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Test–retest variability of intraocular pressure and ocular pulse amplitude for dynamic contour tonometry: a multicentre study
  1. P Fogagnolo1,
  2. M Figus2,
  3. P Frezzotti3,
  4. M Iester4,
  5. F Oddone1,
  6. M Zeppieri5,
  7. A Ferreras6,
  8. P Brusini5,
  9. L Rossetti7,
  10. N Orzalesi7
  1. 1GB Bietti Foundation—IRCCS, Rome, Italy
  2. 2Eye Clinic, Department of Neuroscience, University of Pisa, Pisa, Italy
  3. 3Dipartimento di Scienze oftalmologiche e Neurochirurgiche, Universita' degli Studi di Siena, Siena, Italy
  4. 4Clinica Oculistica, Università di Genova, Genoa, Italy
  5. 5Azienda Ospedaliero-Universitaria, S Maria della Misericordia di Udine, SOC di Oculistica, Udine, Italy
  6. 6Department of Ophthalmology, Miguel Servet University Hospital, University of Zaragoza, Zaragoza, Spain
  7. 7Eye Clinic, Department of Medicine, Surgery and Dentistry, San Paolo Hospital, University of Milan, Milan, Italy
  1. Correspondence to Dr Paolo Fogagnolo, Eye Clinic, San Paolo Hospital, Via di Rudini' 8, 20142 Milan, Italy; fogagnolopaolo{at}googlemail.com

Abstract

Aims To assess the test–retest variability of intraocular pressure (IOP) and ocular pulse amplitude (OPA) measurements utilising dynamic contour tonometry (DCT) and to evaluate possible influential factors.

Methods The study included 350 consecutive subjects (175 glaucoma, 175 control; one eye per subject) from seven European centres. IOP was measured once with a Goldmann applanation tonometer (GAT) and twice by DCT (DCT1, DCT2) in a randomised sequence. OPA was also recorded for both DCT measurements. Differences (DCT1-DCT2; OPA1-OPA2; GAT-DCT1; GAT-DCT2) were assessed using the t test. The intraclass coefficient of correlation (ICC) and coefficient of variation (CoV) for DCT and OPA were calculated.

Results DCT1 was 0.6±1.6 mm Hg higher than DCT2 (p<0.001); OPA1 was 0.1±0.7 mm Hg higher than OPA2 (p=0.02). Results were not influenced by randomisation test order. In both glaucoma and normal subjects, DCT and OPA showed ICC>0.90 and >0.76, and CoV=4.8–5.0% and 10.3–10.5%, respectively. DCT1 and 2 were 2.4±2.6 and 1.8±2.6 mm Hg higher respectively than GAT (p<0.001).

Discussion DCT test–retest variability was almost perfect for IOP and good for OPA. Tonometry measurements with DCT tended to be overestimated compared with GAT.

  • Tonometry
  • intraocular pressure (IOP)
  • reproducibility
  • primary open-angle glaucoma (POAG)
  • ocular pulse amplitude

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Introduction

Goldmann applanation tonometry (GAT) has been the gold standard for assessing intraocular pressure (IOP) since 1957.1 A number of factors, however, have been shown to affect GAT measurements, which include the type tonometry utilised and physical ocular properties (ie, corneal thickness, corneal curvature, astigmatism, axial length).2 3 In recent years, tonometric instruments with automated readings have been developed with the aim of providing IOP readings that are minimally influenced by individual eye characteristics. The Pascal dynamic contour tonometer (DCT, Swiss Microtechnology AG, Port, Switzerland) is a relatively new tonometer and has provided good preliminary clinical results.

The DCT was designed to provide IOP measurements that are not affected by corneal properties thanks to the shape of the silicon cover, which matches the contour of the cornea causing minimal distortion while taking the IOP readings. The measurement is based on the interface forces between the tip and the cornea that counterbalance the force distribution generated by the IOP. When contact between these two structures is obtained, a sensor embedded in the tip provides IOP measurements transcorneally.4 5

Studies on human cadaver eyes have shown that DCT provided a better accuracy than GAT.6 7 Similar findings have also been reported in patients who underwent corneal refractive surgery.8 Boehm et al has recently shown convincing evidence that DCT measurements have a good concordance with the ‘true’ manometric IOP taken by intracameral cannulation during cataract surgery.9

In addition to IOP measurements, DCT also provides an ocular pulse amplitude (OPA), defined as the difference between systolic and diastolic IOP during the period of contact between the tonometer and eye (whereas IOP is defined as the mean of systolic and diastolic values). OPA is indicative of ocular blood flow and might prove to be an important parameter in the clinical management of glaucoma.10 11

Numerous studies have dealt with DCT, but little has been reported on the reproducibility and variability of DCT measurements,12–16 especially on patients with primary open-angle glaucoma (POAG) using a multicentre approach. The aim of our study was to assess the test–retest variability (TRV) of IOP and OPA by DCT in normal and POAG subjects, and to determine whether the sequence of measurements and eye parameters has an influence on DCT readings.

