Minimally Invasive Glaucoma Surgery: Latest Developments and Future Challenges.

The development of minimally invasive glaucoma surgeries (MIGSs) was intended to provide safe and modestly efficacious modalities for early intervention of mild-to-moderate glaucoma, with minimal trauma and rapid recovery. They were mainly ab interno procedures that reduce intraocular pressure by facilitating the aqueous outflow by bypassing the trabecular meshwork resistance, reinforcing the uveoscleral flow via the supraciliary space, and reducing aqueous production by the ciliary body. While the cumulating evidence helps shape the role of the available MIGS, the exponential new development and advancement in this field has expanded the territory of MIGS. Apart from developing subconjunctival MIGS filtration devices (Xen gel stent and PRESERFLO MicroShunt), there is a tendency to revisit the "traditional" MIGS for alternative use and to modify the procedures with consideration of the fundamental aqueous outflow physiology. Combined MIGS has also been suggested, based on the theory that their different mechanisms may provide additive or synergistic effects. The advancement of laser procedures is also promising and could supplement unmet needs along the glaucoma treatment algorithm. This review examines the broad array of MIGS, updates the recent findings, discusses their potential alternative applications, and explores future challenges.

36-Month Outcomes from the Prospective GEMINI Study: Canaloplasty and Trabeculotomy Combined with Cataract Surgery for Patients with Primary Open-Angle Glaucoma.

Purpose: To provide long-term intraocular pressure (IOP) and ocular hypotensive medication usage outcomes through 36 months for patients treated with canaloplasty and trabeculotomy (OMNI Surgical System) combined with cataract surgery as participants in the GEMINI study. Setting: Eleven ophthalmology practices in 10 US states. Design: Non-interventional 36-month extension of the 12-month, prospective, multicenter, GEMINI study. Methods: GEMINI patients had visually significant cataract, mild-to-moderate glaucoma (ICD-10 guidelines), medicated IOP <33 mmHg, and unmedicated mean diurnal IOP (DIOP) (after washout) 21-36 mmHg. Patients from GEMINI were eligible for inclusion. Outcome measures were reduction in mean unmedicated DIOP, reduction in mean IOP-lowering medications, percent of eyes with ≥20% reduction in unmedicated DIOP, and percent of eyes with unmedicated DIOP ≥6 and ≤18 mmHg. Results: A total of 66 patients provided consent and were enrolled. Mean (SD) unmedicated DIOP was 23.1 (2.7) mmHg at baseline, 16.7 (4.1), 16.3 (3.3) at 24 and 36 months; mean reductions of 6.2 (4.1) and 6.9 (3.4) mmHg. Twelve-month IOP at the end of GEMINI was 15.6 mmHg. The proportion of eyes with ≥20% reduction in IOP was 77% and 78% (months 24 and 36) compared to 87% at month 12 from GEMINI. About 68% of patients had an IOP between 6 and 18 mmHg at 24 months and 71% at 36 months. Mean IOP-lowering medications was 1.7 at baseline, which was reduced to 0.4 (24 months, -1.3) and 0.3 (36 months, -1.4). About 74% of patients (46 of 62) were medication free at 36 months. Conclusion: GEMINI demonstrated 12-month effectiveness of canaloplasty and trabeculotomy with OMNI combined with cataract surgery for IOP and medication reduction in mild-to-moderate glaucoma. However, longer-term data is key to the decision making in the selection of a surgical treatment. This GEMINI extension demonstrates that the 12-month outcomes from GEMINI were sustained through 36 months.

A Randomized, Controlled Trial Comparing Tearcare® and Cyclosporine Ophthalmic Emulsion for the Treatment of Dry Eye Disease (SAHARA).

