Peripapillary atrophy has always been considered as a possible risk factors related to glaucoma progression since found in the 20th century. Histological and radiographic evidences demonstrate that significant disappearance of photoreceptor cells and retinal pigment epithelial cells as well as occlusion of choroid capillary is the the main causes of formation of the beta zone.13 Studies have confirmed that the peripapillary atrophy zone has correspondence in space with the most obvious visual field damage. Jonas pointed out that in primary open-angle glaucoma, α zone is related to the relative scotoma of vision while the β zone is related to the absolute scotoma of vision.3 The area of the beta zone will change with the development of optic nerve damage in glaucoma, such as loss of disc edge, decrease of the diameter of retinal vessels, retinal nerve fiber layer defect, fundus hemorrhage and degree of visual field defect.5.14 The probability of future optic nerve damage and visual field defect of the suffering eyes with the beta zone at the very beginning was almost 3 times that of the eyes without the beta zone, and glaucoma of the patients with the beta zone progressed faster.4 Therefore, existence and development of the beta zone is an important parameter to identify glaucoma or the development of nervous lesion in glaucoma, and study of the beta zone may contribute to detection and diagnosis of early glaucoma and prediction of glaucoma development2.3. The reproducibility of the discrimination of alpha zone was poor, and the specificity and sensitivity of using alpha zone to identify the normal and glaucoma patients was low, so only the beta zone was selected as the research target in this study. At present, direct ophthalmoscope, indirect ophthalmoscope, slit lamp with pre-set lens and fundus stereoscopic photography are commonly used to observe the beta zone. These detection methods are convenient and fast, but with poor reliability and accuracy. In recent years, along with the enhancement of computer image processing technology, researchers can take advantage of the computer image processing softwares, such as photoshop and Image J to outline the boundary of optic disc and peripapillary atrophy zone as well as the angle and line o that need to be measured. Then, quantitative measurement of these parameters can be more accurate to study the morphology of peripapillary atrophy zone and the results are more credible.15.16 The population prevalence of the beta zone was 15–20% according to a report.17 It was easy to appear in the temporal region with the largest atrophy area, followed by the temporal inferior region and temporal superior region, and at least the nasal region with the minimal atrophy area. The population prevalence of the beta zone was 20.95% according to the Beijing Eye Study 2001,12 and the position and size of peripapillary atrophy zone, related to age, refractive error, optic disc area and best corrected visual acuity, was basically consistent with the research results from other population-based studies. Five years later, Beijing Eye Study evaluated beta zone again in 2006 and found that the progress rate of beta zone was 8.2 ± 0.5%, and age, hypertension, high myopia, corneal thickness and glaucoma were the related factors. 8
In this study, we found that the population prevalence of beta zone was 39.9%, which was a significant increase compared to the past prevalence study and the Beijing Eye Study in 2001. This may be due to the following reasons. First, the age of Beijing Eye Study population was older as a whole (over 50 in 2011), and this number increased significantly because the occurrence and development of the beta zone have obvious relationship with age. Second, the previous studies have determined beta zone only by the subjective judgment of an ophthalmologist, so it was hard to ascertain the beta zone when it was small, atypical, or the refractive media was not clear. In this study, SD-OCT with enhanced depth imaging was used to evaluate the fundus for the first time. Clinical and scientific research workers can observe the fault structures of peripapillary retina and choroid better, so they can have a more clear judgment and positioning of beta zone to make the results more reliable and credible. In this study, the beta zone of all the images was further evaluated by comparing with SD-OCT images when the digital photos cannot be determined by human or questioned. It can be speculated that former researchers were likely to ignore or mistaken part of the beta zone for alpha zone, resulting in the previous lower population prevalence of the beta zone.
The distribution of the beta zone both in the present and previous research was consistent, namely easy to appear in the temporal region with the largest atrophy area, followed by the temporal inferior region and temporal superior region, and at least the nasal region with the minimal atrophy area. Jonas pointed out that the beta zone corresponds to the absolute scotoma of vision in primary open-angle glaucoma. 3 Subclinical process of very early glaucoma is about 14 to 20 years, and it may be difficult to find an early and slight optic cup enlargement and mild and diffuse nerve fiber layer defect. But the progressive changes of peripapillary atrophy zone may occur before the clinical visible change of the optic disc or vision damage, and its sensitivity was 49% and specificity was 90% according to a study.18 Sullivan-Mee found that in POAG patients with the β zone, peripapillary choroid volume was reduced, and the beta zone may be a biological sign of POAG and it seems to be associated with vascular injury of glaucoma. 14 Tezel considered that high intraocular pressure and peripapillary atrophy zone increase the susceptibility of glaucomatic optic nerve damage for the following reasons:19 (1) Inadequate blood flow perfusion of this area can lead to an increased sensitivity of the optic nerve and peripapillary choroidal and retinal tissues to local damages. (2) Because the outer blood-retinal barrier was damaged in the peripapillary atrophy zone, the optic nerve fibers may be damaged due to their exposure to blood vessels, immunity, or other substances in the circulatory system when they pass through that area or they are in the extension section of peripapillary areas. This hypothesis explains the relationship between the peripapillary atrophy zone and glaucoma. The morphology of beta zone in different types of glaucoma is also different. If POAG patients had high myopia or is in the early stage, the area of beta zone will be larger, while the size of beta zone is relatively small in the normal-tension glaucoma and adolescent patients with POAG. It is relatively rare in patients with secondary glaucoma when compared with the patients with POAG.20 Therefore, it can be considered that the existence and development of the beta zone is an important parameter to diagnose and predict the progress of glaucoma or glaucomatic optic nerve damage. With the development of OCT technology, some scholars further use EDI-OCT to call the area which is closer to the optic papilla and lack of Bruch’s membrane as gamma zone, and this area was considered to be related with absence of glaucoma, age, and refractive status. 21 The combination of gamma zone can enhance the performance of the diagnosis and prediction of glaucoma with the beta zone. However, gamma zone is very difficult to distinguish without OCT.
