Solid Mixtures of Homatropine and 
Cocaine as a Substitute for Atro- 
pine and Duboisine in Determining 
Refractive Krrors. 
BY 
CASEY A. WOOD, C.M., M.D. 
PATHOLOGIST TO THE ILLINOIS EYE AND BAR INFIRMARY ; 
PROFESSOR OF OPHTHALMOLOGY, CHICAGO POST- 
GRADUATE MEDICAL SCHOOL. 
[.Reprinted from “ The American Journal of Oph- 
thalmology," June, iSqi ,\ SOEID MIXTURES OF HOMATROPINE AND COCAINE 
AS A SUBSTITUTE FOR ATROPINE AND DUBOISINE 
IN DETERMINING REFRACTIVE ERRORS. 
CASEY A. WOOD, C.M., M.D., 
PATHOLOGIST TO THE ILLINOIS EYE AND EAR INFIRMARY; PROFESSOR OF OPHTHALMOLOGY', 
CHICAGO POST-GRADUATE MEDICAL SCHOOL. 
With the discomforts and drawbacks attendant upon the use of Atropine, 
employed for the determination of refractive errors, the profession is entirely 
familiar. The laity, too, are becoming more and more impatient of the ten 
days’ to two weeks’ partial blindness which often follows the instillation of 
Atropine Solutions when used for the purpose of prescribing glasses. Every 
oculist knows that many persons refuse to allow ‘ ‘ drops ’ ’ to be put into their 
eyes, mainly on account of the enforced absence from work which their use 
commonly entails. As long as Atropine is employed for the treatment of dis- 
eases that have already rendered the eyes unfit for work no complaint is raised, 
but the employment of a drug that dilates the pupil, blurs the sight for distant 
vision and makes near work out of the question, is extremely distasteful. 
More than that, there is a large percentage of the ametropic population 
urgently needing glasses who can not or will not spare the necessary time from 
business pursuits, and an almost equal number who cannot be spared, however 
willing they may themselves be to go through a “course ”of Atropine. These 
individuals have to choose between submitting to an incomplete and perfunc- 
tory examination of the optician and jewelry-store order and allowing their 
refractive errors to go uncorrected. 
I have devoted some months of the past year to experimenting with 
Mixtures of Homatropine (alkaloid, Merck) with Cocaine (alkaloid, Merck) and 
I hope to be able to show, in confirmation of Tang and Barrett’s statements,1 
that when used in a certain definite manner and dose, and with proper excipi- 
ents, this combination is a thoroughly reliable cycloplegic and quite as satis- 
factory as Atropine for determining the refractive state of ametropic eyes. 
Furthermore, the employment of this mixture is not followed by the annoying 
symptoms incident to the employment of Atropine, Duboisine, or Hyoscine. 
It accomplishes its purpose within an hour after being introduced into the con- 
junctival sac and the ciliary paralysis passes off, or may be made to pass off, 
within twelve or, at most, twenty-four hours. 
