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Eye (London, England) May 2016Floaters are a common ocular condition which form as a consequence of aging changes in the vitreous. Although in most patients the symptoms are minimal, they can cause... (Review)
Review
Floaters are a common ocular condition which form as a consequence of aging changes in the vitreous. Although in most patients the symptoms are minimal, they can cause significant impairment in vision-related quality of life in a small population of patients. Recently there has been an increase in awareness of the visual disability caused by floaters, and the evidence-base for treatment of this condition using small-gauge vitrectomy has increased. In this review, we define the term 'floaters' as symptomatic vitreous opacities (SVO). We suggest a classification dependent on the presence or absence of posterior vitreous detachment and discuss their pathogenesis and natural history. We review their impact on patients' quality of life related to visual function. We review the psychological factors that may have a role in some patients who appear to be affected by SVO to the extent that they pursue all options including surgery with all its attendant risks. We summarise the available evidence-base of treatment options available for SVO with special emphasis on the safety and efficacy of vitrectomy for this condition.
Topics: Evidence-Based Medicine; Eye Diseases; Humans; Quality of Life; Vitrectomy; Vitreous Body
PubMed: 26939559
DOI: 10.1038/eye.2016.30 -
Retina (Philadelphia, Pa.) Feb 2022The causes of floaters include posterior vitreous detachment and fundus hemorrhage, both of which are risk factors for retinal tears. We observed the vitreous of...
PURPOSE
The causes of floaters include posterior vitreous detachment and fundus hemorrhage, both of which are risk factors for retinal tears. We observed the vitreous of patients with floaters using swept source optical coherence tomography.
METHODS
Fundus examination was performed, and the vitreous was observed using swept source optical coherence tomography in 202 eyes of 202 patients with floaters. Patients with uveitis, diabetic retinopathy, and other fundus diseases were excluded.
RESULTS
Swept source optical coherence tomography revealed posterior vitreous detachment in 145 of 202 eyes (71.8%) and dot reflex like stardust in the vitreous in 42 of 202 eyes (20.8%). Posterior vitreous detachment occurred in 35 of 42 eyes (83.3%) and 110 of 160 eyes (68.8%) in the stardust (+) and stardust (-) groups, respectively; a significant difference was observed (P <0.001). In the stardust (+) group, 11 of 42 eyes (26.2%) had retinal tears with posterior vitreous detachment and 21 of 42 eyes (50.0%) had fundus hemorrhage. Three of 160 eyes (1.9%) and 4 of 160 eyes (2.5%) in the stardust (-) group had retinal tears with posterior vitreous detachment and fundus hemorrhage, respectively. Both tears and fundus hemorrhage were more frequent in the stardust (+) group than in the stardust (-) group (P <0.001).
CONCLUSION
The stardust sign on swept source optical coherence tomography indicates the risk of retinal tear.
Topics: Adult; Aged; Aged, 80 and over; Female; Fundus Oculi; Humans; Male; Middle Aged; Prospective Studies; Retinal Perforations; Tomography, Optical Coherence; Vitreous Body; Vitreous Detachment; Young Adult
PubMed: 35050930
DOI: 10.1097/IAE.0000000000003317 -
Analytical and Bioanalytical Chemistry Sep 2022The stability of psychotropic substances representing various drug groups important from the perspective of forensic chemistry, including benzodiazepines,...
The stability of psychotropic substances representing various drug groups important from the perspective of forensic chemistry, including benzodiazepines, antidepressants, carbamazepine, cocaine, and their selected metabolites, was investigated for 1 month in two alternative biological matrices, vitreous humor and liver homogenate. Three different thermal storage conditions (-20, 4, and 20 °C) were tested. Liquid chromatography-mass spectrometry (LC-MS) analysis was preceded by an effective solid-phase microextraction (SPME) procedure. The results were statistically analyzed using one-way ANOVA to find significant concentration variations over time. The results obtained allowed for dividing the analytes into four groups: stable under all tested conditions, only at -20 and 4 °C, only at 20 °C, and overall unstable. Nordiazepam, venlafaxine, and cocaine and its metabolites turned out to be the most unstable substances, while fluoxetine showed the highest storage stability in both matrices. The SPME/LC-MS method was comprehensively evaluated according to the principles of white analytical chemistry (WAC), which reconcile the greenness and functionality of the method. A close to 100% whiteness score proves its sustainability and suitability for the intended application.
