Anti-vascular Endothelial Growth Factor Treatment Research Articles

Cardiovascular and cerebrovascular adverse events associated with intravitreal anti-vascular endothelial growth factor monoclonal antibodies: a World Health Organization pharmacovigilance study

PurposeTo analyze cardiovascular and cerebrovascular adverse events (ADRs) after intravitreal anti-vascular endothelial growth factor (VEGF; aflibercept, bevacizumab, brolucizumab, and ranibizumab) treatment. SubjectsVigiBase, a World Health Organization (WHO) global safety report database DesignPharmacovigilance study MethodsThe individual-case-safety reports (ICSR) of cardiovascular and cerebrovascular ADRs after intravitreal anti-VEGF treatment were compared with those reported in the full database. From 2004 to 2023, 23,129 ADRs after intravitreal anti-VEGF therapy and 25,015,132 ADRs associated with any drug (full database). Main Outcome MeasuresThe reporting odds ratio (ROR) and information components (IC) were calculated, and the 95% lower credibility interval endpoint of the information component (IC025) was used for disproportionate Bayesian reporting. Inter-drug comparisons were performed using the ratio of odd ratio (rOR). ResultsCompared with the full database, anti-VEGFs were associated with an increased reporting of myocardial infarction (IC025 0.75; ROR: 1.78 [95% CI 1.70–1.86]), angina pectoris (IC025 0.53; ROR: 1.61 [95% CI 1.47–1.77]), arrythemias including atrial fibrillation, atrial flutter, ventricular fibrillation, supraventricular tachycardia (all IC025 >0, ROR>1), hypertension (IC025 2.22; ROR: 4.91 [95% CI 4.82–5.01]), and hypertensive crisis (IC025 1.97; ROR: 4.49 [95% CI 4.07–4.97]). Moreover, anti-VEGFs were associated with a higher reporting of cerebrovascular ADRs such as cerebral infarction (IC025 4.34; ROR: 23.19 [95% CI 22.10–24.34]), carotid artery stenosis (IC025 1.85; ROR: 5.24 [95% CI 3.98–6.89]), cerebral hemorrhage (IC025 2.29; ROR: 5.38 [95% CI 5.03–5.76]), and subarachnoid hemorrhage (IC025 1.98; ROR: 4.81 [95% CI 4.14–5.6]). Inter-drug comparison indicated that compared to ranibizumab, patients with aflibercept showed overall under-reporting of cardiovascular and cerebrovascular ADRs such as myocardial infarction (rOR 0.55 [95% CI 0.49–0.52]), atrial fibrillation (rOR 0.28 [95% CI 0.23–0.35]), cerebrovascular accident (rOR, 0.15 [95% CI 0.14–0.17]), and cerebral hemorrhage (rOR, 0.51 [95% CI 0.40–0.65]). ConclusionsIn this pharmacovigilance case-noncase study, significantly increased reporting of cardiovascular and cerebrovascular ADRs were identified after intravitreal anti-VEGF treatment. While ranibizumab may exhibit superior systemic safety regarding its biological characteristics, it is crucial not to overlook the occurrence of cardiovascular and cerebrovascular ADRs considering its higher reporting rate than bevacizumab or aflibercept.

An Overview of Best Disease

The German ophthalmologist Friedrich Best named Best vitelliform macular dystrophy (BVD), sometimes referred to as Best disease, in 1905 when he discovered a family with a history of early-onset macular degeneration. A Swedish study assessed the frequency of BVMD to be 2 in 10,000, whereas a Danish examination found 1.5 in 100,000 cases. If a parent with the condition has a kid with an unaffected spouse, there is a 50% chance that the child will inherit the condition from the parent. The syndrome is caused by a mutation in the VMD2 or BEST1 gene found at chromosome 11q12-q13. It is yet unclear how bestrophinopathies pathophysiologically operate. An ionic imbalance in the RPE milieu, which BEST1 gene mutations can bring on, can lead to impaired RPE functions. The best sickness is in five phases. There is currently no recognized treatment for the best sickness. One treatment option for CNV is VEFG injections, either used alone or in conjunction with photodynamic therapy (PDT). Anti-vascular endothelial growth factor (Anti- VEGF) treatments can prevent or reduce the creation of new blood vessels. This can postpone the onset of blindness and slow down the rate at which they leak.

