Purpose: Mutations in the CLN2 gene lead to a neurodegenerative and blinding lysosomal storage disorder: late infantile neuronal ceroid lipofucinosis, also known as “CLN2 disease.” The purpose of the current study was to characterize the evolution of CLN2-associated retinal manifestations using the Weill Cornell Batten Scale (WCBS) and the age association of the retinal degeneration using central subfield thickness (CST) measurements and then correlate these findings with fundus photography and OCT to determine a critical period for retinal intervention. Design: Retrospective, single-center cohort. Participants: Eighty-four eyes of 42 treatment-naïve patients with CLN2 disease. Methods: Clinical records, fundus photographs, and OCT imaging for patients with CLN2 disease collected during examinations under anesthesia were reviewed. Imaging was categorized per WCBS criteria by 3 masked graders. Main Outcome Measures: CLN2-associated retinopathy assessed using WCBS scores, fundus photographs, and OCT imaging, correlated with patient age. Results: Eighty-four eyes of 42 patients had baseline fundus photographs, with baseline OCT in 31 eyes of 16 patients. Fundus photographs were obtained serially for 26 eyes of 13 patients, and serial OCT scans were obtained in 10 eyes of 5 patients. At baseline, bilateral WCBS scores were highly correlated for OCT and fundus photographs (r = 0.96 and 0.82, respectively). Central subfield thickness was negatively correlated with left and right eye WCBS OCT scores (r = −0.92 and −0.83, respectively; P < 0.001) and fundus photograph scores (r = −0.80 and −0.83, respectively; P < 0.001). OCT thickness was symmetrical between each eye. Baseline OCT data with age fit using a sigmoid function demonstrated a period of accelerated loss between 48 and 72 months of age. Conclusions: Retinal degeneration associated with CLN2 disease manifests as a progressive, symmetrical decline, which appears to accelerate during a critical period at 48 to 72 months of age, suggesting intervention with retina-specific CLN2 gene therapy should occur ideally before or as early as possible within this critical period. The WCBS is a valuable tool and is highly correlated with the extent of retinal degeneration observed in OCT or fundus photographs; by using the fellow eye as a control, this grading scale can be used to monitor the effect of CLN2 gene therapy in future trials.
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