PURPOSE: To evaluate the microstructural features of cytomegalovirus (CMV) retinitis by spectral domain optical coherence tomography (OCT). METHODS: Subjects were patients with macula-involving CMV retinitis with OCT imaging. The leading edge of retinitis in the macula was identified based on fundus imaging, and OCT findings were longitudinally evaluated in three areas: within the area of active retinitis, at the leading edge of retinitis, and just beyond the leading edge of retinitis. RESULTS: Optical coherence tomography imaging of macular CMV retinitis identified vitreous cells in 10 eyes (100%), posterior vitreous detachment in four eyes (40%), broad-based vitreomacular traction in one eye (10%), epiretinal membrane in eight eyes (80%), and lamellar hole-associated epiretinal proliferation associated with an atrophic hole in one eye (10%). Retinal architectural disruption, disruption of inner retinal layers, disruption of the external limiting membrane, and ellipsoid zone abnormalities were noted within the area of retinitis in all eyes and decreased in frequency and severity at and beyond the leading edge of retinitis, although all 10 eyes (100%) exhibited one of these abnormalities, especially outer retinal microabnormalities, beyond the leading edge of retinitis. CONCLUSION: Microstructural abnormalities were frequently noted on OCT of CMV retinitis, including within the retina beyond the leading edge of retinitis identified by corresponding fundus imaging. Outer retinal abnormalities were noted more frequently than inner retinal abnormalities beyond the leading edge of retinitis. These findings provide insight into the effects of CMV retinitis on retinal microstructure and potentially on vision and highlight the potential utility of OCT for monitoring microprogression of macula-involving CMV retinitis.