Juvenile CLN3 disease, the most prevalent form of Batten disease, is a progressive neurodegenerative disorder resulting from mutations in the CLN3 gene. The objective of this study was to design an op Show more
Juvenile CLN3 disease, the most prevalent form of Batten disease, is a progressive neurodegenerative disorder resulting from mutations in the CLN3 gene. The objective of this study was to design an ophthalmic rating scale for CLN3 disease in order to quantify disease progression. Retrospective, cross-sectional study. Patients underwent ophthalmic evaluations including visual testing, optical coherence tomography and fundus imaging. Patients were also assessed using the Hamburg Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) scoring system. Ophthalmic findings were divided into grades of severity ranging from 0 to 3, and the association between the extent of ocular disease and neurological function and age was assessed. Forty-two eyes of 21 patients were included. The mean age at the time of examination was 13.2 years (range, 5.3-21.9 years). The mean ophthalmic severity grade was 2.4 (range, 0-3). The mean neurological severity score was 9.9 (range, 4-14). Ophthalmic manifestations increased in severity with increasing age of the patients (r = -0.84; P < .001), and a strong correlation was found between the CLN3 ophthalmic rating scale score and the Hamburg JNCL score (r = 0.83; P < .001). Ophthalmic manifestations of CLN3 disease correlate closely with the severity of neurological symptoms and age of the patient. The newly established Hamburg CLN3 ophthalmic rating scale may serve as an objective marker of ocular disease severity and progression and may be valuable tool for the evaluation of novel therapeutic strategies for CLN3 disease. Show less
Juvenile CLN3 disease, one of the most common forms of a group of lysosomal storage diseases called neuronal ceroid lipofuscinoses (NCLs), is a progressive neurodegenerative disorder with initial visu Show more
Juvenile CLN3 disease, one of the most common forms of a group of lysosomal storage diseases called neuronal ceroid lipofuscinoses (NCLs), is a progressive neurodegenerative disorder with initial visual deterioration. The objective of this study was to analyse the retinal phenotype of patients with CLN3 disease with the help of recent ophthalmic imaging modalities to distinguish CLN3 disease from other inherited retinal dystrophies. Patients underwent ophthalmic evaluations, including anterior and posterior segment examinations, optical coherence tomography, fundus autofluorescence, near infrared imaging and fundus photography. Patients were also assessed according to the Hamburg juvenile NCL (JNCL) score. Each ophthalmic finding was assessed by three independent examiners and assigned to a clinical severity score. 22 eyes of 11 patients were included. The mean age at examination was 14.4 years (range 11.8-26.4 years), with an average age at initial diagnosis of 8 years (range 4.5-11 years). The mean Hamburg JNCL score was 7.3 (range 0-13). All patients showed a specific macular striation pattern on optical coherence tomography that was independent of age and progression of the disease. Other previously described retinal features of CLN3 disease were classified into four severity grades. This study represents the first prospective observational case series documenting retinal abnormalities in CLN3 disease with the aid of the spectral domain optical coherence tomography. The major finding was a characteristic, striated macular pattern in all patients studied. Particularly in early disease cases, macular striae can potentially help to discriminate CLN3 disease from other inherited forms of retinitis pigmentosa. Show less