Unpaired intra-operative OCT (iOCT) video super-resolution with contrastive learning.

Regenerative therapies show promise in reversing sight loss caused by degenerative eye diseases. Their precise subretinal delivery can be facilitated by robotic systems alongside with Intra-operative Optical Coherence Tomography (iOCT). However, iOCT's real-time retinal layer information is compromised by inferior image quality. To address this limitation, we introduce an unpaired video super-resolution methodology for iOCT quality enhancement. A recurrent network is proposed to leverage temporal information from iOCT sequences, and spatial information from pre-operatively acquired OCT images. Additionally, a patchwise contrastive loss enables unpaired super-resolution. Extensive quantitative analysis demonstrates that our approach outperforms existing state-of-the-art iOCT super-resolution models. Furthermore, ablation studies showcase the importance of temporal aggregation and contrastive loss in elevating iOCT quality. A qualitative study involving expert clinicians also confirms this improvement. The comprehensive evaluation demonstrates our method's potential to enhance the iOCT image quality, thereby facilitating successful guidance for regenerative therapies.

Trocar localisation for robot-assisted vitreoretinal surgery.

PURPOSE: Robot-assisted vitreoretinal surgery provides precise and consistent operations on the back of the eye. To perform this safely, knowledge of the surgical instrument's remote centre of motion (RCM) and the location of the insertion point into the eye (trocar) is required. This enables the robot to align both positions to pivot the instrument about the trocar, thus preventing any damaging lateral forces from being exerted. METHODS: Building on a system developed in previous work, this study presents a trocar localisation method that uses a micro-camera mounted on a vitreoretinal surgical forceps, to track two ArUco markers attached on either side of a trocar. The trocar position is the estimated midpoint between the markers. RESULTS: Experimental evaluation of the trocar localisation was conducted. Results showed an RMSE of 1.82 mm for the localisation of the markers and an RMSE of 1.24 mm for the trocar localisation. CONCLUSIONS: The proposed camera-based trocar localisation presents reasonable consistency and accuracy and shows improved results compared to other current methods. Optimum accuracy for this application would necessitate a 1.4 mm absolute error margin, which corresponds to the trocar's radius. The trocar localisation results are successfully found within this margin, yet the marker localisation would require further refinement to ensure consistency of localisation within the error margin. Further work will refine these position estimates and ensure the error stays consistently within this boundary.

Reduced order modeling and model order reduction for continuum manipulators: an overview.

Soft robot's natural dynamics calls for the development of tailored modeling techniques for control. However, the high-dimensional configuration space of the geometrically exact modeling approaches for soft robots, i.e., Cosserat rod and Finite Element Methods (FEM), has been identified as a key obstacle in controller design. To address this challenge, Reduced Order Modeling (ROM), i.e., the approximation of the full-order models, and Model Order Reduction (MOR), i.e., reducing the state space dimension of a high fidelity FEM-based model, are enjoying extensive research. Although both techniques serve a similar purpose and their terms have been used interchangeably in the literature, they are different in their assumptions and implementation. This review paper provides the first in-depth survey of ROM and MOR techniques in the continuum and soft robotics landscape to aid Soft Robotics researchers in selecting computationally efficient models for their specific tasks.

Correlation Between Fundus Autofluorescence Pattern and Retinal Function on Microperimetry in Choroideremia.

Purpose: In patients with choroideremia, it is not known how smooth and mottled patterns on short-wavelength fundus autofluorescence (AF) imaging relate to retinal function. Methods: A retrospective case-note review was undertaken on 190 patients with choroideremia at two specialist centers for retinal genetics. Twenty patients with both smooth and mottled zones on short-wavelength AF imaging and concurrent mesopic microperimetry assessments were included. Mean retinal sensitivities within the smooth and mottled zones were compared between choroideremia patients, and identical points on mesopic microperimetry collected from 12 age-matched controls. Longitudinal analyses were undertaken at 2 and 5 years in a subset of patients. Results: In patients with choroideremia, mean retinal sensitivities at baseline were significantly greater in the smooth zone (26.1 ± 2.0 dB) versus the mottled zone (20.5 ± 4.2 dB) (P < 0.0001). Mean retinal sensitivities at baseline were similar in the smooth zone between choroideremia patients and controls (P = 0.054) but significantly impaired in the mottled zone in choroideremia compared to controls (P < 0.0001). The rate of decline in total sensitivity over 5 years was not significant in either the smooth or mottled zone in a small subset of choroideremia patients (n = 7; P = 0.344). Conclusions: In choroideremia, retinal sensitivity as determined by microperimetry correlates with patterns on AF imaging: retinal function in the smooth zone, where the retinal pigment epithelium is anatomically preserved, is similar to controls, but retinal sensitivity in the mottled zone is impaired. Translational Relevance: Patterns on AF imaging may represent a novel, objective outcome measure for clinical trials in choroideremia as a surrogate for retinal function.

Safety profile and surgical outcomes of early vitrectomy in eyes with unexplained fundus-obscuring vitreous haemorrhage.

OBJECTIVES: To investigate the safety profile and the surgical outcomes in a large cohort of subjects undergoing early vitrectomy for unexplained fundus-obscuring vitreous haemorrhage (FOVH). METHODS: Retrospective, single-centre case series of 186 consecutive eyes presenting between January 2018 and February 2020. Primary outcomes included change in best-corrected visual acuity (BCVA), rate of intra-operative retinal tears or retinal detachment (RD), baseline proliferative vitreoretinopathy (PVR), association of demographics with clinical outcomes, and rate of significant adverse events characterised by reoperation. RESULTS: Main final diagnosis was haemorrhagic posterior vitreous detachment (76%) and the overall risk of a retinal tear with or without RD found at the time of surgery was 69%. Vitrectomy was completed within 24 h in 94% of eyes. Rate of RD was 18%; all cases were macula-sparing with no PVR. Mean change in BCVA from baseline to final follow-up was -1.53 ± 0.69 LogMAR, p < 0.001. Time from presentation to surgery was significantly associated with final BCVA (p = 0.036, beta co-efficient 0.097). There was a significant association between presence of RD and age <60 y (OR 0.94, 95%CI [0.90-0.98], p = 0.003). 4.8% required repeated vitrectomy for post-operative RD (4), epiretinal membrane formation (3), removal of oil (1), and recurrent FOVH (1). None of these reoperations were induced by complications during the first surgery. CONCLUSION: There is a high rate of retinal breaks in cases with unexplained FOVH, and the risk of a concomitant RD is higher in younger subjects. Early vitrectomy within 24 h appears a safe first-line treatment and yields good clinical outcomes.

Surgical biomicroscopy-guided intra-operative optical coherence tomography (iOCT) image super-resolution.

PURPOSE: Intra-retinal delivery of novel sight-restoring therapies will require the precision of robotic systems accompanied by excellent visualisation of retinal layers. Intra-operative Optical Coherence Tomography (iOCT) provides cross-sectional retinal images in real time but at the cost of image quality that is insufficient for intra-retinal therapy delivery.This paper proposes a super-resolution methodology that improves iOCT image quality leveraging spatiotemporal consistency of incoming iOCT video streams. METHODS: To overcome the absence of ground truth high-resolution (HR) images, we first generate HR iOCT images by fusing spatially aligned iOCT video frames. Then, we automatically assess the quality of the HR images on key retinal layers using a deep semantic segmentation model. Finally, we use image-to-image translation models (Pix2Pix and CycleGAN) to enhance the quality of LR images via quality transfer from the estimated HR domain. RESULTS: Our proposed methodology generates iOCT images of improved quality according to both full-reference and no-reference metrics. A qualitative study with expert clinicians also confirms the improvement in the delineation of pertinent layers and in the reduction of artefacts. Furthermore, our approach outperforms conventional denoising filters and the learning-based state-of-the-art. CONCLUSIONS: The results indicate that the learning-based methods using the estimated, through our pipeline, HR domain can be used to enhance the iOCT image quality. Therefore, the proposed method can computationally augment the capabilities of iOCT imaging helping this modality support the vitreoretinal surgical interventions of the future.

