Search

PURPOSE: The aim of this study was to determine the association between caffeine intake and dry eye disease (DED) in the large, population-based LifeLines cohort in the Netherlands. METHODS: DED was cross-sectionally assessed in 85,302 participants (59% female participants) using the Women's Health Study dry eye questionnaire. Dietary caffeine was calculated from the intake of coffee, tea, cola, and energy drinks. Logistic regression was used to investigate the relationship between DED and caffeine, correcting for demographic variables, smoking status, alcohol intake, and 48 comorbidities of DED. RESULTS: The mean (SD; range) age of participants was 50.7 years (12.4; 18-96), and 50,339 (59%) were female. The mean (SD) caffeine intake was 285 (182) mg/d. After correcting for demographics, body mass index, smoking status, and alcohol intake, higher caffeine intake was associated with a decreased risk of Women's Health Study-defined DED [odds ratio (OR) 0.971 per 100 mg/d, 95% CI, 0.956-0.986, P < 0.0005]. When additionally adjusting for medical comorbidities, no significant effect was observed (OR 0.985, 95% CI, 0.969-1.001, P = 0.06). Caffeine's effect on DED was similar in male and female participants and independent of sleep quality and stress at work. Decaffeinated coffee intake was significantly associated with an increased risk of DED, when adjusted for caffeinated coffee, demographics, alcohol intake, smoking status, and comorbidities (OR 1.046 per cup/d, 95% CI, 1.010-1.084, P = 0.01). None of the beverages were significantly associated with the risk of DED, when correcting for intake of the other caffeinated beverages, demographics, smoking status, alcohol intake, and all comorbidities. CONCLUSIONS: Dietary caffeine intake does not seem to be a risk factor for DED in the general population.

As the histology, physiology, and pathophysiology of eyes and kidneys show substantial overlap, it has been suggested that eye and kidney diseases, such as glaucoma and chronic kidney disease (CKD), may be closely interlinked. We review the relationship between CKD and various subtypes of glaucoma, including primary open-angle glaucoma, primary angle- closure glaucoma, normal tension glaucoma, pseudoexfoliation syndrome, and several glaucoma endophenotypes. We also discuss the underlying pathogenic mechanisms and common risk factors for CKD and glaucoma, including atherosclerosis, the renin-angiotensin system, genes and genetic polymorphisms, vitamin D deficiency, and erythropoietin. The prevalence of glaucoma appears elevated in CKD patients, and vice versa, and the literature points to many intriguing associations; however, the associations are not always confirmed, and sometimes apparently opposite observations are reported. Glaucoma and CKD are complex diseases, and their mutual influence is only partially understood.

Purpose: To investigate the association of commonly used systemic medications with glaucoma and intraocular pressure (IOP) in the European population. Design: Meta-analysis of eleven population-based cohort studies of the European Eye Epidemiology (E3) consortium. Participants: A total of 143240 participants were included in the glaucoma analyses and 47177 participants in the IOP analyses. Methods: We examined associations of four categories of systemic medications (antihypertensive medications: beta-blockers, diuretics, calcium channel blockers [CCBs], alpha-agonists, angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers; lipid-lowering medications; antidepressants; antidiabetic medications) with glaucoma prevalence and IOP. Glaucoma ascertainment and IOP measurement method were according to individual study protocols. Multivariable regression analyses were carried out in each study and results were pooled using random effects meta-analyses. Associations with antidiabetic medications were examined in diabetic participants only. Main Outcome Measures: Glaucoma prevalence and IOP. Results: In the meta-analyses of our maximally-adjusted multivariable models, use of CCBs was associated with a higher prevalence of glaucoma (odds ratio [OR] with corresponding 95% confidence interval [95% CI]: 1.23 [1.08 to 1.39]). This association was stronger for monotherapy of CCBs with direct cardiac effects (OR [95% CI]: 1.96 [1.23 to 3.12]). The use of other antihypertensive medications, lipid-lowering medications, antidepressants or antidiabetic medications were not clearly associated with glaucoma. Use of systemic beta-blockers was associated with a lower IOP (Beta [95% CI]: -0.33 [-0.57 to -0.08] mmHg). Monotherapy of both selective (Beta [95% CI]: -0.45 [-0.74 to -0.16] mmHg) and non-selective (Beta [95% CI]: -0.54 [-0.94 to -0.15] mmHg) systemic beta-blockers was associated with lower IOP. There was a suggestive association between use of high-ceiling diuretics and lower IOP (Beta [95% CI]: -0.30 [-0.47; -0.14] mmHg), but not when used as monotherapy. Use of other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were not associated with IOP. Conclusions: We identified a potentially harmful association between use of CCBs and glaucoma prevalence. Additionally, we observed and quantified the association of lower IOP with systemic beta-blocker use. Both findings are potentially important given that glaucoma patients frequently use systemic antihypertensive medications. Determining whether the CCB association is causal should be a research priority. published

Secondary glaucoma is still a blinding complication in childhood uveitis, for which most commonly used surgical interventions (trabeculectomy or glaucoma drainage implant) involve multiple re-interventions and/or complications postoperatively. The goniotomy procedure has never been investigated in the current era, in which patients with pediatric uveitis receive biologics as immunosuppressive therapy for a prolonged period, with potential implications for the outcome. The purpose of the study is to evaluate the efficacy and safety of a goniotomy procedure in pediatric non-infectious uveitis in a retrospective, multicenter case series. The primary outcomes were the postoperative intraocular pressure (IOP), number of IOP-lowering medications, and success rate. Postoperative success was defined as 6 ≤ IOP ≤ 21 mmHg, without major complications or re-interventions. Fifteen eyes of ten children were included. Median age of the included patients at goniotomy was 7 years; median follow-up was 59 months. Median (interquartile range) IOP before surgery was 30 (26–34) mmHg with 4 (3–4) IOP-lowering medications. At 1, 2, and 5 years after goniotomy, median IOP was 15, 14, and 15 mmHg with 2 (0–2), 1 (0–2), and 0 (0–2) medications, respectively (p < 0.001 postoperatively versus preoperatively for all timepoints). Success rate was 100%, 93%, and 80% after 1, 2, and 5 years, respectively. There were no significant changes in visual acuity and uveitis activity or its treatment, and there were no major complications. Our results show that the goniotomy is an effective and safe surgery for children with uveitic glaucoma.

