Real-World Study of the Effectiveness and Safety of Intracameral Bimatoprost Implant in a Clinical Setting in the United States.

Purpose: A sustained-release, biodegradable, intracameral 10-µg bimatoprost implant (Durysta) is approved for single administration per eye to lower intraocular pressure (IOP) in open-angle glaucoma (OAG) and ocular hypertension (OHT). The purpose of this study was to evaluate the IOP-lowering effectiveness and safety of a single implant administration per eye in patients with OAG or OHT in a real-world clinical setting. Methods: This was a retrospective, single-site study involving 105 consecutive adult patients with OAG or OHT treated with the bimatoprost implant in 1 or both eyes in routine clinical practice. Available medical records of the patients for 12 months or longer after the initial implant administration were reviewed, and data including IOP, IOP-lowering medication and procedure use, and safety outcomes were collected and analyzed. The analysis used ranges of follow-up because of the real-world setting. Results: The study included 197 eyes (85.3% diagnosed with OAG, 94.9% pseudophakic, and 83.8% with angle grade 4). IOP reduction was observed through 1 year after the bimatoprost implant administration. Mean IOP was 16.6 mmHg at baseline and 13.3 mmHg at 11-13 months, with the mean number of topical IOP-lowering medications used reduced from 1.4 at baseline to 0.2 at 11-13 months. IOP and IOP-lowering medication use were similarly reduced in eyes treated with both selective laser trabeculoplasty (SLT) and bimatoprost implant (including 66 eyes with their last SLT before implant administration and 28 eyes with their last SLT after implant administration). There were no cases of treatment-emergent corneal edema after bimatoprost implant administration, and no eye required implant removal. Conclusion: A single bimatoprost implant administration safely and effectively reduced IOP for up to 1 year and decreased the need for topical IOP-lowering medications in eyes with OAG or OHT with or without previous or subsequent SLT.

Phase 3, Randomized Study Comparing Intracameral Bimatoprost Implant 15 µg and Selective Laser Trabeculectomy in Patients with Open-Angle Glaucoma or Ocular Hypertension.

Purpose: We evaluate the safety and intraocular pressure (IOP)-lowering effect of 15-µg bimatoprost implant (higher dose than the currently approved product) compared with selective laser trabeculoplasty (SLT) in patients with open-angle glaucoma or ocular hypertension. Methods: Randomized, phase 3, 12-month, multicenter, paired-eye, patient- and efficacy evaluator-masked noninferiority study. Patients with inadequate IOP control were randomized to receive 360° SLT (day 1) or up to 3 administrations of 15-µg bimatoprost implant (day 4, weeks 16 and 32) in the primary eye and the alternative treatment in the contralateral eye. The primary endpoint was IOP change from baseline at weeks 4, 12, and 24. Results: At weeks 4, 12, and 24, mean IOP change from baseline ranged from -7.01 to -6.65 mm Hg in implant-treated eyes (N=138) and -6.45 to -6.26 mm Hg in SLT-treated eyes (N=138). Differences in IOP change from baseline ranged from -0.70 to -0.25 mm Hg favoring implant; the upper limit of the 95% confidence interval of the difference (implant minus SLT) was <1.0 mm Hg at all 3 visits. The probability of requiring no additional (rescue) IOP-lowering treatment in implant-treated versus SLT-treated eyes was 93.6% versus 86.5% at day 180 and 74.6% versus 77.1% at day 360. Corneal endothelial cell loss was more common in implant-treated eyes and typically occurred after repeated implant administration. Conclusion: Bimatoprost implant 15 µg met prespecified criteria for statistical and clinical noninferiority to SLT in lowering IOP, and after 1, 2, or 3 administrations, demonstrated a duration of IOP lowering similar to SLT. Bimatoprost implant 15 µg was associated with corneal adverse events in some patients, especially after repeated administrations at a fixed interval, and has been discontinued from development. A lower dose strength of implant (bimatoprost implant 10 µg, Durysta) is US Food and Drug Administration-approved for single administration.

Single Administration of Bimatoprost Implant: Effects on 24-Hour Intraocular Pressure and 1-Year Outcomes.