Purpose: We compare outcomes in eyes with dry eye disease (DED) treated with TearCare (TC) or topical cyclosporine 0.05% (RESTASIS; CsA). Setting: Nineteen ophthalmic and optometric practices in 11 US states. Design: Multicenter, randomized, assessor-masked, controlled IRB-approved trial. Eligible subjects: ≥22 years of age, dry eye symptoms within 3-6 months, Tear Break-up Time (TBUT) ≥1 to ≤7 s, Meibomian Gland Secretion Score (MGSS) ≤12, Ocular Surface Disease Index (OSDI) of 23-79. Randomized (1:1) to TC or CsA. TC subjects treated at baseline and month 5; CsA was twice daily for 6 months. Methods: Follow-up visits were scheduled for Day 1, Week 1, Months 1, 3, and 6 with primary inference at Month 6. Primary outcomes: TBUT and OSDI; secondary outcomes: MGSS, conjunctival and corneal staining, eye dryness score (EDS), symptoms assessment in dry eye (SANDE) score, and Schirmer tear score (STS). Safety assessments included adverse events, best corrected visual acuity, intraocular pressure, and slit-lamp findings. Results: Overall, 345 subjects, 172 TC and 173 CsA. TBUT improved at all time points in both groups (p<0.0001), with statistically greater improvement for TC versus CsA (p=0.0006). OSDI improved significantly at all time points in both groups (p<0.0001) with no significant differences between treatments. MGSS and other measures of meibomian gland function improved significantly more with TC eyes versus CsA; other secondary outcomes showed significant improvements in both groups with no difference between groups. Treatment-related adverse events were uncommon (10 total, 8 in the CsA group consistent with prior CsA studies); most (9/10) mild. Conclusion: TC provides statistically superior and sustained improvement in TBUT and multiple measures of meibomian gland secretion, and non-inferior improvement in OSDI, corneal and conjunctival staining, SANDE, EDS, and STS versus CsA. TC should be a preferred treatment for DED associated with MGD.

Canaloplasty and Trabeculotomy with the OMNI System in Patients with Open-Angle Glaucoma: Two-Year Results from the ROMEO Study.

Purpose: To provide extended safety and effectiveness follow-up for eyes treated with circumferential canaloplasty and trabeculotomy (CP+TR) that were included in the 12-month ROMEO study. Setting: Seven multi-subspecialty ophthalmology practices located in 6 states (Arkansas, California, Kansas, Louisiana, Missouri, and New York). Design: Retrospective, multicenter, IRB approved. Subjects: Eligible eyes had mild-moderate glaucoma and were treated with CP+TR with cataract surgery or as a standalone intervention. Methods: Main outcome measures were mean IOP, mean number of ocular hypotensive medications, mean change in number of medications, proportion of patients with a ≥20% reduction in IOP or with IOP ≤18 mmHg, and proportion of patients medication free. Safety outcomes were adverse events and secondary surgical interventions (SSI). Results: Eight surgeons at 7 centers contributed 72 patients stratified by pre-operative intraocular pressure (IOP); >18 mmHg (Grp1), ≤18 mmHg (Grp2). Mean follow-up of 2.1 years (min 1.4, max 3.5). 2-year IOP (SD) was 15.6 mmHg (-6.1 mmHg, -28% from baseline) on 1.4 medications (-0.9, -39%) for Grp1 with cataract surgery; 14.7 mmHg (-7.4 mmHg, -33% from baseline) on 1.6 medications (-0.7, -15%) for Grp1 standalone, 13.7 mmHg (-0.6 mmHg, -4.2%) on 1.2 medications (-0.8, -35%) for Grp2 with cataract surgery, 13.3 mmHg (-2.3 mmHg, -14.7%) on 1.2 medications (-1.0, -46%) for Grp2 standalone. The proportion of patients at 2 years with either a ≥20% IOP reduction or IOP between 6 and 18 mmHg and no increase in medication or SSI was 75% (54 of 72, 95% CI 69.9%, 80.1%). One-third of patients (24 of 72) were medication free whereas 9 of 72 were pre-surgical. No device-related adverse events during extended follow-up; 6 eyes (8.3%) required additional surgical or laser intervention for IOP control after 12 months. Conclusion: CP+TR provides effective IOP control that is sustained for 2 years or more.

Systematic Literature Review of Clinical, Economic, and Humanistic Outcomes Following Minimally Invasive Glaucoma Surgery or Selective Laser Trabeculoplasty for the Treatment of Open-Angle Glaucoma with or Without Cataract Extraction.

