Recently, a lot of emphasis with regard to innovations in glaucoma has been placed on those that help with management of the disease, specifically on the surgical side (the MIGS revolution) and the medication side (the recent FDA approval of Rhopressa [Aerie Pharmaceuticals] and Vyzulta [Bausch + Lomb]).

However, it is also important to focus on what is new in glaucoma diagnostics. The three new significant diagnostics that come to mind are IOP home monitoring, OCT angiography (OCTA) and corneal hysteresis (CH). All three of these technologies are exciting and potentially very impactful. CH has significantly changed my everyday clinical practice, while OCTA and home monitoring of IOP are very interesting and will potentially have a growing impact in the coming years.

Here, I outline these novel glaucoma diagnostics techniques.

IOP HOME MONITORING

The idea behind IOP home monitoring centers around the concern that we are only obtaining a one-minute snapshot of a patient’s true IOP during the day and missing out on the IOP throughout the remaining 99% of the patient’s life (maybe 97%, depending on how long the patient waits in your office ...). Perhaps, if we obtain a true idea of the patient’s IOP throughout the day and night, we might have a better understanding of our patient’s disease state and the success of our IOP lowering interventions (medical and surgical).^1-3

Home monitoring empowers patients to get a better understanding of their disease and may allow them to be more engaged. Additionally, if patients can accurately and safely monitor their IOP at home, they may require fewer office visits, which could lead to a more efficient and cost-effective utilization of health-care resources.^4-6 Valero et al performed studies suggesting that the Icare HOME tonometer (Figure 1) provides reproducible IOP values in glaucoma patients.⁷ In their study investigating the accuracy of the Icare HOME, patients cited the Icare HOME’s ease of use (84%), quick to obtain measurements (88%) and comfort (95%).⁸

IOP home monitoring may also provide the patient with a large amount of information that may induce concern, anxiety or an overfixation around obtaining a specific “target” number, although devices that mask the IOP to the patient may induce less anxiety while providing physicians with very valuable information.

In most cases of glaucoma, the key component is the health of the nerve fiber layer and prevention of damage over an extended period of time. While IOP is a major value that we focus on clinically, I am usually more moved to escalate treatment when I see actual loss of nerve tissue or field loss. Studies demonstrating the pattern of diurnal IOP fluctuation may help predict glaucoma progression,⁵ although studies have yet to demonstrate that the use of IOP home monitoring has been effective in slowing or stopping glaucoma progression.

I will continue to follow this area with great interest in the hope that we can accurately and safely obtain 24-hour IOP monitoring in a non-invasive way.

OCT ANGIOGRAPHY

There is little debate as to whether OCT evaluation of the nerve fiber layer and macula has revolutionized the practice of ophthalmology. As such, OCT is nearly ubiquitous in all offices in the United States that treat patients with glaucoma and retinal diseases.

Recently, OCTA has been used to evaluate the microvascular supply of the optic nerve, retina and choroid (Figure 2). The idea is that OCTA may detect compromised or diminished blood perfusion to optic nerve before glaucoma nerve damage occurs.^9-11 Given that many of these images can be obtained with the OCT hardware currently in most of our offices, this technology has the potential to be rapidly incorporated into daily practice once the software improves and is more readily available. Initial studies have demonstrated that loss of peripapillary retinal vascular density is correlated with glaucomatous damage.^12,13 The hope is that OCTA may give us clinical insights into compromised vascular perfusion of ganglion cells prior to cell death.

Given that hardware to perform OCTA is readily available and the software is rapidly improving, I feel this technology will be rapidly incorporated and potentially very powerful for further elucidating the true pathogenesis of various glaucomas as well as for monitoring glaucoma clinically. The question that remains is what to do with this information. If we can detect early-on that the optic nerve has impaired blood supply, would IOP lowering actually alter blood flow patterns or change retinal vascular density?

I envision OCTA providing us with tremendous insights into the underlying pathogenesis of various forms of glaucoma and enhancing our understanding of the disease process. Moreover, I hope that this new knowledge will subsequently open up more avenues for treatment and intervention.

CORNEAL HYSTERESIS

While this technology is by no means new or novel, recent high quality data confirms the importance of CH in the practical clinical management of glaucoma. As a medical student, I was involved in one of the first studies more than 13 years ago describing an association between CH and visual field progression.¹⁴ Nearly five years ago, I incorporated CH into my daily clinical practice. I now consider this value to be a “glaucoma vital sign” and use it on a daily basis to risk stratify my glaucoma patients (and glaucoma suspects) and help further tailor/individualize follow up for each patient.

