Norepinephrine in Treatment of Ocular Hypertension and Glaucoma Irvin P.
Pollack, MD,
Humberto
Rossi, MD
Norepinephrine (4%) as free base produced a significant fall in intraocular pressure and resistance to outflow. This effect was sustained for up to 20 weeks. No significant difference could be shown between the effect of 2%, 3%, and 4% norepinephrine on the aqueous humor dynamics. The effect on pressure and facility was shown in eyes with ocular hypertension and with glaucoma. An additive effect was observed after use of norepinephrine with pilocarpine in the rine has
the treatment of glaucoma. Crossover studies between epinephrine borate 1% and norepinephrine borate 4% revealed no significant difference. Like epineph-
rine, norepinephrine produces a conjunctival hyperemia in many patients. However, there is an absence of tachycardia after use of norepinephrine, and one person in this study showed an allergic reaction to epinephrine that cleared promptly and completely when norepinephrine was substituted.
expressed
the free
epineph¬ Duringtopicalpastenjoyed antiglaucoma agent.
be
structurally epinephrine (Fig 1), the levorotatary norepinephrine might be expected to provide a similar pressure-lowering effect. Studies with 2% norepineph¬
Ocular Hypertension and Previously Un¬ treated Glaucoma.—Fifteen persons were studied with regard to the effect of 3% and 4% norepinephrine borate on the aqueous
15 years wide clinical
use as a
Because it is
similar to
rine free base have shown that al¬ though the drug frequently causes no significant change in intraocular pressure (IOP) in persons with nor¬ mal IOP, it does produce a significant pressure reduction in individuals with ocular hypertension.1 Until recently, the clinical use¬ fulness of norepinephrine has been largely limited because of its insta¬ bility, but recent pharmacologie ad¬ vances have made it possible to pro¬ duce a more stable preparation. For this reason and because previous studies have indicated a dose-re¬ sponse relationship,' it seemed logical -
·
to expand our previous investigations to include 3% and 4% concentrations
of
norepinephrine
ther references to
free base. (All fur¬ norepinephrine will
Submitted for publication Nov 28, 1973. From the Johns Hopkins University School of Medicine, the Wilmer Institute, Baltimore. Reprint requests to the Wilmer Institute, Johns Hopkins University School of Medicine, 601 N Broadway, Baltimore, MD 21205 (Dr.
Pollack).
as
base.)
Methods
humor dynamics. All of the individuals had ocular hypertension or previously undiagnosed primary open-angle glaucoma and had used no glaucoma medication for four weeks prior to the time they were ad¬ mitted to the study. They were originally seen in the general clinic of the Wilmer In¬ stitute, Baltimore, before being referred to the glaucoma service for evaluation. Each person was then given a complete ocular examination, including measure¬ ment of the visual acuity, ophthalmoscopy, biomicroscopy, Goldmann applanation tonometry, measurement of the horizontal diameter of the pupils using the telescopic device of the Goldmann perimeter, visualfield examination with the Goldmann pe¬ rimeter, and tonography. Each patient was asked to return for repeat measurements of the visual acuity, pupil diameter, and applanation tonometry. Base-line values for IOP were determined by taking the mean of the results of these two pre¬ treatment examinations. The patients were then seen twice weekly for two weeks. At each visit, the tests were re¬ peated, with the exception of tonography, which was repeated only during the last visit. With few exceptions, all patients were seen between 12 pm and 2 pm.
