4. Reduction of ocular tension by stimulation of osmosis, of lymphagog activity, of absorption of edema, and of capillary contractility, and by decreasing affinity of ocular colloids for water.
1. The Myotics. Of these, eserin (physostigmin) and pilocarpin, with their respective salts, the sulphate and the salicylate in the first instance, and the hydrochlorid and the nitrate in the second, are well established in favor and efficiency. Personally, it has always seemed to me that the salicylate of eserin is preferable to the sulphate, but I have not persuaded myself that the nitrate of pilocarpin possesses material advantages over the hydrochlorid, although some authors prefer it. With arecalin, the alkaloid of the Betel nut, I have no experience, nor have I used its mixture with eserin, recommended by Merck as more potent than either of the drugs in separate solution.
The substance isophysostigmin, found with eserin in Calabar bean, according to Ogiu, exceeds in its myotic activity the sulphate of eserin, i. e., 1/80 of a grain of the drug is equal to 1/60 of a grain of the sulphate of eserin, but it is certainly not less irritating than physostigmin, and according to Stephenson's researches, is more so, and in this sense has no superiority over the usual alkaloid. In general terms, it may be said that the time has not arrived to make a preachment "on the passing of eserin and pilocarpin."
Physiologic Action. Concerning the ocular, physiologic action of the two chief alkaloids respectively of Calabar Bean and of Jaborandi, there still exists difference of opinion. It has always been easy to attribute the myotic action of these drugs, or at least, of eserin, to their stimulant action on the peripheral ends of the oculo-motor, thus causing sphincter contraction, and to a depressing action on the sympathetic fibers, thus causing removal of the action of the dilatator of the iris. But complete experimental proof of such action is wanting, and it is probable that myosis follows a direct stimulation of the sphincter muscle fibers, aided, perhaps, by contraction of the iris vessels, although the last named effect is denied by so competent an authority as Hobart Hare.
Exactly how the myotics reduce intra-ocular tension is not definitely proven. Usually it is taught that because of the myosis the base of the iris wedged in the angle of the anterior chamber is loosened and withdrawn, precisely as a fold in a coat is straightened by a tug on the fabric beneath it. Experiments, however, for example, by E. E. Henderson, have shown that the rate of filtration in an eye with artificially raised pressure is considerably larger when it is under the influence of eserin than it is when under the influence of atropin; that is by the contraction of the pupil the iris-surface filtration is increased and consequently the pressure is reduced. We all know that Thomas Henderson maintains that the results of iridectomy are beneficial because the raw edges of the coloboma, which do not cicatrize, permit access of the aqueous to the iris veins, and that myotics, inasmuch as they contract the pupil, open the iris crypts and therefore act, less efficiently, perhaps, but act none the less like an iridectomy. The normal intra-ocular pressure is uninfluenced by myotics because this pressure represents the lowest circulatory pressure in the eye, and further contact between aqueous and veins cannot reduce it below this level, another point which is made by Thomas Henderson in support of his contention.
The clinical fact remains that either by mechanical means, as it were, in the liberation of a plugged filtering angle, or by the increasing of iris-surface filtration, the myotics markedly reduce the abnormal intra-ocular pressure.
Methods of Administration and Indications. With the methods of administration of the myotics we are all so familiar that time need not be wasted in their reiteration, except to refer to a few practical points. In acute glaucoma, and every one knows that in this disease their action is often prompt and sometimes curative, eserin in a strength of one to four grains to the ounce may be instilled with sufficient frequency to establish myosis, and its action in this respect is enhanced if the congestion of the eye is lowered by measures to which I shall refer later. There is a good deal of clinical evidence to indicate that in this type of glaucoma, as well as in the so-called sub-acute varieties, myotic activity is increased by a mixture of pilocarpin and eserin in the same solution, exactly as a mixture of arecalin and eserin is more potent than either of the drugs in separate solution.