Purpose: To investigate the relationship between dry eye disease (DED) and vision-related quality of life (VR-QoL) at population level.Methods: DED and VR-QoL were assessed in 89,022 participants (18–96 years, 59% female) from the Dutch population-based Lifelines cohort using the Women's Health study (WHS) and Visual function 25 (VFQ25) questionnaires. The relationship between DED and compromised VR-QoL was assessed with logistic regression, corrected for age, sex, BMI, income, education, smoking, and 55 comorbidities.Results: 9.1% of participants had DED. The participants with DED had higher risk of compromised average of ten domains of VR-QoL (OR 3.12 (95% CI 2.98–3.27) corrected for age, sex, BMI, income, smoking, and 55 comorbidities). Increasing symptom frequency was highly associated with decreasing VR-QoL (P < 0.0005). In all VR-QoL domains, including measures of daily visual function and emotional well-being, DED was clearly associated with compromised VR-QoL. Compared to macular degeneration, glaucoma, retinal detachment, and allergic conjunctivitis, DED presented similar or higher risks for compromised score on all VR-QoL domains. The population-attributable fraction of DED for compromised general vision exceeded that of other eye diseases investigated, especially in the younger age groups.Conclusion: DED is associated with reductions in all domains of VR-QoL, also after correction for associated comorbidities. We found that DED imposes an extensive population burden regarding compromised VR-QoL due to its high prevalence and substantial impact on VR-QoL, higher than that for other common vision-affecting eye disorders. Our results emphasize the importance of recognizing DED as a serious disorder from both patient and public health perspectives.

Funding Information: We acknowledge all the participants and researchers of the 23 biobanks that have contributed to the GBMI. Biobank-specific acknowledgments are included in the Data S3 . We thank H. Huang, A.R. Martin, B.M. Neale, Y. Okada, K. Tsuo, J.C. Ulirsch, Y. Wang, and all the members of Finucane and Daly labs for their helpful feedback. M.K. was supported by a Nakajima Foundation Fellowship and the Masason Foundation . H.K.F. was funded by NIH grant DP5 OD024582 . Publisher Copyright: © 2022 The Author(s) Meta-analysis is pervasively used to combine multiple genome-wide association studies (GWASs). Fine-mapping of meta-analysis studies is typically performed as in a single-cohort study. Here, we first demonstrate that heterogeneity (e.g., of sample size, phenotyping, imputation) hurts calibration of meta-analysis fine-mapping. We propose a summary statistics-based quality-control (QC) method, suspicious loci analysis of meta-analysis summary statistics (SLALOM), that identifies suspicious loci for meta-analysis fine-mapping by detecting outliers in association statistics. We validate SLALOM in simulations and the GWAS Catalog. Applying SLALOM to 14 meta-analyses from the Global Biobank Meta-analysis Initiative (GBMI), we find that 67% of loci show suspicious patterns that call into question fine-mapping accuracy. These predicted suspicious loci are significantly depleted for having nonsynonymous variants as lead variant (2.7×; Fisher's exact p = 7.3 × 10−4). We find limited evidence of fine-mapping improvement in the GBMI meta-analyses compared with individual biobanks. We urge extreme caution when interpreting fine-mapping results from meta-analysis of heterogeneous cohorts.

Contains fulltext : 243957.pdf (Publisher’s version ) (Open Access) 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

Purpose: To date, population-based studies reporting associations between dry eye disease and medications were hypothesis-driven, did not take into account underlying comorbidities, and did not investigate individual drugs. The purpose of this study was to clarify the association of dry eye symptoms with medication classes and in-dividual drugs, using a hypothesis-free approach. Methods: 79,606 participants (age 20-97 years, 59.2% female) from the population-based Lifelines cohort in the Netherlands were cross-sectionally assessed for dry eye symptoms using the Womens' Health Study dry eye questionnaire. All medications used were coded with the ATC classification system. Logistic regression was used to assess the risk of the 59 most-used therapeutic/pharmacological subgroups and the 99 most-used individual drugs (all n > 200) on dry eye symptoms, correcting for age, sex, body mass index, and 48 comorbidities associated with dry eye. Results: Thirty-eight (64%) medication subgroups and fifty-two (53%) individual drugs were associated with dry eye symptoms (P < 0.05), after correction for age and sex only. A multivariable model correcting for comor-bidities revealed highly significant associations between dry eye symptoms and drugs for peptic ulcer (partic-ularly proton pump inhibitors (PPIs)), antiglaucoma and anticholinergic medications. Conclusions: This study underlines that medication use is highly informative of risk of dry eye symptoms. Correction for underlying comorbidities is critical to avoid confounding effects. This study confirms suggested associations between medications and dry eye symptoms at a population level and shows several new associa-tions. The novel link between PPIs and dry eye symptoms deserves particular attention given how commonly they are prescribed.

