Objective To investigate the role of bone marrow-derived cells (BMC) plays in choroidal neovascularization (CNV).Methods Green fluorescent protein (GFP) chimeric mice were built by transplanting BMC from GFP transgenic mice to adult wild type C57BL/6J mice. Retinal laser photocoagulation was used to induce CNV in the chimeric mice (treated group) and adult wild type mice (control group). Four weeks later, choroidal flatmount was prepared to detect GFP positive BMC expression in the CNV lesions, and immunofluorescence stain was used to determine the expression of vascular endothelia growth factor (VEGF) and basic fibroblast cell growth factor (bFGF).Results Twenty-nine days after photocoagulation lots of GFPpositive BMC presented in the CNV area, which accounted approximate 16.22% of the total CNV area. Some BMC in the CNV area expressed VEGF and bFGF. Conclusions BMC may play an important role in CNV by forming new vessles and secreting angiogenic factors.
ObjectiveTo observe the clinical efficiency of intravitreal Conbercept on exudative age-related macular degeneration (eAMD).
MethodsThis is an open and prospective study without control trial. Twenty eyes from 20 patients (19 males and 1 female) with eAMD diagnosed by fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were enrolled in this study. Before the injection, best-corrected visual acuity (BCVA) of early treatment of diabetic retinopathy study (ETDRS), non-contact tonometer, ophthalmoscope, fundus photography, fundus fluorescein angiograph (FFA), indocyanine green angiography (ICGA) and optical coherence tomography (OCT) were examined. The initial average letters of ETDRS acuity were 41.20±22.61, range from 8 to 80. The initial average central retina thickness (CRT) was (345.25±131.96) μm, range from 152 to 770 μm.All affected eyes were treated with intravitreal conbercept 0.05 ml (10 mg/ml). The patients were followed up for 6 to 9 months, with the mean time of (7.35±0.99) months.The BCVA, CRT after treatment were compared with baseline using paired t-test.
ResultsDuring the 1, 3, 6, 12 months after treatment and the latest follow up, the mean BCVA were all improved with statistically significant difference (t=5.85, 7.09, 7.44, 7.25; P < 0.05). At 1 month ater treatment, the mean BCVA was obviously improved in 6 eyes (30%), improved in 8 eyes (40%), stable in 6 eyes (30%). At latest follow up, the mean BCVA was obviously improved in 6 eyes (30%), improved in 9 eyes (45%), stable in 5 eyes (25%). During the 1, 3, 6, 12 months after treatment and the latest follow up, the mean CRT were all decreased with statistically significant difference (t=3.34, 3.78, 3.47, 3.44; P < 0.05). At latest follow up, the leakage in macula lutea disappeared in 6 eyes (30%), decreased in 11 eyes (55%) and increased in 3 eyes (15%). No adverse events such as secondary retinal detachment or endoophthalmitis were found during the follow-up duration.
ConclusionIntravitreal conbercept is a safe and effective approach for eAMD, may improve visual acuity, exudation and macular edema.
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.
Objective To investigate the related factors of effects on distant visual acuity after photodynamic therapy (PDT) for choroidal neovascularization (CNV). Methods One hundred and thirty-five cases (135 eyes ) of CNV treated with PDT were observed. The gender, preoperative distant and near visual acuity, disease course, pathogeny, area of CNV, types of CNV ascertained by fundus fluorescein angiography (FFA), and changes of CNV in FFA were recorded. Multi-factor regression analysis of visual acuity within 1 month and 3 months after PDT was performed with SPSS statistics software. Results The distant visual acuity within 1 month postoperatively was related to the preoperative distant visual acuity, the area of CNV and the changes in the FFA（P=0.000,0.030,0.062）, and 3 months after PDT, it was related to the distant and near visual acuity preoperatively and the changes in the FFA（P=0.000,0.054,0.034）. The condition of distant visual acuity within 1 month postoperatively was related to the FFA type of CNV and the disease course（P=0.018,0.08）. Conclusion The smaller the area of CNV is, the better postoperative distant visual acuity would be. The proportion of improvement of visual acuity is relatively higher in patients with classic CNV. Early treatment for the patients with the indicatio may improve the visual acuity effectively. (Chin J Ocul Fundus Dis，2004，20：292-294)
