The therapeutic effect of anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (nAMD) was determined by a number of factors. Comprehensive thorough analysis of clinical features, imaging results and treatment response can predict the potential efficacy and possible vision recovery for the patient, and also can optimize the treatment regime to make a personalized therapy plan. Precise medicine with data from genomics, proteomics and metabolomics study will provide more objective and accurate biology basis for individual precise treatment. The future research should focus on comprehensive assessment of factors affecting the efficacy of anti-VEGF therapy, to achieve individualized precise diagnosis and treatment, to improve the therapeutic outcome of nAMD.
Since anti-vascular endothelial growth factor (VEGF) therapy has recently become the first-line treatment of wet age related macular degeneration in China, as well as retinopathy of prematurity, neovascular glaucoma and macular edema secondary to diabetic retinopathy or retinal vein occlusion in other countries. It is worth thinking about that how to perform anti-VEGF treatment properly to benefit more patients. We reviewed the fields of clinical researches to explore the best role of anti-VEGF treatment in prevention and treatment of retinal disease in future.
ObjectiveTo assess the efficacy and safety of intravitreal aflibercept injection (IAI) compared with photodynamic therapy (PDT) in the treatment of Chinese patients with predominantly classic subfoveal choroidal neovascularization (CNV) lesions secondary to neovascular age-related macular degeneration (nAMD).MethodsA randomized, double-blind, multi-center phase-3 clinical trial lasting for 52 weeks (from December 2011 to August 2014). Subjects were randomized in a 3:1 ratio to either IAI group or PDT-to-IAI group. Subjects in the IAI group received 2 mg IAI at baseline and at week 4, 8, 16, 24, 32, 40, 48, with sham injection at week 28, 36. Subjects in the PDT-to-IAI group were forced to receive PDT once at baseline and more time at week 12, 24 if PDT retreatment conditions were met. Sham injections were given in PDT-to-IAI group at baseline and at week 4, 8, 16 and 24, followed by 2 mg IAI at week 28, 32, 36, 40, 48. The primary outcome of efficacy were the change in mean Best Corrected Visual Acuity (BCVA) from baseline to week 28, and that of week 52. Safety evaluation included the percentage of subjects who suffered treatment emergent adverse events (TEAEs).ResultsAmong the 304 subjects enrolled, there were 228 and 76 cases in IAI group and PDT-to-IAI group respectively. At week 28, the changes of mean BCVA in IAI group, PDT-to-IAI group compared to baseline were +14.0, +3.9 letters, respectively. At week 52, the changes of mean BCVA in two groups were +15.2, +8.9 letters respectively with the difference of +6.2 letters (95%CI 2.6−9.9, P=0.000 9). At week 52, the mean foveal retinal thickness in the two groups decreased by −189.6, −170.0 μm, respectively. Subjects with the most BCVA increase in IAI group were those aged ＜65, and those with active CNV lesion area ＜50% of total lesion area. The most common TEAEs in IAI group and PDT-to-IAI group are macular fibrosis [11.8% (27/228), 6.6% (5/76)] and BCVA decline [6.6% (15/228), 21.1% (16/76)]. There were 3 cases of arterial thromboembolic events defined in the antiplatelet experimental collaboration group, but all were considered unrelated to interventions.ConclusionsThe efficacy of aflibercept is superior to that of PDT in nAMD patients in China. The therapeutic effect of aflibercept persisted to week 52 in all subjects. The rate of adverse events was consistent with the safety data of aflibercept known before.
ObjectiveTo observe the effect of preoperative intravitreal ranibizumab injection (IVR) on the operation duration of vitrectomy and postoperative vision for the treatment of proliferative diabetic retinopathy (PDR). MethodsA prospective study was carried out with the 90 PDR patients (90 eyes) who underwent vitrectomy. The 90 patients(90 eyes)were assigned to the vitrectomy only group(43 eyes) and the IVR combined with vitrectomy group (47 eyes). The IVR was performed 5-13 days prior to vitrectomy in the IVR combined with vitrectomy group. There were 15 eyes with fibrous proliferation PDR (FPDR), 16 eyes with advanced PDR (APDR) without involving the macular and 16 eyes with APDR involving the macular in the vitrectomy only group. There were 14 eyes with FPDR, 15 eyes with APDR without involving the macular and 14 eyes with APDR involving the macular patients in the IVR combined with vitrectomy group. All the eyes in the two groups were regularly operated by the same doctor to complete the vitrectomy. The start and end time of vitrectomy were recorded. The average follow-up time was 10 months. The changes of best corrected visual acuity (BCVA) before and 1, 3 and 6 months after surgery were compared between the two groups. ResultsThe duration of operation of the FPDR type (t=-8.300) and the APDR involving the macular type (t=-2.418) in the IVR combined with vitrectomy group was shorter than vitrectomy only group (P < 0.05). The comparison of duration of operation of the APDR without involving the macular type in the two groups has no statistically significant difference (t=-1.685, P > 0.05). At 1 month after surgery, the comparison of BCVA of the IVR combined vitrectomy group and the vitrectomy only group in APDR involving the macular type has no statistically significant difference (t=0.126, P > 0.05). At 3, 6 months after surgery, the BCVA of the IVR combined vitrectomy group in APDR involving the macular type was significantly better than the BCVA of the vitrectomy only group (t=8.014, 7.808; P < 0.05). At 1, 3, and 6 months after surgery, the BCVA of the IVR combined vitrectomy group in FPDR type (t=3.809, 1.831, 0.600) and APDR without involving the macular type (t=0.003, 1.092, 3.931) compared with pre-treatment, the difference were not statistically significant (P > 0.05); the BCVA in APDR without involving the macular type compared with pre-treatment, the difference was distinctly statistically significant (t=2.940, 4.162, 6.446; P < 0.05); the BCVA in APDR involving the macular type (t=0.953, 1.682, 1.835) compared with pre-treatment, the difference were not statistically significant (P > 0.05). ConclusionPreoperative IVR of PDR can shorten the operation duration and improve the BCVA of APDR involving the macular type.
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 visual acuity change in patients with different patterns of optical coherence tomography (OCT) of diabetic macular edema (DME) after intravitreal ranibizumab injection and/or laser photocoagulation. Methods A retrospective observational case series. Seventy patients (99 eyes) with DME were enrolled. Best-corrected visual acuity (BCVA) was evaluated using the international vision test chart, and then convert the result to the logarithm of the minimum angle of resolution (logMAR). According to the morphological characteristics of OCT, the DME was divided into 3 patterns, including diffuse macular edema (DRT), cystoid macular edema (CME) and serous neuroepithelial layer detachment. The average follow-up was (80.43±74.89) days. The patients were divided into 3 groups according to the different treatments, including intravitreal ranibizumab injection group (group A, 21 patients, 25 eyes), intravitreal ranibizumab injection and laser photocoagulation group (group B, 23 patients, 26 eyes), laser photocoagulation group (group C, 26 patients, 48 eyes). The changes of absolute BCVA (ABCVA) and improved visual acuity were compared between different treatment groups and different OCT patterns. ABCVA = logMAR BCVA before treatment－logMAR BCVA after treatment. Improvement more than 0.3 of logMAR value was considered as improved visual acuity. Results There was no significant difference in ABCVA between different treatment groups (F=0.050,P＞0.05). The improved visual acuity in group A and B were great than group C (χ2=5.645, 6.301;P＜0.05). In group A, B and C, there was no significant difference in ABCVA and improved visual acuity between different OCT patterns (P＞0.05). Improved visual acuity of DRT and CME eyes were higher in group A&B (70.59% and 50.00%) than in group C (26.47% and 14.29%), the difference was statistically significant (χ2=5.075, 4.453;P＜0.05). Conclusions There is no obvious change of visual acuity in patients with different OCT patterns of DME after the same treatment by intravitreal ranibizumab injection and/or laser photocoagulation. The improved visual acuity is not consistent in same OCT patterns after different treatment.
