Glaucoma: now and beyond.

The glaucomas are a group of conditions leading to irreversible sight loss and characterised by progressive loss of retinal ganglion cells. Although not always elevated, intraocular pressure is the only modifiable risk factor demonstrated by large clinical trials. It remains the leading cause of irreversible blindness, but timely treatment to lower intraocular pressure is effective at slowing the rate of vision loss from glaucoma. Methods for lowering intraocular pressure include laser treatments, topical medications, and surgery. Although modern surgical innovations aim to be less invasive, many have been introduced with little supporting evidence from randomised controlled trials. Many cases remain undiagnosed until the advanced stages of disease due to the limitations of screening and poor access to opportunistic case finding. Future research aims to generate evidence for intraocular pressure-independent neuroprotective treatments, personalised treatment through genetic risk profiling, and exploration of potential advanced cellular and gene therapies.

The Impact of Baseline Intraocular Pressure on Initial Treatment Response in the LiGHT Trial: Selective Laser Trabeculoplasty versus Medication.

PURPOSE: The Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial demonstrated the efficacy and safety of selective laser trabeculoplasty (SLT) compared to topical hypotensive medication as 1st-line therapy for ocular hypertension and open angle glaucoma. This sub-study explores the impact of pre-treatment (baseline) intraocular pressure (IOP) on treatment response for SLT and medication. DESIGN: Post hoc analysis of randomised control trial data. PARTICIPANTS: 1146 eyes from 662 patients were included in this analysis: 559 eyes in the SLT group and 587 in the medication group. METHODS: IOP reduction at 8 weeks following treatment with either SLT or prostaglandin analogue (PGA) eye drop initiation was assessed at different levels of baseline IOP, and the groups were compared. Differences in absolute and percentage IOP lowering between SLT and PGA medication were tested with a linear mixed effects model. Differences in the probability of achieving ≥20% IOP lowering between SLT and PGA medication, at different levels of baseline IOP, was estimated using a logistic mixed effects model. MAIN OUTCOME MEASURE: IOP lowering response to SLT versus PGA eye drops. RESULTS: Mean IOP was not significantly different between the groups, at baseline or 8 weeks following treatment initiation. Both treatments showed greater IOP lowering at higher baseline IOP and less IOP lowering at lower baseline IOP. SLT tended to achieve more IOP lowering than PGA drops at higher baseline IOP. PGA drops performed better at lower baseline IOP, and the difference compared to SLT, in terms of percentage IOP reduction, was significant at baseline IOP ≤ 17 mmHg. There was a significant difference in the relationship between baseline IOP and probability of ≥20% IOP lowering between the two treatments (p = 0.01), with SLT being more successful than PGA at baseline IOP > 22.51 mmHg. CONCLUSIONS: These data confirm previous reports of greater IOP lowering with higher baseline IOP for both SLT and topical hypotensive medication. In treatment naïve eyes, at higher baseline IOP, SLT was more successful at achieving ≥20% IOP lowering than PGA drops. At lower baseline IOP, a statistically greater percentage, but not absolute, IOP lowering was seen with PGA drops compared to SLT, although the clinical significance of this is uncertain.

Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial: Six-Year Results of Primary Selective Laser Trabeculoplasty versus Eye Drops for the Treatment of Glaucoma and Ocular Hypertension.

PURPOSE: The Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial has shown selective laser trabeculoplasty (SLT) to be clinically and cost-effective as a primary treatment of open-angle glaucoma (OAG) and ocular hypertension (OHT) at 3 years. This article reports health-related quality of life (HRQoL) and clinical effectiveness of initial treatment with SLT compared with intraocular pressure (IOP)-lowering eye drops after 6 years of treatment. DESIGN: Prospective, multicenter randomized controlled trial. PARTICIPANTS: Treatment-naive eyes with OAG or OHT initially treated with SLT or IOP-lowering drops. METHODS: Patients were allocated randomly to initial SLT or eye drops. After the initial 3 years of the trial, patients in the SLT arm were permitted a third SLT if necessary; patients in the drops arm were allowed SLT as a treatment switch or escalation. This study is registered at controlled-trials.com (identifier, ISRCTN32038223). MAIN OUTCOME MEASURES: The primary outcome was HRQoL at 6 years; secondary outcomes were clinical effectiveness and adverse events. RESULTS: Of the 692 patients completing 3 years in the LiGHT Trial, 633 patients (91.5%) entered the extension, and 524 patients completed 6 years in the trial (82.8% of those entering the extension phase). At 6 years, no significant differences were found for the EuroQol EQ-5D 5 Levels, Glaucoma Utility Index, and Glaucoma Quality of Life-15 (P > 0.05 for all). The SLT arm showed better Glaucoma Symptom Scale scores than the drops arm (83.6 ± 18.1 vs. 81.3 ± 17.3, respectively). Of eyes in the SLT arm, 69.8% remained at or less than the target IOP without the need for medical or surgical treatment. More eyes in the drops arm exhibited disease progression (26.8% vs. 19.6%, respectively; P = 0.006). Trabeculectomy was required in 32 eyes in the drops arm compared with 13 eyes in the SLT arm (P < 0.001); more cataract surgeries occurred in the drops arm (95 compared with 57 eyes; P = 0.03). No serious laser-related adverse events occurred. CONCLUSIONS: Selective laser trabeculoplasty is a safe treatment for OAG and OHT, providing better long-term disease control than initial drop therapy, with reduced need for incisional glaucoma and cataract surgery over 6 years.

Iridotomy to slow progression of visual field loss in angle-closure glaucoma.

