Objective To observe and evaluate the safety and efficacy of anti-vascular endothelial growth factor (VEGF) in the treatment of eyes with macular edema (ME) secondary to branch retinal vein occlusion (BRVO) in Lhasa, Tibet. MethodsA retrospective case series. From September 2018 to January 2022, a total of 41 patients (41 eyes) with BRVO-ME, who were diagnosed in Department of Ophthalmology of Tibet Autonomous Region People’s Hospital, were included in this study. There were 21 eyes in 21 males and 20 eyes in 20 females. The median age was 53 (31,75) years. There were 24 patients with hypertension (58.8%, 24/41). Best corrected visual acuity (BCVA), ocular pressure, fundus color photography and optical coherence tomography (OCT) were performed in all eyes. The BCVA was performed using the international standard logarithmic visual acuity chart, which was converted into logarithm of the minimum angle of resolution (logMAR) BCVA for record. The foveal macular thickness (CMT) was measured by OCT. All eyes were treated with intravitreous injection of anti-VEGF drugs, once a month, among which 23 eyes (56.1%, 23/41) received intravitreous injection of ranibizumab (IVR), and 18 eyes (43.9%, 18/41) received intravitreous injection of conbercept (IVC), and were grouped accordingly. There was no significant difference in age (Z=－0.447), gender composition (Z=－0.485), logMAR BCVA (t=－1.591), intraocular pressure (t=－0.167) and CMT (t=－1.290) between two groups (P＞0.05). During the follow-up, the same devices and methods were used at baseline to perform relevant examinations, and the changes of BCVA, intraocular pressure, CMT and new cardiovascular and cerebrovascular events were compared between baseline and the last follow-up. logMAR BCVA, intraocular pressure and CMT were compared between baseline and last follow-up using Student t test. The comparison of injection times and follow-up time between IVR group and IVC group was conducted by Mann-Whitney U test. ResultsAt baseline, logMAR BCVA, intraocular pressure, and CMT were 0.852±0.431, (12.5±2.5) mm Hg (1 mm Hg= 0.133 kPa), and (578.1±191.1) μm, respectively. At the last follow-up, the number of anti-VEGF drug treatments was (2.7±1.2) times; logMAR BCVA and CMT were 0.488±0.366 and (207.4±108.7) μm, respectively, with CMT > 250 μm in 14 eyes (34.1%, 14/41). Compared with baseline, BCVA (t=4.129) and CMT (t=－0.713) were significantly improved, with statistical significance (P＜0.001). The injection times of IVR group and IVC group were (2.6±0.9) and (3.0±1.5) times, respectively. There were no significant differences in the number of injection times (t=－1.275), logMAR BCVA (t=－0.492), intraocular pressure (t=0.351) and CMT (t=－1.783) between the two groups (P＞0.05). No new hypertension, cardiovascular and cerebrovascular events occurred in all patients during follow-up. At the last follow-up, there were no eye complications related to treatment modalities and drugs. ConclusionShort-term anti-VEGF treatment can improve the visual acuity of BRVO secondary ME patients and alleviate ME in Lhasa, Tibet. The safety and efficacy of ranibizumab and conbercept were similar.
Anti-vascular endothelial growth factor (VEGF) drugs have been widely used in clinic by inhibiting angiogenesis to treat ocular diseases such as malignant tumors and diabetic retinopathy. However, recent studies have shown that intravitreal injection of anti-VEGF drugs may have significant systemic absorption, leading to a series of renal damages such as worsening hypertension, proteinuria, new glomerular disease, and thrombotic microangiopathy. This article reviews the renal toxicity of intravitreal injection of anti-VEGF drugs in the treatment of diabetic retinopathy and other ocular diseases, aiming to provide recommendations for clinicians.
