-
Drug Discovery Today Aug 2019Intravitreal injection is one of the major administration routes for the treatment of posterior ocular diseases. Intravitreal therapeutics usually suffer from... (Review)
Review
Intravitreal injection is one of the major administration routes for the treatment of posterior ocular diseases. Intravitreal therapeutics usually suffer from unsatisfactory efficacy owing to fast clearance from the vitreous humour and insufficient distribution into the retina. Engineered nanoparticles have been applied for specific tissue targeting over the past decades. In this review, we summarize the most recent research utilizing intravitreal nanoparticles to deliver therapeutics to the retina. Herein, the achievement made in preclinical research and challenges remaining in the field are highlighted. Parameters including size, charge, stability and choice of modified ligand on intraocular distribution and transport are also systematically discussed based on a proposed pharmacokinetic model. We provide insights for rational design principles for intravitreal nanoparticles for targeted retinal delivery.
Topics: Animals; Drug Delivery Systems; Humans; Intravitreal Injections; Nanoparticles; Pharmaceutical Preparations; Retina; Tissue Distribution; Vitreous Body
PubMed: 31102730
DOI: 10.1016/j.drudis.2019.05.005 -
Current Eye Research Feb 2023Intravitreal administration of drug molecules is one of the most common routes for treating posterior segment eye diseases. However, the properties of vitreous humour... (Review)
Review
Intravitreal administration of drug molecules is one of the most common routes for treating posterior segment eye diseases. However, the properties of vitreous humour changes with the time. A number of ocular complications such as liquefaction of the vitreous humour, solidification of the vitreous humour in the central vitreous cavity and detachment of the limiting membrane due to the shrinking of vitreous humour are some of the factors that can drastically affect the efficacy of therapeutics delivered via intravitreal route. Although significant research has been conducted for studying the properties of vitreous humour and its changes during the ageing process, there have been limited work to understand the effect of these changes on therapeutic efficacy of intravitreal drug delivery systems. Therefore, in this review we discussed both the coomposition and characteristics of the vitreous humour, and their subsequent influence on intravitreal drug delivery. Articles were searched on Scopus, PubMed and Web of Science up to March 2022. In this review, we discussed the biological composition and biomechanical properties of vitreous humour, methods to study the properties of vitreous humour and the changes in these properties and their relevance in ocular drug delivery field, with the aim to provide a useful insight into these aspects which can aid the process of development of novel intravitreal drug delivery systems. The composition and characteristics of the vitreous humour, and how these change during natural aging processes, directly influence intravitreal drug delivery. This review therefore highlights the importance of understanding the properties of the vitreous and identifies the need to achieve greater understanding of how changing properties of the vitreous affect the therapeutic efficacy of drugs administered for the treatment of posterior eye diseases.
Topics: Humans; Vitreous Body; Drug Delivery Systems; Eye Diseases; Pharmaceutical Preparations; Intravitreal Injections
PubMed: 36036478
DOI: 10.1080/02713683.2022.2119254 -
Journal of the Mechanical Behavior of... Oct 2022Vitreoretinal mechanics plays an important role in retinal trauma and many sight-threatening diseases. In age-related pathologies, such as posterior vitreous detachment... (Review)
Review
Vitreoretinal mechanics plays an important role in retinal trauma and many sight-threatening diseases. In age-related pathologies, such as posterior vitreous detachment and vitreomacular traction, lingering vitreoretinal adhesions can lead to macular holes, epiretinal membranes, retinal tears and detachment. In age-related macular degeneration, vitreoretinal traction has been implicated in the acceleration of the disease due to the stimulation of vascular growth factors. Despite this strong mechanobiological influence on trauma and disease in the eye, fundamental understanding of the mechanics at the vitreoretinal interface is limited. Clarification of adhesion mechanisms and the role of vitreoretinal mechanics in healthy eyes and disease is necessary to develop innovative treatments for these pathologies. In this review, we evaluate the existing literature on the structure and function of the vitreoretinal interface to gain insight into age- and region-dependent mechanisms of vitreoretinal adhesion. We explore the role of vitreoretinal adhesion in ocular pathologies to identify knowledge gaps and future research areas. Finally, we recommend future mechanics-based studies to address the critical needs in the field, increase fundamental understanding of vitreoretinal mechanisms and disease, and inform disease treatments.
