The eye as a window into sickle cell disease morbidity

项目摘要/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)是对视力的威胁 并发症，据报道盲目率为10%。SCR损伤通常始于儿童时期，并随着 年龄。在SCR的早期，小的周边视网膜血管阻塞，也被称为“视网膜卒中”，通常是 没有任何症状。然而，随着疾病的发展，异常血管开始生长(新生血管 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 视力丧失。目前，还没有经过验证的预防SCR的方法，治疗方案主要集中在 抑制增生性SCR的进展。及时诊断SCR是早期治疗的重要一步， 它可以防止视力丧失。诊断策略侧重于对视网膜中风和异常的迹象进行可视化 血管生长。NIH指南建议每年通过扩张的眼底镜检查进行SCR筛查 眼睛从10岁开始，敏感度低。视网膜新生血管的病理过程是一个 正在积极调查中的复杂现象。在这项申请中提出的研究，眼睛作为一种 了解镰状细胞疾病发病率的窗口，将结合使用标准和新的非侵入性 SCD儿童视网膜循环和结构改变的诊断方法。使用这些 技术将提高我们准确诊断和监测儿童SCR的能力，并提供更好的 了解这种疾病的发病机制。此外，敏感和具体评估的价值 SCD的眼部改变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， 眼部表现有助于诊断和监测整个疾病的进展。因此，来自 拟议的眼科检查可能会阐明视网膜损伤和其他眼科疾病之间的联系。 危险器官，尤其是SCD的大脑。通过这项研究，我们将完善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，并启动早期干预。 将视网膜表现与临床数据相关联，可能有助于了解SCD的其他血管并发症，如 作为脑血管疾病。这项研究的长期目标是加强SCR的早期检测并开发 减缓SCR发展为增殖性视网膜病变和失明的治疗策略，降低 SCR的社会负担和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.