ObjectiveTo describe the sequential morphological changes of the outer retina after full-thickness macular hole formation, utilizing a novel, objective staging system based on optical coherence tomography (OCT), and to determine its association with baseline visual acuity, duration of symptoms, and postoperative visual acuity at 3 months. DesignRetrospective, observational, multicenter study. ParticipantsPatients with idiopathic full-thickness macular hole (FTMH) presenting to St. Michael’s Hospital, Toronto, Canada, and Retina Consultants of Texas, Houston, USA, from 2009-2022. MethodsThe medical charts of 1000 patients with FTMH were reviewed and those with at least two preoperative SD-OCTs were analyzed. A staging system was developed by assessing outer retinal morphology on successive SD-OCT central foveal scans. Main Outcome MeasuresSequential outer retinal morphological changes with SD-OCT over time and their association with baseline visual acuity, duration of symptoms, and postoperative functional outcomes. ResultsFifty-two eyes of 52 patients with a mean age of 65.4 ±8.4 years were included. Sequential outer retinal morphologic changes at the FTMH borders occurred in 4 distinct and reproducible stages as follows: Stage A: separation of the neurosensory retina from the RPE with the well-defined external limiting membrane (ELM), ellipsoid zone (EZ) and interdigitation zone (IDZ) (4/52, 7.6%); Stage B: thickening of EZ (27/52, 51.9%); Stage C: patchy (moth-eaten) photoreceptor loss (16/52, 30.7%) and Stage D: severe or complete loss of ISs and OSs and/or bare ELM (5/52, 9.6%). When assessing the preoperative OCT scans closest to the time of surgery, over a mean follow-up period of 288.9 days (SD 350.4,[5 -1841]), 28.8%(15/52 ) of eyes were in Stage B, 28.8% (15/52) were in Stage C and 42.3 %(22/52 ) were in Stage D.There was a statistically significant association between increasing stage at baseline and longer duration of macular hole symptoms (p=0.032) and worse visual acuity at baseline (p<0.001). Additionally, patients presenting with Stages B and C at the time point closest to surgery had better visual acuity outcomes three months postoperatively compared to those with Stage D(P=0.04). ConclusionsThis SD-OCT staging system describes the sequential in vivo morphologic changes after FTMH formation providing a novel imaging biomarker.