Developing an Item Bank to Measure Quality of Life in Individuals With Glaucoma, and the Results of the Interview With Patients: The Effect of Visual Function, Visual Field Progression Rate, Medical, and Surgical Treatments on Quality of Life.

PURPOSE: To construct a new item bank to measure quality of life (QOL) in glaucoma patients and to evaluate glaucoma patients' QOL using the item bank. METHODS: An item bank of questions was generated through a literature review of QOL instruments useful for glaucoma patients. Using this item bank, a cognitive survey was performed on 203 patients with glaucoma (112 males and 91 females, 61.9±11.9 y old; mean±SD). The results were then analyzed using the Rasch analysis, and the Rasch-derived disability scores were predicted using linear modelling and the following clinical parameters: age, mean total deviation (mTD) in superior and inferior visual field (mTDsup/mTDinf), mTD progression rate, better visual acuity, worse visual acuity, number of eye drops administered per day, number of trabeculectomy procedures experienced in both eyes. RESULTS: A total of 23 questionnaires of QOL in glaucoma patients were identified resulting in an item bank of 187 questions related to the following tasks: reading/writing, walking, going out, eating and driving (direct disability) as well as questions concerned with worry/anxiety, social participation, and physical symptoms (indirect disability). In the optimal model for direct disability, age and mTDinf were identified as significant predictors, whereas number of eye drops administered per day and number of trabeculectomy experienced were included in the optimal model for indirect disability. CONCLUSIONS: A new item bank to measure QOL in glaucoma patients was developed and evaluated. Age and mTDinf were found to be related to direct disability while medical and surgical treatments were related to indirect disability.

Estimating the Binocular Visual Field of Glaucoma Patients With an Adjustment for Ocular Dominance.

PURPOSE: To investigate whether it is possible to improve estimation of the binocular visual field (VF) using monocular sensitivities on a linear scale adjusted for ocular dominance. METHODS: Monocular and binocular VF measurements were evaluated using the Humphrey Field Analyzer (HFA; 24-2 Swedish Interactive Threshold Algorithm standard program) in 60 eyes of 30 patients with open angle glaucoma. Ocular dominance was measured twice in each patient and the average value was used. Measured binocular sensitivity was then predicted based on monocular measurements using the "better sensitivity" integrated visual field (IVF) method, monocular sensitivity summation methods on the dB scale, linear scale (1/Lambert), and finally monocular sensitivity summation methods on the linear scale adjusted for the ocular dominance. RESULTS: The absolute prediction error with the linear scale summation method (mean ± SD: 3.11 ± 4.00) was significantly smaller than the IVF method (3.15 ± 4.09; P = 0.014). Further, the absolute prediction error for the ocular dominance adjusted method (3.10 ± 3.99) was significantly smaller than the nonadjusted linear scale summation method (P = 0.014). The absolute prediction error associated with the dB scale summation method was significantly larger than any other method (8.15 ± 5.06; P < 0.0001). CONCLUSIONS: The most accurate estimation of binocular sensitivity was achieved using the linear monocular sensitivity summation model adjusted for ocular dominance.

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.

Estimating the Usefulness of Humphrey Perimetry Gaze Tracking for Evaluating Structure-Function Relationship in Glaucoma.

PURPOSE: We have previously reported that fixation loss (FL) rates, false-positive (FP) rates, and gaze tracking (GT) parameters (average tracking failure frequency per stimulus [TFF], average blinking frequency [BF], average frequency of eye movements between 1° and 2° [move1-2], between 3° and 5° [move3-5], and equal to or more than 6° [move≥6]) are related to the over- or underestimation of visual field (VF) results. The purpose of the current study was to validate these results by investigating the effect of implementing the GT parameters on the relationship between VF results and optical coherence tomography (OCT) measurements. METHODS: Two hundred forty-four eyes of 155 open-angle glaucoma patients were included. Vision fixation during VF tests with the Humphrey Field Analyzer (24-2 SITA standard) was evaluated using the gaze fixation chart at the bottom of the VF printout. Mean total deviation (mTD) values were calculated, and their relationship with OCT-determined circumpapillary retinal nerve fiber layer (cp-RNFL), OCT-determined macular ganglion cell complex (GCC) thickness, and axial length was investigated using the corrected Akaike Information Criterion (AICc) in linear mixed modeling. RESULTS: In the best model, average total cpRNFL thickness, average total GCC thickness, axial length, FL, FP, move3-5, move≥6, TFF, and BF were selected as significant predictors (mTD = 2.1 + 0.097 × average total cpRNFL thickness + 0.089 × average total GCC thickness - 0.94 × axial length + 2.7 × FL + 7.2 × FP - 7.0 × move3-5 - 1.8 × move≥6 - 4.2 × TFF - 1.7 × BF). CONCLUSIONS: Both GT parameters and classic VF reliability indices had significant influence on the structure-function relationship analysis in 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.

