Long-Term Safety and Efficacy of Perfluorohexyloctane Ophthalmic Solution for the Treatment of Patients With Dry Eye Disease: The KALAHARI Study.

PURPOSE: The aim of this study was to assess the long-term safety and efficacy of perfluorohexyloctane (PFHO) ophthalmic drop (formerly NOV03) for treatment of dry eye disease (DED). METHODS: KALAHARI was a phase 3, multicenter, single-arm, open-label extension study in patients aged 18 years or older with DED associated with Meibomian gland dysfunction who completed the randomized, double-masked, hypotonic saline-controlled GOBI study. Patients instilled 1 drop of PFHO (MIEBO, Bausch + Lomb) 4 times daily in both eyes for 52 weeks. Safety assessments included adverse events, best-corrected visual acuity, slit-lamp biomicroscopy, intraocular pressure, and dilated fundoscopy. Efficacy end points included change from GOBI study baseline in total corneal fluorescein staining and eye dryness score (0-100 visual analog scale). RESULTS: Overall, 208 patients from GOBI (PFHO [n = 97]; saline [n = 111]) were rolled over into KALAHARI. Twenty-nine patients (13.9%) had ≥1 ocular adverse event, with most being mild or moderate in severity; the most common ocular adverse events were vitreous detachment (1.9%), allergic conjunctivitis (1.4%), blurred vision (1.4%), and increased lacrimation (1.4%). Other safety end points were unremarkable. For patients continuing PFHO from GOBI, improvements in total corneal fluorescein staining and visual analog scale dryness scores observed in GOBI were maintained throughout KALAHARI. Patients treated with saline in GOBI and switched to PFHO in KALAHARI showed improvements in total corneal fluorescein staining and visual analog scale scores by week 4 that were maintained for the rest of the study. CONCLUSIONS: PFHO was safe and well tolerated and maintained efficacy for improving signs and symptoms of DED in this year-long study of patients with DED associated with Meibomian gland dysfunction.

Preservative-Free versus Benzalkonium Chloride-Preserved Latanoprost Ophthalmic Solution in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: A Phase 3 US Clinical Trial.

Purpose: To evaluate the safety and efficacy of a preservative-free latanoprost 0.005% formulation (T2345) in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT) compared to benzalkonium chloride-preserved latanoprost 0.005% (BPL) formulation in the United States (US). Patients and Methods: A prospective, randomized, multicenter, observer-masked, parallel-group study enrolled 335 patients diagnosed with POAG or OHT from 31 US sites who had adequately controlled intraocular pressure (IOP; ≤18 mm Hg) with latanoprost monotherapy. After a ≥72-hour washout period, patients were randomized to T2345 (n=165) or BPL (n=170) groups. Study drugs were dosed once-daily from Day 0 to Day 84 in one or both eyes. The study eye was the eye with lower IOP at baseline. The primary efficacy measure was the between-group comparison of the mean IOP values in the study eye at each time point (8 AM, 10 AM, and 4 PM on Days 15, 42, and 84). Safety measurements included ocular and systemic treatment-emergent adverse events (TEAEs). Results: Both T2345 and BPL adequately controlled IOP with 95% CIs within 1.5 mm Hg in the study eye at all assessed time points. The percentages of patients with diurnal IOP <18 mm Hg at Day 84 were 73.1% vs 78.7% for the T2345 and BPL groups, respectively. Adverse events were generally mild-to-moderate and primarily ocular. Fewer patients in the T2345 group experienced ocular TEAEs (13.9% vs 22.5%, respectively) and TEAEs with a suspected relationship to the study medication compared with the BPL group (5.5% vs 11.8%, respectively). The most common ocular TEAEs were instillation site pain and conjunctival hyperemia. Conclusion: In patients with POAG or OHT, both T2345 and BPL maintained IOP at or below clinically meaningful values for the duration of the study. T2345 showed a favorable safety profile, with numerically lower incidences of ocular TEAEs than BPL.

OCS-01 (Novel Topical Dexamethasone Formulation) in Inflammation and Pain Post Cataract Surgery: A Randomized, Double-Masked, Vehicle-Controlled Study.

PURPOSE: The goal of this study was to compare topical dexamethasone 1.5% in a novel formulation (OCS-01) once daily and BID versus vehicle for the treatment of inflammation and pain after cataract surgery. METHODS: This was a Phase II, double-masked, vehicle-controlled, randomized multicenter study. Adult patients with planned unilateral uncomplicated cataract surgery were randomized to receive OCS-01 once daily (n = 51), OCS-01 BID (n = 51), or matching vehicle (n = 51) for 15 days postsurgery. Primary end points were absence of anterior chamber cells (ACC; cells = 0) at Day 15 and absence of pain (score of "0") at postoperative Day 4. The Pearson χ2 test with a two-sided alpha = 0.1 was used to compare treatments. Safety was assessed in terms of adverse events and changes in intraocular pressure. FINDINGS: Treatment arms were generally similar in their baseline characteristics, with mean age ranging from 66 to 68 years, the proportion of male patients ranging from 29% to 37%, and 82% to 92% of each arm being White. On Day 15, a greater reduction in the percentage of eyes with ACC grade 0 was observed in the OCS-01 once daily (51%) and BID (66.7%) arms than in the vehicle arm (19.6%) (P = 0.0009 and P < 0.0001, respectively, using a Pearson χ2 test). On Day 4, the percentage of eyes with no pain was 72.5% (OCS-01 once daily), 62.7% (OCS-01 BID), and 45.1% (vehicle); statistical significance was reached for OCS-01 once daily (P = 0.005) and OCS-01 BID (P = 0.074) compared with vehicle. OCS-01 was well tolerated. A higher proportion of treatment-emergent adverse events, including ocular adverse events, were reported for the placebo group than for either OCS-01 group. IMPLICATIONS: OCS-01 once daily and BID were more effective than vehicle and well tolerated in the treatment of inflammation and pain after cataract surgery. CLINICALTRIALS: gov identifier: NCT04130802.

Safety of Once-Daily Oxymetazoline HCl Ophthalmic Solution, 0.1% in Patients with Acquired Blepharoptosis: Results from Four Randomized, Double-Masked Clinical Trials.

PURPOSE: An oxymetazoline 0.1% ophthalmic solution was recently approved for treatment of acquired blepharoptosis in adults. This study's objective was to evaluate the safety profile of oxymetazoline 0.1% when administered once daily for 14-84 days. PATIENTS AND METHODS: Pooled analysis examined safety outcomes from four randomized, double-masked, placebo-controlled clinical trials conducted at 6, 16, 27, and 35 sites, respectively, in the United States. In total, 568 participants with acquired blepharoptosis were evaluated. Median age was 66 years and 74.8% of participants were female. Overall, 375 participants self-administered oxymetazoline 0.1% to both eyes once/day and 193 self-administered placebo (vehicle) daily. Treatment-emergent adverse event (TEAE) rates, severity, and causality were evaluated in the overall population and within participant subgroups defined based on age, race, and ethnicity. Vital signs and ophthalmic findings were evaluated at predefined study visits. Patient-reported treatment tolerability was recorded at study end. RESULTS: TEAE incidence was similar among participants using oxymetazoline 0.1% (31.2%) or vehicle (30.6%). Nearly all TEAEs were mild-to-moderate, and most were not suspected of being treatment related. Serious TEAEs occurred in four participants receiving oxymetazoline 0.1% and one participant receiving vehicle. Nine and two participants in the oxymetazoline 0.1% and vehicle groups, respectively, discontinued due to a TEAE. Ocular TEAEs occurring in ≥2% of participants receiving oxymetazoline 0.1% were punctate keratitis, conjunctival hyperemia, dry eye, blurred vision, instillation site pain, and corneal vital dye staining, with none occurring in >3.5% of participants. TEAE rates were similar across subgroups based on age, race, and ethnicity. No clinically significant mean changes in vital signs or ophthalmologic findings occurred, and >98% of participants rated oxymetazoline 0.1% as causing no/mild discomfort. CONCLUSION: Once-daily oxymetazoline 0.1% was safe and well tolerated in participants with acquired blepharoptosis when used for 14-84 days. Safety did not appear to differ based on age, race, or ethnicity.

Rapid and Sustained Eyelid Elevation in Acquired Blepharoptosis with Oxymetazoline 0.1%: Randomized Phase 3 Trial Results.

