Disc Stereophotographs Research Articles

Combining Structural and Functional Measurements to Improve Detection of Glaucoma Progression using Bayesian Hierarchical Models

To present and evaluate a new methodology for combining longitudinal information from structural and functional tests to improve detection of glaucoma progression and estimation of rates of change. This observational cohort study included 434 eyes of 257 participants observed for an average of 4.2 ± 1.1 years and recruited from the Diagnostic Innovations in Glaucoma Study (DIGS). The subjects were examined annually with standard automated perimetry, optic disc stereophotographs, and scanning laser polarimetry with enhanced corneal compensation. Rates of change over time were measured using the visual field index (VFI) and average retinal nerve fiber layer thickness (TSNIT average). A bayesian hierarchical model was built to integrate information from the longitudinal measures and classify individual eyes as progressing or not. Estimates of sensitivity and specificity of the bayesian method were compared with those obtained by the conventional approach of ordinary least-squares (OLS) regression. The bayesian method identified a significantly higher proportion of the 405 glaucomatous and suspect eyes as having progressed when compared with the OLS method (22.7% vs. 12.8%; P < 0.001), while having the same specificity of 100% in 29 healthy eyes. In addition, the bayesian method identified a significantly higher proportion of eyes with progression by optic disc stereophotographs compared with the OLS method (74% vs. 37%; P = 0.001). A bayesian hierarchical modeling approach for combining functional and structural tests performed significantly better than the OLS method for detection of glaucoma progression. (ClinicalTrials.gov number, NCT00221897.).

Beta-zone parapapillary atrophy and multifocal visual evoked potentials in eyes with glaucomatous optic neuropathy

We investigated changes in multifocal visual evoked potential (mfVEP) responses due to beta-zone parapapillary atrophy (ßPPA). Patients with glaucomatous optic neuropathy (GON) with or without standard achromatic perimetry (SAP) abnormalities were referred for mfVEP testing during a 2-year period. Eyes with good quality optic disc stereophotographs and reliable SAP results were included. The mfVEP monocular mean latency delays (ms) and amplitudes (SNR) were analyzed. Age, SAP mean deviation (MD), pattern standard deviation (PSD), and spherical equivalent (SE) were analyzed in the multivariate model. Generalized estimated equations were used for comparisons between groups after adjusting for inter-eye associations. Of 394 eyes of 200 patients, 223 (57%) had ßPPA. The ßPPA eyes were older (59.6±13.7 vs. 56.5±13.7year, P=0.02), more myopic (-4.0±3.5 vs. -1.3±3.5 D, P<0.01), and had poorer SAP scores (MD: -4.9±5.2 vs. -2.6±5.2dB, P<0.01; PSD: 4.3±2.9 vs. 2.5±3.0dB, P<0.01). By univariate analysis, mean latencies were longer in ßPPA eyes (6.1±5.3 vs. 4.0±5.5ms, P<0.01). After adjusting for differences in SE, age, and SAP MD, there was no significant difference between the two groups (P=0.09). ßPPA eyes had lower amplitude log SNR (0.49±0.16 vs. 0.56±0.15, P<0.01), which lost significance (P=0.51) after adjusting for MD and PSD. Although eyes with ßPPA had significantly lower amplitudes and prolonged latencies than eyes without ßPPA, these differences were attributable to differences in SAP severity, age, and refractive error. Thus, ßPPA does not appear to be an independent factor affecting mfVEP responses in eyes with GON.

