Predicting diabetic macular edema using functional measures

描述(申请人提供)：我们研究的长期目标是通过确定糖尿病早期发生的功能性措施并预测糖尿病眼并发症来预防糖尿病眼病造成的视力丧失。糖尿病眼部并发症是美国20-74岁工作年龄成年人失明的主要原因。在2型糖尿病患者中，90%的糖尿病病例是导致视力丧失的主要原因是糖尿病黄斑、视网膜积液。目前对浮肿的治疗旨在减缓进展，并在发生相当大的视网膜损伤和视力丧失后应用。这些疗法，主要是激光疗法，侧重于减缓视力丧失或挽救中心视力(敏感度)。较新的抗血管内皮生长因子治疗确实可以提高视力，但同样，这种治疗是在视力丧失和结构性损伤后应用的。旨在预防或早期治疗的临床试验将在很大程度上依赖于开发出识别患者和视网膜位置存在视网膜浮肿风险的方法。我们已经证明，多焦视网膜电信号(MfERG)可以同时快速、客观地评估103个不同视网膜位置的视网膜神经功能。MfERG计时的测量已经用于我们的模型中，预测有或没有既往视网膜病变的眼睛出现新的视网膜病变体征。最近，我们将注意力转向开发糖尿病黄斑水肿发病的预测模型。预测黄斑水肿的初步模型具有相当好的灵敏度和特异度，它使用mfERG作为眼睛唯一的功能指标，mfERG主要是接受后视锥系统的反应。然而，我们现在将开发一个模型，该模型还包括视杆细胞和视锥细胞光感受器(PR)和视网膜色素上皮(RPE)功能的测量，这两种功能都已知受到糖尿病的影响。此外，RPE还负责将液体泵出视网膜。因此，RPE中的功能缺陷导致黄斑水肿。它的功能是用眼电(EOG)无创测量的。RPE对于视杆和视锥的完整性和功能也是必不可少的。全场闪光视网膜电信号(ERG)提供视杆和视锥功能的测量。因此，新的模式将包括这些措施的RPE和公关功能。这些问题涉及黄斑水肿(RPE)或受黄斑水肿(PR)影响。MfERG是唯一可以识别特定视网膜位置功能异常的客观方法，也将包括在内。能够预测糖尿病黄斑水肿将在哪里发展(特定的视网膜位置)，以及患者的眼睛将为临床医生提供强大的管理工具，用于尚未开发的新治疗方法。更直接的是，从研究的角度来看，通过减少所需的受试者数量和缩短建立有意义的结果所需的研究时间，识别“高危”人群的能力将大大简化临床试验。这将可能节省成本，并有能力更快地将新的候选治疗或干预措施引入临床。

DESCRIPTION (provided by applicant): The long-term goal of our research is to prevent sight loss due to diabetic eye disease by identifying functional measures that occur early in diabetes and predict diabetes eye complications. Diabetic eye complications are the leading cause of blindness among working age adults aged 20-74 in the US. Among people with Type 2 diabetes, 90% of cases of diabetes, the leading cause of sight loss are diabetic macular, accumulation of fluid in the retina. Current treatments of edema are aimed at slowing progression and are applied after considerable retinal damage and loss of vision have occurred. These treatments, mainly laser treatments, focus on slowing acuity loss or saving central vision (acuity). Newer anti-VEGF treatments do improve acuity, but again, this treatment is applied after sight loss and structural damage. Clinical trials aimed at prevention or early treatment will rely heavily on developing means of identifying patients and retinal locations at risk for retinal edema. We have shown that the multifocal electroretinogram (mfERG) quickly and objectively evaluates retinal neural function at 103 separate retinal locations simultaneously. The measure of mfERG timing has been used in our models that predict new retinopathic signs in eyes with or without previous retinopathy. Most recently, we have turned our attention to developing a predictive model of diabetic macular edema onset. A preliminary model predictive of macular edema, which has fairly good sensitivity and specificity, uses the mfERG, which is predominantly a post-receptoral cone system response, as the sole functional measure of the eye. However, we will now develop a model that also includes measures of rod and cone photoreceptor (PR) function and retinal pigment epithelial (RPE) function, both of which are known to be affected by diabetes. Further, the RPE is responsible for pumping fluid out of the retina. Therefore functional deficits in the RPE contribute to macular edema. Its function is measured non-invasively using the electro-oculogram (EOG). The RPE is also essential for the integrity and function of the rods and cones. The full field flash electroretinogram (ERG) provides a measure of rod and cone function. Thus, the new model will include these measures of RPE and PR function. These are issues that are implicated in (RPE) or affected by (PR) macular edema. mfERGs, which is the only objective method that can identify functional abnormalities at specific retinal locations, will also be included. The ability to predict where diabetic macular edema will develop (specific retinal locations) and in which patients' eyes will provide clinicians with powerful management tools for new treatments yet to be developed. More immediately, from a research perspective, the ability to identify 'at risk' populations will greatly streamline clinical trials by reducing the number of subjects required and reducing the study period needed to establish meaningful results. This will make possible cost savings and the ability to more quickly bring new candidate treatments or interventions to the clinic.