The putative role of prostaglandins in surgical miosis.
Most clinical studies demonstrate a small (0.5-1.0 mm) but significant reduction of surgical miosis by cyclooxygenase inhibitors (COIs), such as indomethacin, flurbiprofen, or suprofen. However, other studies failed to show significant inhibition by some of these agents. While this inhibition may provide a clinically useful advantage in some cases, it does not help us clarify the mediators and mechanism of the miotic response. The inhibitory effect of high doses of COIs on surgical miosis has generally been explained on the basis of inhibition of PG synthesis. However, COIs do not selectively inhibit the synthesis of PGs; they inhibit the synthesis of all cyclooxygenase products, including prostacyclin and thromboxanes. The reduction of the miotic response could also have resulted, in part, from inhibition of the lipoxygenase pathway of arachidonic acid metabolism. The effect of COIs on unrelated biochemical processes that influence the contractile responses of the iris sphincter may also have contributed to the inhibition of surgically induced miosis. In short, the mechanism by which COIs reduce miosis remains unidentified. If one assumes that PGs are the only mediators of this miosis, one must also assume that failure of COIs to block surgical miosis is due to incomplete inhibition of cyclooxygenase activity in the involved ocular tissues, even though the COIs are applied repeatedly to the eye prior to surgery. However, a more likely explanation is that other mediators are involved in the miotic response, especially since no PG has yet been shown to produce a dose-dependent miotic response leading to full sphincter contraction in any primate (see Miranda and Bito, 1989). While acetylcholine is the best-established agonist of iris sphincter contraction, surgical miosis occurs even after pretreatment with high doses of potent anti-cholinergic agents. This atropine-resistant component of the surgically induced miosis may be mediated by a number of autocoids. Several autacoids, other than PGs, have been shown to be potent miotic agents in some animals. LTC4 and LTD4, which are potent miotics in cats, have not yet been investigated for their possible role in surgical miosis in primates. Several neuropeptides are potent miotics in rabbits, although none of them has yet been found to have similar effects on human irides. Because sensory neuronal involvement in trauma-induced miosis has been demonstrated in many species, including humans (see Stjernschantz and Bito, 1989; also Unger, 1989), a search for a neuropeptide that has miotic properties in humans should continue. Much more work must be done before the mechanism of surgical miosis can be clarified.(ABSTRACT TRUNCATED AT 400 WORDS)
Camras
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CB
Department of Ophthalmology, Mt. Sinai School of Medicine, New York, NY 10029.
Miranda
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OC
D000818:Animals; D002387:Cataract Extraction; D002924:Ciliary Body / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors; D005480:Flurbiprofen / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007498:Iris / Q000378:metabolism; D013508:Ophthalmologic Surgical Procedures; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000502:physiology*; D011680:Pupil / Q000187:drug effects*; D011817:Rabbits
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D005480:Flurbiprofen; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin