Applications In Ophthalmology Research Articles

Ocular Pharmacokinetics of Brimonidine Drug Delivery System in Monkeys and Translational Modeling for Selection of Dose and Frequency in Clinical Trials.

Brimonidine, a selective α 2-adrenoceptor agonist, displays putative retinal cyto- and neuroprotective activity in vitro and in vivo. An intravitreal sustained-release brimonidine implant, Brimonidine Posterior Segment Drug Delivery System (brimonidine DDS), allowing targeted drug delivery to the retina has been developed for potential clinical application. This study evaluates the in vivo posterior segment pharmacokinetics of brimonidine DDS implant in the monkey eye and applies translational pharmacokinetic modeling to predict tissue exposure in the human eye. Anesthetized cynomolgus monkeys received a single intravitreal injection of brimonidine DDS 400 µg implant before removal of study eyes at days 7, 30, 60, 92, 120, and 150 postimplant (three to four animals per time point) for assay of brimonidine in aqueous humor, vitreous, and retina samples. Brimonidine concentrations in the human eye were modeled using a linear, three-compartment model assuming bidirectional distribution to/from the aqueous humor and retina and elimination from the aqueous humor. Monkey tissue volumes were scaled up to human values; intercompartmental and elimination rate constants were assumed to be identical in the two species. Modeling and simulations were performed using NONMEM v. 7.3, R 3.5.1. Brimonidine exposure was highest in the monkey vitreous and retina; concentrations in the central (macula) and peripheral retina were maintained at high levels (>100 ng/g) for 3 to 4 months. Simulated brimonidine concentration-time profiles in human macula indicated that brimonidine DDS 400 µg implant would deliver effective drug concentrations (20.7‒82.2 ng/g, based on animal pharmacology) for approximately 3 months. Accordingly, administration of the 400 µg implant at 3-month intervals is recommended. SIGNIFICANCE STATEMENT: Brimonidine, an α 2-adrenoceptor agonist, is cyto- and neuroprotective in animal models of retinal/optic nerve injury. Brimonidine Posterior Segment Drug Delivery System (brimonidine DDS) is an intravitreal sustained-release implant with potential ophthalmological applications. This study explores the pharmacokinetics of brimonidine DDS 400 µg implant in the monkey eye and uses compartmental modeling to predict human ocular tissue exposure. Targeted retinal brimonidine delivery from vitreous was demonstrated in monkeys. Simulated tissue concentration-time profiles indicated persistence of pharmacologically effective brimonidine concentrations for ≈3 months in human retina.

A review of additive manufacturing applications in ophthalmology.

Additive Manufacturing (AM) capabilities in terms of product customization, manufacture of complex shape, minimal time, and low volume production those are very well suited for medical implants and biological models. AM technology permits the fabrication of physical object based on the 3D CAD model through layer by layer manufacturing method. AM use Magnetic Resonance Image (MRI), Computed Tomography (CT), and 3D scanning images and these data are converted into surface tessellation language (STL) file for fabrication. The applications of AM in ophthalmology includes diagnosis and treatment planning, customized prosthesis, implants, surgical practice/simulation, pre-operative surgical planning, fabrication of assistive tools, surgical tools, and instruments. In this article, development of AM technology in ophthalmology and its potential applications is reviewed. The aim of this study is nurturing an awareness of the engineers and ophthalmologists to enhance the ophthalmic devices and instruments. Here some of the 3D printed case examples of functional prototype and concept prototypes are carried out to understand the capabilities of this technology. This research paper explores the possibility of AM technology that can be successfully executed in the ophthalmology field for developing innovative products. This novel technique is used toward improving the quality of treatment and surgical skills by customization and pre-operative treatment planning which are more promising factors.

In vivo non-contact measurement of human iris elasticity by optical coherence elastography.

Quantifying the mechanical properties of the iris can offer valuable insights into the pathophysiology of primary angle closure glaucoma. However, current techniques for iris elastography remain ex vivo with limited clinical applications. This article describes a proposition for a non-contact and non-invasive air-puff optical coherence elastography (OCE) system that can evaluate iris elasticity in vivo. Ten eyes recruited from seven subjects underwent OCE imaging acquisition under three different illumination conditions. The Young's modulus of each eye was detected and shown to be inversely proportional to the iris length, indicating a relationship between mechanical properties and morphology of the iris. With its noninvasive and high-resolution features, this air-puff system shows great potential for applications in clinical ophthalmology.