PURPOSE: To evaluate the effects of a single bimatoprost implant administration on 24-hour intraocular pressure (IOP) lowering at 8 weeks, and 1-year IOP-lowering efficacy and safety outcomes. DESIGN: Multicenter, open-label, 12-month, phase 3b study (NCT04285580). PARTICIPANTS: Adults with open-angle glaucoma or ocular hypertension. METHODS: Participants (n = 31) received 10-µg bimatoprost implant in the study eye on day 1; IOP (sitting and/or supine) was measured with pneumatonometry every 2 hours throughout a 24-hour period at baseline and week 8. IOP was measured by Goldmann applanation tonometry (GAT) at hour 0 (8 am ± 1 hour) at baseline, weeks 8 and 16, and months 6, 9, and 12. MAIN OUTCOME MEASURES: The primary endpoint was the week-8 hour-matched change from baseline in habitual position IOP over 24 hours assessed with pneumatonometry. Hour 0 IOP change from baseline measured with GAT in study eyes that received no additional (rescue) IOP-lowering treatment, treatment-emergent adverse events (TEAEs), and central corneal endothelial cell density (CECD) were evaluated through 12 months. RESULTS: The mean (standard deviation [SD]) baseline IOP at hour 0 was 24.2 (2.70) mmHg and 25.3 (7.15) mmHg by GAT and pneumatonometry, respectively. Pneumatonometer measurements of IOP taken over 24 hours at week 8 with the participant in habitual position (sitting from 8 am to 10 pm, supine from 12 am to 6 am) showed consistent IOP lowering through the day and night and reduced fluctuation in IOP. The range in IOP measurements over 24 hours was reduced from baseline by a mean (SD) of -1.6 (2.98) mmHg. All 31 bimatoprost implant-treated participants completed the 12-month study; 23 (74%) required no rescue IOP-lowering treatment. The mean (SD) IOP reduction from baseline at month 12 in nonrescued eyes was -4.3 (3.35) mmHg. The most common TEAE was conjunctival hyperemia (incidence 35.5%, 11/31). No implant-treated eye had a ≥ 15% loss in CECD from baseline. CONCLUSIONS: A single intracameral administration of the bimatoprost implant lowered IOP in the habitual position consistently throughout the day and night at week 8. The majority of participants continued to have reduced IOP for 1 year without additional therapy. The 1-year safety profile was favorable. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Single Administration of Intracameral Bimatoprost Implant 10 µg in Patients with Open-Angle Glaucoma or Ocular Hypertension.

INTRODUCTION: This study evaluated the intraocular pressure (IOP)-lowering efficacy and safety of a single intracameral administration of bimatoprost implant 10 µg in adults with open-angle glaucoma or ocular hypertension. METHODS: Two identically designed, randomized, 20-month, parallel-group, phase 3 clinical trials (one study eye/patient) compared three administrations of 10- or 15-µg bimatoprost implant (day 1, weeks 16 and 32) with twice-daily topical timolol maleate 0.5%. An open-label, 24-month, phase 1/2 clinical trial compared one or two implants administered in the study eye with once-daily topical bimatoprost 0.03% in the fellow eye. Separate analyses of the pooled phase 3 and phase 1/2 study datasets evaluated outcomes in the 10-µg bimatoprost implant and comparator treatment arms after a single implant administration, up to the time of implant re-administration or rescue with IOP-lowering medication. RESULTS: In the phase 3 studies, 10-µg bimatoprost implant single administration demonstrated IOP reductions (hour 0) of 4.9-7.0 mmHg through week 15 from a mean (standard deviation, SD) baseline IOP of 24.5 (2.6) mmHg (n = 374); IOP in the topical timolol BID group was reduced by 6.0-6.3 mmHg from a mean (SD) baseline IOP of 24.5 (2.6) mmHg (n = 373). In the phase 1/2 study (n = 21), median time to use of additional IOP-lowering treatment (Kaplan-Meier analysis) was 273 days (approximately 9 months), and 5 of 21 enrolled patients (23.8%) required no additional IOP-lowering treatment up to 24 months after single administration. In each study, after a single implant administration there were no reports of corneal edema, corneal endothelial cell loss, or corneal touch, and no patients had 20% or greater loss in corneal endothelial cell density. CONCLUSIONS: Bimatoprost implant single administration lowers IOP and has a favorable safety profile. Additional studies are needed to further evaluate the duration of effect and factors predicting long-term IOP lowering after a single implant administration. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov NCT02247804, NCT02250651, and NCT01157364.

Comparison of Iridocorneal Angle Assessments in Open-Angle Glaucoma and Ocular Hypertension Patients: Anterior Segment Optical Coherence Tomography and Gonioscopy.

Purpose: To quantitatively compare iridocorneal angle assessments using gonioscopy and anterior segment optical coherence tomography (AS-OCT). Patients: US and Chinese patients with open-angle glaucoma (OAG) and/or ocular hypertension (OHT). Methods: Analysis was pooled from 2 multicenter, noninterventional studies conducted in the US and China. Gonioscopy Shaffer grade and an AS-OCT method that approximates the angle width relative to local morphologic variations were compared by measuring the same iridocorneal angles. A third, separate, single-center, noninterventional study was conducted to verify results observed from the pooled analysis. Results: From the pooled studies, a total of 239 eyes were measured using Shaffer grade and AS-OCT. Of these, 6 were Shaffer grade 2, 37 in Shaffer grade 3, and 196 in Shaffer grade 4. There was a trend of increasing Shaffer grade with increasing AS-OCT angle width. Open iridocorneal angles, Shaffer grade ≥3, had a ~98% sensitivity and 88% positive predictive value for identifying AS-OCT angle width ≥300 µm, using the AS-OCT method. To verify these results, a total of 28 right eyes were imaged for the third study. A trend of increasing Shaffer grade with increasing AS-OCT angle width was observed, and angles with Shaffer grade ≤2 had AS-OCT angle width <300 µm. Conclusion: The AS-OCT method can determine the space in the anterior chamber and can potentially identify angles that are the appropriate size for certain glaucoma devices. Information gathered from AS-OCT can provide additional comprehensive and quantitative assessment to gonioscopy.

Reoperation Rates and Disease Costs for Primary Open-Angle Glaucoma Patients in the United States Treated with Incisional Glaucoma Surgery.

PURPOSE: To evaluate the claims-based 5-year economic and reintervention burden for patients with primary open-angle glaucoma (POAG) after incisional glaucoma surgery in the United States. DESIGN: Retrospective Medicare claims analysis. PARTICIPANTS: One thousand nine hundred forty-five Medicare fee-for-service patients with POAG treated with trabeculectomy, tube shunt, or EX-PRESS shunt procedures from 2010 through 2011. METHODS: Patients with POAG treated with incisional glaucoma surgery (trabeculectomy, tube shunt, or EX-PRESS shunt) from 2010 through 2011 were identified in the Medicare 5% Standard Analytical Files. Ten years of claims data for each patient (2005-2016) were evaluated for prior incisional surgeries and downstream procedures in the treated eye within 5 years of index. Patients' characteristics, downstream procedures, and POAG-related costs were evaluated. Proportions of patients with downstream procedures in the index eye indicating failure of the index surgery, glaucoma reoperations, nonfailure complications, interventions, or cataract surgery were assessed over 5 years of follow-up. MAIN OUTCOME MEASURES: Cumulative rates of index surgery failure and glaucoma reoperations over 5 years after incisional glaucoma surgery. RESULTS: Of 1945 patients, 223 underwent EX-PRESS shunt, 551 underwent tube shunt, and 1171 underwent trabeculectomy at index. Rates of failure, glaucoma reoperations, or nonfailure complications rose over 5 years after index for all patient subgroups. At 1 year, 15.1% of EX-PRESS shunt patients, 11.6% of tube shunt patients, and 8.8% of trabeculectomy patients had experienced failure based on postindex procedures. By 5 years follow-up, these rates were 31.5% of EX-PRESS shunt patients, 27.1% of tube shunt patients, and 23.5% of trabeculectomy patients. Five-year rates of glaucoma reoperations were 18.3%, 14.0%, and 15.1%, respectively. Among tube shunt and trabeculectomy patients with prior incisional surgery, the 5-year failure rates were 32.5% and 32.6%, and reoperations rates were 12.0% and 26.1%, respectively. CONCLUSIONS: More than one-fourth of patients with POAG treated with incisional surgery underwent additional procedures to address index surgery failure within 5 years. Of these, more than half underwent additional incisional glaucoma surgery. These outcomes from clinical practice settings demonstrate that patients with POAG who require incisional surgery continue to need additional safe and effective surgical treatment options to manage their glaucoma.

A novel bilayered expanded polytetrafluoroethylene glaucoma implant creates a permeable thin capsule independent of aqueous humor exposure.

