Moorfields Regression Analysis Research Articles

Comparison of Diagnostic Accuracy of Heidelberg Retina Tomograph II and Heidelberg Retina Tomograph 3 to Discriminate Glaucomatous and Nonglaucomatous Eyes

To compare the diagnostic accuracy of the Moorfields regression analysis (MRA), parameters, and glaucoma probability score (GPS) from Heidelberg Retinal Tomograph (HRT) 3 (Heidelberg Engineering, Heidelberg, Germany) with MRA and parameters from HRT II in discriminating glaucomatous and healthy eyes in subjects of African and European ancestry. Case-control institutional setting. Seventy-eight glaucoma patients (44 of African ancestry, 34 of European ancestry) and 89 age-matched controls (46 of African ancestry, 33 European ancestry), defined by visual fields and self-reported race were included. Imaging was obtained with HRT II, and data were exported to a computer with the HRT 3 software using the same contour line. Area under the receiver operating characteristic (ROC) curves (AUCs), sensitivity, and specificity were evaluated for the entire group, the African ancestry group, and the European ancestry group separately. Mean disk area was compared between correctly and incorrectly diagnosed eyes by each technique. Disk, cup, and rim areas from HRT 3 were lower than HRT II (P < .0001). AUC (sensitivity at 95% specificity) was 0.85 (54%) for vertical cup-to-disk ratio (VCDR) HRT 3, 0.84 (45%) for VCDR HRT II, and 0.81 (44%) for GPS at the temporal sector. MRA HRT 3 showed greater sensitivity but lower specificity than HRT II for the entire group, the African ancestry group, and the European ancestry group. GPS classification had the lowest specificity. Glaucomatous eyes incorrectly classified by GPS had smaller mean disk area (P = .0002); control eyes incorrectly classified had greater mean disk area (P = .015). VCDR from HRT 3 showed higher sensitivity than HRT II and GPS for the entire group and for those of African ancestry and of European ancestry separately. Sensitivity of MRA improved in HRT 3 with some trade-off in specificity compared with MRA of HRT II. GPS yielded erroneous classification associated to optic disk size.

Evaluation of Optical Coherence Tomography and Heidelberg Retinal Tomography Parameters in Detecting Early and Moderate Glaucoma

To evaluate the relationship between optic nerve head (ONH) and peripapillary retinal nerve fiber layer (RNFL) parameters by optical coherence tomography (OCT) and confocal scanning laser ophthalmoscopy (Heidelberg retinal tomography; HRT; Heidelberg Engineering, Heidelberg, Germany) in early and moderate glaucoma and to compare several OCT-based automated classifiers with those inbuilt in HRT for detection of glaucomatous damage. This cross-sectional study included 60 eyes of 60 patients with glaucoma (30 early and 30 moderate visual field defects) and 60 eyes of 60 healthy subjects. All patients underwent Fast Optic Disc and Fast Peripapillary RNFL scans on the OCT and then HRT evaluation of the ONH during the same visit. Glaucoma variables obtained from OCT and HRT analyses were compared among the groups. Receiver operator characteristic (ROC) curves generated by performing linear discriminant analysis (LDA), artificial neural networks (ANNs), and classification and regression trees (CART) on OCT-based parameters were compared with the Moorfield regression analysis (MRA), R Bathija (RB), and FS Mickelberg (FSM) functions in the HRT, to classify eyes as either glaucomatous or normal. No statistically significant difference was found in the disc area measured by the OCT and HRT analyses within each study group (P > 0.05). The areas under ROC curves were 0.9822 (LDF), 0.9791 (CART), and 0.9383 (ANN) as compared with 0.859 (FSM), 0.842 (RB) and 0.767 (MRA). OCT-based automated classifiers performed better than HRT classifiers in distinguishing glaucomatous from healthy eyes. Such parameters should be integrated in the OCT to improve its diagnostic abilities.

The Effect of Levodopa and Dopamine Agonists on Optic Nerve Head in Parkinson Disease

To evaluate the effects of levodopa and dopamine agonists on retinal nerve fiber layer using scanning laser ophthalmoscope. Forty-four patients with the diagnosis of Parkinson disease and receiving levodopa or dopamine agonist monotherapy were included in this prospective study. The control group consisted of 21 normal cases. The optic nerve head images were taken with Heidelberg Retina Tomograph; rim area, rim volume, mean retinal nerve fiber layer thickness, and the results of Moorfields regression analysis were calculated. The measurement results were evaluated with Kruskal Wallis test and Mann-Whitney U-test. There was no significant difference in mean age among groups (p=0.093). Retinal nerve fiber layer was measured to be significantly decreased in cases with Parkinson disease (p=0.004) while rim area and rim volume did not show a significant change (p=0.224, p=0.804 respectively). Rim area, rim volume, and retinal nerve fiber layer were significantly greater in the group treated with levodopa while it was the thinnest in the group receiving dopamine agonists. Levodopa can have a protective affect to retinal nerve fiber layer in Parkinson disease compared to dopamine agonists.

