Analysis of multiple cytokines in aqueous humor of patients with idiopathic macular hole

Abstract Background Idiopathic macular hole is a common type of ophthalmic disease, and its pathogenesis is unknown. At present, little research about the pathogenesis, especially the immune mechanism, of idiopathic macular hole has been reported. To provide scientific guidance for the treatment and prognosis of idiopathic macular holes, this study examined and analyzed multiple cytokines levels in aqueous humor from patients with idiopathic macular hole. Methods Thirty-eight subjects were divided into cataract control group (n = 17) and idiopathic macular hole group (n = 21). The levels of 48 cytokines in aqueous humor were detected by multiple magnetic beads immunization. Results There were significant differences in cytokine levels in aqueous humor from idiopathic macular holes patients compared with the cataract control group. For example, HGF (p = 0.0001), GM-CSF (p = 0.0111), and IFN-γ (p = 0.0120) were significantly up-regulated, while TNF-α (p = 0.0032), GRO-α (p < 0.0001), and MIF (p < 0.0001) were significantly down-regulated. GM-CSF showed a significant positive correlation with IL-1 (r = 0.67904, p < 0.001), IL-4 (r = 0.76017, p < 0.001), and IFN-γ (r = 0.59922, p = 0.004097). Moreover, NGF and HGF also showed a significant positive correlation (r = 0.64951, p = 0.001441). Conclusion Patients with idiopathic macular hole could exhibit significant variation of the immune reaction in aqueous humor after the disease, including the recruitment of immune cells and the regulation of cytokine expression. This study also implied that it is not rigorous to use macular hole as the control in current studies on aqueous humor cytokines in ophthalmic diseases.

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Analysis of multiple cytokines in aqueous humor of patients with idiopathic macular hole

10.21203/rs.3.rs-25621/v2 ◽

2020 ◽

Author(s):

Heping Wang ◽

Yuqi Li ◽

Song Han ◽

Tongtong Niu

Keyword(s):

Growth Factor ◽

Aqueous Humor ◽

Control Group ◽

Gm Csf ◽

Macular Holes ◽

Cytokine Levels ◽

Idiopathic Macular Holes ◽

Ifn Γ ◽

Hepatocyte Growth ◽

Experimental Group

Abstract Background: Idiopathic macular holes are common ophthalmic manifestations with unknown pathogenesis. Thus far, there has been minimal research regarding the causes of idiopathic macular holes, especially with respect to the underlying immune mechanism. To provide clarity regarding the treatment and prognosis of idiopathic macular holes, specifically regarding the levels of cytokines in affected patients, this study examined and analyzed multiple cytokine levels in aqueous humor from patients with idiopathic macular holes. Methods: This comparative cross-sectional study included 38 patients in two groups: a cataract control group (n=17) and an idiopathic macular hole group (n=21). The levels of 48 cytokines in aqueous humor were detected by multiplex analysis with antibody-coupled magnetic beads. The Kolmogorov–Smirnov test was used to check whether the data were normally distributed; Student’s t-test and the Mann–Whitney U test were used to assess differences in cytokine levels between the two groups. Spearman correlation analysis was used to assess relationships among cytokine levels in the experimental group. Signaling pathways containing cytokines with significantly different expression in the experimental group were identified. Results: There were significant differences in aqueous humor cytokine levels between patients with idiopathic macular holes and patients in the cataract control group. Notably, hepatocyte growth factor (p=0.0001), GM-CSF (p=0.0111), and IFN-γ (p=0.0120) were significantly upregulated in the experimental group , while TNF-α (p=0.0032), GRO-α (p<0.0001), and MIF (p<0.0001) were significantly downregulated in the experimental group. Furthermore, the GM-CSF level showed significant positive correlations with levels of IL-1 (r=0.67904, p<0.001), IL-4 (r=0.76017, p<0.001), and IFN-γ (r=0.59922, p=0.004097) in the experimental group. Moreover, the levels of nerve growth factor and hepatocyte growth factor showed a significant positive correlation (r=0.64951, p=0.001441) in the experimental group. Conclusions: Patients with idiopathic macular holes showed significant variation in aqueous humor immune response after the onset of hole formation, including the recruitment of immune cells and regulation of cytokine expression. Our findings also suggest that it is not appropriate to use patients with macular holes as the control group in studies of aqueous humor cytokine levels in ophthalmic diseases.