Open-Angle
Glaucoma
Previously
Treated.—Six persons were studied to de¬ termine the effect on aqueous humor dy¬ namics that was obtained when norepi¬ nephrine was added to the regimen of individuals already being treated with pilocarpine. In each case, the patient had gonioscopically open angles and glaucomatous disc and field changes and was al¬ ready being treated with no other glau¬ coma medication except pilocarpine 4% four times daily in each eye. Following the two base-line visits as described, each indi¬ vidual was instructed to use norepineph¬ rine 4% twice daily in one randomly se¬ lected eye. The patients were then seen twice weekly for two weeks in the manner described above. Crossover Study.—Five persons were in¬ structed to use epinephrine 1% free base in one eye twice daily and 4% norepinephrine in the other eye twice daily. (All further references to epinephrine will be expressed as free base.) Each patient was seen twice weekly for two weeks, at the end of which time he was asked to reverse the treat¬ ment and use the norepinephine in the eye previously treated with epinephrine and the epinephrine in the eye previously treated with norepinephrine. The patients were again seen twice weekly for two weeks before concluding this segment of the study. Side
Effects.—Twenty-eight persons were OH
0'
,0H
CHOH I
CH2 I NH2
Epinephrine
Fig 1.—Epinephrine and norepinephrine structurally similar.
are
Downloaded From: http://archopht.jamanetwork.com/ by a Monash University Library User on 06/03/2015
Norepinephrine
Base-line pressure in treated eye, 23
26
26
23
mm
31
29
Hg 31
33
Percent change in tr/P—,
Fig 2.—Effect of norepinephrine borate 4% on IOP. Base-line IOP for each of nine eyes is shown on abscissa and correspond¬ ing change in applanation pressure (solid lines) is read from left Table 1.—Effect of
Norepinephrine 4%
on
T,
1
26 29.5 33 23 26 31 31 36 23.5
*
_C, 26 23 29 19 21 30 31 23 20.5
After
were
Percent
,/C,
T2
C2
T2/C2
1.0 1.28 1.14 1.21 1.24 1.03 1.0 1.57 1.15
24 23.5 24 20 22 25 24 30 20
30 23.5 31 22 24 27 31 23 20
0.8 1.0 0.77 0.91 0.92 0.92 0.77 1.30 1.0
Change (T/C) -20 -21 -33 -25 -26
-23 -17 -13
Treated eye; intraocular pressure (mm Hg) before (TT) or after (T2) treatment with norepinephrine 4%. Each figure represents a mean of two readings taken three days apart. C = Control eye (mm Hg). =
investigated for possible side effects when using norepinephrine, ten of whom were asked to use 1% epinephrine in one eye and 3% or 4% norepinephrine in the fellow eye. At the end of the period of investigation lasting from 4 to 20 weeks, each eye was evaluated for hyperemia, papillary or follicular hypertrophy of the tarsal and palpebrai conjunctiva, and fluoresceinstaining of the cornea. Twelve persons observed for 4 to 20 weeks while using 3% or 4% norepinephrine in one eye only and were evaluated at the end of the study period in the same manner. Six additional persons who underwent a similar study were being treated with 4% pilocarpine in both eyes four times daily along with 4% norepinephrine in one eye twice daily. All patients were examined by the same examiner and in no case did he know which eye was being treated with which drug. were
Results
Hypertension Patients.—In each of the nine persons who were asked to instill 4% norepinephrine in one eye twice daily there occurred a fall in the IOP ranging from 2 to 9 mm Hg (Fig 2, solid lines). The data were better analyzed by taking into Ocular
account any
in both eyes twice daily followed at monthly intervals for 20 weeks. Figure 3 shows that the mean base-line IOP in the eight treated eyes fell from 27 mm Hg to 21 mm Hg one week after treatment and remained between 21 mm Hg and 23 mm Hg throughout the period of
nephrine
Applanation Tonometry*
Before Patient
ordinate. For each eye, percent change in ratio of IOP in treated/control eye is shown as interrupted line and read from right ordinate.
spontaneous pressure
changes occurring in the untreated fellow (control) eye. This was done by comparing the pretreatment IOP ra¬ tio of the treated/control eye (Table 1, ,/CO with the same ratio after treatment (T2/C2). The results indi¬ cate a fall in this ratio ranging from 11% to 33%. Four persons using 4% norepineph¬ rine in one eye twice daily and two additional persons using 4% norepi-
Downloaded From: http://archopht.jamanetwork.com/ by a Monash University Library User on 06/03/2015
follow-up.
