I have had the privilege to author a number of dry eye/ocular surface disease articles in the past, and I am delighted to say that the core science and management concepts have remained fairly constant over the years. What has changed, however, is the availability of cutting-edge diagnostic and therapeutic technologies designed to meet the challenges of OSD. The modern eye care community is now cognizant of the critical role of the ocular surface/tear film in maintaining clear, comfortable vision and is experienced in the rudimentary OSD testing principles of the past. And finally, our tools for managing OSD are starting to match the sophistication of those found elsewhere in eye care.
In this article, I will review our OSD history and discuss how technology has assisted our ability to manage the disease.
Tear Film
It was in 1903 that German ophthalmologist Otto Schirmer invented his namesake test to quantify tear volume/production.1 That this simple absorbent paper test, developed when Teddy Roosevelt was in the White House, has endured for over a century is testament to its clinical utility. However, in addition to its iatrogenic irritating effect, Schirmer testing has several limitations, including variable results and poor repeatability. These disadvantages remained a limitation of tear testing for eight decades until the phenol red thread test (Zone-Quick, Menicon) was developed by Hikaru Hamano, M.D., in 1982, alleviating—but not completely eliminating—the shortcomings of tear testing.2
Today, we have more modern methods than threads and paper strips. Numerous studies suggest an association between tear meniscus height/curvature/volume and dry eye.3-6
• Optical coherence tomography. We now find practitioners successfully using OCT anterior segment modules as a non-invasive, non-contact modality for imaging/quantifying the tear film and tear meniscus.7 OCT is a quick method for assessing the tear meniscus height, with acceptable sensitivity, specificity and repeatability; thus, it has potential for the diagnosis and evaluation of dry eye disease.7
The OCT anterior segment modules image the tear film and tear meniscus height can then be determined from the scan. Although research labs have designed programs to quantify the volume and/or analyze the data differently, there is currently no commercial software available to do so. As a clinician, I would recommend using the lacrimal lake height measure to objectively evaluate the efficacy of DE management (therapeutics/plugs/other therapy) in conjunction with clinical symptom reports.
• Oculus Keratograph. As an alternative to OCT, the Keratograph corneal topographer (Oculus) can also measure the height of the inferior tear meniscus. In addition, the device can measure tear film break-up time by detecting changes in the instrument-projected placido rings on the cornea and generates a metric that the manufacturer calls the non-invasive keratograph break-up time (NIK-BUT). Oculus suggests that this measure can provide qualitative information on the stability and composition of the tear film by comparing the patient’s findings to a normative database.
Intuitively, there seems to be an advantage to NIK-BUT compared to the “one-Mississippi, two-Mississippi” count in slit lamp/fluorescein aided tear break-up measurements. Released in May 2012, the Keratograph 5M, also from Oculus, can generate meibography images of the upper eyelid as comfortably as the lower eyelid—a unique and useful capability. The accompanying 5M software provides options to mark individual examination fields or select between different representations of the meibomian glands.8
• TearLab Osmolarity System. Aside from assessing tear lipid integrity, tear film osmolarity measurement (now available as an in-office test) has been found to be the single best marker of dry eye disease severity across normal, mild/moderate and severe categories, and has been proposed as a biomarker for dry eye disease severity.9,10
The more highly concentrated tear film (i.e., increased osmolarity) that results when the quantity or quality of secreted tears is compromised places stress on the corneal epithelium and conjunctiva.11 Previously, this measure could only be obtained by laboratory processing of a tear sample. The TearLab Osmolarity System uses just 50nl of tear film—easily recovered from the lacrimal lake near the lateral canthus with a hand-held instrument—to quantify tear osmolarity within three seconds.
Meibomian Gland Dysfunction
• LipiFlow Thermal Pulsation System. Of course, we are also seeing technological advancements in the treatment of MGD. Once relegated to heated, seed-filled socks; warmed, soggy washcloths and shower eyelid massage, MGD therapy has been thoroughly modernized with the LipiFlow Thermal Pulsation System (TearScience). The LipiFlow TPS has been documented to restore meibomian gland function and has been demonstrated to provide relief from symptoms of MGD for as long as 12 months.12
With the LipiFlow, both upper and lower eyelids are treated simultaneously. A disposable shell unit (that vaults the cornea) warms the eyelids to the ideal temperature of 42.5ºC, after which an outer bladder inflates and deflates. This motion gently “massages” the meibomian glands, evacuating stagnant meibum and encouraging more-normal lipid flow. The 12-minute, bilateral procedure is precisely orchestrated by the device.