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Analysis of multiple cytokines in aqueous humor of patients with idiopathic macular hole

10.21203/rs.3.rs-25621/v4 ◽

2021 ◽

Author(s):

Heping Wang ◽

Yuqi Li ◽

Song Han ◽

Tongtong Niu

Keyword(s):

Growth Factor ◽

Aqueous Humor ◽

Control Group ◽

Gm Csf ◽

Macular Holes ◽

Cytokine Levels ◽

Idiopathic Macular Holes ◽

Ifn Γ ◽

Hepatocyte Growth ◽

Experimental Group

Abstract Background: Idiopathic macular holes are common ophthalmic manifestations with unknown pathogenesis. Thus far, there has been minimal research regarding the causes of idiopathic macular holes, especially with respect to the underlying immune mechanism. To provide clarity regarding the treatment and prognosis of idiopathic macular holes, specifically regarding the levels of cytokines in affected patients, this study examined and analyzed multiple cytokine levels in aqueous humor from patients with idiopathic macular holes.Methods: This comparative cross-sectional study included 38 patients in two groups: a cataract control group (n=17) and an idiopathic macular hole group (n=21). The levels of 48 cytokines in aqueous humor were detected by multiplex analysis with antibody-coupled magnetic beads. The Kolmogorov–Smirnov test was used to check whether the data were normally distributed; Student’s t-test and the Mann–Whitney U test were used to assess differences in cytokine levels between the two groups. Spearman correlation analysis was used to assess relationships among cytokine levels in the experimental group. Signaling pathways containing cytokines with significantly different expression in the experimental group were identified.Results: There were significant differences in aqueous humor cytokine levels between patients with idiopathic macular holes and patients in the cataract control group. Notably, hepatocyte growth factor (p=0.0001), GM-CSF (p=0.0111), and IFN-γ (p=0.0120) were significantly upregulated in the experimental group, while TNF-α (p=0.0032), GRO-α (p<0.0001), and MIF (p<0.0001) were significantly downregulated in the experimental group. Furthermore, the GM-CSF level showed significant positive correlations with levels of IL-1 (r=0.67904, p<0.001), IL-4 (r=0.76017, p<0.001), and IFN-γ (r=0.59922, p=0.004097) in the experimental group. Moreover, the levels of nerve growth factor and hepatocyte growth factor showed a significant positive correlation (r=0.64951, p=0.001441) in the experimental group.Conclusions: Patients with idiopathic macular holes showed significant variation in aqueous humor immune response after the onset of hole formation, including the recruitment of immune cells and regulation of cytokine expression. Our findings also suggest that it is not appropriate to use patients with macular holes as the control group in studies of aqueous humor cytokine levels in ophthalmic diseases.

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Analysis of multiple cytokines in aqueous humor of patients with idiopathic macular hole

10.21203/rs.3.rs-25621/v3 ◽

2020 ◽

Author(s):

Heping Wang ◽

Yuqi Li ◽

Song Han ◽

Tongtong Niu

Keyword(s):

