Ophthalmic Nonsteroidal Anti-inflammatory Drugs Research Articles

Comparison of drugs belonging to the group of ophthalmic non-steroidal anti-inflammatory drugs

Ophthalmic non-steroidal anti-inflammatory drugs are non-steroidal anti-inflammatory drugs used to treat or prevent eye inflammation. Their main action is to relieve symptoms such as pain, redness and swelling that can be caused by eye diseases, injuries or eye surgery. Non-steroidal anti-inflammatory drugs used in ophthalmology include substances such as diclofenac, ketorolac, bromfenac and nepafenac. So far, many studies have been published comparing the effectiveness of various systemic and local non-steroidal anti-inflammatory drugs. This work contains a comparative analysis of the above-mentioned substances in terms of their use and effectiveness in ophthalmology.

Retrospective evaluation of the incidence of gastrointestinal bleeding in dogs receiving ophthalmic nonsteroidal anti-inflammatory drugs.

To report the incidence of gastrointestinal (GI) bleeding and associated risk factors in a population of dogs receiving ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs). Medical records of dogs prescribed ophthalmic NSAIDs (cases), dogs receiving systemic NSAIDs alone and dogs receiving systemic prednisone alone (controls). Data were collected retrospectively from the medical records of 204 dogs prescribed ophthalmic NSAIDs (diclofenac, ketorolac, or flurbiprofen), which were subdivided based on if they received any concurrent systemic NSAIDs or glucocorticoids, 136 dogs receiving a systemic NSAID (carprofen or meloxicam) alone, and 151 dogs receiving a systemic glucocorticoid (prednisone) alone at a referral hospital from 2015 to 2019. Gastrointestinal bleeds developed in 8/79 (10.1%) of topical NSAID-only cases, 10/136 (7.4%) of systemic NSAID controls, and 14/151 (9.3%) of systemic glucocorticoid controls, with no significant difference between the three groups (p = .6103). There were no significant differences in GI bleed rates between cases treated with ketorolac, diclofenac, or flurbiprofen (p = .160), although severe GI bleeding was only seen in ketorolac-treated dogs. Presence of a known concurrent risk factor for GI bleeding was significantly associated with the development of GI bleed in dogs on ophthalmic NSAIDs (p = .032). Dogs treated with ophthalmic NSAIDs developed GI bleeding at a frequency comparable to dogs receiving systemic NSAIDs or systemic glucocorticoids alone, suggesting that dogs receiving ophthalmic NSAIDs may be at increased risk of GI bleeding.

Fill levels, cost comparisons, and expulsion force requirements of commonly used topical ophthalmic nonsteroidal anti-inflammatory drugs.

To determine volume fill levels, estimated costs, and force expulsion requirements per bottle of topical ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) commonly perioperatively in the United States. Tertiary care academic medical center. Prospective laboratory investigation. 8 commercially available NSAIDs (3 branded, 5 generic) were tested: branded bromfenac 0.07%, generic bromfenac 0.09%, diclofenac 0.1%, flurbiprofen 0.03%, generic ketorolac 0.5%, branded ketorolac 0.5%, ketorolac 0.47%, and branded nepafenac 0.3%. 10 bottles of each medication were tested, with an additional bottle tested for expulsion force requirements. A double-blinded method was used to measure the actual bottle fill volume and number of drops per bottle. The total cost per drop was calculated using published cash prices. Force requirements were measured using a customized force gauge apparatus. Formulations were compared using the Kruskal-Wallis test, followed by pairwise comparisons with the Dwass, Steel, Critchlow-Fligner Method. 2 branded NSAIDs (bromfenac and nepafenac) had slightly lower-than-sticker volumes while generics other than ketorolac had higher-than-sticker volumes. Diclofenac and branded bromfenac had the highest and lowest adjusted number of drops respectively. Generic bromfenac and generic ketorolac had the highest and lowest adjusted volume compared with sticker volume respectively. Branded bromfenac was the most expensive medication, while generic diclofenac was the least expensive. Force expulsion requirements varied significantly among generic and branded NSAIDs. Volume fill levels, patient-incurred costs, and expulsion force requirements per bottle of topical NSAID medications vary significantly. Surgeons may wish to consider these factors when deciding how best to use these medications perioperatively.

