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16 pages, 4824 KiB

Open AccessArticle

Corneal Surface Wave Propagation Associated with Intraocular Pressures: OCT Elastography Assessment in a Simplified Eye Model

by Guoqin Ma, Jing Cai, Rijian Zhong, Weichao He, Haoxi Ye, Chaitanya Duvvuri, Chengjin Song, Jinping Feng, Lin An, Jia Qin, Yanping Huang, Jingjiang Xu, Michael D. Twa and Gongpu Lan

Bioengineering 2023, 10(7), 754; https://doi.org/10.3390/bioengineering10070754 - 24 Jun 2023

Viewed by 1173

Abstract

Assessing corneal biomechanics in vivo has long been a challenge in the field of ophthalmology. Despite recent advances in optical coherence tomography (OCT)-based elastography (OCE) methods, controversy remains regarding the effect of intraocular pressure (IOP) on mechanical wave propagation speed in the cornea. [...] Read more.

Assessing corneal biomechanics in vivo has long been a challenge in the field of ophthalmology. Despite recent advances in optical coherence tomography (OCT)-based elastography (OCE) methods, controversy remains regarding the effect of intraocular pressure (IOP) on mechanical wave propagation speed in the cornea. This could be attributed to the complexity of corneal biomechanics and the difficulties associated with conducting in vivo corneal shear-wave OCE measurements. We constructed a simplified artificial eye model with a silicone cornea and controllable IOPs and performed surface wave OCE measurements in radial directions (54–324°) of the silicone cornea at different IOP levels (10–40 mmHg). The results demonstrated increases in wave propagation speeds (mean ± STD) from 6.55 ± 0.09 m/s (10 mmHg) to 9.82 ± 0.19 m/s (40 mmHg), leading to an estimate of Young’s modulus, which increased from 145.23 ± 4.43 kPa to 326.44 ± 13.30 kPa. Our implementation of an artificial eye model highlighted that the impact of IOP on Young’s modulus (ΔE = 165.59 kPa, IOP: 10–40 mmHg) was more significant than the effect of stretching of the silicone cornea (ΔE = 15.79 kPa, relative elongation: 0.98–6.49%). Our study sheds light on the potential advantages of using an artificial eye model to represent the response of the human cornea during OCE measurement and provides valuable insights into the impact of IOP on wave-based OCE measurement for future in vivo corneal biomechanics studies. Full article

(This article belongs to the Special Issue Ophthalmic Engineering)

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17 pages, 2984 KiB

Open AccessArticle

Recreating the Trabecular Outflow Tissue on Implantable, Micropatterned, Ultrathin, Porous Polycaprolactone Scaffolds

by Luke A. Beardslee, Justin R. Halman, Andrea M. Unser, Yubing Xie, John Danias, Magnus Bergkvist, Susan T. Sharfstein and Karen Y. Torrejon

Bioengineering 2023, 10(6), 679; https://doi.org/10.3390/bioengineering10060679 - 02 Jun 2023

Cited by 2 | Viewed by 1150

Abstract

Glaucoma, where increased intraocular pressure (IOP) leads to damage to the optic nerve and loss of sight, is amongst the foremost causes of irreversible blindness worldwide. In primary open angle glaucoma, the increased IOP is a result of the malfunctioning human trabecular meshwork [...] Read more.

