Glaucoma was induced in cynomolgus monkeys by photocoagulating the trabecular meshwork with the argon laser. Repeat treatments were often necessary and wide intraocular pressure fluctuations were ...characteristic. Baseline intraocular pressure was measured with a calibrated pneumatonometer hourly for six hours. On a succeeding day a baseline measurement was made, 50 microliter of the drug to be tested applied, and six hourly measurements of intraocular pressure repeated. The effects on intraocular pressure of timolol, epinephrine, pilocarpine, vanadate, prostaglandin F2 alpha (PGF2 alpha), forskolin, and corynanthine were tested in at least eight eyes. Significant (p less than 0.05) reductions of intraocular pressure were produced by 0.5% timolol, 2% epinephrine, 4% pilocarpine, 1% vanadate, 500 micrograms of PGF2 alpha and 1% forskolin. Five per cent corynanthine produced no significant lowering of intraocular pressure. Tonography revealed an increased outflow facility associated with the reduction of intraocular pressure 2 hours after the administration of 4% pilocarpine. This glaucoma animal model may be useful in investigating agents that lower intraocular pressure by a variety of mechanisms.
To compare the ocular hypotensive effect of the commercially available preparations of bimatoprost or travoprost added to latanoprost in monkey eyes with laser-induced unilateral glaucoma.
Four ...monkeys with unilateral laser-induced glaucoma were used in each treatment group and received drops in the glaucomatous eye only. Intraocular pressure (IOP) was measured hourly for 6 hours, beginning at 9:30 am on day 1 (untreated baseline), days 6 and 7 (single-agent therapy), and days 13 and 14 (2-drug combination therapy). On days 2 through 7, 1 drop of the scheduled single agent was given immediately after the 9:30 am IOP measurement, and on days 8 through 14, the second scheduled drug was given 5 minutes after the first. The following 5 different dosing protocols were studied: latanoprost with bimatoprost added, bimatoprost with latanoprost added, latanoprost with travoprost added, travoprost with latanoprost added, and latanoprost with a second dose of latanoprost added.
There were no statistically significant (P =.95) differences among the mean baseline IOPs in any of the 5 treatment groups. When applied as single agents, latanoprost, bimatoprost, and travoprost all produced significant (P<.05) and equivalent (P =.98) reductions in IOP. The mean +/-SEM maximum reduction (P<.05) from baseline IOP was 7.0 +/- 0.4 mm Hg (20% reduction) with travoprost alone, 6.5 +/- 1.6 mm Hg (18%) with bimatoprost alone, and 7.5 +/- 1.0 mm Hg (22%) with latanoprost alone. The mean +/-SEM maximum additive reductions in IOP were 3.0 +/- 0.6 mm Hg (P<.05) for travoprost added to latanoprost; 2.0 +/- 0.4 mm Hg (P<.05) for latanoprost added to travoprost; 4.8 +/- 1.3 mm Hg (P<.05) for bimatoprost added to latanoprost; 4.3 +/- 0.6 mm Hg (P<.05) for latanoprost added to bimatoprost; and 0.3 +/- 0.5 mm Hg (P>.60) for latanoprost added to itself. The combination of bimatoprost and latanoprost produced a greater (P<.05) lowering of IOP at trough and peak than the combination of travoprost and latanoprost.
Latanoprost, bimatoprost, and travoprost used as monotherapy produced significant and equivalent reductions in IOP in glaucomatous monkey eyes. The IOP effects of the commercial concentrations of bimatoprost or travoprost were additive to that of latanoprost, with bimatoprost showing a greater additive response than travoprost. Clinical Relevance Because treatment with multiple medications is common among patients with glaucoma, determining which glaucoma medications produce an additive ocular hypotensive response when used in combination has practical implications for clinicians.
