Anti-vascular Endothelial Growth Factor Research Articles

The analysis of foveal microvascular anomalies in retinopathy of prematurity after anti-vascular endothelial growth factor therapy using optical coherence tomography angiography

The analysis of foveal microvascular anomalies in retinopathy of prematurity after anti-vascular endothelial growth factor therapy using optical coherence tomography angiography

Efficacy of intravitreal faricimab therapy for polypoidal choroidal vasculopathy: A systematic review and meta-analysis.

Polypoidal choroidal vasculopathy (PCV) is an aneurismal type of macular neovascularization that show similarities with age-related macular degeneration and diseases that are part of the pachychoroid disease spectrum. Exudative changes in PCV can be treated with intravitreal anti-vascular endothelial growth factor monotherapy; however, a combination therapy with photodynamic therapy may be required. In this systematic review and meta-analysis, we evaluated the efficacy of faricimab for PCV. We searched 12 literature databases for eligible studies. All study evaluation and data extraction were made by two authors in duplicate. Studies eligible for analysis were included for a qualitative and quantitative review. We identified seven studies with data from 150 eyes with PCV, five studies were of treatment-naïve eyes who were commenced in faricimab monotherapy, and two studies were of switch-over to faricimab from other anti-VEGF drugs. After faricimab loading dose in treatment-naïve eyes, the best-corrected visual acuity (BCVA) remained stable at -0.09 (95% CI: -0.20-0.03) logMAR, central retinal thickness (CRT) decreased -169 (95% CI: -311--27) μm, and 48.7 (95% CI: 32.5-65.0) % of eyes obtained polyp closure. In switch-over eyes, 57%-67% experienced fluid reduction and 21% were able to extend their treatment interval. In conclusion, faricimab monotherapy for PCV leads to acceptable clinical outcomes in terms of stable BCVA, reduction of CRT, and high incidence of polyp closure. Some cases may benefit from a switch to faricimab. However, long-term efficacy studies and controlled comparative studies are warranted.

Anti-VEGF treatment outcome prediction based on optical coherence tomography images in neovascular age-related macular degeneration using a deep neural network.

Age-related macular degeneration (AMD) is a major cause of blindness in developed countries, and the number of affected patients is increasing worldwide. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) are the standard therapy for neovascular AMD (nAMD), and optical coherence tomography (OCT) is a crucial tool for evaluating the anatomical condition of the macula. However, OCT has limitations in accurately predicting the degree of functional and morphological improvement following intravitreal injections. Artificial intelligence (AI) has been proposed as a tool for predicting the treatment response of nAMD based on OCT biomarkers. Our study focuses on the development and assessment of an AI model utilizing the DenseNet201 algorithm. The model aims to predict anatomical improvement based on OCT images before, and during anti-VEGF therapy. The training process involves two scenarios: (1) using only preinjection OCT images and (2) utilizing both OCT images before and during anti-VEGF therapy for model training. The outcomes of our investigation, involving 2068 images from a cohort of 517 Korean patients diagnosed with nAMD, indicate that the AI model we introduced surpassed the predictive performance of ophthalmologists. The model exhibited a sensitivity of 0.915, specificity of 0.426, and accuracy of 0.820. Notably, its predictive capabilities were further enhanced with the inclusion of additional OCT images taken after the first and second injections during the loading phase. The treatment prediction performance of the model was the highest when using all input modalities (before injection, and after the first and second injections) and concatenation-based fusion layers. This study highlights the potential of AI in assisting individualized and tailored nAMD treatment.

