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ID PMID Title PublicationDate abstract
27475500 Quantification of fibronectin as a method to assess ex vivo extracellular matrix remodeli 2016 Sep 16 Altered architecture, composition and quality of the extracellular matrix (ECM) are pathological hallmarks of several inflammatory and fibro-proliferative pathological processes such as osteoarthritis (OA), rheumatoid arthritis (RA), fibrosis and cancer. One of the most important components of the ECM is fibronectin. Fibronectin serves as an adhesion molecule anchoring cells to the underlying basement membrane through direct interaction with integrin receptors. Fibronectin hereby modulates the properties of the ECM and affects cellular processes. Quantification of fibronectin remodeling could therefore be used to assess the changes in the ECM that occur during progression of fibro-proliferative pathologies. Ex vivo models are becoming state-of-the-art tools to study ECM remodeling as the cellular composition and the organization of the ECM are preserved. Ex vivo models may therefore be a valuable tool to study the ECM remodeling that occurs during progression of fibro-proliferative pathologies. The aim of this study was to quantify fibronectin remodeling in ex vivo models of cartilage and cancer. A competitive The enzyme-linked immunosorbent assay (ELISA) against the C-terminus of fibronectin was developed (FBN-C). The assay was evaluated in relation to specificity, technical performance and as a marker for quantification of fibronectin in cartilage and cancer ex vivo models. The ELISA was specific and technically stable. Cleavage of tumor tissue with MMP-2 released significantly higher levels of FBN-C compared to tissue with buffer only and western blot analysis revealed that FBN-C recognizes both full length and degraded fibronectin. When ex vivo cartilage cultures were stimulated with the anabolic factor TGFβ and catabolic factors TNF-α and OSM, significantly higher levels of FBN-C were found in the conditioned media. Lastly, FBN-C was released from a cancer ex vivo model. In conclusion, we were able to quantify fibronectin remodeling in ex vivo models of cartilage and cancer. Quantification of fibronectin remodeling could be a valuable tool to understand ECM remodeling in ex vivo models of fibro-proliferative pathologies.
27419047 A comparative proteomics study of a synovial cell line stimulated with TNF-α. 2016 May To elucidate the pathogenesis of rheumatoid arthritis (RA), we used proteomic analysis to determine the protein profile in a synovial cell line, MH7A, established from patients with RA. Proteins were extracted from MH7A cells that were or were not stimulated with tumor necrosis factor-α (TNF-α), and then analyzed on a liquid chromatography/mass spectrometry system equipped with a unique long monolithic silica capillary. On the basis of the results of this proteomic analysis, we identified 2650 proteins from untreated MH7A cells and 2688 proteins from MH7A cells stimulated with TNF-α. Next, we selected 269 differentially produced proteins that were detected only under TNF-α stimulation, and classified these proteins by performing gene ontology analysis by using DAVID as a functional annotation tool. In TNF-α-stimulated MH7A cells, we observed substantial production of plasminogen-activator inhibitor 2 and apoptosis-regulating proteins such as BH3-interacting domain death agonist, autophagy protein 5, apolipoprotein E, and caspase-3. These results indicate that the upregulation of plasminogen-activator inhibitor 2 and apoptosis-regulating proteins in synovial cells in response to TNF-α stimulation might represent a predominant factor that contributes to the pathogenesis of RA.
