PURPOSE:To investigate whether vessel density assessed by optical coherence tomography angiography (OCT-A) is reduced in glaucomatous eyes with focal lamina cribrosa (LC) defects. DESIGN:Cross-sectional, case-control study. PARTICIPANTS:A total of 82 patients with primary open-angle glaucoma (POAG) from the Diagnostic Innovations in Glaucoma Study (DIGS) with and without focal LC defects (41 eyes of 41 patients in each group) matched by severity of visual field (VF) damage. METHODS:Optical coherence tomography (OCT) angiography-derived circumpapillary vessel density (cpVD) was calculated as the percentage area occupied by vessels in the measured region extracted from the retinal nerve fiber layer (RNFL) in a 750-μm-wide elliptical annulus around the disc. Focal LC defects were detected using swept-source OCT images. MAIN OUTCOME MEASURES:Comparison of global and sectoral (eight 45-degree sectors) cpVDs and circumpapillary RNFL (cpRNFL) thicknesses in eyes with and without LC defects. RESULTS:Age, global, and sectoral cpRNFL thicknesses, VF mean deviation (MD) and pattern standard deviation, presence of optic disc hemorrhage, and mean ocular perfusion pressure did not differ between patients with and without LC defects (P > 0.05 for all comparisons). Mean cpVDs of eyes with LC defects were significantly lower than in eyes without a defect globally (52.9%±5.6% vs. 56.8%±7.7%; P = 0.013) and in the inferotemporal (IT) (49.5%±10.3% vs. 56.8%±12.2%; P = 0.004), superotemporal (ST) (54.3%±8.8% vs. 58.8%±9.6%; P = 0.030), and inferonasal (IN) (52.4%±9.0% vs. 57.6%±9.1%; P = 0.009) sectors. Eyes with LC defects in the IT sector (n = 33) had significantly lower cpVDs than eyes without a defect in the corresponding IT and IN sectors (P < 0.05 for all). Eyes with LC defects in the ST sector (n = 19) had lower cpVDs in the ST, IT, and IN sectors (P < 0.05 for all). CONCLUSIONS:In eyes with similar severity of glaucoma, OCT-A-measured vessel density was significantly lower in POAG eyes with focal LC defects than in eyes without an LC defect. Moreover, reduction of vessel density was spatially correlated with the location of the LC defect.