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BMC Ophthalmology Dec 2022Quantitative analysis of vitreous inflammatory and angiogenic factors from patients with proliferative diabetic retinopathy (PDR) or diabetic macular edema (DME).
PURPOSE
Quantitative analysis of vitreous inflammatory and angiogenic factors from patients with proliferative diabetic retinopathy (PDR) or diabetic macular edema (DME).
MATERIALS AND METHODS
Collection of undiluted vitreous samples from 20 diabetic patients: 13 with proliferative diabetic retinopathy (PDR) and 7 with diabetic macular edema (DME). DME patients had suboptimal response to anti-VEGF treatment. Samples from 11 control patients, with vitreomacular interface pathology such as idiopathic epiretinal membrane (iERM) (n = 4), vitreomacular traction syndrome (VMT) (n = 3) and full thickness macular hole (FTMH) (n = 3), were also collected. The levels of IL1b, IL6, IL8, IL27, TNFα, ICAM-1, VCAM, MCP-1, VEGFA and LCN2 were measured using cytometry flow analysis. Median values were compared with Mann-Whitney test since the distributions were skewed. Statistical analysis was performed with the Statistical Package for Social Sciences software (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.).
RESULTS
The median concentration of LCN2, IL6, IL8, IL1b, IL27, ICAM, VCAM-1, MCP-1, TNFa and VEGFA was higher in PDR patients than in controls. Similarly, the median concentration of LCN2, IL6, IL8, IL27, ICAM, VCAM-1, TNFa and VEGFA was higher in DME patients than in controls. In particular, median LCN2 concentration in diabetic patients was 5,711 pg/ml (interquartile range [IR] = 2,534), while in controls was 2,586 pg/ml (IR = 2,345). Moreover, median LCN2 was 6,534 pg/ml in the DME group (IR = 6,850) and 4,785 pg/ml in the PDR group (IR = 2,608), (p = 0.025).
CONCLUSION
Various inflammatory and angiogenic factors are involved in the pathophysiology of PDR and DME. Elevated vitreous levels of LCN2 in PDR and especially in DME patients reveal a potential pathogenic association. More extended studies could verify LCN2 as an alternative therapeutic target.
Topics: Humans; Angiogenesis Inducing Agents; Diabetes Mellitus; Diabetic Retinopathy; Interleukin-27; Interleukin-6; Interleukin-8; Macular Edema; Vascular Cell Adhesion Molecule-1; Vitreous Body; Lipocalin-2
PubMed: 36536319
DOI: 10.1186/s12886-022-02733-z -
International Journal of Ophthalmology 2023To detect the concentrations of reactive oxygen species (ROS), transient receptor potential mucin-1 (TRPML1), and autophagy-related (Atg) proteins (LC3-I, LC3-II, and...
AIM
To detect the concentrations of reactive oxygen species (ROS), transient receptor potential mucin-1 (TRPML1), and autophagy-related (Atg) proteins (LC3-I, LC3-II, and Beclin1) in vitreous humor of patients with simple rhegmatogenous retinal detachment (RRD).
METHODS
RRD patients enrolled as the RRD group, and patients with idiopathic macular hole (IMH) and idiopathic macular epiretinal membrane (IMEM) were enrolled as control group. The levels of ROS, TRPML1, LC3-I, LC3-II, and Beclin1 in vitreous humor of patients in the RRD and control groups were detected by enzyme-linked immunosorbent assay (ELISA).
RESULTS
The RRD group included 28 eyes 28 patients and had a higher concentration of ROS in vitreous humor (631.86±18.05 vs 436.34±108.22 IU/mL, <0.05). The ROS level in patients with a wide retinal detachment (RD) extent (RD range ≥1/2) was higher than that with a narrow RD extent (RD range<1/2, <0.05). ROS concentration was negatively correlated with RD time (=-0.46, =0.01). The expression levels of LC3-I and Beclin1 significantly decreased in RRD (<0.05), but there were no correlations with the RD time, RD extent, or macular involvement.
CONCLUSION
In eyes with RRD, the concentration of ROS in vitreous humor increases and the expression levels of Atg proteins decrease, reflecting possibly that autophagy is inhibited.