Glaucoma, where increased intraocular pressure (IOP) leads to damage to the optic nerve and loss of sight, is amongst the foremost causes of irreversible blindness worldwide. In primary open angle glaucoma, the increased IOP is a result of the malfunctioning human trabecular meshwork (HTM) cells’ inability to properly regulate the outflow of aqueous humor from the eye. A potential future treatment for glaucoma is to replace damaged HTM cells with a tissue-engineered substitute, thus restoring proper fluid outflow. Polycaprolactone (PCL) is a versatile, biodegradable, and implantable material that is widely used for cell culture and tissue engineering. In this work, PCL scaffolds were lithographically fabricated using a sacrificial process to produce submicron-thick scaffolds with openings of specific sizes and shapes (e.g., grid, hexagonal pattern). The HTM cell growth on gelatin-coated PCL scaffolds was assessed by scanning electron microscopy, tetrazolium metabolic activity assay, and cytoskeletal organization of F-actin. Expression of HTM-specific markers and ECM deposition were assessed by immunocytochemistry and qPCR analysis. Gelatin-coated, micropatterned, ultrathin, porous PCL scaffolds with a grid pattern supported proper HTM cell growth, cytoskeleton organization, HTM-marker expression, and ECM deposition, demonstrating the feasibility of using these PCL scaffolds to tissue-engineer implantable, healthy ocular outflow tissue. Full article

(This article belongs to the Special Issue Ophthalmic Engineering)

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13 pages, 6282 KiB

Open AccessArticle

An Inverse Method to Determine Mechanical Parameters of Porcine Vitreous Bodies Based on the Indentation Test

by Haicheng Zu, Kunya Zhang, Haixia Zhang and Xiuqing Qian

Bioengineering 2023, 10(6), 646; https://doi.org/10.3390/bioengineering10060646 - 26 May 2023

Cited by 1 | Viewed by 937

Abstract

The vitreous body keeps the lens and retina in place and protects these tissues from physical insults. Existing studies have reported that the mechanical properties of vitreous body varied after liquefaction, suggesting mechanical properties could be effective parameters to identify vitreous liquefaction process. [...] Read more.

The vitreous body keeps the lens and retina in place and protects these tissues from physical insults. Existing studies have reported that the mechanical properties of vitreous body varied after liquefaction, suggesting mechanical properties could be effective parameters to identify vitreous liquefaction process. Thus, in this work, we aimed to propose a method to determine the mechanical properties of vitreous bodies. Fresh porcine eyes were divided into three groups, including the untreated group, the 24 h liquefaction group and the 48 h liquefaction group, which was injected collagenase and then kept for 24 h or 48 h. The indentation tests were carried out on the vitreous body in its natural location while the posterior segment of the eye was fixed in the container. A finite element model of a specimen undertaking indentation was constructed to simulate the indentation test with surface tension of vitreous body considered. Using the inverse method, the mechanical parameters of the vitreous body and the surface tension coefficient were determined. For the same parameter, values were highest in the untreated group, followed by the 24 h liquefaction group and the lowest in the 48 h liquefaction group. For C₁₀ in the neo-Hookean model, the significant differences were found between the untreated group and liquefaction groups. This work quantified vitreous body mechanical properties successfully using inverse method, which provides a new method for identifying vitreous liquefactions related studies. Full article

(This article belongs to the Special Issue Ophthalmic Engineering)

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14 pages, 4296 KiB

Open AccessArticle

The Corneal Ectasia Model of Rabbit: A Validity and Stability Study

by Junchao Wei, Rui He, Xiaogang Wang, Yaowen Song, Jinhan Yao, Xiaona Liu, Xin Yang, Weiyi Chen and Xiaona Li

Bioengineering 2023, 10(4), 479; https://doi.org/10.3390/bioengineering10040479 - 16 Apr 2023

Cited by 3 | Viewed by 1392

Abstract

Keratoconus is a bilateral progressive degenerative corneal disease characterized by localized corneal thinning and dilatation. The pathogenesis of keratoconus is not fully elucidated. To gain a better understanding of the pathophysiology of this disease and to explore potential treatments, animal models are essential [...] Read more.

