Download A Treatment Option for Moderate-to

CORNEA/EXTERNAL DISEASE
A Treatment Option for
Moderate-to-Severe
Dry Eye Syndrome
Implanting a hydroxypropyl cellulose insert.
BY JODI LUCHS, MD
D
ry eye syndrome is a chronic, progressive disease that may permanently damage the ocular
surface if not adequately treated. Its symptoms
adversely affect visual function, the performance of the activities of daily living, and quality of life.1
The Beaver Dam Eye Study demonstrated that the incidence of dry eye increases with age, from more than 10%
among those aged 48 to 59 years to nearly 18% in those
aged 80 years or older.2 The use of a of a self-administered
hydroxypropyl cellulose insert is an effective treatment
option for patients suffering from moderate-to-severe
dry eye syndrome.
ADVANCES IN TREATMENT
Dry eye patients seek relief of the symptoms that
hamper their lives and, in some cases, severely limit
activities such as reading, operating a computer, working, driving, and watching television.3 The Report of the
Management and Therapy Subcommittee of the
International Dry Eye Work Shop (DEWS) noted that,
although dry eye symptoms can rarely be eliminated,
they can be improved, thus enhancing the individual’s
quality of life.4
Dry eye is a multifactorial condition, the contributing
causes of which can include aging, hormonal changes
during menopause, a dry environment, sun exposure,
common systemic medications, LASIK, ocular injury, and
other problems with the eye or eyelids. For that reason, a
combination of treatments is frequently prescribed.5 In
recent years, dry eye treatment has received greater attention from eye care practitioners, as their knowledge base
and treatment options have increased considerably. In
addition to artificial tears and ointments, treatments may
include anti-inflammatory agents and punctal plugs or
other surgeries.
Figure 1. The Lacrisert hydroxypropyl cellulose insert.
LIMITATIONS ON TREATMENT OF
MODERATE-TO-SEVERE DRY EYE
There is, however, a subset of patients already on multifaceted treatment regimens who have persistent symptoms
and require additional relief. These patients tend to have
moderate-to-severe dry eye. In a 2008 survey of ophthalmologists, 94% of respondents agreed that more treatment
options are needed for moderate-to-severe dry eye. Only
33% overall felt that current therapies were extremely or
very effective for moderate cases and only 5% for severe
disease.6
One issue in the management of moderate-to-severe
dry eye has been the lack of correlation between patients’
symptoms and the results of clinical tests. This discrepancy may be due to the variability of the disease process, the
subjective nature of symptoms, and the variability of
responses to questions about physical sensations in the
eyes.1 However, in general, patients with moderate-tosevere disease are typically those with DEWS severity levels 2 through 4.7
The foremost objectives in caring for patients with dry
eye disease are to improve their ocular comfort and return
the ocular surface and tear film to a normal, homeostatic
SEPTEMBER 2010 ADVANCED OCULAR CARE 37
CORNEA/EXTERNAL DISEASE
Figure 2. Demonstration of the insertion of the Lacrisert.
state.4 In their quest for ocular comfort and relief of symptoms, patients with moderate-to-severe dry eye often report
that they need to frequently use lubricants such as artificial
tears, which can be inconvenient.1
The use of punctal plugs is another step in treating
moderate-to-severe dry eye, especially when the condition
is unresponsive to artificial tear drops and ointments.
Punctal plugs can increase comfort and reduce the frequency with which some dry eye patients use artificial tears .
HYDROXYPROPYL CELLULOSE INSERT
An alternative to the frequent use of artificial tears is
Lacrisert (Aton Pharma, Inc.). This hydroxypropyl cellulose
prescription insert helps to retain moisture, stabilize the tear
film, and lubricate the eye (Figure 1).
The insert is approved by the FDA for use in patients with
moderate-to-severe dry eye syndrome. It contains 5 mg of
hydroxypropyl cellulose. The patient places the insert into
the inferior cul-de-sac of his or her eye (Figure 2), where the
medication slowly dissolves over the course of a day and
acts to thicken the precorneal tear film. A plastic applicator
supplied with the product helps the patient to administer
the medication.
