The Effectiveness and Safety of a Novel Crosslinked Hyaluronate Canalicular Gel Occlusive Device for Dry Eye.

PURPOSE: Evaluate effectiveness and safety of a crosslinked hyaluronate (HA) canalicular filler (Lacrifill Canalicular Gel) compared to a commercially available hydrogel canalicular plug (Form Fit). SETTING: 5 sites in United States. DESIGN: Prospective, multicenter, controlled, double-masked, randomized 2:1 (filler:plug). METHODS: Adults (≥22 years) with Schirmer test (with anesthesia) ≤10 mm/5 minutes, presence of corneal staining, ocular surface disease index (OSDI) of ≥23 with ≤3 responses of "not applicable," patent lacrimal drainage system, and bilateral best-corrected distance visual acuity of 20/40 or better. Filler or plugs were instilled bilaterally in the inferior canaliculi. Primary effectiveness endpoint was non-inferiority of the mean within subject change from baseline to Month 3 in Schirmer score for patients receiving filler compared to plugs. The key secondary effectiveness endpoint was non-inferiority of the proportion of patients with filler achieving improvement from baseline to Month 3 in OSDI by a minimal clinically important difference (MCID). Additional endpoints included the mean change from baseline to 3 and 6 months in tear meniscus height, OSDI, corneal staining, tear break-up time, and safety. RESULTS: 157 patients were randomized; 99 patients with crosslinked HA filler and 52 patients with hydrogel plugs completed the study. Filler was non-inferior to plugs in the mean Schirmer score change from baseline and in the proportion of patients achieving a clinically important improvement in OSDI. CONCLUSIONS: Crosslinked HA filler is a safe, well-tolerated, and effective method to treat dry eye. Clinically and statistically significant improvements in signs and symptoms of dry eye were sustained through 6 months.

Efficacy and Safety of CSF-1 (0.4% Pilocarpine Hydrochloride) in Presbyopia: Pooled Results of the NEAR Phase 3 Randomized, Clinical Trials.

PURPOSE: This study was undertaken to evaluate the safety and efficacy of CSF-1 (0.4% pilocarpine hydrochloride ophthalmic solution) for use in individuals with presbyopia. METHODS: Two Phase 3 multicenter, randomized, double-masked, vehicle-controlled, parallel-group clinical trials were conducted in 35 private ophthalmology clinics in the United States from October 2020 to February 2022. Key inclusion criteria were the following: (1) age 45-64 years, (2) distance-corrected near visual acuity (DCNVA) at 40 cm ≥0.40 and ≤0.90 logarithm of the minimum angle of resolution (logMAR, approximately 20/50-20/160 Snellen) in at least 1 eye, (3) manifest refraction (MR) between -4.50 and +2.00 diopter (D) sphere in each eye with ≤2.00D difference between eyes, (4) <2.00D of cylinder MR in each eye, (5) ≤0.04 logMAR (20/20-2 or better) corrected distance visual acuity (CDVA) at 4 m in each eye. Key exclusion criteria were the following: (1) >0.14 logMAR (7 letters) improvement in post-vehicle treatment in monocular DCNVA in either eye at visit 1, (2) introcular pressure (IOP) <9 or >22 mm Hg, (3) average dark-adapted pupillometry <3.5 mm in either eye, (4) prior refractive surgery or intraocular lens (IOL) implantation. Participants applied CSF-1 or vehicle twice per day for 2 weeks. Efficacy and safety assessments were performed at several times on days 1, 8, and 15. Response was defined as ≥3-line gain in DCNVA without loss of ≥1-line in CDVA in the study eye under mesopic room lighting conditions. The primary efficacy endpoint was measured 1 hour post-dose 1 on day 8. Key secondary endpoints were 2 hours post-dose 1, and 1 and 2 hours post-dose 2, also on day 8. Safety endpoints were ocular and non-ocular treatment-related adverse events (TRAE), conjunctival redness, drop comfort, slit-lamp biomicroscopy, intraocular pressure, indirect fundoscopy, and CDVA at 4 m. FINDINGS: Six hundred thirteen participants were randomized to CSF-1 (n = 309) or vehicle (n = 304). Participants were predominantly White (80.8%) and female (62.0%), with mean age (standard deviation) of 54.7 (4.8). CSF-1 met the primary and key secondary endpoints. At the primary endpoint, 40.1% of the CSF-1 group achieved response versus 19.1% of the vehicle group (P < 0.0001). The percentage of responders was significantly greater in CSF-1 compared with vehicle at all tested times. Changes from baseline in all safety endpoints were comparable between groups. Most adverse events (AEs) were mild and transient. Neither serious nor severe AEs were reported with CSF-1. IMPLICATIONS: CSF-1, a low-dose pilocarpine ophthalmic solution, demonstrated superiority to vehicle in improving near vision in individuals with presbyopia without compromising distance vision. CSF-1 demonstrated a favorable safety profile. CLINICALTRIALS: gov identifier: NCT04599933 (NEAR-1), NCT04599972 (NEAR-2).