A similar study was made with 3% norepinephrine, and with this concen¬ tration, there occurred a fall in the
IOP ratio of the treated/control eye 8% to 25% (Table 2). The effect of 4% norepinephrine on the facility of aqueous outflow is shown in Fig 4. In every case, there was an increase in the ratio of the outflow facility in the treated/control eye (Table 3).
ranging from
Open-Angle Glaucoma Patients.— Five of the six persons who were pre¬ viously treated with 4% pilocarpine showed a further decrease in the IOP after 4% norepinephrine was added to the regimen in one eye only (Table 4). This represented a mean fall in the IOP ratio in the treated/control eye of 13% and was significant at the 5% level of confidence. Crossover Study.—Five persons were asked to use 1% epinephrine free base in one eye and 4% norepinephrine in the second eye for two weeks before reversing the therapy for another two weeks. These results indicate that there was no significant effect on the mean IOP when epinephrine and
351-
30
25
s co co
20
d)
15
I I I -1 0+1
_L J_ 4 +12 +8 + Weeks after treatment
+ 16
+20
effect of norepinephrine 4% on IOP. Each point on graph represents Prior to treatment, each patient was seen for control studies occasions with an Interval of four to seven days. After treatment with 4%, mean IOP fell significantly and remained at this level for duration of
Fig 3—Long-term
eight eyes.
mean ±SD for on two separate
norepinephrine study.
Table 2.—Effect of
Norepinephrine 3%
on
Applanation Tonometry
After Before ,-*-, ,-»-,
Percent
Change
(T/C) T,_C,_ ,/C,_T¡_Cj_T2/C2 1_32_26_Ì2_18_20_OjK)_—25
Patient
2_27_28_0j!6_22_25_0JÎ8_- 8 3_27_29_5_0J31_19_24_ 79_-13
4_34_2^5_U5_22j>_24_0J34_-18 5_25J5_21_^2_19J5_18_U_- 8 6
33.5
norepinephrine (Table 5).
discontinued, and the blepharitis cleared within three days with no medica¬ tions except carbachol. It was ultimately necessary to switch first to echothiophate iodide 0.125% in each eye twice daily and later to demecarium bromide 0.25% in each eye twice daily before satisfactory pres¬ sure control was obtained. In March 1973, she was asked to use 2% norepinephrine in the right eye twice daily and 1% epinephryl borate (Eppy) in the left eye twice daily in addition to demecarium bromide 0.25% in each eye twice daily. Three days later, she developed moderate conjunctival hyper¬ emia and severe itching and tearing of the left eye along with moderate edema of the left upper and lower eyelids. She was asked to discontinue the epinephryl borate and use the norepinephrine in both eyes twice daily. No other medications were prescribed except for demecarium bromide 0.25% in each eye twice daily. Within four days the itching had com¬ pletely gone, swelling had regressed, and the patient was asymptomatic. She was in¬ structed to once again resume use of 1% epinephryl borate in the left eye, 2% nor¬ epinephrine in the right eye, and -deme¬ carium bromide 0.25% in both eyes, twice daily. Two days later, she called in great distress because of intolerable itching and tearing in the left, epinephrine-treated eye. The patient stated that she could not open the left eye. She was seen two hours later, by which time she could open the left eye, but there was still severe itching, tearing, and moderate edema of the left upper and lower eyelids. The right eye ap¬ peared normal (Fig 5, left). The patient was