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Test-Retest Variability of Topographic Measurements With Confocal Scanning Laser Tomography in Patients With Glaucoma and Control Subjects
Abstract
Using confocal scanning laser tomography, we studied the test-retest variability of topographic measurements of the optic nerve head and parapapillary retina in 30 patients with glaucoma and 30 normal control subjects. We obtained three independent images, separated by between one and six hours, centered on the optic nerve head. We condensed each original 256 x 256-pixel image to a 64 x 64-pixel image, thereby allowing a realistic estimate of the empiric 90% confidence interval of testretest variability at each condensed pixel. Confidence interval maps generated for each subject showed highest measurement variability along the cup border and blood vessels. The mean standard deviation equivalents of test-retest variability in the patients and controls were 31.20 and 25.94 microns, respectively. These differences were statistically significant (P = .010). Variability increased with age (P < .001). When the analysis was repeated for discrete parapapillary areas, the group differences were not statistically significant (P = .100).
... Tomograph (HRT, Heidelberg Engineering, Heidelberg, Germany) is the more widely used type of SLO used in both research and clinical settings. The methodology of the technique will be discussed in detail (Chauhan, et al., 1994, Rohrschneider, et al., 1993 .The HRT acquires 32 equally spaced confocal images along the 'Z' axis that is perpendicular to the optical axis, and has an image resolution of 256 X 256 pixels. Scan areas can be set to 10 X 10 degrees, 15X15 degrees, or 20 X 20 degrees, and the scan depth can be varied from 0.5 to 4.0mm. ...
... Chauhan et al. (Chauhan, et al., 1994) Cioffi et al. (Cioffi, et al., 1993) investigated the reproducibility of depth measurements in 30 normal eyes. 30 separate images of each optic nerve head were aligned and specific regions compared in each image. ...
... The Heidelberg Retina Tomograph is a type of confoeal scanning laser ophthalmoseope, developed by Heidelberg Engineering, Heidelberg, Germany, for the objeetive analysis of optic disc parameters. The system (Chauhan, 1994, Rohrschneider, 1994 uses eonfoeal optics comprising an imaging system with a known focal length and a detector located in a plane conjugate to the foeal plane of the imaging system. A low-power diagnostic helium-neon laser beam is scanned point-wise line by line across the fundus and optic nerve. ...
Background: The management of ocular hypertension (OHT) has considerable practical and financial implications for ophthalmology services in the U.K. Previous prophylactic treatment trials for OHT have so far been inconclusive (Kass, 1980, Epstein, 1989, Schulzer, 1991). New methods of detecting early glaucomatous damage are needed to identify ocular hypertensive patients at greatest risk of developing glaucoma, so that appropriate treatment may be targeted at those individuals. Objectives 1. To determine the effect of betaxolol on the conversion rate of OHT to early glaucoma. 2. To identify possible risk factors for conversion. 3. To evaluate methods of early detection of glaucoma, as compared to gold-standard methods. Methods: 356 ocular hypertensives were randomised to treatment with betaxolol drops or placebo, and followed 4 monthly for 2-6 years with visual field testing, intra-ocular pressure (IOP) measurement and optic disc and retinal nerve fibre layer (RNFL) imaging. Conversion was defined using visual field criteria. Results: 1. No overall protective effect of betaxolol against conversion was found as compared to placebo. 2. The converters had significantly higher pre-and post-treatment IOPs than the group of non-converters. Betaxolol had a smaller hypotensive effect on the mean pre-treatment IOP level of the converters. 3. Sequential HRT analysis demonstrated glaucomatous optic disc change, prior to reproducible visual field change in the converters. Some non-converters demonstrated optic disc change despite maintaining normal visual fields. Conclusions: Betaxolol did not affect the conversion rate as compared to placebo, despite having a statistically significant IOP lowering effect. Higher IOP levels are a risk factor for conversion. Betaxolol appeared to have a smaller hypotensive effect in the converting group, and it is possible that these less responsive patients are therefore at greater risk of conversion. The HRT is a useful tool for the early detection of glaucomatous optic disc damage and may identify patients at risk of developing visual field loss.
... Lusky et al (1993) reported that the mean pixel SD in ten normal eyes was 30.1pm. Chauhan et al (1994) reported that the SD of pixel heights in clusters was 25.9pm. CiofFi et al (1993) used a Zeiss prototype scanning laser tomograph and found that the pooled confidence interval for pixel variability over 30 images in 19 normal eyes was 102pm (equivalent SD about 50pm). ...
... Many investigators have found higher pixel height variability over the optic nerve head, especially in the region of the cup edge, compared with over flatter peripapillary retina. High variability has been associated with steep contours in topography such as at the cup edge and over blood vessels Chauhan et al, 1994;Cioffi et al, 1993;Brigatti et al, 1995). ...
... Studies report that pixel height variability tends to be higher in glaucoma than in normal eyes, although most have not found differences to be statistically significant Cioffi et al, 1993;Brigatti et al, 1995). Only Chauhan et al (1994) found that glaucoma eyes had significantly more variability than normal eyes (p=0.01). They pooled pixels into clusters of 'superpixels' and found that variability was significantly more in glaucoma than normal eyes over the optic nerve head but not peripapillary retina, possibly because glaucomatous cups are steeper. ...
Analysis of sequential scanning laser tomography of the optic nerve head must be able to tell disease-induced change from measurement variability if it is to be useful for identifying glaucoma progression. Variability in neuroretinal rim area measurement was found to differ between optic nerves and between regions within each nerve, and was influenced by glaucomatous morphology, varying test conditions and different reference planes. Up to 95% of this variability could be explained by fluctuation in the height between the nerve surface and reference plane, and of the nerve head's centre of gravity along the z-axis. Such fluctuation, whether due to image variability or progressive disease, affects the position of conventional reference planes and limits their usefulness as absolute measures of change. A novel reference plane was designed that is customised to each optic nerve head, lies at a depth compatible with least variability, and stays in position despite glaucomatous damage. Its position in any nerve is calculated from surface height at the nerve margin in multiple topography images, and kept constant throughout each image series. It was found that the reference plane's description of neuroretinal rim was more reproducible and corresponded more closely with actual rim appearance compared with conventional reference planes. An analytical approach was devised to identify change based on this new reference plane. Variability in each 30degree sector of rim area in each nerve was estimated by modelling variability within images from all time-points of any nerve's image series. Confidence limits of variability represented variability in each sector, and only change repeatedly exceeding these limits in two of three tests was attributed to disease. Assessed by 90% and 95% limits of variability, progression was identified with a sensitivity and false positive rate of 90% and 6%, and 83% and 3% respectively in ocular hypertension converter eyes with unambiguous glaucomatous visual field change and unchanging eyes of normal controls. When tested in various presentations of suspected and manifest normal-pressure and high-pressure glaucoma, progression was detected in glaucoma suspect eyes without visual field defects, eyes that progressed to develop field defects, and eyes with established and more severe glaucoma.
... Though the technology has been shown to be accurate and to obtain reproducible topography images of the ONH (Chauhan et al., 1994, Rohrschneider et al., 1994, images can be prone to artefacts and noise from a number of sources. These include eye movements, temporary deformations of the ONH, cataract and pupil size. ...
... The CLST, as typified by the HRT, has been shown to give a repeatable measure of optic disc structure , Cioffi et al., 1993, Chauhan et al., 1994. The ...
... Previous studies have used the MPHSD as a metric to evaluate the repeatability of the technology in normal subjects and glaucoma patients (Chauhan et al., 1994, Rohrschneider et al., 1994. Most previous studies of detection of glaucoma in HRT images have used this metric as a criterion in selection of data for analysis. ...
... A further description of the technology is provided by Zinser, Wijnaendts-van-Resandt et al, 1989;Chauhan, 1996. The technology has been shown to obtain reproducible topography images of the ONH (Chauhan, LeBlanc et al, 1994;Rohrschneider, Burk et al, 1994). The repeatability of topography images is typically quantified using mean pixel height standard deviation (MPHSD). ...
... The real promise of the HRT may lie in objectively measuring progressive structural damage, or stability, in patients being followed over time. This is possible because the local height measurements at each of the pixels of a topography image are sufficiently reproducible (Chauhan, LeBlanc et al, 1994;Rohrschneider, Burk et al, 1994). However, to date research in this area has used stereometric parameters, summary measures of the ONH, to detect change. ...
... Previous studies have used this metric to evaluate the repeatability of the technology in normal subjects and glaucoma patients (Chauhan, LeBlanc et al, 1994;Rohrschneider, Burk et al, 1994). It has been show that MPHSD is influenced by lens opacity, age and degree of astigmatism . ...
... The MRA and the Glaucoma Probability Score (GPS) [Swindale et al., 2000], were incorporated into the Heidelberg Retina Tomograph (HRT), resulting in a more sophisticated version of this instrument. Both instruments achieve high reproducibility of measurement data [Rohrschneider et al., 1994;Chauhan et al., 1994;Dreher et al., 1991;Rohrschneider et al., 1993]. Fig. 1.10 and Fig. 1.11, show the usefulness of this method to distinguish between normal discs and early glaucomatous changes. ...
