Abstracts

Rationale: Cortical visual impairment (CVI) is commonly described in patients with CDKL5 deficiency disorder (CDD) but not well characterized. We aimed to characterize the ophthalmological phenotype of CDD and assess the potential for visual acuity (VA) to serve as a biomarker. Methods: We retrospectively analyzed clinical data from patients with CDD at Boston Children’s Hospital. Patients with structural eye abnormalities or visual pathway abnormalities on MRI were excluded. We studied complete ophthalmological assessments including evaluation of VA by preferential looking (PL) method and by sweep visual evoked potential (sVEP) and the trajectories over time. Results: We identified 26 patients with CDD who met criteria for the study, 85% female, age 3 months to 16.5 years. Ophthalmological exams documented nystagmus in 28% and strabismus in 77% of patients. Twenty-four patients had VA measured by PL and 13 by both PL and sVEP. VAs were lower than age expectations but demonstrated improvement in the first 3 years. Adjusting for age of visual maturity and sex, best PL VA after 2 years of age was 5.1 cycles per degree higher in individuals with mobility compared to those who were non-mobile. Conclusions: In a cohort of patients with CDD, all of whom were diagnosed with CVI, we demonstrated that VA can be assessed by PL and sVEP methods. We observed longitudinal improvement and correlation with mobility status. VA thus represents a dynamic and quantifiable biomarker in CDD and as such should be considered as an outcome measure in pre-clinical studies and clinical trials. Funding: National Institute of Neurologic Disorders and Stroke (K23 NS107646-01) The International Foundation for CDKL5 Research