Guideline for the treatment of no light perception eyes induced by mechanical ocular trauma.

Severe mechanical ocular trauma with no light perception (NLP) predicts a poor prognosis of visual acuity and enucleation of the eyeball. Since the innovative treatment concept of exploratory vitreoretinal surgery has developed and treatment technology has advanced, the outcomes of severe ocular trauma treatment in NLP patients have greatly improved. However, there remains a lack of unified standards for the determination, surgical indication, and timing of vitrectomy in NLP eye treatment. To address these problems, we aimed to create evidence-based medical guidelines for the diagnosis, treatment, and prognosis of mechanical ocular trauma with NLP. Sixteen relevant recommendations for mechanical ocular trauma with NLP were obtained, and a consensus was reached. Each recommendation was explained in detail to guide the treatment of mechanical ocular trauma associated with NLP.

Excited State Dynamics of Methylated Guanosine Derivatives Revealed by Femtosecond Time-resolved Spectroscopy.

Methylated DNA/RNA nucleobases are important epigenetic marks in living species and play an important role for targeted therapies. Moreover, methylation could bring significant changes to the photo-stability of nucleic acid, leading these sites become mutational hotspots for disease such as skin cancer. While a number of studies have demonstrated the relationship between excited state dynamics and the biological function of methylated cytosine in DNA, investigations aimed at unraveling the excited state dynamics of methylated guanosine in RNA have been largely overlooked. In this work, influence of methylation on the excited state dynamics of guanosine is studied by using femtosecond time-resolved spectroscopy. Our results suggest that the effect of methyl substitution on the photophysical properties of guanosine is position sensitive. N1-methylguanosine shows very similar excited state dynamics as that in guanosine, while almost one order of magnitude longer lifetime of the La state is observed in N2, N2-dimethylguanosine. Notably, N7-methylation can lead to a new minimum on the La state and the excited state lifetime is two orders of magnitude longer than that of guanosine. These findings not only help understanding excited state dynamics of methylated guanosines, but also lay the foundation for further studying DNA/RNA strands incorporated with these bases.

Mechanism and prognostic indicators for explosion-related eye trauma: eye injury vitrectomy study.

PURPOSE: To explore the clinical features, surgical interventions and prognosis of injured eyes following explosion and to develop the risk factors for poor prognosis. METHODS: A nested case-control study. To the date of 31 December 2018, 99 explosion-related eye globes were selected from the Eye Injury Vitrectomy Study database, which is a multicenter prospective cohort study and began in 1990s. All cases selected underwent vitreoretinal surgery or enucleation and were followed up for at least 6 months. Clinically meaningful preoperative variables and outcomes were used to develop logistic regression models. RESULTS: The unfavourable outcomes were defined as silicone oil-filled eyes, phthisis bulbi, enucleation and anatomically restored eyes whose final BCVA is worse than initial vision after 6 months of follow-up. The proportion of unfavourable outcomes was 92.0%, 60.9% and 66.7% in large festive fireworks, detonator and beer bottle groups respective. The anatomic and visual outcome of injured eyes with combined injury of blast wave and projectile were worse than that of ruptured eyes (Fisher's exact = 0.041). The extrusion of iris/lens (OR = 3.20, p = 0.015), PVR-C (OR = 6.08, p = 0.036) and choroid damage (OR = 5.84, p = 0.025) is independent risk factors of unfavourable prognosis for explosion-related eye trauma. CONCLUSION: The extrusion of iris/lens, PVR-C and choroid damage is the independent risk factors for unfavourable outcomes in explosion-related eye trauma. There is a unique injury mechanism in explosion-related eye trauma. SUMMARY STATEMENT: Through the nested case-control study, the extrusion of iris/lens, PVR-C, and choroid damage are the independent risk factors for unfavorable outcomes in explosion-related eye trauma. The mechanism of open globe mixture and close globe mixture in explosion-related eye trauma need more cases and participating units to explore together in the future.

