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Introduction
CCT and IOP Measurement
Central Corneal Thickness and Glaucoma Management
CCT and the Etiology of Glaucoma Risk
IOP Measurement after Refractive Surgery
Pachymetry
Conclusion
References

Slides

 Glaucoma

Central Corneal Thickness and Glaucoma

Mehdi Ghajarnia, MD

Introduction

Applanation tonometry has been the clinical gold standard for intraocular pressure (IOP) determination and the management of glaucoma for almost 50 years. Although Goldmann acknowledged the variable influence of central corneal thickness (CCT) on IOP determination by his applanation method,1 it is only recently that the role of CCT has resurfaced as a topic of interest and debate. Until several years ago, routine clinical practice had ignored the effect of CCT on IOP measurement; however, IOP has been central in the diagnosis of glaucoma and remains the only controllable parameter in glaucoma treatment. As such, an accurate assessment of IOP is critical. Two factors have contributed to the reemergence of this topic in ophthalmology: results of the Ocular Hypertension Study (OHTS) and the increasing popularity of corneal refractive surgery.

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CCT and IOP Measurement

Direct measurement of IOP through cannulation of the anterior chamber remains limited to experimental purposes, and currently all clinical means of measuring IOP are indirect and influenced by the cornea. Assuming an average corneal thickness of 500 microns, Goldmann and Schmit designed their tonometer based on the external force needed to flatten the central cornea to a minimum of area of applanation (3.06 mm). In their landmark article,1 they acknowledged the variable influence of corneal thickness and scleral rigidity on IOP measurement, but underestimated the degree of variability in CCT among human eyes. Comparing measurements with direct cannulation and those measured by applanation tonometry, Ehlers and colleagues2 demonstrated that the Goldmann tonometer’s most accurate reading was at a corneal thickness of 520 microns; they calculated that applanation tonometry overestimated (for thicker corneas) or underestimated (for thin corneas) true IOP by approximately 5 mm Hg for every 70 microns of deviation in corneal thickness. Later, Whitacre and colleagues3 used a Perkins tonometer and proposed that applanation tonometry was most accurate between 540 microns and 550 microns.

Other factors that can affect applanation tonometry include corneal elasticity and curvature and the presence of edema. Flatter corneas are associated with lower IOP readings by applanation tonometry,4 and corneal edema can underestimate the true IOP. Carbonic anhydrase inhibitors have been shown to cause a small and transient increase in CCT and, thus, may theoretically affect applanation readings.

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Central Corneal Thickness and Glaucoma Management

During the past decade, several cross-sectional studies demonstrated that mean CCT is greater in patients defined as having ocular hypertension compared with normal individuals and patients with glaucoma.5-7 The implication of these findings was that some patients classified as ocular hypertensive may have thicker corneas that result in an overestimation of their true IOP, and that they are actually at low risk for progression to glaucoma.

Conversely, many patients classified as normals or as having normal-tension glaucoma6,8 have thinner corneas that cause an underestimation of their true IOP and place them at higher risk for glaucoma or progression of glaucomatous vision loss. OHTS is a multicenter prospective study that sought to identify risk factors and evaluate early treatment among patients diagnosed with ocular hypertension; CCT measurement was incorporated into the protocol two years after enrollment.9

Results from OHTS supported previous observations about increased CCT in ocular hypertensives and further Slide 1

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identified decreased CCT as an independent risk factor and predictor of progression to primary open-angle glaucoma (POAG).10 After adjustment for other predictors, OHTS results demonstrated that a 40-micron thinner cornea presented approximately a 70% increase in the risk of developing glaucoma. Thinner CCT markedly increased the risk of progression to glaucoma within every range of IOP (Slide 1). A subsequent study of ocular hypertensive patients with early glaucomatous functional abnormalities, as detected using short wavelength automated perimetry (SWAP) or frequency doubling technology (FDT), had thinner CCT than ocular hypertensive patients with normal visual field results.11,12 Similarly, in patients with an established diagnosis of POAG, Herndon and colleagues13 found thinner CCT was significantly associated with more advanced disease at initial examination by a specialist.

The results of OHTS differed from the Early Manifest Glaucoma Trial (EMGT) conducted on patients with early glaucoma, which did not find any association between CCT and glaucoma progression.14 This discrepancy may be explained by the fact that OHTS enrolled patients based on high IOP that could have been falsely elevated due to increased CCT among this population, whereas the EMGT enrolled subjects with existing high pressure glaucoma and normal tension glaucoma. Thus, errors in IOP and CCT variability may have been reduced in this population. In fact, a study of patients diagnosed with preperimetric glaucomatous optic neuropathy found that patients with thinner corneas were more likely to progress to visual field loss15; patients with a 40-micron thinner cornea were at 60% increased risk of developing a visual field abnormality during follow up, a number similar to that found in OHTS.