The Effect of Disc Size and Severity of Disease on the Diagnostic Accuracy of the Heidelberg Retina Tomograph Glaucoma Probability Score

To compare the effect of disc size and disease severity on the Heidelberg Retina Tomograph (HRT) Glaucoma Probability Score (GPS) and the Moorfields Regression Analysis (MRA) for discriminating between glaucomatous and healthy eyes. Ninety-nine eyes with repeatable standard automated perimetry results showing glaucomatous damage and 62 normal eyes were included from the longitudinal Diagnostic Innovations in Glaucoma Study (DIGS). The severity of glaucomatous visual field defects ranged from early to severe (average [95% CI] pattern standard deviation [PSD] was 5.7 [5.0-6.5] dB). The GPS (HRTII ver. 3.0; Heidelberg Engineering, Heidelberg, Germany) utilizes two measures of peripapillary retinal nerve fiber layer shape (horizontal and vertical retinal nerve fiber layer curvature) and three measures of optic nerve head shape (cup depth, rim steepness, and cup size) as input into a relevance vector machine learning classifier that estimates a probability of having glaucoma. The MRA compares measured rim area with predicted rim area adjusted for disc size to categorize eyes as outside normal limits, borderline, or within normal limits. The effect of disc size and severity of disease on the diagnostic accuracy of both GPS and MRA was evaluated using the generalized estimating equation marginal logistic regression analysis. Using the manufacturers' suggested cutoffs for GPS global classification (>64% as outside normal limits), the sensitivity and specificity (95% CI) were 71.7% (62.2%-79.7%) and 82.3% (71.0%-89.8%), respectively. The sensitivity and specificity (95% CI) of the MRA result were 66.7% (58.0%-76.1%) and 88.7% (78.5%-94.34%), respectively. Likelihood ratios for regional GPS and MRA results outside normal limits ranged from 4.0 to 10.0, and 6.0 to infinity, respectively. Disc size and severity of disease were significantly associated with the sensitivity of both GPS and MRA. GPS tended to have higher sensitivities and somewhat lower specificities and lower likelihood ratios than MRA. These results suggest that in this population, GPS and MRA differentiate between glaucomatous and healthy eyes with good sensitivity and specificity. In addition, the likelihood ratios suggest that GPS may be most useful for confirming a normal disc, whereas MRA may be most helpful in confirming a suspicion of glaucoma. Larger disc size and more severe field loss were associated with improved diagnostic accuracy for both GPS and MRA.

Linear Regression Modeling of Rim Area to Discriminate Between Normal and Glaucomatous Optic Nerve Heads

To create a diagnostic algorithm by modeling the normal variability of rim area (measured by Heidelberg Retina Tomography) using linear regression in normal elderly subjects. Multiple linear regression was performed between log rim area and disc area, age, and sex in 712 normal elderly subjects. The relationship between log rim area and disc area was not linear and showed significant heteroscedascity (increasing variability of rim area with increasing disc area). These factors violate the assumptions of linear regression as performed by the Moorfields Regression Analysis (MRA), and were overcome by conducting linear regression separately for each disc area quartile. Actual rim area in each disc sector was compared with the 95% lower limit predicted by the analysis in the normal subjects and 58 glaucoma patients. Specificity and sensitivity of the New Regression Analysis (NRA) was 83% and 81%, respectively (84.4% and 82.7%, respectively for MRA). NRA specificity was unaffected by disc size (81.6% and 86.3% in the smallest and largest disc area quartiles, respectively, P=0.36). MRA specificity was reduced in larger discs (91.1% and 73.1% in smallest and largest disc area quartiles, P<0.001), with reduced sensitivity in smaller discs (58.3% and 85.0% in smallest and largest quartiles, P=0.05). Nonlinearity and heteroscedascity in the relationship between log rim area and disc area explain reduced specificity of the MRA in bigger discs as a statistical error. Although overall not offering better diagnostic performance, the NRA performed consistently across different disc sizes, offering better performance than the MRA in large discs.

Intereye Spatial Relationship of Abnormal Neuroretinal Rim Locations in Glaucoma Patients from the Diagnostic Innovations in Glaucoma Study

To determine the spatial relationship in neuroretinal rim parameter values between eyes in ocular hypertensives, glaucoma suspects, and glaucoma patients. Observational-cross-sectional study. A total of 334 eyes of 167 patients were included. All patients underwent confocal scanning laser ophthalmoscopy imaging in both eyes. Intereye concordance ratio of abnormal rim sectors as classified by the Moorfield regression analysis (MRA) was calculated as the ratio of matching abnormal rim areas to the total number of abnormal rim areas. The amount of agreement was calculated for each sector separately. Of the right (left) eyes, 39 (39) eyes were classified "borderline" (BL) by MRA, 62 (65) eyes were "within normal limits" (WNL), and 66 (63) eyes "outside normal limits" (ONL). A total of 78 patients had a normal overall MRA result in both eyes (BL = WNL). Of the 89 patients with a defect in at least one sector, mean intereye concordance was 0.28 +/- 0.04 (BL = WNL). When considering BL as ONL, concordance increased to 0.43 +/- 0.03. The lowest intereye agreement in rim abnormality was found in the temporal-inferior sector with 29.0% (Kappa +/- SE [standard error], 0.25 +/- 0.09, BL = WNL) matching. The highest agreement was found in the nasal- inferior sector with 47% (Kappa +/- SE, 0.53 +/- 0.1, BL = WNL) matching. There is a moderate intereye agreement in abnormal neuroretinal rim locations in eyes of ocular hypertensives, glaucoma suspects, and glaucoma patients. Longitudinal studies are needed to elucidate the agreement over time and to better understand the morphological pattern of progression between eyes in glaucoma.

