Latanoprost-Eluting Contact Lenses in Glaucomatous Monkeys.

PURPOSE: To assess the ability of latanoprost-eluting contact lenses to lower the intraocular pressure (IOP) of glaucomatous eyes of cynomolgus monkeys. DESIGN: Preclinical efficacy study of 3 treatment arms in a crossover design. PARTICIPANTS: Female cynomolgus monkeys with glaucoma induced in 1 eye by repeated argon laser trabeculoplasty. METHODS: Latanoprost-eluting low-dose contact lenses (CLLO) and high-dose contact lenses (CLHI) were produced by encapsulating a thin latanoprost-polymer film within the periphery of a methafilcon hydrogel, which was lathed into a contact lens. We assessed the IOP-lowering effect of CLLO, CLHI, or daily latanoprost ophthalmic solution in the same monkeys. Each monkey consecutively received 1 week of continuous-wear CLLO, 3 weeks without treatment, 5 days of latanoprost drops, 3 weeks without treatment, and 1 week of continuous-wear CLHI. On 2 consecutive days before initiation of each study arm, the IOP was measured hourly over 7 consecutive hours to establish the baseline IOP. Two-tailed Student t tests and repeated-measures analysis of variance were used for statistical analysis. MAIN OUTCOME MEASURES: Intraocular pressure. RESULTS: Latanoprost ophthalmic solution resulted in IOP reduction of 5.4±1.0 mmHg on day 3 and peak IOP reduction of 6.6±1.3 mmHg on day 5. The CLLO reduced IOP by 6.3±1.0, 6.7±0.3, and 6.7±0.3 mmHg on days 3, 5, and 8, respectively. The CLHI lowered IOP by 10.5±1.4, 11.1±4.0, and 10.0±2.5 mmHg on days 3, 5, and 8, respectively. For the CLLO and CLHI, the IOP was statistically significantly reduced compared with the untreated baseline at most time points measured. The CLHI demonstrated greater IOP reduction than latanoprost ophthalmic solution on day 3 (P = 0.001) and day 5 (P = 0.015), and at several time points on day 8 (P < 0.05). CONCLUSIONS: Sustained delivery of latanoprost by contact lenses is at least as effective as delivery with daily latanoprost ophthalmic solution. More research is needed to determine the optimal continuous-release dose that would be well tolerated and maximally effective. Contact lens drug delivery may become an option for the treatment of glaucoma and a platform for ocular drug delivery.

Socioeconomic disparities in indoor air, breath, and blood perchloroethylene level among adult and child residents of buildings with or without a dry cleaner.

In many cities, dry cleaners using perchloroethylene are frequently located in multifamily residential buildings and often cause elevated indoor air levels of perchloroethylene throughout the building. To assess individual perchloroethylene exposures associated with co-located dry cleaners, we measured perchloroethylene in residential indoor air, and in blood and breath of adults and children residing in buildings with a dry cleaner as part of the New York City (NYC) Perc Project. We also measured perchloroethylene in indoor air, and in blood and breath of residents of buildings without a dry cleaner for comparison. Here, we evaluate whether an environmental disparity in perchloroethylene exposures is present. Study participants are stratified by residential building type (dry cleaner or reference) and socioeconomic characteristics (race/ethnicity and income); measures of perchloroethylene exposure are examined; and, the influence of stratified variables and other factors on perchloroethylene exposure is assessed using multivariate regression. All measures of perchloroethylene exposure for residents of buildings with a dry cleaner indicated a socioeconomic disparity. Mean indoor air perchloroethylene levels were about five times higher in minority (82.5 ug/m(3)) than in non-minority (16.5 ug/m(3)) households, and about six times higher in low-income (105.5 ug/m(3)) than in high income (17.8 ug/m(3)) households. Mean blood perchloroethylene levels in minority children (0.27 ng/mL) and adults (0.46 ng/mL) were about two and three times higher than in non-minority children (0.12 ng/mL) and adults (0.15 ng/mL), respectively. Mean blood perchloroethylene levels in low income children (0.34 ng/mL) and adults (0.62 ng/mL) were about three and four times higher than in high income children (0.11 ng/mL) and adults (0.14 ng/mL), respectively. A less marked socioeconomic disparity was observed in perchloroethylene breath levels with minority and low income residents having slightly higher levels than non-minority and high income residents. Multivariate regression affirmed that indoor air perchloroethylene level in dry cleaner buildings was the single most important factor determining perchloroethylene in blood and breath. Neither age, gender, nor socioeconomic status significantly influenced perchloroethylene levels in breath or blood. We previously reported that increased indoor air, breath, and blood perchloroethylene levels among NYC Perc Project child participants were associated with an increased risk for slightly altered vision. Thus, the disproportionately elevated perchloroethylene exposures of minority and low-income child residents of buildings with a dry cleaner shown here constitutes an environmental exposure disparity with potential public health consequences. Among residents of buildings without a dry cleaner, we observed some small increases in perchloroethylene breath and blood levels among non-minority or high income residents compared to minority or low income residents. These differences were not attributable to differences in indoor air levels of perchloroethylene which did not differ across socioeconomic categories, but appear to be associated with more frequent exposures dry cleaned garments.