A Ophthalmology Study on Eye Glaucoma and Retina Applied in AI and Deep Learning Techniques

Artificial intelligence based on deep learning has huge global interest in current times. Deep Learning has been widely affiliated in image and speech recognition and also natural language processing, but it is beginning of healthcare. In ophthalmology, Deep learning has applied in photographs fundus, optical coherence tomography and vision sectors. Accomplishes safety in classifying the detection performance on diabetic retinopathy, age-related macular degeneration. Deep learning may be used in concurrence with telemedicine as possible to diagnose and monitor major eye diseases for patients in primary care. There are also prospective challenges with Deep learning application in ophthalmology, including clinical and technical challenges, explain ability of the algorithm results, medico legal issues, and physician and patient acceptance of the AI “black-box” algorithms. Deep learning could probably revolutionize how ophthalmology is practiced in the future. Hence this reviewprovides a Deep Learning systems described for ophthalmic conditions, and fundamental functions.

Neuro-computational approaches for objective assessment of visual function

Retinal pathologies affect the structure and function of post-retinal visual pathways. These post-retinal alterations bear the potential to obstruct the aim of innovative retinal treatment to restore visual function. Current developments in the field of neuroimaging and the associated neurocomputational approaches enable a detailed assessment of this interrelationship. As aconsequence, they open up the possibility to anticipate the success of treatment. This review article demonstrates how innovations particularly in magnetic resonance imaging (MRI)-based anatomical, functional, and diffusion imaging can guide visual pathway assessments that are relevant for ophthalmological applications. Specific examples of retinal and visual pathway pathologies in the context of a detailed analysis of the visual pathway are described. A concept is introduced of how to translate the meaningful but technically and computationally challenging neuroimaging procedures into aclinical setting in order to effectively connect these procedures to innovative treatment approaches.

2‐Hydroxyethyl Methacrylate Hydrogels for Local Drug Delivery: Study of Topotecan and Vincristine Sorption/Desorption Kinetics and Polymer‐Drug Interaction by ATR‐FTIR Spectroscopy

AbstractPoly(2‐hydroxyethyl methacrylate) (pHEMA) hydrogels are well known in ophthalmological applications and recently investigated as drug delivery systems. The study represents a theoretical approach where the sorption/desorption experiments and spectroscopic study is used to describe the influence of the pHEMA network structure on the sorption capacity and mechanism of the release of topotecan (TPT) and vincristine (VCR). The hydrogels are synthesized by free‐radical crosslinking polymerization of HEMA monomer with ethylene glycol dimethacrylate as a crosslinker in the concentration range from 0.3 to 1 wt%. Experimental data from sorption kinetics are evaluated using sorption kinetic models and sorption isotherms, drug release mechanism is assessed by two different models and attenuated total reflectance Fourier transform infrared (ATR‐FTIR) spectroscopy is employed to describe the polymer‐drug interaction. pHEMA hydrogels exhibit higher affinity for TPT than for VCR and hydrogels prepared with 0.5 wt% of crosslinker show the maximum sorption capacity for both drugs. Physisorption is proved to be the sorption mechanism. Analyzing the FTIR spectra, it is concluded that the hydrophobic crosslinks play an important role in the interaction of the hydrogel backbone with molecules of both drugs.

Optical coherence tomography's current clinical medical and dental applications: a review.

Optical coherence tomography (OCT) is a non-invasive investigative technique that is used to obtain high-resolution three-dimensional (3D) images of biological structures. This method is useful in diagnosing diseases of specific organs like the eye, where a direct biopsy cannot be conducted. Since its inception, significant advancements have been made in its technology. Apart from its initial application in ophthalmology for retinal imaging, substantial technological innovations in OCT brought by the research community have enabled its utilization beyond its original scope and allowed its application in many new clinical areas. This review presents a summary of the clinical applications of OCT in the field of medicine (ophthalmology, cardiology, otology, and dermatology) and dentistry (tissue imaging, detection of caries, analysis of dental polymer composite restorations, imaging of root canals, and diagnosis of oral cancer). In addition, potential advantages and disadvantages of OCT are also discussed.

Solving classification problems for ordered alternatives on the example of application in ophthalmology

