Association between primary angle closure glaucoma and uric acid levels in serum and aqueous humor.

Purpose: To evaluate abnormalities in serum and aqueous humor uric acid (UA) levels in primary angle closure glaucoma (PACG). Methods: Patients with PACG and age-similar and gender-similar controls (patients scheduled for cataract extraction) were enrolled prospectively. Serum UA levels were determined by enzymatic colorimetry; aqueous humor UA levels by Enzyme-Linked ImmunoSorbent Assay. A t-test was used to compare UA levels between PACG patients and controls, with one-way ANOVA used to compare levels across PACG subgroups with differing disease severity. Comparisons between PACG patients and controls were adjusted for systemic and ocular confounding factors using binary logistic regression. Results: In all, 131 PACG patients and 112 controls were included. The serum UA level was 266 ± 69 µmol/L in the PACG group and 269 ± 73 µmol/L in the control group (p = 0.71). The aqueous humor UA level was 35.4 ± 8.2 µmol/L in the PACG group and 53.9 ± 18.6 µmol/L in the control group (p < 0.001). This difference remained significant after adjusting for age, gender, systolic blood pressure, diastolic blood pressure, body mass index, axial length, central corneal thickness, anterior chamber depth, lens thickness, white-to-white distance, corneal endothelial cell density, and serum UA level (odds ratio: 0.88, 95 % confidence interval: 0.83-0.93, p < 0.001). Conclusion: Aqueous humor UA levels differ between PACG patients and controls, but serum UA levels do not. This indicates that local UA plays a role in the pathogenesis of PACG, but systemic UA does not.

Reduced Thickness of the Retina in de novo Parkinson's Disease Shows A Distinct Pattern, Different from Glaucoma.

Background: Parkinson's disease (PD) patients experience visual symptoms and retinal degeneration. Studies using optical coherence tomography (OCT) have shown reduced thickness of the retina in PD, also a key characteristic of glaucoma. Objective: To identify the presence and pattern of retinal changes in de novo, treatment-naive PD patients compared to healthy controls (HC) and early primary open angle glaucoma (POAG) patients. Methods: Macular OCT data (10×10 mm) were collected from HC, PD, and early POAG patients, at the University Medical Center Groningen. Bayesian informative hypotheses statistical analyses were carried out comparing HC, PD-, and POAG patients, within each retinal cell layer. Results: In total 100 HC, 121 PD, and 78 POAG patients were included. We showed significant reduced thickness of the inner plexiform layer and retinal pigment epithelium in PD compared to HC. POAG patients presented with a significantly thinner retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, outer plexiform layer, and outer photoreceptor and subretinal virtual space compared to PD. Only the outer segment layer and retinal pigment epithelium were significantly thinner in PD compared to POAG. Conclusions: De novo PD patients show reduced thickness of the retina compared to HC, especially of the inner plexiform layer, which differs significantly from POAG, showing a more extensive and widespread pattern of reduced thickness across layers. OCT is a useful tool to detect retinal changes in de novo PD, but its specificity versus other neurodegenerative disorders has to be established.

The 6-Item Vision-Related Quality of Life and Limitations Questionnaire: Evaluation of Psychometric Properties.

Purpose: We developed the Vision-related Quality of life and Limitations Questionnaire (VQL-6), a screening instrument to signal a need for additional care resulting from reduced vision-related quality of life in patients with chronic ophthalmic diseases. The aim of the present study was to evaluate psychometric properties. Methods: A Dutch population-based sample of 2032 participants (mean age, 55 ± 19 years) completed the VQL-6 and other questionnaires on vision-related quality of life, executive functioning, attention, mental health, and symptom validity. In addition, we recruited a sample of 208 ophthalmic patients (mean age, 72 ± 12 years) and 98 age and gender similar controls (mean age, 69 ± 11 years) who completed the VQL-6 and the National Eye Institute Visual Function Questionnaire-25. We studied the factor structure, internal consistency, convergent and divergent validity, and known-groups validity. Results: For the factor analyses, the population-based sample was split randomly in two subsamples. Exploratory factor analysis on the first subsample suggested a two-factor model (visual limitations and general health and quality of life), which was supported by confirmatory factor analyses on the second subsample, and on the patients. The VQL-6 demonstrated good internal consistency within each factor (0.78-0.89), sufficient convergent (r2= 55%) and divergent validity (r2 = 11%-24%), and good known-groups validity (Cohen's r = 0.57; P < 0.001). Conclusions: The VQL-6 has a robust two-factor structure and seems to be a valid tool to assess vision-related quality of life. Additional validation is needed in patients with chronic ophthalmic diseases. Translational Relevance: Future research is needed to determine if the VQL-6 can be used to identify patients with chronic ophthalmic diseases who are in need of additional care.

