Choroideremia

Overview

Choroideremia is an X-linked recessive chorioretinal dystrophy caused by mutations in the CHM gene encoding Rab escort protein-1 (REP-1). It is characterized by progressive degeneration of the choroid, retinal pigment epithelium (RPE), and photoreceptors. Affected males typically present with night blindness in childhood, followed by progressive peripheral field loss, and eventual central vision loss in middle age. Female carriers may show mild fundus changes but generally retain good vision.

Genetics

Choroideremia is caused exclusively by mutations in the CHM gene on chromosome Xq21.2. Over 250 pathogenic variants have been identified, including nonsense mutations, frameshift mutations, and large deletions.

Clinical Presentation

Diagnosis

• Fundus examination: Characteristic scalloped degeneration of choroid and RPE from periphery inward
• Fundus autofluorescence: Preserved central island surrounded by absent autofluorescence
• OCT: Preserved central photoreceptors with surrounding atrophy
• ERG: Reduced rod and cone responses
• Visual field: Peripheral constriction with preserved central island
• Genetic testing: CHM gene sequencing and deletion analysis

Current Research & Treatment

Choroideremia was one of the first IRDs to enter clinical trials for AAV-mediated gene therapy. AAV2-REP1 gene therapy (Nightstar/Biogen) demonstrated visual improvement in Phase 1/2 trials. Multiple Phase 2/3 trials are ongoing. The preserved central island of photoreceptors in choroideremia makes it an attractive target for gene therapy intervention before central vision is lost.

Active Clinical Trials

The following active clinical trials are investigating treatments for Choroideremia. Trial status and enrollment may change; always verify directly on ClinicalTrials.gov.

Supporting Organizations

The following nonprofit organizations fund research, support patients, and advocate for advances in the treatment and cure of Choroideremia.