Objective To observe the efficacy and safety of subretinal injection of Aflibercept for the treatment of refractory or recurrent polypoidal choroidal vasculopathy (PCV). MethodsA prospective clinical research. From January to June 2022, 18 patients of 18 eyes with PCV diagnosed in The Affiliated Eye Hospital of Nanchang University were included in the study. All patients underwent best corrected visual acuity (BCVA), indocyanine green angiography and optical coherence tomography (OCT). The BCVA examination was performed using the international standard visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The large choroidal vessel thickness (LVCT), central retinal thickness (CRT), sub-foveal choroidal thickness (SFCT) and retinal pigment epithelium detachment (PED) height were measured by enhanced depth imaging technique of OCT. The choroidal vascular index (CVI) was calculated. There were 18 patients of 18 eyes, 11 males of 11 eyes and 7 females of 7 eyes. The age was (64.22±3.86) years old. The disease duration was (5.22±1.80) years. The patient had received intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs for (7.72±1.36) times. The logMAR BCVA of the affected eyes was 1.28±0.25. The SFCT, CRT, LVCT, PED height were (436.56±9.80), (432.44±44.29), (283.78±27.10), (342.44±50.18) μm, respectively, and CVI was 0.65±0.01. All eyes were treated with a single subretinal injection of 40 mg/ml Aflibercept 0.05 ml (including Aflibercept 2.0 mg). According to the results of OCT and BCVA after treatment, the lesions were divided into active type and static type. The active lesions were treated with intravitreal injection of Aflibercept at the same dose as before. Quiescent lesions were followed up. Examinations were performed 1-3, 6, 9 and 12 months after treatment using the same equipment and methods before treatment. The BCVA, LVCT, CRT, SFCT, PED height, CVI, interretinal or subretinal fluid, lesion regression rate, injection times, and complications during and after treatment were observed. The BCVA, SFCT, CRT, LVCT, PED height and CVI before and after treatment were compared by repeated measures analysis of variance. ResultsEighteen eyes received subretinal and/or intravitreal injection of Aflibercept (1.61±0.85) times (1-4 times). At the last follow-up, the polypoid lesions regressed in 4 eyes and PED disappeared in 1 eye. Compared with before treatment, BCVA (F=50.298) gradually increased, CRT (F=25.220), PED height (F=144.16), SFCT (F=69.77), LVCT (F=136.69), CVI (F=72.70) gradually decreased after treatment. The differences were statistically significant (P＜0.001). Macular hole occurred in 1 eye after treatment, and the hole closed spontaneously 3 months after treatment. No serious complications such as retinal tear, retinal detachment, endophthalmitis and vitreous hemorrhage occurred during and after treatment. ConclusionSubretinal injection of Aflibercept is safe and effective in the treatment of refractory PCV.
ObjectiveTo explore the effect of vascular endothelial growth factor 165 (VEGF165)-loaded porous poly (ε-caprolactone) (PCL) scaffolds on the osteogenic differentiation of adipose-derived stem cells (ADSCs).MethodsThe VEGF165-loaded porous PCL scaffolds (written, Sf-g/VEGF) were fabricated through a combination of solvent casting/salt leaching and a thermal-induced phase separation technique and then observed under scanning electron microscope (SEM). The release kinetics was determined by ELISA kit. The ADSCs were isolated from inguinal fat pads of 15 Sprague Dawley rats and cultured. The passage 3-4 ADSCs were seeded into the scaffolds, and then cultured in vitro for 7 days. The passage 3-4 ADSCs were seeded into the porous PCL scaffolds (written, Sf-g) as control. The alizarin red S (ARS) staining, ARS activity assay, and real-time quantitative PCR (RT-PCR) were performed to measure the osteogenic differentiation of ADSCs in vitro. Six Sprague Dawley rats were recruited to prepare the bilateral calvarial bone defects models (n=12). The 12 calvarial bone defects were randomly divided into 3 group (n=4). The defects of negative control group were not treated; the defects of Sf-g group and Sf-g/VEGF group were repaired with ADSCs-Sf-g scaffold complex and ADSCs-Sf-g scaffold complex, respectively. At 8 weeks after transplantation, the Micro-CT and HE staining were conducted to evaluate the osteogenic effects in vivo.ResultsThe morphology of the Sf-g/VEGF scaffolds were porous and well-connected, and the cumulative release rate was approximately 80% in 120 hours. The ARS staining showed that the ARS activity of Sf-g/VEGF group were stronger than that of Sf-g group (t=10.761, P=0.000). The mRNA expressions of osteogenic specific markers [special AT-rich sequence protein 2 (Satb2), alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN)] were significantly higher in Sf-g/VEGF group than in Sf-g group (P<0.05). The results of Micro-CT and HE staining also confirmed the promotion effect of Sf-g/VEGF scaffolds. All defects of 2 groups were partially repaired by new bone tissue, especially in Sf-g/VEGF group. The volume and area of new bone tissue were significantly higher in Sf-g/VEGF group than in Sf-g group (P<0.05).ConclusionThe VEGF165-loaded scaffolds can significantly improve the osteogenic differentiation of ADSCs both in vitro and in vivo.