PubMed: 36935782
DOI: 10.18240/ijo.2023.03.03 -
Ophthalmic Research 2022The aim of this study was to compare the flow dynamics of the dual-blade to the single-blade beveled-tip vitreous cutters.
INTRODUCTION
The aim of this study was to compare the flow dynamics of the dual-blade to the single-blade beveled-tip vitreous cutters.
METHODS
The aspiration rates of balanced salt solution (BSS) and swine vitreous were measured for the 25-gauge and 27-gauge dual- and single-blade beveled-tip vitreous cutters. The flow dynamics of BSS and diluted vitreous mixed with fluorescent polymer at the maximal cutting rates and the reflux of BSS were measured in images obtained by a high-speed camera. The distal end of the cutter was defined as the head end.
RESULTS
The aspiration rates of BSS and vitreous by the 25- and 27-gauge dual-blade cutters were significantly higher than those of both single-blade cutters at the maximal cutting rate (all p ≤ 0.01). The mean aspiration flow of BSS in front of the port from a lateral view was significantly faster for both dual-blade cutters than for both single-blade cutters (p = 0.003, p = 0.019). The angle of the mean flow of BSS of both dual-blade cutters was from the distal end (p < 0.001, p < 0.001) but that of the single-blade cutters was from the proximal end. The velocity and angle of the mean reflux flow of both types of cutters were not significantly different. The mean aspiration flow of diluted vitreous was significantly faster for 25-gauge dual-blade cutters with the angle more from the proximal end and 27-gauge dual-blade cutters more from the distal end than both single-blade cutters (p = 0.018, p = 0.048).
CONCLUSION
The dual-blade beveled-tip vitreous cutters improve the efficiency of the vitrectomy procedures and maintain the distal aspirating flow by the beveled tip.
Topics: Animals; Microsurgery; Swine; Vitrectomy; Vitreous Body
PubMed: 34942621
DOI: 10.1159/000521468 -
Ophthalmology. Retina Oct 2020To evaluate the association between retinopathy of prematurity (ROP) and vitreous findings in premature infants detected by handheld spectral-domain (SD) OCT. (Observational Study)
Observational Study
PURPOSE
To evaluate the association between retinopathy of prematurity (ROP) and vitreous findings in premature infants detected by handheld spectral-domain (SD) OCT.
DESIGN
Prospective, observational cohort study.
PARTICIPANTS
Consecutive sample of 92 premature infants requiring ROP screening at 2 academic neonatal intensive care units between July 2015 and March 2018.
METHODS
Infants underwent handheld SD OCT at the time of routine ROP examinations. Two masked, trained graders analyzed right-eye vitreoretinal findings, including semiautomated quantification of punctate hyperreflective vitreous opacities within 5 foveal or parafoveal B-scans (vitreous opacity ratio).
MAIN OUTCOME MEASURES
Excluding posttreatment data, vitreous findings were compared with clinical ROP diagnoses.
RESULTS
Agreement between image graders for all vitreoretinal findings was 91% (κ = 0.86; 95% confidence interval, 0.82-0.90; P < 0.001). Among 92 infants undergoing 280 imaging sessions (52% male; mean gestational age, 28.3 ± 2.8 weeks; mean birthweight, 1014.5 ± 285.0 g), 36 of 92 (39%) demonstrated ROP. Punctate hyperreflective vitreous opacities were identified in 61 of 92 infants (66%). The presence of punctate hyperreflective vitreous opacities at least once was associated with a diagnosis of ROP (62% vs. 29% without opacities; P = 0.003), maximum ROP stage (P = 0.001), preplus or plus disease (24% vs. 5%; P = 0.005), and type 1 disease (14% vs. 2%; P = 0.03). Among 29 infants (45 imaging sessions) with right-eye punctate hyperreflective vitreous opacities, the vitreous opacity ratio from 2 graders (F1 score, 0.82 ± 0.36; Dice coefficient, 0.97 ± 0.04) correlated with ROP stage (P = 0.02). Tractional vitreous bands on imaging correlated with plus disease status (29% vs. 5% without bands; P = 0.05).
CONCLUSIONS
Punctate hyperreflective vitreous opacities and tractional vitreous bands predict the presence and severity of ROP. Further studies should explore handheld OCT as a noninvasive ROP screening tool.
