Lens extraction versus laser peripheral iridotomy for acute primary angle closure.

BACKGROUND: Acute primary angle closure (APAC) is a potentially blinding condition. It is one of the few ophthalmic emergencies and carries high rates of visual morbidity in the absence of timely intervention. Laser peripheral iridotomy (LPI) has been the standard of care thus far. However, LPI does not eliminate the long-term risk of chronic angle closure glaucoma and other associated sequelae. There has been increasing interest in lens extraction as the primary treatment for the spectrum of primary angle closure disease, and it is as yet unclear whether these results can be extrapolated to APAC, and whether lens extraction provides better long-term outcomes. We therefore sought to evaluate the effectiveness of lens extraction in APAC to help inform the decision-making process.  OBJECTIVES: To assess the effect of lens extraction compared to LPI in the treatment of APAC. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 1), Ovid MEDLINE, Ovid MEDLINE E-pub Ahead of Print, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily (January 1946 to 10 January 2022), Embase (January 1947 to 10 January 2022), PubMed (1946 to 10 January 2022), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to 10 January 2022), 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. We last searched the electronic databases on 10 January 2022. SELECTION CRITERIA: We included randomized controlled clinical trials comparing lens extraction against LPI in adult participants ( ≥ 35 years) with APAC in one or both eyes. 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 included two studies conducted in Hong Kong and Singapore, comprising 99 eyes (99 participants) of predominantly Chinese origin. The two studies compared LPI with phacoemulsification performed by experienced surgeons. We assessed that both studies were at high risk of bias. There were no studies evaluating other types of lens extraction procedures.  Phacoemulsification may result in an increased proportion of participants with intraocular pressure (IOP) control compared with LPI at 18 to 24 months (risk ratio (RR) 1.66, 95% confidence interval (CI) 1.28 to 2.15; 2 studies, n = 97; low certainty evidence) and may reduce the need for further IOP-lowering surgery within 24 months (RR 0.07, 96% CI 0.01 to 0.51; 2 studies, n = 99; very low certainty evidence). Phacoemulsification may result in a lower mean IOP at 12 months compared to LPI (mean difference (MD) -3.20, 95% CI -4.79 to -1.61; 1 study, n = 62; low certainty evidence) and a slightly lower mean number of IOP-lowering medications at 18 months (MD -0.87, 95% CI -1.28 to -0.46; 1 study, n = 60; low certainty evidence), but this may not be clinically significant. Phacoemulsification may have little to no effect on the proportion of participants with one or more recurrent APAC episodes in the same eye (RR 0.32, 95% CI 0.01 to 7.30; 1 study, n = 37; very low certainty evidence). Phacoemulsification may result in a wider iridocorneal angle assessed by Shaffer grading at six months (MD 1.15, 95% CI 0.83 to 1.47; 1 study, n = 62; very low certainty evidence). Phacoemulsification may have little to no effect on logMAR best-corrected visual acuity (BCVA) at six months (MD -0.09, 95% CI -0.20 to 0.02; 2 studies, n = 94; very low certainty evidence). There was no evidence of a difference in the extent of peripheral anterior synechiae (PAS) (clock hours) between intervention arms at 6 months (MD -1.86, 95% CI -7.03 to 3.32; 2 studies, n = 94; very low certainty evidence), although the phacoemulsification group may have less PAS (degrees) at 12 months (MD -94.20, 95% CI -140.37 to -48.03; 1 study, n = 62) and 18 months (MD -127.30, 95% CI -168.91 to -85.69; 1 study, n = 60).  In one study, there were 26 adverse events in the phacoemulsification group: intraoperative corneal edema (n = 12), posterior capsular rupture (n = 1), intraoperative bleeding from iris root (n = 1), postoperative fibrinous anterior chamber reaction (n = 7), and visually significant posterior capsular opacification (n = 5), and no cases of suprachoroidal hemorrhage or endophthalmitis. There were four adverse events in the LPI group: closed iridotomy (n = 1) and small iridotomies that required supplementary laser (n = 3). In the other study, there was one adverse event in the phacoemulsification group (IOP > 30 mmHg on day 1 postoperatively (n = 1)), and no intraoperative complications. There were five adverse events in the LPI group: transient hemorrhage (n = 1), corneal burn (n = 1), and repeated LPI because of non-patency (n = 3).  Neither study reported health- or vision-related quality of life measures. AUTHORS' CONCLUSIONS: Low certainty evidence suggests that early lens extraction may produce more favorable outcomes compared to initial LPI in terms of IOP control. Evidence for other outcomes is less clear. Future high-quality and longer-term studies evaluating the effects of either intervention on the development of glaucomatous damage and visual field changes as well as health-related quality of life measures would be helpful.

The Singapore Asymptomatic Narrow Angles Laser Iridotomy Study: Five-Year Results of a Randomized Controlled Trial.

