An observational study in Keratoconjunctivitis Sicca, Dry Eye Syndromes and Ocular Surface Disease, sponsored by Johns Hopkins University. Completed at 1 site in United States. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-01-05.
Sponsored by Johns Hopkins University · Observational
To investigate and compare the burden of dry eye in Sjögren's syndrome dry eye vs non-Sjögren's syndrome dry eye, as well as investigate the diagnostic potential of tear film mucins and various inflammatory cytokines evaluated by tear fluid analysis and impression cytology.
Dry eye is a prevalent ocular disorder worldwide and recognized as one of the most frequent reasons for seeking eye care. Whether locally or systemically initiated, inflammation plays a key role in the pathogenesis of dry eye. Approximately half of the patients with clinically significant dry eye have an underlying systemic inflammatory or autoimmune disease. One serious disease that causes significant dry eye is Sjögren's syndrome (SS). SS is an autoimmune disorder characterized by immune-mediated destruction of the salivary and lacrimal glands, with subsequent development of sicca symptoms. It is one of the most common autoimmune diseases in adults, affecting 1% to 4% of the general population. Approximately 10% of patients with clinically significant dry eye have underlying SS. Currently, the diagnosis of SS among dry eye patients is delayed by about a decade, largely due to lack of awareness and also diversity of patient symptoms and signs, adding to the complexity of diagnosis. Importantly, patients with SS are at risk for many ocular and systemic complications including central nervous system and visceral organ involvement as well as lymphoma. In fact, SS is the autoimmune disease most frequently associated with lymphoma. Therefore, identifying the subset of dry eye patients with SS is relevant.
Diagnosis of SS remains challenging mainly due to the lack of definitive diagnostic tests. The presence of aqueous-deficient dry eye is an integral part of diagnostic criteria for SS. Arguably, the hallmark of SS-related dry eye is conjunctival vital dye staining related to loss or alteration of the ocular surface mucins. A healthy conjunctiva is essential for ocular surface health as conjunctival goblet cells are responsible for secretion of the large gel-forming mucin MUC5AC which plays an important role in maintenance of the tear film on the ocular surface. Reduction of MUC5AC levels in tears of patients with SS has been demonstrated in a single previous study. The investigators also found lower levels of tear MUC5AC, and higher levels of IL-6 an IL-8 in patients with SS-dry eye in comparison to non-SS dry eye and controls. In addition, the investigators found the conjunctival lissamine green staining has a role in differentiating SS versus non-SS dry eye, independently of the dry eye severity.
In addition, increased levels of cytokines such as interleukin (IL)-13, IL-21, and interferon-gamma (IFN-γ) in tears and conjunctiva have previously been shown to correlate with goblet cell loss in SS as well as non-SS-dry eye patients. In murine studies, IFN-γ and tumor necrosis factor alpha (TNF-α) were reported to inhibit MUC5AC secretion in goblet cells stimulated with a cholinergic agonist. Such inhibition correlated with the expression of inflammatory cytokines in the conjunctiva of a mouse model of SS and significantly reduced tear MUC5AC levels. Nevertheless, targeting tear and ocular surface mucins and the relationships to various cytokines in dry eye as a diagnostic or therapeutic area has yet to be extensively studied.
Furthermore, it is well known that patients with SS-related dry eye have much more significant visual complaints than ocular discomfort symptoms arguably due to high corneal punctate erosion scores and diminished corneal subbasal nerve plexus when compared with non-SS dry eye patients. Although the exact mechanism of this is not known, cytokine levels in the tear film might possibly be a contributing factor. Indeed, the worsening of the corneal staining after prolonged gazing, could possibly be attributable to lack of tear film mucin as the investigators demonstrated the correlation between the conjunctival lissamine green staining (a surrogate for goblet cell density which secrete the mucin).
