New Look at Ocular Inflammation Control – Powerful and Fast-acting Twice-daily Bromfenac for a Novel Standard in the Treatment of Inflammation

Abstract

Inflammation in the eye arising from various factors -including allergy, infection, injury and surgery -can have serious consequences, and can continue long after the cause is removed, resulting in permanently damaged vision. The treatment of ophthalmic inflammation after surgery has traditionally consisted of topical corticosteroids, but adverse events such as delayed healing, rise in intraocular pressure and increased susceptibility to microbial infections have driven the search for alternative treatments. Non-steroidal anti-inflammatory drugs (NSAIDs) have been used as alternatives to steroid treatments but also have limitations and cause adverse events. Bromfenac has emerged as a potent and safe treatment for inflammation after cataract surgery. Its unique chemical structure makes it a highly lipophilic molecule that penetrates all major ocular tissues in a rapid and sustained manner. It is also a potent inhibitor of the enzyme cyclo-oxygenase-2, which is believed to be the primary mediator of ocular inflammation. These properties permit less frequent dosing (twice-daily [BID]) and greater patient tolerability. A body of efficacy and safety data support use of bromfenac in this indication and it compares favourably with other NSAIDs and steroids in limiting post-operative inflammation. NSAIDs and corticosteroids have different, potentially synergistic effects. However, benefits specific to NSAIDs include lowering prostaglandin E-induced intraocular pressure elevation, no increased risk of secondary infections and stabilisation of the blood-aqueous barrier. With increasing demand for ophthalmic surgery, bromfenac and other treatments are likely to be important components in the treatment of inflammatory conditions after cataract surgery, decreasing pain and contributing to favourable visual outcomes. KeywordsBromfenac, ophthalmic non-steroidal anti-inflammatory drugs, ocular inflammation, cystoid macular oedema, ocular pain Treatments for Ocular InflammationThe two main treatments for ocular inflammation are topical corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs).Corticosteroids interfere with the activity of phospholipase A 2 , thereby inhibiting the release of arachidonic acid metabolites, includingPGs.2 By contrast, NSAIDs non-specifically and irreversibly inhibit the synthesis of PGs by directly interfering with the activity of COX-1 and COX-2 (see Figure 1). 2 CorticosteroidsThe corticosteroids, which are considered the gold standard for the treatment of ocular inflammation, are associated with an increased incidence of adverse events that warrant their judicious use. Most NSAIDs are weakly acidic drugs that ionise at the pH of lacrimal fluid, thus limiting their permeability through the ionic cornea, which has an isoelectric point (pI) of 3.2. 6 Reducing the pH of the formulation increases the un-ionised fraction of the drug, enhancing permeation. Being acidic, NSAIDs are inherently irritant, and reducing the pH of the formulation further increases their irritation potentia...

A prospective evaluation of efficacy and safety of topical bromfenac 0.09% over topical flurbiprofen 0.03% after cataract surgery

“…Therefore, the need for anti-inflammatory treatment arises. 13 Topical anti-inflammatory drugs (corticosteroids and NSAIDs) are preferred over systemic preparations for ophthalmic purposes as they are proved to be safer. The use of systemic NSAIDs has been associated with serious adverse events like hepatotoxicity, peptic ulcer, gastrointestinal haemorrhage, hepatic and biliary disorders.…”

Pathogenesis of Pseudophakic Cystoid Macular Oedema

“…[99][100][101]103,105,111 However, these studies usually have been poorly designed and, although in general they have proven the effectiveness of use of this type of medication in preventing both angiographic and clinical CMO, 25 The two more recently introduced drugs in the European marketnepafenac and bromfenac -have some potential advantages, due to rapid penetration in ocular tissues related to high corneal permeability. 100,[112][113][114][115][116][117] They have been developed to exploit the anti-inflammatory potency of amfenac within the eye. Amfenac is a highly potent inhibitor of both COX-1 and COX-2, but it is unable to penetrate the corneal epithelium.…”

“…Bromfenac is structurally identical to amfenac but with some specific differences that make it a highly lipophilic molecule, which facilitates its rapid penetration through the cell membrane of various tissues, including ocular, to obtain sustained drug levels, increasing the duration of analgesic and anti-inflammatory activity. 112,117 Another point of discussion is related to the timing of the use of steroids and NSAIDs before surgery. 93 It is now considered essential to use NSAIDs and/or steroids, in risk cases, before surgery during a variable period according to each specific situation.…”

“…Topical NSAIDs are classified into different groups based on their chemical composition. There is some difficulty in obtaining an idealformulation of NSAIDs to be applied topically to the eye 112. Some are considered too toxic to be used in the eye; others are weakly acid thus they have a limited permeability through the cornea and, on the other hand, the acid drugs are a potential irritant.…”

“…Some are considered too toxic to be used in the eye; others are weakly acid thus they have a limited permeability through the cornea and, on the other hand, the acid drugs are a potential irritant. There are, however, at the moment, several NSAIDs approved in EU for treatment of post-operative inflammation after cataract surgery: ketorolac, diclofenac, flurbiprofen, indometacin, nepafenac and bromfenac 112.…”