... Change in both modalities may occur, though not always identified at the same time within the relatively short time span of typical longitudinal studies. One explanation for this dissociation is that VF sensitivity, optic nerve head (ONH) topographic parameters, and RNFLT measurements all are affected by measurement variability [Artes et al., 2002;Tan et al., 2003;Budenz et al., 2008;Ortega et al., 2007;Strouthidis et al., 2005;Owen et al., 2006;Lusky et al., 1993;Chauhan et al., 1994;Mikelberg et al., 1993;Heijl et al., 1989Heijl et al., , 1987Henson et al., 2000], which may confound attempts to identify progression when it is present. Structural changes not linked directly to RGC loss, such as conformational changes in the lamina cribrosa or in glial support tissue, and changes in function not linked directly to RGC loss, such as the development of media opacity or RGC dysfunction, are further possible explanations for structure-function dissociation. ...
Glaucoma is the leading cause of irreversible blindness worldwide. It is a progressive optic neuropathy in which retinal ganglion cell (RGC) axon loss, probably as a consequence of damage at the optic disc, causes a loss of vision, predominantly affecting the mid-peripheral visual field (VF). Glaucoma results in a decrease in vision-related quality of life and, therefore, early detection and evaluation of disease progression rates is crucial in order to assess the risk of functional impairment and to establish sound treatment strategies. The aim of my research is to improve glaucoma diagnosis by enhancing state of the art analyses of glaucoma clinical trial outcomes using advanced analytical methods. This knowledge would also help better design and analyse clinical trials, providing evidence for re-evaluating existing medications, facilitating diagnosis and suggesting novel disease management. To facilitate my objective methodology, this thesis provides the following contributions: (i) I developed deep learning-based super-resolution (SR) techniques for optical coherence tomography (OCT) image enhancement and demonstrated that using super-resolved images improves the statistical power of clinical trials, (ii) I developed a deep learning algorithm for segmentation of retinal OCT images, showing that the methodology consistently produces more accurate segmentations than state-of-the-art networks, (iii) I developed a deep learning framework for refining the relationship between structural and functional measurements and demonstrated that the mapping is significantly improved over previous techniques, iv) I developed a probabilistic method and demonstrated that glaucomatous disc haemorrhages are influenced by a possible systemic factor that makes both eyes bleed simultaneously. v) I recalculated VF slopes, using the retinal never fiber layer thickness (RNFLT) from the super-resolved OCT as a Bayesian prior and demonstrated that use of VF rates with the Bayesian prior as the outcome measure leads to a reduction in the sample size required to distinguish treatment arms in a clinical trial.
... Uprkos dobroj ukupnoj dijagnostičkoj sposobnosti [15] i dobroj reproducibilnosti [16] CSLO, ustanovilo se da značajan uticaj na preciznost u diskriminaciji normalnih od glaukomskih papila ima stadijum bolesti i veličina papile, pri čemu je niža senzitivnost u ranim stadijumima bolesti i kod papila manje površine, a niža specifičnost kod većih papila [17][18][19]. ...
... Kada je u pitanju statistička analiza GPS, vrijednosti AUC su za numerički glaucoma probability bile izvrsne, odnosno od 0,92-0,95, što ga svrstava u visoko značajan parametar za diskriminaciju očiju sa glaukomom od zdravih očiju. Slično je i kod drugih studija [14][15][16]23]. ...
Uvod. Lokalizovani defekti retinalnog sloja nervnih vlakana (retinal nervefibre layer, RNFL) najčešće se javljaju u ranom glaukomu sa učestalošću oko20%. Heidelberg Retina Tomograf (HRT 3) je konfokalna skening laser oftalmoskopijadizajnirana kako bi olakšala objektivnu i kvantitativnu procjenupapile i RNFL. Cilj rada je bio da ispitamo dijagnostičku mogućnost HRT 3da razdvoji zdrave od očiju sa glaukomom i sa prisutnim lokalizovanim defektimaRNFL i, da ustanovimo kako je stadijum oboljenja uticao na njegovudijagnostičku sposobnost.Metode. Statistički su analizirani podaci dobijeni pregledom HRT 3 i red-freefotografijom fundusa 12 očiju sa glaukomom sa prisutnim lokalizovanimdefektima RNFL i 14 očiju zdravih ispitanika kontrolne grupe.Rezultati. Mjera oblika ekskavacije (Cup Shape Measure, CSM) je parametarkoji je pokazao najveću dijagnostičku preciznost kako globalno (AUC:0,88) tako i u sektorima javljanja lokalizovanih defekata RNFL (AUC: 0,85),odnosno temporo-superiorno i temporo-inferiorno. U ranom i umjerenomstadiju bolesti, skor vjerovatnoće glaukoma (Glaucoma Probability Score, GPS)se pokazao kao sposobniji od Moorfields-ove analize regresije (MoorfieldsRegression Analysis, MRA) da razdvoji oči sa glaukomom i lokalizovanimdefektima RNFL od zdravih i to sa relativno visokom senzitivnošću (83% i78%) u sektorima u kojima su bili prisutni lokalizovani defekti RNFL verifikovanired-free fotografijom fundusa. Analiza RNFL prikazana na izvještajuHRT 3 kao grafikon RNFL profila se pokazala kao statistički značajna daukaže na prisustvo lokalizovanih defekata u odnosu na red-free fotografijupapile i RNFL.Zaključak. Konfokalna skening laser oftalmoskopija primijenjena kod pacijenatasa ranim i umjerenim stadijumom glaukoma i prisutnim lokalizovanimdefektima RNFL, pokazala se kao pouzdana za otkrivanje morfoloških promjena,a kao najbolji indikatori su se pokazali CSM i GPS.
... The sensitivity and specificity were found to be affected by reference height difference and image quality, the same factors that affect the measurement variability of the HRT [30]. There is variability of topographic measurements that can decrease the ability of the stereometric parameters to detect glaucomatous progression [31][32][33][34]. ...
... It is estimated that between 50% and 90% of cases of glaucoma in the community are undiagnosed at any point in time [37,68], so there has been interest in using the HRT as a screening device for glaucoma [15,[69][70][71]. Many studies have shown that HRT measurements are accurate and reproducible [31,[72][73][74], more so than measurements from clinical examination. ...
Confocal scanning laser ophthalmoscopy through the Heidelberg Retina Tomograph (HRT) provides a rapid, safe, noncontact, and noninvasive imaging of the optic disc in three-dimensions, and provides precise detailed information about the optic disc beyond that which the clinical exam can measure. The HRT I was developed for research purposes only and was not used clinically. The HRT II was developed to be user-friendly, more rapid, and was used as an adjunct to clinical examination in the detection and progression of glaucoma. One of the main pitfalls of the HRT II was that it was operator-dependent. The HRT III was developed to be operator-independent. Initially the Moorsfield Regression Analysis provided the analysis of the stereometric optic disc parameters. The Glaucoma Probability Score, given its ease of use, operator-independence, and rapidity of use, soon gained popularity. Numerous studies have compared these two methods of analysis, with the conclusion that the Glaucoma Probability Score provides a higher sensitivity and a lower specificity than the Moorsfield Regression Analysis, which may indicate that it has potential as a screening test for glaucoma. However, there is no consensus on the use of the Glaucoma Probability Score as a screening test for glaucoma. While HRT data may be useful as a clinical adjunct in the screening and diagnosis of glaucoma, it should ultimately only be used to support clinical examination.
... The loss in function can be measured by achromatic or blue on yellow perimetry, flicker perimetry, colour vision testing, and many other psychophysical strategies. 1 Most of the morphological alterations of the optic nerve head have been described semiquantitatively or qualitatively using the cup/ disc diameter ratio and qualitative variables such as the occurrence of disc haemorrhages and neuroretinal rim notches. 2 Since the introduction of confocal laser scanning tomography, new technology has made possible the semiautomatic quantification of the topography optic nerve head. [3][4][5][6][7][8] Using this technique, a whole array of new quantitative variables has become available to detect early changes of the optic disc. [9][10][11][12][13][14] In an eVort to increase the predictive value of the quantitative variables in diVerentiating normal eyes from eyes with early glaucomatous damage, mathematical equations combining various morphometric variables have been proposed to increase the ability to detect early morphological changes. ...
... The technique, including its reproducibility and reliability, has already been described in detail elsewhere. [3][4][5][6][7][8][9][10][11][12][13][14] The HRT variables were measured for the optic disc as a whole and in four separate disc sectors. The right angled superotemporal sector and the right angled inferotemporal sector were tilted 15 degrees temporal to the vertical optic disc axis. ...
AIM To evaluate and compare four different mathematical formulas for the early detection of morphometric optic nerve head changes in chronic open angle glaucoma. METHODS The optic nerve heads of 161 patients with perimetrically defined glaucomatous optic nerve damage and of 194 normal subjects were examined by confocal laser scanning tomography. Using four formulas of linear discriminant analysis and the optic cup shape measure as the single optic disc variable, the predictive power of each of these methods was examined to differentiate between the normal eyes and the glaucoma eyes. RESULTS The highest predictive power had an optic disc sector based formula, in particular in eyes with medium and large optic discs. This optic disc sector based formula was the one with the best agreement with the other formulas examined. It achieved a better predictability than any single optic disc variable evaluated. CONCLUSIONS Combining quantitative optic disc variables by discriminant analysis functions, the predictive power of semiautomatic quantitative optic nerve head evaluation can be improved by providing the ophthalmologist with a diagnostic score for the detection of glaucomatous optic nerve damage. Because of the pattern of glaucomatous neuroretinal rim loss, an optic disc sector based discriminant formula may have a higher diagnostic precision than other formulas in detecting early glaucomatous damage.