In the American Heart Association’s Scientific Sessions 2021, the results of six clinical trials related to cardiovascular surgery were revealed. The PALACS trial demonstrated that posterior left pericardiotomy during open heart surgery was associated with a significant reduction in postoperative atrial fibrillation; the EPICCURE study found that injection of mRNA encoding vascular endothelial growth factor (VEGF-A mRNA) directly into the myocardium of patients undergoing elective coronary artery bypass grafting (CABG) improved patients’ heart function; the VEST trial once again proved the safety and potential value of external stent for vein graft. This article will interpret the above-mentioned three studies.
ObjectiveTo investigate the significance of the expression of vascular endothelial growth factor (VEGF) in portal vein thrombosis after operation in patients with portal hypertension.MethodsThe serum of 146 patients with portal hypertension treated in Dongfeng Hospital Affiliated to Hubei Medicial College from January 2014 to December 2018 and the surgically removed splenic vein and spleen specimens were collected. The serum VEGF level was determined by enzyme-linked immunosorbent assay, and the expressions of VEGF in splenic vein and spleen tissues were detected by immunohistochemistry. According to whether portal vein thrombosis was formed after operation, the patients were divided into thrombosis group and non-thrombosis group, and the differences between the groups were compared.ResultsThe serum VEGF level in the thrombosis group was significantly higher than that in the non-thrombosis group (P<0.05). In splenic vein wall and spleen tissues, VEGF staining indexes in the thrombosis group were significantly higher than those in the non-thrombosis group (P<0.05).ConclusionsPostoperative portal vein thrombosis in patients with portal hypertension may be related to the serum VEGF level. The high expressions of VEGF in splenic vein wall and spleen suggest that VEGF may participate in the formation process of portal vein thrombosis.
Objective To compare the outcomes of ranibizumab and conbercept adjunct for pars plana vitrectomy (PPV) in the treatment of proliferative diabetic retinopathy (PDR). MethodsA prospective randomized case-control study. From June 2022 to December 2023, 90 cases (90 eyes) of PDR patients diagnosed through ophthalmic examination at Department of Ophthalmology of Gansu Provincial Hospital were included in the study. All patients underwent the best corrected visual acuity (BCVA), intraocular pressure, B-mode ultrasound, and optical coherence tomography (OCT) examinations. The central macular thickness (CMT) was measured using an OCT instrument. The patients were randomly divided into a intravitreal injection of ranibizumab group (monoclonal-antibody group) and a intravitreal injection of conbercept group (fusion-protein group) using a random number table method, with 45 cases (45 eyes) in each group. Two groups of patients were intravitreal injected with 10 mg/ml ranibizumab or conbercept 0.05 ml, respectively. A standard 23G PPV was performed through the flat part of the ciliary body 3-7 days after intravitreal injection. Relevant examinations were performed using the same equipments and methods as before surgery at postoperative 1 week, 1, 3, 6, and 12 months. The PPV time, intraoperative use of intraocular electrocoagulation, incidence of iatrogenic retinal breaks, and sterile air or silicone oil tamponade rate in the vitreous cavity, the postoperative changes of BCVA and CMT, and incidence of complications were compared between two groups. Independent sample t test was used for inter group comparison. ResultsThe intraoperative utilization rate of intraocular electrocoagulation in the monoclonal-antibody group was higher than that in the fusion-protein group, and the difference was statistically significant (χ2=3.876, P＜0.05). There were no statistically significant differences in the PPV time (t=0.152), intraoperative bleeding rate (χ2=0.800), incidence of iatrogenic retinal breaks (χ2=1.975), and sterile air and silicone oil tamponade rate in the vitreous cavity (χ2=1.607, 1.553) between the two groups (P＞0.05). There were no statistically significant differences in early and late postoperative vitreous hemorrhage (χ2=1.235, 2.355), and re-PPV (χ2=2.355) between two groups (P＞0.05). The BCVA of the fusion-protein group was significantly better than that of the monoclonal-antibody group at postoperative 3 months, and the difference was statistically significant (t=2.428, P＜0.05). The CMT of the fusion-protein group was lower than that in the monoclonal-antibody group at postoperative 1 week, and the difference was statistically significant (t=2.739, P＜0.05). None of the patients experienced endophthalmitis, retinal artery occlusion, or severe cardiovascular events after surgery. ConclusionCompared with intravitreal injection of ranibizumab before PPV, intravitreal injection of conbercept before PPV in PDR patients can shorten the surgical time, reduce intraoperative bleeding rate, lower the rate of electrocoagulation and intraocular tamponade, and incidence of iatrogenic retinal breaks, and improve the visual acuity.
