Anti-vascular Endothelial Growth Factor Research Articles

The efficacy of intravitreal anti-VEGF for radiation maculopathy: a systematic review and meta-analysis.

Anti-vascular endothelial growth factor (VEGF) therapy is the primary approach for managing radiation maculopathy. However, a noticeable gap exists in meta-analyses evaluating the efficacy of anti-VEGF therapy specifically in the context of radiation maculopathy. We conducted a review of comparative studies on anti-VEGF treatment up to October 2023. References were sourced from PubMed, EMBASE, and the Cochrane Library. The Cochrane Risk of Bias tool assessed the quality of randomized controlled trials (RCTs), while the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool evaluated non-RCTs. Thirteen articles originating from eleven trials involving 2,525 eyes of 2408 patients were included. Four trials with 2226 eyes examined the effect of preventive anti-VEGF. Four trials with 189 eyes assessed the effect of anti-VEGF for preexisting maculopathy, and three trials with 110 eyes compared different anti-VEGF treatment modalities. In the preventive anti-VEGF treatment meta-analysis over a 24-month follow-up, the anti-VEGF group exhibited significantly fewer cases of radiation maculopathy (OR: 0.40; 95% CI: 0.25, 0.66, P= .0003, I2 =45%). For the meta-analysis of anti-VEGF treatment for pre-existing radiation maculopathy over a 6-month follow-up, the anti-VEGF group showed improved visual acuity (SMD: -1.13, 95% CI: -1.69 to -0.56, P < .0000, I2 = 47%) and decreased central macular thickness (SMD: -0.59, 95% CI: -1.13 to -0.05, P = 0.03, I2 = 62%). Prophylactic anti-VEGF effectively prevents radiation maculopathy and is also beneficial in treating pre-existing radiation maculopathy. Intensive treatment initially provides early benefits, but the efficacy diminishes after transitioning to a treat-and-extend regimen.

Safety and tolerability of immune checkpoint inhibitors in people with HIV infection and cancer: insights from the national prospective real-world OncoVIHAC ANRS CO24 cohort study

BackgroundImmune checkpoint inhibitors (ICIs) have been a major advance in cancer management. However, we still lack prospective real-world data regarding their usage in people with HIV infection (PWH).MethodsThe ANRS CO24...

Outcomes of Pro Re Nata versus Treat-and-Extend Anti-VEGF Injections for Myopic Macular Neovascularization in Multiethnic Patients in the United States.

To compare visual outcomes and recurrence rates between pro re nata (PRN), treat-and-extend and stop (TES), and treat-and-extend with chronic maintenance dosing (TEM) regimens of anti-vascular endothelial growth factor (VEGF) injections for myopic macular neovascularization (MNV) in multiethnic patients. This retrospective study included patients treated with PRN, TES, or TEM for myopic MNV using intravitreal bevacizumab or ranibizumab. The primary outcome measure was visual improvement at 12 months. We included 127 eyes of 117 patients (75 females and 42 males). The mean follow-up duration was 37.9 months. We compared the outcomes of PRN (47 eyes [37%]), TES (52 eyes [41%]), and TEM (28 eyes [22%]). All groups showed significant visual improvement at 12 months and at the final follow-up (all P<0.05). Visual outcomes did not differ significantly between the three groups at 12 months and final follow-up (all P>0.05). However, the number of eyes with recurrences was significantly higher in the PRN group and significantly lower in the TEM group during follow-up (38%, 21%, and 11% in the PRN, TES, and TEM groups, respectively; P=0.020). The PRN group received the fewest injections during follow-up (5.3, 10.9, and 19.9 injections in the PRN, TES, and TEM groups respectively; P<0.001). Anti-VEGF injections with PRN, TES, or TEM regimens are effective for myopic MNV and have comparable visual outcomes. Since PRN provides favorable outcomes with fewer injections, it should be the first-line approach. However, a treat-and-extend approach with TES and TEM may be an option given individual patient factors.

Multimodal imaging diagnosis and analysis of prognostic factors in patients with adult-onset Coats disease.

