Purpose: To evaluate ischemic changes in brain magnetic resonance images in patients with pseudoexfoliation syndrome (PXS) and pseudoexfoliation glaucoma (PXG) and compare them with age- and sex-matched control subjects. Methods: This case-control study involved 16 consecutive patients with PXS, 21 patients with PXG and 18 healthy age- and sex-matched control subjects. Each subject underwent a comprehensive ophthalmological examination. In all participants, an axial T-1-, T-2- and proton-density-weighted and coronal cerebral 1.5-tesla magnetic resonance imaging (MRI) scan was made. White matter hyperintensities (WMH) were considered present if these were hyperintense on both proton-density- and T-2-weighted images and not hypointense on T-1-weighted images. White matter lesions were classified into two parts as the subcortical and periventricular regions. We used a validated rating scale of subcortical WMH: 0 = absent, 1 = punctuate foci, 2 = beginning confluence of foci and 3 = large confluent areas. Periventricular white matter lesions were classified on a scale of 0 (no white matter lesions), 1 (pencil-thin periventricular lining), 2 (thick lining) or 3 (large confluent white matter lesions). Results: The proportions of persons with WMH were 93.7% for patients with PXS, 95.2% for patients with PXG and 55.5% for control subjects. The numbers of white matter lesions in patients with PXS and PXG were significantly greater than in the control subjects (p < 0.05). White matter lesions at subcortical locations in patients with PXG were significantly more frequent than in the control subjects (80.9 vs. 33.3%; p < 0.05). The proportion of patients with subcortical WMH was 56.2% in PXS; no significant difference was found in subcortical WMH between PXS and controls. The proportions of patients with periventricular WMH were 93% in PXS, 90.4% in PXG and 44.4% in controls. White matter lesions at periventricular locations in patients with PXG and PXS were significantly more frequent than in the control subjects (p < 0.05). The difference between the pseudoexfoliation groups and controls with regard to the size of periventricular and subcortical white matter lesions was statically significant (p < 0.05). When patients with PXS were compared with PXG patients, there was no statistically significant difference in the number, size and scale of white matter lesions. Conclusion: We found a significantly higher prevalence of MRI-defined WMH in patients with a clinical diagnosis of pseudoex-foliation with or without glaucoma versus control subjects. We think that the findings in this study may shed light on a possible link between ischemic brain lesions and pseudoexfoliation, which is not related with the presence of glaucomatous optic neuropathy. Further investigations are required to resolve the underlying associations.