Structural retinal and visual cortex phenotyping and gene therapy in achromatopsia
type: CreativeWork
description: Achromatopsia (ACHM) is a rare inherited retinal disorder affecting cone photoreceptor function. Patients with ACHM display reduced visual acuity, colour vision deficiency, photoaversion and nystagmus as core features of this disease. Variants in two genes, CNGA3 and CNGB3 are responsible for 70% of reported cases. Patient management currently centres on visual impairment certification, symptom alleviation and adaptation, with no curative options available. The last decade has seen significant progress in gene therapy for other ophthalmic conditions such as RPE65- associated Lebers Congenital Amaurosis (LCA), with several trials now targeting ACHM. In this thesis I investigate retinal and primary visual cortex structural changes in ACHM to assess their ability to provide novel trial endpoints or inform potential treatment windows. I undertook the first longitudinal assessment of the foveal cone mosaic in CNGA3 associated ACHM utilising adaptive optics scanning laser ophthalmoscopy (AOSLO). The results support the non-progressive nature of ACHM and the potentially large therapeutic window available, but also describe the difficulty of applying this imaging modality to paediatric patients in clinical trials. Structural changes in both the cortical thickness and surface area of the primary visual cortex have been shown to occur in a multitude of pathologies resulting in early onset blindness. I undertook a study to examine, through MRI, these changes in the youngest ACHM cohort to date and whether they correlate with foveal morphology assessed by optical coherence tomography (OCT). The results corroborate the findings previously reported in older ACHM cohorts and show that cortical structural changes occur early on and are specific to the foveal representation in the primary visual cortex; the area of retina affected in ACHM due to the cone photoreceptor dominance in this retinal region. This suggests early intervention may be necessary as previous studies have suggest…
abstract: Achromatopsia (ACHM) is a rare inherited retinal disorder affecting cone photoreceptor function. Patients with ACHM display reduced visual acuity, colour vision deficiency, photoaversion and nystagmus as core features of this disease. Variants in two genes, CNGA3 and CNGB3 are responsible for 70% of reported cases. Patient management currently centres on visual impairment certification, symptom alleviation and adaptation, with no curative options available. The last decade has seen significant progress in gene therapy for other ophthalmic conditions such as RPE65- associated Lebers Congenital Amaurosis (LCA), with several trials now targeting ACHM. In this thesis I investigate retinal and primary visual cortex structural changes in ACHM to assess their ability to provide novel trial endpoints or inform potential treatment windows. I undertook the first longitudinal assessment of the foveal cone mosaic in CNGA3 associated ACHM utilising adaptive optics scanning laser ophthalmoscopy (AOSLO). The results support the non-progressive nature of ACHM and the potentially large therapeutic window available, but also describe the difficulty of applying this imaging modality to paediatric patients in clinical trials. Structural changes in both the cortical thickness and surface area of the primary visual cortex have been shown to occur in a multitude of pathologies resulting in early onset blindness. I undertook a study to examine, through MRI, these changes in the youngest ACHM cohort to date and whether they correlate with foveal morphology assessed by optical coherence tomography (OCT). The results corroborate the findings previously reported in older ACHM cohorts and show that cortical structural changes occur early on and are specific to the foveal representation in the primary visual cortex; the area of retina affected in ACHM due to the cone photoreceptor dominance in this retinal region. This suggests early intervention may be necessary as previous studies have suggest…
author: Katta, Mohamed Mousbah
keywords: Achromatopsia, ACHM
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/b64af389-b4e1-4c4f-a5e8-428493fb624b/download
license: http://purl.org/NET/rdflicense/allrightsreserved/
date published: 2024-05
date modified: 2026-07-22T22:24:16Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.116319