Blog: A different approach to treating dry eyes in Japan

May 17, 2019

The views expressed here belong to the author. They do not necessarily represent the views of

The views expressed here belong to the author. They do not necessarily represent the views of Optometry Times or MultiMedia Healthcare.

In the U.S., the key factor in the pathogenesis of dry eye is considered to be inflammation. Artificial tears may temporarily alleviate the symptoms of dry eye, but they don’t target inflammation.

Recommending artificial tears for a disease that is chronic and progressive is like throwing water to put out the smoke but not the fire.

To put out the fire, prescription medications such as topical cyclosporine 0.05% (Restasis, Allergan) or lifitegrast 5% (Xiidra, Shire) are used because they are specifically designed to target inflammation in dry eye patients.

Previously by Dr. Recalde: Blog: 10 eyecare apps for more efficient patient care

By contrast, the Asia Dry Eye Society (ADES) offers a fresh perspective on the etiology of dry eye. Founded in 2012, this society consists of approxmiately 100 physicians from countries across Asia.

These dry eye experts believe the etiology of dry eye is mainly caused by tear instability.1 While inflammation as a key factor is acknowledged, ADES believes it occurs as a result of dry eye rather than being the root cause.

Hence, medications that target inflammation-such as topical cyclosporine and lifitegrast-are not even approved for dry eye treatment in Japan .

Let’s further explore Japan’s perspective on treating dry eye.

Related: Blog: Modern-day techniques for diagnosing dry eye disease


Definition of dry eye

ADES released its consensus report in January 2017.

The organization defines dry eye as “a multifactorial disease characterized by unstable tear film causing a variety of symptoms and/or visual impairment, potentially accompanied by ocular surface damage.”1

In July 2017, the Tear Film and Ocular Surface Society (TFOS) released the second Dry Eye Workshop (DEWS) report (TFOS DEWS II).

TFOS DEWS II defines dry eyeas “a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.”

Both definitions agree that dry eye is a multifactorial disease and that tear film instability plays a role.

However, ADES’s core definition of dry eye is an unstable tear film, whereas TFOS DEWS II’s central theme is loss of homeostasis. It is interesting that loss of homeostasis, hyperosmolarity, ocular surface inflammation, and neurosensory abnormalities were omitted in the ADES definition.1,2

ADES debated whether to include inflammation in its definition but ultimately decided it was not pivotal in the core mechanism of dry eyes.

Related: How to address the three aspects of dry eye disease

Diagnosis of dry eye
The ADES definition of dry eye was specifically tailored to make it practical for diagnosis. To detect an unstable tear film, the measurement of tear film break-up time (TFBUT) is required.

The test is administered with a fluorescein strip, and the patient is asked to blink three times, then asked to hold her eyes open until the doctor notices the first dark spot on the cornea while using a stopwatch to time the interval.

The average of three measurements is used for the final TFBUT. TFBUT >5 seconds is considered normal, while TFBUT <5 seconds is considered abnormal and indicative of dry eye.

After TFBUT is completed, ocular surface damage with fluorescein dye is evaluated.

To measure symptoms of dry eyes or visual impairment, validated questionnaires are used. The ADES committee recommends using the following:

• Dry eye-related quality of life (QOL) score
• Ocular Surface Disease Index (OSDI)
• McMonnies questionnaire
• Women’s Health Study questionnaire

In addition, a questionnaire with visual impairment related to dry eye could supplement these questionnaires to aid in the diagnosis of symptoms related to dry eye.

Related: Dry eye protocol for any practice

Tear film dynamics
A novel way of diagnosing dry eye is analyzing tear film dynamics using the fluorescein break-up pattern of the tear film. 

ADES created a classification system for six distinct patterns of fluorescein break-up patterns:

• Area break
• Line break
• Spot break
• Dimple break
• Random break
• Line or random break with rapid expansion

By combining these patterns with epithelial damage, the pathophysiology can be classified into three dry eye subtypes:

• Aqueous deficient dry eye (ADDE)
• Decreased corneal wettability dry eye (DWDE)
• Increased evaporation dry eye (IEDI)

Target therapy is then prescribed to replenish the abnormal layer of the tear film. ADDE requires aqueous fluid supplementation using artificial tears, sodium hyaluronate (Hymoist, Proxima [FDC Limited]), 3% diquafosol sodium (Diquas, Santen Pharmaceutical Co Ltd), or punctal plugs. 

Related: Why osmolarity should the top test for tear film evaluation 

Alternatively, DWDE necessitates more mucin and is replenished with diquafosol sodium or rebamipide (Mucosta ophthalmic suspension 2%, Otsuka Pharmaceutical Co Ltd). 

Lastly, lipid and/or mucin deficiency with IEDI is treated with warm compresses, lid hygiene, low-dose ophthalmic ointment or diquafosol sodium. LipiFlow (Johnson & Johnson Vision) is not approved for the treatment of meibomian gland dysfunction (MGD) in Japan.

On an additional note, inflammation treatment was discussed briefly and is treated with steroids, rebamipide, and cyclosporin for those countries that have approval.

It is remarkable to learn how eyecare providers in Japan diagnose and treat dry eyes compared to the U.S. The innovative, methodical approach of analyzing tear film dynamics provides customized targeted therapy to each layer of the tear film.

Perhaps with future studies we will have a better understanding of how both tear film instability and inflammation contribute to the pathogenesis of dry eyes.

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References:

1. Tsubota K, Yokoi N, Shimazaki J, Watanabe H, Dogru M, Yamada M, Kinoshita S, Kim HM, Tchah HW, Hyon JY, Yoon KC, Seo KY, Sun X, Chen W, Liang L, Li M, Liu Z, Asia Dry Eye Society. New perspectives on dry eye definition and diagnosis: a consensus report by the Asia Dry Eye Society. Ocul Surf. 2017 Jan;15(1):65–76.
2. Craig JP, Nichols KK, Akpek EK, Caffery B, Dua HS, Joo CK, Liu Z, Nelson JD, Nichols JJ, Tsubota K, Stapleton F. TFOS DEWS II Definition and Classification Report. Ocul Surf. 2017 Jul;15(3):276-283.
3. Yokoi N, Georgiev GA. Tear film–oriented diagnosis and tear film–oriented therapy for dry eye based on tear film dynamics. Invest Ophthalmol Vis Sci. 2018 Nov 1;59(14):DES13-DES22.