LipiFlow TPS has a Category III CPT code of 0207T. As the TPS is considered experimental and investigational by most insurance carriers, the treatment is generally not covered and would be considered a private pay procedure.
• Meibomian Gland Evaluator. MGE (Tear Science) is a handheld instrument used to evaluate meibomian gland secretions and is useful in determining which patients may benefit from LipiFlow treatment.
According to the manufacturer, the instrument applies consistent, gentle pressure—between 0.8g/mm2 and 1.2g/mm2—to the outer skin of the lower eyelid.13 The clinician uses a slit lamp to look for lipid expression from the meibomian gland orifices to gauge gland patency and production.
• LipiView Ocular Surface Interferometer. Also from TearScience, this complementary device is used to image the tear film, quantify lipid layer thickness and, importantly, evaluate blink patterns. It does so using broad-spectrum white light interferometry and interferometric color assessment of the tear film by specular reflection.13
• Maskin Meibomian Gland Intraductal Probes and Tubes. Developed by Rhein Medical, these instruments were designed to relieve meibomian gland obstruction and dysfunction. Meibomian gland duct probing is the process of mechanically unblocking obstructions postulated to occur at the orifice and within the lumen of the meibomian gland.14
Meibomian gland probing has been found to improve symptoms and to increase the number of meibomian glands showing expressible meibum.15 Intraductal tubes can be used to instill medications directly into the meibomian glands.
• Maskin Meibum Expressor. The MME (Rhein Medical) assists the evacuation meibomian ducts. After probing has restored patency to the meibomian gland orifice, the clinician places the eyelid between the two rollers on the MME device and gently applies tension to clear the ducts. The instrument’s inventor, ophthalmologist Steve Maskin, found that it works best when moved perpendicularly from the tarsal base toward the lid margin to push squeeze out ductal contents.16
Dr. Maskin’s two instruments, used in concert, are designed to relieve meibomian gland ductal obstruction and evacuate the gland outflow tract.
Blepharitis
Another hand-held instrument used to treat blepharitis, specifically Demodex blepharitis, is the BlephBrush designed by OcuSoft. The BlephBrush is included in the Demodex Convenience kit, a packaged system to help control Demodex overpopulation on the lid margin.
The Demodex mite (Demodex folliculorum and Demodex brevis) is pervasive in human skin and hair. D. folliculorum is found in hair follicles, while D. brevis lives in sebaceous glands. Demodex infestation is associated with recalcitrant symptomatic blepharitis.17-19
The BlephBrush is used to apply a proprietary blend, including tea tree oil, which has acaricidal properties, to the lash line and subsequently remove desquamated skin and debris.20
Inflammation
Hyperosmolar stress on ocular surface epithelial cells stimulates a cascade of inflammatory events by generating inflammatory cytokines.21 Another proposed biomarker for dry eye disease is the level of matrix metalloproteinase-9, an inflammatory marker, in the tears. This can be measured in the office using the RPS InflammaDry Detector kit from Rapid Pathogen Screening.
Once a sample is collected, it takes about 10 minutes for the assay to be assembled and a result read. Positive test results suggest that inflammation of the ocular surface must be addressed via anti-inflammatory or immunomodulatory therapy (e.g., topical steroids or cyclosporine).
Similar in nature to the RPS Adeno Detector, I believe that this point-of-care tool will be the first of many possible diagnostic biomarker tests for DED. InflammaDry is not yet available in the United States, although the company has filed with the FDA. It is currently approved in Canada.
This is an exciting time for clinicians managing dry eye and ocular surface disease. New and developing diagnostic and treatment technologies can be engaged to monitor disease progression or therapeutic success. Patient compliance and satisfaction can be enhanced with tangible markers of positive change.
Remember, a healthy ocular surface and robust tear film sets the stage for successful ocular and intraocular surgeries. These technologies have the potential to provide clinical endpoints to determine success of pipeline therapeutics in dry eye disease, which to date, has been an elusive task in drug development.
Dr. Mastrota is Center Director at the New York Office of Omni Eye Services. Additionally, she serves as secretary of the Ocular Surface Society of Optometry (OSSO).
