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To compare optical coherence tomography angiography (OCTA) measured macular vessel density and spectral domain optical coherence tomography (SDOCT) measured macular ganglion cell complex (GCC) thickness in primary open-angle glaucoma eyes with and without focal lamina cribrosa (LC) defects.In this cross-sectional, case-control study of patients with primary open-angle glaucoma, 46 eyes of 46 patients with LC defects and 54 eyes of 54 patients without observable LC defects were included. OCTA and SDOCT imaging were performed on the same day by the same operator. Perimetry and swept-source OCT testing used to identify LC defects were conducted within 6 months of OCTA and SDOCT testing. Global and local parafoveal vessel density and macular GCC thickness were compared between study groups.Glaucoma severity was similar between groups (SAP mean deviation=−5.63 and −4.64 dB for eyes with and without LC defects, respectively; P=0.40). Global and local measured parafoveal vessel density was similar between groups (all P≥0.11). GCC focal loss volume was higher in eyes with LC defects than eyes without LC defects (7.2% and 4.97%, respectively; P=0.03). In addition, GCC focal loss volume was topographically related to defect location in LC defect eyes.Although OCTA macular vessel density was not significantly different between eyes with and without LC defects, focal GCC loss in eyes with LC defects was different. This highlights the importance of not relying solely on vessel density measurements for determining macular changes for diagnosing and detecting glaucomatous progression.