When assessing glaucoma risk, measuring intraocular pressure (IOP) and examining visual fields and optic disc appearance have all been standard practice for many years. These results do not tell us the whole story though. Assessment of anterior chamber angles has added to our understanding of the eye’s architecture (see Optician 20.05.16) and its associated glaucoma risk, and optical coherence tomography (OCT) assessment of nerve fibre layer thickness has furthered our knowledge of the retinal changes in pre-perimetric glaucoma. While we have added some layers of complexity to these assessments we can sometimes ignore the accuracy of our most basic measurement in the glaucoma detection toolbox- tonometry.
Tonometry limitations
The gold standard for IOP measurement (Goldmann applanation tonometry-GAT) works by applanating an area of the central cornea. Applanation tonometry is based on the Imbert-Fick principle, which states that the pressure inside a thin-walled sphere equals the force necessary to flatten its surface divided by the area of flattening. In applanation tonometry, the cornea is flattened and the IOP is determined by varying the applanating force until the area flattened is 3.06mm in diameter.1 With this area of applanation, the forces offered by corneal rigidity are offset by the opposing surface tension action of the tears.
Both the assumption of a ‘thin-walled sphere’ and a set corneal rigidity can lead us to see where the potential inaccuracies are in measurement. How thin is thin? Is every cornea as rigid, or are some more so than others? Does increased thickness always mean increased rigidity?
Measuring the central corneal thickness (CCT) can allow us to increase the accuracy of the measurements we are taking. In practice, the instrument most commonly used to measure CCT is a pachymeter. Knowing the CCT of course allows us to answer the ‘thin walled sphere’ question, but does make some assumptions about corneal rigidity. An average CCT is 555µm. Corneas thicker than this are assumed to be more rigid, require greater force to applanate and therefore give a misleadingly high IOP reading. Thinner corneas are assumed to be less rigid and therefore easier to applanate and give a misleadingly low reading. Until the results of the Ocular Hypertension Treatment Study (OHTS) were published we did not fully understand how much of a risk a thinner cornea was.
Ocular hypertension treatment study
The OHTS was a large, multi-centred American study2,3 which published its data in 2002 with some very interesting findings on corneal thickness. The main aim of the study was to identify whether ocular hypertensives should be treated prophylactically before disc damage and visual field loss confirmed a diagnosis of primary open angle glaucoma (POAG).
The study recruited more than 1600 subjects with various recruitment criteria and were randomised into two groups. One group was the observation group (with no drug treatment) and the other was medicated with the aim of reducing their IOP by 20% (to below 24mmHg). At the time of recruitment, all patients underwent a battery of tests to rule out POAG – including confirmation of the presence of reproducible clear full threshold visual fields and healthy optic nerve heads (ONHs). Participants were followed at six-monthly intervals and, if a repeatable visual field defect or damage to the ONH were identified, they were diagnosed with POAG.
Five years from commencement of the study, the difference in progression to POAG was significant between the two groups; 4.4% of those treated and 9.5% of the observation group developed glaucomatous damage.
Digging into the results produced lots of very useful information on risk factors for development of POAG. It could be argued the most valuable of these concerned corneal thickness. At five years, 36% of those who had presented with an IOP of 25.75mmHg or greater and a CCT of less than 555µn went on to develop POAG.
Correspondingly, only 6% of those who presented with the same pressure but CCT thicker than 588µm developed POAG. Similar findings were seen when the study analysed disc appearance and CCT – only 4% with a vertical cup to disc ratio of 0.3 or less and CCT of 588µm or more developed POAG, whereas 15% with the same disc parameters but CCT under 555µm did.
Corneal thickness measures were thus shown to be highly significant for these patients and measurement should now be considered an essential part of our daily clinical practice. Such is the clinical relevance of having a thin CCT, properly assessing a patient’s risk is impossible without knowledge of this measurement.
African-Americans tend to have thinner corneas and only 14% have thicker corneas, in comparison with 27% of Caucasians.5 Without pachymetry this means that we are already underestimating the IOP of patients in this ethnic group. We already know that patients of African origin have a higher risk of glaucoma and from an earlier age, failing to investigate CCT could compound this problem and increase their risk even further.