Prediction of Long-Term Treatment Outcomes for Diabetic Macular Edema Using a Generative Adversarial Network.

The purpose of this study was to analyze optical coherence tomography (OCT) images of generative adversarial networks (GANs) for the prediction of diabetic macular edema after long-term treatment. Diabetic macular edema (DME) eyes (n = 327) underwent anti-vascular endothelial growth factor (VEGF) treatments every 4 weeks for 52 weeks from a randomized controlled trial (CRTH258B2305, KINGFISHER) were included. OCT B-scan images through the foveal center at weeks 0, 4, 12, and 52, fundus photography, and retinal thickness (RT) maps were collected. GAN models were trained to generate probable OCT images after treatment. Input for each model were comprised of either the baseline B-scan alone or combined with additional OCT, thickness map, or fundus images. Generated OCT B-scan images were compared with real week 52 images. For 30 test images, 28, 29, 15, and 30 gradable OCT images were generated by CycleGAN, UNIT, Pix2PixHD, and RegGAN, respectively. In comparison with the real week 52, these GAN models showed positive predictive value (PPV), sensitivity, specificity, and kappa for residual fluid ranging from 0.500 to 0.889, 0.455 to 1.000, 0.357 to 0.857, and 0.537 to 0.929, respectively. For hard exudate (HE), they were ranging from 0.500 to 1.000, 0.545 to 0.900, 0.600 to 1.000, and 0.642 to 0.894, respectively. Models trained with week 4 and 12 B-scans as additional inputs to the baseline B-scan showed improved performance. GAN models could predict residual fluid and HE after long-term anti-VEGF treatment of DME. The implementation of this tool may help identify potential nonresponders after long-term treatment, thereby facilitating management planning for these eyes.

Approved AI-based fluid monitoring to identify morphological and functional treatment outcomes in neovascular age-related macular degeneration in real-world routine

AimTo predict antivascular endothelial growth factor (VEGF) treatment requirements, visual acuity and morphological outcomes in neovascular age-related macular degeneration (nAMD) using fluid quantification by artificial intelligence (AI) in a real-world...

Quantifying Changes on OCT in Eyes Receiving Treatment for Neovascular Age-Related Macular Degeneration

PurposeApplication of artificial intelligence (AI) to macular optical coherence tomography (OCT) scans to segment and quantify volumetric change of anatomical and pathological features during intravitreal treatment for neovascular age-related macular degeneration (AMD). DesignRetrospective analysis of OCT images from the Moorfields Eye Hospital AMD Database. Participants2115 eyes from 1883 patients that started anti-vascular endothelial growth factor (anti-VEGF) treatment between 1st June 2012 and 30th June 2017. MethodsThe Moorfields Eye Hospital neovascular AMD database was queried for first and second eyes that received anti-VEGF treatment and had an OCT scan at baseline and at 12 months. Follow-up scans were input into the AI system to derive volumetric outputs for the following variables: intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), subretinal hyperreflective material (SHRM), hyperreflective foci (HRF), neurosensory retina (NSR) and retinal pigment epithelium (RPE). Volumes were studied at different time points and comparisons made with respect to baseline volume groups. Cross-sectional comparisons between time points were conducted using Mann-Whitney U test. ResultsMean volumes of analysed features decreased significantly from baseline to both four and 12 months, in both first and second-treated eyes. Pathological features that reflect exudation, including pure fluid components (IRF and SRF) and those with a mixture of fluid and fibrovascular tissue (PED and SHRM), displayed similar response to treatment over 12 months. Mean PED and SHRM volumes showed less pronounced but also substantial decreases over the first two months, reaching a plateau post loading phase, and minimal change to 12 months. Both NSR and RPE volumes showed gradual reductions over time, and not as substantial as exudative features. Conclusion:We report the results of a quantitative analysis of change in retinal segmented features over time, enabled by an AI segmentation system. Cross-sectional analysis at multiple time points demonstrated significant associations between baseline OCT-derived segmented features and the volume of biomarkers at follow-up. Demonstrating how certain OCT biomarkers progress with treatment and the impact of pre-treatment retinal morphology on different structural volumes may provide novel insights into disease mechanisms and aid personalization of care. Data will be made public for future studies.

