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Purpose: To determine the ability of ophthalmologists across Europe to match stereoscopic optic disc photographs to visual fields of varying severity., Design: Evaluation and comparison of 2 diagnostic tests., Participants: A total of 109 of 260 invited ophthalmologists in 11 European countries. These had participated in the previous European Optic Disc Assessment Trial (EODAT), a trial on glaucoma diagnostic accuracy based on optic discs only., Methods: Each participant matched stereo optic disc photographs of 40 healthy and 48 glaucomatous eyes to a visual field chosen from 4 options per disc. The 4 presented visual fields included the corresponding one and 3 other visual fields, varying in severity. The matching accuracy and any inaccuracy per disease severity were calculated. Classification accuracy (as glaucomatous or healthy) was compared with EODAT data. Duplicate slides allowed for the assessment of intraobserver agreement., Main Outcome Measures: Accuracy of matching optic discs with their corresponding visual field and of classifying them as healthy or glaucomatous; intraobserver agreement (κ)., Results: The overall accuracy of ophthalmologists for correctly matching stereoscopic optic disc photographs to their visual fields was 58.7%. When incorrectly matched, the observers generally overestimated the visual field severity (P<0.001), notably in eyes with early glaucoma. The intraobserver agreement was, on average, moderate (0.52)., Conclusions: European ophthalmologists correctly matched stereoscopic optic disc photographs to their corresponding visual field in only approximately 59% of cases. In most mismatches, the clinicians overestimated the visual field damage., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: Genome-wide association studies have revealed new insights into the genetic determinants of open-angle glaucoma (OAG). This study was performed to determine to what extent variants within established genes (MYOC, OPTN, and WDR36) and newly identified common genetic variants (ATOH7, CDKN2B, and SIX1) contribute to the risk of OAG., Design: Population-based setting, family-based setting, and a case-control study., Participants: The Rotterdam Study I cohort (N = 5312; mean age±standard deviation [SD], 68.0±8.4 years). Findings were replicated in the Genetic Research in Isolated Populations combined with the Erasmus Rucphen Family study (N = 1750; mean age±SD, 48.3±15.2 years), and a cohort from Southampton (N = 702; mean age±SD, 72.5±10.7 years)., Methods: After identifying common variants associated with OAG within the established genes, the risk of OAG was analyzed using logistic regression. Discriminative accuracy was assessed by comparing the area under the receiver operator characteristic curve (AUC) for models, including the number of risk alleles, intraocular pressure, age, and gender, with the AUC for the same model but without the risk alleles., Main Outcome Measures: Odds ratios and AUCs of individual and combined risk alleles., Results: No consistent significant associations for the established genes (MYOC, OPTN, and WDR36) with OAG were found. However, when comparing the load of risk variants between cases and controls, 2 of 3 studies showed a significant increased risk of OAG for participants carrying more risk alleles of the 3 established genes. When combining all 6 genes, participants carrying a high number of risk alleles (highest tertile) had a 2.29-fold to 3.19-fold increase in risk of OAG compared with those carrying only a few risk alleles. The addition of the newly identified genes to IOP, age, and gender resulted in a higher AUC compared with the AUC without the newly identified genes (P = 0.027)., Conclusions: A significant contribution to the risk of OAG was found for the new common variants identified by recent genome-wide association studies, but not for variants within the established genes. Participants carrying a high number of risk alleles had an approximately 3-fold increase in the risk of OAG compared with those with a low number of risk alleles., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the diagnostic accuracy of judging optic disc photographs for glaucoma by ophthalmologists., Design: Evaluation of diagnostic test and technology., Participants: A total of 243 of 875 invited ophthalmologists in 11 European countries., Methods: We determined how well each participant classified 40 healthy eyes and 48 glaucomatous eyes with varying severity of the disease on stereoscopic slides. Duplicate slides were provided for determining intraobserver agreement. All eyes were also imaged with the GDx with variable corneal compensation (GDx-VCC) (Carl Zeiss Meditec AG, Jena, Germany) and the Heidelberg Retina Tomograph (HRT) I (Heidelberg Engineering GmbH, Heidelberg, Germany). Diagnostic accuracies of clinicians were compared with those of the best machine classifiers., Main Outcome Measures: Accuracy of classification, expressed as sensitivity, specificity, and overall accuracy. Intraobserver agreement (kappa)., Results: The overall diagnostic accuracy of ophthalmologists was 80.5% (standard deviation [SD], 6.8; range, 61.4%-94.3%). The machine classifiers outperformed most observers in diagnostic accuracy; the GDx-VCC nerve fiber indicator and the HRT's best classifier correctly classified 93.2% and 89.8% of eyes, respectively. The intraobserver agreement (kappa) varied between -0.13 and 1.0 and was on average good (0.7)., Conclusions: In general, ophthalmologists classify optic disc photographs moderately well for detecting glaucoma. There is, however, large variability in diagnostic accuracy among and agreement within clinicians. Common imaging devices outperform most clinicians in classifying optic discs., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Short-wavelength automated perimetry (SWAP) has been claimed to predict conversion to glaucoma 3 to 4 years before standard automated perimetry (SAP) defects occur. This study compared the moment of glaucomatous conversion between SWAP and SAP., Design: Prospective, longitudinal follow-up study., Participants: Four hundred sixteen subjects with ocular hypertension (intraocular pressure >/=22 and

