The patient was a 73-year-old Japanese woman who had been suffering from visual loss and a history of floaters in the right eye from May 2012. The right eye had vitreous haze and retinal white foci in the peripheral fundus, the causes of which were unclear in a detailed examination. For further examination and treatment, she was referred to Jikei University Hospital and visited in June 2012. She was immunocompetent and had no underlying systemic diseases. On presentation, the best-corrected visual acuity (BCVA) was 0.02 OD and 1.2 OS. There was no relative afferent pupillary defect. The patient had no cells in the anterior chamber and diffuse vitreous cells with trace haze in the right eye. Funduscopic examination of the right eye showed a yellow submacular lesion at the fovea, in addition to vitreous haze and retinal foci scattered in the peripheral region. The left eye appeared normal. Spectral-domain optic coherence tomography (SD-OCT) revealed hyperreflective subretinal debris resembling vitelliform deposition above the retinal pigment epithelium (RPE) band. Fluorescein angiography (FA) imaging showed multiple hyperfluorescent lesions of various sizes in the peripheral region. Serologic test results, including those for antitoxoplasma IgG and IgM antibodies, angiotensin-converting enzyme, and viral antibodies such as herpes simplex virus, varicella zoster virus and cytomegalovirus, were within normal limits. Chest X-ray and magnetic resonance imaging were unremarkable. Vitreous haze slowly worsened within a few months. A 25-gauge pars plana vitrectomy was performed to improve visualization of the retinal lesions and for examination of causative microorganisms or PIOL. Vitreous cytology was class III and the cytokine analysis of vitreous fluid revealed increased IL-10 and an IL-10/IL-6 ratio >1, suggesting PIOL. Three months later, there were appearances of new multiple yellow-white sub-RPE infltrates in the peripheral fundus. At this time, SD-OCT still showed a hyperreflective material above the RPE band. PCR analysis of the anterior chamber fluid revealed IgH gene rearrangement, thus allowing a definitive diagnosis of PIOL. In a few months later, SD-OCT revealed hyperreflective bands and nodules above the RPE band with regression of the vitelliform debris. Finally, the patient decided to treat with intravitreal methotrexate injections (weekly 400 μg/100 mL for 6 weeks). The patient has survived with a total-follow up of 31 months, with no invlolvement of the central nervous system. The right eye has remained recurrence-free 24 months after the 20th intravitreal methotrexate injections. BCVA improved to 0.4 in the right eye.