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Keratoconus is a degenerating disease of the eye which causes an irregularly shaped cornea leading to severe impairment of vision. Tear proteomics in keratoconus has been a topic of substantial discussion and speculation over many years. This study was designed to examine the levels of total protein, lactoferrin, secretory IgA and serum albumin in the tear film of people with keratoconus. Basal tears were collected using a capillary tube and corneal curvature was mapped using a topographer. Total protein in tears was estimated. The amount of regulated protein lactoferrin, constitutive protein sIgA and serum protein albumin was measured using specific ELISAs. The changes in protein concentrations in tears were correlated to the degree of corneal asphericity. There was a two-fold (p<0.0001) decrease in total protein levels between keratoconus (3.86 ± 1.62 mg/ml) and normal (7.00 ± 1.58 mg/ml) tears. The amount of lactoferrin (0.67 ± 0.28 vs. 1.13 ± 0.29 mg/ml) and secretory IgA (0.78 ± 0.36 vs. 1.70 ± 0.66 mg/ml) were significantly (p<0.0001) reduced in keratoconus tears. Variation in serum albumin levels between keratoconus (8.18 ± 4.72 μg/ml) and normal tears (11.66 ± 8.20 μg/ml) were not significant. The differences in total protein, lactoferrin and secretory IgA were not associated with contact lens wear, age, gender or atopy of subjects. The keratometry reading was negatively correlated to tear levels of total protein (r = −0.59, p < 0.01) lactoferrin (r = −0.40, p < 0.05) and secretory IgA (r = −0.34, p < 0.05). The tears of keratoconus subjects appear to have an altered protein profile, and one that might change with the severity of the disease. These findings may lead the way to understanding or monitoring disease progression.★ Tear protein levels are profoundly altered in keratoconus compared to normals. ★ Contact lens wear and atopy did not influence the tear protein changes. ★ Tear protein changes correlated to severity of keratoconus. ★ First study to quantify the tear proteins levels in keratoconus.