Metabolomic profiling of aqueous humor from glaucoma patients - The metabolomics in surgical ophthalmological patients (MISO) study.

Glaucoma is still a poorly understood disease with a clear need for new biomarkers to help in diagnosis and potentially offer new therapeutic targets. We aimed to determine if the metabolic profile of aqueous humor (AH) as determined by nuclear magnetic resonance (NMR) spectroscopy allows the distinction between primary open-angle glaucoma patients and control subjects, and to distinguish between high-tension (POAG) and normal-tension glaucoma (NTG). We analysed the AH of patients with POAG, NTG and control subjects (n = 30/group). 1H NMR spectra were acquired using a 400 MHz spectrometer. Principle component analysis (PCA), machine learning algorithms and descriptive statistics were applied to analyse the metabolic variance between groups, identify the spectral regions, and hereby potential metabolites that can act as biomarkers for glaucoma. According to PCA, fourteen regions of the NMR spectra were significant in explaining the metabolic variance between the glaucoma and control groups, with no differences found between POAG and NTG groups. These regions were further used in building a classifier for separating glaucoma from control patients, which achieved an AUC of 0.93. Peak integration was performed on these regions and a statistical analysis, after false discovery rate correction and adjustment for the different perioperative topical drug regimen, revealed that five of them were significantly different between groups. The glaucoma group showed a higher content in regions typical for betaine and taurine, possibly linked to neuroprotective mechanisms, and also a higher content in regions that are typical for glutamate, which can indicate damaged neurons and oxidative stress. These results show how aqueous humor metabolomics based on NMR spectroscopy can distinguish glaucoma patients from controls with a high accuracy. Further studies are needed to validate these results in order to incorporate them in clinical practice.

Efficacy, Safety, and Risk Factors for Failure of Standalone Ab Interno Gelatin Microstent Implantation versus Standalone Trabeculectomy.

PURPOSE: To compare the efficacy, safety, and risk factors for failure of standalone ab interno gelatin microstent implantation with mitomycin C (MMC) versus trabeculectomy with MMC. DESIGN: International, multicenter, retrospective interventional cohort study. PARTICIPANTS: Three hundred fifty-four eyes of 293 patients (185 microstent and 169 trabeculectomy) with no prior incisional surgery. METHODS: Consecutive eyes with uncontrolled glaucoma underwent microstent or trabeculectomy surgery from January 1, 2011 through July 31, 2015 at 4 academic ophthalmology centers: Toronto, Canada; Frankfurt, Germany; Salzburg, Austria; and Leuven, Belgium. MAIN OUTCOME MEASURES: Primary outcome measure was hazard ratio (HR) of failure, with failure defined as 2 consecutive intraocular pressure (IOP) readings of <6 mmHg with vision loss or >17 mmHg without glaucoma medications (complete success) at least 1 month after surgery despite in-clinic interventions (including needling). Secondary outcome measures included IOP thresholds of 6 to 14 mmHg and 6 to 21 mmHg and same thresholds allowing for medications (qualified success), interventions, complications, and reoperations. RESULTS: Baseline characteristics were similar, except more men (56% vs. 43%), younger patients (average, by 3 years), better preoperative visual acuity (22% vs. 32% with 0.4 logarithm of the minimum angle of resolution vision or worse), and more trabeculoplasty (52% vs. 30%) among microstent eyes. The adjusted HR of failure of the microstent relative to trabeculectomy was 1.2 (95% confidence interval [CI], 0.7-2.0) for complete success and 1.3 (95% CI, 0.6-2.8) for qualified success, and similar for other outcomes. Time to 25% failure was 11.2 months (95% CI, 6.9-16.1 months) and 10.6 months (95% CI, 6.8-16.2 months) for complete success and 30.3 months (95% CI, 19.0-∞ months) and 33.3 months (95% CI, 25.7-46.2 months) for qualified success. Overall, white ethnicity was associated with decreased risk of failure (adjusted HR, 0.49; 95% CI, 0.25-0.96), and diabetes was associated with increased risk of failure (adjusted HR, 4.21; 95% CI, 2.10-8.45). There were 117 and 165 distinct interventions: 43% and 31% underwent needling, respectively, and 50% of trabeculectomy eyes underwent laser suture lysis. There were 22 and 30 distinct complications, although most were transient. Ten percent and 5% underwent reoperation (P = 0.11). CONCLUSIONS: There was no detectable difference in risk of failure and safety profiles between standalone ab interno microstent with MMC and trabeculectomy with MMC.

The effect of glaucoma treatment using high-intensity focused ultrasound on total and corneal astigmatism: a prospective multicentre study.

