Heidelberg Retina Tomograph und Papille Medline Abstracts November 1996 bis August 2001

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1 Heidelberg Retina Tomograph und Papille Medline Abstracts November 1996 bis August 2001 Invest Ophthalmol Vis Sci 2001 Aug;42(9): Detecting early glaucoma by assessment of retinal nerve fiber layer thickness and visual function. Bowd C, Zangwill LM, Berry CC, Blumenthal EZ, Vasile C, Sanchez-Galeana C, Bosworth CF, Sample PA, Weinreb RN. Glaucoma Center, Department of Ophthalmology, University of California San Diego, La Jolla , USA. PURPOSE: To compare the abilities of scanning laser polarimetry (SLP), optical coherence tomography (OCT), short-wavelength automated perimetry (SWAP), and frequency-doubling technology (FDT) perimetry to discriminate between healthy eyes and those with early glaucoma, classified based on standard automated perimetry (SAP) and optic disc appearance. To determine the agreement among instruments for classifying eyes as glaucomatous. METHODS: One eye of each of 94 subjects was included. Healthy eyes (n = 38) had both normal-appearing optic discs and normal SAP results. Glaucoma by SAP (n = 42) required a repeatable abnormal result (glaucoma hemifield test [GHT] or corrected pattern standard deviation [CPSD] outside normal limits). Glaucoma by disc appearance (n = 51) was based on masked stereoscopic photograph evaluation. Receiver operating characteristic (ROC) curve areas, sensitivities, and specificities were calculated for each instrument separately for each diagnosis. RESULTS: The largest area under the ROC curve was found for OCT inferior quadrant thickness (0.91 for diagnosis based on SAP, 0.89 for diagnosis based on disc appearance), followed by the FDT number of total deviation plot points of < or =5% (0.88 and 0.87, respectively), SLP linear discriminant function (0.79 and 0.81, respectively), and SWAP PSD (0.78 and 0.76, respectively). For diagnosis based on SAP, the ROC curve area was significantly larger for OCT than for SLP and SWAP. For diagnosis based on disc appearance, the ROC curve area was significantly larger for OCT than for SWAP. For both diagnostic criteria, at specificities of > or =90% and > or =70%, the most sensitive OCT parameter was more sensitive than the most sensitive SWAP and SLP parameters. For diagnosis based on SAP, the most sensitive FDT parameter was more sensitive than the most sensitive SLP parameter at specificities of > or =90% and > or =70% and was more sensitive than the most sensitive SWAP parameter at specificity of > or =70%. For diagnosis based on disc appearance at specificity of > or =90%, the most sensitive FDT parameter was more sensitive than the most sensitive SWAP and SLP parameters. At specificity > or = 90%, agreement among instruments for classifying eyes as glaucomatous was poor. CONCLUSIONS: In general, areas under the ROC curve were largest (although not always significantly so) for OCT parameters, followed by FDT, SLP, and SWAP, regardless of the definition of glaucoma used. The most sensitive OCT and FDT parameters tended to be more sensitive than the most sensitive SWAP and SLP parameters at the specificities investigated, regardless of diagnostic criteria. Arch Ophthalmol Jul;119(7): Discriminating between normal and glaucomatous eyes using the Heidelberg Retina Tomograph, GDx Nerve Fiber Analyzer, and Optical Coherence Tomograph. Zangwill LM, Bowd C, Berry CC, Williams J, Blumenthal EZ, Sanchez-Galeana CA, Vasile C, Weinreb RN. Glaucoma Center, Department of Ophthalmology, University of California-San Diego, La Jolla, CA , USA. 1

2 OBJECTIVE: To compare the ability of 3 instruments, the Heidelberg Retina Tomograph (HRT), the GDx Nerve Fiber Analyzer (GDx), and the Optical Coherence Tomograph (OCT), to discriminate between healthy eyes and eyes with early to moderate glaucomatous visual field loss. SUBJECTS AND METHODS: Forty-one patients with early to moderate glaucomatous visual field loss and 50 healthy subjects were included in the study. The HRT, GDx, and OCT imaging and visual field testing were completed on 1 eye from each subject within a 6-month interval. Statistical differences in sensitivity at fixed specificities of 85%, 90%, and 95% were evaluated. In addition, areas under the receiver operating characteristic (ROC) curve were compared. RESULTS: No significant differences were found between the area under the ROC curve and the best parameter from each instrument: OCT thickness at the 5-o'clock inferior temporal position (mean +/- SE, /- 0.04), HRT mean height contour in the nasal inferior region (mean +/- SE, /- 0.04), and GDx linear discriminant function (mean +/- SE, /- 0.04). Twelve HRT, 2 GDx, and 9 OCT parameters had an area under the ROC curve of at least At a fixed specificity of 90%, significant differences were found between the sensitivity of OCT thickness at the 5-o'clock inferior temporal position (71%) and parameters with sensitivities less than 52%. Qualitative assessment of stereophotographs resulted in a sensitivity of 80%. CONCLUSION: Although the area under the ROC curves was similar among the best parameters from each instrument, qualitative assessment of stereophotographs and measurements from the OCT and HRT generally had higher sensitivities than measurements from the GDx. Am J Ophthalmol 2001 Jul;132(1):57-62 Interobserver variability of optic disk variables measured by confocal scanning laser tomography. Iester M, Mikelberg FS, Courtright P, Burk RO, Caprioli J, Jonas JB, Weinreb RN, Zangwill L. Department of Ophthalmology, University of British Columbia, Vancouver, Canada. PURPOSE: To assess the interobserver variation of confocal laser scanning tomographic measurements of the optic nerve head and to address the question of whether the addition of clinical optic disk photographs is helpful in outlining the optic disk margin and in reducing the observerrelated variation