The papillomacular bundle (PMB) area is an important anatomical site associated with central vision. As preventive medicine and health screening examinations are now becoming commonplace, the incidental detection of papillomacular bundle defect (PMBD) on fundus photography has been increasing. However, clinical significance of incidental PMBD has not been well documented to date. Thus, through long-term and longitudinal observation, we aimed to investigate the risk factors for the development and progression of PMBD and its predictive role associated with systemic diseases and glaucoma. This longitudinal study included subjects who had undergone standardized health screening. We retrospectively reviewed patients for whom PMBD had been detected in fundus photography and followed up for more than 5 years. For a comparative analysis, non-PMBD groups of age- and gender-matched healthy controls were selected. A total of about 67,000 fundus photographs were analyzed for 8.0 years, and 587 PMBD eyes were found. Among them, 234 eyes of 234 patients who had had fundus photographs taken for more than 5 years were finally included. A total of 216 eyes (92.3%) did not progress during the 8.1 ± 2.7 years, whereas 18 eyes (7.7%) showed progression at 7.6 ± 2.9 years after initial detection. A multivariate logistic regression analysis using 224 non-PMBD healthy controls revealed low body mass index (BMI < 20 kg/m2), systemic hypertension, and sclerotic changes of retinal artery as the significant risk factors for the development of PMBD. Regarding PMBD progression, low BMI, concomitant retinal nerve fiber layer defect (RNFLD) at non-PMB sites, optic disc hemorrhage, and higher vertical cup/disc ratio were individual significant risk factors. PMBD is associated with ischemic effects. Although the majority of PMBD do not progress, some of cases are associated with glaucomatous damage in a long-term way. PMBD might be a personalized indicator representing ischemia-associated diseases and a predictive factor for diagnosis and preventive management of glaucoma.