While short-term effects of anti-vascular endothelial growth factor (anti-VEGF) therapy on retinal pigment epithelial (RPE) cells have been studied, long-term and repeated treatment effects have received less attention in the literature. With this in mind, a team of German researchers found promising results in patients who received anti-VEGF treatments over a 12-week period.¹ The study, first reported in Experimental Eye Research, found long-term anti-VEGF treatment was not toxic nor did it induce premature aging in RPE during the three months.¹

The investigators conducted the experiments in primary porcine RPE cells, which were treated with 125μg/ml bevacizumab, ranibizumab, aflibercept or rituximab once a week for one day, four days, seven days, four weeks and 12 weeks.

Researchers found treatment up to 12 weeks caused no toxic effects on RPE cells in any of the substances tested. Ranibizumab showed a significant increase in β-galactosidase signal on day four and seven after treatment. Long-term, however, ranibizumab displayed no significant difference to untreated cells. Bevacizumab displayed a significant reduction of the β-galactosidase signal after 12 weeks. Aflibercept significantly decreased β-galactosidase after one day and 12 weeks. Rituximab and bevacizumab also decreased β-galactosidase signal after 12 weeks.

Additionally, researchers found long-term treatment did not change mitochondria ultrastructure in RPE, and that anti-VEGF compounds differ in their influence on autophagosomes.

“Taken together, our data provide indications for long-term safety of anti-VEGF compounds. Further research is warranted,” the researchers said.

1. Schottler J, Randoll N, Lucius R, et al. Long-term treatment with anti-VEGF does not induce cell aging in primary retinal pigment epithelium. Exp Eye Res. 2018 Jun;171:1-11.