Purpose: To compare the diagnostic accuracy of scanning laser polarimetry (SLP) parameters between images taken with enhanced corneal compensation (ECC) and those with variable corneal compensation (VCC) and to explore the effect of atypical birefringence patterns on this accuracy., Design: Cross-sectional observational study., Participants: Forty-one healthy subjects and 92 patients with primary open-angle glaucoma., Methods: Variable corneal compensation and ECC images were obtained of 1 eye per subject, selected randomly if both eyes were eligible. For both ECC and VCC, the areas under the receiver operating characteristic curves (AUROCs) and the sensitivity at a specificity of > or =95% were calculated per parameter in all eyes. The analyses were reperformed separately in eyes with and without atypical birefringence patterns (ABP) images., Main Outcome Measures: The AUROCs and sensitivities at a specificity of > or =95% for various SLP parameters in all eyes and in eyes without ABP images., Results: The diagnostic accuracy for most standard parameters (temporal-superior-nasal-inferior-temporal [TSNIT] average, superior average, inferior average, and TSNIT standard deviation) in all eyes was statistically significantly higher with ECC than with VCC, except for the nerve fiber indicator (NFI). When only eyes without ABP were used for the analysis, the diagnostic accuracy of SLP parameters with VCC improved, and the differences in diagnostic accuracy between ECC and VCC for these parameters lost their statistical significance., Conclusions: Standard SLP parameters (except for the NFI) generally had a higher diagnostic accuracy when eyes were imaged with ECC than with VCC because there were fewer ABP images with ECC than with VCC. Enhanced corneal compensation therefore may be more reliable than VCC for the detection of glaucoma. A future automated classifier, similar to the current NFI, may perform better if it is trained on data obtained with ECC. Clinically, retinal nerve fiber layer images with marked ABP, acquired with either ECC or VCC, should be viewed with caution.

