Outcomes of Eyes Lost to Follow-Up in Patients with Central Retinal Vein Occlusion Who are Receiving Anti-Vascular Endothelial Growth Factor Treatment.

BACKGROUND: To evaluate the anatomic and functional outcomes in eyes of patients with macular edema (ME) caused by central retinal vein occlusion (CRVO) who were lost to follow-up (LTFU) for more than 6 months following treatment with anti-vascular endothelial growth factor (VEGF) therapy and to determine the predictive factors of visual prognosis in these patients. METHODS: This study was conducted as a retrospective, case series investigation. Patients whose eyes were receiving intravitreal anti-VEGF treatment for CRVO-ME, with the next follow-up visit occurring more than 6 months following treatment were identified. Baseline disease characteristics (at the last visit before being LTFU), cause and duration of treatment interruption, and the resulting disease progression, complications, and outcomes were assessed. Baseline characteristics predictive of visual outcome were also analyzed. RESULTS: This study included a total of 17 eyes of 17 patients. The mean duration of being LTFU was 7.8 ± 2.1 months. On the return visit after being LTFU, 7 of 17 eyes (41.2%) developed neovascular complications. Despite treatment, 12 eyes (70.1%) lost ≥3 best-corrected visual acuity (BCVA) lines, with 2 eyes (11.8%) developing a final BCVA of hand motion or more severe. At the final visit, the mean logarithm of minimal angle of resolution (logMAR) BCVA deteriorated significantly compared to before being LTFU (P < 0.001). The increasing duration of being LTFU is associated with a deterioration of visual acuity prognosis. CONCLUSION: In CRVO-ME patients who are receiving anti-VEGF therapy, unintentional treatment interruptions can cause visually disastrous consequences, including irreversible blindness. Patients who were LTFU for a long period should be strongly warned about their poor visual prognosis.

AQUEOUS HUMOR CYTOKINE LEVELS AND REBOUND MACULAR EDEMA AFTER CONBERCEPT TREATMENT IN PATIENTS WITH CENTRAL RETINAL VEIN OCCLUSION.

PURPOSE: This study aimed to investigate the effect of intravitreal conbercept (IVC) injections on the aqueous humor concentrations of angiogenic and inflammatory cytokines in patients with macular edema (ME) due to central retinal vein occlusion and to determine whether changes in cytokine levels after IVC are associated with the development of rebound ME. METHODS: Forty-nine patients with ME caused by central retinal vein occlusion were included in this retrospective study. Monthly doses of IVC were administered for three months, followed by a Pro Re Nata dosing regimen. Rebound ME was defined as ≥110% increase in the foveal thickness compared with the baseline. Whenever injections were administered, aqueous humor samples were obtained. Multiplex bead assay was used to measure seven angiogenic and inflammatory cytokines in aqueous humor samples. RESULTS: At baseline, patients with central retinal vein occlusion showed significantly higher aqueous humor concentrations of vascular endothelial growth factor, placental growth factor, monocyte chemoattractant protein-1, platelet-derived growth factor-AA, IL-6, IL-8, and IL-12. At 1-month and 2-month follow-up after IVC, significantly decreased concentrations of all cytokines were observed. During the 12-month follow-up period, 6 of the 49 eyes (12.2%) showed rebound ME after IVC. Patients with rebound ME showed significantly elevated levels of inflammatory but not angiogenic cytokines. CONCLUSION: Angiogenic and inflammatory cytokines were overexpressed in patients with ME caused by central retinal vein occlusion. Conbercept treatment influenced the concentrations of various inflammatory cytokines and reduced aqueous vascular endothelial growth factor and placental growth factor concentrations. Rebound ME may occur due to disruption of the balance between angiogenic and inflammatory cytokines and an accompanying excess of inflammatory cytokines but not angiogenic cytokines, after antivascular endothelial growth factor therapy.

Comparison of the Effect of Intravitreal Conbercept and Ranibizumab on Aqueous Humor Cytokines in Central Retinal Vein Occlusion-Related Macular Edema.

