728 NOTES, CASES, INSTRUMENTS

can be prepared at the same t ime; other-wise, the nosepiece of the frame can be cut with a separating disc and both halves of the glasses individually prepared and then reunited by soldering the nosepiece.

Fur ther adaptations for and changes in the appliances may suggest themselves in individual cases. T o date in our cases they have proved to be most satisfactory.

AAF Regional Station Hospital.

S Y N T R O P A N AS A M Y D R J A T I C *

W E R N E R BAB, M.D. . . San Francisco, California

My last report1 on syntropan in 1942 dealt with several attempts that were made to exclude the burning sensation of syntropan solutions to be used for diagnostic mydriasis. Syntropan (Hoff-mann-LaRoche) is the phosphate salt of 3 diethylamine, 2.2 dimethylpropanol tropic acid ester. Its main effect is para-sympathetic, and its internal uses are chiefly the same as those of atropine. Its advantages as a mydriatic were then de-scribed : the rapid effect; the short dura-tion ; no general dangers nor discomforts; no local dangers, as damaging the corneal epithelium, or increasing the intraocular pressure; no delay in returning to work for the patient.

These advantages have been confirmed during the last three years. For lack of time, many patients did not want to wait in the office for dilation for an hour or two, and were inconvenienced by being unable to go back to work immediately after the examination. Strictly speaking, syntropan never irritated the eye, but the burning sensation often caused a flow of tears that delayed the effect of the mydri-atic by washing away part of the instilled drops.

Recent developments. The following

* From the Department of Ophthalmology, Mount Zion Hospital.

observations result from experiences with more than 300 cases. The exact measure-ments (ruler or strabometer) of pupillary size have been regularly taken since 1942. All solutions were buffered according to the prescriptions of Gifford.2 A solution that was buffered and made isotonic with tears at the same time promised to be most satisfactory. In 1943, a solution was pre-pared* that was based on a recent re-search of Arrigoni and Fischer3 who postulated that ophthalmologic solutions should be isotonic with tears, and that the pFf should be adjusted within narrow limits of the lacrimal fluid, if a nonirri-tating collyrium was to be prepared ( p i I of tears about 7.4). But these authors stated that a solution within the p H range of 6.5 to 7.8 was nonirritating, if the col-lyrium was isotonic. The freezing point of tears was staled to be equivalent to that of a 1-percent solution of sodium chlo-ride, which lowered the freezing point by 0.8°C. Accordingly a 4-percent syntropan solution (sol. no. 7) isotonic with tears was prepared. The freezing-point depres-sion was 0.822° C , close to the require-ment. But it was not possible, we were in-formed, to obtain a stable syntropan solu-tion with a high p H . The p H of this solution, therefore, was 4.33. Even this low figure showed a very slight diminu-tion when the solution was allowed to stand for a month or more. A local phar-maceutical laboratory also stated that it was impossible to have a stable syntropan solution prepared that had the necessary high p H . As this solution was "burning" again, as was anticipated, I returned to previous efforts to make syntropan non-burning, by incorporating an anesthetic.

A new 4-percent solution (sol. no. 8 ) , isotonic with tears and with a p H of 4,

t William T. Strauss, M.D., of the medical department of Hoffmann-LaRoche, was helpful in having this and several other syntropan solu-tions prepared. For their interest in these tests I wish to thank Dr. Strauss and his co-workers.

NOTES, CASES, INSTRUMENTS 729

that contained 1-percent holocaine, was prepared and used for half a year. Only the first drop burned, the following drops did not. Mydriasis was satisfactory after 25 to 35 minutes. In dark-complexioned persons its effect was usually delayed for 10 to 15 minutes. For slitlamp examina-tion one or two more drops had to be given, and the period of waiting was slightly extended. But the dilatation was never such that the pupil did not contract with the strong light of the slitlamp (retained light reaction of the pupil with the 4-percent solution).

For these reasons the use of a stronger and more efficient solution was taken under consideration, also the return to a higher pH, if possible. The idea of mak-ing the solution isotonic with tears was abandoned to stress the higher pH. A local pharmacy prepared a 6-percent so-lution (sol. no. 9) , and with a pl l of 6.6. This solution was more satisfactory. One drop of an anesthetic was instilled before the solution was used, but this was soon abandoned as unnecessary. The desired effect, except in dark-complexioned per-sons, was faster than with the 4- or 5-percent solution. After two months, the patients began to complain again about burning. Since I knew that the high pH of this solution was dangerous to its stability, its pH was examined and found to have dropped from 6.6 to 6.2. Although this change of 0.4 was small, the figure of 6.2 was lower than 6.5, the limit al-lowed by Arrigoni and Fischer.3