PURPOSE. Central corneal thickness (CCT) may be biologically related to glaucoma or observed as associated with glaucoma simply due to its effect on intraocular pressure (IOP) measurement. We aimed to determine if the previously reported CCT-glaucoma associations, in which the analyses were adjusted for IOP or participants were selected on IOP, could be explained by collider bias. METHODS. We simulated datasets mimicking a longitudinal population-based study (Los Angeles Latino Eye Study) and a trial (Ocular Hypertension Treatment Study) such that: (i) CCT was not truly associated with glaucoma, (ii) CCT and true IOP both contribute to measured IOP, and (iii) true IOP contributes to glaucoma risk.We then tested whether an association between CCT and glaucoma could be spuriously induced simply by adjusting for or selecting on measured IOP. RESULTS. A thinner CCT was significantly associated with higher glaucoma incidence in the simulated longitudinal population-based study when adjusted for measured IOP, but not crudely (unadjusted). A thinner CCT was crudely associated with glaucoma incidence in the simulated trial in which the participants were selected for high measured IOP. Effect sizes in the simulations were similar to those observed in the original studies. CONCLUSIONS. Our findings question whether CCT is biologically associated with glaucoma and suggest that current evidence may be due to collider bias. This indicates that CCT alone cannot be used as a factor to identify people at high risk of glaucoma in the general population. Using CCT in combination with IOP may be superior to using IOP alone.

Purpose: OCT can be used for glaucoma assessment, but its usefulness may depend on image quality, disease stage and segmentation algorithm. We aimed to determine how layer thicknesses as assessed with different algorithms depend on image quality and disease stage, how reproducible the algorithms are, and if the algorithms (dis)agree.Methods: Optic disc OCT data (Canon OCT-HS100) from 20 healthy subjects and 28 early, 29 moderate, and 23 severe glaucoma patients were assessed with four different algorithms (CANON, IOWA, FWHM, DOCTRAP). We measured retinal nerve fibre layer thickness (RNFLT) and total retinal thickness (TRT) along the 1.7-mm-radius OCT measurement circle centred at the optic disc. In healthy subjects, image quality was degraded with neutral density filters (0.3–0.9 optical density [OD]); three scans were made to assess repeatability.Results were analysed with ANOVA with Bonferroni corrected t-tests for post hoc analysis and with intraclass correlation coefficient (ICC) analysis. Results: For all algorithms, RNFLT was more sensitive to image quality than TRT. Both RNFLT and TRT showed differences between healthy and glaucoma (all algorithms p < 0.001 for both RNFLT and TRT) and between early and moderate glaucoma (RNFLT: p = 0.001 to p = 0.09; TRT: p < 0.001 to p = 0.03); neither was able to discriminate between moderate and severe glaucoma (p = 0.08 to p = 1.0). Generally, repeatability was excellent (ICC >0.75); agreement between algorithms varied from moderate to excellent.Conclusions: OCT becomes less informative with glaucoma progression, irrespective of the algorithm. For good-quality scans, RNFLT and TRT perform similarly; TRT may be advantageous with poor image quality.

Purpose To assess the association between dry eye disease (DED) and alcohol consumption using a large population-based cohort. Methods 77,145 participants (19–94 years, 59% female) from the Dutch Lifelines cohort were cross-sectionally assessed for DED using the Women's Health Study (WHS) dry eye questionnaire. Alcohol intake was assessed using self-reported food frequency questionnaires. The relationship between DED and alcohol use was analyzed using logistic regression, corrected for age, sex, BMI, smoking status, education, income, and 55 potentially confounding comorbidities. Results Overall, 30.0% of participants had symptomatic dry eye. Alcohol use significantly increased the risk of symptomatic dry eye in females (odds ratio [OR] 1.095, 95%CI 1.045–1.148), but not in males (OR 0.988, 95%CI 0.900–1.084). Contrarily, in male drinkers, increasing alcohol intake (in 10 g/day) had a protective effect on symptomatic dry eye (OR 0.962, 95%CI 0.934–0.992), which was not seen in females (OR 0.986, 95%CI 0.950–1.023). Alcohol use and intake had a sex-specific effect on all outcomes of DED assessed: symptomatic dry eye, highly symptomatic dry eye, clinical diagnosis, and WHS definition dry eye. Conclusions This large population-based study found alcohol use to have a clear sex-specific effect on DED, presenting as a risk-factor only in females. This adds to the evidence of sex-specific pathophysiological mechanisms of dry eye and illustrates the importance of sex stratification in studies investigating DED. The mild protective effect of increased alcohol intake in male drinkers is advised to be interpreted with caution, as alcohol's other health effects might be of greater clinical significance.

Purpose: To improve upon self-reported glaucoma status in population-based cohorts by developing a questionnaire-based proxy incorporating self-reported status in conjunction with glaucoma-specific visual complaints. Methods: A vision specific questionnaire, including questions from the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) was administered to 79,866 Lifelines participants, a population-based cohort study in the Northern Netherlands. We compared NEI-VFQ-25 responses between ‘definite’ glaucoma cases (n = 90; self-reported surgical cases) and an age- and gender-matched subset of controls (n = 1,800) to uncover glaucoma-specific visual complaints, using a case–control logistic regression. We defined ‘probable glaucoma’ as both self-reported disease status and visual complaints, and ‘possible glaucoma’ as either. To evaluate the resulting proxy, we determined age-stratified glaucoma prevalences in the remaining cohort and compared the result to the literature. Results: Per unit increase in the vision subscales (range 0–100) distance, peripheral and low luminance, we observed significantly increased odds of definite glaucoma (2% [P = 0.03], 4% [P = 1.2 × 10−8] and 2% [P = 0.02], respectively); the associated area under the curve was 0.73. We identified 300 probable and 3,015 (1,434 by self-report) possible glaucoma cases. Standardised prevalences of definite, probable and possible glaucoma for 55+ were 0.4%, 1.1% and 7.3%, respectively. For self-reported glaucoma (combining definite, probable and possible by self-report), this was 5.2%. Conclusions: The combination of self-reported glaucoma status and visual complaints can be used to capture glaucoma cases in population-based settings. The resulting prevalence of combined definite and probable glaucoma (1.5%) appears to be more consistent with previous reports than the prevalence estimate of 5.2% based only on self-report.

