Vitreous Cytokine Levels Research Articles

Optical coherence tomography biomarkers as outcome predictors to guide dexamethasone implant use in patients with iERM: a randomized controlled trial

BackgroundWe aimed to investigate the anatomical features of optical coherence tomography (OCT) and vitreous cytokine levels as predictors of outcomes of combined phacovitrectomy with intravitreal dexamethasone (DEX) implants for idiopathic epiretinal membrane (iERM) treatment.MethodsA prospective, single-masked, randomized, controlled clinical trial included 48 eyes. They were randomly assigned in a 1:1 ratio to undergo the DEX group (combined phacovitrectomy with ERM peeling and Ozurdex implantation) and control group (phacovitrectomy only). Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed at 1 d, 1 week, 1 month, and 3 months. The structural features of OCT before surgery were analysed for stratified analysis. Baseline soluble CD14 (sCD14) and sCD163 levels in the vitreous fluid were measured using ELISA.ResultsBCVA and CMT were not significantly different in the DEX and control groups. Eyes with hyperreflective foci (HRF) at baseline achieved better BCVA (Ptime*group=0.746; Pgroup=0.043, Wald χ²=7.869) and lower CMT (Ptime*group = 0.079; Pgroup = 0.001, Wald χ²=6.774) responses to DEX during follow-up. In all patients, the mean vitreous level of sCD163 in eyes with HRF was significantly higher than that in eyes without HRF (P = 0.036, Z=-2.093) at baseline. In the DEX group, higher sCD163 predicted greater reduction in CMT from baseline to 1 month (r = 0.470, P = 0.049).ConclusionsWe found that intraoperative DEX implantation did not have beneficial effects on BCVA and CMT over a 3-month period in all patients with iERM, implying that the use of DEX for all iERM is not recommended. In contrast, for those with HRF on OCT responded better to DEX implants at the 3-month follow-up and thier vitreous fluid expressed higher levels of sCD163 at baseline. These data support the hypothesis that DEX implants may be particularly effective in treating cases where ERM is secondary to inflammation.Trial registrationThe trail has been registered at Chinese Clinical Trail Registry(https://www.chictr.org.cn) on 2021/03/12 (ChiCTR2100044228). And all patients in the article were enrolled after registration.

Investigating Vitreous Cytokines in Choroidal Melanoma.

Due to the close relationship between the vitreous and posterior eye layers, the microenvironment of these layers can affect the composition of the vitreous. Molecular analysis of the vitreous may therefore provide important insights into the pathogenesis of chorioretinal diseases. In this study, vitreous cytokines (n = 41) were evaluated to gain further insights into the tumor microenvironment in uveal melanoma (UM) arising from the choroid (CM). Cytokine levels were measured using a bead-based multiplex immunoassay panel in vitreous samples obtained from 32 eyes, including 18 with CM and 14 controls. Median fluorescence intensity values were extracted and used as relative quantification of the cytokine abundance. Vitreous cytokine levels were compared between the CM and non-CM groups and between different prognostic categories within the CM group (classified as having low or high metastatic risk using tumor biopsy-based gene expression profiling). Correlations between vitreous cytokine levels and tumor dimensions were also evaluated. Our analysis revealed twenty-six vitreous cytokines significantly upregulated in CM-affected eyes compared to the control eyes. Within the CM group, six vitreous cytokines showed altered levels (five upregulated and one downregulated) in eyes with high- vs. low-risk tumors. Levels of these six plus several other cytokines showed correlations with the tumor dimensions. In conclusion, our study has uncovered several UM-relevant vitreous cytokines, worthy of follow-up in larger studies as potential candidates for liquid biopsy-based biomarker development and/or new therapeutic targeting.