... Ophthalmoscopic estimation of cup-disk ratio is unreliably subjective [59,60] and has been superseded by advances in imaging technology. Structural characteristics of the optic nerve can be objectified using imaging modalities such as stereoscopic photography [61], confocal scanning laser ophthalmoscopy (cSLO) [62], scanning laser polarimetry (SLP) [63], and OCT [64]. Of these, the most widely used in current clinical practice is OCT, which has been quoted as having a sensitivity and specificity of 83 and 88%, respectively, for detecting significant RNFL abnormalities [65], in addition to good repeatability [66,67]. ...
Introduction: Increasing life expectancy and ageing populations across the world are causing the number of glaucoma patients to rise dramatically. With longer lifespans also comes the need to improve the timeframe and accuracy with which we can diagnose, monitor and treat patients, ensuring longevity of vision contributes to a meaningful quality of life. Current markers used in glaucoma practice are in many cases suboptimal in their ability to accurately identify glaucomatous damage in time to prevent irreversible optic neuropathy.
Areas covered: This review summarises the important properties of successful biomarkers and surrogates, and relates this to how intraocular pressure, visual field testing, and imaging have been refined to improve early diagnosis and progression analysis of glaucoma patients. Secondly, we discuss newer concepts in imaging, genetics, and quality of life measures which may provide biomarkers and surrogate endpoints with which to develop novel treatments in the future.
Expert Commentary: We summarise the key relevant points in glaucoma research, and the current techniques being trialled that are most likely to lead to valuable biomarkers for the future.
... Because of the reliability of the HRT-II, 21,22 we believed that objective determinations of the morphology of the optic disc obtained by HRT-II can be used to classify the optic discs into different morphological types. We hypothesized that the correlation coefficients between the optic disc parameters and the MD of the HFA will be higher when the parameters of the different types of optic disc morphology are individually assessed. ...
... The Heidelberg Retina Tomograph (HRT) provides rapid measurements of optic disc topography on a point-by-point basis, and calculates a variety of disc parameters 12 . The reproducibility and repeatability are reported to be good 13,14 . ...
... New imaging techniques are evolving to assess the state of the optic nerve head and RNFL quantitatively. Laser scanning tomography is an accurate and reproducible method that allows for three-dimensional optic disc analysis [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] . In this cross-sectional study, we address the question of whether the presence of functional damage from primary open-angle glaucoma (POAG), as documented by white-on-white perimetry, can be predicted by topometric parameters which describe the optic nerve head topography, independent of a clinical prejudgment of whether or not the optic disc shows structural glaucomatous alterations. ...
Purpose: To evaluate which reference plane-independent topometric optic disc parameters predict glaucomatous visual field defects (GVFD), irrespective of the appearance of the clinical optic nerve head. Patients and methods: Laser scanning tomography was used to analyze the topography of 136 optic discs, preclassified according to computed static white-on-white perimetry into a control group (C, n=78) with normal visual fields and a glaucoma group (G, n=58) with glaucomatous visual field defects (GVFD). A discriminant analysis, based upon 20 optic cup level reference plane-independent topometric variables, was used to evaluate the maximum classification rate with respect to perimetry. The three best separating variables which predict the presence of GVFD were identified by a stepwise discriminant analysis. Results: The maximum classification rate by a linear combination of 20 topometric variables resulted in a whole non-error rate of 82.4%; 112 of 136 visual field results were predicted correctly by optic disc topography (sensitivity 0.759, specificity 0.872). A robust L1 discriminant analysis of three of these topometric parameters predicted GVFD in 110 of 136 eyes at a whole non-error rate of 80.9% (sensitivity 0.741; specificity 0.859). The following parameters were selected: 1. The difference between the contour line mean height (CLM difference) in the temporal inferior octant and the temporal quadrant (TQ) of the optic disc (130±80 µm C; 40±110 µm G; p<0.0001). 2. The CLM difference between the temporal superior optic disc octant (TSO) and TQ (180±110 µm C; 80±110 µm G; p<0.0001). 3. The 'optic disc cup-steepness' (third moment of frequency distribution of optic cup depth readings) in the TSO of the optic disc (-0.02±0.13 C; 0.11±0.14 G; p<0.0001). Discussion: The results of this cross-sectional study indicate that static perimetry and quantitative three-dimensional optic disc analysis are supplementary tools in the assessment of structural and functional damage in primary open-angle glaucoma at a given stage of the disease. An objective optic disc classification, indicating the risk of existing functional damage as documented in w/w perimetry, may be based upon combinations of reference level independent three-dimensional topometric parameters.
... 81 Most studies investigating ONH morphology in normal and glaucomatous eyes have used confocal scanning laser ophthalmoscopy (CSLO) technology. Overall, measures from CLSO are repeatable [82][83][84] and provide valuable information for glaucoma diagnosis and management. [85][86][87] However, a significant drawback with CLSO is the stability of the reference plane, resulting in higher test-retest variability. ...
Purpose:
The purpose of this study was to determine the relationship between optical coherence tomography (OCT) measures of retinal nerve fiber layer (RNFL) and neuroretinal rim (NRR) in a nonhuman primate experimental glaucoma model, and in a population of clinical patients.
Methods:
For nonhuman primates, normative data were collected from 44 healthy monkeys, and nine animals with unilateral experimental glaucoma that were followed longitudinally. Cross-sectional human subjects data were collected from 89 healthy, 74 glaucoma suspects, and 104 glaucoma patients. Individualized transverse scaling for OCT scans was calculated using a schematic eye that incorporated optical ocular biometry. Custom algorithms were used to quantify RNFL thickness with and without vessels removed, scaled minimum rim width (sMRW), and neural rim volume (NRV).
Results:
For the experimental glaucoma group, NRR parameters showed the first changes with increased cumulative IOP. The data for both NRR and RNFL measures were best fit by an exponential rise model (NRV, R2=0.79, P<0.01, sMRW, R2=0.74, P<0.01). The major retinal vascular thickness contribution to the RNFL decreased (0.03 μm/μm, P<0.01) with RNFL loss, but the percent vascular contribution increased (-0.1%/μm, P<0.01) with disease progression. Overall, the findings for the cross-sectional human data were similar to those of the experimental model.
Conclusions:
The findings illustrate a nonlinear relationship between NRR and RNFL measures and provide support for the use of multiple OCT scaled morphological measures for the diagnosis and management of primary open angle glaucoma in humans.
... The instrument measurement variability could be due to the Poisson nature of the image formation in the CCD camera and also due to any illumination changes between follow-up exams. Pixel-level HRT height measurements were found to be reproducible for both normal and glaucoma patients with height variability <50 μm [65,66]. The pixel-level height variabilities were found to be higher in the region within the optic disc margin and also in the locations with a higher height gradient, such as blood vessels and topograph borders, compared to the height measurements in the peripapillary retina. ...
In this chapter, we present a brief overview of the anatomy of the eye and pathophysiology of glaucoma followed by a comprehensive review of the glaucoma literature in the context of detecting progression of glaucomatous structural defects in the optic nerve head (ONH) region of an eye. Confocal scanning laser ophthal- moscopes (CSLOs) are routinely used in clinical and laboratory research applica- tions in ophthalmology to capture the three-dimensional architecture of the ONH of a human eye in vivo and to generate reproducible ONH topographs of an eye. Because glaucoma is a progressive optic neuropathy, the structural changes associ- ated with a glaucomatous condition in an eye can be captured and analyzed using CSLOs. The CSLO-generated ONH topographs taken during baseline and follow- up visits can be used to detect and quantify the structural changes in the ONH region. We review the existing statistical and computational methods of detecting structural changes in the ONH region of an eye using global and regional ONH summary parameters (called stereometric parameters) and using pixel-level height measurements. Data sets of selected participants from the University of California San Diego (UCSD) Diagnostic Innovations in Glaucoma Study are used for demonstration. Section 7.1 provides a brief overview of the anatomy of the eye and pathophysiology of glaucoma. In Section 7.2, we discuss the general appearance of the ONH of a healthy eye and observable characteristic changes in the ONH region in eyes with glaucoma. A brief description of the principle of CSLOs and their use in examining the ONH region of an eye by acquiring ONH topographs is described in Section 7.3. In addition, methods of automatically estimating various ONH stereometric parameters using the Heidelberg Retina Tomograph (Heidelberg Engi- neering, Heidelberg, Germany), including the existing methods of locating the lower extents of the retinal nerve fiber layer using a reference plane, are presented in detail. In Section 7.4, we discuss in detail the existing methods of detecting change over time in the CSLO ONH topographs using their ONH stereometric parameters
... This result may be due in part that glaucoma eyes tend to have a higher standard deviation of the mean topography image than non-glaucomatous eyes. [34,35] However, including the standard deviation in the full model had almost no effect on the estimated rates of rim area change over time. It is possible that if we had included poor quality images, then we might expect more variability in the estimates of the stereometric parameters and a decreased likelihood that significant rates of change would be detected. ...
