In vitro effects of preserved and unpreserved anti-allergic drugs on human corneal epithelial cells.

PubMed

Guzman-Aranguez, Ana; Calvo, Patricia; Ropero, Inés; Pintor, Jesús

2014-11-01

Treatment with topical eye drops for long-standing ocular diseases like allergy can induce detrimental side effects. The purpose of this study was to investigate in vitro cytotoxicity of commercially preserved and unpreserved anti-allergic eye drops on the viability and barrier function of monolayer and stratified human corneal-limbal epithelial cells. Cells were treated with unpreserved ketotifen solution, benzalkonium chloride (BAC)-containing anti-allergic drugs (ketotifen, olopatadine, levocabastine) as well as BAC alone. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to determine cell viability. Effects of compounds on barrier function were analyzed measuring transepithelial electrical resistance (TEER) to determine paracellular permeability and rose bengal assays to evaluate transcellular barrier formation. The BAC-preserved anti-allergic formulations and BAC alone significantly reduced cell viability, monolayer cultures being more sensitive to damage by these solutions. Unpreserved ketotifen induced the least diminution in cell viability. The extent of decrease of cell viability was clearly dependent of BAC presence, but it was also affected by the different types of drugs when the concentration of BAC was low and the short time of exposure. Treatment with BAC-containing anti-allergic drugs and BAC alone resulted in increased paracellular permeability and loss of transcellular barrier function as indicated by TEER measurement and rose bengal assays. The presence of the preservative BAC in anti-allergic eye drop formulations contributes importantly to the cytotoxic effects induced by these compounds. Stratified cell cultures seem to be a more relevant model for toxicity evaluation induced on the ocular surface epithelia than monolayer cultures.

Corneal critical barrier against the penetration of dexamethasone and lomefloxacin hydrochloride: evaluation by the activation energy for drug partition and diffusion in cornea.

PubMed

Yasueda, Shin-ichi; Higashiyama, Masayo; Yamaguchi, Masazumi; Isowaki, Akiharu; Ohtori, Akira

2007-08-01

The cornea is a solid barrier against drug permeation. We searched the critical barrier of corneal drug permeation using a hydrophobic drug, dexamethasone (DM), and a hydrophilic drug, lomefloxacin hydrochloride (LFLX). The activation energies for permeability of DM and LFLX across the intact cornea were 88.0 and 42.1 kJ/mol, respectively. Their activation energies for permeability across the cornea without epithelium decreased to 33.1 and 16.6 kJ/mol, respectively. The results show that epithelium is the critical barrier on the cornea against the permeation of a hydrophobic drug of DM as well as a hydrophilic drug of LFLX. The activation energy of partition for DM (66.8 kJ/mol) was approximately 3-fold larger than that of diffusion (21.2 kJ/mol). The results indicate that the partition for the hydrophobic drug of DM to the corneal epithelium is the primary barrier. Thermodynamic evaluation of activation energy for the drug permeation parameters is a good approach to investigate the mechanism of drug permeability.

ROCK Inhibitor Enhances Adhesion and Wound Healing of Human Corneal Endothelial Cells

PubMed Central

Pipparelli, Aurélien; Arsenijevic, Yvan; Thuret, Gilles; Gain, Philippe

2013-01-01

Maintenance of corneal transparency is crucial for vision and depends mainly on the endothelium, a non-proliferative monolayer of cells covering the inner part of the cornea. When endothelial cell density falls below a critical threshold, the barrier and “pump” functions of the endothelium are compromised which results in corneal oedema and loss of visual acuity. The conventional treatment for such severe disorder is corneal graft. Unfortunately, there is a worldwide shortage of donor corneas, necessitating amelioration of tissue survival and storage after harvesting. Recently it was reported that the ROCK inhibitor Y-27632 promotes adhesion, inhibits apoptosis, increases the number of proliferating monkey corneal endothelial cells in vitro and enhance corneal endothelial wound healing both in vitro and in vivo in animal models. Using organ culture human cornea (N = 34), the effect of ROCK inhibitor was evaluated in vitro and ex vivo. Toxicity, corneal endothelial cell density, cell proliferation, apoptosis, cell morphometry, adhesion and wound healing process were evaluated by live/dead assay standard cell counting method, EdU labelling, Ki67, Caspase3, Zo-1 and Actin immunostaining. We demonstrated for the first time in human corneal endothelial cells ex vivo and in vitro, that ROCK inhibitor did not induce any toxicity effect and did not alter cell viability. ROCK inhibitor treatment did not induce human corneal endothelial cells proliferation. However, ROCK inhibitor significantly enhanced adhesion and wound healing. The present study shows that the selective ROCK inhibitor Y-27632 has no effect on human corneal endothelial cells proliferative capacities, but alters cellular behaviours. It induces changes in cell shape, increases cell adhesion and enhances wound healing ex vivo and in vitro. Its absence of toxicity, as demonstrated herein, is relevant for its use in human therapy. PMID:23626771

On the barrier properties of the cornea: a microscopy study of the penetration of fluorescently labeled nanoparticles, polymers, and sodium fluorescein.

PubMed

Mun, Ellina A; Morrison, Peter W J; Williams, Adrian C; Khutoryanskiy, Vitaliy V

2014-10-06

Overcoming the natural defensive barrier functions of the eye remains one of the greatest challenges of ocular drug delivery. Cornea is a chemical and mechanical barrier preventing the passage of any foreign bodies including drugs into the eye, but the factors limiting penetration of permeants and nanoparticulate drug delivery systems through the cornea are still not fully understood. In this study, we investigate these barrier properties of the cornea using thiolated and PEGylated (750 and 5000 Da) nanoparticles, sodium fluorescein, and two linear polymers (dextran and polyethylene glycol). Experiments used intact bovine cornea in addition to bovine cornea de-epithelialized or tissues pretreated with cyclodextrin. It was shown that corneal epithelium is the major barrier for permeation; pretreatment of the cornea with β-cyclodextrin provides higher permeation of low molecular weight compounds, such as sodium fluorescein, but does not enhance penetration of nanoparticles and larger molecules. Studying penetration of thiolated and PEGylated (750 and 5000 Da) nanoparticles into the de-epithelialized ocular tissue revealed that interactions between corneal surface and thiol groups of nanoparticles were more significant determinants of penetration than particle size (for the sizes used here). PEGylation with polyethylene glycol of a higher molecular weight (5000 Da) allows penetration of nanoparticles into the stroma, which proceeds gradually, after an initial 1 h lag phase.

In Vitro Effects of Preserved and Unpreserved Anti-Allergic Drugs on Human Corneal Epithelial Cells

PubMed Central

Calvo, Patricia; Ropero, Inés; Pintor, Jesús

2014-01-01

Abstract Purpose: Treatment with topical eye drops for long-standing ocular diseases like allergy can induce detrimental side effects. The purpose of this study was to investigate in vitro cytotoxicity of commercially preserved and unpreserved anti-allergic eye drops on the viability and barrier function of monolayer and stratified human corneal-limbal epithelial cells. Methods: Cells were treated with unpreserved ketotifen solution, benzalkonium chloride (BAC)-containing anti-allergic drugs (ketotifen, olopatadine, levocabastine) as well as BAC alone. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to determine cell viability. Effects of compounds on barrier function were analyzed measuring transepithelial electrical resistance (TEER) to determine paracellular permeability and rose bengal assays to evaluate transcellular barrier formation. Results: The BAC-preserved anti-allergic formulations and BAC alone significantly reduced cell viability, monolayer cultures being more sensitive to damage by these solutions. Unpreserved ketotifen induced the least diminution in cell viability. The extent of decrease of cell viability was clearly dependent of BAC presence, but it was also affected by the different types of drugs when the concentration of BAC was low and the short time of exposure. Treatment with BAC-containing anti-allergic drugs and BAC alone resulted in increased paracellular permeability and loss of transcellular barrier function as indicated by TEER measurement and rose bengal assays. Conclusions: The presence of the preservative BAC in anti-allergic eye drop formulations contributes importantly to the cytotoxic effects induced by these compounds. Stratified cell cultures seem to be a more relevant model for toxicity evaluation induced on the ocular surface epithelia than monolayer cultures. PMID:25100331

Wound-Healing Studies in Cornea and Skin: Parallels, Differences and Opportunities

PubMed Central

Bukowiecki, Anne; Hos, Deniz; Cursiefen, Claus; Eming, Sabine A.

2017-01-01

The cornea and the skin are both organs that provide the outer barrier of the body. Both tissues have developed intrinsic mechanisms that protect the organism from a wide range of external threats, but at the same time also enable rapid restoration of tissue integrity and organ-specific function. The easy accessibility makes the skin an attractive model system to study tissue damage and repair. Findings from skin research have contributed to unravelling novel fundamental principles in regenerative biology and the repair of other epithelial-mesenchymal tissues, such as the cornea. Following barrier disruption, the influx of inflammatory cells, myofibroblast differentiation, extracellular matrix synthesis and scar formation present parallel repair mechanisms in cornea and skin wound healing. Yet, capillary sprouting, while pivotal in proper skin wound healing, is a process that is rather associated with pathological repair of the cornea. Understanding the parallels and differences of the cellular and molecular networks that coordinate the wound healing response in skin and cornea are likely of mutual importance for both organs with regard to the development of regenerative therapies and understanding of the disease pathologies that affect epithelial-mesenchymal interactions. Here, we review the principal events in corneal wound healing and the mechanisms to restore corneal transparency and barrier function. We also refer to skin repair mechanisms and their potential implications for regenerative processes in the cornea. PMID:28604651

Wound-Healing Studies in Cornea and Skin: Parallels, Differences and Opportunities.

PubMed

Bukowiecki, Anne; Hos, Deniz; Cursiefen, Claus; Eming, Sabine A

2017-06-12

The cornea and the skin are both organs that provide the outer barrier of the body. Both tissues have developed intrinsic mechanisms that protect the organism from a wide range of external threats, but at the same time also enable rapid restoration of tissue integrity and organ-specific function. The easy accessibility makes the skin an attractive model system to study tissue damage and repair. Findings from skin research have contributed to unravelling novel fundamental principles in regenerative biology and the repair of other epithelial-mesenchymal tissues, such as the cornea. Following barrier disruption, the influx of inflammatory cells, myofibroblast differentiation, extracellular matrix synthesis and scar formation present parallel repair mechanisms in cornea and skin wound healing. Yet, capillary sprouting, while pivotal in proper skin wound healing, is a process that is rather associated with pathological repair of the cornea. Understanding the parallels and differences of the cellular and molecular networks that coordinate the wound healing response in skin and cornea are likely of mutual importance for both organs with regard to the development of regenerative therapies and understanding of the disease pathologies that affect epithelial-mesenchymal interactions. Here, we review the principal events in corneal wound healing and the mechanisms to restore corneal transparency and barrier function. We also refer to skin repair mechanisms and their potential implications for regenerative processes in the cornea.

Diadenosine tetraphosphate improves adrenergic anti-glaucomatous drug delivery and efficiency.

PubMed

Loma, Patricia; Guzman-Aranguez, Ana; Perez de Lara, Maria Jesus; Pintor, Jesus

2015-05-01

The effect of the dinucleotide P(1), P(4)-Di (adenosine-5') tetraphosphate (Ap4A) in improving adrenergic anti-glaucomatous delivery by modifying the tight junction proteins of the corneal epithelium was evaluated. Stratified human corneal epithelial cells (HCLE) were treated with Ap4A (100 μM) for 5 min and TJ protein levels and barrier function were analysed by western blotting and transepithelial electrical resistance (TEER), respectively. Western blot experiments showed a significant reduction at 2 h (45% reduction of ZO-1 and 65% reduction of occludin protein levels) as compared to non-treated (control) cells. Two hours after Ap4A treatment, TEER values were significantly reduced (65% as compared to control levels (p < 0.001)), indicating an increase in corneal barrier permeability. Topical application of Ap4A in New Zealand white rabbits two hours before the instillation of the hypotensor compounds (the α2-adrenergic receptor agonist, brimonidine and the β-adrenergic receptor antagonist, timolol), improved the delivery of these compounds to the anterior chamber as well as their hypotensive action on the intraocular pressure. The results obtained showed that, when Ap4A was topically applied two hours before the adrenergic compounds, the concentration of brimonidine in the aqueous humour increased from 64.3 ± 5.3 nM to 240.6 ± 8.6 nM and from 58.9 ± 9.2 nM to 183.7 ± 6.8 nM in the case of timolol, which also produces a more profound effect on IOP. Therefore, Ap4A treatment results in a better entrance of adrenergic anti-glaucomatous compounds within the eye and consequently improved therapeutic efficiency by increasing corneal epithelial barrier permeability. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Effect of Rebamipide on Ocular Surface Disorders Induced by Latanoprost and Timolol in Glaucoma Patients.

PubMed

Tokuda, Naoto; Kitaoka, Yasushi; Matsuzawa, Akiko; Miyamoto, Junsuke; Sakae, Shinsuke; Munemasa, Yasunari; Takagi, Hitoshi

2015-01-01

Purpose. To examine the efficacy of ophthalmic rebamipide suspensions on ocular surface disorders induced by antiglaucoma eye drops. Patients and Methods. Forty eyes of 40 patients receiving latanoprost (0.005%) and timolol (0.5%) were included in this randomized prospective study. The patients were randomly divided into two groups (n = 20): the rebamipide-treated group and control group. Changes in intraocular pressure, tear film break-up time (TBUT), and corneal epithelial barrier function were evaluated at baseline, 4 weeks, and 8 weeks after rebamipide administration. Furthermore, superficial punctate keratopathy severity was evaluated by scoring the lesion area and density. Results. There was no significant difference in intraocular pressure before and after rebamipide treatment. However, corneal epithelial barrier function improved significantly 4 and 8 weeks after rebamipide treatment. TBUT was partially, but significantly, increased (P = 0.02) 8 weeks after rebamipide treatment, whereas no significant change was observed at 4 weeks. Additionally, a significant decrease in area and density of keratopathy was observed 8 weeks after rebamipide treatment but not at 4 weeks. The control group showed no significant difference compared to baseline. Conclusions. Our data suggests that rebamipide treatment may reduce the occurrence of drug-induced ocular surface disorder.

A novel closed cell culture device for fabrication of corneal epithelial cell sheets.

PubMed

Nakajima, Ryota; Kobayashi, Toyoshige; Moriya, Noboru; Mizutani, Manabu; Kan, Kazutoshi; Nozaki, Takayuki; Saitoh, Kazuo; Yamato, Masayuki; Okano, Teruo; Takeda, Shizu

2015-11-01

Automation technology for cell sheet-based tissue engineering would need to optimize the cell sheet fabrication process, stabilize cell sheet quality and reduce biological contamination risks. Biological contamination must be avoided in clinical settings. A closed culture system provides a solution for this. In the present study, we developed a closed culture device called a cell cartridge, to be used in a closed cell culture system for fabricating corneal epithelial cell sheets. Rabbit limbal epithelial cells were cultured on the surface of a porous membrane with 3T3 feeder cells, which are separate from the epithelial cells in the cell cartridges and in the cell-culture inserts as a control. To fabricate the stratified cell sheets, five different thicknesses of the membranes which were welded to the cell cartridge, were examined. Multilayered corneal epithelial cell sheets were fabricated in cell cartridges that were welded to a 25 µm-thick gas-permeable membrane, which was similar to the results with the cell-culture inserts. However, stratification of corneal epithelial cell sheets did not occur with cell cartridges that were welded to 100-300 µm-thick gas-permeable membranes. The fabricated cell sheets were evaluated by histological analyses to examine the expression of corneal epithelial-specific markers. Immunohistochemical analyses showed that a putative stem cell marker, p63, a corneal epithelial differentiation maker, CK3, and a barrier function marker, Claudin-1, were expressed in the appropriate position in the cell sheets. These results suggest that the cell cartridge is effective for fabricating corneal epithelial cell sheets. Copyright © 2012 John Wiley & Sons, Ltd.

A Cell Culture Approach to Optimized Human Corneal Endothelial Cell Function

PubMed Central

Bartakova, Alena; Kuzmenko, Olga; Alvarez-Delfin, Karen; Kunzevitzky, Noelia J.; Goldberg, Jeffrey L.

2018-01-01

Purpose Cell-based therapies to replace corneal endothelium depend on culture methods to optimize human corneal endothelial cell (HCEC) function and minimize endothelial-mesenchymal transition (EnMT). Here we explore contribution of low-mitogenic media on stabilization of phenotypes in vitro that mimic those of HCECs in vivo. Methods HCECs were isolated from cadaveric donor corneas and expanded in vitro, comparing continuous presence of exogenous growth factors (“proliferative media”) to media without those factors (“stabilizing media”). Identity based on canonical morphology and expression of surface marker CD56, and function based on formation of tight junction barriers measured by trans-endothelial electrical resistance assays (TEER) were assessed. Results Primary HCECs cultured in proliferative media underwent EnMT after three to four passages, becoming increasingly fibroblastic. Stabilizing the cells before each passage by switching them to a media low in mitogenic growth factors and serum preserved canonical morphology and yielded a higher number of cells. HCECs cultured in stabilizing media increased both expression of the identity marker CD56 and also tight junction monolayer integrity compared to cells cultured without stabilization. Conclusions HCECs isolated from donor corneas and expanded in vitro with a low-mitogenic media stabilizing step before each passage demonstrate more canonical structural and functional features and defer EnMT, increasing the number of passages and total canonical cell yield. This approach may facilitate development of HCEC-based cell therapies. PMID:29625488

Mechanism of transcorneal permeation of pilocarpine.

PubMed

Mitra, A K; Mikkelson, T J

1988-09-01

The mechanism of transcorneal permeation of pilocarpine has been investigated in relation to the physicochemical properties of the permeating species and its interaction with the membrane biophase. In vitro corneal transport experiments suggested the transport of un-ionized as well as ionized pilocarpine species across the corneal membrane. However, the permeability of the ionized pilocarpine species was 4.818 x 10(-6) cm s-1, a value only one-half of that obtained for the un-ionized pilocarpine species (9.744 x 10(-6) cm s-1). Further evidence of ion transport across the cornea was obtained by examining the transport of the quaternized pilocarpine compound (i.e., pilocarpinium methyl iodide). The quaternized compound had a corneal permeability of 4.66 x 10(-6) cm s-1, similar to that obtained for the ionized pilocarpine species. The lipoidal epithelial layer of the corneal membrane appears to be the predominant barrier to the transport of polar species. Therefore, the transport of pilocarpinium cations across the lipoidal epithelium might have occurred as tightly bound ion pairs with dihydrogen phosphate and/or nitrate counter ions. Excellent linear correlation has been obtained between pilocarpine corneal permeability and the 1-octanol-water partition coefficient as a function of the state of ionization of pilocarpine. The ratio of un-ionized to ionized drug permeability across the cornea is expected to be much higher for drugs with higher 1-octanol-water partition coefficients.

The Corneal Epithelial Barrier and Its Developmental Role in Isolating Corneal Epithelial and Conjunctival Cells From One Another

PubMed Central

Kubilus, James K.; Zapater i Morales, Carolina; Linsenmayer, Thomas F.

2017-01-01

Purpose During development, the corneal epithelium (CE) and the conjunctiva are derived from the surface ectoderm. Here we have examined how, during development, the cells of these two issues become isolated from each other. Methods Epithelia from the anterior eyes of chicken embryos were labeled with the fluorescent, lipophilic dye, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI). DiI was placed on the epithelial surface of the developing anterior eye and its diffusion was monitored by fluorescence microscopy. Concomitant morphologic changes in the surface cells of these epithelial were examined by scanning electron microscopy. Immunofluorescence was used to analyze the expression of cytokeratin K3, ZO-1, N-cadherin and Connexin-43 and the function of gap junctions was analyzed using a cut-loading with the fluorescent dye rhodamine-dextran. Results Prior to embryonic day 8 (E8), DiI placed on the surface of the CE spreads throughout all the epithelial cells of the anterior eye. When older eyes were similarly labeled, dye diffusion was restricted to the CE. Similarly, diffusion of DiI placed on the conjunctival surface after E8 was restricted to the conjunctiva. Scanning electron microscopy showed that developmentally (1) physical separations progressively form between the cells of the CE and those of the conjunctiva, and (2) by E8 these separations form a ring that completely encompasses the cornea. The functional restriction of gap junctions between these tissues did not occur until E14. Conclusions During ocular development, a barrier to the diffusion of DiI forms between the contiguous CE and conjunctiva prior to the differential expression of gap junctions within these tissues. PMID:28319640

Attitudes and Perception Towards Eye Donation in Patients with Corneal Disease: A Case-controlled Population-based Study.

PubMed

Noopur, Gupta; Praveen, Vashist; Radhika, Tandon; Sanjeev K, Gupta; Mani, Kalaivani; Deepak, Kumar

2018-06-01

To assess awareness, barriers, and misconceptions related to eye donation in people with corneal disease as compared to controls in a population setting. A population-based study was conducted in 25 randomly selected clusters of Rural Gurgaon, Haryana, India, as part of the CORE (Cornea Opacity Rural Epidemiological) study. In addition to ophthalmic examination, knowledge and perceptions regarding eye donation were assessed through a validated questionnaire. The questionnaire captured the sociodemographic factors influencing awareness regarding eye donation in participants with corneal disease and twice the number of age- and gender-matched controls recruited from the same study clusters. Descriptive statistics were computed along with multivariable logistic regression analysis to determine associated factors for awareness of eye donation. In the CORE study, 452 participants had corneal opacities on ocular examination. Of these, 442 were assessed for eye donation awareness. Additionally, 884 age- and gender-matched controls were recruited. The mean age of cases and controls was 60.9 ± 15.5 and 59.6 ± 14.3 years, respectively. Awareness of eye donation in cases and controls was 46.4% (n = 205 of 442) and 52.3% (n = 462 of 884), respectively (P = 0.044). Educational status was an important factor determining knowledge about eye donation in both cases and controls (P = < 0.001). Major barriers reported for not pledging eyes were lack of willingness (36.7%) and ignorance (15.3%). Common misconceptions like eyes could be donated before death or even after 24 h of death and that any type of blindness could be treated with corneal transplantation were prevalent. The study demonstrated that although there is substantial awareness about eye donation, there are numerous barriers in this population that need to be resolved to improve donation rates. Additional efforts are needed to translate this awareness into actual eye donation in both cases with corneal disease and controls.

Inflammation in dry eye.

PubMed

Stern, Michael E; Pflugfelder, Stephen C

2004-04-01

Dry eye is a condition of altered tear composition that results from a diseased or dysfunctional lacrimal functional unit. Evidence suggests that inflammation causes structural alterations and/or functional paralysis of the tear-secreting glands. Changes in tear composition resulting from lacrimal dysfunction, increased evaporation and/or poor clearance have pro-inflammatory effects on the ocular surface. This inflammation is responsible in part for the irritation symptoms, ocular surface epithelial disease, and altered corneal epithelial barrier function in dry eye. Anti-inflammatory therapies for dry eye target one or more of the inflammatory mediators/pathways that have been identified in dry eye.

Sjögren's syndrome associated dry eye in a mouse model is ameliorated by topical application of integrin α4 antagonist GW559090.

PubMed

Contreras-Ruiz, Laura; Mir, Fayaz A; Turpie, Bruce; Krauss, Achim H; Masli, Sharmila

2016-02-01

Sjögren's syndrome is an autoimmune disease associated with inflammation of exocrine glands with clinical manifestations of dry eye and dry mouth. Dry eye in this disease involves inflammation of the ocular surface tissues - cornea and conjunctiva. While systemic blockade of adhesion molecules has been used to treat autoimmune diseases, the purpose of this study was to determine the therapeutic efficacy of topical application of an integrin α4 adhesion molecule antagonist in a mouse model of dry eye associated with Sjögren's syndrome. To assess this spontaneously developed ocular surface inflammation related to Sjögren's syndrome in TSP-1null mice (12 wks) was evaluated. Mice were treated with topical formulations containing 0.1% dexamethasone or 30 mg/ml GW559090 or vehicle control. Corneal fluorescein staining and conjunctival goblet cell density were assessed. Real-time PCR analysis was performed to assess expression of the inflammatory marker IL-1β in the cornea and Tbet and RORγt in the draining lymph nodes. Ocular surface inflammation was detectable in TSP-1null mice (≥12 wk old), which resulted in increased corneal fluorescein staining indicative of corneal barrier disruption and reduced conjunctival goblet cell density. These changes were accompanied by increased corneal expression of IL-1β as compared to WT controls and an altered balance of Th1 (Tbet) and Th17 (RORγt) markers in the draining lymph nodes. Topically applied dexamethasone and GW559090 significantly reduced corneal fluorescein staining compared to vehicle treatment (p = 0.023 and p < 0.001, respectively). This improved corneal barrier integrity upon adhesion molecule blockade was consistent with significantly reduced corneal expression of pro-inflammatory IL-1β compared to vehicle treated groups (p < 0.05 for both treatments). Significant improvement in goblet cell density was also noted in mice treated with 0.1% dexamethasone and GW559090 (p < 0.05 for both). We conclude that similar to topical dexamethasone, topically administered GW559090 successfully improved corneal barrier integrity and inflammation in an established ocular surface disease associated with Sjögren's syndrome. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular evidence and functional expression of multidrug resistance associated protein (MRP) in rabbit corneal epithelial cells.

PubMed

Karla, Pradeep K; Pal, Dananjay; Mitra, Ashim K

2007-01-01

Multidrug resistance associated protein (MRP) is a major family of efflux transporters involved in drug efflux leading to drug resistance. The objective of this study was to explore physical barriers for ocular drug absorption and to verify if the role of efflux transporters. MRP-2 is a major homologue of MRP family and found to express on the apical side of cell membrane. Cultured Rabbit Corneal Epithelial Cells (rCEC) were selected as an in vitro model for corneal epithelium. [14C]-erythromycin which is a proven substrate for MRP-2 was selected as a model drug for functional expression studies. MK-571, a known specific and potent inhibitor for MRP-2 was added to inhibit MRP mediated efflux. Membrane fraction of rCEC was used for western blot analysis. Polarized transport of [14C]-erythromycin was observed in rCEC and transport from B-->A was significantly high than from A-->B. Permeability's increased significantly from A-->B in the presence of MK-571 and ketoconozole. Uptake of [14C]-erythromycin in the presence of MK-571 was significantly higher than control in rCEC. RT-PCR analysis indicated a unique and distinct band at approximately 498 bp corresponding to MRP-2 in rCEC and MDCK11-MRP-2 cells. Immunoprecipitation followed by Western Blot analysis indicated a specific band at approximately 190 kDa in membrane fraction of rCEC and MDCK11-MRP-2 cells. For the first time we have demonstrated high expression of MRP-2 in rabbit corneal epithelium and its functional activity causing drug efflux. RT-PCR, immunoprecipitation followed by Western blot analysis further confirms the result.

The Sokoto Blind Beggars: Causes of Blindness and Barriers to Rehabilitation Services

PubMed Central

Balarabe, Aliyu Hamza; Mahmoud, Abdulraheem O.; Ayanniyi, Abdulkabir Ayansiji

2014-01-01

Purpose: To determine the causes of blindness and the barriers to accessing rehabilitation services (RS) among blind street beggars (bsb) in Sokoto, Nigeria. Materials and Methods: A cross-sectional survey of 202 bsb (VA < 3/60) using interviewer administered questionnaire. The causes of blindness were diagnosed by clinical ophthalmic examination. Results: There were 107 (53%) males and 95 (47%) females with a mean age of 49 years (SD 12.2). Most bsb 191 (94.6%) had non-formal education. Of 190 (94.1%) irreversibly bsb, 180/190 (94.7%) had no light perception (NPL) bilaterally. The major causes of blindness were non-trachomatous corneal opacity (60.8%) and trachoma corneal opacity (12.8%). There were 166 (82%) blind from avoidable causes and 190 (94.1%) were irreversibly blind with 76.1% due to avoidable causes. The available sub-standard RS were educational, vocational and financial support. The barriers to RS in the past included non-availability 151 (87.8%), inability to afford 2 (1.2%), unfelt need 4 (2.3%), family refusal 1 (0.6), ignorance 6 (3.5%) and being not linked 8 (4.7%). The barriers to RS during the study period included inability of 72 subjects (35.6%) to access RS and 59 (81.9%) were due to lack of linkage to the existing services. Conclusion: Corneal opacification was the major cause of blindness among bsb. The main challenges to RS include the inadequate services available, societal and users factors. Renewed efforts are warranted toward the prevention of avoidable causes of blindness especially corneal opacities. The quality of life of the blind street beggar should be improved through available, accessible and affordable well-maintained and sustained rehabilitation services. PMID:24791106

The Sokoto blind beggars: causes of blindness and barriers to rehabilitation services.

PubMed

Balarabe, Aliyu Hamza; Mahmoud, Abdulraheem O; Ayanniyi, Abdulkabir Ayansiji

2014-01-01

To determine the causes of blindness and the barriers to accessing rehabilitation services (RS) among blind street beggars (bsb) in Sokoto, Nigeria. A cross-sectional survey of 202 bsb (VA < 3/60) using interviewer administered questionnaire. The causes of blindness were diagnosed by clinical ophthalmic examination. There were 107 (53%) males and 95 (47%) females with a mean age of 49 years (SD 12.2). Most bsb 191 (94.6%) had non-formal education. Of 190 (94.1%) irreversibly bsb, 180/190 (94.7%) had no light perception (NPL) bilaterally. The major causes of blindness were non-trachomatous corneal opacity (60.8%) and trachoma corneal opacity (12.8%). There were 166 (82%) blind from avoidable causes and 190 (94.1%) were irreversibly blind with 76.1% due to avoidable causes. The available sub-standard RS were educational, vocational and financial support. The barriers to RS in the past included non-availability 151 (87.8%), inability to afford 2 (1.2%), unfelt need 4 (2.3%), family refusal 1 (0.6), ignorance 6 (3.5%) and being not linked 8 (4.7%). The barriers to RS during the study period included inability of 72 subjects (35.6%) to access RS and 59 (81.9%) were due to lack of linkage to the existing services. Corneal opacification was the major cause of blindness among bsb. The main challenges to RS include the inadequate services available, societal and users factors. Renewed efforts are warranted toward the prevention of avoidable causes of blindness especially corneal opacities. The quality of life of the blind street beggar should be improved through available, accessible and affordable well-maintained and sustained rehabilitation services.

In vitro cell culture models to study the corneal drug absorption.

PubMed

Reichl, Stephan; Kölln, Christian; Hahne, Matthias; Verstraelen, Jessica

2011-05-01

Many diseases of the anterior eye segment are treated using topically applied ophthalmic drugs. For these drugs, the cornea is the main barrier to reaching the interior of the eye. In vitro studies regarding transcorneal drug absorption are commonly performed using excised corneas from experimental animals. Due to several disadvantages and limitations of these animal experiments, establishing corneal cell culture models has been attempted as an alternative. This review summarizes the development of in vitro models based on corneal cell cultures for permeation studies during the last 20 years, starting with simple epithelial models and moving toward complex organotypical 3D corneal equivalents. Current human 3D corneal cell culture models have the potential to replace excised animal corneas in drug absorption studies. However, for widespread use, the contemporary validation of existent systems is required.

[The cornea: stasis and dynamics].

PubMed

Nishida, Teruo

2008-03-01

The physiological roles of the cornea are to conduct external light into the eye, focus it, together with the lens, onto the retina, and to provide rigidity to the entire eyeball. Good vision thus requires maintenance of the transparency and proper refractive shape of the cornea. Although the cornea appears to be a relatively static structure, dynamic processes operate within and around the cornea at the tissue, cell, and molecular level. In this article, I review the mechanisms responsible for maintenance of corneal homeostasis as well as the development of new modes of treatment for various corneal diseases. I. The static cornea: structure and physiological functions. The cornea is derived from ectoderm, so that it can be considered as transparent skin. It is devoid of blood vessels and manifests the highest sensitivity in the entire body. The surface of the cornea is covered by tear fluid, which serves both as a lubricant and as a conduit for regulatory molecules. The cornea is also supplied with oxygen and various nutrients by the aqueous humor and a loop vascular system in addition to tear fluid. The cornea interacts with its surrounding tissues directly as well as indirectly through tear fluid or aqueous humor, with such interactions playing an important role in the regulation of corneal structure and functions. The resident cells of the cornea-epithelial cells, fibroblasts (keratocytes), and endothelial cells--also engage in mutual interactions through network systems. These interactions as well as those with infiltrated cells and regulation by nerves contribute to the maintenance of the normal structure and functions of the cornea as well as to the repair of corneal injuries. II. The dynamic cornea: maintenance of structure and functions by network systems. Developments in laser and computer technology have allowed observation of the cells and collagen fibers within the cornea. Furthermore, progress in cell and molecular biology has allowed characterization of dynamic network systems-including cell-cell and cell-extracellular matrix interactions as well as cytokines and neural factors-that contribute to the maintenance of corneal transparency and shape. III. Disruption of network systems: persistent corneal epithelial defects and corneal ulcer. Selection of the appropriate treatment for pathologic lesions of the cornea and the accompanying decrease in visual acuity requires localization of the lesion with regard to the epithelium, stroma, or endothelium of the cornea. In certain instances, however, it is not possible to determine the cause of the problem within the cornea. In such cases, the cause of the pathologic lesion and the target for treatment may lie in the surrounding tissues or environment. For example, corneal epithelial wound healing may be delayed, leading to the development of persistent epithelial defects, as a result of disruption of intercellular junctions between epithelial cells, an abnormality of the corneal basement membrane, altered concentrations of various cytokines in tear fluid, a lowered corneal sensation, or allergic reactions in the lid conjunctiva. Loss of corneal epithelial barrier function can further allow inflammatory cytokines present in tear fluid, together with infiltrated cells, to activate keratocytes and elicit excessive degradation of collagen in the stroma, thereby giving rise to corneal ulcer. IV. Development of new drugs for corneal diseases. We have attempted to apply the results of basic scientific research to the development of new drugs for corneal diseases that remain difficult to treat. The process of authorization for new drugs from the Ministry of Health, Labor, and Welfare takes more than two decades, however. The path from the bench to clinical practice is thus a long one. 1. Development of eyedrops for treatment of persistent corneal epithelial defects. We demonstrated the clinical efficacy of fibronectin eyedrops for the treatment of persistent epithelial defects of the cornea. However, the possibility of blood-borne infections has interfered with the development of serum-derived fibronectin as a drug. An automated machine for the preparation of autologous fibronectin eyedrops has therefore recently been developed. Furthermore, in seeking an alternative to fibronectin eyedrops, we are investigating the effects of a peptide corresponding to the second cell-binding domain of fibronectin on corneal epithelial wound healing. Considering that urokinase-type plasminogen activator may be expressed at the site of corneal epithelial defects and facilitates epithelial migration, the potential clinical application of annexin V, which stimulates the secretion of urokinase-type plasminogen activator for the treatment of persistent corneal epithelial defects is also now under investigation in Japan. 2. Development of eyedrops for treatment of neurotrophic keratopathy. Substance P, a neurotransmitter, stimulates corneal epithelial migration in a synergistic manner with insulin-like growth factor (IGF)--1. We have shown that eyedrops containing both the substance P-derived peptide FGLM-amide and the IGF-1--derived peptide SSSR are effective for the treatment of persistent corneal epithelial defects in individuals with diabetic keratopathy or neurotrophic keratopathy, both of which are associated with a reduction in corneal sensation. 3. Development of drugs for corneal ulcer. Treatment of corneal infection with antibiotics does not necessarily halt the process of corneal ulceration, which is characterized by excessive degradation of stromal collagen, or resolve persistent corneal epithelial defects. In addition to eyedrops for the treatment of persistent corneal epithelial defects, we have therefore also been working on the development of new drugs for the treatment of corneal ulcer. To this end, we have established an experimental system in which corneal fibroblasts are cultured in a three-dimensional collagen gel. With this system, we have shown that triptolide and steroids inhibit collagen degradation by corneal fibroblasts. Triptolide or its derivatives are thus potential drugs for the treatment of corneal ulcer and would work by acting directly on corneal fibroblasts rather than by inhibiting the secreted enzymes(matrix metalloproteinases) responsible for collagen degradation.

Long-term follow-up after submandibular gland transplantation in severe dry eyes secondary to cicatrizing conjunctivitis.

PubMed

Borrelli, Maria; Schröder, Christina; Dart, John K G; Collin, John Richard O; Sieg, Peter; Cree, Ian A; Matheson, Melville A; Tiffany, John M; Proctor, Gordon; van Best, Jaap; Hyde, Nick; Geerling, Gerd

2010-12-01

To evaluate the long-term results of autologous submandibular gland transplantation in eyes with cicatrizing conjunctivitis and to determine biomechanical and biochemical features of the resulting salivary tear film. Prospective, observational case series. Fifteen eyes with cicatrizing conjunctivitis with a viable autologous submandibular gland transplantation were compared with 10 eyes with cicatrizing conjunctivitis and a failed submandibular gland transplantation or no submandibular gland transplantation. Best-corrected visual acuity, frequency of tear substitute instillation, severity of dry eye discomfort, lid margin erythema, conjunctival hyperemia, corneal epithelial edema, tear film break-up time, Schirmer test results, and corneal fluorescein and conjunctival Rose Bengal staining were evaluated. In a subgroup central corneal thickness and sensitivity, corneal epithelial barrier function, conjunctival and lid margin flora, and conjunctival impression cytologic analysis results were evaluated. In 3 patients, preoperative and postoperative tear samples were analyzed for viscosity, surface tension, and presence of mucins. Submandibular gland autotransplantation resulted in long-term improvement of subjective, objective, and some ocular surface parameters. Salivary mucins were detectable in salivary tears after submandibular gland transplantation. The viscosity of salivary tears was more similar to normal saliva and the surface tension was intermediate between the 2 original secretions. Submandibular gland autotransplantation provides long-term relief from pain and reduces the need for frequent installation of lubricants. Copyright © 2010 Elsevier Inc. All rights reserved.

Corneal Power Distribution and Functional Optical Zone Following Small Incision Lenticule Extraction for Myopia.

PubMed

Qian, Yishan; Huang, Jia; Zhou, Xingtao; Hanna, Rewais Benjamin

2015-08-01

To evaluate corneal power distribution using the ray tracing method (corneal power) in eyes undergoing small incision lenticule extraction (SMILE) surgery and compare the functional optical zone with two lenticular sizes. This retrospective study evaluated 128 patients who underwent SMILE for the correction of myopia and astigmatism with a lenticular diameter of 6.5 mm (the 6.5-mm group) and 6.2 mm (the 6.2-mm group). The data include refraction, correction, and corneal power obtained via a Scheimpflug camera from the pupil center to 8 mm. The surgically induced changes in corneal power (Δcorneal power) were compared to correction and Δrefraction. The functional optical zone was defined as the largest ring diameter when the difference between the ring power and the pupil center power was 1.50 diopters or less. The functional optical zone was compared between two lenticular diameter groups. Corneal power distribution was measured by the ray tracing method. In the 6.5-mm group (n=100), Δcorneal power at 5 mm showed the smallest difference from Δrefraction and Δcorneal power at 0 mm exhibited the smallest difference from correction. In the 6.2-mm group (n=28), Δcorneal power at 2 mm displayed the lowest dissimilarity from Δrefraction and Δcorneal power at 4 mm demonstrated the lowest dissimilarity from correction. There was no significant difference between the mean postoperative functional optical zones in either group when their spherical equivalents were matched. Total corneal refactive power can be used in the evaluation of surgically induced changes following SMILE. A lenticular diameter of 6.2 mm should be recommended for patients with high myopia because there is no functional difference in the optical zone. Copyright 2015, SLACK Incorporated.

Quercetin and the ocular surface: What we know and where we are going

PubMed Central

McKay, Tina B

2017-01-01

Flavonoids are a class of plant and fungus secondary metabolites that serve functional roles in protecting against UV-induced oxidative stress, mediating auxin signaling, and promoting microbial defense. Flavonoids are extremely abundant in nature where their potent antioxidant capacity and very low toxicity makes them highly attractive as potential therapeutic agents. In terms of clinical applications, neither the Food and Drug Administration (FDA) nor the European Food Safety Authority (EFSA) has approved any health claims or drugs related to the use of flavonoids for therapeutic purposes. Quercetin is a common flavonol that has been shown to have potent antioxidant, anti-inflammatory, and anti-fibrotic activities both in vitro and in vivo in various tissues. Recently, the application of quercetin as a therapeutic has been gaining attention in the ocular surface scientific community in the study of dry eye, keratoconus, inflammation, and neovascularization of the cornea. This review will discuss the latest findings and the use of quercetin for the treatment of dystrophies of the ocular surface. Impact statement The eye represents a small portion of the human body, accounting for one decimal fraction of the anterior body surface. The cornea is an avascular, transparent tissue that acts as a primary barrier against mechanical and infectious damaging agents, protecting the internal structures of the eye. Corneal survival and function are affected by a number of factors including but not limited to injury, trauma, infection, genetics, and environment. Corneal injury, or trauma, often leads to loss of corneal transparency and even blindness. The concept of “curing” corneal opacity has been discussed in published form for over 200 years. Currently, full corneal transplant is the only treatment option. There is a strong interest in developing natural therapeutic products that come with minimum side effects. A novel antioxidant flavonoid, quercetin, has been gaining traction as a potential therapeutic to prevent the injured cornea. This review discusses the potential of this antioxidant. PMID:28056553

Quercetin and the ocular surface: What we know and where we are going.

PubMed

McKay, Tina B; Karamichos, Dimitrios

2017-03-01

Flavonoids are a class of plant and fungus secondary metabolites that serve functional roles in protecting against UV-induced oxidative stress, mediating auxin signaling, and promoting microbial defense. Flavonoids are extremely abundant in nature where their potent antioxidant capacity and very low toxicity makes them highly attractive as potential therapeutic agents. In terms of clinical applications, neither the Food and Drug Administration (FDA) nor the European Food Safety Authority (EFSA) has approved any health claims or drugs related to the use of flavonoids for therapeutic purposes. Quercetin is a common flavonol that has been shown to have potent antioxidant, anti-inflammatory, and anti-fibrotic activities both in vitro and in vivo in various tissues. Recently, the application of quercetin as a therapeutic has been gaining attention in the ocular surface scientific community in the study of dry eye, keratoconus, inflammation, and neovascularization of the cornea. This review will discuss the latest findings and the use of quercetin for the treatment of dystrophies of the ocular surface. Impact statement The eye represents a small portion of the human body, accounting for one decimal fraction of the anterior body surface. The cornea is an avascular, transparent tissue that acts as a primary barrier against mechanical and infectious damaging agents, protecting the internal structures of the eye. Corneal survival and function are affected by a number of factors including but not limited to injury, trauma, infection, genetics, and environment. Corneal injury, or trauma, often leads to loss of corneal transparency and even blindness. The concept of "curing" corneal opacity has been discussed in published form for over 200 years. Currently, full corneal transplant is the only treatment option. There is a strong interest in developing natural therapeutic products that come with minimum side effects. A novel antioxidant flavonoid, quercetin, has been gaining traction as a potential therapeutic to prevent the injured cornea. This review discusses the potential of this antioxidant.

Nonclinical safety evaluation of boric acid and a novel borate-buffered contact lens multi-purpose solution, Biotrue™ multi-purpose solution.

PubMed

Lehmann, David M; Cavet, Megan E; Richardson, Mary E

2010-12-01

Multipurpose solutions (MPS) often contain low concentrations of boric acid as a buffering agent. Limited published literature has suggested that boric acid and borate-buffered MPS may alter the corneal epithelium; an effect attributed to cytotoxicity induced by boric acid. However, this claim has not been substantiated. We investigated the effect of treating cells with relevant concentrations of boric acid using two cytotoxicity assays, and also assessed the impact of boric acid on corneal epithelial barrier function by measuring TEER and immunostaining for tight junction protein ZO-1 in human corneal epithelial cells. Boric acid was also assessed in an in vivo ocular model when administered for 28 days. Additionally, we evaluated Biotrue multi-purpose solution, a novel borate-buffered MPS, alone and with contact lenses for ocular compatibility in vitro and in vivo. Boric acid passed both cytotoxicity assays and did not alter ZO-1 distribution or corneal TEER. Furthermore, boric acid was well-tolerated on-eye following repeated administration in a rabbit model. Finally, Biotrue multi-purpose solution demonstrated good ocular biocompatibility both in vitro and in vivo. This MPS was not cytotoxic and was compatible with the eye when administered alone and when evaluated with contact lenses. We demonstrate that boric acid and a borate-buffered MPS is compatible with the ocular environment. Our findings provide evidence that ocular effects reported for some borate-buffered MPS may be incorrectly attributed to boric acid and are more likely a function of the unique combination of ingredients in the MPS formulation tested. Copyright © 2010 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Up-regulation of the tight-junction protein ZO-1 by substance P and IGF-1 in A431 cells.

PubMed

Ko, Ji-Ae; Murata, Shizuka; Nishida, Teruo

2009-08-01

The formation of a barrier by tight junctions is important in epithelia of various tissues. Substance P (SP) and insulin-like growth factor (IGF)-1 synergistically promote barrier function in the corneal epithelium. We have now examined the effects of SP and IGF-1 on expression of the tight-junction protein zonula occludens (ZO)-1 in A431 human epidermoid carcinoma cells. Reverse transcription-polymerase chain reaction (RT-PCR) and immunoblot analyses revealed that SP and IGF-1 increased the amounts of ZO-1 mRNA and protein in these cells in a concentration-dependent manner, with neither SP nor IGF-1 alone having such an effect. The SP- and IGF-1-induced up-regulation of ZO-1 was accompanied by phosphorylation of extracellular signal-regulated kinase (ERK), and both of these effects were blocked by PD98059, an inhibitor of ERK activation. SP and IGF-1 also increased the transepithelial electrical resistance (TER) (an indicator of barrier function) of an A431 cell monolayer in a manner sensitive to PD98059. Our results thus suggest that the synergistic induction of ZO-1 expression by SP and IGF-1 may promote barrier function in skin epithelial cells. (c) 2009 John Wiley & Sons, Ltd.

Tissue Engineering of the Corneal Endothelium: A Review of Carrier Materials

PubMed Central

Teichmann, Juliane; Valtink, Monika; Nitschke, Mirko; Gramm, Stefan; Funk, Richard H.W.; Engelmann, Katrin; Werner, Carsten

2013-01-01

Functional impairment of the human corneal endothelium can lead to corneal blindness. In order to meet the high demand for transplants with an appropriate human corneal endothelial cell density as a prerequisite for corneal function, several tissue engineering techniques have been developed to generate transplantable endothelial cell sheets. These approaches range from the use of natural membranes, biological polymers and biosynthetic material compositions, to completely synthetic materials as matrices for corneal endothelial cell sheet generation. This review gives an overview about currently used materials for the generation of transplantable corneal endothelial cell sheets with a special focus on thermo-responsive polymer coatings. PMID:24956190

EMMPRIN Modulates Epithelial Barrier Function through a MMP–Mediated Occludin Cleavage

PubMed Central

Huet, Eric; Vallée, Benoit; Delbé, Jean; Mourah, Samia; Prulière-Escabasse, Virginie; Tremouilleres, Magali; Kadomatsu, Kenji; Doan, Serge; Baudouin, Christophe; Menashi, Suzanne; Gabison, Eric E.

2011-01-01

Dry eye is a common disease that develops as a result of alteration of tear fluid, leading to osmotic stress and a perturbed epithelial barrier. Matrix metalloproteinase-9 (MMP-9) may be important in dry eye disease, as its genetic knockout conferred resistance to the epithelial disruption. We show that extracellular matrix metalloproteinase inducer (EMMPRIN; also termed CD147), an inducer of MMP expression, participates in the pathogenesis of dry eye through MMP-mediated cleavage of occludin, an important component of tight junctions. EMMPRIN expression was increased on the ocular surface of dry eye patients and correlated with those of MMP-9. High osmolarity in cell culture, mimicking dry eye conditions, increased both EMMPRIN and MMP-9 and resulted in the disruption of epithelial junctions through the cleavage of occludin. Exogenously added recombinant EMMPRIN had similar effects that were abrogated in the presence of the MMP inhibitor marimastat. Membrane occludin immunostaining was markedly increased in the apical corneal epithelium of both EMMPRIN and MMP-9 knock-out mice. Furthermore, an inverse correlation between EMMPRIN and occludin membrane staining was consistently observed both in vitro and in vivo as a function of corneal epithelial cells differentiation. These data suggest a possible role of EMMPRIN in regulating the amount of occludin at the cell surface in homeostasis beyond pathological situations such as dry eye disease, and EMMPRIN may be essential for the formation and maintenance of organized epithelial structure. PMID:21777561

Rationale for anti-inflammatory therapy in dry eye syndrome.

PubMed

de Paiva, C S; Pflugfelder, S C

2008-01-01

Dry eye is a multifactorial condition that results in a dysfunctional lacrimal functional unit. Evidence suggests that inflammation is involved in the pathogenesis of the disease. Changes in tear composition including increased cytokines, chemokines, metalloproteinases and the number of T cells in the conjunctiva are found in dry eye patients and in animal models. This inflammation is responsible in part for the irritation symptoms, ocular surface epithelial disease, and altered corneal epithelial barrier function in dry eye. There are several anti-inflammatory therapies for dry eye that target one or more of the inflammatory mediators/pathways that have been identified and are discussed in detail.

Gene Therapy in the Cornea: 2005-present

PubMed Central

Mohan, Rajiv R.; Tovey, Jonathan C.K.; Sharma, Ajay; Tandon, Ashish

2011-01-01

Successful restoration of vision in human patients with gene therapy affirmed its promise to cure ocular diseases and disorders. The efficacy of gene therapy is contingent upon vector and mode of therapeutic DNA introduction into targeted cells/tissues. The cornea is an ideal tissue for gene therapy due to its ease of access and relative immune-privilege. Considerable progress has been made in the field of corneal gene therapy in last 5 years. Several new gene transfer vectors, techniques and approaches have evolved. Although corneal gene therapy is still in its early stages of development, the potential of gene-based interventions to treat corneal abnormalities have begun to surface. Identification of next generation viral and nanoparticle vectors, characterization of delivered gene levels, localization, and duration in the cornea, and significant success in controlling corneal disorders, particularly fibrosis and angiogenesis, in experimental animal disease models, with no major side effects have propelled gene therapy a step closer towards establishing gene-based therapies for corneal blindness. Recently, researchers have assessed the delivery of therapeutic genes for corneal diseases and disorders due to trauma, infections, chemical, mechanical, and surgical injury, and/or abnormal wound healing. This review provides an update on the developments in gene therapy for corneal diseases and discusses the barriers that hinder its utilization for delivering genes in the cornea. PMID:21967960

Breakdown evaluation of corneal epithelial barrier caused by antiallergic eyedrops using an electrophysiologic method.

PubMed

Nakashima, Mikiro; Nakamura, Tadahiro; Teshima, Mugen; To, Hideto; Uematsu, Masafumi; Kitaoka, Takashi; Taniyama, Kotaro; Nishida, Koyo; Nakamura, Junzo; Sasaki, Hitoshi

2008-02-01

The aim of this study was to examine the usefulness of an electrophysiologic method for predicting corneal epithelial breakdown by antiallergic eyedrops and comparing the results with those in other appraisal methods. Six kinds of antiallergic eyedrops, including benzalkonium chloride (BK) as an ophthalmic preservative and two kinds of BK-free antiallergic eyedrops, were used in this study. Eyedrops were applied to excise rabbit corneas and monitoring was performed according to an electrophysiologic method, using a commercially available chamber system to mimic human tear turnover. Changes in transepithelial electrical resistance (TEER) in the corneal surface were recorded. The cytotoxicity of each kind of eyedrops in a normal rabbit corneal epithelial (NRCE) cell line and a human endothelial cell line EA.hy926 was also examined. The extent of decrease in the corneal TEER after applying antiallergic eyedrops was dependent on the concentration of the BK included as a preservative, but it was also affected by the different kinds of drugs when the BK concentration was low. Higher cytotoxicity of the eyedrops against the NRCE and EA.hy926 cell lines was observed with a reduction of TEER. Monitoring changes in the corneal TEER, according to the electrophysiologic method with the application of antiallergic eyedrops, is useful for predicting corneal epithelial breakdown caused by their instillation.

The corneal fibrosis response to epithelial-stromal injury

PubMed Central

Torricelli, Andre A. M.; Santhanam, Abirami; Wu, Jiahui; Singh, Vivek; Wilson, Steven E.

2014-01-01

The corneal wound healing response, including the development of stromal opacity in some eyes, is a process that often leads to scarring that occurs after injury, surgery or infection to the cornea. Immediately after epithelial and stromal injury, a complex sequence of processes contributes to wound repair and regeneration of normal corneal structure and function. In some corneas, however, often depending on the type and extent of injury, the response may also lead to the development of mature vimentin+ α-smooth muscle actin+ desmin+ myofibroblasts. Myofibroblasts are specialized fibroblastic cells generated in the cornea from keratocyte-derived or bone marrow-derived precursor cells. The disorganized extracellular matrix components secreted by myofibroblasts, in addition to decreased expression of corneal crystallins in these cells, are central biological processes that result in corneal stromal fibrosis associated with opacity or “haze”. Several factors are associated with myofibroblast generation and haze development after PRK surgery in rabbits, a reproducible model of scarring, including the amount of tissue ablated, which may relate to the extent of keratocyte apoptosis in the early response to injury, irregularity of stromal surface after surgery, and changes on corneal stromal proteoglycans, but normal regeneration of the epithelial basement membrane (EBM) appears to be a critical factor determining whether a cornea heals with relative transparency or vision-limiting stromal opacity. Structural and functional abnormalities of the regenerated EBM facilitate prolonged entry of epithelium-derived growth factors such as transforming growth factor β (TGF-β) and platelet-derived growth factor (PDGF) into the stroma that both drive development of mature myofibroblasts from precursor cells and lead to persistence of the cells in the anterior stroma. A major discovery that has contributed to our understanding of haze development is that keratocytes and corneal fibroblasts, but not myofibroblasts, produce large amounts of critical EBM components, such as nidogen-1, nidogen-2 and perlecan, that are essential for complete regeneration of a normal EBM once laminin secreted by epithelial cells self-polymerizes into a nascent EBM. Mature myofibroblasts that become established in the anterior stroma are a barrier to keratocyte contributions to the nascent EBM. These myofibroblasts, and the opacity they produce, often persist for months or years after the injury. Transparency is subsequently restored when the EBM is completely regenerated, myofibroblasts are deprived of TGFβ and undergo apoptosis, and the keratocytes re-occupy the anterior stroma and reabsorb disordered extracellular matrix. The aim of this review is to highlight factors involved in the generation of stromal haze and its subsequent removal. PMID:26675407

A new 3D reconstituted human corneal epithelium model as an alternative method for the eye irritation test.

PubMed

Jung, Kyoung-Mi; Lee, Su-Hyon; Ryu, Yang-Hwan; Jang, Won-Hee; Jung, Haeng-Sun; Han, Ju-Hee; Seok, Seung-Hyeok; Park, Jae-Hak; Son, Youngsook; Park, Young-Ho; Lim, Kyung-Min

2011-02-01

Many efforts are being made to develop new alternative in vitro test methods for the eye irritation test. Here we report a new reconstructed human corneal epithelial model (MCTT HCE model) prepared from primary-cultured human limbal epithelial cells as a new alternative in vitro eye irritation test method. In histological and immunohistochemical observation, MCTT HCE model displayed a morphology and biomarker expressions similar to intact human cornea. Moreover, the barrier function was well preserved as measured by high transepithelial electrical resistance, effective time-50 for Triton X-100, and corneal thickness. To employ the model as a new alternative method for eye irritation test, protocol refinement was performed and optimum assay condition was determined including treatment time, treatment volume, post-incubation time and rinsing method. Using the refined protocol, 25 reference chemicals with known eye irritation potentials were tested. With the viability cut-off value at 50%, chemicals were classified to irritant or non-irritant. When compared with GHS classification, the MCTT HCE model showed the accuracy of 88%, sensitivity of 100% and specificity of 77%. These results suggest that the MCTT HCE model might be useful as a new alternative eye irritation test method. Copyright © 2010 Elsevier Ltd. All rights reserved.

Ability of Mn2+ to Permeate the Eye and Availability of Manganese-enhanced Magnetic Resonance Imaging for Visual Pathway Imaging via Topical Administration

PubMed Central

Chen, Yao; Shi, Chun-Yan; Li, Ying; Hu, Yun-Tao; Han, Hong-Bin; Sun, Xiao-Dong; Salvi, Satyajeet S; Ma, Zhi-Zhong

2016-01-01

Background: Manganese-enhanced magnetic resonance imaging (MEMRI) for visual pathway imaging via topical administration requires further research. This study investigated the permeability of the corneal epithelium and corneal toxicity after topical administration of Mn2+ to understand the applicability of MEMRI. Methods: Forty New Zealand rabbits were divided into 0.05 mol/L, 0.10 mol/L, and 0.20 mol/L groups as well as a control group (n = 10 in each group). Each group was further subdivided into epithelium-removed and epithelium-intact subgroups (n = 5 in each subgroup). Rabbits were given 8 drops of MnCl2 in 5 min intervals. The Mn2+ concentrations in the aqueous and vitreous humors were analyzed using inductively coupled plasma-mass spectrometry at different time points. MEMRI scanning was carried out to image the visual pathway after 24 h. The corneal toxicity of Mn2+ was evaluated with corneal imaging and pathology slices. Results: Between the aqueous and vitreous humors, there was a 10 h lag for the peak Mn2+ concentration times. The intraocular Mn2+ concentration increased with the concentration gradients of Mn2+ and was higher in the epithelium-removed subgroup than that in the epithelium-intact subgroup. The enhancement of the visual pathway was achieved in the 0.10 mol/L and 0.20 mol/L epithelium-removed subgroups. The corresponding peak concentrations of Mn2+ were 5087 ± 666 ng/ml, 22920 ± 1188 ng/ml in the aqueous humor and 884 ± 78 ng/ml, 2556 ± 492 ng/ml in the vitreous body, respectively. Corneal injury was evident in the epithelium-removed and 0.20 mol/L epithelium-intact subgroups. Conclusions: The corneal epithelium is a barrier to Mn2+, and the iris and lens septum might be another intraocular barrier to the permeation of Mn2+. An elevated Mn2+ concentration contributes to the increased permeation of Mn2+, higher MEMRI signal, and corneal toxicity. The enhancement of the visual pathway requires an effective Mn2+ concentration in the vitreous body. PMID:27453232

EMMPRIN modulates epithelial barrier function through a MMP-mediated occludin cleavage: implications in dry eye disease.

PubMed

Huet, Eric; Vallée, Benoit; Delbé, Jean; Mourah, Samia; Prulière-Escabasse, Virginie; Tremouilleres, Magali; Kadomatsu, Kenji; Doan, Serge; Baudouin, Christophe; Menashi, Suzanne; Gabison, Eric E

2011-09-01

Dry eye is a common disease that develops as a result of alteration of tear fluid, leading to osmotic stress and a perturbed epithelial barrier. Matrix metalloproteinase-9 (MMP-9) may be important in dry eye disease, as its genetic knockout conferred resistance to the epithelial disruption. We show that extracellular matrix metalloproteinase inducer (EMMPRIN; also termed CD147), an inducer of MMP expression, participates in the pathogenesis of dry eye through MMP-mediated cleavage of occludin, an important component of tight junctions. EMMPRIN expression was increased on the ocular surface of dry eye patients and correlated with those of MMP-9. High osmolarity in cell culture, mimicking dry eye conditions, increased both EMMPRIN and MMP-9 and resulted in the disruption of epithelial junctions through the cleavage of occludin. Exogenously added recombinant EMMPRIN had similar effects that were abrogated in the presence of the MMP inhibitor marimastat. Membrane occludin immunostaining was markedly increased in the apical corneal epithelium of both EMMPRIN and MMP-9 knock-out mice. Furthermore, an inverse correlation between EMMPRIN and occludin membrane staining was consistently observed both in vitro and in vivo as a function of corneal epithelial cells differentiation. These data suggest a possible role of EMMPRIN in regulating the amount of occludin at the cell surface in homeostasis beyond pathological situations such as dry eye disease, and EMMPRIN may be essential for the formation and maintenance of organized epithelial structure. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Age-Related Changes in Corneal Astigmatism.

PubMed

Shao, Xu; Zhou, Kai-Jing; Pan, An-Peng; Cheng, Xue-Ying; Cai, He-Xie; Huang, Jin-Hai; Yu, A-Yong

2017-10-01

To analyze the changes in corneal astigmatism as a function of age and develop a novel model to estimate corneal astigmatic change according to age. This was a cross-sectional study of right eyes of 3,769 individuals. Total corneal astigmatism, keratometric astigmatism, anterior corneal astigmatism, and posterior corneal astigmatism were measured by a Scheimpflug tomographer. Smoothing fitting curves of polar values of corneal astigmatism as a function of age were drawn and average changes in corneal astigmatism at different ages were calculated. Two turning points of age on total corneal astigmatism were 36 and 69 years. The average change of total corneal astigmatism toward against-the-rule astigmatism was 0.13 diopters (D)/10 years from 18 to 35 years, 0.45 D/10 years from 36 to 68 years, and decreased after 69 years, mainly caused by anterior corneal astigmatism. The mean magnitude of posterior corneal astigmatism was -0.33 D and exceeded 0.50 D in 14.27% of eyes. The vectorial difference between total corneal astigmatism and keratometric astigmatism was correlated with posterior corneal astigmatism, polar value of anterior corneal astigmatism, age, and corneal higher order aberrations (r = 0.636; standard partial regression coefficients were 0.479, -0.466, 0.282, and 0.196, respectively; all P < .001). Based on the non-linear model to estimate corneal astigmatic change with age, a formula was developed to calculate recommended correction of astigmatism according to age and astigmatic type. The rate of change of total corneal astigmatism showed a non-linear trend toward against-the-rule astigmatism, which was low at young and old age, high at middle age, and should be taken into account when performing surgery to correct astigmatism. [J Refract Surg. 2017;33(10):696-703.]. Copyright 2017, SLACK Incorporated.

Managing Sjögren's Syndrome and non-Sjögren Syndrome dry eye with anti-inflammatory therapy.

PubMed

Coursey, Terry G; de Paiva, Cintia S

2014-01-01

Dry eye from Sjögren's syndrome is a multifactorial disease that results in dysfunction of the lacrimal functional unit. Studies have shown changes in tear composition, including inflammatory cytokines, chemokines, and metalloproteinase. T-lymphocytes have been shown to increase in the conjunctiva and lacrimal glands in patient and animal models. This inflammation is in part responsible for the pathogenesis of the disease, which results in symptoms of eye irritation, ocular surface epithelial disease, and loss of corneal barrier function. There are a number of anti-inflammatory approaches for treating this disease. The current study reviews details of immune response and anti-inflammatory therapies used to control this disease.

Modeling corneal surfaces with rational functions for high-speed videokeratoscopy data compression.

PubMed

Schneider, Martin; Iskander, D Robert; Collins, Michael J

2009-02-01

High-speed videokeratoscopy is an emerging technique that enables study of the corneal surface and tear-film dynamics. Unlike its static predecessor, this new technique results in a very large amount of digital data for which storage needs become significant. We aimed to design a compression technique that would use mathematical functions to parsimoniously fit corneal surface data with a minimum number of coefficients. Since the Zernike polynomial functions that have been traditionally used for modeling corneal surfaces may not necessarily correctly represent given corneal surface data in terms of its optical performance, we introduced the concept of Zernike polynomial-based rational functions. Modeling optimality criteria were employed in terms of both the rms surface error as well as the point spread function cross-correlation. The parameters of approximations were estimated using a nonlinear least-squares procedure based on the Levenberg-Marquardt algorithm. A large number of retrospective videokeratoscopic measurements were used to evaluate the performance of the proposed rational-function-based modeling approach. The results indicate that the rational functions almost always outperform the traditional Zernike polynomial approximations with the same number of coefficients.

Fully automated corneal endothelial morphometry of images captured by clinical specular microscopy

NASA Astrophysics Data System (ADS)

Bucht, Curry; Söderberg, Per; Manneberg, Göran

2009-02-01

The corneal endothelium serves as the posterior barrier of the cornea. Factors such as clarity and refractive properties of the cornea are in direct relationship to the quality of the endothelium. The endothelial cell density is considered the most important morphological factor. Morphometry of the corneal endothelium is presently done by semi-automated analysis of pictures captured by a Clinical Specular Microscope (CSM). Because of the occasional need of operator involvement, this process can be tedious, having a negative impact on sampling size. This study was dedicated to the development of fully automated analysis of images of the corneal endothelium, captured by CSM, using Fourier analysis. Software was developed in the mathematical programming language Matlab. Pictures of the corneal endothelium, captured by CSM, were read into the analysis software. The software automatically performed digital enhancement of the images. The digitally enhanced images of the corneal endothelium were transformed, using the fast Fourier transform (FFT). Tools were developed and applied for identification and analysis of relevant characteristics of the Fourier transformed images. The data obtained from each Fourier transformed image was used to calculate the mean cell density of its corresponding corneal endothelium. The calculation was based on well known diffraction theory. Results in form of estimated cell density of the corneal endothelium were obtained, using fully automated analysis software on images captured by CSM. The cell density obtained by the fully automated analysis was compared to the cell density obtained from classical, semi-automated analysis and a relatively large correlation was found.

Regeneration of Corneal Epithelium With Dental Pulp Stem Cells Using a Contact Lens Delivery System.

PubMed

Kushnerev, Evgeny; Shawcross, Susan G; Sothirachagan, Shankari; Carley, Fiona; Brahma, Arun; Yates, Julian M; Hillarby, M Chantal

2016-10-01

The corneal epithelium is sloughed off surface of the eye by the action of blinking and is continually replaced by division and maturation of the limbal stem cells (LSCs). In the case of injury or disease, LSCs can be lost or damaged to a point at which the corneal epithelial layer is no longer maintained. leading to LSC deficiencies (LSCDs). When this occurs, the opaque conjunctiva overgrows the anterior surface of the eye, leading to vision impairment or loss. Dental pulp stem cells (DPSCs) are promising candidates as autologous LSC substitutes. In this study, contact lenses (CLs) are used as a novel medical device to deliver DPSCs onto corneal surface to enhance corneal epithelium regeneration. Dental pulp stem cells labeled with green fluorescent Qtracker 525 were seeded onto the pretreated CLs, allowed to adhere, then delivered to debrided human corneas. Expression of KRT3, 12, 13, and 19 was investigated by immunostaining, then standard and confocal microscopy. Dental pulp stem cells were successfully isolated, labeled, and delivered to the corneal surface using CLs. Following removal of CLs, confocal microscopy showed that the DPSCs had migrated onto the cornea. Coexpression of KRT12 and green fluorescent Qtracker 525 confirmed that the DPSCs had transdifferentiated into corneal epithelial progenitors. Delimitation of KRT 19 and green fluorescence provides evidence that Qtracker 525-labeled DPSCs establish a barrier to the invasion of the cornea by conjunctiva. In this study we show that DPSCs, delivered using CLs, can be used to enhance repair and regeneration of the human corneal epithelium.

Knowledge and Attitude Toward Corneal Donation Among High School Children in Northern India.

PubMed

Gupta, Parul Chawla; Duggal, Mona; Jamir, Limalemla; Sharma, Drishti; Kankaria, Ankita; Sathyanath, Shreyaswi; Kaur, Rupinder; Rana, Kirtan; Ram, Jagat

2017-05-01

To assess the knowledge and attitude of school-going adolescents regarding corneal donation in government and private schools in an urban area of Northern India. A school-based cross-sectional study was conducted in an urban field practice area of Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. A total of 365 participants of the seventh to 10th grade were enrolled from a government school and a private school. A pretested, semistructured, self-administered, bilingual (English and Hindi) questionnaire was used to assess the sociodemographic profile and knowledge and attitude related to corneal donation. Most (87%) (confidence interval, 83.1%-90.0%) participants had heard about corneal donation. Only 2% of students answered all the knowledge-related questions correctly. None knew about the national toll-free number for corneal donation. Three-fourth (72%) supported the idea of corneal donation. Of them, only 44% (confidence interval, 41.0-47.1) were willing to pledge to donate their own eyes. Fears and myths were the persistent barriers. The government and private schools differed in both knowledge and attitude, with the latter performing better. Knowledge among the selected high school children was poor. Although many supported the idea, only a few were willing to donate. We suggest that program components be evaluated from time to time. Future studies should explore the role of strengthening Information Education and Communication (IEC) activities among high school students for motivating community members to pledge to donate for corneal donation.

[Design and Realization of Personalized Corneal Analysis Software Based on Corneal Topography System].

PubMed

Huang, Xueping; Xie, Zhonghao; Cen, Qin; Zheng, Suilian

2016-08-01

As the most important refraction part in the optical system,cornea possesses characteristics which are important parameters in ophthalmology clinical surgery.During the measurement of the cornea in our study,we acquired the corneal data of Orbscan Ⅱ corneal topographer in real time using the Hook technology under Windows,and then took the data into the corneal analysis software.We then further analyzed and calculated the data to obtain individual Q-value of overall corneal 360semi-meridian.The corneal analysis software took Visual C++ 6.0as development environment,used OpenGL graphics technology to draw three-dimensional individual corneal morphological map and the distribution curve of the Q-value,and achieved real-time corneal data query.It could be concluded that the analysis would further extend the function of the corneal topography system,and provide a solid foundation for the further study of automatic screening of corneal diseases.

Managing Sjögren’s Syndrome and non-Sjögren Syndrome dry eye with anti-inflammatory therapy

PubMed Central

Coursey, Terry G; de Paiva, Cintia S

2014-01-01

Dry eye from Sjögren’s syndrome is a multifactorial disease that results in dysfunction of the lacrimal functional unit. Studies have shown changes in tear composition, including inflammatory cytokines, chemokines, and metalloproteinase. T-lymphocytes have been shown to increase in the conjunctiva and lacrimal glands in patient and animal models. This inflammation is in part responsible for the pathogenesis of the disease, which results in symptoms of eye irritation, ocular surface epithelial disease, and loss of corneal barrier function. There are a number of anti-inflammatory approaches for treating this disease. The current study reviews details of immune response and anti–inflammatory therapies used to control this disease. PMID:25120351

Fluorouracil as a treatment for corneal papilloma in a Malayan tapir.

PubMed

Karpinski, Lorraine G; Miller, Christine L

2002-09-01

A 26-year-old, wild caught, male Malayan tapir at the Miami Metrozoo with bilateral corneal papillomas was serially immobilized and given subconjunctival injections of fluorouracil. Over the course of 17 weeks five bilateral injections of 25 mg fluorouracil were given. This treatment caused regression of the corneal lesions as evidenced by decreased lesion diameter, decreased corneal vascularity, increased corneal clarity, and improved visual function. No adverse drug effects were observed.

Fully automated corneal endothelial morphometry of images captured by clinical specular microscopy

NASA Astrophysics Data System (ADS)

Bucht, Curry; Söderberg, Per; Manneberg, Göran

2010-02-01

The corneal endothelium serves as the posterior barrier of the cornea. Factors such as clarity and refractive properties of the cornea are in direct relationship to the quality of the endothelium. The endothelial cell density is considered the most important morphological factor of the corneal endothelium. Pathological conditions and physical trauma may threaten the endothelial cell density to such an extent that the optical property of the cornea and thus clear eyesight is threatened. Diagnosis of the corneal endothelium through morphometry is an important part of several clinical applications. Morphometry of the corneal endothelium is presently carried out by semi automated analysis of pictures captured by a Clinical Specular Microscope (CSM). Because of the occasional need of operator involvement, this process can be tedious, having a negative impact on sampling size. This study was dedicated to the development and use of fully automated analysis of a very large range of images of the corneal endothelium, captured by CSM, using Fourier analysis. Software was developed in the mathematical programming language Matlab. Pictures of the corneal endothelium, captured by CSM, were read into the analysis software. The software automatically performed digital enhancement of the images, normalizing lights and contrasts. The digitally enhanced images of the corneal endothelium were Fourier transformed, using the fast Fourier transform (FFT) and stored as new images. Tools were developed and applied for identification and analysis of relevant characteristics of the Fourier transformed images. The data obtained from each Fourier transformed image was used to calculate the mean cell density of its corresponding corneal endothelium. The calculation was based on well known diffraction theory. Results in form of estimated cell density of the corneal endothelium were obtained, using fully automated analysis software on 292 images captured by CSM. The cell density obtained by the fully automated analysis was compared to the cell density obtained from classical, semi-automated analysis and a relatively large correlation was found.

Osmolarity of prevalent eye drops, side effects, and therapeutic approaches.

PubMed

Dutescu, Ralf M; Panfil, Claudia; Schrage, Norbert

2015-05-01

Little is known about how the osmolarity of ophthalmic formulations affects the ocular surface. Because hyperosmolar eye drops could be therapeutic for treating corneal edema, this article presents an ex vivo model of corneal edema for testing ophthalmic drugs based on their osmolarity. The respective osmolarity of common eye drops found in the German market is also analyzed here. For modeling corneal edema, an Ex Vivo Eye Irritation Test was used to simulate an ocular anterior chamber with a physiological corneal barrier. To induce corneal edema, the anterior chamber was supplied with a hypoosmolar medium (148 mOsm/L) for 24 hours. Preserved and preservative-free 5% sodium chloride (hyperosmolar Omnisorb and Ocusalin 5% UD) were used for 1 hour, on 5 corneas each, to test their efficiency to reduce corneal edema in this model. Corneal thickness was determined by optical coherence tomography. Osmolarity of 87 common eye drops was measured by freezing point osmometry. Ex vivo, the tested hypoosmolar condition induced corneal edema from 450 μm (±50 μm) at baseline to 851 μm (±94 μm, P < 0.0001). Omnisorb and Ocusalin 5% UD significantly reduced the corneal thickness by 279 μm (±28 μm, P < 0.001) for Omnisorb and 258 μm (±29 μm, P < 0.001) for Ocusalin 5% UD. Forty-three (49%) of the tested products had an osmolarity below and 44 (51%) above the physiological tear osmolarity of 289 mOsm/L. Osmolarity values of less than 200 mOsm/L were found in lubricant drops. The highest osmolarity was detected in Omnisorb (1955 mOsm/L). The Ex Vivo Eye Irritation Test has proven to be a reliable novel model of corneal edema for evaluating osmotic eye drops. Osmolarity measurements revealed a wide range from hypotonic to hypertonic formulations for commonly marketed ophthalmic drugs.

Design of Novel Ophthalmic Formulation Containing Drug Nanoparticles and Its Usefulness as Anti-glaucoma Drugs.

PubMed

Nagai, Noriaki

2016-01-01

The ophthalmic application of drugs is the primary route of administration for the therapy of glaucoma; however, in traditional formulations, only small amounts of the administered drug penetrate the cornea to reach the desired intraocular tissue due to corneal barriers. Recently, nanoparticulate drug delivery is expected as a technology to overcome the difficulties in delivering drugs across biological barriers (improvement of bioavailability). In this study, we attempted to establish a new method for preparing solid drug nanoparticles by using a bead mill and various additives, and succeeded in preparing a high quality dispersion containing drug nanoparticles. For a more concrete example, a mean particle size of disulfiram (DSF) treated with bead mill is 183 nm. The corneal penetration and corneal residence time of DSF from the ophthalmic dispersion containing DSF nanoparticles were significantly higher than those from a 2-hydroxypropyl-β-cyclodextrin solution containing DSF (DSF solution). It is known that the administration of DSF has intraocular pressure (IOP)-reducing effects. The IOP-reducing effects of the ophthalmic dispersion containing DSF nanoparticles were significantly greater than those of the DSF solution in rabbits (the IOP was enhanced by placing the rabbits in a dark room for 5 h). In addition, the ophthalmic dispersion containing DSF nanoparticles is better tolerated by corneal epithelial cells than DSF solution. It is possible that dispersions containing DSF nanoparticles provide new possibilities for effectively treating glaucoma, and that ocular drug delivery systems using drug nanoparticles may expand their usage for therapy in the ophthalmologic field.

Corneal and conjunctival epithelial staining in hydrogel contact lens wearers.

PubMed

Brautaset, Rune L; Nilsson, Maria; Leach, Norman; Miller, William L; Gire, Anisa; Quintero, Sam; Bergmanson, Jan P G

2008-11-01

The purpose of this study was to investigate the prevalence of conjunctival and corneal epithelial staining in soft contact lens wearers and to see if staining could be associated with factors such as type of lens worn, wearing time, care system, age, and sex. The records of 338 adapted hydrogel contact lens wearers were examined retrospectively. Conjunctival staining was found to be present in 32.5% of the subjects and corneal staining was found to be present in 19.5% of subjects. None of the subjects had staining above grade 2 using the Cornea and Contact Lens Research Unit scale. Because of the low prevalence of staining, the low grading of staining found and the large variation in refractive power, lens type worn, wearing modality, and solution used statistical analysis for association between staining and different factors could only be performed for the association between sex and staining and between corneal and conjunctival staining. However, no statistical significant association could be demonstrated. Despite the low prevalence of staining the conjunctiva and cornea should be examined carefully in contact lens wearers and prospective wearers because the conjunctival and corneal epithelium serve as protective barriers for the underlying layers of the cornea and conjunctiva. To allow comparison of data obtained in different studies assessing corneal staining, it is recommended that clinicians develop and adopt a universal standard protocol for this measure.

Construction of a human corneal stromal equivalent with non-transfected human corneal stromal cells and acellular porcine corneal stromata.

PubMed

Diao, Jin-Mei; Pang, Xin; Qiu, Yue; Miao, Ying; Yu, Miao-Miao; Fan, Ting-Jun

2015-03-01

A tissue-engineered human corneal stroma (TE-HCS) has been developed as a promising equivalent to the native corneal stroma for replacement therapy. However, there is still a crucial need to improve the current approaches to render the TE-HCS equivalent more favorable for clinical applications. At the present study, we constructed a TE-HCS by incubating non-transfected human corneal stromal (HCS) cells in an acellular porcine corneal stromata (aPCS) scaffold in 20% fetal bovine serum supplemented DMEM/F12 (1:1) medium at 37 °C with 5% CO2in vitro. After 3 days of incubation, the constructed TE-HCS had a suitable tensile strength for transplantation, and a transparency that is comparable to native cornea. The TE-HCS had a normal histological structure which contained regularly aligned collagen fibers and differentiated HCS cells with positive expression of marker and functional proteins, mimicking a native HCS. After transplantation into rabbit models, the TE-HCS reconstructed normal corneal stroma in vivo and function well in maintaining corneal clarity and thickness, indicating that the completely biological TE-HCS could be used as a HCS equivalent. The constructed TE-HCS has promising potentials in regenerative medicine and treatment of diseases caused by corneal stromal disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Non-Invasive Evaluation of Corneal Abnormalities Using Static and Dynamic Light Scattering

NASA Technical Reports Server (NTRS)

Ansari, Rafat R.; Misra, Anup K.; Leung, Alfred B.; King, James F.; Datiles, Manuel B., III

2002-01-01

A preliminary study of corneal abnormalities in intact bovine eyes is presented. Twenty-one eyes were treated with chemicals, cotton swabs, and radial and photo-refractive surgeries. Dynamic and static light scattering was performed as a function of the penetration depth into the corneal tissue. Topographical maps of corneal refractive power from untreated and treated corneas were also obtained using videokeratoscopy and results compared. The ultimate aim is to develop the technique of dynamic light scattering (DLS) for clinical applications in early evaluation of corneal complications after laser-assisted in situ keratomileusis (LASIK) surgeries and other corneal abnormalities.

Noninvasive evaluation of corneal abnormalities using static and dynamic light scattering

NASA Astrophysics Data System (ADS)

Ansari, Rafat R.; Misra, Anup K.; Leung, Alfred B.; King, James F.; Datiles, Manuel B., III

2002-06-01

A preliminary study of corneal abnormalities in intact bovine eyes is presented. Twenty-one eyes were treated with chemicals, cotton swabs, and radial and photo-refractive surgeries. Dynamic and static light scattering was performed as a function of the penetration depth into the corneal tissue. Topographical maps of corneal refractive power from untreated and treated corneas were also obtained using videokeratoscopy and results compared. The ultimate aim is to develop the technique of dynamic light scattering (DLS) for clinical applications in early evaluation of corneal complications after laser-assisted in situ keratomileusis (LASIK) surgeries and other corneal abnormalities.

Safety Profile of Stromal Hydration of Clear Corneal Incisions with Cefuroxime in the Mouse Model.

PubMed

Moosajee, Mariya; Tracey-White, Dhani; Harbottle, Richard P; Ferguson, Veronica

2016-09-01

The use of sutureless clear corneal incisions (CCIs) for phacoemulsification is an established surgical technique, but the dynamic morphology of the wound and poor construction can lead to an increased risk of postoperative endophthalmitis. Stromal hydration with balanced salt solution (BSS) can improve the self-sealing status. Intracameral cefuroxime has reduced endophthalmitis rates. This study investigates the safety profile of stromal hydration with cefuroxime, as sequestering antibiotic at the wound may potentially provide added protection against infection. MF-1 mice underwent bilateral CCI, followed by stromal hydration with 5 μL of 10 mg/mL cefuroxime, cefuroxime-texas red conjugate (for detection using confocal microscopy), or BSS. Corneas were harvested from 1 h to 12 weeks postoperatively; gross morphology, histology, and apoptotic cell death levels were investigated to determine the safety profile. Bactericidal activity of cefuroxime was assayed using homogenized whole cornea following stromal hydration at 1 h, 24 h, and day 7 against gram-negative Escherichia coli. Cefuroxime stromal hydration did not alter corneal morphology, with no evidence of corneal scarring or vascularization. Corneal histology and levels of apoptosis were minimal and comparable to the BSS groups up to 12 weeks. Confocal microscopy detected cefuroxime-texas red up to 1 week surrounding the corneal wound. Whole corneal tissue homogenates displayed bactericidal activity up to 24 h postoperatively. Stromal hydration of CCI with cefuroxime is safe in mouse corneas. A reservoir of antibiotic at the wound can potentially act as a barrier of defense against infection following cataract and associated ocular surgery.

Identification of Therapeutic Targets of Inflammatory Monocyte Recruitment to Modulate the Allogeneic Injury to Donor Cornea.

PubMed

Lapp, Thabo; Zaher, Sarah S; Haas, Carolin T; Becker, David L; Thrasivoulou, Chris; Chain, Benjamin M; Larkin, Daniel F P; Noursadeghi, Mahdad

2015-11-01

We sought to test the hypothesis that monocytes contribute to the immunopathogenesis of corneal allograft rejection and identify therapeutic targets to inhibit monocyte recruitment. Monocytes and proinflammatory mediators within anterior chamber samples during corneal graft rejection were quantified by flow cytometry and multiplex protein assays. Lipopolysaccharide or IFN-γ stimulation of monocyte-derived macrophages (MDMs) was used to generate inflammatory conditioned media (CoM). Corneal endothelial viability was tested by nuclear counting, connexin 43, and propidium iodide staining. Chemokine and chemokine receptor expression in monocytes and MDMs was assessed in microarray transcriptomic data. The role of chemokine pathways in monocyte migration across microvascular endothelium was tested in vitro by chemokine depletion or chemokine receptor inhibitors. Inflammatory monocytes were significantly enriched in anterior chamber samples within 1 week of the onset of symptoms of corneal graft rejection. The MDM inflammatory CoM was cytopathic to transformed human corneal endothelia. This effect was also evident in endothelium of excised human cornea and increased in the presence of monocytes. Gene expression microarrays identified monocyte chemokine receptors and cognate chemokines in MDM inflammatory responses, which were also enriched in anterior chamber samples. Depletion of selected chemokines in MDM inflammatory CoM had no effect on monocyte transmigration across an endothelial blood-eye barrier, but selective chemokine receptor inhibition reduced monocyte recruitment significantly. We propose a role for inflammatory monocytes in endothelial cytotoxicity in corneal graft rejection. Therefore, targeting monocyte recruitment offers a putative novel strategy to reduce donor endothelial cell injury in survival of human corneal allografts.

Investigation of Overrun-Processed Porous Hyaluronic Acid Carriers in Corneal Endothelial Tissue Engineering

PubMed Central

Lai, Jui-Yang; Cheng, Hsiao-Yun; Ma, David Hui-Kang

2015-01-01

Hyaluronic acid (HA) is a linear polysaccharide naturally found in the eye and therefore is one of the most promising biomaterials for corneal endothelial regenerative medicine. This study reports, for the first time, the development of overrun-processed porous HA hydrogels for corneal endothelial cell (CEC) sheet transplantation and tissue engineering applications. The hydrogel carriers were characterized to examine their structures and functions. Evaluations of carbodiimide cross-linked air-dried and freeze-dried HA samples were conducted simultaneously for comparison. The results indicated that during the fabrication of freeze-dried HA discs, a technique of introducing gas bubbles in the aqueous biopolymer solutions can be used to enlarge pore structure and prevent dense surface skin formation. Among all the groups studied, the overrun-processed porous HA carriers show the greatest biological stability, the highest freezable water content and glucose permeability, and the minimized adverse effects on ionic pump function of rabbit CECs. After transfer and attachment of bioengineered CEC sheets to the overrun-processed HA hydrogel carriers, the therapeutic efficacy of cell/biopolymer constructs was tested using a rabbit model with corneal endothelial dysfunction. Clinical observations including slit-lamp biomicroscopy, specular microscopy, and corneal thickness measurements showed that the construct implants can regenerate corneal endothelium and restore corneal transparency at 4 weeks postoperatively. Our findings suggest that cell sheet transplantation using overrun-processed porous HA hydrogels offers a new way to reconstruct the posterior corneal surface and improve endothelial tissue function. PMID:26296087

Protein-Based Drug-Delivery Materials.

PubMed

Jao, Dave; Xue, Ye; Medina, Jethro; Hu, Xiao

2017-05-09

There is a pressing need for long-term, controlled drug release for sustained treatment of chronic or persistent medical conditions and diseases. Guided drug delivery is difficult because therapeutic compounds need to survive numerous transport barriers and binding targets throughout the body. Nanoscale protein-based polymers are increasingly used for drug and vaccine delivery to cross these biological barriers and through blood circulation to their molecular site of action. Protein-based polymers compared to synthetic polymers have the advantages of good biocompatibility, biodegradability, environmental sustainability, cost effectiveness and availability. This review addresses the sources of protein-based polymers, compares the similarity and differences, and highlights characteristic properties and functionality of these protein materials for sustained and controlled drug release. Targeted drug delivery using highly functional multicomponent protein composites to guide active drugs to the site of interest will also be discussed. A systematical elucidation of drug-delivery efficiency in the case of molecular weight, particle size, shape, morphology, and porosity of materials will then be demonstrated to achieve increased drug absorption. Finally, several important biomedical applications of protein-based materials with drug-delivery function-including bone healing, antibiotic release, wound healing, and corneal regeneration, as well as diabetes, neuroinflammation and cancer treatments-are summarized at the end of this review.

What is the Best Strategy on Detection of Cornea Neuropathy in People with Diabetes? Recent Advances in Potential Measurements.

PubMed

Lv, Ying; Zhao, Shaozhen

2018-03-26

There are well-acknowledged clinical or pre-clinical measurements concerning diabetic peripheral neuropathy(DPN). The current gold standard for diagnosis of diabetic peripheral neuropathy is nerve conduction suitable for detecting large nerve fiber function[1] and intraepidermal nerve fiber density assessment for small fiber damage evaluation[2]. The lack of a sensitive, non-invasive, and repeatable endpoint to measure changes in small nerve fibers is a major factor holding back clinical trials for the treatment of diabetic peripheral neuropathy. As cornea is the most densely innerved tissue, assessing corneal nerves' structure and function will be promising to predict and assess the degree of DPN [3]. In the diabetic micro-environment, damaged corneal nerves lead to decreased corneal sensitivity, both of which resulting in abnormal tear function. According to this theory, the measurements of nerve structure, corneal sensitivity, tear secretion and tear components, to some extent, can reveal and assess the state of corneal neuropathy. This review focuses on summarizing the knowledge of the latest detective methods of diabetic corneal neuropathy, popular in use or possible to further in study and be applied into clinical practice. Copyright © 2018 Elsevier B.V. All rights reserved.

Biocompatibility of helicoidal multilamellar arginine-glycine-aspartic acid-functionalized silk biomaterials in a rabbit corneal model.

PubMed

Wang, Liqiang; Ma, Ruijue; Du, Gaiping; Guo, Huiling; Huang, Yifei

2015-01-01

Silk proteins represent a unique choice in the selection of biomaterials that can be used for corneal tissue engineering and regenerative medical applications. We implanted helicoidal multilamellar arginine-glycine-aspartic acid-functionalized silk biomaterials into the corneal stroma of rabbits, and evaluated its biocompatibility. The corneal tissue was examined after routine hematoxylin-eosin staining, immunofluorescence for collagen I and III, and fibronectin, and scanning electron microscopy. The silk films maintained their integrity and transparency over the 180-day experimental period without causing immunogenic and neovascular responses or degradation of the rabbit corneal stroma. Collagen I increased, whereas Collagen III and fibronectin initially increased and then gradually decreased. The extracellular matrix deposited on the surface of the silk films, tightly adhered to the biomaterial. We have shown this kind of silk film graft has suitable biocompatibility with the corneal stroma and is an initial step for clinical trials to evaluate this material as a transplant biomaterial for keratoplasty tissue constructs. © 2014 Wiley Periodicals, Inc.

Cling film as a barrier against CJD in corneal contact A-scan ultrasonography.

PubMed

Rani, Asha; Dunne, Mark C M; Barnes, Derek A

2003-01-01

To determine the validity of covering a corneal contact transducer probe with cling film as protection against the transmission of Creutzfeldt-Jakob disease (CJD). The anterior chamber depth, lens thickness and vitreous chamber depth of the right eyes of 10 subjects was recorded, under cycloplegia, with and without cling film covering over the transducer probe of a Storz Omega Compu-scan Biometric Ruler. Measurements were repeated on two occasions. Cling film covering did not influence bias or repeatability. Although the 95% limits of agreement between measurements made with and without cling film covering tended to exceed the intrasessional repeatability, they did not exceed the intersessional repeatability of measurements taken without cling film. The results support the use of cling film as a disposable covering for corneal contact A-scan ultrasonography to avoid the risk of spreading CJD from one subject to another.

Corneal Regeneration After Photorefractive Keratectomy: A Review☆

PubMed Central

Tomás-Juan, Javier; Murueta-Goyena Larrañaga, Ane; Hanneken, Ludger

2014-01-01

Photorefractive keratectomy (PRK) remodels corneal stroma to compensate refractive errors. The removal of epithelium and the ablation of stroma provoke the disruption of corneal nerves and a release of several peptides from tears, epithelium, stroma and nerves. A myriad of cytokines, growth factors, and matrix metalloproteases participate in the process of corneal wound healing. Their balance will determine if reepithelization and stromal remodeling are appropriate. The final aim is to achieve corneal transparency for restoring corneal function, and a proper visual quality. Therefore, wound-healing response is critical for a successful refractive surgery. Our goal is to provide an overview into how corneal wounding develops following PRK. We will also review the influence of intraoperative application of mitomycin C, bandage contact lenses, anti-inflammatory and other drugs in preventing corneal haze and post-PRK pain. PMID:25444646

In vitro 3D corneal tissue model with epithelium, stroma, and innervation.

PubMed

Wang, Siran; Ghezzi, Chiara E; Gomes, Rachel; Pollard, Rachel E; Funderburgh, James L; Kaplan, David L

2017-01-01

The interactions between corneal nerve, epithelium, and stroma are essential for maintaining a healthy cornea. Thus, corneal tissue models that more fully mimic the anatomy, mechanical properties and cellular components of corneal tissue would provide useful systems to study cellular interactions, corneal diseases and provide options for improved drug screening. Here a corneal tissue model was constructed to include the stroma, epithelium, and innervation. Thin silk protein film stacks served as the scaffolding to support the corneal epithelial and stromal layers, while a surrounding silk porous sponge supported neuronal growth. The neurons innervated the stromal and epithelial layers and improved function and viability of the tissues. An air-liquid interface environment of the corneal tissue was also mimicked in vitro, resulting in a positive impact on epithelial maturity. The inclusion of three cell types in co-culture at an air-liquid interface provides an important advance for the field of in vitro corneal tissue engineering, to permit improvements in the study of innervation and corneal tissue development, corneal disease, and tissue responses to environmental factors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Long-term consequences of topical dexamethasone treatment during acute corneal HSV-1 infection on the immune system

PubMed Central

Chucair-Elliott, Ana J.; Carr, Meghan M.; Carr, Daniel J. J.

2017-01-01

Herpes simplex virus type 1 (HSV-1) is a leading cause of neurotrophic keratitis (NTK). NTK is characterized by decreased corneal sensation from damage to the corneal sensory fibers. We have reported on the regression of corneal nerves and their function during acute HSV-1 infection. That nerve loss is followed by an aberrant process of nerve regeneration during the latent phase of infection that lacks functional recovery. We recently showed the elicited immune response in the infected cornea, and not viral replication itself, is part of the mechanism responsible for the nerve degeneration process after infection. Specifically, we showed infected corneas topically treated with dexamethasone (DEX) significantly retained both structure and sensitivity of the corneal nerve network in comparison to mice treated with control eye drops, consistent with decreased levels of proinflammatory cytokines and reduced influx of macrophages and CD8+ T cells into the cornea. This study was undertaken to analyze the long-term effect of such a localized, immunosuppressive paradigm (DEX drops on the cornea surface during the first 8 d of HSV-1 infection) on the immune system and on corneal pathology. We found the profound immunosuppressive effect of DEX on lymphoid tissue was sustained in surviving mice for up to 30 d postinfection (p.i.). DEX treatment had prolonged effects, preserving corneal innervation and its function and blunting neovascularization, as analyzed at 30 d p.i. Our data support previously reported observations of an association between the persistent presence of inflammatory components in the latently infected cornea and structural and functional nerve defects in NTK. PMID:28115476

University students' knowledge of corneal donation and willingness to donate corneas in the occupied Palestinian territory: a cross-sectional study.

PubMed

Al-Labadi, Liana; Gammoh, Yazan; Shehada, Reham; Shahin, Reem; Jbarah, Walaa; Amro, Madleen; Athamny, Hanan

2018-02-21

Access to corneal transplantation is limited worldwide because of poor knowledge. Ethical, religious, and cultural barriers contribute to low rates of corneal donation. In the occupied Palestinian territory, limited information is available on factors affecting corneal donation. The aim of this study was to assess the knowledge and willingness towards corneal donation in Palestinian students. This cross-sectional study included university students selected through convenience sampling in Nablus in the summer of 2016. The sample size was determined using the sample formulae and a 15% non-response rate. All students registered in obligatory courses were included in the study after verbal consent. Each participant was given a self-administered questionnaire consisting of 14 questions to assess knowledge, awareness, and willingness toward corneal donation. Frequencies were used for descriptive analysis, and associations were determined using multivariate analysis and χ 2 test, with a p value of less than 0·05 considered significant. Of the 634 students completing the questionnaire, 411 (65%) were women, 614 (97%) were Muslims, and 155 (25%) were health or medical students. 592 (93%) respondents were unaware of eye bank availability, and 407 (69%; p=0.002) of these respondents did not show willingness towards corneal donation. 431 (67%) respondents were aware of a lack in corneal donation, but 274 (64%; p=0·01) of these respondents did not show willingness towards corneal donation. 429 (68%) respondents were not willing to donate their corneas, the most common reasons being disapproval by family members and poor awareness. We found no association between sociodemographic factors and willingness was determined. Palestinian students are aware of the lack of local cornea donation but are unwilling to donate their corneas. The study results are not representative of the entire population because of the homogeneous nature of the sample. Large efforts are needed locally to develop the eye bank infrastructure to increase knowledge and awareness relating to corneal donation. None. Copyright © 2018 Elsevier Ltd. All rights reserved.

