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 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.
The introduction of anti-vascular endothelial growth factor (VEGF) therapy represents a landmark in the management of wet age-related macular degeneration (AMD). However, as a new therapy, several problems such as durability of the therapeutic effects, medication side effects, and medication selection have emerged. We should make appoint of improving the therapeutic effect and safety by realizing the limitation of the therapy, monitoring the clinical potential adverse reactions of anti-VEGF agents, and recommending individualized treatment.
Objective To observe the efficacy and safety of intravitreal injection of Ranibizumab(Lucentis) on exudative age－related macular degeneration (AMD). Methods To analyze retrospectively the clinical data of 56 patients with exudative AMD, which was diagnosed by examination of ETDRS charts, color fundus photograph, fluorescein angiography(FFA) or indocyanine green angiography(ICGA) and optical coherence tomography(OCT), were underwent intravitreal injection Lucentis 0.5 mg. Before the treatment, the ETDRS charts letter of 56 eyes was 25.1; choroidal neovascularization(CNA) was leaky which examined by FFA and ICGA; the average thickness of retina was 303.45 mu;m. Ranibizumab injection therapeutic times were 2.8, the average therapeutic times were 3.1. Follow－up time was 6－12 months (mean 8.7 months). Visual acuity (ETDRS charts letter), retinal thickness, leakage of CNV and operative complications before and after the treatment were analyzed. Results At the end of the follow－up period, the mean letter of ETDRS charts was 38.5, increased 13.4 letters (P＜0.01), the ETDRS charts improved 15 or more letters in 22 eyes (39.3%), decreased more than 15 letters in 2 eyes (3.6%); the foveal thickness on OCT images were 303.45 mu;m before treatment and 191.35 mu;m a fter treatment, decreased significantly (P＜0.00); FFA and/ or ICGA showed CNV complete closure in 12 eyes (21.4%), partial closure in 33 eyes (58.9%), no change in 9 eyes (16.1%) and new CNV in 1 eye (1.8%); Slight complications after operation disappeared during one week. Conclusion Intravitreal injection of Ranibizumab for exudative AMD was well tolerated, with an improvement in VA, FFA or ICGA , and OCT. (Chin J Ocul Fundus Dis,2008,24:160-163)
Objective To evaluate the efficacy and safety of photodynamic therapy (PDT) combined with intravitreal injection of bevacizumab for choroidal neovas cularization (CNV) caused by age-related macular degeneration (AMD). Methods A total of 21 eyes of 21 patients with AMD, which was diagnosed by examination of visual acuity, intraocular pressure, ocular fundus, fundus color photography, fundus fluorescein angiography(FFA), indocyanine green angiography(ICGA)and optic coherence tomography(OCT), were underwent PDT combined with intravitreal injection of Bevacizumab. The patients, 15 males (15 eyes) and 6 females (6 eyes), aged from 56 to 78 years, with the average of 68.6 years. The best corrected visual acuity：counting fingers/10cm0.9, logMAR was 1.04 plusmn; 0.41.CNV located in below or side central fovea of macula. There was obvious leakage of fluorescein which examined by FFA and ICGA. The average of retinal thickness of macular foveal was （258.91 plusmn; 78.66）mu;m. The treatment method of PDT has to according to the way of PDT for TAP and Verteporfin PDT for VIP. Intravitreal infection with 1.5mg bevacizumab was performed after three days under surface anesthesia. Follow-up time was 1, 3, 6, 12 months after the treatment. Results At last visit, the best-corrected visual acuity：counting fingers/10 cm 1.5, logMAR was 1.04plusmn;0.41, and the differences are statistically significant compared with before. The BCVA improved four or more lines in 6 eyes (28.57%), improved two to four lines in 9 eyes (42.86%), stabilized (plusmn;1 line or no change) in 6 eyes (28.57%) and decreased in none. The average intraocular pressure was （15.20plusmn;2.41）mmHg after surgery, and the differences was not statistically significant compared with before（P＞0.05）. FFA and ICGA showed CNV complete closure in 13 eyes (61.90 %), partial closure in 8 eyes (38.10%). The average of retinal thickness of mac ular foveal was（127.38plusmn;20.14） mu;m (P＜0.01). Conclusion Combining treatment with PDT and intravitreal injection of Bevacizumab is safe and effective for CNV which caused by AMD. It has significant improvement in BCVA, leakage of CNV and retinal edema. (Chin J Ocul Fundus Dis,2008,24:164-167)
