Reduktion der okulären Pulsamplitude unter Apraclonidin - prospektive doppelt maskierte Studie an 10 Probanden

Gabriele B. Kuba; Patricia Austermann

doi:10.1055/s-2001-13079

Klinische Monatsblätter für Augenheilkunde, Table of Contents

Klin Monbl Augenheilkd 2001; 218(3): 187-191
DOI: 10.1055/s-2001-13079

KLINISCHE STUDIE

Georg Thieme Verlag Stuttgart · New York

Reduktion der okulären Pulsamplitude unter Apraclonidin - prospektive doppelt maskierte Studie an 10 Probanden[1]

Reduction of ocular pulse amplitude as effect of Apraclonidin - prospective double masked, randomized clinical trial in 10 subjectsGabriele B. Kuba, Patricia Austermann

Medizinisches Zentrum für Augenheilkunde der Philipps-Universität Marburg, Robert-Koch-Str. 4, 35037 Marburg
(geschäftsführender Direktor: Prof. Dr. P. Kroll)

Abstract

Zusammenfassung

Hintergrund Die effektive augeninnendrucksenkende Wirkung des α-Agonisten Apraclonidin ist hinreichend bekannt. Da jedoch Perfusionsstörungen in der Pathogenese der primären Offenwinkelglaukome zunehmend an Bedeutung gewinnen, sollte ein antiglaukomatöses Medikament auch hinsichtlich seiner Auswirkung auf die okuläre Zirkulation beurteilt werden.

Methode In einer prospektiven doppelt maskierten Studie applizierten 10 Probanden 0,5 % Apraclonidin-AT, und 10 Probanden Plazebo-AT (0,9 % NaCl), 2 × täglich für 8 Tage. IOD, Puls, Blutdruck und okuläre Pulsamplituden (OBF Labs, UK) wurden initial (1T0), 90 min nach Tropfapplikation (1T90), nach 7-tägiger Therapie (8T0) und nach erneuter Tropfapplikation (8T90) gemessen. Die statistische Auswertung erfolgte mit dem Wilcoxon-Test für verbundene Stichproben.

Ergebnisse In der Apraclonidin-Gruppe sank der IOD signifikant (p < 0,01) von 15,6 mm Hg auf 11,4/12,4/10,3 mm Hg (1T0/1T90/8T0/8T90). In der Kontrollgruppe zeigte sich ein Abfall zu 8T0 (p = 0,02). Der Blutdruck blieb in beiden Gruppen konstant, der Puls zeigte in der Kontrollgruppe zu 1T90 einen Abfall. Die Pulsamplitude fiel in der Apraclonidin-Gruppe zu 1T90 (p = 0,01) und zu 8T90 (p = 0,005) signifikant von 3,22 mm Hg auf 2,48/3,1/2,35 mm Hg (1T0/1T90/8T0/8T90) und blieb in der Kontrollgruppe unverändert.

Schlussfolgerung Während einer 1-wöchigen Therapie mit 0,5 % Apraclonidin kam es erwartungsgemäß zu einem signifikanten Abfall des Augeninnendruckes bei gesunden Probanden. Die beobachtete Reduktion der okulären Pulsamplituden könnte sich jedoch in der Langzeittherapie bei Patienten mit chronischem Offenwinkelglaukom ungünstig auswirken.

Background The α-agonist Apraclonidin lowers effective intraocular pressure. Ischemia gains increasing importance in the pathogenesis of glaucoma. Therefore, an antiglaucomatous drug should also be investigated in regard of its influence on ocular hemodynamics.

Methods In a double masked, randomized, clinical trial 0.5 % Apraclonidin eye drops were applied in 10 healthy subjects twice daily for 8 days. The control group (10 healthy volunteers) received a placebo medication (0.9 % NaCl) according to the same protocol. IOP, heart rate, blood pressure and ocular pulse amplitudes (OBF Labs, UK) were measured at baseline (1T0), 90 minutes after instillation of one eye drop (1T90), after 7 days of therapy (8T0) and again 90 minutes after an acute instillation (8T90). For statistical analysis the wilcoxon test for paired samples was used.