of the measurements. PATIENTS AND METHODS: Optic disk variables for 16 eyes of 16 patients with glaucoma, generated by confocal laser scanning laser tomography (Heidelberg Retina Tomograph), were independently evaluated by four experienced glaucoma specialists, and the interobserver variability was calculated. A second separate review by the same observers included the use of clinical stereoscopic color optic nerve head photographs to aid definition of the optic disk margin. RESULTS: Optic disk parameters with the smallest interobserver variation were cup shape measure, maximum cup depth, height variation contour, and mean height contour. The intraobserver variation of these parameters did not increase when clinical optic disk slides were additionally available. Parameters with the highest interobserver variation were volume below surface, volume below reference, volume above surface, and volume above reference. The observer variation of these optic disk parameters increased significantly for two of the four examiners when clinical optic disk slides were additionally available for outlining the optic disk margin. CONCLUSION: Confocal laser scanning tomography of the optic nerve head can be improved significantly if clinical optic disk photographs are additionally available to help in outlining the optic disk margin. Because interobserver variation in the tomographic optic disk measurements can be significant, even if experienced observer are involved, tomographic optic disk measurements may be centralized in reading centers in the case of multicenter studies. Am J Ophthalmol 2001 Jun;131(6): The effects of astigmatism and working distance on optic nerve head images using a Heidelberg Retina Tomograph scanning laser ophthalmoscope. 2

3 Sheen NJ, Aldridge C, Drasdo N, North RV, Morgan JE. Department of Optometry and Vision Sciences, Cardiff University, Cardiff, United Kingdom. PURPOSE: To determine effects of astigmatism and working distance on optic nerve head images in normal patients using the Heidelberg Retina Tomograph. METHODS: The optic disks of 51 normal healthy subjects, aged 19 to 44 years, were imaged through dilated pupils. Subjects with 0.75 DC or less of astigmatism were imaged without correction at a working distance of 15 mm. They were then re-imaged with a cylindrical correction of DC at 90 degrees axis (n = 20). Naturally astigmatic subjects with more than 1.00 DC were imaged without correction and then reimaged once this was neutralized with their appropriate spectacle prescription (n = 15). The effects of working distance were studied using subjects with 0.75 DC or less (n = 16). Two working distances were used, 15 and 25 mm. At each session the means of three topographic images were taken from which standard deviations and parameters were recorded. Parameters analyzed included cup shape measure, rim area, and inferior temporal rim volume. Z-profile full width at half maximum was calculated from one image per subject for each condition. RESULTS: No significant difference was found in the measured parameters of the optic disk for any astigmatic condition or changes in working distance (P >.05), (paired t test). Both the standard deviation of the mean topographic images and the Z-profile half-maximum width of the axial intensity profile were significantly greater with induced astigmatism of DC (P values 0.3 and.00, respectively). CONCLUSIONS: Optic disk parameters are not significantly affected by uncorrected astigmatism (up to 2.50 DC) or working distance. The algorithm used by the Heidelberg Retina Tomograph to generate topographic maps is sufficiently robust that astigmatism up to 2.50 DC does not require correction. Optom Vis Sci 2001 Jun;78(6): Age-related topographical changes in the normal human optic nerve head measured by scanning laser tomography. Kergoat H, Kergoat MJ, Justino L, Lovasik JV. School of Optometry, University of Montreal, Quebec, Canada. helene.kergoat@umontreal.ca PURPOSE: This study was designed to investigate the effects of advanced aging on the optic nerve head (ONH) structure and retinal nerve fiber layer (RNFL) thickness in the eldest segment of our population. METHODS: Twenty-seven healthy elderly subjects between 75 and 88 years of age (average, / years) and 30 healthy younger subjects between 20 and 32 years of age (average, / years) were recruited for a cross-sectional comparison between ONH morphology and RNFL thickness as measured by scanning laser tomography. The ONH disc, cup, and rim areas; cup-to-disc ratio; and the mean thickness of the RNFL were quantified. RESULTS: The cup and disc areas as well as the cup-to-disc area ratio increased with age, whereas the RNFL thickness decreased during the course of normal senescence. CONCLUSIONS: Any diagnoses of ocular pathology in the elderly must differentiate the effects of normal aging on the ONH topography and RNFL thickness. To that effect, the present study provides a clinical profile of ocular structures that extend into the oldest geriatric age group. Ophthalmic Physiol Opt 2001 May;21(3): The influence of contour line size and location on the reproducibility of topographic measurement with the Heidelberg Retina Tomograph. Roff EJ, Hosking SL, Barnes DA. Neurosciences Research Institute, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK. 3