β-Zone Parapapillary Atrophy and the Rate of Retinal Nerve Fiber Layer Thinning in Glaucoma

To evaluate whether β-zone parapapillary atrophy (PPA) is associated with the rate of retinal nerve fiber layer (RNFL) thickness change as assessed by trend-based analysis using time-domain optical coherence tomography (OCT). This retrospective cohort study included 202 glaucomatous eyes that were observed for ≥3 years with serial OCTs and stereo disc photographs. Subjects were divided into two groups according to the presence (n = 144) or absence of β-zone PPA (n = 58). The rates of progressive thinning in global, quadrant, and clock-hour OCT RNFL thicknesses were determined using linear regression and compared between groups. Logistic regression analysis was used to determine the factors associated with the rate of global RNFL thinning. The mean rate for global RNFL thinning over time was -1.03 ± 1.50 μm/year. Eyes with β-zone PPA showed a significantly faster rate of RNFL thinning than did eyes without β-zone PPA in the inferior quadrant and 7 o'clock sector (values of P < 0.0029). Multivariate analysis showed significant influence of the presence of β-zone PPA and the percentage increase in the PPA to disc area ratio during the follow-up on the rate of OCT RNFL thinning (odds ratio [OR], 3.314, P = 0.007; OR, 2.894, P = 0.003, respectively). Glaucomatous eyes with β-zone PPA are at increased risk for progressive RNFL thinning.

Is the ataxia of Charlevoix–Saguenay a developmental disease?

The autosomal recessive spastic ataxia of Charlevoix–Saguenay (ARSACS) is considered a neurodegenerative disease caused by mutations in the SACS gene, located on chromosome 13q12.12. It is a syndrome that comprises skeletal, retinal and neurological manifestations, among which feature spasticity, cerebellar ataxia and peripheral neuropathy.Five patients with a molecular diagnosis of ARSACS underwent clinical, radiological, and ophthalmologic examinations. Every one of the identified causal mutations was novel. Spastic ataxia, peripheral neuropathy, pes cavus, and hammertoes were found in every case. T2 and T2-fluid attenuation inversion recovery-weighted MRI sequences demonstrated cerebellar atrophy and a hypointense linear striation at the pons. Tensor diffusion sequences revealed that the hypointense striation corresponded with hyperplasia of the pontocerebellar fibres, which gave place to abnormally thick middle cerebellar peduncles. Stereophotographs of the optic discs showed an increased number of retinal fibres, and ocular coherence tomography, increased thickness of the retinal nerve fibre layer. The authors suggest that the hyperplasic pontocerebellar fibres compress the pyramidal tracts at the pons since a very early stage of central nervous system development, causing spasticity, and may also cause cerebellar atrophy by means of glutamate-induced excitotoxicity. The abnormal amount of retinal fibres traversing the optic discs could have caused the detected mild peripheral visual field defects.Taken together, these facts point to a developmental cause in ARSACS, as it does not exhibit the tissue atrophy characteristic of degenerative diseases. Clinical deterioration in ARSACS seems to be mediated by phenomena (compression of the pyramidal tracts and cerebellar glutamate-mediated excitotoxicity) derived from the developmental anomalies referred to, while the neuromuscular symptoms are caused by a peripheral neuropathy with pathologic features suggestive of a similar origin. These observations should be taken into account when research about the origin of ARSACS is undertaken.

Three-dimensional Nature of Retinal Nerve Fiber Layer Defects

To demonstrate the 3-dimensional nature of wedge-shaped retinal nerve fiber layer (RNFL) losses. To study the impact of training glaucoma fellows in this identification technique by evaluating their rate of RNFL loss detection on stereo disc photographs. Wedge-shaped RNFL defects were identified in stereo disc photographs of early-glaucoma patients. The 3-dimensional nature of RNFL defects and overlying retinal blood vessel contour changes were identified. Four glaucoma fellows were given stereophotographs to identify the presence or absence of RNFL defects. After training in identification of RNFL defects by noting their 3-dimensional nature and overlying blood vessel contour changes, the same set of photographs were reevaluated by the fellows. We determined whether there was a difference between the before and after assessments in the probability of a correct response for each of the fellows. Loss of retinal thickness in the form of grooves and the resulting 3-dimensional nature of the RNFL defects were visualized on stereoscopic examination. Overlying retinal blood vessels coursed into and out of the RNFL defects. Three case examples of such wedge-shaped RNFL defects are presented. For each fellow, the proportion of RNFL defects correctly identified after training was greater than the proportion before training (P<0.001). Identifying the 3-dimensional nature of wedge-shaped RNFL defects may improve rate of detection of RNFL defects during clinical examination.