Vitreous cytokine levels following the administration of a single 0.19 mg fluocinolone acetonide (ILUVIEN®) implant in patients with refractory diabetic macular edema (DME)—results from the ILUVIT study

PurposeTo investigate the changes in vitreous inflammatory and angiogenic cytokine levels, primarily interleukin-(IL)-6, following intravitreal injection of the 0.19 mg fluocinolone acetonide (FAc, ILUVIEN®) implant in patients with diabetic macular edema.MethodsA single-center phase IV study involving 12 patients’ eyes with diabetic macular edema. Vitreous fluid samples were obtained prior to intravitreal injection of the fluocinolone acetonide implant and then again over a 6-month period. Vitreous samples were examined using a cytometric bead array to measure IL-6, IL-8, IP-10, MCP-1, VEGF, and CD54. PIGF and PEDF were measured using an enzyme-linked immunosorbent assay. Changes in the cytokine and chemokine expression patterns were analyzed. Clinical parameters such as BCVA and center point thickness (CPT) were also examined.ResultsThere were mean reductions in all parameters between baseline and month 6. Significant changes (p < 0.05 versus baseline) were observed in the expression of IL-6, IP-10, MCP-1, and CD54 following the administration of fluocinolone acetonide implant. VEGF and PIGF increased at month 1 before declining at month 6, though this trend was not significant. CPT decreased rapidly between screening and the first follow-up visit, and this decrease was sustained. BCVA remained relatively stable throughout.ConclusionThis study demonstrated changes in vitreous inflammatory and angiogenic cytokine levels following intravitreal injection of the FAc implant in patients with diabetic macular edema. Data show that the fluocinolone acetonide implant led to rapid and sustained reductions of some inflammatory cytokines with improvement of the overall clinical picture.

Changes of vitreous cytokine levels in eyes with PDR after intravitreal injection of Ranibizumab or Triamcinolone acetonide

Changes of vitreous cytokine levels in eyes with PDR after intravitreal injection of Ranibizumab or Triamcinolone acetonide

Association between aqueous humor and vitreous fluid levels of Th17 cell-related cytokines in patients with proliferative diabetic retinopathy.

Inflammation is known to be involved in the progression of diabetic retinopathy. We have recently reported that vitreous levels of IL-4, IL-17A, IL-22, IL-31, and TNFα are higher than the respective serum levels in proliferative diabetic retinopathy (PDR) patients, and that vitreous levels of these cytokines are higher in PDR than in other non-inflammatory vitreoretinal diseases or uveitis associated with sarcoidosis. In the present study, we investigated inflammatory cytokines including Th17 cell-related cytokines in aqueous humor samples obtained from eyes with PDR, and analyzed the association between the aqueous humor and vitreous fluid levels of individual cytokines. The study group consisted of 31 consecutive type 2 diabetic patients with PDR who underwent cataract surgery and vitrectomy for vitreous hemorrhage and/or tractional retinal detachment. Undiluted aqueous humor was collected during cataract surgery, and then vitreous fluid was obtained using a 25G vitreous cutter inserted into the mid-vitreous cavity at the beginning of vitrectomy. IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, soluble CD40 ligand (sCD40L), and TNFα levels in the aqueous humor and vitreous fluid were measured using a beads-array system. Although IL-17A was detected in the aqueous humor of eyes with PDR and the level correlated with IL-17A level in the vitreous fluid, both percent detectable and level of IL-17A in the aqueous humor were significantly lower than those in the vitreous fluid. Vitreous IL-17A level was related significantly to IL-10, IL-22, and TNFα levels in aqueous humor as well as in vitreous fluid, On the other hand, aqueous IL-17A level was not related significantly to aqueous or vitreous levels of IL-10, IL-22 or TNFα level. The present study demonstrated that IL-17A level and detectable rate in the aqueous humor of patients with PDR are markedly lower than those in the vitreous fluid and aqueous IL-17A does not correlate with vitreous levels of other cytokines, and hence should not be used as a surrogate for IL-17A in the vitreous fluid.