PURPOSE: Oxymetazoline 0.1% is a novel ophthalmic agent for the treatment of acquired blepharoptosis in adults that has been shown to improve upper eyelid elevation and superior visual field deficits. This analysis characterized the rapid onset of upper eyelid elevation with once-daily oxymetazoline 0.1% and durability of this effect over 42 days. MATERIALS AND METHODS: Pooling data from two prospective, randomized, placebo-controlled, phase 3 studies, change in marginal reflex distance 1 (MRD-1) was evaluated at a range of post-instillation time points on treatment days 1, 14, and 42. Onset of effect was assessed beginning at 5 minutes post-administration (one study) and through 6 hours at the first two visits (both studies). Overall, 203 subjects received oxymetazoline 0.1% and 101 received vehicle. RESULTS: Oxymetazoline 0.1% demonstrated a rapid onset of action on all days evaluated. Mean changes from baseline 5 and 15 minutes post-oxymetazoline 0.1% instillation on day 1 were 0.59 ± 0.72 mm and 0.93 ± 0.81 mm, respectively (vs 0.20 ± 0.57 mm and 0.32 ± 0.64 mm with vehicle; both p<0.001). On day 14, mean changes from baseline 5 and 15 minutes post-oxymetazoline 0.1% instillation were 0.77 ± 0.85 mm and 1.11 ± 0.92 mm, respectively (vs 0.42 ± 0.78 mm and 0.41 ± 0.83 mm with vehicle; both p<0.05). This effect was also observed immediately post-instillation on day 42, where mean increases 5 and 15 minutes post-oxymetazoline 0.1% instillation were 0.86 ± 0.85 mm and 1.04 ± 0.91 mm, respectively (vs 0.42 ± 0.80 mm and 0.47 ± 0.93 mm with vehicle; both p<0.005). Significant improvements vs vehicle (p<0.001) were also observed at 2-6 hours on days 1 and 14. At all time points, the proportion of subjects showing a positive response to treatment (>0% MRD-1 increase) was >15% greater in the oxymetazoline 0.1% group (range 16.6-36.1% more responders vs vehicle), with the largest differences observed 2 and 6 hours post-instillation. CONCLUSION: Oxymetazoline 0.1% provided rapid and sustained upper eyelid elevation. Together with data demonstrating superior visual field improvement and a favorable safety profile, this analysis supports oxymetazoline 0.1% as an effective non-surgical treatment for acquired ptosis.

Topical lipoic acid choline ester eye drop for improvement of near visual acuity in subjects with presbyopia: a safety and preliminary efficacy trial.

OBJECTIVES: This study evaluated the safety of topical lipoic acid choline ester (UNR844, 1.5%) ophthalmic solution and its efficacy in improving distance-corrected near visual acuity (DCNVA) in subjects with presbyopia. SUBJECTS AND METHODS: This was a prospective, randomized, double-masked, and multicentre clinical trial. Subjects with a diagnosis of presbyopia (n = 75) were randomized 2:1 to UNR844 or placebo. On days 1-7, all subjects were dosed unilaterally (twice a day, b.i.d.) in their non-dominant eye to ensure safety and tolerability prior to days 8-91 when dosing was changed to bilateral (b.i.d.). Clinical assessments, including DCNVA and adverse events (AEs), were recorded at each study visit. Patients who completed the study were recruited into a non-interventional follow-up study that monitored them until 7 months after their final UNR844 exposure. The primary endpoints were safety and the mean change in DCNVA from baseline in the study eye. RESULTS: UNR844 administration (n = 50) produced no safety concerns and was well-tolerated, with no clinically-relevant changes in best-corrected distance visual acuity, pupil size, intraocular pressure, or discontinuations due to adverse events. DCNVA improved in the study eye in the UNR844 group compared to placebo during the 91 days of treatment [UNR844 vs. placebo, mean change in LogMAR (SD); -0.159 (0.120) vs. -0.079 (0.116)]. Bilateral DCNVA improved, with 53.1% UNR844 vs. 21.7% placebo subjects gaining ≥10 letters. Improvements in DCNVA were sustained at 5 and 7 months after UNR844 dosing ceased. CONCLUSIONS: These results support further development of UNR844 ophthalmic solution for the treatment of presbyopia.

Safety of KPI-121 Ophthalmic Suspension 0.25% in Patients With Dry Eye Disease: A Pooled Analysis of 4 Multicenter, Randomized, Vehicle-Controlled Studies.

