Anti-vascular Endothelial Growth Factor Agents Research Articles

Do intravitreal anti-vascular endothelial growth factor agents lead to renal adverse events? A pharmacovigilance real-world study.

Intravitreal vascular endothelial growth factor (VEGF) blockade is essential in many macular edema diseases treatment. However, intravitreal VEGF treatment has been reported to lead to deteriorated proteinuria and renal function. This study aimed to explore the relationship between renal adverse events (AEs) and the intravitreal use of VEGF inhibitors. In the FDA's Adverse Event Reporting System (FAERS) database, we searched for renal AEs of patients receiving various anti-VEGF drugs. We performed statistics on renal AEs in patients treated with Aflibercept, Bevacizumab, Ranibizumab, and Brolucizumab (from January 2004 to September 2022) using disproportionate and Bayesian analysis. We also investigated the time to onset, fatality, and hospitalization rates of renal AEs. We identified 80 reports. Renal AEs were most frequently associated with Ranibizumab (46.25%) and Aflibercept (42.50%). However, the association between intravitreal anti-VEGFs and renal AEs was insignificant since the reporting odds ratio of Aflibercept, Bevacizumab, Ranibizumab, and Brolucizumab were 0.23 (0.16, 0.32), 0.24 (0.11, 0.49), 0.37 (0.27, 0.51) and 0.15 (0.04, 0.61), respectively. The median time to renal AEs onsets was 37.5 (interquartile range 11.0-107.3) days. The hospitalization and fatality rates in patients who developed renal AEs were 40.24 and 9.76%, respectively. There are no clear signals for the risk of renal AEs following various intravitreal anti-VEGF drugs based on FARES data.

Treatment of neovascular age-related macular degeneration within 48 h from diagnosis improves long-term functional outcome

PurposeTo evaluate long-term visual and anatomical outcomes in neovascular age-related macular degeneration (nAMD) patients treated with anti-vascular endothelial growth factor (VEGF) agents depending on the time delay from confirmed diagnosis to treatment initiation. Materials and methodsSeventy-three nAMD patients (73 eyes) treated with anti-VEGF agents for 12 months using the pro re nata regimen were included in this retrospective longitudinal study. Patients were split into 3 groups according to the time from diagnosis to first anti-VEGF injection: < 48 h (group 1); 48 h-7 days (group 2); > 7 days (group 3). Decimal best-corrected visual acuity (VA) and macular thickness (MT) were recorded at baseline and 1–2-, 3–4-, 6- and 12-month later. Furthermore, age, gender as well as the applied treatment and number of injections after 12 months of treatment were also registered and compared. ResultsLong-term effect of the treatment demonstrated enhanced VA in group 1 patients compared with the rest of groups after 1–2-, 6-, and 12-month follow-up (P < 0.05). Positive effects of early treatment were additionally corroborated by the augmented percentage of patients with normal VA in the group 1 respect to the rest of groups over studied time points (P < 0.05). Moreover, the VA gain in nAMD at group 1 was obtained with a mean of 3.7 intravitreal injections over 1-year follow-up period. Regarding MT, non-significant difference was observed among groups. ConclusionsAn early initial treatment with VEGF inhibitors is critical to achieve the best functional benefits of this therapy in new-onset nAMD patients.