Progression of macular retinoschisis following intravitreal aflibercept injection for myopic macular neovascularization—a case report and review of literature

BackgroundMacular retinoschisis (MRS) and myopic macular neovascularization (mMNV) are both potentially blinding complications of high myopia. In this case report, we highlight the progression of MRS after intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for mMNV, as well as an extensive review of the literature on this topic.Case descriptionA 49-year-old woman presented with two weeks of recent onset blurring and metamorphopsia in her right eye. She had high myopia in both eyes (right eye − 20/60 with − 16D, left eye − 20/20 with − 13D). Slit-lamp ophthalmoscopy found a normal anterior segment in both eyes. On fundus examination, features of pathological myopia with posterior staphyloma and peripapillary atrophy were observed in both eyes. An active mMNV, as well as intraretinal fluid, minimal perifoveal inner and outer MRS, and focal posterior vitreous traction along the inferotemporal retinal arcade, were detected on optical coherence tomography (OCT) of the right eye. The patient received an intravitreal injection of Aflibercept (2 mg/0.05 ml).ResultsOCT scans at two- and four-month follow-up visits revealed regressed mMNV with a taut epiretinal membrane, progressive worsening of outer MRS, and the development of multiple perifoveal retinal detachment inferior to the fovea. Pars plana vitrectomy surgery was performed for the progressive MRS with good anatomical (resolved MRS) and functional outcome (maintained visual acuity at 20/60) at the last one-month post-surgery visit.ConclusionIntravitreal anti-VEGF injections for mMNV can cause vitreoretinal interface changes, exacerbating MRS and causing visual deterioration. Vitrectomy for MRS could be one of several treatment options.

Association of the Complement Factor H Y402H Polymorphism and Response to Anti-Vascular Endothelial Growth Factor Treatment in Age-Related Macular Degeneration: An Updated Meta-Analysis.

Anti-vascular endothelial growth factor (anti-VEGF) agents have a variable effect on patients with age-related macular degeneration (AMD) that has been attributed to several causes, including genetic factors. We evaluated the effects of Complement Factor H (CFH) rs1061170/Y402H polymorphism on the response to anti-VEGF therapy among AMD patients. PubMed, Scopus, EMBASE, Web of Science, and Google Scholar were used for a literature search. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated to assess the effects of CFH Y402H polymorphism on the response to anti-VEGF therapy in AMD. I2 was used to present the amount of heterogeneity. We used STATA version 14.0 software. Twenty-five papers reporting data for 4,681 patients were included in this study. Better response to anti-VEGF therapy was seen in T over C (OR = 1.25, 95% CI = 1.04-1.50), TT over CC (OR = 1.60, 95% CI = 1.06-2.4), and TT + TC over CC (OR = 1.68, 95% CI = 1.23-2.28) genotypes. There was no significant difference in the three other genetic models (TT vs. TC, TT vs. TC + CC, TC vs. TT + CC). In Asians, no significant difference was observed in all six genetic models. Ranibizumab and bevacizumab had similar efficacy; however, conbercept was more effective in homozygous genotypes. The literature indicated that TT and TC genotypes and T allele were associated with a better functional response, while the CC genotype and C alleles had a better anatomical response. The combination of risk alleles in ARMS2 A69S (rs10490924), VEGF-A (rs699947), and VEGF-A (rs833069) with Y420H is a predictor of non-respondents. In patients with AMD, the CFH Y402H is a predictor of the response to anti-VEGF agents and should be considered in the treatment plan.

Genetics in neovascular age-related macular degeneration susceptibility and treatment response to anti-VEGF intravitreal injection: A case series study.

