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.
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.
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.
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.
ObjectiveTo explore the conversion treatment value of Faricimab in patients with neovascular age-related macular degeneration (nAMD) who had sub-optimal response to anti-vascular endothelial growth factor (VEGF) drug therapy, and to preliminarily evaluate its clinical effect. MethodsA retrospective clinical study. From March 2024 to January 2025, 25 patients (32 eyes) diagnosed with nAMD at Department of Ophthalmology of General Hospital of Central Theater Command were included in the study. All affected eyes were converted to receive Faricimab treatment due to sub-optimal response to previous anti-VEGF drug therapy. The treatment plan is to provide treatment as needed after the first injection based on the follow-up results. The best corrected visual acuity (BCVA) and swept-source optical coherence tomography angiography (SS-OCTA) were evaluated. BCVA examination was conducted using the Snellen visual acuity chart and converted to the logarithm of the minimum angle of resolutionn (logMAR) visual acuity for statistical analysis. The SS-OCTA system automatically calculates indicators such as central retinal thickness (CRT), choroidal neovascularization surface area (CSA), and choroidal neovascularization flow area (CFA). The main observations were made on the changes of BCVA, CSA, CFA, CRT and adverse reactions at 1, 3 and 6 months after treatment. A mixed linear model was adopted to compare the differences between each index and the baseline. ResultsAmong the 25 patients, 20 were male (80.0%, 20/25) and 5 were female (20.0%, 5/25). Age was (66.6±11.2) years old. The disease course was (41.2±36.4) months. Previously received anti-VEGF drug treatment (20.5±21.6) times, involving 2.2 types of drugs. Among the 32 eyes, 16 (50.0%), 11 (34.4%), and 7 (21.9%) eyes had subretinal fluid, intraretinal fluid, and both coexisting, respectively. At baseline, the logMAR BCVA of the affected eye was 0.67±0.41, the CSA and CFA were (7.46±6.27) and (3.26±2.59) mm2, respectively, and the CRT was (380.75±147.56) μm. At 1, 3, and 6 months after switching to Faricimab treatment, logMAR BCVA improved to 0.57±0.42, 0.55±0.41, and 0.50±0.35, respectively. The corresponding CSA were (6.36±6.10), (6.44±6.12), and (6.44±5.96) mm2. The corresponding CFA values were (2.79±2.50), (2.35±2.25), and (2.59±2.35) mm2. The corresponding CRT were (330.64±147.56), (329.44±130.73), (340.05±144.56) μm. Compared with the baseline, BCVA significantly improved at each time point after treatment, and CSA and CFA significantly decreased. The differences were statistically significant (P＜0.05). At 1 and 3 months after treatment, CRT was significantly lower than the baseline, and the difference was statistically significant (P=0.005, 0.025). During the follow-up period, the intraocular pressure of all affected eyes remained normal, and no serious adverse events such as intraocular infection occurred. ConclusionFor nAMD patients with poor response to anti-VEGF drug treatment, switching to Faricimab treatment can effectively improve the BCVA and anatomical structure (including CSA, CFA and CRT) of the affected eyes, and has good safety.
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.
