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Intraocular Pressure Measurements and Biomechanical Properties of the Cornea in Eyes After Penetrating Keratoplasty
Intraocular Pressure Measurements and Biomechanical Properties of the Cornea in Eyes After Penetrating Keratoplasty IDO D. FABIAN, IRINA S. BAREQUET, ALON SKAAT, EHUD RECHTMAN, MORDECHAI GOLDENFELD, CYNTHIA J. ROBERTS, AND SHLOMO MELAMED ● PURPOSE: To compare intraocular pressure (IOP) mea-
surements obtained using the Goldmann applanation tonometer (GAT; Haag-Streit), the Tono-Pen XL (Reichert, Inc), and the ocular response analyzer (ORA; Reichert Ophthalmic Instruments), and to determine the influence of corneal factors on IOP measurements in eyes that had undergone penetrating keratoplasty (PK). ● DESIGN: Consecutive, prospective study. ● METHODS: Study population. Sixty-one eyes that underwent PK were enrolled in this study. Intervention. IOP was measured using the GAT, Tono-Pen, and ORA. Corneal hysteresis and corneal resistance factor as provided by the ORA were recorded. Central corneal thickness was measured using an ultrasound pachymeter. Main outcome measures. IOP and corneal biomechanical factors. ● RESULTS: IOP measurements were obtained in an average of 65 months (range, 6 to 209 months) after PK surgery. ORA-derived IOP measurements (corneal-compensated IOP and Goldmann-correlated IOP) and TonoPen XL IOP all correlated in a significant manner to GAT IOP measurements. Corneal-compensated IOP and Tono-Pen XL IOP values were higher than GAT IOP (P < .001 and P ⴝ .001, respectively), whereas Goldmann-correlated IOP readings did not differ from GAT IOP readings (P ⴝ .054). Central corneal thickness did not correlate to any tonometry technique. In a regression analysis, corneal hysteresis and corneal resistance factor were found to play a role in IOP prediction. ● CONCLUSIONS: Central corneal thickness may be of less importance than corneal hysteresis and corneal resistance factor in IOP determination in eyes that have undergone PK, perhaps because of the lower modulus of elasticity in these eyes. GAT IOP seems to be lower than other tonometry techniques in eyes that have undergone PK. (Am J Ophthalmol 2011;151:774 –781. © 2011 by Elsevier Inc. All rights reserved.) Accepted for publication Nov 9, 2010. From the Goldschleger Eye Institute, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (I.D.F., I.S.B., A.S., E.R., M.G., S.M.); and the Department of Ophthalmology and Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio, USA (C.J.R.). Inquiries to Ido D. Fabian, Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer 52621, Israel; e-mail: [email protected]
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elevated intraocular pressure (IOP) in eyes that have undergone penetrating keratoplasty (PK) is very important, because increased IOP in these patients may cause progressive endothelial cell loss and eventually may lead to transplant failure.1 In addition, glaucoma is considered to be one of the most common causes for irreversible visual loss in eyes that have undergone PK.2 However, diagnosis of glaucoma after PK is a major clinical problem because of inconsistency in IOP measurements caused by graft irregularities,3 thick or astigmatic corneal graft, and irregular corneal surface epithelium.4 Patients who have undergone PK are prone to glaucoma development because of distortion of the angle, collapse of the trabecular meshwork, or peripheral anterior synechiae formation, which was found to be the main cause for late-onset post-PK glaucoma.5,6 Further causes may be steroid-induced glaucoma, development of postoperative inflammation, or pre-existing glaucoma. Occurrence of glaucoma in patients who have undergone PK was shown to be higher compared with that in the general population, with a rate of up to 14% in the immediate postoperative phase and up to nearly 30% in the long term.2,7–10 An early and accurate detection of increased IOP in eyes that have undergone PK therefore is crucial not only to preserve the optic nerve and to prevent functional visual field loss, but also to maintain the survival of the corneal graft. Several tonometers are available for the measurement of IOP in clinical practice. The Goldmann applanation tonometer (GAT; Haag-Streit, Bern, Switzerland), which is considered the gold standard tonometer in clinical practice for normal corneas, may be less accurate in eyes that have undergone PK, because it was shown to be influenced by various parameters, such as central corneal thickness (CCT), corneal curvature, and cornea structure.11–16 The Tono-Pen XL (Reichert, Inc, Depew, New York, USA) is a hand-held instrument based on the MacKayMarg principle that uses a microstrain gage technology and a small transducer tip used for applanation of the cornea. The Tono-Pen XL was shown to be less affected by CCT and ocular surface abnormalities compared with GAT, as
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0002-9394/$36.00 doi:10.1016/j.ajo.2010.11.007
TABLE 1. Intraocular Pressure and Corneal Biomechanical Readings in Eyes after Penetrating Keratoplasty
Ocular response analyzer IOPcc IOPg Goldmann applanation tonometer Tono-Pen XL Central corneal thickness Corneal hysteresis Corneal resistance factor
No. Eyes
Mean (mm Hg)
SD (mm Hg)
Range (mm Hg)
51 51 51 49 50 51 51
16.8 15.1 14.2 15.9 585.9a 9.5 9.5
4.1 4.2 4.4 3.5 86.2a 2.8 3.0
7.9 to 27.8 8.1 to 27.1 5.5 to 26.5 8.3 to 24.3 470.0 to 796.0a 4.6 to 17.7 4.8 to 18.3
IOPcc ⫽ corneal-compensated intraocular pressure; IOPg ⫽ Goldmann-correlated intraocular pressure; SD ⫽ standard deviation. a Micrometers.
demonstrated in eyes that underwent PK and that underwent epikeratophakia.17 The Reichert ocular response analyzer (ORA; Reichert Ophthalmic Instruments, Buffalo, New York, USA) is a novel noncontact tonometer that uses a rapid air pulse and an electro-optical system to record 2 applanation pressure measurements: one while the cornea moves inward (P1) and the other in the outward direction (P2), while the cornea returns to its normal state. The average of the 2 measurements provides the Goldmann-correlated IOP (IOPg) value. Corneal-compensated IOP (IOPcc) is a linear combination of P1 and P2 that is empirically derived to be less sensitive to errors related to corneal properties, when compared with other tonometry techniques18,19 (Luce D. IOVS 2006;47:E-abstract 2266). A new viscoelastic parameter known as corneal hysteresis (CH) was defined, which is the difference of the 2 applanation pressure measurements. The ORA also provides an additional viscoelastic parameter that was designed empirically to have maximal correlation with central corneal thickness, which is the corneal resistance factor (CRF; Luce D. IOVS 2006;47:E-abstract 2266). The aim of this study was to compare IOP measurements obtained by the GAT, the Tono-Pen XL, and the ORA in eyes that had undergone PK and to investigate the influence of biomechanical parameters, including CH, CRF, and CCT, on IOP measurement using these 3 common tonometer technologies.