Materials and methods

This prospective observational cross-sectional randomised study involved seven European sites: Genoa, Milan, Pisa, Rome, Siena, Udine (Italy) and Zaragoza (Spain). The study was in adherence to the tenets of the Declaration of Helsinki, and informed signed consent for research was obtained from each subject before enrolment.

Patient selection

This study included one eye from 350 consecutive subjects from June to October 2008, including 175 normal subjects and 175 patients with POAG, whose characteristics are given in table 1. Each of the seven centres consecutively recruited 25 normal and 25 POAG patients. One eye per subject was randomly selected if both eyes met the inclusion criteria. Normal eyes were recruited from hospital staff, relatives and normal subjects undergoing routine refraction examination. POAG patients were recruited from the Department of Ophthalmology Glaucoma Clinics.

Table 1

Demographics and ophthalmic characteristics of normal and glaucoma subjects

The inclusion criteria were: best-corrected visual acuity (BCVA) of 20/30 or better; no previous intraocular surgery (ie, cataract or refractive surgery); 18 years of age or older; and transparent ocular media (lens opacity <1 according to the Lens Opacities Classification System III system).17 The exclusion criteria were: normal tension glaucoma; history of ocular surgery, corneal pathology or contact lens use; secondary causes of glaucoma; significant media opacities; and neurological disorders. All participants underwent a full ophthalmological examination to confirm diagnosis, which included: medical history, biomicroscopy, gonioscopy, GAT (Haag-Streit International, Koniz, Switzerland) and indirect fundus ophthalmoscopy. SAP testing was performed using the Humphrey Field Analyser (HFA) II 750 (Carl Zeiss Meditec, Dublin, California) 24-2 or 30-2 test with Standard Swedish Interactive Threshold Algorithm (SITA) strategy. POAG eyes were defined as having: IOP >21 mm Hg prior to medication, glaucomatous optic neuropathy (if at least one of the following was evident: optic nerve head excavation, undermining of the neural rim; notching involving ≥2 clock hours; focal or diffuse atrophy of neural rim area involving ≥2 clock hours; disc haemorrhage; focal or generalised atrophy of the nerve fibre layer) and repeatable abnormal visual-field results using standard automated perimetry. During the study, all POAG patients were receiving medical treatment to reduce IOP. Control subjects were defined as having an IOP ≤21 mm Hg, no ocular pathologies, and normal optic disc appearance and visual-field results.

Study procedures

Each subject enrolled in the study underwent the following, in respective order: keratometry and biometry by optical biometry system (IOL Master; Carl Zeiss AG, Feldbach, Switzerland), subjective refraction, BCVA, IOP measurements and pachimetry. IOP readings were always taken before other contact examinations.

DCT and GAT IOP measurements were taken with instillation of oxybuprocaine 0.4% drops and fluoresceine strip. Each eye underwent three IOP measurements (with a 5 min break between testing) using one of the following sequences:

  1. DCT1, DCT2, GAT;

  2. DCT1, GAT, DCT2;

  3. GAT, DCT1, DCT2.

The principal investigator (PF) generated a randomisation list of the sequences (by means of a list of random numbers) common to all centres. When an eligible subject was enrolled in the study, the site contacted the principal investigator, who sent the randomisation code.

Central corneal thickness (CCT) was then measured with an ultrasonic pachymeter (SP-3000, CBD Ophthalmic/TOMEY, Phoenix, Arizona) by positioning the probe on the centre of the cornea. The mean CCT value was calculated based on three readings within a range of ±5 μm.

IOP measurements

All centres were given specific details regarding the study protocol and were instructed to respect the standard operating procedures for IOP measurement approved by the European Vision Institute. Investigators tested intraobserver variability for DCT and GAT before the study (κ-statistics applied to at least 50 measurements on five patients and confirmed it to be >0.80). All measurements were obtained by a single experienced investigator per site. During measurement, the investigators made every effort to reduce or eliminate any possible source of avoidable variability.

Goldmann applanation tonometry

At each centre, the same tonometer was used throughout the study, and this instrument was calibrated at the beginning of each session. GAT was measured after the application of topical anaesthetic drops with fluoresceine. Measurement was the mean of two readings within 2 mm Hg or, if the difference was >2 mm Hg, the median of three measurements. The examinator, who measured IOP by GAT, was instructed not to read the value, which was collected by a second operator.