4 BACKGROUND: The recommended contour line (CL) location with the Heidelberg Retina Tomograph (HRT) is on the inner edge of Elschnig's scleral ring. This study investigated HRT parameter reproducibility when: (i) the CL size is altered relative to Elschnig's ring; (ii) the CL is either redrawn or imported between images. METHODS: Using the HRT, seven 10 degrees images were acquired for 10 normal volunteers and 10 primary open angle glaucoma (POAG) subjects. A CL was drawn on one image for each subject using Elschnig's scleral ring for reference and imported into subsequent images. The CL diameter was then (a) increased by 50 microns; (b) increased by 100 microns; and (c) decreased by 50 microns. To investigate the effect of the method of contour line transfer between images a CL was: (1) defined for one image and imported to 6 subsequent images; (2) drawn separately for each image. RESULTS: Parameter variability improved as the size of the CL increased for the normal group relative to Elschnig's ring but was unchanged in the POAG group. The export/import function (method 1) resulted in better parameter reproducibility than the redrawing method for both groups. CONCLUSIONS: The exporting and importing function resulted in better parameter variability for both subject groups and should be used for transferring CLs across images for the same subject. Increasing the overall CL size relative to Elschnig's scleral ring improved the reproducibility of the measured parameters in the normal group. No significant difference in parameter variability was observed for the POAG group. This suggests that the reproducibility of HRT images are affected more by the variation in topography between images than change in CL definition. Surv Ophthalmol 2001 May;45e:S297-S303 Clinical detection of optic nerve damage: measuring changes in cup steepness with use of a new image alignment algorithm. Burk RO, Rendon R. Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany.burk,reinhard@skbielefeld.de 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 /- 4.6 months (N) and /- 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 /- 8.2 microns (min. 9.5 microm; max microm) with the standard alignment procedure and /- 6.8 microm (min. 6.8 microm; max microm) with the new algorithm. The average SD improvement was /- 3.9 microns (min microm; max microm). The coefficient of correlation of both methods was R(2) = 0.77 (p < ). 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. 4

5 Curr Opin Ophthalmol 2001 Apr;12(2): The diagnostic value of optic nerve imaging in early glaucoma. Mardin CY, Junemann AG. Department of Ophthalmology, Friedrich-Alexander Universitat Erlangen-Nurnberg, Erlangen, Germany. In the last decade, new imaging techniques have been added to conventional fundus photography and have been evaluated for use in early glaucoma. They all measure the loss of neuroretinal rim or retinal nerve fiber layer as a correlate to glaucomatous ganglion cell and axon loss. The value of optic disc photography, planimetry, laser scanning tomography, laser scanning polarimetry, and optical coherence tomography for the diagnosis of glaucomatous eyes in a preperimetric or early perimetric stage is analyzed on the basis of sensitivity, specificity, and receiver operating characteristics (ROC) curves. It becomes clear that all these techniques allow a more or less semiautomated evaluation of the optic disc and retinal nerve fiber layer but still have their limitations in the diagnosis of a very early, preperimetric stage of the glaucoma disease. J Glaucoma 2001 Apr;10(2): Ability of peripapillary atrophy parameters to differentiate normal-tension glaucoma from glaucomalike disk. Park KH, Park SJ, Lee YJ, Kim JY, Caprioli J. Department of Ophthalmology, Seoul National University College of Medicine, Korea. PURPOSE: To investigate the ability of peripapillary atrophy (PPA) parameters to differentiate normal-tension glaucoma (NTG) from glaucomalike disk (GLD). METHODS: Thirty-three eyes of 33 patients with GLD that had no evidence of visual field defect and retinal nerve fiber layer defect and 33 eyes of 33 patients with NTG, matched with age and intraocular pressure, were enrolled. The participants were selected from the database of patients referred from a routine health checkup because of high cup-to-disk ratio (>0.5). Topographic measurements for the optic disk were performed using the Heidelberg Retina Tomograph (HRT). The extent of PPA (zone beta) was measured with Atrophy Zone Analysis software of HRT. Receiver operating characteristic (ROC) curves (GraphROC version 2.0) were used to compare the new formula including PPA parameters with that of the HRT discriminant analysis formula in differentiating NTG from GLD. RESULTS: The area of zone beta, atrophy-to-disk area ratio, and angular and radial extent of zone beta were significantly larger in NTG (P < 0.01). Multiple logistic regression analysis showed that rim area and corrected radial extent of zone beta are variables that show significant difference between NTG and GLD (P < 0.05). The area under the ROC curve for the new formula including rim area and corrected radial extent of zone beta (0.8655) was significantly larger than that for the HRT discriminant analysis formula (0.7351) (P = ). CONCLUSION: The PPA measurement obtained by HRT can be a useful additional tool to differentiate NTG from GLD after the first screening by disk photograph in a routine health checkup. Ophthalmic Physiol Opt 2001 Mar;21(2): How large is the optic disc? Systematic errors in fundus cameras and topographers. Meyer T, Howland HC. Department of Neurobiology and Behavior, W-201 Mudd Hall, Cornell University, Ithaca, NY 14853, USA. PURPOSE: To determine whether or not there are systematic differences in the areas of optic discs as measured by different machines using different measurement algorithms and whether racial or gender differences exist in optic disc area measurements. METHODS: We examined the results of 5

