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. 2019 Jun:202:79-90.
doi: 10.1016/j.ajo.2019.02.007. Epub 2019 Feb 14.

Correlation of Outer Retinal Degeneration and Choriocapillaris Loss in Stargardt Disease Using En Face Optical Coherence Tomography and Optical Coherence Tomography Angiography

Talal Alabduljalil  1 , Rachel C Patel  2 , Abdullah A Alqahtani  3 , Simon S Gao  4 , Michael J Gale  2 , Miao Zhang  5 , Yali Jia  2 , David Huang  2 , Pei-Wen Chiang  2 , Rui Chen  6 , Jun Wang  6 , Richard G Weleber  2 , Mark E Pennesi  2 , Paul Yang  7
Affiliations

Correlation of Outer Retinal Degeneration and Choriocapillaris Loss in Stargardt Disease Using En Face Optical Coherence Tomography and Optical Coherence Tomography Angiography

Talal Alabduljalil et al. Am J Ophthalmol. 2019 Jun.

Abstract

Purpose: This study measured and correlated degeneration of the junction between the inner and outer segments (IS/OS), the retinal pigment epithelium (RPE), and the choriocapillaris (CC) in Stargardt disease (STGD).

Design: Prospective cross-sectional study.

Methods: This study was conducted at the Casey Eye Institute. A total of 23 patients with STGD were enrolled and underwent optical coherence tomography angiography (OCTA). Scans were centered on the fovea. OCT slab projections and en face boundary maps were used to create masks to measure total IS/OS loss or RPE atrophy as well as regions of isolated IS/OS loss, isolated RPE atrophy, and matched IS/OS and RPE degeneration or intact IS/OS junction and RPE. CC vascular density (CCVD) was quantified from the CC angiogram. Outcomes included the area of loss, and the CCVD of degeneration in different areas was quantified and correlated.

Results: The total area of IS/OS loss was strongly correlated with the total area of RPE atrophy (r = 0.96; P < 0.0001) by a 1.6:1 ratio (r2 = 0.90). CCVD within regions of matched degeneration (85.6% ± 2.7%; P < 0.0001), isolated IS/OS junction loss (93.6% ± 1.0%; P = 0.0011), and isolated RPE atrophy (94.1% ± 1.1%; P = 0.0065) were all significantly lower than normal (99.0% ± 0.17%). There was a trend for CCVD within intact areas (97.6% ± 0.38%) to decline as the area diminished (r = 0.68).

Conclusions: Photoreceptor and RPE degeneration exhibited a strong relationship wherein the IS/OS loss was 1.6-fold greater than that of RPE atrophy, supporting the theory that photoreceptor degeneration precedes RPE in STGD. Both the photoreceptors and the RPE degeneration contributed synergistically to CCVD attenuation, but extralesional CCVD also tended to be abnormal. The findings and techniques in this study may be of utility in developing endpoints for clinical trials.

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Figures

Figure 1:
Figure 1:. Methods for en face slab projection, boundary maps, and mask analysis
Sample images from patient 2 showing one b-scan with preserved IS/OS and RPE and another with only isolated RPE atrophy (a). Slab position (blue line) is optimized manually for both IS/OS and RPE layer, utilizing autofluorescence images as reference for the later (b). The en face projections of the IS/OS and RPE slab is shown along with the boundary lines (cyan) of IS/OS and RPE atrophy, respectively, from one grader (c, d). The IS/OS loss mask (dark yellow) and RPE atrophy mask (dark cyan) are created from the boundary maps (e), then overlaid to create the IS/OS-RPE composite mask (f). The composite mask identifies four types of regions of degeneration, which are used for the analysis of area (g) and CCVD (h). IS/OS, inner segment/outer segment layer; RPE, retinal pigment epithelial layer; OCTA, OCT angiography; CCVD, choriocapillaris vessel density.
Figure 2:
Figure 2:. Age vs. BCVA, and total RPE atrophy vs. total IS/OS loss
(Top) Scatter plot of age vs. BCVA, which shows no correlation. (Middle) On average, total IS/OS loss tended to be greater than total RPE atrophy, however it was not statistically significant and the data was skewed by floor effect of complete loss of layers (36 mm2) in 6 patients for IS/OS loss and 3 patients for RPE atrophy. (Bottom) Scatter plot of total RPE atrophy vs. IS/OS atrophy shows a strong correlation, excluding data points that suffer from floor effect (red circles). For reference, the dotted line represents a 1:1 relationship. BCVA, best-corrected visual acuity; IS/OS, inner segment/outer segment layer; RPE, retinal pigment epithelial layer
Figure 3:
Figure 3:. Composite mask analysis of area of loss
(Top) Samples images of composite analysis, which is color-coded to show the four different patterns of degeneration: areas of no degeneration (white), matched degeneration (black), isolated IS/OS loss (gray), and isolated RPE atrophy (red). Patients 2, 19, and 11 show large areas of matched degeneration and isolated IS/OS loss, while patients 3, 10, and 14 show diffusely intact IS/OS and RPE with central area of mixed types of degeneration. Both patient 2 and 14 show foveal preservation of IS/OS and RPE. Overall, isolated RPE atrophy was not common. (Bottom left) On average, the area of matched degeneration was similar to the area of mismatched degeneration (isolated IS/OS loss + isolated RPE atrophy). (Bottom right) The area of isolated IS/OS loss was significantly greater than the area of isolated RPE atrophy. IS/OS, inner segment/outer segment layer; RPE, retinal pigment epithelial layer; Asterisk, p =0.0005.
Figure 4:
Figure 4:. Correlation analysis of region types of degeneration
(Left top and bottom) Scatter plots of isolated IS/OS loss vs. matched or mismatched degeneration show a strong correlation. (Right top and bottom) Scatter plots of isolated RPE atrophy vs. matched or mismatched degeneration show no correlation. Data points with floor effect (red) were excluded from analysis. IS/OS, inner segment/outer segment layer; RPE, retinal pigment epithelial layer.
Figure 5:
Figure 5:. Age or BCVA vs. CCVD, and composite mask analysis of CCVD
(Top and middle) Scatter plot of age or BCVA vs. CCVD show a moderate correlation of declining CCVD with increasing age or decreasing BCVA (increasing logMAR), however statistical significance was limited by multiple comparisons (see table 2). (Bottom) Total CCVD from normal subjects were significantly greater than total CCVD and the CCVD within the various region types of degeneration in Stargardt patients, except for areas of intact IS/OS and RPE. The CCVD within intact areas were significantly greater than the CCVD within areas of matched degeneration in Stargardt patients. Solid line with error bar represents mean and 95% confidence interval. BCVA, best-corrected visual acuity; IS/OS, inner segment/outer segment layer; RPE, retinal pigment epithelial layer; OCTA, OCT angiography; CCVD, choriocapillaris vessel density; Asterisk, p ≤0.05.
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