Diagnostic Accuracy of the Moorfields Regression Analysis Using the Heidelberg Retina Tomograph in Glaucoma Patients with Visual Field Defects

This study was designed to determine the specificity and sensitivity of the Heidelberg Retina Tomograph I (HRT) using the Moorfields Regression Analysis (MRA) in differentiating healthy from glaucomatous eyes. In this cross-sectional study, 74 eyes of 37 healthy subjects and 87 eyes of 47 glaucoma patients were examined with Octopus standard automated perimetry and HRT. Only one eye per patient was used for statistical analysis. According to visual field index mean defect (MD) glaucoma patients were divided into three groups with early (MD < 6 dB), moderate (6 dB < MD < 12 dB), and advanced visual field loss (MD > 12 dB). The sensitivity and specificity of optic nerve head examinations using the MRA of HRT were evaluated by two criteria (criteria 1, as diseased if classified by MRA as outside normal limits; criteria 2, as diseased if classified by MRA as borderline). The correlations between the topographic parameters and visual field index MD were measured by correlation coefficient and presented by scatter plot. The specificity and sensitivity of HRT-MRA examination were, respectively, 100% and 68.1% when borderline cases were considered normal (criteria 1) and 97.3% and 85.1% when borderline cases were considered glaucomatous (criteria 2). The sensitivity of the MRA in eyes with different stages of visual field loss was 59.1% for early, 54.5% for moderate, and 92.8% for advanced visual field loss with criteria 1; the figures were, respectively, 81.8%, 72.7%, and 100% with criteria 2. The statistically significant correlations with moderate strength of association (r = 0.40-0.59) were found for rim area, rim volume, cup to disc area ratio, mean retinal nerve fiber layer (RNFL) thickness, and RNFL cross-sectional area. The MRA showed an excellent specificity and good sensitivity using criteria 2 including as glaucomatous optic discs those classified by MRA as borderline. Although correlations of moderate strength were found between rim area, rim volume, mean RNFL thickness, RNFL cross-sectional area, and visual field index MD, great interindividual variation limits the prediction of one parameter from the other. Therefore, in clinical practice both structural and functional examinations should be performed in order to characterize glaucomatous damage.

Comparing Multifocal VEP and Standard Automated Perimetry in High-Risk Ocular Hypertension and Early Glaucoma

To compare the diagnostic performance of multifocal visual evoked potential (mfVEP) and standard automated perimetry (SAP), in eyes with high-risk ocular hypertension or early glaucoma. Both eyes of 185 individuals with high-risk ocular hypertension or early glaucoma were evaluated. Subjects ranged in age from 37 to 87 (mean +/- SD: 61 +/- 11 years). Pattern-reversal mfVEPs were obtained by using VERIS (Electro-Diagnostic Imaging, San Mateo, CA) with a four-electrode array and were analyzed with custom software. SAP visual fields (SITA-standard; Carl Zeiss Meditec, Inc., Dublin, CA) were obtained within 22.3 +/- 27.0 days of the mfVEP. Stereo disc photographs and Heidelberg Retina Tomograph (HRT) images were obtained during one visit, which was within 24.8 +/- 50.4 days of the mfVEP and 33.1 +/- 62.9 days of the SAP visual field. Abnormalities on the mfVEP were defined by using a variety of cluster criteria: SAP with pattern standard deviation (PSD) P </= 0.05 or glaucoma hemifield test (GHT) outside normal limits, according to OHTS criteria (SAP-OHTS). In separate analyses cluster criteria were used to determine SAP abnormalities. Disc photographs were graded as either glaucomatous optic neuropathy (GON) or normal by two independent masked experts, and disagreements were adjudicated by a third masked expert. The overall Moorfields regression analysis (MRA) result from the HRT was used as a separate diagnostic classification. All eyes classified as "borderline" by the MRA were assigned to the normal category (i.e., "within normal limits"). Sensitivity for mfVEP or SAP was defined as the percentage of GON eyes that had an abnormality on the functional test. Specificity for mfVEP or SAP was defined as the percentage of eyes with normal optic disc structure that had normal functional test results. Disc photographs from 50% of eyes were graded GON. Both eyes were graded GON in 71 (38%) of the 185 subjects. Exactly half as many eyes were abnormal by HRT MRA. The average SAP mean deviation (MD) was +0.3 +/- 2.1 dB; average PSD was 2.3 +/- 1.9 dB. By OHTS criteria, 83 (22%) of the 370 eyes had an abnormal SAP. Depending on the cluster criterion used, the proportion of eyes with an abnormal SAP ranged from 8% to 26% and with an abnormal mfVEP, from 14% to 45%. A criterion with an estimated specificity in normal subjects of 91% resulted in 102 (28%) eyes with an abnormal mfVEP. For criteria with estimated specificities of 95% and 99%, respectively, 88 (24%) eyes and 52 (14%) eyes had an abnormal mfVEP. Agreement between SAP and mfVEP ranged from 75% to 81%. The sensitivity of SAP-OHTS to detect GON (using the disc photograph as diagnostic standard) was 29%, whereas specificity was 84%. Sensitivity of the mfVEP to detect GON, for cluster criteria with disc structure specificity between 84% and 87%, ranged from 28% to 32%. When the HRT MRA was used as the diagnostic standard, sensitivities of both functional tests to detect GON increased to 42%. The diagnostic performance of mfVEP was similar to that of SAP. However, the two modalities agreed in only approximately 80% of eyes, suggesting that they may detect slightly different functional deficits.