Objective To observe the clinical effects and safety of Bevacizumab on recurrent idiopathic choroidal neoascularization(CNV). Methods To analyze retrospectively the clinical data of 21 eyes of 20 patients with recurrent idiopathic CNV who had intravitreal injection of Bevacizumab(0.05 ml 1.25 mg) after signing the letter of consent. In these patients, 12 cases (13 eyes) had been cured by photodynamic therapy (PDT), and 8 cases (8 eyes) had been cured by transpupillary thermotherapy (TTT). The follow-up periods were 2 weeks, 1 month, 3 months and 6 months after injection. The inspection findings of best-corrected visual acuity(BCVA), fundus fluorescein angiography (FFA) and optical coherence tomogr aphy (OCT) before and after the treatment were observed and analyzed. It could inject once more by the same way if there are recurrences in follow-up period. Results At the end of follow-up period, the BCVA improved obviously (gt;1 lines) in 14 eyes (66.7%)，kept stable (changed within 1 line)in 5 eyes (23.8%) and decreased (gt;1 lines) in 2 eyes(9.5%). The complete closure of CNV in 17 eyes (81.0%) and partial closure in 4 eyes (19.0%) were observed by FFA images. The thickness of retina in macular region decreased 115 micron. 3 eyes (14.3%) has inject again during follow-up period. The intraocular pressure increased in 4 eyes(19.0%) , the average intraocular pressure was 26.7 mm Hg（1 mm Hg=0.133 kPa). They have been returned to normal through the treatment. There was no serious adverse reaction in process of treatment. Conclusion Intravitreal infection of Bevacizumab can reduce the leakage of recurrent CNV and macular edema after PDT or TTT. About 2/ 3 patients can improve their visual acuity obviously. No severe complication or adverse reaction was observed in this study. (Chin J Ocul Fundus Dis,2008,24:168-171)
ObjectiveTo observe the clinical effect of microincision vitreoretinal surgery (VRS) assisted with intravitreal injection of ranibizumab (IVR) in severe proliferative diabetic retinopathy (PDR) treatment. MethodsThis is a prospective non-randomized controlled clinical study. A total of 60 patients (70 eyes) with severe PDR diagnosed were enrolled and divided into IVR group (31 patients, 35 eyes) and control group (29 patients, 35 eyes). IVR group patients received an intravitreal injection of 0.05 ml ranibizumab solution (10 mg/ml) first, and 3 or 4 days later they received 23G microincision VRS. Control group patients only received 23G microincision VRS. The follow-up time was 3 to 12 months with an average of (4.5±1.8) months. The logarithm of the minimal angle of resolution (logMAR) best corrected visual acuity (BCVA), intraocular pressure, the central retinal thickness (CRT) and retinal reattachment, and the incidence of postoperative complications were comparatively analyzed. ResultsThere was no topical and systemic adverse reactions associated with the drug after injection in IVR group. The incidence of post-operative vitreous hemorrhage (VH) in IVR group and control group was 8.6% and 28.6% at 1 week after surgery, 0.0% and 17.1% at 1 month after surgery, 0.0% and 8.6% at 3 month after surgery respectively. The differences were statistically significant for 1 week (χ2=4.63, P < 0.05) and 1 month (χ2=4.56, P < 0.05), but was not statistically significant for 3 months (χ2=0.24, P > 0.05). The mean post-operative logMAR BCVA of IVR group (0.81±0.40) and control group (1.05±0.42) have all improved than their pre-operative BCVA, the difference was statistically significant (t=12.78, 4.39; P < 0.05). The mean logMAR BCVA of IVR group is higher than BCVA of control group, the difference was statistically significant (t=-2.36, P < 0.05). The average post-operative CRT in IVR group was thinner than that of control group, the difference was statistically significant (t=-2.53, P < 0.05). The incidence of a transient high intraocular pressure in IVR group (14.3%) was lower than that in control group (34.3%), the difference was statistically significant (t=4.79, P < 0.05). The incidence of retinal reattachment (t=0.35), epiretinal membrane (χ2=0.97), neovascular glaucoma (χ2=0.51) was no difference between these two groups (P > 0.05). ConclusionThe minimally invasive VRS assisted by IVR treatment for severe PDR can effectively prevent postoperative VH, reduce CRT and improve visual acuity.