Table 12.
Summary of all Systemic Adverse Events through 56-Week Visit of Follow-up*
| Sham +Focal/Grid/PRP Laser | Ranibizumab+ Focal/Grid/PRP Laser | Triamcinolone +Focal/Grid/PRP Laser | Ranibizumab/Sham** | Triamcinolone/Sham** | |
|---|---|---|---|---|---|
|
| |||||
| Total Number of Events | N = 128 | N = 178 | N = 168 | N = 44 | N = 39 |
| Blood and lymphatic system disorders | |||||
| Anaemia | 4 | 1 | 5 | 0 | 1 |
| Anaemia of chronic disease | 0 | 1 | 0 | 0 | 0 |
| Lymphadenopathy | 1 | 0 | 0 | 0 | 0 |
| Lymphoedema | 1 | 0 | 0 | 0 | 0 |
| Lymphoma | 1 | 0 | 0 | 0 | 0 |
| Cardiac disorders | |||||
| Angina pectoris | 0 | 1 | 1 | 0 | 0 |
| Arteriosclerosis coronary artery | 1 | 1 | 0 | 0 | 0 |
| Atrial flutter | 0 | 1 | 0 | 0 | 0 |
| Cardiac failure | 2 | 0 | 0 | 0 | 0 |
| Cardiac failure congestive | 1 | 6 | 3 | 0 | 1 |
| Cardiomegaly | 0 | 0 | 0 | 1 | 0 |
| Chest discomfort | 1 | 0 | 0 | 0 | 0 |
| Coronary artery disease | 0 | 1 | 2 | 0 | 0 |
| Coronary artery occlusion | 1 | 0 | 0 | 0 | 0 |
| Ischaemic cardiomyopathy | 0 | 1 | 0 | 0 | 0 |
| Myocardial infarction | 1 | 4 | 0 | 0 | 0 |
| Palpitations | 0 | 0 | 1 | 0 | 0 |
| Tachycardia | 1 | 0 | 0 | 0 | 1 |
| Ear and labyrinth disorders | |||||
| Ear pain | 0 | 1 | 0 | 0 | 0 |
| Otitis externa | 0 | 0 | 0 | 0 | 1 |
| Endocrine disorders | |||||
| Diabetes mellitus | 0 | 0 | 2 | 1 | 0 |
| Diabetes mellitus inadequate control | 0 | 1 | 1 | 0 | 0 |
| Diabetic gastroparesis | 1 | 1 | 2 | 0 | 0 |
| Diabetic ulcer | 1 | 0 | 0 | 0 | 0 |
| Hyperglycaemia | 1 | 2 | 0 | 0 | 0 |
| Hyperthyroidism | 0 | 0 | 0 | 0 | 1 |
| Hypoglycaemia | 2 | 3 | 1 | 0 | 0 |
| Hypothyroidism | 0 | 2 | 1 | 0 | 0 |
| Gastrointestinal disorders | |||||
| Abdominal pain | 0 | 0 | 4 | 0 | 0 |
| Abdominal pain upper | 0 | 0 | 2 | 0 | 0 |
| Appendiceal abscess | 1 | 0 | 0 | 0 | 0 |
| Appendicitis | 2 | 0 | 0 | 0 | 0 |
| Constipation | 0 | 0 | 3 | 0 | 0 |
| Diarrhoea | 1 | 1 | 0 | 3 | 0 |
| Diverticulum | 0 | 0 | 2 | 0 | 0 |
| Dysgeusia | 0 | 0 | 1 | 0 | 0 |
| Dyspepsia | 0 | 1 | 0 | 0 | 1 |
| Dysphagia | 0 | 0 | 1 | 0 | 0 |
| Faecaloma | 0 | 1 | 0 | 0 | 0 |
| Gastrooesophageal reflux disease | 1 | 2 | 2 | 0 | 1 |
| Impaired gastric emptying | 1 | 0 | 0 | 0 | 0 |
| Intestinal obstruction | 1 | 0 | 0 | 0 | 0 |
| Nausea | 4 | 4 | 6 | 0 | 1 |
| Oesophageal varices haemorrhage | 0 | 0 | 0 | 1 | 0 |
| Pancreatitis | 0 | 0 | 1 | 0 | 0 |
| Peptic ulcer | 0 | 0 | 1 | 0 | 0 |
| Rectal haemorrhage | 0 | 1 | 0 | 0 | 0 |