26925253 Decreased use of glucocorticoids in biological-experienced patients with rheumatoid arthri 2016 INTRODUCTION: Prolonged glucocorticoid use may increase the risk of adverse safety outcomes, including cardiovascular events. The European League Against Rheumatism and the Canadian Rheumatology Association advise tapering glucocorticoid dose as rapidly as clinically feasible. There is a paucity of published data on RA that adequately describe concomitant treatment patterns. METHODS: ACTION (AbataCepT In rOutiNe clinical practice) is a non-interventional cohort study of patients from Europe and Canada that investigated the long-term retention of intravenous abatacept in clinical practice. We assessed concomitant glucocorticoids in patients with established RA who had participated in ACTION and received ≥1 biological agent prior to abatacept initiation. RESULTS: The analysis included 1009 patients. Glucocorticoids were prescribed at abatacept initiation in 734 (72.7%) patients at a median 7.5 mg/day dose (n=692). Of the patients who remained on abatacept at 24 months, 40.7% were able to decrease their dose of glucocorticoids, including 26.9% who decreased their dose from >5 mg/day to ≤5 mg/day. CONCLUSION: Reduction and/or cessation of glucocorticoid therapy is possible with intravenous abatacept in clinical practice.
26629129 Performance evaluation of FlowCytomix assays to quantify cytokines in patients with rheuma 2015 OBJECTIVES: To compare the cytokine profile in RA patients and healthy control by using two methods-FlowCytomix assay and traditional ELISA. METHODS: Cytokine levels were evaluated by FlowCytomix assay and ELISA in serum and supernatants of peripheral blood mononuclear cells (PBMC) cultures with and without stimulation by phytohaemagglutinin (PHA). RESULTS: The levels of IL-6, IL-1β, and TNF-α were significantly higher in sera of RA patients than those of healthy controls. The levels of IL-22, IL-6, IL-1β, TNF-α, and IL-10 were higher in unstimulated PBMC culture supernatant of RA patients than those of healthy controls. PHA stimulation significantly increased the production of proinflammatory cytokines from PBMC with RA patients. Compared with detectable cytokine levels in sera, cytokine concentration in the supernatant of PBMCs was remarkably higher. FlowCytomix and ELISA showed significant correlation in detecting cytokines. However, the FlowCytomix assay detected more cytokines than ELISA. CONCLUSION: The supernatant of PBMCs provide a fine condition for the study of cytokine production because of the lack of interference factors in sera. The FlowCytomix assay is more sensitive than ELISA in detecting cytokines from RA patients. Multiple cytokine signatures using FlowCytomix assay may represent a more realistic approach in the future of personalized medicine in RA.
25600125 Specific IgE positivity against inhalant allergens and development of autoimmune disease. 2015 BACKGROUND: Allergic and autoimmune diseases have been suggested to be inversely associated. We investigated the association between atopy and development of any and specific types of autoimmune disease. METHODS: We included a total of 14,849 individuals from five population-based studies with measurements of atopy defined as specific IgE positivity against inhalant allergens. We followed the participants by linkage to the Danish National Patient Register (median follow-up time 11.2 years). Hazard ratio (HR) and 95% confidence interval (CI) of autoimmune disease were estimated by Cox regression. RESULTS: The risk for atopics versus non-atopics was: for any autoimmune disease (HR = 0.99, 95% CI: 0.83, 1.18), thyrotoxicosis (HR = 0.69, 95% CI: 0.34, 1.37), type 1 diabetes (HR = 1.16, 95% CI: 0.84, 1.60), multiple sclerosis (HR = 1.97, 95% CI: 0.95, 4.11), iridocyclitis (HR = 0.82, 95% CI: 0.38, 1.74), Crohn's disease (HR = 1.03, 95% CI: 0.47, 2.25), ulcerative colitis (HR = 0.93, 95% CI: 0.52, 1.69), psoriasis vulgaris (HR = 1.50, 95% CI: 0.86, 2.62), seropositive rheumatoid arthritis (HR = 0.74, 95% CI: 0.48, 1.14) and polymyalgia rheumatica (HR = 0.79, 95% CI: 0.44, 1.44). CONCLUSIONS: We found no statistically significant associations between atopy and autoimmune disease, but we cannot exclude relatively small to moderate effects - protective or promotive - of atopy on autoimmune disease.
