Retinal vascular reactivity in carriers of X-linked inherited retinal disease - a study using optical coherence tomography angiography

Sena Ayse Gocuk; Xavier Hadoux; Charmaine Catipon; Elise Cichello; Himeesh Kumar; Jasleen Kaur Jolly; Peter van Wijngaarden; Thomas Llewelyn Edwards; Lauren Nicole Ayton; David Cordeiro Sousa

doi:10.3389/fopht.2024.1415393

Retinal vascular reactivity in carriers of X-linked inherited retinal disease - a study using optical coherence tomography angiography

Front Ophthalmol (Lausanne). 2024 Jul 9:4:1415393. doi: 10.3389/fopht.2024.1415393. eCollection 2024.

Authors

Sena Ayse Gocuk^{1

2

3}, Xavier Hadoux^{2

3}, Charmaine Catipon², Elise Cichello², Himeesh Kumar^{2

3}, Jasleen Kaur Jolly⁴, Peter van Wijngaarden^{2

3}, Thomas Llewelyn Edwards^{2

3}, Lauren Nicole Ayton^{1

2

3}, David Cordeiro Sousa^{2

3}

Affiliations

¹ Department of Optometry and Vision Sciences, The University of Melbourne, Melbourne, VIC, Australia.
² Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, VIC, Australia.
³ Ophthalmology, Department of Surgery, The University of Melbourne, Melbourne, VIC, Australia.
⁴ Vision and Eye Research Institute, Anglia Ruskin University, Cambridge, United Kingdom.

Abstract

Purpose: Female carriers of X-linked inherited retinal diseases (IRDs) can show highly variable phenotypes and disease progression. Vascular reactivity, a potential disease biomarker, has not been investigated in female IRD carriers. In this study, functional optical coherence tomography angiography (OCT-A) was used to dynamically assess the retinal microvasculature of X-linked IRD carriers.

Methods: Genetically confirmed female carriers of IRDs (choroideremia or X-linked retinitis pigmentosa), and healthy women were recruited. Macular angiograms (3x3mm, Zeiss Plex Elite 9000) were obtained in 36 eyes of 15 X-linked IRD female carriers and 21 age-matched control women. Two tests were applied to test vascular reactivity: (i) mild hypoxia and (ii) handgrip test, to induce a vasodilatory or vasoconstrictive response, respectively. Changes to vessel density (VD) and vessel length density (VLD) were independently evaluated during each of the tests for both the superficial and deep capillary plexuses.

Results: In the control group, the superficial and deep VD decreased during the handgrip test (p<0.001 and p=0.037, respectively). Mean superficial VLD also decreased during the handgrip test (p=0.025), while the deep plexus did not change significantly (p=0.108). During hypoxia, VD and VLD increased in the deep plexus (p=0.027 and p=0.052, respectively) but not in the superficial plexus. In carriers, the physiologic vascular responses seen in controls were not observed in either plexus during either test, with no difference in VD or VLD noted (all p>0.05).

Conclusions: Functional OCT-A is a useful tool to assess dynamic retinal microvascular changes. Subclinical impairment of the physiological vascular responses seen in carriers of X-linked IRDs may serve as a valuable clinical biomarker.

Keywords: OCT-A; X-linked; carrier; females; inherited retinal disease; retinal vasculature.

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 Australian Government Research Training Program Scholarship and the ARVO 2023 International Travel Grant awarded to SG; a University of Melbourne Driving Research Momentum Fellowship to LA; and an NHMRC Investigator grant to LA (GNT#1195713). Centre for Eye Research Australia receives support from the Victorian State Government through its Operational Infrastructure Support Program. JJ and LA are on the scientific advisory board for the Choroideremia Research Foundation. JJ was supported by a National Institute for Health and Social Care Fellowship (NIHR). The sponsor and funding organization had no role in the design or conduct of this research.