Shortly after the discovery of Homatropine, by Ladenburg* of Kiel, some 
observers (Schell,2 Pautynski,3 et al.) experimented with it, and, as a result of 
*Berichte über die Heutsch. Chem. Gesellschaft, Jan. 26, 1880. these trials, entertained the belief that it would be found to act generally as a 
substitute for Atropine. We now know that this is only partially true, and that 
Homatropine, while it possesses properties of value to the oculist, acts in many 
respects quite differently from Atropia. Pautynski, for instance, was wrong in 
thinking that, since the mydriatic and cyclopegic action of Homatropine is a 
transient one, its irritant effects upon the uveal tract are insignificant and 
that it can be used to advantage where stronger mydriatics, such as Atropine, 
are contraindicated. Stewart* and Jackson 4 have both drawn attention to the 
special irritant action exerted upon the deep structures of the eye by repeated 
applications of a watery Solution of Hydrobromate of Homatropine, and the 
former thinks this is one reason why ametropia cannot be properly estimated 
by its use. That the employment of Homatropine Hydrobromate, when used 
in aqueous solution, is unequal to the task of conquering the ciliary muscle 
has been abundantly proved by the observations and experiments of Dabney,f 
Holt,5 Oliver4 and others, notwithstanding the experiences of Risley7 (with 
Randall) and Jackson.4 Dang and Barrett, in their classical essay, have also 
shown the insufficiency of the pure alkaloids even when employed in the more 
effective castor-oil menstruum. I have myself frequently had occasion to enter- 
tain the same doubts that Holt 7 expresses in his paper as to the value of solutions, 
in water, of Homatropine and its salts (however strong the solution and how- 
ever frequent the instillations) for examining the usual run of cases requiring 
glasses. I have, for example, carefully followed Jackson’s instructions, with a 
two per cent, aqueous solution of Merck’s Homatropine instilled every ten 
minutes for an hour, and at the end of that time have found patients still pos- 
sessing some accommodative power. Watery solutions of this, as well as of 
most drugs, easily flow off through the canaliculi, and for all practical purposes 
are lost. This will account for the necessity, which Jackson insists upon, of 
frequent and continued instillations if one wishes to get satisfactory results 
from aqueous Homatropine solutions. 
More than one drop of fluid is not retained within the average sac-space. 
This one drop, in the case of the Homatropine Solution, acts as a stimulant to 
the lachrymal gland, and its secretion being added to the fluid already present, 
not only dilutes the latter, but also induces an overflow into the nose. From 
observations made upon patients during this investigation, I think I am within 
the truth in asserting that less than ten per cent, of aqueous solutions of Homa- 
tropine (or for that matter, of most other drugs) is retained for any effective 
period within the conjunctival sac. 
But there is another reason why in using Homatropine there should be a 
continuous absorption of the drug. Its action upon the iris and ciliary muscle 
is cumulative up to a certain point and it is only by taking advantage of this 
cumulative property that we can hope to overcome the ciliary activity. In this 
important particular it differs from the fiercer action of Duboisia and Atropia, 
a single drop of a two per cent, solution of either alkaloid being sufficient to 
bring about a marked and lasting ciliary paresis. TansleyJ has sought to 
prevent these unpleasant effects and this waste of material by an ingenious little 
* Philadelphia Medical News, March 3, 1886. 
f Medical Record, September 15, 18S8. 
X “ New Instruments.”—Trans. Am. Oph. Socy., 1888, p. 65. instrument, called a canaliculus compressor. I have no doubt it is an effective 
expedient, but think it would not be tolerated by many patients. 
The effect of Homatropine upon the accomodation is more lasting and more 
thorough when oleaginous menstrua and fatty excipients are employed for its 
application to the eye. This increased activity is, I feel convinced, entirely due 
to the fact that, as Green* asserts, the drug, when so exhibited, is retained 
within the conjunctival sac until absorption is complete. In Tang and Barrett’s 
experiments it was found that from one drop of a two per cent, solution of the 
alkaloid in castor oil the fullest mydriatic and cyclopegic effects were obtained 
in about sixty minutes after its instillation. This thick, fatty menstruum does 
not pass off through the puncta, like water, but diffuses itself over the whole 
conjunctival and corneal surfaces until all the Homatropine with which it is 
charged is absorbed. Moreover, since the pure alkaloid is less soluble in 
albumino-saline solutions—like the lachrymal fluid—than are its salts, the former 
is to be preferred since the cyclopegic action is thus distributed over a longer 
period. All those who have used Atropia with vaseline, lanoline, etc., will 
appreciate the difference in effect upon the ciliary body and nasopharynx 
between these mixtures and watery solutions of equal strength. 