Prophylaxis of posterior capsule opacification through autophagy activation with indomethacin-eluting intraocular lens.

Posterior capsule opacification (PCO) is the most common long-term postoperative complication of cataract surgery, leading to secondary vision loss. Optimized intraocular lens (IOL) structure and appropriate pharmacological intervention, which provides physical barriers and biological inhibition, respectively, can block the migration, proliferation, and epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) for PCO prophylaxis. Herein, a novel indomethacin-eluting IOL (INDOM-IOL) with an optimized sharper edge and a sustained drug release behavior was developed for PCO prevention. Indomethacin (INDOM), an ophthalmic non-steroidal anti-inflammatory drug (NSAID) used for postoperative ocular inflammation, was demonstrated to not only be able to suppress cell migration and down-regulate the expression of cyclooxygenase-2 (COX-2) and EMT markers, including alpha-smooth muscle actin (α-SMA) and cyclin D1, but also promote the autophagy activation in LECs. Additionally, autophagy was also verified to be a potential therapeutic target for the down-regulation of EMT in LECs. The novel IOL, serving as a drug delivery platform, could carry an adjustable dose of hydrophobic indomethacin with sustained drug release ability for more than 28 days. In the rabbit PCO model, the indomethacin-eluting IOL showed excellent anti-inflammatory and anti-PCO effects. In summary, indomethacin is an effective pharmacological intervention in PCO prophylaxis, and the novel IOL we developed prevented PCO in vivo under its sustained indomethacin release property, which provided a promising approach for PCO prophylaxis in clinical application.

Formulation And Evaluation of Controlled Release Bromfenac Sodium Ocular Insert

According to the World Health Organization, cataract operations are performed on one million people per year [1]. After cataract surgery, however, most patients still experience physiologically severe postoperative ocular inflammation. Uncontrolled intraocular inflammation causes discomfort, delayed recovery, poor visual results, and even more severe problems such as cystoid macular oedema and synechiae due to inflammatory cells and cytokines entering the aqueous humour. Topical non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat non-infectious ocular inflammation after ophthalmic surgery. As a result, NSAIDs appear to be potentially useful drugs for cataract surgery. [2] The U.S Food and Drug Administration has approved four ophthalmic NSAIDs to treat postoperative ocular inflammation followed by cataract surgery: bromfenac sodium, diclofenac sodium, Ketorolac tromethamine, and nepafenac.[3] The first approved NSAID for treating anterior chamber inflammation during cataract surgical treatment is bromfenac ophthalmic solution. Bromfenac is a more potent drug than other drugs for treating ocular inflammation. [4] The drug-loaded eye drop is easy to use. However, it has the inherent disadvantage that most medication is almost immediately diluted away in the tear film when the eye drops are introduced into the cul-de-sac and quickly exhausted from the precorneal cavity's constant tear flow. This process occurs more intensively in swollen eyes than in normal eyes and lachrymal-nasal drainage. [5,6] To avoid the previously stated side effects and increase the drug's effectiveness, a novel approach of an ocular insert that increases the drug's contact time in the eye should be chosen, thus improving patient compliance by increasing bioavailability and reducing frequent administration. [7] Ophthalmic inserts are skinny discs of polymeric substances that fit into the upper or lower conjunctiva sac. They have compensations over the conventional dosage forms and possess amplified ocular residence, discharge the drugs at a slow and consistent momentum, are capable of delivering precise dosing, lack preservatives, have augmented shelf life, and reduced systemic incorporation. [8] Our research intended to fabricate bromfenac sodium ocular inserts to amplify the contact time and offer a controlled release model that could advance patient compliance, cut dosing frequency, and attain superior curative usefulness.

Use of topical bromfenac for treating ocular pain and inflammation beyond cataract surgery: a review of published studies.

