In a cross-sectional study, 34 diabetic patients with clinically significant macular edema underwent visual acuity testing, stereo fundus photography (graded for retinal thickening and hard exudates), fluorescein angiography (evaluated for macular leakage and the outline of the foveal avascular zone [FAZ]), and vitreous fluorophotometry (whereby posterior penetration ratios were calculated). This last ratio provided the highest single correlation with visual acuity; next highest were patient age and FAZ grading. Multivariate regression confirmed that these three variables together best predicted visual acuity. Lesser correlations with acuity were obtained with angiographic leakage and fundus photography grading. Cross-correlations among all gradings showed that indicators of breakdown of the blood-retinal barrier, ie, fluorophotometry, angiographic leakage, and retinal thickening, were significantly correlated with each other, whereas FAZ grading was independent of all these factors and correlated only with acuity. By performing vitreous fluorophotometry and fluorescein angiography, it is possible to quantitate two major components of diabetic maculopathy: breakdown of the blood-retinal barrier and macular ischemia, both of which are highly correlated with visual acuity.