Two-Year Experience With Latanoprostene Bunod in Clinical Practice.

PRECIS: We retrospectively reviewed records of patients prescribed latanoprostene bunod 0.024% (LBN) to assess its efficacy and safety in a real-world clinical setting. LBN was efficacious in lowering intraocular pressure (IOP) and had a favorable safety profile. PURPOSE: The aim of this study was to evaluate the usage of LBN, the first topical nitric oxide-donating prostaglandin analog (PGA) for reducing IOP, in clinical practice. PATIENTS AND METHODS: Retrospective review identified patients prescribed LBN by 5 glaucoma specialists at an academic center from January 2018 to November 2019. Fifty-six patients (102 eyes) met inclusion criteria of an IOP measured at the visit LBN was prescribed and at 2 visits ≥7 days after beginning treatment, with no surgeries, lasers or medication changes during follow-up. Main outcome measures were IOP, number of ocular medications, and adverse effects. RESULTS: IOP (mean±SD, mm Hg) at the visit LBN was prescribed was 16.2±4.3 on 3.2±1.5 glaucoma medications. IOP at most recent visit was 13.7±3.8 on 3.2±1.6 medications. Mean IOP reduction was 2.1±3.5 (P<0.0001) at first follow-up, after 38.7±36.5 days, and 2.5±3.3 (P<0.0001) at last follow-up, after 235.9±160.8 days. Pressure decreased ≥2 mm Hg in 60%, ≥3 mm Hg in 46%, and ≥4 mm Hg in 34% of eyes. All patients received LBN as replacement for a PGA or latanoprost/netarsudil fixed-dose combination. Forty-three patients remained on LBN throughout the follow-up period. Seven were discontinued for insufficient pressure control, 4 for adverse effects including pain and itching, and 2 for financial reasons. CONCLUSIONS: In 2 years of clinical use of LBN, patients exhibited IOP reductions that were statistically significant overall and clinically meaningful in 60% of patients. LBN was well-tolerated and may be more efficacious than traditional PGAs.

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

PURPOSE: To 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. METHODS: The 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. RESULTS: Unilateral application of 50 microL 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). CONCLUSIONS: Flunarizine 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.

Effect of 15-keto latanoprost on intraocular pressure and aqueous humor dynamics in monkey eyes.

PURPOSE: To compare the ocular hypotensive effects of 15-keto latanoprost (KL) with the commercial preparation of latanoprost (Xalatan; Pfizer, New York, NY) in monkey eyes with laser-induced unilateral glaucoma and to evaluate the effects of topical 0.005% KL on aqueous humor dynamics in normal monkey eyes. METHODS: Intraocular pressure (IOP) was measured hourly for 6 hours beginning at 9:30 AM on day 1 (untreated baseline); day 2 (vehicle only); and treatment days 1, 3, and 5 (topical, 30 microL of study drug) in the glaucomatous eyes of four to eight monkeys with unilateral laser-induced glaucoma. KL concentrations of 0.0001%, 0.001%, and 0.01% and latanoprost at 0.005% were studied separately, with a minimum washout period of 2 weeks between studies. Tonographic outflow facility (C) and fluorophotometric aqueous humor flow rates (F) were measured in nine normal monkeys before and after a single topical dose of 0.005% KL in one eye, with a vehicle-only control in the fellow eye. RESULTS: When applied once daily to glaucomatous monkey eyes, all three concentrations of KL and a 0.005% concentration of latanoprost produced significant (P < 0.05) reductions in IOP, with the maximum reduction on treatment day 5, regardless of the drug or concentration studied. The maximum reduction (P < 0.001) from vehicle-only baseline IOP was (mean +/- SEM) 3.0 +/- 0.3 mm Hg (9%) for 0.0001% KL, 7.6 +/- 0.6 mm Hg (23%) for 0.001% KL, 6.3 +/- 0.4 mm Hg (18%) for 0.01% KL, and 6.6 +/- 0.6 mm Hg (20%) for 0.005% latanoprost. After application of a single dose of 0.005% KL in nine normal monkey eyes, neither C nor F was altered (P > 0.80) when compared with untreated baseline values or vehicle-treated control eyes. CONCLUSIONS: The reduction in IOP produced by 0.001% KL was equivalent to, and at some measured time points, greater than the effect produced by 0.005% latanoprost. The IOP reduction by KL in normal monkeys appeared to have no effect on aqueous humor production or tonographic outflow facility and may thus indicate a drug-induced increase in uveoscleral outflow.

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.

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.

Additivity of bimatoprost or travoprost to latanoprost in glaucomatous monkey eyes.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.