A Phase IIa Multicenter, Randomized, Vehicle-Controlled, Dose Escalating Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of CBT-001 Ophthalmic Solution in Patients With Primary or Recurrent Pterygium.

Purpose: To evaluate the safety and efficacy of CBT-001, a multitarget tyrosine kinase inhibitor eyedrop, for pterygia. Design: Phase II clinical trial. Stage 1 was a single center, open-labeled, vehicle-controlled study. Stage 2 was a multicenter, randomized, double-masked, vehicle-controlled trial. Participants: Patients with primary or recurrent pterygia. Main Outcome Measures: The primary efficacy end point was lesion vascularity based on masked grading of photographs by an independent reading center. Other end points included dimensions of pterygia and safety. Methods: In stage 1, 24 eyes of 24 patients received 1 drop of CBT-001 in a dose escalation fashion (0.02%, 0.05%, and 0.2%) to determine the maximally tolerated dose based on adverse events (AEs) and blood drug levels. In stage 2, subjects were randomly assigned to receive the maximally tolerated dose of CBT-001 or vehicle dosed 3 times a day for 4 weeks with a 20-week follow-up. Results: In stage 1, the plasma maximum concentration values for all doses of CBT-001 were at or below the limit of detection (0.01 ng/ml). The most commonly reported AEs were mild foreign body sensation and irritation. CBT-001 0.2% was evaluated in stage 2. Baseline demographic characteristics were similar between patients receiving CBT-001 (n = 25) and vehicle (n = 23). After 4 weeks of dosing, the mean change from baseline in pterygium vascularity scores was -0.8 ± 0.7 (mean ± standard deviation) in subjects receiving CBT-001 0.2% and 0.0 ± 0.5 in subjects receiving vehicle (P < 0.001; 95% confidence interval: -1.12, -0.40). Pterygium vascularity scores remained significantly decreased, after the 4-week dosing period, at weeks 8 and 16, but not at week 24. The mean changes from baseline in the length of the pterygia were also significantly lower in subjects receiving CBT-001 compared with vehicle at weeks 2, 4, and 8 (P ≤ 0.014). The most commonly reported AEs were ocular, mild in severity, resolved after therapy, and did not result in discontinuation. Conclusions: CBT-001 0.2% decreased pterygia vascularity and lesion length after 4 weeks of dosing with a prolonged effect after dosing. The drug was well tolerated with minimal detected systemic drug levels. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Performance of a Translucent Activator for LipiFlow Vectored Thermal Pulse (VTP) Treatment of Meibomian Gland Dysfunction.

Purpose: Investigator feedback was used to assess the clinical use of the LipiFlow® System with the new translucent Activator Clear to successfully complete LipiFlow® treatments. Patients and Methods: This was a prospective, open-label clinical investigation. A total of 88 eyes (44 subjects) were treated using the LipiFlow® System with the new Activator Clear. Subjects diagnosed with bilateral meibomian gland dysfunction (MGD) were enrolled in the study. Each investigator performed a complete LipiFlow® treatment with the translucent Activator on both eyes of each subject. Investigators completed a questionnaire assessing the clinical use of the Activator Clear on a 5-point scale (1 - very difficult or strongly disagree, 3 - neutral, 5 - very easy or strongly agree). Results: The new translucent Activator provided successful LipiFlow® treatments in 100% of cases, with 95% confidence interval of (96%, 100%). Additionally, the investigators agreed or strongly agreed that the translucent components of the Activator Clear made it easy to access and position the activator with confidence on the subject's eye. Conclusion: The overall investigators' impressions on usage and functionality of LipiFlow® System with the translucent Activator were very positive. The Activator Clear enables doctors with efficient and confident positioning around patient eyelids to ensure successful LipiFlow® treatment when used as indicated.

Safety and effectiveness of a new ophthalmic viscosurgical device: randomized, controlled study.

PURPOSE: To evaluate the safety and effectiveness of a new dispersive ophthalmic viscosurgical device (OVD) (ClearVisc) compared with an approved dispersive OVD (Viscoat) when used in cataract surgery. SETTING: 16 clinics in the United States. DESIGN: Prospective multicenter controlled randomized 1:1 (ClearVisc:Viscoat; stratified by site, age group, and cataract severity). Patients and examiners masked. METHODS: Patients aged 45 years or older with age-related noncomplicated cataract considered amenable to treatment with standard phacoemulsification cataract extraction and intraocular lens (IOL) implantation were included. Patients were randomized to receive either ClearVisc or Viscoat using standard techniques. 5 postoperative visits occurred at 6 hours, 24 hours, 7 days, 1 month, and 3 months. The primary effectiveness outcome was the change in endothelial cell density (ECD) from baseline to 3 months. The primary safety end point was the proportion of patients who experienced at least 1 intraocular pressure (IOP) measurement ≥30 mm Hg at any follow-up visit. Noninferiority was tested. Inflammation and adverse events were evaluated. RESULTS: 372 patients were randomized: 184 patients in the ClearVisc group and 188 patients in the Viscoat group. ClearVisc was noninferior to Viscoat in mean percentage of ECD loss from baseline to 3 months (8.4% and 6.8%, respectively). ClearVisc was significantly noninferior to Viscoat in the proportion of patients with postoperative IOP ≥30 mm Hg at any follow-up visit (17.4% and 20.3%, respectively, P = .0002). CONCLUSIONS: ClearVisc dispersive OVD provides surgeons with a new option in the continuum of approved dispersive OVDs with beneficial properties as a surgical aid in cataract extraction and IOL implantation.

