Related Experiment Video
Updated: Sep 17, 2025
Intravitreal Injections in the Ovine Eye
Published on: July 5, 2022
Same-Day Approach for Combined Intravitreal and Intracerebroventricular Enzyme Replacement Therapy to Prevent Retinal
David L Rogers1, Jill E Blind2, Troy Kienzle2
1Department of Ophthalmology, Nationwide Children's Hospital, Columbus, Ohio; Department of Ophthalmology, The Ohio State University, Columbus, Ohio.
Insights
A new method allows same-day administration of intracerebroventricular and intravitreal cerliponase alfa for CLN2 patients. This combined treatment targets both brain and eye tissues to potentially slow vision loss in neuronal ceroid lipofuscinosis.
Area of Science:
- Neurology
- Ophthalmology
- Genetics
Background:
- Classic late infantile neuronal ceroid lipofuscinosis (CLN2) is a genetic disorder caused by TPP1 gene mutations.
- Patients experience progressive vision loss, leading to blindness, and motor function decline.
- Intracerebroventricular cerliponase alfa (Brineura) is approved to slow ambulation loss, but visual decline persists.
Purpose of the Study:
- To develop a streamlined protocol for simultaneous administration of intracerebroventricular and intravitreal cerliponase alfa.
- To establish a method for delivering cerliponase alfa directly to ocular tissues for CLN2 patients.
Main Methods:
- A novel preparation technique utilizing vial overfill enables same-day administration of both treatment routes.
- Intravitreal injections of cerliponase alfa (0.2 mg in 0.05 mL) are administered every 4 weeks under anesthesia using sterile techniques.
- Intracerebroventricular infusion follows standard protocols after the ocular procedure.
Main Results:
- The described pathway facilitates concurrent administration of both intracerebroventricular and intravitreal cerliponase alfa.
- The procedure involves sterile compounding and administration of intravitreal injections followed by intracerebroventricular infusion.
Conclusions:
- This combined administration pathway is adaptable for centers already providing intracerebroventricular cerliponase alfa.
- Centers with available ophthalmologic expertise can implement this protocol to potentially improve CLN2 treatment outcomes.
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.
