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International Ophthalmology Feb 2020To explore the relationships between the aqueous and vitreous levels of vascular endothelial growth factor-A (VEGF-A), interleukin-8 (IL-8), placental growth factor...
PURPOSE
To explore the relationships between the aqueous and vitreous levels of vascular endothelial growth factor-A (VEGF-A), interleukin-8 (IL-8), placental growth factor (PlGF) and erythropoietin (EPO) in proliferative diabetic retinopathy (PDR) and neovascular glaucoma (NVG).
METHODS
Aqueous and vitreous samples were obtained from patients with PDR and NVG during surgery. Aqueous and vitreous concentrations of VEGF-A, IL-8, PlGF and EPO were measured via enzyme-linked immunosorbent assay.
RESULTS
No correlation between the aqueous and vitreous levels of VEGF-A, IL-8, PlGF or EPO was found in both the PDR and the NVG eyes. Aqueous VEGF-A was significantly higher in the NVG group (317.55 ± 36.25 pg/ml, n = 15) than that in the PDR group (256.23 ± 46.11 pg/ml, n = 17, P < 0.001). The level of VEGF-A in aqueous (317.55 ± 36.25 pg/ml, n = 15) was significantly higher than that in vitreous (224.74 ± 60.32 pg/ml, n = 15, P < 0.001) in NVG patients. The level of IL-8 in aqueous (76.55 ± 10.88 pg/ml, n = 17) was significantly higher than that in vitreous (63.55 ± 10.74 pg/ml, n = 17, P = 0.001) in PDR patients. The level of EPO in aqueous (18.62 ± 2.87 mIU/ml, n = 15) was significantly higher than that in vitreous (15.97 ± 3.11 mIU/ml, n = 15, P = 0.022) in NVG patients. The ratio of aqueous versus vitreous for VEGF-A was significantly higher in the NVG group (1.475 ± 0.289, n = 15) than that in the PDR group (0.996 ± 0.227, n = 17, P < 0.001).
CONCLUSION
Aqueous levels of VEGF-A, IL-8, PlGF and EPO do not correlate with vitreous levels of those proteins. The relationship between protein levels in aqueous humor and vitreous might be dependent on different disease status or protein types investigated.
Topics: Adult; Aged; Aqueous Humor; Biomarkers; Diabetic Retinopathy; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Glaucoma, Neovascular; Humans; Male; Middle Aged; Placenta Growth Factor; Vascular Endothelial Growth Factor A; Vitreous Body
PubMed: 31802372
DOI: 10.1007/s10792-019-01207-4 -
Forensic Science International Feb 2022This study aimed to compare the frequency of postmortem ethanol formation in blood, urine and vitreous humor according to negative ethylsulphate (EtS) in blood or...
PURPOSE
This study aimed to compare the frequency of postmortem ethanol formation in blood, urine and vitreous humor according to negative ethylsulphate (EtS) in blood or positive putrefactive alcohols (PA's) in either medium. Furthermore, it aimed to evaluate the interpretational value of calculated ethanol ratios in relation to EtS and PA results.
METHODS
Blood ethanol positive forensic cases were included; one dataset consisting of 2504 cases with EtS analysed in blood and another dataset with 8001 cases where PA's were analysed.
RESULTS
PA's were found in 24.4% of cases. EtS was negative in 15.3%, 9.4% and 7.4% of cases that were positive for ethanol in blood, urine and vitreous humor, respectively. In EtS negative cases, the concentrations of ethanol in blood, urine and vitreous humor were lower than 0.20 g/kg in 51.3%, 67.4% and 77.8%, respectively. It was 1.0 g/kg or higher in blood in 4.2% of cases. More EtS negative and PA positive cases were seen in central compared to peripheral blood. Ethanol ratios between urine or vitreous humor and blood were significantly lower in both EtS negative and PA positive cases, but large variations were observed.
CONCLUSION
EtS and PA analysis improve the diagnostic accuracy of ethanol in postmortem cases. Postmortem ethanol formation in vitreous humor and urine were both more frequent than expected and we recommend the analysis of ethanol primarily in peripheral blood if available.
Topics: Autopsy; Body Fluids; Ethanol; Humans; Postmortem Changes; Vitreous Body
PubMed: 34952291
DOI: 10.1016/j.forsciint.2021.111152 -
Clinics (Sao Paulo, Brazil) 2020To evaluate the role of intraocular fluid analysis as a diagnostic aid for uveitis.
OBJECTIVE
To evaluate the role of intraocular fluid analysis as a diagnostic aid for uveitis.