0.2% Betamethasone Sodium Phosphate: A Multicenter, Randomized, Double-Masked Study to Compare Its Ocular Safety, Tolerability, and Efficacy to Vehicle in Cataract Surgery Subjects.

Purpose: To compare the preservative-free corticosteroid 0.2% betamethasone sodium phosphate BID (SURF-201) to vehicle BID in patients undergoing routine cataract surgery. Methods: Phase 2, multicenter, randomized (1:1 ratio), double-masked, vehicle-controlled, parallel-group study in patients scheduled for uncomplicated cataract surgery without the aid of a femtosecond laser. Subjects instilled topical medications for 16 days beginning the day before cataract surgery (Day -1), 1 dose administered at least 1 hour prior to cataract surgery (on Day 0) and 1 dose on the evening after cataract surgery, and then 2 doses administered each day through Day 15; patients were re-evaluated on Days 22 and 32 to ensure no rebound inflammation. Primary outcome was the difference in the proportion of subjects with anterior chamber cell (ACC) grade 0 between the two groups at Day 15. Secondary outcomes included pain scores and overall safety. Results: There was a statistically significant difference (P=0.004) in the proportion of subjects in the SURF-201 treatment group with an ACC grade of 0 at Day 15 (n=22/39 [56.4%]) compared to subjects in the vehicle treatment group (n=9/43 [20.9%]). There was no statistically significant difference (P=0.528) in the proportion of subjects in the SURF-201 treatment group who had a visual analog scale pain score of 0 at Day 15 (n=35/38 [89.7%]) compared to subjects in the vehicle group (n=33/40 [82.5%]). A slightly higher incidence of adverse events occurred in subjects in the SURF-201 treatment group (n=27/40 [67.5%]) compared to the vehicle treatment group (n=23/43 [53.5%]). Conclusion: SURF-201 is an effective topical, preservative-free corticosteroid when dosed BID for the treatment of postoperative inflammation and prevention of pain in a post-cataract population.

Clinical diagnosis and management of Demodex blepharitis: the Demodex Expert Panel on Treatment and Eyelid Health (DEPTH).

BACKGROUND: Twelve ocular surface disease experts convened to achieve consensus about Demodex blepharitis (DB) using a modified Delphi panel process. METHODS: Online surveys were administered using scaled, open-ended, true/false, and multiple-choice questions. Consensus for questions using a 1 to 9 Likert scale was predefined as median scores of 7-9 and 1-3. For other question types, consensus was achieved when 8 of 12 panellists agreed. Questions were randomized, and results of each survey informed the following survey. RESULTS: Twelve practitioners comprised the Demodex Expert Panel on Treatment and Eyelid Health (DEPTH). Following 3 surveys, experts agreed that DB is chronic (n = 11) and recurrent (n = 12) and is often misdiagnosed. Consensus was achieved regarding inflammation driving symptoms (median = 7; range 7-9), collarettes as the most common sign (n = 10) and pathognomonic for DB (median = 9; range 8-9), and itching as the most common symptom (n = 12). Panellists agreed that DB may be diagnosed based on collarettes, mites, and/or patient symptoms (n = 10) and felt that patients unresponsive to typical therapies should be evaluated for DB (n = 12). Consensus about the most effective currently available OTC treatment was not reached. CONCLUSIONS: The Delphi methodology proved effective in establishing consensus about DB, including signs, symptoms, and diagnosis. Consensus was not reached about the best treatment or how to grade severity. With increased awareness, eyecare practitioners can offer DB patients better clinical outcomes. A follow-up Delphi panel is planned to obtain further consensus surrounding DB treatment.

