Effectiveness of Netarsudil versus Brimonidine in Eyes already Being Treated with Glaucoma Medications at a Single Academic Tertiary Care Practice: A Comparative Study.

Background: Rho kinase inhibitors, such as netarsudil, are a relatively new class of medications recently introduced into the market for the treatment of glaucoma, the leading cause of irreversible blindness in the world. Previous clinical trials have studied netarsudil's efficacy when used as a first- or second-line agent but limited studies have investigated its effectiveness in the real world where it is more commonly used as a third, fourth, or fifth agent in combination with other topical medications. Equally important, prior studies have not compared its effectiveness to its peer medications in these settings. Objective: To compare intraocular pressure (IOP) lowering after initiation of netarsudil or brimonidine therapy in patients with glaucoma using >2 medications for IOP management. Methods: A chart review of 369 eyes from 279 patients followed at a single academic tertiary practice was performed with an institutional review board waiver of consent to compare IOP lowering after prescription of netarsudil (n = 176) versus brimonidine (n = 193) as a third, fourth, or fifth IOP-lowering agent. Patients were identified by querying the electronic medical record for those with a glaucoma-related diagnosis who were prescribed either medication. Five sequential IOP measurements were obtained to determine the mean change in IOP before and after treatment (ΔIOP = mean IOP4,5 - mean IOP1,2,3). A multilevel linear mixed-effects model assessed the influence of medication (independent variable) on ΔIOP (dependent variable). Additional independent variables of interest included the number of glaucoma medications at baseline, age, sex, glaucoma type and severity, race, and pretreatment IOP. Bootstrap analysis was performed to remove sampling bias and confirm mixed-effects model findings. Kaplan-Meier survival analysis evaluated the probability of requiring additional intervention within 3 years following the date of medication prescription. Results: The unadjusted mean (SD) ΔIOP for netarsudil and brimonidine was -2.20 (4.11) mm Hg and -2.21 (3.25) mm Hg, respectively (P = 0.484). The adjusted linear mixed-effects models and bootstrap analysis demonstrated that there was no statistical difference in IOP-lowering effectiveness between the medications. Netarsudil and brimonidine failed to adequately control IOP at similar rates with 42% and 47% probabilities of survival respectively by the 3-year follow-up (P = 0.520). Conclusions: When escalating pharmacologic therapy, the IOP-lowering effect of netarsudil appeared to be similar to that produced by brimonidine. (Curr Ther Res Clin Exp. 2023; 84:XXX-XXX).

Pharmacologic interventions for mydriasis in cataract surgery.

