Transcript Efficacy and Acceptability of Hydroxypropyl Cellulose Ophthalmic

Efficacy and Acceptability of Hydroxypropyl
Cellulose Ophthalmic Inserts: Subsets of Patients
With Dry Eye Syndrome in a Patient Registry
Bruce H. Koffler, MD
University of Kentucky School of Medicine
The author of this poster has received research funding and travel expense reimbursement from Aton Pharma.
The author would like to acknowledge Susan Terner, MS , and Donald Nelinson , PhD, for support in
preparation of the poster with funding from Aton Pharma.
For interactivity go to View and click Slide Show
Abstract
•
Purpose: To determine efficacy and acceptability of hydroxypropyl cellulose
ophthalmic inserts (HCOI) in subsets of patients with dry eye syndrome (DES).
•
Methods: A multicenter, open-label, prospective registry enrolled 520 patients
with bilateral moderate-to-severe DES. Clinical examinations and Patient
Questionnaires incorporating the OSDI assessed clinical signs, average symptom
severity and frequency, limitations in ADL, and ocular discomfort in various
environments 1 month before baseline and 1 month of treatment. Inserts were
used alone or with existing therapy.
•
Results: There were 418 completers. OSDI scores improved significantly (P<.05)
in contact lens (23.2%), prior cataract surgery (29.2%), and prior refractive
surgery (19.5%) subgroups. OSDI improvement was not significant in cataracts or
glaucoma groups. Discomfort, burning, dryness, grittiness, stinging, and sensitivity
to light were significantly reduced (P<.05) for cataracts, and discomfort and
dryness improved significantly (P<.05) for glaucoma. Blurred vision was the most
commonly reported AE.
•
Conclusions: After 1 month, HCOI as monotherapy or with existing therapy
improved symptoms, ADL performance, and quality of life in moderate-to-severe
DES subsets.
Introduction
Patient subsets
• Contact lens1 factors affecting DES
– Characteristics of lenses
– Protein, lipid and mucin deposits
– Intolerance of lens solutions
• Surgery increases risk of DES, depending on type of procedure
– Cataract surgery2-4
– Laser surgery5
• Glaucoma6 DES is common, associated with type of treatment
– Agents containing benzalkonium chloride and other preservatives
Diagnostic clinical testing is limited by lack of consensus regarding appropriate tests7
• Ocular Surface Disease Index (OSDI) is a validated patient questionnaire that assesses symptom severity
and quality of life8
Artificial lubrication in DES patients is often used
• Artificial tears require frequent administration and may contain preservatives
• Hydroxypropyl cellulose ophthalmic inserts (LACRISERT®, Aton Pharma, Lawrenceville, NJ) are indicated
once daily in patients with moderate-to-severe DES9
– Lubricate eye over 24-hour period, stabilizing precorneal tear film and prolonging tear film breakup time
Purpose of this analysis
• Analysis of larger patient registry done to determine efficacy and acceptability of inserts in patient subsets
Methods: Study Design
• 28-day, 2-visit, multicenter, patient registry
(Tables 1 Registries Vs. Clinical Trials and 2 Criteria for Study Participation)
• Visit 1 (baseline, Day 0)
– BCVA; Slit-lamp examination; DES evaluation of investigator’s choice
(TFBUT, staining, Schirmer’s)
– Patient Questionnaire, including OSDI, to assess DES symptoms and
functioning under various conditions
– Instruction in placement of hydroxypropyl cellulose ophthalmic inserts (HCOI)
(Figure 1 Placing Insert)
• Days 1-28
– Treatment with HCOI as monotherapy, or in addition to current care regimen
• Day 3 ± 1 day
– Telephone contact to assess adverse events (AEs) and proper use of HCOI
– Reinstruction, if necessary
• Visit 2: day 28 ± 3 days
– Repeat clinical evaluation, as in Visit 1
– Patient Questionnaires, including OSDI, to assess DES symptoms,
functioning under various conditions, and satisfaction
– Review of AEs
Table 1
Table 2
Figure 1
Results and Limitations
OSDI
Subgroup analyses found that mean OSDI scores improved significantly (P<0.05) for contact
lens wearers (23.2%), patients with prior cataract surgery (29.2%), and those who had
undergone prior laser surgery (19.5%), but not for patients with cataracts or glaucoma.
Although OSDI scores are normed as a total score, Figures 2 Contact Lens Wearers,
3 Cataract Diagnosis, 4 Cataract Surgery, 5 Laser Surgery, and 6 Glaucoma show changes
in specific OSDI parameters for each subset.
Blurred vision was the most frequent cause for discontinuation in the total population and
increased here, yet patients reported significant improvement in ADLs that require a high
degree of visual acuity: reading, watching TV or movies, working with a computer or ATM,
and driving at night. Table 3 Blurred Vision in Subgroups shows the percentage of patients
affected by blurred vision.
Study Limitations
• Lower level of evidence due to registry design
• No standard of care prescribed by registry protocol
• Inserts often administered as an adjunct to other therapies, but no specific record of other
therapies and their doses was required
• Investigators were not required to record length of time post-surgery for cataract and
refractive surgery patients
• Status of follow-up calls on Day 3 was not always available; omission of a follow-up call
may have affected outcomes
Slit Lamp Photos of CL Patient with Inserts
Select the View additional images/video link on home screen
Table 3
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Conclusions and References
• Registries provide an evaluation of a product under real-life conditions
• The OSDI is a validated instrument that measures DES severity and quality of life
• Total OSDI scores improved significantly for contact lens wearers, patients with
prior cataract surgery, and those who had undergone prior laser surgery, but not for
patients with cataracts or glaucoma patients
• Improvement in the OSDI may reflect better functioning and quality of life
• Blurred vision increased in this analysis, and is likely due to the thickened
precorneal tear film observed after placement of the inserts
• Blurred vision did not interfere with ADLs that require a high degree of visual acuity
• When used as monotherapy or with existing therapy, after 1 month of treatment,
HCOI use improves symptoms, performance of ADL, and quality of life in patients
with moderate-to-severe DES who wear contact lenses, or have had cataract or
refractive surgery
1. Sindt CW, Longmuir RA. Contact lens strategies for the patient with dry eye. Ocul Surf 2007;5(4):294-307. 2. 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(2):75-92. 3. Ram J, Sharma A, Pandav SS, et al.