Topics: Humans; Retinal Perforations; Tissue Adhesions; Vitreous Body
PubMed: 35963021
DOI: 10.1016/j.jmbbm.2022.105399 -
Macromolecular Bioscience Feb 2020Current experimental vitreous substitutes only replace the physical functions of the natural vitreous humor. Removal of the native vitreous disrupts oxygen homeostasis... (Review)
Review
Current experimental vitreous substitutes only replace the physical functions of the natural vitreous humor. Removal of the native vitreous disrupts oxygen homeostasis in the eye, causing oxidative damage to the lens that likely results in cataract formation. Neither current clinical treatments nor other experimental vitreous substitutes consider the problem of oxidative stress after vitrectomy. To address this problem, biomimetic hydrogels are prepared by free radical polymerization of poly(ethylene glycol) methacrylate and poly(ethylene glycol) diacrylate. These hydrogels have similar mechanical and optical properties to the vitreous. The hydrogels are injectable through small-gauge needles and demonstrate in vitro biocompatibility with human retinal and lens epithelial cells. The hydrogels and added vitamin C, an antioxidant, show a synergistic effect in protecting ocular cells against reactive oxygen species, which fulfills a chemical function of the natural vitreous. These hydrogels have the potential to prevent post-vitrectomy cataract formation and reduce the cost of additional surgeries.
Topics: Animals; Antioxidants; Humans; Hydrogels; Lens, Crystalline; Materials Testing; Retina; Vitreous Body
PubMed: 31846211
DOI: 10.1002/mabi.201900305 -
Retina (Philadelphia, Pa.) Jul 2021
Topics: Fovea Centralis; Humans; Male; Microscopy, Acoustic; Retinal Diseases; Tomography, Optical Coherence; Vitreous Body
PubMed: 33965994
DOI: 10.1097/IAE.0000000000003201 -
Journal of Analytical Toxicology Feb 2022Postmortem chemistry can be a useful ancillary technique that the forensic pathologist can use during a death investigation. In stark contrast, there is limited...
Postmortem chemistry can be a useful ancillary technique that the forensic pathologist can use during a death investigation. In stark contrast, there is limited information available for use of postmortem vitreous humor analysis in animals. In order to use postmortem vitreous humor in veterinary forensic investigations, validation of a method to analyze vitreous humor is required. The goal of this study was to determine the precision, bias, TEobs and sigma (σ) of the Element DC chemistry analyzer; assess its precision using the vitreous humor collected postmortem from dogs, cats and horses and assess the stability of postmortem vitreous humor from all the three species. Analysis of quality control material (QCM) and pooled vitreous humor samples for the three species was used to test for sodium (Na), chloride (Cl), potassium (K), magnesium (Mg), creatinine (Crea) and blood/vitreous urea nitrogen. Analysis of QCM showed that the Element DC was both precise and accurate. When analyzing the pooled vitreous humors, most within-run coefficients of variance (CVs) were found to be <5% and the between-run CVs for five out of six analytes were found to be <5% for dogs, cats and horses. In all the three species, the capped samples of vitreous humor were stable out of refrigeration for up to 5 h. The results of this study show that the Element DC can successfully be used to analyze the postmortem vitreous humor from dogs, cats and horses.
Topics: Animals; Autopsy; Body Fluids; Cats; Dogs; Horses; Postmortem Changes; Potassium; Sodium; Vitreous Body
PubMed: 33216118
DOI: 10.1093/jat/bkaa175 -
International Ophthalmology Jul 2023To research whether serum vascular endothelial growth factor (VEGF) levels could be used to evaluate diabetic retinopathy (DR) progression and to compare vitreous VEGF...
PURPOSE
To research whether serum vascular endothelial growth factor (VEGF) levels could be used to evaluate diabetic retinopathy (DR) progression and to compare vitreous VEGF levels after injections of intravitreal bevacizumab (IVB), ranibizumab (IVR), and triamcinolone acetonide (IVTA) in proliferative diabetic retinopathy (PDR).
METHODS
We enrolled a total of 91 eyes of 89 subjects (70 eyes of 68 diabetics and 21 eyes of 21 non-diabetic controls). The diabetic subjects were divided into three groups as PDR (n = 28), non-proliferative diabetic retinopathy (n = 20), and no-DR (n = 20). Eyes with PDR (n = 31) were injected with IVB (n = 7), IVR (n = 10), or IVTA (n = 6) 3 days before vitrectomy, and eight eyes did not receive an injection. Serum and vitreous samples were collected before vitrectomy and analyzed using ELISA.
