Retinal Development in Achromatopsia: A Prospective Study of Infants and Young Children using Optical Coherence Tomography

Abstract

Purpose: To characterize postnatal retinal development in infants and young children with achromatopsia using hand-held spectral domain optical coherence tomography (HH-SDOCT) and to investigate whether retinal changes are progressive.<br />

Methods: Forty-one mixed cross-sectional and longitudinal HH-SDOCT images were obtained from eight infants and young children with achromatopsia (mean age 3.3 years; range 0-8.3 years) and compared with 82 age-matched control examinations. All patients had homozygous mutations in either CNGA3 (n=2) or CNGB3 (n=6). Retinal layer segmentation was performed manually using ImageJ. Differences in development of retinal layers with age between the achromatopsia and control groups were analysed using linear mixed regression modelling. The severity and progression of photoreceptor disruption was evaluated in all participants with longitudinal data (11 eyes of 6 participants; mean follow-up time 14.8 months; range 7.2-20.9 months).<br />

Results: In achromatopsia, retinal thickness increased more slowly with age and was reduced at the fovea in comparison to controls (p < 0.05). There was delayed regression of the inner retinal layers (IRLs) at the fovea and a reduction in the thickness of the perifoveal IRLs. This was especially significant for the perifoveal inner (p < 0.0001) and outer (p < 0.01) plexiform layers. Elongation of the outer retinal layers (ORLs) was diminished across the retina resulting in a significant reduction in ORL thickness, especially at the fovea (p < 0.0001). There was evidence of an increase (4 eyes), decrease (1 eye) and no change (2 eyes) in the grade of photoreceptor disruption on longitudinal assessment. Interestingly, in 4 eyes both an increase and decrease in the grade of photoreceptor disruption was observed at different time points.<br />

Conclusions: Previously, it has been thought that retinal development is arrested in achromatopsia. We demonstrate ongoing retinal development in achromatopsia in the postnatal period albeit at an altered rate and magnitude in comparison to controls. Achromatopsia appears to be a dynamic and progressive condition in infants and young children. This has potential implications for planned gene therapy, since intervention at the earliest stages of the disease may promote normal retinal development.<br />