Scleral Tissue Research Articles

Elevated IOP Alters the Material Properties of Sclera and Lamina Cribrosa in Monkeys.

Objective Elevated intraocular pressure (IOP) has significant impacts on different stages in the progression of chronic glaucoma. In this study, we investigated changes in the material properties of sclera and lamina cribrosa (LC) in a nonhuman primate model with elevated IOP. Methods Normal adult Tibetan macaques were selected for the construction of elevated IOP model. After 40 days of stable maintenance on the ocular hypertension, the binocular eyeballs were obtained for the measurement of macroscopic parameters of the eyeballs. Posterior scleral tissue strips were obtained in circumferential and axial directions, and thickness was measured, respectively. Biomechanical parameters were obtained with stress relaxation, creep, and tensile test. The nanoindentation test was performed on the LC and scleral tissue around optic nerve head (ONH) to obtain compressive modulus. Results In the presence of elevated IOP, variations of the axial diameter of the eyeball were greater than those of the transverse diameter, and the mean scleral thickness around ONH was smaller in the experimental group than control group. The elastic modulus and stress relaxation modulus of sclera were larger, and the creep rate was lower in the experimental group than control group. In the control group, the elastic modulus and stress relaxation modulus of the circumferential sclera were larger in the axial direction, and creep rate was smaller. In the experimental group, there was no significant difference in biomechanical characteristics between the two directions. Compared to the control group, the compression modulus of the LC was smaller, and the compression modulus of sclera around ONH was larger in the experimental group. Conclusion Elevated IOP alters the viscoelasticity and anisotropy of sclera and LC. These may contribute to reduction of the organizational resistance to external forces and decline in the ability of self-recovery.

Lysyl oxidase-like 1 deficiency alters ultrastructural and biomechanical properties of the peripapillary sclera in mice

Lysyl oxidase-like 1 encoded by the LOXL1 gene is a member of the lysyl oxidase family of enzymes that are important in the maintenance of extracellular matrix (ECM)-rich tissue. LOXL1 is important for proper elastic fiber formation and mice lacking LOXL1 (Loxl1−/−) exhibit systemic elastic fiber disorders, such as pelvic organ prolapse, a phenotype associated with exfoliation syndrome (XFS) in humans. Patients with XFS have a significant risk of developing exfoliation glaucoma (XFG), a severe form of glaucoma, which is a neurodegenerative condition leading to irreversible blindness if not detected and treated in a timely fashion. Although Loxl1−/− mice have been used extensively to investigate mechanisms of pelvic organ prolapse, studies of eyes in those mice are limited and some showed inconsistent ocular phenotypes. In this study we demonstrate that Loxl1−/− mice have significant anterior segment biometric abnormalities which recapitulate some human XFS features. We then focused on the peripapillary sclera (PPS), a critical structure for maintaining optic nerve health. We discovered quantitative and qualitive changes in ultrastructure of PPS, such as reduced elastic fibers, enlarged collagen fibrils, and transformed collagen lamella organization detected by transmission electron microscopy (TEM). Importantly, these changes corelate with altered tissue biomechanics detected by Atomic Force Microscopy (AFM) of PPS in mice. Together, our results support a crucial role for LOXL1 in ocular tissue structure and biomechanics, and Loxl1−/− mice could be a valuable resource for understanding the role of scleral tissue biomechanics in ocular disease.

Modeling and experimental investigation of electromechanical properties of scleral tissue; a CEM model using an anisotropic hyperelastic constitutive relation.