Lacrisert was approved by the FDA and introduced more
than 20 years ago. Because dry eye awareness was lower and
practitioners were less aggressive about treating it, however,
the medication was not widely used and was in scarce supply until 2006, when Aton Pharma Inc. acquired the rights
to distribute it. It is one of only two prescription medications specifically indicated for use in dry eye treatment. Past
clinical studies have demonstrated the insert’s ability to
improve dry eye symptoms, to increase tear film breakup
time, and to decrease rose bengal staining.8-13
HYDROXYPROPYL CELLULOSE INSERT
REGISTRY STUDY RESULTS
A recent large, multicenter patient registry study found
that Lacrisert significantly decreased ocular surface disease
index (OSDI) scores in patients with moderate-to-severe dry
eye after 1 month of treatment.14
A patient registry study is designed to examine a wide
range of correlations and show predictive relationships in a
38 ADVANCED OCULAR CARE SEPTEMBER 2010
Figure 3. Change in mean OSDI scores by dry eye severity
group.
Figure 4. Change in distribution of patients within dry eye
severity groups.
“real-world” situation. In a registry, clinicians may choose to
continue or discontinue the patient’s previous treatment
regimen. This allows the collection of data that reflect treatments employed in actual clinical practice, a key consideration for a condition requiring multifaceted treatment like
dry eye.
The multicenter study enrolled 520 patients, aged 18 or
older, with a diagnosis of bilateral dry eye syndrome and a
history of using artificial tears. At their first visit, patients
were given a general dry eye evaluation, screened by slitlamp biomicroscopy and BCVA, and were required to fill
out a questionnaire that included the OSDI, a validated
measure of quality of life. The patients enrolled in the study
were then categorized according to their OSDI scores as
severe, moderate, mild, or normal.
Patients were trained on the proper insertion and use of
Lacrisert. They were contacted by telephone on day 3 of the
study for follow-up and reinstruction. At the second visit
(week 4), patients were given a clinical evaluation and
required to complete a second evaluation. Answers provided on questionnaires (scored on Likert-type scales) were
used to determine changes in patient-reported outcomes
such as symptoms and quality of life.
In patients who completed the study (n = 418), analysis of
variance showed significant differences in OSDI scores
between severity groups after 4 weeks of treatment with
CORNEA/EXTERNAL DISEASE
Lacrisert (Figure 3). The largest decrease
CLINICAL APPLICATION
in scores was 29.8% in the severe group
The author prescribes Lacrisert for
(P < .001). Scores in the moderate group
symptomatic relief to patients who show
decreased by 18.9% (P = .016).
signs of moderate-to-severe dry eye,
Improvements in OSDI scores for
especially those who use artificial tears
patients in the study were over and
frequently (six or more times daily).
above any improvement patients might
Lacrisert is a lubricant, so relief is immehave gained from dry eye therapies
diate. Because the insert has no interacadministered before the study. Blurred
tions with other ocular medications, it is
vision was the most common adverse
not contraindicated in patients who use
effect, reported by 8.7% of study particiother dry eye products, including
pants overall.
cyclospoprine. Lacrisert can be comIt should be noted that, within the
bined with other medications, such as
Figure 5. Change in frequency of
normal and mild OSDI groups, there
anti-inflammatory drugs, if greater treatdifficulty in performing activities of
were significant increases in OSDI scores
ment is required.
daily living within the severe group.
of 83.7% (P = .001) and 30.2% (P = .01),
If patients are experiencing some blurrespectively. In these cases, thickening an
ring in the hours following insertion, the
adequate precorneal tear film may result
author recommends Lacrisert be insertin some blurring of vision. In mild cases of
ed in the evening. Insertion at night
dry eye, any increase in blur may be perallows them to overcome this transient
ceived by the patient as “poor vision.”
issue while they are sleeping and still
Blurriness and poor vision both are comexperience the benefits of the sustained
ponents of the OSDI.
release of tears throughout the day. ■
A shift in the distribution of patients
Dr. Luchs is an assistant clinfrom severe to less severe was also noted
ical professor of ophthalmology
(Figure 4). At baseline, 78% of patients
and visual sciences at the
who completed the study were classified
Albert Einstein College of
as moderate to severe using the OSDI.
