Elevation of Conjunctival Epithelial CD45INTCD11b+CD16+CD14−Neutrophils in Ocular Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Williams, Gwyn Samuel; Tomlins, Paul J.; Denniston, Alastair K; Southworth, Harry; Sreekantham, Sreekanth; Curnow, S. John; Rauz, Saaeha

doi:10.1167/iovs.13-11859

Cited by 25 publications

(25 citation statements)

References 37 publications

(43 reference statements)

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“…Our results confirm a solid increase in granulocytes in inflamed eyes, as reported by Williams et al, 22 although CD45 bright cells were significantly reduced. The percentages of monocytes and T lymphocytes were not significantly different between the two groups, although monocytes were most represented in inflamed eyes and T lymphocytes in noninflamed eyes.…”

Section: Figuresupporting

confidence: 93%

Quantifying Ocular Surface Inflammation and Correlating It With Inflammatory Cell Infiltration In Vivo: A Novel Method

Ferrari

Rabiolo

Bignami

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The purpose of this study was to develop a novel, objective, and semiautomated method to quantify conjunctival redness by correlating measured redness with standard clinical redness and symptom scales and inflammatory cell infiltration. METHODS.Eleven outpatients presenting with mild to severe conjunctival hyperemia were included in the study. Clinical examination included patient history; visual analogue score (VAS) for ocular symptoms; 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ 25) for quality of life/vision; photographs of the anterior segment graded for conjunctival hyperemia, using Efron, relative redness of image (RRI), and edge feature (EF) scales; and conjunctival impression cytology analyzed by flow cytometry. Differences between affected and unaffected eyes were evaluated, and correlations among questionnaire scores, ocular hyperemia grading scores, and assessment of biological markers were performed.RESULTS. Visual analogue score (P < 0.0001), Efron scale (P ¼ 0.0003), RRI scores (P ¼ 0.0004), and EF scores (P < 0.0001) and the percentage of granulocytes (defined as cluster of differentiation [CD] 45 dim ; P ¼ 0.0080) were significantly higher in affected eyes. Conversely, the percentage of CD45 bright leukocytes was reduced in affected eyes (P ¼ 0.0054). Both the RRIs and EFs were positively correlated with VAS, Efron scale, percentages of conjunctival granulocytes, and CD45 bright CD3 neg cells, whereas they were negatively correlated with the percentage of CD45 bright CD3 pos cells. Edge feature and RRI were correlated (Spearman r ¼ 0.78, P < 0.0001).CONCLUSIONS. Ocular redness is a cardinal sign driving clinical judgment in highly prevalent ocular disorders; hence, we suggest that our semiautomated and reproducible method may represent a helpful tool in the follow-up of these patients.Keywords: conjunctival hyperemia, grading score, image processing, impression cytology, ocular redness SCOPO. Sviluppare un nuovo metodo quantitativo e semiautomatico per quantificare l'iperemia congiuntivale e correlarla con parametri clinici e biologici.METODI. Undici pazienti ambulatoriali con iperemia congiuntivale da lieve a severa sono stati inclusi nello studio. I pazienti arruolati sono stati valutati al basale e 20 6 8 giorni dopo. L'esame clinico includeva: storia del paziente; questionario Visual Analogue Score (VAS) al fine di valutare la sintomatologia oculare; questionario 25-Item National Eye Institute Visual Function Questionnaire (NEI-VFQ 25) al fine di valutare la qualità della vita e della visione; fotografie del segmento anteriore analizzate con scala di Efron, Relative Redness of Image (RRI) e Edge Feature (EF); citologia ad impressione congiuntivale processata tramite citometria a flusso. Sono state indagate le differenze tra occhi affetti e non-affetti e le correlazioni tra punteggi ottenuti ai questionari, grado di iperemia congiuntivale e parametri biologici.RISULTATI. Le seguenti misure: VAS (P < 0.0001), scala di Efron (P ¼ 0.0003), RRI (P ¼ 0.0004), EF (...

