D.J. Gagliuso

Comparison of the ocular hypotensive effect of brimonidine, dorzolamide, latanoprost, or artificial tears added to timolol in glaucomatous monkey eyes.

Purpose: To investigate the additive ocular hypotensive effect of brimonidine, dorzolamide, latanoprost, or artificial tears to timolol in monkey eyes with laserinduced unilateral glaucoma. Methods: Eight monkeys were used and each animal received all four combinations of drugs in a randomized fashion during the study. The washout period between each combination was at least 2 weeks. Intraocular pressure (IOP) was measured at 8:30 AM, 11:00 AM, 1:00 PM, and 3:30 PM on day 1 (untreated baseline), day 2 (timolol treatment alone), and days 3 through 5 (combination therapy with two drugs). One drop of 0.5% timolol was topically applied at 3:45 PM on day 1 and at 8:45 AM and 3:45 PM on days 2 through 5. One drop of 0.2% brimonidine or 2% dorzolamide or artificial tears was added on day 2 at 4:00 PM and at 9:00 AM and 4:00 PM on days 3 through 5, or latanoprost was added at 9:00 AM on days 3 through 5. Results: Compared with timolol alone, the maximal additive reduction in IOP which occurred on day 5 was 4.8 ± 0.8 mm Hg (mean ± standard error of the mean) with timolol plus brimonidine, 5.6 ± 1.0 mm Hg with timolol plus dorzolamide, 4.3 ± 1.0 mm Hg with timolol plus latanoprost, and 2.0 ± 0.5 mm Hg with timolol plus artificial tears (P < 0.01). At all measurements, timolol plus brimonidine, timolol plus dorzolamide, and timolol plus latanoprost caused greater (P < 0.05) IOP reductions than did timolol plus artificial tears. The additive IOP‐lowering effect was similar (P > 0.60) when comparing timolol plus brimonidine and timolol plus dorzolamide, timolol plus brimonidine and timolol plus latanoprost, timolol plus dorzolamide and timolol plus latanoprost at all measurements, but timolol plus dorzolamide caused a greater (P < 0.05) reduction of IOP than did timolol plus latanoprost at 0 hours on day 5. Conclusions: The addition of brimonidine, dorzolamide, or latanoprost to timolol caused similar additional reductions of IOP in glaucomatous monkey eyes.

Effect of flunarizine, a calcium channel blocker, on intraocular pressure and aqueous humor dynamics in monkeys.

PurposeTo evaluate the effects of flunarizine, a nonselective calcium channel blocker, on intraocular pressure (IOP) in monkeys with laser-induced unilateral glaucoma and on aqueous humor dynamics in normal monkeys. MethodsThe IOP was measured before and hourly for 6 hours after single-dose administration of 0.5%, 1%, or 2% flunarizine to the glaucomatous eye of 8 monkeys with unilateral laser-induced glaucoma. In a separate multiple-dose study, 0.5% flunarizine was applied twice daily for 5 consecutive days to the glaucomatous eye of the same 8 monkeys. IOP was measured at untreated baseline, after treatment with vehicle only, and on treatment days 1, 3, and 5. Tonographic outflow facility and fluorophotometric flow rates of aqueous humor were measured in 7 normal monkeys before and after the fifth dose of twice-daily treatment with 0.5% flunarizine. ResultsUnilateral application of 50 μL of 0.5%, 1%, or 2% flunarizine reduced IOP bilaterally. In the treated glaucomatous eyes, flunarizine reduced the IOP for 2, 3, or 5 hours, with a maximum reduction of 2.5±0.5 (mean±SEM) mm Hg (9%), 3.0±0.4 mm Hg (10%), and 5.0±0.8 mm Hg (18%) following the 0.5%, 1%, and 2% concentrations, respectively (P<0.01). The maximum reductions in IOP in the contralateral untreated eyes were 1.3±0.5 mm Hg, 1.5±0.3 mm Hg, and 2.9±0.7 mm Hg following the 0.5%, 1%, and 2% concentrations, respectively (P<0.05). Both the magnitude and duration of the ocular hypotensive effect of 0.5% flunarizine were enhanced with twice-daily administration for 5 days. Outflow facility in normal monkey eyes was increased (P<0.05) by 39% in the treated eyes compared with vehicle-treated contralateral eyes and by 41% compared with baseline values, and aqueous humor flow rates were unchanged (P>0.30). ConclusionsFlunarizine reduces IOP in a dose-dependent manner when administered to glaucomatous monkey eyes, but also has an ocular hypotensive effect on the contralateral untreated eyes. An increase in tonographic outflow facility seems to account for the IOP reduction in normal monkey eyes.