BACKGROUND: Primary angle-closure glaucoma is a type of glaucoma associated with a physically obstructed anterior chamber angle. For example, contact between the iris and lens at the pupillary margin creates a pupillary block that increases resistance to aqueous outflow. Obstruction of the anterior chamber angle blocks drainage of fluids (aqueous humor) within the eye and may raise intraocular pressure (IOP). Elevated IOP is associated with glaucomatous optic nerve damage and visual field loss. Laser peripheral iridotomy ('iridotomy') is a procedure to eliminate pupillary block by allowing aqueous humor to pass directly from the posterior to anterior chamber, which is achieved by creating a hole in the iris using laser. Iridotomy is used to treat patients with primary angle-closure glaucoma, patients with primary angle-closure (narrow angles and no signs of glaucomatous optic neuropathy), and patients who are primary angle-closure suspects (patients with reversible obstruction). However, the effectiveness of iridotomy on slowing progression of visual field loss is uncertain. OBJECTIVES: To assess the effects of iridotomy compared with no iridotomy for primary angle-closure glaucoma, primary angle-closure, and primary angle-closure suspect. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 10), which contains the Cochrane Eyes and Vision Trials Register; MEDLINE Ovid; Embase Ovid; PubMed; LILACS; ClinicalTrials.gov; and the WHO ICTRP. The date of the most recent search was 10 October 2021. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials that compared iridotomy with no iridotomy in primary angle-closure suspects, people with primary angle-closure, or people with primary angle-closure glaucoma in one or both eyes were eligible. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and assessed the certainty of the body of evidence for prespecified outcomes using the GRADE approach. MAIN RESULTS: We identified four studies (3086 eyes of 1543 participants) that compared iridotomy with no iridotomy in participants (range of mean age 59.6 to 62.9 years) who were primary angle-closure suspects from China, Singapore, or the UK. Study investigators randomized one eye of each participant to iridotomy and the other to no iridotomy. Two studies provided long-term (five or more years) results. We judged the certainty of the evidence as moderate to low across the prespecified outcomes, downgrading for high risk of bias (e.g. performance and detection biases) and imprecision of results. Meta-analyses of data from two studies suggest that iridotomy probably results in little to no difference in IOP compared with no iridotomy at one year (mean difference (MD) 0.04 mm Hg, 95% confidence interval (CI) -0.17 to 0.24; I2 = 65%; 2598 eyes of 1299 participants; moderate certainty evidence) and five years (MD 0.12 mm Hg, 95% CI -0.11 to 0.35; I2 = 0%; 2016 eyes of 1008 participants), and in best-corrected visual acuity measured as logMAR at one year (MD 0.00, 95% CI -0.01 to 0.01; I2 = 69%; 2596 eyes of 1298 participants; moderate certainty evidence) and five years (MD 0.01, 95% CI -0.01 to 0.03; I2 = 0%; 2002 eyes of 1001 participants). In terms of gonioscopic findings, eyes treated with iridotomy likely had wider angles in Shaffer grading scale (MD 4.93 units, 95% CI 4.73 to 5.12; I2 = 59%; 2598 eyes of 1299 participants at one year; MD 5.07, 95% CI 4.78 to 5.36; I2 = 97%; 2016 eyes of 1008 participants at five years; moderate certainty evidence) and experienced fewer peripheral anterior synechiae (PAS) than eyes that received no iridotomy at five years (risk ratio (RR) 0.41, 95% CI 0.24 to 0.67; I2 = 28%; 2 studies, 2738 eyes of 1369 participants), but the evidence was less conclusive at one year (RR 0.62, 95% CI 0.25 to 1.54; I2 = 57%; 3 studies, 2896 eyes of 1448 participants; low certainty evidence). No studies reported data on the proportion of participants with progressive visual field loss during follow-up (the primary outcome of this review), mean number of medications to control IOP, or quality of life outcomes. Low certainty evidence suggests that iridotomy may result in little to no difference in the incidence of acute angle-closure (RR 0.29, 95% CI 0.07 to 1.20; I2 = 0%; 3 studies, 3006 eyes of 1503 participants). Other ocular adverse events (e.g. eye pain, dry eye, redness of eyes, and ocular discomfort), although rare, were more common in eyes treated with iridotomy than in eyes in the control group.  AUTHORS' CONCLUSIONS: We did not find sufficient evidence to draw any meaningful conclusions on the use of iridotomy for the purpose of slowing progression of visual field loss. No study reported on progressive visual field loss, the primary outcome of this review. Although there is moderate certainty evidence that iridotomy results in improved gonioscopic findings, in is unclear if these findings translate to clinically meaningful benefits.

Long-term Outcomes from the HORIZON Randomized Trial for a Schlemm's Canal Microstent in Combination Cataract and Glaucoma Surgery.

PURPOSE: To present the 5-year results of the HORIZON trial comparing cataract surgery (CS) combined with an intracanalicular microstent with CS alone. DESIGN: Prospective, multicenter, controlled randomized clinical trial. PARTICIPANTS: Patients with cataract and primary open-angle glaucoma treated with 1 or more glaucoma medications, washed-out diurnal intraocular pressure (DIOP) of 22 to 34 mmHg, and no prior incisional glaucoma surgery. METHODS: Eyes were randomized 2:1 to receive a Hydrus Microstent (HMS; Ivantis, Inc) or no stent after successful CS. MAIN OUTCOME MEASURES: Intraocular pressure (IOP), glaucoma medication use, repeat glaucoma surgery, visual acuity, visual field, procedure-related adverse events, and corneal endothelial cell counts. RESULTS: Three hundred sixty-nine eyes were randomized to HMS treatment, and 187 eyes were randomized to CS only. Study groups were well matched for preoperative IOP, medication use, washed-out DIOP, and glaucoma severity. Five-year follow-up was completed in 80% of patients. At 5 years, the HMS group included a higher proportion of eyes with IOP of 18 mmHg or less without medications than the CS group (49.5% vs. 33.8%; P = 0.003), as well as a greater likelihood of IOP reduction of 20% or more without medications than the CS group (54.2% vs. 32.8%; P < 0.001). The number of glaucoma medications was 0.5 ± 0.9 in the HMS group and 0.9 ± 0.9 in the CS group (P < 0.001), and 66% of eyes in the HMS group were medication free compared with 46% in the CS group (P < 0.001). The cumulative risk of incisional glaucoma surgery was lower in the HMS group (2.4% vs. 6.2%; P = 0.027, log-rank test). No clinical or statistically significant differences were found in the rate of endothelial cell loss from 3 to 60 months between the HMS and CS alone groups (P = 0.261). CONCLUSIONS: The addition of a Schlemm's canal microstent in conjunction with CS was safe, resulted in lowered IOP and medication use, and reduced the need for postoperative incisional glaucoma filtration surgery compared with CS after 5 years. Long-term presence of the implant did not affect the corneal endothelium adversely.

