Corneal Thickness and Glaucoma Medications

Abstract

We write concerning the comprehensive article by Stewart et al1Stewart W.C. Konstas A.G. Nelson L.A. Kruft B. Meta-analysis of 24-hour intraocular pressure studies evaluating the efficacy of glaucoma medicines.Ophthalmology. 2008; 115: 1117-1122Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar entitled “Meta-analysis of 24-hour intraocular pressure studies evaluating the efficacy of glaucoma medicines,” which was published in July 2008 issue. In that article, it was stated that mean diurnal intraocular pressure (IOP) decrease was significantly greater with prostaglandin analogues (bimatoprost [29%], travoprost [27%], and latanoprost [24%]) compared with timolol (19%) and dorzolamide (19%). These results imply that prostaglandin analogues have better efficacy in the treatment of glaucoma. Based on the alterations in central corneal thickness (CCT) after topical anti-glaucoma therapy as a confounding factor, we offer an explanation for the greater decrease in apparent IOP measurements in these agents. Recently, several studies have been conducted to evaluate the effect of different anti-glaucoma medications on CCT. Accordingly, it was shown that topical application of prostaglandin PGF2alpha analogues onto the cornea reduces the CCT.2Stefan C. Dumitrica D.M. Tebeanu E. et al.Prostaglandin analogues and central corneal thickness.Oftalmologia. 2007; 51: 95-99PubMed Google Scholar, 3Viestenz A. Martus P. Schlötzer-Schrehardt U. et al.Impact of prostaglandin-F(2alpha)-analogues and carbonic anhydrase inhibitors on central corneal thickness – a cross-sectional study on 403 eyes.Klin Monatsbl Augenheilkd. 2004; 221: 753-756PubMed Google Scholar The authors attributed these changes to PGF2alpha induced upregulation of matrix metalloproteinases and subsequent effects on the extracellular matrix of the corneal stroma.3Viestenz A. Martus P. Schlötzer-Schrehardt U. et al.Impact of prostaglandin-F(2alpha)-analogues and carbonic anhydrase inhibitors on central corneal thickness – a cross-sectional study on 403 eyes.Klin Monatsbl Augenheilkd. 2004; 221: 753-756PubMed Google Scholar In addition, there is evidence that topical use of timolol and carbonic anhydrase inhibitors (CAI) lead to significant increase in CCT.3Viestenz A. Martus P. Schlötzer-Schrehardt U. et al.Impact of prostaglandin-F(2alpha)-analogues and carbonic anhydrase inhibitors on central corneal thickness – a cross-sectional study on 403 eyes.Klin Monatsbl Augenheilkd. 2004; 221: 753-756PubMed Google Scholar, 4Grüb M. Leitritz M. Mielke J. et al.Effect of timolol on central corneal thickness and endothelial cell density.Klin Monatsbl Augenheilkd. 2006; 223: 894-898Crossref PubMed Scopus (15) Google Scholar In a recent large randomized controlled trial, Brandt et al5Brandt J.D. Gordon M.O. Beiser J.A. et al.Ocular Hypertension Treatment Study GroupChanges in central corneal thickness over time: the ocular hypertension treatment study.Ophthalmology. 2008; 115 (1556.e1): 1550-1556Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar verified that even in a multivariate analysis prostaglandin analogues were associated with more corneal thinning over time compared with β-blockers. As we know, increased CCT leads to an artificially high, and decreased CCT an artificially low, lOP measurement.6Liesegang T.J. Skuta G.L. Cantor L.B. Basic and Clinical Science Course, Glaucoma. American Academy of Ophthalmology, San Francisco, CA2007–2008Google Scholar The Goldmann tonometer, Perkins tonometer, pneuma tonometer, noncontact tonometer, and Tonopen are all influenced by CCT. Therefore, CCT changes after topical anti-glaucoma treatment may result in under or overestimation of IOP levels. Although some investigators proposed that the modest drug-related changes in corneal thickness are unlikely to influence tonometry,5Brandt J.D. Gordon M.O. Beiser J.A. et al.Ocular Hypertension Treatment Study GroupChanges in central corneal thickness over time: the ocular hypertension treatment study.Ophthalmology. 2008; 115 (1556.e1): 1550-1556Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar they did not investigate this issue specifically. Since the alterations in the extracellular matrix of the corneal stroma observed with prostaglandin analogues may also affect the corneal resistance factor and hysteresis, these drugs may significantly confound the routine IOP measurements despite modest change in CCT. In conclusion, on the basis of the IOP reduction alone, we cannot deduce that prostaglandin analogues have better efficacy than timolol and CAIs. Future trials using the dynamic contour tonometer (Pascal tonometer) or the Ocular Response Analyzer, which measure IOP independent of corneal properties and/or CCT,7Hager A. Loge K. Schroeder B. et al.Effect of central corneal thickness and corneal hysteresis on tonometry as measured by dynamic contour tonometry, ocular response analyzer, and Goldmannn tonometry in glaucomatous eyes.J Glaucoma. 2008; 17: 361-365Crossref PubMed Scopus (53) Google Scholar may minimize the confounding effect of corneal conditions induced by anti-glaucoma medications. Alternatively, the controlled studies which provide outcome data based on visual field and/or nerve fiber layer thickness analysis rather than IOP may offer more reliable results. Author replyOphthalmologyVol. 116Issue 7PreviewI would like to thank doctors Mehdizadeh, Tehrani, and Nowroozzadeh for their time and effort to respond to our recent article.1 I agree with the authors in that an analysis of the intraocular pressure (IOP) results based on central corneal thickness (CCT) would have been instructive. However, that was not a goal of our paper, and CCT results were not available from all of the included studies because some of these were published before this procedure was routinely performed. Full-Text PDF