Methods

Glaucoma patients aged 18 to 90 years with disc photographs at the time of or within 12 months of the study visit were consecutively enrolled in this prospective study. All patients seen over a 2-month period were screened for eligibility. Those who met the eligibility requirements and consented to the study were included. Glaucoma was defined by characteristic changes of the optic nerve with associated visual field changes. Exclusion criteria consisted of history of ocular surgery other than clear corneal phacoemulsification, myopia >6 diopters, contact lens use, and corneal abnormality precluding accurate tonometry or CH measurement. For patients who had undergone clear corneal phacoemulsification, the preoperative refractive error was used in assessing their eligibility. No type of glaucoma was excluded from the study.

To determine the presence of βPPA, 1 glaucoma specialist masked from clinical data reviewed all optic disc stereophotographs. Parapapillary atrophy was defined as an inner crescent of chorioretinal atrophy with visible sclera and choroidal vessels (βPPA) and an outer irregular area of hypopigmentation and hyperpigmentation (alpha-zone PPA). In this study, only the presence of βPPA in photographs was reported and used in the analyses. For photographs in which βPPA was present, the reviewer measured its area in clock-hours (1 to 12) using the same method previously described. Corneal hysteresis was measured using the Ocular Response Analyzer (ORA; Reichert, Inc, Buffalo, New York, USA) by an observer masked to the patient diagnosis and optic disc findings. This technique of CH measurement has been previously described. A good-quality reading was defined as one with a waveform score (WS) of >5. Three measurements were obtained for each eye and the best waveform as determined by the computer software was used for statistical analysis.

Results

We recruited 99 patients (mean age 67.6 ± 2.3 [SE] years). There were 45 men (45.5%) and 54 women (54.5%). One eye was eligible for inclusion in 33 subjects (33.3%), whereas both eyes were eligible in 66 (66.7%). Sixty-five patients (65.7%) had primary open-angle glaucoma (POAG), 10 (10.1%) normal-tension glaucoma (NTG), 8 (8.1%) exfoliative glaucoma (XFG), 8 (8.1%) chronic angle-closure glaucoma (CACG), 4 (4.0%) juvenile open-angle glaucoma (JOAG), 3 (3.0%) pigmentary glaucoma (PG), and 1 (1.0%) uveitic glaucoma.

When comparing patients with and without βPPA, univariate analysis ( Table 1 ) showed no statistically significant difference in CH between eyes with and without βPPA (8.72 ± 0.23 mm Hg vs 8.15 ± 0.27 mm Hg, P = .11). There were no differences in corneal resistance factor (CRF) (9.23 ± 0.37 mm Hg vs 9.64 ± 0.43 mm Hg, P = .47), CCT (550.0 ± 5.07 μm vs 537.5 ± 5.78 μm, P = .11), ORA wave score (8.63 ± 0.12 vs 8.41 ± 0.14, P = .23), age (68.2 ± 2.1 years vs 64.3 ± 2.5 years, P = .23), sex ( P = .40), GAT measurements (17.33 ± 0.70 mm Hg vs 17.52 ± 0.82 mm Hg, P = .86), or VFMD (−7.37 ± 0.97 dB vs −6.24 ± 1.12 dB, P = .45). Eyes with βPPA were more myopic (−1.49 ± 0.27 diopters vs −0.22 ± 0.31 diopters, P = .003). Moreover, multivariate analysis ( Table 2 ) adjusting for age, SE, VFMD, and wave score showed no significant difference in CH between eyes with and without βPPA (8.69 ± 0.24 mm Hg vs 8.19 ± 0.28 mm Hg, P = .38).

When comparing fellow eyes of patients with asymmetric βPPA, we found no significant difference in CH (8.97 ± 0.22 mm Hg vs 9.10 ± 0.22 mm Hg, P = .69). There was also no significant difference in CRF (8.77 ± 0.28 mm Hg vs 9.26 ± 0.28 mm Hg, P = .21), CCT (550.57 ± 5.71 μm vs 551.23 ± 5.71 μm, P = .93), GAT (15.97 ± 0.72 mm Hg vs 16.03 ± 0.72 mm Hg, P = .95), or SE (−0.82 ± 0.37 diopters vs −0.94 ± 0.37 diopters, P = .82). VFMD was worse in eyes with greater βPPA (−9.16 ± 1.16 dB vs −6.10 ± 1.16 dB, P = .07).

Results

We recruited 99 patients (mean age 67.6 ± 2.3 [SE] years). There were 45 men (45.5%) and 54 women (54.5%). One eye was eligible for inclusion in 33 subjects (33.3%), whereas both eyes were eligible in 66 (66.7%). Sixty-five patients (65.7%) had primary open-angle glaucoma (POAG), 10 (10.1%) normal-tension glaucoma (NTG), 8 (8.1%) exfoliative glaucoma (XFG), 8 (8.1%) chronic angle-closure glaucoma (CACG), 4 (4.0%) juvenile open-angle glaucoma (JOAG), 3 (3.0%) pigmentary glaucoma (PG), and 1 (1.0%) uveitic glaucoma.

