OPHTHALMOLOGIC IRRIGATION SOLUTIONS AND METHOD
Solutions for perioperative intraocular application by continuous irrigation during ophthalmologic procedures are provided. These solutions include multiple agents that act to inhibit inflammation, inhibit pain, effect mydriasis (dilation of the pupil), and/or decrease intraocular pressure, wherein the multiple agents are selected to target multiple molecular targets to achieve multiple differing physiologic functions, and are included in dilute concentrations in a balanced salt solution carrier.
1 . A method for perioperatively inhibiting ocular inflammation and maintaining mydriasis during an intraocular ophthalmologic procedure, comprising irrigating intraocular tissues during an intraocular ophthalmologic procedure with a solution including at least an anti-inflammatory agent and a mydriatic agent in a liquid irrigation carrier, wherein the anti-inflammatory agent comprises a non-steroidal anti-inflammatory drug (NSAID) and the mydriatic agent comprises an alpha-1 adrenergic receptor agonist and each of the agents is included in a therapeutically effective amount for the inhibition of inflammation and maintenance of mydriasis when delivered intraocularly during the intraocular ophthalmologic procedure.
2 . The method of claim 1 , wherein the NSAID is included in the solution at a concentration of no more than 100,000 nanomolar and the alpha-1 adrenergic receptor agonist is included in the solution at a concentration of no more than 500,000 nanomolar
3 . The method of claim 1 , wherein the NSAID is selected from the group consisting of flurbiprofen, suprofen, diclofenac, ketoprofen and ketorolac.
4 . The method of claim 3 , wherein the solution further comprises an analgesic agent selected from the group consisting of local anesthetics and opioids.
5 . The method of claim 4 , wherein: the local anesthetic, if selected, is selected from the group consisting of lidocaine, tetracaine, bupivacaine, and proparacaine; and the opioid, if selected, is selected from the group consisting of morphine, fentanyl and hydromorphone.
6 . The method of claim 1 , wherein: the alpha-1 adrenergic receptor agonist is selected from the group consisting of phenylephrine, epinephrine, and oxymetazoline.
7 . The method of claim 1 , wherein the solution further comprises an agent for decreasing intraocular pressure (“IOP reducing agent”) selected from the group consisting of beta adrenergic receptor antagonists, carbonic anhydrase inhibitors, alpha-2 adrenergic receptor agonists, and prostaglandin agonists.
8 . The method of claim 1 , wherein: the beta adrenergic receptor antagonist, if selected, is selected from the group consisting of timolol, metipranolol and levobunolol; the carbonic anhydrase inhibitor, if selected, is selected from the group consisting of brinzolamide and dorzolamide; the alpha-2 adrenergic receptor agonist, if selected, is selected from the group consisting of apraclonidine, brimonidine and oxymetazoline; and the prostaglandin agonist, if selected, is selected from the group consisting of latanoprost, travoprost and bimatoprost.
9 . The method of claim 1 , wherein the solution is continuously applied to the intraocular tissues during the intraocular procedure.
10 . The method of claim 1 , wherein the liquid irrigation carrier further comprises an adjuvant selected from electrolytes sufficient to provide a physiological balanced salt solution, a cellular energy source, a buffering agent, a free-radical scavenger and mixtures thereof.
11 . The method of claim 10 , wherein: the electrolytes, if selected, comprise from 50 to 500 millimolar sodium ions, from 0.1 to 50 millimolar potassium ions, from 0.1 to 5 millimolar calcium ions, from 0.1 to 5 millimolar magnesium ions, from 50 to 500 millimolar chloride ions, and from 0.1 to 10 millimolar phosphate; the buffer, if selected, comprises bicarbonate at a concentration of from 10 to 50 millimolar; the cellular energy source if selected, is selected from dextrose and glucose and is present at a concentration of from 1 to 25 millimolar; and the free-radical scavenger, if selected, comprises glutathione at a concentration of from 0.05 to 5 millimolar.
12 . The method of claim 1 , wherein the liquid irrigation carrier further comprises electrolytes sufficient to provide a physiological balanced salt solution, a cellular energy source, a buffering agent and a free-radical scavenger.
13 . The method of claim 12 , wherein: the electrolytes comprise from 50 to 500 millimolar sodium ions, from 0.1 to 50 millimolar potassium ions, from 0.1 to 5 millimolar calcium ions, from 0.1 to 5 millimolar magnesium ions, from 50 to 500 millimolar chloride ions, and from 0.1 to 10 millimolar phosphate; the buffer comprises bicarbonate at a concentration of from 10 to 50 millimolar; the cellular energy source is selected from dextrose and glucose and is present at a concentration of from 1 to 25 millimolar; and the free-radical scavenger comprises glutathione at a concentration of from 0.05 to 5 millimolar.
14 . The method of claim 1 , wherein the pH of the irrigation solution is between 5.5 and 8.0.
15 . The method of claim 1 , wherein the solution comprises an NSAID and phenylephrine.
16 . The method of claim 1 , wherein the solution comprises an NSAID and epinephrine.
17 . The method of claim 1 , wherein the solution comprises oxymetazoline and an NSAID.
18 . The method of claim 1 , wherein each of the agents contributes to the maintenance of intraoperative mydriasis by providing for mydriasis or inhibiting miosis.
19 . A method for perioperatively inhibiting ocular inflammation and maintaining mydriasis during an intraocular ophthalmologic procedure, comprising irrigating intraocular tissues during an intraocular ophthalmologic procedure with a solution including at least an anti-inflammatory agent and a mydriatic agent in a liquid irrigation carrier, wherein the anti-inflammatory agent comprises a non-steroidal anti-inflammatory drug (NSAID) and the mydriatic agent is selected from the group consisting of epinephrine and phenylephrine and each of the agents is included in a therapeutically effective amount for the inhibition of inflammation and maintenance of mydriasis when delivered intraocularly during the intraocular ophthalmologic procedure.
20 . The method of claim 19 , wherein each of the agents contributes to the maintenance of intraoperative mydriasis by providing for mydriasis or inhibiting miosis.