Influence of Permeant Lipophilicity on Permeation Across Human Sclera
Wen, He; Li, S. Kevin
2010-01-01
Purpose The objectives of this study were to determine the effects of permeant lipophilicity on permeant uptake into and transport across human sclera for transscleral delivery. Methods Model permeants with a wide range of lipophilicities were selected and studied with human sclera. Uptake experiments were carried out to measure permeant partitioning into the sclera. Transport experiments were performed in side-by-side diffusion cells, and the permeability coefficients and transport lag times of the permeants across the sclera were evaluated. Results Permeants with higher lipophilicity showed higher partition coefficients to human sclera, and the apparent transport lag time also increased significantly as the permeant lipophilicity increased. No correlation between the permeability coefficients and lipophilicity of the model permeants was observed in this study with human sclera. A hypothesis on the different findings between the present and previous studies was proposed. Conclusions Permeants with higher lipophilicity exhibited stronger binding to human sclera and would therefore lead to larger permeant partitioning to the sclera and longer transport lag time. The steady-state permeability coefficients of the permeants were not significantly affected by permeant lipophilicity. PMID:20734114
Ferrari, G.; Quarta, M.; Macaluso, C.; Govoni, P.; Dallatana, D.; Santi, P.
2009-01-01
Purpose To evaluate porcine sclera as a model of human sclera for in vitro studies of transscleral drug delivery of both low and high molecular weight compounds. Methods Human and porcine scleras were characterized for thickness and water content. The tissue surface was examined by scanning electron microscopy (SEM), and the histology was studied with hematoxylin-eosin staining. Comparative permeation experiments were performed using three model molecules, acetaminophen as the model compound for small molecules; a linear dextran with a molecular weight of 120 kDa as the model compound for high molecular weight drugs; and insulin, which was chosen as the model protein. Permeation parameters such as flux, lag time, and permeability coefficient were determined and compared. Results Human and porcine scleras have a similar histology and collagen bundle organization. The water content is approx 70% for both tissues while a statistically significant difference was found for the thickness, porcine sclera being approximately twofold thicker than human sclera. Differences in thickness produced differences in the permeability coefficient. In fact, human sclera was found to be two to threefold more permeable toward the three molecules studied than porcine sclera. Conclusions The results obtained in the present paper prove that porcine sclera can be considered a good model for human sclera for in vitro permeation experiments of both low and high molecular weight compounds. In fact, if the different tissue thickness is taken into account, comparable permeability was demonstrated. This suggests a possible use of this model in the evaluation of the transscleral permeation of new biotech compounds, which currently represent the most innovative and efficient therapeutic options for the treatment of ocular diseases. PMID:19190734
Nicoli, S; Ferrari, G; Quarta, M; Macaluso, C; Govoni, P; Dallatana, D; Santi, P
2009-01-01
To evaluate porcine sclera as a model of human sclera for in vitro studies of transscleral drug delivery of both low and high molecular weight compounds. Human and porcine scleras were characterized for thickness and water content. The tissue surface was examined by scanning electron microscopy (SEM), and the histology was studied with hematoxylin-eosin staining. Comparative permeation experiments were performed using three model molecules, acetaminophen as the model compound for small molecules; a linear dextran with a molecular weight of 120 kDa as the model compound for high molecular weight drugs; and insulin, which was chosen as the model protein. Permeation parameters such as flux, lag time, and permeability coefficient were determined and compared. Human and porcine scleras have a similar histology and collagen bundle organization. The water content is approx 70% for both tissues while a statistically significant difference was found for the thickness, porcine sclera being approximately twofold thicker than human sclera. Differences in thickness produced differences in the permeability coefficient. In fact, human sclera was found to be two to threefold more permeable toward the three molecules studied than porcine sclera. The results obtained in the present paper prove that porcine sclera can be considered a good model for human sclera for in vitro permeation experiments of both low and high molecular weight compounds. In fact, if the different tissue thickness is taken into account, comparable permeability was demonstrated. This suggests a possible use of this model in the evaluation of the transscleral permeation of new biotech compounds, which currently represent the most innovative and efficient therapeutic options for the treatment of ocular diseases.
Mayhew, Jessica A; Gómez, Juan-Carlos
2015-08-01
Human eye morphology is considered unique among the primates in that humans possess larger width/height ratios (WHR), expose a greater amount of visible sclera (SSI; width of exposed eyeball/width of visible iris), and critically, have a white sclera due to a lack of pigmentation. White sclera in humans amplifies gaze direction, whereas the all-dark eyes of apes are hypothesized to conceal gaze from others. This study examines WHR and SSI in humans (N = 13) and gorillas (N = 85) engaged in direct and averted gazes and introduces a qualitative assessment of sclera color to evaluate variations in sclera pigmentation. The results confirm previous findings that humans possess a larger WHR than gorillas but indicate that humans and gorillas display similar amounts of visible sclera. Additionally, 72% (N = 124) of gorilla eyes in this sample deviated from the assumed all-dark eye condition. This questions whether gaze camouflage is the primary function of darkened sclera in non-human primates or whether other functional roles can be ascribed to the sclera, light or dark. We argue that white sclera evolved to amplify direct gazes in humans, which would have played a significant role in the development of ostensive communication, which is communication that both shows something and shows the intention to show something. We conclude that the horizontal elongation of the human eye, rather than sclera color, more reliably distinguishes human from great ape eyes, represented here by gorillas. © 2015 Wiley Periodicals, Inc.
Seko, Yuko; Azuma, Noriyuki; Yokoi, Tadashi; Kami, Daisuke; Ishii, Ryuga; Nishina, Sachiko; Toyoda, Masashi; Shimokawa, Hitoyata; Umezawa, Akihiro
2017-01-01
Purpose/Aim: We sought to identify the anteroposterior spatial gene expression hierarchy in the human sclera to develop a hypothesis for axial elongation and deformity of the eyeball. We analyzed the global gene expression of human scleral cells derived from distinct parts of the human infant sclera obtained from surgically enucleated eyes with retinoblastoma, using Affymetrix GeneChip oligonucleotide arrays, and compared, in particular, gene expression levels between the anterior and posterior parts of the sclera. The ages of three donors were 10M, 4M, and 1Y9M. K-means clustering analysis of gene expression revealed that expression levels of cartilage-associated genes such as COLXIA and ACAN increased from the anterior to the posterior part of the sclera. Microarray analyses and RT-PCR data showed that the expression levels of MGP, COLXIA, BMP4, and RARB were significantly higher in the posterior than in the anterior sclera of two independent infant eyes. Conversely, expression levels of WNT2, DKK2, GREM1, and HOXB2 were significantly higher in the anterior sclera. Among several Wnt-family genes examined, WNT2B was found to be expressed at a significantly higher level in the posterior sclera, and the reverse order was observed for WNT2. The results of luciferase reporter assays suggested that a GSK-3β inhibitor stimulated Wnt/β-catenin signaling particularly strongly in the posterior sclera. The expression pattern of RARB, a myopia-related gene, was similar in three independent eyes. Chondrogenic potential was higher and Wnt/β-catenin signaling was more potently activated by a GSK-3β inhibitor in the posterior than in the anterior part of the human infant sclera. Although the differences in the gene expression profiles between the anterior and posterior sclera might be involved only in normal growth processes, this anteroposterior hierarchy in the sclera might contribute to disorders involving abnormal elongation and deformity of the eyeball, including myopia.
Park, Seung Hyun; Lee, Kang Ju; Lee, JiYong; Yoon, Jae Hyoung; Jo, Dong Hyun; Kim, Jeong Hun; Kang, Keonwook; Ryu, WonHyoung
2016-10-15
The sclera provides the structural support of the eye and protects the intraocular contents. Since it covers a large portion of the eye surface and has relatively high permeability for most drugs, the sclera has been used as a major pathway for drug administration. Recently, microneedle (MN) technology has shown the possibility of highly local and minimally-invasive drug delivery to the eye by MN insertion through the sclera or the suprachoroidal space. Although ocular MN needs to be inserted through the sclera, there has been no systematic study to understand the mechanical properties of the sclera, which are important to design ocular MNs. In this study, we investigated a MN-based method to measure the puncture resistance and fracture toughness of the sclera. To reflect the conditions of MN insertion into the sclera, force-displacement curves obtained from MN-insertion tests were used to estimate the puncture resistance and fracture toughness of sclera tissue. To understand the effect of the insertion conditions, dependency of the mechanical properties on insertion speeds, pre-strain of the sclera, and MN sizes were analyzed and discussed. Measurement of mechanical property of soft biological tissue is challenging due to variations between tissue samples or lack of well-defined measurement techniques. Although non-invasive measurement techniques such as nano/micro indentation were employed to locally measure the elastic modulus of soft biological materials, mechanical properties such as puncture resistance or fracture toughness, which requires "invasive" measurement and is important for the application of "microneedles or hypodermic needles", has not been well studied. In this work, we report minimally-invasive measurement of puncture resistance and fracture toughness of sclera using a double MN insertion method. Parametric studies showed that use of MN proved to be advantageous because of minimally-invasive insertion into tissue as well as higher sensitivity to sub-tissue architecture during the measurement. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
... clear front section of the eye) to the optic nerve at the back of the eye. The sclera gives the eyeball its white color. The cornea and sclera are made of the same type of collagen fibers. In the cornea, the fibers are arranged in ...
Scleral anisotropy and its effects on the mechanical response of the optic nerve head
Coudrillier, Baptiste; Boote, Craig; Quigley, Harry A.
2012-01-01
This paper presents a computational modeling study of the effects of the collagen fiber structure on the mechanical response of the sclera and the adjacent optic nerve head (ONH). A specimen-specific inverse finite element method was developed to determine the material properties of two human sclera subjected to full-field inflation experiments. A distributed fiber model was applied to describe the anisotropic elastic behavior of the sclera. The model directly incorporated wide angle x-ray scattering measurements of the anisotropic collagen structure. The converged solution of the inverse method was used in micromechanical studies of the mechanical anisotropy of the sclera at different scales. The effects of the scleral collagen fiber structure on the ONH deformation were evaluated by progressively filtering out local anisotropic features. It was found that the majority of the midposterior sclera could be described as isotropic without significantly affecting the mechanical response of the tissues of the ONH. In contrast, removing local anisotropic features in the peripapillary sclera produced significant changes in scleral canal expansion, and lamina cribrosa deformation. Local variations in the collagen structure of the peripapillary sclera significantly influenced the mechanical response of the ONH. PMID:23188256
Simulation analysis of the transparency of cornea and sclera
NASA Astrophysics Data System (ADS)
Yang, Chih-Yao; Tseng, Snow H.
2017-02-01
Both consist of collagen fibrils, sclera is opaque whereas cornea is transparent for optical wavelengths. By employing the pseudospectral time-domain (PSTD) simulation technique, we model light impinging upon cornea and sclera, respectively. To analyze the scattering characteristics of light, the cornea and sclera are modeled by different sizes and arrangements of the non-absorbing collagen fibrils. Various factors are analyzed, including the wavelength of incident light, the thickness of the scattering media, position of the collagen fibrils, size distribution of the fibrils.
Intrascleral Drug Delivery to the Eye Using Hollow Microneedles
Jiang, Jason; Moore, Jason S.; Edelhauser, Henry F.; Prausnitz, Mark R.
2010-01-01
Purpose This study tested the hypothesis that hollow microneedles can infuse solutions containing soluble molecules, nanoparticles, and microparticles into sclera in a minimally invasive manner. Methods Individual hollow microneedles were inserted into, but not across, human cadaver sclera and aqueous solutions containing sulforhodamine or fluorescently-tagged nanoparticles or microparticles were infused into sclera at constant pressure. The infused volume of fluid was measured and imaged histologically as a function of scleral thickness, infusion pressure, needle retraction depth and the presence of spreading enzymes (hyaluronidase and collagenase). Results Individual hollow microneedles were able to insert into sclera. Fluid infusion was extremely slow after microneedle insertion into the sclera without retraction, but partial retraction of the microneedle over a distance of 200–300 μm enabled infusion of 10–35 μl of fluid into the tissue. Scleral thickness and infusion pressure had insignificant effects on fluid delivery. Nanoparticle suspensions were also delivered into sclera, but microparticles were delivered only in the presence of hyaluronidase and collagenase spreading enzymes, which suggested the role of scleral glycosaminoglycans and collagen fibers as rate-limiting barriers. Conclusion This study shows that hollow microneedles can infuse solutions into the sclera for minimally invasive delivery of soluble molecules, nanoparticles and microparticles. PMID:18979189
Zaman, Raiyan T; Rajaram, Narasimhan; Nichols, Brandon S; Rylander, Henry G; Wang, Tianyi; Tunnell, James W; Welch, Ashley J
2011-07-01
Light scattering in the normally white sclera prevents diagnostic imaging or delivery of a focused laser beam to a target in the underlying choroid layer. In this study, we examine optical clearing of the sclera and changes in blood flow resulting from the application of glycerol to the sclera of rabbits. Recovery dynamics are monitored after the application of saline. The speed of clearing for injection delivery is compared to the direct application of glycerol through an incision in the conjunctiva. Although, the same volume of glycerol was applied, the sclera cleared much faster (5 to 10 s) with the topical application of glycerol compared to the injection method (3 min). In addition, the direct topical application of glycerol spreads over a larger area in the sclera than the latter method. A diffuse optical spectroscopy system provided spectral analysis of the remitted light every two minutes during clearing and rehydration. Comparison of measurements to those obtained from phantoms with various absorption and scattering properties provided estimates of the absorption coefficient and reduced scattering coefficient of rabbit eye tissue.
Nanoscale characterization of the biomechanical properties of collagen fibrils in the sclera
DOE Office of Scientific and Technical Information (OSTI.GOV)
Papi, M.; Paoletti, P.; Geraghty, B.
We apply the PeakForce Quantitative Nanomechanical Property Mapping (PFQNM) atomic force microscopy mode for the investigation of regional variations in the nanomechanical properties of porcine sclera. We examine variations in the collagen fibril diameter, adhesion, elastic modulus and dissipation in the posterior, equatorial and anterior regions of the sclera. The mean fibril diameter, elastic modulus and dissipation increased from the posterior to the anterior region. Collagen fibril diameter correlated linearly with elastic modulus. Our data matches the known macroscopic mechanical behavior of the sclera. We propose that PFQNM has significant potential in ocular biomechanics and biophysics research.
Perilimbal sclera mechanical properties: Impact on intraocular pressure in porcine eyes
Man, Xiaofei; Arroyo, Elizabeth; Dunbar, Martha; Reed, David M.; Shah, Neil; Kagemann, Larry; Kim, Wonsuk; Moroi, Sayoko E.
2018-01-01
There is extensive knowledge on the relationship of posterior scleral biomechanics and intraocular pressure (IOP) load on glaucomatous optic neuropathy; however, the role for biomechanical influence of the perilimbal scleral tissue on the aqueous humor drainage pathway, including the distal venous outflow system, and IOP regulation is not fully understood. The purpose of this work is to study the outflow characteristics of perfused porcine eyes relative to the biomechanical properties of the perilimbal sclera, the posterior sclera and the cornea. Enucleated porcine eyes from eleven different animals were perfused with surrogate aqueous at two fixed flow rates while monitoring their IOP. After perfusion, mechanical stress-strain and relaxation tests were conducted on specimens of perilimbal sclera, posterior sclera, and cornea from the same perfused eyes. Statistical analysis of the data demonstrated a strong correlation between increased tangent modulus of the perilimbal sclera tissues and increased perfusion IOP (R2 = 0.74, p = 0.0006 at lower flow rate and R2 = 0.71, p = 0.0011 at higher flow rate). In contrast, there were no significant correlations between IOP and the tangent modulus of the other tissues (Posterior sclera: R2 = 0.17 at lower flow rate and R2 = 0.30 at higher flow rate; cornea: R2 = 0.02 at lower flow rate and R2<0.01 at higher flow rate) nor the viscoelastic properties of any tissue (R2 ≤ 0.08 in all cases). Additionally, the correlation occurred for IOP and not net outflow facility (R2 ≤ 0.12 in all cases). These results provide new evidence that IOP in perfused porcine eyes is strongly influenced by the tangent modulus, sometimes called the tissue stiffness, of the most anterior portion of the sclera, i.e. the limbus. PMID:29718942
NASA Astrophysics Data System (ADS)
Baum, Olga; Wachsmann-Hogiu, Sebastian; Sobol, Emil
2018-02-01
Thermo-mechanical effect of laser radiation is a basis of new method of normalization of intraocular pressure in glaucomatous eyes due to laser-assisted pore formation in eye sclera. Laser-induced creation of pores in sclera increases hydraulic permeability. Stability of laser-induced pore system is achieved via gas nano-bubbles arisen in the sclera under laser radiation as a result of temperature dependency of gas solubility. The stabilization of laser-induced gas and pore systems in the tissue is an important mechanism for a long lasting healing of glaucoma observed in clinical trials with one year follow-up.
Coudrillier, Baptiste; Tian, Jing; Alexander, Stephen; Myers, Kristin M.; Quigley, Harry A.; Nguyen, Thao D.
2012-01-01
Purpose. The objective of this study was to measure the biomechanical response of the human posterior sclera in vitro and to estimate the effects of age and glaucoma. Methods. Scleral specimens from 22 donors with no history of glaucoma and 11 donors with a history of glaucoma were excised 3 mm posterior to the equator and affixed to an inflation chamber. Optic nerve cross-sections were graded to determine the presence of axon loss. The time-dependent inflation response was measured in a series of pressure-controlled load–unload tests to 30 mm Hg and creep tests to 15 and 30 mm Hg. Circumferential and meridional strains were computed from the digital image correlation displacements, and midposterior stresses were determined from pressure and deformed geometry. Results. Among normal specimens, older age was predictive of a stiffer response and a thinner sclera. In the age group 75 to 93, diagnosed glaucoma eyes with axon damage were thicker than normal eyes. Both damaged and undamaged glaucoma eyes had a different strain response in the peripapillary sclera characterized by a stiffer meridional response. Undamaged glaucoma eyes had slower circumferential creep rates in the peripapillary sclera than normal eyes. Glaucoma eyes were not different from normal eyes in stresses and strains in the midposterior sclera. Conclusions. The observed differences in the biomechanical response of normal and glaucoma sclera may represent baseline properties that contribute to axon damage, or may be characteristics that result from glaucomatous disease. PMID:22395883
Park, Choul Yong; Marando, Catherine M; Liao, Jason A; Lee, Jimmy K; Kwon, Jiwon; Chuck, Roy S
2016-10-01
To investigate the architecture and distribution of collagen and elastin in human limbal conjunctiva, Tenon's capsule, and sclera. The limbal conjunctiva, Tenon's capsule, and sclera of human donor corneal buttons were imaged with an inverted two-photon excited fluorescence microscope. No fixation process was necessary. The laser (Ti:sapphire) was tuned at 850 nm for two-photon excitation. Backscatter signals of second harmonic generation (SHG) and autofluorescence (AF) were collected through a 425/30-nm and a 525/45-nm emission filter, respectively. Multiple, consecutive, and overlapping (z-stack) images were acquired. Collagen signals were collected with SHG, whereas elastin signals were collected with AF. The size and density of collagen bundles varied widely depending on depth: increasing from conjunctiva to sclera. In superficial image planes, collagen bundles were <10 μm in width, in a loose, disorganized arrangement. In deeper image planes (episclera and superficial sclera), collagen bundles were thicker (near 100 μm in width) and densely packed. Comparatively, elastin fibers were thinner and sparse. The orientation of elastin fibers was independent of collagen fibers in superficial layers; but in deep sclera, elastin fibers wove through collagen interbundle gaps. At the limbus, both collagen and elastin fibers were relatively compact and were distributed perpendicular to the limbal annulus. Two-photon excited fluorescence microscopy has enabled us to understand in greater detail the collagen and elastin architecture of the human limbal conjunctiva, Tenon's capsule, and sclera.
Hisatomi, Toshio; Sonoda, Koh‐hei; Ishikawa, Fumihiko; Qiao, Hong; Nakamura, Takahiro; Fukata, Mitsuhiro; Nakazawa, Toru; Noda, Kousuke; Miyahara, Shinsuke; Harada, Mine; Kinoshita, Shigeru; Hafezi‐Moghadam, Ali; Ishibashi, Tatsuro; Miller, Joan W
2007-01-01
Aims To characterise bone marrow derived cells in the sclera under normal and inflammatory conditions, we examined their differentiation after transplantation from two different sources, bone marrow and haematopoietic stem cells (HSC). Methods Bone marrow and HSC from green fluorescent protein (GFP) transgenic mice were transplanted into irradiated wild‐type mice. At 1 month after transplantation, mice were sacrificed and their sclera examined by histology, immunohistochemistry (CD11b, CD11c, CD45), and transmission and scanning electron microscopy. To investigate bone marrow derived cell recruitment under inflammatory conditions, experimental autoimmune uveitis (EAU) was induced in transplanted mice. Results GFP positive cells were distributed in the entire sclera and comprised 22.4 (2.8)% (bone marrow) and 28.4 (10.9)% (HSC) of the total cells in the limbal zone and 18.1 (6.7)% (bone marrow) and 26.3 (3.4)% (HSC) in the peripapillary zone. Immunohistochemistry showed that GFP (+) CD11c (+), GFP (+) CD11b (+) cells migrated in the sclera after bone marrow and HSC transplantation. Transmission and scanning electron microscopy revealed antigen presenting cells among the scleral fibroblasts. In EAU mice, vast infiltration of GFP (+) cells developed into the sclera. Conclusion We have provided direct and novel evidence for the migration of bone marrow and HSC cells into the sclera differentiating into macrophages and dendritic cells. Vast infiltration of bone marrow and HSC cells was found to be part of the inflammatory process in EAU. PMID:17035278
Iontophoretic transport of charged macromolecules across human sclera.
Chopra, Poonam; Hao, Jinsong; Li, S Kevin
2010-03-30
The mechanisms of transscleral iontophoresis have been investigated previously with small molecules in rabbit sclera. The objective of the present study was to examine transscleral iontophoretic transport of charged macromolecules across excised human sclera. Passive and 2mA iontophoretic transport experiments were conducted in side-by-side diffusion cells with human sclera. The effects of iontophoresis upon transscleral transport of model permeants bovine serum albumin (BSA) and polystyrene sulfonic acid (PSS) as well as a model drug bevacizumab (BEV) were determined. Passive and iontophoretic transport experiments of tetraethylammonium (TEA) and salicylic acid (SA) and passive transport experiments of the macromolecules served as the controls. The results of iontophoresis enhanced transport of TEA and SA across human sclera were consistent with those in a previous rabbit sclera study. For the iontophoretic transport of macromolecules BSA and BEV, higher iontophoretic fluxes were observed in anodal iontophoresis as compared to passive and cathodal iontophoresis. This suggests the importance of electroosmosis. For the polyelectrolyte PSS, higher iontophoretic flux was observed in cathodal iontophoresis compared to anodal iontophoresis. Both electroosmosis and electrophoresis affected iontophoretic fluxes of the macromolecules; the relative contributions of electroosmosis and electrophoresis were a function of molecular size and charge of the macromolecules. Copyright (c) 2009 Elsevier B.V. All rights reserved.
Holló, Gábor; Naghizadeh, Farzaneh
2013-01-01
To investigate whether the tightness of contact between the tube and the limbal sclera tunnel can be evaluated with high-magnification anterior segment optical coherence tomography (OCT) imaging following Ahmed glaucoma valve implantation. Tightness between the tube and the limbal sclera tunnel was investigated with the CAM-L cornea lens adapter of the Optovue Fourier-domain OCT (RTVue-OCT) for 21 uncomplicated Ahmed glaucoma valves implanted in 20 eyes of 19 patients with glaucoma. Nineteen valves were implanted 4 to 124 months earlier (late postoperative cases) and 2 valves 1 day prior to the imaging (early postoperative cases). All valves were introduced into the anterior chamber via a limbal sclera tunnel. The limbal intratunnel part of the tube was successfully imaged in all but 2 cases where an additional full-thickness sclera patch was used. In 14 cases, the contact was tight without tube compression. In 5 cases, the tube was partially compressed but remained open in the limbal sclera tunnel, and redilated behind the limbus. No case with loose contact or peritubular filtration was seen. The posterior run of the tube was successfully imaged in all 19 cases without a full-thickness sclera patch. High-magnification imaging with the CAM- L anterior segment adapter of the RTVue-OCT allows detailed examination of the limbal insertion area of tubes in both the early and late postoperative periods. Therefore this method may potentially be applied for detection of complications related to tube insertion after glaucoma drainage device surgery.
Scleral Biomechanics in the Aging Monkey Eye
Girard, Michaël J. A.; Suh, J-K. Francis; Bottlang, Michael; Burgoyne, Claude F.; Downs, J. Crawford
2010-01-01
Purpose To investigate the age-related differences in the inhomogeneous, anisotropic, nonlinear biomechanical properties of posterior sclera from old (22.9 ± 5.3 years) and young (1.5 ± 0.7 years) rhesus monkeys. Methods The posterior scleral shell of each eye was mounted on a custom-built pressurization apparatus, then intraocular pressure (IOP) was elevated from 5 to 45 mmHg while the 3D displacements of the scleral surface were measured using speckle interferometry. Each scleral shell geometry was digitally reconstructed from data generated by a 3D digitizer (topography) and 20 MHz ultrasounds (thickness). An inverse finite element (FE) method incorporating a fiber-reinforced constitutive model was used to extract a unique set of biomechanical properties for each eye. Displacements, thickness, stress, strain, tangent modulus, structural stiffness, and preferred collagen fiber orientation were mapped for each posterior sclera. Results The model yielded 3-D deformations of posterior sclera that matched well with those observed experimentally. The posterior sclera exhibited inhomogeneous, anisotropic, nonlinear mechanical behavior. The sclera was significantly thinner (p = 0.038), and tangent modulus and structural stiffness were significantly higher in old monkeys (p < 0.0001). On average, scleral collagen fibers were circumferentially oriented around the optic nerve head (ONH). We found no difference in the preferred collagen fiber orientation and fiber concentration factor between age groups. Conclusions Posterior sclera from old monkeys is significantly stiffer than that from young monkeys and is therefore subject to higher stresses but lower strains at all levels of IOP. Age-related stiffening of the sclera may significantly influence ONH biomechanics, and potentially contribute to age-related susceptibility to glaucomatous vision loss. PMID:19494203
Diffusion of macromolecules through sclera.
Miao, Heng; Wu, Bi-Dong; Tao, Yong; Li, Xiao-Xin
2013-02-01
To quantify the in vitro permeability coefficient over different topographical locations of porcine sclera to macromolecules with different molecular weight. Fresh equatorial and posterior superotemporal porcine sclera was mounted in a two-chamber diffusion apparatus, and its permeability to fluorescein isothiocyanate (FITC)-conjugated dextrans ranging in molecular weight from 40 kDa to 150 kDa was determined by fluorescence spectrophotometry. The sclera was processed as frozen sections and viewed with a fluorescence microscope. The thickness of the area and the thickness that macromolecules enriched in the surface of sclera were measured. The permeability coefficient (Pc) of porcine sclera to macromolecules was significantly higher (40 kDa, p = 0.028; 70 kDa, p = 0.033; 150 kDa, p = 0.007) in equatorial region than posterior, which could be attributed to the significant difference of thickness (p < 0.001, Kruskal-Wallis) between them. Moreover, linear regression indicated a significant negative relationship (40 kDa, p < 0.001; 70 kDa, p = 0.015; 150 kDa, p < 0.001) between scleral permeability coefficient and thickness. Also, Pc declined significantly with increasing molecular weight (MW, p < 0.001, Kruskal-Wallis). The area that the macromolecules enriched in the scleral surface was thicker for those with larger MW (p < 0.001, Kruskal-Wallis). The maximum MW and size for equatorial and posterior superotemporal scleral tissue were 185.01 KDa and 180.42 KDa, 9.92 nm and 9.67 nm, respectively. The permeability coefficient of porcine sclera has a significant negative relationship with scleral thickness and MW of macromolecules. Larger macromolecules are more likely to accumulate in scleral surface. The difference between topographical locations may have pharmacokinetic implications when considering transscleral diffusion of macromolecules. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.
In the presence of conflicting gaze cues, fearful expression and eye-size guide attention.
Carlson, Joshua M; Aday, Jacob
2017-10-19
Humans are social beings that often interact in multi-individual environments. As such, we are frequently confronted with nonverbal social signals, including eye-gaze direction, from multiple individuals. Yet, the factors that allow for the prioritisation of certain gaze cues over others are poorly understood. Using a modified conflicting gaze paradigm, we tested the hypothesis that fearful gaze would be favoured amongst competing gaze cues. We further hypothesised that this effect is related to the increased sclera exposure, which is characteristic of fearful expressions. Across three experiments, we found that fearful, but not happy, gaze guides observers' attention over competing non-emotional gaze. The guidance of attention by fearful gaze appears to be linked to increased sclera exposure. However, differences in sclera exposure do not prioritise competing gazes of other types. Thus, fearful gaze guides attention among competing cues and this effect is facilitated by increased sclera exposure - but increased sclera exposure per se does not guide attention. The prioritisation of fearful gaze over non-emotional gaze likely represents an adaptive means of selectively attending to survival-relevant spatial locations.
Cortexin diffusion in human eye sclera
DOE Office of Scientific and Technical Information (OSTI.GOV)
Genina, Elina A; Bashkatov, A N; Tuchin, Valerii V
2011-05-31
Investigation of the diffusion of cytamines, a typical representative of which is cortexin, is important for evaluating the drug dose, necessary to provide sufficient concentration of the preparation in the inner tissues of the eye. In the present paper, the cortexin diffusion rate in the eye sclera is measured using the methods of optical coherence tomography (OCT) and reflectance spectroscopy. The technique for determining the diffusion coefficient is based on the registration of temporal dependence of the eye sclera scattering parameters caused by partial replacement of interstitial fluid with the aqueous cortexin solution, which reduces the level of the OCTmore » signal and decreases the reflectance of the sclera. The values of the cortexin diffusion coefficient obtained using two independent optical methods are in good agreement. (optical technologies in biophysics and medicine)« less
NASA Astrophysics Data System (ADS)
Baum, Olga; Wachsmann-Hogiu, Sebastian; Milner, Thomas; Sobol, Emil
2017-06-01
Pores in sclera enhance uveoscleral water outflow and can normalize intraocular pressure in glaucomatous eyes. The aims of this study are to demonstrate laser-induced formation of pores with a dendritic structure and to answer the questions: How is a pore system stable and can laser treatment provide a long-lasting pressure stabilization effect? Effect of 1.56 µm laser radiation on porcine eye sclera was studied using atomic force microscopy and super resolution structured irradiation microscopy with fluorescent markers. Results suggest that the pores with a complex spatial configuration can arise as a result of laser irradiation and that laser-generated stable gas nanobubbles coated with calcium ions allow pore stabilization in the sclera. Our results support a laser based approach for treatment of glaucoma.
NASA Astrophysics Data System (ADS)
Singh, Manmohan; Nair, Achuth; Aglyamov, Salavat R.; Wu, Chen; Han, Zhaolong; Lafon, Ericka; Larin, Kirill V.
2017-02-01
The mechanophysiology of tissues in the posterior eye have been implicated for diseases such as myopia and glaucoma. For example, the eye-globe shape, and consequently optical axial length, can be affected by scleral stiffness. In glaucoma, an elevated intraocular pressure is the primary risk factor for glaucoma, which is the 2nd most prevalent known cause of blindness. Recent work has shown that biomechanical properties of the optic nerve are critical for the onset and progression of glaucoma because weak tissues cause large displacements in the optic nerve, causing tissue damage. In this work, we utilize air-pulse optical coherence elastography (OCE) to quantify the spatial distribution of biomechanical properties of the optic nerve, its surrounding tissues, and the posterior sclera. Air-pulse measurements were made in a grid on in situ porcine eyes in the whole eye-globe configuration as various IOPs. The OCE-measured displacement process was linked to tissue stiffness by a simple kinematic equation. The results show that the optic nerve and peripapillary sclera are much stiffer than the surrounding sclera, and the stiffness of the optic nerve and peripapillary sclera increased as a function of IOP. However, the stiffness of the surrounding sclera did not dramatically increase. Our results show that understanding the dynamics of the biomechanical properties of the eye are critical to understand the aforementioned diseases and may provide additional information for assessing visual health and integrity.
Evaluation of posterior porcine sclera elasticity in situ as a function of IOP
NASA Astrophysics Data System (ADS)
Nair, Achuth; Wu, Chen; Singh, Manmohan; Liu, Chih Hao; Raghunathan, Raksha; Nguyen, Jennifer; Goh, Megan; Aglyamov, Salavat; Larin, Kirill V.
2018-02-01
The biomechanical properties of the sclera could provide key information regarding the progression and etiology of ocular diseases. For example, an elevated intraocular pressure is one of the most common risk factors for glaucoma and can cause pathological deformations in the tissues of the posterior eye, such as the sclera, potentially damaging these vital tissues. Previous work has evaluated scleral biomechanical response to global displacements with techniques such as inflation testing. However, these methods cannot provide localized biomechanical assessments. In this pilot work, we induce low amplitude (< 10 μm) elastic waves using acoustic radiation force in posterior scleral tissue of fresh porcine eyes (n=2) in situ. The wave propagation induced using an ultrasound transducer was detected across an 8 mm region using a phase-sensitive optical coherence elastography system (PhS-OCE). The elastographic measurements were taken at various artificially controlled intraocular pressures (IOP). The IOP was pre-cycled before being set to 10 mmHg for the first measurement. Subsequent measurements were taken at 20 mmHg and 30 mmHg for each sample. The results show an increase in the stiffness of the sclera as a function of IOP. Furthermore, we observed a variation in the elasticity based on direction, suggesting that the sclera has anisotropic biomechanical properties. Our results show that OCE is an effective method for evaluating the mechanical properties of the sclera, and reveals a new area for our future work.
Terai, Naim; Schlötzer-Schrehardt, Ursula; Spoerl, Eberhard; Hornykewycz, Karin; Haentzschel, Janek; Haustein, Michael; Pillunat, Lutz E
2012-01-01
To investigate a possible association between the biomechanical load and unload behaviour and the elastin content of the sclera canal ring (SCR) and a superiorly localized sclera ring (SPS) in the porcine eye. Two sclera rings were trephined from each of 40 porcine eyes, one containing the SCR and the other an SPS. The load and the unload curves were measured in the extension range of 0-2.0 mm by a biomaterial tester. Hysteresis was determined from the area enclosed by the loading and unloading curve. Histochemical staining with resorcin-fuchsin and morphometric analysis of paraffin-embedded sections of both rings were performed to detect the area occupied by elastin fibres. At 1 mm extension, the mean load of the SCR was 0.89 ± 0.22 N and that of the SPS 1.13 ± 0.19 N, which was not significantly different between both rings (p > 0.05). Mean hysteresis in the SCR was 1.55 ± 0.30 N × mm and 1.90 ± 0.18 N × mm in the SPS, which was significantly different between both rings (p = 0.01). Mean sclera thickness was 986 μm in the SCR (range: 900-1,060 μm) and 971 μm in the SPS (range: 800-1,200 μm) without a statistically significant difference between both sclera rings (p = 0.78). The area occupied by elastin fibres was 15.5 ± 3.4% in the SCR and 4.5 ± 1.5% in the SPS, which was significantly different between both rings (p = 0.0001). Hysteresis in the SCR was significantly lower than in the SPS, indicating a higher elasticity of the SCR in the porcine eye. This effect could be explained by a higher content of elastin in the surrounding ring of the peripapillary optic nerve head providing reversible contraction in cases of intra-ocular pressure variations. Copyright © 2011 S. Karger AG, Basel.
Thakur, Ashish; Kadam, Rajendra S.
2011-01-01
The influence of drug properties including solubility, lipophilicity, tissue partition coefficients, and in vitro transscleral permeability on ex vivo and in vivo transscleral delivery from corticosteroid suspensions was determined. Solubility, tissue/buffer partition coefficients for bovine sclera and choroid-retinal pigment epithelium (CRPE), and in vitro bovine sclera and sclera-choroid-retinal pigment epithelium (SCRPE) transscleral transport were determined at pH 7.4 for triamcinolone, prednisolone, dexamethasone, fluocinolone acetonide, triamcinolone acetonide, and budesonide in solution. Ex vivo and in vivo transscleral delivery was assessed in Brown Norway rats after posterior subconjunctival injection of a 1 mg/ml suspension of each corticosteroid. Corticosteroid solubility and partition coefficients ranged from ∼17 to 300 μg/ml and 3.0 to 11.4 for sclera and from 7.1 to 35.8 for CRPE, respectively, with the more lipophilic molecules partitioning more into both tissues. Transport across sclera and SCRPE was in the range of 3.9 to 10.7% and 0.3 to 1.8%, respectively, with the transport declining with an increase in lipophilicity. Ex vivo and in vivo transscleral delivery indicated tissue distribution in the order CRPE ≥ sclera > retina > vitreous. Tissue partitioning showed a positive correlation with drug lipophilicity (R2 = 0.66–0.96). Ex vivo and in vivo sclera, CRPE, retina, and vitreous tissue levels of all corticosteroids showed strong positive correlation with drug solubility (R2 = 0.91–1.0) but not lipophilicity (R2 = 0.24–0.41) or tissue partitioning (R2 = 0.24–0.46) when delivered as suspensions. In vivo delivery was lower in all eye tissues assessed than ex vivo delivery, with the in vivo/ex vivo ratios being the lowest in the vitreous (0.085–0.212). Upon exposure to corticosteroid suspensions ex vivo or in vivo, transscleral intraocular tissue distribution was primarily driven by the drug solubility. PMID:21346004
Transscleral thermotherapy with laser-induced and conductive heating in hamster Greene melanoma.
Rem, Alex I; Oosterhuis, Jendo A; Keunen, Jan E E; Journée-De Korver, Hanneke G
2004-10-01
The purpose of this study was to investigate the cytotoxic effect of heat as induced by transscleral thermotherapy (TSTT), which may be of interest in the treatment of patients with choroidal melanoma. The aim of TSTT is to heat both the sclera and the tumor up to a cytotoxic temperature of about 60 degrees C. TSTT was performed in hamsters with subcutaneously implanted Greene melanoma covered by a specimen of human donor sclera of thickness 0.5, 0.7 or 0.9 mm. A newly developed applicator, which combines conductive episcleral heating at 60 degrees C with laser-induced heating, was used at laser powers ranging from 500 to 1500 mW delivered by an 810 nm diode laser, beam diameter 3 mm, and exposure time 1 min. Temperatures were measured at the scleral surface and at the sclera-tumor interface. The extent of tumor necrosis was examined by light microscopy and the sclera was examined by polarized light microscopy. Maximal depth of tumor necrosis without scleral damage was 4.4 (SD 1.5) mm. The temperature at the scleral surface after TSTT was 58.8 (SD 2.4) degrees C. The temperature at the sclera-tumor interface ranged from 56.4 (SD 3.7) degrees C at 500 mW to 65.3 (SD 4.4) degrees C at 1250 mW laser power. Structural changes to the scleral collagen started to develop at 1250 mW. TSTT with combined laser-induced and conductive heating caused cytotoxic temperatures in the tumor and the sclera, which were well tolerated by the scleral collagen.
NASA Astrophysics Data System (ADS)
Sun, Hui; Fan, Zhongwei; Yan, Ying; Lian, Fuqiang; Kurtz, Ron; Juhasz, Tibor
2016-03-01
Glaucoma is the second-leading cause of blindness worldwide and is often associated with elevated intraocular pressure (IOP). Partial-thickness drainage channels can be created with femtosecond laser in the translucent sclera for the potential treatment of glaucoma. We demonstrate the creation of partial-thickness subsurface drainage channels with the femtosecond laser in the cadaver human eyeballs and describe the application of two-photon microscopy and confocal microscopy for noninvasive imaging of the femtosecond laser created partial-thickness scleral channels in cadaver human eyes. A femtosecond laser operating at a wavelength of 1700 nm was scanned along a rectangular raster pattern to create the partial thickness subsurface drainage channels in the sclera of cadaver human eyes. Analysis of the dimensions and location of these channels is important in understanding their effects. We describe the application of two-photon microscopy and confocal microscopy for noninvasive imaging of the femtosecond laser created partial-thickness scleral channels in cadaver human eyes. High-resolution images, hundreds of microns deep in the sclera, were obtained to allow determination of the shape and dimension of such partial thickness subsurface scleral channels. Our studies suggest that the confocal and two-photon microscopy can be used to investigate femtosecond-laser created partial-thickness drainage channels in the sclera of cadaver human eyes.
NASA Astrophysics Data System (ADS)
Iomdina, Elena N.; Goltsman, Gregory N.; Seliverstov, Sergey V.; Sianosyan, Alisa A.; Teplyakova, Kseniya O.; Rusova, Anastasia A.
2016-09-01
An adequate water balance (hydration extent) is one of the basic factors of normal eye function, including its external shells: the cornea and the sclera. Adequate control of corneal and scleral hydration is very important for early diagnosis of a variety of eye diseases, stating indications for and contraindications against keratorefractive surgeries and the choice of contact lens correction solutions. THz systems of creating images in reflected beams are likely to become ideal instruments of noninvasive control of corneal and scleral hydration degrees. This paper reports on the results of a study involving transmittance and reflectance spectra for the cornea and the sclera of rabbit and human eyes, as well as those of the rabbit eye, in the frequency range of 0.13 to 0.32 THz. The dependence of the reflectance coefficient of these tissues on water mass percentage content was determined. The experiments were performed on three corneas, three rabbit scleras, two rabbit eyes, and three human scleras. The preliminary results demonstrate that the proposed technique, based on the use of a continuous THz radiation, may be utilized to create a device for noninvasive control of corneal and scleral hydration, which has clear potential of broad practical application.
Coudrillier, Baptiste; Pijanka, Jacek K.; Jefferys, Joan L.; Goel, Adhiraj; Quigley, Harry A.; Boote, Craig; Nguyen, Thao D.
2015-01-01
Objective The biomechanical behavior of the sclera determines the level of mechanical insult from intraocular pressure to the axons and tissues of the optic nerve head, as is of interest in glaucoma. In this study, we measure the collagen fiber structure and the strain response, and estimate the material properties of glaucomatous and normal human donor scleras. Methods Twenty-two posterior scleras from normal and diagnosed glaucoma donors were obtained from an eyebank. Optic nerve cross-sections were graded to determine the presence of axon loss. The specimens were subjected to pressure-controlled inflation testing. Full-field displacement maps were measured by digital image correlation (DIC) and spatially differentiated to compute surface strains. Maps of the collagen fiber structure across the posterior sclera of each inflated specimen were obtained using synchrotron wide-angle X-ray scattering (WAXS). Finite element (FE) models of the posterior scleras, incorporating a specimen-specific representation of the collagen structure, were constructed from the DIC-measured geometry. An inverse finite element analysis was developed to estimate the stiffness of the collagen fiber and inter-fiber matrix. Results The differences between glaucoma and non-glaucoma eyes were small in magnitude. Sectorial variations of degree of fiber alignment and peripapillary scleral strain significantly differed between normal and diagnosed glaucoma specimens. Meridional strains were on average larger in diagnosed glaucoma eyes compared with normal specimens. Non-glaucoma specimens had on average the lowest matrix and fiber stiffness, followed by undamaged glaucoma eyes, and damaged glaucoma eyes but the differences in stiffness were not significant. Conclusion The observed biomechanical and microstructural changes could be the result of tissue remodeling occuring in glaucoma and are likely to alter the mechanical environment of the optic nerve head and contribute to axonal damage. PMID:26161963
Enhancement of scleral macromolecular permeability with prostaglandins.
Weinreb, R N
2001-01-01
PURPOSE: It is proposed that the sclera is a metabolically active and pharmacologically responsive tissue. These studies were undertaken to determine whether prostaglandin exposure can enhance scleral permeability to high-molecular-weight substances. METHODS: Topical prostaglandin F2 alpha (PGF2 alpha) was administered to monkeys to determine if this altered the amount of scleral matrix metalloproteinases (MMPs). Experiments also were performed to determine whether the prostaglandin F (FP) receptor and gene transcripts are expressed in normal human sclera. Permeability of organ-cultured human sclera following prostaglandin exposure then was studied and the amount of MMP released into the medium measured. Finally, the permeability of human sclera to basic fibroblast growth factor (FGF-2) was determined following prostaglandin exposure. RESULTS: Topical prostaglandin administration that reduced scleral collagen also increased scleral MMP-1, MMP-2, and MMP-3 by 63 +/- 35%, 267 +/- 210%, and 729 +/- 500%, respectively. FP receptor protein was localized in scleral fibroblasts, and FP receptor gene transcript was identified in sclera. Exposure to prostaglandin F2 alpha, 17-phenyltrinor, PGF2 alpha, or latanoprost acid increased scleral permeability by up to 124%, 183%, or 213%, respectively. In these cultures, MMP-1, MMP-2, and MMP-3 were increased by up to 37%, 267%, and 96%, respectively. Finally, transscleral absorption of FGF-2 was increased by up to 126% with scleral exposure to latanoprost. CONCLUSIONS: These studies demonstrate that the sclera is metabolically active and pharmacologically responsive to prostaglandins. Further, they demonstrate the feasibility of cotreatment with prostaglandin to enhance transscleral delivery of peptides, such as growth factors and high-molecular-weight substances, to the posterior segment of the eye. PMID:11797317
Dakubo, Gabriel D; Mazerolle, Chantal; Furimsky, Marosh; Yu, Chuan; St-Jacques, Benoit; McMahon, Andrew P; Wallace, Valerie A
2008-08-01
The development of extraocular orbital structures, in particular the choroid and sclera, is regulated by a complex series of interactions between neuroectoderm, neural crest and mesoderm derivatives, although in many instances the signals that mediate these interactions are not known. In this study we have investigated the function of Indian hedgehog (Ihh) in the developing mammalian eye. We show that Ihh is expressed in a population of non-pigmented cells located in the developing choroid adjacent to the RPE. The analysis of Hh mutant mice demonstrates that the RPE and developing scleral mesenchyme are direct targets of Ihh signaling and that Ihh is required for the normal pigmentation pattern of the RPE and the condensation of mesenchymal cells to form the sclera. Our findings also indicate that Ihh signals indirectly to promote proliferation and photoreceptor specification in the neural retina. This study identifies Ihh as a novel choroid-derived signal that regulates RPE, sclera and neural retina development.
Murienne, Barbara J.; Jefferys, Joan L.; Quigley, Harry A.; Nguyen, Thao D.
2014-01-01
Pathological changes in scleral glycosaminoglycan (GAG) content and in scleral mechanical properties have been observed in eyes with glaucoma and myopia. The purpose of this study is to investigate the effect of GAG removal on the scleral mechanical properties to better understand the impact of GAG content variations in the pathophysiology of glaucoma and myopia. We measured how the removal of sulphated GAG (s-GAG) affected the hydration, thickness and mechanical properties of the posterior sclera in enucleated eyes of 6–9 month-old pigs. Measurements were made in 4 regions centered on the optic nerve head (ONH) and evaluated under 3 conditions: no treatment (control), after treatment in buffer solution alone, and after treatment in buffer containing chondroitinase ABC (ChABC) to remove s-GAGs. The specimens were mechanically tested by pressure-controlled inflation with full-field deformation mapping using digital image correlation (DIC). The mechanical outcomes described the tissue tensile and viscoelastic behavior. Treatment with buffer alone increased the hydration of the posterior sclera compared to controls, while s-GAG removal caused a further increase in hydration compared to buffer-treated scleras. Buffer-treatment significantly changed the scleral mechanical behavior compared to the control condition, in a manner consistent with an increase in hydration. Specifically, buffer-treatment led to an increase in low-pressure stiffness, hysteresis, and creep rate, and a decrease in high-pressure stiffness. ChABC-treatment on buffer-treated scleras had opposite mechanical effects than buffer-treatment on controls, leading to a decrease in low-pressure stiffness, hysteresis, and creep rate, and an increase in high-pressure stiffness and transition strain. Furthermore, s-GAG digestion dramatically reduced the differences in the mechanical behavior among the 4 quadrants surrounding the ONH as well as the differences between the circumferential and meridional responses compared to the buffer-treated condition. These findings demonstrate a significant effect of s-GAGs on both the stiffness and time-dependent behavior of the sclera. Alterations in s-GAG content may contribute to the altered creep and stiffness of the sclera of myopic and glaucoma eyes. PMID:25448352
NASA Astrophysics Data System (ADS)
Ghosn, Mohamad G.; Tuchin, Valery V.; Larin, Kirill V.
2009-02-01
Aside from other ocular drug delivery methods, topical application and follow up drug diffusion through the cornea and sclera of the eye remain the favored method, as they impose the least pain and discomfort to the patient. However, this delivery route suffers from the low permeability of epithelial tissues and drug washout, thus reducing the effectiveness of the drug and ability to reach its target in effective concentrations. In order to better understand the behavioral characteristics of diffusion in ocular tissue, a method for noninvasive imaging of drug diffusion is needed. Due to its high resolution and depth-resolved imaging capabilities, optical coherence tomography (OCT) has been utilized in quantifying the molecular transport of different drugs and analytes in vitro in the sclera and the cornea. Diffusion of Metronidazole (0.5%), Dexamethasone (0.2%), Ciprofloxacin (0.3%), Mannitol (20%), and glucose solution (20%) in rabbit sclera and cornea were examined. Their permeability coefficients were calculated by using OCT signal slope and depth-resolved amplitude methods as function of time and tissue depth. For instance, mannitol was found to have a permeability coefficient of (8.99 +/- 1.43) × 10-6 cm/s in cornea (n=4) and (6.18 +/- 1.08) × 10-6 cm/s in sclera (n=5). We also demonstrate the capability of OCT technique for depth-resolved monitoring and quantifying of glucose diffusion in different layers of the sclera. We found that the glucose diffusion rate is not uniform throughout the tissue and is increased from approximately (2.39 +/- 0.73) × 10-6 cm/s at the epithelial side to (8.63 +/- 0.27) × 10-6 cm/s close to the endothelial side of the sclera. In addition, discrepancy in the permeability rates of glucose solutions with different concentrations was observed. Such diffusion studies could enhance our knowledge and potentially pave the way for advancements of therapeutic and diagnostic techniques in the treatment of ocular diseases.
Transscleral diffusion of ethacrynic acid and sodium fluorescein
Lin, Cheng-Wen; Wang, Yong; Challa, Pratap; Epstein, David L.
2007-01-01
Purpose One of the current limitations in developing novel glaucoma drugs that target the trabecular meshwork (TM) is the induced corneal toxicity from eyedrop formulations. To avoid the corneal toxicity, an alternative approach would be to deliver TM drugs through the sclera. To this end, we quantified ex vivo diffusion coefficient of a potential TM drug, ethacrynic acid (ECA), and investigated mechanisms of ECA transport in the sclera. Methods An Ussing-type diffusion apparatus was built to measure the apparent diffusion coefficient of ECA in fresh porcine sclera at 4 °C. To understand mechanisms of ECA transport, we quantified the transscleral transport of a fluorescent tracer, sodium fluorescein (NaF), that has a similar molecular weight but is more hydrophilic compared to ECA. Furthermore, we developed a mathematical model to simulate the transport processes and used it to analyze the experimental data. The model was also used to investigate the dependence of diffusion coefficients on volume fraction of viable cells and the binding of NaF and ECA to scleral tissues. Results The diffusion coefficients of ECA and NaF in the sclera were 48.5±15.1x10-7 cm2/s (n=9) and 5.23±1.93x10-7 cm2/s (n=8), respectively. Both diffusion coefficients were insensitive to cell shrinkage caused by ECA during the diffusion experiments and cell damage caused by the storage of tissues ex vivo before the experiments. Binding of ECA to scleral tissues could not be detected. The apparent maximum binding capacity and the apparent equilibrium dissociation constant for NaF were 80±5 mM and 2.5±0.5 mM (n=3), respectively. Conclusions These data demonstrated that ECA diffusion was minimally hindered by structures in the sclera, presumably due to the lack of cells and binding sites for ECA in the sclera. PMID:17356511
MMP-2 participates in the sclera of guinea pig with form-deprivation myopia via IGF-1/STAT3 pathway.
Liu, Y-X; Sun, Y
2018-05-01
To investigate the expression changes of MMP-2 (matrix metalloproteinases-2) mediated by IGF-1 (insulin-like growth factors-1) STAT3 (signal transducer and activator of transcription 3) pathway in the sclera of the form-deprivation myopia guinea pigs. Twenty-four three-week-old guinea pigs were randomly divided into 4 groups: group A (Control), B, C and D. Guinea pigs in group A were sacrificed after 21 days without any special treatment. Guinea pigs in group B were sacrificed 7 days after receiving stitch in the right eye. Guinea pigs in group C were sacrificed 14 days after receiving stitch in the right eye. Guinea pigs in group D were sacrificed 21 days after receiving stitch in the right eye. Eyeball refraction and axial length of guinea pigs were measured before sacrifice. Eyeballs of guinea pigs were enucleated after sacrifice. The expressions of IGF-1, STAT3 and MMP-2 in scleral tissue were detected by Western blot. Axial length extension and myopia appeared in the right eye of guinea pigs in group B. The expressions of IGF-1, STAT3 and MMP-2 in the sclera significantly increased after 7 days of occlusion compared with that in control group A (p<0.05). In the right eye of group C, the axial prolongation and myopia formation appeared after 14-day occlusion. The expressions of IGF-1, STAT3 and MMP-2 in sclera significantly increased compared with that in group A (p<0.05). In the right eye of group D, the axial extension and myopia formation occurred. IGF-1, STAT3 and MMP-2 in scleral significantly upregulated 21 days after occlusion (p<0.05). Furthermore, at different stages of deprivation, protein expressions of MMP-2 and IGF-1 in sclera were positively correlated (r = 0.962, p<0.01). Form-deprivation of guinea pigs lead to increased expressions of IGF-1, STAT3 and MMP-2 in the sclera and myopia of guinea pigs. The expressions of IGF-1, STAT3 and MMP-2 increased progressively over the time of deprivation. Additionally, overexpression of MMP-2 mediated by IGF-1/STAT3 pathway in sclera might promote the formation of myopia.
Cheruvu, Narayan P. S.; Kompella, Uday B.
2012-01-01
Purpose To determine the influence of the choroid–Bruch’s layer and solute lipophilicity on in vitro transscleral drug permeability in bovine and porcine eyes. Methods The in vitro permeability of two VEGF inhibitory drugs, budesonide and celecoxib, which are lipophilic and neutral at physiologic pH, and of three marker solutes, 3H-mannitol (hydrophilic, neutral), sodium fluorescein (hydrophilic, anionic), and rhodamine 6G (lipophilic, cationic), were determined across freshly excised scleras, with or without the underlying choroid–Bruch’s layer. Select studies were performed using porcine sclera with and without choroid–Bruch’s layer. Neural retina was removed by exposure of the eyecup to isotonic buffer and wherever required, the retinal pigment epithelial (RPE) layer of the preparation was disrupted and removed by exposure to hypertonic buffer. Because of the poor solubility of celecoxib and budesonide, permeability studies were conducted with 5% wt/vol of hydroxypropyl-β-cyclodextrin (HPβCD). For other solutes, permeability studies were conducted, with and without HPβCD. Partitioning of the solutes into bovine sclera and choroid–Bruch’s layer was also determined. Results The calculated log (distribution coefficient) values were −2.89, −0.68, 2.18, 3.12, and 4.02 for mannitol, sodium fluorescein, budesonide, celecoxib, and rhodamine 6G, respectively. Removal of RPE was confirmed by transmission electron microscopy and differences in the transport of mannitol. The order of the permeability coefficients (Papp) across sclera and sclera–choroid–Bruch’s layers in bovine and porcine models was 3H-mannitol > fluorescein > budesonide > celecoxib > rhodamine 6G, with HPβCD, and 3H-mannitol > fluorescein > rhodamine 6G, without HPβCD. The presence of choroid–Bruch’s layer reduced the bovine scleral permeability by 2-, 8-, 16-, 36-, and 50-fold and porcine tissue permeability by 2-, 7-, 15-, 33-, and 40-fold, respectively, for mannitol, sodium fluorescein, budesonide, celecoxib, and rhodamine 6G. The partition coefficients measured in bovine tissues correlated positively with the log (distribution coefficient) and exhibited a trend opposite that of transport. The partition coefficient ratio of bovine choroid–Bruch’s layer to sclera was ~1, 1.5, 1.7, 2, and 3.5, respectively, for the solutes, as listed earlier. Conclusions The choroid–Bruch’s layer is a more significant barrier to drug transport than is sclera. It hinders the transport of lipophilic solutes, especially a cationic solute, more than hydrophilic solutes and in a more dramatic way than does sclera. The reduction in transport across this layer directly correlates with solute binding to the tissue. Understanding the permeability properties of sclera and underlying layers would be beneficial in designing better drugs for transscleral delivery. PMID:17003447
Sutureless human sclera donor patch graft for Ahmed glaucoma valve.
Zeppa, Lucio; Romano, Mario R; Capasso, Luigi; Tortori, Achille; Majorana, Mara A; Costagliola, Ciro
2010-01-01
To report the safety and effectiveness of a sutureless human sclera donor patch graft covering the subconjunctival portion of glaucoma drainage implant tube to prevent its erosion throughout the overlying conjunctiva. This was a prospective pilot study. Fifteen eyes of 15 consecutive patients not responsive to medical and to not-implant surgical glaucoma treatment underwent Ahmed glaucoma valve (AGV) implant surgery with sutureless human sclera donor patch graft. The surgical procedure included AVG implant placed 8 mm behind the corneal limbus and fixed to the sclera with two 9-0 black nylon sutures. The tube was passed through the scleral tunnel, parallel to the corneal limbus, and shortened at the desired length. The anterior part of the tube was covered with human donor scleral graft and kept in place with fibrin glue (Tissue Coll) under the conjunctiva. Examinations were scheduled at baseline and then at 1 week and 1, 3, 6, and 12 months after surgery. At 12-month follow-up, the best-corrected visual acuity did not significantly improve from baseline 0.78+/-1.2 logMAR, whereas mean intraocular pressure significantly decreased from preoperative values of 29.8 (SD 8.4) mmHg. In all cases, the scleral patch was found in place at each check during the follow-up period. No conjunctival erosion over the AGV tube nor sign of endophthalmitis was recorded at any time during the follow-up period. AVG implant surgery with sutureless human sclera donor patch graft represents an effective and relatively safe surgical procedure for complicated glaucomas, avoiding conjunctival erosions over the AGV tube.
Fazio, Massimo A.; Grytz, Rafael; Morris, Jeffrey S.; Bruno, Luigi; Girkin, Christopher A.; Downs, J. Crawford
2014-01-01
Purpose. We tested the hypothesis that the variation of peripapillary scleral structural stiffness with age is different in donors of European (ED) and African (AD) descent. Methods. Posterior scleral shells from normal eyes from donors of European (n = 20 pairs; previously reported) and African (n = 9 pairs) descent aged 0 and 90 years old were inflation tested within 48 hours post mortem. Scleral shells were pressurized from 5 to 45 mm Hg and the full-field, 3-dimensional (3D) deformation of the outer surface was recorded at submicrometric accuracy using speckle interferometry (ESPI). Mean maximum principal (tensile) strain of the peripapillary and midperipheral regions surrounding the optic nerve head (ONH) were fit using a functional mixed effects model that accounts for intradonor variability, same-race correlation, and spatial autocorrelation to estimate the effect of race on the age-related changes in mechanical scleral strain. Results. Mechanical tensile strain significantly decreased with age in the peripapillary sclera in the African and European descent groups (P < 0.001), but the age-related stiffening was significantly greater in the African descent group (P < 0.05). Maximum principal strain in the peripapillary sclera was significantly higher than in the midperipheral sclera for both ethnic groups. Conclusions. The sclera surrounding the ONH stiffens more rapidly with age in the African descent group compared to the European group. Stiffening of the peripapillary sclera with age may be related to the higher prevalence of glaucoma in the elderly and persons of African descent. PMID:25237162
Fazio, Massimo A; Grytz, Rafael; Morris, Jeffrey S; Bruno, Luigi; Girkin, Christopher A; Downs, J Crawford
2014-09-18
We tested the hypothesis that the variation of peripapillary scleral structural stiffness with age is different in donors of European (ED) and African (AD) descent. Posterior scleral shells from normal eyes from donors of European (n = 20 pairs; previously reported) and African (n = 9 pairs) descent aged 0 and 90 years old were inflation tested within 48 hours post mortem. Scleral shells were pressurized from 5 to 45 mm Hg and the full-field, 3-dimensional (3D) deformation of the outer surface was recorded at submicrometric accuracy using speckle interferometry (ESPI). Mean maximum principal (tensile) strain of the peripapillary and midperipheral regions surrounding the optic nerve head (ONH) were fit using a functional mixed effects model that accounts for intradonor variability, same-race correlation, and spatial autocorrelation to estimate the effect of race on the age-related changes in mechanical scleral strain. Mechanical tensile strain significantly decreased with age in the peripapillary sclera in the African and European descent groups (P < 0.001), but the age-related stiffening was significantly greater in the African descent group (P < 0.05). Maximum principal strain in the peripapillary sclera was significantly higher than in the midperipheral sclera for both ethnic groups. The sclera surrounding the ONH stiffens more rapidly with age in the African descent group compared to the European group. Stiffening of the peripapillary sclera with age may be related to the higher prevalence of glaucoma in the elderly and persons of African descent. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
Ultrastructure of the extracellular matrix of bovine dura mater, optic nerve sheath and sclera.
Raspanti, M; Marchini, M; Della Pasqua, V; Strocchi, R; Ruggeri, A
1992-10-01
The sclera, the outermost sheath of the optic nerve and the dura mater have been investigated histologically and ultrastructurally. Although these tissues appear very similar under the light microscope, being dense connective tissues mainly composed of collagen bundles and a limited amount of cells and elastic fibres, they exhibit subtle differences on electron microscopy. In the dura and sclera collagen appears in the form of large, nonuniform fibrils, similar to those commonly found in tendons, while in the optic nerve sheath the fibrils appear smaller and uniform, similar to those commonly observed in reticular tissues, vessel walls and skin. Freeze-fracture also reveals these fibrils to have different subfibrillar architectures, straight or helical, which correspond to 2 distinct forms of collagen fibril previously described (Raspanti et al. 1989). The other extracellular matrix components also vary with the particular collagen fibril structure. Despite their common embryological derivation, the dura mater, optic nerve sheath and sclera exhibit diversification of their extracellular matrix consistent with the mechanical loads to which these tissues are subjected. Our observations indicate that the outermost sheath of the optic nerve resembles the epineurium of peripheral nerves rather than the dura to which it is commonly likened.
Identification of Multipotent Stem/Progenitor Cells in Murine Sclera
Tsai, Chia-Ling; Wu, Pei-Chang; Fini, M. Elizabeth; Shi, Songtao
2011-01-01
Purpose. The sclera forms the fibrous outer coat of the eyeball and acts as a supportive framework. The purpose of this study was to examine whether the sclera contains mesenchymal stem/progenitor cells. Method. Scleral tissue from C57BL6/J mice was separated from the retina and choroid and subsequently enzyme digested to release single cells. Proliferation capacity, self-renewal capacity, and ability for multipotent differentiation were analyzed by BrdU labeling, flow cytometry, reverse transcriptase–polymerase chain reaction, immunocytochemistry, and in vivo transplantation. Results. The scleral stem/progenitor cells (SSPCs) possessed clonogenic and high doubling capacities. These cells were positive for the mesenchymal markers Sca-1, CD90.2, CD44, CD105, and CD73 and negative for the hematopoietic markers CD45, CD11b, Flk1, CD34, and CD117. In addition to expressing stem cell genes ABCG2, Six2, Notch1, and Pax6, SSPCs were able to differentiate to adipogenic, chondrogenic, and neurogenic lineages. Conclusions. This study indicates that the sclera contains multipotent mesenchymal stem cells. Further study of SSPCs may help elucidate the cellular and molecular mechanism of scleral diseases such as scleritis and myopia. PMID:21788434
Quigley, Harry A.; Cone, Frances E.
2013-01-01
There is considerable evidence that the state of ocular connective tissues and their response in glaucomatous disease affects the degree of glaucoma damage. Both experimental and clinical data suggest that improved diagnostic and prognostic information could be derived from assessment of the mechanical responsiveness of the sclera and lamina cribrosa to intraocular pressure (IOP). Controlled mutagenesis of the sclera has produced a mouse strain that is relatively resistant to increased IOP. Alteration of the baseline scleral state could be accomplished through either increased cross-linking of fibrillar components or their reduction. The sclera is a dynamic structure, altering its structure and behavior in response to IOP change. The biochemical pathways that control these responses are fertile areas for new glaucoma treatments. PMID:23535950
WE-A-17A-12: The Influence of Eye Plaque Design On Dose Distributions and Dose- Volume Histograms
DOE Office of Scientific and Technical Information (OSTI.GOV)
Aryal, P; Molloy, JA; Rivard, MJ
Purpose: To investigate the effect of slot design of the model EP917 plaque on dose distributions and dose-volume histograms (DVHs). Methods: The dimensions and orientation of the slots in EP917 plaques were measured. In the MCNP5 radiation simulation geometry, dose distributions on orthogonal planes and DVHs for a tumor and sclera were generated for comparisons. 27 slot designs and 13 plaques were evaluated and compared with the published literature and the Plaque Simulator clinical treatment planning system. Results: The dosimetric effect of the gold backing composition and mass density was < 3%. Slot depth, width, and length changed the centralmore » axis (CAX) dose distributions by < 1% per 0.1 mm in design variation. Seed shifts in the slot towards the eye and shifts of the {sup 125} I-coated Ag rod within the capsule had the greatest impact on CAX dose distribution, increasing by 14%, 9%, 4%, and 2.5% at 1, 2, 5, and 10 mm, respectively, from the inner sclera. Along the CAX, dose from the full plaque geometry using the measured slot design was 3.4% ± 2.3% higher than the manufacturer-provided geometry. D{sub 10} for the simulated tumor, inner sclera, and outer sclera for the measured plaque was also higher, but 9%, 10%, and 20%, respectively. In comparison to the measured plaque design, a theoretical plaque having narrow and deep slots delivered 30%, 37%, and 62% lower D{sub 10} doses to the tumor, inner sclera, and outer sclera, respectively. CAX doses at −1, 0, 1, and 2 mm were also lower by a factor of 2.6, 1.4, 1.23, and 1.13, respectively. Conclusion: The study identified substantial sensitivity of the EP917 plaque dose distributions to slot design. However, it did not identify substantial dosimetric variations based on radionuclide choice ({sup 125}I, {sup 103}Pd, or {sup 131}Cs). COMS plaques provided lower scleral doses with similar tumor dose coverage.« less
NASA Astrophysics Data System (ADS)
Schultz, David Sheldon
Countless debilitating pathologies exhibit symptoms that result from altered mechanical behavior of soft tissue. Therefore, it is of clinical and economic importance to mechanically evaluate soft tissues and attribute degenerative changes to alterations in structural constituents. The studies presented here focus on the annulus fibrosus and the sclera. Failure in these tissues is common and catastrophic. The annulus fibrosus may fail, resulting in herniation and nerve impingement, or the disc may degenerate over time, resulting in reduced mobility and pain. Similarly, the sclera may degenerate over time with intraocular pressure spurring creep behavior that distends the eye beyond its ideal shape. This causes myopic vision and puts patients at risk of macular degeneration and retinal detachment. These two tissues share a common structural role as the outer wall of a pressure vessel. Also, they are made of strikingly similar constituents, primarily consisting of water, type I collagen, glycosaminoglycans and elastin. The microstructure of these tissues, however, is very different. The annulus fibrosus is representative of an anisotropic tissue. Its well-organized fibril structure was analyzed via polarization modulated second harmonic microscopy in order to characterize fibril architecture. Structurally relevant biochemical constituents were quantified with biochemical assays. Morphologically healthy annulus tended to have a more highly organized microstructure and tended to absorb more strain energy when subject to a tensile load cycle. Given the strong correlation between fibril organization and select mechanical properties, predictive models will likely benefit from a characterization of fibril continuity and orientation coherence. The sclera is representative of an isotropic tissue. Its less-organized fibril structure has evolved to sustain biaxial plane stress. In the sclera, collagen content and associated crosslinks were primary determinants of stiffness. Substantial collagen crosslink accumulation is a primary factor causing the stiffening of sclera with increased age. The influence of crosslinks dominates diffusion and permeability behavior. Exogenous crosslinking may help modulate the mechanical and fluid transport properties of the sclera and cornea. Treatment with methylglyoxal reduces the permeability and increases the stiffness of both. However, differences in the pre-treatment level of organization within the microstructure encourages asymmetric results.
Sclera-Choroid-RPE Transport of Eight β-Blockers in Human, Bovine, Porcine, Rabbit, and Rat Models
Kadam, Rajendra S.; Cheruvu, Narayan P. S.; Edelhauser, Henry F.
2011-01-01
Purpose. To determine the influence of drug lipophilicity, ocular pigmentation, and species differences on transscleral solute transport. Methods. The transport of eight β-blockers across excised sclera/sclera-choroid-RPE (SCRPE) of albino rabbit, pigmented rabbit, human, porcine, and bovine eyes was determined over 6 hours. The ex vivo transscleral β-blocker transport to the vitreous at the end of 6 hours was determined in euthanatized, pigmented Brown Norway rats. The thicknesses of the sclera and SCRPE and the melanin content in choroid-RPE (CRPE) were measured to determine whether species differences in drug transport can be explained on this basis. Results. Solute lipophilicity inversely correlated with the SCRPE cumulative percentage of transport in all species (R2 ≥ 0.80). The CRPE impeded the SCRPE transport of all β-blockers (51%–64% resistance in the rabbits; 84%–99.8% in the bovine and porcine eyes) more than the sclera, with the impedance increasing with lipophilicity. SCRPE transport followed the trend albino rabbit > pigmented rabbit > human > porcine > bovine, and a cross-species comparison showed good Spearman's rho correlation (R2 ≥ 0.85). Bovine (R2 = 0.84), porcine (R2 = 0.84), and human (R2 = 0.71) SCRPE transport was more predictive than that in the rabbit models (R2 = 0.60–0.61) of transscleral solute transport to the vitreous in rats. The CRPE concentrations were higher in pigmented rabbits than in albino rabbits. The melanin content of the CRPE exhibited the trend albino rabbit ≪ pigmented rabbit < porcine ∼ bovine < rat. Normalization to scleral thickness abolished the species differences in scleral transport. Normalization to SCRPE thickness and melanin content significantly reduced species differences in SCRPE transport. Conclusions. Owing to the presence of pigment and drug binding, choroid-RPE is the principal barrier to transscleral β-blocker transport, with the barrier being more significant for lipophilic β-blockers. Although different in magnitude between species, sclera/SCRPE transport can be correlated between species. Tissue thickness accounts for the species differences in scleral transport. Differences in tissue thickness and melanin content largely account for the species differences in SCRPE transport. PMID:21282583
Morris, Hugh J.; Tang, Junhua; Cruz Perez, Benjamin; Pan, Xueliang; Hart, Richard T.; Weber, Paul A.; Liu, Jun
2013-01-01
Purpose. This study tested the hypothesis that intraocular pressure (IOP) elevations, induced by controlled increase of intraocular volume, are correlated with the biomechanical responses of the posterior sclera. Methods. Porcine globes were tested within 48 hours postmortem. The first group of globes (n = 11) was infused with 15 μL of phosphate-buffered saline at three different rates to investigate rate-dependent IOP elevations. The second group (n = 16) was first infused at the fast rate and then underwent inflation tests to investigate the relationship between IOP elevations (ΔIOP) and scleral strains. The strains in the superotemporal region of the posterior sclera were measured by ultrasound speckle tracking. Linear regression was used to examine the association between ΔIOP due to micro-volumetric infusion and the scleral strains at a specific inflation pressure. Results. The average ΔIOP was 14.9 ± 4.3 mm Hg for the infusion of 15 μL in 1 second. The ΔIOP was greater for the faster infusion rates but highly correlated across different rates (P < 0.001). A significant negative association was found between the ΔIOP and the tangential strains in both the circumferential (R2 = 0.54, P = 0.003) and meridian (R2 = 0.53, P = 0.002) directions in the posterior sclera. Conclusions. This study showed a substantial increase in IOP, with a large intersubject variance during micro-volumetric change. A stiffer response of the sclera was associated with larger IOP spikes, providing experimental evidence linking corneoscleral biomechanics to IOP fluctuation. In vivo measurement of corneoscleral biomechanics may help better predict the dynamic profile of IOP. PMID:24130185
Majumdar, Soumyajit; Srirangam, Ramesh
2008-01-01
Purpose Hesperidin holds potential in treating age-related macular degeneration, cataract and diabetic retinopathy. The aim of this study, constituting the first step towards efficient ocular delivery of hesperidin, was to determine its physicochemical properties and in vitro ocular tissue permeability. Methods pH dependent aqueous solubility and stability were investigated following standard protocols. Permeability of hesperidin across excised rabbit cornea, sclera, and sclera plus retinal pigmented epithelium (RPE) was determined using a side-bi-side diffusion apparatus. Results Hesperidin demonstrated poor, pH independent, aqueous solubility. Solubility improved dramatically in the presence of 2-hydroxypropyl-beta-cyclodextrin (HP-β-CD) and the results supported 1:1 complex formation. Solutions were stable in the pH and temperature (25, 40°C) conditions tested, except for samples stored at pH 9. Transcorneal permeability in the apical-basal and basal-apical directions was 1.11±0.86×10−6 and 1.16±0.05×10−6 cm/s, respectively. The scleral tissue was more permeable (10.2±2.1×10−6cm/s). However, permeability across sclera/choroid/RPE in the sclera to retina and retina to sclera direction was 0.82±0.69×10−6, 1.52±0.78×10−6 cm/s, respectively, demonstrating the barrier properties of the RPE. Conclusion Our results suggest that stable ophthalmic solutions of hesperidin can be prepared and that hesperidin can efficiently permeate across the corneal tissue. Further investigation into its penetration into the back-of-the eye ocular tissues is warranted. PMID:18810327
Loch, Christian; Zakelj, Simon; Kristl, Albin; Nagel, Stefan; Guthoff, Rudolf; Weitschies, Werner; Seidlitz, Anne
2012-08-30
To treat ophthalmic diseases like glaucoma or inflammatory disorders topically applied ophthalmic formulations such as eye drops are usually used. In addition, novel ophthalmic implants releasing drug substances locally into different parts of the eye are available today. In the work presented here, the permeability coefficients of selected drugs (ciprofloxacin hydrochloride, lidocaine hydrochloride, timolol maleate) for ophthalmic tissues were determined using side-by-side diffusion chambers (so-called Ussing chambers). Sclera, conjunctiva, cornea, choroidea-retina-complex and a complex of conjunctiva-sclera-choroidea-retina were excised from fresh porcine, rabbit and bovine eyes. In the porcine eye tissues the highest P(app) values were obtained for conjunctiva with the exception of lidocaine. Therefore, it can be estimated that a certain amount of drug diffuses or is transported through conjunctiva after application. The P(app) values for sclera were also higher than those for cornea and even more, the surface area of sclera which is available for drug absorption is much larger than that of cornea when applying an implant. The obtained permeability coefficients for sclera and conjunctiva indicate that the administration of periocular implants can be an alternative to topically applied formulations. The complexes of the tissues were a significantly (p<0.01) stronger barrier to the investigated substances than the separated tissues. Distinct differences in permeability coefficients between the investigated animal tissues were observed. Overall the highest P(app) values for all mounted tissues were obtained with the rabbit, followed by porcine and bovine eyes. Because of these distinct interspecies differences one must be very careful when selecting the proper animal model for the permeability experiments. Copyright © 2012 Elsevier B.V. All rights reserved.
Kadam, Rajendra S.
2010-01-01
In vitro bovine eye tissue/phosphate-buffered saline, pH 7.4, partition coefficients (Kt:b), in vitro binding to natural melanin, and in vivo delivery at 1 h after posterior subconjunctival injection in Brown Norway rats were determined for eight β-blockers. The Kt:b was in the order intact tissue, dry weight method ≥ intact tissue, wet weight method corrected for tissue water and drug in tissue water ≫ intact tissue, wet weight method > homogenized tissue. In intact tissue methods, Kt:b followed the order choroid-retinal pigment epithelium (RPE) > trabecular meshwork > retina > sclera ∼ optic nerve; propranolol > betaxolol > pindolol ∼ timolol ∼ metoprolol > sotalol ∼ atenolol ∼ nadolol. Intact tissue, wet weight log (Kt:b) correlated positively with log D for all tissues (R2 of 0.7–0.9). Log (melanin binding capacity) correlated positively with choroid-RPE log (Kt:b) (R2 of 0.5). With an increase in concentration, Kt:b decreased in trabecular meshwork for all β-blockers and for some lipophilic β-blockers in choroid-RPE and sclera. With an increase in drug lipophilicity, in vivo tissue distribution increased in choroid-RPE, iris-ciliary body, sclera, and cornea but exhibited a declining trend in retina, vitreous, and lens. In vitro bovine intact tissue, wet weight Kt:b correlated positively with rat in vivo tissue/vitreous humor distribution for sclera, choroid-RPE, and retina (R2 of 0.985–0.993). In vitro tissue partition coefficients might be useful in predicting in vivo drug distribution after trans-scleral delivery. Less lipophilic solutes exhibiting limited nonproductive binding in choroid-RPE might exhibit greater trans-scleral delivery to the retina and vitreous. PMID:19926800
Age estimation based on aspartic acid racemization in human sclera.
Klumb, Karolin; Matzenauer, Christian; Reckert, Alexandra; Lehmann, Klaus; Ritz-Timme, Stefanie
2016-01-01
Age estimation based on racemization of aspartic acid residues (AAR) in permanent proteins has been established in forensic medicine for years. While dentine is the tissue of choice for this molecular method of age estimation, teeth are not always available which leads to the need to identify other suitable tissues. We examined the suitability of total tissue samples of human sclera for the estimation of age at death. Sixty-five samples of scleral tissue were analyzed. The samples were hydrolyzed and after derivatization, the extent of aspartic acid racemization was determined by gas chromatography. The degree of AAR increased with age. In samples from younger individuals, the correlation of age and D-aspartic acid content was closer than in samples from older individuals. The age-dependent racemization in total tissue samples proves that permanent or at least long-living proteins are present in scleral tissue. The correlation of AAR in human sclera and age at death is close enough to serve as basis for age estimation. However, the precision of age estimation by this method is lower than that of age estimation based on the analysis of dentine which is due to molecular inhomogeneities of total tissue samples of sclera. Nevertheless, the approach may serve as a valuable alternative or addition in exceptional cases.
Protective ocular mechanisms in woodpeckers.
Wygnanski-Jaffe, T; Murphy, C J; Smith, C; Kubai, M; Christopherson, P; Ethier, C R; Levin, A V
2007-01-01
Woodpeckers possess mechanisms protecting the eye from shaking/impact. Mechanisms available to woodpeckers but not humans may help explain some eye injuries in Shaken Baby syndrome (SBS). Gross dissection and histologic examination of eyes and orbits of seven woodpeckers. All birds showed restricted axial globe movement due to the tight fit within the orbit and fascial connections between the orbital rim and sclera. The sclera was reinforced with cartilage and bone, the optic nerve lacked redundancy, and the vitreous lacked attachments to the posterior pole retina. Woodpecker eyes differ from human infants by an inability of the globe to move axially in the orbit, the sclera to deform, and the vitreous to shear the retina. These findings support current hypotheses that abusive acceleration-deceleration-induced ocular injury in human infants may be related to translation of vitreous within the globe and the globe within the orbit. The woodpecker presents a natural model resistant to mechanical forces that have some similarity to SBS.
Chen, Ko-Hua; Li, Mei-Jane; Cheng, Wen-Ting; Balic-Zunic, Tonci; Lin, Shan-Yang
2009-02-01
Raman microspectroscopy was first used to determine the composition of a calcified plaque located at the pterygium-excision site of a 51-year-old female patient's left nasal sclera after surgery. It was unexpectedly found that the Raman spectrum of the calcified sample at 1149, 1108, 1049, 756, 517, 376 and 352/cm was similar to the Raman spectrum of monoclinic form of calcium pyrophosphate dihydrate (CPPD) crystal, but differed from the Raman spectrum of triclinic form of CPPD. An additional peak at 958/cm was also observed in the Raman spectrum of the calcified plaque, which was identical to the characteristic peak at 958/cm of hydroxyapatite (HA). This is the first study to report the spectral biodiagnosis of both monoclinic CPPD and HA co-deposited in the calcified plaque of a patient with sclera dystrophic calcification using Raman microspectroscopy.
Chen, Ko-Hua; Li, Mei-Jane; Cheng, Wen-Ting; Balic-Zunic, Tonci; Lin, Shan-Yang
2009-01-01
Raman microspectroscopy was first used to determine the composition of a calcified plaque located at the pterygium-excision site of a 51-year-old female patient's left nasal sclera after surgery. It was unexpectedly found that the Raman spectrum of the calcified sample at 1149, 1108, 1049, 756, 517, 376 and 352/cm was similar to the Raman spectrum of monoclinic form of calcium pyrophosphate dihydrate (CPPD) crystal, but differed from the Raman spectrum of triclinic form of CPPD. An additional peak at 958/cm was also observed in the Raman spectrum of the calcified plaque, which was identical to the characteristic peak at 958/cm of hydroxyapatite (HA). This is the first study to report the spectral biodiagnosis of both monoclinic CPPD and HA co-deposited in the calcified plaque of a patient with sclera dystrophic calcification using Raman microspectroscopy. PMID:19200254
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sobol', E N; Vorobieva, N N; Omel'chenko, A I
A new approach is proposed for correcting the eye refraction by controlled variation of the mechanical properties of the sclera and cornea upon nondestructive laser heating. Experimental ex vivo studies of rabbit and pig eyes show that laser-induced local denaturation of the sclera changes the refraction of the cornea by 3 diopters on the average, and the subsequent nondestructive irradiation of the cornea increases its plasticity, which leads to a further increase in its radius of curvature and a decrease in refraction down to 7 diopters.
New Technique of Exposed Glaucoma Drainage Tube Repair: Report of a Case.
Berezina, Tamara L; Fechtner, Robert D; Cohen, Amir; Kim, Eliott E; Chu, David S
2015-01-01
We present the case of successful repair of an exposed glaucoma drainage tube by cornea graft fixation with tissue adhesive, and without subsequent coverage by adjacent conjunctiva or donor tissues. Patient with history of keratoglobus with thin cornea and sclera, and phthisical contralateral eye, underwent three unsuccessful corneal grafts followed by Boston type 1 keratoprosthesis in the right eye. Ahmed drainage device with sclera patch graft was implanted to control the intraocular pressure. Two years later the tube eroded through sclera graft and conjunctiva. Repair was performed by covering the tube with a corneal patch graft secured by tissue adhesive after the conjunctiva in this area was dissected away. The cornea graft was left uncovered due to fragility of adjacent conjunctiva. The healing of ocular and graft surfaces was complete prior to the 1 month follow-up. Conjunctival epithelium covered the corneal patch graft. At 12 months follow-up, the graft and the tube remained stable. Our report suggests that corneal patch graft fixation to the sclera by means of tissue adhesive, without closing the conjunctiva, can be considered as an effective alternative surgical approach for managing exposed glaucoma drainage tube, accompanied by adjacent conjunctiva tissue deficiency. How to cite this article: Berezina TL, Fechtner RD, Cohen A, Kim EE, Chu DS. New Technique of Exposed Glaucoma Drainage Tube Repair: Report of a Case. J Curr Glaucoma Pract 2015;9(2):62-64.
Coherent anti-stokes Raman scattering (CARS) microscopy: a novel technique for imaging the retina.
Masihzadeh, Omid; Ammar, David A; Kahook, Malik Y; Lei, Tim C
2013-05-01
To image the cellular and noncellular structures of the retina in an intact mouse eye without the application of exogenous fluorescent labels using noninvasive, nondestructive techniques. Freshly enucleated mouse eyes were imaged using two nonlinear optical techniques: coherent anti-Stokes Raman scattering (CARS) and two-photon autofluorescence (TPAF). Cross sectional transverse sections and sequential flat (en face) sagittal sections were collected from a region of sclera approximately midway between the limbus and optic nerve. Imaging proceeded from the surface of the sclera to a depth of ∼60 μm. The fluorescent signal from collagen fibers within the sclera was evident in the TPAF channel; the scleral collagen fibers showed no organization and appeared randomly packed. The sclera contained regions lacking TPAF and CARS fluorescence of ∼3 to 15 μm in diameter that could represent small vessels or scleral fibroblasts. Intense punctate CARS signals from the retinal pigment epithelial layer were of a size and shape of retinyl storage esters. Rod outer segments could be identified by the CARS signal from their lipid-rich plasma membranes. CARS microscopy can be used to image the outer regions of the mammalian retina without the use of a fluorescent dye or exogenously expressed recombinant protein. With technical advancements, CARS/TPAF may represent a new avenue for noninvasively imaging the retina and might complement modalities currently used in clinical practice.
Ultrastructure of the extracellular matrix of bovine dura mater, optic nerve sheath and sclera.
Raspanti, M; Marchini, M; Della Pasqua, V; Strocchi, R; Ruggeri, A
1992-01-01
The sclera, the outermost sheath of the optic nerve and the dura mater have been investigated histologically and ultrastructurally. Although these tissues appear very similar under the light microscope, being dense connective tissues mainly composed of collagen bundles and a limited amount of cells and elastic fibres, they exhibit subtle differences on electron microscopy. In the dura and sclera collagen appears in the form of large, nonuniform fibrils, similar to those commonly found in tendons, while in the optic nerve sheath the fibrils appear smaller and uniform, similar to those commonly observed in reticular tissues, vessel walls and skin. Freeze-fracture also reveals these fibrils to have different subfibrillar architectures, straight or helical, which correspond to 2 distinct forms of collagen fibril previously described (Raspanti et al. 1989). The other extracellular matrix components also vary with the particular collagen fibril structure. Despite their common embryological derivation, the dura mater, optic nerve sheath and sclera exhibit diversification of their extracellular matrix consistent with the mechanical loads to which these tissues are subjected. Our observations indicate that the outermost sheath of the optic nerve resembles the epineurium of peripheral nerves rather than the dura to which it is commonly likened. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:1295858
Nguyen, Cathy; Cone, Frances E.; Nguyen, Thao D.; Coudrillier, Baptiste; Pease, Mary E.; Steinhart, Matthew R.; Oglesby, Ericka N.; Jefferys, Joan L.; Quigley, Harry A.