Cataract surgery in patients with dry eyes. J Cataract Refract Surg 1998;24:1119-1124. 4. Ram J, Gupta A, Brar GS, et al. Outcomes of phacoemulsification in patients with
dry eye. J Cataract Refract Surg. 2002;28:1386-1389. 5. Toda I. LASIK and dry eye. Compr Ophthalmol Update. 2007:8(2):79-85. 6. Leung EW, Medieros FA, Weinreb RN.
Prevalence of ocular surface disease in glaucoma patients. J Glaucoma. 2008;17:350-355. 7. The epidemiology of dry eye disease: Report of the Epidemiology
Subcommittee of the International Dry Eye Workshop (2007). Ocul Surf. 2007;5(2):93-107. 8. Schiffman RM, Christianson MD, Jacobsen G, et al. Reliability and validity of the
ocular surface disease index. Arch Ophthalmol. 2000;118:615-621. 9. LACRISERT [package insert]. Aton Pharmaceuticals, Inc; Lawrenceville, NJ; 2007.
Table 1. Comparison of Registries and Clinical Trials
Comparison
Registries
Clinical Trials
Purpose
To evaluate a product in the real world
To evaluate a product under
controlled conditions
Hypothesis
May be in place, but study is not
designed or powered based on a
specified hypothesis
Prior hypothesis in place with
statistical analysis anticipated by
protocol
Design
No randomization, control arm, or
blinding
Randomized, usually ≥1 control
arm, and blinded
Evaluation
Investigators use their own preferred
methods*
Protocol specifies evaluation
procedures for all participants
Treatment
Investigators add product to current
treatment regimen or change treatment
as they would in professional practice;
therefore, change is incremental beyond
current treatment
Protocol specifies treatment in each
arm of study
Analysis
Ad hoc analysis and post hoc data
mining analyses are acceptable
Ad hoc analyses rare, and post hoc
analyses rarer
*In this study, all investigators used the OSDI, a validated measure of disease severity, consistently to grade DES.
Table 2. Criteria for Study Participation
Inclusion
Exclusion
• Aged 18 years or older
• Clinically significant blepharitis, meibomian gland dysfunction,
or lid margin inflammation
• Diagnosis of bilateral DES
• History of intermittent or
regular artificial tear use or
desire to use artificial tears
within the week prior to
study initiation
• Provided informed consent
• Willing and able to follow all
instructions and attend both
visits
• Currently taking systemic or topical medication used to treat
ongoing bacterial, viral, or fungal ocular infection; active ocular
inflammation; or pre-auricular lymphadenopathy
• LASIK surgery within 12 months of Visit 1 or any other ocular
surgical intervention within 3 months prior to or during the
study period
• Systemic disease or uncontrolled medical condition, that in the
opinion of the investigator, could interfere with study
measurements or compliance
• Use of any new DES therapies throughout the trial that they
had not been previously using
• Taking systemic medications known to cause ocular drying,
unless already on a stable dose within 30 days of Visit 1
• Known allergy and/or sensitivity to hydroxypropyl cellulose
• Participation in an investigational drug or device trial within 30
days of Visit 1
Table 3. Percentage of Patients in Subgroups
Affected by Blurred Vision from Visit 1 to Visit 2
Contact Lens
Wearers
Half or more
of the time
(%)
Cataract
Diagnosis
Cataract
Surgery
Laser
Surgery
Glaucoma
Visit 1
(n=86)
Visit 2
(n=86)
Visit 1
(n=83)
Visit 2
(n=79)
Visit 1
(n=53)
Visit 2
(n=52)
Visit 1
(n=26)
Visit 2
(n=22)
Visit 1
(n=21)
Visit 2
(n=15)
31.3
41.9
49.4
59.5
50.9
59.6
69.3
50
66.7
66.7
Figure 1. Placing the Hydroxypropyl Cellulose
Ophthalmic Insert
Figure 2. Contact Lens Wearers: Change in OSDI Scores*
All of the time
Score
Symptoms
None of the time
* P<0.05, Mean Improvement in Total Score
Difficulty in ADLs
Difficulty in
Environmental
Conditions
Figure 3. Cataract Diagnosis: Change in OSDI Scores
Score
All of the time
Symptoms
Difficulty in ADLs
Difficulty in
Environmental
Conditions
None of the time
Figure 4. Cataract Surgery: Change in OSDI Scores*
All of the time
Score
Symptoms
None of the time
* P<0.05, Mean Improvement in Total Score
Difficulty in ADLs
Difficulty in
Environmental
Conditions
Figure 5. Laser Surgery: Change in OSDI Scores*
Score
All of the time
Symptoms
Difficulty in ADLs
Difficulty in
Environmental
Conditions
None of the time
* P<0.05, Mean Improvement in Total Score
Figure 6. Glaucoma: Change in OSDI Scores
All of the time
Score
Symptoms
None of the time
Difficulty in ADLs
Difficulty in
Environmental
Conditions