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.

Genome-wide CNV investigation suggests a role for cadherin, Wnt, and p53 pathways in primary open-angle glaucoma.

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.

Genetic pre-screening for glaucoma in population-based epidemiology: protocol for a double-blind prospective screening study within Lifelines (EyeLife).

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.

Microcirculatory model predicts blood flow and autoregulation range in the human retina: in vivo investigation with laser speckle flowgraphy.

In this study, we mathematically predict retinal vascular resistance (RVR) and retinal blood flow (RBF), we test predictions using laser speckle flowgraphy (LSFG), we estimate the range of vascular autoregulation, and we examine the relationship of RBF with the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC). Fundus, optical coherence tomography (OCT), and OCT-angiography images, systolic/diastolic blood pressure (SBP/DBP), and intraocular pressure (IOP) measurements were obtained from 36 human subjects. We modeled two circulation markers (RVR and RBF) and estimated individualized lower/higher autoregulation limits (LARL/HARL), using retinal vessel calibers, fractal dimension, perfusion pressure, and population-based hematocrit values. Quantitative LSFG waveforms were extracted from vessels of the same eyes, before and during IOP elevation. LSFG metrics explained most variance in RVR (R2 = 0.77/P = 6.9·10-9) and RBF (R2 = 0.65/P = 1.0·10-6), suggesting that the markers strongly reflect blood flow physiology. Higher RBF was associated with thicker RNFL (P = 4.0·10-4) and GCC (P = 0.003), thus also verifying agreement with structural measurements. LARL was at SBP/DBP of 105/65 mmHg for the average subject without arterial hypertension and at 115/75 mmHg for the average hypertensive subject. Moreover, during IOP elevation, changes in RBF were more pronounced than changes in RVR. These observations physiologically imply that healthy subjects are already close to LARL, thus prone to hypoperfusion. In conclusion, we modeled two clinical markers and described a novel method to predict individualized autoregulation limits. These findings could improve understanding of retinal perfusion and pave the way for personalized intervention decisions, when treating patients with coexisting ophthalmic and cardiovascular pathologies.NEW & NOTEWORTHY We describe and test a new approach to quantify retinal blood flow, based on standard clinical examinations and imaging techniques, linked together with a physiological model. We use these findings to generate individualized estimates of the autoregulation range. We provide evidence that healthy subjects are closer to the lower autoregulation limit than thought before. This suggests that some retinas are less prepared to withstand hypoperfusion, even after small intraocular pressure rises or blood pressure drops.

Study protocol of the DUtch PARkinson Cohort (DUPARC): a prospective, observational study of de novo Parkinson's disease patients for the identification and validation of biomarkers for Parkinson's disease subtypes, progression and pathophysiology.

BACKGROUND: Parkinson's Disease (PD) is a heterogeneous, progressive neurodegenerative disorder which is characterized by a variety of motor and non-motor symptoms. To date, no disease modifying treatment for PD exists. Here, the study protocol of the Dutch Parkinson Cohort (DUPARC) is described. DUPARC is a longitudinal cohort study aimed at deeply phenotyping de novo PD patients who are treatment-naïve at baseline, to discover and validate biomarkers for PD progression, subtypes and pathophysiology. METHODS/DESIGN: DUPARC is a prospective cohort study in which 150 de novo PD subjects will be recruited through a collaborative network of PD treating neurologists in the northern part of the Netherlands (Parkinson Platform Northern Netherlands, PPNN). Participants will receive follow-up assessments after 1 year and 3 years, with the intention of an extended follow-up with 3 year intervals. Subjects are extensively characterized to primarily assess objectives within three major domains of PD: cognition, gastrointestinal function and vision. This includes brain magnetic resonance imaging (MRI); brain cholinergic PET-imaging with fluoroethoxybenzovesamicol (FEOBV-PET); brain dopaminergic PET-imaging with fluorodopa (FDOPA-PET); detailed neuropsychological assessments, covering all cognitive domains; gut microbiome composition; intestinal wall permeability; optical coherence tomography (OCT); genotyping; motor and non-motor symptoms; overall clinical status and lifestyle factors, including a dietary assessment; storage of blood and feces for additional analyses of inflammation and metabolic parameters. Since the start of the inclusion, at the end of 2017, over 100 PD subjects with a confirmed dopaminergic deficit on FDOPA-PET have been included. DISCUSSION: DUPARC is the first study to combine data within, but not limited to, the non-motor domains of cognition, gastrointestinal function and vision in PD subjects over time. As a de novo PD cohort, with treatment naïve subjects at baseline, DUPARC provides a unique opportunity for biomarker discovery and validation without the possible confounding influences of dopaminergic medication. TRIAL REGISTRATION: NCT04180865; registered retrospectively, November 28th 2019.

