Real-time OCT feedback-controlled RPE photodisruption in ex vivo porcine eyes using 8 microsecond laser pulses

Selective retinal pigment epithelium (RPE) photodisruption requires reliable real-time feedback dosimetry (RFD) to prevent unwanted overexposure. In this study, optical coherence tomography (OCT) based RFD was investigated in ex vivo porcine eyes exposed to laser pulses of 8 µs duration (wavelength: 532 nm, exposure area: 90 × 90 µm2, radiant exposure: 247 to 1975 mJ/µm2). For RFD, fringe washouts in time-resolved OCT M-scans (central wavelength: 870 nm, scan rate: 85 kHz) were compared to an RPE cell viability assay. Statistical analysis revealed a moderate correlation between RPE lesion size and applied treatment energy, suggesting RFD adaptation to inter- and intraindividual RPE pigmentation and ocular transmission

Dynamic OCT Signal Loss for Determining RPE Radiant Exposure Damage Thresholds in Microsecond Laser Microsurgery

Optical microsurgery of the retinal pigment epithelium (RPE) requires reliable real-time dosimetry to prevent unwanted overexposure of the neuroretina. The system used in this experiment implements optical coherence tomography (OCT) to detect the intentional elimination of RPE cells. We evaluated the performance of OCT dosimetry in terms of its ability to detect RPE cell damage caused by microsecond laser pulses of varying duration. Therefore, ex-vivo porcine RPE choroid sclera explants were embedded in an artificial eye and exposed to single laser pulses of 2–20 µs duration (wavelength: 532 nm, exposure area: 120 × 120 µm2, intensity modulation factor: 1.3). Simultaneously, time-resolved OCT M-scans were recorded (central wavelength: 870 nm, scan rate: 33 kHz). Post-irradiation, RPE cell damage was quantified using a calcein-AM viability assay and compared with an OCT-dosimetry algorithm. The results of our experiments show that the OCT-based analysis successfully predicts RPE cell damage. At its optimal operating point, the algorithm achieved a sensitivity of 89% and specificity of 94% for pulses of 6 µs duration and demonstrated the ability to precisely control radiant exposure of a wide range of pulse durations towards selective real-time laser microsurgery

Optical coherence tomography (OCT) - guided ophthalmic therapy

In this work, we demonstrate OCT-based guidance of two ophthalmic therapies, subretinal injection and selective retina therapy (SRT). Firstly, the “SMART,” a hand-held robotic surgical device actively guided by a common-path OCT (CP-OCT) distal sensor, improves in two aspects for being applied to subretinal injection: (i) A high-performance fiber probe based on high index epoxy lensed-fiber to enhance the CP-OCT retinal image quality; (ii) Automated retinal layer identification and tracking : retinal layer boundaries are tracked using convolutional neural network (CNN)-based segmentation for accurate subretinal injection guidance. It is shown that high index epoxy lensed-fiber probe improves the SNR and retinal image quality of the CP-OCT system. We propose and implement real-time retinal boundary tracking of A-scan OCT images using CNNs for accurate localization of a surgical tool tip. Unwanted axial motions of the surgical tools are compensated by a piezo-electric linear motor based on the retinal boundary tracking. A CNN-based CP-OCT distal sensor successfully tracks retinal boundaries, especially the PR/CH boundary for subretinal injection, and automatically guides the needle’s axial position in real-time. The micro-scale depth targeting accuracy of our system shows its promising possibility for clinical application. We also propose and demonstrate SRT monitoring based on speckle variance OCT (svOCT) for dosimetry control. M-scans of a phantom, ex vivo bovine iris, and ex vivo bovine retina are obtained by a swept-source OCT system during laser pulses irradiation. SvOCT images are calculated as interframe intensity variance of the sequence, and they show abrupt speckle variance change induced by laser pulse irradiation. The axially averaged svOCT signals show a sharp peak corresponding to each laser pulse, and the peak values are proportional to irradiated laser pulse energy. For the ex vivo retinal study, microscopic images of treated spots are obtained before and after removing the upper neural retinal layer to assess the damage in both RPE and neural layers. Spatial and temporal temperature distributions in the retina are numerically calculated in a 2D retinal model using COMSOL Multiphysics. We find that the svOCT peak values have a reliable correlation with the degree of retinal lesion formation. The temperature at the neural retina and RPE is estimated from the svOCT peak values using numerically calculated temperature, which is consistent with the observed lesion creation

Adaptive optics: principles and applications in ophthalmology

This is a comprehensive review of the principles and applications of adaptive optics (AO) in ophthalmology. It has been combined with flood illumination ophthalmoscopy, scanning laser ophthalmoscopy, as well as optical coherence tomography to image photoreceptors, retinal pigment epithelium (RPE), retinal ganglion cells, lamina cribrosa and the retinal vasculature. In this review, we highlight the clinical studies that have utilised AO to understand disease mechanisms. However, there are some limitations to using AO in a clinical setting including the cost of running an AO imaging service, the time needed to scan patients, the lack of normative databases and the very small size of area imaged. However, it is undoubtedly an exceptional research tool that enables visualisation of the retina at a cellular level