PURPOSE: To examine the efficacy of laser peripheral iridotomy (LPI) in patients who received a diagnosis of primary angle-closure suspect (PACS). DESIGN: Prospective, randomized controlled trial. PARTICIPANTS: This multicenter, randomized controlled trial (ClinicalTrials.gov identifier, NCT00347178) enrolled 480 patients older than 50 years from glaucoma clinics in Singapore with bilateral asymptomatic PACS (defined as having ≥2 quadrants of appositional angle closure on gonioscopy). METHODS: Each participant underwent prophylactic LPI in 1 randomly selected eye, whereas the fellow eye served as a control. Patients were followed up yearly for 5 years. MAIN OUTCOME MEASURES: The primary outcome measure was development of primary angle closure (PAC; defined as presence of peripheral anterior synechiae, intraocular pressure [IOP] of >21 mmHg, or both or acute angle closure [AAC]) or primary angle-closure glaucoma (PACG) over 5 years. RESULTS: Of the 480 randomized participants, most were Chinese (92.7%) and were women (75.8%) with mean age of 62.8 ± 6.9 years. Eyes treated with LPI reached the end point less frequently after 5 years (n = 24 [5.0%]; incidence rate [IR], 11.65 per 1000 eye-years) compared with control eyes (n = 45 [9.4%]; IR, 21.84 per 1000 eye-years; P = 0.001). The adjusted hazard ratio (HR) for progression to PAC was 0.55 (95% confidence interval [CI], 0.37-0.83; P = 0.004) in LPI-treated eyes compared with control eyes. Older participants (per year; HR, 1.06; 95% CI, 1.03-1.10; P < 0.001) and eyes with higher baseline IOP (per millimeter of mercury; HR, 1.35; 95% CI, 1.22-1.50; P < 0.0001) were more likely to reach an end point. The number needed to treat to prevent an end point was 22 (95% CI, 12.8-57.5). CONCLUSIONS: In patients with bilateral asymptomatic PACS, eyes that underwent prophylactic LPI reached significantly fewer end points compared with control eyes over 5 years. However, the overall incidence of PAC or PACG was low.

Outcomes of surgical bleb revision at a tertiary Singapore eye hospital.

PURPOSE: To describe the outcomes of surgical bleb revisions from a tertiary glaucoma service in Singapore. METHODS: One hundred and thirty-one eyes of 129 patients who underwent surgical bleb revisions at the Singapore National Eye Centre between 2007 and 2014 were included in the study. The indications for bleb revision were: bleb-related infection (BRI), early and late bleb leak, early and late overfiltration, and bleb dysesthesia. Regression analysis was applied to elucidate risk factors. RESULTS: The mean age of the patients was 66 years, 62.6% were male, and 88.5% were Chinese. The majority of the eyes had primary glaucoma (79.4%). The mean interval from the initial trabeculectomy or phaco-trabeculectomy to the bleb revision was 58.8 months. The overall success rate was 69.5%. By Kaplan-Meier survival analysis, the overall cumulative success range fell from 78.6% to 49.1% over 10 years. Eyes with early bleb leak had lower surgical success compared to eyes with late bleb leak, early overfiltration and late overfiltration (P = 0.026, log-rank test). The IOP improved significantly post-operatively for eyes with BRI, early bleb leak, late bleb leak, early overfiltration and overfiltration (P < 0.05). Vision improved significantly in eyes with early overfiltration, but deteriorated in eyes with BRI (P < 0.05). CONCLUSION: The overall success rate for surgical bleb revisions was good with complete resolution of the primary problem in the majority of cases. However, eyes with early bleb leak were less likely to have successful outcomes and should be monitored more closely post-operatively.

Evaluating CO2 laser-assisted sclerectomy surgery with mitomycin C combined with or without phacoemulsification in adult Asian glaucoma subjects.

PURPOSE: To evaluate and compare outcomes of CO2 laser-assisted sclerectomy surgery (CLASS) with mitomycin C (MMC) combined with or without phacoemulsification in adult Asian glaucoma patients. DESIGN: Retrospective, comparative study. METHODS: Adult Asian glaucoma patients who underwent CLASS alone or combined with phacoemulsification using standardized surgery by two trained glaucoma surgeons between 2014 and 2016 were identified. The main measures of outcome were: intraocular pressure (IOP), use of supplemental medical therapy, best-corrected visual acuity (BCVA), microperforations, macroperforations, and repeated intervention(s) for glaucoma. RESULTS: Forty-one eyes who underwent CLASS alone (13 eyes) or combined with phacoemulsification (28 eyes) were included. Overall, BCVA improved from 0.28 ± 0.19 to 0.14 ± 0.17, and 0.17 ± 0.19, 0.22 ± 0.24, and 0.18 ± 0.23 at 6, 12, 24, and 36 months, respectively. Mean IOP dropped from 17.9 ± 4.7 mmHg to 14.6 ± 5.5, 13.9 ± 3.3, 14.3 ± 3.6, and 14.1 ± 3.7 mmHg, and average number of medications reduced from 2.9 ± 0.9 to 0.2 ± 0.6, 0.5 ± 0.9, 1.0 ± 1.2, and 1.3 ± 1.4 at the same time points. There was no statistically significant difference in BCVA, IOP, and medication reduction between the two groups. CONCLUSIONS: CLASS combined with or without phacoemulsification was equally safe and effective, but yielded more modest results in our population.