The sclera is a soft tissue primarily consisting of collagen fibers, elastin, and proteoglycans. The proteoglycans are composed of a core protein and negatively chargedglycosaminoglycan side chains. The fixed electric charges inside the scleral extracellular matrix play a key role in its swelling and are expected to cause the tissue to deform in response to an electric field. However, the electroactive response of the sclera has not yet been investigated. The present work experimentally demonstrates that sclera behaves similar to an anionic electrosensitive hydrogel and develops a chemo-electro-mechanical(CEM) mathematical framework for its electromechanical response. In the numerical model, a hyperelastic constitutive law with distributed collagen fibers is used to capture the nonlinear mechanical properties of the sclera, and the coupled Poisson-Nernst-Planck equations represent the distribution of mobile ions throughout the domain. After calibrating the proposed numerical CEMmodel against the experimental measurements, we employ it to investigate the effects of different parameters on the scleral electromechanical response including the voltage and fixed charge density. The experimental and numerical findings of the present study confirm that sclera behaves as an electroactive hydrogel and provide new insight into the mechanical response of this ocular tissue.

Transcriptomic Profiling of Human Limbus-Derived Stromal/Mesenchymal Stem Cells-Novel Mechanistic Insights into the Pathways Involved in Corneal Wound Healing.

Limbus-derived stromal/mesenchymal stem cells (LMSCs) are vital for corneal homeostasis and wound healing. However, despite multiple pre-clinical and clinical studies reporting the potency of LMSCs in avoiding inflammation and scarring during corneal wound healing, the molecular basis for the ability of LMSCs remains unknown. This study aimed to uncover the factors and pathways involved in LMSC-mediated corneal wound healing by employing RNA-Sequencing (RNA-Seq) in human LMSCs for the first time. We characterized the cultured LMSCs at the stages of initiation (LMSC−P0) and pure population (LMSC−P3) and subjected them to RNA-Seq to identify the differentially expressed genes (DEGs) in comparison to native limbus and cornea, and scleral tissues. Of the 28,000 genes detected, 7800 DEGs were subjected to pathway-specific enrichment Gene Ontology (GO) analysis. These DEGs were involved in Wnt, TGF-β signaling pathways, and 16 other biological processes, including apoptosis, cell motility, tissue remodeling, and stem cell maintenance, etc. Two hundred fifty-four genes were related to wound healing pathways. COL5A1 (11.81 ± 0.48) and TIMP1 (20.44 ± 0.94) genes were exclusively up-regulated in LMSC−P3. Our findings provide new insights involved in LMSC-mediated corneal wound healing.

Quantification and comparison of teleost scleral cartilage development and growth.

The ocular skeleton is composed of the scleral cartilage and the scleral ossicles. Teleost scleral cartilage is composed of a single layer of chondrocytes embedded in the sclera of the eye. The teleost scleral cartilage ring can vary in depth across teleost families and species, from a narrow ring a few cells wide to a deeper ring that resembles a cup and surrounds the entire sclera. However, very little research has been conducted on the development and morphology of teleost scleral cartilage. Thus, this study aims to characterize the development of the scleral cartilage in the zebrafish and Mexican tetra, with respect to the timing of emergence, depth throughout development, and positioning within the eye. We hypothesized that the scleral cartilage would first emerge in the scleral tissue closely abutting the ora serrata, and that growth would proceed in an anterior-to-posterior direction, resulting in differences in scleral cartilage depth between different fish species. We found that the scleral cartilage ring does not develop uniformly along its circumference, and that its relationship to the ora serrata varies between the rostral and caudal regions. Furthermore, distinct differences in the growth trajectory of the scleral cartilage indicate that the deep scleral cartilage of the Pachón cavefish is the result of both decreased eye size and prolonged cartilage growth. A significant difference in the size of the scleral chondrocytes was also noted. Overall, this study provides the first characterization of early scleral cartilage development in teleost fish and indicates that some aspects of scleral cartilage development and morphology are highly conserved while others are not.

