Article

Predicting Progression to Glaucoma in Ocular Hypertensive Patients

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Abstract

To assess the ability of Heidelberg Retina Tomograph (HRT) Moorfields Regression Analysis (MRA) and Glaucoma Probability Score (GPS) classifications at baseline to predict glaucomatous progression in ocular hypertensive eyes. One hundred ninety-eight ocular hypertensive subjects underwent regular HRT and visual field (VF) testing from 1993 to 2001. HRT progression was assessed using linear regression of rim area/time. VF progression was assessed by pointwise linear regression of sensitivity/time. Subjects were classified as progressing or stable at the end of the study period. The relationship between baseline abnormal (outside normal limits combined with borderline classification) MRA and GPS classification and progression status was assessed by odds ratios (ORs). An abnormal superotemporal MRA was the only classification found to be predictive of HRT progression in isolation (OR 3.05, 1.25-7.47). Abnormal global, superotemporal, superonasal, and temporal MRA classifications were all associated with significant ORs for predicting HRT or VF progression (OR range: 1.77-2.54). Abnormal GPS classifications were not predictive of disease behavior. Combined abnormal GPS and MRA classifications were associated with higher ORs than either classification in isolation. Patients with an abnormal MRA and GPS classification at presentation may be at increased risk of HRT or VF change.

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... Similar findings have been reported using CSLO and OCT. Strouthidis and colleagues found neither baseline MRA nor GPA classification alone were good at predicting future progression of visual field in patients with OHT (Strouthidis et al 2010), though abnormal CSLO at baseline was associated with increased risk of further structural changes. Although it is possible that baseline structural measures might have been better at predicting an alternative functional endpoint, they were also poorly predictive of future visual field loss in the CSLO ancillary study to the OHTS . ...
Conference Paper
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BACKGROUND: Imaging is widely used to quantify glaucomatous structural changes. Although previous studies have examined the relationship between structure and function, measured using standard automated perimetry (SAP), the true relevance of structural changes remains poorly understood. AIM: The aim of this body of work was to explore the structure-function relationship and to ascertain the point at which structural changes become associated with impaired ability to perform vision-dependent tasks. PLAN OF RESEARCH: After critically appraising previously described structurefunction models, an investigation was conducted progressively evaluating the relationship between glaucomatous structural changes and 1) estimated loss of retinal ganglion cells (RGCs), 2) an objective measure of visual function (the pupil response), and 3) a vision-related task relevant to quality of life (driving). RESULTS: Localised RNFL defects visible on photographs, a common manifestation of glaucoma, were associated with large estimated RGC losses. However, problems were identified with the published method of RGC estimation. Asymmetric RNFL thinning was also found to be associated with asymmetry of the pupil response, and the magnitude of asymmetry required for a clinically detectable relative afferent pupillary defect (RAPD) was calculated. Finally, loss of RNFL was associated with worse ability to perform a simulated driving task, providing additional information to SAP alone. SIGNIFICANCE: Glaucomatous structural defects may be associated with significant functional impairment. Incorporating information from both structure and function may improve our ability to predict patients at risk of developing problems with vision-related tasks of daily living.
... Several prior studies have looked at ocular hypertensives or glaucoma suspects and the role of imaging at baseline to predict conversion to glaucoma. Abnormal baseline measurements using confocal scanning laser ophthalmoloscope (cSLO) scans, 33 scanning laser polarimetry, 34 and NFL thickness with OCT 35 have all been shown to predict glaucomatous VF change in ocular hypertensive glaucoma suspects. In a report analysing early data from the AIG Study with TDOCT, scanning laser polarimetry, and cSLO, abnormal baseline ONH topography and thin inferior retinal NFL were reported to be predictive of VF progression in a smaller sample of glaucoma suspects and patients. ...
Article
Purpose: To identify baseline structural parameters that predict the progression of visual field (VF) loss in patients with open-angle glaucoma. Design: Multicenter cohort study. Methods: Participants from the Advanced Imaging for Glaucoma (AIG) study were enrolled and followed up. VF progression is defined as either a confirmed progression event on Humphrey Progression Analysis or a significant (P < .05) negative slope for VF index (VFI). Fourier-domain optical coherence tomography (FDOCT) was used to measure optic disc, peripapillary retinal nerve fiber layer (NFL), and macular ganglion cell complex (GCC) thickness parameters. Results: A total of 277 eyes of 188 participants were followed up for 3.7 ± 2.1 years. VF progression was observed in 83 eyes (30%). Several baseline NFL and GCC parameters, but not disc parameters, were found to be significant predictors of progression on univariate Cox regression analysis. The most accurate single predictors were the GCC focal loss volume (FLV), followed closely by NFL-FLV. An abnormal GCC-FLV at baseline increased risk of progression by a hazard ratio of 3.1. Multivariate Cox analysis showed that combining age and central corneal thickness with GCC-FLV in a composite index called "Glaucoma Composite Progression Index" (GCPI) further improved the accuracy of progression prediction. GCC-FLV and GCPI were both found to be significantly correlated with the annual rate of change in VFI. Conclusion: Focal GCC and NFL loss as measured by FDOCT are the strongest predictors for VF progression among the measurements considered. Older age and thinner central corneal thickness can enhance the predictive power using the composite risk model.
