Reduction Of Ocular Pain Research Articles

Intracameral phenylephrine and ketorolac during cataract surgery to maintain intraoperative mydriasis and reduce postoperative ocular pain: Integrated results from 2 pivotal phase 3 studies

To evaluate the efficacy and safety of phenylephrine 1.0%-ketorolac 0.3% (Omidria) for maintenance of mydriasis during, and reduction of ocular pain after, cataract surgery. Twenty centers in the United States and the Netherlands. Prospective randomized clinical trials. Patients having cataract surgery or refractive lens exchange were enrolled in 2 clinical trials. Phenylephrine 1.0%-ketorolac 0.3% or placebo was added to irrigation solution and administered intracamerally during the procedure. Integrated analyses of primary and secondary endpoints were conducted. The clinical trials comprised 808 patients (403 treatment and 405 placebo). Phenylephrine 1.0%-ketorolac 0.3% was superior to placebo for the maintenance of mydriasis during, and reduction of ocular pain following, cataract surgery. The mean area under the curve (AUC) change from baseline in pupil diameter was 0.08 mm for treatment compared with -0.50 mm for placebo (P < .0001). The mean AUC of ocular pain visual analog scale scores within 12 hours postoperatively was 4.16 mm for the treatment group and 9.06 mm for the placebo group (P < .001). Results of all secondary efficacy analyses demonstrated a significant treatment effect associated with phenylephrine 1.0%-ketorolac 0.3%. Treatment-emergent adverse events were as expected for a population having cataract surgery; no clinically significant differences in safety measures were observed between treatment groups. In this integrated analysis, phenylephrine 1.0%-ketorolac 0.3% administered intracamerally with irrigation solution during cataract surgery was safe and effective for maintaining mydriasis during the procedure and reducing postoperative ocular pain. Dr. Schaaf is an employee and holds an equity interest in Omeros Corporation. Drs. Hovanesian, Sheppard, Trattler, Gayton, and Ng are consultants to Omeros Corporation. No other author has a financial or proprietary interest in any material or method mentioned.

Bromfenac Ophthalmic Solution 0.07%: A Review of Its Use After Cataract Surgery.

The nonsteroidal anti-inflammatory drug bromfenac has recently been reformulated with a lower pH to facilitate a reduction in the concentration of bromfenac (to 0.07%) while ensuring an ocular bioavailability similar to that of the 0.09% formulation. Bromfenac ophthalmic solution 0.07% (hereafter referred to as bromfenac 0.07%) [Prolensa(®)] is a once-daily topical ophthalmic solution available in the USA and Canada for the treatment of postoperative inflammation and the reduction of ocular pain in patients who have undergone cataract surgery. In an integrated analysis of two multicentre, phase III studies, bromfenac 0.07% was significantly more effective than placebo in reducing ocular inflammation and pain. In these studies, bromfenac 0.07% was well tolerated, with significantly lower incidences of adverse events, and adverse events affecting the study eye than with placebo. The most common adverse events in the study eye (eye pain, anterior chamber inflammation, foreign body sensation, photophobia, conjunctival hyperaemia and corneal oedema) occurred in numerically fewer bromfenac 0.07% than placebo recipients. Thus, current evidence suggests once-daily bromfenac 0.07% extends the treatment options currently available for the management of postoperative inflammation and pain following cataract surgery.

Update on twice-daily bromfenac sodium sesquihydrate to treat postoperative ocular inflammation following cataract extraction

Ophthalmic bromfenac sodium sesquihydrate is a topically applied selective cyclooxygenase (COX)-2 inhibitor. It is similar to amfenac, except for a bromine atom at the C4 of the benzoyl ring position, which markedly affects its in vitro and in vivo potency, extends the duration of anti-inflammatory activity, and enhances its inhibitory effect on COX-2 absorption across the cornea and penetration into ocular tissues. The United States Food and Drug Administration approved bromfenac in 2005 for the treatment of postoperative inflammation and the reduction of ocular pain in patients who have undergone cataract surgery. Nonsteroidal anti-inflammatory drugs (NSAIDs), and among them bromfenac, could be even more effective than steroids at reestablishing the blood–aqueous barrier, as revealed by flare on slit-lamp examination and as quantitatively measured using ocular fluorophotometry. Similar to other NSAIDs, it has a role in inhibiting intraoperative miosis during cataract surgery. However, bromfenac also seems to be useful in other situations, such as refractive surgery, allergic conjunctivitis (not useful in dry eye), choroidal neovascularization, and even ocular oncology. No reports of systemic toxicity have been published and bromfenac has good topical tolerance with a low incidence of adverse effects.

