Aims To characterise differential pathogeneses of diabetic macular oedema (DMO) using ultra-widefield fluorescein angiography (UWFA) and evaluate responses to anti-vascular endothelial growth factor (anti-VEGF) therapy.

Methods Ninety-nine eyes (73 consecutive patients) with anti-VEGF naïve DMO underwent UWFA and optical coherence tomography, of which 60 with central retinal thickness (CRT) >400 μm received monthly intravitreal ranibizumab injections. Best-corrected visual acuity (BCVA) and CRT were measured at baseline and after three injections.

Results After excluding tractional factors, DMO was categorised into three types based on UWFA: (A) microaneurysm driven (49%), (B) peripheral ischaemia (37%) and (C) neovascularisation (15%). While all three types showed similar mean CRT (p=0.257), types B and C were associated with more diffuse oedema, which extended beyond the 6.0 mm central macula (p=0.0034). Following anti-VEGF treatment, all three types showed improvement in CRT and BCVA, which reached statistical significance for types A and B. A positive correlation was found between the Peripheral Ischaemia Index and improvement in CRT (slope=2.09, R²=0.1169, p=0.0151) but not BCVA (slope=−0.00037, R²=0.001149, p=0.8152).

Conclusions UWFA facilitates the detection of peripheral ischaemia, which is associated with a significant proportion of DMO. While this group of DMO responded well to anti-VEGF therapy, it remains to be determined whether addressing the peripheral ischaemia may reduce recurrence.