Vascular Retinal, Neuroimaging and Ultrasonographic Markers of Lacunar Infarcts

Lacunar infarcts may be caused by macro- or microvascular disease due to several mechanisms. This study aims to demonstrate that retinal vascular disturbances in patients with lacunar infarcts associated with neuroimaging and ultrasound markers can help to identify small-vessel disease. Prospective ambulatory study of patients with ischaemic stroke and a control group. A retinographic study was performed by 20° bilateral optic disc stereophotography and 50° bilateral optic fundus retinography. Microangiopathy was evaluated as the presence of nonparenchymal vascular affectation and retinopathy as at least one retinal disturbance. Ultrasonographic study evaluated carotid disorder parameters and the mean pulsatility index. The MRI protocol included T1-weighted, T2-weighted, DP-weighted and FLAIR. We included 156 nonlacunar infarcts, 39 lacunar infarcts and 50 controls. Microangiopathy was more frequent in hypertensive (62·6% vs. 35·7%, P<0·0001) and vascular retinopathy in diabetic patients (11·7% vs. 3·8%, P=0·039). Microangiopathy (97·4% vs. 41·1%, P<0·0001) and leukoaraiosis (94·4% vs. 50·3%, P<0·0001) were more frequent and the mean pulsatility index was higher (1·9 ± 0·2 vs. 1·4 ± 0·5, P<0·0001) in patients with lacunar infarcts. Lacunar infarcts were independently associated with microangiopathy (odds ratio 12·81, 95% CI 1·52-107·86), the mean pulsatility index (odds ratio 8·13, 95% CI 1·17-56·20) and leukoaraiosis (odds ratio 3·45, 95% CI 1·09-10·93). The presence of leukoaraiosis plus microangiopathy was associated with lacunar infarcts with odds ratio 21·31 (95% CI 8·74-51·93). The association of retinal microangiopathy (but not vascular retinopathy) and leukoaraiosis is linked to small-vessel disease and may be a useful marker of lacunar infarcts not secondary to a macrovascular lesion.

A geometric morphometric assessment of the optic cup in glaucoma

The morphologic appearance of the optic disc is of interest in glaucoma. In contrast to descriptive classification systems that are currently used, a quantitative approach to the analysis of optic disc morphology is required. Our goal was to determine the optimal method for quantifying optic cup shape by comparing traditional (ovality, form-factor and neuroretinal rim (NRR) width ratio) and geometric morphometric approaches. Left optic disc stereophotographs of 160 (80 normal and 80 glaucomatous (stratified by severity)) subjects were examined. The optic cup margins were stereoscopically delineated with a custom tracing system and saved as a series of discrete points. The geometric morphometric methods of elliptic Fourier analysis (EFA) and sliding semi-landmark analysis (SSLA) were used to eliminate variation unrelated to shape (e.g. size) and yield a series of shape variables. Differences in optic cup shape between normal and glaucoma groups were investigated. Discriminant functions were computed and the sensitivity and specificity of each technique determined. Receiver operator characteristic (ROC) curves were calculated for all methods and evaluated in their potential to discriminate between normal and glaucomatous eyes based on the shape variables. All geometric morphometric methods revealed differences between normal and glaucomatous eyes in optic cup shape, in addition to the traditional parameters of ovality, form-factor and NRR width ratio ( p < 0.0005). SSLA (minimum bending energy criterion – 18 points) had the best sensitivity (83%) and area under the curve (AUC) (0.91). EFA (72 points) performed similarly well (74%, 0.89) as did the set of traditional shape-based variables (76%, 0.86). This study demonstrated that a geometric morphometric approach for discriminating between normal and glaucomatous eyes in optic cup shape is superior to that provided by traditional single parameter shape measures. Such analytical techniques could be incorporated into future automated optic disc screening modalities.