Delphi Panel Consensus Regarding Current Clinical Practice Management Options for Demodex blepharitis.

Purpose: To obtain consensus on Demodex blepharitis (DB) treatment using a modified Delphi panel process. Methods: Literature search identified gaps in knowledge surrounding treatment of DB. Twelve ocular surface disease experts comprised the Demodex Expert Panel on Treatment and Eyelid Health (DEPTH). They completed a live roundtable discussion in addition to 3 surveys consisting of scaled, open-ended, true/false, and multiple-choice questions pertaining to the treatment of DB. Consensus for scaled questions using a 1 to 9 Likert scale was predefined as median scores of 7-9 and 1-3. For other question types, consensus was achieved when 8 of 12 panelists agreed. Results: The experts agreed that an effective therapeutic agent for treatment of DB would likely decrease the necessity of mechanical intervention, such as lid scrubs or blepharoexfoliation (Median = 8.5; Range 2-9). When treating DB, panelists believed that collarettes serve as a surrogate for mites, and that eliminating or reducing collarettes should be the main clinical goal of treatment (Median = 8; Range 7-9). The panelists would treat patients with at least 10 collarettes, regardless of other signs or symptoms and agreed that DB can be cured, but there is always the possibility for a reinfestation (n = 12). There was also consensus that collarettes, and therefore mites, are the primary treatment target and the way by which clinicians can monitor patient response to therapy (Median = 8; Range 7-9). Conclusion: Expert panelists achieved consensus on key facets of DB treatment. Specifically, there was consensus that collarettes are pathognomonic for DB, that DB patients with >10 collarettes should be treated even in the absence of symptoms, and that treatment efficacy can be tracked by collarette resolution. By increasing awareness about DB, understanding the goals of and monitoring treatment efficacy, patients will receive better care and, ultimately, better clinical outcomes.

Direct selective laser trabeculoplasty in open angle glaucoma study design: a multicentre, randomised, controlled, investigator-masked trial (GLAUrious).

INTRODUCTION: Laser trabeculoplasty is an effective and widely used treatment for glaucoma. A new laser technology, the Eagle direct selective laser trabeculoplasty (DSLT) device, may provide automated, fast, simple, safe and effective laser treatment for glaucoma in a broader range of clinical settings. This trial aims to test the hypothesis that translimbal DSLT is effective and not inferior to selective laser trabeculoplasty (SLT) in reducing intraocular pressure (IOP) in open angle glaucoma (OAG). METHODS AND ANALYSIS: This is a multicentre, randomised, controlled, investigator-masked study. The primary efficacy outcome is intergroup difference in mean change from baseline IOP measured at 6 months. Secondary outcomes include mean percentage reduction in IOP at 3, 6 and 12 months; proportion of participants with at least 20% reduction in IOP from baseline at 6 months; change in ocular hypotensive medications at 12 months and evaluation of safety. Participants were aged >= 40 years with OAG, including exfoliative or pigmentary glaucoma, or ocular hypertension with untreated or washed out IOP 22-35 mm Hg. TREATMENTS: DSLT: 120 shots, 3 ns, 400 µm spot size, energy 1.4-1.8 mJ delivered at the limbus over 2 s. SLT: approximately 100 shots, 3 ns, 400 µm spot size administered 360 degrees at the limbus using any gonioscopy lens, energy 0.3-2.6 mJ. A sample size of 164 is sufficient to detect a non-inferiority margin of 1.95 mm Hg for change from baseline IOP. CLINICAL TRIAL REGISTRATION NUMBER: NCT03750201, ISRCTN14033075.