ObjectiveTo compare and analyze the application of anti-vascular endothelial growth factor (VEGF) drugs for intravitreal injection in the real world before and after the establishment of one-stop intravitreal injection center, as well as the advantages and disadvantages of different management modes. MethodsA retrospective clinical study. A total of 4 015 patients (4 659 eyes) who received anti-VEGF drugs for ocular fundus diseases at the Tianjin Medical University Eye Hospital from July, 2018 to June, 2022 were included in the study. There were 2 146 males and 1 869 females. The ocular fundus diseases in this study were as follows: 1 090 eyes of 968 patients with wet age-related macular degeneration (wAMD); 855 eyes of 654 patients with diabetic macular edema (DME); 1 158 eyes of 980 patients with diabetic retinopathy (DR); 930 eyes of 916 patients with macular edema secondary to retinal vein occlusion (RVO-ME). A total of 294 eyes of 275 patients with choroidal neovascularization secondary to pathological myopia (PM-CNV); 332 eyes of 222 patients with other fundus diseases. A total of 13 796 anti-VEGF needles were injected. A total of 1 252 patients (1 403 eyes) from July 2018 to June 2020 were regarded as the control group. From July 2020 to June 2022, 2 763 patients (3 256 eyes) who received anti-VEGF treatment in the intravitreal injection center were regarded as the observation group. The total number of intravitreal injection needles, the distribution of anti-VEGF therapy in each disease according to disease classification, the proportion of patients who chose the 3+ on-demand treatment (PRN) regimen and the distribution of clinical application of different anti-VEGF drugs were compared between the control group and the observation group. The waiting time and medical experience of patients were investigated by questionnaire. χ2 test was used to compare the count data between the two groups, and t test was used to compare the measurement data. ResultsAmong the 13 796 anti-VEGF injections in 4 659 eyes, the total number of anti-VEGF drugs used in the control and observation groups were 4 762 and 9 034, respectively, with an average of (3.39±3.78) and (2.78±2.27) injections per eye (t=6.900, P＜0.001), respectively. In the control and observation groups, a total of 1 728 and 2 705 injections of anti-VEGF drugs were used for wAMD with an average of (5.14±4.56) and (3.59±2.45) injections per eye, respectively; a total of 982 and 2 038 injections of anti-VEGF drugs were used for DME with an average of (4.36±4.91) and (3.24±2.77) needles per eye, respectively. Additionally, a total of 942 and 2 179 injections of anti-VEGF drugs were injected for RVO-ME with an average of (3.98±3.71) and (3.14±2.15) injections per eye, respectively; a total of 291 and 615 injections of anti-VEGF drugs were injected for PM-CNV with an average of (3.31±2.63) and (2.99±1.69) injections per eye, respectively. A total of 683 and 1 029 injections of anti-VEGF drugs were injected for DR with an average of (1.60±1.26) and (1.41±1.05) injections per eye, respectively. The clinical application and implementation of "3+PRN" treatment were as follows: 223 (66.4%, 223/336) and 431 eyes (57.2%, 431/754) in the wAMD (χ2=8.210, P=0.004), 75 (33.3%, 75/225) and 236 (37.5%, 236/630) eyes in the DME (χ2=1.220, P＞0.05), and 97 (40.9%, 97/237) and 355 eyes (51.2%, 355/693) in the RVO-ME (χ2=7.498, P=0.006), 39 (44.3%, 39/88) and 111 eyes (53.9%, 111/206) in the PM-CNV ( χ2=2.258, P＞0.05), respectively. In addition, the results of the questionnaire survey showed that there were significant differences between the control and observation groups regarding the time of appointment waiting for surgery (t=1.340), time from admission to entering the operating room on the day of injection (t=2.780), time from completing preoperative treatment preparation to waiting for entering the operating room (t=8.390), and time from admission to discharge (t=6.060) (P＜0.05). ConclusionsThe establishment of a one-stop intravitreal injection mode greatly improved work efficiency and increased the number of injections. At the same time, the compliance, waiting time, and overall medical experience of patients significantly improved under centralized management.
Neovascularization is a characteristic manifestation of a variety of retinal diseases. Vascular endothelial growth factor (VEGF) mainly regulates the proliferation and migration of endothelial cells. VEGF receptor 2 (VEGFR2) is the main receptor to mediate this effect. The activation of downstream signals requires the binding of VEGF and VEGFR2, followed by receptor dimerization and autophosphorylation. Blocking this process and inhibiting neovascularization is very attractive treatment ideas. Monoclonal antibodies and fusion protein drugs currently used in ophthalmology can bind free VEGF. In addition, there are also macromolecular antibodies binding VEGFR2 and small molecule tyrosine kinase inhibitors, which is expected to further expand into the field of ophthalmology. Although anti-VEGFR2 therapy is a revolutionary method to inhibit neovascularization, there are no sufficient clinical evidences at present. In-depth understanding of the application status and progress of anti-VEGFR2 in the treatment of retinal neovascular diseases has important clinical significance.
