Are Macula or Optic Nerve Head Structures Better at Diagnosing Glaucoma? An Answer Using Artificial Intelligence and Wide-Field Optical Coherence Tomography.

Purpose: We wanted to develop a deep-learning algorithm to automatically segment optic nerve head (ONH) and macula structures in three-dimensional (3D) wide-field optical coherence tomography (OCT) scans and to assess whether 3D ONH or macula structures (or a combination of both) provide the best diagnostic power for glaucoma. Methods: A cross-sectional comparative study was performed using 319 OCT scans of glaucoma eyes and 298 scans of nonglaucoma eyes. Scans were compensated to improve deep-tissue visibility. We developed a deep-learning algorithm to automatically label major tissue structures, trained with 270 manually annotated B-scans. The performance was assessed using the Dice coefficient (DC). A glaucoma classification algorithm (3D-CNN) was then designed using 500 OCT volumes and corresponding automatically segmented labels. This algorithm was trained and tested on three datasets: cropped scans of macular tissues, those of ONH tissues, and wide-field scans. The classification performance for each dataset was reported using the area under the curve (AUC). Results: Our segmentation algorithm achieved a DC of 0.94 ± 0.003. The classification algorithm was best able to diagnose glaucoma using wide-field scans, followed by ONH scans, and finally macula scans, with AUCs of 0.99 ± 0.01, 0.93 ± 0.06 and 0.91 ± 0.11, respectively. Conclusions: This study showed that wide-field OCT may allow for significantly improved glaucoma diagnosis over typical OCTs of the ONH or macula. Translational Relevance: This could lead to mainstream clinical adoption of 3D wide-field OCT scan technology.

The Structural Layers of the Porcine Iris Exhibit Inherently Different Biomechanical Properties.

Purpose: The purpose of this study was to isolate the structural components of the ex vivo porcine iris tissue and to determine their biomechanical properties. Methods: The porcine stroma and dilator tissues were separated, and their dimensions were assessed using optical coherence tomography (OCT). The stroma underwent flow test (n = 32) to evaluate for permeability using Darcy's Law (ΔP = 2000 Pa, A = 0.0391 mm2), and both tissues underwent stress relaxation experiments (ε = 0.5 with initial ramp of δε = 0.1) to evaluate for their viscoelastic behaviours (n = 28). Viscoelasticity was characterized by the parameters ß (half width of the Gaussian distribution), τm (mean relaxation time constant), E0 (instantaneous modulus), and E∞ (equilibrium modulus). Results: For the stroma, the hydraulic permeability was 9.49 ± 3.05 × 10-6 mm2/Pa · s, and the viscoelastic parameters were ß = 2.50 ± 1.40, and τm = 7.43 ± 4.96 s, with the 2 moduli calculated to be E0 = 14.14 ± 6.44 kPa and E∞ = 6.08 ± 2.74 kPa. For the dilator tissue, the viscoelastic parameters were ß = 2.06 ± 1.33 and τm = 1.28 ± 1.27 seconds, with the 2 moduli calculated to be E0 = 9.16 ± 3.03 kPa and E∞ = 5.54 ± 1.98 kPa. Conclusions: We have established a new protocol to evaluate the biomechanical properties of the structural layers of the iris. Overall, the stroma was permeable and exhibited smaller moduli than those of the dilator muscle. An improved characterization of iris biomechanics may form the basis to further our understanding of angle closure glaucoma.

A Duration-Dependent Interaction Between High-Intensity Light and Unrestricted Vision in the Drive for Myopia Control.

Purpose: To evaluate the duration-dependent and synergetic impact of high-intensity light (HL) and unrestricted vision (UnV) on lens-induced myopia (LIM) development in chickens. Methods: Myopia was induced in one eye in chicks (10 groups, n = 126) from day 1 posthatching (D1) until day 8 (D8) using -10 diopter (D) lenses. Fellow eyes remained uncovered as controls. Nine groups were exposed daily to 2, 4, or 6 hours of HL (15,000 lux), UnV (removal of -10 D lens), or both (HL + UnV). One group served as the LIM group without any interventions. Ocular axial length (AL), refractive error, and choroidal thickness were measured on D1, D4, and D8. Outcome measures are expressed as interocular difference (IOD = experimental eye - control eye) ± SEM. Results: By D8, LIM increased AL (0.36 ± 0.04 mm), myopic refraction (-9.02 ± 0.37 D), and choroidal thinning (-90.27 ± 16.44 µm) in the LIM group (all, P < 0.001). Compared to the LIM group, exposure to 2, 4, or 6 hours of HL, UnV, or HL + UnV reduced myopic refraction in a duration-dependent manner, with UnV being more effective than HL (P < 0.05). Only 6 hours of HL + UnV (not 2 or 4 hours) prevented LIM and was more effective than UnV (P = 0.004) or HL (P < 0.001) in reducing myopic refraction and more effective than HL (P < 0.001) in reducing axial elongation. Conclusions: Daily exposure to 2, 4, or 6 hours of HL, UnV, or HL + UnV reduced lens-induced myopic refraction in a duration-dependent manner in chickens. Only 6 hours of HL + UnV completely stopped LIM development. The synergetic effect of HL and UnV is dependent on the duration of the interventions.

Changes in Iris Stiffness and Permeability in Primary Angle Closure Glaucoma.

