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Ongoing retinal degeneration despite intraventricular enzyme replacement therapy with cerliponase alfa in late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2 disease)
  1. Simon Dulz1,
  2. C Schwering2,
  3. Jan Wildner1,
  4. Christoph Spartalis1,
  5. Frank Schuettauf1,
  6. Udo Bartsch1,
  7. Eva Wibbeler2,
  8. Miriam Nickel2,
  9. Martin Stephan Spitzer1,
  10. Yevgeniya Atiskova1,
  11. Angela Schulz2
  1. 1 Department of Ophthalmology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  2. 2 Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  1. Correspondence to Dr Simon Dulz, Department of Ophthalmology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; s.dulz{at}uke.de

Abstract

Background/aims Late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) is a neurodegenerative, blinding lysosomal storage disorder. The purpose of the current study was to characterise the progression of CLN2-associated retinal degeneration in patients under intraventricular enzyme replacement therapy (ERT) with cerliponase alfa.

Methods We analysed visual function, retinal morphology and neuropaediatric data using preferential looking test (PLT), Weill Cornell Batten Scale (WCBS), optical coherence tomography (OCT) imaging and the Hamburg Motor-Language late-infantile neuronal ceroid lipofuscinosis (LINCL) Scale (M-L scale).

Results Fifty-six eyes of 28 patients had baseline PLT, WCBS and OCT. 15 patients underwent serial examinations, resulting in a total of 132 OCT scans and WCBS results, 66 Hamburg M-L scores and 49 PLT results during a mean follow-up time of 18.2 months (range 5–40). A negative correlation (r=–0.69, p<0.001) was found between central retinal thickness (CRT) values and age at examination with a maximal annual decrease of 23 µm between 56 and 80 months of age. A significant correlation was observed between PLT results and the age at examination (r=0.46, p=0.001), the WCBS scores (r=0.62; p<0.001) and CRT values (r=–0.64; p<0.001). The M-L score correlated with the ocular measurements (CRT: r=0.58, p<0.001; WCBS r=−0.64, p<0.001; PLT score: r=−0.57, p<0.001).

Conclusion Despite intraventricular ERT, retinal degeneration progressed in patients with CLN2 and was particularly pronounced between 56 and 80 months of age. Retina-directed therapies should therefore be initiated before or as early as possible during the phase of rapid retinal degeneration. PLT and WCBS were identified as valuable outcome measures to monitor disease progression.

Trial registration number NCT04613089.

  • Retina
  • Genetics
  • Macula

Data availability statement

Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

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Footnotes

  • YA and AS contributed equally.

  • Contributors Design of the study: SD, YA and AS. Collection, management, analysis and interpretation of data: SD, CSc, CSp, EW, FS, AS, JW, MN and UB. Preparation, review and approval of the manuscript: SD, MN, YA, AS, UB, FS and MS. Final approval of the manuscript: SD, YA, UB, MS and AS. SD is the guarantor.

  • Funding The research leading to these results has received funding from the German Federal Ministry of Education and Research (Grant NCL2Treat to AS) and by the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 66 691 (BATCure to AS). In addition, the work leading to this data collection was generously supported by fundraising by ‘Freundeskreis UKE für Kinder mit Demenz e.V.’.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.