A double-masked comparison of betaxolol and levobunolol for the treatment of primary open-angle glaucoma

&te artigo mostra os resultados de um estudo duplo-cego entre betaxolol solução oftálmica a 0,5% e levobunolol solução oftálmica a 0,5% em 40 pacientes g1aucomatosos. Vinte (20) pacientes, ao acaso, receberam betaxolol e outros vinte (20) pacientes foram, aleatoriamente, selecionados para o tratamen­ to com levobunolol. O trabalho desenvolveu-se durante 12 semanas, nas quais os efei­ tos das drogas mencionadas foram obervados, especialmente sobre a pressã o intra-ocular, bem como seus poss íveis efeitos sistêmicos.


INTRODUCI10N
The introduction of topical beta adrenergic blocking agents has im proved the treatment of Glaucoma, showing its effectiveness in reducing the intra-ocular pressure.However, non selective adrenergic beta-bloc kers may often cause adverse reac tions, specially in the respirato ry ( 3 ,6 . 12 ), .cardiovasculw:( 1 6 ) and cen tral nervous systems( 1 7).
Evaluation of agents that would provide ocular hypotensive activity and reduced systemic side effects .

PATIENTS AND METHODS
. This study was a twelve-week double-masked, randomized, paral child-bearing potencial not using adequate contraceptive methods.Further, patients could be declared ineligible for any sound medical rea sono Signed informed consent was obtained from patients meeting the enrollment criteria.Following en rollment, patients were randomly as signed in equal numbers to either the Betaxolol or Levobunolol treatment groups.
A pretherapy examination was administered and the fo llowing data were recorded: demographic infor mation, medical history , visual acuity , pupillary diameter, perimetry, intraocular pressure, ocular signs and symptoms (slit-lamp biomicros copy), cup/disc ratios, resting pulse rate and blood pressure.Baseline pa rameters were repeated at weeks I, 2, 4, 8 and 12 except for perimetry and fundus examinations which were conducted only at the 12 week exa mination.
The test medications were then dispensed to the patients, who were instructed to administer the eye drops in the affected eyes every 12 hours.No adjunctive glaucoma the rapy was allowed during the study.However, the investigator could re move any patient from the study if intraocular pressure was not conside red to be well controlled by the study medication.
Analyses of variance were used to compare 0.25% Betaxolol Suspen sion versus 0.5% Betaxolol Solution at 8 hours and at 12 hours after do sing with respect to changes from baseline in intraocular pressure pulse rate, and mean arterial pressure.Pa tient comments referring to burning, stinging and perceived changes in the discomfort scale upon instillation of the eye drops were combined and considered as "ocular discomfort".Inc1uded in this category were re ports of discomfort considered rela ted, possibly related, and not related to the study medication.Chi-square was used to test for differences bet ween the two treatments in the inci dence of ocular discomfort and blur red visiono A double-masked comparison of betaxo/ol and levobuno/ol fo r the treatment of primary op en-angle glaucoma Data were submitted to statystical analysis.Tables and figures show average and standard errors ; F Test (Fisher) was used for simple corre lation of nonpaired data; two-way analysis of variance was used for multiple correlation.
When indicated by the F Test, correlation between averages was established through the LSD (Least Significant Differences) method.

DATA AND RESULTS (BETAXOLOL)
Perimetry: 15 out of the 20 patients presented normal visual field, 3 with visual field loss in both eyes, and 2 patients presented visual field loss in one of the eyes.
Visual field was examined at pre-therapy phase and at the end treatment on the 12th week.
No changes were observed in 19 patients; one patient however, pa tient number 7 of this study, who had non-diagnosed glaucoma with a very high pressure in both eyes, showed a marked improvement in his visual field after 10 wering IOP due to medication.
Intraocular Pressure: IOP average in mmHg in 39 eyes, verified in the pretherapy phase and in the fo lio wing examinations are shown below.We can verify an improvement in circulation conditions at optical ner ve leveI.
Pupill ary Diameter: Measured on pre-therapy phase and on the fo llo wing examinations it has not shown any alterations in its size.The 20 patients presented ocular buring.ln 12 of them the symptoms were weak (1) with improvement du ring the treatment.8 patients pre sented moderate buming symptoms (2) while 3 patients improved to weak (1) and 5 of them remained unaltered.

Ocular Signs
No visible ocular modifications were observed during the treatment.