The Role of Telemedicine in Glaucoma Care Triggered by the SARS-CoV-2 Pandemic: A Qualitative Study.

Purpose: To explore and report on how glaucoma care was impacted by the SARS-CoV-2 pandemic (COVID-19) in New York City (NYC) with a specific emphasis on the role of telemedicine. Patients and Methods: This was a qualitative, cross-sectional study that engaged glaucoma clinicians in semi-structured interviews to elicit perspectives on telemedicine and patient care experiences during the pandemic. Interview responses were coded and analyzed thematically. Results: Twenty clinicians participated. Mean participant age was 48.8 ± 12.3 years, and the mean number of years in practice post-glaucoma fellowship was 17.5 ± 12.4 years. Four main themes pertinent to the role of telemedicine triggered by the COVID-19 pandemic were identified: (1) The Need to Ensure Patient and Staff Safety Drove Telemedicine Uptake; (2) Telemedicine Allowed Providers to Address Subjective Complaints; (3) Telemedicine was Discontinued Due To Concerns of Compromised Patient Safety and Measurement Inaccuracy; (4) Technological Advances are Needed for Continued Telemedicine Usage and Uptake in Glaucoma Care. The interviews suggested that telemedicine usage dropped markedly within just a few months during the pandemic, and for most physicians interviewed, telemedicine is no longer part of their clinical practice. Several clinicians reported optimism towards future implementation of telemedicine as the technology develops. Conclusion: This study identified 4 themes outlining the uptake, application, discontinuation and overall perspectives on telemedicine by glaucoma clinicians. The role of telemedicine, as triggered by the COVID-19 pandemic, may have lasting implications for patient safety, continuity of care, and glaucoma care delivery beyond this public health crisis.

Effect of SPP 635, a renin inhibitor, on intraocular pressure in glaucomatous monkey eyes.

The effect of topical application of SPP 635, a renin inhibitor, on intraocular pressure (IOP) was evaluated in the eyes of monkeys with laser induced unilateral glaucoma. A multiple-dose study was performed in 8 glaucomatous monkey eyes with 3 concentrations of SPP 635, 0.2%, 0.3% and 0.4%. IOP was measured hourly for 6 h on each day of the study beginning at 9:30 a.m. Following one baseline day (untreated) and one vehicle-treated day (50 µl drop of vehicle to the glaucomatous eye at 9:30 a.m.), a 50 µl drop (25 µl × 2) of SPP 635, 0.2%, 0.3% or 0.4%, was topically applied to the glaucomatous eye at 9:30 a.m. and 3:30 p.m. for 5 consecutive days. Twice daily administration of each of the 3 concentrations of SPP 635 for 5 days significantly (p < 0.05) reduced IOP. The maximum reduction in IOP occurred 3 or 4 h after morning dosing and was 4.3 ± 0.8 (mean ± SEM) mmHg (14%) for 0.2% SPP 635, 5.3 ± 1.0 mmHg, (19%) for 0.3% SPP 635, and 8.0 ± 1.3 mmHg (25%) for 0.4% SPP 635. The longest duration of IOP reduction was for 6 h with 0.2% or 0.3% SPP 635, and was for at least 18 h with 0.4% concentration. Compared to 0.2% or 0.3% concentrations, 0.4% SPP 635 produced a greater (p < 0.05) and longer duration of IOP reduction (18 vs. 6 h). Mild conjunctival discharge appeared in 2 of 8 eyes, and hyperemia appeared in 2 eyes with the 0.3% and 0.4% concentrations on treatment days 3 and 5. Topically applied SPP 635, a new renin inhibitor, reduces IOP in glaucomatous monkeys in a dose-dependent manner. Renin inhibitors, are a novel class of compounds which may have potential for the treatment of glaucoma.