Phase 2, Randomized, Open-Label Parallel-Group Study of Two Dosing Regimens of Netarsudil for the Treatment of Corneal Edema Due to Fuchs Corneal Dystrophy.

Background: This phase 2 study evaluated the therapeutic potential of netarsudil to reduce corneal edema and to improve vision in patients with Fuchs corneal dystrophy (FCD). Methods: Patients (N = 40) with baseline central corneal thickness (CCT) of ≥600 µm and best-corrected visual acuity (BCVA) of 70-20 letters (20/40-20/400 Snellen equivalent) were randomized 1:1 to receive netarsudil once a day (QD) or twice a day (BID) for 8 weeks. Primary endpoint was mean CCT change from baseline at week 4. Results: Netarsudil QD and BID significantly reduced CCT at week 4 [mean change (standard error of mean), 28.4 (7.99) µm, P = 0.0021; and 20.1 (8.75) µm, P = 0.0335, respectively]. Five (12.5%) patients achieved complete resolution of corneal edema at week 4. BCVA improved by 3.2 (2.76) letters with QD and 1.5 (2.84) letters with BID, and 10 (25%) patients [5 with QD (P = 0.0078) and 5 with BID (P = 0.0096)] gained ≥10 letters at week 4. Improvements in CCT and vision were observed at week 2 and persisted at week 8, without significant differences between the 2 doses at any time point. Netarsudil QD significantly improved visual acuity and glare factor scores on the Visual Function and Corneal Health Status (V-FUCHS) questionnaire at weeks 4 and 8 (mean change, -0.4 to -0.3; P ≤ 0.0200). Netarsudil was well tolerated. Reticular edema developed in one (2.5%) patient with BID, which resolved with treatment discontinuation. Conclusions: Netarsudil QD led to significant reductions in corneal edema as well as improvements in vision and patient-reported symptoms of glare and visual impairment in patients with FCD. Clinical Trial Registration Number: NCT04498169.

Energy Dose-Response in Selective Laser Trabeculoplasty: A Review.

PRCIS: A literature review of selective laser trabeculoplasty (SLT) energy dose-response found no definitive relationship between intraocular pressure (IOP) reduction with respect to total or pulse energy, race, pigmentation, or application pattern. PURPOSE: SLT is a safe and effective treatment for lowering IOP. Although evidence is mounting for the advantage of its use as a first-line treatment for IOP reduction, the SLT procedures in use vary widely. The purpose of this literature review was to investigate whether there were any relationships between SLT energy and efficacy for lowering IOP in the published literature. METHODS: A literature review was undertaken that included studies in which energy levels required for successful SLT treatment were investigated: in general, with respect to angle pigmentation, race or ethnicity, and treatment arc extent. RESULTS: There was no indication that higher (or lower) energy used in the treatment leads to greater (or less) IOP reduction. Similar results were obtained regarding the level of trabecular meshwork pigmentation. Race was not found to be associated with altered dose response in SLT. There were indications that treating the full 360 degrees, as opposed to smaller arcs, could be beneficial for more IOP reduction. IOP reduction from SLT was found to be similar to that provided by topical medications. CONCLUSIONS: The optimal energy level of SLT needed for IOP reduction has not yet been definitively established, with all reported pulse energies resulting in similar IOP reduction. Furthermore, similar lack of conclusive findings exists regarding optimal SLT energy dosage for use in different races and degrees of trabecular meshwork pigmentation. This parameter and each of the abovementioned factors requires further research.

Corneal cross-linking versus conventional management for keratoconus: a lifetime economic model.

AIMS: To assess the cost-effectiveness of corneal collagen cross-linking (CXL) versus no CXL for keratoconus in the United States (US). METHODS: A discrete-event microsimulation was developed to assess the cost-effectiveness of corneal cross-linking (CXL, Photrexa + KXL combination product) versus no CXL for patients with keratoconus. The lifetime model was conducted from a US payor perspective. The source for CXL efficacy and safety data was a 12-month randomized, open-label, sham-controlled, multi-center, pivotal trial comparing CXL versus no CXL. Other inputs were sourced from the literature. The primary outcome was the incremental cost per quality-adjusted life year gained. Costs (2019 USD) and effects were discounted 3% annually. The impacts of underlying uncertainty were evaluated by scenario, univariate, and probabilistic analyses. RESULTS: Starting at a mean baseline age of 31 years and considering a mixed population consisting of 80% slow-progressors and 20% fast-progressors, the CXL group was 25.9% less likely to undergo penetrating keratoplasty (PK) and spent 27.9 fewer years in advanced disease stages. CXL was dominant with lower total direct medical costs (-$8,677; $30,994 versus $39,671) and more QALYs (1.88; 21.80 versus 19.93) compared to no CXL. Considering the impact of reduced productivity loss in an exploratory scenario, CXL was associated with a lifetime cost-savings of $43,759 per patient. CXL was cost-effective within 2 years and cost-saving within 4.5 years. LIMITATIONS: Limitations include those that are common to similar pharmacoeconomic models that rely on disparate sources for inputs and extrapolation on short-term outcomes to a long-term analytical horizon. CONCLUSIONS: Keratoconus is a progressive and life-altering disease with substantial clinical, economic, and humanistic consequences. The economic value of cross-linking is maximized when applied earlier in the disease process and/or younger age, and extends to improved work productivity, out-of-pocket costs, and quality of life.

Evaluation of the IOP-Lowering Effect of a Multi-Pressure Dial at Different Negative Pressure Settings.

Purpose: To evaluate the intraocular pressure (IOP)-lowering effect of a multi-pressure dial (MPD) at targeted negative pressure settings. Methods: Prospective, intrasubject controlled study of 65 healthy subjects randomized to receive no negative pressure for 60 minutes or negative pressure application at designated levels of 25%, 50%, and 75% of baseline IOP for 20 minutes each. The main outcome measure was mean IOP with application of negative pressure. Results: In the study eye group, from a baseline IOP of 15.8 ± 3.6 mm Hg, the mean IOP was 13.5 ± 3.4, 11.5 ± 3.1, and 10.2 ± 2.7 mm Hg with negative pressure settings of 25%, 50% and 75%, respectively. In the control eye group, from a baseline IOP of 15.5 ± 3.0 mm Hg, the mean IOP values at the same time points, without negative pressure, were 15.6 ± 3.0, 15.5 ± 2.5 and 15.3 ± 2.4 mm Hg. The difference between the mean IOPs of the two groups was significantly different at all negative pressure settings (P < 0.001) in comparison with baseline. There was one minor adverse event, a corneal abrasion, that was unrelated to device wear. Conclusions: Negative pressure application to the periocular space with a multi-pressure dial can produce titratable IOP reduction while the device is worn with active negative pressure. To our knowledge, this technology represents the first nonpharmacologic, nonlaser, nonsurgical method for IOP reduction. Translational Relevance: This represents the first study demonstrating the IOP-lowering ability of the multi-pressure dial, a device that uses a novel IOP-lowering strategy by delivering negative pressure to the periocular region.

Baseline Visual Acuity at Wet AMD Diagnosis Predicts Long-Term Vision Outcomes: An Analysis of the IRIS Registry.

BACKGROUND AND OBJECTIVE: Clinical trials in neovascular age-related macular degeneration (nAMD) demonstrate that high visual acuity (VA) can be maintained, and low VA can be improved with anti-vascular endothelial growth factor (VEGF) treatment. Few real-world data investigating the relationship between baseline VA and long-term outcomes exist. This study compares VA at diagnosis and after treatment using data from a large patient registry. PATIENTS AND METHODS: Retrospective study of IRIS Registry patients diagnosed with nAMD in one or both eyes between January 2013 and June 2017. Patients received at least two anti-VEGF injections in the study eye(s) less than 45 days apart during the study period. Primary outcomes were the percentage of eyes with 20/40 VA or better at diagnosis and association of VA at diagnosis with longer-term visual outcomes. RESULTS: The study included 162,902 eyes. Among all included eyes, 34.3% presented with 20/40 VA or better at diagnosis. Patients with 20/40 vision or better at baseline maintained a mean VA of 20/40 or better for 2 years after treatment initiation. CONCLUSIONS: Baseline VA at nAMD diagnosis predicts long-term VA outcomes. Early diagnosis before VA is adversely affected is a key factor in preserving vision in patients with nAMD. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:633-639.].

