Early detection and treatment of glaucoma can delay vision loss. In this study, we evaluate the performance of handheld chromatic pupillometry (HCP) for the objective and rapid detection of ...functional loss in glaucoma.
In this clinic-based, prospective study, we enrolled 149 patients (median (IQR) years: 68.5 (13.6) years) with confirmed glaucoma and 173 healthy controls (55.2 (26.7) years). Changes in pupil size in response to 9 s of exponentially increasing blue (469 nm) and red (640 nm) light-stimuli were assessed monocularly using a custom-built handheld pupillometer. Pupillometric features were extracted from individual traces and compared between groups. Features with the highest classification potential, selected using a gradient boosting machine technique, were incorporated into a generalised linear model for glaucoma classification. Receiver operating characteristic curve analyses (ROC) were used to compare the performance of HCP, optical coherence tomography (OCT) and Humphrey Visual Field (HVF).
Pupillary light responses were altered in glaucoma compared with controls. For glaucoma classification, HCP yielded an area under the ROC curve (AUC) of 0.94 (95% CI 0.91 to 0.96), a sensitivity of 87.9% and specificity of 88.4%. The classification performance of HCP in early-moderate glaucoma (visual field mean deviation (VFMD) > -12 dB; AUC=0.91 (95% CI 0.87 to 0.95)) was similar to HVF (AUC=0.91) and reduced compared with OCT (AUC=0.97; p=0.01). For severe glaucoma (VFMD ≤ -12 dB), HCP had an excellent classification performance (AUC=0.98, 95% CI 0.97 to 1) that was similar to HVF and OCT.
HCP allows for an accurate, objective and rapid detection of functional loss in glaucomatous eyes of different severities.
We combined finite element (FE) analysis and dynamic magnetic resonance imaging (MRI) to estimate optic nerve head (ONH) strains during horizontal eye movements, and identified factors influencing ...such strains. We also compared ONH strains (prelamina, lamina cribrosa, and retrolamina strains) induced by eye movements to those induced by IOP.
The ocular globes and orbits of a healthy subject were visualized during horizontal eye movements (up to 13°), using dynamic MRI. A baseline FE model of one eye was reconstructed in the primary gaze position, including details from the orbital and ONH tissues. Finite element-derived ONH strains induced by eye movements were compared to those resulting from an IOP of 50 mm Hg. Finally, a FE sensitivity study was performed, in which we varied the stiffness of all ONH connective tissues, to understand their influence on ONH strains.
Our models predicted that, during horizontal eye movements, the optic nerve pulled the ONH posteriorly. Optic nerve head strains following a lateral eye movement of 13° were large and higher than those resulting from an IOP of 50 mm Hg. These results held true even with variations in connective tissue stiffness. We also found that stiff sclerae reduced lamina cribrosa and prelamina strains during eye movements, but stiff optic nerve sheaths significantly increased those strains.
Our models predicted high ONH strains during eye movements, which were aggravated with stiffer optic nerve sheaths. Further studies are needed to explore links between ONH strains induced by eye movements and axonal loss in glaucoma.
Abstract
Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide for which 15 disease-associated loci had been discovered. Among them, only 5 loci have been ...associated with POAG in Asians. We carried out a genome-wide association study and a replication study that included a total of 7378 POAG cases and 36 385 controls from a Japanese population. After combining the genome-wide association study and the two replication sets, we identified 11 POAG-associated loci, including 4 known (CDKN2B-AS1, ABCA1, SIX6 and AFAP1) and 7 novel loci (FNDC3B, ANKRD55-MAP3K1, LMX1B, LHPP, HMGA2, MEIS2 and LOXL1) at a genome-wide significance level (P < 5.0×10−8), bringing the total number of POAG-susceptibility loci to 22. The 7 novel variants were subsequently evaluated in a multiethnic population comprising non-Japanese East Asians (1008 cases, 591 controls), Europeans (5008 cases, 35 472 controls) and Africans (2341 cases, 2037 controls). The candidate genes located within the new loci were related to ocular development (LMX1B, HMGA2 and MAP3K1) and glaucoma-related phenotypes (FNDC3B, LMX1B and LOXL1). Pathway analysis suggested epidermal growth factor receptor signaling might be involved in POAG pathogenesis. Genetic correlation analysis revealed the relationships between POAG and systemic diseases, including type 2 diabetes and cardiovascular diseases. These results improve our understanding of the genetic factors that affect the risk of developing POAG and provide new insight into the genetic architecture of POAG in Asians.
