Corneal arcus: an indicator of severe coronary artery disease in a young adult man.

PubMed

Sucu, Murat; Davutoglu, Vedat

2009-01-01

A 32-year-old man was transferred to our emergency service with the diagnosis of sudden cardiopulmonary arrest. During eye examination, a typical corneal arcus was observed. The patient underwent the primary percutaneous coronary intervention. Coronary angiography showed a total occlusion of proximal left anterior descending artery. Primary coronary balloon angioplasty was successfully performed. Independently of total cholesterol, serum high-density lipoprotein cholesterol and smoking, corneal arcus has been suggested as a predictor of coronary heart disease among hyperlipidemic men. Physical examination can yield valuable diagnostic clues in a patient suspected of ischaemic heart disease. In summary, the appearance of corneal arcus in young adult men might be an indicator of severe coronary artery disease and should be screened by means of physical examination especially in the setting of cardiopulmonary arrest (Fig. 1, Ref. 4).

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

Human Adenovirus Type 37 Uses αVβ1 and α3β1 Integrins for Infection of Human Corneal Cells

PubMed Central

Storm, Rickard J.; Persson, B. David; Skalman, Lars Nygård; Frängsmyr, Lars; Lindström, Mona; Rankin, Greg; Lundmark, Richard; Domellöf, Fatima Pedrosa

2016-01-01

ABSTRACT Epidemic keratoconjunctivitis (EKC) is a severe, contagious ocular disease that affects 20 to 40 million individuals worldwide every year. EKC is mainly caused by six types of human adenovirus (HAdV): HAdV-8, -19, -37, -53, -54, and -56. Of these, HAdV-8, -19, and -37 use sialic acid-containing glycans as cellular receptors. αVβ3, αVβ5, and a few additional integrins facilitate entry and endosomal release of other HAdVs. With the exception of a few biochemical analyses indicating that HAdV-37 can interact physically with αVβ5, little is known about the integrins used by EKC-causing HAdVs. Here, we investigated the overall integrin expression on human corneal cells and found expression of α2, α3, α6, αV, β1, and β4 subunits in human corneal in situ epithelium and/or in a human corneal epithelial (HCE) cell line but no or less accessible expression of α4, α5, β3, or β5. We also identified the integrins used by HAdV-37 through a series of binding and infection competition experiments and different biochemical approaches. Together, our data suggest that HAdV-37 uses αVβ1 and α3β1 integrins for infection of human corneal epithelial cells. Furthermore, to confirm the relevance of these integrins in the HAdV-37 life cycle, we developed a corneal multilayer tissue system and found that HAdV-37 infection correlated well with the patterns of αV, α3, and β1 integrin expression. These results provide further insight into the tropism and pathogenesis of EKC-causing HAdVs and may be of importance for future development of new antiviral drugs. IMPORTANCE Keratitis is a hallmark of EKC, which is caused by six HAdV types (HAdV-8, -19, -37, -53, -54, and -56). HAdV-37 and some other HAdV types interact with integrin αVβ5 in order to enter nonocular human cells. In this study, we found that αVβ5 is not expressed on human corneal epithelial cells, thus proposing other host factors mediate corneal infection. Here, we first characterized integrin

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.

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

Interference figures of polarimetric interferometry analysis of the human corneal stroma

PubMed Central

Mastropasqua, Rodolfo; Nubile, Mario; Salgari, Niccolò; Lanzini, Manuela; Calienno, Roberta; Mattei, Peter A.; Sborgia, Alessandra; Agnifili, Luca

2017-01-01

A rotating polarimetric 90°-cross linear-filter interferometry system was used to detect the morphological characteristics and features of interference patterns produced in in-vivo corneal stroma in healthy human corneas of 23 subjects. The characteristic corneal isogyres presenting with an evident cross-shaped pattern, grossly aligned with the fixation axis, were observed in all patients with centers within the pupillary dark area, impeding the exact determination of the center point. During the rotational scan in 78.3% of the eyes the cross-shaped pattern of the isogyre gradually separated to form two distinct hyperbolic arcs in opposite quadrants, reaching their maximal separation at 45 degrees with respect to angle of cross-shaped pattern formation. The corneal cross and hyperbolic-pattern repeated every 90° throughout the 360° rotational scan. While the interpretation of the isogyres presents particular difficulties, two summary parameters can be extracted for each cornea: the presence/orientation of a single or two dark areas in post-processed images and isochromes. However, the development of dedicated software for semi-quantitative analysis of these parameters and enantiomorphism may become available in the near future. The possible application of polarimetric interferometry in the field of both corneal pathologies and corneal surgery may be of great interest for clinical purposes. PMID:28570631

Interference figures of polarimetric interferometry analysis of the human corneal stroma.

PubMed

Mastropasqua, Rodolfo; Nubile, Mario; Salgari, Niccolò; Lanzini, Manuela; Calienno, Roberta; Mattei, Peter A; Sborgia, Alessandra; Agnifili, Luca

2017-01-01

A rotating polarimetric 90°-cross linear-filter interferometry system was used to detect the morphological characteristics and features of interference patterns produced in in-vivo corneal stroma in healthy human corneas of 23 subjects. The characteristic corneal isogyres presenting with an evident cross-shaped pattern, grossly aligned with the fixation axis, were observed in all patients with centers within the pupillary dark area, impeding the exact determination of the center point. During the rotational scan in 78.3% of the eyes the cross-shaped pattern of the isogyre gradually separated to form two distinct hyperbolic arcs in opposite quadrants, reaching their maximal separation at 45 degrees with respect to angle of cross-shaped pattern formation. The corneal cross and hyperbolic-pattern repeated every 90° throughout the 360° rotational scan. While the interpretation of the isogyres presents particular difficulties, two summary parameters can be extracted for each cornea: the presence/orientation of a single or two dark areas in post-processed images and isochromes. However, the development of dedicated software for semi-quantitative analysis of these parameters and enantiomorphism may become available in the near future. The possible application of polarimetric interferometry in the field of both corneal pathologies and corneal surgery may be of great interest for clinical purposes.

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.

Rho GTPases and Regulation of Cell Migration and Polarization in Human Corneal Epithelial Cells

PubMed Central

Hou, Aihua; Toh, Li Xian; Gan, Kah Hui; Lee, Khee Jin Ryan; Manser, Edward; Tong, Louis

2013-01-01

Purpose Epithelial cell migration is required for regeneration of tissues and can be defective in a number of ocular surface diseases. This study aimed to determine the expression pattern of Rho family small G-proteins in human corneal epithelial cells to test their requirement in directional cell migration. Methods Rho family small G-protein expression was assessed by reverse transcription-polymerase chain reaction. Dominant-inhibitory constructs encoding Rho proteins or Rho protein targeting small interfering RNA were transfected into human corneal epithelial large T antigen cells, and wound closure rate were evaluated by scratch wounding assay, and a complementary non-traumatic cell migration assay. Immunofluorescence staining was performed to study cell polarization and to assess Cdc42 downstream effector. Results Cdc42, Chp, Rac1, RhoA, TC10 and TCL were expressed in human corneal epithelial cells. Among them, Cdc42 and TCL were found to significantly affect cell migration in monolayer scratch assays. These results were confirmed through the use of validated siRNAs directed to Cdc42 and TCL. Scramble siRNA transfected cells had high percentage of polarized cells than Cdc42 or TCL siRNA transfected cells at the wound edge. We showed that the Cdc42-specific effector p21-activated kinase 4 localized predominantly to cell-cell junctions in cell monolayers, but failed to translocate to the leading edge in Cdc42 siRNA transfected cells after monolayer wounding. Conclusion Rho proteins expressed in cultured human corneal epithelial cells, and Cdc42, TCL facilitate two-dimensional cell migration in-vitro. Although silencing of Cdc42 and TCL did not noticeably affect the appearance of cell adhesions at the leading edge, the slower migration of these cells indicates both GTP-binding proteins play important roles in promoting cell movement of human corneal epithelial cells. PMID:24130842

[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

Propagation of human corneal endothelial cells: a novel dual media approach.

PubMed

Peh, Gary S L; Chng, Zhenzhi; Ang, Heng-Pei; Cheng, Terence Y D; Adnan, Khadijah; Seah, Xin-Yi; George, Benjamin L; Toh, Kah-Peng; Tan, Donald T; Yam, Gary H F; Colman, Alan; Mehta, Jodhbir S

2015-01-01

Corneal endothelium-associated corneal blindness is the most common indication for corneal transplantation. Restorative corneal transplant surgery is the only option to reverse the blindness, but a global shortage of donor material remains an issue. There are immense clinical interests in the development of alternative treatment strategies to alleviate current reliance on donor materials. For such endeavors, ex vivo propagation of human corneal endothelial cells (hCECs) is required, but current methodology lacks consistency, with expanded hCECs losing cellular morphology to a mesenchymal-like transformation. In this study, we describe a novel dual media culture approach for the in vitro expansion of primary hCECs. Initial characterization included analysis of growth dynamics of hCECs grown in either proliferative (M4) or maintenance (M5) medium. Subsequent comparisons were performed on isolated hCECs cultured in M4 alone against cells expanded using the dual media approach. Further characterizations were performed using immunocytochemistry, quantitative real-time PCR, and gene expression microarray. At the third passage, results showed that hCECs propagated using the dual media approach were homogeneous in appearance, retained their unique polygonal cellular morphology, and expressed higher levels of corneal endothelium-associated markers in comparison to hCECs cultured in M4 alone, which were heterogeneous and fibroblastic in appearance. Finally, for hCECs cultured using the dual media approach, global gene expression and pathway analysis between confluent hCECs before and after 7-day exposure to M5 exhibited differential gene expression associated predominately with cell proliferation and wound healing. These findings showed that the propagation of primary hCECs using the novel dual media approach presented in this study is a consistent method to obtain bona fide hCECs. This, in turn, will elicit greater confidence in facilitating downstream development of

Modulating endogenous electric currents in human corneal wounds--a novel approach of bioelectric stimulation without electrodes.

PubMed

Reid, Brian; Graue-Hernandez, Enrique O; Mannis, Mark J; Zhao, Min

2011-03-01

To measure electric current in human corneal wounds and test the feasibility of pharmacologically enhancing the current to promote corneal wound healing. Using a noninvasive vibrating probe, corneal electric current was measured before and after wounding of the epithelium of donated postmortem human corneas. The effects of drug aminophylline and chloride-free solution on wound current were also tested. Unwounded cornea had small outward currents (0.07 μA/cm²). Wounding increased the current more than 5 fold (0.41 μA/cm²). Monitoring the wound current over time showed that it seemed to be actively regulated and maintained above normal unwounded levels for at least 6 hours. The time course was similar to that previously measured in rat cornea. Drug treatment or chloride-free solution more than doubled the size of wound currents. Electric current at human corneal wounds can be significantly increased with aminophylline or chloride-free solution. Because corneal wound current directly correlates with wound healing rate, our results suggest a role for chloride-free and/or aminophylline eyedrops to enhance healing of damaged cornea in patients with reduced wound healing such as the elderly or diabetic patient. This novel approach offers bioelectric stimulation without electrodes and can be readily tested in patients.

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.

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.

Effect of corneal wetting solutions on corneal thickness during ophthalmic surgery.

PubMed

Emre, Sinan; Akkin, Cezmi; Afrashi, Filiz; Yağci, Ayşe

2002-01-01

To measure the changes in corneal thickness with wetting solutions used in ophthalmic surgery. Ege University, School of Medicine, Department of Ophthalmology, Izmir, Turkey. Thirty-one adult pigmented rabbits that weighed about 2.5 kg each were anesthetized with pentobarbital sodium. The rabbits were randomly divided into 3 groups to receive 3 wetting solutions: Group 1, Ringer's lactate; Group 2, balanced salt solution (BSS); and Group 3, BSS with glutation (BSS Plus). The solutions were dropped on the right cornea of the rabbits at a rate of 6.0 cc in 12 minutes using an intravenous infusion pump. Corneal thickness was measured by ultrasonic pachymetry before and after the procedure, and the between-group changes in corneal thickness were compared. The corneal thickness before and after the procedure was 361.27 microm +/- 19.3 (SD) and 380.00 +/- 25.0 microm, respectively, in Group 1 (P =.000); 372.10 +/- 18.8 microm and 388.60 +/- 24.1 microm, respectively, in Group 2 (P =.003); and 358.10 +/- 26.5 microm and 360.10 +/- 24.1 microm, respectively, in Group 3 (P =.316). As a corneal wetting solution, BSS Plus resulted in significantly fewer changes in corneal thickness than Ringer's lactate or BSS. This should be considered in cases involving long intraocular surgery.

New Details of the Human Corneal Limbus Revealed With Second Harmonic Generation Imaging.

PubMed

Park, Choul Yong; Lee, Jimmy K; Zhang, Cheng; Chuck, Roy S

2015-09-01

To report novel findings of the human corneal limbus by using second harmonic generation (SHG) imaging. Corneal limbus was imaged by using an inverted two-photon excitation fluorescence microscope. Laser (Ti:Sapphire) was tuned at 850 nm for two-photon excitation. Backscatter signals of SHG and autofluorescence (AF) were collected through a 425/30-nm emission filter and a 525/45-emission filter, respectively. Multiple, consecutive, and overlapping image stacks (z-stack) were acquired for the corneal limbal area. Two novel collagen structures were revealed by SHG imaging at the limbus: an anterior limbal cribriform layer and presumed anchoring fibers. Anterior limbal cribriform layer is an intertwined reticular collagen architecture just beneath the limbal epithelial niche and is located between the peripheral cornea and Tenon's/scleral tissue. Autofluorescence imaging revealed high vascularity in this structure. Central to the anterior limbal cribriform layer, radial strands of collagen were found to connect the peripheral cornea to the limbus. These presumed anchoring fibers have both collagen and elastin and were found more extensively in the superficial layers than deep layer and were absent in very deep limbus near Schlemm's canal. By using SHG imaging, new details of the collagen architecture of human corneal limbal area were elucidated. High resolution images with volumetric analysis revealed two novel collagen structures.

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.

Assessment of the reliability of human corneal endothelial cell-density estimates using a noncontact specular microscope.

PubMed

Doughty, M J; Müller, A; Zaman, M L

2000-03-01

We sought to determine the variance in endothelial cell density (ECD) estimates for human corneal endothelia. Noncontact specular micrographs were obtained from white subjects without any history of contact lens wear, or major eye disease or surgery; subjects were within four age groups (children, young adults, older adults, senior citizens). The endothelial image was scanned, and the areas from > or =75 cells measured from an overlay by planimetry. The cell-area values were used to calculate the ECD repeatedly so that the intra- and intersubject variation in an average ECD estimate could be made by using different numbers of cells (5, 10, 15, etc.). An average ECD of 3,519 cells/mm2 (range, 2,598-5,312 cells/mm2) was obtained of counts of 75 cells/ endothelium from individuals aged 6-83 years. Average ECD estimates in each age group were 4,124, 3,457, 3,360, and 3,113 cells/mm2, respectively. Analysis of intersubject variance revealed that ECD estimates would be expected to be no better than +/-10% if only 25 cells were measured per endothelium, but approach +/-2% if 75 cells are measured. In assessing the corneal endothelium by noncontact specular microscopy, cell count should be given, and this should be > or =75/ endothelium for an expected variance to be at a level close to that recommended for monitoring age-, stress-, or surgery-related changes.

Identification of cytomegalovirus and human herpesvirus-6 DNA in a patient with corneal endotheliitis.

PubMed

Yokogawa, Hideaki; Kobayashi, Akira; Yamazaki, Natsuko; Sugiyama, Kazuhisa

2013-03-01

To report the case of a patient with unilateral corneal endotheliitis in which both cytomegalovirus (CMV) and human herpesvirus-6 (HHV6) DNA was identified in the aqueous humor. A 67-year-old man with corneal endotheliitis OD was referred to us for decreased visual acuity. Local corneal stromal edema, pigmented keratic precipitates, a coin-shaped lesion and minimal anterior chamber reaction were observed by slit-lamp biomicroscopy. Cells with owl's eye appearance in the endothelial cell layer were observed by in vivo laser confocal microscopy. The patient had rheumatoid arthritis, which was treated by oral prednisolone and intravenous abatacept. Polymerase chain reaction analysis of aqueous humor samples detected both CMV and HHV6 DNA, but not other HHVs. Treatment with topical ganciclovir and systemic valganciclovir resulted in a clear cornea. A patient with corneal endotheliitis had both CMV and HHV6 DNA identified in the aqueous humor. Although both viruses were identified in this case, clinical manifestations resembled CMV corneal endotheliitis, and it was unclear whether HHV6 could affect the clinical course. Systemic abatacept and corticosteroid therapy might play a positive role in cases with both CMV and HHV6 DNA in this corneal endotheliitis.

Corneal Ring Infiltrates Caused by Serratia marcescens in a Patient with Human Immunodeficiency Virus.

PubMed

Chaidaroon, Winai; Supalaset, Sumet

2016-01-01

To describe corneal ring infiltrates caused by Serratia marcescens in a patient with human immunodeficiency virus (HIV-1) who wore contact lenses. A case study of a patient with keratitis due to an infection caused by S. marcescens and exhibiting corneal ring infiltrates was reviewed for history, clinical manifestation, microscopic study, and management. A 29-year-old man who had a history of contact lens wear and HIV-1 infection was admitted to hospital because of blurred vision, redness, and corneal infiltrates in the shape of a ring in the left eye. The visual acuity (VA) in both eyes was hand movement (uncorrected). Corneal scrapings were performed. The culture results of the corneal specimens revealed S. marcescens . The culture results of the contact lens disclosed the same organism. The corneal ulcer responded well to treatment with topical gentamycin sulfate 14 mg/ml. The final VA remained hand movement. S. marcescens can cause ring infiltrates in a HIV-1 patient who wears contact lenses. The treatment result for S. marcescens keratitis in a HIV-1 patient who wore contact lenses was favorable after intensive use of fortified topical antibiotics.

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.

Regulation of membrane-associated mucins in the human corneal epithelial cells by dexamethasone.

PubMed

Seo, Kyoung Yul; Chung, So-Hyang; Lee, Joon H; Park, Mi Young; Kim, Eung Kweon

2007-07-01

To study the influence of dexamethasone on membrane-associated mucins produced by human corneal epithelial cells. Human corneal epithelial cells were cultured in medium supplemented with various concentrations of dexamethasone (ranging from 10 to 10 M). Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis using monoclonal antibodies specific for human MUC1 (HMFG-1), MUC4 (1G8), and MUC16 (OC125) were performed to evaluate the effect of dexamethasone on membrane-associated mucin expression. The effect of glucocorticoid receptor antagonist (RU38486) on dexamethasone-induced mucin expression was estimated. RT-PCR revealed that MUC1 and MUC16 gene expression were upregulated 48 hours after addition of dexamethasone and that MUC4 gene expression was downregulated in the same condition. Western blot analysis showed that MUC1 and MUC16 proteins were increased after addition of dexamethasone. However, MUC4 was not detected by anti-MUC4 monoclonal antibody (1G8) for ASGP-2 under our conditions. Treatment with RU38486 inhibited the changes of MUC1, MUC4, and MUC16 by dexamethasone; thus, the effect of dexamethasone on mucin expression is mediated by glucocorticoid receptors. This study shows that MUC1, MUC4, and MUC16 are regulated differently by dexamethasone in human corneal epithelial cells. External application of dexamethasone might affect the precorneal mucin.

Human induced pluripotent stem cell differentiation and direct transdifferentiation into corneal epithelial-like cells

PubMed Central

Cieślar-Pobuda, Artur; Rafat, Mehrdad; Knoflach, Viktoria; Skonieczna, Magdalena; Hudecki, Andrzej; Małecki, Andrzej; Urasińska, Elżbieta; Ghavami, Seaid; Łos, Marek J.

2016-01-01

The corneal epithelium is maintained by a small pool of tissue stem cells located at the limbus. Through certain injuries or diseases this pool of stem cells may get depleted. This leads to visual impairment. Standard treatment options include autologous or allogeneic limbal stem cell (LSC) transplantation, however graft rejection and chronic inflammation lowers the success rate over long time. Induced pluripotent stem (iPS) cells have opened new possibilities for treating various diseases with patient specific cells, eliminating the risk of immune rejection. In recent years, several protocols have been developed, aimed at the differentiation of iPS cells into the corneal epithelial lineage by mimicking the environmental niche of limbal stem cells. However, the risk of teratoma formation associated with the use of iPS cells hinders most applications from lab into clinics. Here we show that the differentiation of iPS cells into corneal epithelial cells results in the expression of corneal epithelial markers showing a successful differentiation, but the process is long and the level of gene expression for the pluripotency markers does not vanish completely. Therefore we set out to determine a direct transdifferentiation approach to circumvent the intermediate state of pluripotency (iPS-stage). The resulting cells, obtained by direct transdifferentiation of fibroblasts into limbal cells, exhibited corneal epithelial cell morphology and expressed corneal epithelial markers. Hence we shows for the first time a direct transdifferentiation of human dermal fibroblasts into the corneal epithelial lineage that may serve as source for corneal epithelial cells for transplantation approaches. PMID:27275539

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

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.

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.

Oxidative stress gradient in a medium during human corneal organ culture

PubMed Central

Johnsen-Soriano, Siv; Haug, Kristiane; Arnal, Emma; Peris-Martinez, Cristina; Moe, Morten C.

2012-01-01

Purpose Lipid peroxidation content was measured in an organ culture medium after one-week storage of human donor corneas. Moreover, the effects of the medium on oxidative stress, antioxidant capacity, and the proliferation of cultured human corneal cells were studied. Methods The medium was sampled from the upper and lower halves of storage vials and from controls (n=42). Malondialdehyde (MDA) was measured by high pressure liquid chromatography (HPLC). Cultured human corneal epithelium (CRL-11515) was exposed to different medium samples and monitored for changes in MDA (enzyme-linked immunosorbent assay [ELISA]), total antioxidant capacity (antioxidant assay kit), and proliferation (Ki-67). Results A significant increase in MDA was observed in the organ culture medium in the lower level of storage vials. The addition of this fraction to cultured cells increased MDA significantly after 3 days, and the medium from both levels significantly increased MDA after 7 days. The medium from both levels significantly decreased the total antioxidant capacity of the cells but did not affect proliferative activity. Conclusions An oxidative gradient with an evident biologic effect is established in the medium in vials during organ culture of human donor corneas. Donor tissue stored at the bottom or in lower levels of such vials is exposed to a significant amount of oxidative stress. PMID:22736949

[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

Alarmins from corneal epithelial cells upregulate CCL11 and VCAM-1 in corneal fibroblasts.

PubMed

Fukuda, Ken; Ishida, Waka; Tanaka, Hiroshi; Harada, Yosuke; Matsuda, Akira; Ebihara, Nobuyuki; Fukushima, Atsuki

2013-08-27

Severe ocular allergic diseases are characterized by pronounced conjunctival inflammation triggered by T helper 2 (Th2) cells and corneal epithelial damage induced by eosinophils. To examine the role of alarmins released by damaged corneal epithelial cells in tissue eosinophilia, we investigated the effects of a supernatant derived from necrotic human corneal epithelial (HCE) cells on expression of the chemokine CCL11 (eotaxin) and the adhesion molecule VCAM-1 in human corneal fibroblasts. An alarmin preparation was obtained as the material released from HCE cells after three cycles of freezing and thawing. CCL11 released into culture medium and cell surface expression of VCAM-1 were measured with enzyme-linked immunosorbent assays, and the amounts of CCL11 and VCAM-1 mRNAs were quantitated by reverse transcription and real-time polymerase chain reaction analysis. Signaling by the transcription factor NF-κB was evaluated by immunoblot and immunofluorescence analyses. The combination of the necrotic HCE cell supernatant and either interleukin (IL)-4 or IL-13 induced synergistic increases in CCL11 release, VCAM-1 expression, and the abundance of CCL11 and VCAM-1 mRNAs in corneal fibroblasts. The necrotic HCE cell supernatant also induced NF-κB activation in corneal fibroblasts, whereas an inhibitor of NF-κB and IL-1 receptor antagonist each attenuated CCL11 release induced by the alarmin preparation and either IL-4 or IL-13. Alarmins including IL-1 released from necrotic corneal epithelial cells cooperate with Th2 cytokines to induce CCL11 production and VCAM-1 expression in corneal fibroblasts, and may thereby play an important role in tissue eosinophilia associated with ocular allergic diseases.

In vivo three-dimensional imaging of human corneal nerves using Fourier-domain optical coherence tomography

NASA Astrophysics Data System (ADS)

Shin, Jun Geun; Hwang, Ho Sik; Eom, Tae Joong; Lee, Byeong Ha

2017-01-01

We have employed Fourier-domain optical coherence tomography (FD-OCT) to achieve corneal nerve imaging, which could be useful in surgical planning and refractive surgery. Because the three-dimensional (3-D) images of the corneal nerves were acquired in vivo, unintentional movement of the subject during the measurement led to imaging artifacts. These artifacts were compensated for with a series of signal processing techniques, namely realigning A-scan images to flatten the boundary and cross-correlating adjacent B-scan images. To overcome the undesirably large signal from scattering at the corneal surface and iris, volume rendering and maximum intensity projections were performed with only the data taken in the stromal region of the cornea, which is located between 200 and 500 μm from the corneal surface. The 3-D volume imaging of a 10×10 mm2 area took 9.8 s, which is slightly shorter than the normal tear breakup time. This allowed us to image the branched and threadlike corneal nerve bundles within the human eye. The experimental results show that FD-OCT systems have the potential to be useful in clinical investigations of corneal nerves and by minimizing nerve injury during clinical or surgical procedures.

The tissue-engineered human cornea as a model to study expression of matrix metalloproteinases during corneal wound healing.

PubMed

Couture, Camille; Zaniolo, Karine; Carrier, Patrick; Lake, Jennifer; Patenaude, Julien; Germain, Lucie; Guérin, Sylvain L

2016-02-01

Corneal injuries remain a major cause of consultation in the ophthalmology clinics worldwide. Repair of corneal wounds is a complex mechanism that involves cell death, migration, proliferation, differentiation, and extracellular matrix (ECM) remodeling. In the present study, we used a tissue-engineered, two-layers (epithelium and stroma) human cornea as a biomaterial to study both the cellular and molecular mechanisms of wound healing. Gene profiling on microarrays revealed important alterations in the pattern of genes expressed by tissue-engineered corneas in response to wound healing. Expression of many MMPs-encoding genes was shown by microarray and qPCR analyses to increase in the migrating epithelium of wounded corneas. Many of these enzymes were converted into their enzymatically active form as wound closure proceeded. In addition, expression of MMPs by human corneal epithelial cells (HCECs) was affected both by the stromal fibroblasts and the collagen-enriched ECM they produce. Most of all, results from mass spectrometry analyses provided evidence that a fully stratified epithelium is required for proper synthesis and organization of the ECM on which the epithelial cells adhere. In conclusion, and because of the many characteristics it shares with the native cornea, this human two layers corneal substitute may prove particularly useful to decipher the mechanistic details of corneal wound healing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Optical and Biometric Characteristics of Anisomyopia in Human Adults

PubMed Central

Tian, Yibin; Tarrant, Janice; Wildsoet, Christine F.

2011-01-01

Purpose To investigate the role of higher order optical aberrations and thus retinal image degradation in the development of myopia, through the characterization of anisomyopia in human adults in terms of their optical and biometric characteristics. Methods The following data were collected from both eyes of fifteen young adult anisometropic myopes and sixteen isometropic myopes: subjective and objective refractive errors, corneal power and shape, monochromatic optical aberrations, anterior chamber depth, lens thickness, vitreous chamber depth, and best corrected visual acuity. Monochromatic aberrations were analyzed in terms of their higher order components, and further analyzed in terms of 31 optical quality metrics. Interocular differences for the two groups (anisomyopes vs. isomyopes) were compared and the relationship between measured ocular parameters and refractive errors also analyzed across all eyes. Results As expected, anisomyopes and isomyopes differed significantly in terms of interocular differences in vitreous chamber depth, axial length and refractive error. However, interocular differences in other optical properties showed no significant intergroup differences. Overall, higher myopia was associated with deeper anterior and vitreous chambers, higher astigmatism, more prolate corneas, and more positive spherical aberration. Other measured optical and biometric parameters were not significantly correlated with spherical refractive error, although some optical quality metrics and corneal astigmatism were significantly correlated with refractive astigmatism. Conclusions An optical cause for anisomyopia related to increased higher order aberrations is not supported by our data. Corneal shape changes and increased astigmatism in more myopic eyes may be a by-product of the increased anterior chamber growth in these eyes; likewise, the increased positive spherical aberration in more myopic eyes may be a product of myopic eye growth. PMID:21797915

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.

Mitochondrial DNA common deletion in the human eye: a relation with corneal aging.

PubMed

Gendron, Sébastien P; Mallet, Justin D; Bastien, Nathalie; Rochette, Patrick J

2012-01-01

The most frequent mitochondrial DNA (mtDNA) mutation is a 4977 bp deletion known as the common deletion (mtDNA(CD4977)). mtDNA(CD4977) is related to skin photo-aging and to chronological aging of cells with high-energy demands such as neurons and muscle cells. The human eye contains both sun-exposed (cornea, iris) and high-energy demand structures (retina). In this study, we employed a highly sensitive quantitative PCR technique to determine mtDNA(CD4977) occurrence in different structures of the human eye. We found that the cornea, the most anterior structure of the eye, contains the highest amount of mtDNA(CD4977) (2.6%, 0.25% and 0.06% for the cornea, iris and retina, respectively). Within the cornea, mtDNA(CD4977) is almost exclusively found in the stroma, the cellular layer conferring transparency and rigidity to the human cornea (8.59%, 0.13% and 0.05% in the stroma, endothelium and epithelium, respectively). Moreover, we show that mtDNA(CD4977) accumulates with age in the corneal stroma. Taken together, our results suggest that mtDNA(CD4977) is related to photo-aging rather than chronological aging in the human eye. Similar to the involvement of mtDNA(CD4977) in skin photo-aging phenotypes, we believe that the clinical manifestations of corneal aging, including clouding and stiffening, are associated with the accumulation of mtDNA(CD4977) in the corneal stroma. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Biological length scale topography enhances cell-substratum adhesion of human corneal epithelial cells

PubMed Central

Karuri, Nancy W.; Liliensiek, Sara; Teixeira, Ana I.; Abrams, George; Campbell, Sean; Nealey, Paul F.; Murphy, Christopher J.

2006-01-01

Summary The basement membrane possesses a rich 3-dimensional nanoscale topography that provides a physical stimulus, which may modulate cell-substratum adhesion. We have investigated the strength of cell-substratum adhesion on nanoscale topographic features of a similar scale to that of the native basement membrane. SV40 human corneal epithelial cells were challenged by well-defined fluid shear, and cell detachment was monitored. We created silicon substrata with uniform grooves and ridges having pitch dimensions of 400-4000 nm using X-ray lithography. F-actin labeling of cells that had been incubated for 24 hours revealed that the percentage of aligned and elongated cells on the patterned surfaces was the same regardless of pitch dimension. In contrast, at the highest fluid shear, a biphasic trend in cell adhesion was observed with cells being most adherent to the smaller features. The 400 nm pitch had the highest percentage of adherent cells at the end of the adhesion assay. The effect of substratum topography was lost for the largest features evaluated, the 4000 nm pitch. Qualitative and quantitative analyses of the cells during and after flow indicated that the aligned and elongated cells on the 400 nm pitch were more tightly adhered compared to aligned cells on the larger patterns. Selected experiments with primary cultured human corneal epithelial cells produced similar results to the SV40 human corneal epithelial cells. These findings have relevance to interpretation of cell-biomaterial interactions in tissue engineering and prosthetic design. PMID:15226393

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.

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.

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

Effects of organophosphorus flame retardant TDCPP on normal human corneal epithelial cells: Implications for human health.

PubMed

Xiang, Ping; Liu, Rong-Yan; Li, Chao; Gao, Peng; Cui, Xin-Yi; Ma, Lena Q

2017-11-01

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is one of the most detected organophosphorus flame retardants (OPFRs) in the environment, especially in indoor dust. Continuous daily exposure to TDCPP-containing dust may adversely impact human cornea. However, its detrimental effects on human corneal epithelium are largely unknown. In this study, we investigated the cell apoptosis in normal human corneal epithelial cells (HCECs) after TDCPP exposure and elucidated the underlying molecular mechanisms. Our data indicated a dose-dependent decrease of cell viability after TDCPP exposure with LC 50 at 202 μg/mL. A concentration-dependent apoptotic sign was observed in HCECs after exposing to ≥2 μg/mL TDCPP. Endoplasmic reticulum stress induction was evidenced by up-regulation of its biomarker genes (ATF-4, CHOP, BiP, and XBP1). Furthermore, alternation of Bcl-2/Bax expression, mitochondrial membrane potential loss, cellular ATP content decrease, and caspase-3 and -9 activity increase were observed after exposing to 2 or 20 μg/mL TDCPP. Taken together, the data implicated the involvement of endoplasmic reticulum stress in TDCPP-induced HCEC apoptosis, probably mediated by mitochondrial apoptotic pathway. Our findings showed TDCPP exposure induced toxicity to human cornea. Due to TDCPP's presence at high levels in indoor dust, further study is warranted to evaluate its health risk on human corneas. Published by Elsevier Ltd.

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.

Multiscale Investigation of the Depth-Dependent Mechanical Anisotropy of the Human Corneal Stroma

PubMed Central

Labate, Cristina; Lombardo, Marco; De Santo, Maria P.; Dias, Janice; Ziebarth, Noel M.; Lombardo, Giuseppe

2015-01-01

Purpose. To investigate the depth-dependent mechanical anisotropy of the human corneal stroma at the tissue (stroma) and molecular (collagen) level by using atomic force microscopy (AFM). Methods. Eleven human donor corneas were dissected at different stromal depths by using a microkeratome. Mechanical measurements were performed in 15% dextran on the surface of the exposed stroma of each sample by using a custom-built AFM in force spectroscopy mode using both microspherical (38-μm diameter) and nanoconical (10-nm radius of curvature) indenters at 2-μm/s and 15-μm/s indentation rates. Young's modulus was determined by fitting force curve data using the Hertz and Hertz-Sneddon models for a spherical and a conical indenter, respectively. The depth-dependent anisotropy of stromal elasticity was correlated with images of the corneal stroma acquired by two-photon microscopy. Results. The force curves were obtained at stromal depths ranging from 59 to 218 μm. At the tissue level, Young's modulus (ES) showed a steep decrease at approximately 140-μm stromal depth (from 0.8 MPa to 0.3 MPa; P = 0.03) and then was stable in the posterior stroma. At the molecular level, Young's modulus (EC) was significantly greater than at the tissue level; EC decreased nonlinearly with increasing stromal depth from 3.9 to 2.6 MPa (P = 0.04). The variation of microstructure through the thickness correlated highly with a nonconstant profile of the mechanical properties in the stroma. Conclusions. The corneal stroma exhibits unique anisotropic elastic behavior at the tissue and molecular levels. This knowledge may benefit modeling of corneal behavior and help in the development of biomimetic materials. PMID:26098472

Corneal epithelial wound healing and bactericidal effect of conditioned medium from human uterine cervical stem cells.