To describe the multimodal imaging features, treatment, and outcomes of patients diagnosed with adult-onset Coats disease. This retrospective study included patients first diagnosed with Coats disease at ≥18 years of age between September 2017 and September 2021. Some patients received anti-vascular endothelial growth factor (VEGF) therapy (conbercept, 0.5 mg) as the initial treatment, which was combined with laser photocoagulation as needed. All the patients underwent best corrected visual acuity (BCVA) and intraocular pressure examinations, fundus color photography, spontaneous fluorescence tests, fundus fluorescein angiography, optical coherence tomography (OCT), OCT angiography, and other examinations. BCVA alterations and multimodal image findings in the affected eyes following treatment were compared and the prognostic factors were analyzed. The study included 15 patients who were aged 24-72 (57.33±12.61)y at presentation. Systemic hypertension was the most common associated systemic condition, occurring in 13 (86.7%) patients. Baseline BCVA ranged from 2.0 to 5.0 (4.0±1.1), which showed improvement following treatment (4.2±1.0). Multimodal imaging revealed retinal telangiectasis in 13 patients (86.7%), patchy hemorrhage in 5 patients (33.3%), and stage 2B disease (Shield's staging criteria) in 11 patients (73.3%). OCT revealed that the baseline central macular thickness (CMT) ranged from 129 to 964 µm (473.0±230.1 µm), with 13 patients (86.7%) exhibiting a baseline CMT exceeding 250 µm. Furthermore, 8 patients (53.3%) presented with an epiretinal membrane at baseline or during follow-up. Hyper-reflective scars were observed on OCT in five patients (33.3%) with poor visual prognosis. Vision deteriorated in one patient who did not receive treatment. Final vision was stable in three patients who received laser treatment, whereas improvement was observed in one of two patients who received anti-VEGF therapy alone. In addition, 8 of 9 patients (88.9%) who received laser treatment and conbercept exhibited stable or improved BCVA. Multimodal imaging can help diagnose adult-onset Coats disease. Anti-VEGF treatment combined with laser therapy can be an option for improving or maintaining BCVA and resolving macular edema. The final visual outcome depends on macular involvement and the disease stage.

Variceal bleeding following treatment with atezolizumab plus bevacizumab in two patients with unresectable hepatocellular carcinoma.

Bleeding-related adverse events may occur due to anti-vascular endothelial growth factors. Here, we report two cases of variceal rupture during atezolizumab plus bevacizumab (ATZ/BV) treatment for unresectable hepatocellular carcinoma (u-HCC).Case 1 involved a man in his 60s with alcoholic liver cirrhosis (LC) and u-HCC. Seventy-four days after ATZ/BV administration, the patient was admitted for hematemesis. Upper esophagogastroduodenoscopy (EGD) revealed worsening of the esophageal varices (EVs) to F2 grade with active bleeding. Endoscopic variceal ligation successfully achieved hemostasis.Case 2 involved a man in his 70s with alcoholic LC and u-HCC. The patient was admitted with hematemesis 114days after ATZ/BV administration. During EGD, the EVs deteriorated to F3 grade, although hemostasis had already been achieved. The evaluation was discontinued during the observation stage because of the worsening hepatic reserve.Neither patient had EVs warranting prophylactic treatment before ATZ/BV administration, showed a partial tumor response, or had portal vein tumor thrombus. Both patients demonstrated increased total diameters of the collateral veins and splenic volume compared to those before treatment. These findings suggest that ATZ/BV treatment may increase portal pressure. In conclusion, the administration of ATZ/BV to patients with LC and u-HCC necessitates careful management of EVs aggravation and rupture.

Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1.

Bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, inhibits angiogenesis and reduces tumor growth. Serum VEGF-C, lactate dehydrogenase, and inflammatory markers have been reported as predictive markers related to bevacizumab treatment. Programmed cell death ligand 1 (PD-L1) could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis. To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer (CRC) according to the expression of PD-L1. This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24, 2014 and February 28, 2022, at Samsung Medical Center (Seoul, South Korea). Analysis of patient data included evaluation of PD-L1 expression by the combined positive score (CPS). We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC. A total of 124 patients was included in this analysis. Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy. While 77% of patients received FOLFOX, 23% received FOLFIRI as backbone first-line chemotherapy. The numbers of patients with a PD-L1 CPS of 1 or more, 5 or more, or 10 or more were 105 (85%), 64 (52%), and 32 (26%), respectively. The results showed no significant difference in progression-free survival (PFS) and overall survival (OS) with bevacizumab treatment between patients with PD-L1 CPS less than 1 and those with PD-L1 CPS of 1 or more (PD-L1 < 1% vs PD-L1 ≥ 1%; PFS: P = 0.93, OS: P = 0.33), between patients with PD-L1 CPS less than 5 and of 5 or more (PD-L1 < 5% vs PD-L1 ≥ 5%; PFS: P = 0.409, OS: P = 0.746), and between patients with PD-L1 CPS less than 10 and of 10 or more (PD-L1 < 10% vs PD-L1 ≥ 10%; PFS: P = 0.529, OS: P = 0.568). Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.

Short-term Outcomes of Faricimab for Neovascular Age-related Macular Degeneration with Limited Response to Ranibizumab or Aflibercept

Purpose: To evaluate the clinical outcomes of switching to faricimab for patients with neovascular age-related macular degeneration (AMD) demonstrating a limited response to prior anti-vascular endothelial growth factor (VEGF) treatments.Methods: We performed a retrospective analysis of patients with neovascular AMD who had residual subretinal fluid (SRF) or intraretinal fluid (IRF) despite treatment with ranibizumab or aflibercept, and who were subsequently treated with faricimab. The study assessed changes in best-corrected visual acuity (logarithm of the minimum angle of resolution) and central retinal thickness (CRT), as well as differences in the incidence of SRF, IRF, and serous retinal pigment epithelial detachment (S-PED) with versus without switching to faricimab.Results: The study included 22 eyes. Mean best-corrected visual acuity improved from 0.31 ± 0.21 before switching to faricimab to 0.28 ± 0.19 after the switch (&lt;i&gt;p&lt;/i&gt; = 0.172). CRT significantly decreased from 336.7 ± 83.3 to 279.9 ± 51.1 μm (&lt;i&gt;p&lt;/i&gt; = 0.002). Prior to switching, SRF was noted in 17 patients (94.4%), IRF in 5 (27.8%), and S-PED in 4 (22.2%). Following the switch to faricimab, these figures dropped to 13 (72.2%), 4 (22.2%), and 3 (16.7%), respectively. A complete resolution of retinal edema was achieved in four patients (22.2%) after the treatment switch.Conclusions: Switching to faricimab in patients with neovascular AMD who had a limited response to previous treatments led to significant anatomical improvements. Faricimab may be a valuable treatment option for these patients.

Optimizing Diabetic Macular Edema Treatment: A Meta-Analysis of Subthreshold Micropulse Laser and Anti-Vascular Endothelial Growth Factor Combination Therapy.

Background: Diabetic macular edema (DME) is the primary cause of visual impairment in individuals with diabetes. Anti-vascular endothelial growth factor (VEGF) is the current first-line treatment for DME owing to its effectiveness. However, frequent anti-VEGF injections may be inconvenient for patients. Therefore, this study aimed to investigate whether the addition of subthreshold micropulse laser (SML) to anti-VEGF therapy could reduce the requirement for anti-VEGF injections while maintaining the treatment efficacy for DME. Methods: Clinical trials retrieved from the databases of PubMed, EMBASE, and the Cochrane Library were evaluated to determine the effectiveness of combination treatment with SML and anti-VEGF medication compared with that of anti-VEGF treatment alone. The primary outcome measures were the changes in CMT, best-corrected visual acuity (BCVA), and the total number of intravitreal injections (IVIs). Results: The IVI + SML group revealed a substantial increase in the logarithm of the minimum angle of the resolution BCVA and a reduction in CMT at the 12-month follow-up (BCVA: random-effects; mean difference [MD], -0.05; 95% confidence interval [CI]: -0.10 to -0.01; p-value = 0.28, and CMT: random-effects; MD, -18.27; 95% confidence interval, -27.36 to -9.18; p-value = 0.20). The number of required IVIs in the IVI + SML group was lower than that in the IVI only group (random-effects; MD, -2.22; 95% CI: -3.13 to -1.31; p-value < 0.01). Conclusions: Combining SML therapy with anti-VEGF injections may reduce the total number of injections required, improve VA, and reduce CMT at the 12-month follow-up. Although the included studies used different SML regimens and anti-VEGF agents, this review indicates that the application of additional SML therapy results in positive clinical outcomes.

