Vitreous Concentrations Research Articles

The impact of vitreomacular traction on vitreous vascular endothelial growth factor and placental growth factor levels in neovascular age-related macular degeneration patients.

To investigate the effect of vitreomacular traction (VMT) on vitreous vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) levels in patients with active neovascular age-related macular degeneration (nAMD). A prospective, interventional, case-control study. The study included a total of 70 patients from whom vitreous samples were obtained. The patients were categorized into four group: 10 patients with active nAMD accompanying VMT, 17 patients with VMT, 24 patients with active nAMD and 19 healthy patients without any diagnosis other than cataract. VEGF and PlGF levels were measured. The mean vitreous VEGF level was 34.7 ± 4.98 pg/ml in the nAMD and VMT group, 32.36 ± 4.55 pg/ml in the VMT group, 34.02 ± 3.79 pg/ml in the nAMD group, and 32.33 ± 2.4 pg/ml in the healthy control group. The mean vitreous PlGF level was 58.92 ± 20.83 pg/ml in the nAMD and VMT group, 46.29 ± 3.45 pg/ml in the VMT group, 54.64 ± 16.88 pg/ml in the nAMD group, and 53.66 ± 19.35 pg/ml in the healthy control group. No significant differences were observed in terms of vitreous VEGF and PlGF concentrations among the groups (p > 0.05 and p > 0.05, respectively). Aqueous humour VEGF and PlGF levels were significantly higher than vitreous levels in nAMD patients (p = 0.005 and p = 0.005, respectively). The present study found no increases in vitreous VEGF and PlGF levels in both VMT + nAMD and VMT cases. Furthermore, patients with nAMD had significantly higher levels of PlGF and VEGF in aqueous humour compared to vitreous levels.

Pharmacokinetic/pharmacodynamic analysis of geographic atrophy lesion area in patients receiving pegcetacoplan treatment or sham.

Pegcetacoplan is a complement C3/C3b inhibitor indicated for the treatment of geographic atrophy (GA). A population pharmacokinetic (PK)/pharmacodynamic (PD) analysis of pegcetacoplan used GA lesion area measurements from three clinical studies to determine the effect of pegcetacoplan exposure on GA progression. A base disease progression model was developed using data from sham-treated eyes and untreated fellow eyes, followed by treatment effect assessment in dose-response and PK/PD models. In total, 1501 patients from FILLY (NCT02503332), OAKS (NCT03525613), and DERBY (NCT03525600) received intravitreal pegcetacoplan 15 mg monthly or every other month (EOM) or sham treatment monthly or EOM and were included in the population analysis of lesion area. Disease progression over time was adequately described as linear-with-time over the 24-month maximal study duration. Disease-specific covariates associated with slower lesion growth were unilateral, unifocal, and subfoveal GA lesions and >20 intermediate or large drusen groups (≥63 μm) at baseline. The dose-response model estimated 0.80-fold (95% CI: 0.75, 0.84) and 0.83-fold (95% CI: 0.78, 0.87) reductions in GA lesion growth rate with pegcetacoplan monthly and EOM, respectively, versus sham. A relationship between vitreous humor concentration and GA lesion growth rate was quantified as 2.6% per unit of log-transformed vitreous pegcetacoplan concentration in the PK/PD model. PK/PD predictions of treatment effect based on exposure (pegcetacoplan monthly: 0.80 [90% CI: 0.77, 0.84]; pegcetacoplan EOM: 0.83 [90% CI: 0.80, 0.86]) were consistent with predictions based on dose response. These results support the benefit of pegcetacoplan administered monthly or EOM in slowing GA lesion growth.

