PDF(Pubmed)
Abstract：
UNASSIGNED: The purpose of this study was to investigate the genotypic and phenotypic characteristics of CRB1-associated early onset retinal dystrophy (CRB1-eoRD) and retinal architecture by swept-source optical coherence tomography (SS-OCT).
UNASSIGNED: Eleven probands with CRB1-eoRD were recruited. Clinical information, genetic analysis, and comprehensive ophthalmic examinations including SS-OCT and SS-OCT angiography (SS-OCTA) were conducted.
UNASSIGNED: A total of 81.8% (9/11) of CRB1-eoRD presented as Leber congenital amaurosis (LCA). Common clinical manifestations included coin-like yellow-white retinal spots (20/22, 90.9%) and para-arteriolar retinal pigment epithelial retention (12/22, 54.5%). Nineteen different CRB1 variants were detected in our case series, including 12 missense, 3 frameshifts, 3 nonsense, and 1 splicing. Of them, 12 variants had been reported, and 7 were novel. SS-OCT showed thinner central macula (the LCA group, P < 0.0001), thicker total retina (P < 0.0001), thinner outer retina (P < 0.05), and thicker inner retina (P < 0.0001) compared with the healthy control. The inner/outer (I/O) retina thickness ratio of CRB1-eoRD was 3.0, higher than the healthy control of 1.2 and other inherited retinal diseases (IRDs) of 2.2 (P < 0.0001 and P = 0.0027, respectively). SS-OCTA revealed an increased vascular density and perfusion area of the superficial vascular complex and deep vascular complex in CRB1-eoRD.
UNASSIGNED: LCA emerges as a frequently occurring phenotype in CRB1-eoRD. The unique features of SS-OCT and SS-OCTA are illustrated, and the novel biomarker, I/O ratio, may facilitate early diagnosis. The insights gained from this study hold significant value in determining the treatment window for potential forthcoming CRB1 gene therapy.
UNASSIGNED: Eleven probands with CRB1-eoRD were recruited. Clinical information, genetic analysis, and comprehensive ophthalmic examinations including SS-OCT and SS-OCT angiography (SS-OCTA) were conducted.
UNASSIGNED: A total of 81.8% (9/11) of CRB1-eoRD presented as Leber congenital amaurosis (LCA). Common clinical manifestations included coin-like yellow-white retinal spots (20/22, 90.9%) and para-arteriolar retinal pigment epithelial retention (12/22, 54.5%). Nineteen different CRB1 variants were detected in our case series, including 12 missense, 3 frameshifts, 3 nonsense, and 1 splicing. Of them, 12 variants had been reported, and 7 were novel. SS-OCT showed thinner central macula (the LCA group, P < 0.0001), thicker total retina (P < 0.0001), thinner outer retina (P < 0.05), and thicker inner retina (P < 0.0001) compared with the healthy control. The inner/outer (I/O) retina thickness ratio of CRB1-eoRD was 3.0, higher than the healthy control of 1.2 and other inherited retinal diseases (IRDs) of 2.2 (P < 0.0001 and P = 0.0027, respectively). SS-OCTA revealed an increased vascular density and perfusion area of the superficial vascular complex and deep vascular complex in CRB1-eoRD.
UNASSIGNED: LCA emerges as a frequently occurring phenotype in CRB1-eoRD. The unique features of SS-OCT and SS-OCTA are illustrated, and the novel biomarker, I/O ratio, may facilitate early diagnosis. The insights gained from this study hold significant value in determining the treatment window for potential forthcoming CRB1 gene therapy.
摘要：
■本研究的目的是通过扫频源光学相干断层扫描（SS-OCT）研究CRB1相关的早发性视网膜营养不良（CRB1-eoRD）和视网膜结构的基因型和表型特征。
■招募了11名CRB1-eoRD先证者。临床信息,遗传分析,并进行了包括SS-OCT和SS-OCT血管造影(SS-OCTA)在内的全面眼科检查。
■共有81.8%(9/11)的CRB1-eoRD表现为Leber先天性黑蒙(LCA)。常见临床表现为硬币状黄白色视网膜斑点(20/22,90.9%)和小动脉旁视网膜色素上皮潴留(12/22,54.5%)。在我们的病例系列中检测到19种不同的CRB1变体，包括12个错觉，3移相台，3废话，和1个拼接。其中,已经报告了12种变体，7、小说SS-OCT显示中央黄斑变薄（LCA组，P<0.0001),总视网膜较厚（P<0.0001），较薄的外视网膜（P<0.05），与健康对照相比，内部视网膜较厚（P<0.0001）。CRB1-eoRD的内/外（I/O）视网膜厚度比为3.0，高于健康对照组的1.2和其他遗传性视网膜疾病（IRD）的2.2（分别为P<0.0001和P=0.0027）。SS-OCTA显示CRB1-eoRD中浅表血管复合体和深层血管复合体的血管密度和灌注面积增加。
■LCA是CRB1-eoRD中经常出现的表型。说明了SS-OCT和SS-OCTA的独特功能，和新的生物标志物，I/O比,有助于早期诊断。从这项研究中获得的见解在确定潜在的即将进行的CRB1基因治疗的治疗窗口方面具有重要价值。
■招募了11名CRB1-eoRD先证者。临床信息,遗传分析,并进行了包括SS-OCT和SS-OCT血管造影(SS-OCTA)在内的全面眼科检查。
■共有81.8%(9/11)的CRB1-eoRD表现为Leber先天性黑蒙(LCA)。常见临床表现为硬币状黄白色视网膜斑点(20/22,90.9%)和小动脉旁视网膜色素上皮潴留(12/22,54.5%)。在我们的病例系列中检测到19种不同的CRB1变体，包括12个错觉，3移相台，3废话，和1个拼接。其中,已经报告了12种变体，7、小说SS-OCT显示中央黄斑变薄（LCA组，P<0.0001),总视网膜较厚（P<0.0001），较薄的外视网膜（P<0.05），与健康对照相比，内部视网膜较厚（P<0.0001）。CRB1-eoRD的内/外（I/O）视网膜厚度比为3.0，高于健康对照组的1.2和其他遗传性视网膜疾病（IRD）的2.2（分别为P<0.0001和P=0.0027）。SS-OCTA显示CRB1-eoRD中浅表血管复合体和深层血管复合体的血管密度和灌注面积增加。
■LCA是CRB1-eoRD中经常出现的表型。说明了SS-OCT和SS-OCTA的独特功能，和新的生物标志物，I/O比,有助于早期诊断。从这项研究中获得的见解在确定潜在的即将进行的CRB1基因治疗的治疗窗口方面具有重要价值。