Topical ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat postoperative inflammation and pain following cataract surgery and for treatment and prophylaxis of pseudophakic cystoid macular edema (CME). Bromfenac is a brominated NSAID with strong in vitro anti-inflammatory potency. Like other ophthalmic NSAIDs, bromfenac is often used outside of the cataract surgery setting. This paper provides an overview of bromfenac’s preclinical ocular pharmacology and pharmacokinetics, followed by a review of 23 published clinical studies in which various marketed bromfenac formulations were used for conditions other than cataract surgery or pseudophakic CME. These include: post-refractive eye surgery; macular edema associated with diabetes, uveitis, or retinal vein occlusion; inflammation associated with age-related macular degeneration; pain related to intravitreal injections; and other ocular anterior segment and surface disorders with an inflammatory component. The published evidence reviewed supports the safety and effectiveness of bromfenac in these additional ophthalmic indications. Bromfenac was well tolerated when given alone or in combination with intravitreal anti-vascular endothelial growth factor agents, topical corticosteroids, or topical mast-cell stabilizers. The most common adverse event reported was ocular irritation. No serious adverse events (ie, corneal epithelial disorders) were reported, although the majority of studies did not systematically evaluate potential side effects. Corneal complications, such as melts reported with diclofenac and ketorolac, were not observed with bromfenac in the studies. In summary, published study data support the clinical utility of bromfenac in various ocular disorders beyond post-cataract surgery. Additional studies are warranted to further define the potential role of bromfenac ophthalmic solution in clinical practice.

Efficacy and safety of bromfenac 0.075% formulated in DuraSite for pain and inflammation in cataract surgery

ABSTRACTIntroduction: Bromfenac is a topical ophthalmic non-steroidal anti-inflammatory drug (NSAID) used to reduce pain and treat post-operative inflammation after cataract surgery. Bromfenac 0.075% in the DuraSite™ vehicle is a newly-approved formulation which has been shown to be efficacious and safe for use in cataract surgery to reduce pain and treat inflammation. It has been shown to have a slightly better posterior segment ocular bioavailability compared to similar topical ophthalmic NSAIDs. However, there is a paucity of studies investigating its role in the prevention and treatment of post-operative pseudophakic cystoid macular edema.Areas covered: In this review, the authors provide an overview of similar products available, describe the novelty of bromfenac 0.075% in the DuraSite vehicle, and discuss the relevant clinical studies to determine if the formulation is safe and efficacious.Expert opinion: Bromfenac 0.075% in the DuraSite vehicle is a new topical ophthalmic medication which has been approved by the FDA for the prevention of pain and treatment of post-operative inflammation. It provides cataract surgeons with an additional medication for cataract surgery. However, no robust studies have been performed showing the effect that it has on the reduction or prevention of post-operative pseudophakic cystoid macular edema.

Ophthalmic Nonsteroidal Anti-Inflammatory Drugs as a Therapy for Corneal Dystrophies Caused by SLC4A11 Mutation.

SLC4A11 is a plasma membrane protein of corneal endothelial cells. Some mutations of the SLC4A11 gene result in SLC4A11 protein misfolding and failure to mature to the plasma membrane. This gives rise to some cases of Fuchs' endothelial corneal dystrophy (FECD) and congenital hereditary endothelial dystrophy (CHED). We screened ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) for their ability to correct SLC4A11 folding defects. Five ophthalmic NSAIDs were tested for their therapeutic potential in some genetic corneal dystrophy patients. HEK293 cells expressing CHED and FECD-causing SLC4A11 mutants were grown on 96-well dishes in the absence or presence of NSAIDs. Ability of NSAIDs to correct mutant SLC4A11 cell-surface trafficking was assessed with a bioluminescence resonance energy transfer (BRET) assay and by confocal microscopy. The ability of mutant SLC4A11-expressing cells to mediate water flux (SLC4A11 mediates water flux across the corneal endothelial cell basolateral membrane as part of the endothelial water pump) was measured upon treatment with ophthalmic NSAIDs. BRET-assays revealed significant rescue of SLC4A11 mutants to the cell surface by 4 of 5 NSAIDs tested. The NSAIDs, diclofenac and nepafenac, were effective in moving endoplasmic reticulum-retained missense mutant SLC4A11 to the cell surface, as measured by confocal immunofluorescence. Among intracellular-retained SLC4A11 mutants, 20 of 30 had significant restoration of cell surface abundance upon treatment with diclofenac. Diclofenac restored mutant SLC4A11 water flux activity to the level of wild-type SLC4A11 in some cases. These results encourage testing diclofenac eye drops as a treatment for corneal dystrophy in patients whose disease is caused by some SLC4A11 missense mutations.