Gripe-Needle: A Sticky Suction Cup Gripper Equipped Needle for Targeted Therapeutics Delivery.

This paper presents a multi-purpose gripping and incision tool-set to reduce the number of required manipulators for targeted therapeutics delivery in Minimally Invasive Surgery. We have recently proposed the use of multi-arm Concentric Tube Robots (CTR) consisting of an incision, a camera, and a gripper manipulator for deep orbital interventions, with a focus on Optic Nerve Sheath Fenestration (ONSF). The proposed prototype in this research, called Gripe-Needle, is a needle equipped with a sticky suction cup gripper capable of performing both gripping of target tissue and incision tasks in the optic nerve area by exploiting the multi-tube arrangement of a CTR for actuation of the different tool-set units. As a result, there will be no need for an independent gripper arm for an incision task. The CTR innermost tube is equipped with a needle, providing the pathway for drug delivery, and the immediate outer tube is attached to the suction cup, providing the suction pathway. Based on experiments on various materials, we observed that adding a sticky surface with bio-inspired grooves to a normal suction cup gripper has many advantages such as, 1) enhanced adhesion through material stickiness and by air-tightening the contact surface, 2) maintained adhesion despite internal pressure variations, e.g. due to the needle motion, and 3) sliding resistance. Simple Finite Element and theoretical modeling frameworks are proposed, based on which a miniature tool-set is designed to achieve the required gripping forces during ONSF. The final designs were successfully tested for accessing the optic nerve of a realistic eye phantom in a skull eye orbit, robust gripping and incision on units of a plastic bubble wrap sample, and manipulating different tissue types of porcine eye samples.

Structural and Functional Characteristics of Color Vision Changes in Choroideremia.

Color vision is considered a marker of cone function and its assessment in patients with retinal pathology is complementary to the assessments of spatial vision [best-corrected visual acuity (BCVA)] and contrast detection (perimetry). Rod-cone and chorioretinal dystrophies-such as choroideremia-typically cause alterations to color vision, making its assessment a potential outcome measure in clinical trials. However, clinical evaluation of color vision may be compromised by pathological changes to spatial vision and the visual field. The low vision Cambridge Color Test (lvCCT) was developed specifically to address these latter issues. We used the trivector version of the lvCCT to quantify color discrimination in a cohort of 53 patients with choroideremia. This test enables rapid and precise characterization of color discrimination along protan, deutan, and tritan axes more reliably than the historically preferred test for clinical trials, namely the Farnsworth Munsell 100 Hue test. The lvCCT demonstrates that color vision defects-particularly along the tritan axis-are seen early in choroideremia, and that this occurs independent of changes in visual acuity, pattern electroretinography and ellipsoid zone area on optical coherence tomography (OCT). We argue that the selective loss of tritan color discrimination can be explained by our current understanding of the machinery of color vision and the pathophysiology of choroideremia.

Design and Modelling of a Continuum Robot for Distal Lung Sampling in Mechanically Ventilated Patients in Critical Care.

In this paper, we design and develop a novel robotic bronchoscope for sampling of the distal lung in mechanically-ventilated (MV) patients in critical care units. Despite the high cost and attributable morbidity and mortality of MV patients with pneumonia which approaches 40%, sampling of the distal lung in MV patients suffering from range of lung diseases such as Covid-19 is not standardised, lacks reproducibility and requires expert operators. We propose a robotic bronchoscope that enables repeatable sampling and guidance to distal lung pathologies by overcoming significant challenges that are encountered whilst performing bronchoscopy in MV patients, namely, limited dexterity, large size of the bronchoscope obstructing ventilation, and poor anatomical registration. We have developed a robotic bronchoscope with 7 Degrees of Freedom (DoFs), an outer diameter of 4.5 mm and inner working channel of 2 mm. The prototype is a push/pull actuated continuum robot capable of dexterous manipulation inside the lung and visualisation/sampling of the distal airways. A prototype of the robot is engineered and a mechanics-based model of the robotic bronchoscope is developed. Furthermore, we develop a novel numerical solver that improves the computational efficiency of the model and facilitates the deployment of the robot. Experiments are performed to verify the design and evaluate accuracy and computational cost of the model. Results demonstrate that the model can predict the shape of the robot in <0.011s with a mean error of 1.76 cm, enabling the future deployment of a robotic bronchoscope in MV patients.

