Blind spot and visual field anisotropy detection with flicker pupil perimetry across brightness and task variations

The pupil can be used as an objective measure for testing sensitivities across the visual field (pupil perimetry; PP). The recently developed gaze-contingent flicker PP (gcFPP) is a promising novel form of PP, with improved sensitivity due to retinotopically stable and repeated flickering stimulations, in a short time span. As a diagnostic tool gcFPP has not yet been benchmarked in healthy individuals. The main aims of the current study were to investigate whether gcFPP has the sensitivity to detect the blind spot, and upper versus lower visual field differences that were found before in previous studies. An additional aim was to test for the effects of attentional requirements and background luminance. A total of thirty individuals were tested with gcFPP across two separate experiments. The results showed that pupil oscillation amplitudes were smaller for stimuli presented inside as compared to outside the blind spot. Amplitudes also decreased as a function of eccentricity (i.e., distance to fixation) and were larger for upper as compared to lower visual fields. We measured the strongest and most sensitive pupil responses to stimuli presented on dark- and mid-gray backgrounds, and when observers covertly focused their attention to the flickering stimulus. GcFPP thus evokes pupil responses that are sensitive enough to detect local, and global differences in pupil sensitivity. The findings further encourage (1) the use of a gray background to prevent straylight without affecting gcFPPs sensitivity and (2) the use of an attention task to enhance pupil sensitivity

Impact of Bevacizumab on Visual Function, Tumor Size, and Toxicity in Pediatric Progressive Optic Pathway Glioma: A Retrospective Nationwide Multicentre Study

Backgrounds: Bevacizumab (BVZ) is used as a subsequent line of treatment for pediatric optic pathway glioma (OPG) in the case of progression. Data on the treatment effect concerning tumor progression and visual function are scarce and nationwide studies are lacking. Methods: We performed a retrospective, nationwide, multicentre cohort study including all pediatric patients with OPG treated with BVZ in the Netherlands (2009–2021). Progression-free survival, change in visual acuity and visual field, MRI-based radiologic response, and toxicity were evaluated. Results: In total, 33 pediatric patients with OPG were treated with BVZ (median 12 months). Visual acuity improved in 20.5%, remained stable in 74.4%, and decreased in 5.1% of 39 of all analysed eyes. The monocular visual field improved in 73.1%, remained stable in 15.4%, and decreased in 7.7% of 25 analysed eyes. Radiologic response at the end of therapy showed a partial response in 7 patients (21.9%), minor response in 7 (21.9%), stable disease in 15 (46.9%), and progressive disease in 3 (9.3%). Progression-free survival at 18 and 36 months after the start of BVZ reduced from 70.9% to 38.0%. Toxicity (≥grade 3 CTCAE) during treatment was observed in five patients (15.2%). Conclusion: Treatment of BVZ in pediatric patients with OPG revealed stabilisation in the majority of patients, but was followed by progression at a later time point in more than 60% of patients. This profile seems relatively acceptable given the benefits of visual field improvement in more than 70% of analysed eyes and visual acuity improvement in more than 20% of eyes at the cessation of BVZ

Blind spot and visual field anisotropy detection with flicker pupil perimetry across brightness and task variations

The pupil can be used as an objective measure for testing sensitivities across the visual field (pupil perimetry; PP). The recently developed gaze-contingent flicker PP (gcFPP) is a promising novel form of PP, with improved sensitivity due to retinotopically stable and repeated flickering stimulations, in a short time span. As a diagnostic tool gcFPP has not yet been benchmarked in healthy individuals. The main aims of the current study were to investigate whether gcFPP has the sensitivity to detect the blind spot, and upper versus lower visual field differences that were found before in previous studies. An additional aim was to test for the effects of attentional requirements and background luminance. A total of thirty individuals were tested with gcFPP across two separate experiments. The results showed that pupil oscillation amplitudes were smaller for stimuli presented inside as compared to outside the blind spot. Amplitudes also decreased as a function of eccentricity (i.e., distance to fixation) and were larger for upper as compared to lower visual fields. We measured the strongest and most sensitive pupil responses to stimuli presented on dark- and mid-gray backgrounds, and when observers covertly focused their attention to the flickering stimulus. GcFPP thus evokes pupil responses that are sensitive enough to detect local, and global differences in pupil sensitivity. The findings further encourage (1) the use of a gray background to prevent straylight without affecting gcFPPs sensitivity and (2) the use of an attention task to enhance pupil sensitivity

