Is Hyperopia an Important Risk Factor for PACG in the Dutch Population?—A Case Control Study

Objectives. To determine if hyperopia is a risk factor for primary angle-closure glaucoma (PACG) in the Dutch population and to identify other biometrical parameters as risk factors for PACG including axial length (AL), anterior chamber depth (ACD), and k values. Methods. The study population consisted of PACG patients that had undergone a laser peripheral iridotomy (LPI). The control group consisted of age- and gender-matched cataract patients. The main outcome was hyperopia (spherical equivalent ≥+0.5 dioptres) measured with IOL Master or autorefractor. Refractive error, ACD, AL, and k values were tested with a Mann-Whitney U test and by logistic regression. Results. 117 PACG patients and 234 controls were included (mean age = 80 years ± 3.6). The prevalence of hyperopia in patients and controls was 69.6% and 61.1%, respectively (Fisher’s test P=0.076). Mann-Whitney U test showed no statistically significant relation with refractive error (P=0.068) or k values (P=0.607). In contrast, ACD and AL were statistically significant (P<0.001). Tested with logistic regression, only ACD was a significant predictor of PACG (P<0.001). Conclusion. There was no statistically significant correlation between refractive error and PACG. ACD was strongly correlated, though, with PACG, whereas AL turned out to be a less significant risk factor

Predicting visual function from the measurements of retinal nerve fiber layer structure

Purpose: To develop and validate a method for predicting visual function from retinal nerve fibre layer (RNFL) structure in glaucoma. Methods: RNFL thickness (RNFLT) measurements from GDxVCC scanning laser polarimetry (SLP) and visual field (VF) sensitivity from standard automated perimetry were made available from 535 eyes from three centres. In a training dataset, structure-function relationships were characterized using linear regression and a type of neural network: Radial Basis Function customised under a Bayesian framework (BRBF). These two models were used in a test dataset to 1) predict sensitivity values at individual VF locations from RNFLT measurements and 2) predict the spatial relationship between VF locations and positions at a peripapillary RNFLT measurement annulus. Predicted spatial relationships were compared with a published anatomical structure-function map. Results: Compared with linear regression, BRBF yielded a nearly two-fold improvement (P<0.001; paired t-test) in performance of predicting VF sensitivity in the test dataset (mean absolute prediction error of 2.9dB (standard deviation (SD) 3.7dB) versus 4.9dB (SD 4.0dB)). The predicted spatial structure-function relationship accorded better (P<0.001; paired t-test) with anatomical prior knowledge when the BRBF was compared with the linear regression (median absolute angular difference of 15° versus 62°). Conclusions: The BRBF generates clinically useful relationships that relate topographical maps of RNFL measurement to VF locations and allows the VF sensitivity to be predicted from structural measurements. This method may allow clinicians to evaluate structural and functional measures in the same domain. It could also be generalized to use other structural measures

Progression Detection of Glaucoma from Polarimetric Images

Detecting glaucoma progression is crucial for assessing the effectivity of the treatment. This paper describes three methods for detecting progression related changes in polarimetric images of the retinal nerve fiber layer (NFL), both on a global and on a local scale. Detecting global changes proved not to be feasible due to poor reproducibility of the measurements at the pixel level. Local progression on the other hand could be detected. A distribution based approach did not work, but locating specific areas with minimum size and minimum NFL decrease did give relevant results. The described algorithm yielded a TPR of 0.42 and an FPR of 0.095 on our datasets. It proved to be able to outline suspect areas that show NFL reductio

Differences in clinical presentation of primary open-angle glaucoma between African and European populations

PURPOSE: Primary open‐angle glaucoma (POAG) has been reported to occur more frequently in Africans, and to follow a more severe course compared to Europeans. We aimed to describe characteristics of POAG presentation and treatment across three ethnic groups from Africa and one from Europe. METHODS: We ascertained 151 POAG patients from South African Coloured (SAC) and 94 South African Black (SAB) ethnicity from a university hospital in South Africa. In Tanzania, 310 patients were recruited from a university hospital and a referral hospital. In the Netherlands, 241 patients of European ancestry were included. All patients were over 35 years old and had undergone an extensive ophthalmic examination. Patients were diagnosed according to the ISGEO criteria. A biogeographic ancestry analysis was performed to estimate the proportion of genetic African ancestry (GAA). RESULTS: The biogeographic ancestry analysis showed that the median proportion of GAA was 97.6% in Tanzanian, 100% in SAB, 34.2% in SAC and 1.5% in Dutch participants. Clinical characteristics at presentation for Tanzanians, SAB, SAC and Dutch participants, respectively: mean age: 63, 57, 66, 70 years (p < 0.001); visual acuity in the worse eye: 1.78, 1.78, 0.3, 0.3 LogMAR (p < 0.001); maximum intraocular pressure of both eyes: 36, 34, 29, 29 mmHg (p (anova)  < 0.001); maximum vertical cup to disc ratio (VCDR) of both eyes: 0.90, 0.90, 0.84, 0.83 (p < 0.001); mean central corneal thickness: 506, 487, 511, 528 μm (p < 0.001). Fourteen percent of Tanzanian patients presented with blindness (<3/60 Snellen) in the better eye in contrast to only 1% in the Dutch. CONCLUSION: In this multi‐ethnic comparative study, Sub‐Saharan Africans present at a younger age with lower visual acuity, higher IOP, larger VCDR, than SAC and Dutch participants. This indicates the more progressive and destructive course in Sub‐Saharan Africans

