Table 2

Summary of included observational studies

Author (year)Study typeCondition (patients' mean age in years)Number of patients (number of eyes)Baseline comparability (yes/ no/unknown/not applicable)Dosage (mg) including frequency of dosingNumber of injections/patients (mean)Follow-upInformation on preparation of bevacizumabFundingNotes
Abraham-Marin (2007)33Case series, (prospective)CNV due to AMD (76)39 (39)NA2.5 mg14 weeksNRNR
Arevalo (2010)34Case series, (retrospective)CNV due to AMD180 (207)NA1.25 mg (59.9%)
2.5 mg (40.1%)
Frequency of dosing at discretion of treating physician
5.1 (per eye)1, 3, 6, 12 and 24 months after the initial injectionNRArevalo-Coutinho Foundation for Research in Ophthalmology, Venezuela
Artunay (2009)35Case series, (retrospective)Various* (NR)NR (1822)NA1.25 mg once or repeatedNR1–7 days, 4 weeks, 8 weeksNRNR
Azad (2008)36Non-randomised trial (prospective)subfoveal CNV due to AMD (63)40 (40)NA1.25 mg2.46 monthsNRNR
Baba (2010)37Case series (retrospective)Myopic CNV40 (40)Yes1.25 mg1.3 to 1.524 monthsNRNRTreatment groups: PDT (n=16); PDT and IVB (n=12); IVB only (n=12)
Bakri (2009)38Case series, (retrospective)Various† (NR)35 (70)NA1.25 mg5.939 daysNRThe Research To Prevent Blindness, New York
Bashshur (2009)28Nonrandomised trial, open-label, prospective (extension study)CNV due to AMD (72.2)51 (51)NA2.5 mg2.5 (3.4 during first 12 months, decreased to 1.5 during second year)24 monthslocal dispensing serviceAmerican University of Beirut Medical Center
Carneiro (2010)39Cohort, (prospective)Subfoveal or juxtafoveal CNV secondary to AMD (76.9)(80)NR1.25 mg46 months, 12 monthsNRSociedade Portuguesa de Oftalmologia, Hospitalde Sao Joao,
Carneiro (2011)40Cohort (retrospective):IVB vs IVRAMD (77.8)97 (IVB group)Yes (IVB:IVR)1.25 mg;7.82.3 yearsNRSociedade Portuguesa de Oftalmologia, Hospitalde Sao Joao, Swiss National Foundation and Walter and Gertrud Sienenthaler FoundationIncreased rate of ATEs in IVB group compared to IVT (secondary analyses
Chen (2010)41Non-randomised cohort (retrospective)MO due to BRVO (60.7)24 (25)Yes (IVB:IVT:control; n=83)2.5 mg single injection then as neededNR10 months (mean)NRNRPatients received IOP-lowering treatment during follow-up period if IOP ≥21 mm Hg.
Anterior paracentesis was performed before IVB to reduce ocular pressure.
Author's conclusion:
IVB better than IVT
Cleary (2008)42Case series (retrospective)Neovascular AMD (75)111 (112)NA1.25 mg, once then as neededNR4.9 (range 1–12)Local dispensing serviceNone
Costa (2006)43Non-randomised dose escalation study (prospective)CNV caused by AMD (74.6)45 (45)Yes (1.0 mg:1.5 mg:2.0 mg)1.0 mg, 1.5 mg and 2.0 mgNR3Local dispensing servicePublic funding (Foundation for Research Support of the State of São Paulo)Reported as a dose escalation study but difficult to tell how many doses each participant was given and how far apart
Costagliola (2009)44Case series (retrospective)CNV (subfoveal) due to AMD (73.2)68 (68)NA1.25; then monthly as per needed3.87 (first 6 months); 1.09 (for remaining 6 months)12Local dispensing serviceNRExclusion criteria included previous history of thromboembolic events; uncontrolled hypertension, BP >150/90 mm Hg.
Topical antibiotics prescribed for 3 days, after injection
Curtis (2010)45Cohort (retrospective)AMD (median, 81.0)27 962 (IVB only; n=146 942)Yes (IVB:PDT: IVP:IVR)NRNR12 monthsNRResearch agreement between OSI Eyetech and Duke UniversityPatient data were censored when at the time when a treatment which was different from initially assigned intervention was received. Between July and December 2006, study population was limited to treatment-naïve patients who received bevacizumab or ranibizumab
Falkenstein (2007)46Case series (prospective)AMD (79.4)70 (NR)NA1.25 mg assumed (0.05 mL)1.74 (calculated from 122 injections for 70 patients)3,10 and 15 minutesNRNR
Fintak (2008)47cohort (retrospective)Various (NR)12 585 (IVB injections)NR1.25 mgNR5 daysLocal dispensing serviceNRNumber of injections not reported
Fong (2008)48Case series (retrospective)AMD (82)109 (109)NA1.25 mg, three consecutive monthly injections then as neededNR9.4 months (range 6-12)Compounding pharmacyNR
Frenkel 201049Cohort (retrospective)AMD (80)47‡Unknown (IVB: ranibizumab: pegaptanib)1.25 mg120 minutesNRNRFirst injection only selected for the study
Fukami (2011)50 (abstract)Case series (retrospective)NR (NR)12 (12)NANRNR2 daysNRNR
Gamulescu (2010)51Cohort (retrospective)§AMD (77.5)30 (NR)NR1.25 mg every 4 weeks
3 initial injections
NR2-4 months after last injectionNRNR
Gomi (2008)52Case series (Retrospective)Polypoidal choroidal vasculopathy (65.4)11 (11)NA1 mg¶ once or as needed