Dynamic contour tonometry

DCT is used in a similar fashion to GAT, in that topical anaesthetic drops with fluoresceine are applied. The DCT tip (which has a disposable silicone cover) is then positioned on the centre of the cornea. The correct positioning on the cornea is confirmed by an audible regular flickering signal that changes in pitch. According to manufacturer recommendations, a correct IOP measurement is obtained by interrupting the coupling procedure after at least seven consecutive pulsations of the audible regular flickering signal. DCT automatically generates the following three values: IOP, OPA and Q-value (qualitative score of measurement: Q=1, optimum; Q=2 or 3, acceptable; Q=4, questionable; Q=5, low quality). In accordance with the manufacturer recommendations, IOP measurements were repeated for low-quality measurements of Q>3. This occurred once in 8% of the readings and twice in 2% of the time in our cohort of subjects.

Statistical analysis

The analysis was performed with SPSS (V.13.0; SPSS Science, Chicago, Illinois). IOP and OPA measurements were expressed as mean±SD. The t test was used for comparisons; p≤0.05 was considered significant. The agreement between GAT and DCT readings was assessed with the Bland–Altman method, in which the differences between readings were plotted with the mean measurements.18 The coefficient of variation (CoV) and coefficient of repeatability (CoR) were used to assess TRV for DCT measurements.18 The intraclass correlation coefficient (ICC) was used to assess reproducibility for DCT measurements.19 20 Agreement was judged as: perfect if ICC=1; almost perfect 0.81 to 0.99; substantial 0.61 to 0.80; moderate 0.41 to 0.60; fair 0.21 to 0.40; slight 0.01 to 0.20; and poor –1 to 0. Multiple regression analysis was used to assess the influence of ocular structural factors (CCT, CC, AL), age, diagnosis, DCT quality score and ophthalmological centre on the measurement differences. Interobserver differences in test–retest variability for DCT (IOP and OPA) were evaluated by analysis of variance (ANOVA), and in the case of significant results, data pairs were inspected by t test.

Results

The main results of the study are shown in tables 2–4. IOP readings with both GAT and DCT were significantly higher (p≤0.0001) in glaucoma patients than in controls; the first OPA reading was similar in the two groups, whereas the second was higher in the glaucoma group (p=0.03; table 2). In the entire cohort, DCT1 and DCT2 were respectively 2.39±2.63 and 1.79±2.55 mm Hg higher than GAT (p<0.0001; figure 1), DCT1 was 0.59±1.55 mm Hg higher than DCT2 (p<0.0001); OPA1 was 0.09±0.72 mm Hg higher than OPA2 (p=0.02). No differences were found between glaucoma and normal subjects, except for OPA2 (which was higher in glaucoma patients; p=0.03) and for the difference between OPA1 and OPA2 (which was higher in controls; p=0.02). The measurement sequence did not have a significant effect on results (tables 3 and 4).

Table 2

Mean data on intraocular pressure and ocular pulse amplitude

Table 3

Effect of sequence on the whole study population

Table 4

Coefficient of variability, repeatability and intraclass coefficient of correlation

Figure 1

Bland–Altman plots for (A) the first measurement using dynamic contour tonometry (DCT1) and Goldmann applanation tonometry (GAT) and (B) the second measurement using DCT (DCT2) and GAT.

The CoVs found in the entire cohort were: 5.0% for DCT (range: 4.1 to 5.5%) and 10.4% for OPA (range: 8.5 to 11.6%), which corresponded to CoR of 3.24 (range: 2.90 to 4.05) and 1.42 (range: 1.09 to 2.08) mm Hg respectively. The variability and repeatability did not change significantly for the analysis on subgroups (table 4).

The reproducibility of DCT measurements was almost perfect (ICC range: 0.86 to 0.96) when subjects were assessed as a whole or in subgroups (glaucoma, normals or any sequence); it was substantial when glaucoma patients were assessed based on the study randomisation sequence (ICC>0.62). The reproducibility of OPA was almost perfect (ICC=0.84) for the cohort as a whole; however, it was substantial to almost perfect (range: 0.64 to 0.82) for the subgroup analysis.

Multiple regression analysis showed that the only parameter that had a significant influence on the difference between DCT and GAT was CCT (DCT–GAT=9.397−0.01283×CCT, p=0.0006, regression analysis).

The interobserver test–retest variability for OPA was negligible (p=0.76, F=0.57<2.12, 6 degrees of freedom), whereas it was statistically significant for DCT (p=0.01, F=2.86>2.12, 6 degrees of freedom), with one site having a higher variability than two sites (p=0.002 and 0.006). It is noteworthy that the seven populations had different demographics (age), ophthalmic characteristics (CCT, refraction, biometry, and stage of the disease, ie, MD) and mean, SD and range of GAT, DCT1&2, OPA1&2, DCT1–GAT, DCT2–GAT (p<0.001 for each parameter, ANOVA).