Diagnostic Ability of the Heidelberg Retina Tomograph, Optical Coherence Tomograph, and Scanning Laser Polarimeter in Open-angle Glaucoma

To compare the ability to discriminate between healthy and glaucomatous eyes of different criteria based on parameters from 3 optical imaging devices: Heidelberg retina tomograph (HRT-II), optical coherence tomograph (Stratus OCT 3000) and scanning laser polarimeter (GDx VCC). Cross-sectional study. A total of 139 eyes from 139 subjects were enrolled in this study and classified into 66 healthy subjects and 73 glaucomatous patients according to intraocular pressure and standard automated perimetry. All the subjects underwent complete ophthalmic examination, including HRT-II, OCT, and GDx VCC evaluations. Several parameters were obtained by these techniques and 8 diagnostic criteria were assessed. Receiver operating characteristics curves were plotted and compared among them, and sensitivity for specificity higher than 95% was calculated for every criterion. Agreement among the 3 technologies was assessed by means of Venn diagrams. The best criteria discriminating between healthy and glaucomatous eyes were Moorfields regression analysis out of the 95% confidence interval (HRT-II), OCT retinal nerve fiber layer average thickness <77 microm, and nerve fiber indicator >37 (GDx VCC) with sensitivities of 85%, 66%, and 48%, with specificity higher than 95%. Sixty-six patients out of 73 were correctly identified by at least 1 of the devices and 30 were detected by the 3 of them. Structural criteria assessed by the optical imaging devices evaluated in this study are useful to discriminate glaucomatous damage.

Automated Analysis of Heidelberg Retina Tomograph Optic Disc Images by Glaucoma Probability Score

To compare the diagnostic performance of the Heidelberg Retinal Tomograph's (HRT; Heidelberg Engineering GmbH, Dossenheim, Germany) glaucoma probability score (GPS), an automated, contour line-independent method of optic disc analysis with that of the Moorfields regression analysis (MRA). HRT images were obtained from one eye of 121 patients with glaucoma (median age, 70.2 years; median mean deviation [MD], -3.6 dB, range, +2.0 to -9.9 dB) and 95 healthy control subjects (median age, 59.7 years; median MD -0.1 dB, range +2.5 to -3.7). The diagnostic performances of GPS and MRA were evaluated by including borderline classifications, either as test negatives (most specific criteria) or as test positives (least specific criteria). Agreement between global and sectoral data of both analyses was established. Logistic regression analyses were performed to evaluate the effect of covariates such as optic disc size and age on the classification outcomes of both the GPS and the MRA. In 8 (7%) patients with glaucoma and 10 (11%) control subjects, the GPS failed to provide a complete global and sectoral optic disc classification. Although we could not identify a single distinct cause of this failure in the glaucoma group, failures in the control subjects occurred most often (7/10) with small and crowded optic discs. In subjects who were successfully classified at least globally by the GPS (117 patients with glaucoma, 88 control subjects), the diagnostic performances of GPS and MRA were similar (areas under the receiver operating characteristic [ROC] curve of 0.78 and 0.77, respectively; P > 0.1). With the GPS, sensitivity and specificity were 59% and 91% (most specific criteria) and 78% and 63% (least specific criteria), respectively. Combining GPS and MRA did not increase diagnostic performance significantly (ROC area of combined classifiers, 0.81). Both GPS and MRA were affected by disc size. In patients with glaucoma as well as healthy control subjects, the odds of a positive GPS classification (borderline or outside normal limits) increased by 21% (95% confidence interval [CI], 12%-30%) for each 0.1 mm2 increase in optic disc area. With the MRA, the corresponding increase was 15% (95% CI, 7%-23%). Optic disc area alone accounted for approximately 30% and 22% of the explained variance with the GPS and MRA, respectively (P < 0.001). The proportional-odds logistic regression confirmed that optic disc size affected mainly the tradeoff between true- and false-positive classifications (criterion) rather than the absolute performance of the analyses (area under the ROC curve). There was some evidence of an age effect with the MRA, which showed a 53% (95% CI, 16%-102%) increase in the odds of a positive test (borderline or outside normal limits) associated with each decade of age (P = 0.002), but no age effects were observed with the GPS (P > 0.1). The diagnostic performance of the contour line-independent GPS analysis is similar to that of the MRA. However, clinicians should be aware of the strong size dependence of both GPS and MRA. In large optic discs, both GPS and MRA are likely to produce many false-positive classifications. Correspondingly, the sensitivity to early damage is likely to be low in small optic discs. There is a need for automated classification systems that explicitly address the size dependence of current analyses.