Systemic Cytokines in Retinopathy of Prematurity

Retinopathy of prematurity (ROP), a vasoproliferative vitreoretinal disorder, is the leading cause of childhood blindness worldwide. Although angiogenic pathways have been the main focus, cytokine-mediated inflammation is also involved in ROP etiology. Herein, we illustrate the characteristics and actions of all cytokines involved in ROP pathogenesis. The two-phase (vaso-obliteration followed by vasoproliferation) theory outlines the evaluation of cytokines in a time-dependent manner. Levels of cytokines may even differ between the blood and the vitreous. Data from animal models of oxygen-induced retinopathy are also valuable. Although conventional cryotherapy and laser photocoagulation are well established and anti-vascular endothelial growth factor agents are available, less destructive novel therapeutics that can precisely target the signaling pathways are required. Linking the cytokines involved in ROP to other maternal and neonatal diseases and conditions provides insights into the management of ROP. Suppressing disordered retinal angiogenesis via the modulation of hypoxia-inducible factor, supplementation of insulin-like growth factor (IGF)-1/IGF-binding protein 3 complex, erythropoietin, and its derivatives, polyunsaturated fatty acids, and inhibition of secretogranin III have attracted the attention of researchers. Recently, gut microbiota modulation, non-coding RNAs, and gene therapies have shown promise in regulating ROP. These emerging therapeutics can be used to treat preterm infants with ROP.

Consequences of Real-World Surveillance of Fellow Eyes in Neovascular Age-Related Macular Degeneration.

This study investigated whether the interval of monitoring at-risk, fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD) has any bearing on the severity of the disease at the time of diagnosis. The study comprised a retrospective, cross-sectional comparative case series of treatment-naïve eyes in patients who were diagnosed sequentially with nAMD. We compared the visual acuity (VA) and central macular thickness (CMT) of patients who were actively receiving intravitreal injections (IVIs) of anti-vascular endothelial growth factor (anti-VEGF) agents at the time of second eye diagnosis with the VA and CMT of patients who had ceased treatment in their first eye because of reaching end-stages of disease. Intervals of visits and frequency of monitoring the macula of fellow eyes by means of optical coherence tomography (OCT) were abstracted from the medical record. We found that the at-risk fellow eyes of patients who had stopped treatment for nAMD in their first eye prior to fellow eye conversion were monitored significantly less frequently than the fellow eyes of patients who continued to receive treatment at the time of second eye diagnosis. Despite less frequent monitoring, VA and CMT were similar at the time of fellow eye diagnosis for both groups.

Short-term effects of intravitreal anti-vascular endothelial growth factor agents on body weight and multiple systems after treatment for retinopathy of prematurity.

This study's goal was to assess the short-term effect on body weight and multiple systems following intravitreal injections of ranibizumab and aflibercept for retinopathy of prematurity (ROP). We retrospectively assessed infants with ROP who received intravitreal anti-vascular endothelial growth factor agents (VEGF) treatment at our hospital. They were classified into 2 groups based on the drugs administered: the intravitreal ranibizumab (IVR) group and the intravitreal aflibercept (IVA) group. The body weight (BW) gains for the pre-treatment week, the 1st week after treatment, and the 2nd week after treatment were compared for each group. Additionally, other parameters such as blood pressure, heart rate, oxygen concentration, volume of milk and output of urine at four time points were also measured. We used repeated measurement analysis of variance analyzed these data. In total, 95 preterm infants were recruited, including 51 cases in the IVR group and 44 cases in the IVA group. The BW gain for the 1st week after treatment was significantly lower than the pre-treatment week in each group (P < 0.05), while there was no decrease in weekly BW gain in the 2nd week after treatment compared with that pre-treatment week. Based on the comparison between groups, the BW gain in the IVR group was significantly higher than in the IVA group in the second post-treatment week. Repeated measurement analysis of variance showed that there were no significant differences in blood pressure, heart rate, oxygen concentration, volume of milk and output of urine in both groups over time. IVR and IVA could have a short-term inhibitive effect on body weight gain in infants after treatment for ROP, whereas there is no significant impact on other systems.

