Biomarkers for Diagnosis and Prognosis of Corneal Ectatic Disorders

Abstract

The invention relates to the field of the diagnosis and prognosis methods of molecular pathologies. In particular, the invention relates to methods for determining the diagnosis of an ectatic disease of the cornea in a subject, for determining the risk of developing an ectatic disease of the cornea in a subject, for determining the clinical outcome of a subject suffering from an ectatic disease of the cornea and for selecting a subject to be treated with a therapy for an ectatic disease of the cornea based on the determination of the expression levels of TLR2 and/or TLR4 markers. The invention also relates to the use of the TLR2 and/or TLR4 as diagnosis and prognosis markers for an ectatic disease of the cornea.

1 - 31 . (canceled) 
     
     
         32 . An in vitro method for diagnosing an ectatic disease of the cornea in a subject, or for determining the risk of developing an ectatic disease of the cornea in a subject, or for determining the clinical outcome of a subject suffering from an ectatic disease of the cornea or for selecting a subject to be treated with a therapy for an ectatic disease of the cornea which comprises:
 a) determining the expression level of TLR2 and/or TLR4 in a sample from said subject; and   b) comparing said expression level with a reference value   
       wherein, if the expression level of TLR2 and/or TLR4 is higher than said reference value is indicative that the subject suffers from an ectatic disease of the cornea or that the subject has high risk of developing an ectatic disease of the cornea or that the subject has a negative clinical outcome or that the subject is candidate to be treated with a therapy for an ectatic disease of the cornea. 
     
     
         33 . The in vitro method according to  claim 32  wherein said ectatic disease of the cornea is selected from subclinical keratoconus, clinical keratoconus, pellucid marginal degeneration, keratoglobus and ectasia post refractive corneal surgery. 
     
     
         34 . The in vitro method according to  claim 33 , wherein said ectatic disease of the cornea is subclinical keratoconus, in which case the reference value corresponds to the expression levels of TLR2 and/or TLR4 measured in a sample from a healthy subject. 
     
     
         35 . The in vitro method according to  claim 33 , wherein said ectatic disease of the cornea is clinical keratoconus, in which case the reference value corresponds to the expression levels of TLR2 and/or TLR4 measured in a sample from a subject suffering from subclinical keratoconus. 
     
     
         36 . The in vitro method according to  claim 33 , wherein said ectatic disease of the cornea is pellucid marginal degeneration, in which case the reference value corresponds to the expression levels of TLR2 and/or TLR4 measured in a sample from a healthy subject. 
     
     
         37 . The in vitro method according to  claim 32 , wherein the sample from said subject is selected from conjunctival and corneal tissue. 
     
     
         38 . The in vitro method according to  claim 32 , wherein said expression level comprises determining the level of mRNA encoded from the TLR2 and/or TLR4 gene or determining the level of the TLR2 and/or TLR4 protein. 
     
     
         39 . The in vitro method according to  claim 38 , wherein the protein level is determined by a method selected from immunohistochemistry, Western blot, flow cytometry or by ELISA. 
     
     
         40 . The in vitro method for diagnosing an ectatic disease of the cornea in a subject according to  claim 32  which also comprises determining at least one parameter selected from: diopters, corneal thickness and corneal elevation. 
     
     
         41 . The in vitro method for determining the risk of developing an ectatic disease of the cornea in a subject according to  claim 32 , wherein the subject has been previously diagnosed as having a refractive defect. 
     
     
         42 . The in vitro method for determining the risk of developing an ectatic disease of the cornea in a subject according to  claim 32 , wherein said subject has developed a previous ocular pathology selected from: ocular itching, eye rubbing, biomicroscopic signs and conjunctival hyperemia. 
     
     
         43 . The in vitro method for selecting a subject to be treated with a therapy for an ectatic disease of the cornea according to  claim 32 , wherein said therapy is selected from corneal crosslinking, intracorneal rings and refractive surgery. 
     
     
         44 . An in vitro method for determining whether a subject suffering from a refractive defect is a candidate for a refractive surgery therapy or for determining the risk that a subject suffers ectasia following refractive surgery which comprises:
 a) determining the expression level of TLR2 and/or TLR4 in a sample from said subject; and   b) comparing said expression level with a reference value   
       wherein if the expression level of TLR2 and/or TLR4 is higher than said reference value is indicative that said subject is not candidate to be treated with a refractive surgery for said refractive defect or is indicative that said subject shows high risk of suffering ectasia following refractive surgery. 
     
     
         45 . A composition or kit for diagnosis of an ectatic disease of the cornea which comprises an antibody, a polypeptide, a primer and/or a probe which specifically bonds to TLR2 and/or TLR4. 
     
     
         46 . A method for determining the diagnosis of an ectatic disease of the cornea in a subject, for determining the risk of developing an ectatic disease of the cornea in a subject, for determining the clinical outcome of a subject suffering from an ectatic disease of the cornea or for selecting a subject to be treated with a therapy for an ectatic disease of the cornea comprising the use of the composition or kit according to  claim 45 . 
     
     
         47 . The in vitro method according to  claim 44 , wherein the sample from said subject is selected from conjunctival and corneal tissue. 
     
     
         48 . The in vitro method according to  claim 44 , wherein said expression level comprises determining the level of mRNA encoded from the TLR2 and/or TLR4 gene or determining the level of the TLR2 and/or TLR4 protein. 
     
     
         49 . The in vitro method according to  claim 48  wherein the protein level is determined by a method selected from immunohistochemistry, Western blot, flow cytometry or by ELISA.