Three-Year Findings of the HORIZON Trial: A Schlemm Canal Microstent for Pressure Reduction in Primary Open-Angle Glaucoma and Cataract.

PURPOSE: To report 3-year outcomes of the HORIZON study comparing cataract surgery (CS) with Hydrus Microstent (Ivantis, Inc) implantation versus CS alone. DESIGN: Multicenter randomized clinical trial. PARTICIPANTS: Five hundred fifty-six eyes from 556 patients with cataract and primary open-angle glaucoma (POAG) treated with 1 or more glaucoma medication, washed out diurnal intraocular pressure (IOP) of 22 to 34 mmHg, and no prior incisional glaucoma surgery. METHODS: After phacoemulsification, eyes were randomized 2:1 to receive a Hydrus Microstent or no stent. Follow-up included comprehensive eye examinations through 3 years. MAIN OUTCOME MEASURES: Outcome measures included IOP, medical therapy, reoperation rates, visual acuity, adverse events, and changes in corneal endothelial cell counts. RESULTS: Three hundred sixty-nine eyes were randomized to microstent treatment and 187 to CS only. Preoperative IOP, medication use, washed-out diurnal IOP, and glaucoma severity did not differ between the two treatment groups. At 3 years, IOP was 16.7 ± 3.1 mmHg in the microstent group and 17.0 ± 3.4 mmHg in the CS group (P = 0.85). The number of glaucoma medications was 0.4 ± 0.8 in the microstent group and 0.8 ± 1.0 in the CS group (P < 0.001), and 73% of microstent group eyes were medication free compared with 48% in the CS group (P < 0.001). The microstent group included a higher proportion of eyes with IOP of 18 mmHg or less without medications compared with the CS group (56.2% vs. 34.6%; P < 0.001), as well as IOP reduction of at least 20%, 30%, or 40% compared with CS alone. The cumulative probability of incisional glaucoma surgery was lower in the microstent group (0.6% vs. 3.9%; hazard ratio, 0.156; 95% confidence interval, 0.031-0.773; P = 0.020). No difference was found in postoperative corneal endothelial cell loss between groups. No procedure- or device-related serious adverse events resulting in vision loss occurred in either group. CONCLUSIONS: Combined CS and microstent placement for mild to moderate POAG is safe, more effective in lowering IOP with fewer medications, and less likely to result in further incisional glaucoma filtration surgery than CS alone at 3 years.

Ab interno supraciliary microstent surgery for open-angle glaucoma.

BACKGROUND: Glaucoma is the leading cause of global irreversible blindness, often associated with raised intraocular pressure (IOP). Where medical or laser treatment has failed or is not tolerated, surgery is often required. Minimally-invasive surgical approaches have been developed in recent years to reduce IOP with lower surgical risks. Supraciliary microstent surgery for the treatment of open-angle glaucoma (OAG) is one such approach. OBJECTIVES: To evaluate the efficacy and safety of supraciliary microstent surgery for the treatment of OAG, and to compare with standard medical, laser or surgical treatments. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2020, Issue 8); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 27 August 2020. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) of supraciliary microstent surgery, alone or with cataract surgery, compared to other surgical treatments (cataract surgery alone, other minimally invasive glaucoma device techniques, trabeculectomy), laser treatment or medical treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts from the database search to identify studies that met the selection criteria. Data extraction, analysis, and evaluation of risk of bias from selected studies was performed independently and according to standard Cochrane methodology. MAIN RESULTS: One study met the inclusion criteria of this review, evaluating the efficacy and safety of the Cypass supraciliary microstent surgery for the treatment of OAG, comparing phacoemulsification + supraciliary microstent surgery with phacoemulsification alone over 24 months. This study comprised 505 eyes of 505 participants with both OAG and cataract, 374 randomised to the phacoemulsification + microstent group.  In this study, the perceived risk of bias from random sequence generation, allocation concealment and selective reporting was low. However, we considered the study to be at high risk of performance bias as surgeons/investigators were unmasked. Attrition bias was unclear, with 448/505 participants contributing to per protocol analysis. Insertion of a Cypass supraciliary microstent combined with phacoemulsification probably increases the proportion of participants who are medication-free (not using eye-drops) at 24 months compared with phacoemulsification alone (85% versus 59%, risk ratio (RR) 1.27, 95% confidence interval (CI) 1.09 to 1.49, moderate-certainty evidence). There is high-certainty evidence that a greater improvement in mean IOP occurs in the phacoemulsification + microstent group - mean (SD) change in IOP from baseline of -5.4 (3.9) mmHg in the phacoemulsification group, compared to -7.4 (4.4) mmHg in the phacoemulsification + microstent group at 24 months (mean difference -2.0 mmHg, 95% CI -2.85 to -1.15). There is moderate-certainty evidence that insertion of a microstent is probably associated with a greater reduction in use of IOP-lowering drops (mean reduction of 0.7 medications in the phacoemulsification group, compared to a mean reduction of 1.2 medications in the phacoemulsification + microstent group). Insertion of a microstent during phacoemulsification may reduce the requirement for further glaucoma intervention to control IOP at a later stage compared to phacoemulsification alone (RR 0.26, 95% CI 0.07 to 1.04, low-certainty evidence). There is no evidence relating to the rate of visual field progression, or proportion of participants whose visual field loss progressed in this study. There is moderate-certainty evidence showing little or no difference in the proportion of participants experiencing postoperative complications over 24 months between participants in the microstent group compared to those who received phacoemulsification alone (RR 1.1, 95% CI 0.8 to 1.4). Five year post-approval data regarding the safety of the Cypass supraciliary microstent showed increased endothelial cell loss, associated with the position of the microstent in the anterior chamber. There were no reported health-related quality of life (HRQoL) outcomes in the included study. AUTHORS' CONCLUSIONS: Data from this single RCT show superiority of supraciliary microstent surgery when combined with phacoemulsification compared to phacoemulsification alone in achieving medication-free control of OAG. However, there are long-term safety concerns with the device used in this trial, relating to the observed significant loss of corneal endothelial cells at five years following device implantation. At the time of this review, this device has been withdrawn from the market. This review has found that few high-quality studies exist comparing supraciliary microstent surgery to standard medical, laser or surgical glaucoma treatments. This should be addressed by further appropriately designed RCTs with sufficient long-term follow-up to ensure robust safety data are obtained. Consideration of health-related quality of life outcomes should also feature in trial design.

