Diagnosing and treating dry eye with technology

It is estimated that over 25 million people suffer from dry eye to one degree or another in the United States. Some $3.8 billion annually is spent on various forms of dry eye relief in the U.S. alone.¹

All of us in clinical practice realize that dry eye is the most frequently encountered eye disease state that we see. Our understanding of dry eye and ocular surface disease is expanding at exponential rates. This is allowing us to more accurately diagnose specific forms of dry eye and determine their root causes.

From these specific diagnostic states, we can then tailor targeted therapies to more effectively manage our patients. In this article, I will review some of the latest developments in advanced technologies available for both the diagnosis and treatment of dry eye and ocular surface disease.

Diagnostic technologies

Tear film analysis and ocular surface diagnostic software

The Keratograph 5M by Oculus is primarily designed as an advanced Placido-based topography system; however, additional illumination, imaging, and software systems dramatically expand the diagnostic applications of the instrument.

Diagnostics geared toward dry eye and ocular surface make this instrument a multifunctional powerhouse. The following are some of the key software programs available for the K5 system.

Related: A new tool for managing ocular surface disease

Tear film stability. Tear film stability has traditionally been evaluated by performance of invasive tear film break-up time measurements by observing dry spot formation on the cornea following instillation of sodium fluorescein. K5 has software that non-invasively quantifies tear film break-up time on multiple areas throughout the corneal surface.

The video imaging system detects distortions of the Placido rings reflected on the ocular surface as the tear film breaks up and evaporates. The system can indicate break-up of the tear film down to 0.1-second increments.

Normative data for first break-up time and average break-up time has been determined and can be used to categorize tear film stability. In addition, observation of the corneal area of break-up and the slope of the break-up time graph gives the clinician a clear indication of the stability of the pre-corneal tear film.

Tear volume. Tear volume can be evaluated by measurement of the height of the inferior tear meniscus

. Typically a qualitative evaluation of the height is done by slit-lamp observation of the inferior tear meniscus. K5 software can image the inferior tear meniscus and allow for quantitative measurement via the use of computer-generated calipers.

Accuracy of measurements can be made down to 0.1-mm increments. Population studies have shown that normal inferior tear meniscus is typically above 0.20 mm.² Typically, images are captured with infrared illumination to avoid reflex tearing from bright visible light illumination.

Observation of particulate matter in the tear film in terms of speed of movement with the blink correlates with tear film thickness. Slower movement of the tear film with blink is associated with a thicker tear film. K5 can video capture illumination of particulate matter in the tear film, and the examiner can observe and assess tear film movement. Future development will allow for quantification of this function.

A thicker and more stable superficial lipid layer of the tear film is critically important in maintaining tear film stability. Illumination of the tear film with K5 by imaging white Placido rings, capturing the image, and observing the degree of coloration of the bifringence pattern will give a qualitative assessment of the thickness of the lipid layer.

Future software development will allow for quantification of the lipid layer thickness.

Related: Diagnosing and treating lagophthalmos

The health of the meibomian glands is currently thought to be one of the most critical elements in assessing the status of the ocular surface. Meibomian gland disease (MGD) is associated with reduced production of lipid for the tear film and is considered the primary cause of dry eye disease.³

K5 has imaging capability to capture infrared images of the meibomian glands of the upper and lower lid (meibography). Enhancement software makes the detection of glands more obvious. Observation of these images can detect dropout of meibomian glands associated with MGD. Various systems of grading dropout are being developed.

Reimbursement. Billing for K5 dry eye software can be approached in a number of ways. Some practitioners include these tests as part of a dry eye diagnostic workup.

Some bill medical insurance for that workup utilizing evaluation and management (E&M) codes (99XXX codes), while others think these tests are not part of such an office visit and should be charged separately. Most practitioners I have spoken with will then charge a fee directly to the patient after presenting an advanced beneficiary notification of non-coverage form (ABN). S

ome practitioners have billed medical insurance for some of the imaging procedures utilizing CPT code 92285 (external ocular imaging with interpretation and report).

Next: Lipid layer thickness, meibography, and blink patterns 

Lipid layer thickness, meibography, and blink patterns evaluation

TearScience’s LipiView II system is a highly accurate instrument initially developed to precisely measure tear lipid layer thickness. It also enables practitioners to evaluate blink characteristics such as blink rate and the presence of incomplete blink.

