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`Santen/Asahi Glass Exhibit 2011
`Micro Labs v. Santen Pharm. and Asahi Glass
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`Fig. 1. Mean change in IOP of 18 patients versus time.
`PGF2M (200 pg) 7 treated eyes: points; placebo—treated
`eyes: circles; i1 SD: bars
`
`«
`.
`Flg. 2. IOP difference between the PG—treated and
`the placebo-treated eye in each of 18 patients
`versus time. Points represent the IOP differences in
`each patient
`
`Fig. 3. Mean change in pupillary
`diameter of 18 patients versus time.
`PGFZa (200 pg) 7 treated eyes:
`points; placebo-treated eyes: circles;
`-_l-1 SD: bars
`
`140
`
`E)I
`
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`(L
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`: 3
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`
`H Prostaglandin F20
`O--O Placebo
`
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`alter
`treatment
`
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`
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`
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`
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`
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`
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`
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`24
`
`Discussion
`
`This study indicates that topical PGs can reduce IOP in
`humans. In nonglaucomatous subjects 200 ug of PGFZa re-
`duces IOP up to about 30% of pretreatment values and
`produces some hypotension for 24 h at least.
`Zajacs et a1. (1976) has found an IOP reduction in preg-
`
`nant women after intravenous or intrauterine administra—
`tion of PGs to induce abortions. Although ocular hyperten-
`sion induced by exogenous PG in humans has not been
`reported before now a similar effect has been shown in
`experimental animals. In the rabbit, Camras et a1. (1977)
`have observed that topical PGFZM and PGE2 produce an
`immediate rise in the IOP, followed by a reduction that
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`141
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`lasts many hours. The initial hypertensive response did not
`occur with the use of 5 pg or less of PGFZa. A similar
`biphasic response has been shown by Stern and Bito (1982)
`in the cat and in the rhesus monkey. The higher doses of
`PGFZu produced an initial rise in IOP before the hypotony,
`without aqueous flare. Miosis occurred in the cat eye but
`not in the monkey eye. In our patients no change in the
`pupillary diameter or the blood-aqueous barrier permeabili-
`ty was evoked by PGFZQ, Which is similar to the results
`obtained by Stern and Bite (1982) in the rhesus monkey.
`The ocular hypotensive effect of the PGs may be due to
`an increase in the aqueous—humor outflow facility, which
`Green and Kim (1975) and Moses et al. (1981) have demon-
`strated in the rabbit eye.
`Since PGs reduce IOP and do not change the pupillary
`diameter and blood—aqueous barrier, they could represent
`a new pharmacological approach to the therapy of ocular
`hypertensions. However, a serious handicap in their use
`is the unfavorable side effects of ocular pain, conjunctival
`hyperemia and headache, which could discourage their use
`in Chronic therapy.
`
`Camras CB, Bito LZ (1981) Reduction of intraocular pressure in
`normal and glaucomatous primate (Aotus trivirgatus) eyes by
`topically applied prostaglandin F21. Curr Eye Res 12205—209
`Camras CB, Bito LZ, Eakins KE (1977) Reduction of intraocular
`pressure by prostaglandins applied topically t0 the eyes of con-
`scious rabbits. Invest Ophthalmol Vis Sci 16: 1125‘1134
`Eakins KE (1977) Prostaglandin and non-prostaglandin mediated
`breakdown of the blood aqueous barrier. Exp Eye Res [Suppl]
`25:483~498
`Green K, Kim K (1975) Pattern of ocular response to topical and
`systemic prostaglandin. Invest Ophthalmol 14: 36-40
`Moses RA, Parkison G, Snower DP (1981) Prostaglandin E2 effect
`on the facility of outflow in the rabbit eye. Ann Ophthalmol
`1327217723
`Starr MS (1971) Further studies on the effect of prostaglandin
`on intraocular pressure in the rabbit. Exp Eye Res 11 :1707177
`Stern FA, Bito LZ (1982) Comparison of the hypotensive and
`other ocular effects of prostaglandins E2 and F21 on cat and
`rhesus monkey eyes. Invest Ophthalmol Vis Sci 22: 5887598
`Waitzman MB, King CD (1967) Prostaglandin influences on in»
`traocular pressure and pupil size. Am J Physiol 212: 3297334
`Zajacs M, Torok M, Mocscry P (1976) Effect on human eye of
`prostaglandin and a prostaglandin analogue used to induce
`abortion. IRCS Med Sci 4:31fl321
`
`References
`
`Beitch BR, Eakins KE (1969) The effects of prostaglandins on
`the intraocular pressure of
`the rabbit. Br
`J Pharmacol
`37:158—167
`
`Received July 30, 1984
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