Ophthalmic Technologies Research Articles

Oculomics: a window to the health of the body

In 2023 medical tech firm Occuity won a business start-up award from the Institute of Physics for its ground-breaking ophthalmic and disease-screening technologies. Alistair Bounds explores the power of the eye in screening for diseases and introduces the company’s work developing advanced methods to detect chronic diseases.

Retinal nerve fibre layer thinning and corneal nerve loss in patients with Bardet-Biedl syndrome

BackgroundBardet-Biedl syndrome (BBS) is an autosomal recessive, genetically heterogeneous, pleiotropic disorder caused by variants in genes involved in the function of the primary cilium. We have harnessed genomics to identify BBS and ophthalmic technologies to describe novel features of BBS.Case presentationA patient with an unclear diagnosis of syndromic type 2 diabetes mellitus, another affected sibling and unaffected siblings and parents were sequenced using DNA extracted from saliva samples. Corneal confocal microscopy (CCM) and retinal spectral domain optical coherence tomography (SD-OCT) were used to identify novel ophthalmic features in these patients. The two affected individuals had a homozygous variant in C8orf37 (p.Trp185*). SD-OCT and CCM demonstrated a marked and patchy reduction in the retinal nerve fiber layer thickness and loss of corneal nerve fibers, respectively.ConclusionThis report highlights the use of ophthalmic imaging to identify novel retinal and corneal abnormalities that extend the phenotype of BBS in a patient with syndromic type 2 diabetes.

Central fixation detection with an open-frame retinal birefringence scanning system: Optics, optomechanics, polarization balancing aspects, computer modeling and simulation

There is a growing need to add a fast fixation-detection system or even an eye-tracking system to various diagnostic and some therapeutic ophthalmic technologies. For example, this would enable registration of stable images of the fovea. In recent years we have developed rapid technologies that detect the location of the fovea using retinal birefringence scanning (RBS). Yet, combining it with ophthalmic imaging technologies is not trivial, mainly because RBS employs polarized light and polarization-sensitive optics, while most ophthalmic imaging systems do not. Therefore, integrating these two types of systems optically poses a significant challenge, especially to the RBS system. Using principles from polarization optics and Mueller-matrix-based computer modeling for optimization, we developed a prototype of an open-frame RBS system as a potential adjunct fixation monitoring technology, with a promise to reduce the interference created by eye movements in advanced ophthalmic imaging technologies, such as optical coherence tomography, fluorescein angiography, scanning laser ophthalmoscopy, and others. Our technology is fast, does not need calibration, and uses true anatomical information from the retina for fixation detection. It enables adding fixation monitoring capabilities without having to modify the main imaging system, and has the potential to facilitate imaging without anesthesia in otherwise challenging subjects and/or patients, such as young children.

Automatic Screening of Diabetic Retinopathy Using Fundus Images and Machine Learning Algorithms.

Diabetic Retinopathy is a vision impairment caused by blood vessel degeneration in the retina. It is becoming more widespread as it is linked to diabetes. Diabetic retinopathy can lead to blindness. Early detection of diabetic retinopathy by an ophthalmologist can help avoid vision loss and other complications. Diabetic retinopathy is currently diagnosed by visually recognizing irregularities on fundus pictures. This procedure, however, necessitates the use of ophthalmic imaging technologies to acquire fundus images as well as a detailed visual analysis of the stored photos, resulting in a costly and time-consuming diagnosis. The fundamental goal of this project is to create an easy-to-use machine learning model tool that can accurately predict diabetic retinopathy using pre-recorded digital fundus images. To create the suggested classifier model, we gathered annotated fundus images from publicly accessible data repositories and used two machine learning methods, support vector machine (SVM) and deep neural network (DNN). On test data, the proposed SVM model had a mean area under the receiver operating characteristic curve (AUC) of 97.11%, whereas the DNN model had a mean AUC of 99.15%.

Why Use Ultrashort Pulses in Ophthalmology and Which Factors Affect Cut Quality.

