Abstract
Purpose :
Cone-rod degeneration is a prominent feature of neuronal ceroid lipofuscinosis Type 2 (CLN2) disease. While bilateral progressive, symmetrical loss of central retinal thickness (CRT) has been well-characterized, other OCT anatomical biomarkers have not been described in as much detail. This study was therefore undertaken to further explore progression of anatomical retinal changes in CLN2 disease.
Methods :
SD-OCT macular cube scans were collected in 31 subjects, ages 5 to 157 months, with classic CLN2 disease. Horizontal B-scans through the fovea from one eye per subject were segmented manually to determine thickness of six retinal parameters: full retinal thickness (FRT), retinal nerve fiber layer, inner nuclear layer, outer nuclear layer (ONL), photoreceptor (PR) plus retinal pigment epithelium (RPE), and outer segment plus RPE (OS+RPE). Ellipsoid zone (EZ) integrity was also examined. FRT was measured in standard Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. In addition to cross-sectional analysis, longitudinal data for individual patients were analyzed when available.
Results :
CRT loss correlated to disease severity and Weill Cornell Late Infantile Neuronal Ceroid Lipofuscinosis Severity Scores. A linear relationship between loss of CRT and foveal ONL thickness confirmed the connection between PR loss and disease progression. Retinal degeneration in the macula showed a predictable pattern on horizontal scans, with relative foveal sparing and parafoveal involvement in early disease, followed by more profound foveal degeneration with additional ONL thinning beyond the central retina later in the disease. Focal EZ changes in the macula were an early signal of PR degeneration, progressing to more extensive EZ loss in later stages. PR degeneration in OS+RPE preceded ONL loss. Marked FRT reduction was also observed in ETDRS para- and peri-central sectors in late stages. Analyses of longitudinal data confirmed these observations.
Conclusions :
CRT is a useful anatomical biomarker in CLN2 until maximal foveal thinning has occurred late in the disease, when para- and peri-central sector changes become more significant for understanding disease progression and treatment efficacy. Further studies using en face images will further clarify progression of retinal degeneration in CLN2 disease. Additional longitudinal data are needed to characterize the pattern and progression of EZ loss in CLN2 disease.
This is a 2021 ARVO Annual Meeting abstract.