Assessment of a Race-specific Normative HRT-III Database to Differentiate Glaucomatous From Normal Eyes

To determine if a new, normative, race-specific database enhances the ability of confocal scanning laser ophthalmoscopy to differentiate normal from glaucomatous eyes. One eye of eligible normal and glaucoma patients was enrolled. All subjects underwent a complete ophthalmologic examination, standard achromatic perimetry (SITA-SAP, 24-2), and confocal scanning laser ophthalmoscopy [Heidelberg retinal tomograph (HRT-II)] within 1 month of enrollment. Racial groups were defined by self-report. Glaucoma was defined by the existence of reproducible SAP loss (pattern standard deviation <5% and/or Glaucoma Hemifield Test outside normal limits) on 2 consecutive fields. Normal subjects had 2 normal visual fields (pattern standard deviation >5% and Glaucoma Hemifield Test within 97% normal limits) and a normal clinical examination. HRT-II examinations were exported to the HRT-III software, which includes a large race-specific normative database consisting of 733 white and 215 black eyes. Moorfields regression analysis (MRA) for the most abnormal optic disc sector was compared between the HRT-II (MRA2) and the HRT-III software before (MRA3-B) and after (MRA3-A) adjustment for race. Sectors outside the 99.9% confidence interval limits ("outside normal limits") were determined to be abnormal. We enrolled 124 black (52 glaucoma, 72 normal) and 96 white (32 glaucoma, 64 normal) subjects. Mean age was 51+/-13 years and 50+/-16 years for blacks and whites, respectively (P = 0.45). Visual field mean deviation was -7.3+/-6.7 db for glaucomatous eyes and -0.4+/-1.1 db for normal eyes (P < 0.001). Sensitivity and specificity for the HRT-II was 71.9% and 95.3%, respectively, for white subjects and 50.0% and 98.6%, respectively, for black subjects. Using the expanded HRT-III database, analysis yielded a sensitivity of 81.3% and specificity of 93.8% for whites and a sensitivity of 71.2% and specificity of 86.1% for blacks. After an adjustment for black ethnicity was made in the HRT-III program, the sensitivity and specificity for blacks was 65.4% and 90.3%, respectively. A new, larger, race-specific HRT-III database increases sensitivity while maintaining specificity for whites and increases sensitivity but decreases specificity for blacks. New software and databases based on race require careful scrutiny before use in clinical practice.

Glaucoma Detection with the Heidelberg Retina Tomograph 3

To compare the ability of the Heidelberg retina tomograph version 3 (HRT 3) and HRT version 2 (HRT 2) to discriminate between healthy and glaucomatous eyes. Retrospective cross-sectional study. Seventy-one eyes of 71 healthy volunteers and 50 eyes of 50 glaucoma patients were studied. The average visual field mean deviation of the glaucoma group was -6.03+/-5.78 dB. All participants had comprehensive ocular examinations, perimetry, and HRT scanning within 6 months. HRT 2 data were analyzed using HRT 3 software without modifying the disc margin. Discrimination capabilities between healthy and glaucomatous eyes were determined by areas under the receiver operating characteristics (AROCs) curves. Comparisons between corresponding AROCs obtained by HRT 2 and HRT 3 analyses were performed using the nonparametric DeLong method. Agreement between classifications as defined by the different analysis methods was quantified by kappa analysis. The individual stereometric parameters with the best discrimination were linear cup/disc ratio (AROC = 0.897; 95% confidence interval [CI], 0.836-0.958) for standard HRT 3 analysis and horizontal retinal nerve fiber layer curvature (0.905) for HRT 3 glaucoma probability score (GPS) analysis. Areas under the receiver operating characteristics for discrimination between glaucomatous and healthy eyes of the overall classification by HRT 2 Moorfields regression analysis (MRA), HRT 3 MRA, and GPS were 0.927 (95% CI, 0.877-0.977), 0.934 (0.888-0.980), and 0.880 (0.812-0.948), respectively. The difference between the 3 AROCs was not significant (P = 0.44). The agreement between HRT 2 and HRT 3 overall MRA classification was good (kappa = 0.70; CI, 0.59-0.80) with HRT 3 tending to report more abnormalities than HRT 2 analysis. The agreement between overall HRT 3 MRA and overall GPS was kappa = 0.58 (CI, 0.45-0.70). The glaucoma discriminating ability of the new HRT 3 software is similar to that of the previous generation HRT 2. The GPS analysis showed promising results in differentiating between healthy and glaucomatous eyes without the need for subjective operator input.