A Case of Allergic Urticaria After Ophthalmic Nepafenac Use.

A 21-year-old male patient with no history of systemic disease or drug use presented to our clinic with redness and pain in the right eye. Best corrected visual acuity was 20/20 in both eyes. Inflamed pinguecula was observed on slit-lamp examination and the patient was prescribed ophthalmic nepafenac eye drops. After instilling the drops that day and the next day, the patient presented again due to pruritus and rash. Upon consultation with the dermatology department, the patient was diagnosed with drug-induced allergic urticaria and the nepafenac drops were discontinued. Although urticaria has been reported as a side effect after systemic non-steroidal anti-inflammatory drug (NSAID) use, such a reaction has not been reported with an ophthalmic NSAID and ours is the first reported case of urticaria following ophthalmic nepafenac use. This unique case highlights the fact that ophthalmologists must also keep urticaria in mind as a potential side effect when prescribing this drug.

Twice-Daily vs. Once-Daily Dosing with 0.075% Bromfenac in DuraSite: Outcomes from a 14-Day Phase 2 Study.

IntroductionBromfenac is a well-known topical ophthalmic nonsteroidal anti-inflammatory drug (NSAID) that is commercialized in the USA and other regions of the world. A new formulation, 0.075% bromfenac in DuraSite®, was developed to treat postoperative inflammation and reduce pain in patients who have undergone cataract surgery. We hypothesized that efficacy and safety would be enhanced with twice-daily (BID) dosing compared to once-daily (QD) dosing.MethodsThis was a multicenter, double-masked, comparative study in which 40 and 45 subjects were randomized to groups receiving BID dosing and QD dosing, respectively. Subjects self-instilled the study drug for 14 days postoperative and were followed for an additional 2-week evaluation phase. The primary efficacy endpoint was the proportion of subjects with an anterior chamber cell (ACC) grade of 0 at day 15.ResultsA total of 45 subjects had cleared ACC (grade “0”) at day 15, of whom 21 were in the BID group (52.5%) and 24 were in the QD group (53.5%). A secondary analysis found 7/40 (17.5%) subjects in the BID group and 10/45 (22.2%) subjects in the QD group achieved an ACC grade of 0 at day 8. There were more adverse events in the QD group (n = 16) than in the BID group (n = 12).ConclusionSimilar outcomes were observed for subjects using Bromfenac 0.075% in DuraSite® in the BID and QD dosing regimens for the treatment of post-cataract surgery inflammation.Trial registrationClinicalTrials.gov identifier, NCT01190878.FundingInSite Vision (now a division of Sun Pharma).

Comparison of the efficacy and patients' tolerability of Nepafenac and Ketorolac in the treatment of ocular inflammation following cataract surgery: A meta-analysis of randomized controlled trials.

