Signs and Symptoms of Dry Eye in Keratoconus Patients: A Pilot Study

Carracedo, Gonzalo; Recchioni, Alberto; Alejandre-Alba, Nicolás; Martín-Gil, Alba; Crooke, Almudena; Morote, I. Jiménez-Alfaro; Pintor, Jesús

doi:10.3109/02713683.2014.987871

Cited by 57 publications

(78 citation statements)

References 42 publications

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“…The activation of fibroblasts during keratoconjunctivitis further supports the use of this cell type. 44 In addition, in inflammation-based diseases such as DE, loss of TGF-b2-expressing goblet cells in the ocular surface 45 suggests an involvement of other cell types in the immunomodulatory process. Recent research indicates that fibroblasts can contribute to the inflammatory reaction by releasing inflammatory modulators in response to different cytokines.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Cytokine-Mediated Regulation of Thrombospondin-1 and CD36 in Conjunctival Cells

Soriano-Romaní

Contreras-Ruiz

García-Posadas

et al. 2015

Journal of Ocular Pharmacology and Therapeutics

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Purpose: Increased expression of transforming growth factor-b2 (TGF-b2) is reported in the conjunctiva of dry eye patients with no increase of anti-inflammatory activity of TGF-b2. Our aim was to compare the expression of molecules involved in TGF-b2 activation, thrombospondin-1 (TSP-1) and CD36, during murine and human conjunctival inflammation. Methods: Human conjunctival tissue from cadaveric donors, human conjunctival epithelial primary cells and fibroblasts, and murine conjunctivas were immunostained for TSP-1, CD36, or TGF-b2. Inflamed conjunctival tissues were obtained from C57BL/6 wild-type (WT) mice induced to develop experimental dry eye (EDE) with 10 days of desiccating conditions and scopolamine injections and TSP-1-deficient (TSP1 -/ -) mice, which spontaneously develop Sjögren's syndrome-associated conjunctival inflammation with age. Immunostaining intensities were compared using ImageJ software. Cultures of human conjunctival fibroblasts were stimulated with IL-1b and both secreted protein and message levels of TSP-1, CD36, and TGF-b2 were analyzed. Results: TSP-1 and CD36 were detectable in human and murine conjunctival tissues as well as primary conjunctival epithelial cells and fibroblasts. Increased conjunctival immunostaining of TGF-b2 and reduced CD36 were detected in EDE mice compared with WT mice. Interestingly, increased TGF-b2 and CD36 conjunctival immunostaining was detected in TSP1-/ -mice. The expression of TSP-1 and CD36 was downregulated in IL-1b-stimulated conjunctival fibroblasts at both the protein and message level, while active TGFb2 was undetected. Conclusions: The absence or reduced expression of either of the molecules involved in TGF-b2 activation supports proinflammatory conditions in the conjunctiva. Changes in TSP-1 and CD36 may serve as potential biomarkers of conjunctival inflammation.

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Section: Discussionmentioning

confidence: 99%

Inflammatory Cytokine-Mediated Regulation of Thrombospondin-1 and CD36 in Conjunctival Cells

Soriano-Romaní

Contreras-Ruiz

García-Posadas

et al. 2015

Journal of Ocular Pharmacology and Therapeutics

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“…Keratoconus (KC), by definition, is a progressive disorder characterized by non-inflammatory corneal ectasia, stromal thinning that leads to corneal surface distortion [64,65]. The etiology of this disease remains unknown, although there is evidence base is genetic and can bond with systemic diseases and obvious factors like excessive rubbing of the eyes, and wearing contact lenses [64,65].…”

Section: Keratoconusmentioning

confidence: 99%

Analysis of the Pathogenic Factors and Management of Dry Eye in Ocular Surface Disorders

Nebbioso¹,

Regno²,

Gharbiya³

et al. 2017

Preprint

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The alteration of the delicate balance that regulates the secretion and distribution of the tear film determines the dry eye (DE) syndrome, because the tear film represents the interface between the eye and the environment. Despite having a multifactorial origin, the main risk factors for the emergence of the ocular disease are female gender and advanced age. Peer-reviewed version available at Int. J. Mol. Sci. 2017, 18, 1764 doi:10.3390/ijms18081764 2 Likewise, morphological changes in several glands and in chemical composition of their secretions such as proteins, mucins, lipidics, aqueous tears, and salinity, are highly relevant factors to maintain a condition of good health of the ocular anterior segment. Another key factor of recurrence and onset of the disease is the presence of local and/or systemic infiammation that reflex on the ocular surface. However, it is one of the most commonly encountered disease in clinical practice and many other causes related to daily life and to lengthen the average life will contribute to the beginning. This review will consider how and what disorders of the ocular surface are responsible for a widespread pathology so. In the end, the most appropriate and new therapies will be briefly exposed according to the specific pathology.

