PURPOSE: To describe the association of unilateral peripapillary myelinated retinal nerve fibers with myopia, strabismus, and amblyopia and to propose a possible pathologic mechanism. METHODS: Four patients who have the findings associated with unilateral peripapillary myelinated nerve fibers are described and reviewed. RESULT: All patients had poor visual outcomes despite treatment with full cycloplegic refraction and appropriate patching. CONCLUSIONS: Although the origin of this association is unknown, we believe that peripapillary myelinated nerve fibers in a unilateral myopic eye may be secondary to an imbalance between the process of myelination and the formation of the lamina cribrosa. Good results have been reported with amblyopic therapy; however, it is our experience that these patients are somewhat refractory to amblyopia therapy.