Glaucoma is the most common cause of irreversible blindness worldwide and the most common optic neuropathy.1 Increasing evidence shows that alterations in the optic nerve head (ONH) are the earliest signs of glaucoma,2 and examination and documentation of the optic disk and retinal nerve fiber layer (RNFL) are essential for diagnosing and monitoring of glaucoma. Stereoscopic optic disk photography is the gold standard for evaluating the optic nerve changes during glaucoma, but it could not provide quantitative measurements. Hence, several imaging technologies such as confocal scanning laser ophthalmoscopy (Heidelberg retina tomograph (HRT)), scanning laser polarimetry, and optical coherence tomography (OCT) are introduced for clinical evaluation of optic nerve. HRT imaging of the ONH has been available commercially for around 20 years, providing objective and reproducible analysis of ONH morphmetric parameters. It has been proved highly reproducible and shows good agreement with clinical estimates between optic nerve head structure and visual function.3–6
OCT is another imaging modality that obtains high-resolution cross-sectional images of the retina and ONH. A recent developed technology named spectral-domain OCT (SD-OCT) acquiring data in the Fourier domain offers sensitivity and speed-advantages over other standard OCT techniques working in the time domain, thereby making possible in vivo real-time, 3 dimensional and ultra-high resolution imaging of retina and ONH. There are many reports comparing Cirrus high definition-OCT (one of SD-OCT) and HRT-3, wheras no data show the agreement between HRT3 and Copernicus OCT (SOCT), one of the SD-OCT currently available commercially. The purpose of this study was to evaluate the agreement between ONH parameter measurements generated by SOCT and HRT-3.
A total of 44 healthy normal volunteers were recruited in this study. One eye of each subject was selected randomly by drawing lots. All subjects underwent a full ophthalmic examination including visual acuity, refraction, intraocular pressure measurement by Goldmann tonometry, and dilated fundus examination by stereoscopic biomicroscopy of the ONH by slit lamp and indirect ophthalmoscopy. The inclusion criteria were best corrected visual acuity no worse than 20/40 and spherical refractive error within the range of -6.00 to +3.00 D. Subjects were excluded if they had a history of any retinal disease, surgery or laser procedures, diabetes mellitus, hypertension, or neurologic diseases. In particular, they had no structural optic disc abnormalities and no history of intraocular pressure higher than 21 mm Hg. The measurements were done sequentially using confocal scanning laser ophthalmoscope (HRT-3, software v3.1.2, Heidelberg Engineering, Germany) and SOCT (SOCT Copernicus HR; OPTOPOL Technology S.A., Poland). The study was conducted in accordance with the ethical standards stated in the 1964 Declaration of Helsinki and approved by Nanjing Tongren Hospital Clinical Research Ethics Committee with informed consent obtained.
The HRT-3 is a confocal scanning laser ophthalmoscope utilizing a diode laser source with a wavelength of 670 nm. The spherical equivalent refractive error of each eye was adjusted in the dipodic ring of the HRT. After keratometric readings were entered into the software, topographic images were obtained and analyzed using HRT 3.1.2 software. Good quality images were checked with the image acquisition quality control. The margin of the optic discs was manually traced by the same researcher. The standard reference plane is defined as 50 μm posterior to the mean retinal surface indicated by the contour line at the disc margin between 350° and 356°. The following HRT-3 ONH parameters were recorded: disc area, cup area, rim area, cup/disc ratio, cup volume and disc volume.
Disc examination mode and 3D scan pattern were chosen. Subjects were positioned before SOCT and OCT images were acquired. Images with quality index (QI) values above 6 mean good quality and were selected for analysis. Disc parameters such as disc area, cup area, rim area, cup/disc ratio, cup volume and disc volume were used in the comparisons of ONH topography parameter measurement and agreement with HRT-3.
Statistical analyses were performed using SPSS 11.0, (SPSS Inc., USA). A paired t test was used to determine statistical differences between the mean measurements obtained by the two instruments. The Pearson correlation test was used for assessing the relation between measurements of ONH parameter obtained by SOCT and HRT-3. Bland-Altman plot was used to assess agreement between SOCT and HRT-3 measurements. P<0.05 was considered statisitically significant.
A total of 44 eyes of 44 subjects were examined in this study. All recruited subjects were examined during the period of April 2010 in the Nanjing Tongren Hospital. Table 1 shows the demographic data of the subjects. The mean age of the subjects was (29.5±8.8) (range 17-60) years.