Topics: Chromatography, Liquid; Cocaine; Liver; Psychotropic Drugs; Solid Phase Microextraction; Vitreous Body
PubMed: 35511247
DOI: 10.1007/s00216-022-04064-w -
Investigative Ophthalmology & Visual... Feb 2024To sequence, identify, and perform phylogenetic and recombination analysis on three clinical adenovirus samples taken from the vitreous humor at the Bascom Palmer Eye...
PURPOSE
To sequence, identify, and perform phylogenetic and recombination analysis on three clinical adenovirus samples taken from the vitreous humor at the Bascom Palmer Eye Institute.
METHODS
The PacBio Sequel II was used to sequence the genomes of the three clinical adenovirus isolates. To identify the isolates, a full genome-based multiple sequence alignment (MSA) of 722 mastadenoviruses was generated using multiple alignment using fast Fourier transform (MAFFT). MAFFT was also used to generate genome-based human adenovirus B (HAdV-B) MSAs, as well as HAdV-B fiber, hexon, and penton protein-based MSAs. To examine recombination within HAdV-B, RF-Net 2 and Bootscan software programs were used.
RESULTS
In the course of classifying three new atypical ocular adenovirus samples, taken from the vitreous humor, we found that all three isolates were HAdV-B species. The three Bascom Palmer HAdV-B genomes were then combined with over 300 HAdV-B genome sequences, including nine ocular HAdV-B genome sequences. Attempts to categorize the penton, hexon, and fiber serotypes using phylogeny of the three Bascom Palmer samples were inconclusive due to incongruence between serotype and phylogeny in the dataset. Recombination analysis using a subset of HAdV-B strains to generate a hybridization network detected recombination between nonhuman primate and human-derived strains, recombination between one HAdV-B strain and the HAdV-E outgroup, and limited recombination between the B1 and B2 clades.
CONCLUSIONS
The discordance between serotype and phylogeny detected in this study suggests that the current classification system does not accurately describe the natural history and phylogenetic relationships among adenoviruses.
Topics: Humans; Animals; Adenoviridae; Vitreous Body; Phylogeny; Serogroup; Adenoviruses, Human; Hexamethonium; Recombination, Genetic
PubMed: 38319669
DOI: 10.1167/iovs.65.2.12 -
Pharmaceutical Research Jan 2019Biomarkers provide a powerful and dynamic approach to improve our understanding of the mechanisms underlying ocular diseases with applications in diagnosis, disease... (Review)
Review
Biomarkers provide a powerful and dynamic approach to improve our understanding of the mechanisms underlying ocular diseases with applications in diagnosis, disease modulation or for predicting and monitoring of clinical response to treatment. Defined as measurable indicator of normal or pathological processes, biomarker evaluation has been used extensively in drug development within clinical settings to better comprehend effectiveness of treatment in ocular diseases. Biomarkers in the eye have the advantage of access to multiple ocular matrices via minimally invasive methods. Repeat sampling for biomarker assessment has enabled reproducible objective measures of disease process or biological responses to a drug treatment. This review describes the usage of biomarkers with respect to four commonly sampled ocular matrices in clinic: tears, conjunctiva, aqueous humor and vitreous. Issues that affect the evaluation of biomarkers are discussed along with opportunities to leverage biomarkers such that ultimately, they can be used for customized targeted therapy.
