Diabetic macular edema (DME) is a common ocular complication of diabetes patients. It mainly involve macular which is closely related with visual function, thus DME is one of the major reasons causing visual impairment or blindness for diabetes patients. How to reduce the visual damage of DME is always a big challenge in the ophthalmic practice. In the past three decades, there are tremendous developments in DME treatments, from laser photocoagulation, antiinflammation drugs to antivascular endothelial growth factor therapy. However, the mechanism of DME development is not yet completely clear; every existing treatment has its own advantages and weaknesses. Therefore DME treatment still challenges us to explore further to reduce the DME damages.
Objective To observe the effects of dual targets intervention on the expression of vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) in diabetic rat retina. Methods Forty-eight Sprague -Dawley rats were randomly divided into control group (CON1 group) and diabetes mellitus group (DM group). The rats of DM group were induced with streptozotocin injection creating a diabetic model. Retinas were obtained at eight, 10, 12 weeks after DM induction from both groups. CTGF and VEGF mRNA levels were examined by realtime reverse transcriptionpolymerase chain reaction (RT-PCR). Based on the results of above experiments, 60 rats with same conditions were selected. Fifty rats were induced with streptozotocin injection creating a diabetic model, and 10 rats comprised the control group (CON2 group). Then the 50 diabetic rats were randomly divided into ranibizumab and CTGF shRNA dual targets intervention group, ranibizumab singletarget intervention group, CTGF shRNA singletarget intervention group and nonintervention group. Retinas were obtained at one week after intervention from all the groups. CTGF and VEGF mRNA levels were examined by RT-PCR. Results The levels of CTGF mRNA were significantly higher in DM group than that in CON1 group at the 8th weeks after DM induction, and this upregulation was maintained through the 12th week (t=-2.49, -2.67, -2.42;P＜0.05). There was no difference on VEGF mRNA levels between DM group and CON1 group at the 8th weeks after DM induction(t=-0.443,P=0.669). VEGF mRNA levels of DM group started to be significantly elevated over those in the CON1 group at the 10th week, and remained to be higher at the 12th week (t=-2.35, -2.57;P＜0.05). The VEGF mRNA of ranibizumab single-target intervention group was significantly lower than that in non-intervention group (t=-3.44,P=0.014), which was similar to CON2 group (t=-1.37,P＞0.05); however, the CTGF mRNA level was significantly increased as compared to the nonintervention group (t=2.48,P＜0.05). In the CTGF shRNA single-target intervention group, the levels of CTGF and VEGF mRNA were decreased as compared to the non-intervention group (t=0.23, -2.92;P＜0.05). In the ranibizumab and CTGF shRNA dual targets intervention group, the levels of CTGF and VEGF mRNA were decreased as compared to the non-intervention group (t=-6.09, -5.11;P＜0.001), which was similar to CON2 group (t=-1.16, 1.139; P＞0.05). Conclusions Both CTGF and VEGF gene expression are up-regulated in early diabetic rat retina, and the level of CTGF increased earlier than VEGF. Ranibizumab combined with CTGF shRNA could simultaneously reduce the level of CTGF and VEGF mRNA in diabetic rat retina.
