Measurement bias between optical coherence tomography instruments can affect access to treatment: a new lottery

Dear editor

It is with great interest that we read the publication entitled “Critical appraisal of ranibizumab in the treatment of diabetic macular edema” by Stewart.¹ The author emphasized the importance of the vascular endothelial growth factor (VEGF) in the pathophysiology of diabetic macular edema (DME). As highlighted in that article, the anti-VEGF ranibizumab is a superior treatment compared to traditional argon photocoagulation, leading to better anatomical and functional results.

In April 2013, the National Institute for Health and Care Excellence (NICE) of the UK approved the use of ranibizumab as a treatment option to treat diabetic macular edema of the eye if it has a central macular thickness (CMT) of 400 μm or more at the beginning of the treatment.² The guidelines did not specify which optical coherence tomography (OCT) device(s) should be used for this assessment. This is important as, although good consistency has been shown in using the same instrument, there is a known divergence in CMT measurements between different instruments.^3–6 For example, the Spectralis® OCT (Heidelberg Engineering; Carsbad, CA, USA) generally shows higher values of mean CMT in a normal eye compared to most other instruments, in part due to the retinal segmentation algorithm that it employs.⁴ We hypothesized that similar (or increased) differences might be observed in DME, and that for those countries (such as the UK) where a fixed CMT is used to define eligibility for treatment, the “lottery” of OCT instruments may influence eligibility.

In light of this hypothesis, we conducted a preliminary analysis of 24 patients (48 eyes) with suspected DME who had OCT scans performed on the same day using both 3D OCT-1000 (Topcon; Itabashi, Tokyo, Japan) and Spectralis OCT. Matched macular-centered scans were obtained in 42 eyes; scans were not possible in 6 eyes due to media opacity or problems with patient fixation. The mean (standard deviation) CMT in this cohort was 282.0 (89.0) μm with a range of 191–689 μm using the Topcon OCT, and 312.4 (88.8) μm with a range of 224–719 μm using the Spectralis OCT (Figure 1A). Comparing the two instruments in our cohort using a Bland–Altman analysis, there was a bias of +10.73 μm to the Spectralis with a standard deviation of 10.32, and 95% limits of agreement of −9.497 to 30.96 μm (Figure 1B).

Figure 1.

Comparison of CMT measurements acquired on Topcon 3D OCT-1000 versus Spectralis® OCT for patients with DME. Direct comparison (A) and Bland– Altman plot (B).

Notes: Spectralis® OCT manufactured by Heidelberg Engineering (Carsbad, CA, USA); 3D OCT-1000 manufactured by Topcon (Itabashi, Tokyo, Japan).

Abbreviations: CMT, central macular thickness; DME, diabetic macular edema; OCT, optical coherence tomography.

Recognizing this issue is important for all those involved in care of patients in countries or institutions where the entry to treatment is limited by a defined CMT level. In the specific example considered here, this finding has a direct clinical impact on patients who have DME with a central macular thickness of 390–410 μm. In our small cohort of matched scans from 42 eyes, there were three whose CMT was >400 μm on the Topcon and four whose CMT was >400 μm on the Spectralis: ie, even in this small study, a patient’s eligibility for treatment depended on which scan was used. “Real-world” studies of OCT will become increasingly important if defined CMT levels are to be used as the “gate-keeper” for treatment, and should include repeatability and inter-instrument variability in defined patient cohorts.