Elevated Levels of Plasma IgA Autoantibodies against Oxidized LDL Found in Proliferative Diabetic Retinopathy but Not in Nonproliferative Retinopathy

Aims. This study investigated the association of autoantibodies binding to oxidized low-density lipoproteins (oxLDL) in diabetic retinopathy (DR). Methods. Plasma from 229 types 1 and 2 patients with DR including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) was analysed with ELISA-based assay to determine IgA, IgG, and IgM autoantibody levels binding to oxLDL. The controls were 106 diabetic patients without retinopathy (NoDR) and 139 nondiabetic controls (C). Results. PDR group had significantly higher IgA autoantibody levels than DME or NoDR: mean 94.9 (SD 54.7) for PDR, 75.5 (41.8) for DME ( = 0.001), and 76.1 (48.2) for NoDR ( = 0.008). There were no differences in IgG, IgM, or IgA that would be specific for DR or for DME. Type 2 diabetic patients had higher levels of IgA autoantibodies than type 1 diabetic patients (86.0 and 65.5, resp., = 0.004) and the highest levels in IgA were found in type 2 diabetic patients with PDR (119.1, > 0.001). Conclusions. IgA autoantibodies were increased in PDR, especially in type 2 diabetes. The high levels of IgA in PDR, and especially in type 2 PDR patients, reflect the inflammatory process and enlighten the role of oxLDL and its autoantibodies in PDR

Elevated Levels of Plasma IgA Autoantibodies against Oxidized LDL Found in Proliferative Diabetic Retinopathy but Not in Nonproliferative Retinopathy

Peer reviewe

Characterization of metabolic interrelationships and in silico phenotyping of lipoprotein particles using self-organizing maps

Peer reviewe

Relief of asthenopic symptoms with orthoptic exercises in convergence insufficiency is achieved in both adults and children

Background: Asthenopic symptoms associated with convergence insufficiency (CI) may compromise a person's ability to work or study. We investigated the effectiveness of orthoptic exercises in relieving symptoms related to CI and long-time results in adults and children. Methods: The data were retrospectively gathered from the patient clinical files. A total of 135 patients met the inclusion criteria of suffering asthenopic symptoms and CI but had not received prior strabismus surgery or orthoptic exercises. Results: The mean age was 26 ± 17 years, 74% of them were female. The patients (N = 135) suffered from CI and had at least one of the following symptoms: eyestrain, blurring of vision, problems in reading and while doing work-up at close distance or headache. In the two-year follow-up time, 4% of the patients needed to be retreated and 3% of the patients required strabismus surgery. There were no significant differences between adults and children in near point of convergence (NPC), number of visits needed or fusional vergence at the end of treatment nor did the outcome depend on the number of visits. 59.5% of children vs. 51.9% of adults were free of symptoms when completing the exercises. Conclusions: In conclusion orthoptic exercises are effective in relieving asthenopic symptoms in adults and children. The effects of orthoptic exercises on NPC and fusional vergence were equal in adults and in children and not dependent on the number of visits needed for successful outcome. With orthoptic exercises it is possible to achieve longstanding relief on the symptoms of CI

Correlation of iCare ic100 tonometry with iCare TA01i in screening of unselected population in Northern Finland Birth Cohort Eye study

Abstract Purpose: iCare tonometers are easy-to-use and portable devices for measuring the intraocular pressure (IOP). Purpose was to evaluate the IOP values measured by both novel iCare ic100 and conventional model TA01i devices in unselected population. Methods: IOP was measured with iCare ic100 and TA01i tonometers in 149 participants aged 32–33 years (born in 1985 or 1986) of the Northern Finland Birth Cohort Eye 2 study. The right eye of each participant was selected for analysis. We also collected data on axial length, corneal curvature and central corneal thickness (CCT). Bland-Altman plot was used for comparing the values obtained by these devices. Results: Mean IOP measured with the ic100 device was 13.8 (3.4) mmHg, with TA01i it was 12.5 (3.0) mmHg. The mean difference between these devices was 1.30 mmHg (p < 0.001) and R² was 0.694. In Bland-Altman analysis, the agreement between the two tonometers ic100 and TA01i was constantly good (mean difference −1.30, ic100 device showing higher measures). There was a correlation between IOP and CCT (r = 0.269, p < 0.001 for ic100 and r  = 0.255, p  = 0.002 for TA01i), but not with IOP and corneal curvature or IOP and axial length. Conclusions: In summary, we found ic100 rebound tonometry to be both reliable and effective, although CCT may influence IOP measurements with ic100 and TA01i. Therefore, iCare ic100 is suitable for IOP measurement in large cohort studies

Reduced evoked activity and cortical oscillations are correlated with anisometric amblyopia and impairment of visual acuity

Amblyopia is a developmental disorder associated with abnormal visual experience during early childhood commonly arising from strabismus and/or anisometropia and leading to dysfunctions in visual cortex and to various visual deficits. The different forms of neuronal activity that are attenuated in amblyopia have been only partially characterized. In electrophysiological recordings of healthy human brain, the presentation of visual stimuli is associated with event-related activity and oscillatory responses. It has remained poorly understood whether these forms of activity are reduced in amblyopia and whether possible dysfunctions would arise from lower- or higher-order visual areas. We recorded neuronal activity with magnetoencephalography (MEG) from anisometropic amblyopic patients and control participants during two visual tasks presented separately for each eye and estimated neuronal activity from source-reconstructed MEG data. We investigated whether event-related and oscillatory responses would be reduced for amblyopia and localized their cortical sources. Oscillation amplitudes and evoked responses were reduced for stimuli presented to the amblyopic eye in higher-order visual areas and in parietal and prefrontal cortices. Importantly, the reduction of oscillation amplitudes but not that of evoked responses was correlated with decreased visual acuity in amblyopia. These results show that attenuated oscillatory responses are correlated with visual deficits in anisometric amblyopia.Peer reviewe

Relationship between retinal vessel diameter with both retinal nerve fibre layer thickness and optic nerve head parameters in middle‐aged Caucasians:the Northern Finland Birth Cohort Eye study

Abstract Purpose: To study the normal relationship between retinal vessel diameter (RVD) with retinal nerve fibre layer (RNFL) thickness and optic nerve head (ONH) parameters in a cohort of middle‐aged Caucasians. Methods: We investigated 3070 individuals (6140 eyes). Central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) were measured in the right eye using a semi‐automated computer‐assisted program. Retinal nerve fibre layer (RNFL) thickness and ONH parameters were assessed with Heidelberg retinal tomography (HRT). Results: Data from 2217 persons were analysed including RNFL, CRAE, CRVE, sex, body mass index, mean arterial pressure, diabetes status, smoking status, optic disc area, rim area, spherical refraction and intraocular pressure. A larger RVD was associated with a thicker mean global RNFL thickness especially in global and inferior segments of the retina and with larger optic discs. Each 10 μm increase in the retinal arteriolar calibre was associated with a 5.58 μm increase in mean global RNFL thickness; the corresponding value for a 10 μm increase in venular calibre was 3.79 μm (p < 0.001 for both). Retinal venular calibre displayed consistent associations with RNFL thickness in both genders (p < 0.001 for all), whereas the association of arteriolar calibre and RNFL was more prominent in men (p < 0.001). Conclusion: We found strong associations between larger RVD and thicker RNFL in all subjects. This study helps to clarify the association between RVD, RNFL thickness and ONH parameters and provides normal values for middle‐aged Caucasians that will help in future studies investigating the role of vascular aetiology in systemic and eye diseases

Combined structure–function analysis in glaucoma screening

Abstract Aim: To assess the applicability of a structure–function (S-F) analysis combining spectral-domain optical coherence tomography (SD-OCT) and standard automated perimetry (SAP) in glaucoma screening in a middle-aged population. Methods: A randomised sample of 3001 Caucasian participants aged 45–49 years of the Northern Finland Birth Cohort Eye Study was examined. We performed an eye examination, including 24–2 SAP, optic nerve head (ONH) and retinal nerve fibre layer (RNFL) photography and SD-OCT of the peripapillary RNFL. The S-F report was generated by Forum Glaucoma Workplace software. OCT, SAP and the S-F analysis were evaluated against clinical glaucoma diagnosis, that is, the positive ‘2 out of 3’ rule based on the clinician’s evaluation of ONH and RNFL photographs and visual fields (VFs). Results: At a specificity of 97.5%, the sensitivity for glaucomatous damage was 26% for abnormal OCT, 35% for SAP and 44% for S-F analysis. Estimated areas under the curve were 0.74, 0.85 and 0.76, and the corresponding positive predictive values were 8 %, 10% and 12%, respectively. By applying a classification tree approach combining OCT, SAP and defect localisation data, a sensitivity of 77% was achieved at 90% specificity. In a localisation analysis of glaucomatous structural and functional defects, the correlation with glaucoma increased significantly if the abnormal VF test points were located on borderline or abnormal OCT zones. Conclusions: SAP performs slightly better than OCT in glaucoma screening of middle-aged population. However, the diagnostic capability can be improved by S-F analysis

Novel variants and phenotypes widen the phenotypic spectrum of GABRG2-related disorders

Abstract Purpose: Next-generation sequencing (NGS) has made genetic testing of patients with epileptic encephalopathies easier — novel variants are discovered and new phenotypes described. Variants in the same gene — even the same variant — can cause different types of epilepsy and neurodevelopmental disorders. Our aim was to identify the genetic causes of epileptic encephalopathies in paediatric patients with complex phenotypes. Methods: NGS was carried out for three patients with epileptic encephalopathies. Detailed clinical features, brain magnetic resonance imaging and electroencephalography were analysed. We searched the Human Gene Mutation Database for the published GABRG2 variants with clinical description of patients and composed a summary of the variants and their phenotypic features. Results: We identified two novel de novo GABRG2 variants, p.P282T and p.S306F, with new phenotypes including neuroradiological evidence of neurodegeneration and epilepsy of infancy with migrating focal seizures (EIMFS). One patient carried previously reported p.P83S variant with autism spectrum disorder (ASD) phenotype that has not yet been described related to GABRG2 disorders and a more severe epilepsy phenotype than reported earlier. In all, the literature search yielded twenty-two articles describing 27 different variants that were divided into two categories: those with self-limiting epilepsies and febrile seizures and those with more severe drug-resistant epileptic encephalopathies. Conclusion: This study further expands the genotypic and phenotypic spectrum of epilepsies associated with GABRG2 variants. More knowledge is still needed about the influence of the environment, genetic background and other epilepsy susceptibility genes on the phenotype of the specific GABRG2 variants