Purpose: To analyze changes in the levels of angiogenic and inflammatory cytokines following the administration of intravitreal conbercept (IVC) or intravitreal ranibizumab (IVR) in patients with macular edema (ME) due to central retinal vein occlusion (CRVO). Methods: This retrospective study was conducted between June 2015 and January 2016 in The First Hospital of China Medical University. We administered 3 consecutive monthly doses of IVC (23 eyes) or IVR (19 eyes) in 42 eyes with CRVO-ME. At each injection, we collected aqueous humor samples and used multiplex bead assays to measure 7 angiogenic and inflammatory cytokines [vascular endothelial growth factor (VEGF), placental growth factor (PlGF), platelet-derived growth factor (PDGF)-AA, monocyte chemoattractant protein (MCP)-1, and interleukins (ILs)-6, 8, and 12]. Results: Visual acuity and ME improved significantly in both groups during the treatment period. Compared with the baseline, all the cytokine concentrations in the aqueous humor samples decreased significantly at 1 and 2 months after the initial dose of IVC or IVR. The improvement of visual acuity and ME and the changes of aqueous humor cytokine levels were similar in both groups. Concentrations of VEGF, PlGF, MCP-1, PDGF-AA, IL-6, IL-8, and IL-12 levels did not show significant intergroup differences after 1 month (P = 0.369, 0.312, 0.185, 0.353, 0.135, 0.487, and 0.337, respectively) and 2 months (P = 0.305, 0.376, 0.230, 0.519, 0.114, 0.960, and 0.830, respectively) of follow-up. Conclusion: IVC and IVR induced comparable improvements in clinical parameters, along with equivalent reductions in the concentrations of angiogenic and inflammatory cytokines in the aqueous humor.

Optical coherence tomography angiography characteristics in Waldenström macroglobulinemia retinopathy: A case report.

BACKGROUND: Waldenström macroglobulinemia (WM) is a distinct clinicopathologic entity characterized by the infiltration of the bone marrow by clonal lymphoplasmacytic cells that produce monoclonal immunoglobulin M (IgM) in the blood, and patients may present with symptoms related to the infiltration of the hematopoietic tissues or the effects of monoclonal IgM in the blood. Funduscopic abnormalities were noted in some of the patients due to hyperviscosity or other retinal lesions. Optical coherence tomography angiography (OCTA) as a non-invasive imaging tool can give qualitative and quantitative information about the status of retinal and choroidal vessels, which might be useful for diagnosing patients with WM-associated retinopathy. CASE SUMMARY: The patient was a 67-year-old man who presented with sudden visual disturbance in both eyes. Ophthalmic tests showed that best corrected visual acuity (BCVA) for this patient was 20/100 in the right eye and 20/1000 in the left eye. Fundus examination, optical coherence tomography (OCT), and OCTA revealed substantial bilateral optic disc edema, dilated and tortuous retinal veins, and diffuse intraretinal blot hemorrhages and edema which were consistent with bilateral central retinal vein occlusion (CRVO). Meanwhile, remarkable bilateral serous macular detachments (SMD) were noticed on OCT. Systemic examinations showed that the patient had anemia and extremely high level of monoclonal IgM and infiltration of clonal lymphoplasmacytic cells in bone marrow. The diagnosis of WM with hyperviscosity and retinopathy was made based on the clinical manifestation and laboratory findings. He was subsequently treated with intravitreal ranibizumab injection, plasmapheresis, and bortezomib plus rituximab with dexamethasone. Six months after treatments, the central macular volume decreased by 16.1% in the right eye and 28.6% in the left eye on OCT, and the patient's BCVA was improved to 20/60 in the right eye and 20/400 in the left eye. Very good partial response was obtained after systemic treatment. CONCLUSION: WM may affect visual function and present as bilateral CRVO. OCTA can show characteristic changes in both retina and choroid vasculatures, which might be of great value for diagnosing or following patients with WM retinopathy. Intravitreal anti-vascular endothelial growth factor treatment combined with systemic therapy might be beneficial for WM patients with retinopathy (SMD and CRVO).

