Wet age-related macular degeneration (wAMD) is caused by choroidal neovascularization (CNV), which occurs when the choroidal new capillaries reach the RPE layer and photoreceptor cell layer through the ruptured Bruch membrane, leading to neovascularization bleeding, leakage, and scarring. In view of the important role of VEGF in the development of CNV, targeted therapy with various intraocular anti-VEGF drugs is the first-line treatment for wAMD. However, the efficacy of anti-VEGF drugs in the treatment of wAMD is affected by a variety of factors, and some patients still have problems such as unresponsiveness, drug resistence, tachyphylaxis, long-term repeated injections, and severe adverse effects. It is the direction of future researches to deeply explore the physiological and pathological process of wAMD, find the cause of CNV formation, and seek better therapies.
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.
Objective To observe the efficacy and safety of intravitreal injection of Ranibizumab(Lucentis) on exudative age-related macular degeneration (AMD). Methods To analyze retrospectively the clinical data of 56 patients with exudative AMD, which was diagnosed by examination of ETDRS charts, color fundus photograph, fluorescein angiography(FFA) or indocyanine green angiography(ICGA) and optical coherence tomography(OCT), were underwent intravitreal injection Lucentis 0.5 mg. Before the treatment, the ETDRS charts letter of 56 eyes was 25.1; choroidal neovascularization(CNA) was leaky which examined by FFA and ICGA; the average thickness of retina was 303.45 mu;m. Ranibizumab injection therapeutic times were 2.8, the average therapeutic times were 3.1. Follow-up time was 6-12 months (mean 8.7 months). Visual acuity (ETDRS charts letter), retinal thickness, leakage of CNV and operative complications before and after the treatment were analyzed. Results At the end of the follow-up period, the mean letter of ETDRS charts was 38.5, increased 13.4 letters (P<0.01), the ETDRS charts improved 15 or more letters in 22 eyes (39.3%), decreased more than 15 letters in 2 eyes (3.6%); the foveal thickness on OCT images were 303.45 mu;m before treatment and 191.35 mu;m a fter treatment, decreased significantly (P<0.00); FFA and/ or ICGA showed CNV complete closure in 12 eyes (21.4%), partial closure in 33 eyes (58.9%), no change in 9 eyes (16.1%) and new CNV in 1 eye (1.8%); Slight complications after operation disappeared during one week. Conclusion Intravitreal injection of Ranibizumab for exudative AMD was well tolerated, with an improvement in VA, FFA or ICGA , and OCT. (Chin J Ocul Fundus Dis,2008,24:160-163)
Objective To observe the inhibitory effects and characteristics of intravitreal injection with bevacizumab on laser induced choroidal neovascularization (CNV).Methods Twelve male brown norway(BN)rats were divided into the bevacizumab group and control group with six rats in each group. One eye of rats were received a series of 8 diode laser esions around optic disc to induce CNV,then the rats in bevacizumab group and control group underwent intravitreal injection with 2 mu;l bevacizumab and ringer's lactate.On days 7,14,and 21,the morphology and leakage of CNV were observed by fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA).On day 21 after photocoagulation,the photocoagulated eyes were enucleated and processed for histopathologic examination, including hematoxylin and eosin (Hamp;E) staining and immunohistochemistry staining for vascular endothelial growth factor(VEGF).Results On day 7 after photocoagulation,ICGA showed that CNV developed in the bevacizumab group and the control group. FFA showed that leakage intensity in the bevacizumab group was significantly lower than that in the control group,but the bevacizumab group gradually increased over time. The mean thickness of CNV significantly decreased in the bevacizumab group.The CNV in the bevacizumab group were negative for VEGF according to the result of immmuohistochemistry staining.Conclusions Early intravitreal injection with 2 mu;l bevacizumab can reduce the thickness of CNV and inhibit the leakage of CNV. However, bevacizumab could neither block the formation of CNV, nor suppress the permeability permanently. Combined other therapies with bevacizumab may be more potential to treat CNV effectively.
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.
