The introduction of optical coherence tomography (OCT) in the 1990s revolutionized diagnostic ophthalmic imaging. Initially, OCT's role was primarily in the adult ambulatory ophthalmic clinics. Subsequent advances in handheld form factors, integration into surgical microscopes, and robotic assistance have expanded OCT's utility and impact outside of its initial environment in the adult outpatient ophthalmic clinic. In this review, we cover the use of OCT in the neonatal intensive care unit (NICU) environment with a handheld OCT, recent developments in intraoperative OCT for data visualization and measurements, and recent work and demonstration of robotically aligned OCT systems outside of eye clinics. Of note, advances in these areas are a legacy of our colleague, the late Joseph Izatt. OCT has been an important innovation for ocular diagnostics, and these advances have helped it continue to extend in new directions.

Purpose: To evaluate a recently developed technique using intraoperative optical coherence tomography (OCT) to measure subretinal tissue plasminogen activator (tPA) volumes in patients with submacular hemorrhage secondary to exudative age-related macular degeneration (AMD). Methods: Three patients (72 to 83 years old) had 25-gauge pars plana vitrectomy, subretinal tPA, and a partial gas fill. An investigational intraoperative OCT system with a modified widefield noncontact indirect viewing apparatus was used to image subretinal tPA blebs. Using the recently developed technique, the volume and surface area in the segmented region of interest were determined. Results: In each case, the delivered tPA volume measured from the syringe differed from the intraoperative OCT-measured subretinal tPA volume: Patient 1, 130 mu L from syringe, 118 mu L based on intraoperative OCT, 9% difference; Patient 2, 140 mu L, 50 mu L, 64%; Patient 3, 110 mu L, 122 mu L, 11%. The total bleb surface area was 129 mm2 in Patient 1, 55 mm2 in Patient 2, and 106 mm2 in Patient 3. Conclusions: This was the first human study to implement and evaluate intraoperative OCT image-based methods to obtain volumetric bleb measurements in patients receiving subretinal tPA for exudative AMD. This proof-of-concept study showed that intraoperative OCT-obtained bleb volume differed from intraoperative recordings, which could be explained by tPA delivery into the vitreous, efflux through the retinotomy, or human error. Intraoperative OCT can provide visualization and quantification of subretinal tPA bleb volume and surface area, which has implications for improved safety, efficacy, and analysis of the effects of subretinal drug delivery.

We demonstrate a novel, to our knowledge, approach for phase-resolved coherent 3D surface imaging that utilizes synthetic wavelength phase-based ranging and line-scan off- axis holography. Our proof-of-concept system employs an akinetic tunable laser to perform fast wavelength switching and a galvanometer mirror for slow-axis mechanical scanning. Quantitative depth measurements of an anodized aluminum plate and 3D-printed depth calibration targets and a printed circuit board are demonstrated. Analyses of both shot-noise limited system performance and speckle noise are also presented. The proof-of-concept system achieves micron-scale depth precision with a FOV of 12.8 mm x 34 mm and a 50 ms image acquisition time. (c) 2024 Optica Publishing Group. All rights, including for text and data mining (TDM), Artificial Intelligence (AI) training, and similar technologies, are reserved.

4D-microscope-integrated optical coherence tomography (4D-MIOCT) is an emergent multimodal imaging technology in which live volumetric OCT (4D-OCT) is implemented in tandem with standard stereo color microscopy. 4D-OCT provides ophthalmic surgeons with many useful visual cues not available in standard microscopy; however it is challenging for the surgeon to effectively integrate cues from simultaneous-but-separate imaging in real-time. In this work, we demonstrate progress towards solving this challenge via the fusion of data from each modality guided by segmented 3D features. In this way, a more readily interpretable visualization that combines and registers important cues from both modalities is presented to the surgeon.

Ophthalmic microsurgery is traditionally performed using stereomicroscopes and requires visualization and manipulation of sub-millimeter tissue structures with limited contrast. Optical coherence tomography (OCT) is a non-invasive imaging modality that can provide high-resolution, depth-resolved cross sections, and has become a valuable tool in clinical practice in ophthalmology. While there has been substantial progress in both research and commercialization efforts to bring OCT imaging into live surgery, its use is still somewhat limited due to factors such as low imaging speed, limited scan configurations, and suboptimal data visualization. In this paper we describe, to the best of our knowledge, the translation of the fastest swept-source intraoperative OCT system with real-time volumetric imaging with stereoscopic data visualization provided via a heads-up display into the operating room. Results from a sampling of human anterior segment and retinal surgeries chosen from 93 human surgeries using the system are shown and the benefits that this mode of intrasurgical OCT imaging provides are discussed.

Background/Purpose: Visualization of peripheral retinal structures with optical coherence tomography (OCT) can be challenging but can offer valuable clinical information. We describe a method for intraoperative OCT of the peripheral retina. Methods: An investigational microscope-integrated OCT system with real-time 4D volumetric imaging was used in conjunction with a Goldmann style mirrored contact lens intraoperatively to capture peripheral images in three patients. Results: We identified retinoschisis, a retinal break, and areas of focal retinal detachment using our peripheral OCT method. Conclusion: Use of a Goldmann lens in conjunction with intraoperative OCT offers surgeons the ability to resolve peripheral pathology that cannot be easily evaluated with OCT otherwise.

Ophthalmic microsurgery involves the manipulation of thin, semi-transparent structures and has traditionally been performed using stereoscopic microscopes that provide an en face view of the surgical field. However, new therapeutic interventions such as subretinal injections require precise tool placement and dosing that are difficult to determine from the traditional microscope view. Optical coherence tomography (OCT) provides micron scale cross-sectional imaging and has become a gold standard in clinical ophthalmology settings, but its use in surgery has been more limited. The high-speed 400 kHz intraoperative system presented here provides valuable image guidance and quantitative metrics for a variety of human surgeries.

Intraoperative optical coherence tomography (OCT) systems provide high-resolution, real-time visualization and/or guidance of microsurgical procedures. While the use of intraoperative OCT in ophthalmology has significantly improved qualitative visualization of surgical procedures inside the eye, new surgical techniques to deliver therapeutics have highlighted the lack of quantitative information available with current-generation intraoperative systems. Indirect viewing systems used for retinal surgeries introduce distortions into the resulting OCT images, making it particularly challenging to make calibrated quantitative measurements. Using an intraoperative OCT system based in part on the Leica Enfocus surgical microscope interface, we have devised novel measurement procedures, which allowed us to build optical and mathematical models to perform validation of quantitative measurements of intraocular structures for intraoperative OCT. These procedures optimize a complete optical model of the sample arm including the OCT scanner, viewing attachments, and the patient’s eye, thus obtaining the voxel pitch throughout an OCT volume and performing quantitative measurements of the dimensions of imaged objects within the operative field. We performed initial validation by measuring objects of known size in a controlled eye phantom as well as ex vivo porcine eyes. The technique was then extended to measure other objects and structures in ex vivo porcine eyes and in vivo human eyes.

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.

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:Ex vivo animal study.METHODS:Microscope-integrated optical coherence tomography was used 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 bleb 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 notably better than 4 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.