Treatment Outcomes Comparing the Paul and Baerveldt Glaucoma Implants After One Year of Follow-Up.

PRCIS: In reducing intraocular pressure (IOP), Paul (PGI) and Baerveldt (BGI) glaucoma implants are safe and effective in patients with glaucoma. OBJECTIVE: To compare efficacy and safety profiles of the PGI and BGI in the treatment of medically uncontrolled glaucoma at 1 year of follow-up. METHODS: Retrospective analysis of patients implanted with a PGI or BGI with a minimum of 12 months follow-up. The primary outcome was surgical success defined as IOP ≥6 and ≤18 mm Hg and at least 20% IOP reduction from baseline. Secondary outcomes included IOP measurements, number of medications, and complications. RESULTS: Twenty-three patients implanted with PGI and 27 with BGI were included. At last visit (12 mo), mean IOP had decreased from 23.7 ± 6.9 to 0.1 ± 2.9 mm Hg in the PGI group versus 26 ± 7.3 to 10.4 ± 4.9 mm Hg with the BGI ( P < 0.001 for both comparisons). Overall qualified success rates were similar between groups (PGI 91% vs BGI 89%, P = 0.784). IOP was significantly lower in the PGI at week 1 and month 1 of follow-up versus the BGI (13.6 ± 6.1 vs 20.1 ± 7.4; 14.6±3.8 vs 21.2 ± 5.8 mm Hg; P < 0.002 for both) with a lower number of medications (1.57 ± 1.47 vs 2.52 ± 1.16 at mo 1, P = 0.015). Most complications were minor and similar in both groups. CONCLUSION: Both PGI and BGI are safe and effective in reducing IOP in patients with glaucoma, with similar success rates.

The effect of citicoline oral solution on quality of life in patients with glaucoma: the results of an international, multicenter, randomized, placebo-controlled cross-over trial.

PURPOSE: This study aims to evaluate whether the use of citicoline oral solution could improve quality of life in patients with chronic open-angle glaucoma (OAG). DESIGN: Randomized, double-masked, placebo-controlled, cross-over study was used. Patients were randomized to one of the two sequences: either citicoline 500 mg/day oral solution-placebo or placebo-citicoline 500 mg/day oral solution. Switch of treatments was done after 3 months; patients were then followed for other 6 months. Follow-up included 3-month, 6-month, and 9-month visits. OUTCOMES: The primary outcome was the mean change of "intra-patient" composite score of the Visual Function Questionnaire-25 (VFQ-25). after citicoline oral solution vs placebo at 6-month visit as compared with baseline. METHODS: The trial was multicenter, conducted at 5 European Eye Clinics. OAG patients with bilateral visual field damage, a mean deviation (MD) ranging from - 5 to - 13 dB in the better eye, and controlled IOP were included. VFQ-25 and SF-36 questionnaires were administered at baseline and at 3-, 6-, and 9-month visits. A mixed effect model, with a random effect on the intercept, accounted for correlations among serial measurements on each subject. RESULTS: The primary pre-specified outcome of the analysis reached statistical significance (p = 0.0413), showing greater improvement after citicoline oral solution. There was an increase in the composite score in both arms compared to baseline, but it was significant only for the placebo-citicoline arm (p = 0.0096, p = 0.0007, and p = 0.0006 for the three time-points compared to baseline). The effect of citicoline was stronger in patients with vision-related quality of life more affected by glaucoma at baseline. CONCLUSIONS: This is the first placebo-controlled clinical study evaluating the effect of a medical treatment aiming at improving vision-related quality of life in glaucomatous patients.

The Effects of Intranasal, Inhaled and Systemic Glucocorticoids on Intraocular Pressure: A Literature Review.