Studies have shown a reduction in CCT with age four and a thicker CCT in males6 but strong correlations are not often demonstrated. In reality measuring CCT is the only way to definitively know an individual patient’s risk. Diurnal variations have also been shown, with higher CCT overnight.
Pachymetry in clinical practice
Ultrasound contact pachymetry
Unlike assessing anterior chamber angles, or anterior chamber depth, corneal thickness is not a measurement we can get from a slit lamp examination. The gold standard is by ultrasound pachymetry (UP) and various models are available. There are also optical methods of measurement, such as OCT. There are significant differences between the two methods and these should be carefully considered.7
Using an ultrasound pachymeter (eg Pachmate, Pachpen – figure 1) is relatively simple. All ultrasound pachymeters take multiple readings of CCT and average the result. The ultrasound probe (figure 2) has to be placed perpendicularly on the corneal surface, as close to the apex as possible (figure 3). When touching the surface the probe will automatically take a number of readings, giving an audible signal when they are complete. The cornea obviously has to be anaesthetised for this procedure and due to the corneal contact there is a small risk of corneal damage and abrasion. There will be some inter-practitioner variability dependent on skill level but if the operator is comfortable performing applanation tonometry they will likely perfect the use of pachymetry very quickly.
Figure 1: An ultrasound pachymeter takes multiple CCT readings
Once all the readings are taken the operator can view them individually and delete any that are too far from the mean, this further refines the final mean reading which should be reported, along with instrument used and the standard deviation.
Figure 2: An ultrsound probe
Non-contact OCT Pachymetry
OCT measurements of CCT are non-invasive and do not require instillation of anaesthetic. They also do not need to be done by the optometrist (figures 4, 5 and 6). Many studies have been done to assess how accurately OCT measures compare to UP. There is a significant range of findings in this matter, but it is generally accepted that OCT underestimates CCT, giving a false increase in risk and potential over-referral to already busy ophthalmology clinics. As with IOP, it is worth confirming all measurements using the gold standard measure (UP) for accuracy and correlation with ophthalmology examination techniques.
Figure 3: The probe has to be placed perpendicularly on the corneal surface as close to the apex as possible
Using conversion charts with CCT readings
Once you have measured CCT you need to have an understanding of the risk (or otherwise) associated with any particular measurement. Correction charts exist which allow you to adjust the IOP for the measured CCT. There are, however, many problems with this thinking. Various correction factors exist and none precisely agree with each other. All apply a linear model to the correction where it has been shown that, at the higher risk end (patients with higher IOP and thinner corneae), the relationship is not linear. The most common correction models have been published by Ehlers (1975)8 which showed a 5mmHg shift for every 70µm of thickness, Whitacre (Rotterdam Eye Study, 1997)9 which showed 2mmHg for 100µm thickness and Doughty and Zaman (2000)10 which showed 2.5mmHg for 50µm thickness. This last publication was a meta-analysis and has therefore been the most commonly used.
Figure 4: An OCT single scan through the cornea
Pachymeter manufacturers also built these algorithms into their instruments and the correction charts are widely available in print and online. It became common practice to use the charts to correct the applanation reading for CCT, which in itself can pose a risk to the patient unless clinical records are completely clear whether any measurement recorded is the corrected one or not. Understanding what is normal, thin or thick in corneal measurements is a more exact way of using pachymetry to accurately determine risk of glaucoma.
Corneal thickness – what is normal and when is my patient at significant risk?
Rather than using a pachymetry measure to ‘correct’ an IOP it has been suggested by many that we should divide patients into thickness categories to identify their risk of glaucoma. Murray Fingeret (Professor at SUNY College of Optometry) suggests the following categories;
- Very thin <510µm
- Thin <535
- Normal 540-560
- Thick >565
- Very Thick >600
Corneas thinner than 500µm are always a cause for close monitoring due to the significant risk of glaucoma, over 600µm constitutes a very low risk.
It has been considered that a thin cornea correlates to a thin lamina cribrosa: that the posterior structure of the eye is also part of the problem but studies have struggled to definitively prove this.
SIGN 144: Glaucoma referral and safe discharge
The Scottish Intercollegiate Guidelines Network (SIGN) published guidelines on glaucoma in March 2015.11 The guidelines cover all aspects of glaucoma detection including method, refinement and detail of IOP measurement, disc assessment, angle grading, visual field examination and corneal thickness measurement. With robust criteria the guidelines allow us to refine our clinical measures and prevent unnecessary referrals.