METHODS THE STUDY WAS PERFORMED IN A PROSPECTIVE MANNER
from May 2009 through October 2009. Patients eligible for the study were subjects who underwent PK for various corneal pathologic characteristics at least 6 months before the current study and were followed-up at the Cornea Clinic at Goldschleger Eye Institute. Subjects were excluded from the analysis if measurements, using the ORA VOL. 151, NO. 5
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were not obtainable because of poor fixation, rejected grafts, or significant corneal edema. Subjects were given an empty envelope, with which they moved from one examination station to another through a predesigned course. Each parameter was recorded on a designed sheet, which was given to the subject and sealed in the envelope. After going through all examination stations, the envelope was delivered to one of the authors (I.D.F.), who copied all data to a case report form. Each of the 3 IOP-measuring technologies was implemented by a single different observer (one of the authors) who was masked to previous IOP measurements to reduce interoperator bias. To minimize the potential confounding effect of diurnal variation in IOP, all measurements were obtained in the morning between 9 and 11 am, with a 10-minute interval between readings. All tonometers were calibrated according to manufacturer’s guidelines. Measurements with the ORA were obtained first, before instillation of topical corneal anesthesia to avoid decrease in IOPcc, as previously reported.20 Up to 4 measurements were obtained, and the result with the highest waveform score was used for analysis to obtain IOPcc, IOPg, CH, and CRF parameters. After ORA examination, a corneal topography scan (Keratron Corneal Analyzer; Optikon 2000, Rome, Italy) was performed followed by ultrasonic pachymetry measurements (Altair Ultrasonic Pachymeter; Optikon 2000). The mean of 3 readings was recorded as the CCT value. IOP measurements using the GAT and Tono-Pen XL subsequently were obtained in a randomized fashion. Using the GAT, an average between the horizontal and the vertical measurement was used to overcome highly astigmatic corneas, as described previously.21 A total of 3 consecutive measurements were obtained and averaged. For Tono-Pen XL measurements, a disposable cap was used for each subject and an average of 3 measurements was used for analysis. We accepted only values with a coeffiAFTER
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TABLE 2. Intraocular Pressure and Corneal Structural Factors of Eyes after Penetrating Keratoplasty with and without Corneal Sutures 95% Confidence Interval of the Difference
Intraocular pressure measurements Ocular response analyzer IOPcc IOPg Goldmann applanation tonometer Tono-Pen XL Corneal biomechanical factors Central corneal thickness Corneal hysteresis Corneal resistance factor
Presence of Corneal Sutures
Mean Value (mm Hg)
Significance (2-tailed)a
Upper
Lower
⫹ – ⫹ – ⫹
16.34 17.19 14.88 15.32 13.93
0.463
–3.17
1.46
0.711
–2.81
1.93
0.631
–3.10
1.90
– ⫹ –
14.53 15.41 16.34
0.360
–2.93
1.08
⫹ – ⫹ – ⫹ –
579.41b 593.57b 9.87 9.16 9.82 9.19
0.568
–63.66b
35.35b
0.380
–0.90
2.33
0.471
–1.11
2.36
⫹ ⫽ corneal sutures are present; – ⫽ corneal sutures are not present; IOPcc ⫽ corneal-compensated intraocular pressure; IOPg ⫽ Goldmann-correlated intraocular pressure. a Micrometers. b t Test, equal variances assumed.
surements and IOP measured by all other tonometers. A P value less than .05/3 ⫽ 0.0167 was considered significant.
cient of variation (standard deviation divided by the mean) of 5% or less. In addition, all subjects underwent a routine ophthalmologic examination, including best-corrected visual acuity, slit-lamp examination of the anterior segment, and fundus examination. Axial length measurements were performed with an ultrasonic biometer (model 820; Allergan, Humphrey, San Leandro, California, USA). Data regarding demographics, corneal basic pathologic features, surgical details, and current medical treatment were retrieved from the medical records and analyzed.
RESULTS A TOTAL OF 61 EYES OF 51 PATIENTS WHO UNDERWENT PK
were enrolled in our study. Of these, 10 eyes (16.39%) of 9 patients with best-corrected visual acuity of hand movements or worse were excluded because they could not fixate on the signaling light inside the ORA instrument. The cohort comprised 22 males and 20 females, with a mean age of 54 ⫾ 19 years (range, 18 to 91 years). The original diseases were keratoconus (n ⫽ 23), stromal dystrophies (n ⫽ 4), stromal opacity occurring after herpes keratitis (n ⫽ 9), stromal opacity occurring after bacterial or fungal corneal abscesses (n ⫽ 6), penetrating injuries (n ⫽ 4), and pseudophakic bullous keratopathy (n ⫽ 5). Measurements for our study were obtained in a mean time of 65 ⫾ 41 months after PK surgery (range, 6 to 209 months). Fourteen eyes (27.45%) had also a diagnosis of glaucoma before the enrollment in the study and were treated with topical antiglaucoma medication. Using the Tono-Pen XL for 2 subjects, measurements could not
● STATISTICAL ANALYSIS: All calculations were performed and presented using Microsoft Excel 2003 (Microsoft Corporation, Redmond, Washington, USA) and SPSS software version 15.0 (SPSS, Inc, Chicago, Illinois, USA). The Pearson correlation was used to assess the dependence of the different tonometry techniques on corneal biomechanical parameters (ie, CCT, CH, and CRF). Multivariate analyses were undertaken to predict IOP measurements, taking into account the aforementioned parameters (ie, demographic, operative, and postoperative data). The level of significance was chosen at P ⬍ .05. The Paired t test with Bonferroni correction for multiple comparisons was used to assess the differences between GAT IOP mea776
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FIGURE 1. Graphs showing correlations between intraocular pressure (IOP) measured by (Top left) the Goldmann applanation tonometer (GAT; Haag-Streit, Bern, Switzerland) and corneal-compensated IOP (IOPcc), R2 ⴝ 0.4351 (P < .001); (Top right) Goldmann-correlated IOP (IOPg), R2 ⴝ 0.5239 (P < .001); and (Bottom) the Tono-Pen XL (Reichert, Inc Depew, New York, USA), R2 ⴝ 0.363 (P < .001).