| Tooth infection | 0 | 0 | 1 | 0 | 0 |
| Vomiting | 1 | 1 | 5 | 0 | 0 |
| General disorders and administration site conditions | |||||
| Chest pain | 0 | 7 | 0 | 0 | 3 |
| Cyst | 2 | 0 | 0 | 0 | 0 |
| Death | 3 | 2 | 1 | 0 | 0 |
| Hernia | 0 | 0 | 2 | 0 | 0 |
| Oedema peripheral | 0 | 1 | 1 | 0 | 1 |
| Pyrexia | 1 | 0 | 1 | 0 | 1 |
| Swelling | 0 | 1 | 0 | 0 | 0 |
| Hepatobiliary disorders | |||||
| Cholelithiasis | 0 | 0 | 1 | 0 | 0 |
| Immune system disorders | |||||
| Asthma | 0 | 0 | 0 | 1 | 0 |
| Drug hypersensitivity | 0 | 1 | 0 | 0 | 0 |
| Hypersensitivity | 0 | 1 | 0 | 0 | 0 |
| Seasonal allergy | 1 | 0 | 1 | 0 | 0 |
| Infections and infestations | |||||
| Bronchitis | 0 | 1 | 1 | 0 | 1 |
| Bronchopneumonia | 0 | 0 | 1 | 0 | 0 |
| Candidiasis | 1 | 0 | 0 | 0 | 0 |
| Cystitis | 1 | 0 | 0 | 0 | 0 |
| Gangrene | 0 | 0 | 0 | 1 | 0 |
| Gastroenteritis | 0 | 1 | 2 | 0 | 0 |
| Gastroenteritis viral | 2 | 1 | 0 | 0 | 0 |
| Infection | 2 | 0 | 1 | 0 | 0 |
| Influenza | 1 | 3 | 1 | 0 | 1 |
| Localised infection | 3 | 2 | 4 | 0 | 1 |
| Onychomycosis | 0 | 0 | 1 | 0 | 0 |
| Osteomyelitis | 1 | 1 | 1 | 0 | 0 |
| Pharyngitis | 1 | 0 | 0 | 0 | 0 |
| Pneumonia | 1 | 4 | 3 | 0 | 1 |
| Respiratory tract infection | 1 | 0 | 0 | 0 | 0 |
| Sepsis | 0 | 0 | 0 | 0 | 1 |
| Sinusitis | 1 | 1 | 2 | 0 | 1 |
| Skin bacterial infection | 0 | 0 | 0 | 1 | 0 |
| Skin infection | 1 | 0 | 1 | 2 | 0 |
| Streptococcal infection | 0 | 0 | 0 | 0 | 1 |
| Tinea pedis | 0 | 1 | 0 | 0 | 0 |
| Upper respiratory tract infection | 2 | 0 | 4 | 1 | 2 |
| Urinary tract infection | 3 | 1 | 1 | 2 | 1 |
| Injury, poisoning and procedural complications | |||||
| Animal bite | 0 | 1 | 0 | 0 | 0 |
| Burns second degree | 0 | 1 | 0 | 0 | 0 |
| Fall | 3 | 0 | 3 | 0 | 0 |
| Fibula fracture | 0 | 0 | 0 | 1 | 0 |
| Foot fracture | 0 | 2 | 2 | 0 | 0 |
| Head injury | 0 | 0 | 1 | 0 | 0 |
| Hip fracture | 1 | 0 | 0 | 0 | 0 |
| Injury | 1 | 0 | 0 | 0 | 0 |
| Joint injury | 1 | 0 | 0 | 0 | 0 |
| Laceration | 1 | 0 | 0 | 0 | 0 |
| Limb injury | 1 | 2 | 0 | 0 | 0 |
| Road traffic accident | 0 | 0 | 0 | 0 | 1 |
| Subdural haematoma | 0 | 0 | 0 | 1 | 0 |
| Thermal burn | 0 | 2 | 1 | 0 | 0 |
| Upper limb fracture | 0 | 0 | 1 | 0 | 0 |
| Wrist fracture | 0 | 0 | 1 | 0 | 0 |
| Investigations | |||||
| Blood glucose decreased | 1 | 0 | 0 | 0 | 0 |
| Blood potassium increased | 0 | 1 | 0 | 0 | 0 |
| Heart rate decreased | 0 | 1 | 0 | 0 | 0 |