Simultaneous determination of four ethanol biomarkers in blood: avalidated method for use in forensic toxicology in 257 postmortem samples

Purpose: Ethyl alcohol is the most widely and legally available intoxicating substance. However, excessive consumption is associated with numerous negative social consequences, including the potential for significant health risks. Rapid and simple diagnosis of alcohol use is necessary to initiate appropriate and effective treatment and is critical in forensic toxicological analysis. Ethanol biomarkers have clinical utility in the detection, diagnosis, and treatment of alcohol use disorders. Materials and Methods: An analytical method for the simultaneous determination of four different alcohol biomarkers ethyl glucuronide (EtG), ethyl sulphate (EtS), N-acetyltaurine (NAcT), and 16:0/18:1-phosphatidyl ethanol (PEth) in blood samples from forensic cases was developed, validated and verified for the accurate monitoring of alcohol abuse and dependence. Analyses were performed using a liquid chromatography-mass spectrometry system. Results: 257 blood and vitreous samples were collected from 255 male and 2 female subjects aged 16-80 years (average 44±14.82) from the Forensic Medicine Council of Turkey and analyzed for ethanol biomarkers and calculated ethanol concentrations. A total of 257 blood samples were found to contain ethanol, with concentrations ranging from 12.0 to 444.0 mg/dL. Vitreous concentrations ranged from 23 mg/dL to 597 mg/dL. The limit of detection (LOD) for EtG, EtS, NAcT, and PEth were 3.1, 3.9, 7.3, and 5.7 ng/mL respectively in blood samples. The limit of quantification (LOQ) for EtG, EtS, NAcT, and PEth were 7.8, 8.4, 18.3, and 13.1 ng/mL, respectively in blood samples. Conclusion: The method has potential in forensic toxicology as an invaluable tool for the accurate and simultaneous identification of biomarkers of alcohol use and dependence in different biological samples.

TNFα and IL-8 vitreous concentrations variations with two antidiabetic therapies in patients with proliferative diabetic retinopathy: an observational study

BackgroundAntidiabetic therapies are effective, but could indirectly modify the inflammatory response in the ocular microenvironment; therefore, a study was developed to evaluate the inflammatory cytokine profile in the vitreous humor of diabetic patients with retinopathy under treatment with antidiabetic drugs.MethodsObservational, comparative, retrospective, cross-sectional study. Interleukins 1β, 6, 8, 10, and tumor necrosis factor-alpha (TNFα) were evaluated in the vitreous humor obtained from patients with type 2 diabetes mellitus, proliferative diabetic retinopathy, and concomitant retinal detachment or vitreous hemorrhage, and who were already on antidiabetic treatment with insulin or metformin + glibenclamide. The quantification analysis of each cytokine was performed by the cytometric bead array (CBA) technique; medians and interquartile ranges were obtained, and the results were compared between groups using the Mann-Whitney U test, where a p-value < 0.05 was considered significant.ResultsThirty-eight samples; quantification of TNFα concentrations was higher in the group of patients administered insulin, while interleukin-8 was lower; in the metformin + glibenclamide combination therapy group, it occurred inversely. In the stratified analysis, the highest concentrations of interleukin-8 and TNFα occurred in patients with vitreous hemorrhage; however, the only statistical difference existed in patients with retinal detachment, whose TNFα concentration in the combined therapy group was the lowest value found (53.50 (33.03–86.66), p = 0.03). Interleukins 1β, 6, and 10 were not detected.ConclusionInterleukin-8 and TNFα concentrations are opposite between treatment groups; this change is more accentuated in patients with proliferative diabetic retinopathy and vitreous hemorrhage, where the highest concentrations of both cytokines are found, although only TNFα have statistical difference.

Ethanol concentrations in various biological specimens: Living and postmortem forensic toxicology analysis and comprehensive literature review

