Sukanya Arunachalam, Wei-Sen Lam, Anna Nowak, Jeannette Creaney, Michael Millward, Sanjeevan Muruganandan, Cathy Read, Gary Lee, Fred Chen1
Purpose: AZD4547 is a selective ftbroblast growth factor receptor (FGFR)-1, -2 and -3 tyrosine kinase inhibitor being investigated as a second line single oral agent chemotherapy for malignant pleural mesothelioma (MPM). We report the interim 3 week ophthalmic outcome of AZD4547 in a phase II clini- cal trial (ACTRN12615001291572).
Methods: Twenty subjects were enrolled in stage one. Ophthalmic examination was performed before and 3 weeks after commencement of therapy. Assessments included ETDRS visual acuity (VA), intraocular pressure, fundus examination, retinal imaging with Optos camera (P200Tx, Optos plc, Dunfermline, UK) and spectral domain optical coherence tomography (SD-OCT, Spectralis HRA + OCT, Heidelberg Engineering, Heidelberg, Ger- many). Mean and standard deviation (SD) were reported. Paired t-test was used to determine signift- cance of change in central subfteld thickness (CST) and total macular volume (TMV) before and 3 weeks after treatment.
Results: Thirty-two eyes of 16 participants were analysed. Mean (SD) age was 71 (8) years. 15 were male. Baseline VA was 82(5) and this remained sta- ble at 3 weeks (p=0.45). CSTs were 228 (31) and
271 (46) ?m at baseline and 3 weeks (p<0.001), respectively. TMV increased from 8.28 (0.46) to 8.59 (0.49) mm3 at 3 weeks (p<0.001). SD-OCT showed variable severity of serous macular detachment. Conclusions: Serous detachment due to FGFR blockade could be mediated through retinal pigment epithelium toxicity and failure of the outer retinal blood-retinal barrier. Understanding the pathophys- iology involved in selective FGFR inhibitor-induced retinopathy may provide insights into other disease process with similar phenotype such as central serous retinopathy.