Once daily dosing of bromfenac ophthalmic solution 0.09% for postoperative ocular inflammation and pain

Objective:To evaluate the efficacy and ocular safety of bromfenac ophthalmic solution 0.09% dosed once daily for the treatment of ocular inflammation and pain following cataract extraction with posterior chamber intraocular lens implantation.Methods:A total of 455 subjects (455 study eyes: 230 bromfenac, 225 placebo) were enrolled in two randomized double-masked, placebo-controlled, clinical trials at 64 ophthalmology clinics in the United States. Subjects were randomized to receive either bromfenac 0.09% or placebo dosed once daily. Dosing began 1 day before cataract surgery (Day -1), continued on day of surgery (Day 0), and for 14 days following surgery. Evaluations were completed on Days 1, 3, 8, 15 and 22. The primary efficacy endpoint was cleared summed ocular inflammation score (SOIS) by Day 15. The secondary efficacy endpoint was the number of subjects who were pain-free at Day 1.Results:The bromfenac 0.09% group was significantly higher compared to the placebo group in the primary endpoint of the proportion of subjects who had cleared ocular inflammation by Day 15 (P < 0.0001). The mean SOIS for the bromfenac 0.09% group was lower than the placebo group at Days 3, 8, 15, and 22 (P < 0.0001). More bromfenac 0.09% subjects were pain free at Days 1, 3, 8, and 15 (P < 0.0001). Fewer subjects in the bromfenac 0.09% group withdrew from the clinical trials due to lack of efficacy at Day 15 (P < 0.0001). Fewer adverse events were reported in the bromfenac 0.09% group than the placebo group. Limitations included advanced age, female predominance, and surgical nuances among cataract surgeons, making cross-trial comparisons difficult.Conclusions:Bromfenac ophthalmic solution 0.09% dosed once daily is clinically safe and effective for the treatment of ocular inflammation and the reduction of ocular pain associated with cataract surgery.Trial registration: ClinicalTrials.gov identifier: NCT00704418.Trial registration: ClinicalTrials.gov identifier: NCT00853970.

Ketorolac tromethamine 0.4% to relieve eye pain and inflammation following cataract extraction and keratorefractive surgery

Ketorolac tromethamine ophthalmic solution, a NSAID, demonstrated analgesic activity when administered systemically. The original 0.5% formulation was shown to reduce inflammation and pain, as well as general discomfort after cataract and keratorefractive surgery. A reformulation that contains 20% less active ingredient than the original was approved for the reduction of ocular pain and burning/stinging following corneal refractive surgery. Ketorolac tromethamine 0.4% is as effective as ketorolac tromethamine 0.5% to control inflammation after cataract surgery (including prevention of cystoid macular edema) as shown in different clinical trials. Comparisons to other NSAIDs for pain control after keratorefractive procedures, such as laser-assisted in situ keratomileusis and photorefractive keratectomy, have also been reported. The purpose of this study was to review the action of ketorolac tromethamine 0.4% in the relief of eye pain and inflammation after cataract extraction and keratorefractive surgery.

Ketorolac tromethamine 0.4% as a treatment for allergic conjuctivitis

Background: Acular LS (ketorolac tromethamine 0.4%) ophthalmic solution, a reformulation of the original Acular (ketorolac tromethamine 0.5%), is indicated for the reduction of ocular pain and burning/stinging following corneal refractive surgery. Objective: This manuscript will review the off-label application of this topical NSAID medication as a treatment for allergic conjunctivitis. Methods: An extensive MedLine search was undertaken to evaluate data on the use of ketorolac for allergic conjunctivitis. Data on both human and animal data were reviewed. Results/conclusions: Studies have demonstrated that ketorolac 0.4% has equivalent efficacy to ketorolac 0.5%. Several studies have demonstrated that ketorolac effectively treats allergic conjunctivitis. Ketorolac 0.4% is effective when used as either monotherapy or as adjunct therapy to steroids.