Long-term follow-up of primary silicone oil tamponade for retinal detachment secondary to macular hole in highly myopic eyes: a prognostic factor analysis.

PURPOSE: To investigate the risk factors associated with retinal detachment recurrence after first vitrectomy in high myopic eyes with macular hole retinal detachment (MHRD). METHODS: Patients with high myopic eyes with MHRD who underwent pars plana vitrectomy and silicone oil (SO) tamponade with a follow-up period more than 12 months and more than 3 months after SO removal were included in this retrospective study. Logistic regression was performed to determine the risk factors associated with retinal re-detachment. RESULTS: A total of 45 eyes from 43 patients were included in this study (11 male and 34 female patients). The retinal re-detachment rate after the first removal of silicon oil was 35.5% (16/45) in a mean postoperative follow-up time of 35.64 ± 32.94 months. Complete macular atrophy on fundus photography (odds ratio (OR) = 17.021, 95% confidence interval (95% CI): 2.218-130.609, p = 0.006) was a risk factor for MHRD after SO removal, while internal limiting membrane (ILM) peeling (OR = 0.091, 95% CI: 0.013-0.633, p = 0.015) and duration of SO tamponade (OR = 0.667, 95% CI: 0.454-0.980, p = 0.039) were protective factors. CONCLUSION: For high myopic eyes with MHRD, complete macular atrophy was a significant risk factor for retinal re-detachment after silicon oil removal. ILM peeling and the duration of silicon oil tamponade were protective factors.

Tangeretin Inhibition of High-Glucose-Induced IL-1ß, IL-6, TGF-ß1, and VEGF Expression in Human RPE Cells.

Tangeretin, a natural compound extracted from citrus plants, has been reported to have antiproliferative, antidiabetic, anti-invasive, and antioxidant properties. However, the role of tangeretin in diabetic retinopathy (DR) is unknown. In the present study, we investigated whether tangeretin had any effect on the expression of interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), transforming growth factor beta 1 (TGF-ß1), and vascular endothelial growth factor (VEGF) in human retinal pigment epithelial (RPE) cells under high-glucose (HG) conditions. Our results illustrated that HG levels induced IL-1ß, IL-6, TGF-ß1, and VEGF expression and that tangeretin significantly reduced HG-induced IL-1ß, IL-6, TGF-ß1, and VEGF expression in human RPE cells. Moreover, tangeretin efficiently inhibited the activation of the protein kinase B (Akt) signalling pathway in HG-stimulated RPE cells. Therefore, tangeretin may serve a role in the treatment of DR.

Effect of macrophage migration inhibitory factor on inflammatory cytokines and fibrogenic gene expression in human RPE cells.

Proliferative vitreoretinopathy (PVR) is a vision­threatening disease. It is also a common complication resulting from surgery to correct rhegmatogenous retinal detachment. Proliferation and migration of retinal pigment epithelial (RPE) cells and the secretion of extracellular matrix molecules play an important role in the formation of the preretinal membrane in PVR patients. Furthermore, upregulated expression of inflammatory cytokines within the vitreous or subretinal fluid of patients experiencing vitreoretinal disorders may aggravate the inflammatory response and be involved in the development of PVR. PVR is triggered by many inflammatory cytokines and growth factors. Macrophage migration inhibitory factor (MIF), an inflammatory cytokine, is upregulated in the vitreous in PVR patients. However, there is little known concerning the connection between MIF and the expression of inflammatory cytokines, interleukin­6 (IL­6) and monocyte chemotactic­1 (MCP­1), and the fibrogenic gene, collagen I, in human RPE cells. Cell proliferation, migration, and expression of IL­6, MCP­1 and collagen I were assessed using an MTT assay, a Transwell assay, real­time PCR analysis and ELISA kits. Western­blot analysis was used to detect phosphorylation of p38 mitogen activated protein kinase (MAPK) and extracellular signal­regulated kinase (ERK) signaling pathways. The data revealed that MIF promoted the proliferation, migration and expression of IL­6, MCP­1 and collagen I, and phosphorylation of p38 and ERK signaling pathways in RPE cells in vitro. These findings suggest that MIF plays a proinflammatory and profibrotic role in the development of PVR.

