Reproducibility of any diagnostic test is important both for diagnostic accuracy and for monitoring changes in disease status. In the case of glaucoma, reproducibility is critical if one is going to use an instrument to monitor for progression. One of the frustrations with the use of visual field testing to detect glaucoma progression is the long-term fluctuation of results.17
Although serial optic disc photography can be used to monitor for glaucoma progression, the subjective nature of the interpretation can make it difficult to be certain that progression has occurred.18
OCT is a relatively new technology that is being used clinically to help with the diagnosis of glaucoma and the determination of glaucoma progression, primarily through measurements of RNFL. Improvements in this technology, including SD-OCT, have made it possible to measure ONH parameters as well. Although other studies have been published on the reproducibility of RNFL thickness using SD-OCT, the uniqueness of the present study lies in the fact that it reports for the first time the repeatability and reproducibility not only of RNFL, but also of ONH parameters using the Cirrus HD-OCT 5.0 software in glaucoma patients. This new software version incorporates an algorithm for the measurement of ONH parameters, and the automatic circle placement uses the center of the new disc segmentation, making it even more reliable for RNFL measurements compared with older versions. In addition, our study design (multiple measurements over 5 days), study group (glaucomatous eyes), and parameters tested (RNFL and ONH parameters) make this study unique and adds value to the reproducibility studies on RNFL in normal eyes that have been published using SD-OCT to date. In addition, this is the first study to compare Cirrus HD-OCT RNFL and ONH reproducibility in glaucomatous eyes, which is valuable information when deciding which parameters might be most useful for monitoring glaucoma progression. As such, we believe the results are worth reporting.
The present study found excellent intravisit and intervisit reproducibility of RNFL measurements based on ICCs, CV, and TRT SD. Leung et al.10
evaluated the repeatability and reproducibility of peripapillary RNFL measurements obtained with Cirrus HD-OCT in 97 normal and 83 glaucomatous eyes and reported similar results. However, it should be noted that their intervisit measurements were obtained on only two separate occasions. The intravisit and intervisit ICC values were all greater than 80%, and CVs were generally <10%. Comparable findings for intravisit reproducibility were also reported by Gonzalez-Garcia et al.,8
who assessed the repeatability of RNFL with SD-OCT (RTVue; Optovue, Inc.) in 60 eyes from subjects without glaucoma and 38 eyes from subjects with glaucoma. The temporal quadrant had the lowest ICC 86% and the highest CV (4.72%), whereas average RNFL had the highest ICC (97%) and the lowest CV (1.9%). Our intravisit ICC, CV, and TRT SD values were similar to those reported by Vizzeri et al.12
in glaucomatous eyes. In both studies, clock hours 3, 4, and 9 showed lower ICCs compared with other parameters. Garas et al.7
used the CV to assess the intravisit reproducibility of peripapillary RNFL thickness measured with SD-OCT (RTVue; Optovue, Inc.) in 37 eyes, including 14 normal or ocular hypertensive eyes and 23 eyes with moderate to severe glaucoma. CVs for average and quadrants RNFL thickness were all <10% in eyes with moderate to severe glaucoma. A study by Kim et al.9
on the intravisit variability of RNFL thickness measurements with Cirrus HD-OCT using two different methods of ONH centering in 14 normal eyes found an ICC of 98.4% for average RNFL thickness and ICCs <90% in half of sectoral measurements. Average RNFL thickness also performed better than all other RNFL thickness parameters. Overall, it appears that average RNFL showed the highest or one of the highest ICCs, the lowest CV, and lowest TRT SD across studies. From a practical standpoint, this suggests that average RNFL thickness rather than sectoral RNFL thickness may be the best RNFL parameter for monitoring glaucoma progression.