Purpose This study explores the effect of glaucomatous visual field defects on several neuropsychological tests that are often used in research and in clinical settings. Methods Nineteen glaucoma patients and nineteen healthy participants, which are current drivers and older than 65 years old were included. All participants completed the Montreal Cognitive Assessment (MoCA), the Trail Making Test (TMT), the Benton Visual Retention Test (BVRT), the Snellgrove Maze Task (SMT) and the Digit Span Test (DST). All participants were also tested on contrast sensitivity and near and far visual acuity. For the glaucoma patients, visual field tests were downloaded from hospital servers. Results On the MoCA test, glaucoma patients scored lower than the healthy group, but not significantly. On the MoCA-Blind, the difference was statistically significant. Glaucoma patients also had lower percentile scores on the TMT, with a significant difference in the TMT-A, but this difference largely disappeared in the calculated TMT B-A index, which isolates the cognitive component. The BVRT and SMT showed no significant differences between both groups. In the only non-visual test, the DST, glaucoma patients outperformed the healthy group. Glaucoma severity did not influence results, except for the BVRT on which the moderate/severe group has better scores. Conclusion Using visual items might lead to conclusions about cognition when it should be one about vision. Therefore, careful selection of tests is needed when examining cognition in glaucoma patients.

This review aims to evaluate the role of hyperreflective dots (HRDs), detected using OCT, as a predictor of the treatment outcome in patients with diabetic macular edema (DME).The treatment of DME is possible, but its results are often unsatisfactory. Thus, it is important to develop biomarkers that can help to predict the treatment response to optimize the treatment's effect for individual patients.PubMed, Embase, Web of science, and Cochrane library were searched (final search date on May 5, 2021). Participants were patients diagnosed with DME and provided with treatment. The predictor was HRDs, detected using OCT, before treatment. The outcomes were best-corrected visual acuity (BCVA) and central macular thickness (CMT), detected using OCT, after treatment. Two reviewers independently screened the titles and abstracts as well as full text. The refined Quality in Prognosis Studies tool was used to assess the risk of bias for each included study. Because of the clinical heterogeneity of the studies, a meta-analysis was not performed.Thirty-six studies were included. The Quality in Prognosis Studies assessment showed that most studies had a low or moderate risk of bias in 6 domains. Six studies could not find any correlation between baseline HRDs (either the presence or absence of HRDs [n = 1] or baseline HRD number [n = 5]) and outcome (BCVA or CMT), whereas 12 studies found a significant correlation between these variables. Eight studies reported that baseline HRDs could predict a poor visual outcome (n = 4 on prescence or abscence of HRD and n = 4 on HRD number), and 4 studies (n = 1 on prescence or abscence of HRD and n = 3 on HRD number) found that HRDs were predictive of visual improvement. Fifteen out of 17 studies found that the HRD number decreased after treatment.Based on the current literature, the HRD numbers decrease with treatment, but it is not clear whether HRDs predict the treatment outcome in patients with DME. Future investigations with more uniform approaches are needed to confirm the nature of this biomarker and its effect on DME treatment outcome.

PurposeTo compare retinal oxygen delivery (DO2) and extraction (VO2) in ophthalmologically healthy subjects with different blood pressure (BP) status.MethodsIn this case-control study, we prospectively included 93 eyes of 93 subjects (age 50-65) from a large-scale population-based Dutch cohort (n=167,000) and allocated them to four groups (low BP, normal BP [controls], treated arterial hypertension [AHT], untreated AHT). We estimated vascular calibers from fundus images and fractal dimension (FD) from optical coherence tomography angiography scans. We combined calibers, FD, BP, and intraocular pressure measurements in a proxy of total retinal blood flow (RBF), using a validated Poiseuille-based model. We measured arterial and venous oxygen saturations (SaO2, SvO2) with a two-wavelength scanning laser ophthalmoscope. We calculated DO2 and VO2 from RBF, SaO2, and SvO2. We compared DO2 and VO2 between groups and investigated the DO2-VO2 association.ResultsDO2 and VO2 were different between groups (P=0.009, P=0.036, respectively). In post hoc analysis, the low BP group had lower DO2 than the untreated AHT group (P=4.9·10-4), while both the low BP group and the treated AHT group had lower VO2 than the untreated AHT group (P=0.021, P=0.034, respectively). There was a significant DO2-VO2 correlation (Robs=0.65, bobs=0.51, P=2.4·10-12). After correcting for shared measurement error, the slope was no longer significant (bcor=0.19, P=0.29), while the correlation coefficient could not be calculated.ConclusionsDO2 and VO2 were altered in ophthalmologically healthy subjects with different BP status. Future studies could elucidate whether these changes can explain the increased risk of several ophthalmic pathologies in those subjects.

PURPOSE. In glaucoma, visual field defects in the left and right eye may be non-overlapping, resulting in an intact binocular visual field. In clinical management, these patients are often considered to have normal vision. However, visual performance also relies on binocular processing. The aim of this study was to evaluate binocular visual functions in glaucoma patients with intact binocular visual field, normal visual acuity, and stereoscopy.METHODS. We measured in 10 glaucoma patients and 12 age-similar controls: (1) monocular and binocular contrast sensitivity functions (CSF) using a modified quick CSF test to assess binocular contrast summation, (2) dominance during rivalry, and (3) contrast ratio at balance point with a binocular phase combination test. A mirror stereoscope was used to combine the left and right eye image (each 10 degrees horizontally by 12 degrees vertically) on a display.RESULTS. Area under the monocular and binocular CSF was lower in glaucoma compared to healthy (P < 0.001), but the binocular contrast summation ratio did not differ (P = 0.30). For rivalry, the percentage of time of mixed percept was 9% versus 18% (P = 0.056), the absolute difference of the percentage of time of dominance between the two eyes 19% versus 10% (P = 0.075), and the rivalry rate 8.2 versus 12.1 switches per minute (P = 0.017) for glaucoma and healthy, respectively. Median contrast ratio at balance point was 0.66 in glaucoma and 1.03 in controls (P = 0.011).CONCLUSIONS. Binocular visual information processing deficits can be found in glaucoma patients with intact binocular visual field, normal visual acuity, and stereoscopy.