One-Year Randomized Comparison of Safety and Efficacy of Trabeculectomy with Mitomycin C Sub-Tenon Injection versus Mitomycin C-Infused Sponges.

PURPOSE: To compare the safety and efficacy of sub-Tenon injection of mitomycin C (MMC) with application of MMC-infused sponges during trabeculectomy. DESIGN: Single-center randomized clinical trial. PARTICIPANTS: A total of 56 eyes of 49 patients with open-angle glaucoma were included in this clinical trial. METHODS: In this single-center randomized clinical trial, 56 eyes of 49 patients underwent trabeculectomy with MMC for primary open-angle glaucoma. Patients were randomized into 2 groups. The injection group received a sub-Tenon injection of 0.15 ml of 0.01% MMC diluted with preservative free lidocaine 2% (n = 27). In the sponges group, sponges soaked in 0.02% MMC were applied under the Tenon's capsule and the scleral flap for 2 minutes (n = 29). Intraocular pressure, endothelial cell count, best-corrected visual acuity, and number of intraocular pressure (IOP)-lowering medications were assessed before surgery and 1 week; 1, 3, and 6 months; and 1 year after surgery. Complete success was defined as IOP of 14 mmHg or less without medication. Bleb morphologic features were assessed using the Indiana Bleb Appearance Grading Scale bleb grading system. MAIN OUTCOME MEASURES: Intraocular pressure reduction was the primary outcome. Bleb morphologic features and endothelial cell counts (ECCs) were secondary outcomes. RESULTS: Mean IOP in the sponges group decreased from 30.5 ± 7.4 mmHg at baseline to 12.6 ± 5.9 mmHg at 1 year (P < 0.001); in the injection group, IOP decreased from 29.3 ± 6.8 mmHg at baseline to 12.7 ± 4.3 mmHg at 1 year (P < 0.001). No difference in IOP between the 2 groups was noted at any visit (P < 0.001). Surgical success was 81.5% and 82.8% in the injection and sponges groups, respectively, at 1 year. Mean ECC values were unchanged from baseline to 1 year after surgery for both groups (P = 0.444). Complication rates were similar in the 2 groups. Bleb morphologic features showed differences in the appearance and grading of the blebs between the 2 groups at 1 year, showing larger extent, lower height, and less vascularization in the injection group. CONCLUSIONS: Sub-Tenon injection of MMC during trabeculectomy seems to be as safe and as efficacious as conventional application of MMC with sponges at 1 year after surgery. Bleb morphologic features show notable differences that may suggest a better long-term outcome.

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.

The Efficacy of the After-visit Summary in Medication Recall Among Glaucoma Patients.

PRéCIS:: To assess the after-visit summary (AVS) as a tool for glaucoma medication recall. Medication recall was associated with level of education and complexity of medication regimen. Receiving an AVS was not associated with better medication recall. PURPOSE: The purpose of this study was to determine whether patients given the AVS have better or worse glaucoma medication recall. MATERIALS AND METHODS: Observational clinical study. Adults on ≥1 glaucoma medications examined between June 30, 2017 and August 2, 2017. DATA COLLECTION: in-person questionnaire and retrospective chart review. Self-reported glaucoma medications compared with prescribed glaucoma medication regimen verified by electronic medical record. Medication recall assessed using 3-point scoring: 1 point each for; (1) name or color of bottle or cap; (2) treatment eye(s); and (3) dosing regimen. DATA ANALYSIS: 2-sample Welch t test, 2-proportion z-test, analysis of variance, univariate, and multivariate regression. RESULTS: A total of 118 patients enrolled: age 69.7±12.9 years (mean±SD), 55.9% of patients had received an AVS at the previous visit. Of these, 33.3% reported receiving an AVS, 51.2% reported not receiving one (15.1% did not recall or respond). Patients who had received AVSs had lower medication recall scores than those who did not (2.4±1.0 vs. 2.7±0.6, P=0.04). Receipt of an AVS was associated with having Nisha Chadha as their provider (P=0.01), fewer days since prior visit (P=0.0001), and medication regimen change at prior visit (P<0.0001). Multivariate analysis revealed completion of associate's degree or higher and fewer prescribed medications to be independent predictors of higher recall score (P=0.0002 and 0.002). CONCLUSIONS: AVSs were conceived to enhance patient care. This study indicates this goal is not achieved consistently. Less education and more complex medication regimens were identified as barriers to medication recall. Additional investigations should explore if modifying this document and enhanced explanation of its use will impact medication recall and health outcomes.

