anti-VEGF Therapy In Patients Research Articles

Cardiovascular Outcomes with Intravitreal Anti-Vascular Endothelial Growth Factor Therapy in Patients with Diabetes: A Real-World Data Analysis.

Anti-vascular endothelial growth factor (anti-VEGF) therapy is commonly used intravitreally for diabetic proliferative retinopathy, but when used systemically for treating cancers, an excess of cardiovascular disease (CVD) events has been noted. The latter is of concern for people with diabetes, who are at higher risk of CVD. This study aims to explore the relationship between incident CVD and intravitreal anti-VEGF therapy in patients with diabetes, compared to other therapies, using a large real-world global federated dataset. Data were analysed using TriNetX, a global electronic medical real-world ecosystem. The study included adults with diabetes and excluded those with a history of CVD prior to the time window of data extraction. Patients were categorised into two cohorts: anti-VEGF therapy or control cohort (laser or steroid therapies). The cohorts were 1:1 propensity score-matched for age, sex, ethnicity, body mass index, systolic blood pressure, HbA1c, and cardiovascular medications. Outcomes analysed at 1, 6 and 12months were: (1) mortality; (2) acute myocardial infarction (MI); (3) cerebral infarction; and (4) heart failure. Relative risk analyses were performed using the built-in R statistical computing platform on TriNetX. In patients with diabetes (n = 2205; mean age 58.8 ± 15.8, Stddiff 0.05; 56% male), anti-VEGF therapy was associated with a numerical but non-statistically significant increased CVD risk over 1, 6, and 12months: Mortality over 1month (RR 1; 95%CI 0.42, 2.40), 6months (RR 1.46; 95%CI 0.72, 2.95) and 12months (RR 1.41; 95%CI 0.88, 2.27). There was no excess of acute MI over 1 (RR n/a: not applicable; 0/0: 0 events in the anti-VEGF group/0 events in the control group), 6 and 12months (RR n/a; 0/10 events); cerebral infarction over 1, 6months (RR n/a; 0/0 events), and 12months (RR n/a; 0/10); and heart failure over 1month (RR n/a; 0/0 events), 6months (RR 1; 95%CI 0.42, 2.40) and 12months (RR 1; 95%CI 0.42, 2.34). There was no statistically significant risk of cardiovascular-related events in the short or medium term in patients with diabetes who received intravitreal anti-VEGF therapy, despite a small increase in the number of CVD events. Our study supports the real-world safety of intravitreal anti-VEGF therapy in patients with diabetes free of baseline CVD.

ASSOCIATION BETWEEN RETINAL PIGMENT EPITHELIUM TEAR AND ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY: A Systematic Review and Meta-Analysis.

To identify the prevalence of retinal pigment epithelium tear (RPET) after anti-vascular endothelial growth factor (VEGF) therapy and determine the efficacy of continued anti-VEGF therapy in patients with RPET. All relevant clinical trials and observational studies in several online databases were screened. The main outcomes were the incidence of RPET after anti-VEGF therapy and changes in visual acuity for patients with RPET treated with continued anti-VEGF. The pooled incidence of RPET after anti-VEGF therapy from 24 studies with 17,354 patients was 1.9% (95% CI: 1.3-2.7). Most new RPET cases were concentrated in the first month at baseline or after the first injection during anti-VEGF therapy and gradually decreased by the subsequent month or injection. 13 studies with 157 patients reported that for patients who received anti-VEGF therapy after RPET, their pooled best-corrected visual acuity improved, but did not reach a significant level (standardized mean differences 0.34; 95% CI: -0.03 to 0.71). The incidence of RPET after anti-VEGF therapy is low. The intravitreal anti-VEGF injection may accelerate this process. For patients with RPET, maintenance of anti-VEGF therapy ensures visual acuity stability.

Modulation of Hypoxia-Inducible Factors and Vascular Endothelial Growth Factor Expressions by Superfood Camu-Camu (Myrciaria dubia) Treatment in ARPE-19 and Fetal Human RPE Cells.

