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

Background

Classic late infantile neuronal ceroid lipofuscinosis (CLN2) is caused by a biallelic mutations of the TPP1 gene. Vision loss begins around age four years, resulting in blindness by age seven to ten 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.