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.
ObjectiveTo observe the changes of macular microvascular structure in eyes with macular edema secondary to branch retinal vein occlusion (BRVO-ME) after intravitreal injection of conbercept and analyze its relationship with visual function and central retinal thickness (CRT).MethodsA prospective clinical study. From July 2018 to June 2019, 21 eyes of 21 patients with unilateral temporal BRVO-ME diagnosed in the Department of Ophthalmology of Peking Union Medical College Hospital were included in the study. Among them, there were 14 eyes of 14 males and 7 eyes of 7 females; the average age was 58.0±8.3 years. There were 13 eyes and 8 eyes with occlusion of the superior temporal and inferior temporal branches of the retinal vein, respectively. The affected area was defined as the side of the venous obstruction. All the affected eyes underwent best-corrected visual acuity (BCVA) and optical coherence tomography angiography (OCTA) examination. The BCVA was tested using the international standard logarithmic visual acuity chart, which was converted into the logarithmic minimum angle of resolution (logMAR) visual acuity during statistical analysis. All the eyes were treated with intravitreal injection of conbercept once a month for 3 months, and then treated as needed. A 3 mm × 3 mm scan centered on fovea was obtained and the vascular density of superficial capillary plexus (SCP) and deep capillary plexus (DCP), fovea avascular zone (FAZ) area, perimeter of FAZ (PERIM), acircularity index (AI), foveal vascular density in a 300 μm wide region around FAZ (FD-300) and central retinal thickness (CRT) were measured. The follow-up time after treatment was 6 months. The vascular density and FAZ parameters were compared before and after treatment by paired t test. The correlations of BCVA, CRT and vascular density, FAZ area and the other parameters at 6 months after treatment were analyzed by linear regression analysis. ResultsBefore treatment, the logMAR BCVA of the eyes was 0.506±0.159, and the CRT was 375.4±81.3 μm; 6 months after treatment, the logMAR BCVA of the eyes was 0.294±0.097, and the CRT was 266.3±46.7 μm. There was a statistically significant difference of logMAR BCVA and CRT between the eyes before and after treatment (t=8.503, 9.843; P＜0.05). There was no statistically significant difference in the overall vascular density of SCP and DCP before and 6 months after treatment (t=－0.091, －0.320; P＞0.05). The foveal vascular density decreased, and the difference was statistically significant (t=8.801, 3.936; P＜0.05). The vascular density of DCP of the affected area increased, and the difference was statistically significant (t=－2.198, P＜0.05). Compared with those before treatment, the FAZ area and PERIM of the affected eyes had an increasing trend, while AI and FD-300 had a decreasing trend, and the differences were statistically significant (t=－18.071, －12.835, 2.555, 8.610; P＜0.05). The linear regression analysis showed that BCVA and FAZ area 6 months after treatment have significant correlation (t=2.532, P=0.024). ConclusionCRT decreased and BCVA increased after intravitreal injection of conbercept in BRVO-ME eyes. After treatment, the foveal vascular density of SCP and DCP decreased while the vascular density of DCP of the affected area increased. The FAZ increased and the PERIM and AI decreased during follow-up. The BCVA was significantly correlated with the FAZ area 6 months after treatment.
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.
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 observe the clinical characteristics and therapeutic effect of reactivation of retinopathy of prematurity (ROP) patients after intravitreal injection of ranibizumab (IVR). MethodsA retrospective case series study. Eleven children with ROP (21 eyes) who were reactivated after IVR in Shenzhen Eye Hospital from January 2019 to October 2021 were included in the study. Among them, there were 6 males (11 eyes) and 5 females (10 eyes), with the gestational age of (27.6±2.2) weeks and birth weight of (1 034.6±306.5) g. At the first IVR treatment, 14 eyes (63.7%, 14/22) had acute ROP (AROP), 8 eyes (36.3%, 8/22) had threshold lesions. Post-reactivation treatments include IVR, retinal laser photocoagulation (LP), or minimally invasive vitrectomy (MIVS). The follow-up time after treatment was 12 to 18 months. Birth gestational age, birth weight, treatment method, corrected gestational age at treatment, lesion stage before and after treatment, lesion reactivation and regression time were recorded. The clinical characteristics and efficacy were observed and analyzed. ResultsThe time from initial IVR treatment to reactivation was (8.2±3.5) weeks. The corrected gestational age of the child was (43.62±4.08) weeks. In 21 eyes, AROP, threshold lesion, pre-threshold lesion, and stage 4 lesion were in 2, 4, 12, and 3 eyes, respectively. The patients were treated with IVR, LP, IVR+LP, IVR+MIVS in 2, 13, 4 and 2 eyes, respectively. After the first reactivation treatment, the time of regression and stability was (8.4±4.9) weeks after treatment. There were 5 eyes with secondary reactivation of the lesion, and the lesion stages were stage 3, stage 4a and stage 5 in 2, 1 and 2 eyes, respectively. The mean reactivation time was (19.3±6.0) weeks after the last treatment. The patients in stage 3, stage 4a and stage 5 were treated with LP, LP+MIVS and IVR, respecitively, and the lesions subsided steadily during follow-up. At the last follow-up, 19 out of 21 eyes showed complete regression of the lesions, stable photocoagulation, regression of crista-like lesions, no additional lesions, and retinal leveling. All retinal detachment was "funnel-shaped" in 2 eyes. ConclusionsThe lesion reactivation of AROP after IVR treatment is more common. The early reactivation rate is higher after treatment. There is a possibility of reactivation twice after re-treatment.