Effect of Nonoverlapping Visual Field Defects on Vision-related Quality of Life in Glaucoma.

PURPOSE: Glaucoma patients may be considered to have normal vision as long as each point of visual space is perceived by at least 1 eye, that is, with an intact binocular visual field (VF). We aimed to investigate the effect of nonoverlapping VF defects on vision-related quality of life (VR-QoL) in glaucoma. METHODS: We evaluated VR-QoL of glaucoma patients (n = 269) and controls (n = 113) using 4 different questionnaires (National Eye Institute visual function questionnaire [NEI-VFQ-25], NEI-VFQ neuro-ophthalmology supplement, Glaucoma Quality of Life-15, and a luminance-specific questionnaire). We defined "differential VF" (DVF) as a measure of location-specific differences in the VFs of both eyes. Within the group of glaucoma patients, we analyzed the relationship between different aspects of VR-QoL and DVF using ordinal multiple regression analysis. Analyses were adjusted for age, sex, integrated VF (IVF; an estimate of the binocular VF from the monocular VFs), and higher visual acuity of both eyes, and corrected for multiple hypothesis testing. RESULTS: Glaucoma patients had lower VR-QoL than controls. Among the glaucoma patients, DVF was significantly associated with general vision (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.54-0.89), peripheral vision (OR, 0.68; 95% CI, 0.54-0.86), walking on uneven ground (OR, 0.73; 95% CI, 0.58-0.93), crossing the street (OR, 0.61; 95% CI, 0.46-0.83), seeing other road users coming from the side (OR, 0.67; 95% CI, 0.52-0.85), cycling during the day (OR, 0.64; 95% CI, 0.46-0.89) and seeing outside on a sunny day (OR, 0.73; 95% CI, 0.57-0.94). In general, IVF was a stronger predictor of VR-QoL than DVF. CONCLUSIONS: Nonoverlapping VF defects affect VR-QoL. Although IVF is strongly associated with VR-QoL, basing clinical decisions only on IVF leads to overlooking vision problems that patients may have. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Novel ancestry-specific primary open-angle glaucoma loci and shared biology with vascular mechanisms and cell proliferation.

Primary open-angle glaucoma (POAG), a leading cause of irreversible blindness globally, shows disparity in prevalence and manifestations across ancestries. We perform meta-analysis across 15 biobanks (of the Global Biobank Meta-analysis Initiative) (n = 1,487,441: cases = 26,848) and merge with previous multi-ancestry studies, with the combined dataset representing the largest and most diverse POAG study to date (n = 1,478,037: cases = 46,325) and identify 17 novel significant loci, 5 of which were ancestry specific. Gene-enrichment and transcriptome-wide association analyses implicate vascular and cancer genes, a fifth of which are primary ciliary related. We perform an extensive statistical analysis of SIX6 and CDKN2B-AS1 loci in human GTEx data and across large electronic health records showing interaction between SIX6 gene and causal variants in the chr9p21.3 locus, with expression effect on CDKN2A/B. Our results suggest that some POAG risk variants may be ancestry specific, sex specific, or both, and support the contribution of genes involved in programmed cell death in POAG pathogenesis.

Childhood cerebral visual impairment subtype classification based on an extensive versus a limited test battery.

Purpose: 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. Methods: 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. Results: 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 (p < 0.05). The subtle characteristics subtype (extensive n = 19, limited n = 15) showed near normal lower and higher-level visual functions in both test batteries. The higher-level visual function deficits subtype (extensive n = 18, limited n = 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 n = 4, limited n = 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 n = 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. Conclusion: 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.