Anti-vascular endothelial growth factor (anti-VEGF) therapy via intravitreal injection is an effective treatment for patients with abnormal ocular neovascularization, such as age-related macular degeneration (AMD) and diabetic macular edema (DME). However, prolonged and frequent anti-VEGF treatment is associated with a risk of local and systemic adverse events, including geographic atrophy, cerebrovascular disease, and death. Furthermore, some patients do not adequately respond to anti-VEGF therapy. Hypoxia-inducible factor (HIF) is a transcription factor that controls the expression of hypoxia-responsive genes involved in angiogenesis, inflammation, and metabolism. The HIF/VEGF pathway plays an important role in neovascularization, and the inhibition of HIF activation could be an effective biomolecular target for neovascular diseases. The demand for disease prevention or treatment using functional foods such as superfoods has increased in recent years. Few reports to date have focused on the antineovascular effects of superfoods in the retinal pigment epithelium (RPE). In light of the growing demand for functional foods, we aimed to find novel HIF inhibitors from superfoods worked in RPE cells, which could be an adjuvant for anti-VEGF therapy. Seven superfoods were examined to identify novel HIF inhibitor candidates using luciferase assay screening. We used the human RPE cell line ARPE-19 and fetal human RPE (fhRPE) to investigate the biomolecular actions of novel HIF inhibitors using quantitative PCR and western blotting. Under CoCl2-induced pseudohypoxic condition and 1% oxygen hypoxic incubation, camu-camu (Myrciaria dubia) showed HIF inhibitory effects determined by luciferase assays. Camu-camu downregulated HIF-1α and VEGFA mRNA expressions in a concentration-dependent manner. Camu-camu also inhibited HIF-1α protein expressions, and its inhibitory effect was greater than that of vitamin C, which is present at high levels in camu-camu. The camu-camu extract suppressed the activation of HIF and VEGF in RPE cells. This could assist anti-VEGF therapy in patients with abnormal ocular neovascularization.

К вопросу о резистентности диабетического макулярного отека

Purpose. To evaluate the morphofunctional features of diabetic macular edema (DME) and propose a classification of the degree of its resistance. Material and methods. The study included 448 patients (448 eyes) with newly diagnosed DME. A complete ophthalmological examination was performed, including spectral optical coherence tomography of the macular area. All patients were divided into 3 study groups depending on the anti-VEGF drug used: Brolucizumab (138), Ranibizumab (142) and Aflibercept (168). All patients (110) resistant to loading doses of an anti-VEGF drug were switched to intravitreal administration of a dexamethasone-containing implant. The observation period was 6 months. Results. According to the results of our study, the overall percentage of resistance to anti-VEGF therapy in patients with DME was 24.6%. At the same time, in group 1 it was observed in 20.2% of patients, in group 2 in 28.1% and in group 3 in 25.0%. It was found that when switching to intravitreal administration of a dexamethasone-containing biodegradable implant, there was an increase in visual acuity in the studied groups, respectively, from 0.25 to 0.67, from 0.04 to 0.3 and from 0.38 to 0.6 against the background of a decrease in retinal edema. Conclusion. The use of a dexamethasone-containing biodegradable implant after 6 months improved the architectonics of the retinal layers, increased visual acuity and reduced retinal edema in group 1 in 92.9% of patients, in group 2 in 87.5% and in group 3 in 90.5%. The developed clinical classification of the degree of DME resistance, depending on the morphofunctional features of the patient's retina, contributes to making the optimal decision regarding the choice of the most effective initial intravitreal pharmacotherapy for this disease. Key words: diabetic macular edema, anti- VEGF drugs, classification of DME resistance to intravitreal pharmacotherapy, dexamethasone implant

Maintenance of Vision Needed to Drive after Intravitreal Anti-VEGF Therapy in Patients with Neovascular Age-related Macular Degeneration and Diabetic Macular Edema

To evaluate the association between intravitreal anti-VEGF therapy and visual acuity (VA)/driving vision maintenance over 4 years in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME). Retrospective, observational, clinical practice cohort study using data from the Vestrum Health database. Initial diagnosis (January 1, 2014 to June 30, 2019) of nAMD or DME and ≥ 1 year of treatment/follow-up history. The VA analysis required 4 years of treatment/follow-up history. For the driving vision maintenance analysis, patients required Snellen VA of 20/40 or better at baseline and for ≥ 6 months during year 1 after index intravitreal anti-VEGF treatment in the better-seeing eye. A loss-of-driving event was the first clinic visit with VA worse than 20/40 sustained for ≥ 6 consecutive months. Kaplan-Meier analyses estimated the probability of maintaining driving vision over 4 years stratified by year-1 injection number. Cox proportional hazard models examined associations between baseline clinical characteristics and year-1 injection frequency and the risk of losing driving vision. Mean change in VA over time and by baseline VA, driving vision maintenance probability over time and stratified by anti-VEGF injection frequency, and baseline factors predictive of driving vision maintenance. In year 1, the nAMD and DME cohorts gained 8.5 and 9.5 ETDRS letters, respectively. Between years 1 and 4, patients with nAMD and DME lost 6.6 and 2.7 ETDRS letters, respectively. The probability of maintaining driving vision over 4 years was 56% (nAMD) and 72% (DME); among patients who received 1 to 5, 6 to 7, and ≥ 8 anti-VEGF injections in year 1, corresponding probabilities were 50%, 56%, and 65% (nAMD; P < 0.001) and 63%, 72%, and 77% (DME; P < 0.001). Baseline factors associated with driving vision loss included older age, worse index VA, geographic atrophy (nAMD), and worsening baseline diabetic retinopathy (DME). Older age and worse index VA were risk factors for driving vision loss, whereas a greater year-1 injection number was associated with driving vision maintenance through year 4, supporting early initiation and frequent anti-VEGF injections for maintaining driving vision in nAMD or DME. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Pre- and perioperative prophylaxis of anti-VEGF therapy in patients with exudative macular degeneration