PURPOSE: The safety of KPI-121 0.25%, an ophthalmic nanoparticle suspension of loteprednol etabonate, was evaluated in subjects with dry eye disease (DED) in one phase 2 and three phase 3 randomized trials of similar design. METHODS: Adults with DED received KPI-121 0.25% or vehicle drops 4 times daily (QID) for ≥2 weeks; 1430 subjects received KPI-121 0.25% and 1438 subjects received vehicle drops. Main safety assessments were adverse events (AEs) and intraocular pressure (IOP). As a common side effect associated with the use of ocular corticosteroids is elevated IOP, subjects with a history of or current diagnosis of glaucoma were excluded. RESULTS: Instillation site pain was the most common AE, reported by 5.2% of subjects in the KPI-121 0.25% group and 4.4% of subjects in the vehicle group; other AEs were reported by ≤0.8% of subjects in the KPI-121 group. IOP elevations, a side effect associated with the use of ophthalmic corticosteroids, were observed with low incidence: 0.6% and 0.2% of subjects in the KPI-121 and vehicle groups, respectively. An IOP elevation was defined as an increase from baseline of >5 mm Hg that resulted in an IOP of ≥21 mm Hg in either eye during use of the study product. CONCLUSIONS: KPI-121 ophthalmic suspension 0.25% seemed to be safe and well tolerated when dosed QID for 2 to 4 weeks in those DED subjects included in the 4 trials.

Association of Oxymetazoline Hydrochloride, 0.1%, Solution Administration With Visual Field in Acquired Ptosis: A Pooled Analysis of 2 Randomized Clinical Trials.

Importance: Treatment of acquired blepharoptosis (ptosis) is currently limited to surgical intervention. Objective: To examine the efficacy and safety of oxymetazoline hydrochloride, 0.1%, ophthalmic solution (oxymetazoline, 0.1%) in participants with acquired ptosis. Design, Setting, and Participants: This pooled analysis of 2 randomized, double-masked, placebo-controlled, multicenter phase 3 clinical trials included participants 9 years and older with acquired ptosis and superior visual field deficit. The 2 studies were conducted across 16 and 27 sites in the United States. Patients were enrolled from May 2015 to April 2019. Analyses for the individual trials were initiated after database lock and completed on September 6, 2017, and May 16, 2019. Pooled analysis was completed on August 25, 2019. Interventions: Participants (randomized 2:1) received oxymetazoline, 0.1%, or vehicle, self-administered as a single drop per eye, once daily, for 42 days. Main Outcomes and Measures: The primary efficacy end point was change from baseline in the number of points seen on the Leicester Peripheral Field Test, a test to detect superior visual field deficits due to ptosis, on days 1 (6 hours after instillation) and 14 (2 hours after instillation). The secondary end point, change from baseline in marginal reflex distance 1, was assessed at the same time points. Results: In total, 304 participants were enrolled (mean [SD] age, 63.8 [13.8] years; 222 women [73%]). Overall, 97.5% (198 of 203) of participants receiving oxymetazoline, 0.1%, and 97.0% (98 of 101) of participants receiving vehicle completed the studies. Oxymetazoline, 0.1%, was associated with a significant increase in the mean (SD) number of points seen on the Leicester Peripheral Field Test vs vehicle (day 1: 5.9 [6.4] vs 1.8 [4.1]; mean difference, 4.07 [95% CI, 2.74-5.39]; P < .001; day 14: 7.1 [5.9] vs 2.4 [5.5]; mean difference, 4.74 [95% CI, 3.43-6.04]; P < .001). Oxymetazoline, 0.1%, also was associated with a significant increase in marginal reflex distance 1 from baseline (mean [SD]: day 1: 0.96 [0.89] mm vs 0.50 [0.81] mm; mean difference, 0.47 mm [95% CI, 0.27-0.67]; P < .001; day 14: 1.16 [0.87] mm vs 0.50 [0.80] mm; mean difference, 0.67 mm [95% CI, 0.46-0.88]; P < .001). Treatment-emergent adverse events (TEAEs) occurred in 31.0% (63 of 203) of participants receiving oxymetazoline, 0.1%, and 35.6% (36 of 101) of participants receiving vehicle. Among participants receiving oxymetazoline, 0.1%, with a TEAE, 81% (51 of 63) had a maximum TEAE intensity of mild, and 62% (39 of 63) had no TEAE suspected of being treatment related. Conclusions and Relevance: Oxymetazoline, 0.1%, was associated with positive outcomes and was well tolerated in phase 3 trials after instillation at days 1 and 14, demonstrating its potential promise for the treatment of acquired ptosis, although further study is needed to elucidate the clinical relevance of these findings beyond 6 weeks.

Ophthalmic Drug Delivery Using Iontophoresis: Recent Clinical Applications.

Background: Iontophoresis is a noninvasive delivery system designed to overcome barriers to ocular penetration of topical ophthalmic medications by employing a low-amplitude electrical current to promote the migration of a charged drug substance across biological membranes. Trans-scleral iontophoresis of dexamethasone phosphate has demonstrated dramatically increased intraocular concentrations of dexamethasone in rabbit ocular tissues compared with topical instillation, including 50- to 100-fold greater aqueous humor concentrations. Methods: This article reviews available data on recent clinical applications of iontophoretic ophthalmic drug delivery. Results: The EyeGate II delivery system (EGDS) is a trans-scleral iontophoresis system that has been used in conjunction with EGP-437, a proprietary-charged formulation of dexamethasone phosphate for iontophoretic delivery. In patients with noninfectious anterior uveitis, EGP-437, delivered through 2 iontophoretic treatments using the EGDS, demonstrated similar efficacy to topical prednisolone acetate 1% eye drops instilled 8 times daily over 28 days, suggesting the potential to decrease or eliminate the need for daily dosing of topical steroids in this patient population. Other applications for EGP-437 delivered through the EGDS that have been explored in clinical trials include treatment of dry eye, postsurgical inflammation and pain, and scleritis. In addition, transcorneal iontophoresis has been used outside of the United States to enhance riboflavin penetration in patients undergoing corneal cross-linking as therapy for progressive keratoconus. Conclusions: The reviewed studies demonstrate the feasibility of using iontophoresis to enhance drug delivery to ocular tissues and support the potential of this noninvasive technique across a range of ophthalmic indications.

Iontophoretic Dexamethasone Phosphate Compared to Topical Prednisolone Acetate 1% for Noninfectious Anterior Segment Uveitis.

PURPOSE: To evaluate the safety and efficacy of dexamethasone phosphate ophthalmic solution (EGP-437) delivered by a transscleral iontophoresis delivery system (EyeGate II) compared to that of topical prednisolone acetate 1% (PA 1%) in subjects with noninfectious anterior uveitis. DESIGN: Prospective, randomized, double-masked, parallel group, noninferiority clinical trial. METHODS: A total of 193 subjects with active noninfectious anterior uveitis (anterior chamber [AC] cell count ≥11 cells) were randomized to EGP-437 delivered by iontophoresis (days 0 and 7) or self-administered PA 1% daily (tapered schedule, days 0-28). Masking was maintained with placebo iontophoresis or eye drops. The primary efficacy endpoint was the proportion of subjects with an AC cell count of zero on day 14. Noninferiority of EGP-437 was defined if the lower limit of the confidence interval (CI) for the difference (EGP-437 minus PA 1%) was less than -10%. RESULTS: At day 14, 32 of 96 EGP-437 subjects (33.3%) and 32 of 97 PA 1% subjects (33.0%) had an AC cell count of zero (difference, 0.34; 95% CI, -12.94 to 13.63; P = 0.064). Efficacy trended better with EGP-437 among patients with more severe baseline uveitis (AC cell count >25). Safety and tolerability were good with both treatments. EGP-437 subjects experienced fewer IOP elevations ≥6 mm Hg versus PA 1% subjects (13 vs 24 incidents, respectively, through day 28). CONCLUSIONS: Despite clinically similar response rates, statistical noninferiority of EGP-437 versus a tapered regimen of PA 1% was not achieved. Numerical trends suggesting fewer IOP elevations with EGP-437, similar efficacy overall, and possibly better efficacy in more severe disease warrant further study.

Multicenter Study of a Novel Topical Interleukin-1 Receptor Inhibitor, Isunakinra, in Subjects With Moderate to Severe Dry Eye Disease.