To measure lamina cribrosa (LC) strains (deformations) following abduction and adduction in healthy subjects and to compare them with those resulting from a relatively high acute intraocular pressure ...(IOP) elevation.
A total of 16 eyes from 8 healthy subjects were included. Among the 16 eyes, 11 had peripapillary atrophy (PPA). For each subject, both optic nerve heads (ONHs) were imaged using optical coherence tomography (OCT) at baseline (twice), in different gaze positions (adduction and abduction of 20°) and following an acute IOP elevation of approximately 20 mm Hg from baseline (via ophthalmodynamometry). Strains of LC for all loading scenarios were mapped using a three-dimensional tracking algorithm.
In all 16 eyes, LC strains induced by adduction and abduction were 5.83% ± 3.78% and 3.93% ± 2.57%, respectively, and both significantly higher than the control strains measured from the repeated baseline acquisitions (P < 0.01). Strains of LC in adduction were on average higher than those in abduction, but the difference was not statistically significant (P = 0.07). Strains of LC induced by IOP elevations (on average 21.13 ± 7.61 mm Hg) were 6.41% ± 3.21% and significantly higher than the control strains (P < 0.0005). Gaze-induced LC strains in the PPA group were on average larger than those in the non-PPA group; however, the relationship was not statistically significant.
Our results confirm that horizontal eye movements generate significant ONH strains, which is consistent with our previous estimations using finite element analysis. Further studies are needed to explore a possible link between ONH strains induced by eye movements and axonal loss in optic neuropathies.
This article aims to review the published literature pertaining to the use of anterior segment optical coherence tomography (AS‐OCT) in the evaluation of angle‐closure disease. Searches on the ...available published literature were last conducted on 15 June 2017. Rated as Level I evidence, we found that AS‐OCT has shown good sensitivity and moderate diagnostic accuracy to detect narrow angles when compared with gonioscopy. AS‐OCT quantitative and qualitative parameters demonstrated strong association with the presence of gonioscopically closed angles. This technology provides an objective non‐contact method of assessing the angle that is well tolerated by the patient and correlates well with the information provided by gonioscopy.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
To investigate the association of lens parameters-specifically, lens vault (LV), lens thickness (LT), and lens position (LP)-with angle closure.
Prospective, comparative study.
One hundred two ...Chinese subjects with angle closure (consisting of primary angle closure, primary angle-closure glaucoma, and previous acute primary angle closure) attending a glaucoma clinic and 176 normal Chinese subjects with open angles and no evidence of glaucoma recruited from an ongoing population-based cross-sectional study.
All participants underwent gonioscopy and anterior-segment optical coherence tomography (AS OCT; Carl Zeiss Meditec, Dublin, CA). Customized software was used to measure LV, defined as the perpendicular distance between the anterior pole of the crystalline lens and the horizontal line joining the 2 scleral spurs, on horizontal AS OCT scans. A-scan biometry (US-800; Nidek Co, Ltd, Tokyo, Japan) was used to measures LT and to calculate LP (defined as anterior chamber depth ACD +1/2 LT) and relative LP (RLP; defined as LP/axial length AL).
Lens parameters and angle closure.
Significant differences between angle-closure and normal eyes were found for LV (901±265 vs. 316±272 μm; P<0.001), LT (4.20±0.92 vs. 3.90±0.73 mm; P = 0.01), LT-to-AL ratio (0.18±0.04 vs. 0.16±0.03; P<0.001), ACD (2.66±0.37 vs. 2.95±0.37 mm; P<0.001), and AL (22.86±0.93 vs. 23.92±1.37 mm; P<0.001), but no significant differences were found for LP (4.76±0.51 vs. 4.90±0.54 mm; P = 0.34) or RLP (0.21±0.02 vs. 0.20±0.02; P = 0.14). After adjusting for age, gender, ACD, LT, and RLP, increased LV was associated significantly with angle closure (odds ratio OR, 48.1; 95% confidence interval CI, 12.8-181.3, comparing lowest to highest quartile), but no association was found for LT (OR, 1.78; 95% CI, 0.76-4.16), LP (OR, 1.94; 95% CI, 0.59-6.31), or RLP (OR, 2.08; 95% CI, 0.66-6.57). There was low correlation between LV and LT (Pearson's correlation coefficient PCC, 0.17), between LV and RLP (PCC, 0.08), or between LV and LP (PCC, 0.2).