The power density of femtosecond lasers and exposure time to the tissue are crucial for a successful procedure in terms of safety and precision. The reduction of the pulse duration allows reducing the quantity of the energy to be delivered to the tissue for disruption with strongly diminished mechanical and thermal collateral damage. The cutting effect of ultra-short pulses is very precise, minimally traumatic, safe, and predictable. Future developments will lead to further energy reductions to achieve optical breakdowns. However, the pulse length cannot be shortened arbitrarily because below 100 fs nonlinear effects can change the process in an unfavorable way. Compared to manual-conventional cataract surgery, femtosecond laser-assisted cataract surgery (FLACS) shows many advantages in clinical application, especially with regard to precision and tissue protection. The femtosecond laser has become particularly important and has made the overall procedure safer when we deal with complex cataract cases such as subluxated lenses. We provide an overview of the evolution of femtosecond laser technology for use in refractive and cataract surgeries. This article describes the advantages of available laser platforms with ultrashort pulses and mainly focuses on the technical and physical backgrounds of ophthalmic surgery technologies.

Functional and structural ophthalmic imaging using noncontact multimodal photoacoustic remote sensing microscopy and optical coherence tomography

Early diagnosis of ocular diseases improves the understanding of pathophysiology and aids in accurate monitoring and effective treatment. Advanced, multimodal ocular imaging platforms play a crucial role in visualization of ocular components and provide clinicians with a valuable tool for evaluating various eye diseases. Here, for the first time we present a non-contact, multiwavelength photoacoustic remote sensing (PARS) microscopy and swept-source optical coherence tomography (SS-OCT) for in-vivo functional and structural imaging of the eye. The system provides complementary imaging contrasts of optical absorption and optical scattering, and is used for simultaneous, non-contact, in-vivo imaging of murine eye. Results of vasculature and structural imaging as well as melanin content in the retinal pigment epithelium layer are presented. Multiwavelength PARS microscopy using Stimulated Raman scattering is applied to enable in-vivo, non-contact oxygen saturation estimation in the ocular tissue. The reported work may be a major step towards clinical translation of ophthalmic technologies and has the potential to advance the diagnosis and treatment of ocular diseases.

Use of XyCAM RI for Noninvasive Visualization and Analysis of Retinal Blood Flow Dynamics During Clinical Investigations

ABSTRACT Introduction Ocular blood flow plays a critical role in eye health by nourishing the retinal and ocular tissues with oxygen and nutrients and removal of ocular metabolic waste. Imaging of retinal and optic blood flow may provide insights for early and more specific diagnoses of ocular vascular disorder and facilitate eye-based biomarkers applicable to neurological health assessment and research. Areas covered The ability of the XyCAM RI (Vasoptic Medical Inc., MD, USA) to visualize and to analyze ocular blood flow dynamics XyCAM RI using laser speckle contrast imaging is reviewed and compared with concurrent clinical ophthalmic imaging technologies like optical coherence tomography – angiography (OCT-A), fundus imaging, fluorescein angiography (FA), indocyanine green angiography (ICGA), laser Doppler flowmetry (LDF), and laser speckle flowgraphy (LSFG). Expert opinion XyCAM RI, with its unprecedented imaging capabilities to assess blood flow dynamics provides a powerful tool to ophthalmic researchers and doctors to obtain greater clinical insights into the physiological status of the posterior segment and treatment approaches for various diseases in a very patient-friendly, noninvasive manner, unlike dye-based angiographic techniques such as FA or ICG. XyCAM RI is well suited as a modality that could close the gap between current screening and comprehensive eye exams.

A study to identify limitations of existing automated systems to detect glaucoma at initial and curable stage

AbstractGlaucoma ocular disease is the second topmost reason for irreversible visual impairment around the world. This malady can be cured and permanent blindness can be prevented by timely diagnosis and treatment. This study is an attempt to analyse the current status of automated glaucoma diagnosis systems. Existing systems have been analysed on the base of ophthalmic imaging technology, capability to detect glaucoma at initial or latter stages, detection strategy and performance. Analysis revealed several research gaps mainly in automated glaucoma detection based on Fundus and Optical Coherence Tomography (OCT) ophthalmic imaging technologies. More accurate diagnosis of glaucoma at early and curable stages is possible by bridging the identified gaps.

Retinal changes in Alzheimer's disease- integrated prospects of imaging, functional and molecular advances.