Lastly, although the advent of targeted biological treatments and other factors has led to renewed interest in Sjögren's among rheumatologists and immunologists, its ocular manifestations and burden remain underappreciated. As an example, the most widely used Sjögren's disease activity tool, the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), does not include the extraglandular ocular manifestations of Sjögren's, such as corneal melt/perforation, uveitis, scleritis, retinal vasculitis, and optic neuritis. In addition, the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) only includes one item that addresses the severity of dryness, but this refers to overall dryness and not specifically ocular dryness. Most importantly, these tools do not include any visual symptoms related to dry eye, such as blurred vision and visual or ocular fatigue. The investigators' most recent study points to a significant toll that the ocular manifestations of Sjögren's can have on patients emotionally, physically, and financially, in fact much more pronounced than other manifestation.
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Adult individuals, both male and female, who have been diagnosed with dry eye, as well as adult normal controls will be included.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Signed Institutional Review Board (IRB) approved consent agreeing to terms of the study
The classification criteria are based on the weighted sum of the below 5 items:
each scoring=3
each scoring=1
Individuals who have a total score ≥ 4 for the items above, meet the criteria for primary SS. In other words, for final classification, an individual should have at least one laboratory and one clinical finding.
Additional inclusion criteria for control subjects will include no previous history of dry eye diagnosis, and no known history of disease, verified using a review of systems and past medical history form.
Exclusion Criteria:
History of taking or current use of topical prescription eye drops (including, cyclosporine and as well as any glaucoma eye drops).
Any person treated with glaucoma drops in the past (more than 30 days ago) or who had glaucoma surgery (more than 12 months ago) can be included.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GVHD (graft-versus-host disease)
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients with a previous diagnosis of dry eye made by an eye care specialist and a diagnosis of Sjogren's syndrome made according to the 2016 revised criteria
Diagnostic Test: Questionnaires · Diagnostic Test: Tear fluid sampling · Diagnostic Test: Impression Cytology
Patients with a previous diagnosis of dry eye made by an eye care specialist and no diagnosis of Sjogren's syndrome based on 2016 revised criteria.
Diagnostic Test: Questionnaires · Diagnostic Test: Tear fluid sampling · Diagnostic Test: Impression Cytology
Normal individuals with no previous diagnosis of dry eye or Sjogren's syndrome
Diagnostic Test: Questionnaires · Diagnostic Test: Tear fluid sampling · Diagnostic Test: Impression Cytology
Cognitive ability questionnaires, dry eye symptom questionnaires (Ocular Surface Disease Index, Impact of Dry Eye in Everyday Life, Visual Function Questionnaire-25, Eye Dryness Visual Analog Scale, Visual Fatigue Visual Analog Scale, Visual Tasking Questionnaire, Short Form Survey-36, Profile of Fatigue and Discomfort, European League Against Rheumatism Sjögren's Syndrome Patient Reported Index) will be completed by the subjects
Using microcapillary tubes, 1 microliter of tear fluid will be collected in both eyes of each subject.
Under topical anesthesia, impression cytology sampling will be performed in the temporal bulbar conjunctiva of both eyes of each subject.
Mood Questionnaire
The "Mood Questionnaire" is a self-administered, 7-item questionnaire to measure the mood status. The score ranges from 7 to 28, higher score indicating better mood. The mean and median score in Sjogren's related dry eye group will be compared to non-Sjogren's and normal control group statistically.
Time frame: Once per patient on the day of enrollment.
Center for Epidemiologic Studies Depression Scale (CES-D)
The "Center for Epidemiologic Studies Depression Scale (CES-D)" is a self-administered, 20-item questionnaire to measure the mood and behavioral status. The score ranges between 0 to 60, higher scores indicate the presence of worse symptomology. The mean and median score in Sjogren's related dry eye group will be compared to non-Sjogren's and normal control group statistically.
Time frame: Once per patient on the day of enrollment.
Ocular Surface Disease Index (OSDI)
The "Ocular Surface Disease Index (OSDI)" is a self-administered, 12-item questionnaire to measure the dry eye status.). The score ranges from 0 to 100, higher scores indicate the presence of worse symptomology. The mean and median score in Sjogren's related dry eye group will be compared to non-Sjogren's and normal control group statistically.
Time frame: Once per patient on the day of enrollment.
