Abstract
Achromatopsia has been proposed to be a morphologically predominately stable retinopathy with rare reports of progression of structural changes in the macula. A five-grade system of optical coherence tomography (OCT) features has been used for the classification of structural macular changes. However, their association with age remains questionable. We characterized the Slovenian cohort of 12 patients with pathogenic variants in CNGA3 or CNGB3 who had been followed up with OCT for up to 9 years. Based on observed structural changes in association with age, the following four-stage classification of retinal morphological changes was proposed: (I) preserved inner segment ellipsoid band (Ise), (II) disrupted ISe, (III) ISe loss and (IV) ISe and RPE loss. Data from six previously published studies reporting OCT morphology in CNGA3 and CNGB3 patients were additionally collected, forming the largest CNGA3/CNGB3 cohort to date, comprising 126 patients aged 1–71 years. Multiple regression analysis showed a significant correlation of OCT stage with age (p < 0.001) and no correlation with gene (p > 0.05). The median ages of patients with stages I–IV were 12 years, 23 years, 27 years and 48 years, respectively, and no patient older than 50 years had continuous ISe. Our findings suggest that achromatopsia presents with slowly but steadily progressive structural changes of the macular outer retinal layers. However, whether morphological changes in time follow the proposed four-stage linear pattern needs to be confirmed in a long-term study.
Highlights
Achromatopsia (ACHM) is a complex inherited retinal disorder primarily affecting the cone cell function [1], the incidence being around 1:30,000 births
The study included 12 patients from 9 families recruited from the Eye Hospital, University Medical Centre Ljubljana (UMC LJ), Slovenia, who had been referred for genetic testing due to suspected inherited retinal disease (IRD) and had confirmed biallelic pathogenic or likely pathogenic variants in CNGA3 (n = 7) or CNGB3 (n = 5)
Other ACHM-related genes are routinely screened in patients with suspected IRDs, no other ACHM-related genes were identified in patients from UMC LJ, which is the only tertiary center overseeing IRD
Summary
Achromatopsia (ACHM) is a complex inherited retinal disorder primarily affecting the cone cell function [1], the incidence being around 1:30,000 births. The mode of ACHM inheritance is autosomal recessive with currently six known causative genes: CNGA3 [4], CNGB3 [5], GNAT2 [6], PDE6C [7], PDE6H [8] and ATF6 [9]. The majority of causative genes (with the exception of ATF6) are involved in the conespecific phototransduction cascade. CNGA3 and CNGB3 genes encode the alpha and beta subunits of the cyclic nucleotide-gated ion channels, respectively, located in the plasma membrane of outer cone segments [10,11]. There are over 150 known pathogenic variants in both CNGA3 and CNGB3 genes, accounting for over 70% of all ACHM cases [1]
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