NR9.4 months (±4.4)NRNR
Good (2011)31Cohort (retrospective)**AMD (76.6)NR (101)††Yes1.25 mg7.086.6 days meanNRNR
Goverdhan (2008)53Case series (retrospective)CNV due to AMD (79.5)53 (53)NA1.25 mg
Repeat injections offered if CNV persisted or fresh haemorrhage or subretinal fluid observed.
1.36Day 1 and after 2 week visits then at 4-week intervals.
Minimum 6 months (range 4 to 12 months)
NRNR
Gower (2011)54 (abstract)Cohort (retrospective)Neovascular AMD (NR)NR (NR)NR (IVB:IVR)NRNRNRNRNRHRs adjusted for baseline comorbidities, demographics and socio-economic status
Hernandez-Rojas (2007)55Case series (prospective)CNV due to pathological myopia (53.9)13 (13) (at follow-up—one patients lost to follow-up)NA2.5 mg/0.1 mL once or as neededNR3 monthsNRNR
Higashide (2012)56Case series (retrospective)Neovascular glaucoma (63.5)70 (84)NA1.25 mg1.43 monthsNRNR
Hollands (2007)57Case series (prospective)Neovascular AMD (84.6%); DMO (6.7%); Others—histoplasmosis (8.7%) (76)104NA1.25 mg

NR30 minNRNR
Ikuno (2009)58Case series (retrospective)CNV due to myopia (58.4)63 (63)NA1 mg2.412 monthsNRThe Ministry of Education, Culture, Sports Science and Technology of Japan;
Health and Labor Sciences Research of Japan
Re-injection considered after 2–3 months if fluorescein leakage in angiograam or subretinal fluid persisted
Inman (2011)59Case series (retrospective)NR608 (sample included patients that received IVB, IVP and IVR)NANRUnclear (1841 injections of IVB, 428 IVP and 2421 IVR)4.4 yearsLocal dispensing serviceNRThis study reported incidence of infectious endophthalmitis associated with 2% topical lidocaine gel anaesthesia. No information on conditions being treated or patient demographics.
Jaissle (2009)60Case series (prospective)MO due to BRVO (median, 68)23 (23)NA1.25 mg (re-injection considered if macular oedema persisted in foveal area and visual acuity 20/32 or worse)NR1 year. (examined every 6 weeks)NRGerman Opthalmological SocietyDuring the 1-year
follow-up, an average of 2.4 re-injections (range, 0–5) were administered, with a mean of 1.6 re-injections within the first 6 months (weeks 6–24) and a further 0.8 re-injections over the latter 6 months (weeks 30–48).
Johnson (2010)61Case series (retrospective)Various‡‡ (76.5)173 (193)NANR3.98Median follow-up; 40 days (range 19 to 170 days)NRQueen's University, Canada
Jonas (2007)62Case series (retrospective)AMD625 (684)NA1.5 mg1.95≥4 weeksLocal dispensing serviceNR534 re-injections
Jonas (2008)63Case series (retrospective, consecutive)VariousNR (3818 IVB injections)NA1.5 mgNR≥3 monthsNRNone
Julian (2011)64Case series (retrospective)CNV due to uveitis (median, 41.9)15 (15)NA1.25 mg (re-treatment based on signs of active neovascularisation)4.2517.6 (median)NRNRIn all cases, optimum control of intraocular inflammation was achieved by the time IVB was initiated
Kim (2009)32Before–after study of IVB group and triamcinolone acetonide group (retrospective)MO due to BRVO (56.9)50 (50) (22 received IVB and 28 received triamcinolone acetonide)NA1.25 mg single doseNR24 weeksNRNRNR
Kim (2011)65Case series (retrospective)DMO48 (65)Yes1.25 mgNR≥12 monthsNRGrant from Kyung Hee University
Kim (2011)29Non-randomised controlled study (prospective, consecutive)AMD, RVO, DMO (64.8)60 (60)Yes1.25 mg1NRNRNR
Kiss (2006)66case-control (retrospective)§§AMD (NR)61Yes1 mg17 daysLocal dispensing serviceNR
Krebs (2009)67Case series (prospective)AMD (NR)44 (44)Unknown1.25 mg 3 monthly injections based on OCT and FA findings2.61 week, 1 month and 3 monthsNRL. Boltzmann Institute