To identify genotypes associated with neovascular age-related macular degeneration (nAMD) and investigate the associations between genotype variations and anti-vascular endothelial growth factor (VEGF) treatment response. This observational, retrospective, case series study enrolled patients diagnosed with nAMD who received anti-VEGF treatment in National Taiwan University Hospital with at least one-year follow-up between 2012 and 2020. A genome-wide association study (GWAS) was conducted on enrolled patients and controls. Correlations between the genotypes identified from GWAS and the treatment response of functional/anatomical biomarkers, including visual acuity (VA), presence of intraretinal or subretinal fluid (SRF), serous or fibrovascular pigmented epithelium detachment (PED), and disruption of the ellipsoid zone (EZ), were analysed. In total, 182 patients with nAMD and 1748 controls were enrolled. GWAS revealed 16 single nucleotide polymorphisms (SNPs) as risk loci for nAMD, including seven loci in CFH and ARMS2/HTRA1 and nine novel loci, including rs117517872 and rs79835234(COPB2-DT), rs7525578(RAP1A), rs2123738(LOC105376755), rs1374879(CNTN3), rs3812692(SAR1A), rs117501587(PRKCA), rs9965945(CNDP1), and rs189769231(MATK). Our study revealed rs800292(CFH), rs11200638(HTRA1), and rs2123738(LOC105376755) correlated with poor treatment response in VA (P = 0.005), SRF (P = 0.044), and fibrovascular PED (P = 0.007), respectively. Rs9965945(CNDP1) was correlated with poor response in disruption of EZ (P = 0.046) and serous PED (P = 0.049). Among the 16 SNPs found in the GWAS, four loci-CFH, ARMS2/HTRA1, and two novel loci-were correlated with the susceptibility of nAMD and anatomical/functional responses after anti-VEGF treatment.

Intravitreal Anti-Vascular Endothelial Growth Factor Treatment in Patients with Neovascular Age-Related Macular Degeneration and Poor Visual Acuity

Purpose: To investigate the significance of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with neovascular age-related macular degeneration (nAMD) and poor visual acuity (VA). Methods: Retrospective study of patients with nAMD with baseline best corrected VA of ≤ 20/200. Patients were divided into regular treatment (RT) and scarce treatment (ST) groups according to whether they underwent consecutive intravitreal anti-VEGF treatments at intervals of ≤ 4 months or not. Results: A total of 131 eyes were included: 87 and 44 eyes in the RT and ST groups, respectively. RT group showed significantly improved preservation of lesion size at both years 1 and 2, with significantly fewer incidences of new subretinal hemorrhage (SRH). Improvements in VA, reduction in central subfield macular thickness (CST), and maximal height of choroidal neovascularization were significantly favorable in RT group at year 1, and CST was significantly decreased at year 2. Survival analysis revealed that RT group had significantly greater preservation of VA and lesion size than that in ST group. Conclusion: Maintaining intravitreal anti-VEGF treatment for patients with nAMD and poor vision showed significant advantages in VA and lesion size stability and reduced the incidence of new SRH, which suggests preservation of paracentral vision.

Patient Experience Survey of Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema.

Understanding patient perspectives of treatment may improve adherence and outcomes. This study explored real-world patient experiences with anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD). This multinational, non-interventional, quantitative, cross-sectional, observational survey assessed treatment barriers/burden, patient-reported visual functioning, and treatment satisfaction in DME and nAMD patients in the USA, the UK, Canada, France, Italy, and Spain. Treatment patterns and visual outcomes were extracted from medical charts. Regression models evaluated relationships between adherence, total missed visits, number of anti-VEGF injections, and clinical and patient-reported outcomes for visual functioning. Association between treatment satisfaction and aspects of burden were assessed. The survey was completed by 183 DME and 391 nAMD patients. Patients had moderately high vision-related functioning (25-item National Eye Institute Visual Functioning Questionnaire score: mean = 74.8) and were satisfied with their current treatment (mean total score: Macular Disease Treatment Satisfaction Questionnaire = 59.2; Retinopathy Treatment Satisfaction Questionnaire = 61.3). Treatment satisfaction scores were worse with higher time-related impacts of treatment (nAMD/DME), higher impacts on finances and daily life (nAMD), negative impacts on employment and lower expectations for treatment effectiveness (DME). Most patients reported ≥1 barrier (66.1% DME, 49.2% nAMD patients) related to treatment (35.0%), clinic (32.6%), and COVID-19 (21.1%). Moreover, 44.9% of patients reported some impairment in activities of daily living. Work absenteeism was observed among >60% of working patients. Nearly one-quarter (24.2%) of patients needed ≥1 day to recover from intravitreal injections; most reported ≥30 min of travel time (73.7%) and clinic wait time (54.2%). In unadjusted univariable analyses, treatment adherence (vs. nonadherence) was related to higher most recent visual acuity (β = 8.98 letters; CI, 1.34-16.62) and lower odds of visual acuity below driving vision (≤69 letters) (OR = 0.50; CI, 0.25-1.00). More durable treatments with reduced frequency of injections/visits may reduce treatment burden and improve patient satisfaction, which may enhance adherence and visual outcomes.