Visual Functioning Questionnaire-25 (VFQ-25)
The "Visual Functioning Questionnaire-25 (VFQ-25)" is a self-administered, 25-item questionnaire to measure the vision related quality of life. The score ranges from 0 to 100, higher scores indicate better functioning. The mean and median score in Sjogren's related dry eye group will be compared to non-Sjogren's and normal control group statistically.
Time frame: Once per patient on the day of enrollment.
Impact of Dry Eye on Everyday Life (IDEEL)
The "Impact of Dry Eye on Everyday Life (IDEEL)" is a self-administered, 57-item questionnaire to measure the impact of dry eye and dry eye treatments on quality of life. Scores for each dimension ranges from 0 to 100. Higher scores indicate less impact on daily activities/work/emotions; greater bother due to symptoms; greater satisfaction with treatment effectiveness; and less treatment-related bother or inconvenience. The mean and median score in Sjogren's related dry eye group will be compared to non-Sjogren's and normal control group statistically.
Time frame: Once per patient on the day of enrollment.
Visual Tasking Questionnaire (VTQ)
The "Visual Tasking Questionnaire (VTQ)" is a self-administered, 14-item questionnaire to measure the visual functioning status. The composite score for a visual function is defined as the mean response for the items listed for that visual function. The mean and median score in Sjogren's related dry eye group will be compared to non-Sjogren's and normal control group statistically.
Time frame: Once per patient on the day of enrollment.
36 Item Short Form Survey (SF-36)
The "36 Item Short Form Survey (SF-36)" is a self-administered, 36-item questionnaire to measure the self-perceived health status. Scoring ranges from 0 to 100. The lower score indicates higher disability. The mean and median score in Sjogren's related dry eye group will be compared to non-Sjogren's and normal control group statistically.
Time frame: Once per patient on the day of enrollment.
Profile of Fatigue and Discomfort (PROFAD)
The "Profile of Fatigue and Discomfort (PROFAD)" is a self-administered, 19-item questionnaire to measure the fatigue status. Scoring ranges from 0 to 28, with higher scores indicating worse functioning. The mean and median score in Sjogren's related dry eye group will be compared to non-Sjogren's and normal control group statistically.
Time frame: Once per patient on the day of enrollment.
EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI)
The "EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI)" is a self-administered, 3-item questionnaire to measure the dryness, fatigue, and pain status. Scores range from 0 to 30, with higher scores indicating higher severity. The mean and median score in Sjogren's related dry eye group will be compared to non-Sjogren's and normal control group statistically.
Time frame: Once per patient on the day of enrollment.
Visual Fatigue Analogue Scale (VFAS)
The "Visual Fatigue Analogue Scale (VFAS)" is a self-administered, single scale indication, measuring visual fatigue. The score ranges from 0 to 100, with higher score indicating worse fatigue. The mean and median score in Sjogren's related dry eye group will be compared to non-Sjogren's and normal control group statistically.
Time frame: Once per patient on the day of enrollment.
Visual Dryness Analogue Scale (VDAS)
The "Visual Dryness Analogue Scale (VDAS)" is a self-administered, single scale indication, measuring eye dryness. The score ranges from 0 to 100, with higher score indicating worse dryness. The mean and median score in Sjogren's related dry eye group will be compared to non-Sjogren's and normal control group statistically.
Time frame: Once per patient on the day of enrollment.
Impression Cytology of Ocular Surface
Impression cytology samples will be stained using Hematoxiline \& Eosin. Samples will be examined using a light microscope. Mean and median goblet cell counts per high power field in Sjogren's related dry eye group will be compared to non-Sjogren's and normal control group statistically.
Time frame: Once per patient on the day of enrollment.
Inflammatory markers of tear film
Tear film MUC5AC levels will be assessed with enzyme-linked immunosorbent assay (ng/mL), and cytokines \[CXCL9, CXCL11, CXCL13, IL-1, IL-2, IL-6, IL-8, IL-10, IL-12, IL-17, IFN-gamma, and TNF-alpha\] (ng/mL) will be measured using a Luminex assay in a masked fashion. The mean and median level in Sjogren's related dry eye group will be compared to non-Sjogren's and normal control group statistically.
Time frame: Once per patient on the day of enrollment.
Plan to share: No
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