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

描述(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眼底镜(AOSLO)和光谱域光学相干断层扫描(SDOCT)来识别人类糖尿病眼的血管和神经视网膜的组合特征，这些特征可以预测未来的视力损失和抗血管内皮生长因子(AntiVEGF)药物的反应。尽管在治疗糖尿病眼并发症方面取得了进展，包括激光光凝以及最近玻璃体内类固醇和抗血管内皮生长因子药物的使用，但糖尿病仍然是劳动年龄成年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黄斑水肿(DME)和增殖性糖尿病视网膜病变(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，这些 努力解决了一项紧迫的需求。准确预测术后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，并加快新疗法的疗效评估。本文提出的研究利用AOSLO的创新技术来矫正单眼90%以上的光学像差，导致视网膜图像分辨率达到2�m。使用AOSLO，我们的团队已经可视化并展示了具有特征性的DR病变的血流灌注，例如微动脉瘤和视网膜新生血管，即使它们在标准的眼底照片上无法识别或明显地灌流。我们的初步数据表明，AOSLO上微动脉瘤的壁高反射率和SDOCT图像上视网膜内层的紊乱都与DME患者的视力下降有关。此外，我们已经证明，即使DME已经解决，视网膜内层的破坏也可以预测未来的VA。我们现在建议进行长期的前瞻性研究，以这些早期发现为基础，开发多变量模型来预测患有DME和增殖性DR的眼睛未来的视力和对抗VEGF治疗的反应。在人眼中以高分辨率同时评估体内视网膜血管和神经成分将允许对糖尿病视网膜病理进行全面评估，并增加识别预测视觉结果和抗VEGF治疗反应的解剖因素的机会。这一建议充分利用了AOSLO中采用的可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，并使其能够接触到独特的Joslin糖尿病中心患者群体。这一队列中糖尿病眼部病变的高发生率将使拟议的研究在整个5年的时间框架内很容易实现。鉴于这些结果可能有助于预测糖尿病眼的视力结果和对抗血管内皮生长因子治疗的反应，这项工作可能会对未来的患者护理战略和DR和DME的新疗法研究产生重大影响。

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.