Effect of Platelet-Activating Factor on Barrier Function of ARPE-19 Cells.

AIM: To examine the effects of platelet-activating factor (PAF) on the barrier functions of cultured retinal pigment epithelial (RPE) cells. METHODS: A human RPE cell line (ARPE-19) was cultured on microporous filter supports and treated with PAF and WEB 2086, a specific PAF-receptor (PAF-R) antagonist. The permeability of the RPE monolayer was measured using transepithelial electrical resistance (TER) and sodium fluorescein flux. The expression of the tight junction protein zonula occludens (ZO)-1 and the adherens junction protein N-cadherin was assessed using immunohistochemistry and Western blotting. We also measured the vascular endothelial growth factor (VEGF) concentrations in PAF-treated cultures and re-measured RPE monolayer permeability in the presence of VEGF-neutralizing antibodies. RESULTS: PAF significantly decreased the TER and enhanced the sodium fluorescein flux of the RPE monolayer and downregulated the expression of ZO-1 and N-cadherin. These effects were abolished by WEB 2086-mediated blockage of the PAF-R. PAF stimulation increased VEGF expression in RPE cells, and the antibody-mediated neutralization of VEGF caused a partial recovery of the barrier properties. CONCLUSION: The barrier functions of ARPE-19 cells were altered by PAF, and these effects were partly mediated by an upregulation of VEGF expression in these cells. Our results contribute to the growing body of evidence supporting the role of PAF in choroidal neovascularization. Our findings suggest that PAF is a novel target in the development of therapies for increased permeability of the RPE monolayer.

Assessment of conbercept therapy for high myopia macular neovascularization by optical coherence tomography angiography.

This study aimed to evaluate the efficacy and safety of the intravitreal injection of conbercept in the treatment of macular neovascularization (MNV) secondary to high myopia and to observe the application of optical coherence tomography angiography (OCTA) in the treatment follow-up. We reviewed the medical records of 20 patients (21 eyes) with MNV secondary to high myopia who were enrolled in the Department of Ophthalmology of the First Hospital of China Medical University between May 2018 and January 2020. Each patient received one or more intravitreal injections of conbercept (0.5 mg/0.05 mL). The treatment was conducted according to a 1 + PRN (pro re nata) regimen. The changes of best corrected visual acuity (BCVA), central macular thickness (CMT), and selected MNV and flow areas measured by OCTA were observed over a 6-month follow-up period. The mean logarithm of the minimum angle of resolution (logMAR) BCVA was 1.03 ± 0.61 before treatment and improved to 0.83 ± 0.59 (P = 0.007), 0.78 ± 0.62 (P = 0.001), 0.81 ± 0.73 (P = 0.027), and 0.79 ± 0.72 (P = 0.023) at 1 month, 2 months, 3 months, and 6 months after treatment, respectively. The mean CMT was 358.16 ± 206.11 µm before treatment and decreased to 295.38 ± 178.70 µm (P = 0.003), 288.34 ± 165.60 µm (P = 0.004), 284.36 ± 163.07 µm (P = 0.005), and 283.00 ± 160.32 µm (P = 0.004) at 1 month, 2 months, 3 months, and 6 months after treatment, respectively. Nineteen eyes (90.5%) had stable or improved vision at 6 months of follow-up. One month after conbercept injection, in OCTA images, the small-diameter blood vessels of the MNV decreased, the intertwined small blood vessels decreased or even disappeared, and the main or larger-diameter blood vessels were still present. The mean selected MNV and blood flow areas were 0.62 ± 0.81 and 0.22 ± 0.27 mm2, respectively, before treatment and decreased to 0.23 ± 0.33 and 0.07 ± 0.08 mm2 (P = 0.04 for both), respectively, 1 month after treatment. No drug-related systemic or ocular adverse effects were observed. Our results suggest that conbercept can effectively and safely improve BCVA and reduce CMT in patients with myopic MVN (mMNV). OCTA can be used to observe MNV area, blood flow area, and MNV morphological changes after treatment with conbercept, thus providing a reference for treatment follow-up.