Corneal Regeneration After Photorefractive Keratectomy: A Review.

PubMed

Tomás-Juan, Javier; Murueta-Goyena Larrañaga, Ane; Hanneken, Ludger

2015-01-01

Photorefractive keratectomy (PRK) remodels corneal stroma to compensate refractive errors. The removal of epithelium and the ablation of stroma provoke the disruption of corneal nerves and a release of several peptides from tears, epithelium, stroma and nerves. A myriad of cytokines, growth factors, and matrix metalloproteases participate in the process of corneal wound healing. Their balance will determine if reepithelization and stromal remodeling are appropriate. The final aim is to achieve corneal transparency for restoring corneal function, and a proper visual quality. Therefore, wound-healing response is critical for a successful refractive surgery. Our goal is to provide an overview into how corneal wounding develops following PRK. We will also review the influence of intraoperative application of mitomycin C, bandage contact lenses, anti-inflammatory and other drugs in preventing corneal haze and post-PRK pain. Copyright © 2014 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

Trehalose protects against ocular surface disorders in experimental murine dry eye through suppression of apoptosis.

PubMed

Chen, Wei; Zhang, Xiaobo; Liu, Mimi; Zhang, Jingna; Ye, Ya; Lin, Ying; Luyckx, Jacques; Qu, Jia

2009-09-01

The disaccharide trehalose is a key element involved in anhydrobiosis (the capability of surviving almost complete dehydration) in many organisms. Its presence also confers resistance to desiccation and high osmolarity in bacterial and human cells by protecting proteins and membranes from denaturation. The present study used a novel murine dry eye model induced by controlled low-humidity air velocity to determine whether topically applied trehalose could heal ocular surface epithelial disorders caused by ocular surface desiccation. In addition, the efficacy of 87.6 mM trehalose eyedrops was compared with that of 20% serum, the efficacy of which has been well documented. Mice ocular surface epithelial disorders were induced by exposure of murine eyes to continuous controlled low-humidity air velocity in an intelligently controlled environmental system (ICES) for 21 days, which accelerated the tear evaporation. The mice were then randomized into three groups: the control group received PBS (0.01 M) treatment; a second group received 87.6 mM trehalose eyedrops treatment; and the third group received mice serum eyedrops treatment. Each treatment was administered as a 10 microl dose every 6 h for 14 days. The resultant changes in corneal barrier function and histopathologic examination of cornea and conjunctiva were analyzed and the level of apoptosis on the ocular surface was assessed using active caspase-3. After 14 days of treatment, the corneal fluorescein staining area, the ruffling and desquamating cells on the apical corneal epithelium, as well as the apoptotic cells on ocular surface epithelium had significantly reduced in eyes treated with trehalose compared with those treated with serum and PBS. In contrast, after 14 days of treatment, improvements in the thickness of the corneal epithelium, the squamous metaplasia in conjunctival epithelium and the number of goblet cells of the conjunctiva were less marked in eyes treated with trehalose compared with serum. These results demonstrated that trehalose could improve the appearance of ocular surface epithelial disorders due to desiccation through suppression of apoptosis. Trehalose produces some of the same responses as serum upon topical application and can maintain corneal health.

Neurotrophic factors and corneal nerve regeneration

PubMed Central

Sacchetti, Marta; Lambiase, Alessandro

2017-01-01

The cornea has unique features that make it a useful model for regenerative medicine studies. It is an avascular, transparent, densely innervated tissue and any pathological changes can be easily detected by slit lamp examination. Corneal sensitivity is provided by the ophthalmic branch of the trigeminal nerve that elicits protective reflexes such as blinking and tearing and exerts trophic support by releasing neuromediators and growth factors. Corneal nerves are easily evaluated for both function and morphology using standard instruments such as corneal esthesiometer and in vivo confocal microscope. All local and systemic conditions that are associated with damage of the trigeminal nerve cause the development of neurotrophic keratitis, a rare degenerative disease. Neurotrophic keratitis is characterized by impairment of corneal sensitivity associated with development of persistent epithelial defects that may progress to corneal ulcer, melting and perforation. Current neurotrophic keratitis treatments aim at supporting corneal healing and preventing progression of corneal damage. Novel compounds able to stimulate corneal nerve recovery are in advanced development stage. Among them, nerve growth factor eye drops showed to be safe and effective in stimulating corneal healing and improving corneal sensitivity in patients with neurotrophic keratitis. Neurotrophic keratitis represents an useful model to evaluate in clinical practice novel neuro-regenerative drugs. PMID:28966630

Establishment of a Human Conjunctival Epithelial Cell Line Lacking the Functional Tacstd2 Gene (An American Ophthalmological Society Thesis)

PubMed Central

Kinoshita, Shigeru; Kawasaki, Satoshi; Kitazawa, Koji; Shinomiya, Katsuhiko

2012-01-01

Purpose: To report the establishment of a human conjunctival epithelial cell line lacking the functional tumor-associated calcium signal transducer 2 (TACSTD2) gene to be used as an in vitro model of gelatinous drop-like corneal dystrophy (GDLD), a rare disease in which the corneal epithelial barrier function is significantly compromized by the loss of function mutation of the TACSTD2 gene. Methods: A small piece of conjunctival tissue was obtained from a GDLD patient. The conjunctival epithelial cells were enzymatically separated and dissociated from the tissue and immortalized by the lentiviral introduction of the SV40 large T antigen and human telomerase reverse transcriptase (hTERT) genes. Population doubling, protein expression, and transepithelial resistance (TER) analyses were performed to assess the appropriateness of the established cell line as an in vitro model for GDLD. Results: The life span of the established cell line was found to be significantly elongated compared to nontransfected conjunctival epithelial cells. The SV40 large T antigen and hTERT genes were stably expressed in the established cell line. The protein expression level of the tight junction–related proteins was significantly low compared to the immortalized normal conjunctival epithelial cell line. TER of the established cell line was found to be significantly low compared to the immortalized normal conjunctival epithelial cell line. Conclusions: Our conjunctival epithelial cell line was successfully immortalized and well mimicked several features of GDLD corneas. This cell line may be useful for the elucidation of the pathogenesis of GDLD and for the development of novel treatments for GDLD. PMID:23818740

Expansion and cryopreservation of porcine and human corneal endothelial cells.

PubMed

Marquez-Curtis, Leah A; McGann, Locksley E; Elliott, Janet A W

2017-08-01

Impairment of the corneal endothelium causes blindness that afflicts millions worldwide and constitutes the most often cited indication for corneal transplants. The scarcity of donor corneas has prompted the alternative use of tissue-engineered grafts which requires the ex vivo expansion and cryopreservation of corneal endothelial cells. The aims of this study are to culture and identify the conditions that will yield viable and functional corneal endothelial cells after cryopreservation. Previously, using human umbilical vein endothelial cells (HUVECs), we employed a systematic approach to optimize the post-thaw recovery of cells with high membrane integrity and functionality. Here, we investigated whether improved protocols for HUVECs translate to the cryopreservation of corneal endothelial cells, despite the differences in function and embryonic origin of these cell types. First, we isolated endothelial cells from pig corneas and then applied an interrupted slow cooling protocol in the presence of dimethyl sulfoxide (Me 2 SO), with or without hydroxyethyl starch (HES). Next, we isolated and expanded endothelial cells from human corneas and applied the best protocol verified using porcine cells. We found that slow cooling at 1 °C/min in the presence of 5% Me 2 SO and 6% HES, followed by rapid thawing after liquid nitrogen storage, yields membrane-intact cells that could form monolayers expressing the tight junction marker ZO-1 and cytoskeleton F-actin, and could form tubes in reconstituted basement membrane matrix. Thus, we show that a cryopreservation protocol optimized for HUVECs can be applied successfully to corneal endothelial cells, and this could provide a means to address the need for off-the-shelf cryopreserved cells for corneal tissue engineering and regenerative medicine. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Cellular and nerve regeneration within a biosynthetic extracellular matrix for corneal transplantation

NASA Astrophysics Data System (ADS)

Li, Fengfu; Carlsson, David; Lohmann, Chris; Suuronen, Erik; Vascotto, Sandy; Kobuch, Karin; Sheardown, Heather; Munger, Rejean; Nakamura, Masatsugu; Griffith, May

2003-12-01

Our objective was to determine whether key properties of extracellular matrix (ECM) macromolecules can be replicated within tissue-engineered biosynthetic matrices to influence cellular properties and behavior. To achieve this, hydrated collagen and N-isopropylacrylamide copolymer-based ECMs were fabricated and tested on a corneal model. The structural and immunological simplicity of the cornea and importance of its extensive innervation for optimal functioning makes it an ideal test model. In addition, corneal failure is a clinically significant problem. Matrices were therefore designed to have the optical clarity and the proper dimensions, curvature, and biomechanical properties for use as corneal tissue replacements in transplantation. In vitro studies demonstrated that grafting of the laminin adhesion pentapeptide motif, YIGSR, to the hydrogels promoted epithelial stratification and neurite in-growth. Implants into pigs' corneas demonstrated successful in vivo regeneration of host corneal epithelium, stroma, and nerves. In particular, functional nerves were observed to rapidly regenerate in implants. By comparison, nerve regeneration in allograft controls was too slow to be observed during the experimental period, consistent with the behavior of human cornea transplants. Other corneal substitutes have been produced and tested, but here we report an implantable matrix that performs as a physiologically functional tissue substitute and not simply as a prosthetic device. These biosynthetic ECM replacements should have applicability to many areas of tissue engineering and regenerative medicine, especially where nerve function is required. regenerative medicine | tissue engineering | cornea | implantation | innervation

Corneal and conjunctival drug permeability: Systematic comparison and pharmacokinetic impact in the eye.

PubMed

Ramsay, Eva; Del Amo, Eva M; Toropainen, Elisa; Tengvall-Unadike, Unni; Ranta, Veli-Pekka; Urtti, Arto; Ruponen, Marika

2018-07-01

On the surface of the eye, both the cornea and conjunctiva are restricting ocular absorption of topically applied drugs, but barrier contributions of these two membranes have not been systemically compared. Herein, we studied permeability of 32 small molecular drug compounds across an isolated porcine cornea and built a quantitative structure-property relationship (QSPR) model for the permeability. Corneal drug permeability (data obtained for 25 drug molecules) showed a 52-fold range in permeability (0.09-4.70 × 10 -6  cm/s) and the most important molecular descriptors in predicting the permeability were hydrogen bond donor, polar surface area and halogen ratio. Corneal permeability values were compared to their conjunctival drug permeability values. Ocular drug bioavailability and systemic absorption via conjunctiva were predicted for this drug set with pharmacokinetic calculations. Drug bioavailability in the aqueous humour was simulated to be <5% and trans-conjunctival systemic absorption was 34-79% of the dose. Loss of drug across the conjunctiva to the blood circulation restricts significantly ocular drug bioavailability and, therefore, ocular absorption does not increase proportionally with the increasing corneal drug permeability. Copyright © 2018 Elsevier B.V. All rights reserved.

Alternatives to eye bank native tissue for corneal stromal replacement.

PubMed

Brunette, Isabelle; Roberts, Cynthia J; Vidal, François; Harissi-Dagher, Mona; Lachaine, Jean; Sheardown, Heather; Durr, Georges M; Proulx, Stéphanie; Griffith, May

2017-07-01

Corneal blindness is a major cause of blindness in the world and corneal transplantation is the only widely accepted treatment to restore sight in these eyes. However, it is becoming increasingly difficult for eye banks to meet the increasing demand for transplantable tissue, which is in part due to population aging. Donor tissue shortage is therefore a growing concern globally and there is a need for alternatives to human donor corneas. Biosynthetic corneal substitutes offer several significant advantages over native corneas: Large-scale production offers a powerful potential solution to the severe shortage of human donor corneas worldwide; Good manufacturing practices ensure sterility and quality control; Acellular corneal substitutes circumvent immune rejection induced by allogeneic cells; Optical and biomechanical properties of the implants can be adapted to the clinical need; and finally these corneal substitutes could benefit from new advances in biomaterials science, such as surface coating, functionalization and nanoparticles. This review highlights critical contributions from laboratories working on corneal stromal substitutes. It focuses on synthetic inert prostheses (keratoprostheses), acellular scaffolds with and without enhancement of endogenous regeneration, and cell-based replacements. Accent is put on the physical properties and biocompatibility of these biomaterials, on the functional and clinical outcome once transplanted in vivo in animal or human eyes, as well as on the main challenges of corneal stromal replacement. Regulatory and economic aspects are also discussed. All of these perspectives combined highlight the founding principles of the clinical application of corneal stromal replacement, a concept that has now become reality. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cellular Therapy With Human Autologous Adipose-Derived Adult Stem Cells for Advanced Keratoconus.

PubMed

Alió Del Barrio, Jorge L; El Zarif, Mona; de Miguel, María P; Azaar, Albert; Makdissy, Norman; Harb, Walid; El Achkar, Ibrahim; Arnalich-Montiel, Francisco; Alió, Jorge L

2017-08-01

The aim of this phase 1 study was to preliminarily evaluate the safety and efficacy of autologous adipose-derived adult stem cell (ADASC) implantation within the corneal stroma of patients with advanced keratoconus. Five consecutive patients were selected. Autologous ADASCs were obtained by elective liposuction. ADASCs (3 × 10) contained in 1 mL saline were injected into the corneal stroma through a femtosecond-assisted 9.5-mm diameter lamellar pocket under topical anesthesia. Patients were reviewed at 1 day, 1 week, 1, 3, and 6 months postoperatively. Visual function, manifest refraction, slit-lamp biomicroscopy, intraocular pressure, endothelial cell density, corneal topography, corneal optical coherence tomography, and corneal confocal biomicroscopy were recorded. No intraoperative or postoperative complications were recorded, with full corneal transparency recovery within 24 hours. Four patients completed the full follow-up. All patients improved their visual function (mean: 1 line of unaided and spectacle-corrected distance vision and 2 lines of rigid contact lens distance vision). Manifest refraction and topographic keratometry remained stable. Corneal optical coherence tomography showed a mean improvement of 16.5 μm in the central corneal thickness, and new collagen production was observed as patchy hyperreflective areas at the level of the stromal pocket. Confocal biomicroscopy confirmed the survival of the implanted stem cells at the surgical plane. Intraocular pressure and endothelial cell density remained stable. Cellular therapy of the human corneal stroma in vivo with autologous ADASCs appears to be safe. Stem cells survive in vivo with intrastromal new collagen production. Future studies with larger samples are required to confirm these preliminary results.

Regulation of human corneal epithelial mucins by rebamipide.

PubMed

Itoh, Shinsaku; Itoh, Kuni; Shinohara, Hisashi

2014-02-01

Membrane-associated mucins (MAMs) play important roles in barrier function and tear stability, and their expression on the ocular surface is altered in dry eye disease. Rebamipide is a mucin secretagogue that promotes the production of mucin-like glycoproteins in human corneal epithelial (HCE) cells. However, the expression of MAMs on the corneal epithelia (MUC1, MUC4, MUC16), which is induced by rebamipide, is poorly understood. In this study, we investigated the effect of rebamipide on the regulation of MAM expression in HCE cells. MUC16, Ki67 and PCNA expression levels in HCE cells isolated at confluence and at 24 hours after confluence were examined by Western blotting to assess cell proliferation. HCE cells isolated at 24 hours after confluence were cultured in medium supplemented with 1-10 µM rebamipide or 0.3-30 nM of epidermal growth factor (EGF). Real-time PCR (RT-PCR) and Western blot analysis of MAMs were performed to evaluate the effect of rebamipide. Western blot analysis of cells treated with an EGF receptor inhibitor (AG1478) or MEK1/2 inhibitor (U0126) was performed to reveal the relationship between EGF receptor activation and rebamipide-induced MAM expression. HCE cells isolated at 24 hours after confluence had lower cell proliferation activity and increased MUC16 expression compared with cells isolated at confluence. RT-PCR and Western blot analysis revealed that rebamipide increased MAM gene expression for 2 hours and protein expression for 24 hours in HCE cells. EGF inhibitor treatment led to reduced levels of all three MAMs that are normally induced by rebamipide, whereas EGF induced the expression of all three MAMs. We suggested that rebamipide increased MUC1, MUC4 and MUC16 expression levels through signals involved in EGF receptor activation in the human corneal epithelia. These data suggest that rebamipide may improve subjective symptoms of dry eye disease by upregulating MAM expression.

TRPV4 Regulates Tight Junctions and Affects Differentiation in a Cell Culture Model of the Corneal Epithelium.

PubMed

Martínez-Rendón, Jacqueline; Sánchez-Guzmán, Erika; Rueda, Angélica; González, James; Gulias-Cañizo, Rosario; Aquino-Jarquín, Guillermo; Castro-Muñozledo, Federico; García-Villegas, Refugio

2017-07-01

TRPV4 (transient receptor potential vanilloid 4) is a cation channel activated by hypotonicity, moderate heat, or shear stress. We describe the expression of TRPV4 during the differentiation of a corneal epithelial cell model, RCE1(5T5) cells. TRPV4 is a late differentiation feature that is concentrated in the apical membrane of the outmost cell layer of the stratified epithelia. Ca 2+ imaging experiments showed that TRPV4 activation with GSK1016790A produced an influx of calcium that was blunted by the specific TRPV4 blocker RN-1734. We analyzed the involvement of TRPV4 in RCE1(5T5) epithelial differentiation by measuring the development of transepithelial electrical resistance (TER) as an indicator of the tight junction (TJ) assembly. We showed that TRPV4 activity was necessary to establish the TJ. In differentiated epithelia, activation of TRPV4 increases the TER and the accumulation of claudin-4 in cell-cell contacts. Epidermal Growth Factor (EGF) up-regulates the TER of corneal epithelial cultures, and we show here that TRPV4 activation mimicked this EGF effect. Conversely, TRPV4 inhibition or knock down by specific shRNA prevented the increase in TER. Moreover, TRPP2, an EGF-activated channel that forms heteromeric complexes with TRPV4, is also concentrated in the outmost cell layer of differentiated RCE1(5T5) sheets. This suggests that the EGF regulation of the TJ may involve a heterotetrameric TRPV4-TRPP2 channel. These results demonstrated TRPV4 activity was necessary for the correct establishment of TJ in corneal epithelia and as well as the regulation of both the barrier function of TJ and its ability to respond to EGF. J. Cell. Physiol. 232: 1794-1807, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Molecular Evidence and Functional Expression of a Novel Drug Efflux pump (ABCC2) in Human Corneal Epithelium and Rabbit Cornea and its role in Ocular drug efflux

PubMed Central

Karla, Pradeep K.; Pal, Dhananjay; Quinn, Tim; Mitra, Ashim K.

2007-01-01

Cornea is considered as a major barrier for ocular drug delivery. Low ocular bioavailability of drugs has been attributed primarily to low permeability across corneal epithelium thus leading to sub-therapeutic concentrations of drug in the eye and treatment failure. The role of drug efflux proteins, particularly the Pglycoprotein in ocular drug bioavailability has been reported. The objective of this research was to determine whether human corneal epithelium expresses multi drug resistance associated proteins contributing to drug efflux by employing both cultured corneal cells and freshly excised rabbit cornea. SV40 HCEC and rPCEC were selected for in-vitro testing. SV40-HCEC and freshly excised rabbit corneas were utilized for transport studies. [3H]-cyclosporine-A and [14C]-erythromycin which are known substrates for ABCC2 and MK-571, a specific inhibitor for MRP were applied in this study. RT-PCR indicated a unique and distinct band at ∼272 bp corresponding to ABCC2 in HCEC, SV40-HCEC, rabbit cornea, rPCEC and MDCKII-MRP2 cells. Also RT-PCR indicated a unique band ∼181 bp for HCEC and SV40-HCEC. Immunoprecipitation followed by Western Blot analysis revealed a specific band at ∼190-kDa in membrane fraction of SV40-HCEC, MDCKII-MRP2 and no band with isotype control. Uptake of [3H]-cyclosporine-A and [14C]-erythromycin in the presence of MK-571 was significantly enhanced than control in both SV40 HCEC and rPCEC. Similarly a significant elevation in (A→B) permeability of [3H]-cyclosporine-A and [14C]-erythromycin was observed in the presence of MK-571 in SV40-HCEC. A→B transport of [3H]-cyclosporine-A was elevated in the presence of MK-571 in freshly excised rabbit cornea indicating potential role of this efflux transporter and high clinical significance of this finding. PMID:17156953

Corneal markers of diabetic neuropathy.

PubMed

Pritchard, Nicola; Edwards, Katie; Shahidi, Ayda M; Sampson, Geoff P; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan

2011-01-01

Diabetic neuropathy is a significant clinical problem that currently has no effective therapy, and in advanced cases, leads to foot ulceration and lower limb amputation. The accurate detection, characterization and quantification of this condition are important in order to define at-risk patients, anticipate deterioration, monitor progression, and assess new therapies. This review evaluates novel corneal methods of assessing diabetic neuropathy. Two new noninvasive corneal markers have emerged, and in cross-sectional studies have demonstrated their ability to stratify the severity of this disease. Corneal confocal microscopy allows quantification of corneal nerve parameters and noncontact corneal esthesiometry, the functional correlate of corneal structure, assesses the sensitivity of the cornea. Both these techniques are quick to perform, produce little or no discomfort for the patient, and are suitable for clinical settings. Each has advantages and disadvantages over traditional techniques for assessing diabetic neuropathy. Application of these new corneal markers for longitudinal evaluation of diabetic neuropathy has the potential to reduce dependence on more invasive, costly, and time-consuming assessments, such as skin biopsy.

Ciliary neurotrophic factor promotes the activation of corneal epithelial stem/progenitor cells and accelerates corneal epithelial wound healing.

PubMed

Zhou, Qingjun; Chen, Peng; Di, Guohu; Zhang, Yangyang; Wang, Yao; Qi, Xia; Duan, Haoyun; Xie, Lixin

2015-05-01

Ciliary neurotrophic factor (CNTF), a well-known neuroprotective cytokine, has been found to play an important role in neurogenesis and functional regulations of neural stem cells. As one of the most innervated tissue, however, the role of CNTF in cornea epithelium remains unclear. This study was to explore the roles and mechanisms of CNTF in the activation of corneal epithelial stem/progenitor cells and wound healing of both normal and diabetic mouse corneal epithelium. In mice subjecting to mechanical removal of corneal epithelium, the corneal epithelial stem/progenitor cell activation and wound healing were promoted by exogenous CNTF application, while delayed by CNTF neutralizing antibody. In cultured corneal epithelial stem/progenitor cells, CNTF enhanced the colony-forming efficiency, stimulated the mitogenic proliferation, and upregulated the expression levels of corneal epithelial stem/progenitor cell-associated transcription factors. Furthermore, the promotion of CNTF on the corneal epithelial stem/progenitor cell activation and wound healing was mediated by the activation of STAT3. Moreover, in diabetic mice, the content of CNTF in corneal epithelium decreased significantly when compared with that of normal mice, and the supplement of CNTF promoted the diabetic corneal epithelial wound healing, accompanied with the advanced activation of corneal epithelial stem/progenitor cells and the regeneration of corneal nerve fibers. Thus, the capability of expanding corneal epithelial stem/progenitor cells and promoting corneal epithelial wound healing and nerve regeneration indicates the potential application of CNTF in ameliorating limbal stem cell deficiency and treating diabetic keratopathy. © 2014 AlphaMed Press.

The management of corneal trauma: advances in the past twenty-five years.

PubMed

Macsai, M S

2000-09-01

Over the past quarter century, advances in our understanding of corneal anatomy, physiology, and wound healing have all played an integral role in the management of corneal trauma. As the etiologies of corneal trauma have changed, so has our understanding of the impact of injury on corneal function as it relates to visual rehabilitation. Numerous new classes of antibiotics, antiinflammatory agents, and tissue adhesives have emerged. Occlusive therapy has advanced from simple pressure patching bandage soft contact lenses and collagen shields. Surgical instrumentation, operating microscopes, viscoelastic substances, and suture materials have all improved the outcomes of corneal trauma repair. Improved understanding of the refractive properties of the cornea through topography and alternative suture techniques has helped us restore the natural corneal curvature and visual outcomes. Consequently, in the last quarter of this century our therapeutic approaches to cornea trauma, both medical and surgical, have improved.

Population-based assessment of vision-related quality of life in corneal disease: results from the CORE study.

PubMed

Vashist, Praveen; Gupta, Noopur; Tandon, Radhika; Gupta, Sanjeev K; Dwivedi, Sadanand; Mani, Kalaivani

2016-05-01

To assess the impact of corneal disease on vision-related quality of life (VR-QoL) in a rural North Indian population. Cross-sectional, population-based study. The Corneal Opacity Rural Epidemiological (CORE) study included 12 899 participants from 25 randomly selected clusters of rural Gurgaon, Haryana, India, with the primary objective of determining the prevalence of corneal disease in the general population during July 2011 to January 2013. VR-QoL was assessed through Indian Vision Function questionnaire (IND-VFQ-33) in adult participants (aged ≥18 years) detected with corneal opacity and equal number of healthy controls (no ocular pathology with visual acuity of 6/6 binocularly) selected from the same clusters. Scores of the three subscales of IND-VFQ-33 (vision-specific mobility, psychosocial impact and visual symptoms) were computed, analysed and compared separately across various groups. Overall, 12 113 participants of all ages underwent detailed ophthalmic examination and VR-QoL was assessed in 435 cases with corneal disease and 435 controls without any ophthalmic disease. The diseased population had significantly higher scores and hence poorer VR-QoL across all three domains of vision function (scores of 28 vs 22; 6 vs 5 and 14 vs 9, respectively; p<0.0001) and the scores were inversely related with the level of visual impairment in patients with corneal disease. Patients with unilateral corneal disease also had poorer VR-QoL scores as compared with healthy controls (p<0.0001). VR-QoL is impaired in patients with corneal disease, more so in patients with corneal blindness. This is the first population-based study to document VR-QoL through IND-VFQ-33 in the Indian population with corneal disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Human stem cell based corneal tissue mimicking structures using laser-assisted 3D bioprinting and functional bioinks.

PubMed

Sorkio, Anni; Koch, Lothar; Koivusalo, Laura; Deiwick, Andrea; Miettinen, Susanna; Chichkov, Boris; Skottman, Heli

2018-07-01

There is a high demand for developing methods to produce more native-like 3D corneal structures. In the present study, we produced 3D cornea-mimicking tissues using human stem cells and laser-assisted bioprinting (LaBP). Human embryonic stem cell derived limbal epithelial stem cells (hESC-LESC) were used as a cell source for printing epithelium-mimicking structures, whereas human adipose tissue derived stem cells (hASCs) were used for constructing layered stroma-mimicking structures. The development and optimization of functional bioinks was a crucial step towards successful bioprinting of 3D corneal structures. Recombinant human laminin and human sourced collagen I served as the bases for the functional bioinks. We used two previously established LaBP setups based on laser induced forward transfer, with different laser wavelengths and appropriate absorption layers. We bioprinted three types of corneal structures: stratified corneal epithelium using hESC-LESCs, lamellar corneal stroma using alternating acellular layers of bioink and layers with hASCs, and finally structures with both a stromal and epithelial part. The printed constructs were evaluated for their microstructure, cell viability and proliferation, and key protein expression (Ki67, p63α, p40, CK3, CK15, collagen type I, VWF). The 3D printed stromal constructs were also implanted into porcine corneal organ cultures. Both cell types maintained good viability after printing. Laser-printed hESC-LESCs showed epithelial cell morphology, expression of Ki67 proliferation marker and co-expression of corneal progenitor markers p63α and p40. Importantly, the printed hESC-LESCs formed a stratified epithelium with apical expression of CK3 and basal expression of the progenitor markers. The structure of the 3D bioprinted stroma demonstrated that the hASCs had organized horizontally as in the native corneal stroma and showed positive labeling for collagen I. After 7 days in porcine organ cultures, the 3D bioprinted stromal structures attached to the host tissue with signs of hASCs migration from the printed structure. This is the first study to demonstrate the feasibility of 3D LaBP for corneal applications using human stem cells and successful fabrication of layered 3D bioprinted tissues mimicking the structure of the native corneal tissue. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

In Vivo Confocal Microscopy of Corneal Nerves in Health and Disease

PubMed Central

Cruzat, Andrea; Qazi, Yureeda; Hamrah, Pedram

2016-01-01

In vivo confocal microscopy (IVCM) is becoming an indispensable tool for studying corneal physiology and disease. Enabling the dissection of corneal architecture at a cellular level, this technique offers fast and noninvasive in vivo imaging of the cornea with images comparable to that of ex vivo histochemical techniques. Corneal nerves bear substantial relevance to clinicians and scientists alike, given their pivotal roles in regulation of corneal sensation, maintenance of epithelial integrity, and proliferation and promotion of wound healing. Thus, IVCM offers a unique method to study corneal nerve alterations in a myriad of conditions, such as ocular and systemic diseases and following corneal surgery, without altering the tissue microenvironment. Of particular interest has been the correlation of corneal subbasal nerves to their function, which has been studied in normal eyes, contact lens wearers, and patients with keratoconus, infectious keratitis, corneal dystrophies, and neurotrophic keratopathy. Longitudinal studies have applied IVCM to investigate the effects of corneal surgery on nerves, demonstrating their regenerative capacity. IVCM is increasingly important in the diagnosis and management of systemic conditions such as peripheral diabetic neuropathy and, more recently, in ocular diseases. In this review, we outline the principles and applications of IVCM in the study of corneal nerves in various ocular and systemic diseases. PMID:27771327

Four-year follow-up of corneal aberrations and visual functions of myopic patients after laser in situ keratomileusis

PubMed Central

Liu, Tai-Xiang; Chen, Yong-Tao; Dan, Ting-Ting; Shi, Rong; Linghu, Shao-Rong; Li, Hai-Xiang

2015-01-01

Objective: To report on 4-year follow-up of corneal higher-order aberrations and daily visual functions of myopic patients after laser in situ keratomileusis (LASIK). Methods: One hundred thirty four eyes of 67 patients who underwent LASIK guided by aspherical ablation were included in this study. The vision, corneal spherical aberration (SphA) and Coma were recorded before LASIK and at 6 month and 4 year after LASIK. The evaluation of the questionnaire about daily visual functions was performed by the same physician after LASIK. Results: No eye decreased the BCVA during 4 year follow-up. The effect index and safety index were 1.08±0.16, 1.11±0.17 and 1.12±0.16, 1.13±0.14 respectively at 6 month and 4 year post-LASIK. After LASIK the corneal SphA and Coma were significantly increased, however the difference between 6 month and 4 year post-LASIK was no statistical significance. Most patients (94.3%-92.4%) felt satisfaction or high satisfaction about the ability to perform each daily visual function after LASIK. Meanwhile there was still about 7.4%-9.2% patients who complained that they could not drive at night. Further analysis showed that the score of driving at night was negative correlation with corneal SphA (r=-0.645, p=0.040; r=-0.688, p=0.040 at 6 month and 4 year post-LASIK respectively). Conclusions: Our four-year follow-up outcomes indicated that the myopic patients after LASIK had the long-term stable corneal aberration and satisfaction of daily visual functions. PMID:26870114

Helicoidal multi-lamellar features of RGD-functionalized silk biomaterials for corneal tissue engineering.

PubMed

Gil, Eun Seok; Mandal, Biman B; Park, Sang-Hyug; Marchant, Jeffrey K; Omenetto, Fiorenzo G; Kaplan, David L

2010-12-01

RGD-coupled silk protein-biomaterial lamellar systems were prepared and studied with human cornea fibroblasts (hCFs) to match functional requirements. A strategy for corneal tissue engineering was pursued to replicate the structural hierarchy of human corneal stroma within thin stacks of lamellae-like tissues, in this case constructed from scaffolds constructed with RGD-coupled, patterned, porous, mechanically robust and transparent silk films. The influence of RGD-coupling on the orientation, proliferation, ECM organization, and gene expression of hCFs was assessed. RGD surface modification enhanced cell attachment, proliferation, alignment and expression of both collagens (type I and V) and proteoglycans (decorin and biglycan). Confocal and histological images of the lamellar systems revealed that the bio-functionalized silk human cornea 3D constructs exhibited integrated corneal stroma tissue with helicoidal multi-lamellar alignment of collagen-rich and proteoglycan-rich extracellular matrix, with transparency of the construct. This biomimetic approach to replicate corneal stromal tissue structural hierarchy and architecture demonstrates a useful strategy for engineering human cornea. Further, this approach can be exploited for other tissue systems due to the pervasive nature of such helicoids in most human tissues. Copyright © 2010 Elsevier Ltd. All rights reserved.

Corneal Re-innervation and Sensation Recovery in Patients with Herpes Zoster Ophthalmicus: An In Vivo and Ex Vivo Study of Corneal Nerves

PubMed Central

Cruzat, Andrea; Hamrah, Pedram; Cavalcanti, Bernardo M.; Zheng, Lixin; Colby, Kathryn; Pavan-Langston, Deborah

2016-01-01

Purpose To study corneal reinnervation and sensation recovery in Herpes zoster Ophthalmicus (HZO). Methods Two patients with HZO were studied over time with serial corneal esthesiometry and laser in vivo confocal microscopy (IVCM). A Boston keratoprosthesis (B-KPro) type 1 was implanted and the explanted corneal tissues were examined by immunofluorescence histochemistry for βIII-tubulin to stain for corneal nerves. Results The initial central corneal IVCM performed in each patient, showed a complete lack of the subbasal nerve plexus, which was in accordance with severe loss of sensation (0 of 6 cm) measured by esthesiometry. When IVCM was repeated 2 years later prior to undergoing surgery, Case 1 showed a persistent lack of central subbasal nerves and sensation (0 of 6). In contrast, Case 2 showed regeneration of the central subbasal nerves (4,786 µm/mm2) with partial recovery of corneal sensation (2.5 of 6 cm). Immunostaining of the explanted corneal button in Case 1 showed no corneal nerves while Case 2, showed central and peripheral corneal nerves. Eight months after surgery, IVCM was again repeated in the donor tissue around the B-KPro in both patients, to study innervation of the corneal transplant. Case 1 showed no nerves, while Case 2 showed new nerves growing from the periphery into the corneal graft. Conclusions We demonstrate that regaining corneal innervation and function is possible in patients with HZO as shown by corneal sensation, IVCM, and ex-vivo immunostaining, indicating zoster neural damage is not always permanent and it may recover over an extended period of time. PMID:26989956

Corneal biomechanical properties from air-puff corneal deformation imaging

NASA Astrophysics Data System (ADS)

Marcos, Susana; Kling, Sabine; Bekesi, Nandor; Dorronsoro, Carlos

2014-02-01

The combination of air-puff systems with real-time corneal imaging (i.e. Optical Coherence Tomography (OCT), or Scheimpflug) is a promising approach to assess the dynamic biomechanical properties of the corneal tissue in vivo. In this study we present an experimental system which, together with finite element modeling, allows measurements of corneal biomechanical properties from corneal deformation imaging, both ex vivo and in vivo. A spectral OCT instrument combined with an air puff from a non-contact tonometer in a non-collinear configuration was used to image the corneal deformation over full corneal cross-sections, as well as to obtain high speed measurements of the temporal deformation of the corneal apex. Quantitative analysis allows direct extraction of several deformation parameters, such as apex indentation across time, maximal indentation depth, temporal symmetry and peak distance at maximal deformation. The potential of the technique is demonstrated and compared to air-puff imaging with Scheimpflug. Measurements ex vivo were performed on 14 freshly enucleated porcine eyes and five human donor eyes. Measurements in vivo were performed on nine human eyes. Corneal deformation was studied as a function of Intraocular Pressure (IOP, 15-45 mmHg), dehydration, changes in corneal rigidity (produced by UV corneal cross-linking, CXL), and different boundary conditions (sclera, ocular muscles). Geometrical deformation parameters were used as input for inverse finite element simulation to retrieve the corneal dynamic elastic and viscoelastic parameters. Temporal and spatial deformation profiles were very sensitive to the IOP. CXL produced a significant reduction of the cornea indentation (1.41x), and a change in the temporal symmetry of the corneal deformation profile (1.65x), indicating a change in the viscoelastic properties with treatment. Combining air-puff with dynamic imaging and finite element modeling allows characterizing the corneal biomechanics in-vivo.

Why Does the Healthy Cornea Resist Pseudomonas aeruginosa Infection?

PubMed Central

Evans, David J.; Fleiszig, Suzanne M. J.

2013-01-01

Purpose To provide our perspective on why the cornea is resistant to infection based on our research results with Pseudomonas aeruginosa. Perspective We focus on our current understanding of the interplay between bacteria, tear fluid and the corneal epithelium that determine health as the usual outcome, and propose a theoretical model for how contact lens wear might change those interactions to enable susceptibility to P. aeruginosa infection. Methods Use of “null-infection” in vivo models, cultured human corneal epithelial cells, contact lens-wearing animal models, and bacterial genetics help to elucidate mechanisms by which P. aeruginosa survive at the ocular surface, adheres, and traverses multilayered corneal epithelia. These models also help elucidate the molecular mechanisms of corneal epithelial innate defense. Results and Discussion Tear fluid and the corneal epithelium combine to make a formidable defense against P. aeruginosa infection of the cornea. Part of that defense involves the expression of antimicrobials such as β-defensins, the cathelicidin LL-37, cytokeratin-derived antimicrobial peptides, and RNase7. Immunomodulators such as SP-D and ST2 also contribute. Innate defenses of the cornea depend in part on MyD88, a key adaptor protein of TLR and IL-1R signaling, but the basal lamina represents the final barrier to bacterial penetration. Overcoming these defenses involves P. aeruginosa adaptation, expression of the type three secretion system, proteases, and P. aeruginosa biofilm formation on contact lenses. Conclusion After more than two decades of research focused on understanding how contact lens wear predisposes to P. aeruginosa infection, our working hypothesis places blame for microbial keratitis on bacterial adaptation to ocular surface defenses, combined with changes to the biochemistry of the corneal surface caused by trapping bacteria and tear fluid against the cornea under the lens. PMID:23601656

Resolvin E1 (RX-10001) reduces corneal epithelial barrier disruption and protects against goblet cell loss in a murine model of dry eye.

PubMed

de Paiva, Cintia S; Schwartz, C Eric; Gjörstrup, Per; Pflugfelder, Stephen C

2012-11-01

Resolvin E1 (RvE1; RX-10001) belongs to a new class of endogenous immunoregulating mediators, originally identified as a metabolite of the omega-3 polyunsaturated fatty acid, eicosapentaenoic acid. Based on its proven efficacy in models of chronic inflammation, this study investigated the efficacy of resolvin E1 in a murine model of dry eye. C57/B6 mice, aged 6 to 8 weeks, were treated with systemic scopolamine and exposed to air draft and low humidity for 16 hours/day for 5 days and allocated to the following groups: unexposed controls, disease controls, treatment with vehicle or RvE1 delivered topically as its methyl ester prodrug, RX-10005, to enhance corneal surface penetration. Treatment was initiated at the time of desiccating stress induction. Treatment efficacy was assessed by corneal permeability using Oregon Green Dextran and by conjunctival goblet cell density using periodic acid-Schiff reagent. RvE1 reduced the increase in corneal staining by 80% compared with untreated disease controls. Goblet cell density was reduced by 20% in disease controls but fully maintained in the group receiving RvE1. RvE1, delivered as its methyl ester prodrug, improved the outcome measures of corneal staining and goblet cell density in this murine model of dry eye, indicating the potential utility of endogenous resolvins and resolvin analogues in the treatment of dry eye.

LRIG1 inhibits STAT3-dependent inflammation to maintain corneal homeostasis

PubMed Central

Nakamura, Takahiro; Hamuro, Junji; Takaishi, Mikiro; Simmons, Szandor; Maruyama, Kazuichi; Zaffalon, Andrea; Bentley, Adam J.; Kawasaki, Satoshi; Nagata-Takaoka, Maho; Fullwood, Nigel J.; Itami, Satoshi; Sano, Shigetoshi; Ishii, Masaru; Barrandon, Yann; Kinoshita, Shigeru

2013-01-01

Corneal integrity and transparency are indispensable for good vision. Cornea homeostasis is entirely dependent upon corneal stem cells, which are required for complex wound-healing processes that restore corneal integrity following epithelial damage. Here, we found that leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is highly expressed in the human holoclone-type corneal epithelial stem cell population and sporadically expressed in the basal cells of ocular-surface epithelium. In murine models, LRIG1 regulated corneal epithelial cell fate during wound repair. Deletion of Lrig1 resulted in impaired stem cell recruitment following injury and promoted a cell-fate switch from transparent epithelium to keratinized skin-like epidermis, which led to corneal blindness. In addition, we determined that LRIG1 is a negative regulator of the STAT3-dependent inflammatory pathway. Inhibition of STAT3 in corneas of Lrig1–/– mice rescued pathological phenotypes and prevented corneal opacity. Additionally, transgenic mice that expressed a constitutively active form of STAT3 in the corneal epithelium had abnormal features, including corneal plaques and neovascularization similar to that found in Lrig1–/– mice. Bone marrow chimera experiments indicated that LRIG1 also coordinates the function of bone marrow–derived inflammatory cells. Together, our data indicate that LRIG1 orchestrates corneal-tissue transparency and cell fate during repair, and identify LRIG1 as a key regulator of tissue homeostasis. PMID:24316976

Impact of donor health on corneal biochemistry--an unexpected caveat from a pilot study.

PubMed

Kryczka, Tomasz; Chrapusta, Stanisław J; Szaflik, Jacek P; Szaflik, Jerzy; Midelfart, Anna

2014-03-12

To test the possibility that some chronic systemic maladies not directly related to the function of the eye may significantly and permanently disturb corneal metabolism. Contents of selected low molecular weight metabolites were compared among corneas collected from donors who died suddenly of an accident or non-poisoning suicide, or met a sudden non-accidental death from unidentified causes, or died of a chronic cardiovascular disease or of idiopathic liver cirrhosis (N=4 for each group). Corneal buttons were halved; one half was snap-frozen and stored at -80°C, and the other half was stored at +4°C in Eusol-C for 8 days and then was snap-frozen and stored at -80°C until analyzed. Metabolite contents were assessed using high-resolution magic angle spinning proton NMR spectroscopy. Significant between-group differences in corneal biochemical profiles were identified. Most of them were reduced or nullified by the Eusol-C storage, suggesting their link to differences in in vivo corneal environment. The corneas from donors with liver cirrhosis or cardiovascular diseases differed considerably from the remaining ones, both before and after the Eusol-C storage. Various chronic systemic diseases that are not directly related to the function of the eye markedly affect corneal biochemistry. Some of the alterations are likely related to a permanent aberration in corneal metabolism. A study is warranted in larger donor groups on the effect of idiopathic liver cirrhosis and cardiovascular diseases on corneal metabolism and/or a retrospective analysis of the long-term outcome of keratoplasty and other grafting procedures employing materials from these donor groups.

Hyperosmolar Tears Induce Functional and Structural Alterations of Corneal Nerves: Electrophysiological and Anatomical Evidence Toward Neurotoxicity

PubMed Central

Hirata, Harumitsu; Mizerska, Kamila; Marfurt, Carl F.; Rosenblatt, Mark I.

2015-01-01

Purpose In an effort to elucidate possible neural mechanisms underlying diminished tearing in dry eye disease, this study sought to determine if hyperosmolar tears, a ubiquitous sign of dry eye disease, produce functional changes in corneal nerve responses to drying of the cornea and if these changes correlate with alterations in corneal nerve morphology. Methods In vivo extracellular electrophysiological recordings were performed in rat trigeminal ganglion neurons that innervated the cornea before, and up to 3 hours after, the ocular application of continuous hyperosmolar tears or artificial tears. In corollary experiments, immunohistochemical staining was performed to compare corneal nerve morphology in control and in eyes treated with hyperosmolar solutions. Results Our previous studies identified a population of corneal afferents, dry-sensitive neurons that are strongly excited by corneal dessication (“dry response”), a response thought to trigger the lacrimation reflex. In the present study, we found that the dry responses of corneal dry-sensitive neurons were depressed or even completely abolished by hyperosmolar tears in a time- (30 minutes to 3 hours) and dose (450- to 1000-mOsm solutions)-dependent manner. Furthermore, eyes treated with hyperosmolar tears for 3 hours contained large numbers of morphologically abnormal (granular, fragmented, or prominently beaded) subbasal nerves that appeared to be undergoing degeneration. Conclusions These results demonstrate that tear hyperosmolarity, considered to be a “core” mechanism of dry eye disease, significantly decreases physiological sensitivity and morphologic integrity of the corneal nerves important in tear production. These alterations might contribute to the diminished tearing seen clinically in dry eye patients. PMID:26720465

Hyperosmolar Tears Induce Functional and Structural Alterations of Corneal Nerves: Electrophysiological and Anatomical Evidence Toward Neurotoxicity.

PubMed

Hirata, Harumitsu; Mizerska, Kamila; Marfurt, Carl F; Rosenblatt, Mark I

2015-12-01

In an effort to elucidate possible neural mechanisms underlying diminished tearing in dry eye disease, this study sought to determine if hyperosmolar tears, a ubiquitous sign of dry eye disease, produce functional changes in corneal nerve responses to drying of the cornea and if these changes correlate with alterations in corneal nerve morphology. In vivo extracellular electrophysiological recordings were performed in rat trigeminal ganglion neurons that innervated the cornea before, and up to 3 hours after, the ocular application of continuous hyperosmolar tears or artificial tears. In corollary experiments, immunohistochemical staining was performed to compare corneal nerve morphology in control and in eyes treated with hyperosmolar solutions. Our previous studies identified a population of corneal afferents, dry-sensitive neurons that are strongly excited by corneal dessication ("dry response"), a response thought to trigger the lacrimation reflex. In the present study, we found that the dry responses of corneal dry-sensitive neurons were depressed or even completely abolished by hyperosmolar tears in a time- (30 minutes to 3 hours) and dose (450- to 1000-mOsm solutions)-dependent manner. Furthermore, eyes treated with hyperosmolar tears for 3 hours contained large numbers of morphologically abnormal (granular, fragmented, or prominently beaded) subbasal nerves that appeared to be undergoing degeneration. These results demonstrate that tear hyperosmolarity, considered to be a "core" mechanism of dry eye disease, significantly decreases physiological sensitivity and morphologic integrity of the corneal nerves important in tear production. These alterations might contribute to the diminished tearing seen clinically in dry eye patients.

Differential localization of vesicular glutamate transporters and peptides in corneal afferents to trigeminal nucleus caudalis.

PubMed

Hegarty, Deborah M; Tonsfeldt, Karen; Hermes, Sam M; Helfand, Helen; Aicher, Sue A

2010-09-01

Trigeminal afferents convey nociceptive information from the corneal surface of the eye to the trigeminal subnucleus caudalis (Vc). Trigeminal afferents, like other nociceptors, are thought to use glutamate and neuropeptides as neurotransmitters. The current studies examined whether corneal afferents contain both neuropeptides and vesicular glutamate transporters. Corneal afferents to the Vc were identified by using cholera toxin B (CTb). Corneal afferents project in two clusters to the rostral and caudal borders of the Vc, regions that contain functionally distinct nociceptive neurons. Thus, corneal afferents projecting to these two regions were examined separately. Dual immunocytochemical studies combined CTb with either calcitonin gene-related peptide (CGRP), substance P (SP), vesicular glutamate transporter 1 (VGluT1), or VGluT2. Corneal afferents were more likely to contain CGRP than SP, and corneal afferents projecting to the rostral region were more likely to contain CGRP than afferents projecting caudally. Overall, corneal afferents were equally likely to contain VGluT1 or VGluT2. Together, 61% of corneal afferents contained either VGluT1 or VGluT2, suggesting that some afferents lack a VGluT. Caudal corneal afferents were more likely to contain VGluT2 than VGluT1, whereas rostral corneal afferents were more likely to contain VGluT1 than VGluT2. Triple-labeling studies combining CTb, CGRP, and VGluT2 showed that very few corneal afferents contain both CGRP and VGluT2, caudally (1%) and rostrally (2%). These results suggest that most corneal afferents contain a peptide or a VGluT, but rarely both. Our results are consistent with a growing literature suggesting that glutamatergic and peptidergic sensory afferents may be distinct populations.

Stromal Tissue Rigidity Promotes Mesenchymal Stem Cell-Mediated Corneal Wound Healing Through the Transforming Growth Factor β Signaling Pathway.

PubMed

Yang, Yun-Hsiang; Hsieh, Ting-Lieh; Ji, Andrea Tung-Qian; Hsu, Wei-Tse; Liu, Chia-Yu; Lee, Oscar Kuang-Sheng; Ho, Jennifer Hui-Chun

2016-10-01

The healing of a corneal epithelial defect is essential for preventing infectious corneal ulcers and subsequent blindness. We previously demonstrated that mesenchymal stem cells (MSCs) in the corneal stroma, through a paracrine mechanism, yield a more favorable therapeutic benefit for corneal wound re-epithelialization than do MSCs in the corneal epithelium. In this study, MSCs were grown on a matrix with the rigidity of the physiological human vitreous (1 kPa), corneal epithelium (8 kPa), or corneal stroma (25 kPa) for investigating the role of corneal tissue rigidity in MSC functions regarding re-epithelialization promotion. MSC growth on a 25-kPa dish significantly promoted the wound healing of human corneal epithelial (HCE-T) cells. Among growth factors contributing to corneal epithelial wound healing, corneal stromal rigidity selectively enhanced transforming growth factor-beta (TGF-β) secretion from MSCs. Inhibitors of TGF-β pan receptor, TGF-β receptor 1, and Smad2 dose dependently abrogated MSC-mediated HCE-T wound healing. Furthermore, MSCs growth on a matrix with corneal stromal rigidity enhanced the ability of themselves to promote corneal re-epithelialization by activating matrix metalloproteinase (MMP) expression and integrin β1 production in HCE-T cells through TGF-β signaling pathway activation. Smad2 activation resulted in the upregulation of MMP-2 and -13 expression in HCE-T cells, whereas integrin β1 production favored a Smad2-independent TGF-β pathway. Altogether, we conclude that corneal stromal rigidity is a critical factor for MSC-induced promotion of corneal re-epithelialization. The activation of the TGF-β signaling pathway, which maintains the balance between integrin and MMP expression, in HCE-T cells is the major pathway responsible for MSC-mediated wound healing. Stem Cells 2016;34:2525-2535. © 2016 AlphaMed Press.

Restoration of Corneal Transparency by Mesenchymal Stem Cells.

PubMed

Mittal, Sharad K; Omoto, Masahiro; Amouzegar, Afsaneh; Sahu, Anuradha; Rezazadeh, Alexandra; Katikireddy, Kishore R; Shah, Dhvanit I; Sahu, Srikant K; Chauhan, Sunil K

2016-10-11

Transparency of the cornea is indispensable for optimal vision. Ocular trauma is a leading cause of corneal opacity, leading to 25 million cases of blindness annually. Recently, mesenchymal stem cells (MSCs) have gained prominence due to their inflammation-suppressing and tissue repair functions. Here, we investigate the potential of MSCs to restore corneal transparency following ocular injury. Using an in vivo mouse model of ocular injury, we report that MSCs have the capacity to restore corneal transparency by secreting high levels of hepatocyte growth factor (HGF). Interestingly, our data also show that HGF alone can restore corneal transparency, an observation that has translational implications for the development of HGF-based therapy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

New therapeutic approaches in the treatment of diabetic keratopathy: a review.

PubMed

Abdelkader, Hamdy; Patel, Dipika V; McGhee, Charles Nj; Alany, Raid G

2011-04-01

The cornea is densely innervated, and the integrity of these nerve fibres is critical in maintaining the refractive and protective functions of the cornea. Many ocular and systemic diseases can adversely affect corneal sensory nerves and consequently impair their function, with vision loss being the inevitable consequence of severe corneal neurotrophic ulceration. However, current standard treatments regimens are often ineffective. Over the past three decades, the role of growth factors in maintaining the normal structure and function of the cornea, and in corneal epithelial healing, has become increasingly evident. Many preclinical and clinical trials have shown that growth factors and cytokines can significantly enhance epithelialization (epithelial proliferation and migration) and consequently accelerate wound healing. More recently, local/topical administration of insulin, naltrexone (opioid antagonist) and nicergoline (ergoline derivatives) were found to improve, and significantly increase, the corneal wound healing rate. This report reviews the major attributes of these growth factors and therapeutic agents that may be used in ameliorating impaired corneal wound healing, and presents a perspective on the potential clinical use of these agents as a new generation of ophthalmic pharmaceuticals for the treatment of diabetic keratopathy. © 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists.

Interocular high-order corneal wavefront aberration symmetry

NASA Astrophysics Data System (ADS)

Lombardo, Marco; Lombardo, Giuseppe; Serrao, Sebastiano

2006-04-01

The interocular symmetry of the high-order corneal wavefront aberration (WA) in a population of myopic eyes was analyzed before and after photorefractive keratectomy (PRK). The preoperative and one-year postoperative corneal aberration data (from third to seventh Zernike orders) for 4- and 7-mm pupils from right and left eyes were averaged after correcting for the effects of enantiomorphism to test for mirror symmetry. Also, the mean corneal point-spread function (PSF) for right and left eyes was calculated. Preoperatively, a moderate and high degree of correlation in the high-order corneal WA between eyes was found for 4- and 7-mm pupils, respectively. Myopic PRK did not significantly change the interocular symmetry of corneal high-order aberrations. No discernible differences in the orientation PSF between eyes were observed one year after surgery in comparison with the preoperative state over the two analyzed pupils.

Corona sign: manifestation of peripheral corneal epithelial edema as a possible marker of the progression of corneal endothelial dysfunction.

PubMed

Inoue, Tomoyuki; Hara, Yuko; Kobayashi, Takeshi; Zheng, Xiaodong; Suzuki, Takashi; Shiraishi, Atsushi; Ohashi, Yuichi

2016-09-01

To describe a characteristic form of the corona sign and its clinical relevance to the degree of corneal endothelial decompensation and investigate the underlying mechanism using a rabbit model. These observational cases include 31 patients undergoing penetrating keratoplasty (PKP) and 15 patients undergoing Descemet stripping automated endothelial keratoplasty (DSAEK) with special attention to the circumferentially developed corneal epithelial edema. We also conducted a laboratory observation of horizontal water flow in the rabbit cornea. We consistently observed the corona sign at the superior periphery during the initial stage of corneal endothelial decompensation after PKP. With progressive corneal endothelial cellular loss, the epithelial edema gradually expanded circumferentially in the periphery. The endothelial cellular density associated with the corona sign significantly (P < 0.01) decreased compared with that without the sign. The endothelial cellular density decreased significantly (P < 0.05) in cases with a circumferential corona sign compared with a superior corona sign. After DSAEK, however, the corneal epithelial edema subsided from the center but persisted peripherally as a corona sign in all cases. By 3 months postoperatively, the epithelial edema was confined to the superior periphery along with uneventful corneal endothelial healing. Rabbit experiments showed that total corneal endothelial decompensation decreased the horizontal intracorneal water migration (Inoue-Ohashi phenomenon) in the corneal periphery and induced peripheral corneal edema. The slit-lamp microscopic findings of the corona-like epithelial edema in the peripheral cornea are associated with the stage of corneal endothelial function. To support this, the developmental mechanism of the corona sign was demonstrated experimentally.

THz and mm-Wave Sensing of Corneal Tissue Water Content: Electromagnetic Modeling and Analysis

PubMed Central

Taylor, Zachary D.; Garritano, James; Sung, Shijun; Bajwa, Neha; Bennett, David B.; Nowroozi, Bryan; Tewari, Priyamvada; Sayre, James; Hubschman, Jean-Pierre; Deng, Sophie; Brown, Elliott R.; Grundfest, Warren S.

2015-01-01

Terahertz (THz) spectral properties of human cornea are explored as a function of central corneal thickness (CCT) and corneal water content, and the clinical utility of THz-based corneal water content sensing is discussed. Three candidate corneal tissue water content (CTWC) perturbations, based on corneal physiology, are investigated that affect the axial water distribution and total thickness. The THz frequency reflectivity properties of the three CTWC perturbations were simulated and explored with varying system center frequency and bandwidths (Q-factors). The modeling showed that at effective optical path lengths on the order of a wavelength the cornea presents a lossy etalon bordered by air at the anterior and the aqueous humor at the posterior. The simulated standing wave peak-to-valley ratio is pronounced at lower frequencies and its effect on acquired data can be modulated by adjusting the bandwidth of the sensing system. These observations are supported with experimental spectroscopic data. The results suggest that a priori knowledge of corneal thickness can be utilized for accurate assessments of corneal tissue water content. The physiologic variation of corneal thickness with respect to the wavelengths spanned by the THz band is extremely limited compared to all other structures in the body making CTWC sensing unique amongst all proposed applications of THz medical imaging. PMID:26322247

Peroxynitrite Upregulates Angiogenic Factors VEGF-A, BFGF, and HIF-1α in Human Corneal Limbal Epithelial Cells

PubMed Central

Ashki, Negin; Chan, Ann M.; Qin, Yu; Wang, Wei; Kiyohara, Meagan; Lin, Lin; Braun, Jonathan; Wadehra, Madhuri; Gordon, Lynn K.

2014-01-01

Purpose. Corneal neovascularization (NV) is a sight-threatening condition often associated with infection, inflammation, prolonged contact lens use, corneal burns, and acute corneal graft rejection. Macrophages recruited to the cornea release nitric oxide (NO) and superoxide anion (O2−), which react together to form the highly toxic molecule peroxynitrite (ONOO−). The role of ONOO− in upregulating multiple angiogenic factors in cultured human corneal limbal epithelial (HCLE) cells was investigated. Methods. Human corneal limbal epithelial cells were incubated with 500 μM of ONOO− donor for various times. VEGF-A, BFGF, and hypoxic-inducible factor-alpha (HIF-1α) were investigated via Western blot and RT-PCR was performed for VEGF. Functional assays using human umbilical vein endothelial cells (HUVEC) used conditioned media from ONOO−-exposed HCLE cells. Secreted VEGF from conditioned media was detected and analyzed using ELISA. Results. Increased angiogenic factors were observed as early as 4 hours after HCLE exposure to ONOO−. HIF-1 expression was seen at 4, 6, and 8 hours post-ONOO− exposure (P < 0.05). BFGF expression was elevated at 4 hours and peaked at 8 hours after treatment with ONOO− (P < 0.005). Increased VEGF-A gene expression was observed at 6 and 8 hours post-ONOO− treatment. Functional assays using conditioned media showed increased HUVEC migration and tube formation. Conclusions. Exposure to elevated extracellular concentrations of ONOO− results in upregulation of angiogenic factors in HCLE cells. It is possible that, in the setting of inflammation or infection, that exposure to ONOO− could be one contributor to the complex initiators of corneal NV. Validation in vivo would identify an additional potential control point for corneal NV. PMID:24398102

Peroxynitrite upregulates angiogenic factors VEGF-A, BFGF, and HIF-1α in human corneal limbal epithelial cells.

PubMed

Ashki, Negin; Chan, Ann M; Qin, Yu; Wang, Wei; Kiyohara, Meagan; Lin, Lin; Braun, Jonathan; Wadehra, Madhuri; Gordon, Lynn K

2014-03-19

Corneal neovascularization (NV) is a sight-threatening condition often associated with infection, inflammation, prolonged contact lens use, corneal burns, and acute corneal graft rejection. Macrophages recruited to the cornea release nitric oxide (NO) and superoxide anion (O2(-)), which react together to form the highly toxic molecule peroxynitrite (ONOO(-)). The role of ONOO(-) in upregulating multiple angiogenic factors in cultured human corneal limbal epithelial (HCLE) cells was investigated. Human corneal limbal epithelial cells were incubated with 500 μM of ONOO(-) donor for various times. VEGF-A, BFGF, and hypoxic-inducible factor-alpha (HIF-1α) were investigated via Western blot and RT-PCR was performed for VEGF. Functional assays using human umbilical vein endothelial cells (HUVEC) used conditioned media from ONOO(-)-exposed HCLE cells. Secreted VEGF from conditioned media was detected and analyzed using ELISA. Increased angiogenic factors were observed as early as 4 hours after HCLE exposure to ONOO(-). HIF-1 expression was seen at 4, 6, and 8 hours post-ONOO(-) exposure (P < 0.05). BFGF expression was elevated at 4 hours and peaked at 8 hours after treatment with ONOO(-) (P < 0.005). Increased VEGF-A gene expression was observed at 6 and 8 hours post-ONOO(-) treatment. Functional assays using conditioned media showed increased HUVEC migration and tube formation. Exposure to elevated extracellular concentrations of ONOO(-) results in upregulation of angiogenic factors in HCLE cells. It is possible that, in the setting of inflammation or infection, that exposure to ONOO(-) could be one contributor to the complex initiators of corneal NV. Validation in vivo would identify an additional potential control point for corneal NV.

Corneal surface glycosylation is modulated by IL-1R and Pseudomonas aeruginosa challenge but is insufficient for inhibiting bacterial binding.

PubMed

Jolly, Amber L; Agarwal, Paresh; Metruccio, Matteo M E; Spiciarich, David R; Evans, David J; Bertozzi, Carolyn R; Fleiszig, Suzanne M J

2017-06-01

Cell surface glycosylation is thought to be involved in barrier function against microbes at mucosal surfaces. Previously we showed that the epithelium of healthy mouse corneas becomes vulnerable to Pseudomonas aeruginosa adhesion if it lacks the innate defense protein MyD88 (myeloid differentiation primary response gene 88), or after superficial injury by blotting with tissue paper. Here we explored their effect on corneal surface glycosylation using a metabolic label, tetra-acetylated N -azidoacetylgalactosamine (Ac 4 GalNAz). Ac 4 GalNAz treatment labeled the surface of healthy mouse corneas, leaving most cells viable, and bacteria preferentially associated with GalNAz-labeled regions. Surprisingly, corneas from MyD88 -/- mice displayed similar GalNAz labeling to wild-type corneas, but labeling was reduced and patchy on IL-1 receptor (IL-1R)-knockout mouse corneas ( P < 0.05, ANOVA). Tissue paper blotting removed GalNAz-labeled surface cells, causing DAPI labeling (permeabilization) of underlying cells. MS of material collected on the tissue paper blots revealed 67 GalNAz-labeled proteins, including intracellular proteins. These data show that the normal distribution of surface glycosylation requires IL-1R, but not MyD88, and is not sufficient to prevent bacterial binding. They also suggest increased P. aeruginosa adhesion to MyD88 -/- and blotted corneas is not due to reduction in total surface glycosylation, and for tissue paper blotting is likely due to cell permeabilization.-Jolly, A. L., Agarwal, P., Metruccio, M. M. E., Spiciarich, D. R., Evans, D. J., Bertozzi, C. R., Fleiszig, S. M. J. Corneal surface glycosylation is modulated by IL-1R and Pseudomonas aeruginosa challenge but is insufficient for inhibiting bacterial binding. © FASEB.

Corneal confocal microscopy alterations in Sjögren's syndrome dry eye.

PubMed

Lanza, Michele; Iaccarino, Stefania; Varricchi, Gilda; D'Errico, Tito; Gironi Carnevale, Ugo Antonello; Bifani, Mario

2017-08-01

To evaluate light backscattering (LB) in corneal layers in patients with primary Sjögren's syndrome dry eye (SSDE) utilizing in vivo corneal confocal microscopy (IVCM) and to determine the eventual association with the lacrimal functional test values. A complete ophthalmic evaluation, Schirmer test with and without stimulation, break-up time (BUT) and IVCM were performed on 55 patients affected by SSDE and in an age- and sex-matched cohort of healthy participants (HP). Light backscattering, measures as light reflectivity unit (LRU), detected by IVCM at Bowman's membrane (BM) at 50 μm, at 100 μm and at 200 μm deeper than BM was compared in the two groups. The correlations between LB values and lacrimal function results were evaluated. In patients affected by SSDE, LB was significantly higher (p < 0.001) in each corneal layer examined (+14 ± 6.33 LRU at BM), compared with HP. A good reverse correlation between the light reflectivity measures at BM with Schirmer test with (r = -0.91) and without (r = -0.90) stimulation and BUT (r = -0.88) was found. Correlations were lower in the deeper corneal layers. Even if our results should be confirmed in further studies with a larger population, these findings show that IVCM is a device able to detect alterations in corneal layers in SSDE patients related to the lacrimal function. Light backscattering (LB) could be very useful for clinical diagnosis and management of SSDE. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Function of the tryptophan metabolite, L-kynurenine, in human corneal endothelial cells

PubMed Central

Lahdou, Imad; Scheuerle, Alexander; Höftberger, Romana; Aboul-Enein, Fahmy

2009-01-01

Purpose Penetrating keratoplasty has been the mainstay for the treatment of blindness and is the most common form of tissue transplantation worldwide. Due to significant rates of rejection, treatment of immunological transplant reactions is of wide interest. Recently in a mouse model, the overexpression of indoeleamine 2,3 dioxigenase (IDO) was led to an extension in corneal allograft survival. L-kynurenine is a tryptophan metabolite, which may render activated T-cells apoptotic and therefore might modulate an allogenous transplant reaction. The function of L-kynurenine in the human cornea remains unclear. We analyzed the expression levels of IDO in human corneal endothelial cells (HCECs) and downstream tryptophan/kynurenine mechanisms in cell culture. Methods An immunological activation profile was determined in proliferation assays of monocytes from healthy donors. Reversed-phase high pressure liquid chromatography (HPLC), western blot, real time polymerase chain reaction (PCR), and microarray analyses were used. The expression of IDO and immunological infiltration of rejected human corneal allografts (n=12) were analyzed by immunohistochemistry. Results We found IDO and an associated tryptophan/kynurenine transporter protein exchange mechanism upregulated by inflammatory cytokines in HCECs. The inhibition of T-cell proliferation might depend on rapid delivery of the tryptophan metabolite, L-kynurenine, to the local corneal environment. Microarray analysis gives evidence that the large amino acid transporter 1 (LAT1) transporter protein is responsible for this mechanism. Conclusions Our data support that adequate levels of functional L-kynurenine might contribute to the maintenance of a relative immune privilege in the ocular anterior chamber, thereby contributing to the preservation of corneal allogeneic cells. PMID:19597571

Global Survey of Corneal Transplantation and Eye Banking.

PubMed

Gain, Philippe; Jullienne, Rémy; He, Zhiguo; Aldossary, Mansour; Acquart, Sophie; Cognasse, Fabrice; Thuret, Gilles

2016-02-01

Corneal transplantation restores visual function when visual impairment caused by a corneal disease becomes too severe. It is considered the world's most frequent type of transplantation, but, to our knowledge, there are no exhaustive data allowing measurement of supply and demand, although such data are essential in defining local, national, and global strategies to fight corneal blindness. To describe the worldwide situation of corneal transplantation supply and demand. Data were collected between August 2012 and August 2013 from a systematic review of published literature in parallel with national and international reports on corneal transplantation and eye banking. In a second step, eye bank staff and/or corneal surgeons were interviewed on their local activities. Interviews were performed during international ophthalmology or eye-banking congresses or by telephone or email. Countries' national supply/demand status was classified using a 7-grade system. Data were collected from 148 countries. Corneal transplantation and corneal procurements per capita in each country. In 2012, we identified 184,576 corneal transplants performed in 116 countries. These were procured from 283,530 corneas and stored in 742 eye banks. The top indications were Fuchs dystrophy (39% of all corneal transplants performed), a primary corneal edema mostly affecting elderly individuals; keratoconus (27%), a corneal disease that slowly deforms the cornea in young people; and sequellae of infectious keratitis (20%). The United States, with 199.10-6 corneal transplants per capita, had the highest transplantation rate, followed by Lebanon (122.10-6) and Canada (117.10-6), while the median of the 116 transplanting countries was 19.10-6. Corneas were procured in only 82 countries. Only the United States and Sri Lanka exported large numbers of donor corneas. About 53% of the world's population had no access to corneal transplantation. Our survey globally quantified the considerable shortage of corneal graft tissue, with only 1 cornea available for 70 needed. Efforts to encourage cornea donation must continue in all countries, but it is also essential to develop alternative and/or complementary solutions, such as corneal bioengineering.

Corneal blindness: a global perspective.

PubMed Central

Whitcher, J. P.; Srinivasan, M.; Upadhyay, M. P.

2001-01-01

Diseases affecting the cornea are a major cause of blindness worldwide, second only to cataract in overall importance. The epidemiology of corneal blindness is complicated and encompasses a wide variety of infectious and inflammatory eye diseses that cause corneal scarring, which ultimately leads to functional blindness. In addition, the prevalence of corneal disease varies from country to country and even from one population to another. While cataract is responsible for nearly 20 million of the 45 million blind people in the world, the next major cause is trachoma which blinds 4.9 million individuals, mainly as a result of corneal scarring and vascularization. Ocular trauma and corneal ulceration are significant causes of corneal blindness that are often underreported but may be responsible for 1.5-2.0 million new cases of monocular blindness every year. Causes of childhood blindness (about 1.5 million worldwide with 5 million visually disabled) include xerophthalmia (350,000 cases annually), ophthalmia neonatorum, and less frequently seen ocular diseases such as herpes simplex virus infections and vernal keratoconjunctivitis. Even though the control of onchocerciasis and leprosy are public health success stories, these diseases are still significant causes of blindness--affecting a quarter of a million individuals each. Traditional eye medicines have also been implicated as a major risk factor in the current epidemic of corneal ulceration in developing countries. Because of the difficulty of treating corneal blindness once it has occurred, public health prevention programmes are the most cost-effective means of decreasing the global burden of corneal blindness. PMID:11285665

Corneal Equilibrium Flux as a Function of Corneal Surface Oxygen Tension.

PubMed

Compañ, Vicente; Aguilella-Arzo, Marcel; Weissman, Barry A

2017-06-01

Oxygen is essential for aerobic mammalian cell physiology. Oxygen tension (PO2) should reach a minimum at some position within the corneal stroma, and oxygen flux should be zero, by definition, at this point as well. We found the locations and magnitudes of this "corneal equilibrium flux" (xmin) and explored its physiological implications. We used an application of the Monod kinetic model to calculate xmin for normal human cornea as anterior surface PO2 changes from 155 to 20 mmHg. We find that xmin deepens, broadens, and advances from 1.25 μm above the endothelial-aqueous humor surface toward the epithelium (reaching a position 320 μm above the endothelial-aqueous humor surface) as anterior corneal surface PO2 decreases from 155 to 20 mmHg. Our model supports an anterior corneal oxygen flux of 9 μL O2 · cm · h and an epithelial oxygen consumption of approximately 4 μL O2 · cm · h. Only at the highest anterior corneal PO2 does our model predict that oxygen diffuses all the way through the cornea to perhaps reach the anterior chamber. Of most interest, corneal oxygen consumption should be supported down to a corneal surface PO2 of 60 to 80 mmHg but declines below this range. We conclude that the critical oxygen tension for hypoxia induced corneal swelling is more likely this range rather than a fixed value.

Influence of Pre-Freezing Temperature on the Corneal Endothelial Cytocompatibility and Cell Delivery Performance of Porous Hyaluronic Acid Hydrogel Carriers.

PubMed

Lai, Jui-Yang

2015-08-11

The development of porous hyaluronic acid (HA) hydrogels for corneal endothelial tissue engineering is attractive because they can be used as functional cell delivery carriers to help in the reconstruction of damaged areas. The purpose of this study was to investigate the corneal endothelial cytocompatibility and cell delivery performance of porous HA hydrogel biomaterials fabricated at different pre-freezing temperatures. As compared to their counterparts prepared at -80 °C, the HA samples fabricated at higher pre-freezing temperature (i.e., 0 °C) exhibited a larger pore size and higher porosity, thereby leading to lower resistance to glucose permeation. Live/dead assays and gene expression analyses showed that the restricted porous structure of HA carriers decreases the viability and ionic pump function of cultured corneal endothelial cells (CECs). The results also indicated that the porous hydrogel biomaterials fabricated at high pre-freezing temperature seem to be more compatible with rabbit CECs. In an animal model of corneal endothelial dysfunction, the wounded rabbit corneas receiving bioengineered CEC sheets and restricted porous-structured HA carriers demonstrated poor tissue reconstruction. The therapeutic efficacy of cell sheet transplants can be improved by using carrier materials prepared at high pre-freezing temperature. Our findings suggest that the cryogenic operation temperature-mediated pore microstructure of HA carriers plays an important role in corneal endothelial cytocompatibility and cell delivery performance.

Regulation of Corneal Stroma Extracellular Matrix Assembly

PubMed Central

Chen, Shoujun; Mienaltowski, Michael J.; Birk, David E.

2014-01-01

The transparent cornea is the major refractive element of the eye. A finely controlled assembly of the stromal extracellular matrix is critical to corneal function, as well as in establishing the appropriate mechanical stability required to maintain corneal shape and curvature. In the stroma, homogeneous, small diameter collagen fibrils, regularly packed with a highly ordered hierarchical organization, are essential for function. This review focuses on corneal stroma assembly and the regulation of collagen fibrillogenesis. Corneal collagen fibrillogenesis involves multiple molecules interacting in sequential steps, as well as interactions between keratocytes and stroma matrix components. The stroma has the highest collagen V:I ratio in the body. Collagen V regulates the nucleation of protofibril assembly, thus controlling the number of fibrils and assembly of smaller diameter fibrils in the stroma. The corneal stroma is also enriched in small leucine-rich proteoglycans (SLRPs) that cooperate in a temporal and spatial manner to regulate linear and lateral collagen fibril growth. In addition, the fibril-associated collagens (FACITs) such as collagen XII and collagen XIV have roles in the regulation of fibril packing and inter-lamellar interactions. A communicating keratocyte network contributes to the overall and long-range regulation of stromal extracellular matrix assembly, by creating micro-domains where the sequential steps in stromal matrix assembly are controlled. Keratocytes control the synthesis of extracellular matrix components, which interact with the keratocytes dynamically to coordinate the regulatory steps into a cohesive process. Mutations or deficiencies in stromal regulatory molecules result in altered interactions and deficiencies in both transparency and refraction, leading to corneal stroma pathobiology such as stromal dystrophies, cornea plana and keratoconus. PMID:25819456

Protein-Based Drug-Delivery Materials

PubMed Central

Jao, Dave; Xue, Ye; Medina, Jethro; Hu, Xiao

2017-01-01

There is a pressing need for long-term, controlled drug release for sustained treatment of chronic or persistent medical conditions and diseases. Guided drug delivery is difficult because therapeutic compounds need to survive numerous transport barriers and binding targets throughout the body. Nanoscale protein-based polymers are increasingly used for drug and vaccine delivery to cross these biological barriers and through blood circulation to their molecular site of action. Protein-based polymers compared to synthetic polymers have the advantages of good biocompatibility, biodegradability, environmental sustainability, cost effectiveness and availability. This review addresses the sources of protein-based polymers, compares the similarity and differences, and highlights characteristic properties and functionality of these protein materials for sustained and controlled drug release. Targeted drug delivery using highly functional multicomponent protein composites to guide active drugs to the site of interest will also be discussed. A systematical elucidation of drug-delivery efficiency in the case of molecular weight, particle size, shape, morphology, and porosity of materials will then be demonstrated to achieve increased drug absorption. Finally, several important biomedical applications of protein-based materials with drug-delivery function—including bone healing, antibiotic release, wound healing, and corneal regeneration, as well as diabetes, neuroinflammation and cancer treatments—are summarized at the end of this review. PMID:28772877

Evaluation of possible factors affecting contrast sensitivity function in patients with primary Sjögren's syndrome.

PubMed

Arikan, Sedat; Gokmen, Ferhat; Comez, Arzu Taskiran; Gencer, Baran; Kara, Selcuk; Akbal, Ayla

2015-01-01

The contrast sensitivity (CS) function in patients with primary Sjögren's syndrome (pSS) may be impaired either frequently as a result of dry eye diseases or rarely as a result of optic neuropathy. In this study, we aimed to evaluate the CS function in pSS patients as well as to assess corneal aberrations and thickness of the peripapillary retinal nerve fiber layer (pRNFL). Fourteen eyes of 14 pSS patients (pSS group) and 14 eyes of 14 healthy participants (control group) were subjected to assessment of CS at the spatial frequencies of 1.5, 3.0, 6.0, 12, and 18 cycles/degree (cpd) using a functional visual acuity contrast test (FACT); measurement of corneal high-order aberrations (HOAs) in terms of coma-like, spherical-like, and total HOAs using Scheimpflug corneal topography; and measurement of the thickness of both the macular ganglion cell-inner plexiform layer (mGCIPL) and pRNFL in all quadrants using optical coherence tomography. None of the participants were under treatment with artificial tears. The results of the CS test did not differ between the 2 groups at all spatial frequencies (p>0.05). In addition, there were no statistically significant differences between the 2 groups in terms of corneal HOAs (p>0.05) and thickness of mGCIPL (p>0.05). However, among all quadrants, only the inferior quadrant of pRNFL in pSS patients was statistically significantly thinner than that in the healthy participants (p=0.04). The CS function in pSS patients can be maintained with normal thickness of both pRNFL and mGCIPL and with lack of increased corneal HOAs, which may be present even in the absence of artificial tear usage.

Validation of Catquest-9SF-A Visual Disability Instrument to Evaluate Patient Function After Corneal Transplantation.

PubMed

Claesson, Margareta; Armitage, W John; Byström, Berit; Montan, Per; Samolov, Branka; Stenvi, Ulf; Lundström, Mats

2017-09-01

Catquest-9SF is a 9-item visual disability questionnaire developed for evaluating patient-reported outcome measures after cataract surgery. The aim of this study was to use Rasch analysis to determine the responsiveness of Catquest-9SF for corneal transplant patients. Patients who underwent corneal transplantation primarily to improve vision were included. One group (n = 199) completed the Catquest-9SF questionnaire before corneal transplantation and a second independent group (n = 199) completed the questionnaire 2 years after surgery. All patients were recorded in the Swedish Cornea Registry, which provided clinical and demographic data for the study. Winsteps software v.3.91.0 (Winsteps.com, Beaverton, OR) was used to assess the fit of the Catquest-9SF data to the Rasch model. Rasch analysis showed that Catquest-9SF applied to corneal transplant patients was unidimensional (infit range, 0.73-1.32; outfit range, 0.81-1.35), and therefore, measured a single underlying construct (visual disability). The Rasch model explained 68.5% of raw variance. The response categories of the 9-item questionnaire were ordered, and the category thresholds were well defined. Item difficulty matched the level of patients' ability (0.36 logit difference between the means). Precision in terms of person separation (3.09) and person reliability (0.91) was good. Differential item functioning was notable for only 1 item (satisfaction with vision), which had a differential item functioning contrast of 1.08 logit. Rasch analysis showed that Catquest-9SF is a valid instrument for measuring visual disability in patients who have undergone corneal transplantation primarily to improve vision.

Functional assessment of SLC4A11, an integral membrane protein mutated in corneal dystrophies

PubMed Central

Loganathan, Sampath K.; Schneider, Hans-Peter; Morgan, Patricio E.; Deitmer, Joachim W.

2016-01-01

SLC4A11, a member of the SLC4 family of bicarbonate transporters, is a widely expressed integral membrane protein, abundant in kidney and cornea. Mutations of SLC4A11 cause some cases of the blinding corneal dystrophies, congenital hereditary endothelial dystrophy, and Fuchs endothelial corneal dystrophy. These diseases are marked by fluid accumulation in the corneal stroma, secondary to defective fluid reabsorption by the corneal endothelium. The role of SLC4A11 in these corneal dystrophies is not firmly established, as SLC4A11 function remains unclear. To clarify the normal function(s) of SLC4A11, we characterized the protein following expression in the simple, low-background expression system Xenopus laevis oocytes. Since plant and fungal SLC4A11 orthologs transport borate, we measured cell swelling associated with accumulation of solute borate. The plant water/borate transporter NIP5;1 manifested borate transport, whereas human SLC4A11 did not. SLC4A11 supported osmotically driven water accumulation that was electroneutral and Na+ independent. Studies in oocytes and HEK293 cells could not detect Na+-coupled HCO3− transport or Cl−/HCO3− exchange by SLC4A11. SLC4A11 mediated electroneutral NH3 transport in oocytes. Voltage-dependent OH− or H+ movement was not measurable in SLC4A11-expressing oocytes, but SLC4A11-expressing HEK293 cells manifested low-level cytosolic acidification at baseline. In mammalian cells, but not oocytes, OH−/H+ conductance may arise when SLC4A11 activates another protein or itself is activated by another protein. These data argue against a role of human SLC4A11 in bicarbonate or borate transport. This work provides additional support for water and ammonia transport by SLC4A11. When expressed in oocytes, SLC4A11 transported NH3, not NH3/H+. PMID:27558157

Corneal tissue water content mapping with THz imaging: preliminary clinical results (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sung, Shijun; Bajwa, Neha; Deng, Sophie X.; Taylor, Zachary; Grundfest, Warren

2016-03-01

Well-regulated corneal water content is critical for ocular health and function and can be adversely affected by a number of diseases and injuries. Current clinical practice limits detection of unhealthy corneal water content levels to central corneal thickness measurements performed by ultrasound or optical coherence tomography. Trends revealing increasing or decreasing corneal thickness are fair indicators of corneal water content by individual measurements are highly inaccurate due to the poorly understood relationship between corneal thickness and natural physiologic variation. Recently the utility of THz imaging to accuarately measure corneal water content has been explored on with rabbit models. Preliminary experiments revealed that contact with dielectric windows confounded imaging data and made it nearly impossible to deconvolve thickness variations due to contact from thickness variations due to water content variation. A follow up study with a new optical design allowed the acquisition of rabbit data and the results suggest that the observed, time varying contrast was due entirely to the water dynamics of the cornea. This paper presents the first ever in vivo images of human cornea. Five volunteers with healthy cornea were recruited and their eyes were imaged three times over the course of a few minutes with our novel imaging system. Noticeable changes in corneal reflectivity were observed and attributed to the drying of the tear film. The results suggest that clinically compatible, non-contact corneal imaging is feasible and indicate that signal acquired from non-contact imaging of the cornea is a complicated coupling of stromal water content and tear film.

Effects of Ag+ on ion transport by the corneal epithelium of the rabbit.

PubMed

Klyce, S D; Marshall, W S

1982-01-01

Exposure of the in vitro rabbit corneal epithelium to Ag+ by the addition of AgNO3 (10(-7)-10(-5) M) to the apical surface or by the use of imperfectly chlorided Ag/AgCl half-cells in Ussing-style membrane chambers, greatly increases short-circuit current and transepithelial potential. The early phase (the first 30 min) of the short-circuit current stimulation by Ag+ is linearly dependent on tear-side sodium concentration, is largely a result of a tenfold increase in net Na+ uptake and is incompletely inhibited by ouabain, suggesting that Ag+ increases cation (primarily Na+) conductance of the apical membrane. This mechanism for the Ag+ effect is supported by microelectrode experiments, wherein Ag+ depolarizes specifically the apical barrier potential and increases apical barrier conductance. A later phase in the effect (0.5-3 hr) is characterized by a gradual increase in 36Cl- and 14C-mannitol unidirectional fluxes, by a decline in epithelial resting potential and short-circuit current, by complete ouabain inhibition and by fit to saturation kinetics with respect to Na+ concentration in the bathing media. This phase of the effect apparently reflects a nonselective opening of the paracellular pathway in the epithelium and is rate-limited by Na+ pump activity at the basolateral membrane. Both phases are associated with swelling of the corneal stroma and may be rapidly reversed using thiol agents (reduced glutathione and dithiothreitol). The results suggest that Ag+ may be useful in the study of cation transport by epithelia and the work provides basic physiological information that is pertinent to the prophylactic use of AgNO3 in clinical ophthalmology.

Corneal Staining and Hot Black Tea Compresses.

PubMed

Achiron, Asaf; Birger, Yael; Karmona, Lily; Avizemer, Haggay; Bartov, Elisha; Rahamim, Yocheved; Burgansky-Eliash, Zvia

2017-03-01

Warm compresses are widely touted as an effective treatment for ocular surface disorders. Black tea compresses are a common household remedy, although there is no evidence in the medical literature proving their effect and their use may lead to harmful side effects. To describe a case in which the application of black tea to an eye with a corneal epithelial defect led to anterior stromal discoloration; evaluate the prevalence of hot tea compress use; and analyze, in vitro, the discoloring effect of tea compresses on a model of a porcine eye. We assessed the prevalence of hot tea compresses in our community and explored the effect of warm tea compresses on the cornea when the corneal epithelium's integrity is disrupted. An in vitro experiment in which warm compresses were applied to 18 fresh porcine eyes was performed. In half the eyes a corneal epithelial defect was created and in the other half the epithelium was intact. Both groups were divided into subgroups of three eyes each and treated experimentally with warm black tea compresses, pure water, or chamomile tea compresses. We also performed a study in patients with a history of tea compress use. Brown discoloration of the anterior stroma appeared only in the porcine corneas that had an epithelial defect and were treated with black tea compresses. No other eyes from any group showed discoloration. Of the patients included in our survey, approximately 50% had applied some sort of tea ingredient as a solid compressor or as the hot liquid. An intact corneal epithelium serves as an effective barrier against tea-stain discoloration. Only when this layer is disrupted does the damage occur. Therefore, direct application of black tea (Camellia sinensis) to a cornea with an epithelial defect should be avoided.

Regulation of corneal stroma extracellular matrix assembly.

PubMed

Chen, Shoujun; Mienaltowski, Michael J; Birk, David E

2015-04-01

The transparent cornea is the major refractive element of the eye. A finely controlled assembly of the stromal extracellular matrix is critical to corneal function, as well as in establishing the appropriate mechanical stability required to maintain corneal shape and curvature. In the stroma, homogeneous, small diameter collagen fibrils, regularly packed with a highly ordered hierarchical organization, are essential for function. This review focuses on corneal stroma assembly and the regulation of collagen fibrillogenesis. Corneal collagen fibrillogenesis involves multiple molecules interacting in sequential steps, as well as interactions between keratocytes and stroma matrix components. The stroma has the highest collagen V:I ratio in the body. Collagen V regulates the nucleation of protofibril assembly, thus controlling the number of fibrils and assembly of smaller diameter fibrils in the stroma. The corneal stroma is also enriched in small leucine-rich proteoglycans (SLRPs) that cooperate in a temporal and spatial manner to regulate linear and lateral collagen fibril growth. In addition, the fibril-associated collagens (FACITs) such as collagen XII and collagen XIV have roles in the regulation of fibril packing and inter-lamellar interactions. A communicating keratocyte network contributes to the overall and long-range regulation of stromal extracellular matrix assembly, by creating micro-domains where the sequential steps in stromal matrix assembly are controlled. Keratocytes control the synthesis of extracellular matrix components, which interact with the keratocytes dynamically to coordinate the regulatory steps into a cohesive process. Mutations or deficiencies in stromal regulatory molecules result in altered interactions and deficiencies in both transparency and refraction, leading to corneal stroma pathobiology such as stromal dystrophies, cornea plana and keratoconus. Copyright © 2014 Elsevier Ltd. All rights reserved.

Polysaccharide Hydrogel Combined with Mesenchymal Stem Cells Promotes the Healing of Corneal Alkali Burn in Rats

PubMed Central

Liu, Xun; Yu, Min; Yang, Chunbo; Li, Xiaorong

2015-01-01

Corneal chemical burns are common ophthalmic injuries that may result in permanent visual impairment. Although significant advances have been achieved on the treatment of such cases, the structural and functional restoration of a chemical burn-injured cornea remains challenging. The applications of polysaccharide hydrogel and subconjunctival injection of mesenchymal stem cells (MSCs) have been reported to promote the healing of corneal wounds. In this study, polysaccharide was extracted from Hardy Orchid and mesenchymal stem cells (MSCs) were derived from Sprague-Dawley rats. Supplementation of the polysaccharide significantly enhanced the migration rate of primarily cultured rat corneal epithelial cells. We examined the therapeutic effects of polysaccharide in conjunction with MSCs application on the healing of corneal alkali burns in rats. Compared with either treatment alone, the combination strategy resulted in significantly better recovery of corneal epithelium and reduction in inflammation, neovascularization and opacity of healed cornea. Polysaccharide and MSCs acted additively to increase the expression of anti-inflammatory cytokine (TGF-β), antiangiogenic cytokine (TSP-1) and decrease those promoting inflammation (TNF-α), chemotaxis (MIP-1α and MCP-1) and angiogenesis (VEGF and MMP-2). This study provided evidence that Hardy Orchid derived polysaccharide and MSCs are safe and effective treatments for corneal alkali burns and that their benefits are additive when used in combination. We concluded that combination therapy with polysaccharide and MSCs is a promising clinical treatment for corneal alkali burns and may be applicable for other types of corneal disorder. PMID:25789487

Growing Three-Dimensional Corneal Tissue in a Bioreactor

NASA Technical Reports Server (NTRS)

Spaulding, Glen F.; Goodwin, Thomas J.; Aten, Laurie; Prewett, Tacey; Fitzgerald, Wendy S.; OConnor, Kim; Caldwell, Delmar; Francis, Karen M.

2003-01-01

Spheroids of corneal tissue about 5 mm in diameter have been grown in a bioreactor from an in vitro culture of primary rabbit corneal cells to illustrate the production of optic cells from aggregates and tissue. In comparison with corneal tissues previously grown in vitro by other techniques, this tissue approximates intact corneal tissue more closely in both size and structure. This novel three-dimensional tissue can be used to model cell structures and functions in normal and abnormal corneas. Efforts continue to refine the present in vitro method into one for producing human corneal tissue to overcome the chronic shortage of donors for corneal transplants: The method would be used to prepare corneal tissues, either from in vitro cultures of a patient s own cells or from a well-defined culture from another human donor known to be healthy. As explained in several articles in prior issues of NASA Tech Briefs, generally cylindrical horizontal rotating bioreactors have been developed to provide nutrient-solution environments conducive to the 30 NASA Tech Briefs, October 2003 growth of delicate animal cells, with gentle, low-shear flow conditions that keep the cells in suspension without damaging them. The horizontal rotating bioreactor used in this method, denoted by the acronym "HARV," was described in "High-Aspect-Ratio Rotating Cell-Culture Vessel" (MSC-21662), NASA Tech Briefs, Vol. 16, No. 5 (May, 1992), page 150.

Efficacy and Safety Comparison Between Suberoylanilide Hydroxamic Acid and Mitomycin C in Reducing the Risk of Corneal Haze After PRK Treatment In Vivo.

PubMed

Anumanthan, Govindaraj; Sharma, Ajay; Waggoner, Michael; Hamm, Chuck W; Gupta, Suneel; Hesemann, Nathan P; Mohan, Rajiv R

2017-12-01

This study compared the efficacy and safety of suberoylanilide hydroxamic acid (SAHA) and mitomycin C (MMC) up to 4 months in the prevention of corneal haze induced by photorefractive keratectomy (PRK) in rabbits in vivo. Corneal haze in rabbits was produced with -9.00 diopter PRK. A single application of SAHA (25 μM) or MMC (0.02%) was applied topically immediately after PRK. Effects of the two drugs were analyzed by slit-lamp microscope, specular microscope, TUNEL assay, and immunofluorescence. Single topical adjunct use of SAHA (25 μM) or MMC (0.02%) after PRK attenuated more than 95% corneal haze and myofibroblast formation (P < .001). SAHA did not reduce keratocyte density, cause keratocyte apoptosis, or increase immune cell infiltration compared to MMC (P < .01 or .001). Furthermore, SAHA dosing did not compromise corneal endothelial phenotype, density, or function in rabbit eyes, whereas MMC application did (P < .01 or .001). SAHA and MMC significantly decreased corneal haze after PRK in rabbits in vivo. SAHA exhibited significantly reduced short- and long-term damage to the corneal endothelium compared to MMC in rabbits. SAHA is an effective and potentially safer alternative to MMC for the prevention of corneal haze after PRK. Clinical trials are warranted. [J Refract Surg. 2017;33(12):834-839.]. Copyright 2017, SLACK Incorporated.

Femtosecond laser cutting of human corneas for the subbasal nerve plexus evaluation.

PubMed

Kowtharapu, B S; Marfurt, C; Hovakimyan, M; Will, F; Richter, H; Wree, A; Stachs, O; Guthoff, R F

2017-01-01

Assessment of various morphological parameters of the corneal subbasal nerve plexus is a valuable method of documenting the structural and presumably functional integrity of the corneal innervation in health and disease. The aim of this work is to establish a rapid, reliable and reproducible method for visualization of the human corneal SBP using femtosecond laser cut corneal tissue sections. Trephined healthy corneal buttons were fixed and processed using TissueSurgeon-a femtosecond laser based microtome, to obtain thick tissue sections of the corneal epithelium and anterior stroma cut parallel to the ocular surface within approximately 15 min. A near infrared femtosecond laser was focused on to the cornea approximately 70-90 μm from the anterior surface to induce material separation using TissueSurgeon. The obtained corneal sections were stained following standard immunohistochemical procedures with anti-neuronal β-III tubulin antibody for visualization of the corneal nerves. Sections that contained the epithelium and approximately 20-30 μm of anterior stroma yielded excellent visualisation of the SBP with minimal optical interference from underlying stromal nerves. In conclusion, the results of this study have demonstrated that femtosecond laser cutting of the human cornea offers greater speed, ease and reliability than standard tissue preparation methods for obtaining high quality thick sections of the anterior cornea cut parallel to the ocular surface. © 2016 The Authors Journal of Microscopy © 2016 Royal Microscopical Society.

The clinical and cellular basis of contact lens-related corneal infections

PubMed Central

Robertson, Danielle M; Cavanagh, H Dwight

2008-01-01

Microbial keratitis (MK) is the most visually devastating complication associated with contact lens wear. Pseudomonas aeruginosa (PA) is highly invasive in the corneal epithelium and is responsible for more than half of the reported cases of contact lens-related MK. To protect against Pseudomonas-mediated MK, the corneal epithelium has evolved overlapping defense mechanisms that function to protect the ocular surface from microbial invasion. Research has shown that contact lens wear disrupts these protective mechanisms through breakdown of normal homeostatic surface renewal as well as damaging the corneal surface, exposing underlying cell membrane receptors that bind and internalize PA through the formation of lipid rafts. Human clinical trials have shown that initial adherence of PA with resulting increased risk for microbial infection is mediated in part by contact lens oxygen transmissibility. Recently, chemical preserved multipurpose solutions (MPS) have been implicated in increasing PA adherence to corneal epithelial cells, in addition to inducing significant levels of toxic staining when used in conjunction with specific silicone hydrogel lenses. This review summarizes what is currently known about the relationship between contact lenses, the corneal epithelium, MPS, and infection. PMID:19277209

Importance of accurately assessing biomechanics of the cornea.

PubMed

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.

Electrophysiologic and morphologic effects of ophthalmic preparations on rabbit cornea epithelium.

PubMed

Burstein, N L; Klyce, S D

1977-10-01

The effects of several components of ophthalmic preparations on isolated rabbit cornea were studied by continuous electrophysiologic monitoring followed by fixation for scanning electron microscopy (SEM). Benzalkonium chloride (0.001 percent), thimerosal (0.0004 percent), and amphotericin B (0.0025 percent) all briefly increased ion transport, then greatly decreased epithelial resistance. Severe disruption of surface cell layers occurred simultaneously with resistance decrease. Silver nitrate (0.00017 percent) stimulated transport with less accompanying morphologic damage. Tetracaine (0.05 percent) disrupted epithelial function and caused exfoliation of several cell layers. Chlorobutanol (0.1 percent) produced a nearly complete loss of the squamous cell layer. Chloramphenicol, epinephrine, and pilocarpine produced minor changes in structure and electrophysiology at full clinical concentration. It was concluded that low concentrations of preservatives in ophthalmic preparations disrupt the barrier and transport properties of the corneal epithelium.