Topical glucocorticoids are a well-known risk factor of intraocular pressure (IOP) elevation in one third of the general population and in up to 90% of glaucomatous patients. Whether this steroid response is caused by intranasal, inhaled or systemic glucocorticoids, is less known. This study presents an overview of the current literature on the topic, thereby providing guidance on when ophthalmological follow-up is indicated. A literature study was performed in Medline, and 31 studies were included for analysis. Twelve out of fourteen studies discussing intranasal glucocorticoids show no significant association with an elevated IOP. Regarding inhaled glucocorticoids, only three out of twelve studies show a significant association. The observed increase was either small or was only observed in patients treated with high inhaled doses or in patients with a family history of glaucoma. An elevated IOP caused by systemic glucocorticoids is reported by four out of the five included studies, with one study reporting a clear dose-response relationship. This review concludes that a steroid response can be triggered in patients treated with systemic glucocorticoids. Inhaled glucocorticoids may cause a significant IOP elevation when administered in high doses or in patients with a family history of glaucoma. At present, there is no evidence for a clinically significant steroid response caused by intranasally administered glucocorticoids.

Management of Childhood Glaucoma Following Cataract Surgery.

Glaucoma remains a frequent serious complication following cataract surgery in children. The optimal approach to management for 'glaucoma following cataract surgery' (GFCS), one of the paediatric glaucoma subtypes, is an ongoing debate. This review evaluates the various management options available and aims to propose a clinical management strategy for GFCS cases. A literature search was conducted in four large databases (Cochrane, PubMed, Embase, and Web of Science), from 1995 up to December 2021. Thirty-nine studies-presenting (1) eyes with GFCS; a disease entity as defined by the Childhood Glaucoma Research Network Classification, (2) data on treatment outcomes, and (3) follow-up data of at least 6 months-were included. Included papers report on GFCS treated with angle surgery, trabeculectomy, glaucoma drainage device implantation (GDD), and cyclodestructive procedures. Medical therapy is the first-line treatment in GFCS, possibly to bridge time to surgery. Multiple surgical procedures are often required to adequately control GFCS. Angle surgery (360 degree) may be considered before proceeding to GDD implantation, since this technique offers good results and is less invasive. Literature suggests that GDD implantation gives the best chance for long-term IOP control in childhood GFCS and some studies put this technique forward as a good choice for primary surgery. Cyclodestruction seems to be effective in some cases with uncontrolled IOP. Trabeculectomy should be avoided, especially in children under the age of one year and children that are left aphakic. The authors provide a flowchart to guide the management of individual GFCS cases.

Ultrasound Cyclo Plasty for Treatment of Surgery-Naïve Open-Angle Glaucoma Patients: A Prospective, Multicenter, 2-Year Follow-Up Trial.

BACKGROUND: The purpose of this prospective study was to evaluate the efficacy and safety of the Ultrasound Cyclo Plasty (UCP) procedure using high-intensity focused ultrasound in surgery-naïve open-angle glaucoma patients. METHODS: prospective, non-randomized, single-arm, multicenter clinical trial. Sixty-six eyes with primary open-angle glaucoma, intraocular pressure (IOP) ≥21 mmHg and with no history of filtering surgery were enrolled. Patients were treated by UCP with a therapy probe comprising six piezoelectric transducers, consecutively activated for 8 s each. Complete ophthalmic examination was performed before the procedure, 1 day after the procedure, and 1, 3, 6, 12, 18 and 24 months after the procedure. Primary outcomes were complete success (defined as IOP lowering from baseline ≥20% without additional glaucoma medications) and vision-threatening complications. Secondary outcomes were the presence of complications and the reduction of the number of medications used. RESULTS: IOP was significantly reduced after one procedure (p < 0.05), from a mean pre-operative value of 24.3 ± 2.9 mmHg (n = 2.3 hypotensive medications) to a mean value of 15.9 ± 3.6 mmHg (n = 2.2 hypotensive medications) at 2 years (mean IOP lowering of 33%). Surgical success was achieved in 74% of eyes. Notwithstanding side effects such as transient anterior chamber inflammation, refractive error changes, transient hypotony and macular edema, no major intra or post-operative complications such as phthisis, induced cataract, neovascularization or significant vision loss were observed. CONCLUSIONS: Ultrasound Cyclo Plasty is a valuable, effective and well-tolerated procedure to lower IOP in patients with open-angle glaucoma without previous filtering surgery.