6 twenty-three published studies on the size of normal optic discs of various patient populations. Studies differed in the type of instrument and method used to measure optic disc area, and the number, age, race and gender of subjects examined. Noticing that different machines exhibited statistically significant systematic differences in optic disc sizes of comparable populations, we computed a "normalization" factor for each machine based on these mean differences. Applying this normalization factor to the results, we then re-examined the differences between racial and gender groups. RESULTS: By comparing the results of mean optic disc areas of different racial groups made with different machines, and normalizing results according to those of the Zeiss fundus camera, we found the normalization factors for the following machines to be, Zeiss fundus camera: 1 (by definition), Rodenstock Optic Disc Analyzer (RODA): 1.51, Topcon fundus camera: 1.04, Heidelberg Retina Tomograph (HRT): 1.15 and TopSS scanning laser ophthalmoscope: That is, to bring the results of area measurements made with a RODA machine in line with those made with a Zeiss fundus camera, one should multiply the former by the factor Using the normalized results, we confirmed the findings of previous authors that the optic disc areas of black subjects were statistically significantly larger than those of white subjects (n-weighted mean effect = / S.E., n = 5). Further, the meta-analysis of various racial populations from five studies shows that males have significantly larger discs than females (n-weighted mean effect = /-.055 S.E., n = 9). CONCLUSION: Different machines and techniques give different results when populations of similar racial composition are measured. We recommend applying the above normalizing factors when comparing studies that employ different instruments. Br J Ophthalmol 2001 Mar;85(3): Scanning laser ophthalmoscopy of the optic nerve head in exfoliation glaucoma and ocular hypertension with exfoliation syndrome. Harju M, Vesti E. Helsinki University Eye Hospital, PO Box 220, FIN HYKS, Finland. mika.harju@hueh.fi AIMS: To study the relation between optic nerve head topography (Heidelberg retina tomograph, HRT) and disc area, visual field index mean defect (MD), and intraocular pressure (IOP), and to see whether change in HRT parameters is associated with change in MD in a prospective follow up. METHODS: 80 consecutive patients (69 patients with exfoliation glaucoma and 11 with ocular hypertension combined with exfoliation syndrome) were examined before IOP reducing intervention and prospectively followed every 6 months for 2 years. RESULTS: At the entry point, multiple regression analysis showed significant linear association between MD and all HRT parameters, when controlling for disc area. Disc area showed significant association with cup area, cup/disc area ratio, rim area, cup volume, and mean RNFL thickness. Six months after intervention IOP had decreased significantly. Reversible changes in cup area, cup/disc area ratio, rim area, cup volume, rim volume, mean cup depth, and maximum cup depth were associated with decrease in IOP. During the follow up period from 6 month to 2 years, IOP did not change significantly, and MD was used as a measure of progression of glaucoma. During this period, only cup shape measure among HRT parameters showed significant association with subsequent change in MD. CONCLUSION: Disc area should be taken into account when using HRT to compare patients. Any effect of change in IOP should be also taken into account when using HRT in follow up. Cup shape measure is a promising indicator of progression of glaucomatous damage. Br J Ophthalmol 2001 Mar;85(3): Scanning laser ophthalmoscopy of the optic nerve head in exfoliation glaucoma and ocular hypertension with exfoliation syndrome. Harju M, Vesti E. Helsinki University Eye Hospital, PO Box 220, FIN HYKS, Finland. mika.harju@hueh.fi 6

7 AIMS: To study the relation between optic nerve head topography (Heidelberg retina tomograph, HRT) and disc area, visual field index mean defect (MD), and intraocular pressure (IOP), and to see whether change in HRT parameters is associated with change in MD in a prospective follow up. METHODS: 80 consecutive patients (69 patients with exfoliation glaucoma and 11 with ocular hypertension combined with exfoliation syndrome) were examined before IOP reducing intervention and prospectively followed every 6 months for 2 years. RESULTS: At the entry point, multiple regression analysis showed significant linear association between MD and all HRT parameters, when controlling for disc area. Disc area showed significant association with cup area, cup/disc area ratio, rim area, cup volume, and mean RNFL thickness. Six months after intervention IOP had decreased significantly. Reversible changes in cup area, cup/disc area ratio, rim area, cup volume, rim volume, mean cup depth, and maximum cup depth were associated with decrease in IOP. During the follow up period from 6 month to 2 years, IOP did not change significantly, and MD was used as a measure of progression of glaucoma. During this period, only cup shape measure among HRT parameters showed significant association with subsequent change in MD. CONCLUSION: Disc area should be taken into account when using HRT to compare patients. Any effect of change in IOP should be also taken into account when using HRT in follow up. Cup shape measure is a promising indicator of progression of glaucomatous damage. Am J Ophthalmol 2001 Feb;131(2): Retinal nerve fiber layer evaluation in human immunodeficiency virus-positive patients. Plummer DJ, Bartsch DU, Azen SP, Max S, Sadun AA, Freeman WR. Shiley Eye Center, Department of Ophthalmology, School of Medicine, University of California- San Diego, La Jolla, CA , USA. dplummer@ucsd.edu PURPOSE: To determine the effect of human immunodeficiency virus (HIV) infection on topographic measures of the optic disk and the retinal nerve fiber layer. METHODS: A crosssectional study at the Acquired Immunodeficiency Syndrome (AIDS) Ocular Research Unit at the University of California, San Diego. Retinal nerve fiber layer thickness at the optic nerve head was evaluated using the Heidelberg Retinal Tomograph, a confocal scanning laser tomograph in 38 HIV-positive and 24 age-matched HIV-negative subjects. RESULTS: HIV-positive patients without CMV retinitis showed significant differences from