Efficacy Theory and Proposed Protocol for Presbyopia Correction using Scleral Softening by Non-invasive Infrared Diode Lasers

Purpose: To derive and provide analytic formulas and proposed protocol for accommodative gain of presbyopia eyes via laser scleral softening, which causes increased space between ciliary body and lens (SCL) and mobility of the posterior vitreal zonules (PVZ).
 Study Design: To increase the accommodation of presbyopia by laser scleral heating/softening.
 Place and Duration of Study: New Taipei City, Taiwan, between April 2022 and June 2022.
 Purpose: To analyze the safety and efficacy of presbyopia treatment via scleral softening.
 Methodology: The scleral softening efficacy is calculated based on the rate equation of scleral tissue with a rate coefficient given by an Arrhenius formula, Temperature spatial and temporal profiles are given by the numerical solutions of a heat diffusion equation with a volume heating source. Various effective depths including tissue damage depth, temperature penetration depth and conversion depth, governed by tissue absorption coefficient, light intensity and dose (or irradiation time), and the related threshold values, are introduced in replacing the conventional penetration depth based on a Beer's law.
 Results: Given the the temperature spatial and temporal profiles, scleral softening efficacy can be calculated. Scleral surface damage can be prevented by cooling window. The suggested protocol for scleral softening treatments include: a diode laser at about 1.45 to 1.5 µm or about 1.86 to1.9 µm, or about 2.0 to 2.15 µm, wavelength (with absorption coefficient about 20 to 100 cm-1); laser power about 0.2 to 0.8 W per spot, having a total of 4 to 16 spots; and irradiation time of 100 to 600 ms. Results of corneal thermal shrinkage are demonstrated by the topography changes of pig eyes, in which the scleral softening does not affect the corneal shapes. The accommodative gain is proportional to the softening efficacy (Seff) of the scleral tissue after a thermal laser leading to the increase of PVZ mobility and SCL. However, the actual relation of Seff and the PVZ and SCL changes require measured data.
 Conclusion: Safety and efficacy of scleral softening for presbyopia treatment depend upon the laser parameters (intensity, dose, spot size, wavelength) and the effective depths. By choosing the laser treated areas, a dual function treatment using scleral softening for presbyopia, and cornea stromal shrinkage for hyperopia is proposed and demonstrated by topography of pig eyes.

Accommodative Gain in Presbyopic Eye Using a New Procedure of Laser Scleral Softening (LSS): Part-II. Formulas for Volume Efficacy

Purpose: To derive and provide, for the first time, comprehensive analytic formulas for scleral softening volume efficacy (SVE) for accommodative gain (AG) via the increased space between ciliary body and lens (SCL) and mobility of the posterior vitreous zonules (PVZ).
 Study Design: To increase the AG of presbyopic eye by a new procedure, laser scleral softening (LSS).
 Place and Duration of Study: New Taipei City, Taiwan, between June 2022 and July 2022.
 Methodology: The SVE is calculated based on the time and spatial integral of the scleral temperature profiles, T(z,t), solutions of a heat diffusion equation. Analytic formulas for SVE is derived based on the covered area given by a triangle area. The SVE of a 3-D model is governed by the "volume" covered by the laser beam, or its spot size area, the effective penetration depth (z"), which is an increasing function of laser dose, but a decreasing function of the absorption coefficient (A), due to the Beer's law of laser intensity, I(z)=I0exp(-Az). The efficacy depth-range (dZ) and time-ranges (dT) are defined for efficient softening with T(z,t)>T*, where T* is the scleral softening threshold temperature.
 Results: The accommodative gain is proportional to the 3-D SVE given by: SEV(3D) = SEV(1D) x laser beam spot (2-D area) x total number of spots (N) acting on the sclera, which is proportional to the efficacy ranges dZ and dT, in which dZ is an increasing of laser irradiation time, whereas dT is a decreasing function of depth. Softening of the scleral tissue after a thermal laser leading to the increase of PVZ mobility and SCL. However, the actual relation of SVE and the PVZ and SCL changes require measured data.
 Conclusion: Safety and efficacy of scleral softening for presbyopia treatment depend upon the laser parameters (intensity, dose, spot size, wavelength) and the effective depths. The SVE is proportional to the efficacy depth-range (dZ) and time-range (dT), in which dZ is an increasing of laser irradiation time and dT is a decreasing function of depth. The AG is proportional to the SVE(in 3-D).

Trace elements composition of the scleral shell of the eye in various forms of glaucoma

Purpose: a comparative study of the elemental composition of scleral biopsy specimens from patients with various clinical forms of glaucoma. Material and methods. 44 patients aged 79.5 ± 2.5 were divided into three groups depending on the form of glaucoma: 16 patients with primary open-angle glaucoma (POAG) (group 1); 13 patients with normal tension glaucoma (NTG) (group 2); 15 patients with pseudoexfoliative glaucoma (PEG) (group 3). For elemental analysis, we used scleral biopsies obtained during planned surgical treatment of glaucoma (non-penetrating sinus trabeculectomy). Scleral fragments of 14 donor eyes with no history of glaucoma served as controls. The concentration of macroelements K, Mg, Ca, and Fe was determined using inductively coupled plasma atomic emission spectrometry (ICP-AES, Agilent ICP-AES 720 ES, USA), while microelement concentration (Zn, Cu, Al, Mn) was measured using inductively coupled plasma mass spectrometry (ICP-MS, Bruker ICP-M S 820, Germany). Results. In all forms of glaucoma, scleral samples showed a varying increase in the content of such elements as Zn, Fe, Mg, AL, Ca, K. The highest content of Zn and Fe was found in the scleral tissue of patients with NTG, the difference with the control (p = 0.0001 andp = 0.0003) and with POAG (p = 0.0002, p = 0.0001) being highly significant. The difference between the content of Zn in scleral biopsies of patients with POAG and PEG was also statistically significant (p = 0.0002), whilst no significant difference in Fe content in the sclera (p = 0.69) was found between POAG and PEG Higher Mg concentrations as compared to the control were found in NTG (p = 0.00014) and POAG (p = 0.00002).Patients with POAG (p = 0.0005) and PEG (p = 0.00022) showed the highest accumulation of Ca in the sclera. No differences were found in Mg content of scleral biopsies between patients with NTG and POAG (p = 1.0), while the level of Ca in POAG (p = 0.02) and PEG (p = 0.00001) was significantly higher than in NTG. A significantly lower content of Cu was found in the sclera samples of patients with NTG (p = 0.022), POAG (p = 0.004) and PEG (p = 0.00004) as compared to the control, as well as a reduced content of Mn in POAG (p = 0.00003) and PEG (p = 0.0012). Contrarywise, NTG patients showed an increased content of Mn (p = 0.000003). No differences were found in the Cu content between the sclera of patients with NTG and POAG (p = 0.47), while Cu level in PEG was significantly lower than in POAG (p = 0.034) and NTG (p = 0.013). Conclusion. The macro- and microelement imbalance of the sclera of the eyes with different forms of glaucoma indicates differences in their pathogenesis. This can be the reason for the different severity of disorders of collagen biosynthesis and the formation of cross-links in the connective tissue structures of the sclera, as well as the varying degree changes in the hydrodynamics of the intraocular fluid, which on the whole can affect the level of intraocular pressure and the pattern of glaucoma development.

A report on a series of nanophthalmos with histopathology and immunohistochemistry analyses using light microscopy

We aimed to study the histopathological and immunohistochemistry features in clinically diagnosed cases of nanophthalmos using light microscopy. This was an observational comparative study. We enrolled four eyes of four consecutive patients with nanophthalmos and visually significant cataract, who underwent cataract surgery with prophylactic posterior sclerostomy. Histological analysis of the excised scleral tissue was done and compared with age-matched cadaver controls between January 2021 and October 2021. Hematoxylin and Eosin (H&E) stains were used for histological analysis, and was further supplemented with immunohistochemistry (IHC) and immunofluorescence (IF) analyses using a simple light microscope. The immunostained sections were analyzed using confocal microscope for the fibronectin expression level. The main outcome measure was demonstration of histological changes of sclera in nanophthalmic eyes undergoing cataract surgery. Light microscopic features of nanophthalmos revealed thick fibers with fraying and lightly stained cores, irregular serrated edges, and randomly interspersed fibroblasts compared to regular arrangement of collagen fibers seen in cadaver controls. Immunohistochemistry analysis with anti-fibronectin antibody showed strong positivity in clustered fibers in nanophthalmos, and less intense diffuse staining in cadaver tissue. Histoclinical correlation was observed in one nanophthalmic scleral tissue with axial length less than 17 mm showing severe disorganization with diffuse collagenization, loss of fibrillary architecture compared to another specimen with axial length more than 17 mm. Simple, cost-effective light microscopy using basic stains was effective in identifying the characteristic histopathological features in nanophthalmic eyes, and this was further highlighted by immunohistochemistry and immunofluorescence analyses.

