Our study demonstrates that β-zone PPA is associated with a faster rate of RNFL thinning as evaluated by OCT. These data add new information regarding the role of PPA in glaucoma progression and provide additional support for an association between PPA and glaucoma progression.
In the present study, the presence and the enlargement of PPA, as assessed by an increase in PDR, was associated with a faster rate of RNFL thinning. These data are consistent with previous findings.
4,5,9,10,13,14 Association between the presence of PPA and glaucoma progression have been demonstrated in ocular hypertension
10 and open angle glaucoma.
4,5,9 In addition, Uchida et al.
13 and Budde and Jonas
14 demonstrated the association of PPA enlargement and glaucoma progression.
However, the present study found no association between the initial PDR and the rate of OCT RNFL thinning. This finding differs from that of previous studies where glaucoma progression was associated with initial PPA size or PDR.
2 –4,9,30 Although the discrepancy may be attributable to factors including the different study populations with respect to ethnicity, type of glaucoma, differing definitions of PPA and the methods of measuring its area, and length of follow-up, it is notable that our study excluded patients with large PPA, which could affect the scan path of OCT. This exclusion should have eliminated the effect derived from very large PPA, thereby leading to a false-negative association. Indeed, both initial and final PDR values in our study (0.47 ± 0.30 and 0.51 ± 0.32, respectively) are smaller than those reported by Uchida et al.
13 (0.95 ± 0.40 and 1.12 ± 0.44, respectively).
It is notable that this result suggests that the presence of β-zone PPA might be a more important marker for glaucoma progression than the size of β-zone PPA. This is consistent with findings reported in the study by Teng et al.,
4 where the presence of β-zone PPA was a stronger predictor of future visual field progression than the size of β-zone PPA (hazard ratio, 2.27 vs. 1.03, respectively). Once β-zone PPA has developed, it is possible that the ensuing, continued insult to optic disc results in a greater susceptibility to progression and thus the presence of β-zone PPA is relatively more important than its size.
The rate of thinning at 7 o'clock and inferior quadrant were the only parameters that showed statistical significance. This result is in agreement with that of previous studies that 7 o'clock was the most frequent location that showed progression in RNFL thickness by stratus OCT, and that inferior average thickness measured by stratus OCT had the best performance to discriminate progressors from nonprogressors.
18,19 Meanwhile, the group difference in the rate of RNFL thickness change was not significant at nasal sectors (from 1 to 4 o'clock) and temporal sector (9 o'clock). This result accords with the observation that glaucoma patients retain their temporal or central visual field until the end stage of the disease.
31
In the present study, no IOP-related factors, including baseline IOP, mean follow-up IOP, and the fluctuation of IOP, were associated with a faster rate of RNFL thinning. The absence of such associations had been reported in several studies. In the study reported by Prata et al.,
32 the baseline IOP and the amount of IOP reduction were not risk factors for a faster rate of visual field loss after disc hemorrhage. In the study reported by Sung et al.,
33 none of the IOP-related parameters including baseline IOP, mean 24-hour admission value, follow-up average, or follow-up IOP fluctuation, was associated with visual field progression. However, these data including ours are in contrast with data from many previous studies,
34 –41 where an association between IOP and glaucoma progression was found. The discrepancy between studies on the effect of IOP on glaucoma progression may be explained by variations in patient populations under study and IOP levels seen during follow-up. The majority (87.6%) of our study patients had normal-tension glaucoma and all our patients were medically or surgically treated and maintained a relatively low mean follow-up IOP of 12.4 mm Hg. We believe that lowering of IOP is important to slow glaucoma progression. However, lowering IOP may not be equally effective in each individual glaucoma patient. Although it is evident that IOP is one of the strong risk factors for glaucoma progression, it may be possible that the absolute IOP level may be less important for the rate of progressive RNFL thinning in normotensive eyes, since low IOP could still be above the threshold of injury for individual optic nerve head tissue.
42
The baseline RNFL thickness was not related with a faster rate of RNFL loss in our study. Although it is generally acknowledged that baseline disease severity is related to further glaucoma progression, such observations are based on visual field analysis and may not be correct in all circumstances. For example, Leung et al.
18 reported that a higher baseline RNFL measurement was associated with an increased rate of RNFL reduction. This finding is in agreement with the curvilinear structure–function relationship observed in previous cross-sectional studies, suggesting that progression as measured by a decrease in RNFL thickness is more noticeable than is progression assessed by visual field measurements in patients with early-stage glaucoma, whereas the reverse is true when the disease is more advanced.
43,44 Thus, the relationship between baseline status and rate of progression may vary, depending on the stage of disease in enrolled patients and the method used to evaluate progressive change.
Studies have shown that disc hemorrhage is associated with PPA.
45,46 Because disc hemorrhage is a known significant risk factor for glaucoma progression, it is possible that the association of PPA with RNFL progression shown in the present study was mediated by more frequent disc hemorrhage in the PPA group. Due to the retrospective study design, however, the accurate frequency of disc hemorrhage and, thus, the influence of disc hemorrhage could not be evaluated. A prospective, longitudinal study is needed to address the influence of disc hemorrhage on glaucoma progression in eyes with PPA.
Although our data support the previous findings that determined the PPA as a risk factor for glaucoma progression, the result of the present study also validates the usefulness of trend-based approach of OCT RNFL thickness to monitor glaucoma progression. Our data show that OCT-based trend analysis is able to discriminate the eyes where the disease progresses faster, being associated with known risk factors for faster progression.
The MD was marginally significant between the groups at the end of the follow-up, whereas they were comparable at baseline. This finding indirectly suggests that the rate of visual field progression was faster in eyes with β-zone PPA, which is consistent with results reported in the study by Teng et al.
4 They reported a significantly faster rate of visual field progression in eyes with β-zone PPA than that in eyes without β-zone PPA. Taken together, both structural and functional evaluations indicate that β-zone PPA is a risk factor for faster glaucoma progression. However, the coexistence of the structural and functional progression may not be observed when evaluated in other study populations with different stages of disease because the change is often dependent on the stage of disease.
The present study has several limitations. First, we did not measure the PPA size in absolute units. Because of the retrospective study design, Heidelberg retina tomographic images were not available in many patients. Further, the patients did not receive keratometric readings and axial length measurement at each occasion of disc photography. Thus, it was not possible to correct the magnification factor in many patients. Nonetheless, we have shown that the increase in PDR is associated with structural glaucoma progression. Because optic disc size most likely is not changing, it is reasonable to consider that the change in PDR is derived from the increase of PPA. Thus, the result of our study may be interpreted to support earlier studies that demonstrated the association between the increase in PPA size and glaucoma progression. Second, patients were scanned using the same diameter scan ring without consideration of their disc size. This may affect the outcome because the RNFL thickness measurement can be affected by the disc size.
47 –49 However, we measured the rate of change based on the measurement on the same location as closely as possible; thus, the effect of using the same diameter scan ring should be much less than when the measurement of RNFL thickness is used for diagnostic purposes, which is often the case in clinical practice.
In conclusion, the presence and enlargement of β-zone PPA were significantly associated with the rate of progressive RNFL thinning as measured by OCT. Detailed examination of PPA in glaucoma may enable the clinician to obtain clinically relevant information about the possibility of future glaucoma progression.
Supported, in part, by a grant from the Seoul National University Bundang Hospital Research Fund.
Disclosure:
E.J. Lee, None;
T.-W. Kim, None;
R.N. Weinreb, Carl Zeiss Meditec (C, R);
K.H. Park, None;
S.H. Kim, None;
D.M. Kim, None