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Original Investigation |

Quantification of Ellipsoid Zone Changes in Retinitis Pigmentosa Using en Face Spectral Domain–Optical Coherence Tomography

Amir H. Hariri, MD1,2; Hong Yang Zhang, MD1,2; Alexander Ho, BSE1; Peter Francis, MD3; Richard G. Weleber, MD4; David G. Birch, PhD5; Frederick L. Ferris III, MD6; SriniVas R. Sadda, MD1,2 ; for the Trial of Oral Valproic Acid for Retinitis Pigmentosa Group
[+] Author Affiliations
1Doheny Eye Institute, Los Angeles, California
2Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles
3Pacific Ophthalmology Consulting, Portland, Oregon
4Casey Eye Institute, Oregon Health & Science University, Portland
5Retina Foundation of the Southwest, Dallas, Texas
6Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland
JAMA Ophthalmol. 2016;134(6):628-635. doi:10.1001/jamaophthalmol.2016.0502.
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Published online

Importance  New methods are needed to quantify the change in the outer retinal structures in retinitis pigmentosa (RP).

Objective  To implement an alternate method for tracking ellipsoid zone (EZ) changes in RP by quantifying the EZ area on en face spectral domain–optical coherence tomographic (SD-OCT) images.

Design, Setting, and Participants  Data for this observational case study were collected at the Department of Ophthalmology, University of California, Los Angeles, from May 1 to July 30, 2015, and included SD-OCT images of a subset of patients from the Trial of Oral Valproic Acid for Retinitis Pigmentosa. To be eligible for the en face OCT subanalysis, the preserved EZ area was required to be limited to the SD-OCT scanning field. Cases in which the EZ band extended to the margins of any B-scan or the most superior or inferior B-scan were excluded. The SD-OCT images of all included cases were imported into the manufacturer’s software to generate en face images at the level of the EZ. Two certified SD-OCT graders independently delineated the boundaries of the preserved EZ on the en face images.

Main Outcomes and Measures  Comparison of the 2 masked gradings of the generated en face images of patients with RP for agreement between the graders and the validity of the method.

Results  Of the 43 available patients with volume SD-OCT data, 45 eyes of 24 patients met the eligibility criteria and were included in this subanalysis. Every patient had 2 visits that were 1 year apart, which included a total of 90 en face OCT images that were graded. The mean (SD) absolute difference and percentage difference between the 2 independent graders for each visit were 0.08 (0.10) mm2 and 4.5% (5.9%), respectively. The EZ area determined by the 2 graders showed excellent agreement with an intraclass correlation coefficient of 0.996 (95% CI, 0.995-0.997; P < .001).

Conclusions and Relevance  Quantification of the preserved EZ area on en face SD-OCT images of patients with RP is a valid and reproducible method. En face SD-OCT quantification may be a useful tool for monitoring the EZ changes of patients with advanced RP and a useful outcome measurement variable in therapeutic trials.

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Figures

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Figure 1.
Ellipsoid Zone (EZ) of an Ineligible Eye

A, The EZ is discernible in the uppermost B-scan (B-scan 97/97 on upper right) and the nasal end of B-scan 33/97 (lower right). B, In the resultant en face spectral domain–optical coherence tomographic image, the preserved EZ extends beyond the scanned area.

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Figure 2.
Generation of Graded En Face Spectral Domain–Optical Coherence Tomographic (SD-OCT) Image

A, Red lines on the B-scan illustrate the slab boundaries used to generate the en face SD-OCT image. B, En face SD-OCT image. C, Graded en face image using the “draw region” tool in the SD-OCT manufacturer’s software. The exact location of the drawn boundary on all corresponding B-scans is discernible (2 small vertical blue lines within the slab in part A).

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Figure 3.
Bland-Altman13 Plot of Intergrader Reproducibility

Comparison of the measurement of the ellipsoid zone (EZ) area on en face spectral domain–optical coherence tomographic images between the 2 graders is shown. The mean preserved EZ area is calculated from measurements by both graders. Data points indicate individual images (45 eyes).

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Figure 4.
Effect of the Size of the Preserved Ellipsoid Zone (EZ) Area on the Percentage Difference Between the Graders

Box and whisker plot illustrates the effect of the size of the preserved EZ area on the percentage difference between the 2 graders using the drawn boundary method. Horizontal lines indicate 25th, 50th, and 75th percentiles; boxes, amounts that are between 25th and 75th percentiles; whiskers connect 25th percentile and 75th percentile to minimum and maximum amount of preserved EZ within every group; and points beyond the whiskers, outliers.

aIndicates an extreme outlier that is 3 interquartile ranges above the 75th percentile of the box.

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Figure 5.
An Eye With a High Percentage Difference Between the Graders

The difference between the graders was 23%. A and B, The precise boundaries of the preserved ellipsoid zone (EZ) band are difficult to discern on the en face spectral domain–optical coherence tomographic (SD-OCT) image and regular B-scans. C and D, The individual gradings are illustrated side by side. One of the graders who measured the preserved EZ area as 2.81 mm2 was not very precise in the grading; the other grader who measured the area as 2.24 mm2 was more meticulous.

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