Ab interno trabecular bypass surgery with Trabectome for open-angle glaucoma.

BACKGROUND: Glaucoma is the leading cause of irreversible blindness. Minimally invasive surgical techniques, such as ab interno trabecular bypass surgery, have been introduced to prevent glaucoma from progressing.   OBJECTIVES: In light of the potential benefits for people with open-angle glaucoma and the widespread uptake of the technique, it is important to critically evaluate the evidence for whether treatment with ab interno trabecular bypass surgery with Trabectome is both efficacious and safe. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2020, Issue 7); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 17 July 2020. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) of ab interno trabecular bypass surgery with Trabectome compared to other surgical treatments (other minimally invasive glaucoma device techniques, trabeculectomy), laser treatment, or medical treatment. We also included trials in which these devices were combined with phacoemulsification compared to phacoemulsification in combination with other glaucoma surgery or alone. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcome was proportion of participants who were medication-free (not using eye drops). Secondary outcomes included mean change in intraocular pressure (IOP), proportion of participants who required further glaucoma surgery, mean change in quality of life, proportion of participants who achieved an IOP of 21 mmHg or less, 17 mmHg or less, or 14 mmHg or less and rate of visual field progression. Adverse effects were the proportion of participants experiencing intra- and postoperative complications. All outcomes were measured in the short term (6 to 18 months), medium term (18 to 36 months), and long term (36 months or longer). MAIN RESULTS: In this update, we included one RCT which had previously been identified as an ongoing study in our 2016 publication. This trial was a single-centre, single-surgeon RCT set in Canada with 19 participants. Participants were adults who had open-angle glaucoma, open angles, and had inadequately controlled IOP that required surgical intervention. The study was terminated before the intended sample size was reached 'due to slow recruitment and increasing lack of clinical equipoise over time'. This reduced the power of the study to detect clinically important effects. We assessed the trial as being at high risk of attrition, reporting, and other potential sources of biases. The risks of performance and detection bias are unclear. The intervention group of 10 people had Trabectome ab interno trabeculotomy combined with cataract extraction (phaco-AIT) and the comparator group of 9 people had trabeculectomy with mitomycin C combined with cataract extraction (phaco-Trab), one of whom was lost to follow-up. Seven of 10 participants in the phaco-AIT group and 4 of 8 in the phaco-Trab group were medication-free (not using drops) at 12 months (odds ratio (OR) 2.33, 95% confidence interval (CI) 0.34 to 16.2; very low-certainty evidence). At 12 months, the mean change in IOP was worse for phaco-AIT than for phaco-Trab, but this evidence was very uncertain (mean difference (MD) 3.70 mmHg, 95% CI -1.44 to 8.84; very low-certainty evidence) in the phaco-AIT group, as was the difference in the mean number of IOP-lowering drops taken per day (MD -0.41, 95% CI -1.22 to 0.40; very low-certainty evidence). Only one participant in the phaco-AIT group required further glaucoma surgery. The study protocol declared that quality of life and visual field progression were measured, but they were not reported All 8 participants with complete data in the phaco-Trab group and 8 of 10 in the phaco-AIT had at least one early or late postoperative complication (e.g. day 1 IOP spike, hypotony, choroidal effusion, bleb leak or encapsulation, uveitis, or peripheral anterior synechiae). The evidence was very low-certainty due to high risk of bias for several domains for this study and for large imprecision of all estimates. We also identified one ongoing study, identified from the International Clinical Trials Registry Platform (ICTRP): a multicentre, open, RCT comparing Trabectome to ab interno trabeculectomy using microhook. The study investigators plan to recruit 120 adults between 20 and 90 years of age. The primary outcome is duration of treatment success. Secondary outcomes include postoperative IOP, number of anti-glaucoma medications, and adverse events. AUTHORS' CONCLUSIONS: There is currently no high-quality evidence for the outcomes of ab interno trabecular bypass surgery with Trabectome for open-angle glaucoma. Properly designed RCTs are needed to assess the long-term efficacy and safety of this technique.

Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial.

BACKGROUND: Primary open angle glaucoma and ocular hypertension are habitually treated with eye drops that lower intraocular pressure. Selective laser trabeculoplasty is a safe alternative but is rarely used as first-line treatment. We compared the two. METHODS: In this observer-masked, randomised controlled trial treatment-naive patients with open angle glaucoma or ocular hypertension and no ocular comorbidities were recruited between 2012 and 2014 at six UK hospitals. They were randomly allocated (web-based randomisation) to initial selective laser trabeculoplasty or to eye drops. An objective target intraocular pressure was set according to glaucoma severity. The primary outcome was health-related quality of life (HRQoL) at 3 years (assessed by EQ-5D). Secondary outcomes were cost and cost-effectiveness, disease-specific HRQoL, clinical effectiveness, and safety. Analysis was by intention to treat. This study is registered at controlled-trials.com (ISRCTN32038223). FINDINGS: Of 718 patients enrolled, 356 were randomised to the selective laser trabeculoplasty and 362 to the eye drops group. 652 (91%) returned the primary outcome questionnaire at 36 months. Average EQ-5D score was 0·89 (SD 0·18) in the selective laser trabeculoplasty group versus 0·90 (SD 0·16) in the eye drops group, with no significant difference (difference 0·01, 95% CI -0·01 to 0·03; p=0·23). At 36 months, 74·2% (95% CI 69·3-78·6) of patients in the selective laser trabeculoplasty group required no drops to maintain intraocular pressure at target. Eyes of patients in the selective laser trabeculoplasty group were within target intracoluar pressure at more visits (93·0%) than in the eye drops group (91·3%), with glaucoma surgery to lower intraocular pressure required in none versus 11 patients. Over 36 months, from an ophthalmology cost perspective, there was a 97% probability of selective laser trabeculoplasty as first treatment being more cost-effective than eye drops first at a willingness to pay of £20 000 per quality-adjusted life-year gained. INTERPRETATION: Selective laser trabeculoplasty should be offered as a first-line treatment for open angle glaucoma and ocular hypertension, supporting a change in clinical practice. FUNDING: National Institute for Health Research, Health and Technology Assessment Programme.