be obtained. Table 1 lists the IOPs as measured by each of the 3 tonometers. Twenty-eight (54.90%) eyes had graft sutures still present at the time of measurements. No significant statistical difference was found in IOP measurements of eyes with or without corneal sutures using the various tonometry techniques, as shown in Table 2. In the same manner, no significant difference was found in the values of the structural corneal factors (ie, CCT, CH, and CRF) when subdividing into eyes with corneal sutures and without (Table 2). The mean keratometry readings were 47.92 diopters (D; range, 37.42 to 59.50 D) and 41.92 D (range, 30.22 to 49.02 D) for the steep and flat meridians, respectively. The mean corneal astigmatism was 5.88 D (range, 0.00 to 18.02 D). No correlation was found between IOP, corneal biomechanical factors, or time gap between corneal transplant surgery and measurements and corneal curvature measurements (P ⱖ .08). All IOP measurements were found to correlate in a significant manner with GAT IOP measurements, with IOPg measured by the ORA displaying the highest correlation (R2 ⫽ 0.5239, P ⬍ .001; Figure 1). The distribution of IOP is shown in box-and-whisker plots for each tonomVOL. 151, NO. 5
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etry technique used (Figure 2). IOPcc measurements were the highest, followed by the Tono-Pen XL. Both were significantly different from GAT measurements, whereas IOPg did not differ from GAT, as shown in Table 3. The Tono-Pen XL was the only tonometer that inversely correlated, in a significant manner, to the time gap between PK surgery and measurements performed during our study (Pearson correlation, ⫺0.395; P ⫽ .006). IOP measurements using all other tonometers did not correlate significantly to the time from PK surgery and the present study. CCT, CH, and CRF results are shown in Table 1. Mean CCT was 585.92 ⫾ 86.18 m (range, 470.00 to 769.00 m). CCT did not correlate significantly to any of the tonometers (Figure 3). Furthermore, CCT did not correlate to any of the tonometry techniques even after subdividing the cohort to 2 subgroups, above and beneath the median CCT measure (550 m). Table 4 shows the relationship between the corneal biomechanical characteristics, that is, CCT, CH, and CRF, and the different tonometry techniques. CH was inversely related to IOPcc, whereas all other tonometry techniques were not influenced by CH. CRF correlated in a significant manner to IOPg and Tono-Pen XL only (Table 4). AFTER
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TABLE 3. Differences between Average Intraocular Pressure Values Measured by the Ocular Response Analyzer (IOPcc and IOPg) and the Tono-Pen XL and Intraocular Pressure Measured by the Goldmann Applanation Tonometer
2.52 0.88 1.76
P ⬍ .001 P ⫽ .054 P ⫽ .001
when analysis of the entire cohort study was performed nor when compared with a subgroup of eyes with CCT of 550 m or less. Medeiros and Weinreb compared GAT and ORA tonometry in normal eyes and found that the tonometers differed in a significant manner in relation to CCT: patients with thicker corneas tended to have higher GAT IOP measurements compared with IOPcc, whereas in patients with thin corneas, GAT IOP measurements tended to be lower than IOPcc.18 However, comparison of findings based on measurements in normal eyes with the eyes in the current study probably is irrelevant, because CCT was shown not to correlate to any of the tonometry techniques in eyes that underwent PK. It is interesting that although none of our cases displayed corneal edema at the time of measurement, GAT IOP still gave the lowest value. We can speculate that parameters other than CCT and corneal edema contribute to this measurement in PK eyes. It has been shown in a theoretical analysis that corneal biomechanical properties, specifically modulus of elasticity, has a greater effect on GAT measurement error than CCT.16 In fact, it was shown further that the elastic modulus determines the relationship of GAT measurement error to CCT, with stiffer corneas of higher modulus having a stronger relationship to CCT than softer corneas with a lower modulus. Because CCT was shown to have no correlation to tonometry in the current study and GAT measurements were lower than those of other techniques, this may suggest that corneas that have undergone PK have lower elastic modulus than normal corneas. This may not be reflected in the CH or CRF parameters, which are viscoelastic in nature and respond to changes in both elasticity and viscosity. No difference was found in IOP, CCT, CH, or CRF values between corneas with and without sutures (Table 2); therefore, no correction factor is needed when measuring these parameters in eyes that have undergone PK with regard to the presence or absence of corneal sutures.
DISCUSSION MEASURING IOP IN AN ACCURATE MANNER IS OF GREAT
importance, especially in eyes that are prone to elevated IOP developing, such as eyes that have undergone PK.2,7–10 Delay in detection and treatment of elevated IOP in these eyes may cause visual impairment not only because of damage to the optic nerve and deterioration of visual field, but also because of failure of the corneal graft.1 We compared the performance of 3 different tonometers in eyes that underwent PK. Whereas the GAT and Tono-Pen XL are used widely in clinical practice, the ORA is still considered to be contemporary and has not been examined in eyes that have undergone PK in a clinical study. To the best of our knowledge, this is the first study that compares these tonometry techniques in this setting. All IOP readings showed correlation with GAT readings, whereas, not surprisingly, IOPg showed the best correlation. These observations are encouraging and demonstrate that all 3 tonometers are relevant for clinical IOP measurement in eyes that have undergone PK, despite the fact that each technique is based on a different principle and mechanism. When statistically comparing measurements within subjects, GAT resulted in the lowest IOP values. It has been suggested previously that in the presence of corneal edema, GAT may underestimate the true IOP, because the tip immerses into the hydrated tissue and may cause less applanation of the cornea.22–24 Although GAT was found to overestimate IOP in normal but thick corneas,13,14,25–28 it may be that true IOP in eyes that have undergone PK is even lower. Interestingly, in our study, CCT did not correlate to GAT measurements, neither AMERICAN JOURNAL
IOPcc – GAT (51) IOPg – GAT (51) Tono-Pen XL – GAT (49)
Significancea
GAT ⫽ Goldmann applanation tonometer; IOPcc ⫽ cornealcompensated intraocular pressure; IOPg ⫽ Goldmann-correlated intraocular pressure. a Paired t test with Bonferroni correction for multiple comparisons. Significance was considered for P ⬍ .005/3.
FIGURE 2. Box-and-whisker plot showing intraocular pressure (IOP). GAT ⴝ Goldmann applanation tonometer (HaagStreit, Bern, Switzerland); IOPcc ⴝ corneal-compensated IOP; IOPg ⴝ Goldmann-correlated IOP.
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FIGURE 3. Graph showing the correlation between central corneal thickness (CCT) and corneal-compensated intraocular pressure (IOPcc), Goldmann-correlated IOP (IOPg), Tono-Pen XL (Reichert Inc, Depew, New York, USA), and Goldmann applanation tonometer (GAT; Haag-Streit, Bern, Switzerland).
