Retinal Structure and Visual Function in Patients with Blue Cone Monochromatism

Abstract

Purpose: : To determine the detailed phenotype of blue cone monochromatism (BCM) caused by red/green opsin gene mutations.

Methods: : Patients with deletions within the red/green opsin gene cluster (ages 5 to 48 years) were included. Vision was assessed clinically and with rod and cone static perimetry. Microperimetry was used to visualize the location and stability of fixation. Central retinal structure was analyzed using optical coherence tomography (OCT) and near-infrared autofluorescence (NIR-AF).

Results: : BCM patients presented with impaired visual acuity of varying severities. Fixation was extrafoveal and unstable. The eccentricity of fixation from the anatomical fovea (ranging from 1 to 4 degrees) correlated inversely with logMAR acuity. L/M cone sensitivity losses were present in all patients. There was reduced outer nuclear layer thickness across the central retina and there were cone outer segment laminar abnormalities. These retinal structural abnormalities were present from the earliest ages studied. BCM patients also had a subnormal (or borderline normal) rod outer segment layer and some had slightly reduced rod sensitivity. Patients in the 5th decade of life showed a foveal hypo-reflective zone or loss of all detectable foveal ONL with accompanying central sensitivity losses. NIR-AF intensity tended to be near the lower limit of normal except for the foveal regions of the older patients in which there were RPE melanin abnormalities corresponding to the central OCT lesions.

Conclusions: : BCM caused by deletions in the red/green opsin gene cluster classically manifests as early-onset L/M cone dysfunction. The present study indicates that this is not a pure dysfunction that later leads to a macular degeneration, but rather a condition with detectable cone photoreceptor structural abnormalities even in the first decade of life. Future clinical treatment trials must take this early foveal (central retinal) fragility into consideration and adjust therapeutic strategies accordingly.

Keywords: retina • retinal degenerations: hereditary • imaging/image analysis: clinical