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Purpose To investigate the use of imaging modalities in the volumetric measurement of the subretinal space and examine the volume of subretinal blebs created by a subretinal drug delivery device utilizing microscope-integrated optical coherence tomography (MIOCT). Methods An MIOCT image-based volume measurement method was developed and assessed for accuracy and reproducibility by imaging ceramic spheres of known size that were surgically implanted into ex vivo porcine eyes. This method was then used to measure subretinal blebs created in 10 porcine eyes by injection of balanced salt solution utilizing a subretinal delivery device via a suprachoroidal cannula. Bleb volumes obtained from MIOCT were compared to the intended injection volume. Results Validation of image-based volume measurements of ceramic spheres showed accuracy to ±0.029 µL (5.6%) for objects imaged over the posterior pole and ±0.025 µL (4.8%) over peripheral retina. The mean expected injection volume from extraocular tests of the suprachoroidal cannula was 66.44 µL (σ = 2.4 µL). The mean injection volume as measured by the MIOCT imaging method was 54.8 µL (σ = 12.3 µL), or 82.48% of expected injection volume. Conclusions MIOCT can measure the volume of subretinal blebs with accuracy and precision. The novel suprachoroidal approach using a subretinal delivery device was able to deliver greater than 80% of expected injection volume into the subretinal space, as assessed by MIOCT. Translational relevance MIOCT provides a method for visualization, and analysis of images enables surgeons to quantify and evaluate the success of subretinal drug delivery via a suprachoroidal approach.

Microscope-integrated optical coherence tomography (MIOCT) systems allow for 4D visualization of thin, semi-transparent structures during ophthalmic microsurgery. While these visualizations have greatly increased the information available to surgeons, new surgical techniques, such as subretinal injections of gene therapies, would benefit from quantitative measurements of structures imaged using OCT. Calibration of true scan dimensions in OCT is complicated by inter-patient ocular variability as well as poor control of scanner-patient alignment. We introduce novel measurement techniques for calibration and de-warping of OCT imagery which allows for accurate measurement of intraocular structures including subretinal microinjection bleb volumes in the ocular posterior segment.

Ophthalmic surgery is typically performed through an en-face only surgical microscope that provides limited depth information. This work introduces a high speed (400 kHz) microscope integrated optical coherence tomography (MIOCT) system which provides real time volumetric “4D” visualization via a heads-up stereoscopic display. The MIOCT system provides sub retinal visualization of tools and enables surgeons to perform delicate manipulation of retinal structures during mock surgical procedures. Following these mock surgical procedures in porcine eyes, this system will be readily translated into human ophthalmic microsurgery.

Purpose Subretinal injections of therapeutics are commonly used to treat ocular diseases. Accurate dosing of therapeutics at target locations is crucial but difficult to achieve using subretinal injections due to leakage, and there is no method available to measure the volume of therapeutics successfully administered to the subretinal location during surgery. Here we introduce the first automatic method for quantifying the volume of subretinal blebs, using porcine eyes injected with Ringer’s lactate solution as samples. Design Experimental study. Methods Microscope-integrated optical coherence tomography was utilized to obtain 3D visualization of subretinal blebs in porcine eyes at Duke Eye Center. Two different injection phases were imaged and analyzed in 15 eyes (30 volumes), selected from a total of 37 eyes. The inclusion/exclusion criteria were set independently from the algorithm-development and testing team. A novel lightweight, deep learning-based algorithm was designed to segment subretinal blebs boundaries. A cross-validation method was used to avoid selection bias. An ensemble-classifier strategy was applied to generate final results for the test dataset. Results The algorithm performs significantly better than four other state-of-the-art deep learning-based segmentation methods, achieving an F1 score of 93.86 ± 1.17% and 96.90 ± 0.59% on the independent test data for entry and full blebs, respectively. Conclusion The proposed algorithm accurately segmented the volumetric boundaries of Ringer’s lactate solution delivered into the subretinal space of porcine eyes with robust performance and real-time speed. This is the first step for future applications in computer-guided delivery of therapeutics into the subretinal space in human subjects.

High speed optical coherence tomography (OCT) systems with A-scan rates greater than 100 kHz allow for 4D visualizations in applications such as intraoperative OCT. However, traditional triangle or sawtooth waveforms used to drive galvanometer scanners often have frequency content that exceeds the bandwidth of the scanners, leading to distorted scans. Sinusoidal waveforms used to drive resonant scanners also lead to distorted scans due to the nonlinear scan velocity. Additionally, with raster scan patterns, the scanner needs time to stop and reverse direction in between B-scans, leading to significant acquisition dead time. Continuous scan patterns such as constant frequency spiral scanning or Lissajous scanning no longer have acquisition dead times, but suffer from non-uniform sampling across the imaging plane. We previously introduced constant linear velocity (CLV) spiral scanning as a novel scan pattern to maximize the data acquisition efficiency of high speed OCT systems. While this continuous scan pattern has no acquisition dead time and produces more uniform sampling compared to raster scanning, it required significant processing time. We introduce a processing pipeline implemented using CUDA in C++, which drastically reduces the amount of processing time needed, allowing real time visualization of 4D OCT data. To demonstrate its potential utility, we used CLV scanning with a 100 kHz swept-source OCT system to image retinas of enucleated porcine eyes undergoing mock ophthalmic surgery movements. Additionally, we rendered these volumes in virtual reality (VR) in real time, allowing for interactive manipulation and sectioning.

Our proposed experiment aimed to test the validity of the Lorentz factor with two methods: The time of flight (TOF) of various particles at different momenta and the decay rate of pions at different momenta. Due to the high sensitivity required for the second method the results were inconclusive, therefore we report only on the results of the first method., The authors of the paper are winners of the CERN Beamline for Schools 2016 competition. To be submitted to the journal Physics Education

Surgical interventions for ocular diseases involve manipulations of semi-transparent structures in the eye, but limited visualization of these tissue layers remains a critical barrier to developing novel surgical techniques and improving clinical outcomes. We addressed limitations in image-guided ophthalmic microsurgery by using microscope-integrated multimodal intraoperative swept-source spectrally encoded scanning laser ophthalmoscopy and optical coherence tomography (iSS-SESLO-OCT). We previously demonstrated in vivo human ophthalmic imaging using SS-SESLO-OCT, which enabled simultaneous acquisition of en face SESLO images with every OCT cross-section. Here, we integrated our new 400 kHz iSS-SESLO-OCT, which used a buffered Axsun 1060 nm swept-source, with a surgical microscope and TrueVision stereoscopic viewing system to provide image-based feedback. In vivo human imaging performance was demonstrated on a healthy volunteer, and simulated surgical maneuvers were performed in ex vivo porcine eyes. Denselysampled static volumes and volumes subsampled at 10 volumes-per-second were used to visualize tissue deformations and surgical dynamics during corneal sweeps, compressions, and dissections, and retinal sweeps, compressions, and elevations. En face SESLO images enabled orientation and co-registration with the widefield surgical microscope view while OCT imaging enabled depth-resolved visualization of surgical instrument positions relative to anatomic structures-of-interest. TrueVision heads-up display allowed for side-by-side viewing of the surgical field with SESLO and OCT previews for real-time feedback, and we demonstrated novel integrated segmentation overlays for augmented-reality surgical guidance. Integration of these complementary imaging modalities may benefit surgical outcomes by enabling real-time intraoperative visualization of surgical plans, instrument positions, tissue deformations, and image-based surrogate biomarkers correlated with completion of surgical goals.