Greater adherence to a mediterranean diet is associated with lower C-reactive protein (CRP) levels, but not to lower odds of having dry eye disease.

PURPOSE: To investigate the hypothesis that a Mediterranean diet is associated with a lower risk of having dry eye disease (DED) in the general population. METHODS: DED was assessed using the Women's Health Study (WHS) dry eye questionnaire in 58,993 participants from the Dutch Lifelines Cohort with complete available dietary data (20-94 years, 60% female). Level of adherence to a traditional Mediterranean diet was assessed using the modified Mediterranean Diet Score (mMDS). High-sensitivity C-reactive Protein (hsCRP) was included as a marker of whole-body inflammation. Logistic regressions were used to examine the relationship between WHS-defined DED and mMDS, corrected for age, sex, BMI, education, income, and 48 potentially confounding comorbidities. The association between mMDS and hsCRP, and hsCRP and DED, was further explored in separate regressions. RESULTS: Of all participants, 9.1% had DED. In contrast to the hypothesis, higher mMDS levels were associated with greater odds of DED, corrected for demographics, smoking status, BMI, and comorbidities (OR 1.034, 95%CI: 1.015 to 1.055, P = 0.001). Moreover, there was a highly significant relationship between increasing mMDS and lower circulating hsCRP levels; however, there was no significant relationship between hsCRP and DED. CONCLUSIONS: Stronger adherence to a Mediterranean diet does not appear to be associated with lower odds of having DED in the general population. Furthermore, there was no association between hsCRP and DED in this study. However, the previously described link between a Mediterranean diet and lower hsCRP was confirmed in this large population-based study.

Retinal Vessel Caliber Measurement Bias in Fundus Images in the Presence of the Central Light Reflex.

Purpose: To investigate the agreement between a fundus camera and a scanning laser ophthalmoscope in retinal vessel caliber measurements and to identify whether the presence of the central light reflex (CLR) explains potential discrepancies. Methods: For this cross-sectional study, we obtained fundus camera and scanning laser ophthalmoscope images from 85 eyes of 85 healthy individuals (aged 50-65 years) with different blood pressure status. We measured the central retinal artery equivalent (CRAE) and central retinal artery vein equivalent (CRVE) with the Knudtson-Parr-Hubbard algorithm and assessed the CLR using a semiautomatic grading method. We used Bland-Altman plots, 95% limits of agreement, and the two-way mixed effects intraclass correlation coefficient for consistency [ICC(3,1)] to describe interdevice agreement. We used multivariable regression to identify factors associated with differences in between-device measurements. Results: The between-device difference in CRAE (9.5  µm; 95% confidence interval, 8.0-11.1  µm) was larger than the between-device difference in CRVE (2.9  µm; 95% confidence interval, 1.3-4.5  µm), with the fundus camera yielding higher measurements (both P < 0.001). The 95% fundus camera-scanning laser ophthalmoscope limits of agreement were -4.8 to 23.9  µm for CRAE and -12.0 to 17.8  µm for CRVE. The corresponding ICCs(3,1) were 0.89 (95% confidence interval, 0.83-0.92) and 0.91 (95% confidence interval, 0.86-0.94). The between-device CRAE difference was positively associated with the presence of a CLR (P = 0.002). Conclusions: Fundus cameras and scanning laser ophthalmoscopes yield correlated but not interchangeable caliber measurements. The CLR induces bias in arteriolar caliber in fundus camera images, compared with scanning laser ophthalmoscope images. Translational Relevance: Refined measurements could yield better estimates of the association between retinal vessel caliber and ophthalmic or systemic disease.

Association of Systemic Medication Use with Glaucoma and Intraocular Pressure: The European Eye Epidemiology Consortium.