PURPOSE: Ultrasound cycloplasty (UCP) acts through the selective coagulation of the ciliary body using high-intensity focused ultrasound (HIFU) technology. The aim of this study was to investigate whether the application of ultrasound beams targeting the ciliary body using an external probe influences astigmatism. METHODS: Multicentre, prospective, single-arm, open-label study in adult patients with primary open-angle glaucoma and moderately uncontrolled intraocular pressure (IOP) under glaucoma medication. The primary outcome was induced corneal astigmatism, calculated from topography, and assessed statistically through vector analysis. Secondary outcomes included induced total astigmatism and mean changes from baseline in best-corrected visual acuity (logMAR) and IOP. Subgroup analysis was performed to assess the impact of device centring on corneal and total induced astigmatism. RESULTS: Fifty eyes were enrolled. Mean age was 69.6 ± 11.3 years. At 1, 3 and 6 months postprocedure, HIFU-induced corneal astigmatism was 0.88 D × 93°, 0.87 D × 106° and 1.16 D × 97°, respectively, while induced total astigmatism was 0.62 D × 103°, 0.42 × 106° and 0.39 × 107°. By the last follow-up, the percentage of patients with <0.50, <1.00, <1.50 and <2.00 D of induced corneal versus total astigmatism was 8.3% versus 46%, 29% versus 66%, 62.5% versus 88% and 79% versus 94%. Visual acuity was statistically significantly impaired at 1 month, but no difference remained by 3 and 6 months postprocedure. CONCLUSION: Ultrasound cycloplasty procedure is associated with increased corneal astigmatism. However, its impact on total refractive astigmatism is less pronounced.

High-intensity Focused Ultrasound Cycloplasty: Analysis of Pupil Dynamics.

AIM: High-intensity focused ultrasound cystoplasty (UCP) aims to noninvasively and selectively target the ciliary body, thus lowering intraocular pressure (IOP). To be used on a large scale, the safety of the UCP procedure should be studied. Therefore, its effect on pupil behavior is important to better inform patients and to help physicians predict possible treatment side effects. This study aimed to evaluate to what extent UCP procedure (EyeOP-1®) affects pupil dynamics. MATERIALS AND METHODS: Consecutive glaucoma patients with uncontrolled IOP despite optimal medication scheduled for UCP treatment were recruited and followed for 6 months. Pupillometry (PlusoptiX® S04) was performed at baseline, and 1, 3 and 6 months after UCP procedure at scotopic and mesopic conditions. The difference between pupil diameter (PD) in both lighting conditions was calculated at the three follow-up visits. Demographic, clinical characteristics and specific ocular parameters (anterior chamber depth and volume, white-to-white measurement, axial length, phakic status) were registered. Statistical analysis was performed using STATA 14.1. RESULTS: Sixteen eyes of 16 patients with a mean age of 69 ± 11 years were included. Mean preoperative IOP and number of medications were 23.6 ± 3.0 mm Hg and 2.4 ± 1.3, respectively. Mean baseline scotopic and mesopic PD were 4.8 ± 0.8 mm and 4.4 ± 0.9 mm, respectively (difference = 0.38 ± 0.30 mm; range 0.1 to 1.2 mm). At month-1, the pupil diameter (PD) change between scotopic (4.6 ± 0.7 mm) and mesopic (4.5 ± 0.8 mm) conditions decreased to 0.03 ± 0.34 mm, p = 0.01. On the longer follow-up periods, however, the amplitude difference in PD compared to baseline was no longer significant (month-3: 0.28 ± 0.49 mm; month 6: 0.23 ± 0.41 mm; p >0.05). At the end of follow-up, mean scotopic and mesopic PD were 4.7 ± 1.0 mm and 4.4 ± 0.9 mm, respectively. CONCLUSION AND CLINICAL SIGNIFICANCE: In the early postoperative period after UCP treatment, most patients present with a less light-reactive pupil, which seems to normalize with time. HOW TO CITE THIS ARTICLE: Sousa DC, Ferreira NP, Marques-Neves C, Somers A, Vandewalle E, Stalmans I, Pinto LA. High-intensity Focused Ultrasound Cycloplasty: Analysis of Pupil Dynamics. J Curr Glaucoma Pract 2018;12(3):102-106.

The vitreopapillary interface in healthy and glaucoma: posterior vitreous detachment in the vitreopapillary interface study.

PURPOSE: To investigate the vitreopapillary interface (VPI) in health and glaucoma according to the different stages of posterior vitreous detachment (PVD) formation. METHODS: Prospective single centre study including healthy subjects and glaucoma patients. PVD staging was performed with spectral domain optical coherence tomography. Gender, age, lens status and refractive error were assessed in both groups. Glaucoma patients additionally had a comprehensive ophthalmological investigation including intraocular pressure measurement, visual field testing and confocal imaging of the optic nerve head. RESULTS: Data on 523 subjects (993 eyes) were included from the VPI study (clinicaltrials.gov NCT02290795) database (493 eyes of 258 healthy subjects and 500 eyes of 265 glaucoma patients). Healthy subjects were significantly younger than primary open angle glaucoma patients (59.7 ± 14.81 versus 70.0 ± 10.78 years, p < 0.001), but were otherwise matched for refractive error and gender. Significantly more glaucomatous eyes were pseudophakic (26.6% versus 5.1%). Including only phakic nonoperated eyes from subjects between 50 and 80 years old decreased the age difference between healthy and open angle glaucoma (64.1 ± 8.0 versus 65.9 ± 6.7 years, p = 0.051). Comparing these subgroups rendered similar average ages for PVD stages 0 and 4, in contrast to the significant older age for the glaucoma subgroup in stage 1 (64.1 ± 6.01 versus 61.4 ± 8.38 years, p < 0.001) and a trend towards significance in stage 3 (70.8 ± 69.8 versus 67.5 ± 5.92 years, p = 0.051). CONCLUSION: The VPI study is a large clinical trial investigating the VPI in health and glaucoma. A subset of glaucoma patients seems to experience stages 1-3 of PVD formation at older age compared to healthy subjects.