Kriechbaum (2008)68Case series (prospective)MO due to BRVO or CRVO (66)28 (29)Unknown1 mg at 4-week intervals 3 intravitreal injections5.31, 7 and 28 monthsLocal dispensing serviceNR
Krishnan (2009)69Case control (retrospective) ¶¶CNV due to AMD (80.5)14No1.25 mgNR2 and 4 weeksNRNR
Kumar (2012)70Case series (retrospective)Eales’ disease (median, 33)14 (14)Unknown1.25 mg13 monthsNRNR
Lazic (2007)71Case series (prospective)CNV secondary to AMD102 (102)NA1.25 mg, once then as neededNR≥1.5 monthsNRNoneFollow-up was 6-weekly and ongoing
Lima (2009)72Retrospective cohort studyVarious, mostly AMD 326 (IVB injections)NRNRNRNRNRMacula Foundation Inc.Same-day bilateral injections
Lommatzsch (2009)73Case series (retrospective)AMD (77.7)86NR1.25 mg at 6 week intervalsNR42.4 weeksNRNR
Lorenz (2010)74Case series (retrospective)Various***144 (145)Yes1.25 mg1.6314local dispensing serviceNone
Mason (2008)75Case series (retrospective)Various†††NRNR1.25 mgNRNRNRUniversity research grant, New York.
Manayath (2009)76Case series (prospective)CMO due to CRVO
15 (64)
15No1.25 mg2.26-18 monthsNRNR
Rasier (2009)77Quasi-experimental ‡‡‡AMD (67.2)82Unknown1.25 mg16 weeksNRNR
Russo (2009)78Non-randomised controlled trialMO due to BRVO15 (15)Yes (IVB:LGP)1.25 mg, once or repeated as necessaryNR12 monthsNRNRNo. of eyes/patients refers to IVB group
Saeed (2011)79Cohort (prospective)Retinal vascular occlusions and other causes of CMO (68.6)18NA1.25 mgNRNRNRNRAuthors reported that nti-VEGF related reflux was not associated with a sub-therapeutic effect
Shah (2011)80Cohort (retrospective)Various10 958 (IVB injections)NRNRNR6 daysNRNR
Sharma (2012)81Cohort (retrospective)AMD, DMO RVO (IVB group,76.9)173 (693 IVB injections)No difference in age and VA (IVB:IVR)1 mgunclearNRLocal dispensing servicePart-funded by Novartis (and part-funded by Canadian Institutes for Health Research)IVR patients were on average 1.8 years
older than IVB patients (78.7 vs 76.9, p
0.01) and had slightly worse baseline vision (6/76
vs 6/64, p 0.013). 195 out of the 351 patients that received IVR, had been treated previously with IVB (mean, 4.3 injections per patient). Prior treatment in IVB group unclear
Shienbaum (2012)82Case series (retrospective)AMD73 (74)Yes (IVB:IVR)NR (Monthly treatment until no intraretinal or subretinal fluid on optical coherence tomography. Treatment intervals determined by signs of exudationNR1.41 yearsNRNone reported
Shima (2008)83Case series (retrospective)Various§§§707 (1300 injections)NR1 mg
Once or repeated injections
NR≥2 monthsNRHealth
Sciences Research Grant, Ministry of Health, Labour and Welfare, Japan
Shimada (2011)84Case series (retrospective)Myopic CNV (58.4)74 (74)NA1.25 mg
At baseline, week 1, then monthly (unspecified length of time)
NR12 months (SD-4.3)NRGrants 19390441 and 19659445 from the Japan Society for the Promotion of Science, Tokyo, Japan
Sivkova (2010)85case series (prospective)CME due to DR, BRVO and CRVO (DR patients 59.7;
RVO patients, 68)
96 (107)Unclear (DR:RVO)1.25 mg 3 consecutive injections at 1-monthly intervalsNR4 monthsNRNRNo significant difference in adverse events between groups
Sohn (2011)86Case control (prospective) ¶¶¶DMO (54.5)11NA1.25 mgNR1.3 monthsNRGachonUniveristy, Incheon Korea
Song (2011)87Case control (retrospective)****DMO (57.1)35 (58)Yes (IVB:IVT)1.25 mgNR8 weeksNRInstitute for Medicine research grant of Kosin University College of Medicine
Sonmez (2011)88Case series (prospective)Subfoveal CMO due to AMD (69.4)24 (24)NA1.25 mg weeks 0, 6 and 12, then every 12 weeks until week 485NRNRNROf 27 patients, 3 were lost to follow-up/protocol violation)
Spandau (2006)89Case series (retrospective, consecutive)AMD63NA1.5 mgNR≥2 monthsNRNR
Torres-Soriano (2012)90Case series (prospective)CNV PDR, RVO (NR)31NA2.5 mg, frequency not reported1.31 monthNRNR
Valmaggia (2009)91Case series (retrospective)CNV due to AMD (75.5)324NA1.25 mg; then every 6 weeks. Frequency not reported3.3NRLocal pharmacyNR
Weinberger (2007)92Case series (retrospective)PED in exudative AMD (76)31 (31)NA1.25 mg onceNR1–7 monthsNRAcademic institution
Wickremasinghe (2008)93Case series (retrospective)Neovascular AMD1278 IVB injectionsNA1.25 mgNR1 weekNRNR
Wu (2008)94interventional case series (prospective)Various (including RVO, DMO)1173 (1310)NA 1.25 mg (16%), 2.5 mg (89%)3.7 (3.3 per eye)12–15 (13.6)NRNo
Yoon (2012)95Case series (retrospective)Myopic CNV (49)26NA1.25 mg2.212 monthsNRNROf the 40 patients included in the study, 14 received IVR
Zhang (2012)96Non-randomised interventional case series (prospective)Subfoveal idiopathic CNV (32)40NA1.25 mg212 monthsNRNR
  • This table summarises the study characteristics of included observational studies.Data shown here include patient charateristics, interventions and outcomes reported in the included studies.