Molecular Responses of Anti-VEGF Therapy in Neovascular Age-Related Macular Degeneration: Integrative Insights From Multi-Omics and Clinical Imaging.

The purpose of this study was to investigate the molecular mechanisms underlying anti-vascular endothelial growth factor (anti-VEGF) efficacy and response variability in neovascular age-related macular degeneration (nAMD) using longitudinal proteomic and metabolomic analysis alongside three-dimensional lesion measurements. In this prospective study, 54 treatment-naive patients with nAMD underwent "3+ pro re nata" (3+PRN) anti-VEGF regimens followed for at least 12 weeks. Aqueous humors were collected pre- and post-treatment for proteomic and metabolomic analysis. Three-dimensional optical coherence tomography (OCT) and OCT angiography assessed different types of nAMD lesion volumes and areas. There were 1350 proteins and 1268 metabolites that were identified in aqueous humors, with 301 proteins and 353 metabolites significantly altered during anti-VEGF treatment, enriched in pathways of angiogenesis, energy metabolism, signal transduction, and neurofunctional regulation. Sixty-seven changes of (Δ) molecules significantly correlated with at least one type of ΔnAMD lesion. Notably, proteins FGA, TALDO1, and ASPH significantly decreased during treatment, with their reductions correlating with greater lesion regression in at least two lesion types. Conversely, despite that YIPF3 also showed significant downregulation, its decrease was associated with poorer regression in total nAMD lesion and subretinal hyper-reflective material. This study identifies FGA, TALDO1, and ASPH as potential key molecules in the efficacy of anti-VEGF therapy, whereas YIPF3 may be a key factor in poor response. The integration of longitudinal three-dimensional lesion analysis with multi-omics provides valuable insights into the mechanisms and response variability of anti-VEGF treatment in nAMD.

Systemic effects of anti-VEGF intravitreal injection in patients with age-related macular degeneration: A multi-institutional real-world study.

In individuals aged >50 years, age-related macular degeneration (AMD) is the leading cause of irreversible blindness. Intravitreal injections of antivascular endothelial growth factor (VEGF) agents (bevacizumab, ranibizumab, and aflibercept) show good efficacy and similar incidences of systemic adverse events (SAEs). However, comparative studies between agents are limited. Our study aimed to compare the real-world SAE risks of bevacizumab, ranibizumab, and aflibercept users. This retrospective cohort study identified new bevacizumab, ranibizumab, and aflibercept users in a multi-institutional database in Taiwan between 2014 and 2019. Inverse probability of treatment weights (IPTW) with propensity scores was conducted to achieve homogeneity among groups. The Fine and Gray model was utilized to estimate the subdistribution hazard ratio and 95% confidence interval. This study included 701 bevacizumab, 463 ranibizumab, and 984 aflibercept users. After IPTW, all covariates were well-balanced. All three anti-VEGF agents had a low and comparable number per 100 person-years of major adverse cardiac events, heart failure, thromboembolic events, major bleeding, all-cause admission, and all-cause death (all P > 0.05). No significant differences in long-term change of systolic and diastolic blood pressure, low-density lipoprotein, estimated glomerular filtration rate, and alanine transaminase (all P for interaction > 0.05) were observed among groups. Bevacizumab, ranibizumab, and aflibercept had a good systemic safety profile in this study. All groups showed a low and similar SAE risk and no differences in their long-term change of laboratory data. Therefore, these anti-VEGF agents could be prescribed safely to patients with AMD.