Purpose: To compare scanning laser polarimetry (SLP) measurements of retinal nerve fiber layer (RNFL) thickness in perimetrically unaffected eyes of glaucoma patients with those in their fellow eyes with field loss and eyes of healthy subjects., Design: Observational case-control study., Participants and Controls: Twenty-three glaucoma patients with a reproducible visual field (VF) defect in one eye (mean mean deviation [MD], -5.71 decibels [dB]) and a normal VF in the other one (i.e., < or =1 VF test point below the 5% probability level [mean MD, -0.01 dB]) and 73 control eyes of as many age-matched healthy subjects (mean MD, 0.39 dB). The MDs and pattern standard deviations of the glaucoma patients' eyes with normal VFs and the control eyes did not statistically significantly differ (independent samples t test, P = 0.15 and P = 0.61, respectively)., Methods: All subjects were measured in both eyes with the GDxVCC, a commercially available instrument featuring SLP with automated variable corneal compensation. Standard automated perimetry was assessed by means of the Humphrey Field Analyzer (24-2 Full Threshold or Swedish interactive threshold algorithm Standard achromatic test program)., Main Outcome Measures: The standard GDxVCC parameters TSNIT (temporal, superior, nasal, inferior, temporal) Average, Superior Average, Inferior Average, TSNIT Std. Dev., and Nerve Fiber Indicator (NFI) were determined. We also assessed the thickness values in 6 parapapillary sectors. In addition, we calculated the proportion of eyes per group with an NFI of > or =40., Results: GDxVCC measurements showed more RNFL thinning in the perimetrically unaffected eyes of glaucoma patients than in the healthy control eyes. The RNFL in the perimetrically unaffected eyes of glaucoma patients was thicker than that in their fellow eyes with field loss. The NFI had a value of > or =40 in 11 of 23 (47.8%) perimetrically unaffected eyes of glaucoma patients, 19 of 23 (82.6%) eyes with VF loss of glaucoma patients, and 3 of 73 (4.1%) healthy control eyes., Conclusion: With the GDxVCC, thinning of the RNFL may be detected in perimetrically unaffected eyes of glaucoma patients with field loss in their fellow eyes.

Purpose: To determine the diagnostic accuracy of the GDx VCC in the diagnosis of glaucoma., Design: Prospective, comparative, observational, clinic-based case series., Participants: One eye each of 77 healthy subjects and 162 patients with primary open-angle glaucoma of Caucasian racial origin. Healthy subjects had normal visual fields (VFs), healthy-looking optic discs, and intraocular pressures of < or =21 mmHg in both eyes. Glaucoma patients had a reproducible glaucomatous VF defect and a glaucomatous appearance of the optic disc in at least one eye., Methods: All subjects were measured with the GDx VCC with an automated variable corneal compensator. We constructed receiver operating characteristic (ROC) curves for all available parameters. Subsequently, we calculated sensitivity, specificity, and multilevel likelihood ratios for the best discriminating parameter in the entire group. In addition, we calculated sensitivity and specificity in patients with mild, moderate, and severe glaucomatous damage separately., Main Outcome Measures: Software-derived parameters TSNIT (temporal, superior, nasal, inferior, temporal) Average, Superior Average, Inferior Average, TSNIT Std. Dev. (standard deviation), and Nerve Fiber Indicator (NFI)., Results: The areas under the ROC curve for TSNIT Average, Superior Average, Inferior Average, TSNIT Std. Dev., and NFI were 0.93, 0.94, 0.90, 0.92, and 0.98, respectively. For the best discriminating parameter NFI, the sensitivity and specificity with a cutoff point of > or =40 were 89.0% and 95.9%, respectively. The multilevel likelihood ratios for glaucoma were 0.07 at NFI values of <35, 1.30 at values between 35 and 44, and 61.50 at values of > or =44. At the cutoff level of > or =40, the sensitivities of the NFI for correctly identifying glaucoma patients with mild, moderate, and severe damage were 83.8%, 92.9%, and 90.1%, respectively., Conclusions: The GDx VCC allowed easy, rapid, and accurate discrimination between healthy and glaucomatous eyes. The NFI was the best discriminating parameter. The GDx VCC seems to fulfill criteria for a glaucoma screening device.

Purpose: The presently available scanning laser polarimeter (SLP) has a fixed corneal compensator (FCC) that neutralizes corneal birefringence only in eyes with birefringence that matches the population mode. A prototype variable corneal compensator (VCC) provides neutralization of individual corneal birefringence based on individual macular retardation patterns. The aim of this study was to evaluate the relative ability of the SLP with the FCC and with the VCC to discriminate between normal and glaucomatous eyes., Design: Prospective, nonrandomized, comparative case series., Participants: Algorithm-generating set consisting of 56 normal eyes and 55 glaucomatous eyes and an independent data set consisting of 83 normal eyes and 56 glaucomatous eyes., Testing: Sixteen retardation measurements were obtained with the SLP with the FCC and the VCC from all subjects., Main Outcome Measures: Dependency of parameters on age, gender, ethnic origin, and eye side was sought. Logistic regression was used to evaluate how well the various parameters could detect glaucoma. Discriminant functions were generated, and the area under the receiver operating characteristic (ROC) curve was determined., Results: Discrimination between normal and glaucomatous eyes on the basis of single parameters was significantly better with the VCC than with the FCC for 6 retardation parameters: nasal average (P = 0.0003), superior maximum (P = 0.0003), ellipse average (P = 0.002), average thickness (P = 0.003), superior average (P = 0.010), and inferior average (P = 0.010). Discriminant analysis identified the optimal combination of parameters for the FCC and for the VCC. When the discriminant functions were applied to the independent data set, areas under the ROC curve were 0.84 for the FCC and 0.90 for the VCC (P<0.021). When the discriminant functions were applied to a subset of patients with early visual field loss, areas under the ROC curve were 0.82 for the FCC and 0.90 for the VCC (P<0.016)., Conclusion: Individual correction for corneal birefringence with the VCC significantly improved the ability of the SLP to distinguish between normal and glaucomatous eyes and enabled detection of patients with early glaucoma.

