Primary Angle-Closure Glaucoma*

PRIMARY ANGLE-CLOSURE GLAUCOMA* INVESTIGATIONS USING RONALD F.

10% PHENYLEPHRINE EYEDROPS L O \ /E,

F.R.A.C.S.

Melbourne, Australia

Provided gonioscopic appearances are favorable, the safest surgery for the prophylaxis or treatment of primary angle-closure glaucoma is peripheral iridectomy. However, even after uncomplicated surgery and in the absence of peripheral anterior synechiae, one third of the number of the angles will remain narrow. A previous paper1 showed that, if the pupils of these narrow-angle eyes are dilated by mydriatics such as homatropine or cyclopentolate, one half to two thirds of these angles will close by folding of the iris against the trabeculae, despite the presence of open peripheral iridectomies. Tensions may rise to the 50's and tonography will then show greatly reduced outflow but, if the pupils are dilated to the same extent by using 1-epinephrine base eyedrops (Eppy 1%), the angles will not close and the outflow will probably improve.2 During the early days after peripheral iridectomy, forced pupil mobility is desirable to prevent the formation of posterior synechiae. Because strong epinephrine eyedrops will then give pupil dilatation without angle-closure their use appears to be indicated; but, although epinephrine dilates some pupils widely, its mydriatic effect is frequently inadequate. It is known that 10% phenylephrine eyedrops dilate pupils better and their evanescent action gives good pupil mobility, but no information is available cnocerning their risk of postoperative angle closure. INVESTIGATIONS

From a large series of patients who had received surgery for various types of primary angle-closure glaucoma, 31 patients were selected. Those whose eyes showed * From the Glaucoma Unit, Royal Victorian Eye and Ear Hospital, and the Ophthalmic Research Institute of Australia.

gross structural abnormality from glaucoma or surgery (persistent angle closure greater than one third, drainage blebs or severe iris damage) have been excluded. Sixty eyes were appropriate for the tests to be described. Some of the eyes had been involved in attacks of subacute or acute angle-closure glaucoma and the remainder were fellow eyes of others that had suffered such attacks. All were in a quiet condition at least two months after peripheral iridectomy and no treatment was being used. Gonioscopy was performed at a HaagStreit 900 slitlamp, using a Goldmann goniolens. Applanation tonometry was performed followed by four-minute tonography (with a Mueller tonographer), after which two or three lots of 10% Neosynephrine eyedrops were instilled at 10-minute intervals. Tonography was repeated between two and two and one-half hours later, and gonioscopy followed while the pupils were dilated. RESULTS

The results, tabulated in the same manner as the previous tests conducted with homatropine 4% and with Eppy 1%, are summarized in Table 1. If homatropine tonography is tabled above Eppy tonography, a marked shift to the right is shown because the tropine mydriatics frequently raised tensions and reduced outflow, whereas, Eppy 1% caused little change in tension and predominantly increased outflow. The 10% phenylephrine results qualitatively resemble those of Eppy and are different from the homatropine group. There were no unfavorable rises of tension produced by 10% phenylephrine and outflow was frequently increased. Becker, Gage, Kolker and Gay3 from examinations upon 30 normal eyes concluded that, after administration of phenylephrine hydrochloride ( 10,%), the outflow

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facility and intraocular pressures were not altered although pupils dilated significantly. Their tests were repeated in one hour, whereas, the present tests permitted the drops to act for two to two and one half hours. Gonioscopy showed that following 10% phenylephrine eyedrops no angles became more narrow and consequently none closed even though the pupils usually dilated considerably more than following 4% homatropine. No peripheral iridectomies were occluded by the pupil dilatation. Gonioscopic appearances after 10% phenylephrine resembled those after Eppy 1% and could be considered safe, in contrast to many angle-closures following 4% homatropine or 1% cyclopentolate. Possible reasons for this difference in iris configuration are given in a previous paper.2 PREOPERATIVE INVESTIGATIONS

As the epinephrine and tropine groups of drugs had produced different effects relating to angle closure in eyes that had received peripheral iridectomies and had relaxed irises, it was decided to investigate if similar differences occurred when irises were ballooned in eyes with shallow anterior chambers before surgery. Patients with possible histories of subacute angle-closure glaucoma, or unoperated fellow eyes of patients who had suffered an acute attack of angle-closure glaucoma, or eyes with shallow anterior chambers and open narrow angles under treatment for

chronic simple glaucoma were selected for study. Three patients with chronic simple glaucoma and narrow angles were examined uneventfully with 10% phenylephrine; pupils dilated widely, tensions remained the same or fell a little, and outflows improved somewhat, but one angle appeared practically closed after the drops. The fourth patient gave us a fright. CASE REPORTS CASE

