Using in Vivo Confocal Microscopy to Assess Cellular Response and Efficacy of Steroid Treatment in Dry Eye Disease

Dry Eye Syndrome Clinical Trial

Official title:

The Utility of in Vivo Confocal Microscopy to Assess Cellular Response and Efficacy of Long-term Topical Steroid Treatment in Patients With Dry Eye Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02106377
• Other study ID #: 537897
• Status: Recruiting
• Phase: N/A
• First received: April 3, 2014
• Last updated: April 7, 2014
• Start date: February 2014
• Est. completion date: October 2015

Study information

• Verified date: April 2014
• Source: Massachusetts Eye and Ear Infirmary
• Contact: Cornea Research
• Phone: 617-573-3313
• Email: Cornea_Research[@]MEEI.HARVARD.EDU
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Current steroid therapy in dry eye disease (DED) is comprised of a 2 week duration of pulse therapy, administered twice daily (to avoid adverse effects associated with long-term steroid use). This timeframe is often too short to meaningfully resolve the inflammation associated with DED. Thus, corneal specialists, including here at MEEI, have begun using steroid treatment of at least 6 weeks with tapered dosing.

In vivo confocal microscopy (IVCM) is a novel imaging technology that allows the visualization and quantification of certain corneal features associated with DED, such as hyperfluorescent superficial epithelial cells, immune dendritic cells, and sub-basal nerves. Recent cross-sectional studies have begun to shed light on the correlation of these features with traditional outcome measures typically assessed in DED, such as corneal and conjunctival staining, Schirmer's testing, tear break-up time (TBUT), and symptom questionnaires. However, longitudinal studies using IVCM to demonstrate how steroid treatment affects the corneal epithelial cells, dendritic cells and nerves are largely lacking. Furthermore, studies on the safety and efficacy of a 6 week tapered dosing steroid regimen are also lacking.

Description:

Recent studies have shown that inflammation plays an important role in the pathogenesis of Dry Eye Disease (DED). Ocular surface inflammation often exacerbates the subject's signs and symptoms, and results in an increase in the immune cells and other inflammatory mediators located in the ocular surface. Dry eye disease is one of the most commonly encountered ophthalmic disorders. It is a multifactorial disease of the ocular surface and tear film, characterized by symptoms of eye irritation, tear instability and vision impairment. Despite being very common, standardized therapy is not available.

Due to the underlying inflammation associated with DED, anti-inflammatory steroid medications are used for the treatment of DED. "Soft steroids" are often preferred because their chance of increasing intraocular pressure (IOP) is lower than other steroids. One of the "soft steroids" that is commonly used for the treatment of inflammation associated with ocular surface disease is loteprednol etabonate 0.5% ophthalmic suspension (Lotemax, Bausch & Lomb, Inc).

Current steroid therapy in DED is comprised of pulse therapy (to avoid adverse events associated with long-term steroid use) of usually 2 weeks duration, administered BID. This timeframe is often too short to meaningfully resolve the inflammation associated with DED. More recently steroid treatment of at least 6 weeks with tapered dosing has been advocated.

Lotemax, an FDA-approved medication for ocular inflammatory disease, is commonly used to treat inflammation associated with DED with a regimen of twice daily for 2 weeks. However, because DED is a chronic disease, this short duration of steroid therapy may not be enough to meaningfully resolve the inflammation associated with DED. Thus, corneal specialists, including here at MEEI, have begun using Lotemax for at least 6 weeks with tapered dosing. This study has been designed to evaluate the effects of this tapering regimen on inflammation associated with DED.

Clinical signs and symptoms are used to evaluate the efficacy of a treatment for DED, including Schirmer's test, tear break-up test, corneal fluorescein staining, and conjunctival lissamine green staining. However, none of these tests evaluate the underlying inflammatory and immune response changes in DED. Therefore, to determine the efficacy of any treatment for DED, it is ideal to evaluate these underlying changes in addition to the clinical parameters.

In vivo confocal microscopy (IVCM) is a novel imaging technology that allows the visualization and quantification of corneal structures at the cellular level. IVCM has recently been used to evaluate the corneal changes in DED, such as hyperfluorescent superficial epithelial cells, immune dendritic cells, and sub-basal nerves.

