Ocular Micro-vascular Research Base on Functional Slip Lamp Biomicroscopy
Keywords
Abstract
Description
Dry eye (DE) is a growing public health concern that affects not only the visual function but also the quality of life of patients. In 2017, the International DE Study Workshop (DEWSII) adjusted the definition of DE by particularly emphasizing the inflammation in the ocular surface, and this adjustment represented a major shift in the understanding of dry eye disease (DED) pathogenesis and the facilitation of DED treatment.1,2 The recurrence of chronic and low-grade inflammation plays an important role in long-term disease progression and gradually deteriorates the ocular surface.3 Previous studies have concluded that the inflammatory response is involved in the pathological process of DE.4-7 The concentrations of IL-1α and mature IL-1ß in the tear fluid are increased.4,5 The activity of MMP-9, a suggested biomarker associated with ocular surface diseases including DE, is significantly elevated in Meibomian gland dysfunction (MGD), Sjögren's syndrome (SS) and aqueous tear deficiency (ATD).6 Other studies have indicated that inflammatory mediators such as IL-6, IL-8 and TNFα are expressed proportionally to the severity of DE symptoms, indicating the involvement of inflammation.7 The identification of inflammation as a major factor in DE informs the treatment strategy, including anti-inflammatory medication, which results in improvements to the ocular surface condition and to ocular comfort in DED patients.8,9 A series of studies have demonstrated improvements in the subjective and objective signs and symptoms of DE after anti-inflammatory and immunomodulatory therapies.8-11 To monitor the status of ocular surface inflammation and the ocular surface condition, traditional assessments, namely, evaluation of conjunctival hyperemia12 and corneal fluorescein staining using a slit lamp biomicroscope, are used. However, these methods are subjective and volatile and may not be sensitive indicators of the disease stage and treatment efficacy.13 A number of new tests have been used to distinguish inflammation.13-15 These new technologies include corneal confocal microscopy,15 conjunctival impression cytology16 and inflammatory tear-film cytokine tests in research and in the clinic.17 These newly implemented techniques have several limitations. Corneal confocal microscopy is a structure-based instrument with a narrow view of 400 × 400 µm2 that is limited to localization and cell counting. Conjunctival impression cytology16 and inflammatory tear-film cytokine tests19 are not routinely used, possibly due to the invasiveness, high cost and discomfort of these techniques.5,18 Therefore, the development of new methodologies to noninvasively and subjectively evaluate the inflammation status of the ocular surface is crucial.
The microvascular system of the bulbar conjunctiva can be easily accessed. The release of inflammatory cytokines on the ocular surface can cause vasodilation, which may result in alterations to the conjunctival microcirculation.19 Cheung et al. used a computer-assisted intravital microscope to evaluate vasculopathies of the conjunctival vessels and identified microvascular abnormalities in patients with diabetes20 and in patients who wore contact lens.21 Schulze et al. have also performed `evaluations of the redness of the bulbar conjunctiva using fractal analysis and photometry.22 However, these studies did not directly measure the microcirculation. The microcirculation is an important aspect of the vascular system, may directly represent the hemodynamic response to ocular surface inflammation and may exhibit more sensitivity for monitoring vascular responses to anti-inflammatory treatment. Recently, Jiang et al. developed a functional slit-lamp biomicroscope that could be used to measure the conjunctival blood flow velocity (BFV) and vessel diameter.23 The goal of the present study was to characterize the microvasculature and microcirculation in the bulbar conjunctiva of DE patients in response to anti-inflammatory treatment.
Dates
Last Verified: | 10/31/2018 |
First Submitted: | 11/29/2017 |
Estimated Enrollment Submitted: | 11/18/2018 |
First Posted: | 11/19/2018 |
Last Update Submitted: | 11/18/2018 |
Last Update Posted: | 11/19/2018 |
Actual Study Start Date: | 06/29/2017 |
Estimated Primary Completion Date: | 06/29/2020 |
Estimated Study Completion Date: | 06/29/2020 |
Condition or disease
Intervention/treatment
Drug: Dry eye group
Device: Functional Slit-Lamp Biomicroscopy
Phase
Arm Groups
Arm | Intervention/treatment |
---|---|
Experimental: Dry eye group The recruitment of subjects met the criteria of DEWS. Each subject received treatment based on increasing severity according to the expert consensus for the treatment of DE inflammation. For moderate levels of severity, topical anti-inflammatory agents (0.1% Fluorometholone) were administered twice daily and then gradually less frequently until inflammation was controlled. For severe DE, the approach was similar to that of the moderate level but with an increased concentration and treatment frequency of the anti-inflammatory agents (0.1% Fluorometholone, 4 times daily). Topical 0.05% tacrolimus twice daily when DE was extremely severe. Functional Slit-Lamp Biomicroscopy were administrated to collected data from this group. | Drug: Dry eye group Fluorometh010neEyeDrops:
Brand names: Allergan Pharmaceuticals Ireland, Serial number: J20130061, NDC 60758-880-05. Tacrolimus Brand names: Senju Pharmaceutical Co., Ltd. Fukusaki Plant Serial number: H20130452 |
Experimental: Control group Normal health subject without drug intervention, Functional Slit-Lamp Biomicroscopy were administrated to collected data from this group. |
Eligibility Criteria
Ages Eligible for Study | 18 Years To 18 Years |
Sexes Eligible for Study | All |
Accepts Healthy Volunteers | Yes |
Criteria | Inclusion Criteria: - age ≧ 18 years - Ocular Surface Disease Index (OSDI) ≧ 12. - A 5-min Schirmer I test (ST) result showing less than 5 mm of moisture on the strip. - A noninvasive average tear-film break-up time (NI-avBUT) less than 5 s. Exclusion Criteria: - Patients were excluded if they had an eye infection, injury, non-DE ocular inflammation, ocular surgery within the last 6 months, or any concurrent treatment that might interfere with the interpretation of the study results (systemic corticosteroids, immunosuppressive therapy, or hormonal replacement therapy). Patients were also excluded if they had an uncontrolled disease, had a significant illness or were pregnant or lactating. |
Outcome
Primary Outcome Measures
1. Conjunctival microvascular blood flow velocity [Baseline]
2. Conjunctival microvascular blood flow velocity [30 days after commencement of treatment]
3. Conjunctival microvascular blood flow velocity [60 days after commencement of treatment]
4. Conjunctival microvascular diameter [Baseline]
5. Conjunctival microvascular diameter [30 days after commencement of treatment]
6. Conjunctival microvascular diameter [60 days after commencement of treatment]
7. Conjunctival microvascular blood flow rate [Baseline]
8. Conjunctival microvascular blood flow rate [30 days after commencement of treatment]
9. Conjunctival microvascular blood flow rate [60 days after commencement of treatment]
10. The hyperemia index [Baseline]
11. The hyperemia index [30 days after commencement of treatment]
12. The hyperemia index [60 days after commencement of treatment]
Secondary Outcome Measures
1. Non-invasived tear-film break-up time [Baseline]
2. Non-invasived tear-film break-up time [30 days after commencement of treatment]
3. Non-invasived tear-film break-up time [60 days after commencement of treatment]
4. Corneal Fluorescein Staining [Baseline]
5. Corneal Fluorescein Staining [30 days after commencement of treatment]
6. Corneal Fluorescein Staining [60 days after commencement of treatment]
7. Schirmer I test [Baseline]
8. Schirmer I test [30 days after commencement of treatment]
9. Schirmer I test [60 days after commencement of treatment]