ObjectiveTo observe and analyze the influencing factors for the prognosis of anti-vascular endothelial growth factor (VEGF) drug treatment in patients with macular neovascularization (MNV) under 45 years old. MethodsA retrospective clinical case study. A total of 89 MNV patients with 96 eyes who were diagnosed and treated with anti-VEGF drugs in Department of Ophthalmology of The Second Hospital of Lanzhou University from January 2020 to January 2024 were included in the study. The ages of all patients were ＜45 years old. All patients underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations; 49 eyes underwent OCT angiography (OCTA) examination. The BCVA examination was carried out using the international standard visual acuity chart and was converted into the logarithm of the minimum angle of resolution (logMAR) visual acuity for statistics. The macular foveal thickness (CMT) was measured using an OCT instrument. The size of the MNV lesion was measured using the software of the OCTA self-contained device. The affected eyes were given intravitreal injection of anti-VEGF drugs once, and then the drugs were administered as needed after evaluation. The follow-up time after treatment was ≥6 months. During the follow-up, relevant examinations were performed using the same equipment and methods as before treatment. The last follow-up was taken as the time point for efficacy evaluation. According to the OCT image characteristics of the MNV lesions, the affected eyes were divided into the fibrous scar group and the non-fibrous scar group, with 52 (54.16%, 52/96) and 44 (45.83%, 44/96) eyes respectively. Comparing the CMT and BCVA at the last follow-up with those at the baseline, the affected eyes were divided into the CMT reduction group, the CMT increase group, the BCVA improvement group and the BCVA reduction group, with 66 (68.75%, 66/96), 30 (31.25%, 30/96) eyes and 74 (77.08%, 74/96), 22 (22.92%, 22/96) eyes respectively. The Mann-Whitney U test was used for the comparison of non-normally distributed measurement data between groups. Logistic regression analysis was used to analyze the independent factors affecting the prognosis of MNV patients. ResultsThere were no statistically significant differences in the age (Z=?0.928) and gender composition ratio (χ2= 0.123) between the fibrous scar group and the non-fibrous scar group (P＞0.05); there were statistically significant differences in the number of eyes with a follow-up time of ≥36 months and ＜36 months (χ2= 3.906, P=0.048); there were statistically significant differences in the size of the MNV lesions (Z=?2.385, P=0.017); there were statistically significant differences in the number of eyes with different vascular network morphologies (χ2=12.936, P=0.001). Before treatment and at the last follow-up, the CMT of the affected eyes was 267.50 (237.25, 311.75) μm and 242.00 (217.25, 275.75) μm respectively; logMAR BCVA was 0.20 (0.10, 0.50) and 0.35 (0.16, 0.60) logMAR respectively. There were statistically significant differences in the CMT and logMAR BCVA before treatment and at the last follow-up (Z=?3.311,?1.984; P=0.001, 0.047). There were statistically significant differences in different ages (Z=?2.284), myopic diopter (χ2=7.437), etiology (χ2=6.956), and disease course (Z=?1.687) between the CMT reduction group and the CMT increase group (P＜0.05). There were statistically significant differences in the number of eyes with different subjective feelings between the BCVA improvement group and the BCVA reduction group (χ2=10.133, P＜0.05). The results of logistic regression analysis showed that the etiology was an independent risk factor for CMT thickening. ConclusionsAge, etiology, myopic diopter, disease course, follow-up time, lesion size and the morphology of the neovascular network are the influencing factors for the prognosis of anti-VEGF drug treatment in MNV patients under 45 years old. The etiology is an independent risk factor for CMT increase.