PubMed

Bermudez, Maria A; Sendon-Lago, Juan; Eiro, Noemi; Treviño, Mercedes; Gonzalez, Francisco; Yebra-Pimentel, Eva; Giraldez, Maria Jesus; Macia, Manuel; Lamelas, Maria Luz; Saa, Jorge; Vizoso, Francisco; Perez-Fernandez, Roman

2015-01-22

To evaluate the effect of conditioned medium from human uterine cervical stem cells (CM-hUCESCs) on corneal epithelial healing in a rat model of dry eye after alkaline corneal epithelial ulcer. We also tested the bactericidal effect of CM-hUCESCs. Dry eye was induced in rats by extraocular lacrimal gland excision, and corneal ulcers were produced using NaOH. Corneal histologic evaluation was made with hematoxylin-eosin (H&E) staining. Real-time PCR was used to evaluate mRNA expression levels of proinflammatory cytokines. We also studied the bactericidal effect of CM-hUCESCs in vitro and on infected corneal contact lenses (CLs) using Escherichia coli and Staphylococcus epidermidis bacteria. In addition, in order to investigate proteins from CM-hUCESCs that could mediate these effects, we carried out a human cytokine antibody array. After injury, dry eyes treated with CM-hUCESCs significantly improved epithelial regeneration and showed reduced corneal macrophage inflammatory protein-1 alpha (MIP-1α) and TNF-α mRNA expression as compared to untreated eyes and eyes treated with culture medium or sodium hyaluronate ophthalmic drops. In addition, we found in CM-hUCESCs high levels of proteins, such as tissue inhibitors of metalloproteinases 1 and 2, fibroblast growth factor 6 and 7, urokinase receptor, and hepatocyte growth factor, that could mediate these effects. In vitro, CM-hUCESCs showed a clear bactericidal effect on both E. coli and S. epidermidis and CLs infected with S. epidermidis. Analyses of CM-hUCESCs showed elevated levels of proteins that could be involved in the bactericidal effect, such as the chemokine (C-X-C motif) ligands 1, 6, 8, 10, and the chemokine (C-C motif) ligands 5 and 20. Treatment with CM-hUCESCs improved wound healing of alkali-injured corneas and showed a strong bactericidal effect on CLs. Patients using CLs and suffering from dry eye, allergies induced by commercial solutions, or small corneal injuries could benefit from this treatment

Monocarboxylate Transporters Mediate Fluorescein Uptake in Corneal Epithelial Cells.

PubMed

Sun, Yi-Chen; Liou, Hau-Min; Yeh, Po-Ting; Chen, Wei-Li; Hu, Fung-Rong

2017-07-01

To determine the presence of monocarboxylate transporter (MCT) in human and rabbit corneal epithelium and its role in transcellular fluorescein transportation in the cornea. The presence of MCTs in human and rabbit corneal epithelium was determined by RT-PCR and immunohistochemistry. Intracellular fluorescein uptake experiment was performed using cultured human corneal epithelial cells (HCECs). The involvement of MCT in fluorescein uptake was determined by addition of MCT inhibitors to HCECs and acute dry eye model on New Zealand albino rabbits by spectrophotometry, corneal impression cytology, and external eye photographs. MCT-1 and MCT-4 were identified in both human and rabbit corneal epithelia. A longer treatment period and a lower pH value in culture medium increased fluorescein uptake in HCECs. Fluorescein uptake in HCECs was decreased following addition of MCT inhibitors in a concentration-dependent manner. Impression cytology under fluorescent microscopy showed intracellular fluorescein staining in the rabbit cornea with acute dry eye treatment that was decreased following topical treatment of MCT inhibitors. Fluorescein ingress in corneal epithelial cells is mediated by the MCT family. Further study of MCT-mediated transport on HCECs may potentially benefit differential diagnosis and contribute better understandings of ocular surface disorders.

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

Corneal endothelial autocrine trophic factor VIP in a mechanism-based strategy to enhance human donor cornea preservation for transplantation.

PubMed

Koh, Shay-Whey Margaret

2012-02-01

Vasoactive intestinal peptide (VIP) and ciliary neurotrophic factor (CNTF) are identified as autocrines of human corneal endothelial (CE) cells working in concert to maintain the differentiated state and promote the survival of the corneal endothelium. From VIP gene knockdown study, endogenous VIP is shown to maintain the level of the differentiation marker, the adhesion molecule N-cadherin, CE cell size, shape, and retention, in situ in the human donor corneoscleral explants. Exogenous VIP protects the corneal endothelium against the killing effect of oxidative stress, in part by upholding ATP levels in CE cells dying of oxidative stress-induced injury, allowing them to die of an apoptotic death instead of an acute necrotic one. The switch from the acute necrosis to the programmed cell death (apoptosis) may have allowed the injured CE cell to be rescued by the VIP-upregulated pathways, including those of Bcl-2 and N-cadherin, and resulted in long-term CE cell survival. The endogenous VIP in CE cells is upregulated by CNTF, which is released by CE cells surviving the oxidative stress. The CNTF receptor (CNTFRα) is expressed in CE cells in human donor corneoscleral explant and gradually becomes lost during corneal storage. VIP treatment (10(-8) M, 37 °C, 30 min) prior to storage of freshly dissected human donor corneoscleral explants increases their CE cell CNTFRα level and responsiveness to CNTF in upregulating the gap junctional protein connexin-43 expression. VIP treatment of both fresh and preserved corneoscleral explants reduces CE damage in the corneoscleral explants and in the corneal buttons trephined from them. CE cell loss is a critical risk factor in corneal graft failure at any time in the life of the graft, which can be as late as 5-10 years after an initially successful transplant. A new procedure, Descemet's stripping automated endothelial keratoplasty (DSAEK), which is superior to the traditional full thickness transplantation in many aspects

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

Human corneal endothelial cell transplantation using nanocomposite gel sheet in bullous keratopathy.

PubMed

Parikumar, Periasamy; Haraguchi, Kazutoshi; Senthilkumar, Rajappa; Abraham, Samuel Jk

2018-01-01

Transplantation of in vitro expanded human corneal endothelial precursors (HCEP) cells using a nanocomposite (D25-NC) gel sheet as supporting material in bovine's cornea has been earlier reported. Herein we report the transplantation of HCEP cells derived from a cadaver donor cornea to three patients using the NC gel sheet. In three patients with bullous keratopathy, one after cataract surgery, one after trauma and another in the corneal graft, earlier performed for congenital corneal dystrophy, not amenable to medical management HCEP cells isolated from a human cadaver donor cornea in vitro expanded using a thermoreversible gelation polymer (TGP) for 26 days were divided into three equal portions and 1.6 × 10 5 HCEP cells were injected on to the endothelium of the affected eye in each patient using the D25-NC gel sheet as a supporting material. The sheets were removed after three days. The bullae in the cornea disappeared by the 3 rd -11 th post-operative day in all the three patients. Visual acuity improved from Perception of light (PL)+/Projection of rays (PR)+ to Hand movements (HM)+ in one of the patients by post-operative day 3 which was maintained at 18 months follow-up. At 18 months follow-up, in another patient the visual acuity had improved from HM+ to 6/60 while in the third patient, visual acuity remained HM+ as it was prior to HCEP transplantation. There were no adverse effects during the follow-up in any of the patients.

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

Expression Analysis of the Transmembrane Mucin MUC20 in Human Corneal and Conjunctival Epithelia

PubMed Central

Woodward, Ashley M.; Argüeso, Pablo

2014-01-01

Purpose. Cell surface mucins are a group of highly O-glycosylated transmembrane glycoproteins responsible for the protection of epithelial cells on mucosal surfaces. The aim of this study was to investigate the localization and regulation of mucin 20 (MUC20) at the ocular surface. Methods. Localization of MUC20 in human corneal and conjunctival epithelia was evaluated by immunofluorescence microscopy. Immortalized corneal (HCLE) and conjunctival (HCjE) cell lines were grown at different stages of differentiation and subjected to quantitative PCR and Western blot analyses. Cell surface proteins on apical cell membranes were biotinylated and isolated by neutravidin chromatography. Results. The MUC20 was detected throughout the entire human ocular surface epithelia, predominantly in cell membranes within intermediate cell layers. In conjunctiva, MUC20 also was observed in the cytoplasm of apical cells within the stratified squamous epithelium, but not in goblet cells. Quantitative PCR and immunoblotting demonstrated expression of MUC20 in HCLE and HCjE cells. Induction of differentiation with serum-containing medium resulted in upregulation of MUC20 mRNA and protein. Biotin labeling of the surface of stratified cultures revealed low levels of MUC20 protein on apical glycocalyces. Further, MUC20 was not detected in the cell culture media or in human tears, suggesting that the extracellular domain of MUC20 is not released from the ocular surface as described previously for other cell surface mucins. Conclusions. Our results indicate that MUC20 is a novel transmembrane mucin expressed by the human corneal and conjunctival epithelia, and suggest that differential expression of MUC20 during differentiation has a role in maintaining ocular surface homeostasis. PMID:25168902

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

The central corneal light reflex ratio from photographs derived from a digital camera in young adults.

PubMed

Duangsang, Suampa; Tengtrisorn, Supaporn

2012-05-01

To determine the normal range of Central Corneal Light Reflex Ratio (CCLRR) from photographs of young adults. A digital camera equipped with a telephoto lens with a flash attachment placed directly above the lens was used to obtain corneal light reflex photographs of 104 subjects, first with the subject fixating on the lens of the camera at a distance of 43 centimeters, and then while looking past the camera to a wall at a distance of 5.4 meters. Digital images were displayed using Adobe Photoshop at a magnification of l200%. The CCLRR was the ratio of the sum of distances between the inner margin of cornea and the central corneal light reflex of each eye to the sum of horizontal corneal diameter of each eye. Measurements were made by three technicians on all subjects, and repeated on a 16% (n=17) subsample. Mean ratios (standard deviation-SD) from near/distance measurements were 0.468 (0.012)/0.452 (0.019). Limits of the normal range, with 95% certainty, were 0.448 and 0.488 for near measurements and 0.419 and 0.484 for distance measurements. Lower and upper indeterminate zones were 0.440-0.447 and 0.489-0.497 for near measurements and 0.406-0.418 and 0.485-0.497 for distance measurements. More extreme values can be considered as abnormal. The reproducibility and repeatability of the test was good. This method is easy to perform and has potential for use in strabismus screening by paramedical personnel.

[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.

Extracellular Collagen Promotes Interleukin-1β-Induced Urokinase-Type Plasminogen Activator Production by Human Corneal Fibroblasts.

PubMed

Sugioka, Koji; Kodama-Takahashi, Aya; Yoshida, Koji; Aomatsu, Keiichi; Okada, Kiyotaka; Nishida, Teruo; Shimomura, Yoshikazu

2017-03-01

Keratocytes maintain homeostasis of the corneal stroma through synthesis, secretion, and degradation of collagen fibrils of the extracellular matrix. Given that these cells are essentially embedded in a collagen matrix, keratocyte-collagen interactions may play a key role in regulation of the expression or activation of enzymes responsible for matrix degradation including urokinase-type plasminogen activator (uPA), plasmin, and matrix metalloproteinases (MMPs). We examined the effect of extracellular collagen on the production of uPA by corneal fibroblasts (activated keratocytes) stimulated with the proinflammatory cytokine interleukin-1β (IL-1β). Human corneal fibroblasts were cultured either on plastic or in a three-dimensional gel of type I collagen. Plasminogen activators were detected by fibrin zymography, whereas the IL-1 receptor (IL-1R) and MMPs were detected by immunoblot analysis. Collagen degradation by corneal fibroblasts was assessed by measurement of hydroxyproline in acid hydrolysates of culture supernatants. Collagen and IL-1β synergistically increased the synthesis and secretion of uPA in corneal fibroblasts. Collagen also upregulated IL-1R expression in the cells in a concentration-dependent manner. The conversion of extracellular plasminogen to plasmin, as well as the plasminogen-dependent activation of MMP-1 and MMP-3 and degradation of collagen apparent in three-dimensional cultures of corneal fibroblasts exposed to IL-1β, were all abolished by a selective uPA inhibitor. Collagen and IL-1β cooperate to upregulate uPA production by corneal fibroblasts. Furthermore, IL-1β-induced collagen degradation by these cells appears to be strictly dependent on uPA expression and mediated by a uPA-plasmin-MMP pathway.

Effect of different culture media and deswelling agents on survival of human corneal endothelial and epithelial cells in vitro.

PubMed

Valtink, Monika; Donath, Patricia; Engelmann, Katrin; Knels, Lilla

2016-02-01

To examine the effects of media and deswelling agents on human corneal endothelial and epithelial cell viability using a previously developed screening system. The human corneal endothelial cell line HCEC-12 and the human corneal epithelial cell line HCE-T were cultured in four different corneal organ culture media (serum-supplemented: MEM +2 % FCS, CorneaMax®/CorneaJet®, serum-free: Human Endothelial-SFM, Stemalpha-2 and -3) with and without 6 % dextran T500 or 7 % HES 130/0.4. Standard growth media F99HCEC and DMEM/F12HCE-T served as controls. In additional controls, the stress inducers staurosporine or hydrogen peroxide were added. After 5 days in the test media, cell viability was assessed by flow cytometrically quantifying apoptotic and necrotic cells (sub-G1 DNA content, vital staining with YO-PRO-1® and propidium iodide) and intracellular reactive oxygen species (ROS). The MEM-based media were unable to support HCEC-12 and HCE-T survival under stress conditions, resulting in significantly increased numbers of apoptotic and necrotic cells. HCEC-12 survival was markedly improved in SFM-based media even under staurosporine or hydrogen peroxide. Likewise, HCE-T survival was improved in SFM with or without dextran. The media CorneaMax®, CorneaJet®, and CorneaMax® with HES supported HCEC-12 survival better than MEM-based media, but less well than SFM-based media. HCE-T viability was also supported by CorneaJet®, but not by CorneaMax® with or without HES. Stemalpha-based media were not suitable for maintaining viability of HCEC-12 or HCE-T in the applied cell culture system. The use of serum-supplemented MEM-based media for corneal organ culture should be discontinued in favour of serum-free media like SFM.

Reconstruction of corneal epithelium with cryopreserved corneal limbal stem cells in a goat model.

PubMed

Mi, Shengli; Yang, Xueyi; Zhao, Qingmei; Qu, Lei; Chen, Shuming; M Meek, Keith; Dou, Zhongying

2008-11-01

We describe a procedure to construct an artificial corneal epithelium from cryopreserved limbal stem cells (LSCs) for corneal transplantation. The LSCs were separated from limbal tissue of male goats. The primary LSCs were identified by flow cytometry and were expanded. They were examined for stem cell-relevant properties and cryopreserved in liquid nitrogen. Cryopreserved LSCs were thawed and then transplanted onto human amniotic membrane, framed on a nitrocellulose sheet, to construct corneal epithelium sheets. The artificial corneal epithelium was transplanted into the right eye of pathological models of total limbal stem cell deficiency (LSCD). Then, the effects of reconstruction were evaluated by clinical observation and histological examination. Polymerase chain reaction analysis was used to detect the SRY gene. The data showed that transplantation of cryopreserved LSCs, like fresh LSCs, successfully reconstructed damaged goat corneal surface gradually, but the SRY gene expression from male goat cells could only be detected in the first 2 months after transplantation. The therapeutic effect of the transplantation may be associated with the inhibition of inflammation-related angiogenesis after transplantation of cryopreserved LSCs. This study provides the first line of evidence that cryopreserved LSCs can be used for reconstruction of damaged corneas, presenting a remarkable potential source for transplantation in the treatment of corneal disorders.

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.

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.

Matrix regeneration agents improve wound healing in non-stressed human corneal epithelial cells.

PubMed

Robciuc, A; Arvola, R P J; Jauhiainen, M; Holopainen, J M

2018-04-01

PurposeMatrix regenerating agents (RGTAs) emerged as promising in vivo wound-healing agents. These agents could prove beneficial for the treatment of dry eye disease-associated corneal micro-erosions; therefore, we aimed to evaluate the wound healing efficacy of regenerative agents (RGTAs or serum) in an in vitro model of hyperosmolarity (HO) stressed and non-stressed human corneal epithelial cells.Patients and methodsThe migration and proliferation induced by the regenerative agents was evaluated using an in vitro scratch wound assay and brome-deoxy-uridine incorporation. The inflammatory profile and effects of osmoregulators were also investigated. The two-tailed paired t-test calculated the statistical significance, with P-value<0.05 considered significant.ResultsThe most efficient inducer of re-epithelization was 2% serum, followed closely by 2% RGTA with an average improvement in cell migration of 1.8- and 1.4-fold, respectively, when compared with the non-treated control. Hyperosmolar stress significantly reduced the restorative effects of both serum and RGTAs; these effects were, however, neutralized by the osmoregulator betaine.ConclusionThese findings suggest that RGTAs could provide efficient treatment for dry-eye associated corneal micro-lesions if ocular surface HO is neutralized.

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.

Comparison of Corneal Biomechanical Properties between Indian and Chinese Adults.

PubMed

Chua, Jacqueline; Nongpiur, Monisha E; Zhao, Wanting; Tham, Yih Chung; Gupta, Preeti; Sabanayagam, Charumathi; Aung, Tin; Wong, Tien Yin; Cheng, Ching-Yu

2017-09-01

To investigate the difference in corneal hysteresis (CH) and corneal resistance factor (CRF) between Indian and Chinese populations. Population-based cross-sectional study. Three hundred eighty-two Singaporean Indian persons and 764 Singaporean Chinese 50 years of age or older were included from the Singapore Indian Eye Study and Singapore Chinese Eye Study, respectively. Participants underwent standardized systemic and ocular examinations and interviewer-administered questionnaires for risk factor assessment. The CH and CRF were measured with the Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, NY). Information on genetic ancestry was derived using principal component analysis. Linear regression models were used to investigate the association of CH and CRF with potential risk factors. Corneal hysteresis and CRF. After excluding participants with a history of intraocular surgery, a diagnosis of glaucoma suspect or glaucoma, refractive surgery, or presence of corneal abnormalities, CH and CRF readings were available for 382 Indian persons. For each Indian participant, 2 Chinese participants were selected and matched for age and gender (n = 764). There were no differences in the clinical measurements of CH (10.6±1.6 mmHg; P = 0.670) or CRF (10.3±1.7 mmHg; P = 0.103) between the ethnic groups. However, after adjusting for covariates, Indian persons had, on average, 0.18-mmHg higher CH levels than in Chinese (95% confidence interval [CI], 0.02-0.38; P = 0.031). Consistently, CH level was correlated significantly with genetic ancestry in the Southeast Asian population. Corneal resistance factor level was not associated independently with self-reported ethnicity (95% CI, -0.10 to 0.29; P = 0.335). Chinese have lower CH than Indian persons, and this disparity may reflect biomechanical differences of the cornea. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

"All-laser" endothelial corneal transplant in human patients

NASA Astrophysics Data System (ADS)

Rossi, Francesca; Menabuoni, Luca; Malandrini, Alex; Canovetti, Annalisa; Lenzetti, Ivo; Pini, Roberto

2012-03-01

Femtosecond laser sculpturing of corneal tissue is commonly used for the preparation of endothelial flaps. Diode laser welding of ocular tissues is a procedure that enables minimally invasive suturing of tissues. The combination of these laser based techniques results in a new approach to minimally invasive ophthalmic surgery, such as in endothelial corneal transplant (or endothelial keratoplasty - EK). In this work we present the "all laser" EK performed in human subjects. 24 pseudophakic patients with bullous keratopathy underwent EK: the femtosecond laser was used to prepare the 100 ìm thick and 8.5 mm diameter donor Descemet endothelial flap. After staining the stromal layer of the donor flap with a liquid ICG solution, the donor flap was inserted in the recipient eye by the use of the Busin injector. Then, the endothelial layer was laser-welded to the recipient eye (10 laser spots around the periphery of the flap), in order to reduce the risk of postoperative dislocation of the transplanted flap. A transplanted flap engraftment was observed in all the treated eyes. The staining procedure used to perform laser welding also enabled to evidence the stromal side of the donor flap, so as the flap was always placed in the right side position. The endothelial cells counts in both the laserwelded flaps and in a control group were in good agreement. The proposed technique is easy to perform and enables the reduction of postoperative endothelial flap dislocations.

Generation of Corneal Keratocytes from Human Embryonic Stem Cells.

PubMed

Hertsenberg, Andrew J; Funderburgh, James L

2016-01-01

Human Embryonic Stem Cells (hESC) offer an important resource as a limitless supply of any differentiated cell type of the human body. Keratocytes, cells from the corneal stroma, may have the potential for restoration of vision in cell therapy and biomedical engineering applications, but these specialized cells are not readily expanded in vitro. Here we describe a two-part method to produce keratocytes from the H1 hESC cell line. The hESC cells, maintained and expanded in feeder-free culture medium are first differentiated to neural crest cells using the stromal-derived inducing activity (SDIA) of the PA6 mouse embryonic fibroblast cell line. The resulting neural crest cells are selected by their expression of cell-surface CD271 and subsequently cultured as 3D pellets in a defined differentiation medium to induce a keratocyte phenotype.

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

Cell Homogeneity Indispensable for Regenerative Medicine by Cultured Human Corneal Endothelial Cells.

PubMed

Hamuro, Junji; Toda, Munetoyo; Asada, Kazuko; Hiraga, Asako; Schlötzer-Schrehardt, Ursula; Montoya, Monty; Sotozono, Chie; Ueno, Morio; Kinoshita, Shigeru

2016-09-01

To identify the subpopulation (SP) among heterogeneous cultured human corneal endothelial cells (cHCECs) devoid of cell-state transition applicable for cell-based therapy. Subpopulation presence in cHCECs was confirmed via surface CD-marker expression level by flow cytometry. CD markers effective for distinguishing distinct SPs were selected by analyzing those on established cHCECs with a small cell area and high cell density. Contrasting features among three typical cHCEC SPs was confirmed by PCR array for extracellular matrix (ECM). Combined analysis of CD markers was performed to identify the SP (effector cells) applicable for therapy. ZO-1 and Na+/K+ ATPase, CD200, and HLA expression were compared among heterogeneous SPs. Flow cytometry analysis identified the effector cell expressing CD166+CD105-CD44-∼+/-CD26-CD24-, but CD200-, and the presence of other SPs with CD166+ CD105-CD44+++ (CD26 and CD24, either + or -) was confirmed. PCR array revealed three distinct ECM expression profiles. Some SPs expressed ZO-1 and Na+/K+ ATPase at comparable levels with effector cells, while only one SP expressed CD200, but not on effector cells. Human leukocyte antigen expression was most reduced in the effector SP. The proportion of effector cells (E-ratio) inversely paralleled donor age and decreased during prolonged culture passages. The presence of Rho-associated protein kinase (ROCK) inhibitor increased the E-ratio in cHCECs. The average area of effector cells was approximately 200∼220 μm2, and the density of cHCECs exceeded 2500 cells/mm2. A specified cultured effector cell population sharing the surface phenotypes with mature HCECs in corneal tissues may serve as an alternative to donor corneas for the treatment of corneal endothelial dysfunction.

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.

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.

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.

Human cadaver retina model for retinal heating during corneal surgery with a femtosecond laser

NASA Astrophysics Data System (ADS)

Sun, Hui; Fan, Zhongwei; Yun, Jin; Zhao, Tianzhuo; Yan, Ying; Kurtz, Ron M.; Juhasz, Tibor

2014-02-01

Femtosecond lasers are widely used in everyday clinical procedures to perform minimally invasive corneal refractive surgery. The intralase femtosecond laser (AMO Corp. Santa Ana, CA) is a common example of such a laser. In the present study a numerical simulation was developed to quantify the temperature rise in the retina during femtosecond intracorneal surgery. Also, ex-vivo retinal heating due to laser irradiation was measured with an infrared thermal camera (Fluke Corp. Everett, WA) as a validation of the simulation. A computer simulation was developed using Comsol Multiphysics to calculate the temperature rise in the cadaver retina during femtosecond laser corneal surgery. The simulation showed a temperature rise of less than 0.3 degrees for realistic pulse energies for the various repetition rates. Human cadaver retinas were irradiated with a 150 kHz Intralase femtosecond laser and the temperature rise was measured withan infrared thermal camera. Thermal camera measurements are in agreement with the simulation. During routine femtosecond laser corneal surgery with normal clinical parameters, the temperature rise is well beneath the threshold for retina damage. The simulation predictions are in agreement with thermal measurements providing a level of experimental validation.

Rapid, automated mosaicking of the human corneal subbasal nerve plexus.

PubMed

Vaishnav, Yash J; Rucker, Stuart A; Saharia, Keshav; McNamara, Nancy A

2017-11-27

Corneal confocal microscopy (CCM) is an in vivo technique used to study corneal nerve morphology. The largest proportion of nerves innervating the cornea lie within the subbasal nerve plexus, where their morphology is altered by refractive surgery, diabetes and dry eye. The main limitations to clinical use of CCM as a diagnostic tool are the small field of view of CCM images and the lengthy time needed to quantify nerves in collected images. Here, we present a novel, rapid, fully automated technique to mosaic individual CCM images into wide-field maps of corneal nerves. We implemented an OpenCV image stitcher that accounts for corneal deformation and uses feature detection to stitch CCM images into a montage. The method takes 3-5 min to process and stitch 40-100 frames on an Amazon EC2 Micro instance. The speed, automation and ease of use conferred by this technique is the first step toward point of care evaluation of wide-field subbasal plexus (SBP) maps in a clinical setting.

Optimized human platelet lysate as novel basis for a serum-, xeno-, and additive-free corneal endothelial cell and tissue culture.

PubMed

Thieme, Daniel; Reuland, Lynn; Lindl, Toni; Kruse, Friedrich; Fuchsluger, Thomas

2018-02-01

The expansion of donor-derived corneal endothelial cells (ECs) is a promising approach for regenerative therapies in corneal diseases. To achieve the best Good Manufacturing Practice standard the entire cultivation process should be devoid of nonhuman components. However, so far, there is no suitable xeno-free protocol for clinical applications. We therefore introduce a processed variant of a platelet lysate for the use in corneal cell and tissue culture based on a Good Manufacturing Practice-grade thrombocyte concentrate. This processed human platelet lysate (phPL), free of any animal components and of anticoagulants such as heparin with a physiological ionic composition, was used to cultivate corneal ECs in vitro and ex vivo in comparison to standard cultivation with fetal calf serum (FCS). Human donor corneas were cut in quarters while 2 quarters of each cornea were incubated with the respective medium supplement. Three fields of view per quarter were taken into account for the analysis. Evaluation of phPL as a medium supplement in cell culture of immortalized EC showed a superior viability compared with FCS control with reduced cell proliferation. Furthermore, the viability during the expansion of primary cells is significantly (3-fold ±0.5) increased with phPL compared with FCS standard medium. Quartering donor corneas was traumatic for the endothelium and therefore resulted in increased EC loss. Interestingly, however, cultivation of the quartered pieces for 2 weeks in 0.1-mg/ml pHPL in Biochrome I showed a 21 (±10) % EC loss compared with 67 (±12) % EC loss when cultivated in 2% FCS in Biochrome I. The cell culture protocol with pHPL as FCS replacement seems to be superior to the standard FCS protocols with respect to EC survival. It offers a xeno-free and physiological environment for corneal endothelial cells. This alternative cultivation protocol could facilitate the use of EC for human corneal cell therapy. Copyright © 2017 John Wiley & Sons, Ltd.

In vitro effects of three blood derivatives on human corneal epithelial cells.

PubMed

Freire, Vanesa; Andollo, Noelia; Etxebarria, Jaime; Durán, Juan A; Morales, María-Celia

2012-08-15

We compared the effects of three blood derivatives, autologous serum (AS), platelet-rich plasma (PRP), and serum derived from plasma rich in growth factors (PRGF), on a human corneal epithelial (HCE) cell line to evaluate their potential as an effective treatment for corneal epithelial disorders. The concentrations of epidermal growth factor (EGF), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF), and fibronectin were quantified by ELISA. The proliferation and viability of HCE cells were measured by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric assay. Cell morphology was assessed by phase-contrast microscopy. The patterns of expression of several connexin, involucrin, and integrin α6 genes were analyzed by real-time RT-PCR. We found significantly higher levels of EGF in PRGF compared to AS and PRP. However, AS and PRGF induced robust proliferation of HCE cells. In addition, PRGF cultured cells grew as heterogeneous colonies, exhibiting differentiated and non-differentiated cell phenotypes, whereas AS- and PRP-treated cultures exhibited quite homogeneous colonies. Finally, PRGF upregulated the expression of several genes associated with communication and cell differentiation, in comparison to AS or PRP. PRGF promotes biological processes required for corneal epithelialization, such as proliferation and differentiation. Since PRGF effects are similar to those associated with routinely used blood derivatives, the present findings warrant further research on PRGF as a novel alternative treatment for ocular surface diseases.

Centennial review of corneal transplantation.

PubMed

Moffatt, S Louise; Cartwright, Victoria A; Stumpf, Thomas H

2005-12-01

Abstract One hundred years ago, on 7 December 1905, Dr Eduard Zirm performed the world's first successful human corneal transplant. This significant milestone was achieved only after many decades of unsuccessful trial and error; however, it did not lead to relatively 'routine' keratoplasty success for several more decades. The idea of replacing an opaque cornea had been suggested for centuries, and had stimulated theoretical approaches to the problem by many esteemed physicians throughout history. However, little practical progress was made in the ultimate realization of the dream until the 19th century when pioneering surgeons pursued extensive studies in relation to both animal and human 'keratoplasty'. Clinical progress and scientific insight developed slowly, and it was ultimately due to parallel advances in medicine such as anaesthesia and antisepsis that Zirm's success was finally achieved. Key concepts were enshrined such as the use of fresh tissue from the same species, careful placement and handling of tissue, and the development of specialized instrumentation such as the circular trephine. In the latter half of the 20th century, many 'masters' of corneal surgery evolved significant refinements in technique and instrumentation with the development of corticosteroids, antibiotics, surgical microscopes, improved trephines, viscoelastics and suture materials, that enable this delicate procedure to be routinely performed with the prospect of success. There are still limitations to corneal transplantation, and corneal allograft rejection still poses the greatest challenge to the modern corneal surgeon. In the foreseeable future it may be in the laboratory, rather than the theatre, that further milestones will be achieved. This review aims to highlight the significant milestones in the rich history of corneal transplantation, and to pay tribute to the many inspired and dedicated individuals involved in the development of keratoplasty to a point where the

Cytotoxicity of lidocaine to human corneal endothelial cells in vitro.

PubMed

Yu, Hao-Ze; Li, Yi-Han; Wang, Rui-Xin; Zhou, Xin; Yu, Miao-Miao; Ge, Yuan; Zhao, Jun; Fan, Ting-Jun

2014-04-01

Lidocaine has been reported to induce apoptosis on rabbit corneal endothelial cells. However, the apoptotic effect and exact mechanism involved in cytotoxicity of lidocaine are not well-established in human corneal endothelial (HCE) cells. In this study, we investigated the apoptosis-inducing effect of lidocaine on HCE cells in vitro. After HCE cells were treated with lidocaine at concentrations of 0.15625-10.0 g/l, the morphology and ultrastructure of the cells were observed by inverted light microscope and transmission electron microscope (TEM). Cell viability was measured by MTT assay, and the apoptotic ratio was evaluated with flow cytometry and fluorescent microscopic counting after FITC-Annexin V/PI and AO/EB staining. DNA fragmentation was detected by electrophoresis, and the activation of caspases was evaluated by ELISA. In addition, changes in mitochondrial membrane potential were determined by JC-1 staining. Results suggest that lidocaine above 1.25 g/l reduced cellular viability and triggered apoptosis in HCE cells in a time- and dose-dependent manner. Diminishment of ΔΨm and the activation of caspases indicate that lidocaine-induced apoptosis was caspase dependent and may be related to mitochondrial pathway. © 2013 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Establishment of a new immortalized human corneal epithelial cell line (iHCE-NY1) for use in evaluating eye irritancy by in vitro test methods.

PubMed

Yamamoto, Naoki; Kato, Yoshinao; Sato, Atsushi; Hiramatsu, Noriko; Yamashita, Hiromi; Ohkuma, Mahito; Miyachi, Ei-Ichi; Horiguchi, Masayuki; Hirano, Koji; Kojima, Hajime

2016-08-01

In vitro test methods that use human corneal epithelial cells to evaluate the eye irritation potency of chemical substances do not use human corneal epithelium because it has been difficult to maintain more than four passages. In this study, we make a new cell line comprising immortalized human corneal epithelial cells (iHCE-NY1). The IC50 of iHCE-NY1 cells is slightly higher than that of Statens Seruminstitut Rabbit Cornea (SIRC) cells, which are currently used in some in vitro test methods. CDKN1A in iHCE-NY1 cells was used as a marker of gene expression to indicate cell cycle activity. This enabled us to evaluate cell recovery characteristics at concentrations lower than the IC50 of cytotoxic tests.

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.

Interferometer for measuring dynamic corneal topography

NASA Astrophysics Data System (ADS)

Micali, Jason Daniel

The cornea is the anterior most surface of the eye and plays a critical role in vision. A thin fluid layer, the tear film, coats the outer surface of the cornea and serves to protect, nourish, and lubricate the cornea. At the same time, the tear film is responsible for creating a smooth continuous surface where the majority of refraction takes place in the eye. A significant component of vision quality is determined by the shape of the cornea and stability of the tear film. It is desirable to possess an instrument that can measure the corneal shape and tear film surface with the same accuracy and resolution that is currently performed on common optical elements. A dual interferometer system for measuring the dynamic corneal topography is designed, built, and verified. The completed system is validated by testing on human subjects. The system consists of two co-aligned polarization splitting Twyman-Green interferometers designed to measure phase instantaneously. The primary interferometer measures the surface of the tear film while the secondary interferometer simultaneously tracks the absolute position of the cornea. Eye motion, ocular variation, and a dynamic tear film surface will result in a non-null configuration of the surface with respect to the interferometer system. A non-null test results in significant interferometer induced errors that add to the measured phase. New algorithms are developed to recover the absolute surface topography of the tear film and corneal surface from the simultaneous interferometer measurements. The results are high-resolution and high-accuracy surface topography measurements of the in vivo cornea that are captured at standard camera frame rates. This dissertation will cover the development and construction of an interferometer system for measuring the dynamic corneal topography of the human eye. The discussion starts with the completion of an interferometer for measuring the tear film. The tear film interferometer is part of an

Time course of the effects of orthokeratology on peripheral refraction and corneal topography.

PubMed

Kang, Pauline; Swarbrick, Helen

2013-05-01

To describe the time course of changes in both peripheral refraction and corneal topography in myopic adults wearing myopic orthokeratology (OK) lenses. Nineteen adult myopes were fitted with OK lenses in both eyes for overnight wear. Central and peripheral refraction and corneal topography were measured along the horizontal meridian at baseline and after 1, 4, 7 and 14 nights of lens wear. At baseline, refraction was myopic at all positions along the horizontal meridian. Two weeks of OK lens wear caused a significant change in refraction where the general trend was a hyperopic shift in spherical equivalent (M) except at 35° in the nasal visual field where there was instead a myopic shift in M. The most significant change in M occurred between baseline and after 1 night of OK lens wear and the effect became less dramatic across subsequent days of OK treatment. Similarly, OK caused significant change in corneal refractive power at all positions along the horizontal corneal chord. There was a reduction in corneal power or flattening of the cornea at all positions except at 2.4 mm and 2.8 mm on the nasal cornea where there was an increase in corneal refractive power or steepening of the cornea. This change was most apparent after 1 night of OK lens wear and, similar to changes in peripheral refraction, changes in corneal refractive power on subsequent days of OK treatment became less marked. Orthokeratology caused significant changes in both peripheral refraction and corneal topography. The greatest change in refraction and corneal refractive power across the horizontal corneal meridian occurred during the first night of OK lens wear. Subsequent changes in both peripheral refraction and corneal topography were less dramatic, in the same manner as reported changes in apical radius and central refraction after OK. This study confirms that with OK treatment, the peripheral retina experiences myopic defocus, which is conjectured to underlie the observed slowing of myopia

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

Corneal thickness: measurement and implications.

PubMed

Ehlers, Niels; Hjortdal, Jesper

2004-03-01

The thickness of the cornea was reported in more than 100-year-old textbooks on physiological optics (Helmholtz, Gullstrand). Physiological interest was revived in the 1950s by David Maurice, and over the next 50 years, this 'simple' biological parameter has been studied extensively. Several techniques for its measurement have been described and physiological and clinical significance have been studied. In this review, the different methods and techniques of measurement are briefly presented (optical, ultrasound). While the corneal thickness of many animals are the same over a considerable part of the surface, in the human cornea anterior and posterior curvature are not concentric giving rise to a problem of definition. Based on this the precision and accuracy of determining the central corneal thickness are discussed. Changes in corneal thickness reflects changes in function of the boundary layers, in particular the endothelial barrier. The absolute value of thickness is of importance for the estimation of IOP but also in diagnosis of corneal and systemic disorders. Finally it is discussed to what extent the thickness is a biometric parameter of significance, e.g. in the progression of myopia or in the development of retinal detachment.