Optical transfer function in corneal topography for clinical contrast sensitivity analysis

NASA Astrophysics Data System (ADS)

Bende, Thomas; Jean, Benedikt J.; Oltrup, Theo

2000-06-01

Customized ablation aiming to optimize visual acuity in refractive surgery requires objective data on corneal surface, like the contrast sensitivity. Fast ray tracing, using the high resolution 3-D elevation data in conjunction with Snell's law describe the diffraction of the incident rays and the resulting image on a 'virtual retina.' A retroprojection leads to a 'surface quality map.' For objective contrast sensitivity measurement a sinus (or cos) wave of different frequencies is used for a calculated projection in analogy to the clinical contrast sensitivity charts. The projection on the individual cornea surface is analyzed for the Modular Transfer Function (MTF) and the Phase Shift Function (PSF) as a function of frequencies. PSF, not yet clinically used, is a parameter to determine even minimal corneal tilt. The resulting corneal aberration map (CAM) as described here and applied to a 4.5 D PRK (OZD equals 6.5 mm) reveals that the area of minimal aberration measures only 4.2 mm. The CAM can likewise be used to describe the 'quality' of a laser system's ablation pattern based upon the area of minimal optical aberrations. The CAM only describes surface aberration with high resolution, an advantage over wave front sensing which measures all accumulated optical aberrations including the changing ones of the lens during accommodation and the transient ones due to lens aging and early cataract formation.

Diagnosis and management of neurotrophic keratitis

PubMed Central

Sacchetti, Marta; Lambiase, Alessandro

2014-01-01

Neurotrophic keratitis (NK) is a degenerative disease characterized by corneal sensitivity reduction, spontaneous epithelium breakdown, and impairment of corneal healing. Several causes of NK, including herpetic keratitis, diabetes, and ophthalmic and neurosurgical procedures, share the common mechanism of trigeminal damage. Diagnosis of NK requires accurate investigation of clinical ocular and systemic history, complete eye examination, and assessment of corneal sensitivity. All diagnostic procedures to achieve correct diagnosis and classification of NK, including additional examinations such as in vivo confocal microscopy, are reviewed. NK can be classified according to severity of corneal damage, ie, epithelial alterations (stage 1), persistent epithelial defect (stage 2), and corneal ulcer (stage 3). Management of NK should be based on clinical severity, and aimed at promoting corneal healing and preventing progression of the disease to stromal melting and perforation. Concomitant ocular diseases, such as exposure keratitis, dry eye, and limbal stem cell deficiency, negatively influence the outcome of NK and should be treated. Currently, no specific medical treatment exists, and surgical approaches, such as amniotic membrane transplantation and conjunctival flap, are effective in preserving eye integrity, without ameliorating corneal sensitivity or visual function. This review describes experimental and clinical reports showing several novel and potential therapies for NK, including growth factors and metalloprotease inhibitors, as well as three ongoing Phase II clinical trials. PMID:24672223

Rigid Gas Permeable Contact Lens as a Vision-Sparing Tool in Children After Traumatic Corneal Laceration.

PubMed

Elseht, Rabab Mohamed; Nagy, Khaled Ahmed

2018-05-01

To evaluate the clinical value of rigid gas permeable contact lenses in children after traumatic corneal scarring. This comparative study included 15 children (age range: 5.7 to 14 years; mean ± standard deviation = 9.4 ± 2.9 years) with corneal scars and best corrected visual acuity (BCVA) of worse than 20/20, history of penetrating ocular trauma, and/or cataract extraction. All children were advised to wear spherical rigid gas permeable contact lenses for 6 months with a special regimen. Visual acuity was compared before and after fitting. The total and anterior surface aberrations of all children were measured using a corneal topographer before and after treatment. There was a significant improvement in the BCVA after wearing rigid gas permeable contact lenses compared to spectacle visual acuity (P = .001). There was also significant improvement of the keratometric astigmatism (P = .001) and corneal aberrations such as higher order aberrations (P = .008), lower order aberrations, root mean square, and point spread function (P = .001). The optical performance of rigid gas permeable contact lenses has been demonstrated to be effective in the visual rehabilitation of children with traumatic corneal lacerations. Corneal topography was an objective tool for detecting optical disorders. [J Pediatr Ophthalmol Strabismus. 2018;55(3):178-181.]. Copyright 2018, SLACK Incorporated.

Chronic migraine is associated with reduced corneal nerve fiber density and symptoms of dry eye.

PubMed

Kinard, Krista I; Smith, A Gordon; Singleton, J Robinson; Lessard, Margaret K; Katz, Bradley J; Warner, Judith E A; Crum, Alison V; Mifflin, Mark D; Brennan, Kevin C; Digre, Kathleen B

2015-04-01

We used in vivo corneal confocal microscopy to investigate structural differences in the sub-basal corneal nerve plexus in chronic migraine patients and a normal population. We used a validated questionnaire and tests of lacrimal function to determine the prevalence of dry eye in the same group of chronic migraine patients. Activation of the trigeminal system is involved in migraine. Corneal nociceptive sensation is mediated by trigeminal axons that synapse in the gasserian ganglion and the brainstem, and serve nociceptive, protective, and trophic functions. Noninvasive imaging of the corneal sub-basal nerve plexus is possible with in vivo corneal confocal microscopy. For this case-control study, we recruited chronic migraine patients and compared them with a sex- and age-similar group of control subjects. Patients with peripheral neuropathy, a disease known to be associated with a peripheral neuropathy, or prior corneal or intraocular surgery were excluded. Participants underwent in vivo corneal confocal microscopy using a Heidelberg Retinal Tomography III confocal microscope with a Rostock Cornea Module. Nerve fiber length, nerve branch density, nerve fiber density, and tortuosity coefficient were measured using established methodologies. Migraine participants underwent testing of basal tear production with proparacaine, corneal sensitivity assessment with a cotton-tip applicator, measurement of tear break-up time, and completion of a validated dry eye questionnaire. A total of 19 chronic migraine patients and 30 control participants completed the study. There were no significant differences in age or sex. Nerve fiber density was significantly lower in migraine patients compared with controls (48.4 ± 23.5 vs. 71.0 ± 15.0 fibers/mm2 , P < .001). Nerve fiber length was decreased in the chronic migraine group compared with the control group, but this difference was not statistically significant (21.5 ± 11.8 vs. 26.8 ± 5.9 mm/mm2, P < .084). Nerve branch density was similar in the two groups (114.0 ± 92.4 vs. 118.1 ± 55.9 branches/mm2 , P < .864). Tortuosity coefficient and log tortuosity coefficient also were similar in the chronic migraine and control groups. All migraine subjects had symptoms consistent with a diagnosis of dry eye syndrome. We found that in the sample used in this study, the presence of structural changes in nociceptive corneal axons lends further support to the hypothesis that the trigeminal system plays a critical role in the pathogenesis of migraine. In vivo corneal confocal microscopy holds promise as a biomarker for future migraine research as well as for studies examining alterations of corneal innervation. Dry eye symptoms appear to be extremely prevalent in this population. The interrelationships between migraine, corneal nerve architecture, and dry eye will be the subject of future investigations. © 2015 American Headache Society.

Porcine Skin Visible Lesion Thresholds for Near-Infrared Lasers Including Modeling at Two Pulse Durations and Spot Sizes

DTIC Science & Technology

2006-08-01

injuries, including corneal, lenticular , and retinal lesions as a function of pulse duration. American National Standards Institute (ANSI) laser...little for skin effects. Unlike most other laser wavelengths, 1315-nm irradiation has been shown to cause damage at corneal, lenticular , and retinal

Altered morphology and function of the lacrimal functional unit in protein kinase C{alpha} knockout mice.

PubMed

Chen, Zhuo; Li, Zhijie; Basti, Surendra; Farley, William J; Pflugfelder, Stephen C

2010-11-01

Protein kinase C (PKC) α plays a major role in the parasympathetic neural stimulation of lacrimal gland (LG) secretion. It also has been reported to have antiapoptotic properties and to promote cell survival. Therefore, the hypothesis for the present study was that PKCα knockout ((-/-)) mice have impaired ocular surface-lacrimal gland signaling, rendering them susceptible to desiccating stress and impaired corneal epithelial wound healing. In this study, the lacrimal function unit (LFU) and the stressed wound-healing response were examined in PKCα(-/-) mice. In PKCα(+/+) control mice and PKCα(-/-) mice, tear production, osmolarity, and clearance rate were evaluated before and after experimental desiccating stress. Histology and immunofluorescent staining of PKC and epidermal growth factor were performed in tissues of the LFU. Cornified envelope (CE) precursor protein expression and cell proliferation were evaluated. The time course of healing and degree of neutrophil infiltration was evaluated after corneal epithelial wounding. Compared with the PKCα(+/+) mice, the PKCα(-/-) mice were noted to have significantly increased lacrimal gland weight, with enlarged, carbohydrate-rich, PAS-positive acinar cells; increased corneal epithelia permeability, with reduced CE expression; and larger conjunctival epithelial goblet cells. The PKCα(-/-) mice showed more rapid corneal epithelial healing, with less neutrophil infiltration and fewer proliferating cells than did the PKCα(+/+) mice. The PKCα(-/-) mice showed lower tear production, which appeared to be caused by impaired secretion by the LG and conjunctival goblet cells. Despite their altered tear dynamics, the PKCα(-/-) mice demonstrated more rapid corneal epithelial wound healing, perhaps due to decreased neutrophil infiltration.

Effects of androgen replacement therapy on cornea and tear function in men with idiopathic hypogonadotropic hypogonadism.

PubMed

Gokce, Gokcen; Hurmeric, Volkan; Mumcuoglu, Tarkan; Ozge, Gokhan; Basaran, Yalcin; Unal, Hilmi Umut; Bolu, Erol; Mutlu, Fatih Mehmet

2015-05-01

Idiopathic hypogonadotropic hypogonadism (IHH) is an endocrine disorder defined with the presence of typical clinical signs and symptoms plus laboratory confirmation of serum testosterone (T) levels lower than 300 ng/dl. Androgen replacement therapy (ART) is the first-step treatment of male IHH. To date, no clinical trial, which investigates the changes on corneal structure and tear function, of systemic ART in men have been published. The objective of this study was to investigate the effects of ART on cornea and tear function in patients with IHH. This prospective, interventional study was conducted at the Gulhane Military Medical Academy, Ankara, Turkey, a tertiary referral military hospital. Thirty-four eyes of 17 men with IHH patients were evaluated with Schirmer I test, ultrasound pachymeter, applanation tonometer and confocal microscopy. A Testosterone compound (Sustanon® 250 mg) was administered by intramuscular injection in the course of a 3-week period to induce puberty, and human chorionic gonadotropin (Pregnyl® 5000 IU) was administered twice weekly for 3 months to induce fertility. The patients were re-evaluated at the third month of the treatment. Main Outcome Measures were Schirmer score, central corneal thickness (CCT), intraocular pressure (IOP), endothelial cell density, coefficient of variation and cell shape. Schirmer scores showed similar results after the treatment compared to pre-treatment levels (p = 0.14). There was no statistically significant difference in CCT and IOP compared to baseline data (p = 0.96, p = 0.73, respectively), and no significant differences were found in corneal endothelial cell density, percentage of cell size variability or hexagonality (p = 0.83, p = 0.58, p = 0.64, respectively). This is the first study that investigates the effects of ART on corneal structure and tear function in men. ART seems to have no short-term effects on corneal structure and tear function. Further publications of larger, long-term and controlled studies are needed.

Mechanisms of rubbing-related corneal trauma in keratoconus.

PubMed

McMonnies, Charles W

2009-07-01

Corneal scarring in keratoconus, which is observed prior to contact lens wear and in association with a chronic habit of abnormal rubbing, suggests a keratocyte change to a repair phenotype in response to rubbing trauma. This review examines known and putative mechanisms for rubbing-related corneal trauma and cone formation. Responses to eye rubbing (and possible causal links) may include increased corneal temperature, epithelial thinning, increased concentrations of inflammatory mediators in the precorneal tears, abnormal enzyme activity, large intraocular pressure spikes, high hydrostatic tissue pressure, thixotropically reduced ground substance viscosity, temporary displacement of ground substance from the corneal apex, buckling and flexure of fibrils associated with waves of corneal indentation, biomechanically coupled curvature transfer to the cone apex, slippage between collagen fibrils at the cone apex, and changes to keratocytes due to mechanical trauma and/or high hydrostatic pressure, in addition to scar formation. Cone formation appears to depend on a loss of shear strength and may be a consequence of a reduction in ground substance viscosity and glue function, which could allow the cornea to bend and yield to intraocular pressure. For some forms of keratoconus, a reduction in shear strength and cone-forming deformation may be responses to rubbing trauma. Some of the mechanisms for corneal rubbing trauma may be relevant to post-laser-assisted in situ keratomileusis ectasia or complications following other types of corneal surgery. There appear to be indications for the control of chronic habits of abnormal rubbing.

Effect of Povidone Iodine 5% on the Cornea, Vision, and Subjective Comfort.

PubMed

Ridder, William H; Oquindo, Caren; Dhamdhere, Kavita; Burke, James

2017-07-01

To determine the effects of povidone iodine 5% (Betadine 5%) applied to the eye on visual function, corneal integrity, and subjective complaints. Ten subjects were chosen to participate in this study (average age 40.6 ± 19.6; age range 22-68). LogMAR acuity, contrast sensitivity, corneal fluorescein staining, and subjective complaints were measured before and after 60 μl of Betadine 5% or saline were applied to one eye (eligibility visit, baseline, 5, 30, and 60 minutes and 4 and 24 hours post-application). Contrast sensitivity at 14 cpd was determined with a spatial two-alternative, forced choice procedure (Beethoven software). The National Eye Institute (NEI) grid pattern was used to grade corneal staining with sodium fluorescein. To avoid the detrimental effects of sodium fluorescein administration on functional vision, the corneal staining baseline was measured at the eligibility visit. Subjective complaints were monitored using the Schein dry eye questionnaire. The data were analyzed with an ANOVA. Saline administration did not alter logMAR acuity, contrast sensitivity, corneal fluorescein staining, or subjective complaints at any visit. Betadine administration significantly reduced the logMAR acuity, compared to baseline and the saline data, at the 30- and 60-minute visits (all P values <.05). The contrast sensitivity was significantly reduced compared to the baseline and the saline results at 5, 30, and 60 minutes after Betadine application (all P values <.05). The Betadine significantly increased the Schein questionnaire score, compared both to baseline and the saline data, at the 1- and 4-hour visits (all P values <.05). Total corneal staining and the maximum NEI sector staining were significantly different from baseline and from the saline results at every visit (all P values <.05). Betadine 5% application significantly decreases epithelial integrity of the cornea, decreases functional vision, and increases subjective complaints.

Novel mutations of the carbohydrate sulfotransferase-6 (CHST6) gene causing macular corneal dystrophy in India.

PubMed

Sultana, Afia; Sridhar, Mittanamalli S; Jagannathan, Aparna; Balasubramanian, Dorairajan; Kannabiran, Chitra; Klintworth, Gordon K

2003-12-22

Macular corneal dystrophy (MCD) is an autosomal recessive disorder characterized by progressive central haze, confluent punctate opacities and abnormal deposits in the cornea. It is caused by mutations in the carbohydrate sulfotransferase-6 (CHST6) gene, encoding corneal N-acetyl glucosamine-6-O-sulfotransferase (C-GlcNAc-6-ST). We screened the CHST6 gene for mutations in Indian families with MCD, in order to determine the range of pathogenic mutations. Genomic DNA was isolated from peripheral blood leukocytes of patients with MCD and normal controls. The coding regions of the CHST6 gene were amplified using three pairs of primers and amplified products were directly sequenced. We identified 22 (5 nonsense, 5 frameshift, 2 insertion, and 10 missense) mutations in 36 patients from 31 families with MCD, supporting the conclusion that loss of function of this gene is responsible for this corneal disease. Seventeen of these mutations are novel. These data highlight the allelic heterogeneity of macular corneal dystrophy in Indian patients.

Comparison of Eyemetrics and Orbscan automated method to determine horizontal corneal diameter

PubMed Central

Venkataraman, Arvind; Mardi, Sapna K; Pillai, Sarita

2010-01-01

Purpose: To compare horizontal corneal diameter measurements using the Orbscan Eyemetrics function and Orbscan corneal topographer. Materials and Methods: Seventy-three eyes of 37 patients were included in the study. In all cases, the automated white-to-white (WTW) measurements were obtained using Orbscan by two observers. Using the Eyemetrics function, the WTW was measured manually by the same observers from limbus to limbus using the digital caliper passing through the five point corneal reflections on the Orbscan real image. The data was analyzed using SPSS software for correlation, reliability and inter-rater repeatability. Results: The mean horizontal corneal diameter was 11.74 ± 0.32mm (SD) with the Orbscan and 11.92 ± 0.33mm (SD) with Eyemetrics Software-based measurement. A good positive correlation (Spearman r = 0.720, P = 0.026) was found between these two measurements. The coefficient of inter-rater repeatability was 0.89 for the Orbscan and 0.94 for the Eyemetrics software measurements on the anterior segment images. The Bland and Altman analysis showed large limits of agreement between Orbscan WTW and Eyemetrics WTW measurements. The intra-session repeatability scores for repeat measurements for the Orbscan WTW and Eyemetrics measurements were good. Conclusion: Eyemetrics can be used to measure WTW and the Eyemetrics measured WTW was longer than the WTW measured by Orbscan. PMID:20413925

Characteristic of entire corneal topography and tomography for the detection of sub-clinical keratoconus with Zernike polynomials using Pentacam.

PubMed

Xu, Zhe; Li, Weibo; Jiang, Jun; Zhuang, Xiran; Chen, Wei; Peng, Mei; Wang, Jianhua; Lu, Fan; Shen, Meixiao; Wang, Yuanyuan

2017-11-28

The study aimed to characterize the entire corneal topography and tomography for the detection of sub-clinical keratoconus (KC) with a Zernike application method. Normal subjects (n = 147; 147 eyes), sub-clinical KC patients (n = 77; 77 eyes), and KC patients (n = 139; 139 eyes) were imaged with the Pentacam HR system. The entire corneal data of pachymetry and elevation of both the anterior and posterior surfaces were exported from the Pentacam HR software. Zernike polynomials fitting was used to quantify the 3D distribution of the corneal thickness and surface elevation. The root mean square (RMS) values for each order and the total high-order irregularity were calculated. Multimeric discriminant functions combined with individual indices were built using linear step discriminant analysis. Receiver operating characteristic curves determined the diagnostic accuracy (area under the curve, AUC). The 3rd-order RMS of the posterior surface (AUC: 0.928) obtained the highest discriminating capability in sub-clinical KC eyes. The multimeric function, which consisted of the Zernike fitting indices of corneal posterior elevation, showed the highest discriminant ability (AUC: 0.951). Indices generated from the elevation of posterior surface and thickness measurements over the entire cornea using the Zernike method based on the Pentacam HR system were able to identify very early KC.

Efficient and safe gene delivery to human corneal endothelium using magnetic nanoparticles.

PubMed

Czugala, Marta; Mykhaylyk, Olga; Böhler, Philip; Onderka, Jasmine; Stork, Björn; Wesselborg, Sebastian; Kruse, Friedrich E; Plank, Christian; Singer, Bernhard B; Fuchsluger, Thomas A

2016-07-01

To develop a safe and efficient method for targeted, anti-apoptotic gene therapy of corneal endothelial cells (CECs). Magnetofection (MF), a combination of lipofection with magnetic nanoparticles (MNPs; PEI-Mag2, SO-Mag5, PalD1-Mag1), was tested in human CECs and in explanted human corneas. Effects on cell viability and function were investigated. Immunocompatibility was assessed in human peripheral blood mononuclear cells. Silica iron-oxide MNPs (SO-Mag5) combined with X-tremeGENE-HP achieved high transfection efficiency in human CECs and explanted human corneas, without altering cell viability or function. Magnetofection caused no immunomodulatory effects in human peripheral blood mononuclear cells. Magnetofection with anti-apoptotic P35 gene effectively blocked apoptosis in CECs. Magnetofection is a promising tool for gene therapy of corneal endothelial cells with potential for targeted on-site delivery.

A Novel Tectonic Keratoplasty with Femtosecond Laser Intrastromal Lenticule for Corneal Ulcer and Perforation

PubMed Central

Jiang, Yang; Li, Ying; Liu, Xiao-Wei; Xu, Jing

2016-01-01

Background: Small incision refractive lenticule extraction (SMILE) is an effective laser procedure that treats myopia. This research was to describe a novel approach to treat corneal ulcer or perforation using the corneal lenticules obtained from SMILE and to evaluate the safety and effectiveness of tectonic keratoplasty with femtosecond laser intrastromal lenticule (TEKIL). Methods: A total of twenty patients (22 eyes) were monitored for at least 6 months and were assessed using slit lamp microscopy, optical coherence tomography, and best-corrected visual acuity (BCVA). Postoperative complications throughout the study period were recorded. Results: Corneal ulcer in 14 patients (16 eyes) and corneal perforation in six patients (6 eyes) were treated with TEKIL. The patients were ten females and ten males, with a mean age of 58.5 ± 16.3 years (range: 16–81 years). In this study, the most causes of corneal ulcer or perforation were immunologic causes (54.5%). After TEKIL procedure, global integrity was achieved in all cases. No immune rejection or perforation was detected. The mean BCVA improved from 0.17 ± 0.20 preoperatively to 0.27 ± 0.25 postoperatively at the final follow-up (t = 2.095, P = 0.052). The postoperative BCVA improved in 12 eyes (54.5%) and maintained in nine eyes (40.9%). Vision function successfully maintained in all eyes (100%). In three cases, corneal ulcers were treated by reoperation of TEKIL at 3 months after the initial surgery for the reason that the residual corneal thickness was <250 μm. Conclusions: TEKIL seems to be an effective treatment for corneal ulcer and perforation in the condition of emergency and donor shortage. PMID:27453231

Improvement of chronic corneal opacity in ocular surface disease with prosthetic replacement of the ocular surface ecosystem (PROSE) treatment.

PubMed

Cressey, Anna; Jacobs, Deborah S; Remington, Crystal; Carrasquillo, Karen G

2018-06-01

To demonstrate clearing of chronic corneal opacities and improvement of visual acuity with the use of BostonSight prosthetic replacement of the ocular surface ecosystem (PROSE) treatment in ocular surface disease. We undertook retrospective analysis of the medical records of a series of patients who underwent PROSE treatment from August 2006 to December 2014. Patients were referred for ocular surface disease of various etiologies. Primary inclusion criterion was corneal opacity that improved with PROSE treatment. Patients were excluded if topical steroids or adjuvant therapy used once PROSE treatment was initiated. Underlying disease, prior treatment, clinical presentation, and clinical course were extracted from the medical record. Four patients are included in this series. There were three females and one male; median age at time of treatment initiation was 30 years (range = 0.5-58 years). Median duration of PROSE treatment at time of retrospective analysis was 3.5 years (range = 1-8 years). Two cases had corneal opacification in the context of neurotrophic keratopathy: a unilateral case due to presumed herpes simplex keratitis and a bilateral case due to congenital corneal anesthesia associated with familial dysautonomia. One case had corneal opacity from exposure related to seventh nerve palsy, and one had corneal opacification associated with recurrent surface breakdown, neurotrophic keratopathy, and limbal stem deficiency of uncertain etiology. After consistent wear of prosthetic devices used in PROSE treatment for support of the ocular surface, visual acuity improved and clearing of the opacities was observed, without use of topical steroids or adjuvant therapy. These cases demonstrate clearing of chronic corneal opacity with PROSE treatment for ocular surface disease. This clearing can occur with no adjuvant therapy, suggesting that restoration of ocular surface function and integrity allows for corneal remodeling.

A novel mouse model for neurotrophic keratopathy: trigeminal nerve stereotactic electrolysis through the brain.

PubMed

Ferrari, Giulio; Chauhan, Sunil K; Ueno, Hiroki; Nallasamy, Nambi; Gandolfi, Stefano; Borges, Lawrence; Dana, Reza

2011-04-01

To develop a mouse model of neurotrophic keratopathy by approaching the trigeminal nerve through the brain and to evaluate changes in corneal cell apoptosis and proliferation. Six- to 8-week-old male C57BL/6 mice underwent trigeminal stereotactic electrolysis (TSE) to destroy the ophthalmic branch of the trigeminal nerve. Clinical follow-up using biomicroscopy of the cornea was performed at days 2, 4, 5, and 7. To confirm the effectiveness of the procedure, we examined the gross nerve pathology, blink reflex, and immunohistochemistry of the corneal nerves. TUNEL-positive apoptotic and Ki-67-positive proliferating corneal cells were evaluated to detect changes from the contralateral normal eye. TSE was confirmed by gross histology of the trigeminal nerve and was considered effective if the corneal blink reflex was completely abolished. TSE totally abolished the blink reflex in 70% of mice and significantly reduced it in the remaining 30%. Animals with absent blink reflex were used for subsequent experiments. In these mice, a progressive corneal degeneration developed, with thinning of the corneal epithelium and eventually perforation after 7 days. In all mice, 48 hours after TSE, corneal nerves were not recognizable histologically. Seven days after TSE, an increase in cellular apoptosis in all the corneal layers and a reduction in proliferation in basal epithelial cells were detected consistently in all mice. TSE was able, in most cases, to induce a disease state that reflected clinical neurotrophic keratitis without damaging the periocular structures. Moreover, corneal denervation led to increased apoptosis and reduced proliferation of epithelial cells, formally implicating intact nerve function in regulating epithelial survival and turnover.

A Novel Mouse Model for Neurotrophic Keratopathy: Trigeminal Nerve Stereotactic Electrolysis through the Brain

PubMed Central

Ferrari, Giulio; Chauhan, Sunil K.; Ueno, Hiroki; Nallasamy, Nambi; Gandolfi, Stefano; Borges, Lawrence

2011-01-01

Purpose. To develop a mouse model of neurotrophic keratopathy by approaching the trigeminal nerve through the brain and to evaluate changes in corneal cell apoptosis and proliferation. Methods. Six- to 8-week-old male C57BL/6 mice underwent trigeminal stereotactic electrolysis (TSE) to destroy the ophthalmic branch of the trigeminal nerve. Clinical follow-up using biomicroscopy of the cornea was performed at days 2, 4, 5, and 7. To confirm the effectiveness of the procedure, we examined the gross nerve pathology, blink reflex, and immunohistochemistry of the corneal nerves. TUNEL-positive apoptotic and Ki-67–positive proliferating corneal cells were evaluated to detect changes from the contralateral normal eye. Results. TSE was confirmed by gross histology of the trigeminal nerve and was considered effective if the corneal blink reflex was completely abolished. TSE totally abolished the blink reflex in 70% of mice and significantly reduced it in the remaining 30%. Animals with absent blink reflex were used for subsequent experiments. In these mice, a progressive corneal degeneration developed, with thinning of the corneal epithelium and eventually perforation after 7 days. In all mice, 48 hours after TSE, corneal nerves were not recognizable histologically. Seven days after TSE, an increase in cellular apoptosis in all the corneal layers and a reduction in proliferation in basal epithelial cells were detected consistently in all mice. Conclusions. TSE was able, in most cases, to induce a disease state that reflected clinical neurotrophic keratitis without damaging the periocular structures. Moreover, corneal denervation led to increased apoptosis and reduced proliferation of epithelial cells, formally implicating intact nerve function in regulating epithelial survival and turnover. PMID:21071731

Structural, Morphological, and Functional Correlates of Corneal Endothelial Toxicity Following Corneal Exposure to Sulfur Mustard Vapor

DTIC Science & Technology

2013-10-01

fentanyl patch (25 lg/h) was placed anterior to the scapula. On the day of exposure, rabbits were anesthetized with an intramuscular administration of 15 mg...sterile saline to flush residual agent. Rabbits were returned to cages and provided food and water ad libitum. Fentanyl patches were replaced after 72

Neurturin-deficient mice develop dry eye and keratoconjunctivitis sicca.

PubMed

Song, Xiu Jun; Li, De-Quan; Farley, William; Luo, Li Hui; Heuckeroth, Robert O; Milbrandt, Jeffrey; Pflugfelder, Stephen C

2003-10-01

Neurturin has been identified as a neurotrophic factor for parasympathetic neurons. Neurturin-deficient (NRTN(-/-)) mice have defective parasympathetic innervation of their lacrimal glands. This study was conducted to evaluate tear function and ocular surface phenotype in NRTN(-/-) mice. Determined by tail genomic DNA PCR, 25 NRTN(-/-) mice and 17 neurturin-normal (NRTN(+/+)) mice aged 6 weeks to 4 months were evaluated. Aqueous tear production, tear fluorescein clearance and corneal sensation were serially measured. Corneal permeability to AlexaFluor dextran (AFD; Molecular Probes, Eugene, OR) was measured by a fluorometric assay at 485 nm excitation and 530 nm emission. Histology was evaluated in PAS-stained sections. Mucin and HLA class II (IA) antigen were assessed by immunofluorescent staining. Tear IL-1beta was measured by ELISA, and tear matrix metalloproteinase (MMP)-9 by zymography. Gene expression in the corneal epithelia was analyzed by semiquantitative RT-PCR. In comparison to that in age-matched NRTN(+/+) mice, aqueous tear production, tear fluorescein clearance, and corneal sensation were significantly reduced in NRTN(-/-) mice, whereas corneal permeability to AFD was significantly increased. Immunoreactive MUC-4 and -5AC mucin and goblet cell density (P < 0.001) in the conjunctiva of NRTN(-/-) mice were lower than in NRTN(+/+) mice. The expression of MUC-1 and -4 mRNA by the corneal epithelium was reduced in NRTN(-/-) mice. There were a significantly greater number of IA antigen-positive conjunctival epithelial cells in NRTN(-/-) mice than NRTN(+/+) mice. Tear fluid IL-1beta and MMP-9 concentrations and the expression of IL-1beta, TNF-alpha, macrophage inflammatory protein (MIP)-2, cytokine-induced neutrophil chemoattractant (KC), and MMP-9 mRNA by the corneal epithelia were significantly increased in NRTN(-/-) mice, compared with NRTN(+/+) mice. Neurturin-deficient mice show phenotypic changes and ocular surface inflammation that mimic human keratoconjunctivitis sicca. This model supports the importance of a functional ocular surface-central nervous system-lacrimal gland sensory-autonomic neural network in maintaining ocular surface health and homeostasis.

Effects of eye drops containing a mixture of omega-3 essential fatty acids and hyaluronic acid on the ocular surface in desiccating stress-induced murine dry eye.

PubMed

Li, Zhengri; Choi, Jung-Han; Oh, Han-Jin; Park, Soo-Hyun; Lee, Jee-Bum; Yoon, Kyung Chul

2014-09-01

To investigate the efficacy of the topical application of omega-3 essential fatty acids (EFAs) and hyaluronic acid (HA) mixtures in a mouse model of experimental dry eye (EDE). Eye drops consisting of 0.1% HA, 0.02%, or 0.2% omega-3 EFAs alone and mixture of 0.02%, or 0.2% omega-3 EFAs and 0.1% HA were applied in desiccating stress-induced murine dry eye. Corneal irregularity scores and fluorescein staining scores were measured 5 and 10 days after treatment. Levels of interleukin (IL)-1β, -17, and interferon gamma-induced protein (IP)-10 were measured in the conjunctiva at 10 days using a multiplex immunobead assay. The concentrations of hexanoyl-lys (HEL) and 4-hydroxynonenal (4-HNE) in conjunctiva tissue were measured with enzyme-linked immunosorbent assays. Mice treated with the mixture containing 0.2% omega-3 EFAs showed a significant improvement in corneal irregularity scores and corneal fluorescein staining scores compared with EDE, HA, 0.02% or 0.2% omega-3 EFAs alone, and 0.02% omega-3 EFAs mixture-treated mice. A significant decrease in the levels of IL-1β, -17, and IP-10 were observed in the 0.2% EFAs mixture-treated group, compared with the other groups. In the mice treated with the mixture containing 0.2% omega-3 EFAs, the concentration of 4-HNE was also lower than the other groups. Although 0.2% omega-3 EFAs alone group also had a significant improvement in corneal irregularity scores and IL-17, IL-10, and 4 HNE levels compared with the other groups, the efficacy was lower than 0.2% omega-3 mixture group. Topically applied eye drops containing a mixture of omega-3 EFAs and HA could improve corneal irregularity and corneal epithelial barrier disruption, and decrease inflammatory cytokines and oxidative stress markers on the ocular surface. Topical omega-3 EFAs and HA mixture may have a greater therapeutic effect on clinical signs and inflammation of dry eye compared with HA artificial tears.

Ribonuclease 5 facilitates corneal endothelial wound healing via activation of PI3-kinase/Akt pathway

PubMed Central

Kim, Kyoung Woo; Park, Soo Hyun; Lee, Soo Jin; Kim, Jae Chan

2016-01-01

To maintain corneal transparency, corneal endothelial cells (CECs) exert a pump function against aqueous inflow. However, human CECs are arrested in the G1-phase and non-proliferative in vivo. Thus, treatment of corneal endothelial decompensation is limited to corneal transplantation, and grafts are vulnerable to immune rejection. Here, we show that ribonuclease (RNase) 5 is more highly expressed in normal human CECs compared to decompensated tissues. Furthermore, RNase 5 up-regulated survival of CECs and accelerated corneal endothelial wound healing in an in vitro wound of human CECs and an in vivo cryo-damaged rabbit model. RNase 5 treatment rapidly induced accumulation of cytoplasmic RNase 5 into the nucleus, and activated PI3-kinase/Akt pathway in human CECs. Moreover, inhibition of nuclear translocation of RNase 5 using neomycin reversed RNase 5-induced Akt activation. As a potential strategy for proliferation enhancement, RNase 5 increased the population of 5-bromo-2′-deoxyuridine (BrdU)-incorporated proliferating CECs with concomitant PI3-kinase/Akt activation, especially in CECs deprived of contact-inhibition. Specifically, RNase 5 suppressed p27 and up-regulated cyclin D1, D3, and E by activating PI3-kinase/Akt in CECs to initiate cell cycle progression. Together, our data indicate that RNase 5 facilitates corneal endothelial wound healing, and identify RNase 5 as a novel target for therapeutic exploitation. PMID:27526633

Surface Topography and Mechanical Strain Promote Keratocyte Phenotype and Extracellular Matrix Formation in a Biomimetic 3D Corneal Model.

PubMed

Zhang, Wei; Chen, Jialin; Backman, Ludvig J; Malm, Adam D; Danielson, Patrik

2017-03-01

The optimal functionality of the native corneal stroma is mainly dependent on the well-ordered arrangement of extracellular matrix (ECM) and the pressurized structure. In order to develop an in vitro corneal model, it is crucial to mimic the in vivo microenvironment of the cornea. In this study, the influence of surface topography and mechanical strain on keratocyte phenotype and ECM formation within a biomimetic 3D corneal model is studied. By modifying the surface topography of materials, it is found that patterned silk fibroin film with 600 grooves mm -1 optimally supports cell alignment and ECM arrangement. Furthermore, treatment with 3% dome-shaped mechanical strain, which resembles the shape and mechanics of native cornea, significantly enhances the expression of keratocyte markers as compared to flat-shaped strain. Accordingly, a biomimetic 3D corneal model, in the form of a collagen-modified, silk fibroin-patterned construct subjected to 3% dome-shaped strain, is created. Compared to traditional 2D cultures, it supports a significantly higher expression of keratocyte and ECM markers, and in conclusion better maintains keratocyte phenotype, alignment, and fusiform cell shape. Therefore, the novel biomimetic 3D corneal model developed in this study serves as a useful in vitro 3D culture model to improve current 2D cultures for corneal studies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structural and functional changes in corneal innervation after laser in situ keratomileusis and their relationship with dry eye.

PubMed

Chao, Cecilia; Stapleton, Fiona; Zhou, Xiangtian; Chen, Shihao; Zhou, Shi; Golebiowski, Blanka

2015-11-01

The most likely etiology of post-LASIK dry eye is corneal nerve damage; however, no direct relationship between post-LASIK dry eye symptoms and nerve damage has been established, and limited information is available about the relationship between dry eye signs and corneal reinnervation after LASIK. Tear neuropeptides (SP and CGRP) are important in the maintenance of corneal nerve health, but the impact of LASIK has not yet been studied. This study evaluated changes in nerve morphology, tear neuropeptide, and dry eye, so as to establish the relationship between reinnervation and dry eye and to assess the role of tear neuropeptides in reinnervation post-LASIK. Twenty non-dry eye volunteers who had undergone bilateral myopic-LASIK completed this study. Corneal nerve morphology (density, width, interconnections, and tortuosity), SP and CGRP concentration, and dry eye were monitored over time prior to, 1 day, 1 week, 1, 3, and 6 months post-LASIK. Dry eye symptoms and tear function, except for osmolarity (P = 0.003), remained unchanged post-LASIK. Corneal nerve morphology decreased immediately, and did not return to preoperative levels by 6 months post-LASIK (P < 0.001). Increased tear SP concentration was observed 3 months post-LASIK (P < 0.001). Associations between reinnervation as measured by increased density and lower tear SP (P = 0.03), and between increased density and decreased dry eye symptoms (P = 0.01) were found post-LASIK. An inverse relationship between reinnervation post-LASIK and dry eye symptoms was found, confirming that post-LASIK dry eye is a neuropathic disease. This study is the first to demonstrate an association between tear SP and post-LASIK reinnervation, suggesting that strategies for manipulating neuropeptide concentration to improve reinnervation may improve ocular comfort post-LASIK.

Analysis of the Viscoelastic Properties of the Human Cornea Using Scheimpflug Imaging in Inflation Experiment of Eye Globes

PubMed Central

Lombardo, Giuseppe; Serrao, Sebastiano; Rosati, Marianna; Lombardo, Marco

2014-01-01

Purpose To demonstrate a Scheimpflug-based imaging procedure for investigating the depth- and time-dependent strain response of the human cornea to inflation testing of whole eye globes. Methods Six specimens, three of which with intact corneal epithelium, were mounted in a customized apparatus within a humidity and temperature-monitored wet chamber. Each specimen was subjected to two mechanical tests in order to measure corneal strain resulting from application of cyclic (cyclic regimen) and constant (creep regimen) stress by changing the intra-ocular pressure (IOP) within physiological ranges (18–42 mmHg). Corneal shape changes were analyzed as a function of IOP and both corneal stress-strain curves and creep curves were generated. Results The procedure was highly accurate and repeatable. Upon cyclic stress application, a biomechanical corneal elasticity gradient was found in the front-back direction. The average Young's modulus of the anterior cornea ranged between 2.28±0.87 MPa and 3.30±0.90 MPa in specimens with and without intact epithelium (P = 0.05) respectively. The Young's modulus of the posterior cornea was on average 0.21±0.09 MPa and 0.17±0.06 MPa (P>0.05) respectively. The time-dependent strain response of the cornea to creep testing was quantified by fitting data to a modified Zener model for extracting both the relaxation time and compliance function. Conclusion Cyclic and creep mechanical tests are valuable for investigating the strain response of the intact human cornea within physiological IOP ranges, providing meaningful results that can be translated to clinic. The presence of epithelium influences the results of anterior corneal shape changes when monitoring deformation via Scheimpflug imaging in inflation experiments of whole eye globes. PMID:25397674

Evaluating alternative stem cell hypotheses for adult corneal epithelial maintenance

PubMed Central

West, John D; Dorà, Natalie J; Collinson, J Martin

2015-01-01

In this review we evaluate evidence for three different hypotheses that explain how the corneal epithelium is maintained. The limbal epithelial stem cell (LESC) hypothesis is most widely accepted. This proposes that stem cells in the basal layer of the limbal epithelium, at the periphery of the cornea, maintain themselves and also produce transient (or transit) amplifying cells (TACs). TACs then move centripetally to the centre of the cornea in the basal layer of the corneal epithelium and also replenish cells in the overlying suprabasal layers. The LESCs maintain the corneal epithelium during normal homeostasis and become more active to repair significant wounds. Second, the corneal epithelial stem cell (CESC) hypothesis postulates that, during normal homeostasis, stem cells distributed throughout the basal corneal epithelium, maintain the tissue. According to this hypothesis, LESCs are present in the limbus but are only active during wound healing. We also consider a third possibility, that the corneal epithelium is maintained during normal homeostasis by proliferation of basal corneal epithelial cells without any input from stem cells. After reviewing the published evidence, we conclude that the LESC and CESC hypotheses are consistent with more of the evidence than the third hypothesis, so we do not consider this further. The LESC and CESC hypotheses each have difficulty accounting for one main type of evidence so we evaluate the two key lines of evidence that discriminate between them. Finally, we discuss how lineage-tracing experiments have begun to resolve the debate in favour of the LESC hypothesis. Nevertheless, it also seems likely that some basal corneal epithelial cells can act as long-term progenitors if limbal stem cell function is compromised. Thus, this aspect of the CESC hypothesis may have a lasting impact on our understanding of corneal epithelial maintenance, even if it is eventually shown that stem cells are restricted to the limbus as proposed by the LESC hypothesis. PMID:25815115

Altered Morphology and Function of the Lacrimal Functional Unit in Protein Kinase Cα Knockout Mice

PubMed Central

Chen, Zhuo; Li, Zhijie; Basti, Surendra; Farley, William J.

2010-01-01

Purpose. Protein kinase C (PKC) α plays a major role in the parasympathetic neural stimulation of lacrimal gland (LG) secretion. It also has been reported to have antiapoptotic properties and to promote cell survival. Therefore, the hypothesis for the present study was that PKCα knockout (−/−) mice have impaired ocular surface–lacrimal gland signaling, rendering them susceptible to desiccating stress and impaired corneal epithelial wound healing. In this study, the lacrimal function unit (LFU) and the stressed wound-healing response were examined in PKCα−/− mice. Methods. In PKCα+/+ control mice and PKCα−/− mice, tear production, osmolarity, and clearance rate were evaluated before and after experimental desiccating stress. Histology and immunofluorescent staining of PKC and epidermal growth factor were performed in tissues of the LFU. Cornified envelope (CE) precursor protein expression and cell proliferation were evaluated. The time course of healing and degree of neutrophil infiltration was evaluated after corneal epithelial wounding. Results. Compared with the PKCα+/+ mice, the PKCα−/− mice were noted to have significantly increased lacrimal gland weight, with enlarged, carbohydrate-rich, PAS-positive acinar cells; increased corneal epithelia permeability, with reduced CE expression; and larger conjunctival epithelial goblet cells. The PKCα−/− mice showed more rapid corneal epithelial healing, with less neutrophil infiltration and fewer proliferating cells than did the PKCα+/+ mice. Conclusions. The PKCα−/− mice showed lower tear production, which appeared to be caused by impaired secretion by the LG and conjunctival goblet cells. Despite their altered tear dynamics, the PKCα−/− mice demonstrated more rapid corneal epithelial wound healing, perhaps due to decreased neutrophil infiltration. PMID:20505191

Trends and Determinants of Familial Consent for Corneal Donation in Chinese.

PubMed

Lee, Allie; Ni, Michael Y; Luk, Amanda C K; Lau, Jessie K P; Lam, Karen S Y; Li, Tom K; Wong, Catherine S M; Wong, Victoria W Y

2017-03-01

Corneal transplantation is the treatment of choice for many corneal diseases. At present, there is a global shortage of corneal transplant tissues, and failure to obtain consent from families of potential donors is a major limiting factor in tissue procurement. All family members of potential donors after cardiac death approached by the local eye bank staff members from January 2008 to December 2014 in Hong Kong were included. Reasons for consent or refusal and sociodemographic details of the deceased and the family members approached were reviewed. Trends in consent rates from 2008 to 2014 were examined. Multivariable logistic regression was performed to examine determinants of donation among cases from 2013 to 2014. A total of 1740 cases were identified. The overall consent rate was 36.8%, and the consent rate did not change significantly over the 7-year study period (P = 0.24). The most common reason for consent by family members was "the wish to help others" (86.0%), and the most common reason for refusal was "traditional Chinese culture to keep the body intact after death" (42.7%). From the multivariable analysis in the subset of cases from 2013 to 2014 (n = 628), family members were more likely to consent when the deceased was female (adjusted odds ratio 1.45, P = 0.03), with a do-not-resuscitate order (adjusted odds ratio 2.27, P < 0.001). The consent rate for eye donation did not change significantly from 2008 to 2014. Our findings suggest that health education and promotion campaigns need to address cultural barriers to organ donation.

Creation of nano eye-drops and effective drug delivery to the interior of the eye

NASA Astrophysics Data System (ADS)

Ikuta, Yoshikazu; Aoyagi, Shigenobu; Tanaka, Yuji; Sato, Kota; Inada, Satoshi; Koseki, Yoshitaka; Onodera, Tsunenobu; Oikawa, Hidetoshi; Kasai, Hitoshi

2017-03-01

Nano eye-drops are a new type of ophthalmic treatment with increased potency and reduced side effects. Compounds in conventional eye-drops barely penetrate into the eye because the cornea, located at the surface of eye, has a strong barrier function for preventing invasion of hydrophilic or large-sized materials from the outside. In this work, we describe the utility of nano eye-drops utilising brinzolamide, a commercially available glaucoma treatment drug, as a target compound. Fabrication of the nanoparticles of brinzolamide prodrug increases the eye penetration rate and results in high drug efficacy, compared with that of commercially available brinzolamide eye-drops formulated as micro-sized structures. In addition, the resulting nano eye-drops were not toxic to the corneal epithelium after repeated administration for 1 week. The nano eye-drops may have applications as a next-generation ophthalmic treatment.

Adaptive cornea modeling from keratometric data.

PubMed

Martínez-Finkelshtein, Andrei; López, Darío Ramos; Castro, Gracia M; Alió, Jorge L

2011-07-01

To introduce an iterative, multiscale procedure that allows for better reconstruction of the shape of the anterior surface of the cornea from altimetric data collected by a corneal topographer. The report describes, first, an adaptive, multiscale mathematical algorithm for the parsimonious fit of the corneal surface data that adapts the number of functions used in the reconstruction to the conditions of each cornea. The method also implements a dynamic selection of the parameters and the management of noise. Then, several numerical experiments are performed, comparing it with the results obtained by the standard Zernike-based procedure. The numerical experiments showed that the algorithm exhibits steady exponential error decay, independent of the level of aberration of the cornea. The complexity of each anisotropic Gaussian-basis function in the functional representation is the same, but the parameters vary to fit the current scale. This scale is determined only by the residual errors and not by the number of the iteration. Finally, the position and clustering of the centers, as well as the size of the shape parameters, provides additional spatial information about the regions of higher irregularity. The methodology can be used for the real-time reconstruction of both altimetric data and corneal power maps from the data collected by keratoscopes, such as the Placido ring-based topographers, that will be decisive in early detection of corneal diseases such as keratoconus.

Corneal Crosslinking With Rose Bengal and Green Light: Efficacy and Safety Evaluation.

PubMed

Zhu, Hong; Alt, Clemens; Webb, Robert H; Melki, Samir; Kochevar, Irene E

2016-09-01

To evaluate crosslinking of cornea in vivo using green light activation of Rose Bengal (RGX) and assess potential damaging effects of the green light on retina and iris. Corneas of Dutch belted rabbits were de-epithelialized, then stained with Rose Bengal and exposed to green light, or not further treated. Corneal stiffness was measured by uniaxial tensiometry. Re-epithelialization was assessed by fluorescein fluorescence. Keratocytes were counted on hematoxylin and eosin (H&E)-stained sections, and iris cell damage was assessed by lactate dehydrogenase staining. Thermal effects on the blood-retinal barrier (BRB) were assessed by fluorescein angiography and those on photoreceptors, retinal pigment epithelium (RPE), and choriocapillaris by light microscopy and transmission electron microscopy. RGX (10-min irradiation; 150 J/cm) increased corneal stiffness 1.9-fold on day 1 (1.25 ± 0.21 vs. 2.38 ± 0.59 N/mm; P = 0.036) and 2.8-fold compared with controls on day 28 (1.70 ± 0.74 vs. 4.95 ± 1.86 N/mm; P = 0.003). Keratocytes decreased only in the anterior stroma on day 1 (24.0 ± 3.0 vs. 3.67 ± 4.73, P = 0.003) and recovered by day 28 (37.7 ± 8.9 vs. 34.5 ± 2.4, P = 0.51). Iris cells were not thermally damaged. No evidence of BRB breakdown was detected on days 1 or 28. Retina from RGX-treated eyes seemed normal with RPE cells showing intact nuclei shielded apically by melanosomes, morphologically intact photoreceptor outer segments, normal outer nuclear layer thickness, and choriocapillaris containing intact erythrocytes. The substantial corneal stiffening produced by RGX together with the lack of significant effects on keratocytes and no evidence for retina or iris damage suggest that RGX-initiated corneal crosslinking may be a safe, rapid, and effective treatment.

Free radical development in phacoemulsification cataract surgery.

PubMed

Takahashi, Hiroshi

2005-02-01

Phacoemulsification and aspiration (PEA) has become the most popular cataract surgery, due to the establishment of safe surgical techniques and development of associated instruments. However, corneal endothelial damage still represents a serious complication, as excessive damage can lead to irreversible bullous keratopathy. In addition to causes such as mechanical or heat injuries, free radical formation due to ultrasound has been posited as another cause of corneal endothelium damage in PEA. Ultrasound in aqueous solution induces cavitation, directly causing water molecule disintegration and resulting in the formation of hydroxylradicals, the most potent of the reactive oxygen species. Considering the oxidative insult to endothelial cells caused by free radicals, their presence in the anterior chamber may represent one of the most harmful factors during these procedures. Indeed, some researchers have recently started to evaluate PEA from the perspective of oxidative stress. Conversely, the major ingredient in ophthalmic viscosurgical devices (OVDs), which are indispensable for maintaining the anterior chamber in PEA surgery, is sodium hyaluronate, a known free radical scavenger. OVDs can thus be expected to provide some anti-free radical effect during PEA procedures. In addition, since commercially available OVDs display different properties regarding retention in the anterior chamber during PEA, the anti-free radical effect of OVDs is likely to depend on behavior during irrigation and aspiration. The present study followed standard PEA procedures in an eye model and measured hydroxylradicals in the anterior chamber using electron spin resonance. The kinetics of free radical intensity and effects of several OVDs during clinical PEA were also demonstrated. These studies may be of significance in re-evaluating OVDs as a chemical protectant for corneal endothelium, since the OVD has thus far only been regarded as a physical barrier. In addition, many reports about corneal endothelium damage during PEA have been published, but objective evaluation of various damaging factors has been difficult. The present assay of free radicals in a simulation of clinical PEA offers the first method to quantitatively assess stress on the corneal endothelium.

Corneal changes induced by laser ablation: study of the visual-quality evolution by a customized eye model

NASA Astrophysics Data System (ADS)

Ortiz, D.; Anera, R. G.; Saiz, J. M.; Jiménez, J. R.; Moreno, F.; Jiménez Del Barco, L.; González, F.

2006-11-01

This study focuses on the changes induced in both the asphericity and homogeneity of the cornea for a group of myopic eyes undergoing LASIK surgery. Eyes were characterized by a Kooijman-based customized eye model in which changes were introduced in the form of Gaussian-distributed refractive-index variations of given correlation length for the inhomogeneities and in the form of an expression, based on the modified Munnerlyn's paraxial formula, for the post-LASIK asphericity. Visual quality was evaluated in terms of the Modulation Transfer Function and the Point-Spread Function. The results show that, on average, the evolution of visual acuity is consistent with the change in corneal asphericity, while the evolution of contrast sensitivity requires a loss in corneal homogeneity in order to be explained. By including both effects in the model, the overall model performance in predicting visual quality is improved.

Distribution of curvature of 3D nonrotational surfaces approximating the corneal topography

NASA Astrophysics Data System (ADS)

Kasprzak, Henryk T.

1998-10-01

The first part of the paper presents the analytical curves used to approximate the corneal profile. Next, some definition of 3D surfaces curvature, like main normal sections, main radii of curvature and their orientations are given. The examples of four nonrotational 3D surfaces such as: ellipsoidal, surface based on hyperbolic cosine function, sphero-cylindrical and toroidal, approximating the corneal topography are proposed. The 3D surface and the contour plots of main radii of curvature and their orientation for four nonrotational approximation of the cornea are shown. Results of calculations are discussed from the point of view of videokeratometric images.

Scleral Shape and Its Correlations With Corneal Astigmatism.

PubMed

Consejo, Alejandra; Rozema, Jos J

2018-03-06

To assess the correlation between the scleral shape and corneal astigmatism. Twenty-two participants (11 nonastigmatic and 11 astigmatic) aged from 19 to 36 years and with no previous ocular surgeries were included in this study. Three-dimensional (3D) corneoscleral maps from both eyes (44 eyes) were acquired using a corneoscleral topographer (Eye Surface Profiler). Each 3D map was split into 13 concentric annuli, each 0.5-mm wide, starting at 1.0-mm radius from the corneal apex to the scleral periphery at 7.5 mm from the apex. Each ring was fitted to a quadratic function of the radial distance to the apex, to calculate the elevation difference between the raw data and the fitting surface ring. For each ring, the resulting elevation difference between the original and fit data profile was fit to a sum of sine function. Decentration and astigmatic terms obtained from the sinusoidal fit were analyzed and compared between nonastigmatic and astigmatic groups. In astigmatic eyes, corneal and scleral asymmetry are highly correlated, but both appear independent of each other in nonastigmatic eyes. No significant difference between astigmatic and nonastigmatic eyes was found for the decentration term [P > 0.05/N (Bonferroni)], whereas for the astigmatic component, the differences were statistically significant [P < 0.05/N (Bonferroni)]. Corneal and scleral shapes are correlated in astigmatic eyes, which suggests that astigmatism is not restricted to the cornea but should rather be considered a property of the entire eye globe.

Co-ordinated ocular development from human iPS cells and recovery of corneal function.

PubMed

Hayashi, Ryuhei; Ishikawa, Yuki; Sasamoto, Yuzuru; Katori, Ryosuke; Nomura, Naoki; Ichikawa, Tatsuya; Araki, Saori; Soma, Takeshi; Kawasaki, Satoshi; Sekiguchi, Kiyotoshi; Quantock, Andrew J; Tsujikawa, Motokazu; Nishida, Kohji

2016-03-17

The eye is a complex organ with highly specialized constituent tissues derived from different primordial cell lineages. The retina, for example, develops from neuroectoderm via the optic vesicle, the corneal epithelium is descended from surface ectoderm, while the iris and collagen-rich stroma of the cornea have a neural crest origin. Recent work with pluripotent stem cells in culture has revealed a previously under-appreciated level of intrinsic cellular self-organization, with a focus on the retina and retinal cells. Moreover, we and others have demonstrated the in vitro induction of a corneal epithelial cell phenotype from pluripotent stem cells. These studies, however, have a single, tissue-specific focus and fail to reflect the complexity of whole eye development. Here we demonstrate the generation from human induced pluripotent stem cells of a self-formed ectodermal autonomous multi-zone (SEAM) of ocular cells. In some respects the concentric SEAM mimics whole-eye development because cell location within different zones is indicative of lineage, spanning the ocular surface ectoderm, lens, neuro-retina, and retinal pigment epithelium. It thus represents a promising resource for new and ongoing studies of ocular morphogenesis. The approach also has translational potential and to illustrate this we show that cells isolated from the ocular surface ectodermal zone of the SEAM can be sorted and expanded ex vivo to form a corneal epithelium that recovers function in an experimentally induced animal model of corneal blindness.

N-Isopropylacrylamide-co-glycidylmethacrylate as a Thermoresponsive Substrate for Corneal Endothelial Cell Sheet Engineering

PubMed Central

Madathil, Bernadette K.; Anil Kumar, Pallickaveedu RajanAsari; Kumary, Thrikkovil Variyath

2014-01-01

Endothelial keratoplasty is a recent shift in the surgical treatment of corneal endothelial dystrophies, where the dysfunctional endothelium is replaced whilst retaining the unaffected corneal layers. To overcome the limitation of donor corneal shortage, alternative use of tissue engineered constructs is being researched. Tissue constructs with intact extracellular matrix are generated using stimuli responsive polymers. In this study we evaluated the feasibility of using the thermoresponsive poly(N-isopropylacrylamide-co-glycidylmethacrylate) polymer as a culture surface to harvest viable corneal endothelial cell sheets. Incubation below the lower critical solution temperature of the polymer allowed the detachment of the intact endothelial cell sheet. Phase contrast and scanning electron microscopy revealed the intact architecture, cobble stone morphology, and cell-to-cell contact in the retrieved cell sheet. Strong extracellular matrix deposition was also observed. The RT-PCR analysis confirmed functionally active endothelial cells in the cell sheet as evidenced by the positive expression of aquaporin 1, collagen IV, Na+-K+ ATPase, and FLK-1. Na+-K+ ATPase protein expression was also visualized by immunofluorescence staining. These results suggest that the in-house developed thermoresponsive culture dish is a suitable substrate for the generation of intact corneal endothelial cell sheet towards transplantation for endothelial keratoplasty. PMID:25003113

Autophagy in the eye: implications for ocular cell health.

PubMed

Frost, Laura S; Mitchell, Claire H; Boesze-Battaglia, Kathleen

2014-07-01

Autophagy, a catabolic process by which a cell "eats" itself, turning over its own cellular constituents, plays a key role in cellular homeostasis. In an effort to maintain normal cellular function, autophagy is often up-regulated in response to environmental stresses and excessive organelle damage to facilitate aggregated protein removal. In the eye, virtually all cell types from those comprising the cornea in the front of the eye to the retinal pigment epithelium (RPE) providing a protective barrier for the retina at the back of the eye, rely on one or more aspects of autophagy to maintain structure and/or normal physiological function. In the lens autophagy plays a critical role in lens fiber cell maturation and the formation of the organelle free zone. Numerous studies delineating the role of Atg5, Vsp34 as well as FYCO1 in maintenance of lens transparency are discussed. Corneal endothelial dystrophies are also characterized as having elevated levels of autophagic proteins. Therefore, novel modulators of autophagy such as lithium and melatonin are proposed as new therapeutic strategies for this group of dystrophies. In addition, we summarize how corneal Herpes Simplex Virus (HSV-1) infection subverts the cornea's response to infection by inhibiting the normal autophagic response. Using glaucoma models we analyze the relative contribution of autophagy to cell death and cell survival. The cytoprotective role of autophagy is further discussed in an analysis of photoreceptor cell heath and function. We focus our analysis on the current understanding of autophagy in photoreceptor and RPE health, specifically on the diverse role of autophagy in rods and cones as well as its protective role in light induced degeneration. Lastly, in the RPE we highlight hybrid phagocytosis-autophagy pathways. This comprehensive review allows us to speculate on how alterations in various stages of autophagy contribute to glaucoma and retinal degenerations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Nitrogen mustard-induced corneal injury involves DNA damage and pathways related to inflammation, epithelial-stromal separation and neovascularization

PubMed Central

Goswami, Dinesh G; Tewari-Singh, Neera; Dhar, Deepanshi; Kumar, Dileep; Agarwal, Chapla; Ammar, David A; Kant, Rama; Enzenauer, Robert W; Petrash, J Mark; Agarwal, Rajesh

2015-01-01

Purpose To evaluate the toxic effects and associated mechanisms in corneal tissue exposed to vesicating agent, nitrogen mustard (NM), a bi-functional alkylating analog of chemical warfare agent sulfur mustard (SM). Methods Toxic effects and associated mechanisms were examined in maximal affected corneal tissue employing corneal cultures and human corneal epithelial (HCE) cells exposed to nitrogen mustard (NM). Results Analysis of ex vivo rabbit corneas showed that NM exposure increased apoptotic cell death, epithelial thickness, epithelial-stromal separation and levels of VEGF, COX-2 and MMP-9. In HCE cells, NM exposure resulted in a dose-dependent decrease in cell viability and proliferation, which was associated with DNA damage in terms of an increase in p53 ser15, total p53 and H2A.X ser139 levels. NM exposure also induced caspase-3 and PARP cleavage, suggesting their involvement in NM-induced apoptotic death in rabbit cornea and HCE cells. Similar to rabbit cornea, NM exposure caused an increase in COX-2, MMP-9 and VEGF levels in HCE cells, indicating a role of these molecules and related pathways in NM-induced corneal inflammation, epithelial-stromal separation and neovascularization. NM exposure also induced activation of AP-1 transcription factor proteins and upstream signaling pathways including MAPKs and Akt, suggesting that these could be key factors involved in NM-induced corneal injury. Conclusion Results from this study provide insight into the molecular targets and pathways that could be involved in NM-induced corneal injuries laying the background for further investigation of these pathways in vesicant–induced ocular injuries, which could be helpful in the development of targeted therapies. PMID:26555588

Biomechanical Strengthening of the Human Cornea Induced by Nanoplatform-Based Transepithelial Riboflavin/UV-A Corneal Cross-Linking.

PubMed

Labate, Cristina; Lombardo, Marco; Lombardo, Giuseppe; De Santo, Maria Penelope

2017-01-01

The purpose of this study was to investigate the biomechanical stiffening effect induced by nanoplatform-based transepithelial riboflavin/UV-A cross-linking protocol using atomic force microscopy (AFM). Twelve eye bank donor human sclerocorneal tissues were investigated using a commercial atomic force microscope operated in force spectroscopy mode. Four specimens underwent transepithelial corneal cross-linking using a hypotonic solution of 0.1% riboflavin with biodegradable polymeric nanoparticles of 2-hydroxypropyl-β-cyclodextrin plus enhancers (trometamol and ethylenediaminetetraacetic acid) and UV-A irradiation with a 10 mW/cm2 device for 9 minutes. After treatment, the corneal epithelium was removed using the Amoils brush, and the Young's modulus of the most anterior stroma was quantified as a function of scan rate by AFM. The results were compared with those collected from four specimens that underwent conventional riboflavin/UV-A corneal cross-linking and four untreated specimens. The average Young's modulus of the most anterior stroma after the nanoplatform-based transepithelial and conventional riboflavin/UV-A corneal cross-linking treatments was 2.5 times (P < 0.001) and 1.7 times (P < 0.001) greater than untreated controls respectively. The anterior stromal stiffness was significantly different between the two corneal cross-linking procedures (P < 0.001). The indentation depth decreased after corneal cross-linking treatments, ranging from an average of 2.4 ± 0.3 μm in untreated samples to an average of 1.2 ± 0.1 μm and 1.8 ± 0.1 μm after nanoplatform-based transepithelial and conventional cross-linking, respectively. The present nanotechnology-based transepithelial riboflavin/UV-A corneal cross-linking was effective to improve the biomechanical strength of the most anterior stroma of the human cornea.

Variable corneal compensation improves discrimination between normal and glaucomatous eyes with the scanning laser polarimeter.

PubMed

Tannenbaum, Dana P; Hoffman, Douglas; Lemij, Hans G; Garway-Heath, David F; Greenfield, David S; Caprioli, Joseph

2004-02-01

The presently available scanning laser polarimeter (SLP) has a fixed corneal compensator (FCC) that neutralizes corneal birefringence only in eyes with birefringence that matches the population mode. A prototype variable corneal compensator (VCC) provides neutralization of individual corneal birefringence based on individual macular retardation patterns. The aim of this study was to evaluate the relative ability of the SLP with the FCC and with the VCC to discriminate between normal and glaucomatous eyes. Prospective, nonrandomized, comparative case series. Algorithm-generating set consisting of 56 normal eyes and 55 glaucomatous eyes and an independent data set consisting of 83 normal eyes and 56 glaucomatous eyes. Sixteen retardation measurements were obtained with the SLP with the FCC and the VCC from all subjects. Dependency of parameters on age, gender, ethnic origin, and eye side was sought. Logistic regression was used to evaluate how well the various parameters could detect glaucoma. Discriminant functions were generated, and the area under the receiver operating characteristic (ROC) curve was determined. Discrimination between normal and glaucomatous eyes on the basis of single parameters was significantly better with the VCC than with the FCC for 6 retardation parameters: nasal average (P = 0.0003), superior maximum (P = 0.0003), ellipse average (P = 0.002), average thickness (P = 0.003), superior average (P = 0.010), and inferior average (P = 0.010). Discriminant analysis identified the optimal combination of parameters for the FCC and for the VCC. When the discriminant functions were applied to the independent data set, areas under the ROC curve were 0.84 for the FCC and 0.90 for the VCC (P<0.021). When the discriminant functions were applied to a subset of patients with early visual field loss, areas under the ROC curve were 0.82 for the FCC and 0.90 for the VCC (P<0.016). Individual correction for corneal birefringence with the VCC significantly improved the ability of the SLP to distinguish between normal and glaucomatous eyes and enabled detection of patients with early glaucoma.

Role of Corneal Stromal Cells on Epithelial Cell Function during Wound Healing

PubMed Central

Kowtharapu, Bhavani S.; Murín, Radovan; Jünemann, Anselm G. M.; Stachs, Oliver

2018-01-01

Following injury, corneal stromal keratocytes transform into repair-phenotype of activated stromal fibroblasts (SFs) and participate in wound repair. Simultaneously, ongoing bi-directional communications between corneal stromal-epithelial cells also play a vital role in mediating the process of wound healing. Factors produced by stromal cells are known to induce proliferation, differentiation, and motility of corneal epithelial cells, which are also subsequently the main processes that occur during wound healing. In this context, the present study aims to investigate the effect of SFs conditioned medium (SFCM) on corneal epithelial cell function along with substance P (SP). Antibody microarrays were employed to profile differentially expressed cell surface markers and cytokines in the presence of SFCM and SP. Antibody microarray data revealed enhanced expression of the ITGB1 in corneal epithelial cells following stimulation with SP whereas SFCM induced abundant expression of IL-8, ITGB1, PD1L1, PECA1, IL-15, BDNF, ICAM1, CD8A, CD44 and NTF4. All these proteins have either direct or indirect roles in epithelial cell growth, movement and adhesion related signaling cascades during tissue regeneration. We also observed activation of MAPK signaling pathway along with increased expression of focal adhesion kinase (FAK), paxillin, vimentin, β-catenin and vasodilator-stimulated phosphoprotein (VASP) phosphorylation. Additionally, epithelial-to-mesenchymal transition (EMT) regulating transcription factors Slug and ZEB1 expression were enhanced in the presence of SFCM. SP enriched the expression of integrin subunits α4, α5, αV, β1 and β3 whereas SFCM increased α4, α5, αV, β1 and β5 integrin subunits. We also observed increased expression of Serpin E1 following SP and SFCM treatment. Wound healing scratch assay revealed enhanced migration of epithelial cells following the addition of SFCM. Taken together, we conclude that SFCM-mediated sustained activation of ZEB1, Slug in combination with upregulated migration-associated integrins and ERK (Extracellular signal-regulated kinase)-FAK-paxillin axis, may lead to induce type 2 EMT-like changes during corneal epithelial wound healing. PMID:29401709

Association of Body Length with Ocular Parameters in Mice

PubMed Central

Chakraborty, Ranjay; Park, Han na; Tan, Christopher C.; Weiss, Paul; Prunt, Megan C.; Pardue, Machelle T.

2017-01-01

Purpose To determine the association between changes in body length with ocular refraction, corneal radii, axial length, and lens thickness in two different mouse strains. Methods Body length, ocular refraction, corneal radii, axial length, and lens thickness were measured for two inbred mouse strains: 129S1/SvJ (n=7) and C57BL/6J (n=10) from 4 to 12 weeks of age. Body length, from tip of nose to base of tail was obtained using a digital camera. Biometric parameters, corneal radii and refractions were measured using spectral-domain optical coherence tomography, automated keratometry and infrared photorefraction, respectively. A mixed model ANOVA was performed to examine the changes in ocular parameters as a function of body length and strain in mice controlling for age, gender and weight over time. Results C57BL/6J mice had significantly longer body length (average body length at 10 weeks, 8.60 ± 0.06 cm) compared 129S1/SvJ mice (8.31 ± 0.05 cm) during development (p<0.001). C57BL/6J mice had significantly hyperopic refractions compared to 129S1/SvJ mice across age (mean refraction at 10 weeks, 129S1/SvJ: +0.99 ± 0.44 D versus C57BL/6J: +6.24 ± 0.38 D, p<0.001). Corneal radius of curvature, axial length and lens thickness (except 10 weeks lens thickness) were similar between the two strains throughout the measurement. In the mixed model ANOVA, changes in body length showed an independent and significant association with the changes in refraction (p=0.002) and corneal radii (p=0.016) for each mouse strain. No significant association was found between the changes in axial length (p=0.925) or lens thickness (p=0.973) as a function of body length and strain. Conclusions Changes in body length are significantly associated with the changes in ocular refraction and corneal radii in different mouse strains. Future studies are needed to determine if the association between body length and ocular refraction are related to changes in corneal curvature in mice. PMID:28005683

Mitigating Scarring and Inflammation during Corneal Wound Healing using Nanofiber-Hydrogel Scaffolds

NASA Astrophysics Data System (ADS)

Fu, Amy

Due to the universal lack of donor tissue, there has been emerging interest in engineering materials to stimulate living cells to restore the features and functions of injured organs. We are particularly interested in developing materials for corneal use, where the necessity to maintain the tissue's transparency presents an additional challenge. Every year, there are 1.5 -- 2 million new cases of monocular blindness due to irregular healing of corneal injuries, dwarfing the approximately 150,000 corneal transplants performed. The large gap between the need and availability of cornea transplantation motivates us to develop a wound-healing scaffold that can prevent corneal blindness. To develop such a scaffold, it is necessary to regulate the cells responsible for repairing the damaged cornea, namely myofibroblasts, which are responsible for the disordered and non-refractive index matched scar that leads to corneal blindness. Using in vitro assays, we identified that protein nanofibers of certain orientation can promote cell migration and modulate the myofibroblast phenotype. The nanofibers are also transparent, easy to handle and non-cytotoxic. To adhere the nanofibers to a wound bed, we examined the use of two different in situ forming hydrogels: an artificial extracellular matrix protein (aECM)-based gel and a photo-crosslinkable heparin-based gel. Both hydrogels can be formed within minutes, are transparent upon gelation and are easily tunable. Using an in vivo mouse model for epithelial defects, we show that our corneal scaffolds (nanofibers together with hydrogel) are well-tolerated (no inflammatory response or turbidity) and support epithelium regrowth. We developed an ex vivo corneal tissue culture model where corneas that are wounded and treated with our scaffold can be cultured while retaining their ability to repair wounds for up to 21 days. Using this technique, we found that the aECM-based treatment induced a more favorable wound response than the heparin-based treatment, prompting us to further examine the efficacy of the aECM-based treatment in vivo using a rabbit model for stromal wounds. Results show that treated corneas have fewer myofibroblasts and immune cells than untreated ones, indicating that our corneal scaffold shows promise in promoting a calmer wound response and preventing corneal haze formation.

Relationship between Scanning Laser Polarimetry with Enhanced Corneal Compensation and with Variable Corneal Compensation

PubMed Central

Kim, Kyung Hoon; Choi, Jaewan; Lee, Chang Hwan; Cho, Beom-Jin; Kook, Michael S.

2008-01-01

Purpose To evaluate the structure-function relationships between retinal sensitivity measured by Humphrey visual field analyzer (HVFA) and the retinal nerve fiber layer (RNFL) thickness measured by scanning laser polarimetry (SLP) with variable corneal compensation (VCC) and enhanced corneal compensation (ECC) in glaucomatous and healthy eyes. Methods Fifty-three eyes with an atypical birefringence pattern (ABP) based on SLP-VCC (28 glaucomatous eyes and 25 normal healthy eyes) were enrolled in this cross-sectional study. RNFL thickness was measured by both VCC and ECC techniques, and the visual field was examined by HVFA with 24-2 full-threshold program. The relationships between RNFL measurements in superior and inferior sectors and corresponding retinal mean sensitivity were sought globally and regionally with linear regression analysis in each group. Coefficients of the determination were calculated and compared between VCC and ECC techniques. Results In eyes with ABP, R2 values for the association between SLP parameters and retinal sensitivity were 0.06-0.16 with VCC, whereas they were 0.21-0.48 with ECC. The association of RNFL thickness with retinal sensitivity was significantly better with ECC than with VCC in 5 out of 8 regression models between SLP parameters and HVF parameters (P<0.05). Conclusions The strength of the structure-function association was higher with ECC than with VCC in eyes with ABP, which suggests that the ECC algorithm is a better approach for evaluating the structure-function relationship in eyes with ABP. PMID:18323701

Functional optical zone of the cornea.

PubMed

Tabernero, Juan; Klyce, Stephen D; Sarver, Edwin J; Artal, Pablo

2007-03-01

When keratorefractive surgery is used to treat a central corneal diameter smaller than the resting pupil, visual symptoms of polyopia, ghosting, blur, haloes, and glare can be experienced. Progress has been made to enlarge the area of surgical treatment to extend beyond the photopic pupil; however, geometric limitations can pose restrictions to extend the treatment beyond the mesopic pupil diameter and can lead to impediments in night vision. The size of the treated area that has achieved good optical performance has been defined as the functional optical zone (FOZ). In this study the authors developed three objective methods to measure the FOZ. Corneal topography examination results from 1 eye of 34 unoperated normal eyes and 32 myopic eyes corrected by laser in situ keratomileusis (LASIK) were evaluated in three ways. First, a uniform axial power method (FOZ(A)) assessed the area of the postoperative cornea that was within a +/-0.5-D window centered on the mathematical mode. Second, FOZ was determined based on the corneal wavefront true RMS error as a function of the simulated pupil size (FOZ(R)). Third, FOZ was determined from the radial MTF, established at the retinal plane as a function of pupil size (FOZ(M)). Means for each of the FOZ methods (FOZ(A), FOZ(R), and FOZ(M)) were 7.6, 9.1, and 7.7 mm, respectively, for normal eyes. For LASIK-corrected eyes, these means were 6.0, 6.9, and 6.0 mm. Overall, an average decrease of 1.8 mm in the functional optical zone was found after the LASIK procedure. Correlations between the FOZ methods after LASIK showed acceptable and statistically significant values (R = 0.71, 0.70, and 0.61; P < 0.01). These methods will be useful to more fully characterize corneal treatment profiles after keratorefractive surgery. Because of its ease of implementation, direct spatial correspondence to corneal topography, and good correlation to the other more computationally intensive methods, the semiempiric uniform axial power method (FOZ(A)) appears to be most practical in use. The ability to measure the size of the FOZ should permit further evolution of keratorefractive surgical lasers and their algorithms to reduce the night vision impediments that can arise from functional optical zones that do not encompass the entire mesopic pupil.

Response of human corneal fibroblasts on silk film surface patterns.

PubMed

Gil, Eun Seok; Park, Sang-Hyug; Marchant, Jeff; Omenetto, Fiorenzo; Kaplan, David L

2010-06-11

Transparent, biodegradable, mechanically robust, and surface-patterned silk films were evaluated for the effect of surface morphology on human corneal fibroblast (hCF) cell proliferation, orientation, and ECM deposition and alignment. A series of dimensionally different surface groove patterns were prepared from optically graded glass substrates followed by casting poly(dimethylsiloxane) (PDMS) replica molds. The features on the patterned silk films showed an array of asymmetric triangles and displayed 37-342 nm depths and 445-3 582 nm widths. hCF DNA content on all patterned films were not significantly different from that on flat silk films after 4 d in culture. However, the depth and width of the grooves influenced cell alignment, while the depth differences affected cell orientation; overall, deeper and narrower grooves induced more hCF orientation. Over 14 d in culture, cell layers and actin filament organization demonstrated that confluent hCFs and their cytoskeletal filaments were oriented along the direction of the silk film patterned groove axis. Collagen type V and proteoglycans (decorin and biglycan), important markers of corneal stromal tissue, were highly expressed with alignment. Understanding corneal stromal fibroblast responses to surface features on a protein-based biomaterial applicable in vivo for corneal repair potential suggests options to improve corneal tissue mimics. Further, the approaches provide fundamental biomaterial designs useful for bioengineering oriented tissue layers, an endemic feature in most biological tissue structures that lead to critical tissue functions.

Lumican Peptides: Rational Design Targeting ALK5/TGFBRI

NASA Astrophysics Data System (ADS)

Gesteira, Tarsis Ferreira; Coulson-Thomas, Vivien J.; Yuan, Yong; Zhang, Jianhua; Nader, Helena B.; Kao, Winston W.-Y.

2017-02-01

Lumican, a small leucine rich proteoglycan (SLRP), is a component of extracellular matrix which also functions as a matrikine regulating multiple cell activities. In the cornea, lumican maintains corneal transparency by regulating collagen fibrillogenesis, promoting corneal epithelial wound healing, regulating gene expression and maintaining corneal homeostasis. We have recently shown that a peptide designed from the 13 C-terminal amino acids of lumican (LumC13) binds to ALK5/TGFBR1 (type1 receptor of TGFβ) to promote wound healing. Herein we evaluate the mechanism by which this synthetic C-terminal amphiphilic peptide (LumC13), binds to ALK5. These studies clearly reveal that LumC13-ALK5 form a stable complex. In order to determine the minimal amino acids required for the formation of a stable lumican/ALK5 complex derivatives of LumC13 were designed and their binding to ALK5 investigated in silico. These LumC13 derivatives were tested both in vitro and in vivo to evaluate their ability to promote corneal epithelial cell migration and corneal wound healing, respectively. These validations add to the therapeutic value of LumC13 (Lumikine) and aid its clinical relevance of promoting the healing of corneal epithelium debridement. Moreover, our data validates the efficacy of our computational approach to design active peptides based on interactions of receptor and chemokine/ligand.

Nerve growth factor effect on human primary fibroblastic-keratocytes: possible mechanism during corneal healing.

PubMed

Micera, Alessandra; Lambiase, Alessandro; Puxeddu, Ilaria; Aloe, Luigi; Stampachiacchiere, Barbara; Levi-Schaffer, Francesca; Bonini, Sergio; Bonini, Stefano

2006-10-01

In response to corneal injury, cytokines and growth factors play a crucial role by influencing epithelial-stromal interaction during the healing and reparative processes which may resolve in tissue remodeling and fibrosis. While transforming growth factor-beta1 (TGF-beta1) is considered the main profibrogenic modulator of these process, recently the nerve growth factor (NGF) appears as a pleiotropic modulator of wound-healing and inflammatory responses. Interestingly in the cornea, where NGF, trkA(NGFR) and p75(NTR) are expressed by epithelial cells and keratocytes, the NGF eye-drop induces the healing of neurotrophic or autoimmune corneal ulcers. During corneal healing, quiescent keratocytes are replaced by active fibroblast-like keratocytes/myofibroblasts. While the NGF effect on epithelial cells has been investigated, no data are reported for NGF effects on fibroblastic-keratocytes, during corneal healing. NGF, trkA(NGFR) and p75(NTR) were found expressed by fibroblastic-keratocytes. NGF was able to induce fibroblastic-keratocyte differentiation into myofibroblasts, migration, Metalloproteinase-9 expression/activity and contraction of a 3D collagen gel, without affecting their proliferation and collagen production. These data also show a two-directional control of fibroblastic-keratocytes by NGF and TGF-beta1. To sum up, the findings of this study indicate that NGF can modulate some functional activities of fibroblastic-keratocytes, thus substantiating the healing effects of NGF on corneal wound-healing.

Inhibition by rebamipide of cytokine-induced or lipopolysaccharide-induced chemokine synthesis in human corneal fibroblasts.

PubMed

Fukuda, Ken; Ishida, Waka; Tanaka, Hiroshi; Harada, Yosuke; Fukushima, Atsuki

2014-12-01

The dry-eye drug rebamipide has mucin secretagogue activity in and anti-inflammatory effects on corneal epithelial cells. Corneal stromal fibroblasts (transdifferentiated keratocytes) function as immune modulators in the pathogenesis of chronic ocular allergic inflammation and in innate immune responses at the ocular surface. The possible anti-inflammatory effects of rebamipide on human corneal stromal fibroblasts were examined. Serum-deprived cells were incubated for 1 h with rebamipide and then for various times in the additional absence or presence of cytokines or bacterial lipopolysaccharide (LPS). The release of chemokines into culture supernatants was determined with ELISAs. The intracellular abundance of chemokine mRNAs was quantitated by reverse transcription and real-time PCR analysis. Degradation of the nuclear factor κB (NFκB) inhibitor IκBα was detected by immunoblot analysis. Rebamipide suppressed the release of interleukin (IL)-8 and the upregulation of IL-8 mRNA induced by tumour necrosis factor α (TNF-α) or LPS in corneal fibroblasts. It also inhibited eotaxin-1 (CCL-11) expression at the protein and mRNA levels induced by the combination of TNF-α and IL-4. In addition, rebamipide attenuated the degradation of IκBα induced by TNF-α or LPS. Rebamipide inhibited the synthesis of chemokines by corneal fibroblasts in association with suppression of NFκB signalling. Rebamipide may therefore prove effective for the treatment of corneal stromal inflammation associated with allergy or bacterial infection. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

New pinhole sulcus implant for the correction of irregular corneal astigmatism.

PubMed

Trindade, Claudio C; Trindade, Bruno C; Trindade, Fernando C; Werner, Liliana; Osher, Robert; Santhiago, Marcony R

2017-10-01

To evaluate the effect on visual acuity of the implantation of a new intraocular pinhole device (Xtrafocus) in cases of irregular corneal astigmatism with significant visual impairment. University of São Paulo, São Paulo, Brazil. Prospective case series. Pseudophakic eyes of patients with irregular corneal astigmatism were treated with the pinhole device. The causes of irregular corneal astigmatism were keratoconus, post radial keratotomy (RK), post-penetrating keratoplasty (PKP), and traumatic corneal laceration. The device was implanted in the ciliary sulcus in a piggyback configuration to minimize the effect of corneal aberrations. Preoperative and postoperative visual parameters were compared. The main outcome variables were manifest refraction, uncorrected and corrected distance and near visual acuities, subjective patient satisfaction, and intraoperative and postoperative adverse events and complications. Twenty-one patients (ages 35 to 85 years) were included. There was statistically significant improvement in uncorrected and corrected (CDVA) distance visual acuities. The median CDVA improved from 20/200 (range 20/800 to 20/60) preoperatively to 20/50 (range 20/200 to 20/20) in the first month postoperatively and remained stable over the following months. Manifest refraction remained unchanged, while a subjective visual performance questionnaire revealed perception of improvement in all the tested working distances. No major complication was observed. One case presented with decentration of the device, which required an additional surgical intervention. The intraocular pinhole device performed well in patients with irregular astigmatism caused by keratoconus, RK, PKP, and traumatic corneal laceration. There was marked improvement in visual function, with high patient satisfaction. Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Optical modeling of a corneal inlay in real eyes to increase depth of focus: optimum centration and residual defocus.

PubMed

Tabernero, Juan; Artal, Pablo

2012-02-01

To determine the optimum position to center a small-aperture corneal inlay and the effect of residual defocus in the surgical eye to maximize depth of focus. Laboratorio de Óptica, Universidad de Murcia, Murcia, Spain. Cohort study. Personalized eye models were built using actual data (corneal topography, eye length, ocular aberrations, and eye alignment). A small aperture 1.6 mm in diameter was placed at the corneal plane in each model. The monochromatic and polychromatic Strehl ratios were calculated as a function of the pinhole position. Different residual defocus values were also incorporated into the models, and the through-focus Strehl ratios were calculated. Sixteen eye models were built. For most subjects, the optimum location of the aperture for distance vision was close to the corneal reflex position. For a given optimized centration of the aperture, the best compromise of depth of focus was obtained when the eyes had some residual myopic defocus (range -0.75 to -1.00 diopter [D]). Strehl ratio values were over 0.1 for far distance, which led to visual acuities better than 20/20. The depth of focus was 2.50 D with a mean near visual acuity of Jaeger 1 or better. In eyes with little astigmatism and aberrations, the optimum centration of the small aperture was near the corneal reflex position. To improve optical outcomes with the inlay, some small residual myopia and correction of corneal astigmatism might be required. Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Confocal microscopy and electrophysiological study of single patient corneal endothelium cell cultures

NASA Astrophysics Data System (ADS)

Tatini, Francesca; Rossi, Francesca; Coppi, Elisabetta; Magni, Giada; Fusco, Irene; Menabuoni, Luca; Pedata, Felicita; Pugliese, Anna Maria; Pini, Roberto

2016-04-01

The characterization of the ion channels in corneal endothelial cells and the elucidation of their involvement in corneal pathologies would lead to the identification of new molecular target for pharmacological treatments and to the clarification of corneal physiology. The corneal endothelium is an amitotic cell monolayer with a major role in preserving corneal transparency and in regulating the water and solute flux across the posterior surface of the cornea. Although endothelial cells are non-excitable, they express a range of ion channels, such as voltage-dependent Na+ channels and K+ channels, L-type Ca2 channels and many others. Interestingly, purinergic receptors have been linked to a variety of conditions within the eye but their presence in the endothelium and their role in its pathophysiology is still uncertain. In this study, we were able to extract endothelial cells from single human corneas, thus obtaining primary cultures that represent the peculiarity of each donor. Corneas were from tissues not suitable for transplant in patients. We characterized the endothelial cells by confocal microscopy, both within the intact cornea and in the primary endothelial cells cultures. We also studied the functional role of the purinergic system (adenosine, ATP and their receptors) by means of electrophysiological recordings. The experiments were performed by patch clamp recordings and confocal time-lapse microscopy and our results indicate that the application of purinergic compounds modulates the amplitude of outward currents in the isolated endothelial cells. These findings may lead to the proposal of new therapies for endothelium-related corneal diseases.

A COMPREHENSIVE INSIGHT ON OCULAR PHARMACOKINETICS

PubMed Central

Agrahari, Vibhuti; Mandal, Abhirup; Agrahari, Vivek; Trinh, Hoang My; Joseph, Mary; Ray, Animikh; Hadji, Hicheme; Mitra, Ranjana; Pal, Dhananjay; Mitra, Ashim K.

2017-01-01

Eye is a distinctive organ with protective anatomy and physiology. Several pharmacokinetics compartment model of ocular drug delivery has been developed for describing the absorption, distribution and elimination of ocular drugs in the eye. Determining pharmacokinetics parameters in ocular tissues is a major challenge because of the complex anatomy and dynamic physiological barrier of the eye. In this review, pharmacokinetics of these compartments exploring different drugs, delivery systems and routes of administration are discussed including factors affecting intraocular bioavailability. Factors such as pre-corneal fluid drainage, drug binding to tear proteins, systemic drug absorption, corneal factors, melanin binding, drug metabolism renders ocular delivery challenging and elaborated in this manuscript. Several compartment models are discussed those are developed in ocular drug delivery to study the pharmacokinetics parameters. There are several transporters present in both anterior and posterior segments of the eye which play a significant role in ocular pharmacokinetics and summarized briefly. Moreover, several ocular pharmacokinetics animal models and relevant studies are reviewed and discussed in addition to the pharmacokinetics of various ocular formulations. PMID:27798766

Liposomes and nanotechnology in drug development: focus on ocular targets

PubMed Central

Honda, Miki; Asai, Tomohiro; Oku, Naoto; Araki, Yoshihiko; Tanaka, Minoru; Ebihara, Nobuyuki

2013-01-01

Poor drug delivery to lesions in patients’ eyes is a major obstacle to the treatment of ocular diseases. The accessibility of these areas to drugs is highly restricted by the presence of barriers, including the corneal barrier, aqueous barrier, and the inner and outer blood–retinal barriers. In particular, the posterior segment is difficult to reach for drugs because of its structural peculiarities. This review discusses various barriers to drug delivery and provides comprehensive information for designing nanoparticle-mediated drug delivery systems for the treatment of ocular diseases. Nanoparticles can be designed to improve penetration, controlled release, and drug targeting. As highlighted in this review, the therapeutic efficacy of drugs in ocular diseases has been reported to be enhanced by the use of nanoparticles such as liposomes, micro/nanospheres, microemulsions, and dendrimers. Our recent data show that intravitreal injection of targeted liposomes encapsulating an angiogenesis inhibitor caused significantly greater suppression of choroidal neovascularization than did the injection of free drug. Recent progress in ocular drug delivery systems research has provided new insights into drug development, and the use of nanoparticles for drug delivery is thus a promising approach for advanced therapy of ocular diseases. PMID:23439842

Lacritin and other new proteins of the lacrimal functional unit.

PubMed

McKown, Robert L; Wang, Ningning; Raab, Ronald W; Karnati, Roy; Zhang, Yinghui; Williams, Patricia B; Laurie, Gordon W

2009-05-01

The lacrimal functional unit (LFU) is defined by the 2007 International Dry Eye WorkShop as 'an integrated system comprising the lacrimal glands, ocular surface (cornea, conjunctiva and meibomian glands) and lids, and the sensory and motor nerves that connect them'. The LFU maintains a healthy ocular surface primarily through a properly functioning tear film that provides protection, lubrication, and an environment for corneal epithelial cell renewal. LFU cells express thousands of proteins. Over 200 new LFU proteins have been discovered in the last decade. Lacritin is a new LFU-specific growth factor in human tears that flows through ducts to target corneal epithelial cells on the ocular surface. When applied topically in rabbits, lacritin appears to increase the volume of basal tear secretion. Lacritin is one of only a handful of tear proteins preliminarily reported to be downregulated in blepharitis and in two dry eye syndromes. Computational analysis predicts an ordered C-terminal domain that binds the corneal epithelial cell surface proteoglycan syndecan-1 (SDC1) and is required for lacritin's low nanomolar mitogenic activity. The lacritin-binding site on the N-terminus of SDC1 is exposed by heparanase. Heparanase is constitutively expressed by the corneal epithelium and appears to be a normal constituent of tears. Binding triggers rapid signaling to downstream NFAT and mTOR. A wealth of other new proteins, originally designated as hypothetical when first identified by genomic sequencing, are expressed by the human LFU including: ALS2CL, ARHGEF19, KIAA1109, PLXNA1, POLG, WIPI1 and ZMIZ2. Their demonstrated or implied roles in human genetic disease or basic cellular functions are fuel for new investigation. Addressing topical areas in ocular surface physiology with new LFU proteins may reveal interesting new biological mechanisms and help get to the heart of ocular surface dysfunction.

Morphological and functional changes in TRPM8-expressing corneal cold thermoreceptor neurons during aging and their impact on tearing in mice.

PubMed

Alcalde, Ignacio; Íñigo-Portugués, Almudena; González-González, Omar; Almaraz, Laura; Artime, Enol; Morenilla-Palao, Cruz; Gallar, Juana; Viana, Félix; Merayo-Lloves, Jesús; Belmonte, Carlos

2018-08-01

Morphological and functional alterations of peripheral somatosensory neurons during the aging process lead to a decline of somatosensory perception. Here, we analyze the changes occurring with aging in trigeminal ganglion (TG), TRPM8-expressing cold thermoreceptor neurons innervating the mouse cornea, which participate in the regulation of basal tearing and blinking and have been implicated in the pathogenesis of dry eye disease (DED). TG cell bodies and axonal branches were examined in a mouse line (TRPM8 BAC -EYFP) expressing a fluorescent reporter. In 3 months old animals, about 50% of TG cold thermoreceptor neurons were intensely fluorescent, likely providing strongly fluorescent axons and complex corneal nerve terminals with ongoing activity at 34°C and low-threshold, robust responses to cooling. The remaining TRPM8 + corneal axons were weakly fluorescent with nonbeaded axons, sparsely ramified nerve terminals, and exhibited a low-firing rate at 34°C, responding moderately to cooling pulses as do weakly fluorescent TG neurons. In aged (24 months) mice, the number of weakly fluorescent TG neurons was strikingly high while the morphology of TRPM8 + corneal axons changed drastically; 89% were weakly fluorescent, unbranched, and often ending in the basal epithelium. Functionally, 72.5% of aged cold terminals responded as those of young animals, but 27.5% exhibited very low-background activity and abnormal responsiveness to cooling pulses. These morpho-functional changes develop in parallel with an enhancement of tear's basal flow and osmolarity, suggesting that the aberrant sensory inflow to the brain from impaired peripheral cold thermoreceptors contributes to age-induced abnormal tearing and to the high incidence of DED in elderly people. © 2018 Wiley Periodicals, Inc.

Management of a neurotrophic deep corneal ulcer with amniotic membrane transplantation in a patient with functional monocular vision

PubMed Central

Röck, Tobias; Bartz-Schmidt, Karl Ulrich; Röck, Daniel

2017-01-01

Abstract Rationale: Amniotic membrane transplantation (AMT) has been performed therapeutically in humans for over 100 years. In recent 2 decades AMTs have been used increasingly and successfully to treat various types of ophthalmic indications. Patient concerns: An 83-year-old man was referred to our eye hospital with a refractory neurotrophic deep corneal ulcer of the left eye. Diagnoses: The best-corrected visual acuity of the left eye was 0.5 (0.3 logMAR) and of the right eye was 0.05 (1.3 logMAR), which was caused by a central retinal vein occlusion 5 years previously. In cases of binocular vision, a large amniotic membrane patch can cover the whole cornea, including the optical axis. However, in cases with functional monocular vision, as in the case reported here, the AMT has to be performed without the involvement of the optical axis to ensure vision for the patient. Otherwise the patient would have a massively restricted view like looking through waxed paper for at least 2–4 weeks until the overlay dissolved. Interventions: For this case, an AMT using a modified sandwich technique was applied without involvement of the optic axis to ensure vision for the patient. This case report illustrates this eye's course of healing over time. Outcomes: A reduction in the inflammation and healing of the corneal ulcer could be seen. In addition, the corneal vascularization decreased. Six months after the AMT, a slit-lamp examination revealed stable findings. The best-corrected visual acuity of the left eye had increased to 0.8 (0.1 logMAR). Lessons: To the best of our knowledge, a case report on the management of a neurotrophic deep corneal ulcer with AMT in a patient with functional monocular vision has never been undertaken before. PMID:29390295

Multifunctional ion transport properties of human SLC4A11: comparison of the SLC4A11-B and SLC4A11-C variants.

PubMed

Kao, Liyo; Azimov, Rustam; Shao, Xuesi M; Frausto, Ricardo F; Abuladze, Natalia; Newman, Debra; Aldave, Anthony J; Kurtz, Ira

2016-11-01

Congenital hereditary endothelial dystrophy (CHED), Harboyan syndrome (CHED with progressive sensorineural deafness), and potentially a subset of individuals with late-onset Fuchs' endothelial corneal dystrophy are caused by mutations in the SLC4A11 gene that results in corneal endothelial cell abnormalities. Originally classified as a borate transporter, the function of SLC4A11 as a transport protein remains poorly understood. Elucidating the transport function(s) of SLC4A11 is needed to better understand how its loss results in the aforementioned posterior corneal dystrophic disease processes. Quantitative PCR experiments demonstrated that, of the three known human NH 2 -terminal variants, SLC4A11-C is the major transcript expressed in human corneal endothelium. We studied the expression pattern of the three variants in mammalian HEK-293 cells and demonstrated that the SLC4A11-B and SLC4A11-C variants are plasma membrane proteins, whereas SLC4A11-A is localized intracellularly. SLC4A11-B and SLC4A11-C were shown to be multifunctional ion transporters capable of transporting H + equivalents in both a Na + -independent and Na + -coupled mode. In both transport modes, SLC4A11-C H + flux was significantly greater than SLC4A11-B. In the presence of ammonia, SLC4A11-B and SLC4A11-C generated inward currents that were comparable in magnitude. Chimera SLC4A11-C-NH 2 -terminus-SLC4A11-B experiments demonstrated that the SLC4A11-C NH 2 -terminus functions as an autoactivating domain, enhancing Na + -independent and Na + -coupled H + flux without significantly affecting the electrogenic NH 3 -H (n) + cotransport mode. All three modes of transport were significantly impaired in the presence of the CHED causing p.R109H (SLC4A11-C numbering) mutation. These complex ion transport properties need to be addressed in the context of corneal endothelial disease processes caused by mutations in SLC4A11. Copyright © 2016 the American Physiological Society.

