Table 1

Summary of included randomised controlled studies

Study identifier,
study location
Description of study populationNumber of patients (eyes)Interventions (treatment schedule and numbers treated)Comparators (treatment schedule and numbers treated)Reported safety outcomesInformation relating to preparation of intravitreal bevacizumab
Studies including patients with age-related macular degeneration (n=7 studies)
Bashshur et al,14
Lebanon
Neovascular age-related macular degeneration
BCVA, 20/50 to 20/200
Submacular scarring or haemorrhage, sparing the fovea
Mean age, 74.5 years
62 (NR)IVB: 2.5 mg, mean 2.4 injections (n=32)Laser therapy: mean 2.3 sessions (n=30)Systemic adverse events
Hypertension
Outcomes at 6 months
IVB prepared in hospital pharmacy
Biswas et al,15 IndiaChoroidal neovascularisation secondary to age-related macular degeneration
BCVA, 35 to 70 ETDRS letter
CMT, >250μm
Mean age, not reported
60 (60)IVB: 1.25 mg, 3 monthly injections, mean 4.3 (n=30)IVR: 0.5 mg, 3 monthly injections, mean 5.6 (n=30)Significant adverse events (unspecified)
Outcome at 18 months
Methods of IVB preparation not reported
CATT 2012,16 USAChoroidal neovascularisation secondary to age-related macular degeneration
BCVA, 20/25 to 20/320
Mean age, 79.5 years
1185 (1107)IVB: 1.25 mg, monthly or as needed (n=586)IVR: 0.5 mg, monthly or as needed (n=599)Death
Endophthalmitis
Hypertension
Adverse events associated with anti-VEGF treatment
Arteriothrombotic adverse events
Outcomes at 2 years
Re-packaging of commercially available bevacizumab into glass vials in an aseptic facility
IVAN 2012,19 UKNeovascular age-related macular degeneration;
BCVA, ≥25 ETDRS letters
Mean age, 77.0 years
610IVB, 1.25 mg as continuous or as needed treatment at 3 separate visits (n=296)IVR, 0.5 mg as continuous or as needed treatment at 3 separate visits (n=314 eyes)Serious adverse events
Death
Arteriothrombotic events
Transient ischaemic attack
Hospitalised for angina
Outcomes at 1 year
Commercially repackaged and prefilled syringes IVB
Lazic and Gabric,20 CroatiaMinimally classic or occult choroidal neovascularisation secondary to age-related macular degeneration
BCVA, ≥20/400
Mean age, 75.7 years
165 (165)IVB, 1.25 mg (n=55)1. Laser therapy: according to recommended standard procedures (n=55)
2. Combination treatment, that is, laser therapy followed by IVB, 1.25 mg within an hour (n=55)
Pigment epithelial tears
Posterior vitreous detachment
Thromboembolic events
Cataract progression
Outcomes at 3 months
Methods of IVB preparation not reported
Schimid-Kubista et al,24 AustriaChoroidal neovascularisation secondary to neovascular age-related macular degeneration
BCVA, 5 to 40 ETDRS letters
Mean age, 77.5 years
48 (48)IVB, 1.0 mg every 6 weeks; total of 3 injections (n=13)1. IVP, 0.3 mg every 6 weeks; total of 3 injections (n=18)
2. IVB, 1.0 mg then two injections of IVP 0.3 mg 6 weeks apart (n=17)
IOP
Raised blood pressure
Outcomes at 6 months
Methods of IVB preparation not reported
Tufail et al,26 UKNeovascular age-related macular degeneration;
BCVA, 6/12 to 6/96 (Snellen
equivalent) or 25 to 70 ETDRS letter scores
Mean age, 81 years
131 (NR)IVB, 1.25 mg, three loading injections at 6 week intervals followed by further treatment if required at 6 week intervals, mean injections 7.1 (n=65).