Topical NSAIDs effect on corneal sensitivity.

PubMed

Singer, Daniel D; Kennedy, John; Wittpenn, John R

2015-05-01

Topical nonsteroidal antiinflammatory drugs (NSAIDs) are administered topically for a variety of ophthalmologic conditions. Brand diclofenac and brand ketorolac were previously shown to have topical anesthetic effects in addition to analgesic effects. Using the same method, we measured similar anesthetic effects of the 4 currently available topical NSAIDs--generic diclofenac, generic ketorolac, brand bromfenac, and brand nepafenac. Baseline corneal sensitivity was measured on 10 healthy adult volunteers with a Cochet-Bonnet esthesiometer. One drop of the agent being studied was applied to the right eye every 5 minutes for a total of 4 drops. Corneal sensitivity was measured immediately after the last topical application and every 15 minutes for 60 minutes. After a 1-week washout period, a different agent was studied until all 4 NSAIDs were evaluated. Corneal sensitivity profiles over time were similar for all NSAIDs. Corneal sensitivity decreased significantly from baseline immediately after topical application remaining flat from 0 to 30 minutes and then rising from 45 to 60 minutes back toward baseline in all treatment groups (P < 0.001). The maximal absolute drop in corneal sensitivity as measured by pressure thresholds was greatest for diclofenac [28.6 mm (95% confidence intervals {CI}, 19.8-37.4)], followed by ketorolac [21.1 mm (95% CI, 15.1-27.1)], bromfenac [16.9 mm (10.7-23.1)], and nepafenac [16.4 mm (95% CI, 12.7-20.1)]. Only diclofenac and nepafenac were statistically different in maximal decrease in sensitivity. All 4 currently available NSAIDs demonstrated anesthetic effects similar to brand diclofenac and brand ketorolac.

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.

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.

Collagen VII deficient mice show morphologic and histologic corneal changes that phenotypically mimic human dystrophic epidermolysis bullosa of the eye.

PubMed

Chen, Vicki M; Shelke, Rajani; Nyström, Alexander; Laver, Nora; Sampson, James F; Zhiyi, Cao; Bhat, Najma; Panjwani, Noorjahan

2018-06-16

Absence of collagen VII causes blistering of the skin, eyes and many other tissues. This disease is termed dystrophic epidermolysis bullosa (DEB). Corneal fibrosis occurs in up to 41% and vision loss in up to 64% of patients. Standard treatments are supportive and there is no cure. The immune-histologic and morphologic changes in the corneas of the mouse model for this disease have not been described in the literature. Our purpose is to characterize the eyes of these mice to determine if this is an appropriate model for study of human therapeutics. Western blot analysis (WB) and immunohistochemistry (IHC) were performed to assess the relative collagen VII protein levels and its location within the cornea. Additional IHC for inflammatory and fibrotic biomarkers alpha-smooth muscle actin (α-SMA), transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), proteinase 3, tenascin C and collagen III were performed. Clinical photographs documenting opacification of the corneas of animals of differing ages were assessed and scored independently by 2 examiners. Histology was then used to investigate morphologic changes. IHC and WB confirmed that these mice are deficient in collagen VII production at the level of the basement membrane when compared with wild-types. IHC showed anomalous deposition of collagen III throughout the stroma. Of the 5 biomarkers tested, TGF-β showed the strongest and most consistently staining. Photographs documented corneal opacities only in mice older than 10 weeks, opacities were not seen in younger animals. Histology showed multiple abnormalities, including epithelial hyperplasia, ulceration, fibrosis, edema, dysplasia, neovascularization and bullae formation. The collagen VII hypomorphic mouse shows reduced collagen VII production at the level of the corneal basement membrane. Corneal changes are similar to pathology seen in humans with this disease. The presence of anomalous stromal collagen III and TGF-β appear to be

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.

Analysis of sphingolipids in human corneal fibroblasts from normal and keratoconus patients[S

PubMed Central

Qi, Hui; Priyadarsini, Shrestha; Nicholas, Sarah E.; Sarker-Nag, Akhee; Allegood, Jeremy; Chalfant, Charles E.; Mandal, Nawajes A.; Karamichos, Dimitrios

2017-01-01

The pathophysiology of human keratoconus (KC), a bilateral progressive corneal disease leading to protrusion of the cornea, stromal thinning, and scarring, is not well-understood. In this study, we investigated a novel sphingolipid (SPL) signaling pathway through which KC may be regulated. Using human corneal fibroblasts (HCFs) and human KC cells (HKCs), we examined the SPL pathway modulation. Both cell types were stimulated by the three transforming growth factor (TGF)-β isoforms: TGF-β1 (T1), TGF-β2 (T2), and TGF-β3 (T3). All samples were analyzed using lipidomics and real-time PCR. Our data showed that HKCs have increased levels of signaling SPLs, ceramide (Cer), and sphingosine 1-phosphate (S1P). Treatment with T1 reversed the increase in Cer in HKCs and treatment with T3 reversed the increase in S1P. S1P3 receptor mRNA levels were also significantly upregulated in HKCs, but were reduced to normal levels following T3 treatment. Furthermore, stimulation with Cer and S1P led to significant upregulation of fibrotic markers in HCFs, but not in HKCs. Additionally, stimulation with a Cer synthesis inhibitor (FTY720) led to significant downregulation of specific fibrotic markers in HKCs (TGF-β1, collagen type III, and α smooth muscle actin) without an effect on healthy HCFs, suggesting a causative role of Cer and S1P in fibrogenesis. Overall, this study suggests an association of the SPL signaling pathway in KC disease and its relation with the TGF-β pathway. PMID:28188148

[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.

Therapeutic Effect of Human Adipose Tissue-Derived Mesenchymal Stem Cells in Experimental Corneal Failure Due to Limbal Stem Cell Niche Damage.

PubMed

Galindo, Sara; Herreras, José M; López-Paniagua, Marina; Rey, Esther; de la Mata, Ana; Plata-Cordero, María; Calonge, Margarita; Nieto-Miguel, Teresa

2017-10-01

Limbal stem cells are responsible for the continuous renewal of the corneal epithelium. The destruction or dysfunction of these stem cells or their niche induces limbal stem cell deficiency (LSCD) leading to visual loss, chronic pain, and inflammation of the ocular surface. To restore the ocular surface in cases of bilateral LSCD, an extraocular source of stem cells is needed to avoid dependence on allogeneic limbal stem cells that are difficult to obtain, isolate, and culture. The aim of this work was to test the tolerance and the efficacy of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) to regenerate the ocular surface in two experimental models of LSCD that closely resemble different severity grades of the human pathology. hAT-MSCs transplanted to the ocular surface of the partial and total LSCD models developed in rabbits were well tolerated, migrated to inflamed tissues, reduced inflammation, and restrained the evolution of corneal neovascularization and corneal opacity. The expression profile of the corneal epithelial cell markers CK3 and E-cadherin, and the limbal epithelial cell markers CK15 and p63 was lost in the LSCD models, but was partially recovered after hAT-MSC transplantation. For the first time, we demonstrated that hAT-MSCs improve corneal and limbal epithelial phenotypes in animal LSCD models. These results support the potential use of hAT-MSCs as a novel treatment of ocular surface failure due to LSCD. hAT-MSCs represent an available, non-immunogenic source of stem cells that may provide therapeutic benefits in addition to reduce health care expenses. Stem Cells 2017;35:2160-2174. © 2017 AlphaMed Press.

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

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.

Upregulated epidermal growth factor receptor expression following near-infrared irradiation simulating solar radiation in a three-dimensional reconstructed human corneal epithelial tissue culture model

PubMed Central

Tanaka, Yohei; Nakayama, Jun

2016-01-01

Background and objective Humans are increasingly exposed to near-infrared (NIR) radiation from both natural (eg, solar) and artificial (eg, electrical appliances) sources. Although the biological effects of sun and ultraviolet (UV) exposure have been extensively investigated, the biological effect of NIR radiation is still unclear. We previously reported that NIR as well as UV induces photoaging and standard UV-blocking materials, such as sunglasses, do not sufficiently block NIR. The objective of this study was to investigate changes in gene expression in three-dimensional reconstructed corneal epithelial tissue culture exposed to broad-spectrum NIR irradiation to simulate solar NIR radiation that reaches human tissues. Materials and methods DNA microarray and quantitative real-time polymerase chain reaction analysis were used to assess gene expression levels in a three-dimensional reconstructed corneal epithelial model composed of normal human corneal epithelial cells exposed to water-filtered broad-spectrum NIR irradiation with a contact cooling (20°C). The water-filter allowed 1,000–1,800 nm wavelengths and excluded 1,400–1,500 nm wavelengths. Results A DNA microarray with >62,000 different probes showed 25 and 150 genes that were up- or downregulated by at least fourfold and twofold, respectively, after NIR irradiation. In particular, epidermal growth factor receptor (EGFR) was upregulated by 19.4-fold relative to control cells. Quantitative real-time polymerase chain reaction analysis revealed that two variants of EGFR in human corneal epithelial tissue were also significantly upregulated after five rounds of 10 J/cm2 irradiation (P<0.05). Conclusion We found that NIR irradiation induced the upregulated expression of EGFR in human corneal cells. Since over half of the solar energy reaching the Earth is in the NIR region, which cannot be adequately blocked by eyewear and thus can induce eye damage with intensive or long-term exposure, protection from both

Upregulated epidermal growth factor receptor expression following near-infrared irradiation simulating solar radiation in a three-dimensional reconstructed human corneal epithelial tissue culture model.

PubMed

Tanaka, Yohei; Nakayama, Jun

2016-01-01

Humans are increasingly exposed to near-infrared (NIR) radiation from both natural (eg, solar) and artificial (eg, electrical appliances) sources. Although the biological effects of sun and ultraviolet (UV) exposure have been extensively investigated, the biological effect of NIR radiation is still unclear. We previously reported that NIR as well as UV induces photoaging and standard UV-blocking materials, such as sunglasses, do not sufficiently block NIR. The objective of this study was to investigate changes in gene expression in three-dimensional reconstructed corneal epithelial tissue culture exposed to broad-spectrum NIR irradiation to simulate solar NIR radiation that reaches human tissues. DNA microarray and quantitative real-time polymerase chain reaction analysis were used to assess gene expression levels in a three-dimensional reconstructed corneal epithelial model composed of normal human corneal epithelial cells exposed to water-filtered broad-spectrum NIR irradiation with a contact cooling (20°C). The water-filter allowed 1,000-1,800 nm wavelengths and excluded 1,400-1,500 nm wavelengths. A DNA microarray with >62,000 different probes showed 25 and 150 genes that were up- or downregulated by at least fourfold and twofold, respectively, after NIR irradiation. In particular, epidermal growth factor receptor (EGFR) was upregulated by 19.4-fold relative to control cells. Quantitative real-time polymerase chain reaction analysis revealed that two variants of EGFR in human corneal epithelial tissue were also significantly upregulated after five rounds of 10 J/cm(2) irradiation (P<0.05). We found that NIR irradiation induced the upregulated expression of EGFR in human corneal cells. Since over half of the solar energy reaching the Earth is in the NIR region, which cannot be adequately blocked by eyewear and thus can induce eye damage with intensive or long-term exposure, protection from both UV and NIR radiation may prevent changes in gene expression and in

[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

Corneal Tissue Engineering: Recent Advances and Future Perspectives

PubMed Central

Ghezzi, Chiara E.; Rnjak-Kovacina, Jelena

2015-01-01

To address the growing need for corneal transplants two main approaches are being pursued: allogenic and synthetic materials. Allogenic tissue from human donors is currently the preferred choice; however, there is a worldwide shortage in donated corneal tissue. In addition, tissue rejection often limits the long-term success of this approach. Alternatively, synthetic homologs to donor corneal grafts are primarily considered temporary replacements until suitable donor tissue becomes available, as they result in a high incidence of graft failure. Tissue engineered cornea analogs would provide effective cornea tissue substitutes and alternatives to address the need to reduce animal testing of commercial products. Recent progress toward these needs is reviewed here, along with future perspectives. PMID:25434371

CTCF-Mediated and Pax6-Associated Gene Expression in Corneal Epithelial Cell-Specific Differentiation

PubMed Central

Tsui, Shanli; Wang, Jie; Wang, Ling; Dai, Wei; Lu, Luo

2016-01-01

Background The purpose of the study is to elicit the epigenetic mechanism involving CCCTC binding factor (CTCF)-mediated chromatin remodeling that regulates PAX6 gene interaction with differentiation-associated genes to control corneal epithelial differentiation. Methods Cell cycle progression and specific keratin expressions were measured to monitor changes of differentiation-induced primary human limbal stem/progenitor (HLS/P), human corneal epithelial (HCE) and human telomerase-immortalized corneal epithelial (HTCE) cells. PAX6-interactive and differentiation-associated genes in chromatin remodeling mediated by the epigenetic factor CTCF were detected by circular chromosome conformation capture (4C) and ChIP (Chromatin immunoprecipitation)-on-chip approaches, and verified by FISH (Fluorescent in situ hybridization). Furthermore, CTCF activities were altered by CTCF-shRNA to study the effect of CTCF on mediating interaction of Pax6 and differentiation-associated genes in corneal epithelial cell fate. Results Our results demonstrated that differentiation-induced human corneal epithelial cells expressed typical corneal epithelial characteristics including morphological changes, increased keratin12 expression and G0/G1 accumulations. Expressions of CTCF and PAX6 were suppressed and elevated following the process of differentiation, respectively. During corneal epithelial cell differentiation, differentiation-induced RCN1 and ADAM17 were found interacting with PAX6 in the process of CTCF-mediated chromatin remodeling detected by 4C and verified by ChIP-on-chip and FISH. Diminished CTCF mRNA with CTCF-shRNA in HTCE cells weakened the interaction of PAX6 gene in controlling RCN1/ADAM17 and enhanced early onset of the genes in cell differentiation. Conclusion Our results explain how epigenetic factor CTCF-mediated chromatin remodeling regulates interactions between eye-specific PAX6 and those genes that are induced/associated with cell differentiation to modulate

Anti-CD40 antibody-mediated costimulation blockade promotes long-term survival of deep-lamellar porcine corneal grafts in non-human primates.

PubMed

Kim, Jaeyoung; Kim, Dong Hyun; Choi, Hyuk Jin; Lee, Hyun Ju; Kang, Hee Jung; Park, Chung-Gyu; Hwang, Eung-Soo; Kim, Mee Kum; Wee, Won Ryang

2017-05-01

Corneal xenotransplantation is an effective solution for the shortage of human donor corneas, and the porcine cornea may be a suitable candidate for the donor cornea because of its optical similarity with humans. However, it is necessary to administer additional immunosuppressants to overcome antigenic differences. We aimed to investigate the feasibility of porcine corneas with anti-CD40 antibody-mediated costimulation blockade in a clinically applicable pig-to-non-human primate corneal xenotransplantation model. Five Chinese rhesus macaques underwent deep-lamellar corneal transplantation using clinically acceptable sized (7.5 mm diameter) porcine corneal grafts. The anti-CD40 antibody was intravenously administered on a programmed schedule. Graft survival, central corneal thickness, and intraocular pressure were evaluated. Changes in effector and memory T and B cell subsets and anti-αGal and donor-specific antibodies were investigated in the blood, and the changes in complement levels in the aqueous humor and blood were evaluated. Memory cell profiles in the anti-CD40 antibody-treated group were compared with those from the anti-CD154 antibody-treated group or rejected controls presented in our previous report. The changes in anti-αGal, non-αGal, and donor-specific antibodies after 6 months were compared with baseline values. Anti-CD40 antibody-mediated costimulation blockade resulted in the successful survival of xenocorneal grafts (>389, >382, >236, >201, and >61 days), with 80% reaching 6 months of survival. Injection of anti-CD40 antibody considerably reduced the infiltration of inflammatory cells into the grafts and significantly blocked the complement response in the aqueous humor (P=.0159, Mann-Whitney U test). Systemic expansion of central or effector memory T cells was abrogated in the anti-CD40 antibody-treated primates compared with those in the rejected controls (P<.05, Mann-Whitney U test) or those in the anti-CD154 antibody-treated primates (P

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.

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

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.

High molecular weight hyaluronan decreases oxidative DNA damage induced by EDTA in human corneal epithelial cells

PubMed Central

Ye, J; Wu, H; Wu, Y; Wang, C; Zhang, H; Shi, X; Yang, J

2012-01-01

Purpose To investigate the toxic effects of ethylenediaminetetraacetic acid disodium salt (EDTA), a corneal penetration enhancer in topical ophthalmic formulations, on DNA in human corneal epithelial cells (HCEs), and to investigate whether the effect induced by EDTA can be inhibited by high molecular weight hyaluronan (HA). Methods Cells were exposed to EDTA in concentrations ranging from 0.00001 to 0.01% for 60 min, or 30 min high molecular weight HA pretreatment followed by EDTA treatment. The cell viability was measured by the MTT test. Cell apoptosis was determined with annexin V staining by flow cytometry. The DNA single- and double-strand breaks of HCEs were examined by alkaline comet assay and by immunofluorescence microscope detection of the phosphorylated form of histone variant H2AX (γH2AX) foci, respectively. Reactive oxygen species (ROS) production was assessed by the fluorescent probe, 2′, 7′-dichlorodihydrofluorescein diacetate. Results EDTA exhibited no adverse effect on cell viability and did not induce cell apoptosis in human corneal epithelial cells at concentrations lower than 0.01%. However, a significant increase of DNA single- and double-strand breaks was observed in a dose-dependent manner with all the concentrations of EDTA tested in HCEs. In addition, EDTA treatment led to elevated ROS generation. Moreover, 30 min preincubation with high molecular weight HA significantly decreased EDTA-induced ROS generation and DNA damage. Conclusions EDTA could induce DNA damage in HCEs, probably through oxidative stress. Furthermore, high molecular weight HA was an effective protective agent that had antioxidant properties and decreased DNA damage induced by EDTA. PMID:22595911

Corneal collagen cross-linking: a confocal, electron, and light microscopy study of eye bank corneas.

PubMed

Dhaliwal, Jasmeet S; Kaufman, Stephen C

2009-01-01

The purpose of this study was to evaluate morphological changes induced by corneal collagen cross-linking in a human ex vivo cornea, using confocal, electron, and light microscopy. The central epithelium was partially removed from ex vivo human corneal buttons. Riboflavin 0.1% solution was applied before ultraviolet A light treatment and then for every 2 minutes for 30 minutes while the corneas were exposed to ultraviolet A light at a wavelength of 370 nm and intensity of 3 mW/cm(2). Each cornea was evaluated using confocal, electron, and light microscopy. Confocal microscopy demonstrated normal-appearing corneas on their initial pretreatment examination, with reduced stromal detail. After treatment, a superficial layer of highly reflective spherical structures (4-10 microm) was observed. Many of these hyperreflective structures appeared up to a depth of 300 microm. The remainder of the corneal stroma and endothelium appeared normal. Electron microscopy showed keratocyte apoptotic changes to a depth of 300 microm. No observable pathologic changes were seen on histology. Based on clinical studies, corneal cross-linking is a promising treatment that appears to be safe and to halt ectatic corneal disease progression. Initial European studies used animal models to extrapolate human protocols. In conjunction with clinical studies, we believe that human ex vivo corneal studies provide a means to evaluate the structural and morphological changes associated with this procedure, within human corneas, in a manner that cannot be accomplished in vivo.

Human Corneal Limbal-Epithelial Cell Response to Varying Silk Film Geometric Topography In Vitro

PubMed Central

Lawrence, Brian D.; Pan, Zhi; Liu, Aihong; Kaplan, David L.; Rosenblatt, Mark I.

2012-01-01

Silk fibroin films are a promising class of biomaterials that have a number of advantages for use in ophthalmic applications due to their transparent nature, mechanical properties and minimal inflammatory response upon implantation. Freestanding silk films with parallel line and concentric ring topographies were generated for in vitro characterization of human corneal limbal-epithelial (HCLE) cell response upon differing geometric patterned surfaces. Results indicated that silk film topography significantly affected initial HCLE culture substrate attachment, cellular alignment, cell-to-cell contact formation, actin cytoskeleton alignment, and focal adhesion (FA) localization. Most notably, parallel line patterned surfaces displayed a 36%–54% increase on average in initial cell attachment, which corresponded to an over 2-fold increase in FA localization when compared to other silk film surfaces and controls. In addition, distinct localization of FA formation was observed along the edges for all patterned silk film topographies. In conclusion, silk film feature topography appears to help direct corneal epithelial cell response and cytoskeleton development, especially in regards to FA distribution, in vitro. PMID:22705042

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.

Compressed Collagen Enhances Stem Cell Therapy for Corneal Scarring

PubMed Central

Shojaati, Golnar; Khandaker, Irona; Sylakowski, Kyle; Funderburgh, Martha L.; Du, Yiqin

2018-01-01

Abstract Stem cells from human corneal stroma (CSSC) suppress corneal stromal scarring in a mouse wound‐healing model and promote regeneration of native transparent tissue (PMID:25504883). This study investigated efficacy of compressed collagen gel (CCG) as a vehicle to deliver CSSC for corneal therapy. CSSC isolated from limbal stroma of human donor corneas were embedded in soluble rat‐tendon collagen, gelled at 37°C, and partially dehydrated to a thickness of 100 µm by passive absorption. The CCG disks were dimensionally stable, easy to handle, and could be adhered securely to de‐epithelialized mouse cornea with fibrin‐based adhesive. CSSC in CCG maintained >80% viability for >1 week in culture media and could be cryopreserved in 20% fetal bovine serum‐10%DMSO in liquid nitrogen. CCG containing as few as 500 CSSC effectively prevented visible scarring and suppressed expression of fibrotic Col3a1 mRNA. CSSC in CCG were more effective at blocking scarring on a per‐cell basis than CSSC delivered directly in a fibrin gel as previously described. Collagen‐embedded cells retained the ability to suppress corneal scarring after conventional cryopreservation. This study demonstrates use of a common biomaterial that can facilitate storage and handling of stem cells in a manner that may provide off‐the‐shelf delivery of stem cells as a therapy for corneal scarring. stem cells translational medicine 2018;7:487–494 PMID:29654654

Reconstituted human corneal epithelium: a new alternative to the Draize eye test for the assessment of the eye irritation potential of chemicals and cosmetic products.

PubMed

Doucet, O; Lanvin, M; Thillou, C; Linossier, C; Pupat, C; Merlin, B; Zastrow, L

2006-06-01

The aim of this study was to evaluate the interest of a new three-dimensional epithelial model cultivated from human corneal cells to replace animal testing in the assessment of eye tolerance. To this end, 65 formulated cosmetic products and 36 chemicals were tested by means of this in vitro model using a simplified toxicokinetic approach. The chemicals were selected from the ECETOC data bank and the EC/HO International validation study list. Very satisfactory results were obtained in terms of concordance with the Draize test data for the formulated cosmetic products. Moreover, the response of the corneal model appeared predictive of human ocular response clinically observed by ophthalmologists. The in vitro scores for the chemicals tested strongly correlated with their respective scores in vivo. For all the compounds tested, the response of the corneal model to irritants was similar regardless of their chemical structure, suggesting a good robustness of the prediction model proposed. We concluded that this new three-dimensional epithelial model, developed from human corneal cells, could be promising for the prediction of eye irritation induced by chemicals and complex formulated products, and that these two types of materials should be tested using a similar protocol. A simple shortening of the exposure period was required for the chemicals assumed to be more aggressively irritant to the epithelial tissues than the cosmetic formulae.

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

The effect of riboflavin-UV-A treatment on corneal limbal epithelial cells--a study on human cadaver eyes.

PubMed

Vimalin, Jeyalatha; Gupta, Nidhi; Jambulingam, Malathi; Padmanabhan, Prema; Madhavan, Hajib N

2012-09-01

To determine the effect of riboflavin-UV-A treatment on the corneal limbal epithelial cells during a corneal collagen cross-linking (CXL) procedure. Thirty freshly enucleated human cadaveric eyeballs were subjected to a CXL procedure, mimicking the clinical protocol. During the UV-A exposure, one half of the limbus (sector A) was left unprotected, whereas the other half (sector B) was covered by a metal shield. Limbal biopsies from both sectors before and after the procedure were analyzed. Each strip of tissue was divided into 3 segments, for cell count of viable cells, for cultivation on human amniotic membrane (HAM), and for stem cell and differentiated corneal epithelial cell marker studies using reverse transcriptase-polymerase chain reaction. Compared with the cell count before CXL, there was a statistically significant drop in the mean number of viable cells after CXL in sector A but not in sector B. Biopsies from both sectors before CXL and from sector B after CXL showed good growth on HAM. Biopsies from sector A after CXL showed no growth on HAM. The putative stem cell marker ABCG2 was absent in all samples and p63 was absent in 3 of 10 samples taken from sector A after CXL. All markers were present in all samples from sector B after CXL. Riboflavin-UV-A treatment can result in damage to limbal epithelial cells, particularly the stem cells. Covering the limbal region with a metal shield effectively prevents this damage.

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.

Protocol for vital dye staining of corneal endothelial cells.

PubMed

Park, Sunju; Fong, Alan G; Cho, Hyung; Zhang, Cheng; Gritz, David C; Mian, Gibran; Herzlich, Alexandra A; Gore, Patrick; Morganti, Ashley; Chuck, Roy S

2012-12-01

To describe a step-by-step methodology to establish a reproducible staining protocol for the evaluation of human corneal endothelial cells. Four procedures were performed to determine the best protocol. (1) To determine the optimal trypan blue staining method, goat corneas were stained with 4 dilutions of trypan blue (0.4%, 0.2%, 0.1%, and 0.05%) and 1% alizarin red. (2) To determine the optimal alizarin red staining method, goat corneas were stained with 2 dilutions of alizarin red (1% and 0.5%) and 0.2% trypan blue. (3) To ensure that trypan blue truly stains damaged cells, goat corneas were exposed to either 3% hydrogen peroxide or to balanced salt solution, and then stained with 0.2% trypan blue and 0.5% alizarin red. (4) Finally, fresh human corneal buttons were examined; 1 group was stained with 0.2% trypan blue and another group with 0.4% trypan blue. For the 4 procedures performed, the results are as follows: (1) trypan blue staining was not observed in any of the normal corneal samples; (2) 0.5% alizarin red demonstrated sharper cell borders than 1% alizarin red; (3) positive trypan blue staining was observed in the hydrogen peroxide exposed tissue in damaged areas; (4) 0.4% trypan blue showed more distinct positive staining than 0.2% trypan blue. We were able to determine the optimal vital dye staining conditions for human corneal endothelial cells using 0.4% trypan blue and 0.5% alizarin red.

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.

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

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

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.

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.

Generation and characterisation of decellularised human corneal limbus.

PubMed

Spaniol, Kristina; Witt, Joana; Mertsch, Sonja; Borrelli, Maria; Geerling, Gerd; Schrader, Stefan

2018-03-01

Limbal epithelial stem cells (LESC) reside in a niche in the corneo-scleral transition zone. Deficiency leads to pain, corneal opacity, and eventually blindness. LESC transplantation of ex-vivo expanded human LESC on a carrier such as human amniotic membrane is a current treatment option. We evaluated decellularised human limbus (DHL) as a potential carrier matrix for the transplantation of LESC. Human corneas were obtained from the local eye bank. The limbal tissue was decellularised by sodium desoxychelate and DNase solution and sterilised by γ-irradiation. Native limbus- and DHL-surface structures were assessed by scanning electron microscopy and collagen ultrastructure using transmission electron microscopy. Presence and preservation of limbal basement membrane proteins in native limbus and DHL were analysed immunohistochemically. Absence of DNA after decellularisation was assessed by Feulgen staining and DNA quantification. Presence of immune cells was explored by CD45 staining, and potential cytotoxicity was tested using a cell viability assay. In the DHL, the DNA content was reduced from 1.5 ± 0.3 μg/mg to 0.15 ± 0.01 μg/mg; the three-dimensional structure and the arrangement of the collagen fibrils were preserved. Main basement membrane proteins such as collagen IV, laminin, and fibronectin were still present after decellularisation and γ-irradiation. CD45-expressing cells were evident neither in the native limbus nor in the DHL. DHL did not convey cytotoxicity. The extracellular matrix (ECM) of the limbus provides a tissue specific morphology and three-dimensionality consisting of particular ECM proteins. It therefore represents a substantial component of the stem cell niche. The DHL provides a specific limbal niche surrounding, and might serve as an easily producible carrier matrix for LESC transplantation.

Corneal toxicity induced by vesicating agents and effective treatment options

PubMed Central

Goswami, Dinesh G.; Tewari-Singh, Neera; Agarwal, Rajesh

2016-01-01

The vesicating agents sulfur mustard (SM) and lewisite (LEW) are potent chemical warfare agents that primarily cause damage to the ocular, skin, and respiratory systems. However, ocular tissue is the most sensitive organ, and vesicant exposure results in a biphasic injury response, including photophobia, corneal lesions, corneal edema, ulceration, and neovascularization, and may cause loss of vision. There are several reports on ocular injury from exposure to SM, which has been frequently used in warfare. However, there are very few reports on ocular injury by LEW, which indicate that injury symptoms appear instantly after exposure and faster than SM. In spite of extensive research efforts, effective therapies for vesicant-induced ocular injuries, mainly to the most affected corneal tissue, are not available. Hence, we have established primary human corneal epithelial (HCE) cells and rabbit corneal organ culture models with the SM analog nitrogen mustard (NM), which have helped to test the efficacy of potential therapeutic agents. These agents will then be further evaluated against in vivo SM- and LEW-induced corneal injury models, which will assist in the development of potential broad-spectrum therapies against vesicant-induced ocular injuries. PMID:27327041

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.

The Effect of Corneal Epithelium on Corneal Curvature in Patients with Keratoconus.

PubMed

Akcay, Emine Kalkan; Uysal, Betul Seher; Sarac, Ozge; Ugurlu, Nagehan; Yulek, Fatma; Cagil, Nurullah; Aslan, Nabi

2015-01-01

To investigate the effects of corneal epithelium on corneal curvature in patients with keratoconus. This is a prospective, nonrandomized study. Fifty-nine eyes of 47 patients diagnosed as keratoconus and for whom corneal collagen crosslinking (CXL) was recruited in this study. This study is a single-center clinical trial. Pregnancy, lactation, connective tissue disease, corneal thickness below 350 μm, severe dry eyes, or scar of corneal surgery were exclusion criteria. Before and during CXL procedure after removing the corneal epithelium, maximum values of corneal apical curvature, simulated keratometry 1 (Sim-K1), simulated keratometry 2 (Sim-K2), temporal and inferior curvature values, all of which are 1.5 mm from the corneal center, were calculated. These values before and after removal of epithelium were compared statistically. Mean age of patients was 23.30 ± 5.5 (12-38) years. Twenty-eight (59%) were male while 19 (41%) were female. Mean values measured before and after removing the corneal epithelium were: apical curvature; 59.19 ± 7.2 (47.06-82.40) diopter (D) and 61.70 ± 8.8 (49.19-92.66) D (p = 0.001), SimK1; 47.57 ± 4.3 (39.14-64.57) D and 48.23 ± 4.3 (41.89-66.70) D (p = 0.001), SimK2; 52.04 ± 5.3 (43.56-69.34) D and 53.34 ± 5.6 (43.73-70.89) D (p = 0.001), inferior curvature; 53,85 ± 5.2 (43.47-76.56) D and 55.05 ± 5.8 (44.56-81.93) D (p = 0.002), temporal curvature 49.49 ± 5.1 (41.50-71.03) D and 51.53 ± 5.4 (41.58-73.34) D (p = 0.001), respectively. In keratoconus patients during CXL treatment, after removing the corneal epithelium, more steepness is detected in the curvature of the steeper area of the cornea. When evaluating patients with keratoconus, the masking effect of corneal epithelium on values of curvature should be taken into consideration.

Clonidine Induces Apoptosis of Human Corneal Epithelial Cells through Death Receptors-Mediated, Mitochondria-Dependent Signaling Pathway.

PubMed

Fan, Dan; Fan, Ting-Jun

2017-03-01

Clonidine, an α2-adrenoreceptor agonist, is an anti-glaucoma drug clinically used in many developing countries, and its abuse might damage the cornea and impair human vision. However, its cytotoxicity and precise mechanisms need to be elucidated. Herein, we investigated the cytotoxicity of clonidine and its underlying mechanisms, using an in vitro model of human corneal epithelial (HCEP) cells and an in vivo model of cat corneas, respectively. HCEP cells were treated with various doses of clonidine for 1-28 h, resulting in abnormal morphology, decline of cell viability and G1 phase arrest in a time- and/or dose-dependent manner. Moreover, clonidine treatment induced elevation of plasma membrane permeability, phosphatidylserine externalization, DNA fragmentation, and apoptotic body formation in HCEP cells. Furthermore, we found that clonidine treatment resulted in activated caspase-2, -3, -8, and -9, disruption of the mitochondrial transmembrane potential, downregulation of Bcl-2, and upregulation of Bad, cytoplasmic cytochrome c and apoptosis inducing factor, suggesting that clonidine-induced apoptosis is triggered through Fas/TNFR1 death receptors and Bcl-2 family proteins-mediated mitochondria-dependent pathways. Finally, our in vivo results displayed that 0.25% clonidine could induce DNA fragmentation of cat corneal epithelial cells. In summary, our findings suggest that clonidine above 1/32 of its clinical therapeutic dosage is cytotoxic to corneal epithelial cells by inducing cell apoptosis both in vitro and in vivo, and its pro-apoptotic effect on HCEP cells is triggered by a Fas/TNFR1 death receptors-mediated, mitochondria-dependent signaling pathway. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Constitutive and UV-B modulated transcription of Nod-like receptors and their functional partners in human corneal epithelial cells.

PubMed

Benko, Szilvia; Tozser, Jozsef; Miklossy, Gabriella; Varga, Aliz; Kadas, Janos; Csutak, Adrienne; Berta, Andras; Rajnavolgyi, Eva

2008-08-29

To determine the transcription pattern of Nod-like receptors (NLRs) and inflammasome components (apoptosis-associated speck-like protein containing a CARD [ASC], CARD inhibitor of NFkB-activating ligands [Cardinal], and caspase-1) in human corneal epithelial cells obtained from healthy individuals undergoing photorefractive keratectomy and in immortalized human corneal epithelial cells (HCE-T). Human corneal epithelial cells were taken from the eyes of healthy individuals by epithelial ablation for photorefractive keratectomy (PRK). The SV-40 immortalized human corneal epithelial cell line (HCE-T) was cultured. mRNA obtained from the cells was reverse transcribed and subjected to quantitative real-time polymerase chain reaction (PCR) measurements. Protein obtained from HCE-T cells was studied using the western blot technique. HCE-T cells were irradiated by UV-B light or treated with ultrapure peptidoglycan, and the effects were studied at the mRNA and protein level while the supernatant of the cells was tested for the presence of various cytokines by using enzyme-linked immunosorbent assay (ELISA) methods. mRNA levels of the studied proteins in the primary cells of the donors were similar in most cases. The transcription of Nod1, Nod2, NLRX1, Nalp1, and Cardinal was similar in the two cell types. While the expression of Nalp3 and Nalp10 was higher in HCE-T cells, ASC and caspase-1 showed higher transcription levels in the primary cells. NLRC5 and Nalp7 were hardly detectable in the studied cells. Functionality of the Nod1/Nod2 system was demonstrated by increased phosphorylation of IkB upon Nod1/Nod2 agonist ultrapure peptidoglycan treatment in HCE-T cells. While UV-B irradiation exerted a downregulation of both Nalp and Nod mRNAs as well as those of inflammasome components in HCE-T cells, longer incubation of the cells after exposure resulted in recovery or upregulation only of the Nalp sensors. At the protein level, we detected a short isoform of Nalp1 and its

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.

