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Translational Vision Science &... Nov 2023To further establish aqueous humor (AH) as a clinically suitable source of protein biomarkers in retinal diseases by evaluating the correlation of a large panel of...
PURPOSE
To further establish aqueous humor (AH) as a clinically suitable source of protein biomarkers in retinal diseases by evaluating the correlation of a large panel of proteins between AH, vitreous humor (VH), and serum (SE).
METHODS
We enrolled 60 subjects (eyes) with various non-infectious retinal diseases. AH, VH, and SE proteins were analyzed using the Olink Target 96 platform (1196 protein assays in total). We compared these three matrices in terms of quantification overlap, principal component analysis, and correlation.
RESULTS
In the AH, VH, and SE samples, 841, 917, and 1133 proteins, respectively, were consistently quantified above the limit of detection in more than 30% of patients. AH and VH shared 812 of these proteins. AH and VH samples overlapped along principal component 1, but SE samples were distinct. We identified 490 proteins with significant (false discovery rate [FDR]-adjusted P < 0.05) and relevant correlations (correlation coefficient > 0.5) between AH and VH, compared to only 33 and 40 proteins for VH and SE and for AH and SE, respectively.
CONCLUSIONS
Due to a close correlation between protein concentrations in the AH and VH and a clear difference from the SE, AH has the potential to serve as a substitute for VH and may hold significance in identifying protein biomarkers and novel targets related to retinal diseases.
TRANSLATIONAL RELEVANCE
This study further supports AH as a clinically suitable source of protein biomarkers in retinal diseases. In addition, the identified AH and VH correlations can inform the selection of protein biomarker candidates in future translational research.
Topics: Humans; Blood Proteins; Retinal Diseases; Aqueous Humor; Retina; Biomarkers
PubMed: 37930665
DOI: 10.1167/tvst.12.11.9 -
PloS One 2024To investigate relationship between vitreous interleukin-6 levels and vitreous particles findings on widefield optical coherence tomography in posterior uveitis.
PURPOSE
To investigate relationship between vitreous interleukin-6 levels and vitreous particles findings on widefield optical coherence tomography in posterior uveitis.
METHODS
This retrospective study examined vitreous inflammatory cells (hyperreflective particles) of posterior uveitis on widefield optical coherence tomography (WOCT). We examined the number of hyperreflective particles (possibility of vitreous inflammatory cells) observed on WOCT and the correlations with interleukin-6 (IL-6) levels. The relationship between vitreous IL-6 levels and image findings from WOCT from 37 eyes (34 patients) with posterior uveitis were analyzed. Mean patient age was 63.4±15.7 years. (Mean± standard deviation) IL-6 concentration in vitreous humor was 79.9±7380.9 pg/mL Uveitis was infectious in 9 cases and non-infectious in 28 cases with multiplex polymerase chain reaction system. We measured the number and size of vitreous cells in the posterior vitreous, defined as the space between the upper vitreous and the internal limiting membrane on WOCT at the macular, upper, and lower regions. Image analysis software was also used for cell counting.
RESULTS
A strong correlation was seen between human and software counts. Pearson's correlation coefficient (PCC) was performed to compare categorial variables (on macular +0.866; upper cavity +0.713; lower cavity +0.568; total vitreous cavity +0.834; P<0.001 each). IL-6 levels correlated with both vitreous cell counts and cell counts observed on macular WOCT (human-counted group +0.339, P = 0.04; software-counted group +0.349, P = 0.03). Infectious uveitis showed higher IL-6 levels (P = 0.016) and high cell counts compared with non-infectious uveitis (P = 0.04).
CONCLUSIONS
Vitreous number of hyperreflective particles (cells) findings on WOCTcorrelated well with human and software cell counts. Vitreous cells findings on WOCT also correlated with IL-6 concentrations on macular.
Topics: Humans; Middle Aged; Aged; Interleukin-6; Retrospective Studies; Tomography, Optical Coherence; Uveitis, Posterior; Uveitis; Retina
PubMed: 38232093
DOI: 10.1371/journal.pone.0297201 -
Gels (Basel, Switzerland) Oct 2023To treat certain vitreoretinal diseases, the vitreous body, a hydrogel composed of mostly collagen and hyaluronic acid, must be removed. After vitrectomy surgery, the...
Forward Light Scattering of First to Third Generation Vitreous Body Replacement Hydrogels after Surgical Application Compared to Conventional Silicone Oils and Vitreous Body.