Topics: Female; Gestational Age; Humans; Infant, Newborn; Male; Ophthalmoscopy; Prospective Studies; Retina; Retinopathy of Prematurity; Severity of Illness Index; Tomography, Optical Coherence; Vitreous Body
PubMed: 32446843
DOI: 10.1016/j.oret.2020.03.027 -
Acta Ophthalmologica Feb 2022Diabetic macular oedema (DME) is considered a chronic inflammatory disease associated with aberrations in many intraocular cytokines. Studies assessing the role of these... (Meta-Analysis)
Meta-Analysis
Diabetic macular oedema (DME) is considered a chronic inflammatory disease associated with aberrations in many intraocular cytokines. Studies assessing the role of these cytokines as biomarkers in the diagnosis and management of DME have demonstrated inconsistent findings. We quantitatively summarized data related to 116 candidate aqueous and vitreous inflammatory cytokines as biomarkers in DME. A systematic search without year limitation was performed up to 19 October 2020. Studies were included if they provided data on aqueous or vitreous cytokine concentrations in patients with DME. Effect sizes were generated as standardized mean differences (SMDs) of cytokine concentrations between patients with DME and controls. Data were extracted from 128 studies that included 4163 study eyes with DME and 1281 control eyes. Concentrations (standard mean difference, 95% confidence interval and p-value) of aqueous IL-6 (1.28, 0.57-2.00, p = 0.004), IL-8 (1.06, 0.74-1.39, p < 0.00001), MCP-1 (1.36, 0.57-2.16, p = 0.0008) and VEGF (1.31, 1.01-1.62, p < 0.00001) and vitreous VEGF (2.27, 1.55-2.99, p < 0.00001) were significantly higher in patients with DME (n = 4163) compared to healthy controls (n = 1281). No differences, failed sensitivity analyses or insufficient data were found between patients with DME and healthy controls for the concentrations of the remaining cytokines. This analysis implicates multiple cytokine biomarker candidates other than VEGF in DME and clarifies previously reported inconsistent associations. As the therapeutic options for DME expand to include multiple agents with multiple targets, it will be critical to manage the treatment burden with tailored therapy that optimizes outcomes and minimizes treatment burden. Intraocular cytokines have the promise of providing a robust individualized assessment of disease status and response to therapy. We have identified key candidate cytokines that may serve as biomarkers in individualized treatment algorithms.
Topics: Aqueous Humor; Biomarkers; Cytokines; Diabetic Retinopathy; Humans; Inflammation; Macular Edema; Vitreous Body
PubMed: 33945678
DOI: 10.1111/aos.14891 -
Eye (London, England) Jul 2023
Meta-Analysis
Topics: Humans; Cytokines; Diabetic Retinopathy; Vitreous Body; Vitrectomy; Diabetes Mellitus
PubMed: 36310184
DOI: 10.1038/s41433-022-02294-x -
Blood Advances Mar 2022Vitreoretinal lymphoma (VRL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL) considered a variant of primary central nervous system lymphoma (PCNSL). The...
Vitreoretinal lymphoma (VRL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL) considered a variant of primary central nervous system lymphoma (PCNSL). The diagnosis of VRL requires examination of vitreous fluid, but cytologic differentiation from uveitis remains difficult. Because of its rarity and the difficulty in obtaining diagnostic material, little is known about the genetic profile of VRL. The purpose of our study was to investigate the mutational profile of a large series of primary and secondary VRL. Targeted next-generation sequencing using a custom panel containing the most frequent mutations in PCNSL was performed on 34 vitrectomy samples from 31 patients with VRL and negative controls with uveitis. In a subset of cases, genome-wide copy number alterations (CNAs) were assessed using the OncoScan platform. Mutations in MYD88 (74%), PIM1 (71%), CD79B (55%), IGLL5 (52%), TBL1XR1 (48%), ETV6 (45%), and 9p21/CDKN2A deletions (75%) were the most common alterations, with similar frequencies in primary (n = 16), synchronous (n = 3), or secondary (n = 12) VRL. This mutational spectrum is similar to MYD88mut/CD79Bmut (MCD or cluster 5) DLBCL with activation of Toll-like and B-cell receptor pathways and CDKN2A loss, confirming their close relationship. OncoScan analysis demonstrated a high number of CNAs (mean 18.6 per case). Negative controls lacked mutations or CNAs. Using cell-free DNA of vitreous fluid supernatant, mutations present in cellular DNA were reliably detected in all cases examined. Mutational analysis is a highly sensitive and specific tool for the diagnosis of VRL and can also be applied successfully to cell-free DNA derived from the vitreous.
