Inhibitors of the arachidonic acid cascade in the management of ocular inflammation.
At the present time, corticosteroids are still the most effective class of drugs for the treatment of ocular inflammation. However, since their prolonged use may result in severe ocular side effects, it would be therapeutically beneficial to develop nonsteroidal anti-inflammatory drugs that have similar or greater efficacy than steroids, but do not share their ocular side effects. Several currently available non-steroidal drugs have been used clinically as prophylactic or therapeutic agents for the following: 1. Prevention of pupillary constriction during intraocular surgery (cataract extraction). 2. Prevention of postoperative inflammation, i.e., incidence of anterior chamber cellular reaction and aqueous flare (breakdown of blood-aqueous barrier) and IOP rise following cataract surgery, intraocular lens implantation, and argon laser trabeculoplasty. 3. Prevention of contact lens induced corneal neovascularization. 4. Improvement of lens opacity (bendazac). 5. Prevention of cystoid macular edema following intraocular surgery. Treatment over long-term period may be effective; postoperative treatment is ineffective. 6. Prevention of conjunctival hyperemia. Some prophylactic ocular uses such as prevention of surgical miosis or postoperative fluorescein leakage have been reported to be successful. However, it is unclear whether the reported success reflected the pharmacological effects due to inhibition of the AA cascade - and hence, reflects the role of some eicosanoids in surgical miosis or postoperative fluorescein leakage - or reflect the effects of these drugs on unexplored physiological or pharmacological mechanisms. For example, pretreatment with flurbiprofen to prevent surgical miosis was based on the assumption that PGs are potent miotic agents in all mammals, including humans. It remains to be established however, whether the small reduction in the extent of pupillary miosis is due to prevention of PG synthesis by this drug or to the prevention of the synthesis of other AA products, such as prostacyclin and thromboxane or possibly to some entirely different mechanism. Prevention of post-surgical fluorescein leakage by prophylactic pre and/or post surgical treatment with a variety of nonsteroidal anti-inflammatory agents is also assumed to be due to inhibition of intraocular PG synthesis, although the possibility that it is due to prevention of the synthesis of prostacyclin or TxA2 has not been ruled out. Even more important, it has not been demonstrated that prevention of this post operative fluorescein leakage reflects the prevention or inhibition of true CME and associated loss of visual acuity.(ABSTRACT TRUNCATED AT 400 WORDS)
Srinivasan
B D
BD
Department of Ophthalmology, Columbia University, New York, NY 10032.
Kulkarni
P S
PS
D000305:Adrenal Cortex Hormones / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors*; D004537:Eicosanoic Acids / Q000276:immunology; D005128:Eye Diseases / Q000188:drug therapy*; D007249:Inflammation / Q000188:drug therapy; D008084:Lipoxygenase / Q000096:biosynthesis; D008269:Macular Edema / Q000188:drug therapy; D008916:Miotics / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D011680:Pupil / Q000187:drug effects; D011817:Rabbits
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D004537:Eicosanoic Acids; D008916:Miotics; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases