Objective: To assess the changes occurring at the vireoretinal interface with clinically significant macular edema using optical coherent tomography (OCT) and fundus fluorescein angiography (FFA).    Patients and Methods:   Ninety nine eyes of 84 patients suffering from macular edema of different etiologies were included in this study. They were divided according to the cause of macular edema into 6 groups. Treatment modalities were done to be evaluated in the follow up. All cases were followed up at regular visits one week, one month, and six months with routine ocular examinations. FFA and OCT changes were determined and evaluated at one month and 6 months after treatment.     Results: In diabetic group (40 eyes), there were 22 eyes  with different stages of PVD seen by OCT in comparison to 5 eyes only demonstrated by FFA, ERM seen by OCT of different stages in 14 eyes while in FFA 10 eyes only, In the RVO group (15 eyes), there were 6 eyes with different stages of PVD seen by OCT in comparison to no eyes demonstrated by FFA, In the IGS group (10 eyes), there were 3 eyes with different stages of PVD seen by OCT in comparison to no eyes demonstrated by FFA, In the CNV group (17 eyes), there were 4 eyes with different stages of PVD seen by OCT in comparison to no eyes demonstrated by FFA, ERM seen by OCT of different stages in 3 eyes while in FFA one eye only, In the RP group (10 eyes), there were 2 eyes with different stages of PVD seen by OCT in comparison to no eyes demonstrated by FFA. In the TME group (7 eyes), there were 3 eyes with different stages of PVD seen by OCT in comparison to no eyes demonstrated by FFA, ERM seen by OCT and FFA of different stages in 4 eyes.   Conclusions: OCT provided us with valuable information on the retinal morphologic changes associated with ME of different etiologies and analyzing vitreomacular relationship and detecting macular SRD undetectable on biomicroscopy and FFA.