Netarsudil/Latanoprost Fixed-Dose Combination for Elevated Intraocular Pressure: Three-Month Data from a Randomized Phase 3 Trial.

PURPOSE: To compare the ocular hypotensive efficacy and safety of a fixed-dose combination (FDC) of the Rho kinase inhibitor netarsudil and latanoprost vs monotherapy with netarsudil or latanoprost. DESIGN: Three-month primary endpoint analysis of a randomized, double-masked, phase 3 clinical trial. METHODS: Adults with open-angle glaucoma or ocular hypertension (unmedicated intraocular pressure [IOP] >20 and <36 mm Hg at 8:00 AM) were randomized to receive once-daily netarsudil/latanoprost FDC, netarsudil 0.02%, or latanoprost 0.005% for up to 12 months. The primary efficacy endpoint was mean IOP at 8:00 AM, 10:00 AM, and 4:00 PM at week 2, week 6, and month 3. RESULTS: Mean treated IOP ranged from 14.8-16.2 mm Hg for netarsudil/latanoprost FDC, 17.2-19.0 mm Hg for netarsudil, and 16.7-17.8 mm Hg for latanoprost. Netarsudil/latanoprost FDC met the criteria for superiority to each active component at all 9 time points (all P < .0001), lowering IOP by an additional 1.8-3.0 mm Hg vs netarsudil and an additional 1.3-2.5 mm Hg vs latanoprost. At month 3, the proportion of patients achieving mean diurnal IOP ≤15 mm Hg was 43.5% for netarsudil/latanoprost FDC, 22.7% for netarsudil, and 24.7% for latanoprost. No treatment-related serious adverse events were reported; treatment-related systemic adverse events were minimal. The most frequent ocular adverse event was conjunctival hyperemia (netarsudil/latanoprost FDC, 53.4%; netarsudil, 41.0%; latanoprost, 14.0%), which led to treatment discontinuation in 7.1% (netarsudil/latanoprost FDC), 4.9% (netarsudil), and 0% (latanoprost) of patients. CONCLUSIONS: Once-daily netarsudil/latanoprost FDC demonstrated IOP reductions that were statistically and clinically superior to netarsudil and latanoprost across all 9 time points through month 3, with acceptable ocular safety.

Long-term Safety and Ocular Hypotensive Efficacy Evaluation of Netarsudil Ophthalmic Solution: Rho Kinase Elevated IOP Treatment Trial (ROCKET-2).