Permeability of the porcine iris stroma.

Current literature has not considered or provided any data on the permeability of the iris stroma. In this study, we aimed to determine the hydraulic permeability of porcine irides from the isolated stroma. Fifteen enucleated porcine eyes were acquired from the local abattoir. The iris pigment epithelium was scraped off using a pair of forceps and the dilator muscles were pinched off using a pair of colibri toothed forceps. We designed an experimental setup, based on Darcy's law, and consisting of a custom 3D-printed pressure column using acrylonitrile butadiene styrene (ABS) plastic. PBS solution was passed through the iris stroma in a 180° arc shape, with a column height of approximately 204 mm (2000 Pa). Measurements of iris stromal thickness were conducted using optical coherence tomography (OCT). To measure flow rate, we measured the mass (volume) of PBS solution using a mass balance in approximately 1 min. Histology was performed using hematoxylin and eosin (H&E) and anti-smooth muscle antibody (anti-α-SMA) for validation. The permeability experiments demonstrated that the iris stroma is a biphasic tissue that allows fluid flow. Our image processing results determined the area of flow to be 7.55 mm2 and the tissue thickness to be between 180 and 430 µm. The hydraulic permeability of the porcine stroma, calculated using Darcy's law, was 5.13 ±â€¯2.39 × 10-5 mm2/Pa•s. Histological and immunochemical studies confirmed that the tissues used for this permeability study were solely iris stroma. Additionally, anti-α-SMA staining revealed staining specific for stromal blood vessels, with the notable absence of dilator and sphincter muscle staining. Our study combined experimental microscopic data with the theory of biphasic materials to investigate the hydraulic permeability of the iris stroma. This work will serve as a basis on which to validate future biomechanical studies of human irides with which may ultimately aid disease diagnosis and inform the design of novel treatments.

Aqueous shunts with mitomycin C versus aqueous shunts alone for glaucoma.

BACKGROUND: Glaucoma affects more than 70 million people worldwide, with about 10% being bilaterally blind, making it the leading cause of irreversible blindness globally. In patients with advanced glaucoma or those who have failed medical treatment without achieving adequate intraocular pressure (IOP) control, trabeculectomy (glaucoma filtration surgery where an ostium is created into the anterior chamber from underneath a partial thickness scleral flap to allow for aqueous flow out of the anterior chamber intointo the subconjunctival space forming a filtering bleb) and aqueous shunt surgery for more complex and refractory cases remain the mainstay therapies. Proliferation of fibrous tissue around an implanted aqueous shunt may block the diffusion of aqueous humour. Mitomycin C (MMC) is one of two commonly used adjunct antifibrotic agents used during aqueous shunt surgery to prevent proliferation of fibrous tissue. However, the effectiveness and safety of the use of intraoperative MMC during aqueous shunt surgery has not been established. OBJECTIVES: To evaluate the effectiveness and safety of MMC versus no MMC used during aqueous shunt surgery for reducing IOP in primary and secondary glaucoma. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 2); 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 13 February 2018. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in which one group of participants received MMC during aqueous shunt surgery and another group did not. We did not exclude studies based on outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed titles and abstracts from the literature searches. We obtained full-text reports of potentially relevant studies and assessed them for inclusion. Two review authors independently extracted data related to study characteristics, risk of bias, and outcomes. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included five RCTs, with a total of 333 eyes with glaucoma randomized, and identified two ongoing trials. All included trials examined the effect of MMC versus no MMC when used during aqueous shunt surgery for glaucoma. The trials included participants with different types of uncontrolled glaucoma. One study was conducted in China, one in Saudi Arabia, two in the USA, and one study was a multicenter study conducted in Brazil, Canada, Scotland, and USA. We assessed all trials as having overall unclear risk of bias due to incomplete reporting of study methods and outcomes; two of the five trials were reported only as conference abstracts.None of the included trials reported mean decrease from baseline in IOP; however, all five trials reported mean IOP at 12 months post-surgery. At 12 months, the effect of MMC on mean IOP compared with no MMC was unclear based on a meta-analysis of trials (mean difference -0.12 mmHg, 95% CI -2.16 to 2.41; low-certainty evidence). Two trial did not report sufficient information to include in meta-analysis, but reported that mean IOP was lower in the MMC group compared with the no MMC group at 12 months.None of the included trials reported mean change from baseline in visual acuity; however, one trial reported lower mean LogMAR values (better vision) in the MMC group than in the no MMC group at 12 months post-surgery. None of the included studies reported the proportion of participants with stable best-corrected visual acuity. Three trials reported that loss of vision was not significantly different between groups (no data available for meta-analysis).None of the included studies reported the proportion of participants with a postoperative hypertensive phase, which is defined as IOP > 21 mmHg within 3 months after surgery. Two trials reported adverse events (choroidal effusion, corneal edema, flat anterior chamber, and retinal detachment); however, due to small numbers of events and sample sizes, no clear difference between MMC and placebo groups was observed. AUTHORS' CONCLUSIONS: We found insufficient evidence in this review to suggest MMC provides any postoperative benefit for glaucoma patients who undergo aqueous shunt surgery. Data across all five included trials were sparse and the reporting of study methods required to assess bias was inadequate. Future RCTs of this intervention should report methods in sufficient detail to permit assessment of potential bias and estimate target sample sizes based on clinically meaningful effect sizes.

