"Male Predominance and Pubertal Resolution in Vernal Keratoconjunctivitis: Exploring Associations with Ocular Surface Sex Steroid Intracrinology".

AIM: To evaluate the role of sex steroid hormones in influencing the sex- and age-related predilection of vernal Keratoconjunctivitis (VKC). METHODS: Prospective case-control study of 84 VKC patients ,stratified by sex and age (≤16/>16 years) and 96 age and sex-matched controls .Conjunctival imprint cytology and peripheral blood samples were collected during active and quiet disease stages. Gene expression of sex steroid-metabolizing enzymes (CYP19A1, STS, SRD5A2, UGT2B), estrogen and progesterone receptors (ESR1, ESR2, NR3C3) was quantified by qPCR. Plasma DHEA-S, estradiol, testosterone, and progesterone levels were measured by ELISA in a subset. RESULTS: Conjunctival NR3C3 gene expression and the Estrogen receptor (ESR1/ESR2) were upregulated in all VKC cases compared to control irrespective of age; sex and disease activity. During active disease, CYP19A1, SRD5A2 and UGT2B expression were higher than in the quiet stage . Age-stratified analysis showed upregulation of SRD5A2, STS, UGT2B and ESR2 in age >16 years, whereas age ≤16 years and males exhibited downregulation of SRD5A2, STS, and UGT2B with persistent CYP19A1 upregulation. Females showed higher UGT2B expression. Multiple linear regression analysis revealed age and disease activity as significant contributors to gene expression in VKC (p=0.007; p=0.01 respectively). Plasma DHEA-S was significantly reduced in VKC patients with quiet disease and in males ≤16years. CONCLUSION: Altered ocular surface intracrinology with enhanced local estrogenic signaling, particularly in males and pre-pubertal individuals may be associated with the sex and age-related predilection of vernal keratoconjunctivitis.