Using in Vivo Confocal Microscopy to Assess Cellular Response and Efficacy of Steroid Treatment in Dry Eye Disease
| Status: | Completed |
|---|---|
| Conditions: | Ocular, Ocular |
| Therapuetic Areas: | Ophthalmology |
| Healthy: | No |
| Age Range: | 18 - 89 |
| Updated: | 4/2/2016 |
| Start Date: | February 2014 |
| End Date: | October 2015 |
| Contact: | Cornea Research |
| Email: | Cornea_Research@MEEI.HARVARD.EDU |
| Phone: | 617-573-3313 |
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
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.
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.
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.
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.
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.
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