AN ASSOCIATION BETWEEN STELLATE NONHEREDITARY IDIOPATHIC FOVEOMACULAR RETINOSCHISIS, PERIPHERAL RETINOSCHISIS, AND POSTERIOR HYALOID ATTACHMENT.

PURPOSE: Stellate nonhereditary idiopathic foveomacular retinoschisis is a disorder characterized by splitting of the retina at the macula, without a known underlying mechanical or inherited cause. This study investigates demographic, anatomical, and functional characteristics of subjects with stellate nonhereditary idiopathic foveomacular retinoschisis, to explore potential underlying mechanisms. METHODS: In this single-site, retrospective, and cross-sectional, observational study, data were collected from 28 eyes from 24 subjects with stellate nonhereditary idiopathic foveomacular retinoschisis. Descriptive statistics were reported, based on the observed anatomico-functional features. RESULTS: The visual acuity remained stable (median 20/20) in all subjects over a median follow-up of 17 months. All cases demonstrated foveomacular retinoschisis within Henle's fiber layer, at the junction of the outer plexiform and outer nuclear layers. This schisis cavity extended beyond the limits of the macular OCT temporally in all eyes. In most affected eyes, there were documented features of peripheral retinoschisis and broad attachment of the posterior hyaloid at the macula. Functional testing in a cross-sectional subset demonstrated normal retinal sensitivity centrally but an absolute scotoma peripherally. CONCLUSION: Stellate nonhereditary idiopathic foveomacular retinoschisis seems to be associated with peripheral retinoschisis and anomalous or incomplete posterior hyaloid detachment. Despite chronic manifestation, this does not significantly affect central visual function but can manifest with profound loss of peripheral visual function.

Effects of the Argus II Retinal Prosthesis System on the Quality of Life of Patients With Ultra-Low Vision Due to Retinitis Pigmentosa: Protocol for a Single-Arm, Mixed Methods Study.

BACKGROUND: Retinitis pigmentosa is an incurable, degenerative retinal condition causing progressive sight loss, significantly affecting patients' quality of life. The Argus II Retinal Prosthesis is a surgically implanted medical device that delivers electrical stimulation to the retina. It is intended to produce a form of artificial vision for blind people with severe-to-profound retinitis pigmentosa by stimulating the remaining viable retinal cells to induce visual perception. This study has been initiated by National Health Service England's Commissioning through Evaluation program and funded through the National Institute of Health Research of the United Kingdom. OBJECTIVE: The aim of this study was to assess the effect of the Argus II device on patient's daily activities and quality of life. METHODS: This protocol is a prospective, single-arm, open-label, mixed methods study on 10 consecutive participants receiving the Argus II device. The patient representatives played an integral role in the design of this study. Eligibility criteria include ultra-low vision in both eyes as a result of end-stage retinitis pigmentosa and a willingness and capacity to complete the postimplantation rehabilitation program. Participants will be interviewed by independent researchers at baseline and 12 months later by using a semistructured, in-depth approach, alongside validated questionnaires (Impact of Vision Impairment-Very Low Vision, 5-level EuroQoL-5 dimensions scale, EuroQoL-visual analog scale, and Hospital Anxiety and Depression Scale) and a bespoke device-related questionnaire, which includes questions about users' experiences with the procedure, the device, and rehabilitation. The effect of the device on patients' functional vision and activities of daily living will be assessed by vision rehabilitation specialists using a set of tests measured on an ordinal scale (eg, ability to locate objects and avoid obstacles). Clinical outcomes include full-field stimulus light threshold, square localization, direction of motion, grating visual acuity, Landolt-C, procedural success, and adverse events. Qualitative and quantitative outcomes will be linked in a single database to enable individual participant measures to be considered in toto, comparing baseline to the final review. RESULTS: This study was approved by the local ethics committee on April 24, 2019 (London-Camberwell St. Giles Research Ethics Committee, reference 19/LO/0429). It has also been approved by the Health Research Authority and Health and Care Research Wales. At the time of protocol writing, Argus II was available for use in the United Kingdom; however, the manufacturer recently withdrew the Argus II device from sale in the United Kingdom. Therefore, the study is not going ahead at this time. CONCLUSIONS: The mixed methods approach provides a rich and in-depth assessment of the effect of the device on participants' quality of life. Despite the work not going ahead, the publication of this publicly funded protocol is important for researchers planning similar work. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/17436.