OBJECTIVES: Isunakinra, formerly known as EBI-005, is a novel interleukin (IL)-1 receptor inhibitor developed for topical treatment of patients with dry eye disease (DED). This phase 1b/2a multicenter, double-masked, randomized, vehicle controlled environmental trial assessed the safety and biological activity of isunakinra in patients with moderate to severe DED. METHODS: Subjects (N=74) were randomized to vehicle (placebo) or isunakinra (5 or 20 mg/mL) 3×/daily for 6 weeks. Evaluations included safety, tolerability, biological activity for signs (corneal fluorescein staining [CFS]), symptoms (pain or sore eyes and total Ocular Surface Disease Index [OSDI]), and reduction in rescue artificial tear use. RESULTS: Topical administration of isunakinra (5 and 20 mg/mL) was safe and well tolerated and resulted in clinically relevant improvements in symptoms (OSDI score, painful/sore eye component of OSDI) and signs (total CFS) compared with baseline with no dose response. OSDI scores improved from baseline by 38% (18.9 points) at 6 weeks and CFS scores improved by 33% (3 points) in the isunakinra groups. These changes were not statistically significant compared with the vehicle. Use of artificial rescue tears was significantly reduced in the isunakinra treatment groups (mean=9 vials) compared with vehicle (mean=31 vials). The differences between isunakinra and vehicle treatments were more pronounced in subjects with OSDI scores less than 50 at baseline. CONCLUSIONS: Isunakinra was safe, well tolerated and showed clinically meaningful improvements in signs and symptoms of DED. These results encouraged the design of an adequately powered study to characterize the safety and efficacy of isunakinra in ocular surface diseases.

A new device to noninvasively estimate the intraocular pressure produced during ocular compression.

PURPOSE: To describe a noninvasive instrument that estimates intraocular pressure during episodes of external globe compression and to demonstrate the accuracy and reliability of this device by comparing it to the intraocular pressures simultaneously and manometrically measured in cannulated eyes. METHODS: A thin fluid-filled bladder was constructed from flexible and inelastic plastic sheeting and was connected to a pressure transducer with high pressure tubing. The output of the pressure transducer was sent to an amplifier and recorded. This device was validated by measuring induced pressure in the fluid-filled bladder while digital pressure was applied to one surface, and the other surface was placed directly against a human cadaver eye or in vivo pig eye. The human cadaver and in vivo pig eyes were each cannulated to provide a manometric intraocular pressure control. RESULTS: The measurements obtained with the newly described device were within ~5% of simultaneously measured manometric intraocular pressures in both a human cadaver and in vivo pig eye model for a pressure range of ~15-100 mmHg. CONCLUSION: This novel noninvasive device is useful for estimating the intraocular pressure transients induced during any form of external globe compression; this is a clinical setting where no other devices can be used to estimate intraocular pressure.

Review of external ocular compression: clinical applications of the ocular pressure estimator.

PURPOSE: The authors have previously validated an Ocular Pressure Estimator (OPE) that can estimate the intraocular pressure (IOP) during external ocular compression (EOC). The authors now apply the OPE in clinical states where EOC is clinically important. The original work is described for two periods of risk: during sleep and during the digital ocular massage (DOM) maneuver used by surgeons after trabeculectomy to keep the operation functional. Other periods of risk for external ocular compression are then reviewed. METHODS: The first protocol estimated the IOP in the dependent eye during simulated sleep. Subjects had their IOPs initially measured in an upright-seated position, immediately upon assuming a right eye dependent side sleeping position (with nothing contacting the eye), and then 5 minutes later while still in this position. While maintaining this position, the fluid filled bladder of the OPE was then placed between the subject's closed eye and a pillow during simulated sleep. The IOP was continuously estimated in this position for 5 minutes. The subjects then had the IOP measured in both eyes in an upright-seated position. The second protocol determined if a larger vertical cup-to-disc ratio was more common on the side that patients reported they preferred to sleep on. The hypothesis was that chronic asymmetric, compression induced, elevations of IOP during sleep would be associated with otherwise unexplained asymmetry of the vertical cup-to-disc ratio. The third protocol assessed the IOP during DOM. The OPE was used to characterize the IOP produced during the DOM maneuver of five glaucoma surgeons. After this, 90 mmHg was chosen as a target pressure for DOM. The surgeons were then verbally coached during three additional compressions. After a 5-minute period, the surgeons were asked to reproduce this targeted IOP during subsequent compressions. RESULTS: The mean IOP during the "sleep session" was 22±5 mmHg (SEM). The mean peak pressure was 40±11 mmHg (SEM) and the mean trough pressure was 15±2 mmHg (SEM). There was a 78% agreement between the eye that was reported to be dependent during sleep and the eye with the larger vertical cup-to-disc ratio, for eyes with at least a 0.10 cup-to-disc ratio difference, P=0.001, n=137. The OPE estimated an average induced IOP during typical DOM of 104±8 mmHg (SEM), with each compression having an average range of 17±3 mmHg (SEM). After coaching, and a 5-minute waiting period, the average induced IOP reduced to 95±3 mmHg (SEM) with a reduced average range of IOP to 11±1 mmHg. CONCLUSION: The OPE was successfully used to estimate the IOP while subjects experienced EOC during normal sleep postures. These EOC-induced elevations of IOP were considerable, and likely contribute to significant ocular pathology, not only for glaucoma, but for retinal vascular occlusive diseases, retinal vascular leakage, and the induction of the ocular-cardiac reflex in infants, as well. The correlation of a larger vertical cup-to-disc ratio in patients with a sleep posture preference suggests a causal relationship, since patients with other conditions known to be associated with cup-to disc ratio asymmetry were excluded from this study. The OPE is a useful device to teach DOM to surgeons and patients for home use.