2013-01-01
Purpose. To study anatomical changes and mechanical behavior of the sclera in mice with experimental glaucoma by comparing CD1 to B6 mice. Methods. Chronic experimental glaucoma for 6 weeks was produced in 2- to 4-month-old CD1 (43 eyes) and B6 mice (42 eyes) using polystyrene bead injection into the anterior chamber with 126 control CD1 and 128 control B6 eyes. Intraocular pressure (IOP) measurements were made with the TonoLab at baseline and after bead injection. Axial length and scleral thickness were measured after sacrifice in the CD1 and B6 animals and compared to length data from 78 eyes of DBA/2J mice. Inflation testing of posterior sclera was conducted, and circumferential and meridional strain components were determined from the displacement response. Results. Experimental glaucoma led to increases in axial length and width by comparison to fellow eyes (6% in CD1 and 10% in B6; all P < 0.03). While the peripapillary sclera became thinner in both mouse types with glaucoma, the remainder of the sclera uniformly thinned in CD1, but thickened in B6. Peripapillary sclera in CD1 controls had significantly greater temporal meridional strain than B6 and had differences in the ratios of meridional to effective circumferential strain from B6 mice. In both CD1 and B6 mice, exposure to chronic IOP elevation resulted in stiffer pressure–strain responses for both the effective circumferential and meridional strains (multivariable regression model, P = 0.01–0.03). Conclusions. Longer eyes, greater scleral strain in some directions at baseline, and generalized scleral thinning after glaucoma were characteristic of CD1 mice that have greater tendency to retinal ganglion cell damage than B6 mice. Increased scleral stiffness after glaucoma exposure in mice mimics findings in monkey and human glaucoma eyes. PMID:23404116
Influence of asymmetric donor-receiver ion concentration upon transscleral iontophoretic transport.
Li, S Kevin; Zhang, Yanhui; Zhu, Honggang; Higuchi, William I; White, Henry S
2005-04-01
Recent in vitro and in vivo studies have suggested transscleral iontophoresis as a means for non-invasive drug delivery to the eye. However, there remains a lack of information of the iontophoretic transport behavior of the sclera. The objective of the present study was to investigate the effects of permeant concentration upon transscleral iontophoretic transport. Constant current direct current (DC) iontophoresis was conducted with rabbit sclera in vitro at permeant concentration ranging from 0.015 to 1.0 M in the donor chamber without background electrolyte at 0.4-4 mA (current density: 2-20 mA/cm2). PBS (0.15 M) was the receiver solution. Salicylate (SA) and tetraethylammonium (TEA) were the model ionic permeants, and mannitol was the neutral probe permeant. Conductivity experiments of SA and TEA solutions were performed to determine the effects of ion concentration upon SA and TEA electromobilities. Model simulations were carried out and compared with the experimental data. It was found that the fluxes of the ionic permeants increased linearly with the electric current but were relatively independent of their donor concentrations. Electric field-induced convective solvent flow (electroosmosis) in the sclera was observed to be from the anode to cathode, suggesting that the sclera is net negatively charge at neutral pH. For the studied permeants, electrophoresis was the main transport enhancing mechanism with electroosmosis as a secondary effect. No significant interaction between the permeants and sclera was observed that significantly altered electroosmosis in the membrane. Under the asymmetric donor and receiver conditions, the transference of the permeants could not be predicted by the concentrations of the ions in the donor and receiver chambers with the assumption of constant electric field in the membrane. The membrane ion concentrations were different from those in the chambers due to the requirement of charge neutrality in the membrane. Copyright (c) 2005 Wiley-Liss, Inc.
[Technique for removing donor sclera by eyeball extrusion].
González Del Valle, F; Álvarez Portela, M; Lara Medina, J; Celis Sánchez, J; Barrajón Rodríguez, A
2012-09-01
To describe a surgery technique for removing donor sclera tissue after corneo-scleral button excision. The extrusion technique is easy to perform. It allows the complete scleral extraction its total clean up to be performed, as well as making easier to isolate the retina and uveal tissue. This technique could have an important role in the anatomical and morphological study of ocular structures. Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.
Scleral fibroblast response to experimental glaucoma in mice
Tezel, Gülgün; Cone-Kimball, Elizabeth; Steinhart, Matthew R.; Jefferys, Joan; Pease, Mary E.; Quigley, Harry A.
2016-01-01
Purpose To study the detailed cellular and molecular changes in the mouse sclera subjected to experimental glaucoma. Methods Three strains of mice underwent experimental bead-injection glaucoma and were euthanized at 3 days and 1, 3, and 6 weeks. Scleral protein expression was analyzed with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) using 16O/18O labeling for quantification in 1- and 6-week tissues. Sclera protein samples were also analyzed with immunoblotting with specific antibodies to selected proteins. The proportion of proliferating scleral fibroblasts was quantified with Ki67 and 4’,6-diamidino-2-phenylindole (DAPI) labeling, and selected proteins were studied with immunohistochemistry. Results Proteomic analysis showed increases in molecules involved in integrin-linked kinase signaling and actin cytoskeleton signaling pathways at 1 and 6 weeks after experimental glaucoma. The peripapillary scleral region had more fibroblasts than equatorial sclera (p=0.001, n=217, multivariable regression models). There was a sixfold increase in proliferating fibroblasts in the experimental glaucoma sclera at 1 week and a threefold rise at 3 and 6 weeks (p=0.0005, univariate regression). Immunoblots confirmed increases for myosin, spectrin, and actinin at 1 week after glaucoma. Thrombospondin-1 (TSP-1), HINT1, vimentin, actinin, and α-smooth muscle actin were increased according to immunohistochemistry. Conclusions Scleral fibroblasts in experimental mouse glaucoma show increases in actin cytoskeleton and integrin-related signaling, increases in cell division, and features compatible with myofibroblast transition. PMID:26900327
Coherent Anti-Stokes Raman Scattering (CARS) Microscopy: A Novel Technique for Imaging the Retina
Masihzadeh, Omid; Ammar, David A.; Kahook, Malik Y.; Lei, Tim C.
2013-01-01
Purpose. To image the cellular and noncellular structures of the retina in an intact mouse eye without the application of exogenous fluorescent labels using noninvasive, nondestructive techniques. Methods. Freshly enucleated mouse eyes were imaged using two nonlinear optical techniques: coherent anti-Stokes Raman scattering (CARS) and two-photon autofluorescence (TPAF). Cross sectional transverse sections and sequential flat (en face) sagittal sections were collected from a region of sclera approximately midway between the limbus and optic nerve. Imaging proceeded from the surface of the sclera to a depth of ∼60 μm. Results. The fluorescent signal from collagen fibers within the sclera was evident in the TPAF channel; the scleral collagen fibers showed no organization and appeared randomly packed. The sclera contained regions lacking TPAF and CARS fluorescence of ∼3 to 15 μm in diameter that could represent small vessels or scleral fibroblasts. Intense punctate CARS signals from the retinal pigment epithelial layer were of a size and shape of retinyl storage esters. Rod outer segments could be identified by the CARS signal from their lipid-rich plasma membranes. Conclusions. CARS microscopy can be used to image the outer regions of the mammalian retina without the use of a fluorescent dye or exogenously expressed recombinant protein. With technical advancements, CARS/TPAF may represent a new avenue for noninvasively imaging the retina and might complement modalities currently used in clinical practice. PMID:23580484
Biomechanical Changes in the Sclera of Monkey Eyes Exposed to Chronic IOP Elevations
Girard, Michaël J. A.; Suh, J.-K. Francis; Bottlang, Michael; Burgoyne, Claude F.
2011-01-01
Purpose. To characterize scleral biomechanics in both eyes of eight monkeys in which chronic intraocular pressure (IOP) elevation was induced in one eye. Methods. Each posterior sclera was mounted on a pressurization apparatus, IOP was elevated from 5 to 45 mm Hg while the 3D displacements of the scleral surface were measured by speckle interferometry. Finite element (FE) models of each scleral shell were constructed that incorporated stretch-induced stiffening and multidirectionality of the collagen fibers. FE model predictions were then iteratively matched to experimental displacements to extract unique sets of scleral biomechanical properties. Results. For all eyes, the posterior sclera exhibited inhomogeneous, anisotropic, nonlinear biomechanical behavior. Biomechanical changes caused by chronic IOP elevation were complex and specific to each subject. Specifically: (1) Glaucomatous eyes in which the contralateral normal eyes displayed large modulus or thickness were less prone to biomechanical changes; (2) glaucomatous scleral modulus associated with an IOP of 10 mm Hg decreased (when compared with that of the contralateral normal) after minimal chronic IOP elevation; (3) glaucomatous scleral modulus associated with IOPs of 30 and 45 mm Hg increased (when compared with that of the contralateral normal) after moderate IOP elevation; and (4) FE-based estimates of collagen fiber orientation demonstrated no change in the glaucomatous eyes. Conclusions. Significant stiffening of the sclera follows exposure to moderate IOP elevations in most eyes. Scleral hypercompliance may precede stiffening or be a unique response to minimal chronic IOP elevation in some eyes. These biomechanical changes are likely to be the result of scleral extracellular matrix remodeling. PMID:21519033
Ghosn, Mohamad G; Tuchin, Valery V; Larin, Kirill V
2007-06-01
Noninvasive functional imaging, monitoring, and quantification of analytes transport in epithelial ocular tissues are extremely important for therapy and diagnostics of many eye diseases. In this study the authors investigated the capability of optical coherence tomography (OCT) for noninvasive monitoring and quantification of diffusion of different analytes in sclera and cornea of rabbit eyes. A portable time-domain OCT system with wavelength of 1310 +/- 15 nm, output power of 3.5 mW, and resolution of 25 mum was used in this study. Diffusion of different analytes was monitored and quantified in rabbit cornea and sclera of whole eyeballs. Diffusion of water, metronidazole (0.5%), dexamethasone (0.2%), ciprofloxacin (0.3%), mannitol (20%), and glucose solution (20%) were examined, and their permeability coefficients were calculated by using OCT signal slope and depth-resolved amplitude methods. Permeability coefficients were calculated as a function of time and tissue depth. For instance, mannitol was found to have a permeability coefficient of (8.99 +/- 1.43) x 10(-6) cm/s in cornea and (6.18 +/- 1.08) x 10(-6) cm/s in sclera. The permeability coefficient of drugs with small concentrations (where water was the major solvent) was found to be in the range of that of water in the same tissue type, whereas permeability coefficients of higher concentrated solutions varied significantly. Results suggest that the OCT technique might be a powerful tool for noninvasive diffusion studies of different analytes in ocular tissues. However, additional methods of OCT signal acquisition and processing are required to study the diffusion of agents of small concentrations.
Kaufman, Herbert E; Insler, Michael S; Ibrahim-Elzembely, Hosan A; Kaufman, Stephen C
2003-11-01
To determine whether a fibrin adhesive can facilitate the performance of sutureless lamellar keratoplasty and attachment of amnion to bare sclera. Prospective, noncomparative case series. Six patients, 5 of whom underwent lamellar keratoplasty and 1 who received an amniotic patch of the sclera and cornea. Institutional review board approval was not required for these therapeutic treatments. In 5 patients, the epithelium was removed from the corneal surface, a free cap, 200- micro m thick, was cut with a microkeratome, and a human fibrin tissue adhesive (Tisseel VH Fibrin Sealant; Baxter Healthcare Corporation, Glendale, CA) was applied to the cut surface of the corneal stroma. A 200- micro m thick, microkeratome-cut lamellar graft was placed in the stromal bed without sutures, and a bandage soft contact lens was applied. The lens was left in place for 1 week and then removed. In 1 patient, the adhesive was applied to bare sclera for attachment of amniotic membrane after removal of a conjunctival melanosis. All patients were followed up for 3 months after surgery. Tissue adhesion, corneal clarity, and visual acuity. All 5 lamellar grafts healed and remained clear, although final visual acuity varied with visual potential and astigmatism. The amniotic membrane graft also adhered well to the bare sclera. The fibrin adhesive provided satisfactory attachment without sutures for lamellar keratoplasty and amniotic patching. It should be effective for sealing of clear cornea incisions, LASIK flaps, and conjunctival and skin grafts. An adhesive that has been designed specifically for ophthalmic applications and is more convenient to use would be desirable.
NASA Astrophysics Data System (ADS)
Sugiyama, S.; Hong, Y.-J.; Kasaragod, D.; Makita, S.; Miura, M.; Ikuno, Y.; Yasuno, Y.
2016-03-01
Quantitative evaluation of optical properties of choroid and sclera are performed by multifunctional optical coherence tomography. Five normal eyes, five glaucoma eyes and one choroidal atrophy eye are examined. The refractive error was found to be correlated with choroidal birefringence, polarization uniformity, and flow in addition to scleral birefringence among normal eyes. The significant differences were observed between the normal and the glaucoma eyes, as for choroidal polarization uniformity, flow and scleral birefringence. An automatic segmentation algorithm of retinal pigment epithelium and chorioscleral interface based on multifunctional signals is also presented.
Yoo, Tae Keun; Han, Sueng-Han; Han, Jinu
2017-12-01
To determine the efficacy of a biodegradable Ologen (Aeon Astron Europe BV, Leiden, The Netherlands) collagen matrix in reducing the blue color change due to exposed thinned sclera after strabismus surgery. Fourteen patients with intermittent exotropia undergoing symmetric bilateral lateral rectus recession surgery were included in this prospective, randomized, paired-eye controlled study. In each patient, Ologen was implanted at the original rectus insertion site in one randomly selected eye; the other eye underwent conventional surgery. Ologen was inserted under the conjunctiva without suturing, covering the muscle insertion site. Conjunctival color change was analyzed using computer-based image analysis immediately and 1 week, 1 month, and 3 months postoperatively. Slit-lamp photographs of each eye were evaluated using contrast limited adaptive histogram equalization (CLAHE), Canny edge, and the RGB (red-green-blue) model. Secondary outcomes were conjunctival and sclera thickness 3 months postoperatively determined by anterior segment optical coherence tomography. Immediately and 1 week postoperatively all color models showed no significant differences between Ologen-implanted and control eyes. Three months postoperatively, Ologen-implanted eyes exhibited significantly lower CLAHE (P = 0.041) and RGB model blue color (P = 0.008) values than control eyes. Canny edge (P = 0.061) and RGB model red color (P = 0.152) values did not differ between eyes. Conjunctival stroma and episcleral complex thickness was greater in Ologen-implanted eyes than in controls (P = 0.001). Blue color change was significantly less noticeable in Ologen-implanted eyes than in controls. Thus, Ologen implantation helps prevent visible blue sclera at the original rectus insertion site after lateral rectus recession. Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.
Effects of Peripapillary Scleral Stiffening on the Deformation of the Lamina Cribrosa
Coudrillier, Baptiste; Campbell, Ian C.; Read, A. Thomas; Geraldes, Diogo M.; Vo, Nghia T.; Feola, Andrew; Mulvihill, John; Albon, Julie; Abel, Richard L.; Ethier, C. Ross
2016-01-01
Purpose Scleral stiffening has been proposed as a treatment for glaucoma to protect the lamina cribrosa (LC) from excessive intraocular pressure–induced deformation. Here we experimentally evaluated the effects of moderate stiffening of the peripapillary sclera on the deformation of the LC. Methods An annular sponge, saturated with 1.25% glutaraldehyde, was applied to the external surface of the peripapillary sclera for 5 minutes to stiffen the sclera. Tissue deformation was quantified in two groups of porcine eyes, using digital image correlation (DIC) or computed tomography imaging and digital volume correlation (DVC). In group A (n = 14), eyes were subjected to inflation testing before and after scleral stiffening. Digital image correlation was used to measure scleral deformation and quantify the magnitude of scleral stiffening. In group B (n = 5), the optic nerve head region was imaged using synchrotron radiation phase-contrast microcomputed tomography (PC μCT) at an isotropic spatial resolution of 3.2 μm. Digital volume correlation was used to compute the full-field three-dimensional deformation within the LC and evaluate the effects of peripapillary scleral cross-linking on LC biomechanics. Results On average, scleral treatment with glutaraldehyde caused a 34 ± 14% stiffening of the peripapillary sclera measured at 17 mm Hg and a 47 ± 12% decrease in the maximum tensile strain in the LC measured at 15 mm Hg. The reduction in LC strains was not due to cross-linking of the LC. Conclusions Peripapillary scleral stiffening is effective at reducing the magnitude of biomechanical strains within the LC. Its potential and future utilization in glaucoma axonal neuroprotection requires further investigation. PMID:27183053
Mertz, J R; Wallman, J
2000-04-01
Research over the past two decades has shown that the growth of young eyes is guided by vision. If near- or far-sightedness is artificially imposed by spectacle lenses, eyes of primates and chicks compensate by changing their rate of elongation, thereby growing back to the pre-lens optical condition. Little is known about what chemical signals might mediate between visual effects on the retina and alterations of eye growth. We present five findings that point to choroidal retinoic acid possibly being such a mediator. First, the chick choroid can convert retinol into all-trans-retinoic acid at the rate of 11 +/- 3 pmoles mg protein(-1) hr(-1), compared to 1.3 +/- 0.3 for retina/RPE and no conversion for sclera. Second, those visual conditions that cause increased rates of ocular elongation (diffusers or negative lens wear) produce a sharp decrease in all-trans-retinoic acid synthesis to levels barely detectable with our assay. In contrast, visual conditions which result in decreased rates of ocular elongation (recovery from diffusers or positive lens wear) produce a four- to five-fold increase in the formation of all-trans-retinoic acid. Third, the choroidal retinoic acid is found bound to a 28-32 kD protein. Fourth, a large fraction of the choroidal retinoic acid synthesized in culture is found in a nucleus-enriched fraction of sclera. Finally, application of retinoic acid to cultured sclera at physiological concentrations produced an inhibition of proteoglycan production (as assessed by measuring sulfate incorporation) with a EC50 of 8 x 10(-7) M. These results show that the synthesis of choroidal retinoic acid is modulated by those visual manipulations that influence ocular elongation and that this retinoic acid may reach the sclera in concentrations adequate to modulate scleral proteoglycan formation.
Tarutta, E P; Maksimova, M V; Kruzhkova, G V; Khodzhabekian, N V; Markosian, G A
2013-01-01
Prognostic value of acoustic density of sclera (ADS) is studied in development of peripheral vitreochorioretinal degenerations (PVCRD) in myopia. Children aged 8-10 years old with noncomplicated high and moderate myopia were divided into two groups after ADS measurement: 1 with ADS < or = 39dB - unfavorable prognosis, 2 with ADS >39dB - favorable prognosis. Follow-up during 10 years with examinations twice a year confirmed prognosis accuracy: in the 1st group PVCRD developed 2.5 times as often as in the 2nd group (64.6 and 25.6% respectively).
Sclera-directed knot technique for securing an encircling band in retinal surgery.
Bartov, E; Ginsburg, L H; Ashkenazi, I; Treister, G
1991-10-01
The protruding ends of sutures used to secure the ends of the silicone rubber band placed during many retinal surgical procedures may cause postsurgical irritation, since with presently used suturing techniques, the knot of the suture remains on top of the band, facing the conjunctiva. We describe a suturing technique which, by inverting the band when suturing its ends and then allowing the band to return to its original position, places the knot on the undersurface of the band, against the sclera. Thus, no protruding suture ends are left facing the conjunctiva and the irritation resulting from such a protrusion is averted.
Complications of cosmetic eye whitening.
Tran, Ann Q; Hoppener, Catherine; Venkateswaran, Nandini; Choi, Daniel S; Lee, Wendy W
2017-09-01
Introduced in 2008 and subsequently popularized in South Korea, cosmetic eye whitening has been offered as a treatment of chronic conjunctival hyperemia. Patients undergo conjunctivectomy with topical mitomycin C (MMC) 0.02% application to achieve a whitened appearance from bleaching of avascular sclera. Much speculation has arisen from this procedure given the limited available evidence on its efficacy and safety. A literature search was performed to review common complications of cosmetic eye whitening, including chronic conjunctival epithelial defects, scleral thinning, avascular zones in the sclera, dry eye syndrome, and diplopia requiring strabismus surgery. Informing the general public of the risks of this procedure is of great importance for dermatologists and other cosmetic surgeons.
Quigley, Harry A
2015-01-01
Glaucoma, the second most common cause of world blindness, results from loss of retinal ganglion cells (RGC). RGC die as a consequence of injury to their axons, as they pass through the transition between the environment within the eye and that of the retrobulbar optic nerve, as they course to central visual centers. At the optic nerve head (ONH), axonal transport becomes abnormal, at least in part due to the effect of strain induced by intraocular pressure (IOP) on the sclera and ONH. Animal glaucoma models provide the ability to study how alterations in ocular connective tissues affect this pathological process. New therapeutic interventions are being investigated to mitigate glaucoma blindness by modifying the remodeling of ocular tissues in glaucoma. Some genetically altered mice are resistant to glaucoma damage, while treatment of the sclera with cross-linking agents makes experimental mouse glaucoma damage worse. Inhibition of transforming growth factor β activity is strikingly protective. Treatments that alter the response of ocular connective tissues to IOP may be effective in protecting those with glaucoma from vision loss. © 2015 Elsevier B.V. All rights reserved.
Lim, Wan'E; Kwan, Jia Lin; Goh, Liang Kee; Beuerman, Roger W; Barathi, Veluchamy A
2012-01-01
The aim of this study was to identify the genes and pathways underlying the growth of the mouse sclera during postnatal development. Total RNA was isolated from each of 30 single mouse sclera (n=30, 6 sclera each from 1-, 2-, 3-, 6-, and 8-week-old mice) and reverse-transcribed into cDNA using a T7-N(6) primer. The resulting cDNA was fragmented, labeled with biotin, and hybridized to a Mouse Gene 1.0 ST Array. ANOVA analysis was then performed using Partek Genomic Suite 6.5 beta and differentially expressed transcript clusters were filtered based on a selection criterion of ≥ 2 relative fold change at a false discovery rate of ≤ 5%. Genes identified as involved in the main biologic processes during postnatal scleral development were further confirmed using qPCR. A possible pathway that contributes to the postnatal development of the sclera was investigated using Ingenuity Pathway Analysis software. The hierarchical clustering of all time points showed that they did not cluster according to age. The highest number of differentially expressed transcript clusters was found when week 1 and week 2 old scleral tissues were compared. The peroxisome proliferator- activated receptor gamma coactivator 1-alpha (Ppargc1a) gene was found to be involved in the networks generated using Ingenuity Pathway Studio (IPA) from the differentially expressed transcript cluster lists of week 2 versus 1, week 3 versus 2, week 6 versus 3, and week 8 versus 6. The gene expression of Ppargc1a varied during scleral growth from week 1 to 2, week 2 to 3, week 3 to 6, and week 6 to 8 and was found to interact with a different set of genes at different scleral growth stages. Therefore, this indicated that Ppargc1a might play a role in scleral growth during postnatal weeks 1 to 8. Gene expression of eye diseases should be studied as early as postnatal weeks 1-2 to ensure that any changes in gene expression pattern during disease development are detected. In addition, we propose that Ppargc1a might play a role in regulating postnatal scleral development by interacting with a different set of genes at different scleral growth stages.
Evaluation of gene expression profiles and pathways underlying postnatal development in mouse sclera
Lim, Wan’E.; Kwan, Jia Lin; Goh, Liang Kee; Beuerman, Roger W.
2012-01-01
Purpose The aim of this study was to identify the genes and pathways underlying the growth of the mouse sclera during postnatal development. Methods Total RNA was isolated from each of 30 single mouse sclera (n=30, 6 sclera each from 1-, 2-, 3-, 6-, and 8-week-old mice) and reverse-transcribed into cDNA using a T7-N6 primer. The resulting cDNA was fragmented, labeled with biotin, and hybridized to a Mouse Gene 1.0 ST Array. ANOVA analysis was then performed using Partek Genomic Suite 6.5 beta and differentially expressed transcript clusters were filtered based on a selection criterion of ≥2 relative fold change at a false discovery rate of ≤5%. Genes identified as involved in the main biologic processes during postnatal scleral development were further confirmed using qPCR. A possible pathway that contributes to the postnatal development of the sclera was investigated using Ingenuity Pathway Analysis software. Results The hierarchical clustering of all time points showed that they did not cluster according to age. The highest number of differentially expressed transcript clusters was found when week 1 and week 2 old scleral tissues were compared. The peroxisome proliferator- activated receptor gamma coactivator 1-alpha (Ppargc1a) gene was found to be involved in the networks generated using Ingenuity Pathway Studio (IPA) from the differentially expressed transcript cluster lists of week 2 versus 1, week 3 versus 2, week 6 versus 3, and week 8 versus 6. The gene expression of Ppargc1a varied during scleral growth from week 1 to 2, week 2 to 3, week 3 to 6, and week 6 to 8 and was found to interact with a different set of genes at different scleral growth stages. Therefore, this indicated that Ppargc1a might play a role in scleral growth during postnatal weeks 1 to 8. Conclusions Gene expression of eye diseases should be studied as early as postnatal weeks 1–2 to ensure that any changes in gene expression pattern during disease development are detected. In addition, we propose that Ppargc1a might play a role in regulating postnatal scleral development by interacting with a different set of genes at different scleral growth stages. PMID:22736935
Study on establishment and mechanics application of finite element model of bovine eye.
Cui, Yan-Hui; Huang, Ju-Fang; Cheng, Si-Ying; Wei, Wei; Shang, Lei; Li, Na; Xiong, Kun
2015-08-13
Glaucoma mainly induced by increased intraocular pressure (IOP), it was believed that the pressure that wall of eyeball withstands were determined by material properties of the tissue and stereoscopic geometry of the eyeball. In order to study the pressure changes in different parts of interior eyeball wall, it is necessary to develop a novel eye ball FEM with more accurate geometry and material properties. Use this model to study the stress changes in different parts of eyeball, especially the lamina cribrosa (LC) under normal physiological and pathological IOP, and provide a mathematical model for biomechanical studies of selected retinal ganglion cells (RGCs) death. (1) Sclera was cut into 3.8-mm wide, 14.5-mm long strips, and cornea was cut into 9.5-mm-wide and 10-mm-long strips; (2) 858 Mini BionixII biomechanical loading instrument was used to stretch sclera and cornea. The stretching rate for sclera was 0.3 mm/s, 3 mm/s, 30 mm/s, 300 mm/s; and for cornea were 0.3 mm/s and 30 mm/s. The deformation-stress curve was recorded; (3) Naso-temporal and longitudinal distance of LC were measured; (4) Micro-CT was used to accurately scan fresh bovine eyes and obtain the geometrical image and data to establish bovine eye model. 3-D reconstruction was performed using these images and data to work out the geometric shape of bovine eye; (5) IOP levels for eyeball FEM was set and the inner wall of eyeball was used taken as load-bearing part. Simulated eyeball FE modeling was run under the IOP level of 10 mmHg, 30 mmHg, 60 mmHg and 100 mmHg, and the force condition of different parts of eyeball was recorded under different IOP levels. (1) We obtained the material parameters more in line with physiological conditions and established a more realistic eyeball model using reversed engineering of parameters optimization method to calculate the complex nonlinear super-elastic and viscoelastic parameters more accurately; (2) We observed the following phenomenon by simulating increased pressure using FEM: as simulative IOP increased, the stress concentration scope on the posterior half of sclera became narrower; in the meantime, the stress-concentration scope on the anterior half of scleral gradually expanded, and the stress on the central part of LC is highest. As simulative IOP increased, stress-concentration scope on the posterior half of sclera gradually narrowed; in the meantime, the stress-concentration scope on the anterior half of sclera gradually expanded, and the stress on the LC is mainly concentrated in the central part, suggesting that IOP is mainly concentrated in the anterior part of the eyeball as it increases. This might provide a biomechanical evidence to explain why RGCs in peripheral part die earlier than RGCs in central part under HIOP.
NASA Astrophysics Data System (ADS)
Zalevsky, Zeev; Ilovitsh, Asaf; Beiderman, Yevgeny
2013-10-01
We present an approach allowing seeing objects that are hidden and that are not positioned in direct line of sight with security inspection cameras. The approach is based on inspecting the back reflections obtained from the cornea and the sclera of the eyes of people attending the inspected scene and which are positioned in front of the hidden objects we aim to image after performing proper calibration with point light source (e.g. a LED). The scene can be a forensic scene or for instance a casino in which the application is to see the cards of poker players seating in front of you.
Norton, Thomas T.
2007-01-01
Purpose The tree shrew model of refractive development is particularly useful because, like humans, tree shrews have a fibrous sclera. Selective changes in some candidate extracellular matrix proteins and mRNAs have been found in the sclera during the development of, and recovery from, induced myopia. We undertook a more neutral proteomic analysis using two-dimensional gel electrophoresis and mass spectrometry to identify scleral proteins that are differentially expressed during the development of, and recovery from, lens-induced myopia. Methods Five tree shrews (Tupaia glis belangeri) wore a monocular –5 D lens for 4 days, starting 24 days after natural eye opening. At the end of this time, all treated eyes had partially compensated for the lens and were –3.5±0.7 D (mean ± SEM) myopic relative to the untreated fellow control eyes. An additional five animals wore a –5 D lens for 11–13 days, followed by 4 days of recovery without the –5 D lens. The amount of recovery was 1.6±0.4 D. Scleral proteins from both groups were then isolated and resolved by two-dimensional gel electrophoresis and spots that were differentially expressed were identified by mass spectrometry. Results The scleral protein profile typically displayed ~700 distinct protein spots within the pH 5–8 range. Comparison of the treated-eye and control-eye scleras of the lens-compensation animals revealed five spots that were significantly differentially expressed in all five pairs of eyes; all were downregulated 1.2 to 1.7 fold in the treated eye. These proteins were identified as: pigment epithelium-derived factor (PEDF), procollagen I α1, procollagen I α2, and thrombospondin I (two spots). In the recovering eyes, the two thrombospondin I spots remained lower in abundance while PEDF and the procollagens were no longer downregulated. In addition, 78 kDa glucose-regulated protein (GRP 78), a member of the heat shock protein 70 family, was slightly upregulated 1.3 fold. Conclusions We found consistent results across animals that were of a magnitude consistent with the physiologically small changes to the focal plane of these eyes. Changes in collagen confirm previous findings, but downregulation of thrombospondin I adds detail to our understanding of the chain of signals that regulates scleral creep rate. The differential changes in PEDF and GRP 78 were not expected, based on previous studies, and demonstrate the utility of the proteomic approach in tree shrew sclera. PMID:17893659
Yancovitz, Molly; Anolik, Robert; Pomeranz, Miriam Keltz
2010-11-15
A 69-year-old woman presented with a 30-year history of lower back and large joint pain of the hips and shoulders. On examination blue-grey, pigmented macules were present over the cartilaginous portions of the ears and on the sclera. Past medical history included aortic stenosis. Urine homogentisic acid level was elevated, which is diagnostic for alkaptonuria. Alkaptonuria is an autosomal recessive disorder that results in deficiency of homogentisic acid oxidase and in the accumulation of homogentisic acid in connective tissue. Disease can result in blue-grey pigmentation of the cartilage, sclerae, face, and hands as well as severe arthropathy and cardiac valve disease. Treatment is limited at this time. Promising early reports of the use of nitisinone have prompted ongoing trials of this therapeutic agent.
A Review of Collagen Cross-Linking in Cornea and Sclera
Zhang, Xiao; Tao, Xiang-chen; Zhang, Jian; Li, Zhi-wei; Xu, Yan-yun; Wang, Yu-meng; Zhang, Chun-xiao; Mu, Guo-ying
2015-01-01
Riboflavin/UVA cross-linking is a technique introduced in the past decades for the treatment of keratoconus, keratectasia, and infectious keratitis. Its efficacy and safety have been investigated with clinical and laboratory studies since its first clinical application by Wollensak for the treatment of keratoconus. Although its complications are encountered during clinical practice, such as infection inducing risk, minimal invasion merits a further investigation on its future application in clinical practice. Recently, collagen cross-linking in sclera shows a promising prospect. In present study, we summarized the representative studies describing the clinical and laboratory application of collagen cross-linking published in past decades and provided our opinion on the positive and negative results of cross-linking in the treatment of ophthalmic disorders. PMID:25922758
Conditions associated with jaundice; Yellow skin and eyes; Skin - yellow; Icterus; Eyes - yellow; Yellow jaundice ... over time. Symptoms of jaundice commonly include: Yellow skin and the white part of the eyes (sclera) -- ...
Simulation model of an eyeball based on finite element analysis on a supercomputer.
Uchio, E; Ohno, S; Kudoh, J; Aoki, K; Kisielewicz, L T
1999-10-01
A simulation model of the human eye was developed. It was applied to the determination of the physical and mechanical conditions of impacting foreign bodies causing intraocular foreign body (IOFB) injuries. Modules of the Hypermesh (Altair Engineering, Tokyo, Japan) were used for solid modelling, geometric construction, and finite element mesh creation based on information obtained from cadaver eyes. The simulations were solved by a supercomputer using the finite element analysis (FEA) program PAM-CRASH (Nihon ESI, Tokyo, Japan). It was assumed that rupture occurs at a strain of 18.0% in the cornea and 6.8% in the sclera and at a stress of 9.4 MPa for both cornea and sclera. Blunt-shaped missiles were shot and set to impact on the surface of the cornea or sclera at velocities of 30 and 60 m/s, respectively. According to the simulation, the sizes of missile above which corneal rupture occurred at velocities of 30 and 60 m/s were 1.95 and 0.82 mm. The missile sizes causing scleral rupture were 0.95 and 0.75 mm at velocities of 30 and 60 m/s. These results suggest that this FEA model has potential usefulness as a simulation tool for ocular injury and it may provide useful information for developing protective measures against industrial and traffic ocular injuries.
Indentation and needle insertion properties of the human eye
Matthews, A; Hutnik, C; Hill, K; Newson, T; Chan, T; Campbell, G
2014-01-01
Purpose Characterization of the biomechanical properties of the human eye has a number of potential utilities. One novel purpose is to provide the basis for development of suitable tissue-mimicking material. The purpose of this study was to determine the indentation and needle insertion characteristics on human eye globes and tissue strips. Methods An indenter assessed the elastic response of human eye globes and tissue strips under increasing compressive loads. Needle insertion determined the force (N) needed to penetrate various areas of the eye wall. Results The results demonstrated that globes underwent slightly greater indentation at the midline than at the central cornea, and corneal strips indented twofold more than scleral strips, although neither difference was significant (P=0.400 and P=0.100, respectively). Significant differences were observed among various areas of needle insertion (P<0.001). Needle insertion through the anterior sclera (adjacent to the limbus) and posterior sclera (adjacent to the optic nerve) required the greatest amount of force (0.954 and 1.005 N, respectively). The force required to penetrate the central cornea (0.518 N) was significantly lower than all other areas except the midline sclera (0.700 N) Conclusion These data form the basis for further research into the development of a tissue-mimicking human eye construct with potential utility as a model for use in ophthalmology research and surgical teaching. PMID:24810571
Zhang, Zhen Huan; Pan, Meng Xin; Cai, Jia Tong; Weiland, James D; Chen, Kinon
2018-03-26
The purpose of this study is to measure, characterize, and compare the viscoelastic properties of the posterior eye of advanced dry age-related macular degeneration (AMD) patients, age-matched normal subjects, and pigs (3 groups). Ten horizontal and ten vertical strips of the macula retina and the underneath choroid and sclera were obtained for each group, respectively. They were examined by incremental stress-relaxation cycles in body-temperature saline. Mechanical response was characterized by the quasi-linear viscoelastic model. All the tissues were shown to be nonlinear viscoelastic. Stiffening and isotropization, increased relaxation, and softening and isotropization were found in AMD retina, choroid, and sclera, respectively, which are the mechanical features of the atherosclerotic process. The patients' medical records were in accordance with epidemiological studies indicating a relationship between the advanced AMD and atherosclerotic vascular disease (ASVD). Moreover, many differences were found between the viscoelastic properties of porcine and normal human retina, choroid, and sclera. The results suggest that AMD is associated with ASVD through a mechanism involving abnormal retinal, choroidal, and scleral mechanics similar to those seen in the atherosclerotic process. Moreover, researchers should be aware of mechanical differences when using porcine posterior eyes as a substitute for human posterior eyes. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2018. © 2018 Wiley Periodicals, Inc.
The Dynamic Sclera: Extracellular Matrix Remodeling in Normal Ocular Growth and Myopia Development
Harper, Angelica R.; Summers, Jody A.
2014-01-01
Myopia is a common ocular condition, characterized by excessive elongation of the ocular globe. The prevalence of myopia continues to increase, particularly among highly educated groups, now exceeding 80% in some groups. In parallel with the increased prevalence of myopia, are increases in associated blinding ocular conditions including glaucoma, retinal detachment and macular degeneration, making myopia a significant global health concern. The elongation of the eye is closely related to the biomechanical properties of the sclera, which in turn are largely dependent on the composition of the scleral extracellular matrix. Therefore an understanding of the cellular and extracellular events involved in the regulation of scleral growth and remodeling during childhood and young adulthood will provide future avenues for the treatment of myopia and its associated ocular complications. PMID:25819458
Retinoblastoma in the adolescent. Unusual clinical and histopathology findings.
Hernández-Ayuso, I; Ríos y Valles-Valles, D; Lome-Maldonado, C; Gómez-Leal, A; Rodríguez-Martínez, H A; Rodríguez-Reyes, A A
2016-03-01
A 17-year- old male with 2years history of an intraocular mass and progressive visual loss of the left eye. Spontaneous sclera rupture occurred during enucleation. Microscopic evaluation with H-E, PAS and immunohistochemistry (NSE, GAFP, SYN, CD99) revealed a small blue round cell malignant neoplasm with extensive necrosis and apoptosis. The optic nerve, ciliary body, choroid, anterior chamber, and sclera were infiltrated. SYN was positive and CD99 was negative in neoplastic cells, consistent with a poorly differentiated retinoblastoma. Retinoblastoma is the most frequent primary intraocular malignant tumour in childhood, but occasionally older patients can be affected. Immunohistochemistry is mandatory in poorly differentiated retinoblastomas. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.
Minocycline-induced hyperpigmentation of tympanic membrane, sclera, teeth, and pinna.
Reese, Stephen; Grundfast, Kenneth
2015-11-01
A 40-year-old woman was referred by her primary care physician for evaluation after a routine physical exam revealed bilateral brownish pigmentation of the tympanic membrane. Head and neck examination in the otolaryngology clinic revealed bluish hue of both sclera, teeth, and portions of her pinnae. A hearing test revealed bilateral mild sensorineural hearing loss. The patient had a history of taking minocycline for 14 years, and the hyperpigmentation that she had is known to be a rare complication of prolonged minocycline use. However, to our knowledge, this is the first case showing photographic evidence of minocycline-induced tympanic membrane hyperpigmentation. Minocycline-induced hyperpigmentation should be considered when a patient presents with brown or blue discoloration of the tympanic membrane. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.
The in vitro inflation response of mouse sclera.
Myers, Kristin M; Cone, Frances E; Quigley, Harry A; Gelman, Scott; Pease, Mary E; Nguyen, Thao D
2010-12-01
The purpose of this research was to develop a reliable and repeatable inflation protocol to measure the scleral inflation response of mouse eyes to elevations in intraocular pressure (IOP), comparing the inflation response exhibited by the sclera of younger and older C57BL/6 mice. Whole, enucleated eyes from younger (2 month) and older (11 month) C57BL/6 mice were mounted by the cornea on a custom fixture and inflated according to a load-unload, ramp-hold pressurization regimen via a cannula connected to a saline-filled programmable syringe pump. First, the tissue was submitted to three load-unload cycles from 6 mmHg to 15 mmHg at a rate of 0.25 mmHg/s with ten minutes of recovery between cycles. Next the tissue was submitted to a series of ramp-hold tests to measure the creep behavior at different pressure levels. For each ramp-hold test, the tissue was loaded from 6 mmHg to the set pressure at a rate of 0.25 mmHg/s and held for 30 min, and then the specimens were unloaded to 6 mmHg for 10 min. This sequence was repeated for set pressures of: 10.5, 15, 22.5, 30, 37.5, and 45 mmHg. Scleral displacement was measured using digital image correlation (DIC), and fresh scleral thickness was measured optically for each specimen after testing. For comparison, scleral thickness was measured on untested fresh tissue and epoxy-fixed tissue from age-matched animals. Comparing the apex displacement of the different aged specimens, the sclera of older animals had a statistically significant stiffer response to pressurization than the sclera of younger animals. The stiffness of the pressure-displacement response of the apex measured in the small-strain (6-15 mmHg) and the large-strain (37.5-45 mmHg) regime, respectively, were 287 ± 100 mmHg/mm and 2381 ± 191 mmHg/mm for the older tissue and 193 ± 40 mmHg/mm and 1454 ± 93 mmHg/mm for the younger tissue (Student t-test, p<0.05). The scleral thickness varied regionally, being thickest in the peripapillary region and thinnest at the equator. Fresh scleral thickness did not differ significantly by age in this group of animals. This study presents a reliable inflation test protocol to measure the mechanical properties of mouse sclera. The inflation methodology was sensitive enough to measure scleral response to changes in IOP elevations between younger and older C57BL/6 mice. Further, the specimen-specific scleral displacement profile and thickness measurements will enable future development of specimen-specific finite element models to analyze the inflation data for material properties. Copyright © 2010 Elsevier Ltd. All rights reserved.
... eyes, especially the eyelids, cornea, conjunctiva, sclera, and iris. Often a yellow dye (fluorescein) is used to ... lens on the front of the eye) Eyelids Iris (colored part of the eye between the cornea ...
21 CFR 886.3800 - Scleral shell.
Code of Federal Regulations, 2012 CFR
2012-04-01
... and proximal-cornea sclera for cosmetic or reconstructive purposes. An artificial eye is usually... controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this...
21 CFR 886.3800 - Scleral shell.
Code of Federal Regulations, 2014 CFR
2014-04-01
... and proximal-cornea sclera for cosmetic or reconstructive purposes. An artificial eye is usually... controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this...
21 CFR 886.3800 - Scleral shell.
Code of Federal Regulations, 2013 CFR
2013-04-01
... and proximal-cornea sclera for cosmetic or reconstructive purposes. An artificial eye is usually... controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this...
... white part of the eye (sclera), removes a piece of trabecular meshwork (eye tissue located around the ... tiny incision in the cornea and remove a piece of the trabecular meshwork to increase fluid drainage. ...
Karl, Anett; Makarov, Felix N; Koch, Christian; Körber, Nicole; Schuldt, Carsten; Krüger, Martin; Reichenbach, Andreas; Wiedemann, Peter; Bringmann, Andreas; Iseli, Hans Peter; Francke, Mike
2016-08-01
We aimed to determine the ultrastructural changes of collagen fibrils and cells in the rabbit sclera after scleral crosslinking using riboflavin and blue light of different intensities. Scleral crosslinking is known to increase scleral stiffness and may inhibit the axial elongation of progressive myopic eyes. The equatorial parts of the sclera of one eye of six adult albino rabbits were treated with topical riboflavin solution (0.5 %) followed by irradiation with blue light (200, 400, 650 mW/cm(2)) for 20 min. After 3 weeks, the ultrastructure of scleral cells and the abundance of small- (10-100 nm) and large-diameter (>100 nm) collagen fibrils in fibril bundles of different scleral layers were examined with electron microscopy. In the scleral stroma of control eyes, the thickness of collagen fibrils showed a bimodal distribution. The abundance of small-diameter collagen fibrils decreased from the inner towards the outer sclera, while the amount of large-diameter fibrils and the scleral collagen content did not differ between different stroma layers. Treatment with riboflavin and blue light at 200 mW/cm(2) did not induce ultrastructural changes of cells and collagen fibrils in the scleral stroma. Treatment with blue light of higher intensities induced scleral cell activation in a scleral layer-dependent manner. In addition, outer scleral layers contained phagocytes that engulfed collagen fibrils and erythrocytes. Blue light of the highest intensity induced a reduction of the scleral collagen content, a decreased abundance of large-diameter collagen fibrils, and an increased amount of small-diameter fibrils in the whole scleral stroma. The data indicate that in rabbits, scleral crosslinking with riboflavin and blue light of 200 mW/cm(2) for 20 min is relatively safe and does not induce ultrastructural alterations of scleral cells and of the collagen composition of the scleral stroma. Irradiation with blue light of intensities between 200 and 400 mW/cm(2) induces scleral cell activation, which may contribute to scleral scarring and stiffening. Higher intensities cause scleritis.
Zou, Leilei; Liu, Rui; Zhang, Xiaohui; Chu, Renyuan; Dai, Jinhui; Zhou, Hao
2014-01-01
Purpose Scleral remodeling is an important mechanism underlying the development of myopia. Atropine, an antagonist of G protein-coupled muscarinic receptors, is currently used as an off-label treatment for myopia. Regulator of G-protein signaling 2 (RGS2) functions as an intracellular selective inhibitor of muscarinic receptors. In this study we measured scleral RGS2 expression and scleral remodeling in an animal model of myopia in the presence or absence of atropine treatment. Methods Guinea pigs were assigned to four groups: normal (free of form deprivation), form deprivation myopia (FDM) for 4 weeks, FDM treated with saline, and FDM treated with atropine. Biometric measurements were then performed. RGS2 expression levels and scleral remodeling, including scleral thickness and collagen type I expression, were compared among the four groups. Results Compared with normal eyes and contralateral control eyes, the FDM eyes had the most prominent changes in refraction, axial length, and scleral remodeling, indicating myopia. There was no significant difference between control and normal eyes. Hematoxylin and eosin staining showed that the scleral thickness was significantly thinner in the posterior pole region of FDM eyes compared to normal eyes. Real-time PCR and western blot analysis showed a significant decrease in posterior scleral collagen type I mRNA and protein expression in the FDM eyes compared to the normal eyes. The FDM eyes also had increased levels of RGS2 mRNA and protein expression in the sclera. Atropine treatment attenuated the FDM-induced changes in refraction, axial length, and scleral remodeling. Interestingly, atropine treatment significantly increased collagen type I mRNA expression but decreased RGS2 mRNA and protein expression in the sclera of the FDM eyes. Conclusions We identified a significant RGS2 upregulation and collagen type I downregulation in the sclera of FDM eyes, which could be partially attenuated by atropine treatment. Our data suggest that targeting dysregulated RGS2 may provide a novel strategy for development of therapeutic agents to suppress myopia progression. PMID:25018620
21 CFR 886.3320 - Eye sphere implant.
Code of Federal Regulations, 2012 CFR
2012-04-01
... sphere implant is a device intended to be implanted in the eyeball to occupy space following the removal of the contents of the eyeball with the sclera left intact. (b) Classification. Class II. ...
21 CFR 886.3320 - Eye sphere implant.
Code of Federal Regulations, 2013 CFR
2013-04-01
... sphere implant is a device intended to be implanted in the eyeball to occupy space following the removal of the contents of the eyeball with the sclera left intact. (b) Classification. Class II. ...
21 CFR 886.3320 - Eye sphere implant.
Code of Federal Regulations, 2014 CFR
2014-04-01
... sphere implant is a device intended to be implanted in the eyeball to occupy space following the removal of the contents of the eyeball with the sclera left intact. (b) Classification. Class II. ...
NASA Astrophysics Data System (ADS)
Singh, Manmohan; Nair, Achuth; Aglyamov, Salavat R.; Wu, Chen; Han, Zhaolong; Lafon, Ericka; Larin, Kirill V.
2017-02-01
Recent work has shown that the biomechanical properties of tissues in the posterior eye have are critical for understanding the etiology and progression of ocular diseases. For instance, the primary risk for glaucoma is an elevated intraocular pressure (IOP). Weak tissues will deform under the large pressure, causing damage to vital tissues. In addition, scleral elasticity can influence the shape of the eye-globe, altering the axial length. In this work, we utilize a noncontact form of optical coherence elastography (OCE) to quantify the spatial distribution of biomechanical properties of the optic nerve, its surrounding tissues, and posterior sclera on the exterior of in situ porcine eyes in the whole eyeglobe configuration. The OCE measurements were taken at various IOPs to evaluate the biomechanical properties of the tissues as a function of IOP. The air-pulse induced dynamic response of the tissues was linked to Young's modulus by a simple kinematic equation by quantified the damped natural frequency (DNF). The results show that the posterior sclera is not as stiff as the optic nerve and its surrounding tissues ( 460 Hz and 894 Hz at 10 mmHg IOP, respectively). Moreover, the scleral stiffness was generally unaffected by IOP ( 460 Hz at 10 mmHg IOP as compared to 516 Hz at 20 mmHg), whereas the optic nerve and its surrounding tissues stiffened as IOP was increased ( 894 Hz at 10 mmHg to 1221 Hz at 20 mmHg).
Simulation model of an eyeball based on finite element analysis on a supercomputer
Uchio, E.; Ohno, S.; Kudoh, J.; Aoki, K.; Kisielewicz, L. T.
1999-01-01
BACKGROUND/AIMS—A simulation model of the human eye was developed. It was applied to the determination of the physical and mechanical conditions of impacting foreign bodies causing intraocular foreign body (IOFB) injuries. METHODS—Modules of the Hypermesh (Altair Engineering, Tokyo, Japan) were used for solid modelling, geometric construction, and finite element mesh creation based on information obtained from cadaver eyes. The simulations were solved by a supercomputer using the finite element analysis (FEA) program PAM-CRASH (Nihon ESI, Tokyo, Japan). It was assumed that rupture occurs at a strain of 18.0% in the cornea and 6.8% in the sclera and at a stress of 9.4 MPa for both cornea and sclera. Blunt-shaped missiles were shot and set to impact on the surface of the cornea or sclera at velocities of 30 and 60 m/s, respectively. RESULTS—According to the simulation, the sizes of missile above which corneal rupture occurred at velocities of 30 and 60 m/s were 1.95 and 0.82 mm. The missile sizes causing scleral rupture were 0.95 and 0.75 mm at velocities of 30 and 60 m/s. CONCLUSIONS—These results suggest that this FEA model has potential usefulness as a simulation tool for ocular injury and it may provide useful information for developing protective measures against industrial and traffic ocular injuries. PMID:10502567
The eye of the magellanic penguin (Spheniscus magellanicus): structure of the anterior segment.
Suburo, A M; Scolaro, J A
1990-11-01
We undertook a light and scanning electron microscopic study of the eye in the Magellanic penguin (Spheniscus magellanicus). The anatomical peculiarities of the eyeball shape in Sphenisciformes have been previously described by others; here, we show that they are accompanied by several modifications in the organization of the anterior segment of the eye. The main change was found in the portion of opaque sclera extending from the cornea to the anterior border of the scleral ossicles, which was much broader than in other avian eyes. This scleral region was made of a very dense fibrous tissue and was as difficult to cut as the ossicles. The corneo-scleral boundary was also different from that of other birds, since the aqueous humor channel and the pectinate ligament were located 1.0-1.5 mm posterior to the cornea. The osseous ring was formed by 13 bones, including three pairs of over- and underplates. There was a single ciliary muscle, with meridionally oriented striated fibers. They were inserted on a circumference along the boundary between the fibrous sclera and the ossicles, far away from the wall of the aqueous humor channel. On their posterior end, the muscle fibers formed a tendinous structure attached to the inner surface of the sclera and to the outer surface of the ciliary body. Only short zonular fibrils were observed. These anatomical features are probably relevant for the adaptation of penguin eyes to vision on land and in the aquatic environment.
A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis.
Gilger, Brian C; Salmon, Jacklyn H; Wilkie, David A; Cruysberg, Lars P J; Kim, Jonghyeon; Hayat, Matt; Kim, Hyuncheol; Kim, Stephanie; Yuan, Peng; Lee, Susan S; Harrington, Susan M; Murray, Patrick R; Edelhauser, Henry F; Csaky, Karl G; Robinson, Michael R
2006-06-01
To determine the feasibility, safety, and effectiveness of an episcleral or deep scleral lamellar sustained release cyclosporine (CsA) device in a naturally occurring animal model of uveitis. A two-compartment perfusion chamber was used to assess in vitro human and equine scleral permeability of fluorescein, dexamethasone-fluorescein, or CsA. A biodegradable, matrix-reservoir CsA implant was designed, and release rates of CsA were determined in vitro. Tissue CsA levels were measured in eyes with the implant. Horses with equine recurrent uveitis (ERU) received episcleral or deep scleral lamellar CsA implants and were monitored for up to 3 years. Dexamethasone-fluorescein and CsA penetrated the in vitro equine sclera poorly; however, low but detectable levels of CsA were detected intraocularly in vivo. The implant placed episclerally failed to control inflammatory episodes in ERU. CsA implants placed in the deep sclera adjacent to the suprachoroidal space resulted in high levels of CsA in most ocular tissues. In clinical equine patients with ERU, frequency of uveitic flare-ups was significantly decreased after implantation of a deep scleral lamellar CsA implant. Diffusion of CsA across the sclera from the episcleral space was not a feasible method of drug delivery to the equine eye. However, placing a deep scleral lamellar CsA implant adjacent to the suprachoroidal space was effective in achieving therapeutic ocular drug concentrations and controlling uveitis in horses with ERU.
Intraocular distribution of melanin in human, monkey, rabbit, minipig and dog eyes.
Durairaj, Chandrasekar; Chastain, James E; Kompella, Uday B
2012-05-01
The purpose of this study was to quantify the melanin pigment content in sclera, choroid-RPE, and retina, three tissues encountered during transscleral drug delivery to the vitreous, in human, rabbit, monkey, minipig, and dog models. Strain differences were assessed in NZW × NZR F1 and Dutch belted rabbits and Yucatan and Gottingen minipigs. The choroid-RPE and retina tissues were divided into central (posterior pole area) and peripheral (away from posterior pole) regions while the sclera was analyzed without such division. Melanin content in the tissues was analyzed using a colorimetric assay. In all species the rank order for pigment content was: choroid-RPE >retina ≥ sclera, except in humans, where scleral melanin levels were higher than retina and central choroid. The melanin content in a given tissue differed between species. Further, while the peripheral tissue pigment levels tended to be generally higher compared to the central regions, these differences were significant in human in the case of choroid-RPE and in human, monkey, and dogs in the case of retina. Strain difference was observed only in the central choroid-RPE region of rabbits (NZW × NZR F1 >Dutch Belted). Species, strain, and regional differences exist in the melanin pigment content in the tissues of the posterior segment of the eye, with Gottingen minipig being closest to humans among the animals assessed. These differences in melanin content might contribute to differences in drug binding, delivery, and toxicity. Copyright © 2012 Elsevier Ltd. All rights reserved.
Facilitation of transscleral drug delivery by drug loaded magnetic polymeric particles.
Mousavikhamene, Zeynab; Abdekhodaie, Mohammad J; Ahmadieh, Hamid
2017-10-01
A unique method was used to facilitate ocular drug delivery from periocular route by drug loaded magnetic sensitive particles. Injection of particles in periocular space along the eye axis followed by application of magnetic field in front of the eye would trigger the magnetic polymeric particles to move along the direction of magnetic force and reside against the outer surface of the sclera. This technique prevents removal of drug in the periocular space, observed in conventional transscleral drug delivery systems and hence higher amount of drug can enter the eye in a longer period of time. The experiments were performed by fresh human sclera and an experimental setup. Experimental setup was designed by side by side diffusion cell and hydrodynamic and thermal simulation of the posterior segment of the eye were applied. Magnetic polymeric particles were synthesized by alginate as a model polymer, iron oxide nanoparticles as a magnetic agent and diclofenac sodium as a model drug and characterized by SEM, TEM, DLS and FT-IR techniques. According to the SEM images, the size range of particles is around 60 to 800nm. The results revealed that the cumulative drug transfer from magnetic sensitive particles across the sclera improves by 70% in the presence of magnetic field. The results of this research show promising method of drug delivery to use magnetic properties to facilitate drug delivery to the back of the eye. Copyright © 2017. Published by Elsevier B.V.
27-Gauge Vitrectomy for Symptomatic Vitreous Floaters with Topical Anesthesia
Lin, Zhong; Moonasar, Nived; Wu, Rong Han; Seemongal-Dass, Robin R.
2017-01-01
Purpose Traditionally acceptable methods of anesthesia for vitrectomy surgery are quite varied. However, each of these methods has its own potential for complications that can range from minor to severe. The surgery procedure of vitrectomy for symptomatic vitreous floaters is much simpler, mainly reflecting in the nonuse of sclera indentation, photocoagulation, and the apparently short surgery duration. The use of 27-gauge cannulae makes the puncture of the sclera minimally invasive. Hence, retrobulbar anesthesia, due to its rare but severe complications, seemed excessive for this kind of surgery. Method Three cases of 27-gauge, sutureless pars plana vitrectomy for symptomatic vitreous floaters with topical anesthesia are reported. Results The vitrectomy surgeries were successfully performed with topical anesthesia (proparacaine, 0.5%) without operative or postoperative complications. Furthermore, none of the patients experienced apparent pain during or after the surgery. Conclusion Topical anesthesia can be considered for 27-guage vitrectomy in patients with symptomatic vitreous floaters. PMID:28203195
27-Gauge Vitrectomy for Symptomatic Vitreous Floaters with Topical Anesthesia.
Lin, Zhong; Moonasar, Nived; Wu, Rong Han; Seemongal-Dass, Robin R
2017-01-01
Traditionally acceptable methods of anesthesia for vitrectomy surgery are quite varied. However, each of these methods has its own potential for complications that can range from minor to severe. The surgery procedure of vitrectomy for symptomatic vitreous floaters is much simpler, mainly reflecting in the nonuse of sclera indentation, photocoagulation, and the apparently short surgery duration. The use of 27-gauge cannulae makes the puncture of the sclera minimally invasive. Hence, retrobulbar anesthesia, due to its rare but severe complications, seemed excessive for this kind of surgery. Three cases of 27-gauge, sutureless pars plana vitrectomy for symptomatic vitreous floaters with topical anesthesia are reported. The vitrectomy surgeries were successfully performed with topical anesthesia (proparacaine, 0.5%) without operative or postoperative complications. Furthermore, none of the patients experienced apparent pain during or after the surgery. Topical anesthesia can be considered for 27-guage vitrectomy in patients with symptomatic vitreous floaters.
Chen, Qiuhong; Zheng, Yu; Li, Ye; Zeng, Ying; Kuang, Jianchao; Hou, Shixiang; Li, Xiaohui
2012-05-01
The aim of the present work was to evaluate the effect of deacetylated gellan gum on delivering hydrophilic drug to the posterior segment of the eye. An aesculin-containing in situ gel based on deacetylated gellan gum (AG) was prepared and characterized. In vitro corneal permeation across isolated rabbit cornea of aesculin between AG and aesculin solution (AS) was compared. The results showed that deacetylated gellan gum promotes corneal penetration of aesculin. Pharmacokinetics and ocular tissue distribution of aesculin after topical administration in rabbit eye showed that AG greatly improved aesculin accumulation in posterior segmentsrelative to AS, which was probably attributed to conjunctivital/sclera pathway. The area-under-the-curve (AUC) for AG in aqueous humor, choroid-retina, sclera and iris-ciliary body were significantly larger than those of AS. AG can be used as a potential carrier for broading the application of aesculin.
NASA Astrophysics Data System (ADS)
Poddar, Raju; Zawadzki, Robert J.; Cortés, Dennis E.; Mannis, Mark J.; Werner, John S.
2015-06-01
We present in vivo volumetric depth-resolved vasculature images of the anterior segment of the human eye acquired with phase-variance based motion contrast using a high-speed (100 kHz, 105 A-scans/s) swept source optical coherence tomography system (SSOCT). High phase stability SSOCT imaging was achieved by using a computationally efficient phase stabilization approach. The human corneo-scleral junction and sclera were imaged with swept source phase-variance optical coherence angiography and compared with slit lamp images from the same eyes of normal subjects. Different features of the rich vascular system in the conjunctiva and episclera were visualized and described. This system can be used as a potential tool for ophthalmological research to determine changes in the outflow system, which may be helpful for identification of abnormalities that lead to glaucoma.
New developments in ophthalmic applications of ultrafast lasers
NASA Astrophysics Data System (ADS)
Spooner, Greg J. R.; Juhasz, Tibor; Ratkay-Traub, Imola; Djotyan, Gagik P.; Horvath, Christopher; Sacks, Zachary S.; Marre, Gabrielle; Miller, Doug L.; Williams, A. R.; Kurtz, Ron M.
2000-05-01
The eye is potentially an ideal target for high precision surgical procedures utilizing ultrafast lasers. We present progress on corneal applications now being tested in humans and proof of concept ex vivo demonstrations of new applications in the sclera and lens. Two corneal refractive procedures were tested in partially sighted human eyes: creation of corneal flaps prior to excimer ablation (Femto- LASIK) and creation of corneal channels and entry cuts for placement of intracorneal ring segments (Femto-ICRS). For both procedures, results were comparable to standard treatments, with the potential for improved safety, accuracy and reproducibility. For scleral applications, we evaluated the potential of femtosecond laser glaucoma surgery by demonstrating resections in ex vivo human sclera using dehydrating agents to induce tissue transparency. For lens applications, we demonstrate in an ex vivo model the use of photodisruptively-nucleated ultrasonic cavitation for local and non-invasive tissue interaction.
Iris recognition: on the segmentation of degraded images acquired in the visible wavelength.
Proença, Hugo
2010-08-01
Iris recognition imaging constraints are receiving increasing attention. There are several proposals to develop systems that operate in the visible wavelength and in less constrained environments. These imaging conditions engender acquired noisy artifacts that lead to severely degraded images, making iris segmentation a major issue. Having observed that existing iris segmentation methods tend to fail in these challenging conditions, we present a segmentation method that can handle degraded images acquired in less constrained conditions. We offer the following contributions: 1) to consider the sclera the most easily distinguishable part of the eye in degraded images, 2) to propose a new type of feature that measures the proportion of sclera in each direction and is fundamental in segmenting the iris, and 3) to run the entire procedure in deterministically linear time in respect to the size of the image, making the procedure suitable for real-time applications.
Serratia marcescens endophthalmitis after pterygium surgery: a case report.
Yi, Myeong Yeon; Chung, Jin Kwon; Choi, Kyung Seek
2017-11-02
To report a case of Serratia marcescens endophthalmitis after pterygium surgery using the bare sclera technique with mitomycin C (MMC). A 69-year-old male patient underwent pterygium excision surgery using the bare sclera technique and 0.02% MMC. The patient presented with decreased visual acuity and pain from the day after the operation. Trans pars plana vitrectomy was performed and intravitreal antibiotics were administered. Cultures from the aqueous humor and intraocular lens were all positive for S. marcescens, which was sensitive to an empiric antibiotic regimen. The best corrected distant visual acuity, 1 month after treatment, was a finger count/50 cm, but the retinal layer structure and the vasculature were relatively well preserved. This is the first reported case of S. marcescens endophthalmitis after pterygium surgery. Endophthalmitis caused by S. marcescens has a devastating visual prognosis and may show a high clinical risk-benefit ratio for the application of MMC in pterygium surgery.
Evaluation of human sclera after femtosecond laser ablation using two photon and confocal microscopy
NASA Astrophysics Data System (ADS)
Sun, Hui; Kurtz, Ronald; Juhasz, Tibor
2012-08-01
Glaucoma is the second-leading cause of blindness worldwide and is often associated with elevated intraocular pressure (IOP). Partial thickness intrascleral channels can be created with a femtosecond laser operating at a wavelength of 1700 nm. Such channels have the potential to increase outflow facility and reduce elevated IOP. Analysis of the dimensions and location of these channels is important in understanding their effects. We describe the application of two-photon microscopy and confocal microscopy for noninvasive imaging of the femtosecond laser created partial-thickness scleral channels in human cadaver eyes. High-resolution images, hundreds of microns deep in the sclera, were obtained to allow determination of the shape and dimension of such channels. This demonstrates that concept of integrating femtosecond laser surgery, and two-photon and confocal imaging has the future potential for image-guided high-precision surgery in transparent and translucent tissue.
Evaluation of tissue interactions with mechanical elements of a transscleral drug delivery device.
Cohen, Sarah J; Chan, Robison V Paul; Keegan, Mark; Andreoli, Christopher M; Borenstein, Jeffrey T; Miller, Joan W; Gragoudas, Evangelos S
2012-03-12
The goal of this work was to evaluate tissue-device interactions due to implantation of a mechanically operated drug delivery system onto the posterior sclera. Two test devices were designed and fabricated to model elements of the drug delivery device-one containing a free-spinning ball bearing and the other encasing two articulating gears. Openings in the base of test devices modeled ports for drug passage from device to sclera. Porous poly(tetrafluoroethylene) (PTFE) membranes were attached to half of the gear devices to minimize tissue ingrowth through these ports. Test devices were sutured onto rabbit eyes for 10 weeks. Tissue-device interactions were evaluated histologically and mechanically after removal to determine effects on device function and changes in surrounding tissue. Test devices were generally well-tolerated during residence in the animal. All devices encouraged fibrous tissue formation between the sclera and the device, fibrous tissue encapsulation and invasion around the device, and inflammation of the conjunctiva. Gear devices encouraged significantly greater inflammation in all cases and a larger rate of tissue ingrowth. PTFE membranes prevented tissue invasion through the covered drug ports, though tissue migrated in through other smaller openings. The torque required to turn the mechanical elements increased over 1000 times for gear devices, but only on the order of 100 times for membrane-covered gear devices and less than 100 times for ball bearing devices. Maintaining a lower device profile, minimizing microscale motion on the eye surface and covering drug ports with a porous membrane may minimize inflammation, decreasing the risk of damage to surrounding tissues and minimizing disruption of device operation.
Cerebrospinal Fluid Pressure: Revisiting Factors Influencing Optic Nerve Head Biomechanics
Hua, Yi; Voorhees, Andrew P.; Sigal, Ian A.
2018-01-01
Purpose To model the sensitivity of the optic nerve head (ONH) biomechanical environment to acute variations in IOP, cerebrospinal fluid pressure (CSFP), and central retinal artery blood pressure (BP). Methods We extended a previously published numerical model of the ONH to include 24 factors representing tissue anatomy and mechanical properties, all three pressures, and constraints on the optic nerve (CON). A total of 8340 models were studied to predict factor influences on 98 responses in a two-step process: a fractional factorial screening analysis to identify the 16 most influential factors, followed by a response surface methodology to predict factor effects in detail. Results The six most influential factors were, in order: IOP, CON, moduli of the sclera, lamina cribrosa (LC) and dura, and CSFP. IOP and CSFP affected different aspects of ONH biomechanics. The strongest influence of CSFP, more than twice that of IOP, was on the rotation of the peripapillary sclera. CSFP had similar influence on LC stretch and compression to moduli of sclera and LC. On some ONHs, CSFP caused large retrolamina deformations and subarachnoid expansion. CON had a strong influence on LC displacement. BP overall influence was 633 times smaller than that of IOP. Conclusions Models predict that IOP and CSFP are the top and sixth most influential factors on ONH biomechanics. Different IOP and CSFP effects suggest that translaminar pressure difference may not be a good parameter to predict biomechanics-related glaucomatous neuropathy. CON may drastically affect the responses relating to gross ONH geometry and should be determined experimentally. PMID:29332130
Brizola, Evelise; Zambrano, Marina Bauer; Pinheiro, Bruna de Souza; Vanz, Ana Paula; Félix, Têmis Maria
2017-01-01
To characterize the fracture pattern and the clinical history at the time of diagnosis of osteogenesis imperfecta. In this retrospective study, all patients with osteogenesis imperfecta, of both genders, aged 0-18 years, who were treated between 2002 and 2014 were included. Medical records were assessed to collect clinical data, including the presence of blue sclerae, dentinogenesis imperfecta, positive familial history of osteogenesis imperfecta, and the site of the fractures. In addition, radiographic findings at the time of the diagnosis were reviewed. Seventy-six patients (42 females) were included in the study. Individuals' age ranged from 0 to 114 months, with a median (interquartile range) age of 38 (6-96) months. Blue sclerae were present in 93.4% of patients, dentinogenesis imperfecta was observed in 27.6% of patients, and wormian bones in 29.4% of them. The number of fractures at diagnosis ranged from 0 to 17, with a median of 3 (2-8) fractures. Forty (57%) patients had fractures of the upper and lower extremities, and 9 patients also had spinal fractures. The diagnosis was performed at birth in 85.7% of patients with type 3, and 39.3% of those with type 4/5 of the disorder. Osteogenesis imperfecta is a genetic disorder with distinctive clinical features such as bone fragility, recurrent fractures, blue sclerae, and dentinogenesis imperfecta. It is important to know how to identify these characteristics in order to facilitate the diagnosis, optimize the treatment, and differentiate osteogenesis imperfecta from other disorders that also can lead to fractures.
Brizola, Evelise; Zambrano, Marina Bauer; Pinheiro, Bruna de Souza; Vanz, Ana Paula; Félix, Têmis Maria
2017-01-01
ABSTRACT Objective: To characterize the fracture pattern and the clinical history at the time of diagnosis of osteogenesis imperfecta. Methods: In this retrospective study, all patients with osteogenesis imperfecta, of both genders, aged 0-18 years, who were treated between 2002 and 2014 were included. Medical records were assessed to collect clinical data, including the presence of blue sclerae, dentinogenesis imperfecta, positive familial history of osteogenesis imperfecta, and the site of the fractures. In addition, radiographic findings at the time of the diagnosis were reviewed. Results: Seventy-six patients (42 females) were included in the study. Individuals’ age ranged from 0 to 114 months, with a median (interquartile range) age of 38 (6-96) months. Blue sclerae were present in 93.4% of patients, dentinogenesis imperfecta was observed in 27.6% of patients, and wormian bones in 29.4% of them. The number of fractures at diagnosis ranged from 0 to 17, with a median of 3 (2-8) fractures. Forty (57%) patients had fractures of the upper and lower extremities, and 9 patients also had spinal fractures. The diagnosis was performed at birth in 85.7% of patients with type 3, and 39.3% of those with type 4/5 of the disorder. Conclusions: Osteogenesis imperfecta is a genetic disorder with distinctive clinical features such as bone fragility, recurrent fractures, blue sclerae, and dentinogenesis imperfecta. It is important to know how to identify these characteristics in order to facilitate the diagnosis, optimize the treatment, and differentiate osteogenesis imperfecta from other disorders that also can lead to fractures. PMID:28977334
Ghoneim, Ehab M.; Abd-El Ghny, Ahmed A.; Gab-Allah, Amro A.; Kamal, Mohamed Z.
2011-01-01
Purpose: To compare the efficacy of preoperative local injection of mitomycin C (MMC) to intraoperative application of MMC in the prevention of pterygium recurrence after surgical removal. Materials and Methods: Seventy eyes of 70 patients with primary pterygia were randomly allocated to two groups. The first group (Group A, 35 eyes) received 0.1 ml of 0.15 mg/ml of subconjunctival MMC injected into the head of the pterygium 24 h before surgical excision with the bare sclera technique. The second group (Group B 35 eyes) underwent surgical removal with the bare sclera technique with intraoperative application of MMC (0.15 mg/ml) over bare sclera for 3 min. The study was performed between March 2007 and December 2008, and follow up was performed for 1 year postoperatively. Differences between frequencies in both groups were compared by the Chi-square test or Fisher exact test. Differences between means in both groups were compared by Student’s t-test. P < 0.05 was considered significant. Results: The rate of pterygium recurrence was 5.70% in Group A and 8.57% in Group B at 1 year postoperatively (P>0.05). Postoperatively, scleral thinning occurred in one eye in each group that resolved by 5 months postoperatively. No serious postoperative complications occurred in either group. Conclusion: Preoperative local injection of 0.15 mg/ml MMC is as effective as intraoperative topical application of 0.15 mg/ml MMC for preventing pterygium recurrence after surgical removal. PMID:21572732
Yeh, Lung-Kun; Liu, Chia-Yang; Kao, Winston W.-Y.; Huang, Chang-Jen; Hu, Fung-Rong; Chien, Chung-Liang; Wang, I-Jong
2010-01-01
The lumican gene (lum), which encodes one of the major keratan sulfate proteoglycans (KSPGs) in the vertebrate cornea and sclera, has been linked to axial myopia in humans. In this study, we chose zebrafish (Danio rerio) as an animal model to elucidate the role of lumican in the development of axial myopia. The zebrafish lumican gene (zlum) spans ∼4.6 kb of the zebrafish genome. Like human (hLUM) and mouse (mlum), zlum consists of three exons, two introns, and a TATA box-less promoter at the 5′-flanking region of the transcription initiation site. Sequence analysis of the cDNA predicts that zLum encodes 344 amino acids. zLum shares 51% amino acid sequence identity with human lumican. Similar to hLUM and mlum, zlum mRNA is expressed in the eye and many other tissues, such as brain, muscle, and liver as well. Transgenic zebrafish harboring an enhanced GFP reporter gene construct downstream of a 1.7-kb zlum 5′-flanking region displayed enhanced GFP expression in the cornea and sclera, as well as throughout the body. Down-regulation of zlum expression by antisense zlum morpholinos manifested ocular enlargement resembling axial myopia due to disruption of the collagen fibril arrangement in the sclera and resulted in scleral thinning. Administration of muscarinic receptor antagonists, e.g. atropine and pirenzepine, effectively subdued the ocular enlargement caused by morpholinos in in vivo zebrafish larvae assays. The observation suggests that zebrafish can be used as an in vivo model for screening compounds in treating myopia. PMID:20551313
Cruz-Perez, Benjamin; Tang, Junhua; Morris, Hugh J.; Palko, Joel R.; Pan, Xueliang; Hart, Richard T.; Liu, Jun
2014-01-01
This study aimed to characterize the mechanical responses of the sclera, the white outer coat of the eye, under equal-biaxial loading with unrestricted shear. An ultrasound speckle tracking technique was used to measure tissue deformation through sample thickness, expanding the capabilities of surface strain techniques. Eight porcine scleral samples were tested within 72 hours postmortem. High resolution ultrasound scans of scleral cross-sections along the two loading axes were acquired at 25 consecutive biaxial load levels. An additional repeat of the biaxial loading cycle was performed to measure a third normal strain emulating a strain gauge rosette for calculating the in-plane shear. The repeatability of the strain measurements during identical biaxial ramps was evaluated. A correlation-based ultrasound speckle tracking algorithm was used to compute the displacement field and determine the distributive strains in the sample cross-sections. A Fung type constitutive model including a shear term was used to determine the material constants of each individual specimen by fitting the model parameters to the experimental stress-strain data. A non-linear stress-strain response was observed in all samples. The meridian direction had significantly larger strains than the circumferential direction during equal-biaxial loadings (P’s<0.05). The stiffness along the two directions were also significantly different (P=0.02) but highly correlated (R2=0.8). These results showed that the mechanical properties of the porcine sclera were nonlinear and anisotropic under biaxial loading. This work has also demonstrated the feasibility of using ultrasound speckle tracking for strain measurements during mechanical testing. PMID:24438767
Genetics Home Reference: congenital plasminogen deficiency
... inside of the eyelids. However, in about one-third of cases, ligneous conjunctivitis over the sclera grows onto the cornea, which is the clear covering that protects the colored part of the eye (the iris) and pupil. Such growths can tear ...
Duan, Yi-Qin; Yang, Ye-Zhen; Huang, Xue-Tao; Lin, Ding
2017-11-01
To compare the demethylvancomycin's diffusion-deposition characteristics in the ocular solid tissues of sustained subtenon drug delivery with subconjunctival injection. Sixty adult white rabbits were randomly assigned to the subtenon drug delivery group and the subconjunctival injection group. The subtenon drug delivery group was continuously infused demethylvancomycin to the subtenon of rabbits. The subconjunctival injection group was injected demethylvancomycin to the subconjunctival of rabbits. Cornea, iris and sclera were collected for high-performance liquid chromatography analyses to determine drug concentrations at one hour, three hours, six hours, 12 h and 24 h of drug administration. WinNonlin 6.3 was used to calculate the parameters of cumulative area under the curve (AUC cum ) of demethylvancomycin. The peak levels of demethylvancomycin concentration of the subtenon drug delivery group and the subconjunctival injection group were 92.406 ± 21.555 and 51.778 ± 14.001 μg/g in cornea, 28.451 ± 10.229 μg/g and 42.271 ± 27.291 μg/g in iris, 153.166 ± 51.738 μg/g and 57.423 ± 18.480 μg/g in sclera. The differences of concentrations between the two groups in cornea and sclera were statistically significant (F = 487.775, p < 0.001; F = 132.748, p < 0.001). The difference in iris was not statistically significant (F = 4.848, p = 0.064). The maximum of AUC cum of the subtenon drug delivery group and the subconjunctival injection group was 1808.23 h * μg/g and 273.73 h * μg/g in cornea, 489.12 h * μg/g and 216.16 h * μg/g in iris and 2166.34 h * μg/g and 392.57 h * μg/g in sclera at 24 h of drug administration. The sustained subtenon drug delivery had a better drug permeability and accumulation in the intraocular solid tissue compared to subconjunctival injection, which demonstrated it was probably a promising and effective approach for treating posterior segment diseases and endophthalmitis.
Optic nerve head and intraocular pressure in the guinea pig eye.
Ostrin, Lisa A; Wildsoet, Christine F
2016-05-01
The guinea pig is becoming an increasingly popular model for studying human myopia, which carries an increased risk of glaucoma. As a step towards understanding this association, this study sought to characterize the normal, developmental intraocular pressure (IOP) profiles, as well as the anatomy of the optic nerve head (ONH) and adjacent sclera of young guinea pigs. IOP was tracked in pigmented guinea pigs up to 3 months of age. One guinea pig was imaged in vivo with OCT and one with a fundus camera. The eyes of pigmented and albino guinea pigs (ages 2 months) were enucleated and sections from the posterior segment, including the ONH and surrounding sclera, processed for histological analyses - either hematoxylin and eosin (H&E) staining of paraffin embedded, sectioned tissue (n = 1), or cryostat sectioned tissue, processed for immunohistochemistry (n = 3), using primary antibodies against collagen types I-V, elastin, fibronectin and glial fibrillary acidic protein (GFAP). Transmission and scanning electron microscopy (TEM, SEM) studies of ONHs were also undertaken (n = 2 & 5 respectively). Mean IOPs ranged from 17.33 to 22.7 mmHg, increasing slightly across the age range studied, and the IOPs of individual animals also exhibited diurnal variations, peaking in the early morning (mean of 25.8, mmHg, ∼9 am), and decreasing across the day. H&E-stained sections showed retinal ganglion cell axons organized into fascicles in the prelaminar and laminar region of the ONHs, with immunostained sections revealing collagen types I, III, IV and V, as well as elastin, GFAP and fibronectin in the ONHs. SEM revealed a well-defined lamina cribrosa (LC), with radially-oriented collagen beams. TEM revealed collagen fibrils surrounding non-myelinated nerve fiber bundles in the LC region, with myelination and decreased collagen posterior to the LC. The adjacent sclera comprised mainly crimped collagen fibers in a crisscross arrangement. Both the sclera and LC were qualitatively similar in structure in pigmented and albino guinea pigs. The well-organized, collagen-based LC of the guinea pig ONH is similar to that described for tree shrews and more similar to the human LC than that of other rodents that lack collagen. Based on these latter structural similarities the guinea pig would seem a promising model for investigating the relationship between myopia and glaucoma. Copyright © 2015 Elsevier Ltd. All rights reserved.
Scar remodeling after strabismus surgery.
Ludwig, I H
1999-01-01
PURPOSE: Patients with overcorrected strabismus (and several patients with undercorrection after extraocular muscle resection) underwent exploration of previously operated muscles, with the intention of advancing their tendons to prevent the need for surgery on additional muscles. Unexpectedly, it was found that, in many cases, an elongated scar segment of variable length was interposed between the muscle and its insertion site on the sclera. Laboratory investigations were carried out to elucidate the underlying mechanism(s) and to create an animal model of the disorder. METHODS: Lengthened scars were repaired on 198 muscles during 134 procedures performed on 123 patients. The scars consisted of amorphous connective tissue interposed between the globe and normal tendon. Repair was accomplished by excision of the scar and reattachment of the muscle to sclera, using absorbable sutures in 64 cases and nonabsorbable sutures in 70 cases. Histopathologic examination was performed on 82 clinical specimens, and tissue culture studies were performed on 7 specimens. To develop an animal model, 10 New Zealand white rabbits underwent bilateral superior rectus resection. Half of the eyes received sub-Tenon's injections of collagenase over the operative site during weeks 2, 3, 5, and 6 postoperatively; the other half received saline solution injections on the same schedule. At 10 weeks, half the sites were studied histologically, and the other half underwent collagen creep analysis. In a second study, the use of absorbable versus nonabsorbable sutures was compared in the rabbit model. RESULTS: In the clinical cases, the mean length of the elongated scar segments was 4.2 mm. A total of 105 of the 134 repair procedures were judged successful. Thirty-one procedures resulted in recurrence of the original overcorrection; 7 of these had documented restretches. Factors that distinguished patients with stretched scars from patients with classic slipped muscles included minimal or no limitation of versions, less separation of the tendons from sclera, and thicker appearance of the scar segments. The use of nonabsorbable sutures in the repair procedure reduced the recurrence rate. Histologic examination of the clinical stretched scar specimens showed dense connective tissue that was less well organized compared with normal tendon. In the tissue culture studies, cells cultured from the stretched scar specimens grew rapidly and were irregularly shaped. A high-molecular-weight protein was identified in the culture medium. By contrast, cells cultured from normal tendon (controls) grew more slowly and regularly, stopped growing at 4 days, and produced less total protein than cultured stretched scar specimens. In the animal model studies, the collagenase-treated sites showed elongated scars with increased collagen between the muscle and the sclera, as well as increased collagen creep rates, compared with the saline-treated controls. The use of nonabsorbable sutures in collagenase-treated animal model surgery sites was associated with shorter, thicker scars compared with similar sites sutured with absorbable sutures. CONCLUSIONS: A lengthened or stretched, remodeled scar between an operated muscle tendon and sclera is a common occurrence and is a factor contributing to the variability of outcome after strabismus repair, even years later. This abnormality may be revealed by careful exploration of previously operated muscles. Definitive repair requires firm reattachment of tendon to sclera with nonabsorbable suture support. Images FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 10 FIGURE 11 FIGURE 12 FIGURE 13 FIGURE 14 FIGURE 15 FIGURE 16 FIGURE 17 FIGURE 18 FIGURE 19 FIGURE 20 FIGURE 21 FIGURE 22 FIGURE 23 FIGURE 24 FIGURE 25 FIGURE 26 FIGURE 27 FIGURE 28 FIGURE 29 FIGURE 30 FIGURE 31 FIGURE 32 FIGURE 33 FIGURE 34 FIGURE 35 FIGURE 36 FIGURE 37 FIGURE 38 FIGURE 39 FIGURE 40 FIGURE 41 FIGURE 42 FIGURE 43 FIGURE 44 FIGURE 45 FIGURE 46 FIGURE 52 FIGURE 53 FIGURE 54 FIGURE 55 FIGURE 58 FIGURE 59 FIGURE 60 FIGURE 61 FIGURE 62 FIGURE 63 FIGURE 64 PMID:10703142
OCT-based profiler for automating ocular surface prosthetic fitting (Conference Presentation)
NASA Astrophysics Data System (ADS)
Mujat, Mircea; Patel, Ankit H.; Maguluri, Gopi N.; Iftimia, Nicusor V.; Patel, Chirag; Agranat, Josh; Tomashevskaya, Olga; Bonte, Eugene; Ferguson, R. Daniel
2016-03-01
The use of a Prosthetic Replacement of the Ocular Surface Environment (PROSE) device is a revolutionary treatment for military patients that have lost their eyelids due to 3rd degree facial burns and for civilians who suffer from a host of corneal diseases. However, custom manual fitting is often a protracted painful, inexact process that requires multiple fitting sessions. Training for new practitioners is a long process. Automated methods to measure the complete corneal and scleral topology would provide a valuable tool for both clinicians and PROSE device manufacturers and would help streamline the fitting process. PSI has developed an ocular anterior-segment profiler based on Optical Coherence Tomography (OCT), which provides a 3D measure of the surface of the sclera and cornea. This device will provide topography data that will be used to expedite and improve the fabrication process for PROSE devices. OCT has been used to image portions of the cornea and sclera and to measure surface topology for smaller contact lenses [1-3]. However, current state-of-the-art anterior eye OCT systems can only scan about 16 mm of the eye's anterior surface, which is not sufficient for covering the sclera around the cornea. In addition, there is no systematic method for scanning and aligning/stitching the full scleral/corneal surface and commercial segmentation software is not optimized for the PROSE application. Although preliminary, our results demonstrate the capability of PSI's approach to generate accurate surface plots over relatively large areas of the eye, which is not currently possible with any other existing platform. Testing the technology on human volunteers is currently underway at Boston Foundation for Sight.