Clustering visual field test points based on rates of progression to improve the prediction of future damage.

PURPOSE: To develop new visual field (VF) sectors based on pointwise rates of glaucomatous VF progression ("progression regions") and to evaluate their usefulness for predicting future progression. METHODS: A training dataset consisting of 10 VFs from each of 412 eyes in 412 open-angle glaucoma patients and a validation dataset consisting of 15 VFs from each of 71 eyes in 45 patients were investigated. First, using the training dataset, the VF was divided into small regions, according to the rates of progression of all 52 test points in the VF. Then, using the initial four VFs of the validation dataset, total deviation (TD) values in the 10th VF were predicted by applying linear regression analysis in derived regions and the absolute prediction error was calculated. The analysis was iterated, predicting TD values of the 10th VF, but each time including an additional VF in the regression (from five to nine VFs). Absolute prediction errors were then compared with conventional pointwise linear regression (PLR) and regression based on Nouri-Mahdavi (NM) sectors. RESULTS: Twenty-three progression regions were derived. In general, absolute prediction errors were significantly smaller for regression based on these regions compared with PLR and NM sectors. CONCLUSIONS: Predictions of VF progression can be improved by dividing the VF into small regions based on clusters of test points with similar progression rates.

Discriminating between glaucoma and normal eyes using optical coherence tomography and the 'Random Forests' classifier.

PURPOSE: To diagnose glaucoma based on spectral domain optical coherence tomography (SD-OCT) measurements using the 'Random Forests' method. METHODS: SD-OCT was conducted in 126 eyes of 126 open angle glaucoma (OAG) patients and 84 eyes of 84 normal subjects. The Random Forests method was then applied to discriminate between glaucoma and normal eyes using 151 OCT parameters including thickness measurements of circumpapillary retinal nerve fiber layer (cpRNFL), the macular RNFL (mRNFL) and the ganglion cell layer-inner plexiform layer combined (GCIPL). The area under the receiver operating characteristic curve (AROC) was calculated using the Random Forests method adopting leave-one-out cross validation. For comparison, AROCs were calculated based on each one of the 151 OCT parameters. RESULTS: The AROC obtained with the Random Forests method was 98.5% [95% Confidence interval (CI): 97.1-99.9%], which was significantly larger than the AROCs derived from any single OCT parameter (maxima were: 92.8 [CI: 89.4-96.2] %, 94.3 [CI: 91.1-97.6] % and 91.8 [CI: 88.2-95.4] % for cpRNFL-, mRNFL- and GCIPL-related parameters, respectively; P<0.05, DeLong's method with Holm's correction for multiple comparisons). The partial AROC above specificity of 80%, for the Random Forests method was equal to 18.5 [CI: 16.8-19.6] %, which was also significantly larger than the AROCs of any single OCT parameter (P<0.05, Bootstrap method with Holm's correction for multiple comparisons). CONCLUSIONS: The Random Forests method, analyzing multiple SD-OCT parameters concurrently, significantly improves the diagnosis of glaucoma compared with using any single SD-OCT measurement.

Validating the sumi quality of life questionnaire with rasch analysis.

