Treatment Of Ocular Disorders Research Articles

A Vicious NGF-p75NTR Positive Feedback Loop Exacerbates the Toxic Effects of Oxidative Damage in the Human Retinal Epithelial Cell Line ARPE-19.

In spite of its variety of biological activities, the clinical exploitation of human NGF (hNGF) is currently limited to ocular pathologies. It is therefore interesting to test the effects of hNGF in preclinical models that may predict their efficacy and safety in the clinical setting of ocular disorders and compare the effects of hNGF with those of its analogs. We used a human retinal pigment cell line, ARPE-19 cells, to investigate the effects of hNGF and its analogs, mouse NGF (mNGF) and painless NGF (pNGF), on cell viability under basal conditions and after exposure to oxidative stimuli, i.e., hydrogen peroxide (H2O2) and ultraviolet (UV)-A rays. The effects of hNGF and pNGF were also tested on the gene expression and protein synthesis of the two NGF receptor subtypes, p75 neurotrophic receptors (p75NTR) and tyrosine kinase A (TrkA) receptors. We drew the following conclusions: (i) the exposure of ARPE-19 cells to H2O2 or UV-A causes a dose-dependent decrease in the number of viable cells; (ii) under baseline conditions, hNGF, but not pNGF, causes a concentration-dependent decrease in cell viability in the range of doses 1-100 ng/mL; (iii) hNGF, but not pNGF, significantly potentiates the toxic effects of H2O2 or of UV-A on ARPE-19 cells in the range of doses 1-100 ng/mL, while mNGF at the same doses presents an intermediate behavior; (iv) 100 ng/mL of hNGF triggers an increase in p75NTR expression in H2O2-treated ARPE-19 cells, while pNGF at the same dose does not; (v) pNGF, but not hNGF (both given at 100 ng/mL), increases the total cell fluorescence intensity for TrkA receptors in H2O2-treated ARPE-19 cells. The present findings suggest a vicious positive feedback loop through which NGF-mediated upregulation of p75NTR contributes to worsening the toxic effects of oxidative damage in the human retinal epithelial cell line ARPE-19. Looking at the possible clinical relevance of these findings, one can postulate that pNGF might show a better benefit/risk ratio than hNGF in the treatment of ocular disorders.

Digital Health Technologies in Vision Care: Transforming Diagnostics and Management

A significant change in the diagnosis and treatment of ocular disorders has resulted from the integration of digital health technology in the field of ophthalmology. This thorough analysis looks at the broad influence and uses of digital solutions in vision care, including wearable technology, teleophthalmology, diagnostic tools, and artificial intelligence (AI) algorithms.
 With the use of digital imaging methods like fundus photography and optical coherence tomography (OCT), physicians may now see ocular components with previously unheard-of accuracy. These imaging modalities provide early illness identification and customised treatment plans when combined with AI-driven diagnostic tools.
 Platforms for teleophthalmology provide remote screenings, consultations, and monitoring, greatly enhancing access to specialised eye care. Artificial intelligence (AI)-powered telemonitoring systems and mobile applications provide real-time data transfer for effective illness management and prompt treatments.

Pediatric Ophthalmology: Amblyopia (Lazy Eye), Strabismus, and Pediatric Eye Examinations

The preset study was conducted to review updates of the literature regarding clinical problems related to pediatric ophthalmology including amblyopia (lazy Eye), strabismus, and pediatric eye examinations. The field of pediatric ophthalmology is responsible for the discovery and treatment of vision abnormalities in children, both of which are extremely important obligations that fall under its purview. This subspecialty of pediatrics focuses on the treatment of ocular disorders in children. Both amblyopia and strabismus are prevalent disorders that, if left untreated, can have long- term negative repercussions on a person's vision. Amblyopia is more common than strabismus. The condition known as amblyopia is defined by a lack of eye movement, whereas strabismus is characterized by eyes that are turned inward. It is only via the delivery of routine eye examinations to juvenile patients that it is possible to detect these diseases as well as other abnormalities of the eye at an early stage. This not only paves the way for fast treatment but also provides the best visual outcomes that are achievable. Eye exams should be a priority for both parents and healthcare providers so that children can reach their full potential in terms of their visual development. This will allow children to attain their full potential as adults. Because of this, the child's eyes will be able to grow and develop to their full potential.