Material Properties of the Posterior Human Sclera☆
Grytz, Rafael; Fazio, Massimo A.; Girard, Michael J.A.; Libertiaux, Vincent; Bruno, Luigi; Gardiner, Stuart; Girkin, Christopher A.; Downs, J. Crawford
2013-01-01
To characterize the material properties of posterior and peripapillary sclera from human donors, and to investigate the macro- and micro-scale strains as potential control mechanisms governing mechanical homeostasis. Posterior scleral shells from 9 human donors aged 57–90 years were subjected to IOP elevations from 5 to 45 mmHg and the resulting full-field displacements were recorded using laser speckle interferometry. Eye-specific finite element models were generated based on experimentally measured scleral shell surface geometry and thickness. Inverse numerical analyses were performed to identify material parameters for each eye by matching experimental deformation measurements to model predictions using a microstructure-based constitutive formulation that incorporates the crimp response and anisotropic architecture of scleral collagen fibrils. The material property fitting produced models that fit both the overall and local deformation responses of posterior scleral shells very well. The nonlinear stiffening of the sclera with increasing IOP was well reproduced by the uncrimping of scleral collagen fibrils, and a circumferentially-aligned ring of collagen fibrils around the scleral canal was predicted in all eyes. Macroscopic in-plane strains were significantly higher in peripapillary region then in the mid-periphery. In contrast, the meso- and micro-scale strains at the collagen network and collagen fibril level were not significantly different between regions. The elastic response of the posterior human sclera can be characterized by the anisotropic architecture and crimp response of scleral collagen fibrils. The similar collagen fibril strains in the peripapillary and mid-peripheral regions support the notion that the scleral collagen architecture including the circumpapillary ring of collagen fibrils evolved to establish optimal load bearing conditions at the collagen fibril level. PMID:23684352
Liu, Hsin-Hua; Kenning, Megan S; Jobling, Andrew I; McBrien, Neville A; Gentle, Alex
2017-04-01
The purpose of this study was to determine the endogenous regulation pattern of tissue inhibitor of metalloproteinase-2 (TIMP-2) in the tree shrew sclera during myopia development and investigate the capacity of exogenous TIMP-2 to inhibit matrix metalloproteinase-2 (MMP-2) in vitro and both scleral collagen degradation and myopia development in vivo. TIMP-2 expression in the sclera during myopia development was assessed using polymerase chain reaction. In vitro TIMP-2 inhibition of MMP-2 was investigated using a gelatinase activity plate assay and zymography. Tree shrews were injected with a collagen precursor before undergoing monocular form deprivation and concurrent daily subconjunctival injections of either TIMP-2 or vehicle to the form-deprived eye. In vivo ocular biometry changes were monitored, and scleral tissue was collected after 12 days and assayed for collagen degradation. The development of myopia was associated with a mean reduction in TIMP-2 mRNA expression after 5 days of form deprivation (P < 0.01). Both activation and activity of MMP-2 were inhibited by TIMP-2 with an IC50 of 10 to 20 and 2 nM, respectively. In vivo exogenous addition of TIMP-2 significantly reduced myopia development (P < 0.01), due to reduced vitreous chamber elongation (P < 0.01). In vivo TIMP-2 treatment also significantly inhibited posterior scleral collagen degradation relative to vehicle-treated eyes (P < 0.01), with levels similar to those in control eyes. Myopia development in mammals is associated with reduced expression of TIMP-2, which contributes to increased degradative activity in the sclera. It follows that replenishment of this TIMP-2 significantly reduced the rate of both scleral collagen degradation and myopia development.
Heterologous, Fresh, Human Donor Sclera as Patch Graft Material in Glaucoma Drainage Device Surgery.
Tsoukanas, Dimitrios; Xanthopoulou, Paraskevi; Charonis, Alexandros C; Theodossiadis, Panagiotis; Kopsinis, Gerasimos; Filippopoulos, Theodoros
2016-07-01
To determine the safety and efficacy of fresh, human sclera allografts as a patch graft material in glaucoma drainage device (GDD) surgery. Retrospective, noncomparative, interventional, consecutive case series. All GDD cases operated between 2008 and 2013 in which fresh human corneoscleral rims were used immediately after the central corneal button was used for penetrating or endothelial keratoplasty. Surgery was performed by 2 surgeons at 2 facilities. The Ahmed Glaucoma Valve (FP-7) was used exclusively in this cohort. Sixty-four eyes of 60 patients were identified; demographic data were recorded along with intraocular pressure (IOP), medication requirements, visual acuity, complications, and subsequent interventions. Incidence of complications. IOP and medication requirements at the last follow-up. Quilified success utilizing Tube Versus Trabeculectomy study criteria. The mean age of the cohort was 66.2±19.1 years; the average preoperative IOP was 33.2±11.1 mm Hg on 4.2±1.3 IOP-lowering agents before GDD surgery. IOP decreased significantly to 14.1±4.7 mm Hg (P<0.001) on 1.6±1.2 IOP-lowering agents (P<0.001) after an average follow-up of 18.2±15.4 months. There were no cases of early or late blebitis or endophthalmitis, and there was 1 case of conjunctival erosion and tube/plate exposure (1.6%) occurring 30 days after surgery. Qualified success was estimated as 90.5% and 81% at 1 and 2 years, respectively, using Tube Versus Trabeculectomy study criteria. Heterologous, fresh, human donor sclera appears to be a safe material for GDD tube coverage. It provides a cost-efficient alternative compared with traditional patch graft materials associated with a low risk of pathogen transmission.
Clark, Simon J.; Keenan, Tiarnan D. L.; Fielder, Helen L.; Collinson, Lisa J.; Holley, Rebecca J.; Merry, Catherine L. R.; van Kuppevelt, Toin H.; Day, Anthony J.; Bishop, Paul N.
2011-01-01
Purpose. To map the distribution of different classes of glycosaminoglycans (GAGs) in the healthy human retina, choroid, and sclera. Methods. Frozen tissue sections were made from adult human donor eyes. The GAG chains of proteoglycans (PGs) were detected with antibodies directed against various GAG structures (either directly or after pretreatment with GAG-degrading enzymes); hyaluronan (HA) was detected using biotinylated recombinant G1-domain of human versican. The primary detection reagents were identified with FITC-labeled probes and analyzed by fluorescence microscopy. Results. Heparan sulfate (HS), chondroitin sulfate (CS), dermatan sulfate (DS), and HA were present throughout the retina and choroid, but keratan sulfate (KS) was detected only in the sclera. HS labeling was particularly strong in basement membrane–containing structures, the nerve fiber layer (NFL), and retinal pigment epithelium (RPE)—for example, intense staining was seen with an antibody that binds strongly to sequences containing 3-O-sulfation in the internal limiting membrane (ILM) and in the basement membrane of blood vessels. Unsulfated CS was seen throughout the retina, particularly in the ILM and interphotoreceptor matrix (IPM) with 6-O-sulfated CS also prominent in the IPM. There was labeling for DS throughout the retina and choroid, especially in the NFL, ganglion cell layer, and blood vessels. Conclusions. The detection of GAG chains with specific probes and fluorescence microscopy provides for the first time a detailed analysis of their compartmentalization in the human retina, by both GAG chain type and sulfation pattern. This reference map provides a basis for understanding the functional regulation of GAG-binding proteins in health and disease processes. PMID:21746802
Schaeffel, F
2011-09-01
This review summarises some recent aspects of myopia research. The following conclusions have been drawn. As long as myopia progression is visually controlled, at least three different interventions are possible: (i) spectacles/contact lenses which correct only the centre of the visual field and leave the periphery somewhat myopic, (ii) outdoor activity or equivalent temporary increase in illuminance, (iii) pharmacological intervention of retinal growth signals that are transmitted to the underlying sclera. Options (i) and (ii) can be used without risks although there is still room for improvement of the variables. Option (iii) has re-entered a new phase of orientation with new searches for candidate targets after previous testing with muskarinic antagonists (pirenzepine) in children did not enter phase 3 level. If myopia is outside the range over which it is visually controlled by emmetropisation (in the case of high and pathological myopias), in principle the possibility exists to improve the mechanical stability of the sclera pharmacologically. However, there is still a need for more research. Up to now, the mechanical weakness of the sclera in highly mopyic eyes is surgically stabilised by "scleral buckling". However, these procedures have found limited acceptance since the effects were not very reliable. In 40 - 50 % of the cases of high myopia, degenerative processes are found in the retina which can be seen as consequence of the mechanical tension in the fundus, but may also be indepedent of this factor (no significant correlation with axial length!). In part they can be slowed down by intravitreal anti-VEGF therapy. A long-term study from Denmark has shown that most patients with myopia of between 6-9 dpt during puberty reach retirement age without disabling visual loss. © Georg Thieme Verlag KG Stuttgart · New York.
Kałużny, Jakub J; Grzanka, Dariusz; Wiśniewska, Halina; Niewińska, Alicja; Kałużny, Bartłomiej J; Grzanka, Alina
2012-10-01
The purpose of the study is an analysis of intrascleral drainage vessels formed in rabbits' eyes after non-penetrating deep sclerectomy (NPDS) with absorbable and non-absorbable implants, and comparison to eyes in which surgery was performed without implanted material. NPDS was carried out in 12 rabbits, with implantation of non-absorbable methacrylic hydrogel (N=10 eyes) or absorbable cross-linked sodium hyaluronate (N=6 eyes), or without any implant (N=8 eyes). All the animals were euthanized 1 year after surgery. Twenty-one eyeballs were prepared for light microscopy and 3 were prepared for transmission electron microscope (TEM) analysis. Aqueous humour pathways were stained with ferritin in 6 eyeballs. By light microscopy, small vessels adjacent to the areas of scarring were the most common abnormality. Vessel density was significantly higher in operated sclera compared to normal, healthy tissue, regardless of the type of implant used. The average vessel densities were 2.18±1.48 vessels/mm2 in non-implanted sclera, 2.34±1.69 vessels/mm2 in eyes with absorbable implants, and 3.64±1.78 vessels/mm2 in eyes with non-absorbable implants. Analysis of iron distribution in ferritin-injected eyes showed a positive reaction inside new aqueous draining vessels in all groups. TEM analysis showed that the ultrastructure of new vessels matched the features of the small veins. Aqueous outflow after NPDS can be achieved through the newly formed network of small intrascleral veins. Use of non-absorbable implants significantly increases vessel density in the sclera adjacent to implanted material compared to eyes in which absorbable implants or no implants were used.
Sustained subconjunctival protein delivery using a thermosetting gel delivery system.
Rieke, Erin R; Amaral, Juan; Becerra, S Patricia; Lutz, Robert J
2010-02-01
An effective treatment modality for posterior eye diseases would provide prolonged delivery of therapeutic agents, including macromolecules, to eye tissues using a safe and minimally invasive method. The goal of this study was to assess the ability of a thermosetting gel to deliver a fluorescently labeled protein, Alexa 647 ovalbumin, to the choroid and retina of rats following a single subconjunctival injection of the gel. Additional experiments were performed to compare in vitro to in vivo ovalbumin release rates from the gel. The ovalbumin content of the eye tissues was monitored by spectrophotometric assays of tissue extracts of Alexa 647 ovalbumin from dissected sclera, choroid, and retina at time points ranging from 2 h to 14 days. At the same time points, fluorescence microscopy images of tissue samples were also obtained. Measurement of intact ovalbumin was verified by LDS-PAGE analysis of the tissue extract solutions. In vitro release of Alexa 488 ovalbumin into 37 degrees C PBS solutions from ovalbumin-loaded gel pellets was also monitored over time by spectrophotometric assay. In vivo ovalbumin release rates were determined by measurement of residual ovalbumin extracted from gel pellets removed from rat eyes at various time intervals. Our results indicate that ovalbumin concentrations can be maintained at measurable levels in the sclera, choroid, and retina of rats for up to 14 days using the thermosetting gel delivery system. The concentration of ovalbumin exhibited a gradient that decreased from sclera to choroid and to retina. The in vitro release rate profiles were similar to the in vivo release profiles. Our findings suggest that the thermosetting gel system may be a feasible method for safe and convenient sustained delivery of proteins to choroidal and retinal tissue in the posterior segments of the eye.
Sustained Subconjunctival Protein Delivery Using a Thermosetting Gel Delivery System
2010-01-01
Purpose: An effective treatment modality for posterior eye diseases would provide prolonged delivery of therapeutic agents, including macromolecules, to eye tissues using a safe and minimally invasive method. The goal of this study was to assess the ability of a thermosetting gel to deliver a fluorescently labeled protein, Alexa 647 ovalbumin, to the choroid and retina of rats following a single subconjunctival injection of the gel. Additional experiments were performed to compare in vitro to in vivo ovalbumin release rates from the gel. Methods: The ovalbumin content of the eye tissues was monitored by spectrophotometric assays of tissue extracts of Alexa 647 ovalbumin from dissected sclera, choroid, and retina at time points ranging from 2 h to 14 days. At the same time points, fluorescence microscopy images of tissue samples were also obtained. Measurement of intact ovalbumin was verified by LDS-PAGE analysis of the tissue extract solutions. In vitro release of Alexa 488 ovalbumin into 37°C PBS solutions from ovalbumin-loaded gel pellets was also monitored over time by spectrophotometric assay. In vivo ovalbumin release rates were determined by measurement of residual ovalbumin extracted from gel pellets removed from rat eyes at various time intervals. Results: Our results indicate that ovalbumin concentrations can be maintained at measurable levels in the sclera, choroid, and retina of rats for up to 14 days using the thermosetting gel delivery system. The concentration of ovalbumin exhibited a gradient that decreased from sclera to choroid and to retina. The in vitro release rate profiles were similar to the in vivo release profiles. Conclusions: Our findings suggest that the thermosetting gel system may be a feasible method for safe and convenient sustained delivery of proteins to choroidal and retinal tissue in the posterior segments of the eye. PMID:20148655
Evaluation of Tissue Interactions with Mechanical Elements of a Transscleral Drug Delivery Device
Cohen, Sarah J.; Chan, Robison V. Paul; Keegan, Mark; Andreoli, Christopher M.; Borenstein, Jeffrey T.; Miller, Joan W.; Gragoudas, Evangelos S.
2012-01-01
The goal of this work was to evaluate tissue-device interactions due to implantation of a mechanically operated drug delivery system onto the posterior sclera. Two test devices were designed and fabricated to model elements of the drug delivery device—one containing a free-spinning ball bearing and the other encasing two articulating gears. Openings in the base of test devices modeled ports for drug passage from device to sclera. Porous poly(tetrafluoroethylene) (PTFE) membranes were attached to half of the gear devices to minimize tissue ingrowth through these ports. Test devices were sutured onto rabbit eyes for 10 weeks. Tissue-device interactions were evaluated histologically and mechanically after removal to determine effects on device function and changes in surrounding tissue. Test devices were generally well-tolerated during residence in the animal. All devices encouraged fibrous tissue formation between the sclera and the device, fibrous tissue encapsulation and invasion around the device, and inflammation of the conjunctiva. Gear devices encouraged significantly greater inflammation in all cases and a larger rate of tissue ingrowth. PTFE membranes prevented tissue invasion through the covered drug ports, though tissue migrated in through other smaller openings. The torque required to turn the mechanical elements increased over 1000 times for gear devices, but only on the order of 100 times for membrane-covered gear devices and less than 100 times for ball bearing devices. Maintaining a lower device profile, minimizing microscale motion on the eye surface and covering drug ports with a porous membrane may minimize inflammation, decreasing the risk of damage to surrounding tissues and minimizing disruption of device operation. PMID:24300189
NASA Astrophysics Data System (ADS)
Belkin, Michael; Geffen, Noa; Goldenfeld, Modi; Ofir, Shay; Belkin, Avner; Assia, Ehud
2016-03-01
Developing a one-second automatic glaucoma treatment using trans-scleral laser trabeculoplasty (LTP) without a gonioscopy lens Purpose: Developing an LTP device for delivering multiple simultaneous trans-scleral applications of low energy laser irradiation to the trabecular meshwork (TM) for reducing Intraocular Pressure (IOP). Methods: Concept proof: A randomized, masked, controlled one was performed on open angle glaucoma patients. The control group underwent conventional SLT (100 laser spots through a gonioscope for 360 degrees directly on the TM). The trial group underwent irradiation by the same laser at the same irradiation parameters on the sclera overlying the TM. Topical glaucoma therapy was not changed during the 12 months trial. Feasibility trial: Using optimized laser parameters, 60 discrete applications were administered on similar locations of patients' sclera. Results: Concept proof: Trans-scleral applications: (N=15), IOP decrease from 20.21 mmHg before treatment to 16.00 (27.1%) at one year. The corresponding numbers for the control group (n=15), were 21.14 mmHg and 14.30 (23.4%). There was no statistical difference between the two groups in IOP reduction. The complications rate was significantly higher in the control group. Trial 2: IOP was reduced from an of 25.3 mmHg to 19.3 (23.7%) in the 11 patients. Conclusions: Laser coherency, lost in tissue transmission, is not required for the therapeutic effect. The new method will possibly enable treatment of angle closure glaucoma as well as simultaneous applications of all laser spots to the sclera. When used conjointly with target acquisition, will make feasible an automatic glaucoma treatment in less than one second.
Transscleral Selective Laser Trabeculoplasty Without a Gonioscopy Lens.
Geffen, Noa; Ofir, Shay; Belkin, Avner; Segev, Fani; Barkana, Yaniv; Kaplan Messas, Audrey; Assia, Ehud I; Belkin, Michael
2017-03-01
The purpose of the study was to investigate results of selective laser trabeculoplasty (SLT) performed directly on the sclera without a gonioscopy lens. Interventional case series, prospective, randomized, masked, controlled clinical trial. Setting: Meir Medical Center, Kfar-Saba, Israel. Adults with uncontrolled primary open angle or pseudoexfoliation glaucoma randomized into 2 groups. The controls underwent conventional SLT with 100 spots delivered using a gonioscopy lens for 360 degrees of the trabecular meshwork. The study group underwent irradiation using the same parameters with the laser applications administered on the perilimbal sclera. Study visits: 1 hour, 1, 7, 30, 60, 180, and 365 days postprocedure. Intraocular pressure (IOP) and side effects. Thirty adults were randomized into 2 groups. The mean (±SD) pretreatment IOP was 20.21±3.19 mm Hg for the study group (n=14) and 21.14±2.98 mm Hg for the controls (n=14; P =0.43), dropping to 15.50±3.77 and 15.00±4.08 mm Hg (P =0.74) after 6 months and to 16.00±3.31 and 14.00±2.45 mm Hg (P =0.22) after 12 months. The average IOP reduction after 6 and 12 months was 23.4% and 20.83% for the study group and 27.1% and 33.77% for the controls (P=0.528). Success (a decrease of ≥15% at 6 months with no additional medications, laser, or glaucoma surgery) was achieved in 12 (85.7%) study patients and 9 (69.2%) controls (P=0.385). Complications were mild and transient (n=30), although significantly higher in the controls (n=15; P <0.0001). SLT applied directly to the perilimbal sclera may be as efficacious as the conventional procedure for 1 year.
Borrás, Teresa; Smith, Matthew H; Buie, LaKisha K
2015-04-01
Soft tissue calcification is a pathological condition. Matrix Gla (MGP) is a potent mineralization inhibitor secreted by cartilage chondrocytes and arteries' vascular smooth muscle cells. Mgp knock-out mice die at 6 weeks due to massive arterial calcification. Arterial calcification results in arterial stiffness and higher systolic blood pressure. Intriguingly, MGP was highly abundant in trabecular meshwork (TM). Because tissue stiffness is relevant to glaucoma, we investigated which additional eye tissues use Mgp's function using knock-in mice. An Mgp-Cre-recombinase coding sequence (Cre) knock-in mouse, containing Mgp DNA plus an internal ribosomal entry site (IRES)-Cre-cassette was generated by homologous recombination. Founders were crossed with Cre-mediated reporter mouse R26R-lacZ. Their offspring expresses lacZ where Mgp is transcribed. Eyes from MgpCre/+;R26RlacZ/+ (Mgp-lacZ knock-in) and controls, 1 to 8 months were assayed for β-gal enzyme histochemistry. As expected, Mgp-lacZ knock-in's TM was intensely blue. In addition, this mouse revealed high specific expression in the sclera, particularly in the peripapillary scleral region (ppSC). Ciliary muscle and sclera above the TM were also positive. Scleral staining was located immediately underneath the choroid (chondrocyte layer), began midsclera and was remarkably high in the ppSC. Cornea, iris, lens, ciliary body, and retina were negative. All mice exhibited similar staining patterns. All controls were negative. Matrix Gla's restricted expression to glaucoma-associated tissues from anterior and posterior segments suggests its involvement in the development of the disease. Matrix Gla's anticalcification/antistiffness properties in the vascular tissue, together with its high TM and ppCS expression, place this gene as a strong candidate for TM's softness and sclera's stiffness regulation in glaucoma.
Expression Profile of the Integrin Receptor Subunits in the Guinea Pig Sclera.
Wang, Kevin K; Metlapally, Ravikanth; Wildsoet, Christine F
2017-06-01
The ocular dimensional changes in myopia reflect increased scleral remodeling, and in high myopia, loss of scleral integrity leads to biomechanical weakening and continued scleral creep. As integrins, a type of cell surface receptors, have been linked to scleral remodeling, they represent potential targets for myopia therapies. As a first step, this study aimed to characterize the integrin subunits at the messenger RNA level in the sclera of the guinea pig, a more recently added but increasingly used animal model for myopia research. Primers for α and β integrin subunits were designed using NCBI/UCSC Genome Browser and Primer3 software tools. Total RNA was extracted from normal scleral tissue and isolated cultured scleral fibroblasts, as well as liver and lung, as reference tissues, all from guinea pig. cDNA was produced by reverse transcription, PCR was used to amplify products of predetermined sizes, and products were sequenced using standard methods. Guinea pig scleral tissue expressed all known integrin alpha subunits except αD and αE. The latter integrin subunits were also not expressed by cultured guinea pig scleral fibroblasts; however, their expression was confirmed in guinea pig liver. In addition, isolated cultured fibroblasts did not express integrin subunits αL, αM, and αX. This difference between results for cultured cells and intact sclera presumably reflects the presence in the latter of additional cell types. Both guinea pig scleral tissue and isolated scleral fibroblasts expressed all known integrin beta subunits. All results were verified through sequencing. The possible contributions of integrins to scleral remodeling make them plausible targets for myopia prevention. Data from this study will help guide future ex vivo and in vitro studies directed at understanding the relationship between scleral integrins and ocular growth regulation in the guinea pig model for myopia.
Distribution of photon absorption rates across the rat retina.
Williams, T P; Webbers, J P; Giordano, L; Henderson, R P
1998-04-15
1. An investigation into the distribution of light intensity across the rat retina was carried out on excised, intact rat eyes exposed to Ganzfeld illumination from a helium-neon laser (543 nm). 2. Some of the light entering the eyes exits through the sclera where its intensity can be monitored with an optical 'pick-up' that samples the intensity coming from a small region of external sclera and underlying retina. The spatial resolution of the pick-up is such that it samples light that has passed through ca 2 % of the rods in the rat eye. 3. Some of the laser light is absorbed by the rod pigment, rhodopsin, which gradually bleaches. Bleaching in the retina, in turn, causes an exponential increase in intensity emanating from the sclera. By monitoring this intensity increase, we are able to measure two important parameters in a single bleaching run: the local rhodopsin concentration and the local intensity falling on the rods. 4. With an ocular transmission photometer, we have measured both the local intensity and the local rhodopsin concentration across wide regions of rat retina. Both pigmented and albino rats were studied. 5. The distributions of rhodopsin and intensity were both nearly uniform; consequently, the product, (rhodopsin concentration) x (intensity), was similarly nearly equal across the retina. This means that the initial rate of photon absorption is about the same at all retinal locations. 6. Interpreted in terms of photostasis (the regulation of daily photon catch), this means that the rate of photon absorption is about the same in each rod, viz. 14 400 photons absorbed per rod per second. Since this rate of absorption is sufficient to saturate the rod, one possible purpose of photostasis is to maintain the rod system in a saturated state during daylight hours.
What is new in genetics and osteogenesis imperfecta classification?
Valadares, Eugênia R; Carneiro, Túlio B; Santos, Paula M; Oliveira, Ana Cristina; Zabel, Bernhard
2014-01-01
Literature review of new genes related to osteogenesis imperfecta (OI) and update of its classification. Literature review in the PubMed and OMIM databases, followed by selection of relevant references. In 1979, Sillence et al. developed a classification of OI subtypes based on clinical features and disease severity: OI type I, mild, common, with blue sclera; OI type II, perinatal lethal form; OI type III, severe and progressively deforming, with normal sclera; and OI type IV, moderate severity with normal sclera. Approximately 90% of individuals with OI are heterozygous for mutations in the COL1A1 and COL1A2 genes, with dominant pattern of inheritance or sporadic mutations. After 2006, mutations were identified in the CRTAP, FKBP10, LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, WNT1, BMP1, and TMEM38B genes, associated with recessive OI and mutation in the IFITM5 gene associated with dominant OI. Mutations in PLS3 were recently identified in families with osteoporosis and fractures, with X-linked inheritance pattern. In addition to the genetic complexity of the molecular basis of OI, extensive phenotypic variability resulting from individual loci has also been documented. Considering the discovery of new genes and limited genotype-phenotype correlation, the use of next-generation sequencing tools has become useful in molecular studies of OI cases. The recommendation of the Nosology Group of the International Society of Skeletal Dysplasias is to maintain the classification of Sillence as the prototypical form, universally accepted to classify the degree of severity in OI, while maintaining it free from direct molecular reference. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.
Yang, Hongli; Downs, J. Crawford; Sigal, Ian A.; Roberts, Michael D.; Thompson, Hillary; Burgoyne, Claude F.
2010-01-01
Purpose To characterize optic nerve head (ONH) connective tissue deformation following acute (15 or 30 minutes) intraocular pressure (IOP) elevation within six adult normal monkeys using 3-D histomorphometry. Methods Trephinated ONH and peripapillary sclera from both eyes of six monkeys, each perfusion fixed with one eye at IOP 10 mmHg and the other at IOP 30 or 45 mmHg by anterior chamber manometer were serial sectioned, 3-D reconstructed, 3-D delineated and quantified using standard parameters. For each monkey, inter-eye differences (high IOP eye minus IOP 10 eye) for each parameter were calculated and compared by ANOVA and EPIDmax both overall and regionally. EPIDmax deformations for each parameter were defined to be those statistically significant differences that exceeded the maximum physiologic inter-eye difference within six bilaterally normal monkeys of a previous report. Results Regional EPIDmax laminar thinning, posterior bowing of the peripapillary sclera, thinning and expansion of the scleral canal were present in most high IOP eyes and were colocalized in those demonstrating the most deformation. Laminar deformation was minimal and not only posterior but in some cases anterior in the high IOP eyes. No increase in deformation was seen in the IOP-45 versus the IOP-30 eyes. Conclusion ONH connective tissue alterations following acute IOP elevation involve regional thinning, stretching and deformation of the lamina cribrosa and peripapillary sclera which are minimal to modest in magnitude. The time-dependent character of these alterations, as well as their compressive, expansile, and shear effects on the contained axons, astrocytes, laminar and posterior ciliary circulations remain to be determined. PMID:19628739
21 CFR 886.4350 - Manual ophthalmic surgical instrument.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Manual ophthalmic surgical instrument. 886.4350 Section 886.4350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... suturing needle, lachrymal probe, trabeculotomy probe, cornea-sclera punch, ophthalmic retractor...
[Black urine or black sclera of the eyes? Consider alkaptonuria].
Gubbels, Nanda P; Sijbrand, Merijn H; Onstenk, Ron
2014-01-01
Alkaptonuria is a rare metabolic disorder due to a defect in the gene for homogentisic acid oxidase. This results in an accumulation of homogentisic acid, which leads to the deposit of pigment in the connective tissue in the body. This causes problems and symptoms in various organ systems, such as early artropathy, dark-coloured urine, black sclerae, dark-coloured aortic valves and an increased risk of kidney stones and gall stones. Various specialists may see patients with this disease. The diagnosis is often missed. We describe a 69-year-old woman who underwent surgery due to joint problems, which showed up black cartilage. It turned out that for many years she had also had eye and heart problems. Not until later in life was she diagnosed with alkaptonuria. There is no curative treatment for alkaptonuria at the moment. Early recognition of the disease can increase the quality of life. Preventative check-ups and guidance are also therefore necessary.
Lax ligament syndrome in children associated with blue sclera and bat ears.
Howard, F M
1990-01-01
The child that is slow to walk causes concern. When cerebral palsy, mental retardation and muscular dystrophy have been excluded, what remains? Thirty five children (19 boys and 16 girls) with hypermobile joints, blue sclera and bat ears (the 'lax ligament syndrome') were referred by general practitioners to a general paediatric outpatient clinic over two years. Three were referred in the first three months of life because of clicking hips; 14 children aged one to two years, had delayed milestones of motor development and exhibited bottom shuffling; 10 children aged four to five years presented with 'growing pains' or 'funny gait' and eight older children had multiple minor complaints. The lax ligament syndrome is a comparatively common mild collagenopathy. It may well come to light on routine surveillance in general practice. It is dominantly inherited and improves with time; management is therefore expectant and symptomatic. A firm and reassuring diagnosis can be given which saves both anxiety and investigations. Images Figure 1. PMID:2117944
Nominal Ocular Dazzle Distance (NODD)
2015-02-23
retinal areas [14–16]. There is also a smaller contribution from the ocular wall [17], comprising the sclera and the iris . These internal scatter...retina, forma - tion and duration of afterimages in the case of Class 1 laser products, and disability glare arising from high-brightness light emitting
PROGRAMMED CELL DEATH IN EXTRAOCULAR MUSCLE TENDON/SCLERA PRECURSORS
Abstract
Purpose: This study was designed to examine the occurrence of natural cell death in the periocular mesenchyme of mouse embryos.
Methods: Vital staining with LysoTracker Red and Nile blue sulphate as well as terminal nick end labeling (TUNEL) were utiliz...
NASA Astrophysics Data System (ADS)
Aryal, Prakash
The TG-43 dosimetry parameters of the Advantage(TM) 125I model IAI-125A brachytherapy seed were studied. An investigation using modern MCNP radiation transport code with updated cross-section libraries was performed. Twelve different simulation conditions were studied for a single seed by varying the coating thickness, mass density, photon energy spectrum and cross-section library. The dose rate was found to be 6.3% lower at 1 cm in comparison to published results. New TG-43 dosimetry parameters are proposed. The dose distribution for a brachytherapy eye plaque, model EP917, was investigated, including the effects of collimation from high-Z slots. Dose distributions for 26 slot designs were determined using Monte Carlo methods and compared between the published literature, a clinical treatment planning system, and physical measurements. The dosimetric effect of the composition and mass density of the gold backing was shown to be less than 3%. Slot depth, width, and length changed the central axis (CAX) dose distributions by < 1% per 0.1 mm in design variation. Seed shifts in the slot towards the eye and shifts of the 125I-laden silver rod within the seed had the greatest impact on the CAX dose distribution, changing it by 14%, 9%, 4.3%, and 2.7% at 1, 2, 5, and 10 mm, respectively, from the inner scleral surface. The measured, full plaque slot geometry delivered 2.4% +/- 1.1% higher dose along the plaque's CAX than the geometry provided by the manufacturer and 2.2%+/-2.3% higher than Plaque Simulator(TM) (PS) treatment planning software (version 5.7.6). The D10 for the simulated tumor, inner sclera, and outer sclera for the measured slot plaque to manufacturer provided slot design was 9%, 10%, and 19% higher, respectively. In comparison to the measured plaque design, a theoretical plaque having narrow and deep slots delivered 30%, 37%, and 62% lower D 10 doses to the tumor, inner sclera, and outer sclera, respectively. CAX doses at --1, 0, 1, and 2 mm were also lower by a factor of 2.6, 1.72, 1.50, and 1.39, respectively. The study identified substantial sensitivity of the EP917 plaque dose distributions to slot design. KEYWORDS: Monte Carlo methods, dosimetry, 125I, TG-43, eye plaque brachytherapy.
Oculocardiac reflex in a dog caused by a choroidal melanoma with orbital extension.
Steinmetz, Andrea; Ellenberger, Kristin; März, Imke; Ludewig, Eberhard; Oechtering, Gerhard
2012-01-01
A 7 yr old mixed-breed dog was presented with a choroidal melanoma of the left eye that had penetrated the sclera, producing an orbital mass. Bradycardia was detected on auscultation. The bradycardia resolved after exenteration of the orbit and was therefore presumed to be associated with the oculocardiac reflex.
Injectable suture device for intraocular lens fixation.
Smith, Jesse M; Erlanger, Michael; Olson, Jeffrey L
2015-12-01
We describe a surgical technique for scleral fixation of a posterior chamber intraocular lens (PC IOL) using a 24-gauge injectable polypropylene suture delivery system. A 3-piece PC IOL is inserted into the anterior chamber of the eye. Two sclerotomies are made 1.5 mm posterior to the limbus using a microvitreoretinal blade. The 24-gauge injector delivers a preformed suture loop into the eye with the double-armed needles still external to the eye. Each polypropylene IOL haptic is directed through the loop using microforceps. The suture loop is tightened around the haptic, and the attached needles are used to fixate the IOL to the sclera and close the sclerotomies simultaneously. This technique has been used in an ex vivo porcine eye and in an aphakic patient. In the latter, the IOL was quickly fixated to the sclera and maintained a stable position postoperatively. Dr. Olson has a patent pending for the device described in this article. No other author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.
Bravo, Jaime F; Wolff, Carlos
2006-02-01
To demonstrate the high frequency and lack of diagnosis of joint hypermobility syndrome (JHS) and the seriousness of vascular Ehlers-Danlos syndrome (VEDS). Two hundred forty-nine Chilean patients with hereditary disorders of the connective tissues (CTDs) and 64 control subjects were evaluated for the diagnoses of JHS and VEDS using the validated Brighton criteria, as compared with the traditional Beighton score. In addition, the presence of blue sclera was determined, with the degree of intensity graded as mild, moderate, or marked. The frequency of hereditary CTDs was 35%, with diagnoses of JHS in 92.4% of subjects, VEDS in 7.2%, and osteogenesis imperfecta in 0.4%. The Beighton score proved to be insufficient for the diagnosis of JHS (35% of subjects had a negative score), whereas the Brighton criteria yielded positive findings (a diagnosis of JHS) in 39% of control subjects. Blue sclera was frequent, being identified in 97% of JHS patients and 94% of VEDS patients. Moderate osteopenia/osteoporosis was observed in 50% of patients with VEDS and 26% of those with JHS. Dysautonomia, dyslipidemia, and scoliosis were more frequent in VEDS patients than in JHS patients. The typical JHS facial appearance and the "hand holding the head sign" were identified. Raynaud's phenomenon was extremely rare in JHS patients (2%). Ruptured uterus and cerebral aneurysm occurred in 12% and 6% of VEDS patients, respectively. Spontaneous pneumothorax was more frequent in VEDS patients (11%) than in JHS patients (0.9%). JHS is very frequent but usually undiagnosed. The Beighton score is an insufficient method for JHS diagnosis. We recommend that physicians learn to recognize the typical facial features of JHS and be able to identify blue sclera. We also propose that validated hypermobility criteria be routinely used. Further research is needed to determine why the prevalence of JHS is so high in Chile.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Aryal, P; Molloy, JA; Rivard, MJ
Purpose: To investigate the effect of plaque design and radionuclides on eye plaque dosimetry. Methods: The Monte Carlo N-particle Code version 6 (MCNP6) was used for radiation transport simulations. The 14 mm and 16 mm diameter COMS plaques and the model EP917 plaque were simulated using brachytherapy seeds containing I-125, Pd-103, and Cs-131 radionuclides. The origin was placed at the scleral inner surface. The central axis (CAX) doses of both COMS plaques at −1 mm, 0 mm, 1 mm, 2 mm, 5 mm, 10 mm, 15 mm, 20 mm, and 22.6 mm were compared to the model EP917 plaque. Dosemore » volume histograms (DVHs) were also created for both COMS plaques for the tumor and outer sclera then compared to results for the model EP917 plaque. Results: For all radionuclides, the EP917 plaque delivered higher dose (max 343%) compared to the COMS plaques, except for the 14 mm COMS plaque with Cs-131 at 1 mm and 2 mm depths from outer sclera surface. This could be due to source design. For all radionuclides, the 14 mm COMS plaque delivered higher doses compared to the 16 mm COMS plaque for the depths up to 5 mm. Dose differences were not significant beyond depths of 10 mm due to ocular lateral scatter for the different plaque designs. Tumor DVHs for the 16 mm COMS plaque with Cs-131 provided better dose homogeneity and conformity compared to other COMS plaques with I-125 and Pd-103. Using Pd-103, DVHs for the 16 mm COMS plaque delivered less dose to outer sclera compared to other plaques. Conclusion: This study identified improved tumor homogeneity upon considering radionuclides and plaque designs, and found that scleral dose with the model EP917 plaque was higher than for the 16 mm COMS plaque for all the radionuclides studied.« less
SCLERAL AND CHOROIDAL THICKNESS IN SECONDARY HIGH AXIAL MYOPIA.
Shen, Ling; You, Qi Sheng; Xu, Xiaolin; Gao, Fei; Zhang, Zhibao; Li, Bin; Jonas, Jost B
2016-08-01
To assess differences in scleral and choroidal thickness between eyes with secondary high axial myopia caused by congenital glaucoma, eyes with primary high axial myopia, and nonhighly myopic eyes. The study consisted of 301 Chinese individuals with a mean age of 23.9 ± 22.6 years and mean axial length of 24.8 ± 4.2 mm. It included the "secondary highly myopic group" (SHMG) because of congenital glaucoma (n = 20 eyes; axial length >26.0 mm), the "primary highly myopic group" (PHMG) (n = 73; axial length >26.0 mm), and the remaining nonhighly myopic group (NHMG). The secondary highly myopic group versus the primary highly myopic group had significantly thinner sclera in the pars plana region (343 ± 71 μm versus 398 ± 83 μm; P = 0.006), whereas scleral thickness in other regions did not differ significantly between both highly myopic groups and was significantly thinner in both highly myopic groups than in the NHMG. Mean total scleral volume did not differ significantly (P > 0.20) between any group (SHMG: 659 ± 106 μm; PHMG: 667 ± 128 μm; NHMG: 626 ± 135 μm). Choroidal thickness was significantly thinner in both highly myopic groups than in the NHMG, with no significant differences between both highly myopic groups. Choroidal volume did not differ significantly (P > 0.40) between any of the groups (SHMG: 43 ± 12 μm; PHMG: 43 ± 13 μm; NHMG: 46 ± 17 μm). In secondary high axial myopia, the sclera gets thinner anterior and posterior to the equator; whereas in primary high axial myopia, scleral thinning is predominantly found posterior to the equator. Because volume of sclera and choroid did not differ between any group, scleral and choroidal thinning in myopia may be due to a rearrangement of tissue and not due to the new formation of tissue.
Nickla, D L; Wildsoet, C; Wallman, J
1997-04-01
It has been demonstrated that chick eye growth compensates for defocus imposed by spectacle lenses: the eye elongates in response to hyperopic defocus imposed by negative lenses and slows its elongation in response to myopic defocus imposed by positive lenses. We ask whether the synthesis of scleral extracellular matrix, specifically glycosaminoglycans, changes in parallel with the changes in ocular elongation. In addition, there is a choroidal component to compensation for spectacle lenses; the choroid thickens in response to myopic defocus and thins in response to hyperopic defocus. We ask whether choroidal glycosaminoglycan synthesis changes in parallel with changes in choroidal thickness. Chicks wore either a +15 diopter (D) or -15 D spectacle lens over one eye, or they wore one lens of each power over each eye for 5 days. At the end of this period, we measured refractive errors and ocular dimensions by refractometry and A-scan ultrasonography, respectively. Pieces of the scleras and choroids from these eyes were put into culture and the synthesis of glycosaminoglycans was assessed by measuring the incorporation of radioactive inorganic sulfur. We here report that the compensatory modulation of the length of the eye involves changes in the synthesis of glycosaminoglycans in the sclera, with synthesis increasing in eyes wearing -15 D spectacles lenses and decreasing in eyes wearing +15 D lenses. In addition, changes in the synthesis of glycosaminoglycans in the choroid are correlated with changes in choroidal thickness: eyes wearing +15 D lenses develop thicker choroids and these choroids synthesize more glycosaminoglycans than choroids from eyes wearing -15 D lenses. Changes in scleral glycosaminoglycan synthesis accompany lens-induced changes in the length of the eye. Furthermore, changes in the thickness of the choroid are also associated with changes in the synthesis of glycosaminoglycans. These results are consistent with the regulation of the growth of the eye being bidirectional, and with the retina being able to sense the sign of defocus.
Biomechanical simulation of eye-airbag impacts during vehicle accidents.
Shirzadi, Hooman; Zohoor, Hassan; Naserkhaki, Sadegh
2018-06-01
Airbags are safety devices in vehicles effectively suppressing passengers' injuries during accidents. Although there are still many cases of eye injuries reported due to eye-airbag impacts in recent years. Biomechanical approaches are now feasible and can considerably help experts to investigate the issue without ethical concerns. The eye-airbag impact-induced stresses/strains in various components of the eye were found to investigate the risk of injury in different conditions (impact velocity and airbag pressure). Three-dimensional geometry of the eyeball, fat and bony socket as well as the airbag were developed and meshed to develop a finite element model. Nonlinear material properties of the vitreous body and sclera were found through the in vitro tests on ovine samples and for the other components were taken from the literature. The eye collided the airbag due to the velocity field in the dynamic explicit step in Abaqus. Results of compression tests showed a nonlinear curve for vitreous body with average ultimate stress of 22 (18-25) kPa. Tensile behavior of sclera was viscoelastic nonlinear with ultimate stresses changing from 2.51 (2.3-2.7) to 4.3 (4-4.6) MPa when loading strain rate increased from 10 to 600 mm/min. Sclera, ciliary body, cornea and lens were the eye components with highest stresses (maximum stress reached up to 9.3 MPa). Cornea, retina and choroid experienced the highest strains with the maximum up to 14.1%. According to the previously reported injury criteria for cornea, it was at high risk of injury considering both stress and strains. Reduced pressure of the airbag was beneficial decreased stress of all components. Comprehensive investigations in this area can disclose biomechanical behavior of the eye during eye-airbag impact. Effective guidelines can be drawn for airbag design for instance the airbag pressure which reduces risk of eye injury.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ionin, Andrey A.; Kozhushko, Svetlana E.; Kudryashov, Sergey I.
We have successfully fabricated in vitro femtosecond laser micro-incisions inside cornea and--for the first time--inside sclera mildly pre-cleared by a biocompatible and clinically safe (non-toxic) natural agent (replacive refractive index-matching 40%-glucose solution in water), with the tissues taken as fresh cool cuts of human cadaver eyes, and reported on basic operational conditions of the micro-surgical procedures.
Damarla, Nirupama; Linga, Prathima; Goyal, Mallika; Tadisina, Sanjay Reddy; Reddy, G Satyanarayana; Bommisetti, Hymavathi
2017-06-01
Alkaptonuria is a rare inborn error of metabolism with autosomal recessive inheritance with a mutation in homogentisate 1,2-dioxygenase. It results in accumulation of homogentisic acid in connective tissues (ochronosis). Most common ocular manifestations are bluish-black discoloration of the conjunctiva, cornea, and sclera. In this case report, a 39-year-old Indian male patient with additional ocular features in the retina is described.
Damarla, Nirupama; Linga, Prathima; Goyal, Mallika; Tadisina, Sanjay Reddy; Reddy, G Satyanarayana; Bommisetti, Hymavathi
2017-01-01
Alkaptonuria is a rare inborn error of metabolism with autosomal recessive inheritance with a mutation in homogentisate 1,2-dioxygenase. It results in accumulation of homogentisic acid in connective tissues (ochronosis). Most common ocular manifestations are bluish-black discoloration of the conjunctiva, cornea, and sclera. In this case report, a 39-year-old Indian male patient with additional ocular features in the retina is described. PMID:28643719
The supraciliary space as a suitable pathway for glaucoma surgery: Ho-hum or home run?
Figus, Michele; Posarelli, Chiara; Passani, Andrea; Albert, Timothy G; Oddone, Francesco; Sframeli, Angela Tindara; Nardi, Marco
The supraciliary space is a physiological route for aqueous humor outflow located anteriorly between the outer surface of the ciliary body and the internal surface of the sclera. Posteriorly, the suprachoroidal space is located between the choroid and the internal surface of the sclera. These spaces have been targeted as suitable and helpful pathways for glaucoma treatment, alternatives to the traditional subconjunctival space. The subconjunctival surgical pathway is affected by several limitations such as poor cosmesis, a lifetime risk for endophthalmitis, and an unpredictable wound healing response. Because of these limitations, the supraciliary space has gained growing interest as a possible target for new glaucoma drainage devices such as: Gold Micro Shunt (SOLX Inc.; Waltham, MA, USA), iStent Supra (Glaukos Corporation, Laguna Hills, CA, USA), CyPass Micro-Stent (Transcend Medical Inc., Menlo Park, CA, USA), Aquashunt (OPKO health Inc., Miami, FL, USA), STARflo (iSTAR Medical, Isnes, Belgium), and Esnoper-Clip implant (AJL Ophthalmics, Álava, Spain). We review the current literature concerning the supraciliary space to evaluate its safety and efficacy as a suitable pathway for glaucoma surgical treatment. Copyright © 2017 Elsevier Inc. All rights reserved.
The role of microRNAs in myopia.
Jiang, Bo; Huo, Yanan; Gu, Yangshun; Wang, Jianyong
2017-01-01
In recent years, research on microRNAs (miRNAs) has become popular because of the critical role these macromolecules play in post-transcriptional gene regulation. Recent efforts have been made to identify miRNAs and their possible roles in myopia. The aim of this review was to summarize the expression and function of miRNAs during the development of myopia. In this article, we reviewed the current research on the mechanisms that regulate miRNA expression, the potential for miRNAs as a diagnostic biomarker for myopia, and the mechanisms by which miRNAs promote the development of myopia. We also discussed the miRNA expression profiles in human fetal sclera. We summarized the miRNA expression profiles in myopia, including miR-328, miR-184, miR-29a, and miR-let-7i, and also the miRNA expression profiles in fetal sclera, including miR-214, miR-let-7, miR-103, miR-107, miR-29b, miR-328, and miR-98. Such knowledge could lead to more precise diagnosis, prognosis, and response predictions for future treatments for myopia, and the pace of discovery is expected to accelerate dramatically in the near future.
Chakraborty, Nilay; Wang, Mian; Solocinski, Jason; Kim, Wonsuk; Argento, Alan
2016-01-01
This work presents an optospectroscopic characterization technique for soft tissue microstructure using site-matched confocal Raman microspectroscopy and polarized light microscopy. Using the technique, the microstructure of soft tissue samples is directly observed by polarized light microscopy during loading while spatially correlated spectroscopic information is extracted from the same plane, verifying the orientation and arrangement of the collagen fibers. Results show the response and orientation of the collagen fiber arrangement in its native state as well as during tensile and compressive loadings in a porcine sclera model. An example is also given showing how the data can be used with a finite element program to estimate the strain in individual collagen fibers. The measurements demonstrate features that indicate microstructural reorganization and damage of the sclera's collagen fiber arrangement under loading. The site-matched confocal Raman microspectroscopic characterization of the tissue provides a qualitative measure to relate the change in fibrillar arrangement with possible chemical damage to the collagen microstructure. Tests and analyses presented here can potentially be used to determine the stress-strain behavior, and fiber reorganization of the collagen microstructure in soft tissue during viscoelastic response.
New eye phantom for ophthalmic surgery
NASA Astrophysics Data System (ADS)
Fogli, Gessica; Orsi, Gianni; De Maria, Carmelo; Montemurro, Francesca; Palla, Michele; Rizzo, Stanislao; Vozzi, Giovanni
2014-06-01
In this work, we designed and realized a new phantom able to mimic the principal mechanical, rheological, and physical cues of the human eye and that can be used as a common benchmark to validate new surgical procedures, innovative vitrectomes, and as a training system for surgeons. This phantom, in particular its synthetic humor vitreous, had the aim of reproducing diffusion properties of the natural eye and can be used as a system to evaluate the pharmacokinetics of drugs and optimization of their dose, limiting animal experiments. The eye phantom was built layer-by-layer starting from the sclera up to the retina, using low cost and easy to process polymers. The validation of the phantom was carried out by mechanical characterization of each layer, by diffusion test with commercial drugs into a purposely developed apparatus, and finally by a team of ophthalmic surgeons. Experiments demonstrated that polycaprolactone, polydimethylsiloxane, and gelatin, properly prepared, are the best materials to mimic the mechanical properties of sclera, choroid, and retina, respectively. A polyvinyl alcohol-gelatin polymeric system is the best for mimicking the viscosity of the human humor vitreous, even if the bevacizumab half-life is lower than in the human eye.
Gao, Hong; Frost, Michael R; Siegwart, John T; Norton, Thomas T
2011-04-12
To increase our understanding of the mechanisms that remodel the sclera during the development of lens-induced myopia, when the sclera responds to putative "go" signals of retinal origin, and during recovery from lens-induced myopia, when the sclera responds to retinally-derived "stop" signals. Seven groups of tree shrews were used to examine mRNA levels during minus lens compensation and recovery. Starting 24 days after eye opening (days of visual experience [VE]) lens compensation animals wore a monocular -5D lens for 1, 4, or 11 days. Recovery animals wore the -5D lens for 11 days, which was then removed for 1 or 4 days. Normal animals were examined at 24 and 38 days of VE. All groups contained 8 animals. Scleral mRNA levels were examined in the treated and contralateral control eyes with quantitative real-time polymerase chain reaction (qPCR) for 27 genes divided into four categories: 1) signaling molecules, 2) matricellular proteins, 3) metalloproteinases (MPs) and tissue inhibitors of metalloproteinases (TIMPs), and 4) cell adhesion and other proteins. Four groups (n=5 per group) were used to examine protein levels. One group wore a -5D lens for 4 days. A second group recovered for 4 days after 11 days of -5D lens treatment. Two groups were used to examine age-matched normal protein levels at 28 and 39 days of VE. The levels of six scleral proteins that showed differential mRNA expression were examined with quantitative western blots. Nineteen of the genes showed differential (treated eye versus control eye) expression of mRNA levels in at least one group of animals. Which genes showed differential expression differed after 1 and 4 days of compensation and after 1 or 4 days of recovery. The mRNA level for one gene, a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1), was upregulated in the treated eyes after 1 day of compensation. After 4 days, transforming growth factor beta receptor 3 (TGFBR3), transforming growth factor-beta-induced protein ig-h3 (TGFBI), and matrix metalloproteinase 14 (MMP14) mRNA levels were upregulated. Downregulated were mRNA levels for transforming growth factor beta-1 (TGFB1), transforming growth factor beta-2 (TGFB2), thrombospondin 1 (THBS1), tenascin (TNC), osteonectin (SPARC), osteopontin (SPP1), tissue inhibitor of metalloproteinases 3 (TIMP3), and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5). After 11 days of lens wear, there was no differential expression. During recovery, after 1 day, treated-eye mRNA downregulation was found for TGFB2, TGFBR1, TGFBR2, TGFBR3, SPARC, ADAMTS1, ADAMTS5, syndecan 4 (SDC4), and collagen type VI, alpha 1 (COL6A1). After 4 days, TGFB1, TGFB2, TGFB3, THBS2, and TIMP3 mRNA levels were upregulated in the recovering eye. Significant downregulation, relative to normal eyes, was found in both the control and treated eyes for most genes after 1 day of compensation; a similar decrease was found, compared to lens-compensated eyes, after one day of recovery. Protein levels for THBS1 showed positive correlation with the differential mRNA levels and TGFBR3 showed a negative correlation. No differential protein expression was found for TGFB2, TGFBI, MMP14, and TIMP3. The different patterns of differential mRNA expression during minus lens compensation (hyperopia) and recovery (myopia) show that scleral fibroblasts distinguish between "go" and "stop" conditions. There is evidence of binocular global downregulation of genes at the start of both lens wear and recovery. As additional information accumulates about changes in gene expression that occur during compensation and recovery the "signature" of differential changes may help us to understand in more detail how the sclera responds in "go" and "stop" conditions.
Femtosecond Laser Micro-structuring Of Transparent Materials And Its Ophthalmologic Applications
NASA Astrophysics Data System (ADS)
Ionin, Andrey A.; Kozhushko, Svetlana E.; Kudryashov, Sergey I.; Seleznev, Leonid V.; Sinitsyn, Dmitry V.; Zakharov, Stanislav D.; Alekhin, Alexander I.; Kourylyova, Irina M.; Kuz'min, Kirill K.; Likhvantseva, Vera G.; Samoylov, Michail V.
2010-10-01
We have successfully fabricated in vitro femtosecond laser micro-incisions inside cornea and—for the first time—inside sclera mildly pre-cleared by a biocompatible and clinically safe (non-toxic) natural agent (replacive refractive index-matching 40%-glucose solution in water), with the tissues taken as fresh cool cuts of human cadaver eyes, and reported on basic operational conditions of the micro-surgical procedures.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ciller, Carlos, E-mail: carlos.cillerruiz@unil.ch; Ophthalmic Technology Group, ARTORG Center of the University of Bern, Bern; Centre d’Imagerie BioMédicale, University of Lausanne, Lausanne
Purpose: Proper delineation of ocular anatomy in 3-dimensional (3D) imaging is a big challenge, particularly when developing treatment plans for ocular diseases. Magnetic resonance imaging (MRI) is presently used in clinical practice for diagnosis confirmation and treatment planning for treatment of retinoblastoma in infants, where it serves as a source of information, complementary to the fundus or ultrasonographic imaging. Here we present a framework to fully automatically segment the eye anatomy for MRI based on 3D active shape models (ASM), and we validate the results and present a proof of concept to automatically segment pathological eyes. Methods and Materials: Manualmore » and automatic segmentation were performed in 24 images of healthy children's eyes (3.29 ± 2.15 years of age). Imaging was performed using a 3-T MRI scanner. The ASM consists of the lens, the vitreous humor, the sclera, and the cornea. The model was fitted by first automatically detecting the position of the eye center, the lens, and the optic nerve, and then aligning the model and fitting it to the patient. We validated our segmentation method by using a leave-one-out cross-validation. The segmentation results were evaluated by measuring the overlap, using the Dice similarity coefficient (DSC) and the mean distance error. Results: We obtained a DSC of 94.90 ± 2.12% for the sclera and the cornea, 94.72 ± 1.89% for the vitreous humor, and 85.16 ± 4.91% for the lens. The mean distance error was 0.26 ± 0.09 mm. The entire process took 14 seconds on average per eye. Conclusion: We provide a reliable and accurate tool that enables clinicians to automatically segment the sclera, the cornea, the vitreous humor, and the lens, using MRI. We additionally present a proof of concept for fully automatically segmenting eye pathology. This tool reduces the time needed for eye shape delineation and thus can help clinicians when planning eye treatment and confirming the extent of the tumor.« less
Zhou, Xiangtian; Ji, Fengtao; An, Jianhong; Zhao, Fuxin; Shi, Fanjun; Huang, Furong; Li, Yuan; Jiao, Shiming; Yan, Dongsheng; Chen, Xiaoyan; Chen, JiangFan
2012-01-01
Purpose To investigate whether myopia development is associated with changes of scleral DNA methylation in cytosine-phosphate-guanine (CpG) sites in the collagen 1A1 (COL1A1) promoter and messenger RNA (mRNA) levels following murine form deprivation myopia. Methods Fifty-seven C57BL/6 mice (postnatal day 23) were randomly assigned to four groups: (1) monocular form deprivation (MD) in which a diffuser lens was placed over one eye for 28 days; (2) normal controls without MD; (3) MD recovery in which the diffuser lens was removed for seven days; and (4) MD recovery normal controls. The DNA methylation pattern in COL1A1 promoter and exon 1 was determined by bisulfite DNA sequencing, and the COL1A1 mRNA level in sclera was determined by quantitative PCR. Results MD was found to induce myopia in the treated eyes. Six CpG sites in the promoter and exon 1 region of COL1A1 were methylated with significantly higher frequency in the treated eyes than normal control eyes (p<0.05), with CpG island methylation in MD-contralateral eyes being intermediate. Consistent with the CpG methylation, scleral COL1A1 mRNA was reduced by 57% in the MD-treated eyes compared to normal controls (p<0.05). After seven days of MD recovery, CpG methylation was significantly reduced (p=0.01). The methylation patterns returned to near normal level in five CpG sites, but the sixth was hypomethylated compared to normal controls. Conclusions In parallel with the development of myopia and the reduced COL1A1 mRNA, the frequency of methylation in CpG sites of the COL1A1 promoter/exon 1 increased during MD and returned to near normal during recovery. Thus, hypermethylation of CpG sites in the promoter/exon 1 of COL1A1 may underlie reduced collagen synthesis at the transcriptional level in myopic scleras. PMID:22690110
Szurman, Peter; Januschowski, Kai; Boden, Karl Thomas; Seuthe, Anna-Maria
2018-02-01
Our purpose was both to introduce the new technique of suprachoroidal drainage with collagen sheet implantation as a novel technique of non-penetrating glaucoma surgery and to present first results of a prospective pilot study. A superficial rectangular sclera flap of half-scleral thickness sized 4 × 4.5 mm is dissected anteriorly until clear cornea. Then, a second scleral flap is created underneath the first one sized 3.5x4mm and is cut down full-thickness to the choroid exposing the suprachoroidal space. The flap is then bluntly prepared until the scleral spur is reached. Sharp dissection above the sclera spur exposes Schlemm's canal, which is located directly anteriorly. Schlemm's canal is unroofed, juxtacanalicular meshwork is peeled and the deep flap is cut off at its base. An absorbable collagen sheet (Ologen®, Dahlhausen, Cologne, Germany) is placed into the suprachoroidal space at the level of the ciliary body, and the superficial sclera flap is sutured tightly to prevent leakage. We prospectively analyzed 65 eyes that underwent suprachoroidal drainage with collagen sheet implantation. Mean reduction of intraocular pressure after 3 months was 35.1% (from 21.0 ± 4.3 mmHg to 13.5 ± 3.4 mmHg)(p < 0.01) and after 12 months 35.6% (from 21.0 ± 4.3 mmHg to 13.5 ± 3.0 mmHg)(p < 0.01). The number of topical IOP-reducing medication decreased significantly from 3.5 ± 0.7 to 0.6 ± 0.9 and to 0.9 ± 1.1 after 3 and 12 months, respectively (p < 0.01). No serious complications occurred. Suprachoroidal drainage with collagen sheet implantation seems to be a safe and effective surgical technique for non-penetrating glaucoma surgery that yields the opportunity of a sufficient IOP reduction for eyes unsuitable for canaloplasty.
Ciller, Carlos; De Zanet, Sandro I; Rüegsegger, Michael B; Pica, Alessia; Sznitman, Raphael; Thiran, Jean-Philippe; Maeder, Philippe; Munier, Francis L; Kowal, Jens H; Cuadra, Meritxell Bach
2015-07-15
Proper delineation of ocular anatomy in 3-dimensional (3D) imaging is a big challenge, particularly when developing treatment plans for ocular diseases. Magnetic resonance imaging (MRI) is presently used in clinical practice for diagnosis confirmation and treatment planning for treatment of retinoblastoma in infants, where it serves as a source of information, complementary to the fundus or ultrasonographic imaging. Here we present a framework to fully automatically segment the eye anatomy for MRI based on 3D active shape models (ASM), and we validate the results and present a proof of concept to automatically segment pathological eyes. Manual and automatic segmentation were performed in 24 images of healthy children's eyes (3.29 ± 2.15 years of age). Imaging was performed using a 3-T MRI scanner. The ASM consists of the lens, the vitreous humor, the sclera, and the cornea. The model was fitted by first automatically detecting the position of the eye center, the lens, and the optic nerve, and then aligning the model and fitting it to the patient. We validated our segmentation method by using a leave-one-out cross-validation. The segmentation results were evaluated by measuring the overlap, using the Dice similarity coefficient (DSC) and the mean distance error. We obtained a DSC of 94.90 ± 2.12% for the sclera and the cornea, 94.72 ± 1.89% for the vitreous humor, and 85.16 ± 4.91% for the lens. The mean distance error was 0.26 ± 0.09 mm. The entire process took 14 seconds on average per eye. We provide a reliable and accurate tool that enables clinicians to automatically segment the sclera, the cornea, the vitreous humor, and the lens, using MRI. We additionally present a proof of concept for fully automatically segmenting eye pathology. This tool reduces the time needed for eye shape delineation and thus can help clinicians when planning eye treatment and confirming the extent of the tumor. Copyright © 2015 Elsevier Inc. All rights reserved.
Karimi, Alireza; Razaghi, Reza; Biglari, Hasan; Sabbaghi, Hamideh; Sera, Toshihiro; Kudo, Susumu
2018-04-20
This study was aimed at investigating the role of IVI angle on the induced stresses and deformations among the components of the eye. Thereafter, the most optimal angle of IVI to minimize the complications of post IVI at the injection site on a basis of the computed stresses via a Fluid-Structure Interaction (FSI) computational model was proposed. IntraVitreal Injection (IVI) is broadly employed as a principal treatment of vascular vitro-retinal diseases. So far, there have been reports regarding the complications of post IVI and determine them as severe uveitis, tractional retinal detachment, IntraOcular Pressure (IOP) elevation as well as ocular haemorrhage. However, there is a lack of knowledge on how to reduce the subsequent ocular tissue damage and patient symptoms in the injection site. Seven different IVI angles were simulated, including 0∘, 15∘, 30∘, 45∘, 60∘, 75∘, and 90∘, through the Finite Element (FE) code; and the term, 'post IVI complication' or 'injury', in the results was interpreted as the level of maximal principal stress in the eye components. The results revealed the lowest amount of stresses at the angle of 45∘ in respect to the horizontal line (acute to the surface of the sclera) for the lens, iris, vitreous body, aqueous body, ciliary body, sclera, retina, and choroid. The cornea illustrated the same amount of stress at the angles of 45∘, 60∘, 75∘, and 90∘ with the highest one at the IVI angle of 30∘. The lowest and the highest stresses among the eye components regardless of IVI angle were observed in the choroid and retina/sclera, respectively, which imply the importance of the IVI angle on the stresses of these eye components. The findings of the contemporary research revealed that the IVI angle of 45∘ would trigger less post IVI complications and, as a result, a more effective surgery outcome compared to the other angles, i.e., 0∘, 15∘, 30∘, 60∘, 75∘, and 90∘.
Effect of hypokinesia on blood microcirculation
NASA Technical Reports Server (NTRS)
Chernukh, A. M.; Gazenko, O. G.; Fedorov, B. M.; Krupina, T. N.; Aleksandrov, P. N.; Shagal, D. I.; Ranferova, N. Y.; Proskurina, T. N.
1980-01-01
Blood microcirculation in the region of the scleral bulbar conjunctiva and the nail folds on the fingers and toes was studied in 18 practically healthy men during 182 day antiorthostatic hypokinesia and 30 day rehabilitation period. Marked changes in microcirculation in the sclera and feet and less evident changes on the hands was revealed. A complex of special prophylactic physical exercises had a distinctly favorable effect on circulation in the hands.
Parys-van Ginderdeuren, R; van den Oord, J J; Missotten, L
1997-01-01
Three patients with a choroidal melanoma, treated with HDR (High Dose Rate) Strontium-90 brachytherapy, underwent an enucleation. Radiation effect was only visible at the irradiation zone with a brisk transition to normal tissue. Tumour was replaced by necrotic and scar tissue. The underlying sclera had a markedly reduced number of fibrocytes, but no structural alteration of the collagen stroma.
Increased Expression of CCN2 in the Red Flashing Light-Induced Myopia in Guinea Pigs
Wang, Hong; Zhuang, Kang; Gao, Lei; Zhang, Linna; Yang, Hongling
2013-01-01
Visual environment plays an important role in the occurrence of myopia. We previously showed that the different flashing lights could result in distinct effects on the ocular growth and development of myopia. CCN2 has been reported to regulate various cellular functions and biological processes. However, whether CCN2 signaling was involved in the red flashing light-induced myopia still remains unknown. In the present study, we investigated the effects of the red flashing lights exposure on the refraction and axial length of the eyes in vivo and then evaluated their effects on the expression of CCN2 and TGF-β in sclera tissues. Our data showed that the eyes exposed to the red flashing light became more myopic with a significant increase of the axial length and decrease of the refraction. Both CCN2 and TGF-β, as well as p38 MAPK and PI3K, were highly expressed in the sclera tissues exposed to the red flashing light. Both CCN2 and TGF-β were found to have the same gene expression profile in vivo. In conclusion, our findings found that CCN2 signaling pathway plays an important role in the red flashing light-induced myopia in vivo. Moreover, our study establishes a useful animal model for experimental myopia research. PMID:23936844
Chapman, G B; Tarboush, R; Eagles, D A; Connaughton, V P
2009-08-01
The distribution and ultrastructural features of peripheral nerve processes in the extra-retinal layers of the eyes of the zebrafish, Danio rerio (Hamilton), were investigated using light and transmission electron microscopy. A comparative study of the quality of preservation provided by three different fixation procedures revealed no consistently striking general differences. However, somewhat subjectively, the fixative containing Millonig's buffer did consistently provide better fixation of myelin. Overall, nerve processes, depending on the site studied, were distributed as either (1) bundles (in the choroid near the optic nerve head and in the choroid adjacent to the limbus), (2) linear arrays (in the junction between the sclera and cartilage and in the choroid adjacent to the retina) or (3) individual units (in the choroid under the cartilage or in the sclera). Both myelinated and unmyelinated processes were identified in these locations. Myelinated processes usually contained both neurofilaments and neurotubules, but a few apparently contained only neurofilaments. Unmyelinated processes usually contained mainly neurotubules, but a few apparently contained only neurofilaments. Taken together, these findings indicate innervation of extra-retinal structures, as seen in zebrafish, is highly conserved among vertebrates, further supporting the use of zebrafish as a model for the vertebrate visual system.
Eye contrast polarity is critical for face recognition by infants.
Otsuka, Yumiko; Motoyoshi, Isamu; Hill, Harold C; Kobayashi, Megumi; Kanazawa, So; Yamaguchi, Masami K
2013-07-01
Just as faces share the same basic arrangement of features, with two eyes above a nose above a mouth, human eyes all share the same basic contrast polarity relations, with a sclera lighter than an iris and a pupil, and this is unique among primates. The current study examined whether this bright-dark relationship of sclera to iris plays a critical role in face recognition from early in development. Specifically, we tested face discrimination in 7- and 8-month-old infants while independently manipulating the contrast polarity of the eye region and of the rest of the face. This gave four face contrast polarity conditions: fully positive condition, fully negative condition, positive face with negated eyes ("negative eyes") condition, and negated face with positive eyes ("positive eyes") condition. In a familiarization and novelty preference procedure, we found that 7- and 8-month-olds could discriminate between faces only when the contrast polarity of the eyes was preserved (positive) and that this did not depend on the contrast polarity of the rest of the face. This demonstrates the critical role of eye contrast polarity for face recognition in 7- and 8-month-olds and is consistent with previous findings for adults. Copyright © 2013 Elsevier Inc. All rights reserved.
Analysis of eye health in the Thai population.
Yospaiboon, Yosanan; Yospaiboon, Kasem; Ratanapakorn, Tanapat; Sinawat, Suthasinee; Sanguansak, Thuss; Bhoomibunchoo, Chavakij
2012-07-01
To assess national eye health as a baseline for improving medical education, services and research. Information on eye illness among out- and in-patients was based on hospital claims from the three national health insurance schemes in 2010. The data were analyzed by age groups. In 2010, 4,982,025 out-patient visits and 187,080 in-patient admissions were reported. The five most common outpatient eye conditions were disorders of the (1) conjunctiva (H10-H13) (2) eyelid, lacrimal system and orbit (H00-H06) (3) lens (H25-28) (4) sclera, cornea, iris and ciliary body (H15-H22) and (5) glaucoma (H40-H42). The five most common inpatient eye diseases were (1) disorders of lens (H25-H28) (2) conjunctiva (H10-H13) (3) sclera, cornea, iris and ciliary body (H15-H22) (4) choroid and retina (H30-H35) and (5) glaucoma (H40-H42). Information on the most frequent eye diseases-including the types and frequency of high risk conditions, the diseases causing the most impact on vision and resulting in the highest health expenditures-will be used to (a) revise the curricula for medical education (b) to improve eye care services and (c) to improve access to data for research themes tailored to local and national needs.
An Operational Evaluation of Extended-Wear Soft Contact Lenses in an Armored Division.
1987-08-01
has been demonstrated in the tarsal portion of the palpebral conjunctiva , usually of the upper . lid (Korb et al., 1983). Termed giant papillary...segment of the eye; any disease that affected the cornea, conjunctiva or sclera; corneal hypoesthesia; low tear breakup time or insufficient...evaluation of the following: lids, conjunctiva , limbus, cornea, anterior chamber, and tarsal plate. . 14 v\\Md rn, , !,F~l *O NO .. W,% Quantification of
1978-10-17
characteristics for optical second- harmonic generation. The collage component of conective tissue may be the principal site for the observed harmonic...Generation in Tissue ; Second Harmonic Generation in Collage; Glutathione, 5MB; Mechanisms; Conversion Efficiency; Significance of order UL AIM UY#m~wmev...sclera, and skin on 694 im. Q-switched ruby laser irradiation. A possible source of this second-harmonic generation was tissue collagen; because of
Penha, Alexandra Marcha; Schaeffel, Frank; Feldkaemper, Marita
2011-01-01
Insulin stimulates eye growth in chicks and this effect is greatly enhanced if the retinal image is degraded by the defocus of either sign. However, it is unclear whether the insulin receptor (IR) is expressed at all in the chicken retina in animals 1-2 weeks post-hatching. We have investigated IR expression and whether IR transcript abundance varies in the fundal layers. To elucidate the possible role of insulin and insulin-like growth factor (IGF)-1 signaling in eye growth regulation, mRNA (mRNA) levels were measured for insulin, IGF-1, IR, and IGF-1 receptor (IGF-1R) during imposed negative or positive defocus. Chicks were treated binocularly with positive or negative spectacle lenses for 4 or 24 h, or they remained untreated (n=6, for each treatment group). Northern blot analyses were performed to screen for transcription variants in the different fundal layers of untreated animals. Real-time PCR was used to quantify IR, IGF-1R, IGF-1, and insulin mRNA levels in the different fundal layers of the chick eye in the three treatment groups. IR mRNA was found in all the studied tissues, although there is evidence of tissue-specific transcript variations. Three major transcripts were detected for IR. The brain, retina, and choroid showed the longest transcript (4.3 kb), which was not present in the liver. Nevertheless, the liver and brain showed a second transcript (2.6 kb) not present in the retina and choroid. A short transcript (1.3 kb) was the predominant form in the liver and choroid, and it seems to be present in the retinal pigment epithelium (RPE) and sclera as well. In the retina, no significant gene expression changes were found when defocus was imposed. Interestingly, in the RPE, both IR and IGF-1R were already downregulated after short periods (4 h) of positive lens wear. In contrast, IR and IGF-1R were upregulated in the choroid and fibrous sclera during treatment with negative, but not positive, lenses. Differences observed in the IR transcript length in different tissues suggest possibly different functions. The differential regulation of IR and IGF-1R in the RPE, choroid, and fibrous sclera is consistent with their involvement in a signaling cascade for emmetropization.
Spectral and time-resolved studies on ocular structures
NASA Astrophysics Data System (ADS)
Schweitzer, D.; Jentsch, S.; Schenke, S.; Hammer, M.; Biskup, C.; Gaillard, E.
2007-07-01
Measurements of endogeous fluorophores open the possibility for evaluation of metabolic state at the eye. For interpretation of 2-dimensional measurements of time-resolved auto fluorescence in 2 separate spectral ranges at the human eye, comparing measurements were performed on porcine eyes. Determining excitation and emission spectra, attention was drawn of proof of coenzymes NADH and FAD in isolated anatomical structures cornea, aqueous humor, lens, vitreous, neuronal retina, retinal pigment epithelium (RPE), choroid, and sclera. All these structures exhibit auto fluorescence, highest in lens. Excitation at 350 nm results in local fluorescence maxima at 460 nm, corresponding to NADH, in all structures. This short-wave excitation allows metabolic studies only at the anterior eye, because of the limited transmission of the ocular media. During excitation at 446 nm the existence of FAD is expressed by local fluorescence maxima at 530 nm. The composition fluorescence spectra allow no discrimination between single ocular structures. Approximating the dynamic fluorescence by a double exponential function, the shortest lifetimes were detected in RPE and neuronal retina. The histograms of mean lifetime t M cover each other on lens with cornea and also on sclera with choroid. Despite the lifetimes are close between RPE and neuronal retina, the relative contributions Q I are wide different. The gradient of trend lines in cluster diagrams of amplitudes α II vs. α I allows a discrimination of ocular structures.
Telocytes and stem cells in limbus and uvea of mouse eye
Luesma, María José; Gherghiceanu, Mihaela; Popescu, Laurenţiu M
2013-01-01
The potential of stem cell (SC) therapies for eye diseases is well-recognized. However, the results remain only encouraging as little is known about the mechanisms responsible for eye renewal, regeneration and/or repair. Therefore, it is critical to gain knowledge about the specific tissue environment (niches) where the stem/progenitor cells reside in eye. A new type of interstitial cell–telocyte (TC) (http://www.telocytes.com) was recently identified by electron microscopy (EM). TCs have very long (tens of micrometres) and thin (below 200 nm) prolongations named telopodes (Tp) that form heterocellular networks in which SCs are embedded. We found TCs by EM and electron tomography in sclera, limbus and uvea of the mouse eye. Furthermore, EM showed that SCs were present in the anterior layer of the iris and limbus. Adhaerens and gap junctions were found to connect TCs within a network in uvea and sclera. Nanocontacts (electron-dense structures) were observed between TCs and other cells: SCs, melanocytes, nerve endings and macrophages. These intercellular ‘feet’ bridged the intercellular clefts (about 10 nm wide). Moreover, exosomes (extracellular vesicles with a diameter up to 100 nm) were delivered by TCs to other cells of the iris stroma. The ultrastructural nanocontacts of TCs with SCs and the TCs paracrine influence via exosomes in the epithelial and stromal SC niches suggest an important participation of TCs in eye regeneration. PMID:23991685
Pharmacokinetics of pirfenidone after topical administration in rabbit eye
Sun, Guoying; Lin, Xianchai; Zhong, Hua; Yang, Yangfan; Qiu, Xuan; Ye, Chengtian; Wu, Kaili
2011-01-01
Purpose Pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone) is a new, broad-spectrum agent that has an inhibition effect on the proliferation, migration, and collagen contraction of human Tenon’s fibroblasts, and thus modulating the wound healing process of glaucoma filtering surgical site. This study investigated the pharmacokinetics of topically administered pirfenidone (0.5%) in rabbit eyes. Methods Pirfenidone solution (50 μl) was instilled into the rabbit’s conjunctival sac. The rabbits were quickly sacrificed at 2, 5, 8, 10, 15, 20, 30, 60, 90, and 120 min after the administration and ocular tissues were obtained. The concentrations of pirfenidone in conjunctiva, sclera, cornea, aqueous humor, and vitreous were determined by high performance liquid chromatography. Results After topical administration, there was wide distribution and fast clearance of pirfenidone among the various ocular tissues. The mean maximum concentrations (Cmax) of pirfenidone in cornea, conjunctiva, sclera, aqueous humor, and vitreous were 9.64 mg/g, 9.62 mg/g, 2.13 mg/g, 34.88 mg/l and 0.52 mg/l, respectively. The half-life for these tissues was 18.26, 34.16, 15.71, 70.91, and 39.48 min, respectively. Conclusions Measurable concentrations of pirfenidone are achieved in ocular tissues after topical application in rabbit model. Topical administration of pirfenidone may be an effective approach for modulation of wound healing responses in glaucoma filtration surgical site. PMID:21866212
Jia, Mingrui; Shi, Ranran; Zhao, Xuli; Fu, Zhijian; Bai, Zhijing; Sun, Tao; Zhao, Xuejun; Wang, Wenbo; Xu, Chao; Yan, Fang
2017-01-01
Abstract Mutation analysis as the gold standard is particularly important in diagnosis of osteogenesis imperfecta (OI) and it may be preventable upon early diagnosis. In this study, we aimed to analyze the clinical and genetic materials of an OI pedigree as well as to confirm the deleterious property of the mutation. A pedigree with OI was identified. All family members received careful clinical examinations and blood was drawn for genetic analyses. Genes implicated in OI were screened for mutation. The function and structure of the mutant protein were predicted using bioinformatics analysis. The proband, a 9-month fetus, showed abnormal sonographic images. Disproportionately short and triangular face with blue sclera was noticed at birth. She can barely walk and suffered multiple fractures till 2-year old. Her mother appeared small stature, frequent fractures, blue sclera, and deformity of extremities. A heterozygous missense mutation c.1009G>T (p.G337C) in the COL1A2 gene was identified in her mother and her. Bioinformatics analysis showed p.G337 was well-conserved among multiple species and the mutation probably changed the structure and damaged the function of collagen. We suggest that the mutation p.G337C in the COL1A2 gene is pathogenic for OI by affecting the protein structure and the function of collagen. PMID:28953610
Bok, Tae-Hoon; Kim, Juho; Bae, Jinho; Lee, Chong Hyun; Paeng, Dong-Guk
2014-09-24
The mechanical scanning of a single element transducer has been mostly utilized for high-frequency ultrasound imaging. However, it requires space for the mechanical motion of the transducer. In this paper, a rotational scanning ultrasound biomicroscopy (UBM) system equipped with a high-frequency angled needle transducer is designed and implemented in order to minimize the space required. It was applied to ex vivo ultrasound imaging of porcine posterior ocular tissues through a minimal incision hole of 1 mm in diameter. The retina and sclera for the one eye were visualized in the relative rotating angle range of 270°~330° and at a distance range of 6~7 mm, whereas the tissues of the other eye were observed in relative angle range of 160°~220° and at a distance range of 7.5~9 mm. The layer between retina and sclera seemed to be bent because the distance between the transducer tip and the layer was varied while the transducer was rotated. Certin features of the rotation system such as the optimal scanning angle, step angle and data length need to be improved for ensure higher accuracy and precision. Moreover, the focal length should be considered for the image quality. This implementation represents the first report of a rotational scanning UBM system.
Bok, Tae-Hoon; Kim, Juho; Bae, Jinho; Lee, Chong Hyun; Paeng, Dong-Guk
2014-01-01
The mechanical scanning of a single element transducer has been mostly utilized for high-frequency ultrasound imaging. However, it requires space for the mechanical motion of the transducer. In this paper, a rotational scanning ultrasound biomicroscopy (UBM) system equipped with a high-frequency angled needle transducer is designed and implemented in order to minimize the space required. It was applied to ex vivo ultrasound imaging of porcine posterior ocular tissues through a minimal incision hole of 1 mm in diameter. The retina and sclera for the one eye were visualized in the relative rotating angle range of 270° ∼ 330° and at a distance range of 6 ∼ 7 mm, whereas the tissues of the other eye were observed in relative angle range of 160° ∼ 220° and at a distance range of 7.5 ∼ 9 mm. The layer between retina and sclera seemed to be bent because the distance between the transducer tip and the layer was varied while the transducer was rotated. Certin features of the rotation system such as the optimal scanning angle, step angle and data length need to be improved for ensure higher accuracy and precision. Moreover, the focal length should be considered for the image quality. This implementation represents the first report of a rotational scanning UBM system. PMID:25254305
2006-07-01
retina . Our experiments have so far been limited to sheep. Our experiments have been designed to address the following questions: 1. Can ocular...We dissected sheep and cow eyes and performed fluorescence spectroscopy on all the major eye components and reports that the cornea, lens, retina ...excitation wavelengths λex = 410, 470, and 520 nm: retina ; optic nerve; outer tissue (sclera); and lens. • Contrary to the conclusions we
1995-03-30
family with autosomal dominant retinitis pigmentosa . American Journal of Human Genetics 48: 26-30. Johnston, M.C., Noden, D.M., Hazelton, R. D...create a double-layered optic cup, with the outer layer forming the retinal pigmented epithelium (RPE) and the inner layer forming the neural retina...the lens, sclera, retina and retinal pigmented epithelium (Bassas et 19 al., 1987; Zick et al., 1987; Ocrant et al., 1989; Waldbillig et al. 1990
Backache due to alkaptonuria in a middle aged man.
Arshad, Abdul Rehman; Awan, Muhammad Younus
2013-12-01
Alkaptonuria is a rare cause of backache. A 55 years old gentleman, a retired army personal had been having pain and stiffness in the spine for the last 15 years, accompanied by bluish black discolouration of face and hands. Kyphosis and reduced movement of spine were present. Other joints were spared. Osler spots were visible on the sclera. X-rays revealed calcification of intervertebral discs. Asymptomatic renal stone was identified. There was no cardiac involvement. Symptomatic care was provided.
Acute anterior uveitis as the initial presentation of alkaptonuria.
John, S S; Padhan, P; Mathews, J V; David, S
2009-01-01
Alkaptonuria is a rare autosomal recessive metabolic disorder that may present with multi-system involvement such as ochronotic arthropathy, renal, urethral and prostatic calculi, cardiac valvular lesions and pigmentation of the skin, sclera, cartilage and other connective tissues. An association of the disease with uveitis has never been reported. We report the first case of alkaptonuria with ochronotic arthropathy presenting with recurrent acute anterior uveitis as the initial manifestation. The possible common link with the HLA-B27 gene is discussed.
A novel iris localization algorithm using correlation filtering
NASA Astrophysics Data System (ADS)
Pohit, Mausumi; Sharma, Jitu
2015-06-01
Fast and efficient segmentation of iris from the eye images is a primary requirement for robust database independent iris recognition. In this paper we have presented a new algorithm for computing the inner and outer boundaries of the iris and locating the pupil centre. Pupil-iris boundary computation is based on correlation filtering approach, whereas iris-sclera boundary is determined through one dimensional intensity mapping. The proposed approach is computationally less extensive when compared with the existing algorithms like Hough transform.
Experimental scleral cross-linking increases glaucoma damage in a mouse model
Kimball, Elizabeth C.; Nguyen, Cathy; Steinhart, Matthew R.; Nguyen, Thao D.; Pease, Mary E.; Oglesby, Ericka N.; Oveson, Brian C.; Quigley, Harry A.
2014-01-01
The purpose of this study was to assess the effect of a scleral cross-linking agent on susceptibility to glaucoma damage in a mouse model. CD1 mice underwent 3 subconjunctival injections of 0.5 M glyceraldehyde (GA) in 1 week, then had elevated intraocular pressure (IOP) induced by bead injection. Degree of cross-linking was measured by enzyme-linked immunosorbent assay (ELISA), scleral permeability was measured by fluorescence recovery after photobleaching (FRAP), and the mechanical effects of GA exposure were measured by inflation testing. Control mice had buffer injection or no injection in 2 separate glaucoma experiments. IOP was monitored by Tonolab and retinal ganglion cell (RGC) loss was measured by histological axon counting. To rule out undesirable effects of GA, we performed electroretinography and detailed histology of the retina. GA exposure had no detectable effects on RGC number, retinal structure or function either histologically or electrophysiologically. GA increased cross-linking of sclera by 37% in an ELISA assay, decreased scleral permeability (FRAP, p = 0.001), and produced a steeper pressure—strain behavior by in vitro inflation testing. In two experimental glaucoma experiments, GA-treated eyes had greater RGC axon loss from elevated IOP than either buffer-injected or control eyes, controlling for level of IOP exposure over time (p = 0.01, and 0.049, multivariable regression analyses). This is the first report that experimental alteration of the sclera, by cross-linking, increases susceptibility to RGC damage in mice. PMID:25285424
Peripapillary Pachychoroid in Nonarteritic Anterior Ischemic Optic Neuropathy
Nagia, Lina; Huisingh, Carrie; Johnstone, John; Kline, Lanning B.; Clark, Mark; Girard, Michael J. A.; Mari, Jean Martial; Girkin, Christopher A.
2016-01-01
Purpose This study examined the peripapillary choroidal thickness (PCT) in nonarteritic ischemic optic neuropathy (NAION) in comparison to contralateral eyes and normal eyes. Methods We used enhanced depth imaging spectral-domain optical coherence tomography to image the optic nerve head of 20 NAION, 10 contralateral eyes, and 102 normal eyes. Following compensation, the scans were manually delineated to identify relevant surfaces including Bruch's membrane opening (BMO), Bruch's membrane, and anterior sclera. The PCT was defined as the measurement between Bruch's membrane and the anterior sclera and was measured at increasing distance from BMO. Models adjusted for age, BMO area, and axial length were used to compare the mean PCT between NAION and normal eyes, and contralateral eyes and normal eyes. Paired t-tests were used to compare the PCT between NAION and contralateral eyes. Results The mean PCT was thicker in NAION and contralateral eyes when compared with normal eyes at all distances from BMO (P < 0.001). The PCT was not significantly thicker in contralateral eyes when compared with affected NAION eyes. Choroidal thickness was thinnest in the inferior quadrant in all eyes regardless of the group. Conclusions Increased peripapillary choroidal thickness was noted in both NAION and contralateral eyes. The thicker choroid may be an associated feature or a result of the disorder. Although further longitudinal study is required to determine causation, these findings may suggest that a thickened peripapillary choroid may be a component of the disk-at-risk clinical phenotype. PMID:27583829
Anatomic features of the cetacean globe.
Miller, Sarah; Samuelson, Don; Dubielzig, Richard
2013-07-01
To provide measurements of globe dimensions and describe morphological characteristics of the cetacean globe with an emphasis on Bowman's layer and encapsulated sensory corpuscles (ESC) for available cetacean species. Cetacean globes housed at the Comparative Ocular Pathology Laboratory of Wisconsin from various odontocete and two mysticete species. Measurements were taken from formalin fixed globes and images of formalin fixed globes with embedded rulers. Histological sections of globes were used to count ESC and measure Bowman's layer. The horizontal diameter of the globe was longer than the vertical diameter. The posterior sclera was thick, causing the internal axial length (and therefore the optical axis) to be shorter than the vertical diameter. The cornea was composed of an epithelium, Bowman's layer, collagenous stroma, thin Descemet's membrane and endothelial layer. Bowman's layer was present in all specimens except one Kogia breviceps. The thickness was variable, with the acellular layer thickest in Tursiops truncatus and thinnest in Kogia sp. The iris was well vascularized and muscled while the ciliary body lacked musculature, but retained vasculature. Single and clustered ESC were found in the anterior uvea, sclera surrounding the anterior uvea, trabecular meshwork, or some combination of these locations. They were often regionally grouped and varied from 0 to 21. There were three species where no ESC were found, L. borealis, D. capensis, and S. bredanensis, but the presence of these corpuscles cannot be ruled as only one section of the globe was analyzed. © 2013 American College of Veterinary Ophthalmologists.
[Transcorneal and transscleral iontophoresis of the dexamethasone phosphate into the rabbit eye].
Raiskup-Wolf, F; Eljarrat-Binstock, E; Rehák, M; Domb, A; Frucht-Pery, J
2007-09-01
To evaluate the efficiency of the dexamethasone phosphate penetration into the rabbit eye after transcorneal and transscleral iontophoresis using a drug loaded hydrogel assembled on a portable iontophoretic Mini Ion device. lontophoresis of dexamethasone phosphate was studied in healthy rabbits using drug-loaded disposable HEMA hydrogel sponges and portable iontophoretic device. Corneal iontophoretic administration was performed with electric current of 1 mAmp for 1, 2, and 4 min. In the control group, the dexamethasone was applied in drops into the conjunctival sac. Transconjunctival and transscleral iontophoresis were performed in the pars plana area, through the conjunctiva or directly on the sclera. Dexamethasone concentrations were assayed using HPLC method. To study the anatomical changes after iontophoresis application, histological examinations of corneas excised 5 minutes and 8 hours after the procedure were performed. Dexamethasone levels in the rabbits' corneas after a single transcorneal iontophoresis were up to 38 times higher compared to those obtained after topical eye drops instillation. High drug concentrations were obtained in the retina and sclera 4 hours after transscleral iontophoresis as well. There were no statistically significant differences in the drug concentration after transscleral and tranconjunctival iontophoresis. Histological examination of the corneas after the iontophoresis showed only discrete reversible changes of the epithelium and the stroma. A short, low-current, non-invasive iontophoretic treatment using the dexamethasone-loaded hydrogels has a potential clinical value in increasing the drug's penetration into the anterior and posterior segment of the eye.
Preparation and evaluation of HPMC-based pirfenidone solution in vivo.
Yang, Mei; Yang, Yang-Fan; Lei, Ming; Ye, Cheng-Tian; Zhao, Chun-Shun; Xu, Jian-Gang; Wu, Kai-Li; Yu, Min-Bin
2017-01-01
Pirfenidone (PFD) has exhibited therapeutic potential in the treatment of cell proliferative disorders. The previously developed 0.5% water-based PFD eye drops by our team exhibited antiscarring effectiveness and ocular safety but with a limit of short half-life and poor bioavailability. To increase bioavailability of the water-based PFD eye drops, we prepared a viscous solution by adding hydroxypropyl methylcellulose (HPMC, F4M), which acted as a viscosity-enhancer. Subsequently, we compared the HPMC-based PFD solution with the water-based PFD eye drops. PFD solution with 1% HPMC (w/v) was prepared, and the viscosities at different shear rates were measured to investigate its rheology. PFD concentrations in the tear, aqueous humor, conjunctiva, cornea, and sclerae of New Zealand rabbits were detected at different time points with high-performance liquid chromatography (HPLC) following single instillation of the 0.5% PFD (w/v) water-based eye drops or HPMC-based solution. Compared with the 0.5% water-based PFD eye drops, the HPMC-based solution increased the PFD levels in tears and prolonged the residence time from 10 to more than 20 min (p < .01). Consequently, the concentrations of PFD in aqueous humor, conjunctiva, cornea, and sclera were elevated to varying degrees until 90 min after topical administration. The developed formulation possesses a same readily administration and simple preparation as the PFD eye drops; however, the HPMC-based solution exhibited the higher bioavailability.
Zaky, Khaled S; Khalifa, Yasser M
2012-01-01
Purpose: To determine the efficacy of preoperative subconjunctival injection of mitomycin C a day before surgery in the management of recurrent pterygium. Materials and Methods: Randomized comparative case series. Fifty eyes with recurrent pterygium were randomly divided into two groups; the mitomycin injection group (25 eyes) and the mitomycin application group (25 eyes). The mitomycin injection group underwent preoperative subconjunctival injection of mitomycin C in low dose (0.1 ml of 0.15 mg/ml) a day before bare sclera pterygium excision surgery. The mitomycin application group underwent bare sclera pterygium excision with topical application of mitomycin C (same concentration). Results: At one year of follow-up, 24 of 25 eyes (96%) in the mitomycin injection group and 23 of 25 (92%) eyes in the mitomycin application group were free of recurrence. The difference was statistically insignificant. As regards postoperative complications, delayed epithelization (more than two weeks) occurred in two eyes (8%) in the mitomycin injection group and in one eye (4%) in the mitomycin application group. Scleral thinning was reported in one eye (4%) in the mitomycin application group which resolved within three weeks after surgery, no other serious postoperative complications were reported. Conclusion: Preoperative subconjunctival injection of mitomycin C in low dose (0.1 ml of 0.15 mg/ml) a day before pterygium surgery is a simple and effective modality for management of recurrent pterygium. It has the advantage of low recurrence and complications’ rate. PMID:22824595
Compartmental Innervation of the Superior Oblique Muscle in Mammals.
Le, Alan; Poukens, Vadims; Ying, Howard; Rootman, Daniel; Goldberg, Robert A; Demer, Joseph L
2015-10-01
Intramuscular innervation of mammalian horizontal rectus extraocular muscles (EOMs) is compartmental. We sought evidence of similar compartmental innervation of the superior oblique (SO) muscle. Three fresh bovine orbits and one human orbit were dissected to trace continuity of SO muscle and tendon fibers to the scleral insertions. Whole orbits were also obtained from four humans (two adults, a 17-month-old child, and a 33-week stillborn fetus), two rhesus monkeys, one rabbit, and one cow. Orbits were formalin fixed, embedded whole in paraffin, serially sectioned in the coronal plane at 10-μm thickness, and stained with Masson trichrome. Extraocular muscle fibers and branches of the trochlear nerve (CN4) were traced in serial sections and reconstructed in three dimensions. In the human, the lateral SO belly is in continuity with tendon fibers inserting more posteriorly on the sclera for infraducting mechanical advantage, while the medial belly is continuous with anteriorly inserting fibers having mechanical advantage for incycloduction. Fibers in the monkey superior SO insert more posteriorly on the sclera to favor infraduction, while the inferior portion inserts more anteriorly to favor incycloduction. In all species, CN4 bifurcates prior to penetrating the SO belly. Each branch innervates a nonoverlapping compartment of EOM fibers, consisting of medial and lateral compartments in humans and monkeys, and superior and inferior compartments in cows and rabbits. The SO muscle of humans and other mammals is compartmentally innervated in a manner that could permit separate CN4 branches to selectively influence vertical versus torsional action.
High precision laser sclerostomy
NASA Astrophysics Data System (ADS)
Góra, W. S.; Urich, A.; McIntosh, L.; Carter, R. M.; Wilson, C. G.; Dhillon, B.; Hand, D. P.; Shephard, J. D.
2015-03-01
Ultrafast lasers offer a possibility of removing soft ophthalmic tissue without introducing collateral damage at the ablation site or in the surrounding tissue. The potential for using ultrashort pico- and femtosecond pulse lasers for modification of ophthalmic tissue has been reported elsewhere and has resulted in the introduction of new, minimally invasive procedures into clinical practice. Our research aims to define the most efficient parameters to allow for the modification of scleral tissue without introducing collateral damage. Our experiments were carried out on hydrated porcine sclera in vitro. Porcine sclera, which has similar collagen organization, histology and water content (~70%) to human tissue was used. Supporting this work we present a 2D finite element blow-off model which employs a one-step heating process. It is assumed that the incident laser radiation that is not reflected is absorbed in the tissue according to the Beer-Lambert law and transformed into heat energy. The experimental setup uses an industrial picosecond laser (TRUMPF TruMicro 5x50) with 5.9 ps pulses at 1030 nm, with pulse energies up to 125 μJ and a focused spot diameter of 35 μm. Use of a beam steering scan head allows flexibility in designing complicated scanning patterns. In this study we have demonstrated that picosecond pulses are capable of removing scleral tissue without introducing any major thermal damage which offers a possible route for minimally invasive sclerostomy. In assessing this we have tested several different scanning patterns including single line ablation, square and circular cavity removal.
Ultrafast laser machining of porcine sclera
NASA Astrophysics Data System (ADS)
Góra, W. S.; Carter, R. M.; Dhillon, B.; Hand, D. P.; Shephard, J. D.
2015-07-01
The use of ultrafast lasers (pulsed lasers with pulse lengths of a few picoseconds or less) offers the possibility for minimally invasive removal of soft ophthalmic tissue. The potential for using pico- and femtosecond pulses for modification of scleral tissue has been reported elsewhere [1-6] and has resulted in the introduction of new, minimally invasive, procedures into clinical practice [3, 5-10]. Our research is focused on finding optimal parameters for picosecond laser machining of scleral tissue without introducing any unwanted collateral damage to the tissue. Experiments were carried out on hydrated porcine sclera in vitro, which has similar collagen organization, histology and water content (~70%) to human tissue. In this paper we present a 2D finite element ablation model which employs a one-step heating process. It is assumed that the incident laser radiation that is not reflected is absorbed in the tissue according to the Beer-Lambert law and transformed into heat energy. The experimental setup uses an industrial picosecond laser (TRUMPF TruMicro 5x50) with 5.9 ps pulses at 1030 nm, with pulse energies up to 125 μJ and a focused spot diameter of 35 μm. The use of a scan head allows flexibility in designing various scanning patterns. We show that picosecond pulses are capable of modifying scleral tissue without introducing collateral damage. This offers a possible route for minimally invasive sclerostomy. Many scanning patterns including single line ablation, square and circular cavity removal were tested.
Telocytes and stem cells in limbus and uvea of mouse eye.
Luesma, María José; Gherghiceanu, Mihaela; Popescu, Laurenţiu M
2013-08-01
The potential of stem cell (SC) therapies for eye diseases is well-recognized. However, the results remain only encouraging as little is known about the mechanisms responsible for eye renewal, regeneration and/or repair. Therefore, it is critical to gain knowledge about the specific tissue environment (niches) where the stem/progenitor cells reside in eye. A new type of interstitial cell-telocyte (TC) (www.telocytes.com) was recently identified by electron microscopy (EM). TCs have very long (tens of micrometres) and thin (below 200 nm) prolongations named telopodes (Tp) that form heterocellular networks in which SCs are embedded. We found TCs by EM and electron tomography in sclera, limbus and uvea of the mouse eye. Furthermore, EM showed that SCs were present in the anterior layer of the iris and limbus. Adhaerens and gap junctions were found to connect TCs within a network in uvea and sclera. Nanocontacts (electron-dense structures) were observed between TCs and other cells: SCs, melanocytes, nerve endings and macrophages. These intercellular 'feet' bridged the intercellular clefts (about 10 nm wide). Moreover, exosomes (extracellular vesicles with a diameter up to 100 nm) were delivered by TCs to other cells of the iris stroma. The ultrastructural nanocontacts of TCs with SCs and the TCs paracrine influence via exosomes in the epithelial and stromal SC niches suggest an important participation of TCs in eye regeneration. © 2013 The Authors. Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Ohngemach, S; Hagel, G; Schaeffel, F
1997-01-01
Previous experiments in chickens have shown that dopamine released from the retina may be one of the messengers controlling the growth of the underlying sclera. It is also possible, however, that the apparent relationship between dopamine and myopia is secondary and artifactual. We have done experiments to assess this hypothesis. Using High Pressure Liquid Chromatography with electrochemical detection (HPLC-ED), we have asked whether changes in dopamine metabolism are restricted to the local retinal regions in which myopia was locally induced. Furthermore, we have measured the concentrations of biogenic amines separately in different fundal layers (vitreous, retina, choroid, and sclera) to find out how changes induced by "deprivation" (= removal of high spatial frequencies from the retinal image by translucent eye occluders which produce "deprivation myopia") are transmitted through these layers. Finally, we have repeated the deprivation experiments after intravitreal application of the irreversible dopamine re-uptake blocker reserpine to see how suppression of dopaminergic transmission affects these changes. We found that (1) Alterations in retinal dopamine metabolism were indeed restricted to the retinal areas in which myopia was induced. (2) The retina was the major source of dopamine release with a steep gradient both to the vitreal and choroidal side. Vitreal content was about one-tenth, choroidal content about one-third, and scleral content about one-twentieth of that of the retina. (3) There was a drop by about 40% in vitreal dopamine, DOPAC (3,4-dihydroxyphenylacetic acid) and HVA (homovanilic acid) concentrations following deprivation which occurred already at a time where little changes could yet be seen in their total retinal contents. (4) Choroidal and scleral dopamine levels were not affected by deprivation, indicating that other messengers must relay the information to the sclera. (5) A single intravitreal injection of reserpine lowered dopamine and HVA levels in retina and vitreous for at least 10 days in a dose-dependent fashion and diminished or suppressed further effects of deprivation on these compounds. DOPAC levels continued to change upon deprivation even after reserpine injection (Fig. 3). Our results suggest that the release rates of dopamine from retinal amacrine cells can be estimated from vitreal dopamine concentrations; furthermore, they are in line with the hypothesis that there is an inverse relationship between dopamine release and axial eye growth rates. Although our experiments do not ultimately prove that dopamine has a functional role in the visual control of eye growth, they are in line with this notion.
Penha, Alexandra Marcha; Schaeffel, Frank
2011-01-01
Purpose Insulin stimulates eye growth in chicks and this effect is greatly enhanced if the retinal image is degraded by the defocus of either sign. However, it is unclear whether the insulin receptor (IR) is expressed at all in the chicken retina in animals 1–2 weeks post-hatching. We have investigated IR expression and whether IR transcript abundance varies in the fundal layers. To elucidate the possible role of insulin and insulin-like growth factor (IGF)-1 signaling in eye growth regulation, mRNA (mRNA) levels were measured for insulin, IGF-1, IR, and IGF-1 receptor (IGF-1R) during imposed negative or positive defocus. Methods Chicks were treated binocularly with positive or negative spectacle lenses for 4 or 24 h, or they remained untreated (n=6, for each treatment group). Northern blot analyses were performed to screen for transcription variants in the different fundal layers of untreated animals. Real-time PCR was used to quantify IR, IGF-1R, IGF-1, and insulin mRNA levels in the different fundal layers of the chick eye in the three treatment groups. Results IR mRNA was found in all the studied tissues, although there is evidence of tissue-specific transcript variations. Three major transcripts were detected for IR. The brain, retina, and choroid showed the longest transcript (4.3 kb), which was not present in the liver. Nevertheless, the liver and brain showed a second transcript (2.6 kb) not present in the retina and choroid. A short transcript (1.3 kb) was the predominant form in the liver and choroid, and it seems to be present in the retinal pigment epithelium (RPE) and sclera as well. In the retina, no significant gene expression changes were found when defocus was imposed. Interestingly, in the RPE, both IR and IGF-1R were already downregulated after short periods (4 h) of positive lens wear. In contrast, IR and IGF-1R were upregulated in the choroid and fibrous sclera during treatment with negative, but not positive, lenses. Conclusions Differences observed in the IR transcript length in different tissues suggest possibly different functions. The differential regulation of IR and IGF-1R in the RPE, choroid, and fibrous sclera is consistent with their involvement in a signaling cascade for emmetropization. PMID:21655358
Lee, Sang-Mok; Choi, Hyuk Jin; Choi, Heejin; Kim, Mee Kum; Wee, Won Ryang
2016-10-07
BACKGROUND: Though the development and fitting of scleral contact lenses are expanding steadily, there is no simple method to provide scleral metrics for scleral contact lens fitting yet. The aim of this study was to establish formulae for estimation of the axial radius of curvature (ARC) of the anterior sclera using ocular biometric parameters that can be easily obtained with conventional devices. A semi-automated stitching method and a computational analysis tool for calculating ARC were developed by using the ImageJ and MATLAB software. The ARC of all the ocular surface points were analyzed from the composite horizontal cross-sectional images of the right eyes of 24 volunteers; these measurements were obtained using anterior segment optical coherence tomography for a previous study (AS-OCT; Visante). Ocular biometric parameters were obtained from the same volunteers with slit-scanning topography and partial coherence interferometry. Correlation analysis was performed between the ARC at 8 mm to the axis line (ARC[8]) and other ocular parameters (including age). With ARC obtained on several nasal and temporal points (7.0, 7.5, 8.0, 8.5, and 9.0 mm from the axis line), univariate and multivariate linear regression analyses were performed to develop a model for estimating ARC with the help of ocular biometric parameters. Axial length, spherical equivalent, and angle kappa showed correlations with temporal ARC[8] (tARC[8]; Pearson's r = 0.653, -0.579, and -0.341; P = 0.001, 0.015, and 0.015, respectively). White-to-white corneal diameter (WTW) and anterior chamber depth (ACD) showed correlation with nasal ARC[8] (nARC[8]; Pearson's r = -0.492 and -0.461; P = 0.015 and 0.023, respectively). The formulae for estimating scleral curvatures (tARC, nARC, and average ARC) were developed as a function of axial length, ACD, WTW, and distance from the axis line, with good determinant power (72 - 80 %; SPSS ver. 22.0). Angle kappa showed strong correlation with axial length (Pearson's r = -0.813, P <0.001), and the different correlation patterns of nasal and temporal ARC with axial length can be explained by the ocular surface deviation represented by angle kappa. Axial length, ACD, and WTW are useful parameters for estimating the ARC of the anterior sclera, which is important for the haptic design of scleral contact lenses. Angle kappa affects the discrepancies between the nasal and temporal scleral curvature.
Optical coherence tomography for glucose monitoring in blood
NASA Astrophysics Data System (ADS)
Ullah, Hafeez; Hussain, Fayyaz; Ikram, Masroor
2015-08-01
In this review, we have discussed the potential application of the emerging imaging modality, i.e., optical coherence tomography (OCT) for glucose monitoring in biological tissues. OCT provides monitoring of glucose diffusion in different fibrous tissues like in sclera by determining the permeability rate with acceptable accuracy both in type 1 and in type 2 diabetes. The maximum precision of glucose measurement in Intralipid suspensions, for example, with the OCT technique yields the accuracy up to 4.4 mM for 10 % Intralipid and 2.2 mM for 3 % Intralipid.
Depth-resolved monitoring of analytes diffusion in ocular tissues
NASA Astrophysics Data System (ADS)
Larin, Kirill V.; Ghosn, Mohamad G.; Tuchin, Valery V.
2007-02-01
Optical coherence tomography (OCT) is a noninvasive imaging technique with high in-depth resolution. We employed OCT technique for monitoring and quantification of analyte and drug diffusion in cornea and sclera of rabbit eyes in vitro. Different analytes and drugs such as metronidazole, dexamethasone, ciprofloxacin, mannitol, and glucose solution were studied and whose permeability coefficients were calculated. Drug diffusion monitoring was performed as a function of time and as a function of depth. Obtained results suggest that OCT technique might be used for analyte diffusion studies in connective and epithelial tissues.
High-resolution frequency domain second harmonic optical coherence tomography
NASA Astrophysics Data System (ADS)
Su, Jianping; Tomov, I. V.; Jiang, Yi; Chen, Zhongping
2007-02-01
We used continuum generated in an 8.5 cm long fiber by a femtosecond Yb fiber laser to improve threefold the axial resolution of frequency domain SH-OCT to 12μm. The acquisition time was shortened by more than two orders of magnitude compared to time domain SH-OCT. The system was applied to image biological tissue of fish scales, pig leg tendon and rabbit eye sclera. Highly organized collagen fibrils can be visualized in the recorded images. Polarization dependence on second harmonic has been used to obtain polarization resolved images.
The iris – a window into the genetics of common and rare eye diseases
Morrison, Patrick J
2010-01-01
Visual examination, without instruments, of the eye allows inspection of the iris, sclera, cornea and, through the iris, some abnormalities of the lens and retina. Several hereditary disorders can easily be recognised by characteristic iris changes. This review discusses changes in the iris, visible lens anomalies, and changes in the cornea surrounding the iris. A genetic diagnosis can help with management of diseases. Some conditions are single gene disorders, some are chromosomal rearrangements, and some are abnormalities of fetal development. PMID:20844723
Penetrating ocular trauma from trampoline spring.
Spokes, David; Siddiqui, Salina; Vize, Colin
2010-02-01
The case is presented of a 12-year old boy who sustained severe penetrating ocular trauma while playing on a domestic trampoline. A main spring broke under tension and the hook had struck the eye at high velocity and penetrated the sclera. Primary repair was undertaken but on review it became apparent the eye could not be salvaged. Evisceration was carried out and an orbital implant was placed. Post-operative cosmesis is acceptable. This type of injury has not been reported before. Adult supervision of children on trampolines is recommended to minimise the chance of serious injury.
Kimmel, Daniel L.; Mammo, Dagem; Newsome, William T.
2012-01-01
From human perception to primate neurophysiology, monitoring eye position is critical to the study of vision, attention, oculomotor control, and behavior. Two principal techniques for the precise measurement of eye position—the long-standing sclera-embedded search coil and more recent optical tracking techniques—are in use in various laboratories, but no published study compares the performance of the two methods simultaneously in the same primates. Here we compare two popular systems—a sclera-embedded search coil from C-N-C Engineering and the EyeLink 1000 optical system from SR Research—by recording simultaneously from the same eye in the macaque monkey while the animal performed a simple oculomotor task. We found broad agreement between the two systems, particularly in positional accuracy during fixation, measurement of saccade amplitude, detection of fixational saccades, and sensitivity to subtle changes in eye position from trial to trial. Nonetheless, certain discrepancies persist, particularly elevated saccade peak velocities, post-saccadic ringing, influence of luminance change on reported position, and greater sample-to-sample variation in the optical system. Our study shows that optical performance now rivals that of the search coil, rendering optical systems appropriate for many if not most applications. This finding is consequential, especially for animal subjects, because the optical systems do not require invasive surgery for implantation and repair of search coils around the eye. Our data also allow laboratories using the optical system in human subjects to assess the strengths and limitations of the technique for their own applications. PMID:22912608
Visualization of Sliding and Deformation of Orbital Fat During Eye Rotation
Hötte, Gijsbert J.; Schaafsma, Peter J.; Botha, Charl P.; Wielopolski, Piotr A.; Simonsz, Huibert J.
2016-01-01
Purpose Little is known about the way orbital fat slides and/or deforms during eye movements. We compared two deformation algorithms from a sequence of MRI volumes to visualize this complex behavior. Methods Time-dependent deformation data were derived from motion-MRI volumes using Lucas and Kanade Optical Flow (LK3D) and nonrigid registration (B-splines) deformation algorithms. We compared how these two algorithms performed regarding sliding and deformation in three critical areas: the sclera-fat interface, how the optic nerve moves through the fat, and how the fat is squeezed out under the tendon of a relaxing rectus muscle. The efficacy was validated using identified tissue markers such as the lens and blood vessels in the fat. Results Fat immediately behind the eye followed eye rotation by approximately one-half. This was best visualized using the B-splines technique as it showed less ripping of tissue and less distortion. Orbital fat flowed around the optic nerve during eye rotation. In this case, LK3D provided better visualization as it allowed orbital fat tissue to split. The resolution was insufficient to visualize fat being squeezed out between tendon and sclera. Conclusion B-splines performs better in tracking structures such as the lens, while LK3D allows fat tissue to split as should happen as the optic nerve slides through the fat. Orbital fat follows eye rotation by one-half and flows around the optic nerve during eye rotation. Translational Relevance Visualizing orbital fat deformation and sliding offers the opportunity to accurately locate a region of cicatrization and permit an individualized surgical plan. PMID:27540495
Götzinger, Erich; Pircher, Michael; Baumann, Bernhard; Hirn, Cornelia; Vass, Clemens; Hitzenberger, Christoph K.
2010-01-01
Purpose To analyze the physical origin of atypical scanning laser polarimetry (SLP) patterns. To compare polarization-sensitive optical coherence tomography (PS-OCT) scans to SLP images. To present a method to obtain pseudo-SLP images by PS-OCT that are free of atypical artifacts. Methods Forty-one eyes of healthy subjects, subjects with suspected glaucoma, and patients with glaucoma were imaged by SLP (GDx VCC) and a prototype spectral domain PS-OCT system. The PS-OCT system acquires three-dimensional (3D) datasets of intensity, retardation, and optic axis orientation simultaneously within 3 seconds. B-scans of intensity and retardation and en face maps of retinal nerve fiber layer (RNFL) retardation were derived from the 3D PS-OCT datasets. Results were compared with those obtained by SLP. Results Twenty-two eyes showed atypical retardation patterns, and 19 eyes showed normal patterns. From the 22 atypical eyes, 15 showed atypical patterns in both imaging modalities, five were atypical only in SLP images, and two were atypical only in PS-OCT images. In most (15 of 22) atypical cases, an increased penetration of the probing beam into the birefringent sclera was identified as the source of atypical patterns. In such cases, the artifacts could be eliminated in PS-OCT images by depth segmentation and exclusion of scleral signals. Conclusions PS-OCT provides deeper insight into the contribution of different fundus layers to SLP images. Increased light penetration into the sclera can distort SLP retardation patterns of the RNFL. PMID:19036999
May, Christian Albrecht
2005-01-01
To characterize further non-vascular smooth muscle cells (NVSMC) in the choroid of the human eye, extensive morphological studies were performed including a three-dimensional distribution of NVSMC in the adult human eye and their appearance during development. Whole mounts and sections through the choroid and sclera of eyes of 42 human donors (between the 13th week of gestation and 89 years of age) were stained with antibodies against smooth muscle actin and other markers for smooth muscle cells. On the basis of their morphological localization, three groups of NVSMC could be distinguished in the adult eyes: (a) a semicircular arrangement of NVSMC in the suprachoroid and inner sclera, around the entry of posterior ciliary arteries and nerves; (b) NVSMC parallel to the vessels in the posterior eye segment between the point of entry of the posterior ciliary arteries and the point of exit of the vortex veins; and (c) a dense plaque-like arrangement of NVSMC in the suprachoroid, overlying the foveal region. The last of these groups showed most pronounced interindividual differences. During development, the first NVSMC to be observed at the 20th week of gestation belonged to group b. A complete NVSMC network was first observed in a 6-year-old donor eye. All three groups stained positive for smoothelin, caldesmon and calponin in all localizations. The NVSMC show a distinct distribution that might reflect different aspects of their function in the choroid and suprachoroid. All cells could be histochemically characterized as truly contractile. PMID:16191166
Park, Hae-Young Lopilly; Kim, Jie Hyun; Jung, Younhea; Park, Chan Kee
2017-08-01
We investigated the extracellular matrix (ECM) of the lamina cribrosa (LC) and peripapillary sclera (PPS) and compared histone acetylation and related enzymes to identify racial differences between Korean and Caucasian donor eyes. Posterior segment tissues were obtained from 30 Caucasian donors and 42 age and axial length-matched Korean donors. Histone modification was assessed for histone deacetylase (HDAC) 2, HDAC3, and acetylated histone H3. The promoter regions of the major ECM in the LC and PPS including collagen type I and III, and elastic fiber components (elastin and fibrillin-1) and lysyl oxidase enzymes including lysyl oxidase-like 1 and 2 (LOXL2) were evaluated by chromatin immunoprecipitation (ChIP) assay. Protein and mRNA expression of major ECM components were assessed using real-time polymerase chain reaction analysis, western blot analysis, and immunohistochemical staining. HDAC2 and HDAC3 expression levels were decreased and acetylated histone H3 was increased in the LC and PPS of Korean eyes than Caucasian eyes. The promoter regions of LOXL2, elastin, and fribrillin-1 genes were highly acetylated in Korean LC. Expression of LOXL2 and elastic fiber components (elastin and fibrillin-1) were significantly increased in Korean LC and PPS than Caucasians according to the real-time polymerase chain reaction, western blot analyses, and quantification of elastic fiber staining. Histone acetylation status differed in the promoter regions of the elastic fiber components and LOXL2 in the LC and PPS according to race. Further study to reveal the association with these findings to the pathogenesis of glaucoma in Korean eyes is needed.
Su, James; Iomdina, Elena; Tarutta, Elena; Ward, Brian; Song, Jie; Wildsoet, Christine F.
2008-01-01
There has been generally little attention paid to the utilization of biomaterials as an anti-myopia treatment. The purpose of this study was to investigate whether polymeric hydrogels, either implanted or injected adjacent to the outer scleral surface, slow ocular elongation. White Leghorn (gallus gallus domesticus) chicks were used at 2 weeks of age. Chicks had either (1) strip of poly(2-hydroxyethyl methacrylate) (pHEMA) implanted monocularly against the outer sclera at the posterior pole, or (2) an in situ polymerizing gel [main ingredient: poly(vinyl-pyrrolidone) (PVP)] injected monocularly at the same location. Some of the eyes injected with the polymer were fitted with a diffuser or a −10D lens. In each experiment, ocular lengths were measured at regular intervals by high frequency A-scan ultrasonography, and chicks were sacrificed for histology at staged intervals. No in vivo signs of either orbital or ocular inflammation were observed. The pHEMA implant significantly increased scleral thickness by the third week, and the implant became encapsulated with fibrous tissue. The PVP-injected eyes left otherwise untreated, showed a significant increase in scleral thickness, due to increased chondrocyte proliferation and extracellular matrix deposition. However, there was no effect of the PVP injection on ocular elongation. In eyes wearing optical devices, there was no effect on either scleral thickness or ocular elongation. These results represent “proof of principle” that scleral growth can be manipulated without adverse inflammatory responses. However, since neither approach slowed ocular elongation, additional factors must influence scleral surface area expansion in the avian eye. PMID:19109950
Racioethnic Differences in Human Posterior Scleral and Optic Nerve Stump Deformation
Tamimi, Ehab A.; Pyne, Jeffrey D.; Muli, Dominic K.; Axman, Katelyn F.; Howerton, Stephen J.; Davis, Matthew R.; Girkin, Christopher A.; Vande Geest, Jonathan P.
2017-01-01
Purpose The purpose of this study was to quantify the biomechanical response of human posterior ocular tissues from donors of various racioethnic groups to better understand how differences in these properties may play a role in the racioethnic health disparities known to exist in glaucoma. Methods Sequential digital image correlation (S-DIC) was used to measure the pressure-induced surface deformations of 23 normal human posterior poles from three racioethnic groups: African descent (AD), European descent (ED), and Hispanic ethnicity (HIS). Regional in-plane principal strains were compared across three zones: the optic nerve stump (ONS), the peripapillary (PP) sclera, and non-PP sclera. Results The PP scleral tensile strains were found to be lower for ED eyes compared with AD and HIS eyes at 15 mm Hg (P = 0.024 and 0.039, respectively). The mean compressive strains were significantly higher for AD eyes compared with ED eyes at 15 mm Hg (P = 0.018). We also found that the relationship between tensile strain and pressure was significant for those of ED and HIS eyes (P < 0.001 and P = 0.004, respectively), whereas it was not significant for those of AD (P = 0.392). Conclusions Our results suggest that, assuming glaucomatous nerve loss is caused by mechanical strains in the vicinity of the optic nerve head, the mechanism of increased glaucoma prevalence may be different in those of AD versus HIS. Our ONS strain analysis also suggested that it may be important to account for ONS geometry and material properties in future scleral biomechanical analysis. PMID:28846773
High performance 3-coil wireless power transfer system for the 512-electrode epiretinal prosthesis.
Zhao, Yu; Nandra, Mandheerej; Yu, Chia-Chen; Tai, Yu-chong
2012-01-01
The next-generation retinal prostheses feature high image resolution and chronic implantation. These features demand the delivery of power as high as 100 mW to be wireless and efficient. A common solution is the 2-coil inductive power link, used by current retinal prostheses. This power link tends to include a larger-size extraocular receiver coil coupled to the external transmitter coil, and the receiver coil is connected to the intraocular electrodes through a trans-sclera trans-choroid cable. In the long-term implantation of the device, the cable may cause hypotony (low intraocular pressure) and infection. However, when a 2-coil system is constructed from a small-size intraocular receiver coil, the efficiency drops drastically which may induce over heat dissipation and electromagnetic field exposure. Our previous 2-coil system achieved only 7% power transfer. This paper presents a fully intraocular and highly efficient wireless power transfer system, by introducing another inductive coupling link to bypass the trans-sclera trans-choroid cable. With the specific equivalent load of our customized 512-electrode stimulator, the current 3-coil inductive link was measured to have the overall power transfer efficiency around 36%, with 1-inch separation in saline. The high efficiency will favorably reduce the heat dissipation and electromagnetic field exposure to surrounding human tissues. The effect of the eyeball rotation on the power transfer efficiency was investigated as well. The efficiency can still maintain 14.7% with left and right deflection of 30 degree during normal use. The surgical procedure for the coils' implantation into the porcine eye was also demonstrated.
Optically inspired biomechanical model of the human eyeball.
Sródka, Wieslaw; Iskander, D Robert
2008-01-01
Currently available biomechanical models of the human eyeball focus mainly on the geometries and material properties of its components while little attention has been given to its optics--the eye's primary function. We postulate that in the evolution process, the mechanical structure of the eyeball has been influenced by its optical functions. We develop a numerical finite element analysis-based model in which the eyeball geometry and its material properties are linked to the optical functions of the eye. This is achieved by controlling in the model all essential optical functions while still choosing material properties from a range of clinically available data. In particular, it is assumed that in a certain range of intraocular pressures, the eye is able to maintain focus. This so-called property of optical self-adjustments provides a more constrained set of numerical solutions in which the number of free model parameters significantly decreases, leading to models that are more robust. Further, we investigate two specific cases of a model that satisfies optical self-adjustment: (1) a full model in which the cornea is flexibly attached to sclera at the limbus, and (2) a fixed cornea model in which the cornea is not allowed to move at the limbus. We conclude that for a biomechanical model of the eyeball to mimic the optical function of a real eye, it is crucial that the cornea is allowed to move at the limbal junction, that the materials used for the cornea and sclera are strongly nonlinear, and that their moduli of elasticity remain in a very close relationship.
Optical clearing of the eye using the See Deep Brain technique.
Hohberger, B; Baumgart, C; Bergua, A
2017-10-01
PurposeTissue clearing has been used in anatomy for the first time in Germany over a century ago. Neuronal tissue, like cortex, was investigated in mice using a water-based optical clearing method termed See Deep Brain (SeeDB). However, although the eye belongs to the central nervous system, this histological technique was not applied in the eye up to date. We applied SeeDB for the visualization of intraocular structures.Patients and methodsFour eyes of cornea donors (two male, two female: 73-84 years) obtained from the Cornea Bank of the Department of Ophthalmology Erlangen, four chicken eyes and two mices' optic nerve were used. Bulbi were fixed in 4% paraformaldehyde in phosphate-buffered saline and treated with increasing concentrations of aqueous fructose solution with 0.5% α-thioglycerol. After SeeDB, transscleral macrophotographs of the choroid were performed.ResultsComplete transparency of the sclera was obtained in enucleated human and chicken eyes after SeeDB treatment. Macroscopical anatomy of the choroid (partially transparent due to the remaining retinal pigment epithelium and melanocytes) showing vessels and other related structures was possible without preparing slides. Mice optic nerves were also transparent after SeeDB treatment.ConclusionThe SeeDB method allows visualization of intraocular structures through a completely translucent sclera. This innovative processing technique could facilitate comprehensive qualitative and quantitative topographical anatomical studies of human and animal eyes, preserving their 3D architecture. Supra- and intrachoroidal ganglionic plexus could potentially be visualized transsclerally. Finally, clinical-pathological correlations of intraocular diseases-for example, retinal tumors-will be possible in non-dissected eyes.
Physiological characterization of ocular melanosis-affected canine melanocytes.
Dawson-Baglien, Ethan M; Noland, Erica L; Sledge, Dodd G; Kiupel, Matti; Petersen-Jones, Simon M
2018-04-27
Cairn terriers with ocular melanosis (OM) accumulate large, heavily pigmented melanocytes in the anterior uvea. Darkly pigmented plaques develop within the sclera, leading us to hypothesize that OM uveal melanocytes may have an abnormal migratory capacity. Globes from OM-affected Cairn terriers and unaffected control eyes enucleated for reasons unrelated to this study were used for immunohistochemistry and to culture melanocytes for in vitro cell behavior assays. The scleral plaques of six dogs were immunolabeled for HMB-45, MelanA, PNL2, CD18, CD204, and Iba-1 and compared with the pigment cells accumulated within the irides. Cultured uveal melanocytes from OM-affected and control dogs were compared using conventional assays measuring cell proliferation, invasion capability, and melanin production. Melanocytes isolated from OM eyes had significantly elevated levels of per-cell melanin content and production compared to controls. The majority of pigmented cells in the scleral plaques were HMB45 positive indicating a melanocytic origin. Many were also CD18 positive. No differences were observed between cultured melanocytes from OM-affected and control uvea for standard in vitro proliferation or invasion assays. Pigmented cells which accumulate in the sclera of OM-affected Cairn terriers are predominantly melanocytes; however, in vitro assays of uveal melanocytes did not reveal differences in migratory behavior between OM and control cells. Migratory behavior of OM-melanocytes may be environment-dependent. We suggest that RNA sequencing and differential expression analysis would be a useful next step in understanding this disease. © 2018 American College of Veterinary Ophthalmologists.
Ocular stem cells: a status update!
2014-01-01
Stem cells are unspecialized cells that have been a major focus of the field of regenerative medicine, opening new frontiers and regarded as the future of medicine. The ophthalmology branch of the medical sciences was the first to directly benefit from stem cells for regenerative treatment. The success stories of regenerative medicine in ophthalmology can be attributed to its accessibility, ease of follow-up and the eye being an immune-privileged organ. Cell-based therapies using stem cells from the ciliary body, iris and sclera are still in animal experimental stages but show potential for replacing degenerated photoreceptors. Limbal, corneal and conjunctival stem cells are still limited for use only for surface reconstruction, although they might have potential beyond this. Iris pigment epithelial, ciliary body epithelial and choroidal epithelial stem cells in laboratory studies have shown some promise for retinal or neural tissue replacement. Trabecular meshwork, orbital and sclera stem cells have properties identical to cells of mesenchymal origin but their potential has yet to be experimentally determined and validated. Retinal and retinal pigment epithelium stem cells remain the most sought out stem cells for curing retinal degenerative disorders, although treatments using them have resulted in variable outcomes. The functional aspects of the therapeutic application of lenticular stem cells are not known and need further attention. Recently, embryonic stem cell-derived retinal pigment epithelium has been used for treating patients with Stargardts disease and age-related macular degeneration. Overall, the different stem cells residing in different components of the eye have shown some success in clinical and animal studies in the field of regenerative medicine. PMID:25158127
High-resolution polarization sensitive OCT for ocular imaging in rodents
NASA Astrophysics Data System (ADS)
Fialová, Stanislava; Rauscher, Sabine; Gröger, Marion; Pircher, Michael; Hitzenberger, Christoph K.; Baumann, Bernhard
2015-03-01
A new high-resolution polarization sensitive optical coherence tomography system was developed for imaging rodent retina. Various light-tissue interactions such as birefringence and depolarization can change the polarization state of light. In the eye, there are several tissues that have these properties, for example retinal pigment epithelium (depolarization) and sclera (birefringence). These layers play key roles in diseases like age-related macular degeneration or glaucoma. Animal models are an important component for understanding disease pathogenesis. The gold standard for the evaluation of preclinical experiments is histology, which is an invasive and terminal procedure. Since OCT is non-invasive, it has the potential to be an alternative to histology with the benefit of long-term study of the disease progression in the same animal. In this study, a superluminescent diode with spectrum width 100 nm and mean wavelength 840 nm is used as a light source in order to enable high axial resolution. Spectrometers are custom built to enable high imaging speed that allows acquiring 3D data sets with 1024x200x1536 voxels in 3.44 s. From the acquired data, images displaying phase retardation induced by birefringence and orientation of birefringent axis were calculated. In first measurements, we were able to identify the RPE-choroid complex (depolarization effect) and the sclera (strong birefringence) in the retina of Long-Evans and Sprague-Dawley rats. Our preliminary results demonstrate the feasibility of the system for high speed/resolution imaging of the rodent retina. This is useful for longitudinal studies of disease models of retinal disease in rats and mice
Wound construction in manual small incision cataract surgery
Haldipurkar, S S; Shikari, Hasanain T; Gokhale, Vishwanath
2009-01-01
The basis of manual small incision cataract surgery is the tunnel construction for entry to the anterior chamber. The parameters important for the structural integrity of the tunnel are the self-sealing property of the tunnel, the location of the wound on the sclera with respect to the limbus, and the shape of the wound. Cataract surgery has gone beyond just being a means to get the lens out of the eye. Postoperative astigmatism plays an important role in the evaluation of final outcome of surgery. Astigmatic consideration, hence, forms an integral part of incisional considerations prior to surgery. PMID:19075401
Noninvasive spectroscopic diagnosis of superficial ocular lesions and corneal infections
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mourant, J.R.; Bigio, I.J.; Johnson, T.
The potential of a rapid noninvasive diagnostic system to detect tissue abnormalities on the surface of the eye has been investigated. The optical scatter signal from lesions and normal areas on the conjunctival sclera of the human eye were measured in vivo. It is possible to distinguish nonpigmented pingueculas from other lesions. The ability of the system to detect malignancies could not be tested because none of the measured and biopsied lesions were malignant. Optical scatter and fluorescence spectra of bacterial and fungal suspensions, and corneal irritations were also collected. Both scattering and fluorescence show potential for diagnosing corneal infections.
High-resolution frequency-domain second-harmonic optical coherence tomography
NASA Astrophysics Data System (ADS)
Su, Jianping; Tomov, Ivan V.; Jiang, Yi; Chen, Zhongping
2007-04-01
We used continuum generated in an 8.5 cm long fiber by a femtosecond Yb fiber laser to improve threefold the axial resolution of frequency domain second-harmonic optical coherence tomography (SH-OCT) to 12 μm. The acquisition time was shortened by more than 2 orders of magnitude compared to the time-domain SH-OCT. The system was applied to image biological tissue of fish scales, pig leg tendon, and rabbit eye sclera. Highly organized collagen fibrils can be visualized in the recorded images. Polarization dependence on the SH has been used to obtain polarization resolved images.
Recent advances in the field of super resolved imaging and sensing
NASA Astrophysics Data System (ADS)
Zalevsky, Zeev; Borkowski, Amikam; Marom, Emanuel; Javidi, Bahram; Beiderman, Yevgeny; Micó, Vicente; García, Javier
2011-05-01
In this paper we start by presenting one recent development in the field of geometric super resolution. The new approach overcomes the reduction of resolution caused by the non ideal sampling of the image done by the spatial averaging of each pixel of the sampling array. Right after, we demonstrate a remote super sensing technique allowing monitoring, from a distance, the heart beats, blood pulse pressure and the glucose level in the blood stream of a patient by tracking the trajectory of secondary speckle patterns reflected from the skin of the wrist or from the sclera.
Whole-globe biomechanics using high-field MRI.
Voorhees, Andrew P; Ho, Leon C; Jan, Ning-Jiun; Tran, Huong; van der Merwe, Yolandi; Chan, Kevin; Sigal, Ian A
2017-07-01
The eye is a complex structure composed of several interconnected tissues acting together, across the whole globe, to resist deformation due to intraocular pressure (IOP). However, most work in the ocular biomechanics field only examines the response to IOP over smaller regions of the eye. We used high-field MRI to measure IOP induced ocular displacements and deformations over the whole globe. Seven sheep eyes were obtained from a local abattoir and imaged within 48 h using MRI at multiple levels of IOP. IOP was controlled with a gravity perfusion system and a cannula inserted into the anterior chamber. T2-weighted imaging was performed to the eyes serially at 0 mmHg, 10 mmHg, 20 mmHg and 40 mmHg of IOP using a 9.4 T MRI scanner. Manual morphometry was conducted using 3D visualization software to quantify IOP-induced effects at the globe scale (e.g. axial length and equatorial diameters) or optic nerve head scale (e.g. canal diameter, peripapillary sclera bowing). Measurement sensitivity analysis was conducted to determine measurement precision. High-field MRI revealed an outward bowing of the posterior sclera and anterior bulging of the cornea due to IOP elevation. Increments in IOP from 10 to 40 mmHg caused measurable increases in axial length in 6 of 7 eyes of 7.9 ± 5.7% (mean ± SD). Changes in equatorial diameter were minimal, 0.4 ± 1.2% between 10 and 40 mmHg, and in all cases less than the measurement sensitivity. The effects were nonlinear, with larger deformations at normal IOPs (10-20 mmHg) than at elevated IOPs (20-40 mmHg). IOP also caused measurable increases in the nasal-temporal scleral canal diameter of 13.4 ± 9.7% between 0 and 20 mmHg, but not in the superior-inferior diameter. This study demonstrates that high-field MRI can be used to visualize and measure simultaneously the effects of IOP over the whole globe, including the effects on axial length and equatorial diameter, posterior sclera displacement and bowing, and even changes in scleral canal diameter. The fact that the equatorial diameter did not change with IOP, in agreement with previous studies, indicates that a fixed boundary condition is a reasonable assumption for half globe inflation tests and computational models. Our results demonstrate the potential of high-field MRI to contribute to understanding ocular biomechanics, and specifically of the effects of IOP in large animal models. Copyright © 2017 Elsevier Ltd. All rights reserved.
Liu, Yan; Wang, Yuexin; Lv, Huibin; Jiang, Xiaodan; Zhang, Mingzhou; Li, Xuemin
2017-01-01
To investigate the efficacy of α-adrenergic agonist brimonidine either alone or combined with pirenzepine for inhibiting progressing myopia in guinea pig lens-myopia-induced models. Thirty-six guinea pigs were randomly divided into six groups: Group A received 2% pirenzepine, Group B received 0.2% brimonidine, Group C received 0.1% brimonidine, Group D received 2% pirenzepine + 0.2% brimonidine, Group E received 2% pirenzepine + 0.1% brimonidine, and Group F received the medium. Myopia was induced in the right eyes of all guinea pigs using polymethyl methacrylate (PMMA) lenses for 3 weeks. Eye drops were administered accordingly. Intraocular pressure was measured every day. Refractive error and axial length measurements were performed once a week. The enucleated eyeballs were removed for hematoxylin and eosin (H&E) and Van Gieson (VG) staining at the end of the study. The lens-induced myopia model was established after 3 weeks. Treatment with 0.1% brimonidine alone and 0.2% brimonidine alone was capable of inhibiting progressing myopia, as shown by the better refractive error (p=0.024; p=0.006) and shorter axial length (p=0.005; p=0.0017). Treatment with 0.1% brimonidine and 0.2% brimonidine combined with 2% pirenzepine was also effective in suppressing progressing refractive error (p=0.016; p=0.0006) and axial length (p=0.017; p=0.0004). The thickness of the sclera was kept stable in all groups except group F; the sclera was much thinner in the lens-induced myopia eyes compared to the control eyes. Treatment with 0.1% brimonidine alone and 0.2% brimonidine alone, as well as combined with 2% pirenzepine, was effective in inhibiting progressing myopia. The result indicates that intraocular pressure elevation is possibly a promising mechanism and potential treatment for progressing myopia.
Cosmetic Preservatives as Therapeutic Corneal and Scleral Tissue Cross-Linking Agents
Babar, Natasha; Kim, MiJung; Cao, Kerry; Shimizu, Yukari; Kim, Su-Young; Takaoka, Anna; Trokel, Stephen L.; Paik, David C.
2015-01-01
Purpose. Previously, aliphatic β-nitroalcohols (BNAs) have been studied as a means to chemically induce tissue cross-linking (TXL) of cornea and sclera. There are a number of related and possibly more potent agents, known as formaldehyde releasers (FARs), that are in commercial use as preservatives in cosmetics and other personal care products. The present study was undertaken in order to screen such compounds for potential clinical utility as therapeutic TXL agents. Methods. A chemical registry of 62 FARs was created from a literature review and included characteristics relevant to TXL such as molecular weight, carcinogenicity/mutagenicity, toxicity, hydrophobicity, and commercial availability. From this registry, five compounds [diazolidinyl urea (DAU), imidazolidinyl urea (IMU), sodium hydroxymethylglycinate (SMG), DMDM hydantoin (DMDM), 5-Ethyl-3,7-dioxa-1-azabicyclo [3.3.0] octane (OCT)] were selected for efficacy screening using two independent systems, an ex vivo rabbit corneal cross-linking simulation setup and incubation of cut scleral tissue pieces. Treatments were conducted at pH 7.4 or 8.5 for 30 minutes. Efficacy was evaluated using thermal denaturation temperature (Tm), and cell toxicity was studied using the trypan blue exclusion method. Results. Cross-linking effects in the five selected FARs were pH and concentration dependent. Overall, the Tm shifts were in agreement with both cornea and sclera. By comparison with BNAs previously reported upon, the FARs identified in this study were significantly more potent but with similar or better cytotoxicity. Conclusions. The FARs, a class of compounds well known to the cosmetic industry, may have utility as therapeutic TXL agents. The compounds studied thus far show promise and will be further tested. PMID:25634979
Targeted Delivery of Antiglaucoma Drugs to the Supraciliary Space Using Microneedles
Kim, Yoo C.; Edelhauser, Henry F.; Prausnitz, Mark R.
2014-01-01
Purpose. In this work, we tested the hypothesis that highly targeted delivery of antiglaucoma drugs to the supraciliary space by using a hollow microneedle allows dramatic dose sparing of the drug compared to topical eye drops. The supraciliary space is the most anterior portion of the suprachoroidal space, located below the sclera and above the choroid and ciliary body. Methods. A single, hollow 33-gauge microneedle, 700 to 800 μm in length, was inserted into the sclera and used to infuse antiglaucoma drugs into the supraciliary space of New Zealand white rabbits (N = 3–6 per group). Sulprostone, a prostaglandin analog, and brimonidine, an α2-adrenergic agonist, were delivered via supraciliary and topical administration at various doses. The drugs were delivered unilaterally, and intraocular pressure (IOP) of both eyes was measured by rebound tonometry for 9 hours after injection to assess the pharmacodynamic responses. To assess safety of the supraciliary injection, IOP change immediately after intravitreal and supraciliary injection were compared. Results. Supraciliary delivery of both sulprostone and brimonidine reduced IOP by as much as 3 mm Hg bilaterally in a dose-related response; comparison with topical administration at the conventional human dose showed approximately 100-fold dose sparing by supraciliary injection for both drugs. A safety study showed that the kinetics of IOP elevation immediately after supraciliary and intravitreal injection of placebo formulations were similar. Conclusions. This study introduced the use of targeted drug delivery to the supraciliary space by using a microneedle and demonstrated dramatic dose sparing of antiglaucoma therapeutic agents compared to topical eye drops. Targeted delivery in this way can increase safety by reducing side effects and could allow a single injection to contain enough drug for long-term sustained delivery. PMID:25212782
NASA Astrophysics Data System (ADS)
Patrón, Verónica A.; Álvarez Borrego, Josué; Coronel Beltrán, Ángel
2015-09-01
Eye tracking has many useful applications that range from biometrics to face recognition and human-computer interaction. The analysis of the characteristics of the eyes has become one of the methods to accomplish the location of the eyes and the tracking of the point of gaze. Characteristics such as the contrast between the iris and the sclera, the shape, and distribution of colors and dark/light zones in the area are the starting point for these analyses. In this work, the focus will be on the contrast between the iris and the sclera, performing a correlation in the frequency domain. The images are acquired with an ordinary camera, which with were taken images of thirty-one volunteers. The reference image is an image of the subjects looking to a point in front of them at 0° angle. Then sequences of images are taken with the subject looking at different angles. These images are processed in MATLAB, obtaining the maximum correlation peak for each image, using two different filters. Each filter were analyzed and then one was selected, which is the filter that gives the best performance in terms of the utility of the data, which is displayed in graphs that shows the decay of the correlation peak as the eye moves progressively at different angle. This data will be used to obtain a mathematical model or function that establishes a relationship between the angle of vision (AOV) and the maximum correlation peak (MCP). This model will be tested using different input images from other subject not contained in the initial database, being able to predict angle of vision using the maximum correlation peak data.
Todokoro, Daisuke; Hoshino, Junki; Yo, Ayaka; Makimura, Koichi; Hirato, Junko; Akiyama, Hideo
2018-02-13
Ubiquitous fungi of the Scedosporium apiospermum species complex (SASC) cause various opportunistic infections. Posterior subtenon triamcinolone acetonide (STTA) injection is a standard therapy for intraocular inflammation and macular edema. We report a case of Scedosporium apiospermum infectious scleritis after a posterior STTA injection. A 75-year-old man received a posterior STTA injection to treat macular edema in his left eye. After 3 months, he complained of ocular pain and hyperemia in his left eye. Examination showed a subtenon abscess in the site corresponding with the STTA injection. After incising the abscess, the smear revealed numerous conidia-like structures. Although we suspected fungal infection and started topical voriconazole (VRCZ) and levofloxacin, the inflammation of the eye worsened. Fungal culture revealed filamentous fungus growth. Subsequently, we added systemic VRCZ and performed surgical debridement of the infected sclera and Tenon's capsule. Pathology of the sclera showed fungal hyphae. The antifungal susceptibility test revealed low minimum inhibitory concentrations for micafungin, VRCZ and miconazole (0.06, 0.25 and 0.5 μg/mL, respectively). After 2 months, the ciliary injection subsided and VRCZ therapy was stopped. However, subtenon abscess recurred 1 month after discontinuation of topical VRCZ. Surgical debridement and topical VRCZ were resumed, with the eye finally improving after 5 months of management. The fungal species was identified as Scedosporium apiospermum sensu stricto morphologically and by DNA sequencing. This case was successfully treated by topical and systemic VRCZ and repeated surgical debridement. Infectious scleritis caused by SASC rarely develops after posterior STTA. SASC can produce conidia in the enclosed subtenon space. Late-onset infectious scleritis after a posterior STTA injection suggests the presence of a fungal infection, including SASC, thereby requiring extensive and prolonged medical and surgical treatment.
Srinivasan, Vivek J.; Adler, Desmond C.; Chen, Yueli; Gorczynska, Iwona; Huber, Robert; Duker, Jay S.; Schuman, Joel S.; Fujimoto, James G.
2009-01-01
Purpose To demonstrate ultrahigh-speed optical coherence tomography (OCT) imaging of the retina and optic nerve head at 249,000 axial scans per second and a wavelength of 1060 nm. To investigate methods for visualization of the retina, choroid, and optic nerve using high-density sampling enabled by improved imaging speed. Methods A swept-source OCT retinal imaging system operating at a speed of 249,000 axial scans per second was developed. Imaging of the retina, choroid, and optic nerve were performed. Display methods such as speckle reduction, slicing along arbitrary planes, en face visualization of reflectance from specific retinal layers, and image compounding were investigated. Results High-definition and three-dimensional (3D) imaging of the normal retina and optic nerve head were performed. Increased light penetration at 1060 nm enabled improved visualization of the choroid, lamina cribrosa, and sclera. OCT fundus images and 3D visualizations were generated with higher pixel density and less motion artifacts than standard spectral/Fourier domain OCT. En face images enabled visualization of the porous structure of the lamina cribrosa, nerve fiber layer, choroid, photoreceptors, RPE, and capillaries of the inner retina. Conclusions Ultrahigh-speed OCT imaging of the retina and optic nerve head at 249,000 axial scans per second is possible. The improvement of ∼5 to 10× in imaging speed over commercial spectral/Fourier domain OCT technology enables higher density raster scan protocols and improved performance of en face visualization methods. The combination of the longer wavelength and ultrahigh imaging speed enables excellent visualization of the choroid, sclera, and lamina cribrosa. PMID:18658089
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rueegsegger, Michael B.; Bach Cuadra, Meritxell; Pica, Alessia
Purpose: Ocular anatomy and radiation-associated toxicities provide unique challenges for external beam radiation therapy. For treatment planning, precise modeling of organs at risk and tumor volume are crucial. Development of a precise eye model and automatic adaptation of this model to patients' anatomy remain problematic because of organ shape variability. This work introduces the application of a 3-dimensional (3D) statistical shape model as a novel method for precise eye modeling for external beam radiation therapy of intraocular tumors. Methods and Materials: Manual and automatic segmentations were compared for 17 patients, based on head computed tomography (CT) volume scans. A 3Dmore » statistical shape model of the cornea, lens, and sclera as well as of the optic disc position was developed. Furthermore, an active shape model was built to enable automatic fitting of the eye model to CT slice stacks. Cross-validation was performed based on leave-one-out tests for all training shapes by measuring dice coefficients and mean segmentation errors between automatic segmentation and manual segmentation by an expert. Results: Cross-validation revealed a dice similarity of 95% {+-} 2% for the sclera and cornea and 91% {+-} 2% for the lens. Overall, mean segmentation error was found to be 0.3 {+-} 0.1 mm. Average segmentation time was 14 {+-} 2 s on a standard personal computer. Conclusions: Our results show that the solution presented outperforms state-of-the-art methods in terms of accuracy, reliability, and robustness. Moreover, the eye model shape as well as its variability is learned from a training set rather than by making shape assumptions (eg, as with the spherical or elliptical model). Therefore, the model appears to be capable of modeling nonspherically and nonelliptically shaped eyes.« less
Transsclera Drug Delivery by Pulsed High-Intensity Focused Ultrasound (HIFU): An Ex Vivo Study.
Murugappan, Suresh Kanna; Zhou, Yufeng
2015-01-01
PURPOSE/AIM OF STUDY: Drug delivery to the ocular posterior segment is of importance, but it is a challenge in the treatment of irreversible blindness disease, such as age-related macular degeneration. Although some methods (i.e. intraocular injection, sustained release by polymer and iontophoresis) have been applied, some technical drawbacks, such as slow rate and damage to the eye, need to be overcome for wide use. In this study, the feasibility of high-intensity focused ultrasound (HIFU) to enhance the transsclera drug delivery was tested for the first time. One-hundred HIFU pulses with the driving frequency of 1.1 MHz, acoustic power of 105.6 W, pulse duration of 10-50 ms and pulse repetition frequency of 1 Hz were delivered to the fresh ex vivo porcine sclera specimen. In comparison to the passive diffusion (control), 50-ms HIFU can increase the penetration depth by 2.0 folds (501.7 ± 126.4 µm versus 252.4 ± 29.2 µm) using bicinchoninic acid assay and Rhodamine 6 G fluorescence intensity by 3.1 folds (22.4 ± 12.3 versus 7.1 ± 4.1) and coverage area by 2.6 folds (40.4 ± 9.1% versus 15.8 ± 2.9%). No morphological changes on the sonicated sclera samples were found using a surface electron microscope. In summary, pulsed-HIFU may be an effective modality in the transsclera drug delivery with a high transporting rate and depth. In vivo studies are necessary to further evaluate its performance, including the drug penetration and its possible side effects.
Wide-field fundus imaging with trans-palpebral illumination.
Toslak, Devrim; Thapa, Damber; Chen, Yanjun; Erol, Muhammet Kazim; Paul Chan, R V; Yao, Xincheng
2017-01-28
In conventional fundus imaging devices, transpupillary illumination is used for illuminating the inside of the eye. In this method, the illumination light is directed into the posterior segment of the eye through the cornea and passes the pupillary area. As a result of sharing the pupillary area for the illumination beam and observation path, pupil dilation is typically necessary for wide-angle fundus examination, and the field of view is inherently limited. An alternative approach is to deliver light from the sclera. It is possible to image a wider retinal area with transcleral-illumination. However, the requirement of physical contact between the illumination probe and the sclera is a drawback of this method. We report here trans-palpebral illumination as a new method to deliver the light through the upper eyelid (palpebra). For this study, we used a 1.5 mm diameter fiber with a warm white LED light source. To illuminate the inside of the eye, the fiber illuminator was placed at the location corresponding to the pars plana region. A custom designed optical system was attached to a digital camera for retinal imaging. The optical system contained a 90 diopter ophthalmic lens and a 25 diopter relay lens. The ophthalmic lens collected light coming from the posterior of the eye and formed an aerial image between the ophthalmic and relay lenses. The aerial image was captured by the camera through the relay lens. An adequate illumination level was obtained to capture wide angle fundus images within ocular safety limits, defined by the ISO 15004-2: 2007 standard. This novel trans-palpebral illumination approach enables wide-angle fundus photography without eyeball contact and pupil dilation.
Crystalline lens MTF measurement during simulated accommodation
NASA Astrophysics Data System (ADS)
Borja, David; Takeuchi, Gaku; Ziebarth, Noel; Acosta, Ana C.; Manns, Fabrice; Parel, Jean-Marie
2005-04-01
Purpose: To design and test an optical system to measure the optical quality of post mortem lenses during simulated accommodation. Methods: An optical bench top system was designed to measure the point spread function and calculate the modulation transfer function (MTF) of monkey and human ex-vivo crystalline lenses. The system consists of a super luminescent diode emitting at 850nm, collimated into a 3mm beam which is focused by the ex-vivo lens under test. The intensity distribution at the focus (point spread function) is re-imaged and magnified onto a beam profiler CCD camera. The optical quality in terms of spatial frequency response (modulation transfer function) is calculated by Fourier transform of the point spread function. The system was used on ex-vivo lenses with attached zonules, ciliary body and sclera. The sclera was glued to 8 separate PMMA segments and stretched radial by 5mm on an accommodation simulating lens stretching device. The point spread function was measured for each lens in the relaxed and stretched state for 5 human (ages 38-86 years) and 5 cynomolgus monkey (ages 53 - 67 months) fresh post mortem crystalline lenses. Results: Stretching induced measurable changes in the MTF. The cutoff frequency increased from 54.4+/-13.6 lp/mm unstretched to 59.5+/-21.4 lp/mm stretched in the post-presbyopic human and from 51.9+/-24.7 lp/mm unstretched to 57.7+/-18.5 lp/mm stretched cynomolgus monkey lenses. Conclusion: The results demonstrate the feasibility of measuring the optical quality of ex-vivo human and cynomolgus monkey lenses during simulated accommodation. Additional experiments are underway to quantify changes in optical quality induced by stretching.
Hydrogel Ring for Topical Drug Delivery to the Ocular Posterior Segment.
Shikamura, Yuko; Yamazaki, Yoshiko; Matsunaga, Toru; Sato, Takao; Ohtori, Akira; Tojo, Kakuji
2016-05-01
To investigate the efficacy of a topical hydrogel ring for drug delivery to the posterior segment of the rabbit eye. Novel hydrogel corneal lenses (CL), scleral/corneal lenses (S/CL), and rings were prepared using poly(hydroxyethyl methacrylate). The devices were immersed in 0.3% ofloxacin ophthalmic solution (OOS) to homogeneously distribute the drug throughout the hydrogel. The medicated CL, S/CL, Ring 1 (standard ring), or Ring 2 (shape-optimized ring) was applied to the surface of the cornea, cornea/bulbar conjunctiva, or bulbar conjunctiva of albino rabbits, respectively. Medicated rings did not touch the corneal surface. In another group, one OOS drop was administered to the eye. After 0.25-8 hours, the hydrogel devices were removed and ocular tissues were harvested. High-performance liquid chromatography (HPLC) was used to measure the ofloxacin concentration in the devices and tissues. The drug concentrations in the posterior segment tissues were compared among ofloxacin delivery methods. One hour after placement, eyes treated with Ring 1 or S/CL had markedly higher ofloxacin levels in the posterior segment tissues (conjunctiva, sclera, and retina/choroid) than eyes treated with topical OOS or a CL. Lower levels of ofloxacin were found in anterior segment tissues (cornea and aqueous humor) in eyes treated with Ring 1 compared to those treated with S/CL. Ring 2 most effectively delivered ofloxacin to the retina/choroid. The tissue ofloxacin concentration in the fellow eye was markedly lower than the eye treated with Ring 2. Our results suggest that hydrogel rings are effective in delivering topical ophthalmic drugs to the posterior segment. The drugs are most likely delivered via the transconjunctival/scleral route by lateral diffusion across the bulbar conjunctiva and through the sclera. Systemic drug delivery to the posterior segment is minimal.
Measuring Deformation in the Mouse Optic Nerve Head and Peripapillary Sclera
Nguyen, Cathy; Midgett, Dan; Kimball, Elizabeth C.; Steinhart, Matthew R.; Nguyen, Thao D.; Pease, Mary E.; Oglesby, Ericka N.; Jefferys, Joan L.; Quigley, Harry A.
2017-01-01
Purpose To develop an ex vivo explant system using multiphoton microscopy and digital volume correlation to measure the full-field deformation response to intraocular pressure (IOP) change in the peripapillary sclera (PPS) and in the optic nerve head (ONH) astrocytic structure. Methods Green fluorescent protein (GFP)-glutamate transporter-GLT1 (GLT1/GFP) mouse eyes were explanted and imaged with a laser-scanning microscope under controlled inflation. Images were analyzed for regional strains and changes in astrocytic lamina and PPS shape. Astrocyte volume fraction in seven control GLT1/GFP mice was measured. The level of fluorescence of GFP fluorescent astrocytes was compared with glial fibrillary acidic protein (GFAP) labeled astrocytes using immunohistochemistry. Results The ONH astrocytic structure remained stable during 3 hours in explants. Control strain—globally, in the central one-half or two-thirds of the astrocytic lamina—was significantly greater in the nasal-temporal direction than in the inferior-superior or anterior-posterior directions (each P ≤ 0.03, mixed models). The PPS opening (perimeter) in normal eye explants also became wider nasal-temporally than superior-inferiorly during inflation from 10 to 30 mm Hg (P = 0.0005). After 1 to 3 days of chronic IOP elevation, PPS area was larger than in control eyes (P = 0.035), perimeter elongation was 37% less than controls, and global nasal-temporal strain was significantly less than controls (P = 0.007). Astrocyte orientation was altered by chronic IOP elevation, with processes redirected toward the longitudinal axis of the optic nerve. Conclusions The explant inflation test measures the strain response of the mouse ONH to applied IOP. Initial studies indicate regional differences in response to both acute and chronic IOP elevation within the ONH region. PMID:28146237
Yang, Hongli; Thompson, Hilary; Roberts, Michael D.; Sigal, Ian A.; Downs, J. Crawford
2011-01-01
Purpose. To retest the hypothesis that monkey ONH connective tissues become hypercompliant in early experimental glaucoma (EEG), by using 3-D histomorphometric reconstructions, and to expand the characterization of EEG connective tissue deformation to nine EEG eyes. Methods. Trephinated ONH and peripapillary sclera from both eyes of nine monkeys that were perfusion fixed, with one normal eye at IOP 10 mm Hg and the other EEG eye at 10 (n = 3), 30 (n = 3), or 45 (n = 3) mm Hg were serial sectioned, 3-D reconstructed, 3-D delineated, and quantified with 3-D reconstruction techniques developed in prior studies by the authors. Overall, and for each monkey, intereye differences (EEG eye minus normal eye) for each parameter were calculated and compared by ANOVA. Hypercompliance in the EEG 30 and 45 eyes was assessed by ANOVA, and deformations in all nine EEG eyes were separately compared by region without regard for fixation IOP. Results. Hypercompliant deformation was not significant in the overall ANOVA, but was suggested in a subset of EEG 30/45 eyes. EEG eye deformations included posterior laminar deformation, neural canal expansion, lamina cribrosa thickening, and posterior (outward) bowing of the peripapillary sclera. Maximum posterior laminar deformation and scleral canal expansion co-localized to either the inferior nasal or superior temporal quadrants in the eyes with the least deformation and involved both quadrants in the eyes achieving the greatest deformation. Conclusions. The data suggest that, in monkey EEG, ONH connective tissue hypercompliance may occur only in a subset of eyes and that early ONH connective tissue deformation is maximized in the superior temporal and/or inferior nasal quadrants. PMID:20702834
Pitfalls in colour photography of choroidal tumours
Schalenbourg, A; Zografos, L
2013-01-01
Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown. PMID:23238442
A SEM-correlation of the anatomy of the vitreous body: making visible the invisible.
Jongebloed, W L; Humalda, D; Worst, J F
1986-12-30
The naked human vitreous (sclera, iris and cornea removed) suspended in water does not reveal inner structures. After ink injection into the vitreous, the presence of different compartments and the existence of cisterns becomes evident. A concept of the internal system of cisterns is given on the basis of stereoscopic-lightmicroscopic images. An attempt is made to correlate images of the complete vitreous body, obtained with a stereo-lightmicroscope, with images of segments of cisternal walls produced with a scanning electron-microscope (SEM). A comparison is made between SEM-images of the vitreous bodies of human and rabbit eyes.
Pitfalls in colour photography of choroidal tumours.
Schalenbourg, A; Zografos, L
2013-02-01
Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown.
Norton, Thomas T.
2012-01-01
Purpose. During the development of, and recovery from, negative lens-induced myopia there is regulated remodeling of the scleral extracellular matrix (ECM) that controls the extensibility of the sclera. Difference gel electrophoresis (DIGE) was used to identify and categorize proteins whose levels are altered in this process. Methods. Two groups of five tree shrews started monocular lens wear 24 days after eye opening (days of visual experience [VE]). The lens-induced myopia (LIM) group wore a −5 D lens for 4 days. The recovery (REC) group wore a −5 D lens for 11 days and then recovered for 4 days. Two normal groups (28 and 39 days of VE; n = 5 each) were also examined, age-matched to each of the treatment groups. Refractive and A-scan measures confirmed the effect of the treatments. Scleral proteins were isolated and resolved by DIGE. Proteins that differed in abundance were identified by mass spectrometry. Ingenuity pathway analysis was used to investigate potential biological pathway interactions. Results. During normal development (28–39 days of VE), eight proteins decreased and one protein increased in relative abundance. LIM-treated eyes were myopic and longer than control eyes; LIM-control eyes were slightly myopic compared with 28N eyes, indicating a yoking effect. In both the LIM-treated and the LIM-control eyes, there was a general downregulation from normal of proteins involved in transcription, cell adhesion, and protein synthesis. Additional proteins involved in cell adhesion, actin cytoskeleton, transcriptional regulation, and ECM structural proteins differed in the LIM-treated eyes versus normal but did not differ in the control eyes versus normal. REC-treated eyes were recovering from the induced myopia. REC-control eye refractions were not significantly different from the 39N eyes, and few proteins differed from age-matched normal eyes. The balance of protein expression in the REC-treated eyes, compared with normal eyes and REC-control eyes, shifted toward upregulation or a return to normal levels of proteins involved in cell adhesion, cell division, cytoskeleton, and ECM structural proteins, including upregulation of several cytoskeleton-related proteins not affected during myopia development. Conclusions. The DIGE procedure revealed new proteins whose abundance is altered during myopia development and recovery. Many of these are involved in cell-matrix adhesions, cytoskeleton, and transcriptional regulation and extend our understanding of the remodeling that controls the extensibility of the sclera. Reductions in these proteins during minus lens wear may produce the increased scleral viscoelasticity that results in faster axial elongation. Recovery is not a mirror image of lens-induced myopia—many protein levels, decreased during LIM, returned to normal, or slightly above normal, and additional cytoskeleton proteins were upregulated. However, no single protein or pathway appeared to be responsible for the scleral changes during myopia development or recovery. PMID:22039233
Radioactive phosphorus uptake test for the diagnosis of malignant melanoma of the choroid
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shields, J.A.; Packer, S.
The most frequently used radioisotope in ophthalmology is radioactive phosphorus (/sup 32/P). Since its introduction into ophthalmology in 1951, it has been used primarily as an aid in the diagnosis of malignant melanoma of the choroid. During the thirty years of clinical use, the indications for this test have been clearly defined. The maximum tissue penetration of /sup 32/P is 7 mm. Surgical dissection is therefore frequently necessary to enable the ophthalmologist to place the Geiger-Muller probe on the sclera in proximity to the tumor. False positive and false negative results are unusual and the test is between 96% andmore » 100% accurate.« less
Osteogenesis imperfecta type I: A case report
REN, JIANMIN; XU, XIAOJIE; JIAN, XIANGDONG; WANG, JIERU
2014-01-01
A 15-year-old male patient was admitted to hospital having experienced repeated fractures over the previous three years, predominantly due to falling down or overexertion. The clinical signs and radiological features, such as recurrent fractures, blue sclera and low bone mineral density (BMD) level, all led to the diagnosis of a mild form of osteogenesis imperfecta (OI) type I. The patient began treatment with a regular intake of calcium (1,000 mg/day), an adequate intake of vitamin D (800 U/day) and intravenous pamidronate (60 mg). Following four months of treatment, the symptoms and quality of life of the patient improved. This patient appears to be a rare case of OI type I. PMID:24926339
A rare combination of amniotic constriction band with osteogenesis imperfecta.
Shah, Krupa Hitesh; Shah, Hitesh
2015-11-11
Amniotic constriction bands and osteogenesis imperfecta are disorders arising from a collagen defect. We report a rare association of amniotic bands with osteogenesis imperfecta in a child. The child was born with multiple amniotic bands involving the right leg, both hands and both feet. Multiple fractures of long bones of lower limbs occurred in childhood due to trivial trauma. Deformities of the femur and tibia due to malunion with osteopenia and blue sclerae were present. The patient was treated with z plasty of constriction band of the right tibia and bisphosphonate for osteogenesis imperfecta. This rare association of both collagen diseases may provide further insight for the pathogenesis of these diseases. 2015 BMJ Publishing Group Ltd.
[Osteogenesis imperfecta in monozygotic twins in Burundi].
Armstrong, O; Karayuba, R; Ngendahayo, L; Habonimana, E
1994-01-01
Little data is available about osteogenesis imperfecta in Black African children. This defect was diagnosed in monozygotic twins from Rwanda who presented multiple fractures, in particular of the femur, when they began to walk. Osteogenesis imperfecta was confirmed by lower limb deformity, presence of wormian bones in the skull, blue sclera, and tooth defects. In addition to the fact that it is uncommon to encounter this condition in monozygotic twins, this case is interesting for several reasons. Was osteogenesis imperfecta in these patients type I, frequent, or type III, exceptional? More importantly, this case stresses the high prevalence of type III in Black Africa which could constitute a hot-bed in the world.
Severe Acanthamoeba sclerokeratitis in a non-contact lens wearer.
Hirano, K; Sai, S
1999-06-01
To report a case of severe Acanthamoeba sclerokeratitis. A 70-year-old male non-contact lens wearer was examined for severe pain in the left eye which began about 40 days after cataract surgery. In spite of a careful search, it required 6 weeks to detect Acanthamoeba. Systemic and topical fluconazol and miconazol did not help and the keratitis progressed into necrotic sclerokeratitis with protrusion of uveal tissue through the thin sclera. Those findings slowly got worse before the Acanthamoeba sclerokeratitis resolved 6 months later with scar formation. We describe the terminal and cicatricial stages of Acanthamoeba keratitis, and report that the healing process can follow the terminal stage and the eye does not need to be enucleated.
SU-F-T-48: Clinical Implementation of Brachytherapy Planning System for COMS Eye Plaques
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ferreira, C; Islam, M; Ahmad, S
Purpose: To commission the Brachytherapy Planning (BP) system (Varian, Palo Alto, CA) for the Collaborative Ocular Melanoma Study (COMS) eye plaques by evaluating dose differences against original plans from Nucletron Planning System (NPS). Methods: NPS system is the primary planning software for COMS-plaques at our facility; however, Brachytherapy Planning 11.0.47 (Varian Medical Systems) is used for secondary check and for seed placement configurations not originally commissioned. Dose comparisons of BP and NPS plans were performed for prescription of 8500 cGy at 5 mm depth and doses to normal structures: opposite retina, inner sclera, macula, optic disk and lens. Plans weremore » calculated for Iodine-125 seeds (OncoSeeds, Model 6711) using COMS-plaques of 10, 12, 14, 16, 18 and 20 mm diameters. An in-house program based on inverse-square was utilized to calculate point doses for comparison as well. Results: The highest dose difference between BP and NPS was 3.7% for the prescription point for all plaques. Doses for BP were higher than doses reported by NPS for all points. The largest percent differences for apex, opposite retina, inner sclera, macula, optic disk, and lens were 3.2%, 0.9%, 13.5%, 20.5%, 15.7% and 2.2%, respectively. The dose calculated by the in-house program was 1.3% higher at the prescription point, and were as high as 42.1%, for points away from the plaque (i.e. opposite retina) when compared to NPS. Conclusion: Doses to the tumor, lens, retina, and optic nerve are paramount for a successful treatment and vision preservation. Both systems are based on TG-43 calculations and assume water medium tissue homogeneity (ρe=1, water medium). Variations seen may result from the different task group versions and/or mathematical algorithms of the software. BP was commissioned to serve as a backup system and it also enables dose calculation in cases where seeds don’t follow conventional placement configuration.« less
Liu, Yan; Wang, Yuexin; Lv, Huibin; Jiang, Xiaodan; Zhang, Mingzhou
2017-01-01
Purpose To investigate the efficacy of α-adrenergic agonist brimonidine either alone or combined with pirenzepine for inhibiting progressing myopia in guinea pig lens–myopia-induced models. Methods Thirty-six guinea pigs were randomly divided into six groups: Group A received 2% pirenzepine, Group B received 0.2% brimonidine, Group C received 0.1% brimonidine, Group D received 2% pirenzepine + 0.2% brimonidine, Group E received 2% pirenzepine + 0.1% brimonidine, and Group F received the medium. Myopia was induced in the right eyes of all guinea pigs using polymethyl methacrylate (PMMA) lenses for 3 weeks. Eye drops were administered accordingly. Intraocular pressure was measured every day. Refractive error and axial length measurements were performed once a week. The enucleated eyeballs were removed for hematoxylin and eosin (H&E) and Van Gieson (VG) staining at the end of the study. Results The lens-induced myopia model was established after 3 weeks. Treatment with 0.1% brimonidine alone and 0.2% brimonidine alone was capable of inhibiting progressing myopia, as shown by the better refractive error (p=0.024; p=0.006) and shorter axial length (p=0.005; p=0.0017). Treatment with 0.1% brimonidine and 0.2% brimonidine combined with 2% pirenzepine was also effective in suppressing progressing refractive error (p=0.016; p=0.0006) and axial length (p=0.017; p=0.0004). The thickness of the sclera was kept stable in all groups except group F; the sclera was much thinner in the lens-induced myopia eyes compared to the control eyes. Conclusions Treatment with 0.1% brimonidine alone and 0.2% brimonidine alone, as well as combined with 2% pirenzepine, was effective in inhibiting progressing myopia. The result indicates that intraocular pressure elevation is possibly a promising mechanism and potential treatment for progressing myopia. PMID:29204068
Guo, Yin; Liu, Li Juan; Tang, Ping; Feng, Yi; Lv, Yan Yun; Wu, Min; Xu, Liang; Jonas, Jost B
2018-03-01
To assess the development and enlargement of the parapapillary gamma zone in school children. This school-based prospective longitudinal study included Chinese children attending grade 1 in 2011 and returning for yearly follow-up examinations until 2016. These examinations consisted of a comprehensive ocular examination with biometry and color fundus photographs. The parents underwent a standardized interview. The parapapillary gamma zone was defined as the area with visible sclera at the temporal optic disc margin, and the optic disc itself was measured on fundus photographs. The study included 294 children (mean age in 2016, 11.4 ± 0.5 years [range, 10-13 years]; mean axial length, 24.1 ± 1.1 mm [range, 21.13-27.29 mm]). In multivariate analysis, larger increases in the gamma zone area during the study period were correlated (coefficient of determination for bivariate analysis [r2], r2 = 0.69) with larger increases in the vertical-to-horizontal disc diameter ratios (P < 0.001; standardized regression coefficient beta [beta], 0.53; nonstandardized regression coefficient B [B], 4.05; 95% confidence intervals [CI], 3.37-4.73), larger axial elongation (P < 0.001; beta, 0.32; B, 0.37; 95% CI, 0.26-0.47), a larger vertical disc diameter at baseline (P < 0.001; beta, 0.22; B, 0.98; 95% CI, 0.62-1.33), a larger gamma zone area at baseline (P < 0.001; beta, 0.14; B, 0.41; 95% CI, 0.17-0.64), and more time spent indoors studying (P = 0.015; beta, 0.10; B, 0.09; 95% CI, 0.02-0.17). The development and enlargement of the gamma zone in the temporal parapapillary region were associated with an optic disc rotation around the vertical disc axis as indicated by an increasing vertical-to-horizontal disc diameter ratio. These morphologic findings fit with the notion of a backward pull of the temporal peripapillary sclera through the optic nerve dura mater in axially elongated eyes.
Orbital implants in retinoblastoma patients: 23 years of experience and a review of the literature.
Mourits, Daphne L; Moll, Annette C; Bosscha, Machteld I; Tan, H Stevie; Hartong, Dyonne T
2016-03-01
To evaluate complications of different types of orbital implants following enucleation for retinoblastoma. We performed a retrospective chart study of all patients that underwent enucleation as treatment of retinoblastoma between April 1991 and June 2013. Events of implant exposure, extrusion (defined as a complete loss of the implant, or a major exposure that could not be closed) and socket abnormalities were analysed for association with implant type and influence of additional external beam radiation therapy (EBRT) and/or chemotherapy. A total of 224 enucleations in 216 patients (eight bilateral) were identified. Mean age at surgery was 1.9 (median 1.5) years. Of the 219 included enucleated eyes, 20 were not replaced by a primary implant and 18 were replaced by an Allen implant. Scleral wrapped hydroxyapatite (HA) and acrylic implants (polymethylmethacrylate) were inserted in, respectively, 79 and 102 cases. In the total population, 29 treatment or implant-specific events (13.2%) were registered. Main complications were implant exposure n = 10 (4.6%) and extrusion n = 6 (2.7%). The acrylic/sclera group had less exposures or extrusions (5 of 102, 4.9%) compared to the HA/sclera group (10 of 79, 12.7%), although this difference did not quite reach statistical significance (p = 0.06). Additional treatment (chemotherapy and/or EBRT for the fellow eye) was administered in 78 cases (35.8%). The overall complication rate in the entire study population was significantly higher (16.7% versus 5.7%) in the group exposed to additional therapy (OR 3.3; 95% CI 1.30-8.36 p = 0.008). This negative effect of additional therapy was also significant in the combined acrylic/HA group (OR 2.9; 95% CI 0.97-8.46 p = 0.048). Our results suggest a favourable outcome for acrylic implants compared to the HA implant. Additional treatment with chemotherapy and/or EBRT is associated with an increased risk of complications. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
Matsuo, Toshihiko; Takeda, Yoshimasa; Ohtsuka, Aiji
2013-01-01
The purpose of this study was to develop a series of stereoscopic anatomical images of the eye and orbit for use in the curricula of medical schools and residency programs in ophthalmology and other specialties. Layer-by-layer dissection of the eyelid, eyeball, and orbit of a cadaver was performed by an ophthalmologist. A stereoscopic camera system was used to capture a series of anatomical views that were scanned in a panoramic three-dimensional manner around the center of the lid fissure. The images could be rotated 360 degrees in the frontal plane and the angle of views could be tilted up to 90 degrees along the anteroposterior axis perpendicular to the frontal plane around the 360 degrees. The skin, orbicularis oculi muscle, and upper and lower tarsus were sequentially observed. The upper and lower eyelids were removed to expose the bulbar conjunctiva and to insert three 25-gauge trocars for vitrectomy at the location of the pars plana. The cornea was cut at the limbus, and the lens with mature cataract was dislocated. The sclera was cut to observe the trocars from inside the eyeball. The sclera was further cut to visualize the superior oblique muscle with the trochlea and the inferior oblique muscle. The eyeball was dissected completely to observe the optic nerve and the ophthalmic artery. The thin bones of the medial and inferior orbital wall were cracked with a forceps to expose the ethmoid and maxillary sinus, respectively. In conclusion, the serial dissection images visualized aspects of the local anatomy specific to various procedures, including the levator muscle and tarsus for blepharoptosis surgery, 25-gauge trocars as viewed from inside the eye globe for vitrectomy, the oblique muscles for strabismus surgery, and the thin medial and inferior orbital bony walls for orbital bone fractures.
A comparative study of the ocular skeleton of fossil and modern chondrichthyans
Pilgrim, Brettney L; Franz-Odendaal, Tamara A
2009-01-01
Many vertebrates have an ocular skeleton composed of cartilage and/or bone situated within the sclera of the eye. In this study we investigated whether modern and fossil sharks have an ocular skeleton, and whether it is conserved in morphology. We describe the scleral skeletal elements of three species of modern sharks and compare them to those found in fossil sharks from the Cleveland Shale (360 Mya). We also compare the elements to contemporaneous arthrodires from the same deposit. Surprisingly, the morphology of the skeletal support of the eye was found to differ significantly between modern and fossil sharks. All three modern shark species examined (spiny dogfish shark Squalus acanthias, porbeagle shark Lamna nasus and blue shark Prionace glauca) have a continuous skeletal element that encapsulates much of the eyeball; however, the tissue composition is different in each species. Histological and morphological examination revealed scleral cartilage with distinct tesserae in parts of the sclera of the porbeagle and blue shark, and more diffuse calcification in the dogfish. Strengthening of the scleral cartilage by means of tesserae has not been reported previously in the shark eye. In striking contrast, the ocular skeleton of fossil sharks comprises a series of individual elements that are arranged in a ring, similar to the arrangement in modern and fossil reptiles. Fossil arthrodires also have a multi-unit sclerotic ring but these are composed of fewer elements than in fossil sharks. The morphology of these elements has implications for the behaviour and visual capabilities of sharks that lived during the Devonian Period. This is the first time that such a dramatic variation in the morphology of scleral skeletal elements has been observed in a single lineage (Chondrichthyes), making this lineage important for broadening our understanding of the evolution of these elements within jawed vertebrates. PMID:19538630
Guo, Lin; Frost, Michael R; Siegwart, John T; Norton, Thomas T
2014-01-01
During postnatal refractive development, the sclera receives retinally generated signals that regulate its biochemical properties. Hyperopic refractive error causes the retina to produce "GO" signals that, through the direct emmetropization pathway, cause scleral remodeling that increases the axial elongation rate of the eye, reducing the hyperopia. Myopia causes the retina to generate "STOP" signals that produce scleral remodeling, slowing the axial elongation rate and reducing the myopia. Our aim was to compare the pattern of gene expression produced in the sclera by the STOP signals with the GO gene expression signature we described previously. The GO gene expression signature was produced by monocular -5 diopter (D) lens wear for 2 days (ML-2) or 4 days (ML-4); an additional "STAY" condition was examined after eyes had fully compensated for a -5 D lens after 11 days of lens wear (ML-11). After 11 days of -5 D lens wear had produced full refractive compensation, gene expression in the STOP condition was examined during recovery (without the lens) for 2 days (REC-2) or 4 days (REC-4). The untreated contralateral eyes served as a control in all groups. Two age-matched normal groups provided a comparison with the treated groups. Quantitative real-time PCR was used to measure mRNA levels for 55 candidate genes. The STAY group compensated fully for the lens (treated eye versus control eye, -5.1±0.2 D). Wearing the lens, the hyperopic signal for elongation had dissipated (-0.3±0.3 D). In the STOP groups, the refraction in the recovering eyes became less myopic relative to the control eyes (REC-2, +1.3±0.3 D; REC-4, +2.6±0.4 D). In the STAY group, three genes showed significant downregulation. However, many genes that were significantly altered in GO showed smaller, nonsignificant, expression differences in the same direction in STAY, suggesting the gene expression signature in STAY is a greatly weakened form of the GO signature. In the STOP groups, a different gene expression pattern was observed, characterized by mostly upregulation with larger fold differences after 4 days than after 2 days of recovery. Eleven of the 55 genes examined showed significant bidirectional GO/STOP regulation in the ML-2 and REC-2 groups, and 13 genes showed bidirectional regulation in the ML-4 and REC-4 groups. Eight of these genes (NPR3, CAPNS1, NGEF, TGFB1, CTGF, NOV, TIMP1, and HS6ST1) were bidirectionally regulated at both time points in the GO and STOP conditions. An additional 15 genes showed significant regulation in either GO or STOP conditions but not in both. Many genes are involved in scleral remodeling and the control of axial length. The STOP (recovery) gene expression signature in the sclera involves some of the same genes, bidirectionally regulated, as the GO signature. However, other genes, regulated in GO, are not differentially regulated in STOP, and others show differential regulation only in STOP.
Conjunctival erosion after glaucoma drainage device surgery: a feasible option.
Dubey, Suneeta; Prasanth, Baswati; Acharya, Manisha C; Narula, Ritesh
2013-07-01
Glaucoma drainage devices (GDDs) have been used in the management of complicated glaucomas. GDDs are associated with various complications such as tube migration, tube or plate exposure or extrusion, ocular motility disturbance and infection. Erosion of conjunctiva and exposure of the GDD remains a risk factor for the development of endophthalmitis. A wide range of materials have been used for this purpose, including sclera, dura, pericardium, fascia lata and cornea. However, there is no evidence to prove that any of these methods is superior to another for providing tectonic durability in the long term. In this report, we present a case of neovascular glaucoma, who developed conjunctival melting over the tube of an Ahmed Glaucoma Valve implant and was successfully managed with Cap Doxycycline.
Zoonotic ocular onchocercosis caused by Onchocerca lupi in dogs in Romania.
Tudor, Poliana; Turcitu, Mihai; Mateescu, Cosmin; Dantas-Torres, Filipe; Tudor, Niculae; Bărbuceanu, Florica; Ciuca, Lavinia; Burcoveanu, Ioana; Acatrinei, Dumitru; Rinaldi, Laura; Mateescu, Romanița; Bădicu, Adina; Ionașcu, Iuliana; Otranto, Domenico
2016-02-01
Onchocerca lupi is a filarial nematode, which infects the scleral conjunctival tissue of dogs, wolves and cats. Whilst adult nematodes localize in the conjunctive tissue of sclera or in the retrobulbar, microfilariae are found in the skin, and they are rarely diagnosed in asymptomatic animals. Since the first report of human ocular infection 5 years ago, up to 10 zoonotic cases have been identified in patients worldwide. We report, for the first time in Romania, three cases of canine ocular onchocercosis in dogs. Fragments of the harvested worms were characterized morphologically and molecularly. This article expands knowledge on the distribution of this parasite in Eastern Europe and sounds an alarm bell for ophthalmologists about the possible occurrence of human cases of O. lupi infection.
NASA Astrophysics Data System (ADS)
Zimnyakov, Dmitry A.; Tuchin, Valery V.; Yodh, Arjun G.; Mishin, Alexey A.; Peretochkin, Igor S.
1998-04-01
Relationships between decorrelation and depolarization of coherent light scattered by disordered media are examined by using the conception of the photon paths distribution functions. Analysis of behavior of the autocorrelation functions of the scattered field fluctuations and their polarization properties allows us to introduce generalized parameter of scattering media such as specific correlation time. Determination of specific correlation time has been carried out for phantom scattering media (water suspensions of polystyrene spheres). Results of statistical, correlation and polarization analysis of static and dynamic speckle patterns carried out in the experiments with human sclera with artificially controlled optical transmittance are presented. Some possibilities of applications of such polarization- correlation technique for monitoring and visualization of non- single scattering tissue structures are discussed.
Osteogenesis imperfecta: diagnosis and treatment.
Burnei, Gheorghe; Vlad, Costel; Georgescu, Ileana; Gavriliu, Traian Stefan; Dan, Daniela
2008-06-01
Osteogenesis imperfecta is a heritable disorder characterized by extremely fragile bones, blue sclerae, dentinogenesis imperfecta, hearing loss, and scoliosis. In 1979, Sillence classified the condition into four types based on genetic and clinical criteria. Three more classifications have subsequently been added. Diagnosis of osteogenesis imperfecta may be done prenatally (in severe cases), clinically, radiographically, or via biochemical or genetic examination. Medical treatment consists of bisphosphonate use, even in patients younger than age 2 years. Surgical treatment consists of internal splinting of long bones. Research is currently being done on the use of smart intramedullary rods (ie, composed of nitinol shape-memory alloy) for correction of bone deformity and on the use of bone marrow transplantation to increase osteoblast density, thereby reducing fracture frequency.
Yin, Hong-xia; Huang, Zhi-feng; Wang, Zhen-chang; Liu, Zhao-hui; Li, Yong; Zhu, Pei-ping
2010-03-23
To study the application of DEI technique in imaging the small structures of rabbit eyeball. DEI technique was used to image the eyeball of New Zealand white rabbit in vitro. The experiments were performed using beamline 4W1A at the topography station of Beijing Synchrotron Radiation Facility (BSRF). DEI image showed clearly the fine structures of the rabbit eyeball, such as the transparent cornea, the sclera, the ciliaris, and the ciliary body. DEI is a new X-ray imaging modality which achieves high contrast and spatial resolution. It also showed obvious effect of edge enhancement. DEI has good potential in observing the micro-structures of eyeballs and other small organs.
The genetic implication of scoliosis in osteogenesis imperfecta: a review
Liu, Gang; Chen, Jia; Zhou, Yangzhong; Zuo, Yuzhi; Liu, Sen; Chen, Weisheng
2017-01-01
Osteogenesis imperfecta (OI) is a kind of heritable connective tissue disorder, including blue sclerae, hearing loss, skeletal dysplasia causing bone fragility and deformities. It is typically caused by collagen related gene mutations, which could lead to bone formation abnormalities. Scoliosis is one of the most common and severe spinal phenotype which has been reported in approximately 26–74.5% of all OI patients. Recent breakthroughs have suggested that OI can be divided into more than 16 types based on genetic mutations with different degrees of scoliosis. In this review, we summarize the etiology of scoliosis in OI, especially the genetic studies of different types. We aim to provide a systematic review of the genetic etiology and clinical suggestions of scoliosis in OI. PMID:29354746
NASA Astrophysics Data System (ADS)
Tian, Chao; Zhang, Wei; Nguyen, Van Phuc; Huang, Ziyi; Wang, Xueding; Paulus, Yannis M.
2018-02-01
Most reported photoacoustic ocular imaging work to date uses small animals, such as mice and rats, the eyes of which are small and less than one-third the size of a human eye, which poses a challenge for clinical translation. Here we achieved chorioretinal imaging of larger animals, i.e. rabbits, using a dual-modality photoacoustic microscopy (PAM) and optical coherence tomography (OCT) system. Preliminary experimental results in living rabbits demonstrate that the PAM can noninvasively visualize depth-resolved retinal and choroidal vessels using a safe laser exposure dose; and the OCT can finely distinguish different retinal layers, the choroid, and the sclera. This reported work might be a major step forward in clinical translation of photoacoustic microscopy.
Current Management of Presbyopia
Papadopoulos, Pandelis A.; Papadopoulos, Alexandros P.
2014-01-01
Presbyopia is a physiologic inevitability that causes gradual loss of accommodation during the fifth decade of life. The correction of presbyopia and the restoration of accommodation are considered the final frontier of refractive surgery. Different approaches on the cornea, the crystalline lens and the sclera are being pursued to achieve surgical correction of this disability. There are however, a number of limitations and considerations that have prevented widespread acceptance of surgical correction for presbyopia. The quality of vision, optical and visual distortions, regression of effect, complications such as corneal ectasia and haze, anisometropia after monovision correction, impaired distance vision and the invasive nature of the currently techniques have limited the utilization of presbyopia surgery. The purpose of this paper is to provide an update of current procedures available for presbyopia correction and their limitations. PMID:24669140
Gilger, Brian C; Mandal, Abhirup; Shah, Sujay; Mitra, Ashim K
2014-01-01
Subconjunctival/episcleral, intrascleral, and suprachoroidal routes of drug delivery for treatment of posterior segment eye diseases have become more feasible and popular in the past few years. These routes have the advantage of bypassing the main barriers to topical drug penetration, the ocular surface epithelium, the conjunctivallymphatics, and in the case of deep intrascleral and suprachoroidial delivery, the sclera barrier. Many ocular drug delivery application devices, drug delivery methods, and therapeutics that have been developed for intravitreal use can also be used subconjunctivally, intrasclerally, and in the suprachoroidal space. Alternatively, site-specific devices, such microneedles, and therapeutics, such as hydrogel matrices, have been developed to enhance ocular drug delivery. This manuscript will review the recent research advances and patents on episcleral, intrascleral, and suprachoroidal routes of ocular drug delivery.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Asadi, Somayeh; Masoudi, Seyed Farhad, E-mail: masoudi@kntu.ac.ir; Shahriari, Majid
In ophthalmic brachytherapy dosimetry, it is common to consider the water phantom as human eye anatomy. However, for better clinical analysis, there is a need for the dose determination in different parts of the eye. In this work, a full human eye is simulated with MCNP-4C code by considering all parts of the eye, i.e., the lens, cornea, retina, choroid, sclera, anterior chamber, optic nerve, and bulk of the eye comprising vitreous body and tumor. The average dose in different parts of this full model of the human eye is determined and the results are compared with the dose calculatedmore » in water phantom. The central axes depth dose and the dose in whole of the tumor for these 2 simulated eye models are calculated as well, and the results are compared.« less
Yang, Ji-Wen; Xu, Yan-Chun; Sun, Lin; Tian, Xiao-Dan
2010-01-01
AIM To investigate 5-hydroxytryptamine (5-HT) function and 5-HT receptor 2A (5-HT2A) mRNA expression in the formation of lens-induced myopia (LIM). METHODS Lens-induced myopia construction method was applied to generate myopia on guinea pig right eye (LIM eye). RESULTS LIM eyes formed significant myopia with longer axial length. 5-HT level in retina, choroids and sclera from LIM eyes was significantly higher than that in control group. 5-HT2A mRNA expression was also significantly up-regulated. CONCLUSION Refraction lens could induce myopia in guinea pig and 5-HT may play an important role in the formation of myopia by binding with 5-HT2A receptor. PMID:22553578
Ocular and orbital porcupine quills in the dog: a review and case series.
Grahn, B H; Szentimrey, D; Pharr, J W; Farrow, C S; Fowler, D
1995-01-01
A retrospective evaluation of 5 cases of orbital or intraocular porcupine quills in the dog and a literature review from MEDLINE (1983-1995) is presented. This paper reviews the diagnosis, therapy, and visual prognosis of ocular and orbital quills in the dog. Distinguishing penetration and perforation of the eye and intraocular structures is paramount in establishing a visual prognosis and appropriate therapy. Perforation of the cornea or sclera, lens, or the uvea and retina necessitates prompt specialized surgical therapy to save vision. The diagnosis of orbital quills can be readily confirmed with ultrasonography. The characteristic sonographic appearance of a double-banded, linear, hyperechoic object allows accurate localization of the quill, which aids surgical removal. Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. PMID:7585434
Khansari, Maziyar M; O’Neill, William; Penn, Richard; Chau, Felix; Blair, Norman P; Shahidi, Mahnaz
2016-01-01
The conjunctiva is a densely vascularized mucus membrane covering the sclera of the eye with a unique advantage of accessibility for direct visualization and non-invasive imaging. The purpose of this study is to apply an automated quantitative method for discrimination of different stages of diabetic retinopathy (DR) using conjunctival microvasculature images. Fine structural analysis of conjunctival microvasculature images was performed by ordinary least square regression and Fisher linear discriminant analysis. Conjunctival images between groups of non-diabetic and diabetic subjects at different stages of DR were discriminated. The automated method’s discriminate rates were higher than those determined by human observers. The method allowed sensitive and rapid discrimination by assessment of conjunctival microvasculature images and can be potentially useful for DR screening and monitoring. PMID:27446692
Huge corneal dermoid in a well-formed eye: a case report and review of the literature.
Mohammad, Abd-Elnasser A; Kroosh, Sana S
2002-12-01
A 25-day-old boy presented with a left corneal mass and left nasal obstruction. The mass involved the entire cornea with a skin-like surface and protruded outside the palpebral fissure. CT of the orbits disclosed a large cyst coating the entire left cornea, in an eye with a well-formed anterior chamber and a clearly evident lens. CT also revealed left nasal meningo-encephalocele. The eye with the mass was excised. The histopathologic report confirmed the diagnosis of corneal dermoid in an otherwise normally developed eye. This report of a huge dermoid involving the entire corneal diameter and extending into the sclera without ocular alteration posterior to Descemet's membrane is the first such report in the literature. The literature on corneal dermoids is also reviewed.
Karimi, Alireza; Razaghi, Reza; Navidbakhsh, Mahdi; Sera, Toshihiro; Kudo, Susumu
2016-05-01
In spite the fact that a very small human body surface area is comprised by the eye, its wounds due to detonation have recently been dramatically amplified. Although many efforts have been devoted to measure injury of the globe, there is still a lack of knowledge on the injury mechanism due to Primary Blast Wave (PBW). The goal of this study was to determine the stresses and deformations of the human eye components, including the cornea, aqueous, iris, ciliary body, lens, vitreous, retina, sclera, optic nerve, and muscles, attributed to PBW induced by trinitrotoluene (TNT) explosion via a Lagrangian-Eulerian computational coupling model. Magnetic Resonance Imaging (MRI) was employed to establish a Finite Element (FE) model of the human eye according to a normal human eye. The solid components of the eye were modelled as Lagrangian mesh, while an explosive TNT, air domain, and aqueous were modelled using Arbitrary Lagrangian-Eulerian (ALE) mesh. Nonlinear dynamic FE simulations were accomplished using the explicit FE code, namely LS-DYNA. In order to simulate the blast wave generation, propagation, and interaction with the eye, the ALE formulation with Jones-Wilkins-Lee (JWL) equation defining the explosive material were employed. The results revealed a peak stress of 135.70kPa brought about by detonation upsurge on the cornea at the distance of 25cm. The highest von Mises stresses were observed on the sclera (267.3kPa), whereas the lowest one was seen on the vitreous body (0.002kPa). The results also showed a relatively high resultant displacement for the macula as well as a high variation for the radius of curvature for the cornea and lens, which can result in both macular holes, optic nerve damage and, consequently, vision loss. These results may have implications not only for understanding the value of stresses and strains in the human eye components but also giving an outlook about the process of PBW triggers damage to the eye. Copyright © 2016 Elsevier Ltd. All rights reserved.
Optic Nerve Sheath Mechanics and Permeability in VIIP Syndrome
NASA Technical Reports Server (NTRS)
Raykin, Julia; Best, Lauren; Gleason, Rudy; Mulugeta, Lealem; Myers, Jerry; Nelson, Emily; Samuels, Brian C.; Ethier, C. R.
2014-01-01
Long-duration space flight carries the risk of developing Visual Impairment and Intracranial Pressure (VIIP) syndrome, a spectrum of ophthalmic changes including posterior globe flattening, choroidal folds, distension of the optic nerve sheath (ONS), optic nerve kinking and potentially permanent degradation of visual function. The slow onset of VIIP, its chronic nature, and certain clinical features strongly suggest that biomechanical factors acting on the ONS play a role in VIIP. Here we measure several relevant ONS properties needed to model VIIP biomechanics. The ONS (meninges) of fresh porcine eyes (n7) was reflected, the nerve proper was truncated near the sclera, and the meninges were repositioned to create a hollow cylinder of meningeal connective tissue attached to the posterior sclera. The distal end was cannulated, sealed, and pressure clamped (mimicking cerebrospinal fluid [CSF] pressure), while the eye was also cannulated for independent control of intraocular pressure (IOP). The meninges were inflated (CSF pressure cycling 7-50 mmHg) while ONS outer diameter was imaged. In another set of experiments (n4), fluid permeation rate across the meninges was recorded by observing the drainage of an elevated fluid reservoir (30 mmHg) connected to the meninges. The ONS showed behavior typical of soft tissues: viscoelasticity, with hysteresis in early preconditioning cycles and repeatable behavior after 4 cycles, and nonlinear stiffening, particularly at CSF pressures 15 mmHg (Figure). Tangent moduli measured from the loading curve were 372 101, 1199 358, and 2050 379 kPa (mean SEM) at CSF pressures of 7, 15 and 30 mmHg, respectively. Flow rate measurements through the intact meninges at 30mmHg gave a permeability of 1.34 0.46 lmincm2mmHg (mean SEM). The ONS is a tough, strain-stiffening connective tissue that is surprisingly permeable. The latter observation suggests that there could be significant CSF drainage through the ONS into the orbit, likely important for CSF transport in the optic nerve. These experimental measurements, extended to human eyes, are informing computational models of the pathophysiology and biomechanics of the ONS in VIIP syndrome.
Biomechanics of the Optic Nerve Sheath in VIIP Syndrome
NASA Technical Reports Server (NTRS)
Ethier, C. Ross; Raykin, Julia; Gleason, Rudy; Mulugeta, Lealem; Myers, Jerry; Nelson, Emily; Samuels, Brian C.
2014-01-01
Long-duration space flight carries the risk of developing Visual Impairment and Intracranial Pressure (VIIP) syndrome, a spectrum of ophthalmic changes including posterior globe flattening, choroidal folds, distension of the optic nerve sheath (ONS), optic nerve kinking and potentially permanent degradation of visual function. The slow onset of VIIP, its chronic nature, and certain clinical features strongly suggest that biomechanical factors acting on the ONS play a role in VIIP. Here we measure several relevant ONS properties needed to model VIIP biomechanics. The ONS (meninges) of fresh porcine eyes (n7) was reflected, the nerve proper was truncated near the sclera, and the meninges were repositioned to create a hollow cylinder of meningeal connective tissue attached to the posterior sclera. The distal end was cannulated, sealed, and pressure clamped (mimicking cerebrospinal fluid [CSF] pressure), while the eye was also cannulated for independent control of intraocular pressure (IOP). The meninges were inflated (CSF pressure cycling 7-50 mmHg) while ONS outer diameter was imaged. In another set of experiments (n4), fluid permeation rate across the meninges was recorded by observing the drainage of an elevated fluid reservoir (30 mmHg) connected to the meninges. The ONS showed behavior typical of soft tissues: viscoelasticity, with hysteresis in early preconditioning cycles and repeatable behavior after 4 cycles, and nonlinear stiffening, particularly at CSF pressures 15 mmHg (Figure). Tangent moduli measured from the loading curve were 372 101, 1199 358, and 2050 379 kPa (mean SEM) at CSF pressures of 7, 15 and 30 mmHg, respectively. Flow rate measurements through the intact meninges at 30mmHg gave a permeability of 1.34 0.46 lmincm2mmHg (mean SEM). The ONS is a tough, strain-stiffening connective tissue that is surprisingly permeable. The latter observation suggests that there could be significant CSF drainage through the ONS into the orbit, likely important for CSF transport in the optic nerve. These experimental measurements, extended to human eyes, are informing computational models of the pathophysiology and biomechanics of the ONS in VIIP syndrome.
An extraocular non-invasive transscleral LED-endoilluminator for eye speculum integration.
Kölbl, Philipp Simon; Lindner, Christoph; Lingenfelder, Christian; Deuchler, Svenja; Singh, Pankaj; Koch, Frank; Hessling, Martin
2015-09-01
Conventional chandelier-endoilluminators used for pars-plana vitrectomy consist of a light-emitting tip attached to an optical fibre. The tip requires introduction into the ocular space through an incision. To achieve complete illumination of the intraocular space, the introduction of more than just one tip is sometimes necessary. An extraocular vitreoretinal LED-endoilluminator discussed in this paper represents a new approach to illuminate the intraocular space. The light source is integrated into a speculum and firmly apposed to the sclera. This approach offers the advantage of effectively illuminating the interior of the eye even though the procedure is non-invasive. Furthermore, this approach significantly reduces the risk of damage to the retina by phototoxic effects. A round white LED was used as a light source. By integrating the light source into a speculum, the LED was firmly held against the sclera. Thus, the ocular space was illuminated transsclerally. As a result, indirect uniform illumination of the complete intraocular space was achieved. The prototype was developed considering the relevant international standards. Porcine eyes were used because their properties are similar to those of human eyes. Porcine eyes could be acceptably illuminated with the selected LED. The LED-endoilluminator conforms with international standards for endoillumination. Thus, possible photochemical and thermal risks are considered and reduced to a minimum. A novel LED-endoilluminator which can be attached to a speculum was developed. The system does not need any connection to an external light source and, consequently, also avoids usage of an optical fibre. Regular and uniform illumination of the intraocular space was achieved by transmitted and scattered visible irradiation, avoiding an incision. The duration of potential light exposure, compared to existing illumination systems, can be significantly increased. This is also true when the illuminator is not directly placed over the pars-plana and the distance to the retina is reduced. Only a part of the light reaches the retina and the fraction of short wavelength becomes very small. Increased safety of the system results from now being able to increase the exposure time and reduce phototoxic stress to the retina.
Comparison of 16 mm OSU‐Nag and COMS eye plaques
Davidorf, Frederick; Qi, Yujin
2012-01-01
OSU‐NAG eye plaques use fewer sources than COMS‐plaques of comparable size, and do not employ a Silastic seed carrier insert. Monte Carlo modeling was used to calculate 3D dose distributions for a 16 mm OSU‐NAG eye plaque and a 16 mm COMS eye plaque loaded with either Iodine‐125 or Cesium‐131 brachytherapy sources. The OSU‐NAG eye plaque was loaded with eight sources forming two squares, whereas the COMS eye plaque was loaded with thirteen sources approximating three isocentric circles. A spherical eyeball 24.6 mm in diameter and an ellipsoid‐like tumor 6 mm in height and 12 mm in the major and minor axes were used to evaluate the doses delivered. To establish a fair comparison, a water seed carrier was used instead of the Silastic seed carrier designed for the traditional COMS eye plaque. Calculations were performed on the dose distributions along the eye plaque axis and the DVHs of the tumor, as well as the 3D distribution. Our results indicated that, to achieve a prescription dose of 85 Gy at 6 mm from the inner sclera edge for a six‐day treatment, the OSU‐NAG eye plaque will need 6.16 U/source and 6.82 U/source for 125I and 131Cs, respectively. The COMS eye plaque will require 4.02 U/source and 4.43 U/source for the same source types. The dose profiles of the two types of eye plaques on their central axes are within 9% difference for all applicable distances. The OSU‐NAG plaque delivers about 10% and 12% more dose than the COMS for 125I and 131Cs sources, respectively, at the inner sclera edge, but 6% and 3% less dose at the opposite retina. The DVHs of the tumor for two types of plaques were within 6% difference. In conclusion, the dosimetric quality of the OSU‐NAG eye plaque used in eye plaque brachytherapy is comparable to the COMS eye plaque. PACS number: 87.56B, 87.55k, 87.55kh PMID:22584165
Rat optic nerve head anatomy within 3D histomorphometric reconstructions of normal control eyes.
Pazos, Marta; Yang, Hongli; Gardiner, Stuart K; Cepurna, William O; Johnson, Elaine C; Morrison, John C; Burgoyne, Claude F
2015-10-01
The purpose of this study is to three-dimensionally (3D) characterize the principal macroscopic and microscopic relationships within the rat optic nerve head (ONH) and quantify them in normal control eyes. Perfusion-fixed, trephinated ONH from 8 normal control eyes of 8 Brown Norway Rats were 3D histomorphometrically reconstructed, visualized, delineated and parameterized. The rat ONH consists of 2 scleral openings, (a superior neurovascular and inferior arterial) separated by a thin connective tissue strip we have termed the "scleral sling". Within the superior opening, the nerve abuts a prominent extension of Bruch's Membrane (BM) superiorly and is surrounded by a vascular plexus, as it passes through the sclera, that is a continuous from the choroid into and through the dural sheath and contains the central retinal vein (CRV), (inferiorly). The inferior scleral opening contains the central retinal artery and three long posterior ciliary arteries which obliquely pass through the sclera to obtain the choroid. Bruch's Membrane Opening (BMO) is irregular and vertically elongated, enclosing the nerve (superiorly) and CRV and CRA (inferiorly). Overall mean BMO Depth, BMO Area, Choroidal Thickness and peripapillary Scleral Thickness were 29 μm, 56.5 × 10(3) μm(2), 57 μm and 104 μm respectively. Mean anterior scleral canal opening (ASCO) and posterior scleral canal opening (PSCO) radii were 201 ± 15 μm and 204 ± 16 μm, respectively. Mean optic nerve area at the ASCO and PSCO were 46.3 × 10(3)±4.4 × 10(3) μm(2) and 44.1 × 10(3)±4.5 × 10(3) μm(2) respectively. In conclusion, the 3D complexity of the rat ONH and the extent to which it differs from the primate have been under-appreciated within previous 2D studies. Properly understood, these anatomic differences may provide new insights into the relative susceptibilities of the rat and primate ONH to elevated intraocular pressure. Copyright © 2015 Elsevier Ltd. All rights reserved.
[Application value of corneal hysteresis in diagnosis and treatment of glaucoma].
He, L Y; Liang, L; Zhu, M N
2017-02-11
Glaucoma is the first leading cause of irreversible blindness world widely, but the pathogenesis was still unclear. The collagen fibers from cornea and sclera connect to each other and both of them have similar extracellular matrix components. The biomechanical characteristics of optic nerve lamina cribrosa may associated with the biomechanical properties of the cornea. Therefore, the study of corneal physiological can indirectly reflex the compression and damage in optic nerve lamina cribrosa. The technical developments in corneal hysteresis examination had been updated these years constantly. Many researches implicated that low corneal hysteresis involved in pathogenesis and progression of glaucoma which refresh our recognition of the relationship between cornea and glaucoma. This review summarized the characteristics of corneal hysteresis, the examination and the connection with glaucoma to provide the reference for clinical work. (Chin J Ophthalmol, 2017, 53: 140-143) .
NASA Astrophysics Data System (ADS)
Franus, D. V.
2018-05-01
Research is conducted into variation in the stress-strain state of the corneoscleral shell of the human eye under loading by a flat base stamp of varying weight. A three-dimensional finite-element model of the contact problem of loading of the corneoscleral shell in the ANSYS program package is presented. Cornea and sclera are modeled as conjugated transversely isotropic spherical shells. The cornea is modeled as a multilayer shell with variable thickness in which all modeled layers have their own individual elastic properties. The research deals with the numerical calculation of the diameter of the contact zone between the shell and the stamp. Values of correction coefficients for intraocular pressure are obtained depending on the thickness of the corneal shell in its center, allowing the true intraocular pressure to be determined more accurately.
Drowsy driver mobile application: Development of a novel scleral-area detection method.
Mohammad, Faisal; Mahadas, Kausalendra; Hung, George K
2017-10-01
A reliable and practical app for mobile devices was developed to detect driver drowsiness. It consisted of two main components: a Haar cascade classifier, provided by a computer vision framework called OpenCV, for face/eye detection; and a dedicated JAVA software code for image processing that was applied over a masked region circumscribing the eye. A binary threshold was performed over the masked region to provide a quantitative measure of the number of white pixels in the sclera, which represented the state of eye opening. A continuously low white-pixel count would indicate drowsiness, thereby triggering an alarm to alert the driver. This system was successfully implemented on: (1) a static face image, (2) two subjects under laboratory conditions, and (3) a subject in a vehicle environment. Copyright © 2017 Elsevier Ltd. All rights reserved.
Ochronotic Arthropathy: Two Case Reports from a Developing Country
Rathore, Farooq A.; Ayaz, Saeed B.; Mansoor, Sahibzada N.
2016-01-01
Alkaptonuria is a rare inborn error of metabolism, which is classified as an orphan disease. It is due to the lack of an enzyme homogentisate 1,2-dioxygenase, which results in an accumulation of homogentisic acid in different areas of the body, including sclera, skin, cardiac valves, articular cartilage of the large joints and intervertebral disks. We present two cases of alkaptonuria resulting in ochronotic arthropathy with advanced secondary generalized osteoarthritis, intervertebral disk calcifications, skin and scleral pigmentation. In these case reports, both patients had symptoms for >10 years before being diagnosed. Conservative management in the form of high-dose ascorbic acid, exercises, and gait aids was offered to both of them, which resulted in some symptomatic improvement in the first case, while the second case was lost to follow-up. Alkaptonuria is a rare disease, and although it does not clearly impact mortality, early diagnosis may improve the quality of life. PMID:26884684
Ochronotic Arthropathy: Two Case Reports from a Developing Country.
Rathore, Farooq A; Ayaz, Saeed B; Mansoor, Sahibzada N
2016-01-01
Alkaptonuria is a rare inborn error of metabolism, which is classified as an orphan disease. It is due to the lack of an enzyme homogentisate 1,2-dioxygenase, which results in an accumulation of homogentisic acid in different areas of the body, including sclera, skin, cardiac valves, articular cartilage of the large joints and intervertebral disks. We present two cases of alkaptonuria resulting in ochronotic arthropathy with advanced secondary generalized osteoarthritis, intervertebral disk calcifications, skin and scleral pigmentation. In these case reports, both patients had symptoms for >10 years before being diagnosed. Conservative management in the form of high-dose ascorbic acid, exercises, and gait aids was offered to both of them, which resulted in some symptomatic improvement in the first case, while the second case was lost to follow-up. Alkaptonuria is a rare disease, and although it does not clearly impact mortality, early diagnosis may improve the quality of life.
Segmentation of the macular choroid in OCT images acquired at 830nm and 1060nm
NASA Astrophysics Data System (ADS)
Lee, Sieun; Beg, Mirza F.; Sarunic, Marinko V.
2013-06-01
Retinal imaging with optical coherence tomography (OCT) has rapidly advanced in ophthalmic applications with the broad availability of Fourier domain (FD) technology in commercial systems. The high sensitivity afforded by FD-OCT has enabled imaging of the choroid, a layer of blood vessels serving the outer retina. Improved visualization of the choroid and the choroid-sclera boundary has been investigated using techniques such as enhanced depth imaging (EDI), and also with OCT systems operating in the 1060-nm wavelength range. We report on a comparison of imaging the macular choroid with commercial and prototype OCT systems, and present automated 3D segmentation of the choroid-scleral layer using a graph cut algorithm. The thickness of the choroid is an important measurement to investigate for possible correlation with severity, or possibly early diagnosis, of diseases such as age-related macular degeneration.
Light propagation in tissues with controlled optical properties
NASA Astrophysics Data System (ADS)
Tuchin, Valery V.; Maksimova, Irina L.; Zimnyakov, Dmitry A.; Kon, Irina L.; Mavlyutov, Albert H.; Mishin, Alexey A.
1997-10-01
Theoretical and computer modeling approaches, such as Mie theory, radiative transfer theory, diffusion wave correlation spectroscopy, and Monte Carlo simulation were used to analyze tissue optics during a process of optical clearing due to refractive index matching. Continuous wave transmittance and forward scattering measurement as well as intensity correlation experiments were used to monitor tissue structural and optical properties. As a control, tissue samples of the human sclera were taken. Osmotically active solutions, such as Trazograph, glucose, and polyethylene glycol, were used as chemicals. A characteristic time response of human scleral optical clearing the range 3 to 10 min was determined. The diffusion coefficients describing the permeability of the scleral samples to Trazograph were experimentally estimated; the average value was DT approximately equals (0.9 +/- 0.5) X 10-5 cm2/s. The results are general and can be used to describe many other fibrous tissues.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jordan, D.R.; Tse, D.T.; Anderson, R.L.
1990-01-01
Reconstruction of full thickness eyelid defects requires the correction of both posterior lamella (tarsus, conjunctiva) and anterior lamella (skin, muscle). Tarsal substitutes including banked sclera, nasal cartilage, ear cartilage, and periosteum can be beneficial for posterior lamellar repair, while anterior lamellar replacement, including skin grafts, pedicle flaps, advancement flaps, etc., is important to cover the posterior reconstructed portion. At times, due to extensive tissue loss, the eyelid reconstruction can be particularly challenging. We have found an alternative posterior lamellar reconstructive technique utilizing irradiated homologous tarsal plate that can be particularly useful in selected cases of severe tissue loss. The experimentalmore » surgical procedure in monkeys and the histological fate of the implanted tarsus is described in Part I, and followed in Part II by our experience with this tissue in six human patients.« less
Design considerations of a real-time clinical confocal microscope
NASA Astrophysics Data System (ADS)
Masters, Barry R.
1991-06-01
A real-time clinical confocal light microscope provides the ophthalmologist with a new tool for the observation of the cornea and the ocular lens. In addition, the ciliary body, the iris, and the sclera can be observed. The real-time light microscopic images have high contrast and resolution. The transverse resolution is about one half micron and the range resolution is one micron. The following observations were made with visible light: corneal epithelial cells, wing cells, basal cells, Bowman's membrane, nerve fibers, basal lamina, fibroblast nuclei, Descemet's membrane, endothelial cells. Observation of the in situ ocular lens showed lens capsule, lens epithelium, lens fibrils, the interior of lens fibrils. The applications of the confocal microscope include: eye banking, laser refractive surgery, observation of wound healing, observation of the iris, the sciera, the ciliary body, the ocular lens, and the intraocular lens. Digital image processing can produce three-dimensional reconstructions of the cornea and the ocular lens.
Adam, Margaret P; Hennekam, Raoul C M; Keppen, Laura Davis; Bull, Marilyn J; Clericuzio, Carol L; Burke, Leah W; Ormond, Kelly E; Hoyme, Eugene H
2005-08-30
The Marshall-Smith syndrome (MSS) is a distinct malformation syndrome characterized by accelerated skeletal maturation, relative failure to thrive, respiratory difficulties, mental retardation, and unusual facies, including prominent forehead, shallow orbits, blue sclerae, depressed nasal bridge, and micrognathia. At least 33 cases have been reported in the literature, mostly as single case reports or small series. The purpose of the present study is to report on the clinical findings and natural history of MSS in five children and to review the features of three others previously reported, with particular attention to the skeletal and connective tissue findings. Our study demonstrates an increased rate of nontraumatic fractures and other bony and connective tissue abnormalities that support the hypothesis that MSS should be considered an osteochondrodysplasia. In addition, long-term survival beyond infancy is possible if respiratory problems are expectantly and aggressively managed. (c) 2005 Wiley-Liss, Inc.
Optic Nerve Head Biomechanics in Aging and Disease
Downs, J. Crawford
2015-01-01
This nontechnical review is focused upon educating the reader on optic nerve head biomechanics in both aging and disease along two main themes: what is known about how mechanical forces and the resulting deformations are distributed in the posterior pole and ONH (biomechanics) and what is known about how the living system responds to those deformations (mechanobiology). We focus on how ONH responds to IOP elevations as a structural system, insofar as the acute mechanical response of the lamina cribrosa is confounded with the responses of the peripapillary sclera, prelaminar neural tissues, and retrolaminar optic nerve. We discuss the biomechanical basis for IOP-driven changes in connective tissues, blood flow, and cellular responses. We use glaucoma as the primary framework to present the important aspects of ONH biomechanics in aging and disease, as ONH biomechanics, aging, and the posterior pole extracellular matrix (ECM) are thought to be centrally involved in glaucoma susceptibility, onset and progression. PMID:25819451
Miniature LED endoilluminators for vitreoretinal surgery
NASA Astrophysics Data System (ADS)
Hessling, M.; Koelbl, P. S.; Lingenfelder, C.; Koch, F.
2015-07-01
Two innovative approaches for intraocular illumination during vitreoretinal surgery by application of white LEDs are being developed. Both techniques are less harmful to the patient, more convenient for the surgeon and smaller and cheaper compared to conventional illumination by Xenon light sources and optical fibers. These two novel approaches are: I) The miniature LED chandelier endoilluminator consisting of a single white LED with a "light probe" on top of the LED housing that fits in a small incision in the wall of the eye. II) The alternative transscleral LED endoilluminator is integrated into an eye speculum that presses the flat LED top against the eye. The intraocular space is only illuminated by light transmitted through the sclera. In contrast to conventional illumination techniques for vitreoretinal surgery no incision is necessary. Both approaches are evaluated with regard to potential photochemical and thermal risks for the patient's retina and they are tested on porcine eyes.
Ichien, K; Sawada, A; Yamamoto, T; Kitazawa, Y; Shiraki, R; Yoh, M
1999-04-01
Based on our previous report that showed enhanced transfer of mitomycin C to the sclera and the conjunctiva by dissolving the antiproliferative in a reversible thermo-setting gel, we conducted a study to investigate the efficacy of the mitomycin C-gel in the rabbit. We subconjunctivally injected 0.1 ml of the mitomycin C-gel solution containing several amounts of the drug. Trephination was performed in the injected region 24 hours later. Intraocular pressure measurement, and photography and ultrasound biomicroscopic examination of the filtering bleb were done 1, 2, and 4 weeks postoperatively. The gel containing 3.0 micrograms or more mitomycin C significantly enhanced bleb formation in addition to reducing the intraocular pressure. The reversible thermo-setting gel seems to facilitate filtration following glaucoma filtering surgery in the rabbit and deserves further investigation as a new method of mitomycin C application.
The alteration of extraocular muscle arc after hang-back recession in animal experiments.
Lee, J; Kim, S
1996-01-01
We did an animal experimental study to investigate the extraocular muscle arc after hang-back recession on horizontal rectus muscles of five dogs. Two tiny sutures using 8-0 nylon were made on the sclera 8-10 mm posterior to the muscle insertion along the upper and lower margins of the right lateral rectus and left medial rectus to compare the altered muscle arc with the original muscle arc. Hang-back recession was performed on the horizontal rectus muscles and three months later we investigated the change in the muscle arc. Four of the 10 muscles operated showed no change, four were displaced upward (mean +/- SD; 1.00 +/- 0.16 mm) and two were displaced downward (1.00 +/- 0.00 mm). The average displacement was 0.60 +/- 0.52 mm. The alteration of muscle arc after hang-back recession thus seems insignificant.
First-in-Human Trial of a Novel Suprachoroidal Retinal Prosthesis
Ayton, Lauren N.; Blamey, Peter J.; Guymer, Robyn H.; Luu, Chi D.; Nayagam, David A. X.; Sinclair, Nicholas C.; Shivdasani, Mohit N.; Yeoh, Jonathan; McCombe, Mark F.; Briggs, Robert J.; Opie, Nicholas L.; Villalobos, Joel; Dimitrov, Peter N.; Varsamidis, Mary; Petoe, Matthew A.; McCarthy, Chris D.; Walker, Janine G.; Barnes, Nick; Burkitt, Anthony N.; Williams, Chris E.; Shepherd, Robert K.; Allen, Penelope J.
2014-01-01
Retinal visual prostheses (“bionic eyes”) have the potential to restore vision to blind or profoundly vision-impaired patients. The medical bionic technology used to design, manufacture and implant such prostheses is still in its relative infancy, with various technologies and surgical approaches being evaluated. We hypothesised that a suprachoroidal implant location (between the sclera and choroid of the eye) would provide significant surgical and safety benefits for patients, allowing them to maintain preoperative residual vision as well as gaining prosthetic vision input from the device. This report details the first-in-human Phase 1 trial to investigate the use of retinal implants in the suprachoroidal space in three human subjects with end-stage retinitis pigmentosa. The success of the suprachoroidal surgical approach and its associated safety benefits, coupled with twelve-month post-operative efficacy data, holds promise for the field of vision restoration. Trial Registration Clinicaltrials.gov NCT01603576 PMID:25521292
Mudgil, A V; To, K W; Balachandran, R M; Janigian, R H; Tsiaras, W G
1999-01-01
To determine the optimal wavelength for subconjunctival laser suture lysis. 130 black monofilament 10-0 nylon sutures were sewn subconjunctivally into the bare sclera of enucleated rabbit globes. The lowest energy levels facilitating laser suture lysis were determined for the argon green (514.5 NM), argon blue-green (488.0 NM, 514.5 NM), and krypton red (647.1 NM) wavelengths. In addition, absorption spectroscopy was performed on the suture material and conjunctiva using the Perkin Elmer W/VIS Lambda 2 spectrometer. Krypton red produced the fewest buttonhole defects, and it was also the most efficient energy source for suture lysis (P = 0.0001) under nontenectomized conjunctiva. Absorbance spectra studies revealed peak absorbance at 628 NM for the 10-0 nylon suture material. Based on animal and absorption spectroscopy studies, krypton red may be a safer and more efficient wavelength for subconjunctival laser suture lysis.
Gupta, Shikha; Sagar, Pradeep; Gogia, Varun; Khokhar, Sudarshan; Dada, Tanuj
2016-03-01
A young patient presented with visual acuity of hand movements only, unrecordable intraocular pressure, and total cataract after trauma 12 months ago. She reported failure to improve with conservative therapy as well as a direct cycloplexy elsewhere. After cleft localization on preoperative gonioscopy, ultrasound biomicroscopy (UBM), and intraoperative gonioscopy, a partial-thickness scleral flap was fashioned at the site of maximum cleft height. Following phacoaspiration, a multipiece intraocular lens was implanted in the sulcus; its haptics aligned to the axis with maximum height of cyclodialysis. A Cionni ring placed in sulcus was sutured to sclera under the flap to provide additional tamponading effect. Postoperative UBM and gonioscopy confirmed cleft closure. Normalization of intraocular pressure was found on repeated follow-ups till 1 year (12 to 14 mm Hg). UBM showed increase in sulcus diameter, and "double indentation sign" on the ciliary body.
A Correlation Between Changes in Solar Luminosity and Differential Radius Measurements
NASA Technical Reports Server (NTRS)
Kroll, R. J.; Hill, H. A.; Beardsley, B. J.
1990-01-01
Solar luminosity variations occurring during solar cycle 21 can be attributed in large part to the presence of sunspots and faculae. Nevertheless, there remains a residual portion of the luminosity variation distinctly unaccounted for by these phenomena of solar activity. At the Santa Catalina Laboratory for Experimental Relativity by Astrometry (SCLERA), observations of the solar limb are capable of detecting changes in the solar limb darkening function by monitoring a quantity known as the differential radius. These observations are utilized in such a way that the effects of solar activity are minimized in order to reveal the more fundamental structure of the photosphere. The results of observations made during solar cycle 21 at various solar latitudes indicate that a measurable change did occur in the global photospheric limb darkening function. It is proposed that the residual luminosity change is associated in part with this change in limb darkening.
Osteogenesis imperfecta in childhood: treatment strategies.
Engelbert, R H; Pruijs, H E; Beemer, F A; Helders, P J
1998-12-01
Osteogenesis imperfecta (OI) is a skeletal disorder of remarkable clinical variability characterized by bone fragility, osteopenia, variable degrees of short stature, and progressive skeletal deformities. Additional clinical manifestations such as blue sclerae, dentinogenesis imperfecta, joint laxity, and maturity onset deafness are described in the literature. OI occurs in about 1 in 20,000 births and is caused by quantitative and qualitative defects in the synthesis of collagen I. Depending on the severity of the disease, a large impact on motor development, range of joint motion, muscle strength, and functional ability may occur. Treatment strategies should primarily focus on the improvement of functional ability and the adoption of compensatory strategies, rather than merely improving range of joint motion and muscle strength. Surgical treatment of the extremities may be indicated to stabilize the long bones to optimize functional ability and walking capacity. Surgical treatment of the spine may be indicated in patients with progressive spinal deformity and in those with symptomatic basilar impression.
Surgically Induced Scleral Necrosis in a Patient With Rheumatoid Arthritis After AGV Implantation.
Kumar, Suresh; Ichhpujani, Parul; Thakur, Sahil
2018-03-01
Surgically induced scleral necrosis (SINS) is a rare entity that has till date not been reported in a patient of glaucoma undergoing Ahmed glaucoma valve (AGV) implantation. We present a case of primary open-angle glaucoma who underwent AGV implantation followed by development of scleral necrosis, involving both the scleral patch graft and host sclera. After failure of surgical and medical management, AGV had to be explanted. The patient was diagnosed with rheumatoid arthritis and had to be treated with steroids and azathioprine for the same. SINS is a potentially disastrous complication of ocular surgery that can occur in patients with systemic diseases like rheumatoid arthritis and requires aggressive management to salvage the eye. SINS can occur with AGV implantation. Treatment may require aggressive medical and surgical intervention. It is imperative to evaluate patients for systemic illness before planning an AGV implant.
Bernstein, P S; Khachik, F; Carvalho, L S; Muir, G J; Zhao, D Y; Katz, N B
2001-03-01
There is increasing evidence that the macular pigment carotenoids, lutein and zeaxanthin, may play an important role in the prevention of age-related macular degeneration, cataract, and other blinding disorders. Although it is well known that the retina and lens are enriched in these carotenoids, relatively little is known about carotenoid levels in the uveal tract and in other ocular tissues. Also, the oxidative metabolism and physiological functions of the ocular carotenoids are not fully understood. Thus, we have set out to identify and quantify the complete spectrum of dietary carotenoids and their oxidative metabolites in a systematic manner in all tissues of the human eye in order to gain better insight into their ocular physiology. Human donor eyes were dissected, and carotenoid extracts from ocular tissues [retinal pigment epithelium/choroid (RPE/choroid), macula, peripheral retina, ciliary body, iris, lens, vitreous, cornea, and sclera] were analysed by high-performance liquid chromatography (HPLC). Carotenoids were identified and quantified by comparing their chromatographic and spectral profiles with those of authentic standards. Nearly all ocular structures examined with the exception of vitreous, cornea, and sclera had quantifiable levels of dietary (3R,3'R,6'R)-lutein, zeaxanthin, their geometrical (E / Z) isomers, as well as their metabolites, (3R,3'S,6'R)-lutein (3'-epilutein) and 3-hydroxy-beta,epsilon-caroten-3'-one. In addition, human ciliary body revealed the presence of monohydroxycarotenoids and hydrocarbon carotenoids, while only the latter group was detected in human RPE/choroid. Uveal structures (iris, ciliary body, and RPE/choroid) account for approximately 50% of the eye's total carotenoids and approximately 30% of the lutein and zeaxanthin. In the iris, these pigments are likely to play a role in filtering out phototoxic short-wavelength visible light, while they are more likely to act as antioxidants in the ciliary body. Both mechanisms, light screening and antioxidant, may be operative in the RPE/choroid in addition to a possible function of this tissue in the transport of dihydroxycarotenoids from the circulating blood to the retina. This report lends further support for the critical role of lutein, zeaxanthin, and other ocular carotenoids in protecting the eye from light-induced oxidative damage and aging. Copyright 2001 Academic Press.
Protective effect of 4-coumaric acid from UVB ray damage in the rabbit eye.
Lodovici, Maura; Caldini, Silvia; Morbidelli, Lucia; Akpan, Victor; Ziche, Marina; Dolara, Piero
2009-01-08
UV-induced oxidation damage seems to play a major role in a number of specific pathological conditions of intraocular tissues, such as cataract formation and retinal degeneration. Therefore, antioxidant and/or scavenger compounds might protect the eyes from UV-induced cellular damage. We previously reported that 4-coumaric acid (4-CA) is able to protect rabbit corneal-derived cells (SIRC) from UVB-induced oxidation damage. In this study we evaluated the protective effect of 4-CA against UVB-induced cell damage in rabbit cornea in vivo. Twelve male New Zealand albino rabbits were used; four rabbits were used as a control and received vehicle in one eye and 4-CA acid in the contralateral eye; eight rabbits were exposed to UVB rays (79.2mJ/cm(2)) and three days before to UV exposure each animal received 1 drop/day of vehicle in one eye and 1 drop/day of vehicle containing 4-CA (164ng) in the contralateral eye. Corneal and sclera tissues were removed and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) levels were measured. Superoxide dismutase (SOD) and xanthine oxidase (XO) activities were determined in aqueous humour. UVB-induced vessel hyper-reactivity was strongly reduced at 4 and 24h after UVB exposure after local treatment with 4-CA, 8-oxodGuo levels, a marker of oxidative DNA damage, were significantly increased (P<0.05) in sclera and cornea by UVB irradiation, but when 4-CA was administered to the conjunctiva in a buffered solution once a day for 3d before and 6d after UVB exposure, levels of 8-oxodGuo were similar to controls and significantly reduced (P<0.05) compared to UVB-treated corneas. XO activity in the aqueous humour was significantly increased. The administration of 4-CA for 3d before and 6d after UVB irradiation induced a small but significant (P<0.05) reduction of XO compared with control eyes. Our results indicate that the administration of 4-CA protects eye tissues, thus reducing the harmful effect of UVB radiation at low concentration, probably through its free radical scavenging and antioxidant properties. Therefore, 4-CA may be useful in protecting the eye from free radical damage following UVB exposure from sunlight, UV lamps and welding torches.
Parekh, Mohit; Ferrari, Stefano; Di Iorio, Enzo; Barbaro, Vanessa; Camposampiero, Davide; Karali, Marianthi; Ponzin, Diego; Salvalaio, Gianni
2012-06-12
Enucleation is the process of retrieving the ocular globe from a cadaveric donor leaving the rest of the globe undisturbed. Excision refers to the retrieval of ocular tissues, especially cornea, by cutting it separate from the ocular globe. Evisceration is the process of removing the internal organs referred here as retina. The ocular globe consists of the cornea, the sclera, the vitreous body, the lens, the iris, the retina, the choroid, muscles etc (Suppl. Figure 1). When a patient is suffering from corneal damage, the cornea needs to be removed and a healthy one must be transplanted by keratoplastic surgeries. Genetic disorders or defects in retinal function can compromise vision. Human ocular globes can be used for various surgical procedures such as eye banking, transplantation of human cornea or sclera and research on ocular tissues. However, there is little information available on human corneal and retinal excision, probably due to the limited accessibility to human tissues. Most of the studies describing similar procedures are performed on animal models. Research scientists rely on the availability of properly dissected and well-conserved ocular tissues in order to extend the knowledge on human eye development, homeostasis and function. As we receive high amount of ocular globes out of which approximately 40% (Table 1) of them are used for research purposes, we are able to perform huge amount of experiments on these tissues, defining techniques to excise and preserve them regularly. The cornea is an avascular tissue which enables the transmission of light onto the retina and for this purpose should always maintain a good degree of transparency. Within the cornea, the limbus region, which is a reservoir of the stem cells, helps the reconstruction of epithelial cells and restricts the overgrowth of the conjunctiva maintaining corneal transparency and clarity. The size and thickness of the cornea are critical for clear vision, as changes in either of them could lead to distracted, unclear vision. The cornea comprises of 5 layers; a) epithelium, b) Bowman's layer, c) stroma, d) Descemet's membrane and e) endothelium. All layers should function properly to ensure clear vision(4,5,6). The choroid is the intermediate tunic between the sclera and retina, bounded on the interior by the Bruch's membrane and is responsible for blood flow in the eye. The choroid also helps to regulate the temperature and supplies nourishment to the outer layers of the retina(5,6). The retina is a layer of nervous tissue that covers the back of the ocular globe (Suppl. Figure 1) and consists of two parts: a photoreceptive part and a non-receptive part. The retina helps to receive the light from the cornea and lens and converts it into the chemical energy eventually transmitted to the brain with help of the optic nerve(5,6). The aim of this paper is to provide a protocol for the dissection of corneal and retinal tissues from human ocular globes. Avoiding cross-contamination with adjacent tissues and preserving RNA integrity is of fundamental importance as such tissues are indispensable for research purposes aimed at (i) characterizing the transcriptome of the ocular tissues, (ii) isolating stem cells for regenerative medicine projects, and (iii) evaluating histological differences between tissues from normal/affected subjects. In this paper we describe the technique we currently use to remove the cornea, the choroid and retinal tissues from an ocular globe. Here we provide a detailed protocol for the dissection of the human ocular globe and the excision of corneal and retinal tissues. The accompanying video will help researchers to learn an appropriate technique for the retrieval of precious human tissues which are difficult to find regularly.
Yuce, E; Yildirim, N; Yildirim, N C; Paksoy, M Y; Bagci, E
2014-06-15
The essential oil composition and in vitro antioxidant and antifungal activity of the Salvia sclarea L. from Munzur Valley in Tunceli, Turkey were evaluated in this research. The in vitro antifungal activity of ethanol, hexane and aqueous extracts of S. sclarea against pathogen fungi Epicoccum nigrum and Colletotrichum coccodes were investigated. The essential oil of aerial parts of S. sclarea was obtained by hydrodistillation and was analysed by GC and GC—MS. Total antioxidant status was determined by using Rel assay diagnostics TAS assay kit (Lot.RL024) by Multiscan FC (Thermo). 33 compounds were identified representing the 85.0% of the total oil. The most abundant components (>5%) of the S. sclarea essential oils were caryophyllene oxide (24.1%), sclareol (11.5%), spathulenol (11.4%), 1H-naphtho (2,1,6) pyran (8.6%) and b—caryophyllene (5.1%). The best antifungal and antioxidant effect was seen in ethanolic S. sclarea extract. It can be said that Salvia sclerae could be used as natural antioxidant.
Goiato, Marcelo Coelho; Santos, Daniela Micheline dos; Souza, Josiene Firmino; Moreno, Amália; Pesqueira, Aldiéris Alves
2010-12-01
Esthetics and durability of materials used to fabricate artificial eyes has been an important issue since artificial eyes are essential to restore esthetics and function, protect the remaining tissues and help with patients' psychological therapy. However, these materials are submitted to degrading effects of environmental agents on the physical properties of the acrylic resin. This study assessed the color stability of acrylic resins used to fabricate sclera in three basic shades (N1, N2 and N3) when subjected to accelerated aging, mechanical and chemical polishing. Specimens of each resin were fabricated and submitted to mechanical and chemical polishing. Chromatic analysis was performed before and after accelerated aging through ultraviolet reflection spectrophotometry. All specimens revealed color alteration following polishing and accelerated aging. The resins presented statistically significant chromatic alteration (p<0.01) between the periods of 252 and 1008 h. Both polishing methods presented no significant difference between the values of color derivatives of resins.
Glucose Transporters are Abundant in Cells with "Occluding" Junctions at the Blood-Eye Barriers
NASA Astrophysics Data System (ADS)
Harik, Sami I.; Kalaria, Rajesh N.; Whitney, Paul M.; Andersson, Lars; Lundahl, Per; Ledbetter, Steven R.; Perry, George
1990-06-01
We studied the distribution of the "erythroid/brain" glucose transporter protein in the human and rat eye by immunocytochemistry with monoclonal and polyclonal antibodies to the C terminus of the human erythrocyte glucose transporter. We found intense immunocytochemical staining in the endothelium of microvessels of the retina, optic nerve, and iris but not in microvessels of the choroid, ciliary body, sclera, and other retro-orbital tissues. In addition, we found marked immunocytochemical staining of retinal pigment epithelium, ciliary body epithelium, and posterior epithelium of the iris. The common feature of all those endothelial and epithelial cells that stained intensely for the glucose transporter is the presence of "occluding" intercellular junctions, which constitute the anatomical bases of the blood-eye barriers. We propose that a high density of the glucose transporter is a biochemical concomitant of epithelial and endothelial cells with barrier characteristics, at least in tissues that have a high metabolic requirement for glucose.
Linkage mapping of the primary disease locus for collie eye anomaly.
Lowe, Jennifer K; Kukekova, Anna V; Kirkness, Ewen F; Langlois, Mariela C; Aguirre, Gustavo D; Acland, Gregory M; Ostrander, Elaine A
2003-07-01
Collie eye anomaly (cea) is a hereditary ocular disorder affecting development of the choroid and sclera segregating in several breeds of dog, including rough, smooth, and Border collies and Australian shepherds. The disease is reminiscent of the choroidal hypoplasia phenotype observed in humans in conjunction with craniofacial or renal abnormalities. In dogs, however, the clinical phenotype can vary significantly; many dogs exhibit no obvious clinical consequences and retain apparently normal vision throughout life, while severely affected animals develop secondary retinal detachment, intraocular hemorrhage, and blindness. We report genetic studies establishing that the primary cea phenotype, choroidal hypoplasia, segregates as an autosomal recessive trait with nearly 100% penetrance. We further report linkage mapping of the primary cea locus to a 3.9-cM region of canine chromosome 37 (LOD = 22.17 at theta = 0.076), in a region corresponding to human chromosome 2q35. These results suggest the presence of a developmental regulatory gene important in ocular embryogenesis, with potential implications for other disorders of ocular vascularization.
Tedja, Milly S; Wojciechowski, Robert; Hysi, Pirro G; Eriksson, Nicholas; Furlotte, Nicholas A; Verhoeven, Virginie J M; Iglesias, Adriana I; Meester-Smoor, Magda A; Tompson, Stuart W; Fan, Qiao; Khawaja, Anthony P; Cheng, Ching-Yu; Höhn, René; Yamashiro, Kenji; Wenocur, Adam; Grazal, Clare; Haller, Toomas; Metspalu, Andres; Wedenoja, Juho; Jonas, Jost B; Wang, Ya Xing; Xie, Jing; Mitchell, Paul; Foster, Paul J; Klein, Barbara E K; Klein, Ronald; Paterson, Andrew D; Hosseini, S Mohsen; Shah, Rupal L; Williams, Cathy; Teo, Yik Ying; Tham, Yih Chung; Gupta, Preeti; Zhao, Wanting; Shi, Yuan; Saw, Woei-Yuh; Tai, E-Shyong; Sim, Xue Ling; Huffman, Jennifer E; Polašek, Ozren; Hayward, Caroline; Bencic, Goran; Rudan, Igor; Wilson, James F; Joshi, Peter K; Tsujikawa, Akitaka; Matsuda, Fumihiko; Whisenhunt, Kristina N; Zeller, Tanja; van der Spek, Peter J; Haak, Roxanna; Meijers-Heijboer, Hanne; van Leeuwen, Elisabeth M; Iyengar, Sudha K; Lass, Jonathan H; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G; Vingerling, Johannes R; Lehtimäki, Terho; Raitakari, Olli T; Biino, Ginevra; Concas, Maria Pina; Schwantes-An, Tae-Hwi; Igo, Robert P; Cuellar-Partida, Gabriel; Martin, Nicholas G; Craig, Jamie E; Gharahkhani, Puya; Williams, Katie M; Nag, Abhishek; Rahi, Jugnoo S; Cumberland, Phillippa M; Delcourt, Cécile; Bellenguez, Céline; Ried, Janina S; Bergen, Arthur A; Meitinger, Thomas; Gieger, Christian; Wong, Tien Yin; Hewitt, Alex W; Mackey, David A; Simpson, Claire L; Pfeiffer, Norbert; Pärssinen, Olavi; Baird, Paul N; Vitart, Veronique; Amin, Najaf; van Duijn, Cornelia M; Bailey-Wilson, Joan E; Young, Terri L; Saw, Seang-Mei; Stambolian, Dwight; MacGregor, Stuart; Guggenheim, Jeremy A; Tung, Joyce Y; Hammond, Christopher J; Klaver, Caroline C W
2018-06-01
Refractive errors, including myopia, are the most frequent eye disorders worldwide and an increasingly common cause of blindness. This genome-wide association meta-analysis in 160,420 participants and replication in 95,505 participants increased the number of established independent signals from 37 to 161 and showed high genetic correlation between Europeans and Asians (>0.78). Expression experiments and comprehensive in silico analyses identified retinal cell physiology and light processing as prominent mechanisms, and also identified functional contributions to refractive-error development in all cell types of the neurosensory retina, retinal pigment epithelium, vascular endothelium and extracellular matrix. Newly identified genes implicate novel mechanisms such as rod-and-cone bipolar synaptic neurotransmission, anterior-segment morphology and angiogenesis. Thirty-one loci resided in or near regions transcribing small RNAs, thus suggesting a role for post-transcriptional regulation. Our results support the notion that refractive errors are caused by a light-dependent retina-to-sclera signaling cascade and delineate potential pathobiological molecular drivers.
Optic nerve head biomechanics in aging and disease.
Downs, J Crawford
2015-04-01
This nontechnical review is focused upon educating the reader on optic nerve head biomechanics in both aging and disease along two main themes: what is known about how mechanical forces and the resulting deformations are distributed in the posterior pole and ONH (biomechanics) and what is known about how the living system responds to those deformations (mechanobiology). We focus on how ONH responds to IOP elevations as a structural system, insofar as the acute mechanical response of the lamina cribrosa is confounded with the responses of the peripapillary sclera, prelaminar neural tissues, and retrolaminar optic nerve. We discuss the biomechanical basis for IOP-driven changes in connective tissues, blood flow, and cellular responses. We use glaucoma as the primary framework to present the important aspects of ONH biomechanics in aging and disease, as ONH biomechanics, aging, and the posterior pole extracellular matrix (ECM) are thought to be centrally involved in glaucoma susceptibility, onset and progression. Copyright © 2015 Elsevier Ltd. All rights reserved.
Painless Jaundice Caused by Clonorchis sinensis Infection: A Case Report.
Hao, Yuhua; Bao, Wanguo; Jin, Meishan; Li, Yuxiang; Wang, Feng
2016-06-01
A man with only yellowing of the skin and eye sclera was diagnosed with clonorchiasis, which rarely manifested jaundice as the initial symptom. However, because of a lack of evidence for a diagnostic gold standard, the time until definitive diagnosis was more than a week. The diagnostic process relied on inquiring about the patient's history, including the place of residence, dietary habits, and symptoms, as well as on serological findings, an imaging examination, and pathological findings. MRCP and CT results showed mild dilatation of intrahepatic ducts and increased periductal echogenicity. The eggs were ultimately found in stool by water sedimentation method after the negative report through direct smear. DNA sequencing of PCR production of the eggs demonstrated 98-100% homology with ITS2 of Clonorchis sinensis. After anti-parasite medical treatment, the patient's symptoms were gradually relieved. Throughout the diagnostic procedure, besides routine examinations, the sedimentation method or concentration method could be used as a sensitive way for both light and heavy C. sinensis infection in the definite diagnosis.
6-Hydroxy dopamine does not affect lens-induced refractive errors but suppresses deprivation myopia.
Schaeffel, F; Hagel, G; Bartmann, M; Kohler, K; Zrenner, E
1994-01-01
Degradation of the retinal image by translucent occluders during postnatal development induces axial myopia in chickens, tree shrews and monkeys. Local visual deprivation produces myopia even in local regions of the eye and neither accommodation nor intact connection between the eye and the brain are necessary. Therefore, it is an important question whether a similar local-retinal pathway translating visual information into growth or stretch signals to the underlying sclera is acting to emmetropize the growing eye. It is not known until now whether occluder deprivation triggers similar eye growth (or scleral stretch) mechanisms that are also responsible for visual guidance of normal refractive development. We here report that, in chickens, 6-hydroxy dopamine suppresses deprivation-induced myopia but has no effect on the magnitude of changes in axial eye elongation that are induced by spectacle lenses. The result suggests that, in chickens with normal accommodation, two pharmacologically different feedback loops may be responsible for deprivation myopia and lens-induced refractive errors.
[Miyake-Apple video analysis of movement patterns of an accommodative intraocular lens implant].
Auffarth, G U; Schmidbauer, J; Becker, K A; Rabsilber, T M; Apple, D J
2002-11-01
The potentially accommodative intraocular lens (IOL) is a new development in IOL design We evaluated the new Humanoptics 1CU accommodative IOL in a laboratory study with human post mortem autopsy eyes. Using the Miyake-Apple posterior view video technique, the movement pattern of the IOL was tested and observed from the posterior perspective. RESULTS. A circular bend at the level of the ciliary body applied slight circular force onto the sclera allowing the relaxation of the zonules. The shift of focus was demonstrated by using a reading target. In addition, viscoelastic was injected into the vitreous resulting in the same anterior movement of the IOL optic. The 1CU Humanoptics accommodative IOL showed potential accommodative behaviour in the laboratory. The accommodative (respectively pseudoaccommodative) effect was based on the anterior shift principle with anterior movement of the IOL-optic in the state of relaxing zonules. Whether this reflects the clinical situation, especially to this extent, must be further evaluated.
Analysis of the scattering performance of human retinal tissue layers
NASA Astrophysics Data System (ADS)
Zhu, Dan; Gao, Zhisan; Ye, Haishui; Yuan, Qun
2017-02-01
Human retina is different from other ocular tissues, such as cornea, crystalline lens and vitreous because of high scattering performance. As an anisotropic tissue, we cannot neglect its impact on the polarization state of the scattered light. In this paper, Mie scattering and radiative transfer theory are applied to analyze the polarization state of backscattered light from four types of retinal tissues, including neural retina, retinal pigment epithelial (RPE), choroid and sclera. The results show that the most backscattered zones in different depths have almost the same electrical fields of Jones vector, which represents the polarization state of light, whether neural retina layer is under normal incidence or oblique incidence. Very little change occurs in the polarization of backscattered light compared to that of the incident light. Polarization distribution of backward scattered light from neural retina layer doesn't make apparent effects on polarization phase shifting in spectral domain OCT because its thickness is far less than photon mean free path, while other retinal tissues do not meet this rule.
Morphology of the eyeball from the Humpback whale (Megaptera novaeangliae).
Rodrigues, Fernanda M; Silva, Fernanda M O; Trompieri-Silveira, Ana Carolina; Vergara-Parente, Jociery E; Miglino, Maria Angélica; Guimarães, Juliana P
2014-05-01
Aquatic mammals underwent morphological and physiological adaptations due to the transition from terrestrial to aquatic environment. One of the morphological changes regards their vision since cetaceans' eyes are able to withstand mechanical, chemical, osmotic, and optical water conditions. Due to insufficient information about these animals, especially regarding their sense organs, this study aimed to describe the morphology of the Humpback whale (Megaptera novaeangliae) eyeball. Three newborn females, stranded dead on the coast of Sergipe and Bahia, Brazil, were used. Samples were fixed in a 10% formalin solution, dissected, photographed, collected, and evaluated through light and electron microscopy techniques. The Humpback whale sclera was thick and had an irregular surface with mechanoreceptors in its lamina propria. Lens was dense, transparent, and ellipsoidal, consisting of three layers, and the vascularized choroid contains melanocytes, mechanoreceptors, and a fibrous tapetum lucidum. The Humpback whale eyeball is similar to other cetaceans and suggests an adaptation to diving and migration, contributing to the perception of differences in temperature, pressure, and lighting. Copyright © 2014 Wiley Periodicals, Inc.
Hearing Loss in Osteogenesis Imperfecta: Characteristics and Treatment Considerations
Pillion, Joseph P.; Vernick, David; Shapiro, Jay
2011-01-01
Osteogenesis imperfecta (OI) is the most common heritable disorder of connective tissue. It is associated with fractures following relatively minor injury, blue sclerae, dentinogenesis imperfecta, increased joint mobility, short stature, and hearing loss. Structures in the otic capsule and inner ear share in the histologic features common to other skeletal tissues. OI is due to mutations involving several genes, the most commonly involved are the COL1A1 or COL1A2 genes which are responsible for the synthesis of the proalpha-1 and proalpha-2 polypeptide chains that form the type I collagen triple helix. A genotype/phenotype relationship to hearing loss has not been established in OI. Hearing loss is commonly found in OI with prevalence rates ranging from 50 to 92% in some studies. Hearing loss in OI may be conductive, mixed, or sensorineural and is more common by the second or third decade. Treatment options such as hearing aids, stapes surgery, and cochlear implants are discussed. PMID:22567374
Advances in the Classification and Treatment of Osteogenesis Imperfecta.
Thomas, Inas H; DiMeglio, Linda A
2016-02-01
Osteogenesis imperfecta (OI) is a rare disorder of type 1 collagen with 13 currently identified types attributable to inherited abnormalities in type 1 collagen amount, structure, or processing. The disease is characterized by an increased susceptibility to bony fracture. In addition to the skeletal phenotype, common additional extraskeletal manifestations include blue sclerae, dentinogenesis imperfecta, vascular fragility, and hearing loss. Medical management is focused on minimizing the morbidity of fractures, pain, and bone deformities by maximizing bone health. Along with optimizing Vitamin D status and calcium intake and physical/occupational therapy, individualized surgical treatment may be indicated. Pharmacological therapy with bisphosphonate medications is now routinely utilized for moderate to severe forms and appears to have a good safety profile and bone health benefits. New therapies with other anti-resorptives as well as anabolic agents and transforming growth factor (TGF)β antibodies are in development. Other potential treatment modalities could include gene therapy or mesenchymal cell transplant. In the future, treatment choices will be further individualized in order to reduce disease morbidity and mortality.
[Dry transconjunctival sutureless 25-gauge vitrectomy in the treatment of pediatric cataract].
You, Cai-yun; Xie, Li-xin
2009-08-01
Posterior capsule opacification is the most frequent complication of pediatric cataract surgery. To prevent posterior capsule opacification, primary phacoemulsification, posterior capsulotomy and anterior vitrectomy with intraocular lens implantation is the preferred method in the treatment of pediatric cataract. Anterior vitrectomy cutter, with 18-gauge, maximum frequency at 600/min and has simultaneous cutting, irrigation and aspiration functions, is associated with more complications and poor outcomes. In 20-gauge surgery, pars plana vitrectomy is performed with two-port sclerotomy. The irrigation increases movement of vitreous and 20-gauge sclerotomy needs suture for closing. In 25-gauge surgery, the vitreous cutter can be introduced into the vitreous cavity directly though conjunctiva and sclera. The stab incision is roughly half the size of 20-gauge cutter, therefore, the sclerotomy incision can be left unsutured. Surgery with dry transconjunctival sutureless 25-gauge vitrectomy may decrease the requirement for secondary membrane surgery and the risk for retinal detachment. The application of dry transconjunctival sutureless 25-gauge vitrectomy in the treatment of pediatric cataract is reviewed.
Metastatic iridociliary adenocarcinoma in a labrador retriever.
Zarfoss, M K; Dubielzig, R R
2007-09-01
An enucleated left eye from a 15-year-old female spayed Labrador Retriever was received by the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) for histopathologic evaluation. Routine histologic preparation included staining with hematoxylin and eosin, and with alcian blue periodic acid-Schiff (PAS). At necropsy 9 months later, all grossly abnormal tissues (ipsilateral orbit and lung) were submitted to the COPLOW for histopathologic evaluation. Histopathologic evaluation of the globe revealed extensive invasion of the uvea and sclera by a pleomorphic cell population that formed disorganized cords and exhibited PAS-positive basement membrane material. Necropsy revealed a morphologically similar tumor in the ipsilateral orbit and lung. On immunohistochemical examination, the intraocular tumor stained diffusely immunopositive for vimentin, S-100, and neuron-specific enolase and multifocally, sparsely immunopositive for cytokeratin AE1/AE3. The orbital and thoracic tumors stained positively for vimentin but negatively for cytokeratin AE1/AE3. There are few reports of canine metastatic iridociliary adenocarcinoma in the literature; this is the first with immunohistochemical analysis.
NASA Astrophysics Data System (ADS)
Ambekar Ramachandra Rao, Raghu
Collagen is the most abundant structural protein found in the human body, and is responsible for providing structure and function to tissues. Collagen molecules organize naturally into structures called fibers on the scale of the wavelength of light and lack inversion symmetry, thus allowing for the process of second harmonic generation (SHG) when exposed to intense incident light. We have developed two quantitative techniques: Fourier transform-second-harmonic generation (FT-SHG) imaging and generalized chi2 second-harmonic generation (chi2-SHG) imaging. In order to show that FT-SHG imaging can be used as a valuable diagnostic tool for real-world biological problems, we first investigate collagenase-induced injury in horse tendons. Clear differences in collagen fiber organization between normal and injured tendon are quantified. In particular, we observe that the regularly oriented organization of collagen fibers in normal tendons is disrupted in injured tendons leading to a more random organization. We also observe that FT-SHG microscopy is more sensitive in assessing tendon injury compared to the conventional polarized light microscopy. The second study includes quantifying collagen fibers in cortical bone using FT-SHG imaging and comparing it with scanning electron microscopy (SEM). Further, as an example study, we show how FT-SHG imaging could be used to quantify changes in bone structure as a function of age. Some initial work and future directions for extending FT-SHG to 3D are also discussed. The second technique, chi2-SHG imaging, takes advantage of the coherent nature of SHG and utilizes polarization to extract the second-order susceptibility (d elements) which provides information on molecular organization, i.e., it provides access to sub-diffractional changes "optically". We use chi2-SHG in combination with FT-SHG imaging to investigate a couple of biological problems. First, we quantify differences in collagen fiber organization between cornea and sclera of the eye in order to investigate their properties of transparency and opacity, respectively. We find from chi2-SHG imaging that there is no statistical difference in the values of d elements between cornea and sclera, indicating that the underlying collagen structure generating SHG from the two is similar at the level of detection of SHG microscopy. However, the difference lies in the spatial organization of these collagen fibers as observed from FT-SHG imaging. We find that cornea contains lamellae with patches of ordered and uniform diameter collagen fibers with axial order, which could be the reason for its transparent behavior. Conversely, there are no lamellae in sclera (i.e., no axial order), and fibers are thicker, denser, have inconsistent diameters, and possess relatively inhomogeneous orientations, leading to its opaque nature. We also utilized the two techniques to assess differences in stromal collagen fibers for several human breast tissue conditions: normal, hyperplasia, dysplasia, and malignant. Using FT-SHG imaging, we note differences between malignant and other pathological conditions through the metric A.I. ratio. Using generalized chi2-SHG imaging, we observe structural changes in collagen at the molecular scale, and a particular d element showed a more sensitive differentiation between breast tissue conditions, except between hyperplasia and normal/dysplasia. We also find that the trigonal symmetry (3m) is a more appropriate model to describe collagen fibers in malignant tissues as opposed to the conventionally used hexagonal symmetry (C6). Furthermore, the percentage of abnormal collagen fibers could potentially be used as a metric for differentiating breast tissue conditions. We also introduce a technique for extending chi2-SHG to fibers with curvature which is useful for generating chi2-image maps (in terms of d elements) instead of the conventional SHG intensity images. The spatial variations in d elements will provide additional information. For example, in breast cancer tissues, it may help in observing how fibers change from normal to malignant spatially, especially around region of cancerous cells. Finally, we discuss some of the interesting immediate and later future work of quantitative SHG imaging we aim to carry out in our lab. (Abstract shortened by UMI.)
Characterization of silver nanoparticle-infused tissue adhesive for ophthalmic use.
Yee, William; Selvaduray, Guna; Hawkins, Benjamin
2015-03-01
In this work, we demonstrate the successful enhancement of breaking strength, adhesive strength, and antibacterial efficacy of ophthalmic tissue adhesive (2-octyl cyanoacrylate) by doping with silver nanoparticles, and investigate the effects of nanoparticle size and concentration. Recent work has shown that silver nanoparticles are a viable antibacterial additive to many compounds, but their efficacy in tissue adhesives was heretofore untested. Our results indicate that doping the adhesive with silver nanoparticles reduced bacterial growth by an order of magnitude or more; nanoparticle size and concentration had minimal influence in the range tested. Tensile breaking strength of polymerized adhesive samples and adhesive strength between a T-shaped support and excised porcine sclera were measured using a universal testing machine according to ASTM (formerly American Society for Testing and Materials) standard techniques. Both tests showed significant improvement with the addition of silver nanoparticles. The enhanced mechanical strength and antibacterial efficacy of the doped adhesive supports the use of tissue adhesives as a viable supplement or alternative to sutures. Copyright © 2015 Elsevier Ltd. All rights reserved.
Takkar, Brijesh; Azad, Rajvardhan; Azad, Shorya; Rathi, Anubha
2015-01-01
AIM To describe a new surgical technique for managing dislocated sclerotic cataractous lens. METHODS Six patients with advanced posteriorly dislocated cataracts were operated at a tertiary care centre and analyzed retrospectively. After standard 3 port 23 G pars plana vitrectomy and perfluorocarbon liquid (PFCL) injection, the dislocated white cataract was held with occlusion using phaco fragmatome and then chopped into smaller pieces with a sharp tipped chopper using 25 G chandelier endoilluminator. Each piece was emulsified individually. Following aspiration of PFCL, Fluid Air Exchange was done in all the cases and surgery completed uneventfully. RESULTS Best corrected visual acuity (BCVA) in all the patients was better than 6/12 after one month of follow up. No serious complications were noted till minimum 6mo of follow up. CONCLUSION Four port posterior segment nucleotomy with a chandelier endoilluminator, fragmatome and a chopper appears to be a safe, easy and effective procedure for managing dislocated sclerotic cataractous nuclei. Ultrasonic energy used and adverse thermal effects of the fragmatome on the sclera may be lesser. PMID:26309887
Imaging of trabecular meshwork using Bessel-Gauss light sheet with fluorescence
NASA Astrophysics Data System (ADS)
Jie Jeesmond Hong, Xun; Shinoj, V. K.; Murukeshan, V. M.; Baskaran, M.; Aung, Tin
2017-03-01
Ocular imaging technology that holds promise for both fundamental investigation and clinical detection of glaucoma is still a challenging research area. A direct view of the trabecular meshwork (TM) with high resolution is not generally possible because the iridocorneal angle region is obstructed by the sclera overlap. The best approach to observe the aqueous outflow system (AOS) is therefore to view from the opposite angle. In this research work, we developed two imaging systems for the high resolution ex vivo studies of the AOS inside porcine eye, based on a Gaussian illuminated and a digitally scanned Bessel-Gauss beam light sheet fluorescence configurations. The digitally scanned Bessel-Gauss beam is able to overcome the trade-off between the length and thickness of the Gaussian light sheet to give better imaging performance. It has adequate spatial resolution to resolve critical anatomical structures such as the TM, thereby enabling objective information about the AOS. This non-contact and non-invasive imaging methodology with excellent safety profile is expected to be well received by vision researchers and clinicians in the evaluation and management of glaucoma.
Larrosa, Mar; Lodovici, Maura; Morbidelli, Lucia; Dolara, Piero
2008-10-01
This paper studied the effect on UV-B ocular damage of 10microM hydrocaffeic acid (HCAF) alone and as a mixture (MIX) (5 microM HCAF+5 microM p-coumaric acid). Since ocular UV-B damage is mediated by reactive oxygen species, the aim was to test if HCAF and MIX could reduce oxidation damage in human conjunctival cells (WKD) in vitro and in cornea and sclera of rabbits in vivo. After UVB irradiation (44 J/m(2)) of WKD cells, 8-oxodG levels in DNA were markedly increased and this effect was attenuated by HCAF and MIX. Rabbit eyes were treated by application of HCAF and MIX drops before UV-B exposure (79 J/m(2)). Corneal and scleral DNA oxidation damage, xanthine-oxidase (XO) activity and malondialdehyde levels (MDA) in corneal tissue and prostaglandin E(2) (PGE(2)) in the aqueous humour were reduced by HCAF alone and in combination with p-coumaric acid, showing their potential as a topical treatment against UV-B damage.
Fernandes, Merle; Sharma, Savitri
2013-04-01
To report a rare case of microsporidial and polymicrobial keratitis in a patient with Sjogren's syndrome and ocular cicatricial pemphigoid. This is a descriptive case report. A 66-year-old lady diagnosed with Sjogren's syndrome (SS) and ocular cicatricial pemphigoid (OCP) presented to us with microbial keratitis after using a Boston sclera contact lens for a painful epithelial defect. After 9 days of medical treatment, she underwent therapeutic penetrating keratoplasty. 10% potassium hydroxide and calcofluor white wet mount revealed microsporidial spores. Gram positive cocci and Gram variable bacilli on Gram stain were identified as Staphylococcus epidermidis and Corynebacterium accolens in culture. Histopathological examination of the corneal tissue confirmed the presence of microsporidial spores. Microsporidal keratitis can occur in patients with severe ocular surface disease due to SS and OCP. Predisposing factors include dry eye, local and systemic immunosuppression and Boston scleral contact lens. Early surgical intervention may be needed to eradicate the infection. Copyright © 2012 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
Horise, Yuki; He, Xingchi; Gehlbach, Peter; Taylor, Russell; Iordachita, Iulian
2015-01-01
In retinal surgery, microsurgical instruments such as micro forceps, scissors and picks are inserted through the eye wall via sclerotomies. A handheld intraocular light source is typically used to visualize the tools during the procedure. Retinal surgery requires precise and stable tool maneuvers as the surgical targets are micro scale, fragile and critical to function. Retinal surgeons typically control an active surgical tool with one hand and an illumination source with the other. In this paper, we present a "smart" light pipe that enables true bimanual surgery via utilization of an active, robot-assisted source of targeted illumination. The novel sensorized smart light pipe measures the contact force between the sclerotomy and its own shaft, thereby accommodating the motion of the patient's eye. Forces at the point of contact with the sclera are detected by fiber Bragg grating (FBG) sensors on the light pipe. Our calibration and validation results demonstrate reliable measurement of the contact force as well as location of the sclerotomy. Preliminary experiments have been conducted to functionally evaluate robotic intraocular illumination.
Importance of accurately assessing biomechanics of the cornea.
Roberts, Cynthia J
2016-07-01
This article summarizes the state-of-the-art in clinical corneal biomechanics, including procedures in which biomechanics play a role, and the clinical consequences in terms of error in estimating intraocular pressure (IOP). Corneal biomechanical response to refractive surgery can be categorized into either stable alteration of surface shape and thus visual outcome, or unstable biomechanical decompensation. The stable response is characterized by central flattening and peripheral steepening that is potentiated in a stiffer cornea. Two clinical devices for assessing corneal biomechanics do not yet measure classic biomechanical properties, but rather provide assessment of corneal deformation response. Biomechanical parameters are a function of IOP, and both the cornea and sclera become stiffer as IOP increases. Any assessment of biomechanical parameters must include IOP, and one value of stiffness does not adequately characterize a cornea. Corneal biomechanics plays a role in the outcomes of any procedure in which lamellae are transected. Once the corneal structure has been altered in a manner that includes central thinning, IOP measurements with applanation tonometry are likely not valid, and other technologies should be used.
Brillouin microscopy: assessing ocular tissue biomechanics.
Yun, Seok Hyun; Chernyak, Dimitri
2018-07-01
Assessment of corneal biomechanics has been an unmet clinical need in ophthalmology for many years. Many researchers and clinicians have identified corneal biomechanics as source of variability in refractive procedures and one of the main factors in keratoconus. However, it has been difficult to accurately characterize corneal biomechanics in patients. The recent development of Brillouin light scattering microscopy heightens the promise of bringing biomechanics into the clinic. The aim of this review is to overview the progress and discuss prospective applications of this new technology. Brillouin microscopy uses a low-power near-infrared laser beam to determine longitudinal modulus or mechanical compressibility of tissue by analyzing the return signal spectrum. Human clinical studies have demonstrated significant difference in the elastic properties of normal corneas versus corneas diagnosed with mild and severe keratoconus. Clinical data have also shown biomechanical changes after corneal cross-linking treatment of keratoconus patients. Brillouin measurements of the crystalline lens and sclera have also been demonstrated. Brillouin microscopy is a promising technology under commercial development at present. The technique enables physicians to characterize the biomechanical properties of ocular tissues.
Scleral and intraocular amoebic dissemination in Acanthamoeba keratitis.
Arnalich-Montiel, Francisco; Jaumandreu, Laia; Leal, Marina; Valladares, Basilio; Lorenzo-Morales, Jacob
2013-12-01
To review an Acanthamoeba keratitis case series for the documented extracorneal spread of the amoeba. A retrospective review of an observational case series from a single institution. Three patients with 4 instances of microbiologically confirmed extracorneal amoebic spread were identified. Patient 1 had nodular scleritis after undergoing penetrating keratoplasty and was treated successfully with double freeze-thaw cryotherapy; patient 2 had intraocular dissemination of the amoeba detected in a retrocorneal membrane; and patient 3 had, after undergoing tectonic keratoplasty, intraocular dissemination of the amoeba that was treated successfully with intraocular and systemic voriconazole and, afterwards, a nodular scleritis treated with double freeze-thaw cryotherapy and a large-diameter corneal graft to treat corneal recurrence. Acanthamoeba can migrate to the sclera or to the intraocular tissues in some instances, such as in long-standing disease or in penetrating keratoplasty. A prompt biopsy for microbiological analysis and early treatment are required, if this is suspected. Voriconazole can be effective for intraocular invasion when used orally and intraocularly. Scleral involvement might require a surgical approach with double freeze-thaw cryotherapy to treat the localized disease.
Demirci, Hakan; Steen, Daniel W
2014-01-01
To describe the limitations of Fourier-domain optical coherence tomography (OCT) in imaging common conjunctival and corneal pathology. Retrospective, single-center case series of 40 patients with conjunctival and cornea pathology. Fourier-domain OCT imaged laser in situ keratomileusis (LASIK) flaps in detail, including its relation to other corneal structures and abnormalities. Similarly, in infectious or degenerative corneal disorders, Fourier-domain OCT successfully showed the extent of infiltration or material deposition, which appeared as hyper-reflective areas. In cases with pterygium, the underlying cornea could not be imaged. All cases of common conjunctival pathologies, such as nevus or pinguecula, were successfully imaged in detail. Nevi, scleritis, pterygium, pinguecula, and subconjunctival hemorrhage were hyper-reflective lesions, while cysts and lymphangiectasia were hyporeflective. The details of the underlying sclera were not uniformly imaged in conjunctival pathologies. Fourier-domain OCT imaged the trabeculectomy bleb in detail, whereas the details of structures of the anterior chamber angle were not routinely visualized in all cases. Light scatter through vascularized, densely inflamed, or thick lesions limits the imaging capabilities of Fourier-domain anterior segment OCT.
Retinal pigment epithelium culture;a potential source of retinal stem cells.
Akrami, Hassan; Soheili, Zahra-Soheila; Khalooghi, Keynoush; Ahmadieh, Hamid; Rezaie-Kanavi, Mojgan; Samiei, Shahram; Davari, Malihe; Ghaderi, Shima; Sanie-Jahromi, Fatemeh
2009-07-01
To establish human retinal pigment epithelial (RPE) cell culture as a source for cell replacement therapy in ocular diseases. Human cadaver globes were used to isolate RPE cells. Each globe was cut into several pieces of a few millimeters in size. After removing the sclera and choroid, remaining tissues were washed in phosphate buffer saline and RPE cells were isolated using dispase enzyme solution and cultured in Dulbecco's Modified Eagle's Medium: Nutrient Mixture F-12 supplemented with 10% fetal calf serum. Primary cultures of RPE cells were established and spheroid colonies related to progenitor/stem cells developed in a number of cultures. The colonies included purely pigmented or mixed pigmented and non-pigmented cells. After multiple cellular passages, several types of photoreceptors and neural-like cells were detected morphologically. Cellular plasticity in RPE cell cultures revealed promising results in terms of generation of stem/progenitor cells from human RPE cells. Whether the spheroids and neural-like retinal cells were directly derived from retinal stem cells or offspring of trans-differentiating or de-differentiating RPE cells remains to be answered.
Retinal Pigment Epithelium Culture;a Potential Source of Retinal Stem Cells
Akrami, Hassan; Soheili, Zahra-Soheila; Khalooghi, Keynoush; Ahmadieh, Hamid; Rezaie-Kanavi, Mojgan; Samiei, Shahram; Davari, Malihe; Ghaderi, Shima; Sanie-Jahromi, Fatemeh
2009-01-01
Purpose To establish human retinal pigment epithelial (RPE) cell culture as a source for cell replacement therapy in ocular diseases. Methods Human cadaver globes were used to isolate RPE cells. Each globe was cut into several pieces of a few millimeters in size. After removing the sclera and choroid, remaining tissues were washed in phosphate buffer saline and RPE cells were isolated using dispase enzyme solution and cultured in Dulbecco’s Modified Eagle’s Medium: Nutrient Mixture F-12 supplemented with 10% fetal calf serum. Results Primary cultures of RPE cells were established and spheroid colonies related to progenitor/stem cells developed in a number of cultures. The colonies included purely pigmented or mixed pigmented and non-pigmented cells. After multiple cellular passages, several types of photoreceptors and neural-like cells were detected morphologically. Conclusion Cellular plasticity in RPE cell cultures revealed promising results in terms of generation of stem/progenitor cells from human RPE cells. Whether the spheroids and neural-like retinal cells were directly derived from retinal stem cells or offspring of trans-differentiating or de-differentiating RPE cells remains to be answered. PMID:23198062
Growth hormone receptor deficiency (Laron syndrome): clinical and genetic characteristics.
Guevara-Aguirre, J; Rosenbloom, A L; Vaccarello, M A; Fielder, P J; de la Vega, A; Diamond, F B; Rosenfeld, R G
1991-01-01
Approximately 60 cases of GHRD (Laron syndrome) were reported before 1990 and half of these were from Israel. We have described 47 additional patients from an inbred population of South Ecuador and have emphasized certain clinical features including: markedly advanced osseous maturation for height age; normal body proportions in childhood but child-like proportions in adults; much greater deviation of stature than head size, giving an appearance of large cranium and small facies; underweight in childhood despite the appearance of obesity and true obesity in adulthood; blue scleras; and limited elbow extension. The Ecuadorean patients differed markedly and most importantly from the other large concentration, in Israel, by being of normal or superior intelligence, suggesting a unique linkage in the Ecuadorean population. The Ecuadorean population also differed in that those patients coming from Loja province had a markedly skewed sex ratio (19 females: 2 males), while those from El Oro province had a normal sex distribution (14 females: 12 males). The phenotypic similarity between the El Oro and Loja patients indicates that this abnormal sex distribution is not a direct result of the GHRD.
Transmuscular Migration of a Scleral Tunnel-Secured Encircling Silicone Band.
Nishida, Yui; Fukumoto, Masanori; Kida, Teruyo; Suzuki, Hiroyuki; Ikeda, Tsunehiko
2016-01-01
The migration of an encircling silicone band through a rectus muscle is a rare postoperative complication associated with scleral buckling surgery for retinal detachment. In this present study, we describe what we believe to be the first reported case of a patient who experienced postoperative migration of an encircling silicone band through the rectus muscle, despite the band being surgically secured to the sclera in a scleral tunnel. A 58-year-old man presented with a rhegmatogenous retinal detachment in his left eye. Pars plana vitrectomy was performed with the placement of an encircling silicone band, and the patient's retina was successfully reattached. One year postoperatively, the encircling band became exposed on the nasal side of the conjunctiva next to the limbus without any symptoms. Two weeks later, the exposed encircling band was surgically removed without any complications. The findings of this study show that even when an encircling silicone band is surgically secured around the eye, periodic and careful postoperative follow-up examinations should be performed to ensure no migration of the band.
[Genetic mutation and clinical features of osteogenesis imperfecta type V].
Guan, Shizhen; Bai, Xue; Wang, Yi; Liu, Zhigang; Ren, Xiuzhi; Zhang, Tianke; Ju, Mingyan; Li, Keqiu; Li, Guang
2017-12-10
To explore genetic mutations and clinical features of osteogenesis imperfecta type V. Clinical record of five patients (including one familial case) with osteogenesis imperfecta type V were retrospectively analyzed. Peripheral blood samples of the patients, one family member, as well as healthy controls were collected. Mutation of IFITM5 gene was identified by PCR amplification and Sanger sequencing. A heterozygous mutation (c.-14C>T) in the 5-UTR of the IFITM5 gene was identified in all of the patients and one mother. The clinical findings included frequent fractures and spine and/or extremities deformities, absence of dentinogenesis imperfecta, absence of hearing impairment, and blue sclera in 1 case. Radiographic findings revealed calcification of the interosseous membrane between the radius-ulna in all cases. Hyperplastic callus formation was found in 3 cases. Four had radial-head dislocation. A single heterozygous mutation c.-14C>T was found in the 5-UTR of the IFITM5 gene in 5 patients with osteogensis imperfecta type V. The patients showed specific radiological features including calcification of interosseous membrane, hyperplastic callus formation, and radial-head dislocation.
Johnson, Leslie N; Cashman, Siobhan M; Kumar-Singh, Rajendra
2008-01-01
As in other organ systems, gene and drug delivery to ocular tissues such as the retina and cornea is hampered by inefficient penetration of therapeutic molecules across the plasma membrane. We describe the use of a novel peptide for ocular delivery (POD) with protein transduction properties, for delivery of small and large molecules across the plasma membrane. POD enters cells within 5 minutes in a temperature dependent manner. POD can compact and deliver plasmid DNA, achieving transgene expression in >50% of human embryonic retinoblasts. Delivery of small interfering RNA (siRNA) duplexes to cells using POD, allowed for silencing of transgene expression by >50%. POD could also be used to deliver quantum dots in vitro and in vivo. Upon ocular delivery, POD rapidly entered neural retina and localized to retinal pigment epithelium (RPE), photoreceptor, and ganglion cells. Additionally, POD was able to enter corneal epithelium, sclera, choroid, and the dura of the optic nerve via topical application. POD also functions as a bacteriostatic, a useful property for a carrier of molecules to post mitotic neural ocular tissues.
Fish skin as a model membrane: structure and characteristics.
Konrádsdóttir, Fífa; Loftsson, Thorsteinn; Sigfússon, Sigurdur Dadi
2009-01-01
Synthetic and cell-based membranes are frequently used during drug formulation development for the assessment of drug availability. However, most of the currently used membranes do not mimic mucosal membranes well, especially the aqueous mucous layer of the membranes. In this study we evaluated catfish (Anarichas lupus L) skin as a model membrane. Permeation of hydrocortisone, lidocaine hydrochloride, benzocaine, diethylstilbestrol, naproxen, picric acid and sodium nitrate through skin from a freshly caught catfish was determined in Franz diffusion cells. Both lipophilic and hydrophilic molecules permeate through catfish skin via hydrated channels or aqueous pores. No correlation was observed between the octanol/water partition coefficient of the permeating molecules and their permeability coefficient through the skin. Permeation through catfish skin was found to be diffusion controlled. The results suggest that permeation through the fish skin proceeds via a diffusion-controlled process, a process that is similar to drug permeation through the aqueous mucous layer of a mucosal membrane. In addition, the fish skin, with its collagen matrix structure, appears to possess similar properties to the eye sclera.
Aptel, Florent; Béglé, Aurélie; Razavi, Arash; Romano, Fabrice; Charrel, Thomas; Chapelon, Jean-Yves; Denis, Philippe; Lafon, Cyril
2014-09-01
Several physical methods can be used to coagulate the ciliary body and decrease intra-ocular pressure in patients with glaucoma. The study described here investigated the short- and long-term effects of high-intensity focused ultrasound (HIFU) cyclocoagulation on the aqueous humor production structures and outflow pathways. Thirty-four rabbit eyes were sonicated with a ring-shaped probe containing six miniaturized HIFU transducers. Light, scanning electron and transmission electron microscopy and corrosion casts were performed. In the affected regions, the epithelium of the ciliary processes was degenerated or necrotic and sloughed off. Examinations performed several months afterward revealed involution of the ciliary processes. Vascular corrosion cast revealed focal interruption of the ciliary body microvasculature. In most animals, a sustained fluid space was seen between the sclera, the ciliary body and the choroid, likely indicating an increase in the aqueous outflow by the uveoscleral pathway. These results suggest that HIFU cyclocoagulation has a dual effect on aqueous humor dynamics. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
McMullen, Richard J.; Clode, Alison B.; Pandiri, Arun Kumar R.; Malarkey, David E.; Michau, Tammy Miller; Gilger, Brian C.
2011-01-01
A case of epibulbar melanoma in a 6-month-old, gelded, chestnut Hanoverian foal is reported. The location and clinical appearance upon initial presentation led to the tentative diagnosis of staphyloma or a congenital mass of unknown origin. An attempt was made to surgically excise the mass under general anesthesia, but due to its infiltrative nature and intraoperative appearance, most, but not all was removed without compromising the integrity of the globe. Histopathological evaluation revealed a multinodular to packeted, poorly demarcated, unencapsulated, infiltrative exophytic melanocytic neoplasm composed of bundles and nests of plump spindloid to polygonal heavily pigmented epithelioid neoplastic cells interspersed with pigment-laden macrophages within a fine fibrovascular stroma. Upon examination after enucleation, neoplastic cells were found to infiltrate into the lateral cornea, sclera and the choroid. This is a unique case of an epibulbar melanoma with choroidal invasion in a foal. Based on the sudden onset and rapid growth as well as the histological evidence of invasion, well-differentiated features, heavy pigmentation, and no apparent mitoses, this neoplasm was considered to be a low-grade malignant melanoma. At 14 months after excision there is no evidence of recurrence. PMID:19046269
Transforming growth factor-beta in the chicken fundal layers: an immunohistochemical study.
Mathis, Ute; Schaeffel, Frank
2010-06-01
In the chicken model of myopia, it has first been shown that imposing defocus to the retina results in active remodelling of the sclera which, in turn, results in axial length changes of the eye. Transforming growth factor-beta (TGF-beta) is one of the scleral growth modulators but its cellular localization in the fundal layers, colocalization and function are not well known. The aim of the current study was to investigate the cellular distribution of the three isoforms TGF-beta1, 2 and 3 by immunohistochemical labelling. Furthermore, the effects of visual experience that induces refractive errors on TGF-beta2 labelling were examined. Transversal cryostat sections of the fundal layers were analyzed by indirect immunofluorescent labelling and cell counts. Visual experience was changed by having the chicks wear either diffusers, or positive or negative lenses of 7D power in front of the right eyes for various periods of time. Left eyes served as uncovered controls. All TGF-beta isoforms were localized in both scleral layers. In choroid, diffuse labelling of all isoforms was found. In retina, TGF-beta1 and 3 were detected in bipolar, amacrine and ganglion cells and TGF-beta2 in amacrine and ganglion cells. To further characterize these cells, double-labelling with known amacrine and bipolar cell markers was performed (calbindin, cellular retinoic acid binding protein (CRABP), Islet1, Lim3 and protein kinase C (PKC)). TGF-beta1, 2 and 3 could be colocalized with calbindin and CRABP in single amacrine cells. TGF-beta1-positive bipolar cells were immunoreactive to Lim3. TGF-beta1 and 3 were never colocalized with PKC in bipolar cells. Also, colocalization with peptides known to be involved in myopia development in chicks, such as glucagon, or vasointestinal polypeptide and the key enzyme for dopamine synthesis, tyrosine hydroxylase, was not observed. Lenses or diffusers, worn by the chicks for various periods of time, had no effect on TGF-beta2 immunoreactivity in choroid or sclera, or on the number of TGF-beta2 (active and latent form) expressing amacrine cells. This result did not change when the two identified populations of TGF-beta2 expressing amacrine cells (one calbindin-positive and the other CRABP-positive) were separately considered. Also no modulation was seen in choroid, although an earlier study had found changes in TGF-beta2 mRNA after lens treatment. The lack of any visually-induced changes in retina or choroid suggests that TGF-beta may not represent a key molecule in the retino-choroidal signalling cascade although it has previously been shown to have a primary role in scleral remodelling. Copyright 2010 Elsevier Ltd. All rights reserved.
Transporter targeted gatifloxacin prodrugs: Synthesis, permeability, and topical ocular delivery
Vooturi, Sunil K.; Kadam, Rajendra S.; Kompella, Uday B.
2013-01-01
Purpose To design and synthesize prodrugs of gatifloxacin targeting OCT, MCT, and ATB (0, +) transporters and to identify a prodrug with enhanced delivery to the back of the eye. Method Dimethylamino-propyl, carboxy-propyl, and amino-propyl(2-methyl) derivatives of gatifloxacin (GFX), DMAP-GFX, CP-GFX, and APM-GFX, were designed and synthesized to target OCT, MCT, and ATB (0, +) transporters, respectively. LC-MS method was developed to analyze drug and prodrug levels in various studies. Solubility and Log D (pH 7.4) were measured for prodrugs and the parent drug. Permeability of the prodrugs was determined in cornea, conjunctiva, and sclera-choroidretinal pigment epitheluim (SCRPE) and compared with gatifloxacin using Ussing chamber assembly. Permeability mechanisms were elucidated by determining the transport in the presence of transporter specific inhibitors. 1-Methyl-4-phenylpyridinium iodide (MPP+), nicotinic acid sodium salt, and α-methyl-DL-tryptophan were used to inhibit OCT, MCT, and ATB (0, +) transporters, respectively. A prodrug selected based on in vitro studies was administered as an eye drop to pigmented rabbits and the delivery to various eye tissues including vitreous humor was compared with gatifloxacin dosing. Results DMAP-GFX exhibited 12.8-fold greater solubility than GFX. All prodrugs were more lipophilic, with the measured Log D (pH 7.4) values ranging from 0.05 to 1.04, when compared to GFX (Log D: -1.15). DMAP-GFX showed 1.4-, 1.8-, and 1.9-fold improvement in permeability across cornea, conjunctiva, as well as SCRPE when compared to GFX. Moreover, it exhibited reduced permeability in the presence of MPP+ (competitive inhibitor of OCT), indicating OCT-mediated transport. CP-GFX showed 1.2-, 2.3- and 2.5-fold improvement in permeability across cornea, conjunctiva and SCRPE, respectively. In the presence of nicotinic acid (competitive inhibitor of MCT), permeability of CP-GFX was reduced across conjunctiva. However, cornea and SCRPE permeability of CP-GFX was not affected by nicotinic acid. APM-GFX did not show any improvement in permeability when compared to GFX across cornea, conjunctiva, and SCRPE. Based on solubility and permeability, DMAP-GFX was selected for in vivo studies. DMAP-GFX showed 3.6- and 1.95-fold higher levels in vitreous humor and CRPE compared to that of GFX at 1 hour after topical dosing. In vivo conversion of DMAP-GFX prodrug to GFX was quantified in tissues isolated at 1 hour after dosing. Prodrug-to-parent drug ratio was 8, 70, 24, 21, 29, 13, 55, and 60 % in cornea, conjunctiva, iris-ciliary body, aqueous humor, sclera, CRPE, retina, and vitreous humor, respectively. Conclusions DMAP-GFX prodrug enhanced solubility, Log D, as well as OCT mediated delivery of gatifloxacin to the back of the eye. PMID:23003105
Monte Carlo Simulation of Visible Light Diffuse Reflection in Neonatal Skin
NASA Astrophysics Data System (ADS)
Atencio, J. A. Delgado; Rodríguez, E. E.; Rodríguez, A. Cornejo; Rivas-Silva, J. F.
2008-04-01
Neonatal jaundice is a medical condition that happens commonly in newborns as result of desbalance between the production and the elimination of the bilirubin. Around 50% of newborns in term and something more of 60% of the near-term becomes jaundiced in the first week of life. This excess of bilirubin in the blood is exhibited in the skin, the sclera of the eyes and the mucous of mouth like a characteristic yellow coloration. In this work we make several numerical simulations of the spectral diffuse reflection for the skin of newborns that present different values of the biological parameters (bilirubin content, grade of pigmentation and content of blood) that characterize it. These simulations will allow us to evaluate the influence of these parameters on the experimental determination of bilirubin by noninvasive optical methods. The simulations are made in the spectral range of 400-700 nm using the Monte Carlo code MCML and two programs developed in LabVIEW by the authors. We simulated the diffuse reflection spectrum of neonatal skin for concentrations of bilirubin in skin that covers an ample range: from physiological to harmful numbers. We considered the influence of factors such as grade of pigmentation and content of blood.
Goiato, Marcelo Coelho; Fernandes, Aline Úrsula Rocha; dos Santos, Daniela Micheline; Hadadd, Marcela Filié; Moreno, Amália; Pesqueira, Aldiéris Alves
2011-02-01
The artificial iris is the structure responsible for the dissimulation and aesthetics of ocular prosthesis. The objective of the present study was to evaluate the color stability of artificial iris of microwaveable polymerized ocular prosthesis, as a function of paint type, drying method and accelerated aging. A total of 40 discs of microwaveable polymerized acrylic resin were fabricated, and divided according to the blue paint type (n = 5): hydrosoluble acrylic, nitrocellulose automotive, hydrosoluble gouache and oil paints. Paints where dried either at natural or at infrared light bulb method. Each specimen was constituted of one disc in colorless acrylic resin and another colored with a basic sclera pigment. Painting was performed in one surface of one of the discs. The specimens were submitted to an artificial aging chamber under ultraviolet light, during 1008 h. A reflective spectrophotometer was used to evaluate color changes. Data were evaluated by 3-way repeated-measures ANOVA and the Tukey HSD test (α = 0.05). All paints suffered color alteration. The oil paint presented the highest color resistance to artificial aging regardless of drying method. Copyright © 2010 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
The ocular skeleton through the eye of evo-devo.
Franz-Odendaal, Tamara Anne
2011-09-15
An evolutionary developmental (evo-devo) approach to understanding the evolution, homology, and development of structures has proved important for unraveling complex integrated skeletal systems through the use of modules, or modularity. An ocular skeleton, which consists of cartilage and sometimes bone, is present in many vertebrates; however, the origin of these two components remains elusive. Using both paleontological and developmental data, I propose that the vertebrate ocular skeleton is neural crest derived and that a single cranial neural crest module divided early in vertebrate evolution, possibly during the Ordovician, to give rise to an endoskeletal component and an exoskeletal component within the eye. These two components subsequently became uncoupled with respect to timing, placement within the sclera and inductive epithelia, enabling them to evolve independently and to diversify. In some extant groups, these two modules have become reassociated with one another. Furthermore, the data suggest that the endoskeletal component of the ocular skeleton was likely established and therefore evolved before the exoskeletal component. This study provides important insights into the evolution of the ocular skeleton, a region with a long evolutionary history among vertebrates. Copyright © 2011 Wiley-Liss, Inc., A Wiley Company.
New method for remote and repeatable monitoring of intraocular pressure variations.
Margalit, Israel; Beiderman, Yevgeny; Skaat, Alon; Rosenfeld, Elkanah; Belkin, Michael; Tornow, Ralf-Peter; Mico, Vicente; Garcia, Javier; Zalevsky, Zeev
2014-02-01
We present initial steps toward a new measurement device enabling high-precision, noncontact remote and repeatable monitoring of intraocular pressure (IOP)-based on an innovative measurement principle. Using only a camera and a laser source, the device measures IOP by tracking the secondary speckle pattern trajectories produced by the reflection of an illuminating laser beam from the iris or the sclera. The device was tested on rabbit eyes using two different methods to modify IOP: via an infusion bag and via mechanical pressure. In both cases, the eyes were stimulated with increasing and decreasing ramps of the IOP. As IOP variations changed the speckle distributions reflected back from the eye, data were recorded under various optical configurations to define and optimize the best experimental configuration for the IOP extraction. The association between the data provided by our proposed device and that resulting from controlled modification of the IOP was assessed, revealing high correlation (R2=0.98) and sensitivity and providing a high-precision measurement (5% estimated error) for the best experimental configuration. Future steps will be directed toward applying the proposed measurement principle in clinical trials for monitoring IOP with human subjects.
Yang, Bin; Jan, Ning-Jiun; Brazile, Bryn; Voorhees, Andrew; Lathrop, Kira L; Sigal, Ian A
2018-04-06
Collagen fibers play a central role in normal eye mechanics and pathology. In ocular tissues, collagen fibers exhibit a complex 3-dimensional (3D) fiber orientation, with both in-plane (IP) and out-of-plane (OP) orientations. Imaging techniques traditionally applied to the study of ocular tissues only quantify IP fiber orientation, providing little information on OP fiber orientation. Accurate description of the complex 3D fiber microstructures of the eye requires quantifying full 3D fiber orientation. Herein, we present 3dPLM, a technique based on polarized light microscopy developed to quantify both IP and OP collagen fiber orientations of ocular tissues. The performance of 3dPLM was examined by simulation and experimental verification and validation. The experiments demonstrated an excellent agreement between extracted and true 3D fiber orientation. Both IP and OP fiber orientations can be extracted from the sclera and the cornea, providing previously unavailable quantitative 3D measures and insight into the tissue microarchitecture. Together, the results demonstrate that 3dPLM is a powerful imaging technique for the analysis of ocular tissues. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
The effect of face eccentricity on the perception of gaze direction.
Todorović, Dejan
2009-01-01
The perception of a looker's gaze direction depends not only on iris eccentricity (the position of the looker's irises within the sclera) but also on the orientation of the lookers' head. One among several potential cues of head orientation is face eccentricity, the position of the inner features of the face (eyes, nose, mouth) within the head contour, as viewed by the observer. For natural faces this cue is confounded with many other head-orientation cues, but in schematic faces it can be studied in isolation. Salient novel illustrations of the effectiveness of face eccentricity are 'Necker faces', which involve equal iris eccentricities but multiple perceived gaze directions. In four experiments, iris and face eccentricity in schematic faces were manipulated, revealing strong and consistent effects of face eccentricity on perceived gaze direction, with different types of tasks. An additional experiment confirmed the 'Mona Lisa' effect with this type of stimuli. Face eccentricity most likely acted as a simple but robust cue of head turn. A simple computational account of combined effects of cues of eye and head turn on perceived gaze direction is presented, including a formal condition for the perception of direct gaze. An account of the 'Mona Lisa' effect is presented.
Something to sink your teeth into: The presence of teeth augments ERPs to mouth expressions.
daSilva, Elizabeth B; Crager, Kirsten; Geisler, Danika; Newbern, Powell; Orem, Benjamin; Puce, Aina
2016-02-15
If the whites of the sclera can impact neural processing of eye expressions (Hardee, Thompson, & Puce, 2008; Whalen et al., 1998), do seen teeth affect neural responses to mouth expressions? Twenty participants (10 females; ages 22-31) viewed avatar mouth images depicting grimaces, smiles and open mouth expressions that were presented with and without teeth. A continuous 256 channel electroencephalogram (EEG) was recorded while subjects completed two tasks: an implicit task evaluating stimulus color and an explicit task evaluating mouth expression valence. Event related potential (ERP) peak amplitudes and latencies and area under the curve (AUC) were measured in individual subject averaged ERPs. Statistical testing revealed a main effect of the presence of Teeth for P100, N170, and vertex positive potential (VPP) amplitudes and for slow positive wave (SPW) AUC. Task by teeth interactions occurred for P250 amplitude, underscoring how explicit task demands can influence neural processing. Arousal ratings co-varied with teeth presence, suggesting that low-level visual features such as teeth may drive the saliency of emotional expressions, and lie at the core of differences in neural processing to different emotional expressions. Copyright © 2015 Elsevier Inc. All rights reserved.
ReSure Sealant for Pars Plana Vitrectomy Wound Closure.
Ho, Vincent Y; Shah, Gaurav K; Liu, Enchun M
2015-01-01
ReSure Sealant (Ocular Therapeutix, Bedford, MA) is an ocular sealant that demonstrated both safety and effectiveness in a prospective, randomized clinical trial for sealing clear corneal incisions following cataract surgery and intraocular lens placement in adults.1 PATIENTS AND METHODS: This is the first literature report of ReSure Sealant used for the closure of 23-gauge (G) pars plana vitrectomy (PPV) sclerotomies. A 70-year-old pseudophakic female with a history of epiretinal membrane and branch retinal vein occlusion of the right eye underwent 23-G PPV, membrane peel, and air-fluid exchange and was found to have leaking subconjunctival air at the end of the case. A linear conjunctival incision was performed to access the sclerotomy site. The incisions were then carefully dried before the sealant was applied to seal both the sclera and conjunctiva. After polymerization, the sealant formed a polyethylene glycol (PEG) hydrogel that was 89% water and 9.44% PEG. PEG is a synthetic material that is non-toxic and inert and, thus, suitable for use in medical products. ReSure Sealant may be a safe, quick method to close sclerotomy wounds in select cases. [ Copyright 2015, SLACK Incorporated.
Adjustable sutures: experimental assessment of final muscle position.
Climenhaga, H W; Pearce, W G
1984-08-01
The likelihood of forward "creep" of muscles recessed with the use of adjustable loops of suture in the correction of strabismus was investigated. Twelve orthotropic dogs underwent both regular and loop recessions of the lateral and medial rectus muscles; the data for two of the dogs were excluded because of loss of muscles. Three months later it was found that in the majority of cases the recessed muscles had minimally advanced from the position of surgical placement. Although the type of recession made little difference to the results, the mean forward creep was much greater for the medial rectus muscles (1.55 +/- 0.68 mm [p less than 0.01] and 2.00 +/- 2.44 mm [p = 0.09] for those undergoing regular and loop recessions respectively) than for the lateral rectus muscles (0.35 +/- 0.58 mm and 0.60 +/- 0.62 mm respectively). During the operations the amount of contraction of the medial rectus muscle had been noted to vary. It is likely that in some instances the tension on the suture loops was insufficient to hold them taut, and the muscles therefore adhered to the sclera at variable sites. Hence, adequate intrinsic muscle tone may be important for predictable clinical results of loop recession.
Dose-Effect Relationships for Recurrence of Keloid and Pterygium After Surgery and Radiotherapy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kal, Henk B.; Veen, Ronald E.; Juergenliemk-Schulz, Ina M.
2009-05-01
Purpose: To show radiation dose-response relationships for recurrence of keloid and pterygium after radiotherapy following surgery. Methods and Materials: Using PubMed, we performed a retrospective review of articles reporting incidences and/or dose-response relationships for recurrence of keloid and pterygium after radiotherapy following surgery. The irradiation regimens identified were normalized by use of the linear-quadratic model; biologically effective doses (BEDs) were calculated. Results: For keloid recurrence after radiotherapy following keloid removal, with either teletherapy or brachytherapy, the recurrence rate after having delivered a BED greater than 30 Gy is less than 10%. For pterygium recurrence after bare sclera surgery and {supmore » 90}Sr {beta}-irradiation, a BED of about 30 Gy seems to be sufficient also to reduce the recurrence rate to less than 10%. Conclusions: Most of the doses in the radiotherapy schemes used for prevention of keloid recurrence after surgery are too low. In contrast, the doses applied in most regimens to prevent pterygium recurrence are too high. A scheme with a BED of 30 to 40 Gy seems to be sufficient to prevent recurrences of keloid as well as pterygium.« less
Radial optic neurotomy for ischaemic central vein occlusion
Martínez-Jardón, C S; Meza-de Regil, A; Dalma-Weiszhausz, J; Leizaola-Fernández, C; Morales-Cantón, V; Guerrero-Naranjo, J L; Quiroz-Mercado, H
2005-01-01
Background/aims: Ischaemic central retinal vein occlusion (CRVO) accounts for 20–50% of all CRVO. No treatment has been proved to be effective. The efficacy of radial optic neurotomy (RON) was evaluated in eyes with ischaemic CRVO. Methods: 10 patients with ischaemic CRVO underwent RON. After pars plana vitrectomy, a microvitreoretinal blade was used to incise the scleral ring, cribriform plate, and adjacent sclera at the nasal edge of the optic disc. Best corrected visual acuity (BCVA), intraocular pressure (IOP), fluorescein angiography (FA), multifocal electroretinography (mfERG), and optical coherence tomography (OCT) were measured preoperatively and at 1, 3, and 6 months postoperatively. Results: No visual improvement was noted in the eyes that underwent RON. FA and mfERG showed no increase in retinal perfusion or retinal function postoperatively. Mean macular central thickness changed from 841 (SD 170) μm preoperatively to 162 (SD 34) μm at the sixth postoperative month. One patient had retinal central artery perforation intraoperatively. One patient developed neovascular glaucoma. Conclusion: RON in ischaemic CRVO did not improve visual function (by mfERG) or visual acuity although macular thickness did improve. This technique may be associated with potential risks. Randomised studies are needed to corroborate these results. PMID:15834084
Chimpanzees and Humans Mimic Pupil-Size of Conspecifics
Kret, Mariska E.; Tomonaga, Masaki; Matsuzawa, Tetsuro
2014-01-01
Group-living typically provides benefits to individual group members but also confers costs. To avoid incredulity and betrayal and allow trust and cooperation, individuals must understand the intentions and emotions of their group members. Humans attend to other's eyes and from gaze and pupil-size cues, infer information about the state of mind of the observed. In humans, pupil-size tends to mimic that of the observed. Here we tested whether pupil-mimicry exists in our closest relative, the chimpanzee (P. troglodytes). We conjectured that if pupil-mimicry has adaptive value, e.g. to promote swift communication of inner states and facilitate shared understanding and coordination, pupil-mimicry should emerge within but not across species. Pupillometry data was collected from human and chimpanzee subjects while they observed images of the eyes of both species with dilating/constricting pupils. Both species showed enhanced pupil-mimicry with members of their own species, with effects being strongest in humans and chimpanzee mothers. Pupil-mimicry may be deeply-rooted, but probably gained importance from the point in human evolution where the morphology of our eyes became more prominent. Humans' white sclera surrounding the iris, and the fine muscles around their eyes facilitate non-verbal communication via eye signals. PMID:25140998
Micro-mechanical model for the tension-stabilized enzymatic degradation of collagen tissues
NASA Astrophysics Data System (ADS)
Nguyen, Thao; Ruberti, Jeffery
We present a study of how the collagen fiber structure influences the enzymatic degradation of collagen tissues. Experiments of collagen fibrils and tissues show that mechanical tension can slow and halt enzymatic degradation. Tissue-level experiments also show that degradation rate is minimum at a stretch level coincident with the onset of strain-stiffening in the stress response. To understand these phenomena, we developed a micro-mechanical model of a fibrous collagen tissue undergoing enzymatic degradation. Collagen fibers are described as sinusoidal elastica beams, and the tissue is described as a distribution of fibers. We assumed that the degradation reaction is inhibited by the axial strain energy of the crimped collagen fibers. The degradation rate law was calibrated to experiments on isolated single fibrils from bovine sclera. The fiber crimp and properties were fit to uniaxial tension tests of tissue strips. The fibril-level kinetic and tissue-level structural parameters were used to predict tissue-level degradation-induced creep rate under a constant applied force. We showed that we could accurately predict the degradation-induce creep rate of the pericardium and cornea once we accounted for differences in the fiber crimp structure and properties.
Direct trabecular meshwork imaging in porcine eyes through multiphoton gonioscopy
Masihzadeh, Omid; Ammar, David A.; Kahook, Malik Y.; Gibson, Emily A.; Lei, Tim C.
2013-01-01
Abstract. The development of technologies to characterize the ocular aqueous outflow system (AOS) is important for the understanding of the pathophysiology of glaucoma. Multiphoton microscopy (MPM) offers the advantage of high-resolution, label-free imaging with intrinsic image contrast because the emitted signals result from the specific biomolecular content of the tissue. Previous attempts to use MPM to image the murine irido-corneal region directly through the sclera have suffered from degradation in image resolution due to scattering of the focused laser light. As a result, transscleral MPM has limited ability to observe fine structures in the AOS. In this work, the porcine irido-corneal angle was successfully imaged through the transparent cornea using a gonioscopic lens to circumvent the highly scattering scleral tissue. The resulting high-resolution images allowed the detailed structures in the trabecular meshwork (TM) to be observed. Multimodal imaging by two-photon autofluorescence and second harmonic generation allowed visualization of different features in the TM without labels and without disruption of the TM or surrounding tissues. MPM gonioscopy is a promising noninvasive imaging tool for high-resolution studies of the AOS, and research continues to explore the potential for future clinical applications in humans. PMID:23515864
Direct trabecular meshwork imaging in porcine eyes through multiphoton gonioscopy.
Masihzadeh, Omid; Ammar, David A; Kahook, Malik Y; Gibson, Emily A; Lei, Tim C
2013-03-01
The development of technologies to characterize the ocular aqueous outflow system (AOS) is important for the understanding of the pathophysiology of glaucoma. Multiphoton microscopy (MPM) offers the advantage of high-resolution, label-free imaging with intrinsic image contrast because the emitted signals result from the specific biomolecular content of the tissue. Previous attempts to use MPM to image the murine irido-corneal region directly through the sclera have suffered from degradation in image resolution due to scattering of the focused laser light. As a result, transscleral MPM has limited ability to observe fine structures in the AOS. In this work, the porcine irido-corneal angle was successfully imaged through the transparent cornea using a gonioscopic lens to circumvent the highly scattering scleral tissue. The resulting high-resolution images allowed the detailed structures in the trabecular meshwork (TM) to be observed. Multimodal imaging by two-photon autofluorescence and second harmonic generation allowed visualization of different features in the TM without labels and without disruption of the TM or surrounding tissues. MPM gonioscopy is a promising noninvasive imaging tool for high-resolution studies of the AOS, and research continues to explore the potential for future clinical applications in humans.
Direct trabecular meshwork imaging in porcine eyes through multiphoton gonioscopy
NASA Astrophysics Data System (ADS)
Masihzadeh, Omid; Ammar, David A.; Kahook, Malik Y.; Gibson, Emily A.; Lei, Tim C.
2013-03-01
The development of technologies to characterize the ocular aqueous outflow system (AOS) is important for the understanding of the pathophysiology of glaucoma. Multiphoton microscopy (MPM) offers the advantage of high-resolution, label-free imaging with intrinsic image contrast because the emitted signals result from the specific biomolecular content of the tissue. Previous attempts to use MPM to image the murine irido-corneal region directly through the sclera have suffered from degradation in image resolution due to scattering of the focused laser light. As a result, transscleral MPM has limited ability to observe fine structures in the AOS. In this work, the porcine irido-corneal angle was successfully imaged through the transparent cornea using a gonioscopic lens to circumvent the highly scattering scleral tissue. The resulting high-resolution images allowed the detailed structures in the trabecular meshwork (TM) to be observed. Multimodal imaging by two-photon autofluorescence and second harmonic generation allowed visualization of different features in the TM without labels and without disruption of the TM or surrounding tissues. MPM gonioscopy is a promising noninvasive imaging tool for high-resolution studies of the AOS, and research continues to explore the potential for future clinical applications in humans.
Congenital keratoglobus with multiple cardiac anomalies: a case presentation and literature review.
Ozer, Pinar A; Yalniz-Akkaya, Zuleyha
2015-07-01
Keratoglobus is a rare condition of bilateral corneal ectasia, which results in high myopia, irregular astigmatism, scarring, and rarely spontaneous globe rupture. Globoid protrusion of a clear, diffusely thin cornea is the pathology. The congenital form has been associated with blue sclera in which there is a systemic connective tissue disorder with abnormal collagen synthesis like Ehlers-Danlos syndrome, Marfan syndrome, and osteogenesis imperfecta. Some concomitant abnormalities reported with kertoglobus include joint hypermobility, dental and skeletal abnormalities, osteal fragility, and deafness. Acquired forms have been reported to be associated with vernal keratoconjunctivitis and thyroid ophthalmopathy. We report the case of a 16-year-old boy with keratoglobus who presented with a history of photophobia and a low vision in both eyes since birth. He has been followed up by our pediatric cardiology department due to multiple cardiac anomalies. He had hypermobility of large joints, easy bruising, thin and hyperextensible skin with visible veins, which were also described in his elder brother. We aimed to discuss the etiology and the association of keratoglobus with some systemic abnormalities caused by collogen tissue disturbance, and make a brief review about the recent literature concerning the management of keratoglobus patients.
Kivelä, Tero T
2018-03-01
James Wardrop (1782-1869), a young Scottish surgeon and an early ophthalmologist in Edinburgh, is credited for describing in 1809 retinoblastoma as an entity in his treatise 'Observations on Fungus Haematodes or Soft Cancer'. His treatise also reveals that Allan Burns (1781-1813), another young Scottish surgeon and anatomist, had invited Wardrop to assist in enucleating an eye from a 41-year-old Glasgow woman who, in retrospect, had a uveal melanoma. Her eye had become blind 4 months after symptoms of exudative retinal detachment had appeared, and it had become painful after a further 2-4 months. The tumour eventually perforated the sclera, and she died within a year thereafter of hepatic metastases. Burns and Wardrop went on to publish detailed parallel accounts of the symptoms, signs, ophthalmic pathology and post-mortem findings regarding the primary, recurrent and metastatic tumour. Burns may have performed the post-mortem after exhuming the body, a common occurrence in early 19th Century Scotland, a thriving hub for teaching morbid anatomy to young surgeons at the time. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
Corneal Vibrations during Intraocular Pressure Measurement with an Air-Puff Method
Wilczyński, Sławomir
2018-01-01
Introduction The paper presents a commentary on the method of analysis of corneal vibrations occurring during eye pressure measurements with air-puff tonometers, for example, Corvis. The presented definition and measurement method allow for the analysis of image sequences of eye responses—cornea deformation. In particular, the outer corneal contour and sclera fragments are analysed, and 3D reconstruction is performed. Methods On this basis, well-known parameters such as eyeball reaction or corneal response are determined. The next steps of analysis allow for automatic and reproducible separation of four different corneal vibrations. These vibrations are associated with (1) the location of the maximum of cornea deformation; (2) the cutoff area measured in relation to the cornea in a steady state; (3) the maximum of peaks occurring between applanations; and (4) the other characteristic points of the corneal contour. Results The results obtained enable (1) automatic determination of the amplitude of vibrations; (2) determination of the frequency of vibrations; and (3) determination of the correlation between the selected types of vibrations. Conclusions These are diagnostic features that can be directly applied clinically for new and archived data. PMID:29610655
Patruno, M; Perazzi, A; Martinello, T; Blaseotto, A; Di Iorio, E; Iacopetti, I
2017-06-01
The cornea provides protection and transparency to the eye, allowing an optimal sharpness view. In some pathological conditions the cornea is able to regenerate thanks to the presence of a stem cells reservoir present at the level of the transition area between cornea and sclera (limbus). Corneal cell therapies in Veterinary Medicine are really limited due to the lacking of knowledge about the anatomy of the limbal area, the putative presence of stem cells and their identification in domestic species. The aim of this study was to provide an overview of the main distinctive structural features of the sclero-corneal junction and conjunctival-corneal junction areas in some species of veterinary importance, using optic microscope observations of histological sections. The resulting data were compared with cornea from humans adapting protocols already used to identify stem cells by means of a specific cellular marker. We tested the expression of ΔNp63α isoform in the cornea basal cells, trying to correlate the distribution profile with areas of highly proliferative turnover. The results obtained from this study represent a first step towards the identification of a corneal stem cells reservoir in different animals.
Scleritis Caused by In Vitro Linezolid-Resistant Nocardia asteroides
Tuli, Sonal
2014-01-01
Purpose. To describe a case of postoperative scleritis caused by a novel strain of Nocardia resistant to linezolid and trimethoprim-sulfamethoxazole (TMP-SMX). Methods. Case report of a patient with microbiologically proven scleritis due to Nocardia asteroides. Results. The patient presented with pain, redness, and nodules on the sclera three months following pterygium excision with mitomycin C and amniotic membrane placement. As no response was noted with empiric treatment for bacterial scleritis, debridement was performed. The cytopathology report showed gram positive filamentous bacteria. A presumptive diagnosis of Nocardia scleritis was made and therapy was initiated based on a literature review on treatments for Nocardia infections. Cultures returned growing Nocardia asteroides. Antibiotic sensitivity testing revealed resistance to linezolid and TMP-SMX which are the traditional drugs of choice for Nocardia. The patient was treated with amikacin and imipenem as well as extensive debridement with pedicle grafts. The patient's scleritis resolved with a good visual outcome. Conclusions. Cultures should be obtained in all cases of necrotizing scleritis in patients with a recent history of conjunctival surgery to rule out unusual organisms such as Nocardia. Although literature states that resistance to linezolid and TMP-SMX is rare in Nocardia, sensitivity testing can be useful in unresponsive cases. PMID:25400961
Scleritis Caused by In Vitro Linezolid-Resistant Nocardia asteroides.
Gonzalez, Andres; Fakhar, Kaihan; Gubernick, David; Tuli, Sonal
2014-01-01
Purpose. To describe a case of postoperative scleritis caused by a novel strain of Nocardia resistant to linezolid and trimethoprim-sulfamethoxazole (TMP-SMX). Methods. Case report of a patient with microbiologically proven scleritis due to Nocardia asteroides. Results. The patient presented with pain, redness, and nodules on the sclera three months following pterygium excision with mitomycin C and amniotic membrane placement. As no response was noted with empiric treatment for bacterial scleritis, debridement was performed. The cytopathology report showed gram positive filamentous bacteria. A presumptive diagnosis of Nocardia scleritis was made and therapy was initiated based on a literature review on treatments for Nocardia infections. Cultures returned growing Nocardia asteroides. Antibiotic sensitivity testing revealed resistance to linezolid and TMP-SMX which are the traditional drugs of choice for Nocardia. The patient was treated with amikacin and imipenem as well as extensive debridement with pedicle grafts. The patient's scleritis resolved with a good visual outcome. Conclusions. Cultures should be obtained in all cases of necrotizing scleritis in patients with a recent history of conjunctival surgery to rule out unusual organisms such as Nocardia. Although literature states that resistance to linezolid and TMP-SMX is rare in Nocardia, sensitivity testing can be useful in unresponsive cases.
Clinical and Molecular Characterization of Osteogenesis Imperfecta Type V
Brizola, Evelise; Mattos, Eduardo P.; Ferrari, Jessica; Freire, Patricia O.A.; Germer, Raquel; Llerena Jr, Juan C.; Félix, Têmis M.
2015-01-01
Osteogenesis imperfecta type V (OI-V) has a wide clinical variability, with distinct clinical/radiological features, such as calcification of the interosseous membrane (CIM) between the radius-ulna and/or tibia-fibula, hyperplastic callus (HPC) formation, dislocation of the radial head (DRH), and absence of dentinogenesis imperfecta (DI). Recently, a single heterozygous mutation (c.-14C>T) in the 5′UTR of the IFITM5 gene was identified to be causative for OI-V. Here, we describe 7 individuals from 5 unrelated families that carry the c.-14C>T IFITM5 mutation. The clinical findings in these cases are: absence of DI in all patients, presence of blue sclera in 2 cases, and 4 patients with DRH. Radiographic findings revealed HPC in 3 cases. All patients presented CIM between the radius and ulna, while 4 patients presented additional CIM between the tibia and fibula. Spinal fractures by vertebral compression were observed in all individuals. The proportion of cases identified with this mutation represents 4% of OI cases at our institution. The clinical identification of OI-V is crucial, as this mutation has an autosomal dominant inheritance with variable expressivity. PMID:26648832
Shoshi, Mire; Shoshi, Avdyl; Xhafa, Agim; Kastrati, Fetije; Shoshi, Fitore; Shoshi, Fjolla
2012-01-01
In the Eye Clinic during 2008-2010 we have treated 446 patients, where 252 were hospitalized patients while 184 weren't. Treated patients were 1-85 years old. AIM OF THIS STUDY is to present our experience in treatment of patients with eye lids injuries and their reconstruction. In patients that were treated in the Eye Clinic, we have applied surgical methods, anti-tetanic protection and local and general medical therapy. 252 hospitalized patients also had other injuries of eye such as: rupture of bulbus, traumatic cataract, prolapsus iris, hyphaema in CA, prolapsus CV, VLC perforanc cornea et corpus alieni in CA, hyphaema totalis, VLC sclera, corpus alieni intrabulbares. Patients that weren't hospitalized were 5-10 years old, 25-35 years old and 20-25 years old. Hospitalized patients were 5-10 years old, 20-25 years old and 30-35 years old. By this we can conclude that there wasn't any significant difference based on the patients' age. In the hospitalized cases with eye-lid injuries, most injuries of the eye were: VLC perforanc cornea cum prolapsus iridea, Corpus alieni in CA et hyphaema.
Driver's side curtain air bag-related globe rupture.
Porter, Ashley J; Hayes, Rylan; Lee, Lawrence; O'Hagan, Stephen
2018-06-04
A 35-year-old man presented after a high-speed motor vehicle accident and the driver's side curtain air bag causing blunt force trauma rupturing his right globe. The tangential force of the air bag resulted in an unusual arcuate horseshoe-shaped rupture through the lateral rectus insertion, causing avulsion of the muscle and tearing the sclera, with the apices of the tear extending anteriorly towards the limbus. Repair of the globe rupture was undertaken, and secondary vitrectomy revealed that the scleral tear had not involved the retina abutting the ora serrata. Silicone oil tamponade was used to fill the globe and the postoperative best corrected vision was 6/9. This is the first reported case of a ruptured globe caused by a side curtain air bag, resulting in a uniquely shaped arcuate scleral wound combined with lateral rectus avulsion, not associated with rhegmatogenous retinal damage, and is the first air bag-related globe rupture with scleral involvement to report a final best-corrected visual acuity better than 6/60. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Material Properties of Human Ocular Tissue at 7-µm Resolution.
Rohrbach, Daniel; Ito, Kazuyo; Lloyd, Harriet O; Silverman, Ronald H; Yoshida, Kenji; Yamaguchi, Tadashi; Mamou, Jonathan
2017-09-01
Quantitative assessment of the material properties of ocular tissues can provide valuable information for investigating several ophthalmic diseases. Quantitative acoustic microscopy (QAM) offers a means of obtaining such information, but few QAM investigations have been conducted on human ocular tissue. We imaged the optic nerve (ON) and iridocorneal angle in 12-µm deparaffinized sections of the human eye using a custom-built acoustic microscope with a 250-MHz transducer (7-µm lateral resolution). The two-dimensional QAM maps of ultrasound attenuation (α), speed of sound ( c), acoustic impedance ( Z), bulk modulus ( K), and mass density (ρ) were generated. Scanned samples were then stained and imaged by light microscopy for comparison with QAM maps. The spatial resolution and contrast of scanning acoustic microscopy (SAM) maps were sufficient to resolve anatomic layers of the retina (Re); anatomic features in SAM maps corresponded to those seen by light microscopy. Significant variations of the acoustic parameters were found. For example, the sclera was 220 MPa stiffer than Re, choroid, and ON tissue. To the authors' knowledge, this is the first systematic study to assess c, Z, K, ρ, and α of human ocular tissue at the high ultrasound frequencies used in this study.
Miyake-Apple view of inner side of sclerotomy during microincision vitrectomy surgery.
Inoue, Makoto; Ota, Ichiro; Taniuchi, Shutaro; Nagamoto, Toshiyuki; Miyake, Kensaku; Hirakata, Akito
2011-08-01
To examine the inner surface of the sclerotomy during microincision vitrectomy surgery by Miyake-Apple view. The anterior half of porcine eyes was attached to a transparent acrylic plate with cyanoacrylate glue. Then, either a 23-gauge or a 25-gauge trocar-cannula was inserted through the sclera obliquely. The inner surface of the entrance site was observed posteriorly by Miyake-Apple view. These images were compared with the endoscopic view of two patients who underwent vitreous surgery for an epiretinal membrane. When the trocar-cannula was inserted obliquely, the Miyake-Apple view showed that the ciliary epithelium at the sclerotomy site was stretched. When the trocar-cannula was inserted vertically, the ciliary epithelium was folded, and the folds remained even after the trocar was removed. Vitreous strands were seen incarcerated into the sclerotomy site. In human eyes, a folding of the ciliary epithelium was not clearly seen with the endoscopic view but the incarcerated vitreous was seen. The Miyake-Apple view provided a precise, in vivo, observation of the inner surface of the entry site. It disclosed the morphological stress on the ciliary epithelium by the sclerotomy. © 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.
Pino, M; Stingelin, N; Tanner, K E
2008-11-01
The skirt of an artificial cornea must integrate the implant to the host sclera, a major failure of present devices. Thus, it is highly desirable to encourage the metabolic activity of the cornea by using more bioactive, flexible skirt materials. Here we describe attempts to increase the bioactivity of polyether ether ketone (PEEK), high-density polyethylene (HDPE) and ultra-high molecular weight polyethylene (UHMWPE) films. The effectiveness of different strength NaOH pre-treatments to initiate apatite deposition on PEEK, HDPE and UHMWPE is investigated. We find that exposure of PEEK, HDPE and UHMWPE films to NaOH solutions induces the formation of potential nuclei for apatite (calcium phosphate), from which the growth of an apatite coating is stimulated when subsequently immersing the polymer films in 1.5 strength Simulated Body Fluid (SBF). As immersion time in SBF increases, further nucleation and growth produces a thicker and more compact apatite coating that can be expected to be highly bioactive. Interestingly, the apatite growth is found to also be dependent on both the concentration of NaOH solution and the structure of the polymer surface.
Spontaneous Findings in the Eyes of Cynomolgus Monkeys ( Macaca fascicularis) of Mauritian Origin.
Woicke, Jochen; Haile, Solomon; Mysore, Jagannatha; Peden, W Michael; Lejeune, Typhaine; Sanderson, Thomas; Brodie, Thomas
2018-04-01
Spontaneous findings noted in the eyes of Mauritian cynomolgus monkeys are described and descriptions are supplemented with illustrations. Findings observed after extensive histopathologic examinations (20 to 44 sections per eye) from 20 control, 17 treatment-naive stock monkeys, and 2 findings noted in drug-treated monkeys that were considered to be spontaneous are included. Also included are findings from 361 control monkeys of routine toxicity studies performed at our laboratories, for most of which a standard histopathological examination of 1 section per eye was conducted. Common observations in monkeys examined extensively and in historical controls were limited to lymphocytic or mononuclear cell infiltrations of the uvea and/or conjunctiva/sclera and, less commonly observed, melanocytoma of the ciliary body or iris. Findings noted only in monkeys examined extensively consisted of inflammation of the conjunctiva, ora serrata cysts, glial nodules, focal degeneration of the retina, cystoid degeneration of the central retina, ballooning degeneration of the ciliary epithelium, cyst of the ciliary body, and decreased pigmentation of the retinal pigment epithelium. Changes recorded only in historical controls included retinal atrophy and nuclear displacement in the retina. Lesions are discussed and compared with pertinent literature.
Management of long-standing partially torn and flipped laser in situ keratomileusis flaps.
Kim, Jin Sun; Chung, Byunghoon; Lee, Taekjune; Kim, Woon Cho; Kim, Tae-im; Kim, Eung Kweon
2015-02-01
We describe 2 cases of traumatized and torn laser in situ keratomileusis (LASIK) flaps, partially flipped anteriorly or posteriorly, fixed for 8 months or 4 months, and accompanied by epithelial ingrowth. The 2 patients had had uneventful bilateral LASIK 6 years and 1 year before the trauma. In Case 1, the anteriorly flipped flap was removed with transepithelial phototherapeutic keratectomy. Next, mitomycin-C 0.04% was applied for 30 seconds. In Case 2, the portion of the flap that was flipped posteriorly and buried under the remaining intact LASIK flap was restored to its original normal position and epithelial ingrowth was removed mechanically with a microcurette. Irrigation with 20% ethanol was performed to inhibit the recurrence of interfacial epithelial ingrowth. The stretched amniotic membrane overlay over the cornea and sclera was sutured tightly to the episclera as the biologic pressure patch for the inhibition of epithelial re-ingrowth. Good visual acuity was restored in both cases. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.
Transporter targeted gatifloxacin prodrugs: synthesis, permeability, and topical ocular delivery.
Vooturi, Sunil K; Kadam, Rajendra S; Kompella, Uday B
2012-11-05
In this work, we aim to design and synthesize prodrugs of gatifloxacin targeting organic cation transporter (OCT), monocarboxylate transporter (MCT), and ATB (0, +) transporters and to identify a prodrug with enhanced delivery to the back of the eye. Dimethylamino-propyl, carboxy-propyl, and amino-propyl(2-methyl) derivatives of gatifloxacin (GFX), DMAP-GFX, CP-GFX, and APM-GFX, were designed and synthesized to target OCT, MCT, and ATB (0, +) transporters, respectively. An LC-MS method was developed to analyze drug and prodrug levels in various studies. Solubility and log D (pH 7.4) were measured for prodrugs and the parent drug. The permeability of the prodrugs was determined in the cornea, conjunctiva, and sclera-choroid-retinal pigment epitheluim (SCRPE) and compared with gatifloxacin using an Ussing chamber assembly. Permeability mechanisms were elucidated by determining the transport in the presence of transporter specific inhibitors. 1-Methyl-4-phenylpyridinium iodide (MPP+), nicotinic acid sodium salt, and α-methyl-DL-tryptophan were used to inhibit OCT, MCT, and ATB (0, +) transporters, respectively. A prodrug selected based on in vitro studies was administered as an eye drop to pigmented rabbits, and the delivery to various eye tissues including vitreous humor was compared with gatifloxacin dosing. DMAP-GFX exhibited 12.8-fold greater solubility than GFX. All prodrugs were more lipophilic, with the measured log D (pH 7.4) values ranging from 0.05 to 1.04, when compared to GFX (log D: -1.15). DMAP-GFX showed 1.4-, 1.8-, and 1.9-fold improvement in permeability across the cornea, conjunctiva, and SCRPE when compared to GFX. Moreover, it exhibited reduced permeability in the presence of MPP+ (competitive inhibitor of OCT), indicating OCT-mediated transport. CP-GFX showed 1.2-, 2.3-, and 2.5-fold improvement in permeability across the cornea, conjunctiva, and SCRPE, respectively. In the presence of nicotinic acid (competitive inhibitor of MCT), the permeability of CP-GFX was reduced across the conjunctiva. However, the cornea and SCRPE permeability of CP-GFX was not affected by nicotinic acid. APM-GFX did not show any improvement in permeability when compared to GFX across the cornea, conjunctiva, and SCRPE. Based on solubility and permeability, DMAP-GFX was selected for in vivo studies. DMAP-GFX showed 3.6- and 1.95-fold higher levels in vitreous humor and CRPE compared to that of GFX at 1 h after topical dosing. In vivo conversion of DMAP-GFX prodrug to GFX was quantified in tissues isolated at 1 h after dosing. The parent drug-to-prodrug ratio was 8, 70, 24, 21, 29, 13, 55, and 60% in the cornea, conjunctiva, iris-ciliary body, aqueous humor, sclera, CRPE, retina, and vitreous humor, respectively. In conclusion, DMAP-GFX prodrug enhanced solubility, log D, as well as OCT mediated delivery of gatifloxacin to the back of the eye.
The fluid mechanics of scleral buckling surgery for the repair of retinal detachment.
Foster, William Joseph; Dowla, Nadia; Joshi, Saurabh Y; Nikolaou, Michael
2010-01-01
Scleral buckling is a common surgical technique used to treat retinal detachments that involves suturing a radial or circumferential silicone element on the sclera. Although this procedure has been performed since the 1960s, and there is a reasonable experimental model of retinal detachment, there is still debate as to how this surgery facilitates the re-attachment of the retina. Finite element calculations using the COMSOL Multiphysics system are utilized to explain the influence of the scleral buckle on the flow of sub-retinal fluid in a physical model of retinal detachment. We found that, by coupling fluid mechanics with structural mechanics, laminar fluid flow and the Bernoulli effect are necessary for a physically consistent explanation of retinal reattachment. Improved fluid outflow and retinal reattachment are found with low fluid viscosity and rapid eye movements. A simulation of saccadic eye movements was more effective in removing sub-retinal fluid than slower, reading speed, eye movements in removing subretinal fluid. The results of our simulations allow us to explain the physical principles behind scleral buckling surgery and provide insight that can be utilized clinically. In particular, we find that rapid eye movements facilitate more rapid retinal reattachment. This is contradictory to the conventional wisdom of attempting to minimize eye movements.
A novel technology using transscleral ultrasound to deliver protein loaded nanoparticles.
Huang, Di; Wang, Lili; Dong, Yixuan; Pan, Xin; Li, Ge; Wu, Chuanbin
2014-09-01
This study was designed to investigate the feasibility of silk fibroin nanoparticles (SFNs) for sustained drug delivery in transscleral ultrasound. Fluorescein isothiocynate labeled bovine serum albumin (FITC-BSA, MW 66.45 kDa) was chosen as a model macromolecular protein drug and SFNs were used as nano-carrier systems suitable for ocular drug delivery. Drug loaded nanoparticles (FITC-BSA-SFNs) were first prepared and characterized. In vitro transscleral study under ultrasound exposure (1MHz, 0.5 W/cm(2), 5 min continuous wave) using isolated sclera of rabbit was performed. The posterior eye segment of rabbit was examined for adverse effect by slit-lamp and histology. It was found that FITC-BSA-SFNs possessed sustained release, bioadhesive, and co-permeation characteristics. The ultrasound application significantly improved the penetration efficiency of FITC-BSA-SFNs as compared with passive delivery, meanwhile caused no damages to the ocular tissue and particles themselves. The distribution profile of SFNs revealed rapid and lasting adhesion on the outer scleral tissues, followed by migration into the interior up to one week after treatment. This research suggested a novel non-invasive transscleral administration of macromolecular protein drugs using SFN carriers combining with ultrasound technology. Copyright © 2014 Elsevier B.V. All rights reserved.
Irreversible Electroporation of Human Primary Uveal Melanoma in Enucleated Eyes
Mandel, Yossi; Laufer, Shlomi; Belkin, Michael; Rubinsky, Boris; Pe'er, Jacob; Frenkel, Shahar
2013-01-01
Uveal melanoma (UM) is the most common primary intraocular tumor in adults and is characterized by high rates of metastatic disease. Although brachytherapy is the most common globe-sparing treatment option for small- and medium-sized tumors, the treatment is associated with severe adverse reactions and does not lead to increased survival rates as compared to enucleation. The use of irreversible electroporation (IRE) for tumor ablation has potential advantages in the treatment of tumors in complex organs such as the eye. Following previous theoretical work, herein we evaluate the use of IRE for uveal tumor ablation in human ex vivo eye model. Enucleated eyes of patients with uveal melanoma were treated with short electric pulses (50–100 µs, 1000–2000 V/cm) using a customized electrode design. Tumor bioimpedance was measured before and after treatment and was followed by histopathological evaluation. We found that IRE caused tumor ablation characterized by cell membrane disruption while sparing the non-cellular sclera. Membrane disruption and loss of cellular capacitance were also associated with significant reduction in total tumor impedance and loss of impedance frequency dependence. The effect was more pronounced near the pulsing electrodes and was dependent on time from treatment to fixation. Future studies should further evaluate the potential of IRE as an alternative method of uveal melanoma treatment. PMID:24039721
In Vitro/In Vivo Evaluation of Dexamethasone--PAMAM Dendrimer Complexes for Retinal Drug Delivery.
Yavuz, Burçin; Pehlivan, Sibel Bozdağ; Vural, İmran; Ünlü, Nurşen
2015-11-01
Current treatment options for diabetic retinopathy (DR) have side effects because of invasive application and topical application does not generally result in therapeutic levels in the target tissue. Therefore, improving the drug delivery to retina, following topical administration, might be a solution to DR treatment problems. The purpose of this study was to investigate the complexation effects of poly(amidoamine) (PAMAM) dendrimers on ocular absorption of dexamethasone (DEX). Using different PAMAM generations, complex formulations were prepared and characterized. Formulations were evaluated in terms of cytotoxicity and cell permeability, as well as ex vivo transport across ocular tissues. The ocular pharmacokinetic properties of DEX formulations were studied in Sprague-Dawley rats following topical and subconjunctival applications, to evaluate the effect of PAMAM on retinal delivery of DEX. Methyl-thiazol-tetrazolium (MTT) assay indicated that all groups resulted in cell viability comparable to DEX solution (87.5%), with the cell viability being the lowest for G3 complex at 73.5%. Transport study results showed that dendrimer complexation increases DEX transport across both cornea and sclera tissues. The results of in vivo studies were also indicated that especially anionic DEX-PAMAM complex formulations have reached higher DEX concentrations in ocular tissues compared with plain DEX suspension. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.
Suprachoroidal Drug Delivery to the Back of the Eye Using Hollow Microneedles
Patel, Samirkumar R.; Lin, Angela S. P.; Edelhauser, Henry F.
2011-01-01
Purpose In this work, we tested the hypothesis that microneedles provide a minimally invasive method to inject particles into the suprachoroidal space for drug delivery to the back of the eye. Methods A single, hollow microneedle was inserted into the sclera, and infused nanoparticle and microparticle suspensions into the suprachoroidal space. Experiments were performed on whole rabbit, pig, and human eyes ex vivo. Particle delivery was imaged using brightfield and fluorescence microscopy as well as microcomputed tomography. Results Microneedles were shown to deliver sulforhodamine B as well as nanoparticle and microparticle suspensions into the suprachoroidal space of rabbit, pig, and human eyes. Volumes up to 35 μL were administered consistently. Optimization of the delivery device parameters showed that microneedle length, pressure, and particle size played an important role in determining successful delivery into the suprachoroidal space. Needle lengths of 800–1,000 μm and applied pressures of 250–300 kPa provided most reliable delivery. Conclusions Microneedles were shown for the first time to deliver nanoparticle and microparticle suspensions into the suprachoroidal space of rabbit, pig and human eyes. This shows that microneedles may provide a minimally invasive method for controlled drug delivery to the back of the eye. PMID:20857178
Kim, Yoo Chun; Oh, Kyung Hee; Edelhauser, Henry F; Prausnitz, Mark R
2015-09-01
In this work, we tested the hypothesis that particles injected into the suprachoroidal space can be localized at the site of injection or broadly distributed throughout the suprachoroidal space by controlling polymeric formulation properties. Single hollow microneedles were inserted into the sclera of New Zealand White rabbits and injected non-biodegradable fluorescently tagged nanoparticles and microparticles suspended in polymeric formulations into the suprachoroidal space of the eye. When formulated in saline, the particles were distributed over 29-42% of the suprachoroidal space immediately after injection. To spread particles over larger areas of the choroidal surface, addition of hyaluronic acid to make moderately non-Newtonian solutions increased particle spread to up to 100% of the suprachoroidal space. To localize particles at the site of injection adjacent to the ciliary body, strongly non-Newtonian polymer solutions localized particles to 8.3-20% of the suprachoroidal space, which exhibited a small increase in area over the course of two months. This study demonstrates targeted particle delivery within the suprachoroidal space using polymer formulations that spread particles over the whole choroidal surface or localized them adjacent to the ciliary body after injection. Copyright © 2015 Elsevier B.V. All rights reserved.
Inoue, Makoto; Abulon, Dina Joy K; Hirakata, Akito
2014-01-01
To compare the effects of different 23- and 25-gauge microincision vitrectomy trocar cannula entry systems on incision architecture. We tested one ridged microvitreoretinal (MVR), one non-ridged MVR, one pointed beveled, and one round-tipped beveled blade (n=10 per blade design per incision type). Each blade's straight and oblique incision architecture was assessed in a silicone disc simulating the sclera. Wound leakage under pressure and endoscopic observations were conducted on sclerotomy sites of isolated porcine eyes (n=4 per blade design) after simulated vitrectomy. Differences in blade design created distinct incision architecture. Incisions were linear with the ridged MVR blade, flattened "M-shaped" with the non-ridged MVR blade, asymmetrical chevron-shaped with the pointed beveled blade, and curved with the round-tipped beveled blade. With the exception of oblique entry incision thickness, both MVR blade designs created thinner incisions than the beveled blades at entry and exit sites. Only the ridged MVR blade created incisions with no leakage. Vitreous incarceration was observed with all trocar cannula systems. Wound closure in porcine eyes was similar with all blades despite differences in incision architecture. Wound leakage occurred at low to moderate infusion pressures with most blades; no wound leakage was observed with ridged MVR blades.
Inoue, Makoto; Abulon, Dina Joy K; Hirakata, Akito
2014-01-01
Purpose To compare the effects of different 23- and 25-gauge microincision vitrectomy trocar cannula entry systems on incision architecture. Methods We tested one ridged microvitreoretinal (MVR), one non-ridged MVR, one pointed beveled, and one round-tipped beveled blade (n=10 per blade design per incision type). Each blade’s straight and oblique incision architecture was assessed in a silicone disc simulating the sclera. Wound leakage under pressure and endoscopic observations were conducted on sclerotomy sites of isolated porcine eyes (n=4 per blade design) after simulated vitrectomy. Results Differences in blade design created distinct incision architecture. Incisions were linear with the ridged MVR blade, flattened “M-shaped” with the non-ridged MVR blade, asymmetrical chevron-shaped with the pointed beveled blade, and curved with the round-tipped beveled blade. With the exception of oblique entry incision thickness, both MVR blade designs created thinner incisions than the beveled blades at entry and exit sites. Only the ridged MVR blade created incisions with no leakage. Vitreous incarceration was observed with all trocar cannula systems. Conclusion Wound closure in porcine eyes was similar with all blades despite differences in incision architecture. Wound leakage occurred at low to moderate infusion pressures with most blades; no wound leakage was observed with ridged MVR blades. PMID:25429201
NASA Astrophysics Data System (ADS)
Mustopa; Susilo, R. S. B.; Arifin; Redhono, D.; Sumandjar, T.
2018-03-01
A 48-years-old man was hospitalized due to febrile for 5 days accompanied by headache and left chest pain radiating into the back. Pain calf, abdominal pain and tea color urine has occured since 1 week before admission. Physical examination revealed temperature 38.5° C, conjungtival suffusion, jaundice sclera, irregularheart sound, hepatomegaly, gastrocnemius tenderness, Faine score 23. Laboratory tests showed leukocytosis, thrombocytopenia, elevated transaminase enzyme, ureum 181 mg/dl, creatinine 4.3 mg/dl, albumin 2.4 g/dl, sodium 110 mmol/L, potassium 2.3 mmol/L, reactive HbsAg, CKMB 68.06 ng/ml, increased HBV-DNA, negative IgM anti Leptospira. MAT demonstrated 4 positive serovar. Electrocardiography revealed AF rapid ventrikel response. Chest x-ray showed cardiomegaly. Abdominal ultrasound revealed hepatomegaly with chronic parenchimal liver disease, renal insuficiency. Fibroscan showed severe fibrosis. Patient was diagnosed with Weil’s disease and hepatorenal syndrome as complication. Patient was given clavulanate amoxicillin injections. This patient was not dialysis, only fluid balance monitoring and checked ureum-creatinine per 3 days, and there was improvement of ureum-creatinine. Hepatorenal syndrome in Weil’s disease contributed to electrolyte imbalance. In addition, chronic hepatitis B on this patient was treated with tenofovir.
Automated choroidal segmentation method in human eye with 1050nm optical coherence tomography
NASA Astrophysics Data System (ADS)
Liu, Cindy; Wang, Ruikang K.
2014-02-01
Choroidal thickness (ChT), defined as the distance between the retinal pigment epithelium (RPE) and the choroid-sclera interface (CSI), is highly correlated with various ocular disorders like high myopia, diabetic retinopathy, and central serous chorioretinopathy. Long wavelength Optical Coherence Tomography (OCT) has the ability to penetrate deep to the CSI, making the measurement of the ChT possible. The ability to accurately segment the CSI and RPE is important in extracting clinical information. However, automated CSI segmentation is challenging due to the weak boundary in the lower choroid and inconsistent texture with varied blood vessels. We propose a K-means clustering based automated algorithm, which is effective in segmenting the CSI and RPE. The performance of the method was evaluated using 531 frames from 4 normal subjects. The RPE and CSI segmentation time was about 0.3 seconds per frame, and the average time was around 0.5 seconds per frame with correction among frames, which is faster than reported algorithms. The results from the proposed method are consistent with the manual segmentation results. Further investigation includes the optimization of the algorithm to cover more OCT images captured from patients and the increase of the processing speed and robustness of the segmentation method.
Interactions of genes and environment in myopia.
Feldkämper, Marita; Schaeffel, Frank
2003-01-01
Myopia is a condition in which the eye is too long for the focal length of cornea and lens, and the plane of sharp focus ends up in front of the retina. Given that the growth of the length of the eye is normally controlled with extreme precision by an image-processing feedback mechanism in the retina, myopia can either be the result of inappropriate visual stimulation, genetically determined changes in the gain or offset of the feedback loops or of inappropriate responses of the target tissues. There is no doubt that an environmental component is involved and extended near work appears to be the major risk factor. However, there is also no doubt that myopia is inherited since myopic parents are much more likely to have myopic children, and myopia is far more frequent in Asian populations than in the USA or Europe, even if groups are compared that have performed similar amounts of near work. A number of systemic or ophthalmic diseases are associated with myopia, indicating that metabolic conditions may interfere either with the gains of the feedback loops or the responses of the target tissue, the sclera. Since there is still no therapy against myopia development, research is directed toward the identification of genes that control the axial elongation of the eye.
Muscarinic cholinergic receptor (M2) plays a crucial role in the development of myopia in mice
Barathi, Veluchamy A.; Kwan, Jia Lin; Tan, Queenie S. W.; Weon, Sung Rhan; Seet, Li Fong; Goh, Liang Kee; Vithana, Eranga N.; Beuerman, Roger W.
2013-01-01
SUMMARY Myopia is a huge public health problem worldwide, reaching the highest incidence in Asia. Identification of susceptible genes is crucial for understanding the biological basis of myopia. In this paper, we have identified and characterized a functional myopia-associated gene using a specific mouse-knockout model. Mice lacking the muscarinic cholinergic receptor gene (M2; also known as Chrm2) were less susceptible to lens-induced myopia compared with wild-type mice, which showed significantly increased axial length and vitreous chamber depth when undergoing experimental induction of myopia. The key findings of this present study are that the sclera of M2 mutant mice has higher expression of collagen type I and lower expression of collagen type V than do wild-type mice and mice that are mutant for other muscarinic subtypes, and, therefore, M2 mutant mice were resistant to the development of experimental myopia. Pharmacological blockade of M2 muscarinic receptor proteins retarded myopia progression in the mouse. These results suggest for the first time a role of M2 in growth-related changes in extracellular matrix genes during myopia development in a mammalian model. M2 receptor antagonists might thus provide a targeted therapeutic approach to the management of this refractive error. PMID:23649821
Pharmaceutical intervention for myopia control
Ganesan, Prema; Wildsoet, Christine F
2010-01-01
Myopia is the result of a mismatch between the optical power and the length of the eye, with the latter being too long. Driving the research in this field is the need to develop myopia treatments that can limit axial elongation. When axial elongation is excessive, as in high myopia, there is an increased risk of visual impairment and blindness due to ensuing pathologies such as retinal detachments. This article covers both clinical studies involving myopic children, and studies involving animal models for myopia. Atropine, a nonselective muscarinic antagonist, has been studied most extensively in both contexts. Because it remains the only drug used in a clinical setting, it is a major focus of the first part of this article, which also covers the many shortcomings of topical ophthalmic atropine. The second part of this article focuses on in vitro and animal-based drug studies, which encompass a range of drug targets including the retina, retinal pigment epithelium and sclera. While the latter studies have contributed to a better understanding of how eye growth is regulated, no new antimyopia drug treatments have reached the clinical setting. Less conservative approaches in research, and in particular, the exploration of new bioengineering approaches for drug delivery, are needed to advance this field. PMID:21258611
Topical anesthesia with benoxinate 0.4% for pterygium surgery.
Frucht-Pery, J
1997-03-01
Anesthesia during pterygium surgery is usually achieved with injections of anesthetic medications. This study evaluated the efficacy of topical anesthesia with benoxinate hydrochloride 0.4% for pterygium surgery. One hundred fifty consecutive patients who had primary or recurrent pterygium underwent surgical excision of the lesion. Before the surgical procedure began, each eye that was operated on received 1 drop of benoxinate hydrochloride 0.4% solution every 1 minute for 10 minutes. The pain sensation was tested with 0.12 forceps. The pterygium was dissected, and 1 or 2 conjunctival sutures were placed, leaving bare sclera. Drops of benoxinate hydrochloride 0.4% were added every 5 minutes during the operation. The average pterygium excision time in this study was 25 minutes. Of the 150 patients studied, only 3 required intraoperative injection of lignocaine 1%. In 2 cases, subconjunctival injection was performed, and in 1 case, retrobulbar injection was required to complete the procedure. Of the remaining 147 patients, 115 had discomfort or mild pain and asked for more anesthetics once or twice during the procedure. Postoperatively, the wounds epithelialized within 7 to 14 days in all patients, except for 2 who had postoperative dellen and 2 who received mitomycin-C postoperatively. Topical administration of benoxinate hydrochloride 0.4% provides useful anesthesia for pterygium surgery.
Persistent inflammatory state after photoreceptor loss in an animal model of retinal degeneration
Noailles, Agustina; Maneu, Victoria; Campello, Laura; Gómez-Vicente, Violeta; Lax, Pedro; Cuenca, Nicolás
2016-01-01
Microglia act as the resident immune cells of the central nervous system, including the retina. In response to damaging stimuli microglia adopt an activated state, which can progress into a phagocytic phenotype and play a potentially harmful role by eliciting the expression and release of pro-inflammatory cytokines. The aim of the present study was to assess longitudinal changes in microglia during retinal degeneration in the homozygous P23H rat, a model of dominant retinitis pigmentosa. Microglial phenotypes, morphology and density were analyzed by immunohistochemistry, flow cytometry, and cytokine antibody array. In addition, we performed electroretinograms to evaluate the retinal response. In the P23H retina, sclera, choroid and ciliary body, inflammatory cells increased in number compared with the control at all ages analyzed. As the rats became older, a higher number of amoeboid MHC-II+ cells were observed in the P23H retina, which correlated with an increase in the expression of pro-inflammatory cytokines. These findings suggest that, in the P23H model, retinal neuroinflammation persists throughout the rat’s life span even after photoreceptor depletion. Therefore, the inclusion of anti-inflammatory drugs at advanced stages of the neurodegenerative process may provide better retinal fitness so the remaining cells could still be used as targets of cellular or gene therapies. PMID:27624537
In vivo operation of the Boston 15-channel wireless subretinal visual prosthesis
NASA Astrophysics Data System (ADS)
Shire, Douglas B.; Doyle, Patrick; Kelly, Shawn K.; Gingerich, Marcus D.; Chen, Jinghua; Cogan, Stuart F.; Drohan, William A.; Mendoza, Oscar; Theogarajan, Luke; Wyatt, John; Rizzo, Joseph F.
2010-02-01
This presentation concerns the engineering development of the Boston visual prosthesis for restoring useful vision to patients blind with degenerative retinal disease. A miniaturized, hermetically-encased, 15-channel wirelessly-operated retinal prosthetic was developed for implantation and pre-clinical studies in Yucatan mini-pig animal models. The prosthesis conforms to the eye and drives a microfabricated polyimide stimulating electrode array having sputtered iridium oxide electrodes. This array is implanted into the subretinal space using a specially-designed ab externo surgical technique; the bulk of the prosthesis is on the surface of the sclera. The implanted device includes a hermetic titanium case containing a 15-channel stimulator chip; secondary power/data receiving coils surround the cornea. Long-term in vitro pulse testing was also performed on the electrodes to ensure their stability over years of operation. Assemblies were first tested in vitro to verify wireless operation of the system in biological saline using a custom RF transmitter circuit and primary coils. Stimulation pulse strength, duration and frequency were programmed wirelessly using a computer with a custom graphical user interface. Operation of the retinal implant was verified in vivo in 3 minipigs for more than three months by measuring stimulus artifacts on the eye surface using contact lens electrodes.
Limbus Impact on Off-angle Iris Degradation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Karakaya, Mahmut; Barstow, Del R; Santos-Villalobos, Hector J
The accuracy of iris recognition depends on the quality of data capture and is negatively affected by several factors such as angle, occlusion, and dilation. Off-angle iris recognition is a new research focus in biometrics that tries to address several issues including corneal refraction, complex 3D iris texture, and blur. In this paper, we present an additional significant challenge that degrades the performance of the off-angle iris recognition systems, called the limbus effect . The limbus is the region at the border of the cornea where the cornea joins the sclera. The limbus is a semitransparent tissue that occludes amore » side portion of the iris plane. The amount of occluded iris texture on the side nearest the camera increases as the image acquisition angle increases. Without considering the role of the limbus effect, it is difficult to design an accurate off-angle iris recognition system. To the best of our knowledge, this is the first work that investigates the limbus effect in detail from a biometrics perspective. Based on results from real images and simulated experiments with real iris texture, the limbus effect increases the hamming distance score between frontal and off-angle iris images ranging from 0.05 to 0.2 depending upon the limbus height.« less
Improved Ocular Delivery of Nepafenac by Cyclodextrin Complexation.
Shelley, Haley; Grant, Makenzie; Smith, Forrest T; Abarca, Eva M; Jayachandra Babu, R
2018-06-13
Nepafenac is a nonsteroidal anti-inflammatory drug (NSAID), currently only available as 0.1% ophthalmic suspension (Nevanac®). This study utilized hydroxypropyl-β-cyclodextrin (HPBCD) to increase the water solubility and trans-corneal permeation of nepafenac. The nepafenac-HPBCD complexation in the liquid and solid states were confirmed by phase solubility, differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and nuclear magnetic resonance spectroscopy (NMR) analyses. Nepafenac 0.1% ophthalmic solution was formulated using HPBCD (same pH and osmolality as that of Nevanac®) and pig eye trans-corneal permeation was studied versus Nevanac®. Furthermore, nepafenac content in cornea, sclera, iris, lens, aqueous humor, choroid, ciliary body, retina, and vitreous humor was studied in a continuous isolated pig eye perfusion model in comparison to the suspension and Nevanac®. Permeation studies using porcine corneas revealed that the solution formulation had a permeation rate 18 times higher than Nevanac®. Furthermore, the solution had 11 times higher corneal retention than Nevanac®. Drug distribution studies using porcine eyes revealed that the solution formulation enables detectable levels in various ocular tissues while the drug was undetectable by Nevanac®. The ocular solution formulation had a significantly higher drug concentration in the cornea compared to the suspension or Nevanac®.
Intracranial Pressure Influences the Behavior of the Optic Nerve Head.
Hua, Yi; Tong, Junfei; Ghate, Deepta; Kedar, Sachin; Gu, Linxia
2017-03-01
In this work, the biomechanical responses of the optic nerve head (ONH) to acute elevations in intracranial pressure (ICP) were systematically investigated through numerical modeling. An orthogonal experimental design was developed to quantify the influence of ten input factors that govern the anatomy and material properties of the ONH on the peak maximum principal strain (MPS) in the lamina cribrosa (LC) and postlaminar neural tissue (PLNT). Results showed that the sensitivity of ONH responses to various input factors was region-specific. In the LC, the peak MPS was most strongly dependent on the sclera thickness, LC modulus, and scleral canal size, whereas in the PLNT, the peak MPS was more sensitive to the scleral canal size, neural tissue modulus, and pia mater modulus. The enforcement of clinically relevant ICP in the retro-orbital subarachnoid space influenced the sensitivity analysis. It also induced much larger strains in the PLNT than in the LC. Moreover, acute elevation of ICP leads to dramatic strain distribution changes in the PLNT, but had minimal impact on the LC. This work could help to better understand patient-specific responses, to provide guidance on biomechanical factors resulting in optic nerve diseases, such as glaucoma, papilledema, and ischemic optic neuropathy, and to illuminate the possibilities for exploiting their potential to treat and prevent ONH diseases.
Mundim, Fabrício M; Antunes, Pedro L; Sousa, Ana Beatriz S; Garcia, Lucas F R; Pires-de-Souza, Fernanda C P
2012-06-01
To evaluate the colour stability of paints used for ocular prosthesis iris painting submitted for accelerated artificial ageing (AAA). Forty specimens of acrylic resin for sclera (16 × 2 mm) were made and separated into eight groups (n = 10) according to the type of paint (gouache, GP; oil, OP; acrylic AP; and composite resin for characterisation, CR) and the colours used (blue/brown). After drying (72 h), a new layer of colourless acrylic resin was applied and the initial colour readout was performed (Spectrophotometer PCB 6807). New colour readouts were performed after AAA, and ΔE was calculated. Statistical analysis (two-way anova-Bonferroni, p < 0.05) demonstrated that the brown colour showed lower ΔE means in comparison with the blue colour, with statistically significant difference for AP only. Blue colour showed no statistically significant difference with regard to the type of paint used. Brown AP showed lower ΔE than the other groups, with significant difference for OP and GP. GP showed greater alteration in ΔE for the brown colour, being statistically similar only to OP. Only the AP group for brown pigment shows clinically acceptable values for colour stability after AAA. © 2011 The Gerodontology Society and John Wiley & Sons A/S.
Lakshminarayanan, Rajamani; Sridhar, Radhakrishnan; Loh, Xian Jun; Nandhakumar, Muruganantham; Barathi, Veluchamy Amutha; Kalaipriya, Madhaiyan; Kwan, Jia Lin; Liu, Shou Ping; Beuerman, Roger Wilmer; Ramakrishna, Seeram
2014-01-01
Topical application of antifungals does not have predictable or well-controlled release characteristics and requires reapplication to achieve therapeutic local concentration in a reasonable time period. In this article, the efficacy of five different US Food and Drug Administration-approved antifungal-loaded (amphotericin B, natamycin, terbinafine, fluconazole, and itraconazole) electrospun gelatin fiber mats were compared. Morphological studies show that incorporation of polyenes resulted in a two-fold increase in fiber diameter and the mats inhibit the growth of yeasts and filamentous fungal pathogens. Terbinafine-loaded mats were effective against three filamentous fungal species. Among the two azole antifungals compared, the itraconazole-loaded mat was potent against Aspergillus strains. However, activity loss was observed for fluconazole-loaded mats against all of the test organisms. The polyene-loaded mats displayed rapid candidacidal activities as well. Biophysical and rheological measurements indicate strong interactions between polyene antifungals and gelatin matrix. As a result, the polyenes stabilized the triple helical conformation of gelatin and the presence of gelatin decreased the hemolytic activity of polyenes. The polyene-loaded fiber mats were noncytotoxic to primary human corneal and sclera fibroblasts. The reduction of toxicity with complete retention of activity of the polyene antifungal-loaded gelatin fiber mats can provide new opportunities in the management of superficial skin infections. PMID:24920895
Microneedle-based drug delivery systems: Microfabrication, drug delivery, and safety
Donnelly, Ryan F.; Raj Singh, Thakur Raghu; Woolfson, A. David
2010-01-01
Many promising therapeutic agents are limited by their inability to reach the systemic circulation, due to the excellent barrier properties of biological membranes, such as the stratum corneum (SC) of the skin or the sclera/cornea of the eye and others. The outermost layer of the skin, the SC, is the principal barrier to topically-applied medications. The intact SC thus provides the main barrier to exogenous substances, including drugs. Only drugs with very specific physicochemical properties (molecular weight < 500 Da, adequate lipophilicity, and low melting point) can be successfully administered transdermally. Transdermal delivery of hydrophilic drugs and macromolecular agents of interest, including peptides, DNA, and small interfering RNA is problematic. Therefore, facilitation of drug penetration through the SC may involve by-pass or reversible disruption of SC molecular architecture. Microneedles (MNs), when used to puncture skin, will by-pass the SC and create transient aqueous transport pathways of micron dimensions and enhance the transdermal permeability. These micropores are orders of magnitude larger than molecular dimensions, and, therefore, should readily permit the transport of hydrophilic macromolecules. Various strategies have been employed by many research groups and pharmaceutical companies worldwide, for the fabrication of MNs. This review details various types of MNs, fabrication methods and, importantly, investigations of clinical safety of MN. PMID:20297904
[Case report of a patient with ochronosis and arthroplasty of the hip and both knees].
Moslavac, Aleksandra; Moslavac, Sasa; Cop, Renata
2003-01-01
Alkaptonuria is a rare hereditary metabolic disorder characterised by absence of the enzyme homogentisic acid oxidase. As a result of this defect homogentisic acid accumulates and is excreted in the urine. The term ochronosis is used to describe bluish-black pigmentation of connective tissue. Ochronotic arthropathy results from the pigmented deposits in the joints of the appendicular and axial skeleton. Findings simulate those of uncomplicated degenerative joint disease, with effusion, articular space narrowing, and bony sclerosis. Our patient is a 70-year old male with ochronotic arthropathy. He has typical ears and sclera discoloration, and had arthroplasty of knees 7 and 4 years ago, respectively. In year 2002, he had undergone total right hip arthroplasty and has been admitted for rehabilitation 14th postoperative day. Individually designed rehabilitation regimen included kinesitherapy, hydrokinesitherapy, and ambulation training with gradual increase in weight bearing exercises and electro-analgesia of associated low back pain. In course of rehabilitation our patient improved his endurance with satisfying range of motion of right hip (flexion 90 degrees, abduction 40 degrees) and strength of hip and thigh musculature. The patient was able to walk with crutches without limitation. We conclude that joint destruction followed by painful locomotion due to ochronotic arthropathy is best treated by total joint arthroplasty, as described in our patient.
Missotten, L; Dirven, W; Van der Schueren, A; Leys, A; De Meester, G; Van Limbergen, E
1998-03-01
We review the results of treatment of small to medium-sized choroidal malignant melanomas after high-dose-rate brachytherapy with a strontium-90 applicator. The applicator is positioned against the sclera using an afterloading technique. Brachytherapy is completed in a single session lasting 2-4 h with the patient under local anaesthesia. From September 1983 until March 1995, 46 eyes were treated in this way. Most tumours were 7-11 mm in diameter (range from 4.5-15 mm) with a mean height of approximately 3 mm (range from 1.5-7 mm). Follow-up ranged from 6 months to 12 years (mean 49 months). Thirty of the 46 eyes had at the final evaluation a nonevolutive scar (20 of these after a single application, the others with some additional treatment). In 13 eyes the tumours were in involution but their complete destruction was not yet certain, and 3 eyes were enucleated for local recurrence. Three patients developed systemic metastases. No radiogenic complications were noticed. Strontium-90 brachytherapy is a valuable and safe treatment technique for small to medium-sized choroidal malignant melanomas. In addition the use of a strontium-90 applicator is inexpensive thanks to this element's long half-life and the short application time.
Perineurial-like Cells and EMA Expression in the Suprachoroidal Region of the Human Eye.
Gilbert, Andrea R; Chévez-Barrios, Patricia; Cykowski, Matthew D
2018-05-01
The suprachoroidal region of the eye comprises vascular channels, melanocytes, and thin fibroblasts with elongated cytoplasm that are positioned directly adjacent to the densely collagenous sclera. Morphological similarities between these suprachoroidal fibroblasts and arachnoid cells and perineurial cells have been recognized, but whether these fibroblasts have a perineurial cell-like immunophenotype is not known. To further examine the relationship of these three cell types, we investigated the comparative expression of epithelial membrane antigen (EMA), the tight junction protein claudin-1, glucose transporter-1 (Glut-1), and CD34 in suprachoroidal fibroblasts, arachnoid of the optic nerve sheath, and perineurium of ciliary nerves in eight human eye specimens. Granular, diffuse, and cytoplasmic EMA expression was seen in suprachoroidal fibroblasts, but this was not contiguous with the similar pattern of EMA expression in adjacent perineurium and arachnoid. CD34 expression in suprachoroidal fibroblasts was also seen, similar to arachnoid and perineurium. Claudin-1 and Glut-1 were not consistently expressed in suprachoroidal fibroblasts, distinguishing them from perineurial cells in particular and suggesting that these fibroblasts do not arise directly from adjacent arachnoid or perineurium. Nonetheless, the overlapping morphology and protein expression suggest phenotypic similarities in these cells that protect and support adjacent retina, optic nerve, and peripheral nerve.
Comparison of Six Different Silicones In Vitro for Application as Glaucoma Drainage Device
Windhövel, Claudia; Harder, Lisa; Bach, Jan-Peter; Teske, Michael; Grabow, Niels; Eickner, Thomas; Chichkov, Boris; Nolte, Ingo
2018-01-01
Silicones are widely used in medical applications. In ophthalmology, glaucoma drainage devices are utilized if conservative therapies are not applicable or have failed. Long-term success of these devices is limited by failure to control intraocular pressure due to fibrous encapsulation. Therefore, different medical approved silicones were tested in vitro for cell adhesion, cell proliferation and viability of human Sclera (hSF) and human Tenon fibroblasts (hTF). The silicones were analysed also depending on the sample preparation according to the manufacturer’s instructions. The surface quality was characterized with environmental scanning electron microscope (ESEM) and water contact angle measurements. All silicones showed homogeneous smooth and hydrophobic surfaces. Cell adhesion was significantly reduced on all silicones compared to the negative control. Proliferation index and cell viability were not influenced much. For development of a new glaucoma drainage device, the silicones Silbione LSR 4330 and Silbione LSR 4350, in this study, with low cell counts for hTF and low proliferation indices for hSF, and silicone Silastic MDX4-4210, with low cell counts for hSF and low proliferation indices for hTF, have shown the best results in vitro. Due to the high cell adhesion shown on Silicone LSR 40, 40,026, this material is unsuitable. PMID:29495462
Probabilistic Modeling Of Ocular Biomechanics In VIIP: Risk Stratification
NASA Technical Reports Server (NTRS)
Feola, A.; Myers, J. G.; Raykin, J.; Nelson, E. S.; Mulugeta, L.; Samuels, B.; Ethier, C. R.
2016-01-01
Visual Impairment and Intracranial Pressure (VIIP) syndrome is a major health concern for long-duration space missions. Currently, it is thought that a cephalad fluid shift in microgravity causes elevated intracranial pressure (ICP) that is transmitted along the optic nerve sheath (ONS). We hypothesize that this in turn leads to alteration and remodeling of connective tissue in the posterior eye which impacts vision. Finite element (FE) analysis is a powerful tool for examining the effects of mechanical loads in complex geometries. Our goal is to build a FE analysis framework to understand the response of the lamina cribrosa and optic nerve head to elevations in ICP in VIIP. To simulate the effects of different pressures on tissues in the posterior eye, we developed a geometric model of the posterior eye and optic nerve sheath and used a Latin hypercubepartial rank correlation coef-ficient (LHSPRCC) approach to assess the influence of uncertainty in our input parameters (i.e. pressures and material properties) on the peak strains within the retina, lamina cribrosa and optic nerve. The LHSPRCC approach was repeated for three relevant ICP ranges, corresponding to upright and supine posture on earth, and microgravity [1]. At each ICP condition we used intraocular pressure (IOP) and mean arterial pressure (MAP) measurements of in-flight astronauts provided by Lifetime Surveillance of Astronaut Health Program, NASA Johnson Space Center. The lamina cribrosa, optic nerve, retinal vessel and retina were modeled as linear-elastic materials, while other tissues were modeled as a Mooney-Rivlin solid (representing ground substance, stiffness parameter c1) with embedded collagen fibers (stiffness parameters c3, c4 and c5). Geometry creationmesh generation was done in Gmsh [2], while FEBio was used for all FE simulations [3]. The LHSPRCC approach resulted in correlation coefficients in the range of 1. To assess the relative influence of the uncertainty in an input parameter on the peak strains, we ranked and then normalized these coefficients, considering that normalized values 0.5 implied a substantial influence on the range of the peak strains in the optic nerve head (ONH). IOP and ICP were found to have a major influence on the peak strains in the ONH, as did optic nerve and LC stiffness. Interestingly, the stiffness of the sclera far from the scleral canal did not have a large influence on peak strains in ONH tissues; however, the collagen fiber stiffness in the peripapillary sclera and annular ring both influenced the peak strains within the ONH. We have created a physiologically relevant model that incorporated collagen fibers to study the effects of elevated ICP. Elevated ICP resulted in strains in the optic nerve that are not predicted to occur on earth: the upright or supine conditions. We found that IOP, ICP, lamina cribrosa stiffness and optic nerve stiffness had the highest association with these extreme strains in the ONH. These extreme strains may activate mechanosensitive cells that induce tissue remodeling and are a risk factor for the development of VIIP.
The effect of intravitreal injection of vehicle solutions on form deprivation myopia in tree shrews.
Ward, Alexander H; Siegwart, John T; Frost, Michael R; Norton, Thomas T
2016-04-01
lntravitreal injection of substances dissolved in a vehicle solution is a common tool used to assess retinal function. We examined the effect of injection procedures (three groups) and vehicle solutions (four groups) on the development of form deprivation myopia (FDM) in juvenile tree shrews, mammals closely related to primates, starting at 24 days of visual experience (about 45 days of age). In seven groups (n = 7 per group), the myopia produced by monocular form deprivation (FD) was measured daily for 12 days during an 11-day treatment period. The FD eye was randomly selected; the contralateral eye served as an untreated control. The refractive state of both eyes was measured daily, starting just before FD began (day 1); axial component dimensions were measured on day 1 and after eleven days of treatment (day 12). Procedure groups: the myopia (treated eye - control eye refraction) in the FD group was the reference. The sham group only underwent brief daily anesthesia and opening of the conjunctiva to expose the sclera. The puncture group, in addition, had a pipette inserted daily into the vitreous. In four vehicle groups, 5 μL of vehicle was injected daily. The NaCl group received 0.85% NaCl. In the NaCl + ascorbic acid group, 1 mg/mL of ascorbic acid was added. The water group received sterile water. The water + ascorbic acid group received water with ascorbic acid (1 mg/mL). We found that the procedures associated with intravitreal injections (anesthesia, opening of the conjunctiva, and puncture of the sclera) did not significantly affect the development of FDM. However, injecting 5 μL of any of the four vehicle solutions slowed the development of FDM. NaCl had a small effect; myopia development in the last 6 days (-0.15 ± 0.08 D/day) was significantly less than in the FD group (-0.55 ± 0.06 D/day). NaCl + Ascorbic acid further slowed the development of FDM on several treatment days. H2O (-0.09 ± 0.05 D/day) and H2O + ascorbic acid (-0.08 ± 0.05 D/day) both almost completely blocked myopia development. The treated eye vitreous chamber elongation, compared with the control eye, in all groups was consistent with the amount of myopia. When FD continued (days 12-16) without injections in the water and water + ascorbic acid groups, the rate of myopia development quickly increased. Thus, it appears the vehicles affected retinal signaling rather than causing damage. The effect of water and water + ascorbic acid may be due to reduced osmolality or ionic concentration near the tip of the injection pipette. The effect of ascorbic acid, compared to NaCl alone, may be due to its reported dopaminergic activity. Copyright © 2016 Elsevier Ltd. All rights reserved.
Retinotomy using an erbium:YAG laser on human autopsy eyes
NASA Astrophysics Data System (ADS)
Ellsworth, Lansing G.; Kramer, Theresa R.; Noecker, Robert J.; Snyder, Robert W.; Yarborough, J. Michael
1994-06-01
Mid-IR lasers that operate near the absorption peak of water have a short penetration depth in ocular tissues. Ablation of tissue can be accomplished with minimal coagulative damage to underlying structures. We used an erbium:YAG laser equipped with a contact probe to create retinotomy sites in the human retina of eye bank eyes. An erbium:YAG laser (2.94 micrometers ) equipped with an infrared transmitting glass fiber and a sapphire tip (400 micrometers ) was used to directly ablate the surface of the retina. We administered both single and multiple pulses to the macula and peripheral retina using energy levels from 4 to 16 mJ per pulse. The retinas were then examined histopathologically to evaluate the extent of ablation and coagulative damage. Single pulses at low energy levels were noted to cause ablative damage to the nerve fiber layer and ganglion cell layer without a notable coagulative effect. The mean ablation depth at lower energy levels was less than the mean ablation depth at higher energy levels. Extensive laser application produced disruption of the retinal pigment epithelium, choroid and sclera. the erbium:YAG laser equipped with a contact probe is an effective means of creating retinotomies in human autopsy eyes. When used in the single pulse mode at lower energy levels, the erbium:YAG laser appears capable of removing superficial retinal layers without damaging deeper structures.
An Ilomastat-CD Eye Drop Formulation to Treat Ocular Scarring.
Mohamed-Ahmed, Abeer H A; Lockwood, Alastair; Li, He; Bailly, Maryse; Khaw, Peng T; Brocchini, Steve
2017-07-01
The purpose of this study was to develop a topical matrix metalloproteinase inhibitor preparation for antiscarring therapy. The broad spectrum matrix metalloproteinase inhibitor ilomastat was formulated using 2-hydroxypropyl-β-cyclodextrin in aqueous solution. In vitro activity of ilomastat-cyclodextrin (ilomastat-CD) was examined using fibroblasts seeded in collagen. Permeation of ilomastat-CD eye drop through pig eye conjunctiva was confirmed using Franz diffusion cells. Ilomastat-CD eye drop was applied to rabbit eyes in vivo, and the distribution of ilomastat in ocular tissues and fluids was determined by liquid chromatography-mass spectroscopy. The aqueous solubility of ilomastat-CD was ∼1000 μg/mL in water and 1400 μg/mL in PBS (pH 7.4), which is greater than ilomastat alone (140 and 160 μg/mL in water and PBS, respectively). The in vitro activity of ilomastat-CD to inhibit collagen contraction in the presence of human Tenon fibroblast cells was unchanged compared to uncomplexed ilomastat. Topically administered ilomastat-CD in vivo to rabbit eyes resulted in a therapeutic concentration of ilomastat being present in the sclera and conjunctiva and within the aqueous humor. Ilomastat-CD has the potential to be formulated as an eye drop for use as an antifibrotic, which may have implications for the prevention of scarring in many settings, for example glaucoma filtration surgery.
MLL2 mutation detection in 86 patients with Kabuki syndrome: a genotype-phenotype study.
Makrythanasis, P; van Bon, B W; Steehouwer, M; Rodríguez-Santiago, B; Simpson, M; Dias, P; Anderlid, B M; Arts, P; Bhat, M; Augello, B; Biamino, E; Bongers, E M H F; Del Campo, M; Cordeiro, I; Cueto-González, A M; Cuscó, I; Deshpande, C; Frysira, E; Izatt, L; Flores, R; Galán, E; Gener, B; Gilissen, C; Granneman, S M; Hoyer, J; Yntema, H G; Kets, C M; Koolen, D A; Marcelis, C l; Medeira, A; Micale, L; Mohammed, S; de Munnik, S A; Nordgren, A; Psoni, S; Reardon, W; Revencu, N; Roscioli, T; Ruiterkamp-Versteeg, M; Santos, H G; Schoumans, J; Schuurs-Hoeijmakers, J H M; Silengo, M C; Toledo, L; Vendrell, T; van der Burgt, I; van Lier, B; Zweier, C; Reymond, A; Trembath, R C; Perez-Jurado, L; Dupont, J; de Vries, B B A; Brunner, H G; Veltman, J A; Merla, G; Antonarakis, S E; Hoischen, A
2013-12-01
Recently, pathogenic variants in the MLL2 gene were identified as the most common cause of Kabuki (Niikawa-Kuroki) syndrome (MIM#147920). To further elucidate the genotype-phenotype correlation, we studied a large cohort of 86 clinically defined patients with Kabuki syndrome (KS) for mutations in MLL2. All patients were assessed using a standardized phenotype list and all were scored using a newly developed clinical score list for KS (MLL2-Kabuki score 0-10). Sequencing of the full coding region and intron-exon boundaries of MLL2 identified a total of 45 likely pathogenic mutations (52%): 31 nonsense, 10 missense and four splice-site mutations, 34 of which were novel. In five additional patients, novel, i.e. non-dbSNP132 variants of clinically unknown relevance, were identified. Patients with likely pathogenic nonsense or missense MLL2 mutations were usually more severely affected (median 'MLL2-Kabuki score' of 6) as compared to the patients without MLL2 mutations (median 'MLL2-Kabuki score' of 5), a significant difference (p < 0.0014). Several typical facial features such as large dysplastic ears, arched eyebrows with sparse lateral third, blue sclerae, a flat nasal tip with a broad nasal root, and a thin upper and a full lower lip were observed more often in mutation positive patients. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Unconventional Aqueous Humor Outflow: A Review
Johnson, Mark; McLaren, Jay W.; Overby, Darryl R.
2016-01-01
Aqueous humor flows out of the eye primarily through the conventional outflow pathway that includes the trabecular meshwork and Schlemm's canal. However, a fraction of aqueous humor passes through an alternative or ‘unconventional’ route that includes the ciliary muscle, supraciliary and suprachoroidal spaces. From there, unconventional outflow may drain through two pathways: a uveoscleral pathway where aqueous drains across the sclera to be resorbed by orbital vessels, and a uveovortex pathway where aqueous humor enters the choroid to drain through the vortex veins. We review the anatomy, physiology and pharmacology of these pathways. We also discuss methods to determine unconventional outflow rate, including direct techniques that use radioactive or fluorescent tracers recovered from tissues in the unconventional pathway and indirect methods that estimate unconventional outflow based on total outflow over a range of pressures. Indirect methods are subject to a number of assumptions and generally give poor agreement with tracer measurements. We review the variety of animal models that have been used to study conventional and unconventional outflow. The mouse appears to be a promising model because it captures several aspects of conventional and unconventional outflow dynamics common to humans, although questions remain regarding the magnitude of unconventional outflow in mice. Finally, we review future directions. There is a clear need to develop improved methods for measuring unconventional outflow in both animals and humans. PMID:26850315
Contribution by Departments of Forensic Medicine to Tissue Donation for Transplant Purposes.
Malm, Torsten; Sandgren Åkerman, Åsa; Greby, Jesper; Odö, Björn; Henriksson, Bengt-Åke
2016-12-01
A department of forensic medicine (DFM) can be a valuable source for tissue donation, but logistics can prove difficult to overcome as it pertains to obtaining tissues for donation. This article describes the potential of tissues that can be procured for transplantation. Sweden has 9.7 million inhabitants, with an annual mortality rate of 90 000 and 5500 medicolegal autopsies per year. Cooperation between tissue banking and 2 DFMs began in the mid-1980s. Recently, cooperation has expanded to include all six DFMs. All tissue establishments (TEs) were asked to complete a questionnaire concerning their cooperation with DFMs from 2011 through 2013. A total of 298 actual donors were identified; 1090 tissues were procured including cardiovascular tissue, cornea, sclera, ear bones, and skin for transplantation. Of the tissues distributed, 553 were for transplantation and 72 for other medical purposes. Twenty-three percent of the tissues were discarded. Reasons for tissue rejection included deficient tissue quality (65%), positive serology tests (9%), positive bacteriology tests after decontamination procedures (7%), technical errors (<1%), and other reasons (18%). Nineteen percent of all tissues distributed for transplantation came from donors in DFMs. The cooperation between DFMs and TEs was described as well functioning and excellent. Education and national courses in tissue procurement for employees in DFMs are contributing factors to such positive interactions. The support from the National Board of Forensic Medicine is an important factor for sustainable progress.
Miyazawa, Arata; Hong, Young-Joo; Makita, Shuichi; Kasaragod, Deepa; Yasuno, Yoshiaki
2017-01-01
Jones matrix-based polarization sensitive optical coherence tomography (JM-OCT) simultaneously measures optical intensity, birefringence, degree of polarization uniformity, and OCT angiography. The statistics of the optical features in a local region, such as the local mean of the OCT intensity, are frequently used for image processing and the quantitative analysis of JM-OCT. Conventionally, local statistics have been computed with fixed-size rectangular kernels. However, this results in a trade-off between image sharpness and statistical accuracy. We introduce a superpixel method to JM-OCT for generating the flexible kernels of local statistics. A superpixel is a cluster of image pixels that is formed by the pixels’ spatial and signal value proximities. An algorithm for superpixel generation specialized for JM-OCT and its optimization methods are presented in this paper. The spatial proximity is in two-dimensional cross-sectional space and the signal values are the four optical features. Hence, the superpixel method is a six-dimensional clustering technique for JM-OCT pixels. The performance of the JM-OCT superpixels and its optimization methods are evaluated in detail using JM-OCT datasets of posterior eyes. The superpixels were found to well preserve tissue structures, such as layer structures, sclera, vessels, and retinal pigment epithelium. And hence, they are more suitable for local statistics kernels than conventional uniform rectangular kernels. PMID:29082073
Full-field OCT: applications in ophthalmology
NASA Astrophysics Data System (ADS)
Grieve, Kate; Dubois, Arnaud; Paques, Michel; Le Gargasson, Jean-Francois; Boccara, Albert C.
2005-04-01
We present images of ocular tissues obtained using ultrahigh resolution full-field OCT. The experimental setup is based on the Linnik interferometer, illuminated by a tungsten halogen lamp. En face tomographic images are obtained in real-time without scanning by computing the difference of two phase-opposed interferometric images recorded by a high-resolution CCD camera. A spatial resolution of 0.7 μm × 0.9 μm (axial × transverse) is achieved thanks to the short source coherence length and the use of high numerical aperture microscope objectives. A detection sensitivity of 90 dB is obtained by means of image averaging and pixel binning. Whole unfixed eyes and unstained tissue samples (cornea, lens, retina, choroid and sclera) of ex vivo rat, mouse, rabbit and porcine ocular tissues were examined. The unprecedented resolution of our instrument allows cellular-level resolution in the cornea and retina, and visualization of individual fibers in the lens. Transcorneal lens imaging was possible in all animals, and in albino animals, transscleral retinal imaging was achieved. We also introduce our rapid acquisition full-field optical coherence tomography system designed to accommodate in vivo ophthalmologic imaging. The variations on the original system technology include the introduction of a xenon arc lamp as source, and rapid image acquisition performed by a high-speed CMOS camera, reducing acquisition time to 5 ms per frame.
Transverse depth-dependent changes in corneal collagen lamellar orientation and distribution
Abass, Ahmed; Hayes, Sally; White, Nick; Sorensen, Thomas; Meek, Keith M.
2015-01-01
It is thought that corneal surface topography may be stabilized by the angular orientation of out-of plane lamellae that insert into the anterior limiting membrane. In this study, micro-focus X-ray scattering data were used to obtain quantitative information about lamellar inclination (with respect to the corneal surface) and the X-ray scatter intensity throughout the depth of the cornea from the centre to the temporal limbus. The average collagen inclination remained predominantly parallel to the tissue surface at all depths. However, in the central cornea, the spread of inclination angles was greatest in the anterior-most stroma (reflecting the increased lamellar interweaving in this region), and decreased with tissue depth; in the peripheral cornea inclination angles showed less variation throughout the tissue thickness. Inclination angles in the deeper stroma were generally higher in the peripheral cornea, suggesting the presence of more interweaving in the posterior stroma away from the central cornea. An increase in collagen X-ray scatter was identified in a region extending from the sclera anteriorly until about 2 mm from the corneal centre. This could arise from the presence of larger diameter fibrils, probably of scleral origin, which are known to exist in this region. Incorporation of this quantitative information into finite-element models will further improve the accuracy with which they can predict the biomechanical response of the cornea to pathology and refractive procedures. PMID:25631562
Computed Tomography and Magnetic Resonance Anatomy of the Normal Orbit and Eye of the Horse.
D'Août, C; Nisolle, J F; Navez, M; Perrin, R; Launois, T; Brogniez, L; Clegg, P; Hontoir, F; Vandeweerd, J M
2015-10-01
Traumatic and infectious diseases of the eye and orbit can occur in horses. For diagnosis and monitoring of such diseases, medical imaging is useful including computed tomography (CT) and magnetic resonance imaging (MRI). The aim of the current study was to describe CT and MRI anatomy of the equine orbit and ocular globe. The heads from four adult horses were scanned with a 6-slice Emotion 6 CT (Siemens, Erlangen), and a 3.0 Tesla Siemens Verio 6 MRI using T1 and T2-weighted sequences. To validate CT and MR reference images, these were compared with anatomical models and gross anatomical sections. The bony limits of the orbital cavity, the relationship of the orbit with sinuses and foramina of the skull were well identified by CT. MRI was useful to observe soft tissues and was able to identify adnexae of the ocular globe (eyelids, periorbital fat, extraocular muscles, lacrymal and tarsal glands). Although MRI was able to identify all components of the eye (including the posterior chamber), it could not differentiate sclera from choroid and retina. The only nerve identified was the optic nerve. Vessels were not seen in this series of cadaver heads. This study showed that CT and MRI are useful techniques to image the equine orbit and eye that can have clinical applications. © 2014 Blackwell Verlag GmbH.
A stereotaxic method of recording from single neurons in the intact in vivo eye of the cat.
Molenaar, J; Van de Grind, W A
1980-04-01
A method is described for recording stereotaxically from single retinal neurons in the optically intact in vivo eye of the cat. The method is implemented with the help of a new type of stereotaxic instrument and a specially developed stereotaxic atlas of the cat's eye and retina. The instrument is extremely stable and facilitates intracellular recording from retinal neurons. The microelectrode can be rotated about two mutually perpendicular axes, which intersect in the freely positionable pivot point of the electrode manipulation system. When the pivot point is made to coincide with a small electrode-entrance hole in the sclera of the eye, a large retinal region can be reached through this fixed hole in the immobilized eye. The stereotaxic method makes it possible to choose a target point on the presented eye atlas and predict the settings of the instrument necessary to reach this target. This method also includes the prediction of the corresponding light stimulus position on a tangent screen and the calculation of the projection of the recording electrode on this screen. The sources of error in the method were studied experimentally and a numerical perturbation analysis was carried out to study the influence of each of the sources of error on the final result. The overall accuracy of the method is of the order of 5 degrees of visual angle, which will be sufficient for most purposes.
Ichien, K; Yamamoto, T; Kitazawa, Y; Oguri, A; Ando, H; Kondo, Y
1997-01-01
To determine whether a new, reversible thermosetting gel enhances mitomycin C transfer to target ocular tissues in the rabbit eye. A 0.1 ml solution of mitomycin C containing 0.22 microgram, 2.9 micrograms, or 28 micrograms of the agent dissolved in a reversible thermosetting gel consisting of methylcellulose, citric acid, and polyethylene glycol was injected subconjunctivally in 30 New Zealand albino rabbits. Scleral and conjunctival tissues were excised at 0.5, 1, 2, 4, or 24 hours after the injection and mitomycin C concentrations in these tissues were determined by high performance liquid chromatography. The concentration over time was approximated to a single exponential curve, and initial mitomycin C concentrations, time constants, and half life values were determined. Finally, the areas under the curves (AUCs) between 0.5 and 24 hours were calculated. The mitomycin C concentrations in the target tissues were dose dependent and decreased rapidly over 24 hours. Both the initial mitomycin C concentrations as well as AUCs in these eyes treated with mitomycin C, dissolved in a reversible thermosetting gel, were higher than those in eyes treated similarly in a previous study in which the gel was not used. Applied subconjunctivally in the rabbit eye, mitomycin C dissolved in the reversible thermosetting gel enhanced transfer of the agent to the sclera and the conjunctiva.
Guidance of retinal axons in mammals.
Herrera, Eloísa; Erskine, Lynda; Morenilla-Palao, Cruz
2017-11-26
In order to navigate through the surrounding environment many mammals, including humans, primarily rely on vision. The eye, composed of the choroid, sclera, retinal pigmented epithelium, cornea, lens, iris and retina, is the structure that receives the light and converts it into electrical impulses. The retina contains six major types of neurons involving in receiving and modifying visual information and passing it onto higher visual processing centres in the brain. Visual information is relayed to the brain via the axons of retinal ganglion cells (RGCs), a projection known as the optic pathway. The proper formation of this pathway during development is essential for normal vision in the adult individual. Along this pathway there are several points where visual axons face 'choices' in their direction of growth. Understanding how these choices are made has advanced significantly our knowledge of axon guidance mechanisms. Thus, the development of the visual pathway has served as an extremely useful model to reveal general principles of axon pathfinding throughout the nervous system. However, due to its particularities, some cellular and molecular mechanisms are specific for the visual circuit. Here we review both general and specific mechanisms involved in the guidance of mammalian RGC axons when they are traveling from the retina to the brain to establish precise and stereotyped connections that will sustain vision. Copyright © 2017 Elsevier Ltd. All rights reserved.
Jones, H. J.; Girard, M. J.; White, N.; Fautsch, M. P.; Morgan, J. E.; Ethier, C. R.; Albon, J.
2015-01-01
The aim of this study was to quantify connective tissue fibre orientation and alignment in young, old and glaucomatous human optic nerve heads (ONH) to understand ONH microstructure and predisposition to glaucomatous optic neuropathy. Transverse (seven healthy, three glaucomatous) and longitudinal (14 healthy) human ONH cryosections were imaged by both second harmonic generation microscopy and small angle light scattering (SALS) in order to quantify preferred fibre orientation (PFO) and degree of fibre alignment (DOFA). DOFA was highest within the peripapillary sclera (ppsclera), with relatively low values in the lamina cribrosa (LC). Elderly ppsclera DOFA was higher than that in young ppsclera (p < 0.00007), and generally higher than in glaucoma ppsclera. In all LCs, a majority of fibres had preferential orientation horizontally across the nasal–temporal axis. In all glaucomatous LCs, PFO was significantly different from controls in a minimum of seven out of 12 LC regions (p < 0.05). Additionally, higher fibre alignment was observed in the glaucomatous inferior–temporal LC (p < 0.017). The differences between young and elderly ONH fibre alignment within regions suggest that age-related microstructural changes occur within the structure. The additional differences in fibre alignment observed within the glaucomatous LC may reflect an inherent susceptibility to glaucomatous optic neuropathy, or may be a consequence of ONH remodelling and/or collapse. PMID:25808336
Density of ocular components of the bovine eye.
Su, Xiao; Vesco, Christina; Fleming, Jacquelyn; Choh, Vivian
2009-10-01
Density is essential for acoustic characterization of tissues and provides a basic input for ultrasound backscatter and absorption models. Despite the existence of extensive compilations of acoustic properties, neither unified data on ocular density nor comparisons of the densities between all ocular components can be found. This study was undertaken to determine the mass density of all the ocular components of the bovine eye. Liquid components were measured through mass/volume ratio, whereas solid tissues were measured with two different densitometry techniques based on Archimedes Principle. The first method determines the density by measuring dry and wet weight of the tissues. The second method consists of immersing the tissues in sucrose solutions of varying densities and observing their buoyancy. Although the mean densities for all tissues were found to be within 0.02 g/cm by both methods, only the sucrose solution method offered a consistent relative order for all measured ocular components, as well as a considerably smaller standard deviation (a maximum standard deviation of 0.004 g/cm for cornea). The lens was found to be the densest component, followed by the sclera, cornea, choroid, retina, aqueous, and vitreous humors. The consistent results of the sucrose solution tests suggest that the ocular mass density is a physical property that is more dependent on the compositional and structural characteristics of the tissue and than on population variability.
Jones, H J; Girard, M J; White, N; Fautsch, M P; Morgan, J E; Ethier, C R; Albon, J
2015-05-06
The aim of this study was to quantify connective tissue fibre orientation and alignment in young, old and glaucomatous human optic nerve heads (ONH) to understand ONH microstructure and predisposition to glaucomatous optic neuropathy. Transverse (seven healthy, three glaucomatous) and longitudinal (14 healthy) human ONH cryosections were imaged by both second harmonic generation microscopy and small angle light scattering (SALS) in order to quantify preferred fibre orientation (PFO) and degree of fibre alignment (DOFA). DOFA was highest within the peripapillary sclera (ppsclera), with relatively low values in the lamina cribrosa (LC). Elderly ppsclera DOFA was higher than that in young ppsclera (p < 0.00007), and generally higher than in glaucoma ppsclera. In all LCs, a majority of fibres had preferential orientation horizontally across the nasal-temporal axis. In all glaucomatous LCs, PFO was significantly different from controls in a minimum of seven out of 12 LC regions (p < 0.05). Additionally, higher fibre alignment was observed in the glaucomatous inferior-temporal LC (p < 0.017). The differences between young and elderly ONH fibre alignment within regions suggest that age-related microstructural changes occur within the structure. The additional differences in fibre alignment observed within the glaucomatous LC may reflect an inherent susceptibility to glaucomatous optic neuropathy, or may be a consequence of ONH remodelling and/or collapse.
Vupparaboina, Kiran Kumar; Nizampatnam, Srinath; Chhablani, Jay; Richhariya, Ashutosh; Jana, Soumya
2015-12-01
A variety of vision ailments are indicated by anomalies in the choroid layer of the posterior visual section. Consequently, choroidal thickness and volume measurements, usually performed by experts based on optical coherence tomography (OCT) images, have assumed diagnostic significance. Now, to save precious expert time, it has become imperative to develop automated methods. To this end, one requires choroid outer boundary (COB) detection as a crucial step, where difficulty arises as the COB divides the choroidal granularity and the scleral uniformity only notionally, without marked brightness variation. In this backdrop, we measure the structural dissimilarity between choroid and sclera by structural similarity (SSIM) index, and hence estimate the COB by thresholding. Subsequently, smooth COB estimates, mimicking manual delineation, are obtained using tensor voting. On five datasets, each consisting of 97 adult OCT B-scans, automated and manual segmentation results agree visually. We also demonstrate close statistical match (greater than 99.6% correlation) between choroidal thickness distributions obtained algorithmically and manually. Further, quantitative superiority of our method is established over existing results by respective factors of 27.67% and 76.04% in two quotient measures defined relative to observer repeatability. Finally, automated choroidal volume estimation, being attempted for the first time, also yields results in close agreement with that of manual methods. Copyright © 2015 Elsevier Ltd. All rights reserved.
Toscano-Garibay, Julia Dolores; Quiroz-Mercado, Hugo; Espitia-Pinzón, Clara; Gil-Carrasco, Félix; Flores-Estrada, José Javier
2014-01-01
Cryotherapy is a no invasive technique that uses intense cold to freeze and destroy cancer tissues. There are no descriptions of its effects over the expression of vascular endothelial growth factor and pigment epithelium-derived factor. Experimental study in cryogenic spot were applied in the right sclera of twelve pigs for ten minutes. Other 3 pigs were used as normal controls. Animals were sacrificed at 7, 14 and 21 and the tissues of choriodes and retina were dissected in areas of approximately 1 cm2 surrounding cryogenic spots. Expression levels of vascular endothelial growth factor and pigment epithelium-derived factor were determined analyzed using polymerase chain reaction coupled to reverse-transcription. Vascular endothelial growth factor was significantly downregulated (24%, p< 0.05) seven days post-treatment meanwhile pigment epithelium-derived factor levels increased 44.8% (p< 0.05) as compared to normal controls (untreated). Both vascular endothelial growth factor and pigment epithelium-derived factor levels remain the same until day 14 but returned to basal expression at day 21. This work expose the relation of cryotherapy with the expression of two factors related to angiogenesis. RESULTS showed significant changes on the expression of vascular endothelial growth factor and pigment epithelium-derived factor illustrating that both proteins are regulated in response to cryogenic treatment in relatively short periods (21 days).
A surgical simulator for peeling the inner limiting membrane during wet conditions.
Omata, Seiji; Someya, Yusei; Adachi, Shyn'ya; Masuda, Taisuke; Hayakawa, Takeshi; Harada, Kanako; Mitsuishi, Mamoru; Totsuka, Kiyohito; Araki, Fumiyuki; Takao, Muneyuki; Aihara, Makoto; Arai, Fumihito
2018-01-01
The present study was performed to establish a novel ocular surgery simulator for training in peeling of the inner limited membrane (ILM). This simulator included a next-generation artificial ILM with mechanical properties similar to the natural ILM that could be peeled underwater in the same manner as in actual surgery. An artificial eye consisting of a fundus and eyeball parts was fabricated. The artificial eye was installed in the eye surgery simulator. The fundus part was mounted in the eyeball, which consisted of an artificial sclera, retina, and ILM. To measure the thickness of the fabricated ILM on the artificial retina, we calculated the distance of the step height as the thickness of the artificial ILM. Two experienced ophthalmologists then assessed the fabricated ILM by sensory evaluation. The minimum thickness of the artificial ILM was 1.9 ± 0.3 μm (n = 3). We were able to perform the peeling task with the ILM in water. Based on the sensory evaluation, an ILM with a minimum thickness and 1000 degrees of polymerization was suitable for training. We installed the eye model on an ocular surgery simulator, which allowed for the performance of a sequence of operations similar to ILM peeling. In conclusion, we developed a novel ocular surgery simulator for ILM peeling. The artificial ILM was peeled underwater in the same manner as in an actual operation.
Biosynthesis of glycosaminoglycans: associated disorders and biochemical tests.
Sasarman, Florin; Maftei, Catalina; Campeau, Philippe M; Brunel-Guitton, Catherine; Mitchell, Grant A; Allard, Pierre
2016-03-01
Glycosaminoglycans (GAG) are long, unbranched heteropolymers with repeating disaccharide units that make up the carbohydrate moiety of proteoglycans. Six distinct classes of GAGs are recognized. Their synthesis follows one of three biosynthetic pathways, depending on the type of oligosaccharide linker they contain. Chondroitin sulfate, dermatan sulfate, heparan sulfate, and heparin sulfate contain a common tetrasaccharide linker that is O-linked to specific serine residues in core proteins. Keratan sulfate can contain three different linkers, either N-linked to asparagine or O-linked to serine/threonine residues in core proteins. Finally, hyaluronic acid does not contain a linker and is not covalently attached to a core protein. Most inborn errors of GAG biosynthesis are reported in small numbers of patients. To date, in 20 diseases, convincing evidence for pathogenicity has been presented for mutations in a total of 16 genes encoding glycosyltransferases, sulfotransferases, epimerases or transporters. GAG synthesis defects should be suspected in patients with a combination of characteristic clinical features in more than one connective tissue compartment: bone and cartilage (short long bones with or without scoliosis), ligaments (joint laxity/dislocations), and subepithelial (skin, sclerae). Some produce distinct clinical syndromes. The commonest laboratory tests used for this group of diseases are analysis of GAGs, enzyme assays, and molecular testing. In principle, GAG analysis has potential as a general first-line diagnostic test for GAG biosynthesis disorders.
Wireless enzyme sensor system for real-time monitoring of blood glucose levels in fish.
Endo, Hideaki; Yonemori, Yuki; Hibi, Kyoko; Ren, Huifeng; Hayashi, Tetsuhito; Tsugawa, Wakako; Sode, Koji
2009-01-01
Periodic checks of fish health and the rapid detection of abnormalities are thus necessary at fish farms. Several studies indicate that blood glucose levels closely correlate to stress levels in fish and represent the state of respiratory or nutritional disturbance. We prepared a wireless enzyme sensor system to determine blood glucose levels in fish. It can be rapidly and conveniently monitored using the newly developed needle-type enzyme sensor, consisting of a Pt-Ir wire, Ag/AgCl paste, and glucose oxidase. To prevent the effects of interfering anionic species, such as uric acid and ascorbic acid, on the sensor response, the Pt-Ir electrode was coated with Nafion, and then glucose oxidase was immobilized on the coated electrode. The calibration curve of the glucose concentration was linear, from 0.18 to 144mg/dl, and the detection limit was 0.18mg/dl. The sensor was used to wirelessly monitor fish glucose levels. The sensor-calibrated glucose levels and actual blood glucose levels were in excellent agreement. The fluid of the inner sclera of the fish eyeball (EISF) was a suitable site for sensor implantation to obtain glucose sample. There was a close correlation between glucose concentrations in the EISF and those in the blood. Glucose concentrations in fish blood could be monitored in free-swimming fish in an aquarium for 3 days.
Automatic tissue segmentation of head and neck MR images for hyperthermia treatment planning
NASA Astrophysics Data System (ADS)
Fortunati, Valerio; Verhaart, René F.; Niessen, Wiro J.; Veenland, Jifke F.; Paulides, Margarethus M.; van Walsum, Theo
2015-08-01
A hyperthermia treatment requires accurate, patient-specific treatment planning. This planning is based on 3D anatomical models which are generally derived from computed tomography. Because of its superior soft tissue contrast, magnetic resonance imaging (MRI) information can be introduced to improve the quality of these 3D patient models and therefore the treatment planning itself. Thus, we present here an automatic atlas-based segmentation algorithm for MR images of the head and neck. Our method combines multiatlas local weighting fusion with intensity modelling. The accuracy of the method was evaluated using a leave-one-out cross validation experiment over a set of 11 patients for which manual delineation were available. The accuracy of the proposed method was high both in terms of the Dice similarity coefficient (DSC) and the 95th percentile Hausdorff surface distance (HSD) with median DSC higher than 0.8 for all tissues except sclera. For all tissues, except the spine tissues, the accuracy was approaching the interobserver agreement/variability both in terms of DSC and HSD. The positive effect of adding the intensity modelling to the multiatlas fusion decreased when a more accurate atlas fusion method was used. Using the proposed approach we improved the performance of the approach previously presented for H&N hyperthermia treatment planning, making the method suitable for clinical application.
Three-dimensional high-resolution ultrasonic imaging of the eye
NASA Astrophysics Data System (ADS)
Silverman, Ronald H.; Lizzi, Frederick L.; Kalisz, Andrew; Coleman, D. J.
2000-04-01
Very high frequency (50 MHz) ultrasound provides spatial resolution on the order of 30 microns axially by 60 microns laterally. Our aim was to reconstruct the three-dimensional anatomy of the eye in the full detail permitted by this fine- scale transducer resolution. We scanned the eyes of human subjects and anesthetized rabbits in a sequence of parallel planes 50 microns apart. Within each scan plane, vectors were also spaced 50 microns apart. Radio-frequency data were digitized at a rate of 250 MHz or higher. A series of spectrum analysis and segmentation algorithms was applied to data acquired in each plane; the outputs of these procedures were used to produce color-coded 3-D representations of the sclera, iris and ciliary processes to enhance 3-D volume rendered presentation. We visualized the radial pattern of individual ciliary processes in humans and rabbits and the geodetic web of supporting connections between the ciliary processes and iris that exist only in the rabbit. By acquiring data such that adjacent vectors and planes are separated by less than the transducer's lateral resolution, we were able to visualize structures, such as the ciliary web, that had not been seen before in-vivo. Our techniques offer the possibility of high- precision imaging and measurement of anterior segment structures. This would be relevant in monitoring of glaucoma, tumors, foreign bodies and other clinical conditions.
Expression of classical components of the renin-angiotensin system in the human eye.
White, Andrew J R; Cheruvu, Sarat C; Sarris, Maria; Liyanage, Surabhi S; Lumbers, Eugenie; Chui, Jeanie; Wakefield, Denis; McCluskey, Peter J
2015-03-01
The purpose of this study was to determine the relative expression of clinically-relevant components of the renin-angiotensin system (RAS) in the adult human eye. We obtained 14 post-mortem enucleated human eyes from patients whom had no history of inflammatory ocular disease nor pre-mortem ocular infection. We determined the gene expression for prorenin, renin, prorenin receptor, angiotensin-converting enzyme, angiotensinogen and angiotensin II Type 1 receptor, on tissue sections and in cultured human primary retinal pigment epithelial and iris pigment epithelial (RPE/IPE) cell lines, using both qualitative and quantitative reverse transcription polymerase chain reaction (RT-PCR). Protein expression was studied using indirect immunofluorescence (IF). Almost all components of the classical RAS were found at high levels, at both the transcript and protein level, in the eyes' uvea and retina; and at lower levels in the cornea, conjunctiva and sclera. There was a much lower level of expression in the reference cultured RPE/IPE cells lines. This study describes the distribution of RAS in the normal adult human eye and demonstrates the existence of an independent ocular RAS, with uveal and retinal tissues showing the highest expression of RAS components. These preliminary findings provide scope for examination of additional components of this system in the human eye, as well as possible differential expression under pathological conditions. © The Author(s) 2014.
He, Li; Frost, Michael R; Siegwart, John T; Norton, Thomas T
2018-03-01
Hyperopic refractive error is detected by retinal neurons, which generate GO signals through a direct emmetropization signaling cascade: retinal pigment epithelium (RPE) into choroid and then into sclera, thereby increasing axial elongation. To examine signaling early in this cascade, we measured gene expression in the retina and RPE after short exposure to hyperopia produced by minus-lens wear. Gene expression in each tissue was compared with gene expression in combined retina + RPE. Starting 24 days after normal eye opening, three groups of juvenile tree shrews (n = 7 each) wore a monocular -5 D lens. The untreated fellow eye served as a control. The "6h" group wore the lens for 6 h; the "24h" group wore the lens for 24 h; each group provided separate retina and RPE tissues. Group "24hC" wore the lens for 24 h and provided combined retina + RPE tissue. Quantitative PCR was used to measure the relative differences (treated eye vs. control eye) in mRNA levels for 66 candidate genes. In the retina after 6 h, mRNA levels for seven genes were significantly regulated: EGR1 and FOS (early intermediate genes) were down-regulated in the treated eyes. Genes with secreted protein products, BMP2 and CTGF, were down-regulated, whilst FGF10, IL18, and SST were up-regulated. After 24 h the pattern changed; only one of the seven genes still showed differential expression; BMP2 was still down-regulated. Two new genes with secreted protein products, IGF2 and VIP, were up-regulated. In the RPE, consistent with its role in receiving, processing, and transmitting GO signaling, differential expression was found for genes whose protein products are at the cell surface, intracellular, in the nucleus, and are secreted. After 6 h, mRNA levels for 17 genes were down-regulated in the treated eyes, whilst four genes (GJA1, IGF2R, LRP2, and IL18) were up-regulated. After 24 h the pattern was similar; mRNA levels for 14 of the same genes were still down-regulated; only LRP2 remained up-regulated. mRNA levels for six genes no longer showed differential expression, whilst nine genes, not differentially expressed at 6 h, now showed differential expression. In the combined retina + RPE after 24 h, mRNA levels for only seven genes were differentially regulated despite the differential expression of many genes in the RPE. Four genes showed the same expression in combined tissue as in retina alone, including up-regulation of VIP despite significant VIP down-regulation in RPE. Thus, hyperopia-induced GO signaling, as measured by differential gene expression, differs in the retina and the RPE. Retinal gene expression changed between 6 h and 24 h of treatment, suggesting evolution of the retinal response. Gene expression in the RPE was similar at both time points, suggesting sustained signaling. The combined retina + RPE does not accurately represent gene expression in either retina or, especially, RPE. When gene expression signatures were compared with those in choroid and sclera, GO signaling, as encoded by differential gene expression, differs in each compartment of the direct emmetropization signaling cascade. Copyright © 2018 Elsevier Ltd. All rights reserved.
Verification of Embolic Channel Causing Blindness Following Filler Injection.
Tansatit, Tanvaa; Moon, Hyoung Jin; Apinuntrum, Prawit; Phetudom, Thavorn
2015-02-01
Ocular complications following cosmetic filler injections are serious situations. This study provided scientific evidence that filler in the facial and the superficial temporal arteries could enter into the orbits and the globes on both sides. We demonstrated the existence of an embolic channel connecting the arterial system of the face to the ophthalmic artery. After the removal of the ocular contents from both eyes, liquid dye was injected into the cannulated channel of the superficial temporal artery in six soft embalmed cadavers and different color dye was injected into the facial artery on both sides successively. The interior sclera was monitored for dye oozing from retrograde ophthalmic perfusion. Among all 12 globes, dye injections from the 12 superficial temporal arteries entered ipsilateral globes in three and the contralateral globe in two arteries. Dye from the facial artery was infused into five ipsilateral globes and in three contralateral globes. Dye injections of two facial arteries in the same cadaver resulted in bilateral globe staining but those of the superficial temporal arteries did not. Direct communications between the same and different arteries of the four cannulated arteries were evidenced by dye dripping from the cannulating needle hubs in 14 of 24 injected arteries. Compression of the orbital rim at the superior nasal corner retarded ocular infusion in 11 of 14 arterial injections. Under some specific conditions favoring embolism, persistent interarterial anastomoses between the face and the eye allowed filler emboli to flow into the globe causing ocular complications.
[Osteogenesis imperfecta. Clinical, functional and multidisciplinary evaluation of 65 patients].
Fano, V; Rodríguez Celin, M; Del Pino, M; Buceta, S; Obregón, M G; Primomo, C; García, H; Miscione, H; Lejarraga, H
2010-05-01
Osteogenesis Imperfecta (OI) is a genetic disease, in which the main clinical features are increased bone fragility, pathological fractures, blue sclera, dentinogenesis imperfecta and conductive or mixed hearing loss. Clinical variability is wide. Although there is no curative treatment, there are several therapeutic tools capable of improving the course of the condition and patient quality of life. Sixty-five children seen in a Paediatric Hospital during six months in 2007 were evaluated. Thirty-five were type I OI, and thirty were types III-IV. Median age was 7.8 years (range 1.9-19.2); mean length of follow up was 4.7 years. The majority of children attended regular school for their corresponding age. Mean height was -1.4 sDS and -5.64 sDS in types I and III-IV respectively. Nineteen percent of patients were overweight and 11% were obese. Mean age at first orthopaedic surgery inserting telescopic rods was 6.5 years. Scoliosis was present in 44.6% of patients and was directly related to severity. Bleck's motor scale showed that 93% of patients with mild forms and 29% of severe forms had a sustainable walking ability. A wheelchair was used by 25% of patients. Family inheritance was confirmed in 65% of cases. Integral care using a multidisciplinary approach is required due to the complexity and clinical variability of the condition. Copyright 2009 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.
VisualEyes: a modular software system for oculomotor experimentation.
Guo, Yi; Kim, Eun H; Kim, Eun; Alvarez, Tara; Alvarez, Tara L
2011-03-25
Eye movement studies have provided a strong foundation forming an understanding of how the brain acquires visual information in both the normal and dysfunctional brain.(1) However, development of a platform to stimulate and store eye movements can require substantial programming, time and costs. Many systems do not offer the flexibility to program numerous stimuli for a variety of experimental needs. However, the VisualEyes System has a flexible architecture, allowing the operator to choose any background and foreground stimulus, program one or two screens for tandem or opposing eye movements and stimulate the left and right eye independently. This system can significantly reduce the programming development time needed to conduct an oculomotor study. The VisualEyes System will be discussed in three parts: 1) the oculomotor recording device to acquire eye movement responses, 2) the VisualEyes software written in LabView, to generate an array of stimuli and store responses as text files and 3) offline data analysis. Eye movements can be recorded by several types of instrumentation such as: a limbus tracking system, a sclera search coil, or a video image system. Typical eye movement stimuli such as saccadic steps, vergent ramps and vergent steps with the corresponding responses will be shown. In this video report, we demonstrate the flexibility of a system to create numerous visual stimuli and record eye movements that can be utilized by basic scientists and clinicians to study healthy as well as clinical populations.
Frucht-Pery, Joseph; Raiskup, Frederic; Ilsar, Michael; Landau, David; Orucov, Faik; Solomon, Abraham
2006-06-01
To compare the clinical outcome of pterygium surgery combining intraoperative mitomycin C (MMC) with a free conjunctival autograft, with three other methods of pterygium surgery, including intraoperative MMC alone, conjunctival autograft alone, and bare sclera without adjunctive treatment. Interventional, randomized and in part nonrandomized, prospective, comparative study. setting: A university medical center department of ophthalmology. One hundred and twenty patients underwent pterygium excision surgery. These patients were divided into four treatment groups. In group 1 (30 patients), MMC, 0.2 mg/ml, was applied for three minutes. In group 2 (30 patients), conjunctival autografting was performed. Group 3 (30 patients) received sodium chloride 0.9% only, and group 4 (30 patients) underwent conjunctival autografting combined with one minute application of MMC, 0.2 mg/ml. Recurrence rates and complications. Pterygium recurred in two patients (6.6%) in group 1, in four patients (13.3%) in group 2, in 14 patients (46.6%) in group 3, and in none of the patients in group 4. chi(2) analysis revealed a significantly lower recurrence rate in group 4 compared with group 2 (P = .038) and with group 3 (P < .0001). Epithelialization of the wounds was complete within 14 days of surgery. No complications were demonstrated in any of the study groups except for one case of minor melting of the flap in group 4. This study indicates that pterygium excision with a free conjunctival autograft combined with intraoperative low-dose MMC is a safe and effective technique in pterygium surgery.
Walsh, J E; Bergmanson, J P; Wallace, D; Saldana, G; Dempsey, H; McEvoy, H; Collum, L M
2001-09-01
Certain degenerative eye conditions occur predominantly nasally, at the limbal region, and are associated with solar ultraviolet radiation (UVR) induced damage. The relative contribution to the in vivo ocular flux of (a) the reflection of UVR incident on the skin of the nose onto the nasal limbus, and (b) the focusing of UVR incident on the temporal side of the cornea onto the nasal limbus were examined. A novel photodiode sensor array was used to measure the UVR field across the eye. In addition, a novel spectrometer set-up was used to measure the spectrum of radiation refracted across the cornea. The efficacy of UVR blocking hydrogel contact lenses in filtering incident UVR was assessed in vivo. Qualitative and quantitative data indicated an increase nasally of UVR. Photodiode readings showed a net UVR increase from the temporal to the nasal side. Transmission curves showed that most UVR incident on the limbal region is either absorbed by, or transmitted through, the ocular tissues. This radiation is filtered by UVR blocking soft contact lens. An increased UVR flux on the nasal side of the eye, due to reflection off the nasal skin, was identified in vivo. Any UVR passing through the cornea is either absorbed by the conjunctiva and/or transmitted through it onto the sclera where it is absorbed. UVR blocking hydrogel contact lenses can eliminate these sources of UVR.
Complement factor H: spatial and temporal expression and localization in the eye.
Mandal, Md Nawajes A; Ayyagari, Radha
2006-09-01
Complement factor H (CFH) is a component of the mammalian complement system, which regulates the alternative pathway of complement activation and protects the host cell from inappropriate complement activation. CFH is a key regulator of innate immunity, and CFH deficiency leads to membranoproliferative glomerulonephritis type II. A variation in human CFH, Y402H, has been shown to be associated with an increased risk for age-related macular degeneration. The authors describe studies on the spatial and temporal expression of the CFH gene and localization of this protein in ocular tissues to gain insight into its role in the eye. CFH expression in human and mouse tissues was studied by quantitative RT-PCR and Western blot analysis, and localization of CFH was studied by immunohistochemical analysis followed by fluorescence microscopy. In human and mouse, CFH expression was found to be similar to the highest level of expression in the liver. In ocular tissue, CFH was detected in the distalmost optic nerve (3 mm) cut from the scleral surface of the eyeball, sclera, RPE-choroid, retina, lens, and ciliary body. In mouse, Cfh expression was observed from early embryonic stages, and in the eye its expression increased with age. A significant level of CFH expression is maintained in different ocular tissues during development and aging. Sustained high levels of CFH expression in eye tissues suggest that this protein may play a role in protecting these tissues from indiscriminate complement activation and inflammatory insult.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Spotila, L.D.; Constantinou, C.D.; Sereda, L.
Mutations in the two genes for type I collagen (COL1A1 or COL1A2) cause osteogenesis imperfecta (OI), a heritable disease characterized by moderate to extreme brittleness of bone early in life. Here, the authors show that a 52-year-old post menopausal woman with severe osteopenia and a compression fracture of a thoracic vertebra had a mutation in the gene for the {alpha}2(I) chain of type I collagen (COL1A2) similar to mutations that cause OI. cDNA was prepared from the woman's skin fibroblast RNA and assayed for the presence of a mutation by treating DNA heteroduplexes with carbodiimide. The results indicated a sequencemore » variation in the region encoding amino acid residues 660-667 of the {alpha}2(I) chain. Further analysis demonstrated a single-base mutation that caused a serine-for-glycine substitution at position 661 of the {alpha}2(I) triple-helical domain. The substitution produced posttranslational overmodification of the collagen triple helix, as is seen with most glycine substitutions that cause OI. The patient had a history of five previous fractures, slightly blue sclerae, and slight hearing loss. Therefore, the results suggest that there may be phenotypic and genotypic overlap between mild osteogenesis imperfecta and postmenopausal osteoporosis, and that a subset of women with postmenopausal osteoporosis may have mutations in the genes for type I procollagen.« less
Tataru, CP; Pop, MD
2012-01-01
Rationale: Enucleation implants are covered with a material that allows the fixation of the extraocular rectus muscles. Usually, the implants are covered in donor sclera, which implies the risk of infection transmission, inflammation and implant rejection, being also an expensive procedure. The new materials used for implant meshing should be tested and a safer and cost effective solution should be researched. Objective: This study presents the results obtained after a 15-year use of an original prosthesis for the reconstruction of the orbital cavity after enucleation surgery. Methods and results: 42 eyes of 42 patients who underwent enucleation surgery for choroidal malignant melanoma were included in the study. The surgical technique was very similar to the classic enucleation, the major difference being the implant of a prosthesis made out of a Polymethyl methacrylate (PMMA) ball covered by a Polyethylene terephthalate (dacron) shell used in cardiovascular surgery. All the patients had a very good technical result, without the inflammation of the orbital cavity, conjunctiva or eyelids, which demonstrates a very high material tolerability and an excellent cosmetic result. Late implant expulsion appeared in 7.14% of the patients (3 cases). Discussion: The particularly good results obtained by using this technique, the absence of an inflammatory reaction after surgery, and the long lasting stability of the implant, recommend the method as being safe, with no major complications and a good esthetic result. AbbreviationsPolymethyl methacrylate (PMMA), Malignant choroidal melanoma (CMM) PMID:22802888
Chiang, B.; Kim, Y.C.; Doty, A.C.; Grossniklaus, H.E.; Schwendeman, S.P.; Prausnitz, M.R.
2016-01-01
Although effective drugs that lower intraocular pressure (IOP) in the management of glaucoma exist, their efficacy is limited by poor patient adherence to the prescribed eye drop regimen. To replace the need for eye drops, in this study we tested the hypothesis that IOP can be reduced for one month after a single targeted injection using a microneedle for administration of a glaucoma medication (i.e., brimonidine) formulated for sustained release in the supraciliary space of the eye adjacent to the drug’s site of action at the ciliary body. To test this hypothesis, brimonidine-loaded microspheres were formulated using poly(lactic acid) (PLA) to release brimonidine at a constant rate for 35 days and microneedles were designed to penetrate through the sclera, without penetrating into the choroid/retina, in order to target injection into the supraciliary space. A single administration of these microspheres using a hollow microneedle was performed in the eye of New Zealand White rabbits and was found to reduce IOP initially by 6 mm Hg and then by progressively smaller amounts for more than one month. All administrations were well tolerated without significant adverse events, although histological examination showed a foreign-body reaction to the microspheres. This study demonstrates, for the first time, that the highly-targeted delivery of brimonidine-loaded microspheres into the supraciliary space using a microneedle is able to reduce IOP for one month as an alternative to daily eye drops. PMID:26930266
Navarro, Rafael; Palos, Fernando; Lanchares, Elena; Calvo, Begoña; Cristóbal, José A
2009-01-01
To develop a realistic model of the optomechanical behavior of the cornea after curved relaxing incisions to simulate the induced astigmatic change and predict the optical aberrations produced by the incisions. ICMA Consejo Superior de Investigaciones Científicas and Universidad de Zaragoza, Zaragoza, Spain. A 3-dimensional finite element model of the anterior hemisphere of the ocular surface was used. The corneal tissue was modeled as a quasi-incompressible, anisotropic hyperelastic constitutive behavior strongly dependent on the physiological collagen fibril distribution. Similar behaviors were assigned to the limbus and sclera. With this model, some corneal incisions were computer simulated after the Lindstrom nomogram. The resulting geometry of the biomechanical simulation was analyzed in the optical zone, and finite ray tracing was performed to compute refractive power and higher-order aberrations (HOAs). The finite-element simulation provided new geometry of the corneal surfaces, from which elevation topographies were obtained. The surgically induced astigmatism (SIA) of the simulated incisions according to the Lindstrom nomogram was computed by finite ray tracing. However, paraxial computations would yield slightly different results (undercorrection of astigmatism). In addition, arcuate incisions would induce significant amounts of HOAs. Finite-element models, together with finite ray-tracing computations, yielded realistic simulations of the biomechanical and optical changes induced by relaxing incisions. The model reproduced the SIA indicated by the Lindstrom nomogram for the simulated incisions and predicted a significant increase in optical aberrations induced by arcuate keratotomy.
Dysli, Chantal; Enzmann, Volker; Sznitman, Raphael; Zinkernagel, Martin S.
2015-01-01
Purpose Quantification of retinal layers using automated segmentation of optical coherence tomography (OCT) images allows for longitudinal studies of retinal and neurological disorders in mice. The purpose of this study was to compare the performance of automated retinal layer segmentation algorithms with data from manual segmentation in mice using the Spectralis OCT. Methods Spectral domain OCT images from 55 mice from three different mouse strains were analyzed in total. The OCT scans from 22 C57Bl/6, 22 BALBc, and 11 C3A.Cg-Pde6b+Prph2Rd2/J mice were automatically segmented using three commercially available automated retinal segmentation algorithms and compared to manual segmentation. Results Fully automated segmentation performed well in mice and showed coefficients of variation (CV) of below 5% for the total retinal volume. However, all three automated segmentation algorithms yielded much thicker total retinal thickness values compared to manual segmentation data (P < 0.0001) due to segmentation errors in the basement membrane. Conclusions Whereas the automated retinal segmentation algorithms performed well for the inner layers, the retinal pigmentation epithelium (RPE) was delineated within the sclera, leading to consistently thicker measurements of the photoreceptor layer and the total retina. Translational Relevance The introduction of spectral domain OCT allows for accurate imaging of the mouse retina. Exact quantification of retinal layer thicknesses in mice is important to study layers of interest under various pathological conditions. PMID:26336634
Marcus, Inna; Tung, Irene T; Dosunmu, Eniolami O; Thiamthat, Warakorn; Freedman, Sharon F
2013-12-01
To compare anterior segment findings identified in young children using digital photographic images from the Lytro light field camera to those observed clinically. This was a prospective study of children <9 years of age with an anterior segment abnormality. Clinically observed anterior segment examination findings for each child were recorded and several digital images of the anterior segment of each eye captured with the Lytro camera. The images were later reviewed by a masked examiner. Sensitivity of abnormal examination findings on Lytro imaging was calculated and compared to the clinical examination as the gold standard. A total of 157 eyes of 80 children (mean age, 4.4 years; range, 0.1-8.9) were included. Clinical examination revealed 206 anterior segment abnormalities altogether: lids/lashes (n = 21 eyes), conjunctiva/sclera (n = 28 eyes), cornea (n = 71 eyes), anterior chamber (n = 14 eyes), iris (n = 43 eyes), and lens (n = 29 eyes). Review of Lytro photographs of eyes with clinically diagnosed anterior segment abnormality correctly identified 133 of 206 (65%) of all abnormalities. Additionally, 185 abnormalities in 50 children were documented at examination under anesthesia. The Lytro camera was able to document most abnormal anterior segment findings in un-sedated young children. Its unique ability to allow focus change after image capture is a significant improvement on prior technology. Copyright © 2013 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.
Scagnelli, Alyssa M; Walton, Stuart A; Liu, Chin-Chi; Acierno, Mark J
2018-05-01
CASE DESCRIPTION A 9-year-old 8.3-kg (18.3-lb) neutered male Miniature Schnauzer was referred for diagnosis and treatment of a sudden onset of lethargy, anorexia, vomiting, and pallor. CLINICAL FINDINGS On physical examination, the dog was lethargic with pale mucous membranes and a capillary refill time ≥ 2 seconds. Skin and sclera were mildly icteric. Signs of pain were elicited during abdominal palpation, and an enlarged spleen was noted. Results of agglutination testing and cytologic findings were consistent with immune-mediated hemolytic anemia (IMHA). No contributing factors for development of IMHA were identified. TREATMENT AND OUTCOME Initial treatment included management with immunosuppressant medications. Three packed RBC transfusions were administered, but clinical signs continued to progress. Therefore, therapeutic plasma exchange (TPE) was performed 5 and 9 days after admission. Following each TPE procedure, the dog had an appreciable clinical improvement and decrease in RBC autoagglutination, and the Hct stabilized. Serum IgG and IgM concentrations were measured during and after both TPE procedures. Despite anticoagulative treatment, the dog developed a thrombus in the splenic vein, necessitating a splenectomy. CLINICAL RELEVANCE The decrease and rebound in serum IgG and IgM concentrations following TPE provided evidence that TPE may have the same immunomodulatory effects in dogs as have been proposed to occur in people. Further, findings suggested that TPE may be a useful alternative in dogs with refractory IMHA when traditional treatments fail.
Ocular anatomy of the black pacu (Colossoma macropomum): gross, histologic, and diagnostic imaging.
Gustavsen, Kate A; Paul-Murphy, Joanne R; Weber, Ernest Scott; Zwingenberger, Allison L; Dunker, Freeland H; Dubielzig, Richard R; Reilly, Christopher M; Murphy, Christopher J
2018-01-30
To describe the ocular anatomy of the black pacu (Colossoma macropomum), a freshwater teleost fish of the Amazon River basin, including an unusual choroid laden with adipose tissue. Three adult black pacu were anesthetized and examined clinically and with ocular ultrasonography, then euthanized. Three fish were euthanized and their heads imaged immediately postmortem using computed tomography. One fish was euthanized and its exenterated eyes imaged by high-resolution magnetic resonance imaging. The exenterated eyes of all seven fish were fixed in formalin; eyes from three fish were examined grossly and histologically. Additionally, archived histologic sections from two smaller black pacu specimens were examined. Findings were consistent among the ocular imaging modalities used. Intrinsic to the sclera were circumferential ossicles and scleral cartilage. The lens was spherical and protruded through the ovoid pupil with an aphakic space inferiorly when the accommodative mechanism was relaxed under anesthesia. Both a small falciform process and epiretinal vasculature were present in the posterior segment. The retina was cone-rich, and processes of the retinal pigment epithelium enveloped the photoreceptor outer segments. Remarkably, the choroid occupied one-third of the anteroposterior length of the globe; histology confirmed that the bulk of the choroid was composed of adipose tissue. The eye of the pacu overall is typical of teleosts but has the notable and consistent finding of a substantive store of choroidal fat of unknown function. © 2018 American College of Veterinary Ophthalmologists.
Ichien, K.; Yamamoto, T.; Kitazawa, Y.; Oguri, A.; Ando, H.; Kondo, Y.
1997-01-01
AIMS—To determine whether a new, reversible thermosetting gel enhances mitomycin C transfer to target ocular tissues in the rabbit eye. METHODS—A 0.1 ml solution of mitomycin C containing 0.22 µg, 2.9 µg, or 28 µg of the agent dissolved in a reversible thermosetting gel consisting of methylcellulose, citric acid, and polyethylene glycol was injected subconjunctivally in 30 New Zealand albino rabbits. Scleral and conjunctival tissues were excised at 0.5, 1, 2, 4, or 24 hours after the injection and mitomycin C concentrations in these tissues were determined by high performance liquid chromatography. The concentration over time was approximated to a single exponential curve, and initial mitomycin C concentrations, time constants, and half life values were determined. Finally, the areas under the curves (AUCs) between 0.5 and 24 hours were calculated. RESULTS—The mitomycin C concentrations in the target tissues were dose dependent and decreased rapidly over 24 hours. Both the initial mitomycin C concentrations as well as AUCs in these eyes treated with mitomycin C, dissolved in a reversible thermosetting gel, were higher than those in eyes treated similarly in a previous study in which the gel was not used. CONCLUSION—Applied subconjunctivally in the rabbit eye, mitomycin C dissolved in the reversible thermosetting gel enhanced transfer of the agent to the sclera and the conjunctiva. PMID:9135413
Investigation of an outbreak of besnoitiosis in donkeys in northeastern Pennsylvania.
Ness, SallyAnne L; Peters-Kennedy, Jeanine; Schares, Gereon; Dubey, Jitender P; Mittel, Linda D; Mohammed, Hussni O; Bowman, Dwight D; Felippe, M Julia B; Wade, Susan E; Shultz, Nicole; Divers, Thomas J
2012-06-01
To describe the clinical, endoscopic, and serologic features of an outbreak of besnoitiosis in 2 donkey operations in northeastern Pennsylvania and to report the outcome of attempted treatment of 1 naturally infected individual. Observational study. 29 donkeys (Equus asinus) in northeastern Pennsylvania. Donkeys were examined for lesions suggestive of besnoitiosis in an outbreak investigation. Information was collected regarding the history and signalment of animals on each premises. Rhinolaryngoscopy was performed to identify nasopharyngeal and laryngeal lesions. Serum samples were collected for immunofluorescent antibody testing and immunoblotting for Besnoitia spp. Skin biopsy samples were obtained from 8 animals with lesions suggestive of besnoitiosis for histologic examination. Quantitative real-time PCR assay for Besnoitia spp was performed on tissue samples from 5 animals. Besnoitiosis was confirmed in 6 of the 8 suspected cases. The most common lesion site was the nares, followed by the skin and sclera. Donkeys with clinical signs of disease had higher serum antibody titers and tested positive for a greater number of immunoblot bands than did donkeys without clinical signs of disease. All animals evaluated by PCR assay tested positive. Putative risk factors for disease included age and sex. Ponazuril was not effective at treating besnoitiosis in a naturally infected donkey. Knowledge of clinical and serologic features of besnoitiosis in donkeys will assist clinicians in the diagnosis and prevention of this disease in donkey populations. Besnoitiosis may be an emerging disease of donkeys in the United States.
Ding, Jin-Dong; Kelly, Una; Landowski, Michael; Toomey, Christopher B.; Groelle, Marybeth; Miller, Chelsey; Smith, Stephanie G.; Klingeborn, Mikael; Singhapricha, Terry; Jiang, Haixiang; Frank, Michael M.; Bowes Rickman, Catherine
2016-01-01
Complement factor H (CFH) is an important regulatory protein in the alternative pathway of the complement system, and CFH polymorphisms increase the genetic risk of age-related macular degeneration dramatically. These same human CFH variants have also been associated with dense deposit disease. To mechanistically study the function of CFH in the pathogenesis of these diseases, we created transgenic mouse lines using human CFH bacterial artificial chromosomes expressing full-length human CFH variants and crossed these to Cfh knockout (Cfh−/−) mice. Human CFH protein inhibited cleavage of mouse complement component 3 and factor B in plasma and in retinal pigment epithelium/choroid/sclera, establishing that human CFH regulates activation of the mouse alternative pathway. One of the mouse lines, which express relatively higher levels of CFH, demonstrated functional and structural protection of the retina owing to the Cfh deletion. Impaired visual function, detected as a deficit in the scotopic electroretinographic response, was improved in this transgenic mouse line compared with Cfh−/− mice, and transgenics had a thicker outer nuclear layer and less sub–retinal pigment epithelium deposit accumulation. In addition, expression of human CFH also completely protected the mice from developing kidney abnormalities associated with loss of CFH. These humanized CFH mice present a valuable model for study of the molecular mechanisms of age-related macular degeneration and dense deposit disease and for testing therapeutic targets. PMID:25447048
Tang, Rui; Ma, Longfei; Xiang, Canhong; Wang, Xuedong; Li, Ang; Liao, Hongen; Dong, Jiahong
2017-09-01
Patients who undergo hilar cholangiocarcinoma (HCAC) resection with concomitant hepatectomy have a high risk of postoperative morbidity and mortality due to surgical trauma to the hepatic and biliary vasculature. A 58-year-old Chinese man with yellowing skin and sclera, abdominal distension, pruritus, and anorexia for approximately 3 weeks. Magnetic resonance cholangiopancreatography and enhanced computed tomography (CT) scanning revealed a mass over the biliary tree at the porta hepatis, which diagnosed to be s a hilar cholangiocarcinoma. Three-dimensional (3D) images of the patient's hepatic and biliary structures were reconstructed preoperatively from CT data, and the 3D images were used for preoperative planning and augmented reality (AR)-assisted intraoperative navigation during open HCAC resection with hemihepatectomy. A 3D-printed model of the patient's biliary structures was also used intraoperatively as a visual reference. No serious postoperative complications occurred, and the patient was tumor-free at the 9-month follow-up examination based on CT results. AR-assisted preoperative planning and intraoperative navigation might be beneficial in other patients with HCAC patients to reduce postoperative complications and ensure disease-free survival. In our postoperative analysis, we also found that, when the3D images were superimposed 3D-printed model using a see-through integral video graphy display device, our senses of depth perception and motion parallax were improved, compared with that which we had experienced intraoperatively using the videobased AR display system.
Bader, Hannah L; Keene, Douglas R; Charvet, Benjamin; Veit, Guido; Driever, Wolfgang; Koch, Manuel; Ruggiero, Florence
2009-01-01
Connective tissues ensure the cohesion of the tissues of the body, but also form specialized structures such as tendon and bone. Collagen XII may enhance the stability of connective tissues by bridging collagen fibrils, but its function is still unclear. Here, we used the zebrafish model to visualize its expression pattern in the whole organism. The zebrafish col12a1 gene is homologous to the small isoform of the tetrapod col12a1 gene. In agreement with the biochemical data reported for the small isoform, the zebrafish collagen XII alpha1 chain was characterized as a collagenase sensitive band migrating at approximately 200 kDa. Using newly generated polyclonal antibodies and anti-sense probes, we performed a comprehensive analysis of its expression in developing zebrafish. Collagen XII exhibited a much broader expression pattern than previously thought: it was ubiquitously expressed in the connective tissue sheaths (fascia) that encase the tissues and organs of the body. For example, it was found in sclera, meninges, epimysia and horizontal and vertical myosepta. Collagen XII was also detected in head mesenchyme, pharyngeal arches and within the spinal cord, where it was first expressed within and then at the lateral borders of the floor plate and at the dorsal midline. Furthermore, double immunofluorescence staining with laminin and immunogold electron microscopy revealed that collagen XII is associated with basement membranes. These data suggest that collagen XII is implicated in tissue cohesion by stabilizing fascia and by linking fascia to basement membranes.
Andreotti, Agda Marobo; Goiato, Marcelo Coelho; Moreno, Amália; Nobrega, Adhara Smith; Pesqueira, Aldiéris Alves; dos Santos, Daniela Micheline
2014-01-01
The aim of this study was to assess the effect of adding nanoparticles to N1 acrylic resin intended for artificial sclera, in terms of the color stability, microhardness, and flexural strength of the resin. Three hundred samples of N1 acrylic resin were used: 100 samples for color stability and microhardness tests (each test was performed on the opposite side of each sample), and 200 samples for flexural strength testing (100 samples before and after 1,008 hours of accelerated aging). Samples for each test were separated into ten groups (n=10), ie, without nanoparticles (control group) or with nanoparticles of zinc oxide, titanium dioxide (TiO₂), and barium sulfate at weight concentrations of 1%, 2%, and 2.5% (nanoparticle groups). Data were subjected to statistical analysis with nested analysis of variance and Tukey's test (P<0.05 significance level). Among the nanoparticle groups, the TiO₂ groups showed better color stability at all concentrations. Microhardness values increased after artificial aging, except for the control and zinc oxide groups. After aging, the 1%-2% TiO₂ groups had significantly higher microhardness values compared with the other nanoparticle groups. Before aging, there was a significant difference in flexural strength between the control and nanoparticle groups. After aging, the control and TiO₂ groups, regardless of concentration, showed the lowest flexural strength values. Incorporation of nanoparticles directly influenced the acrylic resin properties, with TiO₂ being the most influential nanoparticle in terms of the evaluated properties.
MRI helps depict clinically undetectable risk factors in advanced stage retinoblastomas.
Galluzzi, Paolo; Hadjistilianou, Theodora; Cerase, Alfonso; Toti, Paolo; Leonini, Sara; Bracco, Sandra; de Francesco, Sonia; Galimberti, Daniela; Balducci, Donatella; Piu, Pietro; Monti, Lucia; Bellini, Matteo; Caini, Mauro; Rossi, Alessandro
2015-02-01
This study compared high-resolution MRI with histology in advanced stage retinoblastomas in which ophthalmoscopy and ultrasonography did not give an exhaustive depiction of the tumour and/or its extension. MRI of orbits and head in 28 retinoblastoma patients (28 eyes) treated with primary enucleation were evaluated. Iris neoangiogenesis, infiltrations of optic nerve, choroid, anterior segment and sclera suspected at MR and histology were compared. Abnormal anterior segment enhancement (AASE) was also correlated with histologically proven infiltrations. Brain images were also evaluated. Significant values were obtained for: prelaminar optic nerve (ON) sensitivity (0.88), positive predictive value (PPV) (0.75) and negative predictive value (NPV) (0.71); post-laminar ON sensitivity (0.50), specificity (0.83), PPV (0.50) and NPV (0.83); overall choroid sensitivity (0.82), and massive choroid NPV (0.69); scleral specificity (1), and NPV (1). AASE correlated with iris neoangiogenesis in 14 out of 19 eyes, and showed significant values for: overall ON PPV (0.65), prelaminar ON sensitivity (0.65), and PPV (0.61), post-laminar ON NPV (0.64); overall choroid sensitivity (0.77), PPV (0.59) and NPV (0.73); scleral NPV (0.83); anterior segment sensitivity (1), and NPV (1). Odds ratios (OR) and accuracy were significant in scleral and prelaminar optic nerve infiltration. Brain examination was unremarkable in all cases. High-resolution MRI may add important findings to clinical evaluation of advanced stage retinoblastomas. © The Author(s) 2015 Reprints and permissions:]br]sagepub.co.uk/journalsPermissions.nav.
Improved method of producing satisfactory sections of whole eyeball by routine histology.
Arko-Boham, Benjamin; Ahenkorah, John; Hottor, Bismarck Afedo; Dennis, Esther; Addai, Frederick Kwaku
2014-02-01
To overcome the loss of structural integrity when eyeball sections are prepared by wax embedding, we experimentally modified the routine histological procedure and report satisfactorily well-preserved antero-posterior sections of whole eyeballs for teaching/learning purposes. Presently histological sections of whole eyeballs are not readily available because substantial structural distortions attributable to variable consistency of tissue components (and their undesired differential shrinkage) result from routine processing. Notably, at the dehydration stage of processing, the soft, gel-like vitreous humor considerably shrinks relative to the tough fibrous sclera causing collapse of the ocular globe. Additionally, the combined effects of fixation, dehydration, and embedding at 60°C renders the eye lens too hard for microtome slicing at thicknesses suitable for light microscopy. We satisfactorily preserved intact antero-posterior sections of eyeballs via routine paraffin wax processing procedure entailing two main modifications; (i) careful needle aspiration of vitreous humor and replacement with molten wax prior to wax infiltration; (ii) softening of lens in trimmed wax block by placing a drop of concentrated liquid phenol on it for 3 h during microtomy. These variations of the routine histological method produced intact whole eyeball sections with retinal detachment as the only structural distortion. Intact sections of the eyeball obtained compares well with the laborious, expensive, and 8-week long celloidin method. Our method has wider potential usability than costly freeze drying method which requires special skills and equipment (cryotome) and does not produce whole eyeball sections. Copyright © 2013 Wiley Periodicals, Inc.
Ninomiya, Hiroyoshi
2017-05-01
To examine the ocular circulation in California sea lions (Zalophus californianus). Eyes were obtained postmortem from three sea lions that died while in captivity. Specimens from sea lions were investigated using scanning electron microscopy (SEM) of vascular corrosion casts. The thermal characteristics of live animal eyes were measured using an infrared imaging system. The major orbital artery of the sea lion was the ophthalmic artery. The artery was remarkably thick in diameter, showed a marked convolution and formed an ophthalmic rete around the optic nerve at the posterior pole of the eyeball. The long posterior ciliary artery terminates to form a prominent inner arterial circle at the pupillary margin. The iridial arteries originated from the arterial circle showing either a crimped or somewhat coiled course, extending toward the root of the iris and formed a root supplying a large amount of blood to the iris and ciliary bodies. The venules in the conjunctiva formed a well-developed venous plexus. The vortex veins showed a dilation and constriction at the site passing through the sclera. Thermographic examination revealed that the eye showed a higher degree of thermal emission than adjacent skin areas. These characteristics suggest that the ocular vasculature might play roles in thermoregulation as well as in hemodynamics by draining a large amount of blood so that the appropriate operating temperature for the eye can be maintained in a deep and cold aquatic environment. © 2016 American College of Veterinary Ophthalmologists.
Progress towards a high-resolution retinal prosthesis
NASA Astrophysics Data System (ADS)
Butterwick, Alex; Vankov, Alex; Huie, Phil; Vijayraghavan, Karthik; Loudin, Jim; Palanker, Daniel
2007-02-01
Electronic retinal prostheses represent a potentially effective approach for restoring some degree of sight in blind patients with retinal degeneration. Functional restoration of sight would require hundreds to thousands of electrodes effectively stimulating remaining neurons in the retina. We present a design of an optoelectronic retinal prosthetic system having 3mm diameter retinal implant with pixel sizes down to 25 micrometers, which allows for natural eye scanning for observing a large field of view, as well as spatial and temporal processing of the visual scene to optimize the patient experience. Information from a head mounted video camera is processed in a portable computer and delivered to the implanted photodiode array by projection from the LCD goggles using pulsed IR (810 nm) light. Each photodiode converts pulsed light (0.5 ms in duration) into electric current with efficiency of 0.3 A/W using common bi-phasic power line. Power is provided by the inductively-coupled RF link from the coil on the goggles into a miniature power supply implanted between the sclera and the conjuctiva, and connected to subretinal implant with a thin 2-wire trans-scleral cable. 3-dimensional structures in the subretinal prosthesis induce retinal migration and thus ensure close proximity between stimulating electrodes and the target retinal neurons. Subretinal implantations of the 3-dimentional pillar and chamber arrays in RCS rats with 2 and 6 week follow-up demonstrate achievement of intimate proximity between the stimulation cites and the inner nuclear layer. In some instances formation of a fibrotic seal has been observed.
High-resolution ultrasonic imaging of the posterior segment.
Coleman, D Jackson; Silverman, Ronald H; Chabi, Almira; Rondeau, Mark J; Shung, K Kirk; Cannata, Jon; Lincoff, Harvey
2004-07-01
Conventional ophthalmic ultrasonography is performed using 10-megahertz (MHz) transducers. Our aim was to explore the use of higher frequency ultrasound to provide improved resolution of the posterior pole. Prospective case series. One normal subject and 5 subjects with pathologies affecting the posterior coats, including nevii, small melanomas, and macular hole. We modeled the frequency-dependent attenuation of ultrasound across the eye to develop an understanding of the range of frequencies that might be practically applied for imaging of the posterior pole. We compared images of the posterior coats made at 10, 15, and 20 MHz, and 20-MHz ultrasound images of pathologies with 10-MHz ultrasound and optical coherence tomography (OCT). Ability to resolve normal and pathologic structures affecting posterior coats of the eye. Modeling showed that frequencies of 20 to 25 MHz might be used for posterior pole imaging. Twenty-megahertz images allowed differentiation of the retina, choroid, and sclera. In addition, at 20 MHz the retina showed banding patterns suggesting an internal structure comparable in many respects to that seen in OCT and histology. Images of ocular pathology provided much improved detail relative to 10-MHz images and deeper penetration than OCT. Twenty-megahertz ultrasound can be practically employed for imaging of the posterior pole of the eye, providing a 2-fold improvement in resolution relative to conventional 10-MHz instruments. Although not providing the resolution of OCT, ultrasound can be used in the presence of optical opacities and allows evaluation of deeper tissue structures.
Real-time visualization of ultrasound-guided retrobulbar blockade: an imaging study.
Luyet, C; Eichenberger, U; Moriggl, B; Remonda, L; Greif, R
2008-12-01
Retrobulbar anaesthesia allows eye surgery in awake patients. Severe complications of the blind techniques are reported. Ultrasound-guided needle introduction and direct visualization of the spread of local anaesthetic may improve quality and safety of retrobulbar anaesthesia. Therefore, we developed a new ultrasound-guided technique using human cadavers. In total, 20 blocks on both sides in 10 embalmed human cadavers were performed. Using a small curved array transducer and a long-axis approach, a 22 G short bevel needle was introduced under ultrasound guidance lateral and caudal of the eyeball until the needle tip was seen 2 mm away from the optic nerve. At this point, 2 ml of contrast dye as a substitute for local anaesthetic was injected. Immediately after the injection, the spread of the contrast dye was documented by means of CT scans performed in each cadaver. The CT scans showed the distribution of the contrast dye in the muscle cone and behind the posterior sclera in all but one case. No contrast dye was found inside the optic nerve or inside the eyeball. In one case, there could be an additional trace of contrast dye behind the orbita. Our new ultrasound-guided technique has the potential to improve safety and efficacy of the procedure by direct visualization of the needle placement and the distribution of the injected fluid. Furthermore, the precise injection near the optic nerve could lead to a reduction of the amount of the local anaesthetic needed with fewer related complications.
Treatment of Inherited Eye Defects by Systemic Hematopoietic Stem Cell Transplantation.
Rocca, Celine J; Kreymerman, Alexander; Ur, Sarah N; Frizzi, Katie E; Naphade, Swati; Lau, Athena; Tran, Tammy; Calcutt, Nigel A; Goldberg, Jeffrey L; Cherqui, Stephanie
2015-11-01
Cystinosis is caused by a deficiency in the lysosomal cystine transporter, cystinosin (CTNS gene), resulting in cystine crystal accumulation in tissues. In eyes, crystals accumulate in the cornea causing photophobia and eventually blindness. Hematopoietic stem progenitor cells (HSPCs) rescue the kidney in a mouse model of cystinosis. We investigated the potential for HSPC transplantation to treat corneal defects in cystinosis. We isolated HSPCs from transgenic DsRed mice and systemically transplanted irradiated Ctns-/- mice. A year posttransplantation, we investigated the fate and function of HSPCs by in vivo confocal and fluorescence microscopy (IVCM), quantitative RT-PCR (RT-qPCR), mass spectrometry, histology, and by measuring the IOP. To determine the mechanism by which HSPCs may rescue disease cells, we transplanted Ctns-/- mice with Ctns-/- DsRed HSPCs virally transduced to express functional CTNS-eGFP fusion protein. We found that a single systemic transplantation of wild-type HSPCs prevented ocular pathology in the Ctns-/- mice. Engraftment-derived HSPCs were detected within the cornea, and also in the sclera, ciliary body, retina, choroid, and lens. Transplantation of HSPC led to substantial decreases in corneal cystine crystals, restoration of normal corneal thickness, and lowered IOP in mice with high levels of donor-derived cell engraftment. Finally, we found that HSPC-derived progeny differentiated into macrophages, which displayed tunneling nanotubes capable of transferring cystinosin-bearing lysosomes to diseased cells. To our knowledge, this is the first demonstration that HSPCs can rescue hereditary corneal defects, and supports a new potential therapeutic strategy for treating ocular pathologies.