RESULTS
We found the severity of retinopathy was not correlated with serum VEGF levels (P = .919, ρ = -0.011). Compared with the controls, vitreous VEGF was higher in the PDR (P < .001), whereas serum VEGF did not differ (P = .99). The controls had lower vitreous VEGF than the IVB, IVR, and no-injection subgroups (P = .01, P < .001, and P = .04, respectively). Vitreous VEGF was similar among the injected and no-injection subgroups (P = .17).
CONCLUSIONS
Serum VEGF levels may not directly reflect retinopathy progression. Neither IVB, IVR nor IVTA could eliminate vitreous VEGF levels within 3 days before vitrectomy.
Topics: Humans; Vascular Endothelial Growth Factor A; Diabetic Retinopathy; Vitreous Body; Bevacizumab; Ranibizumab; Vitrectomy; Enzyme-Linked Immunosorbent Assay; Diabetes Mellitus
PubMed: 36580154
DOI: 10.1007/s10792-022-02620-y -
QJM : Monthly Journal of the... Aug 2019
Topics: Diabetes Mellitus, Type 2; Eye Diseases; Humans; Male; Middle Aged; Vitreous Body
PubMed: 30690579
DOI: 10.1093/qjmed/hcz029 -
Forensic Science, Medicine, and... Sep 2023Correctly estimating the post-mortem interval (PMI) is essential in forensic practice. In recent decades, the measurement of vitreous humor analyte concentrations -...
Correctly estimating the post-mortem interval (PMI) is essential in forensic practice. In recent decades, the measurement of vitreous humor analyte concentrations - especially of hypoxanthine and potassium - and their correlation with the PMI have returned good results. However, calculating the PMI from the data collected can be quite complex. The present paper describes a web resource ( http://modestya.usc.es:3838/Forensic/ ) that simplifies the procedure. The PMI is determined (with its 95% confidence interval) in a rapid, easy, and reliable manner based on the use of mathematical models, the biochemistry of the vitreous humor, and physical variables such as the ambient temperature, the rectal temperature, and bodyweight. The application is entirely free to use.
Topics: Humans; Postmortem Changes; Autopsy; Forensic Medicine; Models, Theoretical; Vitreous Body; Potassium
PubMed: 36199004
DOI: 10.1007/s12024-022-00537-7 -
Die Ophthalmologie Jul 2022The classification of intraocular lymphomas is based on their anatomical location. They are divided into uveal lymphomas with involvement of the choroid, ciliary body or... (Review)
Review
BACKGROUND
The classification of intraocular lymphomas is based on their anatomical location. They are divided into uveal lymphomas with involvement of the choroid, ciliary body or iris and vitreoretinal lymphomas with isolated or combined involvement of the vitreous body and/or retina. Over the last decades it has become increasingly possible to work out the clinical and pathobiological features of the various subtypes, thereby reducing the diagnostic hurdles and creating improved treatment options.
OBJECTIVE
A summary of the various types of intraocular lymphoma in terms of clinical features, diagnostics, treatment and prognosis is given as well as recommendations for follow-up care.
METHODS
A selective literature search was carried out on the subject of intraocular lymphomas using PubMed and Google Scholar.
RESULTS
Intraocular lymphomas affect different structures, so that the symptoms can also be very different. The diagnostic spectrum ranges from typical ocular examination methods to sample biopsies with subsequent cytological, histological and molecular pathological processing. The treatment pillars available are percutaneous irradiation and intravitreal drug administration as local treatment and systemic treatment or a combination of systemic and local treatment. The prognosis depends mainly on the subtype of the lymphoma and the extent of the infestation when the diagnosis is confirmed. Even though some effective treatment options are now available, it has not yet been possible to significantly reduce the mortality rate.
CONCLUSION
Many different options are available for the diagnostics and treatment of intraocular lymphomas, which require close interdisciplinary cooperation. The further developments in the field of molecular pathology allow a faster and more accurate diagnosis and could open up new treatment options in the future.
Topics: Eye Neoplasms; Humans; Intraocular Lymphoma; Lymphoma; Prognosis; Vitreous Body
PubMed: 35925411
DOI: 10.1007/s00347-022-01651-1