Optic Nerve Head Cotton Wool Spots Mimicking Inflammatory Optic Neuropathy in Central Retinal Vein Occlusion.

Central retinal vein occlusion (CRVO) typically presents with optic disc edema, venous dilation, and widespread retinal hemorrhages; however, atypical optic nerve head findings can mimic neuro-inflammatory or infiltrative disease, posing a diagnostic challenge. We report a 67-year-old woman with diabetes mellitus, rheumatoid arthritis, hypertension, and hyperlipidemia who presented for routine evaluation without visual symptoms and was found to have non-proliferative diabetic retinopathy bilaterally and clinical signs of non-ischemic CRVO in the left eye, including optic disc edema, hyperemia, and intraretinal hemorrhages. Optical coherence tomography (OCT) demonstrated mild macular thickening, and fluorescein angiography (FA) showed scattered hyperfluorescent foci with minimal leakage. Two months after intravitreal faricimab injection, macular edema resolved and visual acuity improved; however, as disc edema subsided, new large whitish nodular lesions emerged on the optic nerve head inferiorly, nasally, and superiorly, corresponding to hyperreflective deposits on OCT. Given the atypical appearance, brain and orbits MRI with contrast, lumbar puncture, and infectious and inflammatory laboratory testing were performed, all of which were unremarkable, with no evidence of infiltrative, demyelinating, or vasculitic disease. Repeat FA revealed no vessel wall staining or leakage to suggest retinal vasculitis. The nodular optic nerve lesions were ultimately determined to be prominent cotton wool spots (CWS) associated with CRVO, presenting in an unusual peripapillary distribution that spared the maculopapillary bundle, consistent with localized inner retinal ischemia and disruption of axoplasmic transport. The lesions resolved over several months without development of optic atrophy or collateral vessels, and final visual acuity returned to 20/20 with normal visual fields. This case highlights that large CWS on the optic nerve head in non-ischemic CRVO can closely mimic neuro-inflammatory or infiltrative processes and that multimodal imaging combined with multidisciplinary evaluation is essential to avoid misdiagnosis and unnecessary treatment.