Abstract
Purpose :
To phenotype DME based on anatomical response to anti-VEGF and evaluate the predictive value of in vitro readouts of iPSC-ECs.
Methods :
Medical records and serial optical coherence tomography scans of consecutive patients with DME initiating treatment with Ranibizumab at the Belfast Trust between March and December 2014 were reviewed. Patients were eligible if they had received a loading dose (three injections) and were followed for at least 12 months. Based on the treatment response patients were classified as “responders” (retina fully dry at any time during the course of treatment), “partial responders” (fluid decreased but never cleared) or “non-responders” (fluid unchanged). Differences in clinical characteristics among the three groups were statistically sought. iPSCs were generated from blood cells obtained from three "responders" and three "non-responders" and differentiated into ECs. Phosphorylation of the VEGF receptor (VEGFR2) and gene expression profiles were evaluated in these groups.
Results :
There were 100 DME patients (140 eyes), classified as “responders” (45 eyes, 32%), “partial responders” (86 eyes, 61%) or “non-responders" (9 eyes, 6%) with no differences in clinical characteristics among them. When stimulated with VEGF, “non-responders” derived iPSC-ECs showed increased VEGFR2 phosphorylation when compared with “responders”. Furthermore, gene expression profiles of iPSC-ECs from “responders” and “non-responders” demonstrated a number of differentially expressed gene transcripts that were linked with cell permeability and VEGF signalling.
Conclusions :
In only ~ a third of patients DME fully cleared after a minimum of one year of treatment suggesting that other mechanisms besides VEGF-induced leakage are involved in DME in many patients. Patient-specific iPSC-EC responses in vitro differred between "responders" and "non-responders". This “patient-in-a dish” approach has potential to be used to predict clinical responses to anti-VEGF therapy in DME.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.