Topography and Fluorescein Angiography of the Optic Nerve Head in Primary Open-Angle and Chronic Primary Angle Closure Glaucoma

The purpose of this study is to correlate optic nerve head topography with fluorescein angiography of the optic nerve head in patients with primary open-angle glaucoma (POAG), chronic primary angle closure glaucoma (CPACG), and normal controls. This was an institution-based, cross-sectional, case-control study of 30 consecutive patients each with POAG or CPACG, which were compared with 30 age- and sex-matched controls. The fluorescein angiograms undertaken in one eye of each of the 90 subjects were then analyzed both qualitatively and quantitatively. The mean age of controls (group 1) was 51.73 +/- 9.6 years, patients with CPACG (group II) was 53.26 +/- 9.5 years, and patients with POAG (group III) was 54.5 +/- 10.4 years. The mean deviation and corrected pattern standard deviation on Humphrey visual field analyzer, respectively, were -1.51 +/- 2.01 dB and 2.09 +/- 1.04 dB the in control group, -9.4 +/- 9.3 dB and 5.32 +/- 4.02 dB in the CPACG group, and -11.27 +/- 7.7 dB and 7.57 +/- 5.34 dB in the POAG group. There was no significant difference in the disc areas between the three groups (analysis of variance [ANOVA], p = 0.157). All circulatory parameters were delayed in both glaucoma groups compared with controls with the disc filling time (ANOVA, p = 0.001) and the choroidal filling time being significantly delayed (ANOVA, p = 0.006). The Moorfield regression analysis showed good correlation with the pattern of disc fluorescence in all quadrants in cases of CPACG and POAG. The optic nerve head and choroidal circulation was delayed in both patients with POAG and those with CPACG, which correlates with loss of neuroretinal rim and retinal nerve fiber layer on the Heidelberg Retina Tomograph II (HRT). Patients with POAG showed diffuse damage with significant rim loss, whereas patients with CPACG showed marked sectorial abnormalities (superotemporal and the inferior-temporal) on fluorescein angiography and HRT. One possible reason for this discrepancy could be sectorial ischemia occurring in cases of CPACG as a result of a sudden rise of intraocular pressure causing disc and visual field damage.

Specificity of the Heidelberg Retina Tomograph’s Diagnostic Algorithms in a Normal Elderly Population: The Bridlington Eye Assessment Project

To determine the specificity of the Moorfields regression analysis (MRA) and R. Burk (RB) and F. S. Mikelberg (FSM) linear discriminant functions (LDFs) in classifying the optic discs of normal elderly patients imaged with the Heidelberg Retina Tomograph. Cross-sectional study. Optic nerve head analysis of 459 eyes of 459 normal elderly patients was performed by 2 operators. All patients were consecutive in a cohort screened for eye disease. Normals were defined as having a normal visual field (VF) on automated suprathreshold screening, normal intraocular pressure, and normal visual acuity. Specificity of the optic nerve head classification by MRA and the RB and FSM LDFs. Subjects' mean age (262 female, 197 male) was 72.6 years. Males were found to have significantly larger cups than females. Eighty-three percent, 11.3%, and 5.7% of discs were classed as within normal limits, borderline, and outside normal limits by MRA. Percentages of optic discs classified as outside normal limits in the smallest and largest quartiles for disc size were 0.9% and 14.9%. The association of disc size with the classification of outside normal limits was significant in males only. Agreement in MRA classification between 2 investigators separately placing the optic disc contour was moderate (Cohen's kappa = 0.54, P<0.001). The RB and FSM LDFs classified 6.8% and 11.8% of discs as diseased. The RB LDF was significantly more likely to return a diagnosis of disease in larger discs, though only in males. The FSM LDF tended to the same drop in specificity, although not significantly. Using the MRA and RB/FSM LDFs, specificity fell dramatically with increasing disc size, particularly in males. This may reflect the finding of significantly larger cups in males than in females in the normal elderly population. This divergence was not predicted by these diagnostic functions, which were developed on samples of younger subjects.

Comparison of Objective Diagnostic Tests in Glaucoma

To compare sensitivity and specificity of functional and structural changes in glaucoma using two objective tests: the multifocal visual evoked potential (m-VEP) and Heidelberg retinal tomography II (HRT). 41 glaucoma patients and 25 normal individuals participated in the study. One eye per individual was included in the study. Individuals were evaluated with Humphrey visual field (HVF) perimetry, m-VEP, and HRT. Moorfield regression analysis findings of HRT were compared with presence of scotoma on m-VEP. Linear regression analysis of quantitative variables, such as HVF mean deviation (MD), m-VEP discriminant score (Accumap Severity Index) and, global HRT parameters was also performed. m-VEP sensitivity and specificity were 93% and 96% respectively. HRT sensitivity and specificity were 79% and 92% respectively. The area under the receiver operating characteristic curve (ROC) for m-VEP was 0.96 and for HRT varied from 0.79 to 0.86 depending on the parameters used. Linear correlation between MD and Accumap Severity Index score was -77%, while that between HRT global parameters, Accumap Severity Index and MD were at best around 50%. Topographic comparison of the presence of scotoma on HVF and m-VEP in different areas of the visual field showed good agreement. Comparison of optic nerve head structural abnormality with corresponding areas of field defects on HVF and m-VEP showed poor to moderate agreement. The objective test of optic nerve function (m-VEP) and structure (HRT) can detect glaucomatous damage, with limited correlation. The 2 functional tests, HVF and m-VEP correlate better with each other than with HRT. It remains important to look for both functional and structural changes in order to detect all glaucoma cases.