The Systemic Safety of Bromfenac Ophthalmic Solution 0.09%

The aim of this study was to evaluate the systemic safety of a commercially available bromfenac ophthalmic solution 0.09% for the treatment of postoperative inflammation and reduction of ocular pain in subjects who have undergone cataract extraction. Two phase III, multicenter, randomized, double-masked, parallel, placebo-controlled, clinical trials were conducted under a common protocol. These data were pooled for analysis. The setting for this study was a series of multicentered, private, and university-affiliated ophthalmology clinics in the United States. A total of 527 subjects were sequentially assigned, according to a computer-generated randomization list (2:1) to either bromfenac (n = 356) or placebo (n = 171). Potential subjects were excluded if using nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, anticoagulants, or with uncontrolled ocular or systemic disease, preexisting ocular inflammation, surgical complications, or liver chemistry values of > or =Grade 1 according to World Health Organization Common Toxicity Criteria scoring. Subjects who underwent cataract surgery without prior anti-inflammatory treatment and had a postsurgical Summed Ocular Inflammation Score (SOIS) of > or =3 were treated with either bromfenac or placebo. Subjects self-instilled 1 drop of the assigned test agent twice-daily for 14 days and were followed for an additional 14 days for safety evaluation. Safety data were collected and the results for systemic safety are reported in this paper. Five hundred and twenty-seven (527) subjects comprised the safety population. A total of 290 of 356 bromfenac and 93 of 171 placebo subjects received 28 doses of test agent. No clinically significant treatment-related systemic adverse effects or changes in liver chemistries were observed. Bromfenac ophthalmic solution 0.09% demonstrated neither treatment-related systemic adverse events nor evidence of hepatic toxicity.

Bromfenac Ophthalmic Solution 0.09% (Xibrom) for Postoperative Ocular Pain and Inflammation

To evaluate the efficacy and ocular safety of bromfenac ophthalmic solution 0.09% (Xibrom) for the treatment of postoperative inflammation and reduction of ocular pain in subjects who have undergone cataract extraction (CE). Two phase III, multicenter, randomized, double-masked, parallel, placebo-controlled clinical trials were conducted under a common protocol. Data were pooled for analyses. Five hundred twenty-seven subjects were sequentially assigned, according to a computer-generated randomization list (2:1), to bromfenac (n = 356) or a placebo (n = 171). Subjects who underwent cataract surgery without prior antiinflammatory treatment with a postsurgical Summed Ocular Inflammation Score (SOIS) of > or =3 were treated with either bromfenac or the placebo, instilled twice daily for 14 days in the study eye, and observed for an additional 14 days for safety evaluation. Cleared ocular inflammation with a SOIS of 0 (cells< or =5 and absence of flare after 14 days of treatment). Secondary outcomes included time to resolution of ocular inflammation, time to resolution of ocular pain, proportion of subjects with photophobia, and ocular adverse events. Baseline characteristics were comparable between groups for age, gender, and race. The baseline mean SOIS was 3.7 in both groups. A greater proportion of bromfenac (64.0%) than placebo subjects (43.3%) achieved complete clearance of ocular inflammation at study day 15 (P<0.0001). The effect of bromfenac on clearance of ocular inflammation was as early as study day 3 after initiation of treatment, compared with the placebo (8.4% vs. 1.2%, P = 0.0012). The median time to resolution of ocular pain was 2 days (bromfenac) versus 5 days (placebo) (P<0.0001). Numbers of most ocular adverse events were lower for the bromfenac group than for the placebo group. Eye irritation was reported in a lower percentage of subjects for bromfenac (2.5%) versus placebo (4.7%), as were burning and stinging (1.4% vs. 2.5%), and photophobia (2.0% vs. 11.1%). Bromfenac ophthalmic solution 0.09% effectively and rapidly cleared ocular inflammation and reduced ocular pain after CE. There were no serious ocular adverse events, and fewer adverse events were reported for the bromfenac group.