Comparison of optic disc parameters using spectral domain cirrus high-definition optical coherence tomography and confocal scanning laser ophthalmoscopy in normal eyes Hemma Resch, Gabor Deak, Ivania Pereira and Clemens Vass Department of Ophthalmology, Medical University of Vienna, Vienna, Austria ABSTRACT. Purpose: To compare Cirrus HD optical coherence tomography (HD-OCT) with confocal scanning laser ophthalmoscopy (HRT 3) for analysis of optic disc parameters in healthy eyes. Methods: In 126 subjects, cup volume (CV), vertical cup disc ratio (CDR), neuroretinal rim area (NRA), cup area (CA) and optic disc area (ODA) were measured with the Cirrus HD-OCT and HRT 3. These optic disc parameters were chosen for statistical analysis because they can be analysed in both OCT and HRT 3 and they are widely used parameters for glaucoma assessment. Results: Mean values and significances of paired t-tests for OCT and HRT were for CV: 0.099 ± 0.11 versus 0.082 ± 0.10 (p < 0.001), CA: 0.42 ± 0.31 versus 0.39 ± 0.31 (p < 0.001), CDR: 0.36 ± 0.17 versus 0.27 ± 0.21 (p < 0.001). NRA and ODA were not significantly different between instruments. The Pearson coefficients were 0.905 (CV), 0.824 (CA), 0.734 (CDR), 0.295 (NRA) and 0.378 (ODA). Conclusion: To our interpretation, the delineation of the optic disc border is error-prone with both instruments and all parameters directly depending on it are thus poorly correlated. However, the determination of the optic disc excavation (CV and CA) appears comparable taking into account a small systematic difference between instruments. Key words: cirrus high-definition optical coherence tomography healthy subjects HRT 3 optic disc parameters Acta Ophthalmol. 2012: 90: e225 e229 ª 2012 The Authors Acta Ophthalmologica ª 2012 Acta Ophthalmologica Scandinavica Foundation doi: 10.1111/j.1755-3768.2012.02385.x Introduction Various diseases, most notably glaucoma, result in the death of retinal ganglion cells (RGC) and the degeneration of their axons. The loss of RGC axons in turn leads to a thinning of the retinal nerve fibre layer and morphological changes of the optic nerve head (ONH), which results in cupping of the optic disc. Early diagnosis and treatment have been shown to minimize the risk of visual loss owing to glaucoma. Evaluation of the optic disc is important to detect glaucomatous damage and monitor disease progression (Wollstein et al. 1998, 2000; Leung et al. 2005; Manassakorn et al. 2006; Anton et al. 2007; Naithani et al. 2007; Resch et al. 2011). The confocal scanning laser ophthalmoscope HRT 3 is a commercially available imaging instrument that provides quantitative assessment of the optic disc. Recently, high-definition optical coherence tomography (HD-OCT) has become an alternative for quantitative optic disc analysis, which has been the domain of HRT since the 90s. Clinicians with long standing experience with HRT may consider switching their glaucoma monitoring to HD-OCT. It was the aim of the present study to compare morphological optic disc parameters in healthy subjects as measured with HD-OCT and HRT 3. Cup volume (CV), optic disc area (ODA), cup area (CA), vertical cup - disc ratio (CDR) and neuroretinal rim area (NRA) were evaluated in the study because they can be analysed in both OCT and HRT 3 and they are the most widely used parameters for glaucoma assessment. e225
Subjects and Methods Subjects The study protocol was approved by the Ethics Committee of the Medical University of Vienna and followed the guidelines of Good Clinical Practice and the Declaration of Helsinki. 