Keratoconus is a bilateral progressive degenerative corneal disease characterized by localized corneal thinning and dilatation. The pathogenesis of keratoconus is not fully elucidated. To gain a better understanding of the pathophysiology of this disease and to explore potential treatments, animal models are essential for basic research. Several attempts have been made to establish animal models of corneal ectasia by using collagenase. However, continuous changes of the cornea have not been well-tracked for the model. In this study, corneal morphology and biomechanical behavior in vivo were determined before and after collagenase Ⅱ treatment at 2, 4, and 8 weeks. The elastic modulus and histology of cornea tissues ex vivo were measured at 8 weeks postoperatively. The results showed that the posterior corneal curvature (Km B) increased and central corneal thickness (CCT) decreased after collagenase treatment. The mechanical properties of ectatic corneas weakened significantly and the collagen fiber interval in the stromal layer was increased and disorganized. This study provides insights into the changes of corneal morphology and biomechanical properties in a rabbit model of corneal ectasia. Changes observed at 8 weeks indicated that the cornea was still undergoing remodeling. Full article

(This article belongs to the Special Issue Ophthalmic Engineering)

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14 pages, 2606 KiB

Open AccessArticle

Application of a Magnetic Platform in α6 Integrin-Positive iPSC-TM Purification

by Pengchao Feng, Wenyan Wang, Wenhua Xu, Qilong Cao and Wei Zhu

Bioengineering 2023, 10(4), 410; https://doi.org/10.3390/bioengineering10040410 - 25 Mar 2023

Viewed by 1090

Abstract

The emergence of induced pluripotent stem cell (iPSC) technology has provided a new approach to regenerating decellularized trabecular meshwork (TM) in glaucoma. We have previously generated iPSC-derived TM (iPSC-TM) using a medium conditioned by TM cells and verified its function in tissue regeneration. [...] Read more.

The emergence of induced pluripotent stem cell (iPSC) technology has provided a new approach to regenerating decellularized trabecular meshwork (TM) in glaucoma. We have previously generated iPSC-derived TM (iPSC-TM) using a medium conditioned by TM cells and verified its function in tissue regeneration. Because of the heterogeneity of iPSCs and the isolated TM cells, iPSC-TM cells appear to be heterogeneous, which impedes our understanding of how the decellularized TM may be regenerated. Herein, we developed a protocol based on a magnetic-activated cell sorting (MACS) system or an immunopanning (IP) method for sorting integrin subunit alpha 6 (ITGA6)-positive iPSC-TM, an example of the iPSC-TM subpopulation. We first analyzed the purification efficiency of these two approaches by flow cytometry. In addition, we also determined cell viability by analyzing the morphologies of the purified cells. To conclude, the MACS-based purification could yield a higher ratio of ITGA6-positive iPSC-TM and maintain a relatively higher cell viability than the IP-based method, allowing for the preparation of any iPSC-TM subpopulation of interest and facilitating a better understanding of the regenerative mechanism of iPSC-based therapy. Full article

(This article belongs to the Special Issue Ophthalmic Engineering)

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12 pages, 4641 KiB

Open AccessArticle

Design of an Automatically Controlled Multi-Axis Stretching Device for Mechanical Evaluations of the Anterior Eye Segment

by Kehao Wang, Ziyan Qiu, Yiping Xie, Shuo Cai, Yang Zhao, Barbara K. Pierscionek, Jiangzhen Guo and Yubo Fan

Bioengineering 2023, 10(2), 142; https://doi.org/10.3390/bioengineering10020142 - 20 Jan 2023

Viewed by 1674

Abstract

The young eye has an accommodative ability involving lens shape changes to focus over different distances. This function gradually decreases with age, resulting in presbyopia. Greater insights into the mechanical properties of anterior eye structures can improve understanding of the causes of presbyopia. [...] Read more.