... Studies have demonstrated that abnormal baseline ONH topography and thin retinal nerve fiber layer thickness (RNFLT) measurements are predictive of future visual-field loss. [5][6][7][8][9][10][11][12][13] Although structural risk factors associated with glaucoma progression have been studied in glaucoma suspect (GS) eyes, to our knowledge no studies have prospectively compared the predictive power of various posterior segment imaging technologies in a cohort of glaucomatous eyes. ...
Article
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PurposeThe objective of this study is to assess whether baseline optic nerve head (ONH) topography and retinal nerve fiber layer thickness (RNFLT) are predictive of glaucomatous visual-field progression in glaucoma suspect (GS) and glaucomatous eyes, and to calculate the level of risk associated with each of these parameters.Methods Participants with ≥28 months of follow-up were recruited from the longitudinal Advanced Imaging for Glaucoma Study. All eyes underwent standard automated perimetry (SAP), confocal scanning laser ophthalmoscopy (CSLO), time-domain optical coherence tomography (TDOCT), and scanning laser polarimetry using enhanced corneal compensation (SLPECC) every 6 months. Visual-field progression was assessed using pointwise linear-regression analysis of SAP sensitivity values (progressor) and defined as significant sensitivity loss of >1 dB/year at ≥2 adjacent test locations in the same hemifield at P<0.01. Cox proportional hazard ratios (HR) were calculated to determine the predictive ability of baseline ONH and RNFL parameters for SAP progression using univariate and multivariate models.ResultsSeventy-three eyes of 73 patients (43 GS and 30 glaucoma, mean age 63.2±9.5 years) were enrolled (mean follow-up 51.5±11.3 months). Four of 43 GS (9.3%) and 6 of 30 (20%) glaucomatous eyes demonstrated progression. Mean time to progression was 50.8±11.4 months. Using multivariate models, abnormal CSLO temporal-inferior Moorfields classification (HR=3.76, 95% confidence interval (CI): 1.02-6.80, P=0.04), SLPECC inferior RNFLT (per -1 μm, HR=1.38, 95% CI: 1.02-2.2, P=0.02), and TDOCT inferior RNFLT (per -1 μm, HR=1.11, 95% CI: 1.04-1.2, P=0.001) had significant HRs for SAP progression.Conclusion Abnormal baseline ONH topography and reduced inferior RNFL are predictive of SAP progression in GS and glaucomatous eyes.Eye advance online publication, 12 October 2012; doi:10.1038/eye.2012.203.
... 5,39,40 Different attempt have been made to generate models that predict visual function from RNFL structure. 6,8,41 The purpose of this study was not to evaluate the agreement between structural and functional progression methods, but our aim was to prospectively compare RNFL progression with visual field progression using trend-based analysis, and explore whether RNFL loss is predictive of subsequent visual field loss. Quite often the structural and functional progression do not happen simultaneously within a certain period of time, but if the patient is followed up long enough, eventually both structural and functional progression will confirm the findings of the other method. ...
Article
Purpose: To compare prospectively detection of progressive retinal nerve fiber layer thickness (RNFL) atrophy identified using time-domain optical coherence tomography with visual field progression using standard automated perimetry in glaucoma suspect and preperimetric glaucoma patients or perimetric glaucoma patients. Design: Prospective, longitudinal clinical trial. Methods: Eligible eyes with 2 years or more of follow-up underwent time-domain optical coherence tomography and standard automated perimetry every 6 months. The occurrence of visual field progression was defined as the first follow-up visit reaching a significant (P < .05) negative visual field index slope over time. RNFL progression or improvement was defined as a significant negative or positive slope over time, respectively. Specificity was defined as the number of eyes with neither progression nor improvement, divided by the number of eyes without progression. Cox proportional hazard ratios were calculated using univariate and multivariate models with RNFL loss as a time-dependent covariate. Results: Three hundred ten glaucoma suspect and preperimetric glaucoma eyes and 177 perimetric glaucoma eyes were included. Eighty-nine eyes showed visual field progression and 101 eyes showed RNFL progression. The average time to detect visual field progression in those 89 eyes was 35 ± 13 months, and the average time to detect RNFL progression in those 101 eyes was 36 ± 13 months. In multivariate Cox models, average and superior RNFL losses were associated with subsequent visual field index loss in the entire cohort (every 10-μm loss; hazard ratio, 1.38; P = .03; hazard ratio, 1.20; P = .01; respectively). Among the entire cohort of 487 eyes, 42 had significant visual field index improvement and 55 had significant RNFL improvement (specificity, 91.4% and 88.7%, respectively). Conclusions: Structural progression is associated with functional progression in glaucoma suspect and glaucomatous eyes. Average and superior RNFL thickness may predict subsequent standard automated perimetry loss.
