Impression Cytology: Recent Advances and Applications in Dry Eye Disease

Lopin, Eli; Deveney, Tatiana; Asbell, Penny A.

doi:10.1016/s1542-0124(12)70301-4

Cited by 62 publications

(43 citation statements)

References 94 publications

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“…HLA-DR molecules are upregulated in response to signaling (reviewed by Lopin et al, 2009) and are a biomarker for immune activation (Newman, 1997). Increased HLA-DR expression has been associated with many immune disorders/inflammatory processes (Jaraquemada et al, 1986; Ichikawa et al, 1990; Ichikawa et al, 1990; Ishihara et al, 1994; Goronzy and Weyand, 1990; Pisella et al, 2000) and ocular surface diseases such as DED (Baudouin et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

“…Since its introduction (Egbert et al , 1977), IC has been found to be useful in assessing the ocular surface in various ocular disorders such as dry eye/keratoconjunctivitis sicca (KCS; Wittpenn et al, 1986; Brignole et al, 2001), cicatricial ocular pemphigoid (Rivas et al, 2004), and vitamin A deficiency (McKelvie, 2003; Natadisastra et al, 1988) and has been used in clinical trials to evaluate HLA-DR expression in ocular surface diseases (Barabino et al, 2010; Mrugacz et al, 2007; Rolando et al, 2005; Baudouin et al, 2002; Brignole et al, 2000; Pisella et al, 2000; Tsubota et al, 1999; Baudouin et al, 1997; Baudouin et al, 1992). However, the reliability, reproducibility and storage limitations for the use of relative HLA-DR expression on IC-collected cells as a biomarker of inflammation for clinical trials has not yet been clearly established although there are several articles highlighting the uses of IC (Barabino et al, 2010; Baudouin et al, 1992; Baudouin et al, 1997; Baudouin et al, 2000; Brignole et al, 1998; Brignole et al, 2000; Brignole et al, 2001; Brignole-Baudouin et al, 2004a; Brignole-Baudouin et al, 2004b; Calonge et al, 2004; Lopin et al, 2009; Fernandez et al, 2001; McKelvie, 2003; Natadisastra et al, 1987; Natadisastra et al, 1988; Nelson et al, 1983; Puangsricharern and Tseng, 1995; Rolando et al, 2005; Roy et al, 2011; Singh et al, 2005; Stern et al, 2002; Stevenson et al, 2000; Thiel et al, 1997; Tole et al, 2001; Tseng, 1985. Tsubota et al, 1999; Wittpenn et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

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HLA-DR expression as a biomarker of inflammation for multicenter clinical trials of ocular surface disease

Epstein

Gadaria-Rathod

Wei

et al. 2013

Experimental Eye Research

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There are currently no validated minimally invasive objective metrics for the classification and evaluation of ocular surface diseases and/or for evaluating treatment efficacy. We thus sought to establish a standardized methodology for determining the relative amount of the inflammatory biomarker HLA-DR on the ocular surface and to evaluate the precision, reliability and repeatability of its use for large multicenter clinical trials and translational research studies of ocular surface disease. Multiple studies were conducted to establish a Standard Operating Procedure (SOP) for utilizing HLA-DR expression as a minimally invasive, objective, ocular surface inflammatory biomarker. The established SOPs provide specific guidelines for HLA-DR collection and analysis, in order to incorporate it reliably into multicenter clinical trials and/or translational research. Duplicate cell samples from impression cytology (IC) samples of both normal and dry eye individuals were collected and split to assess repeatability (between the splits and between the duplicate samples). To determine storage capability, one duplicate was stained immediately and the other after 30 days cold storage. To demonstrate the feasibility of the use of the SOP for a multicenter clinical trial, clinicians out-of-state were trained to collect IC samples, and the samples shipped to our Biomarker Laboratory, logged, processed and analyzed. Demonstration of the ability to incorporate of IC into a randomized double masked clinical trial of dry eye disease (DED) was performed. In all cases, processing and analyses were performed by a masked independent observer. The validity/viability of the SOPs was established by demonstrating that: 1) sufficient numbers of cells can be collected via IC; 2) the precision/ repeatability of the relative biomarker expression quantified in samples; 3) personnel at distant sites can be taught to collect, store and ship samples successfully; 4) samples can be stored for up to 30 days (refrigeration) before processing without affecting results; 5) IC can be incorporated Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Presented in part at the 2010 annual meeting of the Association for Research in Vision and Ophthalmology. into a double blind randomized clinical trial (RCT) of DED; and 6) the Biomarker Laboratory can track a large number of masked samples reliably. In conclusion, our standard operating procedure for impression cytology analysis of HLA-DR expression appears to be repeatable and reproducible for use in multicenter clinical trials, providing a minimally invasive objec...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HLA-DR expression as a biomarker of inflammation for multicenter clinical trials of ocular surface disease