Conbercept and Ranibizumab Pretreatments in Vitrectomy with Silicone Oil Infusion for Severe Diabetic Retinopathy.

PURPOSE: We compared the efficacies of intravitreal ranibizumab (IVR) and intravitreal conbercept (IVC) as the adjuvant pretreatments for vitrectomy with silicone oil infusion for tractional retinal detachment (TRD) secondary to proliferative diabetic retinopathy. METHODS: This retrospective study comprised 74 patients (79 eyes) who underwent vitrectomy with silicone oil tamponade for diabetic TRD. They received IVC (37 eyes) or IVR (42 eyes) at standard doses 3-5 days preoperatively and were followed up for ∼6 months. Anatomic success rate, intra- and postoperative complications, and visual outcomes were compared between both groups. RESULTS: Initial (IVC vs. IVR: 97% vs. 98%) and final anatomic success rates (100% in each group) and mean visual acuity changes were not significantly different (P = 0.46). Intraoperative complications [iatrogenic retinal breaks (P = 0.58) and intraoperative bleeding (P = 0.66)], postoperative complications [fibrin formation (P = 0.51), postoperative preretinal bleeding (P = 0.88), progressing or persistent neovascular glaucoma (P = 0.63), progressive fibrovascular proliferation (P = 0.93), and recurrent retinal detachment (P = 0.93)], and surgical variables [surgical time (P = 0.53)] were similar between both groups. CONCLUSIONS: Conbercept and ranibizumab are equally effective surgical adjuvants for vitrectomy with silicone oil infusion in patients with diabetic TRD.

Interleukin-13 and age-related macular degeneration.

AIM: o identify the effects of interleukin (IL)-13 on retinal pigment epithelial (RPE) cells and the IL-13 level in aqueous humor of age-related macular degeneration (AMD) patients. METHODS: IL-13 levels in aqueous humor specimens from AMD patients were detected with enzyme-linked immunosorbent assay (ELISA). ARPE-19 cells were treated with 10 ng/mL IL-13 for 12, 24, and 48h. The cell proliferaton was evaluated by the MTS method. The mRNA and protein levels of α-SMA and ZO-1 were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot respectively. The expression of tumor necrosis factor-α (TNF-α), transforming growth factor-ß (TGF-ß) and vascular endothelial growth factor (VEGF) were assessed by ELISA. RESULTS: IL-13 levels in the aqueous humor of patients with AMD were significantly higher than those in the control (167.33±17.64 vs 27.12±5.65 pg/mL; P<0.01). In vitro, IL-13 of high concentrations (10, 15, and 20 ng/mL) inhibited ARPE-19 cell proliferation. α-SMA mRNA in ARPE-19 cell were increased (1.017±0.112 vs 1.476±0.168; P<0.001) and ZO-1 decreased (1.051±0.136 vs 0.702±0.069; P<0.001) after treated with 10 ng/mL IL-13 for 48h. The protein expression of α-SMA and ZO-1 also showed the same tendency (α-SMA: P=0.038; ZO-1: P=0.008). IL-13 significantly reduced the level of TNF-α (44.70±1.67 vs 31.79±3.53 pg/mL; P=0.005) at 48h, but the level of TGF-ß2 was significantly increased from 34.44±2.92 to 57.61±6.31 pg/mL at 24h (P=0.004) and from 61.26±1.11 to 86.91±3.59 pg/mL at 48h (P<0.001). While expressions of VEGF didn't change after IL-13 treatment. CONCLUSION: IL-13 in vitro inhibit ARPE-19 cell proliferation and expression in the aqueous may be associated with AMD.

Interleukin-6 receptor blockade suppresses subretinal fibrosis in a mouse model.

