Spectral-domain optical coherence tomography measures of outer segment layer progression in patients with X-linked retinitis pigmentosa

Abstract

Importance: Determining the annual rate of change in the width of the inner segment ellipsoid zone (EZ; ie, inner/outer segment border) in the context of short-term variability should allow us to better understand the value of this measure for future treatment trials in X-linked retinitis pigmentosa (XLRP).

Objectives: To identify the width of the central region showing an EZ and to determine the short-term repeat variability and the annual rate of change in the width of the EZ from spectral-domain optical coherence tomography (SD-OCT) measures in RP.

Design: Patients with recessive or simplex RP (age range, 8-65 years; mean age, 40.5 years) underwent scanning twice on the same day to evaluate test-retest variability. Patients with XLRP (age range, 8-27 years; mean age, 15.2 years) from a larger group participating in an ongoing double-blind treatment trial (docosahexaenoic acid vs placebo; clinicaltrials.gov NCT00100230) underwent spectral-domain optical coherence tomography line scanning across the horizontal meridian at 3 yearly intervals.

Setting: Research center specializing in medical retina.

Participants: Forty-eight patients with RP, including 20 with recessive or simplex RP and 28 with XLRP, and 23 healthy control subjects.

Main outcome and measure: Widths of the EZ calculated and compared among the 3 annual visits.

Results: Test-retest differences were normally distributed, and the magnitude of the difference was independent of mean EZ width. The mean (SD) for test-retest differences in EZ width was 0.08° (0.22°) (range, -0.30° to 0.60°). Thus, 95% of all test-retest differences fall within ± 0.43° (124 μm). Of the 28 patients with XLRP, 27 showed a significant decrease in EZ width after 2 years. Patients with XLRP showed a mean annual decrease in EZ width of 0.86° (248 μm, or 7%).

Conclusions and relevance: The mean rate of decline in EZ width (7%) translates into a mean rate of change of 13% for the equivalent area of functioning retina. This rate of change is consistent with that reported for visual fields and full-field electroretinograms. Unlike visual fields and electroretinograms, however, the repeat variability is less than the annual rate of change. These results support the validity of EZ width as an outcome measure in prospective clinical trials in RP.

Figure 1

Spectral-Domain Optical Coherence Tomography Scan of the Horizontal Midline in a Patient With X-Linked Retinitis Pigmentosa Segmentation lines for the inner segment ellipsoid zone (EZ; inner/outer segment border) line band, the outer segment–retinal pigment epithelium (OS-RPE) junction, and the Bruch membrane (BM)–choroid junction are superimposed on the scan. The OS thickness relative to the normal mean EZ (2 SDs) for 23 healthy subjects is shown below. Vertical dashed lines indicate the retinal eccentricities at which OS thickness drops to 0 (ie, EZ becomes indistinguishable from the RPE).

Figure 2

Spectral-Domain Optical Coherence Tomography Scans of the Horizontal Midline From a Patient With Autosomal Recessive Retinitis Pigmentosa Undergoing Scanning Twice on the Same Day A and B, Magnified views of the transition zone are shown to the right. The first and second scans differed in inner segment ellipsoid zone (inner/outer segment border) width by 0.3° (86 µm).

Figure 3

Test-Retest Measures From 3 Patients With Autosomal Recessive Retinitis Pigmentosa Exhibiting a Range of Inner Segment Ellipsoid Zone (EZ; Inner/Outer Segment Border) Widths Thickness of the outer segment plus retinal pigment epithelium (OS + RPE) on scans 1 and 2 and thickness of the RPE on scans 1 and 2 when it is distinguishable from the EZ band are depicted. Vertical dashed lines indicate the horizontal extent of the EZ band. Solid and broken black lines indicate mean EZ thickness of 2 SDs for 23 healthy subjects.

Figure 4

Test-Retest Differences A, Test-retest differences were normally distributed with a mean of 0.08° (solid curve shows fit of Shapiro-Wilk normality test to distribution of widths [n = 20]). EZ indicates inner segment ellipsoid zone (inner/outer segment border). B, The magnitude of the test-retest difference for EZ was independent of the mean EZ width.

Figure 5

Representative Scans From a Patient With X-Linked Retinitis Pigmentosa Across 3 Annual Visits At the right is shown the inset at higher magnification. Arrows indicate the nasal edge of the inner segment ellipsoid zone (EZ; inner/outer segment border) each year. We detected a progressive shift in the remaining EZ band toward the center during the 3 annual visits.

Figure 6

Annual Measures From 3 Patients With X-Linked Retinitis Pigmentosa These 3 patients demonstrate the range of annual loss in inner segment ellipsoid zone (EZ; inner/outer segment border) width. Outer segment plus retinal pigment epithelium (OS + RPE) thickness on the first (visit A) and third (visit C) annual visits and thickness of the RPE when it is distinguishable from the EZ line on visits A and C are depicted. Vertical dashed lines indicate the horizontal extent of the EZ line. Solid and broken black lines indicate mean EZ thickness (2 SD) for 23 healthy subjects. A, This patient had a small decrease in EZ after 2 years. B, The second patient demonstrated average progression. C, The third patient demonstrated fast progression.

Figure 7

Relationship Between the Magnitude of Inner Segment Ellipsoid Zone (EZ; Inner/Outer Segment Border) Loss During 2 Years and Initial Width of EZ We detected a weak tendency for the magnitude of EZ loss to decrease in proportion to the initial EZ diameter (r² = 0.16[P = .03]).