Serum Levels of Intravitreal Bevacizumab After Vitrectomy, Lensectomy and Non-Surgical Controls

Abstract

Purpose To determine serum level differences of intravitreally-placed bevacizumab after vitrectomy and lensectomy-vitrectomy and to compare these with non-operated eyes in a rabbit model. Methods Five Dutch-belted rabbits underwent pars plana vitrectomy (PPV), 5 rabbits underwent pars plana lensectomy (PPL) and 5 rabbits served as non-surgical controls. Twelve days following the surgical procedures, each operated eye underwent an intravitreal injection consisting of 1.25 mg/0.05 mL bevacizumab. Serum levels from each rabbit were drawn on days 2, 4, 7, 10, 14, 21, 28 and 35 and were measured with ELISA immunoassay. Results The average peak serum concentration (Cmax) was highest for the PPL group (11.33 µg ± 3.48 mL), and was similar between the PPV (5.35 µg ± 2.69 mL) and non-surgical control groups (5.35 µg ± 0.69 mL). The average time to maximal plasma concentration (Tmax) in days was earliest for the PPL group (2.8 ± 0.47), followed by the PPV (5.6 ± 0.84) and non-surgical control groups (6.4 ± 0.71). The PPL group had higher serum levels than the other 2 groups until day 7 that was significant only at day 2 (p<0.0001). After day 4 there were no significant differences or trends between any of the 3 groups. The half-life (T1/2) was fastest for the PPL group (1.41±0.21 days) followed by the PPV (2.80±3.35 days) and non-surgical control groups (6.69±10.4 days). Conclusions Serum bevacizumab levels were initially elevated following lensectomy and vitrectomy compared to non-surgical eyes following intravitreal injection. The half-life of bevacizumab was prolonged in non-surgical eyes presumably due to a slower release from the vitreous cavity.

The Role of Epiretinal Membrane on Treatment of Neovascular Age‐Related Macular Degeneration with Intravitreal Bevacizumab

“…However, this series had a small number of patients to conclude. In addition, vitrectomy in such eyes can result in complications and may also complicate anti-VEGF treatment, as it may shortens the half-life of intravitreal anti-VEGF drugs, so that higher doses and more frequent injections of anti-VEGF drugs may be needed postoperatively [ 32 , 33 ]. Based on these findings, none of the patients in our study had vitrectomy for ERM peeling during the study period.…”

Influence of the epiretinal membrane on ranibizumab therapy outcomes in patients with diabetic macular edema

“…However, the use of PPV in such eyes can lead to complications and might also affect anti-VEGF treatment by reducing the half-lives of intravitreal anti-VEGF drugs; as a result, higher doses and more frequent injections of anti-VEGF drugs might be needed postoperatively (16,17) . Although rare, the spontaneous resolution of VMT after IVR has been reported in patients with DME (18) .…”

Pharmacokinetics of Intravitreal Anti-VEGF Drugs in Age-Related Macular Degeneration

“…A study performed on rabbits with labelled mAbs with I-124 demonstrated a reduction in the half-life of anti-VEGF drugs after vitrectomy and lensectomy, going from 4.22 to 2.30 and 2.08 days, respectively, for bevacizumab and from 2.81 to 2.13 and 1.79 days, respectively, for ranibizumab [60]. The same author also quantified the serum concentration of bevacizumab in rabbits, finding that the serum levels initially increased following the vitrectomy, but determining that there were not any significant differences later on [61]. On the contrary, other authors did not find significant differences on the vitreous half-life on injected bevacizumab in non-vitrectomised vs vitrectomised eyes in rabbit eyes (7.06 days vs 6.99 days) [62], which suggested that VEGF is a complex molecule that is not restricted to the elimination by diffusion.…”