Funding Information: The work of the contributing biobanks was supported by numerous grants from governmental and charitable bodies. Biobank-specific acknowledgments and more detailed acknowledgments are included in Data S2. Initiative management, S.B.C. J.C. N.J.C. M.J.D. E.E.K. A.R.M. B.M.N. Y.O. A.V.P. D.A.v.H. R.G.W. C.J.W. W.Z. and S.Z.; individual biobank analysis, A.B. Y.B. B.M.B. C.D.B. S.C. T.-T.C. K.C. S.M.D. M.D. G.H.d.B. Y.D. N.J.D. M.-J.F. Y.-C.A.F. S.F. V.L.F. L.G.F. E.R.G. T.R.G. D.H.G. C.R.G. G.G.-A. S.E.G. L.A.G. C.H. J.B.H. W.E.H. H.H. K.H. N.I. A.I. R.J. M. Kurki, J.K. N.K. E.E.K. J.T.K. M. Kanai, T.L. K.L. M.H.L. S.L. K.L. Y.-F.L. V.L.F. R.J.F.L. E.A.L.-M. A.R.-M. S.M.-G. R.M. R.E.M. H.C.M. A.R.M. Y.M. H.M. S.E.M. I.Y.M. B.M. S.M. K.N. S.N. M.A.N.-A. K.N. Y.O. P.P. A.L.-P. A.P. B.P. S.P. M.H.P. D.J.R. N.R. M.D.R. A.R. C.S. S.S. S.S.S. J.A.S. P.S. I.S. T.T. R.T. K.T. J.U. D.A.v.H. B.V. M.V. Y.V. J.M.V. R.G.W. Y.W. S.J.W. B.N.W. K.-H.H.W. M.Z. X.Z. and S.Z.; individual biobank management, N.A. A.A.T. K.M.A.-D. P.A. K.C.B. M. Boehnke, M. Boezen, C.D.B. A.C. Z.C. C.-Y.C. J.C. N.J.C. S.M.D. S.F. Y.-C.A.F. S.F. E.F. T.G. C.R.G. C.J.G. Y.G. H.H. K.A.H. K.H. S.I.I. N.M.J. N.K. E.E.K. J.T.K. C.L. M.H.L. M.T.M.L. L.L. K.L. Y.-F.L. R.J.F.L. J.L. S.M. Y.M. K.M. I.Y.M. Y.O. C.M.O. A.V.P. B.P. D.J.P. D.J.R. M.D.R. S.S. J.W.S. H.S. K.S. T.T. U.T. R.C.T. D.A.v.H. M.V. R.G.W. D.C.W. C.W. J.W. M.Z. X.Z. and S.Z.; study design and interpretation of results, A.B. M. Boehnke, M. Boezen, B.M.B. T.-T.C. C.-Y.C. M.J.D. G.D.S. N.J.D. S.F. M.-J.F. H.K.F. E.R.G. A.G. T.G. J.B.H. J.H. K.H. R.J. M.K. E.E.K. T.K. C.M.L. V.L.F. E.A.L.-M. A.R.M. S.N. B.M.N. C.M.O. J.J.P. B.P. N.R. H.R. J.A.S. I.S. K.T. D.A.v.H. R.G.W. Y.W. D.C.W. S.J.W. C.J.W. B.N.W. J.W. K.-H.H.W. M.Z. H.Z. J.Z. W.Z. X.Z. and S.Z.; drafted and edited the paper, A.B. M. Boehnke, M. Boezen, M.J.D. G.H.d.B. N.J.D. T.R.G. J.B.H. N.I. N.M.J. M.K. V.L.F. S.M. A.R.M. H.M. S.N. B.M.N. C.M.O. B.P. H.R. C.S. J.A.S. J.W.S. K.T. Y.W. D.C.W. C.J.W. K.-H.H.W. H.Z. J.Z. W.Z. and S.Z.; primary meta-analysis and quality control, M.J.D. H.K.F. M. Kanai, J.K. J.T.K. M. Kurki, M.M. B.M.N. C.J.W. K.-H.H.W. and W.Z.; drug discovery: S.N. T.K. K.-H.H.W. W.Z. and Y.O.; fine mapping, M. Kanai, W.Z. M.J.D. and H.K.F.; polygenic risk score, Y.W. S.N. E.A.L.-M. S.K. K.T. K.L. M. Kanai, W.Z. K.W. M.-J.F. L.B. P.A. P.D. V.L.F. R.M. Y.M. B.B. S.S. J.U. E.R.G. N.J.C. I.S. Y.O. A.R.M. and J.B.H.; proteome-wide Mendelian randomization, H.Z. H.R. A.B. G.H. G.D.S. B.M.B. W.Z. B.M.N. T.R.G. and J.Z.; transcriptome-wide association study, A.B. J.B.H. W.Z. J.Z. M. Kanai, B.P. E.R.G. and N.J.C.; asthma, K.T. W.Z. Y.W. M. Kanai, S.N. Y.O. B.M.N. M.J.D. and A.R.M.; heart failure, K.-H.H.W. N.J.D. B.N.W. I.S. S.E.G. J.B.H. N.J.C. M.P. R.J.F.L. M.J.D. B.M.N. W.Z. W.E.H. and C.J.W.; idiopathic pulmonary fibrosis, J.J.P. W.Z. M.J.D. J.T.K. N.J.C. and J.B.H.; primary open-angle glaucoma, V.L.F. A.B. W.Z. Y.W. K.L. M. Kanai, E.A.L.-M. P.S. R.T. X.Z. S.N. S.S. Y.O. N.I. S.M. H.S. I.S. C.W. A.R.M. E.R.G. N.M.J. N.J.C. and J.B.H.; stroke, I.S. K.-H.H.W. W.H. B.N.W. W.Z. J.E.H. A.P. B.B. A.H.S. M.E.G. R.G.W. K.H. C.K. S.Z. M.J.D. B.M.N. and C.J.W.; venous thromboembolism, B.N.W. I.S. K.-H.H.W. B.B. V.L.F. K.T. M.D. B.N. W.Z. J.A.S. and C.J.W. All authors reviewed the manuscript. M.J.D. is a founder of Maze Therapeutics. B.M.N. is a member of the scientific advisory board at Deep Genomics and a consultant for Camp4 Therapeutics, Takeda Pharmaceutical, and Biogen. The spouse of C.J.W. works at Regeneron Pharmaceuticals. C.-Y.C. is employed by Biogen. C.R.G. owns stock in 23andMe, Inc. T.R.G. has received research funding from various pharmaceutical companies to support the application of Mendelian randomization to drug target prioritization. E.E.K. has received speaker fees from Regeneron, Illumina, and 23andMe and is a member of the advisory board for Galateo Bio. R.E.M. has received speaker fees from Illumina and is a scientific advisor to the Epigenetic Clock Development Foundation. G.D.S. has received research funding from various pharmaceutical companies to support the application of Mendelian randomization to drug target prioritization. K.S. and U.T. are employed by deCODE Genetics/Amgen, Inc. J.Z. has received research funding from various pharmaceutical companies to support the application of Mendelian randomization to drug target prioritization. S.M. is a co-founder of and holds stock in Seonix Bio. Publisher Copyright: © 2022 Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)—a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits.