  • *Artunay 200935 studied patients with the following conditions: AMD, CNV due to myopic degeneration idiopathic and other secondary causes, cystoid or diffuse MO from CRVO, BRVO, diabetes, uveitis and retinitis pigmentosa proliferative retinopathies.

  • †Population included patients CNV due to AMD, DMO, DR, MO due to RVO or autoimmune retinopathy.

  • ‡Forty-seven patients out of a study population of 71 received bevacizumab. A number of patients received all three anti-VEGF medications while others received just one treatment type. However, authors reported that only the first anti-VEGF injection was considered in the study.

  • §Gamulescu (2010)51 included a control group that received ranibizumab.

  • ¶Re-injection in five eyes, 1 or 2 months after first injection at physician discretion.

  • **Good et al31 included a control group that received ranibizumab.

  • ††101 eyes received bevacizumab only, 96 eyes received ranibizumab only and 18 eyes received bevacizumab and ranibizumab.

  • ‡‡Population included patients AMD, diabetes, retinal vein occlusion and other eye conditions.

  • §§Kiss et al66 included a control group that received triamcinolone acetonide.

  • ¶¶Krishnan et al69 included a control group that received ranibizumab.

  • ***Population included patients with AMD, BRVO, CRVO and myopic choroidal neovascularisation.

  • †††Population included patients with neovascular AMD; BRVO, CRVO; cystoid macular oedema; proliferative DR and DMO.

  • ‡‡‡Rasier et al77 reported between-group comparison of hypertensive/non-hypertensive patients.

  • §§§Conditions included AMD, DR, CNV, BRVO, CRVO and other pathologies (unspecified).

  • ¶¶¶Control group received triamcinolone acetonide.

  • ****Control group received triamcinolone acetonide.

  • AMD, age-related macular degeneration; BP, blood pressure; BRVO, branch retinal vein occlusion; CRVO, central retinal vein occlusion; CMO, cystoid macular oedema; CNV, choroidal neovascularisation; DMO, diabetic macular oedema; DR, diabetic retinopathy; FA, fluorescein angiography; IVB, intravitreal bevacizumab; IVP, intravitreal pegaptinib; IVR, intravitreal ranibizumab; MO, macular oedema; NA, not applicable, NR, not reported; OCT, optical coherence tomography; PDT, photodynamic therapy; RVO, retinal vein occlusion; PED, pigment epithelium detachment.