Poster Presentation International Congress on Neuronal Ceroid Lipofuscinoses 2025

Same-Day Approach for Combined Intravitreal and Intracerebroventricular Enzyme Replacement Therapy to Prevent Retinal Disease Progression in Children with Neuronal Ceroid Lipofuscinosis Type 2 (#29)

Catherine O Jordan 1 , Jill E Blind 1 , Troy Troy 1 , Emily De Los Reyes 1 , Thomas A. Mendel 2 , David L Rogers 1
  1. Nationwide Children's Hospital, Columbus, OHIO, United States
  2. Ophthalmology, The Ohio State University , Columbus, Ohio, United States

Background: Classic late infantile neuronal ceroid lipofuscinosis (CLN2) is caused by a biallelic mutations of the TPP1 gene. Vision loss begins around age four 4 years, resulting in blindness by age 7-10 years. Intracerebroventricular cerliponase alfa (Brineura, BioMarin) is indicated to slow the loss of ambulation in pediatric patients with CLN2. However, treated children continue to experience visual loss. Intravitreal cerliponase alfa allows the enzyme to target tissues in the eye, offering a treatment option.

Methods: We developed a pathway for same-day administration of both intravitreal and intracerebroventricular cerliponase alfa using a preparation technique that takes advantage of the overfill in the vial.

Results: The intravitreal injection of cerliponase alfa is given every 4 weeks. The patient arrives and is registered for both procedures. Sterile technique is used to compound the intracerebroventricular infusion and the intravitreal injections. The intravitreal injection is performed under anesthesia using sterile technique in each eye. The dose of cerliponase alfa injected is 0.2 mg diluted in 0.05 mL of artificial cerebrospinal fluid. The intracerebroventricular infusion is then administered per standard protocol in the infusion center. 

Conclusions: We believe our pathway can be applied at all centers that are currently administering intracerebroventricular cerliponase alfa and that have the ophthalmologic expertise available to administer intravitreal injections.

  1. S. Dulz, C. Schwering, J. Wildner, et al. Ongoing retinal degeneration despite intraventricular enzyme replacement therapy with cerliponase alfa in late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2 disease) Br J Ophthalmol, 107 (10) (2023), pp. 1478-1483
  2. J. Wawrzynski, P. Gissen, R. Bowman, R. Bower, C. Gan, L. Harding, et al. Intravitreal Cerliponase alfa for the treatment of CLN2 type Batten Disease related retinal dystrophy: A first in man report of ocular enzyme replacement Invest. Ophthalmol. Vis. Sci, 63 (7) (2022), p. 1109
  3. Rogers DL, De los Reyes EC, Mendel TA, Caprul BJ, Podlasiak S, Jordan CO. Intravitreal enzyme replacement therapy to prevent retinal disease progression in children with neuronal ceroid lipofuscinosis type 2 (CLN2): 3-year Safety and Efficacy Outcomes. Presented as an oral presentation at the 2025 Annual Meeting of AAPOS, Salt Lake City, UT.
  4. A.C. Rodriguez-Martinez, J. Wawrzynski, R.H. Henderson Intravitreal enzyme replacement for inherited retinal diseases Curr Opin Ophthalmol, 35 (3) (2024 May 1), pp. 232-237