Human corneal thickness and its impact on intraocular pressure measures: a review and meta-analysis approach.

We determined the "normal" central corneal thickness (CCT) value in human corneas based on reported literature values for within-study average CCT values, and used this as a reference to assess the reported impact of physiological variables (especially age and diurnal effects), contact lens wear, pharmaceuticals, ocular disease, and ophthalmic surgery on CCT. With the expected CCT and its variance defined, it should be possible to determine the potential impact of differences in CCT in intraocular pressure (IOP) assessments, especially by applanation tonometry, using a meta-analysis approach. Some 600 sets of CCT data were identified from the worldwide literature over the period of 1968 through mid-1999, of which 134 included IOP measures as well. The within-study average CCT values and reported variance (SD) was noted along with the number of eyes and any special characteristics, including probable ethnic origin of the study subjects. Various sets of data were subjected to statistical analyses. From 300 data sets from eyes designated as normal, the group-averaged CCT was 0.534 mm. From 230 data sets where interindividual variance was reported, the group-averaged CCT was 0.536 mm (median 0.536 mm; average SD of 0. 031 mm, average coefficient of variation = 5.8%). Overall, studies using slit-lamp-based pachometry have reported marginally lower CCT values (average 0.530 mm, average SD 0.029 mm) compared to ultrasound-based studies (average 0.544, average SD 0.034 mm), which perhaps reflects the type of individual studied (non-surgical vs. pre-surgical patients) rather than the technique itself. A slight chronological increase in reported average CCT values (approximately 0.006 mm/decade) was evident, but a substantial chronological increase was evident for ultrasound pachometry studies (approximately 0.015 mm/decade). Within the meta-analysis-generated average and variance, age had no obvious impact on CCT measures for *whites, although an age-related decline in CCT is evident for non-whites. Any diurnal effects are likely concealed within the expected variance in CCT. Contact lens wear and pharmaceuticals generally produced changes in CCT that were well within the expected variance in CCT. Of the ocular diseases, only those associated with collagen disorders (including keratoconus) or endothelial-based corneal dystrophies (e.g., Fuchs) were likely to result in decreases or increases, respectively, of CCT beyond the normal variance. Routine contact lens wear and diseases such as diabetes seem unlikely to produce changes in CCT of a magnitude that would justify pachometry as a monitoring method beyond routine slit-lamp evaluation. Increases in CCT beyond the expected variance were reported after a range of intraocular surgeries (cataract operations, penetrating keratoplasty), whereas photorefractive surgery produces a measurable decrease in CCT. A meta-analysis of possible association between CCT and IOP measures of 133 data sets, regardless of the type of eyes assessed, revealed a statistically significant correlation; a 10% difference in CCT would result in a 3. 4 +/- 0.9 mm Hg difference in IOP (P </= 0.001, r = 0.419). The observed phenomenon was much smaller for eyes designated as healthy (1.1 +/- 0.6 mm Hg for a 10% difference in CCT, P = 0.023, r = 0. 331). For eyes with chronic diseases, the change was 2.5 +/- 1.1 mm Hg for a 10% difference in CCT (P = 0.005, r = 0.450), whereas a substantial but highly variable association was seen for eyes with acute onset disease (approximately 10.0 +/- 3.1 mm Hg for a 10% difference in CCT, P = 0.004, r = 0.623). Based on the meta-analysis, normal CCT in white adults would be expected to be within +/-11.6% (+/-2 SD) of 0.535 mm, i.e., 0.473-0.597 mm (95% CI, 0.474-0.596). The impact of CCT on applanation tonometry of healthy eyes is unlikely to achieve clinical significance, but for corneas of eyes with chronic disease, pachometry should be performed if the tonometry reveals IOP readi