Recent findings. A new solution was prepared again with a pH of 6.6 and in a 6-percent strength (sol. no. 10). This has now been used for four months and has not lost its stability so far. Its pH will probably go down after a time, as has been the case with all previous so-lutions. With this restriction the findings are now: (1) A 6-percent solution is bet-ter than the previously used weaker solu-tions. The use of the slitlamp is possible

because the light reaction is negligible. (2) Retinoscopy can now be done to an extent that was previously never consid-ered. The amount of the cycloplegic effect varied between 1 and 2 diopters after one-half to one hour. If there is a doubt about the retinoscopic values, the addition of one more drop of syntropan and waiting a few more minutes make the results more dependable. Previous reports that claimed that syntropan would not affect the accommodation are therefore not ex-act. Concentrations of 1 or 2 percent never result in any measurable cyclo-plegia, whereas 4- and 5-percent concen-trations do. The 6-percent solutions have a definite and rapid cycloplegic effect, measurable by comparing the lens power at which 14/14 A.M.A. rating print is easily read at near distance. (3) Even the use of five drops of this 6-percent solu-tion had no tension-raising effect (meas-ured with a Schieitz tonometer). Since I starte'd to use syntropan (in 1934) no glaucoma has been induced by it. It was, however, never used in any case of a suspected or manifest glaucoma. After the cycloplegic properties were found, it was considered not safe enough to press the point as to the nontension-raising properties of syntropan. It probably de-pends on the concentration whether this effect will be present or not.

Present procedure, (a) Usually a drop of an anesthetic is instilled first, (b) Three to five drops of 6-percent syntro-pan are instilled at 3- to 5-minute inter-vals. Each case is handled individually ac-cording to the time available, the rapidity of dilation, or the needs (diagnostic myd-riasis only, or slitlamp examination also). (c) Routinely, one or two drops of 2-per-cent pilocarpine are instilled before the patient leaves. This brings the pupil back to its original size within 20 minutes. Fresh solutions burn less than solutions allowed to stand longer. Because of the burning of older solutions, more tearing

730 NOTES, CASES, INSTRUMENTS

results, and with it more syntropan es-capes. Thus the loss of time through intial instillation of an anesthetic is com-pensated by the more intense effect of the syntropan without excessive lacri-mation.

Details of the mydriasis. If the interval of three drops given is three minutes each, the mydriatic effect is faster than when the interval is five minutes. The av-erage dilatation following instillation of the 6-percent solution (three drops at in-tervals of three minutes) is a pupillary di-ameter of 7 to 8 mm. after 25 to 30 minutes. After 15 minutes the pupil is usually not wider than 4 mm.; 35 to 50 minutes after the first drop, the pupil is dilated 8 to 9 mm. in size.

Syncrgistic effect of neo-synephrine. When the 2.5-percent ophthalmologic so-lution of neo-synephrine was introduced, I tried it for diagnostic dilatation. The complaints about burning reminded me of my experiences with syntropan. There-fore, an initial drop of an anesthetic had to be instilled. It had been recommended for synergistic action combined with a cycloplegic. Although it was claimed that the adrenalin-like drugs affect the accom-modation too, there was never any proof of it in my experience. There was no cy-cloplegic effect from neo-synephrine alone in the doses and concentration I used. But as 6-percent syntropan had such an effect, both combined induced both an excellent mydriasis and a certain amount of cyclo-plegic effect.

The procedure with the combined use

of syntropan and neo-synephrine is now as follows: (a) One initial drop of an anesthetic, (b) After three minutes one drop of neo-synephrine. (c) Continua-tion with syntropan as described above. In dark-complexioned persons, or if the desired effect of a rapid mydriasis does not take place, each following drop of syntropan is accompanied by one drop of neo-synephrine. The combined use of both drugs hastens the mydriasis, and makes the pupil 1 or 2 mm. larger within the same period of time that syntropan alone would accomplish.

CONCLUSIONS

To the previously mentioned advan-tages of syntropan as a mydriatic the advantage of using it for retin-oscopy in adults may be added. I have recently used stronger solutions than in previous years. The effect of syntropan was proved to be that of a real cycloplegic (which is true of all the members of the atropine group). Therefore, I am now re-luctant to recommend it further, in 6-percent concentration, as not dangerous in cases of suspected or manifest glau-coma ; in such cases it is definitely contra-indicated.

Syntropan is, therefore, an excellent mydriatic. It is recommended that the solutions be renewed from time to time to avoid the change in the value of the pH and the burning sensation connected with this change.

350 Post Street (8).

REFERENCES 1 Bab, W. Eye, Ear, Nose and Throat Monthly, 1942, April. * Gifford, S. R. A handbook of ocular therapeutics. Ed. 3, Philadelphia, 1942. * Arrigoni and Fischer. Amer. Jour, of Pharmacy, 1943, v. 115, p. 23.