Objective To explore the inhibitory effects of r-k4k5 on retinal neovascularization. Methods Eighty-eight one-week-old C57BL/6J mice were put into the environment with 75% oxygen for 5 days to establish models of vascular proliferation retinopathy. One eye of each mouse received an intravitreal injection of 500 ng of r-k4k5 (large-dosage group) and of 250 ng of r-k4k5(small-dosage group), and the same volume of BSS was injected into the other eye of the mice both in these two groups as a control. The ADPase histochemical staining was used for retinal flatmount to observe changes of retinal vessels. The inhibitory effects of r-k4k5 on retinal neovascularization were evaluated by counting the endotheliocyte nuclei of new vessels extending from retina to vitreous in the tissue-slice. Results Regular distributions and reduced density of retinal blood vessels in eyes in the treatment group were found in retinal flatmount. The number of the endotheliocyte nuclei of new vessels extending from retina to vitreous was less in the eyes in the treatment group than which in control group (Plt;0.001). The nuclei of new blood vessels in the large-dosage group were less than which in small-dosage group (Plt;0.001). No histologic evidence of retinal toxicity or inflammatory response was found in the tissue-slice after the injection of r-k4k5. Conclusions Retinal neovascularization can be inhibited by intravitreal injection of r-k4k5,which suggests that intravitreal injection of r-k4k5 may have potential therapeutic benifits in retinal vascular disease. (Chin J Ocul Fundus Dis，2003，19：121-124)
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 conduct a systematic review of clinical manifestations, treatment, and associated genotyping of Sorsby fundus dystrophy (SFD). MethodsAn evidence-based medicine study. Sorsby fundus dystrophy, anti-vascular endothelial growth factor therapy, choroidal neovascularization, macular neovascularization, and TIMP3 gene were hereby used as search terms. Relevant literature was searched in CNKI, Wanfang, PubMed of the National Library of Medicine, and Embase of the Netherlands. The time span for literature searching ranged from the establishment of the database to April 2022, and two reviewers independently screened the literature and extracted relevant data, with duplicates, incomplete or irrelevant articles, and review articles excluded. SPSS26.0 software was used for analysis. The 95% confidence interval (CI) was used as an estimate of the effect size. The clinical manifestations, treatment and related pathogenic genes of SFD were counted and recorded. ResultsAccording to the search strategy, 157 pieces of literature were initially retrieved, and 49 eyes of 35 patients from 16 articles were finally included for analysis, among which, 17 patients were male, 13 patients were female, and 5 patients were unknown gender; 16 involved left eyes, 19 involved right eyes, and 14 involved unidentified eyes. The age of the disease onset was 42.33±2.19 years (28-59) years old. There were 19 cases with a positive family history, and the total positive rate was 54.3% (19/35, 95%CI 36%-72%). There were 31 cases of gene mutation, all of which were TIMP3. In the included literature, there were 2 and 2 cases with no mutation and unreported loci, respectively, with a total positive rate of 93.9% (31/33, 95%CI 85%-100%). Among the 31 cases with gene mutation, 22, 4, 1, and 4 cases were in the UK, Germany, Switzerland, and Chinese, respectively, and the detection rates were all 100% (22/22, 4/4, 1/1, 4/4). The clinical manifestations of SFD were mainly yellow-white deposits in the fundus and choroidal neovascularization (CNV) in the macula, thereby leading to a decrease in central vision, followed by the expansion of the deposits to the periphery, the further development of CNV, and a severe decline in vision caused by peripheral retinal and choroidal atrophy. The treatment methods for SFD include photodymatic therapy, anti-VEGF drugs, glucocorticoids, vitamin A, etc., among which, anti-VEGF drugs were considered the first-line treatment, and the combined treatment was provided with a better prognosis than a single treatment. ConclusionsVariations in the TIMP3 gene cause SFD, the fundus characteristic manifestations of which, are yellowish-white deposits and CNV, which develop from the center to the periphery, thus resulting in progressive decline of visual acuity. Current studies have shown that combined therapy presents a better prognosis than monotherapy.
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.