Objective To observe the multimodal image features of inflammatory lesions and choroidal neovascularization (CNV) in multifocal choroiditis (MFC). MethodsA retrospective clinical analysis. A total of 90 eyes of 46 patients with MFC diagnosed in the Department of Ophthalmology of Yunnan University Affiliated Hospital from May 2017 to April 2021 were included in the study. Among them, there were 21 males and 25 females; the average age was 38.30±8.97 years old. Twenty-nine cases of MFC were diagnosed in the past, and they visited the doctor again due to new symptoms; 17 cases without a clear past medical history were the first visits. All eyes underwent color fundus photography, fluorescein fundus angiography (FFA), optical coherence tomography (OCT), and OCT angiography (OCTA). With reference to the literature and the results of multimodal fundus imaging examinations, MFC lesions were divided into active CNV lesions, inactive CNV lesions, active inflammatory lesions, and inactive inflammatory lesions, with 31 (34.4%, 31/90), 12 (13.3%, 12/90), 26 (28.9%, 26/90), 90 (100.0%, 90/90) eyes. Nineteen eyes were treated with anti-vascular endothelial growth factor drugs. To summarize and analyze the manifestations of inflammatory lesions and CNV lesions in different imaging examinations. The Wilcoxon rank test was used to compare the detection rate of CNV lesions between FFA and OCTA. ResultsIn eyes with active inflammatory lesions and active CNV lesions, yellow-white lesions, retinal hemorrhage and exudation were seen on fundus color photography; FFA examination showed fluorescein leakage in the lesions; OCT examination showed retinal pigment epithelium (RPE) layer in the lesions was uplifted, the boundary was unclear, combined with subretinal and intraretinal fluid; OCTA examination showed that there was no blood flow signal in each layer of vascular tissue in active inflammatory lesions, and blood flow signals were seen in active CNV lesions. In the eyes of inactive inflammatory lesions and inactive CNV lesions, the fundus color photography showed that the lesions had clear boundaries without bleeding or exudation; FFA examination, the lesions were fluorescently stained, and there was no fluorescein leakage; OCT examination, inactive CNV lesions manifested as raised lesions with clear boundaries, and inactive inflammation manifested as scars formed by mild RPE hyperplasia or depressions in outer structures formed by atrophy; OCTA examination, inactive inflammatory lesions showed patchy loss of blood flow signal or penetrating blood flow signal below, blood flow signal can be seen in inactive CNV lesions. ConclusionMFC active inflammatory lesions and active CNV lesions are often accompanied by retinal hemorrhage and exudation; FFA shows fluorescein leakage; OCT shows that the boundary of raised lesions is unclear; OCTA can identify the nature of CNV or inflammatory lesions.
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 investigate whether desferrioxamine (DFO) can enhance the homing of bone marrow mesenchymal stem cells (BMSCs) and improve neovascularization in random flaps of rats.MethodsBMSCs and fibroblasts (FB) of luciferase transgenic Lewis rats were isolated and cultured. Forty 4-week-old Lewis male rats were used to form a 10 cm×3 cm rectangular flap on their back. The experimental animals were randomly divided into 4 groups with 10 rats in each group: in group A, 200 μL PBS were injected through retrobulbar venous plexus; in group B, 200 μL FB with a concentration of 1×106 cells/mL were injected; in group C, 200 μL BMSCs with a concentration of 1×106 cells/mL were injected; in group D, cells transplantation was the same as that in group C, after cells transplantation, DFO [100 mg/(kg·d)] were injected intraperitoneally for 7 days. On the 7th day after operation, the survival rate of flaps in each group was observed and calculated; the blood perfusion was observed by laser speckle imaging. Bioluminescence imaging was used to detect the distribution of transplanted cells in rats at 30 minutes and 1, 4, 7, and 14 days after operation. Immunofluorescence staining was performed at 7 days after operation to observe CD31 staining and count capillary density under 200-fold visual field and to detect the expressions of stromal cell derived factor 1 (SDF-1), epidermal growth factor (EGF), fibroblast growth factor (FGF), and Ki67. Transplanted BMSCs were labeled with luciferase antibody and observed by immunofluorescence staining whether they participated in the repair of injured tissues.ResultsThe necrosis boundary of ischemic flaps in each group was clear at 7 days after operation. The survival rate of flaps in groups C and D was significantly higher than that in groups A and B, and in group D than in group C (P<0.05). Laser speckle imaging showed that the blood perfusion units of flaps in groups C and D was significantly higher than that in groups A and B, and in group D than in group C (P<0.05). Bioluminescence imaging showed that BMSCs gradually migrated to the ischemia and hypoxia area and eventually distributed to the ischemic tissues. The photon signal of group D was significantly stronger than that of other groups at 14 days after operation (P<0.05). CD31 immunofluorescence staining showed that capillary density in groups C and D was significantly higher than that in groups A and B, and in group D than in group C (P<0.05). The expressions of SDF-1, EGF, FGF, and Ki67 in groups C and D were significantly stronger than those in groups A and B, and in group D than in group C. Luciferase-labeled BMSCs were expressed in the elastic layer of arteries, capillaries, and hair follicles at 7 days after transplantation.ConclusionDFO can enhance the migration and homing of BMSCs to the hypoxic area of random flap, accelerate the differentiation of BMSCs in ischemic tissue, and improve the neovascularization of ischemic tissue.