A recent meta-analysis of the literature found that the mean corneal thickness of normal eyes was 544 microns.16 The mean thickness among ocular hypertensives in OHTS was 573. In addition to differences among normals, ocular hypertension, and patients with normal-tension glaucoma, other studies have identified race as a factor associated with CCT. Studies of CCT among different racial and ethnic groups have consistently demonstrated thinner corneas among patients of African origin compared with Caucasians,13,17-19 Hispanics, and Asians.19 In fact, adjusted IOP in African Americans was significantly higher than other races in young patients who underwent refractive surgery,19 again suggesting that thinner corneas may explain at least partially higher glaucoma risk in African Americans.

Conflicting findings exist regarding CCT and gender, age, and refractive error. Shimmyo and colleagues19 found that women had significantly thinner corneas than men, while OHTS found a slightly increased CCT in women.20 Other studies in Asian populations have demonstrated either no age: CCT relationship21 or an increased CCT in women of Eskimo origin.22 Most studies have found an inverse relationship between CCT and aging,17,21-23 while others have found none.7 It would appear that longer eyes should have thinner corneas, and while some studies have found an inverse relationship between refractive error and CCT,19,23 a large study of mixed-race subjects found no relationship between axial length and corneal thickness.24

CCT is an important variable in the diagnosis and classification of patients, as well as in setting target IOP given that many patients with “controlled” IOP are actually at higher pressure. Shih and colleagues36 point out that approximately 50% to 60% of eyes considered to have ocular hypertension may have normal IOP, and some 30% to 40% of eyes considered to have normal-tension glaucoma may have high IOP after correction of Goldmann applanation tonometry by CCT.” In a retrospective clinical study evaluating the effect of IOP adjustments based on CCT, they found that 20.2% of patients had an outcomes-significant IOP adjustment (defined as IOP adjustment of > 3 mm Hg).36

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CCT and the Etiology of Glaucoma Risk

Recall that OHTS found thinner CCT as an independent risk factor for the development of glaucoma among ocular hypertensives. While the predictive power of corneal thickness is at least partially due to its effect on the measured IOP, that does not explain the higher incidence of glaucoma among patients with thinner corneas. As such, the hypothesis that corneal thickness is intrinsically related to glaucomatous damage, independent of its effect on IOP measurement, cannot be excluded and needs further evaluation.

Postmortem studies have found anatomic differences in the lamina cribosa of glaucomatous eyes compared with normals33, and anatomical anomalies in the lamina have been postulated to play a role in the pathogenesis of glaucomatous damage.25, 34 Therefore, some have hypothesized that a possible correlation between thinner corneas and a thinner lamina cribosa may explain the susceptibility of eyes with decreased CCT to glaucoma. On the other hand, to date no such relationship has been found,26 and defining non-IOP dependent risk factors related to thinner corneas remains elusive.

A subsequent analysis of eyes in OHTS found that there was also a difference in the response to treatment between eyes with thinner versus thicker corneas. Individuals with thicker corneas actually had a smaller measured IOP response to ocular hypotensive medication than those with normal or thin corneas.27 The authors of the study proposed that their finding may be explained by a lower true baseline IOP in ocular hypertensives with thicker corneas. A second explanation was that corneal rigidity may have a greater effect on measured IOP at lower levels of IOP, which would tend to minimize the measured response to treatment in eyes with greater CCT.27

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IOP Measurement after Refractive Surgery

Myopia is a known glaucomatous risk factor, and any surgical change in CCT is likely to affect IOP determination by Goldmann applanation. IOP measurements after LASIK or photorefractive keratectomy (PRK) may be artificially decreased in eyes with glaucoma or ocular hypertension, and follow-up for such patients will continue to be confounded. Additionally, because glaucoma may develop decades after a Slide 2

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refractive procedure, it is important to document pre-LASIK/PRK IOP in order to closely follow patients at higher risk. Several studies have documented a significant reduction in IOP by applanation in eyes after PRK,28 and a mean decrease of 1.9 mm Hg to 3.8 mm Hg after LASIK.29,30 IOP measurements by pneumatonometry were shown to be slightly less influenced by post-LASIK corneal changes than applanation tonometry.30 However, IOP measurement may not be significantly affected in eyes undergoing mild to moderate surgical correction,31 suggesting that a critical amount of corneal change is needed to produce a significant change in IOP measurement.

