Faculty Bibliography

PURPOSE/OBJECTIVE:To compare the safety and efficacy of IBI-10090 anterior chamber intracameral dexamethasone drug-delivery suspension (Dexycu) with those of prednisolone acetate 1.0% ophthalmic drops in treating inflammation after cataract surgery. SETTING/METHODS:Eleven centers in the United States. DESIGN/METHODS:Prospective randomized open-label multicenter trial. METHODS:Patients were randomized 2:1 to receive a 5 μL injection of 517 μg IBI-10090 in the anterior eye chamber or topical prednisolone 1.0% drops (1 drop 4 times daily for 3 weeks). The postoperative follow-up was 90 days. The primary outcome was safety, evaluated by the incidence and severity of adverse events. Exploratory measures were anterior chamber cell, anterior chamber flare, and anterior chamber cell-flare clearing. RESULTS:One hundred twenty-six IBI-10090 patients and 55 prednisolone patients were included in the safety analysis. Two serious adverse events unrelated to treatment were reported. The decrease in endothelial cell density was not significantly different between groups. The most common adverse events were increased intraocular pressure (11.1%), iritis (6.3%), and systemic (7.9% IBI-10090 group; 10.9% prednisolone group). By 8 days postoperatively, 51.6% of IBI-10090 eyes and 50.9% of prednisolone eyes had anterior chamber cell clearing; more than 98% of eyes had clearing at 90 days. The anterior chamber flare and anterior chamber cell-flare clearing results were similar. Of IBI-10090 patients, 68.7% strongly agreed that not having to use eyedrops was very convenient; 39.2% using prednisolone 1.0% strongly stated they would have preferred dropless therapy. CONCLUSION/CONCLUSIONS:The safety and efficacy of IBI-10090 and prednisolone 1.0% were similar, with IBI-10090 preferred over drops.

PURPOSE/OBJECTIVE:Characterize the safety and tolerability of lifitegrast ophthalmic solution 5.0% for the treatment of dry eye disease. METHODS:Pooled data from five randomized controlled trials were analyzed. Key inclusion criteria were adults with dry eye disease (Schirmer tear test score ⩾1 and ⩽10 mm, eye dryness score ⩾40 (visual analog scale 0-100), corneal staining score ⩾2.0 (0-4 scale)). Participants were randomized to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 84 or 360 days. Treatment-emergent adverse events and drop comfort scores were assessed. RESULTS:Overall, 2464 participants (lifitegrast, n = 1287; placebo, n = 1177) were included. Ocular treatment-emergent adverse events occurring in >5% in either group were instillation site irritation (lifitegrast, 15.2%; placebo, 2.8%), instillation site reaction (lifitegrast, 12.3%; placebo, 2.3%), and instillation site pain (lifitegrast, 9.8%; placebo, 2.1%); the most common (> 5%) nonocular treatment-emergent adverse event was dysgeusia (lifitegrast, 14.5%; placebo, 0.3%). The majority of treatment-emergent adverse events were mild to moderate in severity. Discontinuation due to treatment-emergent adverse events occurred in 7.0% (lifitegrast) versus 2.6% (placebo) of participants (ocular: 5.5% vs 1.5%; nonocular: 1.9% vs 1.1%). Drop comfort scores with lifitegrast improved within 3 min of instillation and the score at 3 min improved across visits (12-week trials (both eyes, day 84 vs 0): 2.0 vs 3.3; SONATA (day 360 vs 0): right eye, 1.2 vs 1.7; left eye, 1.2 vs 1.8). CONCLUSION/CONCLUSIONS:Lifitegrast ophthalmic solution 5.0% appeared to be safe and well tolerated for the treatment of dry eye disease. Drop comfort with lifitegrast improved within 3 min of instillation.