Dense laser at the papillomacular bundle does not cause loss of visual function.

INTRODUCTION: Juxtapapillary laser (JPL) photocoagulation in the region of the papillomacular bundle, temporal to the optic nerve, has become routine care in disorders such as optic disc pit maculopathy. Despite evidence demonstrating safe and effective use of this approach, there is still a lack of consensus in the literature, due to the perceived risk of loss of visual function. Instances of such misplaced caution could result in inadequate treatment protocols. METHODS: An observational series of five cases of optic disc pit maculopathy, treated with dense temporal juxtapapillary endolaser, in a single tertiary ophthalmic hospital. RESULTS: None of the reported cases of optic disc pit maculopathy treated with dense juxtapapillary laser demonstrated anatomical or perimetric findings consistent with nerve fiber layer damage in the region of the papillomacular bundle. CONCLUSIONS: This series demonstrates that dense laser photocoagulation, in the vicinity of the papillomacular bundle, does not cause structural damage to the nerve fiber layer or associated loss of visual function in optic disc pit maculopathy. Appropriate application of juxtapapillary laser is a safe and effective treatment for various macular pathologies.

Contemporary Outcomes and Prognostic Factors of 23-Gauge Vitrectomy for Retained Lens Fragments After Phacoemulsification.

PURPOSE: To provide data on visual acuity (VA) outcomes and prognostic factors of microincision (23-gauge) vitrectomy surgery (MIVS) for retained lens fragments after complicated cataract surgery. DESIGN: Retrospective, interventional case series from 2012 to 2017. METHODS: Precataract surgery and intraoperative (vitrectomy) parameters, postvitrectomy complications, and best-corrected visual acuities (BCVAs) were identified. Vitrectomy was performed as early as corneal clarity permitted. Univariate and multivariate logistic regression were used to characterize factors associated with achieving VA better than 20/40, or worse than 20/200 at 6 months. RESULTS: This study included 291 consecutive eyes (291 patients). LogMAR BCVA improved from 0.73 ± 0.70 before cataract surgery to 0.46 ± 0.63 (P < .001) after vitrectomy. The previtrectomy VA was 1.43 ± 0.79. At 6 months, 183 (62.9%) and 45 patients (15.5%) achieved BCVAs better than 20/40 and worse than 20/200, respectively. Most frequent complications were de novo ocular hypertension (29 eyes, 10%) and transient cystoid macular edema (25 eyes, 8.6%). Postvitrectomy retinal detachment occurred in 9 eyes (3.1%). Final VA of 20/40 or better was independently associated only with better precataract surgery VA, age <75 years, absence of preexisting diabetic macular edema (DME) or postvitrectomy persistent cystoid macular edema (P < .05). Only poorer precataract surgery VA, delaying vitrectomy to later than 2 weeks, and final aphakic status were independently predictive of 20/200 or worse VA (P < .05). CONCLUSION: Contemporary VA outcomes of 23-gauge vitrectomy for retained lens fragments are comparable with that of prior predominantly non-MIVS cohorts, but fall short of benchmarks for uncomplicated cataract surgery. IOL type or timing of placement do not impact final VA.

