Cone Structure Persists Beyond Margins of Short-Wavelength Autofluorescence in Choroideremia

Abstract

Citation: Foote KG, Rinella N, Tang J, et al. Cone structure persists beyond margins of short-wavelength autofluorescence in choroideremia. Invest Ophthalmol Vis Sci. 2019;60:4931-4942. https://doi.org/10.1167/ iovs.19-27979 PURPOSE. We studied the relationship between structure and function of the choriocapillaris (CC), retinal pigment epithelium (RPE), and photoreceptors in patients with choroideremia (CHM). METHODS.Six CHM patients (12 eyes) and four normal subjects (six eyes) were studied with fundus-guided microperimetry, confocal and nonconfocal adaptive optics scanning laser ophthalmoscopy (AOSLO), near-infrared and color fundus photos, short wavelength fundus autofluorescence (SW-AF), and swept-source optical coherence tomography (SS-OCT) and angiography (SS-OCTA) images. Cone spacing was represented using Z-scores (standard deviations from the mean at that eccentricity). CC flow voids were defined using a threshold of 1 SD below the normal mean. RESULTS.Cone spacing Z-scores were not significantly correlated with distance from the borders of preserved RPE, determined using either the SS-OCT or SW-AF scans. Cone spacing Z-scores were significantly correlated with CC flow voids and retinal sensitivity. Flow voids were abnormal in regions of preserved RPE and increased progressively from within À28 of the preserved area to þ28 beyond the border. Visual sensitivity decreased as CC flow voids increased approaching and beyond the border of preserved structure. CONCLUSIONS.In CHM, cone spacing Z-scores correlated with CC flow voids, and were negatively correlated with retinal sensitivity, suggesting cone degeneration accompanied reduced CC perfusion. Functional cones were found outside the presumed borders of preserved outer-retina/RPE as defined by SW-AF, but not outside the borders determined by SS-OCT. The use of SW-AF to identify the border of preserved structures may underestimate regions with cells that may be amenable to treatment.

Comparing Fluorescence Lifetime Imaging Ophthalmoscopy in Atrophic Areas of Retinal Diseases

“… 51 According to the authors, this could indicate preserved metabolic activity in the photoreceptors. Pfau and colleagues 52 found preserved light sensitivity in border regions within the atrophic areas of GA, whereas Foote and colleagues 53 demonstrated similar results in patients affected by choroideremia. The border regions within atrophic areas of GA and choroideremia also show short FLIO lifetimes, as has been shown in previous FLIO studies.…”

Role of LINC01592 in TGF-β1-induced epithelial-mesenchymal transition of retinal pigment epithelial cells

“…Epithelial-mesenchymal transformation (EMT) plays an indispensable role in oxidative stress, stem cell differentiation, growth, and wound healing, but also promotes the occurrence and development of cell fibrosis and cancer pathologies [ 5 , 6 ]. Previous studies confirmed that EMT of RPE cells mediated by transforming growth factor beta 1 (TGF-β1) is the main reason for pathological changes associated with PVR [ 7 , 8 ]. RPE cells convert from an epithelial to mesenchymal phenotype and participate in EMT [ 9 , 10 ].…”

Widespread subclinical cellular changes revealed across a neural-epithelial-vascular complex in choroideremia using adaptive optics

“…The name of the disease suggests primary involvement of the choroid 5 , a vascularized support structure for the outer retina. For example, choriocapillaris degeneration has been linked with declining visual function in choroideremia 6 . However, several studies have suggested that choroideremia primarily affects the retinal pigment epithelial (RPE) cells 7 – 11 .…”

“…Adaptive optics (AO) retinal imaging 31 has provided cellular-level resolution of the living human retina in patients with choroideremia, particularly for assessing the status of cone photoreceptors 6 , 9 , 32 , 33 . Structurally, well-preserved cone photoreceptors have been reported at the margins of RPE atrophy 16 , 33 but areas of reduced cone density elsewhere have also been observed 9 , 16 , 32 .…”