Reduced Size of Telangiectatic Capillaries After Intravitreal Injection of Anti-Vascular Endothelial Growth Factor Agents in Diabetic Macular Edema

Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents reduces microaneurysms in patients with diabetic macular edema (DME). However, residual anti-VEGF-resistant telangiectatic capillaries (TelCaps) have been reported. In this study, we investigated changes in the size of TelCaps after intravitreal injection of anti-VEGF agents in DME. Indocyanine green angiography (IA) and optical coherence tomography were performed before and 3 months after the intravitreal injection of anti-VEGF agents (pro re nata regimen after three monthly loading doses) in 12 eyes of 12 patients (7 males and 5 females, mean age 65.2 ± 8.8 years) with DME. The number and size of TelCaps within a 6-mm diameter macular region of the edema were measured using optical coherence tomography B-scan images overlaid on IA images. There were significant reductions in the number and size of TelCaps between the baseline and 3 months after anti-VEGF agent administration (P < 0.05 and P < 0.0001, respectively). The maximum corrected visual acuity (logMAR visual acuity) and the central macular thickness after anti-VEGF therapy were significantly improved (P < 0.01 and P < 0.02, respectively). The TelCaps remaining after loading three consecutive anti-VEGF agents had a significantly larger mean size at baseline than the TelCaps that resolved after the treatment (P < 0.03). Our study demonstrated that intravitreal injection of anti-VEGF agents could reduce TelCap size in patients with DME. We propose that larger-sized TelCaps detected by IA might be useful predictors of refractory DME, which could thus be principal targets of laser photocoagulation.

High-dose Aflibercept with Increased Dosing Intervals as a New Standard of Care for DMO and nAMD

The introduction of vascular endothelial growth factor inhibitors has led to significant improvements for patients with neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO). Landmark trials – such as ANCHOR, MARINA and VIEW for nAMD and RIDE/RISE, VIVID and VISTA for DMO – showed positive results, including clinically meaningful gains in Early Treatment Diabetic Retinopathy Study letters, with anti-vascular endothelial growth factor agents now the standard of care for nAMD and DMO. More recent studies, including those investigating high-dose aflibercept in nAMD and DMO, have focused on durability of response by studying increased treatment intervals to reduce the treatment burden on patients and physicians alike. The PULSAR (nAMD) and PHOTON (DMO) trials included high-dose (8 mg) aflibercept at either 12-week or 16-week dosing intervals and showed non-inferior visual gains compared with the standard dose of 2 mg, with ≥83% of patients maintaining their extended dosing interval throughout the 48-week studies. This is certainly an exciting development, and it will be interesting to see how extended treatment durability will impact management paradigms for patients with nAMD and DMO.

A Systematic Review and Meta-Analysis of Clinical Outcomes of Small Gauge Vitrectomy with or without Intravitreal Anti-Vascular Endothelial Growth Factor Agents Pretreatment for Proliferative Diabetic Retinopathy

Background: Proliferative diabetic retinopathy (PDR) is a common visual threatening ocular disease, patients with nonclearing vitreous hemorrhage (VH), tractional retinal detachment (RD), or extensive fibrovascular proliferation are always in need for surgical treatment. Although several studies reported better surgical outcome in patients underwent surgery after anti-VEGF injection, the effect of anti-VEGF pretreatment for small gauge vitrectomy in PDR patients remains to be elucidated. Objectives: The objective of the study was to evaluate the benefits of preoperative anti-VEGF treatment in small gauge vitrectomy for PDR patients. Methods: A comprehensive literature search in PubMed, Embase, and the Cochrane Central Register of Controlled Trials was performed to identify relevant studies. Meta-analyses were performed for intraoperative (including intraoperative bleeding, endodiathermy, iatrogenic retinal breaks, surgical time, etc.) and postoperative outcome parameters (including best-corrected visual acuity (BCVA), postoperative VH, postoperative RD, etc.). Results: Ten randomized controlled trials were identified and used for comparing small gauge vitrectomy alone (344 eyes, control group) and small gauge vitrectomy with preoperative anti-VEGF injection (355 eyes). The intraoperative findings showed that the surgical time, the incidence of clinically significant intraoperative bleeding, iatrogenic retinal breaks, silicone oil tamponade, and the frequency of endodiathermy were significantly less in the anti-VEGF pre-treated group than in the vitrectomy alone group (p < 0.01). The postoperative findings showed that the incidences of early postoperative VH, postoperative RD were significantly less in the anti-VEGF pre-treated group than in the control group (p < 0.05). The pooled result of postoperative rubeosis iridis/neovascular glaucoma was borderline (p = 0.072) between cases and controls, while no statistically significant differences in BCVA at last follow-up and incidences of late postoperative VH were found between these two groups (p > 0.05). Conclusions: Anti-VEGF injection prior to small gauge vitrectomy in PDR patients might facilitate easier surgical procedure and reduce intra- and postoperative complications. Further studies are needed to verify our findings and evaluate the optimal interval and dosage for preoperative anti-VEGF injection.

