Purpose To analyse the topographic changes in retinal ganglion cells (RGCs) in eyes with unilateral naive branch retinal vein occlusion (BRVO) in comparison to normal fellow eyes and to healthy control eyes. Methods We performed a retrospective analysis of 66 eyes (33 subjects) with naive unilateral BRVO who underwent spectral-domain optical coherence tomography using Cirrus HD-OCT. We also included 67 eyes of 48 age-matched healthy volunteers as control group. Average, minimum and sectoral macular ganglion cell-inner plexiform layer (GCIPL) thickness, macular retinal nerve fibre layer (RNFL) thickness and outer retinal thickness were collected. Comparison of the GCIPL, RNFL and outer retinal thicknesses among study eyes, normal fellow eyes and control groups was performed. Results The average and minimum macular GCIPL thicknesses were constantly and diffusely reduced in BRVO compared with normal fellow eyes and healthy controls (p<0.001 for each GCIPL sector). The average macular RNFL thickness was reduced in BRVO eyes compared with normal fellow eyes (p=0.01) and tended to be lower than controls (p=0.07). The minimum RNFL thickness in eyes with BRVO was significantly reduced when compared with fellow eyes (p<0.001) and control eyes (p<0.001). The average outer retina thickness was thicker in BRVO eyes compared with both fellow eyes (p<0.001) and controls (p<0.001). Conclusions A significant reduction of the macular GCIPL and RNFL thicknesses was observed in eyes with BRVO. This finding is suggestive of RGCs degeneration; the neuroprotective effect of current therapeutic options might be an important consideration when evaluating treatment strategies and prognosticating visual outcome in BRVO eyes.