Growth Factor ◽

Aqueous Humor ◽

Control Group ◽

Gm Csf ◽

Macular Holes ◽

Cytokine Levels ◽

Idiopathic Macular Holes ◽

Ifn Γ ◽

Hepatocyte Growth ◽

Experimental Group

Abstract Background: Idiopathic macular holes are common ophthalmic manifestations with unknown pathogenesis. Thus far, there has been minimal research regarding the causes of idiopathic macular holes, especially with respect to the underlying immune mechanism. To provide clarity regarding the treatment and prognosis of idiopathic macular holes, specifically regarding the levels of cytokines in affected patients, this study examined and analyzed multiple cytokine levels in aqueous humor from patients with idiopathic macular holes.Methods: This comparative cross-sectional study included 38 patients in two groups: a cataract control group (n=17) and an idiopathic macular hole group (n=21). The levels of 48 cytokines in aqueous humor were detected by multiplex analysis with antibody-coupled magnetic beads. The Kolmogorov–Smirnov test was used to check whether the data were normally distributed; Student’s t-test and the Mann–Whitney U test were used to assess differences in cytokine levels between the two groups. Spearman correlation analysis was used to assess relationships among cytokine levels in the experimental group. Signaling pathways containing cytokines with significantly different expression in the experimental group were identified.Results: There were significant differences in aqueous humor cytokine levels between patients with idiopathic macular holes and patients in the cataract control group. Notably, hepatocyte growth factor (p=0.0001), GM-CSF (p=0.0111), and IFN-γ (p=0.0120) were significantly upregulated in the experimental group, while TNF-α (p=0.0032), GRO-α (p<0.0001), and MIF (p<0.0001) were significantly downregulated in the experimental group. Furthermore, the GM-CSF level showed significant positive correlations with levels of IL-1 (r=0.67904, p<0.001), IL-4 (r=0.76017, p<0.001), and IFN-γ (r=0.59922, p=0.004097) in the experimental group. Moreover, the levels of nerve growth factor and hepatocyte growth factor showed a significant positive correlation (r=0.64951, p=0.001441) in the experimental group.Conclusions: Patients with idiopathic macular holes showed significant variation in aqueous humor immune response after the onset of hole formation, including the recruitment of immune cells and regulation of cytokine expression. Our findings also suggest that it is not appropriate to use patients with macular holes as the control group in studies of aqueous humor cytokine levels in ophthalmic diseases.

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IMMMUNE MEDIATORS IN IDIOPATHIC UVEITIS

10.1101/2021.08.04.455093 ◽

2021 ◽

Author(s):

Marie-Helene Errera ◽

Ana Pratas ◽

Sylvain Fisson ◽

Thomas Manicom ◽

Marouane Boubaya ◽

...

Keyword(s):

Aqueous Humor ◽

Unsupervised Classification ◽

Control Group ◽

Serum Samples ◽

Gm Csf ◽

Cytokines And Chemokines ◽

Age Related ◽

Order Of Magnitude ◽

Ifn Γ ◽

Endothelial Growth Factor

To investigate which cytokines, chemokines and growth factors are involved in the immunopathogenesis of idiopathic uveitis, and whether cytokine proﬁles are associated with. Serum and aqueous humor (AH) samples of 75 patients with idiopathic uveitis were analyzed by multiplex immunoassay. Infectious controls consisted of 16 patients with ocular toxoplasmosis all conﬁrmed by intraocular ﬂuid analyses. Noninfectious controls consisted of 7 patients with Behçet disease related uveitis and 15 patients with sarcoidosis related uveitis. The control group consisted of AH and serum samples from 47 noninﬂammatory control patients with age-related cataract. In each sample, 27 immune mediators ± IL-21 and IL-23 were measured. In idiopathic uveitis, 13 of the 29 mediators, including most proinﬂammatory and vascular mediators such as IL-6, IL-8, IL-12, G-CSF, GM-CSF, MCP-1, IP-10, TNF-α and VEGF, were signiﬁcantly elevated in the aqueous humor when compared to all controls. Moreover, IL-17, IP-10, and IL-21, were signiﬁcantly elevated in the serum when compared to all controls. We clustered 4 subgroups of idiopathic uveitis using a statistical analysis of hierarchical unsupervised classification, characterized by the order of magnitude of concentrations of intraocular cytokines. The pathogenesis of idiopathic uveitis is characterized by the presence of predominantly proinﬂammatory cytokines and chemokines and vascular endothelial growth factor with high expression levels as compared to other causes of uveitis. There are indications for obvious Th-1/ IL21-Th17 pathways but also IL9-Th9 and increased IFN-γ-inducing cytokine (IL12) and IFN-γ-inducible CXC chemokine (IP-10). The combined data suggest that immune mediator expression is different among idiopathic uveitis. This study suggests various clusters among the idiopathic uveitis group rather than one speciﬁc uveitis entity.