Contains fulltext : 282598.pdf (Publisher’s version ) (Open Access) PURPOSE: Primary congenital glaucoma (PCG) is a form of childhood glaucoma caused by maldevelopment of the anterior chamber. Disease severity differs greatly amongst patients. Ultrasound biomicroscopy (UBM) is a non-invasive technique that can visualize the anterior segment in infants in vivo. The purpose of this narrative review is to make an overview of the UBM data in PCG and study the applicability of UBM in characterizing the disease. METHODS: An online search was performed on PubMed in December 2020. After a critical appraisal of the included articles, study and patient characteristics were summarized. The UBM measurements of the anterior segment in PCG of the different studies were analysed. RESULTS: Six studies were included in this review. All were cross-sectional prospective studies. A total of 221 PCG eyes were examined. PCG eyes showed a larger trabecular iris angle, decreased iris thickness, narrower or absent Schlemm's canal and an increased zonular length compared to controls. Abnormal tissue membrane covering the trabecular meshwork and abnormal insertion of the iris and ciliary process were frequently found. The success rate of glaucoma surgery depended on the severity of anterior segment malformations found with UBM. CONCLUSION: Malformations of the anterior segment in PCG can be demonstrated by UBM in vivo. This imaging can help to characterize disease severity and might support surgical treatment decisions.

We have systematically extracted all available heritability (h2) estimates of glaucoma and related endophenotypes from the literature and summarized the evidence by meta-analysis. Glaucoma endophenotypes were classified into 10 clusters: intraocular pressure, anterior chamber size, central corneal thickness, cup-to-disc ratio, disc size, cup size, corneal hysteresis, retinal nerve fiber layer thickness, cup shape, and peripapillary atrophy. Random-effects meta-analyses were performed for each cluster. For clusters with n ≥ 10 h2 estimates, we also performed subgroup and meta-regression analyses. The literature search yielded 53 studies. The h2 of primary open-angle glaucoma ranged from 0.17 to 0.81, and was 0.65 for primary angle-closure glaucoma in a single study. The pooled endophenotype h2 estimates were intraocular pressure, 0.43 (0.38-0.48); anterior chamber size, 0.67 (0.60-0.74); central corneal thickness, 0.81 (0.73-0.87); cup-to-disc ratio, 0.56 (0.44-0.68); disc size, 0.61 (0.37-0.81); cup size, 0.58 (0.35-0.78); corneal hysteresis, 0.40 (0.29-0.51); retinal nerve fiber layer thickness, 0.73 (0.42-0.91); cup shape, 0.62 (0.22-0.90); and peripapillary atrophy, 0.73 (0.70-0.75). We identified mean age, ethnicity, and study design as major sources of heterogeneity. Our results confirm the strong influence of genetic factors on glaucoma and its endophenotypes. These pooled h2 estimates provide the most accurate assessment to date of the total genetic variation that can ultimately be explained by gene-finding studies.

