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.
Exudative or wet age-related macular degeneration (AMD) is characterized by the progressive growth of choroidal neovascularization (CNV). Anti-vascular endothelial growth factor (VEGF) drugs have been used in the control of the development of CNV and vision improvement, but there are still defects like frequent injections, drug resistance and so on. Radiotherapy can deactivate local inflammatory cell populations, and make CNV unstable in the absence of pericytes and VEGF stimulation, which induce apoptosis of the vascular endothelial cells. Therefore, radiotherapy is considered as a potential adjuvant treatment of anti-VEGF therapy. The current clinical approaches include epimacular brachytherapy (EMBT) and long-range stereotactic radiotherapy (SRT). SRT may be a preferred adjuvant treatment for patients receiving anti-VEGF therapy. Knowing the progress of radiotherapy for the treatment of exudative AMD may help us to fully understand the pathogenesis of wAMD in China
Evidence-based guidelines for diagnosis and treatment of diabetic retinopathy in China (2022) is based on evidences in recent clinical trials and a system of Grading of Recommendations, Assessment, Development and Evaluation of evidence quality and strength of recommendations. The main key points around why the diabetic macular edema (DME) changes the classification, what thresholds for initiating anti-vascular endothelial growth factor (VEGF) drug therapy; eyes with center-involved DME (CI-DME) and good vision for clinical significant macular edema still treated by focal laser even with good vision, the clinical pathway for CI-DME changes first-line treatment from laser to anti-VEGF, loading dose of anti-VEGF for CI-DME in non-proliferative diabetic retinopathy (DR) from 3 injections up to 4-5 injections is recommended; severe non-proliferative DR and proliferative DR with vision impairment but without hemorrhages and retinal traction could be considered first treatment of anti-VEGF comparing to initiate pan-retinal photocoagulation (PRP) (weakly recommended), PRP is still gold-standard for progressive non-perfusion area of retina. With the rapid development of DR evaluation devices such as optical coherence tomography, wide-angle optical coherence tomography angiography and wide-angle fluorescein fundus angiography, imaging biomarkers have been provided for the degree of DR lesion, treatment response and prognosis. It is believed that the clinical practice will be promoted a new height by the 2022 edition of Chinese DR guideline.
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 evaluate the macular visual function of patients with myopic choroidal neovascularization (MCNV) before and after intravitreal injection of conbercept.MethodsA prospective, uncontrolled and non-randomized study. From April 2017 to April 2018, 21 eyes of 21 patients diagnosed as MCNV in Shanxi Eye Hospital and treated with intravitreal injection of conbercept were included in this study. There were 9 males (9 eyes, 42.86%) and 12 females (12 eyes, 57.14%), with the mean age of 35.1±13.2 years. The mean diopter was −11.30±2.35 D and the mean axial length was 28.93±5.68 mm. All patients were treated with intravitreal injection of conbercept 0.05 ml (1+PRN). Regular follow-up was performed before and after treatment, and BCVA and MAIA micro-field examination were performed at each follow-up. BCVA, macular integrity index (MI), mean sensitivity (MS) and fixation status changes before and after treatment were comparatively analyzed. The fixation status was divided into three types: stable fixation, relatively unstable fixation, and unstable fixation. The paired-sample t-test was used to compare BCVA, MI and MS before and after treatment. The x2 test was used to compare the fixation status before and after treatment.ResultsDuring the observation period, the average number of injections was 3.5. The logMAR BCVA of the eyes before treatment and at 1, 3, and 6 months after treatment were 0.87±0.32, 0.68±0.23, 0.52±0.17, and 0.61±0.57, respectively; MI were 89.38±21.34, 88.87±17.91, 70.59±30.02, and 86.76±15.09, respectively; MS were 15.32±7.19, 21.35±8.89, 23.98±11.12, 22.32±9.04 dB, respectively. Compared with before treatment, BCVA (t=15.32, 18.65, 17.38; P＜0.01) and MS (t=4.08, 3.50, 4.26; P＜0.01) were significantly increased in the eyes 1, 3, and 6 months after treatment. There was no significant difference in the MI of the eyes before treatment and at 1, 3, and 6 months after treatment (t=0.60, 2.42, 2.58; P＞0.05). Before treatment and at 1, 3, and 6 months after treatment, the proportion of stable fixation were 28.57%, 38.10%, 38.10%, 33.33%;the proportion of relatively unstable fixation were 47.62%, 47.62%, 52.38%, 57.14% and the proportion of unstable fixation were 23.81%, 14.28%, 9.52%, 9.52%, respectively. The proportion of stable fixation and relatively unstable fixation at 1, 3 and 6 months after treatment were higher than that before treatment, but the difference was not statistically significant (x2=1.82, 1.24, 1.69; P＞0.05).ConclusionBCVA and MS are significantly increased in patients with MCNV after intravitreal injection of conbercept.
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.
According to the best corrected visual acuity and the morphological changes of the macular fovea, responses to the neovascular age-related macular degeneration (nAMD) who receive anti-vascular endothelial growth factor (VEGF) therapy show large variability, including poor and non-responders. Various factors will be reviewed to account for poor and non-response to anti-VEGF therapy, such as the related susceptibility genes, factors related with the development of choroidal neovascularization and morphologic parameters, pharmacokinetics and tachyphylaxis. The future research should focus on comprehensive assessment of factors affecting the efficacy of anti-VEGF therapy to improve the therapeutic outcome of nAMD.
