title: Spectrum of ocular manifestations in CLN2-associated batten (Jansky-Bielschowsky) disease correlate with advancing age and deteriorating neurological function.
abstract: BACKGROUND
  Late infantile neuronal ceroid lipofuscinosis (LINCL), one form of Batten's disease is a progressive neurodegenerative disorder resulting from a CLN2 gene mutation. The spectrum of ophthalmic manifestations of LINCL and the relationship with neurological function has not been previously described.
  
  
  METHODS
  Patients underwent ophthalmic evaluations, including anterior segment and dilated exams, optical coherence tomography, fluorescein and indocyanine green angiography. Patients were also assessed with the LINCL Neurological Severity Scale. Ophthalmic findings were categorized into one of five severity scores, and the association of the extent of ocular disease with neurological function was assessed.
  
  
  RESULTS
  Fifty eyes of 25 patients were included. The mean age at the time of exam was 4.9 years (range 2.5 to 8.1). The mean ophthalmic severity score was 2.6 (range 1 to 5). The mean neurological severity score was 6.1 (range 2 to 11). Significantly more severe ophthalmic manifestations were observed among older patients (p<0.005) and patients with more severe neurological findings (p<0.03). A direct correlation was found between the Ophthalmic Severity Scale and the Weill Cornell Neurological Scale (p<0.002). A direct association was also found between age and the ophthalmic manifestations (p<0.0002), with older children having more severe ophthalmic manifestations.
  
  
  CONCLUSIONS
  Ophthalmic manifestations of LINCL correlate closely with the degree of neurological function and the age of the patient. The newly established LINCL Ophthalmic Scale may serve as an objective marker of LINCL severity and disease progression, and may be valuable in the evaluation of novel therapeutic strategies for LINCL, including gene therapy.
authors.affiliation: Department of Ophthalmology, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Anton
authors.initials: A
authors.lastname: Orlin
authors.forename: Dolan
authors.initials: D
authors.lastname: Sondhi
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Witmer
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Wessel
authors.forename: Jason G
authors.initials: JG
authors.lastname: Mezey
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Kaminsky
authors.forename: Neil R
authors.initials: NR
authors.lastname: Hackett
authors.forename: Kaleb
authors.initials: K
authors.lastname: Yohay
authors.forename: Barry
authors.initials: B
authors.lastname: Kosofsky
authors.forename: Mark M
authors.initials: MM
authors.lastname: Souweidane
authors.forename: Michael G
authors.initials: MG
authors.lastname: Kaplitt
authors.forename: Donald J
authors.initials: DJ
authors.lastname: D'Amico
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
authors.forename: Szilárd
authors.initials: S
authors.lastname: Kiss
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000626:Aminopeptidases / Q000235:genetics; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics; D005128:Eye Diseases / Q000209:etiology* / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000150:complications* / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D057057:Serine Proteases / Q000235:genetics; D012720:Severity of Illness Index; D000091346:Tripeptidyl-Peptidase 1
chemical_list: D000091346:Tripeptidyl-Peptidase 1; D057057:Serine Proteases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C000717267:TPP1 protein, human