Efficiency of Ozone Therapy in a Rat Model of Experimental Uveitis

ABSTRACTPurpose: To investigate efficiency of ozone therapy in uveitis.Methods: A total of 24 albino Wistar rats were randomly assigned to four groups (n = 6); (a) control group; (b) sham group; (c) infliximab treatment group; (d) ozone therapy group. Vitreous haze scores of all groups were evaluated. Vitreous cytokine levels (TNF-α, IL-1, IL-6) measured by ELISA and eyes were enucleated for histopathologic examination.Results: According to vitreous haze scores, there was statistically significant inflammation in Group (b) compared with Group (a), and there was less inflammation in infliximab and ozone groups compared with Group (b) (p < 0.05). Cytokine levels in infliximab and ozone groups were lower but not statistically significant when compared with Group (b) (p > 0.05). There was significantly less inflammation in histopathologic examination in treatment groups when compared with the sham group (p < 0.05).Conclusions: Clinical and histopathologic examination results indicate that systemic application of ozone may be efficient in the treatment of uveitis.

The comparison of the impact of ghrelin and tacrolimus on vitreous cytokine levels in an experimental uveitis model

We aimed to compare the effects of intraperitoneal ghrelin and tacrolimus on vitreous levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6) in an experimental autoimmune uveitis model. Twenty-four male rats, each weighing 300 g, were assigned into four groups, six rats in each. All the rats, except for those in group 1, were injected intravitreally with concanavalin a to induce experimental uveitis. The development of uveitis was confirmed by the histopathologic examination of two rat globes from each group. The rats in group 2 were not given any treatment after uveitis was induced. The rats in group 3 were administered 1 mg/kg/day of intraperitoneal tacrolimus on days 0, 1, 3, 5 and 7 following the induction of uveitis (on the 14th day of study). The rats in group 4 were given 10 ng/kg/day of intraperitoneal ghrelin for 7 days following the induction of uveitis. On the 21st day of the study, all rats were sacrificed, and the eyes enucleated were subjected to histopathologic examination. Vitreous levels of TNF-α, IL-1 and IL-6 were measured by the enzyme-linked immunosorbent assay method. The histopathologic evaluation carried out to confirm the development of uveitis revealed destruction in the retinae and ciliary bodies of the immunized rats. The mean vitreous levels of TNF-α, IL-1 and IL-6 were significantly higher in the sham group than in the control group (p < 0.05). The levels of these three cytokines showed a significant decrease in the tacrolimus treatment group (p < 0.05). Cytokine levels decreased in the ghrelin treatment group relative to the control group; however, the decrease was not found statistically significant (p > 0.05). Tacrolimus could be effective in uveitis treatment by neutralizing or decreasing the levels of cytokines such as TNF-α, IL-1 and IL-6 that have a critical part in the pathogenesis of uveitis. However, ghrelin failed to produce the desired effect. Further studies using different doses and different ways of administration are needed to determine the effective dose of ghrelin in uveitis.

Impact of ghrelin on vitreous cytokine levels in an experimental uveitis model

BackgroundThe purpose of this study was to investigate the effect of intraperitoneal ghrelin on vitreous levels of interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-α) and to compare its effects with those of intraperitoneal infliximab in an experimental uveitis model.MethodsTwenty-four male rats were assigned to four groups of six rats in each. All the rats, except for those in group 1 (controls), were injected intravitreally with concanavalin A to induce experimental uveitis. Rats in group 2 (sham) were not given any treatment after uveitis was induced. Rats in group 3 were given intraperitoneal infliximab 0.5 mg/100 mL on days 0, 1, 3, 5, and 7 following induction of uveitis on day 14 of the study. Rats in group 4 were given intraperitoneal ghrelin 10 ng/kg/day for 7 days following induction of uveitis. On day 21 of the study, enucleated globes were subjected to histopathologic examination. Vitreous levels of IL-1, IL-6, and TNF-α were measured by enzyme-linked immunosorbent assay.ResultsVitreous levels of IL-1, IL-6, and TNF-α were significantly increased in the sham group relative to the control group (P < 0.05), but showed a significant decrease in the group treated with infliximab (P < 0.05). Cytokine levels also decreased in the ghrelin-treated group, but the decrease was not statistically significant (P > 0.05).ConclusionGhrelin failed to decrease the IL-1, IL-6, and TNF-α levels that play a critical role in the pathogenesis of uveitis.