26680367 [Do we still need clinical studies in rheumatology?]. 2016 Feb Despite a large number of approved therapies demonstrating efficacy in the treatment of rheumatic diseases, only 60-85 % of patients with the indications for rheumatoid arthritis are adequately treated in Germany. Additionally, approved therapies for other immune-mediated diseases are often entirely lacking, indicating the great medical need for the development of new innovative therapies in this specialized field. The development of new drugs is expensive due to the high costs of conducting clinical trials in all phases of development up to obtaining approval; therefore, pharmaceutical companies are looking for ways to save costs in the particular developmental stages. Although the classical regions for drug development (i.e. western Europe, the USA and Japan) offer both a high level of data quality and a good infrastructure to conduct clinical trials due to high standards of education and quality, clinical trials are expensive in these regions. Beside high costs, the comparatively low recruitment rates in these regions are one of the main reasons for the shifting of drug developmental stages from classical regions to eastern European, Latin American and Asian countries, which provide services for drug development and high recruitment rates for comparatively less money. However, there are many strong arguments for the participation of regions in western Europe, especially German sites in clinical trials. In this article these arguments are discussed and possible solutions and strategies for conducting and compensation of study centers in Germany for clinical trials in the field of rheumatology are provided.
25819229 Digoxin ameliorates autoimmune arthritis via suppression of Th17 differentiation. 2015 May Digoxin is a cardiac glycoside that is commonly used to treat heart failure. Based on its known anti-inflammatory effect, this study was undertaken to investigate the effect of digoxin on collagen-induced arthritis (CIA) and to delineate the underlying mechanism. Digoxin or vehicle was injected intraperitoneally thrice weekly in mice with CIA, from day 7 or day 35 after immunization to investigate preventive or therapeutic effect, respectively. The incidence and severity of arthritis was evaluated. Digoxin treatment suppressed the incidence of arthritis and joint inflammation in mice with CIA. The expression of IL-17 and other proinflammatory cytokines, including IL-1β, IL-6, TNF-α and IL-21, were markedly reduced in the arthritic joints of digoxin-treated CIA mice. Th17 cells and CD4(+) pSTAT3(+) cells were less frequently observed in the spleen of digoxin-treated CIA mice than controls. The mRNA expression of IL-17 and ROR γt was consistently lower in total splenocytes or draining lymph node cells obtained from digoxin-treated CIA mice. Digoxin also reduced in vitro Th17 differentiation and LPS-stimulated IgG production. The number of osteoclasts in the arthritic joint was lower in digoxin-treated mice, whereas digoxin treatment did not directly suppress in vitro osteoclastogenesis. Our findings suggest that digoxin can regulate Th17 and reciprocally promote Treg cells and suppress joint inflammation and bone erosion in CIA. Digoxin may be a therapeutic option by targeting pathogenic Th17 and immunoglobulin production, for treatment of autoimmune arthritis and other Th17-related diseases.
26883061 ETP-46321, a dual p110α/δ class IA phosphoinositide 3-kinase inhibitor modulates T lymph 2016 Apr 15 Class IA phosphoinositide 3-kinases (PI3Ks) are essential to function of normal and tumor cells, and to modulate immune responses. T lymphocytes express high levels of p110α and p110δ class IA PI3K. Whereas the functioning of PI3K p110δ in immune and autoimmune reactions is well established, the role of p110α is less well understood. Here, a novel dual p110α/δ inhibitor (ETP-46321) and highly specific p110α (A66) or p110δ (IC87114) inhibitors have been compared concerning T cell activation in vitro, as well as the effect on responses to protein antigen and collagen-induced arthritis in vivo. In vitro activation of naive CD4(+) T lymphocytes by anti-CD3 and anti-CD28 was inhibited more effectively by the p110δ inhibitor than by the p110α inhibitor as measured by cytokine secretion (IL-2, IL-10, and IFN-γ), T-bet expression and NFAT activation. In activated CD4(+) T cells re-stimulated through CD3 and ICOS, IC87114 inhibited Akt and Erk activation, and the secretion of IL-2, IL-4, IL-17A, and IFN-γ better than A66. The p110α/δ inhibitor ETP-46321, or p110α plus p110δ inhibitors also inhibited IL-21 secretion by differentiated CD4(+) T follicular (Tfh) or IL-17-producing (Th17) helper cells. In vivo, therapeutic administration of ETP-46321 significantly inhibited responses to protein antigen as well as collagen-induced arthritis, as measured by antigen-specific antibody responses, secretion of IL-10, IL-17A or IFN-γ, or clinical symptoms. Hence, p110α as well as p110δ Class IA PI3Ks are important to immune regulation; inhibition of both subunits may be an effective therapeutic approach in inflammatory autoimmune diseases like rheumatoid arthritis.
27036387 Efficacy and Outcome of Rapid Access Rheumatology Consultation: An Office-based Pilot Coho 2016 Jun OBJECTIVE: Waiting times for first appointments are a major obstacle to timely rheumatology care. To improve access, a cooperative of office-based rheumatologists established an immediate access network, offering brief initial assessments for patients with musculoskeletal problems. METHODS: Patients were assessed at presentation and followed up after 6 months. Data were analyzed regarding demographics, diagnostic accuracy, clinical variables such as pain levels, and care. RESULTS: There were 335 patients assessed in the 6 cooperating practices during dedicated office hours. There were 124 patients (38%) who had a symptom duration of < 3 months. For patients with rheumatoid arthritis (RA), this proportion was 43% (70% for self-referred patients with RA). In the 325 patients available for reassessment after 6 months, initially suspected diagnoses were confirmed in 88%. Confirmation rates were 93% for RA (59 patients) and 84% for spondyloarthritis (SpA; 46 patients). At the followup examination, the visual analog scale for pain in patients with RA had significantly decreased from a median (interquartile range) of 70 (57.75-80) to 27.5 (20-42). For patients with SpA, the decrease was from 65 (50-79) to 30 (20-40). CONCLUSION: The Rapid Access Clinic resulted in a substantial improvement of access to rheumatology assessment. More than one-third of the patients presented < 3 months after symptom onset. Suspected diagnoses of inflammatory rheumatic diseases were confirmed in almost 90%. This initiative demonstrates the feasibility of a rapid access service and indicates high diagnostic accuracy in such a setting. In particular, with respect to early access, it compares favorably with similar hospital-based approaches.
26773106 Development of System-level Performance Measures for Evaluation of Models of Care for Infl 2016 Mar OBJECTIVE: To develop system-level performance measures for evaluating the care of patients with inflammatory arthritis (IA), including rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis, and juvenile idiopathic arthritis. METHODS: This study involved several methodological phases. Over multiple rounds, various participants were asked to help define a set of candidate measurement themes. A systematic search was conducted of existing guidelines and measures. A set of 6 performance measures was defined and presented to 50 people, including patients with IA, rheumatologists, allied health professionals, and researchers using a 3-round, online, modified Delphi process. Participants rated the validity, feasibility, relevance, and likelihood of use of the measures. Measures with median ratings ≥ 7 for validity and relevance were included in the final set. RESULTS: Six performance measures were developed evaluating the following aspects of care, with each measure being applied separately for each type of IA except where specified: waiting times for rheumatology consultation for patients with new onset IA, percentage of patients with IA seen by a rheumatologist, percentage of patients with IA seen in yearly followup by a rheumatologist, percentage of patients with RA treated with a disease-modifying antirheumatic drug (DMARD), time to DMARD therapy in RA, and number of rheumatologists per capita. CONCLUSION: The first set of system-level performance measures for IA care in Canada has been developed with broad input. The measures focus on timely access to care and initiation of appropriate treatment for patients with IA, and are likely to be of interest to other arthritis care systems internationally.
