Radial outer retina reflectivity ( <scp>RORR</scp> ) sign in <scp> <i>LAMP2</i> </scp> ‐associated retinopathy

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.

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Journal
Acta Ophthalmologica
Published
2026-06-28
DOI
https://doi.org/10.1111/aos.70178
Primary Topic
Retinal Development and Disorders
Type
article
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article

Radial outer retina reflectivity ( RORR ) sign in LAMP2 ‐associated retinopathy

Isabelle Chow, Rachael C. Heath Jeffery, Siying Lin, Raymond C.B. Wong et al.
Acta Ophthalmologica
Retinal Development and Disorders
article

Radial outer retina reflectivity ( RORR ) sign in LAMP2 ‐associated retinopathy

Isabelle Chow, Rachael C. Heath Jeffery, Siying Lin, Raymond C.B. Wong, Petra Lišková, Ulrike Grünert, Martin Meliska, Fred K. Chen, Jakub Sikora, Svetlana Cherepanoff, Chrysanthi Tsika, Bohdan Kousal, Seung Min Lee, Milos Kubanek, Christine A. Curcio, Omar A. Mahroo, Tina M. Lamey, Michel Michaelides
article en

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.

Acta Ophthalmologica
Lions Eye Institute (AU), University College Hospital (GB), St Thomas' Hospital (GB), Moorfields Eye Hospital NHS Foundation Trust (GB), The University of Western Australia (AU), Charles University (CZ), University of Cambridge (GB), Manchester Academic Health Science Centre (GB), Sir Charles Gairdner Hospital (AU), University of Manchester (GB), University of Alabama at Birmingham (US), St Vincent's Hospital Sydney (AU), The Royal Victorian Eye & Ear Hospital (AU), Centre for Eye Research Australia (AU), St Mary's Hospital (GB), St Vincent's Clinic (AU), Institute of Clinical and Experimental Medicine (CZ), Sextures Institute (AU), Ingham Institute (AU), Moorfields Eye Hospital (GB), General University Hospital in Prague (CZ), University College London (GB), Pusan National University (KR)
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Retinal Development and Disorders
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