Eyes with angle closure have thicker lenses with greater LV compared with normal eyes. The LV, which represents the anterior portion of the lens, is a novel parameter independently associated with angle closure after adjusting for age, gender, ACD, and LT.
Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and ...29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.
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IJS, NUK, SBMB, UL, UM, UPUK
To determine the distribution, variation, and determinants of ganglion cell-inner plexiform layer (GC-IPL) thickness in nonglaucomatous eyes measured by high-definition optical coherence tomography ...(HD-OCT).
Six hundred twenty-three Chinese adults aged 40 to 80 years were consecutively recruited from a population-based study. All subjects underwent a standardized interview, ophthalmic examination, and automated perimetry. HD-OCT with macular cube protocol was used to measure the GC-IPL thickness. Univariate and multiple linear regression analyses were performed to examine the relationship between GC-IPL thickness with ocular and systemic factors.
The mean (±SD) age of study subjects was 52.84 ± 6.14 years, 50.1% were male, and all subjects had normal visual fields with no signs of glaucoma or glaucoma suspect. The mean overall, minimum, superior, and inferior GC-IPL thicknesses were 82.78 ± 7.01 μm, 79.67 ± 9.17 μm, 83.30 ± 7.89 μm, and 80.16 ± 8.31 μm, respectively. In multiple linear regression analysis, GC-IPL thickness was significantly associated with age (β = -0.202, P < 0.001), female sex (β = -2.367, P < 0.001), axial length (β = -1.279, P = 0.002), and mean peripapillary retinal nerve fiber layer (RNFL) thickness (β = 0.337, P < 0.001). IOP, central corneal thickness, disc area, serum glucose level, and history of diabetes mellitus had no significant influence on GC-IPL thickness.
Thinner GC-IPL was independently associated with older age, female sex, longer axial length, and thinner RNFL thickness. These factors should be taken into account when interpreting GC-IPL thickness measurements with HD-OCT for glaucoma assessment.
Purpose To objectively quantify choroidal thickness and choroidal volume using fully automated choroidal segmentation software applied to images obtained from enhanced depth imaging spectral-domain ...optical coherence tomography (EDI SD OCT) in a population-based study; and evaluate the ocular and systemic determinants of choroidal thickness and choroidal volume. Design Prospective cross-sectional study. Methods Participants ranging in age from 45 to 85 years were recruited from the Singapore Malay Eye Study-2 (SiMES-2), a follow-up population-based study. All participants (n = 540) underwent a detailed ophthalmic examination, including EDI SD OCT for measurements of thickness and volume of the choroid. Results The intrasession repeatability of choroidal thickness at 5 measured horizontal locations and macular choroidal volume using automated choroidal segmentation software was excellent (intraclass correlation coefficient, 0.97-0.99). Choroid was significantly thicker under the fovea (242.28 ± 97.58 μm), followed by 3 mm temporal (207.65 ± 80.98 μm), and was thinnest at 3 mm nasal (142.44 ± 79.19 μm) location. The mean choroidal volume at central macular region (within a circle of 1 mm diameter) was 0.185 ± 0.69 mm3 . Among the range of ocular and systemic factors studied, age, sex, and axial length were the only significant predictors of choroidal thickness and choroidal volume (all P < .05). Conclusions Using a new automated choroidal segmentation software, we provide fast, reliable, and objective measurements of choroidal thickness and volume in a population-based sample. Male sex, younger age, and shorter axial length are the factors independently associated with thicker choroid and larger choroidal volume. These factors should be taken into consideration when interpreting EDI SD OCT–based choroidal thickness measurements in clinics.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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