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Section: Figuresupporting

confidence: 93%

Quantifying Ocular Surface Inflammation and Correlating It With Inflammatory Cell Infiltration In Vivo: A Novel Method

Ferrari

Rabiolo

Bignami

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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“…19,20 The distinction between ''acute'' and ''chronic'' ocular complications of SJS/TEN remains blurred; however, some studies have used an arbitrary cut-off of !12 months to define chronicity. 8,21 Although the cutaneous manifestations generally heal without longterm sequelae, severe ocular surface complications may persist long after the systemic condition has subsided. In addition, chronic ocular disease in SJS/TEN tends to be progressive and unpredictable, with poor correlation with the severity of acute ocular complications.…”

Section: Ocular Complications and Categorizationsmentioning

confidence: 99%

“…20,22 Persistent ocular surface inflammation can result in a multitude of long-standing sequelae such as keratoconjunctivitis sicca, ocular surface keratinization, corneal neovascularization, trichiasis/districhiasis, entropion/ectropion, lagophthalmos, extensive subconjunctival fibrosis, and/or symblepharon formation. 18,21,23,24 Sotozono et al reported that the most common chronic ocular manifestations were the loss of the palisades of Vogt (POV) and development of meibomian gland dysfunction. 8 Corneal complications (neovascularization and opacification) are correlated with the worst longterm visual prognosis.…”

Section: Ocular Complications and Categorizationsmentioning

confidence: 99%

“…34 Others have proposed that the innate-immune system plays a significant role in chronic ocular surface diseases. 21 Arafat et al showed elevated levels of matrix metalloproteinases (MMP)-8, MMP-9, and myeloperoxidase (MPO) in the tears of SJS patients with chronic ocular complications. 35 These enzymes are secreted primarily by activated neutrophils on the ocular surface.…”

Section: Chronic Phasementioning

confidence: 99%

“…35 Using ocular surface impression cytology (OSIC), Williams et al demonstrated elevated levels of CD14+ monocytes and CD45 INT CD11b + CD16 + CD14 À neutrophils in the conjunctiva of SJS/TEN patients. 21 Toll-like receptor 3 (TLR-3) has been shown to be contributory to the chronic ocular manifestations of SJS. 36 In addition, Yao et al reported a disproportionate number of mast cells in the conjunctiva of SJS patients that may serve to activate fibroblasts and the release of fibrogenic cytokines leading to progressive subconjunctival scarring.…”

Section: Chronic Phasementioning

confidence: 99%

See 2 more Smart Citations

Chronic Ocular Complications of Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: The Role of Systemic Immunomodulatory Therapy

Chang

Chodosh

Papaliodis

2016

Seminars in Ophthalmology

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Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, but potentially blinding diseases that affect the skin and mucous membranes. Although the cutaneous manifestations tend to be self-limited and resolve without sequelae, the chronic ocular complications associated with SJS/TEN can persist despite local therapy. Poor understanding of the underlying pathophysiology and lack of a standardized clinical approach have resulted in a paucity of data in regards to suitable treatment options. Inflammatory cellular infiltration and elevated levels of ocular surface cytokines in the conjunctival specimens of affected patients give credence to an underlying immunogenic etiology. Furthermore, the presence of ongoing ocular surface inflammation and progressive conjunctival fibrosis in the absence of exogenous aggravating factors suggest a possible role for systemic immunomodulatory therapy (IMT). We review in detail the proposed immunogenesis underlying chronic ocular SJS/TEN and the possible utility of systemic IMT.

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A cross-sectional comparative study on chronic ocular manifestations of Stevens–Johnson syndrome and toxic epidermal necrolysis in Chinese eyes: a 15-year case series

Chow

et al. 2017

Int Ophthalmol

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Elevation of Conjunctival Epithelial CD45^INTCD11b⁺CD16⁺CD14⁻Neutrophils in Ocular Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Cited by 25 publications

References 37 publications

Quantifying Ocular Surface Inflammation and Correlating It With Inflammatory Cell Infiltration In Vivo: A Novel Method

Quantifying Ocular Surface Inflammation and Correlating It With Inflammatory Cell Infiltration In Vivo: A Novel Method

Chronic Ocular Complications of Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: The Role of Systemic Immunomodulatory Therapy

A cross-sectional comparative study on chronic ocular manifestations of Stevens–Johnson syndrome and toxic epidermal necrolysis in Chinese eyes: a 15-year case series

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