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 evaluate the correlation between antiphospholipid (APLA) antibodies and retinal vein occlusion (RVO). Methods A computerized search was conducted in the Pubmed, Chinese Biological Medicine Database, China National Knowledge Infrastructure, VIP database, Wanfang Database combined with manually searching of literature reference proceedings. The search time was ranged from establishment of each database to August 1st, 2012. After the data extraction, quality of RCT was assessed. The meta analysis was performed by Stata 11.0. Results In total, 12 case-control studies (1324 subjects) that fulfilled the eligibility criteria were included in the meta-analysis involving 505 patients in RVO group and 819 subjects in control group. The odds ratio (OR) and 95% confidence interval (CI) of APLA, anticardiolipin antibodies (ACA), lupus coagulation inhibitor and RVO were 5.01 and 3.33 - 7.53,4.38 and 2.38 - 8.05, 1.72 and 0.73 - .88, 6.02 and 2.06 - 17.63, respectively. The OR and 95% CI of APLA, ACA, lupus coagulation inhibitor and branch RVO were 4.22 and 1.67 - 10.63, 3.69 and 1.32 - 10.32, 2.07 and 0.79 - 5.41, respectively. Conclusions APLA may increase the rick of RVO, especially ACA has a prediction function to RVO. It is necessary to screening for APLA in RVO patients.
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.
Objective To evaluate the clinical efficacy of intravitreal injections of antivascular endothelial growth factor monoclonal antibody ranibizumab in choroidal neovascularization (CNV) secondary to pathologic myopia (PM). Methods This is a prospective, uncontrolled, open-label study. 34 eyes of 34 patients with CNV secondary to PM were included in the study. All affected eye were treated with intravitreal ranibizumab 0.05 ml (10 mg/ml). Before the injection, bestcorrected visual acuity of early treatment of diabetic retinopathy study (ETDRS), noncontact tonometer, ophthalmoscope, fundus photography, fundus fluorescein angiograph (FFA) and optical coherence tomography (OCT) examination were necessary. The initial average letters of ETDRS acuity were 33.85plusmn;14.67, range from 0 to 69. The initial average central macular thickness (CMT) was（293.41plusmn;79.45） m, range from 210 m to 543 m. The patients were followed up for 3 to 12 months. Best-corrected visual acuity, OCT and ophthalmoscope examination were assessed monthly. If necessary, FFA was used. The letters of ETDRS acuity and CMT were compared before and after treatment. Results All eyes received an average of 1.68 injections, the final vision of follow-up increased （13.50plusmn;9.94） letters than before （t=7.92，P=0.00）, CMT decreased （71.14plusmn;72.26） m (t=4.62，P=0.00). There were no systemic or ocular serious side effects during the follow up. Conclusion Intravitreal ranibizumab for pathologic myopia choroidal neovascularization showed visual acuity improvement, retinal thickness reduction and safety.
Intravitreal injection of antiangiogenic agents is widely used to treat retinal vascular disease. This therapy can induce regression of neovascular vessels; reduce intraocular inflammation and retinal vascular permeability, and control macular edema. However the action period of these agents is short, and thus this therapy need repeated injections which cause higher operation risk and cost. Retinal laser photocoagulation therapy can close retinal capillary non-perfusion area and neovascular vessels, reduce macular edema caused by vascular leakage. However, as its therapeutic effect is based on the destruction of the retinal tissues in the lesion area, this therapy need longer time to show its effects. When the disease is controlled by this method, it may already induce some structural irreversible damages to the retina, especially the macular. This is why the visual acuity is not satisfactory in some patients, even though the disease get controlled, macular edema gets disappeared and anatomical structure of retina get improved. Properly evaluating all the pros and cons of retinal photocoagulation and intravitreal injection of antiangiogenic agents, will allow us to explore a better way to combine these two therapies to treat retinal vascular diseases.
The diagnosis and treatment of age-related macular degeneration (AMD) is an international hotspot of eye research. Successful clinical applications of antiVEGF drugs promoted both basic research and clinical practice of AMD. A number of countries and professional societies have established clinical guidelines for AMD management, including the epidemiology, risk factors, diagnosis, classification, and treatment process. These AMD guidelines are mostly based on recently published results of clinical trials, provided good model of evidence based medicine. It is urgent and necessary to have our own guideline which is suitable for Chinese patients. Reviewing and learning existed guidelines will help us to improve the clinical practice of AMD in China.
