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Kanmin Xue, Marta Oldani, Jasleen Jolly, Thomas L Edwards, Robert Maclaren; RPE degeneration precedes photoreceptor and choroidal loss in choroideremia based on enhanced-depth OCT and fundus autofluorescence correlations. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Choroideremia is an X-linked retinal dystrophy characterised by progressive centripetal degeneration of the outer retina, retinal pigment epithelium (RPE) and choriocapillaris. Determining the site of primary cell loss is vital for targeting potential gene or cell replacement therapy.
We conducted a retrospective observational analysis of enhanced-depth optical coherence tomography (EDI-OCT) and fundus autofluorescence (AF) imaging in 38 patients (76 eyes) with choroideremia. The edges of surviving outer retina on OCT and residual autofluorescence were aligned. The distribution of outer retinal tubulations was mapped over a range of ages (16-71 years), and comparison made between pre- and post-subretinal gene therapy. Subfoveal choroidal thickness (SFCT) was measured in 23 choroideremia patients (42 eyes) at different stages of outer retinal degeneration, and compared against 20 age- and refraction-matched male controls (40 eyes).
The edges of RPE autofluorescence aligned with a reduction in outer nuclear layer thickness (Spearman’s rho=0.9992). Correlation was also found between the quality of autofluorescence and integrity of ellipsoid zone within islands of surviving retina. Tubulations existed in 69 of 76 (91%) eyes with choroideremia and appeared to represent rearrangements of surviving photoreceptors following loss of their underlying RPE. These tubular structures remained stable following iatrogenic retinal detachment. SFCT was reduced at baseline in choroideremia (179.7±17.2 μm) compared with controls (302.0±4.8 μm) (P<0.0001), but did not undergo significant thinning until end-stage outer retinal loss (43.1±6.5 μm).
The data suggest that RPE loss precedes photoreceptor degeneration in choroideremia. The choroid is thinner than controls from early stages, in keeping with a mild developmental defect, but does not undergo further degeneration until end-stage outer retinal degeneration. Photoreceptors appear to lose outer segments following loss of underlying RPE but survive for an extended period by forming tubulations at the advancing edge of degeneration. The preservation of tubulations post-subretinal injection would be consistent with these structures maintaining attachment to the inner retina and hence being potentially amenable to therapeutic rescue.
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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