Visual Field Outcomes from the Multicenter, Randomized Controlled Laser in Glaucoma and Ocular Hypertension Trial (LiGHT).

PURPOSE: To compare visual field outcomes of ocular hypertensive and glaucoma patients treated first with medical therapy with those treated first with selective laser trabeculoplasty (SLT). DESIGN: Secondary analysis of patients from the Laser in Glaucoma and Ocular Hypertension study, a multicenter randomized controlled trial. PARTICIPANTS: Three hundred forty-four patients (588 eyes) treated first with medical therapy and 344 patients (590 eyes) treated first with SLT. METHODS: Visual fields (VFs) were measured using standard automated perimetry and arranged in series (median length and duration, 9 VFs over 48 months). Hierarchical linear models were used to estimate pointwise VF progression rates, which were then averaged to produce a global progression estimate for each eye. Proportions of points and patients in each treatment group with fast (<-1 dB/year) or moderate (<-0.5 dB/year) progression were compared using log-binomial regression. MAIN OUTCOME MEASURES: Pointwise and global progression rates of total deviation (TD) and pattern deviation (PD). RESULTS: A greater proportion of eyes underwent moderate or fast TD progression in the medical therapy group compared with the SLT group (26.2% vs. 16.9%; risk ratio [RR], 1.55; 95% confidence interval [CI], 1.23-1.93; P < 0.001). A similar pattern was observed for pointwise rates (medical therapy, 26.1% vs. SLT, 19.0%; RR, 1.37; 95% CI, 1.33-1.42; P < 0.001). A greater proportion of pointwise PD rates were categorized as moderate or fast in the medical therapy group (medical therapy, 11.5% vs. SLT, 8.3%; RR, 1.39; 95% CI, 1.32-1.46; P < 0.001). No statistical difference was found in the proportion of eyes that underwent moderate or fast PD progression (medical therapy, 9.9% vs. SLT, 7.1%; RR, 1.39; 95% CI, 0.95, 2.03; P = 0.0928). CONCLUSIONS: A slightly larger proportion of ocular hypertensive and glaucoma patients treated first with medical therapy underwent rapid VF progression compared with those treated first with SLT.

Efficacy of Repeat Selective Laser Trabeculoplasty in Medication-Naive Open-Angle Glaucoma and Ocular Hypertension during the LiGHT Trial.

PURPOSE: To determine the efficacy of repeat selective laser trabeculoplasty (SLT) in medication-naive open-angle glaucoma (OAG) and ocular hypertensive (OHT) patients requiring repeat treatment for early to medium-term failure during the Laser in Glaucoma and Ocular Hypertension (LiGHT) trial. DESIGN: Post hoc analysis of SLT treatment arm of a multicenter prospective randomized controlled trial. PARTICIPANTS: Treatment-naive OAG or OHT requiring repeat 360-degree SLT within 18 months. Retreatment was triggered by predefined IOP and disease-progression criteria (using objective individualized target IOPs). METHODS: After SLT at baseline, patients were followed for a minimum of 18 months after second (repeat) SLT. A mixed-model analysis was performed with the eye as the unit of analysis, with crossed random effects to adjust for correlation between fellow eyes and repeated measures within eyes. Kaplan-Meier curves plot the duration of effect. MAIN OUTCOME MEASURES: Initial (early) IOP lowering at 2 months and duration of effect after initial and repeat SLT. RESULTS: A total of 115 eyes of 90 patients received repeat SLT during the first 18 months of the trial. Pretreatment IOP before initial SLT was significantly higher than before retreatment IOP of repeat SLT (mean difference, 3.4 mmHg; 95% confidence interval [CI], 2.6-4.3 mmHg; P < 0.001). Absolute IOP reduction at 2 months was greater after initial SLT compared with repeat SLT (mean difference, 1.0 mmHg; 95% CI, 0.2-1.8 mmHg; P = 0.02). Adjusted absolute IOP reduction at 2 months (adjusting for IOP before initial or repeat laser) was greater after repeat SLT (adjusted mean difference, -1.1 mmHg, 95% CI, -1.7 to -0.5 mmHg; P = 0.001). A total of 34 eyes were early failures (retreatment 2 months after initial SLT) versus 81 later failures (retreatment >2 months after initial SLT). No significant difference in early absolute IOP reduction at 2 months after repeat SLT was noted between early and later failures (mean difference, 0.3 mmHg; 95% CI, -1.1 to 1.8 mmHg; P = 0.655). Repeat SLT maintained drop-free IOP control in 67% of 115 eyes at 18 months, with no clinically relevant adverse events. CONCLUSIONS: These exploratory analyses demonstrate that repeat SLT can maintain IOP at or below target IOP in medication-naive OAG and OHT eyes requiring retreatment with at least an equivalent duration of effect to initial laser.

Ab interno trabecular bypass surgery with Schlemm´s canal microstent (Hydrus) for open angle glaucoma.