Purpose: To compare the visualization of localized retinal nerve fiber layer (RNFL) defects in GDx images with fixed and with individualized compensation of anterior segment birefringence (FC and IC, respectively) with their visualization in red-free fundus photographs., Design: Observational case series., Participants: Eight eyes of six glaucoma patients with localized, wedge-shaped RNFL defects in red-free fundus photographs with matching visual field defects., Methods: We imaged all eyes with a GDx equipped with a variable corneal compensator (VCC). The VCC replaced the standard fixed compensator and could be set to compensate for birefringence of up to 120 nm at any axis. Individual anterior segment birefringence was estimated from a macular retardation profile that resulted from the interaction between birefringence of the anterior segment and that of Henle's fiber layer. Measurements of RNFL retardation were made with the GDx with FC (60 nm of retardation with a slow axis of 15 degrees nasally downward) and with IC. Maps of retardation measurements with FC and IC were superimposed on red-free fundus photographs., Main Outcome Measures: Visualization of localized RNFL defects., Results: Localized RNFL defects were visible in GDx retardation maps obtained with IC. The defects closely matched those observed in red-free fundus photographs. With FC, however, the GDx retardation images did not correlate well with red-free fundus photography., Conclusions: An individualized anterior segment compensation in the GDx improves the visualization of localized glaucomatous loss.

Purpose: The GDx (Laser Diagnostic Technologies, San Diego, CA) is a scanning laser polarimeter that measures retardation to assess retinal nerve fiber layer thickness in vivo. Eye movements during image acquisition may result in motion artifacts in the GDx image. The aims of this study were to investigate the effect of motion artifacts on the retardation values and to illustrate how motion artifacts can be identified., Design: Observational case series., Participants: Thirty-two normal subjects and 28 glaucoma patients participated., Methods: We imaged all 60 subjects with the GDx. Images with identified motion artifacts were compared with images without motion artifacts from the same eye and the same session. In 25 cases, the artifact was identified in the superior segment only, and the effect on the superior maximum parameter was calculated. In 26 cases, the artifact was observed in the inferior segment only, and the effect on the inferior maximum parameter was calculated. In nine cases, the artifact was observed superiorly and inferiorly, and the effect on both parameters was calculated. In all 60 cases, the effect on The Number (a summary parameter) was calculated. We also analyzed the groups of glaucoma patients and normal subjects separately., Main Outcome Measures: Superior maximum parameter, inferior maximum parameter, The Number parameters., Results: In general, the identified motion artifacts led to an increase in retardation, reflected by an increase in the superior maximum and inferior maximum parameter by 5.9 micro m and 3.4 micro m, respectively (P < 0.001). The Number decreased by 3.4 with motion artifacts (P = 0.001). The variability of this effect was large. In one case, the motion artifact increased retardation by as much as 28.6 micro m. The effect of motion artifacts was greater in glaucoma patients than in normal subjects., Conclusions: The identified motion artifacts generally increase retardation values. This increase, however, is highly variable. Therefore, images with such motion artifacts should be viewed with caution or excluded from analysis.