Standalone Ab Interno Gelatin Stent versus Trabeculectomy: Postoperative Interventions, Visual Outcomes, and Visits.

PURPOSE: To evaluate postoperative interventions, visual outcomes, and number of postoperative office visits after standalone ab interno gelatin microstent implantation with mitomycin C (MMC) vs. trabeculectomy with MMC. DESIGN: International, multicenter, retrospective cohort study. PARTICIPANTS: A total of 354 eyes of 293 patients, including 185 microstent eyes and 169 trabeculectomy eyes. METHODS: Consecutive eyes with uncontrolled glaucoma underwent microstent or trabeculectomy surgery from January 1, 2011, through July 31, 2015, at 4 academic ophthalmology centers: Toronto, Canada; Frankfurt, Germany; Salzburg, Austria; and Leuven, Belgium. MAIN OUTCOME MEASURES: Assessed outcomes included (1) in-clinic interventions, (2) transconjunctival needle revision (TCNR), (3) postoperative visits at 1 and 3 months, (4) >2 lines vision loss at last follow-up, (5) complete visual recovery, and (6) >0.5 or >1 diopter (D) of surgically induced astigmatism. RESULTS: Ninety-five (51.4%) of the microstent eyes and 105 (62.1%) of the trabeculectomy eyes underwent an intervention by last follow-up (log-rank P = 0.0004). The most common intervention was TCNR, followed by laser suture lysis. Seventy-eight (42.2%) microstent eyes and 55 (32.5%) trabeculectomy eyes received TCNR (adjusted hazard ratio [HR], 1.73 [95% confidence interval (CI), 1.10-2.71]): 128 total TCNRs in the microstent group and 95 in the trabeculectomy group. Predictors for TCNR included prior laser peripheral iridotomy and diabetes. Microstent eyes had on average 1.00 (standard deviation 2.32) fewer visits compared with trabeculectomy eyes in the first month (P < 0.001), adjusted for baseline characteristics. The percentage of eyes that had lost >2 lines of vision at last follow-up or reoperation was 12.4% (95% CI, 8.0%-18.7%) and was 21.9% (95% CI, 15.3%-30.1%) adjusted (P = 0.0383). A higher proportion of microstent eyes regained their baseline preoperative visual acuity compared with trabeculectomy eyes (log-rank P = 0.0250; adjusted HR, 1.46 [95% CI, 1.10-2.00]). Altogether, 25.3% (95% CI, 15.3%-38.9%) of microstent eyes and 40.7% (95% CI, 27.7%-55.3%) of trabeculectomy eyes had > 0.5 D surgically induced astigmatism on an adjusted basis; 8.0% (95% CI, 3.2%-18.6%) vs. 17.3% (95% CI, 8.9%-9.8%) had >1 D. CONCLUSIONS: Microstent eyes had more TCNRs (though fewer in-clinic interventions), fewer postoperative visits, and less vision loss, and experienced less surgically induced astigmatism, than trabeculectomy eyes. Overall, the postoperative course was less intensive for the microstent, except for more TCNRs.

Non-organic visual loss in children: prospective and retrospective analysis of associated psychosocial problems and stress factors.

PURPOSE: To report on the prevalence of non-organic visual loss (NOVL) and its associated psychopathology and psychosocial stress factors on children presenting with visual problems without an obvious cause at a routine ophthalmological examination. METHODS: One hundred and seventy children presented at our paediatric ophthalmology department between 2007 and 2014 with visual loss. Routine examination showed no obvious underlying cause. Pattern-onset visual-evoked potentials (pVEPs) were performed to obtain an objective visual assessment. Selected patients underwent more investigations, and follow-up was organized in every child to differentiate organic visual loss (OVL) from NOVL. In the NOVL group, we retrospectively analysed the medical file data and prospectively the questionnaires completed by patients and their parents. RESULTS: Eighty-five children (50%) were diagnosed with OVL, the other 50% of children were diagnosed with NOVL. In the latter, girls predominated and the mean age was 11.0 years. The most common presenting symptom was binocular reduced visual acuity. pVEPs were normal in all patients. We categorized associated comorbidity in the NOVL group in three subgroups: malingering, psychosocial stressors and child psychiatric disorders. CONCLUSION: Non-organic visual loss in children is a common diagnosis in clinical practice. The diagnosis is made by recognition of characteristic features and by exclusion of organic disease. pVEP is a useful tool to obtain an objective visual acuity and to differentiate functional from organic vision loss. The prognosis in NOVL is good with a spontaneous recovery in the majority of patients. Ophthalmologists should be aware of possible underlying psychosocial and psychiatric disorders; referral can be necessary.