Preoperative Timing of Intravitreal Bevacizumab Injection for Proliferative Diabetic Retinopathy Patients.

OBJECTIVE: To evaluate the changes in aqueous concentrations of inflammatory cytokines and fibrosis-related factors, and to detect the expression of vascular endothelial growth factor (VEGF) and proliferating cells in fibrovascular membranes (FVMs) of patients with proliferative diabetic retinopathy (PDR) after injection of intravitreal bevacizumab (IVB). METHODS: Forty-two eyes of 42 patients with PDR, including 28 eyes that received IVB (1.25 mg) 2, 5, and 14 days before pars plana vitrectomy (PPV), and 14 eyes without IVB, were enrolled, in addition to 10 eyes of 10 patients with nondiabetic ocular diseases. Aqueous concentrations of inflammatory cytokines and fibrosis-related factors were analyzed by a multiplex bead assay. Fluorescence immunostaining was performed to examine the expression of VEGF and proliferating cells in the excised epiretinal membranes. RESULTS: PDR eyes without IVB had the highest vitreous VEGF levels, and the level was statistically significant compared with that of PDR eyes that received IVB 2 days before surgery, PDR eyes that received IVB 5 days before surgery, and nondiabetic eyes (p = 0.011, p = 0.012, and p < 0.001, respectively). The expression of fibroblastic cells and connective tissue growth factor increased in epiretinal FVMs of the IVB group 21 days after treatment. CONCLUSIONS: IVB injection may lead to a decrease in the intraocular concentrations of VEGF after 2-5 days and induce the formation of proliferation after 21 days, which suggests that PPV in PDR patients should take place within 1 week of the administration of preoperative IVB.

Apelin-13 Is an Early Promoter of Cytoskeleton and Tight Junction in Diabetic Macular Edema via PI-3K/Akt and MAPK/Erk Signaling Pathways.

Diabetic macular edema is major cause of vision loss associated with diabetic retinopathy. Breakdown of blood-retinal barrier, especially inner BRB, is an early event in pathogenesis of DR. Apelin, an endogenous ligand of APJ, mediates angiogenesis and is involved in the development of DR. The present study aimed to investigate effects and mechanism of apelin-13 in vascular permeability during DME. We verified apelin-13 was upregulated in DME patients' vitreous. High glucose incubation led to a progressive increase of apelin-13, APJ, cytoskeleton, and tight junction proteins, including VE-Cadherin, FAK, Src, ZO-1, and occludin. Apelin-13 promoted HRMEC proliferation and migration and phosphorylation of both cytoskeleton and tight junction under both normal and high glucose conditions. Besides, apelin-13 activated PI-3K/Akt and MAPK/Erk signaling pathways, including PLCγ1, p38, Akt, and Erk both in HRMEC and in C57BL/6 mice. Meanwhile, F13A performed opposite effects compared with apelin-13. In in vivo study, apelin-13 was also upregulated in retina of db/db mice. Taken together, apelin-13 increased biologic activity of HRMEC, as well as expression of both cytoskeleton and tight junction in DME via PI-3K/Akt and MAPK/Erk signaling pathways. Apelin-13 as an early promoter of vascular permeability may offer a new perspective strategy in early treatment of DR.

Differences in aqueous concentrations of cytokines in paediatric and adult patients with Coats' disease.