Purpose: To compare optic nerve head (ONH) surface change detection by confocal scanning laser tomography (CSLT) within the LSU Experimental Glaucoma (LEG) study to expert clinicians viewing the LEG stereophotographs., Design: Experimental study., Participants: Four fellowship-trained glaucoma specialists., Methods: In the LEG study, six 15 CSLT images (TopSS, Laser Diagnostics Technologies, San Diego, CA) and four 2x optic disc stereophotographs were obtained from both eyes of 12 monkeys on 3 separate days and then every 2 weeks after laser to one eye (study eye) to elevate intraocular pressure. ONH surface change detection within the CSLT images is described in our companion report. In this report, the preliminary study compared change detection by the CSLT multivariate strategy with that of a single clinician viewing stereophotograph pairs on three separate occasions as the "gold standard." The main study compared change detection by three additional clinicians viewing a subset of LEG stereophotograph pairs on three separate occasions with that of the CSLT multivariate strategy as the "gold standard." Clinician change detection was assessed for partial (two of three occasions) or complete (three of three occasions) agreement. Three comparison groups within the main study are emphasized: 44 group A comparisons assessed false-positive change detection (specificity); 38 group B comparisons assessed change detection within 38 instances (11 onset and 27 progression events) of CSLT-detected study eye change; and 30 group C comparisons assessed change detection within 30 instances in which the CSLT failed to detect change in study eyes., Main Outcome Measures: Clinician change detection within each comparison with either partial or complete agreement., Results: Within the main study, intrareading (-.29 to 0.67) and interreading (0.24--0.56) session agreement for each clinician was slight to moderate by kappa test. Good specificity (less than 10% false-positive change detection) was achieved within the 44 group A comparisons by two of the three clinicians, but only when the more stringent criterion (change detection on three of three occasions) was applied. Of the 38 group B comparisons (in which the CSLT detected change), the two clinicians who achieved good specificity in group A failed to detect change in 25 and 16 instances, respectively, using the more stringent (three of three) criterion. Similarly, of the 30 group C comparisons (in which the CSLT failed to detect change), these two clinicians detected change in three and seven instances, respectively, but in only one comparison did they both detect change., Conclusions: This study provides the first direct evidence that an existing CSLT may reasonably meet or exceed the ONH surface change detection performance of fellowship-trained glaucoma specialists in at least those eyes with good CSLT reproducibility.

Purpose: The GDx (Laser Diagnostic Technologies, San Diego, CA) is a scanning laser polarimeter designed to assess the peripapillary nerve fiber layer in vivo. On the GDx, a nerve fiber bundle can appear as a single or as a split bundle. The aim of our study was to determine the prevalence of split nerve fiber layer bundles and to demonstrate their clinical relevance., Design: Cross-sectional study., Participants: Two hundred fifty-four healthy volunteers participated., Methods: We imaged 454 eyes of 254 healthy white persons with the GDx. All eyes had intraocular pressure of 21 mmHg or less, normal appearance of the optic nerve head, and normal visual fields (Humphrey Field Analyzer 24-2 full threshold program). According to our working definition, a bundle appeared 'split' when the color-coded pixels corresponding to areas of higher retardation were clearly divided into two more-or-less symmetrical parts not resembling a wedge defect. The classification was performed by two independent observers who used an identical set of reference examples to standardize the classification., Main Outcome Measures: The presence of a split nerve fiber layer bundle., Results: Interobserver agreement was very good (kappa = 0.83), and a consensus was reached in all cases. In 419 eyes (92.3%) there was no split bundle. A split superior bundle was seen in 29 eyes (6.4%). A split inferior bundle was observed in five eyes (1.1%), and in one eye (0.2%) a split bundle was seen superiorly and inferiorly. When considering subjects, a split superior bundle (either in the right eye, or in the left eye, or in both eyes) occurred in 12.0% of normal subjects. The 'superior maximum' parameter was significantly lower in eyes with a split superior bundle than in eyes with a single superior bundle (67.2 microm vs. 89.9 microm; P<0.001). The same was observed for the 'symmetry' parameter (0.88 microm vs. 0.98 microm; P<0.001)., Conclusions: Split nerve fiber layer bundles are a common finding in healthy eyes when imaged with the GDx. A split superior bundle is the most frequent variation, in which cases an abnormal superior maximum or symmetry parameter, otherwise potential indicators of glaucoma, should not readily be interpreted as abnormal.