To treat certain vitreoretinal diseases, the vitreous body, a hydrogel composed of mostly collagen and hyaluronic acid, must be removed. After vitrectomy surgery, the vitreous cavity is filled with an endotamponade. Previously, pre-clinical hydrogel-based vitreous body substitutes either made from uncrosslinked monomers (1st generation), preformed crosslinked polymers (2nd generation), or in situ gelating polymers (3rd generation) have been developed. Forward light scattering is a measure of Stray light induced by optical media, when increased, causing visual disturbance and glare. During pinhole surgery, the hydrogels are injected into the vitreous cavity through a small 23G-cannula. The aim of this study was to assess if and to what extent forward light scattering is induced by vitreous body replacement hydrogels and if Stray light differs between different generations of vitreous body hydrogel replacements due to the different gelation mechanisms and fragmentation during injection. A modified C-Quant setup was used to objectively determine forward light scattering. In this study, we found that the 1st and 3rd generation vitreous body replacements show very low stray light levels even after injection (2.8 +/- 0.4 deg/sr and 0.2 +/- 0.2 deg/sr, respectively) as gel fragmentation and generation of interfaces is circumvented. The 2nd generation preformed hydrogels showed a permanent increase in stray light after injection that will most likely lead to symptoms such as glare when used in patients (11.9 +/- 0.9 deg/sr). Stray light of the 2nd generation hydrogels was 3- and 2-fold increased compared to juvenile and aged vitreous bodies, respectively. In conclusion, this significant downside in the forward light scattering of the 2nd generation hydrogels should be kept in mind when developing vitreous body replacement strategies, as any source of stray light should be minimized in patients with retinal comorbidities.
PubMed: 37888410
DOI: 10.3390/gels9100837 -
BMC Ophthalmology May 2024Primary vitreous cyst is a clinical variant delineated by the existence of a vesicle within the vitreous cavity from birth. This particular disease tends to be uncommon,...
BACKGROUND
Primary vitreous cyst is a clinical variant delineated by the existence of a vesicle within the vitreous cavity from birth. This particular disease tends to be uncommon, and the underlying mechanisms contributing to its pathogenesis remain obscure.
CASE PRESENTATION
A 37-year-old male patient manifested blurry vision and floaters in his right eye, a symptomology first noticed three months prior. Upon slit-lamp examination, a pigmented, round, 1 papilla diameter-sized mass was discerned floating in the vitreous. A meticulous examination of the floaters was conducted using an array of multimodal imaging techniques. Other potential conditions, including cysticercosis, toxoplasmosis, and tumors, were conclusively excluded through comprehensive diagnostic tests such as blood examinations, liver ultrasound, and cranial magnetic resonance imaging (MRI), resulting in the diagnosis of a primary vitreous cyst. The patient did not report any other discomforts and did not receive any subsequent interventions or treatments.
CONCLUSION
We furnish an exhaustive case report of a patient diagnosed with a primary vitreous cyst. The incorporation of multimodal images in the characterization of the disease anticipates facilitating an enriched comprehension by medical practitioners.
Topics: Humans; Male; Adult; Cysts; Vitreous Body; Multimodal Imaging; Eye Diseases; Magnetic Resonance Imaging; Tomography, Optical Coherence
PubMed: 38773513
DOI: 10.1186/s12886-024-03482-x -
Experimental Eye Research Oct 2023Although mouse models are widely used in retinal drug development, pharmacokinetics in mouse eye is poorly understood. In this study, we applied non-invasive in vivo...
Although mouse models are widely used in retinal drug development, pharmacokinetics in mouse eye is poorly understood. In this study, we applied non-invasive in vivo fluorophotometry to study pharmacokinetics of intravitreal fluorescein sodium (molecular weight 0.38 kDa) and fluorescein isothiocyanate-dextran (FD-150; molecular weight 150 kDa) in mice. Intravitreal half-lives of fluorescein and FD-150 in mouse eyes were 0.53 ± 0.06 h and 2.61 ± 0.86 h, respectively. These values are 8-230 times shorter than the elimination half-lives of similar compounds in the human vitreous. The apparent volumes of distribution in the mouse vitreous were close to the anatomical volume of the mouse vitreous (FD-150, 5.1 μl; fluorescein, 9.6 μl). Dose scaling factors were calculated from mouse to rat, rabbit, monkey and human translation. Based on pharmacokinetic modelling and compound concentrations in the vitreous and anterior chamber, fluorescein is mainly eliminated posteriorly across blood-retina barrier, but FD-150 is cleared via aqueous humour outflow. The results of this study improve the knowledge of intravitreal pharmacokinetics in mouse and facilitate inter-species scaling in ocular drug development.