Alcohol use upsurges the risk for many chronic ill-health consequences such as hepatitis, malignancies, and disastrous outcomes like road traffic accidents ending in fatal injuries. Biochemical and toxicological analysis of different body fluids is crucial for identifying the cause of death and postmortem interval in many forensic cases. Blood, urine, and vitreous fluid are the most valuable body fluids for detecting alcohol during any toxicological analysis. Alcohol is responsible for widespread morbidity and mortality worldwide. Blood alcohol concentration (BAC) is a necessary toxicological test to investigate various crime and accident scenes. This study comprehensively explores the demographic characteristics, BAC distribution, and correlations of alcohol concentrations in postmortem and living cases. Postmortem cases (N = 166) reveal intriguing demographic patterns, with notable variations in year distribution, nationality, sex, age groups, occupation, smoking habits, place of death, and psychiatric history. Living cases (N = 483) exhibit distinct demographic profiles, emphasizing differences in year distribution, nationality, sex, age groups, and smoking habits.Analysis of BAC distribution reveals diverse patterns in both postmortem and living cases, providing valuable insights into the prevalence of different BAC levels in each group. Correlation analyses unveil strong associations between alcohol concentrations in various biological samples in postmortem cases, highlighting the interdependence of blood, vitreous, and urine alcohol concentrations. Conversely, living cases display a moderate positive correlation between blood and urine alcohol concentrations.Comparative analyses showcase significant differences in mean alcohol concentrations between postmortem and living cases, suggesting variations in alcohol metabolism and distribution. These findings underscore the importance of considering temporal factors in interpreting alcohol concentrations in forensic and clinical contexts.In conclusion, this study enhances our understanding of alcohol-related incidents by delineating demographic profiles, BAC distributions, and correlations between different biological samples. Such insights are crucial for refining investigative and clinical approaches, contributing to the broader fields of forensic science and public health.

Comparative Ocular Pharmacokinetics of Dexamethasone Implants in Rabbits.

Purpose: Dexamethasone eye implant has been used to treat macular edema and non-infectious uveitis. To date, its ocular pharmacokinetics are not fully characterized, and the development of generic preparations is in progress, as the patent of the original brand expires soon. Therefore, this work was designed to 1) determine the time course of vitreous dexamethasone concentrations following intravitreal implantation in rabbits and 2) explore the alternative use of NDF-SI01 from a pharmacokinetic point of view compared to Ozurdex®, which is currentlyused in the market. Methods: Ozurdex® and NDF-SI01 were implanted into the right and left eyes of the rabbit, respectively. A serial vitreous collection was performed to minimize the sacrifice of animals, and dexamethasone concentrations were measured by HP LC-MS/MS. Results: After implantation, dexamethasone concentration reaches the maximum concentration (3.1 μg/mL) in 19.5 days and decreases with a half-life of 40.3 h. AUC and clearance are 683.9 μg·h/mL and 1.29 mL/h, respectively. There is no significant difference in pharmacokinetic parameters between NDF-SI01 and Ozurdex®. The overall patterns of the cumulative release of both implants are similar. Conclusions: NDF-SI01 could alternate Ozurdex® in clinics based on the in vivo comparative pharmacokinetic study and in vitro dissolution test.

CLINICAL CHARACTERIZATION OF AQUEOUS AND VITREOUS RETINOL-BINDING PROTEIN 3 CONCENTRATIONS IN RELATION TO DIABETIC RETINOPATHY SEVERITY, RETINAL STRUCTURES, AND SYSTEMIC COMPLICATIONS.

To evaluate Retinol-Binding Protein 3 (RBP3) from photoreceptors in aqueous and its association with vitreous concentrations, diabetic retinopathy (DR) severity, retinal layer thickness, and clinical characteristics in people with diabetes. RBP3 concentration was measured by custom-developed enzyme-linked immunosorbent assay in aqueous and correlated with vitreous concentrations in patients from the 50-Year Medalist study and Beetham Eye Institute at Joslin Diabetes Center. Aqueous RBP3 concentration (N = 131) was elevated in eyes with no to mild DR (mean ± SD 0.7 nM ± 0.2) and decreased in eyes with moderate to severe DR (0.65 nM ± 0.3) and proliferative DR (0.5 nM ± 0.2, P < 0.001) compared to eyes without diabetes. Aqueous and vitreous RBP3 concentrations correlated with each other (r = 0.34, P = 0.001) and between fellow eyes (P < 0.0001). History of retinal surgery did not affect aqueous RBP3 concentrations, but cataract surgery affected both vitreous and aqueous levels. Elevated aqueous RBP3 concentration associated with increased thickness of the outer nuclear layer (P = 0.004) and correlated with hemoglobin A1c, whereas vitreous RBP3 concentrations correlated with diabetic systemic complications. These findings suggest that aqueous RBP3 concentration may be an important endogenous clinical retinal protective factor, a biomarker for DR severity, and a promising VEGF-independent clinical intervention target in DR.