By using the paired t test with Bonferroni correction for multiple comparisons, we found that IOPcc resulted in the highest values, followed by Tono-Pen XL IOP, and finally IOPg and GAT IOP, with no significant difference between the 2 latter tonometry techniques. In a recent study of eyes with normal corneas by Sullivan-Mee and associates, the authors found that IOPcc values were significantly higher than GAT IOP measurements, which, similarly to our findings, did not differ from IOPg measurements.29 Mollan and associates showed, in a similar manner to ours, that IOP measured with Tono-Pen XL in normal eyes was significantly higher than that measured with the GAT.30 Furthermore, the authors showed that GAT readings were significantly different for all measures except IOPg. In a study by Touboul and associates, IOPg and IOPcc were found to differ significantly from GAT IOP measurements in normal corneas too, but in contrast to findings by Mollan and associates, no difference was found between IOPcc and IOPg.30,31 These inconsistencies make it difficult to compare our findings in eyes that have undergone PK with those of previous studies performed on normal eyes. In any case, eyes that have undergone PK probably comprise a stand-alone biomechanical entity, and therefore extrapolations from studies on normal eyes are of limited value. Mean IOP measured by the Tono-Pen XL was higher than that of the GAT, and no significant correlation was found between the Tono-Pen XL and CCT, similar to GAT. These findings support previous studies of normal and eyes that have undergone PK in which the Tono-Pen XL was shown to overestimate IOP compared with GAT, although it was independent of CCT.26,32,33 Several studies examined the Tono-Pen XL with eyes that underwent VOL. 151, NO. 5
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PK and concluded that it is an appropriate tool in cases in which GAT is not applicable.17,34 Findings from our study support this conclusion. Tono-Pen XL IOP measurements were shown to correlate inversely to the follow-up time between the PK procedure and our study. We found no support for this finding in the literature. Because IOP measurements taken in our study were obtained at a single time point, on different subjects, with varying time after PK surgery, to clarify this issue further, a prospective study in which IOP measurements are obtained from a single subject over time is necessary. As expected, CH was found to correlate inversely with IOPcc, because it is related to the calculation of IOPcc. No other correlations were exhibited between CH and any of the other tonometry techniques. In contrast, Tono-Pen XL and IOPg were found to correlate significantly with CRF. Interestingly, when performing a multivariate analysis in which all 3 corneal biomechanical factors (ie, CCT, CH, and CRF) were included, CCT had no influence, whereas CH and CRF played a role, although one must be cautious in interpreting correlations with IOPcc and IOPg that are derived from the same parameters of P1 and P2 as CH and CRF. Findings from our study suggest that CRF may be of importance when measuring IOP in eyes that have undergone PK, because it correlates with independent measures of IOP, whereas CCT is of no considerable contribution. Additional studies should be performed to clarify this concept. Ten (16.39%) of 61 eyes with poor vision resulting from poor fixation were excluded from the study, because the ORA failed to measure IOP in these eyes. This is a major limitation of the instrument in a population in which approximately 20% of grafts fail after 3 years of follow-up, resulting in extreme deterioration of visual acuity.35 Theses subjects were measurable with other tonometric technologies that did not require fixation, including the GAT and Tono-Pen XL. We can speculate that the ORA would fail to measure IOP in any case with ocular pathologic features resulting from poor fixation, and this, of course, limits its clinical use. This study has its limitations. For comparison, we used the GAT as the gold standard, but one may ask whether it is indeed the tonometer with which to compare in eyes after PK. McMillan and Forster found the MacKay-Marg tonometer, which is not in routine clinical use, to approximate manometric measurements most closely in edematous corneas of owl monkey eyes, whereas the GAT was significantly different from true IOP.23 No comparative studies on human eyes that have undergone PK have been reported between manometric measurements and GAT up to now. Others have suggested that any condition that alters corneal shape and thickness may cause uncertainties in GAT measurements.25,26,28 Furthermore, the Tono-Pen XL, which has a smaller transducer area than the GAT (1.2 mm vs 3.06 mm) was suggested to be more accurate in eyes that have undergone AFTER
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TABLE 4. Relationship between Corneal Biomechanical Characteristics and Intraocular Pressure Measurements using the Ocular Response Analyzer, Goldmann Applanation Tonometer, and Tono-Pen XL in Eyes after Penetrating Keratoplasty
Relationship with (R)
Goldmann Applanation Tonometer
CCT CH CRF Regression analysis (R2)
0.085 –0.041 0.256 —
Ocular Response Analyzer IOPcc
IOPg
Tono-Pen XL
0.141 –0.463a –0.085 22.486 – 3.365CH ⫹ 2.765CRFb (0.914)
–0.102 0.202 0.557b 11.684 – 2.742CH ⫹ 3.101CRFb (0.888)
–0.039 0.117 0.368a 13.985 – 1.610CH ⫹ 1.793CRFb (0.422)
— ⫽ a regression analysis could not be obtained for Goldmann Applanation Tonometer; CCT ⫽ central corneal thickness; CH ⫽ corneal hysteresis; CRF ⫽ corneal resistance factor; IOPcc ⫽ corneal compensated intraocular pressure; IOPg ⫽ Goldmann-correlated intraocular pressure. a P ⬍ .01. b P ⬍ .001.
PK.17,34 Nevertheless, GAT is still considered the gold standard for IOP measurements and is the most widespread tonometer in clinical use. To minimize the effect of diurnal variation in IOP, we performed all measurements in an interval of 2 hours. Nevertheless, we cannot rule out that such an effect still may have occurred and may have caused a systematic bias between early and late IOP measurements. Because ORA was used first, this potential flaw may be related specifically to a tonometry technique (ORA versus other tonometers used in the study). Still, we believe that a noncontact examination should be performed before contact ones, because such an examination has less impact on the cornea, and thus on subsequent measurements. Repeating IOP measurements, specifically using contact tonometers, may cause an additional source of error. However, to overcome this potential flaw, contact tonometers (ie, GAT and Tono-Pen XL) were used in a randomized fashion. Because we could not compare IOP measurements with
intracameral manometric measurements, it is impossible to determine which tonometer measures IOP more accurately on the basis of our study. Although limited in its clinical use in cases of poor fixation, ORA provides important information regarding corneal viscoelastic properties in eyes that have undergone PK, enabling a better understanding of the influence of the various factors on transcorneal IOP measurements. CCT seems not to play a role in IOP measurements of eyes that have undergone PK, possibly because of lower elastic modulus. In contrast, CH and especially CRF are probably of significant impact, as shown by regression analysis. GAT IOP measurements, which were lower than those of other tonometer techniques, may underestimate true IOP values in eyes that have undergone PK; however, not having compared the data with intracameral manometry, it may be that other tonometry techniques may overestimate true IOP in this population.
PUBLICATION OF THIS ARTICLE WAS SUPPORTED BY THE BAHAREV FUND FOR GLAUCOMA RESEARCH AND PREVENTION, TEL Aviv University Medical School, Tel Aviv, Israel. The authors indicate no financial conflict of interest. Involved in Design and conduct of study (I.D.F., I.S.B., E.R., M.G., S.M.); Management (I.D.F., I.S.B., S.M.) and analysis, interpretation, and preparation (I.D.F., I.S.B., A.S., E.R., M.G., C.J.R., S.M.) of data; and Review of manuscript (I.D.F., I.S.B., C.J.R., S.M.). The Sheba Hospital, Tel Hashomer Institutional Review Board approval was obtained to conduct this study.
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23. McMillan F, Forster RK. Comparison of MacKay-Marg, Goldmann, and Perkins tonometers in abnormal corneas. Arch Ophthalmol 1975;93(6):420 – 424. 24. Kaufman HE. Pressure measurement: which tonometer? Invest Ophthalmol 1972;11(2):80 – 85. 25. Ehlers N, Bramsen T, Sperling S. Applanation tonometry and central corneal thickness. Acta Ophthalmol (Copenh) 1975;53(1):34 – 43. 26. Johnson M, Kass MA, Moses RA, Grodzki WJ. Increased corneal thickness simulating elevated intraocular pressure. Arch Ophthalmol 1978;96(4):664 – 665. 27. Shah S, Chatterjee A, Mathai M, et al. Relationship between corneal thickness and measured intraocular pressure in a general ophthalmology clinic. Ophthalmology 1999;106 (11):2154 –2160. 28. Whitacre MM, Stein RA, Hassanein K. The effect of corneal thickness on applanation tonometry. Am J Ophthalmol 1993;115(5):592–596. 29. Sullivan-Mee M, Gerhardt G, Halverson KD, Qualls C. Repeatability and reproducibility for intraocular pressure measurement by dynamic contour, ocular response analyzer, and Goldmann applanation tonometry. J Glaucoma 2009; 18(9):666 – 673. 30. Mollan SP, Wolffsohn JS, Nessim M, et al. Accuracy of Goldmann, ocular response analyser, Pascal and TonoPen XL tonometry in keratoconic and normal eyes. Br J Ophthalmol 2008;92(12):1661–1665. 31. Touboul D, Roberts C, Krautret J, et al. Correlations between corneal hysteresis, intraocular pressure, and corneal central pachymetry. J Cataract Refract Surg 2008;34(4): 616 – 622. 32. Hansen FK, Ehlers N. Elevated tonometer readings caused by a thick cornea. Acta Ophthalmol (Copenh) 1971;49(5): 775–778. 33. Geyer O, Mayron Y, Loewenstein A, Neudorfer M, Rothkoff L, Lazar M. Tono-Pen tonometry in normal and in postkeratoplasty eyes. Br J Ophthalmol 1992;76(9):538 –540. 34. Shemesh G, Waisbourd M, Varssano D, Michaeli A, Lazar A, Kurtz S. Measurements of intraocular pressure by Goldmann tonometry, Tonopen XL, and the transpalpebral tonometer, TGDc-01, after penetrating keratoplasty: a comparative study. Cornea 2009;28(7):724 –727. 35. Beckingsale P, Mavrikakis I, Al-Yousuf N, Mavrikakis E, Daya SM. Penetrating keratoplasty: outcomes from a corneal unit compared to national data. Br J Ophthalmol 2006; 90(6):728 –731.