Purpose:
To compare rates of topographic change in ocular hypertensive eyes that develop primary open-angle glaucoma (POAG) compared to eyes that do not, and to identify factors that influence the rate of change.
Design:
Longitudinal, randomized clinical trial.
Methods:
Four hundred forty-one participants (832 eyes) in the Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the Ocular Hypertension Treatment Study were included. POAG was defined as repeatable visual field, photography-based optic disc changes, or both. The rate of topographic change in the 52 participants (66 eyes) who developed POAG was compared with that of participants who did not develop POAG using multivariable mixed effects models.
Results:
In both univariate and multivariate analyses, the rate of rim area loss was significantly faster in eyes in which POAG developed than in eyes in which it did not (univariate mean, -0.0131 mm(2)/year and -0.0026 mm(2)/year, respectively). The significantly faster rate of rim area loss in black persons found in the univariate analysis did not remain significant when baseline disc area was included in the model. In multivariate analyses, the rate of rim area loss and other topographic parameters also was significantly faster in eyes with worse baseline visual field pattern standard deviation and higher intraocular pressure during follow-up. Moreover, a significant rate of rim area loss was detected in eyes in which POAG did not develop (P < .0001). The rate of rim area loss in eyes with an optic disc POAG endpoint was significantly faster than in those with a visual field POAG endpoint.
Conclusions:
The rate of rim area loss is approximately 5 times faster in eyes in which POAG developed compared with eyes in which it did not. These results suggest that measuring the rate of structural change can provide important information for the clinical management of ocular hypertensive patients. Additional follow-up is needed to determine whether the statistically significant change in the eyes in which POAG did not develop represents normal aging or glaucomatous change not detected by conventional methods.
... [3][4][5] Change in both modalities may occur, though not always identified at the same time within the relatively short time span of typical longitudinal studies. One explanation for this dissociation is that VF sensitivity, optic nerve head (ONH) topographic parameters, and retinal nerve fiber layer (RNFL) thickness measurements all are affected by measurement variability, [6][7][8][9][10][11][12][13][14][15][16][17] which may confound attempts to identify progression when it is present. Structural changes not linked directly to retinal ganglion cell (RGC) loss, such as conformational changes in the lamina cribrosa or in glial support tissue, and changes in function not linked directly to RGC loss, such as the development of media opacity or RGC dysfunction, are further possible explanations for structure-function dissociation. ...
To assess whether neuroretinal rim area (RA) measurements of the optic disc could be used to improve the estimate of the rate of change in visual field (VF) mean sensitivity in patients with ocular hypertension (OHT) using a Bayesian linear regression (BLR), compared to a standard ordinary least squares linear regression (OLSLR) of mean sensitivity (MS) measurements alone.
MS and RA measurements were analyzed from a longitudinal series of 179 patients with OHT visiting Moorfields Eye Hospital between 1992 and 2000. For each patient, linear regression of RA was computed after an appropriate transformation to "scale" RA with MS measurements, and the slope coefficient from this regression was used as a prior for BLR of MS. The BLR then was compared with the OLSLR approach by evaluating how accurately each regression technique predicted future MS measurements.
On average, BLR was significantly more accurate than OLSLR for series up to 8 measurements long (root-mean-square prediction error [RMSPE] was 0.14 decibels [dB] smaller with BLR than OLSLR; P < 0.001, Wilcoxon signed-rank test), with OLSLR of VF data alone being more accurate for longer series (RMSPE was 0.06 dB smaller with OLSLR than BLR).
BLR provides a significantly more accurate estimate of the rate of change in MS than the standard OLSLR approach, especially in short time series, suggesting that structural measurements can be used successfully in statistical models to assist clinicians monitoring VF progression in patients with OHT. Further studies are necessary to validate the method in glaucoma patients.
... As it is reproducible and objective, confocal laser scanning tomography bears great promise to improve diagnostic decisions in glaucoma. Statistical methods have already resulted in previously unattainable precision in detecting change over time [5]. ...
This paper presents a series of experiments testing the feasibility of employing image-processing techniques for the feature extraction stage in the implementation of a basic optic nerve image classifier. Such a scheme completely removes the need for manually identifying the edge of the optic nerve. In this work, Zernike moments are extracted from Confocal Scanning Laser Tomography images of optic discs for the purposes of classifying the disc as healthy or damaged using a linear discriminant function derived from a linear perceptron. Our preliminary results, when compared with the performance of conventional feature sets, demonstrate the appropriateness of this approach.
... This has also been found in other studies. [43][44][45][46][47][48][49] Although identical LCDR values do not guarantee perfect disc-margin delineation, the agreement shows that any imperfections in the delineation do not compromise the diagnostic performance for this variable. Hence, disc-area adjusted LCDR appears to be the most suitable variable for an HRT3-based epidemiological definition of glaucomatous optic neuropathy. ...
To establish normative values for Heidelberg Retina Tomograph (HRT3) variables and to develop HRT3-based criteria for glaucomatous optic neuropathy for epidemiological research in a white population.
Consecutive participants in the Rotterdam Study were examined with HRT and simultaneous stereoscopic fundus photography (ImageNet) in addition to other ophthalmic examinations including intraocular pressure (IOP) measurements and perimetry. Normative values for all HRT3 variables were determined in participants who met all the following criteria: no glaucomatous visual field loss (GVFL), an IOP of 21mmHg or less, no IOP lowering treatment, and a negative family history of glaucoma. Sensitivity was determined in participants with glaucomatous visual field loss at a fixed high specificity of 97.5% - a value commonly used in population-based epidemiology.
A total of 2516 participants were included in this study of whom 66 had glaucomatous visual field loss in at least one eye and 1680 fulfilled the criteria for contributing to the normative values. The HRT3 linear cup-disc ratio (LCDR) variable, adjusted for disc area, showed the highest sensitivity, 35%, at the required specificity of 97.5%. The 97.5th percentile of the LCDR was 0.67 for small discs (up to 1.5 mm(2)), 0.71 [corrected] for medium-sized discs and 0.76 [corrected] for large discs (above 2.0 mm(2)).The HRT3 Glaucoma Probability Score and previously published linear discriminant functions showed a lower sensitivity than LCDR at this specificity.
At the high specificity of 97.5% as is commonly used in population-based epidemiology, the sensitivity of the HRT3 is low - albeit not lower than that of the vertical cup-disc ratio as assessed with simultaneous stereoscopic fundus photography and analyzed with the ImageNet software. The LCDR variable, stratified for disc area, seems to be the most suitable variable to develop criteria for glaucomatous optic neuropathy for epidemiological purposes.
Confocal scanning laser tomography is an imaging technique used for determining the topography of the optic nerve head and retina. Since images can be acquired through undilated pupils and analysed rapidly, the technique is particularly suited for clinical use. One of the largest potentials of scanning laser tomography is the detection of structural alterations in the optic nerve head and peripapillary retina caused by glaucoma. The ability to detect change depends on obtaining an accurate estimate of test-retest variability of regional measurements due to instrumental, computational and a host of physiological factors.
The nerve fiber layer (NFL), consisting of the axons of ganglion cells sweeping across the inner surface of the retina to the disc, transmits all the visual information from the eye to the brain. The normal, topographically regular pattern of nerve fibers is illustrated in Figure 1. Ophthalmoscopically, the nerve fiber layer is recognized as a pattern of subtle striations emanating from the disc a short distance; the striations are evidently bundles of axons contained within glial tunnels formed by Muller's cell processes ⁶ . Glaucoma and other optic neuropathies damage the nerve fibers and cause defects within the pattern. The bundles are fairly easy to see near the disc, and the circumpapillary nerve fibers have proved useful to image, because fiber damage and defects in the striation pattern sometimes precede detectable visual field defects. It has previously proved impossible, however, to image non-invasively the details of the perifoveally originating papillomacular bundles. Because the visual information from the perifoveal area is crucial to visual performance and because some neuropathies affect central vision preferentially (e.g., Leber's optic neuropathy), it may be useful to visualize the papillomacular bundle near the fovea, where a focal pattern of loss might be noticeable and well-correlated to focal visual deficits.
Both structural and functional parameters worsen with advancing glaucoma. The precise relationship between structure and function is variable at an individual level, but both are needed to fully quantify disease. The results of structural or functional tests should only be interpreted in context of other findings and after careful assessment of clinical risk for glaucoma. Methods for integrating structural and functional measures to facilitate evaluation of patients with glaucoma are likely to become available in the clinical setting in the next decade.
Purpose:
To characterize the rate and pattern of age-related and glaucomatous neuroretinal rim area changes in subjects of African and European descent.
Design:
Prospective longitudinal study.
Participants:
Two hundred ninety-six eyes of 157 healthy subjects (88 patients of African descent and 69 of European descent) and 73 progressing glaucoma eyes of 67 subjects (24 patients of African descent and 43 of European descent) from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study were included.
Methods:
Global and sectoral rim areas were measured using confocal laser scanning ophthalmoscopy. Masked stereophotograph review determined progression of glaucomatous optic disc damage. The rates of absolute rim area loss and percentage rim area loss in healthy and progressing glaucomatous eyes were compared using multivariate, nested, mixed-effects models.
Main outcome measures:
Rate of rim area loss over time.