ObjectiveTo observe the changes in choroidal characteristics of polypoid choroidal vascular disease (PCV) eyes after intravitreal injection of anti-VEGF drugs, and to preliminarily evaluate its predictive effect on the response of PCV anti-VEGF drugs.MethodsA retrospective clinical study. From January 2015 to May 2020, 63 eyes (63 PCV patients) diagnosed in NanJing Medical University Eye Hospital were included in the study. There were 39 eyes (39 males) and 24 eyes (24 females); all were monocular, with the average age of 62.53±6.05 years old. All eyes were treated with intravitreal injection of ranibizumab, and those with poor response after treatment were treated with photodynamic therapy (PDT) combined with anti-VEGF drugs. Among the 63 eyes, 38 eyes did not respond or responded poorly after treatment, and 25 eyes responded well. Based on response results, patients were divided into the poor response group and the good response group. The confocal laser synchronous angiography system (HRA+OCT) enhanced depth scanning technology of Herdelberg (Germany) was used to measure the foveal choroid thickness (SFCT) and the choroidal large vessel thickness (LCVT). The choroidal hyperpermeability (CVH) was judged based on the ICGA inspection results. CVH: In the middle and late stages (10-15 min after indocyanine green injection), the choroid of the posterior pole can be seen with multifocal strong fluorescence with blurred edges. The SFCT and LVCT changes of the two groups of eyes before treatment and 6 months after treatment in the good response group, and 6 months after the treatment of the poor response group combined with PDT were observed. SFCT and LCVT were compared with t test before and after treatment.ResultsBefore treatment, of the 63 eyes, 38 eyes (60.3%) with CVH manifestations, of which 5 eyes (20.0%, 5/25) and 33 eyes (86.8%, 33/ 38). The SFCT and LCVT of the good response group and the poor response group were 244.16±23.74, 152.76±22.70 μm and 367.34±35.21, 271.84±35.42 μm, respectively. The comparison of SFCT and LVCT between the two groups of eyes before treatment showed statistically significant differences (t=7.24, 6.87; P=0.01, 0.01). Six months after treatment, the SFCT and LVCT of the eyes in the good response group were 241.04±32.56 and 150.44±23.45 μm, respectively; compared with those before treatment, the difference was not statistically significant (t=5.35, 8.64; P=0.08, 0.07). Six months after the poor response group combined with PDT treatment, SFCT and LCVT were 311.63±25.36 and 220.11±41.30 μm respectively; compared with those before treatment, the difference was statistically significant (t=6.84, 9.23; P=0.02, 0.01). After treatment, the CVH manifestations of all the eyes did not change significantly, but the eyes of the poor response group were treated with PDT, and the multifocal strong fluorescence was significantly weakened.ConclusionsPCV thick choroid is mostly caused by abnormal thickening of choroidal large vessels. Eyes with thick choroid and CVH have poor response to anti-VEGF drug therapy alone, and combined PDT therapy may be more suitable for this type of patients.
Choroidal neovascularization is the leading causes of central vision loss in wet age-related macular degeneration (wAMD) patients. Smoking not only aggravates the incidence and severity of the choroidal neovascularization of wAMD, but also affects the clinical treatment, making the prognosis worse. Nicotine, as an important harmful substance in tobacco, is an easily addictive and highly toxic alkaloid. Animal experiments and clinical studies have confirmed that nicotine can aggravate wAMD by mediating angiogenesis through nicotinic acetylcholine receptor, bone marrow blasts, inflammation, complement system, etc. Therefore, in order to early take appropriate intervention measures to prevent and delay the development, we should actively explore the exact pathogenesis by which nicotine aggravates the choroidal neovascularization.
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.
