The eye as a window into sickle cell disease morbidity

项目概要/摘要 镰状细胞病（SCD）是美国人口中最常见的基因突变，影响 大约10万美国人。作为一种全身性疾病，SCD攻击包括眼睛在内的多个器官。 虽然SCD几乎可以影响眼睛的所有结构，但镰状细胞性视网膜病变（SCR）是视力威胁 并发症，据报道失明率为10%。SCR损伤通常始于儿童期， 年龄在SCR的早期，小的外周视网膜血管闭塞，也称为“视网膜中风”，通常是视网膜病变的主要原因。 无症状。然而，随着疾病的进展，异常血管开始生长（新血管形成 或增殖性变化）。晚期增殖性SCR可导致眼内出血、视网膜脱离和视网膜脱离。 视力丧失目前，还没有经过证实的方法来预防SCR，治疗方案的重点是 阻止增殖性SCR的进展。及时诊断SCR是早期治疗的重要步骤， 可以防止视力下降。诊断策略集中在可视化的迹象视网膜中风和异常 血管生长NIH指南建议每年通过扩瞳眼底镜检查对SCR进行筛查， 眼睛从十岁开始，敏感度很低。视网膜新生血管的病理过程是一个复杂的过程， 正在积极调查的复杂现象。在这项申请中提出的研究，眼睛作为一个 镰状细胞病发病率窗口，将利用标准和新型非侵入性 诊断模式，以检查视网膜循环和结构的变化，儿童与SCD。使用这些 技术将提高我们准确诊断和监测儿童SCR的能力， 了解疾病的机制。此外，敏感和具体评估的价值 SCD的眼部变化并不局限于挽救视力。对于许多神经系统疾病和全身性疾病， 眼部发现有助于诊断和监测总体疾病进展。因此， 建议的眼科检查可以阐明视网膜损伤与其他AT- 危险器官，尤其是SCD患者的大脑。通过这项研究，我们将提高我们预测进展的能力， 评估治疗效果，制定更有效的监测指南，并开始早期干预。 将视网膜检查结果与临床数据相关联可能有助于了解SCD的其他血管并发症， 脑血管疾病本研究的长期目标是加强SCR的早期检测， 治疗策略，以减缓SCR向增殖性视网膜病变和失明的进展， 减少SCR的社会负担并改善这些患者的生活质量。

PROJECT SUMMARY/ABSTRACT Sickle cell disease (SCD) is the most common genetic mutation among the US population, affecting approximately 100,000 Americans. As a systemic illness, SCD attacks multiple organs including the eyes. Although SCD can affect nearly all structures in the eye, sickle cell retinopathy (SCR) is the vision threatening complication with a reported 10% blindness rate. SCR damage often begins in childhood and progresses with age. Early in SCR, small peripheral retinal vascular occlusions, also known as “retinal stroke”, are typically asymptomatic. However, as the disease progresses, abnormal blood vessels begin to grow (neovascularization or proliferative change). Advanced proliferative SCR can lead to intraocular hemorrhage, retinal detachment and vision loss. Currently, there are no proven methods to prevent SCR, and treatment options are focused on deterring the progression of proliferative SCR. Prompt diagnosis of SCR is an important step for early treatment, which can prevent vision loss. The diagnostic strategies focus on visualizing signs of retinal stroke and abnormal vessel growth. NIH guidelines recommend annual screening for SCR by dilated funduscopic examination of the eye beginning at age ten, which has low sensitivity. The pathological process of retinal neovascularization is a complex phenomenon under active investigation. The research proposed in this application, The Eye as a Window into Sickle Cell Disease Morbidity, will utilize a combination of standard and novel noninvasive diagnostic modalities to examine retinal circulation and structure changes in children with SCD. Using these techniques will improve our ability to accurately diagnose and monitor SCR in children and provide a better understanding of the mechanism of the disease. Furthermore, the value of sensitive and specific assessments of ocular changes in SCD is not limited to saving vision. For many neurologic conditions and systemic illnesses, ocular findings aid in both diagnosis and monitoring of overall disease progression. Thus, findings from the proposed ophthalmologic examinations may elucidate a link between retinal damage and damage to other at- risk organs, especially the brain in SCD. Through this study, we will refine our ability to predict progression, assess therapeutic efficacy, develop more effective monitoring guidelines and initiate early interventions. Correlating retinal findings with clinical data may provide insight into other vascular complications of SCD, such as cerebrovascular disease. The long-term goal of this study is to enhance early detection of SCR and develop treatment strategies to slow the progression of SCR toward proliferative retinopathy and blindness, lowering the societal burden of SCR and improving the quality of life for these patients.