Intake of &lt;i&gt;Lactobacillus Pentosus TJ515&lt;/i&gt; Prevents the Formation of Retinal Edema in Retinal Vein Occlusion Model Mice

Macular edema is a sight-threatening symptom in patients with retinal vein occlusion (RVO) and diabetic retinopathy. It is treated by the intravitreal injection of anti-vascular endothelial growth factor agents, but this has a physical burden on patients. Thus, it is important to develop a treatment that can be administered orally. The probiotic Lactobacillus pentosus TJ515 can reduce inflammation by regulating host immunity via its induction of interleukin-10 (IL-10). However, its action on inflammatory diseases of the retina remains unclear. This study aimed to investigate the preventive effects of L. pentosus TJ515 intake on retinal edema using RVO model mice. Occlusion of the retinal vein led to an increase in the thickness of all retinal layers and the inner nuclear layer. Intake of L. pentosus TJ515 for three weeks suppressed the formation of retinal edema versus vehicle and the control strain (L. pentosus JCM1558). The expression of MCP-1 and MCP-3 was increased in RVO model mice but suppressed by the intake of L. pentosus TJ515. F4/80-positive cells (i.e., activated macrophages) were increased in the retinas of RVO model mice but decreased by the intake of L. pentosus TJ515. Therefore, L. pentosus TJ515 suppressed macrophage migration in the retinas. Treatment of mouse bone marrow-derived macrophages (BMDM) with plasma from mice that had ingested L. pentosus TJ515 decreased the mRNA expression of IL-6 and increased the mRNA expression of IL-10. Thus, oral intake of L. pentosus TJ515 can prevent retinal edema through its anti-inflammatory effects on macrophages and inhibiting effects on macrophage migration.

Comparison of Dexamethasone Implant and Anti-VEGF Agents in the Treatment of Naive Diabetic Macular Oedema: A Prospective Cohort Study

Introduction: Diabetic Retinopathy (DR) is one of the common microvascular complications of diabetes. In patients with DR, the most frequent cause of vision loss is Diabetic Macular oedema (DME). In the present era, anti-Vascular Endothelial Growth Factor (anti-VEGF) agents are the mainstay of treatment for managing DME. A majority of patients show a good response to multiple doses of these agents administered by a pro re nata regimen at regularly spaced fixed intervals. However, the tendency of DME to become chronic and resistant to these agents, as well as the burden of repeated injections, necessitates considering alternative treatment options with similar or better efficacy. As steroids can address these drawbacks of anti-VEGF treatment, the present study compared the efficacy of anti-VEGF agents with dexamethasone implant in the treatment of naïve DME. Aim: To compare the effectiveness of dexamethasone implant with anti-VEGF agents in the treatment of naïve DME. Materials and Methods: A prospective cohort study was conducted in the Department of Ophthalmology at Kalinga Institute of Medical Sciences and Pradyumna Bal Memorial Hospital, Bhubaneswar, Odisha, India from September 2020 to September 2022. A total of 100 eyes with DME, newly diagnosed patients aged 18 years and above, without other macular oedema-causing diseases, were included. A total of 50 eyes in each group were treated with an anti-VEGF agent (Group A) or dexamethasone implant (Group B), and Best Corrected Visual Acuity (BCVA) and Central Foveal Thickness (CFT) were monitored for six months. For statistical analysis, paired t-test and independent t-test were used for within-group and inter-group analysis, respectively. A p-value &lt;0.05 was considered statistically significant. Results: In both groups, post-treatment BCVA showed marked improvement, but there was no significant difference in mean BCVA between the groups (p=0.89) at six months. However, the mean CFT showed significant improvement in Group B at six months. In Group A, the mean CFT reduced from 441.87±54.48 μm to 257.83±25.73 μm, and in Group B, the mean CFT reduced from 464±109.44 μm to 207±22.51 μm at six months (p&lt;0.0001). Adverse events like cataracts and glaucoma were seen in patients treated with the dexamethasone implant and were managed by cataract surgery and topical anti-glaucoma medications, respectively. Conclusion: Dexamethasone implant and anti-VEGF agents are equally effective in improving visual acuity; however, dexamethasone stands superior in reducing macular thickness. Needing fewer injections while treating with a dexamethasone implant improves compliance. The progression of cataract remains a major side-effect with the dexamethasone implant, which is not a concern when treating DME in pseudophakic eyes.