METHODS
Twenty-eight samples (27 patients including 3 HIV-infected patients) with active (n=24) or non-active (n=4) uveitis were submitted to aqueous (AH; n=12) or vitreous humor (VH) analysis (n=16). All samples were analyzed by quantitative PCR for herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Toxoplasma gondii.
RESULTS
The positivity of the PCR in AH was 41.7% (5/12), with 50% (2/4) in immunocompetent and 67% (2/3) in HIV+ patients. The positivity of the PCR in VH was 31.2% (5/16), with 13% (1/8) in immunocompetent and 50% (4/8) in immunosuppressed HIV negative patients. The analysis was a determinant in the diagnostic definition in 58% of HA and 50% of VH.
CONCLUSION
Even in posterior uveitis, initial AH analysis may be helpful. A careful formulation of possible clinical diagnosis seems to increase the chance of intraocular sample analysis being meaningful.
Topics: Aqueous Humor; Cytomegalovirus; DNA, Viral; HIV-1; Herpesvirus 3, Human; Herpesvirus 4, Human; Humans; Immunocompetence; Immunocompromised Host; Polymerase Chain Reaction; Simplexvirus; Toxoplasma; Uveitis; Vitreous Body
PubMed: 31994615
DOI: 10.6061/clinics/2020/e1498 -
Experimental and Clinical Endocrinology... Apr 2020It has been estimated that 15% up to one third of cases of deaths due to diabetic ketoacidosis occur in individuals with so far unknown diabetes. Moreover, cardiac... (Review)
Review
It has been estimated that 15% up to one third of cases of deaths due to diabetic ketoacidosis occur in individuals with so far unknown diabetes. Moreover, cardiac arrhythmias that occur during nocturnal hypoglycaemia include bradycardia and ectopics that may provoke lethal arrhythmias. As postmortem capillary glucose concentrations have no diagnostic value, the postmortem forensic proof of hyperglycaemia or hypoglycaemia remains a challenge. The established but rarely applied method of postmortem determination of glucose and lactate in vitreous humor with or without calculation of the sum formula of Traub could provide reliable exclusion or proof of severe antemortem disorders in glucose metabolism. To date, diagnostic puncture of vitreous humor is more established for the postmortem detection of diabetic ketoacidosis than for the exclusion or proof of lethal hypoglycaemia. Vitreous humor is protected from postmortem degradation and contamination due to its isolated localization. The autolytic process in vitreous humor is considerably delayed compared to blood or liquor. In vitreous humor also the triggering agent of hypoglycaemia (insulin, insulin analogues) is easier to be detected than in blood since insulins are very unstable in postmortem blood. Furthermore, parameters of long term glycaemic control such as 1,5-anhydroglucitol, HbA1c and fructosamine can be determined in vitreous humor. However, limitations and interference factors of this method should be carefully considered. So far, clinical diabetology has taken no broad notice of this useful forensic procedure.
Topics: Diagnosis; Glucose Metabolism Disorders; Humans; Vitreous Body
PubMed: 30340233
DOI: 10.1055/a-0752-0028 -
Clinica Chimica Acta; International... Apr 2021Vitreoretinal lymphoma (VRL) is a subtype of central lymphoma, which at present is hard to diagnose. The gold standard of VRL diagnosis is vitreous cytology, but the...
BACKGROUND
Vitreoretinal lymphoma (VRL) is a subtype of central lymphoma, which at present is hard to diagnose. The gold standard of VRL diagnosis is vitreous cytology, but the vitreous specimen needs to be obtained by the invasive surgery of vitrectomy. Aqueous humor is easier to obtain, has better stability, and has a lower operating risk than vitreous specimens.
METHODS
We studied the diagnostic value of interleukin 10 (IL-10), IL-10/ IL-6 ratio and interleukin score for intraocular lymphoma diagnosis (ISOLD) in both vitreous and aqueous humor for vitreoretinal lymphoma, to determine if aqueous humor could be used to assist in the diagnosis of vitreoretinal lymphoma (VRL) by detecting IL-6 and IL-10.
RESULTS
The area under ROC curve (AUC) of vitreous fluid IL-10, IL-10/IL-6 ratio and ISOLD at the diagnosis of VRL diagnosis were 93.5%, 93.6% and 93.8%, respectively. The AUC of the aqueous humor IL-10, IL-10/IL-6 and ISOLD for VRL diagnosis were 83.8%, 72.8% and 85.9%, respectively.
CONCLUSIONS
Aqueous humor can thus replace vitreous humor as a potential sample type for the diagnosis of intraocular lymphoma.