Comparison of preserved bimatoprost 0.01% with preservative-free tafluprost: A randomised, investigator-masked, 3-month crossover, multicentre trial, SPORT II.

IMPORTANCE: This study compares the efficacy and tolerability of a preservative-free prostaglandin analogue (tafluprost 15 mg/ml) to a prostaglandin analogue that uses 0.02% of benzalkonium chloride (bimatoprost 0.1 mg/ml). BACKGROUND: Different prostaglandin analogues have been commercially approved, with differences in tolerability. DESIGN: Prospective, randomised, investigator-masked, 3-month crossover, multicentre trial. PARTICIPANTS: Sixty-four patients with ocular hypertension or open-angle glaucoma were randomised to two groups, after a 4-week washout period from their current topical drop regimen. METHODS: Participants were randomised to tafluprost (Group 1; n = 33) or bimatoprost (Group 2; n = 31). At month 3, each group switched to the opposite treatment. IOP was evaluated at multiple timepoints. MAIN OUTCOME MEASURES: The primary outcome was difference in mean IOP between the two groups at the final visit. Secondary outcomes included change from baseline IOP at month 3 and month 6, difference in mean IOP at month 3 and difference in IOP at all timepoints. Safety outcomes included best-corrected visual acuity (BCVA), adverse events, ocular tolerability, optic nerve assessment and slit lamp biomicroscopy. RESULTS: Both medications significantly lowered IOP at month 6 compared to baseline: 5.4 mmHg (27%) for tafluprost and 6.8 mmHg (33%) for bimatoprost (p < 0.0001). No significant differences in any of the safety measures (including conjunctival hypearemia) were detected. CONCLUSIONS AND RELEVANCE: Bimatoprost produced a statistically significant greater IOP reduction compared to tafluprost with minimal to no difference in side effects. This should be borne in mind when weighing up the pros and cons of preserved versus preservative-free prostaglandin analogue therapy. CLINICALTRIALS.GOV IDENTIFIER: NCT02471105.

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.

Safety and Efficacy of a Preservative-Free Artificial Tear Containing Carboxymethylcellulose and Hyaluronic Acid for Dry Eye Disease: A Randomized, Controlled, Multicenter 3-Month Study.

PURPOSE: To compare the efficacy and safety of an artificial tear combining the polymers carboxymethylcellulose (CMC) and hyaluronic acid (HA), to a formulation of CMC alone in subjects with dry eye. METHODS: A preservative-free artificial tear (CMC-HA) was compared with an existing artificial tear (CMC). Subjects with mild-to-severe signs and symptoms of dry eye were enrolled in this double-masked, randomized, multicenter trial, and dosed at least twice daily for 90 days, with follow-up visits at Days 7, 30, 60, and 90. Ocular Surface Disease Index (OSDI) was the primary outcome measure. Secondary outcome measures were tear break-up time (TBUT), ocular surface staining, Schirmer test with anesthesia, and visual analog scale (VAS) scores of dry eye symptom severity and formulation acceptability. Safety measures included adverse events, biomicroscopy, and visual acuity. RESULTS: A total of 460 subjects were enrolled across 45 sites (38 in Europe; 7 in Australia), of whom 454 were randomized to receive treatment. The per-protocol (PP) population consisted of 394 subjects, 364 (92.4%) of whom completed the study. In the PP population, the mean ± SD change from baseline in OSDI score at the primary timepoint, Day 90, was -16.9±17.5 for CMC-HA and -16.0±16.1 for CMC. CMC-HA was non-inferior to CMC based upon a confidence interval method. Both treatments significantly improved (P<0.001) OSDI, symptom VAS scores, TBUT, and ocular surface staining from baseline at all follow-up visits, with minimal differences between groups. Greater reduction of overall ocular pain/discomfort was reported in subjects using CMC-HA versus CMC (P=0.048). Approximately 10% of subjects in each group reported treatment-related adverse events of generally mild to moderate severity. CONCLUSION: The new CMC-HA formulation was effective and well tolerated, and demonstrates a greater potential for symptom relief compared with CMC. These data support implementation of this formula for the management of dry eye patients.