Transscleral cyclophotocoagulation followed by cataract surgery: a novel protocol to treat refractory acute primary angle closure.

BACKGROUND: To introduce a novel protocol to treat refractory acute primary angle closure (APAC): transscleral cyclophotocoagulation (TCP) followed by cataract surgery. METHODS: Thirteen APAC eyes (13 patients) were enrolled in this prospective case series as study group. All patients underwent emergency TCP (20 pulses of 2000 mW during 2000 ms applied to the inferior quadrant) followed by scheduled cataract surgery. They were compared to 13 age- and gender-matched patients treated with emergency phacotrabeculectomy. We recorded intraocular pressure (IOP), best corrected visual acuity (BCVA), and complications, and several ultrasound biomicroscopy (UBM) parameters before and after TCP. RESULTS: In the study group, IOP decreased from 51.5 ± 7.0 mmHg (mean ± standard deviation) before TCP to 16.4 ± 5.4 mmHg 1 day after TCP (P < 0.001). At 6 months, there was no significant difference in IOP between the study group (14.0 ± 3.4 mmHg) and control group (16.7 ± 4.3 mmHg; P = 0.090); IOP lowering medications were used by 0/13 in the study group and 2/13 patients in the control group (P = 0.48). At 6 months, there was no significant difference in BCVA between the study group and the control group (20/25 (20/200 to 20/25) and 20/30 (20/50 to 20/25), respectively; P = 1.0). The UBM parameters anterior chamber depth (P = 0.016), angle-opening distance at 500 µm (P = 0.011), and maximum ciliary body thickness (P < 0.001) increased significantly while the iris-ciliary process distance decreased significantly (P = 0.020) after TCP. CONCLUSIONS: TCP effectively lowers IOP and modifies the anterior chamber morphology in APAC; TCP followed by cataract surgery can be considered an alternative to treat refractory APAC but needs further evaluation. TRIAL REGISTRATION: This project was registered in Chinese Clinical Trial Registry (ChiCTR1800017475) at July, 31, 2018 (http://www.chictr.org.cn/edit.aspx?pid=29629&htm=4).

Retinal nerve fiber bundle trajectories in Chinese myopic eyes: Comparison with a Caucasian based mathematical model.

Previously we developed a mathematical model for describing the retinal nerve fiber bundle (RNFB) trajectories in the human retina. The model was based on Caucasian eyes that were not selected regarding refraction. The aim of this study was to determine the characteristics of the RNFB trajectories in Chinese myopic eyes. We collected high quality red free fundus images from 80 eyes of 80 Chinese myopic subjects (median [interquartile range/range] refraction -3.9 [-6.0 to -2.5/-10 to -1] D). We traced all visible RNFBs (n = 1460) and evaluated their trajectories using the previously published mathematical model. In the superior-temporal region, the RNFB trajectories of the Chinese myopic eyes were similar to that of the Caucasian eyes (86% of trajectories within the 95% central range of the Caucasian model). In the inferior-temporal region, the trajectories of the Chinese low to moderate myopic eyes were also similar to that of the Caucasian eyes (85%); trajectories of the high myopic eyes (spherical equivalent beyond -6.00 D) were clearly less curved (75%). Associations between individual deviations from the model and axial length, retinal vessel course, and optic disc anatomy were studied with multiple linear regression analysis. In the superior-temporal region, the trajectories were associated with retinal vessel course (P = 0.008) and optic disc size (P = 0.016). In the inferior-temporal region, there was a significant association with axial length (P < 0.001), retinal vessel course (P = 0.006), and disc torsion (P = 0.009).

Incidence of glaucomatous visual field loss after two decades of follow-up: the Rotterdam Study.

To determine the incidence of glaucomatous visual field loss (GVFL) two decades after the start of the Rotterdam Study, and to compare known risk factors for open-angle glaucoma (OAG) between different clinical manifestations of OAG. Of 6806 participants aged 55 years and older from the population-based Rotterdam Study, 3939 underwent visual field testing at baseline and at least one follow-up round. The ophthalmic examinations included optic disc assessment and measurements of intraocular pressure (IOP), refractive error, diastolic blood pressure (DBP), and height and weight. The incidence rate of GVFL was calculated. Associations with the risk factors age, gender, baseline IOP, family history, myopia, DBP, and body-mass index [BMI] were assessed using Cox regression, with different clinical manifestations of OAG as outcome measure (glaucomatous optic neuropathy (GON), GVFL, GVFL and GON, GVFL without GON, and GON without GVFL). Median follow-up was 11.1 (IQR 6.8-17.2; range 5.0-20.3) years. The incidence rate of GVFL was 2.9 (95% confidence interval 2.4-3.4) per 1000 person years (140 cases with incident GVFL in one (n = 113) or both (n = 27) eyes). Baseline IOP and age were significantly associated with all OAG outcomes (all p < 0.001); BMI showed a non-significant protective effect in all outcomes (p = 0.01 to p = 0.09). Gender, myopia, and DBP were not associated with any outcome. Our study provides an estimate of the long-term incidence of GVFL in a predominantly white population. The development of GVFL was strongly associated with baseline IOP and age. Risk factor profiles were similar for the different outcomes.

Glaucoma progression detection with frequency doubling technology (FDT) compared to standard automated perimetry (SAP) in the Groningen Longitudinal Glaucoma Study.

PURPOSE: To determine the usefulness of frequency doubling perimetry (FDT) for progression detection in glaucoma, compared to standard automated perimetry (SAP). METHODS: Data were used from 150 eyes of 150 glaucoma patients from the Groningen Longitudinal Glaucoma Study. After baseline, SAP was performed approximately yearly; FDT every other year. First and last visit had to contain both tests. Using linear regression, progression velocities were calculated for SAP (Humphrey Field Analyzer) mean deviation (MD) and FDT MD and the number of test locations with a total deviation probability below p < 0.01 (TD). Progression velocity tertiles were determined and eyes were classified as slowly, intermediately, or fast progressing for both techniques. Comparison between SAP and FDT classifications were made using a Mantel Haenszel chi-square test. Longitudinal signal-to-noise ratios (LSNRs) were calculated, per patient and per technique, defined as progression velocity divided by the standard deviation of the residuals. RESULTS: Mean (SD) follow-up was 6.4 (1.7) years; median (interquartile range [IQR]) baseline SAP MD -6.6 (-14.2 to -3.6) dB. On average 8.2 and 4.5 tests were performed for SAP and FDT, respectively. Median (IQR) MD slope was -0.16 (-0.46 to +0.02) dB/year for SAP and -0.05 (-0.39 to +0.17) dB/year for FDT. Mantel Haenszel chi-squares of SAP MD vs FDT MD and TD were 12.5 (p < 0.001) and 15.8 (p < 0.001), respectively. LSNRs for SAP MD (median -0.17 yr-1 ) were better than those for FDT MD (-0.04 yr-1 ; p = 0.010). CONCLUSIONS: FDT may be a useful technique for monitoring glaucoma progression in patients who cannot perform SAP reliably.

Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology.

Primary open-angle glaucoma is the most common optic neuropathy and an important cause of irreversible blindness worldwide. The optic nerve head or optic disc is divided in two parts: a central cup (without nerve fibers) surrounded by the neuroretinal rim (containing axons of the retinal ganglion cells). The International Glaucoma Genetics Consortium conducted a meta-analysis of genome-wide association studies consisting of 17,248 individuals of European ancestry and 6,841 individuals of Asian ancestry. The outcomes of the genome-wide association studies were disc area and cup area. These specific measurements describe optic nerve morphology in another way than the vertical cup-disc ratio, which is a clinically used measurement, and may shed light on new glaucoma mechanisms. We identified 10 new loci associated with disc area (CDC42BPA, F5, DIRC3, RARB, ABI3BP, DCAF4L2, ELP4, TMTC2, NR2F2, and HORMAD2) and another 10 new loci associated with cup area (DHRS3, TRIB2, EFEMP1, FLNB, FAM101, DDHD1, ASB7, KPNB1, BCAS3, and TRIOBP). The new genes participate in a number of pathways and future work is likely to identify more functions related to the pathogenesis of glaucoma.

Associations with intraocular pressure across Europe: The European Eye Epidemiology (E3) Consortium.

Raised intraocular pressure (IOP) is the most important risk factor for developing glaucoma, the second commonest cause of blindness globally. Understanding associations with IOP and variations in IOP between countries may teach us about mechanisms underlying glaucoma. We examined cross-sectional associations with IOP in 43,500 European adults from 12 cohort studies belonging to the European Eye Epidemiology (E3) consortium. Each study conducted multivariable linear regression with IOP as the outcome variable and results were pooled using random effects meta-analysis. The association of standardized study IOP with latitude was tested using meta-regression. Higher IOP was observed in men (0.18 mmHg; 95 % CI 0.06, 0.31; P = 0.004) and with higher body mass index (0.21 mmHg per 5 kg/m2; 95 % CI 0.14, 0.28; P < 0.001), shorter height (-0.17 mmHg per 10 cm; 95 % CI -0.25, -0.08; P < 0.001), higher systolic blood pressure (0.17 mmHg per 10 mmHg; 95 % CI 0.12, 0.22; P < 0.001) and more myopic refraction (0.06 mmHg per Dioptre; 95 % CI 0.03, 0.09; P < 0.001). An inverted U-shaped trend was observed between age and IOP, with IOP increasing up to the age of 60 and decreasing in participants older than 70 years. We found no significant association between standardized IOP and study location latitude (P = 0.76). Novel findings of our study include the association of lower IOP in taller people and an inverted-U shaped association of IOP with age. We found no evidence of significant variation in IOP across Europe. Despite the limited range of latitude amongst included studies, this finding is in favour of collaborative pooling of data from studies examining environmental and genetic determinants of IOP in Europeans.

