Point-of-care ophthalmic diagnostic imaging of retinopathy of prematurity

早产儿视网膜病变（ROP）是一种影响早产儿的增殖性视网膜血管疾病， 儿童失明的主要原因。ROP在交界处的间接检眼镜下诊断和分期 在血管化和无血管视网膜之间（即，视网膜脱离（RD）是视网膜脱离的一种表现形式。 以及血管扩张和迂曲增加。虽然存在手术和药物治疗， 结构和视力结果（<20/200视力或失明）发生在>50%的严重病例中，因为RD，裂， 并且血管异常在临床检查中经常被遗漏。常规检眼镜检查 使用眼底镜检查进行。然而，视网膜微血管系统即使在 结合外源性荧光素造影剂。光学相干层析成像（OCT）是目前的黄金- 成人眼科诊断成像标准和OCT血管造影术（OCT-A）的发展已经 使得能够在不需要外源性对比的情况下对视网膜脉管系统进行体内成像。虽然一些研究 研究小组开发了手持式OCT/OCTA成像系统并在ROP患者中演示了成像， 跟踪ROP进展的视网膜脉管系统的纵向定量成像仍然受到几个关键因素的限制， 挑战：1）婴儿无法固定，无法重复成像感兴趣区域（ROI）; 2） 手持成像加上婴儿运动导致明显伪影和较差的OCTA对比度; 3） OCT/OCTA质量因玻璃体/前房混浊而严重降低，这在ROP中很常见; 4） 周边视网膜血管变化对于ROP分期很重要，但OCT/OCTA针对这些ROI， 困难; 5）血管容积提供临床相关特征，如扩张和迂曲，但OCTA 传统上仅使用正面投影来评估。为了克服这些限制，我们开发了一个 结合硬件和图像处理技术，用于手持式OCT/OCTA 光谱编码相干断层扫描和反射（SECTR）眼科成像平台。SECTR 同时获取正交正面反射率和横截面OCT图像， 用于运动校正和多体积镶嵌的体积配准。我们假设 将这些技术转化为护理点眼科成像系统将允许鲁棒的， 视网膜血管变化的可重复的和定量的纵向跟踪，这将提高诊断 和早产儿ROP分期准确性。我们的目标是开发定制硬件（AIM 1）和图像分析 管道（AIM 2）优化的手持SECTR成像在婴儿的眼睛。这些技术将在 ROP的结构和功能变化的纵向成像（AIM 3），并提供定量的洞察力， SECTR成像的可行性有利于治疗决策。所提出的装置和定量分析管线 不限于ROP病例，并且可以广泛地应用于任何眼科领域， 护理OCT/OCTA可以改善当前的临床护理标准。

Retinopathy of prematurity (ROP) is a proliferative retinal vascular disease that affects preterm infants and a major cause of childhood blindness. ROP is diagnosed and staged under indirect ophthalmoscopy at the junction between the vascularized and avascular retina (i.e., periphery) using features such as retinal detachment (RD) and increased vascular dilatation and tortuosity. While surgical and pharmacologic therapies exist, poor structural and visual outcomes (<20/200 vision or blindness) occur in >50% of severe cases because RD, schisis, and vascular abnormalities are often missed on clinical examination. Conventional ophthalmoscopic examination in infants is performed using fundoscopy. However, retinal microvasculature is poorly visualized even when combined with exogenous fluorescein contrast. Optical coherence tomography (OCT) is currently the gold- standard for ophthalmic diagnostic imaging in adults and developments in OCT angiography (OCT-A) have enabled in vivo imaging of retinal vasculature without the need for exogenous contrast. While several research groups have developed handheld OCT/OCTA imaging systems and demonstrated imaging in ROP patients, longitudinal quantitative imaging of retinal vasculature to track ROP progression remains limited by several key challenges: 1) infants cannot fixate, making repeated imaging of regions-of-interest (ROIs) impossible; 2) handheld imaging coupled with infant motion results in significant artifacts and poor OCTA contrast; 3) OCT/OCTA quality is severely degraded by vitreous/anterior chamber haze, which is common in ROP; 4) peripheral retinal vascular changes are important for ROP staging but aiming of OCT/OCTA at these ROIs is difficult; 5) vascular volumes provide clinically relevant features such as dilatation and tortuosity, but OCTA is conventionally assessed using only en face projections. To overcome these limitations, we have developed a combination of hardware and image-processing technologies for handheld OCT/OCTA built around a multimodal spectrally encoded coherence tomography and reflectometry (SECTR) ophthalmic imaging platform. SECTR simultaneously acquires orthogonal en face reflectance and cross-sectional OCT images that uniquely benefits volumetric registration for motion-correction and multi-volumetric mosaicking. We hypothesize that the translation of these technologies into a point-of-care ophthalmic imaging system will allow for robust, reproducible, and quantitative longitudinal tracking of retinal vascular changes, which will improve the diagnostic and staging accuracy of ROP in preterm infants. We aim to develop custom hardware (AIM 1) and image analysis pipelines (AIM 2) optimized for handheld SECTR imaging in infant eyes. These technologies will be validated in longitudinal imaging of structural and functional changes in ROP (AIM 3) and provide quantitative insight on the viability of SECTR imaging to benefit treatment decisions. The proposed device and quantitative analysis pipeline are not limited to ROP cases and can be broadly applied in any area of ophthalmology where a robust point-of- care OCT/OCTA may improve current clinical standard-of-care.