PURPOSE: To validate the Sumi Visual Disability Questionnaire (Sumi VDQ) to estimate visual disability in glaucoma patients using Rasch analysis. METHODS: A total of 162 glaucoma patients underwent visual field (VF) testing in both eyes (Humphrey 24-2 Swedish Interactive Threshold Algorithm [SITA] standard program). The binocular VF was then calculated using the integrated VF (IVF) method. Visual disability was scored using the Sumi VDQ, which was originally written in Japanese and contains 30 items (questions). Response scale analysis, targeting, and infit statistics associated with Rasch analysis were evaluated. Unidimensionality was analyzed using principal component analysis (PCA). In addition, the correlation between the person parameter obtained with Rasch analysis and the mean of total deviation values (mTD) in the IVF was compared with the correlation between the arithmetic sum of visual disability score and mTD of the IVF. RESULTS: All 30 items in the Sumi VDQ showed productive infit values (0.61-1.46). The person parameters distributed between -4.50 and 3.62, while the item difficulty targeting parameters distributed between -0.88 and 2.06. None of the PCA components had eigenvalues whose lower limit of 95% confidence interval (CI) exceeded 2 (0-1.5). There was a significant relationship between person parameter and mTD of IVF (r = -0.78, P < 0.001), which was significantly stronger (Meng-Rosenthal-Rubin method, P = 0.002) than that between arithmetic sum of visual disability score and mTD of IVF (r = -0.61, P < 0.001). CONCLUSIONS: The Sumi VDQ has constructive psychometric properties. In particular, the Rasch analysis-derived person parameter appears to be clinically more meaningful than the arithmetic sum of visual disability score.

Evaluation of various machine learning methods to predict vision-related quality of life from visual field data and visual acuity in patients with glaucoma.

BACKGROUND/AIMS: We investigated whether it was useful to use machine learning algorithms to predict patients' vision related quality of life (VRQoL) from visual field (VF) and visual acuity (VA). METHODS: VRQoL was surveyed in 164 glaucomatous patients using the Sumi questionnaire. Their VRQoL score was predicted using machine learning algorithms (Random Forest, gradient boosting, support vector machine) based on total deviation (TD) values from integrated VF (IVF), VA, age and gender. For comparison, VRQoL score was predicted using standard linear regression with mean of IVF, TD values, and VA, and also the stepwise model selection by Akaike Information Criterion. Prediction error was calculated as root mean of the squared prediction error (RMSE) associated with the leave one out cross validation. RESULTS: RMSEs associated with general VRQoL score were smaller for the machine learning algorithms (1.99 to 2.21) compared with the standard linear model and the stepwise model selection (2.35 to 3.20). A similar tendency was found in each individual VRQoL task score. CONCLUSIONS: We found that it was advantageous to use machine learning methods to predict VRQoL accurately. These statistical methods could be used to help clinicians better understand patients' VRQoL without the need for extra tests other than standard VA and VF.

Impact of better and worse eye damage on quality of life in advanced glaucoma.

The purpose of the study was to investigate the influence of VF and the VA on vision related quality of life (VRQoL) in advanced glaucoma. Subjects consist of 50 glaucoma patients with mean deviation (MD) less than -20 dB in at least one eye. Patients' VRQoL was assessed using the 'Sumi questionnaire'. The impact of seven visual measures on VRQoL were compared using principal component regression: MDs of better and worse eyes with 10-2 and 24-2 Humphrey VFs, LogMAR VAs of better and worse eyes and the Esterman score. The root mean of the squared prediction error (RMSE) was calculated using leave-one-out cross validation. Better eye summary measurements were much more influential on VRQoL than corresponding worse eye measurements and Esterman score in every VRQoL task. In conclusion, in advanced glaucoma, VF parameters of the better eye are important for the VRQoL of the patient.

Detection of progression of glaucomatous visual field damage using the point-wise method with the binomial test.

PURPOSE: To compare the performance of newly proposed point-wise linear regression (PLR) with the binomial test (binomial PLR) against mean deviation (MD) trend analysis and permutation analyses of PLR (PoPLR), in detecting global visual field (VF) progression in glaucoma. METHODS: 15 VFs (Humphrey Field Analyzer, SITA standard, 24-2) were collected from 96 eyes of 59 open angle glaucoma patients (6.0 ± 1.5 [mean ± standard deviation] years). Using the total deviation of each point on the 2(nd) to 16(th) VFs (VF2-16), linear regression analysis was carried out. The numbers of VF test points with a significant trend at various probability levels (p<0.025, 0.05, 0.075 and 0.1) were investigated with the binomial test (one-side). A VF series was defined as "significant" if the median p-value from the binomial test was <0.025. Similarly, the progression analysis was carried out using only second to sixth VFs (VF2-6). The performance of each method was evaluated using the 'consistency measures'; proportion both significant (PBS): both VF series (VF2-6 and VF2-16) were "significant", proportion both were not significant (PBNS): both were "not significant", proportion inconsistently significant (PIS): VF2-16 was "not significant" but VF2-6 was "significant". A similar analysis was carried out using VF2-7 and VF2-15 series, and the performance was compared with MD trend analysis and PoPLR. RESULTS: The PBS of the binomial PLR method (0.14 to 0.86) was significantly higher than MD trend analysis (0.04 to 0.89) and PoPLR (0.09 to 0.93). The PIS of the proposed method (0.0 to 0.17) was significantly lower than the MD approach (0.0 to 0.67) and PoPLR (0.07 to 0.33). The PBNS of the three approaches were not significantly different. CONCLUSIONS: The binomial BLR method gives more consistent results than MD trend analysis and PoPLR, hence it will be helpful as a tool to 'flag' possible VF deterioration.

