ABSTRACT
BACKGROUND: Although the oxidative stress status in atopic skin disease has been reported to be elevated, there are still no studies related to the status of oxidative stress in atopic ocular surface disease. The purpose of this study was to evaluate the ocular surface lipid oxidative stress status and inflammation in atopic keratoconjunctivitis (AKC) patients and normal subjects. METHODS: Twenty eight eyes of 14 patients (9 males, 5 females) with AKC and 18 eyes of 9 age and sex matched (4 males and 5 females) normal healthy controls were examined in this prospective study. The severity of atopic dermatitis (AD) was scored by the SCORing Atopic Dermatitis (SCORAD) index. All subjects underwent Schirmer test, tear film break up time (BUT), fluorescein/Rose Bengal stainings, tear collection, and brush cytology from the upper palpebral conjunctiva. The brush cytology samples were stained with Diff-Quik for differentiation of inflammatory cells and immunohistochemistry (IHC) staining with HEL (hexanoyl-lysine) and 4-HNE (4-hydroxy-2-nonenal) to study lipid oxidation. HEL and cytokine (interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ)) levels were measured by enzyme-linked immunosorbent assay (ELISA) from tear samples of AKC patients and control subjects. Toluidine Blue and IHC staining with HEL, 4-HNE and cluster of differentiation 45 (CD45) were performed on papillary samples of AKC patients. This study was conducted in compliance with the "Declaration of Helsinki." RESULTS: The tear stability and vital staining scores were significantly worse in eyes of AKC patients (p<0.05) compared to the controls. Inflammatory cells and positively stained conjunctival epithelial cells for HEL and 4-HNE showed a significant elevation in brush cytology samples of AKC patients. Significantly higher levels of HEL and cytokines were detected in tears of AKC patients compared to controls. Papillary specimens also revealed many CD45 inflammatory cells as well as many cells positively stained with HEL and 4-HNE in IHC. A strong significant linear positive correlation between conjunctival inflammation and epithelial lipid oxidative stress status was observed. Conjunctival lipid oxidative stress also correlated strongly with tear HEL levels and epithelial damage scores. CONCLUSIONS: The ocular surface disease in AKC was characterized by marked tear instability, ocular surface epithelial damage, increase in inflammatory infiltrates and presence of increased lipid oxidation.
Subject(s)
Conjunctivitis, Allergic/complications , Conjunctivitis, Allergic/pathology , Inflammation/complications , Inflammation/metabolism , Lipid Metabolism , Oxidative Stress , Adolescent , Adult , Aldehydes/metabolism , Biomarkers/metabolism , Case-Control Studies , Cell Count , Child , Conjunctiva/metabolism , Conjunctiva/pathology , Conjunctivitis, Allergic/metabolism , Conjunctivitis, Allergic/physiopathology , Cytokines/metabolism , Enzyme-Linked Immunosorbent Assay , Eosinophils/cytology , Epithelium, Corneal/metabolism , Epithelium, Corneal/pathology , Female , Humans , Immunohistochemistry , Inflammation/pathology , Lysine/metabolism , Male , Staining and Labeling , Tears/metabolism , Young AdultABSTRACT
PURPOSE: To investigate the effect of grade 3 nasal conjunctivochalasis (NCCh) on the tear film inflammation, ocular surface findings, and tear function findings. DESIGN: Prospective, observational case series. METHODS: Eleven eyes with Yokoi grade 3 NCCh in which the chalatic conjunctiva occluded the punctum and 18 eyes without NCCh but with central or temporal conjunctivochalasis, or both, and 16 eyes of healthy controls were recruited prospectively. Enzyme-linked immunosorbent assay for inflammatory tear cytokines, tear film break-up time (BUT), Schirmer I test measurements, and fluorescein and rose bengal vital stainings and impression cytologic and brush cytologic analysis for real-time reverse-transcriptase polymerase chain reaction analysis of MUC5AC messenger ribonucleic acid (mRNA) expression were performed. RESULTS: Eyes with grade 3 NCCh had significantly delayed tear clearance. All inflammatory cytokines showed higher values in eyes with grade 3 NCCh compared with the eyes without nasal chalasis with a comparably significant elevation in interleukin-1b and tumor necrosis factor alpha levels. The mean rose bengal score in eyes with grade 3 NCCh was significantly higher compared with eyes without nasal chalasis and eyes of controls. The mean goblet cell density was significantly lower in eyes with grade 3 NCCh with downregulation of the relative MUC5AC mRNA expression. CONCLUSIONS: Inflammation plays an important role in the pathogenesis of conjunctivochalasis and is more pronounced in eyes with nasal chalasis. Pooling of inflammatory cytokines in tears of patients with NCCh associated with delayed tear clearance induces distinct adverse effects that affect the ocular surface health.