The purpose of these studies was to evaluate clinical, functional, and histopathological features of glaucoma drainage implants (GDIs) fabricated from novel, custom-tailored expanded polytetrafluoroethylene (ePTFE). Implants of matching footprints were fabricated from silicone (Control) and novel, bilayered ePTFE. ePTFE implants included: (a) one that inflated with aqueous humor (AH) (High), (b) one that inflated with a lower profile (Low), (c) an uninflated implant not connected to the anterior chamber (Flat), and (d) one filled with material that did not allow AH flow (Filled). All implants were placed in adult New Zealand White rabbits and followed over 1-3 months with clinical exams and intraocular pressure. The permeability of tissue capsules surrounding GDIs was assessed using constant-flow perfusion with fluoresceinated saline at physiologic flow rates. After sacrifice, quantitative histopathological measures of capsule thickness were compared among devices, along with qualitative assessment of cellular infiltration and inflammation. Capsular thickness was significantly reduced in blebs over ePTFE (61.4 ± 53 µm) versus silicone implants (193.6 ± 53 µm, p = .0086). AH exposure did not significantly alter capsular thickness, as there was no significant difference between High and Filled (50.9 ± 29, p = .34) implants. Capsules around ePTFE implants demonstrated permeability with steady-state pressure: flow relationships at physiologic flow rates and rapid pressure decay with flow cessation, while pressure in control blebs increased even at low flow rates and showed little decay. Perfused fluorescein dye appeared beyond the plate border only in ePTFE implants. ePTFE implants are associated with thinner, more permeable capsules compared to silicone implants simulating presently used devices.

Comparison of Clinical Outcomes with Open Versus Closed Conjunctiva Implantation of the XEN45 Gel Stent.

PURPOSE: To describe the efficacy and safety of open versus closed conjunctival implantation of the XEN45 Gel Stent (Allergan Inc). DESIGN: Retrospective, multicenter study. PARTICIPANTS: A total of 137 patients with glaucoma who underwent XEN45 implantation via open or closed conjunctival methods. The XEN45 was implanted as a stand-alone procedure or at the time of cataract surgery by 5 surgeons. METHODS: Patient demographics, diagnoses, preoperative and postoperative clinical data, outcome measures including intraocular pressure (IOP), use of glaucoma medications, visual acuity, and complications were collected. Statistical analyses were performed with P < 0.05 as significant. MAIN OUTCOME MEASURES: Failure was defined as less than 20% reduction of IOP from medicated baseline or IOP >21 mmHg at 2 consecutive visits at postoperative month 1 and beyond, the need for subsequent operative intervention or additional glaucoma surgery, or a catastrophic event such as loss of light perception. Eyes that had not failed by these criteria and were not on glaucoma medications were considered complete successes. Eyes that had not failed but required glaucoma medications were defined as qualified successes. RESULTS: Complete success was achieved in 31% and 56% of the closed and open groups, respectively (P = 0.01). Qualified success was achieved in 53% and 71% of the closed and open groups, respectively (P = 0.06). At postoperative month 12, the open conjunctiva group was using fewer glaucoma medications than the closed group (0.9 vs. 1.8, respectively; P = 0.02). At postoperative month 12, the open group had a significantly greater percentage of IOP reduction compared with the closed group (43.1% vs. 24.8%, respectively; P = 0.02). Postoperative needling rates were higher in the closed group compared with the open group (36.1% vs. 11.8%, P = 0.001). CONCLUSIONS: Implantation of the XEN45 with opening of the conjunctiva is a safe and efficacious procedure to lower IOP with comparable success rate and lower needling rate compared with the closed conjunctiva technique. Prospective evaluation of the various methods for XEN45 implantation will allow for further comparison.

XEN Gel Stent Open Conjunctiva Technique: A Practical Approach Paper.

The Xen Gel Stent lowers intraocular pressure by shunting aqueous humor to the subconjunctival space. While published studies include both open conjunctiva and closed conjunctiva approaches, most publications feature a closed conjunctiva, ab interno approach. While this approach is widely used, other approaches may be preferred for some patients. This paper provides details on surgical steps and tips for enhancing outcomes for an open conjunctiva technique for the implantation of the Xen Gel Stent, as well as reasoning as to when this approach should be used.

Evolving Guidelines for Intracameral Injection.