PURPOSE: To investigate the association of commonly used systemic medications with glaucoma and intraocular pressure (IOP) in the European population. DESIGN: Meta-analysis of 11 population-based cohort studies of the European Eye Epidemiology Consortium. PARTICIPANTS: The glaucoma analyses included 143 240 participants and the IOP analyses included 47 177 participants. METHODS: We examined associations of 4 categories of systemic medications-antihypertensive medications (ß-blockers, diuretics, calcium channel blockers [CCBs], α-agonists, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers), lipid-lowering medications, antidepressants, and antidiabetic medications-with glaucoma prevalence and IOP. Glaucoma ascertainment and IOP measurement method were according to individual study protocols. Results of multivariable regression analyses of each study were pooled using random effects meta-analyses. Associations with antidiabetic medications were examined in participants with diabetes 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], 1.23; 95% confidence interval [CI], 1.08 to 1.39). This association was stronger for monotherapy of CCBs with direct cardiac effects (OR, 1.96; 95% CI, 1.23 to 3.12). No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with glaucoma. Use of systemic ß-blockers was associated with a lower IOP (ß coefficient, -0.33 mmHg; 95% CI, -0.57 to -0.08 mmHg). Monotherapy of both selective systemic ß-blockers (ß coefficient, -0.45 mmHg; 95% CI -0.74 to -0.16 mmHg) and nonselective systemic ß-blockers (ß coefficient, -0.54 mmHg; 95% CI, -0.94 to -0.15 mmHg) was associated with lower IOP. A suggestive association was found between use of high-ceiling diuretics and lower IOP (ß coefficient, -0.30 mmHg; 95% CI, -0.47 to -0.14 mmHg) but not when used as monotherapy. No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were 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 ß-blocker use. Both findings potentially are important, given that patients with glaucoma frequently use systemic antihypertensive medications. Determining causality of the CCB association should be a research priority. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Effect of Correcting Peripheral Refractive Errors on Retinal Sensitivity in Younger and Older Healthy Adults.

SIGNIFICANCE: Retinal sensitivity decreases with age and age-related eye diseases. Peripheral retinal sensitivity may also be compromised if the refractive correction is not optimized for peripheral vision. PURPOSE: This study aimed to determine the impact of using a peripheral refractive correction on perimetric thresholds and the influence of age and spherical equivalent on this impact. METHODS: We measured, in 10 younger (20 to 30 years) and 10 older (58 to 72 years) healthy subjects, perimetric thresholds for Goldmann size III stimulus in several test locations along the horizontal meridian of the visual field (eccentricity, 0, ±10, and ±25°), with default central refractive correction and with peripheral refractive corrections as measured with a Hartmann-Shack wavefront sensor. We used analysis of variance to determine the effect of age and spherical equivalent (between-subject variables) and eccentricity and correction method (central vs. eccentricity specific; within-subject variables) on retinal sensitivity. RESULTS: Retinal sensitivity was higher if the eyes were optimally corrected for the concerning test location (P = .008), and the effect of this peripheral correction differed between the younger and older subjects (interaction term between group and correction method: P = .02), primarily because of more myopia in the younger group (P = .003). The average improvement by applying peripheral corrections was 1.4 dB in the older subjects and 0.3 dB in the younger subjects. CONCLUSIONS: Peripheral optical correction has a variable impact on retinal sensitivity, and therefore, assessment of retinal sensitivity may be more accurate if peripheral defocus and astigmatism are corrected.

Goniotomy for Non-Infectious Uveitic Glaucoma in Children.

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.

Factors Associated With Glaucoma Surgery in Pediatric Non-Infectious Uveitis.

PURPOSE: To identify factors associated with glaucoma surgery in pediatric uveitis. METHODS: Patients diagnosed with uveitis before their 18th birthday and with an observation period of at least one year were included in a retrospective case-control study. RESULTS: A total of 185 patients were included, 84 of whom had undergone glaucoma surgery. Juvenile idiopathic arthritis (JIA)-related uveitis was associated with undergoing glaucoma surgery (p = .002). In the JIA-subgroup, the presence of anterior segment complications (OR 3.1 (95% CI 1.0 to 9.6); P = .045) and an IOP > 21 mmHg during the first uveitis remission (OR 4.5 (95% CI 1.3 to 15.2); P = .015) were associated with an increased risk of glaucoma surgery. Sixty-eight percent of the cases needed glaucoma surgery within one year after they started IOP-lowering triple therapy. CONCLUSION: The risk profile for undergoing glaucoma surgery as outlined in this study is a valuable help to recognize and treat secondary glaucoma in a timely manner.