BACKGROUND: Glaucoma is a leading cause of irreversible blindness. A number of minimally-invasive surgical techniques have been introduced as a treatment to prevent glaucoma from progressing; ab interno trabecular bypass surgery with the Schlemm's canal Hydrus microstent is one of them. OBJECTIVES: To evaluate the efficacy and safety of ab interno trabecular bypass surgery with the Hydrus microstent in treating people with open angle glaucoma (OAG). SEARCH METHODS: On 7 May 2019, we searched CENTRAL (2019, Issue 5), which contains the Cochrane Eyes and Vision Trials Register; Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov; and the WHO ICTRP. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) of the Hydrus microstent, alone or with cataract surgery, compared to other surgical treatments (cataract surgery alone, other minimally-invasive glaucoma device techniques, trabeculectomy), laser treatment, or medical treatment. DATA COLLECTION AND ANALYSIS: A minimum of three authors independently extracted data from reports of included studies, using a data collection form and analysed data, based on standard Cochrane methods. MAIN RESULTS: We included three published studies, with 808 people randomised. Two studies had multiple international recruitment centres in the USA and other countries. The third study had several sites based in Europe. All three studies were sponsored by the Hydrus manufacturer Ivantis Inc. All studies included participants with mainly mild or moderate OAG (mean deviation between -3.6 dB (decibel) and -8.4 dB in all study arms), which was controlled with medication in many participants (mean medicated intraocular pressure (IOP) 17.9 mmHg to 19.1 mmHg). There were no concerns regarding allocation concealment bias, but masking of outcome assessors was high or unclear risk in all studies; masking of participants was achieved, and losses to follow-up were not a concern. Two studies compared the Hydrus microstent combined with cataract surgery to cataract surgery alone, in participants with visually significant cataracts and OAG. We found moderate-certainty evidence that adding the Hydrus microstent to cataract surgery increased the proportion of participants who were medication-free from about half to more than three quarters at 12-month, short-term follow-up (risk ratio (RR) 1.59, 95% confidence interval (CI) 1.39 to 1.83; 2 studies, 639 participants; I² = 0%; and 24-month, medium-term follow-up (RR 1.63, 95% CI 1.40 to 1.88; 2 studies, 619 participants; I² = 0%). The Hydrus microstent combined with cataract surgery reduced the medium-term mean change in unmedicated IOP (after washout) by 2 mmHg more compared to cataract surgery alone (mean difference (MD) -2.00, 95% CI -2.69 to -1.31; 2 studies, 619 participants; I² = 0%; moderate-certainty evidence), and the mean change in IOP-lowering drops (MD -0.41, 95% CI -0.56 to -0.27; 2 studies, 619 participants; I² = 0%; low-certainty evidence). We also found low-certainty evidence that adding a Hydrus microstent to cataract surgery reduced the need for secondary glaucoma surgery from about 2.5% to less than 1% (RR 0.17, 95% CI 0.03 to 0.86; 2 studies, 653 participants; I² = 27%; low-certainty evidence). Intraocular bleeding, loss of 2 or more visual acuity (VA) lines, and IOP spikes of 10 mmHg or more were rare in both groups; estimates were imprecise, and included both beneficial and harmful effects. There were no cases of endophthalmitis in either group. No data were available on the proportion of participants achieving IOP less than 21 mmHg, 17 mmHg, or 14 mmHg; health-related quality of life (HRQOL), or visual field progression. One study provided short-term data for the Hydrus microstent compared with the iStent trabecular micro-bypass stent (iStent: implantation of two devices in a single procedure) in 152 participants with OAG (148 in analyses). Use of the Hydrus increased the proportion of medication-free participants from about a quarter to about half compared to those who received iStent, but this estimate was imprecise (RR 1.94, 95% CI 1.21 to 3.11; low-certainty evidence). Use of the Hydrus microstent reduced unmedicated IOP (after washout) by about 3 mmHg more than the iStent (MD -3.10, 95% CI -4.17 to -2.03; moderate-certainty evidence), and the use of IOP-lowering medication (MD -0.60, 95% CI -0.99 to -0.21; low-certainty evidence). Both devices achieved a final IOP < 21 mmHg in most participants (Hydrus microstent: 91.8%; iStent: 84%; RR 1.09, 95% CI 0.97 to 1.23; low-certainty evidence). None of the participants who received the Hydrus microstent (N = 74) required additional glaucoma surgery; two participants who received the iStent (N = 76) did. Few adverse events were found in either group. No data were available on the proportion of participants achieving IOP less than 17 mmHg or 14 mmHg, or on HRQOL. AUTHORS' CONCLUSIONS: In people with cataracts and generally mild to moderate OAG, there is moderate-certainty evidence that the Hydrus microstent with cataract surgery compared to cataract surgery alone, likely increases the proportion of participants who do not require IOP lowering medication, and may further reduce IOP at short- and medium-term follow-up. There is moderate-certainty evidence that the Hydrus microstent is probably more effective than the iStent in lowering IOP of people with OAG in the short-term. Few studies were available on the effects of the Hydrus microstent, therefore the results of this review may not be applicable to all people with OAG, particularly in selected people with medically uncontrolled glaucoma, since IOP was controlled with medication in many participants in the included studies. Complications may be rare using the Hydrus microstent, as well as the comparator iStent, but larger studies are needed to investigate its safety.

Primary Selective Laser Trabeculoplasty for Open-Angle Glaucoma and Ocular Hypertension: Clinical Outcomes, Predictors of Success, and Safety from the Laser in Glaucoma and Ocular Hypertension Trial.

