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

早产儿视网膜病变(ROP)是一种增生性视网膜血管疾病，影响早产儿和 儿童失明的主要原因。在交界处的间接眼底镜下诊断和分期ROP 利用视网膜脱离(RD)等特征，在有血管的视网膜和无血管的视网膜(即，外围)之间 血管扩张和弯曲度增加。虽然有手术和药物治疗，但很差 结构和视觉结果(20/200视力或失明)发生在50%的严重病例中，因为RD，裂伤， 而血管异常在临床检查中往往被遗漏。常规检眼镜检查 在婴儿中使用眼底镜进行检查。然而，视网膜微血管的可视化很差，即使当 结合外源性荧光素对比剂。光学相干层析成像(OCT)是目前的黄金技术-- 成人眼科诊断成像标准和OCT血管造影术(OCT-A)的进展 实现了视网膜血管系统的活体成像，而不需要外部对比。虽然有几项研究 研究小组开发了手持OCT/OCTA成像系统，并在ROP患者中演示了成像， 追踪ROP进展的视网膜血管的纵向定量成像仍然受到几个关键因素的限制 挑战：1)婴儿不能注视，使感兴趣区域(ROI)无法重复成像；2) 手持成像结合婴儿运动导致明显的伪影和较差的OCTA对比度；3) OCT/OCTA质量因玻璃体/前房混浊而严重退化，这在ROP中很常见；4) 周边视网膜血管改变对ROP分期很重要，但OCT/OCTA针对这些ROI 困难；5)血管体积提供临床相关特征，如扩张和弯曲，但OCTA 传统上仅使用面部投影进行评估。为了克服这些限制，我们开发了一种 硬件和图像处理技术相结合的手持OCT/OCTA围绕多模式构建 光谱编码相干层析成像和反射仪(SECTR)眼科成像平台。SECTR 同时获得正交的面部反射率和横截面OCT图像，这对 用于运动校正和多体积拼接的体积配准。我们假设 将这些技术转化为护理点眼成像系统将允许强大的、 可重复性的，定量的视网膜血管变化的纵向跟踪，这将提高诊断 早产儿ROP分期的准确性。我们的目标是开发定制硬件(AIM 1)和图像分析 针对婴儿眼部手持SECTR成像进行优化的管道(AIM 2)。这些技术将在 ROP结构和功能变化的纵向成像(AIM 3)，并提供对ROP的定量洞察 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流水线 不仅限于ROP病例，还可以广泛应用于任何眼科领域，在这些领域中， CARE OCT/OCTA可能会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.