respiration, the accumulation of venous blood causes irritation of the dilating centre and widens the pupil. Dilatation of the pupil during the administration of anaesthetics is therefore to be regarded as a sign of failing respiration.

The contraction caused by morphine is also central and probably due to a similar cause.

It is possible that the local application of drugs to the eyes may have an action on the pupil due merely to their effect as irritants, and independent of any special action on the iris, for E. H. Weber1 found that local irritation at the margin of the cornea causes partial dilatation. Irritation in the middle of the cornea causes rather contraction of the pupil. Localized irritation at the margin of the iris may cause dilatation at that part.

The reason why muscarine has been found by Ringer and Morshead to dilate the pupil when applied locally is probably that the solution they used was very irritating, either from its strength or for some other reason, while Schmiedeberg and Harnack found it to contract the pupil both when given internally and applied locally.

The contraction of the pupil noticed by Rossbach in rabbits immediately after the application of atropine, may also have been due to local irritation. The occurrence of dilatation in one case and of contraction in the other may possibly have been due to the solution being dropped into the eye in a different way in the two cases.

The most important local mydriatics and myotics are atropine and physostigmine (eserine).

When a solution of atropine is dropped into the eye, the pupil dilates and the ciliary muscle becomes paralyzed, so that the accommodation for near objects is no longer possible, and the eye remains focused for distant objects. When a solution of physostigmine is dropped into the eye, the pupil contracts and the ciliary muscle becomes spasmodically contracted, so that the eye is accommodated for near objects.

It is very difficult to explain their mode of action satisfactorily, and authorities are by no means agreed regarding it. That the action is local is shown by the fact that when either atropine or physostigmine is applied to one eye its action is limited to it and the other remains unaffected. If care be taken to limit the application of a solution of atropine to one side of the margin of the cornea, local dilatation of the corresponding part of the pupil may be produced.

Dilatation of the pupil may be due to paralysis of the sphincter or excessive action of the dilator.

Paralysis of the sphincter may be due to (1) imperfect action or paralysis of the oculo-motor centre in the corpora quadrigemina, (2) to paralysis of the ends of the third nerve in the sphincter iridis, or (3) to the action of the drug upon the muscular fibres of the sphincter itself, or to one other or all of those together.

Along with the factors just mentioned might be associated excessive contraction of the dilator muscles, which may be due (1) to stimulation

1 Quoted by Landois, Physiologie, 1880, p. 799.

of the sympathetic centre in the medulla, (2) of the ends of the sympathetic in the dilator muscle, or (3) stimulation of the dilator muscle itself.

Excluding for the present the question of excessive action of the dilator muscle and confining ourselves to the causes of paralysis, we see that paralysis of the cerebral oculo-motor centre as a factor in dilatation of the pupil by atropine is excluded by the local action of the drug, and also by the experiments of Bernard and others, which show that dilatation occurs from the local action of atropine, when the ciliary ganglion is extirpated and all the nerves of the eye with the exception of the optic have been divided. We can now limit its action either to paralysis of the ends of the oculo-motor nerve, or paralysis of the muscular fibres of the sphincter.

That the ends of the oculo-motor nerve in the sphincter iridis are paralyzed is shown by the experiment that when the pupil is under the full action of atropine, irritation of the third nerve will not produce any contraction in it, although the sphincter will still contract when stimulated directly.

Here also we find the same relation between the action of atropine on nerves supplying striated and non-striated muscle that we have already noticed in the case of the oesophagus, for in most animals the iris consists of unstriated muscular fibre, and atropine causes dilatation; but in birds the iris consists of striated muscular fibre, and atropine causes no dilatation. Paralysis of the ends of the oculo-motor nerve in the iris itself may be looked upon as one of the factors in dilatation by atropine, and similar paralysis of the fibres supplying the ciliary muscle may be regarded as the cause of loss of accommodation.

In addition to this, however, when the dose of atropine is large, the muscular fibres of the sphincter themselves become paralyzed, and fail to contract even when directly irritated.

