Purchase this article with an account.
Abigail T. Fahim, Sarwar Zahid, Kari Branham, Naheed Khan, Susanne Kohl, Bernd Wissinger, K T. Jayasundera, John R. Heckenlively; Progressive Foveal Outer Retinal Degeneration and a Therapeutic Window for Gene Therapy in Achromatopsia. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4553.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To describe the clinical phenotype and progressive foveal outer retinal degeneration in 7 patients with CNGA3 mutations and 7 patients with CNGB3 mutations.
A retrospective study was conducted of patients with two mutations in either CNGA3 or CNGB3. Clinical data examined included visual acuity, fundus photos, Goldmann visual fields (GVF), optical coherence tomography (OCT), and full-field electroretinography (ffERG). All patients had at least one OCT image, with longitudinal OCT data available for one patient.
Our patients ranged in age at first visit from 4 to 58 years. Visual acuities ranged from 20/80 to 20/400 for CNGA3 and 20/60 to 20/400 for CNGB3. ERG data were available for 13 patients. Four CNGA3 patients and one CNGB3 patient had non-recordable (NR) photopic b-waves. Eight patients had a residual photopic b-wave - CNGA3: 9.27 µV (n = 2) and CNGB3: 16.67 µV (n = 6) (Normal: 163.4 µV ± 37.6SD). OCT images were available for all 14 patients. Six CNGA3 patients showed foveal atrophy with loss of the foveal inner segment-outer segment line (IS-OS). One CNGA3 patient who had multiple longitudinal OCTs exhibited progressive foveolar cavitation. Two CNGB3 patients exhibited photoreceptor loss confined to the fovea; four other patients had broader photoreceptor loss. In patients with focal foveal atrophy, older patients in both mutation groups tended to have a larger area of foveolar cavitation. Three patients exhibited sparing of the foveal IS-OS line despite demonstrating no recordable cone function on ERG.
Our OCT data suggests that patients with CNGA3 and CNGB3 mutations exhibit progressive foveolar cone degeneration with cavitation with age. As expected, such focal deterioration will not be captured by a full-field ERG. This suggests that prior to progressive structural deterioration, there may be a therapeutic window characterized by electrophysiological dysfunction and minimal structural defects. With gene therapy for achromatopsia imminent, this therapeutic window will be important to delineate, especially since many of these approaches focus on improving foveal photoreceptor function.
This PDF is available to Subscribers Only