The effect of laser iridotomy on the anterior segment anatomy of patients with plateau iris configuration.

Purpose:To determine if laser iridotomy altered the anterior segment anatomy of patients with plateau iris configuration. Methods:Twenty eyes of 9 female and 1 male patients were imaged using an ultrasound biomicroscope within 19 weeks before and 52 weeks after laser iridotomy. Measurements obtained included the anterior chamber depth (ACD), trabecular-ciliary process distance (TCPD), iris thickness (IT), angle opening distance at 500 micrometers (AOD), iridozonular distance (IZD), and trabecular-iris angle (TIA). Comparisons of the pre- and post- iridotomy measurements were made using a two-tailed paired t test. Results:Laser iridotomy elicited no statistically significant change in ACD, TCPD, IT, AOD, or TIA. However, IZD was decreased (P < 0.05) in both eyes after laser iridotomy. Configuration of the irides was flat before and after laser iridotomies. Conclusion:This study suggests that laser iridotomy did not alter anterior segment anatomy, probably because of the fixed anterior insertion of the iris and ciliary body in plateau iris configuration. The decrease in IZD distance may be the result of a small posterior movement of the iris due to a reduction in relative pupillary block, secondary to laser iridotomy. The small reduction in relative papillary block in plateau iris configuration does not alter the width of the anterior chamber angle as measured by AOD and TIA.

Is intraocular pressure in the early postoperative period predictive of antimetabolite-augmented filtration surgery success?

Purpose:To determine whether intraocular pressure (IOP) in the early postoperative period after trabeculectomy or combined phacoemulsification-trabeculectomy, augmented with antimetabolite, correlates with IOP at one year in surgeries considered to be successful at that time point. Design:Retrospective case series. Methods:A chart review of antimetabolite-augmented surgical procedures done by DJG and JBS between January 1994 and November 2000 identified 82 primary or secondary trabeculectomies and 53 combined phacoemulsification-trabeculectomies with at least one year of follow-up. The success rate for each surgical subgroup was calculated and IOP on postoperative days (POD ± SD) 1, 7 (±2), 30 (±5), 90 (±10), and 180 (±20) was correlated with IOP at one year (POY 1, between month 12 and 15) using linear regression. IOP at each time point was compared among eyes that achieved success at one year with and without the use of IOP-lowering agents. Results:Of the 82 eyes having undergone antimetabolite-augmented trabeculectomies and the 53 eyes having undergone combined surgeries with at least one year of follow-up, the surgical success rates at POY 1 were 87.8% (72 of 82 eyes) and 92.5% (49 of 53 eyes). Of these, 42 eyes (58.3%) from 39 patients in the trabeculectomy group and 27 eyes (55.1%) from 24 patients in the combined surgery group did not require glaucoma medications at one year postsurgically, and were considered complete surgical successes. Mean preoperative IOP mm Hg ± SD was 26.0 ± 8.5 for the trabeculectomy group and 18.2 ± 4.5 for the phaco-trabeculectomy group. Postoperative IOP at POD 1, POD 7, POD 30, POD 90, POD 180, and POY 1 respectively for the eyes undergoing trabeculectomy were 13.9 ± 10.4, 9.5 ± 6.2, 12.0 ± 5.5, 12.0 ± 5.2, 12.8 ± 5.9, and 12.1 ± 4.3, and for the combined surgery group were 20.8 ± 12.5, 9.7 ± 5.7, 12.2 ± 5.4, 11.1 ± 3.4, 11.6 ± 4.6, and 10.3 ± 4.3. Intraocular pressure on postoperative day one correlated poorly with intraocular pressure at POY 1 for the trabeculectomy group (R2 = 0.0788), and not at all for the combined procedures group (R2 = 0.018). The correlation was slightly better for intraocular pressure at postoperative day 90 for the trabeculectomy group (R2 = 0.546), and at postoperative day 180 for the combined group (R2 = 0.37), but still rather low. Eyes requiring glaucoma medication use at POY 1 in the trabeculectomy group had higher (P < 0.009) intraocular pressure at POD 30 and at all subsequent visits than eyes not requiring these medications. Eyes requiring glaucoma medication use at POY 1 in the phaco-trabeculectomy group had higher (P < 0.0025) intraocular pressure at POD 30, POD 180, and POY 1 than eyes not requiring these medications. Conclusion:Intraocular pressure in the early postoperative period correlates very poorly with intraocular pressure one year after successful antimetabolite-augmented trabeculectomy or combined cataract extraction and trabeculectomy. Starting one month after glaucoma surgery, intraocular pressure is substantially lower in eyes that will ultimately not require the use of ocular hypotensive agents to achieve clinical success one year postoperatively.