Progressive optic disc cupping over 20 years in a patient with TBK1-associated glaucoma.
Progressive optic disc cupping over 20 years in a patient with TBK1-associated glaucoma.
复制标题
TBK1 相关青光眼患者 20 年来进行性视盘拔罐。
DOI：
10.1016/j.ogla.2019.11.003
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发表时间：
2020
影响因子：
--
通讯作者：
Fingert,JohnH
中科院分区：
文献类型：
--
作者：
Sears,NathanC;Darbro,BenjaminW;Alward,WallaceLM;Fingert,JohnH
原发性开角型青光眼是视力障碍的主要原因，其特征是视盘凹陷和视野丧失的典型模式。虽然高眼压 (IOP) 是发生疾病的危险因素，但青光眼在任何压力下都可能发生。最大 IOP 低于 21 mm Hg 时发生的青光眼被称为正常眼压性青光眼 (NTG)。青光眼具有高度遗传性，许多与 NTG 发病机制有关的基因已被发现。 optineurin (OPTN)、1 TANK 结合激酶 1 (TBK1)、2 或 myocilin (MYOC) 3 的突变均能够引起青光眼，而其他遗传或环境因素的影响很小。这些基因的突变约占 NTG 的 3%。 1-3TBK1 相关 NTG 是由正常 TBK1 基因序列的重复或三倍引起的。这些 TBK1 基因剂量突变已在非裔美国人、2 名白种人、2、4、5 名和亚洲人 6、7 名 NTG 患者中检测到，但尚未在大型公共数据库 (gnomAD.broadinstitute.org) 的 10,000 多个个体的基因组中发现。 TBK1 基因重复和三倍突变与早发性青光眼相关，这种青光眼经常表现为较大的杯盘比和最大 IOP< 21 mm Hg。 2 先前对 TBK1 相关 NTG 的研究报道，诊断时的平均年龄为 29 至 36 岁；第一次检查时平均杯盘比为 0.85 至 0.93；平均最大眼压为 18 至 19 毫米汞柱。 2 一些携带 TBK1 突变的 NTG 患者中央角膜较薄，但在该患者群体中观察到角膜厚度存在较大差异。 2, 5 在 TBK1 相关青光眼患者中检测到典型的青光眼视野，包括弓形缺损、鼻台阶、中央缺损和广泛性缩窄。 2 尽管 TBK1 相关青光眼临床表型的许多关键特征已被证实
Primary open angle glaucoma is a leading cause of visual impairment that is characterized by cupping of the optic disc and stereotypical patterns of visual field loss. While high intraocular pressure (IOP) is a risk factor for developing disease, glaucoma can occur at any pressure. Glaucoma that occurs with maximum lOPs of less than 21 mm Hg has been termed normal tension glaucoma (NTG). Glaucoma is highly heritable and many genes that contribute to the pathogenesis of NTG have been discovered. Mutations in either optineurin (OPTN), 1 TANK-binding kinase 1 (TBK1), 2 or myocilin (MYOC) 3 are each capable of causing glaucoma with little influence from other genetic or environmental factors. Mutations in these genes are responsible for approximately 3% of NTG. 1–3TBK1-associated NTG is caused by duplication or triplication of the normal TBK1 gene sequence. These TBK1 gene-dosage mutations have been detected in African American, 2 Caucasian, 2, 4, 5 and Asian6, 7 NTG patients and have not been identified in the genomes of over 10,000 individuals in a large public database (gnomAD. broadinstitute. org). TBK1 gene duplication and triplication mutations are associated with early-onset glaucoma that frequently presents with large cup-to-disc ratios and maximum lOPs of< 21 mm Hg. 2 Prior studies of TBK1-associated NTG have reported a mean age at diagnosis of 29 to 36 years; mean cup-to-disc ratio of 0.85 to 0.93 at first examination; and mean maximum IOP of 18 to 19 mm Hg. 2 Some NTG patients with TBK1 mutations have thin central corneas, however, a broad range of corneal thickness has been observed in this patient population. 2, 5 Typical glaucomatous visual fields have been detected in patients with TBK1-associated glaucoma, including arcuate defects, nasal steps, central defects, and generalized constriction. 2 Although many key features of the clinical phenotype of TBK1-associated glaucoma have