The question now arises whether in addition to paralysis of the oculomotor nerve there is not also excessive action of the dilator. That such action of the dilator is actually present appears to be shown by the following fact, viz., that the dilatation caused by atropine does not appear to be merely passive, but occurs with such force as to tear the iris away from the lens, and break down adhesions which may have formed between them. This conclusion has been considered to be supported also by the facts: (a) That when the oculo-motor nerve is divided the pupil does not dilate nearly to the same extent as it does from the application of atropine. This is shown both by a comparison of measurements of the eye under the two conditions and by the observation that after the nerves have been divided and partial dilatation produced atropine causes the pupil to dilate still more. (b) When the pupil is dilated by atropine, section of the sympathetic in the neck lessens the dilatation.

We may consider, then, with tolerable certainty, that dilatation caused by atropine is due to increased action of the dilator as well as diminished action of the sphincter muscles of the iris.

Contraction of the pupil may be due to excessive action of the sphincter, or paralysis of the dilator. That the contraction caused by physostigmine is not due to paralysis of the dilator is shown by the pupil

dilating somewhat when shaded, even when the drug is exerting a wellmarked action. Excessive action of the sphincter must therefore be regarded as the cause of the myosis. Such action may be due to (1) stimulation of the oculo-motor cerebral centre, (2) of the ends of the oculo-motor nerve in the sphincter, or (3) to increased action of the muscular fibres in the sphincter from the direct effect of the drug upon them. The local action of physostigmine upon the eye excludes the cerebral centre, and leaves for our consideration stimulation of the ends of the nerves and of the muscular fibres themselves.

These two structures seem to be specially affected by different drugsso that local myotics may be divided into two classes

1st. Those which act upon the peripheral ends of the oculo-motor

nerve.

2d. Those which affect the muscular fibre of the iris.

The first class includes muscarine, pilocarpine, and nicotine. Physostigmine belongs to the second.

Muscarine, pilocarpine, and nicotine, when applied to the eye, cause contraction of the pupil and spasm of accommodation. Atropine, as we have already seen, not only paralyzes the ends of the oculo-motor nerve, which these drugs stimulate, but has also an action on the muscular fibre itself. Its subsequent application will therefore remove the effect of these drugs, and they will not act after atropine has been applied first. As physostigmine stimulates the muscular fibre itself, it will cause contraction in an eye which is dilated by atropine.

The contraction produced by muscarine in the eye of the cat is so great as to reduce the pupil to a mere slit, and is much greater than that caused by the physostigmine, for muscarine acting only on the ends of the oculo-motor produces spasm in the sphincter without affecting the dilator, while physostigmine acting on the muscular fibres stimulates those of the dilator as well as the sphincter, and thus renders the contraction less complete.1

It has already been pointed out, however, that the action of atropine is not confined to the ends of the oculo-motor nerve, but affects the muscular fibre itself, and thus it will counteract the effect of physostigmine, which it would not do if it acted only on the nerves.

Atropine consists of the combination of a base, tropine, with tropic acid. Tropine itself has no mydriatic action, but when an atom of hydrogen in it is displaced by an acid residue it acquires this action. A number of combinations of tropine with different acids have been artificially prepared by Ladenberg, who terms them tropeïnes. Amongst these are homatropine, in which the tropine is combined with oxytoluylic acid, and also benzoyl-tropine. Atropine appears to be identical with daturine. Hyoscyamine is also a combination of tropine with tropic acid, but it appears to be only isomeric with and not identical with atropine, though it appears to be identical with duboisine.

Action of Drugs on accommodation.-The accommodation of the eye depends upon the ciliary muscle. When the eye is at rest the

1 Schmiedeberg, Arzneimittellehre, p. 71.

lens is flattened by the elastic tension of the zonule of Zinn. During accommodation for near objects the ciliary muscle draws the zonule forward and allows the lens to become more convex. The ciliary muscle is innervated by the third nerve: the centre for it appears to be in the posterior part of the floor of the third ventricle. Those drugs which affect the iris, also affect the power of accommodation. Their action on the iris and on accommodation do not, however, always begin at the same time, nor have they the same duration. The action of physostigmine and atropine on accommodation usually begins after, and passes away long before, the affection of the pupil.

Action on intra-ocular pressure.-The intra-ocular pressure depends chiefly on the relation between the amount of fluid poured into the anterior chamber of the eye, and the amount which passes out in a given time. This fluid is chiefly secreted by the ciliary processes. It passes out from the anterior chamber of the eye by a number of small openings (f, Fig. 50) close to the junction of the cornea and iris into the canal of Schlemm (c, 8, Fig. 50), thence into the perichoroidal space, and out through the lymphatics.

