Radial outer retina reflectivity ( RORR ) sign in LAMP2 ‐associated retinopathy
Year: 2026
Type: article
Study design: Observational Study
Abstract: PURPOSE: To describe the radial outer retina reflectivity (RORR) sign in patients carrying pathogenic variants in the X-linked lysosome-associated membrane protein-2 (LAMP2) gene and to review the histologic characteristics of LAMP2 expression in the human retina. METHODS: International multicentre observational case series and experimental laboratory study of patients with LAMP2 deficiency. Baseline demographics and multimodal retinal imaging including colour and fundus autofluorescence (FAF), optical coherence tomography (OCT) with en face reconstruction and fluorescein angiography were obtained. Sections through the retina of a human donor eye were processed for immunofluorescence combining antibodies against LAMP2 with markers for Müller glia, rod and cone photoreceptors. Sections were imaged using high-resolution multichannel confocal microscopy. Assessment of en face OCT reflectivity profiles at 5-50 μm internal to the plane of external limiting membrane (ELM) was performed as well as histologic localisation of LAMP2. RESULTS: We recruited 11 cases with pathogenic variants in LAMP2 across five countries. Six cases demonstrated peripheral radial streaks of hyper- and hypopigmentation with UWF imaging. The RORR sign was best visualised 10-25 μm internal to ELM in 9 cases. We hypothesise the radial pattern to be secondary to X-chromosome inactivation. LAMP2 immunoreactivity was observed internal and external to the ELM. CONCLUSION: Our findings expand the phenotypic spectrum of LAMP2-associated retinopathy by demonstrating the RORR sign using en face OCT. Histologic sections revealed LAMP2 expression in the neuroretina.
Source: Acta Ophthalmologica
DOI: 10.1111/aos.70178
Authors: Rachael C. Heath Jeffery, Bohdan Kousal, Ulrike Grünert, Christine A. Curcio, Svetlana Cherepanoff, Tina M. Lamey, Michel Michaelides, Chrysanthi Tsika, Isabelle Chow, Omar A. Mahroo, Seungmin Lee, Martin Meliska, Milos Kubanek, Jakub Sikora, Siying Lin, Raymond C. B. Wong, Petra Liskova, Fred K. Chen
Institutions: Lions Eye Institute, The University of Western Australia, The Royal Victorian Eye & Ear Hospital, Charles University, General University Hospital in Prague, The University of Sydney, University of Alabama at Birmingham, UAB Medicine, UNSW Sydney, St Vincent's Hospital Sydney, Sir Charles Gairdner Hospital, Moorfields Eye Hospital NHS Foundation Trust, University College London, St Thomas' Hospital, King's College London, University of Cambridge, Pusan National University Hospital, Institute of Clinical and Experimental Medicine, Manchester Academic Health Science Centre, University of Manchester, St Mary's Hospital, Manchester University NHS Foundation Trust, Centre for Eye Research Australia
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,990
OpenAlex ID: W7166558907