INCREASES OF VITREOUS MONOCYTE CHEMOTACTIC PROTEIN 1 AND INTERLEUKIN 8 LEVELS IN PATIENTS WITH CONCURRENT HYPERTENSION AND DIABETIC RETINOPATHY

To investigate whether concurrent hypertension affects vitreous cytokine levels in diabetic retinopathy. Vitreous samples from 41 patients with diabetic retinopathy with or without concurrent hypertension, who underwent vitrectomy, were collected. Vitreous cytokine concentrations were simultaneously measured using flow cytometry. Patients were stratified according to hypertension or other clinical conditions, and the differences in vitreous levels of monocyte chemotactic protein 1, interleukin 8, vascular endothelial growth factor, interferon-inducible protein 10, and monokine induced by interferon gamma were examined. Vitreous levels of monocyte chemotactic protein 1 and interleukin 8 were significantly (P < 0.05) higher in hypertensive patients than in nonhypertensive patients and were significantly (P < 0.05) higher in active diabetic retinopathy than in inactive diabetic retinopathy. Vitreous levels of vascular endothelial growth factor, interferon-inducible protein 10, and monokine induced by interferon gamma were not affected by the coexistence of hypertension. In multivariate models, active diabetic retinopathy (P = 0.004 and P = 0.007), systolic blood pressure (P = 0.039 and P = 0.041), and hypertension (P = 0.032 and P = 0.035) were significant and independent predictors for increased vitreous monocyte chemotactic protein 1 and interleukin 8 levels. Both monocyte chemotactic protein 1 and interleukin 8 levels were elevated in the vitreous of patients with diabetic retinopathy and concurrent hypertension. These findings may help to explain the epidemiologic and clinical evidence that systemic hypertension exacerbates diabetic retinopathy.

Panretinal photocoagulation induces pro-inflammatory cytokines and macular thickening in high-risk proliferative diabetic retinopathy

To investigate whether pan-retinal photocoagulation (PRP) affects vitreous levels of cytokines and macular thickening in patients with high-risk proliferative diabetic retinopathy (PDR). Fourteen patients with bilateral high-risk PDR--which requires pars plana vitrectomy (PPV)--but without a history of retinal photocoagulation participated in this study. Before PPV, one eye received PRP, and the other eye did not. The concentrations of cytokines of vascular endothelial growth factor (VEGF), stromal derived factor-1 (SDF-1), interleukin-6 (IL-6) and regulated upon activation, normal T-cell expressed and secreted (RANTES) were measured in each vitreous sample obtained at PPV. Macular thickness obtained by optical coherence tomography was also monitored during clinical course. After the PRP, macular thickness in PRP-pretreated eye showed temporal increase. Vitreous levels of IL-6 and RANTES in PRP pre-treated eye were significantly higher than levels in control eyes (p = 0.013, p = 0.033). Although macular thickness in control was correlated to vitreous levels of VEGF and IL-6 (p = 0.022, p = 0.003), that in PRP-pretreated eye was closely correlated to IL-6 and RANTES (p = 0.002, p = 0.011). After the PPV, macular thickness in both eye groups improved, and there was no significant difference between both eye groups 3 months after the PPV. In patients with high-risk PDR, PRP cause temporal worsening of macular edema linked with pro-inflammatory cytokines of IL-6 and RANTES, but not with VEGF and SDF-1. Thus, PRP-induced macular edema was caused by inflammation, while visual prognosis after PPV was not influenced by pretreatment of PRP.

