Longitudinal assessment of foveal cone structure in blue cone monochromacy

Abstract

Purpose : Blue cone monochromacy (BCM) is a rare cone disorder arising from sequence variants in the OPN1LW /OPN1MW gene array. Knowledge about the rate and extent of progression is crucial both for the development of therapeutic strategies and for managing patient expectations; there is, however, limited quantitative longitudinal analysis of photoreceptor integrity in patients with BCM. Here we examined foveal cone structure over two imaging sessions in patients with genetically-confirmed BCM.

Methods : Fifteen males (aged 8-51 years at first visit) harboring BCM-associated alterations in the OPN1LW/OPN1MW gene array were recruited for serial imaging. Where possible, thickness and integrity of retinal layers at the fovea was evaluated using optical coherence tomography (OCT), and the foveal cone mosaic was assessed using split-detection adaptive optics scanning light ophthalmoscopy (AOSLO). Axial eye length was measured and used to scale all images. Time between visits ranged from 6 months to 8 years. Imaging took place either at the Medical College of Wisconsin, USA or at University College London / Moorfields Eye Hospital, UK.

Results : Ten patients harbored the Cys203Arg point mutation, 3 had deletions of the locus control region (LCR), and 2 had the LVVVA interchange haplotype. OCT revealed reduced foveal thickness (34-84% of normal,¹n = 15) and AOSLO revealed reduced foveal cone density (12-54% of normal,²n = 8). Large variation in cone spacing was observed, with inter-cell regularity ranging from 42% to 105% of normal.² Quantitative serial analysis was achieved in 12 subjects for OCT, and a subset of 4 subjects for AOSLO. A paired t-test showed no statistically significant change in either total retinal thickness (p = 0.75) or cone density (p = 0.94) at the fovea over the two visits. However, degradation of outer retinal bands was observed in OCT images for 2 patients: 1 with the LVVVA haplotype (3-year period) and 1 with an LCR deletion (7-year period).

Conclusions : Our results suggest that most patients with BCM show minimal progression. Many appear to have remnant L/M cone structure, which likely depends on genotype, and the phenotype is highly variable. Thus, treatment efforts to restore cone function may not be viable in all BCM patients and should be assessed on an individualized basis.

This is a 2020 ARVO Annual Meeting abstract.

 

Cone density as a function of age in BCM.

 

Longitudinal imaging of the foveal cone mosaic in BCM.