Subfoveal choroidal thickness before and after intravitreal Ranibizumab injection in patients with choroidal neovascularization

Background: Ranibizumab is anti-vascular endothelial growth factor (anti-VEGF) agent made for intraocular use, like smaller antibody fragment that can penetrate retina. Intravitreal ranibizumab therapy has been accepted as a predominant treatment for CNV in recent years.

Radiation retinopathy following episcleral brachytherapy for intraocular tumors: Current treatment options.

Radiation retinopathy (RR) and radiation maculopathy (RM) can occur as a result of uveal melanoma radiation treatment and after irradiation of other head and neck extraocular tumors, even with precise targeting techniques, such as stereotactic or proton beam radiotherapy. This review provides an overview of the current understanding of potential radiation damage to ocular tissues, and how recent developments in ophthalmic multimodal imaging techniques and treatment modalities have improved managing options. Several treatment strategies have been employed so far for the management of RR, including laser photocoagulation, intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents or glucocorticosteroids and surgery. The use of intravitreal anti-VEGFs or dexamethasone implants have significantly altered the final visual outcome for uveal melanoma patients. As a prophylaxis, a few different strategies were proposed, but still there is a lack of large randomized clinical trials supporting these approaches and clear clinical guidelines for daily practice. Early detection and proper treatment are crucial in preventing or reducing vision loss, and improving patients' quality of life. Close monitoring and timely intervention are essential for successful management.

Chinese Herbal Medicine Combined with Intravitreal Antivascular Growth Factor Agents in Treatment of Macular Edema Secondary to Retinal Vein Occlusion: A Systematic Review and Meta-Analysis.

Retinal vein occlusion (RVO) is the second most common retinal vascular disease in the world after diabetic retinopathy. Moreover, macular edema (ME) is the main cause of visual impairment in RVO patients. Intravitreal injection of antivascular endothelial growth factor (VEGF) agents is recommended for RVO-ME. However, repeated injections severely limit their efficacy. Chinese herbal medicine (CHM) is widely used in RVO-ME as adjuvant therapy in China. The study aims to evaluate the efficacy and safety of anti-VEGF combined with CHM for RVO-ME and to provide reliable evidence for clinical application. Seven databases were searched without language or publication status restrictions. Randomized controlled trials (RCTs) comparing anti-VEGF combined with CHM (anti-VEGF + CHM) versus anti-VEGF in participants with RVO-ME were included in this study. The "risk of bias assessment tool" of the Cochrane Handbook was applied to assess the quality of included trials, and RevMan 5.3 software was used for data analysis. A total of 10 relevant trials with 743 patients were identified. The results showed that BCVA of the anti-VEGF + CHM group significantly improved at 3 months (P < 0.00001), 6 months (P=0.008), and 12 months (P=0.01), and CMT significantly reduced at 1 month (P=0.02), 2 months (P=0.0009), 3 months (P < 0.05), 6 months (P < 0.0001), and 12 months (P < 0.00001) compared with the anti-VEGF group alone. At the same time, the anti-VEGF + CHM group has a better performance in reducing the number of injections (P < 0.05) and improving the total effective rate (P < 0.0001). However, regarding adverse events, there was no statistical difference between the two groups (P=0.09). Our results provide promising evidence that anti-VEGF therapy combined with CHM may be more beneficial to patients than anti-VEGF therapy alone. However, because of the low quality and small sample size of the included studies, more rigorous and larger-scale trials were necessary to validate our results. Registration Number. CRD42021270262.

