Abstract
Purpose :
To describe the clinical characteristics and natural history of Leber congenital amaurosis (LCA) associated with disease-causing variants in GUCY2D (LCA-GUCY2D) and consider implications for treatment.
Methods :
In this retrospective study, clinical notes; including demographic data, symptoms at presentation and visual acuity, retinal imaging; colour fundus photography, and optical coherence tomography (OCT), and electroretinography (ERG) of molecularly confirmed GUCY2D-LCA subjects were reviewed.
Results :
Twenty-two subjects with LCA-GUCY2D were included with an age range at first examination of 0 – 60 years old, and a mean follow up ± standard deviation (SD) of 10 ± 11.85 years. A marked reduction of VA and nystagmus were documented in all patients within the first 3 years of life. Photophobia was documented in 54% (n=12) and nyctalopia in 36% (n=8). Presenting VA was worse than hand movements (HM) in 75% (n=20). Longitudinal assessment of VA showed stability in all patients, except one patient who experienced deterioration of LogMAR VA from 0.78 bilaterally, to 1 and 1.3 in the right and left eyes respectively, over a follow-up of 44 years. Hyperopia greater than +6.5 dioptres was recorded in 59% (n=13) of the 18 subjects with available data. On CFP, 77% (n=17) had a normal (n=14) or blonde fundus appearance (n=3), while 3 of the oldest subjects had mild macular atrophy of the retinal pigments epithelium (RPE), (mean age 49 years; range 40-54). On OCT (available for 11 patients), 4 different grades of ellipsoid zone (EZ) integrity were identified; continuous/intact (n=6), focally disrupted (n=2), focally disrupted with RPE changes (n=2), and absent with RPE changes (n=1). EZ was present in 91% (n=10) patients (mean age ±SD; 35.1±23.4 years). Full-field ERG was undetectable in the 17 patients for whom data was available.
Conclusions :
LCA-GUCY2D is a severe early-onset retinopathy. However, although photoreceptor function is substantially affected, the relatively well preserved EZ on OCT over a broad age range suggests a wide therapeutic window of opportunity.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.