Cellular and Biomaterial Approaches for Treating Age-Related Macular Degeneration

Tissue Engineering offers a novel, curative approach to treating Age-Re-lated Macular degeneration (AMD), a disease characterized by excessive drusen depo-sition beneath the retinal surface and consequent vision loss. Preclinical studies in rats have shown that transplanted Retinal Pigment Epithelium (RPE) derived from human Embryonic Stem Cells (hESC) have not only slowed AMD but have also restored vision. There are two main methods of delivering RPE cells: direct injection and monolayer surgical insertion, the latter demonstrating long-term integration. Biocompatible scaf-folds allow for better delivery of RPE cells, induced Pluripotent Stem Cells (iPSC), and Retinal Progenitor Cells (RPC). Unlike animal-derived extracellular matrix components, soft modulus biomaterials such as poly(lactic-co-glycolic acid) (PLGA) and poly(l-lactic acid) (PLLA) are ideal for AMD cell transplants because of fast degradation times, high cellular attachment proliferation, and strong adherence to Bruch’s membrane. These biomaterials can also be created at a 10-100μm thickness so that vision is not distorted. Use of biomaterials could be improved by cross-linking them with anti-vascular endothe-lial growth factors (VEGFs) like Brolucizumab and retinal growth factors such as fibro-blast growth factor (FGF). Similarly, hESC and iPSC cells can be genetically modified to secrete anti-VEGF factors.

Case report: heart failure related to intravitreal injection of anti-VEGF

BackgroundIntravitreal injection of anti-vascular endothelial growth factor is considered the first-line treatment for polypoidal choroidal vasculopathy. It has potential risks for circulatory system, which should be particularly carefully evaluated in older patients. In this case study, we aim to discuss the potential impact of this treatment regimen on cardiac health.Case presentationThis case report describes an elderly patient with no prior history of heart disease who exhibited unexpected heart enlargement and dysfunction. Throughout the patient’s hospital stay, various potential causes were investigated, leading to the hypothesis that a 10-year history of intravitreal injections of anti-vascular endothelial growth factor could be related to the observed clinical manifestations. The patient was advised to discontinue this treatment, and after a 2-month follow-up period, there was a gradual improvement in the patient’s cardiac structure and function.ConclusionThis manuscript highlights the importance of conducting cardiac examinations before and after anti-vascular endothelial growth factor treatment, especially for individuals at risk of heart diseases like the elderly. It emphasizes the need to carefully weigh the benefits and risks of treatment regimens to ensure optimal therapeutic outcomes.

Factors Affecting Disease Stability After Intravitreal Brolucizumab Injection for Refractory Neovascular Age-Related Macular Degeneration.

The purpose of this study is to identify the factors affecting neovascular age-related macular degeneration (nAMD) disease stability after brolucizumab treatment. We retrospectively analyzed the medical records of 31 patients (31 eyes) with recalcitrant nAMD who were switched to brolucizumab after conventional anti-vascular endothelial growth factor (VEGF) treatment. We divided patients into two groups by treatment extension (TE) period: group 1 with TE < 12weeks (N = 16) and group 2 with TE ≥ 12weeks (N = 15). We compared outcomes between the groups at 2, 4, 8, and 12weeks, including morphological characteristics of choroidal neovascularization (CNV). Logistic regression analysis identified factors associated with TE ≥ 12weeks. Group 2 had a significantly greater proportion of patients with dry macula (subretinal and intraretinal fluids absent) than group 1 (60 vs. 12.5%) at 2weeks (P < 0.05). Best-corrected visual acuity (BCVA) and subfoveal choroidal thickness (SFCT) did not differ significantly between groups at all timepoints. Central subfield retinal thickness (CST) was significantly lower in group 2 at 2 (237.1 vs. 280.8μm; P < 0.05), 4 (224.0 vs. 262.9μm; P < 0.05), and 8weeks (216.8 vs. 331.1μm; P < 0.05). Group 2 had less vessel area (0.63 vs. 1.27 mm2; P < 0.05) and total vessel length (0.22 vs. 0.42mm; P < 0.05). Choriocapillaris flow deficit (CCFd) was significantly lower in group 2 (42.7 vs. 48.2%; P < 0.05). Dry macula at 2weeks (odds ratio [OR] = 8.3; P < 0.05) and a lower CCFd (OR = 0.73; P < 0.05) were associated with TE ≥ 12weeks. Early fluid-free status after switching to brolucizumab and choriocapillary function around CNV were prognostic factors for disease stability in nAMD refractory to anti-VEGF treatment.