told to once again discontinue using epinephryl borate in the left eye and to resume use of norepinephrine 2% in both eyes twice daily along with the demecar¬ ium bromide. Within 24 hours, there was marked improvement, and in three days, there was no further itching, tearing, or edema (Fig 5, right). Throughout this time, the IOP remained well controlled. Each of the persons treated with norepi¬ nephrine in one eye and epinephrine in the second eye were asked for their subjective impression regarding which eye felt more comfortable. Five out of ten persons indi¬ cated that the norepinephrine-treated eye was more comfortable. Two of these had no ocular hyperemia in either eye, whereas one had an equal amount of ocular hyper¬ emia in each eye, and one patient showed pupillary hypertrophy and increased hy¬ peremia of the palpebrai conjunctiva in the was
24.5
were
1.4
interchanged
Side-Effects.—Ten persons received 3% and 4% norepinephrine in one eye and 1% epinephrine in the fellow eye. Four persons showed no ocular hyperemia in either the epinephrine- or norepinephrine-treated eye. In four cases, there was an equal amount of redness in both eyes. In one case, there was an equal amount of bulbar conjunctival hyperemia, but the epinephrine-treated eye showed much more hyperemia of the palpebrai conjunctiva, even though the nor¬ epinephrine-treated eye had been treated with norepinephrine four weeks longer than the fellow eye had been treated with epinephrine. In the
30.5
28
1.1
-21
same case, there was papillary hyper¬ trophy of the tarsal conjunctiva in the epinephrine-treated eye only. One patient developed an allergic response to epinephrine on two occa¬ sions but not to norepinephrine when it was substituted for the epineph¬
rine. This is described in the follow¬
ing
report. Report of a Case A 75-year-old white woman had a year history of open-angle glaucoma case
ten-
that was controlled with carbachol 1.5% four times daily until December 1969 when she was asked to start using epinephrine hy¬ drochloride (Glaucon) 2% in each eye at bedtime. Five weeks later, she was seen as an emergency because of severe blepha¬ ritis, ocular redness, and itching. Glaucon
epinephrine-treated
Downloaded From: http://archopht.jamanetwork.com/ by a Monash University Library User on 06/03/2015
eye.
Comment
When 3% and 4%
norepinephrine
240
Table 5.—Crossover
-220
Patient 1
¿200 C? 180 160
~
0)
? co
140
o
120
Mean
60 40 20.06
.06
.08
.08
.14
.16
Base-line
facility
Fig 4.—Effect of norepinephrine borate 4% on facility of aqueous outflow. Base-line fa¬ cility of aqueous outflow in eye to be treated of six individuals is shown on abscissa. Per¬ centage change in ratio of base-line facility in eye to be treated to that of control eye is shown on ordinate axis. In each case, there occurred an increase in ratio following topi¬ cal instillation of norepinephrine 4%.
Table 3.—Effect of
Norepinephrine 4%
on
Before
Facility of Aqueous Outflow* After
Percent
Patient
T,
C,
,/C,
T2
C2
T2/C2
Change (T/C)
1
.14
.24 .31 .09 .15 .12 .10
.58 .52 .67 .53 .50 .80
.23 .20 .13 .14 .09 .15
.17 .19 .14 .08
1.35 1.05 .93 1.75 .90 1.25
+133 +102 + 39 +230 + 80 + 56
.06 .08 .06 .08 =
25 24 24 21.4
24 24 30 22.2
15 20 24 26 23
22.6
Treated 4%
eye,
—>
t—'
.10 .12
facility of outflow before (T,) and after (T2)
(µ /min/mm Hg).
C
=
Control eye
treatment with
(µ, /min/mm Hg).