Objective To observe the effect of pars plana vitrectomy (PPV) with epiretinal membrane peeling (ERMP) and (or) internal limiting membrane peeling (ILMP) and silicone oil tamponade for highly myopic macular hole retinal detachment (MHRD) with posterior staphyloma. Methods Eighty-five highly myopic MHRD patients (85 eyes) were enrolled in this study. All the patients were examined for corrected visual acuity (CVA), slit lamp microscope and preset lens, indirect ophthalmoscope, A/B ultrasound, optical coherence tomography (OCT) and intraocular pressure examination. The average axial length was (29.1plusmn;1.8) mm. There were 24 eyes with diffuse choroid atrophy and 61 eyes with partial choroid atrophy. The CVA was converted into a logarithm of the minimal angle of resolution (logMAR) for statistical analysis. The average logMAR CVA was 1.93plusmn;0.37. All the patients were treated with PPV and triamcinolone acetonide or indocyanine green (ICG) assisted ILMP and (or) ERMP and silicone oil tamponade. TA assisted ERMP was performed in 21 eyes; with ICG assisted ILMP in 56 eyes and TA assisted ILMP in eight eyes. The duration of silicone oil tamponade was (6.2plusmn;1.6) months. CVA, retina and macular hole status and complications were observed postoperatively. Differences between preoperative and postoperative CVA were evaluated by the t test and correlation analysis. Multiple logistic regression analysis was performed to assess the influence of individual preoperative factors on the initial anatomical success. Differences in the macular hole closure rate between eyes with or without macular schisis were evaluated for statistical significance using corrected chi-square. Results The mean logMAR CVA was 1.34plusmn;0.48 after surgery, which significantly improved compared to that before surgery (t=39.38, P＜0.01). The CVA after surgery was independent of axial length (r=0.142, P＞0.05), choroid atrophy (t=0.23, -0.165,P＞0.05) and macular hole closure (t=0.12, -0.005, P＞0.05). The retina reattached in 79 eyes (92.9%) and recurrence of retinal detachment occurred in six eyes (7.1%). Multiple logistic regression analysis indicated that recurrence of retinal detachment was independent of choroid detachment, proliferative vitroretinopathy, axial length, choroid atrophy and ILMP (OR=1.428, 5.039, 0.815, 2.578, 0.432; P＞0.05). Of these 85 eyes, macular hole closed in ten eyes (11.8%), macular hole did not close in 75 eyes (88.2%). There were 24 eyes (28.2%) experienced high intraocular pressure during the first 2 weeks after surgery, all of them were under control with drugs. There were 12 eyes (14.1%) presented with high intraocular pressure before the silicone oil removal, all of them were under control only by silicone oil removal. Conclusion For the treatment of MHRD with posterior staphyloma, PPV combined with ERMP and (or) ILMP and silicone oil tamponade show a high retinal reattachment rate.
Objective To compare the outcome of C3F8 versus silicone oil intraocular tamponade after pars plana vitrectomy (PPV) for the treatment of severe highly myopic macular hole retinal detachment (MHRD). Methods Thirty-two highly myopic MHRD patients (32 eyes) with extreme long axial lengths (ge;29.0 mm), quot;severequot; retina pigment epithelium (RPE) and chorioretinal atrophy, and posterior staphyloma who underwent PPV, were enrolled in this study. The patients were divided into two groups according to different intraocular tamponade agents: C3F8 (group A, 15 eyes) and silicone oil (group B, 17 eyes). The patients with retinal re-detachment after surgery received PPV again. The differences of sex (P=1.000), age (t=0.444, P=0.660), best-corrected visual acuity (t=0.084, P=0.934), diopter (t=0.449, P=0.978), lens state (P=1.000), time of the symptoms (t=0.375, P=0.710) and degree of retinal detachment (chi;2=0.014, P=0.907) between group A and B were not statistically significant. The anatomic reattachment of the retina, macular hole closure, and vision acuity were observed at one week, one, three, six and 12 months after surgery. Results The rates of retinal reattachment and macular hole closure were 60.00% and 13.33 % in group A, 82.35% and 29.41% in group B in the first time of surgery. There was no difference in rates of retinal reattachment and macular hole closure between two groups (P=0.243, 0.402). The rates of retinal reattachment and macular hole closure were 86.67% and 20.00% in group A, 94.12% and 29.41% in group B in the second time of surgery. There was no difference in rates of retinal reattachment and macular hole closure between two groups (P=0.589, 0.691). Twelve months after surgery, the vision acuity improved in five eyes, unchanged in seven eyes , and decreased in three eyes in group A; the vision acuity improved in seven eyes , unchanged in eight eyes , and decreased in two eyes in group B. The differences of vision result was not statistically significant between two groups (chi;2=0.209, P=0.647). Conclusion The rates of retinal reattachment and macular hole closure with silicone oil tamponade was higher than that with C3F8 tamponade in eyes with severe highly myopic MHRD, but the differences are not statistically significant.
