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 RELEVANCEThe 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.

Inner segment ellipsoid band length is a prognostic factor in retinitis pigmentosa associated with EYS mutations: 5-year observation of retinal structure

“…Although a change in the retinal structure of RP patients with the same genetic mutations over the medium term (2 years) has been reported, 12,13 no study, to our knowledge, has investigated the changes over the longer term (5 years). Because the change of retinal structure is gradual, it is necessary to assess the change using a long-term follow-up data.…”

Outer Segment Thickness Predicts Visual Field Response to QLT091001 in Patients withRPE65orLRATMutations

“…It is well established that OS thickness is related to traditional measures of visual function in RP, such as multifocal electroretinogram, full-field electroretinograms, and visual field sensitivity. [16][17][18][19][20] However, it is unknown whether OS thickness of a study patient at baseline could be used as a predictor for the Goldmann visual field (GVF) response to QLT091001 or whether GVF treatment response is also related to increase in OS thickness. Therefore, we examined the relationship between macular photoreceptor OS thickness measured by SD-OCT and measurement of GVF improvement from baseline after treatment with QLT091001.…”

Outer Retinal Changes Including the Ellipsoid Zone Band in Usher Syndrome 1B due toMYO7AMutations

“…21 In the current work we will use the term ''EZ extent'' to refer to the distance between the fovea and the location ''EZ edge'' where the EZ band becomes indistinguishable from the RPE along both the horizontal and vertical meridians. Previously used ''EZ width'' 9 would be approximately twice the EZ extent used here assuming symmetry around the fovea. Scans with an indistinguishable EZ band were excluded.…”

“…[6][7][8] Very recently, evidence has been put forth that a specific OCT feature of the photoreceptor laminae, the inner/outer segment border or ellipsoid zone (EZ), is able to be used to reliably determine the natural history of photoreceptor progression in Xlinked retinitis pigmentosa (XLRP). 9,10 This is a major step forward, considering the need for such parameters in current and future clinical trials of IRDs. Beyond natural histories of IRDs, there is the hope that such objective markers will also be potential outcome measures and permit decisions over a relatively short term about safety and efficacy of therapies.…”

“…9,11,12 Many future trials, however, are not being designed only to treat the central retina in which the EZ extent may be readily measurable. If there is intent to evaluate and treat more than the central retina or even to exclude treatment of the central retina, does EZ extent remain the marker to quantify, independent of retinal location and disease type?…”