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.

Human corneal epithelial cell shedding and fluorescein staining in response to silicone hydrogel lenses and contact lens disinfecting solutions.

PubMed

Gorbet, Maud; Peterson, Rachael; McCanna, David; Woods, Craig; Jones, Lyndon; Fonn, Desmond

2014-03-01

A pilot study was conducted to evaluate human corneal epithelial cell shedding in response to wearing a silicone hydrogel contact lens/solution combination inducing corneal staining. The nature of ex vivo collected cells staining with fluorescein was also examined. A contralateral eye study was conducted in which up to eight participants were unilaterally exposed to a multipurpose contact lens solution/silicone hydrogel lens combination previously shown to induce corneal staining (renu® fresh™ and balafilcon A; test eye), with the other eye using a combination of balafilcon A soaked in a hydrogen peroxide care system (Clear Care®; control eye). Lenses were worn for 2, 4 or 6 hours. Corneal staining was graded after lens removal. The Ocular Surface Cell Collection Apparatus was used to collect cells from the cornea and the contact lens. In the test eye, maximum solution-induced corneal staining (SICS) was observed after 2 hours of lens wear (reducing significantly by 4 hours; p < 0.001). There were significantly more cells collected from the test eye after 4 hours of lens wear when compared to the control eye and the collection from the test eye after 2 hours (for both; n = 5; p < 0.001). The total cell yield at 4 hours was 813 ± 333 and 455 ± 218 for the test and control eyes, respectively (N = 5, triplicate, p = 0.003). A number of cells were observed to have taken up the fluorescein dye from the initial fluorescein instillation. Confocal microscopy of fluorescein-stained cells revealed that fluorescein was present throughout the cell cytoplasm and was retained in the cells for many hours after recovery from the corneal surface. This pilot study indicates that increased epithelial cell shedding was associated with a lens-solution combination which induces SICS. Our data provides insight into the transient nature of the SICS reaction and the nature of fluorescein staining observed in SICS.

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.

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.

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.

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.

Corneal electrolysis for recurrence of corneal stromal dystrophy after keratoplasty

PubMed Central

Mashima, Y; Kawai, M; Yamada, M

2002-01-01

Aims: To evaluate corneal electrolysis as a treatment for recurrent diffuse corneal opacities at the host-graft interface of the stroma or at the subepithelial region in two types of granular corneal dystrophy (GCD). Methods: Recurrence developed at the host-graft interface of the stroma after lamellar keratoplasty in a patient with Avellino corneal dystrophy (ACD). At surgery, the deep aspect of the graft in this patient was partially separated from host tissue to expose the deposits, with one third of the host-graft junction left intact. The graft was everted, and electrolysis was applied directly to remove the deposits attached to both surfaces of the host and the graft. Then the graft was returned to its place and sutured. In two patients with homozygous ACD and one patient with the superficial variant of GCD, diffuse subepithelial opacities developed following penetrating keratoplasty. Electrolysis was applied directly to the corneal surface. Results: Deposits at the host-graft interface of the stroma and in the subepithelial region disappeared following treatment, and vision recovered in all patients. Conclusions: This method is a simple, easy, and inexpensive way to remove deposits that recur after lamellar or penetrating keratoplasty. PMID:11864880

Corneal electrolysis for recurrence of corneal stromal dystrophy after keratoplasty.

PubMed

Mashima, Y; Kawai, M; Yamada, M

2002-03-01

To evaluate corneal electrolysis as a treatment for recurrent diffuse corneal opacities at the host-graft interface of the stroma or at the subepithelial region in two types of granular corneal dystrophy (GCD). Recurrence developed at the host-graft interface of the stroma after lamellar keratoplasty in a patient with Avellino corneal dystrophy (ACD). At surgery, the deep aspect of the graft in this patient was partially separated from host tissue to expose the deposits, with one third of the host-graft junction left intact. The graft was everted, and electrolysis was applied directly to remove the deposits attached to both surfaces of the host and the graft. Then the graft was returned to its place and sutured. In two patients with homozygous ACD and one patient with the superficial variant of GCD, diffuse subepithelial opacities developed following penetrating keratoplasty. Electrolysis was applied directly to the corneal surface. Deposits at the host-graft interface of the stroma and in the subepithelial region disappeared following treatment, and vision recovered in all patients. This method is a simple, easy, and inexpensive way to remove deposits that recur after lamellar or penetrating keratoplasty.

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.

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.

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

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.

Glucocorticoid action in human corneal epithelial cells establishes roles for corticosteroids in wound healing and barrier function of the eye.

PubMed

Kadmiel, Mahita; Janoshazi, Agnes; Xu, Xiaojiang; Cidlowski, John A

2016-11-01

Glucocorticoids play diverse roles in almost all physiological systems of the body, including both anti-inflammatory and immunosuppressive roles. Synthetic glucocorticoids are one of the most widely prescribed drugs and are used in the treatment of conditions such as autoimmune diseases, allergies, ocular disorders and certain types of cancers. In the interest of investigating glucocorticoid actions in the cornea of the eye, we established that multiple cell types in mouse corneas express functional glucocorticoid receptor (GR) with corneal epithelial cells having robust expression. To define glucocorticoid actions in a cell type-specific manner, we employed immortalized human corneal epithelial (HCE) cell line to define the glucocorticoid transcriptome and elucidated its functions in corneal epithelial cells. Over 4000 genes were significantly regulated within 6 h of dexamethasone treatment, and genes associated with cell movement, cytoskeletal remodeling and permeability were highly regulated. Real-time in vitro wound healing assays revealed that glucocorticoids delay wound healing by attenuating cell migration. These functional alterations were associated with cytoskeletal remodeling at the wounded edge of a scratch-wounded monolayer. However, glucocorticoid treatment improved the organization of tight-junction proteins and enhanced the epithelial barrier function. Our results demonstrate that glucocorticoids profoundly alter corneal epithelial gene expression and many of these changes likely impact both wound healing and epithelial cell barrier function. Published by Elsevier Ltd.

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.

Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization.

PubMed

Lee, Jung Eun; Kim, Koung Li; Kim, Danbi; Yeo, Yeongju; Han, Hyounkoo; Kim, Myung Goo; Kim, Sun Hwa; Kim, Hyuncheol; Jeong, Ji Hoon; Suh, Wonhee

2017-01-01

Pathological angiogenesis is one of the major symptoms of severe ocular diseases, including corneal neovascularization. The blockade of vascular endothelial growth factor (VEGF) action has been recognized as an efficient strategy for treating corneal neovascularization. In this study, we aimed to investigate whether nanoparticle-based delivery of apatinib, a novel and selective inhibitor of VEGF receptor 2, inhibits VEGF-mediated angiogenesis and suppresses experimental corneal neovascularization. Water-insoluble apatinib was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro angiogenesis assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles potently inhibited VEGF-induced tube formation, scratch wounding migration, and proliferation of human endothelial cells. In a rat model of alkali burn injury-induced corneal neovascularization, a subconjunctival injection of Apa-HSA-PEG nanoparticles induced a significant decrease in neovascularization compared to that observed with an injection of free apatinib solution or phosphate-buffered saline. An in vivo distribution study using HSA-PEG nanoparticles loaded with fluorescent hydrophobic model drugs revealed the presence of a substantial number of nanoparticles in the corneal stroma within 24 h after injection. These in vitro and in vivo results demonstrate that apatinib-loaded nanoparticles may be promising for the prevention and treatment of corneal neovascularization-related ocular disorders.

Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization

PubMed Central

Lee, Jung Eun; Kim, Koung Li; Kim, Danbi; Yeo, Yeongju; Han, Hyounkoo; Kim, Myung Goo; Kim, Sun Hwa; Kim, Hyuncheol; Jeong, Ji Hoon; Suh, Wonhee

2017-01-01

Pathological angiogenesis is one of the major symptoms of severe ocular diseases, including corneal neovascularization. The blockade of vascular endothelial growth factor (VEGF) action has been recognized as an efficient strategy for treating corneal neovascularization. In this study, we aimed to investigate whether nanoparticle-based delivery of apatinib, a novel and selective inhibitor of VEGF receptor 2, inhibits VEGF-mediated angiogenesis and suppresses experimental corneal neovascularization. Water-insoluble apatinib was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro angiogenesis assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles potently inhibited VEGF-induced tube formation, scratch wounding migration, and proliferation of human endothelial cells. In a rat model of alkali burn injury-induced corneal neovascularization, a subconjunctival injection of Apa-HSA-PEG nanoparticles induced a significant decrease in neovascularization compared to that observed with an injection of free apatinib solution or phosphate-buffered saline. An in vivo distribution study using HSA-PEG nanoparticles loaded with fluorescent hydrophobic model drugs revealed the presence of a substantial number of nanoparticles in the corneal stroma within 24 h after injection. These in vitro and in vivo results demonstrate that apatinib-loaded nanoparticles may be promising for the prevention and treatment of corneal neovascularization-related ocular disorders. PMID:28740387

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.

Corneal tissue welding with infrared laser irradiation after clear corneal incision.

PubMed

Rasier, Rfat; Ozeren, Mediha; Artunay, Ozgür; Bahçecioğlu, Halil; Seçkin, Ismail; Kalaycoğlu, Hamit; Kurt, Adnan; Sennaroğlu, Alphan; Gülsoy, Murat

2010-09-01

The aim of this study was to investigate the potential of infrared lasers for corneal welding to seal corneal cuts done in an experimental animal model. Full-thickness corneal cuts on freshly enucleated bovine eyes were irradiated with infrared (809-nm diode, 980-nm diode, 1070-nm YLF, and 1980-nm Tm:YAP) lasers to get immediate laser welding. An 809-nm laser was used with the topical application of indocyanine green to enhance the photothermal interaction at the weld site. In total, 60 bovine eyes were used in this study; 40 eyes were used in the first part of the study for the determination of optimal welding parameters (15 eyes were excluded because of macroscopic carbonization, opacification, or corneal shrinkage; 2 eyes were used for control), and 20 eyes were used for further investigation of more promising lasers (YLF and Tm:YAP). Laser wavelength, irradiating power, exposure time, and spot size were the dose parameters, and optimal dose for immediate closure with minimal thermal damage was estimated through histological examination of welded samples. In the first part of the study, results showed that none of the applications was satisfactory. Full-thickness success rates were 28% (2 of 7) for 809-nm and for 980-nm diode lasers and 67% (2 of 3) for 1070-nm YLF and (4 of 6) for 1980-nm Tm:YAP lasers. In the second part of the study, YLF and Tm:YAP lasers were investigated with bigger sample size. Results were not conclusive but promising again. Five corneal incisions were full-thickness welded out of 10 corneas with 1070-nm laser, and 4 corneal incisions were partially welded out of 10 corneas with 1980-nm laser in the second part of the study. Results showed that noteworthy corneal welding could be obtained with 1070-nm YLF laser and 1980-nm Tm:YAP laser wavelengths. Furthermore, in vitro and in vivo studies will shed light on the potential usage of corneal laser welding technique.

Changes in rabbit corneal innervation induced by the topical application of benzalkonium chloride.

PubMed

Chen, Wensheng; Zhang, Zhenhao; Hu, Jiaoyue; Xie, Hui; Pan, Juxin; Dong, Nuo; Liu, Zuguo

2013-12-01

To investigate the effect of benzalkonium chloride (BAK) on corneal nerves. Fifty-four adult New Zealand Albino rabbits were randomly divided into 3 groups. BAK at concentrations of 0.005%, 0.01%, or 0.02% was applied once daily to 1 eye of each rabbit for 9 days. The contralateral untreated eyes were used as controls. Corneal mechanical sensitivity, aqueous tear production, tear break-up time (BUT), fluorescein, and Rose Bengal staining scores were compared with those of control values on days 3, 6, and 9. Corneal whole mounts were immunostained with a specific antitubulin βIII antibody to label nerve fibers. Epithelial superficial nerve terminal, subbasal, and stromal nerve fiber densities were quantified. The structure of the central cornea was examined by means of in vivo confocal microscopy on day 9. The topical application of BAK resulted in lower corneal sensitivity and higher Rose Bengal staining scores on day 3, whereas there were no significant changes in the BUT, Schirmer, and corneal fluorescein scores. Decreased nerve densities in superficial and subbasal layers were observed in BAK-treated eyes on days 3 and 6, respectively. The eyes treated with 0.02% BAK exhibited significantly reduced Schirmer scores, BUT, and stromal nerve fiber density, and increased fluorescein staining scores on day 9. Corneal superficial epithelial cell size was significantly larger in all BAK-treated eyes compared with that in control eyes. The topical application of BAK can quickly cause corneal hypoesthesia without tear deficiency. Changes in corneal innervation significantly correlate with BAK-induced ocular surface changes.

21 CFR 886.1220 - Corneal electrode.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Corneal electrode. 886.1220 Section 886.1220 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... to the cornea to provide data showing the changes in electrical potential in the retina after...

A fully-automatic fast segmentation of the sub-basal layer nerves in corneal images.

PubMed

Guimarães, Pedro; Wigdahl, Jeff; Poletti, Enea; Ruggeri, Alfredo

2014-01-01

Corneal nerves changes have been linked to damage caused by surgical interventions or prolonged contact lens wear. Furthermore nerve tortuosity has been shown to correlate with the severity of diabetic neuropathy. For these reasons there has been an increasing interest on the analysis of these structures. In this work we propose a novel, robust, and fast fully automatic algorithm capable of tracing the sub-basal plexus nerves from human corneal confocal images. We resort to logGabor filters and support vector machines to trace the corneal nerves. The proposed algorithm traced most of the corneal nerves correctly (sensitivity of 0.88 ± 0.06 and false discovery rate of 0.08 ± 0.06). The displayed performance is comparable to a human grader. We believe that the achieved processing time (0.661 ± 0.07 s) and tracing quality are major advantages for the daily clinical practice.

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 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.

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.

Mutations in LOXHD1, a Recessive-Deafness Locus, Cause Dominant Late-Onset Fuchs Corneal Dystrophy

PubMed Central

Riazuddin, S. Amer; Parker, David S.; McGlumphy, Elyse J.; Oh, Edwin C.; Iliff, Benjamin W.; Schmedt, Thore; Jurkunas, Ula; Schleif, Robert; Katsanis, Nicholas; Gottsch, John D.

2012-01-01

Fuchs corneal dystrophy (FCD) is a genetic disorder of the corneal endothelium and is the most common cause of corneal transplantation in the United States. Previously, we mapped a late-onset FCD locus, FCD2, on chromosome 18q. Here, we present next-generation sequencing of all coding exons in the FCD2 critical interval in a multigenerational pedigree in which FCD segregates as an autosomal-dominant trait. We identified a missense change in LOXHD1, a gene causing progressive hearing loss in humans, as the sole variant capable of explaining the phenotype in this pedigree. We observed LOXHD1 mRNA in cultured human corneal endothelial cells, whereas antibody staining of both human and mouse corneas showed staining in the corneal epithelium and endothelium. Corneal sections of the original proband were stained for LOXHD1 and demonstrated a distinct increase in antibody punctate staining in the endothelium and Descemet membrane; punctate staining was absent from both normal corneas and FCD corneas negative for causal LOXHD1 mutations. Subsequent interrogation of a cohort of >200 sporadic affected individuals identified another 15 heterozygous missense mutations that were absent from >800 control chromosomes. Furthermore, in silico analyses predicted that these mutations reside on the surface of the protein and are likely to affect the protein's interface and protein-protein interactions. Finally, expression of the familial LOXHD1 mutant allele as well as two sporadic mutations in cells revealed prominent cytoplasmic aggregates reminiscent of the corneal phenotype. All together, our data implicate rare alleles in LOXHD1 in the pathogenesis of FCD and highlight how different mutations in the same locus can potentially produce diverse phenotypes. PMID:22341973

Oxygen-deficient metabolism and corneal edema

PubMed Central

Leung, B.K.; Bonanno, J.A.; Radke, C.J.

2014-01-01

Wear of low-oxygen-transmissible soft contact lenses swells the cornea significantly, even during open eye. Although oxygen-deficient corneal edema is well-documented, a self-consistent quantitative prediction based on the underlying metabolic reactions is not available. We present a biochemical description of the human cornea that quantifies hypoxic swelling through the coupled transport of water, salt, and respiratory metabolites. Aerobic and anaerobic consumption of glucose, as well as acidosis and pH buffering, are incorporated in a seven-layer corneal model (anterior chamber, endothelium, stroma, epithelium, postlens tear film, contact lens, and prelens tear film). Corneal swelling is predicted from coupled transport of water, dissolved salts, and especially metabolites, along with membrane-transport resistances at the endothelium and epithelium. At the endothelium, the Na+/K+ - ATPase electrogenic channel actively transports bicarbonate ion from the stroma into the anterior chamber. As captured by the Kedem–Katchalsky membrane-transport formalism, the active bicarbonate-ion flux provides the driving force for corneal fluid pump-out needed to match the leak-in tendency of the stroma. Increased lactate-ion production during hypoxia osmotically lowers the pump-out rate requiring the stroma to swell to higher water content. Concentration profiles are predicted for glucose, water, oxygen, carbon dioxide, and hydronium, lactate, bicarbonate, sodium, and chloride ions, along with electrostatic potential and pressure profiles. Although the active bicarbonate-ion pump at the endothelium drives bicarbonate into the aqueous humor, we find a net flux of bicarbonate ion into the cornea that safeguards against acidosis. For the first time, we predict corneal swelling upon soft-contact-lens wear from fundamental biophysico-chemical principles. We also successfully predict that hypertonic tear alleviates contact-lens-induced edema. PMID:21820076

Oxygen-deficient metabolism and corneal edema.

PubMed

Leung, B K; Bonanno, J A; Radke, C J

2011-11-01

Wear of low-oxygen-transmissible soft contact lenses swells the cornea significantly, even during open eye. Although oxygen-deficient corneal edema is well-documented, a self-consistent quantitative prediction based on the underlying metabolic reactions is not available. We present a biochemical description of the human cornea that quantifies hypoxic swelling through the coupled transport of water, salt, and respiratory metabolites. Aerobic and anaerobic consumption of glucose, as well as acidosis and pH buffering, are incorporated in a seven-layer corneal model (anterior chamber, endothelium, stroma, epithelium, postlens tear film, contact lens, and prelens tear film). Corneal swelling is predicted from coupled transport of water, dissolved salts, and especially metabolites, along with membrane-transport resistances at the endothelium and epithelium. At the endothelium, the Na+/K+ - ATPase electrogenic channel actively transports bicarbonate ion from the stroma into the anterior chamber. As captured by the Kedem-Katchalsky membrane-transport formalism, the active bicarbonate-ion flux provides the driving force for corneal fluid pump-out needed to match the leak-in tendency of the stroma. Increased lactate-ion production during hypoxia osmotically lowers the pump-out rate requiring the stroma to swell to higher water content. Concentration profiles are predicted for glucose, water, oxygen, carbon dioxide, and hydronium, lactate, bicarbonate, sodium, and chloride ions, along with electrostatic potential and pressure profiles. Although the active bicarbonate-ion pump at the endothelium drives bicarbonate into the aqueous humor, we find a net flux of bicarbonate ion into the cornea that safeguards against acidosis. For the first time, we predict corneal swelling upon soft-contact-lens wear from fundamental biophysico-chemical principles. We also successfully predict that hypertonic tear alleviates contact-lens-induced edema. Copyright © 2011 Elsevier Ltd. All rights

Drug-induced corneal damage.

PubMed

2014-04-01

Corneal damage can have a variety of causes, including infections, chemical splashes, environmental factors (radiation, trauma, contact lenses, etc.), and systemic diseases (genetic, autoimmune, inflammatory, metabolic, etc.). A wide range of drugs can also damage the cornea. The severity of drug-induced corneal changes can range from simple asymptomatic deposits to irreversible, sight-threatening damage. Several factors can influence the onset of corneal lesions. Some factors, such as the dose, are treatment-related, while others such as contact lenses, are patient-related. A variety of mechanisms may be involved, including corneal dryness, changes in the corneal epithelium, impaired wound healing and deposits. Many drugs can damage the cornea through direct contact, after intraocular injection or instillation, including VEGF inhibitors, anti-inflammatory drugs, local anaesthetics, glaucoma drugs, fluoroquinolones, and preservatives. Some systemically administered drugs can also damage the cornea, notably cancer drugs, amiodarone and isotretinoin. Vulnerable patients should be informed of this risk if they are prescribed a drug with the potential to damage the cornea so that they can identify problems in a timely manner. It may be necessary to discontinue the suspect drug when signs and symptoms of corneal damage occur.

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

Mechanism of induction of fibroblast to corneal endothelial cell.

PubMed

Jiang, Yan; Fu, Wei-Cai; Zhang, Lin

2014-08-01

To explore mechanism of nduction of fibroblast to corneal endothelial cell. Rabbit conjunctiva fibroblasts were used as feeder cells, rabbit oral mucosa epithelial cells were used as seed cells, and human denuded amniotic membrane was used as carrier to establish tissue engineering corneal endothelium. The transformation effect was observed. As concentration of mitomycin C increased, cell survival rate gradually decreased, cell proliferation was obviously inhibited when concentration≥25 μg/mL; 5 days after being treated by 5 μg/mL mitomycin C, cell body was enlarged and extended without cell fusion, however after being treated by 0.5 μg/mL mitomycin C, cell body was significantly proliferated and gradually fused; after 3 weeks of culture, stratified epithelium appeared on rabbit oral mucosa epithelial cells, differentiation layers were 4-5 and were well differentiated, the morphology was similar to corneal endothelial cells; Under electron microscope, surface layer of cells were polygonal, tightly connected to another with microvilli on the border, there was hemidesmosome between basal cells and human denuded amniotic membrane. Fibroblast cells have the potential of multi-directional differentiation, effective induction can promote emergence of intercellular desmosomes between seed cells and emergence of epithelial surface microvilli, and differentiate to the corneal endothelial cell. However, clinical application still needs more research and safety evaluation. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

A hyaluronan hydrogel scaffold-based xeno-free culture system for ex vivo expansion of human corneal epithelial stem cells.

PubMed

Chen, D; Qu, Y; Hua, X; Zhang, L; Liu, Z; Pflugfelder, S C; Li, D-Q

2017-06-01

PurposeTo develop a hyaluronan hydrogel scaffold-based xeno-free culture system for ex vivo cultivation of human corneal epithelial stem cells (CESCs).Patients and MethodsCESCs were cultivated from donor limbal explants on the HyStem-C Hydrogel bio-scaffold in 12-well plates for 3 weeks. Group A used the traditional supplemented hormonal epidermal medium (SHEM) and group B used the defined SHEM (without fetal bovine serum and toxin A, adding 20% serum replacement). The growth and morphology of the cultured cells were assessed by phase contrast microscope. The expressions of specific cell markers were assessed by immunofluorescence staining and quantitative real-time PCR (qRT-PCR).ResultsSuccessful cultures of CESCs were obtained in both groups, resulting in multilayered stratified epithelia. Comparing to group A, the cells in group B was grown slightly slower and formed less cellular layers at the end of culture. The corneal specific cytokeratin (K) 12 and differentiation markers, involucrin, and connexin 43, were mainly expressed in the superficial cellular layers in both groups. Interestingly, certain basal cells were immune-positive to proposed stem cell markers such as K19, ABCG2, and integrin β1 in both groups. There was no significant difference between the two groups with regard to the gene expression levels of all these selected corneal markers (all P>0.05).ConclusionsThe hyaluronan hydrogel scaffold-based xeno-free culture system may support the expansion of regenerative CESCs without the risk of xeno component contamination. The regenerated epithelium maintains similar characteristics of native corneal epithelium.

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.

Rebamipide increases the mucin-like glycoprotein production in corneal epithelial cells.

PubMed

Takeji, Yasuhiro; Urashima, Hiroki; Aoki, Akihiro; Shinohara, Hisashi

2012-06-01

Dry eye is a multifactorial disease of tears and the ocular surface due to tear deficiency or excessive tear evaporation. Tear film instability is due to a disturbance in ocular surface mucin leading to a dysfunction of mucin, resulting in dry eye. In this study, we examined the effect of rebamipide, an anti-ulcer agent, on glycoconjugate production, as an indicator of mucin-like glycoprotein in cultured corneal epithelial cells. Further, we investigated the effect of rebamipide on the gene expression of membrane-associated mucins. Confluent cultured human corneal epithelial cells were incubated with rebamipide for 24 h. The glycoconjugate content in the supernatant and the cell extracts was measured by wheat germ agglutinin-enzyme-linked lectin assay combined gel-filtration method. In the experiment on mucin gene expression, cultured human corneal epithelial cells were collected at 0, 3, 6, and 12 h after administration of rebamipide. Real-time quantitative polymerase chain reaction was used to analyze the quantity of MUC1, MUC 4, and MUC16 gene expression. Rebamipide significantly increased the glycoconjugate contents in the supernatant and cell extract. In the mucin gene expression in the cells, rebamipide increased MUC1 and MUC4 gene expression, but did not increase MUC16 gene expression. Rebamipide promoted glycoconjugate, which has a property as a mucin-like glycoprotein, in human corneal epithelial cells. The increased production was mediated by MUC1 and MUC4 gene expression.

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

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.

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.

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.

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

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.

Mucin characteristics of human corneal-limbal epithelial cells that exclude the rose bengal anionic dye.

PubMed

Argüeso, Pablo; Tisdale, Ann; Spurr-Michaud, Sandra; Sumiyoshi, Mika; Gipson, Ilene K

2006-01-01

Rose bengal is an organic anionic dye used to assess damage of the ocular surface epithelium in ocular surface disease. It has been proposed that mucins have a protective role, preventing rose bengal staining of normal ocular surface epithelial cells. The current study was undertaken to evaluate rose bengal staining in a human corneal-limbal epithelial (HCLE) cell line known to produce and glycosylate membrane-associated mucins. HCLE cells were grown to confluence in serum-free medium and switched to DMEM/F12 with 10% serum to promote differentiation. Immunolocalization of the membrane-associated mucins MUC1 and MUC16 and the T-antigen carbohydrate epitope was performed with the monoclonal antibodies HMFG-2 and OC125 and jacalin lectin, respectively. To assess dye uptake, cultures were incubated for 5 minutes with 0.1% rose bengal and photographed. To determine whether exclusion of negatively charged rose bengal requires a negative charge at the cell surface, cells were incubated with fluoresceinated cationized ferritin. The effect of hyperosmotic stress on rose bengal staining in vitro was evaluated by increasing the ion concentration (Ca+2 and Mg+2) in the rose bengal uptake assay. The cytoplasm and nucleus of confluent HCLE cells cultured in media without serum, lacking the expression of MUC16 but not MUC1, as well as human corneal fibroblasts, which do not express mucins, stained with rose bengal. Culture of HCLE cells in medium containing serum resulted in the formation of islands of stratified cells that excluded rose bengal. Apical cells of the stratified islands produced MUC16 and the T-antigen carbohydrate epitope on their apical surfaces. Colocalization experiments demonstrated that fluoresceinated cationized ferritin did not bind to these stratified cells, indicating that rose bengal is excluded from cells that lack negative charges. Increasing the amounts of divalent cations in the media reduced the cellular area protected against rose bengal uptake

Dynamic Corneal Surface Mapping with Electronic Speckle Pattern Interferometry

NASA Astrophysics Data System (ADS)

Iqbal, S.; Gualini, M. M. S.

2013-06-01

In view of the fast advancement in ophthalmic technology and corneal surgery, there is a strong need for the comprehensive mapping and characterization techniques for corneal surface. Optical methods with precision non-contact approaches have been found to be very useful for such bio measurements. Along with the normal mapping approaches, elasticity of corneal surface has an important role in its characterization and needs to be appropriately measured or estimated for broader diagnostics and better prospective surgical results, as it has important role in the post-op corneal surface reconstruction process. Use of normal corneal topographic devices is insufficient for any intricate analysis since these devices operate at relatively moderate resolution. In the given experiment, Pulsed Electronic Speckle Pattern Interferometry has been utilized along with an excitation mechanism to measure the dynamic response of the sample cornea. A Pulsed ESPI device has been chosen for the study because of its micron-level resolution and other advantages in real-time deformation analysis. A bovine cornea has been used as a sample in the subject experiment. The dynamic response has been taken on a chart recorder and it is observed that it does show a marked deformation at a specific excitation frequency, which may be taken as a characteristic elasticity parameter for the surface of that corneal sample. It was seen that outside resonance conditions the bovine cornea was not that much deformed. Through this study, the resonance frequency and the corresponding corneal deformations are mapped and plotted in real time. In these experiments, data was acquired and processed by FRAMES plus computer analysis system. With some analysis of the results, this technique can help us to refine a more detailed corneal surface mathematical model and some preliminary work was done on this. Such modelling enhancements may be useful for finer ablative surgery planning. After further experimentation

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.

Feeder-free differentiation of cells exhibiting characteristics of corneal endothelium from human induced pluripotent stem cells.

PubMed

Wagoner, Michael D; Bohrer, Laura R; Aldrich, Benjamin T; Greiner, Mark A; Mullins, Robert F; Worthington, Kristan S; Tucker, Budd A; Wiley, Luke A

2018-05-08

The purpose of this study was to devise a strategy for the derivation of corneal endothelial cells (CEnCs) from adult fibroblast-derived induced pluripotent stem cells (iPSCs). IPSCs were generated from an adult human with normal ocular history via expression of OCT4 , SOX2 , KLF4 and c-MYC Neural crest cells (NCCs) were differentiated from iPSCs via addition of CHIR99021 and SB4315542. NCCs were driven toward a CEnC fate via addition of B27, PDGF-BB and DKK-2 to CEnC media. Differentiation of NCCs and CEnCs was evaluated via rt-PCR, morphological and immunocytochemical analysis. At 17 days post-NCC induction, there were notable changes in cell morphology and upregulation of the neural crest lineage transcripts PAX3 , SOX9 , TFAP2A , SOX10 and p75NTR and the proteins p75/NGFR and SOX10. Exposure of NCCs to B27, PDGF-BB and DKK-2 induced a shift in morphology from a spindle-shaped neural phenotype to a tightly-packed hexagonal appearance and increased expression of the transcripts ATP1A1 , COL8A1 , COL8A2 , AQP1 and CDH2 and the proteins ZO-1, N-Cad, AQP-1 and Na + /K + ATPase. Replacement of NCC media with CEnC media on day 3, 5 or 8 reduced the differentiation time needed to yield CEnCs. IPSC-derived CEnCs could be used for evaluation of cornea endothelial disease pathophysiology and for testing of novel therapeutics. © 2018. Published by The Company of Biologists Ltd.

Modeling and minimizing interference from corneal birefringence in retinal birefringence scanning for foveal fixation detection

PubMed Central

Irsch, Kristina; Gramatikov, Boris; Wu, Yi-Kai; Guyton, David

2011-01-01

Utilizing the measured corneal birefringence from a data set of 150 eyes of 75 human subjects, an algorithm and related computer program, based on Müller-Stokes matrix calculus, were developed in MATLAB for assessing the influence of corneal birefringence on retinal birefringence scanning (RBS) and for converging upon an optical/mechanical design using wave plates (“wave-plate-enhanced RBS”) that allows foveal fixation detection essentially independently of corneal birefringence. The RBS computer model, and in particular the optimization algorithm, were verified with experimental human data using an available monocular RBS-based eye fixation monitor. Fixation detection using wave-plate-enhanced RBS is adaptable to less cooperative subjects, including young children at risk for developing amblyopia. PMID:21750772

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.

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.

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

Successful transplantation of in vitro expanded human cadaver corneal endothelial precursor cells on to a cadaver bovine's eye using a nanocomposite gel sheet.

PubMed

Parikumar, Periyasamy; Haraguchi, Kazutoshi; Ohbayashi, Akira; Senthilkumar, Rajappa; Abraham, Samuel J K

2014-05-01

In vitro expansion of human corneal endothelial precursor (HCEP) cells has been reported via production of cell aggregated spheres. However, to translate this procedure in human patients warrants maintaining the position of the eyeballs facing down for 36 h, which is not feasible. In this study, we report a method using a nanocomposite (NC) gel sheet to accomplish the integration of HCEP cells to the endothelium of cadaver bovine's eyes. HCEP cells were isolated from the corneal endothelium of a cadaver human eye and then expanded using a thermoreversible gelation polymer (TGP) as reported earlier. For the study, three cadaver bovine eyes were used. The NC gel sheets were inserted into the bovine eyes', aligned and suture-fixed in position under the host endothelium. HCEP cells previously expanded in the TGP were harvested and injected using a 26-gauge syringe between the endothelium and the NC gel sheet. The eyes were left undisturbed for three hours following which the NC gel sheets were gently removed. The corneas were harvested and subjected to histopathological studies. Histopathological studies showed that all the three corneas used for NC gel sheet implantation showed the presence of engrafted HCEP cells, seen as multi-layered cells over the native endothelium of the bovine cornea. Examination of the NC gel sheets used for implantation showed that only very few corneal endothelial cells remained on the sheets amounting to what could be considered negligible. The use of the NC gel sheet makes HCEP cell transplantation feasible for human patients. Further in vitro basic studies followed by translational studies are necessary to bring this method for clinical application in appropriate indications.

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

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

Investigations of the corneal epithelium in Veterinary Medicine: State of the art on corneal stem cells found in different mammalian species and their putative application.

PubMed

Patruno, M; Perazzi, A; Martinello, T; Gomiero, C; Maccatrozzo, L; Iacopetti, I

2018-05-08

The existence of progenitor cells that can readily differentiate into a specific cell type is a common cellular strategy for physiological tissue growth and repair mechanisms. In the mammalian cornea, many aspects regarding the nature and location of these cells are still unclear. In the human limbus (peripheral area of the cornea) progenitor cells have been found and characterized but in non-human mammals, the picture is not so clear. In this review, we examine current knowledge about the morphology of limbus and the localization of corneal epithelial stem cells in all species studied so far, comparing data with humans. We have also explored different research directions in the veterinary field in order to discuss the: i) currently used protocols and ii) best range of treatments for ocular pathologies in which corneal stem cells are involved. Copyright © 2018. Published by Elsevier Ltd.

Glaucoma after corneal replacement.

PubMed

Baltaziak, Monika; Chew, Hall F; Podbielski, Dominik W; Ahmed, Iqbal Ike K

Glaucoma is a well-known complication after corneal transplantation surgery. Traditional corneal transplantation surgery, specifically penetrating keratoplasty, has been slowly replaced by the advent of new corneal transplantation procedures: primarily lamellar keratoplasties. There has also been an emergence of keratoprosthesis implants for eyes that are high risk of failure with penetrating keratoplasty. Consequently, there are different rates of glaucoma, pathogenesis, and potential treatment in the form of medical, laser, or surgical therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

The risk of microbial keratitis with overnight corneal reshaping lenses.