Macular degeneration is one of the leading causes of blindness worldwide. Nowadays, the gold standard treatment for its exudative form is intravitreal injections with vascular growth factor inhibitor preparations performed on a once-daily basis. Great importance is now attached to the appropriate prophylaxis in the pre- and perioperative period in order to minimise the risk of complications, which often lead to irreversible damage to vision.

Outcomes and safety of subsequent treatments after immune- and anti-VEGF therapy in patients with metastatic clear-cell renal cell carcinoma: Outcomes from a tertiary referral hospital.

e16533 Background: Immune checkpoint inhibitors (ICIs) and anti-VEGFs, either in combination or sequentially, are the standard of care in first- and second-line (2L) setting for metastatic clear-cell renal cell carcinoma (mRCC); however, there is uncertainty about the subsequent lines. We describe real-world outcomes and safety of using anti-VEGFs such as cabozantinib (CABO), axitinib (AXI), and sunitinib (SUN) after ICIs and anti-VEGF therapies in patients (pts) with mRCC. Methods: A retrospective audit was performed on pts with mRCC treated between June 2014 and June 2022 at the St Bartholomew’s Hospital, London, UK. Baseline patient and treatment characteristics, best response, dose modifications and survival outcomes were collected. Kaplan-Meier methods were used to evaluate the progression-free survival (PFS) and overall survival (OS). Results: Overall, 188 pts with mRCC were treated. We analysed 69 pts of whom 45 (65%), 16 (23%) and 8 (12%) pts received CABO, AXI, and SUN, respectively, as subsequent treatment after prior ICIs and anti-VEG. Baseline characteristics are described. Median follow-up was 36 months (95% CI: 31.6 - 55.3). Overall, the partial response (PR) and stable disease (SD) rates were 9% and 45%, respectively. Eleven percent, 12% and 0% pts achieved PR and 53%, 25% and 31% achieved SD on CABO, SUN and AXI, respectively. In general, the median PFS was 9.9 months (95% CI: 6.5-14.2) and the median OS was 16.5 months (95% CI: 11.6-23.5). One-year PFS and 1-year OS was 36% and 51%, respectively. PFS and OS by treatment are reported. The number of pts who experienced toxicities that required dose reductions was higher with CABO (58%) and SUN (37%) than with AXI (6%). The median time to dose reduction was 2.4, 1.4, and 1.4 months for CABO, SUN and AXI. Conclusions: In our centre, CABO was the most common subsequent treatment after previous ICIs and anti-VEGF. Taking into account the retrospective and single-centre nature of the collected data these results support the activity of CABO, AXI and SUN in this setting. AXI was well tolerated with less dose modifications. [Table: see text]

Towards a population pharmacokinetic/pharmacodynamic model of anti-VEGF therapy in patients with age-related macular degeneration

PurposeTo develop a population pharmacokinetic/pharmacodynamic model (popPKPD) of intravitreal bevacizumab treatment for neovascular age-related macular degeneration (nAMD) patients to learn about the PK/PD relationship and utilise it for dosing regimen decisions on future nAMD patients. MethodsThe Greater Manchester Avastin for Neovascularisation (GMAN) randomised clinical trial data was retrospectively utilised, and the best-corrected visual acuity (BCVA) and central macular retinal thickness (CRT, measured by optical coherence tomography) were the PD inputs to the model. Using the nonlinear mixed-effects method, the best PKPD structural model was investigated, and the clinical significance of the two different dosing treatment regimens (as-needed versus routine) was evaluated. ResultsA structural model to describe the change of BCVA from the baseline of nAMD patients was successfully obtained based on the turnover PD model concept (drug stimulates the “visual acuity response production”). The popPKPD model and simulation indicate that the routine regimen protocol improves patient visual outcome compared to the as–needed protocol.For the change in CRT, the turnover structural PKPD model was too demanding to fit to the given clinical data. ConclusionsThis is the first popPKPD attempt in nAMD treatment that shows the potential of this strategy to understand/inform the dosing regimen. Clinical trials with richer PD data will provide the means to build more robust models.

