IMPORTANCE: Macular edema (ME) prognosis and treatment response vary according to the underlying abnormalities. Biomarkers of visual acuity (VA) improvement could influence management decisions in different types of ME. OBJECTIVE: To investigate whether disorganization of retinal inner layers (DRIL) and other spectral-domain optical coherence tomography (SD-OCT)-derived variables are associated with subsequent VA after ME resolution in both nondiabetic and diabetic ME. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, longitudinal cohort study in which Snellen VA testing and SD-OCT macular imaging were performed, was conducted at a tertiary referral eye center for retinal diseases. The medical records of all patients with ME from December 1, 2010, to December 31, 2012, were reviewed. The date of the last follow-up was June 1, 2013. Participants included 55 patients (70 eyes) with center-involved ME that had resolved during an 8-month period. Patients were grouped based on the source of ME (diabetic vs nondiabetic). Exclusion criteria included significant media opacity interfering with good-quality SD-OCT image acquisition. Masked graders analyzed the central 1500-μm macular region for changes, including cysts, DRIL length and extent, and outer retinal layers disruption. Intragrader and intergrader agreement Spearman rank correlation coefficients ranged from 0.70 to 0.93 for quantitative measurement, and κ values ranged from 0.88 to 1.00 for qualitative grading. MAIN OUTCOMES AND MEASURES: Visual acuity and morphologic changes measured on SD-OCT. RESULTS: In both groups, VA after ME resolution correlated with baseline VA. In diabetic ME involving a multivariable model including baseline VA and DRIL, total length was associated with subsequent VA as determined by a parameter estimate (PE) of 0.0003 (95% CI, 0-0.0006) (P = .03). The VA change during the 8-month period, after adjusting for baseline VA, was best associated with DRIL change (PE, 0.0002 [95% CI, 0-0.0003]; P = .04). Participants whose DRIL resolved, both early and late, showed improvement in their VA deficit at 8 months (least squares mean [SE], 41.3 [28.5] and 40.9 [37.5], respectively) compared with nonresolvers, whether inconsistent or persistent, whose VA worsened. After adjustment for baseline VA, eyes with persistent DRIL showed the largest difference in VA deficit compared with those with no baseline DRIL (-89.6 [27.2] vs 49.7 [19.6], respectively; P = .006). CONCLUSIONS AND RELEVANCE: The presence of DRIL at baseline and its resolution pattern may be associated with subsequent VA after resolution of center-involved diabetic ME.