Therefore, in this randomized clinical trial, IVCM images will be used to determine the changes in corneal immune cells and nerves during a 6-week taper regimen of Lotemax versus Soothe Tired Eyes Lubricant Eye Drop (Glycerin 1.0%, Bausch & Lomb Inc.) (an artificial tear) for treatment of inflammation associated with DED.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: October 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 89 Years

Eligibility

Inclusion Criteria:

• Age 18-89 years.

• Willing and able to provide written informed consent.

• Willing and able to comply with study assessments for the full duration of the study.

• Diagnosis of dry eye disease based on the followings:

1. Symptoms of dry eye disease such as foreign body sensation, burning, stinging, light sensitivity for at least 6 months.

2. Two or more of the following objective signs:

• Schirmer test with anesthesia <10 mm at 5 minutes [mean Schirmer between eyes.

• Tear break-up time (TBUT) of <10 seconds.

• Corneal fluorescein staining of 4 (NEI grading scheme, 0-15) in at least one eye

• Lissamine green staining of the nasal and temporal conjunctiva (NEI grading scheme, 0-18) in at least one eye

• Corneal dendritiform cell count by confocal microscopy of >=75/mm2 (13 immune cells per image)

• In good stable overall health.

Exclusion Criteria:

• Central corneal subbasal dendritic cell count by in vivo confocal microscopy of <75/mm2 in both eyes

• Active ocular allergies

• Active allergies to steroids, aminoglycosides, or benzalkonium chloride (BAK)

• History of contact lens wear within 3 months before enrollment.

• Intraocular surgery or ocular laser surgery within 3 months before enrollment.

• History of ocular infection within 3 months before enrollment.

• History of topical or systemic steroid treatment (Loteprednol (other than Lotemax suspension used in our study), Difluprednate, Fluorometholone, Prednisolone, Dexamethasone, Triamcinolone, Rimexolone, Medrysone) within 1 month before enrollment. In case of topical steroid use, a wash-out period of 1 month is required.

• History of increased intraocular pressure after using topical steroids (steroid responsive)

• History of systemic immunosuppressive treatment within 1 month before enrollment.

• History of any change in the frequency of topical cyclosporine or oral tetracycline compounds (tetracycline, doxycycline, and minocycline) within 1 month before enrollment.

• Any condition (including language barrier) that precludes subject's ability to comply with study requirements including completion of study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dry Eye Syndrome
• Dry Eye Syndromes
• Eye Diseases
• Keratoconjunctivitis Sicca

Intervention

Drug:
• loteprednol etabonate (Lotemax)
Lotemax (loteprednol etabonate) 0.5% is a prescription-only, preserved ophthalmic suspension supplied by Bausch & Lomb, Inc. Lotemax (loteprednol etabonate) 0.5% has been approved by the FDA for treatment of ocular inflammation with a maximum dosing frequency of 24 drops per eye per day. It is a C-20 ester-based corticosteroid, with a potent anti-inflammatory efficacy, but decreased impact on intraocular pressure (IOP) compared to other corticosteroids, which may increase IOP. The medication will be applied topically to both eyes for 6 weeks with the following regimen: four times a day for 2 weeks, twice daily for 2 weeks, and once daily for 2 weeks.
• Soothe Tired Eyes Lubricant Eye Drop
Soothe Tired Eyes Lubricant Eye Drop (Bausch & Lomb Inc.) is a preserved artificial tear whichis used to relieve the dryness of the eye and to prevent further irritation. Its active ingredient is glycerin 1%. The artificial tear will be applied topically to both eyes for 6 weeks with the following regimen: four times a day for 2 weeks, twice daily for 2 weeks, and once daily for 2 weeks.

Locations

Country	Name	City	State
United States	Massachusetts Eye and Ear Infirmary	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts Eye and Ear Infirmary

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the efficacy of Lotemax as compared to Soothe Tired Eyes Lubricant Eye Drop , using clinical and in vivo confocal microscopic findings.		6 weeks	No