STUDIES ON THE USE OF ANTIHISTAMINES IN CATARACT SURGERY*

THOMAS MITCHELL FILE, M.D. Davton, Ohio

INTRODUCTION

Ophthalmic surgeons during cataract ex­tractions occasionally encounter a miotic pupil despite adequate preoperative mydri-asis. Since retention of a round pupil follow­ing cataract extraction is greatly desired, it would be advantageous to have an agent that would obviate the necessity to sacrifice a round pupil to facilitate the delivery of the lens. Any one of the antihistaminic drugs may be such an agent.

As stated by Adler1 histamine is a potent miotic drug, causing constriction of the pupil by a direct action on the smooth muscle of the iris sphincter. This miosis is pro­duced by histamine even after the iris sphinc­ter muscle has been paralyzed by such a my-driatic drug as atropine. It has long been known that histamine, or a histaminelike substance, called H-substance by Lewis,2 is liberated by injured tissue cells. It would seem that the incision for cataract extrac­tion and the iridectomy constitute sufficient injury to the tissues to cause the release of this histaminelike substance.

Several antihistaminic drugs have been shown by D'Ermo3 on isolated iris muscles to relax the spasm of the iris sphincter in­duced by histamine. The studies of Genaz-zoni and Alajmo* showed that, in man, Neoantergan (an antihistamine) produces a mild mydriasis and neutralizes the miotic action of histamine.

Epinephrine, a sympathomimetic drug which stimulates the iris dilator muscle, is frequently instilled directly into the anterior chamber in cataract surgery to produce or maintain mydriasis. However, miosis may occur and persist in occasional cases in spite

* From the Department of Ophthalmology, the Ohio State University, Columbus, Ohio. This study was presented in partial fulfillment of the require­ments for the degree of Master of Medical Sci­ence.

of good preoperative mydriasis and the use of epinephrine during the operation.

This study attempts to determine if an an­tihistamine, administered preoperatively, will produce a significantly lower incidence of miotic pupils during cataract surgery.

EXPERIMENTATION

In order to determine the effectiveness of antihistamines in preventing miosis during cataract surgery a series of animal experi­ments and studies of human patients under­going cataract surgery were done. Albino rabbits which appeared healthy and free of any ocular inflammation were selected. All animals were given sufficient pentobarbital sodium (Nembutal) intravenously to pro­duce unconsciousness a few minutes prior to the surgical procedure. The approximate dosage used was 1.0 ml. (60 mg./ml.) for each five pounds of body weight; 0.5-per­cent 2-diethylaminoethyl-3-amino-4-propoxy-benzoate hydrochloride (Ophthaine) was used for topical anesthesia. Epinephrine (adrenalin chloride) 1:1,000 solution was used topically for hemostasis. A retrobulbar block and facial nerve block for eyelid akinesia were done using 2.0-percent lido-caine hydrochloride (Xylocaine) with epi­nephrine 1:100,000. Prior to the operative procedure the pupils were dilated with atro­pine sulfate (1.0-percent solution) and phe-nylephrine hydrochloride (Neosynephrine, 10-percent solution) each instilled topically twice with an interval of one hour between the instillations. The pupils were measured and the size in mm. recorded just prior to be­ginning the surgical procedure. In all cases both the right and left eyes received the same drugs and underwent the same surgical pro­cedure, with the one exception that the anti­histamine was administered after the com­pletion of the procedure done on the right eye and prior to that done on the left eye. In

1240

ANTIHISTAMINES IN CATARACT SURGERY 1241

this manner the right eye served as a con­trol study in all animals.

After the preceding preliminary pro­cedures were performed on each rabbit the following experimental studies were done.

1. In four rabbits histamine acid phos­phate 0.275 mg. (0.1 ml. of solution) was injected directly into the anterior chamber of both eyes. The pupils were measured just before the injection and again two minutes after the injection.

In the case of the first rabbit the antihis-tamine (Dramamine, 5.0 mg.) was injected directly into the anterior chamber of the left eye two minutes prior to the injection of histamine into this eye.

With the second rabbit the antihistamine (Phenergan, 25 mg./ml.) was administered topically, two drops every 10 minutes for three instillations, to the left eye prior to the histamine injection.

With the third and fourth rabbits the anti­histamine (Dramamine, 12.5 mg.) was ad­ministered intravenously after the injection of histamine into the right eye and 30 min­utes prior to the injection of histamine into the left eye.

