Comparison of Spectralis and Cirrus spectral domain optical coherence tomography for the objective morphometric assessment of the neuroretinal rim width

Glaucoma is defined as an optic neuropathy with progressive loss of retinal ganglion cells and associated morphological changes to the optic nerve and retinal nerve fiber layer (RNFL), respectively [1]. Loss of visual function in glaucoma is generally irreversible and, without adequate treatment, the disease can lead to visual impairment or blindness [1]. Morphological damage may precede a loss of function by many years, and precise imaging techniques are fundamental for a detection of progression, especially at earlier stages of damage [2]. Next to assessing the visual field, diagnosis and management of glaucoma are based on the detection of morphometric changes to the optic nerve head (ONH) and peripapillary RNFL for years in the progress of the disease. Using spectral domain optical coherence tomography (SD-OCT), the configuration of the ONH and the thickness of the peripapillary RNFL can be objectively measured [3]. Change over time in RNFL thickness, measured with a circular peripapillary SD-OCT scan pattern, is widely accepted as a marker for progression of glaucomatous optic neuropathy. Still, it is limited by imaging artifacts, which influence the correct segmentation of the RNFL and may to some extent be consequences of decreased OCT reflectivity in glaucoma [4]. Recently, another anatomic SD-OCT biomarker describing the neuroretinal rim anatomy gained clinical importance and in some studies proved to surpass other parameters in the diagnostic power for glaucoma [5‐10]. Two widely used SD-OCT devices, the Spectralis® spectral domain optical coherence tomograph (Heidelberg Engineering GmbH, Heidelberg, Germany) and the Cirrus® high-definition optical coherence tomograph (Carl Zeiss Meditech Inc., Dublin, CA, USA) offer the possibility of quantifying the neuroretinal rim width (NRW). Having introduced those measurements into our clinical practice some years ago, we learned that the reports of the Cirrus OCT (which include exemplary b-scans showing the limits of the NRW measurements) did not correspond in detail with Spectralis OCT assuming the same segmentation and algorithm for measuring the NRW. We recognized that the ILM-sided limits of the vector connecting the ILM and the Bruch’s membrane opening (BMO) of the Cirrus OCT often were at different locations than those of the Spectralis OCT and apparently not at the ILM intersection the Spectralis OCT algorithm would have provided. Upon investigating, Carl Zeiss Meditec USA provided us with a US patent paper which, among other aspects, explains the algorithm used by the Cirrus OCT for the determination of the NRW [11]. Cirrus NRW is not optimized for the smallest distance, but for the smallest cross-sectional area of the RNFL at the optic disc. Refer to the “Methods” section of this article for details. Thus, concerning the Cirrus OCT and the Spectralis OCT, we are confronted with two rather different algorithmic approaches to determining the NRW.

To our knowledge, at present time, no study focused on comparing NRW measurements taken with those two devices. Hence, the aim of this study was to assess the comparability of NRW measurements of the Cirrus OCT and the Spectralis OCT.

Table 1 shows a summary of the baseline characteristics. We included 20 eyes of patients with glaucoma (mean age 71.18 ± 6.05 years), and 20 eyes of healthy subjects (age 65.48 ± 8.13 years). Image quality of OCT scans was within the range recommended by the manufacturers in all cases.

We systematically compared the MRW measurement results of two widely used SD-OCT devices (Carl Zeiss Meditec™ Cirrus HD-OCT® and Heidelberg Engineering™ Spectralis SD-OCT®) for a group of 20 glaucoma patients and a control group of 20 healthy subjects. For healthy subjects, Cirrus mean NRW were markedly higher than Spectralis mean NRW, on average by 91 μm. The difference between devices increased with higher mean NRW values and was especially pronounced for the nasal quadrant (158 μm). On the contrary, for glaucoma patients, NRW was comparable between Cirrus and Spectralis OCT. The causes of the marked differences in healthy subjects may lie in segmentation algorithms, the NRW calculation algorithm itself, and properties concerning scan acquisition and registration.

When comparing healthy subjects and glaucoma patients, our measurements correspond well to results in literature, such as Reis et al. who reported Spectralis OCT-performed NRW measurements of 329 μm for healthy subjects and 176 μm for glaucoma patients [13].

In the current study, Pearson correlations between Spectralis and Cirrus NRW measurements in individual quadrants and for the whole circumference were very strong (all quadrants r > 0.8, global NRW r = 0.949) and of high statistical significance (all p < 0.001), for either the native Spectralis dataset or the Spectralis AIF dataset. This seems natural for two devices measuring the same quantity. In their comparison of RNFL thickness measurements with Spectralis OCT and Cirrus OCT, Faghihi et al. reported higher RNFL thickness values with the Spectralis OCT compared with the Cirrus OCT (mean difference was 4.67 ± 6.55 μm, p < 0.001) and a strong inter-measurement correlation of r = 0.912 with p < 0.001 [14]. Comparable results were also reported by other groups [15, 16]. However, to the best of our knowledge, for the NRW this has not yet reported before.