Cross-sectional study: Does combining optical coherence tomography measurements using the 'Random Forest' decision tree classifier improve the prediction of the presence of perimetric deterioration in glaucoma suspects?

OBJECTIVES: To develop a classifier to predict the presence of visual field (VF) deterioration in glaucoma suspects based on optical coherence tomography (OCT) measurements using the machine learning method known as the 'Random Forest' algorithm. DESIGN: Case-control study. PARTICIPANTS: 293 eyes of 179 participants with open angle glaucoma (OAG) or suspected OAG. INTERVENTIONS: Spectral domain OCT (Topcon 3D OCT-2000) and perimetry (Humphrey Field Analyser, 24-2 or 30-2 SITA standard) measurements were conducted in all of the participants. VF damage (Ocular Hypertension Treatment Study criteria (2002)) was used as a 'gold-standard' to classify glaucomatous eyes. The 'Random Forest' method was then used to analyse the relationship between the presence/absence of glaucomatous VF damage and the following variables: age, gender, right or left eye, axial length plus 237 different OCT measurements. MAIN OUTCOME MEASURES: The area under the receiver operating characteristic curve (AROC) was then derived using the probability of glaucoma as suggested by the proportion of votes in the Random Forest classifier. For comparison, five AROCs were derived based on: (1) macular retinal nerve fibre layer (m-RNFL) alone; (2) circumpapillary (cp-RNFL) alone; (3) ganglion cell layer and inner plexiform layer (GCL+IPL) alone; (4) rim area alone and (5) a decision tree method using the same variables as the Random Forest algorithm. RESULTS: The AROC from the combined Random Forest classifier (0.90) was significantly larger than the AROCs based on individual measurements of m-RNFL (0.86), cp-RNFL (0.77), GCL+IPL (0.80), rim area (0.78) and the decision tree method (0.75; p<0.05). CONCLUSIONS: Evaluating OCT measurements using the Random Forest method provides an accurate prediction of the presence of perimetric deterioration in glaucoma suspects.

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.

Identifying areas of the visual field important for quality of life in patients with glaucoma.

PURPOSE: The purpose of this study was to create a vision-related quality of life (VRQoL) prediction system to identify visual field (VF) test points associated with decreased VRQoL in patients with glaucoma. METHOD: VRQoL score was surveyed in 164 patients with glaucoma using the 'Sumi questionnaire'. A binocular VF was created from monocular VFs by using the integrated VF (IVF) method. VRQoL score was predicted using the 'Random Forest' method, based on visual acuity (VA) of better and worse eyes (better-eye and worse-eye VA) and total deviation (TD) values from the IVF. For comparison, VRQoL scores were regressed (linear regression) against: (i) mean of TD (IVF MD); (ii) better-eye VA; (iii) worse-eye VA; and (iv) IVF MD and better- and worse-eye VAs. The rank of importance of IVF test points was identified using the Random Forest method. RESULTS: The root mean of squared prediction error associated with the Random Forest method (0.30 to 1.97) was significantly smaller than those with linear regression models (0.34 to 3.38, p<0.05, ten-fold cross validation test). Worse-eye VA was the most important variable in all VRQoL tasks. In general, important VF test points were concentrated along the horizontal meridian. Particular areas of the IVF were important for different tasks: peripheral superior and inferior areas in the left hemifield for the 'letters and sentences' task, peripheral, mid-peripheral and para-central inferior regions for the 'walking' task, the peripheral superior region for the 'going out' task, and a broad scattered area across the IVF for the 'dining' task. CONCLUSION: The VRQoL prediction model with the Random Forest method enables clinicians to better understand patients' VRQoL based on standard clinical measurements of VA and VF.

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.

