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Mehmet Okka, MD; Baohe Tian, MD; Paul L. Kaufman, MD

Arch Ophthalmol. 2004;122:1482-1488.

Objectives  To determine if low doses of topical latrunculin B (LAT-B) will increase outflow facility and decrease intraocular pressure without damaging the cornea and if they will inhibit miotic and accommodative responses to pilocarpine in monkeys.

Methods  We measured intraocular pressure (Goldmann tonometry) before and after 1 and 9 doses of 0.005% and 0.01% topical LAT-B and vehicle given twice daily on successive weeks; outflow facility (perfusion) following 15 doses; central corneal thickness (ultrasonic pachymetry) before and after 1 and 9 doses of 0.01% LAT-B and vehicle; pupillary diameter (calipers); and accommodation (refractometry) before and after 1 dose of 0.005% and 0.02% LAT-B.

Results  Latrunculin-B dose-dependently decreased intraocular pressure, multiple doses more than a single dose. Maximal mean ± SEM hypotension after 1 dose was 2.5 ± 0.3 mm Hg (0.005% LAT-B; n = 8; P<.001) or 2.7 ± 0.6 mm Hg (0.01% LAT-B; n = 8; P<.005); maximal mean ± SEM hypotension after 9 doses was 3.2 ± 0.5 mm Hg (0.005% LAT-B; n = 8; P<.001) or 4.4 ± 0.6 mm Hg (0.01% LAT-B; n = 8; P<.001). Outflow facility was increased by mean ± SEM 75% ± 13% (n = 7; P<.005). Central corneal thickness was not changed after 1 or 9 doses of 0.01% LAT-B. Miotic and accommodative responses to intramuscular pilocarpine were dose-dependently inhibited. With 0.02% LAT-B, inhibition of miosis was substantial, whereas the inhibition of accommodation was only about 25%. With 0.005% LAT-B, the effects were trivial.

Conclusions  In ocular normotensive monkeys, 0.005% and 0.01% LAT-B administered topically increases outflow facility and/or decreases intraocular pressure without corneal effects. Multiple doses reduce intraocular pressure more than a single dose. Latrunculin-B dose-dependently relaxes the iris sphincter and ciliary muscle, with some separation of miotic and accommodative effects.

Clinical Relevance  Multiple treatments with low topical doses of LAT-B may substantially reduce outflow resistance in eyes with glaucoma without adversely affecting the cornea.

From the Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison Medical School, Madison. The University of Wisconsin Wisconsin Alumni Research Foundation, Madison, holds a patent related to latrunculin B; accordingly, Dr Kaufman has a proprietary interest.

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