128 subjects of both sexes aged between 19 and 79 years were included after obtaining informed consent. Inclusion and exclusion criteria Inclusion criteria were normal ophthalmic findings, especially normal appearance of the optic disc, normal visual fields and intraocular pressure (IOP) and lack of significant retinal disorder. An abnormal visual field was defined as a glaucoma hemifield test outside normal limits and or a corrected pattern standard deviation with p < 0.05 (Keltner et al. 2003). A normal IOP was defined as 21 mmhg. Subjects with astigmatism more than +2.0 dioptres or ametropia of more than ±5.0 dioptres were excluded. Experimental paradigm Initially, a prestudy screening was carried out, where the medical and ocular history was taken. A complete ophthalmological examination was performed, including fundoscopy, visual acuity, measurement of IOP by Goldmann applanation tonometry and standard automated perimetry. One eye was selected randomly for the OCT and HRT measurements, if both eyes were eligible. The study was performed at the Department of Ophthalmology, Medical University of Vienna, general hospital. Methods Automated visual field testing was performed with the Humphrey field analyser 2 (program 30-2). Visual field eligibility criteria were <33% falsepositive responses, <33% false-negative responses, and <33% fixation losses. Optic disc morphology with HRT 3 (Heidelberg Engineering GmbH, Heidelberg, Germany; software version 1.7) was measured without pupil dilation (Heidelberg Engineering 2005). In brief, a three-dimensional topographic image consisting of 384 384 16 up to 384 384 64 pixels was constructed from multiple focal planes axially along the optic nerve head. Two series of three images each were acquired and the series with the smaller standard deviation was chosen for analysis. Images with an image quality SD >25 mm were excluded. To visualize the disc borders, the HRT images were inspected using the 3D image display. To define the contour line, six or more points were positioned at the inner margin of the scleral ring. This was carried out in consensus of three experienced operators (CV, HR and GD). Subsequently, the position of the contour line was checked again using 3D image and changed if necessary. Once the contour line was drawn, the software automatically calculated all the optic disc parameters. The reference plane is defined at 50 lm posterior to the mean retinal height between 350 and 356 along the contour line. Area above the reference is defined as the rim and below as the cup. The standard protocol and the extended parameter table were then exported for statistical analysis. With the Cirrus HD-OCT (software ver. 4.0; Carl Zeiss Meditec, Dublin, CA, USA), three individual optic disc cube 200 200 protocol scans were obtained in each subject after pupil dilatation. The available protocol used for ONH assessment was the optic disc cube. This protocol is based on a three-dimensional scan of a 6 6- mm 2 area centred on the optic disc where information from a 1024 (depth) 200 200-point voxels with an axial resolution of 5 lm is collected. To be included, all images were reviewed and had to have a signal strength >7 and the absence of movement artefacts. The OCT software detects the edge of Bruch s membrane and draws the disc outline automatically (Strouthidis et al. 2009). The following optic disc parameters measured with HRT and HD-OCT were evaluated: CV, ODA, CA, CDR and NRA. For HD-OCT, CA was calculated as difference between ODA and NRA. Statistical methods The agreement between the methods in estimating the absolute value of ODA was analysed as proposed by Bland & Altman (1986). Graphically, the difference between the measurement techniques was plotted against their mean values. Additionally, we calculated Pearson correlation coefficients and statistical significances of t-tests between the equivalent optic disc parameters measured with the two devices. Normal distribution of the data was tested using the Kolmogorov Smirnov Test. All statistical analyses were carried out with the SPSS Ò software package (IBM Corp., NY, USA) release No. 16.0.2. Results We were only able to obtain a sufficient measurement quality of 126 of 128 volunteers. Hence all data are from 126 subjects. Subjects baseline characteristics, IOP and visual field mean deviation (MD) are given in Table 1. Table 2 summarizes the mean values, the significances of t-tests and correlations of optic disc parameters measured with HRT and HD-OCT. We found significant differences between HRT and HD-OCT in paired t-tests for CV, CA and C D ratio, while ODA and NRA were not statistically significantly different. All tested variables