PURPOSE/OBJECTIVE:To evaluate a sequential treatment algorithm for visual and keratometric improvement in keratoconus patients after corneal crosslinking (CXL) followed by topography-guided photorefractive keratectomy (PRK). SETTING/METHODS:Ophthalmic Consultants of Long Island, Garden City, New York, USA. DESIGN/METHODS:Retrospective case series. METHODS:This study reviewed patients with keratoconus who had CXL followed by custom topography-guided PRK between April 2016 and December 2016. The following data were collected at baseline, the time of CXL, and 3 months and 6 months after PRK: uncorrected (UDVA) and corrected (CDVA) distance visual acuities, keratometric astigmatism, spherical equivalent, maximum and mean keratometry readings, and corneal thickness at the cone apex. Demographic data, age at time of CXL and PRK, and time elapsed between CXL and PRK were analyzed for significance and a correlation with visual and astigmatic outcomes. RESULTS:The study comprised 56 patients (62 eyes), 34 who had both topographic and refractive treatment and 28 patients who had treatment of topographic irregularities only. The mean age was 38.08 years ± 13.07 (SD) at CXL and 40.33 ± 13.44 years at topography-guided PRK. Six months after PRK, there was a significant improvement in UDVA and CDVA in the refractive group (20/60 and 20/30, respectively) versus the nonrefractive group (20/100 and 20/40, respectively). Ninety-three percent of eyes that had refractive treatment had 20/40 or better CDVA. There were no significant adverse events in any case. CONCLUSIONS:The data support the use of refractive treatment in addition to topographic treatment for visual improvement in patients with keratoconus having CXL and PRK.

Aim/UNASSIGNED:The purpose of this study was to compare visual outcomes, surgical time, and perioperative surgical complications after intracameral use of either phenylephrine/ketorolac (P/K) or epinephrine (Epi) during cataract surgery. Methods/UNASSIGNED:This was a single-center, retrospective case review of patients undergoing cataract surgery from August to November 2015. Of the 641 eyes of 389 patients who underwent cataract surgery, 260 eyes were administered phenylephrine 1.0%/ketorolac 0.3% and 381 eyes received Epi in the irrigation solution intraoperatively. All patients received a topical nonsteroidal anti-inflammatory drug regimen (bromfenac 0.07%, nepafenac 0.3%, or ketorolac 0.5%) for 3 days before surgery and topical tropicamide 1.0%, cyclopentolate 1.0%, and phenylephrine 2.5% on the day of surgery. Results/UNASSIGNED:Mean length of surgery (LOS) was 15.4±0.6 minutes. Although a positive correlation was noted between patient age and LOS (p<0.001), P/K was associated with a decrease in the LOS, when controlled for age quartiles. A statistically significant lower incidence of complications (1.1%) was observed with P/K use than Epi (4.5%; p=0.018). Among surgeons who used mydriatic-assist devices more frequently, P/K use was associated with a reduction in the use of these devices (p<0.001). When controlling for age quartile, patients of age groups 69-76 and 76-92 years who received P/K had significantly better uncorrected visual acuity at postoperative day 1 than those receiving Epi (p=0.003). Conclusion/UNASSIGNED:Intracameral use of phenylephrine 1.0%/ketorolac 0.3% during cataract surgery may be effective in maintaining mydriasis. It appears to be superior to intracameral Epi at reducing intraoperative and postoperative complications, need for pupillary dilating devices, and surgical time.

INTRODUCTION: Dry eye disease (DED) is a common ocular disorder that can have a substantial burden on quality of life and daily activities. Lifitegrast ophthalmic solution 5.0% is the first medication approved in the US for the treatment of the signs and symptoms of DED. The aim of this article is to summarize the preclinical and clinical data on lifitegrast and discuss how lifitegrast may fit into the current treatment landscape for DED. Areas covered: A literature search of published preclinical and clinical data was conducted to review the chemistry, pharmacodynamics, pharmacokinetics, and clinical efficacy/safety of lifitegrast. The impact that lifitegrast may have on DED treatment practices is also discussed. Expert opinion: The introduction of lifitegrast provides a potentially important additional option for eye care professionals treating DED. In clinical trials conducted in adults with DED, lifitegrast ophthalmic solution 5.0% improved both signs and symptoms of DED. Of note, in 2 phase 3 trials, symptom improvements were observed as early as 2 weeks, which may be explained by lifitegrast's unique mechanism of action of blocking a specific signaling pathway in inflammation. Future research should include evaluation of whether lifitegrast can be used in combination with other DED treatments.