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surements obtained using the Goldmann applanation tonometer (GAT; Haag-Streit), the Tono-Pen XL (Reichert, Inc), and the ocular response analyzer (ORA; Reichert Ophthalmic Instruments), and to determine the influence of corneal factors on IOP measurements in eyes that had undergone penetrating keratoplasty (PK). ● DESIGN: Consecutive, prospective study. ● METHODS: Study population. Sixty-one eyes that underwent PK were enrolled in this study. Intervention. IOP was measured using the GAT, Tono-Pen, and ORA. Corneal hysteresis and corneal resistance factor as provided by the ORA were recorded. Central corneal thickness was measured using an ultrasound pachymeter. Main outcome measures. IOP and corneal biomechanical factors. ● RESULTS: IOP measurements were obtained in an average of 65 months (range, 6 to 209 months) after PK surgery. ORA-derived IOP measurements (corneal-compensated IOP and Goldmann-correlated IOP) and TonoPen XL IOP all correlated in a significant manner to GAT IOP measurements. Corneal-compensated IOP and Tono-Pen XL IOP values were higher than GAT IOP (P < .001 and P ⴝ .001, respectively), whereas Goldmann-correlated IOP readings did not differ from GAT IOP readings (P ⴝ .054). Central corneal thickness did not correlate to any tonometry technique. In a regression analysis, corneal hysteresis and corneal resistance factor were found to play a role in IOP prediction. ● CONCLUSIONS: Central corneal thickness may be of less importance than corneal hysteresis and corneal resistance factor in IOP determination in eyes that have undergone PK, perhaps because of the lower modulus of elasticity in these eyes. GAT IOP seems to be lower than other tonometry techniques in eyes that have undergone PK. (Am J Ophthalmol 2011;151:774 –781. © 2011 by Elsevier Inc. All rights reserved.) Accepted for publication Nov 9, 2010. From the Goldschleger Eye Institute, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (I.D.F., I.S.B., A.S., E.R., M.G., S.M.); and the Department of Ophthalmology and Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio, USA (C.J.R.). Inquiries to Ido D. Fabian, Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer 52621, Israel; e-mail: [email protected]
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elevated intraocular pressure (IOP) in eyes that have undergone penetrating keratoplasty (PK) is very important, because increased IOP in these patients may cause progressive endothelial cell loss and eventually may lead to transplant failure.1 In addition, glaucoma is considered to be one of the most common causes for irreversible visual loss in eyes that have undergone PK.2 However, diagnosis of glaucoma after PK is a major clinical problem because of inconsistency in IOP measurements caused by graft irregularities,3 thick or astigmatic corneal graft, and irregular corneal surface epithelium.4 Patients who have undergone PK are prone to glaucoma development because of distortion of the angle, collapse of the trabecular meshwork, or peripheral anterior synechiae formation, which was found to be the main cause for late-onset post-PK glaucoma.5,6 Further causes may be steroid-induced glaucoma, development of postoperative inflammation, or pre-existing glaucoma. Occurrence of glaucoma in patients who have undergone PK was shown to be higher compared with that in the general population, with a rate of up to 14% in the immediate postoperative phase and up to nearly 30% in the long term.2,7–10 An early and accurate detection of increased IOP in eyes that have undergone PK therefore is crucial not only to preserve the optic nerve and to prevent functional visual field loss, but also to maintain the survival of the corneal graft. Several tonometers are available for the measurement of IOP in clinical practice. The Goldmann applanation tonometer (GAT; Haag-Streit, Bern, Switzerland), which is considered the gold standard tonometer in clinical practice for normal corneas, may be less accurate in eyes that have undergone PK, because it was shown to be influenced by various parameters, such as central corneal thickness (CCT), corneal curvature, and cornea structure.11–16 The Tono-Pen XL (Reichert, Inc, Depew, New York, USA) is a hand-held instrument based on the MacKayMarg principle that uses a microstrain gage technology and a small transducer tip used for applanation of the cornea. The Tono-Pen XL was shown to be less affected by CCT and ocular surface abnormalities compared with GAT, as
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0002-9394/$36.00 doi:10.1016/j.ajo.2010.11.007
TABLE 1. Intraocular Pressure and Corneal Biomechanical Readings in Eyes after Penetrating Keratoplasty
Ocular response analyzer IOPcc IOPg Goldmann applanation tonometer Tono-Pen XL Central corneal thickness Corneal hysteresis Corneal resistance factor
No. Eyes
Mean (mm Hg)
SD (mm Hg)
Range (mm Hg)
51 51 51 49 50 51 51
16.8 15.1 14.2 15.9 585.9a 9.5 9.5
4.1 4.2 4.4 3.5 86.2a 2.8 3.0
7.9 to 27.8 8.1 to 27.1 5.5 to 26.5 8.3 to 24.3 470.0 to 796.0a 4.6 to 17.7 4.8 to 18.3
IOPcc ⫽ corneal-compensated intraocular pressure; IOPg ⫽ Goldmann-correlated intraocular pressure; SD ⫽ standard deviation. a Micrometers.
demonstrated in eyes that underwent PK and that underwent epikeratophakia.17 The Reichert ocular response analyzer (ORA; Reichert Ophthalmic Instruments, Buffalo, New York, USA) is a novel noncontact tonometer that uses a rapid air pulse and an electro-optical system to record 2 applanation pressure measurements: one while the cornea moves inward (P1) and the other in the outward direction (P2), while the cornea returns to its normal state. The average of the 2 measurements provides the Goldmann-correlated IOP (IOPg) value. Corneal-compensated IOP (IOPcc) is a linear combination of P1 and P2 that is empirically derived to be less sensitive to errors related to corneal properties, when compared with other tonometry techniques18,19 (Luce D. IOVS 2006;47:E-abstract 2266). A new viscoelastic parameter known as corneal hysteresis (CH) was defined, which is the difference of the 2 applanation pressure measurements. The ORA also provides an additional viscoelastic parameter that was designed empirically to have maximal correlation with central corneal thickness, which is the corneal resistance factor (CRF; Luce D. IOVS 2006;47:E-abstract 2266). The aim of this study was to compare IOP measurements obtained by the GAT, the Tono-Pen XL, and the ORA in eyes that had undergone PK and to investigate the influence of biomechanical parameters, including CH, CRF, and CCT, on IOP measurement using these 3 common tonometer technologies.