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Autologous internal limiting membrane transplant for recurrent idiopathic macular holes

European Journal of Ophthalmology ◽

10.1177/1120672120906391 ◽

2020 ◽

pp. 112067212090639 ◽

Cited By ~ 1

Author(s):

Tommaso Rossi ◽

Carlandrea Trillo ◽

Guido Ripandelli

Keyword(s):

Visual Acuity ◽

Macular Hole ◽

Outer Segment ◽

Internal Limiting Membrane ◽

Control Group ◽

Closure Rate ◽

Internal Limiting Membrane Peeling ◽

Membrane Peeling ◽

Macular Holes ◽

Idiopathic Macular Holes

Purpose: To report a series of recurrent idiopathic macular holes treated by means of a free autologous internal limiting membrane flap and compare visual and anatomic results to a control group undergoing further internal limiting membrane peeling and novel gas tamponade. Methods: Retrospective surgical series of 15 consecutive patients receiving autologous internal limiting membrane flap compared to 14 patients operated on for internal limiting membrane peeling enlargement. Autologous internal limiting membrane flap was created after brilliant blue G staining, internal limiting membrane lifting, perfluorocarbon bubble injection and creation of a wide internal limiting membrane free flap translocated underneath perfluorocarbon liquid, to the macular hole bed. Both groups were tamponated with 20% SF6 and positioned face down for 4 h a day for 3 days. Results: Macular hole closed in 14/15 (93.3%) patients of the autologous internal limiting membrane group and 9/14 (64.2%) controls (p < 0.05). Visual acuity increased from 0.05 ± 0.03 to 0.23 ± 0.13 Snellen in the autologous internal limiting membrane group and from 0.05 ± 0.03 to 0.14 ± 0.10 Snellen of controls (p < 0.05 for both). Vision of the autologous internal limiting membrane group improved more than controls at 1 month (p = 0.043) and 3 months (p = 0.045). Inner segment/outer segment interruption at 3 months was smaller in the autologous internal limiting membrane group than controls, reducing from 1230 ± 288 µm at baseline to 611 ± 245 and 547 ± 204 µm at 3 months versus 1196 ± 362, 745 ± 222 and 705 ± 223 µm, respectively (p < 0.05). Conclusion: Autologous internal limiting membrane flap can effectively close recurrent idiopathic macular holes with a higher closure rate, smaller residual inner segment/outer segment line interruption and higher visual acuity at 3 months than previous standard of care.

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Anterior chamber aqueous flare is not a predictor for surgical closure of full-thickness idiopathic macular holes

European Journal of Ophthalmology ◽

10.1177/1120672119843283 ◽

2019 ◽

Vol 30 (5) ◽

pp. 1127-1134 ◽

Cited By ~ 1

Author(s):

Friederike Schaub ◽

Philip Enders ◽

Paula Scholz ◽

Philipp S Müther ◽

Sascha Fauser ◽

...

Keyword(s):

Anterior Chamber ◽

Macular Hole ◽

Internal Limiting Membrane ◽

Idiopathic Macular Hole ◽

Internal Limiting Membrane Peeling ◽

Aqueous Flare ◽

Macular Holes ◽

Pars Plana ◽

Idiopathic Macular Holes ◽

Linear Diameter

Purpose: To investigate the predictive value of preoperative anterior chamber aqueous flare levels measured by laser flare photometry for surgical success of idiopathic macular holes in addition to preoperative anatomic characteristics. Methods: Records of 105 consecutive eyes with full-thickness idiopathic macular holes which underwent pars plana vitrectomy with internal limiting membrane peeling and sulfur hexafluoride 20% (SF620%) endotamponade were reviewed retrospectively. All patients underwent preoperative measurements of anterior chamber aqueous flare and anatomical idiopathic macular hole characteristics evaluated by optical coherence tomography: macular hole inner opening diameter, macular hole minimum linear diameter, macular hole base diameter, and macular hole height. Best-corrected visual acuity results were recorded pre- and postoperatively. Results: In 17 (16.2%) of 105 eyes primary closure of idiopathic macular hole failed, whereas in 88 eyes (83.8%) closure was achieved. Between both groups, preoperative macular hole minimum linear diameter (p = 0.001) and macular hole inner opening diameter (p = 0.006) were statistically different. Failure rates were significantly lower in eyes with macular hole minimum linear diameter < 400 µm (7.4% vs 32.4%; p = 0.013) and preoperative macular hole minimum linear diameter showed moderate correlation with pre- and postoperative best-corrected visual acuity results (r = 0.512; p < 0.001; r = 0.612; p < 0.001). Mean anterior chamber aqueous flare of 11.5 ± 9.9 pc/ms in eyes with anatomical closure and 11.8 ± 6.4 pc/ms in unclosed cases was comparable (p = 0.28) and did not correlate with anatomical or functional results. Conclusion: Eyes with idiopathic macular hole ⩾ 400 µm in size have a significantly higher failure rate following standardized pars plana vitrectomy with internal limiting membrane peeling and SF620% endotamponade. Preoperative macular hole minimum linear diameter and macular hole inner opening diameter seem to be associated with surgical outcome in idiopathic macular hole, whereas anterior chamber aqueous flare level does not provide additional predictive value.

