OCT Biomarkers in Ocular CLN2 Disease in Patients Treated With Intraventricular Enzyme Replacement Therapy

TY - JOUR

T1 - OCT Biomarkers in Ocular CLN2 Disease in Patients Treated With Intraventricular Enzyme Replacement Therapy

AU - Huang, Wei Chieh

AU - Ohnsman, Christina M

AU - Atiskova, Yevgeniya

AU - Falabella, Paulo

AU - Spitzer, Martin S

AU - Schulz, Angela

AU - Dulz, Simon

PY - 2024/7/1

Y1 - 2024/7/1

N2 - PURPOSE: Bilateral progressive, symmetrical loss of central retinal thickness (CRT) has been described in neuronal ceroid lipofuscinosis type 2 (CLN2) disease. This study details the pattern of morphological changes underlying CRT loss and disease progression in patients receiving intracerebroventricular (ICV) enzyme replacement therapy (ERT) with cerliponase alfa.METHODS: Spectral-domain optical coherence tomography macular cube scans were collected from 16 patients with classic CLN2 disease receiving ICV ERT. Detailed retinal structure analyses were performed on manually segmented horizontal B-scans through the fovea to determine the thickness of six retinal parameters and the extent of ellipsoid zone (EZ) loss.RESULTS: Anatomical changes primarily occurred in photoreceptor (PR)-related retinal parameters and correlated with ocular disease severity. Retinal degeneration began with initial focal parafoveal EZ discontinuities signaling the onset of rapid PR degeneration in a predictable pattern: parafoveal PR involvement with foveal sparing followed by profound parafoveal and foveal PR loss with additional thinning beyond the central retina. PR degeneration began with outer segment loss and progressed to outer nuclear layer (ONL) involvement. Longitudinal analyses confirmed these observations. The rate of PR loss was fastest at the fovea at ∼58 mm per year and became slower at locations farther away from the fovea.CONCLUSIONS: Retinal degeneration in CLN2 disease is primarily associated with PR loss in a predictable pattern, with EZ disruption signaling early PR stress. CRT, ONL thickness, and PR layer thickness are useful anatomical biomarkers for understanding disease progression and treatment efficacy in CLN2. Studies using en face images will further clarify CLN2-related retinal degeneration.

AB - PURPOSE: Bilateral progressive, symmetrical loss of central retinal thickness (CRT) has been described in neuronal ceroid lipofuscinosis type 2 (CLN2) disease. This study details the pattern of morphological changes underlying CRT loss and disease progression in patients receiving intracerebroventricular (ICV) enzyme replacement therapy (ERT) with cerliponase alfa.METHODS: Spectral-domain optical coherence tomography macular cube scans were collected from 16 patients with classic CLN2 disease receiving ICV ERT. Detailed retinal structure analyses were performed on manually segmented horizontal B-scans through the fovea to determine the thickness of six retinal parameters and the extent of ellipsoid zone (EZ) loss.RESULTS: Anatomical changes primarily occurred in photoreceptor (PR)-related retinal parameters and correlated with ocular disease severity. Retinal degeneration began with initial focal parafoveal EZ discontinuities signaling the onset of rapid PR degeneration in a predictable pattern: parafoveal PR involvement with foveal sparing followed by profound parafoveal and foveal PR loss with additional thinning beyond the central retina. PR degeneration began with outer segment loss and progressed to outer nuclear layer (ONL) involvement. Longitudinal analyses confirmed these observations. The rate of PR loss was fastest at the fovea at ∼58 mm per year and became slower at locations farther away from the fovea.CONCLUSIONS: Retinal degeneration in CLN2 disease is primarily associated with PR loss in a predictable pattern, with EZ disruption signaling early PR stress. CRT, ONL thickness, and PR layer thickness are useful anatomical biomarkers for understanding disease progression and treatment efficacy in CLN2. Studies using en face images will further clarify CLN2-related retinal degeneration.

KW - Humans

KW - Tomography, Optical Coherence/methods

KW - Enzyme Replacement Therapy/methods

KW - Neuronal Ceroid-Lipofuscinoses/drug therapy

KW - Male

KW - Female

KW - Child

KW - Adolescent

KW - Biomarkers/metabolism

KW - Adult

KW - Young Adult

KW - Retina/diagnostic imaging

KW - Visual Acuity/physiology

KW - Disease Progression

KW - Child, Preschool

KW - Dipeptidyl-Peptidases and Tripeptidyl-Peptidases

KW - Recombinant Proteins

U2 - 10.1167/iovs.65.8.45

DO - 10.1167/iovs.65.8.45

M3 - SCORING: Journal article

C2 - 39078732

VL - 65

SP - 45

JO - INVEST OPHTH VIS SCI

JF - INVEST OPHTH VIS SCI

SN - 0146-0404

IS - 8

ER -