Normal-tension glaucoma (NTG) is a chronic progressive optic neuropathy. It is defined as a condition of cupping of the optic disc and a visual field loss resembling that seen in other forms of chronic glaucoma but in which the untreated intraocular pressure (IOP) value is less than 22 mm Hg with open iridocorneal angle, and there is no obvious or apparent cause for these changes.1 The diagnosis of NTG is usually established by exclusion of other optic neuropathies.1–7 Whether or not the IOP and central corneal thickness (CCT) are correlated with disease severity is a controversial issue.8–12 CCT is usually not considered in defining NTG, although past studies showed that NTG patients have lower CCT measurements.13–15 NTG represents a subgroup of open-angle glaucoma with measured, untreated IOP in the statistically normal range. It is unclear whether this artificial clinical subdivision has any scientific validity with respect to disease pathophysiology or implications for treatment. It is widely believed that IOP plays a role in the pathogenesis of NTG.16–19
The purposes of this study were to determine the value of routinely evaluating CCT in patients with NTG and to evaluate the correlation between baseline IOP and CCT measurements and disease severity.
MATERIALS AND METHODS
This study was approved by the local institutional review board committee. Between 2002 and 2006, 68 patients were newly diagnosed as having bilateral NTG in our outpatient clinic. NTG was diagnosed according to the glaucomatous visual fields loss, glaucomatous optic disc cupping with apparent nerve fiber layer loss in the optic nerve head rim, and an IOP below 22 mm Hg on diurnal curve measurements. Diurnal IOP curve measurements were performed 6 times within 24 hours (08:00, 10:00, 12:00, 14:00, 16:00, and 20:00 h). All patients underwent visual field tests using the white-on-white full threshold or the Fastpac Humphrey 24-2 program.
All patients were evaluated by a neuroophthalmologist who conducted a comprehensive neurologic evaluation and neuroimaging in suspected cases of other optic neuropathies.
The patients were divided into 3 groups according to the severity of disease (mild, moderate, or severe visual fields defects) derived from the mean deviation (MD), pattern SD, and advanced glaucoma intervention score results. All patients performed at least 2 consecutive visual field tests to evaluate severity. For visual field reliability, false positive or false negative errors and fixation losses above 25% were not included. Global indices (MD and corrected pattern SD) were averaged from the 2 baseline fields. Criteria for a visual field abnormality were the presence of at least 3 contiguous points depressed >8 dB or 2 contiguous points depressed >10 dB. The location of the defect had to be consistent between baseline fields, and glaucomatous optic disc damage had to be consistent with the visual field abnormality. CCT measurements were performed using the ultrasonic AccuPachV (Accutome) with 3 consecutive measurements. The mean CCT, the mean maximal IOP, and the mean decrease in IOP after treatment were calculated, and the correlation between them and disease severity were determined.
The 3 groups of patients were compared for selected clinical parameters (pachymetry, maximal baseline IOP, IOP after treatment, and the IOP change after treatment) by a one-way analysis of variance. The Gabriel and the Games-Howell multiple comparison tests were employed to determine significant differences between pairs of groups. This analysis was carried out separately for each eye. The level of significance was set at 0.05 and the SPSS for windows software, version 14.0 (Chicago, IL) was used for the analysis.
Thirty-three females and 35 males were newly diagnosed as having NTG in our clinic between 2002 and 2006 (Table 1). The mean follow-up was 4.64 years. They all had NTG in both eyes but with different severity in each eye. The correlations between the 3 stages of the disease and pachymetry, maximal baseline IOP, IOP after treatment, and the IOP change after treatment are presented in Tables 2 and 3. Corneal thickness was normal in both eyes in the cases of mild NTG [548.58 (504 to 600) μm in the right eye (RE) and 549 (500 to 617) μm in the left eye (LE)], it was low in the RE but normal in the LE [522 (480 to 590) μm and 544.80(500 to 585) μm] in moderate disease, and it was low in both eyes [518.27(480 to 550) μm and 521(490 to 554) μm] in severe disease (P=0.007).
The mean maximal IOP without treatment was not significantly different at various stages of the disease in both eyes, indicating that this parameter was not useful for predicting disease severity. The IOP after treatment was lower in the more severe cases [13.44 (9 to 20) mm Hg, 12.22 (8 to 15) mm Hg, and 11.63 (7 to 17) mm Hg in mild, moderate, and severe disease in the RE; and 13.29 (8 to 16) mm Hg, 12.60 (8 to 21) mm Hg, and 12.32 (8 to 17) mm Hg in the LE, respectively] (P=0.009).
One of the aims of conducting this prospective study was to determine the value of routine CCT measurement as part of the diagnostic workup for suspected NTG. The Ocular Hypertension Treatment Study revealed that CCT was an important risk factor for progression from ocular hypertension to primary open-angle glaucoma.20 Multivariate analysis showed that its effect in the Ocular Hypertension Treatment Study was independent of IOP, also a risk factor for progression.21 Whether the effect of CCT is exerted through its influence on IOP measurement or through a truly independent expression of risk possibly based on biomechanical characteristics of ocular tissues, or both, remains a controversial issue.22
Some studies reported that patients with NTG had considerably thinner CCT values than those of patients with primary open-angle glaucoma or controls,8,9 whereas others10,11 did not find any difference in CCT measurements of patients with NTG compared with other types of glaucoma. Low CCT measurements, however, may underestimate the real IOP measurement.23
We did not consider CCT in defining NTG because NTG study and the Low-pressure Glaucoma Treatment Study did not include it in their diagnosis.11 In any case none of our patients had borderline IOP with CCT range below 520 μm.
In this study, the pretreatment IOPs did not correlate with the severity of visual field loss. This finding contradicts that of the report by the Collaborative Normal-Tension Glaucoma Study Group in which IOP was shown as being higher in cases of more severe NTG.9 In contrast, a recent publication by Greenfield et al24 showed no correlation between IOP and severity of visual field in NTG patients, results which are similar to ours. The IOP levels after treatment in our study were lower in the more severe cases in both eyes of our study patients. We presume that these differences represent the implementation of a more aggressive treatment protocol for patients in moderate and severe disease stages.
When we correlated CCT with disease severity, we found that the glaucomatous visual field loss was worse in the thinner corneas than in the thicker ones. This means that patients with thinner corneas and NTG require more aggressive treatment to stop glaucomatous deterioration. We also found that the mean CCT measurement was within average limits, that is, 534 μm in the RE and 540 μm in the LE, in agreement with Krupin et al's10,11 figure of 543 μm, but in contrast to other studies in the literature that assumed the CCT to be thinner in NTG patients.12–14 Hong et al25 found that when severe thin CCT is present in patients with NTG, the eye is at greater risk for progression of visual field loss. These results are similar to ours. Sullivan-Mee et al26 found that in eyes characterized by statistically normal IOP a significant relationship between CCT and the presence, but not severity, of glaucomatous visual field loss. Herndon et al27 found that a lower CCT was significantly associated with a worsened Advanced Glaucoma Intervention Study score, worsened MD of visual field, increased vertical and horizontal cup-disc ratios, and increased number of glaucoma medications, but they studied high-pressure glaucoma patients whereas our patients had NTG.
In conclusion, we recognize that the relatively small study population and the retrospective view of this study precludes our arriving at firm conclusions. On the basis of the results of our analyses, we suggest that routine CCT should be performed in every NTG patient. We recommend that patients with low CCTs should be given more aggressive treatment with the intent to halt disease progression.
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