Cookies

Like most websites The Ophthalmologist uses cookies. In order to deliver a personalized, responsive service and to improve the site, we remember and store information about how you use it. Learn more.
Subspecialties Cornea / Ocular Surface, Imaging & Diagnostics

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. 

Blinking rate is both a cause and a consequence of DED.

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).

Determining the OPI
IBI is measured by dividing 60 by the number of blinks per minute (preferably counted while an ECP is taking history, either during routine patient conversation or while the patient reads the vision chart). Next, TFBUT is measured by instilling fluorescein onto the inferior bulbar conjunctival surface using a moistened fluorescein-impregnated paper and having the subject blink several times to mix the fluorescein dye with their tear film. After two controlled blinks, the patient is then asked to stare straight ahead without blinking for as long as possible. The dorsolateral corneal surface is observed with 10X magnification with light passed through the cobalt-blue filter of a slit lamp biomicroscope. TFBUT is measured as the time from eyelid opening to the first sign of tear film breakup, evident as the appearance of 1 or more dark spots within the fluorescent green tear film (14). OPI score is determined by dividing TFBUT by the IBI (13).

An OPI score of less than 1.0 suggests an exposed ocular surface, which may lead to the development or exacerbation of the signs and symptoms of DED; an OPI score of more than 1.0 indicates a tear-protected ocular surface, which potentially results in less severe dry eye signs and symptoms. It can also be used to measure the changes in the severity of DED over time and to evaluate the effect of treatments for DED in promoting tear film stability (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).

OPI 2.0
An “OPI 2.0 System” was developed to evaluate ocular surface protection under a natural blink pattern and normal visual conditions. It is calculated by determining the mean breakup area and dividing it by the IBI. Breakup area can be calculated by automated software algorithms, providing a real-time measurement of corneal exposure for each interblink interval during a one-minute video. The software analyzes a series of artificial images and still image frames captured during an actual clinical session using fluorescein staining videography (16). However, as this method requires advanced software to measure mean break up area, it is difficult to use in routine clinical practice. 

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).

The OPI can be used as a tool to identify patients at risk of developing signs and symptoms associated with dry eye.

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).

Practical considerations
As the OPI is measured using IBI and TFBUT, control should be taken to accurately measure both these parameters (24).

• To determine TFBUT, care must be taken while instilling the fluorescein dye so that reflex tearing is not induced. Changes in tear volume may lengthen TFBUT (25).

• Appropriate patient instructions should be given before the measurement of TFBUT. If patients are not told to blink freely prior to TFBUT being assessed, reflex tearing may result in skewing the subsequent measurements.

• Volume of fluorescein should be accurate for assessment. Large volumes of fluorescein instilled may also artificially lengthen TFBUT (25).

• A slit lamp with an online video camera system may be used to capture TFBUT. Video capture with an on-screen timer allows for precise measurement of the time between the last complete blink and the appearance of the first, growing micelle (25).

• In routine clinical practice, the IBI of the patient can be measured while an ECP is taking history, either during routine conversation or while the patient reads the vision chart. 

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.

Subscribe to The Ophthalmologist Newsletters

When you click “Subscribe” we will email you a link, which you must click to verify the email address above and activate your subscription. If you do not receive this email, please contact us at [email protected].