PURPOSE/OBJECTIVE:To evaluate the study drug OMS302 (Omidria [phenylephrine and ketorolac injection 1.0%/0.3%]) compared with a balanced salt solution (vehicle), ketorolac, and phenylephrine on pupil diameter during cataract surgery and early postoperative ocular pain. SETTING/METHODS:Twenty-three centers in the United States. DESIGN/METHODS:Randomized clinical trial. METHODS:Patients were randomized (1:1:1:1) to receive vehicle, phenylephrine, ketorolac, or the study drug containing phenylephrine and ketorolac administered intracamerally during surgery. Intraoperative pupil diameter was determined each minute by video capture. Postoperative ocular pain was evaluated for up to 12 hours. RESULTS:The study evaluated 223 patients. The study drug was significantly better than the vehicle and ketorolac in maintaining mydriasis (least-squares mean differences 0.9 ± 0.1 [SEM] and 0.7 ± 0.1 for the study drug versus vehicle and ketorolac, respectively; P < .0001 each). Ocular pain assessed using the Visual Analog Scale was significantly reduced for the study drug compared with the vehicle or phenylephrine (least-squares mean difference -4.6 ± 2.2 and P = .042 and 5.9 ± 2.2 and P = .009, respectively). Significantly fewer patients treated with the study drug (3 [6.1%]) had an intraoperative pupil diameter smaller than 6.0 mm compared with those treated with the vehicle (25 [47.2%]; P < .0001), ketorolac (18 [34.6%]; P = .0004), or phenylephrine (11 [22.4%]; P = .0216). CONCLUSIONS:The study drug was safe and efficacious in maintaining mydriasis and reducing postoperative ocular pain. Both ketorolac and phenylephrine contributed to the therapeutic effects, with the combination showing superiority to either agent alone in maintaining an intraoperative pupil diameter of 6.0 mm or larger.

PURPOSE/OBJECTIVE:Dry eye disease is a multifactorial disease with numerous well-documented risk factors. However, to date, sleep position has not been associated with this condition. After observing patients in our practice, we believe that the sleep position in some cases may significantly affect dry eye and meibomian gland dysfunction (MGD). METHODS:This is a single-centered, cross-sectional, noninterventional, institutional review board-approved, single-masked, nonrandomized study of 100 patients whose complaints were related to dry eye disease and a control group of 25 age-matched asymptomatic patients. Two questionnaires were used: one to analyze patients' sleep habits and the other to assess patients' Ocular Surface Disease Index. Dry eye severity was graded based on the MGD stage, fluorescein corneal staining and lissamine green staining, Schirmer 1 testing, tear osmolarity levels, and clinical examination. RESULTS:A statistically significant difference was shown with back sleeping compared with left side sleeping using lissamine green staining (analysis of variance, P = 0.005). The Ocular Surface Disease Index score was also found to be elevated in patients who slept on their right or left side (36.4 and 34.1, respectively) as opposed to back sleepers (26.7) with P < 0.05. There was no statistically significant correlation found between the sleep position and degree of MGD. CONCLUSIONS:In addition to current treatment, patients who sleep on their side or face down might see a reduction in dry eye and MGD if they change their sleep pattern to the supine position.

PURPOSE/OBJECTIVE: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/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/CONCLUSIONS:The incidence of dry eye in patients scheduled to undergo cataract surgery in a real-world setting is higher than anticipated.