Análisis de la distribución de anillo neurorretiniano por sectores mediante láser confocal de barrido en el diagnóstico del glaucoma

To evaluate the diagnostic ability of the Moorfields regression analysis (MRA; neuroretinal rim sector-based analysis) by means of confocal scanning laser. 200 eyes were included in this study: 101 normal subjects and 99 glaucoma patients (standard automated perimetry with glaucomatous defects -MD or CPSD with p<0.02 or a cluster of three or more points with p<0.05 or a cluster of two or more points with p<0.01 or abnormal Glaucoma Hemifield Test). All subjects underwent a full ophthalmic evaluation, visual field evaluation by means of a Humphrey Field Analyzer, 24-2 full threshold strategy, and optic disc topography by Heidelberg retina tomograph (HRT-II). The outcome parameters were sensitivity and specificity of the MRA for each sector. The highest sensitivity in detecting structural defects based on MRA (p<0.05) was observed in the nasal-superior sector (48%) and nasal-inferior sector (45%); however the highest specificity was found in the temporal-superior (98%) and inferior (98%) sectors. The highest sensitivity for MRA (p<0.01) was found in the temporal-inferior sector (31%) and nasal-superior sector (30%) while the temporal-superior and inferior-sectors showed the highest specificity (100%). The diagnosis of glaucoma based on the presence of any sector alteration showed sensitivity figures of 67% with p<0.05 and 46% with p<0.01 and specificity values of 84% with p<0.05 and 96% with p<0.01. The analysis of the distribution of the neuroretinal rim by means of HRT-II contributes effectively to the diagnosis of glaucoma based on perimetry in a sample derived from a Spanish population.

Influence of Disease Severity and Optic Disc Size on the Diagnostic Performance of Imaging Instruments in Glaucoma

To evaluate the influence of disease severity and optic disc size on the diagnostic accuracy of three imaging technologies for structural assessment in glaucoma: confocal scanning laser ophthalmoscopy, scanning laser polarimetry, and optical coherence tomography. One hundred five patients with glaucoma and 61 normal subjects were recruited from the Diagnostic Innovations in Glaucoma Study (DIGS). All individuals underwent imaging with the GDx Variable Corneal and Lens Compensator (VCC; Carl Zeiss Meditec, Inc., Dublin, CA), the Heidelberg Retina Tomograph II (HRT II; Heidelberg Engineering, GmbH, Dossenheim, Germany), and the Stratus OCT (Stratus OCT; Carl-Zeiss Meditec, Inc.) within a 6-month period. Severity of disease was based on the AGIS (Advanced Glaucoma Intervention Study) visual field score. To evaluate the influence of severity of glaucoma and optic disc size on the diagnostic accuracy of the imaging instruments, the sensitivities of the tests were fitted as a function of the AGIS score and disc area, by using logistic marginal regression models. The severity of visual field loss had a significant influence on the sensitivity of all imaging instruments. More severe disease was associated with increased sensitivity. This influence was similar among the three instruments. With regard to optic disc area, larger optic discs were associated with decreased sensitivity for the Stratus OCT parameter Average Thickness and the GDx VCC parameter Nerve Fiber Indicator, whereas small optic discs were associated with increased sensitivity. For the HRT II parameter Moorfields regression analysis classification, an inverse effect was observed. The diagnostic performances of the GDx VCC, HRT II, and Stratus OCT were significantly influenced by the severity of the disease and optic disc size. These covariates should be taken into account when comparing the performances of these tests for glaucoma diagnosis.

Heidelberg Retinal Tomograph (HRT 2) Parameters in Primary Open Angle Glaucoma and Primary Angle Closure Glaucoma: A Comparative Study in an Indian Population

Aims: To compare the Heidelberg Retinal Tomograph (HRT 2) parameters in patients with primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG) in an Indian population. Materials and Methods: Two groups of patients were recruited: group I comprised 78 eyes (78 patients) with POAG and group II 58 eyes (58 patients) with PACG. Based on visual field defects detected by automated perimetry, the groups were further classified into early, moderate, and severe glaucoma. All patients underwent a complete ophthalmic examination as well as an HRT 2 examination. The HRT parameters for the two groups were compared and the sensitivity and specificity of the parameters calculated. Results: All HRT parameters were similar in both groups: 85.9% (95% CI: 78.2, 93.6) of POAG and 81% (95% CI: 72.3, 89.3) of PACG had a positive F. S. Mikeleberg (FSM) discriminant function. Considering outside normal limits and borderline as abnormal, the Moorefield regression analysis had 83.3% (95% CI: 75, 91.6) sensitivity in POAG and 75.9% (95% CI: 64.9, 86.9) in PACG. In early POAG, the FSM discriminant function had a sensitivity of 74.3% (95% CI: 59.8, 88.8) compared to 58.3% (95% CI: 38.9, 77.7) for early PACG. The cup shape measure (p = 0.018) and the Moorfield regression analysis (p = 0.011) had significantly higher sensitivity for early POAG than for early PACG: cup shape measure sensitivity 62.9% (95% CI 46.9, 78.9) for early POAG versus 33.3% (95% CI: 14.4, 52.2) for early PACG and Moorefield regression analysis 74.3% (95% CI: 59.8, 88.8) versus 45.8% (95% CI: 39.9, 65.7). Conclusions: HRT has moderate sensitivity in the detection of damage leading to glaucomatous field defects. The sensitivity of HRT for early PACG appears to be less than that for early POAG. This may indicate a difference in pathophysiology.