Efficacy and safety profile of intravitreal dexamethasone implant versus antivascular endothelial growth factor treatment in diabetic macular edema: a systematic review and meta-analysis

To better understand the efficacy of intravitreal dexamethasone implant (Ozurdex) versus antivascular endothelial growth factor (anti-VEGF) treatment in patients with diabetic macular edema (DME). A systematic review and meta-analysis. The study included randomized control trials (RCTs) and non-randomized control trials (Non-RCTs) before December 2021 that compare the efficacy of Ozurdex-related therapyand anti-VEGF therapy. We searched PubMed, Cochrane Library, and EMBASE. The quality of the included studies was assessed carefully. 30 studies were included. Regarding BCVA change, the overall result revealed no significant differences between Ozurdex and anti-VEGF therapies in patients with nonresistant DME, but Ozurdex group had significantly more VA improvement than anti-VEGF therapies in patients with resistant DME (MD 0.12, 95% CI 0.02–0.21). In terms of central retinal thickness (CRT) decrease, there was a significant difference between Ozurdex therapy and anti-VEGF therapy in patients with nonresistant DME (MD 48.10, 95% CI 19.06–77.13) and resistant DME (MD 65.37, 95% CI 3.62–127.13). Overall, Ozurdex therapy resulted in significantly greater VA improvement and CRT decrease than anti-VEGF therapy in resistant DME patients. Ozurdex therapy was not inferior to anti-VEGF therapy in patients with nonresistant DME.

MP04-10 MACHINE LEARNING PREDICTS METABOLIC BIOMARKERS OF RESPONSE TO ANTI-VEGF DRUG SUNITINIB IN CCRCC

You have accessJournal of UrologyCME1 Apr 2023MP04-10 MACHINE LEARNING PREDICTS METABOLIC BIOMARKERS OF RESPONSE TO ANTI-VEGF DRUG SUNITINIB IN CCRCC Katiana Vazquez-Rivera, X. Amy Xie, Stephen Reese, Ritesh Kotecha, Martin Voss, Robert Motzer, Wesley Tansey, Ari Hakimi, and Ed Reznik Katiana Vazquez-RiveraKatiana Vazquez-Rivera More articles by this author , X. Amy XieX. Amy Xie More articles by this author , Stephen ReeseStephen Reese More articles by this author , Ritesh KotechaRitesh Kotecha More articles by this author , Martin VossMartin Voss More articles by this author , Robert MotzerRobert Motzer More articles by this author , Wesley TanseyWesley Tansey More articles by this author , Ari HakimiAri Hakimi More articles by this author , and Ed ReznikEd Reznik More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003215.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Clear cell renal cell carcinoma (ccRCC) is a metabolic disease with multiple mutated genes involved in the regulation of cellular metabolic processes, however it remains unknown how ccRCC metabolites are associated with response to anti-VEGF or immunotherapy agents. Metabolomic signatures may serve as a biomarker of response or serve as future points of intervention for targeted agents. Thus, we sought to characterize metabolite signatures associated with response to anti-VEGF therapy in patients with ccRCC. METHODS: A machine learning algorithm called T-MIRTH (Transcriptomics-Metabolite Imputation via Rank-Transformation and Harmonization) was developed to identify key metabolites. In short, this algorithm imputes metabolite abundances from RNA sequencing data by modeling metabolite-RNA covariation across datasets with paired metabolomics and transcriptomics data. 262 well-predicted metabolites were used to test the association between imputed levels of individual metabolites by T-MIRTH and progression free survival (PFS) in 7 published sunitinib clinical trials in advanced ccRCC. Using a multivariable Cox proportional hazard model, metabolomic signatures were correlated with progression-free survival and regression results were aggregated using a random effects meta-analysis model. RESULTS: Our T-MIRTH algorithm was validated using 3 ccRCC datasets with paired metabolomics and transcriptomics data and we demonstrated that T-MIRTH can accurately predict metabolite levels using RNA sequencing data. We then demonstrated using the ccRCC TCGA that T-MIRTH predicted metabolic differences between both tumor/normal samples and high/low-stage samples. Our algorithm was able to identify 262 validated metabolites. The results from our meta-analysis across 7 clinical trial demonstrated 7 metabolites significantly associated with improved PFS in the sunitinib arm (FDR < 0.05). In particular, high levels of 1-methylimidazole acetate had improved PFS within the sunitinib arm across all trials. CONCLUSIONS: Using a novel algorithm, we identified 7 metabolites that were associated with improved PFS in patients treated with sunitinib across 7 clinical trials. These metabolites may serve as biomarkers of response and may also be important targets for future therapeutics. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e37 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Katiana Vazquez-Rivera More articles by this author X. Amy Xie More articles by this author Stephen Reese More articles by this author Ritesh Kotecha More articles by this author Martin Voss More articles by this author Robert Motzer More articles by this author Wesley Tansey More articles by this author Ari Hakimi More articles by this author Ed Reznik More articles by this author Expand All Advertisement PDF downloadLoading ...

