Prospective deep phenotyping of choroideremia patients using multimodal structure-function approaches

Abstract

Objective To investigate the retinal changes in choroideremia (CHM) patients to determine correlations between age, structure and function. Subjects/Methods Twenty-six eyes from 13 male CHM patients were included in this prospective longitudinal study. Participants were divided into <50-year (n = 8) and ≥50-year (n = 5) old groups. Patients were seen at baseline, 6-month, and 1-year visits. Optical coherence tomography (OCT), OCT angiography, and fundus autofluorescence were performed to measure central foveal (CFT) and subfoveal choroidal thickness (SCT), as well as areas of preserved choriocapillaris (CC), ellipsoid zone (EZ), and autofluorescence (PAF). Patients also underwent functional investigations including visual acuity (VA), contrast sensitivity (CS), colour testing, microperimetry, dark adaptometry, and handheld electroretinogram (ERG). Vision-related quality-of-life was assessed by using the NEI-VFQ-25 questionnaire. Results Over the 1-year follow-up period, progressive loss was detected in SCT, EZ, CC, PAF, and CFT. Those ≥50-years exhibited more structural and functional defects with SCT, EZ, CC, and PAF showing strong correlation with patient age (rho ≤ −0.47, p ≤ 0.02). CS and VA did not change over the year, but CS was significantly correlated with age (rho = −0.63, p = 0.001). Delayed to unmeasurable dark adaptation, decreased colour discrimination and no detectable ERG activity were observed in all patients. Minimal functional deterioration was observed over one year with a general trend of slower progression in the ≥50-years group. Conclusions Quantitative structural parameters including SCT, CC, EZ, and PAF are most useful for disease monitoring in CHM. Extended follow-up studies are required to determine longitudinal functional changes.

Genetic defects of CHM and visual acuity outcome in 24 choroideremia patients from 16 Japanese families

“…Similar results have been previously described in CHM patients 12,32 . Previous studies of FAF analysis have revealed that a significant negative correlation is observed between age and the area of PAF 23,31,33 . The PAF area of patient 10 at 52 years old was smaller than that of patient 14 at 27 years old and patient 22 at 16 years old (Fig.…”

“…An OCT study of 61 eyes from 39 CHM patients has revealed that the central retinal thickness was within normal limits until the 40 s, followed by significant thinning between 40 and 60 years of age 30 . Another study of 26 eyes from 13 CHM patients has demonstrated that no association was detected between CFT and age 31 . Our results also showed no correlation between the CFT and age (Fig.…”

Update on Gene Therapy Clinical Trials for Choroideremia and Potential Experimental Therapies

“…In order to investigate these retinal changes, several structural and functional tests have been used [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. Fundus autofluorescence (FAF) can monitor the progressive concentric loss of autofluorescence, retaining a residual retinal island at the macula of preserved autofluorescence (PAF) [ 21 ].…”

“…The rate of FAF loss was estimated to be 7.7% per year [ 21 ]. Areas of PAF have been reported to be vertically expanded and favoring the central and the temporal side of the macula [ 20 ]. Spectral domain optical coherence tomography (SD-OCT) reveals attenuation of the ellipsoid zone, [ 18 , 22 ] reduction of outer nuclear layer thickness [ 22 ], and outer retinal tubulations due to primary RPE dysfunction [ 18 , 23 ].…”

“…In CHM adults, macular cystic edema was also identified [ 11 , 18 , 27 ] and correlated with progressive decrease in VA and poor prognostic outcomes [ 18 ]. OCT angiography (OCTA) [ 24 , 28 ] has shown the ability to detect vascular changes in retinal and choroidal circulations noninvasively in CHM, highlighting decreased vascular density [ 17 , 19 ] that precedes photoreceptor loss [ 20 ]. Confocal adaptive optics scanning light ophthalmoscopy (AOSLO) is able to provide effective photoreceptor cellular structure characterization [ 23 , 25 ].…”