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Optical Coherence Tomography Findings in Idiopathic Macular Holes

Journal of Ophthalmology ◽

10.1155/2011/928205 ◽

2011 ◽

Vol 2011 ◽

pp. 1-4 ◽

Cited By ~ 5

Author(s):

Lynn L. Huang ◽

David H. Levinson ◽

Jonathan P. Levine ◽

Umar Mian ◽

Irena Tsui

Keyword(s):

Optical Coherence Tomography ◽

Macular Hole ◽

Clinical Assessment ◽

Chart Review ◽

Subretinal Fluid ◽

Optical Coherence ◽

Cross Sectional ◽

Macular Holes ◽

Idiopathic Macular Holes ◽

Intraretinal Cysts

Purpose. To describe the characteristics of idiopathic macular holes (MH) on optical coherence tomography (OCT) and correlate OCT with clinical assessment.Design. Cross-sectional chart review and OCT assessment.Participants. Sixty-seven eyes with a clinically diagnosed idiopathic MH with available OCT data.Methods. A retrospective chart review and OCT assessment.Results. Based on OCT grading, 40 eyes had a full-thickness macular hole (FTMH) and 21 eyes had a lamellar macular hole (LMH). Clinical exam and OCT assessment agreed in 53 (87%) eyes when assessing the extent of MH. Six eyes (14.6%) in the FTMH group, and 3 eyes in the LMH group (14.3%) had persistent vitreomacular traction. Thirty-seven eyes (92.5%) in the FTMH group and 11 eyes (52.4%) in the LMH group had associated intraretinal cysts. Two eyes (5.0%) in the FTMH group and zero eyes in the LMH group had subretinal fluid. Intraretinal cysts were found to be more frequently associated with FTMH than with LMH (P<0.001).Conclusion. This paper described OCT findings in a group of patients with clinically diagnosed MH. A high level of correlation between clinical assessment and OCT findings of LMH and FTMH was observed, and intraretinal cysts were often present in FTMH.

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Morphofunctional analysis of the retina in the surgical treatment of idiopathic macular holes

Modern technologies in ophtalmology ◽

10.25276/2312-4911-2021-3-48-52 ◽

2021 ◽

pp. 48-52

Author(s):

A.S. Zotov ◽

◽

A.S. Balalin ◽

S.V. Balalin ◽

S.M. Purshak ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Surgical Treatment ◽

Macular Hole ◽

Practical Importance ◽

Functional Results ◽

Hole Diameter ◽

Optical Coherence ◽

Macular Holes ◽

Idiopathic Macular Holes ◽

Morphofunctional Analysis

Purpose. To evaluate the role of microperimetry and optical coherence tomography (OCT) in the morphofunctional analysis of the retina after surgical treatment of idiopathic macular holes (IMH). Materials and methods. A retrospective study of 33 patient's treatment results (33 eyes) with IMH was carried out. All patients underwent minimally invasive with 25G or 27G vitrectomy. Best corrected visual acuity (BCVA), macular photosensitivity, fixation stability, macular neuroepithelial (NE) volume and minimal macular hole diameter were analyzed. Follow-up period: 6 months. Results. A complete closure of the macular hole was achieved in all cases post-op. The patients had reliable improvement of BCVA, retinal photosensitivity and decrease of macular NE volume. Based on a multifactor correlation analysis with the purpose to predict the results of surgical treatment, the dependence of post-op BCVA on the pre-op photosensitivity of the retina and the minimal diameter of the macular hole was revealed. Conclusions. Microperimetry and OCT are modern non-invasive research methods allowing to estimate anatomical and functional results of surgical IMH treatment. The study of retinal photosensitivity in the macula and minimal macular hole diameter pre-op allows to predict post-op BCVA, which has a practical importance. Keywords: idiopathic macular hole, vitrectomy, microperimetry, optical coherence tomography.