Nanosuspension-loaded dissolving bilayer microneedles for hydrophobic drug delivery to the posterior segment of the eye.

Intravitreal injections (IVT) are regarded as the gold standard for effective delivery of hydrophobic drugs to the back of the eye. However, as a highly invasive procedure, the injection itself may lead to poor patient compliance and severe complications. In this research work, a hybrid system of nanosuspensions (NS) and dissolving microneedles (MNs) was developed as an alternative to conventional hypodermic needles used in IVT for minimally invasive transscleral delivery of hydrophobic drugs. NS of a hydrophobic drug, triamcinolone acetonide (TA), were fabricated using a wet milling technique. TA NS optimised by central composite factorial design had a proven diameter of 246.65±8.55nm. After optimisation, TA NS were incorporated into MN arrays to form a bilayer structure by high-speed centrifugation. TA NS-loaded MNs were robust enough to pierce excised porcine sclera with insertion depth higher than 80% of the needle height and showed rapid dissolution (<3min). In contrast, the plain TA-loaded MNs exhibited poor mechanical and insertion performances and took more than 8min to be fully dissolved in the scleral tissue. Importantly, transscleral deposition studies showed that 56.46±7.76μg/mm2 of TA was deposited into the sclera after 5min of NS-loaded MN application, which was 4.5-fold higher than plain drug-loaded MNs (12.56±2.59μg/mm2). An ex vivo distribution study revealed that MN arrays could promote the transscleral penetration of hydrophobic molecules with higher drug concentrations observed in the deep layer of the sclera. Moreover, the developed TA NS-loaded MN array was biocompatible with ocular tissues, as demonstrated using the hens egg-chorioallantoic membrane assay and cytotoxicity test. The results presented here demonstrate that the hybrid system of NS and dissolving MNs can provide a novel and promising technology to alleviate retinal diseases in a therapeutically effective and minimally invasive manner.

The choroid-sclera interface: An ultrastructural study

Emmetropization is an active and visually guided process that involves the retina, choroid and sclera, and results in compensatory changes in eye growth. This guided growth is the result of visual cues and possibly mechanical interactions being translated into growth signals via molecular events from the retina into the choroid and sclera, through the choroidal scleral transition zone. If mechanical interactions were a part of the choroid-sclera signaling transduction cascade, specific morphological arrangements should be detectable in this region at the ultrastructural level. The goal of this study was to investigate the ultrastructural features of the choroidal scleral transition zone by comparing avian, non-human primate and human eyes, with the goal to confirm whether specific mechanical structures are present. Choroidal and scleral tissue from chicken, marmoset, and human eyes were imaged using transmission electron microscopy to document the choroid-sclera transition zone. In chicken eyes, fibroblast lamellae bordered the scleral matrix and formed thin end elongated processes that were undercut by scleral collagen fibrils. These processes back-looped into the scleral matrix, and displayed small club-like membrane protrusions. Differences in these arrangements in mature vs young chickens were not detected. The club-like membrane protrusions identified in chickens were rare in marmoset eyes, which instead exhibited two types of collagen fibrils discriminated by size, and were absent in the human eyes investigated. In marmoset and human eyes, elastic components were detected in the transition zone that were absent in chickens. In summary, cellular/membrane specializations indicating a mechanical interaction at the choroid-sclera transition zone were not detected in chicken, non-human primate or human eyes. If mechanotransduction is necessary for scleral growth, matrix integrity or development, alternative structural arrangements might be required.