PURPOSE: To report clinical efficacy, predictors of success, and safety of primary selective laser trabeculoplasty (SLT) used in treatment-naive patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). DESIGN: Post hoc analysis of a multicenter, prospective, randomized, controlled trial. PARTICIPANTS: Treatment-naive patients with OAG or OHT. METHODS: Patients randomized to SLT or topical medication and treated to predefined target intraocular pressures (IOPs) requiring ≥20% IOP reduction from baseline for all disease severity levels. OUTCOME MEASURES: Initial (early) absolute IOP-lowering at 2 months. Achievement of drop-free disease-control: meeting target IOP without disease progression or need for additional topical medication over 36 months after SLT. Predictors of early absolute IOP-lowering and drop-free disease-control after single initial SLT. Frequency of laser-related complications. RESULTS: A total of 611 eyes (195 OHT and 416 OAG) of 355 patients received SLT, and 622 eyes (185 OHT and 437 OAG) of 362 patients received topical medication at baseline. Early absolute IOP-lowering after SLT was no different between OHT and OAG eyes (adjusted mean difference = -0.05 mmHg; 95% confidence interval [CI], -0.6 to 0.5 mmHg; P = 0.85). No difference was noted in early absolute IOP-lowering between topical medication and primary SLT (adjusted mean difference = -0.1 mmHg; 95% CI, -0.6 to 0.4 mmHg; P = 0.67). Early absolute IOP-lowering with primary SLT was positively associated with baseline IOP (coefficient 0.58; 95% CI, 0.53-0.63; P < 0.001) and negatively with female gender (coefficient -0.63; 95% CI, -1.23 to -0.02; P = 0.04). At 36 months, 536 eyes (87.7% of 611 eyes) of 314 patients (88.5% of 355 patients) were available for analysis. Some 74.6% of eyes (400 eyes) treated with primary SLT achieved drop-free disease-control at 36 months; 58.2% (312 eyes) after single SLT. Total SLT power and 2-month IOP were predictors of drop-free disease-control at 36 months after single SLT. Six eyes of 6 patients experienced immediate post-laser IOP spike (>5 mmHg from pretreatment IOP) with 1 eye requiring treatment. CONCLUSIONS: Primary SLT achieved comparable early absolute IOP-lowering in OHT versus OAG eyes. Drop-free disease-control was achieved in approximately 75% eyes at 36 months after 1 or 2 SLTs, the majority of these after single SLT. These analyses are exploratory but support primary SLT to be effective and safe in treatment-naive OAG and OHT eyes.

Endoscopic cyclophotocoagulation (ECP) for open angle glaucoma and primary angle closure.

BACKGROUND: Glaucoma is a leading cause of irreversible blindness. A number of minimally invasive surgical techniques have been introduced as a treatment to prevent glaucoma progressing. Among them, endoscopic cyclophotocoagulation (ECP) is a cyclodestructive procedure developed by Martin Uram in 1992. OBJECTIVES: To evaluate the efficacy and safety of ECP in people with open angle glaucoma (OAG) and primary angle closure whose condition is inadequately controlled with drops. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 6); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 12 July 2018. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) of ECP compared to other surgical treatments (other minimally invasive glaucoma device techniques, trabeculectomy), laser treatment or medical treatment. We also planned to include trials where these devices were combined with phacoemulsification compared to phacoemulsification alone. DATA COLLECTION AND ANALYSIS: Two review authors planned to independently extract data from reports of included studies using a data collection form and analyse data based on methods expected by Cochrane. Our primary outcome was proportion of participants who were drop-free (not using eye drops). Secondary outcomes included mean change in IOP; proportion of participants who achieved an IOP of 21 mmHg or less, 17 mmHg or less or 14 mmHg or less; and proportion of participants experiencing intra- and postoperative complications, We planned to measure all outcomes in the short-term (six to 18 months), medium-term (18 to 36 months), and long-term (36 months onwards). MAIN RESULTS: We found one ongoing study that met our inclusion criteria (ChiCTR-TRC-14004233). The study compares combined phacoemulsification with ECP to phacoemulsification alone in people with primary angle closure glaucoma. The primary outcome is intraocular pressure (IOP) and number of IOP-lowering drugs. A total of 50 people have been enrolled. The study started in February 2014 and the trialists have completed recruitment and are in the process of collecting data. AUTHORS' CONCLUSIONS: There is currently no high-quality evidence for the effects of ECP for OAG and primary angle closure. Properly designed RCTs are needed to assess the medium and long-term efficacy and safety of this technique.

Iridotomy to slow progression of visual field loss in angle-closure glaucoma.

BACKGROUND: Primary angle-closure glaucoma is a type of glaucoma associated with a physically obstructed anterior chamber angle. Obstruction of the anterior chamber angle blocks drainage of fluids (aqueous humor) within the eye and may raise intraocular pressure (IOP). Elevated IOP is associated with glaucomatous optic nerve damage and visual field loss. Laser peripheral iridotomy (often just called 'iridotomy') is a procedure to eliminate pupillary block by allowing aqueous humor to pass directly from the posterior to anterior chamber through use of a laser to create a hole in the iris. It is commonly used to treat patients with primary angle-closure glaucoma, patients with primary angle closure (narrow angles and no signs of glaucomatous optic neuropathy), and patients who are primary angle-closure suspects (patients with reversible obstruction). The effectiveness of iridotomy on slowing progression of visual field loss, however, is uncertain. OBJECTIVES: To assess the effects of iridotomy compared with no iridotomy for primary angle-closure glaucoma, primary angle closure, and primary angle-closure suspects. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 9) which contains the Cochrane Eyes and Vision Trials Register; MEDLINE Ovid; Embase Ovid; PubMed; LILACS; ClinicalTrials.gov; and the ICTRP. The date of the search was 18 October 2017. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials that compared iridotomy to no iridotomy in primary angle-closure suspects, patients with primary angle closure, or patients with primary angle-closure glaucoma in one or both eyes were eligible. DATA COLLECTION AND ANALYSIS: Two authors worked independently to extract data on study characteristics, outcomes for the review, and risk of bias in the included studies. We resolved differences through discussion. MAIN RESULTS: We identified two trials (2502 eyes of 1251 participants) that compared iridotomy to no iridotomy. Both trials recruited primary angle suspects from Asia and randomized one eye of each participant to iridotomy and the other to no iridotomy. Because the full trial reports are not yet available for both trials, no data are available to assess the effectiveness of iridotomy on slowing progression of visual field loss, change in IOP, need for additional surgeries, number of medications needed to control IOP, mean change in best-corrected visual acuity, and quality of life. Based on currently reported data, one trial showed evidence that iridotomy increases angle width at 18 months (by 12.70°, 95% confidence interval (CI) 12.06° to 13.34°, involving 1550 eyes, moderate-certainty evidence) and may be associated with IOP spikes at one hour after treatment (risk ratio 24.00 (95% CI 7.60 to 75.83), involving 1468 eyes, low-certainty evidence). The risk of bias of the two studies was overall unclear due to lack of availability of a full trial report. AUTHORS' CONCLUSIONS: The available studies that directly compared iridotomy to no iridotomy have not yet published full trial reports. At present, we cannot draw reliable conclusions based on randomized controlled trials as to whether iridotomy slows progression of visual field loss at one year compared to no iridotomy. Full publication of the results from the studies may clarify the benefits of iridotomy.