In this study, the size of the beta zone has statistically significant association with increasing age, urban, cardiovascular disease history, axial length, myopic refractive error, retinal nerve fiber layer thickness, subfoveal choroidal thickness, optic disc size, age related macular degeneration. In Beijing Eye Study in 2001, the average age of the study population was 55. We found that age and the size of the beta zone were significantly related, and the area enlarged about 0.21 mm2 every 10 years. 12 In 2006, the population follow-up found that the progress rate of the size of the beta zone was 8.2 ± 0.5%. In 2011, the population was at an average age of 64 years, and the population prevalence of the beta zone was quite different from the previous study, so the data was not compared with that of 2001 and 2006. However, the population prevalence of the beta zone in this study was much higher than that of other population-based studies,17, 22 and age was probably one of the important influencing factors. Changes in histological structure may lead to decreased blood supply of the atrophy zone or blood-optic disc barrier dysfunction. Cardiovascular disease may cause eye ischemia and hypoxia which can lead to degenerate of RPE, at the same time RPE has the function of adjusting local blood circulation. So the larger atrophy area with less blood supply may cause enlargement of the atrophy zone easily. 23 Prior studies have in-depth research on beta zone in high myopia. They found that peripapillary scleral ring broadened and the beta zone enlarged obviously in patients with high myopia compared to those without high myopia. The optic disc area increased by 1.6%, the disc edge area increased by 1.4% and the beta zone area increased by 1.3% when myopia increased a diopter17. In our study, the beta zone area is related to axial length, myopic ametropia and optic pallia size, which is consistent with previous studies. Imamura believed that the continuous growth of axial length causes the mechanical stretching and thinning of choroid and RPE, which is one of the main causes of the atrophy of choroid and retinal pigment epithelium. 24 Therefore, the association of the existence of beta zone with myopia should be considered when the beta zone is used as the diagnosis indicator of glaucoma. However, the beta zone in presbyopia is relatively rare, so the beta zone found in presbyopia may predict an increased possibility of glaucoma. The histological character of the beta zone and age-related macular degeneration (AMD) is similar, both presenting retinal pigment epithelium layer degeneration and choroid capillary occlusion to cause the loss of retinal pigment epithelial cells. The results of Beijing Eye Study in 2001 demonstrated that the beta zone correlated with AMD in univariate analysis, but their correlation was not obvious in multivariate analysis. However, this study found that the beta zone was significantly related with no macular degeneration, and whether the existence of the beta zone would increase the risk of AMD is a meaningful research direction in the future. By the adjuvant of SD-OCT, SFCT was measured in this study for the first time, and we found that the beta zone and the SFCT could be relevant. The variation of the choroid thickness is very important for the accurate assessment of many diseases. The thickness of the choroid depends on choroidal blood perfusion, and the important factor of the occurrence of the beta zone is peripapillary poor choroidal perfusion. However, the change sequence of the beta zone and SFCT is not certain now, and research on their relationship has not been carried out yet. The causal relationship between them also needs long time follow-up and shorter follow-up interval to prove.
At present, most researches on the beta zone are around glaucoma. Certainly, the prevalence and the size of the beta zone of the patients with glaucomatic optic nerve injury are significantly greater than that of the normal eyes, and larger size of the beta-zone at baseline is the risk factor of the bata-zone expansion. 4 Changes in histological structure may lead to decreased blood supply of the atrophy zone or blood-optic disc barrier dysfunction. Larger atrophy area with less blood supply may cause enlargement of the atrophy zone easily. In the initial diagnosis of glaucoma, the disease progression was faster if there are beta zone in patients’ fundus, therefore, with the beta zone and its development is the important parameter of glaucoma. In our study, the presence and the area of the beta zone has statistically significant association with the glaucoma in univariate analysis, but the significant association does not exist in mulitiate analysis. The reason might be that the subjects were different, and most of previous studies were hospital-based studies. In the normal people, the glaucoma might not be the main cause of the beta zone changes.
There are still some insufficiencies of this study. The Beijing Eye Study 2011 is the third time follow up in the population, non-participation is the major concern. The response rate was 78.8%, which is reasonable, however, a selection bias may be caused by the differences between participants and nonparticipants. Participants cannot be taken an available fundus photographs for opacity of refracting media, which is also a limiting factor of this study. The measurement figures for peripapillary atrophy may be artificially underestimated because of it. Moreover, findings from our study cannot allow to directly drawing conclusions on cause-relationships. Strengths of our study are that SD-OCT with enhanced depth imaging was used for the first time in a population-based prevalence study, and maked the results more reliable and credible.