That Cocaine and all its salts employed alone exert an evanescent influence 
upon the accommodation, is well known. As Nettleship8 has shown (if applied 
persistently every few minutes for an hour) a very decided degree of cyclopegia 
is brought about—which begins to disappear in fifteen minutes after the last 
application—and the muscle regains full control in another three quarters 
of an hour. In conjunction with Homatropine, however, the paralyzing effects 
of each drug are decidedly increased. So far as I can learn we are entirely 
indebted to the experiments of Tang and Barrett, just referred to, for a demon- 
stration of this truth. These observers employed a two per cent, solution, in 
castor oil, of the alkaloids Homatropine and Cocaine, and the results obtained 
are from a single application of this mixture. The following extracts from 
their tables will serve to illustrate the contention : 
Avfragf Action of Homatropinf and Homatropink + Cocainf. 
Dilatation of 
Pupil. 
RECESSION 
OF 
Near Point. 
RECESSION 
OF 
Far Point. 
Diminution 
of Range 
of Acc. 
Time of commencement 
Horn 
x3-33 
6.67 
5- 
of action, in minutes . . 
Horn. + Coc. 
10. 
6.67 
5-83 
Time of maximum action, 
Horn 
60. 
61.67 
63.33 
65- 
in minutes 
Horn. + Coc. 
30. 
61.67 
77- 
59-17 
Time of cessation of action, 
Horn 
21.67 
8-75 
8-75 
in hours 
Horn. + Coc. 
48. 
25.67 
25.67 
* Trans. Am. Oph. Socy., 1875, p. 355. 
3 It will thus be seen that Homatropine + Cocaine dilates the pupil and 
paralyzes the accommodation more rapidly than Homatropine alone, and that 
these results are more lasting and more decided than those following the employ- 
ment of the latter. 
It is a matter of speculation how Cocaine increases, as it is now known to do, 
the cyclopegic and iridoplegic effects of all the other mydriatics. Jourevitsch 
and Maklakoff* both agree that Cocaine favors the absorption of other drugs, 
the latter calling it the “ multiplicator ” of Atropine and Eserine. 
Of course the greater effect of mixtures over members of a combination 
given singly is not a new observation in therapeutics. Witness, for example, the 
greater diuretic influence of the bromine and sodic salicylate compounds over 
the same amount of either of these agents given alone; or Brown-Sequard’s 
discovery! that a given dose of the mixed bromides (KBr and NH4Br) exerts a 
greater sedative influence than the same quantity of either drug. My own 
notion is that Cocaine renders the outer epithelial layer of the cornea (and 
conjunctiva) more pervious to the Homatropine or the other drug. It certainly 
makes it more liable to abrasion, as every one knows, and if a thoroughly 
cocainized cornea be carefully examined with a Coddington lens, minute fissures 
will often be observed running in all directions through the superfical epithelium. 
It is comprehensible that a similar effect is produced upon the conjunctival 
epithelium also, so that both miotics and mydriatics are quickly absorbed into 
the lymph spaces and capillaries and soon reach the interior of the eye. 
Although I believe that the castor-oil mixture of Homatropine and Cocaine, 
introduced by Bang and Barrett, is an efficient agent in determing refractive 
errors, there are, it seems to me, some objections to it. In the first place an 
oily film forms upon the corneal surface which stands in the way of a distinct 
view of the fundus and even interferes somewhat with vision. I think, also, 
that the same film makes it more difficult, than when the oily menstruum is not 
employed, to decide just when the shadow “turns” in the examination by 
retinoscopy. These effects are partially due to the difference in the refractive 
indices of the cornea and castor oil and partly to the fact that the film is not 
always uniformily distributed over the corneal surface. 