Purpose: To evaluate the biomechanical properties of the iris by evaluating iris movement during pupil constriction and to compare such properties between healthy and primary angle-closure glaucoma (PACG) subjects. Methods: A total of 140 subjects were recruited for this study. In a dark room, the anterior segments of one eye per subject were scanned using anterior segment optical coherence tomography imaging during induced pupil constriction with an external white light source of 1700 lux. Using a custom segmentation code, we automatically isolated the iris segments from the AS-OCT images, which were then discretized and transformed into a three-dimensional point cloud. For each iris, a finite element (FE) mesh was constructed from the point cloud, and an inverse FE simulation was performed to match the clinically observed iris constriction in the AS-OCT images. Through this optimization process, we were able to identify the elastic modulus and permeability of each iris. Results: For all 140 subjects (95 healthy and 45 PACG of Indian/Chinese ethnicity; age 60.2 ± 8.7 for PACG subjects and 57.7 ± 10.1 for healthy subjects), the simulated deformation pattern of the iris during pupil constriction matched well with OCT images. We found that the iris stiffness was higher in PACG than in healthy controls (24.5 ± 8.4 kPa vs. 17.1 ± 6.6 kPa with 40 kPa of active stress specified in the sphincter region; P < 0.001), whereas iris permeability was lower (0.41 ± 0.2 mm2/kPa s vs. 0.55 ± 0.2 mm2/kPa s; p = 0.142). Conclusions: This study suggests that the biomechanical properties of the iris in PACG are different from those in healthy controls. An improved understanding of the biomechanical behavior of the iris may have implications for the understanding and management of angle-closure glaucoma.

Ocular growth and metabolomics are dependent upon the spectral content of ambient white light.

Myopia results from an excessive axial growth of the eye, causing abnormal projection of remote images in front of the retina. Without adequate interventions, myopia is forecasted to affect 50% of the world population by 2050. Exposure to outdoor light plays a critical role in preventing myopia in children, possibly through the brightness and blue-shifted spectral composition of sunlight, which lacks in artificial indoor lighting. Here, we evaluated the impact of moderate levels of ambient standard white (SW: 233.1 lux, 3900 K) and blue-enriched white (BEW: 223.8 lux, 9700 K) lights on ocular growth and metabolomics in a chicken-model of form-deprivation myopia. Compared to SW light, BEW light decreased aberrant ocular axial elongation and accelerated recovery from form-deprivation. Furthermore, the metabolomic profiles in the vitreous and retinas of recovering form-deprived eyes were distinct from control eyes and were dependent on the spectral content of ambient light. For instance, exposure to BEW light was associated with deep lipid remodeling and metabolic changes related to energy production, cell proliferation, collagen turnover and nitric oxide metabolism. This study provides new insight on light-dependent modulations in ocular growth and metabolomics. If replicable in humans, our findings open new potential avenues for spectrally-tailored light-therapy strategies for myopia.

Performance of a temperature-controlled shape-memory pupil expander for cataract surgery.

PURPOSE: To perform ex vivo and in vivo validation of a manufactured, optimized shape-memory pupil expander and compare its performance to that of existing devices. SETTING: National University of Singapore and SingHealth Academy. DESIGN: Prospective randomized blinded assessment. METHODS: Shape-memory expanders were manufactured by overmolding and were inserted into ex vivo porcine eyes and in vivo monkey eyes for validation. The shape-memory expander was compared to the Malyugin ring, OASIS iris expander, and iris hook. After insertion and removal of the devices, the eyes were fixed, and the iris images were analyzed. RESULTS: The shape-memory was successful in pupil expansion for both in vivo and ex vivo experiments. Subsequent ex vivo device comparison revealed iris pigment epithelial loss in 36.4% of eyes for the iris hooks, 30.8% for the iris expander, and 20.0% for the Malyugin ring. Sphincter tears were observed in 27.3% of eyes for the iris hooks and 10.0% for the Malyugin ring. No observable tissue irregularities were observed in the shape-memory expander. CONCLUSION: The shape-memory expander was optimized to minimize stress exerted onto the iris tissue. The in vivo and ex vivo experimental validation demonstrate efficacy in engineering design and further highlight the translational potential of smart materials in implant development to improve patient healthcare.

Permeability of the porcine iris stroma.

Current literature has not considered or provided any data on the permeability of the iris stroma. In this study, we aimed to determine the hydraulic permeability of porcine irides from the isolated stroma. Fifteen enucleated porcine eyes were acquired from the local abattoir. The iris pigment epithelium was scraped off using a pair of forceps and the dilator muscles were pinched off using a pair of colibri toothed forceps. We designed an experimental setup, based on Darcy's law, and consisting of a custom 3D-printed pressure column using acrylonitrile butadiene styrene (ABS) plastic. PBS solution was passed through the iris stroma in a 180° arc shape, with a column height of approximately 204 mm (2000 Pa). Measurements of iris stromal thickness were conducted using optical coherence tomography (OCT). To measure flow rate, we measured the mass (volume) of PBS solution using a mass balance in approximately 1 min. Histology was performed using hematoxylin and eosin (H&E) and anti-smooth muscle antibody (anti-α-SMA) for validation. The permeability experiments demonstrated that the iris stroma is a biphasic tissue that allows fluid flow. Our image processing results determined the area of flow to be 7.55 mm2 and the tissue thickness to be between 180 and 430 µm. The hydraulic permeability of the porcine stroma, calculated using Darcy's law, was 5.13 ±â€¯2.39 × 10-5 mm2/Pa•s. Histological and immunochemical studies confirmed that the tissues used for this permeability study were solely iris stroma. Additionally, anti-α-SMA staining revealed staining specific for stromal blood vessels, with the notable absence of dilator and sphincter muscle staining. Our study combined experimental microscopic data with the theory of biphasic materials to investigate the hydraulic permeability of the iris stroma. This work will serve as a basis on which to validate future biomechanical studies of human irides with which may ultimately aid disease diagnosis and inform the design of novel treatments.

Numerical stress analysis of the iris tissue induced by pupil expansion: Comparison of commercial devices.

PURPOSE: (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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.