Topics: Aqueous Humor; Biomarkers, Tumor; Humans; Interleukin-10; Interleukin-6; Lymphoma; Retinal Neoplasms; Vitreous Body
PubMed: 33387464
DOI: 10.1016/j.cca.2020.12.035 -
Journal of Analytical Toxicology May 2016Alternative specimens have been occasionally considered as substitutes for whole blood for postmortem toxicology testing. We studied the applicability of vitreous humor,... (Comparative Study)
Comparative Study
Alternative specimens have been occasionally considered as substitutes for whole blood for postmortem toxicology testing. We studied the applicability of vitreous humor, and evaluated whether it would be suitable to replace (or augment) whole blood for routine drug screening. Results showed that from 51 autopsy cases, we were able to identify an aggregate of 209 findings in whole blood compared with 169 in vitreous. The total number of compounds identified was 71 for whole blood and 60 for vitreous humor. Quantitative analysis showed that whole-blood concentrations of trazodone were several fold higher than vitreous humor concentrations (1.42 ± 0.57 vs. 0.15 ± 0.05 mg/L, respectively) and similar results were also obtained for diazepam (0.37 ± 0.06 vs. 0.13 ± 0.01, respectively). For other drugs such as oxycodone, hydrocodone and doxylamine, a trend suggesting higher concentrations in vitreous humor vs. whole blood was observed; however, this was not significant. Our results are consistent with the limited work of other investigators, and suggest that vitreous humor could be an appropriate matrix for drug screening in postmortem toxicology.
Topics: Antidepressive Agents, Second-Generation; Autopsy; Blood Chemical Analysis; Diazepam; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Humans; Pharmaceutical Preparations; Reproducibility of Results; Substance Abuse Detection; Trazodone; Vitreous Body
PubMed: 26945835
DOI: 10.1093/jat/bkw009 -
Journal of Ocular Pharmacology and... 2018Even though the very thought of an injection into the eye may be frightening, an estimated 6 million intravitreal (IVT) injections were made in the USA during 2016. With... (Review)
Review
Even though the very thought of an injection into the eye may be frightening, an estimated 6 million intravitreal (IVT) injections were made in the USA during 2016. With the introduction of new therapeutic agents, this number is expected to increase. In addition, drug products that are injectable in ocular compartments other than the vitreous humor are expected to enter the back of the eye market in the not so distant future. Besides the IVT route, some of the most actively investigated routes of invasive administration to the eye include periocular, subretinal, and suprachoroidal (SC) routes. While clinical efficacy is the driving force behind new injectable drug product development for the eye, safety is also being improved with time. In the case of IVT injections, the procedural guidelines have evolved over the years to improve patient comfort and reduce injection-related injury and infection. Similar advances are anticipated for other routes of administration of injectable products to the eye. In addition to procedural improvements, the design of needles, particularly those with smaller diameters, length, and controlled bevel angles are expected to improve overall safety and acceptance of injected ophthalmic drug products. A key development in this area is the introduction of microneedles of a length less than a millimeter that can target the SC space. In the future, needles with smaller diameters and lengths, potentially approaching nanodimensions, are expected to revolutionize ophthalmic disease management.
Topics: Administration, Ophthalmic; Animals; Drug Delivery Systems; Humans; Injections, Intraocular; Intravitreal Injections; Needles; Ophthalmic Solutions; Vitreous Body
PubMed: 29206556
DOI: 10.1089/jop.2017.0121 -
Analytical and Bioanalytical Chemistry Jun 2022Ranibizumab is an FDA-approved drug used to treat wet age-related macular degeneration (AMD), diabetic retinopathy, macular edema, and myopic choroidal...
Intact quantitative bioanalytical method development and fit-for-purpose validation of a monoclonal antibody and its related fab fragment in human vitreous and aqueous humor using LC-HRMS.
Ranibizumab is an FDA-approved drug used to treat wet age-related macular degeneration (AMD), diabetic retinopathy, macular edema, and myopic choroidal neovascularization. Bevacizumab is another drug often used off-label to treat wet AMD. In order to reduce unwanted angiogenesis, ranibizumab and bevacizumab target circulating VEGF-A in the eye. Concentration levels in human vitreous and aqueous humor can be used to provide valuable efficacy information. However, vitreous and aqueous humor's aqueous environment, and vitreous humor's viscosity, as well as the stickiness of the analytes can provide bioanalytical challenges. In this manuscript, we describe the development, optimization, and fit-for-purpose validation of an LC-HRMS method designed for intact quantitative bioanalysis of ranibizumab and bevacizumab in human vitreous and aqueous humor following intravitreal administration. In order to fully develop this method, evaluations were conducted to optimize the conditions, including the data processing model (extracted ion chromatograms (XICs) vs deconvolution), carryover mitigation, sample preparation scheme optimization for surrogate and primary matrices, use of internal standard/immunocapture/deglycosylation, and optimization of the extraction and dilution procedure, as well as optimization of the liquid chromatography and mass spectrometry conditions. Once the method was fully optimized, a fit-for-purpose validation was conducted, including matrix parallelism, with a linear calibration range of 10 to 200 µg/mL. The development of this intact quantitative method using LC-HRMS provides a proof-of-concept template for challenging, but valuable new and exciting bioanalytical techniques.
Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Aqueous Humor; Bevacizumab; Humans; Immunoglobulin Fab Fragments; Ranibizumab; Vascular Endothelial Growth Factor A; Vitreous Body
PubMed: 35451621
DOI: 10.1007/s00216-022-04071-x -
Journal of Analytical Toxicology May 2022The interpretation of postmortem γ-hydroxybutyric acid (GHB) concentrations is challenging due to endogenous existence and postmortem GHB production in body tissues and...
Comparative Study: Postmortem Long-Term Stability of Endogenous GHB in Cardiac Blood, Femoral Blood, Vitreous Humor, Cerebrospinal Fluid and Urine with and without Sodium Fluoride Stabilization.
The interpretation of postmortem γ-hydroxybutyric acid (GHB) concentrations is challenging due to endogenous existence and postmortem GHB production in body tissues and fluids. As an additional complication, formation of GHB was also described in stored postmortem samples. We examined cardiac blood, femoral blood, vitreous humor, cerebrospinal fluid and urine of eight different corpses (male/female 5/3, aged 33-92 years, postmortem interval 1-6 days) where no intake of GHB or one of its precursors was assumed. All samples were collected during autopsy and divided into two aliquots. To one of the aliquots, sodium fluoride (NaF, 1% w/v) was added. Both aliquots were vortexed, further divided into seven aliquots and stored at -20°C. GHB concentrations were measured immediately and subsequently 1 day, 7 days, 2 weeks, 4 weeks, 3 months and 6 months, after sample collection using trimethylsilyl derivatization and gas chromatography, coupled to single quadrupole mass spectrometry. Similar progression curves of GHB concentrations were obtained for the different matrices in the individual corpses. Femoral and cardiac blood GHB concentrations were always found to be higher than in vitreous humor, cerebrospinal fluid, and urine irrespective of stabilization and storage time. None of the obtained GHB concentrations exceed the cutoff values for postmortem matrices commonly used for the identification of an exogenous GHB intake (urine, venous blood and cerebrospinal fluid: 30 mg/L, cardiac blood and vitreous humor 50 mg/L). No significant differences were found for the GHB concentrations measured immediately and 6 months after autopsy. However, we found a significant increase for the GHB concentrations 4 weeks as well as 3 months after sample collection, which was followed by a decrease nearly to initial values. There were no significant differences between samples with and without NaF addition. The data presented are useful for the interpretation of GHB concentrations in upcoming death cases, with special attention to storage conditions and different postmortem matrices.
Topics: Autopsy; Cadaver; Female; Gas Chromatography-Mass Spectrometry; Humans; Male; Postmortem Changes; Sodium Fluoride; Sodium Oxybate; Vitreous Body
PubMed: 33893805
DOI: 10.1093/jat/bkab042 -
Survey of Ophthalmology 2020Vitreous floaters are common, related to age, myopia, genetic predisposition, and infiltration of the vitreous body. A subset of patients report symptoms impacting their... (Review)
Review
Vitreous floaters are common, related to age, myopia, genetic predisposition, and infiltration of the vitreous body. A subset of patients report symptoms impacting their quality of vision. Treatment with laser vitreolysis, the use of an Nd:YAG laser to vaporize the collagenous vitreous opacities appears to be used more frequently; however, data regarding long-term safety and effectiveness are lacking. We present currently available data regarding efficacy and safety, as well as additional considerations. Laser vitreolysis of symptomatic floaters should not be routinely performed without additional studies documenting its safety and long-term efficacy. Ideally, the procedure would be effective in most patients and be approved by the Food and Drug Administration based on the results of a Food and Drug Administration registration trial before widespread adoption.
Topics: Eye Diseases; Humans; Laser Therapy; Lasers, Solid-State; Visual Acuity; Vitrectomy; Vitreous Body
PubMed: 32135173
DOI: 10.1016/j.survophthal.2020.02.007