PURPOSE: To evaluate netarsudil 0.02% ophthalmic solution in patients with open-angle glaucoma (OAG) and ocular hypertension (OHT). DESIGN: Double-masked, randomized, multicenter, parallel-group, noninferiority clinical study. METHODS: After a washout of all prestudy ocular hypotensive medications, 756 eligible patients with elevated IOP were randomized to receive netarsudil 0.02% once a day (q.d.) (251); netarsudil 0.02% twice a day (b.i.d.) (254); or timolol 0.5% b.i.d. (251) for 12 months, as well as a noninterventional Corneal Observation Study (COS) for patients manifesting cornea verticillata. RESULTS: On treatment, mean IOP at 8:00 AM decreased from a baseline IOP of 22.5-22.6 mm Hg to 17.9-18.8 mm Hg, 17.2-18.0 mm Hg, and 17.5-17.9 mm Hg for netarsudil q.d., netarsudil b.i.d., and timolol, respectively, over 12 months. The most frequently reported adverse events (AEs) were ocular, with the most frequent ocular AE being conjunctival hyperemia, with an incidence of 61%, 66%, and 14%, respectively. The next most frequent AEs were corneal deposits (corneal verticillata), with an incidence of 26%, 25%, and 1%, respectively, and conjunctival hemorrhage (typically petechial), with an incidence of 20%, 19%, and 1%, respectively. All 3 AEs were generally scored as mild, with conjunctival hyperemia and/or hemorrhage appearing sporadically during the study. In the observational follow-up component of this study, there was no clinically meaningful impact of corneal verticillata on visual function in affected patients. CONCLUSIONS: In this randomized, double-masked trial, once-daily dosing of netarsudil 0.02% was effective, consistently lowering IOP through 12 months, and was tolerated by the majority of patients.

Once-Daily Netarsudil Versus Twice-Daily Timolol in Patients With Elevated Intraocular Pressure: The Randomized Phase 3 ROCKET-4 Study.

PURPOSE: To compare the intraocular pressure (IOP)-lowering efficacy and safety of netarsudil once daily (QD) and timolol twice daily (BID). DESIGN: Double-masked, randomized, phase 3, noninferiority study. METHODS: Patients with open-angle glaucoma or ocular hypertension (unmedicated baseline IOP >20 to <30 mm Hg at 8:00 AM) were randomized to netarsudil ophthalmic solution 0.02% QD (PM) or timolol ophthalmic solution 0.5% BID. The primary endpoint was mean IOP at 8:00 AM, 10:00 AM, and 4:00 PM at week 2, week 6, and month 3 in patients with baseline IOP <25 mm Hg (per-protocol population). Safety was recorded over the 6-month treatment period. RESULTS: A total of 186 patients from each treatment arm were included in the primary efficacy analysis. Netarsudil QD met the criteria for noninferiority to timolol BID. Mean treated IOP ranged from 16.3 to 17.9 mm Hg for netarsudil and 16.7 to 17.6 for timolol, with mean reductions from baseline of 3.9 to 4.7 mm Hg and 3.8 to 5.2 mm Hg, respectively. In prespecified secondary analyses, netarsudil demonstrated noninferiority to timolol in patients with baseline IOP <27 mm Hg and <30 mm Hg. The IOP-lowering effects of netarsudil were sustained over 6 months of treatment. No treatment-related serious adverse event (AE) was reported for either study drug. However, statistically significant reductions in mean heart rate were recorded at all study visits for the timolol group. The most frequent ocular AE among netarsudil-treated patients was conjunctival hyperemia (47.9%), which was predominately mild. CONCLUSIONS: Netarsudil QD (PM), a first-in-class IOP-lowering medication, was noninferior to timolol BID and was associated with tolerable ocular AEs.

The effect of selective laser trabeculoplasty on intraocular pressure in patients with intravitreal steroid-induced elevated intraocular pressure.

PURPOSE: To assess effectiveness of selective laser trabeculoplasty (SLT) in lowering intraocular pressure (IOP) in patients with steroid-induced elevated IOP. METHODS: Retrospective review of 7 patients (7 eyes) with IOP elevation after intravitreal triamcinolone acetonide (4.0 mg/0.1 mL) injections for macular edema (6 patients) or central retinal vein occlusion (1 patient). Three patients had preexisting open angle glaucoma; 2 patients had preexisting ocular hypertension. Time between intraocular corticosteroid injection and subsequent increased IOP ranged from 5 to 29 weeks. After unsuccessful maximum tolerated medical therapy, patients underwent unilateral SLT between April 2003 and June 2005. IOP was measured 4 weeks prelaser; on the day of laser; within 3 weeks, and at 1, 3, and 6 months postlaser. Two-sample t test was used for analysis. RESULTS: The pre-SLT and post-SLT IOP measurements were the major outcome measures used to define the relative success of the SLT procedure. Seven patients were taking 4.0+/-0.8 ocular hypotensive medications before SLT. Preoperative IOP (mm Hg+/-SD) 38.4+/-7.3 decreased postoperative to 25.6+/-7.1 within 3 weeks (P<0.003), 25.9+/-8.8 at 1 month (P<0.007), 23.9+/-10.6 at 3 months (P<0.006), and 15.7+/-2.2 at 6 months (P<0.001). Four patients underwent a second SLT procedure. Two patients failed after the 3-month visit. IOP in fellow eyes of all patients was unchanged (P>0.080). CONCLUSIONS: SLT lowered (P<0.007) IOP in 5 eyes of 7 patients with steroid-induced increased IOP from 3 weeks to 6 months postoperative. Two patients required additional surgical procedures. Repeat SLT treatments may be necessary. SLT is a temporizing procedure to consider in patients with steroid-induced elevated IOP.