Thinking that the exhibition of solid Homatropine and Cocaine would best 
suit their peculiar cyclopegic action, I made a number of trials with these 
drugs, in the form of discs, with various excipients. These, used alone and in 
combination, were chiefly boracic acid, dextrin, linseed jelly, gum acacia, 
Irish moss, quince-seed jelly, marshmallow jelly, gum tragacanth, and various 
kinds of gelatine. These experiments led me to select discs containing a large 
percentage of the latter, as the best medium for exhibiting Cocaine and Homa- 
tropine, and I have had the most satisfactory results from them in single doses 
of one-fiftieth grain each. These discs or lamellae were manufactured for me 
by Messrs. Wyeth & Brother, of Philadelphia, and in some respects are 
superior to the best French and English makes. They are absolutely non- 
irritant and immediately become soft and pliable when placed upon the ocular 
conjunctiva. To this they readily attach themselves and remain in situ until 
they are entirely (and slowly) dissolved by the lachrymal secretion. The cost 
* Ann. Univ. Med. Sciences, vol. iv., 1889, p. 157. 
f “ The Physiological and Therapeutical Action of the Bromides.”—Clark and Amory, p. 105. 
4 of these discs is also much less than Homatropine solutions of the same 
strength (of which nine-tenths is probably wasted) used for determining refrac- 
tive errors, because nearly all the drug is absorbed in a manner most likely to 
do effective work. In one disc there is exactly the same quantity of Homa- 
tropine that is contained in one minim of a two per cent, solution and I have 
calculated that in the lamellar form it is ten times more efficient than when 
dissolved in water. 
The best results seem to follow the observance of these rules: 
First.—Having dampened a small camel-hair brush, touch with it a disc 
previously placed on a piece of clean, dry paper, when the disc will readily 
stick to the brush. Telling the patient to look up, draw down the lower lid and 
place the opposite surface of the lamella against the exposed scleral conjunctiva, 
towards the outer canthus. It at once adheres to the former and the patient is 
now told to close the eye. 
Second.—The patient must keep his eye shut until the examination is made. 
This precaution is taken to lessen the danger of an abraded cornea and to avoid 
the disagreeable and annoying desiccation of the corneal epithelium which 
sometimes follows the introduction of Cocaine into the conjunctival sac. The 
moisture upon the lids prevents all this. 
Third.—The examination must begin not earlier than sixty and not later 
than ninety minutes after the introduction of the discs so as to take advantage 
of the period of maximum cycloplegia. 
Fourth.—In persons under twenty-five, or where there is reason to suspect 
accommodative spasm, I supplement the single disc by another, inserted fifteen 
or twenty minutes after the first. 
Fifth.—I always warn the patient that there will be a little smarting after 
the introduction of each disc. This, due chiefly to the Cocaine, passes off 
within a few minutes. 
Sixth.—Following Tang and Barrett’s experiments, I frequently introduce 
after the examination has been completed, a Wyeth Eserine disc (one one- 
thousandth grain)—made with gelatine if used shortly after the others, or a 
compressed disk if introduced the next day—or a single drop of the castor-oil 
solution (one-tenth per cent.) of Eserine. In most cases this is sufficient to 
make it possible for the patient to do effective work within twelve hours and 
in all instances within twenty-four hours. To avoid encroachment upon 
business time I frequently use the lamellae in the afternoon, and, by inserting 
a single Eserine disc after the completion of the examination, the patient is 
enabled to resume near work the next morning. In cases where this is not 
possible I direct him to return for a second application. The great advantage 
of this procedure over Atropine, Duboisine and Hyoscine in the case of 
business men and women is apparent. 
Seventh.—Both Cocaine and Homatropine are to some degree hygroscopic ; 
discs prepared with these drugs should, therefore, always be kept in an air- 
tight receptacle. 
I append short reports of a few cases, chosen from a large number, into 
whose eyes (after the refraction has been determined by means of discs 
containing one-fiftieth grain each of Cocaine and Homatropine, employed in 
the above mentioned manner) a one per cent, aqueous solution of Atropine had 
5 been instilled three times daily for three days and longer. In some instances 
the degree of Myopia or Hypermetropia developed by the Atropine was a 
shade higher than from the use of the discs; sometimes it was slightly less. 
