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.
Anterior segment optical coherence tomography (AS-OCT) provides an objective imaging modality for visually identifying anterior segment structures. An automated detection system could assist ...ophthalmologists in interpreting AS-OCT images for the presence of angle closure.
Development of an artificial intelligence automated detection system for the presence of angle closure.
A deep learning system for automated angle-closure detection in AS-OCT images was developed, and this was compared with another automated angle-closure detection system based on quantitative features. A total of 4135 Visante AS-OCT images from 2113 subjects (8270 anterior chamber angle images with 7375 open-angle and 895 angle-closure) were examined. The deep learning angle-closure detection system for a 2-class classification problem was tested by 5-fold cross-validation. The deep learning system and the automated angle-closure detection system based on quantitative features were evaluated against clinicians' grading of AS-OCT images as the reference standard.
The area under the receiver operating characteristic curve of the system using quantitative features was 0.90 (95% confidence interval CI 0.891–0.914) with a sensitivity of 0.79 ± 0.037 and a specificity of 0.87 ± 0.009, while the area under the receiver operating characteristic curve of the deep learning system was 0.96 (95% CI 0.953–0.968) with a sensitivity of 0.90 ± 0.02 and a specificity of 0.92 ± 0.008, against clinicians' grading of AS-OCT images as the reference standard.
The results demonstrate the potential of the deep learning system for angle-closure detection in AS-OCT images.
To evaluate whether a chromatic pupillometry test can be used to detect impaired function of intrinsically photosensitive retinal ganglion cells (ipRGCs) in patients with primary open-angle glaucoma ...(POAG) and to determine if pupillary responses correlate with optic nerve damage and visual loss.
Cross-sectional study.
One hundred sixty-one healthy controls recruited from a community polyclinic (55 men; 151 ethnic Chinese) and 40 POAG patients recruited from a glaucoma clinic (22 men; 35 ethnic Chinese) 50 years of age or older.
Subjects underwent monocular exposure to narrowband blue light (469 nm) or red light (631 nm) using a modified Ganzfeld dome. Each light stimulus was increased gradually over 2 minutes to activate sequentially the rods, cones, and ipRGCs that mediate the pupillary light reflex. Pupil diameter was recorded using an infrared pupillography system.
Pupillary responses to blue light and red light were compared between control subjects and those with POAG by constructing dose-response curves across a wide range of corneal irradiances (7–14 log photons/cm2 per second). In patients with POAG, pupillary responses were evaluated relative to standard automated perimetry testing (Humphrey Visual Field HVF; Carl Zeiss Meditec, Dublin, CA) and scanning laser ophthalmoscopy parameters (Heidelberg Retinal Tomography HRT; Heidelberg Engineering, Heidelberg, Germany).
The pupillary light reflex was reduced in patients with POAG only at higher irradiance levels, corresponding to the range of activation of ipRGCs. Pupillary responses to high-irradiance blue light associated more strongly with disease severity compared with responses to red light, with a significant linear correlation observed between pupil diameter and HVF mean deviation (r = −0.44; P = 0.005) as well as HRT linear cup-to-disc ratio (r = 0.61; P < 0.001) and several other optic nerve head parameters.
In glaucomatous eyes, reduced pupillary responses to high-irradiance blue light were associated with greater visual field loss and optic disc cupping. In POAG, a short chromatic pupillometry test that evaluates the function of ipRGCs can be used to estimate the degree of damage to retinal ganglion cells that mediate image-forming vision. This approach could prove useful in detecting glaucoma.
To compare anterior segment parameters, assessed by anterior segment optical coherence tomography (ASOCT), in subjects categorized as primary angle closure suspect (PACS), primary angle closure ...(PAC), primary angle closure glaucoma (PACG), and previous acute PAC (APAC); and to identify factors associated with APAC.
This was a prospective ASOCT study of 425 subjects with angle closure (176 PACS, 66 PAC, 125 PACG, and 58 APAC). Customized software was used to measure ASOCT parameters, including angle opening distance (AOD750), trabecular-iris space area (TISA750), anterior chamber depth, width, area and volume (ACD, ACW, ACA, ACV), iris thickness (IT750), iris area (IAREA), and lens vault (LV). Mean differences in anterior segment parameters were evaluated by analysis of covariance (ANCOVA) adjusted for age, sex, and pupil diameter (PD).