Purpose: White matter (WM) degeneration of the visual pathways in primary open-angle glaucoma (POAG) is well documented, but its exact pathophysiology remains unclear. To date, glaucomatous WM degeneration has been exclusively studied using diffusion tensor imaging (DTI) only. However, DTI measures lack direct biological interpretation, and the approach itself suffers from multiple technical limitations. Fixel-based analysis (FBA) is a novel framework for studying WM degeneration, overcoming DTI's technical limitations and providing biologically meaningful metrics. FBA measures fiber density (FD), representing early microstructural changes, and fiber-bundle cross section (FC), representing late macrostructural changes. In this study, we use FBA to study glaucomatous degeneration of the pregeniculate optic tracts (OTs) and postgeniculate optic radiation (ORs) in POAG.Methods: This was a cross-sectional case-control study with 12 POAG patients and 16 controls. Multi-shell diffusion-weighted images were acquired. FBA was used to produce a population template, and probabilistic tractography was used to track the OTs and ORs in template space. Finally, FD and FC of the tracts of interest were compared between the two groups.Results: Compared with the controls, the OTs of the patients exhibited a significant (familywise error corrected P Conclusions: FBA provides sensitive measures to assess WM changes in glaucoma. Our findings suggest that the OTs of glaucoma patients exhibit signs of more advanced WM degeneration compared with the ORs. This potentially implicates anterograde trans-synaptic propagation as the primary cause of glaucomatous spread along the visual pathways.

Introduction: Environmental factors play an important aetiological role in dry eye.This cross-sectional study investigated the relationship between types of occupation and symptomatic dry eye.Methods: 40,501 employed people working >= 8 h a week were included from the population-based Lifelines cohort in the Netherlands. Logistic regression was used to determine the association between symptomatic dry eye (assessed by the WHS questionnaire) and occupation (using the ISCO-08 classification system).Results: After correction for age and sex, the professionals (e.g. legal, health, and business and administration professionals) (OR = 1.14, 95%CI = 1.08-1.19, P Conclusions: This study underlines the importance of asking about type of occupation in dry eye patients. Screening for symptomatic dry eye in high risk occupations such as in building workers and in indoor occupations with high screen use is relevant from an occupational health and work productivity perspective. The lower risk of dry eye in outdoor and active occupation is intriguing and justifies future studies to investigate potential protective and treatment effects.

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.

Purpose To determine the cost (loss of visual function associated with the procedure) and benefit (long-term preservation of the visual field) of glaucoma surgery. Methods We included 100 patients who underwent glaucoma surgery (Baerveldt glaucoma implant [BGI], n = 61; trabeculectomy [TE], n = 39). Preoperatively, the median (interquartile range [IQR]) standard automated perimetry mean deviation (MD) was -12 (-16 to -6) dB. We analysed the change in visual acuity (BCVA) and MD due to the procedure and, in a subset with at least 5 years of perimetric follow-up both pre- and postoperatively (n = 20), the change in rate of progression (ROP; time rate of change in MD). For the surgery-induced change in ROP, we also performed a meta-analysis including the current and previously published studies. From the surgery-induced decrease in MD and change in ROP, we calculated the average postoperative duration needed for the benefit to surpass the cost. Results Mean (standard deviation) MD decline was 1.3 (2.7) and 1.0 (2.3) dB for BGI (p

Glaucoma is a chronic progressive optic neuropathy that causes visual impairment or blindness if left untreated. It is crucial to diagnose it at an early stage in order to enable treatment. Fundus photography is a viable option for population-based screening. A fundus photograph enables the observation of the excavation of the optic disk—the hallmark of glaucoma. The excavation is quantified as a vertical cup-to-disk ratio (VCDR). The manual assessment of retinal fundus images is, however, time-consuming and costly. Thus, an automated system is necessary to assist human observers. We propose a computer-aided diagnosis system, which consists of the localization of the optic disk, the determination of the height of the optic disk and the cup, and the computation of the VCDR. We evaluated the performance of our approach on eight publicly available datasets, which have, in total, 1712 retinal fundus images. We compared the obtained VCDR values with those provided by an experienced ophthalmologist and achieved a weighted VCDR mean difference of 0.11. The system provides a reliable estimation of the height of the optic disk and the cup in terms of the relative height error (RHE = 0.08 and 0.09, respectively). The Bland–Altman analysis showed that the system achieves a good agreement with the manual annotations, especially for large VCDRs which indicate pathology.

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.

AimsTo build a questionnaire-based myopia proxy and to validate the proxy by confirming its association with educational attainment and a Polygenic Risk Score (PRS) for myopia.MethodsData were collected between 2014 and 2017 from 88 646 Dutch adults from the LifeLines Cohort. First, we performed principal component analysis (PCA) to responses of five refraction-status questions. Second, we measured the refractive state in a subset of LifeLines participants (n=326) and performed logistic regression using myopia (mean spherical equivalent ResultsA total of 77 096 participants (58.1% women) were eligible for the PCA. The first two PCs had a specificity of 91.9% (95% CI 87.8% to 95.4%) and a sensitivity of 90.4% (95% CI 84.3% to 96.4%) for myopia. The area under the receiver operating characteristic curve was 95.0% (95% CI 92.2% to 97.8%). The age-standardised prevalence of proxy-inferred myopia was 33.8% (95% CI 33.4% to 34.3%). Compared with low education level, the ORs of proxy-inferred myopia were 1.66 (95% CI 1.58 to 1.74, p=5.94×10−90) and 2.54 (95% CI 2.41 to 2.68, p=4.04×10−271) for medium and high education levels, respectively. Similarly, individuals at the top 10% of PRS (vs lower 90%) had an OR of 2.18 (95% CI 1.98 to 2.41, p=6.57×10−56) for proxy-inferred myopia, whereas those at the highest decile had an OR of 4.51 (95% CI 3.9 to 5.21, p=1.74×10−89) when compared with the lowest decile.ConclusionSelf-administered refractive error-related questions could be used as an effective tool to capture proxy-inferred myopic cases in a population-based setting.

