A Simplified Quantitative Method for Assessing Keratoconjunctivitis Sicca From the Sjögren's Syndrome International Registry

Department of Ophthalmology, University of California, San Francisco, San Francisco, California 94143-0422, USA.
American Journal of Ophthalmology (Impact Factor: 3.87). 03/2010; 149(3):405-15. DOI: 10.1016/j.ajo.2009.09.013
Source: PubMed


To describe, apply, and test a new ocular grading system for assessing keratoconjunctivitis sicca (KCS) using lissamine green and fluorescein.
Prospective, observational, multicenter cohort study.
The National Institutes of Health-funded Sjögren's Syndrome International Registry (called Sjögren's International Collaborative Clinical Alliance [SICCA]) is developing standardized classification criteria for Sjögren syndrome (SS) and is creating a biospecimen bank for future research. Eight SICCA ophthalmologists developed a new quantitative ocular grading system (SICCA ocular staining score [OSS]), and we analyzed OSS distribution among the SICCA cohort and its association with other phenotypic characteristics of SS. The SICCA cohort includes participants ranging from possibly early SS to advanced disease. Procedures include sequenced unanesthetized Schirmer test, tear break-up time, ocular surface staining, and external eye examination at the slit lamp. Using statistical analyses and proportional Venn diagrams, we examined interrelationships between abnormal OSS (>or=3) and other characteristics of SS (labial salivary gland [LSG] biopsy with focal lymphocytic sialadenitis and focus score >1 positive anti-SS A antibodies, anti-SS B antibodies, or both).
Among 1208 participants, we found strong associations between abnormal OSS, positive serologic results, and positive LSG focus scores (P < .0001). Analysis of the overlapping relationships of these 3 measures defined a large group of participants who had KCS without other components of SS, representing a clinical entity distinct from the KCS associated with SS.
This new method for assessing KCS will become the means for diagnosing the ocular component of SS in future classification criteria. We find 2 forms of KCS whose causes may differ.

Download full-text


Available from: Steffen Hamann, Mar 17, 2014
  • Source
    • "In this cohort, 28% (228) had all three characteristics and 28% (228) had only dry eye signs and symptoms. It was also observed that only SS patients had the highest ocular surface score compared to non SS subjects.14 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Dry eye from Sjögren's syndrome is a multifactorial disease that results in dysfunction of the lacrimal functional unit. Studies have shown changes in tear composition, including inflammatory cytokines, chemokines, and metalloproteinase. T-lymphocytes have been shown to increase in the conjunctiva and lacrimal glands in patient and animal models. This inflammation is in part responsible for the pathogenesis of the disease, which results in symptoms of eye irritation, ocular surface epithelial disease, and loss of corneal barrier function. There are a number of anti-inflammatory approaches for treating this disease. The current study reviews details of immune response and anti-inflammatory therapies used to control this disease.
    Clinical ophthalmology (Auckland, N.Z.) 08/2014; 8:1447-58. DOI:10.2147/OPTH.S35685
  • Source
    • "The new criteria differ substantially from the 2002 AECG criteria in three ways: they include no subjective ocular and oral symptoms and no functional or morphological tests for the salivary glands; they use a new ocular staining score (OSS) [3] as the only criterion for ocular involvement; and they allow the use of an antinuclear antibody (ANA) titer ≥1:320 plus rheumatoid factor (RF) positivity as an alternative to anti-SSA/SSB antibody positivity for the assessment of systemic autoimmunity. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aims of this study were to assess agreement between the currently used 2002 American-European Consensus Group (AECG) classification criteria and the new 2012 American College of Rheumatology (ACR) criteria for Sjogren's syndrome (SS) and to identify potential sources of disagreement. We studied 105 patients between 2006 and 2013 from the Brittany cohort of patients with suspected SS. AECG criteria were applied using only Schimer's test and unstimulated whole salivary flow (UWSF) to assess objective ocular and oral involvement, since these are the tests most physicians use in clinical practice. Agreement between the two sets of criteria was assessed using Cohen's kappa coefficient. Of those studied, 42 patients fulfilled AECG and 35 ACR criteria. Agreement between the two sets was moderate (kappa = 0.53). Patients fulfilling ACR but not AECG criteria (n = 8) were significantly younger and had shorter symptom durations, but only three of them had SS in the opinion of the evaluating physician. Xerostomia and xerophthalmia (AECG set only) did not discriminate between patients with and without SS. The use of UWSF in the AECG but not the ACR criteria explained part of the disagreement. The serological item in the ACR set (positive rheumatoid factor and antinuclear antibody >=1:320 or anti-SSA/SSB positivity) did not result in classification differences compared to anti-SSA/SSB antibody alone (AECG set). Agreement between ocular staining score >=3 (ACR set) and Schirmer's test <=5 mm/5 min (AECG set) was very low (kappa = 0.14). Agreement was only moderate between ACR and AECG criteria, suggesting these two sets would not select comparable patient populations. An international consensus about which classification criteria should be used in clinical studies is needed.
    Arthritis research & therapy 03/2014; 16(2):R74. DOI:10.1186/ar4514 · 3.75 Impact Factor
  • Source
    • "Subjects were presented with a written document describing the study objectives and sample collection procedures. A quantitative ocular staining score (OSS) developed by the Sjögren’s International Clinical Collaborative Alliance (SICCA) was employed to assess the severity of KCS epitheliopathy [14]. The OSS ranges from 0 to 12. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Keratinizing squamous metaplasia (SQM) of the ocular surface is a blinding consequence of systemic autoimmune disease and there is no cure. Ocular SQM is traditionally viewed as an adaptive tissue response during chronic keratoconjunctivitis sicca (KCS) that provokes pathological keratinization of the corneal epithelium and fibrosis of the corneal stroma. Recently, we established the autoimmune regulator-knockout (Aire KO) mouse as a model of autoimmune KCS and identified an essential role for autoreactive CD4+ T cells in SQM pathogenesis. In subsequent studies, we noted the down-regulation of paired box gene 6 (Pax6) in both human patients with chronic KCS associated with Sjögren's syndrome and Aire KO mice. Pax6 encodes a pleiotropic transcription factor guiding eye morphogenesis during development. While the postnatal function of Pax6 is largely unknown, we hypothesized that its role in maintaining ocular surface homeostasis was disrupted in the inflamed eye and that loss of Pax6 played a functional role in the initiation and progression of SQM. Adoptive transfer of autoreactive T cells from Aire KO mice to immunodeficient recipients confirmed CD4+ T cells as the principal downstream effectors promoting Pax6 downregulation in Aire KO mice. CD4+ T cells required local signaling via Interleukin-1 receptor (IL-1R1) to provoke Pax6 loss, which prompted a switch from corneal-specific cytokeratin, CK12, to epidermal-specific CK10. The functional role of Pax6 loss in SQM pathogenesis was indicated by the reversal of SQM and restoration of ocular surface homeostasis following forced expression of Pax6 in corneal epithelial cells using adenovirus. Thus, tissue-restricted restoration of Pax6 prevented aberrant epidermal-lineage commitment suggesting adjuvant Pax6 gene therapy may represent a novel therapeutic approach to prevent SQM in patients with chronic inflammatory diseases of the ocular surface.
    PLoS ONE 10/2013; 8(10):e77286. DOI:10.1371/journal.pone.0077286 · 3.23 Impact Factor
Show more