Comparison among the different subgroups showed that ACD, ACA, and ACV were smallest, and IT750 thickest in the APAC group compared with the other subgroups (P < 0.001). LV was greatest in the APAC group (1218 ± 34 μm) followed by PAC (860 ± 31 μm), PACG (845 ± 23 μm), and PACS (804 ± 19 μm), respectively (P = <0.001). While the APAC group had the narrowest angles, the PACS group had the widest (P < 0.001 for both AOD750 and TISA750). Logistic regression showed that greater LV (P = <0.001), narrower TISA750 (P = <0.001), and thicker IT750 (P = 0.007) were the major determinants of APAC.
Eyes with APAC had the narrowest angles, smallest anterior segment dimensions, thickest iris, and largest LV compared with PACS, PAC, and PACG. LV, TISA750, and IT750 were the major determinants of APAC.
Acute primary angle closure (APAC) is a potentially blinding condition. It is one of the few ophthalmic emergencies and carries high rates of visual morbidity in the absence of timely intervention. ...Laser peripheral iridotomy (LPI) has been the standard of care thus far. However, LPI does not eliminate the long-term risk of chronic angle closure glaucoma and other associated sequelae. There has been increasing interest in lens extraction as the primary treatment for the spectrum of primary angle closure disease, and it is as yet unclear whether these results can be extrapolated to APAC, and whether lens extraction provides better long-term outcomes. We therefore sought to evaluate the effectiveness of lens extraction in APAC to help inform the decision-making process. OBJECTIVES: To assess the effect of lens extraction compared to LPI in the treatment of APAC.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 1), Ovid MEDLINE, Ovid MEDLINE E-pub Ahead of Print, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily (January 1946 to 10 January 2022), Embase (January 1947 to 10 January 2022), PubMed (1946 to 10 January 2022), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to 10 January 2022), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search. We last searched the electronic databases on 10 January 2022.
We included randomized controlled clinical trials comparing lens extraction against LPI in adult participants ( ≥ 35 years) with APAC in one or both eyes.
We used standard Cochrane methodology and assessed the certainty of the body of evidence for prespecified outcomes using the GRADE approach.
We included two studies conducted in Hong Kong and Singapore, comprising 99 eyes (99 participants) of predominantly Chinese origin. The two studies compared LPI with phacoemulsification performed by experienced surgeons. We assessed that both studies were at high risk of bias. There were no studies evaluating other types of lens extraction procedures. Phacoemulsification may result in an increased proportion of participants with intraocular pressure (IOP) control compared with LPI at 18 to 24 months (risk ratio (RR) 1.66, 95% confidence interval (CI) 1.28 to 2.15; 2 studies, n = 97; low certainty evidence) and may reduce the need for further IOP-lowering surgery within 24 months (RR 0.07, 96% CI 0.01 to 0.51; 2 studies, n = 99; very low certainty evidence). Phacoemulsification may result in a lower mean IOP at 12 months compared to LPI (mean difference (MD) -3.20, 95% CI -4.79 to -1.61; 1 study, n = 62; low certainty evidence) and a slightly lower mean number of IOP-lowering medications at 18 months (MD -0.87, 95% CI -1.28 to -0.46; 1 study, n = 60; low certainty evidence), but this may not be clinically significant. Phacoemulsification may have little to no effect on the proportion of participants with one or more recurrent APAC episodes in the same eye (RR 0.32, 95% CI 0.01 to 7.30; 1 study, n = 37; very low certainty evidence). Phacoemulsification may result in a wider iridocorneal angle assessed by Shaffer grading at six months (MD 1.15, 95% CI 0.83 to 1.47; 1 study, n = 62; very low certainty evidence). Phacoemulsification may have little to no effect on logMAR best-corrected visual acuity (BCVA) at six months (MD -0.09, 95% CI -0.20 to 0.02; 2 studies, n = 94; very low certainty evidence). There was no evidence of a difference in the extent of peripheral anterior synechiae (PAS) (clock hours) between intervention arms at 6 months (MD -1.86, 95% CI -7.03 to 3.32; 2 studies, n = 94; very low certainty evidence), although the phacoemulsification group may have less PAS (degrees) at 12 months (MD -94.20, 95% CI -140.37 to -48.03; 1 study, n = 62) and 18 months (MD -127.30, 95% CI -168.91 to -85.69; 1 study, n = 60). In one study, there were 26 adverse events in the phacoemulsification group: intraoperative corneal edema (n = 12), posterior capsular rupture (n = 1), intraoperative bleeding from iris root (n = 1), postoperative fibrinous anterior chamber reaction (n = 7), and visually significant posterior capsular opacification (n = 5), and no cases of suprachoroidal hemorrhage or endophthalmitis. There were four adverse events in the LPI group: closed iridotomy (n = 1) and small iridotomies that required supplementary laser (n = 3). In the other study, there was one adverse event in the phacoemulsification group (IOP > 30 mmHg on day 1 postoperatively (n = 1)), and no intraoperative complications. There were five adverse events in the LPI group: transient hemorrhage (n = 1), corneal burn (n = 1), and repeated LPI because of non-patency (n = 3). Neither study reported health- or vision-related quality of life measures.
