Abstract
Purpose: :
Blood–aequeous barrier breakdown has been reported after topical and intraocular application of various drugs. For example, injection of aliphatic rhuFab formulations have caused a marked increase in Tyndall and cellular infiltration in the anterior chamber. We wanted to post these safety issues for Bevacizumab (AvastinTM), a humanized monoclonal anti–VEGF antibody originally developed for intravenous therapy of metastatic cancer, but now beeing used as promising drug in neovascular age–related macular degeneration (AMD).
Methods: :
The anterior chamber reaction was analyzed in a subgroup of 43 patients receiving 1mg of intravitreal Bevacizumab (AvastinTM) for the treatment of edematous or neovascular maculopathy. Aqueous humour flare was measured with the laser flare meter (FC–500, Kowa Co. Ltd, Tokyo, Japan) 30 minutes after dilatation of the pupils. Routine testing was performed at baseline, 1st postoperative, after 1 week and 1 month, totally independent from the time point or clinical course. Each flare measurement was repeated ten times and the readings were accepted only if the two sampling windows of background flare were within 15%. The mean of 10 readings was calculated for each value at a given time. Flare values were expressed as photon counts per millisecond (ph/ms).
Results: :
The mean flare values were 10.4 ph/ms (mean SD 2.4, 95%–CI 8.0–12.8) at baseline, declining to 8.8 ph/ms (mean SD 2.8, 95%–CI 7.5–10.2) after 1 week and, 8.3 ph/ms (mean SD 1.4, 95%–CI 7.0–9.6) after 1 month. An increase in anterior flare at the first postoperative day was only seen in 55.9% (24 of 43) patients (mean 10.3 ph/ms, 95%–CI 8.7–12.0). The decrease of flare after 1 month was significant (each pair, Student's t, p<0.001). Updated data will be presented at the meeting.
Conclusions: :
Higher flare values at baseline than in age–matched controls indicated a pre–existing disruption of the blood–aequeous barrier. Intravitreous injection of Bevacizumb did not cause a significant elevation of the aqueous humour opalescence. The decrease of flare values in the time course might be related to the pharmacodynamic effects of the drug lowering the permeability of iris and retinal blood vessels. Further examinations have to evaluate whether the flare value could be used as a non–invasive indicator for the drug effect (in time course) or the effective concentration in individual cases.
Keywords: anterior chamber • inflammation • drug toxicity/drug effects