ObjectiveTo observe the efficacy and safety of combination of intravitreal injection of ranibizumab and laser photocoagulation for the treatment of aggressive posterior retinopathy of prematurity (AP-ROP). MethodsMedical records of 70 eyes of 35 premature infants with a primary diagnosis of AP-ROP in our clinic were reviewed and analyzed retrospectively. All the lesions were located in posterior zone, with 42 eyes in zone 1 and 28 eyes in zone 2. Forty-six eyes had iris neovascularization, while 19 eyes combined with vitreous hemorrhage. All participants underwent intravitreal injection of ranibizumab as the primary treatment within 12 hours after diagnosis of AP-ROP. The systemic and ocular adverse effects were observed. The change of retinal vascular tortuosity and dilatation before and after the intravitreal injection of ranibizumab was observed one week after injection. Laser photocoagulation was used as adjuvant therapy if the plus disease persisted more than two weeks or new-onset ridge occurred after injection. The mean time interval between injection and laser therapy was (5.1±2.6) weeks (range, 1-10 weeks). Follow-up ranged from 6 to 18 months, with a mean of (10.3±3.9) months. The anatomical results and complications were evaluated after treatment. The eyes that progressed to stage 4 or 5 during the follow-ups were underwent lens-sparing vitrectomy or lensectomy combined with vitrectomy. ResultsNo major systemic or ocular complications were observed. Preretinal hemorrhages were found in 12 eyes of 8 patients (17.1%), but they were absorbed spontaneously during the follow-ups. All lens remained transparent and no iatrogenic retinal hole was occurred during the follow-ups. After the injection, the regression of iris neovascularization was observed in 46 eyes within one week, vitreous hemorrhage absorbed significantly in 16 eyes (84.2%), and plus disease disappeared completely within one week in 61 eyes (87.1%). 59 eyes (84.3%) demonstrated vascularization toward the peripheral retina after treatment. 32 out of 42 eyes (76.2%) with zone 1 demonstrated vascularization toward to zone 2, while 24 out of 28 eyes (85.7%) with zone 2 demonstrated vascularization toward to the junction of zone 2 and 3. After intravitreal injection of ranibizumab combined with laser photocoagulation, 62 of 70 eyes (88.6%) had retinal vascular ridge and plus disease regression. However, 8 eyes of 6 patients (11.4%) showed significant fibrovascular proliferation and progressed to retinal detachment after the combination treatment of intravitreal ranibizumab injection and laser photocoagulation. Four eyes underwent lens-sparing vitrectomy, while the other 4 eyes underwent vitrectomy combined with lensectomy. Five eyes achieved totally retinal reattachment after surgery, while 3 eyes achieved partially retinal reattachment. ConclusionThe combination of intravitreal injection of ranibizumab and laser photocoagulation is safe and effective in the treatment of AP-ROP.
Choroidal neovascularization (CNV) is the key characteristic of neovascular age-related macular degeneration (nAMD), and the effective therapy is intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents based on clinical and basic research. In the meantime the challenge is how to further improve the inhibiting effect for CNV and visual function of anti-VEGF treatment on nAMD. The new strategy and drug delivery devices for anti-VEGF treatment will optimize the clinical scheme. From bench to bedside, the research on targeted treatment of angiogenesis brings the bloom of nAMD medical therapy.
ObjectiveTo systematically review the efficacy and safety of photodynamic therapy (PDT) and intravitreal vascular endothelial growth factor (VEGF) inhibitors in the treatment of polypoidal choroidal vasculopathy (PCV), and to investigate the primary treatment tentatively. MethodsA systematic search of Pubmed, Embase, the Cochrane Library and the Wanfang Data was performed to identify all comparative studies that compared the outcomes of PDT alone, intravitreal VEGF inhibitors alone and combined intravitreal VEGF inhibitors and photodynamic therapy. Outcomes of interest included the regression and recurrence rate of polypoidal lesions, best corrected visual acuity (BCVA), central retinal thickness (CRT), therapeutic times, and the occurrence rate of adverse events. 2 randomized controlled trials (RCT) and 19 non-RTCs were identified. According to treatment methods, the data extracted was classified to 3 groups, analyzed with odds ratio (OR), weighted mean difference (WMD) and 95%confidence interval (95%CI). ResultsMeta-analysis suggests that the regression rate of polypoidal lesions (OR=0.34, 0.07; 95%CI=0.13-0.88, 0.02-0.36) and BCVA (WMD=0.25, 0.11; 95%CI=0.14-0.36, 0.01-0.21) in combined therapy group were significantly better than those in PDT group and intravitreal VEGF inhibitors group (P < 0.05). The recurrence rate of polypoidal lesions in PDT group was significantly lower than intravitreal VEGF inhibitors group (OR=0.35, 95%CI=0.16-0.74, P=0.006). BCVA (P=0.025) and the occurrence rate of adverse events (OR=60.36, 95%CI=6.04-603.50, P=0.000 5) in intravitreal VEGF inhibitors group were significant better than PDT group. ConclusionsCombined treatment appeared to be superior to PDT alone or intravitreal VEGF inhibitors alone. Combined treatment takes priority over all others in the primary treatment of PCV.
Diabetic macular ischemia (DMI) is one of the manifestation of diabetic retinopathy (DR). It could be associated with diabetic macular edema (DME), which may affect the vision of DR patients. FFA is the gold standard for the diagnosis of DMI, but with the advent of OCT angiography, a more convenient and diversified method for the evaluation of DMI has been developed, which makes more and more researchers start to study DMI. Intravitreal injection of anti-VEGF has become the preferred treatment for DME. When treating with DME patients, ophthalmologists usually avoid DMI patients. But if intravitreal anti-VEGF should be the contradiction of DME is still unclear. To provide references to the research, this article summarized the risk factors, assessment methods and influence of DMI. This article also analyzed the existing studies, aiming to offer evidences to a more reasonable and effective treatment decision for DME individual.