AIM: To determine the involvement of the interleukin (IL)-6 with the development of experimental subretinal fibrosis in a mouse model. METHODS: Subretinal fibrosis was induced by subretinal injection of macrophage-rich peritoneal exudate cells and the local expression of IL-6 was assessed by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) at various time points. In addition, we investigated the effect of IL-6 receptor (IL-6R) monoclonal antibody (MR16-1) on subretinal fibrosis development. RESULTS: IL-6 mRNA level was significantly elevated at 1d after subretinal fibrosis induction and increased further to about 12-fold at 2d, reaching the peak. The result of ELISA showed that IL-6 protein was not detected in naive mice. At 2d after subretinal fibrosis induction, IL-6 protein level was upregulated to 67.33±14.96 pg/mg in subretinal fibrosis mice. MR16-1 treatment resulted in a reduced subretinal fibrosis area by 48% compared to animals from control group at 7d. CONCLUSION: Our results indicated that IL-6 signaling may contribute to the pathogenesis of subretinal fibrogenesis and IL-6R inhibition may provide an effective, novel treatment of advanced and late-stage neovascular age-related macular degeneration.

Bevacizumab vs ranibizumab for neovascular age-related macular degeneration in Chinese patients.

AIM: To compare the clinical efficacy of intravitreal injections of bevacizumab and ranibizumab for treating Chinese patients with neovascular age-related macular degeneration (AMD). METHODS: Among 60 Chinese patients with exudative AMD (60 eyes), 28 received intravitreal bevacizumab injections (1.25mg) and 32 received intravitreal ranibizumab injections (0.5mg), once a month for 3 months and were followed for a total of 6 months. Monthly optical coherence tomography (OCT) was used to determine whether the patients received additional treatments during the follow-up. We compared the baseline and 6-month follow-up values of mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) in both groups of patients. We also compared the occurrence of adverse events. RESULTS: At the 6-month follow-up, the mean BCVA (logMAR) of the bevacizumab and ranibizumab treatment groups improved from the baseline measurements of 0.72±0.23 and 0.73±0.22 to 0.47±0.14 and 0.45±0.20, respectively (P<0.05 for both groups). However, the change was not significantly different between the two groups. As evaluated by OCT, CRT decreased from 366.71±34.72µm and 352±36.9µm at baseline to 250.86±41.51µm and 243.22±41.38µm in the bevacizumab and ranibizumab groups, respectively (P<0.05 for both groups). However, the change was not significantly different between the two groups. There were no severe local adverse reactions or systemic adverse events. CONCLUSION: Intravitreal bevacizumab and ranibizumab have equivalent effects on BCVA and CRT and appeare safe over the short-term.

Transforming growth factor-ß neutralizing antibodies inhibit subretinal fibrosis in a mouse model.

AIM: To determine the involvement of the transforming growth factor (TGF)-ß with the development of experimental subretinal fibrosis in a mouse model. METHODS: Subretinal fibrosis was induced by subretinal injection of macrophage-rich peritoneal exudate cells (PECs) and the local expression of TGF-ß isoforms was assessed by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) at various time points. In addition, we investigated the effect of TFG-ß-neutralizing antibodies (TGF-ß NAb) on subretinal fibrosis development. RESULTS: TGF-ß1 and TGF-ß2 mRNA level was significantly elevated at day 2 after subretinal fibrosis induction and increased further to 5 and 6.5-fold respectively at day 5, reaching the peak. TGF-ß3 mRNA was not detected in the present study. The result of ELSIA showed that active TGF-ß1 and TGF-ß2 levels were upregulated to 10-fold approximately, while total TGF-ß1 and TGF-ß2 levels were even upregulated more than 10-fold and more than 20-fold respectively in subretinal fibrosis mice in comparison with naïve mice at day 5. TGF-ß NAb resulted in a reduced subretinal fibrosis areas by 65% compared to animals from control group at day 7. CONCLUSION: Our results indicate that TGF-ß signaling may contribute to the pathogenesis of subretinal fibrogenesis and TGF-ß inhibition may provide an effective, novel treatment of advanced and late-stage neovascular age-related macular degeneration.

Intravitreal bevacizumab as primary treatment of choroidal neovascularization secondary to punctate inner choroidopathy: results of a 1-year prospective trial.

