Anti-vascular endothelial growth factor (VEGF) drugs, including monoclonal antibodies (such as bevacizumab and ranibizumab) and fusion protein agents (such as aflibercept and conbercept) have been clinically proven to be effective to treat exudative age-related macular degeneration AMD). However, there are still some patients do not or poorly respond to the initial anti-VEGF agents, usually after several injections, ophthalmologists may switch to another anti-VEGF agent. In general, switching of anti-VEGF agent is considered for recurrent AMD, AMD resistance to anti-VEGF treatments. Current switching protocols include the replacement of monoclonal antibodies with fusion protein agents, the replacement of fusion protein agents with monoclonal antibodies, the substitution of one monoclonal antibody with another one, and the replacement of monoclonal antibodies with fusion protein agents and switching back with monoclonal antibodies. However, current researches on the switching of anti-VEGF drugs for exudative AMD are mostly retrospective and single-arm studies, and there are some differences in the results of different studies. Therefore, for patients with exudative AMD who do not respond to or respond poorly to anti-VEGF drugs, the efficacy of switching of anti-VEGF drugs is uncertain right now. Switching of anti-VEGF agents may improve the retinal anatomical outcome of the affected eye but may not necessarily improve visual acuity. Thus it is an option in the clinical practice to treat AMD. To determine the benefits of above mentioned switching regimens, randomized controlled clinical trials with large sample number and long study period will be needed.
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.
ObjectiveTo observe the clinical efficacy of intravitreal Conbercept on idiopathic choroidal neovascularization (ICNV). MethodsThis is an open and prospective study without control trial. Twelve eyes from 11 patients (7 females and 4 males) with ICNV diagnosed by best corrected visual acuity (BCVA), non-contact tonometer, ophthalmoscope, fundus photography, optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) were enrolled in this study. All affected eyes were treated with intravitreal Conbercept 0.05 ml (10 mg/ml) and received an average of (1.91±1.04) injections. The initial average letters of Early Treatment Diabetic Retinopathy Study (ETDRS) chart acuity were 61.73±14.58, range from 25 to 77. The patients were followed up for 6 to 9 months.The initial average central retinal thickness (CRT) was (330.73±47.79)μm, range from 290 to 467 μm. Best-corrected visual acuity (BCVA), OCT and ophthalmoscope examination were assessed monthly. ResultsDuring the 1, 3, 6 months after treatment, themean BCVA were all improved with statistically significant difference (t=2.68, 3.80, 3.65; P < 0.05). At 1 month later after treatment, the mean BCVA was obviously improved in 1 eye (9.09%), improved in 8 eyes (72.73%), stable in 1 eye (9.09%), decreased in 1 eye (9.09%). At 6 month later after treatment, the mean BCVA was obviously improved in 3 eyes (27.27%), improved in 6 eyes (54.55%), stable in 1 eye (9.09%), decreased in 1 eye (9.09%).During the 1, 3, 6 months after treatment, the mean CRT were all decreased with statistically significant difference(t=2.44, 3.78, 4.12; P < 0.05).At latest follow up, the leakage in macula lutea disappeared in 6 eyes(58.33%), decreased in 11 eyes (25%)and increased in 3 eyes (16.67%). There were no systemic or ocular serious side effects during the follow up. ConclusionIntravitreal Conbercept for ICNV showed CNV regression, retinal thickness reduction, visual acuity improvement and safety.
ObjectiveTo evaluate the efficacy and safety of intravitreal ranibizumab (IVR) for the treatment of retinopathy of prematurity(ROP). MethodsA total of 57 eyes of 29 premature infants with diagnosis of high-risk pre-threshold, threshold ROP, or aggressive posterior ROP were reviewed and analyzed in the study. The lesions of 18 eyes were located in zoneⅠ, 39 eyes were located in zoneⅡ. All infants in the study received IVR (10 mg/ml, 0.025 ml) as the initial treatment within 24 hours after diagnosis. Follow-up examinations were performed after treatment, every week at the first month, every 2 weeks at the second and third month, every month afterward, until vascularization of zoneⅢwas observed. Follow-up ranged from 16 weeks to 52 weeks, and the average follow-up time was (28.1±11.7) weeks. If the infants didn't respond positively to the treatment or the disease recurred, the additional treatments were applied. 36 eyes (63.2%) received a single injection, whereas 21 eyes (36.8%) received additional treatments. The follow-up examinations included the development of retinal vessels, the ocular or systemic adverse events. ResultsAmong the eyes, the development of peripheral retinal vessels could be observed in 36 eyes (63.2%) which received a single injection; clinical improvement in 11 eye (19.3%) which received repeat injection; stable disease in 10 eyes (17.5%) which received laser therapy. Among the eyes, 18 eyes (31.6%) recurred, including ggressive posterior ROP (14 eyes), threshold ROP (2 eyes) and high-risk pre-threshold ROP (2 eyes). The mean time of recurrence was (5.7±2.1) weeks (range 2.0-8.0 weeks). Three eyes (5.3%) of high-risk pre-threshold, threshold ROP lacked a positive response to the treatment. The lesions were controlled after additional laser given in these eyes. No serious ocular or systemic adverse events associated with the drug or the injection was observed during the follow-up period. ConclusionIVR is safe and effective for most ROP infants. In cases of recurrence or no response, conventional laser treatment or an additional IVR injection were needed.
