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Purpose: 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., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)