|Year : 1973 | Volume
| Issue : 4 | Page : 156-160
A study of pupil shape and size by sympathomimetics
IS Jain1, KC Nagpal1, PL Sharma2
1 Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
I S Jain
Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Chandigarh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Jain I S, Nagpal K C, Sharma P L. A study of pupil shape and size by sympathomimetics. Indian J Ophthalmol 1973;21:156-60
|How to cite this URL:|
Jain I S, Nagpal K C, Sharma P L. A study of pupil shape and size by sympathomimetics. Indian J Ophthalmol [serial online] 1973 [cited 2019 Jun 18];21:156-60. Available from: http://www.ijo.in/text.asp?1973/21/4/156/34621
| Introduction|| |
There are two opposing forces, the tonic pull of radial muscle fibres having a sympathetic innervation tending to dilate the pupil and the circular muscle fibres having parasympathetic innervation tending to constrict the pupil. The mechanism of dilatation of the pupil produced by sympathomimetics is controversial. Whether it is achieved by relaxation of the circular constrictor fibres or it is an active contraction of radial dilator muscle fibres. The theory of active relaxation of sphinctef was supported by JOSEPH,  YONKMAN  and BEAN AND BOHR  by observing that adrenergic agents are much more potent in relaxing sphincter pupillae than contracting the dilator pupillae. LOWENFELD  showed that sympathomimetics such as, epinephrine, phenylephrine and ephedrine dilate the pupil by active contraction of dilator pupillae.
There have been numerous attempts to explain the mechanism of action of sympathomimetics, whether it is through alpha or beta receptors. AHLQUIST  concluded that human iris tissue contains only alpha receptors and sympathomimetic drugs act through these receptors only. This view has been subsequently supported by BENNETT, REINKE, ALPERT, BAUM AND LEON.  So far there is no study to show whether beta receptors exist in the human iris and what is their distribution, and what is the shape of the pupil when it dilates under the effect of sympathomimetics? This study was undertaken to investigate these problems.
| Material and Methods|| |
Thirty nine cases (78 eyes) were selected from eye out patient department. Only those cases who had come for routine check up (refraction and fundus examination) were taken. Cases with diseases of anterior segment of the eye were deliberately left out. The following drugs were used topically, after preparing fresh solutions, in the eye out patient department.
The dosages refer to the weights of the salts. Two alpha receptors stimulants, phenylephrine hydrochloride and metaraminol hydrochloride (Araminol), three alpha and beta receptor stimulants, epinephrine hydrochloride, tyramine hydrochloride and ephedrine sulphate, one beta receptor stimulant only isoprenaline sulphate and one parasympatholytichomatropine sulphate were tried. The strengths of the solutions varied between 1-5%. Two instillations were made at an interval of 5 minutes. The pupillary diameters were recorded before first instillation and then at intervals of fifteen minutes each for 60 minutes.
| Observations|| |
The age group of the 39 cases studied varied from 15 years to 56 years. Most of the patients were emmetropes, however, five patients were ametropes, three were high myopes, and one high hypermetrope and one had unilateral high myopia. The following observations were made:
5 % Phenylephrine hydrochloride (Drosyn) on the pupil
It was observed that Graph I, [Figure - 1] dilatation of the pupil started within 15 minutes and it was vertically oval at 30 minutes, when the vertical and horizontal diameters were 5.5 mm and 4.5 mm respectively. The pupils became circular in about 60 minutes.
1 % homatropine sulphate on the pupil
This can be observed in graph I again. The pupil dilated circularly with this drug. The dilatation started approximately after fifteen minutes, but ultimate dilatation was slightly less than that observed with phenylephrine.
1 and 5% Adrenaline Hydrochloride and 1 and 517c Isoprenaline sulphate (neopinine) Graph II)
1 % strength of adrenaline and isoprenaline had no effect on the pupil, however, - with 5 % strength of adrenaline hydrochloride, the pupil dilated vertically oval, but 5 % neoepinine did not alter the pupillary size.
3% and 5% Ephedrine sulphate and 11% and 5%. Metaraminol on the pupil (Graph I and II).
It was observed that 3 % ephedrine solution had mild mydriatic action while 5 % produced marked dilatation (Graph II) of the pupil. Metaraminol in 1 % strength had no effect on the pupil, but in 5 % strength dilated the pupil vertically oval.
Effect of 2 % Tyramine on the pupil: (Graph II)
This again dilated the pupil vertically oval but response with this drug was quick in onset and subsided also quickly.
Another important observation was that in cases having dark coloured iris, these drugs did not affect the pupil even in higher strengths.
| Discussion|| |
Sympathornimetics are known mydriatics since the turn of the century. Adrenaline was the first drug in this group which was found to have mydriatic action.
CHEN AND POTH  described mydriatic action of ephedrine, while HEATH  studied the effect of phenylephrine (Drosyn) on the pupil and found that it also dilated the pupil. ABBOT AND HENRY  described the mydriatic action of paredrine and BARBAE AND SMITH  reported that it is as good a mydriatic as phenylephrine. AHLQUIST  was the first to put forward the view that human iris contains only alpha receptors and there are no beta receptors. This view has been supported by many authors including LOWENFELD  and BENNETT et al . 
The results obtained in the present study show that drugs which stimulate either alpha receptors or alpha and beta receptors have dilating effect on the pupil. Thus phenylephrine and metaraminol which act on alpha receptors only, and adrenaline, tyramine and ephedrine which stimulate both alpha and beta receptors dilate the pupil, whereas isoprenaline which stimulates beta receptors only had no effect on the pupil. BENNETT et al  in a comparative study of the role of sympathomimetics on the pupil reported that isoprenaline also dilates the pupil on intraocular injection, but the concentration of the drug required was very high. This may be due to the fact that isoprenaline has also got some alpha receptor stimulating activity. These results are in agreement with the view of AHLQUIST,  LOWENFELD  and BENNETT et al  that human iris contains alpha receptors only.
The other observation noted was that the strength of the drugs required to dilate the pupils has got to be quite high. Thus metaraminol 1 % and adrenaline 1 % had no effect on the pupil and 3 % ephedrine had a very slight mydriatic action. A 5 % solution of these drugs produced a good mydriatic action. The systemic side effects reported in the form of extrasystoles, tachycardia etc., were not noted in our series. However, one patient complained of slight smarting sensation in the eye with metaraminol and patients in whom isoprenaline was instilled had marked conjunctival congestion. Thus, all the drugs were fairly safe on topical instillation. In most of the cases, pupils started dilating within 15 minutes and full mydriasis was achieved within 45 minutes.
Another important observation made in this study was about the shape of the pupil. We found that with sympathomimetics shape of the dilated pupil became vertically oval, whether it was with alpha receptor stimulants or with drugs which stimulated both alpha and beta receptors. This is in sharp contrast to the circular shape of the pupil dilated with homatropine. Mostly the shape of the pupils was vertically oval [Figure - 1],[Figure - 2], but with metaraminol it was predominantly kidney shaped. [Figure - 2]. There appears to be a stronger pull on the pupil at12 O'clock and 6 O'clock meridians. On the temporal side pupil dilates last of all. Why the pupil assumes this shape is not clear to us. It may be that the radial fibres may be more crowded at 12 and 6 O'clock meridians and where pupil becomes kidney shaped upper nasal and lower nasal sectors may have more of these receptors. We have no histological proof in this respect. However, future careful histological and electronmicroscopic search in this regard may prove it, one way or the other. SPIERS AND CLANE  had observed vertically oval pupil with 10% dopamine.
There is a strong resemblance in the pupillary shape in cases with acute congestive glaucoma and cases dilated with sympathomimetics. Acute congestive glaucoma is a disease of nervous and anxious type of personalities who are prone to autonomous nervous system imbalances. The acute pain present in acute congestive glaucoma may trigger autonomic nervous system imbalance and sympathetic overactivity in these cases and may dilate the pupil vertically oval. This is still a matter of conjecture and we have as yet nothing more to prove it. However, it brings out interesting possibilities and it may provoke further investigations in this direction.
Our study lent further support to another earlier observation by CHEN,  who found that Chinese and Negroes are less susceptible than Europeans to mydriasis by ephedrine, cocaine and euphthalmine. In our study we observed that in people with dark coloured iridis, the response to sympathomimetics was poor in general when these were used as mydriatics. In people with light coloured iris, the pupils dilated relatively quickly and with low concentration of the drugs.
| Summary|| |
Role of sympathomimetics as mydriatics has been studied and a few important observations have been made. Sympathomimetics dilate the pupil vertically oval just like in an attack of acute congestive glaucoma. Higher strengths of the drugs are required to produce mydriasis. The side effects with topical instillations of sympathomimetics are very few and thus these are fairly safe mydriatics. Further weight has been lent to earlier hypothesis that human iris contains only alpha receptors and that the dilatation of the pupil produced by sympathomimetic drugs is due to an active contraction of dilator pupillae.
| References|| |
Abbot, W. D. and Henry, C. M.: Paredrine. Clinical investigation of sympathomimetic drugs. Amer. J. Med. Sc. 193: 661, 1937.
Ahlquist, R. P.: A study of adrenotrophic receptors. Amer. J. Physiol. 153: 586-600, 1948.
Barbae, R. P. and Smith, W. O.: A comparative study of Mydriatic and Cycloplegic agents, in human subjects without eye diseases. Amer. J. Ophthal. 44: 617, 1957.
Bean, J. W. and Bohr, D. F.: Effects of Adrenaline and Acetylcholine on isolated iris muscle in relation to pupillary regulation. Amer. J. Physiol. 133: 106, 1941.
Bennett, D. R., Reinke, D. A., Alpert, E., Baum, T. and Leon, H. W.: The action of intraocularly administered Adrenergic drugs on the iris. J. of Pharm. and Therap. 134: 190, 1961.
Chen, K. K. and Poth, E. I.: Racial differences as illustrated by mydriatic action of Cocaine, Euphthalmine and Ephedrine. J. Pharm. and Exp. Therap. 36: 429, 1929.
Heath, P.: Neosynerphrine Hydro ,
chloride. Some uses and effects in Ophthalmology. Arch. of Ophthal. (Chicago) 16: 837, 1936.
Joseph, D. R.: Amer. J. Physiol. 42: 608, 1917. Quoted by Bennett, et al. in ref. 5.
Lowenfeld, I. E.: Docum, Ophthal. 12: 185, 1958. Quoted by Bennett, et al. in ref. 5.
Spiers, A. S. D. and Calne, D. B.: Action of Dopamine on the human iris. Brit. Med. Journal, 4: 333, 1969.
Yonkman, F. F.: Journal of Pharm. and Therap. 52: 290 Rev. 1934. Quoted by Bennett et al. in ref. 5.
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4]