Cost-effectiveness Analysis of Ranibizumab Biosimilar for Neovascular Age-Related Macular Degeneration and its Subtypes from the Societal and Patient Perspectives in Japan.

This study evaluated the cost-effectiveness of anti-vascular endothelial growth factor (VEGF) therapies for subtypes of neovascular age-related macular degeneration (nAMD) from the societal perspective, and for any nAMD from the patient perspective in Japan. A Markov model was developed to simulate the lifetime transitions of a cohort of patients with nAMD through various health states based on the involvement of nAMD, the treatment status, and decimal best-corrected visual acuity. Ranibizumab biosimilar was compared with aflibercept from the societal perspective regardless of treatment regimen for the analysis of three subtypes (typical nAMD, polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP)). Two analyses from the patient perspective focusing on the treat-and-extend regimens were performed, one with a cap on patients' copayments and one without. Ranibizumab biosimilar was compared with branded ranibizumab, aflibercept, aflibercept as the loading dose switching to ranibizumab biosimilar during maintenance (aflibercept switching to ranibizumab biosimilar), and best supportive care (BSC), for patients with any nAMD. In the subtype analyses, ranibizumab biosimilar when compared with aflibercept resulted in incremental quality-adjusted life years (QALYs) of - 0.015, 0.026, and 0.009, and the incremental costs of Japanese yen (JPY) - 50,447, JPY - 997,243, and JPY - 1,286,570 for typical nAMD, PCV, and RAP, respectively. From the patient perspective, ranibizumab biosimilar had incremental QALYs of 0.015, 0.009, and 0.307, compared with aflibercept, aflibercept switching to ranibizumab biosimilar, and BSC, respectively. The incremental costs for ranibizumab biosimilar over a patient lifetime excluding the cap on copayment were estimated to be JPY - 138,948, JPY - 391,935, JPY - 209,099, and JPY - 6,377,345, compared with branded ranibizumab, aflibercept, aflibercept switching to ranibizumab biosimilar, and BSC, respectively. Ranibizumab biosimilar was demonstrated as a cost-saving option compared to aflibercept across all subtypes of nAMD, irrespective of the perspectives considered.

Comparison of Different Doses of Oral and Ocular Propranolol for Retinopathy of Prematurity: A Network Meta-Analysis.