Occasionally there was a slight variation in the axis of the cylinder accepted 
by the patient. On the whole, however, the differences were not greater than 
those which one would expect in observations made under similar conditions 
by different oculists. In a number of instances the position of the near point 
was noted by the Eandolt optometer and convex glasses at the moment of greatest 
cycloplegia from the discs; it did not vary from that established later on 
by Atropine. The refraction was measured by means of the Javal-Schiotz 
ophthalmometer and test lenses. 
Case L— M. 8., set. 13. Occasional convergent squint for four or five 
years. Asthenopia after half-hour at school-work. 
R. E. V. with + sD = fg. 
D. E. with sph. -f- 5 D 3 cyl. -f- 1 D ax. 90° = fg. 
Examined subsequently by Dr. Stevenson under Atropine with same results. 
Case lI.—C. F., set. 18. Headaches and other asthenopic symptoms. 
R. E. with -f- 4-50 3 cyl. + 1 ax. vert. = fg —. 
E. E. with 4.50 D 3 cyl. + 0.75 ax. vert. = fg. 
Dr. S. reports same results from Atropine in R. E., but in D. E. + 4 D 3 + 1 E 
ax. vert. = |g +• 
Case lII.—A. F., set. 16, seamstress. Supraorbital headaches, etc. 
D. E., + 2-5° 3 cyl- + 1 D., ax. 90° = |g. 
R. E., + 1.25 C cyl. + 1.25 ax. 90° = .ft—. 
Atropine three days. Dr. S. reports precisely same result. 
Case IV.—Miss S. Decidedly asthenopic symptoms after reading or other 
near work. Dr. S. and I found the same refractive error in both eyes; I, after 
the use of four lamellae in ninety minutes, and he, subsequent to four days’ 
instillation of Atropine ; i. e. R. and D. sph. -)- 3.50 3 cyl. + 3.50, ax. 85° = fg. 
Case V.—W. T., set. 16. Has had a blepharo-conjunctivitis nearly whole 
life ; Disc in each eye at 3 p.m.; another at 3.20. Examination at 4.15. 
R. E. with —0.50 3 cyl. —0.75 ax. 130° = +. 
D. E- with —0.25 = +• 
No change after Atropine. 
Case VI.—E. K., set. 13. No ocular symptoms. ' After Discs : 
R. and D. E. with -(- 0.50 = f +• 
Dr. Stevenson’s report, after three days’ Atropine: 
“R.E. = ft with + 0.25. D. E., same.” 
I have to thank Prof. Haines, of Rush Medical College, and Dr. Stevenson, 
late House Surgeon of the Illinois Eye and Ear Infirmary, and Messrs. Wyeth 
& Brother, of Philadelphia, for their kind assistance during these investigations. 
6 In addition to those mentioned as foot notes I am indebted for valuable informa- 
tion to the following instructive papers: 
1 Rang and BarreTT; “The Action of Myotics and Mydriatics ”—Oph. 
Hosp. Reports, vol. xi., pp. 130 and 219. 
2 Screw,: “A New Mydriatic.”—Phila. Med. Times, October 1880, pp. 
7 and 47. 
3 Pautynski : “Pilocarpin und Homatropin.”—Klin Mondtsbl. fiir Aug- 
enheilkunde, 1880, S. 343. 
4 Jackson : “Homatropine Hydrobromate.”—Phila. Med. News, 1886, 
p. 88. 
5 Holt : “The Inefficiency of Hydrobromate of Homatropine in Controll- 
ing Accommodation.”—Trans. Am. Oph. Socy., 1889 
6 Oliver : ‘ ‘ The Comparative Action of Hydrobromate of Homatropine 
and of Sulphate of Atropia upon the Iris and Ciliary Muscle. ’—Am. Jour. 
Med. Sciences, July 1881, p. 150. 
7 RiSLEY and Randall: “Value of the Hydrobromate of Homatropine 
in Ophthalmic Practice.”—Trans. Am. Oph. Socy., 1881, p. 22. 
8 NettlEShip : “ On Cocaine in Ophthalmic Practice. ”—Trans. Oph. Socy., 
United Kingdom, vol. v., p. 226. 
7