Anti-inflammatory and mydriatic intracameral solutions for inhibition of postoperative ocular inflammatory conditions

Abstract

The present invention provides methods for inhibiting postoperative inflammatory conditions following ophthalmologic surgical procedures by administering intraocularly during an ophthalmologic surgical procedure a solution including a nonsteroidal anti-inflammatory agent and an alpha-1 adrenergic mydriatic agent, such as a liquid irrigation solution of ketorolac and phenylephrine.

1 . A method for inhibiting a postoperative inflammatory condition following an ophthalmologic surgical procedure comprising:
 identifying a subject with an elevated risk of suffering from a postoperative inflammatory condition;   administering intraocularly to the subject during an ophthalmologic surgical procedure a solution including a nonsteroidal anti-inflammatory drug (NSAID) and an alpha-1 adrenergic receptor agonist mydriatic agent in an intraocular irrigation carrier, wherein the NSAID and the mydriatic agent are included in the solution in amounts sufficient to maintain intraoperative pupil diameter by promoting mydriasis and inhibiting miosis, and a sufficient amount of the solution is administered for uptake of an amount of the NSAID in ocular tissues sufficient for inhibition of cyclooxygenases for a period of at least six hours postoperatively, thereby inhibiting the postoperative inflammatory condition.   
     
     
         2 . The method of  claim 1 , wherein the NSAID is selected from the group consisting of flurbiprofen, suprofen, diclofenac, ketoprofen, ketorolac, indomethacin, nepafenac and bromfenac. 
     
     
         3 . The method of  claim 1 , wherein the alpha-1 adrenergic receptor agonist is selected from the group consisting of phenylephrine, epinephrine, oxymetazoline and naphazoline. 
     
     
         4 . The method of  claim 1 , where in the NSAID is ketorolac and the mydriatic agent is phenylephrine. 
     
     
         5 . The method of  claim 4 , wherein the solution comprises phenylephrine at a concentration of from 240 to 720 μM and the ketorolac is present at a concentration of from 44 to 134 μM. 
     
     
         6 . The method of  claim 1 , wherein the subject is identified prior to the procedure as having an elevated risk of suffering from a postoperative inflammatory condition. 
     
     
         7 . The method of  claim 1 , wherein the subject is identified during the procedure as having an elevated risk of suffering from a postoperative inflammatory condition. 
     
     
         8 . The method of  claim 1 , wherein a sufficient amount of the NSAID and the mydriatic agent are included in the solution to maintain an intraoperative pupil diameter of at least 6.0 mm during the procedure. 
     
     
         9 . The method of  claim 1 , wherein the solution results in at least 90% inhibition of baseline cyclooxygenase-1 and cyclooxygenase-2 activity levels in ocular tissues for a period of at least six hours postoperatively. 
     
     
         10 . The method of  claim 1 , wherein the solution results in at least 90% inhibition of baseline cyclooxygenase-1 and cyclooxygenase-2 activity levels in ocular tissues for a period of at least eight hours postoperatively. 
     
     
         11 . The method of  claim 1 , wherein the solution results in at least 85% inhibition of baseline cyclooxygenase-1 and cyclooxygenase-2 activity levels in ocular tissues for a period of at least ten hours postoperatively. 
     
     
         12 . The method of  claim 1 , wherein the postoperative inflammatory condition is selected from the group consisting of toxic anterior-segment syndrome, cystoid macular edema, acute endophthalmitis, posterior capsule opacification, anterior capsule contraction, herpes simplex virus keratitis after cataract surgery, postsurgical hypotony, nylon suture toxicity, long-term corneal endothelial cell loss after cataract surgery, corneal edema, iris chafing, corneo-retinal inflammatory syndrome, scleritis, episcleritis, vitreous wick syndrome, post-operational acute iridocyclitis, uveitis, epiretinal deposits after cataract extraction, reiterative membranous proliferation with giant-cell deposits, toxic vitreitis, posterior synechia, postoperative intraocular fibrin formation, incisional fibrosis, complications of macular hole surgery, choroidal effusion, and hypopyon. 
     