Pupillary Responses to Full-Field Chromatic Stimuli Are Reduced in Patients with Early-Stage Primary Open-Angle Glaucoma.

PURPOSE: To evaluate the ability of chromatic pupillometry to reveal abnormal pupillary responses to light in patients with early-stage primary open-angle glaucoma (POAG) and to test whether the degree of pupillometric impairment correlates with structural hallmarks of optic nerve damage in the disease. DESIGN: Cross-sectional study. PARTICIPANTS: Forty-six patients with early-stage POAG (63.4±8.3 years, 63% male, 87% ethnic-Chinese) and 90 age-matched healthy controls (61.4±8.6 years, 34% male, 89% ethnic-Chinese). Patients with POAG had a visual field mean deviation (VFMD) of -6 decibels or better on automated perimetry. METHODS: Each participant underwent a monocular 2-minute exposure to blue light (462 nm) followed by another 2-minute exposure to red light (638 nm) using a modified Ganzfeld dome equipped with a light-emitting diode lighting system. The light stimuli intensity was increased logarithmically to evaluate the combined extrinsic and intrinsic response of intrinsically photosensitive retinal ganglion cells (ipRGCs). Light-induced changes in horizontal pupil diameter were assessed monocularly using infrared pupillography. MAIN OUTCOME MEASURES: Baseline-adjusted, light-induced pupillary constriction amplitudes were calculated, and individual irradiance-response curves were constructed for each stimulus. Pupillary constriction amplitudes were compared between groups and across light intensities using a linear mixed model analysis. The linear relationship between pupillometric parameters and different structural and functional features of glaucoma was assessed using Pearson's correlation analysis. RESULTS: Light-induced pupillary constriction was reduced in patients with early-stage POAG compared with controls at moderate to high irradiances (≥11 Log photons/cm2/s) of blue (P = 0.003) and red (P < 0.001) light. Maximal pupillary constriction amplitude was correlated with retinal nerve fiber layer thickness (RNFL) thickness (blue: r = 0.51, P < 0.001; red: r = 0.45, P = 0.002) in patients with POAG but not in controls. Conversely, pupillometric parameters were not correlated with visual field scores in patients with early-stage POAG. CONCLUSIONS: Patients with early-stage POAG exhibit reduced pupillary responses to moderate and high irradiances of blue and red lights. This wavelength-independent functional alteration correlates with structural thinning of the RNFL and could be the consequence of dysfunction or loss of melanopsin expressing ipRGCs in the early stages of the disease.

A common variant near TGFBR3 is associated with primary open angle glaucoma.

Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10(-33)), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.

Visual Field Progression in Patients with Primary Angle-Closure Glaucoma Using Pointwise Linear Regression Analysis.