Results:
The median follow-up time was 5.0 years (interquartile range, 2.0-7.4 years) for healthy eyes and 8.3 years (interquartile range, 7.5-9.9 years) for progressing glaucoma eyes. The mean rate of global rim area loss was significantly faster in progressing glaucomatous eyes compared with healthy eyes for both rim area loss (-10.2×10(-3) vs. -2.8×10(-3) mm(2)/year, respectively; P < 0.001) and percentage rim area loss (-1.1% vs. -0.2%/year, respectively; P < 0.001), but considerable overlap existed between the 2 groups. Sixty-three percent of progressing glaucoma eyes had a rate of change faster than the fifth quantile of healthy eyes. For both healthy and progressing eyes, the pattern of rim area loss and percentage rim area loss were similar, tending to be fastest in the superior temporal and inferior temporal sectors. The rate of change was similar in progressing eyes of patients of African or European descent.
Conclusions:
Compared with healthy eyes, the mean rate of global rim area loss was 3.7 times faster and the mean rate of global percentage rim area loss was 5.4 times faster in progressing glaucoma eyes. A reference database of healthy eyes can be used to help clinicians distinguish age-related rim area loss from rim area loss resulting from glaucoma.
Aims:
To assess the intraobserver agreement, interobserver agreement, and the agreement between a digital stereo optic disc camera (Discam) and Heidelberg retina tomograph (HRT) in measuring area cup-disc ratio (ACDR) and radial cup-disc ratio (RCDR) by two observers.
Methods:
The optic discs of 78 eyes of 39 people (17 cases of primary open angle glaucoma, eight normal tension glaucoma, two ocular hypertension, and 12 normal subjects) were imaged with Discam and HRT. Two observers independently drew the disc margins on the HRT mean topography images and the disc and cup margins on the Discam images. ACDR and the RCDR at various angles were measured with the two systems. Intraobserver agreement, interobserver agreement, and the agreement between the two systems were assessed by 95% tolerance limit of changes (TC) and intraclass correlation coefficient (ICC).
Results:
Eight eyes were excluded due to poor image quality (six Discam and two HRT). 70 eyes were analysed. The intraobserver ACDR agreement was almost perfect in both systems (ICCs = 0.97 and 0.92, and TCs = 11.0% and 15.1% in HRT and Discam respectively). The interobserver ACDR agreement was almost perfect in HRT (ICC = 0.97) and substantial in Discam (ICC = 0.79), (TCs = 10.5% and 24.5% respectively). The ACDR agreement between the two systems was substantial in observer A (ICC = 0.67) and moderate in observer B (ICC = 0.53), (TCs = 24.8% and 46.7% respectively). The HRT measured the ACDR significantly larger than the Discam (p <0.001), and the differences were significantly larger in the glaucomatous group (p <0.001). RCDR agreement between the two systems was fair to substantial in observer A (ICC = 0.36 to 0.74) and slight to moderate in observer B (ICC = 0.12 to 0.45). Both observers achieved the best RCDR agreement between the two systems at the inferior optic disc position.
Conclusion:
There is almost perfect intraobserver agreement in each system. The interobserver agreement was better with the HRT than the Discam. There was substantial variation in ACDR and RCDR agreement between the two systems measured by the two observers. The variation in ACDR and RCDR measurements between the two systems may be too large for interchangeable use in a clinical setting.
4 Die Glaukomerkrankung führt zu typischen strukturellen Änderungen im Sehnervenkopf und der retinalen Nervenfaserschicht (RNFS). Die Erkennung und Beschreibung dieser Befunde und die Messung von Änderungen über die Zeit sind fundamentale Bausteine der Glaukomdiagnose und der Verlaufskontrolle. Die Interpretation der Befunde der klinischen Untersuchung des Sehnervenkopfes und der RNFS ist komplex, weil sich auch normale Sehnervenköpfe in Größe und Form beträchtlich voneinander unterscheiden können, und weil auch andere Krankheiten mit diesen assoziiert sein können. Es gehört unzweifelhaft zu den schwierigsten Aufgaben eines Ophthalmologen, das Erscheinungs-bild des Sehnervenkopfes zu bewerten, um daraus die Stabilität oder die Progression der Erkrankung zu erkennen. In der klinischen Praxis wird die Beurteilung dieser Strukturänderungen gewöhnlich mit Hilfe der Fundus-Biomikroskopie und der Beurteilung von Stereofotografien des Seh-nervenkopfes vorgenommen. Derartige akribische Untersuchungen mit der Spaltlampe sind sicherlich sinnvoll, dennoch fehlen ihnen Objektivität und Quantifizierbarkeit. Fotografien des Sehnervs sind objektive Dokumente, die einen Vergleich von Befunden über die Zeit ermöglichen, die aber einer zusätzlichen subjektiven Interpretation oder einer Falschfarben-Computeranalyse bedürfen. Sie sind sehr anfällig gegen Medien-trübung und die Bedingungen während der Bildaufnahme (Exposition, Lichtquelle, digitale Bildverarbeitung), die das Erscheinungsbild der Retinastrukturen deutlich beeinflussen können. Sowohl Fotografien als auch klinische Untersuchungen gehören zur Standard-Diagnostik bei Glaukom-Patienten. Objektive und quantitative Messungen des Sehnervenkopfes und der RNFS können die Beurteilung einer glaukomatösen Schädigung ergänzen und dabei helfen, die Progression der Krankheit festzustellen. Ziel dieses Beitrags ist es, eine systematische Vorgehensweise für die klinische Interpretation der HRT II Ergebnisse aufzuzeigen und den Nutzen der HRT-Technik zum Zeitpunkt der Erstuntersuchung zu diskutieren.
To investigate the temporal relationship between optic nerve head (ONH) surface depression and retinal nerve fiber layer (RNFL) thinning measured by confocal scanning laser ophthalmoscopy (CSLO) and spectral-domain optical coherence tomography (SD-OCT), respectively, during the course of glaucoma progression.
Because glaucomatous damage is irreversible early detection of structural changes in the optic nerve head and retinal nerve fiber layer is imperative for timely diagnosis of glaucoma and monitoring of its progression. Significant improvements in ocular imaging have been made in recent years. Imaging techniques such as optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy rely on different properties of light to provide objective structural assessment of the optic nerve head, retinal nerve fiber layer and macula. In this review, we discuss the capabilities of these imaging modalities pertinent for diagnosis of glaucoma and detection of progressive glaucomatous damage and provide a review of the current knowledge on the clinical performance of these technologies.
Purpose:
To determine the agreement between Heidelberg Retinal Tomograph (HRT; Heidelberg Instruments, Heidelberg, Germany) and visual field examinations in differentiating normal from glaucomatous eyes and to evaluate the sensitivity and specificity of HRT optic disc examination in detecting eyes with glaucomatous damage.
Study design:
Cross-sectional study.
Participants:
Three hundred fifty-nine patients, for a total of 359 eyes (55 normal, 209 with ocular hypertension [OHT], and 95 with primary open-angle glaucoma).
Intervention:
Optic disc imaging by HRT, using a 10 degrees angle view; a mean of three repeated images were analyzed using version 2.01 software. The optic disc was classified as "normal/glaucomatous" on the basis of multivariate discriminant analysis and cumulative frequency distribution (ranked-segment distribution curves). The visual field was examined using the DS 30 II program (Humphrey perimeter, Zeiss Humphrey System, Dublin, CA), with a glaucomatous visual field being defined on the basis of an abnormal glaucoma hemifield test and a statistically significant corrected pattern standard deviation less than 4 dB.
Main outcome measures:
Agreement between HRT and visual field examinations calculated by means of the kappa statistic and the sensitivity and specificity of HRT examination.
Results:
The agreement between the visual field-based and HRT definition of glaucoma was fair to poor, with a kappa statistic of between 0.48 and 0.28. The sensitivity and specificity of the HRT examination were, respectively, 80% and 65%, according to Mikelberg's analysis, and, respectively, 31% to 53% and 90% to 92%, according to the analysis based on cumulative curves of normality.
Conclusions:
In a broad clinical setting including normal, OHT, and glaucoma patients, the HRT and visual field tests have fair to poor agreement in detecting glaucoma. The HRT demonstrated a lack of specificity when using Mikelberg's multivariate discriminant analysis and a lack of sensitivity when using cumulative frequency distribution (ranked-segment distribution) curves. These values did not change when normal or OHT patients were excluded from the analysis. In the clinical setting, caution should be used when interpreting HRT results on the basis of multivariate discriminant analysis or cumulative frequency distribution curves.
Automated structural measurements of retinal nerve fibers and optic nerve head are possible with new lasers providing objective and reproductible data for analysis. Scanning laser polarimetry (GDx VCC), based on retardation of polarized light, assesses peripapillary nerve fiber layer thickness. Confocal scanning laser tomography yields precise topographic maps of the optic disc and peripapillary retina. The advantages, applications for glaucoma detection, both in a screening setting as well as for monitoring progression, limitations and pitfalls need to be well known and results should be analyzed with clinical data.
Chronic open-angle glaucoma is a progressive optical neuropathy. Automated imaging of the optic disc and optic nerve fibers provides reliable analysis of the optic nerve as well as long-term follow-up of neuropathy patients. HRT, GDX-VCC, and OCT, which analyze the optic disc and optical fibers, provide indisputable assistance in improving screening techniques and the follow-up of progressive glaucoma.