The Relationship between Intraocular Pressure Reduction and Rates of Progressive Visual Field Loss in Eyes with Optic Disc Hemorrhage

To evaluate rates of visual field progression in eyes with optic disc hemorrhages and the effect of intraocular pressure (IOP) reduction on these rates. Observational cohort study. The study included 510 eyes of 348 patients with glaucoma who were recruited from the Diagnostic Innovations in Glaucoma Study (DIGS) and followed for an average of 8.2 years. Eyes were followed annually with clinical examination, standard automated perimetry visual fields, and optic disc stereophotographs. The presence of optic disc hemorrhages was determined on the basis of masked evaluation of optic disc stereophotographs. Evaluation of rates of visual field change during follow-up was performed using the visual field index (VFI). The evaluation of the effect of optic disc hemorrhages on rates of visual field progression was performed using random coefficient models. Estimates of rates of change for individual eyes were obtained by best linear unbiased prediction (BLUP). During follow-up, 97 (19%) of the eyes had at least 1 episode of disc hemorrhage. The overall rate of VFI change in eyes with hemorrhages was significantly faster than in eyes without hemorrhages (-0.88%/year vs. -0.38%/year, respectively, P<0.001). The difference in rates of visual field loss pre- and post-hemorrhage was significantly related to the reduction of IOP in the post-hemorrhage period compared with the pre-hemorrhage period (r = -0.61; P<0.001). Each 1 mmHg of IOP reduction was associated with a difference of 0.31%/year in the rate of VFI change. There was a beneficial effect of treatment in slowing rates of progressive visual field loss in eyes with optic disc hemorrhage. Further research should elucidate the reasons why some patients with hemorrhages respond well to IOP reduction and others seem to continue to progress despite a significant reduction in IOP levels. Proprietary or commercial disclosure may be found after the references.

Glaucomatous Progression in Series of Stereoscopic Photographs and Heidelberg Retina Tomograph Images

To compare optic disc changes using automated analysis of Heidelberg retina tomograph (HRT) images with assessments, by glaucoma specialists, of change in stereoscopic photographs. Baseline and follow-up stereophotographs and corresponding HRT I series of 91 eyes from 56 patients were selected. The selection criteria were sufficiently long, good-quality HRT series (7 visits in > or =70 months of follow-up) and follow-up photographs contemporaneous with the final HRT image. Topographic change analysis (TCA), statistic image mapping (SIM), and linear regression of rim area (RALR) across time were applied to HRT series. Glaucomatous change determined from stereophotographs by expert observers was used as the reference standard. Expert observers identified 33 eyes (36%) as exhibiting glaucomatous change. Altering HRT progression criteria such that 36% of eyes progressed according to each method resulted in concordance between HRT methods and stereophotograph assessment of 54% for TCA, 65% for SIM, and 67% for RALR (Cohen kappa = 0.05, 0.23, and 0.30, respectively). Receiver operating characteristic curves of the HRT analyses revealed poor precision of HRT analyses to predict stereophotograph-assessed change: areas under the curve were 0.61 for TCA, 0.62 for SIM, and 0.66 for RALR. Statistical methods for detecting structural changes in HRT images exhibit only moderate agreement with each other and have poor agreement with expert-assessed change in optic disc stereophotographs.

Rates of Progressive Retinal Nerve Fiber Layer Loss in Glaucoma Measured by Scanning Laser Polarimetry