Overnight Safety Evaluation of a Multi-Pressure Dial in Eyes with Glaucoma: Prospective, Open-Label, Randomized Study.

PURPOSE: To investigate the safety and tolerability of the multi-pressure dial (MPD) worn overnight for seven consecutive days. DESIGN: Prospective, open-label, randomized, single-site study. SUBJECTS: Twenty eyes of 10 subjects with open-angle glaucoma were fitted with an MPD and randomized to negative pressure application of -10 mmHg in one eye (study eye) worn overnight for 7 consecutive days. METHODS: Safety measures included best-corrected visual acuity (BCVA), intraocular pressure (IOP) changes from baseline during and after negative pressure application, slit lamp and dilated fundus exam findings, and rate of adverse events. Subjective assessments were completed daily by the subjects during the 7-day study period and immediately following the study period. RESULTS: Prior to the 7-day testing period, application of 10 mmHg negative pressure reduced mean IOP from 18.2 ± 3.8 mmHg to 14.0 ± 2.1 mmHg (p<0.01), a 22% reduction. After 7 days of consecutive nightly wear, repeat IOP measurements with the application of negative pressure showed a decrease in mean IOP from 16.9 ± 4.3 mmHg to 13.5 ± 3.7 mmHg. The observed IOP reduction was in addition to the subjects' current treatment regimen. There were no statistically significant changes in IOP, BCVA from baseline following the 7-day period of nightly wear with the application of negative pressure. The patient-reported outcomes were favorable. CONCLUSION: The MPD can safely and comfortably be worn overnight. The decrease in IOP of >20% in addition to current therapy is both clinically and statistically significant. The MPD shows promise as a potential new treatment option for nocturnal IOP control.

Four-Year Outcomes of Two Second-Generation Trabecular Micro-Bypass Stents in Patients with Open-Angle Glaucoma on One Medication.

INTRODUCTION: This study evaluated long-term reductions in intraocular pressure (IOP) and medication following implantation of 2 second-generation trabecular micro-bypass stents (iStent inject®) in eyes with open-angle glaucoma (OAG) not controlled on 1 preoperative medication. MATERIAL AND METHODS: In this prospective interventional multi-surgeon study, standalone implantation of 2 iStent inject stents was performed in 57 eyes of 57 subjects with OAG, preoperative IOP of 18-30 mmHg on 1 medication, and preoperative post-washout IOP of 22-38 mmHg. The main outcome measures included the proportions of eyes achieving medication-free IOP ≤18 mmHg, IOP ≤15 mmHg, or ≥20% IOP reduction versus preoperative unmedicated IOP. Assessments included IOP, medications, visual acuity, visual field, pachymetry, complications, and interventions. Subjects were followed for 48 months with follow-up continuing in all eyes. RESULTS: At Month 48 (n=57), 95% of eyes achieved an IOP reduction of ≥20% without medication versus preoperative washout IOP; and although they had eliminated medication, 81% of eyes still had an IOP reduction of ≥20% versus preoperative IOP on 1 medication. Mean 48-month unmedicated IOP decreased by 46% to 13.2±1.6 mmHg vs 24.4±1.3 mmHg preoperatively (p<0.0001), with 95% of medication-free eyes having IOP ≤18mmHg and 82% having IOP ≤15mmHg. Over the course of follow-up, 3 eyes had medication added and 1 eye underwent a secondary glaucoma surgery, and safety parameters were favorable. DISCUSSION: Standalone iStent inject implantation in OAG patients on 1 preoperative medication resulted in average IOP reduction to ≤15 mmHg with the elimination of medication and favorable safety through 48 months. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02868190.

Effect of Graft Attachment Status and Intraocular Pressure on Descemet Stripping Automated Endothelial Keratoplasty Outcomes in the Cornea Preservation Time Study.