... Research outcomes regarding the predictability of structural change assessed by imaging devices for future VF development is relatively scarce. 4,[23][24][25] For various reasons, long-term follow-up studies tend to be more difficult to perform than cross-sectional studies. Constant updating of versions of imaging devices may make it difficult to examine patients with the same equipment longitudinally. ...
Article
To evaluate the utility of baseline Stratus optical coherence tomography (OCT; Carl Zeiss Meditec, Dublin, CA) retinal nerve fiber layer (RNFL) normative classification in the prediction of future visual field (VF) loss. Eighty-eight eyes with suspected glaucoma with abnormal RNFL classification by Stratus OCT were followed up for more than 4 years. VF conversion in three consecutive tests was assessed after baseline Stratus OCT and VF examination. Baseline intraocular pressure, VF global indices, OCT RNFL thickness, and number of abnormal OCT sectors were compared between VF converters (CG) and nonconverters (NCG). Positive and negative predictive values (PPV, NPV) of OCT sectors with abnormal classifications were calculated with respect to VF conversion. Hazard ratios (HRs) of various risk factors, including abnormal OCT classification, with respect to future VF conversion, were determined by use of the Cox proportional hazard model. Twenty-one (23.9%) eyes showed VF conversion during follow-up. Baseline OCT RNFL thickness was significantly lower and the number of abnormal OCT RNFL sectors significantly greater in CG than in NCG patients (P = 0.022 for both). The PPV and NPV of normative OCT RNFL classification was highest in the inferior quadrant (50%, 87.1%, respectively). Baseline VF mean deviation (MD) and the number of abnormal OCT RNFL sectors were both associated with future VF conversion (HR, 0.788 and 1.290, respectively). In patients with suspected glaucoma, an abnormal RNFL classification in the inferior area of the optic disc or an elevated number of abnormal RNFL sectors, as determined by Stratus OCT, were both associated with future VF conversion.
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Heidelberg Retina Tomograph (HRT) is a confocal scanning laser ophthalmoscope which acquires and analyzes 3-dimensional images of the optic nerve head. The latest instrument HRT3 includes software with larger ethinic-specific normative database. This review summarizes relevant published literature on HRT in diagnosing glaucoma, detecting glaucoma progression, the diagnostic accuracy of HRT among other imaging devices and its role in clinical practice.
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Aim: To compare and correlate optic nerve head parameters obtained by Heidelberg retina tomograph (HRT) with short-wavelength automatic perimetry (SWAP) indices in eyes with ocular hypertension (OHT). Methods: One hundred and forty-six patients with OHT included in the present study. All subjects had reliable SWAP and HRT measurements performed within a 2wk period. The eyes were classified as normal/abnormal according to visual field criteria and Moorfields regression analysis (MRA). Correlations between visual field indices and HRT parameters were analyzed using Pearson correlation coefficient (r). Results: Twenty-nine eyes (19.9%) had SWAP defects. Twenty-nine eyes (19.9%) were classified as abnormal according to global MRA. Six eyes (4.1%) had abnormal global MRA and SWAP defects. The k statistic is 0.116 (P=0.12) indicating a very poor agreement between the methods. No statistical significant correlation between HRT and SWAP parameters was detected. Conclusion: SWAP defects may coexist with abnormalities of optic disc detected by HRT in eyes with OHT. In most eyes, however, the two methods detect different glaucoma properties.
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Background: The incidence and progression of glaucomatous optic neuropathy is related to a disturbance of the retrobulbar hemodynamics. Compound anisodine is clinically applied for the treatment of ischemic ocular diseases. Objective: To evaluate the effects of compound anisodine injection on the ocular blood flow of glaucoma patients. Methods: Twenty-one patients with primary glaucoma were divided into the treatment group and the control group. The eyes of each patient in the treatment group were selected further into the treatment eye group (11 eyes with greater mean deviation [MD]) or the opposite eye group(11 eyes with lesser MD). One of the eyes of each patient in the control group with MD value were selected as control eyes (10 eyes). The treatment eye group received compound anisodine on the para-superficial temporal artery via subcutaneous injection once a day for 2 treatment periods (each period equals 14 days, with 7 days intermittent between periods, totally 35 days) in addition to routine treatment. The retrobulbar blood flow, optic disc data, refraction error, visual field and intraocular pressure were measured in 3 time points; Before treatment period (baseline test), one day after treatment period (the 1st postreatment test) and 35 days after treatment period (the 2nd posttreatment test). Results: Compared with the control group, the peak systolic velocity (PSV) and end diastolic velocity (EDV) of short posterior ciliary artery (SPCA) of the treatment eye group were relatively increased significantly in the 1st posttreatment test (P=0.017, 0.028), the PSV of SPCA of the opposite eye group was relatively increased significantly in the 1st posttreatment test (P=0.049), the EDV of central retinal artery (CRA) of the opposite eye group was relatively increased significantly in the 2nd posttreatment test (P=0.035). In contrast to the treatment eye group, the inferior quadrant RNFL thickness of the optic disc decreased significantly in the 2nd posttreatment test in the control group (P=0.009), the 6 o'clock RNFL thicknesses of the optic disc decreased significantly in the 1st posttreatment test in the control group (P=0.014), and the 6 o'clock and 7 o'clock RNFL thicknesses of the optic disc decreased significantly in the 2nd posttreatment test in the control group (F=0.029, 0.011). Conclusions: The application of compound anisodine for the treatment of primary glaucoma relatively increases the PSV and EDV of SPCA.