The efficacy and safety of propranolol for retinopathy of prematurity (ROP) remain under debate. This network meta-analysis (NMA) focuses on whether a ranking may be established for different dose levels of propranolol as treatment of ROP in terms of stage progression as the primary outcome, with appearance of plus disease and need for anti-vascular endothelial growth factors (anti-VEGFs) or laser therapy as secondary endpoints. Fourteen studies (10 randomised controlled trials, three single-arm trials and one retrospective observational study) of 474 patients treated with oral or ocular propranolol were retrieved from databases up to April 2024. Meta-insight and model-based NMA were undertaken to evaluate the propranolol dose-response relationship. Studies were evaluated for model fit, risk of bias and Confidence of evidence In Network Meta-Analysis (CINeMA). Effect sizes were determined as odds ratio (OR) with 95% credible interval (CrI). Bayesian analysis showed a trend towards improved effects for propranolol given at late stages (stages 2-3; S23) of ROP progression compared with its administration at earlier stages (stages 0-1; S01). OR values for oral propranolol 1.5 and 2mg/kg/day given at S23 were 0.13 (95% CrI 0.04-0.37) and 0.16 (95% CrI 0.04-0.61), respectively, while given at S01 were 0.28 (95% CrI 0.02-2.96) and 0.78 (95% CrI 0.14-4.43), respectively. Similarly, OR of eye propranolol 0.2% at S23 was 0.37 (95% CrI 0.09-1.00) versus an S01 OR of 0.64 (95% CrI 0.21-2.04). Surface under the cumulative ranking curve (SUCRA) analyses confirmed best probability values for oral propranolol 1.5-2mg/kg followed by eye propranolol 0.2%, all at S23. Model-based NMA showed nonlinearity in the dose-response for oral propranolol with a trend to greater maximal effect for its administration at late versus early stages. For secondary endpoints, lower risk values were found with oral propranolol 1.5mg/kg/day at S23 for progression to plus disease (OR 0.14; 95% CrI 0.02-0.84) and need for anti-VEGFs (OR 0.23; 95% CrI 0.05-0.93) and laser (OR 0.16; 95% CrI 0.02-1.10) therapies also followed by eye propranolol 0.2%, and a similar profile was obtained with SUCRA analysis. Lower doses (0.5-1.0mg/kg/day) of oral propranolol retained efficacy. Threat of adverse events was estimated as risk difference versus control with no difference for eye propranolol 0.2% and oral propranolol 0.5mg/kg/day, modest increases of risk for oral propranolol 1.0 and 1.5mg/kg/day and the highest risk difference for oral propranolol 2.0mg/kg/day (0.06; 95% CI -0.01 to 0.13). A diminished risk of disease progression and need for additional treatment was obtained with propranolol in ROP, but safety is a potential concern. Propranolol eye micro-drops (0.2%) can be as efficacious as oral propranolol. Nonetheless, the evidence is limited due to the paucity and quality of the available studies.

Gastrointestinal Cancer Therapy and Cardiotoxicity.

Gastrointestinal cancers are a heterogenous group of cancers that share common risk factors with cardiovascular disease. Therapy for gastrointestinal cancers have improved cancer-specific outcomes at the cost of cardiotoxicity. The most common cardiotoxic therapies utilized in gastrointestinal cancers include conventional chemotherapy (including fluoropyrimidines and anthracyclines), targeted therapies including anti-vascular endothelial growth factor (VEGF) therapy and tyrosine kinase inhibitors (TKI), and immunotherapy. It is important for clinicians managing patients with gastrointestinal cancers to be aware of potential cardiotoxicity associated with these agents.

Subfoveal neurosensory detachment flattening and observe (SNF-Ob) approach for the management of Ci-DMO - a multicentric study.

To understand subfoveal neurosensory detachment flattening and observe (SNF-Ob) strategy and its relationship with visual acuity in the management of centre-involved diabetic macular oedema (Ci-DMO). This was a multicentric retrospective observational study. We reviewed data of 188 eyes of 130 patients who presented with Ci-DMO with subfoveal neurosensory detachment (NSD) and treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents or steroids. The primary outcome was best corrected visual acuity (BCVA) measured at the time of the first subfoveal neurosensory detachment flattening (SNF) and at the end of follow-up. Eyes that achieved 20/50 (LogMAR = 0.40) or better at first SNF had mean LogMAR BCVA 0.38 ± 0.21, 0.24 ± 0.11 and 0.21 ± 0.15 at baseline, at the time of first SNF, and at the end of the last follow-up respectively. Mean LogMAR BCVA significantly improved from baseline to first SNF (p < 0.0001; 95% CI 0.115-0.183) and at the end of the last follow-up (p < 0.0001; 95% CI 0.126-0.213) with a change of Early Treatment Diabetic Retinopathy Study (ETDRS) 10 letters. There was no significant difference in improvement in BCVA from the first SNF and at the end of the last follow-up (p = 0.0781; 95% CI -0.002 to 0.046). Eyes presenting with Ci-DMO and subfoveal NSD are unlikely to improve at SNF with BCVA > 20/50 (LogMAR = 0.40). Further evidence is needed before the combination of good BCVA and SNF may be considered as endpoint of pharmacological therapy for DMO.

