Abstract
Purpose :
CLN2 disease is progressive neurodegenerative disorder affecting the brain and retina. Children at the age of 3-4 years present with motor and cognitive decline, epileptic seizures and progressive visual deterioration. Since end 2017 a FDA and EMA approved enzyme replacement therapy via an intracerebroventricular (ICV) approach with cerliponase alpha (Brineura, BioMarin Pharmaceutical) effectively alters the course of the disease. In contrast, retinal degeneration has not been investigated in neither naive or systemically treated patients with CLN2 disease.
The presented cross-sectional study investigates the retinal degeneration in CLN2 patients with the aid of optical coherence tomography (OCT) imaging.
Methods :
20 eyes of 10 patients with genetically confirmed CLN2 disease are included into this study. Under the commercially available therapy of cerliponase alpha, patients were assessed with slit lamp microscopy, funduscopy, OCT imaging (Leica Bioptigen Envisu C2300). Manual CRT, 300 μm nasal and temporal to the fovea, the total retinal thickness was analyzed. Statistical correlation between age and retinal thickness in classic, late infantile CLN2 patients was performed.
Results :
OCT based central retinal thickness (CRT) was reduced in all patients. A mean reduction of 28 μm (SD 11.8 μm) per year was observed, resulting in a homogenous and steady in reduction of CRT. A negative correlation between CRT and age was observed. A statistically more significant retinal degeneration was observed in patients with late infantile CLN2 disease as compared to the juvenile course of CLN2 disease.
Conclusions :
We highlight the progressive retinal atrophy contributing to visual deterioration in CLN2 disease despite an ICV approved enzyme replacement therapy. The ongoing retinal degeneration outlines the unmet demand of an adjunctive ocular therapeutical approach in order to prevent blindness. In addition, objective and non invasive OCT imaging resembles a precise tool to collect retinal natural history for upcoming clinical trials.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.