Topics: Cell-Free Nucleic Acids; Central Nervous System Neoplasms; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Retinal Neoplasms; Uveitis; Vitreous Body
PubMed: 34448823
DOI: 10.1182/bloodadvances.2021004212 -
Eye (London, England) Feb 2023
Topics: Humans; Vitreous Detachment; Vitreous Body; Retinal Detachment
PubMed: 36138104
DOI: 10.1038/s41433-022-02248-3 -
Journal Francais D'ophtalmologie Nov 2021To compare the expression profiles of various cytokines and chemokines in vitreous samples from patients with retinal detachment (RD) to those from controls and to...
PURPOSE
To compare the expression profiles of various cytokines and chemokines in vitreous samples from patients with retinal detachment (RD) to those from controls and to analyze their association with various clinical features.
METHODS
In this prospective study, undiluted vitreous fluid was obtained from 41 patients with primary RD and 33 controls with macular hole or vitreomacular traction. A multiplex bead immunoassay was performed to determine the expression of 27 inflammatory mediators.
RESULTS
Eleven mediators were significantly upregulated in the vitreous of RD patients compared with controls, including the following: cytokines IL-1ra, IL-6, IL-7, IL-8, IFN-γ; chemokines CCL2, CCL3, CCL4, CXCL10 and CCL11 and growth factor G-CSF. Correlation analyses showed that levels of IL-1ra, CXCL10, CCL11 and G-CSF were positively correlated to the extent of detachment, while those of IL-1ra and CXCL10 were associated with the duration of detachment. There was also a positive association between the concentrations of CXCL10 and CCL11 and preoperative flare values. Additional analysis revealed that flare values and both CXCL10 and CCL11 levels were significantly higher in eyes with grade B or C proliferative vitreoretinopathy (PVR).
CONCLUSION
Our results confirm that RD induces a marked inflammatory response with a complex cytokine network. We identified proteins specifically linked to several clinical features that might contribute to photoreceptor degeneration and PVR-related redetachment. These proteins may represent potential therapeutic targets for improving the anatomical and functional outcomes of RD surgery.
Topics: Cytokines; Humans; Prospective Studies; Retinal Detachment; Vitreoretinopathy, Proliferative; Vitreous Body
PubMed: 34544594
DOI: 10.1016/j.jfo.2021.04.007 -
Scientific Reports Aug 2022The structure of the human vitreous varies considerably because of age-related liquefactions of the vitreous gel. These changes are poorly studied in vivo mainly because...
The structure of the human vitreous varies considerably because of age-related liquefactions of the vitreous gel. These changes are poorly studied in vivo mainly because their high transparency and mobility make it difficult to obtain reliable and repeatable images of the vitreous. Optical coherence tomography can detect the boundaries between the vitreous gel and vitreous fluid, but it is difficult to obtain high resolution images that can be used to convert the images to three-dimensional (3D) images. Thus, the purpose of this study was to determine the shape and characteristics of the vitreous fluid using machine learning-based 3D modeling in which manually labelled fluid areas were used to train deep convolutional neural network (DCNN). The trained DCNN labelled vitreous fluid automatically and allowed us to obtain 3D vitreous model and to quantify the vitreous fluidic cavities. The mean volume and surface area of posterior vitreous fluidic cavities are 19.6 ± 7.8 mm and 104.0 ± 18.9 mm in eyes of 17 school children. The results suggested that vitreous fluidic cavities expanded as the cavities connects with each other, and this modeling system provided novel imaging markers for aging and eye diseases.
Topics: Child; Humans; Machine Learning; Neural Networks, Computer; Tomography, Optical Coherence; Vision Disorders; Vitreous Body
PubMed: 35974072
DOI: 10.1038/s41598-022-17615-z