2. On seven rabbits surgical procedures were carried out in a manner similar to cat­aract extractions in humans. Penetrating corneal incisions were made just central to the limbus and around half the circumfer­ence of the cornea after three sutures were preplaced. A peripheral iridectomy was then performed in each case. For each eye the diameter of the pupil was measured and re­corded just prior to the surgical procedure and again just after the performance of the iridectomy. The surgery was done in a simi­lar manner in both eyes of all the animals in this group.

With five rabbits the antihistamine (Phen­ergan, 12.5 mg.) was administered intra­venously after the completion of surgery on the right eye and 30 minutes before the be­ginning of the surgical procedure on the left eye.

With two rabbits the antihistamine (Phenergan, 25 mg./ml.) was administered

topically to the left eyes, two drops every 10 minutes for three instillations, prior to the surgery on the left eyes.

For the human study a series of eyes of patients undergoing cataract extractions was observed. The surgery was performed at the University Hospital by staff physi­cians and resident physicians, including my­self. The selection of patients for the study was random with the exception that cases in which there was poor preoperative my-driasis and cases in which a complete iridec­tomy was planned were not included in this study.

The preoperative medications used were secobarbital sodium (Seconal) and meperi-dine hydrochloride (Demerol). The topical anesthetic and mydriatic agents and the local anesthesia given were similar to those used in the animal experiments. The surgery was similar to that performed on the rabbits ex­cept that, in most cases, a conjunctival flap was used. The size of the pupil was ob­served before surgery and again after the iridectomy was performed. This was re­corded as either well dilated or poorly di­lated. After the anterior chamber was opened adrenalin chloride (1:1,000 solu­tion) was dropped directly onto the iris to help maintain mydriasis.

Seven patients received antihistamine (Phenergan, 25 mg.) by mouth two hours prior to surgery and seven patients received a topical antihistamine administered to the eye before surgery. The topical preparation used was Allergan's ophthalmic antihis­tamine decongestant solution containing 0.1-percent pyrilamine maleate. This was given every 10 minutes for three instillations be­fore surgery. As a control group, 13 eyes which received no antihistamine were ob­served during cataract extraction.

RESULTS

Tables 1 and 2 summarize the results of the animal experiments, Table 3 those of the human study. It is shown in Table 1 that histamine, injected directly into the anterior chamber, caused constriction of the pupil of

1242 THOMAS MITCHELL FILE

TABLE 1 EFFECT OF HISTAMINE INJECTED INTO THE ANTERIOR

CHAMBER OF BOTH EYES. I N ALL ANIMALS THE RIGHT EYE RECEIVED NO ANTIHISTAMINE

WHILE THE LEFT EYE DID

Route of Antihistamine Administration

Rab- P u p i l S i z e . - t before Injec-No.

Pupil Size after Injec­

tion of Hist- tion of Hist­amine (mm.) amine (mm.)

Injected into an­terior chamber

Topical

Intravenous

O.D. 10.5 O.S. 11.0

O.D. 12.0 O.S. 12.0

O.D. 12.0 O.S. 12.0

O.D. 7.0 O.S. 11.0

O.D. 10.0 O.S. 12.0

O.D. 9.0 O.S. 12.0

O.D. O.S.

11.S 12.0

O.D. O.S.

9.5 12.0

all eyes receiving no antihistamine, while no constriction of the pupil occurred in the eyes that had previously received an antihista­mine.

Table 2 shows that, in the animal eyes undergoing cataract surgery, the pupillary constriction was at least twice as great in the eyes receiving no antihistamine as in those in which an antihistamine was ad-

TABLE 2 EFFECT OF SURGERY (CORNEAL INCISION AND IRI-

DECTOMY) ON BOTH EYES. IN ALL ANIMALS THE RIGHT EYE RECEIVED NO ANTIHISTAMINE

WHILE THE LEFT EYE DID

Route of Rab- Pupil Size be- Pupil Size af-Antihistamine bit fore Surgery ter Surgery Administration No. (mm.) (mm.)

Intravenous

Topical

5

6

7

8

9

10

11

O.D. O.S.

O.D. O.S.

O.D. O.S.

O.D. O.S.

O.D. O.S.

O.D. O.S.

O.D. O.S.