4D label-free proteomics analysis of oxygen-induced retinopathy with or without anti-VEGF treatment

Oxygen-induced retinopathy (OIR) animal model is widely used for retinopathy of prematurity (ROP) researches. The purpose of this study was to identify proteins and related pathways of OIR with or without anti-vascular endothelial growth factor (VEGF) treatment, for use as biomarkers in diagnosing and treating ROP. Nine samples were subjected to proteomic analysis. Retina specimens were collected from 3 OIR mice, 3 OIR mice with anti-VEGF treatment and 3 normal mice (control group). Liquid chromatography-tandem mass spectrometry analysis was performed using the 4D label-free technique. Statistically significant differentially expressed proteins, gene ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway representations, InterPro (IPR) and protein interactions were analyzed. In total, 4585 unique proteins were identified as differentially expressed proteins (DEPs). Enrichment analysis of the GO and KEGG indicated functional clusters related to peptide biosynthetic and metabolic process, cellular macromolecule biosynthetic process and nucleic acid binding in OIR group. For anti-VEGF treatment group, DEPs were clustered in DNA replication, PI3K/Akt signaling pathway and Jak/STAT signaling pathway. Proteomic profiling is useful for the exploration of molecular mechanisms of OIR and mechanisms of anti-VEGF treatment. These findings may be useful for identification of novel biomarkers for ROP pathogenesis and treatment.

Machine learning and optical coherence tomography-derived radiomics analysis to predict persistent diabetic macular edema in patients undergoing anti-VEGF intravitreal therapy

BackgroundDiabetic macular edema (DME) is a leading cause of vision loss in patients with diabetes. This study aimed to develop and evaluate an OCT-omics prediction model for assessing anti-vascular endothelial growth factor (VEGF) treatment response in patients with DME.MethodsA retrospective analysis of 113 eyes from 82 patients with DME was conducted. Comprehensive feature engineering was applied to clinical and optical coherence tomography (OCT) data. Logistic regression, support vector machine (SVM), and backpropagation neural network (BPNN) classifiers were trained using a training set of 79 eyes, and evaluated on a test set of 34 eyes. Clinical implications of the OCT-omics prediction model were assessed by decision curve analysis. Performance metrics (sensitivity, specificity, F1 score, and AUC) were calculated.ResultsThe logistic, SVM, and BPNN classifiers demonstrated robust discriminative abilities in both the training and test sets. In the training set, the logistic classifier achieved a sensitivity of 0.904, specificity of 0.741, F1 score of 0.887, and AUC of 0.910. The SVM classifier showed a sensitivity of 0.923, specificity of 0.667, F1 score of 0.881, and AUC of 0.897. The BPNN classifier exhibited a sensitivity of 0.962, specificity of 0.926, F1 score of 0.962, and AUC of 0.982. Similar discriminative capabilities were maintained in the test set. The OCT-omics scores were significantly higher in the non-persistent DME group than in the persistent DME group (p < 0.001). OCT-omics scores were also positively correlated with the rate of decline in central subfield thickness after treatment (Pearson’s R = 0.44, p < 0.001).ConclusionThe developed OCT-omics model accurately assesses anti-VEGF treatment response in DME patients. The model’s robust performance and clinical implications highlight its utility as a non-invasive tool for personalized treatment prediction and retinal pathology assessment.