Low certainty evidence suggests that early lens extraction may produce more favorable outcomes compared to initial LPI in terms of IOP control. Evidence for other outcomes is less clear. Future high-quality and longer-term studies evaluating the effects of either intervention on the development of glaucomatous damage and visual field changes as well as health-related quality of life measures would be helpful.
To examine the efficacy of laser peripheral iridotomy (LPI) in patients who received a diagnosis of primary angle-closure suspect (PACS).
Prospective, randomized controlled trial.
This multicenter, ...randomized controlled trial (ClinicalTrials.gov identifier, NCT00347178) enrolled 480 patients older than 50 years from glaucoma clinics in Singapore with bilateral asymptomatic PACS (defined as having ≥2 quadrants of appositional angle closure on gonioscopy).
Each participant underwent prophylactic LPI in 1 randomly selected eye, whereas the fellow eye served as a control. Patients were followed up yearly for 5 years.
The primary outcome measure was development of primary angle closure (PAC; defined as presence of peripheral anterior synechiae, intraocular pressure IOP of >21 mmHg, or both or acute angle closure AAC) or primary angle-closure glaucoma (PACG) over 5 years.
Of the 480 randomized participants, most were Chinese (92.7%) and were women (75.8%) with mean age of 62.8 ± 6.9 years. Eyes treated with LPI reached the end point less frequently after 5 years (n = 24 5.0%; incidence rate IR, 11.65 per 1000 eye-years) compared with control eyes (n = 45 9.4%; IR, 21.84 per 1000 eye-years; P = 0.001). The adjusted hazard ratio (HR) for progression to PAC was 0.55 (95% confidence interval CI, 0.37-0.83; P = 0.004) in LPI-treated eyes compared with control eyes. Older participants (per year; HR, 1.06; 95% CI, 1.03-1.10; P < 0.001) and eyes with higher baseline IOP (per millimeter of mercury; HR, 1.35; 95% CI, 1.22-1.50; P < 0.0001) were more likely to reach an end point. The number needed to treat to prevent an end point was 22 (95% CI, 12.8-57.5).
In patients with bilateral asymptomatic PACS, eyes that underwent prophylactic LPI reached significantly fewer end points compared with control eyes over 5 years. However, the overall incidence of PAC or PACG was low.
(1) To use finite element (FE) modelling to estimate local iris stresses (i.e. internal forces) as a result of mechanical pupil expansion; and to (2) compare such stresses as generated from several ...commercially available expanders (Iris hooks, APX dilator and Malyugin ring) to determine which design and deployment method are most likely to cause iris damage.
We used a biofidelic 3-part iris FE model that consisted of the stroma, sphincter and dilator muscles. Our FE model simulated expansion of the pupil from 3 mm to a maximum of 6 mm using the aforementioned pupil expanders, with uniform circular expansion used for baseline comparison. FE-derived stresses, resultant forces and area of final pupil opening were compared across devices for analysis.
Our FE models demonstrated that the APX dilator generated the highest stresses on the sphincter muscles, (max: 6.446 MPa; average: 5.112 MPa), followed by the iris hooks (max: 5.680 MPa; average: 5.219 MPa), and the Malyugin ring (max: 2.144 MPa; average: 1.575 MPa). Uniform expansion generated the lowest stresses (max: 0.435MPa; average: 0.377 MPa). For pupil expansion, the APX dilator required the highest force (41.22 mN), followed by iris hooks (40.82 mN) and the Malyugin ring (18.56 mN).