342

Mr. N. B., aged 73 years, had mild chronic simple glaucoma with eyes that had shallow anterior chambers measuring 1.60 mm deep with the Jaeger apparatus on a Zeiss slitlamp. His irises were ballooned and his anterior chamber angles were narrow but he had experienced no symptoms suggestive of angle-closure attacks. Two dark-room tonography tests were negative but a homatropine tonography gave a positive result for his left eye (right tension and outflow remained unchanged, left tension rose from 20 to 30 mm H g and C value fell from 0.13 to 0.05). Gonioscopically his right angle appeared approximately 60% occluded, whereas, his left angle had virtually closed. Eserine drops were administered and his pupils constricted with a return to normal tension. On another day, from 9:30 A.M. to 11:30 A.M., 10% Neosynephrine tonography was performed. His pupils were only dilated to half their possible extent but his right tension rose from 17 to 29 mm H g and his left from 22 to 39 mm H g while his right C value fell from 0.15 to 0.06 and his left from 0.11 to 0.08. His right angle appeared two thirds closed, and his left angle was smothered by iris folded against the wall in the upper half while the angle appeared closed in depth in its lower half. Oily 0.5% eserine drops were administered every 10 minutes for an hour but his tensions remained at right, 25 mm H g ; left, 40 mm Hg. Five hundred mg of acetazolamide were given orally and the es-

TABLE 1 SUMMARY OF POSTOPERATIVE REPEAT TONOGRAPHY TESTS

Tonography Test

Facility Change

Po Change

Fall Fall No Rise Rise > 2 S % < 2 5 % Change <25%, > 2 5 %

Total Eyes

Rise > 8 mm

Rise < 8 mm

No Change

13

34

22

1

34

16

15

4

1

70

Eppy 1%

0

7

23

9

1

1

5

9

23

39

Neosynephrine 10%

0

21

27

12

3

6

15

11

25

60

Homatropine or Cyclopentolate

Fall

PRIMARY ANGLE-CLOSURE GLAUCOMA erine continued. In a further two hours his tensions were right, 27 mm H g ; left, 50 mm Hg, so an injection of 500 mg of acetazolamide was given intravenously. In a further hour his tensions had fallen to 19 and 26 mm Hg, and his pupils were constricting. Next morning his tensions were right, 8.5 mm H g left, 10 mm H g and his pupils were miotic. Several days later another patient even m o r e dramatic results. CASE

gave

433

Mr. C. H., aged 80 years, attended the hospital for review of his left eye which he stated had had a hemorrhage in it one year previously. Two-percent homatropine and cocaine drops were used to dilate his pupils. His left eye showed an old thrombosis of the inferior retinal veins and a partial retinoschisis. With pupils dilated his ocular tensions were right, 22 mm H g ; left 17 mm Hg. Subsequently, he had a refraction performed under 2 % homatropine and cocaine drops. At a review examination, after homatropine and cocaine drops, his right tension rose to 50 mm H g while his left remained at 18 mm Hg. Gonioscopy showed his right angle closed by folded iris and his left angle to be narrow but open. Eserine (0.25% drops) constricted his pupils and returned his tensions to normal. He was ordered 2 % pilocarpine eyedrops three times daily. Two months later a further review with homatropine and cocaine drops gave tensions of 46 and 17 mm H g that returned to normal when the pupils were constricted with eserine. At the Glaucoma Unit his anterior chamber depths measured right 1.5 mm, left 1.8 mm with the Jaeger apparatus. After stopping the pilocarpine drops for three days, a 10% Neosynephrine tonography was performed. His left tension remained at 15 mm H g and his left outflow was unchanged, but his right tension rose from 15 to 59 mm H g and his right C value fell from 0.14 to 0.02 during the hour from 11:00 A.M. to 12:00 noon. Pupils were widely dilated and even. Gonioscopy of his right eye showed the iris thickly folded against the angle wall all around. Although his left pupil was equally dilated, the angle remained narrowly open beyond the iris folding. Five hundred mg of acetazolamide were given orally and 0.25% and 0.5% eserine eyedrops were administered every five to 10 minutes. After one and one-half hours his right tension was 69 mm H g and the pupil dilatation had not diminished. He was admitted to hospital and given 250 mg acetazolamide intravenously, and 50 mg of chlorpromazine intramuscularly. In a further three hours his right eye was unchanged except slight corneal edema had developed. H e was given a further 500 mg acetazolamide orally and shortly afterward, oral glycerine 1.0 ml/kg of body weight. After a further hour, his right tension was still 51 mm H g while his left was 8 mm H g . It was then 9:30 P.M. At 8:30 A.M. next morning his right tension was still 47 mm Hg, although this pupil was half con-