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The Heidelberg retinal tomography (HRT) is a technique that has been used for more than 20 years for glaucoma diagnostics and management. Many hundreds of scientific investigations have tested the reliability and accuracy of HRT for the early diagnosis of glaucoma and just as many studies can be found on the detection of progression in glaucoma. It is still one of the leading imaging systems for the detection and follow-up of glaucoma. Hardware and statistical methods implemented for progression detection have been regularly updated by the company and internationally known glaucoma specialists. Besides the analysis of stereometric parameters and trend analyses, the primary method for assessing glaucomatous change using the HRT is the topographic change analysis (TCA), a technique that compares the variability within a baseline examination to that between baseline and follow-up examinations.Furthermore, the flicker comparison enables detection of small topographic changes over time. The use of HRT does not replace clinical examinations but facilitates the assessment and management of glaucoma depending on observer experience. This imaging method will still have a significant value in the future for glaucoma diagnostics, with a special emphasis on assessment of progression.
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Purpose: To determine whether baseline Heidelberg Retina Tomograph (HRT) measurements of the optic disc are associated with the development of open-angle glaucoma (OAG) in individuals with ocular hypertension in the European Glaucoma Prevention Study (EGPS). Design: Retrospective analysis of a prospective, randomized, multicenter, double-masked, controlled clinical trial. Methods: There were 489 participants in the HRT Ancillary Study to the EGPS. Each baseline HRT parameter was assessed in univariate and multivariate proportional hazards models to determine its association with the development of OAG. Proportional hazards models were used to identify HRT variables that predicted which participants in the EGPS had developed OAG. Development of OAG was based on visual field and/or optic disc changes. Results: At a median follow-up time of about 5 years, 61 participants developed OAG. In multivariate analyses, adjusting for randomization arm, age, baseline IOP, central corneal thickness, pattern standard deviation, and HRT disc area, the following HRT parameters were associated with the development of OAG: the "outside normal limits" classification of the Frederick Mikelberg (FSM) discriminant function (hazard ratio [HR] 2.51, 95% confidence interval [CI]: 1.45-4.35), larger mean cup depth (HR 1.64, 95% CI: 1.21-2.23), cup-to-disc area ratio (HR 1.43, 95% CI: 1.14-1.80), linear cup-to-disc ratio (HR 1.43, 95% CI: 1.13-1.80), cup area (HR 1.33, 95% CI: 1.08-1.64), smaller rim area (HR 1.33, 95% CI: 1.07-1.64), larger cup volume (HR 1.30, 95% CI: 1.05-1.61), smaller rim volume (HR 1.25, 95% CI: 1.01-1.54), larger maximum cup depth (HR 1.18, 95% CI: 1.01-1.36), and cup shape measure (HR 1.18, 95% CI: 1.01-1.36). Conclusions: Several baseline HRT parameters, alone or in combination with baseline clinical and demographic factors, were significantly associated with the development of OAG among the EGPS participants.
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To examine the detection rates, specificity, and agreement between visual field (VF) progression and Heidelberg Retina Tomograph (HRT; Heidelberg Engineering, GmbH, Heidelberg, Germany) rim area (RA) progression in subjects with ocular hypertension (OHT). One hundred ninety-eight OHT and 21 control subjects were examined prospectively (1994-2001) with regular Humphrey VF (Carl Zeiss Meditec, Inc., Dublin, CA) and HRT testing. Point-wise linear regression (PLR) of sensitivity/time was used to assess VF progression, using standard and three-omitting (less stringent and stringent) criteria. The change in HRT-detected progression was assessed by linear regression of sectoral RA/time, defined as slope>1%/year, with significance level tailored according to series variability. Less stringent and stringent criteria were tested. Specificity was estimated by the proportions of control subjects with disease progression and significantly improving subjects (all). Agreement between disc and field progression in the subjects with OHT was assessed with specificities matched for both VF and HRT. Specificity for VF PLR was estimated to be 85.7% to 95.4% when standard criteria were used, and for RA/time to be 88.1% to 90.5% with the less-stringent criteria. In this comparison, 21.2% progressed by RA alone and 20.2% by VF alone, and 12.1% progressed by both RA and VF. Specificity was estimated to be 95.2% to 98.2% for both VF PLR and RA/time, using the three-omitting criteria and the stringent RA/time criteria, respectively. In this comparison, 8.6% progressed by RA alone, 15.1% by VF alone, and 3.5% by both RA and VF. A relatively high frequency of detected disease progression was observed with either method, with progression by VF occurring at least as frequently as progression by RA. Poor agreement between RA and VF progression was observed regardless of the specificity of the progression criteria. The results indicate that, in patients with ocular hypertension, monitoring of both VF and optic disc is necessary, as agreement between optic disc and VF progression is the exception rather than the rule.
