, indicating its clinical usefulness, especially in the mass screening of glaucoma.

Sensitivity and specificity of the Heidelberg Retina Tomograph II Version 3.0 in a population-based study: the Tajimi Study.

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

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

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

Laser scanning tomography of optic discs of the normal Japanese population in a population-based setting.

OBJECTIVE: To evaluate the optic disc characteristics using the Heidelberg retina tomograph (HRT) II in a large sample of normal Japanese subjects. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 3576 eyes of 2036 normal subjects, with good-quality HRT II images, of 6042 eyes of 3021 subjects aged 40 years or more who participated in the Tajimi Study, a population-based eye study in Japan. METHODS: Optic disc parameters were obtained using HRT II, and the association of gender, age, height, weight, blood pressure, ocular perfusion pressure, refraction, intraocular pressure (IOP), central corneal thickness (CCT), and disc size on HRT parameters was assessed using simple and multiple regression analyses. MAIN OUTCOME MEASURES: HRT parameters, including disc area, cup area, rim area, cup-to-disc area ratio, cup volume, rim volume, mean cup depth, maximum cup depth, height variation contour, cup shape measure, mean retinal nerve fiber layer (RNFL) thickness, and RNFL cross-sectional area, and the crude and partial correlations of the potential confounders with the HRT parameters. RESULTS: Disc area, cup-to-disc area ratio, and rim area averaged 2.06+/-0.41 mm(2) (mean+/-standard deviation), 0.23+/-0.13, and 1.55+/-0.29 mm(2), respectively. All HRT parameters were strongly or moderately correlated between right and left eyes (Pearson's correlation coefficients = 0.45-0.83, P<0.001). Absolute inter-eye differences in several HRT parameters were positively correlated with disc area (P<0.05). Multiple regression analyses adjusting for the confounders showed weak but significant correlations of height, refractive error, IOP, and CCT with several HRT parameters (partial correlation coefficient (absolute value) = 0.04-0.16, P<0.05), and moderate or weak but significant correlations of disc area with all HRT parameters (partial correlation coefficient [absolute value] = 0.05-0.73, P<0.05). Gender, weight, blood pressure, and ocular perfusion pressure did not significantly correlate with HRT parameters. CONCLUSIONS: This report presents reference data of normality for the HRT parameters based on a large sample of normal Japanese subjects. There were small but significant influences of height, refractive error, IOP, and CCT on several HRT parameters. Many HRT parameters were moderately or weakly affected by disc size. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.