norepi¬
=
Table 4.—Additive Effect of Norepinephrine 4% on Persons Being Treated With Pilocarpine 4%
=
*
Before Patient 1
T, (P4)
Ci (P4)
,/C,
32 27 23
27 32 19 23 24 24
1.17 .86 1.22 .82 1.0 1.08
19 24 26
=
After
T2 (P4 + NE4) C2 (P4) 32 21 15 12 20 22
31 30 19 14 22 21
Percent
T2/C2 1.03 .68 .81 .86 .91 1.02
Change (T/C) -.12 —.20 -.34
+.05 -.09 -.06
= Treated eye; before (T,) or after (T2) treatment with norepinephrine 4% (mm Hg). Each result represents mean of two readings taken three days apart. C = Control eye (mm Hg). Each result represents mean of two readings taken three days apart. Percent change mean ± SD (P
Pollack, MD,
Humberto
Rossi, MD
Norepinephrine (4%) as free base produced a significant fall in intraocular pressure and resistance to outflow. This effect was sustained for up to 20 weeks. No significant difference could be shown between the effect of 2%, 3%, and 4% norepinephrine on the aqueous humor dynamics. The effect on pressure and facility was shown in eyes with ocular hypertension and with glaucoma. An additive effect was observed after use of norepinephrine with pilocarpine in the rine has
the treatment of glaucoma. Crossover studies between epinephrine borate 1% and norepinephrine borate 4% revealed no significant difference. Like epineph-
rine, norepinephrine produces a conjunctival hyperemia in many patients. However, there is an absence of tachycardia after use of norepinephrine, and one person in this study showed an allergic reaction to epinephrine that cleared promptly and completely when norepinephrine was substituted.
expressed
the free
epineph¬ Duringtopicalpastenjoyed antiglaucoma agent.
be
structurally epinephrine (Fig 1), the levorotatary norepinephrine might be expected to provide a similar pressure-lowering effect. Studies with 2% norepineph¬
Ocular Hypertension and Previously Un¬ treated Glaucoma.—Fifteen persons were studied with regard to the effect of 3% and 4% norepinephrine borate on the aqueous
15 years wide clinical
use as a
Because it is
similar to
rine free base have shown that al¬ though the drug frequently causes no significant change in intraocular pressure (IOP) in persons with nor¬ mal IOP, it does produce a significant pressure reduction in individuals with ocular hypertension.1 Until recently, the clinical use¬ fulness of norepinephrine has been largely limited because of its insta¬ bility, but recent pharmacologie ad¬ vances have made it possible to pro¬ duce a more stable preparation. For this reason and because previous studies have indicated a dose-re¬ sponse relationship,' it seemed logical -
·
to expand our previous investigations to include 3% and 4% concentrations
of
norepinephrine
ther references to
free base. (All fur¬ norepinephrine will
Submitted for publication Nov 28, 1973. From the Johns Hopkins University School of Medicine, the Wilmer Institute, Baltimore. Reprint requests to the Wilmer Institute, Johns Hopkins University School of Medicine, 601 N Broadway, Baltimore, MD 21205 (Dr.
Pollack).
as
base.)
Methods
humor dynamics. All of the individuals had ocular hypertension or previously undiagnosed primary open-angle glaucoma and had used no glaucoma medication for four weeks prior to the time they were ad¬ mitted to the study. They were originally seen in the general clinic of the Wilmer In¬ stitute, Baltimore, before being referred to the glaucoma service for evaluation. Each person was then given a complete ocular examination, including measure¬ ment of the visual acuity, ophthalmoscopy, biomicroscopy, Goldmann applanation tonometry, measurement of the horizontal diameter of the pupils using the telescopic device of the Goldmann perimeter, visualfield examination with the Goldmann pe¬ rimeter, and tonography. Each patient was asked to return for repeat measurements of the visual acuity, pupil diameter, and applanation tonometry. Base-line values for IOP were determined by taking the mean of the results of these two pre¬ treatment examinations. The patients were then seen twice weekly for two weeks. At each visit, the tests were re¬ peated, with the exception of tonography, which was repeated only during the last visit. With few exceptions, all patients were seen between 12 pm and 2 pm.