Objective
To evaluate the optic disc for structural abnormalities in the contralateral eye of unilateral normal pressure glaucoma patients.
The posterior pole ganglion cell bodies form a substantial fraction of the retinal thickness, prompting the authors to study the feasibility of detecting, by scanning retinal thickness analysis, retinal changes at the posterior pole due to glaucomatous damage.
Nonconsecutive case series.
One or both eyes of patients with chronic open-angle glaucoma who presented with either a superoinferior asymmetry in visual fields or a localized field loss or a nerve fiber layer defect visible on photography were recruited. Twenty-nine eyes of 18 patients were studied.
A laser slit was projected on the retina and scanned, in 400 msec, across a 2- x 2-mm area of the fundus, yielding optical cross-sections that were digitally recorded. Nine such scans covered the central 20 degrees of the fundus. The optical cross-sections were analyzed by an operator-free algorithm to yield a three-or two-dimensional color map. The asymmetry (difference) between the visual sensitivity of the upper and lower hemifields was compared with the asymmetry in retinal thickness deviation from normal.
Large losses (up to 34%) in retinal thickness were detected at the posterior pole of patients with glaucoma due to the loss of ganglion cells and nerve fibers. A statistically significant correlation was found between the asymmetry in visual sensitivity loss and the asymmetry in deviation from normal thickness (r = 0.72; P < 0.0005).
Mapping of the retinal thickness may provide a sensitive method for the detection and monitoring of early glaucomatous tissue loss in the posterior pole, which is unique due to the combination of (1) the direct measurement of neuroretinal loss in the central field of vision; (2) the mapping capability; and (3) the rapid image acquisition.
The purpose of this study was to study the effect of a subpixel image alignment algorithm on the standard deviation (SD) of mean topography images obtained by laser scanning tomography and to evaluate changes of the cup shape measure parameter (CSM) over time based upon the individual parameter variability using the new algorithm. Triple measurements from optic nerve heads of 132 eyes of 132 subjects were obtained using the Heidelberg Retina Tomograph HRT. To calculate a mean topography image from three single topography images, alignment of the raw optical section image data was performed with the standard software and again with a new subpixel-based image alignment algorithm. The effect on the averaged (SD) of the mean topography images was evaluated. CSM was evaluated in 15 eyes of 15 normal subjects (N) and 28 eyes of 14 glaucoma patients (G) over a period of 28.6 ± 4.6 months (N) and 28.56 ± 5.2 months (G) respectively. A change in the CSM value over time was considered significant if CSM measurements exceeded two standard deviations of this variable determined for the individual eye. Mean-topography image SD was 22.86 ± 8.2 microns (min. 9.5 μm; max. 47.8 μm) with the standard alignment procedure and 15.46 ± 6.8 μm (min. 6.8 μm; max. 42.8 μm) with the new algorithm. The average SD improvement was 7.46 ± 3.9 microns (min. −8.1μm; max. 28.7μm). The coefficient of correlation of both methods was R2 = 0.77 (p < 0.0001). No control group eye demonstrated significant changes of CSM in the follow-up period. The CSM indicated an increase in cup steepness in 4 eyes of 4 glaucoma patients. In one of these four eyes, a deterioration of the visual field was identified by white on white perimetry. The new image alignment algorithm significantly reduces the SD of mean topography images calculated from identical raw data. If topometric variables are evaluated over time, the individual variability of data should be taken into account.
Background: To monitor the efficiency of glaucoma therapy it is necessary to detect progression of the disease as soon as possible. This survey presents the results on functional and morphological approaches to detect glaucoma progression. Material and Methods: Risk factors identified in the therapeutic intervention studies should be used to evaluate the possible risk for progression. The functional test approaches of standard achromatic perimetry (SAP), short wavelength automated perimetry (SWAP) and frequency doubling technology (FDT) are described. Furthermore, morphologic changes are described by means of optic nerve head and nerve fiber photography, optic nerve head tomography, optic coherence tomography and nerve fiber polarimetry. Results: The risk factors identified in the interventional studies were as follows: 1. higher intraocular pressure, 2. worse mean deviation (MD), 3. older age, and 4. frequent disc hemorrhages. Additionally, in patients with normal pressure glaucoma, migraine headaches were identified. Patients with ocular hypertension showed a higher risk of conversion into open angle glaucoma in case of higher pattern standard deviation (PSD), thinner central corneal thickness and larger vertical cup-to-disc ratio. The optic nerve head photography was the standard procedure of morphological monitoring in the interventional studies. A direct comparison of the available techniques on nerve fiber thickness and optic nerve head morphology is not yet available. SAP represents the functional methodology with the most validated results. SWAP and FDT showed that progression in early glaucoma can be detected before SAP damage occurs. Conclusion: Glaucoma patients should be regularly tested with SAP and optic nerve head photography. Automated nerve fiber or optic nerve head morphology measuring techniques might be favourable to complete the diagnostic monitoring. In patients without glaucomatous damage SWAP and FDT may be able to detect changes earlier than SAP. The results of a review of the literature are presented and discussed for each technology.
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.
Purpose:
To detect pathologic changes in retinal nerve fiber bundles in glaucomatous eyes seen on images obtained by adaptive optics (AO) scanning laser ophthalmoscopy (AO SLO).
Design:
Prospective cross-sectional study.
Methods:
Twenty-eight eyes of 28 patients with open-angle glaucoma and 21 normal eyes of 21 volunteer subjects underwent a full ophthalmologic examination, visual field testing using a Humphrey Field Analyzer, fundus photography, red-free SLO imaging, spectral-domain optical coherence tomography, and imaging with an original prototype AO SLO system.
Results:
The AO SLO images showed many hyperreflective bundles suggesting nerve fiber bundles. In glaucomatous eyes, the nerve fiber bundles were narrower than in normal eyes, and the nerve fiber layer thickness was correlated with the nerve fiber bundle widths on AO SLO (P < .001). In the nerve fiber layer defect area on fundus photography, the nerve fiber bundles on AO SLO were narrower compared with those in normal eyes (P < .001). At 60 degrees on the inferior temporal side of the optic disc, the nerve fiber bundle width was significantly lower, even in areas without nerve fiber layer defect, in eyes with glaucomatous eyes compared with normal eyes (P = .026). The mean deviations of each cluster in visual field testing were correlated with the corresponding nerve fiber bundle widths (P = .017).
Conclusions:
AO SLO images showed reduced nerve fiber bundle widths both in clinically normal and abnormal areas of glaucomatous eyes, and these abnormalities were associated with visual field defects, suggesting that AO SLO may be useful for detecting early nerve fiber bundle abnormalities associated with loss of visual function.
Purpose:
To determine through retrospective file analysis which clinical factors best predict glaucomatous optic neuropathy as evaluated by Heidelberg retinal tomography (HRT II) imaging.
Methods:
One HUNDRED twenty-two records from patients referred for HRT imaging at the University of Waterloo Ocular Heath Clinic met inclusion criteria for this study and were reviewed. Topographic change analysis (TCA) data generated by HRT were examined in addition to the following clinical information: diastolic blood pressure, right arm sitting, intraocular pressure, and central corneal thickness. All HRT scans included were required to have 20 μm or better standard deviation (SD) on acquisition and deemed "very good" quality or "excellent" by HRT software. Based on previously defined published HRT TCA change criteria, each patient was allocated to one of the following groups: stable, borderline, or progressive.
Results:
Diastolic perfusion pressure (DPP) was found to be significantly lower in the borderline and progressive groups compared with the stable group (P < 0.001). DPP was also lower significantly lower in the progressive group compared with the borderline group (P < 0.001).
Conclusions:
Low DPP appears to be a reasonable predictor of progressive optic neuropathy as determined using scans of <20 μm SD on the HRT TCA platform. DPP of 56 mm Hg or lower appears to be a clinically useful threshold to identify patients at increased risk of progressive optic neuropathy.
In addition to classical stereo-disc photography, various glaucoma imaging devices were developed in the last two decades to quantitatively measure and record glaucoma-related structural parameters of the eye. In determining whether or not the glaucomatous damage progressed from baseline and in estimating the number of test results' optimal frequency needed to confirm disease progression, information relating to the test-retest variability of measurement results provided by each imaging device is indispensable. Such information enables the clinician to apply these devices in practice. The test-retest variability of a system is usually estimated using the Bland-Altman analysis and by calculating the coefficient of variation (CV), intraclass correlation coefficient (ICC), and minimum detectable changes (MDC). The reported CV, ICC, and MDC values for glaucoma-related structural parameter measurement results of stereo-disc photographs, confocal scanning laser ophthalmoscopes, scanning laser polarimeters, time-domain optical coherence tomography (OCT), spectral-domain OCT (SD-OCT), anterior-segment OCT, and ultrasound biomicroscope are systematically reviewed in this manuscript, which will enable the clinician to interpret measurement results provided by each glaucoma imaging devices and thus be useful in practice. Although SD-OCT systems may be currently prevailing because of the volume of information provided and the relatively better test-retest variability, these systems need improvement in their test-retest variability measurement capabilities.
Background:
This study was carried out to investigate the effect of the cardiac cycle on topographic measurements of the optic nerve head and peripapillary retina with confocal scanning laser tomography.
