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Jonathan Aboshiha, Adam M Dubis, Koji Miura Nishiguchi, Edward W Cheeseman, Carmen Ayuso, James W B Bainbridge, Michel Michaelides; Relative preservation of foveal outer retinal structure in infants with AIPL1 associated Leber’s Congenital Amaurosis: implications for gene therapy. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1416.
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AIPL1 mutations cause a rare but severe form of the inherited retinal dystrophy Leber’s congenital amaurosis (LCA). There has been successful rescue of animal models of AIPL1-LCA, which recapitulate human disease well, being of early-onset and rapidly progressive. To date, human clinical studies of adults and older children have suggested that photoreceptor cell loss occurs early in disease, thereby meaning that any potential window of opportunity to intervene is very early. In this study we have characterized molecularly proven infants/young children to help establish if gene therapy may be a viable consideration.
We collected data on molecularly confirmed AIPL1 patients including demographics, visual acuity, fundus examination, electrophysiological findings, spectral-domain optical coherence tomography (OCT), and genotype. In cases where standard chin-rest based OCT imaging was not possible, hand-held OCT was undertaken.
Data of 41 molecularly proven patients were reviewed, with 10 patients (24%) aged less than five years old. The commonest observed sequence variant was p.Trp278*, which was found in at least one allele in 21 patients (51%). OCT images were available for 17 patients (41%). In the two youngest patients in our cohort, each one year of age, there was evidence of significant outer retinal structure, with relative preservation of the inner segment ellipsoid (ISe) layer at the fovea.
To the best of our knowledge, the two youngest patients in our cohort represent the youngest children with AIPL1 LCA to be imaged to date. The relatively preserved outer retinal architecture identified in these two children suggests that any intervention may need to be initiated in the first few years of life. Serial imaging over time in these children will help to confirm the exact window of opportunity.
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