12.0 12.0

13.0 12.5

13.0 13.0

11.5 12.0

12.5 13.0

12.0 12.0

12.0 12.0

O.D. 10.5 O.S. 11.5

O.D. 11.5 O.S. 12.0

O.D. 11.5 O.S. 12.5

O.D. 10.0 O.S. 11.5

O.D. 10.5 O.S. 12.0

O.D. 11.0 O.S. 11.5

O.D. 10.0 O.S. 11.5

TABLE 3 EFFECT OF ANTIHISTAMINE ON PUPIL SIZE

DURING CATARACT SURGERY

Number Re-of Eyes mained Con- % Con-

in Well stricted stricted Group Dilated

No antihist­amine

Antihistamine by mouth

Topical antihistamine

13

7

38.5

14

14

ministered prior to the surgery. It is shown in Table 3 that pupillary con­

striction occurred almost three times as often in human eyes undergoing cataract surgery that received no previous administration of an antihistamine as in those eyes in which an antihistamine was given preoperatively, either topically or by mouth.

S U M M A R Y AND CONCLUSIONS

A study was done on both rabbit and hu­man eyes undergoing cataract surgery in an attempt to determine if antihistaminic drugs administered preoperatively would reduce the incidence of pupillary constrictions dur­ing cataract surgery. A preliminary study on four rabbits showed that an antihistamine given intravenously, topically, or by injec­tion into the anterior chamber prevented the constriction of the pupil, caused by his­tamine injected into the anterior chamber, which occurred in eyes in which no anti­histamine was given.

It was observed that in the eyes of seven rabbits undergoing cataract surgery the pu­pillary constriction was at least twice as great when no antihistamine was given pre­operatively as when an antihistamine was ad­ministered either topically or intraveneously.

A study of 27 human eyes during cataract extraction showed that the preoperative ad­ministration of an antihistamine reduced the incidence of miosis during the surgery al­most threefold.

ANTIHISTAMINES IN CATARACT SURGERY 1243

Although the number of eyes observed in this study is small, it is concluded that the preoperative administration of an antihis-tamine, either topically or systemically, will

substantially reduce the incidence of miosis during cataract surgery.

32 North Main Street (1).

REFERENCES

1. Adler, F. H.: Physiology of the Eye. St. Louis, Mosby, 1953. 2. Best, C. H., and Taylor, N. B.: Physiological Basis of Medical Practice. Baltimore, Williams &

Wilkins, 1950. 3. D'Entio, F.: Antistaminici e occhio, Nota VII, Azione degli antistaminici sintetci sui muscoli isolati

del iride. Boll. Ocul., 33:8,1954. 4. Genazzani, E., and Alajmo, A.: L'azione del istamina e del neoantergan sulla pupilla. G. ital. Oftal.,

4:6, 1951.

A NEW SUTURE FOR CATARACT SURGERY* M A R T I N BODIAN, M.D.

Brooklyn, New York

INTRODUCTION

Removal of corneoscleral sutures follow­ing cataract extraction may cause more ap­prehension in the patient, frustration to the surgeon and danger to the eye than the origi­nal surgery.

In early 1955 I conceived a method of suture placement which makes suture re­moval far safer and facile, while preserving the advantages of secure black silk closure. Since that time, and having used the tech­nique on 103 cases, I am convinced that suture removal can be a routine procedure free from danger and difficulty. A further advantage of this suture is that it produces a highly effective wound closure, as will be demonstrated.

Kirby1 described the removal of sutures in great detail, indicating the need for gen­eral sedation as well as local anesthesia in many cases. To him, as to all ocular sur­geons, suture removal was a matter of con­siderable concern. Atkinson2 describes the difficulties with catgut sutures but concludes, "However, the advantage of not having to

remove the sutures more than outweighs the disadvantages."

TECHNIQUE

Preoperative preparation includes proper sedation, cleansing of the eye, local anes-

• thesia (including retrobulbar injection), akinesia, and softening of the globe by mas­sage. The lid speculum and superior rectus bridle suture provide proper exposure.

After superior hemiperitomy, a fornix-based flap is undermined, leaving the limbal area free and uncluttered. A semipenetrating vertical limbal groove from the 3- to 9-o'clock positions is made with a Bard Parker, No. 15, blade. The eye is now ready for sutures.

TECHNIQUE OF SUTURE PLACEMENT (figs. l t o 4 ) The scleral lip of the limbal groove is

grasped with sharp scleral fixation forceps at the l:30-o'clock position. The cornea is entered with the No. 780 Ethicon needlet

* From the Brooklyn Eye and Ear Hospital. Pre­sented before the New York Academy of Medicine, Section on Ophthalmology, February 15, 1960.

t This is an extremely sharp atraumatic (swagged) needle. Other sharp needles that require threading are not so satisfactory since they require a double thickness of silk to be pulled through the three-mm. corneal stromal tract.