The Association of Intraocular Efavirenz Concentrations and HIV-1 Viral Load Among Persons With HIV.

Efavirenz (EFV) is commonly used in combination antiretroviral therapy. However, in our previous study, many persons living with HIV exhibited ocular complications despite undergoing effective combination antiretroviral therapy. Here, we aimed to determine the intraocular EFV concentrations in the vitreous and analyze the factors affecting viral load in the vitreous in patients with HIV-associated retinopathies. Observational, retrospective study. Fourteen patients receiving EFV in combination with an antiretroviral therapy who underwent pars plana vitrectomy were enrolled between January 2019 and August 2022. The patients were divided into 2 groups based on presence or absence of retinal detachment (RD). Patient characteristics and HIV-1 RNA levels in plasma and vitreous were recorded during pars plana vitrectomy. Paired blood plasma and vitreous samples were obtained for EFV concentration analysis using ultra-high-performance liquid chromatography/tandem mass spectrometry. The median age of the enrolled patients was 48 years (interquartile range, 32.25-53.25), including 12 men and 2 women. Median vitreous and plasma EFV concentrations were 141.5 (interquartile range, 69.63-323.75) and 2620 ng/mL (1680-4207.5), respectively. Median ratio of vitreous/plasma EFV concentrations in the paired samples among all participants was 0.053 (0.018-0.118). Median vitreous/plasma EFV concentrations significantly differed between the non-RD and RD groups (0.04 vs 0.12, P = 0.042). The vitreous EFV concentrations were insufficient to inhibit viral replication in intraocular tissues, which may be because of poor penetration of the blood-retinal barrier. High vitreous EFV concentrations were associated with RD, indicating a correlation between the EFV concentration and the severity of blood-retinal barrier disruption. It implied that EFV was not a suitable antiviral drug to inhibit HIV-1 replication in ocular tissues.

Polymeric Propranolol Nanoparticles for Intraocular Delivery: Formulation, Characterization, and Vitreous Pharmacokinetics.

Recent studies have reported the promising effect of intravitreal propranolol on retinal neovascularization. However, rapid clearance and short half-life of the drug in the vitreous are the main drawbacks of this therapeutic approach. This study investigates the extension of the residence time of propranolol in the vitreous by polymeric nanoparticles (NPs) with the prospect of improving choroidal neovascularization treatment. The poly (lactic-co-glycolic) acid (PLGA) NPs were fabricated by a modified double emulsion solvent evaporation method and the obtained NPs were characterized for their size, poly dispersity index (PDI), and surface image. The in vitro release, cell cytotoxicity, and uptake of NPs were also evaluated. To investigate the effect of the vitreous pharmacokinetic drug loaded NPs versus that of the free propranolol, they were intravitreally injected into the rabbits' eyes and the drug vitreous concentrations in defined intervals were analyzed by high performance liquid chromatography (HPLC). The spherical NPs with about 230 nm size, and almost 10% drug loading were obtained. Based on the 3-(4, 5-Dimethylthiazol-2-Yl)-2, 5-Diphenyltetrazolium Bromide (MTT) outcomes, 30 µg/ml of propranolol was considered as the guide dosage in the intravitreal injection. Confocal microscopy images verified the presence of labeled NPs in the posterior segment after five days of receiving the injection. In vivo assay revealed that the vanishing rate of propranolol in rabbits treated with propranolol NPs was reduced at twice the rate as compared to that of the vanishing rate experienced with only the free drug. PLGA NPs can prolong the existence of propranolol in both vitreous and posterior ocular tissues, and thus, may provide an effective approach in treatment of posterior segment neovascularization.

Serum and Vitreous Levels of Placenta Growth Factor in Diabetic Retinopathy Patients: Correlation With Disease Severity and Optical Coherence Tomographic Parameters.

