Alterations in the intraocular cytokine milieu after intravitreal bevacizumab.
OBJECTIVE
Several complications after intravitreal bevacizumab (IVB) treatment have been described including tears of the retinal pigment epithelium and tractional retinal detachment. The etiology of these complications remains unclear. The purpose of this study was to characterize changes in the intraocular levels of inflammatory cytokines after IVB as a possible explanation for these complications.


METHODS
Twenty-nine patients with proliferative diabetic retinopathy (PDR) undergoing pars plana vitrectomy (PPV) for vitreous hemorrhage (VH) with IVB pretreatment were prospectively enrolled. Aqueous humor samples were taken at the time of IVB pretreatment and approximately 1 week later at the time of PPV. Multiplex cytokine arrays were used to assay 20 different cytokines. Multivariate general linear regression was performed to determine differences in cytokine levels between the two study visits. Proportional hazards regression was performed to determine the relationship between cytokine levels at PPV and postoperative outcomes.


RESULTS
After treatment with IVB, vascular endothelial growth factor (VEGF) concentrations in the aqueous humor decreased (P = 0.0003), whereas the concentrations of IL-8 and transforming growth factor (TGF)-beta(2) increased after IVB (P < 0.03). The level of IL-8 at the time of PPV was associated with the occurrence of recurrent VH after surgery (hazard ratio, 1.32; P = 0.02).


CONCLUSIONS
Alterations in the intraocular inflammatory cytokine milieu occur after IVB injection, possibly as a compensatory mechanism in response to VEGF inhibition. The increased concentrations of inflammatory cytokines after IVB may be clinically significant and may be responsible for some of the complications after IVB.
Forooghian
Farzin
F
Clinical Trials Branch, Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1204, USA.
Kertes
Peter J
PJ
Eng
Kenneth T
KT
Agrón
Elvira
E
Chew
Emily Y
EY
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D001082:Aqueous Humor / Q000378:metabolism*; D000068258:Bevacizumab; D016207:Cytokines / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007267:Injections; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism; D014821:Vitrectomy; D014822:Vitreous Body; D014823:Vitreous Hemorrhage / Q000601:surgery
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab