10.2.2  CCT Over Time

Central corneal thickness appears to hold reasonably steady over time in an individual. Among the largest population and clinical trial-based studies, cross-sectional estimates of time-dependent changes in CCT suggest that on average, CCT either remains unchanged or decreases by up to 0.6 µm/year [13, 14, 17–21]. The only large longitudinal study of time-dependent changes in CCT was performed by the OHTS, which found a rate of corneal thinning of −0.74 ± 3.5 µm/year among its ocular hypertensive participants [22].

OHTS/EGPS risk model features CCT as a major component of glaucoma risk [26].

The OHTS and EGPS results suggest that many ocular hypertensive and “glaucoma suspect” patients are being misclassified in terms of glaucoma risk on the basis of erroneous IOP estimates by GAT. Clearly many individuals with elevated GAT measurements but no other findings suggestive of glaucoma probably have normal “true” IOPs and do not need treatment or even increased glaucoma surveillance.

Summary for the Clinician

››African Americans tend to have thinner corneas than Hispanics who tend to have thinner corneas than Whites.

››CCT has been reported as the most highly heritable aspect of ocular structure.

››CCT holds steady over time in an individual.

10.3  Does CCT Predict Glaucoma?

10.3.1  Clinical Trials

The importance of CCT in the management of glaucoma patients, particularly those with ocular hypertension, was brought to the forefront by findings from the Ocular Hypertension Treatment Study (OHTS) [23]. Among the OHTS participants, African American participants had thinner corneas than their Caucasian counterparts, and 25% of the overall OHTS cohort had CCT values above 600 µm [13]. If one uses Ehler’s correction of roughly 7 mmHg/100 µm deviation from the nominal value of 520 µm, then as many as 50% of OHTS subjects had “corrected” IOP values upon entry £21 mmHg! Most dramatically, in the OHTS multivariate model of baseline characteristics predictive of conversion to glaucoma, CCT proved to have the largest impact on glaucoma risk [23]. These findings have been confirmed independently in the European Glaucoma Prevention Study (EGPS) [24, 25], and the merged

10.3.2  CCT in Established Glaucoma

CCT measurements in patients with diagnosed glaucoma also appear useful; following the OHTS publications, numerous investigators have explored the role of CCT in patients with existing glaucoma, and they have generally found CCT to have a significant impact in these patients as well [27–34]. However the role of CCT in established glaucoma has not been confirmed as convincingly as for ocular hypertension in prospective, randomized clinical trials. The Early Manifest Glaucoma Trial (EMGT) initially found no relationship between CCT and either incident glaucoma or glaucomatous progression; with longer follow-up however, the EMGT researchers report a modest relationship between CCT and glaucoma progression, but only for individuals with elevated IOPs [35].

10.3.3  CCT as a Biological Risk Factor

The relationship between CCT and either glaucoma risk or glaucoma progression cannot be explained solely by tonometry artifact. Attempts by the OHTS investigators to adjust IOP data for CCT have failed to eliminate CCT from the risk models. This would suggest that either the published correction algorithms are incorrect, that more than CCT is involved in the tonometry artifact (and thus can’t be adjusted away), or perhaps that CCT is linked biologically to glaucoma risk. One intriguing hypothesis is that CCT is linked somehow to the engineering of the optic nerve head. Studies examining the movement of the lamina cribrosa in patients after IOP-lowering intervention have been equivocal [36, 37]. However, the