HIV-negative normal controls in a number of measures of the retinal nerve fiber layer. This indicated a loss of retinal ganglion cells in HIVpositive patients without retinitis. HIV-positive patients with CMV retinitis were worse in most measurements than both HIV-negative controls and HIV-positive patients without CMV. CONCLUSIONS: Significant thinning of the retinal nerve fiber layer occurs in HIV-positive patients without infectious retinopathy, and there are further changes in the optic disk associated with CMV retinitis. Confocal scanning laser tomography may be of use in the diagnosis of early HIV-associated visual function loss. Ophthalmology 2000 Dec;107(12): Identifying early glaucomatous changes. Comparison between expert clinical assessment of optic disc photographs and confocal scanning ophthalmoscopy. Wollstein G, Garway-Heath DF, Fontana L, Hitchings RA. Glaucoma Unit, Moorfields Eye Hospital, London, UK. Department of Ophthalmology, Shaare Zedek Medical Center, Jerusalem, Israel. OBJECTIVE: To compare the ability of expert clinicians, using qualitative assessment of stereoscopic optic disc photographs, and confocal scanning laser ophthalmoscope imaging to discriminate between healthy persons and patients with early glaucoma. DESIGN: Comparative 7

8 instrument validation study. PARTICIPANTS: Seventy-two healthy persons and 51 patients with early glaucoma (average visual field mean deviation, -3.6 db). Early glaucoma was defined as a history of ocular hypertension and a reproducible visual field defect scoring 5 or less in the Advanced Glaucoma Intervention Study classification, regardless of optic disc appearance. INTERVENTION: Stereoscopic optic nerve head (ONH) photography and Heidelberg Retina Tomograph (HRT) imaging, (Heidelberg Engineering GmbH, Dossenheim, Germany). MAIN OUTCOME MEASURES: Ability of clinical assessment of stereoscopic ONH photographs and analysis of HRT parameters, taking into account the optic disc size, to detect early glaucomatous optic disc changes. RESULTS: The specificity of the majority opinion of five observers to detect early glaucomatous optic disc changes was 94.4%, with a sensitivity of 70.6%. Using the HRT analysis, the specificity was 95.8% and the sensitivity was 84. 3%. CONCLUSIONS: Heidelberg Retina Tomograph image analysis that takes into account the optic disc size is more sensitive than clinical assessment of stereoscopic optic disc photographs in distinguishing between healthy persons and patients with early glaucoma. Ophthalmology 2000 Dec;107(12): Glaucomatous optic disc changes in the contralateral eye of unilateral normal pressure glaucoma patients. Wollstein G, Garway-Heath DF, Poinoosawmy D, Hitchings RA. Glaucoma Unit, Moorfields Eye Hospital, City Road, London, UK. OBJECTIVE: To evaluate the optic disc for structural abnormalities in the contralateral eye of unilateral normal pressure glaucoma patients. DESIGN: Cross-sectional study. PARTICIPANTS: Fifty-three unilateral normal pressure glaucoma patients. TESTING: Optic disc imaging with the Heidelberg Retina Tomograph (HRT). MAIN OUTCOME MEASURES: Optic disc structural parameters. RESULTS: Of the contralateral (normal visual field) eyes, 79.2% were found to have an abnormal optic disc by HRT analysis. Of the glaucomatous (abnormal visual field) eyes, 94.3% were found to have an abnormal disc. The patterns of disc abnormality were defined as marked or moderate diffuse thinning of the neuroretinal rim (NRR) or broad or narrow focal thinning of the NRR. The most common pattern in the contralateral eyes was moderate diffuse thinning of the NRR (45.2%). The most frequently abnormal segments were the nasal superior (73. 8%) followed by the nasal inferior and the global NRR parameter (both 54.8%). CONCLUSIONS: A high frequency of NRR thinning was found in the contralateral (normal visual field) eyes of unilateral normal pressure glaucoma patients by HRT analysis. Knowing whether these abnormalities predict future progression to the development of visual field abnormality must wait until longitudinal studies are completed. If a disc abnormality is shown to predict future field loss, then early identification will allow early treatment. Graefes Arch Clin Exp Ophthalmol 2000 Sep;238(9): Three-dimensional analysis of measurements of the Heidelberg Retina Tomograph. Muller-Richter UD, Malig HJ, Schwerdtner A, Lang M, Hille K, Ruprecht KW. Augenklinik und Poliklinik der Universitat des Saarlandes, Homburg, Germany. BACKGROUND: With the aid of scanning laser tomography, feasible with the Heidelberg Retina Tomograph (HRT), refined structures can be measured three-dimensionally. Pictures are built up from scanned layers which are represented as two-dimensional topographical or reflectivity pictures by the HRT software. The kind of information that is provided by the third dimension can be exploited much better by real spatial three-dimensional presentation. The autostereoscopic Dresden 3D display makes such a spatial presentation feasible as add-on to the HRT. METHODS: Seventeen patients (9 women, 8 men) were chosen on the basis of a long duration of observation (mean

