Intraocular Pressure Measurements and Biomechanical Properties of the Cornea in Eyes After Penetrating Keratoplasty


To compare intraocular pressure (IOP) measurements 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).


Consecutive, prospective study.


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.


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 Tono-Pen 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 = .001, respectively), whereas Goldmann-correlated IOP readings did not differ from GAT IOP readings ( P = .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.


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.

Accurate diagnosis and follow-up of 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. In addition, glaucoma is considered to be one of the most common causes for irreversible visual loss in eyes that have undergone PK. However, diagnosis of glaucoma after PK is a major clinical problem because of inconsistency in IOP measurements caused by graft irregularities, thick or astigmatic corneal graft, and irregular corneal surface epithelium. 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. 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. 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.

The Tono-Pen XL (Reichert, Inc, Depew, New York, USA) is a hand-held instrument based on the MacKay-Marg 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 demonstrated in eyes that underwent PK and that underwent epikeratophakia.

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 (P 1 ) and the other in the outward direction (P 2 ), 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 P 1 and P 2 that is empirically derived to be less sensitive to errors related to corneal properties, when compared with other tonometry techniques (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.


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 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. 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. 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 coefficient 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.

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 measurements and IOP measured by all other tonometers. A P value less than .05/3 = 0.0167 was considered significant.


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 be obtained. Table 1 lists the IOPs as measured by each of the 3 tonometers.


Intraocular Pressure and Corneal Biomechanical Readings in Eyes after Penetrating Keratoplasty

No. Eyes Mean (mm Hg) SD (mm Hg) Range (mm Hg)
Ocular response analyzer
IOPcc 51 16.8 4.1 7.9 to 27.8
IOPg 51 15.1 4.2 8.1 to 27.1
Goldmann applanation tonometer 51 14.2 4.4 5.5 to 26.5
Tono-Pen XL 49 15.9 3.5 8.3 to 24.3
Central corneal thickness 50 585.9 a 86.2 a 470.0 to 796.0 a
Corneal hysteresis 51 9.5 2.8 4.6 to 17.7
Corneal resistance factor 51 9.5 3.0 4.8 to 18.3

IOPcc = corneal-compensated intraocular pressure; IOPg = Goldmann-correlated intraocular pressure; SD = standard deviation.

a Micrometers.

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 ≥ .08).


Intraocular Pressure and Corneal Structural Factors of Eyes after Penetrating Keratoplasty with and without Corneal Sutures

95% Confidence Interval of the Difference
Presence of Corneal Sutures Mean Value (mm Hg) Significance (2-tailed) a Upper Lower
Intraocular pressure measurements
Ocular response analyzer
IOPcc + 16.34 0.463 –3.17 1.46
IOPg + 14.88 0.711 –2.81 1.93
Goldmann applanation tonometer + 13.93 0.631 –3.10 1.90
Tono-Pen XL + 15.41 0.360 –2.93 1.08
Corneal biomechanical factors
Central corneal thickness + 579.41 b 0.568 –63.66 b 35.35 b
593.57 b
Corneal hysteresis + 9.87 0.380 –0.90 2.33
Corneal resistance factor + 9.82 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.

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 ( R 2 = 0.5239, P < .001; Figure 1 ). The distribution of IOP is shown in box-and-whisker plots for each tonometry 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 .


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), R 2 = 0.4351 ( P < .001); (Top right) Goldmann-correlated IOP (IOPg), R 2 = 0.5239 ( P < .001); and (Bottom) the Tono-Pen XL (Reichert, Inc Depew, New York, USA), R 2 = 0.363 ( P < .001).


Box-and-whisker plot showing intraocular pressure (IOP). GAT = Goldmann applanation tonometer (Haag-Streit, Bern, Switzerland); IOPcc = corneal-compensated IOP; IOPg = Goldmann-correlated IOP.


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

Pair (No. of Eyes) Difference between Tonometry Techniques (mm Hg) Significance a
IOPcc – GAT (51) 2.52 P < .001
IOPg – GAT (51) 0.88 P = .054
Tono-Pen XL – GAT (49) 1.76 P = .001

GAT = Goldmann applanation tonometer; IOPcc = corneal-compensated intraocular pressure; IOPg = Goldmann-correlated intraocular pressure.

a Paired t test with Bonferroni correction for multiple comparisons. Significance was considered for P < .005/3.

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 μm (range, 470.00 to 769.00 μm). 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 μm). 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 ).

Jan 16, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Intraocular Pressure Measurements and Biomechanical Properties of the Cornea in Eyes After Penetrating Keratoplasty

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