Two Phase 3 Clinical Trials Comparing the Safety and Efficacy of Netarsudil to Timolol in Patients With Elevated Intraocular Pressure: Rho Kinase Elevated IOP Treatment Trial 1 and 2 (ROCKET-1 and ROCKET-2).

PURPOSE: To evaluate the efficacy and ocular and systemic safety of netarsudil 0.02% ophthalmic solution, a rho-kinase inhibitor and norepinephrine transporter inhibitor, in patients with open-angle glaucoma and ocular hypertension. DESIGN: Double-masked, randomized noninferiority clinical trials: Rho Kinase Elevated IOP Treatment Trial 1 and 2 (ROCKET-1 and ROCKET-2). METHODS: After a washout of all pre-study ocular hypotensive medications, eligible patients were randomized to receive netarsudil 0.02% once daily (q.d.), timolol 0.5% twice a day (b.i.d.), and (ROCKET-2 only) netarsudil 0.02% b.i.d. Data through 3 months from both studies are provided in this report. RESULTS: Enrolled into the 2 studies were 1167 patients. Treatment with netarsudil q.d. produced clinically and statistically significant reductions from baseline intraocular pressure (P < .001), and was noninferior to timolol in the per-protocol population with maximum baseline IOP < 25 mm Hg in both studies (ROCKET-2, primary outcome measure and population, ROCKET-1, post hoc outcome measure). Netarsudil b.i.d. was also noninferior to timolol (ROCKET-2). The most frequent adverse event was conjunctival hyperemia, the incidence of which ranged from 50% (126/251, ROCKET-2) to 53% (108/203, ROCKET-1) for netarsudil q.d., 59% (149/253, ROCKET-2) for netarsudil b.i.d., and 8% (17/208, ROCKET-1) to 11% (27/251, ROCKET-2) for timolol (P < .0001 for netarsudil vs timolol). CONCLUSIONS: In 2 large, randomized, double-masked trials reported here, once-daily dosing of netarsudil 0.02% was found to be effective and well tolerated for the treatment of patients with ocular hypertension and open-angle glaucoma. The novel pharmacology and aqueous humor dynamic effects of this molecule suggest it may be a useful addition to the armamentarium of ocular hypotensive medications.

A multicenter, retrospective pilot study of resource use and costs associated with severity of disease in glaucoma.

OBJECTIVE: To examine resource consumption and the direct costs of treating glaucoma at different disease severity levels. DESIGN: Observational, retrospective cohort study based on medical record review. PARTICIPANTS: One hundred fifty-one records of patients with primary open-angle or normal-tension glaucoma, glaucoma suspect, or ocular hypertension (age > or =18 years) were randomly selected from 12 sites in the United States and stratified according to severity based on International Classification of Diseases, Ninth Revision, Clinical Modification codes. Patients had to have been followed up for a minimum of 5 years. Patients with concomitant ocular disease likely to affect glaucoma treatment-related resource consumption were excluded. METHODS: Glaucoma severity was assessed and assigned using a 6-stage glaucoma staging system, modified from the Bascom Palmer (Hodapp-Anderson-Parrish) system. Clinical and resource use data were collected from the medical record review. Resource consumption for low-vision care and vision rehabilitation was estimated for patients with end-stage disease based on specialist surveys. For each stage of disease, publicly available economic data were then applied to assign resource valuation and estimate patient-level direct costs from the payer perspective. MAIN OUTCOME MEASURES: Average annual resource use and estimated total annual direct cost of treatment were calculated at the patient level and stratified by stage of disease. Direct costs by specific resource types, including ophthalmology visits, glaucoma surgeries, medications, visual field examinations, and other glaucoma services, were also assessed. RESULTS: Direct ophthalmology-related resource use, including ophthalmology visits, glaucoma surgeries, and medication use, increased as disease severity worsened. Average direct cost of treatment ranged from $623 per patient per year for glaucoma suspects or patients with early-stage disease to $2511 per patient per year for patients with end-stage disease. Medication costs composed the largest proportion of total direct cost for all stages of disease (range, 24%-61%). CONCLUSIONS: The study results suggest that resource use and direct cost of glaucoma management increase with worsening disease severity. Based on these findings, a glaucoma treatment that delays the progression of disease could have the potential to significantly reduce the health economic burden of this chronic disease over many years.