Validity of Screening for Glaucomatous Optic Nerve Damage Using Confocal Scanning Laser Ophthalmoscopy (Heidelberg Retina Tomograph II) in High-Risk Populations: A Pilot Study

To evaluate whether confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph II [HRT II], Heidelberg Engineering, Heidelberg, Germany) is a valid tool for the detection of glaucomatous optic nerve damage. Observational, cross-sectional, nonconsecutive study in Montreal, Canada. Three hundred three nonconsecutive, high-risk persons were enrolled during a 6-month period. Participants underwent HRT II testing and a standard ophthalmologic examination, including gonioscopy, intraocular pressure measurement, and optic disc grading. Positive likelihood ratio (PLR) and negative likelihood ratio (NLR), sensitivities and specificities, positive predictive value (PPV) and negative predictive value (NPV), and kappa coefficients of agreement of Moorfields regression analysis (MRA), cup shape measure (CSM), height variation contour (HVC), and mean retinal nerve fiber layer thickness (MRNFL). Three hundred three participants were enrolled, and 291 were examined clinically; 21 (7.2%) were found to have glaucoma. Heidelberg Retina Tomograph II testing was performed successfully and was of acceptable quality in 531 of 601 eyes (88%). When MRA was compared with the clinically based diagnosis, the weighted kappa coefficient was kappa = 0.567 (95% confidence interval [CI], 0.42-0.71) for the right eye and kappa = 0.516 (95% CI, 0.37-0.66) for the left eye. Best kappa coefficient of agreement was seen when normals were grouped with suspects in both clinical and MRA diagnosis (kappa = 0.604; 95% CI, 0.409-0.799 in the right eye). Depending on the gold standard and test-positive definitions for glaucoma, specificity ranged from 87% to 97%, sensitivity from 25% to 100%, PPV from 28% to 68%, NPV from 84% to 100%, PLR from 5.0 to 19.2, and NLR from 1.3 to 6.2. When CSM, HVC, and MRNFLT were compared with clinical diagnosis, all outcome measures were found to have lower ranges: specificity from 46.9% to 83.7%, sensitivity from 36.5% to 76.9%, PPV from 6% to 36%, NPV from 80% to 99%, PLR from 0.8 to 4.0, NLR from 0.9 to 3.0. The results of this study suggest that a glaucoma screening program may be effective in detecting glaucoma when targeting high-risk populations. Heidelberg Retina Tomograph II testing may prove to be a useful tool in detecting glaucomatous optic nerve damage and could be used as part of a complete glaucoma screening protocol.

Baseline Topographic Optic Disc Measurements Are Associated With the Development of Primary Open-Angle Glaucoma

To determine whether baseline confocal scanning laser ophthalmoscopy (CSLO) optic disc topographic measurements are associated with the development of primary open-angle glaucoma (POAG) in individuals with ocular hypertension. Eight hundred sixty-five eyes from 438 participants in the CSLO Ancillary Study to the Ocular Hypertension Treatment Study with good-quality baseline CSLO images were included in this study. Each baseline CSLO parameter was assessed in univariate and multivariate proportional hazards models to determine its association with the development of POAG. Forty-one eyes from 36 CSLO Ancillary Study participants developed POAG. Several baseline topographic optic disc measurements were significantly associated with the development of POAG in both univariate and multivariate analyses, including larger cup-disc area ratio, mean cup depth, mean height contour, cup volume, reference plane height, and smaller rim area, rim area to disc area, and rim volume. In addition, classification as "outside normal limits" by the Heidelberg Retina Tomograph classification and the Moorfields Regression Analysis classifications (overall, global, temporal inferior, nasal inferior, and superior temporal regions) was significantly associated with the development of POAG. Within the follow-up period of this analysis, the positive predictive value of CSLO indexes ranged from 14% (Heidelberg Retina Tomograph classification and Moorfields Regression Analysis overall classification) to 40% for Moorfields Regression Analysis temporal superior classification. Several baseline topographic optic disc measurements alone or when combined with baseline clinical and demographic factors were significantly associated with the development of POAG among Ocular Hypertension Treatment Study participants. Longer follow-up is required to evaluate the true predictive accuracy of CSLO measures.