Wide-field true-colour imaging and clinical characterization of a novel GRK1 mutation in Oguchi disease

Purpose: The available literature regarding Oguchi disease is limited, with around 50 cases described to date. Caused by mutations to either the SAG gene coding for arrestin (Hayashi et al. in Ophthalmic Res 46:175-180, 2011) or the GRK1 gene coding for rhodopsin kinase (Yamamoto et al. in Nat Genet 15:175-178. https://doi.org/10.1038/ng0297-175 , 1997), Oguchi disease is an autosomal recessive condition with a good visual prognosis. The clinical diagnosis of the condition is based on the presence of night blindness (nyctalopia), as well as fundoscopic observation of the Mizuo-Nakamura phenomenon. The Mizuo-Nakamura phenomenon refers to a fundus discolouration described as a golden-brown colour with a yellow-grey metallic sheen most prominent in the peripheral retina; after prolonged dark adaptation, the fundus appears normal. The prevalence of Oguchi disease is highest in Japan, particularly with SAG mutations (Nakazawa et al. in Retina 17:17-22, 1997), although patients from Europe, Pakistan and India have also been described. Formal diagnosis requires genetic testing.

Methods: Wide-field fundus images were obtained in both dark-adapted and light-adapted retina. Optical coherence tomography and dark-adapted electroretinography responses were used to further characterize the clinical phenotype.

Results: Existing descriptions of Oguchi disease have been limited by available technology. The flashes required for 45°-montage photographs in a dark-adapted eye quickly cause light adaptation. Recent advances in technology enable the capture of larger retinal areas in a single image. Wide-field 133° images were obtained of the native and dark-adapted fundus in natural colour. To our knowledge, these represent the first reported single-wide-field images of Oguchi disease, showing the characteristic Mizuo-Nakamura phenomenon in true colour. Genetic testing revealed a novel homozygous mutation in GRK1.

Conclusions: Here, we demonstrate how characterizing this condition with single-shot true-colour wide-field imaging has distinct advantages over scanning laser technology, which applies artificial colouration, or stitched true-colour images. Images captured with wide-field systems create a much better representation of the native and dark-adapted fundus than can be observed by the ophthalmologist using direct fundoscopy and are essential in the clinical characterization of new mutations.