PURPOSE: To review evidence and provide guidelines on intracameral (ICM) injection techniques and monitoring. MATERIALS AND METHODS: A review of published literature on ICM injection and intravitreal injections formed the basis for roundtable deliberations by an expert panel of ophthalmologists. RESULTS: ICM injection as a way to deliver medications is growing in popularity. However, there is limited published literature and no standard approach to best practices for ICM injections, particularly when not accompanying another surgical procedure. Fortunately, there is long clinical experience with ICM manipulation and a large body of evidence surrounding intravitreal injections that has provided important guidance. The expert panel formulates several concrete guidelines and many suggested techniques to help physicians safely and effectively employ ICM injections. CONCLUSIONS: This committee addressed the many considerations surrounding ICM injection of drugs or implants and agree that it is a safe and effective surgical procedure when performed with appropriate training and according to established safe practices.

24-Month Phase I/II Clinical Trial of Bimatoprost Sustained-Release Implant (Bimatoprost SR) in Glaucoma Patients.

OBJECTIVE: The objective of this study was to evaluate the safety and intraocular pressure (IOP)-lowering effects over 24 months of biodegradable bimatoprost sustained-release implant (Bimatoprost SR) administration versus topical bimatoprost 0.03% in patients with open-angle glaucoma (OAG). METHODS: This was a phase I/II, prospective, 24-month, dose-ranging, paired-eye controlled clinical trial. At baseline following washout, adult patients with OAG (N = 75) received Bimatoprost SR (6, 10, 15, or 20 µg) intracamerally in the study eye; the fellow eye received topical bimatoprost 0.03% once daily. Rescue topical IOP-lowering medication or single repeat administration with implant was permitted. The primary endpoint was IOP change from baseline. Safety measures included adverse events (AEs). RESULTS: At month 24, mean IOP reduction from baseline was 7.5, 7.3, 7.3, and 8.9 mmHg in eyes treated with Bimatoprost SR 6, 10, 15, and 20 µg, respectively, versus 8.2 mmHg in pooled fellow eyes; 68, 40, and 28% of pooled study eyes had not been rescued/retreated at months 6, 12, and 24, respectively. AEs in study eyes that occurred ≤ 2 days post-procedure typically were transient. After 2 days post-procedure, overall AE incidence was similar between study and fellow eyes, with some events typically associated with topical prostaglandin analogs having lower incidence in study eyes. CONCLUSIONS: Bimatoprost SR showed favorable efficacy and safety profiles up to 24 months, with all evaluated dose strengths demonstrating overall IOP-reducing effects comparable to those of topical bimatoprost. Targeted and sustained delivery of bimatoprost resulted in protracted IOP lowering, suggesting that Bimatoprost SR may represent a transformational new approach to glaucoma therapy. Clinicaltrials.gov identifier: NCT01157364.

Bimatoprost Sustained-Release Implants for Glaucoma Therapy: 6-Month Results From a Phase I/II Clinical Trial.

PURPOSE: To evaluate the safety and intraocular pressure (IOP)-lowering effect of a biodegradable bimatoprost sustained-release implant (Bimatoprost SR). DESIGN: Phase I/II, prospective, 24-month, dose-ranging, paired-eye controlled clinical trial. METHODS: At baseline following washout, open-angle glaucoma patients (n = 75) were administered Bimatoprost SR (6 µg, 10 µg, 15 µg, or 20 µg) intracamerally in the study eye; the fellow eye began topical bimatoprost 0.03% once daily. Rescue topical IOP-lowering medication or a single repeat treatment with implant was allowed. The primary endpoint was IOP change from baseline. The main safety measure was adverse events. Results through month 6 are reported. RESULTS: Bimatoprost SR provided rapid, sustained IOP lowering. Overall mean IOP reduction from baseline through week 16 in study eyes was 7.2, 7.4, 8.1, and 9.5 mm Hg with the 6-µg, 10-µg, 15-µg, and 20-µg dose strengths of implant, respectively, vs 8.4 mm Hg in topical bimatoprost-treated pooled fellow eyes (data censored at rescue/retreatment). Rescue/retreatment was not required in 91% and 71% of study eyes up to week 16 and month 6, respectively. Adverse events in study eyes usually occurred within 2 days after the injection procedure and were transient. Conjunctival hyperemia with onset later than 2 days after the injection procedure was more common with topical bimatoprost than Bimatoprost SR (17.3% vs 6.7% of eyes). CONCLUSIONS: Bimatoprost SR demonstrated favorable efficacy and safety through 6 months. All dose strengths were comparable to topical bimatoprost in overall IOP reduction through week 16. A single administration controlled IOP in the majority of patients for up to 6 months.

Bottle Characteristics of Topical International Glaucoma Medications versus Local Brands in Saudi Arabia.