PURPOSE: To investigate the differential aqueous concentrations of vascular endothelia growth factor (VEGF) and inflammatory cytokines in paediatric and adult patients with Coats' disease. METHODS: A total of 20 eyes of 20 patients with Coats' disease, 12 eyes of 12 paediatric patients, and eight eyes of eight adult patients, six patients (six eyes) with congenital cataract as the paediatric control group and 10 patients (10 eyes) with senile cataract as the adult control group were examined. Aqueous humour samples were assessed for interleukin-6, -8, -1ß (IL-6, IL-8, IL-1ß, respectively), basic fibroblast growth factor, monocyte chemo-attractant protein 1, tumour necrosis factor alpha and VEGF by multiplex bead assay. RESULTS: Significantly, higher concentrations of VEGF, IL-6 and IL-1ß were found in the paediatric patients with Coats' disease (p = 0.001, p = 0.004 and p = 0.006). Concentration of VEGF in the paediatric patients with Stage 3B of Coats' disease was significantly higher than that of Stage 3A (p = 0.010). In the adult patients with Coats' disease, the aqueous levels of IL-6 and IL-1ß were significantly higher than that of the controls (p = 0.012, and p = 0.005). The concentration of IL-6 was significantly linearly associated with the extent of exudative retinal detachment (p = 0.003, R = 0.892). CONCLUSIONS: Increasing severity of Coats' disease is significantly associated with intraocular VEGF concentration in the paediatric patients. And IL-6 may be involved with the inflammatory process in the adult patients with Coats' disease.

The relationship between anti-vascular endothelial growth factor and fibrosis in proliferative retinopathy: clinical and laboratory evidence.

PURPOSE: To investigate the progression of epiretinal membranes after intravitreal bevacizumab (IVB) injection therapy in patients with proliferative membranes and evaluate the changes in fibrosis-related cytokines in retinal pigment epithelial cells and glial cells after treatment with bevacizumab. METHODS: Retrospective study of the proliferative membranes in patients with and without IVB therapy. In vitro, the human adult retinal pigment epithelial (ARPE-19) cells and BV2 microglial cell lines were incubated in different bevacizumab concentrations under hypoxic conditions. Cell culture supernatants and cell lysates were harvested after incubation for 24, 48 or 72 hours for ELISA and western blot. RESULTS: Bevacizumab accelerated fibrosis in patients with proliferative membranes. Immunofluorescence analysis revealed more intense transforming growth factor ß2 (TGFß2) and connective tissue growth factor (CTGF) staining in IVB-treated proliferative diabetic retinopathy (PDR) membranes compared with membranes of patients not receiving IVB therapy. This result was consistent with real-time PCR results. Bevacizumab incubation significantly upregulated TGFß2 and CTGF in ARPE-19 cells and BV2 microglial cells, but ciliary neurotrophic factor (CNTF) expression was upregulated only in BV2 microglial cells. CONCLUSIONS: Anti-vascular endothelial growth factor treatment likely accelerates fibrosis in PDR patients via upregulation of TGFß2, CTGF and CNTF, suggesting the importance of adjunctive therapy for retinal fibrosis.

TLR4 inhibitor attenuates amyloid-ß-induced angiogenic and inflammatory factors in ARPE-19 cells: Implications for age-related macular degeneration.

Subretinally-deposited amyloid-ß (Aß) is an important factor in age­related macular degradation (AMD) often leading to irreversible blindness in the elderly population. The molecular mechanism underlying Aß deposition during AMD remains unclear. The expression of inflammatory and angiogenic factors was examined by treatment of retinal pigment epithelial (RPE) cells with the oligomeric form of Aß (OAß1-42). Changes in the mRNA expression levels of various cytokines was detected by the QuantiGenePlex 6.0 Reagent system, and the protein expression level was determined by western blotting. Culture supernatants were detected using a multiplex cytokine assay and enzyme-linked immunosorbent assays. The in vitro tube formation was evaluated by a Matrigel assay. The present study highlights that OAß1­42 activates the toll-like receptor 4 (TLR4), myeloid differentiation factor 88 and phosphorylation nuclear factor-κB signaling pathway in RPE cells. Additionally, it increased the mRNA and protein expression of interleukin (IL)-6, IL-8, IL-33, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and angiopoietin 2. Furthermore, the TLR4 inhibitor (COBRA) attenuated the expression of inflammatory and angiogenesis factors, particularly IL-6, IL-8, IL-33, bFGF and VEGF. When human umbilical vein endothelial cells (HUVECs) were co-cultured with the COBRA-treated RPE cell culture supernatant the length of the endothelial cell network (measured by calculating tip cell lengths of endothelial cells) was impaired when compared with the HUVECs that were co­cultured with the cell supernatant exposed to OAß1­42. These results suggest that the TLR4-associated pathway may be a potential target for the treatment of AMD.