Topics: Animals; Aqueous Humor; Biomarkers; Conjunctiva; Eye Diseases; Humans; Tears; Vitreous Body
PubMed: 30673862
DOI: 10.1007/s11095-019-2569-8 -
Translational Vision Science &... May 2020Although the expression of microRNAs (miRNAs) in retinal pigment epithelial (RPE) cells undergoing epithelial-mesenchymal transition (EMT) is involved in the...
PURPOSE
Although the expression of microRNAs (miRNAs) in retinal pigment epithelial (RPE) cells undergoing epithelial-mesenchymal transition (EMT) is involved in the pathogenesis of proliferative vitreoretinopathy (PVR), its expression in the vitreous of patients with primary retinal detachment (RD) and different PVR grading has not yet been investigated. We assessed the expression of miRNAs in the vitreous humor (VH) of patients diagnosed with RD and different grading of PVR.
METHODS
The VH was extracted from the core of the vitreous chamber in patients who had undergone standard vitrectomy for primary RD. RNA was extracted and TaqMan Low-Density Arrays (TLDAs) were used for miRNA profiling that was performed by single TaqMan assays. A gene ontology (GO) analysis was performed on the differentially expressed miRNAs.
RESULTS
A total of 15 eyes with RD, 3 eyes for each grade of PVR (A, B, C, and D) and 3 from unaffected individuals, were enrolled in this prospective comparative study. Twenty miRNAs were altered in the comparison among pathological groups. Interestingly, the expression of miR-143-3p, miR-224-5p, miR-361-5p, miR-452-5p, miR-486-3p, and miR-891a-5p increased with the worsening of PVR grading. We also identified 34 miRNAs showing differential expression in PVR compared to control vitreous samples. GO analysis showed that the deregulated miRNAs participate in processes previously associated with PVR pathogenesis.
CONCLUSIONS
The present pilot study suggested that dysregulated vitreal miRNAs may be considered as a biomarker of PVR and associated with the PVR-related complications in patients with RD.
TRANSLATIONAL RELEVANCE
The correlation between vitreal miRNAs and the pathological phenotypes are essential to identify the novel miRNA-based mechanisms underlying the PVR disease that would improve the diagnosis and treatment of the condition.
Topics: Humans; MicroRNAs; Pilot Projects; Prospective Studies; Retinal Detachment; Vitreoretinopathy, Proliferative; Vitreous Body
PubMed: 32821520
DOI: 10.1167/tvst.9.6.23 -
Alzheimer's Research & Therapy Sep 2020Neurofilament light chain (NfL) is a promising biomarker of neurodegeneration in the cerebrospinal fluid and blood. This study investigated the presence of NfL in the...
BACKGROUND
Neurofilament light chain (NfL) is a promising biomarker of neurodegeneration in the cerebrospinal fluid and blood. This study investigated the presence of NfL in the vitreous humor and its associations with amyloid beta, tau, inflammatory cytokines and vascular proteins, apolipoprotein E (APOE) genotypes, Mini-Mental State Examination (MMSE) scores, systemic disease, and ophthalmic diseases.
METHODS
This is a single-site, prospective, cross-sectional cohort study. Undiluted vitreous fluid (0.5-1.0 mL) was aspirated during vitrectomy, and whole blood was drawn for APOE genotyping. NfL, amyloid beta (Aβ), total Tau (t-Tau), phosphorylated Tau (p-Tau181), inflammatory cytokines, chemokines, and vascular proteins in the vitreous were quantitatively measured by immunoassay. The main outcome measures were the detection of NfL levels in the vitreous humor and its associations with the aforementioned proteins. Linear regression was used to test the associations of NfL with other proteins, APOE genotypes, MMSE scores, and ophthalmic and systemic diseases after adjustment for age, sex, education level, and other eye diseases.