Open-Angle
Glaucoma
Previously
Treated.—Six persons were studied to de¬ termine the effect on aqueous humor dy¬ namics that was obtained when norepi¬ nephrine was added to the regimen of individuals already being treated with pilocarpine. In each case, the patient had gonioscopically open angles and glaucomatous disc and field changes and was al¬ ready being treated with no other glau¬ coma medication except pilocarpine 4% four times daily in each eye. Following the two base-line visits as described, each indi¬ vidual was instructed to use norepineph¬ rine 4% twice daily in one randomly se¬ lected eye. The patients were then seen twice weekly for two weeks in the manner described above. Crossover Study.—Five persons were in¬ structed to use epinephrine 1% free base in one eye twice daily and 4% norepinephrine in the other eye twice daily. (All further references to epinephrine will be expressed as free base.) Each patient was seen twice weekly for two weeks, at the end of which time he was asked to reverse the treat¬ ment and use the norepinephine in the eye previously treated with epinephrine and the epinephrine in the eye previously treated with norepinephrine. The patients were again seen twice weekly for two weeks before concluding this segment of the study. Side
Effects.—Twenty-eight persons were OH
0'
,0H
CHOH I
CH2 I NH2
Epinephrine
Fig 1.—Epinephrine and norepinephrine structurally similar.
are
Downloaded From: http://archopht.jamanetwork.com/ by a Monash University Library User on 06/03/2015
Norepinephrine
Base-line pressure in treated eye, 23
26
26
23
mm
31
29
Hg 31
33
Percent change in tr/P—,
Fig 2.—Effect of norepinephrine borate 4% on IOP. Base-line IOP for each of nine eyes is shown on abscissa and correspond¬ ing change in applanation pressure (solid lines) is read from left Table 1.—Effect of
Norepinephrine 4%
on
T,
1
26 29.5 33 23 26 31 31 36 23.5
*
_C, 26 23 29 19 21 30 31 23 20.5
After
were
Percent
,/C,
T2
C2
T2/C2
1.0 1.28 1.14 1.21 1.24 1.03 1.0 1.57 1.15
24 23.5 24 20 22 25 24 30 20
30 23.5 31 22 24 27 31 23 20
0.8 1.0 0.77 0.91 0.92 0.92 0.77 1.30 1.0
Change (T/C) -20 -21 -33 -25 -26
-23 -17 -13
Treated eye; intraocular pressure (mm Hg) before (TT) or after (T2) treatment with norepinephrine 4%. Each figure represents a mean of two readings taken three days apart. C = Control eye (mm Hg). =
investigated for possible side effects when using norepinephrine, ten of whom were asked to use 1% epinephrine in one eye and 3% or 4% norepinephrine in the fellow eye. At the end of the period of investigation lasting from 4 to 20 weeks, each eye was evaluated for hyperemia, papillary or follicular hypertrophy of the tarsal and palpebrai conjunctiva, and fluoresceinstaining of the cornea. Twelve persons observed for 4 to 20 weeks while using 3% or 4% norepinephrine in one eye only and were evaluated at the end of the study period in the same manner. Six additional persons who underwent a similar study were being treated with 4% pilocarpine in both eyes four times daily along with 4% norepinephrine in one eye twice daily. All patients were examined by the same examiner and in no case did he know which eye was being treated with which drug. were
Results
Hypertension Patients.—In each of the nine persons who were asked to instill 4% norepinephrine in one eye twice daily there occurred a fall in the IOP ranging from 2 to 9 mm Hg (Fig 2, solid lines). The data were better analyzed by taking into Ocular
account any
in both eyes twice daily followed at monthly intervals for 20 weeks. Figure 3 shows that the mean base-line IOP in the eight treated eyes fell from 27 mm Hg to 21 mm Hg one week after treatment and remained between 21 mm Hg and 23 mm Hg throughout the period of
nephrine
Applanation Tonometry*
Before Patient
ordinate. For each eye, percent change in ratio of IOP in treated/control eye is shown as interrupted line and read from right ordinate.
spontaneous pressure
changes occurring in the untreated fellow (control) eye. This was done by comparing the pretreatment IOP ra¬ tio of the treated/control eye (Table 1, ,/CO with the same ratio after treatment (T2/C2). The results indi¬ cate a fall in this ratio ranging from 11% to 33%. Four persons using 4% norepineph¬ rine in one eye twice daily and two additional persons using 4% norepi-
Downloaded From: http://archopht.jamanetwork.com/ by a Monash University Library User on 06/03/2015
follow-up.