9 months) and a large number of follow-up examinations (mean 5.29). These patients were examined with the HRT as well as with the Dresden 3D display. The results were compared regarding their correlation pairs. RESULTS: Comparing the correlation pairs (r>0.7) the Dresden 3D display provided a higher Pearson correlation coefficient with 8 out of 10 pairs. It was evident that the evaluations of the two devices referred to the same parallel structures. DISCUSSION: The Dresden 3D display facilitates, with its form of presentation, a better evaluation of the measurements of the HRT. More precise evaluation of retinal structures by virtue of the autostereoscopic display presents an improvement. Br J Ophthalmol 2000 Sep;84(9): Use of sequential Heidelberg retina tomograph images to identify changes at the optic disc in ocular hypertensive patients at risk of developing glaucoma. Kamal DS, Garway-Heath DF, Hitchings RA, Fitzke FW. Glaucoma Unit, Moorfields Eye Hospital, London EC1V 2PD. AIM: To determine if global and segmental changes in optic disc parameters of sequential Heidelberg retina tomograph (HRT) images develop in individual ocular hypertensive (OHT) patients without white on white visual field defects. METHODS: Patients and normal controls were recruited from a prospective ocular hypertension treatment trial. The subject groups consisted of 21 OHT patients who had converted to early glaucoma on the basis of visual field criteria (24-2 program on the Humphrey perimeter), 164 OHT subjects with normal visual fields, and 21 normal controls. Sequential HRT images months apart were obtained for each subject and segmental optic disc parameters were measured to determine if any change had occurred. From the analysis of sequential HRT images of the 21 normal eyes we established normal limits of interimage variation. Individual discs in each group showing changes above the 95% limit of normal variability were then sought. RESULTS: Several segmental and global optic disc parameters were found to show significant change in the converter group before confirmed visual field change, confirming our previously published results. Individual optic disc analysis using the 95% limit of normal variability data demonstrated glaucomatous change in 13 out of 21 converter eyes. 47 of the 164 OHT eyes with normal visual fields showed change in global and segmental parameters in a "glaucomatous" direction above the level expected for normal variability. The parameters which changed most frequently in the OHT eyes were: global cup volume (6.7% of discs), inferonasal cup volume (11%), inferotemporal cup volume (8.5%), and superotemporal cup area (7.3%). CONCLUSIONS: We have identified change in a subset of ocular hypertensive patients which could predate the development of glaucomatous visual field loss. The HRT could be of value in the sequential follow up of those suspected of having glaucoma by identifying eyes at risk of developing glaucoma. However, further refinement of the technique is required to eliminate some of the inherent variability of the analysis method described, and to increase the ability to detect at risk individuals. Am J Ophthalmol 2000 Sep;130(3): Optic disk topography after medical treatment to reduce intraocular pressure. Bowd C, Weinreb RN, Lee B, Emdadi A, Zangwill LM. Glaucoma Center and Diagnostic Imaging Laboratory, Department of Ophthalmology, University of California, San Diego, La Jolla, PURPOSE: We examined changes in optic disk topography using confocal scanning laser ophthalmoscopy after reducing intraocular pressure with administration of latanoprost. METHODS: Twenty-nine patients with glaucoma or ocular hypertension were imaged using the Heidelberg Retina Tomograph before and after the administration of latanoprost to decrease intraocular pressure. Average time between pretreatment and posttreatment imaging was 2.7 +/- 1.8 weeks. 9

10 Heidelberg Retina Tomograph software-measured parameters were mean height of contour, cup area, cup volume, mean cup depth, maximum cup depth, cup shape, rim area, rim volume, cup-todisk ratio, and retinal nerve fiber thickness. RESULTS: Average intraocular pressure decreased significantly (mean +/- SD) by 7.2 +/- 5.4 mm Hg (25 +/- 16% decrease). No statistically significant changes in measured topographic parameters were found. When data from patients with decreases in intraocular pressure of 7 mm Hg or greater were analyzed separately (mean intraocular pressure decrease = / mm Hg, 36 +/- 8% decrease), cup area (P =.005), cup volume (P =. 002), and cup-to-disk ratio (P =.005) decreased significantly, and rim area (P =.005) increased significantly. Linear regression analysis of the data from all subjects showed that a change in intraocular pressure after latanoprost administration accounted for 12% or more of the variance in two measured topographic parameters (mean cup depth and cup shape). CONCLUSIONS: These results suggest that, in some patients, moderate decreases in intraocular pressure may affect disk topography, as measured by Heidelberg Retina Tomograph. Intraocular pressure should be considered when analyzing consecutive confocal scanning laser ophthalmoscopy images for glaucomatous progression. Klin Monatsbl Augenheilkd 2000 Aug;217(2):82-87 Monitoring of morphometric changes of optic discs with morphologic progression of glaucomatous optic atrophy by means of laser scanner tomography. Mardin CY, Horn F, Budde WM, Jonas JB. Augenklinik mit Poliklinik der Universitat Erlangen-Nurnberg. christian.mardin@augen.imed.unierlangen.de AIM: Aim of this study was to measure morphometric changes in optic discs with laser-scanning tomography (HRT, Heidelberg-Retina-Tomograph, Heidelberg) in eyes with early glaucomatous morphologic progression. PATIENTS AND METHODS: 61 eyes of 36 patients with marked neuroretinal rim loss or its early morphologic signs (1. optic disc hemorrhages, 2. reduced visibility of the retinal nerve fiber layer (RNF), 3. appearance of narrowing of retinal vessels, 4. enlargement of the choroidal, parapapillary atrophy) were compared to 74 normal eyes of 39 probands. 