Journal of Glaucoma:
Corneal Thickness Measurements in Normal-tension Glaucoma Workups: Is It Worth the Effort?
Kurtz, Shimon MD; Haber, Inbal MD; Kesler, Anat MD
Department of Ophthalmology, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Reprints: Shimon Kurtz, MD, Department of Ophthalmology, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, 6 Weizman Street, Tel Aviv 64239, Israel (e-mail: firstname.lastname@example.org).
Received for publication October 7, 2008; accepted February 24, 2009
Purpose: To correlate central corneal thickness (CCT) and intraocular pressure (IOP) with disease severity in normal-tension glaucoma (NTG) patients.
Methods: We conducted a retrospective review of all patients diagnosed with NTG in our institution between 2002 and 2006. NTG was diagnosed according to the glaucomatous visual fields loss, glaucomatous optic disc cupping, and an IOP <22 mm Hg on diurnal curve measurements. Mean CCT and IOP values before and after treatment were also evaluated. Patients were divided into 3 groups according to advanced glaucoma intervention score (mild, moderate, and severe visual field defects).
Results: A total of 33 females and 35 males with bilateral NTG were enrolled. The mean follow-up was 4.6 years. CCT was inversely correlated with glaucoma severity. CCT was normal in both eyes in mild disease, thin in the right eye (RE) and normal in the left eye (LE) in moderate disease, and low in both eyes in severe disease. Initial bilateral mean maximal IOP was similar at all disease stages and became lower after treatment in parallel to disease severity: 13.44, 12.22, and 11.63 mm Hg in the RE and 13.29, 12.60, and 12.32 mm Hg in the LE, respectively. There was no statistical difference in disease severity between the RE and LE.
Conclusions: CCT correlated with disease severity: the more advanced the disease, the thinner the cornea. Initial maximal IOP did not predict disease severity, but it was lower in the more severe cases after treatment, possibly representing a more aggressive treatment protocol.
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.
1. Werner EB. Normal tension glaucoma. In: Ritch R, Shields MB, Krupin T, eds. The Glaucomas. 2nd ed. St Louis: Mosby; 1996:769–797.
2. Wilensky JT, Gieser DK. Low-tension glaucoma. In: Weinstein GW, ed. Open-angle Glaucoma. Churchill Livingstone: New York; 1986:49–60.
3. Epstein DL. Low tension glaucoma. In: Epstein DL, Allingham RR, Schuman JS, eds. Chandler and Grant's Glaucoma. 4th ed. Baltimore: Williams and Wilkins; 1997:199–211.
4. Gutman I, Melamed S, Ashkenazi I, et al. Optic nerve compression by carotid arteries in low-tension glaucoma. Graefes Arch Clin Exp Ophthalmol. 1993;231:711–717.
5. Panek WC, Hepler RS. Low-tension glaucoma. In: Higginbotham EJ, Lee DA, eds. Management of Difficult Glaucomas. Boston: Blackwell Scientific Publications; 1994:205–214.
6. Grosskreutz C, Netland PA. Low-tension glaucoma. Int Ophthalmol Clin. 1994;34:173–185.
7. Hitchings RA. Low tension glaucoma—its place in modern glaucoma practice. Br J Ophthalmol. 1992;76:494–496.
8. Morad Y, Sharon E, Hefetz L, et al. Corneal thickness and curvature in normal-tension glaucoma. Am J Ophthalmol. 1998;125:164–168.
9. The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Collaborative Normal-Tension Glaucoma Study Group. Am J Ophthalmol. 1998;126:498–505.
10. Krupin T. Special considerations in low-tension glaucoma. Can J Ophthalmol. 2007;42:414–417.
11. Krupin T, Liebmann JM, Greenfield DS, et al, Low-Pressure Glaucoma Study Group. The Low-pressure Glaucoma Treatment Study (LoGTS) study design and baseline characteristics of enrolled patients. Ophthalmology. 2005;112:376–385.
12. Shah S, Chatterjee A, Mathai M, et al. Relationship between corneal thickness and measured intraocular pressure in a general ophthalmology clinic. Ophthalmology. 1999;106:2154–2160.
13. Morad Y, Sharon E, Hefetz L, et al. Corneal thickness and curvature in normal-tension glaucoma. Am J Ophthalmol. 1998;126:326–328.
14. Emara BY, Tingey DP, Probst LE, et al. Central corneal thickness in low-tension glaucoma. Can J Ophthalmol. 1999;34:319–324.
15. Rüfer F, Westphal S, Erb C. Comparison of central and peripheral corneal thicknesses between normal subjects and patients with primary open angle glaucoma, normal tension glaucoma and pseudoexfoliation glaucoma. Klin Monatsbl Augenheilkd. 2007;224:636–640.
16. Cartwright MJ, Anderson DR. Correlation of asymmetric damage with asymmetric intraocular pressure in normal-tension glaucoma (low-tension glaucoma). Arch Ophthalmol. 1988;106:888–900.
17. Crichton A, Drance SM, Douglas GR, et al. Unequal intraocular pressure and its relation to asymmetric visual field defects in low-tension glaucoma. Ophthalmology. 1989;96:1312–1314.
18. Haefliger IO, Hitchings RA. Relationship between asymmetry in visual field defects and intraocular pressure difference in an untreated normal (low) tension glaucoma population. Acta Ophthalmol. 1990;68:564–567.
19. Jonas JB, Gründler AE, Gonzales-Cortés J. Pressure-dependent neuroretinal rim loss in normal-pressure glaucoma. Am J Ophthalmol. 1998;125:137–144.
20. Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:714–720.
21. Brandt JD. Corneal thickness in glaucoma screening, diagnosis, and management. Curr Opin Ophthalmol. 2004;15:85–89.
22. Jonas JB, Holbach L. Central corneal thickness and thickness of the lamina cribrosa in human eyes. Invest Ophthalmol Vis Sci. 2005;46:1275–1279.
23. Shih CY, Graff Zivin JS, Trokel SL, et al. Clinical significance of central corneal thickness in the management of glaucoma. Arch Ophthalmol. 2004;122:1270–1275.
24. Greenfield DS, Liebman JM, Ritch R, et al, Low Pressure Glaucoma Study Group. Visual fields and intraocular pressure asymmetry in the low pressure glaucoma treatment study. Ophthalmology. 2007;114:460–465.
25. Hong S, Yun Kim C, Seong G, et al. Central corneal thickness and visual field progression in patients with chronic primary angle closure glaucoma with low intraocular pressure. Am J Ophthalmology. 2007;143:362–363.
26. Sullivan-Mee M, Halverson KD, Saxon MC, et al. Central corneal thickness and normal tension glaucoma: a cross-sectional study. Optometry. 2006;77:134–140.
27. Herndon LW, Weizwe JS, Stinnett SS. Central corneal thickness as a risk factor for advanced glaucoma damage. Arch Ophthalmol. 2004;122:17–21.
intraocular pressure; glaucoma; corneal thickness
© 2010 Lippincott Williams & Wilkins, Inc.