WHAT IS KNOWN AND OBJECTIVE: Physical bottle characteristics differ of brand name topical glaucoma medications and local generic equivalents. This study compares the bottle characteristics of international topical glaucoma brands versus local brands from the Kingdom of Saudi Arabia. METHODS: Data were collected on bottle drum volume, drop volume, bottle squeezability, bottle tip diameter, labels and instructions, cap color coding, and clarity of the drug label. Density-based calculations of drops in bottle volume were assessed using an analytic balance. Bottle tip diameter was measured using 0.05 mm Vernier calipers. A Likert scale-based questionnaire was used to evaluate the subjective opinions of patients on bottle squeezability, clarity of usage and storage instructions, and the consistency of the cap color coding. RESULTS: The volumes of international brands were statistically significantly higher than the local brands (P < 0.001). A number of drops per bottle and tip diameter were comparable between the international local brands. Cap color coding was inconsistent for international and local brands. Patients were dissatisfied with the label font size. Patients reported that the international and local brands were similar in terms of the ease of opening the bottle, instilling a drop, and the clarity of the instructions; but the local brands were subjectively easier to squeeze than international brands. WHAT IS NEW AND CONCLUSIONS: This is the first study to compare bottle characteristics of local Saudi Arabia brands with international brands. The bottle characteristics and patient feedback were similar between the local and international topical glaucoma medications. However, there were differences between the local and international brands in drug volume, bottle squeezability. Hence, patient compliance and drop dosage may differ based on the origin of manufacture.

Retrobulbar Injections for Blind Painful Eyes: A Comparative Study of Retrobulbar Alcohol Versus Chlorpromazine.

PURPOSE: The purpose of the study was to evaluate 2 agents used during retrobular injections to relieve pain in blind eyes. METHODS: This masked prospective randomized study compared retrobulbar injections for blind painful eyes that were divided into 2 groups: eyes in group 1 (G-I) received 1.5 mL of absolute alcohol (ethanol) and those in group 2 (G-II) received 1.5 mL of chlorpromazine (25 mg/mL). The pain was graded before, during, and after intervention using a verbal numeric visual analog scale. Intraocular pressure (IOP) and adverse events were also recorded. Complete success was defined as no pain after injection. Treatment failures were classified as further intervention (evisceration-enucleation) or no change in visual analog scale pain scores. RESULTS: Both groups included 16 patients each. Complete success was achieved in 7 of 16 (43.7%) patients in G-I and in 6 of 16 (37.5%) in G-II. The failure rate was 5 of 16 (31.3%) in G-I and 6 of 16 (37.5%) in G-II. Postoperative adverse events occurred in 33.3% of patients in G-I and 56% of patients in G-II. Transient eyelid edema was more prominent in G-II. Reduction in IOP occurred after injection in both groups. In G-I, IOP decreased from a mean of 24.3 to 14 mm Hg. In G-II, IOP decreased from 27 to 15 mm Hg. Five of the 7 (71.4%) patients with initial IOP>45 mm Hg suffered from severe pain. After injection, only 1 patient with an IOP>27 mm Hg had moderate pain. CONCLUSIONS: Retrobulbar alcohol or chlorpromazine decreased IOP and reduced pain in approximately two-thirds of blind painful eyes with few postoperative complications. However, 33% of patients required further intervention to manage pain.

Two-Year COMPASS Trial Results: Supraciliary Microstenting with Phacoemulsification in Patients with Open-Angle Glaucoma and Cataracts.