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To compare the abilities of a new Glaucoma Probability Scoring (GPS) system and Moorfields regression analysis (MRA) to differentiate between glaucomatous and normal eyes using Heidelberg retinal tomograph (HRT)-III software and race-specific databases. In this prospective study, one eye (refractive error < or =5 D) each of consecutive normal patients and those with glaucoma was enrolled. All patients underwent a full eye examination, standard achromatic perimetry (Swedish Interactive Threshold Algorithm-standard automated perimetry (SITA-SAP), program 24-2) and confocal scanning laser ophthalmoscopy (HRT-II) within 1 month. Normal patients had two normal visual fields in both eyes (pattern standard deviation (PSD) >5% and Glaucoma Hemifield Test within 97% normal limits) and a normal clinical examination. Glaucoma was defined on the basis of SITA-SAP visual field loss (PSD<5% or Glaucoma Hemifield Test outside normal limits) on two consecutive visual fields. HRT-II examinations were exported to the HRT-III software (V.3.0), which uses an enlarged race-specific database, consisting of 733 eyes of white people and 215 eyes of black people. Race-adjusted MRA for the most abnormal sector (operator-dependent contour line placement) was compared with the global race-adjusted GPS (operator independent). MRA sectors outside the 99.9% confidence interval limits (outside normal limits) and GPS > or =0.64 were considered abnormal. 136 normal patients (72 black and 64 white patients) and 84 patients with glaucoma (52 black and 32 white patients) were enrolled (mean age 50.4 (SD 14.4) years). The average visual field mean deviation was (-)0.4 (SD 1.1) db for the normal group and (-)7.3 (SD 6.7) db for the glaucoma group (p<0.001). Mean GPS values were 0.21 (SD 0.23) and 0.73 (SD 0.27) for normal and glaucomatous eyes, respectively (p<0.001). Sensitivity and specificity values were 77.1% and 90.3% for GPS, and 71.4% and 91.9% for MRA, respectively. In this cohort, GPS software sensitivity and specificity values are similar to those of MRA, which requires placement of an operator-dependent contour line. The development of software to detect glaucoma without a contour line is critical to improving the potential use of HRT as a tool for glaucoma detection and screening.
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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.
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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.
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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.
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To assess whether baseline Glaucoma Probability Score (GPS; HRT-3; Heidelberg Engineering, Dossenheim, Germany) results are predictive of progression in patients with suspected glaucoma. The GPS is a new feature of the confocal scanning laser ophthalmoscope that generates an operator-independent, three-dimensional model of the optic nerve head and gives a score for the probability that this model is consistent with glaucomatous damage. The study included 223 patients with suspected glaucoma during an average follow-up of 63.3 months. Included subjects had a suspect optic disc appearance and/or elevated intraocular pressure, but normal visual fields. Conversion was defined as development of either repeatable abnormal visual fields or glaucomatous deterioration in the appearance of the optic disc during the study period. The association between baseline GPS and conversion was investigated by Cox regression models. Fifty-four (24.2%) eyes converted. In multivariate models, both higher values of GPS global and subjective stereophotograph assessment (larger cup-disc ratio and glaucomatous grading) were predictive of conversion: adjusted hazard ratios (95% CI): 1.31 (1.15-1.50) per 0.1 higher global GPS, 1.34 (1.12-1.62) per 0.1 higher CDR, and 2.34 (1.22-4.47) for abnormal grading, respectively. No significant differences (P > 0.05 for all comparisons) were found between the c-index values (equivalent to area under ROC curve) for the multivariate models (0.732, 0.705, and 0.699, respectively). GPS values were predictive of conversion in our population of patients with suspected glaucoma. Further, they performed as well as subjective assessment of the optic disc. These results suggest that GPS could potentially replace stereophotograph as a tool for estimating the likelihood of conversion to glaucoma.
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PurposeThis study aimed to define the confocal laser scanning ophthalmoscope (Heidelberg Retina Tomograph [HRT]) parameters that best separate patients with early glaucoma from normal subjects.