A Retrospective Case Series of Uveal Effusion Syndrome.

PURPOSE: This study aimed to describe the clinical findings and management of eyes affected by uveal effusion syndrome. METHODS: We retrospectively evaluated the charts of 13 eyes of 8 consecutive patients diagnosed with uveal effusion syndrome attending the Ophthalmology Unit of the University Hospitals Leuven, Belgium, between 2007 and 2018. The presenting features, investigations, management, and outcomes were analyzed for each case. RESULTS: Cataract surgery was the predisposing factor for uveal effusion in 6 eyes, 2 bilateral uveal effusions (4 eyes) were considered to be medication-induced, and in 3 eyes, the uveal effusion was described as idiopathic. Fundus examination of 5 of 13 eyes showed bullous choroidal detachment, treated with pars plana vitrectomy with superotemporal sclerectomy or transscleral punction. Fundoscopy showed uveal effusion without serous retinal detachment in 3 eyes. Serous retinal detachment accompanied by uveal swelling was observed in 3 eyes and the 2 remaining eyes presented with uveal swelling only. The 8 nonbullous choroidal detachments were treated in a conservative way. A rapid resolution of subretinal fluid and uveal effusion was observed in all cases. CONCLUSIONS: A conservative approach with acetazolamide treatment or just observation was used in our case series in choroidal detachment without substantial visual loss if, over time, slow improvement was documented. However, further studies are needed to verify the effectiveness of the reported therapy.

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.

Accurate prediction of glaucoma from colour fundus images with a convolutional neural network that relies on active and transfer learning.

PURPOSE: To assess the use of deep learning (DL) for computer-assisted glaucoma identification, and the impact of training using images selected by an active learning strategy, which minimizes labelling cost. Additionally, this study focuses on the explainability of the glaucoma classifier. METHODS: This original investigation pooled 8433 retrospectively collected and anonymized colour optic disc-centred fundus images, in order to develop a deep learning-based classifier for glaucoma diagnosis. The labels of the various deep learning models were compared with the clinical assessment by glaucoma experts. Data were analysed between March and October 2018. Sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and amount of data used for discriminating between glaucomatous and non-glaucomatous fundus images, on both image and patient level. RESULTS: Trained using 2072 colour fundus images, representing 42% of the original training data, the trained DL model achieved an AUC of 0.995, sensitivity and specificity of, respectively, 98.0% (CI 95.5%-99.4%) and 91% (CI 84.0%-96.0%), for glaucoma versus non-glaucoma patient referral. CONCLUSIONS: These results demonstrate the benefits of deep learning for automated glaucoma detection based on optic disc-centred fundus images. The combined use of transfer and active learning in the medical community can optimize performance of DL models, while minimizing the labelling cost of domain-specific mavens. Glaucoma experts are able to make use of heat maps generated by the deep learning classifier to assess its decision, which seems to be related to inferior and superior neuroretinal rim (within ONH), and RNFL in superotemporal and inferotemporal zones (outside ONH).

Retinal oximetry: Metabolic imaging for diseases of the retina and brain.