PURPOSE: To evaluate the efficacy and safety of intravitreal bevacizumab as primary treatment of choroidal neovascularization secondary to punctate inner choroidopathy. METHODS: Twelve eyes of 12 patients with subfoveal or juxtafoveal choroidal neovascularization secondary to punctate inner choroidopathy received intravitreal bevacizumab injection (1.25 mg) in this prospective case series. Injection was repeated if persistent or recurrent activity of choroidal neovascularization was indicated by optical coherence tomography or fundus fluorescein angiography at 1-month intervals. Visual, clinical, angiographic, and anatomical changes were observed over a 12-month follow-up period. RESULTS: After 12 months of follow-up, mean logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.49 (20/62 in Snellen equivalent) at baseline to 0.23 (20/34 in Snellen equivalent; P < 0.001). Mean central retinal thickness determined by optical coherence tomography decreased from 333 µm to 241 µm (P < 0.001). All eyes (100%) had stable or improved vision, and 9 eyes (75%) showed an improvement of ≥ 2 lines. All lesions converted to the cicatricial phase after 12 months of follow-up. No drug-related systemic or ocular side effects were observed. CONCLUSION: Intravitreal bevacizumab is well tolerated and improves best-corrected visual acuity in choroidal neovascularization secondary to punctate inner choroidopathy over a 12-month period.

Increased nitric oxide and vascular endothelial growth factor levels in the aqueous humor of patients with coats' disease.

PURPOSE: To determine the aqueous humor levels of nitric oxide (NO) and vascular endothelial growth factor (VEGF) in the eyes of patients with Coats' disease and study the correlation between these levels. METHODS: Samples of aqueous humor were obtained from 7 patients with Coats' disease and 15 age-matched patients with congenital cataracts as controls. Nitrite and nitrate (NOx), the stable end products of NO, were detected by the Griess reaction, and VEGF levels were assessed by enzyme-linked immunosorbent assay. RESULTS: The aqueous humor NOx and VEGF levels were elevated in the eyes of patients with Coats' disease compared with those of controls (P=0.001 and P<0.001, respectively). The median NOx level was 55.2 µM (range, 23.0-75.3 µM) in the Coats' disease group and 18.8 µM (range, 8.7-36.2 µM) in the control group. The median VEGF level was 731.7 pg/mL (range, 288.3-1364.3 pg/mL) in the Coats' disease group and 33.3 pg/mL (range, 9.0-96.8 pg/mL) in the control group. No correlation was observed between the aqueous humor concentrations of NOx and VEGF. CONCLUSIONS: NOx and VEGF are increased but not related in the aqueous humor samples of patients with Coats' disease. NO and VEGF may play roles in the pathogenesis of Coats' disease. Further studies are needed to clearly elucidate the relationship among VEGF, NO, and other cytokines in Coats' disease.

Intravitreal bevacizumab for treatment of subfoveal idiopathic choroidal neovascularization: results of a 1-year prospective trial.

PURPOSE: To evaluate the visual and anatomic outcomes of intravitreal bevacizumab in patients with subfoveal idiopathic choroidal neovascularization (CNV). DESIGN: Prospective, nonrandomized, interventional case series. METHODS: Forty patients with subfoveal idiopathic CNV were included in this clinical trial. Their eyes were treated with a single intravitreal injection of 1.25 mg bevacizumab followed by as-needed dosing indicated by the presence and recurrence of intraretinal edema, subretinal fluid (SRF), or pigment epithelial detachment (PED), based on optical coherence tomography (OCT) performed monthly. Visual, clinical, angiographic, and anatomic changes were observed over a 12-month follow-up period. RESULTS: After 12 months of follow-up, the mean logarithm of minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA) improved from 0.53 (20/68 in Snellen equivalent) at baseline to 0.29 (20/39 in Snellen equivalent; P < .001). Mean central retinal thickness determined by OCT decreased from 321 µm to 237 µm (P < .001). All eyes (100%) had stable or improved vision, and 28 eyes (70%) showed an improvement of 2 lines or more. All lesions were in the cicatricial stage of CNV at 12 months of follow-up, with no leakage of fluorescein in the late phase of fluorescein angiography and no intraretinal edema, SRF, and/or PED detected by OCT. No drug-related systemic or ocular side effects were observed. CONCLUSIONS: Intravitreal bevacizumab is generally well tolerated and improves BCVA in eyes with subfoveal idiopathic CNV over a period of 12 months. Large, randomized, controlled, long-term clinical trials are required to further evaluate the efficacy and optimal strategy of this treatment modality.

