The Chronic Dry Eye Patient: A Strategy for Achieving and Optimizing Pharmacologic
Success.
Laura A. Vickers, M.D. and Alan N. Carlson, M.D.
History
A 45-year-old caucasian woman presented to the Duke Eye Center for a second
opinion regarding her 2-year history of severe ocular surface dryness involving both eyes,
which was unresponsive to Restasis® (Cyclosporine Ophthalmic Emulsion 0.05%, Allergan,
Inc, Irvine, CA). She complained of severe symptoms, including constant foreign body
sensation, irritation, “tired eyes” and fluctuating vision throughout the day. She was
cosmetically concerned about her persistently red, inflamed eyes. In fact, the patient was so
disturbed by these symptoms and by her appearance that she was functionally limited and
her quality of life was diminished. She had previously responded poorly to frequent usage
of Refresh® artificial tears (Allergan, Inc, Irvine, CA), various oral flax seed and fish oils,
and topical Restasis drops used consistently for one year. She also noted that instillation of
Restasis caused redness and irritation, which added to her frustration. She was previously
employed as a computer analyst and her symptoms worsened after several hours of
computer usage, resulting in significant emotional distress.
Her past ocular history was notable for bilateral upper eyelid blepharoplasty with 3
additional follow-up procedures. Upon questioning, she did endorse worse irritation and
dryness in the mornings. There were no additional positives on an extensive review of
systems, and no relevant past medical or family history.
Examination
The patient’s vision fluctuated with blinking during testing, although after
instillation of artificial tears her best corrected visual acuity was 20/20 in both eyes. On
external examination her eyes were notably red and inflamed. By slit lamp biomicroscopy,
the eyelid margins were thickened and inflamed with telangiectasia and significant
meibomian gland obstruction. The tear meniscus was deficient and the pre-ocular tear film
was notably unstable with a Tear Breakup Time (TBUT) in the right eye of 6 seconds and in
the left eye 3.5 seconds. Basic Schirmer Test (BST) in the right eye was 5 mm and in the left
was 2 mm at 5 minutes. The cornea was otherwise clear without opacity, and the
remainder of the slit lamp and fundus examination were within normal limits. Intraocular
pressures were also normal.
LipiView analysis was performed which identified that essentially 100% of her
blinking was incomplete or partial. LipiView also identified significant fluctuation in the
lipid layer thickness of her tear film between blinks. She was able to forcibly close her eyes
but in a relaxed state, we were able to reproduce lagophthalmos.
Discussion and Diagnosis
Our patient was diagnosed with both aqueous and lipid deficient “evaporative” dry
eye syndrome exacerbated by incomplete blinking. Additionally, given the severity of her
condition and her subjective report of symptoms which were worse upon awakening in the
morning, we suspected nocturnal lagophthalmos resulting from the multiple eyelid
procedures.
The finding of incomplete blinking on LipiView analysis is common among people
who spend hours using the computer as well as those who have undergone previous eyelid
surgery. Our patient underwent the 12-minute LipiFlow thermal pulsation treatment.
Postoperatively she was instructed to continue the use of topical Restasis twice daily and to
keep a diary of her progress. No additional anti-inflammatory medications were used. The
application of Soothe® ophthalmic lubricating ointment (Bausch + Lomb, Rochester, N.Y)
at night was implemented because of the concern for nocturnal lagophthalmos.
On follow-up evaluation 5 weeks after treatment, she reported a remarkable
improvement in ocular redness throughout the day, and was highly satisfied with both
comfort and the cosmetic results. Her morning irritation had resolved with the nightly
application of ophthalmic ointment. The sensation of “tired eyes” and the previously
constant foreign body sensation had almost completely resolved. Restasis no longer caused
ocular discomfort and redness upon instillation.
On slit lamp examination, the lid margins were noticeably less inflamed. The preocular tear film was more stable with TBUT of 9.5 seconds in the right eye and 8 seconds in
the left. The tear meniscus was much more robust and BST measured 15 mm in the right
eye and 5 mm in the left at 5 minutes.
Finally, the patient was optimistic that her improvement in ocular comfort would
allow her to return to the workplace and function more normally throughout the day. The
emotional burden of her symptoms improved greatly leading to a significant improvement
in her quality of life.
“Dry eye” is a very broad term with highly variable clinical presentations.