From corneal shape to ocular wavefront in eyes with aspheric IOLs: the feasibility of IOL customisation.

PURPOSE: To determine if it is possible to predict the ocular wavefront aberrations of eyes with an aspheric IOL from the corneal shape and other readily available eye characteristics. A reliable prediction is a prerequisite for future IOL customisation. METHODS: Sixty pseudophakic eyes with aspheric IOLs of 60 patients were included. The corneal shape and the ocular wavefront aberrations were measured postoperatively with a Scheimpflug camera and an aberrometer, respectively. The elevation data of the anterior corneal surface were fitted by Zernike polynomials. Linear regression models for the Zernike coefficients describing the ocular wavefront aberrations up till the fourth order were determined, with as independent variables the Zernike coefficients describing the corneal shape, the eye (right/left), IOL power, and axial length. RESULTS: Linear regression equations with an explained variance (adjusted R-square) above 0.50 were found for five Zernike aberration terms: defocus (z(2,0); adjusted R-square 0.90), the astigmatism terms (0.81 for oblique astigmatism [z(2,-2)] and 0.88 for regular astigmatism [z(2,2)]), vertical coma (z(3,-1); 0.52), and spherical aberration (z(4,0); 0.71). CONCLUSION: The defocus, astigmatism, vertical coma, and spherical aberration terms of the ocular wavefront are strongly associated with the corneal shape in pseudophakic eyes and may thus be predicted from the corneal shape and other eye characteristics.

Common genetic determinants of intraocular pressure and primary open-angle glaucoma.

Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands. We replicated our findings in 7,482 participants from 4 additional cohorts from the UK, Australia, Canada, and the Wellcome Trust Case-Control Consortium 2/Blue Mountains Eye Study. IOP was significantly associated with rs11656696, located in GAS7 at 17p13.1 (p=1.4×10(-8)), and with rs7555523, located in TMCO1 at 1q24.1 (p=1.6×10(-8)). In a meta-analysis of 4 case-control studies (total N = 1,432 glaucoma cases), both variants also showed evidence for association with glaucoma (p=2.4×10(-2) for rs11656696 and p=9.1×10(-4) for rs7555523). GAS7 and TMCO1 are highly expressed in the ciliary body and trabecular meshwork as well as in the lamina cribrosa, optic nerve, and retina. Both genes functionally interact with known glaucoma disease genes. These data suggest that we have identified two clinically relevant genes involved in IOP regulation.

Describing the corneal shape after wavefront-optimized photorefractive keratectomy.

PURPOSE: To develop a procedure for describing wavefront-optimized photorefractive keratectomy (PRK) corneas and to characterize PRK-induced changes in shape. METHODS: We analyzed preoperative and postoperative corneal elevation data of 41 eyes of 41 patients (mean [±SD] age, 38 [±11] years) who underwent a myopia-correcting (preoperative spherical equivalent refraction -3.9 [±1.5] diopters) wavefront-optimized PRK, assessed with Scheimpflug imaging. Zernike polynomials were fitted to the elevation data. The diameter of the greatest corneal zone that could be analyzed and the number of Zernike orders needed to make a reliable fit were determined, based on the fitting error. The PRK-induced changes in corneal shape were studied. RESULTS: All subjects could be included for analysis of zones up to 6 mm in diameter. This was 90, 83, and 44% for 7, 8, and 9 mm, respectively. The number of Zernike orders (terms) needed for an accurate fit ranged from four (15) for a 4-mm analyzed zone diameter to eight (45) for 8 mm. For the anterior surface, the spherical aberration term decreased significantly (p < 0.01) after PRK for the 4-mm analyzed zone diameter (-0.09 µm), remained unchanged for 5 mm (+0.01 µm; p = 0.56), and increased significantly for 6 mm (+0.40 µm) and above (p < 0.01). There was no significant change in any other higher-order Zernike term, but the square root of the sum of the squares of all higher-order terms increased significantly for all analyzed zone diameters. Photorefractive keratectomy did not influence the posterior corneal shape. CONCLUSIONS: The cornea after wavefront-optimized PRK can be described as accurately as a healthy cornea and with a similar number of Zernike polynomials. The anterior corneal shape changes significantly after treatment, whereas the posterior corneal shape remains unchanged. The observed effect of wavefront-optimized ablation on the spherical aberration term depends on the diameter of the analyzed zone.

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.

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.

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.