Objective1) To investigate the effect of low blood pressure (BP), treated arterial hypertension (AHT), and untreated AHT on the ganglion cell-inner plexiform layer (GCIPL) and the retinal nerve fiber layer (RNFL) thickness of non-glaucomatous eyes and 2) to elucidate whether this effect is related to crossing the lower limit of retinal blood flow (RBF) autoregulation.DesignCross-sectional, case-control.SubjectsWe included 96 eyes of 96 ophthalmologically healthy subjects (age 50-65). Participants were prospectively recruited from a large-scale cohort study in the northern Netherlands (n=167,000; Lifelines Biobank). They were allocated to four groups (low BP, normal BP [controls], treated AHT, untreated AHT), based on information from previous visits and strict distribution criteria.MethodsInner retinal layer thicknesses were obtained with optical coherence tomography (OCT). Fractal dimension of the superficial microvasculature was quantified with OCT-angiography and customized software. Central retinal vessel diameters were obtained from fundus images. BP and intraocular pressure measurements were also acquired. Measurements were combined with a validated physiological model to estimate vascular outcome measures. Structural and vascular metrics were compared across groups and mediation analysis was performed.Main outcome measuresStructural: macular GCIPL and RNFL (mRNFL), peripapillary RNFL (pRNFL) thickness. Vascular: RBF, retinal vascular resistance (RVR), autoregulatory reserve (AR).ResultsCompared to controls, GCIPL was thinner in the low BP group (P=0.013), treated hypertensives (P=0.007), and untreated hypertensives (P=0.007). Treated hypertensives exhibited the thinnest mRNFL (P=0.001), temporal pRNFL (P=0.045), and inferior pRNFL (P=0.034). In multivariable analysis, RBF was mediating the association of GCIPL thickness with BP within the combined low BP group and controls (P=0.003), RVR together with AR were mediating the same association within the combined treated hypertensives and controls (P=0.001 and P=0.032), and RVR was mediating the association within the combined untreated antihypertensives and controls (P=0.022).ConclusionsWe uncovered GCIPL and RNFL thinning related to both tails of the BP distribution. GCIPL thinning was associated with reduced RBF autoregulatory capacity. This predisposition to glaucomatous damage could explain the frequent epidemiological finding of increased glaucoma risk in certain subgroups, such as subjects with nocturnal BP dipping or aggressively treated AHT. Longitudinal studies could confirm this postulation.

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.

Background Early detection of glaucoma is paramount to maintain patients’ eyesight, however glaucomatous vision loss tends to begin in the periphery with up to 50% of patients unaware they are affected. Because glaucomatous vision loss is permanent, screening appears attractive, but currently is not cost-effective. Therefore we aim to investigate the utility of genetic pre-screening for glaucoma in a population-based setting, called EyeLife. Methods EyeLife adopts a double blind prospective design with contrasting groups. Selected participants (n = 1600) from the Lifelines cohort are 55 years of age or older, and of either the highest or lowest 20% of the genetic risk distribution for glaucoma. We obtained a highly curated list of genetic variants from the literature to obtain each participants’ genetic risk for glaucoma. Participants will undergo comprehensive ophthalmic screening. The primary outcome is the relative risk of glaucoma given a high genetic risk compared to a low genetic risk. Discussion If genetic pre-screening is successful, it will increase the yield of a glaucoma screening program by focusing on high-risk individuals. This, in turn, may improve long-term visual health of middle-aged and elderly people. Trial registration Ethics approval was obtained on January 31, 2019, and the study was retrospectively registered with the Netherlands Trial Register (NL8718) on the 17th of June, 2020.

This file is supplementary material to:Pappelis K, Choritz L, Jansonius NM. Microcirculatory model predicts blood flow and autoregulation range in the human retina: in vivo investigation with Laser Speckle Flowgraphy. Am J Physiol Heart Circ Physiol. 2020 Dec 1;319(6):H1253-1273

PurposeTo evaluate the accuracy and reliability of functional magnetic resonance imaging (fMRI)-based techniques to assess the integrity of the visual field (VF).MethodsWe combined fMRI and neurocomputational models, i.e conventional population receptive field (pRF) mapping and a new advanced pRF framework “micro-probing” (MP), to reconstruct the visual field representations of different cortical areas. To demonstrate their scope, both approaches were applied in healthy participants with simulated scotomas (SS) and participants with glaucoma. For the latter group we compared the VFs obtained with standard automated perimetry (SAP) and via fMRI.ResultsUsing SS, we found that the fMRI-based techniques can detect absolute defects in VFs that are larger than 3 deg, in single participants, and based on 12 minutes of fMRI scan time. Moreover, we found that MP results in a less biased estimation of the preserved VF. In participants with glaucoma, we found that fMRI-based VF reconstruction detected VF defects with a correspondence to SAP that was decent, reflected by the positive correlation between fMRI-based sampling density and SAP-based contrast sensitivity loss (SAP) r2=0.44, p=0.0002.This correlation was higher for our new approach (MP) compared to that for the conventional pRF analysis.ConclusionsfMRI-based reconstruction of the VF enables the evaluation of vision loss and provides useful details on the properties of the visual cortex.Translational RelevancefMRI-based VF reconstruction provides an objective alternative to detect VF defects. It may either complement SAP, or could provide VF information in patients unable to perform SAP.

The degree to which glaucoma has effects beyond the eye –in the brain– is unclear. We investigated white matter microstructure (WMM) alterations in 37 tracts of patients with glaucoma, monocular blindness and controls. We used reproducible methods and the advanced cloud computing platform brainlife.io. White matter tracts were subdivided into seven categories ranging from primarily involved in vision (the visual white matter) to primarily involved in cognition and motor control. WMM in both glaucoma and monocular blind subjects was lower than controls in the visual white matter, suggesting neurodegenerative mechanisms due to reduced sensory inputs. In glaucoma participants WMM differences from controls decreased outside the visual white matter. A test-retest validation approach was used to validate these results. The pattern of results was different in monocular blind participants, where WMM properties increased outside the visual white matter as compared to controls. The pattern of results suggests that whereas in the 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 brain plasticity effects that in other patient groups follow visual loss.

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.