Evaluation of dexamethasone phosphate delivered by ocular iontophoresis for treating noninfectious anterior uveitis.

PURPOSE: Determine safe, effective, iontophoretic dose(s) of EGP-437 (dexamethasone phosphate formulated for iontophoresis) in patients with noninfectious anterior uveitis; evaluate systemic drug exposures. DESIGN: Prospective, phase I/II, multicenter, double-masked, parallel group, randomized clinical trial. PARTICIPANTS: Forty outpatients with anterior uveitis. METHODS: Forty of 42 randomized patients received an iontophoresis treatment in 1 qualifying eye and completed the study. Patients were randomized into 1 of 4 iontophoresis dose groups (1.6, 4.8, 10.0, or 14.0 mA-min), treated with EGP-437 via the EyeGate II Delivery System (EGDS), and followed until day 28. MAIN OUTCOME MEASURES: The main outcome measures were anterior chamber cell (ACC) scores at days 14 and 28; time to ACC score of zero; proportion of patients with an ACC score reduction from baseline of ≥ 0.5 at day 28; mean change from baseline in ACC score at day 28; and the systemic exposures of dexamethasone and dexamethasone phosphate after EGP-437 treatment with the EGDS. RESULTS: After a single EGP-437 treatment, 19 of 40 patients (48%) achieved an ACC score of zero at day 14. By day 28, 24 of 40 patients (60%) achieved an ACC score of zero. A Kaplan-Meier analysis demonstrated that the 1.6 mA-min dose was the most effective and revealed an inverse dose response; median days to an ACC score of zero were 11.5 days in the 1.6 mA-min group versus 31 days in the 14.0 mA-min group. Twenty-six patients (65%) had an ACC score reduction from baseline of ≥ 0.5 at day 28. The mean change in ACC score from baseline to day 28 was -2.14 with a median of -2.00. Throughout the study, the mean intraocular pressure remained within normal range and mean best-corrected visual acuity at 4 meters remained relatively stable. Most adverse events were mild; no serious adverse events were reported. Pharmacokinetics results showed low short-term systemic exposure to dexamethasone after iontophoresis; no nonocular systemic corticosteroid-mediated effects were observed. CONCLUSIONS: Approximately two thirds of the patients reached an ACC score of zero within 28 days, after only receiving 1 iontophoresis treatment. The lower doses seemed to be the most effective, and treatments were well-tolerated. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Difluprednate ophthalmic emulsion 0.05% for postoperative inflammation and pain.

PURPOSE: To assess the efficacy and safety of difluprednate ophthalmic emulsion 0.05% (Durezol) 2 or 4 times a day compared with those of a placebo in the treatment of inflammation and pain associated with ocular surgery. SETTING: Twenty-six clinics in the United States. METHODS: One day after unilateral ocular surgery, patients who had an anterior chamber cell grade of 2 or higher (>10 cells) were treated with 1 drop of difluprednate 2 times or 4 times a day or with a placebo (vehicle) 2 times or 4 times a day in the study eye for 14 days. This was followed by a 14-day tapering period and a 7-day safety evaluation. Outcome measures included cleared anterior chamber inflammation (grade 0, or=10 mm Hg and >or=21 mm Hg from baseline, respectively) versus 1% in the placebo group. CONCLUSIONS: Difluprednate given 2 or 4 times a day cleared postoperative inflammation and reduced pain rapidly and effectively. There were no serious ocular adverse events. Fewer adverse events were reported in the difluprednate-treated groups than in the placebo group.