Introduction: Selective laser trabeculoplasty (SLT) and minimally invasive glaucoma surgery (MIGS) are increasingly used options for mild-to-moderate open-angle glaucoma (OAG) care. While most MIGS devices are indicated for use in combination with cataract surgery only, with phacoemulsification playing a role in lowering IOP, newer technologies can also be used as standalone glaucoma surgery. Methods: This systematic literature review (SLR) aimed to assess the clinical, economic, and humanistic outcomes of MIGS and SLT for the treatment of OAG and was conducted according to PRISMA guidelines. Studies that assessed MIGS or SLT in at least one treatment arm versus any other glaucoma treatment in adults with mild-to-moderate OAG were included. Clinical, humanistic (health-related quality of life [HRQoL] and patient burden), and economic data were extracted, and the methodological quality of included studies was evaluated. Results: A total of 2720 articles were screened, and 81 publications were included. Fifty-eight reported clinical outcomes. The majority assessed iStent or iStent inject (n=41), followed by OMNI (n=9), gonioscopy-assisted transluminal trabeculotomy (GATT) or the Kahook Dual Blade (KDB) (n=7), Hydrus (n=6), SLT (n=5), Xen Gel Stent (n=2), PreserFlo (n=1), and iTrack (n=1). IOP reduction was observed across prospective studies, varying from -31% to -13.7% at month 6 and from -39% to -11.4% at year 1 versus baseline. Most adverse events were transient and non-serious. Limited humanistic and economic data were identified. Conclusion: Given their established efficacy and safety, there is a rationale for wider use of MIGS in mild-to-moderate OAG. Of the MIGS devices, iStent and OMNI have the largest clinical evidence base supporting their sustained effectiveness.

Canaloplasty and trabeculotomy with the OMNI® surgical system in OAG with prior trabecular microbypass stenting.

PURPOSE: Evaluate effectiveness and safety outcomes for patients treated with canaloplasty and trabeculotomy previously treated with a trabecular microbypass stent (TBS). METHODS: Retrospective, multicenter, IRB approved study. Patients treated with TBS (iStent/iStent inject, Glaukos) and subsequently with OMNI surgical system (OSS) (Sight Sciences). From 5 practices in 5 US states. Open-angle glaucoma (OAG), minimum 3 months follow-up after OSS surgery, Pre-OSS IOP ≥ 17 mmHg on ≥ 1 medication. No glaucoma procedures between TBS and OSS. ENDPOINTS: proportion with ≥ 20% reduction in IOP, IOP between 6 and 18 mmHg, mean IOP, change in IOP, mean number of medications. Adverse events and secondary surgical interventions (SSI). Mann-Whitney rank sum test compared pre-OSS IOP and medications with follow-up. RESULTS: Twenty seven patients. Average age (SD) 72.2 (10.8), 22/27 primary OAG (82%), mean MD - 6.2 (7.0) dB. Mean IOP before OSS 22.3 (4.3) mmHg on 2.2 (1.3) medications. At last follow-up (mean 11 months) IOP was 17.2 mmHg on 1.8 medications, - 5.1 mmHg (- 23%, p < .001), - 0.4 meds (- 18%, p = .193); ≥ 20% IOP reduction (41%), IOP ≤ 18 (56%). Adverse events were non-serious. Hyphema > 1 mm (3, 11%), BCVA decrease (4, 15%), IOP spike (2, 7%). SSI (4, 15%) had higher pre-OSS IOP (23.4 mmHg) and worse MD (- 9.6 dB). CONCLUSION: Patients uncontrolled by medication and a prior TBS would once have been candidates for trabeculectomy and tube shunts. OSS offered a minimally invasive option that provided IOP control and avoidance of traditional surgery for the majority over follow-up averaging 11 months and up to 42 months.

A Multicenter 12-Month Retrospective Evaluation of Canaloplasty and Trabeculotomy in Patients with Open-Angle Glaucoma: The ROMEO 2 Study.

Purpose: Twelve-month safety and effectiveness results for canaloplasty combined with trabeculotomy using the OMNI surgical system in pseudophakic eyes or combined with cataract surgery in mild-to-moderate open-angle glaucoma (OAG). Setting: Sixteen centers in 11 US states (AL, AR, CA, CT, KS, LA, MO, NY, SD, TN, TX). Design: Retrospective, case series, open-label. Methods: A total of 136 eligible patients from 20 surgeons: mild-to-moderate OAG (visual field mean deviation (MD) not worse than -12 dB), 12-month follow-up, preoperative medicated IOP >18 mmHg and ≤36 mmHg on ≤5 medications. One eye per patient enrolled. Endpoints included proportion with ≥20% reduction in IOP or IOP between 6 and 18 mmHg (inclusive) and on the same or fewer medications without secondary surgical intervention (SSI) (primary success), mean IOP, change in IOP, ocular hypotensive medication use, and proportion of patients with a 20% or greater reduction in IOP at 12 months. Safety: adverse events (AE) and best corrected visual acuity (BCVA). Results: Primary success was met by 71%. Mean IOP was reduced (22.3-15.9 mmHg, p < 0.0001). Medications went from 1.9 ± 1.3 to 1.3 ± 1.2 (p < 0.001). AE were mild and as expected for angle surgery. The most frequent AE were BCVA loss (6%), mild inflammation (4%), IOP elevation (3%), and clinically significant hyphema (3%). There were 4 (3%) SSI. Conclusion: The OMNI system provides effective IOP reduction, sustained IOP control, and meaningful medication reduction for up to 12 months postoperative. The present study confirms and extends the results from ROMEO.