A Novel Redox Method for Rapid Production of Functional Bi-Specific Antibodies For Use in Early Pilot Studies

We demonstrate here a rapid alternative method for the production of functional bi-specific antibodies using the mild reducing agent 2-mercaptoethanesulfonic acid sodium salt (MESNA). Following reduction of a mixture of two monoclonal antibodies with MESNA to break inter heavy chain bonds, this solution is dialysed under oxidising conditions and antibodies are allowed to reform. During this reaction a mixture of antibodies is formed, including parental antibodies and bi-specific antibody. Bi-specific antibodies are purified over two sequential affinity columns. Following purification, bi-specificity of antibodies is determined in enzyme-linked immunosorbent assays and by flow cytometry. Using this redox method we have been successful in producing hybrid and same-species bi-specific antibodies in a time frame of 6–10 working days, making this production method a time saving alternative to the time-consuming traditional heterohybridoma technology for the production of bi-specific antibodies for use in early pilot studies. The use of both rat and mouse IgG antibodies forming a rat/mouse bi-specific antibody as well as producing a pure mouse bi-specific antibody and a pure rat bi-specific antibody demonstrates the flexibility of this production method

Perceptual judgment and saccadic behavior in a spatial distortion with briefly presented stimuli.

When observers are asked to localize the peripheral position of a small probe with respect to the mid-position of a spatially extended comparison stimulus, they tend to judge the probe as being more peripheral than the mid-position of the comparison stimulus. This relative mislocalization seems to emerge from differences in absolute localization, that is the comparison stimulus is localized more towards the fovea than the probe. The present study compared saccadic behaviour and relative localization judgements in three experiments and determined the quantitative relationship between both measures. The results showed corresponding effects in localization errors and saccadic behaviour. Moreover, it was possible to estimate the amount of the relative mislocalization by means of the saccadic amplitude

Treatment of Open-Angle Glaucoma and Ocular Hypertension with Preservative-Free Tafluprost/Timolol Fixed-Dose Combination Therapy : The VISIONARY Study

Funding Information: Funding was provided by Santen SA for the study, medical writing services and Rapid Service Fees. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. The contribution of IRCCS Fondazione Bietti to this work was supported by the Italian Ministry of Health and by Fondazione Roma. Publisher Copyright: © 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Introduction: A non-interventional, multicenter, European, prospective evaluation of the effectiveness, tolerability, and safety of a topical preservative-free tafluprost (0.0015%) and timolol (0.5%) fixed-dose combination (PF tafluprost/timolol FC) in adults with open-angle glaucoma (OAG) and ocular hypertension (OHT) demonstrating insufficient response to topical beta-receptor blockers or prostaglandin analogue (PGA) monotherapy. Methods: Mean intraocular pressure (IOP) change from baseline was measured at study visits following a switch to PF tafluprost/timolol FC. Primary endpoint was absolute mean IOP change at month 6. Change from baseline concerning ocular signs and symptoms was also explored. Results: Analyses included 577 patients (59.6% female). Mean age (SD) was 67.8 (11.67) years. Mean (SD) IOP reduction from baseline was significant at all study visits; 5.4 (3.76) mmHg (23.7%) at week 4, 5.9 (3.90) mmHg (25.6%) at week 12, and 5.7 (4.11) mmHg (24.9%) at month 6 (p < 0.0001 for all visits). At month 6, 69.2%, 53.6%, 40.0%, and 25.8% were responders based on ≥ 20%, ≥ 25%, ≥ 30%, and ≥ 35% cutoff values for mean IOP, respectively. Significant reductions were observed concerning corneal fluorescein staining (p < 0.0001), dry eye symptoms, irritation, itching, and foreign body sensation (p < 0.001 for each parameter). Conjunctival hyperemia was significantly reduced at all study visits (p < 0.0001 at each visit). Overall, 69 treatment-related adverse events (AEs) were reported, one of which was serious (status asthmaticus). Most AEs were mild to moderate in severity, and the majority had resolved or were resolving at the end of the study period. Conclusion: In clinical practice, PF tafluprost/timolol FC provided statistically and clinically significant IOP reductions in patients with OAG and OHT insufficiently controlled on or intolerant to PGA or beta-receptor blocker monotherapy. The full IOP reduction appeared at week 4 and was maintained over the 6-month study period. Key symptoms of ocular surface health improved. Trial Registration: European Union electronic Register of Post-Authorisation Studies (EU PAS) register number, EUPAS22204.publishersversionPeer reviewe