Gadoxetic Acid-Enhanced Magnetic Resonance Imaging Features Can Predict Immune-Excluded Phenotype of Hepatocellular Carcinoma

Introduction: Immunotherapy is the first-line treatment for intermediate-advanced stage hepatocellular carcinoma (HCC), although its outcomes vary. This study aimed to identify imaging biomarkers of immunotherapy susceptibility linked to gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) and immune phenotypes, particularly immune-excluded phenotypes, with a tumor immune barrier. Methods: We performed immunohistochemical staining with a CD8+ antibody, and samples were classified into immune-inflamed, -intermediate, -excluded, and -ignored phenotypes. We assessed EOB-MRI findings obtained from 104 patients who underwent hepatectomy for HCC and evaluated the relationship between MRI findings and immune phenotype. Spatial transcriptome analysis of tumor tissues in each immune phenotype was performed to characterize the MRI findings. For validation, we analyzed the treatment effect on 60 nodules in another cohort of 27 patients who received combined immunotherapy using anti-programmed death-ligand 1 and anti-vascular endothelial growth factor (VEGF) antibodies. Results: HCCs with rim arterial phase hyperenhancement (APHE) (odds ratio [OR] 17.3 P=0.009), peritumoral enhancement on the arterial phase (OR 8.6, P<0.004), and intermediate intensity on the hepatobiliary phase (HBP) measured with a visual 3-point scale (OR 28.2, P=0.002) were associated with immune-excluded phenotype, where tumors tended to be larger and of the single nodular type with extranodular growth and confluent multinodular rather than the simple nodular type. Spatial transcriptome analysis revealed a spatial relationship among cytotoxic T lymphocytes, VEGF signals, and cancer-associated fibroblasts at the tumor-invasive margins in this phenotype. From the validation study, nodules with any one of these three imaging findings had a significantly prolonged time to-nodular progression (P=0.007, median not reached vs. 226 days). Conclusion: HCCs with rim APHE, peritumoral enhancement on arterial phase, and intermediate intensity on HBP with visual 3-point scale could be non-invasive biomarkers to predict the immune-excluded phenotype with tumor immune barrier. These HCCs were most likely to respond to the combined immunotherapy.

Short-term intraocular pressure changes after intravitreal aflibercept 2 mg, aflibercept 8 mg and faricimab: a prospective, comparative study

Background/aimsIntravitreal injection (IVT) of anti-vascular endothelial growth factor agents is the standard of care for several retinal diseases but can cause intraocular pressure (IOP) elevations. This study investigates short-term postinjection...

EXTH-04. COMBINATION OF BEVACIZUMAB ENHANCES THE ANTI-TUMOR EFFICACY OF AD-SGE-REIC FOR GLIOMA

Abstract Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is a tumor suppressor gene and its overexpression has been shown to exert anti-tumor effects as a therapeutic target gene in many human cancers. Recently, we revealed the anti-glioma effects of an adenoviral vector carrying REIC/Dkk-3 with the super gene expression system (Ad-SGE-REIC) and conducted the phase Ⅰ/Ⅱ a clinical trial for recurrent malignant glioma (jRCT2063190013). Anti-vascular endothelial growth factor treatments such as bevacizumab have demonstrated convincing therapeutic efficacy in patients with glioma. In this study, we examined the effects of Ad-SGE-REIC on glioma treated with bevacizumab in vitro and in vivo. Ad-SGE-REIC treatment resulted in a significant reduction in the number of invasion cells treated with bevacizumab. Western blot analyses revealed the increased expression of several endoplasmic reticulum stress markers in cells treated with both bevacizumab and Ad-SGE-REIC, as well as decreased β-catenin protein levels. In glioma-bearing mouse models, survival was extended in the combination therapy group. These results suggest that the combination therapy of Ad-SGE-REIC and bevacizumab showed anti-glioma effects by suppressing the angiogenesis and invasion of tumor cells. Combined Ad-SGE-REIC and bevacizumab might be a promising strategy for the treatment of malignant glioma.

Proton beam irradiation with anti-VEGF therapy for polypoidal choroidal vasculopathy: results of a 24-month, phase II randomized study.