Visual prognosis and vitreous cytokine levels after arteriovenous sheathotomy in branch retinal vein occlusion associated with macular oedema

To investigate the relationship between vitreous levels of cytokines, including interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF), and visual prognosis after pars plana vitrectomy (PPV) with arteriovenous sheathotomy in patients with branch retinal vein occlusion (BRVO) associated with macular oedema. We studied 60 patients with logMAR visual acuity (VA) scores of < 0.3 and visual impairment secondary to BRVO-associated macular oedema. All patients underwent PPV with arteriovenous sheathotomy. At the time of PPV, vitreous samples were collected from the operated eye and vitreous levels of VEGF and IL-6 were measured. Best corrected VA (BCVA) (using a logMAR chart) and foveal thickness (FT) (using optical coherence tomography) were monitored for up to 6 months after PPV. Both BCVA and FT significantly improved after PPV. According to multiple regression analysis, both the improvement in BCVA and decrease in FT were closely related to the vitreous level of IL-6 but not to that of VEGF. The vitreous level of VEGF was strongly correlated with duration of BRVO. Both improvement in BCVA and decrease in FT were observed after PPV in BRVO patients with macular oedema. Interestingly, these visual prognoses strongly correlate with the vitreous level of IL-6, whereas the duration of BRVO strongly correlates with the vitreous level of VEGF.

Risk evaluation of outcome of vitreous surgery based on vitreous levels of cytokines

To ascertain whether vitreous and plasma levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) and fundus findings could predict the outcome of vitreous surgery in patients with proliferative diabetic retinopathy (PDR). Vitreous fluid samples were obtained during vitreoretinal surgery from 73 consecutive eyes with PDR. The levels of VEGF and IL-6 in vitreous fluid and plasma were determined by enzyme-linked immunosorbent assay. Patients were prospectively followed for 6 months and the postoperative outcome was analysed by logistic regression analysis. No improvement and/or progression of PDR occurred in 23 (32%) of the 73 eyes (progression group). The vitreous levels of VEGF and IL-6 were significantly higher in eyes from the progression group than in eyes with regression of PDR (regression group) (P=0.0032 and 0.0088, respectively). Multivariate logistic regression analysis showed that higher vitreous levels of VEGF were associated with the progression of PDR after vitreous surgery (odds ratio 2.72, P=0.0003). High vitreous levels of VEGF identified as a significant risk factor for the outcome of vitreous surgery in patients with PDR. A model was developed to predict the probability of PDR progression and measurement of the vitreous level of VEGF may be useful for predicting the outcome of surgery.

The effect of infliximab, cyclosporine A and recombinant IL-10 on vitreous cytokine levels in experimental autoimmune uveitis

To identify the effect of infliximab, cyclosporine A and recombinant IL-10 in experimental autoimmune uveitis. Sixty male rats were assigned to five groups of 12 each. All the groups (except the control group) were administered 30 microg retinal-S antigen intraperitoneally. On the 14th day, after confirmation of uveitis with histopathological study, daily cyclosporine A injection was given in cyclosporine A treatment group and physiological serum in the uveitis-induced placebo treatment and control groups. In the infliximab treatment group, infliximab was administered on the 14th, 15th, 17th, 19th and 21st days. In the recombinant IL-10 treatment group, three doses of recombinant IL-10 were given four hours and a half hours before and eight hours after retinal-S antigen administration. On the 21st day of the study, all rats were sacrificed and vitreous cytokine levels (IL-1, IL-6, IL-8 and TNF-alpha) were studied with ELISA. In the treatment groups, cytokine levels (IL-1, IL-6 and TNF-alpha) were significantly lower than the uveitis-induced placebo treatment group. Compared with the control group, there was no significant difference with respect to TNF-alpha and IL-8 in the infliximab treatment group; IL-8 in the cyclosporine A treatment group; IL-6 and IL-8 in the recombinant IL-10 treatment group. The drugs used did not significantly differ in respect to their effects on vitreous IL-6, IL-8 and TNF-alpha levels. Cyclosporine A, infliximab and recombinant IL-10 reduce the vitreous cytokines levels. Among these drugs, recombinant IL-10, which is still in its experimental phase, might be considered as a new therapeutic agent.