Extracellular-Vesicle-Based Therapeutics in Neuro-Ophthalmic Disorders.

Extracellular vesicles (EVs) have been recognized as promising candidates for developing novel therapeutics for a wide range of pathologies, including ocular disorders, due to their ability to deliver a diverse array of bioactive molecules, including proteins, lipids, and nucleic acids, to recipient cells. Recent studies have shown that EVs derived from various cell types, including mesenchymal stromal cells (MSCs), retinal pigment epithelium cells, and endothelial cells, have therapeutic potential in ocular disorders, such as corneal injury and diabetic retinopathy. EVs exert their effects through various mechanisms, including promoting cell survival, reducing inflammation, and inducing tissue regeneration. Furthermore, EVs have shown promise in promoting nerve regeneration in ocular diseases. In particular, EVs derived from MSCs have been demonstrated to promote axonal regeneration and functional recovery in various animal models of optic nerve injury and glaucoma. EVs contain various neurotrophic factors and cytokines that can enhance neuronal survival and regeneration, promote angiogenesis, and modulate inflammation in the retina and optic nerve. Additionally, in experimental models, the application of EVs as a delivery platform for therapeutic molecules has revealed great promise in the treatment of ocular disorders. However, the clinical translation of EV-based therapies faces several challenges, and further preclinical and clinical studies are needed to fully explore the therapeutic potential of EVs in ocular disorders and to address the challenges for their successful clinical translation. In this review, we will provide an overview of different types of EVs and their cargo, as well as the techniques used for their isolation and characterization. We will then review the preclinical and clinical studies that have explored the role of EVs in the treatment of ocular disorders, highlighting their therapeutic potential and the challenges that need to be addressed for their clinical translation. Finally, we will discuss the future directions of EV-based therapeutics in ocular disorders. Overall, this review aims to provide a comprehensive overview of the current state of the art of EV-based therapeutics in ophthalmic disorders, with a focus on their potential for nerve regeneration in ocular diseases.

Multifunctional Supramolecular Filament Hydrogel Boosts Anti‐Inflammatory Efficacy In Vitro and In Vivo

AbstractPeptide‐drug conjugates (PDCs) are an important class of therapeutic agents that combine one or more active molecules with a short peptide via a biodegradable spacer to generate prodrugs. Here an antioxidant (i.e., 3,5‐dihydroxybenzoic acid), a non‐steroidal anti‐inflammatory drug (i.e., ibuprofen, IPF), and a self‐assembled peptide motif (i.e., Gly‐Phe‐Phe‐Tyr‐Asp, GFFYD) are integrated to produce a peptide‐drug amphiphile, which self‐assembles to form hydrogel and further exerts the synergistic effects, and consequently emerges high therapeutic efficacy. In the in vitro study toward lipopolysaccharide‐activated RAW264.7 macrophages, the resulting hydrogel significantly reduces the production of cytokines (e.g., IL‐1β, IL‐6 and tumor necrosis factor‐α (i.e., TNF‐α)) compared with that of native IPF via the inhibition of nuclear factor‐κB (i.e., NF‐κB), janus kinase‐signal transducer and activator of transcription (i.e., JAK‐STAT) signals and NLR family pyrin domain containing 3 (i.e., NLRP3) inflammasome activation. Moreover, a rabbit model of endotoxin induced uveitis evidences the superior therapeutic efficacy of the resulting hydrogel over that of clinically used 0.1 wt% diclofenac sodium eyedrop. Overall, this work offers new insights into the anti‐inflammatory mechanism of PDCs hydrogel and presents the therapeutic values in the treatment of ocular disorders, and ultimately fulfils the potential clinical benefits of PDCs.

Ocular Disorders among Preschool Children in Southwest Nigeria.

