Effects of morphine on corneal sensitivity and epithelial wound healing: implications for topical ophthalmic analgesia.

Studies were conducted to examine the analgesic and toxic effects of topical morphine on corneal abrasion. For the toxicity study, rabbits were anaesthetized and epithelial cells were removed from the cornea and limbus. Animals were randomised and treated topically as follows: (1) saline (control); (2) morphine sulphate (MS, 0.5%); and (3) proxymetacaine hydrochloride (proparacaine) (PH, 0.5%). Two drops of the solution were instilled in the eyes at 4 hour intervals for 6 consecutive days and the progression of corneal wound healing was assessed. Results showed that repeated topical MS had no adverse effects on corneal wound closure. The rates of wound healing were similar in both saline and MS treated groups. Eyes treated with MS showed wound closure in a symmetrical fashion starting on day 2 following abrasion. The progression of epithelial wound healing was completed by day 4 in one eye, by day 5 in three eyes, and by day 7 in five eyes. In contrast, repeated topical PH application delayed corneal wound closure. Eyes treated with PH showed signs of corneal wound closure on the third day, but only two eyes out of six had completed wound closure by the eighth day after corneal abrasion. In a subsequent masked study, the analgesic efficacy of topical MS was assessed in seven patients with unilateral corneal abrasion. In all cases, a baseline response was first established. Subsequently, saline was instilled in both eyes and the patient's corneal response to pain pressure was determined 10 and 20 minutes later. Finally, MS was applied and the analgesic effect on the cornea was assessed. Results showed that saline had no effect compared with the baseline response. In contrast, MS showed an analgesic effect as early as 10 minutes after application in the eye with corneal abrasion. MS showed an analgesic efficacy of 4.3-fold and 5.5-fold greater than the baseline or saline on the eye with corneal abrasion. However, MS had no analgesic effect on the intact corneal. Collectively, these data indicate that opioids do have a desirable analgesic property with out irritating or causing any adverse effect on ocular structures.