Safety and efficacy of amniotic cytokine extract in the treatment of dry eye disease.

Purpose: Evaluate the safety and efficacy of cryopreserved amniotic cytokine extract (ACE) in the treatment of subjects with dry eye disease (DED). Patients and methods: This was a retrospective, multicenter, chart review of adult patients with DED that instilled cryopreserved ACE drops twice-daily for 4 or 12 weeks. Patients had corneal fluorescein staining (0-20 range) and/or a lissamine green conjunctival staining score (0-18 range) of ≥3 and ≤9 in at least 1 eye and a score ≥40 (0-100 range) of eye dryness/irritation on a visual analog scale (VAS). Following completion of a treatment course, medical records were reviewed from the initiation of therapy (baseline), and at post-treatment visits (4 weeks, 8 weeks, and 12 weeks). Patient records for visual acuity, adverse events, corneal fluorescein staining, conjunctival lissamine green staining, and symptom scores of ocular dryness/irritation were reviewed for each visit, as available. Safety and tolerability were assessed through the evaluation of patient-reported adverse events recorded in the medical records. Results: A total of 54 eligible patients were identified at 7 clinical sites; 16 patients administered ACE drops for 4-weeks, and 38 patients instilled ACE drops for 12 weeks. Significant improvements in the mean changes from baseline were observed for corneal fluorescein staining, lissamine green staining, visual acuity (LogMar) and VAS ocular symptom scores at the 4-week post-treatment visit (p<0.01). Additional improvements continued out to the 12-week follow-up assessment visits. Two patients discontinued therapy due to reports of ocular burning or foreign body sensation. Conclusion: The cryopreserved ACE formulation was well-tolerated and effective in reducing the clinical signs and symptoms of DED. Conduct of a vehicle-controlled prospective study is warranted.

A Phase 3, Randomized, Double-Masked Study of OTX-101 Ophthalmic Solution 0.09% in the Treatment of Dry Eye Disease.

PURPOSE: To evaluate the safety and efficacy of OTX-101, a novel aqueous nanomicellar formulation of cyclosporine (0.09%), in the treatment of patients with dry eye disease (DED). DESIGN: A randomized, multicenter, vehicle-controlled, double-masked, phase 3 clinical trial. PARTICIPANTS: Adults (18-90 years of age) with a history and clinical diagnosis of DED, a global symptom score of 40 or more (range, 0-100), and a lissamine green conjunctival staining score of 3 or more and 9 or less (range, 0-12) in at least 1 eye. METHODS: Eligible patients entered a run-in period of 14 to 20 days in which all patients administered vehicle twice daily. Patients who remained eligible at the baseline (day 0) visit were randomized in a 1:1 ratio to twice-daily treatment with OTX-101 0.09% or vehicle for 84 days. MAIN OUTCOME MEASURES: Efficacy assessments included signs (unanesthetized Schirmer tear test, corneal and conjunctival staining) and symptoms (global symptom score) of DED. The primary end point was the proportion of eyes with a clinically meaningful improvement (increase of ≥10 mm) in Schirmer test score at day 84. Safety evaluations included adverse events (AEs), visual acuity, and intraocular pressure monitoring, slit-lamp, dilated ophthalmoscopy, and fundus examinations. RESULTS: A total of 744 patients were randomized and received study medication (371 to OTX-101 0.09% and 373 to vehicle). The primary end point was achieved; a significantly greater percentage of eyes in the OTX-101 0.09% treatment group achieved an increase of 10 mm or more in the Schirmer test score at day 84 (OTX-101 0.09%, 16.6%; vehicle, 9.2%; P < 0.001). Significant improvements relative to vehicle also were observed for corneal (days 28, 56, and 84) and conjunctival (days 56 and 84) staining. The global symptom score was reduced from baseline in both treatment groups by approximately 30%; however, no significant separation between groups was observed. The OTX-101 0.09% formulation was well tolerated. Treatment-emergent AEs were primarily mild in intensity. CONCLUSIONS: Clinically and statistically significant improvements in tear production and ocular surface integrity were observed in patients treated with OTX-101 0.09% for DED.