PURPOSE:The aim of the study was to determine the prevalence and causes of ocular disorders among preschool children.METHODS:A multi-stage random sampling technique was used to select 560 children from a total of 9944 children aged 3–5 years attending nursery schools in the study area. Demographic and other relevant data were collected from the children. They underwent full ophthalmic evaluation including anterior and posterior segment examination as well as cycloplegic autorefraction.RESULTS:Out of the 560 children screened, 170 (30.3%) were 3 years old, 183 (32.7%) were 4 years old, while the remaining 207 (37.0%) were 5 years old. Male-to-female ratio was 1:1.1. Visual acuity was testable using Lea symbol chart in 90% of the children. Ocular disorders were found in 61 eyes of 35 children giving a prevalence of 6.3%. The most common ocular disorder among participants was refractive error (3.9%), followed by allergic conjunctivitis (1.3%). Other identified ocular disorders were strabismus (0.9%), congenital cataract (0.4%), congenital ptosis (0.4%), optic atrophy (0.4%), ectopia lentis (0.2%), and phthisis bulbi (0.2%). There was no statistically significant difference in the distribution of ocular disorders by age or gender.CONCLUSION:Screening is useful in early detection and treatment of ocular disorders in preschool children. Uncorrected refractive error which was identified as the major ocular disorder in these children is treatable. Periodic preschool vision screening would reduce the burden of uncorrected refractive error and other ocular disorders which can interfere with the learning skills of young children entering school.

Возможности применения бромфенака в офтальмологической практике

Non-steroidal anti-inflammatory drugs (NSAIDs) are essential for the treatment of ocular disorders. While corticosteroids are the gold standard for inflammatory ocular diseases, comparative studies on the efficacy of NSAIDs and corticosteroids have demonstrated no significant differences in outcomes. Given the chemical structure of NSAIDs, it should be noted that salicylates, phenamates, and pyrazoline derivatives are either toxic or unstable. Solubilizers and preservatives also account for toxicity. Bromfenac-based medications are characterized by high safety and contain minimum benzalkonium chloride. This paper reviews advantages of a modern topical NSAID, bromfenac, for ocular use. This medication is more effective than diclofenac (by 3.7 times), amfenac (by 6.5 times), and ketorolac (by 18 times) in terms of inhibiting COG-2. Furthermore, the regimen of use (twice daily), no discomfort, and excellent safety profile with minimal adverse effects improve treatment adherence. In addition, Bromfenac, a topical antiinflammatory agent, improves patients’ satisfaction with surgical outcomes since patients achieve maximum possible visual acuity as early as possible. Keywords: non-steroidal anti-inflammatory drugs, NSAIDs, bromfenac, arachidonic acid, inflammation, corticosteroids, eye surgery, cataract, cystoid macular edema. For citation: Maksimov M.L., Zvegintseva A.A., Kanner I.D., Lapkin N.M. Bromfenac in ophthalmic practice. Russian Journal of Clinical Ophthalmology. 2021;21(4):241–248 (in Russ.). DOI: 10.32364/2311-7729-2021-21-4-241-248.

Niosomal Drug Delivery Systems for Ocular Disease-Recent Advances and Future Prospects.

The eye is a complex organ consisting of several protective barriers and particular defense mechanisms. Since this organ is exposed to various infections, genetic disorders, and visual impairments it is essential to provide necessary drugs through the appropriate delivery routes and vehicles. The topical route of administration, as the most commonly used approach, maybe inefficient due to low drug bioavailability. New generation safe, effective, and targeted drug delivery systems based on nanocarriers have the capability to circumvent limitations associated with the complex anatomy of the eye. Nanotechnology, through various nanoparticles like niosomes, liposomes, micelles, dendrimers, and different polymeric vesicles play an active role in ophthalmology and ocular drug delivery systems. Niosomes, which are nano-vesicles composed of non-ionic surfactants, are emerging nanocarriers in drug delivery applications due to their solution/storage stability and cost-effectiveness. Additionally, they are biocompatible, biodegradable, flexible in structure, and suitable for loading both hydrophobic and hydrophilic drugs. These characteristics make niosomes promising nanocarriers in the treatment of ocular diseases. Hereby, we review niosome based drug delivery approaches in ophthalmology starting with different preparation methods of niosomes, drug loading/release mechanisms, characterization techniques of niosome nanocarriers and eventually successful applications in the treatment of ocular disorders.

Conjunctival bacterial flora and antimicrobial susceptibility of captive and free-living sea turtles in Brazil.

