Correlations among symptoms, signs, and clinical tests in evaporative-type dry eye disease caused by Meibomian gland dysfunction (MGD).

PURPOSE: To evaluate changes in symptoms, objective tests, and signs after medical treatment of subjects with evaporative-type dry eye disease (EDE) caused by Meibomian gland dysfunction (MGD), and to analyze correlations among symptoms, signs and test results in the worse eyes (W-eyes) of the subjects. METHODS: Prospective clinical study of 21 symptomatic subjects with EDE caused by MGD. Subjects who were diagnosed with EDE in a first visit were treated for 6 weeks and re-evaluated in a second visit. The differences between initial and second visits were evaluated. Correlations among clinical symptoms, signs, and test results were performed using the data of the W-eyes. Variables evaluated included: dry eye symptoms, best corrected visual acuity (BCVA), contrast sensitivity, conjunctival hyperemia, phenol red thread test, tear break-up time (TBUT), tear meniscus height (TMH), corneal fluorescein and conjunctival rose Bengal staining, tear lysozyme concentration, Schirmer test, and lid margin assessment. RESULTS: All items evaluated improved after treatment, but only conjunctival hyperemia and TMH improved significantly. TBUT and lid margin changes improved, but still remained abnormal. There were significant correlations among symptoms questionnaires and some clinical tests (TBUT, conjunctival hyperemia, TMH, and conjunctival rose Bengal staining). CONCLUSION: Despite the instability of the tear film and lid margin alterations that continued after treatment, subjects with MGD improved symptomatically. The low degree of correlations among W-eye signs, symptoms, and tests reflects the independency of symptoms and signs in this complex pathology.

Differential cell proliferation, apoptosis, and immune response in healthy and evaporative-type dry eye conjunctival epithelia.

PURPOSE: To assess cell viability and cell cycle kinetics of the conjunctival epithelium and to identify intraepithelial lymphocyte (IEL) subsets in patients with evaporative-type dry eye disease (ev-DED) caused by meibomian gland dysfunction and in healthy subjects. The effect of topical treatment and correlations between clinical symptoms and signs and epithelial and immune variables were also determined. METHODS: Inferior fornix and tarsal conjunctival cells were collected by brush cytology (BC) from patients with mild to moderate ev-DED (n = 23) before and after 2 months of treatment that included lid hygiene, artificial tears, and a 3-week course of topical unpreserved steroids. Healthy subjects (n = 17) served as controls. Two symptom questionnaires were self-answered, and multiple DED-related clinical tests were performed. Epithelial or immune lineage, IEL subtypes, cell viability, apoptosis, and cell cycle stage of the BC-recovered cells were determined by flow cytometry. RESULTS: Conjunctival cell viability was dramatically decreased in ev-DED patients compared with controls. For both groups, two different cell populations, differentiated by cell size and complexity, were present in the apoptosis assay. After 2 months of treatment, 87% of subjects subjectively improved, CD8 cells increased, and CD4 cells and the CD4/CD8 ratio significantly decreased. The pretreatment and posttreatment proliferative capacity of the conjunctival epithelium was significantly lower in ev-DED patients than in healthy controls. CONCLUSIONS: The viability and proliferative capacity of ev-DED patient conjunctival cells were reduced, suggesting a potential role for these parameters as disease biomarkers.

Tear cytokine and chemokine analysis and clinical correlations in evaporative-type dry eye disease.

PURPOSE: Inflammatory molecules have been demonstrated in the tear film of patients with severe dry eye disease (DED). However, little attention has been paid to the most frequent moderate forms of DED. This study analyzes tear cytokine levels and their clinical correlations in patients with moderate evaporative-type DED due to meibomian gland disease (MGD). METHODS: Twenty three evaporative-type DED patients (46 eyes) of mild-to-moderate intensity and nine healthy subjects (18 eyes) were recruited. Two symptom questionnaires were self-answered and multiple DED-related clinical tests were performed. Unstimulated tears from each eye were isolated and were not pooled. Levels of 15 cytokines and chemokines were measured by multiplex bead analysis, compared with control levels, and correlated with clinical tests. RESULTS: Fourteen out of the 15 molecules were reliably detected in 1 microl of unstimulated tears from DED patients. Epidermal growth factor (EGF), fractalkine/CX3CL1, interleukin (IL) 1-receptor antagonist (Ra), IL-8/CXCL8, interferon inducible protein (IP)-10/CXCL10, and vascular endothelial growth factor (VEGF) were found in 94%-100% of samples; IL-6 in 65% (significantly more detected in older patients); IL-1beta, interferon gamma (IFN-gamma), and IL-10 in 30%-48%; IL-17 in 13%; granulocyte macrophage colony stimulating factor (GM-CSF), IL-13, and tumor necrosis factor alpha (TNF-alpha) in 2%-9%; and IL-5 was never detected. EGF, fractalkine/CX3CL1, IL-1Ra, IP-10/CXCL10, and VEGF levels were significantly increased compared to normal controls. Pain was correlated with IL-6 and IL-8/CXCL8. Tear break-up time correlated inversely with IL1-Ra. Schirmer test and tear lysozyme levels negatively correlated with IL-1Ra, IL-8/CXCL8, fracktalkine/CX3CL1, IL-6, IP-10/CXCL10, and VEGF had the same tendency. Conjunctival staining correlated negatively with EGF and positively with IL-6. CONCLUSIONS: In this sample of moderate evaporative-type DED patients, five inflammatory molecules were elevated. Fracktalkine was demonstrated to be present and elevated in tears in human DED. IL-1Ra, IL-6, IL-8/CXCL8, and EGF levels correlated with pain and with clinical parameters measuring tear stability, tear production or ocular surface integrity. These results suggest that inflammation plays a role not only in severe DED but also in moderate evaporative DED.