Multicenter randomized phase 3 study of a sustained-release intracanalicular dexamethasone insert for treatment of ocular inflammation and pain after cataract surgery.

PURPOSE: To assess the efficacy and safety of a sustained-release intracanalicular dexamethasone insert for the treatment of postoperative ocular inflammation and pain in patients having cataract surgery. SETTING: Twenty-one United States sites. DESIGN: Prospective multicenter randomized parallel-arm double-masked vehicle-controlled phase 3 study. METHODS: Patients with planned clear corneal cataract surgery were randomized (1:1) to receive dexamethasone insert or placebo, and the treatment was placed in the canaliculus of the eye immediately after surgery (Day 1). The primary efficacy endpoints were complete absence of anterior chamber cells at Day 14 and complete absence of pain at Day 8. RESULTS: The study comprised 438 adult patients (216 in the treatment arm and 222 in the placebo arm). At Day 14, significantly more patients had an absence of anterior chamber cells in the dexamethasone insert arm compared with placebo (52.3% versus 31.1%; P < .0001). At Day 8, significantly more patients had an absence of ocular pain in the dexamethasone insert arm compared with placebo (79.6% versus 61.3%; P < .0001). The dexamethasone insert arm showed no increase compared with placebo in incidence of all adverse events or ocular adverse events. Twice as many placebo patients required rescue therapy, compared with treated patients at Day 14. CONCLUSIONS: Both primary endpoints were successfully met. In addition, patients receiving the dexamethasone insert experienced a decrease in inflammation after surgery as early as Day 4 through Day 45, and a decrease in pain as early as one day after surgery (Day 2) through Day 45. The dexamethasone insert was well-tolerated, and the adverse events profile was similar to placebo.

The Prospective Health Assessment of Cataract Patients' Ocular Surface (PHACO) study: the effect of dry eye.

PURPOSE: To determine the incidence and severity of dry eye as determined by the International Task Force (ITF) scale in patients being screened for cataract surgery. PATIENTS AND METHODS: This was a prospective, multi-center, observational study of 136 patients, at least 55 years of age, who were scheduled to undergo cataract surgery. The primary outcome measure was the incidence of dry eye as evaluated by grade on the ITF scale and secondary outcome measures include tear break-up time (TBUT), ocular surface disease index score, corneal staining with fluorescein, conjunctival staining with lissamine green, and a patient questionnaire to evaluate symptoms of dry eye. RESULTS: Mean patient age was 70.7 years. A total of 73.5% of patients were Caucasian and 50% were female. Almost 60% had never complained of a foreign body sensation; only 13% complained of a foreign body sensation half or most of the time. The majority of patients (62.9%) had a TBUT ≤5 seconds, 77% of eyes had positive corneal staining and 50% of the eyes had positive central corneal staining. Eighteen percent had Schirmer's score with anesthesia ≤5 mm. CONCLUSION: The incidence of dry eye in patients scheduled to undergo cataract surgery in a real-world setting is higher than anticipated.

Dysfunctional tear syndrome: dry eye disease and associated tear film disorders - new strategies for diagnosis and treatment.

Dysfunctional tear syndrome (DTS) is a common and complex condition affecting the ocular surface. The health and normal functioning of the ocular surface is dependent on a stable and sufficient tear film. Clinician awareness of conditions affecting the ocular surface has increased in recent years because of expanded research and the publication of diagnosis and treatment guidelines pertaining to disorders resulting in DTS, including the Delphi panel treatment recommendations for DTS (2006), the International Dry Eye Workshop (DEWS) (2007), the Meibomian Gland Dysfunction (MGD) Workshop (2011), and the updated Preferred Practice Pattern guidelines from the American Academy of Ophthalmology pertaining to dry eye and blepharitis (2013). Since the publication of the existing guidelines, new diagnostic techniques and treatment options that provide an opportunity for better management of patients have become available. Clinicians are now able to access a wealth of information that can help them obtain a differential diagnosis and treatment approach for patients presenting with DTS. This review provides a practical and directed approach to the diagnosis and treatment of patients with DTS, emphasizing treatment that is tailored to the specific disease subtype as well as the severity of the condition.

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.

The efficacy of bromfenac ophthalmic solution 0.07% dosed once daily in achieving zero-to-trace anterior chamber cell severity following cataract surgery.