To evaluate rates of change measured with scanning laser polarimetry with enhanced corneal compensation (GDx ECC) and compare them to those measured using the variable corneal compensation (GDx VCC) method in a cohort of glaucoma patients and individuals suspected of having the disease followed over time. Observational cohort study. The study included 213 eyes of 213 patients with an average follow-up time of 4.5 years. Images were obtained annually with the GDx ECC and VCC, along with optic disc stereophotographs and standard automated perimetry (SAP) visual fields. Progression was determined by the Guided Progression Analysis software for SAP and by masked assessment of stereophotographs by expert graders. Joint linear mixed-effects models were used to evaluate rates of change in GDx measurements and their relationship with disease progression. Thirty-three patients (15%) showed progression over time on visual fields and/or stereophotographs. Mean rates of average retinal nerve fiber layer (RNFL) thickness change measured by the GDx ECC were significantly different in progressors versus nonprogressors (-1.24 microm/year vs -0.34 microm/year; P < .001). The area under the ROC curve for discriminating progressors from nonprogressors was significantly higher for rates of change measured by ECC compared to VCC (0.89 vs 0.65; P < .001). Rates of RNFL change detected by the GDx ECC were significantly greater in eyes with progressive glaucoma compared to eyes with stable disease. Also, the ECC performed significantly better than the VCC for detection of change, suggesting that it could improve longitudinal evaluation of the RNFL with scanning laser polarimetry.

Agreement for Detecting Glaucoma Progression with the GDx Guided Progression Analysis, Automated Perimetry, and Optic Disc Photography

To evaluate the ability of the GDx Variable Corneal Compensation (VCC) Guided Progression Analysis (GPA) software for detecting glaucomatous progression. Observational cohort study. The study included 453 eyes from 252 individuals followed for an average of 46+/-14 months as part of the Diagnostic Innovations in Glaucoma Study. At baseline, 29% of the eyes were classified as glaucomatous, 67% of the eyes were classified as suspects, and 5% of the eyes were classified as healthy. Images were obtained annually with the GDx VCC and analyzed for progression using the Fast Mode of the GDx GPA software. Progression using conventional methods was determined by the GPA software for standard automated achromatic perimetry (SAP) and by masked assessment of optic disc stereophotographs by expert graders. Sensitivity, specificity, and likelihood ratios (LRs) for detection of glaucoma progression using the GDx GPA were calculated with SAP and optic disc stereophotographs used as reference standards. Agreement among the different methods was reported using the AC(1) coefficient. Thirty-four of the 431 glaucoma and glaucoma suspect eyes (8%) showed progression by SAP or optic disc stereophotographs. The GDx GPA detected 17 of these eyes for a sensitivity of 50%. Fourteen eyes showed progression only by the GDx GPA with a specificity of 96%. Positive and negative LRs were 12.5 and 0.5, respectively. None of the healthy eyes showed progression by the GDx GPA, with a specificity of 100% in this group. Inter-method agreement (AC(1) coefficient and 95% confidence intervals) for non-progressing and progressing eyes was 0.96 (0.94-0.97) and 0.44 (0.28-0.61), respectively. The GDx GPA detected glaucoma progression in a significant number of cases showing progression by conventional methods, with high specificity and high positive LRs. Estimates of the accuracy for detecting progression suggest that the GDx GPA could be used to complement clinical evaluation in the detection of longitudinal change in glaucoma.

Correlation of Disc Morphology Quantified on Stereophotographs to Results by Heidelberg Retina Tomograph II, GDx Variable Corneal Compensation, and Visual Field Tests

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. Cross-sectional study. Fifteen normal eyes of 15 normal subjects and 69 glaucomatous eyes of 69 open-angle glaucoma patients. 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. 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. 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. 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.

Prediction of Functional Loss in Glaucoma From Progressive Optic Disc Damage

To evaluate the ability of progressive optic disc damage detected by assessment of longitudinal stereophotographs to predict future development of functional loss in those with suspected glaucoma. The study included 639 eyes of 407 patients with suspected glaucoma followed up for an average of 8.0 years with annual standard automated perimetry visual field and optic disc stereophotographs. All patients had normal and reliable standard automated perimetry results at baseline. Conversion to glaucoma was defined as development of 3 consecutive abnormal visual fields during follow-up. Presence of progressive optic disc damage was evaluated by grading longitudinally acquired simultaneous stereophotographs. Other predictive factors included age, intraocular pressure, central corneal thickness, pattern standard deviation, and baseline stereophotograph grading. Hazard ratios for predicting visual field loss were obtained by extended Cox models, with optic disc progression as a time-dependent covariate. Predictive accuracy was evaluated using a modified R(2) index. Progressive optic disc damage had a hazard ratio of 25.8 (95% confidence interval, 16.0-41.7) and was the most important risk factor for development of visual field loss with an R(2) of 79%. The R(2)s for other predictive factors ranged from 6% to 26%. Presence of progressive optic disc damage on stereophotographs was a highly predictive factor for future development of functional loss in glaucoma. These findings suggest the importance of careful monitoring of the optic disc appearance and a potential role for longitudinal assessment of the optic disc as an end point in clinical trials and as a reference for evaluation of diagnostic tests in glaucoma.