PubMed

Bullimore, Mark A; Sinnott, Loraine T; Jones-Jordan, Lisa A

2013-09-01

To estimate the incidence of microbial keratitis (MK) associated with overnight corneal reshaping contact lenses and to compare rates in children and adults. A retrospective study of randomly selected practitioners, stratified by order volume and lens company, was conducted. Practitioners were invited to participate and those agreeing were asked to provide deidentified patient information for up to 50 lens orders and to complete a comprehensive event form for any of these patients who have attended an unscheduled visit for a painful red eye. Duration of contact lens wear was calculated from the original fitting date or January 2005 (whichever was later) to when the patient was last seen by the practitioner wearing the lenses on a regular basis. Cases of MK were classified by majority decision of a 5-member expert panel. For the 191 practitioners who could be contacted, 119 (62%) agreed to participate. Subsequently, 11 withdrew, 22 did not respond, and 86 (43%) returned completed forms corresponding to 2202 lens orders and 1494 patients. Limiting the sample to those patients with at least 3 months of documented contact lens wear since 2005 resulted in a sample of 1317 patients; 640 adults (49%) and 677 children (51%) representing 2599 patient-years of wear (adults = 1164; children = 1435). Eight events of corneal infiltrates associated with a painful red eye were reported (six in children and two in adults). Two were classified as MK. Both occurred in children but neither resulted in a loss of visual acuity. The overall estimated incidence of MK is 7.7 per 10,000 years of wear (95% confidence interval [CI] = 0.9 to 27.8). For children, the estimated incidence of MK is 13.9 per 10,000 patient-years (95% CI = 1.7 to 50.4). For adults, the estimated incidence of MK is 0 per 10,000 patient-years (95% CI = 0 to 31.7). The risk of MK with overnight corneal reshaping contact lenses is similar to that with other overnight modalities. The fact that the CIs for the rates

Self-organized centripetal movement of corneal epithelium in the absence of external cues

NASA Astrophysics Data System (ADS)

Lobo, Erwin P.; Delic, Naomi C.; Richardson, Alex; Raviraj, Vanisri; Halliday, Gary M.; di Girolamo, Nick; Myerscough, Mary R.; Lyons, J. Guy

2016-08-01

Maintaining the structure of the cornea is essential for high-quality vision. In adult mammals, corneal epithelial cells emanate from stem cells in the limbus, driven by an unknown mechanism towards the centre of the cornea as cohesive clonal groups. Here we use complementary mathematical and biological models to show that corneal epithelial cells can self-organize into a cohesive, centripetal growth pattern in the absence of external physiological cues. Three conditions are required: a circumferential location of stem cells, a limited number of cell divisions and mobility in response to population pressure. We have used these complementary models to provide explanations for the increased rate of centripetal migration caused by wounding and the potential for stem cell leakage to account for stable transplants derived from central corneal tissue, despite the predominantly limbal location of stem cells.

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.

A Prospective Study of Pterygium Excision and Conjunctival Autograft With Human Fibrin Tissue Adhesive: Effects on Vision, Refraction, and Corneal Topography.

PubMed

Misra, Stuti; Craig, Jennifer P; McGhee, Charles N J; Patel, Dipika V

2014-01-01

This study aimed to investigate changes in visual acuity, corneal parameters, and topographic parameters after pterygium surgery. A prospective observational study was conducted. Twenty eyes of 20 participants undergoing pterygium excision with conjunctival autograft secured using human fibrin tissue adhesive were included in the study. All the participants were assessed preoperatively and 1 and 3 months postoperatively. The parameters included subjective refraction, visual acuity, and pterygium size (pterygium horizontal corneal length [PHCL]) and corneal tomography by Pentacam rotating Scheimpflug tomographer (OCULUS Optikgeräte GmbH, Wetzlar, Germany). The astigmatic changes were calculated using vector analysis. The mean age of participants was 49.3 ± 12.1 years. Mean PHCL was 2.68 ± 0.30 mm. The mean best corrected visual acuity preoperatively was 6/7.5, improving significantly to 6/6 at 1 month (P = 0.001) with this improvement remaining stable at 3 months postoperatively (P = 0.34). There was no significant change in subjective astigmatism, however, mean topographic astigmatism decreased significantly at 1 month (4.36 diopter, P < 0.01) and remained unchanged at 3 months (P < 0.01). Greater PHCL was associated with greater changes in corneal astigmatism. Significant improvements and early stabilization of visual acuity and topographic astigmatism confirm the optical benefits of pterygium excision. These data also suggest a significant advantage of performing pterygium before rather than simultaneously with or after cataract surgery by enabling the most accurate biometry.

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

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.

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.

Customized Corneal Cross-Linking-A Mathematical Model.

PubMed

Caruso, Ciro; Epstein, Robert L; Ostacolo, Carmine; Pacente, Luigi; Troisi, Salvatore; Barbaro, Gaetano

2017-05-01

To improve the safety, reproducibility, and depth of effect of corneal cross-linking with the ultraviolet A (UV-A) exposure time and fluence customized according to the corneal thickness. Twelve human corneas were used for the experimental protocol. They were soaked using a transepithelial (EPI-ON) technique using riboflavin with the permeation enhancer vitamin E-tocopheryl polyethylene glycol succinate. The corneas were then placed on microscope slides and irradiated at 3 mW/cm for 30 minutes. The UV-A output parameters were measured to build a new equation describing the time-dependent loss of endothelial protection induced by riboflavin during cross-linking, as well as a pachymetry-dependent and exposure time-dependent prescription for input UV-A fluence. The proposed equation was used to establish graphs prescribing the maximum UV-A fluence input versus exposure time that always maintains corneal endothelium exposure below toxicity limits. Analysis modifying the Lambert-Beer law for riboflavin oxidation leads to graphs of the maximum safe level of UV-A radiation fluence versus the time applied and thickness of the treated cornea. These graphs prescribe UV-A fluence levels below 1.8 mW/cm for corneas of thickness 540 μm down to 1.2 mW/cm for corneas of thickness 350 μm. Irradiation times are typically below 15 minutes. The experimental and mathematical analyses establish the basis for graphs that prescribe maximum safe fluence and UV-A exposure time for corneas of different thicknesses. Because this clinically tested protocol specifies a corneal surface clear of shielding riboflavin on the corneal surface during UV-A irradiation, it allows for shorter UV-A irradiation time and lower fluence than in the Dresden protocol.

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.

Multimodal Assessment of Corneal Thinning Using Optical Coherence Tomography, Scheimpflug Imaging, Pachymetry, and Slit-Lamp Examination.

PubMed

Oatts, Julius T; Keenan, Jeremy D; Mannis, Tova; Lietman, Tom M; Rose-Nussbaumer, Jennifer

2017-04-01

To assess the relationship between corneal thinning measured by clinician-graded slit-lamp examination compared with ultrasound pachymetry (USP), anterior segment optical coherence tomography (AS-OCT), and the Pentacam. Patients with corneal thinning underwent USP, AS-OCT, Pentacam measurements and standardized clinical grading by 2 cornea specialists estimating thinning on slit-lamp examination. Reproducibility of each testing modality was assessed using the intraclass correlation coefficient. Bland-Altman plots were used to determine precision and limits of agreement (LOA) between imaging modalities and clinical grading. We included 22 patients with corneal thinning secondary to infectious or inflammatory keratitis. Mean percent stromal thinning estimated by grader 1 was 51% (SD 31) and grader 2 was 49% (SD 33). The intraclass correlation coefficient between the masked examiners was 0.95 (95% confidence interval, 0.88-0.98). Graders were more similar to each other than to any other modality with 2% difference and 4.6% of measurements outside the LOA. When measuring the area of maximum thinning, AS-OCT measured approximately 10% thicker than human graders while the Pentacam measured approximately 10% thinner than human graders with 16.7% outside the LOA. USP measured approximately 20% thinner than human graders with 5.6% outside the LOA. Trained corneal specialists have a high degree of agreement in location and degree of corneal thinning when measured in a standardized fashion on the same day. Other testing modalities had acceptable reproducibility and agreement with clinical examination and each other, although Scheimpflug imaging fared worse for corneal thinning, particularly in the periphery, than the other modalities.

[Effect of flavin adenine dinucleotide on ultraviolet B induced damage in cultured human corneal epithelial cells].

PubMed

Sakamoto, Asuka; Nakamura, Masatsugu

2012-01-01

This study evaluated the effects of flavin adenine dinucleotide (FAD) on ultraviolet B (UV-B)-induced damage in cultured human corneal epithelial (HCE-T) cells. The cultured HCE-T cells were treated with 0.003125-0.05% FAD before exposure to 80 mJ/cm2 UV-B. Cell viability was measured 24 h after UV-B irradiation using the MTS assay. Reactive oxygen species (ROS) were detected 30 min after UV-B irradiation using 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate acetyl ester. Apoptosis was evaluated 4 h after UV-B irradiation in the caspase-3/7 activity assay. UV-B irradiation reduced cell viability and stimulated ROS production and caspase-3/7 activity in HCE-T cells. Pretreatment of UV-B irradiated HCE-T cells with FAD significantly attenuated cell viability reduction and inhibited the stimulation of both ROS production and caspase-3/7 activity due to UV-B exposure compared with those with vehicle (0% FAD). These results clarified that FAD inhibits ROS-mediated apoptosis by UV-B irradiation in HCE-T cells and suggest that FAD may be effective as a radical scavenger in UV-B-induced corneal damage.

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.

Occurrence of viral DNA in paired samples of corneal rim and cornea preservation fluid.

PubMed

Broniek, G; Langwińska-Wośko, E; Sybilska, M; Szaflik, J P; Przybylski, M; Wróblewska, M

2017-04-01

Corneal transplants have one of the highest success rates among all transplantological procedures. Corneas intended for transplantation are stored in a preservation fluid, which is then tested for bacterial and fungal infections. Among all analyses of infectious complications following corneal transplants, infections caused by bacteria or fungi are the most prominent. Surprisingly, however, apart from a few publications, there is a lack of data regarding the occurrence of viruses in donor corneas and the risk of transmitting these to their recipients. The intention of this research was therefore to determine the frequency with which human herpesvirus 1 (HHV-1), human herpesvirus 2 (HHV-2), and human adenovirus (HAdV) occur in transplanted corneal tissue, as well as in samples of preservation fluid. The study comprised 57 paired samples, with each pair consisting of a fragment of the corneal tissue remaining after its trepanation for transplantation surgery and a sample of corneal preservation fluid. Sample pairs were all tested for the presence of the DNA of three viruses (HHV-1, HHV-2, and HAdV) using real time PCR technique. Viral DNA was found in three of the tested corneas-HHV-1 DNA in one paired sample (1.8%) and adenovirus DNA in two single samples (3.5%). We postulate that virological testing of corneas for transplantation should be considered, particularly in the case of donors with increased risk factors for herpesvirus and adenovirus reactivation. J. Med. Virol. 89:732-736, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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.

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.

The structural and optical properties of type III human collagen biosynthetic corneal substitutes

PubMed Central

Hayes, Sally; Lewis, Phillip; Islam, M. Mirazul; Doutch, James; Sorensen, Thomas; White, Tomas; Griffith, May; Meek, Keith M.

2015-01-01

The structural and optical properties of clinically biocompatible, cell-free hydrogels comprised of synthetically cross-linked and moulded recombinant human collagen type III (RHCIII) with and without the incorporation of 2-methacryloyloxyethyl phosphorylcholine (MPC) were assessed using transmission electron microscopy (TEM), X-ray scattering, spectroscopy and refractometry. These findings were examined alongside similarly obtained data from 21 human donor corneas. TEM demonstrated the presence of loosely bundled aggregates of fine collagen filaments within both RHCIII and RHCIII-MPC implants, which X-ray scattering showed to lack D-banding and be preferentially aligned in a uniaxial orientation throughout. This arrangement differs from the predominantly biaxial alignment of collagen fibrils that exists in the human cornea. By virtue of their high water content (90%), very fine collagen filaments (2–9 nm) and lack of cells, the collagen hydrogels were found to transmit almost all incident light in the visible spectrum. They also transmitted a large proportion of UV light compared to the cornea which acts as an effective UV filter. Patients implanted with these hydrogels should be cautious about UV exposure prior to regrowth of the epithelium and in-growth of corneal cells into the implants. PMID:26159106

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.

Prototheca wickerhamii infection of a corneal graft.

PubMed

Solky, Ana C; Laver, Nora M V; Williams, Joseph; Fraire, Armando

2011-10-01

Algae are generally noninfectious agents in mammals, with few known pathogenic algae. Prototheca is an achlorophylic nonphotosynthetic algae, globally ubiquitous, and readily isolated from rivers, lakes, ponds, and soil. Although canine and bovine protothecosis have been reported more widely, infections in humans are rare, particularly in patients with an intact immune system. The majority of protothecal infections in humans is associated with Prototheca wickerhamii. We report an unusual case of P. wickerhamii infection in an immunocompetent corneal transplant patient.

Involvement of NADPH oxidases in alkali burn-induced corneal injury.

PubMed

Gu, Xue-Jun; Liu, Xian; Chen, Ying-Ying; Zhao, Yao; Xu, Man; Han, Xiao-Jian; Liu, Qiu-Ping; Yi, Jing-Lin; Li, Jing-Ming

2016-07-01

Chemical burns are a major cause of corneal injury. Oxidative stress, inflammatory responses and neovascularization after the chemical burn aggravate corneal damage, and lead to loss of vision. Although NADPH oxidases (Noxs) play a crucial role in the production of reactive oxygen species (ROS), the role of Noxs in chemical burn-induced corneal injury remains to be elucidated. In the present study, the transcription and expression of Noxs in corneas were examined by RT-qPCR, western blot analysis and immunofluorescence staining. It was found that alkali burns markedly upregulated the transcription and expression of Nox2 and Nox4 in human or mouse corneas. The inhibition of Noxs by diphenyleneiodonium (DPI) or apocynin (Apo) effectively attenuated alkali burn-induced ROS production and decreased 3-nitrotyrosine (3-NT) protein levels in the corneas. In addition, Noxs/CD11b double‑immunofluorescence staining indicated that Nox2 and Nox4 were partially co-localized with CD11b. DPI or Apo prevented the infiltration of CD11b-positive inflammatory cells, and inhibited the transcription of inflammatory cytokines following alkali burn-induced corneal injury. In our mouse model of alkali burn-induced corneal injury, corneal neovascularization (CNV) occurred on day 3, and it affected 50% of the whole area of the cornea on day 7, and on day 14, CNV coverage of the cornea reached maximum levels. DPI or Apo effectively attenuated alkali burn‑induced CNV and decreased the mRNA levels of angiogenic factors, including vascular endothelial growth factor (VEGF), VEGF receptors and matrix metalloproteinases (MMPs). Taken together, our data indicate that Noxs play a role in alkali burn-induced corneal injury by regulating oxidative stress, inflammatory responses and CNV, and we thus suggest that Noxs are a potential therapeutic target in the future treatment of chemical-induced corneal injury.

Heterogeneity in macular corneal dystrophy.

PubMed

Edward, D P; Yue, B Y; Sugar, J; Thonar, E J; SunderRaj, N; Stock, E L; Tso, M O

1988-11-01

Macular corneal dystrophy is an autosomal recessive disorder in which abnormal deposits in the corneal stroma have been identified. We examined the corneal buttons of 12 patients, who had clinical features of macular dystrophy, by histochemical staining, transmission electron microscopy, and immunohistochemical techniques. All corneas exhibited positive staining with Muller Mowry's colloidal iron. Using monoclonal antibodies 1/20/5-D-4, J-10, J-19, and J-36 that recognize specific sites on the sulfated keratan sulfate molecule, we stained corneal sections by an avidin-biotin-peroxidase complex method and identified two groups of macular corneal dystrophy. One group consisting of four corneas reacted positively with all four antibodies, and the other group consisting of eight corneas did not react with any of the antibodies used. These results confirmed those recently presented by Yang et al that there may be subgroups of macular dystrophy that can be identified by immunohistochemical methods. Also, serum levels of sulfated keratan sulfate were determined in seven patients. One patient who displayed a normal level of serum keratan sulfate had positive corneal immunoreactivity. Of the six patients who lacked serum keratan sulfate, four showed negative and two had positive corneal immunostaining, suggesting at least three subgroups in the disease. An attempt was made to correlate the clinical features, histochemical-staining characteristics, and ultrastructural morphology with the immunoreactivity to keratan sulfate antibodies, but no correlations could be made.

The Evolution of Corneal Transplantation.

PubMed

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

2017-12-15

BACKGROUND The aim of this study was to investigate the evolution of surgical methods in and leading indications for corneal transplantation from 2005 to 2016. MATERIAL AND METHODS Data from the corneal graft waiting list and from all keratoplasties carried out between 2005 and 2016 at the University Eye Hospital Tübingen were retrospectively evaluated. RESULTS A total of 1259 keratoplasties were performed between 2005 and 2016 at the University Eye Hospital Tübingen. The most common surgical indications for corneal transplantation were Fuchs endothelial corneal dystrophy (45.5%) and keratoconus (14.2%). The mean rate of corneal transplantations almost doubled from 71 keratoplasties per year in the first 6-year period to 139 keratoplasties per year in the second 6-year period (P=0.005). The number of penetrating keratoplasties remained similar. The number of Descemet membrane endothelial keratoplasties (DMEK) increased significantly from 2008 to 2016 (P<0.0001). One DMEK procedure was performed in 2008 (representing 1.4% of all transplantations), while 75 DMEK procedures were performed in 2016 (representing 60.5% of all transplantations) (P<0.0001). DMEK became the favored surgical method for endothelial disorders, exceeding penetrating keratoplasty in 2013. CONCLUSIONS Our study shows evolutionary changes in preferred corneal transplantation techniques and leading indications for keratoplasty from 2005 to 2016. Since its introduction a decade ago, DMEK is currently the golden standard in the management of corneal endothelial dysfunction.

A fully automated cell segmentation and morphometric parameter system for quantifying corneal endothelial cell morphology.

PubMed

Al-Fahdawi, Shumoos; Qahwaji, Rami; Al-Waisy, Alaa S; Ipson, Stanley; Ferdousi, Maryam; Malik, Rayaz A; Brahma, Arun

2018-07-01

Corneal endothelial cell abnormalities may be associated with a number of corneal and systemic diseases. Damage to the endothelial cells can significantly affect corneal transparency by altering hydration of the corneal stroma, which can lead to irreversible endothelial cell pathology requiring corneal transplantation. To date, quantitative analysis of endothelial cell abnormalities has been manually performed by ophthalmologists using time consuming and highly subjective semi-automatic tools, which require an operator interaction. We developed and applied a fully-automated and real-time system, termed the Corneal Endothelium Analysis System (CEAS) for the segmentation and computation of endothelial cells in images of the human cornea obtained by in vivo corneal confocal microscopy. First, a Fast Fourier Transform (FFT) Band-pass filter is applied to reduce noise and enhance the image quality to make the cells more visible. Secondly, endothelial cell boundaries are detected using watershed transformations and Voronoi tessellations to accurately quantify the morphological parameters of the human corneal endothelial cells. The performance of the automated segmentation system was tested against manually traced ground-truth images based on a database consisting of 40 corneal confocal endothelial cell images in terms of segmentation accuracy and obtained clinical features. In addition, the robustness and efficiency of the proposed CEAS system were compared with manually obtained cell densities using a separate database of 40 images from controls (n = 11), obese subjects (n = 16) and patients with diabetes (n = 13). The Pearson correlation coefficient between automated and manual endothelial cell densities is 0.9 (p < 0.0001) and a Bland-Altman plot shows that 95% of the data are between the 2SD agreement lines. We demonstrate the effectiveness and robustness of the CEAS system, and the possibility of utilizing it in a real world clinical setting to

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

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.

On the use of Orbscan II to assess the peripheral corneal thickness in humans: a comparison with ultrasound pachometry measures.

PubMed

Jonuscheit, Sven; Doughty, Michael J; Button, Norman F

2007-03-01

To compare the measures of corneal thickness measurements obtained by an optical scanning slit method with those obtained by an ultrasound (US) pachometer, with special interest in the mid-peripheral (2.5 mm from centre) and peripheral (4.5 mm from centre) region of the cornea. Three measures of corneal thickness were taken using Orbscan II and then by US pachometry (under topical anaesthesia with benoxinate 0.4%) on 24 adults, aged 20-58 years and with up to 8.5 D of myopia. The full Orbscan topography maps were used to extract single point data along the horizontal corneal meridian for the geometric centre, 2.5 mm from centre (nasal and temporal) and 4.5 mm (nasal and temporal) from centre. No correction factor was used for the Orbscan data. The same set of measures were made with the US pachometer. In all cases, the averages of three (centre) or six (mid-periphery and periphery) readings were taken as the measurements from each cornea. Orbscan readings on the right eyes averaged 0.576, 0.632 and 0.712 mm for central, mid-peripheral and peripheral sites with average values for emmetropic subjects (<1 DS, n = 12) being marginally higher than for myopic subjects (average - 4.00 DS, n = 12). For US pachometry, the average values were however 0.522, 0.554 and 0.606 mm. Similar results were obtained on left eyes. Combining data from both eyes also showed that the mean difference between Orbscan II and US measures was not constant across the cornea, being 0.055 +/- 0.014 mm at the centre, 0.080 +/- 0.019 mm at mid-peripheral locations and 0.107 +/- 0.046 mm at the peripheral sites. These differences persisted after application of the generally recommended acoustic factor (x0.92) to all of the Orbscan readings. A single acoustic factor correction cannot be applied to all corneal thickness measures made with an Orbscan II to equate the measures to those made with an US pachometer.

Using genipin-crosslinked acellular porcine corneal stroma for cosmetic corneal lens implants.

PubMed

Liu, Zhao; Zhou, Qiang; Zhu, Jixiang; Xiao, Jianhui; Wan, Pengxia; Zhou, Chenjing; Huang, Zheqian; Qiang, Na; Zhang, Wei; Wu, Zheng; Quan, Daping; Wang, Zhichong

2012-10-01

Acellular porcine corneal stroma (APCS) has been proven to maintain the matrix microenvironment and is therefore an ideal biomaterial for the repair and reconstruction of corneal stroma. This study aims to develop a method to prepare cosmetic corneal lens implants for leukoma using genipin-crosslinked APCS (Gc-APCS). The Gc-APCS was prepared from APCS immersed in 1.0% genipin aqueous solution (pH 5.5) for 4 h at 37 °C, followed by lyophilization at -10 °C. The color of the Gc-APCS gradually deepened to dark-blue. The degree of crosslinking was 45.7 ± 4.6%, measured by the decrease of basic and hydroxy amino acids. The porous structure and ultrastructure of collagenous lamellae were maintained, and the porosity and BET SSA were 72.7 ± 4.6% and 23.01 ± 3.45 m(2)/g, respectively. The Gc-APCS rehydrated to the physiological water content within 5 min and was highly resistant to collagenase digestion. There were no significant differences in the areal modulus and curvature variation between Gc-APCS and nature porcine cornea. The dark-blue pigments were stable to pH, light and implantation in vivo. Gc-APCS extracts had no inhibitory effects on the proliferation of keratocytes. Corneal neovascularization, graft degradation and corneal rejection were not observed within 6 months. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mucin Characteristics of Human Corneal-Limbal Epithelial Cells that Exclude the Rose Bengal Anionic Dye

PubMed Central

Argüeso, Pablo; Tisdale, Ann; Spurr-Michaud, Sandra; Sumiyoshi, Mika; Gipson, Ilene K.

2005-01-01

Purpose Rose bengal is an organic anionic dye used to assess damage of the ocular surface epithelium in ocular surface disease. It has been proposed that mucins have a protective role, preventing rose bengal staining of normal ocular surface epithelial cells. The current study was undertaken to evaluate rose bengal staining in a human corneal-limbal epithelial (HCLE) cell line known to produce and glycosylate membrane-associated mucins. Methods HCLE cells were grown to confluence in serum-free medium and switched to DMEM/F12 with 10% serum to promote differentiation. Immunolocalization of the membrane-associated mucins MUC1 and MUC16 and the T-antigen carbohydrate epitope was performed with the monoclonal antibodies HMFG-2 and OC125 and jacalin lectin, respectively. To assess dye uptake, cultures were incubated for 5 minutes with 0.1% rose bengal and photographed. To determine whether exclusion of negatively charged rose bengal requires a negative charge at the cell surface, cells were incubated with fluoresceinated cationized ferritin. The effect of hyperosmotic stress on rose bengal staining in vitro was evaluated by increasing the ion concentration (Ca+2 and Mg+2) in the rose bengal uptake assay. Results The cytoplasm and nucleus of confluent HCLE cells cultured in media without serum, lacking the expression of MUC16 but not MUC1, as well as human corneal fibroblasts, which do not express mucins, stained with rose bengal. Culture of HCLE cells in medium containing serum resulted in the formation of islands of stratified cells that excluded rose bengal. Apical cells of the stratified islands produced MUC16 and the T-antigen carbohydrate epitope on their apical surfaces. Colocalization experiments demonstrated that fluoresceinated cationized ferritin did not bind to these stratified cells, indicating that rose bengal is excluded from cells that lack negative charges. Increasing the amounts of divalent cations in the media reduced the cellular area protected

Effects of nicotine on corneal wound healing following acute alkali burn.

PubMed

Kim, Jong Won; Lim, Chae Woong; Kim, Bumseok

2017-01-01

Epidemiological studies have indicated that smoking is a pivotal risk factor for the progression of several chronic diseases. Nicotine, the addictive component of cigarettes, has powerful pathophysiological properties in the body. Although the effects of cigarette smoking on corneal re-epithelialization have been studied, the effects of nicotine on corneal wound healing-related neovascularization and fibrosis have not been fully demonstrated. The aim of this study was to evaluate the effects of chronic administration of nicotine on corneal wound healing following acute insult induced by an alkali burn. BALB/C female mice randomly received either vehicle (2% saccharin) or nicotine (100 or 200 μg/ml in 2% saccharin) in drinking water ad libitum. After 1 week, animals were re-randomized and the experimental group was subjected to a corneal alkali burn, and then nicotine was administered until day 14 after the alkali burn. A corneal alkali burn model was generated by placing a piece of 2 mm-diameter filter paper soaked in 1N NaOH on the right eye. Histopathological analysis and the expression level of the pro-angiogenic genes vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP9) revealed that chronic nicotine administration enhanced alkali burn-induced corneal neovascularization. Furthermore, the mRNA expression of the pro-fibrogenic factors α-smooth muscle actin (αSMA), transforming growth factor-β (TGF-β), and collagen α1 (Col1) was enhanced in the high-concentration nicotine-treated group compared with the vehicle group after corneal injury. Immunohistochemical analysis also showed that the αSMA-positive area was increased in chronic nicotine-treated mice after corneal alkali burn. An in vitro assay found that expression of the α3, α7, and β1 nicotinic acetylcholine receptor (nAChR) subunits was significantly increased by chemical injury in human corneal fibroblast cells. Moreover, alkali-induced fibrogenic gene expression and

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

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

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.

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

Methods Development for the Isolation and Culture of Primary Corneal Endothelial Cells

DTIC Science & Technology

2017-02-01

1989 Yue et al. described methods that reached a 59% success rate in supporting human CEC growth using corneal tissue obtained from donors over 20...delayed-onset mustard gas keratitis: report of 48 patients and review of literature. Ophthalmology 2005; 112(4): 617-25. 6. Kadar T, Dachir S, Cohen L...toxicity following corneal exposure to sulfur mustard vapor. Invest Ophthalmol Vis Sci 2013; 54(10): 6735-44. 9. Kadar T, Cohen M, Cohen L, et al

Interventions for recurrent corneal erosions.

PubMed

Watson, Stephanie L; Lee, Ming-Han H; Barker, Nigel H

2012-09-12

Recurrent corneal erosion is a common cause of disabling ocular symptoms and predisposes the cornea to infection. It may follow corneal trauma. Measures to prevent the development of recurrent corneal erosion following corneal trauma have not been firmly established. Once recurrent corneal erosion develops simple medical therapy (standard treatment) may lead to resolution of the episode. However, some patients continue to suffer when such therapy fails and once resolved further episodes of recurrent erosion may occur. A number of treatment and prophylactic options are then available but there is no agreement as to the best option. To assess the effectiveness and safety of prophylactic and treatment regimens for recurrent corneal erosion. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 6), MEDLINE (January 1946 to June 2012), EMBASE (January 1980 to June 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to June 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 13 June 2012. We also contacted researchers in the field. We included randomised and quasi-randomised trials that compared a prophylactic or treatment regimen with another prophylaxis/treatment or no prophylaxis/treatment for patients with recurrent corneal erosion. Two authors independently extracted data and assessed trial quality. We contacted study authors for additional information. Seven randomised and one quasi-randomised controlled trial were included in the review. The trials were heterogenous and of poor quality. Safety data presented were incomplete. For the treatment of recurrent

Corneal Thickness in Highlanders.

PubMed

Patyal, Sagarika; Arora, Amit; Yadav, Arun; Sharma, Vijay K

2017-03-01

Patyal, Sagarika, Amit Arora, Arun Yadav, and Vijay K. Sharma. Corneal thickness in highlanders. High Alt Med Biol. 18:56-60, 2017. Corneal thickness is an important parameter with diagnostic and therapeutic implications. Various studies have highlighted increase in corneal thickness in lowlanders on ascending to high altitude. However, there are no studies in the published literature pertaining to corneal thickness of the highlanders who are inhabitants of such altitudes. Hence, study was carried out with objective to determine the corneal thickness of highlanders living at heights of more than 11,000 feet and compare it with corneal thickness of lowlanders. The highlander participants of the study consisted of inhabitants of Ladakh region of India at an altitude of 11,000 feet or more and lowlander participants consisted of inhabitants at an altitude of 1500 feet. A total of 254 highlanders and 212 lowlanders participated. A mean of 25 measurements of central corneal thickness (CCT) of every participant was obtained for each eye using ultrasonic pachymeter. The mean age of the participants was 41.8 (15.9) and 47.7 (17.7) years among lowlanders and highlanders, respectively. The highlanders had 11.95 μm lower mean CCT reading compared to lowlanders after adjusting for age and sex (p value <0.001). There was no statistically significant difference in mean CCT readings of right eye and left eye in either lowlanders or highlanders. Age also had a significant effect after adjustment for location and gender (p = 0.001). CCT decreased by 0.31 μm with every year increase in the age. Gender had no statistically significant effect. This study found statistically significant difference in CCT measurements between highlanders and lowlanders. The thinner corneas of highlanders may have a bearing on diagnosis and treatment of glaucoma, refractive surgery, contact lens fitting implantation of Intacs, and astigmatic keratectomy done on such patients. The study also

Noninvasive spectroscopic diagnosis of superficial ocular lesions and corneal infections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mourant, J.R.; Bigio, I.J.; Johnson, T.

The potential of a rapid noninvasive diagnostic system to detect tissue abnormalities on the surface of the eye has been investigated. The optical scatter signal from lesions and normal areas on the conjunctival sclera of the human eye were measured in vivo. It is possible to distinguish nonpigmented pingueculas from other lesions. The ability of the system to detect malignancies could not be tested because none of the measured and biopsied lesions were malignant. Optical scatter and fluorescence spectra of bacterial and fungal suspensions, and corneal irritations were also collected. Both scattering and fluorescence show potential for diagnosing corneal infections.

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.

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

Corneal erosion and Kindler syndrome.

PubMed

Signes-Soler, Isabel; Rodriguez-Prats, Jose Luis; Carbonell, Stella; Tañá-Rivero, Pedro

2013-01-01

To describe a very common corneal pathology in a patient with Kindler syndrome. We report the case of a 21-year-old woman, who presented to the Ophthalmology Department as an emergency presentation because of ocular pain in the left eye that radiated to other areas of the face and neck. After an exhaustive clinical interview, it was determined that the patient had a rare disease (Kindler syndrome). Ophthalmologic examination revealed corneal erosion on the left eye. No other significant conditions were found. After the application of conventional treatment, the corneal integrity was completely restored. We describe a very rare syndrome. Although conventional treatment restored corneal integrity, it is important to remember that ocular signs and symptoms are often associated with systemic pathologies.

Adipose Derived Stem Cells for Corneal Wound Healing after Laser Induced Corneal Lesions in Mice.

PubMed

Zeppieri, Marco; Salvetat, Maria Letizia; Beltrami, Antonio; Cesselli, Daniela; Russo, Rossella; Alcalde, Ignacio; Merayo-Lloves, Jesús; Brusini, Paolo; Parodi, Pier Camillo

2017-12-05

The aim of our study was to assess the clinical effectiveness of topical adipose derived stem cell (ADSC) treatment in laser induced corneal wounds in mice by comparing epithelial repair, inflammation, and histological analysis between treatment arms. Corneal lesions were performed on both eyes of 40 mice by laser induced photorefractive keratectomy. All eyes were treated with topical azythromycin bid for three days. Mice were divided in three treatment groups ( n = 20), which included: control, stem cells and basic serum; which received topical treatment three times daily for five consecutive days. Biomicroscope assessments and digital imaging were performed by two masked graders at 30, 54, 78, 100, and 172 h to analyze extent of fluorescein positive epithelial defect, corneal inflammation, etc. Immunohistochemical techniques were used in fixed eyes to assess corneal repair markers Ki67, α Smooth Muscle Actin (α-SMA) and E-Cadherin. The fluorescein positive corneal lesion areas were significantly smaller in the stem cells group on days 1 ( p < 0.05), 2 ( p < 0.02) and 3. The stem cell treated group had slightly better and faster re-epithelization than the serum treated group in the initial phases. Comparative histological data showed signs of earlier and better corneal repair in epithelium and stromal layers in stem cell treated eyes, which showed more epithelial layers and enhanced wound healing performance of Ki67, E-Cadherin, and α-SMA. Our study shows the potential clinical and histological advantages in the topical ADSC treatment for corneal lesions in mice.

Adipose Derived Stem Cells for Corneal Wound Healing after Laser Induced Corneal Lesions in Mice

PubMed Central

Salvetat, Maria Letizia; Beltrami, Antonio; Cesselli, Daniela; Russo, Rossella; Merayo-Lloves, Jesús; Brusini, Paolo; Parodi, Pier Camillo

2017-01-01

The aim of our study was to assess the clinical effectiveness of topical adipose derived stem cell (ADSC) treatment in laser induced corneal wounds in mice by comparing epithelial repair, inflammation, and histological analysis between treatment arms. Corneal lesions were performed on both eyes of 40 mice by laser induced photorefractive keratectomy. All eyes were treated with topical azythromycin bid for three days. Mice were divided in three treatment groups (n = 20), which included: control, stem cells and basic serum; which received topical treatment three times daily for five consecutive days. Biomicroscope assessments and digital imaging were performed by two masked graders at 30, 54, 78, 100, and 172 h to analyze extent of fluorescein positive epithelial defect, corneal inflammation, etc. Immunohistochemical techniques were used in fixed eyes to assess corneal repair markers Ki67, α Smooth Muscle Actin (α-SMA) and E-Cadherin. The fluorescein positive corneal lesion areas were significantly smaller in the stem cells group on days 1 (p < 0.05), 2 (p < 0.02) and 3. The stem cell treated group had slightly better and faster re-epithelization than the serum treated group in the initial phases. Comparative histological data showed signs of earlier and better corneal repair in epithelium and stromal layers in stem cell treated eyes, which showed more epithelial layers and enhanced wound healing performance of Ki67, E-Cadherin, and α-SMA. Our study shows the potential clinical and histological advantages in the topical ADSC treatment for corneal lesions in mice. PMID:29206194

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 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.

Diabetic corneal neuropathy.

PubMed Central

Schultz, R O; Peters, M A; Sobocinski, K; Nassif, K; Schultz, K J

1983-01-01

Corneal epithelial lesions can be found in approximately one-half of asymptomatic patients with diabetes mellitus. These lesions are transient and clinically resemble the keratopathy seen in staphylococcal keratoconjunctivitis. Staphylococcal organisms, however, can be isolated in equal percentages from diabetic patients without keratopathy. Diabetic peripheral neuropathy was found to be related to the presence of diabetic keratopathy after adjusting for age with analysis of covariance. The strongest predictor of both keratopathy and corneal fluorescein staining was vibration perception threshold in the toes (P less than 0.01); and the severity of keratopathy was directly related to the degree of diminution of peripheral sensation. Other predictors of keratopathy were: reduced tear breakup time (P less than 0.03), type of diabetes (P less than 0.01), and metabolic status as indicated by c-peptide fasting (P less than 0.01). No significant relationships were found between the presence of keratopathy and tear glucose levels, endothelial cell densities, corneal thickness measurements, the presence of S epidermidis, or with duration of disease. It is our conclusion that asymptomatic epithelial lesions in the nontraumatized diabetic cornea can occur as a manifestation of generalized polyneuropathy and probably represent a specific form of corneal neuropathy. Images FIGURE 1 FIGURE 2 FIGURE 3 PMID:6676964

Corneal edema after phacoemulsification

PubMed Central

Sharma, Namrata; Singhal, Deepali; Nair, Sreelakshmi P; Sahay, Pranita; Sreeshankar, SS; Maharana, Prafulla Kumar

2017-01-01

Phacoemulsification is the most commonly performed cataract surgery in this era. With all the recent advances in investigations and management of cataract through phacoemulsification, most of the patients are able to achieve excellent visual outcome. Corneal edema after phacoemulsification in the immediate postoperative period often leads to patient dissatisfaction and worsening of outcome. Delayed onset corneal edema often warrants endothelial keratoplasty. This review highlights the etiopathogenesis, risk factors, and management of corneal edema in the acute phase including descemet's membrane detachment (DMD) and toxic anterior segment syndrome. Various investigative modalities such as pachymetry, specular microscopy, anterior segment optical coherence tomography, and confocal microscopy have been discussed briefly. PMID:29208818

Corneal complications of vernal keratoconjunctivitis.

PubMed

Solomon, Abraham

2015-10-01

Vernal keratoconjunctivitis (VKC) is a severe bilateral chronic allergic inflammatory disease of the ocular surface. In most of the cases, the disease is limited to the tarsal conjunctiva and to the limbus. However, in the more severe cases, the cornea may be involved, leading to potentially sight threatening complications. Prompt recognition of these complications is crucial in the management of VKC, which is one of the most severe ocular allergic diseases. A vicious cycle of inflammation occurs as a result of a set of reciprocal interactions between the conjunctiva and the cornea, which results in damage to the corneal epithelium and corneal stoma, and to the formation of shield ulcers and plaques, infectious keratitis, keratoconus, scarring, and limbal stem cell deficiency. These corneal complications can cause permanent decrease or loss of vision in children suffering from VKC. Corneal complications in VKC are the result of an on-going process of uncontrolled inflammation. Proper recognition of the corneal complications in VKC is crucial, as most of these can be managed or prevented by a combination of medical and surgical measures.

Early wound healing of laser in situ keratomileusis-like flaps after treatment with human corneal stromal stem cells.

PubMed

Morgan, Siân R; Dooley, Erin P; Kamma-Lorger, Christina; Funderburgh, James L; Funderburgh, Martha L; Meek, Keith M

2016-02-01

To use a well-established organ culture model to investigate the effects of corneal stromal stem cells on the optical and biomechanical properties of corneal wounds after laser in situ keratomileusis (LASIK)-like flap creation. School of Optometry and Vision Sciences, Cardiff University, Cardiff, Wales, United Kingdom. Experimental study. The LASIK-like flaps were produced in sheep corneas. The flap beds were treated with corneal stromal stem cells and were then replaced and allowed to heal for different periods of up to 3 weeks in organ culture. The optical transmission of the cornea, the force required to detach the flap, and the presence of myofibroblasts near the flap bed were measured. Corneal stromal stem cell-treated flap beds were statistically significantly more transparent after 3 weeks in culture than the untreated controls. At 3 weeks, the mean force necessary to detach the flap was more than twice the force required for the respective control samples. Concurrently, there were 44% activated cells immediately below the flap margin of the controls compared with 29% in the same region of the corneal stromal stem cell-treated flaps. In this system, the presence of corneal stromal stem cells at the wound margin significantly increased the adherence of LASIK-like flaps while maintaining corneal transparency. It is postulated that this is achieved by the deposition of extracellular connective tissue similar to that found in the normal cornea and by the paucity of activated keratocytes (myofibroblasts), which are known to scatter a significant amount of the incident light. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Controlling human corneal stromal stem cell contraction to mediate rapid cell and matrix organization of real architecture for 3-dimensional tissue equivalents.

PubMed

Mukhey, Dev; Phillips, James B; Daniels, Julie T; Kureshi, Alvena K

2018-02-01

The architecture of the human corneal stroma consists of a highly organized extracellular matrix (ECM) interspersed with keratocytes. Their progenitor cells; corneal stromal stem cells (CSSC) are located at the periphery, in the limbal stroma. A highly organized corneal ECM is critical for effective transmission of light but this structure may be compromised during injury or disease, resulting in loss of vision. Re-creating normal organization in engineered tissue equivalents for transplantation often involves lengthy culture times that are inappropriate for clinical use or utilisation of synthetic substrates that bring complications such as corneal melting. CSSC have great therapeutic potential owing to their ability to reorganize a disorganized matrix, restoring transparency in scarred corneas. We examined CSSC contractile behavior to assess whether this property could be exploited to rapidly generate cell and ECM organization in Real Architecture For 3D Tissues (RAFT) tissue equivalents (TE) for transplantation. Free-floating collagen gels were characterized to assess contractile behavior of CSSC and establish optimum cell density and culture times. To mediate cell and collagen organization, tethered collagen gels seeded with CSSC were cultured and subsequently stabilized with the RAFT process. We demonstrated rapid creation of biomimetic RAFT TE with tunable structural properties. These displayed three distinct regions of varying degrees of cellular and collagen organization. Interestingly, increased organization coincided with a dramatic loss of PAX6 expression in CSSC, indicating rapid differentiation into keratocytes. The organized RAFT TE system could be a useful bioengineering tool to rapidly create an organized ECM while simultaneously controlling cell phenotype. For the first time, we have demonstrated that human CSSC exhibit the phenomenon of cellular self-alignment in tethered collagen gels. We found this mediated rapid co-alignment of collagen fibrils

Thermal and infrared-diode laser effects on indocyanine-green-treated corneal collagen

NASA Astrophysics Data System (ADS)

Timberlake, George T.; Patmore, Ann; Shallal, Assaad; McHugh, Dominic; Marshall, John

1993-07-01

It has been suggested that laser welds of collagenous tissues form by interdigitation and chemical bonding of thermally 'unraveled' collagen fibrils. We investigated this proposal by attempting to weld highly collagenous, avascular corneal tissue with an infrared (IR) diode laser as follows. First, the temperature at which corneal collagen shrinks and collagen fibrils 'split' into subfibrillary components was determined. Second, since use of a near-IR laser wavelength necessitated addition of an absorbing dye (indocyanine green (ICG) to the cornea, we measured absorption spectra of ICG-treated tissue to ensure that peak ICG absorbance did not change markedly when ICG was present in the cornea. Third, using gel electrophoresis of thermally altered corneal collagen, we searched for covalently crosslinked compounds predicted by the proposed welding mechanism. Finally, we attempted to weld partial thickness corneal incisions infused with ICG. Principal experimental findings were as follows: (1) Human corneal (type I) collagen splits into subfibrillary components at approximately 63 degree(s)C, the same temperature that produces collagen shrinkage. (2) Peak ICG absorption does not change significantly in corneal stroma or with laser heating. (3) No evidence was found for the formation of novel compounds or the loss of proteins as a result of tissue heating. All tissue treated with ICG, however, exhibited a novel 244 kD protein band indicating chemical activity between collagen and corneal stromal components. (4) Laser welding corneal incisions was unsuccessful possibly due to shrinkage of the sides of the incision, lack of incision compression during heating, or a less than optimal combination of ICG concentration and radiant exposure. In summary, these experiments demonstrate the biochemical and morphological complexity of ICG-enhanced IR laser-tissue welding and the need for further investigation of laser welding mechanisms.

Adipose-Derived Mesenchymal Stem Cell Administration Does Not Improve Corneal Graft Survival Outcome

PubMed Central

Fuentes-Julián, Sherezade; Arnalich-Montiel, Francisco; Jaumandreu, Laia; Leal, Marina; Casado, Alfonso; García-Tuñon, Ignacio; Hernández-Jiménez, Enrique; López-Collazo, Eduardo; De Miguel, Maria P.

2015-01-01

The effect of local and systemic injections of mesenchymal stem cells derived from adipose tissue (AD-MSC) into rabbit models of corneal allograft rejection with either normal-risk or high-risk vascularized corneal beds was investigated. The models we present in this study are more similar to human corneal transplants than previously reported murine models. Our aim was to prevent transplant rejection and increase the length of graft survival. In the normal-risk transplant model, in contrast to our expectations, the injection of AD-MSC into the graft junction during surgery resulted in the induction of increased signs of inflammation such as corneal edema with increased thickness, and a higher level of infiltration of leukocytes. This process led to a lower survival of the graft compared with the sham-treated corneal transplants. In the high-risk transplant model, in which immune ocular privilege was undermined by the induction of neovascularization prior to graft surgery, we found the use of systemic rabbit AD-MSCs prior to surgery, during surgery, and at various time points after surgery resulted in a shorter survival of the graft compared with the non-treated corneal grafts. Based on our results, local or systemic treatment with AD-MSCs to prevent corneal rejection in rabbit corneal models at normal or high risk of rejection does not increase survival but rather can increase inflammation and neovascularization and break the innate ocular immune privilege. This result can be partially explained by the immunomarkers, lack of immunosuppressive ability and immunophenotypical secretion molecules characterization of AD-MSC used in this study. Parameters including the risk of rejection, the inflammatory/vascularization environment, the cell source, the time of injection, the immunosuppression, the number of cells, and the mode of delivery must be established before translating the possible benefits of the use of MSCs in corneal transplants to clinical practice. PMID

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.

Randomized Trial Comparing Amniotic Membrane Transplantation with Lamellar Corneal Graft for the Treatment of Corneal Thinning.

PubMed

de Farias, Charles C; Allemann, Norma; Gomes, José Á P

2016-04-01

There are few studies comparing different surgical procedures for the treatment of corneal thinning. Lamellar corneal transplantation (LCT) has been reported to be efficient, but its results can be jeopardized by allograft rejection, opacification, or high astigmatism. Amniotic membrane transplantation (AMT) has been considered a good alternative, but it is not as resistant as LCT and the tissue can be reabsorbed after surgery. A prospective, randomized, interventional, and comparative study of consecutive patients with corneal thinning over 6 months was performed. Ophthalmological examination was performed before transplant surgery and then repeated 1, 7, 15, 30, 90, and 180 days after surgery and ultrasound biomicroscopy was performed before and then 30, 90, and 180 days after surgery to assess corneal thinning. Herpes simplex infection was the main cause of corneal thinning (9 eyes), followed by surgery (cataract, glaucoma, 5 cases), rheumatoid arthritis (1), chemical burn (1), perforating trauma (1), previous band keratopathy treatment (1), and Stevens-Johnson syndrome (1). Although all patients showed significant increase in final thickness in the area of thinning, it was higher in those submitted to LCT at 180 days postoperatively. Regardless of the surgical technique, all patients showed epithelialization. Patients undergoing AMT showed an 89% decrease in neovascularization. Final corrected distance visual acuity was better in patients submitted to AMT. LCT proved to be the best option for treating corneal thinning. AMT represents an alternative that allows good visual recovery but does not restore corneal thickness as efficiently as LCT.

Corneal anesthetic abuse and Candida keratitis.

PubMed

Chern, K C; Meisler, D M; Wilhelmus, K R; Jones, D B; Stern, G A; Lowder, C Y

1996-01-01

Topical corneal anesthetic abuse is a self-inflicted injury, causing profound corneal morbidity. Superimposed infection is an important complicating factor. The authors report four patients with confirmed topical anesthetic abuse of the cornea, in whom Candida keratitis developed. A retrospective review of the medical records of four patients with confirmed topical corneal anesthetic abuse and fungal keratitis. A 21-year-old woman, two 28-year-old women, and a 35-year-old man were included in the study. All these patients sustained a corneal injury, prompting the chronic use of topical anesthetics (0.5% proparacaine hydrochloride in 3 patients, and 0.5% tetracaine hydrochloride and 0.4% benoxinate hydrochloride in the other). Corneal findings included epithelial defects in all patients, focal infiltrate in one patient, and ring-shaped stromal infiltrate in three patients. Topical anesthetic was discontinued, all patients initially were treated empirically with antibacterial agents, and three patients received topical corticosteroids. Subsequent corneal cultures grew Candida spp, Candida albicans specifically in three patients, and local and systemic antifungal therapy was started. Corneas in two patients re-epithelialized; a conjunctival flap was performed on another patient with a descemetocele; and the remaining patient was lost to follow-up, although repeat fungal cultures yielded no growth. Corneal superinfection with Candida may occur during topical anesthetic abuse. Therapy includes discontinuation of the anesthetic and institution of antifungal therapy.

Keratoconus corneal architecture after riboflavin/ultraviolet A cross-linking: Ultrastructural studies

PubMed Central

Almubrad, Turki; Paladini, Iacopo; Mencucci, Rita

2013-01-01

Purpose Study to investigate the effects of collagen cross-linking on the ultrastructural organization of the corneal stroma in the human keratoconus cornea (KC). Methods Three normal, three keratoconus (KC1, KC2, KC3), and three cross-linked keratoconus (CXL1, CXL2, CXL3) corneas were analyzed. The KC corneas were treated with a riboflavin-ultraviolet A (UVA) treatment (CXL) method described by Wollensak et al. Penetrating keratoplasty (PKP) was performed 6 months after treatment. All samples were processed for electron microscopy. Results The riboflavin-UVA-treated CXL corneal stroma showed interlacing lamellae in the anterior stroma followed by well-organized parallel running lamellae. The lamellae contained uniformly distributed collagen fibrils (CFs) decorated with normal proteoglycans (PGs). The CF diameter and interfibrillar spacing in the CXL cornea were significantly increased compared to those in the KC cornea. The PG area in the CXL corneas were significantly smaller than the PGs in the KC cornea. The epithelium and Bowman’s layer were also normal. On rare occasions, a thick basement membrane and collagenous pannus were also observed. Conclusions Corneal cross-linking leads to modifications of the cornea stroma. The KC corneal structure showed a modification in the CF diameter, interfibrillar spacing, and PG area. This resulted in a more uniform distribution of collagen fibrils, a key feature for corneal transparency. PMID:23878503

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.

[Recent studies on corneal epithelial barrier function].

PubMed

Liu, F F; Li, W; Liu, Z G; Chen, W S

2016-08-01

Corneal epithelium, the outermost layer of eyeball, is the main route for foreign materials to enter the eye. Under physiological conditions, the corneal epithelial superficial cells form a functionally selective permeability barrier. Integral corneal epithelial barrier function not only ensures the enrolling of nutrients which is required for regular metabolism, but also prevents foreign bodies, or disease-causing microorganism invasion. Recently, a large number of clinical and experimental studies have shown that abnormal corneal epithelial barrier function is the pathological basis for many ocular diseases. In addition, some study found that corneal epithelial barrier constitutes a variety of proteins involved in cell proliferation, differentiation, apoptosis, and a series of physiological and pathological processes. This paper reviewed recent studies specifically on the corneal epithelial barrier, highlights of its structure, function and influence factors. (Chin J Ophthalmol, 2016, 52: 631-635).

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.

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

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

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

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.

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

[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 collagen crosslinking for corneal ectasia of post-LASIK: one-year results

PubMed Central

Li, Gang; Fan, Zheng-Jun; Peng, Xiu-Jun

2012-01-01

AIM To evaluate the efficacy and safety of corneal collagen crosslinking (CXL) to prevent the progression of post-laser in situ keratomileusis (LASIK) corneal ectasia. METHODS In a prospective, nonrandomized, single-centre study, CXL was performed in 20 eyes of 11 patients who had LASIK for myopic astigmatism and subsequently developed keratectasia.The procedure included instillation of 0.1% riboflavin-20% dextrane solution 30 minutes before UVA irradiation and every 5 minutes for an additional 30 minutes during irradiation. The eyes were evaluated preoperatively and at 1-, 3-, 6-, and 12-month intervals. The complete ophthalmologic examination comprised uncorrected visual acuity, best spectacle-corrected visual acuity, endothelial cell count, ultrasound pachymetry, corneal topography, and in vivo confocal microscopy. RESULTS CXL appeared to stabilise or partially reverse the progression of post-LASIK corneal ectasia without apparent complication in our cohort. UCVA and BCVA improvements were statistically significant(P<0.05) beyond 12 months after surgery (improvement of 0.07 and 0.13 logMAR at 1 year, respectively). Mean baseline flattest meridian keratometry and mean steepest meridian keratometry reduction (improvement of 2.00 and 1.50 diopters(D), respectively) were statistically significant (P<0.05) at 12 months postoperatively. At 1 year after CXL, mean endothelial cell count did not deteriorate. Mean thinnest cornea pachymetry increased significantly. CONCLUSION The results of the study showed a long-term stability of post-LASIK corneal ectasia after crosslinking without relevant side effects. It seems to be a safe and promising procedure to stop the progression of post-LASIK keratectasia, thereby avoiding or delaying keratoplasty. PMID:22762048

Corneal power evaluation after myopic corneal refractive surgery using artificial neural networks.

PubMed

Koprowski, Robert; Lanza, Michele; Irregolare, Carlo

2016-11-15

Efficacy and high availability of surgery techniques for refractive defect correction increase the number of patients who undergo to this type of surgery. Regardless of that, with increasing age, more and more patients must undergo cataract surgery. Accurate evaluation of corneal power is an extremely important element affecting the precision of intraocular lens (IOL) power calculation and errors in this procedure could affect quality of life of patients and satisfaction with the service provided. The available device able to measure corneal power have been tested to be not reliable after myopic refractive surgery. Artificial neural networks with error backpropagation and one hidden layer were proposed for corneal power prediction. The article analysed the features acquired from the Pentacam HR tomograph, which was necessary to measure the corneal power. Additionally, several billion iterations of artificial neural networks were conducted for several hundred simulations of different network configurations and different features derived from the Pentacam HR. The analysis was performed on a PC with Intel ® Xeon ® X5680 3.33 GHz CPU in Matlab ® Version 7.11.0.584 (R2010b) with Signal Processing Toolbox Version 7.1 (R2010b), Neural Network Toolbox 7.0 (R2010b) and Statistics Toolbox (R2010b). A total corneal power prediction error was obtained for 172 patients (113 patients forming the training set and 59 patients in the test set) with an average age of 32 ± 9.4 years, including 67% of men. The error was at an average level of 0.16 ± 0.14 diopters and its maximum value did not exceed 0.75 dioptres. The Pentacam parameters (measurement results) providing the above result are tangential anterial/posterior. The corneal net power and equivalent k-reading power. The analysis time for a single patient (a single eye) did not exceed 0.1 s, whereas the time of network training was about 3 s for 1000 iterations (the number of neurons in the hidden layer was 400).

Topographic corneal changes after collagen cross-linking in patients with corneal keratoconus.

PubMed

Razmjoo, Hasan; Nasrollahi, Alireza Peyman Kobra; Salam, Hasan; Karbasi, Najmeh; Najarzadegan, Mohammad Reza

2013-10-01

Corneal collagen cross-linking with riboflavin, also known as collagen cross-linking (CXL), involves the application of riboflavin solution to the eye that is activated by illumination with ultraviolet A (UVA) light. We survey here the topographic corneal changes one year after CXL in patients with corneal keratoconus. This prospective randomized clinical trial study comprised 66 patients with progression of keratoconus during one year who were enrolled at Feiz University Referral Eye Center in Isfahan. Before and after the operation, patients were examined with slit lamp and funduscopic examinations and measurement of uncorrected visual acuity (UCVA), and best spectacle-corrected visual acuity (BSCVA) was done with a logarithm of minimal angle of resolution (logMAR) scale. Corneal topographic and pachymetry values were derived from Orbscan II. The paired t-test test was used for statistical analyses with SPSS software version 20 (SPSS Inc., Chicago, IL, USA). All 66 patients completed postoperative follow-up at 12 months. The mean age of the patients was 22.4 ± 5.4 years (range: 18-29 years). Thirty-six (54.55%) subjects were men and 30 (45.45%) were women. The mean preoperative sphere was -2.66 ± 2.14 diopter (D), the mean cylinder was -3.97 ± 2.29, and the mean spherical equivalent (SE) was -4.64 ± 2.56. Postoperatively, the mean sphere was -2.22 ± 2.57 D, the mean cylinder was -3.60 ± 2.40 D, and SE was -4.02 ± 2.93 D (P = 0.037). SE also demonstrated a mean difference of 0.62 ± 0.37 D significantly (P = 0.006). The mean diameter of preoperative posterior best-fit sphere (BFS) was 6.33 ± 0.35mm (range: 5.51-7.73 mm) before operation, and it improved to 6.28 ± 0.34mm (range: 4.36-6.13 mm) after operation; the difference was significant (P = 0.039). Our study showed a significant improvement in topographic corneal changes and refractive results in patients with corneal ectasia after CXL.

Fabrication of a corneal model composed of corneal epithelial and endothelial cells via a collagen vitrigel membrane functioned as an acellular stroma and its application to the corneal permeability test of chemicals.

PubMed

Yamaguchi, Hiroyuki; Takezawa, Toshiaki

2018-05-29

A collagen vitrigel membrane (CVM) we developed can function as both a scaffold for cells and a pathway for chemicals. To extrapolate the corneal permeability of chemicals in vivo, we proposed six corneal models using the CVM. Thin and thick CVMs were utilized as models for Bowman's membrane (BM) and an acellular-stroma (AS), respectively. Models for a corneal epithelium (CEpi), a corneal epithelium-acellular stroma (CEpi-AS), a corneal epithelium-endothelium (CEpi-Endo) and a corneal epithelium-acellular stroma-endothelium (CEpi-AS-Endo) were fabricated by culturing corneal epithelial cells and/or corneal endothelial cells on the surface of CVMs. Subsequently, the permeability coefficient (P app ) value of each model was calculated using five chemicals with different molecular radii; cyanocobalamin and four FITC-dextrans (FD-4, FD-10, FD-20 and FD-40). The slopes of P app versus molecular radii of those chemicals in the both BM and AS models were almost similar to data using an excised rabbit corneal stroma. The ratios of P app values in models for BM, CEpi and CEpi-Endo against those in data using an excised rabbit cornea were calculated as 75.4, 6.4 and 4.5-folds for FD-4 and 38.7, 10.0 and 4.2-folds for FD-10, respectively. Similarly, those in models for AS, CEpi-AS and CEpi-AS-Endo were calculated as 26.1, 2.5 and 0.6-folds for FD-4 and 26.1, 1.5 and 0.6-folds for FD-10, respectively. These results suggest that the CEpi-AS-Endo model with both the barrier function of corneal cell layers and the diffusion capacity of chemicals in thick CVM is most appropriate for extrapolating the corneal permeability of chemicals in vivo . The American Society for Pharmacology and Experimental Therapeutics.

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

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.

The Antifibrosis Effects of Peroxisome Proliferator-Activated Receptor δ on Rat Corneal Wound Healing after Excimer Laser Keratectomy.

PubMed

Gu, Yun; Li, Xuan; He, Tiangeng; Jiang, Zhixin; Hao, Peng; Tang, Xin

2014-01-01

Corneal stromal fibrosis characterized by myofibroblasts and abnormal extracellular matrix (ECM) is usually the result of inappropriate wound healing. The present study tested the hypothesis that the ligand activation of peroxisome proliferator-activated receptor (PPAR) δ had antifibrosis effects in a rat model of corneal damage. Adult Sprague-Dawley rats underwent bilateral phototherapeutic keratectomy (PTK). The eyes were randomized into four groups: PBS, GW501516 (a selective agonist of PPARδ), GSK3787 (a selective antagonist of PPARδ), or GW501516 combined with GSK3787. The agents were subconjunctivally administered twice a week until sacrifice. The cellular aspects of corneal wound healing were evaluated with in vivo confocal imaging and postmortem histology. A myofibroblast marker (α-smooth muscle actin) and ECM production (fibronectin, collagen type III and collagen type I) were examined by immunohistochemistry and RT-PCR. At the early stages of wound healing, GW501516 inhibited reepithelialization and promoted angiogenesis. During the remodeling phase of wound healing, GW501516 attenuated the activation and proliferation of keratocytes, which could be reversed by GSK3787. GW501516 decreased transdifferentiation from keratocytes into myofibroblasts, ECM synthesis, and corneal haze. These results demonstrate that GW501516 controls corneal fibrosis and suggest that PPARδ may potentially serve as a therapeutic target for treating corneal scars.

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.

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.

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

Acanthamoeba-Cytopathic Protein Induces Apoptosis and Proinflammatory Cytokines in Human Corneal Epithelial Cells by cPLA2α Activation

PubMed Central

Tripathi, Trivendra; Smith, Ashley Dawn; Abdi, Mahshid; Alizadeh, Hassan

2012-01-01

Purpose. We have shown that Acanthamoeba interacts with a mannosylated protein on corneal epithelial cells and stimulates trophozoites to secrete a mannose-induced 133 kDa protease (MIP-133), which facilitates corneal invasion and induces apoptosis. The mechanism of MIP-133–induced apoptosis is unknown. The aim of this study was to determine if MIP-133 induces apoptosis and proinflammatory cytokines/chemokines in human corneal epithelial (HCE) cells via the cytosolic phospholipase A2α (cPLA2α) pathway. Methods. HCE cells were incubated with or without MIP-133 at doses of 7.5, 15, and 50 μg/mL for 6, 12, and 24 hours. The effects of cPLA2α inhibitors on cPLA2α, arachidonic acid (AA) release, and apoptosis were tested in vitro. Inhibition of cPLA2α involved preincubating HCE cells for 1 hour with cPLA2α inhibitors (10 μM methyl-arachidonyl fluorophosphonate [MAFP] or 20 μM arachidonyl trifluoromethyl ketone [AACOCF3]) with or without MIP-133 for 24 hours. Expression of cPLA2α mRNA and enzyme was examined by RT-PCR and cPLA2 activity assays, respectively. Apoptosis of corneal epithelial cells was determined by caspase-3 and DNA fragmentation assays. Expression of IL-8, IL-6, IL-1β, and IFN-γ was examined by RT-PCR and ELISA. Results. MIP-133 induced significant cPLA2α (approximately two to four times) and AA release (approximately six times) from corneal cells while cPLA2α inhibitors significantly reduced cPLA2α (approximately two to four times) and AA release (approximately three times) (P < 0.05). cPLA2α inhibitors significantly inhibited MIP-133–induced DNA fragmentation approximately 7 to 12 times in HCE cells (P < 0.05). MIP-133 specifically activates cPLA2α enzyme activity in HCE cells, which is blocked by preincubation with anti–MIP-133 antibody. In addition, MIP-133 induced significant IL-8, IL-6, IL-1β, and IFN-γ production, approximately two to three times (P < 0.05). Conclusions. MIP-133 interacts with phospholipids on plasma

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.

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.

Effect of central corneal thickness, corneal curvature, and axial length on applanation tonometry.

PubMed

Kohlhaas, Markus; Boehm, Andreas G; Spoerl, Eberhard; Pürsten, Antje; Grein, Hans J; Pillunat, Lutz E

2006-04-01

To evaluate the effect of central corneal thickness (CCT), corneal curvature, and axial length on applanation tonometry in an in vivo study. In a masked, prospective clinical trial, we examined 125 eyes of 125 patients scheduled for cataract surgery. Corneal curvature was measured by means of keratometry and axial length by A-scan ultrasonography. By cannulating the anterior chamber before surgery, intraocular pressure (IOP) was set to 20, 35, and 50 mm Hg in a closed system by means of a water column. After measuring thickness, the IOP was measured with an applanation tonometer. Pearson product moment correlations and multiple linear regression analyses were performed, and significance levels were evaluated by the paired, 2-tailed t test. The difference between measured and real IOP was significantly dependent (P < .001) on CCT. The associations between IOP and corneal curvature or IOP and axial length were not statistically significant (P = .31). The association between IOP reading and CCT is shown in the "Dresdner correction table," which illustrates an approximately 1-mm Hg correction for every 25-microm deviation from a CCT of 550 microm. The correction values were positive as thickness decreased and negative as thickness increased. Central corneal thickness significantly affects IOP readings obtained by applanation tonometry according to the Goldmann principle. A correction of IOP readings by considering CCT according to the Dresdner correction table might be helpful for determining an accurate IOP value.

Capsaicin-responsive corneal afferents do not contain TRPV1 at their central terminals in trigeminal nucleus caudalis in rats.

PubMed

Hegarty, Deborah M; Hermes, Sam M; Largent-Milnes, Tally M; Aicher, Sue A

2014-11-01

We examined the substrates for ocular nociception in adult male Sprague-Dawley rats. Capsaicin application to the ocular surface in awake rats evoked nocifensive responses and suppressed spontaneous grooming responses. Thus, peripheral capsaicin was able to activate the central pathways encoding ocular nociception. Our capsaicin stimulus evoked c-Fos expression in a select population of neurons within rostral trigeminal nucleus caudalis in anesthetized rats. These activated neurons also received direct contacts from corneal afferent fibers traced with cholera toxin B from the corneal surface. However, the central terminals of the corneal afferents that contacted capsaicin-activated trigeminal neurons did not contain TRPV1. To determine if TRPV1 expression had been altered by capsaicin stimulation, we examined TRPV1 content of corneal afferents in animals that did not receive capsaicin stimulation. These studies confirmed that while TRPV1 was present in 30% of CTb-labeled corneal afferent neurons within the trigeminal ganglion, TRPV1 was only detected in 2% of the central terminals of these corneal afferents within the trigeminal nucleus caudalis. Other TRP channels were also present in low proportions of central corneal afferent terminals in unstimulated animals (TRPM8, 2%; TRPA1, 10%). These findings indicate that a pathway from the cornea to rostral trigeminal nucleus caudalis is involved in corneal nociceptive transmission, but that central TRP channel expression is unrelated to the type of stimulus transduced by the peripheral nociceptive endings. Copyright © 2014 Elsevier B.V. All rights reserved.

Progress in corneal wound healing

PubMed Central

Ljubimov, Alexander V.; Saghizadeh, Mehrnoosh

2015-01-01

Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal epithelium, and

Progress in corneal wound healing.

PubMed

Ljubimov, Alexander V; Saghizadeh, Mehrnoosh

2015-11-01

Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β (TGF-β) system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal

Kinetics of corneal thermal shrinkage

NASA Astrophysics Data System (ADS)

Borja, David; Manns, Fabrice; Lee, William E.; Parel, Jean-Marie

2004-07-01

Purpose: The purpose of this study was to determine the effects of temperature and heating duration on the kinetics of thermal shrinkage in corneal strips using a custom-made shrinkage device. Methods: Thermal shrinkage was induced and measured in corneal strips under a constant load placed while bathed in 25% Dextran irrigation solution. A study was performed on 57 Florida Lions Eye Bank donated human cadaver eyes to determine the effect of temperature on the amount and rate of thermal shrinkage. Further experiments were performed on 20 human cadaver eyes to determine the effects of heating duration on permanent shrinkage. Data analysis was performed to determine the effects of temperature, heating duration, and age on the amount and kinetics of shrinkage. Results: Shrinkage consisted of two phases: a shrinkage phase during heating and a regression phase after heating. Permanent shrinkage increased with temperature and duration. The shrinkage and regression time constants followed Arrhenius type temperature dependence. The shrinkage time constants where calculated to be 67, 84, 121, 560 and 1112 (s) at 80, 75, 70, 65, and 60°C respectively. At 65°C the permanent shrinkage time constant was calculated to be 945s. Conclusion: These results show that shrinkage treatments need to raise the temperature of the tissue above 75°C for several seconds in order to prevent regression of the shrinkage effect immediately after treatment and to induce the maximum amount of permanent irreversible shrinkage.

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.

Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis

PubMed Central

Soler, Vincent José; Tran-Viet, Khanh-Nhat; Galiacy, Stéphane D; Limviphuvadh, Vachiranee; Klemm, Thomas Patrick; St Germain, Elizabeth; Fournié, Pierre R; Guillaud, Céline; Maurer-Stroh, Sebastian; Hawthorne, Felicia; Suarez, Cyrielle; Kantelip, Bernadette; Afshari, Natalie A; Creveaux, Isabelle; Luo, Xiaoyan; Meng, Weihua; Calvas, Patrick; Cassagne, Myriam; Arné, Jean-Louis; Rozen, Steven G; Malecaze, François; Young, Terri L

2014-01-01

Background Corneal intraepithelial dyskeratosis is an extremely rare condition. The classical form, affecting Native American Haliwa-Saponi tribe members, is called hereditary benign intraepithelial dyskeratosis (HBID). Herein, we present a new form of corneal intraepithelial dyskeratosis for which we identified the causative gene by using deep sequencing technology. Methods and results A seven member Caucasian French family with two corneal intraepithelial dyskeratosis affected individuals (6-year-old proband and his mother) was ascertained. The proband presented with bilateral complete corneal opacification and dyskeratosis. Palmoplantar hyperkeratosis and laryngeal dyskeratosis were associated with the phenotype. Histopathology studies of cornea and vocal cord biopsies showed dyskeratotic keratinisation. Quantitative PCR ruled out 4q35 duplication, classically described in HBID cases. Next generation sequencing with mean coverage of 50× using the Illumina Hi Seq and whole exome capture processing was performed. Sequence reads were aligned, and screened for single nucleotide variants and insertion/deletion calls. In-house pipeline filtering analyses and comparisons with available databases were performed. A novel missense mutation M77T was discovered for the gene NLRP1 which maps to chromosome 17p13.2. This was a de novo mutation in the proband’s mother, following segregation in the family, and not found in 738 control DNA samples. NLRP1 expression was determined in adult corneal epithelium. The amino acid change was found to destabilise significantly the protein structure. Conclusions We describe a new corneal intraepithelial dyskeratosis and how we identified its causative gene. The NLRP1 gene product is implicated in inflammation, autoimmune disorders, and caspase mediated apoptosis. NLRP1 polymorphisms are associated with various diseases. PMID:23349227

The effects of subconjunctival bupivacaine, lidocaine, and mepivacaine on corneal sensitivity in healthy horses.

PubMed

Jinks, Maggie R; Fontenot, Robin L; Wills, Robert W; Betbeze, Caroline M

2017-12-12

To compare the efficacy and duration of effect of three local anesthetics on corneal sensitivity when administered subconjunctivally in horses. Eight healthy adult horses. A randomized, masked, crossover study design was used, with a two-week washout period between trials. The subconjunctival space of the randomly selected eye was injected with 0.2 mLs of bupivacaine (0.5%), lidocaine (2%), mepivacaine (2%), or saline. All horses received each medication once. The contralateral eye served as a control. The corneal touch threshold (CTT) was measured in both eyes with a Cochet-Bonnet esthesiometer prior to sedation with xylazine, after sedation, and at 10-min intervals after subconjunctival injection until corneal sensitivity returned to baseline. The total time of decreased CTT and the maximum decrease in CTT were compared for each medication using a general linear mixed model (P < 0.05). Total time of decreased CTT was 105.0 min for bupivacaine, 103.8 min for lidocaine, 138.8 min for mepivacaine, and 7.5 min for saline. All local anesthetics decreased CTT longer than saline (P < 0.001) and mepivacaine decreased CTT longer than lidocaine (P = 0.04). The mean minimum CTT was 1.67 cm for bupivacaine, 1.42 cm for lidocaine, and 0.73 cm for mepivacaine, which were all significantly less (P < 0.001) than saline (4.73 cm). No evidence of corneal toxicity was noted with any treatment. Subconjunctival injections of lidocaine, bupivacaine, and mepivacaine effectively and safely reduce corneal sensitivity in eyes of healthy horses for 1.5-2 h, and may be useful for providing perioperative analgesia for equine corneal procedures. © 2017 American College of Veterinary Ophthalmologists.

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.

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.

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/

Evaluating the effectiveness of treatment of corneal ulcers via computer-based automatic image analysis

NASA Astrophysics Data System (ADS)

Otoum, Nesreen A.; Edirisinghe, Eran A.; Dua, Harminder; Faraj, Lana

2012-06-01

Corneal Ulcers are a common eye disease that requires prompt treatment. Recently a number of treatment approaches have been introduced that have been proven to be very effective. Unfortunately, the monitoring process of the treatment procedure remains manual and hence time consuming and prone to human errors. In this research we propose an automatic image analysis based approach to measure the size of an ulcer and its subsequent further investigation to determine the effectiveness of any treatment process followed. In Ophthalmology an ulcer area is detected for further inspection via luminous excitation of a dye. Usually in the imaging systems utilised for this purpose (i.e. a slit lamp with an appropriate dye) the ulcer area is excited to be luminous green in colour as compared to rest of the cornea which appears blue/brown. In the proposed approach we analyse the image in the HVS colour space. Initially a pre-processing stage that carries out a local histogram equalisation is used to bring back detail in any over or under exposed areas. Secondly we deal with the removal of potential reflections from the affected areas by making use of image registration of two candidate corneal images based on the detected corneal areas. Thirdly the exact corneal boundary is detected by initially registering an ellipse to the candidate corneal boundary detected via edge detection and subsequently allowing the user to modify the boundary to overlap with the boundary of the ulcer being observed. Although this step makes the approach semi automatic, it removes the impact of breakages of the corneal boundary due to occlusion, noise, image quality degradations. The ratio between the ulcer area confined within the corneal area to the corneal area is used as a measure of comparison. We demonstrate the use of the proposed tool in the analysis of the effectiveness of a treatment procedure adopted for corneal ulcers in patients by comparing the variation of corneal size over time.

