Health screening program revealed risk factors associated with development and progression of papillomacular bundle defect

Abstract

Background/aims: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Cardiovascular disease; Disease development and progression; Glaucoma; Health screening examination; Ischemia-associated diseases; Longitudinal study; Low body mass index; Ophthalmology; Papillomacular bundle defect; Personalized indicator; Predictive factors; Predictive preventive personalized medicine (PPPM/3PM); Preventive management; Program; Risk assessment; Risk factors; Screening; Systemic effects and characteristics.

Fig. 1

Definition of papillomacular bundle defect (PMBD). The red line is a straight line from the center of the optic disc to the foveal center and is termed the “reference line.” Draw a line (solid blue line) that runs perpendicular to the reference line and passes through the center of the optic disc. The dotted blue line is a 3.46-mm-diameter circle centered on the optic nerve head and including the reference line and vertical line. As a result, the hemisphere can be divided into six equal sectors (a~f sections). Among the six sectors, the central upper and lower sectors surrounding the reference line (c + d section) from −30 to +30° were defined as the PMB area. A retinal nerve fiber layer defect was considered to be PMBD (2 white arrows) when the proximal border of the nearest defect was located within “sector c or d”

Fig. 2

Determination of progression of papillomacular bundle defect (PMBD). Patients with PMBD were classified into “progressors” and “non-progressors” based on the following criteria. (A) deepening or (B) widening of PMBD. a Deepening of PMBD was defined as the presence of significant change overlapping with a pre-existing defect. b Widening of PMBD was defined as a significant change to the edge of a pre-existing defect

Fig. 3

Flow chart for enrollment and subgroup analysis

Fig. 4

Representative a non-progressor and b progressor cases in papillomacular bundle defect (PMBD) group. a A 49-year-old man with systemic hypertension and hyperlipidemia demonstrated cooper wire-like sclerosis on the retinal vessels in fundus photography (black arrow). A PMBD (white arrow) began to be observed with cotton wool spot (green arrow) in the right eye since 2005 and remained stationary for 14 years until 2019. b A 40-year-old female patient with no underlying disease initially had a suspicion of PMBD on her right eye (white arrow) in 2011, which continued to increase in size until 2017. During the follow-up, retinal nerve fiber layer defect developed with optic disc hemorrhage on the left eye (red arrow)

Fig. 5

Kaplan-Meier survival analysis of stationary papillomacular bundle defect (PMBD). The subgroups were stratified as a body mass index (BMI) < 20 or ≥ 20 kg/m², b presence or absence of optic disc hemorrhage, c concomitant retinal nerve fiber layer defect on ipsilateral eye, and d vertical cup to disc ratio ≥ 0.40 or < 0.40