Purpose The primary objective of this study was to compare placenta growth factor (PlGF) levels in the serum and vitreous of diabetic retinopathy (DR) patients to non-diabetic controls. Additionally, the study aimed to establish associations between serum and vitreous PlGF concentrations and to examine the correlation between vitreous PlGF in DR patients and morphological parameters. Methods This study included serum and vitreous samples from 38 patients, including 21 patients with DR and 17 non-diabetic controls. The control group included non-diabetic patients with rhegmatogenous retinal detachment with retinal tears secondary to posterior vitreous detachment or trauma. PlGF levels were quantified in vitreous and serum samples using an enzyme-linked immunosorbent assay (ELISA). Optical coherence tomography (OCT) scans from DR patients were evaluated to measure the central retinal thickness (CRT) and macular volume (MV). Results DR patients had significantly higher mean vitreous PlGF levels compared to non-DR patients (70.0±39.2 vs. 46.47±9.7 pg/mL, p-value=0.004). However, no significant increase in mean serum PlGF levels was observed in DR patients (p-value=0.232). Within the DR group, proliferative DR (PDR) patients presented significantly higher vitreous PlGF levels than non-PDR (NPDR) patients (76.5±41.0 vs. 42.5±5.0 pg/mL, p-value=0.009). There was no association between serum and vitreous PlGF levels. The correlation between vitreous PlGF levels and morphological parameters was rsp=0.175, p-value=0.488 for CRT, and rsp=0.288, p-value=0.262 for MV. Conclusion This study emphasizes the important role of PlGF in neovascularization, specifically highlighting its overexpression exclusively in vitreous from PDR patients. The observed increase in PlGF levels may be indicative of disease severity. The lack of correlation between vitreous and serum PlGF levels suggests a potential dissociation between intravitreal and systemic PlGF synthesis. Consequently, targeting PlGF in therapeutic approaches may offer an additional strategy for ocular pathologies with a neovascular component.

Estimation of Time Since Death by Potassium ion Level in the Vitreous Fluids: A Postmoterm Study in a Tertiary Care Center, South India

Background: It is of great value to find time since death in the medicolegal investigations like serious crimes.Vitreous humor was more often used for the biochemical analysis as it is less contaminated or not affected by the putrefactive changes than other fluids of the body. It was stated by many researchers that potassium levels in the vitreous humour is more accurate in predicting time since death.Aim: The aim of the study is to assess the time since death using potassium level in the vitreous humorMethodology: This study includes 54 cases of victims brought to the tertiary care hospital based on inclusion and exclusion criteria. Cases with known time of death and with clear vitreous humor samples were included. Baseline characteristics like name, age, gender, exact time since death was collected. Vitreoushumor was collected through appropriate standardized technique. Sampling time was also noted. The collected data was entered in MS excel and analysis done in SPSS 23 software. P value &lt;0.05 is considered to be significant.Results: Majority of the study participants belongs to 57-67 years of age group (28%) followed by 27-37 years of age (22%).Male predominance was observed in our study 41(76%). There is a linear correlation found between the vitreous potassium concentration and the postmortem interval (R2=0.907). The rate of the vitreous potassium increase was 0.36 meq/hr (Coefficient of regression =2.76 meq/l/hr)Conclusion: There is a linear relationship found between vitreous potassium concentration and time since death.Thus potassium in the vitreous can be used for assessing the time since death.

The interest of using vitreous humor for γ-hydroxybutyrate (GHB) quantification in related fatalities: Stability evaluation, case report and literature review

Analysis and interpretation of the findings for γ-hydroxybutyrate (GHB) in related fatalities remains problematic. Indeed, GHB is a naturally occurring compound present in both the mammalian central nervous system and peripheral tissue. Moreover, a postmortem increase in endogenous GHB concentration has been observed, especially in blood. Facing this issue, the use of an alternative matrix such as vitreous humor (VH) can thus be particularly interesting for GHB testing and quantification. VH is considered to be less prone to postmortem redistribution, is easy to collect, and has relatively few interfering compounds for the analytical process. In this context, the authors report the case of a GHB-related fatality involving 22-year-old male. In this case, GHB femoral blood (FB) (790 mg/L) and vitreous (750 mg/L) concentrations appeared similar with a FB to VH (FB/VH) ratio of 1.05. In addition, other similar cases with both GHB blood and vitreous concentrations were reviewed. Five cases were identified. The blood to VH ratios ranging from 0.13 to 2.58. Finally, GHB stability was documented in postmortem blood and VH, in order to address the reliability of VH as an alternative matrix for GHB quantitation at postmortem. GHB appeared relatively stable in postmortem blood specimens (at 50 mg/L) over a period of 28 days when stored at +4 °C or −20 °C. The same results were observed in VH specimens.