Vascular endothelial growth factor (VEGF) is a multifunctional factor that promotes blood vessel formation and increases vascular permeability. Its abnormal elevation plays a key role in common retinal diseases such as wet age-related macular degeneration and diabetic macular edema. Anti-VEGF therapy can inhibit angiogenesis, reduce vascular leakage and edema, thereby delaying disease progression and stabilizing or improving vision. Currently, the clinical application of anti-VEGF drugs has achieved satisfactory therapeutic effects, but there are also issues such as high injection frequency, heavy economy burden, potential systemic side effects, and non-responsiveness. To address these issues, current research and development mainly aim on biosimilars, multi-target drugs, drug delivery systems, oral anti-VEGF drugs, and gene therapy. Some drugs have shown great potential and are expected to turn over a new leaf for anti-VEGF treatment in ophthalmology.
ObjectiveTo analyze the status of applying programmed death-1 (PD-1) / programmed death-ligand 1 (PD-L1) inhibitors combined with vascular endothelial growth factor (VEGF) / vascular endothelial growth factor receptor (VEGFR) inhibitors in advanced refractory colorectal cancer. MethodThe relevant literature on domestic and foreign research in recent years was summarized. ResultsThe discovery of immune checkpoint PD-1/PD-L1 and the clinical application of related drugs had changed the treatment pattern of advanced solid tumors, but PD-1/PD-L1 inhibitors had a poor efficacy in the mismatch repair prodicient tumors, and most advanced colorectal cancer belonged to this type. The combination of PD-1/PD-L1 inhibitors and VEGF/VEGFR inhibitors could enhance the therapeutic effect in the advanced refractory colorectal cancer, and their interaction mechanisms and clinical efficacy were continuously being proven. ConclusionsThe combination of PD-1/PD-L1 inhibitors and VEGF/VEGFR inhibitors is a promising treatment strategy for advanced refractory colorectal cancer. More studies need to be further clarified its efficacy.
Diabetic retinopathy (DR) is the leading cause of visual impairment worldwide. Severe non-proliferative diabetic retinopathy, diabetic macular edema, and proliferative DR (PDR) are defined as vision-threatening DR (VTDR). In the context of managing systemic disease, the primary treatments for VTDR include panretinal photocoagulation (PRP), intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs or dexamethasone sustained release agents, and microincision vitreous surgery. Although these therapies are already widely used in clinical practice, there is still much debate about the optimal timing and method of their application, especially in the pursuit of optimal efficacy, cost-effectiveness, patient compliance, and the reduction of frequent ongoing treatments. There is no consensus on the best treatment for PDR. Determining the specific criteria for each therapy indication is one of the key considerations. In addition, consideration should be given to the priority between PRP and intravitreal injection, as well as to compare the relative effectiveness of anti-VEGF agents with PRP. Early surgical intervention is not always a necessary option for PDR patients with vitreous hemorrhage and fibrovascular membranes. Combining different therapies to optimize treatment strategies is also an important topic. These issues address several points of contention in best practice guidelines that need to be addressed through more in-depth research to provide better guidance for clinical practice and ultimately improve patient outcomes.