The young eye has an accommodative ability involving lens shape changes to focus over different distances. This function gradually decreases with age, resulting in presbyopia. Greater insights into the mechanical properties of anterior eye structures can improve understanding of the causes of presbyopia. The present study aims to develop a multi-axis stretching device for evaluating the mechanical properties of the intact eye lens. A stretching device integrating the mechanical stretcher, motor, torque sensor and data transmission mechanism was designed and developed by 3D printing. The mechanical stretcher can convert rotation into radial movement, both at constant speeds, according to the spiral of Archimedes. The loading unit equipped with eight jaws can hold the eye sample tightly. The developed device was validated with a spring of known constant and was further tested with anterior porcine eye segments. The validation experiment using the spring resulted in stiffness values close to the theoretical spring constant. Findings from measurements with porcine eye samples indicated that the measured forces are within the ranges reported in the literature. The developed multi-axis stretching device has good repeatability during experiments with similar settings and can be reliably used for mechanical evaluations of the intact eye lens. Full article

(This article belongs to the Special Issue Ophthalmic Engineering)

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16 pages, 6406 KiB

Open AccessArticle

Morphological Changes of Glial Lamina Cribrosa of Rats Suffering from Chronic High Intraocular Pressure

by Jingxi Zhang, Yushu Liu, Liu Liu, Lin Li and Xiuqing Qian

Bioengineering 2022, 9(12), 741; https://doi.org/10.3390/bioengineering9120741 - 30 Nov 2022

Viewed by 1390

Abstract

Deformations or remodeling of the lamina cribrosa (LC) induced by elevated intraocular pressure (IOP) are associated with optic nerve injury. The quantitative analysis of the morphology changes of the LC will provide the basis for the study of the pathogenesis of glaucoma. After [...] Read more.

Deformations or remodeling of the lamina cribrosa (LC) induced by elevated intraocular pressure (IOP) are associated with optic nerve injury. The quantitative analysis of the morphology changes of the LC will provide the basis for the study of the pathogenesis of glaucoma. After the chronic high-IOP rat model was induced by cauterizing episcleral veins with 5-Fluorouracil subconjunctival injection, the optic nerve head (ONH) cross sections were immunohistochemically stained at 2 w, 4 w, 8 w, and 12 w. Then the sections were imaged by a confocal microscope, and six morphological parameters of the ONH were calculated after the images were processed using Matlab. The results showed that the morphology of the ONH changed with the duration of chronic high IOP. The glial LC pore area fraction, the ratio of glial LC pore area to the glial LC tissue area, first decreased at 2 w and 4 w and then increased to the same level as the control group at 8 w and continued to increase until 12 w. The number and density of nuclei increased significantly at 8 w in the glial LC region. The results might mean the fraction of glial LC beam increased and astrocytes proliferated at the early stage of high IOP. Combined with the images of the ONH, the results showed the glial LC was damaged with the duration of chronic elevated IOP. Full article

(This article belongs to the Special Issue Ophthalmic Engineering)

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18 pages, 1469 KiB

Open AccessArticle

Differences in the Visual Performances of Patients with Strabismus, Amblyopia, and Healthy Controls

by Danjela Ibrahimi, Juvenal Rodríguez-Reséndiz and Jorge Domingo Mendiola-Santibañez

Bioengineering 2022, 9(11), 626; https://doi.org/10.3390/bioengineering9110626 - 29 Oct 2022

Cited by 1 | Viewed by 1814

Abstract

The aim of this paper is to use the new definition of amblyopia and to define the overall visual performance of healthy controls (HCs), patients with strabismus (PS), and patients with refractive amblyopia (PRA), based on the interaction of selected visual abilities. Method: [...] Read more.

The aim of this paper is to use the new definition of amblyopia and to define the overall visual performance of healthy controls (HCs), patients with strabismus (PS), and patients with refractive amblyopia (PRA), based on the interaction of selected visual abilities. Method: A total of 398 participants were divided in three groups: HCs, PRA, and PS. Variables such as visual acuity, refractive state, degree of stereopsis, phoria state, magnitude, and type of deviation were analyzed using parametric and non-parametric tests. Results: Binocular visual acuity at near is the unique predictor factor for stereopsis in PRA and PS, while age relates to the amount of binocular visual acuity at near, only for PS with stereopsis. Binocular visual acuity at near and phoria states relate to each other in PRA. Binocular visual acuity at near and far in PS is better than PRA, with no differences in the degree of stereopsis. Stereoblind patients were only found among PS (36%). Only (44.9%) of PS had amblyopia. Exophoria predominated among PRA (69.72%) and HCs (78.87%), while exotropia was the predominant deviation in PS (60.54%). Hyperopia was the predominate refractive error among the groups, HCs (74.65%), PRA (79.82%), and PS (59.85%), followed by astigmatism. Interpretation: HCs perform better than PS and PRA. The visual performance of PS with stereopsis and PRA is similar. Binocular visual acuity at near can predict the degree of stereopsis, and stereoblind patients are exclusively related to strabismus. Full article