Objective To analyze the characteristics of myopic choroidal neovascularization (mCNV) and the outcome of intravitreal anti-vascular endothelial growth factor (VEGF) treatment by using optical coherence tomography angiography (OCTA). Methods A prospective study was carried out, which included 34 eyes of 31 patients with mCNV in West China Hospital of Sichuan University between May and December 2017. OCTA scans were conducted to all patients before treatment, 1 day, 1 week, 1 month and 3–6 months after treatment. The analysis was performed to evaluate the morphological characteristics, lesion area, parafoveal superficial vessel density and perfusion area of choroidal neovascularization before and after treatment. Results Among mCNV patients, small round crumby lesions, small branches, and capillaries responded well to anti-VEGF treatment. Compared with the mean lesion area in mCNV patients before treatment [(0.082±0.013) mm2], there was instant reduction 1 day after treatment [(0.064±0.013) mm2] and obviously decreased after 1 week [(0.046±0.011) mm2]. The parafoveal superficial vessel density and perfusion area before treatment were (15.2±0.5)% and (32.6±1.5)%, respectively, and obvious decrease was observed both in parafoveal superficial vessel density [(12.1±0.9)%] and perfusion area [(27.4±2.0)%] 1 day after treatment in mCNV patients, which began to recover 1 month after treatment. Conclusions OCTA is a non-invasive diagnostic examination, which can clearly identify tiny structures of mCNV, quantify the lesion area and display specific vasculature in mCNV patients. Furthermore, retinal microcirculation can be detected by using OCTA, which provides an effective approach of monitoring the progression and treatment effect of mCNV.
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 OCT angiography (OCTA) features of adult-onset foveomacular vitelliform dystrophy (AFVD).MethodsRetrospective clinical observational study. Twelve patients (22 eyes) diagnosed as AFVD by multi-modal imaging in Ophthalmology Department of Yunnan Second People’s Hospital from March 2018 to May 2019 were included in this study. There were 8 males (16 eyes) and 4 females (6 eyes). The patients aged from 33 to 62 years, with the mean age of 48.7±8.9 years. Ten patients were binocular, 2 patients were monocular. The visual acuity was 0.08-0.6. In 22 eyes, the vitelloid-like substance was relatively complete in 8 eyes, the vitelloid-like substance had different degrees of rupture in 14 eyes, secondary choroidal neovascularization (CNV) was observed in 10 eyes. The Heidelberg OCTA instrument was used for OCTA examination. The central wavelength was 840 nm, the acquisition speed was 85,000 times/s. A 3 mm × 3 mm scan was obtained. In the scanning process, eye-tracking technology was adopted to select images with better image quality and position for marking and saving. The image characteristics of vitelloid-like substance, fundus vascular changes and secondary CNV in OCTA were analyzed.ResultsIn 8 eyes with a relatively complete vitelloid-like substance, B-scan images showed dense vitelloid-like substance under the retinal neurocortical layer, which was located between the RPE layer and the ellipsoid zone and had a uniform density. Blood flow signals at the vitelloid-like substance can be seen in the en-face image, which was the artifact of the vitelloid-like substance reflecting the blood vessels above. In the 14 eyes with different degrees of vitellin-like material rupture, the signal of vitellin-like substance between the ellipsoid zone and the RPE layer in the B-scan image was not uniform, and some weak reflected signal lacunae could be seen. In the image of en-face, the relatively intact areas of vitelloid-like substance still showed the artifact of the blood vessels above the reflection, while there was no blood flow signal at the rupture of vitelloid-like substance. In 22 eyes, the morphology of retinal small blood vessels in the superficial and deep capillary arch ring region of retina was abnormal in 10 eyes. Some small blood vessels could be seen to have branch and shape changes, and the anastomosis failed to show a complete arch ring structure.No significant structural changes in retinal capillaries were observed in 12 eyes. Among the 10 eyes with secondary CNV, 8 eyes showed the non-active CNV which was as thick as "wild branches", and 2 eyes showed the active CNV which was composed of dense and small vascular branches.ConclusionAFVD in OCTA can be manifested as abnormal retinal vascular morphology caused by the vitelliform material pushing, vascular artifacts reflected by the vitelliform material itself, and the presence of CNV under the vitelliform material.
