Gocuk Sena Ayse, Hadoux Xavier, Catipon Charmaine, Cichello Elise, Kumar Himeesh, Jolly Jasleen Kaur, van Wijngaarden Peter, Llewelyn Edwards Thomas, Ayton Lauren Nicole, Sousa David Cordeiro
Department of Optometry and Vision Sciences, The University of Melbourne, Melbourne, VIC, Australia.
Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, VIC, Australia.
Front Ophthalmol (Lausanne). 2024 Jul 9;4:1415393. doi: 10.3389/fopht.2024.1415393. eCollection 2024.
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.
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.
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).
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.
X连锁遗传性视网膜疾病（IRD）的女性携带者可表现出高度可变的表型和疾病进展。血管反应性作为一种潜在的疾病生物标志物，尚未在女性IRD携带者中进行研究。在本研究中，功能性光学相干断层扫描血管造影（OCT-A）被用于动态评估X连锁IRD携带者的视网膜微血管系统。
招募经基因确诊的IRD（脉络膜视网膜炎或X连锁视网膜色素变性）女性携带者和健康女性。对15名X连锁IRD女性携带者的36只眼和21名年龄匹配的对照女性进行黄斑血管造影（3×3mm，蔡司Plex Elite 9000）。应用两项测试来检测血管反应性：（i）轻度缺氧和（ii）握力测试，分别诱导血管舒张或血管收缩反应。在每项测试期间，分别对浅表和深层毛细血管丛的血管密度（VD）和血管长度密度（VLD）变化进行独立评估。
在对照组中，握力测试期间浅表和深层VD均降低（分别为p<0.001和p=0.037）。握力测试期间平均浅表VLD也降低（p=0.025），而深层毛细血管丛无显著变化（p=0.108）。在缺氧期间，深层毛细血管丛的VD和VLD增加（分别为p=0.027和p=0.052），而浅表毛细血管丛未增加。在携带者中，两项测试期间任一毛细血管丛均未观察到对照组中出现的生理性血管反应，VD或VLD无差异（所有p>0.05）。
功能性OCT-A是评估视网膜微血管动态变化的有用工具。X连锁IRD携带者中所见生理性血管反应的亚临床损害可能是一种有价值的临床生物标志物。