The most recent version of the system has added a high-resolution infrared meibography component. Although most often used in combination with the therapeutic LipiFlow system, LipiView is now available as a standalone diagnostic instrument.

The system utilizes interferometry to measure lipid layer thickness down to the submicron level of accuracy. It further incorporates what the manufacturer terms dynamic meibomian imaging (DMI) to produce detailed images of the meibomian glands in order to demonstrate ductal gland dilation plus gland atrophy and dropout, which are common to MGD.

Related: Screen younger patients for dry eye

The Meibomian Gland Evaluator (MGE), also produced by Tear Science, allows the eyecare practitioner to evaluate meibomian gland secretions. The instrument provides a standardized method to apply consistent, gentle pressure between 0.8 g/mm2 and 1.2 g/mm2 to the outer skin of the lower eyelid which approximates the force of a normal blink.

The presence of liquid from a meibomian gland orifice (visualized through a slit-lamp biomicroscope) during expression indicates the meibomian gland is not obstructed.

Alternative quality of expression or lack of expression suggests MGD. Expression grading is recorded as 0 = no secretions; 1 = ispissated (toothpaste-like) secretions; 2 = colored or cloudy liquid secretions; 3 = clear oil secretions.

Reimbursement. Practitioners typically bill for LipiView II as an out-of-pocket fee directly to the patient with the presentation of an ABN form. Again, some perform the procedure as part of a dry eye diagnostic workup and bill medical insurance using E&M codes.

Performance of testing with the MGE typically follows similar billing patterns. TearScience suggests that the DMI element of LipiView II can be billed to insurance carriers utilizing the 92285 code (external ocular imaging with interpretation and report).

Next: Tear film osmolarity measurement

Tear film osmolarity measurement

Elevation of tear osmolarity is an integral part of the definition of dry eye disease, according to the DEWS study group report.⁴ Many commonly performed clinical tests for dry eye diagnosis suffer from poor specificity and sensitivity for disease detection. Osmolarity has very high predictive value (87 percent) for the detection of dry eye disease.^4,5

Related: Using the SPEED questionnaire to identify dry eye

TearLab Osmolarity is an in-office system used to measure tear film osmolarity. Following a quick sampling of 50 nanoliters of tear from each eye, the system will report osmolarity in milliosmoles per liter (mOsm/L). Evaluation of the maximum reading between the two eyes and the asymmetry of readings between the two eyes is used in the diagnosis of dry eye.

According to TearLab, values above 308 mOsm/L for the higher of the two eyes as well as an asymmetry of readings of 10 mOsm/L or more between the two eyes indicates the presence of dry eye disease.

Although osmolarity does not specifically indicate the type of dry eye or cause of dry eye, it can be used to not only initially assess for the presence of dry eye (vs. other potential causes of patient symptomatology), but can be used to monitor the efficacy of implemented therapies by comparing pretreatment vs. post treatment values.

Reimbursement. Billing for TearLab osmolarity testing has been CLIA waived, has an approved CPT code of 83861, and is billed per eye.

Next: MMP-9 detection

MMP-9 detection

Rapid Pathogen Screening (RPS) InflammaDry is an immunoassay test designed to detect elevated levels of matrix mettaloproteinase (MMP-9) in the tears. MMP-9 is an inflammatory marker that is known to be elevated in patients with dry eye disease. MMP-9 is a cytokine produced by epithelial cells experiencing inflammation. It is the only test of this kind on the market, and the company claims high sensitivity and specificity.

The test is easy to administer, and no anesthetic is required. A patient’s tear sample is taken from the inferior palpebral conjunctiva. Once the tears are collected, the applicator is dipped into a solution for 15 to 20 seconds. This solution is able to detect MMP-9 within the tears.

A red line appears on the applicator if the tears are positive for MMP-9 (> 40 ng/ml). The intensity of the red line will increase as the levels of MMP-9 are higher. A blue line will appear for negative results, and no lines will appear if the test is invalid.

The test can be administered in-office and takes about 10 minutes from start to finish for results. Positive results allow the practitioner to begin anti-inflammatory therapy to improve the patient’s eye comfort and health while reducing dry eye symptoms. Again follow up testing can be used to confirm control of inflammation with therapy.