BACKGROUND: Cataract surgery is one of the most common surgical procedures performed worldwide. Achieving appropriate intraoperative mydriasis is one of the critical factors associated with the safety and performance of the surgery. Inadequate pupillary dilation or constriction of the pupil during cataract surgery can impair the surgeon's field of view and make it difficult to maneuver instruments. OBJECTIVES: To evaluate the relative effectiveness of achieving pupillary dilation during phacoemulsification for cataract extraction using three methods of pupillary dilation: topical mydriatics, intracameral mydriatics, or depot delivery systems. We also planned to document and compare the risk of intraoperative and postoperative complications following phacoemulsification for cataract extraction, as well as the cost-effectiveness of these methods for pupillary dilation. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Trials Register) (2021, Issue 1); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 22 January 2021. SELECTION CRITERIA: We included only randomized controlled trial (RCTs) in which participants underwent phacoemulsification for cataract extraction. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. MAIN RESULTS: We included a total of 14 RCTs (1670 eyes of 1652 participants) in this review. Of the 14 trials, 7 compared topical versus intracameral mydriatics, 6 compared topical mydriatics versus depot delivery systems, and 1 compared all three methods. We were unable to calculate overall estimates of comparative effectiveness for most outcomes due to statistical heterogeneity among the estimates from individual studies or because outcome data were available from only a single study. Furthermore, the certainty of evidence for most outcomes was low or very low, due primarily to imprecision and risk of bias. Comparison 1: topical mydriatics versus intracameral mydriatics Four RCTs (739 participants, 757 eyes) of the 8 RCTs that had compared these two methods reported mean pupillary diameters at the time surgeons had performed capsulorhexis; all favored topical mydriatics, but heterogeneity was high (I2 = 95%). After omitting 1 RCT that used a paired-eyes design, evidence from three RCTs (721 participants and eyes) suggests that mean pupil diameter at the time of capsulorhexis may be greater with topical mydriatics than with intracameral mydriatics, but the evidence is of low certainty (mean difference 1.06 mm, 95% confidence interval (CI) 0.81 mm to 1.31 mm; I2 = 49%). Four RCTs (224 participants, 242 eyes) reported mean pupillary diameter at the beginning of cataract surgery; the effect estimates from all trials favored topical mydriatics, with very low-certainty evidence. Five RCTs (799 participants, 817 eyes) reported mean pupillary diameter at the end of cataract surgery. Data for this outcome from the largest RCT (549 participants and eyes) provided evidence of a small difference in favor of intracameral mydriasis. On the other hand, 2 small RCTs (78 participants, 96 eyes) favored topical mydriatics, and the remaining 2 RCTs (172 participants) found no meaningful difference between the two methods, with very low-certainty evidence. Five RCTs (799 participants, 817 eyes) reported total intraoperative surgical time. The largest RCT (549 participants and eyes) reported decreased total intraoperative time with intracameral mydriatics, whereas 1 RCT (18 participants, 36 eyes) favored topical mydriatics, and the remaining 3 RCTs (232 participants) found no difference between the two methods, with very low-certainty evidence. Comparison 2: topical mydriatics versus depot delivery systems Of the 7 RCTs that compared these two methods, none reported mean pupillary diameter at the time surgeons performed capsulorhexis. Six RCTs (434 participants) reported mean pupillary diameter at the beginning of cataract surgery. After omitting 1 RCT suspected to be responsible for high heterogeneity (I2 = 80%), meta-analysis of the other 5 RCTs (324 participants and eyes) found no evidence of a meaningful difference between the two methods, with very low-certainty evidence. Three RCTs (210 participants) reported mean pupillary diameter at the end of cataract surgery, with high heterogeneity among effect estimates for this outcome. Estimates of mean differences and confidence intervals from these three RCTs were consistent with no difference between the two methods. A fourth RCT reported only means for this outcome, with low-certainty evidence. Two small RCTs (118 participants) reported total intraoperative time. Surgical times were lower when depot delivery was used, but the confidence interval estimated from one trial was consistent with no difference, and only mean times were reported from the other trial, with very low-certainty evidence. Comparison 3: Intracameral mydriatics versus depot delivery systems Only one RCT (60 participants) compared intracameral mydriatics versus depot delivery system. Mean pupillary diameter at the time the surgeon performed capsulorhexis, phacoemulsification time, and cost outcomes were not reported. Mean pupil diameter at the beginning and end of cataract surgery favored the depot delivery system, with very low-certainty evidence. Adverse events Evidence from one RCT (555 participants and eyes) comparing topical mydriatics versus intracameral mydriatics suggests that ocular discomfort may be greater with topical mydriatics than with intracameral mydriatics at one week (risk ratio (RR) 10.57, 95% CI 1.37 to 81.34) and one month (RR 2.51, 95% CI 1.36 to 4.65) after cataract surgery, with moderate-certainty evidence at both time points. Another RCT (30 participants) reported iris-related complications in 11 participants in the intracameral mydriatics group versus no complications in the depot delivery system group, with very low-certainty evidence. Cardiovascular related adverse events were rarely mentioned. AUTHORS' CONCLUSIONS: Data from 14 completed RCTs were inadequate to establish the superiority of any of three methods to achieve mydriasis for cataract surgery, based on pupillary dilation at different times during the surgery or on time required for surgery. Only one trial had a sample size adequate to yield a robust effect estimate. Larger, well-designed trials are needed to provide robust estimates for the comparison of mydriasis approaches for beneficial and adverse effects.

Implementation of Novel Protocols in an Ophthalmic Ambulatory Surgical Center to Resume Surgical Procedures During COVID-19.