Роль блокады ангиогенеза у пациентов с диабетической ретинопатией

Relevance. The proliferative stage of diabetic retinopathy is characterized by angiogenesis, which is largely mediated by the vascular endothelial growth factor. Peripheral retinal laser coagulation has been standard treatment for PDR for many years, providing control of ischemia and reduction of vascular endothelial growth factor levels with subsequent regression of neovascularization. However, it leads to serious functional deficits and anatomical complications. The advent of antivascular endothelial growth factor (anti-VEGF) agents has changed the future of PDR management and has provided an alternative to pan retinal photocoagulation. Their combination with panretinal photocoagulation may be effective for the treatment of proliferative diabetic retinopathy and concurrent diabetic macular edema. Anti-VEGF therapy also takes place in surgery of complicated PDR. Purpose. To analyze the relevance of the use of anti-VEGF drugs in the treatment of the proliferative stage of diabetic retinopathy. Material and methods. The literature review is written using PubMed, Сochrane Library, 29 literature references published up to 2021. Results. In patients with severe cases, preoperative treatment is a gentle approach for the anatomic structures of the eye, it also contributes to the reduction in the number of intraoperative and postoperative complications. Conclusion. Preoperative treatment is a gentle approach for the anatomic structures of the eye, it also contributes to the reduction in the number of intraoperative and postoperative complications. Key words: anti-VEGF, diabetic macular edema, proliferative diabetic retinopathy.

The Patient Voice in Neovascular Age-Related Macular Degeneration: Findings from a Qualitative Study.

Visual impairment resulting from diseases such as neovascular age-related macular degeneration (nAMD) may cause behavioural, environmental, psychological, and logistical challenges that could act as barriers to effective uptake and sustainability of treatment with anti-vascular endothelial growth factor agents (anti-VEGFs). Understanding emotions and experiences of patients with nAMD may help inform the determinants of adherence, and could contribute to improvements in ophthalmic outcomes and quality of life. Seventeen patients with nAMD receiving anti-VEGF injections were enrolled from three clinics: one each in France (n = 5), Germany (n = 6), and the UK (n = 6). Patients' health information and treatment characteristics were collected. Individual phone interviews were conducted by experienced health care interviewers. Transcripts were analysed thematically. Patients (53% female) had a mean age of 77years. Bilateral anti-VEGF injections were received by 24% (n = 4); and most (76%, n = 13) were adherent to their treatment. Patient emotions at diagnosis ranged from happiness at learning about the treatment for nAMD to being terrified of receiving an injection in the eye. Most patients mentioned feeling anxious and fearful before their first injection despite receiving reassurance. After the first injection, these feelings and apprehension abated for many, but not all. With the goal of maintaining the best possible vision, few (24%, n = 4) patients reported more than one missed appointment, and most had never considered stopping treatment. No patient reported additional assistance beyond family support; however, many had difficulties with recreational and domestic activities and had developed coping strategies. This study provides insights on patients' emotions related to their experience of nAMD and its management, highlighting the varying experiences between individuals. It shows the importance of the patient's voice when considering patient care and management, and how the nature and timing of interventions can improve the experience of living with and managing nAMD.

Evaluation of short-term intraocular pressure changes after intravitreal injection of Conbercept in patients with diabetic macular edema.

