To systematically review the literature on the treatment of vernal keratoconjunctivitis (VKC) in children and young adults and conduct comparative efficacy analysis on clinical signs and symptoms using network meta-analyses. Methods.We systematically searched the databases PubMed/MEDLINE, EMBASE, Cochrane Central and Web of Science on 21 October 2019 for randomized controlled trials (RCT). Studies considered had patients with VKC < 20 years of age randomized into either intervention (any medical intervention) or comparator (active treatment, placebo treatment or non-treatment control), where pre-defined outcomes (data from ≥2 weeks and as close as possible to 2 months) of symptoms (itching, tearing, photophobia and foreign body sensation) and signs (hyperaemia, punctate keratitis, Horner-Trantas dots and macropapillae) were reported. Risk of bias within studies was evaluated using the Cochrane risk of bias tool. Comparisons were made using network meta-analyses. Results.We identified 39 studies with data on 2046 individuals. Twenty-three studies were eligible for quantitative analyses. None were systemic therapy. Temporal trend analysis showed that an initial focus on topical mast cell stabilizers turned to a focus on calcineurin inhibitors and a more diverse variety of pharmacological strategies. Studies varied in population, treatment duration and quality. The quantitative analysis revealed that efficacy of different therapies differed substantially across important clinical signs and symptoms, but there was a general trend of superior efficacy when using topical corticosteroids with stronger efficacy of the more potent corticosteroids. Conclusion.We provide an overview of RCTs comparing the efficacy of treatments for VKC in children and young adults, which we find differs across symptoms and signs. Overall, we saw a general trend of superior efficacy with topical corticosteroids. However, our findings highlight the need for better studies, consensus on core outcomes and potential for individualized therapy.
Marianne Schou Institute for Experimental Immunology, University of Copenhagen, Denmark A micromethod of chicken mixed lymphocyte culture is described. In order to test the genetic control of the reaction, lymphocytes from the inbred G‐Bl and G‐B2 strains were cultured together with lymphocytes of the MHC identical chickens of a segregating population of (G‐Bl × G‐B2) F2 hybrids. Most of these combinations showed no response, which is in agreement with the major importance of the lymphocyte activating determinants (Lads) being controlled by the B complex (chicken MHC). A few strong reactions of MLC between B identical individuals indicated, however, that chickens in addition may have Lads controlled by genes not closely linked to the B complex.
The F antigens, which are serologically defined Class I gene products of the major histocompatibility complex in chickens (the B complex), were analysed in outbred birds. Private specificities of the F13 antigen from the inbred CC strain were detected in 20 outbred chickens by a haemagglutination technique. In the GVH-inhibition-release test F13 antigens from outbred and inbred chickens were identical.The L antigens, which are the Class I1 antigens of the B complex, were detected with specific anti L13 alloantisera by indirect immunofluorescence. Antisera defining the L13 antigen(s) of the inbred C C line reacted with all F13 positive outbreds. As a test of one-way direct compatibility of the inbred and outbred animals typing F13, graft versus host reactions were performed, injecting blood of F13 positive outbreds into inbred B'3''3 cggs. N o GVH stimulation attributable to MHC determinants was found. In MLR, responder cells from outbred M H C heterozygous chickens, which typed F13/x, were stimulated by inbred F13113 homozygous typing cells, and weak, but significant, reactions were found. Further analysis in the accompanying paper, however, revealed no difference in the lymphocyte activating determinants (Lads) of inbred and outbred birds typing F13 and L13. No individual has yet been found which carries one of these antigens in the absence of the other.List of abbreviations: B = The complex of linked genes constituting the @ 1982 Munksgaard, Copenhagen
MLR phenotypes of outbred and inbred chickens typing B13 of the major histocompatibility complex (MHC) of the chicken were compared. Fl hybrids of outbred and inbred B13 positive chickens were analysed in mixed lymphocyte culture (MLC). The intermediate strength responses of cells from B" heterozygous outbred chickens stimulated by inbred E l 3 homozygous chicken cells were not due to minor variations of B encoded lymphocyte activating determinants (Lads). Nor were Lads encoded by genes unlinked to the B complex responsible for these reactions. In contrast, Fl anti-parental type reactions were observed, and these alone are probably responsible for the intermediate strength reactions so often seen in typing of heterozygous outbreds with homozygous typing cells.
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