27550416 Modulation of IL-6 induced RANKL expression in arthritic synovium by a transcription facto 2016 Aug 23 Receptor activator of nuclear factor κB ligand (RANKL) is critically involved in bone erosion of rheumatoid arthritis (RA). We previously reported association between younger age at onset of RA and a RANKL promoter SNP that conferred an elevated promoter activity via binding to a transcription factor SOX5. Here we study the regulation of SOX5 levels in relation to RANKL expression in RA synovial fibroblasts (SF) and the development of bone erosion in the collagen-induced arthritis (CIA) mouse. Our data indicated SOX5 levels were higher in synovium and synovial fluid from RA compared to osteoarthritis patients. Pro-inflammatory cytokines upregulated SOX5 and RANKL expression in both primary RA SF and the rheumatoid synovial fibroblast cell line, MH7A. Overexpression of SOX5 resulted in significantly increased RANKL levels, while knockdown of SOX5 resulted in diminished IL-6 mediated RANKL upregulation in MH7A cells. Chromatin immunoprecipitation (ChIP) showed approximately 3-fold enrichment of RANKL-specific DNA in anti-SOX5 immunoprecipitate in IL-6 treated MH7A cells as compared to untreated cells. Locally silencing SOX5 gene significantly diminished RANKL positive cells and bone erosion in CIA mice. These findings suggest SOX5 is an important regulator of IL-6-induced RANKL expression in RA SF.
25427669 The surgical management of atlanto-axial subluxation in juvenile rheumatoid arthritis. 2016 Jul Juvenile idiopathic arthritis (JIA) is a chronic condition affecting patients <16 years of age and can be associated with substantial morbidity. Atlanto-axial subluxation (AAS) is a known complication of JIA and can result in pain, reduced neck motion and neurological compromise. In this paper, we present the case of a 10-year old suffering with JIA and significant AAS; we discuss the management options and present the approach and outcome of treatment for this case.
27022030 Toll/Interleukin-1 Receptor Domain Derived from TcpC (TIR-TcpC) Ameliorates Experimental A 2016 Jun 3 Evasion through immunomodulation is one of the several strategies adopted by pathogens to prolong their survival within the host. One such pathogen, Escherichia coli CFT073, utilizes an immunomodulatory protein, TcpC, to combat the host's innate immune defense. TcpC abrogates the function of MyD88 in macrophages, thus perturbing all the signaling processes that involve this adaptor protein. Although central to various signaling pathways initiated by IL-1, IL-18, and toll-like receptors, the precise contribution of MyD88 to the development of autoimmunity, particularly rheumatoid arthritis, still needs extensive exploration. Herein, by using the toll/interleukin-1 receptor (TIR) domain homologous C-terminal motif of TcpC, i.e. TIR-TcpC, we found MyD88 to be critical for the induction and progression of rheumatoid arthritis through its pivotal role in the development of Th17 cells, the subset of CD4(+) T-cells widely implicated in various autoimmune disorders. The TIR-TcpC mediated inhibition of signaling through MyD88, and subsequent amelioration of experimental autoimmune arthritis was observed to be an outcome of perturbations in the NFκB-RORγt (RAR-related orphan receptor γt) axis.
27509640 Ceramic-on-Ceramic Total Hip Arthroplasty in a Twelve-Year-Old Patient: Case Report with a 2016 Jun Total hip arthroplasty in the juvenile patient with a severely diseasedjoint can provide long-term pain relief and improvement in function. We present a patient with juvenile rheumatoid arthritis who underwent a Mittelmeier ceramic-on-ceramic total hip arthroplasty at age 12 in 1986. The implant provided the patient with a functioning hip for 24 years, but subsequently required revision due to femoral component loosening. This case report represents the longest reported clinical follow-up of noncemented, ceramic-on-ceramic total hip arthroplasty in a juvenile patient and depicts an excellent outcome at 27 years. Our case is also unique in that the Mittelmeier ceramic acetabulum was left in place during revision surgery. In this report, we also describe the senior author's choice of the Mittelmeier hip prosthesis within its historical context and provide a brief review of the literature as it relates to total hip arthroplasty in the juvenile patient.
