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Purpose To evaluate a region of interest (ROI) method of analyzing anterior segment optical coherence tomography (AS-OCT) corneal densitometry (CD) in the setting of Descemet membrane endothelial keratoplasty (DMEK) dehiscence. Methods Retrospective chart review of eyes that underwent (1) DMEK for Fuchs dystrophy (2) between 2018 to 2020 with (3) a partial DMEK dehiscence on AS-OCT, (4) involvement of only one side of the graft, (5) high-quality corneal AS-OCT scan, and (6) location of dehiscence within the central 5.5 mm of the cornea. Image analysis of the ROIs with ImageJ compared the total edematous area, mean stromal CD, and ratio of anterior-to-posterior (A/P) stromal CD for regions of DMEK dehiscence compared to the contralateral side with an attached DMEK graft. Control regions (with no dehiscence) and postdehiscence resolution images were also analyzed. Results Seventy sectors of the 21 images from 21 eyes with DMEK dehiscence were included. Compared to the contralateral side, regions of DMEK dehiscence had larger total areas (P < 0.0001), lower mean stromal CD (P = 0.0003), and higher A/P stromal CD (P < 0.0001). All control regions and postdehiscence resolution images did not show any significant differences compared to the contralateral sides. Conclusions This technique to analyze multiple ROIs on AS-OCT can be useful to evaluate CD of specific regions of corneal pathology. Lower mean stromal CD and higher A/P stromal CD may specify corneal edema. Translational Relevance Analyzing CD via multiple specific ROIs may be more suitable than measuring the CD of the full cornea and has broader applications extending to other corneal pathologies.