Alzheimer's Disease (AD) is a devastating neurodegenerative disorder of the brain, clinically characterised by cognitive deficits that gradually worsen over time. There is, at present, no established cure, or disease-modifying treatments for AD. As life expectancy increases globally, the number of individuals suffering from the disease is projected to increase substantially. Cumulative evidence indicates that AD neuropathological process is initiated several years, if not decades, before clinical signs are evident in patients, and diagnosis made. While several imaging, cognitive, CSF and blood-based biomarkers have been proposed for the early detection of AD; their sensitivity and specificity in the symptomatic stages is highly variable and it is difficult to justify their use in even earlier, pre-clinical stages of the disease. Research has identified potentially measurable functional, structural, metabolic and vascular changes in the retina during early stages of AD. Retina offers a distinctively accessible insight into brain pathology and current and developing ophthalmic technologies have provided us with the possibility of detecting and characterising subtle, disease-related changes. Recent human and animal model studies have further provided mechanistic insights into the biochemical pathways that are altered in the retina in disease, including amyloid and tau deposition. This information coupled with advances in molecular imaging has allowed attempts to monitor biochemical changes and protein aggregation pathology in the retina in AD. This review summarises the existing knowledge that informs our understanding of the impact of AD on the retina and highlights some of the gaps that need to be addressed. Future research will integrate molecular imaging innovation with functional and structural changes to enhance our knowledge of the AD pathophysiological mechanisms and establish the utility of monitoring retinal changes as a potential biomarker for AD.

HTLV-1 in Ophthalmology.

Human T-cell leukemia virus type 1 (HTLV-1) was the first retrovirus described as a causative agent for human disease. In the field of ophthalmology, a close relationship between HTLV-1 infection and uveitis was identified through a series of clinical and laboratory studies in the late 1980s–1990s. Since then, HTLV-1-related ocular manifestations such as keratoconjunctivitis sicca, interstitial keratitis, optic neuritis and adult T-cell leukemia/lymphoma (ATL)-related ocular manifestations have continuously been reported. During the three decades since the association between HTLV-1 and ocular pathologies was discovered, ophthalmic practice and research have advanced with the incorporation of new technologies into the field of ophthalmology. Accordingly, new findings from recent research have provided many insights into HTLV-1-associated ocular diseases. Advanced molecular technologies such as multiplex polymerase chain reaction (PCR)/broad-range PCR using ocular samples have enabled rapid and accurate diagnosis. Advanced ophthalmic technologies such as widefield fundus camera and optical coherence tomography (OCT) have clarified various features of HTLV-1-associated ocular manifestations, and identified characteristics such as the “knob-like ATL cell multiple ocular infiltration” (KAMOI) sign. Advanced drug delivery methods such as intravitreal injection and sub-Tenon injection have led to progress in preventing disease progression. This article describes global topics and the latest research findings for HTLV-1-associated ocular diseases, with reference to a large-scale nationwide survey of ophthalmologists. Current approaches and unmet needs for HTLV-1 infection in ophthalmology are also discussed.

Computer-aided fixation detection using retinal birefringence in multi-modal ophthalmic systems: Computer, electronics, algorithms

Many diagnostic and some therapeutic ophthalmic devices require a reliable complementing method to track the direction of gaze or just to validate fixation of the eye on a presented target. This would allow acquisition of artefact-free robust images of the fovea and the surrounding macula. So far, there have been only few attempts to provide fast and dependable fixation information to an optical imaging system in real time, to guide image acquisition. The author's lab has developed several instruments that detect the location of the fovea using retinal birefringence scanning (RBS), proven to be very effective. Here, an RBS-based fixation detection subsystem is proposed, designed to operate conjointly with a number of ophthalmic imaging technologies. Combining RBS with such technologies is not trivial, because RBS uses polarized light and polarization-sensitive optics, while most other modalities don't. The polarization optics was optimized by means of enhanced computer modeling. Both the electronic hardware and the software were designed for fast and reliable performance. Because many retinal imaging systems are used in pediatric settings, extensive audio-visual circuitry was employed for efficient attention/fixation attraction. The optomechanics has been optimized for robust data acquisition. This computer-aided conjoint system employs true anatomical information from the back of the eye and needs no calibration. The prototype instrument uses a decision-making logic based on four frequencies generated during scanning. The results reveal the applicability of RBS as an adjunct fixation monitoring modality, showing promise to remove the limitation imposed by eye movements upon advanced ophthalmic imaging technologies.

