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Nick Pongsthorn Piravej[/caption]
Intraocular lenses (IOLs) as a drug delivery device soaked with gefitinib, a drug used to treat cancer, may one day help inhibit posterior capsule opacification (PCO) after cataract surgery, Nick Pongsthorn Piravej and his group (Prof Kirsten Eibl-Lindner, Christian Wertheimer MD and Alexander Kueres) told the XXXIV Congress of the ESCRS in Copenhagen, Denmark.
In an established in vitro anterior chamber PCO model (
Gotoh N et al. Invest Ophthalmol Vis Sci 2007;48:4679-87) tested at the University of Munich, Germany, gefitinib-soaked IOLs reduced the area covered by lens epithelial cells (LECs) by 60% to 80% compared with non-treated IOLs, Mr Piravej reported. In addition to reducing PCO, the test suggests that IOLs may be a viable long-term delivery system for intraocular drugs using a principle similar to drug-eluting cardiac stents or the Ozurdex intravitreal implant.
INHIBITING EGFR
Gefitinib blocks the epidermal growth factor receptor (EGFR) protein on cell surfaces, which plays a key role in PCO development, Mr Piravej said. Blocking EGFR prevents the binding of epidermal growth factor which otherwise would promote LEC proliferation. Inhibiting EGFR also blocks downstream signalling supporting LEC proliferation and migration. “So we are looking at the possibility of introducing gefitinib to the eye,” Mr Piravej said.
Hydrophilic, hydrophobic and hydrophilic with hydrophobic surface IOLs were soaked in a gefitinib solution long enough for the drug to permeate the polymer. The soaked IOLs and non-soaked controls were placed on a semi-permeable membrane covering a dish of cell culture medium with a weight on top firmly pressing the lens posterior surface against the membrane, simulating conditions in the capsular bag.
CELL GROWTH
The IOL and membrane were seeded with human LECs and incubated for 72 hours. The IOLs were removed, stained and analysed with an electronic sensor that counted pixels above a colour threshold, yielding an area measurement proportional to LEC growth across the membrane.
Cell growth reached 100% coverage in all control IOLs, Mr Piravej said. By comparison, coverage reached about 40% in hydrophilic and hydrophilic with hydrophobic surface, and about 20% in hydrophobic lenses.
How long and at what concentration gefitinib is released is unknown, though early indications are the effect is long-lasting. Mr Piravej suggested moving to animal model tests.
“Gefitinib treatment is one of the promising ways to reduce PCO because it inhibits cell proliferation and migration,” Mr Piravej said, adding that IOL delivery is attractive because it requires no additional surgical steps or interventions.
Nick Pongsthorn Piravej: Nick.Piravej@med.uni-muenchen.de