Optical imaging of the retina in response to the electrical stimulation
NASA Astrophysics Data System (ADS)
Fujikado, Takashi; Okawa, Yoshitaka; Miyoshi, Tomomitsu; Hirohara, Yoko; Mihashi, Toshifumi; Tano, Yasuo
2008-02-01
Purposes: To determine if reflectance changes of the retina can be detected following electrical stimulation to the retina using a newly developed optical-imaging fundus camera. Methods: Eyes of cats were examined after pupil dilation. Retina was stimulated either focally by a ball-type electrode (BE) placed on the fenestrated sclera or diffusely using a ring-type electrode (RE) placed on the corneoscleral limbus. Electrical stimulation by biphasic pulse trains was applied for 4 seconds. Fundus images with near-infrared (800-880 nm) light were obtained between 2 seconds before and 20 seconds after the electrical stimulation (ES). A two-dimensional map of the reflectance changes (RCs) was constructed. The effect of Tetrodotoxin (TTX) was also investigated on RCs by ES using RE. Results: RCs were observed around the retinal locus where the stimulating electrodes were positioned (BE) or in the retina of the posterior pole (RE), in which the latency was about 0.5 to 1.0 sec and the peak time about 2 to 5 sec after the onset of ES. The intensity of the RCs increased with the increase of the stimulus current in both cases. RCs were completely suppressed after the injection of TTX. Conclusions: The functional changes of the retina either by focal or diffuse electrical stimulation were successfully detected by optical imaging of the retina. The contribution of retinal ganglion cells on RCs by ES was confirmed by TTX experiment. This method may be applied to the objective evaluation of the artificial retina.
NASA Astrophysics Data System (ADS)
Miyazawa, Arata; Hong, Young-Joo; Makita, Shuichi; Kasaragod, Deepa K.; Miura, Masahiro; Yasuno, Yoshiaki
2017-02-01
Local statistics are widely utilized for quantification and image processing of OCT. For example, local mean is used to reduce speckle, local variation of polarization state (degree-of-polarization-uniformity (DOPU)) is used to visualize melanin. Conventionally, these statistics are calculated in a rectangle kernel whose size is uniform over the image. However, the fixed size and shape of the kernel result in a tradeoff between image sharpness and statistical accuracy. Superpixel is a cluster of pixels which is generated by grouping image pixels based on the spatial proximity and similarity of signal values. Superpixels have variant size and flexible shapes which preserve the tissue structure. Here we demonstrate a new superpixel method which is tailored for multifunctional Jones matrix OCT (JM-OCT). This new method forms the superpixels by clustering image pixels in a 6-dimensional (6-D) feature space (spatial two dimensions and four dimensions of optical features). All image pixels were clustered based on their spatial proximity and optical feature similarity. The optical features are scattering, OCT-A, birefringence and DOPU. The method is applied to retinal OCT. Generated superpixels preserve the tissue structures such as retinal layers, sclera, vessels, and retinal pigment epithelium. Hence, superpixel can be utilized as a local statistics kernel which would be more suitable than a uniform rectangle kernel. Superpixelized image also can be used for further image processing and analysis. Since it reduces the number of pixels to be analyzed, it reduce the computational cost of such image processing.
Huang, Danping; Xu, Binbin; Yang, Zhiyun; Xu, Bing; Lin, Xiaolei; Yang, Xiaonan; Zhao, Jing
2015-01-01
To evaluate, using MRI, the extent and pattern of fibrovascular ingrowth into Medpor implants after modified evisceration. Contrast T1-weighted images were performed in 21 patients within 1.5- to69-month intervals after modified evisceration with primary Medpor implantation. In 6 patients, the images were obtained separately following 1- and 5-minute delays after contrast administration. No grade I enhancement occurred in these series. Grade II was observed in 2 patients (9.09%), grade III in 8 patients (36.36%), grade IV in 9 patients (40.91%), and grade V in 3 patients (13.64%). Significant correlation existed between the grade of enhancement and the postevisceration interval (r = 0.483, p = 0.023 < 0.05). The images demonstrated an enhancement pattern that started at the unwrapped posterior pole and anterior location of rectus muscles with progressive centripetal vascularization toward the center of the implant. At the early stage of recovery, the fibrous connective tissue was thick in front of Medpor spheres. In the 5-minute delay images of 6 patients, 2 patients failed to exhibit further enhancement; 2 patients exhibited enlarged and homogeneous enhancement; and 2 patients revealed more intense enhancement patterns. The medical ethics committee of Zhongshan Ophthalmic Center approved the study. Fibrovascular ingrowth into Medpor implants was satisfactory after the modified evisceration and correlated with the duration of the implants. The double layers of sclera effectively prevented the implant extrusion and exposure. The authors recommend waiting at least 5 minutes before obtaining MR images after contrast administration.
NASA Astrophysics Data System (ADS)
Hong, Young-Joo; Chan, Aaron C.; Kasaragod, Deepa K.; Makita, Shuichi; Miura, Masahiro; Yasuno, Yoshiaki
2017-02-01
Glaucoma is a group of eye diseases which results in optic nerve damage and vision loss. Optical coherence tomography (OCT) has been widely used to investigate geometric risk factor of glaucoma. However, material properties of ONH are also important to understand intra-ocular pressure related stress. We developed Jones-matrix based multifunctional posterior eye OCT (JM-OCT), which uses 1-μm band swept-source with a 100-kHz A-line rate. It provides three different optical properties, attenuation coefficient (AC), local birefringence (LB), and optical coherence angiography (OCA). We investigated the utility those properties for the investigation of normal ONH cases. 3 mm x 3 mm area around ONH was scanned for each eye, and biometric parameters were measured in hospital. Statistical analyses were performed with the mean values of above parameters at the regions of prelamina, lamina cribrosa, peripapillary sclera, and peripapillary nerve fiber layer, and biometric parameters of age, axial eye length, refractive error, and intraocular pressure. In qualitative observation, the lamina cribrosa generally shows more hyper signals in AC, LB, and OCA than prelamina. In t-test, AC, LB, and OCA showed significant difference (p < 0.05) between prelamina and lamina cribrosa, while conventional OCT did not. In correlation test, axial eye length is positively correlated with LB and AC in lamina cribrosa. And these LB and AC are also negatively correlated with the refractive error. Age was found to be negatively correlated with OCA in lamina cribrosa.
Yamanari, Masahiro; Nagase, Satoko; Fukuda, Shinichi; Ishii, Kotaro; Tanaka, Ryosuke; Yasui, Takeshi; Oshika, Tetsuro; Miura, Masahiro; Yasuno, Yoshiaki
2014-05-01
The relationship between scleral birefringence and biometric parameters of human eyes in vivo is investigated. Scleral birefringence near the limbus of 21 healthy human eyes was measured using polarization-sensitive optical coherence tomography. Spherical equivalent refractive error, axial eye length, and intraocular pressure (IOP) were measured in all subjects. IOP and scleral birefringence of human eyes in vivo was found to have statistically significant correlations (r = -0.63, P = 0.002). The slope of linear regression was -2.4 × 10(-2) deg/μm/mmHg. Neither spherical equivalent refractive error nor axial eye length had significant correlations with scleral birefringence. To evaluate the direct influence of IOP to scleral birefringence, scleral birefringence of 16 ex vivo porcine eyes was measured under controlled IOP of 5-60 mmHg. In these ex vivo porcine eyes, the mean linear regression slope between controlled IOP and scleral birefringence was -9.9 × 10(-4) deg/μm/mmHg. In addition, porcine scleral collagen fibers were observed with second-harmonic-generation (SHG) microscopy. SHG images of porcine sclera, measured on the external surface at the superior side to the cornea, showed highly aligned collagen fibers parallel to the limbus. In conclusion, scleral birefringence of healthy human eyes was correlated with IOP, indicating that the ultrastructure of scleral collagen was correlated with IOP. It remains to show whether scleral collagen ultrastructure of human eyes is affected by IOP as a long-term effect.
Tanaka, Thais S; Demirci, Hakan
2016-04-01
Cryopreserved ultra-thick human amniotic membrane (AM) is used for glaucoma surgery. We evaluated the use of cryopreserved ultra-thick human AM for conjunctival surface reconstruction after excision of a conjunctival tumor. We retrospectively reviewed the medical records of 28 patients who underwent conjunctival surface reconstruction with cryopreserved ultra-thick human AM after excision of the tumor. The AM was secured to the surrounding conjunctiva and underlying sclera with interrupted 8-0 Vicryl sutures. Clinical data regarding demographics, diagnosis, size and location of conjunctival tumors, patient outcome, and complications were gathered. Of 28 patients, 6 (21.4%) had malignant melanoma, 4 (14.3%) had squamous cell carcinoma, 6 (21.4%) had conjunctival intraepithelial neoplasia, 1 (3.6%) had sebaceous carcinoma, 1 (3.6%) had mucoepidermoid carcinoma, 1 (3.6%) had conjunctival intraepithelial dysplasia, 5 (17.9%) had pterygium, 2 (7.1%) had compound nevus, 1 (3.6%) had a large epithelial inclusion cyst, and 1 (3.6%) patient had a granuloma. The mean area of graft size was 156 ± 120 mm2. Postoperatively, the graft was well tolerated with no failure, discomfort, or dehiscence. During the 17-month mean follow-up, symblepharon, which was clinically nonsignificant, developed in 3 (11%) patients and partial stem cell deficiency was noted in 5 (18%) patients. Cryopreserved ultra-thick human AM is a well-tolerated, effective graft material that is easy to handle. It is a viable alternative for conjunctival surface reconstruction after excision of a conjunctival tumor.
Melanocytic Ophthalmic Neoplasms of the Domestic Veterinary Species: A Review.
Wang, Annie L; Kern, Thomas
2015-12-01
Melanocytic neoplasms in veterinary species occur in various ophthalmic locations including the eyelid, conjunctiva, cornea, sclera, anterior and posterior uvea, and orbit. Histology usually provides the definitive diagnosis for melanocytic ocular neoplasias. The degree of tissue invasiveness and anaplastic cellular characteristics are more reliable indicators of biological behavior than is mitotic index in most ophthalmic melanocytic tumors. Melanocytic neoplasias of the eyelid are predominantly benign in canines and equines, though in felines, there is the potential for metastasis, especially if the conjunctiva is involved. Limbal melanocytic tumors are predominantly benign in all the studied species, though there is a bimodal occurrence with this tumor type in canines, where those that appear in dogs younger than 4 years tended toward active growth, whereas those that appear in dogs older than 8 years tended to progress more slowly, and may not require therapy. The most common location for melanocytic ocular neoplasias in both canines and felines is the anterior uvea. Feline diffuse iris melanoma in particular has a higher incidence of metastasis than does canine nodular anterior uveal melanocytoma. In contrast, posterior uveal melanocytic tumors are rare in both canine and feline species and are considered benign. Orbital melanoma is rare in both canine and feline species; however, it generally carries a grave prognosis owing to its malignant nature. Knowledge of the general biological behavior and its variability among locations within the eye and between species is essential in therapeutic planning. Copyright © 2016 Elsevier Inc. All rights reserved.
Dees, D Dustin; Maclaren, Nicole E; Teixeira, Leandro; Dubielzig, Richard R
2013-07-01
This case report describes concurrent ocular melanosis and limbal melanocytoma in a 6-year-old Golden Retriever dog. Three years prior, the pet was examined for progressive corneal pigmentation and started on topical Tacrolimus but was subsequently lost to followup. Current ophthalmic examination revealed a large pigmented limbal mass and severe corneal pigmentation of the left eye as well as a small focal raised pigmented mass of the right third eyelid. Due to extent and rapidity of tumor growth, the left eye was removed via transconjunctival enucleation and submitted for histopathologic examination. At the time of surgery, numerous orbital structures including intraorbital fat, extraocular muscles, and portions of the proximal nasolacrimal drainage apparatus contained multifocal areas of black pigmentation. These tissues were subsequently removed and submitted for microscopic analysis. The pigmented mass of the right third eyelid was also excised. Histopathology of the left eye and orbital contents revealed a limbal melanocytoma extending to the bulbar conjunctiva and orbital space forming a large, markedly necrotic mass. Diffuse, severe ocular melanosis, abnormal stromal pigmentation of the sclera and orbital tissues, and corneal stromal pigmentation were noted. The mass of the right third eyelid was confirmed to be a conjunctival melanocytoma. To the authors' knowledge, this is the first report of concurrent ocular melanosis and limbal melanocytoma with orbital infiltration. The peculiar multifocal distribution of melanocytes throughout ocular connective tissues may explain the development of multiple melanocytic lesions in this patient. © 2012 American College of Veterinary Ophthalmologists.
NASA Astrophysics Data System (ADS)
Fialová, Stanislava; Augustin, Marco; Plasenzotti, Roberto; Rauscher, Sabine; Gröger, Marion; Pircher, Michael; Hitzenberger, Christoph K.; Baumann, Bernhard
2015-07-01
Animal models play an important role for understanding the pathophysiology of glaucoma and age-related macular degeneration. With these models, longitudinal studies can be performed and therefore there is need for non-invasive evaluation of disease progress. For that purpose optical coherence tomography (OCT) can be used. Since tissues with different polarization properties are important in these diseases, polarization sensitive OCT (PS-OCT) could be a valuable tool in preclinical research. In this work a high resolution PS-OCT (HR-PS-OCT) system was used in-vivo for rodent retinal imaging. A super luminescent diode with a bandwidth of 100 nm was used as a light source that yielded an axial resolution of 5.1 μm in air (3.8 μm in tissue). The A-scan rate was 83 kHz, a whole 3D dataset was acquired in a few seconds (1536x1024x200 pixels in 3.5 s) which reduced motion artifacts. Rats (Sprague-Dawley, Long-Evans and Brown Norway) as well as mice (C57BL/6) were imaged. High resolution reflectivity images showed all retinal layers in all animals. From acquired data also phase retardation, fast axis orientation and degree of polarization uniformity (DOPU) images were calculated. On phase retardation images sclera was identified as birefringent and retinal pigment epithelium (RPE) and choroid as depolarizing tissues. Our results demonstrate the suitability of the system for high speed/resolution imaging in follow up studies on rodents.
Clinical predictors of high risk histopathology in retinoblastoma.
Kashyap, Seema; Meel, Rachna; Pushker, Neelam; Sen, Seema; Bakhshi, Sameer; Sreenivas, Vishnubhatla; Sethi, Sumita; Chawla, Bhavna; Ghose, Supriyo
2012-03-01
Previous studies show that clinical features at presentation, in retinoblastoma patients, like glaucoma and neovascularization of iris are associated with a higher incidence of high risk histopathology findings (HRF) in enucleated eyes. Herein, we analyze association between clinical features at time of enucleation and occurrence of HRF including invasion of anterior chamber, iris, ciliary body, choroid (massive), sclera, extrascleral tissue, optic nerve beyond lamina cribrosa, and optic nerve cut end, in a large series of eyes enucleated for retinoblastoma. We retrospectively studied demographic, clinical, and histopathology findings in all retinoblastoma patients who underwent primary enucleation at our center, over a 5 years duration. Statistical analysis was done to find any association between clinical features at presentation and the presence of HRF. Three hundred twenty-six eyes were studied. Median age of presentation was 2 years. Glaucoma was the most common clinical finding at presentation apart from leucocoria. Out of 326 enucleated eyes, 28 (8.6%) had extrascleral and/or optic nerve transection invasion. Among remaining 298 eyes, with completely resected tumor, 115 (38.6%) had massive choroidal invasion, 54 (17%) had retrolaminar optic nerve invasion, and 24 (7%), 29 (9%), and 23(7%) had anterior chamber, iris, and ciliary body invasion, respectively. Age more than 2 years, lag period more than 3 months, hyphema, pseudohypopyon, staphyloma, and orbital cellulitis were associated with occurrence of three or more HRF on univariate analysis. Clinical variables including older age, longer lag period, hyphema, pseudohypopyon, staphyloma, and orbital cellulitis were strongly associated with occurrence of HRF in this study. Copyright © 2011 Wiley Periodicals, Inc.
Automated detection of Schlemm's canal in spectral-domain optical coherence tomography
NASA Astrophysics Data System (ADS)
Tom, Manu; Ramakrishnan, Vignesh; van Oterendorp, Christian; Deserno, Thomas M.
2015-03-01
Recent advances in optical coherence tomography (OCT) technology allow in vivo imaging of the complex network of intra-scleral aqueous veins in the anterior segment of the eye. Pathological changes in this network, draining the aqueous humor from the eye, are considered to play a role in intraocular pressure elevation, which can lead to glaucoma, one of the major causes of blindness in the world. Through acquisition of OCT volume scans of the anterior eye segment, we aim at reconstructing the three dimensional network of aqueous veins in healthy and glaucomatous subjects. A novel algorithm for segmentation of the three-dimensional (3D) vessel system in human Schlemms canal is presented analyzing frames of spectral domain OCT (SD-OCT) of the eyes surface in either horizontal or vertical orientation. Distortions such as vertical stripes are caused by the superficial blood vessels in the conjunctiva and the episclera. They are removed in the discrete Fourier domain (DFT) masking particular frequencies. Feature-based rigid registration of these noise-filtered images is then performed using the scale invariant feature transform (SIFT). Segmentation of the vessels deep in the sclera originating at or in the vicinity of or having indirect connection to the Schlemm's canal is then performed with 3D region growing technique. The segmented vessels are visualized in 3D providing diagnostically relevant information to the physicians. A proof-of-concept study was performed on a healthy volunteer before and after a pharmaceutical narrowing of Schlemm's canal. A relative decreases 17% was measured based on manual ground truth and the image processing method.
POSTERIOR STAPHYLOMAS IN EYES WITH RETINITIS PIGMENTOSA WITHOUT HIGH MYOPIA.
Xu, Xian; Fang, Yuxin; Yokoi, Tae; Shinohara, Kosei; Hirakata, Akito; Iwata, Takeshi; Tsunoda, Kazushige; Jonas, Jost B; Ohno-Matsui, Kyoko
2018-04-26
To describe features of posterior staphylomas in nonhighly myopic eyes with retinitis pigmentosa (RP). The retrospective observational case series study included patients with RP and an axial length of <26.5 mm and searched for eyes with posterior staphylomas. All study participants underwent fundus photography and optical coherence tomography. The study identified 13 eyes of 7 patients with a narrow macular staphyloma. Mean age was 40.9 ± 17.9 years (range 9-62 years) and mean axial length was 24.90 ± 0.69 mm. The staphyloma edges corresponded to the margin between the retinal atrophic area in the fundus midperiphery and the relatively unaffected fundus center. On vertically orientated optical coherence tomography images, the staphyloma edges showed a slight inward protrusion of the sclera and a ring-like localized choroidal thinning with choroidal rethickening in direction toward the fovea and toward the periphery of the fundus. The upper and lower staphyloma edges did not differ in steepness. The thickness of the subfoveal choroid (138.6 m ± 50.1 µm) was thinner than the normal range after adjusting for age and axial length in all eyes. Two eyes with advanced RP in the macula showed a subfoveal choroidal thickness of 95 µm and 88 µm. Narrow macular staphylomas can occur in nonhighly myopic eyes with RP and, in contrast to staphylomas in highly myopic eyes, show a less marked thinning of the subfoveal choroid. The occurrence of posterior staphylomas in nonhighly myopic eyes with RP may provide hints to unravel the etiology of posterior staphyloma formation.
A novel space ocular syndrome is driving technology advances on and off the planet
NASA Astrophysics Data System (ADS)
Donoviel, Dorit B.; Zimmer, Cheryl N.; Clayton, Richard
2017-05-01
Astronauts are experiencing ophthalmological changes including optic disc edema, globe flattening, choroidal folds, and significant hyperopic shifts. In a handful of cases in which it was measured, intracranial pressure as measured by lumbar punctures was elevated post-flight. The severity of symptoms is highly variable and the underlying etiology is unknown, but a spaceflight associated cephalad-fluid shift is thought to play a role. NASA requires portable, non-invasive, clinically-validated approaches to assessing the ocular and the cerebral physiological, anatomical, and functional changes. Multispectral Imaging (MSI) that enables instruments installed on satellites in space to observe Earth was applied in an ophthalmic medical device that is clinically being used on Earth and now being evaluated for use on humans in space. The Annidis RHA™ (Ottawa, Canada) uses narrow band light emitting diodes (LEDs) to create discrete slices of anatomical structures of the posterior pole of the eye. The LEDs cover a frequency range from 520 to 940 nm, which allow for specific visualization of the different features of the posterior segment of the eye including retina, choroid and optic nerve head. Interestingly, infrared illumination at 940 nm reflects from the posterior sclera, retro-illuminating the choroidal vasculature without the need for invasive contrast agents. Abnormalities in retinal, choroidal or cerebral venous drainage and/or arterial flow may contribute to the microgravity ocular syndrome (MOS) in astronauts; hence this space technology may prove to be invaluable for diagnosing not only the health of our planet but also of the humans living on it and above it.
Tornow, Ralf P; Schrems, Wolfgang A; Bendschneider, Delia; Horn, Folkert K; Mayer, Markus; Mardin, Christian Y; Lämmer, Robert
2011-09-29
Scanning laser polarimetry (SLP) results can be affected by an atypical retardation pattern (ARP). One reason for an ARP is the birefringence of the sclera. The purpose of this study was to investigate the influence of the peripapillary choroidal thickness (pChTh) on the occurrence of ARP. One hundred ten healthy subjects were investigated with SLP and spectral domain OCT. pChTh was measured in B-scan images at 768 positions using semiautomatic software. Values were averaged to 32 sectors and the total peripapillary mean. Subjects were divided into four groups according to the typical scan score (TSS) provided by the GDxVCC: group 1 TSS, 100; group 2 TSS, 90-99; group 3 TSS, 80-89; group 4 TSS, <80. Mean pChTh (± SD) in 110 healthy subjects was 141 μm (±49 μm). There was a significant correlation between pChTh and TSS (r = 0.608; P < 0.001). In TSS groups 1 to 4, mean pChTh was 168 μm (±38 μm), 148 μm (± 48 μm), 119 μm (±35 μm), and 92 (±42 μm). Mean pChTh of TSS groups 3 and 4 was significantly lower than that of TSS group 1 (P < 0.001). Low values of TSS resulting from the appearance of ARP in SLP are associated with low peripapillary choroidal thickness. Reduced choroidal thickness may result in an increased amount of confounding light getting to the SLP light detectors.
Baleva, Marta P; Mihaylova, Snejina; Yankova, Petja; Atanasova, Iliana; Nikolova-Vlahova, Milena; Naumova, Elissaveta
2016-01-01
Selective IgA deficiency (IgAD) is the most prevalent type of primary immune deficiencies, but partial IgA deficiency is even more common. Addison's disease is a rare condition associated with primary adrenal insufficiency due to infection or autoimmune destruction of the adrenals. The association between IgA deficiency and Addison's disease is very rare. We observed a 22-year-old male patient with marked darkening of the skin, especially on the palms and areolae, jaundice on the skin and sclera, astheno-adynamia, hypotension (80/50 mm Hg), and pain in the right hypochondrium. The laboratory investigations revealed increased serum levels of total and indirect bilirubin, AST, ALT, GGT and LDH, negative HBsAg, anti-HBc IgM, anti-HCV and anti-HAV IgM, very low serum IgA levels (0.16 g/l) with normal IgG and IgM, negative ANA, ANCA, AMA, LKM-1, anti-GAD-60, anti-IA-2, anti-thyroglobulin antibodies, a mild increase in anti-TPO antibodies titer, a marked increase in IgG anti-tissue transglutaminase antibodies, with no typical changes in cellular immunity, negative T-SPOT-TB test, HLA - A*01; B*08; DRB1*03; DQB1*02, karyotype - 46, XY. We present a rare case of partial IgA deficiency with Addison's disease, hepatitis, thyroiditis and positive anti-tissue transglutaminase antibodies. IgAD and some autoimmune disorders share several predisposing HLA genes, thus explaining the increased prevalence of IgAD in certain patient groups.
Correlation between refraction level and retinal breaks in myopic eye.
Alimanović-Halilović, Emina
2008-11-01
In this study we analyzed 180 myopic eyes in order to determine the refraction that is "critical" for the occurrence of retinal breaks as a main cause of retinal detachment. Detachment of retina involves separation of the neurosensory retina from the pigmented epithelium with the severe impairment of vision. After the focused ophthalmological assessment, determination of objective refraction, indirect binocular ophthalmoscopy, we compared the diagnosed retinal breaks according to the shape with the refraction. All the examined eyes were divided into six groups according to the axis length. Mean age of our patients was between 48,43 and 51,60 years with SD ranging from 13,88 to 18,45. The age differences among the groups were not statistically significant. This study included 102 (56,7%) male and 78 (43,3%) female patients and no statistically significant differences between genders was found regarding the occurrence of retinal breaks compared to refraction. The most dominant ruptures were the round ones (28,2%), followed by oval (25%), the category of multiple small holes (19,2%), horseshoe shaped (15,3%), and finally holes with operculum. In cases with myopic refraction ranging between 3,50 and 7,49 dsph, the frequency of retinal breaks statistically significantly differs from all other analyzed refractions. Also, there is positive correlation between the above mentioned myopic refraction and the frequency of retinal breaks. In order to prevent retinal detachment in a myopic eye, we suggest further thorough examinations of the eye fundus in patients with the above mentioned myopia. Diagnosing retinal breaks involves the application of adequate therapy: laser photocoagulation, cryotherapy, sclera buckling and pneumatic retinopexy.
Lim, F P M; Loh, B K; Cheung, C M G; Lim, L S; Chan, C M; Wong, D W K
2014-09-01
To evaluate imaging findings of patients with focal choroidal excavation (FCE) in the macula using swept-source optical coherence tomography (SS-OCT) and correlate it clinically. Prospective observational case series. Eleven consecutive patients (12 eyes) with FCE were described. Data on demographics and clinical presentation were collected and imaging findings (including color photography, fundus autofluorescence imaging, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and SS-OCT) were analyzed. The primary diagnosis was epiretinal membrane (two eyes), choroidal neovascularization (one eye), polypoidal choroidal vasculopathy (three eyes), central serous chorioretinopathy (one eye), and dry age-related macular degeneration (two eyes). Eleven out of 12 of the lesions were conforming. One presented with a non-conforming lesion that progressed to a conforming lesion. One eye had multiFCE and two had two overlapping choroidal excavations. Using the SS-OCT, we found the choroid to be thinned out at the area of FCE but sclera remained normal. The choroidal tissue beneath the FCE was abnormal, with high internal reflectivity and poor visualization of choroidal vessels. There was loss of contour of the outer choroidal boundary that appeared to be pulled inward by this abnormal choroidal tissue. A suprachoroidal space was noted beneath this choroidal tissue and the choroidal-scleral interface was smooth. Repeat SS-OCT 6 months after presentation showed the area of excavation to be stable in size. FCE can be associated with epiretinal membrane, central serous chorioretinopathy, and age-related macular degeneration. The choroid was thinned out in the area of FCE.
Lim, F P M; Loh, B K; Cheung, C M G; Lim, L S; Chan, C M; Wong, D W K
2014-01-01
Purpose To evaluate imaging findings of patients with focal choroidal excavation (FCE) in the macula using swept-source optical coherence tomography (SS-OCT) and correlate it clinically. Methods Prospective observational case series. Eleven consecutive patients (12 eyes) with FCE were described. Data on demographics and clinical presentation were collected and imaging findings (including color photography, fundus autofluorescence imaging, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and SS-OCT) were analyzed. Results The primary diagnosis was epiretinal membrane (two eyes), choroidal neovascularization (one eye), polypoidal choroidal vasculopathy (three eyes), central serous chorioretinopathy (one eye), and dry age-related macular degeneration (two eyes). Eleven out of 12 of the lesions were conforming. One presented with a non-conforming lesion that progressed to a conforming lesion. One eye had multiFCE and two had two overlapping choroidal excavations. Using the SS-OCT, we found the choroid to be thinned out at the area of FCE but sclera remained normal. The choroidal tissue beneath the FCE was abnormal, with high internal reflectivity and poor visualization of choroidal vessels. There was loss of contour of the outer choroidal boundary that appeared to be pulled inward by this abnormal choroidal tissue. A suprachoroidal space was noted beneath this choroidal tissue and the choroidal–scleral interface was smooth. Repeat SS-OCT 6 months after presentation showed the area of excavation to be stable in size. Conclusion FCE can be associated with epiretinal membrane, central serous chorioretinopathy, and age-related macular degeneration. The choroid was thinned out in the area of FCE. PMID:24946847
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chen, Qiang; Niu, Sijie; Yuan, Songtao
Purpose: In clinical research, it is important to measure choroidal thickness when eyes are affected by various diseases. The main purpose is to automatically segment choroid for enhanced depth imaging optical coherence tomography (EDI-OCT) images with five B-scans averaging. Methods: The authors present an automated choroid segmentation method based on choroidal vasculature characteristics for EDI-OCT images with five B-scans averaging. By considering the large vascular of the Haller’s layer neighbor with the choroid-sclera junction (CSJ), the authors measured the intensity ascending distance and a maximum intensity image in the axial direction from a smoothed and normalized EDI-OCT image. Then, basedmore » on generated choroidal vessel image, the authors constructed the CSJ cost and constrain the CSJ search neighborhood. Finally, graph search with smooth constraints was utilized to obtain the CSJ boundary. Results: Experimental results with 49 images from 10 eyes in 8 normal persons and 270 images from 57 eyes in 44 patients with several stages of diabetic retinopathy and age-related macular degeneration demonstrate that the proposed method can accurately segment the choroid of EDI-OCT images with five B-scans averaging. The mean choroid thickness difference and overlap ratio between the authors’ proposed method and manual segmentation drawn by experts were −11.43 μm and 86.29%, respectively. Conclusions: Good performance was achieved for normal and pathologic eyes, which proves that the authors’ method is effective for the automated choroid segmentation of the EDI-OCT images with five B-scans averaging.« less
Huang, Xuetao; Liu, Shaogang; Yang, Yezhen; Duan, Yiqin; Lin, Ding
2017-11-01
Corticosteroids have been used for treatment of posterior segment eye diseases, but the delivery of drug to the posterior segments is still a problem to resolve. In our study, we explore the feasibility of Sub-tenon's Controllable Continuous Drug Delivery to ocular posterior segment. Controllable continuous sub-tenon drug delivery (CCSDD) system, intravenous injections (IV) and sub-conjunctival injections (SC) were used to deliver dexamethasone disodium phosphate (DEXP) in rabbits, the dexamethasone concentration was measured in the ocular posterior segment tissue by Shimadzu LC-MS 2010 system at different time points in 24 h after first dose injection. Levels of dexamethasone were significantly higher at 12, 24 h in CCSDD than two other approaches, and at 3, 6 h in CCSDD than IV in vitreous body (p < 0.01); at 6, 12, 24 h in CCSDD than two other approaches, and at 1, 3 h in CCSDD than IV in retinal/choroidal compound (p < 0.01); at 3, 6, 12, 24 h in CCSDD than two other approaches, and at 1 h in CCSDD than IV in sclera (p < 0.05). The AUC 0-24 in CCSDD group is higher than two other groups in all ocular posterior segment tissue. Our results demonstrated that dexamethasone concentration could be sustained moderately higher in the posterior segment by CCSDD than SC and IV, indicating that CCSDD might be a therapeutic alternative to treat a variety of intractable posterior segment diseases.
NASA Astrophysics Data System (ADS)
Brooks, Daniel R.; Wozniak, Kaitlin T.; Knox, Wayne; Ellis, Jonathan D.; Huxlin, Krystel R.
2018-02-01
Intra-Tissue Refractive Index Shaping (IRIS) uses a 405 nm femtosecond laser focused into the stromal region of the cornea to induce a local refractive index change through multiphoton absorption. This refractive index change can be tailored through scanning of the focal region and variations in laser power to create refractive structures, such as gradient index lenses for visual refractive correction. Previously, IRIS was used to create 2.5 mm wide, square, -1 D cylindrical refractive structures in living cats. In the present work, we first wrote 400 μm wide bars of refractive index change at varying powers in enucleated cat globes using a custom flexure-based scanning system. The cornea and surrounding sclera were then removed and mounted into a wet cell. The induced optical phase change was measured with a Mach- Zehnder Interferometer (MZI), and appeared as fringe displacement, whose magnitude was proportional to the refractive index change. The interferograms produced by the MZI were analyzed with a Fourier Transform based algorithm in order to extract the phase change. This provided a phase change versus laser power calibration, which was then used to design the scanning and laser power distribution required to create -1.5 D cylindrical Fresnel lenses in cat cornea covering an area 6 mm in diameter. This prescription was inscribed into the corneas of one eye each of two living cats, under surgical anesthesia. It was then verified in vivo by contrasting wavefront aberration measurements collected pre- IRIS with those obtained over six months post-IRIS using a Shack-Hartmann wavefront sensor.
More irregular eye shape in low myopia than in emmetropia.
Tabernero, Juan; Schaeffel, Frank
2009-09-01
To improve the description of the peripheral eye shape in myopia and emmetropia by using a new method for continuous measurement of the peripheral refractive state. A scanning photorefractor was designed to record refractive errors in the vertical pupil meridian across the horizontal visual field (up to +/-45 degrees ). The setup consists of a hot mirror that continuously projects the infrared light from a photoretinoscope under different angles of eccentricity into the eye. The movement of the mirror is controlled by using two stepping motors. Refraction in a group of 17 emmetropic subjects and 11 myopic subjects (mean, -4.3 D; SD, 1.7) was measured without spectacle correction. For the analysis of eye shape, the refractive error versus the eccentricity angles was fitted with different polynomials (from second to tenth order). The new setup presents some important advantages over previous techniques: The subject does not have to change gaze during the measurements, and a continuous profile is obtained rather than discrete points. There was a significant difference in the fitting errors between the subjects with myopia and those with emmetropia. Tenth-order polynomials were required in myopic subjects to achieve a quality of fit similar to that in emmetropic subjects fitted with only sixth-order polynomials. Apparently, the peripheral shape of the myopic eye is more "bumpy." A new setup is presented for obtaining continuous peripheral refraction profiles. It was found that the peripheral retinal shape is more irregular even in only moderately myopic eyes, perhaps because the sclera lost some rigidity even at the early stage of myopia.
Morphological study of the eye and adnexa in capuchin monkeys (Sapajus sp.)
Silva, Danielle Nascimento; Oriá, Arianne Pontes; Araujo, Nayone Lantyer; Martins-Filho, Emanoel; Muramoto, Caterina; Libório, Fernanda de Azevedo
2017-01-01
The objective of this study was to describe the anatomic and histologic features of the Sapajus sp. eye, comparing similarities and differences of humans and other species of non-human primates for biomedical research purposes. Computed tomography (CT) of adnexa, eye and orbit live animal, as well as formolized pieces of the same structures of Sapajus sp. for anatomical and histological study were also performed. The anatomical description of the eye and adnexa was performed using the techniques of topographic dissection and exenteration. Histological fragments were fixated in buffered formalin 10%, processed by the routine paraffin inclusion technique, stained with hematoxylin-eosin and special stains. CT scan evaluation showed no differences between the live animal and the formolized head on identification of visual apparatus structures. Anatomic and histologic evaluation revealed rounded orbit, absence of the supraorbital foramen and frontal notch, little exposure of the sclera, with slight pigmentation of the exposed area and marked pigmentation at the sclerocorneal junction. Masson's Trichrome revealed the Meibomian glands, the corneal epithelium and Bowman's membrane; in the choroid, melanocytes and Bruch's membrane were observed; and in the retina, cones and rods as well as, optic nerve, the lamina cribrosa of the nerve fibers bundles. Toluidine blue highlighted the membranes: Bowman, Descemet and the endothelium; in the choroid: melanocytes; and in the retina: nuclear layers and retinal pigment epithelium. In view of the observed results Sapajus sp. is an important experimental model for research in the ophthalmology field, which has been shown due to the high similarity of its anatomical and histological structures with the human species. PMID:29206882
The effect of paclitaxel on conjunctival wound healing: a pilot study.
Koz, Ozlem Gurbuz; Ozhuy, Serife; Tezel, Gaye Guler; Karaman, Nazmiye; Unlu, Nursen; Yarangumeli, Alper; Kural, Gulcan
2007-01-01
To compare the effects of mitomycin C (MMC) and paclitaxel entrapped within Carbopol 980 hydrogel (CH) on conjunctival wound healing. Twenty rabbits were randomized into 2 groups. In group 1, limbal-based conjunctival flaps were created in both eyes. In this stage, eyes were randomized for 4 different processes. In process 1, a dry cellulose sponge soaked with 0.2 mg/mL of MMC was applied to the scleral surface. A cellulose sponge soaked with balanced saline solution was applied in the same manner in process 2. In process 3, paclitaxel 1 mg/mL entrapped within CH was placed between the conjunctiva and sclera. In process 4, CH without paclitaxel was applied in the same manner. The conjunctiva was then sutured. All procedures were applied in the same manner in both eyes of animals in group 2. Eyes from group 1 were sampled at the seventh day, and the sampling was also carried out in group 2 on day 14. The inflammatory response and fibrosis were evaluated with light microscopy. Among 4 different processes, lower cell counts and fibrosis scores were found in eyes treated with MMC and paclitaxel compared with balanced saline solution and CH groups (P<0.05). There was no difference between eyes treated with MMC and paclitaxel in terms of these histopathologic parameters (P>0.05). Paclitaxel was shown to provide MMC-like antifibrotic effects during conjunctival wound healing, particularly when delivered with CH and might be a promising alternative as an adjunctive antimetabolite in glaucoma filtration surgery.
Walsh, J.; Bergmanson, J.; Wallace, D.; Saldana, G.; Dempsey, H.; McEvoy, H.; Collum, L.
2001-01-01
BACKGROUND/AIMS—Certain degenerative eye conditions occur predominantly nasally, at the limbal region, and are associated with solar ultraviolet radiation (UVR) induced damage. The relative contribution to the in vivo ocular flux of (a) the reflection of UVR incident on the skin of the nose onto the nasal limbus, and (b) the focusing of UVR incident on the temporal side of the cornea onto the nasal limbus were examined. METHODS—A novel photodiode sensor array was used to measure the UVR field across the eye. In addition, a novel spectrometer set-up was used to measure the spectrum of radiation refracted across the cornea. The efficacy of UVR blocking hydrogel contact lenses in filtering incident UVR was assessed in vivo. RESULTS—Qualitative and quantitative data indicated an increase nasally of UVR. Photodiode readings showed a net UVR increase from the temporal to the nasal side. Transmission curves showed that most UVR incident on the limbal region is either absorbed by, or transmitted through, the ocular tissues. This radiation is filtered by UVR blocking soft contact lens. CONCLUSIONS—An increased UVR flux on the nasal side of the eye, due to reflection off the nasal skin, was identified in vivo. Any UVR passing through the cornea is either absorbed by the conjunctiva and/or transmitted through it onto the sclera where it is absorbed. UVR blocking hydrogel contact lenses can eliminate these sources of UVR. PMID:11520761
Seibel, Ira; Riechardt, Aline I; Erb-Eigner, Katharina; Böker, Alexander; Cordini, Dino; Heufelder, Jens; Joussen, Antonia M
2018-04-12
This study was performed to show long-term outcomes concerning metastasis rates and local recurrence rates after primary proton beam therapy in uveal melanoma with posterior extraocular extension (EOE) with the main focus on optic nerve invasion. Retrospective case series METHODS: All patients treated with primary proton beam therapy for choroidal or ciliary body melanoma with posterior EOE between July 1998 and August 2010 were included. EOE was either detected upon sonography at primary examination or during the surgical application of tantalum clips onto the sclera. Ultrasound was performed in each patient before surgery, and if EOE was detected, a magnetic resonance imaging (MRI) scan was performed to confirm EOE. All patients with tumors exceeding 6 mm in thickness or abutting the optic disc received a 1.5 Tesla MRI scan after clip surgery. To asses EOE during follow-up, either ultrasound examinations or-if initially detected only by MRI-MRI scans were performed during follow-up. A total of 27 patients underwent primary proton beam therapy. The EOE was separated into 3 growth types: Optic nerve infiltration in 10 patients, vortex vein infiltration in 9 patients, and transscleral growth post-equatorially in 8 patients. No local recurrences were found during the overall median follow-up of 80 months (11-168 months). Metastasis rates correlated with AJCC stages but not EOE volume. This study shows that posterior EOE can safely be treated by proton beam therapy, even if the optic nerve is infiltrated. MRI enables safe detection of optic nerve invasion. Copyright © 2018 Elsevier Inc. All rights reserved.
Sendelbeck, L; Moore, D; Urquhart, J
1975-08-01
We compared the patterns of pilocarpine distribution in the rabbit eye during two regimens that were comparably efficacious in human clinical use: an administration of 2% pilocarpine nitrate eyedrops, every six hours, for four and eight days, and a continuous delivery of pilocarpine for as long as eight days, at 20 mug/hr, from a membrane-controlled delivery system in the inferior cul-de-sac. Pilocarpine labeled with radioactive carbon (14C) was used as a tracer. With administration of eyedrops, 14C levels in ocular tissues rose and fell within each six-hour interval between eyedrops, but with the delivery system, 14C levels remained constant over the two- to eight-day period. In each tissue, the 14C level within the first hour after the most recently administered eyedrop always exceeded the constant level maintained by the delivery system. Three to six hours after eyedrop administration, the 14C levels in cornea, iris, and sclera were approximately equal to those maintained by the delivery system. However, in lens, vitreous humor, and conjunctiva, the 14C levels were always two to five times higher with eyedrop administration than with the delivery system. Only aqueous humor showed a significantly lower 14C level with eyedrops than with the delivery system, occurring late in the interval between eyedrops. Compared to eyedrop administration, the membrane-controlled delivery system produced drug levels in ocular tissues that were constant rather than variable with time, and appreciably lower in tissues where the drug made no known contribution to the reduction of pressure.
Pharmacokinetic basis for nonadditivity of intraocular pressure lowering in timolol combinations.
Lee, V H; Luo, A M; Li, S Y; Podder, S K; Chang, J S; Ohdo, S; Grass, G M
1991-10-01
The authors determined whether the ocular absorption of topically applied timolol in the pigmented rabbit was affected significantly by coadministration with either pilocarpine or epinephrine in the same drop to explain the nonadditivity in intraocular pressure lowering (IOP) seen clinically. They instilled 25 microliters of 0.65% timolol maleate solution (equivalent to 0.5% timolol), both in the presence and absence of 2.6% pilocarpine nitrate or 1% epinephrine bitartrate, into pigmented rabbit eyes. The time course of timolol concentration in the conjunctiva, anterior sclera, corneal epithelium, corneal stroma, aqueous humor, iris-ciliary body, and lens was monitored for 360 min by using reversed-phase high-performance liquid chromatography. The area under the timolol concentration-time curve in all but one of the anterior segment tissues was reduced by 20-50% (mean, 40%) when timolol was coadministered with pilocarpine and by 20-70% (mean, 42%) when timolol was coadministered with epinephrine. Such an effect was not a result of alterations in corneal permeability or aqueous humor turnover rate, nor was it related to the extent of systemic absorption caused by pilocarpine and epinephrine. Rather, the reduction in ocular timolol absorption may have been caused by the accelerated washout of timolol by tears stimulated by the coadministered drugs and, to a lesser extent, by the loss of timolol through binding to the increased amount of tear proteins induced by the coadministered drugs. Thus, the nonadditivity in IOP lowering from timolol-pilocarpine and timolol-epinephrine combinations is probably caused by changes in precorneal timolol clearance.
Assessing the precision of gaze following using a stereoscopic 3D virtual reality setting.
Atabaki, Artin; Marciniak, Karolina; Dicke, Peter W; Thier, Peter
2015-07-01
Despite the ecological importance of gaze following, little is known about the underlying neuronal processes, which allow us to extract gaze direction from the geometric features of the eye and head of a conspecific. In order to understand the neuronal mechanisms underlying this ability, a careful description of the capacity and the limitations of gaze following at the behavioral level is needed. Previous studies of gaze following, which relied on naturalistic settings have the disadvantage of allowing only very limited control of potentially relevant visual features guiding gaze following, such as the contrast of iris and sclera, the shape of the eyelids and--in the case of photographs--they lack depth. Hence, in order to get full control of potentially relevant features we decided to study gaze following of human observers guided by the gaze of a human avatar seen stereoscopically. To this end we established a stereoscopic 3D virtual reality setup, in which we tested human subjects' abilities to detect at which target a human avatar was looking at. Following the gaze of the avatar showed all the features of the gaze following of a natural person, namely a substantial degree of precision associated with a consistent pattern of systematic deviations from the target. Poor stereo vision affected performance surprisingly little (only in certain experimental conditions). Only gaze following guided by targets at larger downward eccentricities exhibited a differential effect of the presence or absence of accompanying movements of the avatar's eyelids and eyebrows. Copyright © 2015 Elsevier Ltd. All rights reserved.
Shape Analysis of the Peripapillary RPE Layer in Papilledema and Ischemic Optic Neuropathy
Kupersmith, Mark J.; Rohlf, F. James
2011-01-01
Purpose. Geometric morphometrics (GM) was used to analyze the shape of the peripapillary retinal pigment epithelium–Bruch's membrane (RPE/BM) layer imaged on the SD-OCT 5-line raster in normal subjects and in patients with papilledema and ischemic optic neuropathy. Methods. Three groups of subjects were compared: 30 normals, 20 with anterior ischemic optic neuropathy (AION), and 25 with papilledema and intracranial hypertension. Twenty equidistant semilandmarks were digitized on OCT images of the RPE/BM layer spanning 2500 μm on each side of the neural canal opening (NCO). The data were analyzed using standard GM techniques, including a generalized least-squares Procrustes superimposition, principal component analysis, thin-plate spline (to visualize deformations), and permutation statistical analysis to evaluate differences in shape variables. Results. The RPE/BM layer in normals and AION have a characteristic V shape pointing away from the vitreous; the RPE/BM layer in papilledema has an inverted U shape, skewed nasally inward toward the vitreous. The differences were statistically significant. There was no significant difference in shapes between normals and AION. Pre- and posttreatment OCTs, in select cases of papilledema, showed that the inverted U-shaped RPE/BM moved posteriorly into a normal V shape as the papilledema resolved with weight loss or shunting. Conclusions. The shape difference in papilledema, absent in AION, cannot be explained by disc edema alone. The difference is a consequence of both the translaminar pressure gradient and the material properties of the peripapillary sclera. GM offers a novel way of statistically assessing shape differences of the peripapillary optic nerve head. PMID:21896851
Sclerocornea Associated With the Chromosome 22q11.2 Deletion Syndrome
Binenbaum, Gil; McDonald-McGinn, Donna M.; Zackai, Elaine H.; Walker, B. Michael; Coleman, Karlene; Mach, Amy M.; Adam, Margaret; Manning, Melanie; Alcorn, Deborah M.; Zabel, Carrie; Anderson, Dennis R.; Forbes, Brian J.
2009-01-01
Reported ocular findings in the 22q11.2 deletion syndrome (which encompasses the phenotypes of DiGeorge, velocardiofacial, and Takao (conotruncal-anomaly-face) syndromes) have included posterior embryotoxon (prominent, anteriorly displaced Schwalbe’s line at the corneal limbus or edge), retinal vascular tortuosity, eyelid hooding, strabismus, and astigmatism. We present seven 22q11.2 patients from multiple centers with sclerocornea, an eye finding previously unreported in the literature. Four boys and three girls were identified with sclerocornea, systemic DGS/VCFS findings, and fluorescence in situ hybridization (FISH)-confirmed microdeletion at chromosome 22q11.2. FISH diagnosis was perinatal in six patients but at 2 years of age in one child. Sclerocornea was bilateral in five patients. Findings included descemetocele (five eyes), microophthalmos (one eye), iridocorneal adhesions (one bilateral case), and severe anterior segment dysgenesis (one eye). Two patients underwent bilateral corneal transplantation; another two were scheduled for possible unilateral transplant. Sclerocornea is a static congenital condition in which the cornea is opaque and vascularized and resembles the sclera. The novel finding of sclerocornea suggests that a genetic locus at 22q11.2 may be involved in anterior segment embryogenesis. In most of our patients, the diagnostic process was underway, but in one patient 22q11.2 deletion was not suspected until after the child had already been undergoing treatment for sclerocornea for 2 years. Sclerocornea should be added to the clinical manifestations of the 22q11.2 deletion syndrome. Ophthalmologists diagnosing sclerocornea in children with systemic findings suggestive of 22q11.2 deletion should ensure appropriate genetic referral. PMID:18324686
Tang, Rui; Ma, Longfei; Xiang, Canhong; Wang, Xuedong; Li, Ang; Liao, Hongen; Dong, Jiahong
2017-01-01
Abstract Rationale: Patients who undergo hilar cholangiocarcinoma (HCAC) resection with concomitant hepatectomy have a high risk of postoperative morbidity and mortality due to surgical trauma to the hepatic and biliary vasculature. Patient concerns: A 58-year-old Chinese man with yellowing skin and sclera, abdominal distension, pruritus, and anorexia for approximately 3 weeks. Diagnoses: Magnetic resonance cholangiopancreatography and enhanced computed tomography (CT) scanning revealed a mass over the biliary tree at the porta hepatis, which diagnosed to be s a hilar cholangiocarcinoma. Intervention: Three-dimensional (3D) images of the patient's hepatic and biliary structures were reconstructed preoperatively from CT data, and the 3D images were used for preoperative planning and augmented reality (AR)-assisted intraoperative navigation during open HCAC resection with hemihepatectomy. A 3D-printed model of the patient's biliary structures was also used intraoperatively as a visual reference. Outcomes: No serious postoperative complications occurred, and the patient was tumor-free at the 9-month follow-up examination based on CT results. Lessons: AR-assisted preoperative planning and intraoperative navigation might be beneficial in other patients with HCAC patients to reduce postoperative complications and ensure disease-free survival. In our postoperative analysis, we also found that, when the3D images were superimposed 3D-printed model using a see-through integral video graphy display device, our senses of depth perception and motion parallax were improved, compared with that which we had experienced intraoperatively using the videobased AR display system. PMID:28906410
Gilger, Brian C; Wilkie, David A; Clode, Allison B; McMullen, Richard J; Utter, Mary E; Komaromy, Andras M; Brooks, Dennis E; Salmon, Jacklin H
2010-09-01
To determine the long-term efficacy, complications, and duration of effect of a cyclosporine (CsA) suprachoroidal implant (CSI) in horses with equine recurrent uveitis (ERU). Horses with ERU were treated with a 6-mm diameter, 25 mg, reservoir matrix CsA implant in the deep sclera adjacent to the suprachoroidal space. Horses with follow-up >1 year were examined for frequency of uveitis episodes, complications, and vision at last recheck. Data from 151 eyes of 133 horses from the USA and Europe that had CsA devices implanted for ERU were reviewed. Follow-up time ranged from 13 to 85 months after surgery, with a mean and median follow-up time of 28.9 and 26.3 months, respectively. Overall, at last follow-up 78.8% of eyes were considered visual and the overall mean frequency of uveitis episodes after CSI was 0.09 ± SD 0.08 episodes per month. The most common complications leading to vision loss at last follow-up were persistent uveitis episodes (54%), glaucoma (22%), mature cataracts (16%), and retinal detachment (6%). Persistent uveitis episodes tended to be the highest cause of vision loss in horses with <24 months and >48 months of follow-up. This study demonstrated the long-term maintenance of vision of horses with ERU implanted with a CSI. The increased vision loss related to uveitis episode of inflammation in eyes after the likely depletion of CsA from the CSI suggests that a repeat CSI may be required at or before 48 months after surgery.
Terada, Nobuo; Ohno, Nobuhiko; Saitoh, Sei; Fujii, Yasuhisa; Ohguro, Hiroshi; Ohno, Shinichi
2007-07-01
The wavelength of Raman-scattered light depends on the molecular composition of the substance. This is the first attempt to acquire Raman spectra of a mouse eyeball removed from a living mouse, in which the eyeball was preserved using the "in vivo cryotechnique" followed by freeze-drying. Eyeballs were cryofixed using a rapid freezing cryotechnique, and then sliced in the cryostat machine. The slices were sandwiched between glass slides, freeze-dried, and analyzed with confocal Raman microscopy. Important areas including various eyeball tissue layers were selected using bright-field microscopy, and then the Raman spectra were obtained at 240 locations. Four typical patterns of Raman spectra were electronically mapped on the specimen images obtained by the bright-field microscopy. Tissue organization was confirmed by embedding the same eyeball slice used for Raman spectra into epoxy resin and the thick sections were prepared with the inverted capsule method. Each Raman spectral pattern represents a different histological layer in the eyeball which was mapped by comparing the images of toluidine blue staining and Raman mapping with different colors. In the choroid and pigment cell layer, the Raman spectrum had two peaks, corresponding to melanin. Some of the peaks of the Raman spectra obtained from the blood vessels in sclera and the photoreceptor layer were similar to those obtained from the purified hemoglobin and rhodopsin proteins, respectively. Our experimental protocol can distinguish different tissue components with Raman microscopy; therefore, this method can be very useful for examining the distribution of a biological structures and/or chemical components in rapidly frozen freeze-dried tissue.
The clinical features of osteogenesis imperfecta in Vietnam.
Binh, Ho Duy; Maasalu, Katre; Dung, Vu Chi; Ngoc, Can T Bich; Hung, Ton That; Nam, Tran V; Nhan, Le N Thanh; Prans, Ele; Reimann, Ene; Zhytnik, Lidiia; Kõks, Sulev; Märtson, Aare
2017-01-01
Osteogenesis imperfecta (OI) has not been studied in a Vietnamese population before. The aim of this study was to systematically collect epidemiological information, investigate clinical features and create a clinical database of OI patients in Vietnam for future research and treatment strategy development. Participants underwent clinical and physical examinations; also medical records were reviewed. Genealogical information was collected and family members' phenotypical manifestations recorded. Cases were classified according to the Sillence classification. In total, 146 OI patients from 120 families were studied: 46 with OI Type I, 46 with Type III and 54 with Type IV. Almost patients had skeletal deformations. One hundred and forty-two had a history of fractures, 117 blue sclera, 89 dentinogenesis imperfecta and 26 hearing loss. The total number of fractures was 1,932. Thirty-four patients had intra-uterine fractures and nine had perinatal fractures. Surgery was performed 163 times in 58 patients; 100 osteosyntheses and 63 osteotomies. Bisphosphonate treatment was used in 37 patients. The number of affected individuals and predominance of severe forms of OI indicate that the disease is under diagnosed in Vietnam, especially in cases without a family history or with mild form of OI. Deformities appeared in all patients with different severity and localisation, affecting mostly the lower limbs. OI medical and surgical treatment rates are low and in most cases surgery was performed due to fractures. Compared to previous studies, our results indicate a lower OI prevalence and greater severity of symptoms in the Vietnamese population when compared with other areas. Further investigation, improved diagnosis and treatment are needed to increase the patients' quality of life.
Pepin, Melanie G; Byers, Peter H
2015-12-01
Non-accidental injury (NAI) is a major medical concern in the United States. One of the challenges in evaluation of children with unexplained fractures is that genetic forms of bone fragility are one of the differential diagnoses. Infants who present with fractures with mild forms of osteogenesis imperfecta (OI) (OI type I or OI type IV), the most common genetic form of bone disease leading to fractures might be missed if clinical evaluation alone is used to make the diagnosis. Diagnostic clinical features (blue sclera, dentinogenesis imperfecta, Wormian bones on X-rays or positive family history) may not be present or apparent at the age of evaluation. The evaluating clinician faces the decision about whether genetic testing is necessary in certain NAI cases. In this review, we outline clinical presentations of mild OI and review the history of genetic testing for OI in the NAI versus OI setting. We summarize our data of molecular testing in the Collagen Diagnostic Laboratory (CDL) from 2008 to 2014 where NAI was noted on the request for DNA sequencing of COL1A1 and COL1A2. We provide recommendations for molecular testing in the NAI versus OI setting. First, DNA sequencing of COL1A1, COL1A2, and IFITM5 simultaneously and duplication/deletion testing is recommended. If a causative variant is not identified, in the absence of a pathologic clinical phenotype, no additional gene testing is indicated. If a VUS is found, parental segregation studies are recommended. © 2015 Wiley Periodicals, Inc.
Yang, Mei; Yang, Yangfan; Lei, Ming; Ye, Chengtian; Zhao, Chunshun; Xu, Jiangang; Wu, Kaili; Yu, Minbin
2016-11-01
Pirfinedone (PFD) is a novel agent which has the potential to prevent scarring in the eyes. The 0.5% PFD eye drops exhibits poor bioavailability. Whereas, the feasibility of using contact lens as ocular drug delivery device initiated novel possibilities. To evaluate the delivery of PFD by soft contact lens (SCL) in vivo, we screened the most suitable lens material for PFD among various commercially available SCL materials in vitro. Firstly, 11 different SCLs (-1.00 diopter) were respectively soaked in 2 ml of 0.05% PFD-loading solution for 24 h to fully absorb drug, and then placed in fresh phosphate buffered saline (PBS) to release the drug. PFD concentration in PBS was determined by ultraviolet absorbance at 310 nm. Secondly, by immersing in 2 ml of 0.5% PFD eye drops for 24 h, the polymacon lens (0.00 diopter) was then placed on the cornea of New Zealand rabbits. PFD concentrations were detected by high performance liquid chromatography (HPLC) in tears, aqueous humor, conjunctiva, cornea, and sclera at different time points. PFD showed some affinity for pHEMA-based lenses and the polymacon lens more slowly released more amount of PFD than any other lens in vitro (p < 0.001). Compared with eye drops, drug-loaded SCLs greatly enhanced the retention time and concentrations of PFD in cornea and aqueous humor and consequently improved the bioavailability of PFD. Polymacon-based SCL is probably a promising vehicle to be an effective ophthalmic delivery system for PFD.
Oo, Myat Lin; Anrather, Josef; Schaeren-Wiemers, Nicole; Alonso, Miguel A.; Fischetti, Vincent A.; McClain, Mark S.; Vartanian, Timothy
2015-01-01
Clostridium perfringens ε-toxin (ETX) is a potent pore-forming toxin responsible for a central nervous system (CNS) disease in ruminant animals with characteristics of blood-brain barrier (BBB) dysfunction and white matter injury. ETX has been proposed as a potential causative agent for Multiple Sclerosis (MS), a human disease that begins with BBB breakdown and injury to myelin forming cells of the CNS. The receptor for ETX is unknown. Here we show that both binding of ETX to mammalian cells and cytotoxicity requires the tetraspan proteolipid Myelin and Lymphocyte protein (MAL). While native Chinese Hamster Ovary (CHO) cells are resistant to ETX, exogenous expression of MAL in CHO cells confers both ETX binding and susceptibility to ETX-mediated cell death. Cells expressing rat MAL are ~100 times more sensitive to ETX than cells expressing similar levels of human MAL. Insertion of the FLAG sequence into the second extracellular loop of MAL abolishes ETX binding and cytotoxicity. ETX is known to bind specifically and with high affinity to intestinal epithelium, renal tubules, brain endothelial cells and myelin. We identify specific binding of ETX to these structures and additionally show binding to retinal microvasculature and the squamous epithelial cells of the sclera in wild-type mice. In contrast, there is a complete absence of ETX binding to tissues from MAL knockout (MAL-/-) mice. Furthermore, MAL-/- mice exhibit complete resistance to ETX at doses in excess of 1000 times the symptomatic dose for wild-type mice. We conclude that MAL is required for both ETX binding and cytotoxicity. PMID:25993478
Rumah, Kareem Rashid; Ma, Yinghua; Linden, Jennifer R; Oo, Myat Lin; Anrather, Josef; Schaeren-Wiemers, Nicole; Alonso, Miguel A; Fischetti, Vincent A; McClain, Mark S; Vartanian, Timothy
2015-05-01
Clostridium perfringens ε-toxin (ETX) is a potent pore-forming toxin responsible for a central nervous system (CNS) disease in ruminant animals with characteristics of blood-brain barrier (BBB) dysfunction and white matter injury. ETX has been proposed as a potential causative agent for Multiple Sclerosis (MS), a human disease that begins with BBB breakdown and injury to myelin forming cells of the CNS. The receptor for ETX is unknown. Here we show that both binding of ETX to mammalian cells and cytotoxicity requires the tetraspan proteolipid Myelin and Lymphocyte protein (MAL). While native Chinese Hamster Ovary (CHO) cells are resistant to ETX, exogenous expression of MAL in CHO cells confers both ETX binding and susceptibility to ETX-mediated cell death. Cells expressing rat MAL are ~100 times more sensitive to ETX than cells expressing similar levels of human MAL. Insertion of the FLAG sequence into the second extracellular loop of MAL abolishes ETX binding and cytotoxicity. ETX is known to bind specifically and with high affinity to intestinal epithelium, renal tubules, brain endothelial cells and myelin. We identify specific binding of ETX to these structures and additionally show binding to retinal microvasculature and the squamous epithelial cells of the sclera in wild-type mice. In contrast, there is a complete absence of ETX binding to tissues from MAL knockout (MAL-/-) mice. Furthermore, MAL-/- mice exhibit complete resistance to ETX at doses in excess of 1000 times the symptomatic dose for wild-type mice. We conclude that MAL is required for both ETX binding and cytotoxicity.
A comparison of 10 MHz and 20 MHz ultrasound probes in imaging the eye and orbit.
Hewick, S A; Fairhead, A C; Culy, J C; Atta, H R
2004-04-01
/aims: B-scan ultrasonography is an invaluable, versatile, non-invasive tool in ophthalmology. Recently, a "high frequency" contact 20 MHz probe has been introduced. B-scanning ultrasonography of orbital and ocular structures was performed with both a 10 MHz and the new 20 MHz probe, to evaluate what information was best obtained from each probe, and provide recommendations for the use of each. Patients were selected from routine ultrasound clinics at Aberdeen Royal Infirmary between 1 January 2002 and 1 August 2002. The vitreous, retina, choroid, sclera and, in the orbit, the extraocular muscles, optic nerve, and orbital fat were assessed with both the 10 MHz and 20 MHz probes. In the laboratory, using a "point target," the characteristics of the ultrasound beam at different distances from the probe were also assessed. The point target showed that focus was deeper and that the lateral, and to a lesser degree the axial, resolution are sharper with the 20 MHz probe, compared with the 10 MHz probe. In patients' eyes, highly reflective structures are seen at higher resolution with the 20 MHz probe. Imaging of lower intensity reflectors such as the vitreous and particles within it are seen better with the 10 MHz probe. Increased tissue attenuation was evident with the 20 MHz probe. The 20 MHz probe has a superior resolution and can be used to better detect details at the posterior pole and in the orbit. The 10 MHz probe can be used to examine low intensity scatterers, such as the vitreous humour, that cannot be seen using a higher frequency probe.
Khakshoor, Hamid; Razavi, Mohammad Etezad; Daneshvar, Ramin; Shakeri, Mohammad Taghi; Ghate, Majid Farrokh; Ghooshkhanehi, Haleh
2010-08-01
To evaluate and compare the recurrence rates and complications between 2 therapeutic methods for primary pterygium: subconjunctival injection of mitomycin C (MMC) 1 month before bare scleral excision and conjunctival rotational flap with intraoperative MMC use. Prospective, interventional, randomized clinical trial. setting: Institutional clinical trial in a tertiary, specialty eye hospital. study population and intervention: We included 82 eyes diagnosed with primary pterygium and randomly allocated them into 2 groups. Group A consisted of 36 eyes treated with subconjunctival injection of 0.02% MMC 1 month before bare scleral excision, and group B comprised 46 eyes that underwent conjunctival rotational flap with intraoperative 0.02% MMC for 2 minutes. Follow-up periods were at least 12 months (range, 12 to 18 months). main outcome measure: Recurrence and complication rate in each arm of study. During the 1-year follow-up, 2 cases of clinical recurrence in third and sixth month of follow-up occurred in group B (recurrence rate, 4.3%). In group A, there was no clinically significant recurrence, but 2 cases of hypovascularity and whitening of sclera at the site of pterygium excision was observed. There was no other serious complication. There was no statistically significant difference between groups for recurrence rate, mean age, sex, or pterygium area. Subconjunctival injection of MMC 0.02% (0.1 ml of 0.02% solution) 1 month before bare scleral excision is a quick, easy, and safe surgical procedure and is at least as effective as conjunctival rotational flap with intraoperative MMC for 2 minutes. Copyright (c) 2010 Elsevier Inc. All rights reserved.
Ocular Manifestations of Oblique Facial Clefts
Ortube, Maria Carolina; Dipple, Katrina; Setoguchi, Yoshio; Kawamoto, Henry K.; Demer, Joseph L.
2014-01-01
Introduction In the Tessier classification, craniofacial clefts are numbered from 0 to 14 and extend along constant axes through the eyebrows, eyelids, maxilla, nostrils, and the lips. We studied a patient with bilateral cleft 10 associated with ocular abnormalities. Method Clinical report with orbital and cranial computed tomography. Results After pregnancy complicated by oligohydramnios, digoxin, and lisinopril exposure, a boy was born with facial and ocular dysmorphism. Examination at age 26 months showed bilateral epibulbar dermoids, covering half the corneal surface, and unilateral morning glory anomaly of the optic nerve. Ductions of the right eye were normal, but the left eye had severely impaired ductions in all directions, left hypotropia, and esotropia. Under anesthesia, the left eye could not be rotated freely in any direction. Bilateral Tessier cleft number 10 was implicated by the presence of colobomata of the middle third of the upper eyelids and eyebrows. As the cleft continued into the hairline, there was marked anterior scalp alopecia. Computed x-ray tomography showed a left middle cranial fossa arachnoid cyst and calcification of the reflected tendon of the superior oblique muscle, trochlea, and underlying sclera, with downward and lateral globe displacement. Discussion Tessier 10 clefts are very rare and usually associated with encephalocele. Bilateral 10 clefts have not been reported previously. In this case, there was coexisting unilateral morning glory anomaly and arachnoid cyst of the left middle cranial fossa but no encephalocele. Conclusions Bilateral Tessier facial cleft 10 may be associated with alopecia, morning glory anomaly, epibulbar dermoids, arachnoid cyst, and restrictive strabismus. PMID:20856062
Ketorolac inhibits choroidal neovascularization by suppression of retinal VEGF
Kim, Stephen J.; Toma, Hassanain S.; Barnett, Joshua M.; Penn, John S.
2011-01-01
We assessed the effect of topical ketorolac on laser-induced choroidal neovascularization (CNV), measured retinal PGE2 and VEGF levels after laser treatment, and determined the effect of ketorolac on PGE2 and VEGF production. Six laser burns were placed in eyes of rats which then received topical ketorolac 0.4% or artificial tears four times daily until sacrifice. Fluorescein angiography (FA) was performed at 2 and 3 weeks and retinal pigment epithelium-choroid-sclera flat mounts were prepared. The retina and vitreous were isolated at 1, 3, 5, 7, and 14 days after laser treatment and tested for VEGF and PGE2. Additional animals were lasered and treated with topical ketorolac or artificial tears and tested at 3 and 7 days for retinal and vitreous VEGF and PGE2. Ketorolac reduced CNV on FA by 27% at 2 weeks (P < 0.001) and 25% at 3 weeks (P < 0.001). Baseline retina and vitreous PGE2 levels were 29.4 μg/g and 16.5 μg/g respectively, and reached 51.2 μg/g and 26.9 μg/g respectively, 24 h after laser treatment (P < 0.05). Retinal VEGF level was 781 pg/g 24 h after laser treatment and reached 931 pg/g by 7 days (P < 0.01). Ketorolac reduced retinal PGE2 by 35% at 3 days (P < 0.05) and 29% at 7 days (P < 0.001) and retinal VEGF by 31% at 3 days (P = 0.10) and 19% at 7 days (P < 0.001). Topical ketorolac inhibited CNV and suppressed retinal PGE2 and VEGF production. PMID:20659449
Diagnostic value of neuro-ophthalmological signs in cases of Chiari I malformation.
Bekerman, Inessa; Sigal, Tal; Kimiagar, Itzhak; Almer, Zina Evy; Vaiman, Michael
2016-12-01
Our purpose was to evaluate the diagnostic value of measuring diameters of optic nerve sheath (ONSD), presence/absence of papilledema, tortuosity of the optic nerve, flattening of the posterior sclera, and intraocular protrusion of the prelaminar optic nerve for intracranial pressure assessment in cases of Chiari I malformation. In a retrospective study, MRI data of 37 consecutive pediatric patients with Chiari malformation and data of 400 patients without intracranial pathology were compared and analyzed. ONSDs were measured at the point where the ophthalmic artery crosses the optic nerve (anatomical landmark). The correlation analysis was performed with clinical findings, gender, age, papilledema, and other neuro-ophthalmological findings. ONSD was enlarged in 38 % of cases of Chiari malformation. The enlargement was bilateral, no correlation with age or gender was found (p = 0.67 and p = 0.76, respectively). The presence of papilledema was detected in 19 % of cases presenting less valuable diagnostic sign if compared with ONSD. The tortuosity of the optic nerve was found in 22 % of cases, but in three patients, it was unilateral. All patients with enlarged ONSD and other neuro-ophthalmological signs present were treated surgically, while most of the patients without these signs (20/23) were treated conservatively. In majority of pediatric cases of Chiari malformation, the ONSD is not enlarged and other neuro-ophthalmological signs are not present. Detecting the enlarged ONSD and other neuro-ophthalmological signs in cases of Chiari malformation may indicate the elevated intracranial pressure and necessity for urgent surgical intervention.
Aldrich, Benjamin T; Stockman, Adam M; Freiburger, Monica J; Shinkunas, Todd J; Burckart, Kimberlee A; Schmidt, Gregory A; Reed, Cynthia R; Zimmerman, M Bridget; Goins, Kenneth M; Wagoner, Michael D; Greiner, Mark A
2015-12-01
To develop a method based on identification of the widest region of the surgical limbus that can yield quick and accurate orientation of excised human donor corneas. Corneoscleral tissue from donors 49 to 75 years old was marked at the temporal sclera at the time of recovery. Digital images obtained from 20 corneas stored in viewing chambers, retroilluminated and viewed from the endothelial side, were used to quantify the per-degree radial width of the surgical limbus, defined as the distance from the scleral spur to clear cornea. To evaluate differences in radial width among regions, measurements were compared with the intracorneal mean limbal width, and a per-degree z-score was calculated by averaging among corneas. Using images of corneas with the temporal mark masked and the sidedness known, 6 observers were subjected to a blinded trial of 10 corneas to determine the central point of the widest limbal region of each cornea. Compared with the intracorneal mean, the mean radial width of the surgical limbus was greatest in the superior quadrant, and the difference compared with the inferior, nasal, and temporal quadrants was significant (P < 0.0001). The superior region was identified with 100% accuracy in blinded trials. The average absolute difference between the predicted and actual central point of the superior limbus was 9.75 ± 0.30 degrees. The radial width of the surgical limbus is greatest in the superior region of the cornea and can be used as a diagnostic feature to orient donor corneal tissue.
Singh, Rupesh; Rajaraman, Srinivas; Balasubramanian, Madhusudhanan
2017-10-01
A novel nanoparticle mediated methodology for laser photocoagulation of the inner retina to achieve tissue selective treatment is presented. Transport of 527, 577, and 810 nm laser, heat deposition, and eventual thermal damage in vitreous, retina, RPE, choroid, and sclera were modeled using Bouguer-Beer-Lambert law of absorption and solved numerically using the finite volume method. Nanoparticles were designed using Mie theory of scattering. Performance of the new photocoagulation strategy using gold nanospheres and gold-silica nanoshells was compared with that of conventional methods without nanoparticles. For experimental validation, vitreous cavity of ex vivo porcine eyes was infused with gold nanospheres. After ~6 h of nanoparticle diffusion, the porcine retina was irradiated with a green laser and imaged simultaneously using a spectral domain optical coherence tomography (Spectralis SD-OCT, Heidelberg Engineering). Our computational model predicted a significant spatial shift in the peak temperature from RPE to the inner retinal region when infused with nanoparticles. Arrhenius thermal damage in the mid-retinal location was achieved in ~14 ms for 527 nm laser thereby reducing the irradiation duration by ~30 ms compared with the treatment without nanoparticles. In ex vivo porcine eyes infused with gold nanospheres, SD-OCT retinal images revealed a lower thermal damage and expansion at RPE due to laser photocoagulation. Nanoparticle infused laser photocoagulation strategy provided a selective inner retinal thermal damage with significant decrease in laser power and laser exposure time. The proposed treatment strategy shows possibilities for an efficient and highly selective inner retinal laser treatment.
Software-based evaluation of toric IOL orientation in a multicenter clinical study.
Kasthurirangan, Sanjeev; Feuchter, Lucas; Smith, Pamela; Nixon, Donald
2014-12-01
To evaluate the rotational stability of a new one-piece hydrophobic acrylic toric intraocular lens (IOL) using a custom-developed software for analysis of slit-lamp photographs. In a prospective, multicenter study, 174 eyes were implanted with the TECNIS Toric IOL (Abbott Medical Optics, Inc., Santa Ana, CA). A custom-developed software was used to analyze high-resolution slit-lamp photographs of 156 eyes taken at day 1 (baseline) and 1, 3, and 6 months postoperatively. The software uses iris and sclera landmarks to align the baseline image and later images for comparison. Validation of software was performed through repeated analyses of protractor images rotated from 0.1° to 10.0° and randomly selected photographs of 20 eyes. Software validation showed precision (repeatability plus reproducibility variation) of 0.02° using protractor images and 2.22° using slit-lamp photographs. Good quality slit-lamp images and clear landmarks were necessary for precise measurements. At 6 months, 94.2% of eyes had 5° or less change in IOL orientation versus baseline; only 2 eyes (1.4%) had axis shift greater than 30°. Most eyes were within 5° or less of rotation between 1 and 3 months (92.9%) and 3 and 6 months (94.1%). Mean absolute axis change (± standard deviation) from 1 day to 6 months was 2.70° ± 5.51°. The new custom software was precise and quick in analyzing slit-lamp photographs to determine postoperative toric IOL rotation. Copyright 2014, SLACK Incorporated.
Kanda, Hiroyuki; Morimoto, Takeshi; Fujikado, Takashi; Tano, Yasuo; Fukuda, Yutaka; Sawai, Hajime
2004-02-01
Assessment of a novel method of retinal stimulation, known as suprachoroidal-transretinal stimulation (STS), which was designed to minimize insult to the retina by implantation of stimulating electrodes for artificial vision. In 17 normal hooded rats and 12 Royal College of Surgeons (RCS) rats, a small area of the retina was focally stimulated with electric currents through an anode placed on the fenestrated sclera and a cathode inserted into the vitreous chamber. Evoked potentials (EPs) in response to STS were recorded from the surface of the superior colliculus (SC) with a silver-ball electrode, and their physiological properties and localization were studied. In both normal and RCS rats, STS elicited triphasic EPs that were vastly diminished by changing polarity of stimulating electrodes and abolished by transecting the optic nerve. The threshold intensity (C) of the EP response to STS was approximately 7.2 +/- 2.8 nC in normal and 12.9 +/- 7.7 nC in RCS rats. The responses to minimal STS were localized in an area on the SC surface measuring 0.12 +/- 0.07 mm(2) in normal rats and 0.24 +/- 0.12 mm(2) in RCS rats. The responsive area corresponded retinotopically to the retinal region immediately beneath the anodic stimulating electrode. STS is less invasive in the retina than stimulation through epiretinal or subretinal implants. STS can generate focal excitation in retinal ganglion cells in normal animals and in those with degenerated photoreceptors, which suggests that this method of retinal stimulation is suitable for artificial vision.
Arellano-Ganem, M G; Zuazo, F; González, M; Abdala, A; Olvera-Morales, O; Tovilla-Canales, J L; Nava-Castañeda, Á
2017-02-01
Evisceration is currently becoming the technique of choice in the treatment of certain eye diseases, including, among others, painful blind eye and endophthalmitis. The most widely used implants are currently the hydroxyapatite and porous polyethylene for the rehabilitation of the anophthalmic socket. To describe the indications, type of implant material used, and complications in evisceration surgery. A retrospective, observational, descriptive study based on clinical records of patients that underwent evisceration between 2008 and 2015 in the Instituto Fundación Conde de Valenciana, Mexico. A total of 186 evisceration surgeries were performed, of which 52.7% of the patients were men. The mean age was 54 years. The right eye was eviscerated in 53% of cases, and 79.2% had a vision of no light perception. Most patients had preoperative pain. The most common diagnosis for which evisceration was performed was endophthalmitis. Phthisis bulbi was reported in 20 eyes. A primary implant was inserted in 86.81% of the cases, with 34.81% of the implants being made of porous polyethylene. Four cases showed extrusion of the implant, with 2 cases of porous polyethylene. The ocular prosthesis was tolerated in 91% of cases. There were no cases of sympathetic ophthalmia. Evisceration is shown to be a good alternative to enucleation in cases where the sclera can be preserved, showing a low incidence of sympathetic ophthalmia. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.
Factors Influencing Central Lamina Cribrosa Depth: A Multicenter Study
Luo, Haomin; Yang, Hongli; Gardiner, Stuart K.; Hardin, Christy; Sharpe, Glen P.; Caprioli, Joseph; Demirel, Shaban; Girkin, Christopher A.; Liebmann, Jeffrey M.; Mardin, Christian Y.; Quigley, Harry A.; Scheuerle, Alexander F.; Fortune, Brad; Chauhan, Balwantray C.; Burgoyne, Claude F.
2018-01-01
Purpose To quantify the influence of ocular and demographic factors on central laminar depth (LD) in healthy participants. Methods A total of 362 normal subjects underwent optical coherence tomography (OCT) enhanced depth imaging of the optic nerve head (ONH) with a 24 radial B-scan pattern aligned to the fovea–to–Bruch's membrane opening (BMO) axis. BMO, anterior lamina, anterior scleral canal opening (ASCO), Bruch's membrane (BM), and the peripapillary scleral surface were manually segmented. The extent of laminar segmentation was quantified within 72 ASCO subsectors. Central LD was quantified relative to four reference planes: BMO, ASCO, BM, and scleral. The effects of age, sex, ethnicity, IOP, BMO area, ASCO area, and axial length on LD were assessed. Results Laminar visibility was most consistent within the central ASCO (median 89%, range, 69%–95%). LDBMO and LDBM were significantly shallower in eyes with greater age, BMO area, and axial length and in females. LDASCO was shallower in eyes with greater ASCO area and axial length and in European and Hispanic descent compared to African descent eyes. LDSclera behaved similarly, but was not associated with axial length. BMO and ASCO area were not different between African descent and European descent eyes. Conclusions Central LD was deeper in African descent eyes and influenced least by age, axial length, and sex, but more by ASCO area, when measured relative to the ASCO and sclera. However, the magnitude of these effects for all four reference planes was small, and their clinical importance in the detection of glaucoma and its progression remains to be determined. PMID:29847642
Clinicopathologic correlation of chorioretinitis sclopetaria.
Dubovy, S R; Guyton, D L; Green, W R
1997-01-01
To report the clinicopathologic features in the eye of a patient who sustained a traumatic chorioretinal rupture from a gunshot wound to the orbit, chorioretinitis sclopetaria, with clinical follow up of more than 20 years. The patient was studied ophthalmoscopically and by fluorescein angiography after the trauma and was seen intermittently thereafter. The eyes were obtained postmortem; sections of the central portion of the right eye, including the macula and optic nerve head, and the inferior cap were examined by light microscopy. Histopathologic study of the right eye showed partial loss of the nerve fiber and ganglion cell layers in the macular area, temporal peripapillary and macular loss of the photoreceptors with hypertrophy and hyperplasia of the retinal pigment epithelium, an epiretinal membrane, and three defects in Bruch's membrane. Inferiorly, there was a 5-mm defect in choroid, Bruch's membrane, and retina. These structures were replaced by a loose and dense fibrous connective tissue. The sclera and a long posterior ciliary nerve remained intact. A thin fibrovascular tissue from the choroid extended into the subretinal space where it was covered by retinal pigment epithelium and thickened basement membrane in the posterior aspect of the inferior lesion. Marked hemiatrophy of the optic nerve was present. The clinicopathologic features of chorioretinitis sclopetaria include direct traumatic chorioretinal rupture followed by marked fibrovascular proliferation with variable replacement of choroid and retina with no retinal detachment. Posteriorly, indirect macular choroidal ruptures with hyperplasia and migration of the retinal pigment epithelium into the retina and choroid, epiretinal membrane formation, loss of photoreceptors, and marked hemiatrophy of the optic nerve were present.
Presumed post-traumatic ocular chondrosarcoma with intrathoracic metastases in a cat.
Moreira, Matheus V L; de Andrade, Maria C; Fulgêncio, Gustavo O; Langohr, Ingeborg M; Ecco, Roselene
2017-10-03
An indoor-only, 5-year-old, spayed female domestic shorthair cat presented for an ophthalmic examination of the left eye. An intraocular tumor with secondary glaucoma and blindness was diagnosed; the globe was enucleated and sent for histopathological examination. Gross examination revealed a solid white mass filling the entire vitreous space and replacing the iris and ciliary body. The lens and retina appeared to be similarly replaced by the neoplasm. Histological examination revealed a complete loss of the internal ocular structures, with a ruptured capsule as the only remnant of the lens within an extensive malignant mesenchymal neoplastic cell proliferation. The cells were polygonal, with well-defined cytoplasmic borders and abundant weakly basophilic cytoplasm, embedded within the islands of chondroid matrix. No neoplastic invasion of the sclera was apparent. The animal died 6 months after the enucleation due to respiratory distress. Gross examination revealed numerous firm, white to tan nodular masses with smooth to mildly irregular surfaces dispersed throughout the parietal pleura, thoracic surface of the diaphragm, tracheobronchial and mediastinal lymph nodes, pericardium, and lungs. On cross-section, the neoplastic nodules were solid and variably translucent, resembling hyaline cartilage. Histologically, these nodules were similar to the neoplasm identified earlier in the left globe. Metastasis of post-traumatic ocular chondrosarcoma has not yet been described in cats. This is therefore believed to be the first report of metastases of this type of neoplasm in cats. This case adds to the limited set of data on the outcome of this type of tumor. © 2017 American College of Veterinary Ophthalmologists.
Ocular oxygen consumption during vitreoperfusion in the cat.
Blair, N P
2000-01-01
Little is known about the total ocular oxygen consumption rate (QO2) in human diseases. Reductions in QO2 may indicate the amount of tissue loss produced by conditions such as retinal ischemia. We sought a method to estimate QO2 that eventually could be used in patients during vitrectomy surgery. We performed vitreoperfusion (perfusion of the vitreous cavity after vitrectomy) in 22 cat eyes with no ocular blood flow. The solution contained nutrients and a high partial pressure of oxygen (PO2). In 8 eyes we placed an oxygen electrode on the sclera, choroid, or outer retina to evaluate oxygen delivery from the vitreoperfusion solution (group 1). In 8 eyes the retinas were undisturbed (group 2), and in 6 eyes we excised the retinas (group 3). In groups 2 and 3 we estimated QO2 from the temporal decline of PO2 in the vitreoperfusion solution according to a pharmacokinetic model. Group 1 demonstrated oxygenation of the entire retina. The means and standard deviations of QO2 were 3.2 +/- 0.8 and 0.4 +/- 0.7 microL/min in groups 2 and 3, respectively, the difference being the retinal contribution, 88%. In group 2, metabolism accounted for an average of 82% of the oxygen loss from the vitreoperfusion solution, whereas flow and diffusion accounted for 13% and 5%, respectively. Ocular oxygen consumption can be estimated by means of vitreoperfusion. Further developments may allow measurements in patients during vitreous surgery to clarify the pathophysiology of their diseases and assess the amount of retinal tissue that has been lost.
Fangueiro, Joana F; Calpena, Ana C; Clares, Beatriz; Andreani, Tatiana; Egea, Maria A; Veiga, Francisco J; Garcia, Maria L; Silva, Amélia M; Souto, Eliana B
2016-04-11
Cationic lipid nanoparticles (LNs) have been tested for sustained release and site-specific targeting of epigallocatechin gallate (EGCG), a potential polyphenol with improved pharmacological profile for the treatment of ocular pathologies, such as age-related macular edema, diabetic retinopathy, and inflammatory disorders. Cationic EGCG-LNs were produced by double-emulsion technique; the in vitro release study was performed in a dialysis bag, followed by the drug assay using a previously validated RP-HPLC method. In vitro HET-CAM study was carried out using chicken embryos to determine the potential risk of irritation of the developed formulations. Ex vivo permeation profile was assessed using rabbit cornea and sclera isolated and mounted in Franz diffusion cells. The results show that the use of cationic LNs provides a prolonged EGCG release, following a Boltzmann sigmoidal profile. In addition, EGCG was successfully quantified in both tested ocular tissues, demonstrating the ability of these formulations to reach both anterior and posterior segment of the eye. The pharmacokinetic study of the corneal permeation showed a first order kinetics for both cationic formulations, while EGCG-cetyltrimethylammonium bromide (CTAB) LNs followed a Boltzmann sigmoidal profile and EGCG-dimethyldioctadecylammonium bromide (DDAB) LNs a first order profile. Our studies also proved the safety and non-irritant nature of the developed LNs. Thus, loading EGCG in cationic LNs is recognised as a promising strategy for the treatment of ocular diseases related to anti-oxidant and anti-inflammatory pathways. Copyright © 2016 Elsevier B.V. All rights reserved.
Gonioscopic ab interno laser sclerostomy. A pilot study in glaucoma patients.
Latina, M A; Melamed, S; March, W F; Kass, M A; Kolker, A E
1992-11-01
The purpose of this study is to evaluate the safety and efficacy of gonioscopic ab interno laser sclerostomy (GLS) in patients with glaucoma. The technique of GLS involves iontophoresis of methylene blue dye (1%) at the limbus to focally dye the sclera and to provide subsequent delivery of 10-microsecond pulsed laser energy to the dyed area through a goniolens. The laser emits at 660 nm, a wavelength that is maximally absorbed by the methylene blue dye. Patients were evaluated for fistula formation, intraocular pressure (IOP) reduction, and adverse sequelae. Thirty-eight treatments were performed in 35 eyes. Successful complete sclerostomies were achieved in 21 eyes (55%), which was associated with an acute mean reduction in IOP of 23 mmHg. Mean preoperative IOP for all patients was 35 mmHg, and 1 hour after treatment it was reduced to 18.5 mmHg. In 4 of the 38 treatments, there was no acute IOP reduction, and these eyes were judged as failures. The mean follow-up time was 8.2 months with a maximum follow-up of 15 months. By 9 months, 50% of patients had an IOP of 22 mmHg or lower. The number of antiglaucoma medications decreased from 3.1 to 1.7 for all eyes over the 15-month follow-up period. Hyphemas (13%) were the only major complication, and these resolved spontaneously. In only one case did the IOP increase after the procedure. The results of this trial indicate that GLS is technically feasible, and preliminary results of IOP control are promising.