We also found that all measurements of ONH parameters showed excellent intravisit and intervisit reproducibility using Cirrus HD-OCT. There were no differences between intravisit and intervisit ICCs. Our intravisit results agree with those recently reported for SD-OCT (RTVue; Optovue, Inc.) by Gonzalez-Garcia et al.,8
though their CVs were greater than 10% for cup area, rim volume, cup volume, and CDR. The reproducibility of OCT ONH measurements has been previously evaluated with TD OCT and yielded variable results.2–6
Paunescu et al.5
examined 10 young healthy subjects and found that the CDR and VCDR showed the best ICCs of 97% and 90%, respectively, whereas disc area and vertical integrated rim width showed the worst ICCs of 52% and 51%. However, they failed to specify whether these ICCs were for intravisit or intervisit measurements. In another study by Kamppeter et al.2
involving 10 healthy subjects, ONH measurements showed relatively good reproducibility, with the vertical integrated rim area having the lowest CV and the cup area and disc area the highest. Olmedo et al.4
evaluated the reproducibility of ONH parameters in 10 normal and 10 glaucomatous eyes. They observed that ICCs for normal eyes were greater than 81% for all parameters, but disc area (64.7%), rim area (33.3%), and horizontal integrated rim area (23.1%) had relatively poor reproducibility. ICCs in glaucomatous eyes ranged from 85.4% to 95.2%, except for disc area (68.1%). No significant differences in reproducibility were found between normal and glaucomatous eyes. Pueyo et al.6
compared the reproducibility of ONH measurements in 32 healthy, 41 ocular hypertensive, and 33 glaucoma subjects. High reproducibility, with CVs <10%, was observed for disc area, cup area, CDR, horizontal CDR, and vertical CDR, whereas rim area, vertical integrated rim area, and horizontal integrated rim width were less reproducible. More recently, Lin et al.3
found ONH measurements to be highly reproducible, with ICCs ranging between 86% and 95.9%, with the exception of disc area (73%). It should be noted that unlike Stratus OCT–based reports showing low reproducibility of disc area measurements and variable results with regard to the other parameters, both the study by Gonzalez-Garcia et al.8
using SD-OCT (RTVue; Optovue, Inc.) and the present study found that disc area measurement is as reproducible as other ONH and RNFL parameters. Disc area is a weak risk factor for glaucoma and is not influenced by IOP level or extent of glaucomatous damage.19
Therefore, it does not change as glaucoma progresses. Its clinical relevance in determining glaucoma progression is likely to be weak irrespective of its reproducibility. However, because rim area, CDR, VCDR, HCDR, VRT, and HRT are directly dependent on disc area, it is essential that disc area measurements be highly reproducible. Variability in disc area may indicate failure to correctly find and delineate the disc margin, as previously reported with the Stratus OCT ONH analysis algorithm.20,21
The Stratus OCT algorithm uses a default reference plane located 150 μm above the level of the RPE to define the cup margin. The drawback to this method is that the reference plane is not stable, so that the default reference plane may be above the “actual” reference plane in optic discs with significant cupping. Leung et al.22
observed significant changes in ONH measurements when the reference plane was placed 55 μm above or below the default reference plane, indicating the variability of measurements if the reference plane was not stable. The ONH analysis software used for the present study made direct measurements of both the disc and the cup that depended only on the anatomy delineated rather than on a reference plane.
As can be seen in , on average some parameters measure larger differences between mild and moderate glaucoma than between moderate and severe glaucoma (for example, average, inferior, and nasal RNFL), while others (superior RNFL as well as rim area and CDR) manifest larger differences between moderate and severe glaucoma. The usefulness of a parameter for detecting progression depends on the relative size of these differences between stages compared with the TRT SD, the variability of parameter measurements occurring in the absence of true change. expresses the TRT SD as a percentage of these between-disease-stage differences, similar to a coefficient of variation. Smaller percentages indicate a higher likelihood of ability to detect a difference. Despite its subjective nature and intraobserver and interobserver variability when assessed with ophthalmoscopy and photography, CDR is still used as an indicator for glaucoma assessment. The finding that automated CDR calculation with the Cirrus HD-OCT ONH software was highly reproducible may have favorable clinical implications and holds promise for a longitudinal study of change.
Good reproducibility and low variability are required to accurately measure glaucoma progression. A consensus has yet to be reached on the average RNFL thinning limit over which glaucoma progression should be considered. However, based on the intervisit TRT SD for average RNFL thickness found in this study (), we estimated that intervisit thinning of at least 4 μm may be considered as suspicious and may result from glaucoma progression rather than from inconsistencies in the measurements because of other factors. This was similar to the 4.86-μm change recently suggested by Leung et al. 10
but was much lower than the 8.0-μm and 11.67-μm changes in studies conducted by Budenz et al.16
and Leung et al.,23
respectively, using Stratus OCT. The improved reproducibility of average RNFL thickness and even quadrant and clock hour measurements of RNFL are most likely the result of the improved method for measuring the scan circle with Cirrus HD-OCT compared with Stratus TD-OCT. Stratus TD-OCT requires the operator to manually place the scan circle, whereas Cirrus HD-OCT places the scan circle automatically without operator input. Although the operator may not place the scan cube in the same location each time with the Cirrus HD-OCT, the instrument will extract data from the same scan circle each time. These findings may have applications in longitudinal monitoring of glaucoma and other conditions characterized by progressive thinning of the peripapillary RNFL.
The results of this study must be interpreted by recognizing some limitations. First, only good quality scans with signal strength ≥6 were included in the analyses, which might have influenced the upper limit of the variability of our measurements. Therefore, the results reported herein may only be valid in patients with good quality scans, and caution should be exercised when diagnosing glaucoma progression based on series including both good and poor quality scans. It would be interesting to know how Cirrus HD-OCT performs when poor quality scans attributed to media opacities are taken into consideration, which likely represents the scenario in daily clinical practice. However, in our own clinical practice, we disregard the numbers for any scans with signal strength <6. In our experience, these patients are better monitored with other technologies. Second, some participants had experience with OCT technology testing, which might have contributed to the low variability of the observed measurements. Although this seems unlikely, confirmatory studies are needed. Third, despite that fact that we made an effort to include a wide range of glaucoma severities, our data may only pertain to the population we analyzed and may not be generalizable to all clinical situations.
In conclusion, both intravisit and intervisit measurements of peripapillary RNFL and ONH parameters obtained with Cirrus HD-OCT were found to have excellent reproducibility, indicating that this instrument may be useful in the longitudinal assessment of glaucoma progression.