Анализ влияния отслойки ретинального пигментного эпителия при экссудативной форме возрастной макулярной дегенерации на долгосрочные результаты лечения

Retinal pigment epithelial detachments (RPE) develops in more than 80 % of eyes with exudative age-related macular degeneration (eAMD) [1, 2]. RPED is a pathological condition in which the retinal pigment epithelium separates from the underlying Bruch's membrane due to the formation of a fibrovascular membrane, drusenoid material, fluid and/ or blood accumulation [3]. Recent published data from studies have shown controversial results of treatment with anti-VEGF therapy in patients with ARD on the background of eAMD, possibly due to different diagnostic capabilities and interpretation of the results by specialists. Purpose. To study the response to anti-VEGF therapy in patients with various RPED in eAMD. Material and methods. The study included 221 patients: with serous vascular (55 eyes) and fibrovascular detachment of RPE (176 eyes). To determine the maximum height of the retinal pigment epithelium detachment, it was necessary to manually set a line from Bruch's membrane to the retinal pigment epithelium in the scan where the maximum detachment of the retinal pigment epithelium was detected. Antiangiogenic therapy was carried out using the drug Aflibercept (Eylea® / Eulea®, Bayer Pharma AG, Mullerstrasse 178, 13353 Berlin, Germany) according to the standard method using the treat &amp; extend regimen (treat and prolong). Results. A significant increase in BCVA was found in patients with 1st type neovascularization and PCV during the first year of therapy from 0.51 ± 0.18 to 0.58 ± 0.23 and from 0.66 ± 0.23 to 0.76 ± 0.20 (p &lt; 0.05), with a further gradual significant decrease and return from baseline BCVA by 3rd year to 0.51 ± 0.25 (p &lt; 0.05) in the group with 1st type CNV, in patients with PCV, there was also a decrease in BCVA, but this was unreliable. BCVA values in all four groups decreased by the 6th year of observation. There was a significant decrease in the height of RPED in the group with the 1st and 3rd types of neovascularization, as well as in patients with PCV during the first 2 years of therapy (p &lt; 0.05). Сonclusions. Thus, a significant increase in BCVA in the first year of therapy in patients with ARD is more common in 1st type CNV and with PCV. At the same time, in all groups, after 6 years of treatment, a downward trend in BCVA can be observed. Also, in all groups, there was a decrease in the height of RP, which indicates a good response of the fluid under RP to the ongoing anti-VEGF therapy. Keywords: exudative form of retinal pigment epithelium detachment, anti-VEGF therapy, aflibercept, retinal pigment epithelium detachment

Seven-year outcomes following intensive anti-vascular endothelial growth factor therapy in patients with exudative age-related macular degeneration

BackgroundAnti-vascular endothelial growth factor (VEGF) therapy is currently the most effective therapy of exudative age-related macular degeneration (AMD). The aim of this study was to assess long-term benefits of intensive aflibercept and ranibizumab anti-VEGF therapy in patients with exudative AMD.MethodsTwo clinical trial sites recruited their original subjects for a re-evaluation 7 years after the baseline visit of the phase-3 Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (VIEW 2) trial.Forty-seven eyes of 47 patients with AMD originally treated with ranibizumab (14 eyes) or aflibercept (33 eyes) were included.ResultsMean number of injections was 17.8 ± 3.0 during participation in the VIEW 2 trial. Fourteen of 47 (30%) eyes were given additional injections with a mean number of 5.7 ± 4.5 after the trial. At a mean follow-up time of 82 ± 5 months best corrected visual acuity (BCVA) remained stable or improved (≤ 10 letters lost) in 55% of patients in the entire study population, in 43% in the ranibizumab group and in 60% in the aflibercept group. In both groups combined mean BCVA was 54 ± 13 letters at baseline, 65 ± 17 letters at the end of the intensive phase and 45 ± 25 letters at the end of follow-up. There was no statistically significant difference in BCVA between the two groups at baseline (p = 0.88) and at the end of follow-up (p = 0.40). Macular atrophy was observed in 96% of eyes, average area was 7.22 ± 6.31 mm2 with no statistically significant difference between groups (p = 0.47). Correlation between BCVA at end-of-follow-up and the area of atrophy was significant (p < 0.001). At the end of follow-up, fluid was detected in 7 of 47 eyes (15%) indicating disease activity.ConclusionLong-term efficacy of aflibercept and ranibizumab was largely consistent. Following a two-year intensive therapy with as-needed regimen, BCVA was maintained or improved in almost half of the patients and in the ranibizumab group and more than half of the patients in the aflibercept group with very few injections. In a remarkable proportion of eyes, BCVA declined severely which underlines the need for long-term follow-ups and may indicate a more prolonged intensive therapy.Trial registrationsVIEW 2 study: ClinicalTrials.gov ID: NCT00637377, date of registration: March 18, 2008.Long-term follow-up: IRB nr.: SE RKEB 168/2022, ClinicalTrials.gov ID: NCT05678517, date of registration: December 28, 2022, retrospectively registered.

