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Purpose: To assess the psychometric properties of glaucoma-specific health-related quality of life (HRQoL) item banks (IBs), and explore their efficiency using computerized adaptive testing (CAT) simulations. Methods: In this cross-sectional, clinical study, 300 Asian glaucoma patients answered 221 items within seven IBs: Ocular Comfort Symptoms (OS); Activity Limitation (AL); Lighting (LT); Mobility (MB); Glaucoma Management (GM); Psychosocial (PSY); and Work (WK). Rasch analysis was conducted to assess each IB's psychometric properties (e.g., item "fit" to the construct; unidimensionality) and a set of analytic performance criteria guiding decision making relating to retaining or dropping domains and items was employed. CAT simulations determined the mean number of items for 'high' and 'moderate' measurement precision (stopping rule: SEM 0.3 and 0.387, respectively). Results: Participants' mean age was 67.2 ± 9.2 years (62% male; 87% Chinese). LT, MB, and GM displayed good psychometric properties overall. To optimize AL's psychometric properties, 16 items were deleted due to poor "fit", high missing data, item bias, low discrimination and/or a low clinical/patient importance rating. To resolve multidimensionality in PSY, we rehomed 16 items into a "Concern (CN)" domain. PSY and CN required further amendment, including collapsing of response categories, and removal of poorly functioning items (N = 7). Due to poor measurement precision, low applicability and high ceiling effect, low test information indices, and low item separation index the WK IB was not considered further. In CAT simulations on the final seven IBs (n = 182 items total), an average of 12.1 and 15.7 items per IB were required for moderate and high precision measurement, respectively. Conclusions: After reengineering our seven IBs, they displayed robust psychometric properties and good efficiency in CAT simulations. Once finalized, GlauCAT™-Asian may enable comprehensive assessment of the HRQoL impact of glaucoma and associated treatments. [ABSTRACT FROM AUTHOR]

Background: A glaucoma-specific health-related quality of life (HRQoL) item bank (IB) and computerized adaptive testing (CAT) system relevant to Asian populations is not currently available. We aimed to develop content for an IB focusing on HRQoL domains important to Asian people with glaucoma; and to compare the content coverage of our new instrument with established glaucoma-specific instruments. Methods: In this qualitative study of glaucoma patients recruited from the Singapore National Eye Centre (November 2018-November 2019), items/domains were generated from: (1) glaucoma-specific questionnaires; (2) published articles; (3) focus groups/semi-structured interviews with glaucoma patients (n = 27); and (4) feedback from glaucoma experts. Data were analyzed using the constant comparative method. Items were systematically refined to a concise set, and pre-tested using cognitive interviews with 27 additional glaucoma patients. Results: Of the 54 patients (mean ± standard deviation [SD] age 66.9 ± 9.8; 53.7% male), 67 (62.0%), 30 (27.8%), and 11 (10.2%) eyes had primary open angle glaucoma, angle closure glaucoma, and no glaucoma respectively. Eighteen (33.3%), 11 (20.4%), 8 (14.8%), 12 (22.2%), and 5 (9.3%) patients had no, mild, moderate, severe, or advanced/end-stage glaucoma (better eye), respectively. Initially, 311 items within nine HRQoL domains were identified: Visual Symptoms, Ocular Comfort Symptoms, Activity Limitation, Driving, Lighting, Mobility, Psychosocial, Glaucoma management, and Work; however, Driving and Visual Symptoms were subsequently removed during the refinement process. During cognitive interviews, 12, 23 and 10 items were added, dropped and modified, respectively. Conclusion: Following a rigorous process, we developed a 221-item, 7-domain Asian glaucoma-specific IB. Once operationalised using CAT, this new instrument will enable precise, rapid, and comprehensive assessment of the HRQoL impact of glaucoma and associated treatment efficacy. [ABSTRACT FROM AUTHOR]