Objective To investigate the effects of celecoxib-poly lactide-co-glycolide microparticles (CEL-PLGA-MS) on rat retina after intravitreal injection. Methods A total of 32 male Brown Norway rats were randomly divided into CEL-PLGA-MS group and celecoxib group, 16 rats in each group. The rats in CEL-PLGA-MS group were divided into four dosage group, four rats in each group, which received intravitreal injection of PLGA with celecoxib at the concentration of 40, 80, 160, 320 mu;mol/L, respectively. The rats in celecoxib group were divided into four dosage group, four rats in each group, which received intravitreal injection of celecoxib at the concentration of 40, 80, 160, 320 mu;mol/L, respectively. Phosphate buffer solution (PBS) was injected in two rats as PBS control group. Two rats as normal control group received no treatment. The difference of retinal thickness among groups was measured by optical coherence tomography (OCT). The morphological and histological change of retina was evaluated under light microscope and transmission electron microscope. Results There was no difference of retinal thickness between normal control group and PBS control group (F=0.12,P＞0.05). At the first week after injection, the retinal thickness of CEL-PLGA-MS group and celecoxib group were thicker than that in normal control group and PBS control group (F=9.62, 46.13;P＜0.01). The retinal thickness of celecoxib group was thicker than that in CEL-PLGA-MS group (F=165.15,P＜0.01). The retinal thickness was estimated equal among 40, 80, 320 mu;mol/L dosage groups in CEL-PLGA-MS group (F=4.79,P＜0.01). The retinal thickness of 160, 320 mu;mol/L dosage group were thicker than that in 40, 80 mu;mol/L dosage group in celecoxib group (F=28.10,P＜0.01). At the second week after injection, there was no difference of retinal thickness between CEL-PLGA-MS and celecoxib group (F=3.79,P＞0.05); the retinal thickness of CEL-PLGA-MS and celecoxib group became thinner gradually compare to the first week after injection (F=7.28, 103.99; P＜0.01). At the fourth week after injection, the retinal thickness of celecoxib group was thicker than that in CEL-PLGA-MS group (F=19.11,P＜0.01). The retinal thickness of CEL-PLGA-MS group was approximately the same to normal control group and PBS control group (F=2.02,P＞0.05). The retinal thickness of celecoxib group was thicker than that in normal control group and PBS control group. No considerable abnormality of the retina was seen by light microscope and the retinal thickness corresponded with the values measured by OCT at the first week after injection. The abnormal structures of the retina were seen in 160, 320 mu;mol/L dosage group of celecoxib group and inner changed evidently by the transmission electron microscope. Disordered arrangement of microfilaments, dilated microtubule and some mitochondria vacuolation were observed in 320mu;mol/L dosage group of celecoxib group. Others changed slightly. Conclusions CEL-PLGA-MS has less toxicity on the retina than free-celecoxib after intravitreal injection. The safety of intravitreal injection with CEL-PLGA-MS is better than celecoxib.
Objective To compare the consistency and difference of optical coherence tomography angiography (OCTA) and traditional multimodal fundus imaging in the diagnosis and activity evaluation of choroidal neovascularization (CNV) in exudative age-related macular degeneration (AMD). Methods A total of 112 exudative AMD patients (130 eyes) were included in this retrospective study, 62 were men (71 eyes) and 50 were women (59 eyes). The mean age was (68.250±9.789) years (range 50 – 91 years). All patients were underwent traditional multimodal fundus imaging including fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA) and spectral domain optical coherence tomography (OCT); OCTA was performed at the same time. The CNV type was divided into active and non-active according to the results of traditional multimodal fundus imaging. The vascular pattern was divided into active and non-active according to the results of OCTA. Using traditional multimodal fundus imaging as the standard, the sensitivity and specialty of OCTA was evaluated. Results In 130 eyes, CNV was visualized on traditional multimodal fundus imaging in 109 eyes (83.8%); CNV was visualized on OCTA in 103 eyes (79.2%), which including 7 eyes of false negative and 1 eye of false positive. The sensitivity of OCTA for CNV diagnosis was 93.6%, with specificity of 95.2%. The CNV detection rate between two methods had no significant difference (Youden index=0.89,Kappa value=0.796,P=0.07). In 109 eyes diagnosed with CNV by traditional multimodal fundus imaging, 73 eyes (67.0%) were active CNV and 36 eyes (33.0%) were non-active CNV; the vascular pattern was active in 60 eyes (55.0%) and non-active in 49 eyes (45.0%). The sensitivity of OCTA for the detection of active CNV was 82.2%, with specificity of 100.0%. The active CNV detection rate between two methods had no significant difference (Youden index=0.82,Kappa value=0.753,P=0.00). Conclusion In the diagnosis and activity evaluation of CNV in exudative AMD, there is remarkable consistency between OCTA and traditional multimodal fundus imaging.
Macrophages are major effecter cells of nonspecific immune response, the polarization of which plays a great role in inflammation, repairing and angiogenesis. According to functional phenotypes, macrophages can be polarized to classically activated type (M1), which could promote angiogenesis, and alternatively activated type (M2), which could inhibit angiogenesis. The proportion of M1/M2 could modulate the growth of choroidal neovascularization (CNV). Under the conditions of aging and injury within the retina, macrophages may polarize to M2, which could generate several proangiogenic factors, initiating and promoting the formation of angiogenesis and fibrous scar. Therefore, regulation of macrophage polarization is expected to inhibit angiogenesis and provide new insight for treatment of CNV.