Deep iterative vessel segmentation in OCT angiography.

This paper addresses retinal vessel segmentation on optical coherence tomography angiography (OCT-A) images of the human retina. Our approach is motivated by the need for high precision image-guided delivery of regenerative therapies in vitreo-retinal surgery. OCT-A visualizes macular vasculature, the main landmark of the surgically targeted area, at a level of detail and spatial extent unattainable by other imaging modalities. Thus, automatic extraction of detailed vessel maps can ultimately inform surgical planning. We address the task of delineation of the Superficial Vascular Plexus in 2D Maximum Intensity Projections (MIP) of OCT-A using convolutional neural networks that iteratively refine the quality of the produced vessel segmentations. We demonstrate that the proposed approach compares favourably to alternative network baselines and graph-based methodologies through extensive experimental analysis, using data collected from 50 subjects, including both individuals that underwent surgery for structural macular abnormalities and healthy subjects. Additionally, we demonstrate generalization to 3D segmentation and narrower field-of-view OCT-A. In the future, the extracted vessel maps will be leveraged for surgical planning and semi-automated intraoperative navigation in vitreo-retinal surgery.

Learned optical flow for intra-operative tracking of the retinal fundus.

PURPOSE: Sustained delivery of regenerative retinal therapies by robotic systems requires intra-operative tracking of the retinal fundus. We propose a supervised deep convolutional neural network to densely predict semantic segmentation and optical flow of the retina as mutually supportive tasks, implicitly inpainting retinal flow information missing due to occlusion by surgical tools. METHODS: As manual annotation of optical flow is infeasible, we propose a flexible algorithm for generation of large synthetic training datasets on the basis of given intra-operative retinal images. We evaluate optical flow estimation by tracking a grid and sparsely annotated ground truth points on a benchmark of challenging real intra-operative clips obtained from an extensive internally acquired dataset encompassing representative vitreoretinal surgical cases. RESULTS: The U-Net-based network trained on the synthetic dataset is shown to generalise well to the benchmark of real surgical videos. When used to track retinal points of interest, our flow estimation outperforms variational baseline methods on clips containing tool motions which occlude the points of interest, as is routinely observed in intra-operatively recorded surgery videos. CONCLUSIONS: The results indicate that complex synthetic training datasets can be used to specifically guide optical flow estimation. Our proposed algorithm therefore lays the foundation for a robust system which can assist with intra-operative tracking of moving surgical targets even when occluded.

ADVERSE EVENTS OF THE ARGUS II RETINAL PROSTHESIS: Incidence, Causes, and Best Practices for Managing and Preventing Conjunctival Erosion.

PURPOSE: To analyze and provide an overview of the incidence, management, and prevention of conjunctival erosion in Argus II clinical trial subjects and postapproval patients. METHODS: This retrospective analysis followed the results of 274 patients treated with the Argus II Retinal Prosthesis System between June 2007 and November 2017, including 30 subjects from the US and European clinical trials, and 244 patients in the postapproval phase. Results were gathered for incidence of a serious adverse event, incidence of conjunctival erosion, occurrence sites, rates of erosion, and erosion timing. RESULTS: Overall, 60% of subjects in the clinical trial subjects versus 83% of patients in the postapproval phase did not experience device- or surgery-related serious adverse events. In the postapproval phase, conjunctival erosion had an incidence rate of 6.2% over 5 years and 11 months. In 55% of conjunctival erosion cases, erosion occurred in the inferotemporal quadrant, 25% in the superotemporal quadrant, and 20% in both. Sixty percent of the erosion events occurred in the first 15 months after implantation, and 85% within the first 2.5 years. CONCLUSION: Reducing occurrence of conjunctival erosion in patients with the Argus II Retinal Prosthesis requires identification and minimization of risk factors before and during implantation. Implementing inverted sutures at the implant tabs, use of graft material at these locations as well as Mersilene rather than nylon sutures, and accurate Tenon's and conjunctiva closure are recommended for consideration in all patients.