To describe the aerobic conjunctival bacterial flora of 3 especies of free-living and under human care sea turtles and determine its antimicrobial susceptibility in vitro. Thirty-six sea turtles (72 eyes), juveniles and adults, 7 free-living Chelonia mydas and 8 Chelonia mydas, 4 Caretta caretta, 11 Eretmochelys imbricata, and 6 Lepidochelys olivacea under human care, were evaluated. Conjunctival cultures were collected for identification of aerobic bacteria and antimicrobial susceptibility testing for ciprofloxacin, chloramphenicol, gentamicin, neomycin, oxacillin, polymyxin B, tetracycline, and tobramycin using antibiotic disks. Bacterial strains showing no sensitivity to 4 or more antimicrobials were considered multiresistant to this panel. Bacterial growth was observed in 12/14 (85.71%) samples in the free-living sea turtles, and there was growth in 100% (58/58) of the samples from captive animals. There were 94 strains isolated and 15 species identified. There was a predominance of Gram-positive bacteria in free-living Chelonia mydas, most of which were Bacillus and Staphylococcus. The most commonly isolated Gram-negative species were enterobacteria for free-living and under human care animals. The strains were predominantly sensitive to ciprofloxacin and tobramycin, and less sensitive to oxacillin or polymyxin B. Ten multiresistant strains were isolated. Yeast were identified in 13.89% (10/72) of the samples. These results, showing differences in the conjunctival bacterial flora of free-living and captive animals, may be helpful for diagnosis and treatment of ocular disorders in sea turtles.

Raman Microscopy: A Noninvasive Method to Visualize the Localizations of Biomolecules in the Cornea.

In vivo and in situ visualization of biomolecules without pretreatment will be important for diagnosis and treatment of ocular disorders in the future. Recently, multiphoton microscopy, based on the nonlinear interactions between molecules and photons, has been applied to reveal the localizations of various molecules in tissues. We aimed to use multimodal multiphoton microscopy to visualize the localizations of specific biomolecules in rat corneas. Multiphoton images of the corneas were obtained from nonlinear signals of coherent anti-Stokes Raman scattering, third-order sum frequency generation, and second-harmonic generation. The localizations of the adhesion complex-containing basement membrane and Bowman layer were clearly visible in the third-order sum frequency generation images. The fine structure of type I collagen was observed in the corneal stroma in the second-harmonic generation images. The localizations of lipids, proteins, and nucleic acids (DNA/RNA) was obtained in the coherent anti-Stokes Raman scattering images. Imaging technologies have progressed significantly and been applied in medical fields. Optical coherence tomography and confocal microscopy are widely used but do not provide information on the molecular structure of the cornea. By contrast, multiphoton microscopy provides information on the molecular structure of living tissues. Using this technique, we successfully visualized the localizations of various biomolecules including lipids, proteins, and nucleic acids in the cornea. We speculate that multiphoton microscopy will provide essential information on the physiological and pathological conditions of the cornea, as well as molecular localizations in tissues without pretreatment.

Evaluation of Selected Ophthalmic Diagnostic Tests in Green Iguanas (Iguana iguana)

The objective of this study was to establish reference parameters for different ophthalmic diagnostic tests in green iguanas (Iguana iguana). Median ± semi-interquartile range values of phenol red thread tear test, endodontic absorbent paper point tear test, Schirmer tear test, palpebral fissure length, and intraocular pressure were 3.9 ± 1.7mm/15seconds, 8.5 ± 2.4mm/minutes, 1.0 ± 0.5mm/minutes, 12.4 ± 1.7mm, and 18.0 ± 1.7mm Hg, respectively. Bacterial growth was observed in 18 of 20 conjunctival samples, with a predominance of Gram-positive bacteria (75.8%). Staphylococcus spp. was the most frequently isolated microorganism (39.4%), and a resistance pattern to polymyxin B was demonstrated through antimicrobial susceptibility testing of the bacterial isolates. Median ± semi-interquartile range anterior chamber depth was 1.2 ± 0.2mm and 1.4 ± 0.2mm; vitreous chamber depth, 6.8 ± 0.6mm and 6.8 ± 0.5mm; lens length, 4.4 ± 0.3mm and 4.3 ± 0.3mm; and axial globe length, 12.6 ± 0.8mm and 12.5 ± 0.7mm for the sagittal and dorsal planes, respectively. Conus papillaris length was 6.0 ± 0.3mm and 5.9 ± 0.5mm, whereas the conus papillaris width was measured at 1.1 ± 0.2mm and 1.2 ± 0.2mm, with no difference between the 4.5- and 7.5-hour planes. Hypercellular samples with dense clusters of basaloid and squamous epithelial cells were observed in the conjunctival cytological samples. These results may be helpful for diagnosis and treatment of ocular disorders in green iguanas.