Detection of Glaucoma Progression with Stratus OCT Retinal Nerve Fiber Layer, Optic Nerve Head, and Macular Thickness Measurements

To evaluate and compare the ability of optical coherence tomography (OCT) retinal nerve fiber layer (RNFL), optic nerve head, and macular thickness parameters to detect progressive structural damage in glaucoma. This observational cohort study included 253 eyes of 253 patients. Images were obtained annually with the Stratus OCT (Carl Zeiss Meditec, Inc., Dublin, CA) along with optic disc stereophotographs and standard automated perimetry (SAP) visual fields. The median follow-up time was 4.01 years. Progression was determined by the Guided Progression Analysis software for SAP (Carl Zeiss Meditec, Inc.) and by masked assessment of optic disc stereophotographs performed by expert graders. Random coefficient models and receiver operating characteristic (ROC) curves were used to evaluate the relationship between change in Stratus OCT parameters over time and progression as determined by SAP and/or stereophotographs. From the 253 eyes, 31 (13%) showed progression over time by stereophotographs and/or SAP. Mean rates of change in average RNFL thickness were significantly higher for progressors compared with nonprogressors (-0.72 mum/y vs. 0.14 mum/y; P = 0.004), with sensitivity of 77% for specificity of 80%. RNFL parameters performed significantly better than ONH and macular thickness measurements in discriminating progressors from nonprogressors. The parameters with the largest ROC curve areas for each scanning area were inferior RNFL thickness (0.84), cup area (0.66), and inferior inner macula thickness (0.64). Stratus OCT RNFL parameters discriminated between eyes progressing by visual fields or optic disc photographs and eyes that remained stable by these methods and performed significantly better than ONH and macular thickness parameters in detecting change over time.

Functional correlation between retinal sensitivity threshold values of standard automated perimetry in glaucoma

Abstract Purpose To study the interrelationship among the 52 retinal sensitivity threshold values of the Humphrey visual field analyzer with the 24‐2 Swedish interactive threshold algorithm (SITA) standard strategy in glaucoma patients. Methods Prospective cross‐sectorial study. 104 eyes of 104 patients with diagnosed glaucoma by means of optic disc stereophotographs were evaluated. Each 52 threshold points of the SITA Standard 24.2 program in the standard automated perimetry (SAP) were obtained. The upper and the lower hemifield were studied separately. Pearson correlation coefficients were calculated between each of the mean threshold values at each point of the visual hemifield and the rest of the threshold points. Results Perimetric correlation maps between threshold values in the same hemifield were obtained. Most of the points had moderate and high correlations (r ≥ 0,65) with neighboring points and distant points corresponding to the retinotopic distribution of the retinal nerve fibers. Conclusion There is a functional relationship, in glaucoma patients SAP, between neighboring and distant threshold points in corresponding to the anatomical arrangement of ganglion cells axons. This enables to achieve perimetric patterns of glaucoma defects.

