Development of a drug-eluting intraocular lens to deliver epidermal growth factor receptor inhibitor gefitinib for posterior capsule opacification prophylaxis.

PURPOSE: Different molecular targets, such as the epidermal growth factor receptor, have been identified for the prophylaxis of posterior capsule opacification. This led to the proposal of several drugs, yet drug delivery into the capsular bag remains challenging. The intraocular lens as a drug delivery device would provide a convenient method to allow drug release in the location needed. This is to evaluate the effect of a drug-eluting intraocular lens using an epidermal growth factor receptor inhibitor. METHODS: Hydrophobic and hydrophilic intraocular lenses were coated with gefitinib using the dip coating technique. The cellular response on the modified intraocular lenses was tested in a human lens epithelial cell line (FHL-124) in an anterior segment model. Furthermore, modified intraocular lenses were implanted into human capsular bags ex vivo. Drug release was determined as well as the biocompatibility on human corneal endothelial cells. Unmodified intraocular lenses served as controls. In addition, immunofluorescence staining with fibronectin as a marker for fibrotic response was conducted. RESULTS: Both coated hydrophilic and hydrophobic intraocular lenses could attenuate the cell growth of FHL-124 cells in the human capsular bag in comparison to the unmodified controls. Furthermore, gefitinib-soaked intraocular lenses showed a constant drug release over the first 10 days. No reduction in cell viability of corneal endothelial cells occurred. A decrease in fibronectin expression under gefitinib treatment could be observed. CONCLUSION: In vitro epidermal growth factor receptor seems to be a valuable target for the prevention of posterior capsule opacification. The gefitinib-eluting intraocular lens in this study could inhibit cell growth in non-toxic concentrations.

The intraocular lens as a drug delivery device for an epidermal growth factor-Receptor inhibitor for prophylaxis of posterior capsule opacification.

PURPOSE: Posterior capsule opacification (PCO) occurs as a common complication after cataract surgery. Erlotinib is an inhibitor of the epidermal growth factor-Receptor and reduces critical cellular events leading to PCO. In this in vitro study, Erlotinib-modified intraocular lenses (IOLs) employed as a drug delivery device have been evaluated for PCO prevention. METHODS: The IC50 concentration of Erlotinib was determined by using FHL-124 cells. For the human capsular bag model, 40 cadaver eyes underwent sham cataract surgery. Sixteen capsular bags were exposed to the IC50 of Erlotinib. Intraocular lens (IOL) of three different materials was pharmacologically modified and tested in the anterior segment model and implanted into 24 capsular bags. To test for corneal toxicity, pairs of human cornea were exposed to high concentrations of Erlotinib and corneal endothelial cells (CEC) were exposed to the modified IOL. Release kinetics of Erlotinib from the IOL was measured. RESULTS: IC50 of Erlotinib was determined to be 10 µm. Erlotinib alone (p = 0.002) and when soaked into IOLs (p < 0.001) significantly increased the number of days needed until total cell coverage of the capsular bags in comparison with the control. Modified IOLs mitigated cell growth in the anterior segment model (p < 0.001). No short-term corneal toxicity was observed up to a concentration of 100 µm, and IOLs did not show toxicity on CEC. Erlotinib was released constantly from IOL. CONCLUSION: Erlotinib might be of clinical relevance in PCO prophylaxis, as its short-term application induces a long-term deceleration of cellular growth. Erlotinib can be introduced into the eye via soaked IOLs.

A cell culture technique for human epiretinal membranes to describe cell behavior and membrane contraction in vitro.

PURPOSE: To introduce a human cell culture technique for investigating in-vitro behavior of primary epiretinal cells and membrane contraction of fibrocellular tissue surgically removed from eyes with idiopathic macular pucker. METHODS: Human epiretinal membranes were harvested from ten eyes with idiopathic macular pucker during standard vitrectomy. Specimens were fixed on cell culture plastic using small entomological pins to apply horizontal stress to the tissue, and then transferred to standard cell culture conditions. Cell behavior of 400 epiretinal cells from 10 epiretinal membranes was observed in time-lapse microscopy and analyzed in terms of cell migration, cell velocity, and membrane contraction. Immunocytochemistry was performed for cell type-specific antigens. RESULTS: Cell specific differences in migration behavior were observed comprising two phenotypes: (PT1) epiretinal cells moving fast, less directly, with small round phenotype and (PT2) epiretinal cells moving slowly, directly, with elongated large phenotype. No mitosis, no outgrowth and no migration onto the plastic were seen. Horizontal contraction measurements showed variation between specimens. Masses of epiretinal cells with a myofibroblast-like phenotype expressed cytoplasmatic α-SMA stress fibers and correlated with cell behavior characteristics (PT2). Fast moving epiretinal cells (PT1) were identified as microglia by immunostaining. CONCLUSIONS: This in-vitro technique using traction application allows for culturing surgically removed epiretinal membranes from eyes with idiopathic macular pucker, demonstrating cell behavior and membrane contraction of primary human epiretinal cells. Our findings emphasize the abundance of myofibroblasts, the presence of microglia and specific differences of cell behavior in these membranes. This technique has the potential to improve the understanding of pathologies at the vitreomacular interface and might be helpful in establishing anti-fibrotic treatment strategies.