PURPOSE: To examine the association of donor, recipient, and operative factors on graft dislocation after Descemet stripping automated endothelial keratoplasty (DSAEK) in the Cornea Preservation Time Study (CPTS) as well as the effects of graft dislocation and elevated IOP on graft success and endothelial cell density (ECD) 3 years postoperatively. DESIGN: Cohort study within a multi-center, double-masked, randomized clinical trial. METHODS: 1090 individuals (1330 study eyes), median age 70 years, undergoing DSAEK for Fuchs endothelial corneal dystrophy (94% of eyes) or pseudophakic or aphakic corneal edema (6% of eyes). Recipient eyes receiving donor corneal tissue randomized by preservation time (PT) of 0-7 days (N = 675) or 8-14 days (N = 655) were monitored for early or late graft failure through 3 years. Donor, recipient, operative, and postoperative parameters were recorded including graft dislocation (GD), partial detachment, and pre- and post-operative IOP. Pre- and postoperative central donor ECD were determined by a central image analysis reading center. Proportional hazards, mixed effects, and logistic regression models estimated risk ratios and (99% confidence intervals). RESULTS: Three independent predictive factors for GD were identified: a history of donor diabetes (odds ratio [OR]: 2.29 [1.30, 4.02]), increased pre-lamellar dissection central corneal thickness (OR: 1.13 [1.01, 1.27] per 25µ increase), and operative complications (OR: 2.97 [1.24, 7.11]). Among 104 (8%) eyes with GD, 30 (28.9%) developed primary donor or early failure and 5 (4.8%) developed late failure vs. 15 (1.2%; P < .001) and 29 (2.4%; P = .04), respectively, of 1226 eyes without GD. 24 (2%) of 1330 study eyes had early acutely elevated postoperative IOP that was associated with a higher risk of graft failure through 3 years (hazard ratio: 3.42 [1.01, 11.53]), but not with a lower mean 3-year ECD (mean difference 61 (-479, 601) cells/mm2, P = .77). History of elevated postoperative IOP beyond 1 month was not significantly associated with 3-year graft success or ECD. CONCLUSIONS: Donor diabetes, increased donor corneal thickness, and intraoperative complications were associated with an increased risk of GD. Early acutely elevated postoperative IOP and GD significantly increased the risk for graft failure following DSAEK.

Believable Statements of Uncertainty and Believable Science.

Nearly fifty years ago, two landmark papers appeared that should have cured the problem of ambiguous uncertainty statements in published data. Eisenhart's paper in Science called for statistically meaningful numbers, and Currie's Analytical Chemistry paper revealed the wide range in common definitions of detection limit. Confusion and worse can result when uncertainties are misinterpreted or ignored. The recent stories of cold fusion, variable radioactive decay, and piezonuclear reactions provide cautionary examples in which prior probability has been neglected. We show examples from our laboratory and others to illustrate the fact that uncertainty depends on both statistical and scientific judgment.

Dropless Cataract Surgery: An Overview.

Risk reduction and the attainment of good outcomes in contemporary cataract surgery depend in part on patient compliance with a postoperative regimen of topical eye drops. Topical drops are expensive and challenging to instill properly for patients. The consequences of noncompliance or poor compliance can be significant for the patient (in the case of a complication) and for society (in the case of development of antibiotic resistance). For all of these reasons, new approaches that reduce the need for topical therapy are beginning to emerge, including intracameral injection, sustained or slow-release drug delivery mechanisms, and the recently introduced "Dropless cataract surgery," which involves intravitreal injection of single-use, compounded combination of antibiotics and corticosteroids. This paper is a review of the rationale for reducing topical therapy in cataract surgery prophylaxis, and what is known to date about the efficacy and safety of the dropless approach.

A second-generation low-background gamma-ray spectrometer.

For the ultimate sensitivity in trace radiochemical analysis, the radiation detector must have high efficiency and low background. A low-background gamma-ray spectrometer in regular use at NIST for over twenty years is being supplemented by a new system, improved in several ways. The new detector is much larger, a shield of iron reduces cosmic neutron background compared with lead, large plastic scintillators reduce the muon continuum background, and a digital data acquisition system gives new opportunities for optimization.