An instrument that may help lessen the influence of CCT on IOP determination is the dynamic contour tonometer (DCT), which measures IOP based on contour matching. The concave DCT tip matches the radius of the central cornea and provides for a constant appositional force and contact area with a piezoresistive pressure sensor (Slide 2). Pressure readings are sampled, digitized, and computed by a microprosessor-based control unit. In cadaver eyes, the DCT measured IOP closer to actual values than either Goldmann applanation or pneumotonometry.32 In the absence of DCT, clinicians must recognize the degree of surgical reduction in CCT and its influence on IOP measurement and must follow post-refractive patients closely if glaucoma risk is suspected.

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Pachymetry

Given the relevance of CCT to clinical practice, accuracy in measuring this parameter is important. Ultrasound pachymetry (Paxis; Biovision Inc., Clermont-Ferrand, France) is currently a commonly used means of assessing CCT. Other devices are optical, and include the Orbscan system (Orbteck Inc., Salt Lake City, UT), which is commercially available and commonly used in preoperative refractive surgery evaluation, and partial coherence inferometry [(PCI) prototype system], which, similarly, is a noncontact optical system. Slide 3

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Comparison of these three methods demonstrated that CCT measured by ultrasound pachymetry was approximately 20 microns thicker than with the Orbscan or PCI.35 This discrepancy may be due to the optical systems’ lack of inclusion of the epithelium and endothelium. Rainer and colleagues35 concluded that the reproducibility and accuracy of all three methods are acceptable in measuring normal corneas.

When using the ultrasound pachymeter, the position of the probe must be perpendicular to the central cornea (Slide 3), as considerable variability in readings are obtained when not used carefully or by inexperienced hands. As such, repeated measurements on different clinical visits or by different operators should be obtained for more accurate assessment. Pachymetry should be performed at the beginning of each examination to avoid the effect of corneal desiccation on corneal thickness.

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Conclusion

Despite the known influence of corneal thickness on IOP measurements by applanation tonometry, CCT thickness measurement was largely ignored until the findings of OHTS demonstrated that thinner corneas are an independent risk factor for progression to glaucoma. Subsequent studies have shown the variability of CCT in different populations and the correlation of thinner corneas with glaucomatous visual field loss. These findings and the increasing frequency of refractive surgical procedures, which alter corneal thickness, make CCT determination an important variable in the clinical practice. Ultrasound pachymetry is reliable and, currently, the most commonly used clinical means of measuring CCT.

Although no universally accepted algorithm for CCT/IOP correction is available, it would be prudent to categorize patients on this basis as either having thin, average, or thick corneas; corneas below 540 microns would be considered thin and those above 555 microns considered thick. The patient’s standing along this spectrum would then be used not only to qualitatively assign a more realistic IOP, but also to acknowledge glaucomatous risk, which is the recommended approach until more reliable tools such as dynamic contour tonometry become readily available and the exact role of CCT in glaucoma risk is delineated.

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References

  1. Goldmann H, Schmidt T. Applanation tonometry [in German]. Ophthalmologica. 1957; 134:221-242.

  2. Ehlers N, Bramsen T, Sperling S. Applanation tonometry and central corneal thickness. Acta Ophthalmol (Copenh). 1975; 53:34-43.

  3. Whitacre MM, Stein RA, Hassanein K. The effect of corneal thickness on applanantion tonometry. Am J Ophtahlmol. 1993; 115:592-596.

  4. Mark HH. Corneal curvature in applanation tonometry. Am J Ophthalmol. 1973; 74:223-224.

  5. Argus WA. Ocular hypertension and central corneal thickness. Ophthalmol 1995; 102:1810-1812.

  6. Copt RP, Mermoud TR. Corneal thickness in ocular hypertension, primary open-angle glaucoma, and normal tension glaucoma. Arch Ophthalmol. 1999; 117:14-16.

  7. Wolfs RC, Klaver CC, Vingerling JR, et al. Distribution of central corneal thickness and its association with intraocular pressure: The Rotterdam Study. Am J Ophthalmol. 1997;123:767-772.

  8. 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.

  9. Gordon MO, Kass MA. The Ocular Hypertension Treatment Study: design and baseline description of the participants. Arch Ophthalmol. 1999; 117:573-583.

  10. 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.

  11. Medeiros FA, Sample PA, Weinreb RN. Corneal thickness measurements and frequency doubling technology perimetry abnormalities in ocular hypertensive eyes. Ophthalmology. 2003; 110:1903-1908.

  12. Medeiros FA, Sample PA, Weinreb RN. Corneal thickness measurements and visual function abnormalities in ocular hypertensive patients. Am J Ophthalmol. 2003;135:131-137.

  13. Herndon LW, Weizer JS, Stinnett SS. Central corneal thickness as a risk factor for advanced glaucoma damage. Arch Ophthalmol. 2004;122:17-21.

  14. Leske MC, Heijil A, Hussein M, et al. Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial. Arch Ophthalmol. 2003; 121:48-56.

