Nomdo M. Jansonius

Purpose: To investigate structural changes in the retina and optic nerve head (ONH) of children with cerebral visual impairment (CVI) across different timing of damage (TOD), and to relate these structural changes to visual field (VF) loss severity and pattern. Methods: Ninety‐five children with CVI and 47 age‐matched controls underwent optical coherence tomography (OCT) and static VF testing. TOD was categorized as prenatal, preterm, perinatal, postnatal, genetic or combined. Four OCT parameters were analysed (peripapillary retinal nerve fibre layer [pRNFL] thickness, ganglion cell inner plexiform layer [GCIPL] thickness, optic disc area (DA), cup‐to‐disc ratio [CDR]); for VF, we used mean defect (MD) and VF loss pattern. Generalized linear mixed‐effects models were used to compare the OCT parameters between TOD categories and controls. The relationship between OCT parameters and MD was assessed with Spearman correlation. Results: pRNFL and GCIPL thickness were significantly reduced for the preterm ( p < 0.001), perinatal ( p = 0.003), postnatal ( p = 0.001) and genetic ( p < 0.001) categories. DA was smaller for the genetic category ( p = 0.014), and CDR was larger for the preterm ( p = 0.03), perinatal ( p = 0.03) and postnatal ( p = 0.02) categories. MD was associated with pRNFL ( ρ = −0.35, p = 0.001) and GCIPL thickness ( ρ = −0.28, p = 0.01); especially in cases with profound VF loss, the VF loss pattern agreed well with that of GCIPL thinning. Conclusion: CVI is associated with structural changes in the inner retinal layers and ONH, in a TOD‐specific manner. Structural changes relate to MD and VF loss patterns.

Early detection of glaucoma prevents blindness but its low population-based prevalence impedes cost-effective screening. We investigated whether genetic pre-screening could increase the prior probability. Design, methods, and primary analysis were pre-specified and published previously. In this prospective study, we invited 1829 participants aged 55 + from the Dutch Lifelines cohort, selecting from either the highest or lowest 20% of a GWAS-based genetic risk score distribution; subgroups had similar age and gender. Researchers were blinded to subgroup allocation; participants to genetic risk selection. Participants underwent perimetry, optical coherence tomography, fundus photography, tonometry, pachymetry, and visual acuity assessment. Abnormalities prompted a full ophthalmic examination. Participants were classified as definite, probable, or possible open-angle glaucoma, or as unaffected. We calculated the relative risk of combined definite and probable glaucoma for high versus low genetic risk, adjusting for age, sex, and genotyping platform. 1022 participants (median [interquartile range] age 64 [59–70] years, 53% female, Northwestern European ancestry) agreed to participate and were included, 487 with high and 535 with low genetic risk. Of these, 59 (age 70 [64–76] years) were classified as definite (29 with high and 2 with low genetic risk) or probable (21 and 7) glaucoma. Relative risk was 7.4 (95% confidence interval 3.7–14.7), indicating that participants with high genetic risk were over seven times more likely to be classified with glaucoma than those with low risk. Stratifying the general population based on genetic risk strongly increases the prior probability of glaucoma and may enable a cost-effective screening approach.

Background: Individuals with an abnormal birth are at risk of having ophthalmic complications and visual impairment. The aim of this study was to understand the relationship between birth-related characteristics and vision-related quality of life (VR-QoL) in adults in the general population. Methods: We used data from Lifelines, a population-based cohort study from the North of Netherlands (n = 167,000). We included individuals with National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25) data (n = 29,840; 18–55 years). Included birth-related characteristics were gestation length, birth weight, mode of delivery, and the presence of birth defects. We used ordinal regression with the NEI-VFQ-25 items as dependent variable and the birth-related characteristics as independent variables. Analyses were adjusted for age and gender, and corrected for multiple hypothesis testing using false discovery rate (FDR). Results: Participants with birth defects directly related to eye or brain development showed a poor VR-QoL in 9/10 subscales (FDR-corrected P value q < 0.001 to 0.05) with the most pronounced effect for difficulties performing peripheral vision-related activities. Individuals with birth defects not directly related to eye or brain development showed a poor VR-QoL in 4/10 subscales (q = 0.02 to 0.05). Early preterm birth was related to the general vision (q = 0.02) and vision specific social functioning (q = 0.05) subscales. High birth weight (>4500 g) contributed to general vision problems (q = 0.05), and vacuum or forceps mode of delivery was associated with difficulties performing activities under low luminance conditions (q = 0.02). Conclusion: At the level of the general population, birth-related characteristics are related to VR-QoL. To elucidate the underlying mechanisms, future studies could add visual function to the questionnaire outcomes.