Safety Evaluation of Photoacoustic Tomography System for Intraocular Tumors.

PurposePhotoacoustic tomography (PAT) has demonstrated the ability to characterize molecular components and architectural heterogeneities of intraocular tumors in enucleated human globes and in animals in vivo. Although laser safety levels have been established for illumination through the cornea, the safety limit for PAT illumination through the sclera has not been investigated. The purpose of this study is to examine if the energy level used in intraocular PAT results in ocular damage.MethodsRabbit eyes were exposed to pulsed laser illumination at 20 mJ/cm2 at the scleral surface. Eyes were examined at 1, 7, and 28 days after the laser exposure. Examination procedures included white light and fluorescence fundus imaging, optical coherence tomography (OCT), electroretinography (ERG), and histology with hematoxylin and eosin (H&E) staining as well as terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL staining).ResultsFundus imaging and OCT of rabbit eyes at 1, 7, and 28 days following exposure of the laser illumination of the PAT system did not reveal any damage to the retinal structures. ERG showed no significant difference between the experimental and control eyes. Similarly, H&E histology did not show abnormalities in either the scleral tissue where the laser illumination was delivered or in the retinal layers. No sign of apoptosis in the layers of the retina, choroid, or optic nerve was found on TUNEL staining.ConclusionsSimilar to the application of PAT to other organs, the proposed laser illumination energy level at 20 mJ/cm2 does not impose detectable harm to the ocular tissue.Translational RelevanceThis study addresses illumination safety issues for PAT.

Design and Investigation of Optimal Dissolving Polymeric Microneedles for Ocular Application by Using Three-Level Factorial Design

Dissolving microneedles (dis-MNs) are very attractive micro-scale technology and a minimally invasive method to be used as a tool for transdermal delivery, leading to increased bioavailability of drugs bypassing ocular tissue barrier and painless treatment method. This study aims to design and investigate the optimal dis-MNs as a potential device for ocular application using a three-level factorial design. The dis-MNs were fabricated by micromolding technique using chitosan and polyvinyl alcohol (PVA) polymer. The physical appearance of dis-MNs was observed under a digital microscope. The mechanical strength (resistance force and insertion force) was tested with a texture analyzer. The penetration depth and dissolution time at a predetermined time were tested on porcine ocular tissue. The data illustrated that the optimal dis-MNs formulation was 3%chitosan and 20%PVA in 20%PVA in a weight ratio of 1:4. The physical appearance showed pyramidal microneedles with an average 609.01±1.01 µm in height and 200.21+3.57 μm in base width. The optimal dis-MNs showed a resistance force of 40.14±2.10 N. The insertion force into the cornea tissue (1.78 N/225 arrays) was higher than sclera tissue (0.95 N/225 arrays), indicating that the optimal dis-MNs could create micro-channels on both cornea and sclera tissues. The dissolution study showed that the optimal dis-MNs formulation was completely dissolved on cornea tissue (1 min) faster than sclera tissue (3 min). In conclusion, the optimal dis-MNs presented suitable dis-MNs properties with minimally invasive device for ocular tissue, acting as an appropriate dis-MNs model for the ophthalmic drug delivery system.

Biaxial Estimation of Biomechanical Constitutive Parameters of Passive Porcine Sclera Soft Tissue

This study assesses the modelling capabilities of four constitutive hyperelastic material models to fit the experimental data of the porcine sclera soft tissue. It further estimates the material parameters and discusses their applicability to a finite element model by examining the statistical dispersion measured through the standard deviation. Fifteen sclera tissues were harvested from porcine' slaughtered at an abattoir and were subjected to equi-biaxial testing. The results show that all the four material models yielded very good correlations at correlations above 96%. The polynomial (anisotropic) model gave the best correlation of 98%. However, the estimated material parameters varied widely from one test to another such that there would be need to normalise the test data to avoid long optimisation processes after applying the average material parameters to finite element models. However, for application of the estimated material parameters to finite element models, there would be need to consider normalising the test data to reduce the search region for the optimisation algorithms. Although the polynomial (anisotropic) model yielded the best correlation, it was found that the Choi-Vito had the least variation in the estimated material parameters, thereby making it an easier option for application of its material parameters to a finite element model and requiring minimum effort in the optimisation procedure. For the porcine sclera tissue, it was found that the anisotropy was more influenced by the fiber-related properties than the background material matrix-related properties.