Objective To evaluate the efficacy and safety of intravitreal anti-vascular endothelial growth factor (VEGF) combined with photodynamic therapy (PDT) vs. photodynamic therapy for polypoidal choroidal vasculopathy (PCV).Methods A computerized search was conducted in Pubmed, OVID, Chinese Biological Medicine Database（CBM）,China National Knowledge Infrastructure （CNKI） by using key words ldquo;polypoidal choroidal vasculopathy, photodynamic therapy, intravitreal anti-VEGFrdquo; in Chinese and/or English combined with manually searching of bibliographies of pertinent articles, journals and literature reference proceedings. Randomized controlled trials (RCT) and non-RCT were collected. The search time was ranged from establishment of each database to September, 2011. The search was no 1imitation in language. The best corrected visual acuity (BCVA),resolution and recurring of lesions, decrease or complete resolution of pigment epithelial detachment （PED）,visual extinction or blindness rate,the rate of subretinal hemorrhage were analyzed by RevMan 5.0 software. Results In total, one RCT and four non-RCTs (273 patients) were included in the meta-analysis involving 148 patients in single treatment group and 125 patients in combined treatment group. The results of metaanalyses showed that there was no significant difference between two groups in the mean logarithm of minimal angle of resolution BCVA at six months ［standard mean difference=0.01, 95% confidence interval (CI): -0.12- 0.14,P=0.84］and 12 months ［standard mean difference = 0.04, 95%CI: -0.16-0.25,P=0.69 after treatment. There was no significant difference between two groups in the resolution of lesions ［odds ratio (OR)=1.38,95%CI:0.74-2.55,P=0.31］ at the months after treatment and decrease or complete resolution of PED (OR=0.67,95%CI:0.12-3.69,P=0.65) at 12 months after treatment. There was no significant difference between two groups in the recurring of lesions (OR=1.14, 95% CI:0.58-2.24,P=0.71) and lost of ge; three lines vision or blindness rate (OR=1.20, 95%CI:0.34-4.18,P=0.78) at 12 months after treatment. The rate of subretinal hemorrhage in combine treatment group was significant lower than single treatment group (OR=0.41, 95%CI:0.18 -0.94,P=0.04). Conclusions The incidence of subretinal hemorrhage occurred in patients with PCV after intravitreal anti-VEGF combined with PDT is much lower than that after single PDT.But the visual improvement, resolution of lesions and recurring of lesions of combined treatment need further studied to see if it is better than single PDT.
Objective To observe the effectiveness of combined therapy of intravitreal injections of ranibizumab and macular grid laser photocoagulation for branch retinal vein occlusion (BRVO) with macular edema (ME).Methods Forty-six patients of BRVO with ME were enrolled in this study. All the patients were examined for corrected visual acuity of Early Treatment Diabetic Retinopathy Study (ETDRS), slit lamp microscope, direct ophthalmoscope, intraocular pressure, fundus color photography, fundus fluorescein angiography and optical coherence tomography. The patients were divided into three groups by different treatments: injection group (18 eyes) received intravitreal injections of ranibizumab only, joint group (17 eyes) received intravitreal injections of ranibizumab combined with grid laser photocoagulation, and laser group (11 eyes) received laser photocoagulation only. The follow-up ranged from three to 15 months, with a mean of (8.0plusmn;3.2) months. The same equipment and methods were used to return visit in follow-up period. Repeated injections were adopted in injection group and joint group according to the results of subsequent visits. Then the repeated times of injection in two groups were compared. The visual acuity, macular retinal thickness (CRT) and ocular and systemic adverse reactions about drugs and treatments were followed up. The last follow-up time was considered as the judgment time for the therapeutic effects. Results The mean repeat times of injection in the injection group was 5.4plusmn;0.4, which more than that in the joint group 3.2plusmn;0.6 (t=12.17,P＜0.05). No ocular or systemic adverse events were observed in follow-up period. ETDRS visual acuity of injection group, joint group and laser group increased by 7.30plusmn;8.68,8.50plusmn;6.04,1.55plusmn;6.85 letters respectively after treatment. The differences were statistically significant before and after treatment in injection group and joint group (t=3.58, 5.78;P＜0.05), but there was no significant difference in laser group (t=0.75,P＞0.05). The difference was not statistically significant between injection group and joint group (t=0.45,P＞0.05). The difference was statistically significant between injection group and laser group, but also between joint group and laser group (t=2.13, 2.81;P＜0.05). CRT of injection group, joint group and laser group decreased by (110.56plusmn;43.08), (125.47plusmn;35.19), (50.73plusmn;19.68) mu;m respectively after treatment, with statistically significant differences (t=-10.89,-14.70, -8.55;P＜0.05). Conclusion In the treatment of BRVO with ME, intravitreal injection of ranibizumab combined with macular grid laser photocoagulation can reduce repeat times of injection, improve visual function and relieve ME.