     
         13 . The method of  claim 1 , wherein the subject is at elevated risk of a postoperative inflammatory condition because of a preoperative physiologic condition or characteristic, a preoperative treatment history, surgical trauma, or the surgical placement of a device that is associated with an enhanced incidence of postoperative inflammation. 
     
     
         14 . The method of  claim 13 , wherein the subject is at elevated risk of a postoperative inflammatory condition because of a preoperative physiologic condition or characteristic including a preoperative dilated pupil diameter of less than 6 mm, floppy iris syndrome, uveitis, retinal vein occlusion, epiretinal membrane, being over 65 years of age, diabetes mellitus, diabetic macular edema, diabetic retinopathy, macular degeneration, or systemic hypertension; a preoperative treatment history including previous ocular surgery or pharmacologic treatment with an alpha-1 adrenergic receptor antagonist or latanoprost; surgical trauma including posterior capsule rupture, secondary capsulotomy, iris incarceration, retained lens material, or vitreous loss; and the surgical placement of nylon sutures, iris-fixated intraocular lens or an anterior chamber intraocular lens. 
     
     
         15 . The method of  claim 1 , wherein the solution is administered by continuous intraocular irrigation during the procedure. 
     
     
         16 . The method of  claim 15 , wherein the solution is administered by continuous intraocular irrigation during the procedure followed by injection of a bolus of the solution at the end of the procedure. 
     
     
         17 . The method of  claim 1 , wherein the solution is administered by intraocular injection during a procedure in which another therapeutic agent is injected intraocularly. 
     
     
         18 . The method of  claim 1 , wherein the solution is administered by intraocular injection preoperatively, intraoperatively and/or postoperatively. 
     
     
         19 . A method for inhibiting a postoperative inflammatory condition following an ophthalmologic surgical procedure comprising:
 identifying a subject with an elevated risk of suffering from a postoperative inflammatory condition;   administering intraocularly to the subject during an ophthalmologic surgical procedure a solution including a nonsteroidal anti-inflammatory drug (NSAID) and an alpha-1 adrenergic receptor agonist mydriatic agent in an intraocular irrigation carrier, wherein the NSAID and the mydriatic agent are included in the solution in amounts sufficient for maintenance of intraoperative pupil diameter and inhibition of the postoperative inflammatory condition.   
     
     
         20 . A method for inhibiting a postoperative inflammatory condition following an ophthalmologic surgical procedure comprising intraocular administration during an ophthalmologic surgical procedure, to a subject at risk of a postoperative inflammatory condition, a solution including a nonsteroidal anti-inflammatory drug (NSAID) and an alpha-1 adrenergic receptor agonist mydriatic agent in an intraocular irrigation carrier, wherein the NSAID and the mydriatic agent are included in the solution in amounts sufficient to maintain intraoperative pupil diameter by promoting mydriasis and inhibiting miosis, and a sufficient amount of the solution is administered for uptake of an amount of the NSAID in ocular tissues sufficient for inhibition of cyclooxygenases for a period of at least six hours postoperatively, thereby inhibiting the postoperative inflammatory condition. 
     
     
         21 . A method for reducing the incidence or severity of cystoid macular edema following an ophthalmologic surgical procedure comprising:
 identifying a subject with an elevated risk of suffering from cystoid macular edema;   administering intraocularly to the subject during an ophthalmologic surgical procedure a solution including a nonsteroidal anti-inflammatory drug (NSAID) and an alpha-1 adrenergic receptor agonist mydriatic agent in an intraocular irrigation carrier, wherein the NSAID and the mydriatic agent are included in the solution in amounts sufficient for maintenance of intraoperative pupil diameter and reduction of the incidence or severity of postoperative cystoid macular edema.