To determine the efficacy and safety of proton beam irradiation (PBI) and anti-vascular endothelial growth factor (anti-VEGF) therapy for polypoidal choroidal vasculopathy (PCV)/ aneurysmal type 1 macular neovascularization (AT1). The randomized clinical trial consisted of newly diagnosed active PCV/AT1 patients who were randomized 1:1 to treatment with three initial monthly intravitreal anti-VEGF agent (conbercept) injections with or without single 14 GyE radiation. Subsequent anti-VEGF therapy was given pro re nata. The primary outcome measures were number of anti-VEGF injections, best-corrected visual acuity (BCVA), and central retinal thickness (CRT) at 24months. Secondary outcome measures included the polypoidal lesion regression rate, changes in the areas of polypoidal lesions and branching vascular network (BVN), and radiotherapy-related adverse events at 24months. A total of 45 eyes (86.5%) completed the 24-month follow-up. At 24months, the combination therapy group required fewer anti-VEGF injections compared with the monotherapy group (5.9 ± 4.1 vs. 8.8 ± 5.3; P = 0.04). The mean gains in BCVA and the mean decrease in CRT were not significantly different between the two groups (P = 0.85 and P = 0.17, respectively). Combination therapy was superior to monotherapy for complete polypoidal lesion regression (80.0% vs. 48%, P = 0.03) and change in BVN area (- 1.03 ± 1.24 mm2 vs. 0.36 ± 0.77 mm2, P < 0.01). The radiation-related microvascular abnormalities were observed in 55.0% of eyes following combination therapy at 15.7 ± 2.5months. PBI (14 GyE) combined with anti-VEGF therapy could decrease the need for additional anti-VEGF injections for PCV/AT1. Longer follow-up is needed to fully evaluate the long-term safety of PBI. What is known The current main methods for treating PCV/AT1 include anti-VEGF drugs as monotherapy or in combination with photodynamic therapy. However, some cases can be challenging with multiple repeated injections due to the relatively low regression rate of polyps and high recurrence rate. What is new Proton beam irradiation therapy with anti-VEGF drugs can synergistically promote the regression of polyps and the shrinkage of branching vascular network, and reduce the anti-VEGF treatment burden for patients with PCV/AT1. Radiation retinopathy was mild and did not appear to be visually significant at the 24-month follow-up. Proton beam irradiation can be a new strategy for the treatment of PCV/AT1.

Recurrence of Retinopathy of Prematurity Following Anti-vascular Endothelial Growth Factor (Anti-VEGF) Therapy: A Systematic Review and Meta-Analysis.

Retinopathy of prematurity (ROP) is a neovascular disorder which affects premature infantsand can lead to childhood blindness. Treatment includes laser photocoagulation and intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections, both effective options. However, laser photocoagulation can lead to refractive errors, while anti-VEGF therapy can result in disease recurrence. Our systematic review aimed to evaluate the recurrence rates of ROP following treatment with anti-VEGF agents compared to other anti-VEGF agents and laser photocoagulation. We also aimed to measure the retreatment intervals and assess successful retreatment rates to identify the most effectivetreatment modality. Our review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included both randomized controlled trials (RCTs) and non-randomized comparative studies (NCS). A thorough search of MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases was performed. Studies were assessed using the Cochrane Risk of Bias (RoB2) tool and the Newcastle-Ottawa Scale (NOS). Random-effects and fixed-effects models were used to measure pooled estimates. The outcomes were reported as risk ratios (RR) and standardized mean differences (SMD). A total of 21 studies (six RCTs and 15NCS) with 6,152 eyes were included. Overall, anti-VEGF agents showed a higher risk of recurrence compared to laser photocoagulation (RR=2.14, 95% CI: 1.06-4.33, p=0.03). Conbercept demonstrated a significantly lower risk of recurrence than laser photocoagulation and ranibizumab (RR=0.47, 95% CI: 0.39-0.58, p<0.00001), while aflibercept showed a higher recurrence risk compared to bevacizumab (RR=12.61, 95% CI: 6.43-24.73, p<0.00001). Bevacizumab was associated with a longer retreatment interval than laser photocoagulation (SMD=0.89, 95% CI: 0.61-1.17, p<0.00001). No significant differences in retreatment success rates between bevacizumab and laser photocoagulation were observed. Anti-VEGF therapy is effective in the treatment of ROP; however, it is associated with a higher risk of recurrence compared to laser photocoagulation. Conbercept shows greater efficacy in reducing recurrence risk and prolonging the retreatment interval compared to ranibizumab. Aflibercept demonstrated inconsistent outcomes. No significant difference in recurrence rates was observed between bevacizumab and ranibizumab. Recurrences occurred significantly later when anti-VEGF therapy was used compared to laser photocoagulation. Successful retreatment rates between bevacizumab and laser photocoagulation were similar.