Anti-VEGF Treatment for Secondary Neovascularization in Pseudoxanthoma Elasticum - Age of Onset, Treatment Frequency, and Visual Outcome

PurposeTo assess the onset, treatment frequency, and visual outcome of anti-vascular endothelial growth factor (anti-VEGF) treatment due to secondary choroidal neovascularization (CNV) in patients with pseudoxanthoma elasticum (PXE). DesignRetrospective cohort study MethodsOne-hundred six eyes of 53 patients with PXE were analyzed. The assessment of CNV activity relied on hemorrhage visible on funduscopy and intra- / subretinal fluid on optical coherence tomography (OCT), individually defining a shortening or extension of treatment interval. Best-corrected visual acuity (BCVA) at baseline, age at anti-VEGF therapy initiation, and BCVA-drop events at exudation onset (worsening of BCVA of 2 or more lines) were documented. Further, we assessed the number of injections during the first year and the total number of injections, the time to treatment initiation of the fellow eye, and BCVA over time. ResultsDuring a median observation period of 77 months (IQR 49; 126) patients received a median number of 28.0 anti VEGF-injections (IQR 9.8; 43.5). Eight patients received no injection (median age at baseline 38.1 years), 11 patients underwent anti-VEGF treatment in one eye (median age 47.2 years) and 34 patients in both eyes (median age 51.8 years). The median age at the first anti-VEGF treatment was 52.80 years (IQR 47.2 – 57.6). Applying Cox regression models, the median 'survival' time of fellow eye until treatment initiation was 16.8 months. In the group of bilateral treated patients, the median time difference was 9.6 months (IQR 2.1 – 32.4, range 0 – 122) The median number of injections was 5.5 per eye in the first year of treatment (IQR 3 – 7) and was associated with the total number of injections in the observation period (2.33, CI 1.22 – 3.44, p<0.001). A better BCVA at the last follow-up visit was associated with a better baseline BCVA (p<0.001, R2=0.318) and with the absence of a BCVA drop at the onset of exudation (p=0.035, R2=0.339). ConclusionsThe results of this study indicate that anti-VEGF treatment is required for most PXE patients at a relatively young age. Once treatment in one eye is initiated, the time to fellow eye treatment is relatively short. A BCVA drop before treatment initiation is a risk factor for worse visual outcomes, suggesting that treatment is prudent before exudation affects the central retina. Given the young age of onset and intensive treatment needs, patients with PXE might particularly benefit from longer-acting anti-VEGF therapeutics.

Exploring the Impact of Saccharin on Neovascular Age-Related Macular Degeneration: A Comprehensive Study in Patients and Mice.

We aimed to determine the impact of artificial sweeteners (AS), especially saccharin, on the progression and treatment efficacy of patients with neovascular age-related macular degeneration (nAMD) under anti-vascular endothelial growth factor (anti-VEGF-A) treatment. In a cross-sectional study involving 46 patients with nAMD undergoing intravitreal anti-VEGF therapy, 6 AS metabolites were detected in peripheral blood using liquid chromatography - tandem mass spectrometry (LC-MS/MS). Disease features were statistically tested against these metabolite levels. Additionally, a murine choroidal neovascularization (CNV) model, induced by laser, was used to evaluate the effects of orally administered saccharin, assessing both imaging outcomes and gene expression patterns. Polymerase chain reaction (PCR) methods were used to evaluate functional expression of sweet taste receptors in a retinal pigment epithelium (RPE) cell line. Saccharin levels in blood were significantly higher in patients with well-controlled CNV activity (P = 0.004) and those without subretinal hyper-reflective material (P = 0.015). In the murine model, saccharin-treated mice exhibited fewer leaking laser scars, lesser occurrence of bleeding, smaller fibrotic areas (P < 0.05), and a 40% decrease in mononuclear phagocyte accumulation (P = 0.06). Gene analysis indicated downregulation of inflammatory and VEGFR-1 response genes in the treated animals. Human RPE cells expressed taste receptor type 1 member 3 (TAS1R3) mRNA and reacted to saccharin stimulation with changes in mRNA expression. Saccharin appears to play a protective role in patients with nAMD undergoing intravitreal anti-VEGF treatment, aiding in better pathological lesion control and scar reduction. The murine study supports this observation, proposing saccharin's potential in mitigating pathological VEGFR-1-induced immune responses potentially via the RPE sensing saccharin in the blood stream.

Pro re nata anti-VEGF treatment in pachychoroid neovasculopathy compared with age-related macular degeneration based on optical coherence tomography.