Systemic Alterations
There were DO alterations on a general leveI.We would like to point out that 4 of the patients included in this group showed steady bronchial asthma and were using Timolol Ma leate 0.5%, 2 times/day to control Glaucoma.
They were presenting chest squeaking sometimes and low inten se dyspneia.With the switch to De-ARQ.BRAS.OFrAL.53(1), 1990 A double-mosked compariaon of beraxolol and levobunolol fo r the treatment of primary op en-angle glaucoma taxolol drops they did not present the above described symptoms any more.Pupill ary Diameter: There .was no change on pupillary size with the use of the drug.
Fundos Examination: The were no alterations as to retina and optical nerve leveI along the oberved pc riod.
LocaI signs: We have not observed any different ocular signs.
with improveroent noted in 40% of the patients.There were no clinical significant differences observed bt ween the treatment groups in the other symptoms evaluated.PuImonary System: No pulmonary changes were observed in lhe two groups, even for patients with chro nic asthma that received Betaxolol.
Betaxolol is indicated for the treatment of all patients who need to control IOP.For its efficacy and sa fety on possible side effects, Beta-ARQ.BRAS.OFrAL.53(1), 1990 lel-group comparison of Betaxolol 0,5% Ophthalmic Solution versus Lebobunolol 0,5% Ophthalmic So lution with forty (40) primary open angle glaucoma patients participating in the clínical trial.Before enrollment, patients( 3 2) cur rently receiving ocular hypotensive medication underwent a wash-out period (four weeks for beta-blockers; three weeks with epinephrine pro ducts; 48 hours for pilocarpine.Af ter wash-out, baseline intra-ocular pressure measurements were taken before 11:00 a.m. on two separate days, not less than three days apart.Enrollment was permitted if each of these two measurements was greater than 23 mmHg at least one eye.Addtional exclusion criteria for participation in the study included: recent history of ocular, trauma, in fe ction or inflamatory diseases, any abnonnality preventing reliable ap planation tonometry, history of reti nal detachment, diabetic retinopathy, or any retinal disease that could be expected to be progressive, intrao cular surgery in the last six months, current contact lens wear, any unsta ble cardiovascular or pulmonary di sease, current use of systemic beta blocker hypersensitivity to betaxolol or to any formulation component, pregnant or nursing women and of ± 0.4 Least Significant Differences (LSD) x = P < 0.05 xx = P < 0. 01 xxx = P < 0. 00 1 Comparing with the average of obtained pressures in the pre-therapy phase with the ones obtained in the examinations during the whole study, we have: = 8.3 mmHg (33.0%)Pulse: We obtained the fo llowing fi gures with the 20 patients studied : = 8. 3mmHg (33.0%)Arterial Tension: The average of arterial tension in pre-therapy phase compared with the average of the ones observed during treatment has shown the following figures: Pre-Therapy Average during treatment Maximum = 128 mmHg 124 mmHg = 4 mmHg Minimum = 80 mmHg 78 mmHg = 2 mmHg Visual Acuity: Visual acuity was unaltered in 18 (90%) patients, ha ving improved in 2 (10%) patients (4 eyes) -the nrs.7 and 8 of the study.Pallent nr.7 Pre-therapy .12th week R.E.= 20/60 improved to 20/40 L.E. = 20/400 improved to 20/1 00 This is the sarne patient who a1so showed improvement in visual fiel ds.Pallent nr. 8 Pre-therapy 12th week R.E.= 20/40 mproved to L. E. = 20/40 improved to 20/30 20/30

Fundos
Exam;nations: Retina and optical nerve ' have DOt shown altera tions along the treatment.LocaI Symptoms: It was searched for in alI patients by using the fo llo wing scale:

IntraocularArterial
Pressure:IOP average in mmHg on the 38 eyes, measured on pretherapy phase and on the fo l lowing examinations are shown be low: signlficant differences (LSO) x = P < 0.05 xx = P < 0.01 xxx = P < 0.001 Comparing IOP average measured on pre-therapy phase with the avera ge of the pressUDe measures along the treatment during the 12 weeks of the study, we have the following fi gures: Pre-Therapy Fol lowlng Examinations 26.2 15.9 = 10.3 (39.3%)PbIse: The fo llowing figures were obtained from 20 patients during the study.Tensioo: The figures be low were obtained from the average of pretherapy arterial tension compa red with the average of the arterial tensions along the treatment.Pre-therapy Average during treatment Maximum = 135 mmHg 126 mmHg = 9 mmHg Mlnimum = 83 mmHg 78 mmHg = 5 mmHg Visual Acuity: Unchanged during the treatment .

Systemic a1terations :
We have ob served significant differences in Pul se and Arterial Tension (LSD Te st).LocaI SymptOlllS : Oot of 20 pa tients, 5 did not present complaints (O) , 15 presented weak burning whi ch have disappeared in 6 of them up to the end of the treatment.

12 xolol
should be considered the drug of choice for patients who need ocular hypotensive medication and who suffer from c}lfonic obstructi ve pulmonary disease, chronic asthma and chronic bronchitis.ACKNOWLEDGEMENT Edgar Mario Wagner Statistics Professor Faculdade de Medicina da Universidade Federal do Rio Grande do Sul SUMMAR Y This artiele shows a double mas ked study between Betaxolol 0.5% drops and Levobwwlol 0.5% drops involving 40 glaucomatous patients .20 randomized patients were gi ven Betaxolol.And other 20 patients were given Levobunolol in a rando mized way as well.This work developed over a pe riod of 12 weeks during whieh time the effeets of the above mentioned drugs on the ocular were observed sp eeially over the Intraocular Pres sure as well as their possible syste mie effeets .BIBUOGRAPHY I. Berrospi, A.R., Leibowitz, H. W.: Betaxo-101: A new -adrenergie blocldng agent for the treatment of glaucoma.Arch.Oph �. 1982, 100: 943-946.

TABLE 1
• • P <0.001 II trennenI means tItIII r.nt 110m blseIM VlUS p>O.oS no dtllem1ct bll twMn treatnenl me.ns A double-masked comparison of betaxo/ol and levobuno/ol for the treatment of primary open-angle glaucoma Heart Rate: A significant reduction in the mean heart rate values was measured at weeks 1, 4, 8 and 12 ARQ.BRAS.OFr AL. 53(1), 1990