Abstract
Purpose :
Ocular abnormalities, including retinal dystrophy, are reported in patients with Alagille syndrome (ALGS), but it is unknown whether visual and retinal function decline with age. In a combined retrospective and prospective study, visual and retinal function in patients with molecularly-confirmed ALGS were studied for significant changes over time.
Methods :
Twenty patients, ranging in age from 0.1 to 28.3 (median 7.7) years, with loss-of-function mutations in JAG1 (n=19) or NOTCH2 (n=1) were identified. Comprehensive ophthalmic evaluations including best corrected visual acuity, cycloplegic refraction, dark adapted visual threshold, and full-field electroretinography (ffERG) were conducted. Longitudinal data over 2 to 24 (median 4) years were available for nine patients. Serial multifocal electroretinography (mfERG) was done for one patient with maculopathy. Parameters of these tests were evaluated cross sectionally and longitudinally for significant change with age.
Results :
Acuity (Δ log normal for age) showed a decline with increasing age (p=0.01) of approximately 2-3 lines per decade. The decline was not limited to those with identified retinal dystrophy. High refractive errors, either myopia or hyperopia, were common; the spherical equivalent was outside the prediction interval of normal for age in half of the patients; it did not vary significantly with age. The dark adapted visual threshold was elevated on the first test (median 1.57; range 0 to 3.12 log units) , it did not change significantly with age. Scotopic and photopic ffERG responses were markedly attenuated (amplitudes ≤10%) in all but one patient whose amplitudes were ∼ 25% of the normal mean. Amplitudes, although low, were stable for up to 24 years. In a patient with maculopathy tested longitudinally over 17 years, mfERG amplitudes remained low but stable.
Conclusions :
In patients with ALGS, although functional parameters are significantly compromised, many remain stable over time. The decline in visual acuity is concerning. In the continuing project, we will further characterize retinal function and structure to test hypotheses about the basis for the declining acuity.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.