Gaze-Contingent Flicker Pupil Perimetry Detects Scotomas in Patients With Cerebral Visual Impairments or Glaucoma

The pupillary light reflex is weaker for stimuli presented inside as compared to outside absolute scotomas. Pupillograph perimetry could thus be an objective measure of impaired visual processing. However, the diagnostic accuracy in detecting scotomas has remained unclear. We quantitatively investigated the accuracy of a novel form of pupil perimetry. Methods: The new perimetry method, termed gaze-contingent flicker pupil perimetry, consists of the repetitive on, and off flickering of a bright disk (2 hz; 320 cd/m2; 4° diameter) on a gray background (160 cd/m2) for 4 seconds per stimulus location. The disk evokes continuous pupil oscillations at the same rate as its flicker frequency, and the oscillatory power of the pupil reflects visual sensitivity. We monocularly presented the disk at a total of 80 locations in the central visual field (max. 15°). The location of the flickering disk moved along with gaze to reduce confounds of eye movements (gaze-contingent paradigm). The test lasted ~5 min per eye and was performed on 7 patients with cerebral visual impairment (CVI), 8 patients with primary open angle glaucoma (age >45), and 14 healthy, age/gender-matched controls. Results: For all patients, pupil oscillation power (FFT based response amplitude to flicker) was significantly weaker when the flickering disk was presented in the impaired as compared to the intact visual field (CVI: 12%, AUC = 0.73; glaucoma: 9%, AUC = 0.63). Differences in power values between impaired and intact visual fields of patients were larger than differences in power values at corresponding locations in the visual fields of the healthy control group (CVI: AUC = 0.95; glaucoma: AUC = 0.87). Pupil sensitivity maps highlighted large field scotomas and indicated the type of visual field defect (VFD) as initially diagnosed with standard automated perimetry (SAP) fairly accurately in CVI patients but less accurately in glaucoma patients. Conclusions: We provide the first quantitative and objective evidence of flicker pupil perimetry's potential in detecting CVI-and glaucoma-induced VFDs. Gaze-contingent flicker pupil perimetry is a useful form of objective perimetry and results suggest it can be used to assess large VFDs with young CVI patients whom are unable to perform SAP

Impact of systemic anticancer therapy in pediatric optic pathway glioma on visual function: A systematic review

Pediatric optic pathway glioma (OPG) can seriously decrease visual function in the case of progression. Systemic anticancer therapy (SAT) is considered the treatment of first choice for unresectable OPG. New SAT modalities for the treatment of progressive OPG have been introduced in the last decade, including VEGF and MAPK pathway inhibition. This systematic review evaluated the effect of SAT on change in visual acuity and visual field in OPG. A systematic review was performed on SAT for OPG (January 1990 to August 2020). MEDLINE and EMBASE (Ovid) were searched for studies reporting on change in visual acuity and visual field after treatment with SAT for OPG. Overall, 11 series, including 358 patients, fulfilled the eligibility criteria. After follow-up of median 3.7 years (range: cessation of SAT- 8.2 years), improvement in binocular VA was found in 0-45% of studies, stability in 18-77% and a decrease in 0-82%. Two studies reported on change in visual field (improvement in 19% and 71% of patients), although either the change was not defined or the testing strategy was lacking. Considerable heterogeneity was present among the included studies, such as variety in the combinations of SAT administered, status of neurofibromatosis type 1, definition regarding change in visual acuity, 1- or 2-eye analysis, diversity in anatomic location, and extent of follow-up, all of which made meta-analysis inappropriate. This systematic review suggests that the impact of SAT in OPG on visual function is still unclear. The wide ranges reported on the efficacy of SAT and the observed heterogeneity highlight the need for prospective studies with uniform definitions of outcome parameters

Large variability in recommendations for return to daily life activities after knee arthroplasty among Dutch hospitals and clinics: a cross-sectional study.