Binocular visual field (VF) loss affects vision-related quality of life (VR-QoL) but the relationship between specific VF loss patterns and difficulties with specific tasks remains poorly understood. Archetypal analysis offers a promising method to elucidate spatial patterns of VF loss. In this study, we aimed to develop archetypes for binocular VF loss and assess their relationship with VR-QoL. We included 7305 pairs of reliable standard automated perimetry (24-2 SITA fast and standard) test results of patients from 5 glaucoma clinics in England from a Healthcare Quality Improvement Partnership-funded audit. We executed an archetypal analysis on the corresponding integrated VFs (estimates of the binocular VFs from pairs of monocular VFs) to identify the best-fitting set of archetypes from our dataset. Then, we used these archetypes to deconstruct the binocular VF of 269 patients with glaucoma from the Netherlands that had completed 4 different VR-QoL questionnaires. Finally, relationships between each of the archetypes and different aspects of VR-QoL were analyzed. The archetypal analysis demonstrated that a solution comprising 12 archetypes provides the best-fitting model. Our analysis of the 269 patients' with glaucoma data showed various significant and plausible relationships between the different archetypes and various aspects of VR-QoL. Our results demonstrate how archetypes can elucidate relationships between the location of a VF defect and different aspects of VR-QoL in glaucoma. This may help clinicians and patients better understand the impact of different types of VF defects.

Purpose: Acquired brain injury (ABI) may cause homonymous visual field (VF) defects. Standard automated perimetry (SAP) is the gold standard for VF assessment, but it can be challenging in ABI. Continuous visual stimulus tracking (SONDA; Standardised Oculomotor and Neurological Disorders Assessment) simplifies the perimetric task to following a moving stimulus on a screen. We investigated whether tracking performance (agreement between gaze and stimulus position) measured with a SONDA‐based eye movement perimetry technique (SONDA‐EMP) (1) can detect visual function loss in patients with homonymous VF defects, (2) can quantify visual function loss (in terms of SAP Mean Sensitivity [MS]) and (3) shows a learning effect. Methods: Tracking performance was evaluated in 16 cases with unilateral ABI (median [IQR] age 66 [62–68] years; SAP MS 19 [15–21] dB; 8/8 with left‐/right‐sided VF defect) and compared to previously collected data of 36 controls (age 70 [67–72] years). All participants monocularly tracked a moving stimulus (Goldmann size III) at three Weber contrasts (40%, 160% and 640%), while their eye movements were recorded. Results: ABI significantly decreased tracking performance ( p < 0.0001) compared to controls at all contrasts, independently of VF defect side ( p = 0.53). Performance improved from 40% to 160% contrast ( p < 0.0001), but not from 160% to 640% ( p = 0.53). SAP MS correlated moderately to strongly with tracking performance ( r = 0.46 [ p = 0.07], 0.73 [ p = 0.01], 0.67 [ p = 0.004], for 40%, 160% and 640% contrast, respectively). Retesting showed no significant learning effect. Conclusion: SONDA‐EMP can detect visual function loss from ABI. The reduction in tracking performance depends on the amount of VF loss.

Purpose: Standard automated perimetry (SAP) is the gold standard for functional assessment in glaucoma. SAP can be too demanding for some groups of patients. Continuous visual stimulus tracking (SONDA: Standardized Oculomotor and Neurological Disorders Assessment) simplifies the perimetric task to following a moving stimulus on a screen. In this study we evaluated the screening performance of SONDA-based eye movement perimetry (SONDA-EMP) in glaucoma. To explore generalizability, we evaluated an experimental setup (SONDA-Eyelink) and a clinic-ready version (SONDA-Neon). Methods: SONDA-Eyelink and SONDA-Neon measurements were performed in 100 cases with glaucoma (36, 36, and 28 with early, moderate, and severe glaucoma, respectively) and 100 age-similar controls. Participants monocularly tracked a moving stimulus (Goldmann size III) at 40% contrast (both setups) and 160% (SONDA-Eyelink). Eye movements were continuously recorded. Outcome was the agreement between gaze and stimulus position. We used previously collected glaucoma case-control data to build a continuous ‘glaucoma screening score’. This score was used for an ROC-analysis applied to the current, independently collected dataset. We predefined good screening performance as: at 95% specificity, a sensitivity of at least 50%, 90%, and 100% for early, moderate, and severe glaucoma, respectively. Results: At 95% specificity, the sensitivity of SONDA-Eyelink was 58, 94, and 100% at 40% contrast and 56, 97, and 100% at 160% contrast for early, moderate, and severe glaucoma, respectively. Sensitivity was 53, 94, and 100% for SONDA-Neon. Conclusions: SONDA-EMP is a novel, fast, and intuitive method to screen for visual function loss in glaucoma.