Ocular hypertensive patients were enrolled in a 6-week double-masked safety study of 2% MK-927 (27 patients), a topically active carbonic anhydrase inhibitor, administered bilaterally b.i.d.; 9 ...additional patients received 0.5% timolol as the control agent. Intraocular pressure (IOP) was measured weekly prior to a.m. drug administration; twelve hour diurnal curves were performed prestudy and at 3 and 6 weeks. The mean reduction of IOP prior to a.m. drug administration ranged from 1.2 +/- 4.4 mm Hg (SD) to 3.0 +/- 4.2 mm Hg with MK-927 and from 4.7 +/- 3.9 mm Hg to 8.8 +/- 0.6 mm Hg with timolol. Mean outflow facility measured tonographically prestudy and on days 33 to 42 four hours after a.m. drug administration was unchanged in both groups. Corneal sensitivity (Cochet-Bonnet), corneal thickness (ultrasound pachymetry), Schirmer tear testing, and extensive ophthalmologic and medical examinations, and hematologic studies were not substantially altered throughout the study. In this longest chronic administration study to date, MK-927 did not cause adverse ocular or systemic side effects.
By using a continuous wave argon laser in a multiburn fashion, successful iridectomies were achieved in 42 out of 45 phakic eyes with either acute or chronic angle-closure glaucoma. Five of the ...successful procedures required multiple sittings on different days or abandonment of the primary treatment site in favor of an alternate site, or both, to attain patency. Within the immediate postoperative period, ten eyes needed retreatment to eliminate moderate pigment proliferation at the perforation site. The procedure was performed on an outpatient basis under topical anesthesia, usually required less than one-half hour for completion, and resulted in only minimal complications. Therefore, continuous wave argon laser iridectomy appears to present a viable alternative to surgical iridectomy for the definitive treatment of angle-closure glaucoma, although long-term evaluation of this modality of therapy is presently unavailable.
Four black patients, all with sickle trait (SA), developed transient open-angle glaucoma with blood in Schlemm's canal. In 3 patients the condition followed blunt trauma, while in the fourth no ...antecedent trauma was described. The intraocular pressure became normal in all 4 cases with the resolution of the haemorrhage from the trabecular meshwork and Schlemm's canal.
Forty-five phakic eyes with open-angle glaucoma and uncontrolled intraocular pressure underwent laser trabeculoplasty. Each eye was assigned randomly to one of three treatment groups: group 1, 100 ...spots over 360 degrees; group 2, 50 spots over 180 degrees; or group 3, 50 spots over 360 degrees. A 50-micron spot was aimed at the anterior meshwork; power and time were varied to achieve a blanch. Forty-four eyes were followed up for at least four weeks without further intervention. The mean IOP before therapy and the initial IOP elevation were similar in all groups. After four weeks, the mean IOP reductions in 15 eyes in group 1, 15 eyes in group 2, and 14 eyes in group 3 were not significantly different. However, significantly more eyes in group 1 demonstrated a greater than 12 mm Hg reduction in IOP than eyes in the other groups. Group 2 tended to have the fewest eyes with reduced medications.
We investigated the dose-response and reproducibility of the intraocular pressure-lowering effect of MK-927 in ocular hypertensive patients. Patients were enrolled until at least 8 "marked ...responders" (peak reduction in intraocular pressure comparing the MK-927-treated eye with the placebo-treated eye greater than or equal to 6 mm Hg) and 7 "mild responders" (peak reduction in intraocular pressure comparing the MK-927-treated eye with the placebo-treated eye less than or equal to 3 mm Hg) were identified. In part A, 27 patients received one drop of 2% MK-927 in one eye (baseline mean +/- SEM intraocular pressure, 28.0 +/- 1.0 mm Hg) and placebo in the contralateral eye. Intraocular pressure was measured at baseline and 1, 2, 3, 4, and 6 hours. Maximum reduction in intraocular pressure was 4.0 +/- 0.8 mm Hg at 3 hours, with a duration of 4 hours. Ten patients were identified as marked responders and 7 as mild responders. In part B, 8 of the marked responders entered a four-period crossover study and received 2%, 0.5%, and 0.125% MK-927 and placebo in the same treated eye as in part A, and placebo in the contralateral eye. The 7 mild responders in part C received 2% MK-927 in a similar fashion as in part A. MK-927 in concentrations of 0.125% and 0.5% had little or no effect on intraocular pressure in patients with a marked response to 2% MK-927. Within-patient variability in peak response to single doses of 2% MK-927 was substantial (coefficient of variation of 0.3 and 0.5 for marked responder and mild responder groups, respectively.
PDF