Our study predicted that current pupil expanders exert significantly higher amount of stresses and forces than required during pupil expansion. Our work may serve as a guide for the development and design of next-generation pupil expanders.
A recent study found that a combination of 6 anterior segment optical coherence tomography (ASOCT) parameters (anterior chamber area, volume, and width ACA, ACV, ACW, lens vault LV, iris thickness at ...750 μm from the scleral spur, and iris cross-sectional area) explain >80% of the variability in angle width. The aim of this study was to evaluate classification algorithms based on ASOCT measurements for the detection of gonioscopic angle closure.
Cross-sectional study.
We included 2047 subjects aged ≥50 years.
Participants underwent gonioscopy and ASOCT (Carl Zeiss Meditec, Dublin, CA). Customized software (Zhongshan Angle Assessment Program, Guangzhou, China) was used to measure ASOCT parameters in horizontal ASOCT scans. Six classification algorithms were considered (stepwise logistic regression with Akaike information criterion, Random Forest, multivariate adaptive regression splines, support vector machine, naïve Bayes' classification, and recursive partitioning). The ASOCT-derived parameters were incorporated to generate point and interval estimates of the area under the receiver operating characteristic (AUC) curves for these algorithms using 10-fold cross-validation as well as 50:50 training and validation.
We assessed ASOCT measurements and angle closure.
Data on 1368 subjects, including 295 (21.6%) subjects with gonioscopic angle closure were available for analysis. The mean (±standard deviation) age was 62.4±7.5 years and 54.8% were females. Angle closure subjects were older and had smaller ACW, ACA, and ACV; greater LV; and thicker irides (P<0.001 for all). For both, the 10-fold cross-validation and the 50:50 training and validation methods, stepwise logistic regression was the best algorithm for detecting eyes with gonioscopic angle closure with testing set AUC of 0.954 (95% confidence interval CI, 0.942-0.966) and 0.962 (95% CI, 0.948-0.975) respectively, whereas recursive partitioning had relatively the poorest performance with testing set AUC 0.860 (95% CI, 0.790-0.930) and 0.905 (95% CI, 0.876-0.933), respectively. This algorithm performed similarly well (AUC, 0.957) in a second independent sample of 200 angle closure subjects and 302 normal controls.
A classification algorithm based on stepwise logistic regression that used a combination of 6 parameters obtained from a single horizontal ASOCT scan identified subjects with gonioscopic angle closure>95% of the time.
The authors have no proprietary or commercial interest in any of the materials discussed in this article.
To identify subgroups of primary angle-closure suspects (PACS) based on anterior segment optical coherence tomography (AS-OCT) and biometric parameters.
Cross-sectional study.
We evaluated 243 PACS ...subjects in the primary group and 165 subjects in the validation group.
Participants underwent gonioscopy and AS-OCT (Carl Zeiss Meditec, Dublin, CA). Customized software (Zhongshan Angle Assessment Program, Guangzhou, China) was used to measure AS-OCT parameters. An agglomerative hierarchical clustering method was first used to determine the optimum number of parameters to be included in the determination of subgroups. The best number of subgroups was then determined using Akaike Information Criterion (AIC) and Gaussian Mixture Model (GMM) methods.
Subgroups of PACS.
The mean age of the subjects was 64.8 years, and 65.02% were female. After hierarchical clustering, 1 or 2 parameters from each cluster were chosen to ensure representativeness of the parameters and yet keep a minimum of redundancy. The parameters included were iris area, anterior chamber depth (ACD), anterior chamber width (ACW), and lens vault (LV). With the use of GMM, the optimal number of subgroups as given by AIC was 3. Subgroup 1 was characterized by a large iris area, subgroup 2 was characterized by a large LV and a shallow ACD, and subgroup 3 was characterized by elements of both subgroups 1 and 2. The results were replicated in a second independent group of 165 PACS subjects.
Clustering analysis identified 3 distinct subgroups of PACS subjects based on AS-OCT and biometric parameters. These findings may be relevant for understanding angle-closure pathogenesis and management.
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