Retinal oximetry imaging of retinal blood vessels measures oxygen saturation of hemoglobin. The imaging technology is non-invasive and reproducible with remarkably low variability on test-retest studies and in healthy cohorts. Pathophysiological principles and novel biomarkers in several retinal diseases have been discovered, as well as possible applications for systemic and brain disease. In diabetic retinopathy, retinal venous oxygen saturation is elevated and arteriovenous difference progressively reduced in advanced stages of retinopathy compared with healthy persons. This correlates with pathophysiology of diabetic retinopathy where hypoxia stimulates VEGF production. Laser treatment and vitrectomy both improve retinal oximetry values, which correlate with clinical outcome. The oximetry biomarker may allow automatic measurement of severity of diabetic retinopathy and predict its response to treatment. Central retinal vein occlusion is characterized by retinal hypoxia, which is evident in retinal oximetry. The retinal hypoxia seen on oximetry correlates with the extent of peripheral ischemia, visual acuity and thickness of macular edema. This biomarker may help diagnose and measure severity of vein occlusion and degree of retinal ischemia. Glaucomatous retinal atrophy is associated with reduced oxygen consumption resulting in reduced arteriovenous difference and higher retinal venous saturation. The oximetry findings correlate with worse visual field, thinner nerve fiber layer and smaller optic disc rim. This provides an objective biomarker for glaucomatous damage. In retinitis pigmentosa, an association exists between advanced atrophy, worse visual field and higher retinal venous oxygen saturation, lower arteriovenous difference. This biomarker may allow measurement of severity and progression of retinitis pigmentosa and other atrophic retinal diseases. Retinal oximetry offers visible light imaging of systemic and central nervous system vessels. It senses hypoxia in cardiac and pulmonary diseases. Oximetry biomarkers have been discovered in Alzheimer's disease and multiple sclerosis and oxygen levels in the retina correspond well with brain.

Heterogeneity in arterial hypertension and ocular perfusion pressure definitions: Towards a consensus on blood pressure-related parameters for glaucoma studies.

PURPOSE: Glaucoma studies have long taken into account the blood pressure (BP) status of patients. This study summarizes and evaluates the impact of the different criteria that have been used for BP-related variables in glaucoma research. METHODS: Studies included in two meta-analyses that reviewed the role of BP in glaucoma were analyzed. Additional studies published after the search periods of the meta-analyses were also included. Criteria for the definition of arterial hypertension and other BP-related variables, such as mean arterial pressure (MAP) and mean ocular perfusion pressure (MOPP), were retrieved. RESULTS: Sixty-four studies were evaluated. One-third used 140 mmHg as a systolic BP cut-off to define hypertension, 20% used 160 mmHg and the remaining half used various other criteria. Less than 20% of studies reported MAP and/or MOPP. While eight of the ten studies reporting MAP used a correct formula that only happened for five of the eleven studies reporting MOPP. Using as an example average blood pressure values, incorrectly used formulas could have led to an overestimation of more than 100% of the expected values. CONCLUSION: Considerable heterogeneity exists in BP-related variables in glaucoma research and different definitions can lead to large disparities. Glaucoma research would benefit from a consensus regarding blood pressure parameters.

Retinal oxygen saturation as a non-invasive estimate for mixed venous oxygen saturation and cardiac output.

PURPOSE: To investigate the correlation between retinal vessel oxygen saturation and mixed venous oxygen saturation (SvO2-mixed ) and cardiac output (CO). METHODS: Retinal arterial (SaO2-retinal ) and venous (SvO2-retinal ) oxygen saturation were measured non-invasively with dual-wavelength retinal oximetry in subjects receiving invasive measurements of SvO2-mixed and CO through right heart catheterization. Correlations were analysed using Spearman's rank correlation coefficients and linear regression models. RESULTS: Fourteen patients (median age 62.7 years, range: 21-77) were included in the analysis. When adjusted for age, SvO2-retinal showed a positive correlation with SvO2-mixed (ß = 0.80, p = 0.003). Retinal arteriovenous oxygen saturation difference was significantly correlated with the inverse of CO (Spearman's ρ = 0.59, p = 0.026). CONCLUSION: This pilot study provides proof of concept for the use of retinal oximetry as a non-invasive tool to assess systemic cardiovascular function.