Macular thickness and visual acuity are characterized by a quadratic nonlinear relation in previously treated neovascular AMD eyes.

To assess the associations between visual acuity (VA) and retinal thickness in age-related macular degeneration (AMD) eyes treated with anti-vascular endothelial growth factor (VEGF) therapy. Sixty-eight patients with neovascular AMD (68 eyes) undergoing anti-VEGF therapy with two years of follow-up imaging data after the initiation of treatment were retrospectively included. Linear and nonlinear regression analyses with curve fitting estimation were performed to explore the relationship between visual acuity and OCT-based parameters at the 3-month and 24-month follow-up visits. Regression analyses were also performed between visual acuity and the retinal thickness deviation which was calculated as the absolute value of the difference between measured and normative retinal thickness values. The VA was not associated with either foveal (R2 = 0.011 and p = .401 at 3 months; R2 = 0.032 and p = .142 at 24 months) or parafoveal (R2 = 0.045 and p = .081 at 3 months; R2 = 0.050 and p = .055 at 24 months) retinal thicknesses. Compared with the linear models, a quadratic function yielded a relative increase in the R2 coefficients. Conversely, the VA was linearly associated with foveal retinal thickness deviation (R2 = 0.041 and p = .037 at 24 months) and parafoveal retinal thickness deviation (R2 = 0.062 and p = .040 at 3 months; R2 = 0.088 and p = .014 at 24 months) values. Although there was no linear relationship between retinal thickness and VA, a weak but statistically significant linear relationship could be observed when a retinal thickness deviation was considered. This suggests that deviation-based parameters may be beneficial for structure-function correlations in the context of anti-VEGF therapy for neovascular AMD.

Treatment of Nocardia Chorioretinitis Related Choroidal Neovascularization with Aflibercept: A Case of Unveiled Immunocompromise with anti-GM-CSF Antibodies.

The purpose of this study was to describe a case of Nocardia chorioretinitis-related choroidal neovascularization (CNV) in a patient with anti-GM-CSF antibodies with resolution of choroidal neovascularization and visual recovery following a series of intravitreal anti-vascular endothelial growth factor. This study is a case report. In our case, a 50-year-old female, thought to be immunocompetent, presented with metamorphopsia and decreased visual acuity in the left eye in the setting of disseminated Nocardiosis. She had evidence of a subfoveal Nocardia lesion with subretinal fluid and CNV. Following a series of off-label injections with aflibercept, the patient had improvement in lesion size, exudation, and visual acuity. Extensive workup yielded underlying immunocompromise due to presence of anti-GM-CSF antibodies, likely predisposing her to disseminated Nocardiosis. The use of aflibercept in Nocardia chorioretinitis led to resolution of neovascular activity with visual recovery in a patient with disseminated Nocardiosis.

Choroidal neovascularization in children: etiology, clinical characteristics and treatment outcomes

PurposeTo provide data on the most frequent causes, main characteristics, management, and outcomes of pediatric choroidal neovascularization (CNV) in a major tertiary referral hospital for children, together with a review of the current literature. MethodsCase series including children diagnosed with CNV between 2008 and 2023. Age, sex, date of diagnosis, CNV etiology, CNV localization, treatment with anti-vascular endothelial growth factor (VEGF), and ophthalmological examination data at diagnosis and after one year of follow-up were recorded. Results42 eyes (31 patients) were included. Best’s disease (35.5%) was the most frequent etiology, followed by intraocular inflammation (25.8%). Most neovascular membranes (78.6%) were located within 1 disc diameter of the fovea centre. 78.6% of eyes received anti-VEGF treatment. Mean visual acuity (VA) significantly improved from logMAR 0.57 to 0.31 after one year of follow-up. ConclusionCNV in children is a serious condition with severe ophthalmological consequences. Although certain patients may spontaneously improve or maintain good VA without treatment, in many others anti-VEGF treatment may lead to significant visual improvement. VA impairment, signs of exudative CNV on OCT images and the location of CNV seem to be the most important features in the decision to treat or not to treat these patients.