Epstein

Gadaria-Rathod

Wei

et al. 2013

Experimental Eye Research

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“…Impression cytology method, as a simple, non-invasive, practical, and effective method for ocular surface examination [14], can be used for the pathological diagnosis of dry eye. In Fig.…”

Section: Discussionmentioning

confidence: 99%

Effect of lacrimal plugs combined with deproteinized calf blood extract eye gel for filamentary keratitis

Liu

et al. 2010

j ocul biol dis inform

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This study aims to investigate the efficacy of lacrimal plugs combined with deproteinized calf blood extract eye gel on the treatment of dry-eye-associated filamentary keratitis. Lacrimal plugs were inserted into both the upper and lower puncta of 15 patients (28 eyes). Deproteinized calf blood cxtract eye gel was applied in two patients who were not cured after this operation. All patients were asked to complete three questionnaires 1 day before the surgery and at 1 week and 1 month after the surgery. Ophthalmologic examinations were carried out and repeated at 1 day and at 1 week and 1 month after plug insertion, which include fluorescein staining, tear break-up time (BUT), Schirmer test I (STI), corneal confocal microscope (HRT-III), and impression cytology (IC). Symptoms were relieved in all patients 1 month after the application of lacrimal plugs. Deproteinized calf blood extract eye gel was applied to two patients whose symptoms remained after lacrimal plug implantation for 1 week. At 3 weeks later, the symptoms disappeared and cornea fluorescein stain was hardly identified. The lacrimal river in all patients became broader after the surgery, 11 of whom reached 0.3 mm. Cornea filamentary disappeared in all patients. The average of BUT and ST were increased to 7.50 ± 1.897 s (p < 0.001) and 8.12 ± 1.996 mm at 1 week after the operation and 7.94 s and 9.00 ± 1.897 mm at 1 month later, respectively. Photography from HRT-III suggested that the state of corneal epithelium was markedly improved, including the squamous metaplasia of the epithelial layer of the cornea and the bend of nerve fibers under the corneal epithelium. IC also suggested that the squamous metaplasia of epithelial layer of conjunctiva in these patients was improved. The symptoms of patients suffering from severe filamentary keratitis were remarkably relieved by using lacrimal plugs, which could increase the tear volume of the ocular surface, improve the condition of tear film, and promote the recovery of corneal diseases. For patients with more severe symptoms, additional usage of deproteinized calf blood extract eye gel could assist the treatment. Therefore, lacrimal plugs combined with deproteinized calf blood extract eye gel are suggested to be an effective method to treat severe filamentary keratitis.

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“…Impression cytology has led to an increased understanding of the pathophysiology of DED and helped to confirm that inflammation in the ocular surface plays an important role and is clearly associated with the clinical signs of the disease [20]. Impression cytology samples are helpful in analyzing different immune biomarkers of inflammation and may be identified in the tears and conjunctiva of patients with DED.…”

Section: Diagnostic Testsmentioning

confidence: 99%