1. Laser therapy, (n=16)
2. IVP, 0.3 mg, (n=38)
3. Sham injection, (n=12)
Endophthalmitis
Uveitis
Retinal detachment
Retinal tear
Vitreous haemorrhage
Lens damage
Myocardial infarction
Stroke
Cerebral infarction
Death
Outcomes at 1 year
IVB injections were prepared as single use syringes with a shelf life of 6 weeks. Syringes were placed in sealed plastic pouches
Studies including patients with diabetic macular oedema (n=8 studies)
Ahmadieh et al,7 IranDiabetic macular oedema
BCVA,≤20/40
Mean age, 59.7 years
101 (115)IVB, 1.25 mg at baseline and weeks 6 and 12 (n=41 eyes)1. IVB, 1.25 mg and IVT, 2 mg at baseline, then IVB, 1.25 mg at weeks 6 and 12 (n=37 eyes)
2. Sham injection (n=37 eyes)
Death
Marked anterior chamber reaction
Progression of fibrous proliferation
Outcomes at 24 weeks
Methods of IVB preparation not reported
DRCRN 2007,10 USADiabetic macular oedema (patients with type 1 and type 2 diabetes)
BCVA, ETDRS VA letter score, 24 to78 (20/32 to 20/320)
CMT ≥275 μm
Median age, 65 years
109 (109)1. IVB, 1.25 mg at baseline
and week 6
(n=22 eyes)
2. IVB, 2.5 mg at baseline, week 6 (n=24 eyes)
1. Laser treatment at baseline (n=19 eyes)
2. IVB, 1.25 mg at baseline, laser treatment at week 3, then IVB, 1.25 mg at week 6 (n=22 eyes)
3. IVB, 1.25 mg at baseline, sham at week 6 (n=22 eyes)
Endophthalmitis, raised intraocular pressure, raised blood pressure, myocardial infarction, congestive heart failure
Outcomes over a 70-week period
Methods of IVB preparation not reported
Faghihi et al,11 IranDiabetic macular oedema (patients with type 2 diabetes)
BCVA, ≤20/40
CMT, >250μm
Mean age, 57.5 years
110 (130)IVB, 1.25 mg, dosing schedule not reported (n = 42 eyes)1. Laser (n = 47 eyes)
2. IVB (1.25 mg) + IVT (2 mg) (n=41 eyes)
Safety assessment
Vitreous haemorrhage
Ocular hypertension (≥23 mm Hg)
Outcome 16 weeks
Methods of IVB preparation not reported
Lim et al,21 KoreaDiabetic macular oedema
BCVA, not reported
CMT ≥300 µm
Mean age, 60.0 years
111 (120)IVB, 1.25 mg at baseline and at week 6 (n=36)1. IVT, 2 mg (n=38)
2. IVB (1.25 mg)+IVT (2 mg) (n=37)
Hypertension
Thromboembolic AE
Serious ocular complications
IOP
Outcomes at 1 year
Methods of IVB preparation not reported
Marey and Ellakwa,22 EgyptClinically significant diabetic macular oedema
BCVA, not reported
CMT at baseline, reported per study groups
Mean age, 57.7 years
90 (90)IVB, 1.25 mg (n=30)1. IVT, 4 mg (n=30)
2. IVB (1.25 mg)+IVT (4 mg) (n=30)
IOP>22 mm Hg
Cataracts
Outcomes at 12 weeks
Methods of IVB preparation not reported
Michaelides et al,9 UKClinically significant diabetic macular oedema (in patients with type 1 or type 2 diabetes)
BCVA, 35 to 69 ETDRS letters
CMT ≥279µm
Mean age, 64.2 years
80 (80)


IVB, 1.25 mg at baseline, and then every 6 weeks as needed; number of injections ranged between 3 and 9 (n=42)Laser therapy, every 4 months as needed; number of treatments, ranged between 1 and 4 (n=38)Death
IOP
Loss of 30 ETDRS letters
Vitreous haemorrhage
Cerebrovascular accident
Outcomes at 12 months
IVB prepared by Moorfields, London
Shahin et al,25 EgyptDiffuse diabetic macular oedema
BCVA, not reported
CMT ≥292µm
Mean age, 52.7 years
32 (48)IVB, 1.25 mg, single injection (n=24 eyes)IVT, 4 mg, single injection (n=24 eyes)IOP (≥23–43 mm Hg)
Visually significant cataract
Outcomes at 3 months
Methods of IVB preparation not reported
Soheilian et al,2 IranDiabetic macular oedema
BCVA, 20/40 to 20/300
CMT, not used as inclusion criterion
Mean age, 60.5 years
129 (150)IVB, 1.25 mg at baseline; treated repeated at 3 monthly interval on an as-needed basis (n=50 eyes)1. IVB, 1.25 mg+IVT, 2 mg; treated repeated at 3 monthly interval on an as-needed basis (n=50 eyes)
2. Laser therapy; treated repeated at 3 monthly interval on an as-needed basis (n=50 eyes)
Death
Lens opacities
IOP
Vitreous haemorrhage
High risk proliferative diabetic retinopathy
Outcomes at 2 years

Methods of IVB preparation not reported
Studies including patients with retinal vein occlusion (n=4 studies)
Cekic et al,8 TurkeyMacular oedema due to branch retinal vein occlusion
BCVA, ≤20/40
CMT, >250 μm
Mean age, 63 years
21 (21)*IVB: 1.25 mg, mean 1.6 injections
(n=14)
IVT: 4 mg, mean 1.4 injections (n=17)
IVT+IVB (n=21)
Endophthalmitis, uveitis, thromboembolic events
Outcomes at 6 months
Methods of IVB preparation not reported
Ding et al,17 ChinaMacular oedema secondary to retinal vein occlusion (unspecified)
BCVA, ≤20/40
CMT, >250 μm
Mean age, 54 years
31 (32)IVB, 1.25 mg, repeat treatment given if condition persisted or recurred (n=16 eyes)IVT, 4 mg, repeat treatment given if condition persisted or recurred (n=16 eyes)IOP>21 mm Hg
Outcomes at 9 months
Methods of IVB preparation not reported
Epstein et al,12 SwedenMacular oedema secondary to central retinal vein occlusion
BCVA, 15 to 65 ETDRS letters (approx. 20/50 to 20/500)
CMT ≥ 300μm
60 (60)IVB, 1.25 mg at baseline and at weeks 6, 12 and 18 (n =30)Sham injection: at baseline and at weeks 6, 12 and 18 (n=30)Endophthalmitis
Retinal tear
Retinal detachment
No serious non-ocular adverse events
Outcomes at 6 months
IVB prepared in hospital pharmacy
Moradian et al,13 IranAcute branch retinal vein occlusion
BCVA, ≤20/50
Mean age, 57.6 years
81 (81)IVB, 1.25 mg at baseline and 6 weeks (n=42)Sham injection, at baseline and 6 weeks (n=39)Foveal haemorrhage
Foveal ischemia
Outcomes at 12 weeks
Methods of IVB preparation not reported
Studies including patients with other ophthalmic conditions (n=3 studies)
Gharbiya et al,18 ItalyPathologic myopia†
BCVA, ≥26 ETDRS letters
Mean age, 59.5 years
32 (32)IVB, 1.25 mg at baseline, then given as needed
(n=16 eyes)
IVR, 0.5 mg at baseline, then given as needed (n=16 eyes)Systemic adverse events
Endophthalmitis Retinal detachment
Vitreous haemorrhage
Hypertension
IOP
Outcomes at 6 months
Methods of IVB preparation not reported
Patwardhan et al,23 IndiaVitreous haemorrhage (grade 3 or 4), secondary to Earl's disease
Mean age, 25.5 years
20 (20)IVB, 1.25 mg every 4 weeks (n=10 eyes)No active treatment (n=10 eyes)Tractional retinal detachment
Outcomes at 12 weeks
Methods of IVB preparation not reported
Yazdani et al,27 IranNeovascular glaucoma
BCVA ≥20/200
Mean age, 59.5 years
26 (26)IVB, 2.5 mg; 3 injections given monthly (n=14 eyes)Sham injection; 3 injections given monthly (n=12 eyes)Hyphema
Injection related adverse events
Outcomes at 6 months
Methods of IVB preparation not reported
  • This table summarises the study characteristics of the 22 included randomised controlled studies. Data shown here include patient charateristics, interventions and outcomes reported in the included studies.

  • Calculation of mean age, when not specified, was based on the assumption that reported ages per treatment arms were normally distributed.

  • *The study population included 52 patients, of these 21 patients received a combination of intravitreal bevacizumab and intravitreal triamcinolone.

  • †This condition was defined as an axial length of at least 26.5 of subfoveal or juxtafoveal choroidal neovascularisation.

  • BCVA, best corrected visual acuity; CMT, central macular thickness; ETDRS, Early Treatment Diabetic Retinopathy Score; IOP, intraocular pressure; IVB, intravitreal bevacizumab; IVP, intravitreal pegaptinib; IVR, intravitreal ranibizumab.