Ocular Hypotensive Effect of ONO-9054, an EP3/FP Receptor Agonist: Results of a Randomized, Placebo-controlled, Dose Escalation Study.

PURPOSE: To assess pharmacodynamic and safety profiles of ONO-9054 following single and multiple day dosing in subjects with ocular hypertension or open-angle glaucoma. MATERIALS AND METHODS: This was a phase I, single-center, randomized, double-masked, placebo-controlled dose-escalation study. Nine subjects were randomized to each of ONO-9054 3, 10, 20, 30 µg/mL and 12 to placebo. Subjects received a single drop to each eye at 07:00±30 minutes (single dose). Following a 4-day no-treatment period, subjects were dosed once daily for 14 consecutive days (multiple day dosing). Intraocular pressure (IOP) was measured regularly and compared with baseline measurements. Ocular examinations assessed safety and tolerability. RESULTS: Mean IOP decreased dose dependently. Following single dosing, IOP decreased from 22.9±4.0 to 15.9±2.3 mm Hg (ONO-9054, 30 µg/mL) at peak effect 9 hours postdose; the reduction in placebo-treated subjects was from 22.3±2.4 to 21.5±3.3 mm Hg. Following multiple day dosing, the greatest reduction in IOP occurred 1 hour postdose on day 18, from 23.3±0.6 to 15.1±2.4 mm Hg (ONO-9054, 10 µg/mL); the smallest reduction at this time was from 23.9±0.8 to 18.6±2.0 mm Hg (ONO-9054, 3 µg/mL). Pressures remained reduced on day 19, 25 hours after the last dose, when the lowest measurement was 15.8±2.1 mm Hg (ONO-9054, 10 µg/mL). Anterior uveitis and vitreous detachment were each reported in 2 subjects and considered moderate by the Investigator. Ocular hyperemia and tolerability symptoms were generally mild and transient. CONCLUSIONS: ONO-9054 was well-tolerated and elicited dose-dependent reductions in IOP, which were sustained for at least 24 hours following 2 weeks of consecutive daily dosing.

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 pilocarpine to bimatoprost in ocular hypertension and early glaucoma.

PURPOSE: To determine if the intraocular pressure (IOP) effect of pilocarpine at various concentrations is additive to that of bimatoprost and to assess the tolerability of this combination. METHODS: This was a randomized, prospective trial of patients with IOP > 21 mm Hg following appropriate medication washout. For all visits IOP was measured at 9:00 AM and 11:00 AM. Following baseline visit (#1), bimatoprost 0.03% was instilled qhs OU through visit 6. Following visits 2, 3, and 4 pilocarpine (2%, 4%, 6%) was instilled qid in one randomly selected eye. Pilocarpine was discontinued after visit 5 and bimatoprost after visit 6. Two-tailed, paired t test was used to compare treated and contralateral eyes for their IOP, IOP change, percentage IOP change from baseline, and to compare IOP in the same eye at 9:00 AM and 11:00 AM (before and after pilocarpine administration). IOPs using bimatoprost alone or in combination with various pilocarpine concentrations were compared using single variant Analysis of Variance (ANOVA). RESULTS: Seventeen patients were enrolled and 13 patients completed the study. Bimatoprost reduced IOP 28.7% to 30.5% (P < 0.0001) from baseline to visit 2. IOPs in eyes treated with bimatoprost alone or with bimatoprost and various pilocarpine concentrations were similar (P > 0.81, ANOVA). The IOP (P > 0.17) and percentage IOP change from baseline (P > 0.10) was similar in treated and contralateral eyes with all three strengths of pilocarpine. IOP values at 9:00 AM and 11:00 AM, before and after pilocarpine administration, were similar (P > 0.22). CONCLUSION: Bimatoprost alone reduces IOP substantially. Pilocarpine added to bimatoprost at concentrations of 2%, 4%, or 6% was neither additive nor antagonistic to the ocular hypotensive efficacy of bimatoprost.