Objective To evaluate the effectiveness of repeated intravitreal conbercept injection in patients with macular edema (ME) of retinal vein occlusion (RVO), guided by optic coherence tomography (OCT). Methods It is a retrospective case study. Forty patients (40 eyes) diagnosed as ME secondary to RVO were enrolled in this study. There were 19 males (19 eyes) and 21 females (21 eyes), with the mean age of (53.58±13.19) years and the mean course of 1.5 months. The best corrected visual acuity (BCVA), indirect ophthalmoscopy, fundus fluorescein angiography (FFA) and OCT were performed. The mean baseline of BCVA, central macular thickness (CMT) were 0.25±0.18 and (509.48±170.13) μm respectively. All the patients were treated with 10.00 mg/ml conbercept 0.05 ml (including conbercept 0.5 mg). Follow-up of these patients was 1 to 6 months after treatments, the BCVA, fundus manifestations, OCT were retrospectively observed by every month, the FFA was retrospectively observed by every 3 months. When there was retinal edema or CMT ≥50 μm by OCT during follow-up, those patients were retreated with intravitreal conbercept injection. The changes of the BCVA, CMT were evaluated before and after treatment. Meanwhile, complications in eyes related to medicine and treatment methods were evaluated too. Results At the 6 months, the BCVA was improved (increase≥2 lines) in 25 eyes (62.50%), stabilized (±1 line) in 13 eyes (32.50%) and decreased 2 lines in 2 eyes (5.00%). Retinal hemorrhage and exudates were absorbed in most patients. FFA showed no fluorescein leakage in 11 eyes (27.50%), minor fluorescein leakage in 26 eyes (65.00%), and retinal capillary non-perfusion in 3 eyes (7.50%). OCT showed absorption of the subretinal fluid. The mean CMT were (235.20±100.44) μm at 6 months. Intravitreal injection of conbercept was applied for 4 times in 8 eyes (20.00%), 3 times for 18 eyes (45.00%), and 2 times for 14 eyes (35.00%). The mean number of intravitreal injection was 2.85 times. There were no ocular or systemic adverse events observed in all patients. Conclusion Intravitreal conbercept injection is an efficacy and safe treatment for the patients with ME of RVO guided by OCT. It can stabilize and improve the visual acuity.
ObjectiveTo compare the efficacy of photodynamic therapy (PDT) alone or in combined with ranibizumab versus ranibizumab monotherapy (intravitreal injection, IVR) in patients with polypoidal choroidal vasculopathy (PCV). Methods80 eyes of 72 patients with PCV were enrolled into this retrospective and comparative study according to their therapeutic plan. 30 eyes of 28 patients, 28 eyes of 30 patients and 22 eyes of 21 patients were divided into PDT group, ranibizumab 0.5 mg group (IVR group) or the combination group, respectively. The patients with PCV were diagnosed according to clinical symptoms, optical coherence tomography (OCT) and fluorescent indocyanine green angiography (ICGA). The baseline best-corrected visual acuity (BCVA) before treatment was more than 0.05, and there was no retinal fibrosis and scar for all patients. There was no statistical difference of age (F=0.187), gender (χ2=0.423), average BCVA (F=1.120) and central retinal thickness (CRT) (F=0.431) among three groups (P > 0.05). They had not received any treatment before. Patients received verteporfin PDT in PDT group, 3 consecutive monthly IVRs starting day 1 in IVR group, and 3 IVRs after 3 days, 1 month, 2 months of PDT starting day 1 in combination group. Re-treatment was considered 3 months later if the follow up shown no changes in fundus photography, OCT and ICGA. The average follow-up time was 19 months. BCVA at baseline and follow-up visit at 1, 3, 6, 12 months was measured, and the proportion of patients with ICGA-assessed complete regression of polyps at month 6 was recorded as primary outcome. The CRT was measured at baseline and 6 months as secondary outcome. ResultsThere were significant difference of BCVA at 1, 3, 6 and 12 months among three groups(F=5.480, 5.249, 3.222, 4.711; P < 0.05). The average BCVA was significantly better at 1, 3, 6, 12 month than that at baseline(t=-6.632, -4.127, -3.904, -4.494; P < 0.05) in combination group, and was significantly better at 3, 6, 12 months than that at baseline (t=-5.636, -3.039, -3.833; P < 0.05) in IVR group. However there was no significant difference of the average BCVA in PDT group between follow-up at 1, 3, 6, l 2 months and baseline (t=1.973, 0.102, -0.100, -0.761; P > 0.05). The proportion of patients with complete regression of polyps at 6 months was higher in PDT (76.7%) or combination group (68.2%) than IVR group (35.7%) (χ2=0.003, 0.025; P < 0.05). There was no significant difference of CRT among 3 groups at baseline (P=0.651). The mean CRT decreased in all 3 treatment groups over 6 months (t=5.120, 3.635, 5.253; P < 0.05), but there was no significant difference of CRT among 3 groups (F=1.293, P > 0.05). ConclusionsThree therapies could effectively decrease CRT. IVR or IVR combined with PDT are both more effective than PDT therapy to improve vision of PCV patients. PDT or PDT combined with IVR was superior to IVR pnly in achieving complete regression of polyps in 6 months in PCV 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.
