Is corneal thickness an independent risk factor for glaucoma?

c p t n i e a d m C i d The Ocular Hypertension Treatment Study (OHTS) showed that central corneal thickness (CCT) was a significant predictor of which patients with ocular hypertension are at higher risk for converting to glaucoma. Eyes with CCT of 555 m or less had a 3-fold greater risk of developing glaucoma compared with eyes that had CCT of more than 588 m. In a multivariable model including age, baseline intraocular pressure (IOP) (measured by Goldmann tonometer, Haag Streit, Koeniz, Switzerland), optic disc topography (cup:disc ratio), and visual field (pattern standard deviation), CCT retained its statistical significance as a predictor of glaucoma development, with a hazard ratio of 1.82 for each 40 m thinner CCT. The results of this report have been mistakenly interpreted by some investigators as demonstrating that CCT is an independent risk factor for the development of glaucoma. As Goldmann applanation tonometry (GAT) measurements ultimately depend on CCT, it is impossible in the original model to completely disentangle the effects of both. For example, consider 2 patients with the same baseline GAT IOP of 24 mmHg, but with corneal thicknesses of 520 and 560 m. The adjusted hazard ratio for CCT in the OHTS multivariable model would indicate that the risk for developing glaucoma for the one with the thin cornea would be 82% higher. However, it is impossible to determine from the original analysis whether the increased risk is caused by a true independent effect of corneal thickness per se, or simply due to the effect of CCT on GAT measurement error. In fact, using a correction formula proposed by Ehlers et al, the patient with the thinner cornea would have “corrected” IOP close to the measured value of 24 mmHg. In contrast, the “corrected” IOP would be 2.8 mmHg lower at approximately 21 mmHg for the patient with the thicker cornea. So, the increased risk could ultimately be caused by the fact that the first patient actually has a higher “true” IOP. However, some authors have suggested that the predictive effect of CCT is not fully accounted for by its induced GAT measurement error, but rather that there is a possible association between corneal thickness and structural measures possibly related to glaucoma risk, such as scleral or lamina cribrosa thickness. Whether corneal thickness is a true independent risk factor for glaucoma has remained an unanswered question. In this issue of Ophthalmology, Brandt et al attempt to shed light on this issue. They evaluated whether the OHTS prediction model could be improved by correcting IOP for CCT using previously published formulas. The rationale of the authors was that if the influence of CCT on GAT fully explains the role of CCT as a predictive factor, than inclusion of CCT-corrected IOP values in the model would cause CCT to become nonsignificant. They show that models with CCT-corrected IOP do not perform better than the original i