Clinical Applications of Artificial Intelligence in Glaucoma

Ophthalmology is one of the major imaging-intensive fields of medicine and thus has potential for extensive applications of artificial intelligence (AI) to advance diagnosis, drug efficacy, and other treatment-related aspects of ocular disease. AI has made impressive progress in ophthalmology within the past few years and two autonomous AIenabled systems have received US regulatory approvals for autonomously screening for mid-level or advanced diabetic retinopathy and macular edema. While no autonomous AI-enabled system for glaucoma screening has yet received US regulatory approval, numerous assistive AI-enabled software tools are already employed in commercialized instruments for quantifying retinal images and visual fields to augment glaucoma research and clinical practice. In this literature review (non-systematic), we provide an overview of AI applications in glaucoma, and highlight some limitations and considerations for AI integration and adoption into clinical practice

Aerospace medicine and biology: A continuing bibliography with indexes, supplement 162, January 1977

This bibliography lists 189 reports, articles, and other documents introduced into the NASA scientific and technical information system in December 1976

Quantitative Optical Studies of Oxidative Stress in Rodent Models of Eye and Lung Injuries

Optical imaging techniques have emerged as essential tools for reliable assessment of organ structure, biochemistry, and metabolic function. The recognition of metabolic markers for disease diagnosis has rekindled significant interest in the development of optical methods to measure the metabolism of the organ. The objective of my research was to employ optical imaging tools and to implement signal and image processing techniques capable of quantifying cellular metabolism for the diagnosis of diseases in human organs such as eyes and lungs. To accomplish this goal, three different tools, cryoimager, fluorescent microscope, and optical coherence tomography system were utilized to study the physiological metabolic markers and early structural changes due to injury in vitro, ex vivo, and at cryogenic temperatures. Cryogenic studies of eye injuries in animal models were performed using a fluorescence cryoimager to monitor two endogenous mitochondrial fluorophores, NADH (nicotinamide adenine dinucleotide) and FAD (flavin adenine dinucleotide). The mitochondrial redox ratio (NADH/ FAD), which is correlated with oxidative stress level, is an optical biomarker. The spatial distribution of mitochondrial redox ratio in injured eyes with different durations of the disease was delineated. This spatiotemporal information was helpful to investigate the heterogeneity of the ocular oxidative stress in the eyes during diseases and its association with retinopathy. To study the metabolism of the eye tissue, the retinal layer was targeted, which required high resolution imaging of the eye as well as developing a segmentation algorithm to quantitatively monitor and measure the metabolic redox state of the retina. To achieve a high signal to noise ratio in fluorescence image acquisition, the imaging was performed at cryogenic temperatures, which increased the quantum yield of the intrinsic fluorophores. Microscopy studies of cells were accomplished by using an inverted fluorescence microscope. Fixed slides of the retina tissue as well as exogenous fluorophores in live lung cells were imaged using fluorescent and time-lapse microscopy. Image processing techniques were developed to quantify subtle changes in the morphological parameters of the retinal vasculature network for the early detection of the injury. This implemented image cytometry tool was capable of segmenting vascular cells, and calculating vasculature features including: area, caliber, branch points, fractal dimension, and acellular capillaries, and classifying the healthy and injured retinas. Using time-lapse microscopy, the dynamics of cellular ROS (Reactive Oxygen Species) concentration was quantified and modeled in ROS-mediated lung injuries. A new methodology and an experimental protocol were designed to quantify changes of oxidative stress in different stress conditions and to localize the site of ROS in an uncoupled state of pulmonary artery endothelial cells (PAECs). Ex vivo studies of lung were conducted using a spectral-domain optical coherence tomography (SD-OCT) system and 3D scanned images of the lung were acquired. An image segmentation algorithm was developed to study the dynamics of structural changes in the lung alveoli in real time. Quantifying the structural dynamics provided information to diagnose pulmonary diseases and to evaluate the severity of the lung injury. The implemented software was able to quantify and present the changes in alveoli compliance in lung injury models, including edema. In conclusion, optical instrumentation, combined with signal and image processing techniques, provides quantitative physiological and structural information reflecting disease progression due to oxidative stress. This tool provides a unique capability to identify early points of intervention, which play a vital role in the early detection of eye and lung injuries. The future goal of this research is to translate optical imaging to clinical settings, and to transfer the instruments developed for animal models to the bedside for patient diagnosis

Optical coherence tomography and optical coherence tomography angiography in uveitis : a review

Optical coherence tomography (OCT) has dramatically changed the understanding and management of uveitis and other ocular conditions. Currently, OCT angiography (OCTA) combines structural information with the visualization of blood flow within the imaged area. The aim of this review is to present the basic principles of OCT and OCTA interpretation and to investigate the role of these imaging techniques in the diagnosis and management of uveitis. Common complications of intraocular inflammation such as macular oedema and inflammatory choroidal neovascularization are often diagnosed and followed with OCT/OCTA scans. However, uveitis specialists can obtain much more information from tomographic scans. This review provides a comprehensive description of typical OCT/OCTA findings characterizing different ocular structures in uveitis, proceeding from the cornea to the choroid. A careful interpretation of OCT/OCTA images can help in the differential diagnosis, the prediction of clinical outcomes, and the follow-up of patients with uveitis