Topics: Mice; Rats; Humans; Animals; Rabbits; Vitreous Body; Retina; Blood-Retinal Barrier; Fluorescein; Anterior Chamber; Intravitreal Injections
PubMed: 37657528
DOI: 10.1016/j.exer.2023.109638 -
Ophthalmology and Therapy Dec 2023The factors related to the ocular penetration of drugs after the administration of eye drops in humans have not been examined in detail. Therefore, this study assessed...
INTRODUCTION
The factors related to the ocular penetration of drugs after the administration of eye drops in humans have not been examined in detail. Therefore, this study assessed the influence of patient factors on the intraocular penetration of eye drops.
METHODS
A pooled analysis was performed on the data of 42 participants from three studies to evaluate the ocular pharmacokinetics in humans after the topical application of brimonidine-related eye drops. The patients were scheduled for vitrectomy and received brimonidine-related eye drops (0.1% brimonidine tartrate ophthalmic solution, 0.1% brimonidine tartrate and 0.5% timolol fixed-combination ophthalmic solution, or 0.1% brimonidine tartrate and 1% brinzolamide fixed-combination suspension) twice daily for 1 week. We analyzed the effects of patient factors (sex, the presence or absence of lens, age, corneal thickness, corneal endothelial cell density, tear secretion, eye axial length, height, weight and body mass index [BMI]) on brimonidine, timolol and brinzolamide concentrations in the aqueous and vitreous humor after topical application.
RESULTS
The drug concentrations in the aqueous and vitreous humor were not significantly different, regardless of sex or the presence or absence of lens. Age correlated positively with brimonidine (r = 0.3948, p = 0.012) and brinzolamide (r = 0.6809, p = 0.030) concentrations in the aqueous humor; the correlation with timolol showed a trend towards significance (r = 0.6425, p = 0.086). Corneal thickness, corneal endothelial cell density, tear secretion, eye axial length, height and BMI did not correlate with the drug concentrations in the aqueous or vitreous humor. Timolol concentration in the vitreous humor was negatively correlated with weight (r = - 0.8333, p = 0.010).
CONCLUSION
The findings of this study emphasize the necessity of considering individual differences in ocular pharmacokinetics during drug therapy (formulation design of the eye drops and dose regimen).
PubMed: 37676633
DOI: 10.1007/s40123-023-00794-x -
Translational Vision Science &... May 2024Extracellular vesicles (EVs) are messenger pigeons of the cells that communicate about cellular microenvironment. In this study, we evaluated the expression of C8α and...
PURPOSE
Extracellular vesicles (EVs) are messenger pigeons of the cells that communicate about cellular microenvironment. In this study, we evaluated the expression of C8α and calpain-2 in EVs from vitreous of patients with bacterial endophthalmitis to assess its utility as a diagnostic marker.
METHODS
EVs were isolated from vitreous of patients with bacterial endophthalmitis (culture positive and culture negative) and noninfectious control by exosome isolation reagent and characterized, and the levels of C8α and calpain-2 was assessed by enzyme-linked immunosorbent assay in isolated EVs and direct vitreous. The receiver operating characteristic curve was generated to assess the diagnostic performance.
RESULTS
Scanning electron microscopy (SEM) and dynamic light scattering (DLS) confirmed the presence of EVs having a diameter (nm) of 275.2 ± 93, 92 ± 22, and 77.28 ± 12 in culture-positive (CP), culture-negative (CN), and control respectively. The expression level (ng/mL) of C8α in the EVs obtained from CP was 144 ± 22 and CN was 31.2 ± 9.8, which was significantly higher (P < 0.01) than control 3.7 ± 2.4. Interestingly, C8α is not expressed directly in the vitreous of CN and controls. Calpain-2 was significantly downregulated (P ≤ 0.0001) in CP (0.94 ± 0.16) and CN (0.70 ± 0.14) than control. The sensitivity and specificity of 1 for C8α and calpain-2 in the EVs implied that its diagnostic accuracy was significant.
CONCLUSIONS
This study showed that the EV proteins C8α and calpain-2 could be suitable diagnostic markers for endophthalmitis. However, the presence of C8α in the EVs of CN samples but not in direct vitreous promises EVs as the future of diagnostics.
TRANSLATIONAL RELEVANCE
Expression levels of EV-calpain-2 and EV-C8α could diagnose CN bacterial endophthalmitis.
Topics: Calpain; Humans; Vitreous Body; Endophthalmitis; Extracellular Vesicles; Biomarkers; Male; Female; Middle Aged; Enzyme-Linked Immunosorbent Assay; Aged; Eye Infections, Bacterial; ROC Curve; Microscopy, Electron, Scanning; Adult
PubMed: 38767905
DOI: 10.1167/tvst.13.5.14 -
Investigative Ophthalmology & Visual... Jul 2023The relative importance of genetic factors in common vitreomacular interface (VMI) abnormalities is unknown. The aim of this classical twin study is to determine the...
