Foveal Cone Structure in Patients With Blue Cone Monochromacy

Abstract

Purpose Blue cone monochromacy (BCM) is a rare inherited cone disorder in which both long- (L-) and middle- (M-) wavelength sensitive cone classes are either impaired or nonfunctional. Assessing genotype-phenotype relationships in BCM can improve our understanding of retinal development in the absence of functional L- and M-cones. Here we examined foveal cone structure in patients with genetically-confirmed BCM, using adaptive optics scanning light ophthalmoscopy (AOSLO). Methods Twenty-three male patients (aged 6–75 years) with genetically-confirmed BCM were recruited for high-resolution imaging. Eight patients had a deletion of the locus control region (LCR), and 15 had a missense mutation—Cys203Arg—affecting the first two genes in the opsin gene array. Foveal cone structure was assessed using confocal and non-confocal split-detection AOSLO across a 300 × 300 µm area, centered on the location of peak cell density. Results Only one of eight patients with LCR deletions and 10 of 15 patients with Cys203Arg mutations had analyzable images. Mean total cone density for Cys203Arg patients was 16,664 ± 11,513 cones/mm 2 (n = 10), which is, on average, around 40% of normal. Waveguiding cone density was 2073 ± 963 cones/mm 2 (n = 9), which was consistent with published histological estimates of S-cone density in the normal eye. The one patient with an LCR deletion had a total cone density of 10,246 cones/mm 2 and waveguiding density of 1535 cones/mm 2 . Conclusions Our results show that BCM patients with LCR deletions and Cys203Arg mutations have a population of non-waveguiding photoreceptors, although the spectral identity and level of function remain unknown.

Unique Haplotypes in OPN1LW as a Common Cause of High Myopia With or Without Protanopia: A Potential Window Into Myopic Mechanism

“… 4 , 28 Subsequently, a single L-M hybrid gene with an inactivating missense mutation (p.C203R) or truncation variant was shown to result in BCM, a severe phenotype caused by the complete absence of L and M cone function. 29 – 31 High homology between OPN1LW and OPNMW contributes to numerous polymorphisms with allele frequencies greater than 1% in general population. 1 Combination of 5 polymorphisms in exon 3 forms various haplotypes with exon skipping impacts to different degrees.…”

S-cone contribution to oscillatory potentials in patients with blue cone monochromacy

“…The fundus usually appears normal in both diseases, although ACHM tends to exhibit fovea hypoplasia more frequently than in BCM individuals [ 25 ]. Alterations in foveal thickness were found with spectral-domain optical coherence tomography (SD-OCT) in both diseases.…”