METHODS THE STUDY WAS PERFORMED IN A PROSPECTIVE MANNER
from May 2009 through October 2009. Patients eligible for the study were subjects who underwent PK for various corneal pathologic characteristics at least 6 months before the current study and were followed-up at the Cornea Clinic at Goldschleger Eye Institute. Subjects were excluded from the analysis if measurements, using the ORA VOL. 151, NO. 5
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were not obtainable because of poor fixation, rejected grafts, or significant corneal edema. Subjects were given an empty envelope, with which they moved from one examination station to another through a predesigned course. Each parameter was recorded on a designed sheet, which was given to the subject and sealed in the envelope. After going through all examination stations, the envelope was delivered to one of the authors (I.D.F.), who copied all data to a case report form. Each of the 3 IOP-measuring technologies was implemented by a single different observer (one of the authors) who was masked to previous IOP measurements to reduce interoperator bias. To minimize the potential confounding effect of diurnal variation in IOP, all measurements were obtained in the morning between 9 and 11 am, with a 10-minute interval between readings. All tonometers were calibrated according to manufacturer’s guidelines. Measurements with the ORA were obtained first, before instillation of topical corneal anesthesia to avoid decrease in IOPcc, as previously reported.20 Up to 4 measurements were obtained, and the result with the highest waveform score was used for analysis to obtain IOPcc, IOPg, CH, and CRF parameters. After ORA examination, a corneal topography scan (Keratron Corneal Analyzer; Optikon 2000, Rome, Italy) was performed followed by ultrasonic pachymetry measurements (Altair Ultrasonic Pachymeter; Optikon 2000). The mean of 3 readings was recorded as the CCT value. IOP measurements using the GAT and Tono-Pen XL subsequently were obtained in a randomized fashion. Using the GAT, an average between the horizontal and the vertical measurement was used to overcome highly astigmatic corneas, as described previously.21 A total of 3 consecutive measurements were obtained and averaged. For Tono-Pen XL measurements, a disposable cap was used for each subject and an average of 3 measurements was used for analysis. We accepted only values with a coeffiAFTER
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TABLE 2. Intraocular Pressure and Corneal Structural Factors of Eyes after Penetrating Keratoplasty with and without Corneal Sutures 95% Confidence Interval of the Difference
Intraocular pressure measurements Ocular response analyzer IOPcc IOPg Goldmann applanation tonometer Tono-Pen XL Corneal biomechanical factors Central corneal thickness Corneal hysteresis Corneal resistance factor
Presence of Corneal Sutures
Mean Value (mm Hg)
Significance (2-tailed)a
Upper
Lower
⫹ – ⫹ – ⫹
16.34 17.19 14.88 15.32 13.93
0.463
–3.17
1.46
0.711
–2.81
1.93
0.631
–3.10
1.90
– ⫹ –
14.53 15.41 16.34
0.360
–2.93
1.08
⫹ – ⫹ – ⫹ –
579.41b 593.57b 9.87 9.16 9.82 9.19
0.568
–63.66b
35.35b
0.380
–0.90
2.33
0.471
–1.11
2.36
⫹ ⫽ corneal sutures are present; – ⫽ corneal sutures are not present; IOPcc ⫽ corneal-compensated intraocular pressure; IOPg ⫽ Goldmann-correlated intraocular pressure. a Micrometers. b t Test, equal variances assumed.
surements and IOP measured by all other tonometers. A P value less than .05/3 ⫽ 0.0167 was considered significant.
cient of variation (standard deviation divided by the mean) of 5% or less. In addition, all subjects underwent a routine ophthalmologic examination, including best-corrected visual acuity, slit-lamp examination of the anterior segment, and fundus examination. Axial length measurements were performed with an ultrasonic biometer (model 820; Allergan, Humphrey, San Leandro, California, USA). Data regarding demographics, corneal basic pathologic features, surgical details, and current medical treatment were retrieved from the medical records and analyzed.
RESULTS A TOTAL OF 61 EYES OF 51 PATIENTS WHO UNDERWENT PK
were enrolled in our study. Of these, 10 eyes (16.39%) of 9 patients with best-corrected visual acuity of hand movements or worse were excluded because they could not fixate on the signaling light inside the ORA instrument. The cohort comprised 22 males and 20 females, with a mean age of 54 ⫾ 19 years (range, 18 to 91 years). The original diseases were keratoconus (n ⫽ 23), stromal dystrophies (n ⫽ 4), stromal opacity occurring after herpes keratitis (n ⫽ 9), stromal opacity occurring after bacterial or fungal corneal abscesses (n ⫽ 6), penetrating injuries (n ⫽ 4), and pseudophakic bullous keratopathy (n ⫽ 5). Measurements for our study were obtained in a mean time of 65 ⫾ 41 months after PK surgery (range, 6 to 209 months). Fourteen eyes (27.45%) had also a diagnosis of glaucoma before the enrollment in the study and were treated with topical antiglaucoma medication. Using the Tono-Pen XL for 2 subjects, measurements could not
● STATISTICAL ANALYSIS: All calculations were performed and presented using Microsoft Excel 2003 (Microsoft Corporation, Redmond, Washington, USA) and SPSS software version 15.0 (SPSS, Inc, Chicago, Illinois, USA). The Pearson correlation was used to assess the dependence of the different tonometry techniques on corneal biomechanical parameters (ie, CCT, CH, and CRF). Multivariate analyses were undertaken to predict IOP measurements, taking into account the aforementioned parameters (ie, demographic, operative, and postoperative data). The level of significance was chosen at P ⬍ .05. The Paired t test with Bonferroni correction for multiple comparisons was used to assess the differences between GAT IOP mea776
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FIGURE 1. Graphs showing correlations between intraocular pressure (IOP) measured by (Top left) the Goldmann applanation tonometer (GAT; Haag-Streit, Bern, Switzerland) and corneal-compensated IOP (IOPcc), R2 ⴝ 0.4351 (P < .001); (Top right) Goldmann-correlated IOP (IOPg), R2 ⴝ 0.5239 (P < .001); and (Bottom) the Tono-Pen XL (Reichert, Inc Depew, New York, USA), R2 ⴝ 0.363 (P < .001).