Predictive Modeling of Ocular Pharmacokinetics and Adverse Effects.

Treatment of ocular disorders is a challenge due to the difficulty of delivering drugs to the target tissues within the eye at sufficient concentrations to produce a therapeutic effect. The cornea and the blood-retinal barrier, comprising of the retinal pigment epithelium and the retinal capillaries, are the main barriers for delivering drugs to treat diseases in the anterior and posterior parts of the eye, respectively. The eye has a rich blood supply and relatively small mass, and drugs can distribute from the systemic blood circulation to the choroid through the fenestrated choroidal blood vessels, but further permeation into the eye is limited by the blood-retinal barrier. Computational prediction of the ocular pharmacokinetics of drugs can help improve drug delivery and predict ocular adverse effects resulting from ocular or systemic drugs. Computational models predicting ocular adverse effects of drugs are still scarce, even though prediction of eye irritation and corrosion of chemicals has been well studied as a consequence of recent European Union legislation. Predictive modeling of adverse effects suffers from the wide distribution of data resources, but databases that integrate data on adverse effects, drugs, targets and other related biological data from different sources offer improved prospects for predictive modeling.

Stimuli-Responsive Polymeric Systems for Controlled Protein and Peptide Delivery: Future Implications for Ocular Delivery.

Therapeutic proteins and peptides have become notable in the drug delivery arena for their compatibility with the human body as well as their high potency. However, their biocompatibility and high potency does not negate the existence of challenges resulting from physicochemical properties of proteins and peptides, including large size, short half-life, capability to provoke immune responses and susceptibility to degradation. Various delivery routes and delivery systems have been utilized to improve bioavailability, patient acceptability and reduce biodegradation. The ocular route remains of great interest, particularly for responsive delivery of macromolecules due to the anatomy and physiology of the eye that makes it a sensitive and complex environment. Research in this field is slowly gaining attention as this could be the breakthrough in ocular drug delivery of macromolecules. This work reviews stimuli-responsive polymeric delivery systems, their use in the delivery of therapeutic proteins and peptides as well as examples of proteins and peptides used in the treatment of ocular disorders. Stimuli reviewed include pH, temperature, enzymes, light, ultrasound and magnetic field. In addition, it discusses the current progress in responsive ocular drug delivery. Furthermore, it explores future prospects in the use of stimuli-responsive polymers for ocular delivery of proteins and peptides. Stimuli-responsive polymers offer great potential in improving the delivery of ocular therapeutics, therefore there is a need to consider them in order to guarantee a local, sustained and ideal delivery of ocular proteins and peptides, evading tissue invasion and systemic side-effects.

Sustained-release steroids for the treatment of diabetic macular edema.

Glucocorticoids have been used for decades in the treatment of ocular disorders via topical, periocular, and more recently intravitreal routes. However, their exact mechanisms of action on ocular tissues remain imperfectly understood. Fortunately, two recently approved intravitreal sustained-release drug delivery systems have opened new perspectives for these very potent drugs. To date, among other retinal conditions, their label includes diabetic macular edema, for which a long-lasting therapeutic effect has been demonstrated both morphologically and functionally in several randomized clinical trials. The rate of ocular complications of intravitreal sustained-release steroids, mainly cataract formation and intraocular pressure elevation, is higher than with anti-vascular endothelial growth factor agents. Yet, a better understanding of the mechanisms underlying these adverse effects and the search for the minimal efficient dose should help optimize their therapeutic window.