Can Visual Field Progression be Predicted by Confocal Scanning Laser Ophthalmoscopic Imaging of the Optic Nerve Head in Glaucoma? (An American Ophthalmological Society Thesis).

PURPOSE: To determine whether confocal scanning laser ophthalmoscopic imaging (Heidelberg retinal tomography [HRT]) can predict visual field change in glaucoma. METHODS: The study included 561 patients with glaucoma or ocular hypertension whose clinical course was followed at the Mount Sinai Faculty practice. Humphrey visual fields (HVFs) and HRT images were collected on one randomly selected eye per patient. Glaucoma progression was determined by the presence of two sequential statistically significant negative slopes in mean deviation (MD) or visual field index (VFI) at any point during the study period. Trend-based analysis on HRT parameters was used to determine progressive changes and whether these occurred before or after HVF change. Sensitivity and specificity of HRT to predict HVF change were calculated. HVF rate of change was correlated to the rate of change detected by HRT imaging. RESULTS: Approximately 17% of patients progressed by either MD or VFI criteria. MD and VFI correlated highly and identified overlapping sets of patients as progressing. HRT global parameters had poor sensitivity (∼42%) and moderate specificity (∼67%) to predict HVF progression. Regional stereometric parameters were more sensitive (69%-78%) but significantly less specific (24%-27%). Sensitivity of global stereometric parameters in detecting HVF change was not significantly affected by the level of visual field damage (P=.3, Fisher exact test). HVF rate of change did not correlate with rate of change of HRT parameters. CONCLUSIONS: Trend-based analysis of HRT parameters has poor sensitivity and specificity in predicting HVF change. This may be related specifically to HRT imaging or may reflect the fact that in some patients with glaucoma, functional changes precede structural alterations.

Effect of 0.04% AR-13324, a ROCK, and norepinephrine transporter inhibitor, on aqueous humor dynamics in normotensive monkey eyes.

PURPOSE: To determine the mechanism by which topically applied AR-13324, a rho kinase inhibitor, and an inhibitor of the norepinephrine transporter, reduces intraocular pressure (IOP) in normotensive monkey eyes. METHODS: Seven normotensive monkeys were used. Tonographic outflow facility (C) was measured before drug administration and repeated 6 hours after administration of 50 µL (25 µL×2) of 0.04% AR-13324 to 1 eye and an equal volume of vehicle to the contralateral control eye. Baseline aqueous humor flow rates (F) were measured hourly for 6 hours beginning at 10:00 AM on day 1. On day 2, 50 µL (25 µL×2) of 0.04% AR-13324 was applied to 1 eye of each animal and vehicle to the fellow eye at 8:00 AM. Aqueous humor flow rates were measured at the same times as on the baseline day beginning 2 hours after dosing. RESULTS: Six hours after a single dose of 0.04% AR-13324 to 7 normal monkey eyes, C was increased (P<0.05) by 53% in drug-treated eyes compared with either contralateral vehicle-treated control eyes or baseline measurements. The IOP measured by pneumatonometer in treated eyes was reduced (P<0.005) by 25% when compared with baseline measurements and by 24% when compared with contralateral vehicle-treated eyes. For 6 hours after a single dose of 0.04% AR-13324, F was reduced (P<0.05) by 20% and 23% when compared with contralateral vehicle-treated eyes and baseline values, respectively. CONCLUSIONS: AR-13324 reduces IOP in normotensive monkey eyes. A dual mechanism of action, increase in tonographic outflow facility, and decrease of aqueous humor flow rates, accounts for the IOP reduction in normotensive monkey eyes.