were normally distributed. The Pearson coefficient indicated a strong correlation between instruments for CV, CA and C D ratio, whereas ODA and NRA showed only a weak, but statistically significant correlation (Fig. 1). Figure 2 demonstrates the difference in ODA between HRT and OCT in a Bland Altman plot where the pair difference was plotted against the mean value. We did not find a dependency of the differences between the methods on their respective means (linear regression analysis not significant). Table 1. Subjects baseline characteristics, IOP and visual field MD. Age (years) 37.2 ± 18.3* Sex (female male) 61 65 Refractive error (dioptres) +0.079 ± 1.48* IOP (mmhg) 14.5 ± 2.2* MD (db) )0.20 ± 1.09* *Results are presented as means ± standard deviation (SD), (n = 126). db = decibel; IOP = intraocular pressure. e226
Table 2. Optic disc parameters measured with HRT and HD-OCT and their correlations. Mean values (±standard deviation) and significances of t-tests Variable Discussion HRT (carried out in consensus of three readers) In clinical practice, of the various screening devices for optic disc analysis in glaucoma HD-OCT and HRT and their algorithms have received the most attention. These useful adjunct methods support clinicians in their clinical routine through providing complementary information that may facilitate the detection of glaucoma and its progression over time (Harasymowycz et al. 2005). Common measurement techniques, such as scanning HD-OCT Optic disc area 1.99 ± 0.44 1.98 ± 0.50 0.378* Cup volume 0.082 ± 0.10 0.099 ± 0.11 0.905* Cup area 0.39 ± 0.31 0.42 ± 0.31 0.824* C D ratio 0.27 ± 0.21 0.36 ± 0.17 0.734* Rim area 1.61 ± 0.36 1.56 ± 0.49 0.295* Pearson correlation coefficient Correlation (R 2 )of HD-OCT and HRT Data are presented as mean (±standard deviation) and are in square millimetres (areas) and cubic millimetres (volume). * Significances of correlations between optic disc parameters measured with Heidelberg Retina Tomography (HRT), and Cirrus HD-Optical Coherence Tomography (HD-OCT). p < 0.005 for optic disc area, p < 0.001 for cup volume, p < 0.001 for cup area, p < 0.001 for cup-todisc area ratio and p < 0.001 for rim area. Significances of paired t-tests between optic disc parameters measured with Heidelberg Retina Tomography (HRT), and Cirrus HD-Optical Coherence Tomography (HD-OCT). p < 0.001 for cup volume, p < 0.001 for cup area, p < 0.001 for cup-to-disc area ratio. laser ophthalmoscopy and scanning laser polarimetry, outperform most ophthalmologists in diagnostic accuracy (Reus et al. 2010). Because of the different instrumentations and imaging principles, it is uncertain if HRT 3 and Cirrus HD- OCT are comparable in measuring optic disc parameters. We found a strong correlation for the CV, CA and CDR between the two instruments despite a systematic difference in measured values. As opposed to this ODA and NRA showed only a weak correlation without a systematic difference. The results appear to reflect the difficulties, inaccuracies and differences of optic disc border determination of HRT 3 and Cirrus HD- OCT. (Fig. 1). Factors responsible for inaccuracies of the rim and disc area determination, however, may be different between HRT 3 and OCT (Saarela et al. 2010). It has been demonstrated that differences in the position of the reference plane in relation to the optic disc margin (reference height) and the image quality SD were related to rim area variability in HRT 3 (Tan et al. 2003; Strouthidis et al. 2005). HRT constructs a topographic image of the optic disc by scanning multiple focal planes axially along the optic nerve head. Each pixel is assigned a depth value according to the luminance profile across the focal planes, assuming that the maximum reflection originates from the surface of the retina and the optic nerve. Thus, despite acquisition of 3D data, HRT does not provide information on deeper tissue structures, and might even in case of low surface reflectivity provide wrong information of the retinal surface. In contrast, Cirrus HD-OCT measurements provide true 3D data of reflectivities of the different structures within the retina and the optic nerve Fig. 1. Correlations of optic disc parameters between the two measurement techniques. e227