When comparing patients with and without βPPA, univariate analysis ( Table 1 ) showed no statistically significant difference in CH between eyes with and without βPPA (8.72 ± 0.23 mm Hg vs 8.15 ± 0.27 mm Hg, P = .11). There were no differences in corneal resistance factor (CRF) (9.23 ± 0.37 mm Hg vs 9.64 ± 0.43 mm Hg, P = .47), CCT (550.0 ± 5.07 μm vs 537.5 ± 5.78 μm, P = .11), ORA wave score (8.63 ± 0.12 vs 8.41 ± 0.14, P = .23), age (68.2 ± 2.1 years vs 64.3 ± 2.5 years, P = .23), sex ( P = .40), GAT measurements (17.33 ± 0.70 mm Hg vs 17.52 ± 0.82 mm Hg, P = .86), or VFMD (−7.37 ± 0.97 dB vs −6.24 ± 1.12 dB, P = .45). Eyes with βPPA were more myopic (−1.49 ± 0.27 diopters vs −0.22 ± 0.31 diopters, P = .003). Moreover, multivariate analysis ( Table 2 ) adjusting for age, SE, VFMD, and wave score showed no significant difference in CH between eyes with and without βPPA (8.69 ± 0.24 mm Hg vs 8.19 ± 0.28 mm Hg, P = .38).

When comparing fellow eyes of patients with asymmetric βPPA, we found no significant difference in CH (8.97 ± 0.22 mm Hg vs 9.10 ± 0.22 mm Hg, P = .69). There was also no significant difference in CRF (8.77 ± 0.28 mm Hg vs 9.26 ± 0.28 mm Hg, P = .21), CCT (550.57 ± 5.71 μm vs 551.23 ± 5.71 μm, P = .93), GAT (15.97 ± 0.72 mm Hg vs 16.03 ± 0.72 mm Hg, P = .95), or SE (−0.82 ± 0.37 diopters vs −0.94 ± 0.37 diopters, P = .82). VFMD was worse in eyes with greater βPPA (−9.16 ± 1.16 dB vs −6.10 ± 1.16 dB, P = .07).

Discussion

The presence and extent of βPPA have been linked to the development and progression of glaucomatous optic neuropathy. Similarly, eyes with lower CH have worse VF damage and are more likely to progress. Based on the hypothesis that opposite ends of the sclera (cornea and optic nerve) may share structural similarities, we sought a relationship between βPPA and CH. We found no significant difference in CH between eyes with and without βPPA or between fellow eyes with asymmetric βPPA, even after adjusting for confounding variables.

Glaucoma is a multifactorial disease, and elevated IOP is the most important known risk factor. Many other potential risk factors have been identified. In patients with normal-tension glaucoma, in particular, risk factors related to ocular perfusion pressure have been reported. These include systemic hypertension, hypotension, diabetes mellitus, increased blood viscosity, and vasospasm. These may cause chronic or intermittent ischemia to the optic nerve head, thereby contributing to glaucomatous damage even at normal pressures. Autoimmune factors may also play a role in the development of glaucoma.

A number of studies have evaluated and characterized the appearance of the optic nerve head in glaucoma. Drance and associates divided glaucomatous discs into 4 categories (localized focal ischemic, myopic, senile sclerotic, and generalized enlargement of the optic disc cup). Furthermore, they found that certain risk factors were associated with different appearances of the optic disc. Patients with focal ischemic discs were more likely to be female and to have migraines, a vasospastic response to cold, and disc hemorrhages. Older age, hypertension, ischemic vascular disease, and the use of cardiovascular medication were associated with senile sclerotic discs. Generalized enlargement of the cup was seen only in patients with elevated IOP. Burgoyne and Downs have proposed that age-related changes in the optic nerve head complex predispose to glaucomatous damage. They hypothesized that optic nerve head biomechanics serve as the link between IOP and non-pressure-dependent factors. These biomechanical factors, including laminar and peripapillary scleral connective tissue geometry and material properties (strength, stiffness, rigidity, compliance, and nutrient diffusion capabilities) may explain the physiology of normal aging of the optic nerve head as well as susceptibility to various levels of IOP and the development of glaucomatous optic neuropathy.

It has also been hypothesized that biomechanical characteristics of the cornea may reflect those of the optic nerve complex. Lesk and associates suggested that thicker corneas are associated with a less compliant optic nerve head. Bochmann and associates found that glaucomatous eyes with an acquired pit of the optic nerve have a lower CH and hypothesized an association between CH and laminar biomechanics. Assuming a significant association between corneal biomechanical properties and optic nerve head compliance, one could imply that a lower CH could be a surrogate for increased deformability and susceptibility to glaucomatous damage of the optic nerve complex. If βPPA represents a structural weakness of the parapapillary sclera, then a lower CH may be found in patients with βPPA and in eyes with more βPPA when comparing asymmetric fellow eyes.

Also corroborating the aforementioned hypothesis, Wells and associates found an association between a higher CH and optic nerve deformation when IOP was artificially elevated in glaucomatous eyes. Conversely, Prata and associates found that a lower CH is associated with topographic changes in the optic nerve head following acute reduction of IOP. Sun and associates found that CH was significantly lower in patients with chronic primary angle-closure glaucoma and that the CH rose with reduction of IOP. These studies demonstrate the complex relationship among corneal biomechanical properties (including CH), IOP, and alterations of the optic nerve complex. We found no difference in IOP between eyes with and without βPPA or between fellow eyes with asymmetric βPPA.

We also found no difference in CH in eyes with and without βPPA, both with univariate analysis and with multivariate analysis correcting for potential confounding variables including age, SE, VFMD, and wave score. The lack of association between CH and βPPA is strengthened by the fact that there is no difference in CH in fellow eyes with asymmetric βPPA. This implies that there may not be a significant structural link between the 2 factors.

In conclusion, this study shows no difference in CH in eyes with and without βPPA or between fellow eyes with asymmetric βPPA. More study is needed to better understand the role that corneal and optic nerve head biomechanics play in the development and progression of glaucoma as well as the relationship between the two.