Department of Ophthalmology, University of Erlangen-Nürnberg, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, Germany.
Max Delbrück Center for Molecular Medicine, Berlin, Germany.
PLoS One. 2021 May 7;16(5):e0249202. doi: 10.1371/journal.pone.0249202. eCollection 2021.
Agonistic β2-adrenergic receptor autoantibodies (β2-agAAb) have been observed in sera of patients with ocular hypertension and open-angle glaucoma (OAG). They target the β2-receptors on trabecular meshwork, ciliary body and pericytes (Junemann et al. 2018; Hohberger et al. 2019). In addition to their influence on the intraocular pressure, an association to retinal microcirculation is discussed. This study aimed to investigate foveal avascular zone (FAZ) characteristics by en face OCT angiography (OCT-A) in glaucoma suspects and its relationship to β2-agAAb status in patients with OAG.
Thirty-four patients (28 OAG, 6 glaucoma suspects) underwent standardized, clinical examination including sensory testing as white-on-white perimetry (Octopus G1, mean defect, MD) and structural measures as retinal nerve fibre layer (RNFL) thickness, neuroretinal rim width (BMO-MRW), retinal ganglion cell layer (RGCL) thickness, and inner nuclear layer (INL) thickness with high-resolution OCT. FAZ characteristics were measured by OCT-A scans of superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). FAZ-R was calculated (area FAZ (SVP)/area FAZ (ICP)). Using cardiomyocyte bioassays we analysed serum samples for the presence of β2-agAAb.
(I) Total mean FAZ area [mm2]: 0.34±0.16 (SVP), 0.24±0.12 (ICP), and 0.49±0.24 (DCP); mean FAZ-R 1.58±0.94. No correlation was seen for FAZ-R with MD, RNFL, BMO-MRW, RGCL thickness and INL thickness (p>0.05). (II) ß2-agAAb have been observed in 91% patients and showed no correlation with MD, RNFL, BMO-MRW, RGCL thickness and INL thickness (p>0.05). (III) FAZ-R correlated significantly with the β2-agAAb-induced increase of the beat rate of cardiomyocyte (p = 0.028).
FAZ characteristics did not correlate with any glaucoma associated functional and morphometric follow-up parameter in the present cohort. However, level of β2-agAAb showed a significantly correlation with FAZ-ratio. We conclude that β2-agAAb might be a novel biomarker in glaucoma pathogenesis showing association to FAZ-ratio with OCT-A.
已在眼高压和开角型青光眼（OAG）患者的血清中观察到激动β2-肾上腺素能受体自身抗体（β2-agAAb）。它们靶向小梁网，睫状体和周细胞上的β2-受体（Junemann 等人，2018 年；Hohberger 等人，2019 年）。除了对眼内压的影响外，还讨论了与视网膜微循环的关联。本研究旨在通过青光眼疑似患者的眼前节 OCT 血管造影（OCT-A）研究黄斑无血管区（FAZ）特征，并研究其与 OAG 患者β2-agAAb 状态的关系。
34 名患者（28 名 OAG，6 名青光眼疑似患者）接受了标准化的临床检查，包括作为白对白视野计的感觉测试（Octopus G1，平均缺损，MD）和作为视网膜神经纤维层（RNFL）厚度、神经视网膜边缘宽度（BMO-MRW）、视网膜神经节细胞层（RGCL）厚度和内层核层（INL）厚度的结构测量（高分辨率 OCT）。通过浅层血管丛（SVP），中间毛细血管丛（ICP）和深层毛细血管丛（DCP）的 OCT-A 扫描测量 FAZ 特征。计算 FAZ-R（FAZ（SVP）/FAZ（ICP）面积）。使用心肌细胞生物测定法，我们分析了血清样本中β2-agAAb 的存在。
（I）总平均 FAZ 面积[mm2]：SVP 为 0.34±0.16，ICP 为 0.24±0.12，DCP 为 0.49±0.24；FAZ-R 为 1.58±0.94。FAZ-R 与 MD，RNFL，BMO-MRW，RGCL 厚度和 INL 厚度之间没有相关性（p>0.05）。（II）β2-agAAb 在 91%的患者中被观察到，与 MD，RNFL，BMO-MRW，RGCL 厚度和 INL 厚度无相关性（p>0.05）。（III）FAZ-R 与心肌细胞搏动率的β2-agAAb 诱导增加呈显著相关（p = 0.028）。
在本研究队列中，FAZ 特征与任何与青光眼相关的功能和形态学随访参数均无相关性。然而，β2-agAAb 的水平与 FAZ 比呈显著相关性。我们得出的结论是，β2-agAAb 可能是青光眼发病机制中的一种新型生物标志物，与 OCT-A 显示的 FAZ 比有关。
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