Predicting Outcomes & Anti-VEGF Response in Diabetic Eyes by Adaptive Optics SLO

描述（由申请人提供）： 拟议的研究将利用体内、超高分辨率、自适应光学扫描激光检眼镜（AOSLO）与谱域光学相干断层扫描（SDOCT）相结合，以确定人类糖尿病眼血管和神经视网膜的组合特征，这些特征可预测未来视力丧失和对抗血管内皮生长因子（antiVEGF）药物的反应。尽管糖尿病眼部并发症的治疗取得了进展，包括激光光凝和最近使用的玻璃体内类固醇和抗VEGF药物，但糖尿病仍然是工作年龄成人可预防失明的主要原因。鉴于糖尿病及其相关并发症糖尿病性黄斑水肿（DME）和增殖性糖尿病性视网膜病变（DR）的全球流行迅速增加，以及我们目前无法可靠地预测未来的视力结果， 努力解决一个关键的需要。准确预测长期视觉潜力的能力， DME的治疗可以显著改善对患者的护理，揭示视力丧失的潜在机制，并加速新疗法的疗效评估。这里提出的研究利用AOSLO的创新技术来校正单个眼睛中超过90%的光学像差，从而使视网膜图像分辨率达到2 μ m。使用AOSLO，我们的研究小组已经可视化并展示了特征性DR病变的灌注，例如微动脉瘤和视网膜新生血管，即使它们在标准眼底照片上无法识别或可见灌注。我们的初步数据表明，AOSLO上的微动脉瘤壁高反射率和SDOCT图像上的视网膜内层破坏都与DME患者眼睛的视力下降相关。此外，我们已经表明，即使DME已经解决，视网膜内层紊乱也是未来VA的预测。我们现在提出了长期的前瞻性研究，将建立在这些早期发现的基础上，以开发多变量模型，预测DME和增殖性DR眼中未来的视力和对抗VEGF的治疗反应。在人眼中以高分辨率同时评价视网膜血管和神经成分将允许全面评价糖尿病视网膜病理学，并增加识别预测视力结果和对抗VEGF治疗反应的解剖学因素的机会。该提案充分利用了AOSLO沿着的变形镜技术所代表的技术进步，以及研究团队在设计和实施糖尿病视网膜病变临床试验方面的丰富经验，以及其对独特的Joslin糖尿病中心患者人群的访问。该队列中糖尿病眼部病理学的高发生率将使拟定的研究在整个5年时间范围内容易实现。鉴于这些结果可能有助于预测糖尿病患者的视力结果和对抗VEGF治疗的反应，这项工作可能对未来的患者护理策略和DR和DME新型治疗方法的研究产生重大影响。

DESCRIPTION (provided by applicant): The proposed study will utilize in vivo, ultra-high resolution, adaptive optics scanning laser ophthalmoscopy (AOSLO) in combination with spectral domain optical coherence tomography (SDOCT) to identify combined characteristics of vascular and neural retina in the human diabetic eye that predict future vision loss and response to anti-vascular endothelial growth factor (antiVEGF) agents. Despite advances in treatment for diabetic eye complications, including laser photocoagulation and the recent use of intravitreal steroids and antiVEGF agents, diabetes continues to be the leading cause of preventable blindness in working age adults. Given the rapidly increasing global epidemic of diabetes and its associated complications of diabetic macular edema (DME) and proliferative diabetic retinopathy (DR) as well as our current inability to reliably predict future visual outcomes, these efforts address a critical need. The ability to accurately predict long term visual potential after treatment for DME could dramatically improve care for patients, reveal underlying mechanisms of vision loss, and speed efficacy evaluation of novel therapies. The studies proposed here utilize the innovative technology of AOSLO to correct over 90% of the optical aberrations in an individual eye resulting in retinal image resolution of 2 �m. Using AOSLO, our group has visualized and demonstrated perfusion of characteristic DR lesions such as microaneurysms and retinal neovascularization even when they are not identifiable or visibly perfused on standard fundus photographs. Our preliminary data demonstrate that wall hyperreflectivity of microaneurysms on AOSLO and retinal inner layer disorganization on SDOCT images are both associated with worse visual acuity in eyes of patients with DME. Furthermore, we have shown that retinal inner layer disorganization is predictive of future VA even once DME has resolved. We now propose long term, prospective studies that will build upon these early findings to develop multivariable models predictive of future vision and treatment response to antiVEGF in eyes with DME and proliferative DR. The simultaneous evaluation of retinal vascular and neural components in vivo at high resolution in the human eye will allow comprehensive evaluation of diabetic retinal pathology, and increase chances for identification of anatomic factors predictive of visual outcome and response to antiVEGF therapy. This proposal leverages the technological advances represented by deformable mirror technology incorporated into the AOSLO along with the study team's extensive experience in the design and implementation of clinical trials for diabetic retinopathy and its access to the unique Joslin Diabetes Center patient population. The high rates of diabetic ocular pathology in this cohort will make the proposed studies readily achievable within the overall 5 year time frame. Given that these results may help predict vision outcomes and response to antiVEGF treatment in the diabetic eye, this work could have a major impact on future strategies for patient care and research for novel therapeutics in DR and DME.