CH is a specific output from the Ocular Response Analyzer (ORA, Reichert). In addition to the CH value, ORA provides a corneal compensated IOP (IOPcc) measurement that is useful in certain challenging situations. I will briefly provide an overview of CH and review some pertinent studies that provide evidence for the clinical use of CH in monitoring glaucoma development as well as glaucoma progression.

CH is the only in-vivo measurement of the corneal and ocular biomechanics of the eye. While the exact method for measuring CH is beyond the scope of this article, one can read the exact details in several peer-reviewed articles.^15-18 Clinically, the way I explain CH to my patients is that CH reflects an eye’s shock-absorbing ability. Based on several well-designed randomized prospective trials, we know that eyes that are “good shock absorbers” (high CH) are less likely to develop and progress with glaucoma. Alternatively, eyes that are bad shock absorbers (low CH) are more likely to develop and progress with glaucoma. The thought is that CH reflects how an eye responds to stress (elevated IOP) and whether it absorbs the brunt of the stress (low CH, ie, bad shock absorber) or is able to dissipate the energy and somehow “protect” the eye and the optic nerve from the stress.

Regardless of the theory as to why CH is correlated with glaucoma development and progression, we know a few things: First, the CH population average for most ethnicities is around 10; second, eyes with a CH above 10 are less likely to get and progress with glaucoma; and finally, eyes with a CH lower than 10 are more likely to get and progress with glaucoma.^15-18

Medeiros et al were one of the first groups to demonstrate, in a well-designed prospective clinical trial, that baseline CH has a significant effect on the rate of visual field progression over time in patients with a known diagnosis of glaucoma.¹⁹ Specifically, this group found that eyes with a CH ≥10 did not have any rapidly progressive visual field loss over time; however, in the eyes with a CH <10, there were several cases of rapid progression, all else being equal. This study also demonstrated that, for eyes with lower CH, the impact of IOP was significantly larger than in eyes with higher CH. In fact, in the multivariate model, CH was more than three times more associated with an increased rate of visual field progression than central corneal thickness. Numerous other studies have also reported similar findings along this line.^14,16,18

Moreover, Susanna et al followed up with another study demonstrating that CH is associated with an increased risk of developing glaucoma. In this study, the mean CH of all eyes was 10.2. The authors found that eyes with a CH ≥10.2 had a cumulative probability of developing glaucoma of around 0.1 at five years, whereas the group with a mean CH of <10.2 had a cumulative probability of developing glaucoma of nearly 0.3 at five years. Most impressive is that these were patients followed, monitored and treated by a glaucoma specialist over a five-year period.²⁰

Interestingly (and very clinically useful) is the output from the ORA (Figure 3), which, in addition to a CH measurement, also reveals a predicted Goldmann applanation value (the value that the machine predicts one’s Goldmann applanation will read) as well as an IOPcc, a Goldmann-correlated IOP measurement that is calculated using a patented algorithm intended to minimize the influence of corneal properties. While I personally do not put a lot of weight in the ORA Goldmann applanation value, I feel the CH value and the IOPcc are essential for caring for my patients with glaucoma or at risk for glaucoma.

CH helps me improve the quality of glaucoma care I provide by better risk stratifying my patients and tailoring my treatment of the patient and their eye’s shock-absorbing ability. Several studies have demonstrated that CH is an independent risk factor for glaucoma progression. The evidence suggests that CH is reflective of overall ocular tissue properties and provides insight into the biomechanical principles of the eye. Moreover, CH appears to be related to pressure-independent mechanisms involved in glaucoma pathogenesis and associated changes to the optic nerve. Lastly, IOPcc has been found to be extremely useful in patients with progressive glaucoma despite relatively low IOPs on Goldman applanation. Interestingly, a recent prospective study found that IOPcc was more predictive of glaucomatous visual field progression than Goldmann applanation.²¹

Despite all this information, you still find me dusting off my Goldmann applanation tip every morning. Luckily, we are able to incorporate all of these measurements in our clinical decision-making processes. OM