RESULTS
NfL was detected in all 77 vitreous samples. NfL was not found to be associated with ophthalmic conditions, APOE genotypes, MMSE scores, or systemic disease (p > 0.05). NfL levels were positively associated with increased vitreous levels of Aβ (p = 7.7 × 10), Aβ (p = 2.8 × 10), and t-tau (p = 5.5 × 10), but not with p-tau181 (p = 0.53). NfL also had significant associations with inflammatory cytokines such as interleukin-15 (IL-15, p = 5.3 × 10), IL-16 (p = 2.2 × 10), monocyte chemoattractant protein-1 (MCP1, p = 4.1 × 10), and vascular proteins such as vascular endothelial growth factor receptor-1 (VEGFR1, p = 2.9 × 10), Vegf-C (p = 8.6 × 10), vascular cell adhesion molecule-1 (VCAM-1, p = 5.0 × 10), Tie-2 (p = 6.3 × 10), and intracellular adhesion molecular-1 (ICAM-1, p = 1.6 × 10).
CONCLUSION
NfL is detectable in the vitreous humor of the eye and significantly associated with amyloid beta, t-tau, and select inflammatory and vascular proteins in the vitreous. Additionally, NfL was not associated with patients' clinical eye condition. Our results serve as a foundation for further investigation of NfL in the ocular fluids to inform us about the potential utility of its presence in the eye.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Cross-Sectional Studies; Humans; Intermediate Filaments; Neurofilament Proteins; Prospective Studies; Vascular Endothelial Growth Factor A; Vitreous Body; tau Proteins
PubMed: 32943089
DOI: 10.1186/s13195-020-00677-4 -
System-wide vitreous proteome dissection reveals impaired sheddase activity in diabetic retinopathy.Theranostics 2022Diabetic retinopathy (DR) is a major complication of diabetes mellitus causing significant vision loss. DR is a multifactorial disease involving changes in retinal...
Diabetic retinopathy (DR) is a major complication of diabetes mellitus causing significant vision loss. DR is a multifactorial disease involving changes in retinal microvasculature and neuronal layers, and aberrations in vascular endothelial growth factors (VEGF) and inflammatory pathways. Despite the success of anti-VEGF therapy, many DR patients do not respond well to the treatment, emphasizing the involvement of other molecular players in neuronal and vascular aberrations in DR. We employed advanced mass spectrometry-based proteome profiling to obtain a global snapshot of altered protein abundances in vitreous humor from patients with proliferative DR (PDR) in comparison to individuals with epiretinal membrane without active DR or other retinal vascular complications. Global proteome correlation map and protein-protein interaction networks were used to probe into the functional inclination of proteins and aberrated molecular networks in PDR vitreous. In addition, peptide-centric analysis of the proteome data was carried out to identify proteolytic processing, primarily ectodomain shedding events in PDR vitreous. Functional validation experiments were performed using preclinical models of ocular angiogenesis. The vitreous proteome landscape revealed distinct dysregulations in several metabolic, signaling, and immune networks in PDR. Systematic analysis of altered proteins uncovered specific impairment in ectodomain shedding of several transmembrane proteins playing critical roles in neurodegeneration and angiogenesis, pointing to defects in their regulating sheddases, particularly ADAM10, which emerged as the predominant sheddase. We confirmed that ADAM10 protease activity was reduced in animal models of ocular angiogenesis and established that activation of ADAM10 can suppress endothelial cell activation and angiogenesis. Furthermore, we identified the impaired ADAM10-AXL axis as a driver of retinal angiogenesis. We demonstrate restoration of aberrant ectodomain shedding as an effective strategy for treating PDR and propose ADAM10 as an attractive therapeutic target. In all, our study uncovered impaired ectodomain shedding as a prominent feature of PDR, opening new possibilities for advancement in the DR therapeutic space.
Topics: Animals; Diabetes Mellitus; Diabetic Retinopathy; Peptide Hydrolases; Proteome; Vascular Endothelial Growth Factors; Vitreous Body
PubMed: 36185601
DOI: 10.7150/thno.72947 -
Investigative Ophthalmology & Visual... Mar 2023Age-related macular degeneration (AMD) is the leading cause of visual impairment worldwide. In this study, we aimed to investigate the vitreous humor metabolite profiles...
