Abstract
Purpose :
Ocular surface (OS) involvement of Stevens-Johnson syndrome(SJS) ranges from lid margin keratinisation to end stage keratopathy with vision loss. Since, SJS is immune mediated, we studied cellular and soluble immune factors at OS of SJS patients.
Methods :
20 SJS patients (n=40 eyes) and 15 healthy controls (n=30 eyes) were studied with prior informed consent and ethics committee approval. Patients underwent vision testing, eversion of lids for keratinisation, Schirmers test, TBUT and ocular surface staining. Severity and extent of OS involvement was graded based on published guidelines and subjects on topical steroids and immunomodulation were excluded. OS immune cells collected in saline wash were stained with antibodies for leukocytes(CD45), T cells(CD3), neutrophils(CD66b), macrophages(CD163), Natural Killer cells(CD56), NKT cells(CD3+ CD56+) and gamma delta T cells(gdT), and analysed by flow cytometry. Percentage of each cell type within CD45+ cells was determined. Soluble tear factors(30) from Schirmer’s strips were measured by multiplex ELISA.
Results :
Total neutrophils, its activated forms were significantly (p<0.05) elevated in SJS compared to controls, while quiescent neutrophils, T cells and NK cells were significantly lower. Leukocytes and gdT cells were elevated but not significant while macrophages, NKT cells and neutrophil-to-T cell ratio remained unaltered between groups. Further, neutrophils were higher in SJS patients with dry eye (DE) and increased grades of hyperemia (p<0.05). Decreased T cells, NKT cells, NK cells and macrophages were observed in SJS patients with higher grades of hyperemia. Tear profiling revealed significant increase in factors related to neutrophil recruitment and activation - IL-8, IL-18, MPO, NGAL and FasL in SJS. Significantly raised Th1 (TNFa, IL-2, IL-6, IFNg) and reduced Th2 cytokines (IL-4, IL-13), with no difference in Th17 (IL17A/F, IL-23) was observed. IL-10 and IP10 were significantly reduced with no change in TGFb.
Conclusions :
Increased neutrophil trafficking, their activation products and inflammatory cytokines on the OS are associated with DE, hyperemia and keratinization in SJS. Our data supports the need for prospective evaluation of neutrophils and associated secretory factors in SJS, which may be targeted using specific immunotherapies.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.