BACKGROUND: To investigate and quantify the impact of intracranial lesions at different locations within the visual pathway on the ganglion cell layer-inner plexiform layer (GCL-IPL) complex and the retinal nerve fiber layer (RNFL). METHODS: Patients with intracranial lesions affecting the optic chiasm (Group I) or the optic tract and/or lateral geniculate nucleus (Group II) were included. All patients received kinetic visual field assessment and underwent spectral domain optical coherence tomography. Peripapillary and papillomacular bundle (PMB) RNFL and macular GCL-IPL thickness in 4 perifoveal areas were measured and compared with normal values derived from 52 age-matched healthy control subjects. Z-scores for each parameter of every patient were calculated and compared with the normative data. Z-scores less than -2.0 (e.g., -2.5) were considered as being statistically significant. RESULTS: Twenty-two patients (Group I and II: 13 and 9, respectively) were included. Ten of 13 patients in Group I showed significant binasal GCL-IPL thinning, with associated temporal sector thinning in 8 patients. In Group II, all 9 patients showed significant reduction of the GCL-IPL corresponding to the homonymous visual field defect, but only 4 demonstrated RNFL thinning. Contralateral RNFL thinning within the PMB clinically similar to bow-tie atrophy was evident in all patients in Group II. GCL-IPL and RNFL thinning varied in severity from mild (isolated PMB RNFL thickness reduction) to severe (bilateral asymmetrical reduction of PMB RNFL associated with asymmetric, predominantly nasal reduction of GCL-IPL) in Group I. CONCLUSION: Clinical abnormalities in patients with visual pathway lesions are more likely to demonstrate abnormalities of GCL-IPL than global peripapillary RNFL thickness. However, PMB thickness measurement appears to be a valuable tool to detect abnormalities of the anterior visual pathways. If peripapillary RNFL measurements are performed in such patients, PMB thickness should be considered the most useful quantitative parameter.