OCT生物标志物与DME患者抗VEGF治疗预后的相关性

OCT生物标志物与DME患者抗VEGF治疗预后的相关性

Evaluation of microaneurysms as predictors of therapeutic response to anti-VEGF therapy in patients with DME.

Administration of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is the first-line therapy for diabetic macular oedema (DME). However, some patients show no or insufficient response to repeated anti-VEGF injections. Therefore, it is necessary to identify factors that can predict this resistance against anti-VEGF treatment. Presence of microaneurysms (MAs) is a predictor of the development and progression of DME, but its relationship with the treatment response to the anti-VEGF agents is not well known. Therefore, we aimed to elucidate the relationship between the distribution of MAs and the response to anti-VEGF therapy in patients with DME. The number of MAs was measured before anti-VEGF therapy in each region using fluorescein angiography, indocyanine green angiography (IA), and optical coherence tomography angiography. Patients with DME were divided into the responder and non-responder groups after three loading phases. Differences in the distribution of MAs between the groups were investigated. Pre-treatment IA revealed more MAs in the nasal area in the non-responder group than in the responder group (10.7 ± 10.7 and 5.7 ± 5.7, respectively, in the nasal macula) (1.4 ± 2.1 and 0.4 ± 0.7, respectively, in the nasal fovea). Whereas, pre-treatment FA and OCTA could not reveal significantly difference between the groups. Detection of MAs in the nasal macula using pre-treatment IA may indicate resistance to anti-VEGF therapy. We recommend the clinicians confirm the presence of MAs in the nasal macula, as shown by IA, as a predictor of therapeutic response to anti-VEGF therapy in patients with treatment naive DME.

45-OR: Less Favorable Response to Anti-VEGF Therapy in Patients with Diabetic Macular Edema and Decreased Baseline Outer Retinal Layer Thickness

Early identification of patients who are more likely to respond to anti-VEGF therapy for diabetic macular edema (DME) would improve patient management and allow for more rapid assessment of new therapeutic targets. This study evaluated retinal thickness variables and their association with anti-VEGF therapy response in patients with DME. We identified patients at the Joslin Diabetes Center who received their first anti-VEGF injection for DME between 1/2016-12/20 and assessed mean change in visual acuity (VA) and central retinal thickness (RT) at 6 mos. A good VA or RT response to anti-VEGF therapy was defined using thresholds of letter and retinal thickness change as follows: eyes with baseline VA of ≥20/32, ≥5 letters; 20/40-20/70, ≥letters; ≤20/80, ≥15 letters and eyes with baseline RT of &amp;lt;375µm, &amp;gt;10%; 375-449µm, &amp;gt;20%; &amp;gt;449µm, &amp;gt;25%. A total of 151 eyes from 126 patients fell into the following responder groups: both VA and RT response (32.5%) , only VA response (21.9%) or RT response (11.3%) , and neither VA nor RT response (34.4%) , with 57.0% of all eyes exhibiting VA response and 43.7% exhibiting RT response. While diabetes duration, A1c, and blood pressure were not associated with responder group, decreased baseline thickness of the outer retinal layer (ORL) was more likely to be present in eyes with neither VA nor RT response (β=-.018; 95% CI -0.03 to -0.01; P=.006) . Improvement in mean VA was associated with younger age (β=.004; 95% CI 0.001-0.007; P=.01) . Decreased baseline ORL thickness (β=-.003; 95% CI -0.0to -0.001; P=.01) and increased baseline inner retinal layer (IRL) thickness (β=.0004; 95% CI 0.0001-0.0007; P=.02) were associated with less VA gain at 6 mos. These findings suggest that decreased baseline ORL thickness is associated with less favorable outcome after anti-VEGF therapy and may be a potential biomarker for treatment response in patients with DME. Disclosure M.G.Mitzner: None. W.Fickweiler: None. D.B.Robinson: None. T.Boumenna: None. L.P.Aiello: Consultant; KalVista Pharmaceuticals, Inc., Novo Nordisk, Stock/Shareholder; KalVista Pharmaceuticals, Inc. J.Sun: Consultant; American Diabetes Association, American Medical Association, Research Support; Adaptive Sensory Technology, Boehringer Ingelheim International GmbH, Genentech, Inc., Jaeb Center for Health Research, Janssen Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Optovue, Incorporated, Physical Sciences, Inc, Roche Pharmaceuticals. Funding American Diabetes Association (7-21-PDF-022) ; National Eye Institute (R01EYE26080-01) ; National Institute of Diabetes and Digestive and Kidney Diseases and National Institutes of Health (DP3-DK-094333-01) ; JDRF (17-2013-310) ; The Dianne Nunnally Hoppes Fund; The Beatson Pledge Fund

