Discussion
To our knowledge, this is the first study to describe the characteristics of β-PPA in patients with PACS. Our study showed that the occurrence rates of β-PPA were 48.80% and 44.40% in PACS and NPACS, respectively. Despite a similar occurrence rate, the size of β-PPA was different between the two groups. The average area of β-PPA in PACS was significantly larger than that in NPACS.
β-PPA can be commonly found in glaucomatous eyes, and normal eyes as well. However, It has been found that β-PPA occurs more often in glaucomatous eyes compared with normal eyes, significantly larger as well.15 Moreover, previous studies have underscored the pathogenic significance of β-PPA in POAG.14 20 Investigators pointed out that the formation of β-PPA may be a pathogenic mechanism in glaucomatous optic nerve damage.20 In addition, β-PPA plays an important role in the diagnosis and progression of POAG.21–23 A larger β-PPA area was associated with the diagnosis of POAG and contributed to distinguishing healthy eyes from eyes with POAG.24 Furthermore, increased β-PPA parameters, including area, angular extent, radial extent and margin regularity, have been reported to be associated with the progressions of POAG and glaucomatous visual field.16 25 However, the role of β-PPA is unclear in eyes with PACG, despite a few studies reporting the prevalence and characteristics of β-PPA in PACG.26
In contrast to POAG, the elevation of the IOP was the only cause of GON in PACG. Wang et al observed that parapapillary RPE folding or centrifugal sliding after an acute elevation of IOP.18 On the basis of this finding, they suggested that the presence and development of β-PPA, which was characterised by the loss of RPE cells, might be associated with the mechanical stress applied to the RPE layer on the parapapillary Bruch’s membrane due to increased IOP.27 The model used by Wang et al was a provocative test for PACG (the dark room prone provocative test), and it provides a good model to infer that the presence and development of β-PPA are associated with progression in PACG.
Our study showed that the area of β-PPA in eyes with PACS was significantly larger than that in eyes with NPACS after adjusting for age and the AL. PACS is the early stage of PACD, and in some cases, progresses to PAC/PACG. During the progression period, appositional angle closure or PAS may occur, which results in inconsistent or sustained increases in the IOP. The dark room prone provocative test simulates a kind of appositional angle closure in PACS, which is reversible and will generally reopen the angle after relaxation or medication.28 29 This might explain the large area of β-PPA in PACS due to appositional angle closure.
We further evaluated the factors associated with the presence and size of β-PPA in all participants and demonstrated that the presence of β-PPA was associated with older age and a larger disc area. A larger β-PPA area was associated with older age, a larger VCDR, a larger disc area and diagnosis of PACS, as well as several factors associated with β-PPA. Mataki et al’s study demonstrated that the presence of β-PPA was related to older age, myopic refraction, a greater disc area and lower IOP.30 Vianna et al found that the area of β-PPA was larger in eyes with POAG than in normal eyes.31 Several studies have reported that the area of β-PPA was also related to BCVA and glaucomatous optic nerve damage, which was, to some extent, similar to our study’s results.26 32 33
The finding that the presence and area of β-PPA are associated with older age could be explained by age-related degeneration.34 Panda-Jonas et al reported that approximately 0.3% of retinal photoreceptors and RPE cells are lost per year throughout one’s life and choriocapillary atrophy occurs.35 The positive correlation between the presence and area of β-PPA with a larger disc area might also be explained by the long perfusion distance.36 Previous studies assumed that the laminar and prelaminar regions of larger discs would be more vulnerable than other regions to localised hypoperfusion, which might cause degeneration of RPE and photoreceptors.36
The area of β-PPA was also positively correlated with the VCDR in our study, which was similar to the findings reported by Uhm et al and Jonas and Naumann.11 15 In those two studies, the area of β-PPA was correlated with the VCDR in normal and glaucomatous eyes.11 15 This study’s results, to some extent, indicated that β-PPA area increased positively with the tendency of optic disc cup enlargement, although damage due to glaucoma did not occur in participants with PACS. Therefore, in the future study, we will further investigate the differences in characteristics of β-PPA between eyes with PACS and PAC/PACG to see if any characteristic of β-PPA might be a possible predictor for the progression of PACD.
Our study has a few limitations. First, the study only enrolled patients with PACS and NPACS; the inclusion of β-PPA in patients with PAC/PACG may provide more information in a future study. Second, this study was a cross-sectional design; follow-up of the changes in β-PPA and the progression from PACS to PAC or PACG will offer strong evidence. Third, standard automated perimetry was not performed in all participants. So, there might be some possibility that PACG is being mistaken for PACS. However, IOP, readable fundus images and OCT examination were taken and all the GON or suspectable GON were excluded. Further follow-up investigations on the associations between β-PPA and GON in eyes are needed.