To compare anti-vascular endothelial growth factor (anti-VEGF) treatment in pachychoroid neovasculopathy (PNV) and age related macular degeneration (AMD). Cases having pro re nata (PRN) anti-VEGF treatment for choroidal neovascularization were reviewed and grouped as PNV and AMD. Groups were compared according to central foveal thickness (CFT), best corrected visual acuity (BCVA), and total injection over 12months. The correlation of beginning choroidal thickness, CFT, and BCVA with final BCVA was analyzed. Forty-seven PNV and 65 AMD cases were reviewed. Both the PNV group (p = 0.0001) and the AMD group (p = 0.003) had a significant improvement in BCVA and a significant decrease in CFT (p = 0.0001). However, BCVA was better at the 3-, 6-, and 12-month follow-up in PNV (p = 0.003, 0.002, 0.02). No significant CFT difference was observed between groups. The total number of injections was 5.7 ± 1.7 for PNV and 5.2 ± 1.5 for AMD (p = 0.09). Beginning BCVA was positively correlated with final BCVA in both groups. The PRN treatment regimen was effective for PNV and AMD in terms of visual and anatomical outcomes. Visual response was better in PNV with PRN treatment with the same number of injections.

Analysis aqueous humor lipid profile of neovascular glaucoma secondary to diabetic retinopathy and lipidomic alteration response to anti-VEGF treatment

The objective of this study was to examine the lipid spectrum of aqueous humor (AH) in patients with neovascular glaucoma (NVG) secondary to proliferative diabetic retinopathy and to investigate the lipid alteration response to anti-vascular endothelial growth factor (anti-VEGF) treatment. Lipidomic analysis using ultra-high performance liquid chromatography–tandem mass spectrometry was conducted to compare the lipid profiles of the AH in NVG patients with those of a control group. Lipid changes in the AH of NVG patients before and after intravitreal conbercept injections were also evaluated. The identification of lipids showing differential expression was accomplished through both multivariate and univariate analyses. This study included 13 NVG patients and 20 control subjects. Based on LipidSearch software, 639 lipid species across 33 lipid classes were detected in the participants' AH. The combination of univariate and multivariate statistical analyses yielded 53 differentially expressed lipids (VIP >1 and P < 0.05). In addition, 9 lipids were found to be differentially expressed before and after the intravitreal conbercept injections in the NVG patients. Significant alterations in the metabolic pathways of glycerophospholipid and glycerolipid exhibited notable changes. Our results highlighted the lipid changes in patients’ AH in relation to the progression of NVG, and indicated that the modified lipids could potentially be utilized as therapeutic targets for NVG.

Anti-Vascular Endothelial Growth Factor Treatment in Diabetic Macular Edema-Results from a Large Single Center Cohort with Bevacizumab As First-Line Therapy.

To explore visual acuity (VA) outcomes of anti-vascular endothelial growth factor (VEGF) intravitreal injections in treatment-naive eyes with diabetic macular edema (DME), with bevacizumab as first-line treatment. Retrospective single-center cohort study over a three-year follow-up. 1765 eyes from 1179 patients treated with intravitreal injections were evaluated. The cohort was divided according to the treatment given: (1) bevacizumab monotherapy, (2) eyes switched to 2nd line agent, and (3) eyes switched to a 3rd line agent. 644 eyes of 444 patients met inclusion criteria. Mean age at presentation was 64.0±11.1 years. Mean follow-up period was 24.6±12.4 months. 67.1% of eyes were treated with bevacizumab monotherapy, 25.45% switched to a 2nd line agent, and 7.45% were switched to a 3rd line agent. Mean number of injections decreased significantly during each treatment year in the total cohort and within each treatment group (P<0.001). Mean VA for the total cohort and within each treatment group improved significantly throughout follow-up (P<0.001). No significant difference in VA found between the groups (P=0.373). This real-world study demonstrates robust and consistent VA gains over long-term follow-up in eyes with DME treated with either bevacizumab monotherapy or switching to alternative anti-VEGF agents in cases of suboptimal response.

Macular Neovascularization Secondary to Subclinical Angioid Streaks in Age-Related Macular Degeneration: Treatment Response to Anti-VEGF at 2-Year Follow-up.

