Analysis of imaging biomarkers and retinal nerve fiber layer thickness in RPGR-associated retinitis pigmentosa

Theresa H Birtel,Philipp Herrmann,Frank G Holz,Martin Gliem,Moritz Lindner,Kristina Hess,Amelie C Clemens,Johannes Birtel

doi:10.1007/s00417-021-05233-w

Abstract

PurposeTo investigate multimodal retinal imaging characteristics including the retinal nerve fiber layer (RNFL) thickness in patients with RPGR-associated retinitis pigmentosa (RP).MethodsThis cross-sectional case–control study included 17 consecutive patients (median age, 21 years) with RPGR-associated RP who underwent retinal imaging including optical coherence tomography (OCT), short-wavelength fundus autofluorescence (AF) imaging, and RNFL scans centered on the optic disc. RNFL thickness was manually segmented and compared to clinical and imaging parameters including the transfoveal ellipsoid zone (EZ) width, the horizontal diameter of the macular hyperautofluorescent ring. RNFL thickness was compared to 17 age- and sex-matched controls.ResultsIn patients with RPGR-associated RP, the EZ width (R2 = 0.65), the central hyperautofluorescent ring on AF images (R2 = 0.72), and visual acuity (R2 = 0.68) were negatively correlated with age. In comparison to controls, a significantly (p < 0.0001) increased global RNFL thickness was identified in RPGR-associated RP, which was, however, less pronounced in progressed disease as indicated by the EZ width or the diameter of the central hyperautofluorescent ring.ConclusionsThis study describes retinal characteristics in patients with RPGR-associated RP including a pronounced peripapillary RNFL thickness compared to healthy controls. These results contribute to the knowledge about imaging biomarkers in RP, which might be of interest for therapeutic approaches such as gene replacement therapies.

Highlights

Mutations in the RPGR gene are the major cause of X-linked retinitis pigmentosa (RP)
Our cross-sectional structural-functional approach of patients with RPGR-associated RP revealed that visual acuity, the ellipsoid zone (EZ) width, and the diameter of the hyperautofluorescent ring negatively correlated with age
The correlation between age and EZ width, with larger EZs in younger patients and a pronounced EZ decline in patients under the age of 20 years, is in accordance with previous reports identifying a faster rate of EZ decline in younger patients regardless of the underlying RPGR variant [22, 24]

Summary

Introduction

Mutations in the RPGR gene are the major cause of X-linked retinitis pigmentosa (RP). Graefe’s Archive for Clinical and Experimental Ophthalmology the third or fourth decade of life. It represents one of the most severe forms of RP in males [1,2,3,4,5,6,7,8,9]. It appears crucial to screen families with a provisional diagnosis of autosomal dominant or sporadic inheritance for variants in X-linked genes as well [15, 16]. With the development of novel treatment approaches for RPGR-associated RP, in particular gene replacement therapy, an explicit disease characterization including multimodal retinal imaging is increasingly important [17,18,19,20,21]. Previous natural history studies have shown an exponential decline of the ellipsoid zone (EZ) width and the hyperautofluorescent ring [22,23,24]

Methods

Results

Conclusion