Diabetic macular
edema (DME) remains a leading cause of vision loss worldwide. DME is commonly treated
with intravitreal injections of vascular endothelial growth factor (VEGF)
neutralising antibodies. Anti-VEGFs are
effective but not all patients fully respond to them. Given their potential side effects, inconvenience
and high cost, identifying who may not respond appropriately to anti-VEGFs and
why is essential.
<p>Herein, we determine first the
response to anti-VEGFs in a cohort of DME patients using spectral-domain optical coherence tomography scans
obtained throughout the first year of treatment. We found that in 28% of eyes full clearance
of fluid occurred at any time during the first year (“full responders”); in 66%
fluid cleared only partly (“partial responders”); in 6% fluid remained
unchanged (“non-responders”). To understand this differential response, we generated
induced pluripotent stem cells (iPS) from “full responders” and “non-responders”
and from diabetic subjects with no DME and age-matched non-diabetic volunteers
and differentiated them into endothelial cells (iPS-ECs). Monolayers of iPS-ECs derived from diabetics
showed marked and prolonged increased permeability upon exposure to VEGF when
compared with non-diabetic controls; the response was significantly exaggerated
in iPS-ECs from “non-responders” when compared with “full responders”. Moreover,
phosphorylation of key cellular proteins in response to VEGF, including VEGFR2,
and gene expression profiles, such as Neuronal
Pentraxin 2 (NPTX2) expression, differed between “full responders” and
“non-responders”. </p>
<p>In
the current study, iPS were used to predict patient response to anti-VEGF and identify
key mechanisms underpinning the differential outcomes observed in the clinic.
This approach has identified NPTX2 as playing a significant role in
patient-linked responses and has potential as a new therapeutic target for DME.
</p>
Subthreshold micropulse laser versus intravitreal anti-VEGF for diabetic macular edema patients with relatively better visual acuity
