ObjectivesTo detect the serum level of thyroid hormones, vitamin D and vitamin D receptors (VDR) polymorphism in keratoconus (KC) patients and to identify the association between vitamin D deficiency and thyroid dysfunction in KC.MethodsThis cross sectional study included 177 KC patients with no thyroid disorders compared to 85 healthy controls with normal corneal tomography. Measurements of thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free tetraiodothyronine (FT4) and serum 25-OH vitamin D were done using Enzyme linked immusoassay (ELISA test). VDR polymorphisms were tested including [Taq I (rs731236), Apa I (rs7975232) and Bsm I (rs1544410)] using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsAn increase in frequency of thyroid disorders (P= 0.04), decrease in serum 25(OH) vitamin D level (P< 0.001), Taq 1 and tt genotype (P< 0.001) were significantly distributed in KC patients. A significantly higher serum 25(OH) vitamin D level was reported in TT genotype, while insufficient level was more common in Tt genotype (P< 0.001). A deficient serum 25(OH) vitamin D level was predominant in tt genotype (P< 0.001). A 95% confidence interval was in TSH (1.603, 2.946), FT4 (24.145, 77.06), hypothyroidism (1.062, 67.63), insufficient (2.936, 11.643) and deficient vitamin D (5.283, 28.704) and all were significant risk factors for KC with (P< 0.05).ConclusionsBoth thyroid disorders and low vitamin D are potential factors for KC development. Studying VDR at the molecular level provides interesting avenues for future research toward the identification of new KC cases.