Results In Apraclonidin treated subjects IOP dropped significantly (p < 0.01) from 15.6 mm Hg to 11.4/12.4/10.3 mm Hg (1T0/1T90/8T0/8T90). The control group showed a significant drop at 8T0 (p = 0.02). The blood pressure remained constant in both groups, the heart rate showed a drop in the control group at 1T90. In Apraclonidin treated subjects the pulse amplitude showed a significant reduction at 1T90 (p = 0.01) and at 8T90 (p = 0.005) from 3.22 mm Hg to 2.48/3.1/2.35 mm Hg (1T0/1T90/8T0/8T90), in the control group the pulse amplitude remained constant.

Conclusion After one week of therapy with 0.5 % Apraclonidin, intraocular pressure dropped as expected in healthy volunteers. The observed reduction in pulse amplitudes however could have a negative effect on long-term therapy in patients with chronic open-angle glaucoma.

Schlüsselwörter

Apraclonidin - chronisches Offenwinkelglaukom - Glaukomtherapie - okuläre Hämodynamik - okuläre Pulsamplitude

Key words

Apraclonidin - chronic open-angle glaucoma - glaucoma therapy - ocluar hemodynamics - ocular pulse amplitude

Full Text

References

Literatur

01 ¹ Manuskript erstmalig eingereicht am 9. 6. 00 und in der vorliegenden Form angenommen am 11. 8. 00.