A new method to predict anatomical outcome after idiopathic macular hole surgery.

PURPOSE: To investigate whether a new macular hole closure index (MHCI) could predict anatomic outcome of macular hole surgery. METHODS: A vitrectomy with internal limiting membrane peeling, air-fluid exchange, and gas tamponade were performed on all patients. The postoperative anatomic status of the macular hole was defined by spectral-domain OCT. MHCI was calculated as (M+N)/BASE based on the preoperative OCT status. M and N were the curve lengths of the detached photoreceptor arms, and BASE was the length of the retinal pigment epithelial layer (RPE layer) detaching from the photoreceptors. Postoperative anatomical outcomes were divided into three grades: A (bridge-like closure), B (good closure), and C (poor closure or no closure). Correlation analysis was performed between anatomical outcomes and MHCI. Receiver operating characteristic (ROC) curves were derived for MHCI, indicating good model discrimination. ROC curves were also assessed by the area under the curve, and cut-offs were calculated. Other predictive parameters reported previously, which included the MH minimum, the MH height, the macular hole index (MHI), the diameter hole index (DHI), and the tractional hole index (THI) had been compared as well. RESULTS: MHCI correlated significantly with postoperative anatomical outcomes (r = 0.543, p = 0.000), but other predictive parameters did not. The areas under the curves indicated that MHCI could be used as an effective predictor of anatomical outcome. Cut-off values of 0.7 and 1.0 were obtained for MHCI from ROC curve analysis. MHCI demonstrated a better predictive effect than other parameters, both in the correlation analysis and ROC analysis. CONCLUSIONS: MHCI could be an easily measured and accurate predictive index for postoperative anatomical outcomes.

Vascular endothelial growth factor plasma levels before and after treatment of retinopathy of prematurity with ranibizumab.

PURPOSE: To evaluate vascular endothelial growth factor (VEGF) plasma levels before and after intravitreal injection of ranibizumab in patients with retinopathy of prematurity (ROP). METHODS: Case series study. Eleven infants with type 1 pre-threshold ROP were treated with intravitreal ranibizumab 0.5 mg. Blood samples were collected before intravitreal injection of ranibizumab and 1 day, 1 week, 2 weeks, and 4 weeks after injection. Concentration of plasma VEGF was measured by enzyme-linked immunosorbent assays (ELISA). RESULTS: The mean ± standard deviation of plasma VEGF concentration of the available samples before and 1 day, 1 week, 2 weeks, and 4 weeks after a total of 0.5 mg ranibizumab injection were 46.07 ± 9.40 pg/ml (n = 11), 10.59 ± 7.32 pg/ml (n = 5), 45.76 ± 6.75 pg/ml (n = 5), 62.44 ± 15.51 pg/ml (n = 5), and 56.82 ± 12.78 pg/ml (n = 4) respectively. A significant reduction was found in the plasma VEGF levels 1 day after intravitreal injection of ranibizumab (P = 0.002). No significant differences were found between before and 1 week, 2 weeks, and 4 weeks after the injection. CONCLUSIONS: Intravitreal ranibizumab reduced plasma VEGF levels 1 day after injection in infants with ROP. This effect disappeared 1 week after the injection. Intravitreal ranibizumab did not induce prolonged systemic VEGF suppression.