be obtained. Table 1 lists the IOPs as measured by each of the 3 tonometers. Twenty-eight (54.90%) eyes had graft sutures still present at the time of measurements. No significant statistical difference was found in IOP measurements of eyes with or without corneal sutures using the various tonometry techniques, as shown in Table 2. In the same manner, no significant difference was found in the values of the structural corneal factors (ie, CCT, CH, and CRF) when subdividing into eyes with corneal sutures and without (Table 2). The mean keratometry readings were 47.92 diopters (D; range, 37.42 to 59.50 D) and 41.92 D (range, 30.22 to 49.02 D) for the steep and flat meridians, respectively. The mean corneal astigmatism was 5.88 D (range, 0.00 to 18.02 D). No correlation was found between IOP, corneal biomechanical factors, or time gap between corneal transplant surgery and measurements and corneal curvature measurements (P ⱖ .08). All IOP measurements were found to correlate in a significant manner with GAT IOP measurements, with IOPg measured by the ORA displaying the highest correlation (R2 ⫽ 0.5239, P ⬍ .001; Figure 1). The distribution of IOP is shown in box-and-whisker plots for each tonomVOL. 151, NO. 5
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etry technique used (Figure 2). IOPcc measurements were the highest, followed by the Tono-Pen XL. Both were significantly different from GAT measurements, whereas IOPg did not differ from GAT, as shown in Table 3. The Tono-Pen XL was the only tonometer that inversely correlated, in a significant manner, to the time gap between PK surgery and measurements performed during our study (Pearson correlation, ⫺0.395; P ⫽ .006). IOP measurements using all other tonometers did not correlate significantly to the time from PK surgery and the present study. CCT, CH, and CRF results are shown in Table 1. Mean CCT was 585.92 ⫾ 86.18 m (range, 470.00 to 769.00 m). CCT did not correlate significantly to any of the tonometers (Figure 3). Furthermore, CCT did not correlate to any of the tonometry techniques even after subdividing the cohort to 2 subgroups, above and beneath the median CCT measure (550 m). Table 4 shows the relationship between the corneal biomechanical characteristics, that is, CCT, CH, and CRF, and the different tonometry techniques. CH was inversely related to IOPcc, whereas all other tonometry techniques were not influenced by CH. CRF correlated in a significant manner to IOPg and Tono-Pen XL only (Table 4). AFTER
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TABLE 3. Differences between Average Intraocular Pressure Values Measured by the Ocular Response Analyzer (IOPcc and IOPg) and the Tono-Pen XL and Intraocular Pressure Measured by the Goldmann Applanation Tonometer
2.52 0.88 1.76
P ⬍ .001 P ⫽ .054 P ⫽ .001
when analysis of the entire cohort study was performed nor when compared with a subgroup of eyes with CCT of 550 m or less. Medeiros and Weinreb compared GAT and ORA tonometry in normal eyes and found that the tonometers differed in a significant manner in relation to CCT: patients with thicker corneas tended to have higher GAT IOP measurements compared with IOPcc, whereas in patients with thin corneas, GAT IOP measurements tended to be lower than IOPcc.18 However, comparison of findings based on measurements in normal eyes with the eyes in the current study probably is irrelevant, because CCT was shown not to correlate to any of the tonometry techniques in eyes that underwent PK. It is interesting that although none of our cases displayed corneal edema at the time of measurement, GAT IOP still gave the lowest value. We can speculate that parameters other than CCT and corneal edema contribute to this measurement in PK eyes. It has been shown in a theoretical analysis that corneal biomechanical properties, specifically modulus of elasticity, has a greater effect on GAT measurement error than CCT.16 In fact, it was shown further that the elastic modulus determines the relationship of GAT measurement error to CCT, with stiffer corneas of higher modulus having a stronger relationship to CCT than softer corneas with a lower modulus. Because CCT was shown to have no correlation to tonometry in the current study and GAT measurements were lower than those of other techniques, this may suggest that corneas that have undergone PK have lower elastic modulus than normal corneas. This may not be reflected in the CH or CRF parameters, which are viscoelastic in nature and respond to changes in both elasticity and viscosity. No difference was found in IOP, CCT, CH, or CRF values between corneas with and without sutures (Table 2); therefore, no correction factor is needed when measuring these parameters in eyes that have undergone PK with regard to the presence or absence of corneal sutures.
DISCUSSION MEASURING IOP IN AN ACCURATE MANNER IS OF GREAT
importance, especially in eyes that are prone to elevated IOP developing, such as eyes that have undergone PK.2,7–10 Delay in detection and treatment of elevated IOP in these eyes may cause visual impairment not only because of damage to the optic nerve and deterioration of visual field, but also because of failure of the corneal graft.1 We compared the performance of 3 different tonometers in eyes that underwent PK. Whereas the GAT and Tono-Pen XL are used widely in clinical practice, the ORA is still considered to be contemporary and has not been examined in eyes that have undergone PK in a clinical study. To the best of our knowledge, this is the first study that compares these tonometry techniques in this setting. All IOP readings showed correlation with GAT readings, whereas, not surprisingly, IOPg showed the best correlation. These observations are encouraging and demonstrate that all 3 tonometers are relevant for clinical IOP measurement in eyes that have undergone PK, despite the fact that each technique is based on a different principle and mechanism. When statistically comparing measurements within subjects, GAT resulted in the lowest IOP values. It has been suggested previously that in the presence of corneal edema, GAT may underestimate the true IOP, because the tip immerses into the hydrated tissue and may cause less applanation of the cornea.22–24 Although GAT was found to overestimate IOP in normal but thick corneas,13,14,25–28 it may be that true IOP in eyes that have undergone PK is even lower. Interestingly, in our study, CCT did not correlate to GAT measurements, neither AMERICAN JOURNAL
IOPcc – GAT (51) IOPg – GAT (51) Tono-Pen XL – GAT (49)
Significancea
GAT ⫽ Goldmann applanation tonometer; IOPcc ⫽ cornealcompensated intraocular pressure; IOPg ⫽ Goldmann-correlated intraocular pressure. a Paired t test with Bonferroni correction for multiple comparisons. Significance was considered for P ⬍ .005/3.
FIGURE 2. Box-and-whisker plot showing intraocular pressure (IOP). GAT ⴝ Goldmann applanation tonometer (HaagStreit, Bern, Switzerland); IOPcc ⴝ corneal-compensated IOP; IOPg ⴝ Goldmann-correlated IOP.
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FIGURE 3. Graph showing the correlation between central corneal thickness (CCT) and corneal-compensated intraocular pressure (IOPcc), Goldmann-correlated IOP (IOPg), Tono-Pen XL (Reichert Inc, Depew, New York, USA), and Goldmann applanation tonometer (GAT; Haag-Streit, Bern, Switzerland).