PURPOSE: To evaluate visual field (VF) progression and rate of glaucomatous VF loss in patients with primary angle-closure glaucoma (PACG) using pointwise linear regression (PLR) trend analysis. DESIGN: Clinic-based retrospective study. PARTICIPANTS: Primary angle-closure glaucoma patients with 5 or more reliable VF tests and with 5 years or more of follow-up. METHODS: Visual field progression was assessed by PROGRESSOR software version 3.7 (Medisoft, Leeds, United Kingdom) and was defined by the presence of at least 2 adjacent testing points located within the same hemifield that showed progression with a change of -1 dB/year or more (P < 0.01) for inner points or -2 dB/year or more (P < 0.01) for edge points. We also performed a logistic regression analysis to determine the variables associated with rapid progression (defined as mean slope of progressing points ≥-1.5 dB/year). MAIN OUTCOME MEASURES: Visual field progression and rate of VF loss. RESULTS: Of the 1296 patients who were assessed, 398 (30.7%) fulfilled the inclusion criteria of 5 or more VFs and 5 years or more of follow-up. Visual field progression was observed in 63 of 398 eyes (15.8%) according to the PLR criteria. The overall mean rate of VF change for these patients was -0.12±0.51 dB/year over a mean follow-up period of 10.4±3.7 years. There were no significant differences in the age, gender distribution, follow-up duration, or number of VFs between those who showed progression and those who did not (all P > 0.05). The most common sector of VF progression was the superior arcuate area (65%). Rapid progression was found in 36 patients (57%). Multiple logistic regression analysis revealed older age and higher vertical cup-to-disc ratio (VCDR) at presentation as predictors of rapid progression (all P < 0.005) in the progressing group (n = 63). CONCLUSIONS: In patients with PACG being managed in a hospital setting, VF progression was noted in 15.8%, and the overall rate of VF loss was -0.12±0.51 dB/year. The superior arcuate was the most common sector of progression. Older age and higher VCDR at presentation were associated with rapid progression.

ABCC5, a gene that influences the anterior chamber depth, is associated with primary angle closure glaucoma.

Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size =  -0.045 mm, P = 8.17 × 10(-9)). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45 × 10(-9); 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.

Pattern of Visual Field Loss in Primary Angle-Closure Glaucoma Across Different Severity Levels.

PURPOSE: To investigate the patterns of visual field (VF) defects in primary angle-closure glaucoma (PACG) across different severity levels and to assess hemifield differences within each severity level. DESIGN: Cross-sectional study. PARTICIPANTS: Three hundred four patients diagnosed with PACG were recruited from glaucoma clinics at a Singapore hospital. METHODS: Point-wise total deviation values were recorded from the static automated perimetry (Swedish interactive threshold algorithm standard program 24-2; Humphrey model 750 [Carl Zeiss Meditec, Dublin, CA]) printouts. Patients were excluded if they had unreliable VFs (fixation losses >33% and false-positive responses >15%), had undergone only 10-2 VF testing, had VF defects not typical of glaucoma, or had undergone cataract extraction. Mild, moderate, and severe VF loss were defined by a mean deviation of -6.00 dB or more, -6.01 to -12.00 dB, and -12.01 dB or less, respectively. Each hemifield was divided into regions according to glaucoma hemifield test sectors. The average mean deviation (MD) of each region was obtained using total deviation values. MAIN OUTCOME MEASURES: Between- and within-hemifield differences of the regions across the severity levels. RESULTS: After excluding ineligible cases, 249 patients with PACG were included in the analysis. Mean age of the patients was 65.7±8.6 years, with a 1:1 gender ratio. The number of patients who had mild, moderate, and severe VFs was 72 (28.9%), 78 (31.3%), and 99 (39.8%), respectively. For between-hemifield comparisons, all regions in the superior hemifield had worse MDs compared with their counterparts in the inferior hemifield across the severity spectrum. Likewise, for within-hemifield comparisons, MDs of the regions gradually worsened with increasing distance from the fixation point. CONCLUSIONS: In this group of clinic-based PACG patients, the superior hemifield was found to be affected more severely than the inferior hemifield, and the differences between them increased with worsening disease severity. The damage was consistently more pronounced in the nasal area.

Argon Laser Peripheral Iridoplasty for Primary Angle-Closure Glaucoma: A Randomized Controlled Trial.

PURPOSE: To determine the effectiveness of argon laser peripheral iridoplasty (ALPI) in primary angle closure (PAC) and primary angle-closure glaucoma (PACG). DESIGN: Randomized controlled trial. PARTICIPANTS: Eighty PAC or PACG subjects who underwent laser iridotomy (LI) and had at least 180° of persistent appositional angle closure and intraocular pressure (IOP) of more than 21 mmHg were enrolled. METHODS: Subjects were randomized to receive either 360° ALPI (Visulas 532s; Carl Zeiss Meditec, Jena, Germany) or medical therapy (Travoprost 0.004%; Alcon-Couvreur, Puurs, Antwerp, Belgium). Repeat ALPI was performed if the IOP reduction was less than 20% from baseline along with inadequate angle widening at the month 1 or month 3 visit. Intraocular pressure was controlled with systematic addition of medications when required. MAIN OUTCOME MEASURES: The primary outcome measure was success rates after ALPI at 1 year. Complete success was defined as an IOP of 21 mmHg or less without medication, and qualified success was defined as an IOP of 21 mmHg or less with medication. Failure was defined as an IOP more than 21 mmHg despite additional medications or requiring glaucoma surgery. RESULTS: Forty subjects (51 eyes) were randomized to ALPI and 40 subjects (55 eyes) were randomized to medical therapy. Complete success (IOP ≤21 mmHg without medication) was achieved in 35.0% eyes of the ALPI group compared with 85.0% of eyes in the prostaglandin analog (PGA) group (P < 0.001), and qualified success (IOP ≤21 mmHg with medication) was achieved in 35.0% and 7.5%, respectively (P = 0.003). The IOP decreased by 4.9 mmHg (95% confidence interval [CI], 3.5-6.3 mmHg) in the ALPI group (P < 0.001) and by 6.1 mmHg (95% CI, 5.1-7.1 mmHg) in the medication group (P < 0.001). A failure rate of 30.0% was noted in the ALPI group compared with 7.5% in the medication group (P = 0.01). No treatment-related complications were recorded in either group. CONCLUSIONS: After 1 year, ALPI was associated with higher failure rates and lower IOP reduction compared with PGA therapy in eyes with persistent appositional angle closure and raised IOP after LI.