A transformation model between NRW of both devices was rendered, showing that Cirrus shows higher values than Spectralis for mean measurements being higher than 159 μm (see Fig. 2). Although the correlation of this model was very strong, the applicability is limited because it is based on values of the whole circumference and one may be rather interested in values at a specific angle, which may be quite different from the mean across all angles. Furthermore, our models allowed for prediction of NRW across instruments with 53.88 μm (Cirrus NRW calculated based on Spectralis NRW) and 31.11 μm (Spectralis NRW calculated based on Cirrus NRW) residual standard error and prediction intervals of 299 ± 110 μm for the Cirrus NRW and 249 ± 68 μm for the Spectralis NRW which will be unacceptable in clinical routine. Furthermore, the given prediction interval is for the mean NRW across patients, and would be even larger for NRW at specific angles.

ROC analysis of NRW revealed both devices and their calculation methods to be excellent classifiers. Given the larger differences between healthy and glaucomatous subjects for the Cirrus as compared with the Spectralis OCT, we might have expected a better discriminatory power for the former. However, this larger difference was counteracted by larger variation for the Cirrus OCT and consequently our ROC analysis did not prove any difference in diagnostic discrimination.

Anyhow, the value of this cross-sectional discrimination capacity continues to be rather academic, as glaucoma diagnosis is multimodal and still largely based on progression detection, and the translational potential of results of case-controlled studies is limited [17]. Furthermore it should be noted that we had included on average moderately advanced glaucoma patients, which improves the diagnostic separation.

The rotational reference difference between devices had only a minor impact on localized NRW values. Our analysis showed that not much effect could be expected solely based on this difference. Only 3.4% of all tested individual NRW values differed by more than 20% between the native value and the computed AIF value. This is less than previously reported by He et al., who found that 10.8% of 222 eyes demonstrated a 20% difference in MRW in their study, which was based on manual delineation [18].

We tested the association of different covariates with the NRW measurements. The CDR as estimated in biomicroscopical examination is a simplified, dimensionally reduced estimation of NRW. Although estimated manually and being prone to subjectivity and human error, it is a morphometric parameter known to increase with the progression of retinal ganglion cell loss in glaucoma. This parameter showed a very strong correlation with NRW acquired with both devices, and performed very similar to the CRW, which takes the ODD into account. This confirms the ODD independency of OCT-based NRW measurements Enders et al. reported recently [5]. Both tested visual field defects, namely the MD and the PSD were also highly correlated with NRW. This is consistent with reports found in literature, such as the study published by Muth et al., where Spectralis OCT global NRW strongly correlated with visual field indices (r = 0.68873 with MD, and r = 0.68873 with PSD, both highly significant) [19].

There are several limitations to our study. A primary issue is the small sample size, but that is in line with other recent approaches. Nevertheless, elaborated differences and correlations mostly show high statistical significance; thus, a generalization is possible. The high ROC values are expected for comparison of moderate to severe glaucoma with healthy subjects and do not indicate an outstanding diagnostic performance. Surprisingly, we found the numerically largest difference in NRW between healthy subjects and glaucoma patients in the nasal quadrant; this was found only in Cirrus OCT. It should be noted however that this quadrant also results in the largest variation in Cirrus OCT and the distribution of values was markedly skewed. The nature of this finding remains unclear, but might be caused by the larger blood vessels together with the specific procedure of segmentation by Cirrus software. This is an exploratory study and our results are preliminary. A solid transformation model needs to be based on the measurements of much bigger patient and control cohorts.

As well as other established functional and morphometric features considered over the course of an often life-long management of glaucoma patients, the NRW will highly likely exhibit its true diagnostic potential when assessed longitudinally. NRW may be used not only in ophthalmological situations, but also others, such as cases with increased intracranial pressure; thus, detailed knowledge about the way this parameter is measured and how measurements differ between devices is quite valuable [20].We analyze the results of this rather novel objective morphological parameter, as measured by two different devices, which apply considerably differing approaches for its determination. Differences between both devices were much lower and statistically not significant for glaucoma patients, but markedly higher and statistically significant for healthy patients and the whole cohort. It may thus be recommended to compare Spectralis and Cirrus NRW measurements very cautiously and if so then only in patients with morphologically manifest glaucoma. For detailed morphological progression analysis, our results suggest the continuous usage of the same device.