Optic Atrophy and Inner Retinal Thinning in CACNA1F-related Congenital Stationary Night Blindness

Genes (Basel). 2021 Feb 25;12(3):330. doi: 10.3390/genes12030330.


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.

Keywords: CACNA1F; calcium channels/genetics; electroretinography; eye diseases; hereditary; myopia; night blindness/congenital; optic atrophy; optical coherence; retinal bipolar cells; retinal ganglion cells; tomography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Electroretinography
  • Eye Diseases, Hereditary / diagnostic imaging*
  • Eye Diseases, Hereditary / genetics
  • Eye Diseases, Hereditary / pathology
  • Female
  • Genetic Diseases, X-Linked / diagnostic imaging*
  • Genetic Diseases, X-Linked / genetics
  • Genetic Diseases, X-Linked / pathology
  • Humans
  • Male
  • Middle Aged
  • Myopia / diagnostic imaging*
  • Myopia / genetics
  • Myopia / pathology
  • Night Blindness / diagnostic imaging*
  • Night Blindness / genetics
  • Night Blindness / pathology
  • Optic Atrophy / diagnostic imaging
  • Optic Atrophy / pathology*
  • Refraction, Ocular
  • Retina / diagnostic imaging
  • Retina / pathology*
  • Retrospective Studies
  • Tomography, Optical Coherence / methods*
  • Young Adult

Supplementary concepts

  • Night blindness, congenital stationary