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Ocular Diclofenac

A Review of its Pharmacology and Clinical Use in Cataract Surgery, and Potential in Other Inflammatory Ocular Conditions

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Abstract

Synopsis

Diclofenac sodium is a potent nonsteroidal anti-inflammatory drug with analgesic activity. When instilled as a topical 0.1% solution in a limited number of patients undergoing cataract surgery, diclofenac limits surgically induced miosis, reduces signs of ocular inflammation, does not cause elevations in intraocular pressure, and reduces the occurrence and severity of cystoid macular oedema. Preliminary findings suggest a niche for topical diclofenac in other ocular inflammatory conditions such as iritis, episcleritis and conjunctivitis, although its efficacy in these areas awaits confirmation. The drug appears well tolerated, apart from a transient burning sensation after instillation in some patients.

Ocular diclofenac thus appears well suited as a local anti-inflammatory adjunct to cataract surgery, and may be useful in some other inflammatory ocular conditions.

Pharmacodynamic Properties

Tissue injury causes breakdown of phospholipids to arachidonic acid which is converted either to prostaglandins by cyclo-oxygenase, or to hydroxy acids and leukotrienes by 5-lipoxygenase. Prostaglandins have been detected in rabbit eyes following trauma, and leukotrienes in ocular tissue of patients with inflammatory eye conditions.

Diclofenac sodium (the salt of diclofenac referred to exclusively in this review) is a potent inhibitor of prostaglandin synthesis (i.e. it acts mainly through cyclo-oxygenase inhibition), as shown in various animal models, in vitro and when administered systemically in vivo. Although the in vitro effects of diclofenac on prostaglandin synthesis in eye tissue have not been documented, the drug attenuated the increases in intraocular pressure (IOP) and aqueous humour protein levels induced by various traumas when instilled in rabbit eyes in vivo, but had an equivocal effect on surgically induced miosis. Leucocyte accumulation in rabbit eyes induced by a synthetic chemotactic agent was reduced by ocular diclofenac 0.064%.

Ocular diclofenac inhibits breakdown of the blood-aqueous barrier in elderly patients, and in patients undergoing cataract surgery, possibly more effectively than the commonly used topical prednisolone.

Pharmacokinetic Properties

The pharmacokinetic profile of topically applied diclofenac is incomplete. Concentrations of diclofenac were highest in the cornea and conjunctiva of rabbit eye after instillation of eyedrops, and subsided within 1 hour.

In patients with cataracts, diclofenac penetrates into aqueous humour, with mean peak concentrations of about 130 mg/L achieved within 1 hour of eyedrop instillation. Diclofenac is highly bound to plasma proteins (⩾ 99.5%). The drug is metabolised after oral administration principally to 4-hydroxy-diclofenac, and has a mean elimination half-life of 1 to 2 hours. Pharmacokinetics of diclofenac are largely unaffected by age, or renal or hepatic impairment.

Clinical Use and Tolerability

Although relatively few trials have investigated the efficacy of ocular diclofenac as an adjunct to cataract surgery, most studies were well-designed. Diclofenac 0.1% ophthalmic solution instilled 2 to 4 times daily after cataract surgery relieved signs of ocular inflammation to a similar extent as dexamethasone 0.1% in an identical regimen, with less tendency to induce elevated IOP. IOP elevation was similar following treatment with diclofenac 0.1% or indomethacin 1%. Diclofenac 0.1% was at least as effective in relieving inflammation as prednisolone 1%.

Preoperative instillation of diclofenac 0.1% attenuated surgically induced miosis, a clinically important effect which facilitates successful surgery, and was superior to placebo, routine medications (cyclopentolate 1%, phenylephrine 10%), and indomethacin 1%. Diclofenac 0.1% in a multiple dose pre- and postoperative regimen for 6 months decreased the incidence and severity of cystoid macular oedema to a significantly greater extent than placebo.

Limited evidence suggests that ocular diclofenac ameliorates symptoms and signs of iritis/ iridocyclitis, and may have a potential role in some forms of episcleritis and conjunctivitis, and in reducing inflammation caused by laser trabeculoplasty.

Ocular diclofenac appears well tolerated, although few published data are available. Slight transient burning in the eye has been experienced by some patients, and blurred vision, hypersensitivity reactions and keratitis punctata have been reported rarely.

Dosage and Administration

The recommended regimen for preoperative use of diclofenac 0.1% eyedrops in patients undergoing cataract surgery is 1 drop up to 5 times during the 3 hours before surgery. For postoperative use, 1 drop should be instilled 3 times during the day after surgery, then 1 drop 3 to 5 times daily.

In other indications 1 drop 4 to 5 times daily is advocated.

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    Karen L. Goa & Paul Chrisp

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Various sections of the manuscript reviewed by: M. Araie, Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan; W. Behrens-Baumann, Augenklinik und Poliklinik, Georg-August-Universitat Göttingen, Göttingen, Federal Republic of Germany; P. Bhattacherjee, Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky, USA; L. Bonomi, Istituto di Clinica Oculistica, Universita degli Studi di Verona, Verona, Italy; H. Ertiirk, Department of Ophthalmology, Uludag University Faculty of Medicine, Bursa, Turkey; F.T. Fraunfelder, Casey Eye Institute, Oregon Health Sciences University School of Medicine, Portland, Oregon, USA; K. Nishi, Nishi Eye Hospital, Osaka, Japan; O. Nishi, Nishi Eye Hospital, Osaka, Japan; C.I. Phillips, Ophthalmology Unit, University of Edinburgh Department of Surgery, Edinburgh, Scotland; C.D. Quentin, Augenklinik und Poliklinik, Georg-August-Universitat Göttingen, Göttingen, Federal Republic of Germany; M.D. Trousdale, Doheny Eye Institute, Los Angeles, California, USA.

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Goa, K.L., Chrisp, P. Ocular Diclofenac. Drug & Aging 2, 473–486 (1992). https://doi.org/10.2165/00002512-199202060-00004

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