Effect of Intravitreal Bevacizumab (Anti VEGF) Injection on Renal Function

Background: Vascular endothelial growth factor (VEGF) plays an important role in the development of both Proliferative Diabetic Retinopathy (PDR) &amp; Diabetic Macular Odema (DMO). An intravitreal anti-VEGF agent is an effective new modality of treatment. Some studies have dealt with systemic effects of intravitreal injection of anti-VEGF. However, decreasing renal function has been reported recently. Aims: To investigate the effect of intravitreal bevacizumab (anti VEGF) injection on renal function. Methods: This quasi-experimental study was carried out in the Department of ophthalmology, Bangabandhu Sheikh Mujib Medical University, Dhaka, during March 2019 to August 2021. A total of 40 patients with retinopathy treated with intravitreal injection bevacizumab were included in this study, out of which 20 patients having diabetic kidney disease (DKD) and rest 20 patients without diabetic kidney disease (No DKD). The patients having Diabetic Kidney Disease (DKD) whose Urinary Albumin Creatinine Ratio (UACR) &gt; 30 mg/g or Effective Glomerular Filtration Rate (eGFR) &lt; 60mL/min/1.73m2, No Diabetic Kidney Disease (No DKD) whose UACR &lt; 30 mg/g or eGFR &gt; 60mL/min/1.73m2. Patients of both sexes and age above 18 years were enrolled in this study. Pre- injection and 1 month after 3rd dose of intravitreal injection of bevacizumab, UACR, Serum Creatinine and eGFR were measured and compared. Results: It was observed that half (50.0%) of the patients in DKD and more than half (65.0%) in No DKD belonged to age group 50-59 years. Male was predominant in both the groups. The mean pre-injection of serum creatinine was 1.23±0.53 mg/dl in DKD and 0.87±0.22 mg/dl in No DKD. The mean post-injection of serum creatinine was 1.19±0.45 mg/dl in DKD and 0.87±0.16 mg/dl in No DKD. The mean pre-injection of UACR was 1294.9±968.26 mg/g in DKD and 13.8±5.99 mg/g in No DKD. The mean post-injection of UACR was 1142.11±1024.06 mg/g in DKD and 13.01±6.87 mg/g in No DKD. The mean difference of serum creatinine, eGFR and UACR were not significant (p&gt;0.05) between pre-injection and post-injection in both groups. Conclusion: Serum creatinine, eGFR and UACR were almost similar between pre-injection and post-injection in patients with diabetic kidney disease (DKD) and patients without diabetic kidney disease (No DKD).

Nonclinical Similarity of the Biosimilar Candidate ABP 938 with Aflibercept Reference Product.

ABP 938 is being developed as a biosimilar to Eylea® (aflibercept reference product [RP]), an anti-vascular endothelial growth factor (VEGF) drug used in the management of retinal diseases. Previously, a comparative analytical similarity assessment demonstrated that ABP 938 and aflibercept RP have the same amino acid sequence and exhibit similar higher-order structure and biological activity. The nonclinical studies described here were designed to assess the in vitro pharmacology and the in vivo pharmacokinetics (PK), toxicokinetics (TK), and safety profiles of ABP 938 compared to aflibercept RP. In vitro target-binding kinetics and affinity for VEGF-A and placental growth factor (PIGF) isoforms were evaluated using surface plasmon resonance (SPR). Effector functions were assessed by cell-based assays. PK was evaluated in a nonterminal intravitreal (IVT) ocular distribution study in rabbits. Safety was assessed in a 1-month IVT study in cynomolgus monkeys. SPR results demonstrated that ABP 938 is similar to aflibercept RP in binding kinetics and affinity for VEGF-A111, VEGF-A121, VEGF-A165, VEGF-A189, PlGF-1, and PlGF-2 isoforms. No antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, or complement-dependent cytotoxicity was observed with ABP 938 and aflibercept RP. Results from thenonterminal ocular distribution study in rabbits indicated that there were no meaningful differences in the distribution kinetics between intravitreally injected ABP 938 and aflibercept RP. Additionally, there was no evidence of ocular or systemic toxicity associated with IVT administration of ABP 938 in a repeat-dose, 1-month toxicology study in cynomolgus monkeys; toxicokinetic and toxicology profiles were similar to aflibercept RP. This integrated assessment of results from the in vitro pharmacology assessment and in vivo PK and TK/toxicology profiles formed the nonclinical portion of the totality of evidence demonstrating ABP938 is a biosimilar to aflibercept RP.