Corneal transparency and scleral opacity arises from the nanoarchitecture of the constituent collagen fibrils.

While human scleral and corneal tissues possess similar structural morphology of long parallel cylindrical collagen fibrils, their optical characteristics are markedly different. Using pseudospectral time-domain (PSTD) simulations of Maxwell's equations, we model light propagation through realistic representations of scleral and corneal nanoarchitecture and analyze the transmittance and spatial correlation in the near field. Our simulation results provide differing predictions for scleral opacity and corneal transparency across the vacuum ultraviolet to the mid-infrared spectral region in agreement with experimental data. The simulations reveal that the differences in optical transparency between these tissues arise through differences in light scattering emanating from the specific nanoscale arrangement and polydispersity of the constituent collagen fibrils.

Experimental and numerical analysis of electroactive characteristics of scleral tissue

The sclera provides mechanical support to retina and protects internal contents of the eye against external injuries. The scleral extracellular matrix is mainly composed of collagen fibers and proteoglycans (PGs). At physiological pH, collagen molecules are neutral but PGs contain negatively charged glycosaminoglycan chains. Thus, the sclera can be considered as a polyelectrolyte hydrogel and is expected to exhibit mechanical response when subjected to electrical stimulations. In this study, we mounted scleral strips, dissected from the posterior part of porcine eyes, at the center of a custom-designed container between two electrodes. The container was filled with NaCl solution and the bending deformation of scleral strips as a function of the applied electric voltage was measured experimentally. It was found that scleral strips reached to an average bending angle of 3°, 10° and 23° when subjected to 5V, 10V, and 15V, respectively. We also created a chemo-electro-mechanical finite element model for simulating the experimental measurements by solving coupled Poisson-Nernst-Plank and equilibrium mechanical field equations. The scleral fixed charge density and modulus of elasticity were found by fitting the experimental data. The ion concentration distribution inside the domain was found numerically and was used to explain the underlying mechanisms for the scleral electroactive response. The numerical simulations were also used to investigate the effects of various parameters such as the electric voltage and fixed charge density on the scleral deformation under an electric field. Statement of significanceThis manuscript investigates the electroactive response of scleral tissue. It demonstrates that the sclera deforms mechanically when subjected to electrical stimulations. A chemo-electro-mechanical model is also presented in order to numerically capture the electromechanical response of the sclera. This numerical model is used to explain the experimental observations by finding the ion distribution inside the tissue under an electric field. This work is significant because it shows that the sclera is an electroactive polyanionic hydrogel and it provides new information about the underlying mechanisms governing its mechanical and electrical properties.

Expression of SCO1 and SCO2 after form-deprivation myopia in Guinea pigs.

The retina is a highly energy-consuming tissue associated with visual development, and the reduced quality of retinal imaging can be related to myopia. Synthesis of cytochrome c oxidase 1 (SCO1) and synthesis of cytochrome c oxidase 2 (SCO2) are involved in ATP (adenosine triphosphate) synthesis and energy metabolism. This study aimed to observe the morphologic changes and investigate the expression of SCO1 and SCO2 induced by form-deprivation myopia (FDM) in the retina and sclera of guinea pigs. Thirty-six 3-week-old male guinea pigs were randomly assigned to one of two groups: (1) the model group (n = 18), in which the right eyes were covered by a thin opaque balloon as FDM group, and the left eyes were uncovered and served as the contralateral control group; (2) the blank control group (n = 18), in which bilateral eye received no manipulation. Eyeballs were enucleated for histological analysis. The retina and sclera of the guinea pigs were separated to determine the protein and mRNA expression levels of SCO1 and SCO2, respectively. After four weeks of form deprivation (FD), the refractive degree and axial length increased significantly (P < 0.001). The retinal and scleral tissues were moderately thinner, and the ganglion cells and the cells of inner and outer nuclear layers in the retina became fewer. Compared with the contralateral control group (P < 0.001) and the blank control group (P < 0.001), the collagen content of the sclera became less in the FDM group. The protein and mRNA expression levels of SCO1 and SCO2 in the FDM group were significantly lower than those in the contralateral control group and the blank control group (P < 0.05). The morphologies of the retina and sclera were changed, and the expression of SCO1 and SCO2 at the protein and transcription levels was significantly reduced in the FDM group. Given these changes, SCO1 and SCO2 genes may be involved in myopic progression.