BACKGROUND AND OBJECTIVES: With the resumption of elective ophthalmic surgery during COVID-19, revised protocols were mandated to protect both staff and patients from transmission while increasing case numbers. We discuss a widely generalizable and in-depth protocol intended to safely allow the restart of elective procedures in 2 dedicated ophthalmic ambulatory surgical centers (ASCs) using monitored anesthesia care. METHODS: A single-center review of protocols and practices designed to limit COVID-19 transmission. RESULTS: All patients were tested within 72 hours prior to the procedure with a COVID-19 nasal swab to assess for active disease. A distance of 6 ft between each stretcher and the staff within the ASC was maintained when possible. Preoperative anesthetizing and dilating eye drops were administered from multiuse bottles without contact with surfaces. Surgical cases were restarted at a reduced capacity of a maximum of 7 per day to distance patient arrivals. Removal of waiting room chairs and the creation of new break areas allowed for social distancing. CONCLUSION: As recommendations change on the basis of an increased understanding of the COVID-19 virus, ophthalmologists and ASC staff need to tailor protocols and workflows to limit transmission of virus with resumption of ocular surgery.

Suicide Screening in Sturge-Weber Syndrome: An Important Issue in Need of Further Study.

BACKGROUND: Sturge-Weber syndrome is a neurocutaneous disorder associated with epilepsy, glaucoma, cognitive impairments, and a port-wine birthmark. Although individuals with Sturge-Weber syndrome are vulnerable to known risk factors for suicide, including chronic illness and physical differences (port-wine birthmark), frequency of suicidal ideation and attempts, and the clinical factors associated with suicide risk, in patients with Sturge-Weber syndrome is unknown. METHODS: As a part of routine hospital practice, all outpatients aged eight years and older underwent suicide risk screening during nursing triage using a standardized suicide screening tool. Suicide risk screening results, demographic variables, and medical history (as available) for patients with Sturge-Weber syndrome (N = 34; median age = 15.5; range = 8 to 47 years, 44% male) and other neurological conditions seen at the same institution (N = 369; median age = 14; range = 8 to 78 years, 66% male) were used for retrospective within- and between-group analysis. RESULTS: In the combined sample of Sturge-Weber syndrome and neurologically involved patients, a positive suicide risk screen was related to Sturge-Weber syndrome diagnosis (P = 0.043); analysis by sex showed increased risk of Sturge-Weber syndrome diagnosis in males (P = 0.008), but not in females. Within the Sturge-Weber syndrome group, use of a selective serotonin reuptake inhibitor (P = 0.019) was related to a positive risk screen. CONCLUSION: People with Sturge-Weber syndrome may be at greater risk of suicidal thoughts or behaviors than those with other neurological conditions. Further study of suicide risk in patients with Sturge-Weber syndrome is needed.

Intraocular Pressure Following Prerandomization Glaucoma Medication Washout in the HORIZON and COMPASS Trials.

PURPOSE: To assess the effectiveness of topical ocular hypotensive medications in patients with open-angle glaucoma and to identify factors associated with postwashout intraocular pressure (IOP) elevation. DESIGN: Secondary analysis of prerandomization data from 2 prospective, multicenter, randomized clinical trials. METHODS: Fourteen hundred subjects (1,400 eyes, 781 from the HORIZON study of the Hydrus micro-stent and 619 from the COMPASS study of the Cypass micro-stent) with primary open-angle glaucoma who were using 0-4 classes of topical IOP-lowering medication underwent Goldmann applanation tonometry before and after a protocol-defined washout period. RESULTS: The mean (standard deviation) age was 70.7 (8.0) years and 55.6% were female. The change in IOP following washout for patients using 0 (n = 100), 1 (n = 705), 2 (n = 355), 3 (n = 214), or 4 (n = 26) medications was 0.2 (2.8), 5.7 (3.3), 6.9 (3.7), 8.8 (5.0), and 9.5 (4.1) mm Hg, respectively (P < .001, Kruskal-Wallis test). Postwashout IOP change was similar between the HORIZON and COMPASS cohorts. No difference in postwashout IOP change was detected among individual prostaglandin analogues in patients on monotherapy. A generalized linear model identified the following factors to be associated with greater IOP rise upon medication washout: greater number of glaucoma medications, higher unmedicated IOP, thinner central corneal thickness (CCT), lack of prior selective laser trabeculoplasty (SLT), and male sex. CONCLUSIONS: Cessation of glaucoma medications results in a dose-dependent IOP increase in treated open-angle glaucoma patients. Two independent clinical trial cohorts exhibit similar levels of IOP elevation upon washout, using standardized methodology to estimate real-world medication effectiveness. Thicker CCT and history of SLT may predict reduced response to IOP lowering medications.