Prior to the happy advent of technically correctly placed filtering cicatrices, a large number of surgeons depended almost exclusively on the use of myotics in so-called simple, chronic or non-inflammatory glaucoma. This is not the place to introduce a discussion of the comparative value of iridectomy and myotic treatment in simple glaucoma as based upon statistical records. We must wait now for a sufficient period of time and then compare the value of myotic treatment with that of operations by means of which satisfactory filtration is produced. We are somewhat in the position that general surgeons occupied when aseptic methods first became prevalent. We do not usually compare the statistics of early aseptic days with those of the pre-antiseptic period, and I do not think we ought to compare the statistics of myotic treatment with ordinary iridectomy any longer, but that we should wait until we can make a comparison between the results of prolonged myosis and those of an improved modern technic which establishes a permanent filtration. In the meantime the patients who will not or cannot submit to operation must be reckoned with. Doubtless many patients with chronic glaucoma can be satisfactorily managed with myotic treatment, although personally I have always advocated operation when this could be performed, but it cannot always be performed. This rule should guide us, namely, to begin with a comparatively weak solution of the selected drug, for example, as Posey has advocated a tenth of a grain of salicylate of eserin to the ounce, and the strength gradually increased so that at the end of some months the patient is using a solution 1 grain to the ounce; or if the pilocarpin is preferred, solutions in double these strengths. It is my own belief, and that of many who have studied this subject, that if, without eserin irritation, a myosis can be maintained, and if the treatment can be begun early enough, the chances of preserving vision and the field of vision are good. I believe that the two most important instillations during the twenty-four hours of the number necessary to maintain this myosis are on retiring and if possible in the very early morning, some time between two and four o'clock. Most patients can be taught to wake themselves at the proper period of time, and are little inconvenienced by this disturbance of their sleep. I believe that eserin irritation is most successfully avoided, not by preparations of the myotics in combination with the antiseptics, for example, tricresol, which has been so much advocated, but by ordering very small quantities of the solution, insisting that it shall be frequently renewed and sterilized at each preparation, and that a half an hour after its instillation, during the day time at least, the eye shall be thoroughly flushed with some mild antiseptic solution, for example, boric acid and sodium chlorid. Whether the action of the eserin on the choroidal circulation, which is maintained by Wahlfours, aids in this favorable action of the myotics remains to be proved. It has been maintained by this author and by others who have followed him.
The great trouble with myotic treatment is not its lack of efficiency, but the difficulty of carrying it out successfully on ambulant patients, even in the better walks of life. It is hard successfully to maintain in a patient with chronic glaucoma what I may call an eserin life, just as it is hard to maintain in a person with an enlarged prostate a catheter life and escape infection, resulting, if it occurs, in the one instance in a difficult and stubborn conjunctivitis, and in the other in a cystitis. Still, we are obliged to use myotics, and the way to employ them to the patients' best advantage, I have ventured to repeat in spite of the universal familiarity with the methods. Perhaps we may reach that happy day when, especially with improved tonometric methods, increased skill in measuring the rate of filtration and better instruments for determining the light sense, we can anticipate the advent of glaucoma and get ahead of the ocular and visual deterioration which increased tension produces, by performing preventive operations which shall aid nature's filtration channels in the establishment of an artificial one. But increased tension is not the whole story of glaucoma, and a filtering cicatrix is not the last word in surgical therapeutics, and there is much to learn.
2. Reduction of tension by means of various mechanical measures, notably massage, and by means of electricity and diathermy. Massage is of ancient lineage. In general terms, in so far as ocular massage is concerned, it may be applied to the eye with the finger tips (ordinary massage), by means of various instruments (vibration massage), and with the help of certain suction cups (suction massage, which is indeed a form of vibratory massage). Many authors are satisfied with their results without the employment of any instrument, and prefer simple massage with the tip of the finger to any form of the instrumental variety, to quote the words of Casey Wood. At one time in my career I experimented very extensively with massage, not alone for the purpose of reducing intra-ocular tension, but in various diseases of the lid and cornea, and taught a trained nurse, who herself had a nebulous cornea, to make what I may call a specialty of this particular therapeutic procedure. She became exceedingly skillful and was quite faithful. We believed that the best results were obtained in a seance of two or three minutes, the finger tip being used over the lid, and the surface of the cornea lubricated with a drop of pure olive oil, although in glaucoma the addition of the oil is not necessary. Four movements were utilized, the first a stroking movement in lines radiating from the central pressure, very much as the spokes of a wheel radiate from the hub, second a circular movement, third a pressure movement, a little dipping motion, so that the cornea was slightly depressed, and finally, a gentle tapping movement, precisely the same, except that it was a diminutive one, as the tapping movement that the Swedish masseur makes. Usually each movement occupied from a half to one minute, according to the results desired. I agree with Casey Wood that such a technic furnishes just as good results as any one with the aid of an instrument.