A similar study was made with 3% norepinephrine, and with this concen¬ tration, there occurred a fall in the
IOP ratio of the treated/control eye 8% to 25% (Table 2). The effect of 4% norepinephrine on the facility of aqueous outflow is shown in Fig 4. In every case, there was an increase in the ratio of the outflow facility in the treated/control eye (Table 3).
ranging from
Open-Angle Glaucoma Patients.— Five of the six persons who were pre¬ viously treated with 4% pilocarpine showed a further decrease in the IOP after 4% norepinephrine was added to the regimen in one eye only (Table 4). This represented a mean fall in the IOP ratio in the treated/control eye of 13% and was significant at the 5% level of confidence. Crossover Study.—Five persons were asked to use 1% epinephrine free base in one eye and 4% norepinephrine in the second eye for two weeks before reversing the therapy for another two weeks. These results indicate that there was no significant effect on the mean IOP when epinephrine and
351-
30
25
s co co
20
d)
15
I I I -1 0+1
_L J_ 4 +12 +8 + Weeks after treatment
+ 16
+20
effect of norepinephrine 4% on IOP. Each point on graph represents Prior to treatment, each patient was seen for control studies occasions with an Interval of four to seven days. After treatment with 4%, mean IOP fell significantly and remained at this level for duration of
Fig 3—Long-term
eight eyes.
mean ±SD for on two separate
norepinephrine study.
Table 2.—Effect of
Norepinephrine 3%
on
Applanation Tonometry
After Before ,-*-, ,-»-,
Percent
Change
(T/C) T,_C,_ ,/C,_T¡_Cj_T2/C2 1_32_26_Ì2_18_20_OjK)_—25
Patient
2_27_28_0j!6_22_25_0JÎ8_- 8 3_27_29_5_0J31_19_24_ 79_-13
4_34_2^5_U5_22j>_24_0J34_-18 5_25J5_21_^2_19J5_18_U_- 8 6
33.5
norepinephrine (Table 5).
discontinued, and the blepharitis cleared within three days with no medica¬ tions except carbachol. It was ultimately necessary to switch first to echothiophate iodide 0.125% in each eye twice daily and later to demecarium bromide 0.25% in each eye twice daily before satisfactory pres¬ sure control was obtained. In March 1973, she was asked to use 2% norepinephrine in the right eye twice daily and 1% epinephryl borate (Eppy) in the left eye twice daily in addition to demecarium bromide 0.25% in each eye twice daily. Three days later, she developed moderate conjunctival hyper¬ emia and severe itching and tearing of the left eye along with moderate edema of the left upper and lower eyelids. She was asked to discontinue the epinephryl borate and use the norepinephrine in both eyes twice daily. No other medications were prescribed except for demecarium bromide 0.25% in each eye twice daily. Within four days the itching had com¬ pletely gone, swelling had regressed, and the patient was asymptomatic. She was in¬ structed to once again resume use of 1% epinephryl borate in the left eye, 2% nor¬ epinephrine in the right eye, and -deme¬ carium bromide 0.25% in both eyes, twice daily. Two days later, she called in great distress because of intolerable itching and tearing in the left, epinephrine-treated eye. The patient stated that she could not open the left eye. She was seen two hours later, by which time she could open the left eye, but there was still severe itching, tearing, and moderate edema of the left upper and lower eyelids. The right eye ap¬ peared normal (Fig 5, left). The patient was told to once again discontinue using epinephryl borate in the left eye and to resume use of norepinephrine 2% in both eyes twice daily along with the demecar¬ ium bromide. Within 24 hours, there was marked improvement, and in three days, there was no further itching, tearing, or edema (Fig 5, right). Throughout this time, the IOP remained well controlled. Each of the persons treated with norepi¬ nephrine in one eye and epinephrine in the second eye were asked for their subjective impression regarding which eye felt more comfortable. Five out of ten persons indi¬ cated that the norepinephrine-treated eye was more comfortable. Two of these had no ocular hyperemia in either eye, whereas one had an equal amount of ocular hyper¬ emia in each eye, and one patient showed pupillary hypertrophy and increased hy¬ peremia of the palpebrai conjunctiva in the was
