Morphological and functional parameters in X-linked retinoschisis patients-A multicentre retrospective cohort study

Peter Kiraly; Immanuel P Seitz; Maram E A Abdalla Elsayed; Susan M Downes; Chetan K Patel; Peter Charbel Issa; Johannes Birtel; Luca Mautone; Simon Dulz; Yevgeniya Atiskova; Philipp Herrmann; Nika Vrabič; Martina Jarc-Vidmar; Marko Hawlina; M Dominik Fischer

doi:10.3389/fmed.2023.1331889

Morphological and functional parameters in X-linked retinoschisis patients-A multicentre retrospective cohort study

Front Med (Lausanne). 2024 Jan 11:10:1331889. doi: 10.3389/fmed.2023.1331889. eCollection 2023.

Authors

Peter Kiraly^{1

2}, Immanuel P Seitz³, Maram E A Abdalla Elsayed¹, Susan M Downes^{1

2}, Chetan K Patel¹, Peter Charbel Issa^{1

2}, Johannes Birtel^{1

2

4

5}, Luca Mautone⁴, Simon Dulz⁴, Yevgeniya Atiskova⁴, Philipp Herrmann⁵, Nika Vrabič⁶, Martina Jarc-Vidmar⁶, Marko Hawlina⁶, M Dominik Fischer^{1

2

3}

Affiliations

¹ Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
² Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, United Kingdom.
³ Centre for Ophthalmology, University Hospital Tübingen, Tübingen, Germany.
⁴ Department of Ophthalmology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁵ Department of Ophthalmology, University Hospital Bonn, Bonn, Germany.
⁶ Eye Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.

Abstract

Introduction: X-linked retinoschisis (XLRS) is a potential target for gene supplementation approaches. To establish potential structural and functional endpoints for clinical trials, a comprehensive understanding of the inter-eye symmetry, relationship between structural and functional parameters, and disease progression is vital.

Methods: In this retrospective multicentre study, 118 eyes of 59 XLRS patients with RS1 mutations were assessed. Information from center databases included: RS1 variant; age at presentation; best-corrected visual acuity (BCVA), central retinal thickness (CRT), macular volume (MV) at presentation and at the last follow up; full-field electroretinogram (ERG) findings; presence of peripheral retinoschisis and complications (vitreous hemorrhage, retinal detachment); treatment with systemic or topical carbonic anhydrase inhibitors (CAI).

Results: Inter-eye symmetry revealed strong correlation in CRT (r = 0.77; p < 0.0001) and moderate correlations in MV (r = 0.51, p < 0.0001) and BCVA (r = 0.49; p < 0.0001). Weak or no correlations were observed between BCVA and structural parameters (CRT, MV). Peripheral retinoschisis was observed in 40 (68%), retinal detachment in 9 (15%), and vitreous hemorrhage in 5 (8%) patients, respectively. Longitudinal examinations (mean, 4.3 years) showed no BCVA changes; however, a reduction of the CRT (p = 0.02), and MV (p = 0.01) was observed. Oral and/or topical CAI treatment did not significantly alter the CRT (p = 0.34).

Discussion: The XLRS phenotype demonstrates a strong CRT symmetry between the eyes within individual patients and stable BCVA over several years. BCVA exhibits a weak correlation with the morphological parameters of retinal thickness (CRT MV). In our cohort, longitudinal functional changes were not significant, likely attributed to the short average follow-up period. Furthermore, CAI treatment didn't influence both morphological and functional outcomes.

Keywords: X-linked retinoschisis; XLRS; carbonic anhydrase inhibitors; functional parameters; gene therapy; morphological parameters; symmetry between eyes; trial endpoints.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Institute for Health and Care Research (NIHR) grant: BRC4 Gene and Cell Therapy.