A randomized double-masked study to compare the ocular safety, tolerability, and efficacy of bromfenac 0.075% compared with vehicle in cataract surgery subjects.

PURPOSE: The aim of this study was to evaluate the safety, tolerability, and efficacy of a low-dose version of bromfenac 0.075% in DuraSite® (bromfenac 0.075%) compared with DuraSite® vehicle (vehicle) alone for the treatment of postoperative inflammation and ocular pain after cataract surgery. METHODS: A multicenter, double-masked, vehicle-controlled, parallel-group clinical trial of 240 subjects randomized in a 2:1 ratio to bromfenac 0.075% or vehicle was conducted. Subjects were dosed BID beginning 1 day before the cataract surgery, the day of surgery, and 14 days after surgery. A slit lamp biomicroscopy examination was performed to evaluate the signs of inflammation, including anterior chamber cells (ACC) and anterior chamber flare (ACF). The primary efficacy variable was the proportion of subjects with an ACC grade of 0 at Day 15. Secondary efficacy endpoints included the proportion of subjects who achieved a pain score of 0 at each postsurgical visual analog scale (VAS) assessment and the proportion of subjects with an ACF grade of 0 at Day 15. RESULTS: At Day 15, proportionally more subjects in the bromfenac 0.075% group than in the vehicle group had an ACC grade of 0 (57.1% vs 18.8%, respectively; P<0.001). At each of the postsurgical time points (Days 1, 8, 15, and 29), proportionally more bromfenac 0.075%-treated subjects (76.8%, 90.5%, 92.9%, and 85.1%, respectively) had no pain (a VAS score of 0) compared with the vehicle-treated subjects (48.2%, 38.8%, 42.4%, and 47.1%, respectively), and at each time point, these differences in proportions were statistically significant (P<0.001). More subjects in the bromfenac 0.075% group had complete ACF resolution (151/167; 90.4%) compared to those in the vehicle group (54/85; 63.5%). There were no new safety signals reported. CONCLUSION: Bromfenac 0.075% in DuraSite is safe, well tolerated, and effective at reducing inflammation and preventing pain associated with cataract surgery.

Outcomes Following Implantation of Two Second-Generation Trabecular Micro-Bypass Stents in Patients with Open-Angle Glaucoma on One Medication: 18-Month Follow-Up.

INTRODUCTION: The study objective was to evaluate the intraocular pressure (IOP) and medication-lowering effect of 2 second-generation trabecular micro-bypass stents in eyes with open-angle glaucoma (OAG) on one preoperative medication. METHODS: Fifty-seven qualified phakic eyes with OAG on 1 medication, preoperative medicated IOP of 18-30 mmHg, and preoperative unmedicated (post-washout) IOP of 22-38 mmHg underwent implantation of 2 second-generation trabecular micro-bypass stents in a standalone procedure. Evaluations included IOP, best-corrected visual acuity, medication use, fundus and slit lamp examinations, visual field, cup to disc ratio, pachymetry, and complications and interventions. Subjects have been followed for 18 months, and follow-up is ongoing. RESULTS: At Month 12 postoperative, 100% of eyes had achieved an IOP reduction ≥20% (100% had IOP ≤18 mmHg and 67% had IOP ≤15 mmHg) without medication versus preoperative unmedicated IOP, and 75% had IOP reduction ≥20% without medication versus preoperative medicated IOP. The Month 12 mean unmedicated IOP had decreased by 42%, to 14.2 ± 1.9 mmHg vs 24.4 ± 1.3 mmHg preoperatively, and this reduction was maintained through 18 months (14.4 ± 2.1 mmHg). A high safety profile was observed. CONCLUSION: In this prospective, open-label, single-arm study, the standalone implantation of two second-generation trabecular micro-bypass stents in OAG patients on 1 preoperative medication resulted in IOP reduction to ≤15 mmHg and elimination of medication through 18 months, with favorable safety. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02868190. FUNDING: Glaukos Corporation, San Clemente, CA.