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Laser scanning tomography has been shown to be an accurate and reliable method for the assessment of the three-dimensional optic disc topography. The authors investigate the reliability of morphometric measurements with the Heidelberg retina tomograph, a new instrument which was designed based on this technology, which simplifies handling and is much smaller than the laser tomographic scanner. Three independent measurements of the optic disc were performed in 39 eyes of 39 patients which were equally divided into the following three groups: glaucoma, glaucoma suspects, and controls. The mean coefficient of variation for measurement in the glaucoma, glaucoma suspect, and control groups was 2.9%, 5.0%, and 3.4%, respectively, for cup area; 4.9%, 4.6%, and 4.6%, respectively, for cup volume; 5.2%, 3.8% and 3.3%, respectively, for mean cup depth; and 5.2%, 4.1%, and 4.0%, respectively, for maximal cup depth. The mean standard deviation for one pixel of the total image was 30 +/- 6 microns, 28 +/- 7 microns, and 22 +/- 6 microns for the three groups, respectively. The Heidelberg retina tomograph enables fast and reliable measurement of the optic disc topography and therefore may allow exact follow-up of patients.
Article
This study aimed to define the confocal laser scanning ophthalmoscope (Heidelberg Retina Tomograph [HRT]) parameters that best separate patients with early glaucoma from normal subjects. A cross-sectional study. A total of 80 normal subjects and 51 patients with early glaucoma participated (average visual field mean deviation = -3.6 dB). Imaging of the optic nerve head with the HRT and analysis using software version 1.11 were performed. The relation between neuroretinal rim area and optic disc area, and cup-disc area ratio and optic disc area, was defined by linear regression of data derived from the normal subjects. The normal ranges for these two parameters were defined by the 99% prediction intervals of the linear regression between the parameter and optic disc area, for the whole disc, and for each of the predefined segments. Normal subjects and patients were labeled as abnormal if the parameter for either the whole disc or any of the predefined segments was outside the normal range. The sensitivity and specificity values of the method were calculated. The highest specificity (96.3%) and sensitivity (84.3%) values to separate normal subjects and those patients with early glaucoma were obtained using the 99% prediction interval from the linear regression between the optic disc area and the log of the neuroretinal rim area. Similar specificity (97.5%) and lower sensitivity (74.5%) values were obtained with the 99% prediction interval derived from regression between the disc area and cup-disc area ratios. Poor separation between groups was obtained with the other parameters. The HRT, using the technique of linear regression to account for the relationship between optic disc size and rim area or cup-disc area ratio, provides good separation between control subjects and patients with early glaucoma in this population.
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To classify images of optic nerve head (ONH) topography obtained by scanning laser ophthalmoscopy as normal or glaucomatous without prior manual outlining of the optic disc. The shape of the ONH was modeled by a smooth two-dimensional surface with a shape described by 10 free parameters. Parameters were adjusted by least-squares fitting to give the best fit of the model to the image. These parameters, plus others derived from the image using the model as a basis, were used to discriminate between normal and abnormal images. The method was tested by applying it to ONH topography images, obtained with the Heidelberg Retina Tomograph, from 100 normal volunteers and 100 patients with glaucomatous visual field damage. Many of the parameters derived from the fits differed significantly between normal and glaucomatous ONH images. They included the degree of surface curvature of the disc region surrounding the cup, the steepness of the cup walls, the goodness-of-fit of the model to the image in the cup region, and measures of cup width and cup depth. The statistics of the parameters were analyzed and were used to construct a classifier that gave the probability, P(G), that each image came from the glaucoma population. Images were classified as abnormal if P(G) > 0.5. The probabilities assigned to each image were in most cases close to 0 (normal) or 1 (abnormal). Eighty-seven percent of the sample was confidently classified with P(G) < 0.3 or P(G) > 0.7. Within this group, the overall classification accuracy was 92%. The overall accuracy of the method (the mean of sensitivity and specificity, which were similar) in the whole sample was 89%. ONH images can be classified objectively and dependably by an automated procedure that does not require prior manual outlining of disc boundaries.
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To establish the anatomical relationship between visual field test points in the Humphrey 24-2 test pattern and regions of the optic nerve head (ONH) DESIGN: Cross-sectional study. Glaucoma patients and suspects from the Normal Tension Glaucoma Clinic at Moorfields Eye Hospital. Sixty-nine retinal nerve fiber layer (RNFL) photographs with well-defined RNFL defects and/or prominent bundles were digitized. An appropriately scaled Humphrey 24-2 visual field grid and an ONH reference circle, divided into 30 degrees sectors, were generated digitally. These were superimposed onto the RNFL images. The relationship of visual field test points to the circumference of the ONH was estimated by noting the proximity of test points to RNFL defects and/or prominent bundles. The position of the ONH in relation to the fovea was also noted. The sector at the ONH corresponding to each visual field test point, the position of the ONH in relation to the fovea, and the effect of the latter on the former. A median 22 (range, 4-58), of a possible 69, ONH positions were assigned to each visual field test point. The standard deviation of estimations was 7.2 degrees. The position of the ONH was 15.5 degrees (standard deviation 0.9 degrees ) nasal and 1.9 degrees (standard deviation 1.0 degrees ) above the fovea. The location of the ONH had a significant effect on the corresponding position at the ONH for 28 of 52 visual field test points. A clinically useful map that relates visual field test points to regions of the ONH has been produced. The map will aid clinical evaluation of glaucoma patients and suspects, as well as form the basis for investigations of the relationship between retinal light sensitivity and ONH structure.
