ACTA O PHT HAL MO L OGICA VOL. 57 1979
Depnrtnirn~of Oplrthulvrology (Henri: J n n Ylteborg). Ullevdl Hospital, Univrrsit)) of Oslo
PILOCARPINE MEDICATION IN OPEN-ANGLE GLAUCOMA A Study Using Pilocarpine Eyedrops and an Ocular Therapeutic System BY
0. BRINCHMANN-HANSEN and N. ANMARKRUD
T w o modes of topical pilocarpine therapy were applied to sixteen patients with open-angle glaucoma. A pilocarpine drop medication (2 Oio solution four times daily) was compared to a constant and continuous supply of pilocarpine by a therapeutic delivery system (Ocusert P-40). T h e pressure reducing efficiency was studied in the morning and in the following four hour period of a n ordinary drop medication regimen. T h e results indicate about equal pressure reducing properties in both high and low pre-treatment pressure values. However, compared to pilocarpine drops, we found a statistically significant lower pressure in the morning after the Ocusert unit, especially in glaucomatous eyes with high pre-treatment pressure.
K e y words: open-angle glaucoma - pilocarpine pressure.
-
Ocusert
-
intraocular
For a century (from 1877) pilocarpine has been administered by eye-drop solutions to patients suffering from different kinds of glaucomas. In clinical usage, a topical instillation is applied to the glaucomatous eye in a pulsed manner of medication; usually four times daily during the waking hours of the patient. This mode of ocular self-medication has proved itself very useful in reducing the intraocular pressure. Failure to get a n expected pressure lowering response from drop medication could either be the result of inefficiency of the prescribed therapy, or it could be the result of poor patient compliance (Armaly X: Rao 1973). Received September 22, 1978.
55
0 . Brinchnionn-Hanscn and N . Anmorkrirrl An ocular therapeutic system (Ocusert P-40) worn in either the upper or lower cul-de-sac will supply a glaucomatous eye with pilocarpine molecules at a constant rate of 40 pg/h. This continuous release of drug has been shown to reduce the intraocular pressure substantially with less total amount of pilocarpine applied to the eye when compared with the pulsed dose medication (Armaly k Rao 1973). In the last few years, papers have been published comparing drops and membrane units with regard to dose-effect-relationship both in normal eyes (Place et al. 1975) and in hypertensiveiglaucomatous eyes (Armaly 8c Rao 1973; Macoul k Pavan-Langston 1975; Quigley et al. 1975). These works show that the membrane-controlled delivery system and the pilocarpine eyedrops achieved hypotensive results both in normal and open-angled glaucomatous patients. Quigley et al. (1975) found that a 40 pg/h unit controlled eyes requiring 2 O/O and 4 01’0 pilocarpine solutions four times daily. Other writers have been dealing with the Ocusert unit in other respects: patient compliance (Friederich 1974), side effects (less miosis and less myopia) (Brown et al. 1976) and 24 ‘h studies of effects of constant drug delivery to the glaucomatous eye (Armaly k Rao 1973). T h e purpose of this study was to compare the two modes of topical pilocarpine medication in open-angle glaucomas with regard to the pressure reducing efficiency. W e wanted to study the effect on the intraocular pressure in the morning at a time just before a glaucomatous eye would receive a pilocarpine drop. W e also wished to compare the effect on IOP during the following 4 h.