  1. N Yokoi and G Georgiev, “Tear-film-oriented diagnosis for dry eye,” Jpn J Ophthalmol, 63, 127 (2019). PMID: 30783943.
  2. K Tsubota, “Short tear film breakup time-type dry eye,” Invest Ophthalmol Vis Sci, 59, DES64-DES70 (2018). PMID: 30481808.
  3. N Yokoi and G Georgiev, “Tear-film-oriented diagnosis for dry eye,” Jpn J Ophthalmol, 63, 127 (2019). PMID: 30783943.
  4. J Wolffsohn et al., “TFOS DEWS II Diagnostic Methodology Report,” Ocul Surf, 15, 539 (2017). PMID: 28736342.
  5. M Al-Abdulmunem, “Relation between tear breakup time and spontaneous blink rate,” Int Contact Lens Clin, 26, 117 (1999). PMID: 11166137.
  6. T Inomata et al., “Maximum blink interval is associated with tear film breakup time: A new simple, screening test for dry eye disease,” Sci Rep, 8, 13443 (2018). PMID: 30194447.
  7. Y Su et al., “Spontaneous eye blink patterns in dry eye: Clinical correlations,” Invest Ophthalmol Vis Sci, 59, 5149 (2018). PMID: 30372746.
  8. G Ousler et al., “Factors that influence the inter-blink interval (IBI) as measured by the ocular protection index (OPI),” Invest Ophthalmol Vis Sci, 43, 56 (2002). 
  9. J Craig et al., “TFOS DEWS II Report Executive Summary,” Ocul Surf., 15, 802 (2017). PMID: 28797892.
  10.  K Tsubota, “Short tear film breakup time-type dry eye,” Invest Ophthalmol Vis Sci, 59, DES64 (2018). PMID: 30481808.
  11.  C McMonnies, “The clinical and experimental significance of blinking behavior,” J Optom, 13, 74 (2020). PMID: 31992536.
  12.  Y Su et al., “Spontaneous eye blink patterns in dry eye: Clinical correlations,” Invest Ophthalmol Vis Sci, 59, 5149 (2018). PMID: 30372746.
  13.  G Ousler et al., “The Ocular Protection Index,” Cornea, 27, 509 (2018). PMID: 18520496.
  14.  R Abelson et al., “Measurement of ocular surface protection under natural blink conditions,” Clin Ophthalmol, 5, 1349 (2011). PMID: 22034554.
  15.  G Ousler et al., “The Ocular Protection Index,” Cornea, 27, 509 (2008). PMID: 18520496.
  16.  R Abelson et al., “Validation and verification of the OPI 2.0 System,” Clin Ophthalmol, 6, 613 (2012). PMID: 22570541.
  17.  M Yazdani et al., “Evaluation of the ocular surface disease index questionnaire as a discriminative test for clinical findings in dry eye disease patients,” Curr Eye Res, 44, 941 (2019). PMID: 30955380.
  18.  B Tashbayev et al., “Utility of tear osmolarity measurement in diagnosis of dry eye disease,” Sci Rep, 10, 5542 (2020). PMID: 32218518.
  19.  M Rolando et al., “Protecting the ocular surface and improving the quality of life of dry eye patients: a study of the efficacy of an HP-guar containing ocular lubricant in a population of dry eye patients,” J Ocul Pharmacol Ther, 25, 271 (2009). PMID: 19366323.
  20.  G Ousler et al., “An evaluation of tear film breakup time extension and ocular protection index scores among 3 marketed lubricant eye drops,” Cornea, 26, 949 (2007). PMID: 17721294.
  21.  K Lebow, “An evaluation of two artificial tears in improvement of tear film stability as measured by tear film break-up time and ocular protection index (OPI).” Paper presented at the AAO Annual Conference 2007; 075316. 
  22.  G Torkildsen et al., “Ocular comfort and drying effects of three topical antihistamine/mast cell stabilizers in adults with allergic conjunctivitis: a randomized, double-masked crossover study,” Clin Ther, 30, 1264 (2008). PMID: 18691985.
  23.  M Nebbioso et al., “Fixed topical combinations in glaucomatous patients and ocular discomfort,” Expert Opin Pharmacother, 13, 1829 (2012). PMID: 22770575.
  24.  P Johnston et al., “The interblink interval in normal and dry eye subjects,” Clin Ophthalmol, 7, 253 (2013). PMID: 23403736
  25.  Dry eye: diagnostic test template (2020). Available at: https://bit.ly/2L3ZpP8

About the Authors

Aditi Agarwal

Medical Director and Cornea Consultant at Krishna Netralaya, Gurgaon, and Senior cornea consultant at Fortis hospital, Gurgaon, India.


Rajesh Sinha

Professor of Ophthalmology in Cornea, Cataract and Refractive Surgery at the Dr. Rajendra Prasad Centre for Ophthalmic Sciences, AIIMS, New Delhi, India.

Related Case Studies

The Missing Piece of the Dry Eye Puzzle

| Contributed by Quidel

Uncovering Ocular Comorbidity

| Contributed by Quidel

Finding Ocular Surface Inflammation

| Contributed by Quidel

Product Profiles

Access our product directory to see the latest products and services from our industry partners

Here

Register to The Ophthalmologist

Register to access our FREE online portfolio, request the magazine in print and manage your preferences.

You will benefit from:

  • Unlimited access to ALL articles
  • News, interviews & opinions from leading industry experts
  • Receive print (and PDF) copies of The Ophthalmologist magazine

Register