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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. 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). 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). 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.

Myopic eyes have an increased risk of glaucoma. However, glaucomatous changes in a myopic eye are often difficult to detect. Classic structural and functional investigations to diagnose glaucoma may be confounded by myopia. Here, we identify some of the common pitfalls in interpreting these structural parameters, and the possible solutions that could be taken to overcome them. For instance, in myopic eyes, we discuss the limitations and potential sources of error when using neuroretinal rim parameters, and retinal nerve fibre layer and ganglion cell-inner plexiform layer thickness measurements. In addition, we also review new developments and potential adjuncts in structural imaging such as the assessment of the retinal nerve fibre layer texture, and the examination of the microcirculation of the optic nerve head using optical coherence tomography angiography. For the functional assessment of glaucoma, we discuss perimetric strategies that may aid in detecting characteristic visual field defects in myopic glaucoma. Ultimately, the evaluation of glaucoma in myopia requires a multimodal approach, to allow correlation between structural and functional assessments. This review provides overview on how to navigate this diagnostic dilemma.

The alternative mechanical theory of glaucoma, in which an increased pressure difference across the lamina cribrosa (difference between intraocular and intracranial pressure; IOP and ICP), rather than solely an elevated IOP, leads to structural and functional vision loss, is still controversial. If the theory is true, a drug that simultaneously lowers both the IOP and ICP may be ineffective. The aim of this study was to determine how acetazolamide (AAZ; a drug prescribed in glaucoma that aims to lower the IOP) affects both IOP and ICP in glaucoma patients and to compare the magnitude and time course of the induced pressure changes with those of healthy subjects not taking AAZ. IOP and noninvasive ICP (measured through emissions from the ear) were measured in 20 glaucoma patients taking 125 mg of AAZ twice daily. Measurements were taken for 30 minutes before taking the drug and for 2 hours post-ingestion. Comparisons were made with 13 age-similar controls. After 12 hours with no anti-glaucoma medication, AAZ did not further reduce IOP in glaucoma patients compared to controls (P = 0.58) but did reduce ICP compared to controls (P = 0.035), by approximately 4 mmHg. Our findings suggest that there are periods during the day when the pressure difference across the lamina cribrosa is larger in case of AAZ use. Future studies should focus on improving the noninvasive ICP testing, different doses and dosing schedules of AAZ, and the time course of IOP in glaucoma patients not taking AAZ.

Background To investigate whether copy number variations (CNVs) are implicated in molecular mechanisms underlying primary open-angle glaucoma (POAG), we used genotype data of POAG individuals and healthy controls from two case-control studies, AGS ( n  = 278) and GLGS-UGLI ( n  = 1292). PennCNV, QuantiSNP, and cnvPartition programs were used to detect CNV. Stringent quality controls at both sample and marker levels were applied. The identified CNVs were intersected in CNV region (CNVR). After, we performed burden analysis, CNV-genome-wide association analysis, gene set overrepresentation and pathway analysis. In addition, in human eye tissues we assessed the expression of the genes lying within significant CNVRs. Results We reported a statistically significant greater burden of CNVs in POAG cases compared to controls ( p -value = 0,007). In common between the two cohorts, CNV-association analysis identified statistically significant CNVRs associated with POAG that span 11 genes ( APC , BRCA2, COL3A1, HLA-DRB1, HLA-DRB5, HLA-DRB6, MFSD8 , NIPBL, SCN1A, SDHB , and ZDHHC11 ). Functional annotation and pathway analysis suggested the involvement of cadherin, Wnt signalling, and p53 pathways. Conclusions Our data suggest that CNVs may have a role in the susceptibility of POAG and they can reveal more information on the mechanism behind this disease. Additional genetic and functional studies are warranted to ascertain the contribution of CNVs in POAG.

Background: Primary open-angle glaucoma (POAG) patients exhibit widespread white matter (WM) degeneration throughout their visual pathways. Whether this degeneration starts at the pre- or post-geniculate pathways remains unclear. In this longitudinal study, we assess the progression of WM degeneration exhibited by the pre-geniculate optic tracts (OTs) and the post-geniculate optic radiations (ORs) of POAG patients over time, aiming to determine the source and pattern of spread of this degeneration. Methods: Diffusion-weighted MRI scans were acquired for 12 POAG patients and 14 controls at two time-points 5.4 ± 2.1 years apart. Fiber density (FD), an estimate of WM axonal density, was computed for the OTs and ORs of all participants in an unbiased longitudinal population template space. First, FD was compared between POAG patients and the controls at time-point 1 (TP1) and time-point 2 (TP2) independently. Secondly, repeated measures analysis was performed for FD change in POAG patients between the two time-points. Finally, we compared the rate of FD change over time between the two groups. Results: Compared to the controls, POAG patients exhibited significantly lower FD in the left OT at TP1 and in both OTs and the left OR at TP2. POAG patients showed a significant loss of FD between the time-points in the right OT and both ORs, while the left OR showed a significantly higher rate of FD loss in POAG patients compared to the controls. Conclusions: We find longitudinal progression of neurodegenerative WM changes in both the pre- and post-geniculate visual pathways of POAG patients. The pattern of changes suggests that glaucomatous WM degeneration starts at the pre-geniculate pathways and then spreads to the post-geniculate pathways. Furthermore, we find evidence that the trans-synaptic spread of glaucomatous degeneration to the post-geniculate pathways is a prolonged process which continues in the absence of detectable pre-geniculate degenerative progression. This suggests the presence of a time window for salvaging intact post-geniculate pathways, which could prove to be a viable therapeutic target in the future.