ObjectiveTo observe the concentration of the inflammatory cytokines in vitreous of severe proliferative diabetic retinopathy (PDR) after intravitreal ranibizumab injection (IVR). MethodsA total of 80 PDR patients (80 eyes) were enrolled in this study. The patients were randomly divided into vitrectomy group (group A) and IVR combined with vitrectomy group (group B), 40 eyes in each group. The differences of sex (χ2=0.05), age (t=0.59), duration of diabetes (t=0.36), HbA1c (t=0.13) and intraocular pressure (F=0.81) between two groups were not significant (P>0.05). The eyes in group B received 0.5 mg (0.05 ml) ranibizumab injection at 7 days before operation. The vitreous samples (0.4 ml) were obtained before operation. The concentration of vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-8, intercellular adhesion molecule-1 (ICAM-1) and connective tissue growth factor (CTGF) were measured by enzyme-linked immunosorbent assays. ResultsThe concentration of VEGF and ICAM-1 were (10.70±3.60), (224.64±90.32) pg/L in group B and (72.38±23.59), (665.61±203.34) pg/L in group A. The differences of VEGF and ICAM-1 concentration between two groups was significant (t=16.34, 12.53; P<0.001). The concentration of IL-6 and IL-8 were (210.64±80.27), (156.00±57.74) pg/L in group B and (45.78±33.82), (41.07±13.82) pg/L in group A. The differences of IL-6 and IL-8 concentration between two groups was significant (t=11.97, 12.24; P<0.001). There was no difference of CTGF concentration between two groups (t=1.39, P=0.17). The CTGF/VEGF in group B was higher than that in group A (t=14.75, P<0.001). ConclusionsOne week after IVR, the concentration of VEGF and ICAM-1 are decreased, while IL-6 and IL-8 increased. There is no obvious change in CTGF, but CTGF/VEGF is increased.
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 observe the inhibitory effects and characteristics of intravitreal injection with bevacizumab on laser induced choroidal neovascularization (CNV).Methods Twelve male brown norway（BN）rats were divided into the bevacizumab group and control group with six rats in each group. One eye of rats were received a series of 8 diode laser esions around optic disc to induce CNV,then the rats in bevacizumab group and control group underwent intravitreal injection with 2 mu;l bevacizumab and ringer's lactate.On days 7,14,and 21，the morphology and leakage of CNV were observed by fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA).On day 21 after photocoagulation,the photocoagulated eyes were enucleated and processed for histopathologic examination, including hematoxylin and eosin (Hamp;E) staining and immunohistochemistry staining for vascular endothelial growth factor（VEGF）.Results On day 7 after photocoagulation,ICGA showed that CNV developed in the bevacizumab group and the control group. FFA showed that leakage intensity in the bevacizumab group was significantly lower than that in the control group，but the bevacizumab group gradually increased over time. The mean thickness of CNV significantly decreased in the bevacizumab group.The CNV in the bevacizumab group were negative for VEGF according to the result of immmuohistochemistry staining.Conclusions Early intravitreal injection with 2 mu;l bevacizumab can reduce the thickness of CNV and inhibit the leakage of CNV. However, bevacizumab could neither block the formation of CNV, nor suppress the permeability permanently. Combined other therapies with bevacizumab may be more potential to treat CNV effectively.