The aim of this study is to develop a solution to classification problems for ordered alternatives in the field of ophthalmology by the example of determining the stages of development of primary open-angle glaucoma. Materials and methods: the development of the method was carried out based on a detailed medical history of patients who were under observation at the Center for Laser Vision Restoration “Optimed”, Ufa. The database represents 793 unique patients. The main criterion for inclusion in the analysis was the diagnosis of “Primary open-angle glaucoma” (POAG) (H40.1) with the appropriate stage of the disease. The model was trained by the method of ordered regressions, in which the principle of reverse selection was used:__ all variables were included in the regression equation, and then statistically insignificant variables were excluded in the reverse order. The selection of the best model was made based on the minimum values of the information criteria Akaike, Schwartz. When analyzing the accuracy of the prediction, the conjugacy matrix was analyzed and the accuracy metric for each class was calculated. The overall accuracy metric of the classifier was defined as the weighted average of the volumes of each class represented in the test sample. Also, based on the ophthalmologists’ opinion, errors for each class were weighted by 0.9. Results: significantly associated with the stage of primary open-angle glaucoma disease were identified. The model best predicts the second stage of glaucoma. This can be justified by the size of the sample, since more than 40 percent of the sample included patients who were diagnosed with second-degree glaucoma. The overall weighted accuracy of the glaucoma stage classifier is 0.602. Conclusion: the developed solution allows you to speed up and improve the procedure for determining the stage of glaucoma but requires further improvement.

Direct generation of watt-level yellow Dy3+-doped fiber laser

Yellow lasers ( ∼ 565 – 590 nm ) are of tremendous interest in biomedicine, astronomy, spectroscopy, and display technology. So far, yellow lasers still have relied heavily on nonlinear frequency conversion of near-infrared lasers, precluding compact and low-cost yellow laser systems. Here, we address the challenge through demonstrating, for the first time, to the best of our knowledge, watt-level high-power yellow laser generation directly from a compact fiber laser. The yellow fiber laser simply consists of a Dy 3 + -doped ZBLAN fiber as gain medium, a fiber end-facet mirror with high reflectivity at yellow and a 450-nm diode laser as the pump source. We comprehensively investigated the dependence of the yellow laser performance on the output coupler reflectivity and the gain fiber length and demonstrated that the yellow fiber laser with an output coupler reflectivity of 4% and a gain fiber length of ∼ 1.8 m yields a maximum efficiency of 33.6%. A maximum output power of 1.12 W at 575 nm was achieved at a pump power of 4.20 W. This work demonstrated the power scaling of yellow Dy 3 + -doped ZBLAN fiber lasers, showing their promise for applications in ophthalmology, astronomical exploration, and high-resolution spectroscopy.

Smartphone applications in ophthalmology: A quantitative analysis.

Purpose:There is limited information in literature about the scope and usability of Smartphone Applications (Apps) in ophthalmology. Eye care professionals are therefore skeptical about the benefits of smartphone Apps and are reluctant to adopt it in their day to day practice. The purpose of this study was to provide an updated overview of all Apps exclusive to ophthalmology.Methods:This study was a quantitative analysis of Smartphone Apps exclusively designed for ophthalmic care. The Apple iPhone and Google play store were searched for eye care themed Apps. Any App related to eye treatment and management such as visual acuity screening, eye education, calculators, eBooks, Low Vision Aids were included in the study. Data on the purpose of the Apps, target end-users, validation, App usage, user ratings, and App developer qualifications were documented.Results:As of March 2020, a total of 131 Apps exclusively dedicated for eye care were identified. 53% (69/131) were available in iPhones, 44% (58/131) in Android smartphones, and 3% in both. 32% (41/131) Apps were designed for visual acuity (VA) screening, 13% (17/131) for eye relaxation exercises, 12% (15/131) for professional education, and the remaining for Apps detecting color blindness, low vision aids, and assistance and patient education. Among the 131 Apps, 6 (4.5%) Apps are claimed by the developers as validated.Conclusion:This study unveils a wide range of smartphone Apps exclusive to ophthalmology and suggests guidelines to choose an appropriate App. The study also highlights the importance of interdisciplinary collaboration in the design, development, and validation of such Apps.

Eye-Tracking for Clinical Ophthalmology with Virtual Reality (VR): A Case Study of the HTC Vive Pro Eye's Usability.

Background: A case study is proposed to empirically test and discuss the eye-tracking status-quo hardware capabilities and limitations of an off-the-shelf virtual reality (VR) headset with embedded eye-tracking for at-home ready-to-go online usability in ophthalmology applications. Methods: The eye-tracking status-quo data quality of the HTC Vive Pro Eye is investigated with novel testing specific to objective online VR perimetry. Testing was done across a wide visual field of the head-mounted-display’s (HMD) screen and in two different moving conditions. A new automatic and low-cost Raspberry Pi system is introduced for VR temporal precision testing for assessing the usability of the HTC Vive Pro Eye as an online assistance tool for visual loss. Results: The target position on the screen and head movement evidenced limitations of the eye-tracker capabilities as a perimetry assessment tool. Temporal precision testing showed the system’s latency of 58.1 milliseconds (ms), evidencing its good potential usage as a ready-to-go online assistance tool for visual loss. Conclusions: The test of the eye-tracking data quality provides novel analysis useful for testing upcoming VR headsets with embedded eye-tracking and opens discussion regarding expanding future introduction of these HMDs into patients’ homes for low-vision clinical usability.