Purpose: To compare artificial eye amplitudes in patients who randomly received either a hydroxyapatite or an acrylic, scleral-covered spherical implant after enucleation., Design: Randomized, controlled trial., Participants: Thirty-four consecutive patients who underwent enucleation because of an intraocular melanoma and 21 healthy control participants from the hospital staff., Methods: Eligible patients randomly received a hydroxyapatite or an acrylic, scleral-covered spherical orbital implant. Fourteen patients were fitted with a hydroxyapatite implant, and 16 were fitted with an acrylic implant. We measured horizontal and vertical saccadic amplitudes of both the artificial eye and the healthy eye. Measurements were performed with the magnetic search coils technique. Saccadic amplitudes of the artificial eye were compared with the healthy eye of the patient. The amplitudes of the healthy eyes were compared with saccadic amplitudes of control participants. The interval from surgery to measurements was at least 3 months in all patients. Saccadic gain (artificial eye and eye amplitude divided by target amplitude) and saccadic symmetry (artificial eye amplitude divided by healthy eye amplitude) were calculated., Main Outcome Measures: Saccadic gain and saccadic symmetry., Results: The gain in the healthy eyes of the patients was comparable with the gain of the control eyes. Saccadic symmetry was 1.0 in control participants. In patients, it was 0.334 in horizontal saccades and 0.577 in vertical saccades. However, saccadic symmetry did not differ significantly between the acrylic group and the hydroxyapatite group (P: > 0.1 for any saccadic direction). Equivalence was detectable with a power more than 90% for horizontal saccades and more than 80% for vertical saccades. Curvilinearity was rejected for both patient groups and for all saccadic directions (P: > 0.5)., Conclusions: When no motility peg is placed, acrylic and hydroxyapatite spherical implants yield comparable saccadic amplitudes of the artificial eye. Artificial eye amplitudes were markedly more restricted horizontally than vertically. In all saccadic directions, the relation between target amplitude and artificial eye amplitude was linear.

Purpose: This study aimed to obtain normal nerve fiber layer (NFL) measurements by means of scanning laser polarimetry in black subjects and to compare these measurements with those in normal white subjects., Methods: Polarimetric NFL measurements were obtained in 1 eye of 133 normal black subjects and 133 age- and gender-matched white subjects. Ratios were determined for the superior and inferior NFL, each relative to the nasal value (S/N and I/N, respectively). Results of black and white subjects were compared by means of the Student's t test. The effect of age on NFL measurements was determined with linear regression analysis., Results: The mean S/N was statistically significantly lower in black subjects (1.7) when compared with that of white subjects (2.5). Similar values were obtained for I/N. In this cross-sectionally performed study, a negative, albeit not significant relation (-0.003) was recognized between NFL measurements and age for both S/N and I/N in black subjects. In the white subjects, there was a statistically significant relation of -0.012 between age and NFL measurements., Conclusions: The NFL retardation is less in black than in white subjects. Compared with white subjects, the decrease in NFL measurements of black subjects over time, cross sectionally, appears less.

Purpose: The authors attempt to establish a relation between hard contact lens wear and upper eyelid ptosis., Methods: This study consists of two parts. In the first part, the authors compare the unilateral or bilateral ptosis that developed during hard contact lens wear in 17 patients with the involutional ptosis that developed in another group of 73 patients. In the second part, the authors compare both upper and lower eyelid position in 46 patients who had been wearing hard contact lenses for at least 10 years with the position of 50 matched controls who had never worn contact lenses., Results: The ptosis that had developed in the 17 patients who wore hard contact lenses was clinically similar to that caused by involutional levator disinsertion. The second part of the study shows that the prolonged wearers of hard contact lenses had upper eyelids that were lower by approximately 0.5 mm when compared with control subjects. This difference is statistically significant. According to standard criteria, there were at least 10 ptotic eyelids in the contact lens group versus 1 in the control group., Conclusion: The study findings suggest that prolonged hard contact lens wear may induce a lower position of the upper eyelid and eventually lead to ptosis through levator disinsertion.