Figure 6. Increase in tear film
Medicine in Bronx, New York,
After 4 weeks of therapy, only 59% were
breakup time within the severe
codirector of the Department of Refractive
categorized as moderate to severe. The
group.
Surgery at the North Shore/Long Island
normal and mild populations almost
Jewish Health System in New York, and
doubled in size.
director of clinical research and cornea/external disease at
In the group classified as severe OSDI, 65.3% of patients
South Shore Eye Care in Wantagh, New York. He has received
initially scored within the severe range. After 4 weeks of
honoraria from Aton Pharma, Inc., for consulting services.
therapy, only 44% of the group scored within the severe
Dr. Luchs may be reached at (516) 785-3900; [email protected].
range, shifting the distribution to normal, mild, and moderate groups. Within the severe group, the frequency of diffi1. The epidemiology of dry eye disease:report of the epidemiology subcommittee of the international dry eye workshop
culty performing the activities of daily living decreased
(2007). Ocul Surf.2007;5(2):93-107.
2. Moss SE,Klein R,Klein BE.Incidence of dry eye in an older population.Arch Ophthalmol.2004;122(3):369-373.
(Figure 5); there was a significant improvement in reading,
3. Miljanovic B,Dana R,Sullivan DA,Schaumberg DA.Impact of dry eye syndrome on vision-related quality of life.Am J of
Ophthalmol.2007;143(3):409-415.
watching television or movies, shopping, and performing
4. Management and therapy of dry eye disease:report of the management and therapy subcommittee of the international
housework (P < .001 for all). In the severe group, there was
dry eye workshop (2007).Ocul Surf.2007;5(2):163-178.
5.Yu EY,Leung A,Rao S,Lam DSC.Effect of laser in situ keratomileusis on tear stability.Ophthalmology.2000;107(12):2131-2135.
also a significant increase in tear film breakup time for both
6. Asbell PA,Spiegel S.Ophthalmologist perceptions regarding treatment of moderate-to-severe dry eye:results of a physician
survey.Eye Contact Lens.2010;36(1):33-38.
eyes (P < .005) compared with baseline (Figure 6).
7. The definition and classification of dry eye disease:report of the definition and classification of subcommittee of the internaThese registry study results are consistent with previous
tional dry eye workshop (2007).Ocul Surf.2007;5(2):75-92.
8. Høvding G,Aasved H.Slow-release artificial tears (SRAT) in dry eye disease:report of a preliminary clinical trial.Acta
research on Lacrisert for the treatment of patients with
Ophthalmol.1981;59:842-846.
moderate-to-severe dry eye symptoms.9,10 The registry study 9. Breslin C,Katz J,Kaufman H,Katz I.Slow-release artificial tears.Symposium on Ocular Therapy.1977;10:77-83.
10. Katz J,Kaufman H,Breslin C,Katz I.Slow-release artificial tears and the treatment of keratitis sicca.Ophthalmology.
shows use of the insert for 4 weeks significantly improves
1978;85:787-793.
11. Lamberts D,Langston D,Chu W.A clinical study of slow-releasing artificial tears.Ophthalmology.1978;85:794-800.
symptoms, performance of the activities of daily living, and
12. Werblin T,Rheinstrom S,Kaufman H.The use of slow-release artificial tears in the long-term management of keratitis sicca.
Ophthalmology.1981;88(1):78-81.
quality of life. An improvement of nearly 30% in OSDI and
13. Hill J.Slow-release artificial tear inserts in the treatment of dry eyes in patients with rheumatoid arthritis.Br J Ophthalmol.
other scores for severe dry eye patients suggests that the
1989;73:151-154.
14. Luchs J.Efficacy of hydroxypropyl cellulose ophthalmic inserts (HCOI) in dry eye syndrome (DES) at all levels of severinsert can meaningfully improve the ocular surface for this
ity.Poster presented at:The Association for Research in Vision and Ophthalmology Annual Meeting;May 6,2010;Fort
Lauderdale,FL.
difficult patient group in a relatively short time.
SEPTEMBER 2010 ADVANCED OCULAR CARE 39