Aqueous humour protein dysregulation in Asian eyes with primary open angle glaucoma.

The pathophysiology of Primary Open Angle Glaucoma (POAG) remains poorly understood. Through proteomic analysis of aqueous humour (AH) from POAG patients, we aim to identify changes in protein composition of these samples compared to control samples. High resolution mass spectrometry-based TMT6plex quantitative proteomics analysis is performed on AH samples collected from POAG patients, and compared against a control group of patients with cataracts. Data are available via ProteomeXchange with identifier PXD033153. 1589 proteins were quantified from the aqueous samples using Proteome Discoverer version 2.2 software. Among these proteins, 210 were identified as unique master proteins. The proteins which were up or down-regulated by ±3 fold-change were considered significant. Human neuroblastoma full-length cDNA clone CS0DD006YL02 was significantly upregulated in patients with severe POAG on >2 medications, while actin, cytoplasmic 1, V2-7 protein (fragment), immunoglobulin-like polypeptide 1 and phosphatidylethanolamine-binding protein 4 were only present in these patients with severe POAG on >2 medications. Beta-crystallin B1 and B2, Gamma-crystallin C, D and S were significantly downregulated in the severe POAG ≤2 glaucoma medications group. Beta-crystallin B2, Gamma-crystallin D and GCT-A9 light chain variable region (fragment) were significantly downregulated in the non-severe POAG group. Actin, cytoplasmic 1 was significantly upregulated in subjects with severe POAG who required more than 2 glaucoma medications. Crystallins (Beta-crystallin B1 and B2, Gamma-crystallin C, D and S) were significantly downregulated in subjects with severe POAG who required less than 2 glaucoma medications.

Comparison of Efficacy of Combined Phacoemulsification and iStent Inject versus Combined Phacoemulsification and Hydrus Microstent.

Aim: This study aims to compare the efficacy and safety of combined phacoemulsification with iStent inject (Phaco-iStent) and Hydrus microstent (Phaco-Hydrus). Methods: This was a retrospective comparative study of patients who underwent Phaco-iStent from April 2019 to August 2020 and Phaco-Hydrus from August 2019 to December 2020 at a tertiary eye centre in Singapore. Sixty-nine Phaco-iStent eyes and 49 Phaco-Hydrus eyes were included in this study. Complete surgical success was defined as freedom from second glaucoma surgery, Intraocular pressure (IOP) of 18 mmHg or less, and discontinuation of all antiglaucoma medications. Results: At 12 months, both Phaco-iStent and Phaco-Hydrus groups had comparable surgical success rate (68.1% vs 51%, p=0.061), reduction in antiglaucoma medication use (-1.3 ± 0.1 vs -1.4 ± 0.10, p=0.880) and intraocular pressure reduction (-1.1 ± 0.5 mmHg vs -1.6 ± 0.9 mmHg, p=0.323). Overall intraoperative and postoperative complications rate were similar in both groups, though hyphema was more commonly seen in early postoperative period in the Phaco-Hydrus compared to the Phaco-iStent group (8% vs 0%, p=0.028), with majority of cases resolving without any need for surgical intervention. Device obstruction was also more common in the Phaco-Hydrus group compared to the Phaco-iStent group (14% vs 4.3%, p=0.04). Conclusion: Phaco-iStent and Phaco-Hydrus have similar surgical efficacy and safety profiles at 12 months.

Prospective 12-month outcomes of combined iStent inject implantation and phacoemulsification in Asian eyes with normal tension glaucoma.

