Avastin

All eligible eyes with treatment‐naïve CSDME and good vision at baseline visit (as defined above) from 1 January 2010 to 31 March 2018 were considered for the study, thereby allowing at least 24 months of observation after the initial management decision. The 24‐month end‐point was considered to be the closest visit to 730 days of follow‐up ±30 days. Eligible eyes that received any intravitreal treatment, such as vascular endothelial growth factor (VEGF) inhibitors (ranibizumab [0.5mg Lucentis, Genentech Inc/Novartis], aflibercept [2mg Eylea, Bayer] or bevacizumab [1.25mg Avastin, Genentech Inc/Roche]) or steroid implant (dexamethasone [700µg Ozurdex intravitreal implant, Allergan) and/or macular laser photocoagulation at the baseline visit were defined as “initially treated eyes”. Initially observed eyes were defined as eligible eyes initially observed (i.e. no treatment received) for at least 4 months. There were no randomization for the management allocation and no specific management protocols, so the decision to treat or observe at baseline or during the follow‐up was determined by the physician based on symptoms, VA and OCT at the discretion of the physician in consultation with the patient, thereby reflecting routine clinical practice.

We performed a single center retrospective cohort analysis of all patients with multi-vessel PVS (gradient ≥ 4 mmHg by echocardiography or catheterization) and disease recurrence who received imatinib mesylate (Gleevec®, Novartis Inc., Basel, Switzerland) drug therapy from March 2009 to November 2019 as a part of a multimodal treatment plan. Patients who received bevacizumab (Avastin®, Genentech Inc., South San Francisco, CA, USA) in addition to imatinib mesylate at the start of therapy were also included. Patients were identified using our institutional PVS database and included those who participated in our prospective study [9 (link)] and those treated after the trial stopped enrollment. There have been no substantive changes to our therapeutic protocol for patients with PVS since the conclusion of the trial. Patients were categorized as either having single ventricle or 2-ventricle physiology at start of imatinib mesylate therapy. Patients who underwent a bi-ventricular conversion procedure prior to initiation of therapy were included in the 2-ventricle group. Only patients who had longitudinal follow-up at Boston Children’s Hospital were included. This study was approved by the Boston Children’s Hospital Institutional Review Board and was performed in accordance with the Declaration of Helsinki.

Human hepatocellular carcinoma cell line HUH-7 was purchased from Vacsera (Giza, Egypt), sorafenib p- Toluenesulfonate salt was purchased from LC Laboratories (Woburn, MA, United States), Avastin^® (bevacizumab, Genentech, United States) was purchased, in its formulated commercial preparation, from a community Pharmacy (Cairo, Egypt) and fucoidan extracted from Laminaria Japonica was purchased as a crude extract from Buchem BV (Holland). Dulbecco’s modified Eagle’s medium (DMEM) medium and fetal bovine serum (FBS) were purchased from Gibco^®, Thermo Fisher Scientific, United States. Antibiotic-antimycotic mixture (100 U/ml of penicillin, 0.1 U/ml streptomycin and 0.25 μg/ml of Amphotericin B) was purchased from Lonza^®, Walkersville, MD, United States. All other chemicals were purchased from Sigma Aldrich, United States unless otherwise specified.

Macular edema was defined as a CMT ≥ 300 μm based on the ETDRS protocol, which involved segmentation of the macula into a central circle, inner ring, and outer ring of 1-, 3-, and 6-mm diameters. The CMT was measured by calculating the average retinal thickness in a circle of 1 mm diameter centered on the fovea, and measuring the distance between the first signal from the vitreoretinal interface and the outer border of the retinal pigment epithelium. Recurrence of ME was defined as the reappearance of ME in eyes with previously resolved ME (CMT < 300 μm).
Macular edema was treated with as-needed intravitreal injections of anti-VEGF agents, bevacizumab (1.25 mg; Avastin, Genentech, San Francisco, CA, USA) or ranibizumab (Lucentis, 0.5 mg; Genentech, Inc., San Francisco, CA, USA). If three consecutive monthly anti-VEGF injections failed to resolve ME, the patient was switched to intravitreal dexamethasone implant or triamcinolone acetonide injections.