Optimization of immunolocalization of cell cycle proteins in human corneal endothelial cells.

PubMed

He, Zhiguo; Campolmi, Nelly; Ha Thi, Binh-Minh; Dumollard, Jean-Marc; Peoc'h, Michel; Garraud, Olivier; Piselli, Simone; Gain, Philippe; Thuret, Gilles

2011-01-01

En face observation of corneal endothelial cells (ECs) using flat-mounted whole corneas is theoretically much more informative than observation of cross-sections that show only a few cells. Nevertheless, it is not widespread for immunolocalization (IL) of proteins, probably because the endothelium, a superficial monolayer, behaves neither like a tissue in immunohistochemistry (IHC) nor like a cell culture in immunocytochemistry (ICC). In our study we optimized IL for ECs of flat-mounted human corneas to study the expression of cell cycle-related proteins. We systematically screened 15 fixation and five antigen retrieval (AR) methods on 118 human fresh or stored corneas (organ culture at 31 °C), followed by conventional immunofluorescence labeling. First, in an attempt to define a universal protocol, we selected combinations able to correctly localize four proteins that are perfectly defined in ECs (zonula occludens-1 [ZO-1] and actin) or ubiquitous (heterogeneous nuclear ribonucleoprotein L [hnRNP L] and histone H3). Second, we screened protocols adapted to the revelation of 9 cell cycle proteins: Ki67, proliferating cell nuclear antigen (PCNA), minichromosome maintenance protein 2 (MCM2), cyclin D1, cyclin E, cyclin A, p16(Ink4a), p21(Cip1) and p27(Kip1). Primary antibody controls (positive controls) were performed on both epithelial cells of the same, simultaneously-stained whole corneas, and by ICC on human ECs in in vitro non-confluent cultures. Both controls are known to contain proliferating cells. IL efficiency was evaluated by two observers in a masked fashion. Correct localization at optical microscopy level in ECs was define as clear labeling with no background, homogeneous staining, agreement with previous works on ECs and/or protein functions, as well as a meaningful IL in proliferating cells of both controls. The common fixation with 4% formaldehyde (gold standard for IHC) failed to reveal 12 of the 13 proteins. In contrast, they were all revealed

Corneal Thickness as a Predictor of Corneal Transplant Outcome

PubMed Central

Verdier, David D.; Sugar, Alan; Baratz, Keith; Beck, Roy; Dontchev, Mariya; Dunn, Steven; Gal, Robin L.; Holland, Edward J.; Kollman, Craig; Lass, Jonathan H.; Mannis, Mark J.; Penta, Jeffrey

2013-01-01

Purpose Assess corneal thickness (CT) and correlation with graft outcome after penetrating keratoplasty in the Cornea Donor Study. Methods 887 subjects with a corneal transplant for a moderate risk condition (principally Fuchs or pseudophakic corneal edema) had post-operative CT measurements throughout a 5 year follow up time. Relationships between baseline (recipient, donor, and operative) factors and CT were explored. Proportional hazards models were used to assess association between CT and graft failure. Relationship between CT and cell density was assessed with a longitudinal repeated measures model and Spearman correlation estimates. Results Higher longitudinal CT measurements were associated with diagnosis of pseudophakic or aphakic corneal edema (P<0.001), intraocular pressure > 25mmHg during the first post-operative month (P=0.003), white (non-Hispanic) donor race (P=0.002) and respiratory causes of donor death (P<0.001). Among those without graft failure within the first post-operative year, the 5-year cumulative incidence (±95% CI) of graft failure was 5% ± 5% in those with a 1-year CT ≤500μm, 5% ± 3% for CT 501 – 550μm, 7% ± 4% for CT 551 – 600μm and 20% ± 11% for CT >600μm. In multivariate analysis, both 1 year CT and cell density were associated with subsequent graft failure (P=0.002 and 0.009). CT increase was modestly associated with endothelial cell loss during follow up (r=-0.29). Conclusion During the first 5 years following penetrating keratoplasty, CT can serve as a predictor of graft survival. However, CT is not a substitute for cell density measurement as both measures were independently predictive of graft failure. PMID:23343949

Corneal cross-linking in 9 horses with ulcerative keratitis

PubMed Central

2013-01-01

Background Corneal ulcers are one of the most common eye problems in the horse and can cause varying degrees of visual impairment. Secondary infection and protease activity causing melting of the corneal stroma are always concerns in patients with corneal ulcers. Corneal collagen cross-linking (CXL), induced by illumination of the corneal stroma with ultraviolet light (UVA) after instillation of riboflavin (vitamin B2) eye drops, introduces crosslinks which stabilize melting corneas, and has been used to successfully treat infectious ulcerative keratitis in human patients. Therefore we decided to study if CXL can be performed in sedated, standing horses with ulcerative keratitis with or without stromal melting. Results Nine horses, aged 1 month to 16 years (median 5 years) were treated with a combination of CXL and medical therapy. Two horses were diagnosed with mycotic, 5 with bacterial and 2 with aseptic ulcerative keratitis. A modified Dresden-protocol for CXL could readily be performed in all 9 horses after sedation. Stromal melting, diagnosed in 4 horses, stopped within 24 h. Eight of nine eyes became fluorescein negative in 13.5 days (median time; range 4–26 days) days after CXL. One horse developed a bacterial conjunctivitis the day after CXL, which was successfully treated with topical antibiotics. One horse with fungal ulcerative keratitis and severe uveitis was enucleated 4 days after treatment due to panophthalmitis. Conclusions CXL can be performed in standing, sedated horses. We did not observe any deleterious effects attributed to riboflavin or UVA irradiation per se during the follow-up, neither in horses with infectious nor aseptic ulcerative keratitis. These data support that CXL can be performed in the standing horse, but further studies are required to compare CXL to conventional medical treatment in equine keratitis and to optimize the CXL protocol in this species. PMID:23803176

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

Corneal polarimetry after LASIK refractive surgery

NASA Astrophysics Data System (ADS)

Bueno, Juan M.; Berrio, Esther; Artal, Pablo

2006-01-01

Imaging polarimetry provides spatially resolved information on the polarization properties of a system. In the case of the living human eye, polarization could be related to the corneal biomechanical properties, which vary from the normal state as a result of surgery or pathologies. We have used an aberro-polariscope, which we recently developed, to determine and to compare the spatially resolved maps of polarization parameters across the pupil between normal healthy and post-LASIK eyes. The depolarization distribution is not uniform across the pupil, with post-surgery eyes presenting larger levels of depolarization. While retardation increases along the radius in normal eyes, this pattern becomes irregular after LASIK refractive surgery. The maps of slow axis also differ in normal and post-surgery eyes, with a larger disorder in post-LASIK eyes. Since these changes in polarization indicate subtle structural modifications of the cornea, this approach can be useful in a clinical environment to follow the biomechanical and optical changes of the cornea after refractive surgery or for the early diagnosis of different corneal pathologies.

Corneal biomechanical properties in healthy children measured by corneal visualization scheimpflug technology.

PubMed

He, Miao; Ding, Hui; He, Hong; Zhang, Chi; Liu, Liangping; Zhong, Xingwu

2017-05-17

The aim of this study was to evaluate corneal biomechanical properties in a population of healthy children in China using corneal visualization Scheimpflug technology (CST). All children underwent complete bi-ocular examinations. CST provided intraocular pressure (IOP) and corneal biomechanical parameters, including time, velocity, length and deformation amplitude at first applanation (A1T, A1V, A1L, A1DA), at second applanation (A2T, A2V, A2L, A2DA), highest concavity time (HCT), maximum deformation amplitude (MDA), peak distance (PD), and radius of curvature (RoC). Pearson correlation analysis was used to assess the impacts of demographic factors, central corneal thickness (CCT), spherical equivalent (SE), and IOP on corneal biomechanics. One hundred eight subjects (32 girls and 76 boys) with the mean age of 10.80 ± 4.13 years (range 4 to18 years) were included in the final analyses. The right and left eyes were highly symmetrical in SE (p = 0.082), IOP (p = 0.235), or CCT (p = 0.210). Mean A1T of the right eyes was 7.424 ± 0.340 ms; the left eyes 7.451 ± 0.365 ms. MDA was 0.993 ± 0.102 mm in the right eyes and 0.982 ± 0.100 mm in the left eyes. Mean HCT of the right eyes was 16.675 ± 0.502 ms; the left eyes 16.735 ± 0.555 ms. All CST parameters of both eye were remarkably symmetrical with the exception of A2L (p = 0.006), A1DA (p = 0.025). The majority of CST parameters of both eyes were significantly correlated with CCT and IOP (p < 0.05). However, age, SE, and sex exert little influence on the CST measurements. This study found interocular symmetry in corneal biomechanics in healthy children eyes. Several CST biomechanical parameters in children are modified by CCT and IOP.

Topographic corneal changes after collagen cross-linking in patients with corneal keratoconus

PubMed Central

Razmjoo, Hasan; Nasrollahi, Alireza Peyman Kobra; Salam, Hasan; Karbasi, Najmeh; Najarzadegan, Mohammad Reza

2013-01-01

Background: Corneal collagen cross-linking with riboflavin, also known as collagen cross-linking (CXL), involves the application of riboflavin solution to the eye that is activated by illumination with ultraviolet A (UVA) light. We survey here the topographic corneal changes one year after CXL in patients with corneal keratoconus. Materials and Methods: This prospective randomized clinical trial study comprised 66 patients with progression of keratoconus during one year who were enrolled at Feiz University Referral Eye Center in Isfahan. Before and after the operation, patients were examined with slit lamp and funduscopic examinations and measurement of uncorrected visual acuity (UCVA), and best spectacle-corrected visual acuity (BSCVA) was done with a logarithm of minimal angle of resolution (logMAR) scale. Corneal topographic and pachymetry values were derived from Orbscan II. The paired t-test test was used for statistical analyses with SPSS software version 20 (SPSS Inc., Chicago, IL, USA). Results: All 66 patients completed postoperative follow-up at 12 months. The mean age of the patients was 22.4 ± 5.4 years (range: 18-29 years). Thirty-six (54.55%) subjects were men and 30 (45.45%) were women. The mean preoperative sphere was −2.66 ± 2.14 diopter (D), the mean cylinder was −3.97 ± 2.29, and the mean spherical equivalent (SE) was −4.64 ± 2.56. Postoperatively, the mean sphere was −2.22 ± 2.57 D, the mean cylinder was −3.60 ± 2.40 D, and SE was −4.02 ± 2.93 D (P = 0.037). SE also demonstrated a mean difference of 0.62 ± 0.37 D significantly (P = 0.006). The mean diameter of preoperative posterior best-fit sphere (BFS) was 6.33 ± 0.35mm (range: 5.51-7.73 mm) before operation, and it improved to 6.28 ± 0.34mm (range: 4.36-6.13 mm) after operation; the difference was significant (P = 0.039). Conclusion: Our study showed a significant improvement in topographic corneal changes and refractive results in patients with corneal ectasia after CXL

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.

N-Acetylcysteine Increases Corneal Endothelial Cell Survival in a Mouse Model of Fuchs Endothelial Corneal Dystrophy

PubMed Central

Kim, Eun Chul; Meng, Huan; Jun, Albert S.

2014-01-01

The present study evaluated survival effects of N-acetylcysteine (NAC) on cultured corneal endothelial cells exposed to oxidative and endoplasmic reticulum (ER) stress and in a mouse model of early-onset Fuchs endothelial corneal dystrophy (FECD). Cultured bovine corneal endothelial cell viability against oxidative and ER stress was determined by CellTiter-Glo® luminescent reagent. Two-month-old homozygous knock-in Col8a2L450W/L450W mutant (L450W) and C57/Bl6 wild-type (WT) animals were divided into two groups of 15 mice. Group I received 7 mg/mL NAC in drinking water and Group II received control water for 7 months. Endothelial cell density and morphology were evaluated with confocal microscopy. Antioxidant gene (iNos) and ER stress/unfolded protein response gene (Grp78 and Chop) mRNA levels and protein expression were measured in corneal endothelium by real time PCR and Western blotting. Cell viability of H2O2 and thapsigargin exposed cells pre-treated with NAC was significantly increased compared to untreated controls (pitalic>0.01). Corneal endothelial cell density (CD) was higher (p=0.001) and percent polymegathism was lower (p=0.04) in NAC treated L450W mice than in untreated L450W mice. NAC treated L450W endothelium showed significant upregulation of iNos, whereas Grp78 and Chop were downregulated compared to untreated L450W endothelium by real time PCR and Western blotting. NAC increases survival in cultured corneal endothelial cells exposed against ER and oxidative stress. Systemic NAC ingestion increases corneal endothelial cell survival which is associated with increased antioxidant and decreased ER stress markers in a mouse model of early-onset FECD. Our study presents in vivo evidence of a novel potential medical treatment for FECD. PMID:24952277

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.

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.

Diabetic corneal neuropathy: clinical perspectives.

PubMed

Bikbova, Guzel; Oshitari, Toshiyuki; Baba, Takayuki; Bikbov, Mukharram; Yamamoto, Shuichi

2018-01-01

Diabetic keratopathy is characterized by impaired innervation of the cornea that leads to decreased sensitivity, with resultant difficulties with epithelial wound healing. These difficulties in wound healing put patients at risk for ocular complications such as surface irregularities, corneal infections, and stromal opacification. Pathological changes in corneal innervations in diabetic patients are an important early indicator of diabetic neuropathy. The decrease in corneal sensitivity is strongly correlated with the duration of diabetes as well as the severity of the neuropathy. This review presents recent findings in assessing the ocular surface as well as the recent therapeutic strategies for optimal management of individuals with diabetes who are susceptible to developing diabetic neuropathy.

Accelerated Development of Supramolecular Corneal Stromal-Like Assemblies from Corneal Fibroblasts in the Presence of Macromolecular Crowders.

PubMed

Kumar, Pramod; Satyam, Abhigyan; Fan, Xingliang; Rochev, Yury; Rodriguez, Brian J; Gorelov, Alexander; Joshi, Lokesh; Raghunath, Michael; Pandit, Abhay; Zeugolis, Dimitrios I

2015-07-01

Tissue engineering by self-assembly uses the cells' secretome as a regeneration template and biological factory of trophic factors. Despite the several advantages that have been witnessed in preclinical and clinical settings, the major obstacle for wide acceptance of this technology remains the tardy extracellular matrix formation. In this study, we assessed the influence of macromolecular crowding (MMC)/excluding volume effect, a biophysical phenomenon that accelerates thermodynamic activities and biological processes by several orders of magnitude, in human corneal fibroblast (HCF) culture. Our data indicate that the addition of negatively charged galactose derivative (carrageenan) in HCF culture, even at 0.5% serum, increases by 12-fold tissue-specific matrix deposition, while maintaining physiological cell morphology and protein/gene expression. Gene analysis indicates that a glucose derivative (dextran sulfate) may drive corneal fibroblasts toward a myofibroblast lineage. Collectively, these results indicate that MMC may be suitable not only for clinical translation and commercialization of tissue engineering by self-assembly therapies, but also for the development of in vitro pathophysiology models.

Transforming growth factor-{alpha} enhances corneal epithelial cell migration by promoting EGFR recycling.

PubMed

McClintock, Jennifer L; Ceresa, Brian P

2010-07-01

PURPOSE. The goal of this study was to determine the molecular mechanism by which transforming growth factor-alpha (TGF-alpha) is a more potent activator of epidermal growth factor receptor (EGFR)-mediated corneal wound healing than epidermal growth factor (EGF). METHODS. Telomerase immortalized human corneal epithelial (hTCEpi) cells and primary human corneal epithelial cells were tested for their ability to migrate in response to EGF and TGF-alpha. In parallel, the endocytic trafficking of the EGFR in response to these same ligands was examined using indirect immunofluorescence, immunoblots, and radioligand binding. RESULTS. TGF-alpha, compared with EGF, is a more potent activator of corneal epithelial cell migration. Although both TGF-alpha and EGF were able to induce EGFR internalization and phosphorylation, only those receptors that were stimulated with EGF progressed to lysosomal degradation. EGFRs stimulated with TGF-alpha recycled back to the plasma membrane, where they could be reactivated with ligand. CONCLUSIONS. This study reveals that EGFR-mediated cell migration is limited by ligand-stimulated downregulation of the EGFR. This limitation can be overcome by treating cells with TGF-alpha because TGF-alpha stimulates EGFR endocytosis, but not degradation. After internalization of the TGF-alpha/EGFR complex, EGFR recycles back to the plasma membrane, where it can be restimulated. This sequence of events provides the receptor multiple opportunities for stimulation. Thus, stimulation with TGF-alpha prolongs EGFR signaling compared with EGF.

Non-invasive measurement of corneal hydration.

PubMed

March, W F; Bauer, N J

2001-01-01

To investigate the feasibility of a confocal Raman spectroscopic technique for the noncontact assessment of corneal hydration in vivo in two legally blind subjects. A laser beam (632.8 nm; 15 mJ) was maintained on the cornea using a microscope objective lens (25x magnification, NA=0.5, f=10 mm) both for focusing the incident light as well as collecting the Raman backscattered light, in a 180 degrees backscatter configuration. An optical fiber, acting as the confocal pinhole for elimination of light from out-of-focus places, was coupled to a spectrometer that dispersed the collected light onto a sensitive array-detector for rapid spectral data acquisition over a range from 2,890 to 3,590 cm(-1). Raman spectra were recorded from the anterior 100 to 150 microm of the cornea over a period of time before and after topical application of a mild dehydrating solution. The ratio between the amplitudes of the signals at 3,400 cm(-1) (OH-vibrational mode of water) and 2,940 cm(-1) (CH-vibrational mode of proteins) was used as a measure of corneal hydration. High signal-to-noise ratio (SNR 25) Raman spectra were obtained from the human corneas using 15 mJ of laser light energy. Qualitative changes in the hydration of the anterior-most part of the corneas could be observed as a result of the dehydrating agent. Confocal Raman spectroscopy could potentially be applied clinically as a noncontact tool for the assessment of corneal hydration in vivo.

Femtosecond Lasers and Corneal Surgical Procedures.

PubMed

Marino, Gustavo K; Santhiago, Marcony R; Wilson, Steven E

2017-01-01

Our purpose is to present a broad review about the principles, early history, evolution, applications, and complications of femtosecond lasers used in refractive and nonrefractive corneal surgical procedures. Femtosecond laser technology added not only safety, precision, and reproducibility to established corneal surgical procedures such as laser in situ keratomileusis (LASIK) and astigmatic keratotomy, but it also introduced new promising concepts such as the intrastromal lenticule procedures with refractive lenticule extraction (ReLEx). Over time, the refinements in laser optics and the overall design of femtosecond laser platforms led to it becoming an essential tool for corneal surgeons. In conclusion, femtosecond laser is a heavily utilized tool in refractive and nonrefractive corneal surgical procedures, and further technological advances are likely to expand its applications. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

Regional repeatability measures of corneal thickness: Orbscan II and ultrasound.

PubMed

Jonuscheit, Sven; Doughty, Michael J

2007-01-01

To compare repeatability of the measures of corneal thickness obtained by slit-scanning light method (Orbscan II) with those obtained by an ultrasound pachymeter, with special interest in the peripheral region of the cornea. On 24 normal adults, aged 20 to 58 years (average 36 years) with up to -8.5 DS refractive error, three measures of corneal thickness were taken using Orbscan II and then by ultrasound pachymetry (under topical anesthesia with benoxinate 0.4%). The Orbscan central sample zone of 1 mm was selected, or the numerical maps were used to extract single point data along the horizontal corneal meridian to the nasal and temporal sides out to 4.5 mm. Ultrasound readings were taken from the central cornea and at the periphery just inside the limbus (4.5 mm from center) with a 2.4-mm diameter probe. For a central 1-mm diameter zone, the coefficient of variation (CV) for three consecutive corneal thickness measures was 0.81%+/-0.44%, but was marginally higher (p=0.004), if just the central single point data was taken with Orbscan (0.86%+/-0.45%). Similar repeatability was noted for the numerical output across the temporal side along the horizontal meridian out to 2.5 mm from the center, but farther out to 4 mm and on the nasal side the repeatability was slightly less and around 1.0% (p<0.001). Orbscan point readings of thickness could only sometimes be obtained at 4.5 mm temporally (with a poorer CV of 1.32%) and very rarely at 4.5 mm on the nasal side. No absolute differences in Orbscan repeatability were noted when comparing emmetropic with myopic subjects (p>or=0.5). Ultrasound pachymetry readings across the central zone were repeatable to 0.82%+/-0.67%. When measured with the edge of the ultrasound probe just touching the limbus, the repeatability of ultrasound readings was 1.37%+/-1.10% temporally and 1.49%+/-1.02% nasally, but neither was statistically worse that the most peripheral readings for Orbscan (p>or=0.210). However, it was also noted that the

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

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.

Corneal confocal microscopy following conventional, transepithelial, and accelerated corneal collagen cross-linking procedures for keratoconus.

PubMed

Touboul, David; Efron, Nathan; Smadja, David; Praud, Delphine; Malet, Florence; Colin, Joseph

2012-11-01

To compare early corneal healing following conventional, transepithelial, and accelerated corneal collagen cross-linking (CXL) protocols. Twenty-four patients with progressive keratoconus were divided into three groups to receive conventional, transepithelial, or accelerated CXL. In vivo corneal confocal microscopy was performed on each patient preoperatively and at 1, 3, and 6 months postoperatively. Closure of the epithelial wound was complete 3 days following conventional and accelerated CXL. The subbasal nerve plexus was essentially obliterated immediately following conventional and accelerated CXL, and virtually no nerve fibers had regenerated by 6 months. The anterior stroma showed significant changes 1 month following conventional CXL; these changes were similar but more pronounced following accelerated CXL. Observed stromal changes included complete obliteration of keratocytes, increased tissue reflectivity, a honeycomb-like appearance, and circular lacunae. Some recovery of keratocyte density was noted after 6 months. These changes were less pronounced in the mid-stroma, and there were no apparent changes to the posterior stroma or endothelium. The cornea appeared to be unaltered following transepithelial CXL. In vivo corneal confocal microscopy analysis of the postoperative impact of CXL on the cornea revealed clear differences among conventional, accelerated, and transepithelial CXL protocols. Accelerated CXL had a greater impact than conventional CXL on the anterior cornea, whereas transepithelial CXL did not appear to alter corneal morphology. Copyright 2012, SLACK Incorporated.

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.

AAV Gene Therapy for MPS1-associated Corneal Blindness.

PubMed

Vance, Melisa; Llanga, Telmo; Bennett, Will; Woodard, Kenton; Murlidharan, Giridhar; Chungfat, Neil; Asokan, Aravind; Gilger, Brian; Kurtzberg, Joanne; Samulski, R Jude; Hirsch, Matthew L

2016-02-22

Although cord blood transplantation has significantly extended the lifespan of mucopolysaccharidosis type 1 (MPS1) patients, over 95% manifest cornea clouding with about 50% progressing to blindness. As corneal transplants are met with high rejection rates in MPS1 children, there remains no treatment to prevent blindness or restore vision in MPS1 children. Since MPS1 is caused by mutations in idua, which encodes alpha-L-iduronidase, a gene addition strategy to prevent, and potentially reverse, MPS1-associated corneal blindness was investigated. Initially, a codon optimized idua cDNA expression cassette (opt-IDUA) was validated for IDUA production and function following adeno-associated virus (AAV) vector transduction of MPS1 patient fibroblasts. Then, an AAV serotype evaluation in human cornea explants identified an AAV8 and 9 chimeric capsid (8G9) as most efficient for transduction. AAV8G9-opt-IDUA administered to human corneas via intrastromal injection demonstrated widespread transduction, which included cells that naturally produce IDUA, and resulted in a >10-fold supraphysiological increase in IDUA activity. No significant apoptosis related to AAV vectors or IDUA was observed under any conditions in both human corneas and MPS1 patient fibroblasts. The collective preclinical data demonstrate safe and efficient IDUA delivery to human corneas, which may prevent and potentially reverse MPS1-associated cornea blindness.

AAV Gene Therapy for MPS1-associated Corneal Blindness

PubMed Central

Vance, Melisa; Llanga, Telmo; Bennett, Will; Woodard, Kenton; Murlidharan, Giridhar; Chungfat, Neil; Asokan, Aravind; Gilger, Brian; Kurtzberg, Joanne; Samulski, R. Jude; Hirsch, Matthew L.

2016-01-01

Although cord blood transplantation has significantly extended the lifespan of mucopolysaccharidosis type 1 (MPS1) patients, over 95% manifest cornea clouding with about 50% progressing to blindness. As corneal transplants are met with high rejection rates in MPS1 children, there remains no treatment to prevent blindness or restore vision in MPS1 children. Since MPS1 is caused by mutations in idua, which encodes alpha-L-iduronidase, a gene addition strategy to prevent, and potentially reverse, MPS1-associated corneal blindness was investigated. Initially, a codon optimized idua cDNA expression cassette (opt-IDUA) was validated for IDUA production and function following adeno-associated virus (AAV) vector transduction of MPS1 patient fibroblasts. Then, an AAV serotype evaluation in human cornea explants identified an AAV8 and 9 chimeric capsid (8G9) as most efficient for transduction. AAV8G9-opt-IDUA administered to human corneas via intrastromal injection demonstrated widespread transduction, which included cells that naturally produce IDUA, and resulted in a >10-fold supraphysiological increase in IDUA activity. No significant apoptosis related to AAV vectors or IDUA was observed under any conditions in both human corneas and MPS1 patient fibroblasts. The collective preclinical data demonstrate safe and efficient IDUA delivery to human corneas, which may prevent and potentially reverse MPS1-associated cornea blindness. PMID:26899286

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.

Co-culture of human bone marrow mesenchymal stem cells and macrophages attenuates lipopolysaccharide-induced inflammation in human corneal epithelial cells.

PubMed

Jeong, Won-Yong; Kim, Ji-Hye; Kim, Chan-Wha

2018-05-01

Dry eye syndrome (DES) is considered as an ocular surface inflammatory disease. Previous studies have shown inflammation plays an important role in the progression and onset of DES. Co-culture of human bone marrow mesenchymal stem cells (HBMSCs) and macrophages showed immunomodulatory effects via regulation of cytokine regulation. Thus, the aim of this study was to investigate the effect of the interaction of these cells on in vitro DES model. The conditioned media (CM) from macrophages, HBMSCs, and HBMSCs + macrophages were treated to human corneal epithelial cells, which showed significant reduction in IL-1α and IL-1β expression levels in HBMSCs + macrophages group. Moreover, the IL-1 Receptor Antagonist (IL-1RA) was highly expressed in the CM from the HBMSCs + macrophages group. Wounded eyes of mice were treated with IL-1RA at 0-100 ng/mL for 16 h, the wound size was reduced. The results of this study might lead to the identification of new therapeutic targets for DES.

Surgical management of corneal infections.

PubMed

Tuli, Sonal; Gray, Matthew

2016-07-01

The purpose of this review is to discuss the options for, and recent developments in, the surgical treatment of corneal infections. Although the mainstay of treatment of corneal infections is topical antimicrobial agents, surgical intervention may be necessary in a number of cases. These include advanced disease at presentation, resistant infections, and progressive ulceration despite appropriate treatment. Prompt and appropriate treatment can make the difference between a good outcome and loss of vision or the eye. There are a number of surgical therapies available for corneal infections. Preferred therapeutic modalities differ based on the size, causation, and location of the infection but consist of either replacement of the infected tissue or structural support of the tissue to allow healing. Although there are no completely novel therapies that have been developed recently, there have been incremental improvements in the existing treatment modalities making them more effective, easier, and safer. Several options are available for surgically managing corneal infections. Ophthalmologists should select the optimal procedure based on the individual patient's situation. http://links.lww.com/COOP/A20.

Surgical management of corneal infections

PubMed Central

Tuli, Sonal; Gray, Matthew

2016-01-01

Purpose of review The purpose of this review is to discuss the options for, and recent developments in, the surgical treatment of corneal infections. While the mainstay of treatment of corneal infections is topical antimicrobial agents, surgical intervention may be necessary in a number of cases. These include advanced disease at presentation, resistant infections, and progressive ulceration despite appropriate treatment. Prompt and appropriate treatment can make the difference between a good outcome and loss of vision or the eye. Recent findings There are a number of surgical therapies available for corneal infections. Preferred therapeutic modalities differ based on the size, causation, and location of the infection but consist of either replacement of the infected tissue or structural support of the tissue to allow healing. While there are no completely novel therapies that have been developed recently, there have been incremental improvements in the existing treatment modalities making them more effective, easier, and safer. Summary Several options are available for surgically managing corneal infections. Ophthalmologists should select the optimal procedure based on the individual patient’s situation. PMID:27096375

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.

Pharmacological activities of an eye drop containing Matricaria chamomilla and Euphrasia officinalis extracts in UVB-induced oxidative stress and inflammation of human corneal cells.

PubMed

Bigagli, Elisabetta; Cinci, Lorenzo; D'Ambrosio, Mario; Luceri, Cristina

2017-08-01

Ultraviolet B (UVB) exposure is a risk factor for corneal damage resulting in oxidative stress, inflammation and cell death. The aim of this study was to investigate the potential protective effects of a commercial eye drop (Dacriovis™) containing Matricaria chamomilla and Euphrasia officinalis extracts on human corneal epithelial cells (HCEC-12) against UVB radiation-induced oxidative stress and inflammation as well as the underlying mechanisms. The antioxidant potential of the eye drops was evaluated by measuring the ferric reducing antioxidant power and the total phenolic content by Folin-Ciocalteu reagent. HCEC-12 cells were exposed to UVB radiation and treated with the eye drops at various concentrations. Cell viability, wound healing assay, reactive oxygen species (ROS) levels, protein and lipid oxidative damage and COX-2, IL-1β, iNOS, SOD-2, HO-1 and GSS gene expression, were assessed. Eye drops were able to protect corneal epithelial cells from UVB-induced cell death and ameliorated the wound healing; the eye drops exhibited a strong antioxidant activity, decreasing ROS levels and protein and lipid oxidative damage. Eye drops also exerted anti-inflammatory activities by decreasing COX-2, IL-1β, iNOS expression, counteracted UVB-induced GSS and SOD-2 expression and restored HO-1 expression to control levels. These findings suggest that an eye drop containing Matricaria chamomilla and Euphrasia officinalis extracts exerts positive effects against UVB induced oxidative stress and inflammation and may be useful in protecting corneal epithelial cells from UVB exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

Topical non-steroidal anti-inflammatory drugs for analgesia in traumatic corneal abrasions.

PubMed

Wakai, Abel; Lawrenson, John G; Lawrenson, Annali L; Wang, Yongjun; Brown, Michael D; Quirke, Michael; Ghandour, Omar; McCormick, Ryan; Walsh, Cathal D; Amayem, Ahmed; Lang, Eddy; Harrison, Nick

2017-05-18

Traumatic corneal abrasions are relatively common and there is a lack of consensus about analgesia in their management. It is therefore important to document the clinical efficacy and safety profile of topical ophthalmic non-steroidal anti-inflammatory drugs (NSAIDs) in the management of traumatic corneal abrasions. To identify and evaluate all randomised controlled trials (RCTs) comparing the use of topical NSAIDs with placebo or any alternative analgesic interventions in adults with traumatic corneal abrasions (including corneal abrasions arising from foreign body removal), to reduce pain, and its effects on healing time. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 2), MEDLINE Ovid (1946 to 30 March 2017), Embase Ovid (1947 to 30 March 2017), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 30 March 2017), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/); searched 30 March 2017, ZETOC (1993 to 30 March 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 30 March 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 30 March 2017 and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 30 March 2017. We did not use any date or language restrictions in the electronic searches for trials.We checked the reference lists of identified trials to search for further potentially relevant studies. RCTs comparing topical NSAIDs to placebo or any alternative analgesic interventions in adults with traumatic corneal abrasions. Two review authors independently performed data extraction and assessed risks of bias in the included studies. We rated the certainty of the evidence using GRADE. We included nine studies that met the inclusion criteria, reporting data on 637 participants.The studies took place in the UK, USA, Israel, Italy

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.

Dose-response effects of corneal anesthetics.

PubMed

Polse, K A; Keener, R J; Jauregui, M J

1978-01-01

With double-masking procedures, the dose-response curves for 0.1, 0.2, and 0.4% benoxinate and 0.125, 0.25, and 0.50% proparacaine hydrochloride were determined by monitoring changes in corneal touch threshold after applying each anesthetic. The level of corneal anesthesia necessary for applanation tonometry was also determined. The maximum increase in threshold that could be measured following instillation of 50 microliter of the drug was 200 mg/mm2 All 6 anesthetic solutions produced this amount of decreased corneal sensitivity. Recovery from the anesthetic was exponential for all concentrations; however, the lower doses had the shortest duration. For applanation tonometry, the corneal threshold for touch must be 75 mg/mm2 or higher. We conclude that a quarter to a half of the commonly used anesthetic dose is sufficient for routine tonometric evaluation.

Extended Latanoprost Release from Commercial Contact Lenses: In Vitro Studies Using Corneal Models

PubMed Central

Mohammadi, Saman; Jones, Lyndon; Gorbet, Maud

2014-01-01

In this study, we compared, for the first time, the release of a 432 kDa prostaglandin analogue drug, Latanoprost, from commercially available contact lenses using in vitro models with corneal epithelial cells. Conventional polyHEMA-based and silicone hydrogel soft contact lenses were soaked in drug solution ( solution in phosphate buffered saline). The drug release from the contact lens material and its diffusion through three in vitro models was studied. The three in vitro models consisted of a polyethylene terephthalate (PET) membrane without corneal epithelial cells, a PET membrane with a monolayer of human corneal epithelial cells (HCEC), and a PET membrane with stratified HCEC. In the cell-based in vitro corneal epithelium models, a zero order release was obtained with the silicone hydrogel materials (linear for the duration of the experiment) whereby, after 48 hours, between 4 to 6 of latanoprost (an amount well within the range of the prescribed daily dose for glaucoma patients) was released. In the absence of cells, a significantly lower amount of drug, between 0.3 to 0.5 , was released, (). The difference observed in release from the hydrogel lens materials in the presence and absence of cells emphasizes the importance of using an in vitro corneal model that is more representative of the physiological conditions in the eye to more adequately characterize ophthalmic drug delivery materials. Our results demonstrate how in vitro models with corneal epithelial cells may allow better prediction of in vivo release. It also highlights the potential of drug-soaked silicone hydrogel contact lens materials for drug delivery purposes. PMID:25207851

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 injury

MedlinePlus

... as sand or dust Ultraviolet injuries: Caused by sunlight, sun lamps, snow or water reflections, or arc- ... a corneal injury if you: Are exposed to sunlight or artificial ultraviolet light for long periods of ...

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.

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...

An assessment of regional differences in corneal thickness in normal human eyes, using the Orbscan II or ultrasound pachymetry.