Cross-linking and the molecular packing of corneal collagen

NASA Technical Reports Server (NTRS)

Yamauchi, M.; Chandler, G. S.; Tanzawa, H.; Katz, E. P.

1996-01-01

We have quantitatively characterized, for the first time, the cross-linking in bovine cornea collagen as a function of age. The major iminium reducible cross-links were dehydro-hydroxylysinonorleucine (deH-HLNL) and dehydro-histidinohydroxymerodesmosine (deH-HHMD). The former rapidly diminished after birth; however, the latter persisted in mature animals at a level of 0.3 - 0.4 moles/mole of collagen. A nonreducible cross-link, histidinohydroxylysinonorleucine (HHL), previously found only in skin, was also found to be a major mature cross-link in cornea. The presence of HHL indicates that cornea fibrils have a molecular packing similar to skin collagen. However, like deH-HHMD, the HHL content in corneal fibrils only reaches a maximum value with time about half that of skin. These data suggest that the corneal fibrils are comprised of discrete filaments that are internally stabilized by HHL and deH-HHMD cross-links. This pattern of intermolecular cross-linking would facilitate the special collagen swelling property required for corneal transparency.

Using an ultrasound elasticity microscope to map three-dimensional strain in a porcine cornea.

PubMed

Hollman, Kyle W; Shtein, Roni M; Tripathy, Sakya; Kim, Kang

2013-08-01

An ultrasound elasticity microscope was used to map 3-D strain volume in an ex vivo porcine cornea to illustrate its ability to measure the mechanical properties of this tissue. Mechanical properties of the cornea play an important role in its function and, therefore, also in ophthalmic diseases such as kerataconus and corneal ectasia. The ultrasound elasticity microscope combines a tightly focused high-frequency transducer with confocal scanning to produce high-quality speckle over the entire volume of tissue. This system and the analysis were able to generate volume maps of compressional strain in all three directions for porcine corneal tissue, more information than any previous study has reported. Strain volume maps indicated features of the cornea and mechanical behavior as expected. These results constitute a step toward better understanding of corneal mechanics and better treatment of corneal diseases. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Influence of local inhomogeneities induced in corneal ablation on the evolution of contrast sensitivity

NASA Astrophysics Data System (ADS)

Ortiz, Dolores; Saiz, Jose M.; González, Francisco

2004-04-01

The presence of local inhomogeneities in corneal tissue after refractive surgery has an influence on visual performance. Here we focus on the corneal ablation associated with Lasik surgery and its effect on the modulation transfer function (MTF) that we obtained by modifying a personalized Kooijman model. Inhomogeneities induced by the ablation occur in the form of Gaussian-distributed refractive-index variations of a given correlation length. We show how variation of refractive-index deviation and correlation length (size) of the inhomogeneities allows us to obtain pairs of values that are able to achieve a MTF evolution similar to that observed for contrast sensitivity in the same patients. An estimate of the characteristics of the local effects is obtained.

Pediatric genetic disease of the cornea

PubMed Central

Fecarotta, Christopher M.; Huang, Wendy W.

2014-01-01

Our objective is to evaluate the literature regarding selected genetic diseases of the cornea, including megalocornea, keratoglobus, keratoconus, cystinosis, the mucopolysaccharidoses, sclerocornea, Peters' anomaly, familial dysautonomia, and various corneal dystrophies. The transparency of the cornea is a consequence of uniformity in both size and spacing of the collagen lamellae. The cornea's clarity depends on a delicate biochemical and structural balance; consequently, genetic disorders that disrupt either its metabolic or anatomic function can cause opacity and vision loss. Many childhood corneal diseases have a genetic etiology and are associated with known syndromes. Each disorder has unique associated set of possible complications. Prognosis often depends on the extent of opacity and disorganization of the anterior segment. Corneal transplantation has been performed for these disorders with variable success. PMID:27625877

Transactivation of involucrin, a marker of differentiation in keratinocytes, by lens epithelium-derived growth factor (LEDGF).

PubMed

Kubo, E; Fatma, N; Sharma, P; Shinohara, T; Chylack, L T; Akagi, Y; Singh, D P

2002-07-26

Human involucrin (hINV), first appears in the cytosol of keratinocytes and ultimately cross-linked to membrane proteins via transglutaminase and forms a protective barrier as an insoluble envelope beneath the plasma membrane. Although the function and evolution of involucrin is known, the regulation of its gene expression is not well understood. An analysis of the hINV gene sequence, upstream of the transcription start site (-534 to +1 nt) revealed the presence of potential sites for binding of lens epithelium-derived growth factor (LEDGF); stress response element (STRE; A/TGGGGA/T) and heat shock element (HSE; nGAAn). We reported earlier that LEDGF activates stress-associated genes by binding to these elements and elevates cellular resistance to various stresses. Here, gel-shift and super-shift assays confirm the binding of LEDGF to the DNA fragments containing HSEs and STREs that are present in the involucrin gene promoter. Furthermore, hINV promoter linked to CAT reporter gene, cotransfected in human corneal simian virus 40-transformed keratinocytes (HCK), was transactivated by LEDGF significantly. In contrast, the activity of hINV promoter bearing mutations at the WT1 (containing HSE and STRE), WT2 (containing STRE) and WT3 (containing STRE) binding sites was diminished. In addition, in HCK cell over-expressing LEDGF, the levels of hINV mRNA and hINV protein are increased by four to five-fold. LEDGF is inducible to oxidants. Cells treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), known to stimulate production of H(2)O(2), showed higher levels of LEDGF mRNA. Furthermore, our immunohistochemical studies revealed that hINV protein is found in the cytoplasm of HCK cells over-expressing LEDGF, but not detectable in the normal HCK cells or HCK cells transfected with vector. This regulation appears to be physiologically important, as over-expression of HCK with LEDGF increases the expression of the endogenous hINV gene and may provide new insight to understand the molecular mechanism of transcriptional regulation of this gene. LEDGF may play an important role in establishing an important barrier in corneal keratinocytes by maintaining epidermal turn-over rate, and protecting HCKs against stress.

Risk factors for corneal infiltrative events during continuous wear of silicone hydrogel contact lenses.

PubMed

Szczotka-Flynn, Loretta; Lass, Jonathan H; Sethi, Ajay; Debanne, Sara; Benetz, Beth Ann; Albright, Matthew; Gillespie, Beth; Kuo, Jana; Jacobs, Michael R; Rimm, Alfred

2010-11-01

This study determined which microbiologic, clinical, demographic, and behavioral factors are associated with corneal infiltrative events (CIEs) during continuous wear of silicone hydrogel (SH) contact lenses. Subjects (n = 205) were fitted with lotrafilcon A lenses for continuous wear and observed for 1 year. The main exposures of interest were corneal staining and bacterial lens contamination. Kaplan-Meier (KM) plots were used to estimate the cumulative unadjusted probability of remaining CIE free, and Cox proportional hazards regression was used to model the hazard of having a CIE, as a function of key predictor variables. The KM-unadjusted cumulative probability of remaining CIE free was 73.3%. Approximately 53% of subjects had repeated episodes of corneal staining (mild or greater), and 11.3% had repeated episodes of moderate or greater corneal staining. Corneal staining was not associated with the development of a CIE. The frequency of substantial bacterial bioburden on worn lenses at the time of a CIE was 64.7%, compared with only 12.2% during uncomplicated wear. The presence of substantial lens bacterial bioburden was associated with the development of a CIE (adjusted hazards ratio [HR], 8.66; 95% confidence interval [CI], 2.88-26.01). Smoking was also associated with a CIE (adjusted HR, 4.13; 95% CI, 1.27-13.45). Corneal staining is common during continuous wear of SH lenses, but it is not associated with the development of a CIE. Smoking and substantial lens bacterial bioburden pose prominent risks of a CIE. In this study, more than 70% of the total risk of CIE in those with substantial lens bioburden is attributable to this exposure. (ClinicalTrials.gov number, NCT00727402).

Spry1 and Spry2 Are Necessary for Lens Vesicle Separation and Corneal Differentiation

PubMed Central

Kuracha, Murali R.; Burgess, Daniel; Siefker, Ed; Cooper, Jake T.; Licht, Jonathan D.; Robinson, Michael L.

2011-01-01

Purpose. The studies reported here were performed to analyze the roles of Sproutys (Sprys), downstream targets and negative feedback regulators of the fibroblast growth factor (FGF) signaling pathway, in lens and corneal differentiation. Methods. Spry1 and -2 were conditionally deleted in the lens and corneal epithelial precursors using the Le-Cre transgene and floxed alleles of Spry1 and -2. Alterations in lens and corneal development were assessed by hematoxylin and eosin staining, in situ hybridization, and immunohistochemistry. Results. Spry1 and -2 were upregulated in the lens fibers at the onset of fiber differentiation. FGF signaling was both necessary and sufficient for induction of Spry1 and -2 in the lens fiber cells. Spry1 and -2 single- or double-null lenses failed to separate from the overlying ectoderm and showed persistent keratolenticular stalks. Apoptosis of stalk cells, normally seen during lens vesicle detachment from the ectoderm, was inhibited in Spry mutant lenses, with concomitant ERK activation. Prox1 and p57KIP2, normally upregulated at the onset of fiber differentiation were prematurely induced in the Spry mutant lens epithelial cells. However, terminal differentiation markers such as β- or γ-crystallin were not induced. Corneal epithelial precursors in Spry1 and -2 double mutants showed increased proliferation with elevated expression of Erm and DUSP6 and decreased expression of the corneal differentiation marker K12. Conclusions. Collectively, the results indicate that Spry1 and -2 (1) through negative modulation of ERKs allow lens vesicle separation, (2) are targets of FGF signaling in the lens during initiation of fiber differentiation and (3) function redundantly in the corneal epithelial cells to suppress proliferation. PMID:21743007

Inactivation of the miR-183/96/182 Cluster Decreases the Severity of Pseudomonas aeruginosa-Induced Keratitis

PubMed Central

Muraleedharan, Chithra K.; McClellan, Sharon A.; Barrett, Ronald P.; Li, Cui; Montenegro, Daniel; Carion, Thomas; Berger, Elizabeth; Hazlett, Linda D.; Xu, Shunbin

2016-01-01

Purpose The microRNA-183/96/182 cluster (miR-183/96/182) plays important roles in sensory organs. Because the cornea is replete with sensory innervation, we hypothesized that miR-183/96/182 modulates the corneal response to bacterial infection through regulation of neuroimmune interactions. Methods Eight-week-old miR-183/96/182 knockout (ko) mice and their wild-type littermates (wt) were used. The central cornea of anesthetized mice was scarred and infected with Pseudomonas aeruginosa (PA), strain 19660. Corneal disease was graded at 1, 3, and 5 days postinfection (dpi). Corneal RNA was harvested for quantitative RT-PCR. Polymorphonuclear neutrophils (PMN) were enumerated by myeloperoxidase assays; the number of viable bacteria was determined by plate counts, and ELISA assays were performed to determine cytokine protein levels. A macrophage (Mϕ) cell line and elicited peritoneal PMN were used for in vitro functional assays. Results MicroRNA-183/96/182 is expressed in the cornea, and in Mϕ and PMN of both mice and humans. Inactivation of miR-183/96/182 resulted in decreased corneal nerve density compared with wt mice. Overexpression of miR-183/96/182 in Mϕ decreased, whereas knockdown or inactivation of miR-183/96/182 in Mϕ and PMN increased their capacity for phagocytosis and intracellular killing of PA. In PA-infected corneas, ko mice showed decreased proinflammatory neuropeptides such as substance P and chemoattractant molecules, MIP-2, MCP1, and ICAM1; decreased number of PMN at 1 and 5 dpi; increased viable bacterial load at 1 dpi, but decreased at 5 dpi; and markedly decreased corneal disease. Conclusions MicroRNA-183/96/182 modulates the corneal response to bacterial infection through its regulation of corneal innervation and innate immunity. PMID:27035623

Inactivation of the miR-183/96/182 Cluster Decreases the Severity of Pseudomonas aeruginosa-Induced Keratitis.

PubMed

Muraleedharan, Chithra K; McClellan, Sharon A; Barrett, Ronald P; Li, Cui; Montenegro, Daniel; Carion, Thomas; Berger, Elizabeth; Hazlett, Linda D; Xu, Shunbin

2016-04-01

The microRNA-183/96/182 cluster (miR-183/96/182) plays important roles in sensory organs. Because the cornea is replete with sensory innervation, we hypothesized that miR-183/96/182 modulates the corneal response to bacterial infection through regulation of neuroimmune interactions. Eight-week-old miR-183/96/182 knockout (ko) mice and their wild-type littermates (wt) were used. The central cornea of anesthetized mice was scarred and infected with Pseudomonas aeruginosa (PA), strain 19660. Corneal disease was graded at 1, 3, and 5 days postinfection (dpi). Corneal RNA was harvested for quantitative RT-PCR. Polymorphonuclear neutrophils (PMN) were enumerated by myeloperoxidase assays; the number of viable bacteria was determined by plate counts, and ELISA assays were performed to determine cytokine protein levels. A macrophage (Mϕ) cell line and elicited peritoneal PMN were used for in vitro functional assays. MicroRNA-183/96/182 is expressed in the cornea, and in Mϕ and PMN of both mice and humans. Inactivation of miR-183/96/182 resulted in decreased corneal nerve density compared with wt mice. Overexpression of miR-183/96/182 in Mϕ decreased, whereas knockdown or inactivation of miR-183/96/182 in Mϕ and PMN increased their capacity for phagocytosis and intracellular killing of PA. In PA-infected corneas, ko mice showed decreased proinflammatory neuropeptides such as substance P and chemoattractant molecules, MIP-2, MCP1, and ICAM1; decreased number of PMN at 1 and 5 dpi; increased viable bacterial load at 1 dpi, but decreased at 5 dpi; and markedly decreased corneal disease. MicroRNA-183/96/182 modulates the corneal response to bacterial infection through its regulation of corneal innervation and innate immunity.

Traumatic corneal flap displacement after laser in situ keratomileusis (LASIK).

PubMed

Tsai, Tsung-Han; Peng, Kai-Ling; Lin, Chien-Jen

2017-01-01

Laser in situ keratomileusis (LASIK) is the most common and popular procedure performed for the correction of refractive errors in the last two decades. We report a case of traumatic flap displacement with flap folding which occurred 3 years after LASIK was performed. Previous literature suggests that vision prognosis would be closely related to proper and prompt management of traumatic flap displacement with flap folding 3 years after LASIK. A 23-year-old female presented to our hospital who had undergone uneventful LASIK in both eyes 3 years prior. Unfortunately, she had suffered a blunt trauma in her right eye in a car accident. A late onset of corneal flap displacement was found with upper and lower portion of the flap being folded inside the corneal bed. Surgical intervention for debridement with subsequent reposition of corneal flap was performed as soon as possible in the operating room. A bandage contact lens was placed, and topical antibiotic and corticosteroids were given postoperatively. Two days after the operation, the displaced corneal flap was found to be well attached smoothly on the corneal bed without folds. The best-corrected visual acuity was 6/6 with refraction of -0.75 D to 1.0 D ×175° in her right eye 1 month later. We reviewed a total of 19 published cases of late-onset traumatic flap dislocations or displacements after LASIK with complete data from 2000 to 2014. Traumatic displacement of corneal flaps after LASIK may occur after blunt injury with specific direction of force to the flap margin, especially tangential one. According to the previous literature, late-onset traumatic flap displacement may happen at any time after LASIK and be caused by various types of injuries. Fortunately, good visual function could mostly be restored with immediate and proper management.

Corneal Collagen Crosslinking Combined with Phototherapeutic Keratectomy and Photorefractive Keratectomy for Corneal Ectasia after Laser in situ Keratomileusis.

PubMed

Zhu, Wei; Han, Yunfei; Cui, Changxia; Xu, Wenwen; Wang, Xuan; Dou, Xiaoxiao; Xu, Linlin; Xu, Yanyun; Mu, Guoying

2018-01-01

The aim of this study was to analyze the effects of corneal crosslinking (CXL) combined with phototherapeutic keratectomy (PTK) and photorefractive keratectomy (PRK) in halting the progression and improving the visual function of corneal ectasia after laser in situ keratomileusis (LASIK). PTK-PRK-CXL was performed on 14 eyes of 14 patients who developed corneal ectasia after LASIK. The visual acuity, spherical refraction and cylinder, corneal topography indices, thinnest corneal thickness (TCT), and endothelial cell count were evaluated at baseline and at 1, 3, 6, and 12 months postoperatively. The mean uncorrected visual acuity improved significantly from 0.64 ± 0.36 logMAR preoperatively to 0.19 ± 0.12 logMAR at 12 months of follow-up (p < 0.001), while the mean best corrected visual acuity improved from 0.21 ± 0.14 logMAR at baseline to 0.04 ± 0.10 logMAR at 12 months postoperatively (p < 0.001). A significant decrease was observed in Kmax and Kmean values from 52.51 ± 6.74 and 43.55 ± 3.37 D at baseline to 45.72 ± 5.18 (p < 0.001) and 40.60 ± 3.05 D (p < 0.001) at the 1-year follow-up. The mean TCT decreased significantly from 419.07 ± 36.56 µm before treatment to 320.93 ± 39.78 µm at 12 months of follow-up (p < 0.001), and there was no significant endothelial cell loss (p > 0.05) beyond 6 months after treatment. PTK-PRK-CXL is a promising procedure to halt the progression of post-LASIK keratectasia with significant visual quality improvement. © 2018 S. Karger AG, Basel.

Risk Factors for Corneal Infiltrative Events during Continuous Wear of Silicone Hydrogel Contact Lenses

PubMed Central

Lass, Jonathan H.; Sethi, Ajay; Debanne, Sara; Benetz, Beth Ann; Albright, Matthew; Gillespie, Beth; Kuo, Jana; Jacobs, Michael R.; Rimm, Alfred

2010-01-01

Purpose. This study determined which microbiologic, clinical, demographic, and behavioral factors are associated with corneal infiltrative events (CIEs) during continuous wear of silicone hydrogel (SH) contact lenses. Methods. Subjects (n = 205) were fitted with lotrafilcon A lenses for continuous wear and observed for 1 year. The main exposures of interest were corneal staining and bacterial lens contamination. Kaplan-Meier (KM) plots were used to estimate the cumulative unadjusted probability of remaining CIE free, and Cox proportional hazards regression was used to model the hazard of having a CIE, as a function of key predictor variables. Results. The KM-unadjusted cumulative probability of remaining CIE free was 73.3%. Approximately 53% of subjects had repeated episodes of corneal staining (mild or greater), and 11.3% had repeated episodes of moderate or greater corneal staining. Corneal staining was not associated with the development of a CIE. The frequency of substantial bacterial bioburden on worn lenses at the time of a CIE was 64.7%, compared with only 12.2% during uncomplicated wear. The presence of substantial lens bacterial bioburden was associated with the development of a CIE (adjusted hazards ratio [HR], 8.66; 95% confidence interval [CI], 2.88–26.01). Smoking was also associated with a CIE (adjusted HR, 4.13; 95% CI, 1.27–13.45). Conclusions. Corneal staining is common during continuous wear of SH lenses, but it is not associated with the development of a CIE. Smoking and substantial lens bacterial bioburden pose prominent risks of a CIE. In this study, more than 70% of the total risk of CIE in those with substantial lens bioburden is attributable to this exposure. (ClinicalTrials.gov number, NCT00727402). PMID:20538985

Effect of Orbital Decompression on Corneal Topography in Patients with Thyroid Ophthalmopathy

PubMed Central

Kim, Su Ah; Jung, Su Kyung; Paik, Ji Sun; Yang, Suk-Woo

2015-01-01

Objective To evaluate changes in corneal astigmatism in patients undergoing orbital decompression surgery. Methods This retrospective, non randomized comparative study involved 42 eyes from 21 patients with thyroid ophthalmopathy who underwent orbital decompression surgery between September 2011 and September 2014. The 42 eyes were divided into three groups: control (9 eyes), two-wall decompression (25 eyes), and three-wall decompression (8 eyes). The control group was defined as the contralateral eyes of nine patients who underwent orbital decompression surgery in only one eye. Corneal topography (Orbscan II), Hertel exophthalmometry, and intraocular pressure were measured at 1 month before and 3 months after surgery. Corneal topographic parameters analyzed were total astigmatism (TA), steepest axis (SA), central corneal thickness (CCT), and anterior chamber depth (ACD). Results Exophthalmometry values and intraocular pressure decreased significantly after the decompression surgery. The change (absolute value (|x|) of the difference) in astigmatism at the 3 mm zone was significantly different between the decompression group and the controls (p = 0.025). There was also a significant change in the steepest axis at the 3 mm zone between the decompression group and the controls (p = 0.033). An analysis of relevant changes in astigmatism showed that there was a dominant tendency for incyclotorsion of the steepest axis in eyes that underwent decompression surgery. Using Astig PLOT, the mean surgically induced astigmatism (SIA) was 0.21±0.88 D with an axis of 46±22°, suggesting that decompression surgery did change the corneal shape and induced incyclotorsion of the steepest axis. Conclusions There was a significant change in corneal astigmatism after orbital decompression surgery and this change was sufficient to affect the optical function of the cornea. Surgeons and patients should be aware of these changes. PMID:26352432

Small fiber neuropathy in Parkinson's disease: A clinical, pathological and corneal confocal microscopy study.

PubMed

Kass-Iliyya, Lewis; Javed, Saad; Gosal, David; Kobylecki, Christopher; Marshall, Andrew; Petropoulos, Ioannis N; Ponirakis, Georgios; Tavakoli, Mitra; Ferdousi, Maryam; Chaudhuri, Kallol Ray; Jeziorska, Maria; Malik, Rayaz A; Silverdale, Monty A

2015-12-01

Autonomic and somatic denervation is well established in Parkinson's disease (PD). (1) To determine whether corneal confocal microscopy (CCM) can non-invasively demonstrate small nerve fiber damage in PD. (2) To identify relationships between corneal nerve parameters, intraepidermal nerve fiber density (IENFD) and clinical features of PD. Twenty-six PD patients and 26 controls underwent CCM of both eyes. 24/26 PD patients and 10/26 controls underwent skin biopsies from the dorsa of both feet. PD patients underwent assessment of parasympathetic function [deep breathing heart rate variability (DB-HRV)], autonomic symptoms [scale for outcomes in Parkinson's disease - autonomic symptoms (SCOPA-AUT)], motor symptoms [UPDRS-III "ON"] and cumulative Levodopa dose. PD patients had significantly reduced corneal nerve fiber density (CNFD) with increased corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) compared to controls. CNBD and CNFL but not CNFD correlated inversely with UPDRS-III and SCOPA-AUT. All CCM parameters correlated strongly with DB-HRV. There was no correlation between CCM parameters and disease duration, cumulative Levodopa dose or pain. IENFD was significantly reduced in PD compared to controls and correlated with CNFD and UPDRS-III. However, unlike CCM measures, IENFD correlated with disease duration and cumulative Levodopa dose but not with autonomic dysfunction. CCM identifies corneal nerve fiber pathology, which correlates with autonomic symptoms, parasympathetic deficits and motor scores in patients with PD. IENFD is also reduced and correlates with CNFD and motor symptoms but not parasympathetic deficits, indicating it detects different aspects of peripheral nerve pathology in PD. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Corneal biomechanical properties from two-dimensional corneal flap extensiometry: application to UV-riboflavin cross-linking.

PubMed

Kling, Sabine; Ginis, Harilaos; Marcos, Susana

2012-07-27

Corneal biomechanical properties are usually measured by strip extensiometry or inflation methods. We developed a two-dimensional (2D) flap extensiometry technique, combining the advantages of both methods, and applied it to measure the effect of UV-Riboflavin cross-linking (CXL). Corneal flaps (13 pig/8 rabbit) from the de-epithelialized anterior stroma (96 μm) were mounted on a custom chamber, consisting of a BK7 lens, a reflective retina, and two reservoirs (filled with Riboflavin and silicone oil). Stretching the corneal flap during five pressure increase/decrease cycles (0-30 mm Hg) changed the refractive power of the system, whose Zernike aberrations were monitored with a ray-tracing aberrometer. Porcine flaps were used to test the system. Rabbits were treated with CXL unilaterally in vivo following standard clinical procedures. Flaps were measured 1 month postoperatively. An analytical model allowed estimating Young's modulus from the change in surface (strain) and pressure (stress). Confocal microscopy examination was performed before, and at different times after CXL. Flap curvature changed with increased function of IOP in pig flaps (23.4 × 10⁻³ D/mm Hg). In rabbit flaps curvature changed significantly less in 1 month post CXL (P = 0.026) than in untreated corneas [17.0 vs. 6.36 millidiopter (mD)/mm Hg]. Young's modulus was 2.29 megapascals (MPa) in porcine corneas, 1.98 MPa in untreated rabbit corneas, and 4.83 MPa in 1 month post CXL rabbit corneas. At the same time, highly reflective structures were observed in the rabbit midstroma after treatment. 2D flap extensiometry allows estimating corneal elasticity in vitro. The measurements are spatially resolved in depth, minimize the effects of corneal hydration, and preserve the integrity of the cornea. The method proved the efficacy of CXL in increasing corneal rigidity after 1 month in rabbits.

Accuracy of Corneal Thickness by Swept-Source Optical Coherence Tomography and Scheimpflug Camera in Virgin and Treated Fuchs Endothelial Dystrophy.

PubMed

Arnalich-Montiel, Francisco; Ortiz-Toquero, Sara; Auladell, Clara; Couceiro, Ana

2018-06-01

To assess intraobserver repeatability, intersession reproducibility, and agreement of swept-source Fourier-domain optical coherence tomography (SS-OCT) and the Scheimpflug camera in measuring corneal thickness in virgin and grafted eyes with Fuchs endothelial corneal dystrophy (FECD). Thirty-six control eyes, 35 FECD eyes, 30 FECD with corneal edema eyes, 25 Descemet stripping automated endothelial keratoplasty (DSAEK) eyes, and 29 Descemet membrane endothelial keratoplasty (DMEK) eyes were included. The apical center, pupillary center, and thinnest corneal thickness were determined in 3 consecutive images and repeated 2 weeks later. Repeatability and reproducibility coefficients, intraclass correlation coefficients, and 95% limits of agreement (LOA) between measurements were calculated. Agreement between devices was assessed using Bland-Altman analysis. Corneal thickness measurements were highly reproducible and repeatable with both systems. SS-OCT showed better repeatability in all corneal locations in the normal, FECD, FECD with edema, DSAEK, and DMEK groups (coefficient of variation ≤0.60%, ≤0.36%, ≤0.43%, ≤1.09%, and ≤0.48%, respectively) than the Scheimpflug (coefficient of variation ≤1.15%, ≤0.92%, ≤1.10%, ≤1.25%, and ≤1.14%, respectively). Between-session 95% LOA for SS-OCT was less than 3% for all groups except for the FECD with edema group, being almost double using the Scheimpflug camera. Differences between instruments were statistically significant in all groups and locations (P < 0.01) except in the DSAEK group (P ≤ 0.51); however, SS-OCT underestimated all measurements. SS-OCT provides better reproducible and repeatable measurements of corneal thickness than those obtained with the Scheimpflug camera in patients with FECD or an endothelial transplant. Variations between examinations higher than the 95% LOA observed in our study should raise awareness of changes in the endothelial function.

Method for Expressing Clinical and Statistical Significance of Ocular and Corneal Wavefront Error Aberrations

PubMed Central

Smolek, Michael K.

2011-01-01

Purpose The significance of ocular or corneal aberrations may be subject to misinterpretation whenever eyes with different pupil sizes or the application of different Zernike expansion orders are compared. A method is shown that uses simple mathematical interpolation techniques based on normal data to rapidly determine the clinical significance of aberrations, without concern for pupil and expansion order. Methods Corneal topography (Tomey, Inc.; Nagoya, Japan) from 30 normal corneas was collected and the corneal wavefront error analyzed by Zernike polynomial decomposition into specific aberration types for pupil diameters of 3, 5, 7, and 10 mm and Zernike expansion orders of 6, 8, 10 and 12. Using this 4×4 matrix of pupil sizes and fitting orders, best-fitting 3-dimensional functions were determined for the mean and standard deviation of the RMS error for specific aberrations. The functions were encoded into software to determine the significance of data acquired from non-normal cases. Results The best-fitting functions for 6 types of aberrations were determined: defocus, astigmatism, prism, coma, spherical aberration, and all higher-order aberrations. A clinical screening method of color-coding the significance of aberrations in normal, postoperative LASIK, and keratoconus cases having different pupil sizes and different expansion orders is demonstrated. Conclusions A method to calibrate wavefront aberrometry devices by using a standard sample of normal cases was devised. This method could be potentially useful in clinical studies involving patients with uncontrolled pupil sizes or in studies that compare data from aberrometers that use different Zernike fitting-order algorithms. PMID:22157570

Applications of corneal topography and tomography: a review.

PubMed

Fan, Rachel; Chan, Tommy Cy; Prakash, Gaurav; Jhanji, Vishal

2018-03-01

Corneal imaging is essential for diagnosing and management of a wide variety of ocular diseases. Corneal topography is used to characterize the shape of the cornea, specifically, the anterior surface of the cornea. Most corneal topographical systems are based on Placido disc that analyse rings that are reflected off the corneal surface. The posterior corneal surface cannot be characterized using Placido disc technology. Imaging of the posterior corneal surface is useful for diagnosis of corneal ectasia. Unlike corneal topographers, tomographers generate a three-dimensional recreation of the anterior segment and provide information about the corneal thickness. Scheimpflug imaging is one of the most commonly used techniques for corneal tomography. The cross-sectional images generated by a rotating Scheimpflug camera are used to locate the anterior and posterior corneal surfaces. The clinical uses of corneal topography include, diagnosis of corneal ectasia, assessment of corneal astigmatism, and refractive surgery planning. This review will discuss the applications of corneal topography and tomography in clinical practice. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

CD147 Required for Corneal Endothelial Lactate Transport

PubMed Central

Li, Shimin; Nguyen, Tracy T.; Bonanno, Joseph A.

2014-01-01

Purpose. CD147/basigin is a chaperone for lactate:H+ cotransporters (monocarboxylate transporters) MCT1 and MCT4. We tested the hypothesis that MCT1 and -4 in corneal endothelium contribute to lactate efflux from stroma to anterior chamber and that silencing CD147 expression would cause corneal edema. Methods. CD147 was silenced via small interfering ribonucleic acid (siRNA) transfection of rabbit corneas ex vivo and anterior chamber lenti-small hairpin RNA (shRNA) pseudovirus in vivo. CD147 and MCT expression was examined by Western blot, RT-PCR, and immunofluorescence. Functional effects were examined by measuring lactate-induced cell acidification, corneal lactate efflux, [lactate], central cornea thickness (CCT), and Azopt (a carbonic anhydrase inhibitor) sensitivity. Results. In ex vivo corneas, 100 nM CD147 siRNA reduced CD147, MCT1, and MCT4 expression by 85%, 79%, and 73%, respectively, while MCT2 expression was unaffected. CD147 siRNA decreased lactate efflux from 3.9 ± 0.81 to 1.5 ± 0.37 nmol/min, increased corneal [lactate] from 19.28 ± 7.15 to 56.73 ± 8.97 nmol/mg, acidified endothelial cells (pHi = 6.83 ± 0.07 vs. 7.19 ± 0.09 in control), and slowed basolateral lactate-induced acidification from 0.0034 ± 0.0005 to 0.0012 ± 0.0005 pH/s, whereas apical acidification was unchanged. In vivo, CD147 shRNA increased CCT by 28.1 ± 0.9 μm at 28 days; Azopt increased CCT to 24.4 ± 3.12 vs. 12.0 ± 0.48 μm in control, and corneal [lactate] was 47.63 ± 6.29 nmol/mg in shCD147 corneas and 17.82 ± 4.93 nmol/mg in paired controls. Conclusions. CD147 is required for the expression of MCT1 and MCT4 in the corneal endothelium. Silencing CD147 slows lactate efflux, resulting in stromal lactate accumulation and corneal edema, consistent with lactate efflux as a significant component of the corneal endothelial pump. PMID:24970254

CD147 required for corneal endothelial lactate transport.

PubMed

Li, Shimin; Nguyen, Tracy T; Bonanno, Joseph A

2014-06-26

CD147/basigin is a chaperone for lactate:H(+) cotransporters (monocarboxylate transporters) MCT1 and MCT4. We tested the hypothesis that MCT1 and -4 in corneal endothelium contribute to lactate efflux from stroma to anterior chamber and that silencing CD147 expression would cause corneal edema. CD147 was silenced via small interfering ribonucleic acid (siRNA) transfection of rabbit corneas ex vivo and anterior chamber lenti-small hairpin RNA (shRNA) pseudovirus in vivo. CD147 and MCT expression was examined by Western blot, RT-PCR, and immunofluorescence. Functional effects were examined by measuring lactate-induced cell acidification, corneal lactate efflux, [lactate], central cornea thickness (CCT), and Azopt (a carbonic anhydrase inhibitor) sensitivity. In ex vivo corneas, 100 nM CD147 siRNA reduced CD147, MCT1, and MCT4 expression by 85%, 79%, and 73%, respectively, while MCT2 expression was unaffected. CD147 siRNA decreased lactate efflux from 3.9 ± 0.81 to 1.5 ± 0.37 nmol/min, increased corneal [lactate] from 19.28 ± 7.15 to 56.73 ± 8.97 nmol/mg, acidified endothelial cells (pHi = 6.83 ± 0.07 vs. 7.19 ± 0.09 in control), and slowed basolateral lactate-induced acidification from 0.0034 ± 0.0005 to 0.0012 ± 0.0005 pH/s, whereas apical acidification was unchanged. In vivo, CD147 shRNA increased CCT by 28.1 ± 0.9 μm at 28 days; Azopt increased CCT to 24.4 ± 3.12 vs. 12.0 ± 0.48 μm in control, and corneal [lactate] was 47.63 ± 6.29 nmol/mg in shCD147 corneas and 17.82 ± 4.93 nmol/mg in paired controls. CD147 is required for the expression of MCT1 and MCT4 in the corneal endothelium. Silencing CD147 slows lactate efflux, resulting in stromal lactate accumulation and corneal edema, consistent with lactate efflux as a significant component of the corneal endothelial pump. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

The Influence of Lamellar Orientation on Corneal Material Behavior: Biomechanical and Structural Changes in an Avian Corneal Disorder

PubMed Central

Elsheikh, Ahmed; Kassem, Wael; Kamma-Lorger, Christina S.; Hocking, Paul M.; White, Nick; Inglehearn, Chris F.; Ali, Manir; Meek, Keith M.

2011-01-01

Purpose. Retinopathy, globe enlarged (RGE) is an inherited genetic disease of chickens with a corneal phenotype characterized by loss of tissue curvature and changes in peripheral collagen fibril alignment. This study aimed to characterize the material behavior of normal and RGE chicken corneas under inflation and compare this with new spatial- and depth-resolved microstructural information to investigate how stromal fibril architecture determines corneal behavior under intraocular pressure (IOP). Methods. Six RGE chicken corneas and six age-matched normal controls were tested using trephinate inflation and their stress-strain behavior determined as a function of posterior pressure. Second harmonic generation mulitphoton microscopy was used to compare the in-plane appearance and degree of through-plane interlacing of collagen lamellae between normal and mutant corneas. Results. RGE corneas displayed a 30–130% increase in material stiffness [Etangent(RGE) = 0.94 ± 0.18 MPa to 3.09 ± 0.66 MPa; Etangent(normals) = 0.72 ± 0.13 MPa to 1.34 ± 0.35 MPa] (P ≤ 0.05). The normal in-plane disposition of anterior collagen in the peripheral cornea was altered in RGE but through-plane lamellar interlacing was unaffected. Conclusions. This article demonstrates changes in corneal material behavior in RGE that are qualitatively consistent with microstructural collagen alterations identified both herein and previously. This study indicates that, in general, changes in stromal fibril orientation may significantly affect corneal material behavior and thereby its response to IOP. PMID:21051696

Slit-lamp photography and videography with high magnifications

PubMed Central

Yuan, Jin; Jiang, Hong; Mao, Xinjie; Ke, Bilian; Yan, Wentao; Liu, Che; Cintrón-Colón, Hector R; Perez, Victor L; Wang, Jianhua

2015-01-01

Purpose To demonstrate the use of the slit-lamp photography and videography with extremely high magnifications for visualizing structures of the anterior segment of the eye. Methods A Canon 60D digital camera with Movie Crop Function was adapted into a Nikon FS-2 slit-lamp to capture still images and video clips of the structures of the anterior segment of the eye. Images obtained using the slit-lamp were tested for spatial resolution. The cornea of human eyes was imaged with the slit-lamp and the structures were compared with the pictures captured using the ultra-high resolution optical coherence tomography (UHR-OCT). The central thickness of the corneal epithelium and total cornea was obtained using the slit-lamp and the results were compared with the thickness obtained using UHR-OCT. Results High-quality ocular images and higher spatial resolutions were obtained by using the slit-lamp with extremely high magnifications and Movie Crop Function, rather than the traditional slit-lamp. The structures and characteristics of the cornea, such as the normal epithelium, abnormal epithelium of corneal intraepithelial neoplasia, LASIK interface, and contact lenses, were clearly visualized using this device. These features were confirmed by comparing the obtained images with those acquired using UHR-OCT. Moreover, the tear film debris on the ocular surface and the corneal nerve in the anterior corneal stroma were also visualized. The thicknesses of the corneal epithelium and total cornea were similar to that measured using UHR-OCT (P < 0.05). Conclusions We demonstrated that the slit-lamp photography and videography with extremely high magnifications allows better visualization of the anterior segment structures of the eye, especially of the epithelium, when compared with the traditional slit-lamp. PMID:26020484

An RNAi Screen for Genes Involved in Nanoscale Protrusion Formation on Corneal Lens in Drosophila melanogaster.

PubMed

Minami, Ryunosuke; Sato, Chiaki; Yamahama, Yumi; Kubo, Hideo; Hariyama, Takahiko; Kimura, Ken-Ichi

2016-12-01

The "moth-eye" structure, which is observed on the surface of corneal lens in several insects, supports anti-reflective and self-cleaning functions due to nanoscale protrusions known as corneal nipples. Although the morphology and function of the "moth-eye" structure, are relatively well studied, the mechanism of protrusion formation from cell-secreted substances is unknown. In Drosophila melanogaster, a compound eye consists of approximately 800 facets, the surface of which is formed by the corneal lens with nanoscale protrusions. In the present study, we sought to identify genes involved in "moth-eye" structure, formation in order to elucidate the developmental mechanism of the protrusions in Drosophila. We re-examined the aberrant patterns in classical glossy-eye mutants by scanning electron microscope and classified the aberrant patterns into groups. Next, we screened genes encoding putative structural cuticular proteins and genes involved in cuticular formation using eye specific RNAi silencing methods combined with the Gal4/UAS expression system. We identified 12 of 100 candidate genes, such as cuticular proteins family genes (Cuticular protein 23B and Cuticular protein 49Ah), cuticle secretion-related genes (Syntaxin 1A and Sec61 ββ subunit), ecdysone signaling and biosynthesis-related genes (Ecdysone receptor, Blimp-1, and shroud), and genes involved in cell polarity/cell architecture (Actin 5C, shotgun, armadillo, discs large1, and coracle). Although some of the genes we identified may affect corneal protrusion formation indirectly through general patterning defects in eye formation, these initial findings have encouraged us to more systematically explore the precise mechanisms underlying the formation of nanoscale protrusions in Drosophila.

3D Functional Corneal Stromal Tissue Equivalent Based on Corneal Stromal Stem Cells and Multi-Layered Silk Film Architecture.

PubMed

Ghezzi, Chiara E; Marelli, Benedetto; Omenetto, Fiorenzo G; Funderburgh, James L; Kaplan, David L

2017-01-01

The worldwide need for human cornea equivalents continues to grow. Few clinical options are limited to allogenic and synthetic material replacements. We hypothesized that tissue engineered human cornea systems based on mechanically robust, patterned, porous, thin, optically clear silk protein films, in combination with human corneal stromal stem cells (hCSSCs), would generate 3D functional corneal stroma tissue equivalents, in comparison to previously developed 2D approaches. Silk film contact guidance was used to control the alignment and distribution of hCSSCs on RGD-treated single porous silk films, which were then stacked in an orthogonally, multi-layered architecture and cultured for 9 weeks. These systems were compared similar systems generated with human corneal fibroblasts (hCFs). Both cell types were viable and preferentially aligned along the biomaterial patterns for up to 9 weeks in culture. H&E histological sections showed that the systems seeded with the hCSSCs displayed ECM production throughout the entire thickness of the constructs. In addition, the ECM proteins tested positive for keratocyte-specific tissue markers, including keratan sulfate, lumican, and keratocan. The quantification of hCSSC gene expression of keratocyte-tissue markers, including keratocan, lumican, human aldehyde dehydrogenase 3A1 (ALDH3A1), prostaglandin D2 synthase (PTDGS), and pyruvate dehydrogenase kinase, isozyme 4 (PDK4), within the 3D tissue systems demonstrated upregulation when compared to 2D single silk films and to the systems generated with the hCFs. Furthermore, the production of ECM from the hCSSC seeded systems and subsequent remodeling of the initial matrix significantly improved cohesiveness and mechanical performance of the constructs, while maintaining transparency after 9 weeks.

A new fish scale-derived scaffold for corneal regeneration.

PubMed

Lin, Chien Chen; Ritch, Robert; Lin, Shang Ming; Ni, Mei-Hui; Chang, Yu-Chung; Lu, Yi Lung; Lai, Hong Ji; Lin, Feng-Huei

2010-02-26

The purpose of this study is to develop a novel scaffold, derived from fish scales, as an alternative functional material with sufficient mechanical strength for corneal regenerative applications. Fish scales, which are usually considered as marine wastes, were acellularized, decalcified and fabricated into collagen scaffolds. The microstructure of the acellularized scaffold was imaged by scanning electron microscopy (SEM). The acellularization and decalcification treatments did not affect the naturally 3-dimentional, highly centrally-oriented micropatterned structure of the material. To assess the cytocompatibility of the scaffold with corneal cells, rabbit corneal cells were cultured on the scaffold and examined under SEM and confocal microscopy at different time periods. Rapid cell proliferation and migration on the scaffold were observed under SEM and confocal microscopy. The highly centrally-oriented micropatterned structure of the scaffold was beneficial for efficient nutrient and oxygen supply to the cells cultured in the three-dimensional matrices, and therefore it is useful for high-density cell seeding and spreading. Collectively, we demonstrate the superior cellular conductivity of the newly developed material. We provide evidences for the feasibility of the scaffold as a template for corneal cells growth and migration, and thus the fish scale-derived scaffold can be developed as a promising material for tissue-engineering of cornea.

Removal of the basement membrane enhances corneal wound healing.

PubMed

Pal-Ghosh, Sonali; Pajoohesh-Ganji, Ahdeah; Tadvalkar, Gauri; Stepp, Mary Ann

2011-12-01

Recurrent corneal erosions are painful and put patients' vision at risk. Treatment typically begins with debridement of the area around the erosion site followed by more aggressive treatments. An in vivo mouse model has been developed that reproducibly induces recurrent epithelial erosions in wild-type mice spontaneously within two weeks after a single 1.5 mm corneal debridement wound created using a dulled-blade. This study was conducted to determine whether 1) inhibiting MMP9 function during healing after dulled-blade wounding impacts erosion development and 2) wounds made with a rotating-burr heal without erosions. Oral or topical inhibition of MMPs after dulled-blade wounding does not improve healing. Wounds made by rotating-burr heal with significantly fewer erosions than dulled-blade wounds. The localization of MMP9, β4 integrin and basement membrane proteins (LN332 and type VII collagen), immune cell influx, and reinnervation of the corneal nerves were compared after both wound types. Rotating-burr wounds remove the anterior basement membrane centrally but not at the periphery near the wound margin, induce more apoptosis of corneal stromal cells, and damage more stromal nerve fibers. Despite the fact that rotating-burr wounds do more damage to the cornea, fewer immune cells are recruited and significantly more wounds resolve completely. Copyright © 2011 Elsevier Ltd. All rights reserved.

Complete Metabolome and Lipidome Analysis Reveals Novel Biomarkers in the Human Diabetic Corneal Stroma

PubMed Central

Priyadarsini, Shrestha; McKay, Tina B; Sarker-Nag, Akhee; Allegood, Jeremy; Chalfant, Charles; Ma, Jian-Xing; Karamichos, Dimitrios

2016-01-01

Prolonged hyperglycemia during diabetes mellitus can cause severe ophthalmic complications affecting both the anterior and posterior ocular segments leading to impaired vision or blindness. Diabetes-induced corneal pathologies are associated with decreased wound healing capacity, corneal edema, and altered epithelial basement membrane. The mechanism by which diabetes modulates structure and function within the corneal stroma are unknown. In our study, we characterized the effects of diabetes on extracellular matrix, lipid transport, and cellular metabolism by defining the entire metabolome and lipidome of Type 1 and Type 2 human diabetic corneal stroma. Significant increases in Collagen I and III were found in diabetic corneas suggesting that diabetes promotes defects in matrix structure leading to scarring. Furthermore, increased lipid content, including sphingosine-1-phosphate and dihydrosphingosine, in diabetic corneas compared to healthy controls were measured suggesting altered lipid retention. Metabolomics analysis identified elevated tryptophan metabolites, independent of glucose metabolism, which correlated with upregulation of the Kynurenine pathway in diabetic corneas. We also found significant upregulation of novel biomarkers aminoadipic acid, D,L-pipecolic acid, and dihydroorotate. Our study links aberrant tryptophan metabolism to end-stage pathologies associated with diabetes indicating the potential of the Kynurenine pathway as a therapeutic target for inhibiting diabetes-associated defects in the eye. PMID:27742548

Corneal Confocal Microscopy Detects Corneal Nerve Damage in Patients Admitted With Acute Ischemic Stroke.

PubMed

Khan, Adnan; Akhtar, Naveed; Kamran, Saadat; Ponirakis, Georgios; Petropoulos, Ioannis N; Tunio, Nahel A; Dargham, Soha R; Imam, Yahia; Sartaj, Faheem; Parray, Aijaz; Bourke, Paula; Khan, Rabia; Santos, Mark; Joseph, Sujatha; Shuaib, Ashfaq; Malik, Rayaz A

2017-11-01

Corneal confocal microscopy can identify corneal nerve damage in patients with peripheral and central neurodegeneration. However, the use of corneal confocal microscopy in patients presenting with acute ischemic stroke is unknown. One hundred thirty patients (57 without diabetes mellitus [normal glucose tolerance], 32 with impaired glucose tolerance, and 41 with type 2 diabetes mellitus) admitted with acute ischemic stroke, and 28 age-matched healthy control participants underwent corneal confocal microscopy to quantify corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length. There was a significant reduction in corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length in stroke patients with normal glucose tolerance ( P <0.001, P <0.001, P <0.001), impaired glucose tolerance ( P =0.004, P <0.001, P =0.002), and type 2 diabetes mellitus ( P <0.001, P <0.001, P <0.001) compared with controls. HbA1c and triglycerides correlated with corneal nerve fiber density ( r =-0.187, P =0.03; r =-0.229 P =0.01), corneal nerve fiber length ( r =-0.228, P =0.009; r =-0.285; P =0.001), and corneal nerve branch density ( r =-0.187, P =0.033; r =-0.229, P =0.01). Multiple linear regression showed no independent associations between corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length and relevant risk factors for stroke. Corneal confocal microscopy is a rapid noninvasive ophthalmic imaging technique that identifies corneal nerve fiber loss in patients with acute ischemic stroke. © 2017 American Heart Association, Inc.

Corneal Curvature, Astigmatism, and Aberrations in Marfan Syndrome with Lens Subluxation: Evaluation by Pentacam HR System.

PubMed

Chen, Jiahui; Jing, Qinghe; Tang, Yating; Qian, Dongjin; Lu, Yi; Jiang, Yongxiang

2018-03-06

Marfan syndrome (MFS) is associated with abnormalities of corneal biometric characteristics. We conducted a retrospective case-control study including 55 eyes of the MFS patients with lens subluxation and 53 normal eyes of the control subjects to evaluate the corneal curvature, astigmatism and aberrations using a rotating Scheimpflug camera (Pentacam HR). Compared with the control group, the anterior, posterior, and total corneal curvature were flatter in the MFS group. The anterior and total corneal astigmatism were higher in the MFS patients, whereas the posterior corneal astigmatism was not significantly different between the two groups. Regarding the total corneal aberrations, the root mean square (RMS) aberrations, RMS higher-order aberrations and RMS lower-order aberrations increased, whereas the spherical aberration decreased in the MFS patients. Corneal parameters had potential diagnostic values for MFS patients with lens subluxation and the more reasonable cutoffs were the values of corneal curvature <41.35 D, corneal astigmatism >0.85 D and spherical aberration <0.188 μm. Corneal biometric characteristics of MFS patients with lens subluxation include decreased corneal curvature, higher corneal astigmatism, larger corneal aberrations, and lower spherical aberration. Corneal curvature, corneal astigmatism, and spherical aberration are better diagnostic tools for suspicious MFS.

Structure and Biological Roles of Mucin-type O-glycans at the Ocular Surface

PubMed Central

Guzman-Aranguez, Ana; Argüeso, Pablo

2010-01-01

Mucins are major components in mucus secretions and apical cell membranes on wet-surfaced epithelia. Structurally, they are characterized by the presence of tandem repeat domains containing heavily O-glycosylated serine and threonine residues. O-glycans contribute to maintaining the highly extended and rigid structure of mucins, conferring to them specific physical and biological properties essential for their protective functions. At the ocular surface epithelia, mucin-type O-glycan chains are short and predominantly sialylated, perhaps reflecting specific requirements of the ocular surface. Traditionally, secreted mucins and their O-glycans in the tear film have been involved in the clearance of debris and pathogens from the surface of the eye. New evidence, however, shows that O-glycans on the cell-surface glycocalyx have additional biological roles in the protection of corneal and conjunctival epithelia, such as preventing bacterial adhesion, promoting boundary lubrication, and maintaining the epithelial barrier function through their interaction with galectin-3. Abnormalities in mucin-type O-glycosylation have been identified in many disorders where the stability of the ocular surface is compromised. This review summarizes recent advances in understanding the structure, biosynthesis, and function of mucin-type O-glycans at the ocular surface and their alteration in ocular surface disease. PMID:20105403

[Corneal transparency: anatomical basis and evaluation methods].

PubMed

Avetisov, S E; Narbut, M N

Being just a relatively small part of the fibrous tunic of the eyeball, the cornea is, nevertheless, unique in terms of the variety of its functions. Because the cornea differs significantly from other protective frames in its structure, it provides the possibility of light transmission and strong refraction that largely contributes to the total refraction of the eye. The development of ophthalmology is impossible without improving methods of adequate anatomical and functional assessment of the eye not only as a whole, but also as a collection of interacting structures.In this regard, examination methods of the cornea have undergone significant advances in recent years. So far, the level of corneal transparency has been judged by biomicroscopy findings or indirect characteristics (thickness, structure, etc.). Confocal microscopy of the cornea and wave-based examinations involving one of the available laser interferometers (OCT or HRT) are also used. However, the data obtained with these methods resembles that of layer-specific reflectometry, i.e. the magnitude of directed reflection of the light beam from corneal corpuscles, which does not completely agree with the classical idea of transparency.

Association between culture results of corneal scrapings and culture and histopathology results of corneal tissues in therapeutic keratoplasty.

PubMed

Das, Sujata; Sharma, Savitri; Priyadarshini, Omega; Sahu, Srikant K; Kar, Sarita; Vemuganti, Geeta K

2011-09-01

To correlate the culture results of corneal scrapings with culture and histopathology results of corneal tissues in therapeutic keratoplasty. A retrospective analysis of the culture results of corneal scrapings and corneal tissues of eyes that received therapeutic penetrating keratoplasty at a tertiary eye care center between December 2006 and November 2008 was conducted. As per the preferred practice, those cases that did not respond to appropriate antimicrobial therapy and/or presented with a large infiltrate/perforation received therapeutic keratoplasty. The microbiology and histopathology findings of the corneal tissues were compared. Thirty-eight therapeutic keratoplasties were performed on 36 patients. Although all cases had histopathology and culture of the corneal tissue, corneal scrapings were not performed in 4 cases. Corneal scrapings and corneal tissues were culture-positive in 76% (26 of 34) and 60% (23 of 38) of cases, respectively. In 8 cases, the corneal scrapings and corneal tissues yielded identical organisms, whereas different organisms grew in 4 cases. In 6 cases, the corneal tissues were culture-positive but the corneal scrapings were sterile. In 20 cases, the corneal tissues were culture-positive for fungus and also showed fungal filaments in their corresponding histopathology specimens. Corneal tissue culture can provide additional information in cases undergoing therapeutic keratoplasty. It helps to determine the management of patients after keratoplasty.

Glutaminolysis is Essential for Energy Production and Ion Transport in Human Corneal Endothelium.

PubMed

Zhang, Wenlin; Li, Hongde; Ogando, Diego G; Li, Shimin; Feng, Matthew; Price, Francis W; Tennessen, Jason M; Bonanno, Joseph A

2017-02-01

Corneal endothelium (CE) is among the most metabolically active tissues in the body. This elevated metabolic rate helps the CE maintain corneal transparency by its ion and fluid transport properties, which when disrupted, leads to visual impairment. Here we demonstrate that glutamine catabolism (glutaminolysis) through TCA cycle generates a large fraction of the ATP needed to maintain CE function, and this glutaminolysis is severely disrupted in cells deficient in NH 3 :H + cotransporter Solute Carrier Family 4 Member 11 (SLC4A11). Considering SLC4A11 mutations leads to corneal endothelial dystrophy and sensorineural deafness, our results indicate that SLC4A11-associated developmental and degenerative disorders result from altered glutamine catabolism. Overall, our results describe an important metabolic mechanism that provides CE cells with the energy required to maintain high level transport activity, reveal a direct link between glutamine metabolism and developmental and degenerative neuronal diseases, and suggest an approach for protecting the CE during ophthalmic surgeries. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Modeling the influence of LASIK surgery on optical properties of the human eye

NASA Astrophysics Data System (ADS)

Szul-Pietrzak, Elżbieta; Hachoł, Andrzej; Cieślak, Krzysztof; Drożdż, Ryszard; Podbielska, Halina

2011-11-01

The aim was to model the influence of LASIK surgery on the optical parameters of the human eye and to ascertain which factors besides the central corneal radius of curvature and central thickness play the major role in postsurgical refractive change. Ten patients were included in the study. Pre- and postsurgical measurements included standard refraction, anterior corneal curvature and pachymetry. The optical model used in the analysis was based on the Le Grand and El Hage schematic eye, modified by the measured individual parameters of corneal geometry. A substantial difference between eye refractive error measured after LASIK and estimated from the eye model was observed. In three patients, full correction of the refractive error was achieved. However, analysis of the visual quality in terms of spot diagrams and optical transfer functions of the eye optical system revealed some differences in these measurements. This suggests that other factors besides corneal geometry may play a major role in postsurgical refraction. In this paper we investigated whether the biomechanical properties of the eyeball and changes in intraocular pressure could account for the observed discrepancies.

LASIK and dry eye.

PubMed

Toda, Ikuko

2007-01-01

Dry eye is one of the most common complications after laser-assisted in situ keratomileusis (LASIK). The clinical signs of post-LASIK dry eye include positive vital staining of ocular surface, decreased tear film breakup time and Schirmer test, reduced corneal sensitivity, and decreased functional visual acuity. The symptoms and signs last at least 1 month after LASIK. Although the mechanisms for developing post-LASIK dry eye are not completely understood, loss of corneal innervation by flap-making may affect the reflex loops of the corneal-lacrimal gland, corneal-blinking, and blinking-meibomian gland, and blinking-meibomian gland, resulting in decreased aqueous and lipid tear secretion and mucin expression. As LASIK enhancement by flap-lifting induces less dry eye symptoms and signs than first surgery, it is suggested that other factors rather than loss of neurotrophic effect may be involved in the mechanisms of post-LASIK dry eye. The treatments of dry eye include artificial tears, topical cyclosporine, hot compress, punctal plugs, and autologous serum eye drops. For patients with severe preoperative dry eye, a combination of punctal plugs and serum eye drops is required to be used before surgery.

Hyperspectral Image Enhancement and Mixture Deep-Learning Classification of Corneal Epithelium Injuries.

PubMed

Noor, Siti Salwa Md; Michael, Kaleena; Marshall, Stephen; Ren, Jinchang

2017-11-16

In our preliminary study, the reflectance signatures obtained from hyperspectral imaging (HSI) of normal and abnormal corneal epithelium tissues of porcine show similar morphology with subtle differences. Here we present image enhancement algorithms that can be used to improve the interpretability of data into clinically relevant information to facilitate diagnostics. A total of 25 corneal epithelium images without the application of eye staining were used. Three image feature extraction approaches were applied for image classification: (i) image feature classification from histogram using a support vector machine with a Gaussian radial basis function (SVM-GRBF); (ii) physical image feature classification using deep-learning Convolutional Neural Networks (CNNs) only; and (iii) the combined classification of CNNs and SVM-Linear. The performance results indicate that our chosen image features from the histogram and length-scale parameter were able to classify with up to 100% accuracy; particularly, at CNNs and CNNs-SVM, by employing 80% of the data sample for training and 20% for testing. Thus, in the assessment of corneal epithelium injuries, HSI has high potential as a method that could surpass current technologies regarding speed, objectivity, and reliability.

Wavelet Representation of the Corneal Pulse for Detecting Ocular Dicrotism

PubMed Central

Melcer, Tomasz; Danielewska, Monika E.; Iskander, D. Robert

2015-01-01

Purpose To develop a reliable and powerful method for detecting the ocular dicrotism from non-invasively acquired signals of corneal pulse without the knowledge of the underlying cardiopulmonary information present in signals of ocular blood pulse and the electrical heart activity. Methods Retrospective data from a study on glaucomatous and age-related changes in corneal pulsation [PLOS ONE 9(7),(2014):e102814] involving 261 subjects was used. Continuous wavelet representation of the signal derivative of the corneal pulse was considered with a complex Gaussian derivative function chosen as mother wavelet. Gray-level Co-occurrence Matrix has been applied to the image (heat-maps) of CWT to yield a set of parameters that can be used to devise the ocular dicrotic pulse detection schemes based on the Conditional Inference Tree and the Random Forest models. The detection scheme was first tested on synthetic signals resembling those of a dicrotic and a non-dicrotic ocular pulse before being used on all 261 real recordings. Results A detection scheme based on a single feature of the Continuous Wavelet Transform of the corneal pulse signal resulted in a low detection rate. Conglomeration of a set of features based on measures of texture (homogeneity, correlation, energy, and contrast) resulted in a high detection rate reaching 93%. Conclusion It is possible to reliably detect a dicrotic ocular pulse from the signals of corneal pulsation without the need of acquiring additional signals related to heart activity, which was the previous state-of-the-art. The proposed scheme can be applied to other non-stationary biomedical signals related to ocular dynamics. PMID:25906236

Effect of biaxial versus coaxial microincision cataract surgery on optical quality of the cornea.

PubMed

Eliwa, Tamer Fahmy; Elsamkary, Mahmoud A; Hamza, Ismail

2015-06-01

Visual function is determined by a combination of the cornea, which has a larger effect and internal aberrations generated by the intraocular lens and those induced by the surgery. These corneal refractive changes are related to the location and size of the corneal incision. The smaller the incision, the lower the aberrations and the better the optical quality. To compare the effect of uneventful coaxial versus biaxial microincision cataract surgery (MICS) on the corneal aberrations. Retrospective interventional nonrandomized comparative case study comprised 40 eyes of 36 patients with primary senile cataract. They were divided into two groups: Group I (20 eyes) had operated by biaxial MICS and Group II (20 eyes) had operated by coaxial MICS. Each group were assessed by corneal topography and wavefront analysis over 6 mm pupil size preoperatively and 1-month postoperatively. Statistical analysis was performed using SPSS for Windows (version 17.0.1, SPSS, Inc.). The paired t-test was used to compare the mean values of corneal aberrations preoperatively and 1-month postoperatively in each group. There was a significant increase in trefoil and quatrefoil in biaxial MICS (P = 0.063, 0.032 respectively) while other aberrations insignificantly changed. The coaxial MICS showed a significant increase in root mean square (RMS) of total high order aberrations (HOAs) (P = 0.02) and coma (0.028), but not the others. In comparison to each other, there was the insignificant difference as regards astigmatism, RMS of individual and total HOAs. Coaxial and biaxial MICS are neutral on corneal astigmatism and aberrations.

Sequence, molecular properties, and chromosomal mapping of mouse lumican

NASA Technical Reports Server (NTRS)

Funderburgh, J. L.; Funderburgh, M. L.; Hevelone, N. D.; Stech, M. E.; Justice, M. J.; Liu, C. Y.; Kao, W. W.; Conrad, G. W.; Spooner, B. S. (Principal Investigator)

1995-01-01

PURPOSE. Lumican is a major proteoglycan of vertebrate cornea. This study characterizes mouse lumican, its molecular form, cDNA sequence, and chromosomal localization. METHODS. Lumican sequence was determined from cDNA clones selected from a mouse corneal cDNA expression library using a bovine lumican cDNA probe. Tissue expression and size of lumican mRNA were determined using Northern hybridization. Glycosidase digestion followed by Western blot analysis provided characterization of molecular properties of purified mouse corneal lumican. Chromosomal mapping of the lumican gene (Lcn) used Southern hybridization of a panel of genomic DNAs from an interspecific murine backcross. RESULTS. Mouse lumican is a 338-amino acid protein with high-sequence identity to bovine and chicken lumican proteins. The N-terminus of the lumican protein contains consensus sequences for tyrosine sulfation. A 1.9-kb lumican mRNA is present in cornea and several other tissues. Antibody against bovine lumican reacted with recombinant mouse lumican expressed in Escherichia coli and also detected high molecular weight proteoglycans in extracts of mouse cornea. Keratanase digestion of corneal proteoglycans released lumican protein, demonstrating the presence of sulfated keratan sulfate chains on mouse corneal lumican in vivo. The lumican gene (Lcn) was mapped to the distal region of mouse chromosome 10. The Lcn map site is in the region of a previously identified developmental mutant, eye blebs, affecting corneal morphology. CONCLUSIONS. This study demonstrates sulfated keratan sulfate proteoglycan in mouse cornea and describes the tools (antibodies and cDNA) necessary to investigate the functional role of this important corneal molecule using naturally occurring and induced mutants of the murine lumican gene.

The Relation of Ocular Surface Irregularity and Visual Disturbance in Early Stage Acanthamoeba Keratitis.

PubMed

Matsumoto, Yukihiro; Kodama, Asako; Goto, Eiki; Kawakita, Tetsuya; Dogru, Murat; Tsubota, Kazuo

2017-01-01

To evaluate the relation between ocular surface irregularity and visual disturbance in early stage Acanthamoeba keratitis (AK). Fifteen patients with culture-proven AK underwent routine ophthalmic examinations, including best-corrected visual acuity (BCVA) measurement, slitlamp biomicroscope examination, and corneal fluorescein dye staining test, in both the eyes. We also evaluated the corneal sensitivity with Cochet-Bonnet esthesiometer, tear functions by Schirmer's test, and ocular surface irregularity by corneal topography and compared the results with the contralateral healthy eyes in this study. The mean logarithm of the minimum angle of resolution BCVA (0.71±0.77) was significantly lower in the eyes with AK (P=0.002). Epithelial disorders were present in all eyes, and radial keratoneuritis in 14 eyes (93.3%). The mean corneal sensitivity (39.3±24.1 mm) was significantly lower in eyes with AK compared with the healthy eyes (P=0.005). The mean Schirmer's test value (22.5±12.0 mm) in eyes with AK was significantly higher compared with the healthy eyes (P=0.01). The ocular surface irregularity indices (the surface regularity index, 2.47±0.42; the surface asymmetry index, 3.24±1.31) were significantly higher in eyes with AK compared with contralateral healthy eyes (P<0.0001 and P<0.0001, respectively). The ocular surface disease in AK is associated with decrease in corneal sensitivity and increase in Schirmer's test value and ocular surface irregularity indices. The visual disturbance in AK may owe not only to corneal haze but also to ocular surface irregularity.

Biopharmaceutical evaluation of surface active ophthalmic excipients using in vitro and ex vivo corneal models.

PubMed

Juretić, Marina; Cetina-Čižmek, Biserka; Filipović-Grčić, Jelena; Hafner, Anita; Lovrić, Jasmina; Pepić, Ivan

2018-07-30

The objective of this study was to systematically investigate the effects of surface active ophthalmic excipients on the corneal permeation of ophthalmic drugs using in vitro (HCE-T cell-based model) and ex vivo (freshly excised porcine cornea) models. The permeation of four ophthalmic drugs (i.e., timolol maleate, chloramphenicol, diclofenac sodium and dexamethasone) across in vitro and ex vivo corneal models was evaluated in the absence and presence of four commonly used surface active ophthalmic excipients (i.e., Polysorbate 80, Tyloxapol, Cremophor® EL and Pluronic® F68). The concentration and self-aggregation-dependent effects of surface active ophthalmic excipients on ophthalmic drug permeability were studied from the concentration region where only dissolved monomer molecules of surface active ophthalmic excipients exist, as well as the concentration region in which aggregates of variable size and dispersion are spontaneously formed. Neither the surface active ophthalmic excipients nor the ophthalmic drugs at all concentrations that were tested significantly affected the barrier properties of both corneal models, as assessed by transepithelial electrical resistance (TEER) monitoring during the permeability experiments. The lowest concentration of all investigated surface active ophthalmic excipients did not significantly affect the ophthalmic drug permeability across both of the corneal models that were used. For three ophthalmic drugs (i.e., chloramphenicol, diclofenac sodium and dexamethasone), depressed in vitro and ex vivo permeability were observed in the concentration range of either Polysorbate 80, Tyloxapol, Cremophor® EL or Pluronic® F68, at which self-aggregation is detected. The effect was the most pronounced for Cremophor® EL (1 and 2%, w/V) and was the least pronounced for Pluronic® F68 (1%, w/V). However, all surface active ophthalmic excipients over the entire concentration range that was tested did not significantly affect the in vitro and ex vivo permeability of timolol maleate, which is the most hydrophilic ophthalmic drug that was investigated. The results of the dynamic light scattering measurements point to the association of ophthalmic drugs with self-aggregates of surface active ophthalmic excipients as the potential mechanism of the observed permeability-depressing effect of surface active ophthalmic excipients. A strong and statistically significant correlation was observed between in vitro and ex vivo permeability of ophthalmic drugs in the presence of surface active ophthalmic excipients, which indicates that the observed permeability-altering effects of surface active ophthalmic excipients were comparable and were mediated by the same mechanism in both corneal models. Copyright © 2018 Elsevier B.V. All rights reserved.

Evaluation of the Tear Function Tests and the Ocular Surface in First-Time Users of Silicone Hydrogel Contact Lenses.

PubMed

Yildiz Tasci, Yelda; Gürdal, Canan; Sarac, Ozge; Onusever, Aykut

2017-07-01

To evaluate the effects of three different silicone hydrogel contact lenses (SHCL), (balafilcon A, senofilcon A, and comfilcon A) on tear function tests, corneal thickness, and ocular surface cytology in first time contact lens users. In this prospective study, 120 eyes of 60 subjects were evaluated. Balafilcon A users were designated as group 1, senofilcon A users as group 2, and comfilcon A users as group 3. In all cases, before and after 6 months of contact lens wear, ocular surface disease index score (OSDI), tear breakup time (TBUT), Schirmer 1 test, central corneal thickness (CCT), central corneal epithelium thickness (CCET), and conjunctival impression cytology samples were evaluated. In group 1, 40 eyes of the 20 patients, in group 2, 40 eyes of the 20 patients, and in group 3, 40 eyes of the 20 patients were evaluated. The mean OSDI scores did not differ between the three groups after contact lens wear (p > 0.05). In group 1 and group 2, significant decrease was found in the mean TBUT 6 months after contact lens wear (p = 0.04, p < 0.001, respectively). In group 3, after 6 months of contact lens wear, the mean Schirmer 1 tear test was decreased significantly (p = 0.021). In all 3 groups, no significant change was observed in the mean CCT and CCET after contact lens wear (p > 0.05). After 6 months, the morphological changes in temporal and superior conjunctival epithelial cells were found to be significant in all groups (p < 0.001). Six months after SHCL wear, marked morphological changes occurred in the conjunctival epithelium. Tear function tests were also affected, while corneal thickness did not show any significant difference.

Effectiveness of Antimicrobial Peptide Immobilization for Preventing Perioperative Cornea Implant-Associated Bacterial Infection

PubMed Central

Tan, Xiao Wei; Goh, Tze Wei; Saraswathi, P.; Nyein, Chan Lwin; Setiawan, Melina; Riau, Andri; Lakshminarayanan, R.; Liu, Shouping; Tan, Donald; Beuerman, Roger W.

2014-01-01

Titanium (Ti) is a promising candidate biomaterial for an artificial corneal skirt. Antimicrobial peptide (AMP) immobilization may improve the bactericidal effect of the Ti substrate. In this study, we tested the bactericidal efficacy of a functionalized Ti surface in a rabbit keratitis model. A corneal stromal pocket was created by a femtosecond laser. The Ti films were then inserted into the pocket, and Staphylococcus aureus or Pseudomonas aeruginosa was inoculated into the pocket above the implant films. The corneas with Ti-AMP implants were compared with the corneas implanted with unprotected Ti by slit lamp observation and anterior segment optical coherence tomography (AS-OCT). Inflammatory responses were evaluated by bacterium counting, hematoxylin-eosin staining, and immunostaining. There was a lower incidence and a lesser extent of infection on rabbit corneas with Ti-AMP implants than on those with unprotected Ti implants. The bactericidal effect of AMP against S. aureus was comparable to that of postoperative prophylactic antibiotic treatment; hence, SESB2V AMP bound to the Ti implant provided functional activity in vivo, but its efficacy was greater against S. aureus than against P. aeruginosa. This work suggests that SESB2V AMP can be successfully functionalized in a rabbit keratitis model to prevent perioperative corneal infection. PMID:24957820

Ocular dimensions, corneal thickness, and corneal curvature in quarter horses with hereditary equine regional dermal asthenia.

PubMed

Badial, Peres R; Cisneros-Àlvarez, Luis Emiliano; Brandão, Cláudia Valéria S; Ranzani, José Joaquim T; Tomaz, Mayana A R V; Machado, Vania M; Borges, Alexandre S

2015-09-01

The aim of this study was to compare ocular dimensions, corneal curvature, and corneal thickness between horses affected with hereditary equine regional dermal asthenia (HERDA) and unaffected horses. Five HERDA-affected quarter horses and five healthy control quarter horses were used. Schirmer's tear test, tonometry, and corneal diameter measurements were performed in both eyes of all horses prior to ophthalmologic examinations. Ultrasonic pachymetry was performed to measure the central, temporal, nasal, dorsal, and ventral corneal thicknesses in all horses. B-mode ultrasound scanning was performed on both eyes of each horse to determine the dimensions of the ocular structures and to calculate the corneal curvature. Each corneal region examined in this study was thinner in the affected group compared with the healthy control group. However, significant differences in corneal thickness were only observed for the central and dorsal regions. HERDA-affected horses exhibited significant increases in corneal curvature and corneal diameter compared with unaffected animals. The ophthalmologic examinations revealed mild corneal opacity in one eye of one affected horse and in both eyes of three affected horses. No significant between-group differences were observed for Schirmer's tear test, intraocular pressure, or ocular dimensions. Hereditary equine regional dermal asthenia-affected horses exhibit decreased corneal thickness in several regions of the cornea, increased corneal curvature, increased corneal diameter, and mild corneal opacity. Additional research is required to determine whether the increased corneal curvature significantly impacts the visual accuracy of horses with HERDA. © 2014 American College of Veterinary Ophthalmologists.

Corneal dystrophies

PubMed Central

Klintworth, Gordon K

2009-01-01

The term corneal dystrophy embraces a heterogenous group of bilateral genetically determined non-inflammatory corneal diseases that are restricted to the cornea. The designation is imprecise but remains in vogue because of its clinical value. Clinically, the corneal dystrophies can be divided into three groups based on the sole or predominant anatomical location of the abnormalities. Some affect primarily the corneal epithelium and its basement membrane or Bowman layer and the superficial corneal stroma (anterior corneal dystrophies), the corneal stroma (stromal corneal dystrophies), or Descemet membrane and the corneal endothelium (posterior corneal dystrophies). Most corneal dystrophies have no systemic manifestations and present with variable shaped corneal opacities in a clear or cloudy cornea and they affect visual acuity to different degrees. Corneal dystrophies may have a simple autosomal dominant, autosomal recessive or X-linked recessive Mendelian mode of inheritance. Different corneal dystrophies are caused by mutations in the CHST6, KRT3, KRT12, PIP5K3, SLC4A11, TACSTD2, TGFBI, and UBIAD1 genes. Knowledge about the responsible genetic mutations responsible for these disorders has led to a better understanding of their basic defect and to molecular tests for their precise diagnosis. Genes for other corneal dystrophies have been mapped to specific chromosomal loci, but have not yet been identified. As clinical manifestations widely vary with the different entities, corneal dystrophies should be suspected when corneal transparency is lost or corneal opacities occur spontaneously, particularly in both corneas, and especially in the presence of a positive family history or in the offspring of consanguineous parents. Main differential diagnoses include various causes of monoclonal gammopathy, lecithin-cholesterol-acyltransferase deficiency, Fabry disease, cystinosis, tyrosine transaminase deficiency, systemic lysosomal storage diseases (mucopolysaccharidoses, lipidoses, mucolipidoses), and several skin diseases (X-linked ichthyosis, keratosis follicularis spinolosa decalvans). The management of the corneal dystrophies varies with the specific disease. Some are treated medically or with methods that excise or ablate the abnormal corneal tissue, such as deep lamellar endothelial keratoplasty (DLEK) and phototherapeutic keratectomy (PTK). Other less debilitating or asymptomatic dystrophies do not warrant treatment. The prognosis varies from minimal effect on the vision to corneal blindness, with marked phenotypic variability. PMID:19236704

Treatment of Inherited Eye Defects by Systemic Hematopoietic Stem Cell Transplantation.

PubMed

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.

Dry eye disease after refractive surgery: comparative outcomes of small incision lenticule extraction versus LASIK.

PubMed

Denoyer, Alexandre; Landman, Elise; Trinh, Liem; Faure, Jean-François; Auclin, François; Baudouin, Christophe

2015-04-01

To compare small incision lenticule extraction (SMILE) versus LASIK for post-refractive dry eye disease. Prospective, comparative, nonrandomized clinical study. Thirty patients scheduled for bilateral myopic SMILE and 30 age-, sex-, and refraction-matched patients scheduled for bilateral myopic LASIK were enrolled and followed for 6 months after the surgery. Complete evaluation of dry eye disease was performed at 1 and 6 months postoperatively, which included vision-related quality of life (Ocular Surface Disease Index [OSDI]), clinical examinations (tear film breakup time [TBUT], Schirmer I test, corneal staining), and tear osmolarity measurements, together with an overall severity score. Function and morphology of the corneal innervation were evaluated by corneal esthesiometry and subbasal nerve imaging using in vivo confocal microscopy (IVCM). Overall analysis of dry eye disease and corneal innervation. High incidence of mild to moderate dry eye disease was observed in both groups 1 month postoperatively, which remained significantly higher in the LASIK group than in the SMILE group 6 months after surgery (overall severity score [0-4]: 1.2±1.1 vs. 0.2±0.4, respectively, P < 0.01), leading to more frequent use of tear substitutes over the long term. Corneal sensitivity was better in SMILE than in LASIK eyes 1 month postoperatively (3.5±1.79 vs. 2.45±2.48, respectively, P < 0.01) and then recovered to statistically similar values at 6 months. Corneal nerve density, number of long fibers, and branchings as assessed by IVCM were significantly higher in the SMILE group compared with the LASIK group 1 and 6 months after surgery. Corneal sensitivity was negatively correlated with dry eye-related corneal damage (R² = 0.48, P < 0.01), and the long fiber nerve density was independently correlated with the OSDI score (R² = 0.50, P < 0.01) and the Schirmer test (R² = 0.21, P < 0.01) 6 months postoperatively. The SMILE procedure has a less pronounced impact on the ocular surface and corneal innervation compared with LASIK, further reducing the incidence of dry eye disease and subsequent degradation in quality of life after refractive surgery. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Lacritin and Other New Proteins of the Lacrimal Functional Unit

PubMed Central

McKown, Robert L.; Wang, Ningning; Raab, Ronald W.; Karnati, Roy; Zhang, Yinghui; Williams, Patricia B.; Laurie, Gordon W.

2009-01-01

The lacrimal functional unit (LFU) is defined by the 2007 International Dry Eye WorkShop as ‘an integrated system comprising the lacrimal glands, ocular surface (cornea, conjunctiva and meibomian glands) and lids, and the sensory and motor nerves that connect them’. The LFU maintains a healthy ocular surface primarily through a properly functioning tear film that provides protection, lubrication, and an environment for corneal epithelial cell renewal. LFU cells express thousands of proteins. Over two hundred new LFU proteins have been discovered in the last decade. Lacritin is a new LFU-specific growth factor in human tears that flows through ducts to target corneal epithelial cells on the ocular surface. When applied topically in rabbits, lacritin appears to increase the volume of basal tear secretion. Lacritin is one of only a handful of tear proteins preliminarily reported to be downregulated in blepharitis and in two dry eye syndromes. Computational analysis predicts an ordered C-terminal domain that binds the corneal epithelial cell surface proteoglycan syndecan-1 (SDC1) and is required for lacritin’s low nanomolar mitogenic activity. The lacritin binding site on the N-terminus of SDC1 is exposed by heparanase. Heparanase is constitutively expressed by the corneal epithelium and appears to be a normal constituent of tears. Binding triggers rapid signaling to downstream NFAT and mTOR. A wealth of other new proteins, originally designated as hypothetical when first identified by genomic sequencing, are expressed by the human LFU including: ALS2CL, ARHGEF19, KIAA1109, PLXNA1, POLG, WIPI1 and ZMIZ2. Their demonstrated or implied roles in human genetic disease or basic cellular functions are fuel for new investigation. Addressing topical areas in ocular surface physiology with new LFU proteins may reveal interesting new biological mechanisms and help get to the heart of ocular surface dysfunction. PMID:18840430

Collagen cross-linking using riboflavin and ultraviolet-a for corneal thinning disorders: an evidence-based analysis.

PubMed

Pron, G; Ieraci, L; Kaulback, K

2011-01-01

The main objectives for this evidence-based analysis were to determine the safety and effectiveness of photochemical corneal collagen cross-linking with riboflavin (vitamin B(2)) and ultraviolet-A radiation, referred to as CXL, for the management of corneal thinning disease conditions. The comparative safety and effectiveness of corneal cross-linking with other minimally invasive treatments such as intrastromal corneal rings was also reviewed. The Medical Advisory Secretariat (MAS) evidence-based analysis was performed to support public financing decisions. SUBJECT OF THE EVIDENCE-BASED ANALYSIS: The primary treatment objective for corneal cross-linking is to increase the strength of the corneal stroma, thereby stabilizing the underlying disease process. At the present time, it is the only procedure that treats the underlying disease condition. The proposed advantages for corneal cross-linking are that the procedure is minimally invasive, safe and effective, and it can potentially delay or defer the need for a corneal transplant. In addition, corneal cross-linking does not adversely affect subsequent surgical approaches, if they are necessary, or interfere with corneal transplants. The evidence for these claims for corneal cross-linking in the management of corneal thinning disorders such as keratoconus will be the focus of this review. The specific research questions for the evidence review were as follows: TECHNICAL: How technically demanding is corneal cross-linking and what are the operative risks? What is known about the broader safety profile of corneal cross-linking?Effectiveness - Corneal Surface Topographic Affects:What are the corneal surface remodeling effects of corneal cross-linking?Do these changes interfere with subsequent interventions, particularly corneal transplant known as penetrating keratoplasty (PKP)?Effectiveness -Visual Acuity:What impacts does the remodeling have on visual acuity?Are these impacts predictable, stable, adjustable and durable?Effectiveness - Refractive Outcomes: What impact does remodeling have on refractive outcomes?Effectiveness - Visual Quality (Symptoms): What impact does corneal cross-linking have on vision quality such as contrast vision, and decreased visual symptoms (halos, fluctuating vision)?Effectiveness - Contact lens tolerance: To what extent does contact lens intolerance improve after corneal cross-linking?Vision-Related QOL: What is the impact of corneal cross-linking on functional visual rehabilitation and quality of life?PATIENT SATISFACTION: Are patients satisfied with their vision following the procedure?Disease Process:What impact does corneal cross-linking have on the underling corneal thinning disease process?Does corneal cross-linking delay or defer the need for a corneal transplant?What is the comparative safety and effectiveness of corneal cross-linking compared with other minimally invasive treatments for corneal ectasia such as intrastromal corneal rings? TARGET POPULATION AND CONDITION Corneal ectasia (thinning) disorders represent a range of disorders involving either primary disease conditions, such as keratoconus (KC) and pellucid marginal corneal degeneration, or secondary iatrogenic conditions, such as corneal thinning occurring after laser in situ keratomileusis (LASIK) refractive surgery. Corneal thinning is a disease that occurs when the normally round dome-shaped cornea progressively thins causing a cone-like bulge or forward protrusion in response to the normal pressure of the eye. The thinning occurs primarily in the stroma layers and is believed to be a breakdown in the collagen process. This bulging can lead to irregular astigmatism or shape of the cornea. Because the anterior part of the cornea is responsible for most of the focusing of the light on the retina, this can then result in loss of visual acuity. The reduced visual acuity can make even simple daily tasks, such as driving, watching television or reading, difficult to perform. Keratoconus is the most common form of corneal thinning disorder and involves a noninflammatory chronic disease process of progressive corneal thinning. Although the specific cause for the biomechanical alterations in the corneal stroma is unknown, there is a growing body of evidence suggesting that genetic factors may play an important role. Keratoconus is a rare disease (< 0.05% of the population) and is unique among chronic eye diseases because it has an early onset, with a median age of 25 years. Disease management for this condition follows a step-wise approach depending on disease severity. Contact lenses are the primary treatment of choice when there is irregular astigmatism associated with the disease. Patients are referred for corneal transplants as a last option when they can no longer tolerate contact lenses or when lenses no longer provide adequate vision. Keratoconus is one of the leading indications for corneal transplants and has been so for the last 3 decades. Despite the high success rate of corneal transplants (up to 20 years) there are reasons to defer it as long as possible. Patients with keratoconus are generally young and a longer-term graft survival of at least 30 or 40 years may be necessary. The surgery itself involves lengthy time off work and postsurgery, while potential complications include long-term steroid use, secondary cataracts, and glaucoma. After a corneal transplant, keratoconus may recur resulting in a need for subsequent interventions. Residual refractive errors and astigmatism can remain challenges after transplantation, and high refractive surgery and regraft rates in KC patients have been reported. Visual rehabilitation or recovery of visual acuity after transplant may be slow and/or unsatisfactory to patients. Corneal cross-linking involves the use of riboflavin (vitamin B(2)) and ultraviolet-A (UVA) radiation. A UVA irradiation device known as the CXL® device (license number 77989) by ACCUTECH Medical Technologies Inc. has been licensed by Health Canada as a Class II device since September 19, 2008. An illumination device that emits homogeneous UVA, in combination with any generic form of riboflavin, is licensed by Health Canada for the indication to slow or stop the progression of corneal thinning caused by progressive keratectasia, iatrogenic keratectasia after laser-assisted in situ keratomileusis (LASIK) and pellucid marginal degeneration. The same device is named the UV-X® device by IROCMedical, with approvals in Argentina, the European Union and Australia. UVA devices all use light emitting diodes to generate UVA at a wavelength of 360-380 microns but vary in the number of diodes (5 to 25), focusing systems, working distance, beam diameter, beam uniformity and extent to which the operator can vary the parameters. In Ontario, CXL is currently offered at over 15 private eye clinics by refractive surgeons and ophthalmologists. The treatment is an outpatient procedure generally performed with topical anesthesia. The treatment consists of several well defined procedures. The epithelial cell layer is first removed, often using a blunt spatula in a 9.0 mm diameter under sterile conditions. This step is followed by the application of topical 0.1% riboflavin (vitamin B(2)) solution every 3 to 5 minutes for 25 minutes to ensure that the corneal stroma is fully penetrated. A solid-state UVA light source with a wavelength of 370 nm (maximum absorption of riboflavin) and an irradiance of 3 mW/cm(2) is used to irradiate the central cornea. Following treatment, a soft bandage lens is applied and prescriptions are given for oral pain medications, preservative-free tears, anti-inflammatory drops (preferably not nonsteroidal anti-inflammatory drugs, or NSAIDs) and antibiotic eye drops. Patients are recalled 1 week following the procedure to evaluate re-epithelialization and they are followed-up subsequently. A literature search was conducted on photochemical corneal collagen cross-linking with riboflavin (vitamin B(2)) and ultraviolet-A for the management of corneal thinning disorders using a search strategy with appropriate keywords and subject headings for CXL for literature published up until April 17, 2011. The literature search for this Health Technology Assessment (HTA) review was performed using the Cochrane Library, the Emergency Care Research Institute (ECRI) and the Centre for Reviews and Dissemination. The websites of several other health technology agencies were also reviewed, including the Canadian Agency for Drugs and Technologies in Health (CADTH) and the United Kingdom's National Institute for Clinical Excellence (NICE). The databases searched included OVID MEDLINE, MEDLINE IN-Process and other Non-Indexed Citations such as EMBASE. As the evidence review included an intervention for a rare condition, case series and case reports, particularly for complications and adverse events, were reviewed. A total of 316 citations were identified and all abstracts were reviewed by a single reviewer for eligibility. For those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. (ABSTRACT TRUNCATED)

Use of specular microscopy to determine corneal endothelial cell morphology and morphometry in enucleated cat eyes.

PubMed

Franzen, Angela A; Pigatto, João A T; Abib, Fernando C; Albuquerque, Luciane; Laus, José L

2010-07-01

The purpose of this study was to investigate the effect of age on endothelial morphology and morphometry in cats. The corneal endothelium was studied using a contact specular microscope. A total of 18 cats (Felis catus Linnaeus, 1758) were evaluated in this study. The subjects were divided into three groups of six cats each in function of age: G1 (1 to 3 months old), G2 (5 to 12 months old), and G3 (24 to 40 months old). The examination presented data as endothelial cell density (ECD), average cell area, corneal thickness, polymegathism, and pleomorphism. Results revealed ECD decrease in corneas of normal cats with age, as well as a corresponding increase in endothelial cell area and pleomorphism. The present work suggests that the endothelial parameters evaluated change with advancing age.

Quality of Life and Mental State After Sight Restoration by Corneal Transplantation.

PubMed

Drzyzga, Karolina; Krupka-Matuszczyk, Irena; Drzyzga, Łukasz; Mrukwa-Kominek, Ewa; Kucia, Krzysztof

2016-01-01

Quality of life has frequently been reported to improve after corneal transplantation. However, mental status before and after surgery has until now been less well investigated. The aim of this study was to investigate quality of life and mental status before and after corneal transplantation including postoperative immunosuppression and visual acuity. A total of 45 patients were assessed before, and 3 weeks and 4 months after transplantation using the following questionnaires: Visual Function Questionnaire, Beck Depression Inventory, and Hamilton Anxiety Rating Scale. Assessment included a visual acuity test using the logMAR chart, and recognition of the role of postoperative immunosuppression. Finally, patients were asked if they would be willing to have the surgery again. In the candidates for surgery, quality of life was reduced, and symptoms of depression and anxiety were present. Corneal transplantation improved their quality of life and reduced symptoms of depression and anxiety. Changes in quality of life and in mental state were associated with a change in visual acuity in the grafted eye. Higher doses of prednisone were associated with a worse quality of life and with more severe symptoms of depression and anxiety after transplantation. Further, 82.5% of patients would have the surgery again. Assessment for psychiatric symptoms should be considered in individuals facing corneal surgery. Copyright © 2016 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Control of Scar Tissue Formation in the Cornea: Strategies in Clinical and Corneal Tissue Engineering

PubMed Central

Wilson, Samantha L.; El Haj, Alicia J.; Yang, Ying

2012-01-01

Corneal structure is highly organized and unified in architecture with structural and functional integration which mediates transparency and vision. Disease and injury are the second most common cause of blindness affecting over 10 million people worldwide. Ninety percent of blindness is permanent due to scarring and vascularization. Scarring caused via fibrotic cellular responses, heals the tissue, but fails to restore transparency. Controlling keratocyte activation and differentiation are key for the inhibition and prevention of fibrosis. Ophthalmic surgery techniques are continually developing to preserve and restore vision but corneal regression and scarring are often detrimental side effects and long term continuous follow up studies are lacking or discouraging. Appropriate corneal models may lead to a reduced need for corneal transplantation as presently there are insufficient numbers or suitable tissue to meet demand. Synthetic optical materials are under development for keratoprothesis although clinical use is limited due to implantation complications and high rejection rates. Tissue engineered corneas offer an alternative which more closely mimic the morphological, physiological and biomechanical properties of native corneas. However, replication of the native collagen fiber organization and retaining the phenotype of stromal cells which prevent scar-like tissue formation remains a challenge. Careful manipulation of culture environments are under investigation to determine a suitable environment that simulates native ECM organization and stimulates keratocyte migration and generation. PMID:24955637

Corneal topography measurements for biometric applications

NASA Astrophysics Data System (ADS)

Lewis, Nathan D.

The term biometrics is used to describe the process of analyzing biological and behavioral traits that are unique to an individual in order to confirm or determine his or her identity. Many biometric modalities are currently being researched and implemented including, fingerprints, hand and facial geometry, iris recognition, vein structure recognition, gait, voice recognition, etc... This project explores the possibility of using corneal topography measurements as a trait for biometric identification. Two new corneal topographers were developed for this study. The first was designed to function as an operator-free device that will allow a user to approach the device and have his or her corneal topography measured. Human subject topography data were collected with this device and compared to measurements made with the commercially available Keratron Piccolo topographer (Optikon, Rome, Italy). A third topographer that departs from the standard Placido disk technology allows for arbitrary pattern illumination through the use of LCD monitors. This topographer was built and tested to be used in future research studies. Topography data was collected from 59 subjects and modeled using Zernike polynomials, which provide for a simple method of compressing topography data and comparing one topographical measurement with a database for biometric identification. The data were analyzed to determine the biometric error rates associated with corneal topography measurements. Reasonably accurate results, between three to eight percent simultaneous false match and false non-match rates, were achieved.

Time-dependent LXR/RXR pathway modulation characterizes capillary remodeling in inflammatory corneal neovascularization.

PubMed

Mukwaya, Anthony; Lennikov, Anton; Xeroudaki, Maria; Mirabelli, Pierfrancesco; Lachota, Mieszko; Jensen, Lasse; Peebo, Beatrice; Lagali, Neil

2018-05-01

Inflammation in the normally immune-privileged cornea can initiate a pathologic angiogenic response causing vision-threatening corneal neovascularization. Inflammatory pathways, however, are numerous, complex and are activated in a time-dependent manner. Effective resolution of inflammation and associated angiogenesis in the cornea requires knowledge of these pathways and their time dependence, which has, to date, remained largely unexplored. Here, using a model of endogenous resolution of inflammation-induced corneal angiogenesis, we investigate the time dependence of inflammatory genes in effecting capillary regression and the return of corneal transparency. Endogenous capillary regression was characterized by a progressive thinning and remodeling of angiogenic capillaries and inflammatory cell retreat in vivo in the rat cornea. By whole-genome longitudinal microarray analysis, early suppression of VEGF ligand-receptor signaling and inflammatory pathways preceded an unexpected later-phase preferential activation of LXR/RXR, PPARα/RXRα and STAT3 canonical pathways, with a concurrent attenuation of LPS/IL-1 inhibition of RXR function and Wnt/β-catenin signaling pathways. Potent downstream inflammatory cytokines such as Cxcl5, IL-1β, IL-6 and Ccl2 were concomitantly downregulated during the remodeling phase. Upstream regulators of the inflammatory pathways included Socs3, Sparc and ApoE. A complex and coordinated time-dependent interplay between pro- and anti-inflammatory signaling pathways highlights a potential anti-inflammatory role of LXR/RXR, PPARα/RXRα and STAT3 signaling pathways in resolving inflammatory corneal angiogenesis.

Transport mechanism of chitosan-N-acetylcysteine, chitosan oligosaccharides or carboxymethyl chitosan decorated coumarin-6 loaded nanostructured lipid carriers across the rabbit ocular.

PubMed

Li, Jinyu; Tan, Guoxin; Cheng, Bingchao; Liu, Dandan; Pan, Weisan

2017-11-01

To facilitate the hydrophobic drugs modeled by coumarin-6 (Cou-6) acrossing the cornea to the anterior chamber of the rabbit eye, chitosan (CS) derivatives including chitosan-N-acetyl-l-cysteine (CS-NAC), chitosan oligosaccharides (COS) and carboxymethyl chitosan (CMCS) modified nanostructured lipid carriers (NLCs) were designed and characterized. We found that, with similar size distribution and positivecharges, different CS derivatives based on NLCs led to distinctive delivery performance. In vivo precorneal retention study on rabbits revealed that these CS derivatives coating exhibited a stronger resistant effect than Cou-6 eye drops and Cou-6-NLC (P<0.05), moreover, the AUC (0-∞) , C max and MRT (0-∞) of them followed the sequence of CMCS-Cou-6-NLC

Ocular effects of exposure to triethylamine in the sand core cold box of a foundry.

PubMed Central

Reilly, M J; Rosenman, K D; Abrams, J H; Zhu, Z; Tseng, C; Hertzberg, V; Rice, C

1995-01-01

OBJECTIVES--To assess the acute and chronic ophthalmological effects of triethylamine exposure among foundry workers. METHODS--Ocular effects on people currently, previously, and never exposed to triethylamine in a foundry cold box were studied at two points in time. The initial phase included an ocular examination with a slit lamp to assess corneal health, a visual acuity test, and a questionnaire to assess vision symptoms. The follow up included measurements of corneal thickness with an ultrasonic pachymeter and the vision symptoms questionnaire before and after the shift and at the beginning and end of the week. Personal air measurements for triethylamine were also obtained during the follow up. RESULTS--The vision symptoms of blurriness, halos around lights, and blue hazy vision occurred more often in currently exposed workers than those previously or never exposed to triethylamine. Air concentrations of triethylamine ranged from < 0.33 mg/m3 to 20.3 mg/m3. Among currently exposed workers, symptoms were more common among those with exposure to > 10 mg/m3 of triethylamine (odds ratio (OR) = 3.0, 95% confidence interval (95% CI) 0.35-25.6). No differences in corneal thickness were found in currently or previously exposed workers and those never exposed. No increase in corneal thickness was found after v before the shift. CONCLUSION--Despite low concentrations of triethylamine and no corneal oedema, workers exposed to triethylamine reported vision symptoms. Possible explanations for these symptoms without corneal oedema are that triethylamine affects ciliary muscle function or that the corneal oedema was transient and not present when corneal thickness measurements were taken. No chronic effects were found in previously exposed workers. Further research is needed to elucidate the mechanism for the reported vision symptoms, which occurred below the current United States eight hour time weighted standard of 100 mg/m3 and the American Conference of Governmental Industrial Hygienists (ACGIH) recommended value at the time of our study of 40 mg/m3. We recommend that air concentrations be maintained to meet the current recommended ACGIH threshold of 4.1 mg/m3. PMID:7795757

Spontaneous Corneal Hydrops in a Patient with a Corneal Ulcer

PubMed Central

Batawi, Hatim; Kothari, Nikisha; Camp, Andrew; Bernhard, Luis; Karp, Carol L.; Galor, Anat

2016-01-01

Purpose We report the case of a 77-year-old man with no history of keratoconus or other ectatic disorders who presented with corneal hydrops in the setting of a corneal ulcer. The risk factors, pathogenesis and treatment options of corneal hydrops are discussed. Method This is an observational case report study. Results A 77-year-old man presented with a 1-day history of severe pain, redness, mucous discharge and photophobia in the right eye. A slit-lamp examination of the right eye showed an area of focal corneal edema and protrusion. Within the area of edema and protrusion, there was an infiltrate with an overlying epithelial defect consistent with an infectious corneal ulcer. The Seidel test showed no leakage, so a clinical diagnosis of corneal hydrops associated with nonperforated corneal ulcer was made. With appropriate antibiotic treatment, the corneal ulcer and hydrops both resolved over a 1-month period. Conclusion Corneal hydrops can occur in the setting of corneal infections. PMID:26889160

Spontaneous Corneal Hydrops in a Patient with a Corneal Ulcer.

PubMed

Batawi, Hatim; Kothari, Nikisha; Camp, Andrew; Bernhard, Luis; Karp, Carol L; Galor, Anat

2016-01-01

We report the case of a 77-year-old man with no history of keratoconus or other ectatic disorders who presented with corneal hydrops in the setting of a corneal ulcer. The risk factors, pathogenesis and treatment options of corneal hydrops are discussed. This is an observational case report study. A 77-year-old man presented with a 1-day history of severe pain, redness, mucous discharge and photophobia in the right eye. A slit-lamp examination of the right eye showed an area of focal corneal edema and protrusion. Within the area of edema and protrusion, there was an infiltrate with an overlying epithelial defect consistent with an infectious corneal ulcer. The Seidel test showed no leakage, so a clinical diagnosis of corneal hydrops associated with nonperforated corneal ulcer was made. With appropriate antibiotic treatment, the corneal ulcer and hydrops both resolved over a 1-month period. Corneal hydrops can occur in the setting of corneal infections.

Functional lacrimal gland regeneration by transplantation of a bioengineered organ germ

PubMed Central

Hirayama, Masatoshi; Ogawa, Miho; Oshima, Masamitsu; Sekine, Yurie; Ishida, Kentaro; Yamashita, Kentaro; Ikeda, Kazutaka; Shimmura, Shigeto; Kawakita, Tetsuya; Tsubota, Kazuo; Tsuji, Takashi

2013-01-01

The lacrimal gland has a multifaceted role in maintaining a homeostatic microenvironment for a healthy ocular surface via tear secretion. Dry-eye disease, which is caused by lacrimal gland dysfunction, is one of the most prevalent eye diseases that cause corneal epithelial damage and results in significant loss of vision and a reduction in the quality of life. Here we demonstrate orthotopic transplantation of bioengineered lacrimal gland germs into adult mice with an extra-orbital lacrimal gland defect, a mouse model that mimics the corneal epithelial damage caused by lacrimal gland dysfunction. The bioengineered lacrimal gland germs and harderian gland germs both develop in vivo and achieve sufficient physiological functionality, including tear production in response to nervous stimulation and ocular surface protection. This study demonstrates the potential for bioengineered organ replacement to functionally restore the lacrimal gland. PMID:24084941

Traumatic corneal flap displacement after laser in situ keratomileusis (LASIK)

PubMed Central

Tsai, Tsung-Han; Peng, Kai-Ling; Lin, Chien-Jen

2017-01-01

Background Laser in situ keratomileusis (LASIK) is the most common and popular procedure performed for the correction of refractive errors in the last two decades. We report a case of traumatic flap displacement with flap folding which occurred 3 years after LASIK was performed. Previous literature suggests that vision prognosis would be closely related to proper and prompt management of traumatic flap displacement with flap folding 3 years after LASIK. Case presentation A 23-year-old female presented to our hospital who had undergone uneventful LASIK in both eyes 3 years prior. Unfortunately, she had suffered a blunt trauma in her right eye in a car accident. A late onset of corneal flap displacement was found with upper and lower portion of the flap being folded inside the corneal bed. Surgical intervention for debridement with subsequent reposition of corneal flap was performed as soon as possible in the operating room. A bandage contact lens was placed, and topical antibiotic and corticosteroids were given postoperatively. Two days after the operation, the displaced corneal flap was found to be well attached smoothly on the corneal bed without folds. The best-corrected visual acuity was 6/6 with refraction of −0.75 D to 1.0 D ×175° in her right eye 1 month later. Literature review We reviewed a total of 19 published cases of late-onset traumatic flap dislocations or displacements after LASIK with complete data from 2000 to 2014. Conclusion Traumatic displacement of corneal flaps after LASIK may occur after blunt injury with specific direction of force to the flap margin, especially tangential one. According to the previous literature, late-onset traumatic flap displacement may happen at any time after LASIK and be caused by various types of injuries. Fortunately, good visual function could mostly be restored with immediate and proper management. PMID:28458585

Oxygen transport through soft contact lens and cornea: Lens characterization and metabolic modeling

NASA Astrophysics Data System (ADS)

Chhabra, Mahendra

The human cornea requires oxygen to sustain metabolic processes critical for its normal functioning. Any restriction to corneal oxygen supply from the external environment (e.g., by wearing a low oxygen-permeability contact lens) can lead to hypoxia, which may cause corneal edema (swelling), limbal hyperemia, neovascularization, and corneal acidosis. The need for adequate oxygen to the cornea is a major driving force for research and development of hypertransmissible soft contact lenses (SCLs). Currently, there is no standard technique for measuring oxygen permeability (Dk) of hypertransmissible silicone-hydrogel SCLs. In this work, an electrochemistry-based polarographic apparatus was designed, built, and operated to measure oxygen permeability in hypertransmissible SCLs. Unlike conventional methods where a range of lens thickness is needed for determining oxygen permeabilities of SCLs, this apparatus requires only a single lens thickness. The single-lens permeameter provides a reliable, efficient, and economic tool for measuring oxygen permeabilities of commercial hypertransmissible SCLs. The single-lens permeameter measures not only the product Dk, but, following modification, it measures separately diffusivity, D, and solubility, k, of oxygen in hypertransmissible SCLs. These properties are critical for designing better lens materials that ensure sufficient oxygen supply to the cornea. Metabolism of oxygen in the cornea is influenced by contact-lens-induced hypoxia, diseases such as diabetes, surgery, and drug treatment, Thus, estimation of the in-vivo corneal oxygen consumption rate is essential for gauging adequate oxygen supply to the cornea. Therefore, we have developed an unsteady-state reactive-diffusion model for the cornea-contact-lens system to determine in-vivo human corneal oxygen-consumption rate. Finally, a metabolic model was developed to determine the relation between contact-lens oxygen transmissibility (Dk/L) and corneal oxygen deficiency. A new parameter "Oxygen Deficiency Factor" (ODF) is defined to quantify oxygen deficiency in local regions of the cornea. We use this concept to determine the minimum required contact-lens oxygen transmissibility, Dk/L = 150 Barrer/cm, to avoid hypoxia-induced corneal physiologic complications.

Hevin Plays a Pivotal Role in Corneal Wound Healing

PubMed Central

Chaurasia, Shyam S.; Perera, Promoda R.; Poh, Rebekah; Lim, Rayne R.; Wong, Tina T.; Mehta, Jodhbir S.

2013-01-01

Background Hevin is a matricellular protein involved in tissue repair and remodeling via interaction with the surrounding extracellular matrix (ECM) proteins. In this study, we examined the functional role of hevin using a corneal stromal wound healing model achieved by an excimer laser-induced irregular phototherapeutic keratectomy (IrrPTK) in hevin-null (hevin-/-) mice. We also investigated the effects of exogenous supplementation of recombinant human hevin (rhHevin) to rescue the stromal cellular components damaged by the excimer laser. Methodology/Principal Findings Wild type (WT) and hevin -/- mice were divided into three groups at 4 time points- 1, 2, 3 and 4 weeks. Group I served as naïve without any treatment. Group II received epithelial debridement and underwent IrrPTK using excimer laser. Group III received topical application of rhHevin after IrrPTK surgery for 3 days. Eyes were analyzed for corneal haze and matrix remodeling components using slit lamp biomicroscopy, in vivo confocal microscopy, light microscopy (LM), transmission electron microscopy (TEM), immunohistochemistry (IHC) and western blotting (WB). IHC showed upregulation of hevin in IrrPTK-injured WT mice. Hevin -/- mice developed corneal haze as early as 1-2 weeks post IrrPTK-treatment compared to the WT group, which peaked at 3-4 weeks. They also exhibited accumulation of inflammatory cells, fibrotic components of ECM proteins and vascularized corneas as seen by IHC and WB. LM and TEM showed activated keratocytes (myofibroblasts), inflammatory debris and vascular tissues in the stroma. Exogenous application of rhHevin for 3 days reinstated inflammatory index of the corneal stroma similar to WT mice. Conclusions/Significance Hevin is transiently expressed in the IrrPTK-injured corneas and loss of hevin predisposes them to aberrant wound healing. Hevin -/- mice develop early corneal haze characterized by severe chronic inflammation and stromal fibrosis that can be rescued with exogenous administration of rhHevin. Thus, hevin plays a pivotal role in the corneal wound healing. PMID:24303054

Recurrent Corneal Erosions in Corneal Dystrophies: a Review of the Pathogenesis, Differential Diagnosis, and Therapy.

PubMed

Omari, Amro A; Mian, Shahzad I

2018-06-01

Recurrent corneal erosions in corneal dystrophies are visually significant and bothersome to patients. The goal of this article is to review the pathogenesis, differential diagnosis, and management of recurrent corneal erosions in corneal dystrophies. Forty-eight articles and 1 textbook recently published on corneal erosions in corneal dystrophies were reviewed. The findings on the pathogenesis and clinical characteristics of erosions in each dystrophy were summarized. Any contradicting opinions for which the literature was unclear were either omitted or recorded as lacking strong evidence. The epithelial-stromal complex plays an important role in the pathogenesis of erosions in corneal dystrophies. The clinical features of each corneal dystrophy guide their diagnosis and management. A better understanding of the pathogenesis and clinical features of erosions in corneal dystrophies can lead to better clinical outcomes. Georg Thieme Verlag KG Stuttgart · New York.

The Impact of Inoculation Parameters on the Pathogenesis of Contact Lens–Related Infectious Keratitis

PubMed Central

Tam, Connie; Mun, James J.; Evans, David J.

2010-01-01

Purpose. Contact lens wear predisposes to Pseudomonas aeruginosa keratitis, but the mechanisms involved remain unclear. An in vivo model was used to study lens inoculation conditions enabling disease. Methods. Custom-made hydrogel contact lenses were fitted to rats after incubation in P. aeruginosa approximately 1011 cfu/mL (3 hours) or approximately 103 cfu/mL (24 hours). Another group was inadvertently inoculated with a suction pen previously used with high inocula, but rinsed in ethanol and stored dry (6 months). Some corneas were tissue paper–blotted to cause fluorescein staining before lens fitting. Contralateral eyes were untreated. Twenty-four hours after disease detection, lenses were transferred to naive rats or examined by confocal microscopy before homogenization to quantify viable bacteria. After lens removal, corneas were washed to collect nonadherent bacteria and were analyzed by immunohistochemistry. Results. All eyes challenged with unworn contaminated lenses developed keratitis after approximately 7 to 10 days. Disease delay and severity were unaffected by inoculum parameters or tissue blotting but occurred sooner with lenses transferred from infected eyes (∼2 days). Worn lenses and corneal washes contained infecting bacteria. Posterior, not anterior, lens surfaces harbored P. aeruginosa biofilms that penetrated the lens matrix. Diseased corneas showed an infiltration of phagocytes and T-lymphocytes. Conclusions. P. aeruginosa induces keratitis in this lens-wearing model after a single inoculation. Delayed disease onset was interesting considering the greater keratitis risk during extended wear. Infection did not require the disruption of corneal barrier function before lens wear and occurred without exposure to lens care solutions. The data suggest that keratitis involves biofilm formation or other bacterial adaptations in vivo. PMID:20130275

Influence of corneal hydration on optical coherence elastography

NASA Astrophysics Data System (ADS)

Twa, Michael D.; Vantipalli, Srilatha; Singh, Manmohan; Li, Jiasong; Larin, Kirill V.

2016-03-01

Corneal biomechanical properties are influenced by several factors, including intraocular pressure, corneal thickness, and viscoelastic responses. Corneal thickness is directly proportional to tissue hydration and can influence corneal stiffness, but there is no consensus on the magnitude or direction of this effect. We evaluated the influence of corneal hydration on dynamic surface deformation responses using optical coherence elastography (OCE). Fresh rabbit eyes (n=10) were prepared by removing the corneal epithelium and dropping with 0.9% saline every 5 minutes for 1 hour, followed by 20% dextran solution every 5 minutes for one hour. Corneal thickness was determined from structural OCT imaging and OCE measurements were performed at baseline and every 20 minutes thereafter. Micron-scale deformations were induced at the apex of the corneal tissue using a spatially-focused (150μm) short-duration (<1ms) air-pulse delivery system. These dynamic tissue responses were measured non-invasively with a phase-stabilized swept source OCT system. The tissue surface deformation response (Relaxation Rate: RR) was quantified as the time constant, over which stimulated tissue recovered from the maximum deformation amplitude. Elastic wave group velocity (GV) was also quantified and correlated with change in corneal thickness due to hydration process. Corneal thickness rapidly increased and remained constant following epithelium removal and changed little thereafter. Likewise, corneal stiffness changed little over the first hour and then decreased sharply after Dextran application (thickness: -46% [-315/682 μm] RR: - 24% [-0.7/2.88 ms-1]; GV: -19% [-0.6/3.2 m/s]). Corneal thickness and corneal stiffness (RR) were well correlated (R2 = .66). Corneal biomechanical properties are highly correlated with tissue hydration over a wide range of corneal thickness and these changes in corneal stiffness are quantifiable using OCE.

Construction of a Corneal Stromal Equivalent with SMILE-Derived Lenticules and Fibrin Glue

PubMed Central

Yin, Houfa; Qiu, Peijin; Wu, Fang; Zhang, Wei; Teng, Wenqi; Qin, Zhenwei; Li, Chao; Zhou, Jiaojie; Fang, Zhi; Tang, Qiaomei; Fu, Qiuli; Ma, Jian; Yang, Yabo

2016-01-01

The scarcity of corneal tissue to treat deep corneal defects and corneal perforations remains a challenge. Currently, small incision lenticule extraction (SMILE)-derived lenticules appear to be a promising alternative for the treatment of these conditions. However, the thickness and toughness of a single piece of lenticule are limited. To overcome these limitations, we constructed a corneal stromal equivalent with SMILE-derived lenticules and fibrin glue. In vitro cell culture revealed that the corneal stromal equivalent could provide a suitable scaffold for the survival and proliferation of corneal epithelial cells, which formed a continuous pluristratified epithelium with the expression of characteristic markers. Finally, anterior lamellar keratoplasty in rabbits demonstrated that the corneal stromal equivalent with decellularized lenticules and fibrin glue could repair the anterior region of the stroma, leading to re-epithelialization and recovery of both transparency and ultrastructural organization. Corneal neovascularization, graft degradation, and corneal rejection were not observed within 3 months. Taken together, the corneal stromal equivalent with SMILE-derived lenticules and fibrin glue appears to be a safe and effective alternative for the repair of damage to the anterior cornea, which may provide new avenues in the treatment of deep corneal defects or corneal perforations. PMID:27651001

Construction of a Corneal Stromal Equivalent with SMILE-Derived Lenticules and Fibrin Glue.

PubMed

Yin, Houfa; Qiu, Peijin; Wu, Fang; Zhang, Wei; Teng, Wenqi; Qin, Zhenwei; Li, Chao; Zhou, Jiaojie; Fang, Zhi; Tang, Qiaomei; Fu, Qiuli; Ma, Jian; Yang, Yabo

2016-09-21

The scarcity of corneal tissue to treat deep corneal defects and corneal perforations remains a challenge. Currently, small incision lenticule extraction (SMILE)-derived lenticules appear to be a promising alternative for the treatment of these conditions. However, the thickness and toughness of a single piece of lenticule are limited. To overcome these limitations, we constructed a corneal stromal equivalent with SMILE-derived lenticules and fibrin glue. In vitro cell culture revealed that the corneal stromal equivalent could provide a suitable scaffold for the survival and proliferation of corneal epithelial cells, which formed a continuous pluristratified epithelium with the expression of characteristic markers. Finally, anterior lamellar keratoplasty in rabbits demonstrated that the corneal stromal equivalent with decellularized lenticules and fibrin glue could repair the anterior region of the stroma, leading to re-epithelialization and recovery of both transparency and ultrastructural organization. Corneal neovascularization, graft degradation, and corneal rejection were not observed within 3 months. Taken together, the corneal stromal equivalent with SMILE-derived lenticules and fibrin glue appears to be a safe and effective alternative for the repair of damage to the anterior cornea, which may provide new avenues in the treatment of deep corneal defects or corneal perforations.

Component corneal surgery: An update

PubMed Central

Maharana, Prafulla K.; Sahay, Pranita; Singhal, Deepali; Garg, Itika; Titiyal, Jeewan S.; Sharma, Namrata

2017-01-01

Several decades ago, penetrating keratoplasty was a challenge to corneal surgeons. Constant effort by the corneal surgeon to improve the outcomes as well as utilization of the available resources has led to a revolutionary change in the field of keratoplasty. All these efforts have led to the evolution of techniques that allow a corneal surgeon to disease-specific transplant of individual layers of corneal “so-called component corneal surgery” depending on the layer of cornea affected. This has led to an improvement in corneal graft survival as well as a better utilization of corneal tissues. This article reviews the currently available literature on component corneal surgeries and provides an update on the available techniques. PMID:28820150

Turnover of bone marrow-derived cells in the irradiated mouse cornea

PubMed Central

Chinnery, Holly R; Humphries, Timothy; Clare, Adam; Dixon, Ariane E; Howes, Kristen; Moran, Caitlin B; Scott, Danielle; Zakrzewski, Marianna; Pearlman, Eric; McMenamin, Paul G

2008-01-01

In light of an increasing awareness of the presence of bone marrow (BM)-derived macrophages in the normal cornea and their uncertain role in corneal diseases, it is important that the turnover rate of these resident immune cells be established. The baseline density and distribution of macrophages in the corneal stroma was investigated in Cx3cr1gfp transgenic mice in which all monocyte-derived cells express enhanced green fluorescent protein (eGFP). To quantify turnover, BM-derived cells from transgenic eGFP mice were transplanted into whole-body irradiated wild-type recipients. Additionally, wild-type BM-derived cells were injected into irradiated Cx3cr1+/gfp recipients, creating reverse chimeras. At 2, 4 and 8 weeks post-reconstitution, the number of eGFP+ cells in each corneal whole mount was calculated using epifluorescence microscopy, immunofluorescence staining and confocal microscopy. The total density of myeloid-derived cells in the normal Cx3cr1+/gfp cornea was 366 cells/mm2. In BM chimeras 2 weeks post-reconstitution, 24% of the myeloid-derived cells had been replenished and were predominantly located in the anterior stroma. By 8 weeks post-reconstitution 75% of the myeloid-derived cells had been replaced and these cells were distributed uniformly throughout the stroma. All donor eGFP+ cells expressed low to moderate levels of CD45 and CD11b, with approximately 25% coexpressing major histocompatibility complex class II, a phenotype characteristic of previous descriptions of corneal stromal macrophages. In conclusion, 75% of the myeloid-derived cells in the mouse corneal stroma are replenished after 8 weeks. These data provide a strong basis for functional investigations of the role of resident stromal macrophages versus non-haematopoietic cells using BM chimeric mice in models of corneal inflammation. PMID:18540963

Effect of chemical composition on corneal tissue response to photopolymerized materials comprising 2-hydroxyethyl methacrylate and acrylic acid.

PubMed

Lai, Jui-Yang

2014-01-01

The purpose of this work was to investigate the relationship between the feed composition of 2-hydroxyethyl methacrylate (HEMA)/acrylic acid (AAc) and hydrogel material compatibility towards ocular anterior segment tissues, particularly the corneal endothelium. The monomer solutions of HEMA and AAc were mixed at varying volume ratios of 92:0, 87:5, 82:10, 77:15, and 72:20, and were subjected to UV irradiation. Then, the 7-mm-diameter membrane implants made from photopolymerized materials were placed into the ocular anterior chamber for 4days and assessed by biomicroscopic examinations, corneal thickness measurements, and quantitative real-time reverse transcription polymerase chain reaction analyses. The poly(HEMA-co-AAc) implants prepared from the solution mixture containing 0-10vol.% AAc displayed good biocompatibility. However, with increasing volume ratio of AAc and HEMA from 15:77 to 20:72, the enhanced inflammatory response, decreased endothelial cell density, and increased ocular score and corneal thickness were observed, probably due to the influence of surface charge of copolymer membranes. On the other hand, the ionic pump function of corneal endothelium exposed to photopolymerized membranes was examined by analyzing the Na(+),K(+)-ATPase alpha 1 subunit (ATP1A1) expression level. The presence of the implants having higher amount of AAc incorporated in the copolymers (i.e., 15.1 to 24.7μmol) and zeta potential (i.e., -38.6 to -56.5mV) may lead to abnormal transmembrane transport. It is concluded that the chemical composition of HEMA/AAc has an important influence on the corneal tissue responses to polymeric biomaterials. © 2013.

Effects of Granulocyte-Macrophage Colony-Stimulating (GM-CSF) Factor on Corneal Epithelial Cells in Corneal Wound Healing Model

PubMed Central

Rho, Chang Rae; Park, Mi-young; Kang, Seungbum

2015-01-01

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that activates granulocyte and macrophage cell lineages. It is also known to have an important function in wound healing. This study investigated the effect of GM-CSF in wound healing of human corneal epithelial cells (HCECs). We used human GM-CSF derived from rice cells (rice cell-derived recombinant human GM-CSF; rhGM-CSF). An in vitro migration assay was performed to investigate the migration rate of HCECs treated with various concentrations of rhGM-CSF (0.1, 1.0, and 10.0 μg/ml). MTT assay and flow cytometric analysis were used to evaluate the proliferative effect of rhGM-CSF. The protein level of p38MAPK was analyzed by western blotting. For in vivo analysis, 100 golden Syrian hamsters were divided into four groups, and their corneas were de-epithelialized with alcohol and a blade. The experimental groups were treated with 10, 20, or 50 μg/ml rhGM-CSF four times daily, and the control group was treated with phosphate-buffered saline. The corneal wound-healing rate was evaluated by fluorescein staining at the initial wounding and 12, 24, 36, and 48 hours after epithelial debridement. rhGM-CSF accelerated corneal epithelial wound healing both in vitro and in vivo. MTT assay and flow cytometric analysis revealed that rhGM-CSF treatment had no effects on HCEC proliferation. Western blot analysis demonstrated that the expression level of phosphorylated p38MAPK increased with rhGM-CSF treatment. These findings indicate that rhGM-CSF enhances corneal wound healing by accelerating cell migration. PMID:26376304

Effect of chemical composition on corneal cellular response to photopolymerized materials comprising 2-hydroxyethyl methacrylate and acrylic acid.

PubMed

Lai, Jui-Yang

2013-10-01

Characterization of corneal cellular response to hydrogel materials is an important issue in ophthalmic applications. In this study, we aimed to investigate the relationship between the feed composition of 2-hydroxyethyl methacrylate (HEMA)/acrylic acid (AAc) and material compatibility towards corneal stromal and endothelial cells. The monomer solutions of HEMA and AAc were mixed at varying volume ratios of 92:0, 87:5, 82:10, 77:15, and 72:20, and were subjected to UV irradiation. Results of electrokinetic measurements showed that an increase in absolute zeta potential of photopolymerized membranes is observed with increasing the volume ratios of AAc/HEMA. Following 4 days of incubation with various hydrogels, the primary rabbit corneal stromal and endothelial cell cultures were examined for viability, proliferation, and pro-inflammatory gene expression. The samples prepared from the solution mixture containing 0-10 vol.% AAc displayed good cytocompatibility. However, with increasing volume ratio of AAc and HEMA from 15:77 to 20:72, the decreased viability, inhibited proliferation, and stimulated inflammation were noted in both cell types, probably due to the stronger charge-charge interactions. On the other hand, the ionic pump function of corneal endothelial cells exposed to photopolymerized membranes was examined by analyzing the Na(+),K(+)-ATPase alpha 1 subunit (ATP1A1) expression level. The presence of material samples having higher anionic charge density (i.e., zeta potential of -38 to -56 mV) may lead to abnormal transmembrane transport. It is concluded that the chemical composition of HEMA/AAc has an important influence on the corneal stromal and endothelial cell responses to polymeric biomaterials. Copyright © 2013 Elsevier B.V. All rights reserved.

Effects of Granulocyte-Macrophage Colony-Stimulating (GM-CSF) Factor on Corneal Epithelial Cells in Corneal Wound Healing Model.

PubMed

Rho, Chang Rae; Park, Mi-young; Kang, Seungbum

2015-01-01

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that activates granulocyte and macrophage cell lineages. It is also known to have an important function in wound healing. This study investigated the effect of GM-CSF in wound healing of human corneal epithelial cells (HCECs). We used human GM-CSF derived from rice cells (rice cell-derived recombinant human GM-CSF; rhGM-CSF). An in vitro migration assay was performed to investigate the migration rate of HCECs treated with various concentrations of rhGM-CSF (0.1, 1.0, and 10.0 μg/ml). MTT assay and flow cytometric analysis were used to evaluate the proliferative effect of rhGM-CSF. The protein level of p38MAPK was analyzed by western blotting. For in vivo analysis, 100 golden Syrian hamsters were divided into four groups, and their corneas were de-epithelialized with alcohol and a blade. The experimental groups were treated with 10, 20, or 50 μg/ml rhGM-CSF four times daily, and the control group was treated with phosphate-buffered saline. The corneal wound-healing rate was evaluated by fluorescein staining at the initial wounding and 12, 24, 36, and 48 hours after epithelial debridement. rhGM-CSF accelerated corneal epithelial wound healing both in vitro and in vivo. MTT assay and flow cytometric analysis revealed that rhGM-CSF treatment had no effects on HCEC proliferation. Western blot analysis demonstrated that the expression level of phosphorylated p38MAPK increased with rhGM-CSF treatment. These findings indicate that rhGM-CSF enhances corneal wound healing by accelerating cell migration.

Modified osteo-odonto-keratoprosthesis for treatment of corneal blindness: long-term anatomical and functional outcomes in 181 cases.

PubMed

Falcinelli, Giancarlo; Falsini, Benedetto; Taloni, Maurizio; Colliardo, Paolo; Falcinelli, Giovanni

2005-10-01

To evaluate long-term anatomical and functional outcomes of a modified osteo-odonto-keratoprosthesis (OOKP) technique for treatment of corneal blindness from various etiologies. Two-hundred three patients (224 eyes) underwent modified OOKP surgery between 1973 and 1999. Of the original cohort, 181 patients (98 men and 83 women; mean [SD], age 54.3 [15] years) in whom a standardized 2-step surgical procedure was performed were included in the study. Preoperative diagnoses were dry eye (n = 70) due to ocular pemphigoid (n = 39), Sjögren syndrome (n = 11), trachoma (n = 8), Lyell syndrome (n = 6), Stevens-Johnson syndrome (n = 4), and graft-vs-host disease (n = 1) and congenital lid coloboma (n = 1), severe corneal burns (n = 68), bullous keratopathy (n = 13), keratitis sequelae (n = 15), and bullous keratopathy secondary to antiglaucoma surgery (n = 15). Several innovations were made to the original Strampelli technique. Median follow-up duration was 12 years (range, 1-25 years). Anatomical complications leading to OOKP loss were found in 11 (6.07%) of 181 patients. Survival analysis estimated that 18 years after surgery, the probability of retaining an intact OOKP was 85% (95% confidence interval, 79.3%-90.7%). Pooling patient groups, mean (SD) best postoperative visual acuity was 0.76 (0.34). Mean (SD) final acuity at the end of follow-up declined slightly (0.69 [0.39]) but significantly (P<.01). In individual diagnostic groups, mean acuity decline reached statistical significance (P<.05) only in the pemphigoid (1 line), trachoma (1 line), and bullous keratopathy secondary to antiglaucoma surgery (2 lines) groups. Survival analysis estimated that 18 years after surgery, the probability of retaining best postoperative visual acuity (within 2 lines) was mean (SD) 55.5% (12.9%). Modified OOKP surgery for corneal blindness of different etiologies may provide, in the long-term, anatomically stable corneal prosthesis as well as an effective, rehabilitating recovery in visual acuity.

Posterior Corneal Characteristics of Cataract Patients with High Myopia

PubMed Central

Jing, Qinghe; Tang, Yating; Qian, Dongjin; Lu, Yi; Jiang, Yongxiang

2016-01-01

Purpose To evaluate the characteristics of the posterior corneal surface in patients with high myopia before cataract surgery. Methods We performed a cross-sectional study at the Eye and ENT Hospital of Fudan University, Shanghai, China. Corneal astigmatism and axial length were measured with a rotating Scheimpflug camera (Pentacam) and partial coherence interferometry (IOLMaster) in a high-myopia study group of 167 eyes (axial length ≥ 26 mm) and a control group of 150 eyes (axial length > 20 mm and < 25 mm). Results Total corneal astigmatism and anterior corneal astigmatism values were higher in the high-myopia group than in the control group. There was no significant difference in posterior corneal astigmatism between the high-myopia study group and the control group. In the study group, the mean posterior corneal astigmatism (range 0 – −0.9 diopters) was –0.29 diopters (D) ± 0.17 standard deviations (SD). The steep corneal meridian was aligned vertically (60°–120°) in 87.43% of eyes for the posterior corneal surface, and did not change with increasing age. There was a significant correlation (r = 0.235, p = 0.002) between posterior corneal astigmatism and anterior corneal astigmatism, especially when the anterior corneal surface showed with-the-rule (WTR) astigmatism (r = 0.452, p = 0.000). There was a weak negative correlation between posterior corneal astigmatism and age (r = –0.15, p = 0.053) in the high-myopia group. Compared with total corneal astigmatism values, the anterior corneal measurements alone overestimated WTR astigmatism by a mean of 0.27 ± 0.18 D in 68.75% of eyes, underestimated against-the-rule (ATR) astigmatism by a mean of 0.41 ± 0.28 D in 88.89% of eyes, and underestimated oblique astigmatism by a mean of 0.24 ± 0.13 D in 63.64% of eyes. Conclusions Posterior corneal astigmatism decreased with age and remained as ATR astigmatism in most cases of high myopia. There was a significant correlation between posterior corneal astigmatism and anterior corneal astigmatism when anterior corneal astigmatism was WTR. If posterior corneal astigmatism is not accounted for when selecting toric intraocular lenses for high-myopia patients, the use of anterior corneal astigmatism measurements alone will lead to overestimation of WTR astigmatism and underestimation of ATR and oblique astigmatism. PMID:27603713

Posterior Corneal Characteristics of Cataract Patients with High Myopia.

PubMed

Jing, Qinghe; Tang, Yating; Qian, Dongjin; Lu, Yi; Jiang, Yongxiang

2016-01-01

To evaluate the characteristics of the posterior corneal surface in patients with high myopia before cataract surgery. We performed a cross-sectional study at the Eye and ENT Hospital of Fudan University, Shanghai, China. Corneal astigmatism and axial length were measured with a rotating Scheimpflug camera (Pentacam) and partial coherence interferometry (IOLMaster) in a high-myopia study group of 167 eyes (axial length ≥ 26 mm) and a control group of 150 eyes (axial length > 20 mm and < 25 mm). Total corneal astigmatism and anterior corneal astigmatism values were higher in the high-myopia group than in the control group. There was no significant difference in posterior corneal astigmatism between the high-myopia study group and the control group. In the study group, the mean posterior corneal astigmatism (range 0 - -0.9 diopters) was -0.29 diopters (D) ± 0.17 standard deviations (SD). The steep corneal meridian was aligned vertically (60°-120°) in 87.43% of eyes for the posterior corneal surface, and did not change with increasing age. There was a significant correlation (r = 0.235, p = 0.002) between posterior corneal astigmatism and anterior corneal astigmatism, especially when the anterior corneal surface showed with-the-rule (WTR) astigmatism (r = 0.452, p = 0.000). There was a weak negative correlation between posterior corneal astigmatism and age (r = -0.15, p = 0.053) in the high-myopia group. Compared with total corneal astigmatism values, the anterior corneal measurements alone overestimated WTR astigmatism by a mean of 0.27 ± 0.18 D in 68.75% of eyes, underestimated against-the-rule (ATR) astigmatism by a mean of 0.41 ± 0.28 D in 88.89% of eyes, and underestimated oblique astigmatism by a mean of 0.24 ± 0.13 D in 63.64% of eyes. Posterior corneal astigmatism decreased with age and remained as ATR astigmatism in most cases of high myopia. There was a significant correlation between posterior corneal astigmatism and anterior corneal astigmatism when anterior corneal astigmatism was WTR. If posterior corneal astigmatism is not accounted for when selecting toric intraocular lenses for high-myopia patients, the use of anterior corneal astigmatism measurements alone will lead to overestimation of WTR astigmatism and underestimation of ATR and oblique astigmatism.

Assessment of corneal properties based on statistical modeling of OCT speckle.

PubMed

Jesus, Danilo A; Iskander, D Robert

2017-01-01

A new approach to assess the properties of the corneal micro-structure in vivo based on the statistical modeling of speckle obtained from Optical Coherence Tomography (OCT) is presented. A number of statistical models were proposed to fit the corneal speckle data obtained from OCT raw image. Short-term changes in corneal properties were studied by inducing corneal swelling whereas age-related changes were observed analyzing data of sixty-five subjects aged between twenty-four and seventy-three years. Generalized Gamma distribution has shown to be the best model, in terms of the Akaike's Information Criterion, to fit the OCT corneal speckle. Its parameters have shown statistically significant differences (Kruskal-Wallis, p < 0.001) for short and age-related corneal changes. In addition, it was observed that age-related changes influence the corneal biomechanical behaviour when corneal swelling is induced. This study shows that Generalized Gamma distribution can be utilized to modeling corneal speckle in OCT in vivo providing complementary quantified information where micro-structure of corneal tissue is of essence.

Measurement of Posterior Corneal Astigmatism by the IOLMaster 700.

PubMed

LaHood, Benjamin R; Goggin, Michael

2018-05-01

To provide the first description of posterior corneal astigmatism as measured by the IOLMaster 700 (Carl Zeiss Meditec, Jena, Germany) and assess how its characteristics compare to previous measurements from other devices. A total of 1,098 routine IOLMaster 700 biometric measurements were analyzed to provide magnitudes and orientation of steep and flat axes of anterior and posterior corneal astigmatism. Subgroup analysis was conducted to assess correlation of posterior corneal astigmatism characteristics to anterior corneal astigmatism and describe the distribution of posterior corneal astigmatism with age. Mean posterior corneal astigmatism was 0.24 ± 0.15 diopters (D). The steep axis of posterior corneal astigmatism was vertically oriented in 73.32% of measurements. Correlation between the magnitude of anterior and posterior corneal astigmatism was greatest when the steep axis of the anterior corneal astigmatism was oriented vertically (r = 0.68, P < .0001). Vertical orientation of the steep axis of anterior corneal astigmatism became less common as age increased, whereas for posterior corneal astigmatism it remained by far the most common orientation. This first description of posterior corneal astigmatism measurement by the IOLMaster 700 found the average magnitude of posterior corneal astigmatism and proportion of vertical orientation of steep axis was lower than previous estimates. The IOLMaster 700 appears capable of providing enhanced biometric measurement for individualized surgical planning. [J Refract Surg. 2018;34(5):331-336.]. Copyright 2018, SLACK Incorporated.

Topographical analysis of corneal astigmatism in patients with tilted-disc syndrome.

PubMed

Bozkurt, Banu; Irkec, Murat; Gedik, Sansal; Orhan, Mehmet; Erdener, Uğur

2002-07-01

To evaluate the corneal topography in patients with tilted-disc syndrome to determine the relationship between optic disc dysversion and corneal astigmatism and the pattern of astigmatism in these patients. The study included 23 eyes of the 13 tilted-disc syndrome patients with spheric refractive errors ranging between +1.00 D and -9.00 D (mean -4.00 +/- 3.4 D) and astigmatic errors ranging between -0.50 and -4.50 D (mean -1.95 +/- 0.93 D). Corneal topography was performed by computer-assisted videokeratoscope topographic modelling system 2 (TMS-2) and incidence of corneal astigmatism, corneal topographic patterns, and mean values of the topographic indices were determined. Corneal topographic analysis showed corneal astigmatism in 22 out of 23 patients with tilted discs. Corneal astigmatism was symmetric bow tie pattern in 10 eyes (45.45%), asymmetric bow tie pattern in 11 eyes (50%) and irregular in 1 eye (4.5%). Among the patients with bow tie pattern group (21 eyes), 14 eyes had with-the-rule astigmatism, 1 eye had against-the-rule astigmatism, and 6 eyes had oblique astigmatism. In 18 eyes, astigmatism was corneal, whereas combined corneal and lenticular in 4 eyes and lenticular in 1 eye. In the majority of tilted-disc cases, ocular astigmatism is mainly corneal. Morphogenetic factors in the development of the tilted disc might possibly influence the corneal development in such a way to result in corneal astigmatism.

Irregular Corneas: Improve Visual Function With Scleral Contact Lenses.

PubMed

de Luis Eguileor, Beatriz; Etxebarria Ecenarro, Jaime; Santamaria Carro, Alaitz; Feijoo Lera, Raquel

2018-05-01

To assess visual function in patients with irregular cornea who do not tolerate gas permeable (GP) corneal contact lenses and are fitted with GP scleral contact lenses (Rose K2 XL). In this prospective study, we analyzed 15 eyes of 15 patients who did not tolerate GP corneal contact lenses and were fitted with scleral contact lenses (Rose K2 XL). We assessed visual function using visual acuity and the visual function index (VF-14); we used the VF-14 as an indicator of patient satisfaction. The measurements were taken with the optical correction used before and 1 month after the fitting of the Rose K2 XL contact lenses. We also recorded the number of hours lenses had been worn over the first month. Using Rose K2 XL contact lenses, visual acuity was 0.06±0.07 logMAR. In all cases, visual acuity had improved compared with the measurement before fitting the lenses (0.31±0.18 logMAR; P=0.001). VF-14 scores were 72.74±12.38 before fitting of the scleral lenses, and 89.31±10.87 after 1 month of lens use (P=0.003). Patients used these scleral lenses for 9.33±2.99 comfortable hours of wear. Both visual acuity and VF-14 may improve after fitting Rose K2 XL contact lenses in patients with irregular corneas. In addition, in our patients, these lenses can be worn for a longer period than GP corneal contact lenses.

Rebamipide ophthalmic suspension for the treatment of dry eye syndrome: a critical appraisal

PubMed Central

Kashima, Tomoyuki; Itakura, Hirotaka; Akiyama, Hideo; Kishi, Shoji

2014-01-01

Rebamipide was initially developed and approved for use in treating gastric ulcers and lesions associated with gastritis. Discovery of its ability to increase gastric mucin led to investigations of its effect on ocular surface mucin and the subsequent development for use in dry eye patients. Investigations have confirmed that rebamipide increases corneal and conjunctival mucin-like substances along with improving corneal and conjunctival injury. Clinically, rebamipide ophthalmic suspensions can effectively treat tear deficiency and mucin-caused corneal epithelial damage, and can restore the microstructure responsible for tear stability. Topical rebamipide has also been shown to be effective in treating other ocular surface disorders such as lagophthalmos, lid wiper epitheliopathy, and persistent corneal erosion. Rebamipide’s ability to modify epithelial cell function, improve tear stability, and suppress inflammation in the absence of any known major side effects suggest that it may be a beneficial first drug of choice for severe dry eye treatment and other ocular surface disorders. This review summarizes the history and development of this innovative dry eye treatment from its initial use as an effective stomach medication to its current use in the treatment of dry eye in Japan. PMID:24940041

Autosomal-dominant Meesmann epithelial corneal dystrophy without an exon mutation in the keratin-3 or keratin-12 gene in a Chinese family.

PubMed

Cao, Wei; Yan, Ming; Hao, QianYun; Wang, ShuLin; Wu, LiHua; Liu, Qing; Li, MingYan; Biddle, Fred G; Wu, Wei

2013-04-01

Meesmann epithelial corneal dystrophy (MECD) is a dominantly inherited disorder, characterized by fragility of the anterior corneal epithelium and formation of intraepithelial microcysts. It has been described in a number of different ancestral groups. To date, all reported cases of MECD have been associated with either a single mutation in one exon of the keratin-3 gene (KRT3) or a single mutation in one of two exons of the keratin-12 gene (KRT12). Each mutation leads to a predicted amino acid change in the respective keratin-3 or keratin-12 proteins that combine to form the corneal-specific heterodimeric intermediate filament protein. This case report describes a four-generation Chinese kindred with typical autosomal-dominant MECD. Exon sequencing of KRT3 and KRT12 in six affected and eight unaffected individuals (including two spouses) did not detect any mutations or nucleotide sequence variants. This kindred demonstrates that single mis-sense mutations may be sufficient but are not required in all individuals with the MECD phenotype. It provides a unique opportunity to investigate further genomic and functional heterogeneity in MECD.

NGF protects corneal, retinal, and cutaneous tissues/cells from phototoxic effect of UV exposure.

PubMed

Rocco, Maria Luisa; Balzamino, Bijorn Omar; Aloe, Luigi; Micera, Alessandra

2018-04-01

Based on evidence that nerve growth factor (NGF) exerts healing action on damaged corneal, retinal, and cutaneous tissues, the present study sought to assess whether topical NGF application can prevent and/or protect epithelial cells from deleterious effects of ultraviolet (UV) radiation. Eyes from 40 young-adult Sprague Dawley rats and cutaneous tissues from 36 adult nude mice were exposed to UVA/B lamp for 60 min, either alone or in the presence of murine NGF. Corneal, retinal, and cutaneous tissues were sampled/processed for morphological, immunohistochemical, and biomolecular analysis, and results were compared statistically. UV exposure affected both biochemical and molecular expression of NGF and trkA NGFR in corneal, retinal, and cutaneous tissues while UV exposure coupled to NGF treatment enhanced NGF and trkA NGFR expression as well as reduced cell death. Overall, the findings of this in vivo/ex vivo study show the NGF ability to reduce the potential UV damage. Although the mechanism underneath this effect needs further investigation, these observations prospect the development of a pharmacological NGF-based therapy devoted to maintain cell function when exposed to phototoxic UV radiation.

Rebamipide ophthalmic suspension for the treatment of dry eye syndrome: a critical appraisal.

PubMed

Kashima, Tomoyuki; Itakura, Hirotaka; Akiyama, Hideo; Kishi, Shoji

2014-01-01

Rebamipide was initially developed and approved for use in treating gastric ulcers and lesions associated with gastritis. Discovery of its ability to increase gastric mucin led to investigations of its effect on ocular surface mucin and the subsequent development for use in dry eye patients. Investigations have confirmed that rebamipide increases corneal and conjunctival mucin-like substances along with improving corneal and conjunctival injury. Clinically, rebamipide ophthalmic suspensions can effectively treat tear deficiency and mucin-caused corneal epithelial damage, and can restore the microstructure responsible for tear stability. Topical rebamipide has also been shown to be effective in treating other ocular surface disorders such as lagophthalmos, lid wiper epitheliopathy, and persistent corneal erosion. Rebamipide's ability to modify epithelial cell function, improve tear stability, and suppress inflammation in the absence of any known major side effects suggest that it may be a beneficial first drug of choice for severe dry eye treatment and other ocular surface disorders. This review summarizes the history and development of this innovative dry eye treatment from its initial use as an effective stomach medication to its current use in the treatment of dry eye in Japan.

Hyperspectral Image Enhancement and Mixture Deep-Learning Classification of Corneal Epithelium Injuries

PubMed Central

Md Noor, Siti Salwa; Michael, Kaleena; Marshall, Stephen; Ren, Jinchang

2017-01-01

In our preliminary study, the reflectance signatures obtained from hyperspectral imaging (HSI) of normal and abnormal corneal epithelium tissues of porcine show similar morphology with subtle differences. Here we present image enhancement algorithms that can be used to improve the interpretability of data into clinically relevant information to facilitate diagnostics. A total of 25 corneal epithelium images without the application of eye staining were used. Three image feature extraction approaches were applied for image classification: (i) image feature classification from histogram using a support vector machine with a Gaussian radial basis function (SVM-GRBF); (ii) physical image feature classification using deep-learning Convolutional Neural Networks (CNNs) only; and (iii) the combined classification of CNNs and SVM-Linear. The performance results indicate that our chosen image features from the histogram and length-scale parameter were able to classify with up to 100% accuracy; particularly, at CNNs and CNNs-SVM, by employing 80% of the data sample for training and 20% for testing. Thus, in the assessment of corneal epithelium injuries, HSI has high potential as a method that could surpass current technologies regarding speed, objectivity, and reliability. PMID:29144388

[Biomaterials or Donor Tissue - What is the Future of Tissue Engenieering for Cornea Reconstruction?

PubMed

Bachmann, Björn O; Schrader, Stefan

2017-06-01

For the replacement of corneal tissue, corneal grafts or amniotic membrane are still used as a standard material. Since this is biological tissue, there is only a limited standardization regarding preparation, tissue properties and behaviour after transplantation. In addition, there is a risk of disease transmission, and the availability of both human corneas and amniotic membrane is insufficient in many regions of the world, which is why alternative biomaterials have been explored for many years now. Among the natural biomaterials, materials based on collagen or keratin provide characteristics that make them good candidates for corneal tissue replacement. However, there are still many unsolved problems, particularly regarding the degradation after implantation and the seam strength of the materials. Initial clinical studies with different biomaterials based on collagen prove their good biocompatibility to integrate and their low immunogenicity. Currently, there is no biomaterial that meets the requirements in every situation. It can be assumed that different biomaterials will be available in the future, which, depending on the underlying corneal disease, will fulfill different functions and thus make a patient- and disease-specific care possible. Georg Thieme Verlag KG Stuttgart · New York.

Topical Drug Formulations for Prolonged Corneal Anesthesia

PubMed Central

Wang, Liqiang; Shankarappa, Sahadev A.; Tong, Rong; Ciolino, Joseph B.; Tsui, Jonathan H.; Chiang, Homer H.; Kohane, Daniel S.

2013-01-01

Purpose Ocular local anesthetics (OLA’s) currently used in routine clinical practice for corneal anesthesia are short acting and their ability to delay corneal healing makes them unsuitable for long-term use. In this study, we examined the effect on the duration of corneal anesthesia of the site-1 sodium channel blocker tetrodotoxin (TTX), applied with either proparacaine or the chemical permeation enhancer OTAB. The effect of test solutions on corneal healing was also studied. Methods Solutions of TTX, proparacaine, and OTAB, singly or in combination were applied topically to the rat cornea. The blink response, an indirect measure of corneal sensitivity, was recorded using a Cochet-Bonnet esthesiometer, and the duration of corneal anesthesia calculated. The effect of test compounds on the rate of corneal epithelialization was studied in vivo following corneal debridement. Results Combination of TTX and proparacaine resulted in corneal anesthesia that was 8–10 times longer in duration than that from either drug administered alone, while OTAB did not prolong anesthesia. The rate of corneal healing was moderately delayed following co-administration of TTX and proparacaine. Conclusion Co-administration of TTX and proparacaine significantly prolonged corneal anesthesia but in view of delayed corneal re-epithelialization, caution is suggested in use of the combination. PMID:23615270

Cornea and anterior eye assessment with placido-disc keratoscopy, slit scanning evaluation topography and scheimpflug imaging tomography

PubMed Central

Martin, Raul

2018-01-01

Current corneal assessment technologies make the process of corneal evaluation extremely fast and simple and several devices and technologies allow to explore and to manage patients. The purpose of this special issue is to present and also to update in the evaluation of cornea and ocular surface and this second part, reviews a description of the corneal topography and tomography techniques, providing updated information of the clinical recommendations of these techniques in eye care practice. Placido-based topographers started an exciting anterior corneal surface analysis that allows the development of current corneal tomographers that provide a full three-dimensional reconstruction of the cornea including elevation, curvature, and pachymetry data of anterior and posterior corneal surfaces. Although, there is not an accepted reference standard technology for corneal topography description and it is not possible to determine which device produces the most accurate topographic measurements, placido-based topographers are a valuable technology to be used in primary eye care and corneal tomograhers expanding the possibilities to explore cornea and anterior eye facilitating diagnosis and follow-up in several situations, raising patient follow-up, and improving the knowledge regarding to the corneal anatomy. Main disadvantages of placido-based topographers include the absence of information about the posterior corneal surface and limited corneal surface coverage without data from the para-central and/or peripheral corneal surface. However, corneal tomographers show repeatable anterior and posterior corneal surfaces measurements, providing full corneal thickness data improving cornea, and anterior surface assessment. However, differences between devices suggest that they are not interchangeable in clinical practice. PMID:29480244

Cornea and anterior eye assessment with placido-disc keratoscopy, slit scanning evaluation topography and scheimpflug imaging tomography.

PubMed

Martin, Raul

2018-03-01

Current corneal assessment technologies make the process of corneal evaluation extremely fast and simple and several devices and technologies allow to explore and to manage patients. The purpose of this special issue is to present and also to update in the evaluation of cornea and ocular surface and this second part, reviews a description of the corneal topography and tomography techniques, providing updated information of the clinical recommendations of these techniques in eye care practice. Placido-based topographers started an exciting anterior corneal surface analysis that allows the development of current corneal tomographers that provide a full three-dimensional reconstruction of the cornea including elevation, curvature, and pachymetry data of anterior and posterior corneal surfaces. Although, there is not an accepted reference standard technology for corneal topography description and it is not possible to determine which device produces the most accurate topographic measurements, placido-based topographers are a valuable technology to be used in primary eye care and corneal tomograhers expanding the possibilities to explore cornea and anterior eye facilitating diagnosis and follow-up in several situations, raising patient follow-up, and improving the knowledge regarding to the corneal anatomy. Main disadvantages of placido-based topographers include the absence of information about the posterior corneal surface and limited corneal surface coverage without data from the para-central and/or peripheral corneal surface. However, corneal tomographers show repeatable anterior and posterior corneal surfaces measurements, providing full corneal thickness data improving cornea, and anterior surface assessment. However, differences between devices suggest that they are not interchangeable in clinical practice.

The characteristics of premature infants with transient corneal haze.

PubMed

Lai, Yu-Hung; Chen, Hsiu-Lin; Yang, San-Nan; Chang, Shun-Jen; Chuang, Lea-Yea; Wu, Wen-Chuan

2018-01-01

The etiology of transient corneal haze in premature infants is not known and how it relates to clinical outcomes in premature infants is not clear. To study associated factors of transient corneal haze in premature infants. We performed a retrospective study of 261 premature infants from retinopathy of prematurity (ROP) screening in the neonatal intensive care unit at a tertiary referral hospital. Characteristics of premature infants with and without corneal haze were analyzed by correlation tests, Chi-square tests, and logistic regressions were used for statistical analyses. Associations between corneal haze and birth weight (BW), gestational age at birth (GA), central corneal thickness, intraocular pressure, and other systemic and ophthalmic data were evaluated. The incidence of corneal haze was 13.4%. Lower BW, lower GA, packed red blood cells (RBC) transfusion, more days on oxygen, older maternal age, bronchopulmonary disease, and stage 3 ROP are associated with corneal haze. The severity of corneal haze decreased with infants' postmenstrual age. Multivariate logistic regression analyses revealed that BW and maternal age are the most important predictors of corneal haze. Low BW and older maternal age are the most important predictors of corneal haze in premature infants. Premature infants with corneal haze could carry more systemic and ocular morbidities. Hence they may require more clinical attention. Corneal haze is unlikely to hinder the treatment of ROP. However, it is possible that corneal haze could hinder the examination of ROP in some infants. If corneal haze does interfere with ROP screening, a closer, more conservative follow-up schedule with a senior ophthalmologist experienced in managing ROP is recommended.

Novel mutation in the CHST6 gene causes macular corneal dystrophy in a black South African family.

PubMed

Carstens, Nadia; Williams, Susan; Goolam, Saadiah; Carmichael, Trevor; Cheung, Ming Sin; Büchmann-Møller, Stine; Sultan, Marc; Staedtler, Frank; Zou, Chao; Swart, Peter; Rice, Dennis S; Lacoste, Arnaud; Paes, Kim; Ramsay, Michèle

2016-07-20

Macular corneal dystrophy (MCD) is a rare autosomal recessive disorder that is characterized by progressive corneal opacity that starts in early childhood and ultimately progresses to blindness in early adulthood. The aim of this study was to identify the cause of MCD in a black South African family with two affected sisters. A multigenerational South African Sotho-speaking family with type I MCD was studied using whole exome sequencing. Variant filtering to identify the MCD-causal mutation included the disease inheritance pattern, variant minor allele frequency and potential functional impact. Ophthalmologic evaluation of the cases revealed a typical MCD phenotype and none of the other family members were affected. An average of 127 713 variants per individual was identified following exome sequencing and approximately 1.2 % were not present in any of the investigated public databases. Variant filtering identified a homozygous E71Q mutation in CHST6, a known MCD-causing gene encoding corneal N-acetyl glucosamine-6-O-sulfotransferase. This E71Q mutation results in a non-conservative amino acid change in a highly conserved functional domain of the human CHST6 that is essential for enzyme activity. We identified a novel E71Q mutation in CHST6 as the MCD-causal mutation in a black South African family with type I MCD. This is the first description of MCD in a black Sub-Saharan African family and therefore contributes valuable insights into the genetic aetiology of this disease, while improving genetic counselling for this and potentially other MCD families.

Comparison of in vivo efficacy of different ocular lubricants in dry eye animal models.

PubMed

Zheng, Xiaodong; Goto, Tomoko; Ohashi, Yuichi

2014-04-29

To compare the efficacy of three types of ocular lubricants in protecting corneal epithelial cells in dry eye animal models. Ocular lubricants containing 0.1% or 0.3% sodium hyaluronate (SH), carboxymethylcellulose (CMC), or hydroxypropyl methylcellulose (HPMC) were tested. First, ocular lubricant containing 0.002% fluorescein was dropped onto the rabbit corneas. The fluorescein intensity as an index of retention was measured. Second, a rabbit dry eye model was made by holding the eye open with a speculum, and 50 μL of each ocular lubricant was dropped onto the cornea. After 3 hours, the corneas were stained with 1% methylene blue (MB), and the absorbance of MB was measured. Third, a rat dry eye model was treated with the ocular lubricants for 4 weeks, and the corneal fluorescein staining was scored. Eyes treated with physiological saline were used as controls. Finally, immunohistochemistry was used to analyze occludin, an epithelial barrier protein, in cultured human corneal epithelial cells pretreated with ocular lubricants and desiccated for 20 or 60 minutes. Our results showed that 0.3% SH had a significantly longer retention time than the other lubricants (all P < 0.01). The absorbance of MB was significantly lower in the 0.3% SH group. The corneas of rats exposed to 0.3% SH had significantly lower fluorescein staining scores. A significantly higher number of occludin-positive cells were found after exposure to 0.3% SH than other lubricants. Ocular lubricant containing 0.3% SH would be preferable to treat patients with dry eye syndrome. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Lipopolysaccharide precipitates hepatic encephalopathy and increases blood-brain barrier permeability in mice with acute liver failure.

PubMed

Chastre, Anne; Bélanger, Mireille; Nguyen, Bich N; Butterworth, Roger F

2014-03-01

Acute liver failure (ALF) is frequently complicated by infection leading to precipitation of central nervous system complications such as hepatic encephalopathy (HE) and increased mortality. There is evidence to suggest that when infection occurs in ALF patients, the resulting pro-inflammatory mechanisms may be amplified that could, in turn, have a major impact on blood-brain barrier (BBB) function. The aim of this study was to investigate the role of endotoxemia on the progression of encephalopathy in relation to BBB permeability during ALF. Adult male C57-BL6 mice with ALF resulting from azoxymethane-induced toxic liver injury were administered trace amounts of the endotoxin component lipopolysaccharide (LPS). Effects on the magnitude of the systemic inflammatory response, liver pathology and BBB integrity were measured as a function of progression of HE, defined as time to loss of corneal reflex (coma). Lipopolysaccharide caused additional two- to seven-fold (P < 0.001) increases in circulating pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), worsening liver pathology and associated increases of circulating transaminases as well as increased hyperammonaemia consistent with a further loss of viable hepatocytes. LPS treatment of ALF mice led to a rapid precipitation of hepatic coma and the BBB became permeable to the 25-kDa protein immunoglobulin G (IgG). This extravasation of IgG was accompanied by ignificant up-regulation of matrix metalloproteinase-9 (MMP-9), an endopeptidase known to modulate opening of the BBB in a wide range of neurological disorders. These findings represent the first direct evidence of inflammation-related BBB permeability changes in ALF. © 2013 John Wiley & Sons A/S. Publishing by John Wiley & Sons Ltd.

Study of light scattering and transparency in human edematous corneas and application to corneal grafts

NASA Astrophysics Data System (ADS)

Marciano, Tal; Peyrot, Donald; Crotti, Caroline; Alahyane, Fatima; Kowalczuk, Laura; Plamann, Karsten

2011-07-01

The optical properties of the cornea have been a research subject of great interest for many years. Several early theories have been put forward to explain with more or less success the optical transparency of this tissue, but it was not until Maurice demonstrated in a very elegant way during the 50s that this optical transparency could be explained by the regular ultrastructure of the cornea. When becoming edematous, the cornea's ultrastructure is perturbed and the tissue becomes a strongly scattering medium. With the emergence of ophthalmologic surgery by ultrashort pulse lasers in recent years, a regain of interest in the subject of corneal transparency arose. However, relatively little and no recent data of transparency spectra measurements covering a large wavelength range is available in the literature. The purpose of this study is to provide quantitative values for light scattering and its relation to the degree of edema by measuring the spectrum of transmitted light through corneas presenting different degrees of edema. This paper focus on the comparison of laboratory measurements published earlier with a new simple method we propose We also for eye banks to quantitatively measure the degree of transparency of corneal grafts by measuring the modulation transfer function of a Siemens star viewed through a corneal graft. Indeed, there is no current method to determine the transparency of corneal graft but the subjectivity of the laboratory technician or the ophthalmic surgeon.

Tuna cornea as biomaterial for cardiac applications.

PubMed

Parravicini, Roberto; Cocconcelli, Flavio; Verona, Alessandro; Parravicini, Valeriano; Giuliani, Enrico; Barbieri, Alberto

2012-01-01

Among available biomaterials, cornea is almost completely devoid of cells and is composed only of collagen fibers oriented in an orderly pattern, which contributes to low antigenicity. Thunnus thynnus, the Atlantic bluefin tuna, is a fish with large eyes that can withstand pressures of approximately 10 MPa. We evaluated the potential of this tuna cornea in cardiac bioimplantation. Eyes from freshly caught Atlantic bluefin tuna were harvested and preserved in a fixative solution. Sterilized samples of corneal stroma were embedded in paraffin and stained with hematoxylin and eosin, and the histologic features were studied. Physical and mechanical resistance tests were performed in comparison with bovine pericardial strips and porcine mitral valves. Corneal material was implanted subcutaneously in 7 rats, to evaluate in vivo calcification rates. Mitral valves made from tuna corneal leaflets were implanted in 9 sheep. We found that the corneal tissue consisted only of parallel collagen fibers without evidence of vascular or neural structures. In tensile strength, the tuna corneal specimens were substantially similar to bovine pericardium. After 23 days, the rat-implanted samples showed no calcium or calcium salt deposition. Hydrodynamic and fatigue testing of valve prototypes yielded acceptable functional and long-term behavioral results. In the sheep, valvular performance was stable during the 180-day follow-up period, with no instrumental sign of calcification at the end of observation. We conclude that low antigenicity and favorable physical properties qualify tuna cornea as a potential material for durable bioimplantation. Further study is warranted.

Mitochondrial transfer of mesenchymal stem cells effectively protects corneal epithelial cells from mitochondrial damage.

PubMed

Jiang, Dan; Gao, Fei; Zhang, Yuelin; Wong, David Sai Hung; Li, Qing; Tse, Hung-Fat; Xu, Goufeng; Yu, Zhendong; Lian, Qizhou

2016-11-10

Recent studies have demonstrated that mesenchymal stem cells (MSCs) can donate mitochondria to airway epithelial cells and rescue mitochondrial damage in lung injury. We sought to determine whether MSCs could donate mitochondria and protect against oxidative stress-induced mitochondrial dysfunction in the cornea. Co-culturing of MSCs and corneal epithelial cells (CECs) indicated that the efficiency of mitochondrial transfer from MSCs to CECs was enhanced by Rotenone (Rot)-induced oxidative stress. The efficient mitochondrial transfer was associated with increased formation of tunneling nanotubes (TNTs) between MSCs and CECs, tubular connections that allowed direct intercellular communication. Separation of MSCs and CECs by a transwell culture system revealed no mitochiondrial transfer from MSCs to CECs and mitochondrial function was impaired when CECs were exposed to Rot challenge. CECs with or without mitochondrial transfer from MSCs displayed a distinct survival capacity and mitochondrial oxygen consumption rate. Mechanistically, increased filopodia outgrowth in CECs for TNT formation was associated with oxidative inflammation-activated NFκB/TNFαip2 signaling pathways that could be attenuated by reactive oxygen species scavenger N-acetylcysteine (NAC) treatment. Furthermore, MSCs grown on a decellularized porcine corneal scaffold were transplanted onto an alkali-injured eye in a rabbit model. Enhanced corneal wound healing was evident following healthy MSC scaffold transplantation. And transferred mitochondria was detected in corneal epithelium. In conclusion, mitochondrial transfer from MSCs provides novel protection for the cornea against oxidative stress-induced mitochondrial damage. This therapeutic strategy may prove relevant for a broad range of mitochondrial diseases.

Severing corneal nerves in one eye induces sympathetic loss of immune privilege and promotes rejection of future corneal allografts placed in either eye

PubMed Central

Paunicka, Kathryn J.; Mellon, Jessamee; Robertson, Danielle; Petroll, Matthew; Brown, Joseph R.; Niederkorn, Jerry Y.

2015-01-01

Less than 10% of corneal allografts undergo rejection even though HLA matching is not performed. However, second corneal transplants experience a three-fold increase in rejection, which is not due to prior sensitization to histocompatibility antigens shared by the first and second transplants since corneal grafts are selected at random without histocompatibility matching. Using a mouse model of penetrating keratoplasty we found that 50% of the initial corneal transplants survived, yet 100% of the subsequent corneal allografts (unrelated to the first graft) placed in the opposite eye underwent rejection. The severing of corneal nerves that occurs during surgery induced substance P (SP) secretion in both eyes, which disabled T regulatory cells that are required for allograft survival. Administration of an SP antagonist restored immune privilege and promoted graft survival. Thus, corneal surgery produces a sympathetic response that permanently abolishes immune privilege of subsequent corneal allografts, even those placed in the opposite eye and expressing a completely different array of foreign histocompatibility antigens from the first corneal graft. PMID:25872977

Assessment of corneal properties based on statistical modeling of OCT speckle

PubMed Central

Jesus, Danilo A.; Iskander, D. Robert

2016-01-01

A new approach to assess the properties of the corneal micro-structure in vivo based on the statistical modeling of speckle obtained from Optical Coherence Tomography (OCT) is presented. A number of statistical models were proposed to fit the corneal speckle data obtained from OCT raw image. Short-term changes in corneal properties were studied by inducing corneal swelling whereas age-related changes were observed analyzing data of sixty-five subjects aged between twenty-four and seventy-three years. Generalized Gamma distribution has shown to be the best model, in terms of the Akaike’s Information Criterion, to fit the OCT corneal speckle. Its parameters have shown statistically significant differences (Kruskal-Wallis, p < 0.001) for short and age-related corneal changes. In addition, it was observed that age-related changes influence the corneal biomechanical behaviour when corneal swelling is induced. This study shows that Generalized Gamma distribution can be utilized to modeling corneal speckle in OCT in vivo providing complementary quantified information where micro-structure of corneal tissue is of essence. PMID:28101409

Scheimpflug imaged corneal changes on anterior and posterior surfaces after collagen cross-linking

PubMed Central

Hassan, Ziad; Modis, Laszlo; Szalai, Eszter; Berta, Andras; Nemeth, Gabor

2014-01-01

AIM To compare the anterior and posterior corneal parameters before and after collagen cross-linking therapy for keratoconus. METHODS Collagen cross-linking was performed in 31 eyes of 31 keratoconus patients (mean age 30.6±8.9y). Prior to treatment and an average 7mo after therapy, Scheimpflug analysis was performed using Pentacam HR. In addition to corneal thickness assessments, corneal radius, elevation, and aberrometric measurements were performed both on anterior and posterior corneal surfaces. Data obtained before and after surgery were statistically analyzed. RESULTS In terms of horizontal and vertical corneal radius, and central corneal thickness no deviations were observed an average 7mo after operation. Corneal higher order aberration showed no difference neither on anterior nor on posterior corneal surfaces. During follow-up period, no significant deviation was detected regarding elevation values obtained by measurement in mm units between the 3.0-8.0 mm-zones. CONCLUSION Corneal stabilization could be observed in terms of anterior and posterior corneal surfaces, elevation and higher order aberration values 7mo after collagen cross-linking therapy for keratoconus. PMID:24790876

Age Differences in Axial Length, Corneal Curvature, and Corneal Astigmatism in Marfan Syndrome with Ectopia Lentis

PubMed Central

Jing, Qinghe; Tang, Yating; Qian, Dongjin

2018-01-01

Purpose To investigate the differences in axial length, corneal curvature, and corneal astigmatism with age in patients with Marfan syndrome (MFS) and ectopia lentis. Methods A retrospective case series study was conducted. MFS patients with ectopia lentis were divided into groups according to age. Axial length, corneal curvature, and corneal astigmatism were measured. Results This study included 114 MFS patients (215 eyes) with a mean age of 19.0 ± 13.9 years. Axial length differed significantly across age groups in MFS patients (P < 0.001), whereas corneal curvature did not (P = 0.767). Corneal astigmatism was statistically significant throughout the MFS cohort (P = 0.009), but no significant difference was found in young MFS patients (P = 0.838). With increasing age, the orientation of the corneal astigmatism changed from with-the-rule astigmatism to against-the-rule or oblique astigmatism (P < 0.001). A linear correlation analysis showed weak correlations between age and axial length for both eyes and with corneal astigmatism for the left eye, but there was no correlation between age and corneal curvature. Conclusions In MFS, axial length varies with age, corneal curvature remains stable, and corneal astigmatism is higher in young patients and tends to shift toward against-the-rule or oblique astigmatism. Therefore, it is important to consider age when diagnosing MFS with ocular biometric data. PMID:29854424

Corneal fibrosarcoma in a cat.

PubMed

Strong, Travis D; Tangeman, Sarah; Ben-Shlomo, Gil; Haynes, Joseph; Allbaugh, Rachel A

2016-07-01

To present the clinicopathologic features of a Domestic Short-haired cat with spontaneous, intermediate-grade corneal fibrosarcoma, possibly secondary to chronic corneal irritation associated with a corneal sequestrum. A 12-year-old, spayed female Domestic Short-haired cat was evaluated for a slowly growing, pink, exophytic mass affecting the left cornea. The cat had presented 6 years previously for bilateral brown corneal sequestra, as well as 3 years previously for a small pale growth on the left cornea hypothesized to be an epithelial inclusion cyst and a corneal ulcer affecting the right eye. Incisional biopsy of the corneal mass indicated intermediate-grade corneal fibrosarcoma within the corneal stroma. Owing to the potential for malignant behavior, the left globe was enucleated. Routine systemic staging was performed prior to surgery with no evidence of metastasis. Definitive diagnosis of corneal fibrosarcoma was made through histopathologic examination of the incisional biopsy. There was an elevated mitotic index, indicating an intermediate-grade phenotype. Histopathology of the enucleated globe substantiated the initial findings, and complete tumor resection was confirmed. Subjacent to the corneal fibrosarcoma, there was a region of necrotic tissue suggestive of a corneal sequestrum. Six months after diagnosis and enucleation, the patient remained healthy with no signs of local spread or distant metastasis. To the authors' knowledge, this is the first documented case of a corneal fibrosarcoma in a cat. © 2016 American College of Veterinary Ophthalmologists.

Corneal protection by the ocular mucin secretagogue 15(S)-HETE in a rabbit model of desiccation-induced corneal defect.

PubMed

Gamache, Daniel A; Wei, Zhong-You; Weimer, Lori K; Miller, Steven T; Spellman, Joan M; Yanni, John M

2002-08-01

The mucin secretagogue 15(S)-HETE was found to stimulate glycoprotein secretion in human ocular tissue at submicromolar concentrations in the present studies. Therefore, the ability of topically applied 15(S)-HETE to preserve corneal integrity was investigated in a rabbit model of desiccation-induced corneal defect. Desiccation-induced corneal injury was elicited in anesthetized rabbits by maintaining one eye open with a speculum. Corneal staining and corneal thickness changes were determined immediately following desiccation. 15(S)-HETE dose-dependently reduced corneal damage (ED50 = 120 nM) during a two-hour desiccation. Corneal staining was unchanged relative to control using a 1 microM dose of 15(S)-HETE. Through four hours of desiccation, 15(S)-HETE (500 nM) decreased corneal staining by 71% and completely prevented corneal thinning. 15(S)-HETE (1 microM) was significantly more efficacious than an artificial tear product over the 4-hour desiccation period. There was no evidence of tachyphylaxis following repeated topical ocular dosing of 15(S)-HETE. These studies demonstrate that 15(S)-HETE stimulates ocular mucin secretion in vitro and effectively protects the cornea in a rabbit model of desiccation-induced injury. The results suggest that the ocular mucin secretagogue 15(S)-HETE may have therapeutic utility in dry eye patients, alleviating corneal injury and restoring corneal integrity.

CO2 stimulation of the cornea: a comparison between human sensation and nerve activity in polymodal nociceptive afferents of the cat.

PubMed

Chen, X; Gallar, J; Pozo, M A; Baeza, M; Belmonte, C

1995-06-01

Excitation of nociceptors by low pH has been proposed as a cause of pain following tissue injury. Here we have studied the effect of pH reductions caused by application of CO2 pulses to the cornea on the activity of corneal afferent nerves of the cat and on the magnitude of pain sensations in humans. Single-unit activity was recorded from corneal afferent fibres in anaesthetized cats. The corneal receptive field of A-delta or C polymodal nociceptive units was exposed for 30 s to a gas mixture with different concentrations of CO2 in air (0, 35, 50, 65, 80 and 98.5%). Responses to CO2 were evoked at a mean threshold concentration of 40 +/- 3% CO2. They consisted of a discharge of impulses that decayed gradually to a tonic level. In 15% of the units the initial burst was absent. The CO2 concentration and firing frequency data could be fitted to a power function with an exponent of 1.12. Pulses of CO2 were also applied to the cornea of 16 human volunteers. Sensations experienced were measured by means of a visual analogue scale and a verbal descriptor scale. Flow was adjusted below the mechanical stimulation threshold (2.8 +/- 0.5 mg). When mixtures containing 10-90% CO2 in 5% steps were applied as 3 s pulses, threshold sensation, described as a mild stinging pain, was evoked at 33.5 +/- 4.0% CO2. This sensation became overtly painful with higher CO2 concentrations (47.5 +/- 3.6% CO2). For the same subject the sensory threshold was remarkably constant, though it changed with longer exposure times. The relationship between CO2 concentration and magnitude of pain could be adjusted to a power function with a power exponent of 1.12. Curves of CO2 concentration versus neural discharges in the cat and versus psychophysical sensation in humans were very similar. These results show that corneal polymodal nociceptors respond to protons, and encode changes in CO2 concentration presumably reflecting pH changes. The same stimulus evokes corneal pain sensations in humans, thus opening the possibility of using CO2 as an effective stimulus for corneal aesthesiometry.

Assessment of refractive astigmatism and simulated therapeutic refractive surgery strategies in coma-like-aberrations-dominant corneal optics.

PubMed

Zhou, Wen; Stojanovic, Aleksandar; Utheim, Tor Paaske

2016-01-01

The aim of the study is to raise the awareness of the influence of coma-like higher-order aberrations (HOAs) on power and orientation of refractive astigmatism (RA) and to explore how to account for that influence in the planning of topography-guided refractive surgery in eyes with coma-like-aberrations-dominant corneal optics. Eleven eyes with coma-like-aberrations-dominant corneal optics and with low lenticular astigmatism (LA) were selected for astigmatism analysis and for treatment simulations with topography-guided custom ablation. Vector analysis was used to evaluate the contribution of coma-like corneal HOAs to RA. Two different strategies were used for simulated treatments aiming to regularize irregular corneal optics: With both strategies correction of anterior corneal surface irregularities (corneal HOAs) were intended. Correction of total corneal astigmatism (TCA) and RA was intended as well with strategies 1 and 2, respectively. Axis of discrepant astigmatism (RA minus TCA minus LA) correlated strongly with axis of coma. Vertical coma influenced RA by canceling the effect of the with-the-rule astigmatism and increasing the effect of the against-the-rule astigmatism. After simulated correction of anterior corneal HOAs along with TCA and RA (strategies 1 and 2), only a small amount of anterior corneal astigmatism (ACA) and no TCA remained after strategy 1, while considerable amount of ACA and TCA remained after strategy 2. Coma-like corneal aberrations seem to contribute a considerable astigmatic component to RA in eyes with coma-like-aberrations dominant corneal optics. If topography-guided ablation is programmed to correct the corneal HOAs and RA, the astigmatic component caused by the coma-like corneal HOAs will be treated twice and will result in induced astigmatism. Disregarding RA and treating TCA along with the corneal HOAs is recommended instead.

A brief history of corneal transplantation: From ancient to modern.

PubMed

Crawford, Alexandra Z; Patel, Dipika V; McGhee, Charles Nj

2013-09-01

This review highlights many of the fundamental concepts and events in the development of corneal transplantation - from ancient times to modern. Tales of eye, limb, and even heart transplantation appear in ancient and medieval texts; however, in the scientific sense, the original concepts of corneal surgery date back to the Greek physician Galen (130-200 AD). Although proposals to provide improved corneal clarity by surgical interventions, including keratoprostheses, were better developed by the 17(th) and 18(th) centuries, true scientific and surgical experimentation in this field did not begin until the 19(th) century. Indeed, the success of contemporary corneal transplantation is largely the result of a culmination of pivotal ideas, experimentation, and perseverance by inspired individuals over the last 200 years. Franz Reisinger initiated experimental animal corneal transplantation in 1818, coining the term "keratoplasty". Subsequently, Wilhelmus Thorne created the term corneal transplant and 3 years later Samuel Bigger, 1837, reported successful corneal transplantation in a gazelle. The first recorded therapeutic corneal xenograft on a human was reported shortly thereafter in 1838-unsurprisingly this was unsuccessful. Further progress in corneal transplantation was significantly hindered by limited understanding of antiseptic principles, anesthesiology, surgical technique, and immunology. There ensued an extremely prolonged period of debate and experimentation upon the utility of animal compared to human tissue, and lamellar versus penetrating keratoplasty. Indeed, the first successful human corneal transplant was not performed by Eduard Zirm until 1905. Since that first successful corneal transplant, innumerable ophthalmologists have contributed to the development and refinement of corneal transplantation aided by the development of surgical microscopes, refined suture materials, the development of eye banks, and the introduction of corticosteroids. Recent developments, including the replacement of selected corneal layers rather than full-thickness keratoplasty, have the potential to improve or transform corneal transplant surgery in the future.

Novel aspects of corneal angiogenic and lymphangiogenic privilege

PubMed Central

Ellenberg, David; Azar, Dimitri T.; Hallak, Joelle A.; Tobaigy, Faisal; Han, Kyu Yeon; Jain, Sandeep; Zhou, Zhongjun; Chang, Jin-Hong

2013-01-01

In this article, we provide the results of experimental studies demonstrating that corneal avascularity is an active process involving the production of anti-angiogenic factors, which counterbalance the proangiogenic/lymphangiogenic factors that are upregulated during wound healing. We also summarize pertinent published reports regarding corneal neovascularization (NV), corneal lymphangiogenesis and corneal angiogenic/lymphangiogenic privilege. We outline the clinical causes of corneal NV, and discuss the angiogenic proteins (VEGF and bFGF) and angiogenesis regulatory proteins. We also describe the role of matrix metalloproteinases MMP-2, -7, and MT1-MMP, anti-angiogenic factors, and lymphangiogenic regulatory proteins during corneal wound healing. Established and potential new therapies for the treatment of corneal neovascularization are also discussed. PMID:20100589

Analysis of corneal topography in patients with pure microphthalmia in Eastern China.

PubMed

Hu, Pei-Hong; Gao, Gui-Ping; Yu, Yao; Pei, Chong-Gang; Zhou, Qiong; Huang, Xin; Zhang, Ying; Shao, Yi

2015-12-01

To determine the typical corneal changes in pure microphthalmia using a corneal topography system and identify characteristics that may assist in early diagnosis. Patients with pure microphthalmia and healthy control subjects underwent corneal topography analysis (Orbscan IIZ® Corneal Topography System; Bausch and Lomb, Bridgewater, NJ, USA) to determine degree of corneal astigmatism (mean A), simulation of corneal astigmatism (sim A), mean keratometry (mean K), simulated keratometry (sim K), irregularities in the 3 - and 5-mm zone, and mean thickness of nine distinct corneal regions. Patients with pure microphthalmia (n = 12) had significantly higher mean K, sim K, mean A, sim A, 3.0 mm irregularity and 5.0 mm irregularity, and exhibited significantly more false keratoconus than controls (n = 12). There was a significant between-group difference in the morphology of the anterior corneal surface and the central curvature of the cornea. Changes in corneal morphology observed in this study could be useful in borderline situations to confirm the diagnosis of pure microphthalmia. © The Author(s) 2015.

Corneal confocal microscopy detects small fiber neuropathy in CMT1A patients

PubMed Central

Tavakoli, Mitra; Marshall, Andy; Banka, Siddharth; Petropoulos, Ioannis N; Fadavi, Hassan; Kingston, Helen; Malik, Rayaz A

2012-01-01

Although unmyelinated nerve fibers are affected in CMT1A, they have not been studied in detail due to the invasive nature of the techniques needed to study them. We established alterations in C-fiber bundles of the cornea in patients with CMT1A using non-invasive corneal confocal microscopy (CCM). Twelve patients with CMT1A and twelve healthy control subjects underwent assessment of neuropathic symptoms and deficits, electrophysiology, quantitative sensory testing, corneal sensitivity and corneal confocal microscopy. Corneal sensitivity, corneal nerve fiber density, corneal nerve branch density, corneal nerve fiber length and corneal nerve fiber tortuosity were significantly reduced in CMT1A patients compared to controls. There was a significant correlation between corneal sensation and CCM parameters with the severity of painful neuropathic symptoms, cold and warm thresholds and median nerve CMAP amplitude. CCM demonstrates significant damage to C-fiber bundles, which relates to some measures of neuropathy in CMT1A patients. PMID:22996176

[Recurrent Corneal Erosions in Epithelial Corneal Dystrophies].

PubMed

Geerling, Gerd; Lisch, Walter; Finis, David

2018-06-01

The corneal epithelium is the most important structure of the ocular optical system. Recurrent corneal erosions can result from inflammation, trauma, degeneration and dystrophies. Epithelial basement membrane dystrophy (EBMD), epithelial recurrent erosion dystrophy (ERED) and Francheschetti and Meesmann's epithelial corneal dystrophy (MECD) can all - besides other signs and symptoms - result in more or less frequent corneal erosions. The pathomechanisms involved however are different. In EBMD, corneal erosions are facultative and clinical signs are often subtle. Aberrant basement membrane structures are associated with thinning of the epithelium and can be clinically identified as maps or fingerprints. In ERED, recurrent corneal erosions are - predominantly in the first decades of life - always present. A defect in the COL17A1 gene results in a dysfunctional hemidesmosome. In MECD, punctate corneal erosions are less frequent and result from intraepithelial microcysts which open spontaneously onto the ocular surface. Usually lubricants, therapeutic contact lenses and sometimes epithelial debridement and phototherapeutic keratectomy are the mainstay for treating corneal erosions in these three dystrophies. Georg Thieme Verlag KG Stuttgart · New York.

Corneal Toxicity Following Exposure to Asclepias Tuberosa

PubMed Central

Mikkelsen, Lauge Hjorth; Hamoudi, Hassan; Gül, Cigdem Altuntas; Heegaard, Steffen

2017-01-01

Purpose: To present a case of corneal toxicity following exposure to milky plant latex from Asclepias tuberosa. Methods: A 70-year-old female presented with blurred vision and pain in her left eye after handling an Ascepias tuberosa. Clinical examination revealed a corneal stromal oedema with small epithelial defects. The corneal endothelium was intact and folds in Descemets membrane were observed. The oedema was treated with chloramphenicol, dexamethasone and scopolamine. Results: The corneal oedema had appeared after corneal exposure to the plant, Asclepias tuberosa, whose latex contains cardenolides that inhibit the Na+/ K+-ATPase in the corneal endothelium. The oedema resolved after 96 hours. After nine months the best corrected visual acuity was 20/20. Conclusion: Corneal toxicity has previously been reported for plants of the Asclepias family. This is a rare case describing severe corneal toxicity caused by exposure to latex from Asclepias tuberosa. Handling of plants of the Asclepias family should be kept as a differential diagnosis in cases of acute corneal toxicity. PMID:28400886

Corneal Toxicity Following Exposure to Asclepias Tuberosa.

PubMed

Mikkelsen, Lauge Hjorth; Hamoudi, Hassan; Gül, Cigdem Altuntas; Heegaard, Steffen

2017-01-01

To present a case of corneal toxicity following exposure to milky plant latex from Asclepias tuberosa. A 70-year-old female presented with blurred vision and pain in her left eye after handling an Ascepias tuberosa . Clinical examination revealed a corneal stromal oedema with small epithelial defects. The corneal endothelium was intact and folds in Descemets membrane were observed. The oedema was treated with chloramphenicol, dexamethasone and scopolamine. The corneal oedema had appeared after corneal exposure to the plant, Asclepias tuberosa , whose latex contains cardenolides that inhibit the Na + / K + -ATPase in the corneal endothelium. The oedema resolved after 96 hours. After nine months the best corrected visual acuity was 20/20. Corneal toxicity has previously been reported for plants of the Asclepias family. This is a rare case describing severe corneal toxicity caused by exposure to latex from Asclepias tuberosa . Handling of plants of the Asclepias family should be kept as a differential diagnosis in cases of acute corneal toxicity.

Anterior Corneal, Posterior Corneal, and Lenticular Contributions to Ocular Aberrations.

PubMed

Atchison, David A; Suheimat, Marwan; Mathur, Ankit; Lister, Lucas J; Rozema, Jos

2016-10-01

To determine the corneal surfaces and lens contributions to ocular aberrations. There were 61 healthy participants with ages ranging from 20 to 55 years and refractions -8.25 diopters (D) to +3.25 D. Anterior and posterior corneal topographies were obtained with an Oculus Pentacam, and ocular aberrations were obtained with an iTrace aberrometer. Raytracing through models of corneas provided total corneal and surface component aberrations for 5-mm-diameter pupils. Lenticular contributions were given as differences between ocular and corneal aberrations. Theoretical raytracing investigated influence of object distance on aberrations. Apart from defocus, the highest aberration coefficients were horizontal astigmatism, horizontal coma, and spherical aberration. Most correlations between lenticular and ocular parameters were positive and significant, with compensation of total corneal aberrations by lenticular aberrations for 5/12 coefficients. Anterior corneal aberrations were approximately three times higher than posterior corneal aberrations and usually had opposite signs. Corneal topographic centers were displaced from aberrometer pupil centers by 0.32 ± 0.19 mm nasally and 0.02 ± 0.16 mm inferiorly; disregarding corneal decentration relative to pupil center was significant for oblique astigmatism, horizontal coma, and horizontal trefoil. An object at infinity, rather than at the image in the anterior cornea, gave incorrect aberration estimates of the posterior cornea. Corneal and lenticular aberration magnitudes are similar, and aberrations of the anterior corneal surface are approximately three times those of the posterior surface. Corneal decentration relative to pupil center has significant effects on oblique astigmatism, horizontal coma, and horizontal trefoil. When estimating component aberrations, it is important to use correct object/image conjugates and heights at surfaces.

Correlations between corneal and total wavefront aberrations

NASA Astrophysics Data System (ADS)

Mrochen, Michael; Jankov, Mirko; Bueeler, Michael; Seiler, Theo

2002-06-01

Purpose: Corneal topography data expressed as corneal aberrations are frequently used to report corneal laser surgery results. However, the optical image quality at the retina depends on all optical elements of the eye such as the human lens. Thus, the aim of this study was to investigate the correlations between the corneal and total wavefront aberrations and to discuss the importance of corneal aberrations for representing corneal laser surgery results. Methods: Thirty three eyes of 22 myopic subjects were measured with a corneal topography system and a Tschernig-type wavefront analyzer after the pupils were dilated to at least 6 mm in diameter. All measurements were centered with respect to the line of sight. Corneal and total wavefront aberrations were calculated up to the 6th Zernike order in the same reference plane. Results: Statistically significant correlations (p < 0.05) between the corneal and total wavefront aberrations were found for the astigmatism (C3,C5) and all 3rd Zernike order coefficients such as coma (C7,C8). No statistically significant correlations were found for all 4th to 6th order Zernike coefficients except for the 5th order horizontal coma C18 (p equals 0.003). On average, all Zernike coefficients for the corneal aberrations were found to be larger compared to Zernike coefficients for the total wavefront aberrations. Conclusions: Corneal aberrations are only of limited use for representing the optical quality of the human eye after corneal laser surgery. This is due to the lack of correlation between corneal and total wavefront aberrations in most of the higher order aberrations. Besides this, the data present in this study yield towards an aberration balancing between corneal aberrations and the optical elements within the eye that reduces the aberration from the cornea by a certain degree. Consequently, ideal customized ablations have to take both, corneal and total wavefront aberrations, into consideration.

Therapeutic efficacy of fibroblast growth factor 10 in a rabbit model of dry eye.

PubMed

Zheng, Wenjing; Ma, Mingming; Du, Ergang; Zhang, Zhengwei; Jiang, Kelimu; Gu, Qing; Ke, Bilian

2015-11-01

The aim of the present study was to investigate the therapeutic efficacy of fibroblast growth factor 10 (FGF10) in the promotion of healing, survival and expression of mucin in corneal epithelial cells in a rabbit dry eye model. A total of 12 healthy female New Zealand white rabbits were divided randomly into three groups. The lacrimal glands were injected with saline either alone (normal control group) or with concanavalin A (Con A), with either topical phosphate‑buffered saline (PBS; PBS control group) or 25 µg/ml FGF10 (FGF10 treatment group). Lacrimal gland inflammation, tear function, corneal epithelial cell integrity, cell apoptosis and mucin expression were subsequently assessed. Lacrimal gland tissue biopsies were performed in conjunction with histology and electron microscopy observations. Tear meniscus height (TMH) and tear meniscus area (TMA) were measured using Fourier domain‑optical coherence tomography. Tear membrane break‑up time (TBUT) was also assessed and corneal fluorescein staining was performed. The percentages of apoptotic corneal and conjunctival (Cj) epithelial cells (ECs) were counted using a terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling method. The mRNA expression levels of Muc1 were determined using reverse transcription‑quantitative polymerase chain reaction analyses. The TMH and TMA values of the PBS and treatment groups were found to be significantly reduced, compared with those of the normal control group 3 days after Con A injection. However, the TMH and TMA of the FGF10 treatment group were higher, compared with those of the PBS group 3 and 7 days after treatment, respectively. Furthermore, the FGF10 treatment group exhibited prolonged TBUT, reduced corneal fluorescein staining and repaired epithelial cell ultrastructure7 days after treatment. The percentages of apoptotic corneal‑ and Cj‑ECs in the FGF10 treatment group were significantly reduced, compared with those in the PBS group. FGF10 significantly induced the mRNA expression of Muc1 in the corneal epithelial cells, compared with the normal control group, and induced higher mRNA expression levels of Muc1 in the Cj‑ECs, compared with the PBS control group. In the present study, the rabbit dry eye model was successfully established 3 days after lacrimal gland Con A injection. FGF10 eye drops increased TMH and TMA, promoted corneal epithelial healing, reduced apoptosis of the corneal- and Cj-ECs and led to increased expression of Muc1.

[Distribution of corneal densitometry and its correlation with ocular stray light in healthy eyes].

PubMed

Wu, Zhiqing; Wang, Yan; Zhang, Lin; Wu, Di; Wei, Shengsheng; Su, Xiaolian

2014-01-01

To evaluate and investigate the distribution of corneal density and its Correlation with stray-light value in adult and healthy eyes. A prospective study. Human corneal specimens ranging in age between 20 and 49 years, 116 patients (232 eyes) in total, divided into three groups: 20-29, 30-39, 40-49. Pentacam was used to evaluate total corneal average density and corneal thickness at different diameter around the corneal apex, for corneal density were ≤ 2 mm, >2 mm and ≤ 6 mm, >6 mm and ≤ 10 mm, for corneal thickness were 2 mm, 6 mm and 10 mm, C-quant was used for the stray-light value. Software SPSS 17.0 was used for statistical analysis. Independent samples t testing method was applied to compare the corneal densitometry in different gender and between left eyes and right ones, One-way ANOVA was applied to analyze the differences of corneal density in different age groups and diameters. Pearson correlation analysis was applied to assess the correlation in corneal densitometry values of different diameters, between corneal density of different diameters and age, corneal density of different diameters and corneal thickness of different diameters, corneal density of different diameters and stray-light values. Corneal density for ≤ 2 mm, >2 mm and ≤ 6 mm, >6 mm and ≤ 10 mm diameter are 10.1 ± 1.5(8.2-16.7), 9.3 ± 1.3(7.9-14.2), 9.6 ± 1.7(7.3-16.2). Corneal density of >6 mm and ≤ 10 mm diameter in different age groups were 8.9 ± 1.1, 9.3 ± 1.2, 10.7 ± 2.1, there was a statistical difference in these values (F = 28.939, P = 0.000), and there was a positive correlation between corneal density of >6 mm and ≤ 10 mm diameter and age (r = 0.417, P = 0.000), There were no statistical differences in corneal density values of ≤ 2 mm and >2 mm and ≤ 6 mm in different age groups (F = 1.575, 1.436; P > 0.05), and they had no correlation with age (r = 0.002, 0.048; P > 0.05). There was no statistical difference in corneal density in different gender (t = 1.744, 1.647, -1.181; P > 0.05). Corneal density values of left eyes and right ones had positive relationships at the same diameter (r = 0.977, P = 0.000; r = 0.992, P = 0.000; r = 0.933, P = 0.000), and there were no statistical differences (t = 0.124, 0.199, -0.020;P > 0.05). Between corneal density values of different diameter, there are also some positive relationships, >6 mm and ≤ 10 mm and ≤ 2 mm (r = 0.710, P = 0.000), >6 mm and ≤ 10 mm and >2 mm and ≤ 6 mm (r = 0.748, P = 0.000), ≤ 2 mm and >2 mm and ≤ 6 mm (r = 0.973, P = 0.000), relationship between ≤ 2 mm and >2 mm and ≤ 6 mm, >2 mm and ≤ 6 mm and >6 mm and ≤ 10 mm was obvious, and there was statistical difference in them (F = 17.057, P = 0.000) . The ocular stray light value was 0.95 ± 0.19(0.48-1.38), Corneal density values of ≤ 2 mm, >2 mm and ≤ 6 mm and >6 mm and ≤ 10 mm diameter had positive relationships with the stray light value (r = 0.134,0.146,0.159, P = 0.042,0.026,0.016). Corneal density can be influenced by age, the influence from age infected the corneal density of peripheral more. There was no correlation between corneal density and corneal thickness. There were some influences of corneal density of healthy eyes to the ocular stray light.

Effects of artificial tear treatment on corneal epithelial thickness and corneal topography findings in dry eye patients.

PubMed

Çakır, B; Doğan, E; Çelik, E; Babashli, T; Uçak, T; Alagöz, G

2018-05-01

To investigate the effects of artificial tear treatment on central corneal epithelial thickness, and central, mid-peripheral and peripheral corneal thicknesses in patients with dry eye disease (DED). Patients with DED underwent ocular examinations, including Schirmer-2 test, slit lamp examination for tear break-up time (BUT), corneal topography (CT) for measuring mean central, mid-peripheral and peripheral corneal thickness values and anterior segment optic coherence tomography (AS-OCT) for obtaining central corneal epithelial thickness. After artificial tear treatment (carboxymethylcellulose and sodium hyaluronate formulations) for one month, patients were examined again at a second visit and the results were compared. Sixty-one eyes of 33 female dry eye patients (mean age: 38.3±5.7 years) were enrolled. The mean follow-up time was 36.4±3.3 days. The mean tear BUT and Schirmer-1 tests revealed significant improvement after treatment (P=0.000, P=0.000, respectively). Central corneal epithelium and mean mid-peripheral corneal thicknesses measured significantly higher after treatment (P=0.001, P=0.02). Changes in central and peripheral corneal thicknesses were not statistically significant. Artificial tear treatment in dry eye patients seems to increase central corneal epithelial and mid-peripheral corneal thicknesses. Measurement of corneal epithelial thickness can be a useful tool for evaluation of treatment response in dry eye patients. Further long-term prospective studies are needed to investigate this item. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Subconjunctival Bevacizumab Injection Impairs Corneal Innervations and Epithelial Wound Healing in Mice.

PubMed

Dong, Muchen; Di, Guohu; Zhang, Xiaoping; Zhou, Qingjun; Shi, Weiyun

2017-03-01

To investigate the effects of subconjunctival bevacizumab injection on the corneal nerve, sensitivity, and epithelial wound healing in mice. Adult C57BL/6 mice were treated with subconjunctival injection of 1, 2, 5, or 25 mg/mL bevacizumab. The corneal nerve was observed with whole-mount anti-β3-tubulin fluorescence staining. Corneal sensitivity was measured with a Cochet-Bonnet esthesiometer. The protein levels of pigment epithelium-derived factor (PEDF), nerve growth factor (NGF), glial-derived neurotrophic factor (GDNF), and ciliary neurotrophic factor (CNTF) were measured by ELISA. The corneal epithelial wound-healing rate was evaluated by fluorescein staining. The recovery of impaired mouse corneal innervations and epithelial wound-healing rate following bevacizumab injection was evaluated with the co-injection of PEDF, NGF, or CNTF. Subconjunctival bevacizumab injection caused apparent corneal nerve degeneration, attenuated corneal sensitivity, and delayed corneal epithelial wound healing and nerve regeneration in normal mice, which was more significant with increased concentration and times of the bevacizumab injection. However, the corneal nerve and sensitivity gradually improved and recovered in mice with a single injection of 1 to 5 mg/mL bevacizumab. Moreover, the bevacizumab injection significantly decreased the corneal PEDF, NGF, and CNTF content, whereas exogenous PEDF, NGF, or CNTF supplement attenuated impairment of the corneal nerve, sensitivity, and epithelial wound healing after subconjunctival bevacizumab injection. Subconjunctival bevacizumab injection impairs corneal innervations, epithelial wound healing, and nerve regeneration in normal mice, which may be caused by the reduction of neurotrophic factor content in the cornea.

UBIAD1 Mutation Alters a Mitochondrial Prenyltransferase to Cause Schnyder Corneal Dystrophy

PubMed Central

Nickerson, Michael L.; Kostiha, Brittany N.; Brandt, Wolfgang; Fredericks, William; Xu, Ke-Ping; Yu, Fu-Shin; Gold, Bert; Chodosh, James; Goldberg, Marc; Lu, Da Wen; Yamada, Masakazu; Tervo, Timo M.; Grutzmacher, Richard; Croasdale, Chris; Hoeltzenbein, Maria; Sutphin, John; Malkowicz, S. Bruce; Wessjohann, Ludger; Kruth, Howard S.; Dean, Michael; Weiss, Jayne S.

2010-01-01

Background Mutations in a novel gene, UBIAD1, were recently found to cause the autosomal dominant eye disease Schnyder corneal dystrophy (SCD). SCD is characterized by an abnormal deposition of cholesterol and phospholipids in the cornea resulting in progressive corneal opacification and visual loss. We characterized lesions in the UBIAD1 gene in new SCD families and examined protein homology, localization, and structure. Methodology/Principal Findings We characterized five novel mutations in the UBIAD1 gene in ten SCD families, including a first SCD family of Native American ethnicity. Examination of protein homology revealed that SCD altered amino acids which were highly conserved across species. Cell lines were established from patients including keratocytes obtained after corneal transplant surgery and lymphoblastoid cell lines from Epstein-Barr virus immortalized peripheral blood mononuclear cells. These were used to determine the subcellular localization of mutant and wild type protein, and to examine cholesterol metabolite ratios. Immunohistochemistry using antibodies specific for UBIAD1 protein in keratocytes revealed that both wild type and N102S protein were localized sub-cellularly to mitochondria. Analysis of cholesterol metabolites in patient cell line extracts showed no significant alteration in the presence of mutant protein indicating a potentially novel function of the UBIAD1 protein in cholesterol biochemistry. Molecular modeling was used to develop a model of human UBIAD1 protein in a membrane and revealed potentially critical roles for amino acids mutated in SCD. Potential primary and secondary substrate binding sites were identified and docking simulations indicated likely substrates including prenyl and phenolic molecules. Conclusions/Significance Accumulating evidence from the SCD familial mutation spectrum, protein homology across species, and molecular modeling suggest that protein function is likely down-regulated by SCD mutations. Mitochondrial UBIAD1 protein appears to have a highly conserved function that, at least in humans, is involved in cholesterol metabolism in a novel manner. PMID:20505825

Trends in the distribution of donor corneal tissue and indications for corneal transplantation: the New Zealand National Eye Bank Study 2000-2009.

PubMed

Cunningham, William J; Brookes, Nigel H; Twohill, Helen C; Moffatt, S Louise; Pendergrast, David G C; Stewart, Joanna M; McGhee, Charles N J

2012-03-01

To investigate the indications for corneal transplantation and the distribution of donor corneal tissue in New Zealand. Analysis of the prospective database of the New Zealand National Eye Bank. A total of 2205 corneal transplants were assessed. New Zealand National Eye Bank records were analysed for the decade 2000-2009. Variables analysed included donor corneal tissue distribution (including public and private sectors), indications for transplantation, donor corneal tissue recipient demographics (age and gender) and corneal transplantation type. An average of 220 corneal transplants were performed each year over the 10-year period (n=2205). The median recipient age was 45years (range 3 to 102years) and 54.0% of recipients were male. In total 71.8% of transplants were performed in the public health sector. Surgeons in the Auckland metropolitan area performed 47.2% of all corneal transplants. The most common indications for corneal transplantation were: keratoconus (41.1%), repeat transplant (17.0%), aphakic/pseudophakic bullous keratopathy (13.9%), corneal dystrophy (10.7%), keratitis (7.9%) and trauma (3.7%). Overall, penetrating keratoplasty accounted for 90.7% of all corneal transplants, however, during the latter half of the study there was a progressive shift in transplantation type, with deep anterior lamellar keratoplasty and Descemet's stripping endothelial keratoplasty combined accounting for 32.3% of all transplants in the final year of the study period. This New Zealand National Eye Bank study provides valuable data regarding the indications for corneal transplantation, transplant recipient demographics and changes in transplantation type in New Zealand over the past decade. © 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists.

Influence of posterior corneal astigmatism on postoperative refractive astigmatism in pseudophakic eyes after cataract surgery.

PubMed

Sano, Maki; Hiraoka, Takahiro; Ueno, Yuta; Itagaki, Hideo; Ogami, Tomohiro; Oshika, Tetsuro

2016-12-01

To examine the influence of posterior corneal astigmatism on postoperative refractive astigmatism in pseudophakic eyes after cataract surgery. The study enrolled 64 pseudophakic eyes of 50 patients (71.8 ± 9.9 years old, mean ± standard deviation) who had undergone phacoemulsification with non-toric IOL implantation. Refractive astigmatism was measured using an auto ref-keratometer with a 0.01- diopter (D) scale. Two types of corneal astigmatism were calculated using anterior segment optical coherence tomography; keratometric and total corneal astigmatism. Keratometric astigmatism was obtained based on anterior corneal curvature alone and total corneal astigmatism was calculated using both anterior and posterior corneal curvatures. The difference between refractive and corneal astigmatism was computed as the vector difference using 1) refractive and keratometric astigmatism and 2) refractive and total corneal astigmatism. The mean refractive, keratometric, and total corneal astigmatism was 0.92 ± 0.48 D, 0.87 ± 0.44 D, and 0.94 ± 0.46 D, respectively. The difference between refractive and keratometric astigmatism (0.70 ± 0.40 D, mean vector of 0.30 D axis 164°) was significantly larger than the difference between refractive and total corneal astigmatism (0.63 ± 0.38 D, mean vector of 0.12 D axis 137°) (P = .019). The difference between refractive and total corneal astigmatism, calculated using both anterior and posterior corneal curvatures, was significantly smaller than the difference between refractive and keratometric astigmatism using anterior corneal astigmatism alone, implying that the latter overestimates the true postoperative refractive astigmatism and can cause cylindrical inaccuracy after cataract surgery.

The relationship between corneal biomechanics and anterior segment parameters in the early stage of orthokeratology: A pilot study.

PubMed

Chen, Renai; Mao, Xinjie; Jiang, Jun; Shen, Meixiao; Lian, Yan; Zhang, Bin; Lu, Fan

2017-05-01

To investigate the relationship between corneal biomechanics and anterior segment parameters in the early stage of overnight orthokeratology.Twenty-three eyes from 23 subjects were involved in the study. Corneal biomechanics, including corneal hysteresis (CH) and corneal resistance factor (CRF), and parameters of the anterior segment, including corneal curvature, central corneal thickness (CCT), and corneal sublayers' thickness, were measured at baseline and day 1 and 7 after wearing orthokeratology lens. One-way analysis of variance with repeated measures was used to compare the longitudinal changes and partial least squares linear regression was used to explore the relationship between corneal biomechanics and anterior segment parameters.At baseline, CH and CRF were positively correlated with CCT (r = 0.244, P = .008 for CH; r = 0.249, P < .001 for CRF), central stroma thickness (CST) (r = 0.241, P = .008 for CH; r = 0.244, P = .002 for CRF) and central Bowman layer thickness (CBT) (r = 0.138, P = .039 for CH; r = 0.171, P = .006 for CRF). Both CH and CRF significantly decreased from day 1 after orthokeratology. The corneal curvature and the epithelium thickness also significantly decreased, while the stromal layer thickened significantly from day 1 after orthokeratology. There was no correlation between the changes of corneal biomechanics and anterior segment parameters at day 1 and 7 after orthokeratology.While corneal biomechanics were positively correlated with CCT, CST, and CBT, the changes of CH and CRF were not correlated with the changes of corneal curvature, CCT, and corneal sublayers' thickness in the early stage of orthokeratology in our study.

Treatment with mPEG-SPA improves the survival of corneal grafts in rats by immune camouflage.

PubMed

Wang, Shuangyong; Li, Liangliang; Liu, Ying; Li, Chaoyang; Zhang, Min; Wang, Bowen; Huang, Zheqian; Gao, Xinbo; Wang, Zhichong

2015-03-01

We investigated the immune camouflage effects of methoxy polyethylene glycol succinimidyl propionate (mPEG-SPA) on corneal antigens and explored a novel approach for reducing corneal antigenicity, thereby decreasing corneal graft rejection. Importantly, this approach did not alter normal local immunity. Corneal grafts were treated with mPEG-SPA 5KD or 20KD (3% W/V), which could shield major histocompatibility antigen class I molecules (RT1-A) of corneal grafts. Skin grafts of Wistar rats were transplanted to SD rats. Then the splenic lymphocytes were isolated from SD rats. Subsequently, the lymphocytes were co-cultured with autologous corneal grafts or untreated corneal grafts and PEGylated grafts treated with mPEG-SPA 5KD or 20KD obtained from the counterpart skin donors, which were used as autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group, respectively. Lymphocyte proliferation was lower in mPEG-SPA 5KD group and mPEG-SPA 20KD group than in the allogeneic control. SD rats with corneal neovascularisation were used as recipients for high-risk corneal transplantation and were randomly divided into four groups: autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group. The recipients received corneal grafts from Wistar rats. Corneal graft survival was prolonged and graft rejection was reduced in the mPEG-SPA 5KD group and the mPEG-SPA 20KD group compared to the allogeneic control. Thus, we think that mPEG-SPA could immunologically camouflage corneal antigens to prolong corneal grafts survival in high-risk transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Use of the Posterior/Anterior Corneal Curvature Radii Ratio to Improve the Accuracy of Intraocular Lens Power Calculation: Eom's Adjustment Method.

PubMed

Kim, Mingue; Eom, Youngsub; Lee, Hwa; Suh, Young-Woo; Song, Jong Suk; Kim, Hyo Myung

2018-02-01

To evaluate the accuracy of IOL power calculation using adjusted corneal power according to the posterior/anterior corneal curvature radii ratio. Nine hundred twenty-eight eyes from 928 reference subjects and 158 eyes from 158 cataract patients who underwent phacoemulsification surgery were enrolled. Adjusted corneal power of cataract patients was calculated using the fictitious refractive index that was obtained from the geometric mean posterior/anterior corneal curvature radii ratio of reference subjects and adjusted anterior and predicted posterior corneal curvature radii from conventional keratometry (K) using the posterior/anterior corneal curvature radii ratio. The median absolute error (MedAE) based on the adjusted corneal power was compared with that based on conventional K in the Haigis and SRK/T formulae. The geometric mean posterior/anterior corneal curvature radii ratio was 0.808, and the fictitious refractive index of the cornea for a single Scheimpflug camera was 1.3275. The mean difference between adjusted corneal power and conventional K was 0.05 diopter (D). The MedAE based on adjusted corneal power (0.31 D in the Haigis formula and 0.32 D in the SRK/T formula) was significantly smaller than that based on conventional K (0.41 D and 0.40 D, respectively; P < 0.001 and P < 0.001, respectively). The percentage of eyes with refractive prediction error within ± 0.50 D calculated using adjusted corneal power (74.7%) was significantly greater than that obtained using conventional K (62.7%) in the Haigis formula (P = 0.029). IOL power calculation using adjusted corneal power according to the posterior/anterior corneal curvature radii ratio provided more accurate refractive outcomes than calculation using conventional K.

Organ transplantation scandal influencing corneal donation rate.

PubMed

Röck, Tobias; Bramkamp, Matthias; Bartz-Schmidt, Karl Ulrich; Röck, Daniel

2017-01-01

In the majority of countries, there is a shortage of donor corneas for corneal transplantations. This study investigated the impact of organ transplantation scandals on corneal donation rate at the University Hospital Tübingen. Each deceased patient was considered as a potential corneal donor. An ophthalmic resident handled with stable methods of procedures the corneal donor procurement from 2009 to 2015. The rates of corneal donation were examined and analyzed. Among the 5712 hospital deaths, consent for corneal donation was obtained in 711 cases. The mean annual corneal donation rate was 12.4%. Since 2009, the donation rate per year could be increased with exception of 2013 and 2015. In the end of 2012 and 2014 two huge organ donation scandals were known in Germany. In the following years 2013 and 2015 corneal donation rate decreased significantly ( P =0.0181 and P =0.0006). We concluded that transplantation scandals have a significant impact on corneal donation rate. Improving professional's performance through full transparency and honesty is very important to earn trust of potential donors and their families.

Organ transplantation scandal influencing corneal donation rate

PubMed Central

Röck, Tobias; Bramkamp, Matthias; Bartz-Schmidt, Karl Ulrich; Röck, Daniel

2017-01-01

In the majority of countries, there is a shortage of donor corneas for corneal transplantations. This study investigated the impact of organ transplantation scandals on corneal donation rate at the University Hospital Tübingen. Each deceased patient was considered as a potential corneal donor. An ophthalmic resident handled with stable methods of procedures the corneal donor procurement from 2009 to 2015. The rates of corneal donation were examined and analyzed. Among the 5712 hospital deaths, consent for corneal donation was obtained in 711 cases. The mean annual corneal donation rate was 12.4%. Since 2009, the donation rate per year could be increased with exception of 2013 and 2015. In the end of 2012 and 2014 two huge organ donation scandals were known in Germany. In the following years 2013 and 2015 corneal donation rate decreased significantly (P=0.0181 and P=0.0006). We concluded that transplantation scandals have a significant impact on corneal donation rate. Improving professional's performance through full transparency and honesty is very important to earn trust of potential donors and their families. PMID:28730094

Intraoperative corneal thickness measurements during corneal collagen cross-linking with isotonic riboflavin solution without dextran in corneal ectasia.

PubMed

Cınar, Yasin; Cingü, Abdullah Kürşat; Sahin, Alparslan; Türkcü, Fatih Mehmet; Yüksel, Harun; Caca, Ihsan

2014-03-01

Abstract Objective: To monitor the changes in corneal thickness during the corneal collagen cross-linking procedure by using isotonic riboflavin solution without dextran in ectatic corneal diseases. The corneal thickness measurements were obtained before epithelial removal, after epithelial removal, following the instillation of isotonic riboflavin solution without dextran for 30 min, and after 10 min of ultraviolet A irradiation. Eleven eyes of eleven patients with progressive keratoconus (n = 10) and iatrogenic corneal ectasia (n = 1) were included in this study. The mean thinnest pachymetric measurements were 391.82 ± 30.34 µm (320-434 µm) after de-epithelialization of the cornea, 435 ± 21.17 µm (402-472 µm) following 30 min instillation of isotonic riboflavin solution without dextran and 431.73 ± 20.64 µm (387-461 µm) following 10 min of ultraviolet A irradiation to the cornea. Performing corneal cross-linking procedure with isotonic riboflavin solution without dextran might not induce corneal thinning but a little swelling throughout the procedure.

Topical administration of orbital fat-derived stem cells promotes corneal tissue regeneration.

PubMed

Lin, Ko-Jo; Loi, Mei-Xue; Lien, Gi-Shih; Cheng, Chieh-Feng; Pao, Hsiang-Yin; Chang, Yun-Chuang; Ji, Andrea Tung-Qian; Ho, Jennifer Hui-Chun

2013-06-14

Topical administration of eye drops is the major route for drug delivery to the cornea. Orbital fat-derived stem cells (OFSCs) possess an in vitro corneal epithelial differentiation capacity. Both the safety and immunomodulatory ability of systemic OFSC transplantation were demonstrated in our previous work. In this study, we investigated the safety, therapeutic effect, and mechanism(s) of topical OFSC administration in an extensive alkali-induced corneal wound. Corneal injury was created by contact of a piece of 0.5 N NaOH-containing filter paper on the corneal surface of a male Balb/c mouse for 30 s. The area of the filter paper covered the central 70% or 100% of the corneal surface. OFSCs (2 × 10(5)) in 5 μl phosphate-buffered saline (PBS) were given by topical administration (T) twice a day or by two intralimbal (IL) injections in the right cornea, while 5 μl of PBS in the left cornea served as the control. Topical OFSCs promoted corneal re-epithelialization of both the limbal-sparing and limbal-involved corneal wounds. In the first three days, topical OFSCs significantly reduced alkali-induced corneal edema and stromal infiltration according to a histopathological examination. Immunohistochemistry and immunofluorescence staining revealed that transplanted cells were easily detectable in the corneal epithelium, limbal epithelium and stroma, but only some of transplanted cells at the limbal epithelium had differentiated into cytokeratin 3-expressing cells. OFSCs did not alter neutrophil (Ly6G) levels in the cornea, but significantly reduced macrophage (CD68) infiltration and inducible nitrous oxide synthetase (iNOS) production during acute corneal injury as quantified by a Western blot analysis. Continuous topical administration of OFSCs for seven days improved corneal transparency, and this was accompanied by diffuse stromal engraftment of transplanted cells and differentiation into p63-expressing cells at the limbal area. The therapeutic effect of the topical administration of OFSCs was superior to that of the IL injection. OFSCs from the IL injection clustered in the limbal area and central corneal epithelium, which was associated with a persistent corneal haze. Topical OFSC administration is a simple, non-surgical route for stem cell delivery to promote corneal tissue regeneration through ameliorating acute inflammation and corneal epithelial differentiation. The limbal area serves as a niche for OFSCs differentiating into corneal epithelial cells in the first week, while the stroma is a potential site for anti-inflammation of OFSCs. Inhibition of corneal inflammation is related to corneal transparency.

Topical administration of orbital fat-derived stem cells promotes corneal tissue regeneration

PubMed Central

2013-01-01

Introduction Topical administration of eye drops is the major route for drug delivery to the cornea. Orbital fat-derived stem cells (OFSCs) possess an in vitro corneal epithelial differentiation capacity. Both the safety and immunomodulatory ability of systemic OFSC transplantation were demonstrated in our previous work. In this study, we investigated the safety, therapeutic effect, and mechanism(s) of topical OFSC administration in an extensive alkali-induced corneal wound. Methods Corneal injury was created by contact of a piece of 0.5 N NaOH-containing filter paper on the corneal surface of a male Balb/c mouse for 30 s. The area of the filter paper covered the central 70% or 100% of the corneal surface. OFSCs (2 × 105) in 5 μl phosphate-buffered saline (PBS) were given by topical administration (T) twice a day or by two intralimbal (IL) injections in the right cornea, while 5 μl of PBS in the left cornea served as the control. Results Topical OFSCs promoted corneal re-epithelialization of both the limbal-sparing and limbal-involved corneal wounds. In the first three days, topical OFSCs significantly reduced alkali-induced corneal edema and stromal infiltration according to a histopathological examination. Immunohistochemistry and immunofluorescence staining revealed that transplanted cells were easily detectable in the corneal epithelium, limbal epithelium and stroma, but only some of transplanted cells at the limbal epithelium had differentiated into cytokeratin 3-expressing cells. OFSCs did not alter neutrophil (Ly6G) levels in the cornea, but significantly reduced macrophage (CD68) infiltration and inducible nitrous oxide synthetase (iNOS) production during acute corneal injury as quantified by a Western blot analysis. Continuous topical administration of OFSCs for seven days improved corneal transparency, and this was accompanied by diffuse stromal engraftment of transplanted cells and differentiation into p63-expressing cells at the limbal area. The therapeutic effect of the topical administration of OFSCs was superior to that of the IL injection. OFSCs from the IL injection clustered in the limbal area and central corneal epithelium, which was associated with a persistent corneal haze. Conclusions Topical OFSC administration is a simple, non-surgical route for stem cell delivery to promote corneal tissue regeneration through ameliorating acute inflammation and corneal epithelial differentiation. The limbal area serves as a niche for OFSCs differentiating into corneal epithelial cells in the first week, while the stroma is a potential site for anti-inflammation of OFSCs. Inhibition of corneal inflammation is related to corneal transparency. PMID:23769140

Corneal collagen crosslinking and pigment dispersion syndrome.

PubMed

LaHood, Benjamin R; Moore, Sacha

2017-03-01

We describe the case of a keratoconus patient with pigment dispersion syndrome (PDS) who was treated for progressive corneal ectasia with corneal collagen crosslinking (CXL). Pigment dispersion syndrome has been shown to have associated morphologic changes of the corneal endothelium. Corneal CXL has the potential to cause toxicity to the corneal endothelium, and adjacent pigment might increase the likelihood of damage. In this case, the presence of PDS had no detrimental effect on the outcome of treatment, and no complications were observed at 12 months follow-up, indicating that it may be safe to perform corneal CXL in the setting of PDS. This is an important observation as the number of indications for corneal CXL grows. Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Consideration of growth (age)-related effects on globe size and corneal thickness in ovine eyes for use in laboratory studies.

PubMed

Doughty, Michael J

2017-07-01

The aim was to assess differences in eyeball mass, corneal diameter and central corneal thickness in slaughterhouse-procured ovine eyes. Over a 12-year period, measurements of eye globe mass, horizontal corneal diameter and central corneal thickness were routinely undertaken within two hours post-mortem. Only eyes free of obvious mechanical damage or disease were used. From measurements on 736 quality-selected and trimmed eyes, globe wet mass ranged from 10.4 to 25.2 g, horizontal corneal diameter from 19.0 to 26.5 mm and central corneal thickness measured by ultrasonic pachymetry from 0.543 to 0.836 mm (with an overall average of 690 ± 0.056 mm). The ocular globe mass was strongly correlated to horizontal corneal diameter (r 2  = 0.829). Central corneal thickness correlated with globe mass (r = 0.543) and to horizontal corneal diameter (r = 0.402). Based on the different anatomical measurements, a lamb's eye would be expected to have a thinner cornea (average 0.640 mm) than that of an adult outbred ewe (average 0.730 mm). In freshly procured eyes showing signs of slight corneal oedema, central corneal thickness was greater (average 0.856 ± 0.052 mm) and up to 24 hours of cold storage resulted in predictable increases in central corneal thickness of six to 24 per cent, especially in eyes showing signs of corneal oedema before storage. Based on the correlations obtained, differences in ovine eyes can be attributed to growth-related differences in the animals and thus, indirectly to their expected ages. A simple measure of the horizontal corneal diameter in ovine eyes used for laboratory studies would be a useful indicator in reporting these studies. © 2016 Optometry Australia.

Corneal collagen cross-linking and liposomal amphotericin B combination therapy for fungal keratitis in rabbits

PubMed Central

Hao, Zhao-Qin; Song, Jin-Xin; Pan, Shi-Yin; Zhang, Lin; Cheng, Yan; Liu, Xian-Ning; Wu, Jie; Xiao, Xiang-Hua; Gao, Wei; Zhu, Hai-Feng

2016-01-01

AIM To observe the therapeutic effect of corneal collagen cross-linking (CXL) in combination with liposomal amphotericin B in fungal corneal ulcers. METHODS New Zealand rabbits were induced fungal corneal ulcers by scratching and randomly divided into 3 groups, i.e. control, treated with CXL, and combined therapy of CXL with 0.25% liposomal amphotericin B (n=5 each). The corneal lesions were documented with slit-lamp and confocal microscopy on 3, 7, 14, 21 and 28d after treatment. The corneas were examined with transmission electron microscopy (TEM) at 4wk. RESULTS A rabbit corneal ulcer model of Fusarium was successfully established. The corneal epithelium defect areas in the two treatment groups were smaller than that in the control group on 3, 7, 14 and 21d (P<0.05). The corneal epithelium defect areas of the combined group was smaller than that of the CXL group (P<0.05) on 7 and 14d, but there were no statistical differences on 3, 21 and 28d. The corneal epithelium defects of the two treatment groups have been healed by day 21. The corneal epithelium defects of the control group were healed on 28d. The diameters of the corneal collagen fiber bundles (42.960±7.383 nm in the CXL group and 37.040±4.160 nm in the combined group) were thicker than that of the control group (24.900±1.868 nm), but there was no difference between the two treatment groups. Some corneal collagen fiber bundles were distorted and with irregular arrangement, a large number of fibroblasts could be seen among them but no inflammatory cells in both treatment groups. CONCLUSION CXL combined with liposomal amphotericin B have beneficial effects on fungal corneal ulcers. The combined therapy could alleviate corneal inflammattions, accelerate corneal repair, and shorten the course of disease. PMID:27990355

[To Protect Corneal Transparency against Diseases].

PubMed

Usui, Tomohiko

2016-03-01

To protect corneal transparency, we tried to develop a new therapeutic strategy for corneal neovascularization, corneal scar, and TGFBI-related corneal dystrophy using nucleic acid drug. 1. The expression of angiopietin-like protein 2 (Angptl2) markedly increased in the neovascularized corneas compared to the normal cornea, and Angtpl2 was(a potent inducer of inflammatory corneal neovascularization. We have produced a single-stranded proline-modified short hairpin anti-Angptl2 ribonucleric acid interference (RNAi) molecule that is carried in a lipid nanoparticle for topical application. We have found this agent can penetrate all layers of the cornea. Angptl2 mRNA expression and corneal neovascularization were inhibited in a mouse alkari injury model by topical application of this agent. Thus, this modified RNAi agent is a new topical formulation for use against corneal neovascularization and scar. 2. Human umbilical vein endothelial cells (HUVECs) were cultured with human corneal keratocytes under serum-free conditions. We performed microarray gene-expression analysis in the coculture system and selected angiopoietin-like protein 7 (Angptl7). In vivo, intrastromal injections of an anti-Angptl7 RNAi agent into the avascular corneal stroma of mice resulted in the growth of blood vessels. Further, we examined the effects of Angptl7 on corneal nerves using culture rat trigeminal cells and this molecule had neurotrophic property on the cornea. Thus, Angpt17 is a unique molecule, which contain its bilateral character (anti-angiogenic and neurotrophic) in the cornea; an agonistic nucleic acid drug for Angptl7 may be a new therapeutic tool for protecting corneal transparency. 3. We examined local gene editing for TGFBI-related corneal dystrophy using CRISPR-Cas9 mediated homology directed repair (HDR). Cultured corneal keratocytes were obtained from a patient of R124H granular dystrophy. The R124H gene arrangement was corrected by a tranfection of guide RNA and HDR repair template single strand DNA in vitro. Thus, CRISPR-Cas9 medi-ated HDR could be a future radical treatment for TGFBI-related corneal dystrophy.

[The relationship between corneal lymphangiogenesis and inflammation index after corneal alkali injury].

PubMed

Ling, Shi-qi; Li, Wei-hua; Xu, Jian-gang; Kuang, Wen-hui; Li, Chao-yang

2010-11-01

To discuss the relationship between corneal lymphangiogenesis and inflammation index (IF) in alkali burned corneas. Experimental research. Rat corneal hemangiogenesis and lymphangiogenesis were examined by 5'-nase-alkaline phosphatase (5'-NA-ALP) double enzyme-histochemistry and whole mount immunofluorescence at 1 day, 3 days, and 1, 2, 3, 4, 5, 6, 7, 8 weeks after alkaline burns, and the blood vessel counting (BVC) and the lymphatic vessel counting (LVC) were recorded. The state of corneal inflammation was observed under the slit lamp and evaluated by inflammation index (IF) grading at the same time. Then, the association of LVC with IF was examined. In addition, eleven human alkali burned corneas were obtained from 11 patients undergoing corneal transplantation in Zhongshan Ophthalmic Center from January 2005 to June 2008. Corneal lymphangiogenesis was examined by lymphatic vessel endothelial receptor (LYVE-1) immunohistochemistry. The significance of the differences in IF, inflammatory cells counting, burn history, and age between two groups was analyzed by using paired student's t-test. New lymphatic vessels were present in rat alkali burned corneas. Corneal lymphangiogenesis developed 3 days after alkaline burns, reached the top 2 weeks after the injury, then decreased gradually, and disappeared at the end of the 5th week. Corneal lymphatics occurred behind corneal inflammation, but disappeared before corneal inflammation and hemangiogenesis. LVC was strongly and positively correlated with IF (r = 0.572, P < 0.01) after corneal alkaline burns. Among eleven human alkali burned corneas, corneal lymphatic vessels were present in 3 corneas. Compared with the other 8 cases without corneal lymphangiogenesis, the scores of IF was significantly higher (t = 3.28, P < 0.05), the inflammatory cells counting dramatically increased (t = 2.42, P < 0.05), but the age decreased significantly (t = 2.62, P < 0.05). However, the difference in burn history between two groups was not significant (t = 1.28, P > 0.05). Corneal lymphangiogenesis develops after alkaline-burns and correlates closely with inflammation index.

Potential for Hospital Based Corneal Retreival in Hassan District Hospital

PubMed Central

Melsakkare, Suresh Ramappa; Manipur, Sahana R.; Acharya, Pavana; Ramamurthy, Lakshmi Bomalapura

2015-01-01

Context In developing countries, corneal diseases are the second leading cause of blindness. This corneal blindness can be treated through corneal transplantation. Though the present infrastructure is strong enough to increase keratoplasty numbers at a required rate, India has largest corneal blind population in the world. So a constant supply of high quality donor corneal tissue is the key factor for reduction of prevalence of corneal blindness. Considering the magnitude of corneal blindness and shortage of donor cornea, there is a huge gap in the demand and supply. Aim To study the potential for hospital based retrieval of donor corneal tissue in Hassan district hospital after analysing the indicated and contraindicated causes of deaths, so that hospital corneal retrieval program in Hassan district hospital can be planned. Materials and Methods The cross-sectional, retrospective and record-based study included all hospital deaths with age group more than two years occurred during one year period (January 2014 to December 2014). Data regarding demographic profile, cause of death, treatment given and presence of any systemic diseases were collected. The causes of deaths which are contraindicated for the retrieval of corneas were analysed and noted. The contraindications were based on the NPCB guidelines for standard of eye banking in India 2009. Results Out of 855 deaths, number of deaths in males (565) was greater than females (290). Numbers of deaths were highest between 41-60 years age group (343). Deaths due to HIV, septicaemia, meningitis, encephalitis, disseminated malignancies were contraindicated for corneal retrieval. Corneas could be retrieved from 736 deaths out of 855. Potential for corneal retrieval in a period of one year in Hassan District hospital was 86%. Conclusion Hospital corneal retrieval program has got a great potential to bridge the gap between the need for the cornea and actually collected corneas which will contribute enormously in eliminating corneal blindness. In present study there was 86% potential for corneal retrieval among the hospital deaths. PMID:26435976

Putting on the brakes: Bacterial impediment of wound healing

PubMed Central

Brothers, Kimberly M.; Stella, Nicholas A.; Hunt, Kristin M.; Romanowski, Eric G.; Liu, Xinyu; Klarlund, Jes K.; Shanks, Robert M. Q.

2015-01-01

The epithelium provides a crucial barrier to infection, and its integrity requires efficient wound healing. Bacterial cells and secretomes from a subset of tested species of bacteria inhibited human and porcine corneal epithelial cell migration in vitro and ex vivo. Secretomes from 95% of Serratia marcescens, 71% of Pseudomonas aeruginosa, 29% of Staphylococcus aureus strains, and other bacterial species inhibited epithelial cell migration. Migration of human foreskin fibroblasts was also inhibited by S. marcescens secretomes indicating that the effect is not cornea specific. Transposon mutagenesis implicated lipopolysaccharide (LPS) core biosynthetic genes as being required to inhibit corneal epithelial cell migration. LPS depletion of S. marcescens secretomes with polymyxin B agarose rendered secretomes unable to inhibit epithelial cell migration. Purified LPS from S. marcescens, but not from Escherichia coli or S. marcescens strains with mutations in the waaG and waaC genes, inhibited epithelial cell migration in vitro and wound healing ex vivo. Together these data suggest that S. marcescens LPS is sufficient for inhibition of epithelial wound healing. This study presents a novel host-pathogen interaction with implications for infections where bacteria impact wound healing and provides evidence that secreted LPS is a key factor in the inhibitory mechanism. PMID:26365869

Stem cells and corneal epithelial maintenance – insights from the mouse and other animal models

PubMed Central

Mort, Richard L.; Douvaras, Panagiotis; Morley, Steven D.; Dorà, Natalie; Hill, Robert E.; Collinson, J. Martin; West, John D.

2012-01-01

Maintenance of the corneal epithelium is essential for vision and is a dynamic process incorporating constant cell production, movement and loss. Although cell based therapies involving the transplantation of putative stem cells are well advanced for the treatment of human corneal defects, the scientific understanding of these interventions is poor. No definitive marker that discriminates stem cells that maintain the corneal epithelium from the surrounding tissue has been discovered and the identity of these elusive cells is, therefore, hotly debated. The key elements of corneal epithelial maintenance have long been recognised but it is still not known how this dynamic balance is coordinated during normal homeostasis to ensure the corneal epithelium is maintained at a uniform thickness. Most indirect experimental evidence supports the limbal epithelial stem cell (LESC) hypothesis, which proposes that the adult corneal epithelium is maintained by stem cells located in the limbus at the corneal periphery. However, this has been challenged recently by the corneal epithelial stem cell (CESC) hypothesis, which proposes that during normal homeostasis the mouse corneal epithelium is maintained by stem cells located throughout the basal corneal epithelium with LESCs only contributing during wound healing. In this chapter we review experimental studies, mostly based on animal work, that provide insights into how stem cells maintain the normal corneal epithelium and consider the merits of the alternative LESC and CESC hypotheses. Finally, we highlight some recent research on other stem cell systems and consider how this could influence future research directions for identifying the stem cells that maintain the corneal epithelium. PMID:22918816

Evaluation of ABCG2 and p63 expression in canine cornea and cultivated corneal epithelial cells.

PubMed

Morita, Maresuke; Fujita, Naoki; Takahashi, Ayaka; Nam, Eun Ryel; Yui, Sho; Chung, Cheng Shu; Kawahara, Naoya; Lin, Hsing Yi; Tsuzuki, Keiko; Nakagawa, Takayuki; Nishimura, Ryohei

2015-01-01

To examine the expressions of ABCG2 and p63 in canine corneal epithelia and to evaluate their significance in corneal regeneration. Canine corneal and limbal epithelial cells were obtained from five healthy beagle dogs. We analyzed the morphological properties of cultivated limbal and corneal epithelial cells. We compared the expressions of ABCG2 and p63 in the limbus and central cornea by immunohistochemistry and real-time quantitative PCR. We analyzed the expression of these markers in cultivated cells by immunocytochemistry and real-time quantitative PCR. The limbal epithelial cells were smaller and proliferated more rapidly than the corneal epithelial cells in primary cultures. The corneal cells failed to be subcultured, whereas the limbal cells could be subcultured with increasing cell size. ABCG2 was localized in the basal layer of the limbal epithelium, and p63 was widely detected in the entire corneal epithelia. ABCG2 expression was significantly higher, and p63 was slightly higher in the limbus compared with the central cornea. ABCG2 was detected only in limbal cells in primary culture, not in corneal cells or passaged limbal cells. p63 was detected in both limbal and corneal cells and decreased gradually in the limbal cells with the cell passages. ABCG2 was localized in canine limbal epithelial cells, and p63 was widely expressed in canine corneal epithelia. ABCG2 and p63 could prove to be useful markers in dogs for putative corneal epithelial stem cells and for corneal epithelial cell proliferation, respectively. © 2014 American College of Veterinary Ophthalmologists.

Analysis of correlation between corneal topographical data and visual performance

NASA Astrophysics Data System (ADS)

Zhou, Chuanqing; Yu, Lei; Ren, Qiushi

2007-02-01

Purpose: To study correlation among corneal asphericity, higher-order aberrations and visual performance for eyes of virgin myopia and postoperative laser in situ keratomileusis (LASIK). Methods: There were 320 candidates 590 eyes for LASIK treatment included in this study. The mean preoperative spherical equivalence was -4.35+/-1.51D (-1.25 to -9.75), with astigmatism less than 2.5 D. Corneal topography maps and contrast sensitivity were measured and analyzed for every eye before and one year after LASIK for the analysis of corneal asphericity and wavefront aberrations. Results: Preoperatively, only 4th and 6th order aberration had significant correlation with corneal asphericity and apical radius of curvature (p<0.001). Postoperatively, all 3th to 6th order aberrations had statistically significant correlation with corneal asphericity (p<0.01), but only 4th and 6th order aberration had significant correlation with apical radius of curvature (p<0.05). The asymmetrical aberration like coma had significant correlation with vertical offset of pupil center (p<0.01). Preoperatively, corneal aberrations had no significant correlation with visual acuity and area under the log contrast sensitivity (AULCSF) (P>0.05). Postoperatively, corneal aberrations still didn't have significant correlation with visual acuity (P>0.05), but had significantly negative correlation with AULCSF (P<0.01). Corneal asphericity had no significant correlation with AULCSF before and after the treatment (P>0.05). Conclusions: Corneal aberrations had different correlation with corneal profile and visual performance for eyes of virgin myopia and postoperative LASIK, which may be due to changed corneal profile and limitation of metrics of corneal aberrations.

Pirfenidone Nanoparticles Improve Corneal Wound Healing and Prevent Scarring Following Alkali Burn

PubMed Central

Chowdhury, Sushovan; Guha, Rajdeep; Trivedi, Ruchit; Kompella, Uday B.; Konar, Aditya; Hazra, Sarbani

2013-01-01

Purpose To evaluate the effects of pirfenidone nanoparticles on corneal re-epithelialization and scarring, major clinical challenges after alkali burn. Methods Effect of pirfenidone on collagen I and α-smooth muscle actin (α-SMA) synthesis by TGFβ induced primary corneal fibroblast cells was evaluated by immunoblotting and immunocytochemistry. Pirfenidone loaded poly (lactide-co-glycolide) (PLGA) nanoparticles were prepared, characterized and their cellular entry was examined in primary corneal fibroblast cells by fluorescence microscopy. Alkali burn was induced in one eye of Sprague Dawley rats followed by daily topical treatment with free pirfenidone, pirfenidone nanoparticles or vehicle. Corneal re-epithelialization was assessed daily by flourescein dye test; absence of stained area indicated complete re-epithelialization and the time for complete re-epithelialization was determined. Corneal haze was assessed daily for 7 days under slit lamp microscope and graded using a standard method. After 7 days, collagen I deposition in the superficial layer of cornea was examined by immunohistochemistry. Results Pirfenidone prevented (P<0.05) increase in TGF β induced collagen I and α-SMA synthesis by corneal fibroblasts in a dose dependent manner. Pirfenidone could be loaded successfully within PLGA nanoparticles, which entered the corneal fibroblasts within 5 minutes. Pirfenidone nanoparticles but not free pirfenidone significantly (P<0.05) reduced collagen I level, corneal haze and the time for corneal re-epithelialization following alkali burn. Conclusion Pirfenidone decreases collagen synthesis and prevents myofibroblast formation. Pirfenidone nanoparticles improve corneal wound healing and prevent fibrosis. Pirfenidone nanoparticles are of potential value in treating corneal chemical burns and other corneal fibrotic diseases. PMID:23940587

Photorefractive keratectomy in the cat eye: biological and optical outcomes.

PubMed

Nagy, Lana J; MacRae, Scott; Yoon, Geunyoung; Wyble, Matthew; Wang, Jianhua; Cox, Ian; Huxlin, Krystel R

2007-06-01

To quantify optical and biomechanical properties of the feline cornea before and after photorefractive keratectomy (PRK) and assess the relative contribution of different biological factors to refractive outcome. Department of Ophthalmology, University of Rochester, Rochester, New York, USA. Adult cats had 6.0 diopter (D) myopic or 4.0 D hyperopic PRK over 6.0 or 8.0 mm optical zones (OZ). Preoperative and postoperative wavefront aberrations were measured, as were intraocular pressure (IOP), corneal hysteresis, the corneal resistance factor, axial length, corneal thickness, and radii of curvature. Finally, postmortem immunohistochemistry for vimentin and alpha-smooth muscle actin was performed. Photorefractive keratectomy changed ocular defocus, increased higher-order aberrations, and induced myofibroblast differentiation in cats. However, the intended defocus corrections were only achieved with 8.0 mm OZs. Long-term flattening of the epithelial and stromal surfaces was noted after myopic, but not after hyperopic, PRK. The IOP was unaltered by PRK; however, corneal hysteresis and the corneal resistance factor decreased. Over the ensuing 6 months, ocular aberrations and the IOP remained stable, while central corneal thickness, corneal hysteresis, and the corneal resistance factor increased toward normal levels. Cat corneas exhibited optical, histological, and biomechanical reactions to PRK that resembled those previously described in humans, especially when the OZ size was normalized to the total corneal area. However, cats exhibited significant stromal regeneration, causing a return to preoperative corneal thickness, corneal hysteresis and the corneal resistance factor without significant regression of optical changes induced by the surgery. Thus, the principal effects of laser refractive surgery on ocular wavefront aberrations can be achieved despite clear interspecies differences in corneal biology.

[Post-lasik corneal ectasia in patients with significant differences in keratometry readings between both eyes].

PubMed

Ortega-Usobiaga, J; Llovet-Osuna, F; Djodeyre, M R; Llovet-Rausell, A; Beltran-Sanz, J; Baviera-Sabater, J

2014-03-01

A study is made on the incidence of corneal ectasia after laser in situ keratomileusis (LASIK) in patients with large differences in mean keratometry (MK) readings between both eyes (OU). Visual outcomes were also evaluated. The medical records of 164,603 patients (315,259 eyes) who underwent LASIK from January 2003 to December 2011 were reviewed in order to identify patients with a difference in MK of ≥ 1.25 D between OU. The main outcome measures were incidence of ectasia after LASIK, and visual outcome. A total of 35 eyes that met the inclusion criteria were found. Functional and visual results were those expected for myopia studies. After a minimum follow-up of 2 years, no corneal ectasia was found in 3 eyes (2 patients). The possibility of finding a patient with an asymmetry in MK and normal topography is low (0.021%), and it does not seem to be a contraindication of LASIK. Although no corneal ectasia was found in this case series, and as it is a potentially sight-threatening complication, patients with very different MK between OU should be studied carefully before undergoing LASIK. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Mini-Review: Limbal Stem Cells Deficiency in Companion Animals: Time to Give Something Back?

PubMed

Sanchez, Rick F; Daniels, Julie T

2016-04-01

Experimental animals have been used extensively in the goal of developing sight-saving therapies for humans. One example is the development of transplantation of cultured limbal epithelial stem cells (LESC) to restore vision following ocular surface injury or disease. With clinical trials of cultured LESC therapy underway in humans and a potential companion animal population suffering from similar diseases, it is perhaps time to give something back. Comparatively to humans, what is known about the healthy limbus and corneal surface physiology of companion animals is still very little. Blinding corneal diseases in animals such as symblepharon in cats with Feline Herpes Virus-1 infections require a basic understanding of the functional companion animal limbus and corneal stem cells. Our understanding of many other vision threatening conditions such as scarring of the cornea post-inflammation with lymphocytic-plasmacytic infiltrate in dogs (aka chronic superficial keratitis) or pigment proliferation with Pigmentary Keratitis of Pugs would benefit from a better understanding of the animal cornea in health and disease. This is also vital when new therapeutic approaches are considered. This review will explore the current challenges and future research directions that will be required to increase our understanding of corneal diseases in animals and consider the potential development and delivery of cultured stem cell therapy to veterinary ocular surface patients.

Relationship of Corneal Pain Sensitivity With Dry Eye Symptoms in Dry Eye With Short Tear Break-Up Time.

PubMed

Kaido, Minako; Kawashima, Motoko; Ishida, Reiko; Tsubota, Kazuo

2016-03-01

The purpose of this prospective comparative study was to investigate corneal sensitivity in subjects with unstable tear film, with and without dry eye (DE) symptoms. Forty-one eyes of 41 volunteers (mean age: 45.1 ± 9.4 years; age range, 23-57 years), with normal tear function and ocular surface except for tear stability, were studied. The eyes were divided into two groups depending on the presence or absence of DE symptoms: 21 eyes with DE symptoms (symptomatic group); and 20 eyes without DE symptoms (asymptomatic group). Three types of corneal sensitivity values were measured using a Cochet-Bonnet esthesiometer: the sensitivity for perception of touch (S-touch), the sensitivity for blinking (S-blink), and the sensitivity for pain (S-pain). Mean S-blink and S-pain were significantly higher in the symptomatic group than in the asymptomatic group (P < 0.05), whereas there was no significant difference in mean S-touch between these groups (P > 0.05). Corneal sensitivity for blinking and pain evoked by increased stimuli was higher in the symptomatic group (subjects with short break-up time DE) compared with subjects who have no DE symptoms despite decreased tear stability. The presence of both tear instability and hyperesthesia, rather than tear instability alone, may contribute to DE pathogenesis.

Efficacy of anti-inflammatory, antibiotic and pleiotropic agents in reversing nitrogen mustard-induced injury in ex vivo cultured rabbit cornea.

PubMed

Goswami, Dinesh G; Kant, Rama; Tewari-Singh, Neera; Agarwal, Rajesh

2018-09-01

Vesicating agent, Sulfur mustard (SM), causes devastating eye injury; however, there are no effective antidotes available. Using nitrogen mustard (NM), a bi-functional analog of SM, we have earlier reported that NM-induced corneal injury in ex vivo rabbit cornea organ culture model parallels corneal injury reported with SM. Using this model, we have demonstrated the therapeutic efficacy of dexamethasone (DEX), doxycycline (DOX) and silibinin (SB) in reversing NM (2h exposure)-induced corneal injuries when added immediately after washing NM. In the present study, we further examined the efficacy of similar/higher doses of these agents when added immediately, 2, or 4h after washing NM following its 2h exposure. All three treatment agents caused a reversal in established NM-induced injury biomarkers when added immediately or 2h after washing NM following its 2h exposure; however, when treatments were carried out 4h after washing NM, there was no significant effect. Together, our results further show the beneficial effect of these agents in reversing NM-induced corneal injury and indicate the time window for effective treatment. This could be useful towards future development of targeted therapeutics against vesicant-induced ocular injury. Copyright © 2017 Elsevier B.V. All rights reserved.

An ErbB2-Muc4 complex in rat ocular surface epithelia.

PubMed

Swan, Jeremy S; Arango, Maria E; Carothers Carraway, Coralie A; Carraway, Kermit L

2002-05-01

To show the presence and localization of type 1 growth factor receptors (ErbB2, ErbB3 and ErbB4) in rat corneal and conjunctival epithelia and investigate the association of ErbB2 with its intramembrane ligand Muc4. Methacarn-fixed, paraffin-embedded sections of corneas and eyelids from female adult rats were immunocytochemically stained using antibodies against the ErbB receptors and Muc4. Sequential immunoprecipitation and immunoblot analyses were performed on epithelial lysates to investigate the presence of a complex of Muc4 and ErbB2 in corneal and conjunctival epithelia. Immunocytochemical staining demonstrated the presence of ErbB2, ErbB3 and ErbB4 growth factor receptors throughout the rat corneal and conjunctival epithelia. Co-immunoprecipitation of the epithelial lysates demonstrated that Muc4 and ErbB2 are present as a complex. The three type 1 growth factor receptors (ErbB2, ErbB3 and ErbB4) are present in the rat corneal and conjunctival epithelia, and ErbB2 is at least partly associated with Muc4. This demonstration of the presence and localization of these three type 1 growth factor receptors may help in understanding how these receptors contribute to ocular epithelial behavior and functions.

Differential Effects of Hormones on Cellular Metabolism in Keratoconus In Vitro

PubMed Central

McKay, Tina B.; Hjortdal, Jesper; Sejersen, Henrik; Karamichos, Dimitrios

2017-01-01

Keratoconus (KC) is a corneal thinning disease with an onset commonly immediately post-puberty and stabilization by 40 to 50 years of age. The role of hormones in regulating corneal tissue structure in homeostatic and pathological conditions is unknown. Our group recently linked altered hormone levels to KC. Our current study sought to investigate and delineate the effects of exogenous hormones, such as androgen, luteotropin, and estrogen, on corneal stroma bioenergetics. We utilized our established 3D in vitro model to characterize the effects of DHEA, prolactin, 17β-estradiol on insulin-growth factor-1 and -2 (IGF-1, -2) signaling and metabolic function in primary corneal fibroblasts from healthy controls (HCFs) and KC patients (HKCs). Our data showed that exogenous DHEA significantly downregulated IGF-1 and its receptor in both HCFs and HKCs with HKCs showing consistently lower basal pentose phosphate flux. Prolactin caused no significant change in IGF-1 levels and an increase in IGF-2 in HKCs correlating with an increase in ATP and NADH levels. 17β-estradiol led to a significant upregulation in pentose phosphate flux and glycolytic intermediates in HCFs. Our results identified hormone-specific responses regulated in HKCs compared to HCFs revealing a novel role for hormones on bioenergetics in KC. PMID:28211546

Retinoic Acid Engineered Amniotic Membrane Used as Graft or Homogenate: Positive Effects on Corneal Alkali Burns.

PubMed

Joubert, Romain; Daniel, Estelle; Bonnin, Nicolas; Comptour, Aurélie; Gross, Christelle; Belville, Corinne; Chiambaretta, Frédéric; Blanchon, Loïc; Sapin, Vincent

2017-07-01

Alkali burns are the most common, severe chemical ocular injuries, their functional prognosis depending on corneal wound healing efficiency. The purpose of our study was to compare the benefits of amniotic membrane (AM) grafts and homogenates for wound healing in the presence or absence of previous all-trans retinoic acid (atRA) treatment. Fifty male CD1 mice with reproducible corneal chemical burn were divided into five groups, as follows: group 1 was treated with saline solution; groups 2 and 3 received untreated AM grafts or grafts treated with atRA, respectively; and groups 4 and 5 received untreated AM homogenates or homogenates treated with atRA, respectively. After 7 days of treatment, ulcer area and depth were measured, and vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) were quantified. AM induction by atRA was confirmed via quantification of retinoic acid receptor β (RARβ), a well-established retinoic acid-induced gene. Significant improvements of corneal wound healing in terms of ulcer area and depth were obtained with both strategies. No major differences were found between the efficiency of AM homogenates and grafts. This positive action was increased when AM was pretreated with atRA. Furthermore, AM induced a decrease in VEGF and MMP-9 levels during the wound healing process. The atRA treatment led to an even greater decrease in the expression of both proteins. Amnion homogenate is as effective as AM grafts in promoting corneal wound healing in a mouse model. A higher positive effect was obtained with atRA treatment.

Mitochondrial and Morphologic Alterations in Native Human Corneal Endothelial Cells Associated With Diabetes Mellitus.

PubMed

Aldrich, Benjamin T; Schlötzer-Schrehardt, Ursula; Skeie, Jessica M; Burckart, Kimberlee A; Schmidt, Gregory A; Reed, Cynthia R; Zimmerman, M Bridget; Kruse, Friedrich E; Greiner, Mark A

2017-04-01

To characterize changes in the energy-producing metabolic activity and morphologic ultrastructure of corneal endothelial cells associated with diabetes mellitus. Transplant suitable corneoscleral tissue was obtained from donors aged 50 to 75 years. We assayed 3-mm punches of endothelium-Descemet membrane for mitochondrial respiration and glycolysis activity using extracellular flux analysis of oxygen and pH, respectively. Transmission electron microscopy was used to assess qualitative and quantitative ultrastructural changes in corneal endothelial cells and associated Descemet membrane. For purposes of analysis, samples were divided into four groups based on a medical history of diabetes regardless of type: (1) nondiabetic, (2) noninsulin-dependent diabetic, (3) insulin-dependent diabetic, and (4) insulin-dependent diabetic with specified complications due to diabetes (advanced diabetic). In total, 229 corneas from 159 donors were analyzed. Insulin-dependent diabetic samples with complications due to diabetes displayed the lowest spare respiratory values compared to all other groups (P ≤ 0.002). The remaining mitochondrial respiration and glycolysis metrics did not differ significantly among groups. Compared to nondiabetic controls, the endothelium from advanced diabetic samples had alterations in mitochondrial morphology, pronounced Golgi bodies associated with abundant vesicles, accumulation of lysosomal bodies/autophagosomes, and focal production of abnormal long-spacing collagen. Extracellular flux analysis suggests that corneal endothelial cells of donors with advanced diabetes have impaired mitochondrial function. Metabolic findings are supported by observed differences in mitochondrial morphology of advanced diabetic samples but not controls. Additional studies are needed to determine the precise mechanism(s) by which mitochondria become impaired in diabetic corneal endothelial cells.

Risk factors for low vision related functioning in the Mycotic Ulcer Treatment Trial: a randomised trial comparing natamycin with voriconazole

PubMed Central

Rose-Nussbaumer, Jennifer; Prajna, N Venkatesh; Krishnan, Tiruvengada; Mascarenhas, Jeena; Rajaraman, Revathi; Srinivasan, Muthiah; Raghavan, Anita; Oldenburg, Catherine E; O’Brien, Kieran S; Ray, Kathryn J; Porco, Travis C; McLeod, Stephen D; Acharya, Nisha R; Keenan, Jeremy D; Lietman, Thomas M

2016-01-01

Background/aims The Mycotic Ulcer Treatment Trial I (MUTT I) was a double-masked, multicentre, randomised controlled trial, which found that topical natamycin is superior to voriconazole for the treatment of filamentous fungal corneal ulcers. In this study, we determine risk factors for low vision-related quality of life in patients with fungal keratitis. Methods The Indian visual function questionnaire (IND-VFQ) was administered to MUTT I study participants at 3 months. Associations between patient and ulcer characteristics and IND-VFQ subscale score were assessed using generalised estimating equations. Results 323 patients were enrolled in the trial, and 292 (90.4%) completed the IND-VFQ at 3 months. Out of a total possible score of 100, the average VFQ score for all participants was 81.3 (range 0–100, SD 23.6). After correcting for treatment arm, each logMAR line of worse baseline visual acuity in the affected eye resulted in an average 1.2 points decrease on VFQ at 3 months (95% CI −1.8 to 0.6, p<0.001). Those who required therapeutic penetrating keratoplasty had an average of 25.2 points decrease on VFQ after correcting for treatment arm (95% CI −31.8 to −18.5, p<0.001). Study participants who were unemployed had on average 28.5 points decrease on VFQ (95% CI −46.9 to −10.2, p=0.002) after correcting for treatment arm. Conclusions Monocular vision loss from corneal opacity due to fungal keratitis reduced vision-related quality of life. Given the relatively high worldwide burden of corneal opacity, improving treatment outcomes of corneal infections should be a public health priority. Trial registration number Clinicaltrials.gov Identifier: NCT00996736. PMID:26531051

Corneal and conjunctival sensory function: the impact on ocular surface sensitivity of change from low to high oxygen transmissibility contact lenses.

PubMed

Golebiowski, Blanka; Papas, Eric B; Stapleton, Fiona

2012-03-09

Deprivation of oxygen to the ocular surface during contact lens wear has been implicated in the alteration of sensory function. This study investigates whether increasing oxygen availability through discontinuation of contact lens wear or transfer into highly oxygen transmissible (high Dk/t) lenses leads to a change in corneal or conjunctival sensitivity. Twenty-seven long-term extended wearers of low Dk/t soft contact lenses ceased lens wear for 1 week and were refitted with high Dk/t silicone hydrogel lenses. A control group of 25 nonwearers matched for age and sex was also recruited. Central corneal and inferior conjunctival sensitivity were measured using an air-jet aesthesiometer. Threshold was determined using a staircase technique. Measurements were taken during low Dk/t lens wear; after 1 week of no wear; and after 1, 3, 6, and 12 months of high Dk/t lens wear. Measurements were carried out on one occasion on the nonwearers. Corneal sensitivity decreased 1 week after discontinuation of low Dk/t lenses and no further change in sensitivity occurred with high Dk/t lens wear. Conjunctival sensitivity did not change over the same time frame. Ocular surface sensitivity in long-term low Dk/t soft lens wearers was similar to that of nonwearers. Sensitivity was higher in females than males in the nonwearers, but not in the lens-wearing group. An interaction of sex on change in conjunctival threshold was found in the lens wearers. These findings indicate that factors other than oxygen availability alone determine sensitivity of the ocular surface. Silicone hydrogel contact lenses appear to have only a minor impact on ocular surface sensitivity in previous lens wearers.

Electrolysis for corneal opacities in a young patient with superficial variant of granular corneal dystrophy (Reis-Bücklers corneal dystrophy).

PubMed

Kamoi, Mizuka; Mashima, Yukihiko; Kawashima, Motoko; Tsubota, Kazuo

2005-06-01

To report the efficacy of electrolysis as a treatment of corneal opacities in a young patient with the superficial variant of granular corneal dystrophy. Interventional case report. An 11-year-old boy presented with subepithelial opacities in both eyes. His visual acuity was 0.2 in the left eye; he received corneal electrolysis under topical anesthesia. The electrolysis, which required only 5 minutes, resulted in the disappearance of the subepithelial opacities. His visual acuity improved to 0.4 on the next day and was 1.0 eight months later. The corneal curvature and thickness were not altered by the electrolysis. Corneal electrolysis proved to be an effective treatment for subepithelial opacities, and we recommend electrolysis as an effective and simple treatment for young patients with SGCD.

Automated boundary segmentation and wound analysis for longitudinal corneal OCT images

NASA Astrophysics Data System (ADS)

Wang, Fei; Shi, Fei; Zhu, Weifang; Pan, Lingjiao; Chen, Haoyu; Huang, Haifan; Zheng, Kangkeng; Chen, Xinjian

2017-03-01

Optical coherence tomography (OCT) has been widely applied in the examination and diagnosis of corneal diseases, but the information directly achieved from the OCT images by manual inspection is limited. We propose an automatic processing method to assist ophthalmologists in locating the boundaries in corneal OCT images and analyzing the recovery of corneal wounds after treatment from longitudinal OCT images. It includes the following steps: preprocessing, epithelium and endothelium boundary segmentation and correction, wound detection, corneal boundary fitting and wound analysis. The method was tested on a data set with longitudinal corneal OCT images from 20 subjects. Each subject has five images acquired after corneal operation over a period of time. The segmentation and classification accuracy of the proposed algorithm is high and can be used for analyzing wound recovery after corneal surgery.

Effect of Cycloplegia on Corneal Biometrics and Refractive State.

PubMed

Bagheri, Abbas; Feizi, Mohadeseh; Shafii, Aliakbar; Faramarzi, Amir; Tavakoli, Mehdi; Yazdani, Shahin

2018-01-01

To determine changes in refractive state and corneal parameters after cycloplegia with cyclopentolate hydrochloride 1% using a dual Scheimpflug imaging system. In this prospective cross-sectional study patients aged 10 to 40 years who were referred for optometric evaluation enrolled and underwent autorefraction and corneal imaging with the Galilei dual Scheimpflug system before and 30 minutes after twice instillation of medication. Changes in refraction and astigmatism were investigated. Corneal biometrics including anterior and posterior corneal curvatures, total corneal power and corneal pachymetry were compared before and after cycloplegia. Two hundred and twelve eyes of 106 subjects with mean age of 28 ± 5 years including 201 myopic and 11 hyperopic eyes were evaluated. Mean spherical equivalent refractive error before cycloplegia was -3.4 ± 2.6 D. A mean hyperopic shift of 0.4 ± 0.5 D occurred after cycloplegia ( P < 0.001). The astigmatism power did not significantly change ( P = 0.8), however, 26.8% of eyes with significant astigmatism experienced a change of more than 5 degrees in the axis of astigmatism. Changes in posterior corneal curvature were scant but statistically significant ( P = 0.001). Moreover, corneal thickness was slightly increased in the central and paracentral regions ( P < 0.001 and P < 0.001, respectively). Cycloplegia causes a hyperopic shift and astigmatism axis changes, along with an increase in central and paracentral corneal thickness and change in posterior corneal curvature. The effects of cycloplegia on refraction and corneal biometrics should be considered before cataract and refractive surgeries.

Topical treatment of corneal alkali burns with Gly-thymosin β4 solutions and in situ hydrogels via inhibiting corneal neovascularization and improving corneal epidermal recovery in experimental rabbits.

PubMed

Zhang, Weili; Nie, Liya; Du, Lina; Chen, Wenyang; Wu, Zhihong; Jin, Yiguang

2017-12-01

Corneal alkali burns are a severe disease and commonly encountered in the emergent clinic. A rapid medical treatment for the burn is very important. Gly-thymosin β 4 (Gly-Tβ 4 ) is a biomimic derivative of natural thymosin β 4 . The aim of this study is to evaluate the corneal recovery effects of Gly-Tβ 4 topical therapy on alkali burns in rabbit corneas. Rabbit alkali burns were induced with NaOH-contained filter paper. Phosphate-buffered solutions at pH 7.0, Gly-Tβ 4 solutions, blank in situ hydrogels, and Gly-Tβ 4 in situ hydrogels were dropped on the burned corneas. The treatments were continued for 14 days. Conjunctiva hyperemia, corneal edema, intraeye extravasation, hemorrhaging, corneal neovascularization (CNV), and corneal opacity were observed. Corneal immunohistochemistry and histopathology were performed. Gly-Tβ 4 solutions led to a lower corneal burn index than the other regimens. Hydrogels may stimulate the burned corneas due to the direct contact of them, and prevent the rapid release of Gly-Tβ 4 . Gly-Tβ 4 significantly inhibited CNV according to the images of the corneas, CNV areas, and CD31 expression. Furthermore, Gly-Tβ 4 improved corneal epidermal recovery according to the histopathological result. Gly-Tβ 4 solutions are a promising formulation for topical treatment of corneal alkali burns. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

New therapeutic modality for corneal endothelial disease using Rho-associated kinase inhibitor eye drops.

PubMed

Koizumi, Noriko; Okumura, Naoki; Ueno, Morio; Kinoshita, Shigeru

2014-11-01

Corneal endothelial dysfunction accompanied by visual disturbance is a primary indication for corneal endothelial transplantation. However, despite the value and potential of endothelial graft surgery, a strictly pharmacological approach for treating corneal endothelial dysfunction remains an attractive proposition. Previously, we reported that the selective Rho-associated kinase (ROCK) inhibitor Y-27632 promotes cell adhesion and proliferation, and inhibits the apoptosis of primate corneal endothelial cells in culture. These findings have led us to develop a novel medical treatment for the early phase of corneal endothelial disease using ROCK inhibitor eye drops. In rabbit and monkey models of partial endothelial dysfunction, we showed that corneal endothelial wound healing was accelerated via the topical application of ROCK inhibitor to the ocular surface, resulting in the regeneration of a corneal endothelial monolayer with a high endothelial cell density. Based on these animal studies, we are now attempting to advance the clinical application of ROCK inhibitor eye drops for patients with corneal endothelial dysfunction. A pilot clinical study was performed at the Kyoto Prefectural University of Medicine, and the effects of Y-27632 eye drops after transcorneal freezing were evaluated in 8 patients with corneal endothelial dysfunction. We observed a positive effect of ROCK inhibitor eye drops in treating patients with central edema caused by Fuchs corneal endothelial dystrophy. We believe that our new findings will contribute to the establishment of a new approach for the treatment of corneal endothelial dysfunction.

Mucin deficiency causes functional and structural changes of the ocular surface.

PubMed

Floyd, Anne M; Zhou, Xu; Evans, Christopher; Rompala, Olivia J; Zhu, Lingxiang; Wang, Mingwu; Chen, Yin

2012-01-01

MUC5AC is the most abundant gel-forming mucin in the ocular system. However, the specific function is unknown. In the present study, a Muc5ac knockout (KO) mouse model was subject to various physiological measurements as compared to its wide-type (WT) control. Interestingly, when KO mice were compared to WT mice, the mean tear break up time (TBUT) values were significantly lower and corneal fluorescein staining scores were significantly higher. But the tear volume was not changed. Despite the lack of Muc5ac expression in the conjunctiva of KO mice, Muc5b expression was significantly increased in these mice. Corneal opacification, varying in location and severity, was found in a few KO mice but not in WT mice. The present results suggest a significant difference in the quality, but not the quantity, of tear fluid in the KO mice compared to WT mice. Dry eye disease is multifactorial and therefore further evaluation of the varying components of the tear film, lacrimal unit and corneal structure of these KO mice may help elucidate the role of mucins in dry eye disease. Because Muc5ac knockout mice have clinical features of dry eye, this mouse model will be extremely useful for further studies regarding the pathophysiology of the ocular surface in dry eye in humans.

Wavelength dependence of ocular damage thresholds in the near-ir to far-ir transition region: proposed revisions to MPES.

PubMed

Zuclich, Joseph A; Lund, David J; Stuck, Bruce E

2007-01-01

This report summarizes the results of a series of infrared (IR) laser-induced ocular damage studies conducted over the past decade. The studies examined retinal, lens, and corneal effects of laser exposures in the near-IR to far-IR transition region (wavelengths from 1.3-1.4 mum with exposure durations ranging from Q-switched to continuous wave). The corneal and retinal damage thresholds are tabulated for all pulsewidth regimes, and the wavelength dependence of the IR thresholds is discussed and contrasted to laser safety standard maximum permissible exposure limits. The analysis suggests that the current maximum permissible exposure limits could be beneficially revised to (1) relax the IR limits over wavelength ranges where unusually high safety margins may unintentionally hinder applications of recently developed military and telecommunications laser systems; (2) replace step-function discontinuities in the IR limits by continuously varying analytical functions of wavelength and pulsewidth which more closely follow the trends of the experimental retinal (for point-source laser exposures) and corneal ED50 threshold data; and (3) result in an overall simplification of the permissible exposure limits over the wavelength range from 1.2-2.6 mum. A specific proposal for amending the IR maximum permissible exposure limits over this wavelength range is presented.

Corneal elastic anisotropy and hysteresis as a function of IOP assessed by optical coherence elastography

NASA Astrophysics Data System (ADS)

Li, Jiasong; Singh, Manmohan; Han, Zhaolong; Wu, Chen; Raghunathan, Raksha; Liu, Chih-Hao; Nair, Achuth; Noorani, Shezaan; Aglyamov, Salavat R.; Twa, Michael D.; Larin, Kirill V.

2016-03-01

The mechanical anisotropic properties of the cornea can be an important indicator for determining the onset and severity of different diseases and can be used to assess the efficacy of various therapeutic interventions, such as cross-linking and LASIK surgery. In this work, we introduce a noncontact method of assessing corneal mechanical anisotropy as a function of intraocular pressure (IOP) using optical coherence elastography (OCE). A focused air-pulse induced low amplitude (<10 μm) elastic waves in fresh porcine corneas in the whole eye-globe configuration in situ. A phase-stabilized swept source optical coherence elastography (PhS-SSOCE) system imaged the elastic wave propagation at stepped radial angles, and the OCE measurements were repeated as the IOP was cycled. The elastic wave velocity was then quantified to determine the mechanical anisotropy and hysteresis of the cornea. The results show that the elastic anisotropy at the corneal of the apex of the cornea becomes more pronounced at higher IOPs, and that there are distinct radial angles of higher and lower stiffness. Due to the noncontact nature and small amplitude of the elastic wave, this method may be useful for characterizing the elastic anisotropy of ocular and other tissues in vivo completely noninvasively.

Primary cilia maintain corneal epithelial homeostasis by regulation of the Notch signaling pathway

PubMed Central

Grisanti, Laura; Revenkova, Ekaterina; Gordon, Ronald E.

2016-01-01

Primary cilia have been linked to signaling pathways involved in cell proliferation, cell motility and cell polarity. Defects in ciliary function result in developmental abnormalities and multiple ciliopathies. Patients affected by severe ciliopathies, such as Meckel syndrome, present several ocular surface disease conditions of unclear pathogenesis. Here, we show that primary cilia are predominantly present on basal cells of the mouse corneal epithelium (CE) throughout development and in the adult. Conditional ablation of cilia in the CE leads to an increase in proliferation and vertical migration of basal corneal epithelial cells (CECs). A consequent increase in cell density of suprabasal layers results in a thicker than normal CE. Surprisingly, in cilia-deficient CE, cilia-mediated signaling pathways, including Hh and Wnt pathways, were not affected but the intensity of Notch signaling was severely diminished. Although Notch1 and Notch2 receptors were expressed normally, nuclear Notch1 intracellular domain (N1ICD) expression was severely reduced. Postnatal development analysis revealed that in cilia-deficient CECs downregulation of the Notch pathway precedes cell proliferation defects. Thus, we have uncovered a function of the primary cilium in maintaining homeostasis of the CE by balancing proliferation and vertical migration of basal CECs through modulation of Notch signaling. PMID:27122169

Contact lens overrefraction variability in corneal power estimation after refractive surgery.

PubMed

Joslin, Charlotte E; Koster, James; Tu, Elmer Y

2005-12-01

To evaluate the accuracy and precision of the contact lens overrefraction (CLO) method in determining corneal refractive power in post-refractive-surgery eyes. Refractive Surgery Service and Contact Lens Service, University of Illinois, Chicago, Illinois, USA. Fourteen eyes of 7 subjects who had a single myopic laser in situ keratomileusis procedure within 12 months with refractive stability were included in this prospective case series. The CLO method was compared with the historical method of predicting the corneal power using 4 different lens fitting strategies and 3 refractive pupil scan sizes (3 mm, 5 mm, and total pupil). Rigid lenses included 3 9.0 mm overall diameter lenses fit flat, steep, and an average of the 2, and a 15.0 mm diameter lens steep fit. Cycloplegic CLO was performed using the autorefractor function of the Nidek OPD-Scan ARK-10000. Results with each strategy were compared with the corneal power estimated with the historical method. The bias (mean of the difference), 95% limits of agreement, and difference versus mean plots for each strategy are presented. In each subject, the CLO-estimated corneal power varied based on lens fit. On average, the bias between CLO and historical methods ranged from -0.38 to +2.42 diopters (D) and was significantly different from 0 in all but 3 strategies. Substantial variability in precision existed between fitting strategies, with the range of the 95% limits of agreement approximating 0.50 D in 2 strategies and 2.59 D in the worst-case scenario. The least precise fitting strategy was use of flat-fitting 9.0 mm diameter lenses. The accuracy and precision of the CLO method of estimating corneal power in post-refractive-surgery eyes was highly variable on the basis of how rigid lense were fit. One of the most commonly used fitting strategies in clinical practice--flat-fitting a 9.0 diameter lens-resulted in the poorest accuracy and precision. Results also suggest use of large-diameter lenses may improve outcomes.

Lactate-H+ Transport Is a Significant Component of the In Vivo Corneal Endothelial Pump

PubMed Central

Nguyen, Tracy T.; Bonanno, Joseph A.

2012-01-01

Purpose. To confirm the expression of monocarboxylate transporters (MCT) 1, 2, and 4 in rabbit CE and to test the hypothesis that cellular buffering contributed by HCO3−, NBCe1, and carbonic anhydrase (CA) activity facilitates lactate-H+ efflux thereby controlling corneal hydration in vivo. Methods. MCT1–4 expression of rabbit endothelium was examined by Western blotting and immunofluorescence staining. Lactate-induced acidification (LIA) was measured in perfused CE in the presence and absence of HCO3− and acetazolamide (ACTZ) using tissue treated with siRNA specific to MCT1, 2, and 4. Corneal thickness and lactate concentration were measured in New Zealand White rabbits treated with the topical CA inhibitor Azopt, and from eyes that were injected intracamerally with ouabain, disodium 4,4′-diisothiocyanatostilbene-2,2′-disulfonate (DIDS), and shRNA specific to the 1Na+:2HCO3− cotransporter NBCe1. Results. MCT1 and MCT4 are localized to the lateral membrane, while MCT2 is apical. Cell pH measurements showed LIA in response to 40 mM lactate in bicarbonate free (BF) Ringer's that was inhibited by niflumic acid and by MCT siRNA knockdown, and significantly reduced in the presence of HCO3−. Lactate-dependent proton flux in vitro was not significantly greater in the presence of HCO3− or reduced by ACTZ. However, when active transport, NBCe1, or CA activity was disrupted in vivo, corneal edema ensued and was associated with significant corneal lactate accumulation. Conclusions. MCT1, 2, and 4 are expressed in rabbit CE on both the apical and basolateral surfaces and function to transport lactate-H+. Lactate-H+ flux is facilitated by active transport, HCO3− transport and CA activity, disruption of which causes corneal edema in vivo and indicates that facilitation of lactate efflux is a component of the endothelial pump. PMID:22410572

[Biological characteristics of an enteroinvasive Escherichia coli strain with tatABC deletion].

PubMed

Gong, Zhaolong; Ye, Changyun; Liu, Xiaobing; Zhang, Min; Zhuo, Qin

2013-05-04

To study the relationship between twin-arginine translocation system (Tat) system with the biological characteristics of enteroinvasive Escherichia coli (EIEC). Through homologous recombination, we constructed EIEC's tatABC gene deletion strain and complementary strain, and explored their impact on bacterial form, substrate transport function as well as on HeLa cells and guinea pig's corneal invasion force. The tatABC gene deletion strain had apparent changes in bacterial form, loss of substrate transporter function, and significant weakened bacterial invasion force (the number of the deletion strain invading into HeLa cells was decreased significantly, and the ability of its corneal lesion capacity of the guinea pig was significantly weakened), while the complementary strain was similar to the wild strain in the above respects. EIEC's Tat protein transport system is closely related with the biological characteristics of EIEC.

Ocular surface immunity: homeostatic mechanisms and their disruption in dry eye disease.

PubMed

Barabino, Stefano; Chen, Yihe; Chauhan, Sunil; Dana, Reza

2012-05-01

The tear film, lacrimal glands, corneal and conjunctival epithelia and Meibomian glands work together as a lacrimal functional unit (LFU) to preserve the integrity and function of the ocular surface. The integrity of this unit is necessary for the health and normal function of the eye and visual system. Nervous connections and systemic hormones are well known factors that maintain the homeostasis of the ocular surface. They control the response to internal and external stimuli. Our and others' studies show that immunological mechanisms also play a pivotal role in regulating the ocular surface environment. Our studies demonstrate how anti-inflammatory factors such as the expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in corneal cells, immature corneal resident antigen-presenting cells, and regulatory T cells play an active role in protecting the ocular surface. Dry eye disease (DED) affects millions of people worldwide and negatively influences the quality of life for patients. In its most severe forms, DED may lead to blindness. The etiology and pathogenesis of DED remain largely unclear. Nonetheless, in this review we summarize the role of the disruption of afferent and efferent immunoregulatory mechanisms that are responsible for the chronicity of the disease, its symptoms, and its clinical signs. We illustrate current anti-inflammatory treatments for DED and propose that prevention of the disruption of immunoregulatory mechanisms may represent a promising therapeutic strategy towards controlling ocular surface inflammation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ocular Surface Immunity: Homeostatic Mechanisms and Their Disruption in Dry Eye Disease

PubMed Central

Barabino, Stefano; Chen, Yihe; Chauhan, Sunil; Dana, Reza

2012-01-01

The tear film, lacrimal glands, corneal and conjunctival epithelia and Meibomian glands work together as a lacrimal functional unit (LFU) to preserve the integrity and function of the ocular surface. The integrity of this unit is necessary for the health and normal function of the eye and visual system. Nervous connections and systemic hormones are well known factors that maintain the homeostasis of the ocular surface. They control the response to internal and external stimuli. Our and others’ studies show that immunological mechanisms also play a pivotal role in regulating the ocular surface environment. Our studies demonstrate how anti-inflammatory factors such as the expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in corneal cells, immature corneal resident antigen-presenting cells, and regulatory T cells play an active role in protecting the ocular surface. Dry eye disease (DED) affects millions of people worldwide and negatively influences the quality of life for patients. In its most severe forms, DED may lead to blindness. The etiology and pathogenesis of DED remain largely unclear. Nonetheless, in this review we summarize the role of the disruption of afferent and efferent immunoregulatory mechanisms that are responsible for the chronicity of the disease, its symptoms, and its clinical signs. We illustrate current anti-inflammatory treatments for DED and propose that prevention of the disruption of immunoregulatory mechanisms may represent a promising therapeutic strategy towards controlling ocular surface inflammation. PMID:22426080

Controlled-Release Personal Use Arthropod Repellent Formulation. Phase 2

DTIC Science & Technology

1986-09-15

damage, pitting M - Hypopyon N - Corneal neovascularization P - Pannus R - Unable to visualize due to severe opacity S - Granulation scar tissue POS...M - Hypopyon N - Corneal neovascularization P - Pannus R - Unable to visualize due to severe opacity S - Granulation scar tissue POS -Positive...Corneal epithelial damage, piling L - Corneal epithelial damage, pitting M - Hypopyon N - Corneal neovascularization P - Pannus R - Unable to

[Followup of chicken pox keratitis. Anatomic-clinical case report].

PubMed

D'hermies, F; Ellies, P; Meyer, A; Halhal, M; Morel, X; Behar-Cohen, F; Renard, G; Dighiero, P

2002-09-01

Chicken pox is a very common infectious disease in children. Its corneal involvement is less serious than with measles, which may lead to blindness in numerous developing countries. However, with occasional cases occur. A case of a 59-year-old male patient whose left cornea was involved during a chicken pox infection at the age of 7 is reported. More recently, the vision of the right eye was normal at 20/20 and reduced to visual perception in the affected left eye. Corneal sensitivity was maintained in the left eye, which, however exhibited a central epithelial defect. A central round opacity of the left corneal stroma was believed to be the scar resulting from a previous disciform keratitis. The left central cornea was thinned and there was neither an anterior chamber flare nor new corneal vessels. This corneal condition required a corneal allograft, performed quickly because of the potential risk of perforation. Histopathological study of the corneal button showed a central corneal thinning with an increase in epithelial thickness. The corneal stroma was disorganized, with irregular collagen bundles. No inflammatory cells could be observed, however. All the histopathological changes observed were those of a corneal scar.

Morphological Changes of Human Corneal Endothelial Cells after Rho-Associated Kinase Inhibitor Eye Drop (Ripasudil) Administration: A Prospective Open-Label Clinical Study

PubMed Central

Okumura, Naoki; Suganami, Hideki; Kinoshita, Shigeru

2015-01-01

Purpose To investigate the effect and safety of a selective Rho kinase inhibitor, ripasudil 0.4% eye drops, on corneal endothelial cells of healthy subjects. Design Prospective, interventional case series. Methods In this study, 6 healthy subjects were administered ripasudil 0.4% in the right eye twice daily for 1 week. Morphological changes and corneal endothelial cell density were examined by noncontact and contact specular microscopy. Central corneal thickness and corneal volume of 5 mm-diameter area of center cornea were analyzed by Pentacam Scheimpflug topography. All the above measurements were conducted in both eyes before administration, 1.5 and 6 hours after the initial administration on day 0; and in the same manner after the final administration on day 7. Results By noncontact specular microscopy, indistinct cell borders with pseudo guttae were observed, but by contact specular microscopy, morphological changes of corneal endothelial cells were mild and pseudo guttae was not observed after single and repeated administration of ripasudil in all subjects. These changes resolved prior to the next administration, and corneal endothelial cell density, central corneal thickness and corneal volume were not changed throughout the study period. Conclusion Transient morphological changes of corneal endothelial cells such as indistinct cell borders with pseudo guttae were observed by noncontact specular microscopy in healthy subjects after ripasudil administration. Corneal edema was not observed and corneal endothelial cell density did not decrease after 1 week repetitive administration. These morphological changes were reversible and corneal endothelial cell morphology returned to normal prior to the next administration. Trial Registration JAPIC Clinical Trials Information 142705 PMID:26367375

Correlation between apical protrusion in the Scheimflug imaging and Corneal Hysteresis and Corneal Resistance factor by Ocular Response Analyzer, among refractive non-keratoconic Egyptian patients.

PubMed

Refai, Tamer Adel

2015-10-01

Apical protrusion in the central 4-mm ring in the Scheimflug imaging (Pentacam), both for the anterior and posterior floats as well as Corneal Hysteresis and Corneal Resistance Factor by Ocular Response Analyzer (ORA), generally are considered important predictors for post-Lasik ectasia. The aim of this work was to find out if there is a statistically significant correlation between these different predictors and their correlation with the central corneal thickness for refractive non-keratoconic Egyptian patients trying to achieve a better decision and avoiding ectasia. This case-control study involved 142 eyes (of 77 patients with various refractive errors) arriving at the refractive surgery unit in the Research Institute of Ophthalmology in Giza (Egypt) in 2014-2015 seeking excimer laser ablation. The flattest, steepest keratometry readings, central corneal thickness as well as the apical protrusion in the central 4-mm ring, both for the anterior and posterior floats, in microns were measured by Scheimflug imaging. The Corneal Hysteresis and Corneal Resistance Factor were measured by the ocular response analyzer. Statistical analysis was performed by SPSS, using the Pearson correlation test. The spherical refractive error ranged from +7.00 to -13.00 diopters (-3.80 ± 2.89). The central pachymetry ranged from 494 to 634 μm (550.35 ± 32.13). For the central 4-mm ring, the apical protrusion ranged from 0 to +15 μ (6.93 ± 2.99) for the anterior float and from -3 to +20 μ (9.33 ± 4.55) for the posterior float. The Corneal Hysterisis (CH) ranged from 7 to 14.8 mmHg (10.18±1.44), while the Corneal Resistance Factor (CRF) ranged from 7.5 to 14.9 mmHg (10.58 ± 1.67). There was a strong positive correlation between the central corneal thickness and both Corneal Hysteresis (CH: r = 0.56, P ≤ 0.01) and Corneal Resistance Factor (r = 0.46, P ≤ 0.01). A significant correlation (P < 0.05, r = 0.15) existed between apical protrusion in the posterior float and the central corneal thickness. Also, significant negative correlation (P < 0.05, r = -0.12) existed between apical protrusion in the anterior float by pentacam and the Corneal Resistance Factor by ocular response analyzer. Our finding of a strong positive correlation between both Corneal Hysteresis and Corneal Resistance Factor and the Central corneal thickness being important for biomechanical corneal stability. The findings of this study also support using both machines preoperatively to decrease the risk of post-Lasik ectasia.

Electrospun nanofibrous SF/P(LLA-CL) membrane: a potential substratum for endothelial keratoplasty.

PubMed

Chen, Junzhao; Yan, Chenxi; Zhu, Mengyu; Yao, Qinke; Shao, Chunyi; Lu, Wenjuan; Wang, Jing; Mo, Xiumei; Gu, Ping; Fu, Yao; Fan, Xianqun

2015-01-01

Cornea transplant technology has progressed markedly in recent decades, allowing surgeons to replace diseased corneal endothelium by a thin lamellar structure. A thin, transparent, biocompatible, tissue-engineered substratum with corneal endothelial cells for endothelial keratoplasty is currently of interest. Electrospinning a nanofibrous structure can simulate the extracellular matrix and have beneficial effects for cell culture. Silk fibroin (SF) has good biocompatibility but poor mechanical properties, while poly(L-lactic acid-co-ε-caprolactone) (P(LLA-CL)) has good mechanical properties but poor biocompatibility. Blending SF with P(LLA-CL) can maintain the advantages of both these materials and overcome their disadvantages. Blended electrospun nanofibrous membranes may be suitable for regeneration of the corneal endothelium. The aim of this study was to produce a tissue-engineered construct suitable for endothelial keratoplasty. Five scaffolds containing different SF:P(LLA-CL) blended ratios (100:0, 75:25, 50:50, 25:75, 0:100) were manufactured. A human corneal endothelial (B4G12) cell line was cultured on the membranes. Light transmission, speed of cell adherence, cell viability (live-dead test), cell proliferation (Ki-67, BrdU staining), and cell monolayer formation were detected on membranes with the different blended ratios, and expression of some functional genes was also detected by real-time polymerase chain reaction. Different blended ratios of scaffolds had different light transmittance properties. The 25:75 blended ratio membrane had the best transmittance among these scaffolds. All electrospun nanofibrous membranes showed improved speed of cell adherence when compared with the control group, especially when the P(LLA-CL) ratio increased. The 25:75 blended ratio membranes also had the highest cell proliferation. B4G12 cells could form a monolayer on all scaffolds, and most functional genes were also stably expressed on all scaffolds. Only two genes showed changes in expression. All blended ratios of SF:P(LLA-CL) scaffolds were evaluated and showed good biocompatibility for cell adherence and monolayer formation. Among them, the 25:75 blended ratio SF:P(LLA-CL) scaffold had the best transmittance and the highest cell proliferation. These attributes further the potential application of the SF:P(LLA-CL) scaffold for corneal endothelial transplantation.

Characteristics of astigmatism as a function of age in a Hong Kong clinical population.

PubMed

Leung, Tsz-Wing; Lam, Andrew Kwok-Cheung; Deng, Li; Kee, Chea-Su

2012-07-01

To characterize astigmatism as a function of age in a Hong Kong clinical population. All records from new clinical patients at a university optometry clinic in the year 2007 were used for the study. Only data from subjects with corrected visual acuity ≥6/9 in both eyes and with completed subjective refraction were analyzed. The subjects were divided into seven age groups by decade (i.e., 3 to 10 years, 11 to 20 years, …, >60 years). Refractive errors were decomposed into spherical-equivalent refractive error (M), J0, and J45 astigmatic components for analyses. Internal astigmatism was calculated by subtracting corneal astigmatism from refractive astigmatism (RA). Of the 2759 cases that fulfilled our selection criteria, 58.9% had myopia (M ≥-0.75 D) and 28.4% had RA (Cyl ≥ 1.00 D). The prevalence of RA increased from 17.8% in the 3 to 10 years age group to 38.1% in the 21 to 30 years age group. It then dipped to 25.8% in 41 to 50 years age group but increased again to 41.8% in the >60 years age group. Among the astigmats, almost all 3- to 10-year-old children (92.6%) had with-the-rule (WTR) astigmatism, but a majority of the elderly (>60 years) had against-the-rule (ATR) astigmatism (79.7%). For a subset of subjects who had both subjective refraction and keratometric readings (n = 883), RA was more strongly correlated with corneal (r = 0.35 to 0.74) than with internal astigmatism (r = 0.01 to 0.35). More importantly, the magnitudes of both refractive and corneal J0 were consistent with synchronized decrements (-0.15 and -0.14 D per 10 years, respectively) after the age of 30 years, indicating that the shift toward more ATR astigmatism was related to corneal change. In this Hong Kong Chinese clinical population, the prevalence rates of both myopia and astigmatism increased during the first three decades and shared a similar trend before the age of 50 years. The manifest astigmatism was mainly corneal in nature, bilaterally mirror symmetric in axis, and shifted from predominantly WTR to ATR with age.

Ion Transport Function of SLC4A11 in Corneal Endothelium

PubMed Central

Jalimarada, Supriya S.; Ogando, Diego G.; Vithana, Eranga N.; Bonanno, Joseph A.

2013-01-01

Purpose. Mutations in SLC4A11, a member of the SLC4 superfamily of bicarbonate transporters, give rise to corneal endothelial cell dystrophies. SLC4A11 is a putative Na+ borate and Na+:OH− transporter. Therefore we ask whether SLC4A11 in corneal endothelium transports borate (B[OH]4−), bicarbonate (HCO3−), or hydroxyl (OH−) anions coupled to Na+. Methods. SLC4A11 expression in cultured primary bovine corneal endothelial cells (BCECs) was determined by semiquantitative PCR, SDS-PAGE/Western blotting, and immunofluorescence staining. Ion transport function was examined by measuring intracellular pH (pHi) or Na+ ([Na+]i) in response to Ringer solutions with/without B(OH)4− or HCO3− after overexpressing or small interfering RNA (siRNA) silencing of SLC4A11. Results. SLC4A11 is localized to the basolateral membrane in BCEC. B(OH)4− (2.5–10 mM) in bicarbonate-free Ringer induced a rapid small acidification (0.01 pH unit) followed by alkalinization (0.05–0.1 pH unit), consistent with diffusion of boric acid into the cell followed by B(OH)4−. However, the rate of B(OH)4−-induced pHi change was unaffected by overexpression of SLC4A11. B(OH)4− did not induce significant changes in resting [Na+i] or the amplitude and rate of acidification caused by Na+ removal. siRNA-mediated knockdown of SLC4A11 (∼70%) did not alter pHi responses to CO2/HCO3−-rich Ringer, Na+-free induced acidification, or the rate of Na+ influx in the presence of bicarbonate. However, in the absence of bicarbonate, siSLC4A11 knockdown significantly decreased the rate (43%) and amplitude (48%) of acidification due to Na+ removal and recovery (53%) upon add-back. Additionally, the rate of acid recovery following NH4+ prepulse was decreased significantly (27%) by SLC4A11 silencing. Conclusions. In corneal endothelium, SLC4A11 displays robust Na+-coupled OH− transport, but does not transport B(OH)4− or HCO3−. PMID:23745003

Collagen Cross-Linking Using Riboflavin and Ultraviolet-A for Corneal Thinning Disorders

PubMed Central

Pron, G; Ieraci, L; Kaulback, K

2011-01-01

Executive Summary Objective The main objectives for this evidence-based analysis were to determine the safety and effectiveness of photochemical corneal collagen cross-linking with riboflavin (vitamin B2) and ultraviolet-A radiation, referred to as CXL, for the management of corneal thinning disease conditions. The comparative safety and effectiveness of corneal cross-linking with other minimally invasive treatments such as intrastromal corneal rings was also reviewed. The Medical Advisory Secretariat (MAS) evidence-based analysis was performed to support public financing decisions. Subject of the Evidence-Based Analysis The primary treatment objective for corneal cross-linking is to increase the strength of the corneal stroma, thereby stabilizing the underlying disease process. At the present time, it is the only procedure that treats the underlying disease condition. The proposed advantages for corneal cross-linking are that the procedure is minimally invasive, safe and effective, and it can potentially delay or defer the need for a corneal transplant. In addition, corneal cross-linking does not adversely affect subsequent surgical approaches, if they are necessary, or interfere with corneal transplants. The evidence for these claims for corneal cross-linking in the management of corneal thinning disorders such as keratoconus will be the focus of this review. The specific research questions for the evidence review were as follows: Technical: How technically demanding is corneal cross-linking and what are the operative risks? Safety: What is known about the broader safety profile of corneal cross-linking? Effectiveness - Corneal Surface Topographic Affects: What are the corneal surface remodeling effects of corneal cross-linking? Do these changes interfere with subsequent interventions, particularly corneal transplant known as penetrating keratoplasty (PKP)? Effectiveness -Visual Acuity: What impacts does the remodeling have on visual acuity? Are these impacts predictable, stable, adjustable and durable? Effectiveness - Refractive Outcomes: What impact does remodeling have on refractive outcomes? Effectiveness - Visual Quality (Symptoms): What impact does corneal cross-linking have on vision quality such as contrast vision, and decreased visual symptoms (halos, fluctuating vision)? Effectiveness - Contact lens tolerance: To what extent does contact lens intolerance improve after corneal cross-linking? Vision-Related QOL: What is the impact of corneal cross-linking on functional visual rehabilitation and quality of life? Patient satisfaction: Are patients satisfied with their vision following the procedure? Disease Process: What impact does corneal cross-linking have on the underling corneal thinning disease process? Does corneal cross-linking delay or defer the need for a corneal transplant? What is the comparative safety and effectiveness of corneal cross-linking compared with other minimally invasive treatments for corneal ectasia such as intrastromal corneal rings? Clinical Need: Target Population and Condition Corneal ectasia (thinning) disorders represent a range of disorders involving either primary disease conditions, such as keratoconus (KC) and pellucid marginal corneal degeneration, or secondary iatrogenic conditions, such as corneal thinning occurring after laser in situ keratomileusis (LASIK) refractive surgery. Corneal thinning is a disease that occurs when the normally round dome-shaped cornea progressively thins causing a cone-like bulge or forward protrusion in response to the normal pressure of the eye. The thinning occurs primarily in the stroma layers and is believed to be a breakdown in the collagen process. This bulging can lead to irregular astigmatism or shape of the cornea. Because the anterior part of the cornea is responsible for most of the focusing of the light on the retina, this can then result in loss of visual acuity. The reduced visual acuity can make even simple daily tasks, such as driving, watching television or reading, difficult to perform. Keratoconus is the most common form of corneal thinning disorder and involves a noninflammatory chronic disease process of progressive corneal thinning. Although the specific cause for the biomechanical alterations in the corneal stroma is unknown, there is a growing body of evidence suggesting that genetic factors may play an important role. Keratoconus is a rare disease (< 0.05% of the population) and is unique among chronic eye diseases because it has an early onset, with a median age of 25 years. Disease management for this condition follows a step-wise approach depending on disease severity. Contact lenses are the primary treatment of choice when there is irregular astigmatism associated with the disease. Patients are referred for corneal transplants as a last option when they can no longer tolerate contact lenses or when lenses no longer provide adequate vision. Keratoconus is one of the leading indications for corneal transplants and has been so for the last 3 decades. Despite the high success rate of corneal transplants (up to 20 years) there are reasons to defer it as long as possible. Patients with keratoconus are generally young and a longer-term graft survival of at least 30 or 40 years may be necessary. The surgery itself involves lengthy time off work and postsurgery, while potential complications include long-term steroid use, secondary cataracts, and glaucoma. After a corneal transplant, keratoconus may recur resulting in a need for subsequent interventions. Residual refractive errors and astigmatism can remain challenges after transplantation, and high refractive surgery and regraft rates in KC patients have been reported. Visual rehabilitation or recovery of visual acuity after transplant may be slow and/or unsatisfactory to patients. Description of Technology/Therapy Corneal cross-linking involves the use of riboflavin (vitamin B2) and ultraviolet-A (UVA) radiation. A UVA irradiation device known as the CXL® device (license number 77989) by ACCUTECH Medical Technologies Inc. has been licensed by Health Canada as a Class II device since September 19, 2008. An illumination device that emits homogeneous UVA, in combination with any generic form of riboflavin, is licensed by Health Canada for the indication to slow or stop the progression of corneal thinning caused by progressive keratectasia, iatrogenic keratectasia after laser-assisted in situ keratomileusis (LASIK) and pellucid marginal degeneration. The same device is named the UV-X® device by IROCMedical, with approvals in Argentina, the European Union and Australia. UVA devices all use light emitting diodes to generate UVA at a wavelength of 360-380 microns but vary in the number of diodes (5 to 25), focusing systems, working distance, beam diameter, beam uniformity and extent to which the operator can vary the parameters. In Ontario, CXL is currently offered at over 15 private eye clinics by refractive surgeons and ophthalmologists. The treatment is an outpatient procedure generally performed with topical anesthesia. The treatment consists of several well defined procedures. The epithelial cell layer is first removed, often using a blunt spatula in a 9.0 mm diameter under sterile conditions. This step is followed by the application of topical 0.1% riboflavin (vitamin B2) solution every 3 to 5 minutes for 25 minutes to ensure that the corneal stroma is fully penetrated. A solid-state UVA light source with a wavelength of 370 nm (maximum absorption of riboflavin) and an irradiance of 3 mW/cm2 is used to irradiate the central cornea. Following treatment, a soft bandage lens is applied and prescriptions are given for oral pain medications, preservative-free tears, anti-inflammatory drops (preferably not nonsteroidal anti-inflammatory drugs, or NSAIDs) and antibiotic eye drops. Patients are recalled 1 week following the procedure to evaluate re-epithelialization and they are followed-up subsequently. Evidence-Based Analysis Methods A literature search was conducted on photochemical corneal collagen cross-linking with riboflavin (vitamin B2) and ultraviolet-A for the management of corneal thinning disorders using a search strategy with appropriate keywords and subject headings for CXL for literature published up until April 17, 2011. The literature search for this Health Technology Assessment (HTA) review was performed using the Cochrane Library, the Emergency Care Research Institute (ECRI) and the Centre for Reviews and Dissemination. The websites of several other health technology agencies were also reviewed, including the Canadian Agency for Drugs and Technologies in Health (CADTH) and the United Kingdom’s National Institute for Clinical Excellence (NICE). The databases searched included OVID MEDLINE, MEDLINE IN-Process and other Non-Indexed Citations such as EMBASE. As the evidence review included an intervention for a rare condition, case series and case reports, particularly for complications and adverse events, were reviewed. A total of 316 citations were identified and all abstracts were reviewed by a single reviewer for eligibility. For those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Inclusion Criteria English-language reports and human studies patients with any corneal thinning disorder reports with CXL procedures used alone or in conjunction with other interventions original reports with defined study methodology reports including standardized measurements on outcome events such as technical success, safety effectiveness, durability, vision quality of life or patient satisfaction systematic reviews, meta-analyses, randomized controlled trials, observational studies, retrospective analyses, case series, or case reports for complications and adverse events Exclusion Criteria nonsystematic reviews, letters, comments and editorials reports not involving outcome events such as safety, effectiveness, durability, vision quality or patient satisfaction following an intervention with corneal implants reports not involving corneal thinning disorders and an intervention involving CXL Summary of Evidence Findings In the Medical Advisory Secretariat evidence review on corneal cross-linking, 65 reports (16 case reports) involving 1403 patients were identified on the use of CXL for managing corneal thinning disorders. The reports were summarized according to their primary clinical indication, whether or not secondary interventions were used in conjunction with CXL (referred to as CXL-Plus) and whether or not it was a safety-related report. The safety review was based on information from the cohort studies evaluating effectiveness, clinical studies evaluating safety, treatment response or recovery, and published case reports of complications. Complications, such as infection and noninfectious keratitis (inflammatory response), reported in case reports, generally occurred in the first week and were successfully treated with topical antibiotics and steroids. Other complications, such as the cytotoxic effects on the targeted corneal stroma, occurred as side effects of the photo-oxidative process generated by riboflavin and ultraviolet-A and were usually reversible. The reports on treatment effectiveness involved 15 pre-post longitudinal cohort follow-up studies ranging from follow-up of patients’ treated eye only, follow-up in both the treated and untreated fellow-eye; and follow-up in the treated eye only and a control group not receiving treatment. One study was a 3-arm randomized control study (RCT) involving 2 comparators: one comparator was a sham treatment in which one eye was treated with riboflavin only; and the other comparator was the untreated fellow-eye. The outcomes reported across the studies involved statistically significant and clinically relevant improvements in corneal topography and refraction after CXL. In addition, improvements in treated eyes were accompanied by worsening outcomes in the untreated fellow-eyes. Improvements in corneal topography reported at 6 months were maintained at 1- and 2-year follow-up. Visual acuity, although not always improved, was infrequently reported as vision loss. Additional procedures such as the use of intrastromal corneal ring segments, intraocular lenses and refractive surgical practices were reported to result in additional improvements in topography and visual acuity after CXL. Considerations for Ontario Health System The total costs of providing CXL therapy to keratoconus patients in Ontario was calculated based on estimated physician, clinic, and medication costs. The total cost per patient was approximately $1,036 for the treatment of one eye, and $1,751 for the treatment of both eyes. The prevalence of keratoconus was estimated at 4,047 patients in FY2011, with an anticipated annual incidence (new cases) of about 148 cases. After distributing the costs of CXL therapy for the FY2011 prevalent keratoconus population over the next 3 years, the estimated average annual cost was approximately $2.1 million, of which about $1.3 million would be physician costs specifically. Conclusion Corneal cross-linking effectively stabilizes the underlying disease, and in some cases reverses disease progression as measured by key corneal topographic measures. The affects of CXL on visual acuity are less predictable and the use of adjunct interventions with CXL, such as intrastromal corneal ring segments, refractive surgery, and intraocular lens implants are increasingly employed to both stabilize disease and restore visual acuity. Although the use of adjunct interventions have been shown to result in additional clinical benefit, the order, timing, and risks of performing adjunctive interventions have not been well established. Although there is potential for serious adverse events with corneal UVA irradiation and photochemical reactions, there have been few reported complications. Those that have occurred tended to be related to side effects of the induced photochemical reactions and were generally reversible. However, to ensure that there are minimal complications with the use of CXL and irradiation, strict adherence to defined CXL procedural protocols is essential. Keywords Keratoconus, corneal cross-linking, corneal topography, corneal transplant, visual acuity, refractive error. PMID:23074417

[The relations of corneal, lenticular and total astigmatism].

PubMed

Liang, D; Guan, Z; Lin, J

1995-06-01

To determine the relations of corneal, lenticular and total astigmatism and the changes of the astigmatism with age. Out-patients with refractive errors were refracted with retinoscope after using cycloplegic drops and measured the radii of anterior corneal curvature. One hundred and ninety-four cases (382 eyes) with refractive errors were studied. Of the eyes 67.9% had regular corneal astigmatism, 68.1% irregular lenticular astigmatism and 60.7% regular total astigmatism, 88.5% of the corneal astigmatism has the same quality as the total astigmatism. The total astigmatism in 46% of the eyes included the summation of corneal and lenticular astigmatism, but in 41.3% of the eyes irregular lenticular astigmatism corrected the regular corneal astigmatism. The astigmatism of cornea, lens and total astigmatism changed from regular to irregular with the increase of age. The linear correlation analysis showed a positive correlation between the power of horizontal corneal refraction and age, and a negative corrlation between the power of vertical corneal refraction and age. The shape of cornea was the major cause of total astigmatism. The influence of lens on the total astigmatism was different. The reasons for the change of the total astigmatism from regular to irregular with the increase of age were the changes of the power of corneal refraction, particularly the increase of the power of horizontal corneal refraction and lenticular irregular astigmatism.

Corneal repair by human corneal keratocyte-reprogrammed iPSCs and amphiphatic carboxymethyl-hexanoyl chitosan hydrogel.

PubMed

Chien, Yueh; Liao, Yi-Wen; Liu, Dean-Mo; Lin, Heng-Liang; Chen, Shih-Jen; Chen, Hen-Li; Peng, Chi-Hsien; Liang, Chang-Min; Mou, Chung-Yuan; Chiou, Shih-Hwa

2012-11-01

Induced pluripotent stem cells (iPSCs) have promising potential in regenerative medicine, but whether iPSCs can promote corneal reconstruction remains undetermined. In this study, we successfully reprogrammed human corneal keratocytes into iPSCs. To prevent feeder cell contamination, these iPSCs were cultured onto a serum- and feeder-free system in which they remained stable through 30 passages and showed ESC-like pluripotent property. To investigate the availability of iPSCs as bioengineered substitutes in corneal repair, we developed a thermo-gelling injectable amphiphatic carboxymethyl-hexanoyl chitosan (CHC) nanoscale hydrogel and found that such gel increased the viability and CD44+proportion of iPSCs, and maintained their stem-cell like gene expression, in the presence of culture media. Combined treatment of iPSC with CHC hydrogel (iPSC/CHC hydrogel) facilitated wound healing in surgical abrasion-injured corneas. In severe corneal damage induced by alkaline, iPSC/CHC hydrogel enhanced corneal reconstruction by downregulating oxidative stress and recruiting endogenous epithelial cells to restore corneal epithelial thickness. Therefore, we demonstrated that these human keratocyte-reprogrammed iPSCs, when combined with CHC hydrogel, can be used as a rapid delivery system to efficiently enhance corneal wound healing. In addition, iPSCs reprogrammed from corneal surgical residues may serve as an alternative cell source for personalized therapies for human corneal damage. Copyright © 2012 Elsevier Ltd. All rights reserved.

Osteo-odonto keratoprosthesis in Stevens-Johnson syndrome: a case report.

PubMed

Sc, Reddy; I, Tajunisah; T, Tan D

2011-01-01

To report a successful osteo-odonto keratoprosthesis (OOKP) procedure in a case of end stage of corneal blindness due to Stevens-Johnson syndrome (SJS). An interventional case report. We describe a 35-year-old Indian woman, a known case of SJS with bilateral dry eyes and corneal blindness (failed corneal graft with vascularised total corneal opacity in the right eye and non-healing corneal ulcer in the left eye). Vision was hand movement only in both eyes. The corneal ulcer healed with medical treatment resulting in vascularised total corneal opacity with no improvement in vision. OOKP was performed in the right eye and the vision was improved from hand movement to 6/6. The same vision was maintained in the right eye at the last follow-up 5 years after surgery. OOKP provides good visual rehabilitation with long-term anatomically stable prosthesis in patients with end-stage of ocular surface disorders and corneal blindness secondary to SJS.

History of corneal transplantation in Australia.

PubMed

Coster, Douglas J

2015-04-01

Corneal transplantation is a triumph of modern ophthalmology. The possibility of corneal transplantation was first raised in 1797 but a century passed before Zirm achieved the first successful penetrating graft in 1905. Gibson reported the first corneal graft in Australia from Brisbane in 1940 and English established the first eye bank there a few years later. Corneal transplantation evolved steadily over the twentieth century. In the second half of the century, developments in microsurgery, including surgical materials such as monofilament nylon and strong topical steroid drops, accounted for improvements in outcomes. In 2013, approximately 1500 corneal transplants were done in Australia. Eye banking has evolved to cope with the rising demands for donor corneas. Australian corneal surgeons collaborated to establish and support the Australian Corneal Graft Registry in 1985. It follows the outcomes of their surgery and has become an important international resource for surgeons seeking further improvement with the procedure. © 2014 Royal Australian and New Zealand College of Ophthalmologists.

Effect of Cycloplegia on Corneal Biometrics and Refractive State

PubMed Central

Bagheri, Abbas; Feizi, Mohadeseh; Shafii, Aliakbar; Faramarzi, Amir; Tavakoli, Mehdi; Yazdani, Shahin

2018-01-01

Purpose: To determine changes in refractive state and corneal parameters after cycloplegia with cyclopentolate hydrochloride 1% using a dual Scheimpflug imaging system. Methods: In this prospective cross-sectional study patients aged 10 to 40 years who were referred for optometric evaluation enrolled and underwent autorefraction and corneal imaging with the Galilei dual Scheimpflug system before and 30 minutes after twice instillation of medication. Changes in refraction and astigmatism were investigated. Corneal biometrics including anterior and posterior corneal curvatures, total corneal power and corneal pachymetry were compared before and after cycloplegia. Results: Two hundred and twelve eyes of 106 subjects with mean age of 28 ± 5 years including 201 myopic and 11 hyperopic eyes were evaluated. Mean spherical equivalent refractive error before cycloplegia was -3.4 ± 2.6 D. A mean hyperopic shift of 0.4 ± 0.5 D occurred after cycloplegia (P < 0.001). The astigmatism power did not significantly change (P = 0.8), however, 26.8% of eyes with significant astigmatism experienced a change of more than 5 degrees in the axis of astigmatism. Changes in posterior corneal curvature were scant but statistically significant (P = 0.001). Moreover, corneal thickness was slightly increased in the central and paracentral regions (P < 0.001 and P < 0.001, respectively). Conclusion: Cycloplegia causes a hyperopic shift and astigmatism axis changes, along with an increase in central and paracentral corneal thickness and change in posterior corneal curvature. The effects of cycloplegia on refraction and corneal biometrics should be considered before cataract and refractive surgeries. PMID:29719636

Corneal donor tissue preparation for endothelial keratoplasty.

PubMed

Woodward, Maria A; Titus, Michael; Mavin, Kyle; Shtein, Roni M

2012-06-12

Over the past ten years, corneal transplantation surgical techniques have undergone revolutionary changes. Since its inception, traditional full thickness corneal transplantation has been the treatment to restore sight in those limited by corneal disease. Some disadvantages to this approach include a high degree of post-operative astigmatism, lack of predictable refractive outcome, and disturbance to the ocular surface. The development of Descemet's stripping endothelial keratoplasty (DSEK), transplanting only the posterior corneal stroma, Descemet's membrane, and endothelium, has dramatically changed treatment of corneal endothelial disease. DSEK is performed through a smaller incision; this technique avoids 'open sky' surgery with its risk of hemorrhage or expulsion, decreases the incidence of postoperative wound dehiscence, reduces unpredictable refractive outcomes, and may decrease the rate of transplant rejection. Initially, cornea donor posterior lamellar dissection for DSEK was performed manually resulting in variable graft thickness and damage to the delicate corneal endothelial tissue during tissue processing. Automated lamellar dissection (Descemet's stripping automated endothelial keratoplasty, DSAEK) was developed to address these issues. Automated dissection utilizes the same technology as LASIK corneal flap creation with a mechanical microkeratome blade that helps to create uniform and thin tissue grafts for DSAEK surgery with minimal corneal endothelial cell loss in tissue processing. Eye banks have been providing full thickness corneas for surgical transplantation for many years. In 2006, eye banks began to develop methodologies for supplying precut corneal tissue for endothelial keratoplasty. With the input of corneal surgeons, eye banks have developed thorough protocols to safely and effectively prepare posterior lamellar tissue for DSAEK surgery. This can be performed preoperatively at the eye bank. Research shows no significant difference in terms of the quality of the tissue or patient outcomes using eye bank precut tissue versus surgeon-prepared tissue for DSAEK surgery. For most corneal surgeons, the availability of precut DSAEK corneal tissue saves time and money, and reduces the stress of performing the donor corneal dissection in the operating room. In part because of the ability of the eye banks to provide high quality posterior lamellar corneal in a timely manner, DSAEK has become the standard of care for surgical management of corneal endothelial disease. The procedure that we are describing is the preparation of the posterior lamellar cornea at the eye bank for transplantation in DSAEK surgery (Figure 1).

Lymphatic vessels correlate closely with inflammation index in alkali burned cornea.

PubMed

Yan, Hao; Qi, Chaoxiu; Ling, Shiqi; Li, Weihua; Liang, Linyi

2010-08-01

To study the relationship between corneal lymphangiogenesis and inflammation in alkali burned corneas. Rat corneal lymphatic and blood vessels were labeled and distinguished by whole mount immunofluorescence and 5'-nase-alkaline phosphatase (5'-NA-ALP) double enzyme-histochemistry. Then, lymphatic vessel areas (LVA) and lymphatic vessel counting (LVC) were examined. Corneal inflammation was evaluated by inflammation index (IF) grading, histopathology, electron microscope, and polymorphonuclear leukocyte (PMN) infiltration. The relationship between LVC, LVA, IF, and PMN was examined, respectively. In addition, corneal lymphatic vessels of eleven human alkali burned corneas were examined by lymphatic vessel endothelial receptor (LYVE-1) immunohistochemistry. Corneal lymphangiogenesis occurred on Day 3, reached the peak at the end of two weeks, and disappeared five weeks after alkaline burns. Both LVA and LVC were strongly and positively correlated with IF after corneal alkaline burns. However, the relationship between LVC and PMN, between LVA and PMN were significant but converse. Among eleven human alkali burned corneas, corneal lymphangiogenesis was present in three corneas. Corneal lymphagiogenesis develops after alkaline burns and correlates closely with corneal inflammation.

Corneal power, thickness, and stiffness: results of a prospective randomized controlled trial of PRK and LASIK for myopia.

PubMed

Hjortdal, Jesper Ø; Møller-Pedersen, Torben; Ivarsen, Anders; Ehlers, Niels

2005-01-01

To compare the short-, medium-, and long-term changes in corneal optical power and corneal aberrations, central corneal thickness, and corneal "stiffness" assessed by pneumotonometry readings in patients having laser in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK) for myopia. Department of Ophthalmology, Arhus University Hospital, Arhus, Denmark. One eye of each of 45 patients with myopia ranging from -6.00 to -8.00 diopters (D) (spherical equivalent spectacle refraction [SER]) was randomized to LASIK (n=25; mean SER -7.12 D +/- 0.57 [SD]) or PRK (n=20; mean SER -6.91 +/- 0.57 D). Data were collected prospectively before and 1, 3, 6, 12, and 36 months after surgery. Measurements included corneal topography (TMS-1, Tomey), corneal thickness (ultrasound pachymetry), and apparent intraocular pressure (IOP) (pneumotonometry). Retreatments were not performed during the first year, and retreated eyes were excluded from the 3-year follow-up. Changes in corneal power and aberrations, thickness, and apparent IOP were calculated in a pair-wise manner for 3 time periods: short term (preoperative to 1 month after surgery), medium term (1 to 12 months after surgery), and long term (1 to 3 years after surgery). In the short term, corneal power decreased equally in LASIK and PRK eyes. Spherical aberrations and coma-like aberrations increased equally, while corneal thickness decreased significantly less in LASIK eyes than in PRK eyes. The apparent IOP decreased more in LASIK eyes than in PRK eyes. In the medium term, corneal power increased significantly in both groups. Spherical aberrations decreased significantly in PRK eyes but not in LASIK eyes. From 1 to 12 months, corneal thickness increased more in PRK eyes than in LASIK eyes. During this period, the apparent IOP increased significantly in LASIK eyes. In the long term, corneal power and corneal aberrations did not change significantly in either group. Corneal thickness increased slightly but significantly in both groups. The apparent IOP increased significantly more in PRK eyes. Differences between LASIK and PRK related to time-dependent events affecting corneal shape and structural integrity were present. Peripheral changes in flap hydration in LASIK eyes and epithelial and/or stromal thickening in PRK eyes appeared to be the most important factors in optical power changes in the first year after treatment. The changes in apparent IOP suggest that some interlamellar healing occurred during the first year after LASIK. After LASIK and PRK, corneal bending stiffness seemed permanently decreased, although some restiffening may occur in PRK eyes in the long term.

Granular corneal dystrophy Groenouw type I (GrI) and Reis-Bücklers' corneal dystrophy (R-B). One entity?

PubMed

Møller, H U

1989-12-01

This paper maintains that Reis-Bücklers' corneal dystrophy and granular corneal dystrophy Groenouw type I are one and the same disease. Included are some of the technically best photographs of Reis-Bücklers' dystrophy found in the literature, and these are compared with photographs from patients with granular corneal dystrophy examined by the author. It is argued that most of the histological and ultrastructural findings on Reis Bücklers' dystrophy described in the literature are either congruent with what is found in granular corneal dystrophy or unspecific.

Corneal topographic changes following strabismus surgery in Grave's disease.

PubMed

Kwitko, S; Feldon, S; McDonnell, P J

1992-01-01

A computerized topographic analysis system was used to evaluate corneal changes after strabismus surgery in eight eyes of five patients with Graves' disease. All patients underwent inferior rectus muscle recession; three eyes also had medial rectus recession. Corneal topographic analysis revealed that, postoperatively, corneas steepened inferiorly and inferotemporally at 1.5 mm from corneal apex (p less than 0.05). The opposite effect was observed in the superior quadrant (average flattening of 1.20 +/- 0.32 D at 1.5 mm from corneal apex, and 1.08 +/- 0.39 D at 3.0 mm from corneal apex; p less than 0.05). Superotemporally, the cornea flattened by an average of 0.65 +/- 0.26 D at 3.0 mm from corneal apex, and superonasally 0.72 +/- 0.19 D at 3.0 mm from corneal apex (p less than 0.05). Central, nasal, and temporal cornea did not show statistically significant changes. Spherical equivalent did not change significantly after surgery. The amount of restriction and upgaze measured preoperatively was correlated weakly with inferior corneal steepening (r2 = 0.44; p = 0.046). These results are indicative that corneal topography may be influenced by strabismus surgery for Graves' disease through alteration of extraocular muscle tension or intraocular pressure.

Does corneal hysteresis correlate with endothelial cell density?

PubMed

Akova-Budak, Berna; Kıvanç, Sertaç Argun

2015-05-21

Our aim was to determine if there is a correlation between corneal biomechanical properties, endothelial cell count, and corneal pachymetry in healthy corneas. Ninety-two eyes of all subjects underwent complete ocular examination, including intraocular pressure measurement by Goldmann applanation tonometer, objective refraction, and slit-lamp biomicroscopy. Topographic measurements and corneal pachymetry were performed using a Scheimpflug-based (Pentacam, Oculus, Germany) corneal topographer. Corneal hysteresis (CH) and corneal resistance factor (CRF) were measured with an Ocular Response Analyzer (ORA, Reichert Ophthalmic Instruments, Buffalo, NY). Endothelial cell count measurement was done using a specular microscope (CellChek, Konan, USA). Right eye values of the subjects were taken for the study. The mean CH was 11.5±1.7 mmHg and the mean CRF was 11.2±1.4 mmHg. Mean intraocular pressure was 15.3±2.3 mmHg. The mean endothelial cell count was 2754±205 cells/mm2. No correlation was found between biomechanical properties of cornea and endothelial cell count. There was a significant positive correlation between CH, CRF, and corneal thickness (p<0.001; r=0.79). The corneal biomechanical properties significantly correlated with corneal thickness. We found no correlation between CH and CRF with the endothelial cell density in normal subjects.

Corneal thickness values before and after oxybuprocaine 0.4% eye drops.

PubMed

Asensio, Isabel; Rahhal, Saleh M; Alonso, Luis; Palanca-Sanfrancisco, José M; Sanchis-Gimeno, Juan A

2003-08-01

To determine changes in corneal thickness after topical anesthesia. Corneal thickness was measured before and 3 minutes after administration of two drops of oxybuprocaine 0.4% to 26 patients (26 eyes). We analyzed the corneal thickness of a control group, which was made up of 26 patients (26 eyes) before and 3 minutes after administration of two drops of saline solution. Corneal thickness was measured with the Orbscan Topography System II (Bausch Lomb Surg., Barcelona). Variations higher than +/- 10 microm were found following the instillation of 2 oxybuprocaine eye drops in eight eyes (30.76%) at the inferonasal cornea, in six eyes (23.08%) at the superotemporal, temporal and inferotemporal cornea, in five eyes (19.23%) at the nasal cornea, in three eyes (11.53%) at the central cornea, and in two eyes (7.69%) at the superonasal cornea. Nevertheless, no significant differences in the mean corneal thickness at each corneal location between the first and the second corneal thickness measurements were found in anesthetized eyes. Some individuals can present important increases and decreases in corneal thickness values after anesthetic eye drops. This effect of anesthetic eye drops must be considered by refractive surgeons when carrying out preoperative laser in situ keratomileusis corneal thickness measurements.

Corneal biomechanical data and biometric parameters measured with Scheimpflug-based devices on normal corneas

PubMed Central

Nemeth, Gabor; Szalai, Eszter; Hassan, Ziad; Lipecz, Agnes; Flasko, Zsuzsa; Modis, Laszlo

2017-01-01

AIM To analyze the correlations between ocular biomechanical and biometric data of the eye, measured by Scheimpflug-based devices on healthy subjects. METHODS Three consecutive measurements were carried out using the corneal visualization Scheimpflug technology (CorVis ST) device on healthy eyes and the 10 device-specific parameters were recorded. Pentacam HR-derived parameters (corneal curvature radii on the anterior and posterior surfaces; apical pachymetry; corneal volume; corneal aberration data; depth, volume and angle of the anterior chamber) and axial length (AL) from IOLMaster were correlated with the 10 specific CorVis ST parameters. RESULTS Measurements were conducted in 43 eyes of 43 volunteers (age 61.24±15.72y). The 10 specific CorVis ST data showed significant relationships with corneal curvature radii both on the anterior and posterior surface, pachymetric data, root mean square (RMS) data of lower-order aberrations, and posterior RMS of higher-order aberrations and spherical aberration of the posterior cornea. Anterior chamber depth showed a significant relationship, but there were no significant correlations between corneal volume, anterior chamber volume, mean chamber angle or AL and the 10 specific CorVis ST parameters. CONCLUSIONS CorVis ST-generated parameters are influenced by corneal curvature radii, some corneal RMS data, but corneal volume, anterior chamber volume, chamber angle and AL have no correlation with the biomechanical parameters. The parameters measured by CorVis ST seem to refer mostly to corneal properties of the eye. PMID:28251079

Corneal biomechanical data and biometric parameters measured with Scheimpflug-based devices on normal corneas.

PubMed

Nemeth, Gabor; Szalai, Eszter; Hassan, Ziad; Lipecz, Agnes; Flasko, Zsuzsa; Modis, Laszlo

2017-01-01

To analyze the correlations between ocular biomechanical and biometric data of the eye, measured by Scheimpflug-based devices on healthy subjects. Three consecutive measurements were carried out using the corneal visualization Scheimpflug technology (CorVis ST) device on healthy eyes and the 10 device-specific parameters were recorded. Pentacam HR-derived parameters (corneal curvature radii on the anterior and posterior surfaces; apical pachymetry; corneal volume; corneal aberration data; depth, volume and angle of the anterior chamber) and axial length (AL) from IOLMaster were correlated with the 10 specific CorVis ST parameters. Measurements were conducted in 43 eyes of 43 volunteers (age 61.24±15.72y). The 10 specific CorVis ST data showed significant relationships with corneal curvature radii both on the anterior and posterior surface, pachymetric data, root mean square (RMS) data of lower-order aberrations, and posterior RMS of higher-order aberrations and spherical aberration of the posterior cornea. Anterior chamber depth showed a significant relationship, but there were no significant correlations between corneal volume, anterior chamber volume, mean chamber angle or AL and the 10 specific CorVis ST parameters. CorVis ST-generated parameters are influenced by corneal curvature radii, some corneal RMS data, but corneal volume, anterior chamber volume, chamber angle and AL have no correlation with the biomechanical parameters. The parameters measured by CorVis ST seem to refer mostly to corneal properties of the eye.

Corneal haze following PRK with mitomycin C as a retreatment versus prophylactic use in the contralateral eye.

PubMed

Netto, Marcelo V; Chalita, Maria Regina; Krueger, Ronald R

2007-01-01

To report photorefractive keratectomy (PRK) treated with mitomycin C (MMC) for previous corneal haze in one eye and PRK with MMC to prevent corneal haze formation in the fellow eye. A 40-year-old woman underwent PRK with MMC to treat previous corneal haze (secondary to previous PRK without MMC) for residual refractive error of +0.50 +0.25 x 165 in the left eye and PRK with MMC to prevent corneal haze in the right eye. Postoperative slit-lamp examination revealed no haze in the right eye, but continued mild haze in the left eye. Treatment with PRK and MMC for previous corneal haze is not as effective as primary PRK with MMC in preventing postoperative corneal haze formation.

Short-term effects of overnight orthokeratology on corneal cell morphology and corneal thickness.

PubMed

Nieto-Bona, Amelia; González-Mesa, Ana; Nieto-Bona, Ma Paz; Villa-Collar, César; Lorente-Velázquez, Amalia

2011-06-01

To examine the morphological and biometric corneal changes produced over periods of 15 days and 1 month after overnight orthokeratology (OK). Prospective, single-center, longitudinal trial. Twenty-seven right eyes of 27 subjects (group 1) with low to moderate myopia wore OK lenses for 1 month. Ten right eyes of 10 subjects (group 2) with emmetropia to low myopia who did not wear any type of contact lens served as controls. Corneal morphometric measurements were obtained in vivo using a confocal microscope to examine the central and midperipheral cornea. Thickness measurements in the peripheral cornea were obtained by optical coherence tomography. Changes in visual acuity, refractive error, and corneal topography were also analyzed. No significant changes in either endothelial cell or stromal cell density were observed after 1 month of OK. Basal epithelial cells were, however, significantly reduced (P < 0.01), and epithelial wing and superficial cells showed enhanced visibility (P < 0.05). Superficial cells increased in height and width, the width increase after 1 month being significant (P < 0.01). Epithelial thickness was significantly reduced in the central cornea and 2 mm around the center. Corneal pachymetry increased significantly in the band from 5 to 10 mm from the corneal apex (P < 0.01). OK lenses for myopia induce significant structural and optical changes particularly in the central epithelium after 15 days or 1 month of wear. The central corneal epithelium responds to OK wear by undergoing significant epithelial cell shape and size alterations with no effects, however, on the cells of the corneal endothelium or the corneal stroma. Peripheral corneal thickness increased with respect to baseline values. These findings suggest that the corneal epithelium is the principal structure affected by the mechanical forces exerted by the OK lenses.

Comparison of Anterior, Posterior, and Total Corneal Astigmatism Measured Using a Single Scheimpflug Camera in Healthy and Keratoconus Eyes.

PubMed

Choi, Young; Eom, Youngsub; Song, Jong Suk; Kim, Hyo Myung

2018-05-15

To compare the effect of posterior corneal astigmatism on the estimation of total corneal astigmatism using anterior corneal measurements (simulated keratometry [K]) between eyes with keratoconus and healthy eyes. Thirty-three eyes of 33 patients with keratoconus of grade I or II and 33 eyes of 33 age- and sex-matched healthy control subjects were enrolled. Anterior, posterior, and total corneal cylinder powers and flat meridians measured by a single Scheimpflug camera were analyzed. The difference in corneal astigmatism between the simulated K and total cornea was evaluated. The mean anterior, posterior, and total corneal cylinder powers of the keratoconus group (4.37 ± 1.73, 0.95 ± 0.39, and 4.36 ± 1.74 CD, respectively) were significantly greater than those of the control group (1.10 ± 0.68, 0.39 ± 0.18, and 0.97 ± 0.63 CD, respectively). The cylinder power difference between the simulated K and total cornea was positively correlated with the posterior corneal cylinder power and negatively correlated with the absolute flat meridian difference between the simulated K and total cornea in both groups. The mean magnitude of the vector difference between the astigmatism of the simulated K and total cornea of the keratoconus group (0.67 ± 0.67 CD) was significantly larger than that of the control group (0.28 ± 0.12 CD). Eyes with keratoconus had greater estimation errors of total corneal astigmatism based on anterior corneal measurement than did healthy eyes. Posterior corneal surface measurement should be more emphasized to determine the total corneal astigmatism in eyes with keratoconus. © 2018 The Korean Ophthalmological Society.

Comparison of Anterior, Posterior, and Total Corneal Astigmatism Measured Using a Single Scheimpflug Camera in Healthy and Keratoconus Eyes

PubMed Central

Choi, Young; Song, Jong Suk; Kim, Hyo Myung

2018-01-01

Purpose To compare the effect of posterior corneal astigmatism on the estimation of total corneal astigmatism using anterior corneal measurements (simulated keratometry [K]) between eyes with keratoconus and healthy eyes. Methods Thirty-three eyes of 33 patients with keratoconus of grade I or II and 33 eyes of 33 age- and sex-matched healthy control subjects were enrolled. Anterior, posterior, and total corneal cylinder powers and flat meridians measured by a single Scheimpflug camera were analyzed. The difference in corneal astigmatism between the simulated K and total cornea was evaluated. Results The mean anterior, posterior, and total corneal cylinder powers of the keratoconus group (4.37 ± 1.73, 0.95 ± 0.39, and 4.36 ± 1.74 cylinder diopters [CD], respectively) were significantly greater than those of the control group (1.10 ± 0.68, 0.39 ± 0.18, and 0.97 ± 0.63 CD, respectively). The cylinder power difference between the simulated K and total cornea was positively correlated with the posterior corneal cylinder power and negatively correlated with the absolute flat meridian difference between the simulated K and total cornea in both groups. The mean magnitude of the vector difference between the astigmatism of the simulated K and total cornea of the keratoconus group (0.67 ± 0.67 CD) was significantly larger than that of the control group (0.28 ± 0.12 CD). Conclusions Eyes with keratoconus had greater estimation errors of total corneal astigmatism based on anterior corneal measurement than did healthy eyes. Posterior corneal surface measurement should be more emphasized to determine the total corneal astigmatism in eyes with keratoconus. PMID:29770640

Corneal densitometry and its correlation with age, pachymetry, corneal curvature, and refraction.

PubMed

Garzón, Nuria; Poyales, Francisco; Illarramendi, Igor; Mendicute, Javier; Jáñez, Óscar; Caro, Pedro; López, Alfredo; Argüeso, Francisco

2017-12-01

To determine normative corneal densitometry values in relation to age, sex, refractive error, corneal thickness, and keratometry, measured using the Oculus Pentacam system. Three hundred and thirty-eight healthy subjects (185 men; 153 women) with no corneal disease underwent an exhaustive ocular examination. Corneal densitometry was expressed in standardized grayscale units (GSU). The mean corneal densitometry over the total area was 16.46 ± 1.85 GSU. The Pearson correlation coefficient for total densitometry was r = 0.542 (p < 0.001). Statistically significant differences were found between men and women for the total area (p = 0.006), with readings of 16.22 ± 1.54 GSU and 16.60 ± 1.83 GSU, respectively. When the cornea was divided into layers of different depths, a significant correlation was found for all layers and age: r = 0.447 (p < 0.001), r = 0.563 (p < 0.001), and r = 0.520 (p < 0.001) for the anterior, central, and posterior layers, respectively. However, when the cornea was divided into concentric annuli starting from the center of the cornea, densitometry was strongly correlated only with age in the 6-10-mm annulus (p < 0.001). Neither mean keratometry nor spherical equivalent was correlated with corneal densitometry in any zone of the cornea (p > 0.05). This is the first report of normative corneal densitometry values in relation to keratometry, corneal thickness, and spherical equivalent measured with the latest Oculus Pentacam software. Corneal densitometry increases with age, but corneal keratometry and refractive parameters do not affect light scattering in the human cornea.

Using corneal confocal microscopy to track changes in the corneal layers of dry eye patients after autologous serum treatment.

PubMed

Mahelkova, Gabriela; Jirsova, Katerina; Seidler Stangova, Petra; Palos, Michalis; Vesela, Viera; Fales, Ivan; Jiraskova, Nada; Dotrelova, Dagmar

2017-05-01

In vivo corneal confocal microscopy allows the examination of each layer of the cornea in detail and the identification of pathological changes at the cellular level. The purpose of this study was to identify the possible effects of a three-month treatment with autologous serum eye-drops in different corneal layers of patients with severe dry eye disease using corneal confocal microscopy. Twenty-six patients with dry eye disease were included in the study. Corneal fluorescein staining was performed. The corneas of the right eyes were examined using in vivo corneal confocal microscopy before and after a three-month treatment with autologous serum drops. The densities of superficial and basal epithelial cells, Langerhans cells, the keratocytes and activated keratocytes, the density of endothelial cells and the status of the sub-basal nerve plexus fibres were evaluated. A significant decrease in corneal fluorescein staining was found after the three-month autologous serum treatment (p = 0.0006). The basal epithelial cell density decreased significantly (p = 0.001), while the density of superficial epithelial cells did not change significantly (p = 0.473) nor did the number of Langerhans cells or activated keratocytes (p = 0.223; p = 0.307, respectively). There were no differences in the other corneal cell layers or in the status of the nerve fibres. The results demonstrate the ability of corneal confocal microscopy to evaluate an improvement in the basal epithelial cell layer of the cornea after autologous serum treatment in patients with dry eye disease. More studies with longer follow-up periods are needed to elucidate the suitability of corneal confocal microscopy to follow the effect of autologous serum treatment on nerve fibres or other corneal layers in dry eye disease patients. © 2016 Optometry Australia.

Structure-function relationship between the octopus perimeter cluster mean sensitivity and sector retinal nerve fiber layer thickness measured with the RTVue optical coherence tomography and scanning laser polarimetry.

PubMed

Naghizadeh, Farzaneh; Garas, Anita; Vargha, Péter; Holló, Gábor

2014-01-01

To determine structure-function relationship between each of 16 Octopus perimeter G2 program clusters and the corresponding 16 peripapillary sector retinal nerve fiber layer thickness (RNFLT) values measured with the RTVue-100 Fourier-domain optical coherence tomography (RTVue OCT) and scanning laser polarimetry with variable corneal compensation (GDx-VCC) and enhanced corneal compensation (GDx-ECC) corneal compensation. One eye of 110 white patients (15 healthy, 20 ocular hypertensive, and 75 glaucoma eyes) were investigated. The Akaike information criterion and the F test were used to identify the best fitting model. Parabolic relationship with logarithmic cluster mean sensitivity and linear sector RNFLT values provided the best fit. For RTVue OCT, significant (P<0.0001) coefficients of determination (R) were found for all 16 RNFLT sectors. The R values were highest for the temporal, superotemporal, and inferotemporal RNFLT sectors (0.4483 to 0.5186). For GDx-VCC/ECC, significant (P<0.01) parabolic relationship was seen for all but the temporal and nasal RNFLT sectors. The overall highest R value (0.6943) was found for a superotemporal RNFLT sector with GDx-ECC. For some RNFLT sectors, the goodness of fit differed significantly between the imaging methods. Structure-function relationship was similar for the total population and the glaucoma subgroup, whereas no relationship (P>0.05) was found for the control eyes. Mean sensitivity of the Octopus visual field clusters showed significant parabolic relationship with the corresponding peripapillary RNFLT sectors. The relationship was more general with the RTVue OCT than GDx-VCC or GDx-ECC. The results show that visual field clusters of the Octopus G program can be applied for detailed structure-function research.

In situ ultrahigh-resolution optical coherence tomography characterization of eye bank corneal tissue processed for lamellar keratoplasty.

PubMed

Brown, Jamin S; Wang, Danling; Li, Xiaoli; Baluyot, Florence; Iliakis, Bernie; Lindquist, Thomas D; Shirakawa, Rika; Shen, Tueng T; Li, Xingde

2008-08-01

To use optical coherence tomography (OCT) as a noninvasive tool to perform in situ characterization of eye bank corneal tissue processed for lamellar keratoplasty. A custom-built ultrahigh-resolution OCT (UHR-OCT) was used to characterize donor corneal tissue that had been processed for lamellar keratoplasty. Twenty-seven donor corneas were analyzed. Four donor corneas were used as controls, whereas the rest were processed into donor corneal buttons for lamellar transplantation by using hand dissection, a microkeratome, or a femtosecond laser. UHR-OCT was also used to noninvasively characterize and monitor the viable corneal tissue immersed in storage medium over 3 weeks. The UHR-OCT captured high-resolution images of the donor corneal tissue in situ. This noninvasive technique showed the changes in donor corneal tissue morphology with time while in storage medium. The characteristics of the lamellar corneal tissue with each processing modality were clearly visible by UHR-OCT. The in situ characterization of the femtosecond laser-cut corneal tissue was noted to have more interface debris than shown by routine histology. The effects of the femtosecond laser microcavitation bubbles on the corneal tissue were well visualized at the edges of the lamellar flap while in storage medium. The results of our feasibility study show that UHR-OCT can provide superb, in situ microstructural characterization of eye bank corneal tissue noninvasively. The UHR-OCT interface findings and corneal endothelial disc thickness uniformity analysis are valuable information that may be used to optimize the modalities and parameters for lamellar tissue processing. The UHR-OCT is a powerful approach that will allow us to further evaluate the tissue response to different processing techniques for posterior lamellar keratoplasty. It may also provide information that can be used to correlate with postoperative clinical outcomes. UHR-OCT has the potential to become a routine part of tissue analysis for any eye bank or centers creating customized lamellar corneal tissue for transplantation.

A brief review of Boston type-1 and osteo-odonto keratoprostheses.

PubMed

Avadhanam, Venkata S; Liu, Christopher S C

2015-07-01

Globally there are ≈4.9 million bilaterally corneal blind and 23 million unilaterally corneal blind. Majority of this blindness exists in the developing countries, where resources for corneal banking and transplant surgery are less than adequate. Survival of corneal grafts gradually declines over the long term. Corneal transplantation has poor prognosis in vascularised corneal beds, ocular surface disease and viral keratitis. Keratoprosthesis (KPro) remains as a final option for end-stage ocular surface disease, multiple corneal transplant failures and high-risk corneal grafts. Boston type-1 KPro and osteo-odonto-keratoprosthesis are the two devices proven useful in recent years. Choice of a keratoprosthetic device is patient specific based on the underlying diagnosis, ocular morbidity and patient suitability. KPro surgery demands a high level of clinical and surgical expertise, lifelong commitment and extensive resources. Improvements in techniques and biomaterials may in the future provide retainable KPros that do not need regular follow-up of patients, have low complications but high retention rates and may be produced at a low cost on a mass scale to be available as 'off the shelf' devices. Because KPros have the potential to effectively address the burden of surgically treatable corneal blindness and may also eliminate the problems of corneal transplantation, more research is required to develop KPros as substitutes for corneal transplantation even in low-risk cases. In those countries where corneal blindness is a major liability, we need a two pronged approach: one to develop eye donation, eye banking and corneal transplantation and the second to establish centres for keratoprostheses, which are affordable and technically not challenging, in a population where default on follow-up visits are high. Until the latter is achieved, KPros should be viewed as a temporary means for visual restoration and be offered in national and supraregional specialised centres only. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Laser-assisted cataract surgery: benefits and barriers.

PubMed

Hatch, Kathryn M; Talamo, Jonathan H

2014-01-01

The use of the femtosecond laser (FSL) in cataract surgery may represent the largest advancement in the field since the inception of phacoemulsification. The goal of this review is to outline the benefits of and barriers to this technology. There are several significant potential benefits of the FSL in cataract surgery over conventional manual cataract surgery: precise capsulotomy formation, clear corneal and limbal relaxing incision construction, lens fragmentation, and lens softening. Evidence suggests that refractive benefits include more precise effective lens position as well as reduced effective phacoemulsification time with the use of FSL compared with manual surgery. Patients with conditions such as Fuchs' endothelial dystrophy, pseudoexfoliation, history of trauma, or brunescent cataracts may particularly benefit from this technology. There are significant financial and logistical issues to consider prior to the purchase of a FSL, including the cost of the laser, and charges to patients, and how the laser affects the patient flow in the operating room. The FSL may significantly change the current approach to cataract surgery.

Punctiform and Polychromatophilic Dominant Pre-Descemet Corneal Dystrophy.

PubMed

Lagrou, Lisa; Midgley, Julian; Romanchuk, Kenneth Gerald

2016-04-01

To describe the slit-lamp appearance and corneal confocal microscopy of autosomal dominant punctiform and polychromatophilic pre-Descemet corneal dystrophy in 3 members of the same family. Slit-lamp examination of a 9-year-old boy showed bilateral polychromatophilic corneal opacities in a pre-Descemet membrane location evenly deposited limbus to limbus, both horizontally and vertically, with an intervening clear cornea. The corneal endothelium was normal on corneal confocal microscopy, with hyperreflective opacities of various sizes located pre-Descemet membrane. Slit-lamp examination of the patient's father and brother revealed identical crystalline deposition in the pre-Descemet corneal stroma. The remainders of the eye examinations were otherwise normal in all 3 individuals, and all were asymptomatic. The general physical examination and laboratory investigations of the patient were all normal, as were the laboratory investigations of the other 2 family members. There was no progression in the corneal findings over 6 months of follow-up. These patients likely illustrate a rare autosomal dominant pre-Descemet crystalline keratopathy that has been reported only once previously.

Osteo-odonto keratoprosthesis in Stevens-Johnson syndrome: a case report

PubMed Central

SC, Reddy; I, Tajunisah; T, Tan D

2011-01-01

AIM To report a successful osteo-odonto keratoprosthesis (OOKP) procedure in a case of end stage of corneal blindness due to Stevens-Johnson syndrome (SJS). METHODS An interventional case report. RESULTS We describe a 35-year-old Indian woman, a known case of SJS with bilateral dry eyes and corneal blindness (failed corneal graft with vascularised total corneal opacity in the right eye and non-healing corneal ulcer in the left eye). Vision was hand movement only in both eyes. The corneal ulcer healed with medical treatment resulting in vascularised total corneal opacity with no improvement in vision. OOKP was performed in the right eye and the vision was improved from hand movement to 6/6. The same vision was maintained in the right eye at the last follow-up 5 years after surgery. CONCLUSION OOKP provides good visual rehabilitation with long-term anatomically stable prosthesis in patients with end-stage of ocular surface disorders and corneal blindness secondary to SJS. PMID:22553646

Corneal cell culture models: a tool to study corneal drug absorption.

PubMed

Dey, Surajit

2011-05-01

In recent times, there has been an ever increasing demand for ocular drugs to treat sight threatening diseases such as glaucoma, age-related macular degeneration and diabetic retinopathy. As more drugs are developed, there is a great need to test in vitro permeability of these drugs to predict their efficacy and bioavailability in vivo. Corneal cell culture models are the only tool that can predict drug absorption across ocular layers accurately and rapidly. Cell culture studies are also valuable in reducing the number of animals needed for in vivo studies which can increase the cost of the drug developmental process. Currently, rabbit corneal cell culture models are used to predict human corneal absorption due to the difficulty in human corneal studies. More recently, a three dimensional human corneal equivalent has been developed using three different cell types to mimic the human cornea. In the future, human corneal cell culture systems need to be developed to be used as a standardized model for drug permeation.

Evaluation of Corneal Neovascularization Using Optical Coherence Tomography Angiography in Patients With Limbal Stem Cell Deficiency.

PubMed

Oie, Yoshinori; Nishida, Kohji

2017-11-01

Detection of the exact area of corneal neovascularization using slit-lamp photography is often difficult. Thus, we evaluated corneal neovascularization in patients with limbal stem cell deficiency using optical coherence tomography angiography (OCTA). Five patients with 5 eyes showing partial or total limbal stem cell deficiency were enrolled. Three eyes had severe corneal scarring. Five 6- × 6-mm images (frontal, upper, lower, nasal, and temporal) were obtained by OCTA. Slit-lamp photography was performed for all patients on the same day. OCTA has 2 advantages over slit-lamp photography for clear demonstration of corneal neovascularization. First, OCTA can show neovascularization in cases with severe corneal opacification. Second, OCTA can detect not only large vessels but also small vessels that cannot be seen by slit-lamp photography. OCTA is a powerful tool for objective evaluation of vascularization in the anterior and posterior segments of the eye. We have demonstrated that OCTA can visualize corneal neovascularization in patients with corneal diseases more clearly than slit-lamp photography.

Corneal Nerves in Health and Disease

PubMed Central

Shaheen, Brittany; Bakir, May; Jain, Sandeep

2013-01-01

Corneal nerves are responsible for the sensations of touch, pain, and temperature and play an important role in the blink reflex, wound healing, and tear production and secretion. Corneal nerve dysfunction is a frequent feature of diseases that cause opacities and result in corneal blindness. Corneal opacities rank as the second most frequent cause of blindness. Technological advances in in vivo corneal nerve imaging, such as optical coherence tomography and confocal scanning, have generated new knowledge regarding the phenomenological events that occur during reinnervation of the cornea following disease, injury, or surgery. The recent availability of transgenic neurofluorescent murine models has stimulated the search for molecular modulators of corneal nerve regeneration. New evidence suggests that neuro-regenerative and inflammatory pathways in the cornea are intertwined. Evidence-based treatment of neurotrophic corneal diseases includes using neuro-regenerative (blood component-based and neurotrophic factors), neuroprotective, and ensconcing (bandage contact lens and amniotic membrane) strategies and avoiding anti-inflammatory therapies, such as cyclosporine and corticosteroids. PMID:24461367

Fungal corneal ulcer and bacterial orbital cellulitis occur as complications of bacterial endophthalmitis after cataract surgery in an immunocompetent patient.

PubMed

Kim, Eun Chul; Kim, Man Soo; Kang, Nam Yeo

2013-03-01

To report a case of fungal corneal ulcer and bacterial orbital cellulitis as complications of bacterial endophthalmitis following cataract surgery. A 51-year-old man underwent anterior chamber irrigation and aspiration in the left eye one day after cataract surgery because of bacterial endophthalmitis. Marked lid swelling with purulent discharge was developed after 5 days. Slit lamp examination showed generalized corneal ulcer and pus in the total anterior chamber. A computerized tomography scan showed left retrobulbar fat stranding with thickened optic disc. Streptococcus pneumonia was cultured from corneal scraping, vireous, and subconjunctival pus. The patient improved gradually with antibiotics treatments, but the corneal ulcer did not fully recover 2 months after cataract surgery. Candida albicans was detected in repetitive corneal culture. After antifungal and antibacterial therapy, the corneal epithelium had healed, but phthisis bulbi had developed. Fungal corneal ulcer and bacterial orbital cellulitis can occur as complications of endophthalmitis in an immunocompetent patient.

Femtosecond laser correction of presbyopia (INTRACOR) in emmetropes using a modified pattern.

PubMed

Thomas, Bettina C; Fitting, Anna; Auffarth, Gerd U; Holzer, Mike P

2012-12-01

To evaluate functional results and corneal changes after femtosecond laser correction of presbyopia (INTRACOR, Technolas Perfect Vision GmbH) in emmetropes using a modified treatment pattern over a 12-month period. Twenty eyes from 20 emmetropic patients were treated with a modified intrastromal INTRACOR pattern consisting of 5 central rings and 8 radial cuts in a prospective, nonrandomized, uncontrolled, open, single-center, clinical study. Refraction, visual acuity, endothelial cell density, corneal pachymetry, total corneal power, and stray light were evaluated preoperatively and 1 (except endothelial cell density and stray light), 3, 6, and 12 months postoperatively. Patients filled out a subjective questionnaire at 12 months postoperatively. Comparison of preoperative versus 12-month postoperative median values revealed a significant improvement in uncorrected near visual acuity (UNVA) from 0.60 (20/80) to 0.10 logMAR (20/25) (P<.0001) and a significant decrease in corrected distance visual acuity (CDVA) from -0.10 (20/16) to 0.00 logMAR (20/20), which equals a median loss of one line (P=.0005). Fifteen percent of patients lost two lines of CDVA in the treated eye. Subjective spherical equivalent refraction remained unchanged at 0.00 diopters (D) (P=.194). After INTRACOR treatment, significant corneal steepening of 1.40 D and midperipheral flattening of 0.50 D occurred (both P<.0001). Corneal pachymetry at the thinnest point and endothelial cell density did not change significantly (P=.829 and P=.058, respectively). After 12 months, the modified INTRACOR pattern improved UNVA in emmetropic patients without inducing a myopic shift or significant changes in endothelial cell density or pachymetry. Copyright 2012, SLACK Incorporated.

Menadione-Induced DNA Damage Leads to Mitochondrial Dysfunction and Fragmentation During Rosette Formation in Fuchs Endothelial Corneal Dystrophy

PubMed Central

Halilovic, Adna; Schmedt, Thore; Benischke, Anne-Sophie; Hamill, Cecily; Chen, Yuming; Santos, Janine Hertzog

2016-01-01

Abstract Aims: Fuchs endothelial corneal dystrophy (FECD), a leading cause of age-related corneal edema requiring transplantation, is characterized by rosette formation of corneal endothelium with ensuing apoptosis. We sought to determine whether excess of mitochondrial reactive oxygen species leads to chronic accumulation of oxidative DNA damage and mitochondrial dysfunction, instigating cell death. Results: We modeled the pathognomonic rosette formation of postmitotic corneal cells by increasing endogenous cellular oxidative stress with menadione (MN) and performed a temporal analysis of its effect in normal (HCEnC, HCECi) and FECD (FECDi) cells and ex vivo specimens. FECDi and FECD ex vivo specimens exhibited extensive mtDNA and nDNA damage as detected by quantitative PCR. Exposure to MN triggered an increase in mitochondrial superoxide levels and led to mtDNA and nDNA damage, while DNA amplification was restored with NAC pretreatment. Furthermore, MN exposure led to a decrease in ΔΨm and adenosine triphosphate levels in normal cells, while FECDi exhibited mitochondrial dysfunction at baseline. Mitochondrial fragmentation and cytochrome c release were detected in FECD tissue and after MN treatment of HCEnCs. Furthermore, cleavage of caspase-9 and caspase-3 followed MN-induced cytochrome c release in HCEnCs. Innovation: This study provides the first line of evidence that accumulation of oxidative DNA damage leads to rosette formation, loss of functionally intact mitochondria via fragmentation, and subsequent cell death during postmitotic cell degeneration of ocular tissue. Conclusion: MN induced rosette formation, along with mtDNA and nDNA damage, mitochondrial dysfunction, and fragmentation, leading to activation of the intrinsic apoptosis via caspase cleavage and cytochrome c release. Antioxid. Redox Signal. 24, 1072–1083. PMID:26935406

Menadione-Induced DNA Damage Leads to Mitochondrial Dysfunction and Fragmentation During Rosette Formation in Fuchs Endothelial Corneal Dystrophy.

PubMed

Halilovic, Adna; Schmedt, Thore; Benischke, Anne-Sophie; Hamill, Cecily; Chen, Yuming; Santos, Janine Hertzog; Jurkunas, Ula V

2016-06-20

Fuchs endothelial corneal dystrophy (FECD), a leading cause of age-related corneal edema requiring transplantation, is characterized by rosette formation of corneal endothelium with ensuing apoptosis. We sought to determine whether excess of mitochondrial reactive oxygen species leads to chronic accumulation of oxidative DNA damage and mitochondrial dysfunction, instigating cell death. We modeled the pathognomonic rosette formation of postmitotic corneal cells by increasing endogenous cellular oxidative stress with menadione (MN) and performed a temporal analysis of its effect in normal (HCEnC, HCECi) and FECD (FECDi) cells and ex vivo specimens. FECDi and FECD ex vivo specimens exhibited extensive mtDNA and nDNA damage as detected by quantitative PCR. Exposure to MN triggered an increase in mitochondrial superoxide levels and led to mtDNA and nDNA damage, while DNA amplification was restored with NAC pretreatment. Furthermore, MN exposure led to a decrease in ΔΨm and adenosine triphosphate levels in normal cells, while FECDi exhibited mitochondrial dysfunction at baseline. Mitochondrial fragmentation and cytochrome c release were detected in FECD tissue and after MN treatment of HCEnCs. Furthermore, cleavage of caspase-9 and caspase-3 followed MN-induced cytochrome c release in HCEnCs. This study provides the first line of evidence that accumulation of oxidative DNA damage leads to rosette formation, loss of functionally intact mitochondria via fragmentation, and subsequent cell death during postmitotic cell degeneration of ocular tissue. MN induced rosette formation, along with mtDNA and nDNA damage, mitochondrial dysfunction, and fragmentation, leading to activation of the intrinsic apoptosis via caspase cleavage and cytochrome c release. Antioxid. Redox Signal. 24, 1072-1083.

Involvement of Sp1 elements in the promoter activity of genes affected in keratoconus.

PubMed

Maruyama, Y; Wang, X; Li, Y; Sugar, J; Yue, B Y

2001-08-01

Keratoconus is a progressive disease that thins and scars the corneal stroma. In keratoconus corneas, levels of degradative enzymes, including lysosomal acid phosphatase (LAP) and cathepsin B, are elevated, and those of the inhibitors alpha1-proteinase inhibitor (alpha 1-PI) and alpha 2-macroglobulin (alpha 2-M) are reduced, especially in the epithelial layer. An increased expression of the transcription factor Sp1 was also demonstrated. The role of Sp1 in regulation of the genes affected in keratoconus was examined in this study. DNA segments, containing 5'-flanking promoter sequences of the alpha 1-PI, LAP, cathepsin B, and alpha 2-M genes were ligated into the secreted alkaline phosphatase (SEAP) reporter gene vector. These constructs, along with the pSV beta-galactosidase control vector, were transfected into cultured human corneal epithelial and stromal cells and skin fibroblasts. Cotransfection with the Sp1 expression vector was performed in parallel. SEAP and beta-galactosidase enzyme activities were assayed. In corneal epithelial cells, as in stromal cells, alpha 1-PI promoter activity was suppressed by cotransfection of pPacSp1. The LAP, cathepsin B, and alpha 2-M promoters were functional in corneal cells, whereas activities of these promoters were much lower in skin fibroblasts. Cotransfection experiments indicated that the up- or downregulation of LAP, cathepsin B, and alpha 2-M observed in keratoconus-affected corneas was not mediated by Sp1. These results support the theory that the corneal epithelium, along with the stroma, is involved in keratoconus. An upstream role of Sp1 is indicated and the Sp1-mediated downregulation of the alpha 1-PI gene may be a key event in the disease development.

MRP8/14 Enhances Corneal Susceptibility to Pseudomonas aeruginosa Infection by Amplifying Inflammatory Responses

PubMed Central

Deng, Qiuchan; Sun, Mingxia; Yang, Kun; Zhu, Min; Chen, Kang; Yuan, Jin; Wu, Minhao; Huang, Xi

2013-01-01

Purpose. We explored the role of myeloid-related protein 8 and 14 (MRP8/14) in Pseudomonas aeruginosa (PA) keratitis. Methods. MRP8/14 mRNA levels in human corneal scrapes and mouse corneas infected by PA were tested using real-time PCR. MRP8/14 protein expression in C57BL/6 (B6) corneas was confirmed using Western blot assay and immunohistochemistry. B6 mice were injected subconjunctivally with siRNA for MRP8/14, and then infected with PA. Bacterial plate counts and myeloperoxidase assays were used to determine the bacterial load and polymorphonuclear neutrophil (PMN) infiltration in infected B6 corneas. Pro-inflammatory cytokine levels in vivo and in vitro were examined with PCR and ELISA. In murine macrophage-like RAW264.7 cells, phagocytosis and bacterial killing were assessed using plate count assays, and reactive oxygen species (ROS) and nitric oxide (NO) levels were tested with flow cytometry and Griess assay, respectively. Results. MRP8/14 expression levels were increased significantly in human corneal scrapes and B6 corneas after PA infection. Silencing of MRP8/14 in B6 corneas significantly reduced the severity of corneal disease, bacterial clearance, PMN infiltration, and pro-inflammatory cytokine expression after PA infection. In vitro studies demonstrated further that silencing of MRP8/14 suppressed pro-inflammatory cytokine production, bacterial killing, and ROS production, but not phagocytosis or NO production. Conclusions. Our study demonstrated a dual role for MRP8/14 in bacterial keratitis. Although MRP8/14 promotes bacterial clearance by enhancing ROS production, it functions more importantly as an inflammatory amplifier at the ocular surface by enhancing pro-inflammatory cytokine expression, thus contributing to the corneal susceptibility. PMID:23299480

On-line 3-dimensional confocal imaging in vivo.

PubMed

Li, J; Jester, J V; Cavanagh, H D; Black, T D; Petroll, W M

2000-09-01

In vivo confocal microscopy through focusing (CMTF) can provide a 3-D stack of high-resolution corneal images and allows objective measurements of corneal sublayer thickness and backscattering. However, current systems require time-consuming off-line image processing and analysis on multiple software platforms. Furthermore, there is a trade off between the CMTF speed and measurement precision. The purpose of this study was to develop a novel on-line system for in vivo corneal imaging and analysis that overcomes these limitations. A tandem scanning confocal microscope (TSCM) was used for corneal imaging. The TSCM video camera was interfaced directly to a PC image acquisition board to implement real-time digitization. Software was developed to allow in vivo 2-D imaging, CMTF image acquisition, interactive 3-D reconstruction, and analysis of CMTF data to be performed on line in a single user-friendly environment. A procedure was also incorporated to separate the odd/even video fields, thereby doubling the CMTF sampling rate and theoretically improving the precision of CMTF thickness measurements by a factor of two. In vivo corneal examinations of a normal human and a photorefractive keratectomy patient are presented to demonstrate the capabilities of the new system. Improvements in the convenience, speed, and functionality of in vivo CMTF image acquisition, display, and analysis are demonstrated. This is the first full-featured software package designed for in vivo TSCM imaging of the cornea, which performs both 2-D and 3-D image acquisition, display, and processing as well as CMTF analysis. The use of a PC platform and incorporation of easy to use, on line, and interactive features should help to improve the clinical utility of this technology.

Down-regulation of Pax6 is associated with abnormal differentiation of corneal epithelial cells in severe ocular surface diseases

PubMed Central

Li, W; Chen, Y-T; Hayashida, Y; Blanco, G; Kheirkah, A; He, H; Chen, S-Y; Liu, C-Y; Tseng, SCG

2010-01-01

Pax6 is the universal master control gene for eye morphogenesis. Other than retina and lens, Pax6 also expressed in the ocular surface epithelium from early gestation until the postnatal stage, in which little is known about the function of Pax6. In this study, corneal pannus tissues from patients with ocular surface diseases such as Stevens–Johnson syndrome (SJS), chemical burn, aniridia and recurrent pterygium were investigated. Our results showed that normal ocular surface epithelial cells expressed Pax6. However, corneal pannus epithelial cells from the above patients showed a decline or absence of Pax6 expression, accompanied by a decline or absence of K12 keratin but an increase of K10 keratin and filaggrin expression. Pannus basal epithelial cells maintained nuclear p63 expression and showed activated proliferation, evidenced by positive Ki67 and K16 keratin staining. On 3T3 fibroblast feeder layers, Pax6 immunostaining was negative in clones generated from epithelial cells harvested from corneal pannus from SJS or aniridia, but positive in those from the normal limbal epithelium; whereas western blots showed that some epithelial clones expanded from pannus retained Pax6 expression. Transient transfection of an adenoviral vector carrying EGFP–Pax6 transgenes into these Pax6− clones increased both Pax6 and K12 keratin expression. These results indicate that Pax6 helps to maintain the normal corneal epithelial phenotype postnatally, and that down-regulation of Pax6 is associated with abnormal epidermal differentiation in severe ocular surface diseases. Reintroduction of activation of the Pax6 gene might be useful in treating squamous metaplasia of the ocular surface epithelium. PMID:18027901

Dependence of corneal stem/progenitor cells on ocular surface innervation.

PubMed

Ueno, Hiroki; Ferrari, Giulio; Hattori, Takaaki; Saban, Daniel R; Katikireddy, Kishore R; Chauhan, Sunil K; Dana, Reza

2012-02-21

Neurotrophic keratopathy (NK) is a corneal degeneration associated with corneal nerve dysfunction. It can cause corneal epithelial defects, stromal thinning, and perforation. However, it is not clear if and to which extent epithelial stem cells are affected in NK. The purpose of this study was to identify the relationship between corneolimbal epithelial progenitor/stem cells and sensory nerves using a denervated mouse model of NK. NK was induced in mice by electrocoagulation of the ophthalmic branch of the trigeminal nerve. The absence of corneal nerves was confirmed with β-III tubulin immunostaining and blink reflex test after 7 days. ATP-binding cassette subfamily G member 2 (ABCG2), p63, and hairy enhancer of split 1 (Hes1) were chosen as corneolimbal stem/progenitor cell markers and assessed in denervated mice versus controls by immunofluorescent microscopy and real-time PCR. In addition, corneolimbal stem/progenitor cells were detected as side population cells using flow cytometry, and colony-forming efficiency assay was performed to assess their function. ABCG2, p63, and Hes1 immunostaining were significantly decreased in denervated eyes after 7 days. Similarly, the expression levels of ABCG2, p63, K15, Hes1, and N-cadherin transcripts were also significantly decreased in denervated eyes. Stem/progenitor cells measured as side population from NK mice were decreased by approximately 75% compared with normals. In addition, the authors found a significant (P = 0.038) reduction in colony-forming efficiency of stem/progenitor cells harvested from denervated eyes. Corneolimbal stem/progenitor cells are significantly reduced after depletion of sensory nerves. The data suggest a critical role of innervation in maintaining stem cells and/or the stem cell niche.

Dependence of Corneal Stem/Progenitor Cells on Ocular Surface Innervation

PubMed Central

Ueno, Hiroki; Ferrari, Giulio; Hattori, Takaaki; Saban, Daniel R.; Katikireddy, Kishore R.; Chauhan, Sunil K.

2012-01-01

Purpose. Neurotrophic keratopathy (NK) is a corneal degeneration associated with corneal nerve dysfunction. It can cause corneal epithelial defects, stromal thinning, and perforation. However, it is not clear if and to which extent epithelial stem cells are affected in NK. The purpose of this study was to identify the relationship between corneolimbal epithelial progenitor/stem cells and sensory nerves using a denervated mouse model of NK. Methods. NK was induced in mice by electrocoagulation of the ophthalmic branch of the trigeminal nerve. The absence of corneal nerves was confirmed with β-III tubulin immunostaining and blink reflex test after 7 days. ATP-binding cassette subfamily G member 2 (ABCG2), p63, and hairy enhancer of split 1 (Hes1) were chosen as corneolimbal stem/progenitor cell markers and assessed in denervated mice versus controls by immunofluorescent microscopy and real-time PCR. In addition, corneolimbal stem/progenitor cells were detected as side population cells using flow cytometry, and colony-forming efficiency assay was performed to assess their function. Results. ABCG2, p63, and Hes1 immunostaining were significantly decreased in denervated eyes after 7 days. Similarly, the expression levels of ABCG2, p63, K15, Hes1, and N-cadherin transcripts were also significantly decreased in denervated eyes. Stem/progenitor cells measured as side population from NK mice were decreased by approximately 75% compared with normals. In addition, the authors found a significant (P = 0.038) reduction in colony-forming efficiency of stem/progenitor cells harvested from denervated eyes. Conclusions. Corneolimbal stem/progenitor cells are significantly reduced after depletion of sensory nerves. The data suggest a critical role of innervation in maintaining stem cells and/or the stem cell niche. PMID:22232434

Limited Versus Total Epithelial Debridement Ocular Surface Injury: Live Fluorescence Imaging of Hemangiogenesis and Lymphangiogenesis in Prox1-GFP/Flk1::myr-mCherry Mice

PubMed Central

Chang, Jin-Hong; Putra, Ilham; Huang, Yu-hui; Chang, Michael; Han, Kyuyeon; Zhong, Wei; Gao, Xinbo; Wang, Shuangyong; Dugas-Ford, Jennifer; Nguyen, Tara; Hong, Young-Kwon; Azar, Dimitri T.

2016-01-01

Background Immunohistochemical staining experiments have shown that both hemangiogenesis and lymphangiogenesis occur following severe corneal and conjunctival injury and that the neovascularization of the cornea often has severe visual consequences. To better understand how hemangiogenesis and lymphangiogenesis are induced by different degrees of ocular injury, we investigated patterns of injury-induced corneal neovascularization in live Prox1-GFP/Flk1::myr-mCherry mice, in which blood and lymphatic vessels can be imaged simultaneously in vivo. Methods The eyes of Prox1-GFP/Flk1::myr-mCherry mice were injured according to four models based on epithelial debridement of the: A) central cornea (a 1.5-mm-diameter circle of tissue over the corneal apex), B) total cornea, C) bulbar conjunctiva, and D) cornea+bulbar conjunctiva. Corneal blood and lymphatic vessels were imaged on days 0, 3, 7, and 10 post-injury, and the percentages of the cornea containing blood and lymphatic vessels were calculated. Results Neither central corneal nor bulbar conjunctival debridement resulted in significant vessel growth in the mouse cornea, whereas total corneal and corneal+bulbar conjunctival debridement did. On day 10 in the central cornea, total cornea, bulbar conjunctiva, and corneal+bulbar conjunctival epithelial debridement models, the percentage of the corneal surface that was occupied by blood vessels (hemangiogenesis) was 1.9±0.8%, 7.14±2.4%, 2.29±1%, and 15.05±2.14%, respectively, and the percentage of the corneal surface that was occupied by lymphatic vessels (lymphangiogenesis) was 2.45±1.51%, 4.85±0.95%, 2.95±1.27%, and 4.15±3.85%, respectively. Conclusions Substantial corneal debridement was required to induce corneal neovascularization in the mouse cornea, and the corneal epithelium may therefore be partially responsible for maintaining corneal avascularity. General significance Our study demonstrates that GFP/Flk1::myr-mCherry mice are a useful model for studying coordinated hemangiogenic and lymphangiogenic responses. PMID:27233452

Corneal clouding in Alport syndrome.

PubMed

Herwig, Martina C; Eter, Nicole; Holz, Frank G; Loeffler, Karin U

2011-03-01

Alport syndrome is a hereditary basement membrane disease that typically involves the kidney, the cochlea, and the eyes. Characteristic ocular problems include posterior polymorphous corneal dystrophy, lenticonus, and dot-and-fleck retinopathy. A 48-year-old male patient with Alport syndrome presented with corneal and retinal changes. In 2003, he was diagnosed with posterior polymorphous corneal dystrophy and received a corneal transplant in his left eye in 2007 because of progressive deterioration in visual acuity. At this time, a lamellar macular hole was diagnosed in his right eye. The removed corneal button was examined by light and electron microscopy and by immunohistochemistry. Histology revealed not only endothelial changes but also a marked irregular thickening of the epithelial basement membrane and of Bowman layer. Alcian blue staining demonstrated an accumulation of mucopolysaccharides in the Bowman layer. The presented changes underline the great variation of ocular disorders related to Alport syndrome. To our knowledge, this is one of the first reports describing histologic corneal findings in Alport syndrome. Only a few cases with accumulation of mucopolysaccharides in the Bowman layer have been described previously, none of them being associated with Alport syndrome. Besides, anterior corneal alterations and corneal clouding seem to be uncommon in patients suffering from Alport syndrome.

Corneal subbasal nerve fiber regeneration in myopic patients after laser in situ keratomileusis★

PubMed Central

Deng, Shijing; Wang, Mengmeng; Zhang, Fengju; Sun, Xuguang; Hou, Wenbo; Guo, Ning

2012-01-01

A total of 26 myopic patients (52 eyes) underwent laser in situ keratomileusis. In vivo confocal microscopy revealed that most of the regenerated corneal subbasal nerve fibers in the corneal flap originated from the stump of corneal subbasal nerve fibers outside the ablation zone and extended towards the center of the cornea in all patients. Meanwhile, new fibers were also found to directly regenerate from deep in the stroma in some cases. Approximately 94% of regenerated corneal subbasal nerve fibers (73/78 eyes) regrew vertically into the peripheral central 6-mm circle area 1 month after surgery, 78% (28/36 eyes) grew into the central 3–6 mm area at 2 months, and 23% into the central 3-mm circle area at 3 months. In addition, there was no significant difference in corneal subbasal nerve fiber regenerative capacity between the basic fibroblast growth factor group and the 20% (v/v) deproteinized extract of calf blood group. The majority of corneal subbasal nerve fiber regeneration occurred from the stump of corneal subbasal nerve fibers outside the corneal flap, and the remaining growth occurred deep within the stroma. PMID:25657693

Functions of ocular surface mucins in health and disease

PubMed Central

Mantelli, Flavio; Argüeso, Pablo

2009-01-01

Purpose of review The purpose of the present review is to describe new concepts on the role of mucins in the protection of corneal and conjunctival epithelia and to identify alterations of mucins in ocular surface diseases. Recent findings New evidence indicates that gel-forming and cell surface-associated mucins contribute differently to the protection of the ocular surface against allergens, pathogens, extracellular molecules, abrasive stress, and drying. Summary Mucins are high molecular weight glycoproteins characterized by their extensive O-glycosylation. Major mucins expressed by the ocular surface epithelia include cell surface-associated mucins MUC1, -4 and -16, and the gel-forming mucin MUC5AC. Recent advances using functional assays have allowed the examination of their roles in the protection of corneal and conjunctival epithelia. Alterations in mucin and mucin O-glycan biosynthesis in ocular surface disorders, including allergy, non-autoimmune dry eye, autoimmune dry eye, and infection, are presented. PMID:18769205

The Favorable Effect of Mesenchymal Stem Cell Treatment on the Antioxidant Protective Mechanism in the Corneal Epithelium and Renewal of Corneal Optical Properties Changed after Alkali Burns.

PubMed

Cejka, Cestmir; Holan, Vladimir; Trosan, Peter; Zajicova, Alena; Javorkova, Eliska; Cejkova, Jitka

2016-01-01

The aim of this study was to examine whether mesenchymal stem cells (MSCs) and/or corneal limbal epithelial stem cells (LSCs) influence restoration of an antioxidant protective mechanism in the corneal epithelium and renewal of corneal optical properties changed after alkali burns. The injured rabbit corneas (with 0.25 N NaOH) were untreated or treated with nanofiber scaffolds free of stem cells, with nanofiber scaffolds seeded with bone marrow MSCs (BM-MSCs), with adipose tissue MSCs (Ad-MSCs), or with LSCs. On day 15 following the injury, after BM-MSCs or LSCs nanofiber treatment (less after Ad-MSCs treatment) the expression of antioxidant enzymes was restored in the regenerated corneal epithelium and the expressions of matrix metalloproteinase 9 (MMP9), inducible nitric oxide synthase (iNOS), α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and vascular endothelial factor (VEGF) were low. The central corneal thickness (taken as an index of corneal hydration) increased after the injury and returned to levels before the injury. In injured untreated corneas the epithelium was absent and numerous cells revealed the expressions of iNOS, MMP9, α-SMA, TGF-β1, and VEGF. In conclusion, stem cell treatment accelerated regeneration of the corneal epithelium, restored the antioxidant protective mechanism, and renewed corneal optical properties.

Mitomycin C: a promising agent for the treatment of canine corneal scarring

PubMed Central

Gupta, Rangan; Yarnall, Benjamin W.; Giuliano, Elizabeth A.; Kanwar, Jagat R.; Buss, Dylan G.; Mohan, Rajiv R.

2012-01-01

Objective To evaluate the safety and efficacy of mitomycin C (MMC) in prevention of canine corneal scarring. Methods With an in vitro approach using healthy canine corneas, cultures of primary canine corneal fibroblasts or myofibroblasts were generated. Primary canine corneal fibroblasts were obtained by growing corneal buttons in minimal essential medium supplemented with 10% fetal bovine serum. Canine corneal myofibroblasts were produced by growing cultures in serum-free medium containing transforming growth factor β1 (1 ng/mL). Trypan blue assay and phase-contrast microscopy were used to evaluate the toxicity of three doses of MMC (0.002%, 0.02% and 0.04%). Real-time PCR, immunoblot, and immunocytochemistry techniques were used to determine MMC efficacy to inhibit markers of canine corneal scarring. Results A single 2-min treatment of 0.02% or less MMC did not alter canine corneal fibroblast or keratocyte phenotype, viability, or growth. The 0.02% dose substantially reduced myofibroblast formation (up to 67%; P < 0.001), as measured by the change in RNA and protein expression of fibrosis biomarkers (α-smooth muscle actin and F-actin). Conclusion This in vitro study suggests that a single 2-min 0.02% MMC treatment to the canine corneal keratocytes is safe and may be useful in decreasing canine corneal fibrous metaplasia. In vivo studies are warranted. PMID:21929607

Cyclodextrin Enhances Corneal Tolerability and Reduces Ocular Toxicity Caused by Diclofenac

PubMed Central

Abdelkader, Hamdy; Fathalla, Zeinab; Moharram, Hossam; Ali, Taha F. S.

2018-01-01

With advances in refractive surgery and demand for cataract removal and lens replacement, the ocular use of nonsteroidal anti-inflammatory drugs (NSAIDs) has increased. One of the most commonly used NSAIDs is diclofenac (Diclo). In this study, cyclodextrins (CDs), α-, β-, γ-, and HP-β-CDs, were investigated with in vitro irritation and in vivo ulceration models in rabbits to reduce Diclo toxicity. Diclo-, α-, β-, γ-, and HP-β-CD inclusion complexes were prepared and characterized and Diclo-CD complexes were evaluated for corneal permeation, red blood cell (RBCs) haemolysis, corneal opacity/permeability, and toxicity. Guest- (Diclo-) host (CD) solid inclusion complexes were formed only with β-, γ-, and HP-β-CDs. Amphipathic properties for Diclo were recorded and this surfactant-like functionality might contribute to the unwanted effects of Diclo on the surface of the eye. Contact angle and spreading coefficients were used to assess Diclo-CDs in solution. Reduction of ocular toxicity 3-fold to16-fold and comparable corneal permeability to free Diclo were recorded only with Diclo-γ-CD and Diclo-HP-β-CD complexes. These two complexes showed faster healing rates without scar formation compared with exposure to the Diclo solution and to untreated groups. This study also highlighted that Diclo-γ-CD and Diclo-HP-β-CD demonstrated fast healing without scar formation. PMID:29636847

The cuticular nature of corneal lenses in Drosophila melanogaster.

PubMed

Stahl, Aaron L; Charlton-Perkins, Mark; Buschbeck, Elke K; Cook, Tiffany A

2017-07-01

The dioptric visual system relies on precisely focusing lenses that project light onto a neural retina. While the proteins that constitute the lenses of many vertebrates are relatively well characterized, less is known about the proteins that constitute invertebrate lenses, especially the lens facets in insect compound eyes. To address this question, we used mass spectrophotometry to define the major proteins that comprise the corneal lenses from the adult Drosophila melanogaster compound eye. This led to the identification of four cuticular proteins: two previously identified lens proteins, drosocrystallin and retinin, and two newly identified proteins, Cpr66D and Cpr72Ec. To determine which ommatidial cells contribute each of these proteins to the lens, we conducted in situ hybridization at 50% pupal development, a key age for lens secretion. Our results confirm previous reports that drosocrystallin and retinin are expressed in the two primary corneagenous cells-cone cells and primary pigment cells. Cpr72Ec and Cpr66D, on the other hand, are more highly expressed in higher order interommatidial pigment cells. These data suggest that the complementary expression of cuticular proteins give rise to the center vs periphery of the corneal lens facet, possibly facilitating a refractive gradient that is known to reduce spherical aberration. Moreover, these studies provide a framework for future studies aimed at understanding the cuticular basis of corneal lens function in holometabolous insect eyes.

[Novel CHST6 compound heterozygous mutations cause macular corneal dystrophy in a Chinese family].

PubMed

Qi, Yan-hua; Dang, Xiu-hong; Su, Hong; Zhou, Nan; Liang, Ting; Wang, Zheng; Huang, Shang-zhi

2010-02-01

The aim of this study was to identify mutations of CHST6 gene in a Chinese family with macular corneal dystrophy (MCD) and to investigate the histopathological changes of MCD. Corneal button of the proband was obtained from penetrating keratoplasty for the treatment of severe corneal dystrophy. The sections and ultrathin sections of this specimen were examined under light microscope and transmission electron microscope (TEM). Genomic DNA was extracted from leukocytes in peripheral blood from the family members. The coding region of CHST6 was amplified by polymerase chain reaction (PCR). The PCR products were analyzed by direct sequencing and restriction enzyme digestion. Histochemical study revealed positive results of colloidal iron stain. TEM revealed enlargement of smooth endoplasmic reticulum and the presence of intracytoplasmic vacuoles. Two mutations, Q298X Y358H, were identified in exon 3 of CHST6. Three patients were compound heterozygotes of these two mutations. The C892T transversion occurred at codon 298 turned the codon of glutamine to a stop codon; the T1072C transversion occurred at codon 358 caused a missense mutation, tyrosine to histidine. All six unaffected family members were heterozygotes. These two mutations were not detected in any of the 100 control subjects. The novel compound heterozygous mutation results in loss of CHST6 function and causes the occurrence of MCD. This is the first report of this gene mutation.

Thermoelectrically controlled device for studies of temperature-induced corneal shrinkage

NASA Astrophysics Data System (ADS)

Borja, David; Manns, Fabrice; Fernandez, Viviana; Lamar, Peggy; Soederberg, Per G.; Parel, Jean-Marie A.

2002-06-01

The purpose of this study was to design and calibrate a device to measure the dynamics of thermal shrinkage in corneal and scleral strips. The apparatus consists of a thermoelectric cell controlled by a temperature controller designed to generate temperatures up to 90 degree(s)C in rectangular corneal strips; a copper cuvette filled with Dextran solution that holds the corneal strip and a displacement sensor that measures the change in length of the tissue during heat-induced shrinkage. The device was tested on corneal tissue from Florida Eye-Bank eyes that were cut into 2x4mm rectangular strips. Preliminary results indicate that our system can reproducibly create and accurately measure thermally induced corneal shrinkage. Shrinkage experiments will be used to optimize laser parameters for corneal shrinkage during laser thermokeratoplasty and laser scleral buckling.

[Core principles of treatment of corneal damage in patients with thyroid eye disease].

PubMed

Grusha, Y O; Ismailova, D S; Sherstneva, L V

To develop a therapeutic approach and to estimate the efficiency of complex treatment of corneal damage in patients with thyroid eye disease (TED). The study enrolled 44 patients (52 eyes) divided into 2 groups depending on the severity of corneal damage. Treatment of those with severe involvement included pathogenetic measures (pulse steroid therapy and/or radiation therapy) and surgery (orbital decompression, eyelid and corneal surgery). As the result of the treatment, orbital inflammation decreased and the state of the cornea improved in all patients. The treatment of corneal damage in patients with TED may differ depending on numerous factors, such as the severity of corneal damage and activity of orbital inflammation. Taking into account the potential danger of corneal involvement, one should make efforts to early detection and management of the risk factors.

Corneal biomechanical properties in thyroid eye disease.

PubMed

Karabulut, Gamze Ozturk; Kaynak, Pelin; Altan, Cıgdem; Ozturker, Can; Aksoy, Ebru Funda; Demirok, Ahmet; Yılmaz, Omer Faruk

2014-06-01

The purpose of this study is to investigate the effect of thyroid eye disease (TED) on the measurement of corneal biomechanical properties and the relationship between these parameters and disease manifestations. A total of 54 eyes of 27 individuals with TED and 52 eyes of 30 healthy control participants were enrolled. Thyroid ophthalmopathy activity was defined using the VISA (vision, inflammation, strabismus, and appearance/exposure) classification for TED. The intraocular pressure (IOP) measurement with Goldmann applanation tonometer (GAT), axial length (AL), keratometry, and central corneal thickness (CCT) measurements were taken from each patient. Corneal biomechanical properties, including corneal hysteresis (CH) and corneal resistance factor (CRF) and noncontact IOP measurements, Goldmann-correlated IOP (IOPg) and corneal-compensated IOP (IOPcc) were measured with the Ocular Response Analyzer (ORA) using the standard technique. Parameters such as best corrected visual acuity, axial length, central corneal thickness, and corneal curvature were not statistically significant between the two groups (p > 0.05). IOP measured with GAT was higher in participants with TED (p < 0.001). The CH of TED patients was significantly lower than that of the control group. There was no significant difference in the corneal resistance factor between groups. However, IOPg and IOPcc were significantly higher in TED patients. CH and VISA grading of TED patients showed a negative correlation (p = 0.007). In conclusion, TED affects the corneal biomechanical properties by decreasing CH. IOP with GAT and IOPg is found to be increased in these patients. As the severity of TED increases, CH decreases in these patients. Copyright © 2014. Published by Elsevier B.V.

Corneal surface temperature change as the mode of stimulation of the non-contact corneal aesthesiometer.

PubMed

Murphy, P J; Morgan, P B; Patel, S; Marshall, J

1999-05-01

The non-contact corneal aesthesiometer (NCCA) assesses corneal sensitivity by using a controlled pulse of air, directed at the corneal surface. The purpose of this paper was to investigate whether corneal surface temperature change was a component in the mode of stimulation. Thermocouple experiment: A simple model corneal surface was developed that was composed of a moistened circle of filter paper placed on a thermocouple and mounted on a glass slide. The temperature change produced by different stimulus pressures was measured for five different ambient temperatures. Thermal camera experiment: Using a thermal camera, the corneal surface temperature change was measured in nine young, healthy subjects after exposure to different stimulus air pulses. Pulse duration was set at 0.9 s but was varied in pressure from 0.5 to 3.5 millibars. Thermocouple experiment: An immediate drop in temperature was detected by the thermocouple as soon as the air flow was incident on the filter paper. A greater temperature change was produced by increasing the pressure of the incident air flow. A relationship was found and a calibration curve plotted. Thermal camera experiment: For each subject, a drop in surface temperature was detected at each stimulus pressure. Furthermore, as the stimulus pressure increased, the induced reduction in temperature also increased. A relationship was found and a calibration curve plotted. The NCCA air-pulse stimulus was capable of producing a localized temperature change on the corneal surface. The principal mode of corneal nerve stimulation, by the NCCA air pulse, was the rate of temperature change of the corneal surface.

Ocular forward light scattering and corneal backward light scattering in patients with dry eye.

PubMed

Koh, Shizuka; Maeda, Naoyuki; Ikeda, Chikako; Asonuma, Sanae; Mitamura, Hayato; Oie, Yoshinori; Soma, Takeshi; Tsujikawa, Motokazu; Kawasaki, Satoshi; Nishida, Kohji

2014-09-18

To evaluate ocular forward light scattering and corneal backward light scattering in patients with dry eye. Thirty-five eyes in 35 patients with dry eye and 20 eyes of 20 healthy control subjects were enrolled. The 35 dry eyes were classified into two groups according to whether superficial punctate keratopathy in the central 6-mm corneal zone (cSPK) was present or not. Ocular forward light scattering was quantified with a straylight meter. Corneal backward light scattering from the anterior, middle, and posterior corneal parts was assessed with a corneal densitometry program using the Scheimpflug imaging system. Both dry eye groups had significantly higher intraocular forward light scattering than the control group (both P<0.05). The dry eye group with cSPK had significantly higher values in anterior and total corneal backward light scattering than the other two groups. Moderate positive correlations were observed between the cSPK score and corneal backward light scattering from the anterior cornea (R=0.60, P<0.001) and corneal backward light scattering from the total cornea (R=0.54, P<0.001); however, no correlation was found between cSPK score and ocular forward light scattering (R=0.01, P=0.932). Ocular forward light scattering and corneal backward light scattering from the anterior cornea were greater in dry eyes than in normal eyes. Increased corneal backward light scattering in dry eye at least partially results from cSPK overlying the optical zone. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Comparison of corneal thickness after the instillation of topical anesthetics: proparacaine versus oxybuprocaine.

PubMed

Nam, Sang Min; Lee, Hyung Keun; Kim, Eung Kweon; Seo, Kyoung Yul

2006-01-01

To compare changes in human corneal thickness after the instillation of proparacaine with those after oxybuprocaine instillation with time over a period of 10 minutes. Eighteen healthy young participants were recruited. Proparacaine was used in the right eye and oxybuprocaine in the left. Right and left baseline corneal thicknesses were measured every 30 seconds for 10 minutes using a noncontact specular microscope by 1 observer. Baseline corneal thickness was defined as the average of all values taken over 10 minutes. Changes in corneal thickness were measured every 20 seconds for 10 minutes after the administration of 1 drop of 0.5% proparacaine onto the right cornea and 1 drop of 0.4% oxybuprocaine onto the left cornea. Mean baseline right cornea thickness was 531 +/- 45 microm, and that of the left cornea was 531 +/- 42 microm. The corneal thickness after proparacaine increased by 8.6 microm ( approximately 4.5-12.6 microm, 95% CI) and then returned to baseline within 80 seconds. Corneal thickness after applying oxybuprocaine increased by 7.7 microm (3.6-11.2 microm, 95% CI) and then returned to baseline within 80 seconds. There was a second transient increase about 5 minutes later after proparacaine instillation but no additional transient increase after oxybuprocaine instillation. Oxybuprocaine is similar to proparacaine in terms of the severity of its effect on corneal thickness. Corneal thickness instability may occur for 5 minutes after proparacaine administration. Changes in corneal thickness after topical anesthetic instillation should be considered when performing measurements for refractive surgery or central corneal thickness in glaucoma patients.

Exponential Decay Metrics of Topical Tetracaine Hydrochloride Administration Describe Corneal Anesthesia Properties Mechanistically.

PubMed

Ethington, Jason; Goldmeier, David; Gaynes, Bruce I

2017-03-01

To identify pharmacodynamic (PD) and pharmacokinetic (PK) metrics that aid in mechanistic understanding of dosage considerations for prolonged corneal anesthesia. A rabbit model using 0.5% tetracaine hydrochloride was used to induce corneal anesthesia in conjunction with Cochet-Bonnet anesthesiometry. Metrics were derived describing PD-PK parameters of the time-dependent domain of recovery in corneal sensitivity. Curve fitting used a 1-phase exponential dissociation paradigm assuming a 1-compartment PK model. Derivation of metrics including half-life and mean ligand residence time, tau (τ), was predicted by nonlinear regression. Bioavailability was determined by area under the curve of the dose-response relationship with varying drop volumes. Maximal corneal anesthesia maintained a plateau with a recovery inflection at the approximate time of predicted corneal drug half-life. PDs of recovery of corneal anesthesia were consistent with a first-order drug elimination rate. The mean ligand residence time (tau, τ) was 41.7 minutes, and half-life was 28.89 minutes. The mean estimated corneal elimination rate constant (ke) was 0.02402 minute. Duration of corneal anesthesia ranged from 55 to 58 minutes. There was no difference in time domain PD area under the curve between drop volumes. Use of a small drop volume of a topical anesthetic (as low as 11 μL) is bioequivalent to conventional drop size and seems to optimize dosing regiments with a little effect on ke. Prolongation of corneal anesthesia may therefore be best achieved with administration of small drop volumes at time intervals corresponding to the half-life of drug decay from the corneal compartment.

21 CFR 886.1450 - Corneal radius measuring device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Corneal radius measuring device. 886.1450 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1450 Corneal radius measuring device. (a) Identification. A corneal radius measuring device is an AC-powered device intended to measure...

Corneal iron ring after conductive keratoplasty.

PubMed

Kymionis, George D; Naoumidi, Tatiana L; Aslanides, Ioannis M; Pallikaris, Ioannis G

2003-08-01

To report formation of corneal iron ring deposits after conductive keratoplasty. Observational case report. Case report. A 54-year-old woman underwent conductive keratoplasty for hyperopia. One year after conductive keratoplasty, iron ring pattern pigmentation was detected at the corneal epithelium of both eyes. This is the first report of the appearance of corneal iron ring deposits following conductive keratoplasty treatment in a patient. It is suggested that alterations in tear film stability, resulting from conductive keratoplasty-induced changes in corneal curvature, constitute the contributory factor for these deposits.

Wakayama symposium: new therapies for modulation of epithelialization in corneal wound healing.

PubMed

Choi, Jun-Sub; Joo, Choun-Ki

2013-01-01

Many factors are involved in the corneal wound healing mechanism, including adhesion, migration, and proliferation of corneal epithelial cells. Abnormal corneal wound healing leads to corneal edema, neovascularization, scar formation, and poor vision. Three agents, 17β-estradiol, nicergoline, and β-glucan, have demonstrated positive effects on the wound healing response in laboratory experiments and may be of help in controlling wound healing in corneas that have suffered epithelial damage or have undergone refractive surgery. Copyright © 2013 Elsevier Inc. All rights reserved.

Mucin Deficiency Causes Functional and Structural Changes of the Ocular Surface

PubMed Central

Evans, Christopher; Rompala, Olivia J.; Zhu, Lingxiang; Wang, Mingwu; Chen, Yin

2012-01-01

MUC5AC is the most abundant gel-forming mucin in the ocular system. However, the specific function is unknown. In the present study, a Muc5ac knockout (KO) mouse model was subject to various physiological measurements as compared to its wide-type (WT) control. Interestingly, when KO mice were compared to WT mice, the mean tear break up time (TBUT) values were significantly lower and corneal fluorescein staining scores were significantly higher. But the tear volume was not changed. Despite the lack of Muc5ac expression in the conjunctiva of KO mice, Muc5b expression was significantly increased in these mice. Corneal opacification, varying in location and severity, was found in a few KO mice but not in WT mice. The present results suggest a significant difference in the quality, but not the quantity, of tear fluid in the KO mice compared to WT mice. Dry eye disease is multifactorial and therefore further evaluation of the varying components of the tear film, lacrimal unit and corneal structure of these KO mice may help elucidate the role of mucins in dry eye disease. Because Muc5ac knockout mice have clinical features of dry eye, this mouse model will be extremely useful for further studies regarding the pathophysiology of the ocular surface in dry eye in humans. PMID:23272068

Designing Hydrogel Adhesives for Corneal Wound Repair

PubMed Central

Grinstaff, Mark W.

2013-01-01

Today, corneal wounds are repaired using nylon sutures. Yet there are a number of complications associated with suturing the cornea, and thus there is interest in an adhesive to replace or supplement sutures in the repair of corneal wounds. We are designing and evaluating corneal adhesives prepared from dendrimers – single molecular weight, highly branched polymers. We have explored two strategies to form these ocular adhesives. The first involves a photocrosslinking reaction and the second uses a peptide ligation reactions to couple the individual dendrimers together to from the adhesive. These adhesives were successfully used to repair corneal perforations, close the flap produced in a LASIK procedure, and secure a corneal transplant. PMID:17889330

Molecular expression in transfected corneal endothelial cells

NASA Astrophysics Data System (ADS)

Wang, Fan; Miao, Zhuang; Lu, Chengwei; Hao, Jilong

2017-10-01

To investigate the capability of human corneal endothelial cells serving as immunological cells. Expression of HLA-DP, -DQ, -DR, CD40, CD80, and CD86 was determined by immunohistochemical methods. Meanwhile, purified peripheral blood mononuclear cells were cocultured with human corneal endothelial cells which were pre-treated with and without -IFN respectively, activation of lymphocytes was determined by FACS analysis. In coculture system, T lymphocyte was activated by corneal endothelial cells, HLA-DP, -DQ, -DR and CD40 expression were increased by - IFN induction. Costimulatory molecular CD80 was shown on the endothelial cells. Human corneal endothelial cells were assumed to be involved in the corneal transplantation rejection process as potential antigen presenting cells.

Two cases of corneal perforation after oral administration of nonsteroidal anti-inflammatory drugs: oral NSAID-induced corneal damage.

PubMed

Masuda, Ikuya; Matsuo, Toshihiko; Okamoto, Kazuo; Matsushita, Kyoko; Ohtsuki, Hiroshi

2010-01-01

To report 2 cases of corneal perforation associated with the use of oral nonsteroidal anti-inflammatory drugs (NSAIDs). In a 62-year-old woman and a 79-year-old woman, corneal perforation occurred after 7 days and 5 months of oral NSAIDs administration, respectively. After NSAIDs were discontinued, the cornea epithelialized and the anterior chamber formed within 14 and 10 days, respectively. It is well known that topical NSAIDs cause corneal perforation. Observations in the present cases suggest that the oral administration of NSAIDs may also cause corneal damage, and hence, medical professionals should consider the risk of damage to the cornea when administering these drugs orally.

Healed corneal ulcer with keloid formation.

PubMed

Alkatan, Hind M; Al-Arfaj, Khalid M; Hantera, Mohammed; Al-Kharashi, Soliman

2012-04-01

We are reporting a 34-year-old Arabic white female patient who presented with a white mass covering her left cornea following multiple ocular surgeries and healed corneal ulcer. The lesion obscured further view of the iris, pupil and lens. The patient underwent penetrating keratoplasty and the histopathologic study of the left corneal button showed epithelial hyperplasia, absent Bowman's layer and subepithelial fibrovascular proliferation. The histopathologic appearance was suggestive of a corneal keloid which was supported by further ultrastructural study. The corneal graft remained clear 6 months after surgery and the patient was satisfied with the visual outcome. Penetrating keratoplasty may be an effective surgical option for corneal keloids in young adult patients.

The hierarchical response of human corneal collagen to load.

PubMed

Bell, J S; Hayes, S; Whitford, C; Sanchez-Weatherby, J; Shebanova, O; Vergari, C; Winlove, C P; Terrill, N; Sorensen, T; Elsheikh, A; Meek, K M

2018-01-01

Fibrillar collagen in the human cornea is integral to its function as a transparent lens of precise curvature, and its arrangement is now well-characterised in the literature. While there has been considerable effort to incorporate fibrillar architecture into mechanical models of the cornea, the mechanical response of corneal collagen to small applied loads is not well understood. In this study the fibrillar and molecular response to tensile load was quantified using small and wide angle X-ray scattering (SAXS/WAXS), and digital image correlation (DIC) photography was used to calculate the local strain field that gave rise to the hierarchical changes. A molecular scattering model was used to calculate the tropocollagen tilt relative to the fibril axis and changes associated with applied strain. Changes were measured in the D-period, molecular tilt and the orientation and spacing of the fibrillar and molecular networks. These measurements were summarised into hierarchical deformation mechanisms, which were found to contribute at varying strains. The change in molecular tilt is indicative of a sub-fibrillar "spring-like" deformation mechanism, which was found to account for most of the applied strain under physiological and near-physiological loads. This deformation mechanism may play an important functional role in tissues rich in fibrils of high helical tilt, such as skin and cartilage. Collagen is the primary mediator of soft tissue biomechanics, and variations in its hierarchical structure convey the varying amounts of structural support necessary for organs to function normally. Here we have examined the structural response of corneal collagen to tensile load using X-rays to probe hierarchies ranging from molecular to fibrillar. We found a previously unreported deformation mechanism whereby molecules, which are helically arranged relative to the axis of their fibril, change in tilt akin to the manner in which a spring stretches. This "spring-like" mechanism accounts for a significant portion of the applied deformation at low strains (<3%). These findings will inform the future design of collagen-based artificial corneas being developed to address world-wide shortages of corneal donor tissue. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Thrombin-induced phosphorylation of the regulatory light chain of myosin II in cultured bovine corneal endothelial cells.

PubMed

Satpathy, M; Gallagher, P; Lizotte-Waniewski, M; Srinivas, S P

2004-10-01

Phosphorylation of the regulatory light chain of myosin II (referred to as myosin light chain or MLC) leads to a loss of barrier integrity in cellular monolayers by an increase in the contractility of the cortical actin cytoskeleton. This effect has been examined in corneal endothelial (CE) cells. Experiments were performed using cultured bovine CE cells (BCEC). MLC phosphorylation was induced by a thrombin-mediated activation of the proteinase-activated receptor-1 (PAR-1). Expression of MLC kinase (MLCK), a Ca2+/calmodulin-dependent protein kinase that phosphorylates MLC at its Ser-19 and Thr-18 residues, was determined by RT-PCR and Western blotting. Expression of PAR-1, RhoA, and Rho kinase-1 (effector of RhoA) was ascertained by RT-PCR. MLC phosphorylation was assessed by urea-glycerol gel electrophoresis followed by immunoblotting. The effects of Rho kinase-1 and PKC were characterized by using their selective inhibitors, Y-27632 and chelerythrine, respectively. Reorganization of the cytoskeleton was evaluated by the phalloidin staining of actin. [Ca2+]i was measured using Fura-2. The barrier integrity was assayed as permeability of BCEC monolayers to horseradish peroxidase (HRP; 44 kDa). RT-PCR showed expression of MLCK, PAR-1, Rho kinase-1, and RhoA. Western blotting indicated expression of the non-muscle and smooth muscle isoforms of MLCK. Exposure to thrombin induced an increase in [Ca2+]i with the peak unaffected by an absence of extracellular Ca2+. Pre-exposure to thrombin (2 U ml(-1); 2 min) led to mono- and di-phosphorylation of MLC. Under both basal conditions and in the presence of thrombin, MLC phosphorylation was prevented by chelerythrine (10 microm) and Y-27632 (<25 microm). Thrombin led to inter-endothelial gaps secondary to the disruption of the cortical actin cytoskeleton, which under resting conditions was organized as a perijunctional actomyosin ring (PAMR). These responses were blocked by pre-treatment with Y-27632. Thrombin also increased permeability to HRP, which was abolished by pre-treatment with Y-27632. Thrombin induces MLC phosphorylation in BCEC. The consequent increase in the contractility of the actin cytoskeleton produces a centripetal force resulting in inter-endothelial gaps and a breakdown of barrier integrity. These responses are PKC- and Rho kinase-dependent. [Ca2+]i increase, as well as sensitivity of the thrombin response to PKC and Rho kinase inhibitors, are consistent with the expression of PAR-1 receptors in BCEC. Thrombin-induced hyperpermeability is a model to investigate barrier dysfunction induced by MLC phosphorylation.

A new approach based on Machine Learning for predicting corneal curvature (K1) and astigmatism in patients with keratoconus after intracorneal ring implantation.

PubMed

Valdés-Mas, M A; Martín-Guerrero, J D; Rupérez, M J; Pastor, F; Dualde, C; Monserrat, C; Peris-Martínez, C

2014-08-01

Keratoconus (KC) is the most common type of corneal ectasia. A corneal transplantation was the treatment of choice until the last decade. However, intra-corneal ring implantation has become more and more common, and it is commonly used to treat KC thus avoiding a corneal transplantation. This work proposes a new approach based on Machine Learning to predict the vision gain of KC patients after ring implantation. That vision gain is assessed by means of the corneal curvature and the astigmatism. Different models were proposed; the best results were achieved by an artificial neural network based on the Multilayer Perceptron. The error provided by the best model was 0.97D of corneal curvature and 0.93D of astigmatism. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Assessing microstructures of the cornea with Gabor-domain optical coherence microscopy: pathway for corneal physiology and diseases.

PubMed

Tankam, Patrice; He, Zhiguo; Chu, Ying-Ju; Won, Jungeun; Canavesi, Cristina; Lepine, Thierry; Hindman, Holly B; Topham, David J; Gain, Philippe; Thuret, Gilles; Rolland, Jannick P

2015-03-15

Gabor-domain optical coherence microscopy (GD-OCM) was applied ex vivo in the investigation of corneal cells and their surrounding microstructures with particular attention to the corneal endothelium. Experiments using fresh pig eyeballs, excised human corneal buttons from patients with Fuchs' endothelial dystrophy (FED), and healthy donor corneas were conducted. Results show in a large field of view (1  mm×1  mm) high definition images of the different cell types and their surrounding microstructures through the full corneal thickness at both the central and peripheral locations of porcine corneas. Particularly, an image of the endothelial cells lining the bottom of the cornea is highlighted. As compared to healthy human corneas, the corneas of individuals with FED show characteristic microstructural alterations of the Descemet's membrane and increased size and number of keratocytes. The GD-OCM-based imaging system developed may constitute a novel tool for corneal imaging and disease diagnosis. Also, importantly, it may provide insights into the mechanism of corneal physiology and pathology, particularly in diseases of the corneal endothelium.

Asymmetric Corneal Flattening Effect After Small Incision Cataract Surgery.

PubMed

Alpins, Noel; Ong, James K Y; Stamatelatos, George

2016-08-01

To determine whether the flattening effect of corneal incisions differs between the right and left eye. A retrospective study of preoperative and postoperative corneal astigmatism was performed for patients who had bilateral cataract surgery by a right-handed surgeon. The change in corneal astigmatism was attributed to the 2.2-mm phacoemulsification incision, and the incisional flattening effect was calculated. The incisions were grouped by position on the eye and whether they were performed on the preoperative steep corneal meridian. A total of 1,298 eyes of 649 patients were evaluated. The flattening effect of temporal 2.2-mm incisions performed on the preoperative corneal steep meridian was different for right eyes (0.53 diopters [D]) and left eyes (0.34 D) (P = .017). The flattening effect of superior 2.2-mm incisions performed on the preoperative corneal steep meridian was equivalent in the two eyes. The flattening effect of a corneal incision may depend on whether it has been performed on the right or the left eye. [J Refract Surg. 2016;32(9):598-603.]. Copyright 2016, SLACK Incorporated.

Correlation between corneal and ambient temperature with particular focus on polar conditions.

PubMed

Slettedal, Jon Klokk; Ringvold, Amund

2015-08-01

To examine the relationship between human corneal and environmental temperature. An infrared camera was used to measure the corneal surface temperature in a group of healthy volunteers as well as in an experimental setting with donor corneas and an artificial anterior chamber, employing circulating saline at +37°C. Liquid nitrogen was used to obtain a very low temperature in the experimental setting. High ambient temperature measurements were performed in a sauna. In healthy volunteers, the cornea required at least 20-30 min to adapt to change in ambient temperature. The relationship between corneal and external temperature was relatively linear. At the two extremes, +83°C and -40°C, the corneal temperature was +42°C and +25.1°C, respectively. In the experimental setting, corneal temperature was +24.3°C at air temperature -40°C. A rather stable aqueous humour temperature of +37°C and high thermal conductivity of the corneal tissue prevent corneal frostbite even at extremely low ambient temperatures. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Analysis of corneal astigmatism before surgery in Chinese congenital ectopia lentis patients.

PubMed

Zhang, Yichi; Jin, Guangming; Young, Charlotte Aimee; Cao, Qianzhong; Lin, Junxiong; Lin, Jianqiang; Wang, Yiyao; Zheng, Danying

2018-04-26

Purpose This study aims to describe the characteristics of corneal astigmatism before surgery in congenital ectopia lentis (CEL) patients. Methods This retrospective study reviewed 306 CEL patients from 1st January 2006, to 31st December 2015. One eye was randomly selected from each patient when the patient had bilateral EL. The influence of sex, laterality, and Marfan syndrome on corneal astigmatism in different age subgroups was evaluated and compared. The correlation between age and corneal astigmatism was evaluated. Results Two hundred fifty-two eyes were included in this study. The mean corneal astigmatism of CEL patients was 2.00 ± 1.28 D. There was a statistical difference in corneal astigmatism between CEL eyes with and without Marfan syndrome. However, no statistical difference was found between male and female patients, or between the EL-affected eye and the unaffected eye in monocular EL patients. There was a positive correlation between age and corneal astigmatism in CEL eyes. Conclusions This study suggests that CEL patients' corneal astigmatism is higher in patients with Marfan syndrome, and corneal astigmatism of the CEL eye increases with age. Our results are useful for surgeons to make appropriate incision and intraocular lens (IOL) choices for patients, as well as a useful reference for designs of new IOLs.

Comparison of stromal corneal nerves between normal and keratoconus patients using confocal microscopy.

PubMed

Ramírez Fernández, M; Hernández Quintela, E; Naranjo Tackman, R

2014-08-01

To evaluate the differences in stromal corneal nerves between normal patients and keratoconus patients. A total of 140 eyes of 70 normal patients (group A) and 122 eyes of 87 keratoconus patients (group B) were examined with the confocal microscope, with a central scan of the total corneal thickness being taken. The morphology and thickness of the corneal stromal nerves were evaluated by using the Navis v. 3.5.0. software. Nerve thickness was obtained from the mean between the widest and the narrowest portions of each stromal nerve. Corneal stromal nerves were observed as irregular linear hyper-reflective structures with wide and narrow portions in all cases. Mean corneal stromal nerves thickness in group A was 5.7±1.7 (range from 3.3 to 10.4 μ), mean corneal stromal nerves thickness in group B was 7.2±1.9 (range from 3.5 to 12.0 μ). There was a statistical significant difference (P<.05) in stromal corneal nerves thickness between group A and group B. Stromal corneal nerves morphology was similar in both groups, but stromal nerves were thicker in keratoconus patients. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Effect of Viscous Agents on Corneal Density in Dry Eye Disease.

PubMed

Wegener, Alfred R; Meyer, Linda M; Schönfeld, Carl-Ludwig

2015-10-01

To investigate the effect of the viscous agents, hydroxypropyl methylcellulose (HPMC), carbomer, povidone, and a combination of HPMC and povidone on corneal density in patients with dry eye disease. In total, 98 eyes of 49 patients suffering from dry eye and 65 eyes of 33 healthy age-matched individuals were included in this prospective, randomized study. Corneal morphology was documented with Scheimpflug photography and corneal density was analyzed in 5 anatomical layers (epithelium, bowman membrane, stroma, descemet's membrane, and endothelium). Corneal density was evaluated for the active ingredients HPMC, carbomer, povidone, and a combination of HPMC and povidone as the viscous agents contained in the artificial tear formulations used by the dry eye patients. Data were compared to the age-matched healthy control group without medication. Corneal density in dry eye patients was reduced in all 5 anatomical layers compared to controls. Corneal density was highest and very close to control in patients treated with HPMC containing ocular lubricants. Patients treated with lubricants, including carbomer as the viscous agent displayed a significant reduction of corneal density in layers 1 and 2 compared to control. HPMC containing ocular lubricants can help to maintain physiological corneal density and may be beneficial in the treatment of dry eye disease.

A novel quantitative methodology for age evaluation of the human corneal endothelium

NASA Astrophysics Data System (ADS)

Rannou, Klervi; Thuret, Gilles; Gain, Philippe; Pinoli, Jean-Charles; Gavet, Yann

2017-03-01

The human corneal endothelium regulates the cornea transparency. Its cells, that cannot regenerate after birth, form a tesselated mosaic with almost perfect hexagonal cells during childhood, becoming progressively bigger and less ordered during aging. This study included 50 patients (in 10 decades groups) and 10 specular microscopy observations per patient. Five different criteria were measured on the manually segmented cells: area and perimeter of the cells as well as reduced Minkowski functionals. All these criteria were used to assess the probability of age group membership. We demonstrated that the age evaluation is near the reality, although a high variability was observed for patients between 30 and 70 years old.

New 223-nm excimer laser surgical system for photorefractive keratectomy

NASA Astrophysics Data System (ADS)

Bagaev, Sergei N.; Razhev, Alexander M.; Zhupikov, Andrey A.

1999-02-01

The using of KrCl (223 nm) excimer laser in ophthalmic devices for Photorefractive Keratectomy (PRK) and phototherapeutic Keratectomy (PTK) is offered. The structure and functions of a new surgical UV ophthalmic laser systems Medilex using ArF (193 nm) or KrCl (223 nm) excimer laser for corneal surgery are presented. The systems Medilex with the new optical delivery system is used for photoablative reprofiling of the cornea to correct refraction errors (myopia, hyperopia and astigmatism) and to treat a corneal pathologies. The use of the 223 nanometer laser is proposed to have advantages over the 193 nanometer laser. The results of application of the ophthalmic excimer laser systems Medilex for treatment of myopia are presented.

Slug is upregulated during wound healing and regulates cellular phenotypes in corneal epithelial cells.

PubMed

Aomatsu, Keiichi; Arao, Tokuzo; Abe, Kosuke; Kodama, Aya; Sugioka, Koji; Matsumoto, Kazuko; Kudo, Kanae; Kimura, Hideharu; Fujita, Yoshihiko; Hayashi, Hidetoshi; Nagai, Tomoyuki; Shimomura, Yoshikazu; Nishio, Kazuto

2012-02-16

The involvement of the epithelial mesenchymal transition (EMT) in the process of corneal wound healing remains largely unclear. The purpose of the present study was to gain insight into Slug expression and corneal wound healing. Slug expression during wound healing in the murine cornea was evaluated using fluorescence staining in vivo. Slug or Snail was stably introduced into human corneal epithelial cells (HCECs). These stable transfectants were evaluated for the induction of the EMT, cellular growth, migration activity, and expression changes in differentiation-related molecules. Slug, but not Snail, was clearly expressed in the nuclei of corneal epithelial cells in basal lesion of the corneal epithelium during wound healing in vivo. The overexpression of Slug or Snail induced an EMT-like cellular morphology and cadherin switching in HCECs, indicating that these transcription factors were able to mediate the typical EMT in HCECs. The overexpression of Slug or Snail suppressed cellular proliferation but enhanced the migration activity. Furthermore, ABCG2, TP63, and keratin 19, which are known as stemness-related molecules, were downregulated in these transfectants. It was found that Slug is upregulated during corneal wound healing in vivo. The overexpression of Slug mediated a change in the cellular phenotype affecting proliferation, migration, and expression levels of differentiation-related molecules. This is the first evidence that Slug is regulated during the process of corneal wound healing in the corneal epithelium in vivo, providing a novel insight into the EMT and Slug expression in corneal wound healing.

Ultra-high speed OCT allows measurement of intraocular pressure, corneal geometry, and corneal stiffness using a single instrument

NASA Astrophysics Data System (ADS)

Singh, Manmohan; Han, Zhaolong; Nair, Achuth; Schill, Alexander; Twa, Michael D.; Larin, Kirill V.

2018-02-01

Screening for ocular diseases, such as glaucoma and keratoconus, includes measuring the eye-globe intraocular pressure (IOP) and corneal biomechanical properties. However, currently available clinical tools cannot quantify corneal tissue material parameters, which can provide critical information for detecting diseases and evaluating therapeutic outcomes. Here, we demonstrate measurement of eye-globe IOP, corneal elasticity, and corneal geometry of in situ porcine corneas with a technique termed applanation optical coherence elastography (Appl-OCE) with single instrument. We utilize an ultrafast phase-sensitive optical coherence tomography system comprised of a 4X buffered Fourier domain mode-locked swept source laser with an Ascan rate of 1.5 MHz and a 7.3 kHz resonant scanner. The IOP was measured by imaging the response of in situ porcine corneas to a large force air-puff. As with other noncontact tonometers, the time when the cornea was applanated during the inwards and outwards motion was correlated to a measure air-pressure temporal profile. The IOP was also measured with a commercially available rebound tonometer for comparison. The stiffness of the corneas was assessed by directly imaging and analyzing the propagation of a focused micro air-pulse induced elastic wave, and the corneal geometry was obtained from the OCT structural image. Our results show that corneal thickness decreased as IOP increased, and that corneal stiffness increased with IOP. Moreover, the IOP measurements made by Appl-OCE were more closely correlated with the artificially set IOP than the rebound tonometer, demonstrating the capabilities of Appl-OCE to measure corneal stiffness, eye-globe IOP, and corneal geometry with a single instrument.

Central Corneal Thickness and its Relationship to Intra-Ocular and Epidmiological Determinants.

PubMed

Tayyab, Ali; Masrur, Amena; Afzal, Farooq; Iqbal, Fyza; Naseem, Kamran

2016-06-01

To measure central corneal thickness in Pakistani population and determine its relationship to intra-ocular pressure, age, gender and ethnicity. Cross-sectional observation study. Pakistan Institute of Medical Sciences, Islamabad, Pakistan, between December 2013 and February 2015. The right eyes of 1000 cases (496 males and 504 females) were recruited for this study. Inclusion criteria were Pashtun or Punjabi ethnicity, intra-ocular pressure < 22 mmHg, gonioscopically open angles, cup-disk-ratio < 0.5, and age matched normal visual fields. Cases with prior ocular surgery, contact lens use, corneal pathologies, myopia or hypermetropia > ±3.0 diopters, astigmatism of > ±1.0 diopters were excluded. Central corneal thickness was measured using a TopCon non-contact specular microscope. Intra-ocular pressure was measured using Goldmann applanation tonometer. Frequency distribution, test of significance, and regression analysis was carried out using Statistical Package for Social Sciences version 20.0. Mean age was 47.31 ±11.78 years. Ethnic composition was 51.6% (n=516) Pashtun and 48.4% (n=484) Punjabi. The mean central corneal thickness was 503.96 (±12.47) µm, while the mean intra-ocular pressure was 15.61 (±2.68) mmHg. Regression analysis showed a significant association between central corneal thickness and intra-ocular pressure (p=0.00) and age (p=0.00). A±100 µchange in central corneal thickness was associated with change in IOPof ±3.30 mmHg, whereas central corneal thickness decreased by 0.12 µm per year. No significant association could be established between central corneal thickness and ethnicity (p=0.19). Central corneal thickness of the studied races was comparable to non-Caucasians which affects intra-ocular pressure measurements, and decreases with increasing age. No relationship was observed between central corneal thickness and ethnicity or gender.

Effects of silicone hydrogel contact lenses on ocular surface after Sub-Bowman's Keratomileusis.

PubMed

Gao, Shaohui; Wu, Junshu; Li, Lili; Wang, Yong; Zhong, Xingwu

2013-11-01

To evaluate the efficacy of silicone hydrogel contact lenses on ocular surface after Sub-Bowman Keratomileusis (SBK). Forty-six patients suffered from myopia underwent a bilateral SBK. Post-operatively, one eye of each patient wore a PureVision contact lens for 24 h as a treated eye and the contralateral eye was as a blank control. Afterwards, corneal fluorescein (FL) staining, tear break-up time (TBUT), schirmer I test (SIT), central corneal thickness (CCT), ocular surface disease index (OSDI), corneal hysteresis (CH), corneal resistance factor (CRF) and corneal flap complications were assessed 1 d (except for CH and CRF), 1 week, 1 month and 3 months postoperatively. Following SBK, in contrast to the control, corneal fluorescein staining of treated eyes were significantly reduced and tear break-up time of treated eyes were significantly improved at 1 d and 1 week after SBK. However, Schirmer I test of treated and control eyes were not different after SBK. Central corneal thickness of treated eyes were significantly thinner than that of control at 1 d after SBK, however, there were no differences at other time points. Ocular surface disease index of treated eyes were obviously alleviated more than that of control at 1 d after SBK, but no differences were found at other visits. Moreover, Corneal hysteresis and corneal resistance factor of treated and un-treated eyes were not different after surgery. And also the rate of corneal flap complications were not different between treated and control eyes after SBK. Silicone hydrogel contact lenses played a positive role in accelerating corneal epithelial healing, enhancing tear film stability and reducing discomfort of patients in the early stage after SBK.

Short-term corneal changes with gas-permeable contact lens wear in keratoconus subjects: a comparison of two fitting approaches.

PubMed

Romero-Jiménez, Miguel; Santodomingo-Rubido, Jacinto; Flores-Rodríguez, Patricia; González-Méijome, Jose-Manuel

2015-01-01

To evaluate changes in anterior corneal topography and higher-order aberrations (HOA) after 14-days of rigid gas-permeable (RGP) contact lens (CL) wear in keratoconus subjects comparing two different fitting approaches. Thirty-one keratoconus subjects (50 eyes) without previous history of CL wear were recruited for the study. Subjects were randomly fitted to either an apical-touch or three-point-touch fitting approach. The lens' back optic zone radius (BOZR) was 0.4mm and 0.1mm flatter than the first definite apical clearance lens, respectively. Differences between the baseline and post-CL wear for steepest, flattest and average corneal power (ACP) readings, central corneal astigmatism (CCA), maximum tangential curvature (KTag), anterior corneal surface asphericity, anterior corneal surface HOA and thinnest corneal thickness measured with Pentacam were compared. A statistically significant flattening was found over time on the flattest and steepest simulated keratometry and ACP in apical-touch group (all p<0.01). A statistically significant reduction in KTag was found in both groups after contact lens wear (all p<0.05). Significant reduction was found over time in CCA (p=0.001) and anterior corneal asphericity in both groups (p<0.001). Thickness at the thinnest corneal point increased significantly after CL wear (p<0.0001). Coma-like and total HOA root mean square (RMS) error were significantly reduced following CL wearing in both fitting approaches (all p<0.05). Short-term rigid gas-permeable CL wear flattens the anterior cornea, increases the thinnest corneal thickness and reduces anterior surface HOA in keratoconus subjects. Apical-touch was associated with greater corneal flattening in comparison to three-point-touch lens wear. Copyright © 2014 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

Comparative quantitative assessment of the human corneal sub-basal nerve plexus by in vivo confocal microscopy and histological staining.

PubMed

Kowtharapu, B S; Winter, K; Marfurt, C; Allgeier, S; Köhler, B; Hovakimyan, M; Stahnke, T; Wree, A; Stachs, O; Guthoff, R F

2017-03-01

PurposeThis study was designed to compare and contrast quantitative data of the human corneal sub-basal nerve plexus (SBP) evaluated by two different methods: in vivo confocal microscopy (IVCM), and immunohistochemical staining of ex vivo donor corneas.MethodsSeven parameters of the SBP in large-scale IVCM mosaicking images from healthy subjects were compared with the identical parameters in ex vivo donor corneas stained by β-III-tubulin immunohistochemistry. Corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), average weighted corneal nerve fiber tortuosity (CNFTo), corneal nerve connection points (CNCP), average corneal nerve single-fiber length (CNSFL), and average weighted corneal nerve fiber thickness (CNFTh) were calculated using a dedicated, published algorithm and compared.ResultsOur experiments showed significantly higher values for CNFL (50.2 vs 21.4 mm/mm 2 ), CNFD (1358.8 vs 277.3 nerve fibers/mm 2 ), CNBD (847.6 vs 163.5 branches/mm 2 ), CNFTo (0.095 vs 0.081 μm -1 ), and CNCP (49.4 vs 21.6 connections/mm 2 ) in histologically staining specimens compared with IVCM images. In contrast, CNSFL values were higher in IVCM images than in histological specimens (32.1 vs 74.1 μm). No significant difference was observed in CNFTh (2.22 vs 2.20 μm) between the two groups.ConclusionsThe results of this study have shown that IVCM has an inherently lower resolution compared with ex vivo immunohistochemical staining of the corneal SBP and that this limitation leads to a systematic underestimation of several SBP parameters. Despite this shortcoming, IVCM is a vital clinical tool for in vivo characterization, quantitative clinical imaging, and evaluation of the human corneal SBP.

Effect of Topically Applied Azithromycin on Corneal Epithelial and Endothelial Apoptosis in a Rat Model of Corneal Alkali Burn.

PubMed

Arikan, Sedat; Karaca, Turan; Ertekin, Yusuf Haydar; Comez, Arzu Taskiran; Ersan, Ismail; Demirtas, Selim; Elmas, Sait; Tufan, Hasan Ali; Turkon, Hakan

2016-04-01

To investigate the antiapoptotic effect of topically administered azithromycin (AZM) on corneal epithelial and endothelial cells in a rat model of corneal alkali burn. Twenty-four Wistar albino rats were divided into 4 equal groups as pseudovehicle (group 1), control (group 2), alkali burned (group 3), and treatment (group 4) groups. Alkali injury was induced only in the right corneas of rats belonging to groups 3 and 4 using 1N NaOH. The rats in group 3 and the rats in group 4 were respectively treated either with an artificial tear gel or with 1.5% AZM eye drops for 5 days. At the fifth day of the experiment, the apoptosis in the corneal epithelium and endothelium of all rats was assessed using a terminal dUTP nick-end labeling (TUNEL) assay. In addition, tumor necrosis factor-alpha (TNF-α) density in the corneal epithelium was measured in all rats. The mean numbers of TUNEL+ cells in the corneal epithelium and endothelium of rats in group 3 were 117.1 ± 23.8 and 34.6.± 11.3, respectively, whereas in group 4, they were 75.8 ± 15.7 and 14.7 ± 3.5, respectively. Also the mean TNF-α densities in the corneal epithelium in group 3 and group 4 were 2.65 ± 1.3 and 1.65 ± 1.1, respectively. There was a significant decrease in the mean number of TUNEL+ cells in the corneal epithelium and endothelium and in the mean TNF-α density in the corneal epithelium of rats in group 4, when compared with group 3. Topically applied AZM can decrease TNF-α-induced apoptosis in corneal alkali burn.

Corneal endothelium: developmental strategies for regeneration

PubMed Central

Zavala, J; López Jaime, G R; Rodríguez Barrientos, C A; Valdez-Garcia, J

2013-01-01

The main treatment available for restoration of the corneal endothelium is keratoplasty. This procedure is faced with several difficulties, including the shortage of donor tissue, post-surgical complications associated with the use of drugs to prevent immune rejection, and a significant increase in the occurrence of glaucoma. Recently, surgical procedures such as Descemet's stripping endothelial keratoplasty have focused on the transplant of corneal endothelium, yielding better visual results but still facing the need for donor tissue. The emergent strategies in the field of cell biology and tissue cultivation of corneal endothelial cells aim at the production of transplantable endothelial cell sheets. Cell therapy focuses on the culture of corneal endothelial cells retrieved from the donor, in the donor's cornea, followed by transplantation into the recipient. Recently, research has focused on overcoming the challenge of harvesting human corneal endothelial cells and the generation of new biomembranes to be used as cell scaffolds in surgical procedures. The use of corneal endothelial precursors from the peripheral cornea has also demonstrated to be effective and represents a valuable tool for reducing the risk of rejection in allogeneic transplants. Several animal model reports also support the use of adult stem cells as therapy for corneal diseases. Current results represent important progresses in the development of new strategies based on alternative sources of tissue for the treatment of corneal endotheliopathies. Different databases were used to search literature: PubMed, Google Books, MD Consult, Google Scholar, Gene Cards, and NCBI Books. The main search terms used were: ‘cornea AND embryology AND transcription factors', ‘human endothelial keratoplasty AND risk factors', ‘(cornea OR corneal) AND (endothelium OR endothelial) AND cell culture', ‘mesenchymal stem cells AND cell therapy', ‘mesenchymal stem cells AND cornea', and ‘stem cells AND (cornea OR corneal) AND (endothelial OR endothelium)'. PMID:23470788

Quantitative OCT-based longitudinal evaluation of intracorneal ring segment implantation in keratoconus.

PubMed

Pérez-Merino, Pablo; Ortiz, Sergio; Alejandre, Nicolas; Jiménez-Alfaro, Ignacio; Marcos, Susana

2013-09-09

To characterize the geometrical properties of keratoconic corneas upon intracorneal ring segments (ICRS) implantation, using custom-developed optical coherence tomography (OCT). Ten keratoconic corneas were measured pre- and post-ICRS surgery (7, 30, and 90 days). Corneal topographic and pachymetric maps were obtained from three-dimensional (3D) images acquired with OCT, provided with custom algorithms for image analysis, distortion correction, and quantification. The 3D positioning of the ICRS was also estimated longitudinally, relative to the pupil center and iris plane. Preoperatively, the average corneal radii of curvature were 7.02 ± 0.54 mm (anterior) and 5.40 ± 0.77 mm (posterior), and the minimum corneal thickness was 384 ± 60 μm. At 90 days, the average corneal radii of curvature were 7.26 ± 0.53 mm (anterior) and 5.44 ± 0.71 mm (posterior), and the minimum corneal thickness was 396 ± 46 μm. ICRS implantation produced a significant decrease of corneal power (by 1.71 ± 1.83 diopters [D] at 90 days). Corneal irregularities (defined by high order Zernike terms of the corneal elevation maps) and the corneal thickness distribution decreased in some patients and increased in others. The 3D ICRS depth matched the planned ICRS depth well (within 23.93 ± 23.49 μm). On average, ICRS showed an overall tilt of -6.8 ± 2.6° (temporal) and -2.1 ± 0.8° (superior) at 7 days. Spectral OCT (sOCT) provided with distortion correction and analysis tools, is an excellent instrument for evaluating the changes produced by ICRS in keratoconic corneas, and for analyzing the 3D ICRS position during the follow up. ICRS produced flattening on the anterior corneal surface, although the benefit for corneal surface regularization varied across patients.

Instillation of Sericin Enhances Corneal Wound Healing through the ERK Pathway in Rat Debrided Corneal Epithelium

PubMed Central

Nagai, Noriaki; Fukuoka, Yuya; Ishii, Miyu; Otake, Hiroko; Yamamoto, Tetsushi; Taga, Atsushi; Okamoto, Norio; Shimomura, Yoshikazu

2018-01-01

Sericin is a major constituent of silk produced by silkworms. We previously found that the instillation of sericin enhanced the proliferation of corneal epithelial cells, and acted to promote corneal wound healing in both normal and diabetic model rats. However, the mechanisms by which sericin promotes the proliferation of corneal cells have not been established. In this study, we investigated the effects of sericin on Akt and ERK activation in a human corneal epithelial cell line (HCE-T cells) and rat debrided corneal epithelium. Although Akt phosphorylation was not detected following the treatment of HCE-T cells with sericin, ERK1/2 phosphorylation was enhanced. The growth of HCE-T cells treated with sericin was significantly increased, with the cell growth of sericin-treated HCE-T cells being 1.7-fold higher in comparison with vehicle-treated HCE-T cells. On the other hand, both of an ERK inhibitor U0126 (non-specific specific inhibitor) and SCH772984 (specific inhibitor) attenuated the enhanced cell growth by sericin, and the growth level in the case of co-treatment with sericin and ERK1/2 inhibitor was similar to that of cells treated with ERK1/2 inhibitor alone. In an in vivo study using rat debrided corneal epithelium, the corneal wound healing rate was enhanced by the instillation of sericin, and this enhancement was also attenuated by the instillation of U0126. In addition, the corneal wound healing rate in rats co-instilled with sericin and U0126 was similar to that following the instillation of U0126 alone. In conclusion, we found that the instillation of sericin enhanced cell proliferation via the activation of the MAPK/ERK pathway, resulting in the promotion of corneal wound healing in rat eyes. These findings provide significant information for designing further studies to develop potent corneal wound-healing drugs. PMID:29642540

Effects of chalazia on corneal astigmatism : Large-sized chalazia in middle upper eyelids compress the cornea and induce the corneal astigmatism.

PubMed

Jin, Ki Won; Shin, Young Joo; Hyon, Joon Young

2017-03-31

A chalazion is a common eyelid disease that causes eye morbidity due to inflammation and cosmetic disfigurement. Corneal topographic changes are important factors in corneal refractive surgery, intraocular lens power calculations for cataract surgery, and visual acuity assessments. However, the effects of chalazia on corneal astigmatism have not been thoroughly investigated. The changes in corneal astigmatism according to chalazion size and location is necessary for better outcome of ocular surgery. The aim of this study is to evaluate changes in corneal astigmatism according to chalazion size and location. In this cross-sectional study, a total of 44 eyes from 33 patients were included in the chalazion group and 70 eyes from 46 patients comprised the control group. Chalazia were classified according to location and size. An autokeratorefractometer (KR8100, Topcon; Japan) and a Galilei™ dual-Scheimpflug analyzer (Ziemer Group; Port, Switzerland) were utilized to evaluate corneal changes. Oblique astigmatism was greater in the chalazion group compared with the control group (p < 0.05). Astigmatism by simulated keratometry (simK), steep K by simK, total root mean square, second order aberration, oblique astigmatism, and vertical astigmatism were significantly greater in the upper eyelid group (p < 0.05). Astigmatism by simK, second order aberration, oblique astigmatism, and vertical astigmatism were significantly greater in the large-sized chalazion group (p < 0.05). Corneal wavefront aberration was the greatest in the upper eyelid chalazion group, whole area group, and large-sized chalazion group (p < 0.05). Large-sized chalazia in the whole upper eyelid should be treated in the early phase because they induced the greatest change in corneal topography. Chalazion should be treated before corneal topography is performed preoperatively and before the diagnosis of corneal diseases.

Influence of eye biometrics and corneal micro-structure on noncontact tonometry.

PubMed

Jesus, Danilo A; Majewska, Małgorzata; Krzyżanowska-Berkowska, Patrycja; Iskander, D Robert

2017-01-01

Tonometry is widely used as the main screening tool supporting glaucoma diagnosis. Still, its accuracy could be improved if full knowledge about the variation of the corneal biomechanical properties was available. In this study, Optical Coherence Tomography (OCT) speckle statistics are used to infer the organisation of the corneal micro-structure and hence, to analyse its influence on intraocular pressure (IOP) measurements. Fifty-six subjects were recruited for this prospective study. Macro and micro-structural corneal parameters as well as subject age were considered. Macro-structural analysis included the parameters that are associated with the ocular anatomy, such as central corneal thickness (CCT), corneal radius, axial length, anterior chamber depth and white-to-white corneal diameter. Micro-structural parameters which included OCT speckle statistics were related to the internal organisation of the corneal tissue and its physiological changes during lifetime. The corneal speckle obtained from OCT was modelled with the Generalised Gamma (GG) distribution that is characterised with a scale parameter and two shape parameters. In macro-structure analysis, only CCT showed a statistically significant correlation with IOP (R2 = 0.25, p<0.001). The scale parameter and the ratio of the shape parameters of GG distribution showed statistically significant correlation with IOP (R2 = 0.19, p<0.001 and R2 = 0.17, p<0.001, respectively). For the studied group, a weak, although significant correlation was found between age and IOP (R2 = 0.053, p = 0.04). Forward stepwise regression showed that CCT and the scale parameter of the Generalised Gamma distribution can be combined in a regression model (R2 = 0.39, p<0.001) to study the role of the corneal structure on IOP. We show, for the first time, that corneal micro-structure influences the IOP measurements obtained from noncontact tonometry. OCT speckle statistics can be employed to learn about the corneal micro-structure and hence, to further calibrate the IOP measurements.

Corneal donations in South Africa: A 15-year review.

PubMed

York, Nicholas J; Tinley, Christopher

2017-07-28

Corneal pathology is one of the leading causes of preventable blindness in South Africa (SA). A corneal transplant can restore or significantly improve vision in most cases. However, in SA there is a gross shortage of corneal tissue available to ophthalmologists. Little has been published describing the magnitude of the problem. To describe trends in the number of corneal donors per year in SA, the number of corneal transplants performed each year, the origin of donors, the allocation of corneas to the public or private sector, and the demographics of donors. This was a retrospective review of all corneal donations to SA eye banks over the 15-year period 1 January 2002 - 31 December 2016. There was a progressive year-on-year decline in corneal donors over the study period, from 565 per year in 2002 to 89 in 2016. As a direct result, there has been an 85.5% decrease in the number of corneal transplants performed per year using locally donated corneas, from 1 049 in 2002 to 152 in 2016. Of the donors, 48.8% originated from mortuaries, 39.0% from private hospitals and 12.2% from government hospitals; donors from mortuaries showed the most significant decline over the 15-year period, decreasing by 94.8%. Of donated corneas, 79.3% were allocated to the private sector and 21.7% to the public sector. Males comprised 69.1% of donors, while 77.2% were white, 14.0% coloured, 6.3% black and 2.5% Indian/Asian. Donor age demonstrated a bimodal peak at 25 and 55 years. The number of corneal donations in SA has declined markedly, causing the burden of corneal disease requiring transplantation to rise steadily. Population groups with a low donor rate may have cultural and other objections to corneal donation, which should be a major focus of future research and initiatives aimed at reversing the current trends.

Application of Corvis ST to evaluate the effect of femtosecond laser-assisted cataract surgery on corneal biomechanics.

PubMed

Wei, Yinjuan; Xu, Lingxiao; Song, Hui

2017-08-01

The aim of the present study was to evaluate the effects of femtosecond laser-assisted cataract surgery (FLACS) and phacoemulsification on corneal biomechanics using corneal visualization Scheimpflug technology. The medical records of 50 eyes from 50 patients who received phacoemulsification and intraocular lens implantation because of age-related factors between June 2014 and September 2014 were retrospectively analyzed. FLACS was used in 12 eyes (FLACS group), and conventional phacoemulsification in 38 eyes (PHACO group). The evaluation of corneal biomechanical parameters included the first/second applanation time (A-time1/A-time2), the first/second applanation length (A-length1/A-length2), corneal velocity during the first/second applanation moment (Vin/Vout), highest concavity time, highest concavity-radius (HC-radius), peak distance (PD), deformation amplitude (DA), central corneal thickness (CCT), and intraocular pressure (IOP). The differences in A-length1/A-length2, IOP, CCT, PD, and DA were significant in the PHACO group between those before, 1 week after, and 1 month after surgery. No significant differences in corneal biomechanical parameters were found between those at 1 month after surgery and before surgery. There were significant differences in IOP and CCT in the FLACS group between those before, 1 week after, and 1 month after surgery. There were no significant differences in the other corneal biomechanical parameters. No significant differences were found in corneal biomechanical parameters between those 1 month after surgery and before surgery. There were significant differences in A-length1/A-length2, CCT, PD, and DA between the two groups at 1 week after surgery. There were no significant differences in corneal biomechanical parameters between the two groups at 1 month after surgery. In conclusion, the effect of FLACS on corneal biomechanics is smaller than that of phacoemulsification. The corneal biomechanical parameters are restored to preoperative levels with the healing of the incision, and the reduction of swelling of the tissue near the incision.

Influence of eye biometrics and corneal micro-structure on noncontact tonometry

PubMed Central

Majewska, Małgorzata; Krzyżanowska-Berkowska, Patrycja; Iskander, D. Robert

2017-01-01

Purpose Tonometry is widely used as the main screening tool supporting glaucoma diagnosis. Still, its accuracy could be improved if full knowledge about the variation of the corneal biomechanical properties was available. In this study, Optical Coherence Tomography (OCT) speckle statistics are used to infer the organisation of the corneal micro-structure and hence, to analyse its influence on intraocular pressure (IOP) measurements. Methods Fifty-six subjects were recruited for this prospective study. Macro and micro-structural corneal parameters as well as subject age were considered. Macro-structural analysis included the parameters that are associated with the ocular anatomy, such as central corneal thickness (CCT), corneal radius, axial length, anterior chamber depth and white-to-white corneal diameter. Micro-structural parameters which included OCT speckle statistics were related to the internal organisation of the corneal tissue and its physiological changes during lifetime. The corneal speckle obtained from OCT was modelled with the Generalised Gamma (GG) distribution that is characterised with a scale parameter and two shape parameters. Results In macro-structure analysis, only CCT showed a statistically significant correlation with IOP (R2 = 0.25, p<0.001). The scale parameter and the ratio of the shape parameters of GG distribution showed statistically significant correlation with IOP (R2 = 0.19, p<0.001 and R2 = 0.17, p<0.001, respectively). For the studied group, a weak, although significant correlation was found between age and IOP (R2 = 0.053, p = 0.04). Forward stepwise regression showed that CCT and the scale parameter of the Generalised Gamma distribution can be combined in a regression model (R2 = 0.39, p<0.001) to study the role of the corneal structure on IOP. Conclusions We show, for the first time, that corneal micro-structure influences the IOP measurements obtained from noncontact tonometry. OCT speckle statistics can be employed to learn about the corneal micro-structure and hence, to further calibrate the IOP measurements. PMID:28472178

Corneal modeling for analysis of photorefractive keratectomy

NASA Astrophysics Data System (ADS)

Della Vecchia, Michael A.; Lamkin-Kennard, Kathleen

1997-05-01

Procedurally, excimer photorefractive keratectomy is based on the refractive correction of composite spherical and cylindrical ophthalmic errors of the entire eye. These refractive errors are inputted for correction at the corneal plane and for the properly controlled duration and location of laser energy. Topography is usually taken to correspondingly monitor spherical and cylindrical corneorefractive errors. While a corneal topographer provides surface morphologic information, the keratorefractive photoablation is based on the patient's spherical and cylindrical spectacle correction. Topography is at present not directly part of the procedural deterministic parameters. Examination of how corneal curvature at each of the keratometric reference loci affect the shape of the resultant corneal photoablated surface may enhance the accuracy of the desired correction. The objective of this study was to develop a methodology to utilize corneal topography for construction of models depicting pre- and post-operative keratomorphology for analysis of photorefractive keratectomy. Multiple types of models were developed then recreated in optical design software for examination of focal lengths and other optical characteristics. The corneal models were developed using data extracted from the TMS I corneal modeling system (Computed Anatomy, New York, NY). The TMS I does not allow for manipulation of data or differentiation of pre- and post-operative surfaces within its platform, thus models needed to be created for analysis. The data were imported into Matlab where 3D models, surface meshes, and contour plots were created. The data used to generate the models were pre- and post-operative curvatures, heights from the corneal apes, and x-y positions at 6400 locations on the corneal surface. Outlying non-contributory points were eliminated through statistical operations. Pre- and post- operative models were analyzed to obtain the resultant changes in the corneal surfaces during PRK. A sensitivity analysis of the corneal topography system was also performed. Ray tracings were performed using the height data and the optical design software Zemax (Focus Software, Inc., Tucson, AZ). Examining pre- and post-operative values of corneal surfaces may further the understanding of how areas of the cornea contribute toward desired visual correction. Gross resultant power across the corneal surface is used in PRK, however, understanding the contribution of each point to the average power may have important implications and prove to be significant for achieving projected surgical results.

Outcomes of Phacoemulsification Using Different Size of Clear Corneal Incision in Eyes with Previous Radial Keratotomy.

PubMed

Zhang, Jing Shang; Liu, Xue; Wang, Jin Da; Xiong, Ying; Li, Jing; Li, Xiao Xia; Zhao, Jing; You, Qi Sheng; Huang, Yao; Tsai, Frank; Baum, Larry; Jhanji, Vishal; Wan, Xiu Hua

2016-01-01

To evaluate visual outcomes and complications after phacoemulsification in eyes with cataract and previous radial keratotomy (RK) cuts using different sizes of clear corneal incisions. The study was a retrospective study. Thirty eyes with cataract and previous RK underwent phacoemulsification and intraocular lens (IOL) implantation. Among them 7 eyes had 8 RK cuts, 13 eyes had 12 RK cuts, and 10 eyes had 16 RK cuts. Phacoemulsification and IOL implantation were performed through a 2.0-3.2 mm clear corneal incision by a single surgeon. In the 8 RK cuts group, 3.2 mm clear corneal incisions were used in 4 eyes, and 3.0 mm clear corneal incisions were used in 3 eyes. In the 12 RK cuts group, 3.2 mm clear corneal incisions were used in 6 eyes, and 2.2 mm clear corneal incisions were used in 7 eyes. In the 16 RK cuts group, 3.2 mm clear corneal incisions were used in 5 eyes, and 2.0 mm clear corneal incisions were used in 5 eyes. Patients were followed up 1 day, 1 week, 1 month, 3 months, 6 months, 1 year, 2 years, and 3 years postoperatively and were examined for the dehiscence of RK cuts during or after the surgery, post-operative best-corrected visual acuity (BCVA), corneal astigmatism, corneal endothelial cell density and complications. Successful phacoemulsification with IOL implantation was performed in all eyes. No wound dehiscence was noted in any eyes with 8 or 12 RK cuts. Wound dehiscence was noted in 2 eyes with 16 RK cuts. The dehiscence of RK cuts was closed successfully by injecting an air bubble with or without viscoelastic agent into the anterior chamber at the end of surgery. During the follow-up, the cuts were well apposed in all eyes, and no new dehiscence of RK cuts was noted. At the last follow-up, mean BCVA (0.2 ± 0.18 logMAR) was better than preoperative BCVA(0.45±0.19 logMAR) (P < 0.001). There was no significant difference between the long-term preoperative and postoperative mean corneal astigmatism (P = 0.3). However, there was a significant reduction in postoperative corneal endothelial cell density (1866.5±773.9 / mm2 vs 2421.7±655.7 / mm2) (P < 0.001). Phacoemulsification and IOL implantation with clear corneal incisions in eyes with previous RK were associated with good surgical outcomes. Wound dehiscence was not specificaly related to the size of clear corneal incision during phacoemulsification in these eyes.

Corneal structure and transparency

PubMed Central

Meek, Keith M.; Knupp, Carlo

2015-01-01

The corneal stroma plays several pivotal roles within the eye. Optically, it is the main refracting lens and thus has to combine almost perfect transmission of visible light with precise shape, in order to focus incoming light. Furthermore, mechanically it has to be extremely tough to protect the inner contents of the eye. These functions are governed by its structure at all hierarchical levels. The basic principles of corneal structure and transparency have been known for some time, but in recent years X-ray scattering and other methods have revealed that the details of this structure are far more complex than previously thought and that the intricacy of the arrangement of the collagenous lamellae provides the shape and the mechanical properties of the tissue. At the molecular level, modern technologies and theoretical modelling have started to explain exactly how the collagen fibrils are arranged within the stromal lamellae and how proteoglycans maintain this ultrastructure. In this review we describe the current state of knowledge about the three-dimensional stromal architecture at the microscopic level, and about the control mechanisms at the nanoscopic level that lead to optical transparency. PMID:26145225

A fibrin sealant for perforated and preperforated corneal ulcers.

PubMed Central

Lagoutte, F M; Gauthier, L; Comte, P R

1989-01-01

Fibrin sealant is used to close perforated or preperforated corneal ulcers. In addition to the usual advantages of cyanoacrylates it is degraded physiologically and provides a good support for corneal healing. Corneal grafting can be avoided when contraindicated or postponed when conditions allow. This technique has been successful in nine eyes of eight patients. Images PMID:2804032

Clinical correlates of common corneal neovascular diseases: a literature review

PubMed Central

Abdelfattah, Nizar Saleh; Amgad, Mohamed; Zayed, Amira A; Salem, Hamdy; Elkhanany, Ahmed E; Hussein, Heba; Abd El-Baky, Nawal

2015-01-01

A large subset of corneal pathologies involves the formation of new blood and lymph vessels (neovascularization), leading to compromised visual acuity. This article aims to review the clinical causes and presentations of corneal neovascularization (CNV) by examining the mechanisms behind common CNV-related corneal pathologies, with a particular focus on herpes simplex stromal keratitis, contact lenses-induced keratitis and CNV secondary to keratoplasty. Moreover, we reviewed CNV in the context of different types of corneal transplantation and keratoprosthesis, and summarized the most relevant treatments available so far. PMID:25709930

Optical coherence tomography-based topography determination of corneal grafts in eye bank cultivation

NASA Astrophysics Data System (ADS)

Damian, Angela; Seitz, Berthold; Langenbucher, Achim; Eppig, Timo

2017-01-01

Vision loss due to corneal injuries or diseases can be treated by transplantation of human corneal grafts (keratoplasty). However, quality assurance in retrieving and cultivating the tissue transplants is confined to visual and microbiological testing. To identify previous refractive surgery or morphological alterations, an automatic, noncontact, sterile screening procedure is required. Twenty-three corneal grafts have been measured in organ culture with a clinical spectral-domain optical coherence tomographer. Employing a biconic surface fit with 10 degrees of freedom, the radii of curvature and conic constants could be estimated for the anterior and posterior corneal surfaces. Thereupon, central corneal thickness, refractive values, and astigmatism have been calculated. Clinical investigations are required to elaborate specific donor-host matching in the future.

Excimer laser phototherapeutic keratectomy for shield ulcers and corneal plaques in vernal keratoconjunctivitis.

PubMed

Cameron, J A; Antonios, S R; Badr, I A

1995-01-01

Shield-shaped corneal ulcers and corneal plaques in vernal keratoconjunctivitis are associated with delayed epithelial healing, as well as the risks of infectious keratitis and sterile stromal ulceration. Significant visual impairment due to scarring and irregular astigmatism may result from central corneal lesions. Three eyes with central corneal lesions resulting from vernal keratoconjunctivitis were treated by excimer laser after active vernal keratoconjunctivitis was controlled and inflammatory plaque overlying the shield ulcers was removed. All three eyes showed rapid reepithelialization within 1 week. Spectacle-corrected visual acuity of 20/30 or better was obtained in each eye. In selected patients, excimer laser phototherapeutic keratectomy may be a useful adjunct in the treatment of shield-shaped corneal ulcers and plaques in vernal keratoconjunctivitis.

Corneal-shaping electrode

DOEpatents

Doss, James D.; Hutson, Richard L.

1982-01-01

The disclosure relates to a circulating saline electrode for changing corneal shape in eyes. The electrode comprises a tubular nonconductive electrode housing having an annular expanded base which has a surface substantially matched to a subject corneal surface. A tubular conductive electrode connected to a radiofrequency generating source is disposed within the electrode housing and longitudinally aligned therewith. The electrode has a generally hemispherical head having at least one orifice. Saline solution is circulated through the apparatus and over the cornea to cool the corneal surface while radiofrequency electric current emitted from the electrode flows therefrom through the cornea to a second electrode, on the rear of the head. This current heats the deep corneal stroma and thereby effects corneal reshaping as a biological response to the heat.

Understanding Neuropathic Corneal Pain-Gaps and Current Therapeutic Approaches

PubMed Central

Goyal, Sunali; Hamrah, Pedram

2017-01-01

The richly innervated corneal tissue is one of the most powerful pain generator in the body. Corneal neuropathic pain results from dysfunctional nerves causing perceptions such as burning, stinging, eye-ache and pain. Various inflammatory diseases, neurological diseases, and surgical interventions can be the underlying cause of corneal neuropathic pain. Recent efforts have been made by the scientific community to elucidate the pathophysiology and neurobiology of pain resulting from initially protective physiological reflexes, to a more persistent chronic state. The goal of this clinical review is to briefly summarize the pathophysiology of neuropathic corneal pain, describe how to systematically approach the diagnosis of these patients, and finally summarizing our experience with current therapeutic approaches for the treatment of corneal neuropathic pain. PMID:26959131

Interpreting the corneal response to oxygen: Is there a basis for re-evaluating data from gas-goggle studies?

PubMed

Papas, Eric B; Sweeney, Deborah F

2016-10-01

When anoxia (0% oxygen) is created within a gas-tight goggle, ocular physiological responses, including corneal swelling, limbal hyperaemia and pH change, are known to vary, depending on the presence or absence of a low, oxygen transmissibility contact lens. A new theory is proposed to account for this discrepancy based on the concept of lid derived oxygen, whereby oxygen originating from the vascular plexus of the palpebral conjunctiva supplements that available to the ocular surface in an open, normally blinking eye, even when the surrounding gaseous atmosphere is anoxic. The effect of a lid derived contribution to corneal oxygenation was assessed by using existing experimental data to model open-eye, corneal swelling behavior as a function of atmospheric oxygen content, both with and without the presence of a contact lens. These models predict that under atmospheric anoxia, contact lens wear results in 13.2% corneal swelling compared with only 5.4% when the lens was absent. Lid derived oxygen acts to provide the ocular surface in the non-contact lens wearing, normally blinking, open-eye with up to 4.7% equivalent oxygen concentration, even within the anoxic environment of a nitrogen filled goggle. Correcting for lid derived oxygen eliminates previously observed discrepancies in corneal swelling behavior and harmonizes the models for the contact lens wearing and gas-goggle cases. On this basis it is proposed that true anoxia at the ocular surface cannot be achieved by atmospheric manipulation (i.e. a gas-goggle) alone but requires an additional presence, e.g. a low, oxygen transmissibility contact lens, to prevent access to oxygen from the eyelids. Data from previously conducted experiments in which the gas-goggle paradigm was used, may have been founded on underestimates of the real oxygen concentration acting on the ocular surface at the time and if so, will require re-interpretation. Future work in this area should consider if a correction for lid derived oxygen is necessary. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preparation of arginine-glycine-aspartic acid-modified biopolymeric nanoparticles containing epigalloccatechin-3-gallate for targeting vascular endothelial cells to inhibit corneal neovascularization.

PubMed

Chang, Che-Yi; Wang, Ming-Chen; Miyagawa, Takuya; Chen, Zhi-Yu; Lin, Feng-Huei; Chen, Ko-Hua; Liu, Guei-Sheung; Tseng, Ching-Li

2017-01-01

Neovascularization (NV) of the cornea can disrupt visual function, causing ocular diseases, including blindness. Therefore, treatment of corneal NV has a high public health impact. Epigalloccatechin-3-gallate (EGCG), presenting antiangiogenesis effects, was chosen as an inhibitor to treat human vascular endothelial cells for corneal NV treatment. An arginine-glycine-aspartic acid (RGD) peptide-hyaluronic acid (HA)-conjugated complex coating on the gelatin/EGCG self-assembly nanoparticles (GEH-RGD NPs) was synthesized for targeting the α v β 3 integrin on human umbilical vein endothelial cells (HUVECs) in this study, and a corneal NV mouse model was used to evaluate the therapeutic effect of this nanomedicine used as eyedrops. HA-RGD conjugation via COOH and amine groups was confirmed by 1 H-nuclear magnetic resonance and Fourier-transform infrared spectroscopy. The average diameter of GEH-RGD NPs was 168.87±22.5 nm with positive charge (19.7±2 mV), with an EGCG-loading efficiency up to 95%. Images of GEH-RGD NPs acquired from transmission electron microscopy showed a spherical shape and shell structure of about 200 nm. A slow-release pattern was observed in the nanoformulation at about 30% after 30 hours. Surface plasmon resonance confirmed that GEH-RGD NPs specifically bound to the integrin α v β 3 . In vitro cell-viability assay showed that GEH-RGD efficiently inhibited HUVEC proliferation at low EGCG concentrations (20 μg/mL) when compared with EGCG or non-RGD-modified NPs. Furthermore, GEH-RGD NPs significantly inhibited HUVEC migration down to 58%, lasting for 24 hours. In the corneal NV mouse model, fewer and thinner vessels were observed in the alkali-burned cornea after treatment with GEH-RGD NP eyedrops. Overall, this study indicates that GEH-RGD NPs were successfully developed and synthesized as an inhibitor of vascular endothelial cells with specific targeting capacity. Moreover, they can be used in eyedrops to inhibit angiogenesis in corneal NV mice.

Preparation of arginine–glycine–aspartic acid-modified biopolymeric nanoparticles containing epigalloccatechin-3-gallate for targeting vascular endothelial cells to inhibit corneal neovascularization

PubMed Central

Chang, Che-Yi; Wang, Ming-Chen; Miyagawa, Takuya; Chen, Zhi-Yu; Lin, Feng-Huei; Chen, Ko-Hua; Liu, Guei-Sheung; Tseng, Ching-Li

2017-01-01

Neovascularization (NV) of the cornea can disrupt visual function, causing ocular diseases, including blindness. Therefore, treatment of corneal NV has a high public health impact. Epigalloccatechin-3-gallate (EGCG), presenting antiangiogenesis effects, was chosen as an inhibitor to treat human vascular endothelial cells for corneal NV treatment. An arginine–glycine–aspartic acid (RGD) peptide–hyaluronic acid (HA)-conjugated complex coating on the gelatin/EGCG self-assembly nanoparticles (GEH-RGD NPs) was synthesized for targeting the αvβ3 integrin on human umbilical vein endothelial cells (HUVECs) in this study, and a corneal NV mouse model was used to evaluate the therapeutic effect of this nanomedicine used as eyedrops. HA-RGD conjugation via COOH and amine groups was confirmed by 1H-nuclear magnetic resonance and Fourier-transform infrared spectroscopy. The average diameter of GEH-RGD NPs was 168.87±22.5 nm with positive charge (19.7±2 mV), with an EGCG-loading efficiency up to 95%. Images of GEH-RGD NPs acquired from transmission electron microscopy showed a spherical shape and shell structure of about 200 nm. A slow-release pattern was observed in the nanoformulation at about 30% after 30 hours. Surface plasmon resonance confirmed that GEH-RGD NPs specifically bound to the integrin αvβ3. In vitro cell-viability assay showed that GEH-RGD efficiently inhibited HUVEC proliferation at low EGCG concentrations (20 μg/mL) when compared with EGCG or non-RGD-modified NPs. Furthermore, GEH-RGD NPs significantly inhibited HUVEC migration down to 58%, lasting for 24 hours. In the corneal NV mouse model, fewer and thinner vessels were observed in the alkali-burned cornea after treatment with GEH-RGD NP eyedrops. Overall, this study indicates that GEH-RGD NPs were successfully developed and synthesized as an inhibitor of vascular endothelial cells with specific targeting capacity. Moreover, they can be used in eyedrops to inhibit angiogenesis in corneal NV mice. PMID:28115846

Human SLC4A11-C functions as a DIDS-stimulatable H+(OH−) permeation pathway: partial correction of R109H mutant transport

PubMed Central

Kao, Liyo; Azimov, Rustam; Abuladze, Natalia; Newman, Debra

2014-01-01

The SLC4A11 gene mutations cause a variety of genetic corneal diseases, including congenital hereditary endothelial dystrophy 2 (CHED2), Harboyan syndrome, some cases of Fuchs' endothelial dystrophy (FECD), and possibly familial keratoconus. Three NH2-terminal variants of the human SLC4A11 gene, named SLC4A11-A, -B, and -C are known. The SLC4A11-B variant has been the focus of previous studies. Both the expression of the SLC4A11-C variant in the cornea and its functional properties have not been characterized, and therefore its potential pathophysiological role in corneal diseases remains to be explored. In the present study, we demonstrate that SLC4A11-C is the predominant SLC4A11 variant expressed in human corneal endothelial mRNA and that the transporter functions as an electrogenic H+(OH−) permeation pathway. Disulfonic stilbenes, including 4,4′-diisothiocyano-2,2′-stilbenedisulfonate (DIDS), 4,4′-diisothiocyanatodihydrostilbene-2,2′-disulfonate (H2DIDS), and 4-acetamido-4′-isothiocyanato-stilbene-2,2′-disulfonate (SITS), which are known to bind covalently, increased SLC4A11-C-mediated H+(OH−) flux by 150–200% without having a significant effect in mock-transfected cells. Noncovalently interacting 4,4′-diaminostilbene-2,2′-disulfonate (DADS) was without effect. We tested the efficacy of DIDS on the functionally impaired R109H mutant (SLC4A11-C numbering) that causes CHED2. DIDS (1 mM) increased H+(OH−) flux through the mutant transporter by ∼40–90%. These studies provide a basis for future testing of more specific chemically modified dilsulfonic stilbenes as potential therapeutic agents to improve the functional impairment of specific SLC4A11 mutant transporters. PMID:25394471

Ectropion

MedlinePlus

... lubricant) may ease dryness and keep the cornea moist. Ointment may be helpful when the eye can't ... to: Corneal abrasions Corneal ulcers Eye infections Corneal ulcers can cause vision ... Images Eye ...

Ocular lesions in canine mucopolysaccharidosis I and response to enzyme replacement therapy.

PubMed

Newkirk, Kim M; Atkins, Rosalie M; Dickson, Patti I; Rohrbach, Barton W; McEntee, Michael F

2011-07-11

Mucopolysaccharidosis I (MPS I) is an inherited metabolic disorder resulting from deficiency of α-L-iduronidase and lysosomal accumulation of glycosaminoglycans (GAG) in multiple tissues. Accumulation of GAG in corneal stromal cells causes corneal opacity and reduced vision. The purpose of this study was to determine the extent of ocular GAG accumulation and investigate the effectiveness of intravenous enzyme replacement therapy (ERT) on corneal GAG accumulation in dogs. Ocular tissues were obtained from 58 dogs with mucopolysaccharidosis I and four unaffected controls. Affected dogs received either low-dose ERT, high-dose ERT, or no treatment; some low-dose dogs also received intrathecal treatments. Histologic severity of corneal stromal GAG accumulation was scored. Accumulation of GAG was found in corneal stromal cells and scleral fibroblasts but not in corneal epithelium, endothelium, ciliary epithelium, choroid, retina, retinal pigment epithelium, or optic nerve. Corneal GAG accumulation increased in severity with increasing age. Although low-dose ERT did not significantly reduce corneal stromal GAG accumulation in comparison with untreated animals, high-dose ERT did result in significantly less GAG accumulation compared with the untreated dogs (adjusted P = 0.0143) or the low-dose ERT group (adjusted P = 0.0031). Intrathecal treatments did not significantly affect GAG accumulation. Dogs that began ERT shortly after birth also had significantly less (P < 0.0001) GAG accumulation in the corneal stroma than dogs with a later onset of treatment. These data suggest that high-dose, intravenous ERT is effective at preventing and/or clearing corneal stromal GAG accumulation, particularly if initiated early after birth.

Corneal Astigmatism Stability in Descemet Membrane Endothelial Keratoplasty for Fuchs Corneal Dystrophy.

PubMed

Yokogawa, Hideaki; Sanchez, P James; Mayko, Zachary M; Straiko, Michael D; Terry, Mark A

2016-07-01

To calculate the magnitude and angle of the shift in corneal astigmatism associated with Descemet membrane endothelial keratoplasty (DMEK) surgery to determine the feasibility of concurrent astigmatism correction at the time of DMEK triple procedures. Retrospective study. Forty-seven eyes that previously underwent the DMEK procedure for Fuchs endothelial corneal dystrophy and that had more than 1.0 diopter (D) of front corneal astigmatism preoperatively were identified. All DMEK surgeries used a clear corneal temporal incision of 3.2 mm. Surgically induced astigmatism (SIA) was evaluated 6 months postsurgery with vector analysis using Scheimpflug image reading. We did not find a difference between pre- and postoperative magnitude of front astigmatism (P = 0.88; paired t test). The magnitude of the SIA front surface was 0.77 ± 0.63 D (range, 0.10-3.14 D). The centroid vector of the SIA front surface was 0.14 at 89.3°. A hyperopic corneal power shift was noted in both the front surface by 0.26 ± 0.74 D (range, 0.45-3.05 D) (P = 0.018; paired t test) and back surface by 0.56 ± 0.55 D (range, 0.25-2.40 D) (P < 0.01; paired t test). DMEK surgery induces minimal amounts of corneal astigmatism that is a with-the-rule shift associated with a temporal clear corneal incision. The stability of these data from preop to postop supports the plausibility of incorporating astigmatism correction with the cautious use of toric intraocular lenses for patients with Fuchs corneal dystrophy and cataract.

Association of Electroencephalography (EEG) Power Spectra with Corneal Nerve Fiber Injury in Retinoblastoma Patients.

PubMed

Liu, Jianliang; Sun, Juanjuan; Diao, Yumei; Deng, Aijun

2016-09-04

BACKGROUND In our clinical experience we discovered that EEG band power may be correlated with corneal nerve injury in retinoblastoma patients. This study aimed to investigate biomarkers obtained from electroencephalography (EEG) recordings to reflect corneal nerve injury in retinoblastoma patients. MATERIAL AND METHODS Our study included 20 retinoblastoma patients treated at the Department of Ophthalmology, Affiliated Hospital of Weifang Medical University between 2010 and 2014. Twenty normal individuals were included in the control group. EEG activity was recorded continuously with 32 electrodes using standard EEG electrode placement for detecting EEG power. A cornea confocal microscope was used to examine corneal nerve injury in retinoblastoma patients and normal individuals. Spearman rank correlation analysis was used to analyze the correlation between corneal nerve injury and EEG power changes. The sensitivity and specificity of changed EEG power in diagnosis of corneal nerve injury were also analyzed. RESULTS The predominantly slow EEG oscillations changed gradually into faster waves in retinoblastoma patients. The EEG pattern in retinoblastoma patients was characterized by a distinct increase of delta (P<0.01) and significant decrease of theta power P<0.05). Corneal nerves were damaged in corneas of retinoblastoma patients. Corneal nerve injury was positively correlated with delta EEG spectra power and negatively correlated with theta EEG spectra power. The diagnostic sensitivity and specificity by compounding in the series were 60% and 67%, respectively. CONCLUSIONS Changes in delta and theta of EEG appear to be associated with occurrence of corneal nerve injury. Useful information can be provided for evaluating corneal nerve damage in retinoblastoma patients through analyzing EEG power bands.

Surgical therapies for corneal perforations: 10 years of cases in a tertiary referral hospital

PubMed Central

Yokogawa, Hideaki; Kobayashi, Akira; Yamazaki, Natsuko; Masaki, Toshinori; Sugiyama, Kazuhisa

2014-01-01

Purpose To report surgical therapies for corneal perforations in a tertiary referral hospital. Methods Thirty-one eyes of 31 patients (aged 62.4±18.3 years) with surgically treated corneal perforations from January 2002 to July 2013 were included in this study. Demographic data such as cause of corneal perforation, surgical procedures, and visual outcomes were retrospectively analyzed. Results The causes of corneal perforation (n=31) were divided into infectious (n=8, 26%) and noninfectious (n=23, 74%) categories. Infectious causes included fungal ulcer, herpetic stromal necrotizing keratitis, and bacterial ulcer. The causes of noninfectious keratopathy included corneal melting after removal of a metal foreign body, severe dry eye, lagophthalmos, canaliculitis, the oral anticancer drug S-1, keratoconus, rheumatoid arthritis, neurotrophic ulcer, atopic keratoconjunctivitis, and unknown causes. Initial surgical procedures included central large corneal graft (n=17), small corneal graft (n=7), and amniotic membrane transplantation (n=7). In two cases the perforation could not be sealed during the first surgical treatment and required subsequent procedures. All infectious keratitis required central large penetrating keratoplasty to obtain anatomical cure. In contrast, several surgical options were used for the treatment of noninfectious keratitis. After surgical treatment, anatomical cure was obtained in all cases. Mean postoperative best corrected visual acuity was better at 6 months (logMAR 1.3) than preoperatively (logMAR 1.8). Conclusion Surgical therapies for corneal perforations in our hospital included central large lamellar/penetrating keratoplasty, small peripheral patch graft, and amniotic membrane transplantation. All treatments were effective. Corneal perforation due to the oral anticancer drug S-1 is newly reported. PMID:25378903

Canine corneal epithelial cells possess a sustained proliferative capacity and generate a spontaneously derived cell line.

PubMed

Morita, Maresuke; Fujita, Naoki; Abe, Momoko; Hayashimoto, Koji; Nakagawa, Takayuki; Nishimura, Ryohei; Tsuzuki, Keiko

2018-06-01

We have previously reported characteristics of canine corneal epithelial cells in vitro and found that canine corneal epithelial cells could maintain their proliferative capacity even after continuous culture without the use of feeder cells and growth promoting additives. The objective of this study was to elucidate proliferative characteristics of canine corneal epithelial cells independent of feeder cells and growth promoting additives, with the aim of developing a spontaneously derived corneal epithelial cell line. Canine and rabbit corneal epithelial cells were harvested from the limbus and cultured with, or without, feeder cells and growth promoting additives, and both were passaged continuously until growth arrest. Canine corneal epithelial cells could proliferate independently, and could be passaged more times than rabbit cells. A canine corneal epithelial cell line, cCEpi, which could be passaged more than 100 times without using feeder cells and growth promoting additives, was established. cCEpi cells maintained a cell morphology close to the primary culture and expressed p63, cytokeratin 15 (K15), and K3. Although changes in colony morphology, shortening of the population doubling time and a heteroploid karyotype were observed, cCEpi was not tumorigenic. Stratified cell sheets cultured from cCEpi were morphologically and immunohistologically similar to sheets cultivated from early passage cells. In conclusion, canine corneal epithelial cells can proliferate independent of feeder cells and growth promoting additives. cCEpi maintains properties similar to normal corneal epithelial cells and could be a useful source for studies in cellular biology and for developing novel therapies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Central corneal thickness and related factors in an elderly American Chinese population.

PubMed

Wang, Dandan; Singh, Kuldev; Weinreb, Robert; Kempen, John; He, Mingguang; Lin, Shan

2011-07-01

To assess central corneal thickness and related factors in an elderly American Chinese population residing in San Francisco. Cross-sectional community based study. American Chinese aged 40 years and older were enrolled using random cluster sampling and volunteer screening in the Chinatown district of San Francisco. The following data were obtained: central corneal thickness by ultrasound pachymetry, intraocular pressure by Goldmann applanation tonometry, axial length by A-scan biometry, refractive status and corneal curvature by autorefractor. History of systemic and ocular diseases was collected via standard questionnaire. Central corneal thickness. Of 311 eligible subjects, 274 consented to study participation, and 228 phakic eyes were analyzed. Mean corneal thickness was 524.1 ± 31.1 µm, 545.5 ± 30.9 µm and 538.9 ± 31.8 µm in the sampling cluster, volunteer group and all subjects, respectively. A multiple linear regression model showed corneal thickness to be negatively associated with age (standardized regression coefficient [SRC] = -0.21; P = 0.016) and corneal curvature (SRC = -0.19; P = 0.018) but positively correlated with intraocular pressure (SRC = 0.20; P = 0.023). The distribution of central corneal thickness among this American Chinese population is similar to that reported in studies from East Asia. The independent factors associated with thinner corneas included older age, lower intraocular pressure and greater corneal curvature. While descendents of Chinese immigrants in America have, on average, thicker corneas than their ancestors, this phenomenon is potentially impacted by the level of intraocular pressure. © 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists.

Innate Immune Regulation of Serratia marcescens–Induced Corneal Inflammation and Infection

PubMed Central

Zhou, Rong; Zhang, Rui; Sun, Yan; Platt, Sean; Szczotka-Flynn, Loretta; Pearlman, Eric

2012-01-01

Purpose. Serratia marcescens is frequently isolated from lenses of patients with contact lens-associated corneal infiltrates. In the current study, we examined the role of toll-like receptors (TLRs) and interleukin-1 receptor type 1 (IL-1R1) in S. marcescens–induced corneal inflammation and infection. Methods. The central corneal epithelium of C57BL/6 and gene knockout mice was abraded, and 1 × 107 S. marcescens were added in the presence of a silicone hydrogel contact lens, and we examined corneal inflammation by confocal microscopy and neutrophil enumeration. Viable bacteria were quantified by colony-forming units (CFU). Results. S. marcescens induced neutrophil recruitment to the corneal stroma, and increased corneal thickness and haze in C57BL/6 mice. Conversely, CFU was significantly lower by 48 hours post infection. In contrast, MyD88−/−, IL-1R−/−, TLR4−/−, and TLR4/5−/− corneas infected with S. marcescens had significantly increased CFU, indicating impaired clearance. However, there was no significant difference in CFU among C57BL/6, TIRAP−/−, and TRIF−/− mice. Tobramycin-killed S. marcescens induced corneal inflammation in C57BL/6 mice, which was impaired significantly in MD-2−/− mice and in C57BL/6 mice pretreated topically with the MD-2 antagonist eritoran tetrasodium. Conclusions. S. marcescens induces corneal inflammation by activation of TLR4/MD-2/MyD88 and the IL-1R1/MyD88 pathways, which are potential therapeutic targets for inhibition of S. marcescens-induced corneal inflammation. PMID:23033384

Pilot Study for OCT Guided Design and Fit of a Prosthetic Device for Treatment of Corneal Disease.

PubMed

Le, Hong-Gam T; Tang, Maolong; Ridges, Ryan; Huang, David; Jacobs, Deborah S

2012-01-01

Purpose. To assess optical coherence tomography (OCT) for guiding design and fit of a prosthetic device for corneal disease. Methods. A prototype time domain OCT scanner was used to image the anterior segment of patients fitted with large diameter (18.5-20 mm) prosthetic devices for corneal disease. OCT images were processed and analyzed to characterize corneal diameter, corneal sagittal height, scleral sagittal height, scleral toricity, and alignment of device. Within-subject variance of OCT-measured parameters was evaluated. OCT-measured parameters were compared with device parameters for each eye fitted. OCT image correspondence with ocular alignment and clinical fit was assessed. Results. Six eyes in 5 patients were studied. OCT measurement of corneal diameter (coefficient of variation, CV = 0.76%), cornea sagittal height (CV = 2.06%), and scleral sagittal height (CV = 3.39%) is highly repeatable within each subject. OCT image-derived measurements reveal strong correlation between corneal sagittal height and device corneal height (r = 0.975) and modest correlation between scleral and on-eye device toricity (r = 0.581). Qualitative assessment of a fitted device on OCT montages reveals correspondence with slit lamp images and clinical assessment of fit. Conclusions. OCT imaging of the anterior segment is suitable for custom design and fit of large diameter (18.5-20 mm) prosthetic devices used in the treatment of corneal disease.

Corneal changes with accommodation using dual Scheimpflug photography.

PubMed

Sisó-Fuertes, Irene; Domínguez-Vicent, Alberto; del Águila-Carrasco, Antonio; Ferrer-Blasco, Teresa; Montés-Micó, Robert

2015-05-01

To assess whether corneal parameters and aberrations are affected by accommodation. Optics Department, University of Valencia, Valencia, Spain. Prospective cross-sectional study. The Galilei G4 dual Scheimpflug device was used to obtain data on the anterior and posterior axial curvatures, total corneal power (TCP), and corneal pachymetry from 3 corneal zones (central: 0.0 up to 4.0 mm; paracentral or mid: 4.0 up to 7.0 mm; peripheral: 7.0 up to 10.0 mm) in young emmetropic eyes in the unaccommodated and 4 accommodated states (from -1.0 to -4.0 diopters [D] in 1.0 D steps). The 2nd-, 3rd-, and 4th-order aberrations as well as the root mean square (RMS) were also determined for the entire cornea at the same accommodative demands. The study evaluated 7 subjects (12 eyes). No significant changes in any measured parameter were found during accommodation for any corneal zone (P > .05). Statistically significant differences were found in the various corneal zones when it was assumed they were constant with accommodation (P < .01). A stable linear trend with accommodation was also found for corneal aberrations, although individual variations existed because of the high standard deviation values. Different parameters in various zones of the cornea as well as corneal aberrations were stable during accommodation. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

OPTICS OF CONDUCTIVE KERATOPLASTY: IMPLICATIONS FOR PRESBYOPIA MANAGEMENT

PubMed Central

Hersh, Peter S

2005-01-01

Purpose To define the corneal optics of conductive keratoplasty (CK) and assess the clinical implications for hyperopia and presbyopia management. Methods Four analyses were done. (1) Multifocal effects: In a prospective study of CK, uncorrected visual acuity (UCVA) for a given refractive error in 72 postoperative eyes was compared to control eyes. (2) Surgically induced astigmatism (SIA): 203 eyes were analyzed for magnitude and axis of SIA. (3) Higher-order optical aberrations: Corneal higher-order optical aberrations were assessed for 36 eyes after CK and a similar patient population after hyperopic laser in situ keratomileusis (LASIK). (4) Presbyopia clinical trial: Visual acuity, refractive result, and patient questionnaires were analyzed for 150 subjects in a prospective, multicenter clinical trial of presbyopia management with CK. Results (1) 63% and 82% of eyes after CK had better UCVA at distance and near, respectively, than controls. (2) The mean SIA was 0.23 diopter (D) steepening at 175° (P < .001); mean magnitude was 0.66 D (SD, 0.43 D). (3) After CK, composite fourth- and sixth-order spherical aberration increased; change in (Z12) spherical aberration alone was not statistically significant. When compared to hyperopic LASIK, there was a statistically significant increase in composite fourth- and sixth-order spherical aberration (P < .01) and spherical aberration (Z12) alone (P < .02); spherical aberration change was more prolate after CK. (4) After the CK monovision procedure, 80% of patients had J3 or better binocular UCVA at near; 84% of patients were satisfied. Satisfaction was associated with near UCVA of J3 or better in the monovision eye (P = .001) and subjectively good postoperative depth perception (P = .038). Conclusions CK seems to produce functional corneal multifocality with definable introduction of SIA and higher-order optical aberrations, and development of a more prolate corneal contour. These optical factors may militate toward improved near vision function. PMID:17057812

Risk factors for low vision related functioning in the Mycotic Ulcer Treatment Trial: a randomised trial comparing natamycin with voriconazole.

PubMed

Rose-Nussbaumer, Jennifer; Prajna, N Venkatesh; Krishnan, Tiruvengada; Mascarenhas, Jeena; Rajaraman, Revathi; Srinivasan, Muthiah; Raghavan, Anita; Oldenburg, Catherine E; O'Brien, Kieran S; Ray, Kathryn J; Porco, Travis C; McLeod, Stephen D; Acharya, Nisha R; Keenan, Jeremy D; Lietman, Thomas M

2016-07-01

The Mycotic Ulcer Treatment Trial I (MUTT I) was a double-masked, multicentre, randomised controlled trial, which found that topical natamycin is superior to voriconazole for the treatment of filamentous fungal corneal ulcers. In this study, we determine risk factors for low vision-related quality of life in patients with fungal keratitis. The Indian visual function questionnaire (IND-VFQ) was administered to MUTT I study participants at 3 months. Associations between patient and ulcer characteristics and IND-VFQ subscale score were assessed using generalised estimating equations. 323 patients were enrolled in the trial, and 292 (90.4%) completed the IND-VFQ at 3 months. Out of a total possible score of 100, the average VFQ score for all participants was 81.3 (range 0-100, SD 23.6). After correcting for treatment arm, each logMAR line of worse baseline visual acuity in the affected eye resulted in an average 1.2 points decrease on VFQ at 3 months (95% CI -1.8 to 0.6, p<0.001). Those who required therapeutic penetrating keratoplasty had an average of 25.2 points decrease on VFQ after correcting for treatment arm (95% CI -31.8 to -18.5, p<0.001). Study participants who were unemployed had on average 28.5 points decrease on VFQ (95% CI -46.9 to -10.2, p=0.002) after correcting for treatment arm. Monocular vision loss from corneal opacity due to fungal keratitis reduced vision-related quality of life. Given the relatively high worldwide burden of corneal opacity, improving treatment outcomes of corneal infections should be a public health priority. Clinicaltrials.gov Identifier: NCT00996736. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

In Vivo Assessment of Mechanisms Controlling Corneal Hydration.

DTIC Science & Technology

1986-01-01

12 Chapter 3. CORNEAL RESPONSE TO HYPOXIA INDUCED WITH RIGID AND HYDROGEL LENSES WORN DURING EYE CLOSURE 3.1 Summary...thickness vs time (recovery) following lens removal ................................ 28 | ~,.4 3.3 Change in corneal thickness vs hydrogel lens oxygen...transmissibility for closed eye wear ......... 30 3.4 Change in corneal thickness and oxygen under the lens vs rigid and hydrogel lens oxygen

Corneal Opacity in Domestic Ducks Experimentally Infected With H5N1 Highly Pathogenic Avian Influenza Virus.

PubMed

Yamamoto, Y; Nakamura, K; Yamada, M; Mase, M

2016-01-01

Domestic ducks can be a key factor in the regional spread of H5N1 highly pathogenic avian influenza (HPAI) virus in Asia. The authors performed experimental infections to examine the relationship between corneal opacity and H5N1 HPAI virus infection in domestic ducks (Anas platyrhyncha var domestica). A total of 99 domestic ducks, including 3 control birds, were used in the study. In experiment 1, when domestic ducks were inoculated intranasally with 2 H5N1 HPAI viruses, corneal opacity appeared more frequently than neurologic signs and mortality. Corneal ulceration and exophthalmos were rare findings. Histopathologic examinations of the eyes of domestic ducks in experiment 2 revealed that corneal opacity was due to the loss of corneal endothelial cells and subsequent keratitis with edema. Influenza viral antigen was detected in corneal endothelial cells and some other ocular cells by immunohistochemistry. Results suggest that corneal opacity is a characteristic and frequent finding in domestic ducks infected with the H5N1 HPAI virus. Confirming this ocular change may improve the detection rate of infected domestic ducks in the field. © The Author(s) 2015.

Corneal refractive surgery: Is intracorneal the way to go and what are the needs for technology?

NASA Astrophysics Data System (ADS)

Hjortdal, Jesper; Ivarsen, Anders

2014-02-01

Corneal refractive surgery aims to reduce or eliminate refractive errors of the eye by changing the refractive power of the cornea. For the last 20 years controlled excimer laser ablation of corneal tissue, either directly from the corneal stromal surface or from the corneal interior after creation of a superficial corneal flap has become widely used to correct myopia, hyperopia, and astigmatism. Recently, an intrastromal refractive procedure whereby a tissue lenticule is cut free in the corneal stroma by a femtosecond laser and removed through a small peripheral incision has been introduced. This procedure avoids creation of a corneal flap and the potential associated risks while avoiding the slow visual recovery of surface ablation procedures. Precise intrastromal femtosecond laser cutting of the fine lenticule requires very controlled laser energy delivery in order to avoid lenticule irregularities, which would compromise the refractive result and visual acuity. This newly introduced all-femtosecond based flap-free intracorneal refractive procedure has been documented to be a predictable, efficient, and safe procedure for correction of myopia and astigmatism. Technological developments related to further improved cutting quality, hyperopic and individualized treatments are desirable.

Corneal Biomechanics in Ectatic Diseases: Refractive Surgery Implications

PubMed Central

Ambrósio, Jr, Renato; Correia, Fernando Faria; Lopes, Bernardo; Salomão, Marcella Q.; Luz, Allan; Dawson, Daniel G.; Elsheikh, Ahmed; Vinciguerra, Riccardo; Vinciguerra, Paolo; Roberts, Cynthia J.

2017-01-01

Background: Ectasia development occurs due to a chronic corneal biomechanical decompensation or weakness, resulting in stromal thinning and corneal protrusion. This leads to corneal steepening, increase in astigmatism, and irregularity. In corneal refractive surgery, the detection of mild forms of ectasia pre-operatively is essential to avoid post-operative progressive ectasia, which also depends on the impact of the procedure on the cornea. Method: The advent of 3D tomography is proven as a significant advancement to further characterize corneal shape beyond front surface topography, which is still relevant. While screening tests for ectasia had been limited to corneal shape (geometry) assessment, clinical biomechanical assessment has been possible since the introduction of the Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, USA) in 2005 and the Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany) in 2010. Direct clinical biomechanical evaluation is recognized as paramount, especially in detection of mild ectatic cases and characterization of the susceptibility for ectasia progression for any cornea. Conclusions: The purpose of this review is to describe the current state of clinical evaluation of corneal biomechanics, focusing on the most recent advances of commercially available instruments and also on future developments, such as Brillouin microscopy. PMID:28932334

Prevalence and causes of corneal blindness.

PubMed

Wang, Haijing; Zhang, Yaoguang; Li, Zhijian; Wang, Tiebin; Liu, Ping

2014-04-01

The study aimed to assess the prevalence and causes of corneal blindness in a rural northern Chinese population. Cross-sectional study. The cluster random sampling method was used to select the sample. This population-based study included 11 787 participants of all ages in rural Heilongjiang Province, China. These participants underwent a detailed interview and eye examination that included the measurement of visual acuity, slit-lamp biomicroscopy and direct ophthalmoscopy. An eye was considered to have corneal blindness if the visual acuity was <9/18 because of corneal diseases. The main outcome measure was prevalence rates of corneal blindness and low vision. Among the 10 384 people enrolled in the study, the prevalence of corneal blindness is 0.3% (95% confidence interval 0.2-0.4%). The leading cause was keratitis in childhood (40.0%), followed by ocular trauma (33.3%) and keratitis in adulthood (20.0%). Age and illiteracy were found to be associated with an increased prevalence of corneal blindness. Blindness because of corneal diseases in rural areas of Northern China is a significant public health problem that needs to be given more attention. © 2013 Royal Australian and New Zealand College of Ophthalmologists.

Corneal transplantation trends in France from 2004 to 2015: A 12-year review.

PubMed

Bigan, Guillaume; Puyraveau, Marc; Saleh, Maher; Gain, Philippe; Martinache, Isabelle; Delbosc, Bernard; Gauthier, Anne-Sophie

2018-04-01

The aim of this study was to report the 12-year longitudinal trends in indication and corneal transplantation techniques in France from 2004 to 2015. The records of all corneal transplantations performed from 2004 to 2015 in France were retrospectively reviewed. The patient indications and types of transplant performed were analyzed. A total of 46,658 corneal transplantations were performed between 2004 and 2015, with 34,187 (73.3%) penetrating keratoplasty and 10,452 (22.4%) lamellar keratoplasty. The leading surgical indications were secondary endothelial failure (24.3%), keratoconus (18.8%), regraft (13.5%), and Fuchs endothelial corneal dystrophy (15.1%). Endothelial keratoplasty became the preferred technique for endothelial diseases and deep anterior lamellar keratoplasty the preferred technique for keratoconus, surpassing penetrating keratoplasty in 2013. Secondary endothelial failure is the top indication for performing a keratoplasty over the 12-year period. There was a shift from penetrating keratoplasty to endothelial keratoplasty performed for Fuchs endothelial corneal dystrophy and secondary endothelial failure, and to deep anterior lamellar keratoplasty, performed for keratoconus. This highlights an important shift in managing corneal diseases toward the application of selective and more conservative surgeries and changes in indications in corneal transplantation.

Expression of heat shock protein in the atrophic corneal epithelium of the Royal College of Surgeons dystrophic rat.

PubMed

Yamaguchi, K; Yamaguchi, K; Sheedlo, H J; Turner, J E

1991-03-01

We report atrophic changes in the corneal epithelium of Royal College of Surgeons (RCS) dystrophic rats. The thickness of the corneal epithelium of 180-day-old RCS dystrophic rats was significantly decreased compared to that of 26-day-old RCS dystrophic and age-matched Sprague-Dawley (SD) rats. Immunostaining for (Na+ + K+) ATPase in the corneal epithelium of 180-day-old RCS dystrophic rats was dramatically reduced when compared to that of 26-day-old RCS dystrophic and age-matched SD rats. In contrast, heat shock protein immunostaining in the corneal epithelium was dense in all of the basal cells, wing cells, and superficial cells of 180-day-old RCS dystrophic rats but was minimally observed in some of the basal cells and in fewer wing and superficial cells of the corneal epithelium of 26-day-old RCS dystrophic and age-matched SD rats. We speculate that toxic products from the degenerating rod outer segments in the course of retinal dystrophy may affect the corneal epithelium, resulting in its atrophy. It is also possible that heat shock proteins appear in the atrophic corneal epithelium due to its degenerative condition.

Thermosensitive chitosan-based hydrogels for sustained release of ferulic acid on corneal wound healing.

PubMed

Tsai, Ching-Yao; Woung, Lin-Chung; Yen, Jiin-Cherng; Tseng, Po-Chen; Chiou, Shih-Hwa; Sung, Yen-Jen; Liu, Kuan-Ting; Cheng, Yung-Hsin

2016-01-01

Oxidative damage to cornea can be induced by alkaline chemical burn which may cause vision loss or blindness. Recent studies showed that exogenous application of natural antioxidants may be a potential treatment for corneal wound healing. However, low ocular bioavailability and short residence time are the limiting factors of topically administered antioxidants. Ferulic acid (FA) is a natural phenolic compound and an excellent antioxidant. The study was aimed to investigate the effects of FA in corneal epithelial cells (CECs) under oxidative stress and evaluate the feasibility of use the thermosensitive chitosan-based hydrogel containing FA for corneal wound healing. The results demonstrated that post-treatment of FA on CECs could decrease the inflammation-level and apoptosis. In the rabbit corneal alkali burn model, post-treatment FA-loaded hydrogel may promote the corneal wound healing. The results of study suggest that FA-loaded hydrogel may have the potential applications in treating corneal alkali burn. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Current approaches to evaluating the anatomic and functional status of the cornea].

PubMed

Avetisov, S E; Borodina, N V; Kobzova, M V; Musaeva, G M

2010-01-01

The review provides data on current methods for evaluating the anatomic and functional status of the cornea (light refraction, light transmission, and biomechanical properties, in particular). It analyzes the main advantages and disadvantages of basic (biomicroscopy, endothelial microscopy, ophthalmometry, topography, and pachymetry) and special (confocal microscopy, optical coherence tomography, ultrasound biomicroscopy, aberrometry, bidirectional corneal applanation, and keratoesthesiometry) studies.

Clinical Outcomes of an Optimized Prolate Ablation Procedure for Correcting Residual Refractive Errors Following Laser Surgery.

PubMed

Chung, Byunghoon; Lee, Hun; Choi, Bong Joon; Seo, Kyung Ryul; Kim, Eung Kwon; Kim, Dae Yune; Kim, Tae-Im

2017-02-01

The purpose of this study was to investigate the clinical efficacy of an optimized prolate ablation procedure for correcting residual refractive errors following laser surgery. We analyzed 24 eyes of 15 patients who underwent an optimized prolate ablation procedure for the correction of residual refractive errors following laser in situ keratomileusis, laser-assisted subepithelial keratectomy, or photorefractive keratectomy surgeries. Preoperative ophthalmic examinations were performed, and uncorrected distance visual acuity, corrected distance visual acuity, manifest refraction values (sphere, cylinder, and spherical equivalent), point spread function, modulation transfer function, corneal asphericity (Q value), ocular aberrations, and corneal haze measurements were obtained postoperatively at 1, 3, and 6 months. Uncorrected distance visual acuity improved and refractive errors decreased significantly at 1, 3, and 6 months postoperatively. Total coma aberration increased at 3 and 6 months postoperatively, while changes in all other aberrations were not statistically significant. Similarly, no significant changes in point spread function were detected, but modulation transfer function increased significantly at the postoperative time points measured. The optimized prolate ablation procedure was effective in terms of improving visual acuity and objective visual performance for the correction of persistent refractive errors following laser surgery.

Caveolins and caveolae in ocular physiology and pathophysiology.

PubMed

Gu, Xiaowu; Reagan, Alaina M; McClellan, Mark E; Elliott, Michael H

2017-01-01

Caveolae are specialized, invaginated plasma membrane domains that are defined morphologically and by the expression of signature proteins called, caveolins. Caveolae and caveolins are abundant in a variety of cell types including vascular endothelium, glia, and fibroblasts where they play critical roles in transcellular transport, endocytosis, mechanotransduction, cell proliferation, membrane lipid homeostasis, and signal transduction. Given these critical cellular functions, it is surprising that ablation of the caveolae organelle does not result in lethality suggesting instead that caveolae and caveolins play modulatory roles in cellular homeostasis. Caveolar components are also expressed in ocular cell types including retinal vascular cells, Müller glia, retinal pigment epithelium (RPE), conventional aqueous humor outflow cells, the corneal epithelium and endothelium, and the lens epithelium. In the eye, studies of caveolae and other membrane microdomains (i.e., "lipid rafts") have lagged behind what is a substantial body of literature outside vision science. However, interest in caveolae and their molecular components has increased with accumulating evidence of important roles in vision-related functions such as blood-retinal barrier homeostasis, ocular inflammatory signaling, pathogen entry at the ocular surface, and aqueous humor drainage. The recent association of CAV1/2 gene loci with primary open angle glaucoma and intraocular pressure has further enhanced the need to better understand caveolar functions in the context of ocular physiology and disease. Herein, we provide the first comprehensive review of literature on caveolae, caveolins, and other membrane domains in the context of visual system function. This review highlights the importance of caveolae domains and their components in ocular physiology and pathophysiology and emphasizes the need to better understand these important modulators of cellular function. Copyright © 2016 Elsevier Ltd. All rights reserved.

Caveolins and caveolae in ocular physiology and pathophysiology

PubMed Central

Gu, Xiaowu; Reagan, Alaina M.; McClellan, Mark E.; Elliott, Michael H.

2016-01-01

Caveolae are specialized, invaginated plasma membrane domains that are defined morphologically and by the expression of signature proteins called, caveolins. Caveolae and caveolins are abundant in a variety of cell types including vascular endothelium, glia, and fibroblasts where they play critical roles in transcellular transport, endocytosis, mechanotransduction, cell proliferation, membrane lipid homeostasis, and signal transduction. Given these critical cellular functions, it is surprising that ablation of the caveolae organelle does not result in lethality suggesting instead that caveolae and caveolins play modulatory roles in cellular homeostasis. Caveolar components are also expressed in ocular cell types including retinal vascular cells, Müller glia, retinal pigment epithelium (RPE), conventional aqueous humor outflow cells, the corneal epithelium and endothelium, and the lens epithelium. In the eye, studies of caveolae and other membrane microdomains (i.e., “lipid rafts”) have lagged behind what is a substantial body of literature outside vision science. However, interest in caveolae and their molecular components has increased with accumulating evidence of important roles in vision-related functions such as blood-retinal barrier homeostasis, ocular inflammatory signalling, pathogen entry at the ocular surface, and aqueous humor drainage. The recent association of CAV1/2 gene loci with primary open angle glaucoma and intraocular pressure has further enhanced the need to better understand caveolar functions in the context of ocular physiology and disease. Herein, we provide the first comprehensive review of literature on caveolae, caveolins, and other membrane domains in the context of visual system function. This review highlights the importance of caveolae domains and their components in ocular physiology and pathophysiology and emphasizes the need to better understand these important modulators of cellular function. PMID:27664379

Management of chemical burns of the canine cornea

PubMed Central

Christmas, Richard

1991-01-01

Significant clinical signs and general principles of treatment for chemical burns of the canine cornea are presented using three typical case studies for illustration. Alkali burns are more common in dogs than acid burns. The sources of alkali in this study were soap, cement, and mortar dust. Common signs of chemical burns are ocular pain, corneal ulceration, tear film inadequacy, corneal edema, and marked corneal neovascularity. Successful treatment requires thorough ocular lavage, treatment for corneal ulceration, and adequate anti-inflammatory therapy when the corneal epithelium becomes intact. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5. PMID:17423874