Objective To observe the inhibitory effect of Bevacizumab on retinal neovascularization in oxygen-induced retinopathy in the mouse. Methods 90 one-week-old C57B L/6J mice were divided into four groups at random. 15 mice in the 1st group as normal control group, 15 mice in the 2nd group as oxygen control group, 30 mice in the 3rd group as high-dose Bevacizumab treatment group, 30 mice in the 4th group as low-dose Bevacizumab treatment group. The 2nd, 3rd and 4th groups were exposed to 75% oxygen for 5 days and then to room air. At the 12th day, One eye of each mouse of two control groups were received an intravitreal injection with Be vacizumab at 2 mu;l、1 mu;l respectively, and the same volume of BSS was injected into the other eye of the mice. The adenosine diphosphatase (ADPase) histochemical technique was used for retinal flat mount to assess the oxygen-induced change s of retinal vessels. The number of the endothelium cell nuclei of proliferative neovascularization was quantified by retinal microtome chromoscopy. Real-time PCR analysis was performed to examine the expression of VEGF mRNA. Results Comparing with oxygen control group, regular distributions, reduced density of retina l vascular and reduced endothelium cell nuclei which extending retinal membrane were observed in the treatment groups(P＜0.001). But the differences between two treatment groups are not statistically significant (P＞0.05). The expression of VEGF mRNA was not significantly different in oxygen control group whatever it whether accepted Bevacizumab treatment or high or low dose (P＞0.05). Conclusion Intravitreal injection with Bevacizumab can effectively inhibits the retinal neova scularization in oxygen-induced retinopathy in the mouse. Intravitreal injection with Bevacizumab might become to the new method to treat retinopathy of premature. （Chin J Ocul Fundus Dis，2008，24：184-188）
ObjectiveTo evaluate the effectiveness and complications associated with the use of ranibizumab in the treatment of ZoneⅠand ZoneⅡretinopathy of prematurity (ROP). MethodsData from patients of ROP who had received intravitreal ranibizumab (IVR) injections in Peking University People's Hospital for the treatment of ROP from July 2012 to December 2013 were collected. In total, 151 eyes from 85 patients (56 male and 29 female) were analyzed. The mean birth weight was (1438.6±334.5) g (range:790-2280 g), mean gestational age was (30.1±2.0) weeks (range:25-37 weeks), mean age at the time of intervention was (37.0±6.2) gestational weeks (range:32-45 weeks), mean follow-up was (4.9±3.3) months (range:1.4-20.8 months). The main outcome measures were the regression of ROP and the complications that were associated with the IVR injections. ResultsAfter receiving IVR injections, 120 eyes (79.5%) exhibited ROP regression after single injection. Twenty-six eyes (17.2%) required additional laser treatment for ROP regression after the absence of a positive response to the IVR injections. Five eyes (3%) progressed to stage 4 ROP and required vitrectomy to reattach the retinas. Fifty of 120 eyes which were regressed after single IVR had recurrence of ROP and need additional laser or additional IVR. All of the eyes (100.0%) had attached retinas after the various treatments that they received. No notable systemic complications related to the IVR injections were observed. ConclusionsIVR injection seems to be an effective and well-tolerated method to treat ZoneⅠand ZoneⅡROP. Recurrence of ROP is common and long-term follow up may be needed.
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.
ObjectiveTo observe the effect of intravitreal injection of conbercept in the treatment of retinopathy of premature (ROP) and to analyze the factors related to the therapy.MethodsA retrospective study. A total of 57 patients (57 eyes) with pre-threshold type 1 (30 patients, 30 eyes), threshold ROP (21 patients, 21 eyes) and acute aggressive posterior ROP (APROP, 6 patients, 6 eyes)) from premature infants by retinal screening in Henan Provincial People’s Hospital during October 2017 and June 2018 were enrolled in this study. All children were received routinely intravitreal injected 10 mg/ml conbercept 0.025 ml (0.25 mg) within 24 hours after diagnosis. Fundus examination was performed 7 days after injection. The interval of examination was 1−3 weeks according to fundus conditions. The mean follow-up was 30.1±4.6 weeks. For patients with relapse or no response to treatment, repeated intravitreal injection of conbercept or laser photocoagulation therapy was given. The retinal blood vessels of the affected eyes were observed. Logistic stepwise regression analysis was used for the correlation test of multiple factors.ResultsAmong 57 eyes, 49 eyes and 8 eyes were treated with 1 or 2 times of intravitreal injection of conbercept. After 24 weeks of treatment, in 57 eyes, 26 eyes were cured (45.6%), 22 eyes improved (38.6%), 8 eyes relapsed (14.0%), and 1 eye aggravated (1.8%). The recurrence time was 12.9±4.5 weeks after the first injection, and the corrected gestational age was 49.0±6.7 weeks. There were significant differences in initial injection time, lesion range among the cure, improved and recurrence eyes (F=5.124, 7.122; P＜0.01, ＜0.01). Parameters of ROP condition, including ROP diagnosis (pre-threshold type 1, threshold and APROP), zone (zone 1 and 2), stage (stage 2 and 3) and plus lesions, were significant different among the cure, improved and recurrence eyes (χ2=11.784, 14.100, 6.896, 9.935; P＜0.01, ＜0.01, ＜0.05, ＜0.01). Logistic stepwise regression analysis showed that the recurrence rate was correlated with ROP zone, more likely recurrence at zone 1 than zone 2 (Wald=9.879, OR=27.333, P=0.002). No injection-related complications such as endophthalmitis, cataract and glaucoma were found during treatment and follow-up period.ConclusionsIntravitreal injection of conbercept is effective in the treatment of ROP without obvious adverse reactions. Lesion zoning is associated with recurrence after treatment.
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.
Intravitreal injection of anti-VEGF drugs for the treatment of retinopathy of prematurity (ROP) is a hot topic of research, and it can be used to treat the ROP (Ⅰzone). The current anti-VEGF drugs include bevacizumab, ranibizumab, aflibercept and conbercept, etc. However, in recent years, several studies have confirmed that anti-VEGF drugs have an increased recurrence rate and a longer recurrence time than conventional laser photocoagulation therapy. The follow-up period should be extended and repeated injections may be required. Due to the lack of large-scale prospective clinical studies, the recurrence rate, time window of recurrence, risk factors and treatment methods of various anti-VEGF drugs for ROP are still unclear. Anti-VEGF drugs in the treatment of ROP needs to accumulate more evidence-based medical evidence.
ObjectiveTo evaluate the safety and efficacy of 27G micro-incision vitrectomy surgery (MIVS) combined with intravitreal injection of ranibizumab (IVR) in the treatment of retinopathy of prematurity (ROP) with early intervention failure.MethodsRetrospective case series was performed. Fourteen eyes (11 infants) with ROP who underwent 27G MIVS combined with IVR were included from March 2016 to January 2018 in Shenzhen Eye Hospital. Among them, there were 5 males with 7 eyes, 6 females with 7 eyes. The average gestational age of the infants was 28.12±0.90 weeks; the average birth weight was 1 023.64±200.96 g. Before the early clinical intervention, 1 infant (2 eyes) had ROP in zone Ⅰstage 3 with plus disease, 8 infants (10 eyes) had ROP in zone Ⅱ stage 3 with plus disease, and 2 infants had ROP in aggressive posterior ROP. Six eyes underwent laser photocoagulation, while 8 eyes received laser therapy combined with IVR. Six eyes of stage 4A ROP and 8 eyes in stage 4B. Retinal detachment was detected with a mean of 10.44±9.21 weeks. At the time of surgery, the average post-conceptional age was 48.02±8.09 weeks. All the affected eyes were treated with standard sclera with three incisions 27G MIVS. During the operation, only local vitrectomy was performed to release and clear fibroascular proliferation in the optic disc, anterior macular area and pericristal area. After surgery, 10 mg/ml of ranibizumab 0.03 ml was injected into the vitreous cavity. The average follow-up time was 23.36±8.34 months. The primary objectives were the condition of retinal reset, ROP progression control and complications.ResultsAll patients had uneventful surgeries with an average duration of 32.86±9.35 mins. Of the 14 eyes, 12 eyes (85.71%) were controlled, 8 eyes (57.14%) had a good rearrangement of macular structure, while 4 eyes with macular traction. Two eyes had ROP progression, recurrence of retinal detachment, posterior synechia. Complicated cataract was in 1 eye. Proliferative vitreoretinopathy and retinal detachment was in 1 eye after 7 months the operation.Conclusion27G MIVS combined with IVR is a safe and effective treatment for ROP with early clinical intervention failure.
ObjectiveTo observe the effect of intravitreal injection of Conbercept with two different doses in the treatment of retinopathy of prematurity (ROP）and explore the clinical feasibility of ROP treatment by lower dose conbercept.MethodsThis was a prospective study. The premature infants were enrolled with pre-threshold type 1, threshold and acute aggressive posterior retinopathy of prematurity (AP-ROP) from March 2018 to June 2019, who received fundus screening in neonatal intensive care unit (NICU) of Henan Provincial People's Hospital, Henan Eye Hospital. They were randomly divided into two groups. The group A (lower dose group) were received intravitreal injection of conbercept with 0.15 mg/0.015 ml, and those in group B (control group) were received intravitreal injection of conbercept with 0.25 mg/0.025 ml. We checked and recorded the lesion area, stage, scope (according to the clock range), additional lesion (plus), etc. Fundus examination should be performed with the pediatric wide-field fundus imaging system within 7 days after treatment. It was used to observe the plus disese, ridge, regression of neovascularization on ridge, and development of retinal vessels to serrated edge or scarring. The follow-up period was at least 24 weeks. The effect evaluation was divided into recovery, improvement, recurrence and aggravation.ResultsThe 43 ROP subjects (84 eyes) were enrolled including 21 cases (40 eyes) in group A and 22 (44 eyes) in group B. There was no significant difference between the two groups in gender (χ2=1.169), birth age (t=0.283), birth weight (t=0.547), hospitalization days in NICU (t=1.187), first examination time (t=1.811), first injection time (t=0.492), follow-up time (t=0.899) and ROP condition (χ2=0.854) (P>0.05). In group A, 21 eyes (52.5%) were cured, 17 eyes (42.5%) were improved, 2 eyes (5.0%) were recurred, and no aggravating cases were found. In group B, 24 eyes (54.5%) were cured, 14 eyes (31.8%) were improved, 6 eyes (13.6%) were recurred, and no aggravating cases were found. There was no significant difference of the cure rate (χ2=2.210, P>0.05) and effective (recovery and improvement) rate (χ2=1.814, P=0.269）between two groups after the first injection.ConclusionIntravitreal injection of conbercept with the two doses should be effective in the treatment of ROP.