Objective To observe the clinical effects and safety of Bevacizumab on recurrent idiopathic choroidal neoascularization(CNV). Methods To analyze retrospectively the clinical data of 21 eyes of 20 patients with recurrent idiopathic CNV who had intravitreal injection of Bevacizumab(0.05 ml 1.25 mg) after signing the letter of consent. In these patients, 12 cases (13 eyes) had been cured by photodynamic therapy (PDT), and 8 cases (8 eyes) had been cured by transpupillary thermotherapy (TTT). The follow-up periods were 2 weeks, 1 month, 3 months and 6 months after injection. The inspection findings of best-corrected visual acuity(BCVA), fundus fluorescein angiography (FFA) and optical coherence tomogr aphy (OCT) before and after the treatment were observed and analyzed. It could inject once more by the same way if there are recurrences in follow-up period. Results At the end of follow-up period, the BCVA improved obviously (gt;1 lines) in 14 eyes (66.7%),kept stable (changed within 1 line)in 5 eyes (23.8%) and decreased (gt;1 lines) in 2 eyes(9.5%). The complete closure of CNV in 17 eyes (81.0%) and partial closure in 4 eyes (19.0%) were observed by FFA images. The thickness of retina in macular region decreased 115 micron. 3 eyes (14.3%) has inject again during follow-up period. The intraocular pressure increased in 4 eyes(19.0%) , the average intraocular pressure was 26.7 mm Hg(1 mm Hg=0.133 kPa). They have been returned to normal through the treatment. There was no serious adverse reaction in process of treatment. Conclusion Intravitreal infection of Bevacizumab can reduce the leakage of recurrent CNV and macular edema after PDT or TTT. About 2/ 3 patients can improve their visual acuity obviously. No severe complication or adverse reaction was observed in this study. (Chin J Ocul Fundus Dis,2008,24:168-171)
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.
Objective To observe the baseline characteristics and visual outcomes after two years follow-up of exudative age-related macular degeneration (AMD) patients treated with ranibizumb. Methods Forty-four eyes of 44 patients with exudative AMD were enrolled into this retrospective study, 19 were men and 25 were women. The mean age was 78 years (range 64 – 92 years). All patients were underwent best corrected visual acuity (BCVA, Early Treatment of Diabetic Retinopathy Study), fundus color photography, fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA) and optical coherence tomography (OCT). The mean BCVA was (50.36±14.43) letters, the mean central foveal thickness (CFT) was (291.95±82.19) μm, and the fluorescence leakage area of choroidal neovascularization (CNV) was (7.61±5.84) mm2. All patients received three initial intravitreous injection of ranibizumb (IVR) and were retreated with monthly IVR when needed. The mean follow up time was 25.6 months (range 24 – 29 months). On 1, 2, 3, 6, 12, 18 and 24 months after treatment, BCVA and OCT were repeated. On 3, 6, 12, 18 and 24 months after treatment, FFA and ICGA were repeated. The change of BCVA, CFT and fluorescence leakage area of CNV were observed. The association of baseline characteristics and two year visual outcomes were analyzed. Results On 1, 2, 3, 6, 12, 18 and 24 months after treatment, the BCVA were improved significantly (t= −1.89, −3.51, −4.61, −4.04, −5.77, −4.69;P<0.05), the CFT were decreased significantly (t=1.51, 2.30, 3.40, 3.28, 3.54, 3.88, 3.73;P<0.05). On 3, 6, 12, 18 and 24 months after treatment, the fluorescence leakage area of CNV were reduced significantly (t=2.12, 2.90, 3.51, 4.12, 4.06;P<0.05). The lower baseline BCVA, the more improved after treatment. The BCVA improvement degree has a negative relationship with baseline BCVA and fluorescence leakage area of CNV (r=0.505, −0.550;P<0.05), but no correlation with baseline CFT (r=0.210,P>0.05). Conclusion Two year visual outcomes of exudative AMD patients treated with ranibizumb is negative correlated with baseline BCVA and fluorescence leakage area of CNV, but not correlated with baseline CFT.
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.
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.