Improved discrimination between normal-tension and primary open-angle glaucoma with advanced vascular examinations - the Leuven Eye Study.

PURPOSE: Vascular factors have been suggested to influence the development and progression of glaucoma. They are thought to be especially relevant for normal-tension glaucoma (NTG) patients. We aim to investigate which vascular factors, including advanced vascular examinations, better describe patients with NTG comparing to those with primary open-angle glaucoma (POAG). METHODS: The Leuven Eye Study database (182 NTG and 202 POAG patients; similar structural and functional damage) was used to compute three multivariate logistic regression models: a conventional model (conventional parameters only, including vascular-related self-reported phenomena, such as migraine or peripheral vasospasm); an advanced vascular model (advanced vascular parameters only: colour Doppler imaging (CDI), retinal oximetry, ocular pulse amplitude and choroidal thickness); and a global model, in which both types of parameters were allowed. Receiver operating characteristic (ROC) curves and corresponding areas under the curve (AUC) were calculated and compared between models. RESULTS: Patients with NTG had a higher resistive index and lower early systolic acceleration (ESA) in their retrobulbar vessels and a smaller arteriovenous retinal oxygen saturation difference. The global model (AUC 0.743) showed a significantly better discriminative ability when compared to either the conventional (AUC 0.687, p = 0.049) or the advanced vascular (AUC 0.677, p = 0.005) models. Also, the conventional and the advanced vascular models showed a similar discriminative ability (p = 0.823). CONCLUSION: Patients with NTG have more signs of vascular dysfunction. Clinical conventional parameters, such as asking simple vascular-related questions, combined with advanced vascular examinations provide information to better understand the value that non-IOP-related factors play in NTG.

Semi-automated kinetic perimetry: Comparison of the Octopus 900 and Humphrey visual field analyzer 3 versus Goldmann perimetry.

PURPOSE: To evaluate the clinical usefulness and reproducibility of (semi-)automated kinetic perimetry of the Octopus 900 and Humphrey field analyzer 3 (HFA3) compared to Goldmann perimetry as reference technique. METHODS: A prospective interventional study of two study groups, divided into three subgroups. The first study group consisted of 28 patients, performing one visual field examination on each of the three devices. A second group of 30 patients performed four examinations, one on Goldmann and three on Octopus 900 with the following testing strategies: (1) with reaction time (RT) vector, no headphone; (2) without RT vector, no headphone; and (3) without RT vector, with headphone. Comparisons for V4e and I4e stimuli were made of the mean isopter radius (MIR) and of the distances of the isopter to the central visual axis in four directions. Statistical analysis was made with the R software version 3.2.2. RESULTS: For V4e stimuli, the mean isopter radius showed no statistic significant difference comparing Goldmann to HFA3 [p-value = 0.144; confidence interval (CI) -0.152 to 0.019] and comparing Goldmann to Octopus 900 without RT vector, either with (p-value = 0.347; CI -0.023 to 0.081) or without headphone (p-value = 0.130; CI -0.011 to 0.095). Octopus 900 with RT vector produced a significantly larger MIR for V4e stimuli in comparison to Goldmann (p-value < 0.001). I4e stimuli produced statistically significantly larger visual field areas when comparing HFA3 and Octopus 900 to Goldmann perimetry. CONCLUSION: Humphrey field analyzer 3 and Octopus 900 without RT vector are promising successors of Goldmann perimetry.

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.

New Normative Database of Inner Macular Layer Thickness Measured by Spectralis OCT Used as Reference Standard for Glaucoma Detection.