Comparison of eGFR Levels in Patients Before and After Intravitreal Bevacizumab (Anti-VEGF) Injection

Background: Estimated glomerular filtration rate (eGFR) is a vital indicator of kidney function, particularly in patients receiving treatments that may impact renal health, such as intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections like bevacizumab. Bevacizumab, commonly used to treat retinal diseases like diabetic retinopathy, has raised concerns about its potential systemic effects, including its impact on kidney function due to the role of VEGF in maintaining glomerular integrity. This study investigates the effect of bevacizumab injections on renal function in patients with diabetic kidney disease (DKD) and those without. Objective: To assess changes in eGFR before and after intravitreal bevacizumab injections in patients with and without diabetic kidney disease, evaluating whether these injections significantly affect renal function. Methodology: This quasi-experimental study was conducted in the Department of Ophthalmology, Bangabandhu Sheikh Mujib Medical University (BSMMU), from April 2019 to August 2021. Forty patients with diabetic retinopathy were selected, divided equally into DKD and non-DKD groups. Serum creatinine and eGFR were measured within 30 days before the injection and one month after the third dose of intravitreal bevacizumab. eGFR was calculated using the CKD-EPI equation, and statistical analysis was performed using SPSS. Results: The mean pre-injection eGFR was 69.35±25.91 ml/min/1.73m² in the DKD group and 96.7±30.59 ml/min/1.73m² in the non-DKD group. Post-injection, the mean eGFR was 73.3±33.87 ml/min/1.73m² in DKD patients and 93.6±29.7 ml/min/1.73m² in non-DKD patients. The mean differences in eGFR were not statistically significant between pre- and post-injection measurements in either group (p&gt;0.05). Conclusion: Intravitreal bevacizumab injections did not cause significant changes in eGFR in both DKD and non-DKD patients, suggesting that the treatment is unlikely to have a detrimental impact on renal function in the short term. Further studies are needed to assess the long-term effects of repeated injections.

First-year real-world experience of intravitreal brolucizumab injection for refractory neovascular age-related macular degeneration.

To investigate the first-year real-world anatomical and functional outcomes of intravitreal brolucizumab injection in eyes with refractory neovascular age-related macular degeneration (nAMD). Retrospective observational study. nAMD patients who showed poor response to previous anti-vascular endothelial growth factor (VEGF) agents were switched to brolucizumab. Functional and anatomical outcomes were evaluated at initial treatment of nAMD, after treatment with other anti-VEGF agents and after switching and treating with brolucizumab for 1 year. Safety profile was also evaluated after brolucizumab injection. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), subfoveal choroidal thickness (SFCT), and the presence of fluid in different compartments (intraretinal fluid [IRF], subretinal fluid [SRF], pigment epithelial detachment [PED]) were assessed at each time point. A total of 40 eyes of 40 patients were included in the study. BCVA remained unchanged throughout treatment (p > 0.05). CFT did not change after treatment with other anti-VEGF agents (p = 0.588) but decreased after switching to brolucizumab (p < 0.001). SFCT decreased after treatment with other anti-VEGF agents (p = 0.025) but not after switching to brolucizumab (p = 0.236). Presence of SRF (p = 0.001) and PED (p = 0.001) decreased significantly after switching to brolucizumab, despite their persistence with prior treatments using other anti-VEGF agents. However, IRF persisted even after switching to brolucizumab (p = 0.745). Intraocular inflammation (IOI)-related adverse events were reported in 3 eyes (7.14%). Analysis of first-year real-world outcomes after switching to brolucizumab in nAMD patients refractory to other anti-VEGF agents showed improved anatomic outcomes, limited functional improvement and low incidence of IOI-related adverse events.

