PURPOSE: To describe novel findings of hyperreflective material in the silicone-retina interphase on spectral domain optical coherence tomography (SD-OCT) imaging in eyes with silicone oil tamponade. METHODS: Retrospective observational clinical study of consecutive patients who underwent primary pars plana vitrectomy with silicone oil tamponade for rhegmatogenous retinal detachment. Repeat clinical examination and spectral domain optical coherence tomography macular imaging performed 3 months after surgery were evaluated to identify any macular pathologies, including formation of epiretinal membranes, intraretinal changes, subretinal fluid, and edema before scheduled secondary vitrectomy for silicone oil removal. RESULTS: Eighty-two patients (mean age 54 years, range 22-89) were included. Twelve eyes (14%) showed discrete preretinal hyperreflective organized coarse material in the silicone-retina interphase on spectral domain optical coherence tomography. The material was scattered in the posterior pole, with several foci showing additional hyperreflectivity of the inner retinal layers beneath. These findings did not resemble silicone oil emulsification in size, shape, or reflectivity. CONCLUSION: This is the first report on hyperreflective material detected by spectral domain optical coherence tomography in the silicone-retina interphase in eyes with silicone oil tamponade. These findings may represent an inflammatory response to silicone oil exposure that may be the initial manifestation of a future proliferative process, warranting a rigorous follow-up protocol for affected patients.