Figure 5: OCT corneal radial scan showing a curvature and a thickness map
The SIGN guidelines are research driven and incorporated the findings of the OHTS in respect of CCT. The CCT criteria for referral are very specific.
- Patients who have ocular hypertension with intra-ocular pressure of >25mmHg may be considered for referral to secondary-eye-care services irrespective of corneal thickness.
- Patients who have ocular hypertension with intra-ocular pressure of <26mmHg and central corneal thickness <555µm should be referred to secondary-eye-care services if they are aged </=65.
- Patients who have ocular hypertension with intra-ocular pressure of <26mmHg and central corneal thickness >/=555µm may be monitored in the community.
The guidelines are as accurate and specific in all other aspects of glaucoma detection.
Following their publication, given how essential CCT readings are to our practice the Scottish government funded a pachymeter for all optometry practices in Scotland. This has made a significant difference in the accuracy of referrals, and whilst practices in the rest of the UK have not been in this enviable position it is worth considering purchasing a pachymeter.
Figure 6: OCT may detect changes over time
The accuracy of IOP is a debate which continues and currently the correlation of corneal thickness to rigidity is one which now is being investigated. Instruments which measure corneal hysteresis are available now and will add to the accuracy of our clinical measures. Until hysteresis measures are further understood and become part of our glaucoma detection process corneal thickness is certainly a measure which will ensure we are confident in our clinical management of glaucoma.
Conclusion
Ultra sound pachymetry is a skill well worth perfecting and using. Given the cost of optometric equipment a pachymeter is very likely to be affordable. For patients with a sensitivity to anaesthetic or a fragile corneal epithelium, or for practitioners without access to UP an OCT measure will certainly give an indication of the broad category into which the patient fits. Intra-ocular pressure values should not be corrected; rather corneal thickness values should be used as another quantitative risk factor.
Morven Campbell is clinical services manager for Black and Lizars
References
1 American Academy of Ophthalmology. Basic and Clinical Science Course Section 10: Glaucoma .
2 Brandt JD, Beiser JA, Gordon MO, Kass MA. Central corneal thickness in the ocular hypertension treatment study (OHTS). Ophthalmology. 2001;108:1779-1788.
3 Herndon LW, Weizer JS, Stinnett SS. Central corneal thickness as a risk factor for advanced glaucoma damage. Arch Ophthalmol. 2004;122:17-21.
4 Tayyab A, Masrur A, Afzal F, Iqbal F, Naseem K. Central Corneal Thickness and its Relationship to Intra-Ocular and Epidemiological Determinants. J Coll Physicians Surg Pak 2016 Jun;26(6):494-7
5 Shimmyo M, Ross AJ, Moy A, et al. Intraocular pressure, Goldmann applanation tension, corneal thickness an corneal curvature in Caucasians, Asians, Hispanics and African-Americans. Am J Ophthalmol. 2003;136:603-613.
6 Sng C, Barton K, Kim H, Yuan S, Budenz DL Central Corneal Thickness and its Associations with Ocular and Systemic Factors in an Urban West African Population Am J Ophthalmol 2016 Jul 13
7 Ishibazawa A, Igarashi S, Hanada K, Nagaoka T, Ishiko S, Ito H, Yoshida A. Central Corneal Thickness measurements with Fourier-domain optical coherence tomography versus ultrasonic pachymetry and rotating Scheimpflug camera. Cornea 2011 Jun 30(6) 615-9
8 Ehlers N, Bramsen T, Sperling S. Applanation tonometry and central corneal thickness. Acta Ophthalmol. 1975 (Copehn);53:34-43.
9 Whitacre MM, Stein RA, Hassanein K. The effect of corneal thickness on applanation tonometry. Am J Ophthalmol. 1993;115:592-596.
10 Doughty MJ, Zaman ML. Human corneal thickness and its impact on intraocular pressure measures: a review and meta-analysis approach. Surv Ophthalmol. 2000;44:367-408.
11 SIGN 144- Glaucoma referral and safe discharge, Scottish Intercollegiate Guidance Network, March 2015