Treatment and diagnosis of ocular surface disorders

Abstract

The present invention provides an ophthalmic formulation consisting essentially of one or more pharmaceutically acceptable excipients; a pharmaceutically active compound that is capable of reducing the amount of inflammatory neutrophil product on the ocular surface; and optionally a second pharmaceutically active compound selected from the group consisting of a steroid, an anti-inflammatory agent, a mucolytic agent and a combination thereof. In particular, the present invention provides an ophthalmic formulation where the pharmaceutically active compound is capable of treating a clinical condition selected from the group consisting of inflammatory and immunological ocular surface disease that can cause symptoms of ocular discomfort, mucocellular aggregates/debris in tear film, symblepheron formation, fornix foreshortening, eyelid margin/conjunctival keratinization, corneal neovascularization/pannus, subconjunctival fibrosis, and herpetic eye disease. The present invention also provides a method for diagnosing or monitoring an ocular surface disease.

What is claimed is: 
     
         1 . An ophthalmic formulation consisting of:
 (a) one or more pharmaceutically acceptable ophthalmic excipients;   (b) heparin; and   (c) a second pharmaceutically active compound selected from the group consisting of a steroid, an anti-inflammatory agent, a mucolytic agent and a combination thereof.   
     
     
         2 . The ophthalmic formulation of  claim 1 , wherein said heparin is selected from the group consisting of a coagulant heparin, a non-coagulant heparin, a heparin oligosaccharide, and a combination thereof. 
     
     
         3 . The ophthalmic formulation of  claim 2 , wherein said coagulant heparin is selected from the group consisting of unfractionated heparin, a low molecular weight heparin, an ultra-low molecular weight heparin, and a combination thereof. 
     
     
         4 . The ophthalmic formulation of  claim 2 , wherein said non-coagulant heparin is selected from the group consisting of a sulfation modified heparin, a glycol-split heparin, glycol-split N-acetylated heparin, other heparin derivative, or a combination thereof. 
     
     
         5 . The ophthalmic formulation of  claim 4 , wherein said other heparin derivative is an N-acetylated heparin or negatively charged nanoparticle mimic of heparin. 
     
     
         6 . The ophthalmic formulation of  claim 1 , wherein said second pharmaceutically active compound is selected from the group consisting of methylprednisone, prednisone, dexamethasone, loteprednol etabonate, fluocinolone, difluprednate, fluorometholone, medrysone, fluocinolone, rimexolone triamcinolone, cyclosporine, Lifitegrast®, tacrolimus, interleukin 1 receptor antagonist (anakinra). 
     
     
         7 . The ophthalmic formulation of  claim 1 , wherein said anti-inflammatory agent is non-steroidal anti-inflammatory drug (NSAID). 
     
     
         8 . The ophthalmic formulation of  claim 7 , wherein said NSAID is selected from the group consisting of ketorolac, diclofenac, flurbiprofen, bromfenac, nepafenac, N-acetylcysteine, N-acetylcysteine, Nacystelyn, Dextran, DNaseI (dornase alpha), gelsolin, thymosinβ4, erythromycin, non-antimicrobial derivative of erythromycin, clarithromycin, roxithromycin, Fidaxomicin, Telithromycin, azithromycin, and a combination thereof. 
     
     
         9 . The ophthalmic formulation of  claim 1 , wherein the amount of heparin present in said ophthalmic formulation ranges from about 10 IU/mL to about 1000 IU/mL. 
     
     
         10 . A method of treating an allergic keratoconjunctivitis, viral keratitis, or fungal keratitis, said method comprising administering directly to an outer ocular surface of a patient in need of such a treatment an ophthalmic formulation consisting of a therapeutically effective amount of heparin. 
     
     
         11 . The method of  claim 10 , wherein the amount of heparin present in said ophthalmic formulation ranges from about 10 IU/mL to about 1000 IU/mL. 
     
     
         12 . The method of  claim 10 , wherein said heparin is selected from the group consisting of a coagulant heparin, a non-coagulant heparin, a heparin oligosaccharide, and a combination thereof. 
     
     
         13 . The method of  claim 12 , wherein said coagulant heparin is selected from the group consisting of unfractionated heparin, a low molecular weight heparin, an ultra-low molecular weight heparin, and a combination thereof. 
     
     
         14 . The method of  claim 12 , wherein said non-coagulant heparin is selected from the group consisting of a sulfation modified heparin, a glycol-split heparin, glycol-split N-acetylated heparin, other heparin derivative, or a combination thereof 
     
     
         15 . The method of  claim 14 , wherein said other heparin derivative is an N-acetylated heparin or negatively charged nanoparticle mimic of heparin. 
     
     
         16 . A method of treating an allergic keratoconjunctivitis, viral keratitis, or fungal keratitis, said method comprising administering directly to an outer ocular surface of a patient in need of such a treatment an ophthalmic formulation consisting of a therapeutically effective amount of heparin and a second pharmaceutically active compound selected from the group consisting of a steroid, an anti-inflammatory agent, a mucolytic agent and a combination thereof. 
     
     
         17 . The method of  claim 16 , wherein said second pharmaceutically active compound is selected from the group consisting of methylprednisone, prednisone, dexamethasone, loteprednol etabonate, fluocinolone, difluprednate, fluorometholone, medrysone, fluocinolone, rimexolone triamcinolone, cyclosporine, Lifitegrast®, tacrolimus, interleukin 1 receptor antagonist (anakinra). 
     
     
         18 . The method of  claim 16 , wherein said anti-inflammatory agent is non-steroidal anti-inflammatory drug (NSAID). 
     
     
         19 . The method of  claim 18 , wherein said NSAID is selected from the group consisting of ketorolac, diclofenac, flurbiprofen, bromfenac, nepafenac, N-acetylcysteine, N-acetylcysteine, Nacystelyn, Dextran, DNaseI (dornase alpha), gelsolin, thymosinβ4, erythromycin, non-antimicrobial derivative of erythromycin, clarithromycin, roxithromycin, Fidaxomicin, Telithromycin, azithromycin, and a combination thereof. 
     
     
         20 . The method of  claim 16 , wherein the amount of heparin in said ophthalmic formulation is about 10 IU/mL to about 1000 IU/mL.