Alexandrite laser induced uveitis & pigment dispersion: A case report and review of the literature.

PURPOSE: To describe a complication of an upper eyelid alexandrite laser procedure. OBSERVATIONS: A 55-year-old woman presented with left eye blurred vision and photophobia after a left upper eyelid procedure with an alexandrite laser. She had elevated intraocular pressure (IOP), anterior chamber cell and pigment, posterior synechiae, and retroillumination defects in the left eye. She was treated with topical prednisolone and brimonidine. Six months later, although her anterior chamber had cleared and IOP had normalized, the patient reported decreased vision-related quality of life from persistent photophobia. CONCLUSIONS AND IMPORTANCE: Alexandrite lasers are commonly used for hair removal and skin depigmentation. When used periocularly without proper eye protection, they have the potential to create irreversible ocular complications. This case demonstrates the importance of proper eye protection with periocular laser procedures.

Effect of a Schlemm's Canal Microstent on Early Postoperative Intraocular Pressure after Cataract Surgery: An Analysis of the HORIZON Randomized Controlled Trial.

PURPOSE: To compare early postoperative intraocular pressure (IOP) in patients who underwent cataract surgery alone with those who underwent cataract surgery combined with implantation of a Hydrus Microstent (HMS) (Ivantis, Irvine, CA). DESIGN: Subanalysis of data from the randomized controlled HORIZON trial, a multicenter trial including 26 US and 12 international sites. PARTICIPANTS: Participants with mild/moderate primary open-angle glaucoma (POAG) and visually significant cataract with mean modified diurnal IOP between 22 and 34 mmHg after washout of IOP-lowering medications. METHODS: A total of 556 subjects were randomized in a 2:1 ratio to undergo cataract surgery with placement of the HMS versus cataract surgery alone (no microstent [NMS]). All eyes were washed out of IOP-lowering medications before surgery and remained unmedicated until surgery. No IOP-lowering prophylaxis was used postoperatively. Comprehensive eye examination including measurement of intraocular pressure was conducted on postoperative day (POD) 1, week 1, and month 1. MAIN OUTCOME MEASURES: Postoperative IOP >40 mmHg was analyzed as the primary outcome. Incidence of IOP increase >10 mmHg above baseline, unmedicated IOP, and mean IOP were analyzed as secondary outcomes. RESULTS: A total of 369 eyes were randomized to the HMS group, and 187 eyes were randomized to cataract surgery alone. The HMS and NMS groups did not differ with respect to baseline demographic or ocular characteristics. On POD1, the incidence of IOP spike >40 mmHg was significantly higher at 14.4% in the NMS group compared with 1.4% in the HMS group (P < 0.001). The incidence of IOP increase ≥10 mmHg relative to baseline on POD1 was also significantly higher in the NMS group than in the HMS group (22.5% vs. 3.0%, P < 0.001). IOP in the NMS group was significantly higher than in the HMS group (27.6 vs. 17.0 mmHg, P < 0.001). In multivariable logistic regression analysis, higher baseline IOP predicted higher odds of POD1 IOP spike >40 mmHg, whereas the presence of HMS was associated with a lower likelihood of postoperative IOP spike. CONCLUSIONS: The addition of an HMS at the time of cataract surgery lowered the risk of markedly elevated IOP in the early postoperative period in patients with glaucoma.

A Prospective Randomized Trial Comparing Hydrus and iStent Microinvasive Glaucoma Surgery Implants for Standalone Treatment of Open-Angle Glaucoma: The COMPARE Study.

