The ability to measure retinal blood flow (RBF) accurately and reproducibly is crucial for diagnosing and monitoring ocular diseases such as glaucoma and hypertensive retinopathy. Impaired autoregulation of blood flow plays a key role in both the development and progression of glaucoma. Multimodal adaptive optics (mAO) using scanning laser ophthalmoscopy and optical coherence tomography offer superior spatial and temporal resolution and the ability to measure blood flow in retinal microvasculature. Here we evaluate RBF measurement reproducibility and repeatability using a mAO technique.
Although elevated intraocular pressure (IOP) is considered to be a major precursor for glaucoma, up to 45% of the patients with early glaucoma show signs of disease progression despite IOP reduction therapy. Studies have shown strong clinical evidence for abnormal ocular vessel function and impaired autoregulation of blood flow in early glaucoma subjects and its role in disease development and progression. Here we present direct measure of vascular dysfunction and autoregulation in three healthy human subjects using the erythrocyte mediate angiography and adaptive optics scanning laser ophthalmoscopy line-scan techniques. These novel quantitative blood flow metrics can potentially serve as a sensitive biomarker for early diagnosis and monitoring of ocular disease.
The photoreceptor (PR) – retinal pigment epithelium (RPE) – choriocapillaris (CC) complex is an extremely important group of layers in the outer retina. We demonstrate resolution of the CC vascular network across the macula, as well as the methodology to extract and quantify structural metrics from all three layers from averaged AO-OCT volumes. In diseased eyes, small changes in CC structure may portend the initiation of disease and therefore the investigation of CC structural changes may aid early disease diagnosis for many diseases, both prevalent and rare, that begin in the outer retina.
Recent clinical studies have shown that abnormal retinal blood is associated with many ocular diseases such as age-related macular degeneration, glaucoma, and diabetic retinopathy. Several ocular imaging techniques have been developed to measure retinal blood flow both invasively and non-invasively, including optical coherence tomography angiography (OCTA), erythrocyte mediated angiography (EMA), laser speckle imaging (LSI) and adaptive optics - scanning laser ophthalmoscopy (AO-SLO). Here we present a simple, compact, well-controlled clinical flow phantom model which allows flow evaluation across several techniques to aid in the clinical diagnosis of ocular diseases with abnormal blood flow.
Multiple sclerosis (MS) is a debilitating autoimmune disease characterized by lesions found in different regions of the central nervous system caused by overactive immune cells. MS also manifests in the retina, in which optic nerve pathology (such as optic neuritis) and neurodegenerative processes can affect inner retinal cells and structures. We observed the inner retina to be profoundly affected by MS, including nerve fiber bundle thinning, enlarged and lower density retinal ganglion cells, and the presence of microcysts. Longitudinal quantification of inner retinal changes enabled by AO-OCT may help accelerate the development of novel therapies for MS patients.
Glaucoma is an optic neuropathy characterized by loss of retinal ganglion cells and their axons. Glaucoma has a strong vascular component and decreased macular vessel density is known to be associated with glaucomatous damage. Adaptive optics – optical coherence tomography allows for the simultaneous quantification of vascular and ganglion cell densities. We observed a moderately strong correlation between ganglion cell and vessel densities across the macula, as well as some correlation at individual locations. Vascular density may prove to be a useful surrogate biomarker of glaucoma progression and with further study reveal new information on impairment of neurovascular coupling in glaucoma.
Transient stoppage of erythrocytes through different vascular beds has important implications for local tissue metabolism. By combining adaptive optics retinal imaging with erythrocyte-mediated angiography (AO-EMA), erythrocyte stasis events can be readily observed in the microvasculature of living human eyes. Localization of erythrocyte stasis using EMA alongside AO-based indocyanine green (ICG) angiography illustrate the notion that there is a previously uncharacterized population of erythrocytes in stasis residing in the smallest choroidal vessels. These observations are an important step towards elucidating the hemodynamic properties of the choroidal microcirculation and demonstrate a novel application of ICG imaging.
Microglia are central nervous system macrophages and the first responders to neural injury. Herein we characterize their distribution and motility in human eyes using a multimodal AO system. In healthy eyes, microglia are absent in the central macula up to ~5º eccentricity but their density increases monotonically at higher eccentricities. Microglia density decreases linearly with age. ILM microglia are relatively immobile for durations up to two weeks but their processes re-orient over timescales as short as minutes. The density, motility, and reactive state of microglia may serve as an ocular disease biomarker for early detection and progression monitoring.
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