  15. Medeiros FE, Sample PA, Zangwill LM. Corneal thickness as a risk factor for visual field loss in patients with preperimetric glaucomatous optic neuropathy. Am J Ophthalmol. 2003; 136:805-813.

  16. Dougherty MJ, Zaman ML. Human corneal thickness and its impact on intraocular pressure measurements: a review and meta-analysis. Surv Ophthalmol. 2000; 44:367-408.

  17. Nemesure B, Wu Suh-Yuh, Hennis A, Leske MC. Corneal thickness and intraocular pressure in the Barbados eye study group. Arch Ophthalmol. 2003; 121:240-244.

  18. La Rosa FA, Gross RL, Orengo-Nania S. Central corneal thickness of Caucasians and African-Americans in glaucomatous and non-glaucomatous populations. Arch Ophthalmol. 2001; 119:23-27.

  19. Shimmyo M, Ross AJ, Moy A, Mostafavi R. Intraocular Pressure, Goldmann applanation tension, corneal thickness, and corneal curvature in Caucasians, Asians, Hispanics, and African Americans. Am J Ophthalmol. 2003; 136:603-613.

  20. Brandt JD, Beiser JA, Kass MA, Gordon MO. Central corneal thickness in the ocular hypertension treatment study (OHTS). Ophthalmology. 2001; 108:1779-1788.

  21. Foster PJ, Bassanhu J, Alsbirk PH, et al. Central corenal thickness and intraocular pressure in a Mongolian population. Ophthalmology. 1998; 105:969-973.

  22. Alsbirk PH. Corneal thickness: age variation, sex difference and oculometric correlation. Acta Ophthalmol. 1978; 56:95-104.

  23. Li JH, Zhou F, Zhou SA. Research on corneal thickness at multi-points in normal and myopic eyes [in Chinese]. Chinese J Ophthalmol. 1994; 30:445-448.

  24. Shimmyo M, Orloff PN. Corneal thickness and axial length. Am J Ophthalmol. 2004; 139:553-554.

  25. Spoerl E, Goehm A, Pillunat L. The influence of various substances on the biomechanical behavior of lamina cribrosa and peripapillary sclera. Invest Ophthalmol Vis Sci. 2005; 46:1286-1290.

  26. Jonas JB, Holbach L. Central corneal thickness and thickness of the lamina cribrosa in human eyes. Invest Ophthalmol Vis Sci. 2005; 46:1275-1279.

  27. Brandt JD, Beiser JA, Gordon MO, Kass MA. Central corneal thickness and measured IOP response to topical ocular hypotensive medication in the Ocular Hypertension Treatment Study. Am J Ophthalmol. 2004; 138:717-722.

  28. Merdelli PG, Piebenga LW, Whitacre MM, Siegmund KD. The effect of eximer laser photorefractive keratomy on intraocular pressure measurements using Godmann applanation tonometer. Surv Ophthalmol. 1997; 104:945-949.

  29. Fournier AV, Podtetenev M, Lemire J, et al. intraocular pressure change measured by Goldmann tonometry reading after corneal refractive surgery. J Cataract Refract Surg. 1998; 23:905-910.

  30. Zadok D, Tran DB, Twa M, et al. Pneumatonometry versus Goldmann tonometry after laser in situ keratomileusis for myopia. J Cataract Refract Surg. 1999; 25:1344-1348.

  31. Vakili R, Choudhri SA, Tauber S, Shields MB. Effect of mild to moderate myopic correction by laser-assisted in situ keratomileusis on intraocular pressure measurements with Goldmann applanation tonometer, Tono-Pen, and pneumatonometer. J Glaucoma. 2002; 11:493-496.

  32. Kniestedt C, Nee M, Stamper RL. Dynamic contour tonometry: a comparative study on human cadaver eyes. Arch Ophthalmol. 2004;122:1287-1293.

  33. Quigley EN, Quigley HA, Pease ME, Kerrigan LA. Quantitative studies of elastin in the optic nerve heads of persons with primary open-angle glaucoma. Ophthalmology. 1996;103(10):1680-5.

  34. Quigley HA, Hohman RM, Addicks EM, Massof RW, Green WR. Morphologic changes in the lamina cribrosa correlated with neural loss in open-angle glaucoma. Am J Ophthalmol. 1983:673-691.

  35. Rainer G, Findl O, Petternel V, Kiss B, Drexler W, Skorpik C, Georgopoulos M, Schmetterer L. Central corneal thickness with partial coherence Interferometry, ultrasound, and the Orbscan system. Ophthalmology. 2004;111:875-879.

  36. Shih CY, Graff Zivin JS, Trokel SL, Tsai JC. Clinical significance of central corneal thickness in the management of glaucoma. Arch Ophthalmol. 2004; 122:1270-1275.

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