Peripapillary retinal nerve fiber layer thickness determined by spectral-domain optical coherence tomography in ophthalmologically normal eyes.

OBJECTIVES: To evaluate the peripapillary distribution of retinal nerve fiber layer thickness (RNFLT) in normal eyes using spectral-domain optical coherence tomography and to study potentially related factors. METHODS: In 7 institutes in Japan, RNFLT in 7 concentric peripapillary circles with diameters ranging from 2.2 to 4.0 mm were measured using spectral-domain optical coherence tomography in 251 ophthalmologically normal subjects. Multiple regression analysis for the association of RNFLT with sex, age, axial length, and disc area was performed. RESULTS: Retinal nerve fiber layer thickness decreased linearly from 125 to 89 µm as the measurement diameter increased (P < .001, mixed linear model). Retinal nerve fiber layer thickness correlated with age in all diameters (partial correlation coefficient [PCC] = -0.40 to -0.32; P < .001) and negatively correlated with disc area in the 2 innermost circles but positively correlated in the 3 outermost circles (PCC = -0.30 to -0.22 and 0.17 to 0.20; P ≤ .005). Sex and axial length did not correlate with RNFLT (P > .08). The decay slope was smallest in the temporal and largest in the nasal and inferior quadrants (P < .001); positively correlated with disc area (PCC = 0.13 to 0.51; P ≤ .04); and negatively correlated with RNFLT (PCC = -0.51 to -0.15; P ≤ .01). CONCLUSIONS: In normal Japanese eyes, RNFLT significantly correlated with age and disc area, but not with sex or axial length. Retinal nerve fiber layer thickness decreased linearly as the measurement diameter increased. The decay slope of RNFLT was steepest in the nasal and inferior quadrants and steeper in eyes with increased RNFLT or smaller optic discs.

Ultrasound biomicroscopy in narrow peripheral anterior chamber eyes with or without peripheral anterior synechiae.

AIM: To compare the configurations of the anterior ocular segment including the anterior chamber (AC) angle and ciliary body between eyes with a narrow AC angle (ACA) with and without peripheral anterior synechiae (PAS). PATIENTS AND METHODS: One hundred and one eyes of 101 consecutive patients with a temporal peripheral AC depth one-quarter of the corneal thickness or less were included. Gonioscopy and ultrasound biomicroscopy were performed under light and dark conditions. The existence of PAS was further confirmed with compression gonioscopy with indentation. Eyes with findings suggestive of plateau iris configuration or those with glaucomatous optic neuropathy were carefully excluded. The biometric parameters including the ACA, the angle opening distance at 500 mum, the trabecular-ciliary process distance, the iris-zonule distance, and the scleral-ciliary process angle were determined. RESULTS: PAS were found in 43 (43%) of the 101 eyes. There were no differences in age, refractive error, or intraocular pressure between PAS-positive and PAS-negative eyes (P>0.1). ACA, iris-zonule distance, scleral-ciliary process angle under light and/or dark conditions were significantly smaller in the PAS-positive eyes than in the PAS-negative eyes (P<0.05). CONCLUSIONS: Shallow peripheral AC depth and relatively anteriorly located ciliary body was significantly associated with the presence of PAS in eyes with a narrow ACA.

Indocyanine green and trypan blue: intracellular uptake and extracellular binding by human retinal pigment epithelial cells.

PURPOSE: To examine the intracellular uptake and extracellular binding of indocyanine green (ICG) and trypan blue (TB) by human retinal pigment epithelium (RPE) cells in vitro at clinically relevant concentrations. METHODS: Human RPE cells (ARPE19 cells) were exposed to 0.01%, 0.05%, and 0.25% ICG or 0.06%, 0.15%, and 0.25% TB for 15 seconds, 30 seconds, and 5 minutes, and the dye concentrations taken up by the cells were evaluated by spectrophotometric analysis. RESULTS: ICG was significantly taken up by ARPE19 cells after exposure to 0.05% for 5 minutes, 0.01% for 30 seconds, and 0.25% ICG for 15 seconds, whereas TB was not taken up by RPE cells under the conditions in this study. CONCLUSION: ICG is bound and taken up by RPE cells at concentrations lower than clinically used, and TB is not. Understanding the effects of dyes on ocular tissues leads to more effective and safer dye-assisted vitrectomy protocols, although the experimental setting is different from the clinical situation.