ObjectiveTo investigate the inhibitory effect of lentivirus-mediated polypyrimidine bundle binding protein-associated splicing factor (PSF) on retinal neovascularization (RNV) in mice model of oxygen-induced retinopathy (OIR).MethodsOne hundred and twelve 5-day-old C57BL/6J mice were randomly divided into normal control group, simple OIR model group, OIR model + lentivirus empty vector treatment group (Vec group) and OIR model + PSF lentivirus treatment group (PSF group), with 16, 32, 32 and 32 mice, respectively. When the mice were 7 days old, the mice in the normal control group were fed in a routine environment, and the mice in the OIR model group, Vec group and PSF group were established OIR model. The mice in the Vec group and PSF group were given an intravitreal injection of 1 μl of lentiviral vector and PSF lentivirus (titer 1×1011 TU/ml) at the age of 12 days. No injection was performed in the normal control group and simple OIR group. RNV was evaluated by counting the number of pre-retinal neovascular cells and analysis of non-perfusion area by immunofluorescent staining of the mouse retina. Real-time quantitative PCR was applied to detect the mRNA expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1). Western blot analysis was applied to detect the protein expression of Nrf2, HO-1 and PSF. Results Of the normal control group, simple OIR model group, Vec group and PSF group, the number of pre-retinal neovascular cell nuclei were 0.00, 14.36±5.50, 15.67±4.96, 8.13±2.09, the non-perfusion area were 0.00%, (35.71±2.81)%, (36.57±4.53)%, (15.33±4.75)%, respectively. The differences of the number of pre-retinal neovascular cell nuclei and non-perfusion area among 4 groups were significant (F=24.87, 165.70; P＜0.05). Compared with the normal control group, there were more pre-retinal neovascular cell nucleis and larger non-perfusion area in the simple OIR model group and Vec group (P＜0.05). Compared with the simple OIR model group and Vec group, there were lower pre-retinal neovascular cell nucleis and smaller non-perfusion area in the PSF group (P＜0.05). Real-time quantitative PCR and Western blot showed that the mRNA expression of Nrf2, HO-1 (F=53.66, 83.54) and protein expression of Nrf2, HO-1 and PSF (F=58.38, 52.69, 24.79) among 4 groups were significant (P＜0.05). The mRNA expression of Nrf2, HO-1 and protein expression of Nrf2, HO-1 and PSF in the simple OIR model group and Vec group decreased significantly than those in the normal control group (P＜0.05). The mRNA expression of Nrf2, HO-1 and protein expression of Nrf2, HO-1 and PSF in the PSF group were increased significantly than those in the simple OIR model group and Vec group (P＜0.05). model group and Vec group (P＜0.05).ConclusionIntravitreal injection of lentivirus-mediated PSF inhibits RNV in mice model of OIR possibly through up-regulating the expression of Nrf2 and HO-1.
Objective To observe the performance of hyperspectral non-mydriatic fundus camera prototype and its application on ocular fundus diseases. Methods The narrow band filters was inserted into the optical path of the Canon non-mydriatic retinal camera (CR-DGi). The image was converted to digital data by charge-coupled device (CCD), and then analyzed by hyperspectral data software. Twelve volunteers were examined by hyperspectral nonmydriatic fundus camera prototype to confirm the characteristic wavelength spectrums of ocular fundus diseases and the repeatability of prototype. Fifty-nine patients with ocular fundus diseases who underwent fluorescein angiography were also examined by hyperspectral non-mydriatic fundus camera prototype, to compared the images of prototype and fluorescein angiography. Results Each of the highest power of the light at the focus point and the power per unit were safe. 536, 547, 579 nm were selected as the specific retinal imaging spectrums and 608 nm as the specific choroidal imaging spectrum. The intra-observer and inter-observer reproducibility was equal or greater than 0.85. The correlation between hyperspectral non-mydriatic fundus camera prototype and fluorescein angiography in choroidal neovascularization patients were 0.782 and 0.833. Conclusions The hyperspectral nonmydriatic fundus camera prototype is safe and reliable. It shows pathological retinal and choroidal structures with specific spectrums. There are good prospects for the application in clinical diagnosis, especially for macular diseases.
Objective To observe the change of serum associated factors concentrations in the patients with idiopathic choroidal neovascularization (CNV).Methods The clinical data of 21 patients (21 eyes) with idiopathic CNV (CNV group) and 20 normal individuals (control group) were retrospective analyzed. Serous concentrations of vascular endothelial growth factor (VEGF), tumor necrosis factor alpha;(TNFalpha;), interleukin 1-beta; (IL1-beta;), IgG, IgA, IgM, IgE, CH50, C3, C4 and Creactive protein (CRP) were assayed by enzymelinked immunosorbent assay (ELISA) and immunonephelometry. Results The level of VEGF in CNV group was significantly higher than that in control group(t=2.340，P=0.025). The level of IgE in CNV group was significantly lower than that in control group(Z=-2.765，P=0.006). The other factors were not significantly different between the two groups（Pgt;0.05）.Conclusion VEGF and IgE may play an important role in the formation of idiopathic CNV.