Despite treatment advances, diabetic eye disease remains a leading cause of visual acuity (VA) loss worldwide. No methods to prospectively determine which patients will gain or lose vision exist, limiting individualized risk assessment and management. We investigated whether noninvasive, readily obtainable spectral domain optical coherence tomography parameters were correlated with VA in eyes with current or resolved center-involved diabetic macular edema (DME). Images were evaluated for disorganization of the retinal inner layers (DRIL), cysts, epiretinal membranes, microaneurysms, subretinal fluid, and outer layer disruption/reflectivity. DRIL affecting ≥50% of the 1-mm central retinal zone was associated with worse VA in all eyes, eyes with current edema, and eyes with resolved edema. Furthermore, early 4-month change in DRIL extent predicted VA change from baseline to 1 year. These data suggest that DRIL is a robust predictor of VA in eyes with present or previous DME and more highly correlated with VA than other widely used measures, such as retinal thickness. If further studies confirm DRIL as a predictive biomarker of future VA, physicians would gain a new tool of substantial clinical and investigative importance that could significantly change the approach to ophthalmic counseling and therapeutic management in patients with diabetes.