PURPOSE: This study examines the capacity to detect glaucoma of inner macular layer thickness measured by spectral-domain optical coherence tomography (SD-OCT) using a new normative database as the reference standard. METHODS: Participants (N = 148) were recruited from Leuven (Belgium) and Zaragoza (Spain): 74 patients with early/moderate glaucoma and 74 age-matched healthy controls. One eye was randomly selected for a macular scan using the Spectralis SD-OCT. The variables measured with the instrument's segmentation software were: macular nerve fiber layer (mRNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) volume and thickness along with circumpapillary RNFL thickness (cpRNFL). The new normative database of macular variables was used to define the cutoff of normality as the fifth percentile by age group. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) of each macular measurement and of cpRNFL were used to distinguish between patients and controls. RESULTS: Overall sensitivity and specificity to detect early-moderate glaucoma were 42.2% and 88.9% for mRNFL, 42.4% and 95.6% for GCL, 42.2% and 94.5% for IPL, and 53% and 94.6% for RNFL, respectively. The best macular variable to discriminate between the two groups of subjects was outer temporal GCL thickness as indicated by an AUROC of 0.903. This variable performed similarly to mean cpRNFL thickness (AUROC = 0.845; P = 0.29). CONCLUSIONS: Using our normative database as reference, the diagnostic power of inner macular layer thickness proved comparable to that of peripapillary RNFL thickness. TRANSLATIONAL RELEVANCE: Spectralis SD-OCT, cpRNFL thickness, and individual macular inner layer thicknesses show comparable diagnostic capacity for glaucoma and RNFL, GCL, and IPL thickness may be useful as an alternative diagnostic test when the measure of cpRNFL shows artifacts.

Non-invasive assessment of cerebral oxygenation: A comparison of retinal and transcranial oximetry.

BACKGROUND: To investigate the correlation between cerebral (SO2-transcranial), retinal arterial (SaO2-retinal) and venous (SvO2-retinal) oxygen saturation as measured by near-infrared spectroscopy (NIRS) and retinal oximetry respectively. METHODS: Paired retinal and cerebral oxygen saturation measurements were performed in healthy volunteers. Arterial and venous retinal oxygen saturation and diameter were measured using a non-invasive spectrophotometric retinal oximeter. Cerebral oxygen saturation was measured using near-infrared spectroscopy. Correlations between SO2-transcranial and retinal oxygen saturation and diameter measurements were assessed using Pearson correlation coefficients. Lin's concordance correlation coefficient (CCC) and Bland-Altman analysis were performed to evaluate the agreement between SO2-transcranial as measured by NIRS and as estimated using a fixed arterial:venous ratio as 0.3 x SaO2-retinal + 0.7 x SvO2-retinal. The individual relative weight of SaO2-retinal and SvO2-retinal to obtain the measured SO2-transcranial was calculated for all subjects. RESULTS: Twenty-one healthy individuals aged 26.4 ± 2.2 years were analyzed. SO2-transcranial was positively correlated with both SaO2-retinal and SvO2-retinal (r = 0.44, p = 0.045 and r = 0.43, p = 0.049 respectively) and negatively correlated with retinal venous diameter (r = -0.51, p = 0.017). Estimated SO2-transcranial based on retinal oximetry showed a tolerance interval of (-13.70 to 14.72) and CCC of 0.46 (95% confidence interval: 0.05 to 0.73) with measured SO2-transcranial. The average relative weights of SaO2-retinal and SvO2-retinal to obtain SO2-transcranial were 0.31 ± 0.11 and 0.69 ± 0.11, respectively. CONCLUSION: This is the first study to show the correlation between retinal and cerebral oxygen saturation, measured by NIRS and retinal oximetry. The average relative weight of arterial and venous retinal oxygen saturation to obtain the measured transcranial oxygen saturation as measured by NIRS, approximates the established arterial:venous ratio of 30:70 closely, but shows substantial inter-individual variation. These findings provide a proof of concept for the role of retinal oximetry in evaluating cerebral oxygenation.

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.