Abstract
Hemizygous pathogenic variants in CACNA1F lead to defective signal transmission from retinal photoreceptors to bipolar cells and cause incomplete congenital stationary night blindness in humans. Although the primary defect is at the terminal end of first-order neurons (photoreceptors), there is limited knowledge of higher-order neuronal changes (inner retinal) in this disorder. This study aimed to investigate inner retinal changes in CACNA1F-retinopathy by analyzing macular ganglion cell layer-inner plexiform layer (GCL-IPL) thickness and optic disc pallor in 22 subjects with molecularly confirmed CACNA1F-retinopathy. Detailed ocular phenotypic data including distance and color vision, refraction and electroretinogram (ERG) were collected. Distance vision was universally reduced (mean: 0.42 LogMAR), six had abnormal color vision and myopia was common (n = 15; mean: −6.32 diopters). Mean GCL-IPL thickness was significantly lower in patients (55.00 µm) compared to age-matched controls (n = 87; 84.57 µm; p << 0.001). The GCL-IPL thickness correlated with scotopic standard (p = 0.04) and bright-flash (p = 0.014) ERG b/a ratios and photopic b-wave amplitudes (p = 0.05). Twenty-one patients had some degree of disc pallor (bilateral in 19). Fifteen putative disease-causing, including five novel variants were identified. This study establishes macular inner retinal thinning and optic atrophy as characteristic features of CACNA1F-retinopathy, which are independent of myopia and could impact potential future treatment strategies.
Highlights
Congenital stationary night blindness (CSNB) is a group of genetically and phenotypically heterogeneous retinal disorders that follow autosomal dominant, autosomal recessive or X-linked patterns of inheritance and can be broadly categorized into those with a largely normal, or an abnormal, fundus appearance [1]
Both cCSNB and iCSNB show phenotype–genotype correlation, with genes involved in cCSNB encoding proteins mainly localized to post-synaptic retinal ON-bipolar cells, while genes responsible for iCSNB affect proteins predominantly expressed at the terminal end of the photoreceptor synapse, affecting both ON- and OFF-bipolar signaling [1]
Two of the three patients who had Magnetic resonance imaging (MRI) to evaluate for optic atrophy were found to have unremarkable optic nerves and one displayed bilateral, mild changes compatible with optic nerve atrophy
Summary
Congenital stationary night blindness (CSNB) is a group of genetically and phenotypically heterogeneous retinal disorders that follow autosomal dominant, autosomal recessive or X-linked patterns of inheritance and can be broadly categorized into those with a largely normal, or an abnormal, fundus appearance [1]. On photopic (light adapted; LA) ERG testing, iCSNB subjects demonstrate markedly reduced a- and b-wave amplitudes to a standard flash (3.0 cd·s·m−2) and reduced 30 Hz flicker amplitudes, whereas cCSNB subjects exhibit subtle abnormalities to standard flash (broadened a-wave trough and a mildly reduced b-wave amplitude) and 30 Hz flicker (delayed and square-shaped trough) stimuli [1,8,9] Both cCSNB and iCSNB show phenotype–genotype correlation, with genes involved in cCSNB encoding proteins mainly localized to post-synaptic retinal ON-bipolar cells, while genes responsible for iCSNB affect proteins predominantly expressed at the terminal end of the photoreceptor synapse, affecting both ON- and OFF-bipolar signaling [1]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
