Progressive retinal degeneration despite intraventricular enzyme replacement therapy with cerliponase alfa in classic late-infantile CLN2 disease

Abstract

Purpose : Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) is a neurodegenerative, blinding lysosomal storage disorder. The purpose of the current study was to characterize the progression of CLN2-associated retinal degeneration in patients under intraventricular enzyme replacement therapy (ERT) with cerliponase alfa.

Methods : We analyzed visual function, retinal morphology and neuropediatric data using preferential looking test (PLT), Weill Cornell Batten Scale (WCBS), OCT imaging and the Hamburg motor-language scores (M-L score).

Results : Fifty-six eyes of 28 patients had baseline PLT, WCBS and OCT. 15 patients underwent serial examinations, resulting in a total of 132 OCT scans and WBCS results, 67 Hamburg M-L scores and 49 PLT results during a mean follow up time of 18.2 months (range 5-40). A negative correlation (r=-.69, p<0.001) was found between CRT and age at exam with a maximum annual decrease (23 µm) within the time intervals 56-80 months. A significant correlation was observed between the PLT and the age at examination (r= .46, p=0.001), the WBCS (r= .62; p<0.001) and CRT (r=-.64; p<0.001). The M-L score correlated with the ocular measurements (CRT: r= .58, p<0.001; WCBS r= -.64, p<0.001; PLT score: r= -.57, p<0.001).

Conclusions : Despite intraventricular ERT, retinal degeneration associated with CLN2 disease manifests as a progressive decline, which appears to accelerate during a critical period at 56 to 80 months of age. Retina-specific therapy should occur ideally before or as early as possible within this period. PLT, WCBS are valuable outcome measures to monitor disease progression.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.