The various ONH parameters evaluated by SOCT and HRT-3 are shown in Table 2. There was no significant difference in the average cup area (0.306 vs. 0.355 mm, P=0.766), cup volume (0.158 vs. 0.130 mm, P=0.106) and cup/disc ration (0.394 vs. 0.349 mm, P=0.576) measured by the two instruments. However, the average disc area (1.435 vs. 2.466 mm, P=0.0005), rim area (1.111 vs. 2.111 mm, P=0.001), rim volume (0.122 vs. 0.707 mm, P=0.000) from SOCT were significantly lower compared with those from HRT-3. The Bland-Altman plots between SOCT and HRT-3 optic disc parameters measurements are shown in Figure 1. The Bland-Altman plots revealed good agreement of cup area and cup volume measured by SOCT and HRT-3. Bad agreement of disc area, rim area, rim volume and cup/disc ratio were found between SOCT and HRT-3. The highest correlations between the two instruments are observed for cup area (r2=0.783, P=0.000) and cup/disc ratio (r2=0.669, P=0.000), whereas the lowest correlations are observed for disc area (r2=0.100, P=0.037), rim area (r2=0.275, P=0.000), cup volume (r2=0.005, P=0.391), rim volume (r2=0.021, P=0.346) (Figure 2).
OCT is a high-resolution imaging device that uses interferometry to analyze reflectivity changes between adjacent structures, and that can measure the ONH parameters and RNFL thickness in vivo. Most importantly, the ONH and RNFL image acquired by OCT correlates well with histology.7,8 Before SD-OCT was introduced into clinical use, time-domain OCT (TD-OCT), especially Stratus OCT (Carl Zeiss Meditec, Dublin, CA, USA), was widely employed to evaluate ONH parameters and RNFL thickness, whose good reproducibility was observed.9–14 However, the slow scan speed of the Stratus OCT could result in test errors because of eye movement during the examination and less scan lines reconstructing the ONH could not provide enough information for ONH analysis. Unlike TD-OCT, which uses a point detector or photodetector in the detector arm, the new generation SD-OCT uses a spectrometer as the detector that is capable of an acquisition speed of up to 55000 A scans per second, in contrast to 512 A scans in 1.3 seconds for TD-OCT,15,16 with resolution being up to ten times higher and imaging speed up to 60 times faster than in conventional TD-OCT.17 Superior acquisition and higher resolution of SD-OCT has progressively replaced other ONH imaging tools. Since clinicians have long standing experience with HRT, it is important to know the agreement between the two instruments before they switch their glaucoma monitoring to SD-OCT.
The SOCT, developed by Optopol (Zawiercie, Poland), is one of SD-OCT, offers a complete glaucoma module, including an RNFL thickness analysis and ONH analysis. Different from other SD-OCT, based on ONH measurements, SOCT provide a disc damage likelihood scale (DDLS) to grade glaucoma optic neuropathy, which is introduced by Spaeth et al.18 Until now there are no reports on relationship about SOCT and HRT, this study compared ONH measurements obtained by SOCT and HRT-3 and evaluated their correlation with each other.
From the results, Bland-Altman plots show good agreements of cup area and cup volume between the two instruments, while bad agreements of disc area and disc volume, which lead to bad agreements of other optic nerve parameters such as rim area, rim volume and cup/disc ratio that all derived from cup and disc measurements. Paired-t test and Pearson correlation test results are consistent with Bland-Altman plots. Disc parameters measured by SOCT were smaller than those by HRT-3.
The difference between the two instruments may come from the different determinations of the reference planes level of cup and disc. With the HRT-3, the delineation of disc margins remains a challenge for the accurate measurement of optic disc area. In HRT-3 software, the optic disc margins should be manually determined in order to obtain the ONH parameters, and the default reference plane is set 50 μm below the mean retinal surface indicated by the contour line at the disc margin between 350° and 356°. The reference plane in SOCT is determined by automatic identification of the end of retinal pigment epithelium around the optic nerve. Therefore the two reference planes are not the same plane.
Based on our results, the measurements of ONH parameters as determined by SOCT and HRT-3 are not interchangeable. Otherwise, we can get different diagnostic conclusions regarding the same eye only because different devices are used. This conclusion is consistent with previous studies on other SD-OCT. Foo et al19 have compared the agreement between Cirrus OCT (one of SD-OCTs, Carl Zeiss Meditec, Dublin, California, USA) and HRT-3, showing no difference in mean optic disc area measurements and smaller rim area, but bigger cup-related parameters than HRT-3. The Bland-Altman plots demonstrated significant proportional bias for differences in all ONH parameters which indicated disagreements between the two instruments. Studies by Resch et al20 and Sato et al21 have supported the conclusions of disagreements of Cirrus OCT and HRT-3. Different disc and cup margin confirmation methods were believed to be the main reason for that.
In summary, measurements of ONH parameters with SOCT and HRT-3 are not interchangeable in the diagnosis and follow up of glaucoma. Attention should be paid on the interpretation of ONH parameters obtained from different measurement methods.
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