Peripapillary Retinal Nerve Fiber Layer (pRNFL) Thickness – A Novel Biomarker of Neurodegeneration in Late-Infantile CLN2 Disease

Abstract

Nikolaos Gkalapis,1,2,* Simon Dulz,1,* Carsten Grohmann,1 Miriam Nickel,3 Christoph Schwering,3 Eva Wibbeler,3 Martin Stephan Spitzer,1 Angela Schulz,3 Yevgeniya Atiskova1 1Department of Ophthalmology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 2Department of Ophthalmology, University Hospital of Martin Luther University Halle/Wittenberg, Halle (Saale), Germany; 3Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany*These authors contributed equally to this workCorrespondence: Yevgeniya Atiskova, Department of Ophthalmology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg, 20246, Germany, Tel [phone] – 52301, Fax [phone] – 42301, Email [email protected]: To investigate the presence of peripapillary retinal nerve fiber layer (pRNFL) degeneration in patients with late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease and to evaluate the role of optical coherence tomography (OCT) assessed pRNFL thickness as a biomarker for CLN2 disease progression.Patients and Methods: Forty eyes of 20 patients with genetically and enzymatically confirmed diagnosis of late-infantile CLN2 disease were included in this retrospective cohort study. All patients received 300 mg of intracerebroventricular enzyme replacement treatment (cerliponase alfa) once every two weeks. OCT imaging was performed under general anesthesia using spectral domain OCT (Heidelberg Engineering, Heidelberg, Germany). PRNFL thickness and central retinal thickness (CRT) values were manually confirmed with the Heidelberg Eye Explorer software. Corresponding pediatric data were extracted from the DEM-CHILD database. Spearman correlation coefficient values (rs) were calculated between pRNFL and CRT values, age at examination, the Weill Cornell Late Infantile Neuronal Ceroid Lipofuscinosis (Weill Cornell LINCL) Scale and the Hamburg Motor and Language (HML) Scale.Results: Fourteen of 20 patients underwent serial examinations resulting in a total of 84 OCT Scans and 42 Weill Cornell LINCL and HML Scale scores. Mean age was 6.90 years and mean follow-up time was 1.38 years. Mean global pRNFL (G-pRNFL) thickness was 77.02 μm presenting a significant decrease compared to normative values from healthy children (106.45 μm; p < 0.0001). G-pRNFL displayed significant correlations towards age at examination (rs = - 0.557, p < 0.01), the Weill Cornell LINCL Scale (rs = 0.849, p < 0.01), and the HML Scale (rs = 0.833, p < 0.01). Repeated measurements indicated decreases in pRNFL thickness over time in most patients.Conclusion: Patients with late-infantile CLN2 disease exhibit early onset progressive pRNFL loss regardless of outer retinal degeneration, highlighting the potential of pRNFL as an independent ocular biomarker for retinal pathology in late-infantile CLN2 disease.Keywords: neuronal ceroid lipofuscinosis, optic nerve, optical coherence tomography, retina, neurodegeneration, eye

Keywords

• neuronal ceroid lipofuscinosis
• optic nerve
• optical coherence tomography
• retina
• neurodegeneration
• eye