Frequently, there are inconsistencies between the objective signs of dry eye on
examination and the patient’s subjective experience and perception of the disease. This
can be frustrating for both patient and doctor. This may be due to differences in pain
sensitivity as well as lifestyle, emotional and psychological factors.1 While previously
considered primarily the consequence of deficient tear production, dry eye is now
recognized as a much more complex and prevalent condition where inflammation, poor
tear film quality and instability ultimately result in reduced lubrication and subsequent
repetitive injury to the ocular surface.2 3 An unstable tear film reportedly accelerates tear
evaporation 4-fold, and produces aqueous deficiency as this is the component of the tear
film that readily evaporates.4
The management of this patient’s condition prior to our evaluation demonstrates
what may be the most common error in the management of ocular surface dryness:
treatment guided exclusively by patient symptoms and expectations. Unfortunately, this
approach leads to inconsistency in treatment as it depends on the patient’s subjective
perception of their symptoms. The dry eye patient who goes untreated or inadequately
treated early in their disease course is at risk for progressing to structural changes of the
eyelid margin with gland obstruction, gland atrophy, and ocular surface injury over time
making their condition more resistant to pharmacologic management. This leads to a
common cycle in the doctor-patient relationship wherein the physician encourages
medication compliance while balancing patient expectations for symptomatic
improvement as the disease becomes more difficult to treat. Patients often become
frustrated as they further limit lifestyle activities due to symptoms and continue to take
expensive medications, often unconvinced of their effectiveness.
In such cases, patients may be improperly labeled as Restasis non-responders.
While many patients derive benefit from Restasis, a subset may not initially achieve
symptomatic relief.5 Presumably, this inability to “get ahead” of the inflammatory cascade
in these more challenging patients involves additional inflammatory and structural factors
that remain inadequately treated. We observe that the most consistent finding among
patients labeled as nonresponsive or poorly responsive to Restasis is the insufficient
treatment of meibomian gland and eyelid margin disease. While Restasis has a role in
treating the inflammation resulting from a sequel of meibomian gland dysfunction, less
responsive patients may require a more aggressive incorporation of adjuvant therapies to
maximize their beneficial response to Restasis.4
Our patient underwent LipiView analysis revealing inadequate blink quality along
with a deficient and unstable lipid layer in the tear film.6 LipiFlow Thermal Pulsation
Therapy was then employed to address her meibomian gland obstruction, reduce eyelid
inflammation and improve the tear film quality by enabling a more normal meibomian
gland secretion.7 The use of ointment addressed the previously untreated nighttime
lagophthalmos. Restasis became more comfortable to use and appears to now be more
effective by synergistically improving tear film stability by reducing ocular surface
inflammation. 8 This case illustrates that some patients may be labeled as a non-responder
to pharmacologic treatments such as Restasis, while the inciting mechanism was an
inadequate tear film from increased evaporation resulting from obstruction and
hyposecretion of the meibomian glands.
In our practice, we have observed late intervention and inadequate treatment of
associated eyelid conditions to be the most prevalent cause of pharmacologic failure in dry
eye syndrome, even more so than medication noncompliance. We therefore make the case
that a more proactive and comprehensive approach to evaluation and treatment of the dry
eye patient is warranted to achieve the subjective and objective pharmacologic benefits of
Restasis, especially in patients labeled as Restasis non-responders.
Conclusion
Our patient’s dry eye condition was initially managed inadequately with respect to
her meibomian gland dysfunction and lagophthalmos. LipiFlow Thermal Pulsation
Therapy and the application of ophthalmic lubricating ointment at night addressed these
problems. Initially labeled as a Restasis non-responder after one year of treatment, our
patient is now experiencing a very favorable subjective benefit from Restasis. Dry eye is a
complex disease state with significant physical and psychological consequences, and
patients should thus undergo a comprehensive evaluation and treatment strategy. Restasis
non-responders have the potential to respond more successfully after concomitant ocular
surface problems are appropriately addressed through synergistic modalities.
References
1.
Vehof J, Kozareva D, Hysi PG, et al. Relationship between dry eye symptoms and pain
sensitivity. JAMA ophthalmology 2013;131:1304-8.
2.
Shimazaki-Den S, Dogru M, Higa K, Shimazaki J. Symptoms, visual function, and
mucin expression of eyes with tear film instability. Cornea 2013;32:1211-8.
3.
The definition and classification of dry eye disease: report of the Definition and
Classification Subcommittee of the International Dry Eye WorkShop (2007). The ocular
surface 2007;5:75-92.
4.
Prabhasawat P, Tesavibul N, Mahawong W. A randomized double-masked study of
0.05% cyclosporine ophthalmic emulsion in the treatment of meibomian gland dysfunction.
Cornea 2012;31:1386-93.