Intravitreal bevacizumab for treatment of macular edema secondary to central retinal vein occlusion: eighteen-month results of a prospective trial.

PURPOSE: The purpose of this article was to evaluate the efficacy and safety of intravitreal bevacizumab (Avastin) in eyes with macular edema secondary to central retinal vein occlusion (CRVO). METHODS: Forty-five consecutive eyes with macular edema secondary to CRVO were included in a prospective clinical trial. Eyes were treated with 3 initial intravitreal bevacizumab injections of 1.25 mg at monthly intervals. Retreatment was based on central retinal thickness (CRT) measured by optical coherence tomography (OCT). OCT was performed monthly; fluorescein angiography was performed every 3 months. Main outcome parameters were visual acuity (VA, using the Early Treatment of Diabetic Retinopathy Study protocol) and CRT in an 18-month follow-up period. RESULTS: After 18 months of follow-up, mean VA increased from 40.9 letters at baseline to 61.9 letters (+21 letters; P<0.001) at month 18; CRT decreased from 572.3 µm at baseline to 273.2 µm at month 18 (-299.1 µm; P<0.001). Neither age, duration of CRVO, baseline VA, nor baseline CRT was correlated with the change in VA. No drug-related systemic or ocular side effects were observed following intravitreal bevacizumab treatment. CONCLUSIONS: Intravitreal bevacizumab is generally well tolerated and may improve VA and decrease CRT in patients with macular edema secondary to CRVO over a period of 18 months.

CTGFsiRNA ameliorates retinal cells apoptosis in streptozotocin-induced diabetic rats.

AIM: To detect the effect of connective tissue growth factor (CTGF) on the apoptosis in the diabetic retina with small interfering RNAs (siRNA) targeting CTGF. METHODS: A total of 60 rats were divided into 6 groups including control group, diabetic 4, 8, 12, 16 weeks groups, and interference group. Diabetic rats were induced by intraperitoneal streptozotocin (STZ). Retinas were obtained from control, diabetic rats and diabetic rats of interference group treated by intravitreal injection of CTGFsiRNA to suppress the expression of CTGF mRNA. Retinal cells apoptosis was detected by Tunnel staining and mRNA expression of CTGF was analyzed by RT-PCR. RESULTS: The levels of CTGF and the apoptosis in the retinas of diabetic rats were significantly higher than those in the controls. Apoptosis occurred at 4 weeks after a diabetic model being set up, became serious with the diabetes developing, while CTGF elevated at 8 weeks. The apoptosis cell counts increased to 25.8cells/mm(2) at 24weeks of diabetes. SiRNA-mediated inhibition of CTGF mRNA resulted in a significant decrease in apoptosis. Significant correlations were found between CTGF and apoptosis in the retina. CONCLUSION: It was suggested that CTGF might be involved in retinal cells apoptosis which is a characteristic of early diabetic retina. SiRNA targeting CTGF seems to have the advantage of ameliorating retinal cells apoptosis.

Neuroprotective effect of recombinant human erythropoietin on optic nerve injury in rats.