Article
To compare the specificity and sensitivity of several different methods for using pointwise linear regression (PLR) to detect progression (deterioration) in visual fields. First, theoretical results were derived to predict which of the considered PLR methods would be the most specific and hence the least sensitive. Then, a "Virtual Eye" simulation model was developed that simulates series of sensitivity readings for a point over time. The model adds normally distributed noise (estimated from published results) to the sensitivity at each point to produce a series of fields to be analyzed using each method. Stable and deteriorating eyes were simulated, with the latter defined to have a noise-free loss of 2 dB/y at a significant cluster of points over the series. The most sensitive method tested was to flag a visual field as progressing if it had a point that exhibited a statistically significant slope (at the 1% level) of at least -1 dB/y in the sensitivity. The most specific was a new "Three-Omitting" method that is being proposed, using two confirmation fields in a novel way. Current methods of using confirmation fields to verify a significant slope incorrectly flagged up to twice as many stable eyes as having progressing fields as did our new method. Using the new proposed PLR method is recommended in preference to current PLR methods in any applications when a high degree of specificity is the main priority.
Article
To study the test-retest variability of stereometric parameters on the Heidelberg Retina Tomograph II, a new clinical instrument for glaucoma management. In a cross-sectional study of 24 consecutive cases of glaucoma and 26 healthy subjects, Heidelberg Retina Tomograph II stereometric parameters from five consecutive images were obtained for one randomly selected eye of each subject. Test-retest variability was studied using three different statistical methods (coefficient of variance, intraclass correlation coefficient, and Cronbach alpha). The effect of age, diagnosis, linear cup/disc ratio, visual acuity, and refractive error on test-retest variability on HRT II was analyzed. The repeatability of Moorfields regression analysis and the baseline variability in the progression analysis software was also studied. Using coefficient of variance, intraclass correlation coefficient, and Cronbach alpha, the test-retest variability was found to be lowest for mean cup depth, cup area, cup/disc area ratio, vertical cup/disc ratio and rim/disc area ratio, in that order. Test-retest variability had a significant correlation with age (r = 0.33, P = 0.019) and visual acuity (r = -0.46, P = 0.005). Compared with eyes with astigmatism less than 1 D (mean coefficient of variance = 6.4 +/- 4.9), the test-retest variability was higher (P = 0.044) in eyes with astigmatism more than 1D (mean coefficient of variance = 20.0 +/- 22.6). Moorfields regression analysis was inconsistent in 52% cases. The average baseline change in progression analysis software was 0.076 +/- 0.081. The test-retest variability of Heidelberg Retina Tomograph II stereometric parameters is comparable to that reported for the Heidelberg Retina Tomograph. Eyes with uncorrected astigmatism more than 1 D and poor visual acuity may have a higher variability of Heidelberg Retina Tomograph II stereometric parameters.
Article
To determine whether treatment with betaxolol can delay or prevent the conversion from ocular hypertension to early glaucoma on the basis of visual field criteria, by means of a prospective, randomised, placebo-controlled trial. Three hundred and fifty-six ocular hypertensives were randomized to treatment with either betaxolol drops or placebo drops during the period 1992-1996. Each patient was followed prospectively with 4-monthly visits. Examination at each visit included visual field testing, intra-ocular pressure (IOP) measurement and optic disc imaging. Conversion to early glaucoma was defined on the basis of visual field change by AGIS criteria. An intent-to-treat analysis compared visual field conversion after 3 years in the treatment and placebo arms. Normal visual field survival analysis was also performed. The IOP characteristics of the two treatment groups were compared. Two hundred and fifty-five patients completed the study, which ended in 1998, with a range of follow-up of 2-6 years. Sixteen (13.2%) of 121 patients in the placebo group converted to glaucoma, compared with 12 (9.0%) of 134 patients in the betaxolol group. The intent-to-treat analysis demonstrated no evidence of any difference in conversion rates between the betaxolol and placebo groups after 3 years. Visual field survival analysis demonstrated no significant difference between the betaxolol and placebo groups. The betaxolol-treated group had significantly lower post-treatment IOP values. Converters had significantly higher pre- and post-treatment IOP values than non-converters. Betaxolol significantly lowered the IOP level compared with placebo. Conversion to glaucoma was found to be related to both the baseline and post-treatment IOP levels. However the intent-to-treat analysis did not demonstrate a statistically significant reduction in the conversion rate in the betaxolol-treated group.