Background: The study concerning the influence of Conbercept, which is an anti-Vascular endothelial growth factor (VEGF) agent, in intraocular pressure (IOP) spike is limited and warrants further investigation. The current study aimed to investigate the changes of intraocular pressure after intravitreal injection (IVI) of Conbercept and evaluate the risk factors associated with intraocular pressure spikes. Methods: Patients with diabetic macular edema receiving intravitreal injection of 0.05ml (0.5mg) Conbercept were involved in the study. All patients underwent slit lamp examination to determine the status of phakia/pseudophakia. The axial length was measured using IOL Master 500 before intravitreal injection. Patients underwent a Conbercept intravitreal injection with a 30-gauge needle in a standard fashion. The intraocular pressure was measured 2min before injection, and 2, 10, 30min, 1, 2, 5, 24h after injection using a rebound tonometer. The changes of intraocular pressure and the relevant risk factors were evaluated. Patients were subdivided into phakic group and pseudophakic group to analyze the effect of lens status on intraocular pressure changes. Results: Forty patients with a mean age of 62.48 ± 12.22 years were included in the study. The mean intraocular pressure values at baseline and 2, 10, 30min, 1, 2, 5, 24h after injection were 14.81 ± 3.13mmHg, 26.80 ± 9.43mmHg, 18.76 ± 6.16mmHg, 16.54 ± 5.94mmHg, 15.64 ± 3.75mmHg, 14.46 ± 3.03mmHg, 14.10 ± 1.88mmHg, 14.23 ± 2.71mmHg respectively. The intraocular pressure after injection for 2, 10min was significantly higher than baseline (p < 0.001, p = 0.001, respectively). The intraocular pressure between baseline and post-injection for 30min or beyond were comparable (all p > 0.05). No significant difference was found between the phakic group and pseudophakic group (p = 0.422). The changes of intraocular pressure were positively correlated with age (r = 0.329, p = 0.038), but negatively with axial length (r = -0.472, p = 0.002). Conclusion: intravitreal injection of Conbercept may cause rapid spike of intraocular pressure, but is safe with respect to short-term changes. The intraocular pressure in patients with older age and shorter axial length is more likely to be higher after intravitreal injection.

Suppression of Pathological Ocular Neovascularization by a Small Molecular Multi-Targeting Kinase Inhibitor, DCZ19903.

The administration of anti-vascular endothelial growth factor agents is the standard firs-line therapy for ocular vascular diseases, but some patients still have poor outcomes and drug resistance. This study investigated the role of DCZ19903, a small molecule multitarget kinase inhibitor, in ocular angiogenesis. The toxicity of DCZ19903 was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assays, flow cytometry, Calcein-AM/PI staining, and terminal uridine nick-end labeling staining. Oxygen-induced retinopathy and laser-induced choroidal neovascularization models were adopted to assess the antiangiogenic effects of DCZ19903 by Isolectin B4 (GS-IB4) and hematoxylin-eosin staining. EdU assays, transwell migration assays, tube formation, and choroid sprouting assays were performed to determine the antiangiogenic effects of DCZ19903. The antiangiogenic mechanism of DCZ19903 was determined using network pharmacology approach and western blots. There was no obvious cytotoxicity or tissue toxicity after DCZ19903 treatment. DCZ19903 exerted the antiangiogenic effects in OIR model and choroidal neovascularization model. DCZ19903 inhibited the proliferation, tube formation, migration ability of endothelial cells, and choroidal explant sprouting. DCZ19903 plus ranibizumab achieved greater antiangiogenetic effects than DCZ19903 or ranibizumab alone. DCZ19903 exerted its antiangiogenic effects via affecting the activation of ERK1/2 and p38 signaling. DCZ19903 is a promising drug for antiangiogenic treatment in ocular vascular diseases. These findings suggest that DCZ19903 possesses great antiangiogenic potential for treating ocular vascular diseases.

