Robotic Navigation Autonomy for Subretinal Injection via Intelligent Real-Time Virtual iOCT Volume Slicing

In the last decade, various robotic platforms have been introduced that could support delicate retinal surgeries. Concurrently, to provide semantic understanding of the surgical area, recent advances have enabled microscope-integrated intraoperative Optical Coherent Tomography (iOCT) with high-resolution 3D imaging at near video rate. The combination of robotics and semantic understanding enables task autonomy in robotic retinal surgery, such as for subretinal injection. This procedure requires precise needle insertion for best treatment outcomes. However, merging robotic systems with iOCT introduces new challenges. These include, but are not limited to high demands on data processing rates and dynamic registration of these systems during the procedure. In this work, we propose a framework for autonomous robotic navigation for subretinal injection, based on intelligent real-time processing of iOCT volumes. Our method consists of an instrument pose estimation method, an online registration between the robotic and the iOCT system, and trajectory planning tailored for navigation to an injection target. We also introduce intelligent virtual B-scans, a volume slicing approach for rapid instrument pose estimation, which is enabled by Convolutional Neural Networks (CNNs). Our experiments on ex-vivo porcine eyes demonstrate the precision and repeatability of the method. Finally, we discuss identified challenges in this work and suggest potential solutions to further the development of such systems

Diagnosis, Treatment and Prevention of Age-Related Macular Degeneration

In this reprint, we hope to review the basics and highlight the latest developments in AMD. This demonstrates the benefits of the international scientific community working on this disease, to limit its negative impacts, the most vital of which is the loss of visual function, leading to a loss of autonomy and a decrease in patients’ quality of life

Blinding eye disease in Western Australia: perspectives on data integration

This thesis explores the utility of linked hospital administrative data for evaluating blinding eye diseases and the eye care provided for them in Western Australia. Alternative data sources and methodologies that complement linked data methods were explored. Areas of study were complications of cataract surgery, the epidemiology of blindness, diabetic retinopathy screening and management, causes of vision loss in remote Aboriginals, and the safety of intravitreal anti-vascular endothelial growth factors in age-related macular degeneration

Viral vector-mediated RNA interference in the retina

RNA interference (RNAi) is a highly conserved post-transcriptional gene silencing process triggered by double-stranded RNA (dsRNA) in eukaryotic cells. Elucidation of the RNAi regulatory pathway and its components has led to the identification of endogenous dsRNA molecules, termed microRNAs (miRNAs), which are transcribed as a single hairpin molecule prior to their maturation into a cytoplasmic dsRNA. The efficient gene silencing achieved by these short hairpin RNA (shRNA) molecules and the cumulative understanding of the RNAi pathway has prompted the development of hairpin expression vectors capable of mediating stable gene silencing in vitro and in vivo. The aim of this thesis is to evaluate the efficacy of viral vector-mediated RNAi in the retina using recombinant adeno-associated viruses (AAV) and lentiviruses that contain silencing hairpin cassettes to target four genes in murine photoreceptors and the retinal pigment epithelium (RPE). A detailed assessment of the utility and extend of RNAi in the retina using different viral vectors and hairpin designs is presented in this thesis. Lentiviral and AAV vectors were firstly used to silence GFP in vitro and in vivo as a proof of concept for vector mediated RNAi in the retina. Subsequently, we used lentivirally-mediated RNAi to study disease processes in the retina concentrating on tight junction (TJ) modulators ZO-1 and ZONAB and their role in RPE homeostasis, cell-cycle progression and epithelial-mesenchymal transition (EMT). Here we demonstrated how TJ misregulation can lead to RPE loss, proliferation or dedifferentiation; processes involved in pathological conditions such as atrophic age-related macular degeneration (AMD) and proliferative vitroretinopathy (PVR). Whilst lentivirally-mediated RNAi was used to elucidate aspects of retinal function and disease, AAV-mediated RNAi was used to probe the therapeutic potential of shRNAs by silencing Peripherin-2 (Prph2), the second most abundant retinal protein, using a miRNA-based hairpin. AAV2/8 particles were used to target endogenous Prph2 and evasion of silencing was demonstrated using an engineered Prph2 cDNA that could be used in a suppression and replacement approach for the treatment of dominant retinal disorders

A study of the retinal vascular pathology in the Royal College of Surgeons rat: A model of human retinal degeneration.

The leading causes of loss of vision in the developed world are the degenerative diseases of photoreceptors in particular, age-related macular degeneration (AMD) and retinitis pigmentosa (RP). A common characteristic of these diseases is secondary damage affecting the vascular network, which is apparently initiated by photoreceptor loss. One problem with investigating the vascular consequences of these diseases has been the lack of a suitable animal model that can be used to investigate various potential treatments. This study has developed methods of quantifying retinal vascular damage in the pigmented Royal College of Surgeons (RCS) rat, which is characterised by the formation of vascular complexes and these methods have been used to explore strategies to retard or reverse this damage. This was done with the view to improving the retinal environment, thereby assisting other therapeutic strategies that target the primary defect causing the loss of photoreceptors. The work was divided into three areas: 1) investigation of the vascular effects of progressive photoreceptor loss and development of computerised image analysis to quantify changes, 2) pharmaceutical intervention to modify the normal sequence of events, 3) examination of the effects of RPE sub-retinal transplantation on the vascular network to determine how the retinal vasculature would react to the presence of transplanted human RPE cells at different time-points. These three areas of study validate the use of naturally occurring events in the RCS rat to provide a model of vascular pathology in human retinal degenerative diseases. This contrasts with previous models, which have relied on creating wounds to simulate conditions that occurring in the diseased human retina

Visual Impairment and Blindness

Blindness and vision impairment affect at least 2.2 billion people worldwide with most individuals having a preventable vision impairment. The majority of people with vision impairment are older than 50 years, however, vision loss can affect people of all ages. Reduced eyesight can have major and long-lasting effects on all aspects of life, including daily personal activities, interacting with the community, school and work opportunities, and the ability to access public services. This book provides an overview of the effects of blindness and visual impairment in the context of the most common causes of blindness in older adults as well as children, including retinal disorders, cataracts, glaucoma, and macular or corneal degeneration