cardiac significant disease arrhythmia function history impaired arrhythmias requiring uncontrolled retinal rvo occlusion vein history evidence current retinopathy serous risk significant clinically disease cardiac history uncontrolled pulmonary investigator active ecg cardiovascular significant disease clinically uncontrolled history including evidence pulmonary condition pleural ascites effusion effusions pericardial requiring paracentesis drainage clinically thoracentesis