PURPOSE/OBJECTIVE:To evaluate the long-term intraocular pressure (IOP)-lowering effect and safety parameters following treatment with two trabecular micro-bypass stents and topical prostaglandin in phakic eyes with open-angle glaucoma (OAG) not controlled on two preoperative medications. METHODS:This prospective, single-arm, unmasked study enrolled 39 qualified phakic eyes with OAG not controlled on 2 medications, preoperative medicated IOP of 18-30 mmHg, and IOP following medication washout of 22-38 mmHg. Two trabecular micro-bypass stents were implanted as a standalone procedure, and travoprost was started on postoperative day 1. Evaluations included IOP, best-corrected visual acuity, medication use, fundus and slit-lamp examinations, visual field, cup:disc ratio, central corneal thickness, and ocular complications. Data through 18 months were summarized previously. Thirty-seven of the original 39 subjects have been followed for 3 years postoperatively; follow-up is continuing for 5 years. RESULTS:At 3 years postoperative, 97% of eyes had achieved an IOP reduction of ≥20% from baseline with a reduction of 1 medication. Eighty-six percent of eyes had IOP of ≤18 mmHg with a reduction of 1 medication. Mean medicated IOP decreased to 14.0±2.6 mmHg on 1 medication versus 22.4±2.3 mmHg on 2 medications preoperatively. The mean unmedicated IOP decreased to 17.7±1.7 mmHg at 37 months from 25.3±1.9 mmHg preoperatively. Long-term postoperative adverse events included cataract surgery in 3 eyes due to cataract progression, and trabeculectomy in 1 eye due to uncontrolled IOP of 23 mmHg. No intraoperative or device-related adverse events occurred. CONCLUSION/CONCLUSIONS:Significant and sustained reduction in IOP and medications with a favorable safety profile was shown through 3 years after implantation of 2 trabecular micro-bypass stents combined with postoperative travoprost in phakic OAG eyes uncontrolled on 2 preoperative medications. These findings demonstrate the long-term performance and safety of trabecular bypass stents in combination with topical prostaglandin for OAG patients.

PURPOSE/OBJECTIVE:To assess the effect of oral re-esterified omega-3 fatty acids on tear osmolarity, matrix metalloproteinase-9 (MMP-9), tear break-up time (TBUT), Ocular Surface Disease Index (OSDI), fluorescein corneal staining, Schirmer score, meibomian gland dysfunction (MGD) stage and omega-3 index in subjects with dry eyes and confirmed MGD. METHODS:This was a multicenter, prospective, interventional, placebo-controlled, double-masked study. Subjects were randomized to receive 4 softgels containing a total of 1680 mg of eicosapentaenoic acid/560 mg of docosahexaenoic acid or a control of 3136 mg of linoleic acid, daily for 12 weeks. Subjects were measured at baseline, week 6, and week 12 for tear osmolarity, TBUT, OSDI, fluorescein corneal staining, and Schirmer test with anesthesia. MMP-9 testing and omega-3 index were done at baseline and at 12 weeks. RESULTS:One hundred five subjects completed the study. They were randomized to omega-3 (n = 54) and control group (n = 51). Statistically significant reduction in tear osmolarity was observed in the omega-3 group versus control group at week 6 (-16.8 ± 2.6 vs. -9.0 ± 2.7 mOsm/L, P = 0.042) and week 12 (-19.4 ± 2.7 vs. -8.3 ± 2.8 mOsm/L, P = 0.004). At 12 weeks, a statistically significant increase in omega-3 index levels (P < 0.001) and TBUT (3.5 ± 0.5 s vs. 1.2 ± 0.5 s, P = 0.002) was also observed. Omega-3 group experienced a significant reduction in MMP-9 positivity versus control group (67.9% vs. 35.0%, P = 0.024) and OSDI scores decreased significantly in omega-3 (-17.0 ± 2.6) versus control group (-5.0 ± 2.7, P = 0.002). CONCLUSIONS:Oral consumption of re-esterified omega-3 fatty acids is associated with statistically significant improvement in tear osmolarity, omega-3 index levels, TBUT, MMP-9, and OSDI symptom scores.