We aimed to verify a custom virtual fields method (VFM) to estimate the patient-specific biomechanical properties of human optic nerve head (ONH) tissues, given their full-field deformations induced by intraocular pressure (IOP). To verify the accuracy of VFM, we first generated 'artificial' ONH displacements from predetermined (known) ONH tissue biomechanical properties using finite element analysis. Using such deformations, if we are able to match back the known biomechanical properties, it would indicate that our VFM technique is accurate. The peripapillary sclera was assumed anisotropic hyperelastic, while all other ONH tissues were considered isotropic. The simulated ONH displacements were fed into the VFM algorithm to extract back the biomechanical properties. The robustness of VFM was also tested against rigid body motions and noise added to the simulated displacements. Then, the computational speed of VFM was compared to that of a gold-standard stiffness measurement method (inverse finite element method or IFEM). Finally, as proof of principle, VFM was applied to IOP-induced ONH deformation data (obtained from one subject's eye imaged with OCT), and the biomechanical properties of the prelamina and lamina cribrosa (LC) were extracted. From given ONH displacements, VFM successfully matched back the biomechanical properties of ONH tissues with high accuracy and efficiency. For all parameters, the percentage errors were less than 0.05%. Our method was insensitive to rigid body motions and was also able to recover the material parameters in the presence of noise. VFM was also found 125 times faster than the gold-standard IFEM. Finally, the estimated shear modulus for the prelamina and the LC of the studied subject's eye were 33.7 and 63.5 kPa, respectively. VFM may be capable of measuring the biomechanical properties of ONH tissues with high speed and accuracy. It has potential in identifying patient-specific ONH biomechanical properties in the clinic if combined with optical coherence tomography. [ABSTRACT FROM AUTHOR]

Purpose: To determine the ocular anatomical factors influencing the pupillary light reactions to different wavelengths of light, measured with chromatic pupillometry. Methods: Community-based, cross-sectional study including subjects with normal ocular health (ages 50-79 years). Direct pupillary responses to continuously increasing irradiances (6.8 to 13.8 log photons cm s) of red (631 nm) and blue (469 nm) light were measured, using a dedicated infrared pupillometer. All subjects underwent swept source optical coherence tomography (SS-OCT, CASIA SS-1000, Tomey Corporation, Nagoya, Japan) and noncontact partial coherence laser interferometry (Lenstar LS900, Haag-Streit AG, Switzerland). Univariate and multivariable regression analyses were performed to determine the anatomical features influencing pupillographic parameters. Results: Among the 177 included subjects, 167 (94.4 %) were Chinese and 116 (65.5 %) female. The average baseline pupil diameter in darkness (β = −0.080, p < 0.001) and the amplitude of the relative pupillary constriction (β = −0.233, p = 0.006) to blue light decreased with age. The amplitude of pupillary constriction was significantly larger in patients with a thinner iris, in response to stimulation with blue (β = −0.321, p < 0.001) and red light (β = −0.336, p < 0.001). Other ocular parameters (i.e., lens vault, anterior chamber depth width, iris volume, iris curvature, and lens thickness) were not significantly associated with pupillometric outcomes. Conclusions: The amplitude of the pupillary light constriction to chromatic photic stimuli is reduced with increasing age and iris thickness in subjects with normal ocular health, a finding which needs to be integrated into future pupillometric studies. [ABSTRACT FROM AUTHOR]

Purpose: To assess variations in the iridocorneal angle width and iris volume in Chinese subjects using swept-source optical coherence tomography (SS-OCT). Methods: Consecutive subjects, aged 40-80 years, with no previous ophthalmic problems were recruited from a population-based study of Chinese Singaporeans. All subjects underwent 360° SS-OCT (SS-1000 CASIA, Tomey Corporation, Nagoya, Japan) angle imaging and gonioscopy in one randomly selected eye in the dark. For each eye, 16 frames (11.25° apart) were selected for analysis from 128 cross-sectional images, and measurements of the trabecular iris space area 750 μm from the scleral spur (TISA750) and iris volume were made for each image. The measurements from four consecutive frames were further averaged as a sector of 45°. Sector-wise angle width and quadrant-wise iris volume were analyzed. Results: Two hundred and twelve subjects (90 with closed-angles) were examined. The majority of the subjects were female (70.7 %) with mean age 61 (±8.9) years. The TISA750 (mm) of superior [0.101 (0.09)], inferior [0.105 (0.09)], superior-nasal [0.111 (0.09)] and superior-temporal [0.117 (0.09)] sectors were smaller compared with other sectors ( P < 0.05). The nasal iris volume (mm) was the smallest compared with other quadrants for the entire cohort [nasal 8.18 (1.2) < inferior 9.13 (1.3) < temporal 9.16 (1.2) < superior 9.33 (1.3), P < 0.001], as well as for open- and closed-angle groups. Conclusions: The irido-corneal angle was narrower in the superior, inferior, superior-nasal and superior-temporal sectors compared with other sectors. Iris volume in the nasal quadrant was the smallest compared with the other quadrants. [ABSTRACT FROM AUTHOR]