01 Gharagozloo N Z, Relf S J, Brubaker R F. Aqueous flow is reduced in the alpha-adrenergic agonist, apraclonidine hydrochloride. Ophthalmology. 1988; 95 1217-1220.
02 Lee D A, Topper J E, Brubaker R F. Effect of clonidine on aqueous humor flow in normal human eyes. Exp Eye Res. 1984; 38 239-246.
03 Robin A L. Short-term effects of unilateral 1 % apraclonidine therapy. Arch Ophthalmol. 1988; 106 912-915.
04 Robin A L. Questions Concerning the Role of Apraclonidine in the Management of Glaucoma. Arch Ophthalmol. 1995; 113 712-714.
05 Kim T W, Kim D M. Effects of 0,5 % apraclonidine on optic nerve head and peripapillary retinal blood flow. Br J Ophthalmol. 1997; 81 1070-1072.
06 Brown R H, Stewart R H, Lynch M G et al. ALO 2145 reduces the intraocular pressure elevation after anterior segment laser surgery. Ophthalmology. 1988; 95 378-384.
07 Kitazawa Y, Taniguchi T, Sugiyama K. Use of apraclonidine to reduce acute intraocular pressure rise following Q-Switched Nd:YAG laser iridotomy. Ophthalmic Surg. 1989; 20 49-52.
08 Abrams D A, Robin A L, Crandall A, Caldwell D, Schnitzer D, Pollak I. A limited comparison of apraclonidine's dose response in subjects with normal or increased intraocular pressure. Am J Ophthalmol. 1989; 108 230-237.
09 Abrams D A, Robin A L, Pollak I P, De Faller J M, De Santis L. The safety and efficiacy of topical 1 % ALO 2145 in normal volunteers. Arch Ophthalmol. 1987; 105 1205-1207.
10 Jampel H, Robin A L, Quigley H, Pollack I P. Apraclonidine hydrochloride: a 1-week dose-response study. Arch Ophthalmol. 1988; 106 1069-1073.
11 Pollack I P, Brown R, Crandall A, Robin A L, Stewart R, White G. Prevention of the rise in intraocular pressure following neodymium-YAG posterior capsulotomy using topical 1 % apraclonidine. Arch Ophthalmol. 1988; 106 754-757.
12 Silverstone D, Brint S, Olander K, Taylor R, McCarty G, De Faller J. Prophylactic use of apraclonidine for intraocular pressure increase after Nd:YAG capsulotomies. Am J Ophthalmol. 1992; 113 491-495.
13 Stewart W C, Ritch R, Shin D H, Lehmann R P, Shrader E, van Buskirk M. The efficiacy of apraclonidine as an adjunct to timolol therapy. Arch Ophthalmol. 1995; 113 287-292.
14 Cardakli J, Smythe B, Eisele J, Kaufman P, Perkins T. Effect of chronic apraclonidine treatment on intraocular pressure in advance glaucoma. J Glaucoma. 1994; 2 271-278.
15 Lish A, Camras C, Podos S. Effect of apraclonidine on intraocular pressure in glaucoma patients receiving maximally tolerated medications. J Glaucoma. 1992; 1 19-22.
16 Pape L, Ritch R, Paqua J, Steinberger D. Long-term compassionate use of apraclonidine 0,25 % for refractory glaucoma. Invest Ophthalmol Vis Sci. 1992; 33 (Suppl) page 1247.
17 Drance S M. Glaucoma: a look geyond intraocular pressure. Am J Ophthalmol. 1997; 123 817-819.
18 Pillunat L E, Anderson D R, Knighton R W, Joos K M, Feuer W J. Autoregulation of human optic nerve head circulation in response to increased intraocular pressure. Exp Eye Res. 1997; 64 737-744.
19 Pillunat L E, Stodtmeister R, Wilmanns I. Pressure compliance of the optic nerve head in low tension glaucoma. Br J Ophthalmol. 1987; 71 181-187.
20 Coleman A L, Robin A L, Pollack I P. Cardiovascular and Intraocular Pressure Effects and Plasma Concentrations of Apraclonidine. Arch Ophthalmol. 1990; 108 1264-1267.
21 Robin A L, Pollack I P, De Faller J M. Effects of topical ALO 2145 on the acute intraocular pressure rise after argon laser iridotomy. Arch Ophthalmol. 1987; 105 1208-1211.
22 Robin A L, Pollack I P, House B, Enger C. Effects of ALO 2145 on intraocular pressure following argon laser trabeculoplasty. Arch Ophthalmol. 1987; 105 646-650.
23 Eisenlohr J E, Langham M E, Maumenee A E. Manometric studies of pressure-volume-relationship in living and enucleated eyes of individual human subjects. Br J Ophthalmol. 1962; 46 536-548.
24 Langham M E, Farrell R A, O'Brien V, Silver D M, Schilder P. Blood Flow in the Human Eye. Acta Ophthalmologica. 1989; 67 9-13.
25 Silver D M, Farrell R A, O'Brien V, Schilder P. Estimation of Pulsatile Ocular Blood Flow from Intraocular Pressure. Acta Ophthalmologica. 1989; 67 25-29.
26 Robinson F, Chen S, Petrig B L, Grunwald J E, Riva C E. The acute effect of topical epinephrine on macular blood flow in humans. Invest Ophthalmol Vis Sci. 1992; 33 18-22.
27 Robinson F, Petrig B L, Sinclair S H, Riva C E, Grunwald J E. Does topical phenylephrine, tropicamid or proparacaine affect macular blood flow?. Ophthalmology. 1985; 92 1130-1132.
28 Schmetterer L, Strenn K, Findl O, Breieneder H, Gaselli U, Agneter E, Eichler H G, Woltz M. Effects of antiglaucoma drugs on ocular hemodynamics in healthy volunteers. Clin Pharmacol Ther. 1997; 61 583-595.
29 Groh M JM, Michelson G, Harazny J, Groh M, Koschinsky K. Retinale Blutflussveränderungen durch topische Gabe von Dipivefrin 0,1 %. Ophthalmologe. 1999; 96 706-710.
30 Kanzow U, Pillunat L E, Böhm A G et al. Scanning Laser Doppler Flowmetry after topical brimonidine administration. Invest Ophthalmol Vis Sci. 1998; Suppl 39 page 271.
31 Carlsson A M, Cauhan B C, Lee A, Le Blanc R P. Effects of 0,2 % brimonidine tartrate on retinal blood flow in ocular hypertension. Can J Ophthalmol. 1998; 33 102-103.
32 Lachkar Y, Migdal C, Dhanjil S. Effect of brimonidine tartrate on ocular hemodynamic measurements. Arch Ophthalmol. 1998; 116 1591-1594.
33 Harris A, Caldemeyer K S, Mansberger S L, Martin B J. α-Adrenergic agonists' effects on oculr hemodynamics. J Glaucoma. 1995; 4 (Suppl. 1) 19-23.
34 Celiker Ü Ö, Celebi S, Celiker H, Celebi H. Effect of topical apraclonidine on flow properties of central retinal and ophthalmic arteries. Acta Ophthalmol. 1996; 74 151-154.
35 Cioffi G A, Orgül S, Bacon D R, Van Buskirk E M. Acute vasomotor effects in the anterior optic nerve of topical apraclonidine hydrochloride. J Glaucoma. 1995; 4 (Suppl. 1) 15-18.
36 Orgül S, Bacon D R, Van Buskirk E M, Cioffi G A. Optic nerve vasomotor effects of topical apraclonidine hydrochloride. Br J Ophthalmol. 1996; 80 82-84