Морфофункциональные исходы при несоблюдении режима антиангиогенной терапии при неоваскулярной форме возрастной макулярной дегенерации у пациентов с низким функциональным статусом

Purpose. To study morphological and functional outcomes in patients with neovascular age-related macular degeneration (nAMD) and low visual acuity violating the treatment regimen. Material and methods. Treatment-naive patients as well as patients receiving anti-VEGF therapy with best-corrected visual acuity (BCVA) less than 0.1 were included. Demographic characteristics, changes in BCVA, central retinal thickness (CRT) and structural changes on optical coherence tomography (OCT) were evaluated baseline and at the of the study period. Results. BCVA changed not statistically significantly at the end of the study period in all groups (р &gt; 0.05). A statistically significant decrease of CRT was found only in the group of treatment-naive patients (р = 0.03). Atrophy of the retinal pigment epithelium and subretinal fibrosis were most common among structural changes in advanced nAMD with low visual acuity. These morphological changes persisted by the end of the observation period, without statistically significant changes in the frequency of occurrence. Conclusion. Low visual acuity in patients with advanced nAMD is associated with severe irreversible structural changes in the macula. The use of anti-VEGF therapy in patients with low functional status and severe changes in the macula appears to be unpromising. Keywords: age-related macular degeneration, antiangiogenic therapy, optical coherence tomography, retinal pigment epithelium atrophy, subretinal fibrosis.

LESSONS LEARNED FROM PACORES IN PROLIFERATIVE DIABETIC RETINOPATHY MANAGEMENT, DATA FROM LATIN AMERICA AND SPAIN: The Asbury Lecture 2020.

To review the current literature on the management of proliferative diabetic retinopathy (PDR) and the challenges in the real-world setting. A review of the literature was performed on the therapeutic options for PDR, with a focus on the real-world data presented by the Pan-American Collaborative Retina Study Group. Data from clinical trials and previous literature have reported that intravitreal antivascular endothelial growth factor (anti-VEGF) therapy is noninferior to the gold standard panretinal photocoagulation for treating PDR. However, PDR recurs rapidly after cessation of anti-VEGF therapy. This is especially important in the context of the diabetic population that is prone to loss to follow-up. In a real-world, prospective study, patients with prior panretinal photocoagulation followed by anti-VEGF therapy had higher rates of sustained PDR regression relative to anti-VEGF therapy alone. Owing to its transient therapeutic effect, anti-VEGF therapy in patients with diabetes can present a risk of recurrent retinal neovascularization and progression of PDR if follow-up cannot be guaranteed. A combined paradigm with less aggressive, immediate panretinal photocoagulation followed by anti-VEGF therapy should be considered in this population.

Complications After Anti-VEGF Therapy in Patients with Wet Form of AMD

Anti-VEGF therapy is the main treatment in patients with the wet form of AMD. Although successful in most cases, prolonged use of intravitreal therapy can lead to serious complications. The aim of this study is to present the possible longterm complications of anti-VEGF therapy in patients with the wet form of AMD, as well as the ways to prevent them. Methods: In our study, we included 32 patients with a wet form of AMD. They were all examined ophthalmologically in detail for VA, fundus color photography, OCT (Revue, Optovue) and OCT-A (Angiophlex, Zeiss). All patients were treated with aflibercept (Eylea) - according to the Treat and Extend scheme for a period of 2 years. They were followed for complications for a period of 2 years. Results: In the long run we observed the following complications expressed in %: tachyphylaxis to the drug substance – 20%; tears of RPE-10%; fibrosis and scarring - 45%; retinal atrophy 25%. In 20% of the observed patients we found tachyphylaxis after the first year, which led to a decrease in the effectiveness of treatment. In 10% of cases we observed rupture of RPE. This occurred mainly in patients with previous detachment of RPE with a large area and height. Retinal fibrosis developed in patients with macular hemorrhage, low VA, refractory retinal cysts, or cases of RAP. Retinal fibrosis usually appeared after 10 injections. These are patients with low initial visual acuity, thin choroid especially subfoveolar and usually occurred after a small number of intravitreal injections. Conclusion: Complications after anti-VEGF therapy are relatively rare, but always associated with very serious visual impairment. The stronger the effect of the anti-VEGF drug, the more common the complications, especially retinal fibrosis. Early detection of risk factors such as low initial vision, refractory retinal cysts, macular hemorrhage, large neovascular membrane, are a prerequisite for successful prevention and treatment of these complications.