Effects of Apelin on RAW264.7 cells under both normal and hypoxic conditions.

Macrophages are an important source of pro-inflammatory and pro-angiogenic factors, which can promote pathological processes involving inflammation and angiogenesis. This study investigated the effects of Apelin on macrophages under both normal and hypoxic conditions. Under normal culture conditions, Apelin down-regulated the mRNA expression levels of monocyte chemotactic protein 1 (MCP1), monocyte chemotactic protein 3 (MCP3), macrophage inflammatory protein 1 (MIP1α, MIP1ß), vascular endothelial growth factor A (VEGFA), Angiopoietin 2 (Ang2) and tumor necrosis factor α (TNFα). The supernatant concentrations of MCP1, MCP3, MIP1α, MIP1ß, macrophage inflammatory protein 2 (MIP2) and TNFα proteins were significantly decreased in the Apelin treated group. Hypoxia induced profound up-regulations of the angiogenic, chemokine, and inflammatory factors at both the mRNA and protein levels. Apelin suppressed the hypoxia-induced increases in MCP1, MCP3, MIP2, MIP1ß and TNFα expression. The underlying mechanism of Apelin inhibit inflammation is regulating NF-κB/JNK signal pathway. Additionally, Apelin can protect macrophages from apoptosis and can enhance cell migration during hypoxia. And cleaved Caspase9/3 pathways were involved in Apelin inhibiting RAW264.7 apoptosis. In conclusion, we showed the effect of Apelin on RAW264.7 macrophage under normal and hypoxic condition, which could further influence the angiogenesis and inflammation process that promoted by macrophages.

Apelin activates the expression of inflammatory cytokines in microglial BV2 cells via PI-3K/Akt and MEK/Erk pathways.

This paper aims to observe the changes of the inflammatory cytokines in microglial BV2 cells stimulated by apelin, and investigate the mechanism of inflammatory cytokines secretion after apelin stimulation. Immunofluorescence and quantitative real-time PCR were performed to observe expression of TNF-α, IL-1ß, IL-10, MIP-1α, and MCP-1 in BV2 cells. Western blot was used to investigate the expression of phosphorylation PI-3K/Akt and phosphorylation Erk signaling pathways in BV2 cells after stimulation by apelin. Furthermore, PI-3K/Akt inhibitor (LY294402) and Erk inhibitor (U0126) were used as antagonists to detect the secretion mechanisms of cytokines in BV2 cells stimulated by apelin. Exogenous recombinant apelin activated the expression of TNF-α, IL-1ß, MCP-1 and MIP-1α in BV2 cells by the detection of fluorescence expression and mRNA. Apelin also unregulated the protein expression of p-PI-3K/Akt and p-Erk in BV2 cells induced by apelin. LY294002 and U0126 inhibited activation of p-PI-3K/Akt and p-Erk expression by Western blot and attenuated the expression of inflammation factors in BV2 cells by fluorescence staining. This study demonstrates that apelin is a potential activator of inflammation factors through the PI3K/Akt and Erk signaling pathway and is potential therapeutically relevant to inflammatory responses of microglia cells.

Clinical features and prognosis of eyeball rupture: eye injury vitrectomy study.