15 degrees stereographs of the optic discs were evaluated for morphologic changes. The morphometric variables of the neuroretinal rim and excavation measured by the HRT were examined in the course of the disease. RESULTS: In the group of normals no significant changes of the neuroretinal rim in the course of 2.0 +/- 1.2 years were found. In the group of glaucomatous eyes (3.0 +/- 1.5 years follow-up) 34 eyes showed marked neuroretinal rim loss, 17 disc hemorrhages, 4 vessel narrowing, 3 an increased chorioidal atrophy, 3 a decreased visibility of the retinal nerve fiber layer. In these eyes a significant loss of rim area (p = 0.01) and an increase of excavation area (p = ) and volume (p = 0.003) was measured by the HRT. Only three eyes showed a perimetric loss of sensitivity ( db) in Octopus static perimetry. CONCLUSIONS: Laser-scanning tomography of the optic disc seems to be able to measure morphometric changes in eyes with morphologic progression of glaucomatous optic atrophy, even before perimetric changes occur. Graefes Arch Clin Exp Ophthalmol 2000 Aug;238(8): Measurement of a novel optic disc topographic parameter, "spikiness", in glaucoma. Morgan-Davies J, King AJ, Aspinall P, O'Brien CJ. Visual Impairment Research Group, Heriot Watt University, Edinburgh, Scotland, UK. BACKGROUND: Structural changes in the lamina cribrosa have been implicated in the pathogenesis of glaucomatous optic atrophy, but not observed. This paper presents a novel parameter of topographic variability within the optic disc, termed "spikiness", which may reflect glaucoma-related changes in the lamina. METHODS: Four age-matched groups of normal patients 10

11 (n=12, mean age 64.8 years) and patients with ocular hypertension (n=14, mean age 63.1), primary open-angle glaucoma (n=11, mean age 70) and low-tension glaucoma (n=15, mean age 66.3) were recruited. Images of normal and glaucomatous eyes from the Heidelberg Retina Tomograph were imported into ERDAS image processing software where the spikiness data (30 consecutive mean surface height values across the base of the optic cup in both the vertical and horizontal meridians) were extracted in a format that facilitated further statistical analysis. RESULTS: Significant differences in topographic variability (spikiness) existed in the vertical (F=3.64, P=0.01) but not the horizontal meridian (F=1.25, P=0.3) through the optic disc. Spikiness was inversely related to Humphrey mean deviation (P<0.05), and cup-disc ratio (P<0.004) and was directly related to nerve fibre layer thickness (P<0.005). Of particular interest was the finding that the spikiness measure was the only optic disc parameter to significantly discriminate low tension glaucoma from primary open angle glaucoma. CONCLUSION: A new measure of surface variability (topography) at the floor of the optic cup has been described. The new index of spikiness may represent a measurement of lamina cribrosa fragility which has been implicated, but not previously estimated, in glaucomatous eyes. Automated analysis of normal and glaucomatous optic nerve head topography images. Swindale_NV; Stjepanovic_G; Chin_A; Mikelberg_FS Invest Ophthalmol Vis Sci, , 41: 7, PURPOSE: 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. METHODS: 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. RESULTS: 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). Eightyseven 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%. CONCLUSIONS: ONH images can be classified objectively and dependably by an automated procedure that does not require prior manual outlining of disc boundaries. Graefes Arch Clin Exp Ophthalmol 2000 Jun;238(6): Search for an optimal combination of structural and functional parameters for the diagnosis of glaucoma. Multivariate analysis of confocal scanning laser tomograph, blue-on-yellow visual field and retinal nerve fiber layer data. Vihanninjoki K, Teesalu P, Burk RO, Laara E, Tuulonen A, Airaksinen PJ. Department of Ophthalmology, University of Oulu, Finland. BACKGROUND: The purpose of this study was to evaluate which of the structural and functional parameters--the Heidelberg Retina Tomograph (HRT), white-on-white (W/W) and blue-on-yellow 11

12 (B/Y) visual fields and semiquantitative retinal nerve fiber layer (RNFL) scoring parameters--can give the best separation between non-glaucomatous and glaucomatous eyes. METHODS: Fifty-five subjects were included in this study: 32 nonglaucomatous subjects with mean age of 54 years, and 23 patients with ocular hypertension or glaucoma and mean age of 59 years. The HRT with software 1.11, the Humphrey 30-2 W/W and lens coloration-corrected B/Y visual fields, and semiquantitative RNFL scores were utilized. Stepwise logistic regression analysis was used in finding, from a given set of parameters, a best discriminating parsimonious subset to a logistic model, the discriminatory performance of which was evaluated by the area under the ROC curve. RESULTS: When all the structural and functional variables were considered, the RNFL total overall score gave the best separation between glaucomatous and non-glaucomatous eyes (ROC area 0.98). Without the RNFL scores and optic disc size-dependent HRT parameters in the model, the cup shape measure was selected first (ROC area 0.88). In the second step the RNFL thickness was selected (ROC area 0.91), and in the third step the corrected B/Y mean deviation (MD) was selected (ROC area 0.91). With only the HRT parameters in the model, the cup/disc ratio was selected first (ROC area 0.88). However, when the groups were matched for optic disc size, all disc size-dependent HRT variables lost their discriminant power. CONCLUSION: Cup shape measure and RNFL thickness, together with age- and lens coloration-corrected MD of the B/Y perimetry provided good discrimination between healthy individuals and patients with glaucoma. Graefes Arch Clin Exp Ophthalmol 2000 May;238(5): Development of the standard reference plane for the Heidelberg retina tomograph. Burk RO, Vihanninjoki K, Bartke T, Tuulonen A, Airaksinen PJ, Volcker HE, Konig JM. Department of Ophthalmology, University of Heidelberg, Germany. reinhard_burk@med.uniheidelberg.de BACKGROUND: Topometry of the optic disc is the quantitative assessment of the structure of the optic nerve head by means of three-dimensional parameters. The parameter values depend on definitions of intraocular reference planes. PURPOSE: To describe the development of intraocular reference planes in laser scanning tomography for the