24.5
were
1.4
interchanged
Side-Effects.—Ten persons received 3% and 4% norepinephrine in one eye and 1% epinephrine in the fellow eye. Four persons showed no ocular hyperemia in either the epinephrine- or norepinephrine-treated eye. In four cases, there was an equal amount of redness in both eyes. In one case, there was an equal amount of bulbar conjunctival hyperemia, but the epinephrine-treated eye showed much more hyperemia of the palpebrai conjunctiva, even though the nor¬ epinephrine-treated eye had been treated with norepinephrine four weeks longer than the fellow eye had been treated with epinephrine. In the
30.5
28
1.1
-21
same case, there was papillary hyper¬ trophy of the tarsal conjunctiva in the epinephrine-treated eye only. One patient developed an allergic response to epinephrine on two occa¬ sions but not to norepinephrine when it was substituted for the epineph¬
rine. This is described in the follow¬
ing
report. Report of a Case A 75-year-old white woman had a year history of open-angle glaucoma case
ten-
that was controlled with carbachol 1.5% four times daily until December 1969 when she was asked to start using epinephrine hy¬ drochloride (Glaucon) 2% in each eye at bedtime. Five weeks later, she was seen as an emergency because of severe blepha¬ ritis, ocular redness, and itching. Glaucon
epinephrine-treated
Downloaded From: http://archopht.jamanetwork.com/ by a Monash University Library User on 06/03/2015
eye.
Comment
When 3% and 4%
norepinephrine
240
Table 5.—Crossover
-220
Patient 1
¿200 C? 180 160
~
0)
? co
140
o
120
Mean
60 40 20.06
.06
.08
.08
.14
.16
Base-line
facility
Fig 4.—Effect of norepinephrine borate 4% on facility of aqueous outflow. Base-line fa¬ cility of aqueous outflow in eye to be treated of six individuals is shown on abscissa. Per¬ centage change in ratio of base-line facility in eye to be treated to that of control eye is shown on ordinate axis. In each case, there occurred an increase in ratio following topi¬ cal instillation of norepinephrine 4%.
Table 3.—Effect of
Norepinephrine 4%
on
Before
Facility of Aqueous Outflow* After
Percent
Patient
T,
C,
,/C,
T2
C2
T2/C2
Change (T/C)
1
.14
.24 .31 .09 .15 .12 .10
.58 .52 .67 .53 .50 .80
.23 .20 .13 .14 .09 .15
.17 .19 .14 .08
1.35 1.05 .93 1.75 .90 1.25
+133 +102 + 39 +230 + 80 + 56
.06 .08 .06 .08 =
25 24 24 21.4
24 24 30 22.2
15 20 24 26 23
22.6
Treated 4%
eye,
—>
t—'
.10 .12
facility of outflow before (T,) and after (T2)
(µ /min/mm Hg).
C
=
Control eye
treatment with
(µ, /min/mm Hg).
norepi¬
=
Table 4.—Additive Effect of Norepinephrine 4% on Persons Being Treated With Pilocarpine 4%
=
*
Before Patient 1
T, (P4)
Ci (P4)
,/C,
32 27 23
27 32 19 23 24 24
1.17 .86 1.22 .82 1.0 1.08
19 24 26
=
After
T2 (P4 + NE4) C2 (P4) 32 21 15 12 20 22
31 30 19 14 22 21
Percent
T2/C2 1.03 .68 .81 .86 .91 1.02
Change (T/C) -.12 —.20 -.34
+.05 -.09 -.06
= Treated eye; before (T,) or after (T2) treatment with norepinephrine 4% (mm Hg). Each result represents mean of two readings taken three days apart. C = Control eye (mm Hg). Each result represents mean of two readings taken three days apart. Percent change mean ± SD (P