(This article belongs to the Special Issue Ophthalmic Engineering)

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12 pages, 959 KiB

Open AccessArticle

Optimization of a Plasma Rich in Growth Factors Membrane for the Treatment of Inflammatory Ocular Diseases

by Eduardo Anitua, María de la Fuente, Jesús Merayo-Lloves and Francisco Muruzabal

Bioengineering 2022, 9(10), 508; https://doi.org/10.3390/bioengineering9100508 - 27 Sep 2022

Cited by 3 | Viewed by 1284

Abstract

The main purpose of the present study is to develop an immunosafe fibrin membrane obtained by plasma rich in growth factors technology (is-mPRGF) with improved mechanical properties that could be applied in patients with inflammatory ocular diseases. Blood was drawn from three healthy [...] Read more.

The main purpose of the present study is to develop an immunosafe fibrin membrane obtained by plasma rich in growth factors technology (is-mPRGF) with improved mechanical properties that could be applied in patients with inflammatory ocular diseases. Blood was drawn from three healthy donors and centrifuged, and the collected PRGF was activated and distributed into two groups: (i) mPRGF: a PRGF membrane maintained at 37 °C for 30 min; (ii) IS5+30: mPRGF incubated at 37 °C for 5 min and then incubated at 56 °C for 30 min. The content of both membranes was analyzed for several growth factors such as IgE and the complement activation, as well as biological activity on different ocular surface cells. Furthermore, the physical and mechanical characterizations were also evaluated. IS5+30 completely reduced the complement activity and decreased the IgE while preserving the concentration of the main growth factors. IS5+30 induced similar biological activity regarding mPRGF on the different ocular surface cells analyzed. Furthermore, no significant differences in release kinetics or fibrin degradation were observed between both membranes. Summarizing, IS5+30 totally reduces complement activity while preserving the concentration of most growth factors and their biological activity. Furthermore, the physical and mechanical properties of the fibrin membrane are preserved after heat inactivation. Full article

(This article belongs to the Special Issue Ophthalmic Engineering)

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11 pages, 10386 KiB

Open AccessArticle

Corneal Adhesion Possesses the Characteristics of Solid and Membrane

by Jiajin Yang, Qiaomei Ren, Dong Zhao, Zhipeng Gao, Xiaona Li, Rui He and Weiyi Chen

Bioengineering 2022, 9(8), 394; https://doi.org/10.3390/bioengineering9080394 - 16 Aug 2022

Cited by 1 | Viewed by 1395

Abstract

Adhesion behavior usually occurs in corneas associated with clinical treatments. Physiologically, an intact natural cornea is inflated by intraocular pressure. Due to the inflation, the physiological cornea has a mechanical property likeness to membrane. This characteristic is ignored by the classical theory used [...] Read more.

