{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:59:16Z","timestamp":1789498756162,"version":"build-2803163510"},"reference-count":15,"publisher":"Georg Thieme Verlag KG","issue":"02","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropediatrics"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ceroid lipofuscinosis type 2 (CLN2) is caused by biallelic pathogenic variants in the TPP1 gene, encoding lysosomal tripeptidyl peptidase 1 (TPP1). The classical late-infantile phenotype has an age of onset between 2 and 4 years and is characterized by psychomotor regression, myoclonus, ataxia, blindness, and shortened life expectancy. Vision loss occurs due to retinal degeneration, usually when severe neurological symptoms are already evident.<\/jats:p><jats:p>Intracerebroventricular enzyme replacement therapy (ICV-ERT) using recombinant human TPP1 (rhTPP-1) was shown to slow the neurological decline; however, it does not prevent loss of vision. Intravitreal rhTPP-1 (IVT-ERT) was described to halt retinal degeneration in a canine CLN2 model and a compassionate-use study in humans.<\/jats:p><jats:p>We report on the clinical and ophthalmological outcome in an early-treated patient homozygous for a pathogenic variant in TPP1 known to be associated with severe CLN2 retinopathy.<\/jats:p><jats:p>He was started on ICV-ERT at the age of 40 months and 4 weekly IVT-ERT in one eye at the age of 60 months. The other eye served as untreated control.<\/jats:p><jats:p>Baseline best corrected visual acuity (BCVA) was 0.5 with mild bull's eye maculopathy evident in both eyes. After 24 months of IVT-ERT, BCVA in the treated eye was 0.2 with bull's eye maculopathy sparing outer retinal layers, whereas the untreated eye had progressed to endstage retinopathy and BCVA &lt;0.02. No intraocular side effects occurred.<\/jats:p><jats:p>Our results provide further evidence that IVT-ERT appears to be safe and markedly delays retinal degeneration preserving visual function and increasing the patient's quality of life, especially if started early.<\/jats:p>","DOI":"10.1055\/a-2510-5592","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T00:13:33Z","timestamp":1736295213000},"page":"142-146","source":"Crossref","is-referenced-by-count":5,"title":["Intravitreal Enzyme Replacement Therapy Slows Retinopathy in Late Infantile Ceroid Lipofuscinosis Type 2"],"prefix":"10.1055","volume":"56","author":[{"given":"Claudia S.","family":"Priglinger","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, LMU University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Courage","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelie S.","family":"Lotz-Havla","sequence":"additional","affiliation":[{"name":"Department of Inborn Errors of Metabolism, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Gerhardt","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, LMU University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Ehrt","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, LMU University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Kurz","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, LMU University Hospital, Ludwig-Maximilians-University Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Pudritz","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, LMU University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcnther","family":"Rudolph","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, LMU University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher B.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther M.","family":"Maier","sequence":"additional","affiliation":[{"name":"Department of Inborn Errors of Metabolism, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Munich, Germany"},{"name":"Labor Becker MVZ GbR, Newborn Screening Unit, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,1,21]]},"reference":[{"issue":"11","key":"ref1","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1016\/j.bbadis.2013.04.008","article-title":"NCL diseases\u2014clinical perspectives","volume":"1832","author":"A Schulz","year":"2013","journal-title":"Biochim Biophys Acta"},{"issue":"04","key":"ref2","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1002\/ajmg.10660","article-title":"Late infantile neuronal ceroid lipofuscinosis: quantitative description of the clinical course in patients with CLN2 mutations","volume":"112","author":"R Steinfeld","year":"2002","journal-title":"Am J Med Genet"},{"issue":"01","key":"ref3","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1186\/s13023-021-01858-6","article-title":"Presymptomatic treatment of classic late-infantile neuronal ceroid lipofuscinosis with cerliponase