Safety profiles of terahertz scanning in ophthalmology

Terahertz (THz) technology has emerged recently as a potential novel imaging modality in biomedical fields, including ophthalmology. However, the ocular biological responses after THz electromagnetic exposure have not been investigated. We conducted a rabbit study to evaluate the safety profiles of THz scanning on eyes, at a tissue, cellular, structural and functional level. Eight animals (16 eyes) were analysed after excessive THz exposure (control, 1 h, 4 h, and 1 week after continuous 4-h exposure; THz frequency = 0.3 THz with continuous pulse generated at 40 µW). We found that at all the time points, the corneas and lens remained clear with no corneal haze or lens opacity formation clinically and histopathologically. No thermal effect, assessed by thermographer, was observed. The rod and cone cell-mediated electroretinography responses were not significantly altered, and the corneal keratocytes activity as well as endothelial viability, assessed by in-vivo confocal microscopy, was not affected. Post-exposed corneas, lens and retinas exhibited no significant changes in the mRNA expression of heat shock protein (HSP)90AB1), DNA damage inducible transcript 3 (DDIT3), and early growth response (EGR)1. These tissues were also negative for the inflammatory (CD11b), fibrotic (fibronectin and α-smooth muscle actin), stress (HSP-47) and apoptotic (TUNEL assay) responses on the immunohistochemical analyses. The optical transmittance of corneas did not change significantly, and the inter-fibrillar distances of the corneal stroma evaluated with transmission electron microscopy were not significantly altered after THz exposure. These results provide the basis for future research work on the development of THz imaging system for its application in ophthalmology.

Femtosecond-Laser Assisted Surgery of the Eye: Overview and Impact of the Low-Energy Concept.

This article provides an overview of both established and innovative applications of femtosecond (fs)-laser-assisted surgical techniques in ophthalmology. Fs-laser technology is unique because it allows cutting tissue at very high precision inside the eye. Fs lasers are mainly used for surgery of the human cornea and lens. New areas of application in ophthalmology are on the horizon. The latest improvement is the high pulse frequency, low-energy concept; by enlarging the numerical aperture of the focusing optics, the pulse energy threshold for optical breakdown decreases, and cutting with practically no side effects is enabled.

Wearable and Implantable Intraocular Pressure Biosensors: Recent Progress and Future Prospects.

Biosensors worn on or implanted in eyes have been garnering substantial attention since being proven to be an effective means to acquire critical biomarkers for monitoring the states of ophthalmic disease, diabetes. Among these disorders, glaucoma, the second leading cause of blindness globally, usually results in irreversible blindness. Continuous intraocular pressure (IOP) monitoring is considered as an effective measure, which provides a comprehensive view of IOP changes that is beyond reach for the “snapshots” measurements by clinical tonometry. However, to satisfy the applications in ophthalmology, the development of IOP sensors are required to be prepared with biocompatible, miniature, transparent, wireless and battery‐free features, which are still challenging with many current fabrication processes. In this work, the recent advances in this field are reviewed by categorizing these devices into wearable and implantable IOP sensors. The materials and structures exploited for engineering these IOP devices are presented. Additionally, their working principle, performance, and the potential risk that materials and device architectures may pose to ocular tissue are discussed. This review should be valuable for preferable structure design, device fabrication, performance optimization, and reducing potential risk of these devices. It is significant for the development of future practical IOP sensors.

Synergistic effect in a two-phase laser procedure for production of silver nanoparticles colloids applicable in ophthalmology

This paper reports on the production of Ag nanoparticles (AgNPs) in a water solution based on a two-phase pulsed laser procedure in view of therapeutic ophthalmological applications requiring AgNPs size of ≤10 nm with a narrow size distribution. Nanoparticles of this size scale are capable of penetrating the complex ocular barriers, thus ensuring effective non-invasive drug delivery to the retina. Moreover, the ocular irritation, which is currently associated to the conventional ocular drug administration routes, would be avoided.In the first phase, AgNPs larger than 20 nm were fabricated via laser ablation of a Ag target in water by irradiation with the fundamental wavelength (λ = 1064 nm) generated by a Nd:YAG laser. During the second phase, to reduce the mean size of the as-obtained nanoparticles and properly adjust the size distribution, the water colloids were additionally irradiated with the ultraviolet harmonics (355 nm and 266 nm) of the same laser source. The effect of the key laser parameters - wavelength, fluence and laser exposure time - upon the nanoparticles morphology was studied. The most suitable post-ablation treatment of initial colloids was obtained by a consecutive irradiation with the third (λ = 355 nm) and the fourth (λ = 266 nm) harmonics of the fundamental laser wavelength. By using this approach, a synergistic effect between two mechanisms of light absorption by AgNPs was induced. As a result, contaminant-free colloids of AgNPs with sizes of less than 10 nm and quite a narrow size distribution with a standard deviation of 1.6 nm were fabricated.The toxic effect of the as-produced AgNPs on Gram-positive and Gram-negative bacteria and Candida albicans was explored. The most efficient action was reached against Pseudomonas aeruginosa and Escherichia coli.A potential application was proposed of the synthesized AgNPs colloidal aqueous solutions with antimicrobial action as a non-invasive method for ocular infections prevention and treatment.