1. Schirmer O. Studien zur Physiologie und Pathologie der Trþnen absonderung and Trþnen abfŸhr. Grafes Arch Ophthalmol. 1903;56:197-291.
2. Hamano H, Hori M, Mitsunaga S, et al. Tear test (preliminary report). J Jpn CL Soc. 1982; 24:103-7.
3. Shen M, Li J, Wang J, et al. Upper and lower tear menisci in the diagnosis of dry eye. Invest Ophthalmol Vis Sci. 2009 Jun;50(6):2722-6.
4. Chen Q, Zhang X, Cui L, et al. Upper and lower tear menisci in Sjögren’s syndrome dry eye. Invest Ophthalmol Vis Sci. 2011 Dec 9;52(13):9373-8.
5. Cui L, Shen M, Wang J, et al. Age-related changes in tear menisci imaged by optical coherence tomography. Optom Vis Sci. 2011 Oct;88(10):1214-9.
6. Yuan Y, Wang J, Chen Q, et al. Reduced tear meniscus dynamics in dry eye patients with aqueous tear deficiency. Am J Ophthalmol. 2010 Jun;149(6):932-8.
7. Ibrahim OM, Dogru M, Takano Y, et al. Application of visante optical coherence tomography tear meniscus height measurement in the diagnosis of dry eye disease. Ophthalmology. 2010 Oct;117(10):1923-9.
8. Oculus. New Oculus keratograph 5M is released for topography and dry eye screening. Dermwire. 2012 May 8. Available at:
http://bmctoday.net/practicaldermatology/dermwire/view.asp?20120508-new_oculus_keratograph_5m_is_released_for_topography_and_dry_eye_screening. Accessed September 2012.
9. Sullivan BD, Whitmer D, Nichols KK, et al. An objective approach to dry eye disease severity. Invest Ophthalmol Vis Sci. 2010 Dec;51(12):6125-30.
10. Suzuki M, Massingale ML, Ye F, et al. Tear osmolarity as a biomarker for dry eye disease severity. Invest Ophthalmol Vis Sci. 2010 Sep;51(9):4557-61.
11. About dry eye disease. Tearlab. 2012. Available at: www.tearlab.com/products/doctors/aboutded.htm. Accessed September 2012.
12. Greiner JV. Effect of single thermal pulsation treatment on clinical signs and symptoms of meibomian gland dysfunction and dry eye over 12 months. Paper presented at the annual American Society of Cataract and Refractive Surgery meeting, March 25-29, 2011; San Diego.
13. The LipiView Ocular Surface Interferometer. TearScience. Available at:
www.tearscience.com/physician/in-officeprocedure/lipid-science. Assessed July 22, 2012.
14. Maskin SL. Intraductal meibomian gland probing relieves symptoms of obstructive meibomian gland dysfunction. Cornea. 2010 Oct; 29(10):1145-52.
15. Maskin SL. Intraductal meibomian gland probing to restore gland functionality for obstructive meibomian gland dysfunction. Poster presented at the annual American Academy of Ophthalmology meeting, October 23, 2011; Orlando, Fla.
16. Maskin SL. Evacuating the meibomian gland outflow tract. Cataract Refract Surg Today. 2012 Jul;56-8.
17. Gao Y-Y, Di Pascuale MA, Li W, et al. High prevalence of ocular demodex in lashes with cylindrical dandruffs. Invest Ophthalmol Vis Sci. 2005 Sep;46(9):3089-94.
18. Lee SH, Chun YS, Kim JH, et al. The relationship between demodex and ocular surface discomfort. Invest Ophthalmol Vis Sci. 2010 Jun;51(6):2906-11.
19. Liu J, Sheha H, Tseng SC. Pathogenic role of demodex mites in blepharitis. Curr Opin Allergy Clin Immunol. 2010 Oct;10(5):505-10.
20. Gao YY, Xu DL, Huang J, et al. Treatment of ocular itching associated with ocular demodicosis by 5% tea tree oil ointment. Cornea. 2012 Jan;31(1):14-7.
21. Li DQ, ChenZ, Song XJ, et al. Stimulation of matrix metaloproteinases by hyperosmolarity via JNK pathway in human corneal epithelial cells. Invest Ophthalmol Vis Sci. 2004 Dec;45(12):4302-11.