Methods:
The sample comprised 25 healthy subjects (mean age 40.44 years, range 23-67 years). Using a random crossover design, we obtained a set of three images using the Heidelberg Retina Tomograph (Heidelberg Engineering GmbH, Heidelberg, Germany) under each of two conditions. In the first, the images were obtained normally, while in the second, image acquisition was pulse-synchronised using an electrocardiographic signal. We compared the variability of topographic measurements under the two conditions in the whole image, in the optic nerve head and in the peripapillary retina free of visible vessels.
Results:
Nineteen subjects (76%) showed a decrease in variability in the whole image under the pulse-synchronised condition. The respective numbers for the optic nerve head and peripapillary retina were 20 (80%) and 21 (84%). The decrease in variability ranged widely, with a mean of 13.62% in the whole image, 12.26% in the optic nerve head and 18.51% in the peripapillary retina. These decreases were highly significant. There was no relationship between the decrease in variability and age, intraocular pressure, blood pressure, heart rate or the area of the image occupied by blood vessels.
Conclusion:
Detecting structural change depends on the accurate assessment of each subject's variability. Because the cardiac cycle confounds this assessment by varying and unpredictable amounts, it may be necessary to obtain pulse-synchronised images routinely.
To evaluate the agreement of optic disc measurements obtained with the Cirrus high-density optical coherence tomography (HD-OCT) and the Heidelberg retina tomograph (HRT) and compare the intervisit, test-retest variability between the instruments.
Prospective, cross-sectional study.
Two hundred seven subjects (109 glaucoma and 98 normal subjects).
One eye from each individual was selected randomly for optic disc imaging by the Cirrus HD-OCT and the HRT. Areas of the optic disc and the cup, cup volume, vertical cup-to-disc ratio and cup-to-disc area ratio were compared between the instruments. The OCT measurements were corrected for ocular magnification using the Littman's formula. The measurement agreement was evaluated with the Bland-Altman plots. The intervisit test-retest variability was examined in 17 randomly selected glaucoma patients who underwent optic disc imaging weekly for 8 consecutive weeks. The intraclass correlation coefficients (ICC) and the reproducibility coefficients of the optic disc parameters were computed.
Measurement agreement, reproducibility coefficients, and ICCs of optic disc parameters.
The OCT measured smaller optic disc and rim areas and greater cup volume, vertical cup-to-disc ratio and cup-to-disc area ratio than the HRT did (all with P<0.001). There were proportional biases in the Bland-Altman plots between OCT and HRT optic disc measurements except for rim area and cup-to-disc area ratio. The 95% limits of agreement of rim area ranged between -0.28 and 0.88 mm(2) before, and between -0.22 and 0.92 mm(2) after correction for ocular magnification. Both OCT and HRT showed high test-retest reproducibility with ICCs ≥ 0.921. Although the reproducibility coefficient of OCT rim area (0.093 mm(2); 95% confidence interval [CI], 0.081-0.105 mm(2)) was significantly smaller than that of the HRT (0.186 mm(2); 95% CI, 0.163-0.210 mm(2); P = .018), there were no differences in the ICCs between the instruments.
Optic disc assessment by spectral-domain OCT and confocal scanning laser ophthalmoscopy demonstrates poor agreement but similarly low test-retest variability. The source of their disagreement and its effects on the detection of progression require further study.
The 1990s have ushered in a wave of new technologies for the diagnosis and management of the glaucoma patient. These advances bring to the clinician a new level of assessment and reproducibility of clinical evaluations to assist in the therapy. Among the many changes in this arena are scanning laser ophthalmoscopy for the assessment of optic nerve head topography and nerve fiber layer analysis, the development of short wavelength automated perimetry (SWAP), SITA (Swedish Interactive Threshold Algorithm) and the introduction of frequency doubling technology.
Scanning laser tomography using the Heidelberg Retina Tomograph (HRT) aims at a three-dimensional reconstruction of optic disk topography based on two-dimensional optical section images. Topometric parameters describe the optic disk configuration, algorithms calculate the likelihood of already existing glaucomatous tissue alterations. In the follow-up of chronic glaucoma, this imaging technique has become the gold standard for quantitative optic nerve head evaluation.
© Georg Thieme Verlag KG Stuttgart · New York.
Although event analysis (EA) and trend analysis (TA) have been widely adopted to evaluate glaucoma progression in clinical trials, there is poor agreement between the strategies and no consensus on strategy selection in clinical practice. With computer simulation of progressive loss of the retinal nerve fiber layer (RNFL), the authors compared the performance of TA and EA for the detection of glaucoma progression.
RNFL progression was modeled with reference to the individual's test-retest variability and the pattern and rate of progression. The sensitivity and specificity of each scenario were computed from 5000 simulated datasets. Simulation results were validated with longitudinal RNFL measurements obtained from 107 glaucoma and glaucoma suspect patients who had a median follow-up period of 38 months.
TA generally attained a sensitivity ≥80% earlier than EA, although EA with a group reproducibility coefficient had a higher sensitivity than TA for eyes with a large test-retest variability in the early follow-up period, albeit at a lower specificity. The specificity of TA was 95% and ranged between 80% and 100% for EA. Independent of test-retest variability and the pattern and rate of progression, TA had an accuracy ≥80% earlier than EA. In the longitudinal study, the detection rate was 42%, 35%, and 3% for TA, whereas it was 11% to 40%, 12% to 28%, and 3% to 23% for EA at 36 months of follow-up in eyes with small, average, and large test-retest variabilities, respectively.
Although test-retest variability is an important determinant in progression analysis, TA generally outperformed EA for the detection of RNFL progression in glaucoma.
Glaucoma is an optic neuropathy in which optic nerve changes are important in diagnosis and progression, because the visual field may remain normal even while the optic nerve is undergoing significant damage. Accurate methods to objectively document the appearance of the optic nerve are necessary. In order for an optic disc imaging system to be clinically useful for detecting change, its reproducibility must be established.
We measured the reproducibility of duplicate measurements in 59 eyes of 31 consecutive patients, grouped into glaucoma subjects (n = 29) and eyes with glaucoma (n = 30), with the 3.10 OIS Glaucoma-Scope. In order to simulate two visits on one day, sets of three optic disc images were obtained first, followed by a repeat set, and the best disc images of each (chosen by the computer) were compared.
The coefficients of variation of duplicate measurements for glaucoma suspects and patients with glaucoma were respectively: vertical cup/disc (c/d) ratio, 6.3% and 3.47%; horizontal c/d ratio, 4.61% and 2.97%; c/d area, 3.29% and 1.37%; cup area, 1.82% and 1.72%; mean position (MP) disc, 13.3% and 10.42%; MP total, 10.1% and 13.2%. For three eyes the examination was not possible (opacification of posterior capsule, miosis).
These results suggest that the 3.10 version of the OIS Glaucoma-Scope allows reproducible measurements in living eyes.
Many pathological conditions of the eye and of the body as a whole cause changes in the color and three-dimensional shape of the ocular fundus. Glaucoma is probably the best known of these conditions. (For some examples, see [1] through [9].) It causes increases in the pallor and cupping of the optic nerve head. Therefore, it would obviously be of great potential value for research on and diagnosis and treatment of these diseases if the shape and color of the fundus could be measured with precision, and several different procedures have been developed at various laboratories around the world to try to do that ([10] through [34]).
We describe the application of confocal laser scanning microscopy for three-dimensional measurements of the eye in vivo. Formation and analysis of three-dimensional images are discussed using the example of the optic nerve head. The accuracy of height measurements at this structure is better than 50 microns and can be improved significantly by using active optical components.
We determined the magnitude of variability in optic disc topographical parameters on digital analysis of the optic disc using the IS 2000. The variability introduced by the system, the observer, the observer and patient, and by clinically different types of discs was assessed in the measurement of the vertical cup-to-disc ratio, horizontal cup-to-disc ratio, cup area-to-disc area, cup volume, neuroretinal rim area, and neuroretinal rim area-to-disc area. The system itself accounted for no variability. The variability introduced by one observer for the parameters ranged from 1% to 7%, and by one observer and patient from 1% to 28%. The variation among five observers ranged from 1% to 55%. Direct image acquisition (using video cameras) gave results that were no different from those obtained by digitizing the slides. Contrast-enhancement techniques did not decrease observer variability. A change in the flash intensity level at which optic disc images were acquired from 94.5 to 15.0 Watt-seconds introduced a variability of 3% to 21%. These results are less variable than those obtained on clinical observation and comparable to those of the Rodenstock image analyzer in evaluating these aspects of optic disc topography.
A confocal scanning diode laser ophthalmoscope (Retina Tomograph, Heidelberg Engineering, GmbH, Heidelberg, F.R.G.) was used to examine the optic nerve head in both normal healthy (n = 10) and glaucomatous (n = 10) eyes. An image series was obtained from 32 transverse optical sections taken at consecutive height planes (50-80 mum each) over a 1.5-2.5-mm scan depth. Each image was then analyzed to create a topographic map containing 256 +/- 256 pixels (65,536 pixels) with afield of view of 10+/-. Images were obtained through undilated pupils. Reproducibility was 30.1 +/- 7.0 and 31.8 +/- 10.6 mum in normal and glaucomatous eyes, respectively. The instrument provides highly reproducible topographic data of the optic nerve head in patients with undilated pupils.