Finite element analysis of the effect of local posterior sclera collagen cross-linking on eyeball shape

China is the country with high incidence of high myopia in the world. High myopia can cause severe vision impairment. So far, there is no effective treatment for high myopia in clinic. Scleral collagen cross-linking surgery has been proven to be effective in preventing animal eye axial elongation in vitro and in vivo. However, the influence of posterior scleral collagen cross-linking on the deformation of the whole eyeball is still unclear. In this study, finite element simulation were used to analyze the changes of eyeball shape and the position of light casting on the retina after posterior sclera cross-linking, and the mathematical algorithm was written to verify their similarity. The results showed that the shape of the whole eyeball was still very similar before and after cross-linking, and the diopter of the eyeball after cross-linking had little change, which had almost no effect on the position of light projection on the retina. Our results indicate that posterior sclera cross-linking wouldn't lead to distortion to the optometry, that is, the increase of elastic modulus in local scleral tissue after cross-linking wouldn't cause new problem of optometry and vision.

Usage of E-Polytetrafluoroethylene (e-PTFE) Membrane for Managing Trabeculectomy Flap- Related Over-Filtration Due to Unavailability of Scleral Patch Graft during Nation-Wide Lockdown

Scleral flap tears during trabeculectomy are difficult to repair in a predictable fashion. Donor scleral flap reinforcements are commonly preferred for managing trabeculectomy flap-related over-filtration, leading to shallow anterior chamber (AC). Due to the advent of COVID-19 lockdown, especially in the initial phases, eye banking activities almost came to a standstill, with almost no corneal and/or scleral tissue retrievals. Hence, in this manuscript we have presented a mini case series with follow-up of two of our cases; where Gore-Tex (e-polytetrafluoroethylene) implant was used as an alternative to scleral patch graft, for managing trabeculectomy flap-related over-filtration, with their pros and cons. Though Gore-Tex implant stability in both cases were contentious, it still served the purpose of managing the flap-related over- filtration and subsequent shallow AC.

Neuro-Ophthalmological Optic Nerve Cupping: An Overview

Optic nerve cupping or enlargement of the cup-to-disc ratio is widely recognized as a feature of glaucoma, however it may also occur in non-glaucomatous optic neuropathies. The most well-recognized non-glaucomatous optic neuropathies that cause cupping include compressive optic neuropathies, arteritic anterior ischemic optic neuropathies, hereditary optic neuropathies, and optic neuritis. Cupping is thought to consist of two main components: prelaminar and laminar thinning. The former is a shallow form of cupping and related to loss of retinal ganglion cells, whereas the latter involves damage to the lamina cribrosa and peripapillary scleral connective tissue. Differentiating glaucomatous and non-glaucomatous optic nerve cupping remains challenging even for experienced observers. Classically, the optic nerve in non-glaucomatous causes has pallor of the neuroretinal rim, but the optic nerve should not be examined in isolation. The patient’s medical history, history of presenting illness, visual function (visual acuity, color vision and visual field testing) and ocular examination also need to be considered. Ancillary testing such as optical coherence tomography of the retinal nerve fiber layer and ganglion cell layer-inner plexiform layer may also be helpful in localizing the disease. In this review, we review the non-glaucomatous causes of cupping and provide an approach to evaluating a patient that presents with an enlarged cup-to-disc ratio.