Factors influencing the pupillary light reflex in healthy individuals.

PURPOSE: To determine the ocular anatomical factors influencing the pupillary light reactions to different wavelengths of light, measured with chromatic pupillometry. METHODS: Community-based, cross-sectional study including subjects with normal ocular health (ages 50-79 years). Direct pupillary responses to continuously increasing irradiances (6.8 to 13.8 log photons cm(-2) s(-1)) of red (631 nm) and blue (469 nm) light were measured, using a dedicated infrared pupillometer. All subjects underwent swept source optical coherence tomography (SS-OCT, CASIA SS-1000, Tomey Corporation, Nagoya, Japan) and noncontact partial coherence laser interferometry (Lenstar LS900, Haag-Streit AG, Switzerland). Univariate and multivariable regression analyses were performed to determine the anatomical features influencing pupillographic parameters. RESULTS: Among the 177 included subjects, 167 (94.4 %) were Chinese and 116 (65.5 %) female. The average baseline pupil diameter in darkness (ß = -0.080, p < 0.001) and the amplitude of the relative pupillary constriction (ß = -0.233, p = 0.006) to blue light decreased with age. The amplitude of pupillary constriction was significantly larger in patients with a thinner iris, in response to stimulation with blue (ß = -0.321, p < 0.001) and red light (ß = -0.336, p < 0.001). Other ocular parameters (i.e., lens vault, anterior chamber depth width, iris volume, iris curvature, and lens thickness) were not significantly associated with pupillometric outcomes. CONCLUSIONS: The amplitude of the pupillary light constriction to chromatic photic stimuli is reduced with increasing age and iris thickness in subjects with normal ocular health, a finding which needs to be integrated into future pupillometric studies.

Determinants of pupil diameters and pupil dynamics in an adult Chinese population.

BACKGROUND: To investigate the determinants of pupil diameter (PD), amplitude of pupil diameter change (PD-change) and speed of pupil constriction (SPC) using video anterior segment optical coherence tomography (AS-OCT) in a population-based sample of Chinese adults. METHODS: Chinese adults aged 40 to 80 years who were free from glaucoma were consecutively recruited from the population-based Singapore Chinese Eye Study. The SPC was measured by AS-OCT videography. Univariate and multivariate analyses were performed to examine the effects of demographic and ocular biometric factors (e.g., axial length [AL], anterior chamber depth [ACD], baseline PD, iris thickness at the area of the dilator muscle [ITDMR], iris area [IA], and iris bowing [IB]) on SPC, PD, and PD-change. RESULTS: A total of 266/302 (89.5 %) AS-OCT videos of eligible eyes were available for analysis. Among these subjects, 64.3 % were women, and the mean age (± standard deviation [SD]) was 56 ± 8.3 years. SPC was not associated with sex. In multiple regression analyses, SPC was independently associated with baseline PD (ß = 0.116, p = 0.006). Baseline PD was independently associated with ACD (ß = 0.341, p < 0.001), TISA 500 (ß = -4.513, p < 0.001), IA (ß = -2.796, p < 0.001), and ITDMR (ß = 6.573, p < 0.001). PD-change was independently associated with ACD (ß = 0.256, p < 0.001), IA (ß = -1.507, p < 0.001), IB (ß = 0.630, p = 0.011), and ITDMR (ß = 3.124, p < 0.001). CONCLUSIONS: Among normal eyes in an adult Chinese population, SPC was associated with larger baseline PD. Larger baseline PD and greater PD change form dark to light were associated with greater ACD, with smaller IA and thicker ITDMR.

Distinct iris gene expression profiles of primary angle closure glaucoma and primary open angle glaucoma and their interaction with ocular biometric parameters.