Heidelberg Retina Tomograph (HRT) using image intrinsic data with a fixed offset reference plane (320 microm) and to present a contour-linebased "flexible" standard reference plane ("SRP") for calculation of intrapapillary stereometric parameters taking the interindividual variability of optic disc topography into account. METHODS: Ten-degree triple images were obtained by laser scanning tomography from 99 glaucoma eyes and 180 normal eyes. The images were evaluated to assess the variability of height measurements of an optic disc border contour-line segment (6 degrees width) corresponding to the site of the papillomacular bundle as indicated by the average optic disc surface inclination angle. RESULTS: The average optic disc surface inclination angle was -7 degrees +/- 3 degrees below the horizontal meridian (0 degrees). The 6 degrees wide contour-line segment for the SRP was chosen according to the average surface inclination angle (-10 degrees to -4 degrees). The reproducibility of the SRPsegment height measurements was 16.0+/-10.8 microm for normal eyes and 23.4+/-18.0 microm for glaucoma eyes. To ensure that the automatic reference level determination for intrapapillary parameters remained below the disc border height, we defined the SRP level at a 50 microm offset (>2 SD of average segment height reproducibility in glaucoma) added to the individual height position of the 6 degrees contour line segment. CONCLUSION: The flexible standard reference plane allows for automatic determination of intrapapillary variables once a disc border contour line is interactively defined. In contrast to a fixed offset reference plane (e.g. 320 microm below the mean retina height), the interindividual variability of optic disc topography (oblique insertion, glaucomatous surface flattening) is respected at the cost of the need for an accurate optic disc border outline. 12

13 Measurement of peripapillary retinal nerve fiber layer volume in glaucoma. King_AJ; Bolton_N; Aspinall_P; OBrien_CJ Am J Ophthalmol, , 129: 5, PURPOSE: To measure peripapillary retinal nerve fiber layer volume in normal subjects and patients with ocular hypertension, primary open-angle glaucoma, and low-tension glaucoma. METHODS: Sixty-five subjects were classified into four groups of normal subjects and subjects with ocular hypertension, primary open-angle glaucoma, and low-tension glaucoma on the basis of intraocular pressure measurements, visual field loss, and optic disk appearance. Groups were matched for sex, age, and optic disk area. Peripapillary retinal nerve fiber layer volume measurements were made with a modification of software version 1.11 of the Heidelberg Retina Tomograph confocal scanning laser ophthalmoscope. Retinal nerve fiber layer volume measurements were taken at 0.1-mm increments from the disk margin for a global 360-degree assessment and at four predefined segments using two different reference planes. Statistical analysis was carried out using analysis of variance with Bonferroni correction. RESULTS: Retinal nerve fiber layer volume measurements showed a gradation from normal to ocular hypertension and from ocular hypertension to glaucoma groups. Mean group measurements showed statistically significant differences (P <.05) in peripapillary retinal nerve fiber layer volume for most segmental measures between the groups. Measurements with the default reference plane in the 0.0-mm to 0.1-mm and 0.1-mm to 0.2-mm increments for the superotemporal segment showed the greatest differences between groups (P <.00005). CONCLUSION: Peripapillary retinal nerve fiber layer volume measurements differ between groups of normal subjects and patients with ocular hypertension, primary open-angle glaucoma, and low-tension glaucoma. This measure offers a further method of assessment of retinal nerve fiber layer in patients with glaucoma and glaucoma suspects. Am J Ophthalmol 2000 May;129(5): Relationship between structural abnormalities and short-wavelength perimetric defects in eyes at risk of glaucoma. Ugurlu S, Hoffman D, Garway-Heath DF, Caprioli J. Glaucoma Division, Jules Stein Eye Institute, UCLA School of Medicine, Los Angeles, California, USA. PURPOSE: To determine the relative prevalence of blue-yellow perimetric defects and structural abnormalities of the optic nerve and nerve fiber layer in eyes at risk of glaucoma. METHODS: Seventy-two eyes (of 72 patients) at risk of glaucoma, with normal white-on-white full threshold perimetry, were examined prospectively with blue-yellow full-threshold perimetry (Humphrey). Structural evaluations were conducted with qualitative assessment of stereoscopic color optic disk photographs and monochromatic nerve fiber layer photographs performed independently by three masked examiners (a glaucoma specialist and two glaucoma fellows), and statistical analysis of summary parameters was obtained with scanning confocal laser tomography (abnormal defined as values outside 95% confidence limits established in normal control subjects). RESULTS: Kappa values for interobserver agreement were 0.64, 0.88, and 0.79 for optic disk evaluation and 0.59, 0.60, and 0.61 for nerve fiber layer evaluation. Thirteen (18%) of 72 eyes had blue-yellow abnormalities. A total of 30 eyes (42%) were identified as having a structural abnormality; 29 (40%) had qualitatively determined optic disk abnormalities, 21 (29%) had qualitatively determined nerve fiber layer defects, and 26 (36%) had statistically significant structural abnormalities. Twelve of 13 eyes with blue-yellow defects had a detectable structural abnormality; all 12 had abnormalities identified with disk photography, nine with nerve fiber layer photography, and 12 by scanning laser tomography. CONCLUSIONS: Clinically detectable structural abnormalities frequently coexist with blue-yellow perimetric defects in patients with ocular hypertension. A 13

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