Exudative age related macular degeneration (wet AMD) is a leading cause of vision loss in the western world, and current therapy requires monthly injection into the eye of anti-vascular endothelial growth factor (VEGF) proteins. VEGF is generated as two isoform families by alternative splicing – pro-angiogenic and anti-angiogenic. Retinal pigmented epithelial (RPE) cells require serine-rich protein kinase-1 (SRPK1) to phosphorylate serine/arginine-rich splicing factor-1 (SRSF1) to induce alternative splicing that generates pro-angiogenic isoforms. We tested the hypothesis that SRPK1 selective inhibitors could be generated that reduce pro-angiogenic isoforms, and that SRPK1 inhibitors could be administered topically to prevent choroidal neovascularisation. Novel SR Phosphorylation Inhibitors, (SPHINXs) were tested for SRPK inhibition in vitro, pro-angiogenic VEGF production in RPE cells by PCR and ELISA, and for inhibition of choroidal neovascularisation induced by laser photocoagulation in mice and rats. A novel disubstituted furan inhibitor, SPHINX, was selective for the SRPK family of kinases targeting SRPK1 with an IC50 <1μM (Hills model of regression; log (inhibitor) vs. response – variable slope) and reduced the expression of pro-angiogenic but not anti-angiogenic VEGF isoforms. Choroidal neovascularisation was significantly reduced in vivo by SPHINX (0.039±0.026mm2; n=5) and the known SRPK inhibitor SRPIN340 (0.038±0.008mm2; n=5), compared with vehicle controls (0.11±0.016mm2; p<0.05, One-way ANOVA, Bonferonni post hoc). Topical administration of SPHINX and SRPIN340 significantly inhibited CNV to 38.5±7.4% (n=5) and 53.6±8.5% (n=6) of control respectively (p<0.05, One-way ANOVA, Bonferonni post hoc). These results indicate that novel SRPK1 selective inhibitors could be potential novel topical (eye drop) therapeutics for wet AMD.