Objective To study and compare the clinical efficacy between intravitreal conbercept injection and (or) macular grid pattern photocoagulation in treating macular edema secondary to non-ischemic branch retinal vein occlusion (BRVO). Methods Ninety eyes of 90 patients diagnosed as macular edema secondary to non-ischemic BRVO were enrolled in this study. Forty-eight patients (48 eyes) were male and 42 patients (42 eyes) were female. The average age was (51.25±12.24) years and the course was 5–17 days. All patients were given best corrected visual acuity (BCVA), intraocular pressure, slit lamp with preset lens, fluorescence fundus angiography (FFA) and optic coherent tomography (OCT) examination. The patients were divided into conbercept and laser group (group Ⅰ), laser group (group Ⅱ) and conbercept group (group Ⅲ), with 30 eyes in each group. The BCVA and central macular thickness (CMT) in the three groups at baseline were statistically no difference (F=0.072, 0.286;P=0.930, 0.752). Patients in group Ⅰ received intravitreal injection of 0.05 ml of 10.00 mg/ml conbercept solution (conbercept 0.5 mg), and macular grid pattern photocoagulation 3 days later. Group Ⅱ patients were given macular grid pattern photocoagulation. Times of injection between group Ⅰ and Ⅲ, laser energy between group Ⅰ and Ⅱ, changes of BCVA and CMT among 3 groups at 1 week, 1 month, 3 months and 6 months after treatment were compared. Results Patients in group Ⅰ and Ⅲ had received conbercept injections (1.20±0.41) and (2.23±1.04) times respectively, and 6 eyes (group Ⅰ) and 22 eyes (group Ⅲ) received 2-4 times re-injections. The difference of injection times between two groups was significant (P＜0.001). Patients in group Ⅱ had received photocoagulation (1.43±0.63) times, 9 eyes had received twice photocoagulation and 2 eyes had received 3 times of photocoagulation. The average laser energy was (96.05±2.34) μV in group Ⅰ and (117.41±6.85) μV in group Ⅱ, the difference was statistical significant (P=0.003). BCVA improved in all three groups at last follow-up. However, the final visual acuity in group Ⅰ and group Ⅲ were better than in group Ⅱ (t=4.607, –4.603;P＜0.001) and there is no statistical significant difference between group Ⅲ and group Ⅰ (t=–0.802,P=0.429). The mean CMT reduced in all three groups after treating for 1 week and 1 month, comparing that before treatment (t=–11.855, –10.620, –10.254;P＜0.001). There was no statistical difference of CMT between group Ⅰand Ⅲ at each follow up (t=0.404, 1.723, –1.819, –1.755;P=0.689, 0.096, 0.079, 0.900). CMT reduction in group Ⅰ was more than that in group Ⅱ at 1 week and 1 month after treatments (t=–4.621, –3.230;P＜0.001, 0.003). The CMT in group Ⅲ at 3 month after treatment had increased slightly comparing that at 1 month, but the difference was not statistically significant (t=1.995,P=0.056). All patients had no treatment-related complications, such as endophthalmitis, rubeosis iridis and retinal detachment. Conclusions Intravitreal conbercept injection combined with macular grid pattern photocoagulation is better than macular grid pattern photocoagulation alone in treating macular edema secondary to non-ischemic BRVO. Combined therapy also reduced injection times comparing to treatment using conbercept injection without laser photocoagulation.
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.
ObjectiveTo observe the changes of macular blood flow density in patients of macular telangiectasis type 1 (Mac-Tel type 1) with macular edema before and after the treatment of anti-VEGF.MethodsA retrospective clinical study. From January 2016 to December 2017, 14 Mac-Tel type 1 patients (14 eyes) diagnosed in Nanjing Medical University Eye Hospital were included in the study. There were 6 males (6 eyes) and 8 females (8 eyes), with the mean age of 35.3±9.3 years. All patients underwent BCVA and OCT angiography examinations. The BCVA examination was performed using the Snellen visual acuity chart, which was converted into logMAR visual acuity. All the patients were received anti-VEGF injection treatment once a month for 3 consecutive months. The OCTA scanning region in the macular area was 3 mm × 3 mm. Macular blood flow density in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), the vessel density within a 300 μm width ring surrounding the foveal avascular area (FD-300) and central macular thickness (CMT) were measured in all eyes. Paired samples t-test and Pearson correlation analysis were used in this study.ResultsAt the baseline, logMAR BCVA was 0.69±0.07, CMT was 468.43±26.59 μm, SCP blood flow density was (50.99±1.19)%, DCP blood flow density was (43.79±1.44)%, FD-300 was (50.73±1.16)%. Compared with the baseline, there were significant differences between logMAR BCVA, CMT, DCP blood flow density and FD-300 in 1 week, 1 month, 3 months after treatment and 2 months after cessation of treatment (logMAR BCVA: t=6.77, 13.30, 16.99, 9.51; P=0.00, 0.01, 0.00, 0.01. CMT: t=6.99, 15.88, 26.10, 6.50; P=0.00, 0.01, 0.01, 0.00. DCP: t=6.75, 8.61, 15.12, 7.63; P=0.00, 0.01, 0.01, 0.00. FD-300: t=11.86, 13.08, 14.36, 4.41; P=0.00, 0.01, 0.01, 0.03). There was no significant difference in blood flow density of SCP between baseline and 2 months after cessation of treatment (t=1.36, P=0.19), but there was significant difference at the other time points after treatment (t=5.50, 6.84, 6.27; P=0.00, 0.01, 0.01). The Pearson's correlation analysis showed that there was a significant positive correlation between FD-300 and CMT (r2=0.54, P=0.04).ConclusionsThere is no significant change in the SCP blood flow density in the patients of Mac-Tel type 1 with macular edema, while the DCP blood flow density decreased and FD-300 increased. After anti-VEGF treatment, DCP blood flow density increased and FD-300 decreased. FD-300 is positively correlated with CMT.