The Heidelberg retina tomograph is a confocal scanning laser ophthalmoscope that permits recording of topographic information related to the optic nerve and retina. We studied the reproducibility of the topographic parameters obtained by recording five times sequentially the images obtained from one eye of five healthy people and five glaucoma patients. The reproducibility coefficients ranged from 60.5 to 99.4%. The results indicate that, for the parameters examined, the instrument has a high level of reproducibility.
We studied the variability of optic disk and peripapillary nerve fiber layer surface contour measurements made by use of computer-image analysis. Six hundred twenty-five measurements of surface contour were made on each eye by use of simultaneous stereoscopic videography. Regional differences in short-term measurement variability were studied in 12 eyes (six normal and six glaucomatous), each imaged nine times over several days. The widths of the 95% confidence interval for the measurements averaged 82 microns for the juxta-papillary surface and 132 microns for the disk surface. Measurements of peripapillary surface contour were significantly less variable than were measurements of the disk surface (P = .000). The greatest variability was detected along large blood vessels and at steep contours. Long-term variability was studied in a separate group of 30 clinically stable patients with glaucoma, each imaged three to six times over a period of more than one year. The widths of the 95% confidence intervals were 132 microns for the peripapillary surface and 217 microns for the disk surface. The long-term variability was significantly greater than the short-term variability (P = .000). The peripapillary nerve fiber layer surface, located away from the margins of large vessels, may provide the most dependable measurements of contour. These estimates of long-term variability of optic disk and peripapillary contour measurements provide clinically relevant confidence intervals with which to detect progressive glaucomatous nerve fiber damage.
We acquired five independent topographic images of the optic nerve head of eight normal eyes and eight eyes with primary open-angle glaucoma with a laser tomographic scanner. Each image had a field of view of 15 x 15 degrees with a resolution of 256 x 256 pixels. The pixel size was approximately 15 x 15 microns. The value of a pixel of a topographic image represented the height at this position. The mean height and the standard deviation over the five topographic images were calculated for each of the 65,536 pixel positions. The standard deviation of a single height measurement in normal eyes was 38.7 microns (range, 23.4 to 62.2 microns) for areas in the peripapillary retina and 42.6 microns (range, 24.4 to 53.7 microns) for measurements within the optic nerve head area. In glaucomatous eyes, the standard deviation was 41.2 microns (range, 23.2 to 59.6 microns) in the peripapillary retina and 49.4 microns (range, 28.1 to 72.8 microns) within the optic nerve head. There was no significant difference between the standard deviation of a single height measurement in normal and glaucomatous eyes (P = .34 within the optic nerve head area; P = .57 on peripapillary retina). No correlation was found between standard deviation of the measurements and pupil size or age of the subject.
To study the retinal surface in the human eye in normal and diseased states we used laser scanning tomography. The confocal arrangement of the laser tomographic scanner permits examination of retinal topography in the axis perpendicular to the retinal surface. The eyes examined with the laser tomographic scanner included normal eyes, eyes with macular holes, impending macular holes, radiation retinopathy, macular edema, photocoagulation scars, subfoveal scars, and serous detachment of the fovea associated with subretinal neovascularization. The laser tomographic scanner is a new method that allows measurements of the topography of the internal limiting membrane in the macular area and may improve our understanding of the pathophysiologic characteristics and treatment of a variety of disorders of the macula.
Computerized topographic mapping of 10 repeated fundus images of one eye each in 10 healthy subjects and in 10 subjects with elevated intraocular pressures (IOPs) was performed with the Humphrey Retinal Analyzer. The variability of depth measurements at 400 to 650 individual locations in the optic nerve head and peripapillary retina was evaluated. The average size of the 95% confidence intervals for individual depth measurements for healthy subjects and those with elevated IOPs were 166 and 232 microns in the optic nerve head and 205 and 261 microns in the peripapillary retina, respectively. Variability was significantly less for healthy subjects than for those with elevated IOPs. Variability was significantly greater for depth measurements in the peripapillary retina than for measurements in the optic head. Knowledge about variability of individual depth measurements is useful for proper interpretation of computerized topographic mapping to detect retinal nerve fiber damage.
Topographic analysis and measurement of the optic nerve head is important for the diagnosis and follow-up of glaucoma. To quantify structures of the optic nerve head the new technique of laser tomographic scanning was used. A laser beam was focused onto the surface of the optic nerve head and the reflected light was detected in a confocal detection unit. The consequent change of focus produced a tomographic scanning series and allowed measurement of three-dimensional structures. To analyze the reproducibility of optic cup measurements the authors did ten recordings of one eye of eight normal volunteers. The mean standard deviation of the measurements was +/- 0.015 mm3 and the mean coefficient of variation was 9.5%. Confocal laser tomographic scanning is a safe, effective, convenient method to measure and document the topography of the optic nerve head and should be a valuable technique for follow-up of glaucoma patients.
Computerized digital image analysis of the optic nerve head was performed using a simultaneous stereoscopic video camera system to provide rapid, quantitative measurements of optic nerve head topography. Determination of the variability of the measurements is required to estimate the magnitude of optic nerve change over time that can be reliably detected. Total variability, operator variability, and interoperator variability were studied. Total variability was assessed by analyzing ten sets of video recordings made in each of seven eyes of seven normal subjects, and in seven eyes of seven patients with glaucoma. The median coefficients of variation for measurements of total variability in glaucoma patients were as follows: vertical disc measurement, 1.4%; horizontal disc measurement, 2.1%; disc area, 1.9%; vertical cup/disc, 3.9%; horizontal cup/disc, 3.3%; disc rim area, 7.5%; and volume, 7.6%. Operator and interoperator variabilities were considerably smaller in magnitude.
The video-ophthalmograph records the topography of the optic disk via simultaneous stereoscopic images which are stored and analyzed with the help of a microcomputer. This information is used to generate the vertical cup-disk ratio, the vertical optic disk diameter, the cup volume, and the neuroretinal rim area. To determine the reliability of the data, we recorded information for one eye of each of five patients ten times to determine the interphotographic error variance. We also analyzed one photograph for each of five patients ten times to determine the intraphotographic variance attributable to repeated analysis of the same photograph. The interphotographic and intraphotographic coefficients of variation were 2% to 18% and 2% to 7% respectively for these measurements.
The reproducibility of optic disc cup measurements was analyzed in 24 eyes of 24 patients [8 normals, 8 glaucoma patients, 8 glaucoma suspects] using the Laser Tomographic Scanner. The mean coefficient of variation in triple measurements was 5.0% for the cup area, 5.4% for the rim area, 7.0% for the cup volume, 4.0% for the mean cup depth, and 4.3% for the maximum cup depth. Mean reliability between two of the three measurements performed in each eye was better than 0.988 for the cup area, 0.995 for the cup volume and 0.996 for the mean cup depth readings. These results suggest that laser scanning tomography allows highly reproducible measurements in living eyes and adds an important tool to the ophthalmologist's armamentarium for the diagnosis and follow-up of glaucoma patients.
Glaucoma is an optic neuropathy in which changes in the appearance of both the optic nerve head and the surrounding tissues are important in both diagnosing its presence and progression. Accurate methods to objectively document the appearance of the optic nerve are necessary. The confocal laser scanning ophthalmoscope (Zeiss) is a new prototype instrument that may have the capability to accurately perform this function.
The authors performed a prospective pilot study evaluating the ability of the confocal laser scanning ophthalmoscope to reproduce three-dimensional optic nerve images. Each retinal image contained 600,000 bytes of information. Thirty discrete images of the right optic nerves of 19 visually normal volunteers were obtained. Depth measurements were compared from the same 100 x 100 micron areas (neighborhoods).
Image comparisons found the variability of depth measurements for the entire image were within 102 microns (95% confidence interval). Sixty percent of the depth measurements were reproducible within 100 microns. Variability of the depth measurements was greatest where the neuroretinal rim sloped at the edge of the optic cup and lowest in the peripapillary area.
The confocal laser scanning ophthalmoscope has the potential to be a safe, rapid, and reproducible method of imaging ocular structures.
A confocal scanning diode laser ophthalmoscope was used to determine the number of examinations needed to obtain highly reproducible topographic measurements of the optic nerve head and peripapillary retina.
Topographic images of the optic nerve head and peripapillary retina were obtained in one randomly selected eye on five separate visits. On each occasion the selected eye had five examinations. For each examination, one image was acquired (a total of 25 images per eye). Reproducibility was calculated as the average SD of all image elements (65,536 pixels).
Glaucoma referral center.
Five normal subjects and five patients with glaucoma.
Topographic imaging of the optic nerve head and peripapillary retina.
Number of examinations needed to obtain highly reproducible topographic measurements.
In healthy subjects, reproducibility with one examination per visit was 35.5 microns; this improved to 25.7 microns with three examinations and 22.5 microns with five examinations. In older patients with glaucoma, the reproducibility improved from 40.2 microns with one examination per visit to 28.5 and 24.1 microns with three and five examinations, respectively.
We recommend a series of three examinations to provide high reproducibility with optimal efficiency in terms of time and materials used.
Reproducibility of topometric data acquisition in normal and glaucomatous optic nerve heads with the laser tomographic scanner.
- Rohrschneider K.
- Burk R.O.W.
- Völker H.E.