Suppression of Diurnal (9AM-4PM) IOP Fluctuations with Minimally Invasive Glaucoma Surgery: An Analysis of Data from the Prospective, Multicenter, Single-Arm GEMINI Study.

PURPOSE: This study analyzes diurnal IOP data (9AM, 12PM, 4PM) from a prospective 12-month trial of the OMNI Surgical System in open-angle glaucoma (OAG) patients with the aim of evaluating effect of MIGS surgery on the amplitude of the diurnal IOP profile pre- and postoperatively. SETTING: Fifteen ophthalmology practices and surgery centers located in 14 states in the United States. DESIGN: Prospective, multicenter, IRB approved study. Patients treated with canaloplasty (360°) and trabeculotomy (180°). Patients had cataract and mild-moderate OAG with intraocular pressure (IOP) ≤33 mmHg on zero to four hypotensive medications. METHODS: Post-hoc analysis of diurnal IOP data from the multicenter GEMINI study. Analysis includes comparison of IOP preoperatively and at month 12 for each of the diurnal time points, 9AM, 12PM, 4PM, change in magnitude of spread between the maximum IOP and minimum IOP for each patient and the proportions of patients preoperatively and at month 12 with IOPs at or below 25, 21, 18, and 15 mmHg, average variability (standard deviation of the 9AM, 12PM, and 4PM IOP) preoperatively and at month 12. RESULTS: A total of 128 patients included in this analysis. IOP at each diurnal timepoint was significantly lower postoperatively (p<0.0001). The difference between highest and lowest IOP measurement for each patient averaged 2.8 mmHg preoperatively (SD 2.4, MAX 14, MIN 0) and 1.8 mmHg (SD 1.7, MAX 10, MIN 0) month 12 (P<0.00001). The proportion with IOP ≤ to 25, 21, 18, and 15 mmHg increased; 75%-97%, 27%-88%, 1%-79%, and <1%-56%, respectively. The average variability was greater at all time points preoperatively (P<0.0001). CONCLUSION: This study demonstrates that eyes with OAG can benefit from an overall decreased IOP and degree of IOP fluctuations for as long as 12 months after surgical treatment with canaloplasty and trabeculotomy.

Canaloplasty and Trabeculotomy with the OMNI System in Pseudophakic Patients with Open-Angle Glaucoma: The ROMEO Study.

PURPOSE: Provide outcomes up to 12 months postsurgically for sequential canaloplasty and trabeculotomy with the OMNI surgical system (Sight Sciences, Inc) in pseudophakic patients with mild to moderate open-angle glaucoma. DESIGN: Retrospective, multicenter, single-arm study conducted at 10 multi-subspecialty ophthalmology practices and surgery centers located in 7 states (Arkansas, California, Kansas, Louisiana, Missouri, New York, and Texas). PARTICIPANTS: Eligible patients were pseudophakic, with mild/moderate open-angle glaucoma, 12-month follow-up, and medicated intraocular pressure (IOP) ≤36 mmHg on ≤4 medications preoperatively. One eye per patient was enrolled. METHODS: Institutional Review Board approved. All available cases meeting eligibility criteria were enrolled. Analysis of secondary end points was stratified by baseline (BL) IOP (>18 mmHg in group 1 and ≤18 mmHg in group 2) recognizing that treatment goals differed depending on BL IOP. MAIN OUTCOME MEASURES: Primary success was defined as the proportion of patients with ≥20% reduction in IOP from BL or IOP between 6 and 18 mmHg (inclusive) and on the same or fewer medications without secondary surgical intervention (SSI). Other effectiveness end points included mean IOP and number of medications at 12 months. Safety end points were best-corrected visual acuity (BCVA), adverse events (AEs), and SSIs. RESULTS: Forty-eight patients were enrolled, 24 in each group. Primary success was met by 73%. Mean IOP was reduced in group 1 (21.8 to 15.6 mmHg, P < 0.0001) and remained controlled in group 2 (15.4 to 13.9 mmHg, P = 0.24). Medications went from 1.7 ± 1.3 to 1.2 ± 1.3 (P = 0.024) in group 1 and from 2.0 ± 1.3 to 1.3 ± 1.3 (P = 0.003) in group 2. Adverse events were typical for the patient population undergoing angle surgery. Those reasonably related to the procedure were mild inflammation (13%), IOP spikes (6%), hyphema, corneal edema, and BCVA loss (all 4%). Five patients (10%) required an SSI. CONCLUSIONS: The sequential combination of canaloplasty followed by trabeculotomy performed as stand-alone procedures using the OMNI system in pseudophakic patients with open-angle glaucoma provides effective IOP reduction or sustained IOP control and meaningful medication reduction for up to 12 months postoperatively.