Automatic Annotation of Retinal Layers in Optical Coherence Tomography Images

Early diagnosis of retinal OCT images has been shown to curtail blindness and visual impairments. However, the advancement of ophthalmic imaging technologies produces an ever-growing scale of retina images, both in volume and variety, which overwhelms the ophthalmologist ability to segment these images. While many automated methods exist, speckle noise and intensity inhomogeneity negatively impacts the performance of these methods. We present a comprehensive and fully automatic method for annotation of retinal layers in OCT images comprising of fuzzy histogram hyperbolisation (FHH) and graph cut methods to segment 7 retinal layers across 8 boundaries. The FHH handles speckle noise and inhomogeneity in the preprocessing step. Then the normalised vertical image gradient, and it’s inverse to represent image intensity in calculating two adjacency matrices and then the FHH reassigns the edge-weights to make edges along retinal boundaries have a low cost, and graph cut method identifies the shortest-paths (layer boundaries). The method is evaluated on 150 B-Scan images, 50 each from the temporal, foveal and nasal regions were used in our study. Promising experimental results have been achieved with high tolerance and adaptability to contour variance and pathological inconsistency of the retinal layers in all (temporal, foveal and nasal) regions. The method also achieves high accuracy, sensitivity, and Dice score of 0.98360, 0.9692 and 0.9712, respectively in segmenting the retinal nerve fibre layer. The annotation can facilitate eye examination by providing accurate results. The integration of the vertical gradients into the graph cut framework, which captures the unique characteristics of retinal structures, is particularly useful in finding the actual minimum paths across multiple retinal layer boundaries. Prior knowledge plays an integral role in image segmentation.

Visual and physiological optics: introduction to the Journal of the Optical Society of America A feature issue.

The 9th European Meeting on Visual Physiological Optics (VPO2018) was held August 29-31, 2018, in Athens, Greece. This issue of the Journal of the Optical Society of America A (JOSA A) is a dedicated feature, including numerous articles that span a large range of visual optics related topics, ranging from geometrical optics to visual psychophysics and from optical metrology to ophthalmic diagnostic technologies. The next VPO meeting will be held August 2020 in Cambridge, UK.

How to improve Iranians' vision health: on the national policy of preventing Iranians' blindness.

To review vision health situation of Iranian community, analyze its determinants, and discuss the adopted improvement strategies by the Iran Ministry of Health and Medical Education (MOHME). This was a rapid situation analysis with a qualitative approach in three parts of recognition, orientation and implementation. The data were gathered via review of upstream documents, national and international experiences, and experts and stakeholders' opinions. Eradicating trachoma, increasing human resources, increasing educational and research centers and promotion of ophthalmic technologies were important achievements in the field of vision health in Iran. Through these achievements, it seemed that the pattern of causes of blindness and low vision was similar to that of the developed countries. However, the review of Iranians' vision health indicators showed that a considerable percent of the blindness and low vision was avoidable through a national program demanding 3 types of interventions in social determinants of health (SDH), community education, and increasing the access to health care services by integrating the necessary services in primary health care system. Managing the issue requires attentions from a national committee for preventing blindness with participation of all stakeholders, implementing a national survey on vision health, preparation of the primary level health centers including employment and education of community health workers (Behvarzes), optometrists and general practitioners, fair distribution of specialized human resources and establishing at least one specialized center in each province for referring patients from the primary levels.

Ocular Drug Delivery System-An Update Review

Eye being a unique and complex organ the access of exogenous substances to the ocular tissues are restricted by its physiology and defense mechanism. Thus the delivery of therapeutic agents to the ocular tissues is not an easy assignment. Cornea an important component present in eye is protected by very effective protective mechanisms which provide the pharmaceutical scientists a challenge of designing a formulation and delivering it to the targeted sites in sufficient concentrations. Development of newer approaches and novel therapeutic agents continue to provide delivery system a high therapeutic efficacy. Due to the defects in the traditional treatment, and also the therapeutic drug levels in targeted site is not maintained for longer time, the search of new type of ophthalmic approaches and technologies has drawn more and more attentions. In past two decades research in ocular delivery system have been accelerated towards a novel, safe and patient compliance formulation and medical devices to surpass the barriers and maintain the therapeutic level in tissues. Recently various technologies with good efficacy and biocompatibility have also been developed to treat the ocular diseases at both the anterior and posterior portion of eye. Anterior segment approaches for ocular treatment, advances are witnessed through the modulation of conventional topical drops with permeation enhancers and it also includes the development as ointments, gels etc. Several nano-formulations are also introduced for treating the anterior portion of the eye. Furthermore for posterior delivery, research focused immensely towards the development of releasing devices and also nano-formulation. Therefore these novel approaches and devices are easy to formulate, possess negligible irritation, prolonged precorneal residence time, sustained drug release, and enhanced bioavailability. An update of research advancement in ocular drug delivery provides and helps the scientists to modulate and develop safe drug delivery strategies. This review article gives update information about various approaches for delivering the drug to ocular region.