Patterns of progression of localized retinal nerve fibre layer defect on red-free fundus photographs in normal-tension glaucoma

To investigate patterns of progression of localized retinal nerve fibre layer (RNFL) defect on red-free fundus photographs and to quantify extents of progression in normal-tension glaucoma (NTG) patients. Sixty-five eyes of consecutive 65 NTG patients who had shown progression of localized RNFL defect on serial red-free fundus photographs were selected for this study. Patterns of progression of localized RNFL defect on red-free fundus photographs were categorized and extents of progression were quantified. Serial assessments of disc stereophotographs and visual fields were also performed to detect progression. The most common pattern of progression was widening of the defect towards the macula (n=37; 56.9%) followed by deepening of the defect (n=25; 38.5%), appearance of a new defect (n=6; 9.2%), and widening of the defect away from the macula (n=5; 7.7%). Eight eyes simultaneously showed two patterns of progression. Mean angular widening of the defect towards the macula and away from the macula was 6.4+/-4.1 degrees (range: 1.1-17.1 degrees , n=37) and 3.4+/-2.1 degrees (range: 1.1-5.2 degrees , n=5), respectively. No progression was observed on the disc stereophotographs (n=65) or in the visual fields (n=55) in 64 eyes (98.5%) and 46 eyes (83.6%), respectively. There were four patterns of progression of localized RNFL defect. In most cases, RNFL loss proceeded temporally.

Population Prevalence of Tilted and Torted Optic Discs Among an Adult Chinese Population in Singapore

To determine the prevalence of tilted and torted optic discs and associated risk factors among Chinese adults in Singapore. As part of a population-based survey, optic disc stereophotographs of both eyes were obtained, and left eyes were analyzed using imaging software. A tilted optic disc was defined as an index of tilt (ratio of minimum to maximum optic disc diameter) less than 0.75. The angle of tilt was defined as the angle between the maximum and vertical optic disc diameter, and optic discs were graded as torted if the angle of tilt exceeded 15 degrees . Twenty-six of 739 subjects (3.5%) had tilted optic discs, and 478 (64.7%) had torted optic discs. Myopia was present in 23 of 26 eyes (88.5% [95% confidence interval, 69.9%-97.6%]) with tilted optic discs and in 211 of 661 eyes (31.9% [28.4%-35.6%]) without tilted optic discs (P < .001). On multivariate analysis, myopia (spherical equivalent) was a significant risk factor for tilted optic discs (P < .001). Index of tilt was not associated with corneal astigmatism or with cylindrical refractive error. Seventeen eyes (65.4%) with tilted optic discs had an optic disc morphologic abnormality, but none were glaucomatous. The prevalence of tilted optic discs among this Chinese population was 3.5%. Tilted optic discs were associated with myopia but not with glaucoma.

Evaluating a New Disc Staging Scale for Glaucomatous Damage: The Ability to Detect Change over Time

To assess the ability of Disc Damage Likelihood Scale (DDLS) in detecting glaucomatous changes in the optic nerve on sequential optic disc stereo-photographs as compared with three other different cup/disc grading systems (C/D). Eighty-three pairs of stereo-photographs with a minimum of 5-year follow-up were examined by one group of three observers masked to chronological order by using their clinical expertise. Their conclusions were considered gold standard. Another group of three glaucoma experts examined the same masked pairs to evaluate glaucomatous changes using four different optic nerve grading systems: DDLS, vertical, horizontal, and maximal cup/disc. Ratings of these four methods in the second group were then compared with the gold standard. Baseline and follow-up photographs of 83 eyes were included. Mean follow-up was 6 years. The sensitivities for detecting glaucomatous nerve changes were 71.4%, 63.9%, 66.7%, and 47.2% for DDLS, vertical, horizontal, and maximal cup/disc, respectively. The specificity for finding nerve change was 70.9%, 51.1%, 40.4%, and 48.9%, respectively. The proportion of photographs identified as showing glaucomatous changes differed significantly between the DDLS and vertical C/D (VCD) (X2=7.900, p=0.005), between the DDLS and horizontal C/D (HCD) (X2=13.89, p=0.000), and between DDLS and maximum C/D (MCD) (X2=4.192, p=0.041). The largest area (74.4%) under the receiver operator characteristic curve was obtained by using the DDLS. DDLS had higher sensitivity and specificity for detecting glaucomatous changes versus the other three C/Ds when considering sequential stereo-photographs.