PURPOSE: To compare the efficacy of different microinvasive glaucoma surgery (MIGS) devices for reducing intraocular pressure (IOP) and medications in open-angle glaucoma (OAG). DESIGN: Prospective, multicenter, randomized clinical trial. PARTICIPANTS: One hundred fifty-two eyes from 152 patients aged 45 to 84 years with OAG, Shaffer angle grade III-IV, best-corrected visual acuity (BCVA) 20/30 or better, and IOP 23 to 39 mmHg after washout of all hypotensive medications. Eyes with secondary glaucoma other than pseudoexfoliative or pigmentary glaucoma, angle closure, previous incisional glaucoma surgery, or any significant ocular pathology other than glaucoma were excluded. INTERVENTION: Study eyes were randomized 1:1 to standalone MIGS consisting of either 1 Hydrus Microstent (Ivantis, Inc, Irvine, CA) or 2 iStent Trabecular Micro Bypass devices (Glaukos Inc, San Clemente, CA). Follow-up was performed 1 day, 1 week, and 1, 3, 6, and 12 months postoperatively. MAIN OUTCOME MEASURES: Within-group and between-group differences in IOP and medications at 12 months and complete surgical success defined as freedom from repeat glaucoma surgery, IOP 18 mmHg or less, and no glaucoma medications. Safety measures included the frequency of surgical complications, changes in visual acuity, slit-lamp findings, and adverse events. RESULTS: Study groups were well matched for baseline demographics, glaucoma status, medication use, and baseline IOP. Twelve-month follow-up was completed in 148 of 152 randomized subjects (97.3%). At 12 months, the Hydrus had a greater rate of complete surgical success (P < 0.001) and reduced medication use (difference = -0.6 medications, P = 0.004). More Hydrus subjects were medication free at 12 months (difference = 22.6% P = 0.0057). Secondary glaucoma surgery was performed in 2 eyes in the 2-iStent group (3.9%) and in none of the Hydrus eyes. Two eyes in the Hydrus group and 1 in the 2-iStent group had BCVA loss of ≥2 lines. CONCLUSION: Standalone MIGS in OAG with the Hydrus resulted in a higher surgical success rate and fewer medications compared with the 2-iStent procedure. The 2 MIGS devices have similar safety profiles.

Outcomes of a Modified Trabeculectomy Closure Technique.

PRECIS: A modified closure for trabeculectomy in which the conjunctiva is incised posterior to the limbus and reapproximated using 2 nylon sutures, provided similar surgical outcomes to the standard trabeculectomy closure technique. PURPOSE: To examine the surgical outcomes of a modified trabeculectomy closure technique in which the conjunctiva is incised posterior to the limbus and reapproximated using 2 sutures, burying the posterior conjunctiva under an anterior lip of conjunctiva. MATERIALS AND METHODS: This retrospective review included 73 eyes that underwent trabeculectomies between 2015 and 2017 at Johns Hopkins Hospital by a single surgeon. We analyzed traditional closures used from January 2015 to May 2016, and modified closures used from July 2016 to March 2017. The main outcome measures were a reduction in intraocular pressure at 3, 6, and 12 months, reduction in the number of medications at 12 months, and total number of postoperative complications. RESULTS: There was no difference in reduction of intraocular pressure at 3 months (9.9±8.2 vs. 10.5±8.7 mm Hg), 6 months (10.8±9.6 vs. 10.6±8.3 mm Hg), or 12 months (12.2±8.9 vs. 10.0±9.3 mm Hg) in the standard (n=44) and modified groups (n=29), respectively. There was a similar reduction in the use of glaucoma medications in the standard group (1.2±1.5 vs. 1.0±1.1) compared with the modified group and no difference in the number of postoperative complications (25.0% vs. 17.2%, respectively) (P>0.05 for all). CONCLUSIONS: The modified closure provided similar results to the standard closure for trabeculectomy. Further studies are needed to determine whether the 2 techniques differ in surgical outcomes over a longer follow-up or other surgical parameters (eg, ease, surgical time, learning curve).

A Schlemm Canal Microstent for Intraocular Pressure Reduction in Primary Open-Angle Glaucoma and Cataract: The HORIZON Study.

