High resolution images of cone photoreceptors with Bietti Crystalline dystrophy associated with CYP4V2 mutation

Abstract

Purpose: To study the retinal morphology of eyes with Bietti crystalline dystrophy (BCD) associated a CYP4V2 mutation using high-resolution imaging techniques.

Methods: Retinal images were obtained from three subjects with BCD. Mutation screening of all coding and flanking intron sequences of the CYP4V2 gene were performed by DNA sequencing analyses. High resolution images were obtained with a flood-illuminated adaptive optics (AO) fundus camera (rtx1™, Imagine eyes, France). The illumination beam was successively aligned with 3 different locations in the eye’s pupil: the center and the periphery on the nasal and temporal sides.When small bright spot structures were visible in the resulting images, the variations of their brightness with changes in beam location were examined in order to detect the existence of optical Stiles-Crawford effect, which was used to identify cone photoreceptors. Other retinal images were obtained by spectral domain optical coherence tomography (SD-OCT) and infrared fundus photography.

Results: Funduscopic examination of the three patients revealed the presence of small, yellowish-white crystalline deposits located within the vascular arcades. A homozygous deletion/insertion mutation, g.IVS6-8_-1delc.802_810del/insGC including the 3’-acceptor splice site, was detected in the three patients. SD-OCT analyses showed brightly reflective plaques located on the RPE layer. These bright plaques corresponded with the crystalline deposits in the fundus photographs and infrared images. The locations of these crystals also corresponded with areas where microscopic bright spots were also visible in the AO images. Although the distribution of these spots was irregular in comparison with a healthy cone mosaic, they showed optical Stiles-Crawford effect when the illumination beam location was varied. There results indicate that these spots might be cone photoreceptors.

Conclusions: Our observation that cones like bright spots were located over the crystalline deposits suggests that the crystals are not the cause of the decrease in visual function. This is supported by the development of RPE and choroidal atrophy only after the crystals are no longer detected.This would indicate that the pathology of the retina is not directly correlated with the presence of the crystalline deposits.

Keywords: 494 degenerations/dystrophies • 539 genetics • 550 imaging/image analysis: clinical