| Oxygen saturation decreased | 0 | 1 | 0 | 0 | 0 |
| Metabolism and nutrition disorders | |||||
| Dehydration | 0 | 1 | 1 | 0 | 0 |
| Diabetes mellitus inadequate control | 1 | 1 | 3 | 0 | 0 |
| Dyslipidaemia | 1 | 1 | 1 | 2 | 0 |
| Fluid overload | 1 | 0 | 1 | 0 | 0 |
| Fluid retention | 0 | 0 | 0 | 1 | 0 |
| Hypercholesterolaemia | 3 | 5 | 3 | 1 | 0 |
| Hyperkalaemia | 2 | 2 | 0 | 0 | 0 |
| Hyperlipidaemia | 0 | 1 | 1 | 0 | 0 |
| Hypocalcaemia | 1 | 0 | 0 | 0 | 0 |
| Hypokalaemia | 0 | 0 | 0 | 1 | 0 |
| Hypomagnesaemia | 0 | 1 | 0 | 0 | 0 |
| Hyponatraemia | 0 | 1 | 0 | 0 | 0 |
| Vitamin D deficiency | 0 | 0 | 1 | 0 | 1 |
| Musculoskeletal and connective tissue disorders | |||||
| Arthralgia | 1 | 2 | 0 | 1 | 0 |
| Back pain | 1 | 1 | 1 | 1 | 0 |
| Hand fracture | 0 | 0 | 1 | 0 | 0 |
| Joint sprain | 0 | 0 | 1 | 0 | 0 |
| Multiple fractures | 0 | 0 | 1 | 0 | 0 |
| Muscle spasms | 0 | 0 | 3 | 0 | 0 |
| Musculoskeletal pain | 0 | 0 | 1 | 0 | 0 |
| Myalgia | 2 | 0 | 0 | 0 | 0 |
| Neck pain | 0 | 0 | 1 | 0 | 0 |
| Osteoarthritis | 0 | 0 | 0 | 1 | 0 |
| Pain in extremity | 0 | 0 | 3 | 0 | 1 |
| Pelvic fracture | 0 | 1 | 0 | 0 | 0 |
| Periarthritis | 1 | 0 | 0 | 0 | 0 |
| Rheumatoid arthritis | 0 | 0 | 1 | 0 | 0 |
| Rib fracture | 1 | 0 | 0 | 0 | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | |||||
| Bladder cancer | 0 | 1 | 0 | 0 | 0 |
| Meningioma | 0 | 1 | 0 | 0 | 0 |
| Skin cancer | 0 | 1 | 1 | 0 | 0 |
| Nervous system disorders | |||||
| Carotid artery occlusion | 0 | 0 | 0 | 0 | 1 |
| Carpal tunnel syndrome | 1 | 1 | 0 | 0 | 0 |
| Cerebrovascular accident | 1 | 3 | 2 | 0 | 1 |
| Convulsion | 0 | 1 | 1 | 0 | 0 |
| Dysarthria | 0 | 1 | 0 | 0 | 0 |
| Facial palsy | 0 | 1 | 0 | 0 | 0 |
| Headache | 6 | 9 | 4 | 6 | 3 |
| Hypoaesthesia oral | 0 | 0 | 1 | 0 | 0 |
| Insomnia | 0 | 1 | 0 | 2 | 0 |
| Ischaemic stroke | 0 | 0 | 1 | 0 | 0 |
| Neuropathy peripheral | 0 | 1 | 0 | 0 | 0 |
| Restless legs syndrome | 0 | 0 | 1 | 0 | 0 |
| Somnolence | 0 | 0 | 1 | 0 | 0 |
| Syncope | 0 | 1 | 0 | 0 | 0 |
| Syncope vasovagal | 0 | 0 | 1 | 2 | 0 |
| Tinnitus | 0 | 0 | 1 | 0 | 0 |
| Tremor | 0 | 2 | 0 | 0 | 0 |
| Vertigo | 0 | 1 | 0 | 0 | 0 |
| Psychiatric disorders | |||||
| Anxiety | 2 | 4 | 0 | 0 | 1 |
| Depression | 2 | 4 | 1 | 1 | 0 |
| Hallucination | 0 | 1 | 0 | 0 | 0 |
| Insomnia | 0 | 0 | 1 | 0 | 0 |
| Mental disorder | 0 | 1 | 0 | 0 | 0 |
| Renal and urinary disorders | |||||
| Haematuria | 1 | 0 | 2 | 0 | 0 |
| Nephropathy | 1 | 0 | 0 | 0 | 0 |
