Objective To observe the retinal toxicity of intravitreal injection of Bevacizumab (Avastin) in albino rabbit eyes at different doses. Methods Sixteen New Zealand albino rabbits，thirty-two eyes were divided into four groups at random. Three groups were prepared for Avastin experiment, named A, B, C. Each group received intravitreal injection of Avastin at dose 1.25 mg/0.05ml，2.5 mg/0.1ml and 6.25 mg/0.25 ml respectively. The other group named D served as a control, and accepted intravitreal injection of 0.9% normal saline 0.1 ml. Then test it by electroretinagram (ERG) after 1, 2 and 4 weeks. In addition, each group was removing two rabbitprime;s eyes to observe the retinal morphology and ultra structure by light microscope and transmission electron microscopy after intravitreal injection avastin 1, 2 and 4 weeks. Results The ERG pattern and amplitude of each group were normal after intravitreal injection Avastin 1, 2 and 4 weeks. （P＞0.05）Between study and control groups, there was no significant difference in retinal morphology which was observed by light microscope at any stage of the study. By electron microscopic observation, retinal ultramicrostructure was no evident retinal toxicity being tested both at group A and B (1.25 mg/0.05 ml and 2.5 mg/0.1 ml). But at group C (6.25 mg/0.25 ml), significant mitochondrial swelling and hydropic changes were seen in the inner segments of photoreceptors. And there was no improvement of the pathological changes in four weeks. Conclusion It is safe that intravitreal injection of Avastin in rabbitprime;s eyes at dose 1.25 mg or 2.5 mg at single time. （Chin J Ocul Fundus Dis，2008，24：193-196）
ObjectiveTo compare the visual outcomes of treatment with intravitreal ranibizumab alone or in combination with photodynamic therapy (PDT) in patients with polypoidal choroidal vasculopathy (PCV). MethodsIn this retrospective and comparative study, 36 eyes of 36 patients with PCV were enrolled. Eighteen eyes received 0.5 mg (0.05 ml) ranibizumab injection only (simple injection group) and the other 18 eyes underwent combination therapy of ranibizumab injection and PDT (combination treatment group). Intravitreal ranibizumab was given at the third day after PDT. Re-treatment was considered in clinic examination. The minimum re-treatment interval was 3 months for combination therapy and 1 month for ranibizumab. Best corrected visual acuity (BCVA) of logarithm of the minimum angle of resolution (logMAR) at baseline and each follow-up visit at 1, 3, 6, 12 month was measured as a primary outcome, and complications also observed in every follow-up. ResultsNo complications occurred in these 36 patients during the treatment or follow-up, such as retinal detachment, sustained high intraocular pressure, retinal holes, intraocular inflammation, and systemic adverse reactions. The average times of ranibizumab injections of simple injection group and combined treatment group were (3.00±0.84) and (1.89±0.68) times respective, and the difference was significant (t=4.370, P=0.000). The logMAR BCVA of the first and third month after initial treatment between two groups were significant different (t=0.668, 0.940; P>0.05). However, there was no significant difference between them at the 6th and 12th month (t=2.188, 2.547; P<0.05). In the last follow-up, the logMAR BCVA were improved in simple injection group and combination treatment group compared to the pre-treatment values (t=3.351, 9.408; P=0.012, 0.000). In simple injection group, visual acuity was improved in 3 eyes (16.7%), stable in 13 eyes (72.2%) and decreased in 2 eyes (11.1%). In combination treatment group, visual acuity was improved in 4 eyes (22.2%), stable in 13 eyes (72.2%) and decreased in 1 eyes (5.6%). ConclusionsIntravitreal ranibizumab injection and combined with PDT are both effective to improve vision in patients with PCV. Visual acuity was the same between the two treatments in 3 months after initial treatment; however 6 to 12 months after first treatment, patients received PDT combined with intravitreal ranibizumab injection had better visual acuity than those received the intravitreal ranibizumab injection only.
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.
In the expert consensus published by the Pediatrics in 2013, it was first proposed that anti-VEGF drugs can be considered for retinopathy of prematurity (ROP) with stage 3, zone Ⅰ with plus disease. However, there are many problems worth the attention of ophthalmologists, including the advantages and disadvantages of anti-VEGF therapy compared with traditional laser therapy, systemic and ocular complications after anti-VEGF therapy, and what indicators are the end points of anti-VEGF therapy. Combined with this consensus and numerous research findings, we recommend that the first treatment for anti-VEGF or laser therapy should be considered from disease control effects. For the threshold and pre-threshold lesions, the effect of anti-VEGF therapy for zoneⅡ lesions is better than that for zone Ⅰ lesions and the single-time effective rate is high. So, it is suggested that anti-VEGF therapy should be preferred for the first treatment. The choice of repeat treatment should be considered from the final retinal structure and functional prognosis. Laser therapy is advisable for the abnormal vascular regression slower and abnormalities in the posterior pole. It can reduce the number of reexaminations and prolong the interval between re-examinations. However, the premature use of laser has an inevitable effect on peripheral vision field. Excluding the above problems, supplemental therapy can still choose anti-VEGF therapy again. Most of the children with twice anti-VEGF therapy are sufficient to control the disease. Anti-VEGF therapy should be terminated when there are signs such as plus regression, threshold or pre-threshold lesions controlled without recurrence, peripheral vascularization, etc.
PURPOSE:To verify existance of a-,~-,and 3'-protein kinase C(PKC)subspecies and their localization in rabbit retina. METHODS: Using an immunohistoehemical technique with mono- elonal antibodies against PKC isozymes- I (a),-I[ (13),and -~[ (Y) to characterize the distribution of PKC in rabbit retina. RESULTS:There is a positive immunostaining for a-,13-,and ~-PKC in rabbit retina. The immunoreactivity of a-PKC was observed mainly in the bipolar cells of inner nuclear layer and the outer segments of photorecptors. The positive immunostaining of 13-PKC could be seen in the ganglion cells,inner plexiform layer,inner nuclear layer,and the outer segments of photoreceptors. A diffuse and weak staining of Y-PKC is recognized in the ganglion cell layer,inner plexifrom layer,inner nuclear layer, and the outer segments of photoreceptors. CONCLUSION:The protein kinase C sub- speeies-a,-~,and-'Y are present in retina which is a part of the central nervous system
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.
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 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.
ObjectiveTo compare the one year efficacy of intravitreal injection with ranibizumb for macular edema (ME) secondary to ischemic and non-ischemic central retinal vein occlusion (CRVO).MethodsA total of 88 patients (88 eyes) with ME secondary to CRVO were enrolled in this retrospective study. The best corrected visual acuity (BCVA) was detected by the Early Treatment Diabetic Retinopathy Study Chart. The optical coherence tomography was used to measure the foveal retinal thickness (CRT) and macular edema volume. The patients were divided into non-ischemic group and ischemic group, 44 eyes of 44 patients in each group. There was no significant differences in age (t=0.650, P=0.517) and gender (χ2=0.436, P=0.509) between the two groups. Compared with the ischemic group, the CRT was significantly decreased in the non-ischemic group (t=−2.291, P=0.024), and the edema volume in the macular area was significantly reduced (t=−2.342, P=0.022). All eyes were treated with continuous intravitreal injection of ranibizumab three times, and repeated injections were performed as needed. The patients without obvious ME regression after treatment were combined with triamcinolone acetonide injection. The patients with peripheral retinal non-perfusion area were combined with peripheral retinal laser photocoagulation. The follow-up was 1 year. The number of injections was counted. The changes of BCVA, CRT and edema volume in the macular area were compared between the two groups.ResultsDuring the 1-year follow-up period, 88 eyes were injected 1 to 10 times, with the mean of 4.51±2.33. The number of injections in the ischemic group and non-ischemic group were 4.55±1.59 and 4.48±2.91, respectively. There was no significant difference in the average number of injections between the two groups (t=0.136, P=0.892). The number of acetonide injections and laser treatment in the ischemic group was significantly higher than that in the non-ischemic group (t=3.729, 9.512; P＜0.001). At the last follow-up, compared with the ischemic group, the BCVA was increased (t=8.128), the CRT was decreased (t=−7.029) and the edema volume in the macular area was decreased (t=−7.213) in the non-ischemic group (P＜0.001).ConclusionCompared with ME secondary to ischemic CRVO, intravitreal injection of ranibizumab for ME secondary to non-ischemic CRVO has the better outcome of vision improvement and edema regression as well as less frequent of acetonide injections and laser treatment.