Canaloplasty and trabeculotomy ab interno with the OMNI system combined with cataract surgery in open-angle glaucoma: 12-month outcomes from the ROMEO study.

PURPOSE: To provide safety and effectiveness outcomes 12 months postsurgically for sequential canaloplasty and trabeculotomy with the OMNI system combined with cataract surgery in mild-to-moderate open-angle glaucoma (OAG). SETTING: Eleven ophthalmology practices and surgery centers located in 8 U.S. states. DESIGN: Retrospective, multicenter, single arm. METHODS: Twelve surgeons contributed 81 patients meeting eligibility criteria: OAG, 12-month follow-up, and medicated intraocular pressure (IOP) 36 mm Hg or less on 4 or less medications preoperatively. Analysis was stratified by baseline IOP: more than 18 mm Hg (Group 1) and 18 mm Hg (Group 2) or less. Success was defined as proportion with 20% reduction or greater in IOP or IOP between 6 and 18 mm Hg (inclusive) and on the same or fewer medications without secondary surgical intervention (SSI). Other endpoints included mean IOP and medications at 12 months. Safety included corrected distance visual acuity and adverse events (AEs). RESULTS: Of the 81 patients included, primary success was met by 79% in Group 1 and 81% in Group 2. The mean IOP was reduced in Group 1 (21.9 to 15.1 mm Hg, P < .0001) and remained controlled in Group 2 (14.1 to 13.4 mm Hg, P = .3177). Medications went from 2.0 ± 1.3 to 1.1 ± 1.1 in Group 1 and from 1.6 ± 1.3 to 0.9 ± 1.2 in Group 2. AEs were typical for cataract or angle surgery: mild inflammation (11%), IOP spikes (5%), and hyphema (4%). Four patients (5%) required an SSI. CONCLUSIONS: The OMNI system provided effective IOP reduction, sustained IOP control, and meaningful medication reduction for up to 12 months postoperative.

Circumferential Viscodilation Ab Interno Combined with Phacoemulsification for Treatment of Open-Angle Glaucoma: 12-Month Outcomes.

PURPOSE: To evaluate reduction in intraocular pressure (IOP) and medications for open-angle glaucoma (OAG) patients 12 months post-ab-interno circumferential viscodilation (VISCO360, Sight Sciences, Menlo Park, CA) in conjunction with cataract surgery. SETTING: Surgical center (New York, United States). DESIGN: Retrospective study of all OAG patients treated with 360-degree ab-interno viscodilation with cataract surgery by a single surgeon (NR) having 12 months of follow-up. Eyes were stratified by baseline IOP. Group 1: ≥18 mmHg (n=111). Group 2: <18 mmHg (n=69). METHODS: IOP was measured using Goldmann applanation tonometry. Medications, the number of medication-free eyes in each group at 12 months, and adverse events (AE) are reported. Analysis includes descriptive statistics and t-tests evaluating change from baseline. RESULTS: Groups 1 and 2 had mean baseline IOP of 22 and 14.3 mmHg. Medication use was 0.9 and 1.1 for Groups 1 and 2. At 12 months IOP for Group 1 was reduced 22% to 17.2 mmHg (p<0.0001) on 1.0 medications (p=0.7). IOP for Group 2 was similar to baseline (15.4 mmHg) but with a reduction in medications to 0.6 (p<0.05). The proportion medication free at 12 months was 32% and 47% for Groups 1 and 2 versus 34% and 26% at baseline, respectively. There were few AE (hyphema 1.7%, IOP elevation >10 mmHg >30 days post-op 1.1%, mild inflammation <1%) and no secondary surgical interventions excepting a single paracentesis, one-day postoperative. DISCUSSION: Treatment goals for the two groups differed. Pressure reduction (Group 1) or medication reduction (Group 2). Viscodilation achieved significant IOP reduction in Group 1 and medication reduction in Group 2 with many patients (both groups) medication free at 12 months. AE were infrequent and transient. CONCLUSION: Circumferential ab-interno viscodilation can be combined with cataract surgery and provide an IOP lowering and medication reduction benefit sustained for at least 12 months, for many patients with OAG.