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stricted. Operation was arranged and he was given 500 ml of hypertonic mannitol solution intravenously one hour before surgery. By the time he was under the general anesthetic his right eye was very soft and difficult to incise. A full iridectomy was performed to help pull the iris out of the angle. Convalescence was uneventful and a prophylactic peripheral iridectomy was performed upon his left eye. His eyes showed no other damage. Reviewed a month later his tensions were 10 and 11 mm H g and remained unchanged after repeating the 10% phenylephrine tonography test. His C values improved from right 0.15, left 0.15, to right 0.24, left 0.23, with the phenylephrine and his angles remained well upon (Grade 3, Shaffer). The man is pleased with the result because the large pupil suits his aged lens and he no longer has to use miotic drops. A n o t h e r p a t i e n t w a s less f o r t u n a t e . CASE

475

Mrs. E. J., aged 72 years, attended to have her glasses changed. For two to three years she had noticed rainbow-colored rings around lights and her vision was dim for reading. For two weeks she had intermittent aches behind her right eye, especially after reading at night. Examination showed shallow anterior chambers and normal intraocular pressures. Homatropine and cocaine drops were used during refraction after which her tensions were still normal. She had considerable lens sclerosis and 2.5 diopters of myopia so it was uncertain whether the halos were lenticular or glaucomatous. Gonioscopy showed each iris to be ballooned and angles to be narrow but open. Goldmann visual fields were normal. At the Glaucoma Unit a dark-room test was negative. She returned another afternoon and in the presence of normal tensions at 2:15 P.M. 10% Neosynephrine eyedrops were instilled. After one hour, her pupils were dilated and her tensions were still normal so eserine drops were instilled. The patient was anxious to return home to cook the evening meal so after a short wait and more eserine she was permitted to leave. Next evening her general practitioner sent her hack to the hospital. She said that on the wayhome in the tramcar both eyes became sore and later that night she vomited. She went to bed and by next morning her right eye had cleared but her left vision was blurred and her left eye continued to be painful. Later in the day she consulted her general practitioner. Examination showed a normal right eye with a miotic pupil. Her left eye showed the redness, corneal edema, dilated pupil and glaukomflecken of acute glaucoma. She was admitted to hospital, given intensive miotic therapy and 500 mg Diamox intravenously, plus oral Diamox (500 mg) six hourly. H e r left intraocular pressure took 24 hours to subside but the angle remained closed. A prophylactic peripheral iridectomy was performed upon her right eye, and a week later when her left eye

RONALD F. LOWE

418

had quieted, an anterior sclerectomy with peripheral iridectomy was performed upon it. Convalescence was uneventful. One month later, her right vision with her previous -2.5D lens was unchanged at 6/12, but her left refraction had changed from -2.SD to -3.75D with an added cylinder of -3.5D. Fortunately, corrected left visual acuity had fallen only from 6/12 to 6/18. Gonioscopy showed her left angle to be 75% open and she had normal tensions in both eyes. These three patients illustrate that, in eyes with shallow anterior chambers, narrow angles and intact irises, angle-closure glaucoma is more likely to be precipitated by pupil dilatation using 1 0 % phenylephrine drops than by the use of 2 % homatropine and cocaine drops. CONCLUSIONS

T h e postoperative pupil dilatation tonography tests showed that 10% phenylephrine eyedrops are safe to use for pupil dilatation following peripheral iridectomy and they are generally more suitable than 1-epinephrine base eyedrops ( E p p y 1%) because they dilate pupils more quickly and more widely. Further, they should be used postoperatively in preference to homatropine or cyclopentolate which are likely to cause some angle closure and possible formation of peripheral anterior synechiae. However, no surgery is certain. Prophylactic peripheral iridectomy has been performed on 271 eyes of 450 patients on our lists, but one eye developed postoperative acute glaucoma and pupil dilatation was possibly part of the cause. CASE 35

Mrs. B. B., aged 55 years, had an uneventful prophylactic peripheral iridectomy on her right eye seven days after an iridencleisis upon her left eye which had acute angle-closure glaucoma. Following the peripheral iridectomy, her anterior chamber reformed quickly and the pupil was dilated daily with 10% phenylephrine eyedrops. On the fourth clay, severe destructive acute glaucoma developed in her right eye. On examination, marked corneal edema, heavy aqueous flare and profuse glaukomflecken were found. After the peripheral iridectomy, a flap of the posterior pigment layer remained with only a small hole in it. This small hole was possibly occluded by uveitis and the folding of the iris when the pupil