Identifying Preperimetric Functional Loss in Glaucoma: A Blue-on-Yellow Multifocal Visual Evoked Potentials Study

To determine the ability of blue-on-yellow multifocal visual evoked potentials (BonY mfVEP) to identify functional loss in preperimetric glaucoma. Prospective case series. Thirty patients with glaucomatous optic discs and normal standard visual fields. All patients underwent BonY mfVEP, dilated optic disc stereophotography, and optical coherence tomography (Fast RNFL protocol). Optic disc photographs were assessed by 2 independent examiners in a masked fashion. The mfVEP amplitude asymmetry and latency values were analyzed and compared topographically with findings of disc assessment. Average retinal nerve fiber layer (RNFL) thickness, RNFL asymmetry, and sectors with RNFL thinning were compared between patients with and without mfVEP defects. Fourteen (46.7%) patients demonstrated significant abnormality on amplitude asymmetry deviation plots of BonY mfVEP. In all 14 cases, the defect was monocular and corresponded to the eye with the worse disc. In 13 of 14 patients, the defect also corresponded to the location of the worst affected rim. Average RNFL thickness of eyes with mfVEP defects was 81.2+/-9.9 microm, significantly lower than that of patients without defects (90+/-10.5 microm; P = 0.035). Mean asymmetry of RNFL (better minus worse eye) also was significantly higher for patients with mfVEP defects compared with those without such defects (9.0+/-6.4 microm vs. 3.0+/-7 microm; P = 0.03). Average latency of both eyes of glaucomatous patients was delayed compared with that of controls, with no difference in latency between worse and better eyes of glaucoma patients. There was no association of latency delay with either the location of disc changes or mfVEP amplitude defects. Amplitude asymmetry of the BonY mfVEP seems to be a promising tool to identify functional loss in preperimetric glaucoma. Proprietary or commercial disclosure may be found after the references.

The Relationship between Intraocular Pressure and Progressive Retinal Nerve Fiber Layer Loss in Glaucoma

To evaluate the relationship between intraocular pressure (IOP) and progressive retinal nerve fiber layer (RNFL) loss, as measured by scanning laser polarimetry with enhanced corneal compensation (GDx ECC), in a cohort of glaucoma patients and individuals suspected of having the disease followed over time. Observational cohort study. The study included 344 eyes of 204 patients recruited from the Diagnostic Innovations in Glaucoma Study (DIGS). There were 98 eyes (28%) with a diagnosis of glaucoma and 246 (72%) were considered glaucoma suspects at baseline. Images were obtained annually with the GDx ECC scanning laser polarimeter, along with stereophotographs and SAP. The study included a total of 1211 GDx ECC visits with an average of 3.5 visits per eye. Progression was determined by the Guided Progression Analysis software for SAP and by masked assessment of stereophotographs performed by expert graders. Random coefficient models were used to evaluate the relationship between IOP and RNFL thickness measurements over time in progressors and nonprogressors. Models were adjusted for baseline diagnosis and central corneal thickness. For all 344 eyes, the overall rate of change for the GDx ECC average thickness at an average IOP of 17 mmHg was -0.25 microm per year (P = 0.002). Each 1-mmHg higher IOP was associated with an additional loss of 0.05 microm per year of RNFL (P = 0.001). Twenty-nine eyes (8%) showed progression on SAP and/or optic disc stereophotographs. These eyes had a significantly higher rate of RNFL change (-0.95 microm/year) than nonprogressors (-0.17 microm/year; P = 0.001). For progressors, each 1-mmHg higher IOP was associated with an additional loss of 0.13 microm per year of RNFL. Higher levels of IOP during follow-up were significantly related to higher rates of progressive RNFL loss detected by the GDx ECC. These findings suggest that the GDx ECC may be helpful in monitoring progression and estimating rates of change in patients with glaucoma or suspected of having the disease. Also, they may contribute to a better understanding of the relationship between IOP and structural deterioration in glaucoma. Proprietary or commercial disclosure may be found after the references.