| Neurogenic bladder | 1 | 0 | 0 | 0 | 0 |
| Obstructive uropathy | 0 | 1 | 0 | 0 | 0 |
| Pelvic pain | 1 | 0 | 0 | 0 | 0 |
| Renal disorder | 0 | 0 | 1 | 0 | 0 |
| Renal failure | 2 | 4 | 2 | 0 | 0 |
| Renal failure acute | 2 | 1 | 0 | 0 | 0 |
| Renal failure chronic | 2 | 1 | 0 | 0 | 0 |
| Renal impairment | 3 | 0 | 3 | 0 | 0 |
| Reproductive system and breast disorders | |||||
| Epididymitis | 1 | 0 | 0 | 0 | 0 |
| Erectile dysfunction | 0 | 0 | 1 | 0 | 0 |
| Prostatitis | 1 | 0 | 0 | 0 | 0 |
| Prostatomegaly | 1 | 1 | 0 | 0 | 0 |
| Testicular pain | 1 | 0 | 0 | 0 | 0 |
| Testicular swelling | 0 | 0 | 1 | 0 | 0 |
| Respiratory, thoracic and mediastinal disorders | |||||
| Acute respiratory failure | 0 | 1 | 0 | 0 | 0 |
| Asthma | 0 | 1 | 0 | 0 | 0 |
| Cough | 0 | 3 | 0 | 1 | 0 |
| Dyspnoea | 0 | 4 | 2 | 0 | 0 |
| Lung neoplasm | 0 | 0 | 2 | 0 | 0 |
| Nasopharyngitis | 2 | 6 | 6 | 2 | 0 |
| Oropharyngeal pain | 0 | 0 | 0 | 1 | 0 |
| Pharyngolaryngeal pain | 0 | 2 | 0 | 0 | 0 |
| Pleural effusion | 1 | 2 | 0 | 0 | 0 |
| Pulmonary fibrosis | 0 | 0 | 0 | 1 | 0 |
| Pulmonary oedema | 0 | 3 | 0 | 0 | 0 |
| Respiratory distress | 0 | 2 | 0 | 0 | 0 |
| Respiratory tract congestion | 0 | 1 | 0 | 0 | 0 |
| Rhinitis allergic | 1 | 0 | 0 | 1 | 1 |
| Rhinorrhoea | 1 | 1 | 0 | 0 | 0 |
| Sinusitis | 0 | 0 | 3 | 0 | 1 |
| Skin and subcutaneous tissue disorders | |||||
| Cellulitis | 1 | 1 | 1 | 0 | 0 |
| Folliculitis | 1 | 0 | 0 | 0 | 0 |
| Hyperhidrosis | 0 | 1 | 0 | 0 | 0 |
| Skin lesion | 0 | 0 | 1 | 0 | 0 |
| Skin nodule | 1 | 0 | 0 | 0 | 0 |
| Skin ulcer | 0 | 1 | 2 | 1 | 1 |
| Surgical and medical procedures | |||||
| Benign tumour excision | 0 | 0 | 1 | 0 | 0 |
| Cholecystectomy | 0 | 1 | 0 | 0 | 0 |
| Coronary arterial stent insertion | 0 | 1 | 1 | 0 | 0 |
| Stent placement | 0 | 0 | 0 | 0 | 1 |
| Surgery | 0 | 0 | 1 | 0 | 0 |
| Toe amputation | 0 | 0 | 1 | 0 | 0 |
| Uterine dilation and curettage | 1 | 0 | 0 | 0 | 0 |
| Vascular disorders | |||||
| Arteriovenous fistula | 1 | 0 | 0 | 0 | 0 |
| Hypertension | 5 | 7 | 6 | 2 | 1 |
| Iliac artery occlusion | 0 | 0 | 1 | 0 | 0 |
| Peripheral vascular disorder | 0 | 0 | 2 | 0 | 0 |
| Thrombosis | 0 | 0 | 1 | 0 | 0 |
| Transient ischaemic attack | 0 | 2 | 0 | 0 | 2 |
PRP= Panretinal photocoagulation
*
Comprehensive list of all systemic adverse events as reported by the site using the Medical Dictionary for Regulatory Activities coding.
**
Study participants with 2 study eyes.