Preferred treatment regimen of aflibercept after treatment interruption in patients with neovascular age-related macular degeneration

BACKGROUND: The efficacy of antiangiogenic therapy in neovascular age-related macular degeneration depends on adherence to the intravitreal injection regimen and regular follow-up. In 2020, the COVID-19 pandemic and associated epidemiological restrictions in ophthalmological care delivery led to a massive lack of appropriate control and management of this condition.&#x0D; AIM: To determine the preferred regimen of intravitreal anti-VEGF therapy in patients with neovascular age-related macular degeneration who experienced treatment interruption due to the COVID-19 pandemic.&#x0D; MATERIAL AND METHODS: Thirty eyes of 26 patients (20 males and 6 females, mean age 73.7 10.4 years) with neovascular age-related macular degeneration were included; all of them experienced treatment interruption due to the COVID-19 pandemic during the second year of aflibercept therapy. Re-starting therapy, all patients were divided in two groups and received treatment as per the fixed dosing (bimonthly), or as pro re nata (PRN) regimen. All patients underwent standard ophthalmological examination and optical coherence tomography before and after treatment interruption as well as six months after treatment re-start.&#x0D; RESULTS: At six months after treatment re-start, best corrected visual acuity and central retinal thickness did not show statistically significant difference similar between the fixed dosing group and that of PRN dosing regimen (p = 0.34 and p = 0.85, respectively). However, patients of the fixed dosing group received for one more injection than those of the PRN group (median value 2.0 injections, 95% confidence interval 2.0-2.4; p = 0.0001). Preservation of the disease activity according to optical coherence tomography data, in the fixed regimen group was found in 10 eyes (71.4 %) versus 9 eyes (56.2 %) in the PRN group (p = 0.63).&#x0D; CONCLUSIONS: For neovascular age-related macular degeneration patients at the second year of treatment, an adequate therapeutic strategy for re-starting anti-VEGF therapy after treatment interruption appears to be the PRN regimen. PRN regimen allows reducing one injection in comparison to fixed dosing regimen with comparable functional outcomes during first 6 month.

Efficacy of Anti-Vascular Endothelial Growth Factor Treatment in Neovascular Age-Related Macular Degeneration and Systemic Cardiovascular Risk Factors.

This study evaluates whether the presence of cardiovascular risk factors (CRFs) affects functional and morphological responses to anti–vascular endothelial growth factor (VEGF) therapy in patients with neovascular age-related macular degeneration (nAMD). Retrospective analysis included 98 treatment-naïve eyes followed for at least 12 months. Patients received intravitreal injections of ranibizumab or aflibercept with the dosage and regimen set according to each manufacturer’s recommendations for their product. Parameters evaluated at each follow-up visit included best-corrected visual acuity and central retinal thickness. Additionally, the presence of the following CRFs was evaluated: male sex, age of older than 70 years, history of current or past smoking, systemic arterial hypertension, diabetes mellitus, total hypercholesterolemia, low-density lipoprotein hypercholesterolemia, high-density lipoprotein concentration of 45 mg/dL or less, atherogenic dyslipidemia, family history of cardiovascular disease, and chronic kidney disease. A statistically significant better letter gain in visual acuity (p = 0.012) and greater percentage of responders (p = 0.035)—that is patients in whom best corrected visual acuity was stabilized or improved at 12 months—were noted among patients without a diagnosis of arterial hypertension. A statistically significant better mean visual improvement was also achieved in patients with higher total cholesterol plasma levels (p = 0.004), but this finding was not reflected in the significantly higher percentage of responders. The presence of remaining analyzed risk factors did not substantially affect the results of treatment. Systemic arterial hypertension is an independent factor leading to a poor functional outcome following anti-VEGF therapy in patients with nAMD. Effects of anti-VEGF treatment in patients with high total cholesterol levels should be analyzed in further research.