BACKGROUND: Glaucoma is the leading cause of irreversible blindness. Normal tension glaucoma (NTG) is a subset of open-angle glaucoma, demonstrating glaucomatous optic nerve damage in the absence of raised intraocular pressure (IOP). NTG is more prevalent in Asian populations. While generally slow-progressing, NTG may be associated with significant central visual field loss. In recent years, minimally invasive glaucoma surgery has been added to the armamentarium of glaucoma surgery. This prospective study aims to evaluate 12-month surgical outcomes of combined iStent inject (Glaukos Corporation, Laguna Hills, CA) implantation and phacoemulsification in Asian eyes with NTG. METHODS: This is a prospective, single-centre case series of 30 eyes followed up until 12 months after surgery. Outcome measures included IOP, number of glaucoma medications, best-corrected visual acuity (BCVA) and intra and postoperative complications. RESULTS: Mean age of subjects was 73.1 ± 6.3 years. Majority were ethnic Chinese (n = 27, 90%). Baseline medicated mean IOP was 13.8 ± 2.4 mmHg and mean number of glaucoma medications was 1.3 ± 0.7. Mean Humphrey visual field mean deviation was - 13.7 ± 7.6. The mean IOP reduction at all timepoints from postoperative month (POM) 3 onwards was statistically significant (all P < 0.05), with mean reduction of 1.2 mmHg (95% CI: 0.1-2.2, P = 0.037) by POM12. There was statistically significant reduction in mean number of medications from postoperative day (POD) 1 onwards (all P < 0.05), with mean decrease of 1.0 medication (95% CI: 0.9-1.1, P < 0.001) by POM12. By POM12, 25 (83.3%) eyes were medication-free. Three (10%) eyes had stent occlusion by iris requiring laser iridoplasty. One eye had gross hyphema which resolved on conservative management before POM1. Mean BCVA improved from the baseline 0.3 ± 0.3 logMAR to 0.1 ± 0.1 logMAR postoperatively (P < 0.001). There were no major adverse or sight-threatening events. No eyes required further glaucoma surgery during the 12-month follow-up period. CONCLUSION: Asian eyes with NTG which underwent combined iStent inject implantation and phacoemulsification demonstrated a significant and sustained reduction in IOP and glaucoma medications, up to 12 months postoperatively.

Standalone XEN45 Gel Stent implantation in the treatment of open-angle glaucoma: A systematic review and meta-analysis.

The XEN45 Gel Stent (Allergan Inc., Irvine, CA) allows the drainage of aqueous into the sub-conjunctival space, through a minimally-invasive approach. This systematic review and meta-analysis evaluates its intraocular pressure (IOP)-lowering efficacy and complications in the treatment of open-angle glaucoma. Fourteen studies comprising 963 eyes were included. IOP decreased significantly (P < 0.001) across all timepoints (1 day, 1 week, 1, 3, 6, 12, 18, and 24 months) with a mean decrease of 7.44 mm Hg (95%CI:4.91-9.97) at 24 months. IOP-lowering medications decreased significantly (P < 0.001) across all timepoints (1 week, 1, 3, 6, 12, 18, 24 months) with a mean reduction of 1.67 medications (95%CI:1.28-2.06) at 24 months. Numerical hypotony occurred in 39% (95%CI:14%-67%) and stent exposure in 1% (95%CI:0%-2%) of eyes. 38% (95%CI:30%-46%) of eyes required at least one postoperative needling, with an average of 0.6 (95%CI:0.37-0.81) needlings per eye. Standalone XEN45 Gel Stent implantation is effective in lowering IOP in open-angle glaucoma. Transient numerical hypotony is the most common postoperative complication. Sight-threatening complications are rare. Postoperative needling may be required to maintain IOP-lowering outcomes; however, the overall quality of current evidence is low, with the need for more randomized controlled trials and outcomes measured with a clinically meaningful definition of success.

Glaucoma screening using an attention-guided stereo ensemble network.

Glaucoma is a chronic eye disease, which causes gradual vision loss and eventually blindness. Accurate glaucoma screening at early stage is critical to mitigate its aggravation. Extracting high-quality features are critical in training of classification models. In this paper, we propose a deep ensemble network with attention mechanism that detects glaucoma using optic nerve head stereo images. The network consists of two main sub-components, a deep Convolutional Neural Network that obtains global information and an Attention-Guided Network that localizes optic disc while maintaining beneficial information from other image regions. Both images in a stereo pair are fed into these sub-components, the outputs are fused together to generate the final prediction result. Abundant image features from different views and regions are being extracted, providing compensation when one of the stereo images is of poor quality. The attention-based localization method is trained in a weakly-supervised manner and only image-level annotation is required, which avoids expensive segmentation labelling. Results from real patient images show that our approach increases recall (sensitivity) from the state-of-the-art 88.89% to 95.48%, while maintaining precision and performance stability. The marked reduction in false-negative rate can significantly enhance the chance of successful early diagnosis of glaucoma.

Comparison of Surgical Outcomes of Sponge Application versus Subconjunctival Injection of Mitomycin-C during Combined Phacoemulsification and Trabeculectomy Surgery in Asian Eyes.