was dilated with the phenylephrine. A relative pupil block followed and a severe acute angle-closure glaucoma then developed. Unfortunately the eye reacted badly to further surgery and ultimately vision was lost. I n this patient there was an unfortunate coincidence of small iridectomy, uveitis and phenylephrine pupil dilatation, so that an acute angle-closure glaucoma occurred, similar to the cases with intact irises already described. I n contrast to the practical safety of 1 0 % phenylephrine drops in narrow-angle eyes with an iridectomy, the drops are highly dangerous in such eyes with an intact iris. W h e n shallow anterior chambers are found and pupil dilatation is required for further examination, many ophthalmologists think that the quick and evanescent action of phenylephrine drops make them safer to use than homatropine and cocaine—but this is not so because the phenylephrine pupil dilatation can cause an acute glaucoma that renders miosis extremely difficult to achieve. Becker and his colleagues 3 showed that 10% phenylephrine can overcome the constricting activity of even the strong miotics. T h e hazards are greatly increased if pupil dilatation is performed late in the afternoon, especially toward the end of consultation hours, when sufficient waiting is not given for the checking of adequate miosis. P r o vocative pupil dilatation in eyes with shallow anterior chambers and narrow angles is always potentially dangerous and these tests should only be performed during the mornings or when some hours of consultation time remain. U r g e n t admission to hospital should be available. SUMMARY

In eyes having shallow anterior chambers, narrow anterior chamber angles and intact irises, 10% phenylephrine eyedrops are very dangerous. Acute angle-closure glaucoma is readily produced and its control may require surgery. By contrast, in such eyes that have had a

PRIMARY ANGLE-CLOSURE GLAUCOMA peripheral or other iridectomy 10% phenylephrine drops are favored for producing pupil dilatation and preventing posterior synechiae. In 60 such eyes no angle closure occurred but one unfavorable outcome resulted from a coincidence of pupil dilatation with other factors. For eyes with shallow anterior chambers and intact irises, there is a danger in dilating pupils for examinations toward the end of consulting times because the wait for subsequent miosis tends to be too short and

419

acute angle-closure glaucoma is likely to develop. 82 Collins Street (C.l). A c KNOWLEDGMENTS

These investigations formed part of Research Project No. 14 of The Ophthalmic Research Institute of Australia and Project No. 13 of the Royal Victorian Eye and E a r Hospital. They were conducted in the Glaucoma Unit of the Hospital where the tonographies were performed by Dr. Magda Horvat. I wish to thank my colleagues for their co-operation in permitting examination of their patients and access to their records.

REFERENCES 1. Lowe, R. F. : Primary angle-closure glaucoma : Investigations after surgery for pupil block. Am. J. Ophth, 57 :931, 1964. 2. : Primary angle-closure glaucoma: Postoperative tests with 1-epinephrine base. Am. J. Ophth., 58 :S81, 1964. 3. Becker, B., Gage, T., Kolker, A. E., and Gay, A. J.: The effect of phenylephrine hydrochloride on the miotic treated eye. Am. J. Ophth.. 48 :313, 1959.

ECHOTHIOPHATE THE

EFFECT OF 0.0625%

JOSEPH

W.

WAHL,

IODIDE*

S O L U T I O N O N BLOOD C H O L I N E S T E R A S E

M.D.,

AND GEORGE

Denver,

This study was undertaken to learn the effect of topically applied 0.0625% echothiophate iodide (Phospholine Iodide) upon red blood cell and plasma cholinesterase. In an earlier report from this institution Humphreys and Holmes 1 demonstrated that the topical use of 0.25% echothiophate iodide produced a significant depression of red blood cell and plasma cholinesterase levels. At the present time the 0.0625% strength of echothiophate iodide is being used clinically in the treatment of glaucoma and accommodative esotropia. Therefore, it seemed important to determine the degree of cholinesterase depression produced by this medication. * From the Division of Ophthalmology, Department of Surgery, University of Colorado School of Medicine. The echothiophate iodide used in this study was provided through the courtesy of Campbell Pharmaceutical Company, New York.

S.

TYNER,

M.D.

Colorado

In 1957 echothiophate iodide (Phospholine Iodide) was introduced as a topical agent for the treatment of glaucoma. Later it was used for the treatment of accommodative esotropia. This drug belongs to the family of long-acting organic phosphorus anticholinesterase agents which include diisopropyl-flurophosphate (Floropryl) and demecarium bromide (Humorsol). 2 Echothiophate iodide is related to chemical compounds which were developed as war gases and insecticides. It is water soluble and highly stable, especially if refrigerated. It is an irreversible inhibitor of the enzyme cholinesterase. The normal function of cholinesterase in the body is the hydrolysis of acetylcholine which is found at all peripheral autonomie ganglia, all skeletal muscle myoneural junctions, all peripheral effector organs in the parasympathetic nervous system, and at the