By using the paired t test with Bonferroni correction for multiple comparisons, we found that IOPcc resulted in the highest values, followed by Tono-Pen XL IOP, and finally IOPg and GAT IOP, with no significant difference between the 2 latter tonometry techniques. In a recent study of eyes with normal corneas by Sullivan-Mee and associates, the authors found that IOPcc values were significantly higher than GAT IOP measurements, which, similarly to our findings, did not differ from IOPg measurements.29 Mollan and associates showed, in a similar manner to ours, that IOP measured with Tono-Pen XL in normal eyes was significantly higher than that measured with the GAT.30 Furthermore, the authors showed that GAT readings were significantly different for all measures except IOPg. In a study by Touboul and associates, IOPg and IOPcc were found to differ significantly from GAT IOP measurements in normal corneas too, but in contrast to findings by Mollan and associates, no difference was found between IOPcc and IOPg.30,31 These inconsistencies make it difficult to compare our findings in eyes that have undergone PK with those of previous studies performed on normal eyes. In any case, eyes that have undergone PK probably comprise a stand-alone biomechanical entity, and therefore extrapolations from studies on normal eyes are of limited value. Mean IOP measured by the Tono-Pen XL was higher than that of the GAT, and no significant correlation was found between the Tono-Pen XL and CCT, similar to GAT. These findings support previous studies of normal and eyes that have undergone PK in which the Tono-Pen XL was shown to overestimate IOP compared with GAT, although it was independent of CCT.26,32,33 Several studies examined the Tono-Pen XL with eyes that underwent VOL. 151, NO. 5
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PK and concluded that it is an appropriate tool in cases in which GAT is not applicable.17,34 Findings from our study support this conclusion. Tono-Pen XL IOP measurements were shown to correlate inversely to the follow-up time between the PK procedure and our study. We found no support for this finding in the literature. Because IOP measurements taken in our study were obtained at a single time point, on different subjects, with varying time after PK surgery, to clarify this issue further, a prospective study in which IOP measurements are obtained from a single subject over time is necessary. As expected, CH was found to correlate inversely with IOPcc, because it is related to the calculation of IOPcc. No other correlations were exhibited between CH and any of the other tonometry techniques. In contrast, Tono-Pen XL and IOPg were found to correlate significantly with CRF. Interestingly, when performing a multivariate analysis in which all 3 corneal biomechanical factors (ie, CCT, CH, and CRF) were included, CCT had no influence, whereas CH and CRF played a role, although one must be cautious in interpreting correlations with IOPcc and IOPg that are derived from the same parameters of P1 and P2 as CH and CRF. Findings from our study suggest that CRF may be of importance when measuring IOP in eyes that have undergone PK, because it correlates with independent measures of IOP, whereas CCT is of no considerable contribution. Additional studies should be performed to clarify this concept. Ten (16.39%) of 61 eyes with poor vision resulting from poor fixation were excluded from the study, because the ORA failed to measure IOP in these eyes. This is a major limitation of the instrument in a population in which approximately 20% of grafts fail after 3 years of follow-up, resulting in extreme deterioration of visual acuity.35 Theses subjects were measurable with other tonometric technologies that did not require fixation, including the GAT and Tono-Pen XL. We can speculate that the ORA would fail to measure IOP in any case with ocular pathologic features resulting from poor fixation, and this, of course, limits its clinical use. This study has its limitations. For comparison, we used the GAT as the gold standard, but one may ask whether it is indeed the tonometer with which to compare in eyes after PK. McMillan and Forster found the MacKay-Marg tonometer, which is not in routine clinical use, to approximate manometric measurements most closely in edematous corneas of owl monkey eyes, whereas the GAT was significantly different from true IOP.23 No comparative studies on human eyes that have undergone PK have been reported between manometric measurements and GAT up to now. Others have suggested that any condition that alters corneal shape and thickness may cause uncertainties in GAT measurements.25,26,28 Furthermore, the Tono-Pen XL, which has a smaller transducer area than the GAT (1.2 mm vs 3.06 mm) was suggested to be more accurate in eyes that have undergone AFTER
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TABLE 4. Relationship between Corneal Biomechanical Characteristics and Intraocular Pressure Measurements using the Ocular Response Analyzer, Goldmann Applanation Tonometer, and Tono-Pen XL in Eyes after Penetrating Keratoplasty
Relationship with (R)
Goldmann Applanation Tonometer
CCT CH CRF Regression analysis (R2)
0.085 –0.041 0.256 —
Ocular Response Analyzer IOPcc
IOPg
Tono-Pen XL
0.141 –0.463a –0.085 22.486 – 3.365CH ⫹ 2.765CRFb (0.914)
–0.102 0.202 0.557b 11.684 – 2.742CH ⫹ 3.101CRFb (0.888)
–0.039 0.117 0.368a 13.985 – 1.610CH ⫹ 1.793CRFb (0.422)
— ⫽ a regression analysis could not be obtained for Goldmann Applanation Tonometer; CCT ⫽ central corneal thickness; CH ⫽ corneal hysteresis; CRF ⫽ corneal resistance factor; IOPcc ⫽ corneal compensated intraocular pressure; IOPg ⫽ Goldmann-correlated intraocular pressure. a P ⬍ .01. b P ⬍ .001.
PK.17,34 Nevertheless, GAT is still considered the gold standard for IOP measurements and is the most widespread tonometer in clinical use. To minimize the effect of diurnal variation in IOP, we performed all measurements in an interval of 2 hours. Nevertheless, we cannot rule out that such an effect still may have occurred and may have caused a systematic bias between early and late IOP measurements. Because ORA was used first, this potential flaw may be related specifically to a tonometry technique (ORA versus other tonometers used in the study). Still, we believe that a noncontact examination should be performed before contact ones, because such an examination has less impact on the cornea, and thus on subsequent measurements. Repeating IOP measurements, specifically using contact tonometers, may cause an additional source of error. However, to overcome this potential flaw, contact tonometers (ie, GAT and Tono-Pen XL) were used in a randomized fashion. Because we could not compare IOP measurements with
intracameral manometric measurements, it is impossible to determine which tonometer measures IOP more accurately on the basis of our study. Although limited in its clinical use in cases of poor fixation, ORA provides important information regarding corneal viscoelastic properties in eyes that have undergone PK, enabling a better understanding of the influence of the various factors on transcorneal IOP measurements. CCT seems not to play a role in IOP measurements of eyes that have undergone PK, possibly because of lower elastic modulus. In contrast, CH and especially CRF are probably of significant impact, as shown by regression analysis. GAT IOP measurements, which were lower than those of other tonometer techniques, may underestimate true IOP values in eyes that have undergone PK; however, not having compared the data with intracameral manometry, it may be that other tonometry techniques may overestimate true IOP in this population.
PUBLICATION OF THIS ARTICLE WAS SUPPORTED BY THE BAHAREV FUND FOR GLAUCOMA RESEARCH AND PREVENTION, TEL Aviv University Medical School, Tel Aviv, Israel. The authors indicate no financial conflict of interest. Involved in Design and conduct of study (I.D.F., I.S.B., E.R., M.G., S.M.); Management (I.D.F., I.S.B., S.M.) and analysis, interpretation, and preparation (I.D.F., I.S.B., A.S., E.R., M.G., C.J.R., S.M.) of data; and Review of manuscript (I.D.F., I.S.B., C.J.R., S.M.). The Sheba Hospital, Tel Hashomer Institutional Review Board approval was obtained to conduct this study.
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pressure after keratoplasty. Invest Ophthalmol Vis Sci 1977;16(12):1085–1092. Lass JH, Pavan-Langston D. Timolol therapy in secondary angle-closure glaucoma post penetrating keratoplasty. Ophthalmology 1979;86(1):51–59. Kirkness CM, Ficker LA. Risk factors for the development of postkeratoplasty glaucoma. Cornea 1992;11(5):427– 432. Ing JJ, Ing HH, Nelson LR, Hodge Do, Bourne WM. Ten-year postoperative results of penetrating keratoplasty. Ophthalmology 1998;105(10):1855–1865. Redbrake C, Arend O. [Corneal transplantation and glaucoma]. Ophthalmologe 2000;97(8):552–556.
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