Diabetic macular edema (DME) is the most threatening complication of diabetic retinopathy that affects visual function, which is characterized by intractability and recurrent attacks. Currently, the clinical routine treatments for DME mainly include intravitreal injection, grid laser photocoagulation in the macular area, subthreshold micropulse laser, periocular corticosteroid injection, and vitrectomy. Although conventional treatments are effective for some patients, persistent, refractory, and recurrent DME remains a clinical challenge that needs to be urgently addressed. In recent years, clinical studies have found that certain combination therapies are superior to monotherapy, which can not only restore the anatomical structure of the macular area and effectively reduce macular edema but also improve visual function to some extent while reducing the number of treatments and the overall cost. This makes up for the shortcomings of single treatment modalities and is highly anticipated in the clinical setting. However, the application of combination therapy in clinical practice is relatively short, and its safety and long-term effectiveness need further exploration. Currently, new drugs, new formulations, and new therapeutic targets are still under research and development to address different mechanisms of DME occurrence and development, such as anti-vascular endothelial growth factor agents designed to anchor repetitive sequence proteins with stronger inhibition of vascular leakage, multiple growth factor inhibitors, anti-inflammatory agents, and stem cell therapy. With the continuous improvement of the combination application of existing drugs and treatments and the development of new drugs and treatment technologies, personalized treatment for DME will become possible.
Objective To evaluate the correlation of vascular endothelial growth factor (VEGF) and vascular endothelial cadherin (VE-Cadherin) in serum with the severity of obstructive sleep apnea (OSA) and explore their clinical value in OSA. Methods A total of 90 patients with OSA admitted to the Sleep Monitoring Center of the Affiliated Hospital of Xuzhou Medical University from April 2023 to June 2024 were prospectively selected. Based on the apnea-hypopnea index (AHI), the patients were divided into a mild group (5 - 15 times/hour, n=30), a moderate group (>15 - 30 times/hour, n=28), and a severe group (>30 times/hour, n=32). Thirty healthy individuals who underwent physical examinations during the same period were included as a control group. The levels of serum VEGF and soluble VE-Cadherin (sVE) in all subjects were detected by enzyme-linked immunosorbent assay. The differences in serum VEGF and sVE levels among the groups were compared, and the correlations between serum VEGF and sVE levels and sleep parameters were explored. The moderate and severe OSA patients were given 3 months of continuous positive airway pressure (CPAP) treatment, and the changes in sleep parameters and serum VEGF and sVE levels before and after treatment were compared. Results The levels of serum VEGF and sVE in the OSA patients increased with the severity of the disease; the levels of serum VEGF and sVE in the moderate and severe OSA groups were significantly higher than those in the healthy control group and the mild OSA group (P<0.05). The levels of serum VEGF and sVE in the severe OSA group were significantly higher than those in the moderate OSA group (P<0.05). There was no significant difference in the expression levels of serum VEGF or sVE between the mild OSA group and the healthy control group (P>0.05). The sensitivity and specificity of serum VEGF in diagnosing OSA were 65.6% and 93.3%, respectively, with an area under curve (AUC) value of 0.845. The sensitivity and specificity of serum VE-Cadherin in diagnosing OSA were 64.4% and 96.7%, respectively, with an AUC value of 0.835. After 3 months of CPAP treatment, AHI, longest apnea time, serum VEGF and sVE levels in the moderate and severe OSA groups decreased significantly, mean arterial oxygen saturation and lowest arterial oxygen saturation increased significantly (P<0.05). Conclusions The levels of VEGF and VE-Cadherin in serum of OSA patients are significantly elevated and positively correlated with the severity of OSA. Monitoring the changes in the levels of VEGF and VE-Cadherin in serum of OSA patients is helpful for evaluating the therapeutic effect of CPAP.