BACKGROUND AND PURPOSE: Recommendations concerning the return to daily life activities, including work and sport, after knee arthroplasty (KA) are essential for setting realistic patient expectations. Fulfillment of these expectations contributes to more satisfaction and enhanced recovery after KA. However, scientific evidence for such recommendations is limited, and recommendations are often based only on healthcare professionals' expert opinions. We summarized the current recommendations regarding return to daily life activities provided by Dutch hospitals and clinics to KA patients. MATERIAL AND METHODS: Recommendations of 43 Dutch hospitals and clinics were identified, representing the advice provided to 70% of the total Dutch KA patients. Recommendations were retrieved from content from websites (n = 8), brochures (n = 40), and mobile phone applications (n = 9). RESULTS: Recommendations for 24 daily life activities were identified. Individual hospitals and clinics provided recommendations for, on average, 9 (0-15) of these activities. Recommendations varied greatly. For example, recommendations regarding when to resume cycling after KA were provided by 36 of the 43 hospitals and clinics and varied from 3 weeks to 3 months. INTERPRETATION: Recommendations for return to daily life activities are often missing and vary considerably between Dutch hospitals and clinics. These findings show the need for more uniformity across healthcare providers regarding recommendations for postoperative return to daily life activities

A novel mutation of laminin beta 2 (LAMB2) in two siblings with renal failure

This report describes a novel mutation of LAMB2, the gene associated with Pierson syndrome (microcoria-congenital nephrosis syndrome), in two female siblings. The c.970T > C p.(Cys324Arg) mutation in the LAMB2 gene affects one of the eight highly conserved cysteine residues within the first EGF-like module of the laminin beta 2 protein. These residues form disulfide bonds in order to achieve a correct 3D structure of the protein. The reported phenotype is considered a relatively mild variant of Pierson syndrome and is associated with later-onset (18 months) therapy-resistant nephrotic syndrome leading to renal failure, and ocular abnormalities consisting of high myopia, microcoria, diverse retinal abnormalities, hence a low level of visual acuity. Importantly, the reported LAMB2 mutation was associated with normal neurological development in both siblings. Conclusion : this report presents the variability of the renal, ocular and neurological phenotypes associated with LAMB2 mutations and underscores the importance of ophthalmologic examination in all children with unexplained renal insufficiency or nephrotic syndrom

Platelets bridging the gap between gut dysbiosis and neuroinflammation in stress-linked disorders: A narrative review.

In this narrative review, we examine the association between gut dysbiosis, neuroinflammation, and stress-linked disorders, including depression, anxiety, and post-traumatic stress disorder (PTSD), and investigate whether tryptophan (TRP) metabolism and platelets play a role in this association. The mechanisms underlying the aetiology of stress-linked disorders are complex and not yet completely understood. However, a potential link between chronic inflammation and these disorders may potentially be found in TRP metabolism and platelets. By critically analysing existing literature on platelets, the gut microbiome, and stress-linked disorders, we hope to elicit the role of platelets in mediating the effects on serotonin (5-HT) levels and neuroinflammation. We have included studies specifically investigating platelets and TRP metabolism in relation to inflammation, neuroinflammation and neuropsychiatric disorders. Alteration in microbial composition due to stress could contribute to increased intestinal permeability, facilitating the translocation of microbial products, and triggering the release of pro-inflammatory cytokines. This causes platelets to become hyperactive and secrete 5-HT into the plasma. Increased levels of pro-inflammatory cytokines may also lead to increased permeability of the blood-brain barrier (BBB), allowing inflammatory mediators entry into the brain, affecting the balance of TRP metabolism products, such as 5-HT, kynurenic acid (KYNA), and quinolinic acid (QUIN). These alterations may contribute to neuroinflammation and possible neurological damage. Furthermore, platelets can cross the compromised BBB and interact with astrocytes and neurons, leading to the secretion of 5-HT and pro-inflammatory factors, exacerbating inflammatory conditions in the brain. The mechanisms underlying neuroinflammation resulting from peripheral inflammation are still unclear, but the connection between the brain and gut through the bloodstream could be significant. Identifying peripheral biomarkers and mechanisms in the plasma that reflect neuroinflammation may be important. This review serves as a foundation for further research on the association between the gut microbiome, blood microbiome, and neuropsychiatric disorders. The integration of these findings with protein and metabolite markers in the blood may expand our understanding of the subject. [Abstract copyright: Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.

