Imaging Cone Structure in Patients with OPN1LW and OPN1MW Mutations

Abstract

 

Purpose

 

Adaptive optics (AO) retinal imaging in inherited color vision defects has shown that while most patients have normal contiguous cone mosaics, some can have mosaics of reduced density and/or cones with altered reflectivity. We examined the integrity of the cone mosaic in patients with OPN1LW and OPN1MW mutations, using a new split-detector AO scanning light ophthalmoscope (AOSLO) that captures multiply scattered light, enabling visualization of structures that scatter rather than directly reflect light (e.g., cone inner segments).

 

Methods

 

Eight subjects were imaged using AOSLO with either confocal and/or split-detection: A male with deuteranopia due to a combination of polymorphic amino acids (LIAVA) in the OPN1MW gene, 2 males with blue cone monochromacy (BCM) due to a C203R substitution in both the OPN1LW and OPN1MW genes, 2 female carriers of BCM from the same family, and 3 males with normal color vision.

 

Results

 

The male with deuteranopia had numerous gaps in his cone mosaic with confocal AOSLO, cone density was ~30% below normal. There was no change in cone density at 0.75° since the measurement 2 years ago (45,600 versus 44,000 cones/mm²), consistent with previous data showing no changes over an 8-year period. Split-detector AOSLO revealed that these gaps contained residual cone inner segment structure. In one of the males with BCM, we observed presumed cone inner segment structure throughout the fovea using the split-detector method (16,500 cones/mm²). In the BCM males and female carriers, confocal AOSLO images revealed gaps in the mosaic, and split-detector AOLSO revealed remnant inner segment structure in these gaps.

 

Conclusions

 

Diminished reflective signal in confocal AOSLO images is likely indicative of disrupted outer segment structure. However, as shown by the split-detector AOSLO imaging, this does not mean there is absence of the photoreceptor cell. Split-detector AOSLO imaging will be essential for accurate assessment of cone disruption associated with various OPN1LW and OPN1MW mutations.

 

 

Comparison of confocal AOSLO images shown in logarithmic gray scale (left) and corresponding split detector AOSLO images (right) from a subject with deuteranopia caused by an LIAVA polymorphism in the OPN1MW gene. Arrowheads in the top panels show examples of cones with diminished or absent reflectivity in the confocal image but normal inner segment structure on the split-detector image. Scale bar = 50 microns.

 

Keywords: 471 color vision • 550 imaging/image analysis: clinical • 648 photoreceptors