BACKGROUND: This study aimed to evaluate differences in iris gene expression profiles between primary angle closure glaucoma (PACG) and primary open angle glaucoma (POAG) and their interaction with biometric characteristics. DESIGN: Prospective study. PARTICIPANTS: Thirty-five subjects with PACG and thirty-three subjects with POAG who required trabeculectomy were enrolled at the Singapore National Eye Centre, Singapore. METHODS: Iris specimens, obtained by iridectomy, were analysed by real-time polymerase chain reaction for expression of type I collagen, vascular endothelial growth factor (VEGF)-A, -B and -C, as well as VEGF receptors (VEGFRs) 1 and 2. Anterior segment optical coherence tomography (ASOCT) imaging for biometric parameters, including anterior chamber depth (ACD), anterior chamber volume (ACV) and lens vault (LV), was also performed pre-operatively. MAIN OUTCOME MEASURES: Relative mRNA levels between PACG and POAG irises, biometric measurements, discriminant analyses using genes and biometric parameters. RESULTS: COL1A1, VEGFB, VEGFC and VEGFR2 mRNA expression was higher in PACG compared to POAG irises. LV, ACD and ACV were significantly different between the two subgroups. Discriminant analyses based on gene expression, biometric parameters or a combination of both gene expression and biometrics (LV and ACV), correctly classified 94.1%, 85.3% and 94.1% of the original PACG and POAG cases, respectively. The discriminant function combining genes and biometrics demonstrated the highest accuracy in cross-validated classification of the two glaucoma subtypes. CONCLUSIONS: Distinct iris gene expression supports the pathophysiological differences that exist between PACG and POAG. Biometric parameters can combine with iris gene expression to more accurately define PACG from POAG.

Pupillary Responses to High-Irradiance Blue Light Correlate with Glaucoma Severity.

PURPOSE: To evaluate whether a chromatic pupillometry test can be used to detect impaired function of intrinsically photosensitive retinal ganglion cells (ipRGCs) in patients with primary open-angle glaucoma (POAG) and to determine if pupillary responses correlate with optic nerve damage and visual loss. DESIGN: Cross-sectional study. PARTICIPANTS: One hundred sixty-one healthy controls recruited from a community polyclinic (55 men; 151 ethnic Chinese) and 40 POAG patients recruited from a glaucoma clinic (22 men; 35 ethnic Chinese) 50 years of age or older. METHODS: Subjects underwent monocular exposure to narrowband blue light (469 nm) or red light (631 nm) using a modified Ganzfeld dome. Each light stimulus was increased gradually over 2 minutes to activate sequentially the rods, cones, and ipRGCs that mediate the pupillary light reflex. Pupil diameter was recorded using an infrared pupillography system. MAIN OUTCOME MEASURES: Pupillary responses to blue light and red light were compared between control subjects and those with POAG by constructing dose-response curves across a wide range of corneal irradiances (7-14 log photons/cm(2) per second). In patients with POAG, pupillary responses were evaluated relative to standard automated perimetry testing (Humphrey Visual Field [HVF]; Carl Zeiss Meditec, Dublin, CA) and scanning laser ophthalmoscopy parameters (Heidelberg Retinal Tomography [HRT]; Heidelberg Engineering, Heidelberg, Germany). RESULTS: The pupillary light reflex was reduced in patients with POAG only at higher irradiance levels, corresponding to the range of activation of ipRGCs. Pupillary responses to high-irradiance blue light associated more strongly with disease severity compared with responses to red light, with a significant linear correlation observed between pupil diameter and HVF mean deviation (r = -0.44; P = 0.005) as well as HRT linear cup-to-disc ratio (r = 0.61; P < 0.001) and several other optic nerve head parameters. CONCLUSIONS: In glaucomatous eyes, reduced pupillary responses to high-irradiance blue light were associated with greater visual field loss and optic disc cupping. In POAG, a short chromatic pupillometry test that evaluates the function of ipRGCs can be used to estimate the degree of damage to retinal ganglion cells that mediate image-forming vision. This approach could prove useful in detecting glaucoma.

A Genetic Variant in TGFBR3-CDC7 Is Associated with Visual Field Progression in Primary Open-Angle Glaucoma Patients from Singapore.

