The Dark-Adapted Retinal Function Response in Choroideremia (DARC) Study

Duke University

Overview

Choroideremia (CHM) is an inherited retinal disorder that causes progressive vision loss, ultimately leading to complete blindness. The first symptom is generally night blindness, although, to date, little is known about the extent, type, pattern, and progression of dark-adapted visual function measures in CHM patients. We hypothesize that one of the key events causing night blindness in CHM is deficiency in the chromophore of the rod visual pigment, rhodopsin. We propose that this deficiency is at least in part due to inadequate delivery of vitamin A (all-trans-retinol) to the photoreceptors (PRs) from the ailing retinal pigment epithelium (RPE), characteristic of CHM. We hypothesize that increased availability of vitamin A would potentiate its entry into the RPE-mediated visual cycle, ultimately enabling delivery to the PRs. This would in turn allow rods to perform better by partially overcoming the RPE damage and the impaired chromophore recycling that we postulate exists in CHM. The goals of this proposal are: (1) to test the hypothesis that oral vitamin A supplementation can improve night time and peripheral vision in CHM patients, and (2) to provide detailed characterization of dark-adapted visual function outcome measures to guide interventional CHM trials.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Conditions

Choroideremia

Interventions

Outcomes

Primary Outcomes

Change in dark-adapted full-field visual field sensitivity

Dark-adapted full-field visual field sensitivity will be measured using the Medmont dark-adapted chromatic perimeter.

Time frame: Measurements at 0, 4, and 8 months. The 0 months measurement will serve as the baseline. The 4 month measurement will assess change due to vitamin A supplementation. The 8 month measurement will assess reversal of this change following washout period

Change in dark-adapted macular visual field sensitivity

Dark-adapted macular visual field sensitivity will be measured using the Medmont dark-adapted chromatic perimeter.

Change in dark adaptometry

Dark adaptometry will be measured using the MacuLogix AdaptDx dark adaptometer.

Secondary Outcomes

Change in best corrected visual acuity

Best corrected visual acuity will be measured using the ETDRS chart

Change in low luminance visual acuity

Low luminance visual acuity will be measured using the ETDRS chart in low luminance conditions

Change in full-field light-adapted visual field sensitivity

Light-adapted full-field visual field sensitivity will be measured using the Octopus 172-point GATE full-field semi-automated kinetic perimetry (SKP)

Change in light-adapted macular visual field sensitivity

Light-adapted macular visual field sensitivity will be measured using the Centervue MAIA confocal macular microperimeter

Change in retinal pigmented epithelium (RPE) atrophy by optical coherence tomography

Retinal pigmented epithelium (RPE) atrophy will be measured using the Spectralis macular spectral domain optical coherence tomography (SD-OCT) with and without enhanced depth imaging (EDI)

Change in retinal pigmented epithelium (RPE) atrophy by color photography

Retinal pigmented epithelium (RPE) atrophy will be measured using the Optos wide-field color fundus photography (WF-CFP)

Change in retinal pigmented epithelium (RPE) atrophy by fundus autofluorescence

Retinal pigmented epithelium (RPE) atrophy will be measured using the Optos wide-field fundus auto-fluorescence (WF-FAF)

Change in retinal pigmented epithelium (RPE) atrophy by fundoscopy

Retinal pigmented epithelium (RPE) atrophy will be assessed by slit lamp biomicroscopy

Change in liver function

Liver function profile will be measured by laboratory using participant serum samples

Time frame: Measurements at 0, 4, and 8 months

Change in serum vitamin A levels

Serum vitamin A levels will be measured by laboratory using participant serum samples