Programa Embu Enxergando Melhor: uma proposta de atenção integral à saúde ocular em pré-escolares

OBJETIVO: A visão desempenha um papel preponderante no desenvolvimento global da criança. A detecção e o tratamento precoce de problemas visuais são fundamentais para impedir a instalação de seqüelas sensório-motoras irreversíveis. Este estudo visou descrever um programa de atenção integral à saúde ocular de crianças, constituído por ações educativas, de prevenção, de assistência e de reabilitação. MÉTODOS: Estudo descritivo transversal, no qual se utilizaram dados do treinamento dos professores, da triagem visual realizada na escola e do exame oftalmológico e ortóptico de 23.374 crianças, de cinco a sete anos de idade, matriculadas na rede municipal de educação infantil do município do Embu, no período de 1994 a 2002. RESULTADOS: Foram capacitados 600 professores e testados 22.118 (95%) pré-escolares. Destes, 4.553 (21%) precisavam de exame oftalmológico e, deles, 3.016 (66%) compareceram à consulta. Dos examinados, 1.389 (46%) receberam prescrição óptica, 477 (16%), foram encaminhadas para tratamento ortóptico e 1.601 (53%) receberam alta. CONCLUSÕES: A triagem visual é uma prática eficiente para promover a saúde ocular de pré-escolares, na qual o professor é o elemento chave. Para o êxito destas ações, é fundamental estruturar práticas educativas e de promoção da saúde ocular destinadas às crianças, às famílias e à sociedade.

A Survey of NYC Pediatric Residents Regarding Care and Management of Basic Ophthalmologic Problems

Background: In the April 2003 issue of Pediatrics the AAP issued a statement on eye examinations in children. It focused on the importance of early detection and treatment of ocular disorders in children to avoid visual impairment. This study assessed how pediatric residents feel they are equipped to handle this important responsibility and examined local residency program’s success in teaching this part of the physical exam to their residents. Methods: An anonymous survey was designed and distributed to pediatric residents in the NYC area.

Potential applications for RNAi to probe pathogenesis and develop new treatments for ocular disorders

The eye is a relatively isolated tissue compartment, which provides advantages for utilization of small interfering RNA (siRNA). Feasibility of using siRNA for treatment of choroidal neovascularization has been demonstrated using siRNA directed against vascular endothelial growth factor (VEGF) or VEGF receptor 1 (VEGFR1), and both of these approaches are being tested in clinical trials. The results with VEGFR1 siRNA show that VEGFR1 is pro-angiogenic in the eye and is not a decoy receptor as it is in developmental angiogenesis. Topical delivery of siRNAs directed against VEGF or its receptors has also been shown to suppress corneal neovascularization. Signaling through transforming growth factor-beta receptor 2 (TGFbetaR2) has been implicated in excessive ocular scarring and TGFbetaR2 siRNA has shown benefit in a model relevant to excessive scarring after glaucoma filtration surgery. RNAi has been used to identify genes that promote apoptosis or oxidative damage in retinal cells and could be the basis of new treatments for glaucoma or photoreceptor degenerations. In cultured cells derived from ocular tissues, siRNA has become a valuable tool to explore the potential role of various genes in ocular disease processes. Based upon this early experience in vivo and in vitro, it appears that siRNAs may be valuable to help define the pathogenesis and develop new treatments for several ocular diseases.

Imaging and velocimetry of the human retinal circulation with color Doppler optical coherence tomography

Noninvasive monitoring of blood flow in retinal microcirculation may elucidate the progression and treatment of ocular disorders, including diabetic retinopathy, age-related macular degeneration, and glaucoma. Color Doppler optical coherence tomography (CDOCT) is a technique that allows simultaneous micrometer-scale resolution cross-sectional imaging of tissue microstructure and blood flow in living tissues. CDOCT is demonstrated for the first time in living human subjects for bidirectional blood-flow mapping of retinal vasculature.

Botulinum toxin and its uses in the treatment of ocular disorders.

The recent utilization of type A botulinum toxin in clinical ophthalmology makes it important for all health professionals involved in eye care to understand the action of this "non-surgical" tool. This paper summarizes the present knowledge concerning the chemistry, toxicology, and pathophysiology of the toxin. It also discusses the indications, contraindications, safety, and efficacy of this use of botulinum toxin.

Two new Corticosteroid Preparations : Used in the Treatment of Ocular Disorders

Two new Corticosteroid Preparations : Used in the Treatment of Ocular Disorders