Correction: Adaptive optics: principles and applications in ophthalmology

Correction: Adaptive optics: principles and applications in ophthalmology

Current state of artificial intelligence applications in ophthalmology and their potential to influence clinical practice

Artificial intelligence (AI) has emerged as a major frontier in healthcare and finds broad range of applications. It has the potential to revolutionize current procedures of disease diagnosis and t...

Near Infrared (NIR) Light Therapy of Eye Diseases: A Review.

Near infrared (NIR) light therapy, or photobiomodulation therapy (PBMT), has gained persistent worldwide attention in recent years as a new novel scientific approach for therapeutic applications in ophthalmology. This ongoing therapeutic adoption of NIR therapy is largely propelled by significant advances in the fields of photobiology and bioenergetics, such as the discovery of photoneuromodulation by cytochrome c oxidase and the elucidation of therapeutic biochemical processes. Upon transcranial delivery, NIR light has been shown to significantly increase cytochrome oxidase and superoxide dismutase activities which suggests its role in inducing metabolic and antioxidant beneficial effects. Furthermore, NIR light may also boost cerebral blood flow and cognitive functions in humans without adverse effects. In this review, we highlight the value of NIR therapy as a novel paradigm for treatment of visual and neurological conditions, and provide scientific evidence to support the use of NIR therapy with emphasis on molecular and cellular mechanisms in eye diseases.

Current Status of the Pharmacological Treatment of Glaucoma and Its Prospects

Glaucoma, the leading cause of blindness in adults, is a progressive neurodegenerative disease characterized by retinal ganglion cell (RGC) death. Currently, many intraocular pressure (IOP)-lowering drugs known to affect this disease progression have been developed as therapeutic agents. However, there are many cases of disease progression, even with sufficient IOP reduction. Therefore, newer therapeutic approaches other than IOP-lowering drugs are needed. To elucidate the pathogenesis of glaucoma and to develop therapeutic agents, the evaluation of RGCs is imperative, as their degeneration is the main cause of this disease. However, it is difficult to obtain RGCs from healthy individuals, let alone glaucoma patients. Therefore, research on the pathophysiology of glaucoma and drug discovery has not progressed sufficiently. Recent developments have made it possible to generate induced pluripotent stem (iPS) cells from the blood or skin of glaucoma patients and induce them to differentiate into RGCs to study the pathogenesis of glaucoma. In addition, drug repositioning for ophthalmological diseases such as glaucoma is one of the most active fields. Many of these repositioned drugs have found therapeutic applications in ophthalmology. Here, we introduce the current status of the pharmacological treatment of glaucoma and its prospects.

Research Progress of the Application of Hypothermia in the Eye.

Hypothermia is widely used in the medical field to protect organs or tissues from damage. Different research fields have different explanations of the protection mechanism of hypothermia. Hypothermia is also widely used in the field of ophthalmology, for example, in the eye bank, the preservation of corneal tissue and the preservation of the eyeball. Low temperature can also be applied to some ophthalmic diseases, such as allergic conjunctivitis, retinal ischemia, and retinal hypoxia. It is used to relieve eye symptoms or reduce tissue damage. Hypothermic techniques have important applications in ophthalmic surgery, such as corneal refractive surgery, vitrectomy surgery, and ciliary body cryotherapy for end-stage glaucoma. Hypothermia can reduce the inflammation of the cornea and protect the retinal tissue. The eyeball is a complex organ, including collagen tissue of the eyeball wall and retinal nerve tissue and retinal blood vessels. The mechanism of low temperature protecting eye tissue is complicated. It is important to understand the mechanism of hypothermia and its applications in ophthalmology. This review introduces the mechanism of hypothermia and its application in the eye banks, eye diseases (allergic conjunctivitis, retinal ischemia, and hypoxia), and eye surgeries (corneal transplant surgery, corneal refractive surgery, and vitrectomy).