Fig. 2. Bland Altman Plot of differences in optic disc area measurements between HDoptic coherence tomography (OCT) and confocal scanning laser ophthalmoscopy (HRT 3). The mean difference is represented by the solid line and the 95% confidence limits by the dotted lines. The linear regression analysis was not statistically significant (p > 0.05). head. From these data, proprietary algorithms of image analysis determine the margin of the optic disc and also the margin between the neuroretinal rim and the excavation is extracted. Iliev et al. (2006) compared optic disc parameters measured with the Stratus-OCT and HRT 2. Both automatic and manual OCT measurement resulted in larger ODA, NRA and RV compared to HRT. Analysis of agreement indicated important discrepancies between instruments and comparisons showed a large variance of measurement differences. This led the authors to the conclusion that optic disc morphometric parameters as determined with Stratus-OCT and HRT are not interchangeable. In another study, Schuman et al. (2003) compared the measurement of optic disc parameters obtained with HRT 1 and OCT 2 and 3. They reported that the OCT-measured mean disc area was significantly larger than that measured by HRT, as were all other disc size-related parameters. HRT and OCT measurements were highly statistically significantly correlated, but agreement and CIs were not reported which constitute a limitation of their conclusion. Similar results came from Hoffmann et al. (2005) when comparing HRT 2 and Stratus- OCT. The studies of Iliev et al. (2006), Schuman et al. (2003) and Hoffmann et al. (2005) used time domain OCT (TD-OCT) for comparison. This instrument provided only six radial scans for determination of the optic disc morphology, thus resulting in limited information about the optic disc. As opposed to this, we are the first to present a comparison of HRT 3 and Cirrus HD-OCT. While HD- OCT provides much more detailed information about the optic disc compared to TD-OCT, we nevertheless report considerable differences between HD-OCT and HRT 3 measurement of the optic disc. Possible reasons for the discrepancies, concerning the comparison of ODA between OCT and HRT in literature and also for our data, comprise the subjective nature of disc margin determination with HRT and the evolving technology of OCT. Both image resolution of OCT and algorithms for automatic disc margin detection have been subject of continuous development in the recent years. Iester et al. (2009) investigated the influence of the contour line position on the HRT parameters by drawing a contour line and increasing and decreasing radius size of 0.05 and 0.1 mm, mimicking inaccurate delineation of the optic disc border. They have shown that among the measured variables, NRA was the most sensitive to the changes of ODA, while CA and CV were not significantly affected. These data are in accordance with the results we present in our paper, where NRA was only weakly correlated, whereas CV and CA showed a strong correlation between HRT and HD- OCT. In the present study, as for the manual delineation of the optic disc margin in HRT 3, which is sometimes difficult even for experienced observers, we have made all possible efforts to reduce errors by the process of a consensus of three experienced examiners. It is our interpretation that both the automatic delineation (HD-OCT) and the manual delineation of the optic disc border (HRT) are errorprone. However, the determination of the optic disc excavation appears to be comparable between the devices, although a small systematic difference (HD-OCT measuring 0.019 lm 3 larger CV) has to be taken into account. Conflict of Interest None declared. References Anton A, Moreno-Montañes J, Blázquez F, Alvarez A, Martín B & Molina B (2007): Usefulness of optical coherence tomography parameters of the optic disc and the retinal nerve fiber layer to differentiate glaucomatous, ocular hypertensive, and normal eyes. J Glaucoma 16: 1 8. Bland JM & Altman DG (1986): Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1: 307 310. Harasymowycz P, Kamdeu FA & Papamatheakis D (2005): Screening for primary open-angle glaucoma in the developed world: are we there yet? Can J Ophthalmol 40: 477 486. Heidelberg Engineering (2005): Heidelberg retina tomograph glaucoma module. Operating instructions software version 3.0. Heidelberg, Germany: Heidelberg Engineering. Hoffmann EM, Bowd C, Medeiros FA, Boden C, Grus FH, Bourne RR, Zangwill LM & Weinreb RN (2005): Agreement among three optical imaging methods for the assessment of optic disk topography. Ophthalmology 112: 2149 2156. Iester M, Mariotti V, Lanza F & Calabria G (2009): The effect of contour line position on optic nerve head analysis by Heidelberg Retina Tomograph. Eur J Ophthalmol 19: 942 948. Iliev ME, Meyenberg A & Garweg JG (2006): Morphometric assessment of normal, suspect and glaucomatous optic disks with Stratus OCT and HRT II. Eye 11: 1288 1299. Keltner JL, Johnson CA, Cello KE, Edwards MA, Bandermann SE, Kass MA, Gordon MO & Ocular Hypertension Treatment Study Group (2003): Classification of visual field abnormalities in the ocular hypertension treatment study. Arch Ophthalmol 121: 643 650. Leung CK, Chan WM, Hui YL, Yung WH, Woo J, Tsang MK & Tse KK (2005): Analysis of retinal nerve fiber layer and optic nerve head in glaucoma with different reference plane offsets, using optical coherence tomography. Invest Ophthalmol Vis Sci 46: 891 899. Manassakorn A, Nouri-Mahdavi K & Caprioli J (2006): Comparison of retinal nerve fiber layer thickness and optic disk algorithms with optical coherence tomography to detect glaucoma. Am J Ophthalmol 141: 105 115. Naithani P, Sihota R, Sony P, Dada T, Gupta V, Kondal D & Pandey RM (2007): Evaluation of optical coherence tomography and heidelberg retinal tomography parameters in detecting early and moderate glaucoma. Invest Ophthalmol Vis Sci 48: 3138 3145. Resch H, Schmidl D, Hommer A et al. (2011): Correlation of optic disc morphology and ocular perfusion parameters in patients with primary open angle glaucoma. Acta Ophthalmol 89: e544 e549. e228
Reus NJ, Lemij HG, Garway-Heath DF et al. (2010): Clinical assessment of stereoscopic optic disc photographs for glaucoma: the European Optic Disc Assessment Trial. Ophthalmology 117: 717 723. Saarela V, Falck A, Airaksinen PJ & Tuulonen A (2010): Factors affecting the sensitivity and specificity of the Heidelberg Retina Tomograph parameters to glaucomatous progression in disc photographs. Acta Ophthalmol [Epub ahead of print]. Schuman JS, Wollstein G, Farra T, Hertzmark E, Aydin A, Fujimoto JG & Paunescu LA (2003): Comparison of optic nerve head measurements obtained by optical coherence tomography and confocal scanning laser ophthalmoscopy. Am J Ophthalmol 135: 504 512. Strouthidis NG, White ET, Owen VM, Ho TA, Hammond CJ & Garway-Heath DF (2005): Factors affecting the test-retest variability of Heidelberg retina tomograph and Heidelberg retina tomograph II measurements. Br J Ophthalmol 89: 1427 1432. Strouthidis NG, Yang H, Fortune B, Downs JC & Burgoyne CF (2009): Detection of optic nerve head neural canal opening within histomorphometric and spectral domain optical coherence tomography data sets. Invest Ophthalmol Vis Sci 50: 214 223. Tan JC, Garway-Heath DF, Fitzke FW & Hitchings RA (2003): Reasons for rim area variability in scanning laser tomography. Invest Ophthalmol Vis Sci 44: 1126 1131. Wollstein G, Garway-Heath DF & Hitchings RA (1998): Identification of early glaucoma cases with the scanning laser ophthalmoscope. Ophthalmology 105: 1557 1563. Wollstein G, Garway-Heath DF, Fontana L & Hitchings RA (2000): Identifying early glaucomatous changes. Comparison between expert clinical assessment of optic disc photographs and confocal scanning ophthalmoscopy. Ophthalmology 107: 2272 2277. Received on June 20th, 2011. Accepted on January 6th, 2012. Correspondence: Clemens Vass, MD Department of Ophthalmology and Optometry Medical University of Vienna, General Hospital Währinger Gu rtel 18-20 A-1090 Vienna Austria Tel: ++43-1-40400-7900 Fax: ++43-1-40400-7902 Email: clemens.vass@meduniwien.ac.at e229