Discussion

Our analysis shows that IOP measurements with DCT are highly reproducible in both glaucoma patients and controls (CoV of 5.0% and ICC>0.90). Most studies to date have reported DCT reproducibility on a normal cohort. Kaufmann et al found that the reproducibility of DCT was higher than GAT (1.11 vs 2.38) in eight normal eyes.15 Another study reported a similar reproducibility between the DCT and GAT on a group of 50 normal eyes undergoing four repeated measurements with each tonometer.14 Herdener et al found that the difference in normal eyes with a high IOP difference (>2 mm Hg) between DCT and GAT was reproducible.13 Further studies reported a strong correlation (r=0.93) between two consecutive DCT measurements on 323 normal subjects.16 Erdurmus et al recently reported a high DCT reproducibility (ICC=0.92) in a cohort of glaucoma patients, which was based on six DCT repeated measurements by two operators on a group of 30 POAG and 11 OH eyes.12

To the best of our knowledge, the reproducibility of OPA has been reported in only two studies. The first study showed a strong reproducibility in normal subjects,16 while the second study reported a variability ranging from 7.6% to 9.5% in a cohort of POAG, OH and control eyes.21 Our study shows a slightly higher variability of about 10% with a substantial ICC, in which no differences were found between control and glaucoma eyes.

The coefficient of repeatability for DCT measurements was also part of our analysis. This parameter has a high clinical relevance because it provides the CIs outside which measurements should be repeated, because they are likely affected by external factors and not only by inherent variation.

IOP collection is more time-consuming and difficult for DCT than GAT;22 therefore, in clinical settings, DCT should be considered as a complementary instrument to measure IOP, rather than a substitute for GAT. Considering that the two instruments are used in series, the aim of our study was also to address the influence of the sequence of acquisition, and we showed that the sequence order did not have a significant influence on measurements. Overall, the mean DCT was 1.6–2.5 mm Hg higher than GAT, showing negligible differences between sequences and between normal and glaucoma subjects. This is in contrast to previous studies that reported a larger difference in healthy23 and glaucomatous eyes24 respectively.

The relationship between CCT and IOP measurement is complex and incompletely characterised, and this limits the clinical interpretation of GAT and DCT measurements.24 In light of the contrasting results regarding the influence of CCT on DCT,24–26 our multiple regression analysis suggested that CCT had a significant influence on the difference between GAT and DCT, with a 0.1 mm Hg decrease for every 10 μm increase in CCT (based on our formula, the difference between the two tonometers would be null for CCT=732 μm).

Few studies suggested that IOP-lowering drops might influence CCT measurements. This change is supposed to be small, but it might influence high IOP values so that subtle differences might be noted.27 As our protocol did not require CCT information pre- and post-treatment, the study was not controlled for this potential problem.

Apart from OPA, test–retest variability for DCT was significant; yet, it should be noted that this finding could reflect not only variability per se, but also differences in the characteristics of the seven populations, which actually had different demographics and ocular characteristics.

Despite the almost perfect ICC and the very good CoV of DCT, our study showed that DCT2 was significantly lower than DCT1 in all groups by a mean of 0.6 mm Hg, which has not been previously reported. Viestenz et al assessed the IOP of control eyes using a sequence of three repeated DCT measurements, followed by two applanation measurements and another DCT measurement.16 The authors found a good reproducibility between the first two DCT measurements, however; the third DCT reading was significantly lower than the first by 0.4 mm Hg. This ‘tonographic effect’ was not observed between the third DCT measurement and the last (after the two GAT measurements). When assessing the raw data sets from all centres, there appeared to be trend towards a slight ‘tonographic effect’ over repeat measurements; however, the multiple regression analysis showed that sequence order was not significant. DCT may have an applanation-like effect that can cause slightly lower retest measurements; however, further biophysical and biomechanical ocular studies are needed. In closing, IOP and OPA measurements with DCT are highly reproducible in both normal and glaucoma subjects and are unaffected by sequence of measurements. DCT can thus be clinically useful as a complementary instrument to GAT, providing IOP confirmation and OPA, which may prove to be clinically useful.

Acknowledgments

We are very grateful to M L Salvetat (Udine) for the patient data collection, statistical assessment of the results and scientific revision of the manuscript. We also thank S Puccio (Milan), A Tosto (Rome), S Peruzzi (Siena), C Tosoni and L Parisi (Udine), for their valuable support in patient recruitment, testing and data collection.

References

Footnotes

  • Preliminary results presented at ARVO, Fort Lauderdale, USA, 3–7 May 2009.

  • Competing interests None.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.