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Brandon J Lujan, Emily Y Chew, Jacque L Duncan, Bhavna J Antony, Vikram Makhijani, Austin Roorda; Altered Photoreceptor Bands Surrounding Areas of Loss in MacTel Cause En Face OCT Endpoint Variability. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4250.
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© ARVO (1962-2015); The Authors (2016-present)
A phase II clinical trial of macular telangiectasia type 2 (MacTel) is currently underway using the area of photoreceptor ellipsoid zone (EZ) loss on en face optical coherence tomography (OCT) as the primary outcome measure. We sought to determine if the pupil position through which OCT data is acquired causes variability in this measurement.
We analyzed Cirrus OCT data of 6 eyes of 3 patients with MacTel who were not enrolled in the clinical trial. Directional OCT (D-OCT) was utilized to acquire on-axis and off-axis volumetric and cross-sectional datasets. En face slabs were generated through the EZ, and areas of apparent photoreceptor loss were manually segmented and measured. Cross-sectional D-OCT hybrid images were generated to assess alterations in the directional reflectivity of the EZ and interdigitation zone (IZ) bands.
En face OCT imaging of each MacTel eye demonstrated areas of photoreceptor loss, defined by a marked decrease in the reflectivity of photoreceptor slabs compared to the surrounding unaffected area. On-axis en face OCT imaging showed reproducibly smaller areas of photoreceptor loss compared to off-axis scans due to this reflectivity change. The mean (SD) mm2 area of on-axis photoreceptor loss in all eyes was 1.28 (0.66) compared to mean off-axis area of 1.79 (0.82). The mean (SD) on-axis area was 69% (17%) smaller than the mean off-axis area, paired t-test p=0.01. Cross-sectional D-OCT hybrid images revealed flanking zones of altered EZ and IZ bands in 6/6 eyes, indicating uniform but misdirected photoreceptor orientation.
The ability to accurately measure the area of photoreceptor loss on en face OCT is central to quantifying the progression of MacTel. However, significantly different measurements can by obtained by altering the pupil entry position of the OCT beam. This variability is a consequence of the way OCT data are acquired, and is independent of the specific OCT system or image analysis method used. For the primary outcome measure of MacTel studies, standardization of pupil entry position during scan acquisition should be implemented to ensure accurate and precise metrics of progression. For exploratory outcome measures, the change in directional reflectivity of the surrounding photoreceptors may reveal new pathophysiological properties of MacTel, and should be investigated as a potential biomarker of disease progression.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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