Continuous visual stimulus tracking could be used as an easy alternative to standard automated perimetry (SAP) for visual function screening. With continuous visual stimulus tracking, we simplified the perimetric task to following a moving dot on a screen with the eyes. Here, we determined whether tracking performance (the agreement between gaze and stimulus position) enables the detection and quantification of glaucomatous visual function loss (in terms of SAP), and whether it shows a learning effect. We evaluated the tracking performance of 36 cases with early, moderate, or severe glaucoma (median with interquartile range [IQR] age = 70 [67-74] years) and 36 controls (median = 70, IQR = 67-72 years). All participants monocularly tracked a moving stimulus (Goldmann size III) at 3 Weber contrast levels: 40, 160, and 640%, while their eye movements were recorded. Glaucoma decreased the tracking performance, with the most severe reduction in the severe glaucoma cases. A distinction between groups was possible, but depended on the contrast level: tracking performance of early glaucoma cases was significantly different from controls only at 40% contrast. Within the cases, glaucomatous visual function loss (SAP Mean Sensitivity [MS]) was best correlated with tracking performance when using 160% contrast. There was no significant learning effect. Overall, the data indicate that it is possible to detect and quantify glaucomatous visual function loss with continuous visual stimulus tracking. Continuous visual stimulus tracking is an easy, fast, and intuitive technique that has the potential for diagnostic applications in detection of new glaucoma cases and monitoring of previously diagnosed cases.

PURPOSE: Primary open angle glaucoma (POAG, hereafter referred to as glaucoma) is a neuro-ophthalmic disease characterized by progressive degeneration of the retinal ganglion cells and nerve fibers. However, the exact pathogenesis of this disease remains unresolved, notably including its effect on the neural circuits of the visual pathway and cortex. METHODS: We used both resting state (RS) and stimulus-driven functional MRI and applied a novel analysis technique (Bayesian Connective Field Modelling) to investigate the intra-cortical functional connective organization of the early visual cortex of patients with POAG. Analogous to population receptive field modelling for stimulus-driven activity, our connective field approach models how the activity in one cortical area (e.g. V2) can be explained based on that of another (e.g. V1). RESULTS: We compared the CF parameters obtained for the early visual cortical areas in glaucoma to those of control participants. Our results show that in both RS and stimulus-driven conditions, CF sizes in early visual areas are smaller in glaucoma compared to control participants. To assess if these differences could be related to the ocular damage altering the visual input to the visual cortex, the control participants also observed the visual stimuli with a simulated scotoma (SS), designed to match the visual sensitivity of a participant affected by glaucoma as assessed using standard automated perimetry (SAP). In this condition, no differences in CF size were observed. Moreover, we found that CF size did not correlate with glaucoma severity, as assessed using both SAP and optical coherence tomography (OCT). CONCLUSION: The observed differences in CF metrics may be the result of local reorganization or neurodegeneration of the early visual cortex that must have developed already at an early disease stage.

Purpose: The 6-item Vision-related Quality of life and Limitations questionnaire (VQL-6) is a screening instrument that signals a need for additional low vision care in patients with chronic ophthalmic diseases. This study aims to (1) determine the optimal scoring method for the VQL-6 and (2) evaluate its discriminative capacity for clinical use. Methods: Patients with glaucoma and retina- and cornea-related disorders completed the VQL-6 and participated in an interview designed to distinguish between patients with and without a need of additional care. For the two subscales (general health and quality of life, HQOL, and vision-related limitations, VL) we compared a scoring model with equal item weights to a cross-validated model using regression weights. The optimal scoring method and discriminative capacity of the subscales were determined using receiver operating characteristics (ROC) analysis, with the interview outcome as gold standard. Sensitivities were evaluated at specificities of 90 and 95%. Results: In 297 interview assessments, 96 patients (32%) appeared to need additional care. Both scoring models demonstrated very similar area under the ROC curves (AUC). The selected equal weight model yielded an AUC of 0.91 (95% confidence interval 0.87-0.94) for VL and 0.71 (0.65-0.77) for HQOL. For VL, sensitivity was 72 and 64% at 90 and 95% specificity, respectively. Corresponding HQOL sensitivities were 34 and 17%. Conclusions: The subscale VL shows excellent discriminative capacity and outperformed HQOL. Future studies should explore the feasibility of the VQL-6 in clinical practice.