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Anti carbamylated protein antibodies as a diagnostic marker in patients with rheumatoid arthritis and its association with disease activity

QJM ◽

10.1093/qjmed/hcab116.005 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Magda Medhat Awad El debsy ◽

Mervat Mohammed Abdul Hakim ◽

Henaz Farouk Khaled ◽

Hala Mohamed Abd El Sabour Sabbah

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Plasma Levels ◽

Significant Positive Correlation ◽

Diagnostic Marker ◽

Complete Blood Count ◽

Control Group ◽

Positive Correlation ◽

Larsen Score ◽

Function Tests

Abstract Background Despite the diagnostic contribution of anti-citrullinated protein( anti-CCP) antibody and rheumatoid factor (RF), approximately one-third of patients with rheumatoid arthritis (RA) remain seronegative .Anti-carbamylated protein (Anti-Carp) antibodies have been attracting increasing attention as a new diagnostic marker of RA. Objective evaluate levels of anti-carp antibodies in RA patients in order to detect its role as a diagnostic marker and its possible association with disease activity and severity. Methods This study included thirty adult patients with clinical evidence of rheumatoid arthritis and thirty healthy matched age and sex as controls. All underwent history taking, clinical examination, assessment of disease activity with modified Disease Activity28 (DAS28), Laboratory investigations including Complete blood count (CBC), erythrocytes sedimentation rate (ESR), C-Reactive Protein (CRP), Liver function tests, Kidney function tests, Serum uric acid, RF, anti CCP Ab, anti-Carp Ab and radiographic Assessment with Larsen score. Results Plasma levels of anti-Carp Ab were significantly higher in patients than control group (p > 0,001) with sensitivity of 73.33% and specificity of 100%.it showed significant positive correlation with CRP (r = 0.37 )(p < 0.05) as a marker of activity of RA and also there was significant positive correlation with RF and ACPA (r = 0.45)(r = 0.48) (p < 0.05) respectively as a diagnostic marker for RA. Plasma levels of anti-Carp Ab were higher in patients with more joints damage and erosions as assessed by Larsen radiological score as there was a highly significant correlation between Larsen score and serum Anti-Carp(r = 0.61)(p < 0.001).. Conclusion serum Anti–Carp antibody level was higher in RA patients which serve as a diagnostic marker for RA, also its significant correlation with CRP and Larsen score may serve as a marker for disease progression and severity.

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Association of Vitamin D Status with Semen Parameters and Male Reproductive Hormones in Egyptian Infertile Men

Austin Andrology ◽

10.26420/austinandrology.2021.1028 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Doaa Abou-Taleb AE ◽

◽

Mahran AM ◽

Mahmoud MA ◽

Gaber MA ◽

...

Keyword(s):

Vitamin D ◽

Significant Positive Correlation ◽

Reproductive Hormones ◽

Male Reproduction ◽

Semen Parameters ◽

Unknown Etiology ◽

Control Group ◽

Positive Correlation ◽

Infertile Men

Background: Although vitamin D receptor (VDR) is expressed in human sperm, little is known about the role of vitamin D (Vit. D) in male reproduction. Our objective was to assess Vit. D levels both in serum and seminal fluid and to establish the relation between serum and seminal Vit. D levels, semen parameters, male sex hormones and serum calcium level in Egyptian infertile men. Patients and Methods: We conducted a prospective case control study including 30 healthy fertile males as a control group and 60 male patients with infertility of unknown etiology. Semen samples were collected and semen parameters were evaluated. Also, seminal Vit. D level was measured. Blood samples were taken as serum levels of Vit. D, calcium, testosterone, Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) were estimated. Results: There was significant decrease of both serum and seminal Vit. D level in groups of male infertility compared to control group. A significant positive correlation was found between serum and seminal Vit. D levels in different study groups. Also, significant positive correlation between serum Vit. D level and non-progressive sperm motility. Conclusion: Our results support the role of Vit. D in semen parameters and male fertility status.

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