PURPOSE: We evaluated 2-year safety and efficacy of supraciliary microstenting (CyPass Micro-Stent; Transcend Medical, Inc., Menlo Park, CA) for treating mild-to-moderate primary open-angle glaucoma (POAG) in patients undergoing cataract surgery. DESIGN: Multicenter (24 US sites), interventional randomized clinical trial (RCT) (ClinicalTrials.gov identifier, NCT01085357). PARTICIPANTS: Subjects were enrolled beginning July 2011, with study completion in March 2015. Subjects had POAG with mean diurnal unmedicated intraocular pressure (IOP) 21-33 mmHg and were undergoing phacoemulsification cataract surgery. METHODS: After completing cataract surgery, subjects were intraoperatively randomized to phacoemulsification only (control) or supraciliary microstenting with phacoemulsification (microstent) groups (1:3 ratio). Microstent implantation via an ab interno approach to the supraciliary space allowed concomitant cataract and glaucoma surgery. MAIN OUTCOME MEASURES: Outcome measures included percentage of subjects achieving ≥20% unmedicated diurnal IOP lowering versus baseline, mean IOP change and glaucoma medication use, and ocular adverse event (AE) incidence through 24 months. RESULTS: Of 505 subjects, 131 were randomized to the control group and 374 were randomized to the microstent group. Baseline mean IOPs in the control and microstent groups were similar: 24.5±3.0 and 24.4±2.8 mmHg, respectively (P > 0.05); mean medications were 1.3±1.0 and 1.4±0.9, respectively (P > 0.05). There was early and sustained IOP reduction, with 60% of controls versus 77% of microstent subjects achieving ≥20% unmedicated IOP lowering versus baseline at 24 months (P = 0.001; per-protocol analysis). Mean IOP reduction was ↓7.4 mmHg for the microstent group versus ↓5.4 mmHg in controls (P < 0.001), with 85% of microstent subjects not requiring IOP medications at 24 months. Mean 24-month medication use was 67% lower in microstent subjects (P < 0.001); 59% of control versus 85% of microstent subjects were medication free. Mean medication use in controls decreased from 1.3±1.0 drugs at baseline to 0.7±0.9 and 0.6±0.8 drugs at 12 and 24 months, respectively, and in the microstent group from 1.4±0.9 to 0.2±0.6 drugs at both 12 and 24 months (P < 0.001 for reductions in both groups at both follow-ups vs. baseline). No vision-threatening microstent-related AEs occurred. Visual acuity was high in both groups through 24 months; >98% of all subjects achieved 20/40 best-corrected visual acuity or better. CONCLUSIONS: This RCT demonstrated safe and sustained 2-year reduction in IOP and glaucoma medication use after microinterventional surgical treatment for mild-to-moderate POAG.

Trabecular micro-bypass shunt (iStent®): basic science, clinical, and future).

The trabecular bypass stent offers an alternative to filtration surgery. Patients who may be ideal candidates for considering this procedure are those with prior conjunctival surgery; for example, those who had a 360° peritomy from a scleral buckle might not do well with a trabeculectomy and there is no space for a tube. Highly myopic patients do not tolerate hypotony well, and the iSTB may be an option for some of these patients. I have used the iSTB in patients on anticoagulants who could not stop them, and they needed something beyond medications and laser to lower the IOP in subjects with open-angle glaucoma. Young patients, especially those with one eye, who need rapid visual recovery (for instance to return to work) may be good candidates to consider the iSTB as well. Because of the position used for clear corneal cataract surgery, the temporal approach is best for doing these. Therefore, if you are doing cataract surgery on someone who needs a lower IOP, you already are in the correct position to implant the devices. Patients may need some medications after the procedure to lower the IOP to the level desired. The results from Armenia are encouraging, given an IOP of 11.8 mmHg after 2 iSTB stents and taking daily travoprost. These results are difficult to reach even with a trabeculectomy. When selecting your fist patients, avoid those with the congested episcleral veins, look for patients with wide open angles, and if you can see aqueous veins at the slit-lamp it may indicate a viable outflow system. Probably avoid patients with IOPs over 35 mmHg. The micro-invasive trabecular bypass stents offer an alternative surgical intervention for select patients with open-angle glaucoma. Recent studies show that combining these micro-stents with medications can lead to as low of an intraocular pressure (IOP) as is achieved by many more invasive incisional surgeries. The technique is quite precise and learning the procedure is similar to clear corneal phacoemulsification followed by a goniotomy. Long-term data are starting to come in and the safety is favorable. The IOP success appears to be based on the patency of the outflow system for a given patient. Key factors in determining the success involve the placement of trabecular bypass devices into the canal of Schlemm and require a down-stream patency of the collector channel system and a low episcleral venous pressure. Because accessing the collector system may require placement by a patent channel, the placement of two stents, a longer stent with scaffolding or somehow imaging the outflow system may lead to the best control of the IOP.

Critical appraisal of loteprednol ointment, gel, and suspension in the treatment of postoperative inflammation and pain following ocular and corneal transplant surgery.