PURPOSE
Age-related macular degeneration (AMD) is the leading cause of visual impairment worldwide. In this study, we aimed to investigate the vitreous humor metabolite profiles of patients with intermediate AMD using untargeted metabolomics.
METHODS
We performed metabolomics using high-resolution liquid chromatography mass spectrometry on the vitreous humor of 31 patients with intermediate AMD and 30 controls who underwent vitrectomy for epiretinal membrane with or without cataract surgery. Univariate analyses after false discovery rate correction were performed to discriminate the metabolites and identify the significant metabolites of intermediate AMD. For biologic interpretation, enrichment and pathway analysis were conducted using MetaboAnalyst 5.0.
RESULTS
Of the 858 metabolites analyzed in the vitreous humor, 258 metabolites that distinguished patients with AMD from controls were identified (P values < 0.05). Ascorbic acid and uric acid levels increased in the AMD group (all P values < 0.05). The acyl carnitines, such as acetyl L-carnitine (1.37-fold), and fatty amides, such as anandamide (0.9-fold) and docosanamide (0.67-fold), were higher in patients with intermediate AMD. In contrast, nicotinamide (-0.55-fold), and succinic acid (-1.69-fold) were lower in patients with intermediate AMD. The metabolic pathway related oxidation of branched chain fatty acids and carnitine synthesis showed enrichment.
CONCLUSIONS
Multiple metabolites related to fatty amides and acyl carnitine were found to be increased in the vitreous humor of patients with intermediate AMD, whereas succinic acid and nicotinamide were reduced, suggesting that altered metabolites related to fatty amides and acyl carnitines and energy metabolism may be implicated in the etiology of AMD.
Topics: Humans; Amides; Carnitine; Macular Degeneration; Niacinamide; Succinates; Vitreous Body
PubMed: 36939720
DOI: 10.1167/iovs.64.3.28 -
Cancer Biology & Therapy 2015Uveal melanoma (UM) represents approximately 5-6% of all melanoma diagnoses and up to 50% of patients succumb to their disease. Although several methods are available,...
Uveal melanoma (UM) represents approximately 5-6% of all melanoma diagnoses and up to 50% of patients succumb to their disease. Although several methods are available, accurate diagnosis is not always easily feasible because of potential accidents (e.g., intraocular hemorrhage). Based on the assumption that the profile of circulating miRNAs is often altered in human cancers, we verified whether UM patients showed different vitreous humor (VH) or serum miRNA profiles with respect to healthy controls. By using TaqMan Low Density Arrays, we analyzed 754 miRNAs from VH, vitreal exosomes, and serum of 6 UM patients and 6 healthy donors: our data demonstrated that the UM VH profile was unique and only partially overlapping with that from serum of the same patients. Whereas, 90% of miRNAs were shared between VH and vitreal exosomes, and their alterations in UM were statistically overlapped with those of VH and vitreal exosomes, suggesting that VH alterations could result from exosomal dysregulation. We report 32 miRNAs differentially expressed in UM patients in at least 2 different types of samples analyzed. We validated these data on an independent cohort of 12 UM patients. Most alterations were common to VH and vitreal exosomes (e.g., upregulation of miR-21,-34 a,-146a). Interestingly, miR-146a was upregulated in the serum of UM patients, as well as in serum exosomes. Upregulation of miR-21 and miR-146a was also detected in formalin-fixed, paraffin-embedded UM, suggesting that VH or serum alterations in UM could be the consequence of disregulation arising from tumoral cells. Our findings suggest the possibility to detect in VH and serum of UM patients "diagnostic" miRNAs released by the affected eye: based on this, miR-146a could be considered a potential circulating marker of UM.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Case-Control Studies; Exosomes; Female; Humans; Male; Melanoma; MicroRNAs; Middle Aged; Transcriptome; Uveal Neoplasms; Vitreous Body
PubMed: 25951497
DOI: 10.1080/15384047.2015.1046021