REFERENCES

1. Liu JH, Zhang X, Kripke DF, Weinreb RN. Twenty-four-hour intraocular pressure pattern associated with early glaucomatous changes. Invest Ophthalmol Vis Sci. 2003;44:1586-1590.
2. Hughes E, Spry P, Diamond J. 24-hour monitoring of intraocular pressure in glaucoma management: a retrospective review. J Glaucoma. 2003;12:232-236.
3. Sit AJ. Continuous monitoring of intraocular pressure: rationale and progress toward a clinical device. J Glaucoma. 2009;18:272-279.
4. Ittoop SM, SooHoo JR, Seibold LK, Mansouri K, Kahook MY. Systematic review of current devices for 24-h intraocular pressure monitoring. Adv Ther. 2016;33:1679-1690.
5. Sood V, Ramanathan US. Self-monitoring of intraocular pressure outside of normal office hours using rebound tonometry: Initial clinical experience in patients with normal tension glaucoma. J Glaucoma. 2016;25:807-811.
6. Takagi D, Sawada A, Yamamoto T. Evaluation of a New Rebound Self-tonometer, Icare HOME: Comparison With Goldmann Applanation Tonometer. J Glaucoma. 2017 Jul;26:613-618.
7. Valero B, Fénolland JR, Rosenberg R, et al. [Reliability and reproducibility of introcular pressure (IOP) measurement with the Icare Home rebound tonometer (model TA022) and comparison with Goldmann applanation tonometer in glaucoma patients] [Article in French]. J Fr Ophtalmol. 2017;40:865-875. doi: 10.1016/j.jfo.2017.06.008. Epub 2017 Nov 22.
8. Dabasia PL, Lawrenson JG Murdoch IE. Evaluation of a new rebound tonometer for self-measurement of intraocular pressure. Br J Ophthalmol. 2015. doi:10.1136/bjophthalmol-2015-307674
9. Liu L, Jia Y, Takusagawa HL, et al. Optical coherence tomography angiography of the peripapillary retina in glaucoma. JAMA Ophthalmology. 2015;133:1045-1052.
10. Yarmohammadi A, Zangwill LM, Diniz-Filho A, et al. Optical coherence tomography angiography vessel density in healthy, glaucoma suspect, and glaucoma eyes. Invest Ophthalmol Vis Sci. 2016;57:OCT451-459.
11. Yarmohammadi A, Zangwill LM, Diniz-Filho A, et al. Peripapillary and macular vessel density in patients with glaucoma and single-hemifield visual field defect. Ophthalmology. 2017;124:709-719.
12. Chen HS, Liu CH, Wu WC et al. “Optical Coherence Tomography Angiography of the Superficial Microvasculature in the Macular and Peripapillary Areas in Glaucomatous and Healthy Eyes.” Invest Ophthalmol Vis Sci. 2017 Jul 1;58:3637-3645.
13. Yarmohammadi A, Zangwill LM, Manalastas PIC, et al. Peripapillary and macular vessel density in patients with primary open-angle glaucoma and unilateral visual field loss. Ophthalmology. 2018;125:578-587.
14. Congdon NG, Broman AT, Bandeen-Roche K, Grover D, Quigley HA. Central corneal thickness and corneal hysteresis associated with glaucoma damage. Am J Ophthalmol. 2006;141:868-875.
15. Luce DA. Determining in vivo biomechanical properties of the cornea with an ocular response analyzer. J Cataract Refract Surg. 2005;31:156-162.
16. Shah S, Laiquzzaman M, Cunliffe, Mantry S. The use of the Reichert ocular response analyser to establish the relationship between ocular hysteresis, corneal resistance factor and central corneal thickness in normal eyes. Cont Lens Anterior Eye. 2006;29:257-262.
17. Murphy ML, Pokrovskaya, O, Galligan M and O’Brien C. Corneal hysteresis in patients with glaucoma-like optic discs, ocular hypertension and glaucoma. BMC Ophthalmology. 2017;17:1
18. De Moraes CVG, Hill V, Tello C, Liebmann JM, Ritch R. Lower corneal hysteresis is associated with more rapid glaucomatous visual field progression. J Glaucoma. 2012;21:209-213.
19. Medeiros FA, Meira-Freitas D, Lisboa R, Kuang T-M, Zangwill LM, Weinreb RN. Corneal hysteresis as a risk factor for glaucoma progression: a prospective longitudinal study. Ophthalmology. 2013;120:1533-1540.
20. Susanna CN, Diniz-Filho A, Daga FB et al. A Prospective Longitudinal Study to Investigate Corneal Hysteresis as a Risk Factor for Predicting Development of Glaucoma. Am J Ophthalmol. 2018 Mar;187:148-152.
21. Susanna BN, Ogata NG, Daga FB et al. Association between Rates of Visual Field Progression and Intraocular Pressure Measurements Obtained by Different Tonometers. Ophthalmology. 2019 Jan;126:49-54.
22. Gillmann K, Mansouri K. Optical Coherence Tomography Angiography for Glaucoma Diagnosis and Follow-Up. Glaucoma Physician. 2018 Dec:16-21.

About the Author