Material and Methods This study included sixteen patients with open-angle glaucoma; all of them had previously been treated with pilocarpine in drop solution, and all were responsive to this drug. They were free from external eye diseases, and none had undergone surgical eye intervention. All of them had earlier been diagnosed as having glaucoma. T h e patients were included based on following criteria: intraocular pressure equal to or greater than 22 mmHg measured by Goldmann applanation in the sitting position and glaucomatouv cupping of the optic disc with or without nerve fiber damage. A Haag-Streit lamp and mydriatics were used to reveal pseudoesfoliation of the lens capsule. All of the patients were examined just prior to the study. Pseudoexfoliation of the lens capsule was found in eight patients. There were 10 men and six women and the average age was 66 years (53-79). Number of eyes with glaucoma was 26. As a pre-study regimen five eyes used epinephrine (four patients), two eyes used acetazolamide (one patient) and five eyes used 56
P i l o c r i r ~ i n eMedication in Open-Angle Glnirconzn
epinephrine and acetazolamide (three patients). The patients who used epinephrine andior acetazolamide continued the same medication throughout the study. T h c mean pressure of three readings were used: no measure varying more than 3 mmHg from the others. T h e measurements were done by alternating between the patient’s right and left eye. Each patient was subjected to two experimental treatment sessions. Each session was preceded by a 44-48 h period, during which time any pilocarpine medication was discontinued. In the middle of this period the pressure was read a t 9 a. m. in order to establish pretreatment pressure values. In the one session the patients started a drop medication with one drop four times during one day (9 a. m., 1 p. in., 5 p. m. and 9 p. m.). T h e IOP was measured the next morning a t 9 a. m. After this reading, the patients were given by us one pilocarpine drop topically, and the IOP was again measured a t 11 a. m. and 1 p. ni. In the other session, on Ocusert unit was placed in either the upper or lower cul-de-sac at 9 a.m., and the IOP was measured the next morning a t the
28
T
Pre-treatment Pilocarpine drops Pilocarpineocusert
27 26 25 24
23 22 21 20 19 18 17
.,_ p c 0.01
pco.001
p c 0.001
4
Mean k
SEM
in 25 eyes at
I)
b
b
Fig. 1. a. m. Significant differences between treatments given by P-values.
57
0.Britichmrmii-llunscti und N . Aiiinurkrtrd same hour of the day. T h e patients continued wearing the unit, and the 101’ was again measured a t 1 1 a. m. and 1 p. m. T h e sequence of these sessions was randomly assigned for each patient.
Results All sixteen patients completed the study. They were well instructed how to replace the Ocusert unit in the lower cul-de-sac if the unit should fall out. W e started out with 26 eyes; five eyes lost the unit during the 24 h trial time. T h e unit were a t once replaced, with the exception of one eye; thus 25 eyes completed the study. The Student’s t-test (with P < 0.05) was used in the statistical calculations.
Ocusert P-40
Pilocarpine drops
9a.m.
1la.m.
1p.m.
18.8 17.5 1.03 0.84 3.57 2.92 i- n. s. -1 1-
18.33 0.75 2.61 n. s. -1
9a.m.
1la.m.
lp.m.
4 Group I Mean IOP 26 mm SI:M n = 12 Significance
Depnrtnirn~of Oplrthulvrology (Henri: J n n Ylteborg). Ullevdl Hospital, Univrrsit)) of Oslo
PILOCARPINE MEDICATION IN OPEN-ANGLE GLAUCOMA A Study Using Pilocarpine Eyedrops and an Ocular Therapeutic System BY
0. BRINCHMANN-HANSEN and N. ANMARKRUD
T w o modes of topical pilocarpine therapy were applied to sixteen patients with open-angle glaucoma. A pilocarpine drop medication (2 Oio solution four times daily) was compared to a constant and continuous supply of pilocarpine by a therapeutic delivery system (Ocusert P-40). T h e pressure reducing efficiency was studied in the morning and in the following four hour period of a n ordinary drop medication regimen. T h e results indicate about equal pressure reducing properties in both high and low pre-treatment pressure values. However, compared to pilocarpine drops, we found a statistically significant lower pressure in the morning after the Ocusert unit, especially in glaucomatous eyes with high pre-treatment pressure.
K e y words: open-angle glaucoma - pilocarpine pressure.
-
Ocusert
-
intraocular
For a century (from 1877) pilocarpine has been administered by eye-drop solutions to patients suffering from different kinds of glaucomas. In clinical usage, a topical instillation is applied to the glaucomatous eye in a pulsed manner of medication; usually four times daily during the waking hours of the patient. This mode of ocular self-medication has proved itself very useful in reducing the intraocular pressure. Failure to get a n expected pressure lowering response from drop medication could either be the result of inefficiency of the prescribed therapy, or it could be the result of poor patient compliance (Armaly X: Rao 1973). Received September 22, 1978.