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“…This study of 26 patients with progressive keratoconus showed statistically significant increases in IC grading (superior and temporal; p = 0.005 and p = 0.006, respectively) at 3 months post-treatment versus pretreatment. However, it should be noted that both studies [57,58] are preliminary and comprise small patient numbers, therefore further studies are necessary to confirm these findings.…”

Section: Dry Eye Disease and Other Ocular Conditions Keratoconusmentioning

confidence: 96%

“…Although commonly described as noninflammatory, some studies have reported impaired tear secretion and DED in keratoconus patients [55,56]. Subsequently, a pilot study by Carracedo et al [57] investigated keratoconus patients (n = 15) for the presence of DED, using morphological assessment of goblet cells by IC. They found that, when compared with healthy controls (n = 16), keratoconus patients demonstrated significantly lower densities of goblet cells (p < 0.05), once more showing how IC may be reliably used to assist in confirming DED diagnoses.…”

Section: Dry Eye Disease and Other Ocular Conditions Keratoconusmentioning

confidence: 99%

Biomarkers of Ocular Surface Disease Using Impression Cytology

Hagan

2017

Biomark. Med.

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Impression cytology (IC) is a technique which permits the retrieval of the outermost layer of ocular surface cells via the use of various types of filters. It is a minimally invasive method of evaluating human conjunctival epithelial cell morphology in the diagnosis of dry eye disease, a common and distressing disorder associated with ageing, contact lens wear, autoimmune disorders and refractive (LASIK) surgery. IC may also be utilized in the diagnosis of other ocular diseases, such as keratoconus and thyroid orbitopathy. More recently, IC has been utilized for the subsequent investigation of gene and protein expression of conjunctival cells in order to identify novel diagnostic biomarkers and to further our understanding of the mechanisms underlying ocular surface disease. This review will therefore examine the literature concerning the role of IC in identifying cellular markers of eye disease, systemic diseases with ocular involvement and potential novel therapeutic targets. Impression cytology (IC) is a minimally invasive method of evaluating human ocular surface cells and is considered as the 'gold standard' technique for assessing cell morphology. Introduced by Thatcher et al. [1] and Egbert et al. [2], IC is an easy-to-use technique of directly retrieving (mainly conjunctival) cells, using various filter types which are gently applied to exposed (interpalpebral) conjunctival surfaces. The filters used include cellulose acetate [3], polycarbonate (Biopore, Millipore UK Ltd, Watford, UK) [4], nitrocellulose [5] or polyethersulfone (PES) [6] which are gently applied to exposed (interpalpebral) conjunctival surfaces. Recently, a more standardized tool for IC sampling has been introduced (Figures 1 & 2). The Eyeprim is a new single-use PES filter sampling medical device for retrieval of conjunctival cells (Opia Technologies, France) and a recent study by Lopez-Miguel et al. [7] performed an analysis of this tool versus the traditional IC method (PES). On a cohort of 20 healthy individuals, they extracted and compared RNA from both devices and found no significant differences in the mean yield (p ≥ 0.45), the total RNA amount (μg), or the amount normalized to membrane area [7]. Although an earlier study of the Eyeprim [8], suggested that it recovered more cells than traditional IC, Lopez-Miguel et al. [7] did not observe differences in the RNA collected between this device and PES.Historically, IC has been used to analyze pathological changes to conjunctival cells for indicators of squamous metaplasia in ocular surface disease (OSD) [9]. More recently, however, researchers have used IC to examine specific markers of inflammation, for example, HLA-DR, ICAM-1 and CD8 [10][11][12], and to examine novel biomarkers of dry eye disease (DED). The latter is performed in an attempt to understand the mechanisms underpinning DED pathophysiology and is now feasible, due to vast improvements in the assay sensitivities for gene and protein examination [13]. As a result, IC membranes can be subsequently analyzed using techniq...

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Signs and Symptoms of Dry Eye in Keratoconus Patients: A Pilot Study

Abstract: The parameters evaluated in this study indicate that KC patients suffer greater symptoms of dry eye and greater tear instability, primarily due to the decreased mucin production in their tears, than do healthy patients with no KC.

Cited by 57 publications

References 42 publications

Inflammatory Cytokine-Mediated Regulation of Thrombospondin-1 and CD36 in Conjunctival Cells

Inflammatory Cytokine-Mediated Regulation of Thrombospondin-1 and CD36 in Conjunctival Cells

Analysis of the Pathogenic Factors and Management of Dry Eye in Ocular Surface Disorders

Biomarkers of Ocular Surface Disease Using Impression Cytology

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