Objective To observe the effect of tetramethypyrazine (TMP) on the expression of hypoxia-related factors in human umbilical vein endothelial cells (HUVECs). Methods The second to fifth passage cultured HUVECs were divided into five groups: control group, CoCl2induced hypoxic group and 50, 100, 200 mu;mol/L TMP treatment groups. HUVECs in control group were not treated. HUVECs inCoCl2induced hypoxic group were treated with 150 mu;mol/LCoCl2for four hours. HUVECs in 50, 100, 200 mu;mol/L TMP treated groups were pretreated with 150 mu;mol/LCoCl2 for four hours, followed by treatment with 50, 100, 200 mu;mol/L TMP for eight hours. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA levels of prolyl hydroxylase 2 (PHD2), hypoxia-induced factor-1alpha;(HIF-1alpha;) and vascular endothelial growth factor (VEGF). Protein levels of PHD2, HIF-1alpha;, and VEGF were detected using Western blot. Results Compared with the control group, theCoCl2 induced hypoxic group showed decreased mRNA and protein levels of PHD2 (t=3.734, 3.122;P＜0.05), while those of HIF-1alpha; and VEGF increased (HIF-1alpha; mRNA:t=4.589,P＜0.05; HIF-1alpha; protein:t=3.778,P＜0.05. VEGF mRNA:t=3.926,P＜0.05; VEGF protein:t=3.257,P＜0.05). Compared with theCoCl2 induced hypoxic group, 50, 100, 200 mu;mol/L TMP treated groups showed increased mRNA and protein levels of PHD2 (PHD2 mRNA: t=3.286, 3.617, 3.886;P＜0.05. PHD2 protein: t=2.813, 3.026, 3.078; P＜0.05); while those of VEGF decreased (VEGF mRNA: 50 mu;mol/L TMP: t=1.696,P＞0.05; 100 mu;mol/L TMP:t=2.974,P＜0.05; 200 mu;mol/L TMP: t=3.492,P＜0.05; VEGF protein: 50 mu;mol/L TMP: t=1.986,P＞0.05; 100 mu;mol/L TMP: t=2.976,P＜0.05; 200 mu;mol/L TMP:t=3.136,P＜0.05); although changes in HIF-1alpha;mRNA levels were not statistically significant (t=1.025, 0.726, -1.386;P＞0.05), showed a decrease in HIF-1alpha;protein levels (50 mu;mol/L TMP: t=2.056,P＞0.05; 100 mu;mol/L TMP:t=3.058,P＜0.05; 200 mu;mol/L TMP:t=3.828,P＜0.05). ConclusionIn HUVECs, TMP can upregulate the mRNA and protein expression of PHD2, while down regulating HIF-1alpha; protein expression and VEGF mRNA and protein expression under acute hypoxic conditions.
Objective To investigate the effect of photodynamic therapy (PDT) combined with intravitreal bevacizumab on wet age-related macular degeneration (AMD). Methods In this retrospective study, 34 eyes (28 cases) diagnosed with wet AMD received PDT combined intravitreal injection of bevacizumab, including 25 eyes with classic CNV and 9 eyes with minimally classic CNV by fluorescein angiography; On optical coherence tomography (OCT), 23 eyes showed intraretinal fluid (IRF) and 11 eyes presented subretinal fluid (SRF). After signing informed consent, all patients underwent initial standard PDT followed by intravitreal bevacizumab (1.25 mg) within succeeding 3 to 7 days. Best corrected visual acuity (BCVA) and OCT with routine eye examinations were evaluated monthly. Additional bevacizumab (1.25 mg) was injected intravitreally if new or increasing fluid appreciated on OCT, or BCVA lowered more than 5 letters even with stabilized fluid. Injection was discontinued if no fluid was showed on OCT (quot;dry macularquot;), or BCVA was stabilized even with fluid after two consecutive injections. BCVA and central retinal thickness (CRT) were analyzed and compared between baseline and 6 month follow-up. The correlation between parameters such as baseline BCVA, greatest linear dimension (GLD), type of CNV, SRF or IRF and posttreatment BCVA will be analyzed. The injection number of bevacizumab and complications were recorded. Results Compared to baseline, BCVA improved (9.4plusmn;10.2) letters and reach 44.9plusmn;21.3 letters (t=5.438，P＜0.01) and CRT decreased (184.6plusmn;214.6) mu;m (t=4.810，P＜0.01) at 6 month visit. The