26602361 Acute pneumonitis in a patient with adult-onset disease after toclizumab treatment with go 2016 Nov Pulmonary involvement in the form of acute pneumonitis in adult-onset Still's disease (AOSD) is an uncommon manifestation, with few cases reported in the literature. We report the case of a 61-year-old male with 3 years of AOSD evolution, treated with methotrexate (MTX) and half-dose corticosteroids, which debuted with symptoms of fever, dyspnea and dry cough after 3 weeks of receiving the first dose of tocilizumab (TCZ). In the follow-up study showed leukocytosis with left shift, elevated serum ferritin and C-reactive protein standard. The chest CT scan showed ground-glass pattern predominantly in central and upper lobes and the BAL shows an increase in the percentage of lymphocyte with normal subpopulations and negative cultures. MTX and TCM were suspended, prednisone was increased to 30mg/day and within a week Anakinra 100mg/day SC was iniciated, noting in a few days a progressive clinical, analytical and radiological improvement.
26350919 Crying Without Tears: Dimensions of Crying and Relations With Ocular Dryness and Mental We 2016 Mar This study examined dimensions of crying and its relations with ocular dryness and mental well-being in patients with Sjögren's syndrome, a systemic autoimmune disease with dryness as primary symptom. Three-hundred patients with Sjögren's syndrome completed questionnaires on crying, dryness, and well-being. The crying questionnaire revealed four dimensions: "Cryability" (comprising both crying sensibility and ability to cry), Somatic consequences, Frustration, and Suppression. Compared to 100 demographically-matched control participants from the general population, patients scored low on Cryability and high on Somatic consequences and Frustration. The crying dimensions generally showed significant but weak associations with ocular dryness and mental well-being in patients. This is the first quantitative study indicating that crying problems are more common in patients with Sjögren's syndrome than in the general population. Perhaps, patients who experience problems with crying could be helped to rely on other ways of expressing emotions than crying in tear-inducing situations.
26155865 [A case of asymptomatic Sjögren's syndrome who developed interstitial pneumonia during mo 2015 Jul A 67-year-old woman was diagnosed with ileocolic Crohn's disease at 61 years of age. Remission had been induced by the monoclonal antibody adalimumab, and maintenance therapy had continued since her diagnosis. However, she developed respiratory symptoms, including a dry cough. A chest CT scan revealed interstitial shadows in the lower pulmonary lobes. Although no sicca symptoms were noted, she was serologically positive for both anti-Sjögren's syndrome-related antigen A and B antibodies, and salivary gland biopsy showed lymphocytic infiltration. Consequently, she was diagnosed as having asymptomatic Sjögren's syndrome. Infection or drug-induced pulmonary disease was considered unlikely, and the interstitial pneumonia was considered an extra-glandular presentation of Sjögren's syndrome. Thus, interstitial shadows, which appear during immunotherapy for Crohn's disease, could indicate asymptomatic Sjögren's syndrome; clinicians should consider this rare clinical picture when assessing such a patient.
25849850 Rapid decrease in salivary epidermal growth factor levels in patients with Sjögren's synd 2015 OBJECTIVES: To assess changes in salivary epidermal growth factor (EGF) levels within three years and investigate the correlation between these changes and the severity of intraoral manifestations in patients with Sjögren's syndrome (SS). METHODS: Twenty-three SS patients (14 primary SS and 9 secondary SS) and 14 controls were followed up for three years. Salivary EGF concentration was measured using an enzyme-linked immunosorbent assay, and intraoral manifestations were evaluated using a short version of the Oral Health Impact Profile (OHIP-14). Changes in salivary flow rate, EGF level, and severity of intraoral manifestations were analyzed, along with associations among them. RESULTS: The OHIP-14 score significantly increased and the total salivary EGF output significantly decreased after three years in the SS group (10.2 ± 8.8 vs. 12.6 ± 9.2, p = 0.040; 10158.4 ± 9820.9 vs. 8352.8 ± 7813.3 pg/10 min, p = 0.032), though the salivary flow rate did not change. The decrease in total EGF output was especially high in patients with long disease duration and poor oral health-related quality of life (OHRQoL). In patients with poor OHRQoL, the change in total EGF output significantly correlated with the OHIP-14 score (r = - 0.847, p = 0.008). However, there was no correlation between the change in salivary flow rate and the OHIP-14 score. CONCLUSIONS: The rapid decrease in salivary EGF level contributes to the progression of intraoral manifestations of SS.