To classify CVI subtypes and compare the added value of an extensive test battery over a limited test battery in subtype classification of cerebral visual impairment (CVI) in children. Seventy-five children with a clinical diagnosis of CVI (median [IQR] age: 9 [7-12] years) were identified from the medical records. The extensive test battery included visual acuity, contrast sensitivity, ocular alignment, eye movement analysis, visual field analysis, optic nerve head evaluation, and evaluation of visual perception. The limited test battery included visual acuity, contrast sensitivity, ocular alignment, and evaluation of visual perception. Principal component analysis (PCA) followed by cluster analysis was done, for both test batteries separately, to determine the optimum subtype classification for CVI. Fifty-one participants with an extensive test battery with mild to moderate visual impairment were included in the main analysis. This resulted in four CVI subtypes for the extensive test battery (subtle characteristics, higher-level visual function deficits, lower-level visual function deficits, and higher- and lower- level visual function deficits) and three CVI subtypes for the limited test battery (subtle characteristics, higher-level visual function deficits, and higher- and lower- level visual function deficits). There were significant differences between the subtypes for 9 out of 10 measures of the extensive and all 4 measures of the limited test battery (  < 0.05). The subtle characteristics subtype (extensive  = 19, limited  = 15) showed near normal lower and higher-level visual functions in both test batteries. The higher-level visual function deficits subtype (extensive  = 18, limited  = 24) showed near normal visual acuity combined with significant visual perceptual deficits in both test batteries; accompanied by visual pathways defects and abnormal eye movement behavior in the extensive test battery. The higher- and lower- level visual function deficits subtype (extensive  = 4, limited  = 12) showed both higher and lower-level visual function deficits in both test batteries, but application of the extensive test battery revealed additional visual pathways defects and abnormal eye movement behavior. The lower-level visual function deficits CVI subtype (extensive  = 10) was a new subtype identified by the extensive test battery. This subtype showed lower-level visual function deficits together with abnormal eye movement measures. This data-driven study has provided meaningful CVI subtype classifications based on the outcomes of various key functional and structural measures in CVI diagnosis. Comparison of the extensive test battery to the limited test battery revealed the added value of an extensive test battery in classifying CVI. The outcomes of this study, therefore, have provided a new direction in the area of CVI classification.

Genetically complex ocular neuropathies, such as glaucoma, are a major cause of visual impairment worldwide. There is a growing need to generate suitable human representative in vitro and in vivo models, as there is no effective treatment available once damage has occured. Retinal organoids are increasingly being used for experimental gene therapy, stem cell replacement therapy and small molecule therapy. There are multiple protocols for the development of retinal organoids available, however, one potential drawback of the current methods is that the organoids can take between 6 weeks and 12 months on average to develop and mature, depending on the specific cell type wanted. Here, we describe and characterise a protocol focused on the generation of retinal ganglion cells within an accelerated four week timeframe without any external small molecules or growth factors. Subsequent long term cultures yield fully differentiated organoids displaying all major retinal cell types. RPE, Horizontal, Amacrine and Photoreceptors cells were generated using external factors to maintain lamination.

[This corrects the article DOI: 10.3389/fnins.2023.1266201.].

The degree to which glaucoma has effects in the brain beyond the eye and the visual pathways is unclear. To clarify this, we investigated white matter microstructure (WMM) in 37 tracts of patients with glaucoma, monocular blindness, and controls. We used brainlife.io for reproducibility. White matter tracts were subdivided into seven categories ranging from those primarily involved in vision (the visual white matter) to those primarily involved in cognition and motor control. In the vision tracts, WMM was decreased as measured by fractional anisotropy in both glaucoma and monocular blind subjects compared to controls, suggesting neurodegeneration due to reduced sensory inputs. A test–retest approach was used to validate these results. The pattern of results was different in monocular blind subjects, where WMM properties increased outside the visual white matter as compared to controls. This pattern of results suggests that whereas in the monocular blind loss of visual input might promote white matter reorganization outside of the early visual system, such reorganization might be reduced or absent in glaucoma. The results provide indirect evidence that in glaucoma unknown factors might limit the reorganization as seen in other patient groups following visual loss.