PURPOSE: To investigate whether known genetic loci for primary open-angle glaucoma (POAG) are associated with visual field (VF) progression in patients from a Singaporean Chinese population. DESIGN: Retrospective study. PARTICIPANTS: Patients with 5 or more reliable VF measurements who were being followed up at a Singapore hospital. METHODS: Visual field progression was identified using Progressor software version 3.7 (Medisoft, Leeds, United Kingdom) and defined by pointwise linear regression (PLR) criteria as follows: any 2 contiguous points in the same hemifield progressing (≤-1.00 dB/year for inner points and ≤-2.00 dB/year for edge points; P < 0.01). Single nucleotide polymorphisms (SNPs) and their proxies from 10 POAG-associated loci (CAV1-CAV2, CDKN2B-AS1, SIX1-SIX6, an intergenic region on chromosome 8q22, ABCA1, GAS7, AFAP1, GMDS, PMM2, and TGFBR3-CDC7) identified from genome-wide association studies were tested for association with VF progression using logistic regression with an additive genetic model adjusting for age, gender, average intraocular pressure (IOP), central corneal thickness (CCT), and baseline vertical cup-to-disc ratio (VCDR). MAIN OUTCOME MEASURE: Visual field progression. RESULTS: Of the 1334 patients included in the study, 469 subjects (35.1%) completed 5 or more reliable VF measurements (mean follow-up, 9.01 years; standard deviation, 5.00 years). The mean age of patients was 59.6 years (standard deviation, 9.0 years); 305 patients were men and all were Chinese. The average IOP in eyes fulfilling PLR progression was 16.5 mmHg versus 17.7 mmHg in those who did not (P = 0.52). Univariate analysis revealed that increased VCDR (P = 0.003), reduced CCT (P = 0.045), and reduced superior and inferior retinal nerve fiber layer thickness (P = 0.01, respectively) were associated with VF progression. No clinical or structural features were associated significantly with VF progression on multivariate analysis. The rs1192415 index SNP in TGFBR3-CDC7 (P = 0.002; odds ratio, 6.71 per risk allele) was the only SNP associated with VF progression. CONCLUSIONS: The presence of the index SNP rs1192415 (TGFBR3-CDC7) was associated with VF progression in POAG patients. These findings warrant further investigation in independent cohorts.

The role of lens extraction in the current management of primary angle-closure glaucoma.

PURPOSE OF REVIEW: Lens extraction for primary angle-closure glaucoma (PACG) is a subject of increased interest recently, with advocates promoting its benefits of anatomical opening of the angle, intraocular pressure (IOP) reduction and improved vision. The present review seeks to evaluate recent available evidence to provide clarity on this potential intervention within the armamentarium of approaches for PACG. RECENT FINDINGS: The emergence of recent case-control studies, cohort studies and randomized controlled trials has provided a stronger evidence base to equip ophthalmic surgeons with the necessary information to utilize lens extraction in the management of PACG, and to consider whether this should be combined with trabeculectomy or goniosynechialysis. Imaging modalities such as anterior segment optical coherence tomography have yielded new insights into the mechanical features of the lens in angle closure, with the lens thickness and lens vault now quantifiable. A trend is emerging regarding the improvement in IOP control, reduced complication rates and reduced need for IOP-lowering medications in patients who undergo lens extraction for PACG. These issues are discussed, along with aspects of preoperative assessment and surgical techniques. SUMMARY: Good outcomes in terms of long-term IOP control have been found following lens extraction for PACG. Lens extraction should be considered in patients with PACG, especially with hyperopia, or a thick and anteriorly vaulted lens.

Angle-closure glaucoma in Asians: comparison of biometric and anterior segment parameters between Japanese and Chinese subjects.

PURPOSE: To compare anterior segment parameters in Chinese and Japanese subjects with angle closure using anterior segment optical coherence tomography (ASOCT). METHODS: One hundred and forty-two Japanese and one hundred and ninety-two Chinese subjects with primary angle closure (PAC) or primary angle-closure glaucoma (PACG) were recruited. All participants underwent A-scan biometry and ASOCT imaging (Visante, Carl Zeiss Meditec, Dublin, CA, USA). Customized software was used to measure ASOCT parameters in horizontal ASOCT scans. The parameters were compared, and multivariate analysis was performed to determine predictors of angle opening distance at 750 µm from the scleral spur (AOD750). RESULTS: Ethnic difference evaluated by multiple linear regression adjusted for age, gender, spherical equivalent, pupil diameter, and axial length showed that Japanese angle-closure subjects had significantly shallower anterior chamber depth (ACD;ß = -0.3, p < 0.001), smaller anterior chamber area (ACA; ß = -0.21, p = 0.02) and volume (ACV; ß = -0.19, p = 0.01), greater lens vault (LV, ß = 0.3, p < 0.001), lens thickness (LT; ß = 0.48, p < 0.001), greater iris area (IArea; ß = 0.19, p = 0.01), and more curved iris (ICurv; ß = 0.16, p = 0.04). The significant determinants of AOD750 were iris thickness (IT; ß = -0.21, p = 0.04), ICurv (ß = -0.17, p = 0.04), pupil diameter (PD; ß = -0.34, p = 0.001) and ACV (ß = 0.32, p < 0.001) in Japanese; and IT (ß = -0.25, p = 0.001), ACV (ß = 0.37, p < 0.001), PD (ß = -0.26, p = 0.001), and LV (ß = -0.18, p = 0.03) in Chinese. CONCLUSIONS: Compared to Chinese, Japanese angle-closure eyes have smaller and more crowded anterior segment with thicker lenses. ACV, IT, and PD are important factors for angle width in both races. These results suggest possible ethnic differences in angle-closure mechanism(s).