PURPOSE: To compare the outcomes of combined phacoemulsification-trabeculectomy surgery with intraoperative sponge-applied versus subconjunctival injection of mitomycin-C (MMC) in Asian eyes. METHODS: This was a retrospective review of 95 eyes that consecutively underwent combined phacoemulsification-trabeculectomy surgery in a tertiary eye center in Singapore from January 2013 to June 2014. Data collected included intraocular pressure (IOP), best corrected visual acuity, and number of glaucoma medications. Outcome measures included postoperative IOP and complications at various timepoints up to 12 months after surgery. RESULTS: Twenty eyes (21.1%) received 0.2 mg/ml subconjunctival MMC injection ("Group 1") and 75 (78.9%) received 0.4 mg/ml sponge-applied MMC ("Group 2"). There was no difference between groups in demographics, IOP, and number of glaucoma medications preoperatively. There was a reduction in IOP at postoperative month (POM) 1, 6, and 12 in both the groups (POM12: Group 1, -2.8 ± 5.36 mmHg, P < 0.001; Group 2, -5.8 ± 6.29 mmHg, P = 0.054). At POM1, Group 2 showed a trend toward greater IOP reduction (-5.89 ± 7.67 mmHg vs. -1.55 ± 5.68 mmHg, P = 0.061). However, at both POM6 and POM12, there was no statistically significant difference in IOP reduction between the two groups. At POM12, complete success, defined as achieving an IOP of between 6 and 15 mmHg without the use of antiglaucoma medications, was achieved in 11 (55%) eyes in Group 1 and 48 (64%) in Group 2 (P = 0.9). There was a lower rate of postoperative hypotony in the Group 1 (0%) compared to Group 2 (8%) (P = 0.34). CONCLUSION: Combined phacoemulsification-trabeculectomy with subconjunctival MMC injection has comparable outcomes to that with sponge-applied MMC, with a similar reduction in IOP at 1, 6, and 12 months postoperatively and a lower postoperative complication rate.

Standalone XEN45 Gel Stent implantation versus combined XEN45-phacoemulsification in the treatment of open angle glaucoma-a systematic review and meta-analysis.

PURPOSE: The XEN45 Gel Stent is currently the only FDA-approved sub-conjunctival minimally invasive glaucoma surgery (MIGS) procedure. It has been used worldwide either as a standalone implantation procedure or in combination with phacoemulsification surgery. Concomitant phacoemulsification is understood to influence outcomes of traditional subconjunctival filtering surgery. However, the comparative efficacy between standalone XEN45 Gel Sent implantation ("Standalone XEN45") and combined XEN-phacoemulsification surgery ("XEN45-Phaco") remains unclear. This study aims to appraise current literature to compare the efficacy of Standalone XEN45 and XEN45-Phaco in open-angle glaucoma. METHODS: A comprehensive search of PubMed, CINAHL, CENTRAL databases was performed with the terms "Xen surgery" followed by selective vetting. Pilot, cohort, observational studies and randomised controlled trials that included at least 10 patients undergoing either Standalone XEN45 or XEN45-Phaco surgeries for the treatment of open-angle glaucoma were deemed eligible for inclusion after independent assessment by 2 authors. The search workflow was reported according to the PRISMA guidelines. Data was pooled using random-effects model. A meta-analysis of continuous outcome and proportions was performed using the meta routine in R v3.2.1. RESULTS: Ten studies were included. There was a statistically significant difference in IOP reduction favouring Standalone XEN45 at post-operative day 1, week 1, months 1, 3 and 6. There was a statistically significant difference in decrease in IOP-lowering medications favouring Standalone XEN45 at post-operative week 1 and month 1. CONCLUSION: Standalone XEN45 has superior IOP-lowering outcomes compared to XEN45-Phaco in the early post-operative period, up to 6 months after surgery.

Optical coherence tomography angiography of the macula and optic nerve head: microvascular density and test-retest repeatability in normal subjects.

BACKGROUND: Despite the potential usefulness of optical coherence tomography angiography in retinal and optic disc conditions, the reliability of the imaging modality remains unclear. This study set out to measure the microvascular density of macula and optic disc by mean of optical coherence tomography angiography and report the repeatability of the vessel density measurements. METHODS: Cross sectional observational cohort study. Subjects with normal eyes were recruited. Two sets of optical coherence tomography angiography images of macula and optic nerve head were acquired during one visit. Novel in-house developed software was used to count the pixels in each images and to compute the microvessel density of the macula and optic disc. Data were analysed to determine the measurement repeatability. RESULTS: A total of 176 eyes from 88 consecutive normal subjects were recruited. For macular images, the mean vessel density at superficial retina, deep retina, outer retina and choriocapillaries segment was OD 0.113 and OS 0.111, OD 0.239 and OS 0.230, OD 0.179 and OS 0.164, OD 0.237 and OS 0.215 respectively. For optic disc images, mean vessel density at vitreoretinal interface, radial peripapillary capillary, superficial nerve head and disc segment at the level of choroid were OD 0.084 and OS 0.085, OD 0.140 and OS 0.138, OD 0.216 and OS 0.209, OD 0.227 and OS 0.236 respectively. The measurement repeatability tests showed that the coefficient of variation of macular scans, for right and left eyes, ranged from 6.4 to 31.1% and 5.3 to 59.4%. Likewise, the coefficient of variation of optic disc scans, for right and left eyes, ranged from 14.3 to 77.4% and 13.5 to 75.3%. CONCLUSIONS: Optical coherence tomography angiography is a useful modality to visualise the microvasculature plexus of macula and optic nerve head. The vessel density measurement of macular scan by mean of optical coherence tomography angiography demonstrated good repeatability. The optic disc scan, on the other hand, showed a higher coefficient of variation indicating a lower measurement repeatability than macular scan. Interpretation of optical coherence tomography angiography should take into account test-retest repeatability of the imaging system. TRIAL REGISTRATION: National Healthcare Group Domain Specific Review Board ( NHG DSRB ) Singapore. DSRB Reference: 2015/00301.

Effect of head tilt on repeatability of optic nerve head parameters using cirrus spectral-domain optical coherence tomography.

AIM: To assess the repeatability of measuring optic nerve head (ONH) parameters using the Cirrus optical coherence tomography (OCT), as well as to assess the effect of head tilt on these measurements. METHODS: Thirty healthy participants with no evidence of glaucoma were recruited for the study. Visual acuity, intraocular pressure, standard automated perimetry and ocular examination were performed for each participant. One eye was then randomly selected and scanned undilated with the Cirrus OCT in 3 positions (neutral, 30° right tilt and 30° left tilt). RESULTS: Data collected from 29 eyes were used for analysis. One patient was omitted due to poor scan quality. The repeatability of the ONH parameters was analyzed using analysis of variance, coefficient of variation (COV) and intraclass correlation coefficient (ICC). Analysis of variance showed no statistically significant difference between 3 scans in a single position. There was good agreement between measurements (ICC 0.919-0.996, COV 1.94%-5.48%). Even with the presence of head tilt, repeated scans in the 3 positions showed good agreement as well (ICC 0.888-0.996, COV 2.04%-5.39%). CONCLUSION: Serial measurements of ONH parameters using the Cirrus OCT are found to have good repeatability. The ONH parameters with Cirrus OCT also maintain good repeatability despite head tilt.

Agreement of angle closure assessments between gonioscopy, anterior segment optical coherence tomography and spectral domain optical coherence tomography.

AIM: To determine angle closure agreements between gonioscopy and anterior segment optical coherence tomography (AS-OCT), as well as gonioscopy and spectral domain OCT (SD-OCT). A secondary objective was to quantify inter-observer agreements of AS-OCT and SD-OCT assessments. METHODS: Seventeen consecutive subjects (33 eyes) were recruited from the study hospital's Glaucoma clinic. Gonioscopy was performed by a glaucomatologist masked to OCT results. OCT images were read independently by 2 other glaucomatologists masked to gonioscopy findings as well as each other's analyses of OCT images. RESULTS: Totally 84.8% and 45.5% of scleral spurs were visualized in AS-OCT and SD-OCT images respectively (P<0.01). The agreement for angle closure between AS-OCT and gonioscopy was fair at k=0.31 (95% confidence interval, CI: 0.03-0.59) and k=0.35 (95% CI: 0.07-0.63) for reader 1 and 2 respectively. The agreement for angle closure between SD-OCT and gonioscopy was fair at k=0.21 (95% CI: 0.07-0.49) and slight at k=0.17 (95% CI: 0.08-0.42) for reader 1 and 2 respectively. The inter-reader agreement for angle closure in AS-OCT images was moderate at 0.51 (95% CI: 0.13-0.88). The inter-reader agreement for angle closure in SD-OCT images was slight at 0.18 (95% CI: 0.08-0.45). CONCLUSION: Significant proportion of scleral spurs were not visualised with SD-OCT imaging resulting in weaker inter-reader agreements. Identifying other angle landmarks in SD-OCT images will allow more consistent angle closure assessments. Gonioscopy and OCT imaging do not always agree in angle closure assessments but have their own advantages, and should be used together and not exclusively.