SPATIAL PATTERN OF RETINAL PIGMENT EPITHELIUM TEAR DEVELOPMENT AND PROGRESSION AFTER ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

The aim of this study was to demonstrate the spatial pattern of retinal pigment epithelium (RPE) tear development and progression after antivascular endothelial growth factor therapy for neovascular age-related macular degeneration. We retrospectively reviewed six eyes with neovascular age-related macular degeneration that showed RPE tears after administration of intravitreal antivascular endothelial growth factor agents and were followed up for 12 months. The patterns of RPE tear development and progression were evaluated by analyzing positional relationships among the locations of the choroidal neovascularization membrane and pigment epithelial detachment (PED) area at baseline and the tear area using spectral-domain optical coherence tomography, color photography, fluorescein angiography, and fundus autofluorescence images. Pretear OCT images revealed fibrovascular PED in all eyes, one of which showed complications of hemorrhagic PED after treatment. In five eyes, RPE tears developed at the PED edge located on the opposite side of the choroidal neovascularization membrane. In the eye showing hemorrhagic PED, the RPE tear developed along the wide area of the PED edge. The torn RPE monolayer contracted toward the side of the choroidal neovascularization membrane in all eyes, and RPE loss involved the fovea in five eyes that showed significantly worse visual acuity (VA) after 12 months in comparison with the baseline value before the tear (logMAR VA; 0.3 vs. 1.29; P < 0.02). The location of choroidal neovascularization membrane in PED determines the spatial pattern of RPE tear development and progression and helps to predict the visual outcome after RPE tears.

Retinopathy of prematurity.

Retinopathy of prematurity (ROP) is a devastating neurovascular disease of the retina in newborn infants that can lead to vision deficits or even blindness. In this concise review we discuss our current knowledge about diagnosis, etiology, pathogenesis, intervention, and outcomes of the disease. Major advancements have been made both in categorizing the disease in the new International Classification of Retinopathy of Prematurity, Third Edition classification and in treating severe ROP with anti-vascular endothelial growth factor (VEGF) agents. New development always creates new questions and opens up new areas of research. We will discuss in this review both the benefits and downsides of the new anti-VEGF treatment approaches in ROP, especially in light of our improved understanding of the underlying ROP pathophysiology. We also offer pointers to areas where more research is needed. WHAT THIS PAPER ADDS: Concise update on all aspects of retinopathy of prematurity (ROP), including advances in understanding and treatment. Benefits and risks of the new treatment method of anti-vascular endothelial growth factor injections in ROP are discussed. New research areas that deserve attention in the coming years are identified.

Real-world outcomes of anti-vascular endothelial growth factor therapy for retinal vascular vein occlusion in Tibet, China.

To evaluate the outcomes of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents for patients with retinal vein occlusion (RVO) related-macular edema (ME) in Tibetan. A retrospective, observational, single-center study. The demographic and clinical data of 90 RVO Tibetan patients (93 eyes) treated with either ranibizumab or conbercept in Tibet Autonomous Region People's Hospital from Jan 2018 to December 2019 were collected. The mean patient age was 56.8±10.6y, 45 (50%) of them were female. The mean living altitude was 3867.8±567.9 m. At the last visit, the best-corrected visual acuity (BCVA) significantly increased (52.2±21.8 letters) in comparison with the baseline (38.2±24.1 letters, P<0.001); while the central retinal thickness (CRT) significantly reduced (245.5±147.6 µm) in comparison with the baseline (504.1±165.2 µm, P<0.001). The 43.0% of the eyes gained ≥15 letters, 60.2% of the eyes gained ≥10 letters, and 78.5% of the eyes gained ≥5 letters. No vision loss was noted in 92.5% of the eyes, 4 eyes lost more than 10 letters during follow-up period. The mean number of injections was 2.4±1.8. No severe ocular or systemic adverse events related to either the drug or injection were noted. Anti-VEGF therapy is effective and safe in Tibetan patients for the treatment of RVO related ME.