As a new ophthalmic non-steroidal anti-inflammatory drug (NSAID) with prodrug structure, Nepafenac was supposed to have a better efficacy than conventional NSAIDs both in patients’ tolerability and ocular inflammation associated with cataract surgery. However, many current studies reached contradictory conclusions on the superiority of Nepafenac over Ketorolac. The objective of our study is to evaluate the efficacy and patients’ tolerability of Nepafenac and Ketorolac following cataract surgery. To clarify this, we conducted a meta-analysis of randomized controlled trials. Eleven articles were included in this study. The dataset consisted of 1165 patients, including 1175 cataract surgeries. Among them, 574 patients were in the Nepafenac group and 591 in the Ketorolac group. Our analysis indicated that these two drugs were equally effective in controlling post cataract surgery ocular inflammation, reducing macular edema, achieving a better visual ability and maintaining intraoperative mydriasis during cataract surgery. However, Nepafenac was more effective than Ketorolac in reducing the incidence of postoperative conjunctival hyperemia and ocular discomfort. This meta-analysis indicated that topical Nepafenac is superior to Ketorolac in patients’ tolerability following cataract surgery. However, these two drugs are equally desirable in the management of anterior chamber inflammation, visual rehabilitation and intraoperative mydriasis. Given the limitations in our study, more researches with larger sample sizes and focused on more specific indicators such as peak aqueous concentrations of drugs or PEG2 levels are required to reach a firmer conclusion.

Topical bromfenac for post-cataract extraction: A systematic review and pooled analysis

Bromfenac, a promising ophthalmic non-steroidal anti-inflammatory drug, has been used once daily for postoperative ocular inflammation and pain with satisfying efficacy, however, no integrated conclusion on its safety in clinical settings has been drawn. The purpose of this pooled analysis is to investigate the safety and efficacy of once daily bromfenac for ocular inflammation and pain among patients after cataract extraction (CE). MEDLINE, PsycINFO, Scopus, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to September 2014. Randomized controlled trials (RCTs) that studied topical bromfenac after CE were analyzed. Included studies were systemically reviewed, and effects were summarized using odds ratio (OR) with suitable effect model. Four RCTs involving 2294 participants were included. Topical bromfenac significantly increased the proportion of cleared ocular inflammation (OR, 2.37; 95% confidence interval [CI], 1.83–3.07; P <0.00001), ocular pain free (OR, 5.14; 95% CI, 4.07–6.49; P <0.00001), and decreased risk of overall adverse events (OR, 0.47; 95% CI, 0.38–0.58; P <0.00001). Bromfenac has been shown to be a safe and effective treatment for postoperative pain and inflammation in subjects undergoing CE. This is evidenced by the lower incidence of adverse events and the low scores for ocular pain and inflammation across multiple RCTs. However, demographics, co-morbidities of study participants, and the amount of co-medication were not reported, these possible sources of heterogeneity should be examined in future clinical trials.

Bromfenac ophthalmic solution for the treatment of postoperative ocular pain and inflammation: safety, efficacy, and patient adherence.

Ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used by clinicians to manage ocular inflammation and pain following cataract surgery. Over the past decade, the US Food and Drug Administration has approved multiple topical NSAIDs for these purposes, including several reformulated products. One of these medications, bromfenac ophthalmic solution, has a long and extensive history, with proven efficacy and safety in patients following cataract surgery. The evolution of bromfenac ophthalmic solution over the years has involved either lowering the concentration of the active ingredient or extending the dosing interval to improve patient adherence/compliance. This review will focus on the history and progression of bromfenac ophthalmic solution and report the available patient preference and adherence data regarding this ocular NSAID throughout its evolution.

Comparative study of the ocular efficacy and safety of diclofenac sodium (0.1%) ophthalmic solution with that of ketorolac tromethamine (0.5%) ophthalmic solution in patients with acute seasonal allergic conjunctivitis

Background:Seasonal allergic conjunctivitis (SAC) is the most common and most prevalent of allergic disorders which afflict the ocular surface. Of the several treatments available, ophthalmic non-steroidal anti-inflammatory drugs, are generally very safe and tolerable.Aim:The aim of this study is to compare the ocular efficacy and safety of diclofenac sodium (0.1%) ophthalmic solution with that of ketorolac tromethamine (0.5%) ophthalmic solution in patients with acute SAC.Materials and Methods:Sixty patients with signs and symptoms of SAC were evaluated in an open, randomized, parallel group study. The principle symptoms (ocular itching, burning, discharge, photophobia) and signs (ocular inflammation, lid edema, chemosis, conjunctival mucous, keratitis) were evaluated.Study Design:Patients were randomized into two groups of 30 each. Patients in group A received one drop of diclofenac sodium 0.1% and patients in group B received ketorolac tromethamine 0.5% in both the eyes four times a day for fourteen days. Evaluations were performed at day 0, 3, 7 and 14 of the therapy. At each visit, the signs and symptoms were rated using a scale from 0-3 (mild-1, moderate-2 and severe-3).Results:Significant clinical and statistical reductions in signs and symptoms from baseline were observed in both groups. Diclofenac sodium 0.1% was superior to ketorolac tromethamine 0.5% in reducing ocular itching (P < 0.05) and ocular inflammation (P < 0.05), at the final examination.Conclusion:Diclofenac sodium showed statistically significant better results at day 3 and 7 compared to ketorolac.

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.

Current Use of Non-steroidal Anti-inflammatory Drugs in the Treatment of Ocular Inflammation Related to Cataract Surgery

Ocular inflammation and pain are a common consequence of cataract surgery, and if left untreated, may lead to extensive ocular damage, resulting in impaired vision as well as decreased satisfaction with the procedure. Effective management of ophthalmic inflammation after surgery is therefore vital. Topical ophthalmic non-steroidal anti-inflammatory drugs (NSAIDs) have become a mainstay of management of ocular pain and inflammation as a result of their anti-inflammatory activity, analgesic property and established safety record. Numerous studies have demonstrated the efficacy of topical NSAIDs in post-operative prevention of ocular inflammation, inhibition of intra-operative miosis, reduction of pain associated with cataract surgery and pre-operative use to prevent cystoid macular oedema. Studies have also indicated that NSAIDs and steroids act synergistically when administered together, and that a combination of steroid and NSAID therapy is recommended to achieve successful outcomes. With appropriate administration, NSAIDs are safe and effective therapeutic agents, which rarely result in serious local and systemic responses.

Review of Bromfenac Ophthalmic Solution 0.09 % Once-daily

Bromfenac ophthalmic solution 0.09 % (BROMDAY™, ISTA Pharmaceuticals, Inc., Irvine, CA) is the first and only once-daily topical ophthalmic non-steroidal anti-inflammatory drug (NSAID) approved by the Food and Drug Administration for the treatment of post-operative pain and inflammation following cataract surgery. Topical NSAIDs are important following surgery to enhance patient comfort and limit inflammation, which may otherwise restrict visual rehabilitation. In a recently published study looking at Early Treatment Diabetic Retinopathy Study (ETDRS) acuities and macular optical computed tomographies (OCTs) in the post-operative period, bromfenac had lower post-operative macular volumes and retinal thicknesses compared with nepafenac, which correlated with a separate retrospective study that found fewer clinical cases of cystoid macular edema (CME) following uneventful phacoemulsification. Since regulatory approval in Japan (2000) and the US (2005 and 2010), bromfenac has been shown to be a safe and effective medication, with more than 26 million ophthalmic uses. Once-daily dosing may confer improvements in compliance and reduce exposure to preservatives, which have been shown to lead to corneal toxicity.

Ex vivo corneal epithelial wound healing following exposure to ophthalmic nonsteroidal anti-inflammatory drugs

Purpose:Ketorolac 0.45% is a new formulation of topical ketorolac in which preservative (benzalkonium chloride, BAK) was removed and carboxymethylcellulose (CMC) was added to improve tolerability and reduce dosing frequency. This study compared the effects of ketorolac 0.45% on corneal wound healing to prior ketorolac formulations (0.4% and 0.5%), bromfenac 0.09%, and nepafenac 0.1%.Methods:Two parallel-group comparisons were performed in series. A 5-mm central epithelial wound was made in fresh porcine corneas. After 24 hours in minimum essential medium (MEM), corneas were incubated for 10 minutes with study drugs, Triton X-100 1% (positive control), or MEM (negative control), followed by 24 hours in MEM. The remaining wound area was stained, photographed, and quantified (pixels). Study 1 compared ketorolac 0.45% to ketorolac 0.4% and ketorolac 0.5%. Study 2 compared ketorolac 0.45% to bromfenac 0.09% and nepafenac 0.1%.Results:The mean (±SD) original wound area was 200,506 ± 4,363 pixels, which was reduced to 59,509 ± 4850 at 48 hours after exposure to Triton X-100 1%. In study 1, the mean remaining wound areas at 48 hours in pixels were 2969 ± 1633 with MEM, 586 ± 299 with ketorolac 0.45% (significantly reduced, P < 0.05 vs all other treatments), 10,228 ± 7541 with ketorolac 0.4%, and 50,674 ± 33,409 with ketorolac 0.5% (significantly enlarged, P < 0.05 vs MEM). In study 2, the mean remaining wound areas at 48 hours were 565 ± 1263 with MEM, 322 ± 229 with ketorolac 0.45% (significantly reduced, P < 0.01 vs bromfenac 0.09% and nepafenac 0.1%), 29,093 ± 14,295 with bromfenac 0.09% (significantly enlarged, P <0.01 vs MEM) and 47,322 ± 13,736 with nepafenac 0.1% (significantly enlarged, P < 0.01 vs MEM and vs bromfenac 0.09%).Conclusion:Corneas treated with ketorolac 0.45% healed as rapidly as those treated with MEM, likely secondary to addition of CMC and removal of BAK. In the ex vivo corneal organ culture model, ketorolac 0.45% had statistically less impact on corneal re-epithelialization than prior ketorolac formulations (0.4% and 0.5%), bromfenac 0.09%, and nepafenac 0.01%.

Redefining the Treatment Paradigm for Post-operative Inflammation Control – The Role of Topical Non-steroidal Anti-inflammatory Drugs

Topical ophthalmic non-steroidal anti-inflammatory drugs (NSAIDs) are used in the treatment of post-operative ocular inflammation and pain following cataract surgery and for some other clinical applications of ophthalmology, including cystoid macular oedema. Products vary by their pharmacological properties, clinical efficacy and tolerability, which affect their place in therapy for new agents in Europe. The pharmacological properties of topical ophthalmic NSAIDs and their place in current treatment of post-operative ocular inflammation are discussed in this article, focussing on bromfenac, which has been submitted for approval by the European Medicines Agency (EMEA).

Efficacy of ophthalmic nonsteroidal antiinflammatory drugs in suppressing anterior capsule contraction and secondary posterior capsule opacification

To evaluate the efficacy of ophthalmic nonsteroidal and steroidal antiinflammatory drugs in preventing anterior capsule contraction and secondary posterior capsule opacification (PCO) using an experimental cataract model. Department of Ophthalmology, Dokkyo Medical University, Tochigi, Japan. Eight-week-old albino rabbits weighing about 2 kg each had phacoemulsification and intraocular lens implantation. After surgery, the rabbits were divided into 3 treatment groups: diclofenac sodium ophthalmic solution, bromfenac sodium ophthalmic solution, and betamethasone ophthalmic solution. In each group, the ophthalmic solution was applied to the left eye of each rabbit twice daily; the right eye served as an untreated control. To evaluate anterior capsule contraction, the percentage of incised anterior capsule opening area was calculated on diaphanoscopic images obtained with an EAS-1000 anterior segment analyzer. For evaluation of PCO, a tissue section was stained with hematoxylin-eosin and observed under a light microscope. The PCO was quantified on the basis of the thickness of the lens epithelial cell layer on the central subcapsular area and compared among groups. Fifteen albino rabbits were used in the study. Treatment with diclofenac sodium and bromfenac sodium ophthalmic solution prevented progression of anterior capsule contraction and PCO. Treatment with bromfenac ophthalmic solution did not prevent either complication. Postoperative treatment with ophthalmic nonsteroidal antiinflammatory drug solutions prevented anterior capsule contraction and PCO in rabbit eyes.