Blind spot and visual field anisotropy detection with flicker pupil perimetry across brightness and task variations

The pupil can be used as an objective measure for testing sensitivities across the visual field (pupil perimetry; PP). The recently developed gaze-contingent flicker PP (gcFPP) is a promising novel form of PP, with improved sensitivity due to retinotopically stable and repeated flickering stimulations, in a short time span. As a diagnostic tool gcFPP has not yet been benchmarked in healthy individuals. The main aims of the current study were to investigate whether gcFPP has the sensitivity to detect the blind spot, and upper versus lower visual field differences that were found before in previous studies. An additional aim was to test for the effects of attentional requirements and background luminance. A total of thirty individuals were tested with gcFPP across two separate experiments. The results showed that pupil oscillation amplitudes were smaller for stimuli presented inside as compared to outside the blind spot. Amplitudes also decreased as a function of eccentricity (i.e., distance to fixation) and were larger for upper as compared to lower visual fields. We measured the strongest and most sensitive pupil responses to stimuli presented on dark- and mid-gray backgrounds, and when observers covertly focused their attention to the flickering stimulus. GcFPP thus evokes pupil responses that are sensitive enough to detect local, and global differences in pupil sensitivity. The findings further encourage (1) the use of a gray background to prevent straylight without affecting gcFPPs sensitivity and (2) the use of an attention task to enhance pupil sensitivity

Diagnostic accuracy of retinal optical coherence tomography in children with a newly diagnosed brain tumour

Purpose: To estimate the diagnostic accuracy of circumpapillary retinal nerve fibre layer (RNFL) thickness and macular ganglion cell layer–inner plexiform layer (GCL-IPL) thickness measurements to discriminate an abnormal visual function (i.e. abnormal age-based visual acuity and/or visual field defect) in children with a newly diagnosed brain tumour. Methods: This cross-sectional analysis of a prospective longitudinal nationwide cohort study was conducted at four hospitals in the Netherlands, including the national referral centre for paediatric oncology. Patients aged 0–18 years with a newly diagnosed brain tumour and reliable visual acuity and/or visual field examination and optical coherence tomography were included. Diagnostic accuracy was evaluated with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results: Of 115 patients included in the study (67 [58.3%] male; median age 10.6 years [range, 0.2–17.8 years]), reliable RNFL thickness and GCL-IPL thickness measurements were available in 92 patients (80.0%) and 84 patients (73.0%), respectively. The sensitivity for detecting an abnormal visual function was 74.5% for average RNFL thickness and 41.7% for average GCL-IPL thickness at a specificity of 44.5% and 82.9%, respectively. The PPV and NPV were 33.0% and 82.6% for the average RNFL thickness and 57.1% and 82.2% for the average GCL-IPL thickness. Conclusion: An abnormal visual function was discriminated correctly by using the average RNFL thickness in seven out of ten patients and by using the average GCL-IPL thickness in four out of ten patients. The relatively high NPVs signified that patients with normal average RNFL thickness and average GCL-IPL thickness measurements had a relative high certainty of a normal visual function