Influence of signal-to-noise ratio, glaucoma stage and segmentation algorithm on OCT usability for quantifying layer thicknesses in the peripapillary retina.

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.

The relationship between habitual water intake and dry eye disease.

PURPOSE: The purpose of this study is to test the hypothesis that greater habitual water intake is associated with lower risk of dry eye disease (DED). METHODS: We included 51 551 participants from the population-based Lifelines cohort (mean age = 51.2 years) in this cross-sectional association study. DED was assessed using the Women's Health Study (WHS) dry eye questionnaire. Water intake was calculated from food frequency questionnaires. Logistic regressions were used to analyse the relationship between DED and water intake or 24-h urine volume, corrected for age, sex, body mass index, physical activity, smoking status, education, income, 48 comorbidities, and 15 medication groups. The main outcome measure was WHS-defined DED. Highly symptomatic dry eye and clinical diagnosis of DED were secondary outcomes. RESULTS: In total, 9.1% of the population had WHS-defined DED. Higher water intake was associated with increased prevalence of WHS-defined DED (OR: 1.011 per 100 ml/day, 95% CI: 1.004-1.017, p = 0.003). After excluding those with a clinical diagnosis, greater water intake was still tied to increased risk of having DED symptoms (OR: 1.010 per 100 ml/day, 95% CI: 1.006-1.015, p < 0.001). Higher 24-h urine volumes were also associated with higher risk of WHS-defined DED (OR: 1.010 per 100 ml/day, 95% CI: 1.005-1.015, p < 0.001). CONCLUSIONS: In this large, population-based study, higher water intake was not tied to reduced risk of DED. Rather, it was associated with a modest increased risk of DED. Interventional studies are needed to fully understand the effect of water intake on DED, but this study found no evidence that greater water intake is beneficial for DED.

Development and validation of a questionnaire-based myopia proxy in adults: the LifeLines Cohort Study.

AIMS: To 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. METHODS: Data 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 <-0.5 D) as a dependent variable and the principal components (PCs) as independent variables. We identified specificity, sensitivity and the classification threshold. Third, the classification equation was applied to the remaining LifeLines participants. The value of the proxy was then explored by calculating its association with educational attainment and a PRS of myopia. RESULTS: A 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. CONCLUSION: Self-administered refractive error-related questions could be used as an effective tool to capture proxy-inferred myopic cases in a population-based setting.

The Relationship Between Caffeine Intake and Dry Eye Disease.

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.

Co-occurrence of chronic kidney disease and glaucoma: Epidemiology and etiological mechanisms.

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.

Uveitic glaucoma in children: a systematic review on surgical outcomes.

PURPOSE: To compare the outcomes and complications of different surgical interventions for secondary glaucoma in pediatric uveitis. METHODS: Systematic review following the PRISMA standards. Main inclusion criteria were surgery for secondary glaucoma in pediatric uveitis at a mean age of 16 years or below, a mean follow-up period of at least 1 year after surgery, and at least 10 eyes per surgical intervention per study. We used the GRADE approach to assess study quality. Primary outcomes were intraocular pressure (IOP) and number of IOP lowering medications before and after surgery. Secondary outcomes were success rate and complications. RESULTS: Fourteen studies fulfilled the inclusion criteria, in which one (n = 11) or more (n = 3) surgical interventions were described, comprising in total six different procedures. According to the GRADE criteria, the quality of the studies was low to very low, in particular because of the small size and the applied study designs. All surgical interventions provided a significant decrease in IOP and number of IOP lowering medications. The success rates during follow-up varied widely, with the lowest rates of success after cyclophotocoagulation. The most frequently reported complications were ocular hypertension, hypotony, and hyphema, with an indication for a reoperation in more than one-third of the cases. Permanent vision loss was infrequently seen and was attributed to prolonged hypotony. CONCLUSIONS: The described surgical interventions are able to prevent blindness by lowering a medically uncontrolled IOP to an acceptable level. Therefore, there is a crucial role for surgical intervention in these children. Based on the present studies, no preferences can be made. Given the reported complications, more research with larger sample sizes and direct comparisons is needed to determine the most successful glaucoma treatment in children with uveitis.