BACKGROUND: The objective of the study was to delineate clinical characteristics, surgical interventions, anatomic and visual outcomes of ruptured eye balls after trauma, and establish the prognostic indicators, which can assist clinicians in making correct surgical decisions during globe exploration for ruptured eyes. DESIGN: The study design used was a multicentre prospective cohort study, including six university-affiliated tertiary hospitals. PARTICIPANTS: We selected 242 cases of ruptured globe from the Eye Injury Vitrectomy Study database, until 31 December 2012. METHODS: All selected cases underwent vitreoretinal surgery, enucleation or evisceration, and were followed up for at least 6 months. Age, visual acuity (VA) after injury, ocular trauma zone, time to surgery, corneal laceration, scleral wound, extrusion of iris or lens, ciliary body damage, intraocular haemorrhage, retinal detachment or defect, proliferative vitreoretinopathy (PVR) and choroidal damage were the predisposing factors evaluated by logistic regression models. MAIN OUTCOME MEASURES: We compared the pre-surgical indicators between cases of anatomically restored eyes with VA of 4/200 or better, or eyes with initial no light perception restored light perception or better, and cases of VA worse than 4/200, silicone oil-sustained eyes, phthisis or enucleation. RESULTS: Nearly 40% of cases with ruptured globe were anatomically restored through vitreoretinal surgery. The closed-funnel retinal detachment or extensive retinal loss (odds ratio [OR] = 3.38, P = 0.026), PVR-C (OR = 3.45, P = 0.008), and choroidal damage (OR = 4.20, P = 0.004) were correlated with poor outcomes. CONCLUSION: The closed-funnel retinal detachment or extensive retinal loss, PVR-C, and choroidal damage are the risk factors for unfavourable outcomes in globe ruptures.

Six-month changes in cytokine levels after intravitreal bevacizumab injection for diabetic macular oedema and macular oedema due to central retinal vein occlusion.

BACKGROUND/AIMS: This study evaluated the impact of intravitreal injection of bevacizumab (IVB) on the microenvironment of the eyes of diabetic macular oedema (DMO) and macular oedema due to central retinal vein occlusion (CRVO-MO) patients. METHODS: This study comprised 136 patients, including 51 patients in the DMO group, 70 in the CRVO-MO group and 15 in the control group, who were followed for 6 months after IVB. Angiogenic cytokines, inflammatory cytokines and growth factors concentrations in the aqueous humour were measured before and after IVB using suspension array technology. We compared the levels of cytokines among DMO patients, CRVO-MO patients and control patients. We compared the levels of cytokines among groups according to the interval between the first and second injections of bevacizumab and according to the number of injections received during the 6-month follow-up period. RESULTS: Significantly higher concentrations of vascular endothelial growth factor (VEGF), transforming growth factor ß (TGF-ß), hepatocyte growth factor (HGF), interleukin 6 (IL-6), serum amyloid A (SAA) and monocyte chemoattractant protein-1 (MCP-1) were found in the aqueous humour of DMO and CRVO-MO patients compared with cataract patients. One month after IVB, the intraocular concentrations of VEGF were significantly decreased in the eyes of DMO (p=0.045) and CRVO-MO (p=0.002) patients compared with baseline. No other cytokine was significantly altered by bevacizumab therapy. CONCLUSIONS: Angiogenic, inflammatory and growth factors are involved in the development of DMO and CRVO-MO. In addition to VEGF, IVB did not cause significant differences in other inflammatory cytokines and growth factors in DMO and CRVO-MO patients.

An in situ-forming zwitterionic hydrogel as vitreous substitute.

Zwitterionic polymers have shown ultra-low biofouling properties at surfaces and excellent biocompatibility as implant. In this study, an in situ-forming zwitterionic hydrogel was designed and evaluated, both in vitro and in vivo, as a long-term vitreous substitute. The zwitterionic polymer poly(MPDSA-co-AC) was designed as a copolymer of the sulfobetaine methacrylamide and acryloyl cystamine monomers, providing the zwitterionic components and the thiol functional groups, respectively. The in situ gelation was via the thiol-ene Michael addition reaction with α-PEG-MA as the crosslinker. The gelation time, rheological properties, swelling profiles, and the transparency of zwitterionic hydrogels were studied in detail. Two systems with different crosslinker concentrations were tested in a rabbit model, and the one with the thiol-ene ratio of 2 : 1 showed excellent biocompatibility in vivo, formed space-filling hydrogels and remained transparent in the vitreous cavity for the 2 month implantation period. Therefore, in situ-forming zwitterionic hydrogels represent a promising material system as a vitreous substitute and possibly for other soft tissue replacements.