PURPOSE: To review comprehensively the available peer-reviewed published articles in the literature on loteprednol suspension, gel, and ointment in the treatment of ocular inflammation and pain following ocular surgery. METHODS: We conducted a PubMed literature search review of all published articles on keywords associated with loteprednol etabonate and ocular surgery. RESULTS: A total of 59 peer-reviewed articles were found in the literature. The focus of the majority of the articles was on the safety and efficacy of loteprednol etabonate 0.5% in postoperative control of inflammation and pain following cataract surgery. There were only three articles with a remote association between loteprednol etabonate and keratoplasty. CONCLUSION: Lotemax® ointment may also have potential as a first-line anti-inflammatory agent of choice in postoperative settings of strabismus and penetrating glaucoma, and following low-risk penetrating keratoplasty procedures.

Cataract surgery with trabecular micro-bypass stent implantation in patients with mild-to-moderate open-angle glaucoma and cataract: two-year follow-up.

PURPOSE: To assess the long-term safety and efficacy of a single trabecular micro-bypass stent with concomitant cataract surgery versus cataract surgery alone for mild to moderate open-angle glaucoma. SETTING: Twenty-nine investigational sites, United States. DESIGN: Prospective randomized controlled multicenter clinical trial. METHODS: Eyes with mild to moderate glaucoma with an unmedicated intraocular pressure (IOP) of 22 mm Hg or higher and 36 mm Hg or lower were randomly assigned to have cataract surgery with iStent trabecular micro-bypass stent implantation (stent group) or cataract surgery alone (control group). Patients were followed for 24 months postoperatively. RESULTS: The incidence of adverse events was low in both groups through 24 months of follow-up. At 24 months, the proportion of patients with an IOP of 21 mm Hg or lower without ocular hypotensive medications was significantly higher in the stent group than in the control group (P=.036). Overall, the mean IOP was stable between 12 months and 24 months (17.0 mm Hg ± 2.8 [SD] and 17.1 ± 2.9 mm Hg, respectively) in the stent group but increased (17.0 ± 3.1 mm Hg to 17.8 ± 3.3 mm Hg, respectively) in the control group. Ocular hypotensive medication was statistically significantly lower in the stent group at 12 months; it was also lower at 24 months, although the difference was no longer statistically significant. CONCLUSIONS: Patients with combined single trabecular micro-bypass stent and cataract surgery had significantly better IOP control on no medication through 24 months than patients having cataract surgery alone. Both groups had a similar favorable long-term safety profile. FINANCIAL DISCLOSURE: Dr. Craven was an investigator in the clinical trial of the iStent. Dr. Katz is a consultant to Glaukos and was the medical monitor for the clinical trial of the iStent. Dr. Katz is a stockholder in Glaukos. Mr. Wells and Ms. Giamporcaro are employees of Glaukos.

A randomized, controlled comparison of macroscopic conjunctival hyperemia in patients treated with bimatoprost 0.01% or vehicle who were previously controlled on latanoprost.

PURPOSE: To evaluate conjunctival hyperemia associated with bimatoprost 0.01% treatment in patients who replace latanoprost 0.005% with bimatoprost 0.01%. METHODS: Randomized, double-masked, vehicle-controlled, multicenter study of patients with ocular hypertension or glaucoma whose intraocular pressure (IOP) was adequately controlled on latanoprost monotherapy. At baseline, patients discontinued latanoprost and were randomized to treatment with once-daily bimatoprost 0.01% (n = 151) or vehicle (n = 71). The primary endpoint was the peak change in macroscopic hyperemia (conjunctival hyperemia evaluated by gross visual inspection) from baseline to month 1. RESULTS: Bimatoprost 0.01% was noninferior to vehicle in the mean [standard deviation] peak change from baseline macroscopic hyperemia at month 1 (0.18 [0.46] in the bimatoprost 0.01% group vs 0.02 [0.32] in the vehicle group, P = 0.009). The between-group difference was 0.15 (95% confidence interval [CI]: 0.04, 0.26), which was within the predefined margin for noninferiority of 0.5 on a hyperemia grading scale of 0 to +3. There were no statistically significant between-group differences in the percentage of patients with a ≥1-grade increase in macroscopic hyperemia from baseline. Mean IOP was decreased from baseline (-0.7 to -1.3 mm Hg) in the bimatoprost 0.01% group (P ≤ 0.002) and was increased from baseline (+3.3 to +3.6 mm Hg) in the vehicle group (P < 0.001) at month 1. There were no statistically significant between-group differences in adverse events. CONCLUSIONS: Bimatoprost 0.01% was noninferior to vehicle with respect to conjunctival hyperemia in this study population. Replacement of latanoprost with bimatoprost 0.01% in patients with ocular hypertension or glaucoma can result in additional IOP reduction without clinically important hyperemia.