Purpose: Measurements of the angle width by ultrasound biomicroscopy or anterior segment optical coherence tomography are usually performed 500 μm from the scleral spur, as the anterior part of trabecular meshwork (TM) is assumed to lie within this distance. The aim of this study was to measure TM width using swept source optical coherence tomography (SS-OCT, CASIA SS-1000, Tomey Corporation, Nagoya, Japan), and to investigate factors influencing this measurement. Methods: Participants underwent gonioscopy and SS-OCT imaging in the dark. High-definition SS-OCT images were corrected for refractive distortion; and customized software (ImageJ; National Institutes of Health, Bethesda, MD, USA) was utilized to measure TM width (distance between the scleral spur and Schwalbe's line). Linear regression analysis was performed to assess the relationship between TM width with demographic and angle parameters. Results: One hundred and forty eight Chinese subjects were analyzed. The majority was female (62.4 %); the mean age was 59.2 ± 8.68 years. Identification of the scleral spur and Schwalbe's line with SS-OCT was possible in 590 (99.7 %) and 585 angle quadrants (98.8 %) respectively. TM width was wider in the inferior and superior quadrants (mean 889 [SD 138] and 793 [136] μm), compared to the nasal and temporal quadrants (712 [137] and 724 [115] μm, P < 0.001). There was a difference in average TM width between open (789 [100]) and closed angle eyes (753 [86]) ( P = 0.048). There was no significant association between TM width and angle parameters, laterality, or demographic factors. Conclusions: In SS-OCT HD images, the mean TM width varied from 710 to 890 μm in the different quadrants of the eye, and the inferior quadrant TM was the widest compared to other quadrants. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the inter- and intra-observer agreement of measurement of the iris-trabecular contact (ITC) index, a measure of the degree of angle closure, using swept source optical coherence tomography (SSOCT, CASIA SS-1000, Tomey Corporation, Nagoya, Japan). Methods: One randomly selected eye of 60 subjects was imaged under dark room conditions. The SSOCT 3-dimensional angle scan simultaneously obtains 128 radial scans of the anterior chamber for the entire circumference of the angle. Post-imaging analysis estimated the ITC index using in-built software. For intra-observer agreement for image grading, one examiner performed the grading twice in a masked fashion and random order after a 1-week interval. A second examiner graded images to assess inter-observer agreement for image grading. For intra-observer agreement for image acquisition, a single operator imaged patients twice. For inter-observer agreement for image acquisition, a single observer graded two sets of images acquired by two different operators on the same patient. Bland-Altman plots and 95 % limits of agreement (LOA) were reported. Results: Study subjects were predominantly Chinese (54/60, 90 %) and female (42/60, 70 %), with a mean age of 65.5 years. The median ITC index for eyes with open angles (31/60) and closed angles was 20 % (95 % confidence interval [CI] - 13.6, 27.8) and 49 % (95%CI - 35.5, 69.2) respectively. The mean difference (95 % LOA) for intra-observer agreement for image grading and image acquisition were −0.8 % (−8.2, 6.5) and 0.6 % (−10.9, 9.7); corresponding inter- observer agreement were 0.1 % (−10, 10.1) and −0.3 % (−11.1, 10.5) respectively. Conclusions: The inter- and intra-observer agreement of the ITC index, as a measure of extent of angle closure using SSOCT, was good. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the speed of pupil constriction (SPC) in response to a standardized change in illumination from dark to light using anterior segment optical coherence tomography (AS-OCT) in eyes with closed angles, compared to those with open angles. Methods: This was a prospective, comparative, observational study. Study subjects with primary angle-closure glaucoma (PACG) and/or primary angle-closure (PAC) were recruited along with a group of normal as controls. Videos of iris and anterior segment changes in response to illumination were captured with real-time video recording from AS-OCT and analysed frame by frame, beginning from a dilated to a constricted pupil. Customized software was used to measure speed of iris constriction, anterior chamber depth (ACD), anterior chamber width (ACW), iris thickness, and pupil diameter (PD). SPC was defined as the rate of pupil diameter change in response to illumination. Results: One hundred and sixty three Chinese subjects were recruited in this study. A total of 137 of 163 eligible videos (82.5%) were available for analysis, comprising 87 subjects with closed angles (all had undergone laser peripheral iridotomies before) and 50 with open angles. SPC was less in eyes with closed angles (1.22 mm/sec vs 1.56 mm/sec, p < 0.001), after adjusting for age and ACW, and was positively correlated with axial length, ACD, anterior chamber angle status, PD in the dark, and iris thickness in the dark, (all r > 0.2, all p < 0.05). In multivariate analysis, SPC was independently associated with anterior chamber angle status (closed angle vs open angle) (β = 0.276, p = 0.016) and PD in dark (β = 0.129, p = 0.009), after adjusting for age, ACW, ACD, iris thickness and vertical cup-to-disc ratio. Conclusions: Compared to those with open angles, eyes with closed angles in Chinese subjects have slower speed of pupil constriction in response to dark-light change, even after adjusting for biometric factors associated with angle closure. The results suggest that differences in irido-pupillary dynamics may play a role in the pathogenesis of angle closure. [ABSTRACT FROM AUTHOR]

Background: Extracellular matrix (ECM) accumulation in the trabecular meshwork tissues of glaucoma patients has been demonstrated as one of the factors that contribute to glaucoma pathology. Transforming growth factor-β (TGFβ) has its fundamental function in regulating the ECM molecules and has been implicated in glaucoma pathology. In this study, the association of the TGFB1 -509C>T single nucleotide polymorphism (SNP) with primary open angle glaucoma (POAG) in patients from India is analyzed. Methods: One-hundred and six POAG patients and 104 controls were selected after comprehensive ophthalmic examinations. TGFB1 alleles were typed by restriction enzyme digestion with the isoschizomer Eco81I of Bsu36I, whose site is altered by the -509C>T SNP, and statistically analyzed for any significant association. Two clinical variables, vertical cup disc ratio (CDR) and intraocular pressure (IOP), were compared at diagnosis by the Mann-Whitney test for any significant association with the polymorphism. Results: Statistical analysis between the two groups did not suggest any significant difference in the distribution of allele and genotype frequencies. The Mann-Whitney test did not show any significant p value for the clinical parameters IOP (p = 0.29 and 0.59) and CDR (p = 0.26 and 0.17). Conclusions: The current study shows that the TGFB1 -509C>T polymorphism might not be associated with POAG. Analysis of the other polymorphisms in the regulatory region of the TGFB1 gene could give a better understanding of the role of TGFβ?in POAG pathogenesis. [ABSTRACT FROM AUTHOR]

This study was designed to evaluate if primary open angle glaucoma (POAG) and its severity are associated with the shape of the lamina cribrosa (LC) as measured by a global shape index (LC-GSI), or other indices of LC curvature or depth. Optical coherence tomography (OCT) scans of the optic nerve head (OHN) were obtained from subjects with POAG (n = 99) and non-glaucomatous controls (n = 76). ONH structures were delineated, the anterior LC morphology reconstructed in 3D, and the LC-GSI calculated (more negative values denote greater posterior concavity). Anterior LC depth and 2D-curvature were also measured. Severity of glaucoma was defined by the extent of visual field loss, based on the Hodapp-Parrish-Anderson grading. Linear regression analyses compared LC characteristics between controls, mild-moderate, and advanced POAG groups. After adjusting for age, gender, ethnicity, intraocular pressure, axial length and corneal curvature, the LC-GSI was most negative in the advanced POAG group (mean [standard error] = −0.34 [0.05]), followed by the mild-moderate POAG group (−0.31 [0.02]) and then controls (−0.23 [0.02], PTrend = 0.01). There was also a significant trend of increasing LC depth and greater LC horizontal curvature with increasing severity of glaucoma (PTrend = 0.04 and 0.02, respectively). Therefore, with more severe glaucoma, the LC-GSI was increasingly more negative, and the anterior LC depth and curvature greater. These observations collectively correspond to greater cupping of the ONH at the level of the LC. As the LC-GSI describes the 3D anterior LC morphology, its potential usage may be complementary to existing ONH parameters measured on OCT. [ABSTRACT FROM AUTHOR]

Chromatic pupillometry is an emerging modality in the assessment of retinal and optic nerve disorders. Herein, we evaluate the effect of low and moderate refractive errors on pupillary responses to blue- and red-light stimuli in a healthy older population. This study included 139 participants (≥50 years) grouped by refractive error: moderate myopes (>−6.0D and ≤−3.0D, n = 24), low myopes (>−3.0D and <−0.5D, n = 30), emmetropes (≥−0.5D and ≤0.5D, n = 31) and hyperopes (>0.5D and <6.0D, n = 54). Participants were exposed to logarithmically ramping-up blue (462 nm) and red (638 nm) light stimuli, designed to sequentially activate rods, cones and intrinsically-photosensitive retinal ganglion cells. Pupil size was assessed monocularly using infra-red pupillography. Baseline pupil diameter correlated inversely with spherical equivalent (R = −0.26, P < 0.01), and positively with axial length (R = 0.37, P < 0.01) and anterior chamber depth (R = 0.43, P < 0.01). Baseline-adjusted pupillary constriction amplitudes to blue light did not differ between groups (P = 0.45), while constriction amplitudes to red light were greater in hyperopes compared to emmetropes (P = 0.04) at moderate to bright light intensities (12.25-14.0 Log photons/cm²/s). Our results demonstrate that low and moderate myopia do not alter pupillary responses to ramping-up blue- and red-light stimuli in healthy older individuals. Conversely, pupillary responses to red light should be interpreted cautiously in hyperopic eyes. [ABSTRACT FROM AUTHOR]