BACKGROUND: Optic nerve injury, caused by retinal and optic nerve diseases, can eventually result in vision loss. To date, few effective treatments have been discovered to restore visual function. Previous studies showed that recombinant human erythropoietin (rhEPO) has a neuroprotective effect on the central nervous system, particularly in nerve injury. In this study, we investigated the effects of rhEPO on axonal regeneration and functional restoration following optic nerve injury. This was done by measuring the expression of growth associated protein 43 (GAP-43), a marker for neuronal regeneration, on the retina and flash-visual evoked potential (F-VEP). METHODS: Adult Wistar rats were randomly assigned to rhEPO and control (saline) groups. Optic nerve crush injury models were established and rhEPO or saline were immediately injected into the vitreous cavity. The expression of GAP-43 was detected by immunohistochemistry and the F-VEP was measured pre-injury, immediately after injury, 1 week and 2 weeks post-injury. RESULTS: No detectable staining for GAP-43 was observed in normal retina. In the control group, the level of GAP-43 expression was higher at 1 week post-injury, but decreased at 2 weeks. In the rhEPO group, the level of GAP-43 expression was notably higher at both 1 week and 2 weeks. At each time point post-injury, the expression of GAP-43 in rhEPO group was significantly higher than the control group (P < 0.05). Obvious changes in F-VEP examination were detected immediately after optic nerve injury, including significantly prolonged latency and decreased amplitude of the P1 wave. In the control group, the changes were still obvious at 1 week. The latency was decreased and the amplitude had slightly recovered to 28.23% of the normal value at 2 weeks. In rhEPO group, there was significantly more recovery than the control group at 1 week and 2 weeks post-injury (P < 0.05). The latency most close to the normal level and the amplitude had recovered to 65.51% of the normal value at 2 weeks. CONCLUSIONS: rhEPO can prolong the expression of GAP-43 and increase its intensity after optic nerve injury, thereby promoting neural repair and axonal regeneration. Under the protection of rhEPO, the conduction velocity of the optic nerve recovered significantly. Therefore, rhEPO has neuroprotective effects on the optic nerve and promotes functional restoration of the optic nerve.

Studies on the protective immunity of Schistosoma japonicum bivalent DNA vaccine encoding Sj23 and Sj14.

In order to explore the high performance bivalent DNA vaccine of Schistosoma japonicum, the fatty-acid-binding protein (Sj14) and the 23 kDa transmembrane protein (Sj23) two proteins were selected to construct the DNA-based vaccine. It was successful to construct a bivalent DNA vaccine using three strategies: the co-expression of two genes, a fusion gene expression and two kinds of plasmids in combination (cocktail vaccine). The bivalent DNA was proven to express well in vitro and in vivo by indirect immunofluorescence test (IIF) and reverse transcriptase-polymerase chain reaction (RT-PCR). The protective immunity of bivalent DNA vaccine was higher than that of univalent DNA vaccine (p<0.05). There were four groups of bivalent vaccine whose protective immunity was higher than 50%. Granuloma diameter reduction rates were in the range of 18-39%. There was no significant impact on immunity protection exerted by the four factors including dosage, inoculated times, inoculated routes and challenge time after the last immunization in three levels (p>0.05).

[A comparison of the mRNA expression of VEGF and its receptor FLK-1 in rabbit iris pigment epithelium cells and retinal pigment epithelial cells].

OBJECTIVE: To investigate mRNA expression of vascular endothelial growth factor (VEGF) and its receptor FLK-l in iris pigment epithelium (IPE) cells and retinal pigment epithelium (RPE) cells, and the feasibility of transplantation of autologous IPE cells to substitute RPE in the treatment of age-related macular degeneration (AKMD) and diseases of RPE dysfunction. METHODS: IPE and RPE cells were isolated from pigmented rabbits. The expression of mRNA for VEGF and FLK-l were detected by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Rabbit IPE and RPE cells express VEGF mRNA and FLK-l; the express of VEGF and FLK-1 mRNA in IPE cells was relatively low compared with the expression in RPE cells. The amount of VEGF mRNA in IPE cells was 44.62% of RPE cells, and amount of FLK-l mRNA was 52.36% of RPE cells- The results of the differences of expression of VEGF and FLK-l mRNA between IPE and RPE cells was statistically significant (t-test, P < 0.001). CONCLUSIONS: VEGF and FLK-l mRNA in IPE cells express is relatively low compared with the expression in RPE cells, and the results suggest that IPE cells could be more beneficial than RPE cells in the transplantation into the subretinal space.