To characterize the response to antivascular endothelial growth factor (VEGF) treatment of macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) with subclinical angioid streaks (AS) during a 2-year follow-up. Retrospective, longitudinal, case-control, and multicentric study. Among a cohort of neovascular AMD population, we selected patients with subclinical AS and treatment-naïve MNV treated with anti-VEGF for a 2-year follow-up. An age- and sex-matched control group with treatment-naïve MNV secondary to AMD without subclinical AS was selected. Demographics and differences in treatment response (i.e., number of injections needed, anatomical and functional outcomes) between the two groups were analyzed. Among 102 eyes of 102 patients with neovascular AMD, 34 eyes of 34 patients (82 ± 6years old) were included in the subclinical AS group, whereas 68 eyes of 68 patients (81 ± 6years old, p = 0.342) in the control group. All eyes with subclinical AS presented RPD compared to 56% of eyes without subclinical AS (p < 0.001). During the 2-year follow-up, eyes with subclinical AS needed more injections (10.6 ± 3.2 vs 8.3 ± 3.1 injections for eyes with and without subclinical AS, respectively, p < 0.001). Visual acuity (VA) decreased during the treatment (from 0.53 ± 0.37 at the baseline to 0.69 ± 0.45 LogMAR at 2-year follow-up, p = 0.044) in eyes with subclinical AS; no VA changes were observed in the control group (p = 0.798). RPE atrophy at the end of the 2-year follow-up affected 74% of cases with subclinical AS and 29% of cases of the control group (p < 0.001). MNVs secondary to AMD with subclinical AS are characterized by worse functional and anatomical outcomes after 2-year anti-VEGF treatment compared to MNV secondary to AMD without subclinical AS, supporting the different pathophysiological mechanisms involved in this recently described AMD phenotype.

Nonsurgical closure of full thickness macular hole under topical therapy in two eyes with pathologic myopia.

Non-surgical closure of a full-thickness macular hole (FTMH) with eye drops has recently been reported, but there are few similar reports in cases with pathologic myopia. (Case 1) The right eye of a 75-year-old female with an axial length of 28.83 mm had undergone anti-vascular endothelial growth factor (VEGF) treatment for choroidal neovascularization presented with FTMH. Topical betamethasone, bromfenac, and blinzolamide treatments were started, and the FTMH was closed with visual improvement (20/32 to 20/20) after 5 weeks. (Case 2) In the right eye of a 55-year-old male with an axial length of 30.81 mm and lacquer cracks, subretinal hyperreflective material and FTMH developed. The above three drugs were started after anti-VEGF drug injection. Sixteen weeks later, the FTMH was closed with visual improvement (20/63 to 20/20). Nonoperative closure of FTMH has already been reported, but few in eyes with pathologic myopia. Our results suggest that nonoperative closure of FTMH associated with pathologic myopia under eye drops may be possible in some cases.

Thrombospondin-1, BIM and CFH polymorphisms and response to anti-VEGF treatment in neovascular age- related macular degeneration patients.

Age-related macular degeneration (AMD) is a vision threatening disease in older adults. Anti-VEGF treatment is effective for the majority of neovascular AMD (nAMD) patients, although approximately 30% of nAMD patients have an incomplete response for unknown reasons. Here we assessed the contribution of single nucleotide polymorphisms (SNPs) in key angioinflammatory regulatory genes in nAMD patients with an incomplete response compared to those responsive to anti-VEGF treatment. A total of 25 responsive and 30 nAMD patients with an incomplete response to anti-vascular endothelial growth factor (anti-VEGF) treatment were examined for known SNPs that impact the structure and function of thromobospondin-1 (TSP1), Bcl-2-interacting mediator of cell death (BIM) and complement factor H (CFH). Plasma levels of C-C motif chemokine ligand 2 (CCL2/MCP1), TSP1 and VEGF were assessed by ELISA. Patients responsive to anti-VEGF treatment showed a significant increase in the TSP1 rs2228262 AA allele and a trend for the BIM (rs724710) CT allele. Consistent with previous reports, 42% of the patients responsive to anti-VEGF expressed the CC allele for CFH rs1061170. Although the CFH TT allele had similarly low prevalence in both groups, the TC allele tended to be more prevalent in patients with an incomplete response. Patients with an incomplete response also had increased plasma CCL2/MCP1 levels, consistent with the role increased inflammation has in the pathogenesis of nAMD. Our studies point to new tools to assess the potential responsiveness of nAMD patients to anti-VEGF treatment and suggest the potential use of anti-CCL2 for treatment of nAMD patients with an incomplete response to anti-VEGF.