Iridotomy to slow progression of angle-closure glaucoma.

This is the protocol for a review and there is no abstract. The objectives are as follows: The primary objective is to assess the role of iridotomy-compared with observation-in the prevention of visual field loss for individuals who have primary angle closure or primary angle-closure glaucoma in at least one eye. We will also examine the role of iridotomy in the prevention of elevated intraocular pressure (IOP) in individuals with narrow angles (primary angle-closure suspect) in at least one eye.

Ab interno trabecular bypass surgery with Trabectome for open angle glaucoma.

BACKGROUND: Glaucoma is the leading cause of irreversible blindness. Minimally invasive surgical techniques, such as ab interno trabecular bypass surgery, have been introduced to prevent glaucoma progressing. OBJECTIVES: The main objective was to assess the results at two years of ab interno trabecular bypass surgery with Trabectome for open angle glaucoma in comparison to conventional medical, laser, or surgical treatment in terms of efficacy and safety. A secondary objective was to examine the effects of Trabectome surgery in people who have concomitant phacoemulsification in comparison to those who do not have concomitant phacoemulsification. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 4), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to May 2016), EMBASE (January 1980 to May 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 12 May 2016. SELECTION CRITERIA: We included only randomised controlled trials (RCTs) of ab interno trabecular bypass surgery with Trabectome. DATA COLLECTION AND ANALYSIS: We planned to have two review authors independently extract data from reports of included studies using a data collection form. MAIN RESULTS: One randomised controlled trial identified from ClinicalTrials.gov, NCT00901108, met the criteria for inclusion. This study has subsequently been terminated. The ClinicalTrials.gov record indicates that the investigators plan to complete 12 months of follow-up and analysis on 19 participants already recruited into the trial. AUTHORS' CONCLUSIONS: There is currently no high-quality evidence for the outcomes of ab interno trabecular bypass surgery with Trabectome for open angle glaucoma. Properly designed RCTs are needed to assess the long-term efficacy and safety of this technique.

Priorities for health outcomes in glaucoma in an ethnically diverse UK cohort: an observational study.

OBJECTIVES: To assess whether patients from minority ethnic groups have different perceptions about the quality-of-life outcomes that matter most to them. DESIGN: Cross-sectional observational study. SETTING: High volume eye centres serving the most ethnically diverse region in the UK, recruiting from July 2021 to February 2022. PARTICIPANTS: 511 patients with primary open-angle glaucoma and the predisease state of ocular hypertension. MAIN OUTCOME MEASURES: The main outcome was participants' self-reported priorities for health outcomes. RESULTS: Participants fell into one of four clusters with differing priorities for health outcomes, namely: (1) vision, (2) drop freedom, (3) intraocular pressure and (4) one-time treatment. Ethnicity was the strongest determinant of cluster membership after adjusting for potential confounders. Compared with white patients prioritising vision alone, the OR for black/black British patients was 7.31 (95% CI 3.43 to 15.57, p<0.001) for prioritising drop freedom; 5.95 (2.91 to 12.16, p<0.001) for intraocular pressure; and 2.99 (1.44 to 6.18, p=0.003) for one-time treatment. For Asian/Asian British patients, the OR was 3.17 (1.12 to 8.96, p=0.030) for prioritising intraocular pressure as highly as vision. Other ethnic minority groups also had higher ORs for prioritising health outcomes other than vision alone: 4.50 (1.03 to 19.63, p=0.045) for drop freedom and 5.37 (1.47 to 19.60, p=0.011) for intraocular pressure. CONCLUSIONS: Ethnicity is strongly associated with differing perceptions about the health outcomes that matter. An individualised and ethnically inclusive approach is needed when selecting and evaluating treatments in clinical and research settings.

Finding Ophthalmic Risk and Evaluating the Value of Eye exams and their predictive Reliability (FOREVER)-A cohort study in a Danish high street optician setting: Design and methodology.

PURPOSE: The purpose of the study was to describe the rationale and design of Project FOREVER (Finding Ophthalmic Risk and Evaluating the Value of Eye exams and their predictive Reliability). DESIGN: Project FOREVER will build a comprehensive database of clinical eye and vision data collected from ~280 000 adults at 100 optician stores across Denmark. The FOREVER database (FOREVERdb) includes detailed data from refraction, visual acuity, intraocular pressure, corneal thickness, visual field assessments and retinal fundus images. Linkage to the comprehensive Danish national registries with, that is diagnostic and prescribing data permits investigation of rare associations and risk factors. 30 000 individuals over 50 also provide a saliva sample for later genetic studies and blood pressure measurements. Of these 30 000, 10 000 will also get optical coherence tomography (OCT) nerve and retinal scans. This subpopulation data is reviewed by ophthalmologists for disease detection. All participants will be asked to complete a questionnaire assessing lifestyle, self-perceived eye health and general health. Enrolment of participants began in April 2022. PERSPECTIVE: The FOREVERdb is a powerful tool to answer a wide range of research questions that can pave the way for better eye health. This database will provide valuable insights for future studies investigating the correlations between eye and general health in a Danish population cohort, enabling research to identify potential risk factors for a range of diseases.