Adhesion behavior usually occurs in corneas associated with clinical treatments. Physiologically, an intact natural cornea is inflated by intraocular pressure. Due to the inflation, the physiological cornea has a mechanical property likeness to membrane. This characteristic is ignored by the classical theory used to analyze the adhesion behavior of soft solids, such as the Johnson–Kendall–Roberts (JKR) model. Performing the pull-off test, this work evidenced that the classical JKR solution was suitable for computing the corneal adhesion force corresponding to the submillimeter scale of contact. However, when the cornea was contacted at a millimeter scale, the JKR solutions were clearly smaller than the related experimental data. The reason was correlated with the membranous characteristic of the natural cornea was not considered in the JKR solid model. In this work, the modified JKR model was superimposed by the contribution from the surface tension related to the corneal inflation due to the intraocular pressure. It should be treated as a solid when the cornea is contacted at a submillimeter scale, whereas for the contact at a larger size, the characteristic of the membrane should be considered in analyzing the corneal adhesion. The modified JKR model successfully described the adhesion characteristics of the cornea from solid to membrane. Full article

(This article belongs to the Special Issue Ophthalmic Engineering)

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13 pages, 1790 KiB

Open AccessReview

In Vivo Biomechanical Measurements of the Cornea

by Fanshu Li, Kehao Wang and Ziyuan Liu

Bioengineering 2023, 10(1), 120; https://doi.org/10.3390/bioengineering10010120 - 15 Jan 2023

Cited by 3 | Viewed by 2076

Abstract

In early corneal examinations, the relationships between the morphological and biomechanical features of the cornea were unclear. Although consistent links have been demonstrated between the two in certain cases, these are not valid in many diseased states. An accurate assessment of the corneal [...] Read more.

In early corneal examinations, the relationships between the morphological and biomechanical features of the cornea were unclear. Although consistent links have been demonstrated between the two in certain cases, these are not valid in many diseased states. An accurate assessment of the corneal biomechanical properties is essential for understanding the condition of the cornea. Studies on corneal biomechanics in vivo suggest that clinical problems such as refractive surgery and ectatic corneal disease are closely related to changes in biomechanical parameters. Current techniques are available to assess the mechanical characteristics of the cornea in vivo. Accordingly, various attempts have been expended to obtain the relevant mechanical parameters from different perspectives, using the air-puff method, ultrasound, optical techniques, and finite element analyses. However, a measurement technique that can comprehensively reflect the full mechanical characteristics of the cornea (gold standard) has not yet been developed. We review herein the in vivo measurement techniques used to assess corneal biomechanics, and discuss their advantages and limitations to provide a comprehensive introduction to the current state of technical development to support more accurate clinical decisions. Full article

(This article belongs to the Special Issue Ophthalmic Engineering)

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14 pages, 1719 KiB

Open AccessReview

A Review of the Methods of Non-Invasive Assessment of Intracranial Pressure through Ocular Measurement

by Jinhui Dong, Qi Li, Xiaofei Wang and Yubo Fan

Bioengineering 2022, 9(7), 304; https://doi.org/10.3390/bioengineering9070304 - 11 Jul 2022

Cited by 6 | Viewed by 2538

Abstract

The monitoring of intracranial pressure (ICP) is essential for the detection and treatment of most craniocerebral diseases. Invasive methods are the most accurate approach to measure ICP; however, these methods are prone to complications and have a limited range of applications. Therefore, non-invasive [...] Read more.

The monitoring of intracranial pressure (ICP) is essential for the detection and treatment of most craniocerebral diseases. Invasive methods are the most accurate approach to measure ICP; however, these methods are prone to complications and have a limited range of applications. Therefore, non-invasive ICP measurement is preferable in a range of scenarios. The current non-invasive ICP measurement methods comprise fluid dynamics, and ophthalmic, otic, electrophysiological, and other methods. This article reviews eight methods of non-invasive estimation of ICP from ocular measurements, namely optic nerve sheath diameter, flash visual evoked potentials, two-depth transorbital Doppler ultrasonography, central retinal venous pressure, optical coherence tomography, pupillometry, intraocular pressure measurement, and retinal arteriole and venule diameter ratio. We evaluated and presented the indications and main advantages and disadvantages of these methods. Although these methods cannot completely replace invasive measurement, for some specific situations and patients, non-invasive measurement of ICP still has great potential. Full article

(This article belongs to the Special Issue Ophthalmic Engineering)

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