Drug side effects seen in clinical ophthalmology are divided into two types. The first comprises those induced by drugs administered for ocular diseases, and the second, those induced by drugs given for non-ocular diseases. Among cases of ocular side effects which were reported in scientific journals in Japan between 1956 and 1988, the most frequently seen were those induced by chemotherapeutics, steroids, several kinds of ophthalmic solutions and agents affecting central nervous system. Of recent problematic drugs with related ocular side effects, ophthalmic solution of β-blocker for cardiovascular events, cyclopentrate for psychological disturbance, anaesthetics for corneal damage, fluorescein-Na for sudden death or shock, ethambutol for optic neuropathy, oral contraceptives for disturbance of retinal circulation and steroids for cataracts and serous choroidretipathy should be paid special attention.

To detect ocular side effects induced by administered drugs as early as possible, ophthalmologists who care for the patients should always have enough knowledge about the drug and periodic examinations should be performed.

Experimental studies concerning drug toxicity on ocular tissues performed by the author's lab were briefly introduced. They were i. drug-toxicity test utilizing a cultured human conjunctival cells, ii. the influence of drug-affinity with melanin pigment which correlates with intraocular drug dynamic mode and iii. how to detect drug induced changes in the crystalline lens.

One rat of the Crj: CD strain, 16 weeks of age, was found to have eye abnormalities characterized by retinal dysplasia, typical coloboma, and retinocele possibly due to a failure of closure of the optic fissure.

Fundus examination of the eyes of the rat revealed a well delineated grayish area around the optic disk, an elongated papilla, and a hyaloid artery remnant. These findings were observed symmetrically in the fundus of both the right and the left eye. Histopathological examination revealed disorganization of the retina forming rossette, lack of rods, cones, stratum pigment layer and choroid, herniation of the retina into the sclera, and a hyaloid arterial remnant forming a loop with the retinal arterioles.

Exploratory studies have been conducted in this laboratory to induce experimentally a failure of closure of the optic fissure in rat and mouse embryos with Ochratoxin A. The induced changes were rosette formation and folding associated with derangement of the cell layer in the inner layer of the optic cup, and defect of the pigmented epithelial layer and the choroid due to irregular development of the inner and/or outer layer of the cup. These changes were mostly comparable to the changes observed in the adult Crj: CD rat.

From the above experimental results, we conclude that one of the major causes for the congenital retinal dysplasia, coloboma, and retinocele observed spontaneously in the adult rats is failure of closure of the optic fissure.

Postnatal development of the visual system in dogs was investigated by funduscopy and by electrophysiologcal and other methods during the first 6 months after birth.

Opening of the eyelids was observed between 9 and 12 days of age in beagles. A small negative wave of visual evoked potentials (VEP) was first recognized at 12 days of age. The a-wave of the electroretinogram (ERG) appeared a little later, between 16 and 19 days of age. The b-wave was recorded between 18 and 22 days of age. The amplitude of both the a- and b- waves increased rapidly between 3 and 6 weeks of age. The oscillatory potentials (OPs) were noted between 23 and 25 days of age. Characteristic OP waves, however, appeared after 6 weeks of age. The latency time in a-and b-waves shortened markedly between 3 and 4 weeks of age, and these waves exhibited a similar pattern in every examination thereafter. Measurement of the intraocular tension revealed a value of 25 mmHg at 17 days of age, this value was very close to that of adult dogs.

As accidental changes encountered during the study, retinal hemorrhage in the fundus was noticed after a single strong stimulus or repeated flash stimuli in VEP or ERG examination during the neonatral stage of 21 to 26 days of age. Such retinal hemorrhage appeared in 4 out of 19 neonates. It appeared bilaterally in one animal and unilaterally in the others. The hemorrhage was transient and the exudate in the vitreous body was absorbed 6 to 50 days later. Opacity of the cornea and neogenesis of vessels were also observed in one animal after wearing the contact lens for the ERG test.

Introduction: It has been shown that zinc pyrithione (Z-PT) causes retinal lesions in animals having a tapetum. We studied these lesions ophthalmoscopically, electroretinographically and histopathologically.

Young beagles were given orally a synthesized chymotrypsin inhibitor (FK-401) at doses of 100, 300, and 600 mg/kg/day for 35 days. Ophthalmoscopic observation revealed discoloration of the tapetum lucidum in one out of six dogs given 300 mg/kg, and in four out of eight dogs given 600 mg/kg. No changes were observed in the electroretinogram. Swelling of tapetal cells and vacuolation of arteriolae were observed in light microscopy, and enlargement of the tapetal rods was observed in electron microscopy. The tapetal discoloration induced by FK-401 at 600 mg/kg was irreversible during the 8-week recovery period. We concluded that the mechanism of tapetal discoloration was different from that produced by a zinc chelator or by beta-adrenergic blocking agents. The tapetum lucidum discoloration might be related to vacuolation of the tapetal cells. Our results suggest that retinal function could be disordered by longterm administration of FK-401. However, tapetal change was considered to be of no significance in species that do not have a tapetum lucidum.