Bilateral Anti VEGF on Same Day-Investigation on Safety in Retinopathy of Prematurity (BASISROP)- A Multicenter retrospective study

PurposeTo report incidence of procedure related complications in preterm infants with ROP treated with intravitreal anti vascular endothelial growth factors (anti VEGF) injection in both eyes on same day DesignRetrospective, multicenter case series SubjectsPreterm infants with ROP treated with anti VEGF bilaterally on same day MethodsIntervention: All included infants underwent intravitreal anti VEGF injection in both eyes under aseptic precautions in ophthalmic operation theatre (OT) or neonatal intensive care unit (NICU). Postoperative examination was performed to look for procedure related complications Main Outcome MeasuresIncidence of procedure related complication (Presumed endophthalmitis, intraocular inflammation, lens injury, vitreous hemorrhage, retinal tear) in the study cohort. To study association of indication, type of anti VEGF, type of needle used, setting of procedure, site of injection (distance from limbus) and experience of the treating ophthalmologist with the complications. Results9984 eyes of 4992 infants were analysed. The procedure was most commonly performed in ophthalmic OT (8258, 82.7%) using 29G (4514, 45.2%) needle between 1-1.5 mm (9984, 100%) from limbus. Aggressive retinopathy of prematurity was the most common indication for anti VEGF use (4866, 48.7%) while Bevacizumab was the most commonly used anti VEGF agent (8642, 86.6%). Overall, 26 eyes (0.3%) had procedure related complications. Lens injury (15, 0.15%) and presumed endophthalmitis (7, 0.07%) were most common complications. One eye had culture proven endophthalmitis with Pseudomonas aeruginosa. No case of bilateral endophthalmitis was noted. Endophthalmitis was not associated with setting of procedure or type of anti VEGF used, while risk of lens injury was seven times higher when performed in NICU and 30 times higher when performed by an ophthalmologist with < 1year of experience in injecting anti VEGF in preterm infants. ConclusionsThe incidence of presumed endophthalmitis after bilateral same day anti VEGF in infants with ROP is 0.07%. These infants can be treated in both eyes on same day with the anti VEGFs and needles (29-32G) evaluated in this study, with emphasis on the direction of needle parallel to visual axis. Extra precaution is advocated if the procedure is planned in NICU or by an ophthalmologist with limited experience.

Diabetic Retinopathy Leading to Blindness- A Review.

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes that damages the retina, leading to blindness. People with type 1 diabetes are at greater risk of developing DR than people with type 2 diabetes. Diabetic retinopathy may be divided into two primary categories: Proliferative diabetic retinopathy (PDR) and non-proliferative diabetic retinopathy (NPDR). There are multiple risk factors for the onset and progression of diabetic retinopathy, such as hypertension, obesity, smoking, duration of diabetes, and genetics. Numerous investigations have evaluated the levels of a wide range of inflammatory chemokines within DR patients' serum, vitreous, and aqueous fluids. In diabetic retinopathy, the vitreous fluid exhibited rises in angiogenic factors like platelet-derived growth factor (PDGF) or vascular endothelial growth factor (VEGF) or declines in antiangiogenic factors like pigment epithelium-derived factor (PEDF). For prevention of diabetic retinopathy, more physical activity as well as less sedentary behavior were linked to a reduced likelihood of DR. Supplementing with nutraceuticals containing vitamins (B1, B2, B6, B12, C, D, E, and l-methyl folate) and mineral (zinc) can help decrease or avoid an outbreak of DR. Only laser photocoagulation and Anti-vascular endothelial growth factor (Anti-VEGF) injections are advised as favorable therapies in severe retinopathy. When it comes to treating DR's VEGF levels, inflammation, oxidative stress, apoptosis, and angiogenesis, Traditional Chinese medicine (TCM) has an excellent future.

Morphometrics of polypoidal choroidal vasculopathy lesions and choroidal vascular associated with treatment response using swept-source optical coherence tomography angiography

PurposeTo evaluate quantitative metrics of neovascularization lesions and choroidal vascular using swept-source optical coherence tomography angiography (SS-OCTA) in polypoidal choroidal vasculopathy (PCV) eyes, and investigate the relationship between imaging biomarkers and treatment outcomes of intravitreal anti-vascular endothelial growth factor (VEGF). MethodsWe retrospectively recruited 56 PCV patients. Choroidal features included subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI). Quantitative metrics of neovascularization lesions included total vessel length (TVL), average vessel length (AVL), junction density (JD), total number of endpoints (TNE), and mean lacunarity (ML). We performed multivariate logistic and linear regression models to determine the prognostic factors for functional and morphological outcomes. ResultsBy comparison, functional good-responders had poorer best corrected visual acuity, higher TNE, and lower ML at baseline. Morphological good-responders had higher central retinal thickness, higher TNE, lower TVL and AVL, lower ML, lower SFCT and CVI. High-shrinkage of vessel area subgroup had higher JD and TNE, lower TVL and AVL, lower ML, lower SFCT and CVI. Multivariate analysis showed good morphological response was correlated with lower SFCT (P < 0.01). High-shrinkage subgroup was correlated with lower AVL (P = 0.017) and higher TNE (P < 0.01). ConclusionQuantitative metrics of neovascularization lesions and choroidal characteristics using SS-OCTA had the potential to be imaging biomarkers for predicting the response to anti-VEGF treatment. PCV lesions with higher TNE and lower AVL tended to appear higher shrinkage of vessel area, and lower SFCT was correlated with good morphological response.

Term infant brain MRI after ROP treatment by anti-VEGF injection versus laser therapy.

Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents is used to treat posterior type 1 retinopathy of prematurity (ROP). Recent reports indicate that anti-VEGF therapy may be associated with white matter brain injury, according to animal studies, and neurodevelopmental impairments in children born preterm. We investigated whether type 1 ROP treated with bevacizumab is associated with structural brain injury on infant term magnetic resonance images (MRIs) in very low birth weight infants compared with those treated with laser ablation. We retrospectively reviewed the medical records of very low birth weight infants from 2006 to 2021 with type 1 ROP who had been treated with laser or anti-VEGF therapy. Intravitreal bevacizumab injection was used for type 1 ROP in zone 1 or very posterior zone 2 or when laser treatment was not feasible. A pediatric neuroradiologist reviewed brain MRIs at term equivalent age (36-46 weeks' postmenstrual age) and classified infants for severity (no/mild vs moderate/severe) of overall brain and white matter injury using the validated Kidokoro scoring system. Fifty-two infants met inclusion criteria: 35 (67%) treated with laser and 17 (33%) with bevacizumab. Moderate-to-severe brain injury scores were not statistically different between bevacizumab and laser treatment groups in either continuous or binary adjusted analyses, for either the overall score or the white matter subscore. Severity of structural injury on term brain MRI (total and white matter) did not differ between infants with type 1 ROP treated with anti-VEGF agent (bevacizumab) and those treated with laser ablation.

What are the effects of anti-vascular endothelial growth factors (anti-VEGF) on people undergoing vitrectomy for complications of proliferative diabetic retinopathy?

What are the effects of anti-vascular endothelial growth factors (anti-VEGF) on people undergoing vitrectomy for complications of proliferative diabetic retinopathy?

Association between renal function and the Treatment of Diabetic Macular Edema in Long-Term Cohort Study

To determine the correlation between the severity of chronic kidney disease (CKD) and treatment of diabetic macular edema (DME). The retrospective 2-year cohort study included eyes with DME confirmed using spectral-domain optical coherence tomography in Taipei Veterans General Hospital, Taiwan, between 2010 and 2020. All the eyes were treated with an intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) during regular follow-up around 2 years. They were categorized into 3 different groups: an estimated glomerular filtration rate ≥ 60 (mL/min per 1.73 m2) (group A), < 60 (group B), and patients undergoing hemodialysis (group C). The main outcome measures were (1) visual improvement, (2) structural improvement, and (3) the injection frequency of anti-VEGF in the different groups. In this study, 167 eyes from 120 patients were enrolled. Compared with groups B and C, the eyes in group A experienced the only significant visual improvement at month 3, month 6, and month 12 (P = 0.0001, 0.0002, 0.0013, respectively). The presence of subretinal fluid and intraretinal cysts was significantly decreased in groups A and B. In the treatment frequency analysis, the number of injections was the highest in group A and lowest in group C during the study period (P = 0.04). The severity of CKD had an impact on the DME treatment. The less severe CKD was, the greater the visual improvement that could be achieved. In addition, relatively poor renal function required a lower anti-VEGF injection frequency. The active prevention of the progression of CKD may play a key role in DME treatment.

Factors influencing the outcomes of trabeculectomy, conventional canaloplasty, and mitomycin C augmented canaloplasty.

To compare the efficacy, safety, and factors influencing the outcomes of trabeculectomy (TE), conventional canaloplasty (cCP), and mitomycin C augmented canaloplasty (mCP) in glaucoma patients. Intraocular pressure (IOP), the number of IOP-lowering eye drops, and surgery-related complications were evaluated at baseline and through 18months postoperatively. Correlations between patients' demographic data, ophthalmic and non-ophthalmic conditions, outcomes and complications were evaluated. 171 patients were included. IOP and IOP-lowering eye drops were significantly (p < 0.001) reduced 18months after TE, cCP, and mCP. At the 18-month follow-up, IOP and IOP-lowering eye drops were significantly lower following TE than cCP (p < 0.001, p = 0.010, respectively) and mCP (p = 0.010, p = 0.014). At the 18-month follow-up, complete success rates were significantly higher after TE compared to cCP and mCP for IOP ≤ 21, 18, and 16mmHg (p < 0.001). Qualified success rates for IOP ≤ 16mmHg were higher following TE than cCP and mCP (p = 0.023). In the TE group, clinical hypotony at any postoperative follow-up was positively correlated with previous intravitreal anti-vascular endothelial growth factor (VEGF)-therapy (p < 0.001), leukaemia (p = 0.002), and a spherical equivalent < -3 dioptres (p < 0.001). There were no significant correlations in the cCP and mCP groups. TE, cCP, and mCP led to a significant reduction in IOP and IOP-lowering eye drops during 18months of follow-up. At 18months of follow-up, IOP and IOP-lowering eye drops were significantly lower following TE compared to cCP and mCP. Anti-VEGF-therapy, cystostatic therapy in leukaemia, and a spherical equivalent < -3 dioptres were significantly correlated with postoperative hypotony, macular folds, and choroidal detachment in the TE group. What is known • Trabeculectomy (TE) is considered the gold standard in the surgical management of glaucoma. However, TE involves extensive postoperative management and might be associated with severe surgery-related complications. What is new • In this study, intraocular pressure (IOP) and IOP-lowering eye drops were significantly lower following TE compared to conventional canaloplasty (cCP) and mitomycin C augmented canaloplasty (mCP) at a follow-up of 18months. • In patients undergoing TE, anti-VEGF-therapy, cystostatic therapy in leukaemia, and a spherical equivalent < -3 dioptres were significantly correlated with postoperative hypotony, macular folds, and choroidal detachment.

Dry and neovascular "wet" age-related macular degeneration: Upcoming therapies.

The age-related macular degeneration (AMD) field is witnessing promising advancements in therapeutic options. Breakthrough drugs such as pegcetacoplan and avacincaptad have been FDA-approved for dry AMD, marking a significant development as there were no treatment options until August 2023. While several antivascular endothelial growth factor (VEGF) inhibitors have been approved for wet AMD, challenges persist with the need for frequent dosing. New treatments such as gene therapy, cell therapy, WNT pathway agonists, complement inhibitors, and anti-VEGF combination drugs are under development to address these issues. These developments are exciting and hold promise for transforming the field of medicine, offering hope for improved outcomes and enhanced patient care in managing AMD.