Vitreous Humor Proteomic Profile in Patients With Vitreoretinal Lymphoma.

Vitreoretinal lymphoma is a high-grade malignant non-Hodgkin lymphoma with poor prognosis. The objective of this study was to elucidate the proteome profile of the vitreous in patients with vitreoretinal lymphoma (VRL), aiming to advance understanding of the pathophysiology of VRL. Comprehensive proteomic analyses of vitreous humor using liquid chromatography with tandem mass spectrometry were performed for 10 patients with VRL, 10 control patients with idiopathic epiretinal membrane or macular hole, and 10 patients with ocular sarcoidosis. Differentially expressed proteins (DEPs) were identified by comparing VRL with controls and sarcoidosis, and functional pathway analysis was performed. Finally, vitreous concentrations of representative DEPs that were significantly upregulated in proteomics study were measured by ELISA using a separate cohort. In total, 1594 proteins were identified in the vitreous humor of VRL, control, and sarcoidosis samples. Also, 282 DEPs were detected in VRL, 249 upregulated and 33 downregulated, compared with controls. Enrichment pathway analysis showed alterations in proteasome-related pathways. Compared to controls and sarcoidosis, 14 DEPs in VRL showed significant upregulation. In the validation study, ELISA confirmed significantly higher vitreous concentrations of PSAT1, YWHAG, and 20S/26S proteasome complex in VRL compared with controls and sarcoidosis. Among the upregulated DEPs, vitreous PITHD1 and NCSTN concentrations correlated positively with vitreous IL-10 concentrations. This study highlights aberrations in protein expression pattern in the vitreous of patients with VRL. The DEPs identified in this study may play pivotal roles in VRL pathogenesis, providing insights to enhance understanding of VRL pathophysiology and contribute to the development of VRL biomarkers.

Evaluating the long-term biological stability of cytokine biomarkers in ocular fluid samples

PurposeThe quality of biological fluid samples is vital for optimal preanalytical procedures and a requirement for effective translational biomarker research. This study aims to determine the effects of storage duration...

Role of postmortem toxicology in drowning investigations

AbstractDrowning is the third most common cause of unintentional injury death worldwide. In forensic medicine, drowning refers to an event in which the victim dies due to liquid penetrating into the airways or due to submersion in a liquid. Medico‐legal examination of bodies found in water is a challenging task. Establishing proper cause and manner of death requires the joint efforts of the police, medical examiner, and representatives of postmortem toxicology. Information of the circumstances, the victim's individual characteristics and medical background, together with postmortem findings is required. The presence of alcohol and drugs revealed by postmortem toxicology can give insight into the decedent's medical history, drug abuse history, and possible impairment at the time of death. There is ample epidemiological research indicating that alcohol is the most important single contributing factor for fatal drowning, while hypno‐sedative medicines and illicit drugs, especially amphetamines, also appear to pose a risk. Evidence shows that alcohol can be produced postmortem in a submerged body by microbial contamination and fermentation, and this phenomenon is even more significant the higher the water temperature and the longer the submersion time. The reliability of the blood alcohol concentration obtained can be verified in many ways, for example by comparing the ratios of blood, vitreous and urine alcohol concentrations with reference values, or by testing for non‐oxidative ethanol metabolites, the presence of which suggests antemortem alcohol ingestion. Compared to alcohol postmortem changes, very little is known about the long‐term stability of drugs in bodies found in water.This article is categorized under: Toxicology &gt; Analytical Toxicology &gt; Post‐Mortem

Vitreous Levels of Vascular Endothelial Growth Factor and Platelet-Derived Growth Factor in Patients with Proliferative Diabetic Retinopathy: A Clinical Correlation.