25467751 Air particulate matter exacerbates lung response on Sjögren's Syndrome animals. 2015 Feb Epidemiological studies have associated air particulate matter (PM) inhalation with a decline in lung function and increased morbo-mortality due to cardiorespiratory diseases, particularly in susceptible populations. Sjögren's Syndrome (SS) is a chronic autoimmune disease characterized by cellular infiltration in exocrine glands and extraglandular tissue, being the respiratory tract an important target. We evaluated the effect of PM on the airways of NOD mice, which develop SS and BALB/c mice. BALB/c or NOD mice (2-3 months) were randomized in two groups and exposed to intranasal instillation either with saline (control) or ROFA solution (1mg/kg body weight). After 24h, mice were euthanized in order to perform lung histology, or measure total cell number (TCN), differential cell count (DCC) and superoxide anion generation in the bronchoalveolar lavage (BAL) fluid. BALB/c mice showed normal histoarchitecture, while NOD mice showed lymphocytic peribronchial infiltrates. ROFA exposure affected the respiratory tract from both BALB/c and NOD mice, with a significant increase in the TCN (p<0.05) and generation of O2(-) (p<0.05), as well as an imbalance in the DCC (p<0.05). All histological observations correlated with the cellular parameters evaluated. Lesions in NOD mice were more severe than those of BALB/c, showing cellular infiltration in the alveoli and leading to a greater decrease in the alveolar space. We have proved that in this experimental Sjögren's Syndrome animal model (NOD mice); airborne pollution exacerbates pre-existing pulmonary lesions. These findings show experimental evidence on the harmful effects of airborne pollution on the airways of patients with Sjögren's Syndrome.
25308575 Effect of non-invasive tear stability assessment on tear meniscus height. 2015 Mar PURPOSE: To investigate the effect of non-invasive tear stability assessment with forced eye opening on the lower tear meniscus. METHODS: Twenty-three eyes of 23 patients with aqueous-deficient dry eye and 23 eyes of 23 normal subjects were enrolled. All subjects underwent imaging with a Keratograph 5M equipped with a modified tear film scanning function. Lower tear meniscus images were captured, and tear meniscus height (TMH) was measured with an integrated ruler before and after non-invasive Keratograph break-up time (NIKBUT) measurements in each subject. Subjects were instructed to keep their eyes open as long as possible during NIKBUT measurements, and the recording was discontinued at the next blink. RESULTS: The TMH values of the normal and dry eye groups were 0.20±0.05 mm and 0.14±0.03 mm, respectively, at baseline. The TMH values of dry eyes were significantly smaller than those of normal eyes (p<0.001). Significant increases in TMH values were observed in both normal (0.10±0.12 mm) and dry eyes (0.04±0.09 mm) with the NIKBUT measurement (p<0.001, p=0.039). A moderate negative correlation was observed between increased TMH and baseline TMH in dry eyes (r=-0.44, p=0.03), whereas no correlation was observed in normal eyes (r=0.04, p=0.85). CONCLUSIONS: Forced eye opening required for the non-invasive tear stability assessment influences the TMH measurement possibly due to reflex tear secretion, even in patients with aqueous-deficient dry eye. TMH should be assessed before tests that require forced eye opening.