average of injection number was 1.9plusmn;0.9 (including initial injection of combination therapy). With multiple lineal regression analysis, only baseline BCVA correlated to posttreatment BCVA at 6 month visit (r=0.802.P＜0.01). The type of CNV, GLD, SRF or IRF on OCT and CRT at baseline were not associated to post-treatment BCVA (r=0.053, -0.183, 0.139 and 0.053, respectively.P＞0.05). BCVA of eyes with SRF (14.7 letters) increased more than eyes with IRF (6.9 letters) on OCT (t=-2.207，P=0.035). The change of BCVA after treatment (t=-0.076), change of CRT (t=-1.028) and number of injections (Z=-1.505) were not different between classic CNV and minimally classic CNV (P＞0.05). The change of CRT (t=-0.020) and number of injections (Z=-0.237) did not present difference between SRF and IRF (P＞0.05). The change of BCVA (t=1.159) and number of injections (Z=-1.194) were not correlated to whether residual fluid or not at 6 month visit (P＞0.05). No severe complications were noticed during follow-up.Conclusion For wet AMD patients, PDT combined intravitreal bevacizumab could improve visual acuity, reduce retinal thickness and control CNV progress in a short-term.
Objective To compare the clinic therapeutic effect of intravitreal ranibizumab injection versus photodynamic therapy (PDT) combined with intravitreal ranibizumab injection for idiopathic choroidal neovascularizatio (ICNV), and to investigate the clinical effect and safety of treatment. Methods A randomized controlled clinical prospective study was performed for 27 patients (27 eyes) diagnosed as ICNV. Fourteen patients were assigned to receive PDT and intravitreal ranibizumab injection (combination roup.n=14); the control group was treated with only intravitreal ranibizumab injection (single group, n=13).The combination group was treated with an intravitreal injection of ranibizumab (0.5 mg/0.05 ml) 1 week after PDT. The bestcorrected visual acuity (BCVA) (logMAR), examination of the ocular fundus, fluorescence fundus angiography (FFA), indocyanine green angiography (ICGA) and optical coherence tomography (OCT) were performed respectively at 1, 2, 3, 6 and 12 months after treatment. If choroidal neovascularization (CNV) was only partially regressed or the leakage went on during follow-up, those patients were re-injected with ranibizumab. Results After 12 months, the average vision is 0.22plusmn;0.11 in single group, and 0.21plusmn;0.12 in combination group, and the differences were not significant (t=0.187, P=0.853). In single group FFA and ICGA showed completely closed CNV in 10 eyes (77.92%), and almost closed CNV in 3 eyes (23.08%) with obvious reduction of fluorescence leakage. In combination group FFA and ICGA showed completely closed CNV in 12 eyes (85.71%), and almost closed CNV in 2 eyes (14.29%) with obvious reduction of fluorescence leakage; OCT showed the subretinal fluid absorption and reduction of CNV. The average macular retinal thickness (MRT) in single groups is （167.96plusmn;10.69） m, and in combination groups is （171.64plusmn;11.30）m. In single and combination groups MRT decreased significantly at the final follow-up, but no significant differences in both groups (t=-0.887.P=0.389). The average number of intravitreal injection was （1.5plusmn;0.7） in combination group and （2.4plusmn;1.0） in single group (t=2.821，P=0.009). There were no ocular or systemic adverse events observed except for one patient with subconjunctival hemorrhage in the single group.Conclusions Intravitreal ranibizumab injection and PDT combined with intravitreal bevacizumab injection are both effective and safe for the patients with ICNV. The combined therapy can induce CNV regression, fundus hemorrhage and exudation absorption more effectively, and have less recurred CNV and side effects.