55
0 . Brinchnionn-Hanscn and N . Anmorkrirrl An ocular therapeutic system (Ocusert P-40) worn in either the upper or lower cul-de-sac will supply a glaucomatous eye with pilocarpine molecules at a constant rate of 40 pg/h. This continuous release of drug has been shown to reduce the intraocular pressure substantially with less total amount of pilocarpine applied to the eye when compared with the pulsed dose medication (Armaly k Rao 1973). In the last few years, papers have been published comparing drops and membrane units with regard to dose-effect-relationship both in normal eyes (Place et al. 1975) and in hypertensiveiglaucomatous eyes (Armaly 8c Rao 1973; Macoul k Pavan-Langston 1975; Quigley et al. 1975). These works show that the membrane-controlled delivery system and the pilocarpine eyedrops achieved hypotensive results both in normal and open-angled glaucomatous patients. Quigley et al. (1975) found that a 40 pg/h unit controlled eyes requiring 2 O/O and 4 01’0 pilocarpine solutions four times daily. Other writers have been dealing with the Ocusert unit in other respects: patient compliance (Friederich 1974), side effects (less miosis and less myopia) (Brown et al. 1976) and 24 ‘h studies of effects of constant drug delivery to the glaucomatous eye (Armaly k Rao 1973). T h e purpose of this study was to compare the two modes of topical pilocarpine medication in open-angle glaucomas with regard to the pressure reducing efficiency. W e wanted to study the effect on the intraocular pressure in the morning at a time just before a glaucomatous eye would receive a pilocarpine drop. W e also wished to compare the effect on IOP during the following 4 h.
Material and Methods This study included sixteen patients with open-angle glaucoma; all of them had previously been treated with pilocarpine in drop solution, and all were responsive to this drug. They were free from external eye diseases, and none had undergone surgical eye intervention. All of them had earlier been diagnosed as having glaucoma. T h e patients were included based on following criteria: intraocular pressure equal to or greater than 22 mmHg measured by Goldmann applanation in the sitting position and glaucomatouv cupping of the optic disc with or without nerve fiber damage. A Haag-Streit lamp and mydriatics were used to reveal pseudoesfoliation of the lens capsule. All of the patients were examined just prior to the study. Pseudoexfoliation of the lens capsule was found in eight patients. There were 10 men and six women and the average age was 66 years (53-79). Number of eyes with glaucoma was 26. As a pre-study regimen five eyes used epinephrine (four patients), two eyes used acetazolamide (one patient) and five eyes used 56
P i l o c r i r ~ i n eMedication in Open-Angle Glnirconzn
epinephrine and acetazolamide (three patients). The patients who used epinephrine andior acetazolamide continued the same medication throughout the study. T h c mean pressure of three readings were used: no measure varying more than 3 mmHg from the others. T h e measurements were done by alternating between the patient’s right and left eye. Each patient was subjected to two experimental treatment sessions. Each session was preceded by a 44-48 h period, during which time any pilocarpine medication was discontinued. In the middle of this period the pressure was read a t 9 a. m. in order to establish pretreatment pressure values. In the one session the patients started a drop medication with one drop four times during one day (9 a. m., 1 p. in., 5 p. m. and 9 p. m.). T h e IOP was measured the next morning a t 9 a. m. After this reading, the patients were given by us one pilocarpine drop topically, and the IOP was again measured a t 11 a. m. and 1 p. ni. In the other session, on Ocusert unit was placed in either the upper or lower cul-de-sac at 9 a.m., and the IOP was measured the next morning a t the
28
T
Pre-treatment Pilocarpine drops Pilocarpineocusert
27 26 25 24
23 22 21 20 19 18 17
.,_ p c 0.01
pco.001
p c 0.001
4
Mean k
SEM
in 25 eyes at
I)
b
b
Fig. 1. a. m. Significant differences between treatments given by P-values.
57
0.Britichmrmii-llunscti und N . Aiiinurkrtrd same hour of the day. T h e patients continued wearing the unit, and the 101’ was again measured a t 1 1 a. m. and 1 p. m. T h e sequence of these sessions was randomly assigned for each patient.
Results All sixteen patients completed the study. They were well instructed how to replace the Ocusert unit in the lower cul-de-sac if the unit should fall out. W e started out with 26 eyes; five eyes lost the unit during the 24 h trial time. T h e unit were a t once replaced, with the exception of one eye; thus 25 eyes completed the study. The Student’s t-test (with P < 0.05) was used in the statistical calculations.
Ocusert P-40
Pilocarpine drops
9a.m.
1la.m.
1p.m.
18.8 17.5 1.03 0.84 3.57 2.92 i- n. s. -1 1-
18.33 0.75 2.61 n. s. -1
9a.m.
1la.m.
lp.m.
4 Group I Mean IOP 26 mm SI:M n = 12 Significance