Background: The global epidemic status of diabetic retinopathy (DR) and its burden presents an ongoing challenge to health-care systems. It is of great interest to investigate potential prognostic biomarkers of DR. Such markers could aid in detecting early stages of DR, predicting DR progression and its response to therapeutics. Herein, we investigate the prognostic value of intravitreal concentrations of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) in a DR cohort. Materials and methods: Vitreous sample acquisition was conducted at King Abdullah University Hospital (KAUH) between December 2020 and June 2022. Samples were obtained from any patient scheduled to undergo a pars plana vitrectomy (PPV) for any indication. Included patients were categorized into a DR group or a corresponding non-diabetic (ND) control group. Demographics, clinicopathological variables, standardized laboratory tests results, and optical coherence tomography (OCT) data were obtained for each included individual. Intravitreal concentrations of VEGF and PDGF were assessed using commercial enzyme-linked immunosorbent assay (ELISA). Results: A total of 80 eyes from 80 patients (DR group: n = 42 and ND control group: n = 38) were included in the analysis. The vitreous VEGF levels were significantly higher in the DR group compared to the ND control group (DR group 5744.06 ± 761.5 pg/mL versus ND control group 817.94 ± 403.1 pg/mL, p = 0.0001). In addition, the vitreous PDGF levels were also significantly higher in the DR group than those in the ND control group (DR group 4031.51 ± 410.2 pg/mL versus ND control group 2691.46 ± 821.0 pg/mL, p = 0.001). Bassline differences between test groups and clinical factors impacting VEGF and PDGF concentrations were investigated as well. Multiple regression analysis indicated PDGF as the sole independent risk factor affecting best-corrected visual acuity (BCVA) at the last follow-up visit: the higher the PDGF vitreous levels, the worst the BCVA. Conclusions: Vitreous concentrations of VEGF and PDGF are correlated with DR severity and may exhibit a possible prognostic potential value in DR. Further clinical and experimental data are warranted to confirm the observed findings and to help incorporate them into daily practice.

Utility of Ocular β-D-Glucan Testing in Patients with Fungal Endophthalmitis.

To assess the diagnostic utility of (1→3)-β-D-glucan (BDG) in ocular fluid of patients with fungal endophthalmitis. This prospective pilot single-center study evaluated aqueous and vitreous humor BDG levels of suspected fungal endophthalmitis, bacterial endophthalmitis, and noninfectious controls with the standard Fungitell assay and the Fungitell STAT assay. BDG levels were compared using generalized linear models followed by post-hoc pairwise comparisons. Seven fungal endophthalmitis, six bacterial endophthalmitis, and 17 non-infectious ocular samples were evaluated. Mean aqueous BDG concentrations were 204, 11.0, and 9.6 pg/ml for fungal endophthalmitis, bacterial endophthalmitis and non-infectious controls, respectively (p=0.01, fungal vs. bacterial; p=0.0005, fungal vs. non-infectious controls). Mean vitreous BDG concentrations were 165, 30.3, and 5.4 pg/ml, respectively (p=0.001 for fungal vs. bacterial; p<0.0001 for fungal vs. non-infectious controls). Mean vitreous BDG index (Fungitell STAT) values were 1.7, 0.4, and 0.3, respectively (p=0.001, fungal vs. bacterial; p=0.0004, fungal vs. non-infectious controls). The Pearson correlation between BDG levels and BDG index was high (correlation coefficient=0.99, p<0.001). Significantly elevated ocular BDG levels were found in fungal endophthalmitis compared to bacterial endophthalmitis and non-infectious controls. Our study suggests a potential utility for BDG testing in the diagnosis of fungal endophthalmitis, and a larger study is warranted.

Does vitreous galactin-3, copeptin and retina binding protein-4 concentrations change in diabetic retinopathy?