Circumferential canal surgery: a brief history.

PURPOSE OF REVIEW: Most microinvasive glaucoma surgery (MIGS) procedures bypass outflow resistance residing proximally in the trabecular meshwork and inner wall of Schlemm's canal. A novel procedure combining trabeculotomy with viscodilation adds to this by also addressing distal resistance of the canal and collector channel ostia. This review examines the development and evidence for both trabeculotomy and canaloplasty separately and the combination in a single procedure. RECENT FINDINGS: Recent aqueous angiography studies have confirmed the segmental nature of outflow through Schlemm's canal highlighting the need to address distal outflow pathway resistance. Combined trabeculotomy and viscodilation ab interno is a novel approach with a new purpose-designed device (OMNI Surgical System) becoming available to surgeons in early 2018. Recent results as both a standalone and combined with cataract procedure demonstrate significant intraocular pressure reductions with an average 41% reduction from baseline in the pseudophakic group. SUMMARY: Targeting both distal as well as proximal points of outflow resistance in the conventional pathway may prove to be a highly efficacious MIGS modality. Additional large prospective studies are currently ongoing to confirm these preliminary results.

Clinical Outcomes for Diabetic Foot Ulcers Treated with Clostridial Collagenase Ointment or with a Product Containing Silver.

Objective: To compare outcomes of diabetic foot ulcers (DFUs) treated with clostridial collagenase ointment (CCO) or silver-containing products, both in combination with sharp debridement as needed. Approach: One hundred two subjects with qualifying DFUs were randomized to daily treatment with either CCO or a silver-containing product for 6 weeks followed by a 4 -week follow-up period. The primary outcome was the mean percent reduction in DFU area. A secondary outcome was the incidence of ulcer infections between groups. Results: At the end of treatment, the mean percent reduction in area from baseline of DFUs treated with CCO was 62% (p < 0.0001) and with silver was 40% (p < 0.0001). The difference between groups-22%-was not statistically significant (p = 0.071). Among ulcers closed by the end of treatment, the mean time to closure was 31.1 ± 9.0 days versus 37.1 ± 7.7 days, respectively (not statistically significant). There was a numerically greater incidence of target ulcer infections in the silver group (11, 21.6%) than in the CCO group (5, 9.8%; p = 0.208). No clinically relevant safety signals were identified in either group. Innovation: CCO treatment can progress a wound toward closure. Ulcer infection prophylaxis may not be sacrificed when treating DFU with CCO in lieu of silver-containing products. Conclusion: Both CCO and silver-containing products promote significant reduction in DFU area over 6 weeks of treatment with no clinically relevant safety concerns. Mean percent reduction in lesion area was numerically (22%) but not significantly greater with CCO compared to silver, as was time to ulcer closure, with an incidence of ulcer infection at least as low as for silver-containing products.

Supraciliary Microstent in Refractory Open-Angle Glaucoma: Two-Year Outcomes from the DUETTE Trial.

PURPOSE: The aim of the study was to report longer term (24-month) outcomes for primary open-angle glaucoma (POAG) patients refractory to medical therapy implanted with a supraciliary microstent (CyPass Micro-Stent, Alcon) in the DUETTE clinical study. METHODS: Sixty-five eyes were enrolled in this multicenter single-arm trial. Enrolled patients had POAG and intraocular pressure (IOP) >21 mmHg at baseline on 1-4 ocular hypotensive medications. Microstent implantation was performed as stand-alone surgery in these phakic or pseudophakic patients through a standard clear corneal approach. IOP and the use of IOP-lowering medications were monitored in this 1-year extension beyond the 12-month primary endpoint. RESULTS: Two-year follow-up visits were scheduled to confirm the 12-month results; safety data were obtained for 37 eyes of 35 patients. IOP at the end of the 24-month follow-up was 16.8 mmHg (n = 32), with a mean reduction of 7.7 mmHg from the baseline IOP of 24.5 mmHg (n = 65). Medication use was decreased from an average of 2.1 (baseline) to 1.5 at 24 months. The IOP and medication use at 24 months were consistent with the 12-month results (16.4 mmHg, 1.4 medications) reported previously. The adverse event profile remained as described for the first 12 months postimplantation. CONCLUSIONS: Placement of a supraciliary microstent provides up to 24 months of effective IOP lowering for medication-refractory POAG patients while, on average, decreasing the requirement for ocular hypotensive medications.