Reimbursement. Billing for InflammaDry has also been CLIA-waived and has an approved CPT code of 83516, which is billed per eye.

Next: Microassay measurement

Microassay measurement

TearScan Microassay system from Advanced Tear Diagnostics enables the practitioner to obtain measures of tear levels of lactoferrin and IgE. Lactoferrin levels are thought to be an indicator of lacrimal gland function.⁶ Low levels of lactoferrin would suggest an aqueous deficient form of dry eye; however, it should be noted that both aqueous deficient dry eye and evaporative dry eye may co-exist.³ IgE levels are indicators of allergic inflammation.⁷

Commonly, practitioners are confounded about the primary cause of patient symptoms. Both dry eye and allergic ocular surface problems can result in similar subjective symptoms and even confusing physical clinical findings. Use of this technology can assist in the clinical evaluation and potential differential diagnosis. A tiny 0.5-microliter sample of tear is collected for each test, and the system will analyze the sample to provide quantified outcomes in seconds. 

Related: Creating a dry eye protocol

Reimbursement. According to the company,⁸ billing for TearScan utilizes CPT codes 83520 for lactoferrin testing (Definition: Immunoassay for analyses other than infectious agent antibody or infectious agent antigen; quantitative) and 82785 for ocular IgE testing (Definition: Gammaglobulin E (IgE), Total).

For testing the second eye, the AMA recommends:  “using the “-59” modifier for the second eye tested to indicate a “Distinct Procedural Service.” Individual payers may require using Lt or Rt modifiers. Check with your payer for specific instructions.”

Next: Therapeutic technologies

Therapeutic technologies

TearScience LipiFlow

TearScience’s LipiFlow system uses a patented technology to apply heat and pressure to the inner eyelid, optimizing its ability to heat and reduce obstruction of the meibomian glands in a safe and comfortable manner.

According to the company, the activator vaults the cornea and heats to a maximum of 43 degrees C (109 degrees F), reaching inner eyelid glands while protecting cornea, eyelid, and globe. A feedback loop sends pulsed sequences to expel gland blockages with energy focused only on the eyelid.

According to FDA regulations, LipiFlow Activator is a one-time use disposable unit. Treatment with LipiFlow takes approximately 12 minutes per eye, and the reported duration of therapeutic effect can last for over 9 months in many cases.⁹

Reimbursement. Billing for LipiFlow is typically as an out-of-pocket treatment procedure (with suggested use of an ABN form). There is no approved code for LipiView treatment.

MiBo Medical Systems MiboFlow Thermoflow

The MiboFlow Thermoflow (MiBo Medical Systems) is a newly introduced device that provides a consistent temperature of 108 degrees F (± 3 percent) to the external eyelid surface with a thermoelectric heat pump. The goal of treatment is to liquefy the obstructed contents of the meibomian glands.

The dual eye pad transfers heat via applied ultrasound gel to the external surface of the eyelids, directing heat uniformly to the meibomian glands. Treatments typically last 10 to 15 minutes, three sessions performed at two-week intervals are suggested for optimal outcomes. According to the company, duration of treatment effect may last from six to 12 months.

Reimbursement. Billing for MiboFlow is similar to LipiFlow in that there is no approved CPT code for this procedure, and direct-to-patient billing is typical, along with the use of an ABN form. Some practitioners charge per treatment, while others charge a single fee for a suggested series of three treatments.

Next: Rysurg BlephEx

Rysurg BlephEx

The BlephEx instrument (Rysurg) was initially introduced as a treatment for debris accumulation on the eyelids associated with anterior blepharitis; however, practitioners have found it to be effective in the management of MGD as well due to its ability to desquamate the lid margin and remove biofilms that accumulate in this area.

The patented BlephEx hand piece is used to spin a medical-grade micro-sponge along the edge of the eyelids and lashes, removing scurf and debris and exfoliating the eyelid margin. The micro-sponge is lubricated with solution used for lid hygiene and a fresh micro-sponge is used for each lid (total of four for a bilateral treatment).

The lids are rinsed well following the procedure, and home-based eyelid maintenance care is prescribed. According to Rysurg, the duration of therapeutic effect can range from four to six months.

Reimbursement. Billing for BlephEx is usually direct to patient with the use of an ABN form because it also does not have an approved CPT code. Some practitioners combine treatment procedures such as BlephEx and MiboFlow or LipiView or others and charge one fee for the grouped treatments.