Aims: This study aimed to investigate whether the concentrations of Galactin-3 (G-3), Copeptin (CP) and Retina Binding Protein-4 (RBP-4) are affected in the vitreous humor of patients with diabetic retinopathy (DR).&#x0D; Methods: Thirty-six patients with diabetes mellitus (DM) were included in the study, consisting of 10 patients without DR and 26 patients with proliferative diabetic retinopathy (PDR). The control group comprised 15 patients who underwent vitrectomy for epiretinal membrane and macular hole surgeries. Vitreous CP, G-3, and RBP-4 concentrations were examined using the enzyme-linked immunosorbent assay (ELISA) method. The groups were compared internally&#x0D; Results: We did not observe any significant differences in the concentrations of G-3, CP and RBP-4 in the vitreous humor between diabetic patients and the control group (p=0.56, p=0.65 and p=0.11, respectively). When comparing vitreous samples of diabetic subgroups with and without DR findings to the control group, no significant differences were detected (p=0.51, p=0.66, and p=0.19, respectively).&#x0D; Conclusion: Our results indicate that the concentrations of G-3, CP, and RBP-4 in the vitreous humor remain unchanged in both diabetic patients and those with proliferative diabetic retinopathy (DRP).

In vivo measurement of T1 in the vitreous humor of patients with ischemic retinal disease.

To demonstrate MR T1 mapping in vivo as a method to non-invasively estimate vitreous oxygen concentration in ischemic eye disease. Patients with ischemic eye disease (central retinal vein occlusion, ocular ischemic syndrome, and proliferative diabetic retinopathy) were prospectively recruited. MRI was performed on each patient before any treatment, with T1 mapping acquired using an inversion recovery TrueFISP sequence at several inversion times, from a single slice positioned through the center of both eyes in the axial oblique plane. A phantom study measuring seven different concentrations of vitronectin, a protein released in ischemic eye disease, was undertaken to determine its potential confounding effect on T1 . Ten participants were recruited (eight central retinal vein occlusion, one ocular ischemic syndrome, and one proliferative diabetic retinopathy). Of the eight central retinal vein occlusion cases, there was a statistically different vitreous T1 in the diseased eye compared to the healthy control eye (4.306 vs. 4.518 s, p = 0.008). T1 times did not significantly alter across the range of vitronectin concentrations. Ischemic eye disease decreases vitreous T1 , potentially implying an increase in vitreous partial pressure of oxygen (pO2 ) concentration given what is known from the relationship between 1/T1 and pO2 . Potential theories for this unexpected result are discussed. This study provides further data on this technique, with potential clinical application in eye disease.

Population Pharmacokinetics of Ranibizumab Delivered via the Port Delivery System Implanted in the Eye in Patients with Neovascular Age-Related Macular Degeneration.

The port delivery system with ranibizumab (PDS) is designed to continuously deliver ranibizumab to maintain therapeutic drug concentrations in the vitreous of the eye for an extended duration. The PDS has been evaluated for the treatment of neovascular age-related macular degeneration in the Ladder (PDS 10, 40, and 100mg/mL, with refill exchanges as needed, versus monthly intravitreal ranibizumab 0.5mg), Archway (PDS 100mg/mL with 24-week refill exchanges, versus monthly intravitreal ranibizumab 0.5mg), and ongoing Portal (PDS 100mg/mL with 24-week refill exchanges) clinical trials. Data from Ladder, Archway, and Portal were used to develop a population pharmacokinetics (PK) model to estimate the ranibizumab release rate from the PDS implant, describe ranibizumab PK in serum and aqueous humor, and predict the concentration in vitreous humor. A model was developed to adequately describe the serum and aqueous humor PK data, as suggested by goodness-of-fit plots as well as visual predictive checks. In the final model, the first-order implant release rate was estimated to be 0.00654 (1/day), corresponding to a half-life of 106days, consistent with the implant release rate determined invitro. The model-predicted vitreous concentrations achieved with PDS 100mg/mL given every 24weeks were below the intravitreal peak concentration and above the intravitreal trough concentration of ranibizumab over the entire 24-week refill interval. The results demonstrate a durable release of ranibizumab from the PDS with a half-life of 106days, providing vitreous exposure to ranibizumab for at least 24weeks that is within the range of exposure for monthly intravitreal treatment.