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To evaluate the natural history of myelinated retinal nerve fiber layer (MRNFL) through clinical features and enhanced depth imaging optical coherence tomography.This is a retrospective, noncomparative, case series of patients who underwent thorough clinical examination to document associated ocular and systemic features. Enhanced depth imaging optical coherence tomography was performed when MRNFL was located posteriorly and accessible to imaging.Seventy-two eyes of 62 patients had a total of 86 MRNFL lesions. Enhanced depth imaging optical coherence tomography (n = 42 eyes) showed that all lesions originated in the nerve fiber layer with preservation of the vascular structures. Mean thickness by enhanced depth imaging optical coherence tomography was 255 μm (median, 182 μm; range, 61–717 μm). Natural history was obtainable in 58 lesions with a mean follow-up duration of 57 months (median, 37 months; range, 2–253 months) with no significant change overall in largest basal diameter (2.5 vs. 2.5 mm; P = 0.361) or thickness (255 vs. 240 μm; P = 0.053). However, evidence of lesion change included growth in base only (≥0.5 mm) (3 of 58; 5%), growth in base (≥0.5 mm) and thickness (≥50 μm) (3 of 58; 5%), and reduction in base (≥0.5 mm) after plaque radiotherapy for choroidal melanoma (3 of 58; 5%).In general, MRNFL is a rare, benign retinal finding with a potential for growth in 10% of cases. This supports previous histopathological reports that MRNFL represents accumulation of both myelin and oligodendrocytes and could be an oligodendrocytic choristoma.