OBJECTIVE: To compare cataract surgery with implantation of a Schlemm canal microstent with cataract surgery alone for the reduction of intraocular pressure (IOP) and medication use after 24 months. DESIGN: Prospective, multicenter, single-masked, randomized controlled trial. PARTICIPANTS: Subjects with concomitant primary open-angle glaucoma (POAG), visually significant cataract, and washed-out modified diurnal IOP (MDIOP) between 22 and 34 mmHg. METHODS: Subjects were randomized 2:1 to receive a single Hydrus Microstent (Ivantis, Inc, Irvine, CA) in the Schlemm canal or no stent after uncomplicated phacoemulsification. Comprehensive eye examinations were conducted 1 day, 1 week, and 1, 3, 6, 12, 18, and 24 months postoperatively. Medication washout and MDIOP measurement were repeated at 12 and 24 months. MAIN OUTCOME MEASURES: The primary and secondary effectiveness end points were the proportion of subjects demonstrating a 20% or greater reduction in unmedicated MDIOP and change in mean MDIOP from baseline at 24 months, respectively. Hypotensive medication use was tracked throughout the course of follow-up. Safety measures included the frequency of surgical complications and adverse events. RESULTS: A total of 369 eyes were randomized after phacoemulsification to Hydrus Microstent (HMS) and 187 to no microstent (NMS). At 24 months, unmedicated MDIOP was reduced by ≥20% in 77.3% of HMS group eyes and in 57.8% of NMS group eyes (difference = 19.5%, 95% confidence interval [CI] 11.2%-27.8%, P < 0.001). The mean reduction in 24-month unmedicated MDIOP was -7.6±4.1 mmHg (mean ± standard deviation) in the HMS group and -5.3±3.9 mmHg in the NMS group (difference = -2.3 mmHg; 95% CI, -3.0 to -1.6; P < 0.001). The mean number of medications was reduced from 1.7±0.9 at baseline to 0.3±0.8 at 24 months in the HMS group and from 1.7±0.9 to 0.7±0.9 in the NMS group (difference = -0.4 medications; P < 0.001). There were no serious ocular adverse events related to the microstent, and no significant differences in safety parameters between the 2 groups. CONCLUSIONS: This 24-month multicenter randomized controlled trial demonstrated superior reduction in MDIOP and medication use among subjects with mild-to-moderate POAG who received a Schlemm canal microstent combined with phacoemulsification compared with phacoemulsification alone.

A Systematic Evaluation of State Laws Governing Optometric Glaucoma Management in the United States Upto 2015.

PURPOSE: To describe state laws that govern the optometric practice of glaucoma management in the United States and to correlate those laws with state demographics upto 2015. MATERIALS AND METHODS: We performed a cross-sectional ecological study of the 50 United States and the District of Columbia. Regulations governing optometric scope of practice as written by each state Board of Optometry were reviewed. Specific optometric privileges assessed included: ability to manage glaucoma independently, use of diagnostic pharmaceutical agents, use of therapeutic pharmaceutical agents (including topical and oral steroids and other oral pharmaceutical agents), IV injections, intraocular injections, therapeutic lasers, presence of defined referral, and comanagement guidelines, and hours of yearly continuing education needed for glaucoma management. Optometric privilege was compared with demographic and employment information for each state. RESULTS: Optometrists in all states, except for Massachusetts, and the District of Columbia are allowed to manage glaucoma; 16 states have defined comanagement guidelines. Therapeutic lasers are allowed in 3 states: Kentucky, Louisiana, and Oklahoma. States with defined comanagement guidelines had a mean of 6.9±1.9 ophthalmologists per 100,000 people, significantly more than the 5.3±1.1 in states without defined comanagement of glaucoma (P<0.01). Binary logistic regression showed that, accounting for population and area, the higher the number of optometrists in a state, the less likely there is to be defined comanagement [ß (SE)=-0.008 (0.003), P=0.02] and the greater the number of ophthalmologists in a given state, the more likely a state has defined comanagement [ß (SE)=-0.13 (0.006)]. CONCLUSIONS: There is a diversity of regulations that govern optometric management of glaucoma in each of the 50 states and the District of Columbia. The number of optometrists and ophthalmologists in a state may influence state regulations governing optometric practice and referral guidelines.