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