PurposeThe differential diagnosis between Irvine‐Gass Syndrome (IGS) and Diabetic Macular Edema (DME) is currently established by angiography, which is an invasive and time‐consuming tool. The aim of this study is to evaluate differences in optic disc's nerve fiber layer thickness (RNFL) in patients with macular edema associated with IGS and Diabetes Mellitus (DM).MethodsRetrospective case control study of 28 eyes of 28 patients with macular edema divided into 2 groups. Group 1 included 14 eyes with IGS diagnosed by clinical and angiographic criteria and group 2 included 14 eyes with cystoid diabetic macular edema (DME) without previous ocular surgery. A control group (group 3) of 14 eyes of 14 healthy patients paired by age and gender were also included. Ophthalmologic examinations included visual acuity (VA) measurements, slit‐lamp examination, Goldmann applanation tonometry, Spectral‐Domain Optic Coherence Tomography (SD‐OCT) and fluorescein angiography.ResultsForty two patients (21 females and 21 males), with a mean age of 66.57 ± 10.80 years were included in this study. Optic disc nasal and temporal RNFL thicknesses as well as central macular thickness were significantly higher in group 1 and 2 compared with control group (p < 0.05). Nasal RNFL thickness was higher in IGS than in patients with DME (p < 0.001). To detect IGS (Group 1), comparative to DME (Group 2), using Nasal RNFL thickness, the area under the curve was 0.842 p < 0.002. A cut‐off criterion of 82.50 μm resulted in 92.9% sensitivity and 71.4% specificity.ConclusionsOptic disc SD‐ OCT imaging might be a useful diagnostic tool to differentiate IGS from DME.