The intra-ocular pressure may be increased by (a) more rapid secretion from the ciliary processes, or (b) interference with its outward flow from the eye, or (c) by increased quantity of blood in the vessels of the iris. It may be diminished by the contrary conditions.

More rapid secretion from the ciliary process probably takes place under nervous conditions which are not at present well known. Interference with the flow of the aqueous humor out of the anterior chamber may occur in aquo capsulitis, in which the openings from the anterior chamber into the spaces of Fontana are probably blocked by a coating of inflammatory lymph; in glaucoma where these openings are blocked by the iris being pressed forward against them as in Fig. 50, and in iritis

FIG. 50.-This diagram (which I owe to the kindness of Mr. J. Tweedy) represents a section through the corneo-scleral region, ciliary body and iris, of a healthy eye (left side), and of a glaucomatous eye (right side): cornea; s, sclerotica; i, iris; f, spaces of Fontana; c s, canal of Schlemm. In the glaucomatous eye the ciliary body is atrophied, and the iris lies against the cornea preventing the escape of fluids through the spaces of Fontana and canal of Schlemm.

where the iris is much congested and the openings in it perhaps occluded by lymph. The secretion is probably diminished by the action of atropine. The outward flow through the spaces of Fontana is increased by Calabar bean, which, causing contraction of the circular fibres, flattens the arch of the iris and draws it away from the cornea so as to widen the angle between the cornea and iris, and aid the passage of fluid into the space of Fontana.1

1 J. Tweedy, Practitioner, Nov., 1883, vol. xxxi., p. 321.

There are few or no experiments on the tension in the vitreous humor of the eye, and by the term intra-ocular tension is usually intended the pressure in the aqueous humor. This is usually ascertained by simply pressing the finger upon the eye and observing whether it is harder or softer than usual, or by pressing upon it with an ivory point attached to a registering spring, and noticing the pressure required to produce an indentation. These methods of experiment are very inaccurate, and it is much more exactly ascertained by passing a small trocar into the anterior chamber and connecting it with a manometer. The results of experiments even by this method are not entirely in accordance.

The most recent ones by Graser1 appear to show that the tension depends to a great extent upon the height of the blood-pressure generally: contraction of the pupil diminishes, and dilatation increases the intra

ocular tension.

Atropine in doses sufficient to dilate the pupil increases the tension. This action of atropine and its allies in increasing the tension makes them dangerous in cases of glaucoma, and where this disease has been impending it has been at once brought on by the use of atropine or duboisine. Eserine causes temporary increase at first, but after contraction of the pupil comes on, the tension is diminished. Eserine is therefore useful in glaucoma.

Uses of Mydriatics and Myotics.-Belladonna is employed locally for its sedative action to relieve pain and irritation in the conjunctiva.

Mydriatics and myotics are used not only for their action upon the pupil but for their action upon accommodation and intra-ocular pressure.

Mydriatics are employed to dilate the pupil for the purpose of facilitating ophthalmic examination, assisting the detection of cataract commencing in the periphery of the lens, or allowing the patient to see round the margin of a cataract when this is central in position, and would obstruct the vision with a pupil of normal size. They are used to prevent prolapse of the iris, or to restore it to its normal position when already prolapsed in cases of perforating ulcer or mechanical lesion of the cornea. They are employed in iritis, to afford rest to the inflamed tissues of the eye, and to keep the iris as far as possible off the surface of the lens and prevent adhesions of its posterior surface to the anterior surface of the lens.

Myotics are used to contract the pupil in cases of photophobia, or to counteract the effect of mydriatics which have been previously employed. They are used also to counteract deficiency in tension of the ciliary muscles, as in paralysis of accommodation consequent on diphtheria, asthenopia, and hemeralopia.

Mydriatics and myotics may be employed alternately in order to ascertain the presence of any adhesions of the iris, and to break them up if present.

Mydriatics are employed to paralyze the ciliary muscle, and thus destroy the power of accommodation in order to test the condition of the

1 Graser, Archiv f. exp. Path. u. Pharm., Bd. xvii., Heft 5.