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Three organizations in the U.S.A. ask health care providers to report adverse effects of drugs in their patients: The Food and Drug Administration; United States Pharmacopoeia; and the National Registry of Drug Induced Ocular Side Effects and Drug Interactions. In a comprehensive Table, the characteristics and procedures of these three organizations are summarized.

A 20-year-old woman developed severe orthostatic hypotension after attempting suicide by ingesting the rodenticide, Vacor. Oral ergotamine tartrate, 6 mg a day, was useful in treating the orthostatic hypotension. However, a bilateral toxic retinal vasculopathy, consisting of a severe generalized vasoconstriction and mild macular edema, occurred within three weeks. Additional findings were an extinguished electroretinogram and a reduced dark-adaptation retinal sensitivity; because we performed these two tests after instituting ergotamine therapy we do not know whether to attribute their abnormal results to Vacor toxicity, ergotamine toxicity, or a combination of the two.

We measured the ocular positions of conscious and anesthetized subjects from photographs. We obtained the conscious basic horizontal deviation by using the cover-uncover test. Intravenously administered succinyldicholine chloride, 2 mg/kg of body weight, returned the eyes of 15 anesthetized volunteers to positions that agreed well with those of their conscious horizontal basic deviations in the primary position. The mean ratio (+/- S.E.) calculated by dividing the horizontal interlimbal distance 90 seconds after drug injection by that of the same subject's horizontal interlimbal conscious basic deviation was 0.99 +/- 0.01. This result supported the theory that the multiply innervated (en grappe) extraocular muscle fibers were responsible for the basic deviation. Macaca nemestrina monkeys and baboons proved to be unsuitable primate models for the human succinyldicholine response. In humans, the drug-induced ocular position was often vertically above or below the primary position. The associated horizontal deviation appeared to follow the physiologic V pattern, being more divergent if the eyes were rotated up and more convergent if the eyes were rotated down. In one third of the subjects this vertical deviation resulted in drug-induced horizontal interlimbal distances that disagreed by more than 5% with those of the conscious basic deviation in the primary position. This effect makes succinyldicholine of little value for making quantitative estimates of the amount of ocular muscle surgery to be performed during strabismus correction procedures. We injected succinyldicholine at the conclusion of strabismus surgery in eight subjects to determine if the drug-induced ocular positions would predict the postoperative results. The muscles operated on responded as though temporarily paretic. The drug-induced ocular positions bore no resemblance to the postoperative results.

Seven subjects with intracranial pathologic abnormalities received bilateral instillations of echothiophate. Six had unilateral third (oculomotor) nerve paralysis; one had unilateral third nerve paresis. All 14 eyes became miotic. Miosis was greater in the defective eye in three subjects, greater in the normal eye in two subjects, and equal in two subjects. The neurons originating in the ciliary ganglion and terminating on the sphincter pupillae muscle may exhibit spontaneous activity. Echothiophate, by preventing acetylcholine hydrolysis, may have allowed this transmitter to accumulate and to produce miosis. The amount of maximal miosis in the abnormal eye after bilateral instillation of echothiophate drops may vary from that in the normal eye. The causes of this variation include denervation supersensitivity of the sphincter pupillae muscle, partial paresis of the dilator pupillae muscle, and increased drug penetration in the abnormal eye.

Although oral drug bioinequivalence has been attributed to a number of causes (excipients, dosage form, variation in dissolution time, and aging) less is known about bioavailability problems of topical medications in ophthalmology. Factors that can alter drug absorption from solutions (pH, partition coefficient, container impurities, contact time, etc.) are noted, and cases in which bioavailability problems should be considered as causes of therapeutic failure are discussed. Various attitudes representing pharmaceutical companies, the federal government, pharmacists, consumers and physicians toward the related problems of bioinequivalence and generic prescribing are examined. Techniques for in vivo and in vitro drug testing and for establishing uniform conditions of drug manufacture and storage can contribute to identification and minimization of bioavailability problems. A rational program based on a combination of such techniques could, ultimately, lead to establishment of the terms "generic equivalency" and "therapeutic equivalency" as synonymous.

In a study of 27 cases of surgery for cataract extraction, mepivacaine 2% with hyaluronidase was found to shorten the induction times of facial nerve and retrobulbar blocks when compared to injections of mepivacaine 2% alone. The mean induction time of facial nerve blocks with hyaluronidase was 1.3 +/- 0.4 minutes. This was significantly (P less than .01) shorter than the mean induction time without hyaluronidase, 2.9 +/- 1.8 minutes. The use of hyaluronidase significantly (P less than .02) shortened the induction time of retrobulbar blocks. The median induction time with hyaluronidase was three minutes, whereas that without hyaluronidase was ten minutes. However, the use of hyaluronidase did not significantly (.25 less than P less than .50) alter the success rate of retrobulbar blocks.

It is generally accepted that postoperatively radiographic examinations be limited to the area of pathology. The patient presented here complained of visual difficulties two years after transphenoidal removal of a pituitary prolactinoma. His endocrinologist ordered what he believed to be the appropriate computed tomography study and the neuroradiologist did not correctly interpret the new finding of dilated ventricles. Subsequently, a second primary tumor was discovered, a pineal gland sarcoma. The patient had refused radiotherapy after removal of his prolactinoma. Had he not, his second tumor would probably have been attributed to radiation. It is interesting to speculate whether radiation scatter from treatment of the prolactinoma would have prevented the pineal gland sarcoma.