Table 4

Bevacizumab studies

StudyParticipants and baseline valuesInterventionOutcome (change from baseline at study end)
BOLT Study (Michaelides et al/Rajendram et al))23 52 85
UK
Design: 2-arm RCT
Follow-up: 12 months
N: 80 eyes of 80 patients
Inclusion criteria: ≥18 years, type 1 or 2 DM, BCVA in the study eye 35–69 ETDRS letters at 4 m (≥6/60 or ≤6/12), center-involving clinically significant DMO with CMT ≥270 µm; media clarity, papillary dilation and cooperation sufficient for adequate fundus imaging; a least 1 prior macular laser therapy; IOP <30 mm Hg; fellow eye BCVA ≥3/60; fellow eye received no anti-VEGF in past 3 months and no expectation of such therapy
Exclusion criteria: (ocular for study eye) macular ischemia, macular oedema due to causes other than DMO, coexistent ocular disease affecting VA or DMO, any treatment for DMO in prior 3 months, PRP within 3 months prior to randomisation or anticipated, PDR, HbA1c >11%, medical history of chronic renal failure; any thromboembolic event within 6 months prior to randomisation, unstable angina, evidence of active ischemia on ECG; major surgery within 28 days of randomisation or planned; participation in an investigational drug trial; systemic anti-VEGF or pro-VEGF treatment within 3 months of enrolment; pregnancy, lactation; intraocular surgery within 3 months of randomisation; aphakia; uncontrolled glaucoma; significant external ocular disease
Age: 64.2 SD8.8 years
Sex: 31% female
Diabetes type: 90% type 2 DM, 10% type 1 DM
HbA1c: 7.5–7.6 SD1.2–1.4%
Baseline VA: ETDRS letter score 54.6–55.7 SD8.6–9.7
Baseline CMT: 481–507 SD121–145 µm
Comorbidities: 19% mild NPDR (level 35), 46% moderate NPDR (level 43), 19% moderately severe NPDR (level 47), 13% severe NPDR (level 53), 3% moderate PDR (level 65), 79–88% phakic
Group 1 (MLT, n=38 eyes): modified ETDRS macular laser therapy; reviewed every 4 months up to 52 weeks; retreatment performed if clinically indicated by ETDRS guidelines (median 4 laser treatments)
Group 2 (IVB, n=42 eyes): 1.25 mg (0.05 ml) IV bevacizumab at baseline, 6 and 12 weeks; subsequent IVB injections (up to 52 weeks) guided by an OCT-based retreatment protocol (median 13 injections)
Laser modified ETDRS protocol, retreatment by ETDRS guidelines
At 24 months
BCVA (ETDRS):
BCVA.mean (SD)p Value
MLT−0.5 (10.6)
IVB+8.6 (9.1)0.005 vs MLT
BCVA gain categories (letters)
MLTgaining ≥10: 7%
losing >15: 4%
IVBgaining ≥10: 49%
losing >15: 32%
0.001 vs MLT
0.004 vs MLT
CMT (µm, quartiles)p Value
MLT−118 SD171
IVB−146 SD1220.62 vs MLT
Lam et al35
Hong Kong
Design: 2-arm RCT
Follow-up: 6 months
N: 52 eyes of 52 patients
Inclusion criteria: ≥18 years, type 1 or 2 DM, clinically significant DMO (slit-lamp biomicroscopy, ETDRS criteria; leakage confirmed by fluorescein angiography, CMT ≥250 µm on OCT), BCVA ≥1.3 ETDRS logMAR units; only patients with diffuse DMO recruited
Exclusion criteria: macular oedema due to reasons other than diabetes, significant media opacities, macular ischemia of ≥1 disk area, vitreomacular traction, PDR, aphakia, glaucoma or ocular hypertension, previous anti-VEGF treatment, intraocular surgery except uncomplicated cataract extraction (but > 6 months prior), focal DMO, any laser procedure within previous 4 months, subtenon or intravitreal triamcinolone injection within 6 months, pregnancy
Age: 65.3 SD8.9 years
Sex: 46.2% female
Diabetes type: not reported
HbA1c: 7.5 SD1%
Baseline VA: 0.61 SD0.29 logMAR
Baseline CMT: 466 SD127 µm Comorbidities: not reported
Group 1 (IVB1.25, n=26 eyes): 1.25 mg bevacizumab (0.05 ml)
Group 2 (IVB2.5, n=26 eyes): 2.5 mg bevacizumab (0.1 ml)
Regimen for all groups: 3 monthly IV injections, topical 0.5% levofloxacin 4×/day for up to 2 weeks after each injection
At 6 months
BCVA (ETDRS chart):
BCVA (logMAR) p Value
IVB1.250.11 SD0.31 (+5.5 letters)0.018 vs baseline, NS vs IVB2.5
IVB2.50.13 SD0.26 (+6.5 letters)0.003 vs baseline
CMT (OCT)CMT (µm)p Value
IVB1.25960.002 vs baseline, NS vs IVB2.5
IVB2.5740.013 vs baseline
Subgroups:
▸ For patients with previous DMO treatment (mainly laser): no significant reduction in CMT at 6 months (452 µm at baseline to 416 µm at 6 months, p=0.22); no significant improvement in BCVA (0.66 logMAR at baseline to 0.56 logMAR at 6 months (+5 letters), p=0.074)
Faghihi et al53
Iran
Design: 2-arm RCT
Follow-up: 6 months
N: 80 eyes of 40 patients
Inclusion criteria: Bilateral non-tractional CSME, 10/10> V.A≥1/10, Controlled blood pressure.
Exclusion criteria: Advanced or advanced active PDR, significant cataract, glaucoma, history of recent vascular accident (eg, MI, CVA), Previous treatment of CSME or PDR, or pharmacotherapy for CSME, macular ischemia and uncontrolled hypertension
Age: 57.7±8 years
Sex: 27.5% females
Diabetes type: NR
HbA1c: 8.42±1.82 g/dl
Baseline VA: 0.326–0.409 (SD 0.279–0.332)
Baseline CMT: 277 um–287 um (SD 78–98)
Comorbidities: not reported
Group 1 (IVB, n=40 eyes): 1.25 mg bevacizumab
Group 2 (IVB+MPC, n=40 eyes): 1.25 mg bevacizumab
Regimen for all groups: Eyes examined every 2 months and if evidence of CSME IVB was injected. Mean of the number of IVB injections in IVB group and IVB+MPC group were 2.23±1.24 and 2.49±1.09, respectively
At 6 months
Mean change in BCVA (ETDRS chart):
 BCVA (logMAR)p Value
IVB0.138<0.05 vs baseline
IVB+MPC0.179<0.05 vs baseline
▸ no statistically significant difference between the two groups
CMT (OCT):
CMT (µm)p Value
IVB−39<0.05 vs baseline
IVB+MPC−39<0.05 vs baseline
▸ No statistically significant difference between the two groups
  • BCVA, best corrected visual acuity; C, control; CMT, central macular thickness; CSME, clinically significant macular oedema; DDS, dexamethasone; DIL, dexamethasone followed by laser; DM, diabetes mellitus; DMO, diabetic macular oedema; DP, diastolic pressure; DR, diabetic retinopathy; HR QoL, health-related quality of life; IOP, intraocular pressure; IV, intravitreal; IVB, intravitreal bevacizumab; IVP, intravitreal pegaptanib; IVR, intravitreal ranibizumab; IVT, intravitreal triamcinolone; IVTL, intravitreal triamcinolone plus laser; IVVTE, intravitreal VEGF Trap Eye; L, laser; MLT/MPC, macular laser therapy/macular photocoagulation; NEI VFQ-25, National Eye Institute Visual Function Questionnaire-25; NPDR, non-proliferative diabetic retinopathy; NR, not reported; OCT, optical coherence tomography; PDR, proliferative diabetic retinopathy; PRP, panretinal photocoagulation; RCT, randomised controlled trial; SOC, standard of care; SP, systolic pressure; SRFA, fluocinolone; VA, visual acuity; VEGF, vascular endothelia growth factor.