Article
The nature and mode of functional and structural progression in open-angle glaucoma is a subject of considerable debate in the literature. While there is a traditionally held viewpoint that optic disc and/or nerve fibre layer changes precede visual field changes, there is surprisingly little published evidence from well-controlled prospective studies in this area, specifically with modern perimetric and imaging techniques. In this paper, we report on clinical data from both glaucoma patients and normal controls collected prospectively over several years, to address the relationship between visual field and optic disc changes in glaucoma using standard automated perimetry (SAP), high-pass resolution perimetry (HRP) and confocal scanning laser tomography (CSLT). We use several methods of analysis of longitudinal data and describe a new technique called "evidence of change" analysis which facilitates comparison between different tests. We demonstrate that current clinical indicators of visual function (SAP and HRP) and measures of optic disc structure (CSLT) provide largely independent measures of progression. We discuss the reasons for these findings as well as several methodological issues that pose challenges to elucidating the true structure-function relationship in glaucoma.
Article
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.
Article
To evaluate the usefulness of the glaucoma probability score (GPS), which does not require manual outlining of the disc boundaries, and the Moorfields regression classification (MRA), which requires manual outlining of the disc boundaries, for discriminating between healthy and glaucomatous eyes, using the Heidelberg Retina Tomograph. Cross-sectional study. We prospectively selected 71 consecutive healthy subjects and 115 consecutive patients with open-angle glaucoma. Participants were divided into 2 groups depending on the results of standard automated perimetry and intraocular pressure. All participants underwent imaging of the optic nerve head with the Heidelberg Retina Tomograph 3. All tests were performed within 1 month of each subject's date of enrollment into the study by examiners masked to the other findings. The sensitivity and specificity of all parameters of the MRA and GPS classifications were calculated. The diagnostic accuracy at different severities of glaucoma and optic disc sizes was also evaluated. Receiver operating characteristic curves were plotted for the GPS values. The MRA global classification had a sensitivity of 73.9% and a specificity of 91.5%. The GPS global classification had a sensitivity of 58.2% and a specificity of 94.4%. The GPS had slightly higher sensitivity and somewhat lower specificity than the MRA when there was mild damage indicated by visual field tests. The MRA had the best discrimination capability for moderate and severe glaucoma. Both the GPS and MRA had lower sensitivity and higher specificity for small optic discs (<1.7 mm2) compared with medium and large discs. In general, the diagnostic performance of the GPS was similar to that of the MRA. The diagnostic accuracy of both classifications depends on the optic disc size and the glaucoma severity.
Article
Provides an update on research on Heidelberg retina tomograph (HRT) imaging of the optic nerve head in glaucoma. Particular reference is made to work assessing recently introduced software developments. Three main areas of investigation are covered: new developments in the third major revision of the HRT operational software (HRT-3), HRT's ability to correctly classify glaucomatous optic neuropathy, and HRT's role in monitoring disease progression. The software now incorporates a larger normative database of white patients as well as new ethnic-specific databases. The main classification tools in the new software are the Moorfields regression analysis and Glaucoma Probability Score. The performance of these classification systems is influenced by the new normative databases. A number of HRT rim area progression strategies has been proposed. These appear to complement visual field progression analyses, identifying a largely different subset of progressing patients. HRT measurement variability has recently been better characterized, and promising methods of improving measurement repeatability have been described. The HRT is a promising tool for monitoring patients with, or at risk of, glaucoma, although the relationship between progressive structural and visual field change has yet to be fully elucidated. Each refinement to the instrument software requires evaluation to establish whether it constitutes an improvement in our ability to manage patients.
Article
To investigate and compare the diagnostic accuracy of the Heidelberg Retinal Tomograph 3 (HRT3) diagnostic algorithms and establish whether they are affected by optic disc size and glaucoma severity. Multicenter cross-sectional evaluation of diagnostic tests. Two hundred forty-two eyes from 139 normal subjects and 103 glaucomatous patients classified by the presence of a repeatable visual field (VF) defect. Eyes were imaged by the HRT3. The diagnostic accuracies of Moorfields regression analysis (MRA) and the glaucoma probability score (GPS) was explored by sensitivity and specificity and area under the receiver operating characteristics curves (AUC). The analysis was performed globally and by optic disc size quartiles and by 3 VF severity groups. Sensitivity, specificity, and AUC. The GPS showed a sensitivity (80% vs. 77%) similar to and a specificity (57% vs. 67%) lower than that of MRA Result. It showed a higher specificity in small discs than MRA Result (77% vs. 68%) but a low to very low specificity in medium to very large discs (medium, 61%; large, 50%; very large, 26%). Moorfields regression analysis Global showed the highest sensitivity and specificity (68% and 78%) in very large discs. R. Burke linear discriminant function (RB-LDF) and cup shape measure (CSM) showed the best and least variable AUC across optic nerve head sizes and glaucoma stages. The sensitivity of both MRA and the GPS decreased at the earlier glaucoma stages. The MRA and GPS agreement was moderate throughout the entire population and in small discs and early stage, whereas it was weaker among the other disc size and glaucoma stage subgroups. HRT3 diagnostic algorithms' accuracy is moderate. The GPS is less specific and more influenced by disc size than MRA. Cup shape measure and the RB-LDF offer the best and less variable performances across different disc sizes and glaucoma stages.