PURPOSE
The relative importance of genetic factors in common vitreomacular interface (VMI) abnormalities is unknown. The aim of this classical twin study is to determine the prevalence case wise concordance between monozygotic and dizygotic twin pairs, and heritability of common VMI abnormalities, including epiretinal membrane (ERM), posterior vitreous detachment (PVD), vitreomacular adhesion (VMA), vitreomacular traction (VMT), lamellar macular holes (LMHs), and full-thickness macular holes (FTMHs).
METHODS
This is a single-center, cross-sectional classical twin study of 3406 TwinsUK participants over the age of 40 years who underwent spectral domain macular optical coherence tomography (SD-OCT) scans which were graded for signs of VMI abnormalities. Case wise concordance was calculated and the heritability of each VMI abnormality was estimated using OpenMx structural equation modeling.
RESULTS
In this population (mean age = 62.0 years [SD = 10.4 years], range = 40-89 years) the overall prevalence of ERM was 15.6% (95% confidence interval [CI] = 14.4-16.9) and increased with age, posterior vitreous detachment affected 21.3% (20.0-22.7), and VMA was diagnosed in 11.8% (10.8-13.0). Monozygotic twins were more concordant for all traits than dizygotic twins, and age, spherical equivalent refraction (SER), and lens status-adjusted heritability was estimated at 38.9% (95% CI = 33.6-52.8) for ERM, 53.2% (95% CI = 41.8-63.2) for PVD, and 48.1% (95% CI = 33.6-58) for VMA.
CONCLUSIONS
Common VMI abnormalities are heritable and therefore have an underlying genetic component. Given the sight-threatening potential of VMI abnormalities, further genetic studies, such as genomewide association studies, would be useful to identify genes and pathways implicated in their pathogenesis.
Topics: Humans; Adult; Middle Aged; Aged; Aged, 80 and over; Vitreous Detachment; Retinal Perforations; Vitreous Body; Prevalence; Cross-Sectional Studies; Retinal Diseases; Epiretinal Membrane; Orbital Diseases; Tomography, Optical Coherence; Retrospective Studies
PubMed: 37428499
DOI: 10.1167/iovs.64.10.9 -
Cureus Feb 2024Purpose 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...
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 r=0.175, p-value=0.488 for CRT, and r=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.
PubMed: 38533176
DOI: 10.7759/cureus.54862 -
Scientific Reports Mar 2024The aim of this study was to investigate the anatomical and physiological ocular parameters in adolescents with myopia and to examine the relations between refractive...
The aim of this study was to investigate the anatomical and physiological ocular parameters in adolescents with myopia and to examine the relations between refractive error (SER), ocular biometry, body size and flexibility parameters in myopic adolescents. A cross-sectional study of 184 myopic adolescents, aged 15 to 19 years was conducted. Refractive error and corneal curvature measures of the eye were evaluated using an autorefractometer under cycloplegia. Central corneal thickness was determined by contact pachymetry. The ocular axial length, anterior and vitreous chamber depth, and lens thickness were measured using A-scan biometry ultrasonography. Height and body weight were measured according to a standardized protocol. Body mass index (BMI) was subsequently calculated. Beighton scale was used to measure joint flexibility. Body stature was positively correlated with ocular axial length (r = 0.39, p < 0.001) and vitreous chamber depth (r = 0.37, p < 0.001). There was a negative correlation between height and SER (r = - 0.46; p < 0.001). Beighton score and body weight had weak positive correlations with axial length and vitreous chamber depth, and a weak negative correlation with SER. A significantly more negative SER was observed in the increased joint mobility group (p < 0.05; U = 5065.5) as compared to normal joint mobility group: mean - 4.37 ± 1.85 D (median - 4.25; IQR - 6.25 to - 3.25 D) and mean - 3.72 ± 1.66 D (median - 3.50; IQR - 4.75 to - 2.25 D) respectively. There was a strong association between height and axial length, as well as SER. Higher degree of myopia significantly correlated with greater Beighton score (increased joint mobility).
Topics: Adolescent; Humans; Cross-Sectional Studies; Eye; Myopia; Refractive Errors; Biometry; Body Weight; Anterior Eye Segment; Refraction, Ocular; Anterior Chamber; Axial Length, Eye
PubMed: 38514709
DOI: 10.1038/s41598-024-57347-w