alfa","volume":"16","author":"J Schaefers","year":"2021","journal-title":"Orphanet J Rare Dis"},{"issue":"08","key":"ref4","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/S2352-4642(18)30179-2","article-title":"Disease characteristics and progression in patients with late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease: an observational cohort study","volume":"2","author":"M Nickel","year":"2018","journal-title":"Lancet Child Adolesc Health"},{"issue":"04","key":"ref5","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1111\/dmcn.14346","article-title":"Paediatric-onset neuronal ceroid lipofuscinosis: first symptoms and presentation at diagnosis","volume":"62","author":"B Dozi\u00e8res-Puyravel","year":"2020","journal-title":"Dev Med Child Neurol"},{"issue":"07","key":"ref6","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.oret.2020.01.011","article-title":"Symmetric age association of retinal degeneration in patients with CLN2-associated Batten disease","volume":"4","author":"K D Kovacs","year":"2020","journal-title":"Ophthalmol Retina"},{"issue":"08","key":"ref7","doi-asserted-by":"crossref","first-page":"e73128","DOI":"10.1371\/journal.pone.0073128","article-title":"Spectrum of ocular manifestations in CLN2-associated batten (Jansky-Bielschowsky) disease correlate with advancing age and deteriorating neurological function","volume":"8","author":"A Orlin","year":"2013","journal-title":"PLoS One"},{"issue":"20","key":"ref8","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1056\/NEJMoa1712649","article-title":"Study of intraventricular cerliponase alfa for CLN2 disease","volume":"378","author":"A Schulz","year":"2018","journal-title":"N Engl J Med"},{"issue":"01","key":"ref9","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/S1474-4422(23)00384-8","article-title":"Safety and efficacy of cerliponase alfa in children with neuronal ceroid lipofuscinosis type 2 (CLN2 disease): an open-label extension study","volume":"23","author":"A Schulz","year":"2024","journal-title":"Lancet Neurol"},{"issue":"09","key":"ref10","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1038\/s41433-021-01594-y","article-title":"An ERG and OCT study of neuronal ceroid lipofuscinosis CLN2 Battens retinopathy","volume":"35","author":"D A Thompson","year":"2021","journal-title":"Eye (Lond)"},{"issue":"10","key":"ref11","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1136\/bjo-2022-321260","article-title":"Ongoing retinal degeneration despite intraventricular enzyme replacement therapy with cerliponase alfa in late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2 disease)","volume":"107","author":"S Dulz","year":"2023","journal-title":"Br J Ophthalmol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"108130","DOI":"10.1016\/j.exer.2020.108130","article-title":"Intravitreal enzyme replacement preserves retinal structure and function in canine CLN2 neuronal ceroid lipofuscinosis","volume":"197","author":"R EH Whiting","year":"2020","journal-title":"Exp Eye Res"},{"issue":"06","key":"ref13","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1038\/s41433-023-02859-4","article-title":"First in man study of intravitreal tripeptidyl peptidase 1 for CLN2 retinopathy","volume":"38","author":"J Wawrzynski","year":"2024","journal-title":"Eye (Lond)"},{"issue":"03","key":"ref14","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1097\/ICU.0000000000001029","article-title":"Intravitreal enzyme replacement for inherited retinal diseases","volume":"35","author":"A C Rodriguez-Martinez","year":"2024","journal-title":"Curr Opin Ophthalmol"},{"issue":"01","key":"ref15","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s10633-021-09825-z","article-title":"Evolution of the retinal function by flash-ERG in one child suffering from neuronal ceroid lipofuscinosis CLN2 treated with cerliponase alpha: case report","volume":"143","author":"F Rigaudi\u00e8re","year":"2021","journal-title":"Doc Ophthalmol"}],"container-title":["Neuropediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2510-5592.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T23:41:34Z","timestamp":1741390894000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2510-5592"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,7]]},"references-count":15,"journal-issue":{"issue":"02","published-online":{"date-parts":[[2025,3,7]]},"published-print":{"date-parts":[[2025,4]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2510-5592","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0174-304X","1439-1899"],"issn-type":[{"value":"0174-304X","type":"print"},{"value":"1439-1899","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,1,7]]},"published":{"date-parts":[[2025,1,7]]}}}