PURPOSE: To investigate the incidence, clinical spectrum, and pathophysiology of microcystoid macular edema (MME) in 2 cohorts of patients with epiretinal membrane (ERM) and idiopathic full-thickness macular hole (FTMH). DESIGN: Single-center, retrospective, interventional, cohort study. METHODS: Review of clinical charts, structural and en-face optical coherence tomography (OCT), and fluorescein angiography (FA) imaging of ERM and FTMH eyes that underwent surgery with pars plana vitrectomy and internal limiting membrane (ILM) peel, with a minimum follow-up of 6 months. Histopathology analysis of 3 specimens: 2 human retinas and 1 human ILM. RESULTS: One hundred seventy-two patients with ERM (123) and FTMH (49) were included in the study and followed up a mean of 9.1 ± 4.7 and of 8.2 ± 3.6 months, respectively. Preoperatively, MME was present in 27 of 123 eyes with ERM (21.9%), and in none of 49 eyes with FTMH (P <
.001). MME was significantly associated with advanced ERM stages (P <
.001). MME was typically located below continuous ERM-ILM adherence areas. FA in 46 ERM eyes showed capillary leakage in 36.4% of eyes without MME or cystoid macular edema (CME), in 39% of eyes with MME, and increased hyperfluorescence in CME. Postoperatively, new-onset MME appeared in 13 of 84 ERM eyes (15.5%) and in 1 FTMH eye (2%, P = .014). MME resolved in 7 of 40 ERM eyes with either preoperative or postoperative MME (17.9%) by 2.8 ± 1.5 months postsurgery. MME showed variable evolution postoperatively. The association between MME and postoperative best corrected visual acuity was significant only in univariate analysis (P = .037). Histopathology analysis showed anatomical continuity between Müller cells and ERM, suggesting a higher risk of iatrogenic damage in ERM eyes during peeling maneuvers. CONCLUSIONS: Postoperative MME was a frequent finding in ERM and a rare occurrence in FTMH, suggesting that ILM peeling alone may not be sufficient to cause MME. The morphology and clinical characteristics of ERM-related MME are unlikely related to neurodegenerative processes and rather attributable to Müller cell disruption and iatrogenic damage. The characteristics of MME and CME may overlap, blurring the differences between the 2 entities.