The role of ophthalmic imaging in central nervous system degeneration in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disorder that can involve any organ system. Central nervous system involvement can be a severe life threatening complication, ultimately resulting in severe neurodegenerative changes. Magnetic resonance imaging suggests that neurodegeneration, which may have deleterious effects on brain function, may occur early in SLE and experimental models suggest that neuroprotection may be feasible and beneficial. The retina is an extension of the brain. Recent ophthalmic imaging technologies are capable of identifying early changes in retinal and choroidal morphology and circulation that may reflect CNS degeneration. However, their utility in monitoring CNS involvement in SLE has been poorly studied as these have only been performed in small cohorts, in a cross-sectional design, non-quantitatively and without correlation to disease activity. The authors aim to review the current understanding of neurodegeneration associated with SLE, with particular focus on the visual pathway. We describe the neuropathology of the visual system in SLE and the evidence for retinal and choroidal neurodegenerative and microvascular changes using optical coherence tomography technology. We aim to describe the potential role of optical imaging modalities in NPSLE diagnosis and their likely impact on the study of neuronal function.

Technical principles of adaptive optics in ophthalmology

During the last 25years ophthalmic imaging has undergone arevolution. This review gives an overview of the possibilities of adaptive optics (AO) for ophthalmic imaging technologies and their development and illustrates that the role of ophthalmic imaging changed from the documentation of obvious abnormalities to the detection of microscopic yet significant conspicuities. This enables earlier and more precise diagnoses. The implementation of AO for imaging systems like fundus cameras, scanning laser ophthalmoscopy and optical coherence tomography has gained in importance. In recent years acouple of companies started developing commercially available AO systems, thus, indicating afuture use in clinical routine.

The Implantable Miniature Telescope and Quality of Life Improvements in Patients with End-Stage Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a progressive, degenerative eye disease that leads to central vision loss in people older than 60. End-stage AMD, for which there is no cure, is the leading cause of blindness in highincome countries. Often underappreciated by physicians, AMD is an important public health problem as patients can experience significant emotional distress, reduced cognitive function and a decrease in quality of life from depression, isolation, reduced mobility, and independence. These patients are more likely to suffer from falls and injuries, which may result in serious, life-threatening complications and significant medical costs. There are no medical interventions that can halt the visual outcome of end-stage AMD; patients can only make the best of the vision they have left through low-vision rehabilitation and external devices and tools. In 2010, the U.S. Food and Drug Administration approved the implantable miniature telescope (IMT; VisionCare Ophthalmic Technologies, Saratoga, CA) prosthesis for severely visually impaired patients with bilateral end-stage AMD. Patients with no other treatment options may have improved quality of life after implantation due to visual gains, increased mobility and independence, and improved overall function.

Telemedicine for ophthalmic consultation services: use of a portable device and layering information for graders

Introduction We compared remote, image-based patient consultations to in-person consultations at emergency department and inpatient hospital settings. Methods Patients evaluated by the ophthalmic consultation services (gold standard) were imaged over a two-week period. A trained study coordinator took anterior segment photographs (AS) and posterior segment photographs (PS) with a portable camera (PictorPlus, Volk Optical, Cleveland, OH). Ophthalmologists (graders) determined photograph quality, presence of pathology, and their confidence in disease detection. At a separate session, graders reassessed photographs accompanied by a one-sentence summary of demographics and chief complaint (CHx). We computed accuracy and reliability statistics. Results We took AS photographs of 24 eyes of 15 patients and PS photographs of 39 eyes of 20 patients. The majority of images were rated as acceptable or excellent in quality (AS: 89–96%; PS: 70–75%). Graders detected AS pathology with 62–81% sensitivity based on photographs, increasing to 87–88% sensitivity with photographs plus CHx. Graders detected PS pathology with 79–86% sensitivity based on a photograph only, increasing to 100% sensitivity with photographs plus CHx. Discussion In this pilot study, there is evidence that portable ophthalmic imaging technologies could enable ophthalmologists to remotely evaluate anterior and posterior segment eye diseases with good sensitivity. The ophthalmologist could detect ocular pathology on photographs more accurately if they were provided brief clinical information.

Does this child have glaucoma or something else? Applying newer technologies to the diagnosis and management of pediatric glaucoma

The workshop is designed to highlight the sometimes challenging clinical entity of the “glaucoma suspect,” with emphasis on newer ophthalmic technologies and how they may assist in our diagnostic evaluation of these cases. Medication update and pearls for use in children will be included.