Next: Intense pulsed light therapy

Intense pulsed light (IPL) therapy for treatment of MGD

Initially used as a treatment for dermatological conditions such as facial rosacea, Rolando Toyos, MD, first described the use of IPL for the treatment of MGD and began treating patients in this way in 2002.¹⁰ IPL provides powerful bursts of light at specific wavelengths from a xenon flash lamp (in this case, between 500 and 800 nm) to cause changes in blood vessels near the surface of the skin, raise skin temperature, and eliminate pathological bacteria on the skin and eyelids, all of which may have a beneficial effect on MGD.

The proposed mechanism of action for MGD includes increased temperature to liquefy the meibomian gland secretions, reduction of release of inflammatory mediators via occlusion of the superficial vessels, and direct anti-microbial action against both bacteria and demodex. Treatment is performed from ear to ear over the facial area below the eyelids.

The upper lids are not directly treated, and the eyes are shielded during treatment. Expression of the meibomian glands is suggested immediately following treatment. A steroid and NSAID drop is often prescribed for a few days as well. Three to four monthly treatments are suggested in order to obtain a maximum therapeutic outcome. Duration of effect is may range from six to 12 months following an initial treatment regimen.¹¹

Reimbursement. Billing for IPL treatments follow the same lines as indicated for MiboFlow previously in that patients are billed directly with an ABN form and can be billed per procedure or bundled for a series of treatments.

Related: Assess dry eye from a systemic standpoint

Summary

Ocular surface and dry eye diseases are some of the most common pathologies faced by eyecare practitioners on a daily basis. New and more advanced technologies allow us to better differentially diagnose and treat our patients than ever before.

However, it should be clearly stated that we cannot forget the importance of basic diagnostic methods (such as a dry eye-oriented history, detailed slit-lamp evaluation that includes careful observation of the lids and meibomian glands, vital staining, and tear film observation) and basic treatment techniques (such as use of appropriate ocular surface lubricants, attention to proper nutrition and nutritional supplements, and topical and/or oral anti-inflammatory prescriptive therapies among others) that can be performed by all eyecare practitioners.

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References:

1. Comprehensive Report on the Global Dry Eye Products Market. Marketscope. 2013.

2. W Sickenberger et al. Comparison and repeatability of two different methods for tear meniscus height measurement. Poster presented at American Academy of Optometry 55th Annual Meeting; 2010 Dec 7-10; Denver.

3. Asbell PA, Stapleton FJ, Wickström K, Akpek EK, Aragona P, Dana R, Lemp MA, Nichols KK. The international workshop on meibomian gland dysfunction: report of the clinical trials subcommittee. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):2065-85.

4. International Dry Eye Workshop. The definition and classification of dry eye disease. In: 2007 Report of the International Dry Eye Workshop (DEWS). Ocul Surf. 2007; 5 (2): 65-204.

5. Tomlinson A, Khanal S, Ramaesh K, Diaper C, McFadyen A. Tear film osmolarity: determination of a referent for dry eye diagnosis. Invest Ophthalmol Vis Sci. 2006 Oct;47(10):4309-15.

6. Danjo Y, Lee M, Horimoto K, et al. Ocular surface damage and tear lactoferrin in dry eye syndrome. Acta Ophthalmol (Copenh.) 1994;72(4):433-437

7. Friedlaender MH. Ocular allergy. Curr Opin Asthma Clin Immunol 2011;11:477-482.

8. Advanced Tear Diagnostics Reimbursement. http://teardiagnostics.com/resources/technical-manuals/cpt-codes/. Accessed 4/16/15.

9. Greiner JV. A single LipiFlow Thermal Pulsation System treatment improves meibomian gland function and reduces dry eye symptoms for 9 months. Curr Eye Res. 2012 Apr;37(4):272-8

10. Toyos R, McGill W, Briscoe D. Intense pulsed light treatment for dry eye disease due to meibomian gland dysfunction; a 3-year retrospective study.  Photomed Laser Surg. 2015 Jan;33(1):41-6.

111. Kent C. Intense Pulsed Light: For Treating Dry Eye. Rev Ophthalmol. 2010. Available at: http://www.reviewofophthalmology.com/content/d/technology_update/i/1353/c/25857/. Accessed 4/16/15.