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hyperoxia with a vasoconstrictive response and reduced 3. Hutzelmann J, Owens S, Shedden A, Adamsons I, Vargas E.
blood flow. The superior retina alone responded to hyper- Comparison of the safety and efficacy of the fixed combina-
capnea with a vasodilatory response, and increased blood tion of dorzolamide/timolol and the concomitant adminis-
tration of dorzolamide and timolol: a clinical equivalence
flow. In the current study, a vasodilatory stimulus was study. International Clinical Equivalence Study Group. Br J
applied to the eye, but the superior retina alone reacted Ophthalmol 1998;82:1249–1253.
with a vasodilatory response. This isolated response is 4. Hayreh SS. The Von Sallman Lecture. The optic nerve head
consistent with previously published data. circulation in health and disease. Exp Eye Res 1995;1994:
As further evidence for a lack of vascular effect in the 61:259–272.
perimacular choroid, we also found that indocyanine green 5. Harris A, Arend O, Kagemann L, Garrett M, Chung HS,
Martin B. Dorzolamide, visual function and ocular hemody-
angiograms, which qualitatively assess choroid perfusion in namics in normal-tension glaucoma. J Ocul Pharmacol Ther
the peripapillary and perimacular regions, were unaltered 1999;15:189–197.
by the dorzolamide-timolol combination. Indocyanine 6. Harris A, Kagemann L, Chung HS, Ciulla TA. The use of
green response times, rate of dye intensity increase, and dye dilution curve analysis in the quantification of indocya-
dye duration were unaltered, either in the aggregate of the nine green angiograms of the human choroid. Ophthalmol
Clin North Am 1998;11:331–337.
six peripapillary and perimacular regions, or in any indi- 7. Stewart WC, Garrison PM. Beta-blocker-induced complica-
vidual region, by dorzolamide addition. This finding sug- tions and the patient with glaucoma. Newer treatments to
gests that dorzolamide leaves choroidal flow to these help reduce systemic adverse events. Arch Intern Med
regions unchanged. Although some past work has shown 1998;158:221–226.
6
that the ocular pulse amplitude, a rough index of the bulk 8. Harris A, Arend O, Arend S, Martin B. Effects of topical
dorzolamide on retinal and retrobulbar hemodynamics. Acta
choroidal perfusion, is enhanced by dorzolamide in glau- Ophthalmol Scand 1996;74:569–572.
coma, our results suggest that addition of dorzolamide to 9. Grunwald JE, Zinn H. The acute effect of oral acetazolamide
21
timolol does not alter juxtapapillary or perimacular cho- on macular blood flow. Invest Ophthalmol Vis Sci 1992;33:
roidal perfusion in these patients. 504–507.
Topical carbonic anhydrase inhibitors, although clearly 10. Grunwald JE, Mathur S, DuPont J. Effects of dorzolamide
hydrochloride 2% on the retinal circulation. Acta Ophthal-
penetrating to the ciliary processes by means of both mol Scand 1997;75:236–238.
corneal and extracorneal routes, 1,15 have not been shown 11. Grunwald JE, Riva CE, Stone RA, Keates EU, Petrig BL.
to reach deeper ocular structures, and in healthy subjects Retinal autoregulation in open-angle glaucoma. Ophthal-
or in patients with normal-tension glaucoma have no mology 1984;91:1690–1694.
effect on flow velocities in retrobulbar arteries. 5,8 In this 12. Harris A, Arend O, Chung HS, Kagemann L, Cantor L,
Martin B. A comparative study of betaxolol and dorzolamide
study, in patients with glaucoma receiving baseline treat- on the ocular circulation in normal-tension glaucoma pa-
ment with timolol, addition of dorzolamide again had no tients. Ophthalmology 2000;107: 430–434.
measurable hemodynamic effect in the retrobulbar vascula- 13. Ehrenreich DL, Burns RA, Alman RW, Razekas JF. Influence
ture. Our findings imply either that penetration of drug to the of acetazolamide on cerebral blood flow. Arch Neurol 1961;
back of the eye is limited, or that its impact on flow within, 5:125–130.
and vascular resistance distal to, each of these vessels is 14. Rassam SM, Patel V, Kohner EM. The effect of acetazol-
amide on the retinal circulation. Eye 1993;7:697–702.
unimportant. 1,15 Our findings underscore the limited hemo- 15. Schmitz K, Banditt P, Motschmann M, Meyer FP, Behrens-
dynamic impact of topical dorzolamide behind the globe. Baumann W. Population pharmacokinetics of 2% topical
In summary, dorzolamide augmentation of timolol fur- dorzolamide in the aqueous humor of humans. Invest Oph-
ther lowers intraocular pressure in primary open-angle thalmol Vis Sci 1999;40:1621–1624.
glaucoma and increases indexes of retinal perfusion. 16. Wang Q, Bryowsky J, Minshall RD, Pelligrino DA. Possible
obligatory functions of cyclic nucleotides in hypercapnia-
Whether the hemodynamic alterations are a direct action induced cerebral vasodilation in adult rats. Am J Physiol
of local carbonic anhydrase inhibitor or secondary to 1999;276:H480–H487.
reduced intraocular pressure remains unknown. 17. Sponsel WE, Harrison J, Elliott WR, Trigo Y, Kavanagh J,
Harris A. Dorzolamide hydrochloride and visual function in
normal eyes. Am J Ophthalmol 1997;123:759–766.
18. Janssen P, Naskar R, Moore S, Thanos S, Thiel HJ. Evidence
REFERENCES for glaucoma-induced horizontal cell alterations in the hu-
man retina. Ger J Ophthalmol 1996;5:378–385.
1. Maren TH, Conroy CW, Wynns GC, Levy NS. Ocular 19. Kendell KR, Quigley HA, Kerrigan LA, Pease ME, Quigley
absorption, blood levels, and excretion of dorzolamide, a EN. Primary open-angle glaucoma is not associated with pho-
topically active carbonic anhydrase inhibitor. J Ocul Phar- toreceptor loss. Invest Ophthalmol Vis Sci 1995;36:200–205.
macol Ther 1997;13:23–30. 20. Chung HS, Harris A, Halter PJ, et al. Regional differences in
2. Clineschmidt CM, Williams RD, Snyder E, Adamsons IA. A retinal vascular reactivity. Invest Ophthalmol Vis Sci 1999;
randomized trial in patients inadequately controlled with 40:2448–2453.
timolol alone comparing the dorzolamide-timolol combina- 21. Schmidt KG, von Ruckmann A, Pillunat LE. Topical car-
tion to monotherapy with timolol or dorzolamide. Dorzol- bonic anhydrase inhibition increases ocular pulse amplitude
amide-Timolol Combination Study Group. Ophthalmology in high tension primary open angle glaucoma. Br J Ophthal-
1998;105:1952–1959. mol 1998;82:758–762.
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