PURPOSE: To evaluate the efficacy of bromfenac ophthalmic solution 0.07% dosed once daily in achieving zero-to-trace (0-5 cells) anterior chamber cells, following cataract surgery with posterior chamber intraocular lens implantation. METHODS: The study designed employed two Phase III, double-masked, placebo-controlled, multicenter clinical trials of 440 subjects, randomized to either bromfenac ophthalmic solution 0.07% (n=222) or placebo (n=218). Subjects self-dosed once daily, beginning 1 day before undergoing cataract surgery with intraocular lens implantation (day -1) and again on the day of surgery (day 0) and for 14 days postoperatively. Follow-up was on days 1, 3, 8, and 15. The outcome measures included the percentage of subjects with zero-to-trace anterior chamber cells at each visit, as determined by the percentage of subjects with ≤5 anterior chamber cells, overall anterior chamber cell grades, and summed ocular inflammation score (SOIS) (combined anterior chamber cell and flare scores). RESULTS: The proportion of subjects with zero-to-trace anterior chamber cells was significantly higher in the bromfenac 0.07% group compared with the placebo group as early as day 3 (P=0.0007), continued at day 8 (P<0.0001), and through day 15 (P<0.0001). At day 15, 80.2% of subjects in the bromfenac 0.07% group achieved zero-to-trace anterior chamber cells compared with 47.2% of subjects who did so in the placebo group. The overall anterior chamber cell scores were significantly lower in the bromfenac 0.07% group compared with the placebo group at days 3, 8, and 15 (P<0.0001 at each visit). The SOIS were also significantly lower in the bromfenac group compared with the placebo group at days 3, 8, and 15 (P<0.0001 at each visit). CONCLUSION: Bromfenac ophthalmic solution 0.07%, dosed once daily was clinically effective in achieving zero-to-trace anterior chamber cell severity after cataract surgery and was superior to placebo in all anterior chamber cell severity and inflammation outcome measures.

Bromfenac ophthalmic solution 0.07% dosed once daily for cataract surgery: results of 2 randomized controlled trials.

PURPOSE: To evaluate the efficacy and ocular safety of bromfenac ophthalmic solution 0.07% (Prolensa) dosed once daily for the treatment of ocular inflammation and pain in subjects who underwent cataract surgery with posterior chamber intraocular lens implantation. DESIGN: Two phase 3, randomized, double-masked, placebo-controlled, multicenter clinical trials. PARTICIPANTS: Four hundred forty subjects (440 study eyes: 222 in the bromfenac group and 218 in the placebo group). METHODS: Two phase 3, prospective, randomized, double-masked, placebo-controlled clinical trials were conducted at 39 ophthalmology clinics in the United States. Subjects 18 years of age or older were randomized to receive either bromfenac 0.07% or placebo dosed once daily beginning 1 day before cataract surgery, on the day of surgery, and continuing for 14 days after surgery (for a total of 16 days). Subjects were evaluated on days 1, 3, 8, 15, and 22 after surgery. The primary efficacy end point was cleared ocular inflammation, as measured by the summed ocular inflammation score of zero (anterior chamber cell count = 0 and absence of flare) by day 15. Secondary end points included cleared ocular inflammation at day 15 and the number of subjects who were pain free at day 1. The data from the 2 clinical trials were integrated for analyses. MAIN OUTCOME MEASURES: Summed ocular inflammation score and ocular pain. RESULTS: A significantly higher proportion of subjects treated with bromfenac 0.07% achieved complete clearance of ocular inflammation by day 15 and at day 15 compared with placebo (P < 0.0001). A statistically significantly higher proportion of subjects in the bromfenac 0.07% group were pain free at all study visits compared with those in the placebo group (P < 0.0001). Fewer subjects in the bromfenac group (3.2%) discontinued investigational product early because of a lack of efficacy than in the placebo group (23.9%; P < 0.0001). The incidence of adverse events was significantly lower in the bromfenac 0.07% group compared with the placebo group (P = 0.0041). CONCLUSIONS: Bromfenac ophthalmic solution 0.07% dosed once daily was clinically safe and effective compared with placebo for the treatment of ocular inflammation and pain in subjects who had undergone cataract surgery and may be a beneficial addition to the current standard of care, which commonly includes ophthalmic antibiotics and corticosteroids.

Ulcerative keratitis in mycosis fungoides.

PURPOSE: To present a case of ulcerative keratitis and impending corneal perforation in a patient with mycosis fungoides (cutaneous T-cell lymphoma) that developed eyelid involvement. METHODS: Case report analysis. Cultures and biopsies of the right cornea, conjunctiva, and eyelids were obtained. Biopsy tissue was examined with histologic and immunohistologic stains. RESULTS: This patient with mycosis fungoides involving the eyelids developed corneal exposure and bacterial keratitis with impending corneal perforation. Lamellar keratoplasty and permanent tarsorrhaphy were performed to protect the globe from perforation. DISCUSSION: Mycosis fungoides involving the eyelids is capable of causing severe ocular tissue injury without direct infiltration of the malignant lymphocytes. Preventative medical and surgical measures must be taken to protect the globe.