Twelve-month safety of intravitreal injections of bevacizumab (Avastin): results of the Pan-American Collaborative Retina Study Group (PACORES).
BACKGROUND
Vascular endothelial growth factor (VEGF) plays an important role in many diseases of the posterior pole that are characterized by macular edema and/or intraocular neovascularization. Recently anti-VEGF agents such as ranibizumab and pegaptanib sodium have been shown to be beneficial in the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (ARMD). However in most parts of the world, both pegaptanib sodium and ranibizumab are not readily available. Bevacizumab, a humanized recombinant monoclonal IgG antibody that binds and inhibits all VEGF isoforms, has been proposed as an alternative treatment option.


METHODS
A total of 1,265 consecutive patients were injected with bevacizumab for diseases such as proliferative diabetic retinopathy, diabetic macular edema, retinal vein occlusions, and CNV of several etiologies including ARMD at eight Latin American institutions from 1 September 2005 to 31 January 2006. Of these 1,265, 92 were excluded because they were injected once and lost to follow-up. The remaining 1,173 patients constitute the subjects of this retrospective, multicenter, open label, uncontrolled interventional case series that reports the cumulative systemic and ocular adverse events following intravitreal bevacizumab during 12 months of follow-up. Patients were examined at baseline and then monthly. If the patients were unable to attend the 12-month visit, a telephone interview was conducted to assess for possible systemic complications.


RESULTS
A total of 4,303 intravitreal injections of bevacizumab on 1,310 eyes was reported. All 1,173 patients were accounted for at the 12-month visit. Systemic adverse events were reported in 18 (1.5%) patients. These included seven (0.59%) cases of an acute elevation of systemic blood pressure, six (0.5%) cerebrovascular accidents, five (0.4%) myocardial infarctions, two (0.17%) iliac artery aneurysms, two (0.17%) toe amputations and five (0.4%) deaths. Ocular complications included seven (0.16%) bacterial endophthalmitis, seven (0.16%) tractional retinal detachments, four (0.09%) uveitis, and a case (0.02%) each of rhegmatogenous retinal detachment and vitreous hemorrhage.


CONCLUSIONS
Despite the limited follow-up, repeated intravitreal injections of either 1.25 mg or 2.5 mg of bevacizumab appears to be safe and well tolerated during the 1st year.
Instituto de Cirugía Ocular, San José, Costa Rica.
Lihteh
L
Wu
María A
MA
Martínez-Castellanos
Hugo
H
Quiroz-Mercado
J Fernando
JF
Arevalo
María H
MH
Berrocal
Michel E
ME
Farah
Mauricio
M
Maia
José A
JA
Roca
Francisco J
FJ
Rodriguez
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007267:Injections; D008268:Macular Degeneration / Q000188:drug therapy* / Q000503:physiopathology; D008269:Macular Edema / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012170:Retinal Vein Occlusion / Q000188:drug therapy* / Q000503:physiopathology; D019233:Retreatment; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity; D014822:Vitreous Body
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab