Breaking Point

Put simply, a stable tear film protects the ocular surface epithelium from drying. When the tear film components are insufficient or impaired, the tear film breaks up, resulting in dry eye disease (DED). Tear film breakup is a core mechanism of dry eye, and abnormal breakup time and symptoms are considered part of the diagnostic criteria for dry eye. Thus, tear film-oriented diagnostic methods based on the tear film breakup patterns are considered essential for the diagnosis of DED (1). TFBUT – which has become the standard diagnostic procedure for DED – measures the interval of time that elapses between a complete blink and the appearance of the first break in the tear film. Short breakup time has become widely recognized as a major contributor to DED in recent years (2); indeed, more attention is now paid to unstable tear films than to the tear volume or superficial punctate keratopathy (3). According to the Tear Film and Ocular Surface Society Dry Eye Workshop II (TFOS DEWS II), TFBUT is the most frequently employed test of tear film stability in clinical practice (4). 

But TFBUT does not consider the blinking rate. Blinking spreads the tear film, mucin, and lipids on the cornea and conjunctiva, maintaining the eye’s moisture and protecting the eye from irritants (5, 6). Notably, blink rates – measured as interblink interval (IBI, the mean time between two blinks) – are found to differ between normal participants and patients with DED (6). As IBI correlates with clinical characteristics of DED (7), it should therefore be considered as one of the parameters for its diagnosis. The Ocular Protection Index (OPI) was developed to overcome the disadvantages of TFBUT by measuring multiple causative factors of DED (8); however, it is not being used in routine clinical practice because of a lack of awareness among eyecare professionals. 

Here, we highlight why the OPI is a better measure than TFBUT alone, explore OPI research and its use in clinical trials, and discuss how OPI can be used in routine clinical practice.

Why OPI?
DED is caused by a lower tear production rate and/or a short tear film stable time. The ocular surface becomes dry and lacks lubrication, eventually damaging the ocular surface (9). A short TFBUT is a key factor for the diagnosis of DED (10), with a cut-off value of less than 10 seconds. 

But the preservation of a stable tear film over the ocular surface also depends on spontaneous eye blinking, in addition to the amount of tear secretion and lipid quality. Spontaneous blinking is a rapid, automatic, and unconscious opening and closing of the eyelids – unlike reflex and voluntary blinking (11). The process is critical for spreading the tear film over the ocular surface, lipid secretion into the tear film, and tear drainage, and it is essential for maintaining optical quality. Unfortunately, spontaneous blinking is affected by both age and mental activity. Stimulation of the ocular surface increases the spontaneous blinking rate, while reduced blinking rate is associated with increasing tear film evaporation and the development of DED. Blinking rate is both a cause and a consequence of DED (12).

In healthy patients, the mean IBI (the time between two blinks) is approximately 7.5 seconds (13). Note that it is the interaction between tear film stability and IBI that maintains the health of the ocular surface, so the number of seconds quantifying TFBUT does not provide pathophysiologic information to completely understand the nature and severity of the case of dry eye. The OPI was developed to quantify the interaction between blinking and the tear film and is simply a ratio of TFBUT and IBI (TFBUT divided by IBI). An OPI score <1.0 indicates an exposed ocular surface, which leads to the development or exacerbation of the signs and symptoms of dry eye. An OPI score >1.0 indicates a tear-protected ocular surface, potentially resulting in fewer dry eye signs and symptoms (13).

The advantage of OPI is that it measures two components involved in DED. The disadvantages of OPI are i) TFBUT has to be measured using fluorescein dye (such staining is invasive; the TFOS DEWS II Diagnostic Methodology Subcommittee prefers measurement of the tear breakup time with a non-invasive technique – NIBUT), and ii) the IBI measurement must be performed at a different time (13).

OPI research: a brief history
The concept of OPI was first introduced by Ousler and colleagues in 2002 when they were trying to understand the factors that influence the IBI – and the relationship between IBI and TFBUT. In the study, subjects underwent baseline examinations including visual acuity, ocular discomfort (0-4 scale), and blink rate. Complete blinks were measured non-invasively using a digital micro-camera equipped with an infrared illuminator mounted to a headset extension and directed towards the eye. Subjects were placed in a controlled adverse environment (CAE) for 90 minutes. During CAE exposure, blink rate was measured every 10 minutes while ocular discomfort was recorded every five minutes. The mean blink rate increased significantly from 11 blinks/minute pre-CAE to 20 blinks/minute post-CAE. The mean ocular discomfort also increased significantly from 0.63-units pre-CAE to 2.38 units post-CAE. Ultimately, the study showed that the OPI quantifies the relationship between TFBUT and the IBI and is useful in assessing dry eye and the effect of its therapeutic agents (15).

Not only has the OPI been used to validate new screening/diagnostic methods (17, 18), it has also been used in ocular surface disease index questionnaires as a discriminative test for clinical findings in DED patients (17). The OPI was also employed along with other diagnostic tests for DED to investigate the utility of tear osmolarity measurement in the diagnosis of DED (18).

The OPI has also been used in some clinical trials evaluating the efficacy of artificial tears and topical antihistamines/mast cell stabilizers for the treatment of DED (19, 20, 21, 22). Osuler and colleagues measured the efficacy of Systane Ultra, Refresh Tears, and Refresh Endura using the OPI in 59 patients with DED. The OPI score was significantly greater in DED patients who received Systane Ultra at 15 and 30 minutes versus Refresh Tears. The OPI score was also significantly higher in the Systane Ultra group when compared with the Refresh Endura group at five minutes. The author attributed the higher OPI score to the unique mechanism of action of the Systane Ultra formulation (20). In another study, it was used as a tool to study the risk of damage to the ocular surface by a fixed topical combination of brinzolamide 1% plus timolol 0.5% suspension versus dorzolamide 2% plus timolol 0.5% solution, both preserved with benzalkonium chloride in patients with primary open-angle glaucoma (23).

Clinical application of OPI
The OPI can be used as a tool to identify patients at risk of developing signs and symptoms associated with dry eye. And it is also useful as a tool for educating patients about the interaction between tear film integrity and their blinking patterns to help develop conscious blinking. The index also provides a reliable means of measuring clinically significant changes that result from artificial tears or therapeutic agents on ocular surface protection (13). In terms of research, it can be used to validate new screening/diagnostic methods, to study the risk of damage to the ocular surface by anti-glaucoma medication, as a parameter to screen patients for inclusion in clinical trials, and to quantify the therapeutic effect of artificial tears on DED (13).

DED can only be diagnosed appropriately by evaluating the changes in different components of tear film integrity. Although TFBUT is a recognized method of diagnosis of DED, it does not take the role of blinking into account. The OPI quantifies the interaction of tear film integrity and the blinking process, therefore offering a better indication of ocular surface health than TFBUT alone. The OPI has proven to be a useful and clinically relevant tool when it comes to the diagnosis of DED in routine clinical practice – and we believe it is worth integrating into your own clinic.