The Role of Minimally Invasive Glaucoma Surgery Devices in the Management of Glaucoma.

SIGNIFICANCE: Noncompliance is a problem affecting glaucoma patients. Approaches to improve adherence include the use of drug-delivery systems and safer forms of surgery. Minimally invasive glaucoma surgery (MIGS) has reduced complications, particularly in combination with cataract surgery, and with its good intraocular pressure (IOP) reduction may reduce or eliminate glaucoma medications.Glaucoma is a progressive disease and a leading cause of irreversible blindness. Elevated IOP is the most important risk factor, but effective medical management is dependent on patient adherence. This review summarizes the adherence problem in glaucoma and the efforts, including MIGS, to provide effective IOP control that is not dependent on patient compliance.The current understanding of patient adherence to pharmacological treatment of glaucoma is discussed including the challenges facing glaucoma patients. Historical approaches to providing IOP control in a sustained and reliable way are presented culminating in a review of the burgeoning use of MIGS devices.It is estimated that, in the United States, 27% of prescriptions written, across all medications, are not filled or are filled but not taken. For ocular hypotensive medications, even when filled, a large percentage (which varies widely by study) are not instilled as prescribed. To address this problem, methods for sustained drug delivery have been and continue to be developed, as well as surgical and laser approaches. Most recently, MIGS devices have gained popularity because of the ease of implantation during cataract surgery, favorable safety profile, and the possibility for effective and long-lasting IOP lowering, as well as the reduction or elimination of need for IOP-lowering medication.Poor adherence to treatment is relatively common among glaucoma patients and is associated with progression of disease. Recommending MIGS implantation during cataract surgery may offer optometrists a valuable treatment option in managing glaucoma patients, particularly where good adherence is in doubt.

Baseline factors affecting closure of venous leg ulcers.

OBJECTIVE: The objective of this study was to characterize factors associated with closure of venous leg ulcers (VLUs) in a pooled analysis of subjects from three randomized clinical trials. METHODS: Closure of VLUs after treatment with HP802-247, an allogeneic living cell therapy consisting of growth-arrested human keratinocytes and fibroblasts, vs standard therapy with compression bandaging was evaluated in three phase 3 clinical trials of similar design. Two trials enrolled subjects with VLUs ranging from 2 cm2 to 12 cm2 in area with 12-week treatment periods; the third trial enrolled subjects with VLUs between >12 cm2 and ≤36 cm2 with a 16-week treatment period. The first trial went to completion but failed to demonstrate a benefit to therapy with HP802-247 compared with placebo, and because of this, the remaining trials were terminated before completion. On the basis of no differences in outcomes between groups, subjects from both HP802-247 and control groups were pooled across all three studies. Cox proportional hazards regression analysis was employed to evaluate factors associated with VLU closure. RESULTS: This analysis included data from 716 subjects with VLU. Factors evaluated for association with healing included age, gender, race, diabetes, glycated hemoglobin level, body mass index, treatment (HP802-247 vs compression alone), and ulcer characteristics including location and area and duration at baseline. In an initial model including all of these putative factors, the following were significant at the P < .10 level: diagnosis of diabetes mellitus, gender, wound location (ankle or leg), baseline wound area, and wound duration at baseline. In a final model including only these factors, all but diabetes mellitus were significant at the P < .05 level. Effect sizes were as follows (hazard ratio [95% confidence interval]): female gender (1.384 [1.134-1.690]), wound location on the leg (1.490 [1.187-1.871]), smaller wound area at baseline (0.907 [0.887-0.927]), and shorter wound duration at baseline (0.971 [0.955-0.987]). CONCLUSIONS: Factors associated with VLU lesions including location, area, and duration were important predictors of healing. Women were more likely than men to achieve wound closure. Factors including body mass index, the presence of diabetes mellitus, and higher concentrations of glycated hemoglobin were not significant independent predictors of wound closure in this analysis.