PubMed

Doughty, Michael J; Jonuscheit, Sven

2007-04-01

In recent years, there has been increasing interest in the characteristics of the peripheral cornea close to the limbus, in both tonometry measures and refractive surgery, but there is relatively little information on these characteristics as provided by modern day pachymetry instruments such as the Orbscan (Bausch & Lomb, Rochester, New York). The current study was therefore undertaken to assess the corneal thickness profile along the horizontal meridian by this scanning slit light method, comparing the data with that obtained with an ultrasound pachymeter. Noncontact specular microscopy was first performed on 17 adults (aged between 20 and 64 years) to check that the corneas were normal. Then, 3 assessments of the corneal thickness profile across the horizontal meridian were taken using the Orbscan II, and both the regional map data (7-mm-diameter measurement ring, 1-mm sample zones) and the point data from the numerical pachymetry output were used to extract data at specific locations nominally 0.5 mm apart. Ultrasound pachymetry (under topical anesthesia with benoxinate 0.4%) was then used to obtain thickness values at central, mid-peripheral (2.75 mm), and peripheral locations close to the limbus (4.5 mm). Specular microscopy yielded mean thickness of 0.529 +/- 0.032 mm, whereas single-point Orbscan readings at the geometric center of the cornea averaged 0.579 +/- 0.037 mm. Orbscan readings around the 7-mm-diameter measurement zone along the horizontal meridian averaged 0.681 +/- 0.034 mm (i.e., were 0.101 mm or 17.6% greater; P < 0.001). Mid-peripheral readings taken from the numerical maps at 2.5 to 3.0 mm averaged 0.645 mm (or 11% higher than central point readings), whereas peripheral readings between 4.0 and 4.5 mm averaged 0.727 mm (i.e., 26% higher than central point values). In marked contrast, ultrasound readings in the mid-periphery (2.75 mm) averaged just 0.553 mm (or 5.5% greater than the central corneal thickness [CCT]) and just 0.612 mm (i.e., 16

N-Acetylcysteine increases corneal endothelial cell survival in a mouse model of Fuchs endothelial corneal dystrophy.

PubMed

Kim, Eun Chul; Meng, Huan; Jun, Albert S

2014-10-01

The present study evaluated survival effects of N-acetylcysteine (NAC) on cultured corneal endothelial cells exposed to oxidative and endoplasmic reticulum (ER) stress and in a mouse model of early-onset Fuchs endothelial corneal dystrophy (FECD). Cultured bovine corneal endothelial cell viability against oxidative and ER stress was determined by CellTiter-Glo(®) luminescent reagent. Two-month-old homozygous knock-in Col8a2(L450W/L450W) mutant (L450W) and C57/Bl6 wild-type (WT) animals were divided into two groups of 15 mice. Group I received 7 mg/mL NAC in drinking water and Group II received control water for 7 months. Endothelial cell density and morphology were evaluated with confocal microscopy. Antioxidant gene (iNos) and ER stress/unfolded protein response gene (Grp78 and Chop) mRNA levels and protein expression were measured in corneal endothelium by real time PCR and Western blotting. Cell viability of H2O2 and thapsigargin exposed cells pre-treated with NAC was significantly increased compared to untreated controls (p < 0.01). Corneal endothelial cell density (CD) was higher (p = 0.001) and percent polymegathism was lower (p = 0.04) in NAC treated L450W mice than in untreated L450W mice. NAC treated L450W endothelium showed significant upregulation of iNos, whereas Grp78 and Chop were downregulated compared to untreated L450W endothelium by real time PCR and Western blotting. NAC increases survival in cultured corneal endothelial cells exposed against ER and oxidative stress. Systemic NAC ingestion increases corneal endothelial cell survival which is associated with increased antioxidant and decreased ER stress markers in a mouse model of early-onset FECD. Our study presents in vivo evidence of a novel potential medical treatment for FECD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Crystalline Subtype of Pre-Descemetic Corneal Dystrophy

PubMed Central

Dolz-Marco, Rosa; Gallego-Pinazo, Roberto; Pinazo-Durán, María Dolores; Díaz-Llopis, Manuel

2014-01-01

Purpose To report corneal findings in a familial case of the crystalline subtype of pre-Descemetic corneal dystrophy. Case Report A 19-year-old girl and her 44-year-old mother were found to have asymptomatic, bilateral, punctiform and multi-colored crystalline opacities across the whole posterior layer of the corneas. Endothelial specular microscopy revealed the presence of white round flecks located at different levels anterior to the endothelium. No systemic abnormalities or medications could be related to account for these findings. Conclusion To the best of our knowledge, this is the third familial report of this rare corneal disorder. Differential diagnosis may include Schnyder corneal dystrophy, cystinosis, Bietti´s dystrophy and monoclonal gammopathy. PMID:25279130

Long-term cultivation of human corneal endothelial cells by telomerase expression.

PubMed

Liu, Zhiping; Zhuang, Jing; Li, Chaoyang; Wan, Pengxia; Li, Naiyang; Zhou, Qiang; Zhou, Chenjing; Huang, Zheqian; Wang, Zhichong

2012-07-01

The objective of this study was to explore the potential role of human telomerase reverse transcriptase (TERT) in extending the proliferative lifespan of human corneal endothelial cells (HCECs) under long-term cultivation. A primary culture was initiated with a pure population of HCECs in DMEM/F12 media containing 10% fetal bovine serum and other various supplements. TERT gene was successfully transfected into normal HCECs. A stable HCECs cell line (TERT-HCECs) that expressed TERT was established. The cells could be subcultured for 36 passages. Within this line of cells, TERT not only extended proliferative lifespan and inhibited apoptosis but also enhanced the cell line remaining the normal characteristics similar to HCECs. There were no significantly differences in the expression of the pump function related proteins voltage dependent anion channel 3 (VDAC3), sodium bicarbonate cotransporter member 4 (SLC4A4), chloride channel protein 3 (CLCN3), Na(+)/K(+)-ATPase α1, and ZO-1 in the cell line TERT-HCECs and primary HCECs. TERT-HCECs formed a monolayer cell sheet, maintained similar cell junction formation and pump function with primary HCECs. Karyotype analysis exhibited normal chromosomal numbers. The soft agar colony assay and tumor formation in nude mice assay showed no malignant alterations in TERT-HCECs. Our findings indicated that we had established a cell line with its similar phenotype and properties to primary HCECs. Further study of the TERT-HCECs may be valuable in studying the function of the cells in vivo. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

Anti-inflammatory effect of topical administration of tofacitinib on corneal inflammation.

PubMed

Sakimoto, Tohru; Ishimori, Akiko

2016-04-01

We evaluated an anti-inflammatory effect of topical administration of tofacitinib, janus kinase (JAK) blocker, on corneal inflammation. Topical instillation of either tofacitinib or PBS was applied after wounding BALB/c mice corneas with alkali burn. Topical instillation was performed until day 14 after injury and injured eye was analyzed. The vascularized area in the alkali burned cornea was significantly reduced in the tofacitinib group compared with that in the PBS group. The immunoreactivity of Gr-1, F4/80, IFN-γ, and phosphorylated STAT(signal transducer and activator of transcription)1 in corneal stroma was diminished significantly in the tofacitinib group. Using laser capture microdissection system and quantitative PCR array analysis, the expression levels of CXCL9, CXCL5, CCL7, CCL2, MMP(matrix metalloproteinase)-9, and STAT1 in corneal stroma were down-regulated in the tofacitinib group. In in vitro study, human fibroblast pretreated by IFN-γ showed phosphorylation of STAT1, and this phosphorylation was down-regulated by adding tofacitinib to the culture medium. These results indicate the topical application of JAK inhibitor causes down-regulation of JAK- or IFN-γ-related molecules. Therefore, we deduce that application of JAK inhibitor for topical instillation may contribute to the treatment of corneal inflammation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Corneal biomechanical properties in floppy eyelid syndrome.

PubMed

Muniesa, MaJesús; Muniesa Royo, MaJesús; March, Ana; March de Ribot, Ana; Sánchez-de-la-Torre, Manuel; Huerva, Valetín; Huerva Escanilla, Valetín; Jurjo, Carmen; Jurjo Campo, Carmen; Barbé, Ferran; Barbé Illa, Ferran

2015-05-01

To determine corneal biomechanical properties in patients with floppy eyelid syndrome (FES) and to compare them with eyes of controls. This case-control study included 208 eyes (72 eyes with FES and 136 without FES) of 107 patients (37 patients with FES and 70 without FES). Patients underwent a complete clinical eye examination that included corneal biomechanical evaluation carried out with the Reichert Ocular Response Analyzer. Corneal hysteresis (CH), corneal resistance factor (CRF), central corneal thickness (CCT), Goldmann-correlated intraocular pressure (IOPg), and corneal-compensated intraocular pressure (IOPcc) were evaluated. Mean CH was significantly lower in patients with FES than in those without FES (9.51 ± 1.56 vs. 11.66 ± 9.11; P < 0.001). These results remained statistically significant after adjusting for age and apnea-hypoapnea index (AHI) (P = 0.028). Mean CRF was 10.02 ± 2.08 in the group of patients with FES and 11.21 ± 5.36 in the group of patients without FES (P = 0.001). Mean IOPcc was 17.7 ± 4.8 in patients with FES and 16.3 ± 4.4 in those without FES (P = 0.036). After adjusting for age and AHI, these differences in CRF and IOPcc were not statistically significant (P = 0.26 and P = 0.87, respectively). No statistically significant difference was found between patients with and without FES for Goldmann-correlated intraocular pressure or CCT. Patients with FES had statistically lower CH values. Our findings suggest that corneal biomechanical properties could be changed in patients with FES, reflecting additional structural changes in FES.

Gastric pentadecapeptide BPC 157 promotes corneal epithelial defects healing in rats.

PubMed

Lazić, Ratimir; Gabrić, Nikica; Dekaris, Iva; Bosnar, Damir; Boban-Blagaić, Alenka; Sikirić, Predrag

2005-06-01

We evaluated the role of human gastric pentadecapeptide BPC 157 in corneal epithelial defects healing in rats. 48 rats, in 4 groups (N=12). Total debridement of corneal epithelium preformed unilaterally and lesions stained and photographed. Animals medicated as follows: distilled water (control group) or BPC 157 2 pg/ml, 2 ng/ml, 2 microg/ml, 2 drops/rat eye started immediately after injury induction, every 8 hours up to 40 hours (i.e., at 0, 8, 16, 24, 32, 40 h). Lesions were photographed before application or sacrifice (at 48 h). Defect area was analyzed using a special program. Through 48 hour period a steady recovery is noted in controls. Recovery was markedly accelerated in eyes on microg- or ng-topical regimen of BPC 157 (p < 0.05). Of note, unlike control lesion present also after 48 h, these lesions disappeared already following 40 h (microg) or 48 h (ng) post-injury. BPC 157 was shown to be effective in promoting corneal defects healing in rats. Results were dose dependent.

Alloimmunity and Tolerance in Corneal Transplantation.

PubMed

Amouzegar, Afsaneh; Chauhan, Sunil K; Dana, Reza

2016-05-15

Corneal transplantation is one of the most prevalent and successful forms of solid tissue transplantation. Despite favorable outcomes, immune-mediated graft rejection remains the major cause of corneal allograft failure. Although low-risk graft recipients with uninflamed graft beds enjoy a success rate ∼90%, the rejection rates in inflamed graft beds or high-risk recipients often exceed 50%, despite maximal immune suppression. In this review, we discuss the critical facets of corneal alloimmunity, including immune and angiogenic privilege, mechanisms of allosensitization, cellular and molecular mediators of graft rejection, and allotolerance induction. Copyright © 2016 by The American Association of Immunologists, Inc.

Corneal endothelial dysfunction in Pearson syndrome.

PubMed

Kasbekar, Shivani A; Gonzalez-Martin, Jose A; Shafiq, Ayad E; Chandna, Arvind; Willoughby, Colin E

2013-01-01

Mitochondrial disorders are associated with well recognized ocular manifestations. Pearson syndrome is an often fatal, multisystem, mitochondrial disorder that causes variable bone marrow, hepatic, renal and pancreatic exocrine dysfunction. Phenotypic progression of ocular disease in a 12-year-old male with Pearson syndrome is described. This case illustrates phenotypic drift from Pearson syndrome to Kearns-Sayre syndrome given the patient's longevity. Persistent corneal endothelial failure was noted in addition to ptosis, chronic external ophthalmoplegia and mid-peripheral pigmentary retinopathy. We propose that corneal edema resulting from corneal endothelial metabolic pump failure occurs within a spectrum of mitochondrial disorders.

Aniridia-related keratopathy: Structural changes in naïve and transplanted corneal buttons.

PubMed

Vicente, André; Byström, Berit; Lindström, Mona; Stenevi, Ulf; Pedrosa Domellöf, Fátima

2018-01-01

To study structural changes in naïve and surgically treated corneas of aniridia patients with advanced aniridia-related keratopathy (ARK). Two naïve corneal buttons from patients with advanced ARK submitted to penetrating keratoplasty for the first time, one corneal button from an ARK patient that had undergone a keratolimbal allograft (KLAL), two corneal buttons from ARK patients who had previously undergone centered or decentered transplantation and were now retransplanted and two adult healthy donor control corneas were processed for immunohistochemistry. Antibodies against extracellular matrix components in the stroma and in the epithelial basement membrane (collagen I and IV, collagen receptor α11 integrin and laminin α3 chain), markers of fibrosis, wound healing and vascularization (fibronectin, tenascin-C, vimentin, α-SMA and caveolin-1), cell division (Ki-67) and macrophages (CD68) were used. Naïve ARK, KLAL ARK corneas and transplanted corneal buttons presented similar histopathological changes with irregular epithelium and disruption or absence of epithelial basal membrane. There was a loss of the orderly pattern of collagen lamellae and absence of collagen I in all ARK corneas. Vascularization was revealed by the presence of caveolin-1 and collagen IV in the pannus of all ARK aniridia corneas. The changes observed in decentered and centered transplants were analogous. Given the similar pathological features of all cases, conditions inherent to the host seem to play an important role on the pathophysiology of the ARK in the long run.

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

Posterior corneal astigmatism in refractive lens exchange surgery.

PubMed

Rydström, Elin; Westin, Oscar; Koskela, Timo; Behndig, Anders

2016-05-01

To assess the anterior, posterior and total corneal spherical and astigmatic powers in patients undergoing refractive lens exchange (RLE) surgery. In 402 consecutive patients planned for RLE at Koskelas Eye Clinic, Luleå, Sweden, right eye data from pre- and postoperative subjective refraction, preoperative IOLMaster(®) biometry and Pentacam HR(®) measurements were collected. Postoperative Pentacam HR(®) data were collected for 54 of the patients. The spherical and astigmatic powers of the anterior and posterior corneal surfaces and for the total cornea were assessed and compared, and surgically, induced astigmatism was calculated using vector analysis. The spherical power of the anterior corneal surface was 48.18 ± 1.69D with an astigmatic power of 0.83 ± 0.54D. The corresponding values for the posterior surface were -6.05 ± 2,52D and 0.26 ± 0.15D, respectively. The total corneal spherical power calculated with ray tracing was 42.47 ± 2.89D with a 0.72 ± 0.48D astigmatic power, and the corresponding figures obtained by estimating the posterior corneal surface were 43.25 ± 1.51D (p < 0.001) with a 0.75 ± 0.49D astigmatic power (p = 0.003). In eyes with anterior astigmatism with-the-rule, the total corneal astigmatism is overestimated if the posterior corneal surface is estimated; in eyes, with against-the-rule astigmatism it is underestimated. Had the posterior corneal surface been measured in this material, 14.7% of the patients would have received a spheric instead of a toric IOL, or vice versa. Estimating the posterior corneal surface in RLE patients leads to systematic measurement errors that can be reduced by measuring the posterior surface. Such an approach can potentially increase the refractive outcome accuracy in RLE surgery. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Rapid tissue engineering of biomimetic human corneal limbal crypts with 3D niche architecture.

PubMed

Levis, Hannah J; Massie, Isobel; Dziasko, Marc A; Kaasi, Andreas; Daniels, Julie T

2013-11-01

Limbal epithelial stem cells are responsible for the maintenance of the human corneal epithelium and these cells reside in a specialised stem cell niche. They are located at the base of limbal crypts, in a physically protected microenvironment in close proximity to a variety of neighbouring niche cells. Design and recreation of elements of various stem cell niches have allowed researchers to simplify aspects of these complex microenvironments for further study in vitro. We have developed a method to rapidly and reproducibly create bioengineered limbal crypts (BLCs) in a collagen construct using a simple one-step method. Liquid is removed from collagen hydrogels using hydrophilic porous absorbers (HPAs) that have custom moulded micro-ridges on the base. The resulting topography on the surface of the thin collagen constructs resembles the dimensions of the stromal crypts of the human limbus. Human limbal epithelial cells seeded onto the surface of the constructs populate these BLCs and form numerous layers with a high proportion of the cells lining the crypts expressing putative stem cell marker, p63α. The HPAs are produced using a moulding process that is flexible and can be adapted depending on the requirements of the end user. Creation of defined topographical features using this process could be applicable to numerous tissue-engineering applications where varied 3-dimensional niche architectures are required. Copyright © 2013 Elsevier Ltd. All rights reserved.

Confocal microscopy evaluation of stromal fluorescence intensity after standard and accelerated iontophoresis-assisted corneal cross-linking.

PubMed

Lanzini, Manuela; Curcio, Claudia; Spoerl, Eberhard; Calienno, Roberta; Mastropasqua, Alessandra; Colasante, Martina; Mastropasqua, Rodolfo; Nubile, Mario; Mastropasqua, Leonardo

2017-02-01

The aim of this study is to determine modifications in stromal fluorescence intensity after different corneal cross-linking (CXL) procedures and to correlate stromal fluorescence to corneal biomechanical resistance. For confocal microscopy study, 15 human cadaver corneas were examined. Three served as control (group 1), three were just soaked with iontophoresis procedure (group 2), three were treated with standard epi-off technique (group 3), and six underwent iontophoresis imbibition. Three of later six were irradiated for 30 min with 3 mW/cm 2 UVA (group 4) and three for 9 min at 10 mW/cm 2 UVA (group 5). Confocal microscopy was performed to quantify the fluorescence intensity in the cornea at different stromal depths. For biomechanical study, 30 human cadaver corneas were randomly divided into five groups and treated as previously described. Static stress-strain measurements of the corneas were performed. Iontophoresis imbibition followed by 10mW/cm 2 irradiation proved to increase stromal fluorescence into the corneal stroma and significant differences were revealed between group 3 and 5 both at 100 (p = 0.0171) and 250 µm (p = 0.0024), respectively. Biomechanical analysis showed an improvement of corneal resistance in group 5. Iontophoresis imbibition followed by accelerated irradiation increased the stromal fluorescence and is related to an improvement of biomechanical resistance. This approach may represent a new strategy to achieve greater concentrations of riboflavin without removing corneal epithelium and improve clinical results while reducing the side effects of CXL.

A novel explanation of corneal clouding in a bone marrow transplant-treated patient with Hurler syndrome

PubMed Central

Yuan, Ching; Bothun, Erick D.; Hardten, David R.; Tolar, Jakub; McLoon, Linda K.

2016-01-01

One common complication of mucopolysaccharidosis I-Hurler (MPS1-H) is corneal clouding, which occurs despite current treatments, including bone marrow transplantation. Human corneas were obtained from a 14 year old subject with MPS1-H and visual disability from progressive corneal clouding despite a prior bone marrow transplant at age 2. This was compared to a cornea from a 17 year old donated to our eye bank after his accidental death. The corneas were analyzed microscopically after staining with Alcian blue, antibodies to collagen I, IV, VI, and α-smooth muscle actin. Differences in levels of expression of the indicated molecules were assessed. Corneas from Hurler and control mice were examined similarly to determine potential mechanistic overlap. The MPS1-H subject cornea showed elevations in mucopolysaccharide deposition. The MPS1-H and Hurler mice corneas showed increased and disorganized expression of collagen I and IV relative to the control corneas. The MPS1-H corneas also showed increased and disordered expression of collagen VI. Positive expression of α-smooth muscle actin indicated myofibroblast conversion within the MPS1-H cornea in both the patient and mutant mouse material compared to normal human and control mouse cornea. Increased deposition of collagens and smooth muscle actin correlate with corneal clouding, providing a potential mechanism for corneal clouding despite bone marrow transplantation in MPS1-H patients. It might be possible to prevent or slow the onset of corneal clouding by treating the cornea with drugs known to prevent myofibroblast conversion. PMID:27235795

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.

Depth-Dependent Transverse Shear Properties of the Human Corneal Stroma

PubMed Central

Petsche, Steven J.; Chernyak, Dimitri; Martiz, Jaime; Levenston, Marc E.

2012-01-01

Purpose. To measure the transverse shear modulus of the human corneal stroma and its profile through the depth by mechanical testing, and to assess the validity of the hypothesis that the shear modulus will be greater in the anterior third due to increased interweaving of lamellae. Methods. Torsional rheometry was used to measure the transverse shear properties of 6 mm diameter buttons of matched human cadaver cornea pairs. One cornea from each pair was cut into thirds through the thickness with a femtosecond laser and each stromal third was tested individually. The remaining intact corneas were tested to measure full stroma shear modulus. The shear modulus from a 1% shear strain oscillatory test was measured at various levels of axial compression for all samples. Results. After controlling for axial compression, the transverse shear moduli of isolated anterior layers were significantly higher than central and posterior layers. Mean modulus values at 0% axial strain were 7.71 ± 6.34 kPa in the anterior, 1.99 ± 0.45 kPa in the center, 1.31 ± 1.01 kPa in the posterior, and 9.48 ± 2.92 kPa for full thickness samples. A mean equilibrium compressive modulus of 38.7 ± 8.6 kPa at 0% axial strain was calculated from axial compression measured during the shear tests. Conclusions. Transverse shear moduli are two to three orders of magnitude lower than tensile moduli reported in the literature. The profile of shear moduli through the depth displayed a significant increase from posterior to anterior. This gradient supports the hypothesis and corresponds to the gradient of interwoven lamellae seen in imaging of stromal cross-sections. PMID:22205608

Microspectroscopy of spectral biomarkers associated with human corneal stem cells

PubMed Central

Nakamura, Takahiro; Kelly, Jemma G.; Trevisan, Júlio; Cooper, Leanne J.; Bentley, Adam J.; Carmichael, Paul L.; Scott, Andrew D.; Cotte, Marine; Susini, Jean; Martin-Hirsch, Pierre L.; Kinoshita, Shigeru; Martin, Francis L.

2010-01-01

Purpose Synchrotron-based radiation (SRS) Fourier-transform infrared (FTIR) microspectroscopy potentially provides novel biomarkers of the cell differentiation process. Because such imaging gives a “biochemical-cell fingerprint” through a cell-sized aperture, we set out to determine whether distinguishing chemical entities associated with putative stem cells (SCs), transit-amplifying (TA) cells, or terminally-differentiated (TD) cells could be identified in human corneal epithelium. Methods Desiccated cryosections (10 μm thick) of cornea on barium fluoride infrared transparent windows were interrogated using SRS FTIR microspectroscopy. Infrared analysis was performed through the acquisition of point spectra or image maps. Results Point spectra were subjected to principal component analysis (PCA) to identify distinguishing chemical entities. Spectral image maps to highlight SCs, TA cells, and TD cells of the cornea were then generated. Point spectrum analysis using PCA highlighted remarkable segregation between the three cell classes. Discriminating chemical entities were associated with several spectral differences over the DNA/RNA (1,425–900 cm−1) and protein/lipid (1,800–1480 cm−1) regions. Prominent biomarkers of SCs compared to TA cells and/or TD cells were 1,040 cm−1, 1,080 cm−1, 1,107 cm−1, 1,225 cm−1, 1,400 cm−1, 1,525 cm−1, 1,558 cm−1, and 1,728 cm−1. Chemical entities associated with DNA/RNA conformation (1,080 cm−1 and 1,225 cm−1) were associated with SCs, whereas protein/lipid biochemicals (1,558 cm−1 and 1,728 cm−1) most distinguished TA cells and TD cells. Conclusions SRS FTIR microspectroscopy can be employed to identify differential spectral biomarkers of SCs, TA cells, and/or TD cells in human cornea. This nondestructive imaging technology is a novel approach to characterizing SCs in situ. PMID:20520745

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.

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.

Metaherpetic corneal disease in a dog associated with partial limbal stem cell deficiency and neurotrophic keratitis.

PubMed

Ledbetter, Eric C; Marfurt, Carl F; Dubielzig, Richard R

2013-07-01

To describe clinical, in vivo confocal microscopic, histopathologic, and immunohistochemical features of a dog with metaherpetic corneal disease that developed subsequent to a protracted episode of canine herpesvirus-1 (CHV-1) dendritic ulcerative keratitis. A 7-year-old, spayed-female, Miniature Schnauzer was treated for bilateral CHV-1 dendritic ulcerative keratitis. Following resolution of ulcerative keratitis, sectoral peripheral superficial corneal gray opacification, vascularization, and pigmentation slowly migrated centripetally to the axial cornea of both eyes. Corneal sensitivity measured with a Cochet-Bonnet esthesiometer was dramatically and persistently reduced. In vivo corneal confocal microscopic examination revealed regions of epithelium with a conjunctival phenotype. In these areas, the surface epithelium was thin, disorganized, and composed of hyper-reflective epithelial cells. Goblet cells and Langerhans cells were frequent, and the subbasal nerve plexus was completely absent or markedly diminished. Histopathologic abnormalities in the globes were restricted to the superficial cornea and included sectoral corneal conjunctivalization, increased anterior stromal spindle cells, and vascularization. Immunohistochemical evaluation of the corneas with anti-neurotublin antibody demonstrated attenuation of the epithelial and subbasal nerve plexuses with marked stromal hyperinnervation and increased numbers of morphologically abnormal neurites. Similar to herpes simplex virus keratitis in humans, CHV-1 ulcerative keratitis may be associated with the development of chronic degenerative corneal disease in dogs. In the described dog, this chronic corneal disease included progressive corneal opacification because of partial limbal stem cell deficiency and neurotrophic keratitis. Long-term monitoring of dogs following resolution of active CHV-1 keratitis may be indicated, particularly when ulcerations persist for an extended period. © 2012 American College of

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.

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

Primary central corneal hemangiosarcoma in a dog.

PubMed

Haeussler, David J; Rodríguez, Laura Muñoz; Wilkie, David A; Premanandan, Chris

2011-03-01

To report a case of primary central corneal hemangiosarcoma in the dog. An 11-year-old, neutered, female, German shepherd mixed breed dog was referred to the Hospital Veterinario Sierra de Madrid (Spain) for evaluation of an enlarging corneal mass of the left eye (OS). The dog was predominantly housed outdoors and was diagnosed with a history of chronic superficial keratitis of both eyes (OU) by the referring veterinarian. The corneal mass was resected by routine superficial keratectomy and submitted for histopathology and Factor VIII immunohistochemical staining. The mass was diagnosed as a corneal hemangiosarcoma with complete excision. Postoperatively, the keratectomy site healed without complication and there was no evidence of recurrence three and a half months postoperatively. Complete systemic evaluation, including abdominal ultrasound and CT scan of the head and thorax, indicated no other detectable neoplasia in the dog. Outdoor housing and ultraviolet exposure, breed, and chronic superficial keratitis were all suspected as contributing factors to the development of a primary corneal hemangiosarcoma. Surgical removal and postoperative treatment for chronic superficial keratitis provided effective therapy. © 2011 American College of Veterinary Ophthalmologists.

Central and peripheral corneal thinning in keratoconus.

PubMed

Brautaset, Rune L; Nilsson, Maria; Miller, William L; Leach, Norman E; Tukler, Johanna H; Bergmanson, Jan P G

2013-03-01

Recent data regarding the mid-peripheral portion of the removed corneal button in transplant surgery indicate histopathologically that keratoconus was present also in the peripheral portion of the button. The intent of this study was therefore to investigate if peripheral changes could also be detected clinically by measuring the central and peripheral corneal thickness of KC patients. Corneal pachymetry was measured with the Visante optical coherence tomography and Orbscan II. Of 52 subjects, 26 were KC subjects and 26 were age- and sex-matched control subjects. Corneal thickness, in KC patients, was significantly reduced in all areas compared with corneal thickness among controls with both the Visante optical coherence tomography and Orbscan II. The results of the present study have provided clinical evidence that KC is a disease affecting a wider area of the cornea. Although the KC cornea shows the greatest change in thickness in the ectatic region, this attenuation declines toward the periphery. The presence of peripheral thinning indicated that KC may be a "pancorneal" pathology and not limited to the ectatic portion.

Corneal ulceration following measles in Nigerian children.

PubMed Central

Sandford-Smith, J H; Whittle, H C

1979-01-01

Acute corneal ulceration in malnourished children is the commonest cause of childhood blindness in Northern Nigeria and usually develops after measles. Other severe diseases in malnourished children rarely precipitate corneal ulceration. A survey in a school for blind children showed that 69% of the children were blind from corneal disease, and a survey of children with corneal scars showed that at least 42% were caused by ulceration after measles. The clinical appearance of the active ulcers was very varied. The serum retinol-binding protein and prealbumin levels in children with corneal ulcers following measles were below normal, but a group of malnourished children without eye complaints following measles were found to have even lower levels. Thus a specific deficiency of vitamin A does not appear to be the primary cause of these ulcers, though it may be a contributory one. A specific measles keratitis and secondary herpes simplex infectious may be local factors contributing to this ulceration, and there is nearly always a background of protein calorie malnutrition. Racial factors may also be of some significance. PMID:508686

Treatment Results of Corneal Collagen Cross-Linking Combined with Riboflavin and 440 Nm Blue Light for Bacterial Corneal Ulcer in Rabbits.

PubMed

Wei, Shufang; Zhang, Cuiying; Zhang, Shaoru; Xu, Yanyun; Mu, Guoying

2017-10-01

To study the treatment effect of corneal collagen cross-linking (CXL) combined with 440 nm blue light and riboflavin on bacterial corneal ulcer using animal experiments. A total of 21 New Zealand white rabbits that developed Staphylococcus aureus corneal ulcer were randomly divided into three groups. Seven rabbits were used as blank control groups; seven rabbits were treated with CXL combined with riboflavin and 440 nm blue light; and seven rabbits were treated with CXL combined with riboflavin and 370 nm ultraviolet A light. Necrotic tissues or secretions from the ulcer surface, eye secretions, conjunctival hyperemia, hypopyon, corneal infiltration, and pathological changes of the cornea were all observed. The 1st, 3th, and 7th day after CXL treatment, a statistically significant difference was found among the inflammation scores of the three groups. The scores of 440 and 370 groups decreased gradually, significantly lower than that of the control group. Bacterial cultures of 440 and 370 groups turned to be negative while that of the control group remained positive. After 1 day of CXL treatment, pathology pictures of the three groups all showed loss of corneal epithelia with many inflammatory cells in deep stroma. After 7 days of CXL treatment, abscess formed in almost all corneal area in the control group, while in 440 and 370 groups, multilayer healing of corneal epithelia, neovascularization, and many inflammatory cells within ulcers and proliferation of a small amount of fibroblast were seen. CXL combined with riboflavin and 440 nm blue light is effective in treating S. aureus corneal ulcer.

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

Anti-neovascular effect of chondrocyte-derived extracellular matrix on corneal alkaline burns in rabbits.

PubMed

Lee, Hye Sook; Lee, Ji Hyun; Kim, Chae Eun; Yang, Jae Wook

2014-06-01

We investigated the effect of a chondrocyte-derived extracellular matrix (CDECM) on experimental corneal alkaline burns in rabbits. Corneal neovascularization (NV) was induced by applying an 8-mm filter paper soaked in 1 N NaOH to the right central corneas of rabbits for 1 minute. Ten days later, the rabbits were randomly divided into three groups: the alkaline burn group, the CDECM transplantation group, and the human amniotic membrane (HAM) transplantation group. The left eyes were used as controls. CDECM and HAM were transplanted onto the corneal surface to completely cover the resected area and were subsequently sutured. On the 10th day after transplantation, the structural changes of the cornea were analyzed histologically. We examined the effects of CDECM on clinical NV features and on the expression of corneal NV markers. The alkaline burn produced significant NV and increased the corneal thickness. On day 10 after transplantation, the thickness, NV and opacity of the cornea were markedly decreased in the CDECM group (p < 0.001). However, the HAM transplantation group did not exhibit improvements in these clinical parameters, and there were no significant differences relative to the burn group. In addition, the use of CDECM improved the healing of the cornea following the alkaline burn by disrupting the corneal epithelial proliferation and reducing the fibrotic changes of the stroma. The hallmarks of NV were significantly induced in the subepithelium by the alkaline burn, and these levels were also suppressed by CDECM. The CDECM suppressed corneal NV by inhibiting nuclear factor-kappa B (NF-κB) activation by blocking the PKC and Akt signaling pathways. CDECM transplantation was markedly effective in healing alkali-burned corneas by modulating the translocation of NF-κB to the nucleus, thereby representing a promising material for the noninvasive treatment of ocular surface disease.

Corneal reepithelialization and anti-inflammatory agents.

PubMed Central

Srinivasan, B D

1982-01-01

These studies have demonstrated that nonsteroidal anti-inflammatory agents (cyclooxygenase and lipoxygenase inhibitors) can inhibit PMN arrival in the tear fluid following corneal injury but do not inhibit the reepithelialization either by corneal epithelial cells or by conjunctival epithelial cells. Therefore, they can be used safely in ocular inflammatory conditions even when corneal epithelial defects are present. Corticosteroids, on the other hand, inhibit reepithelialization by conjunctival epithelial cells and not by corneal epithelial cells in the doses tested. This inhibition does not occur with pretreatment prior to injury, suggesting that corticosteroids can be used clinically in conditions that have intact corneal epithelium without fear of slowing down wound healing should epithelial defects occur when not on steroid therapy. Furthermore, the steroid inhibition is temporary since there is a breakthrough in steroid inhibition with time, and occurs only if the steroids have been used shortly after deepithelialization. The steroid inhibition can be reversed by specific steroid antagonist, indicating that the steroid effect is mediated through specific receptors. An exciting and new hypothesis proposes that corticosteroids induce the formation of an inhibitory protein that inhibits the phospholipase enzyme to cause a block in arachidonic acid release from cell membranes. This mechanism of action may also be prevalent in the steroid effect on corneal reepithelialization, and experiments are under way to isolate this inhibitory protein from steroid-treated conjunctival epithelium. This isolation and pharmacologic characterization of this inhibitory protein is of obvious advantage to the field of ophthalmic therapeutics since this protein may have the anti-inflammatory potential of the steroids without their steroid sideeffects. Images FIGURE 3 a FIGURE 3 b PMID:6763806

Corneal topography with an aberrometry-topography system.

PubMed

Mülhaupt, Michael; Dietzko, Sven; Wolffsohn, James; Bandlitz, Stefan

2018-05-07

To investigate the agreement between the central corneal radii and corneal eccentricity measurements generated by the new Wave Analyzer 700 Medica (WAV) compared to the Keratograph 4 (KER) and to test the repeatability of the instruments. 20 subjects (10 male, mean age 29.1 years, range 21-50 years) were recruited from the students and staff of the Cologne School of Optometry. Central corneal radii for the flat (r c/fl ) and steep (r c/st ) meridian as well as corneal eccentricity for the nasal (e nas ), temporal (e temp ), inferior (e inf ) and superior (e sup ) directions were measured using WAV and KER by one examiner in a randomized order. Central radii of the flat (r c/fl ) and steep (r c/st ) meridian measured with both instruments were statically significantly correlated (r = 0.945 and r = 0.951; p < 0.001). Comparison between the WAV and KER showed that r c/fl and r c/st measured with WAV were significantly steeper than those measured with KER (p < 0.001). Corneal eccentricities were statistically significantly correlated in all meridians (p < 0.05). Compared to KER, e temp and e sup measured with WAV were greater (p < 0.05), while there were no statistically significant differences for e nas and e inf (p = 0.350 and p = 0.083). For the central radii, repeated measurements were not significantly different for the KER or WAV (p > 0.05). Limits of agreement (LoA) indicate a better repeatability for the KER compared to WAV. Corneal topography measurements captured with the WAV were strongly correlated with the KER. However, due to the differences in measured corneal radii and eccentricities, the devices cannot be used interchangeably. For corneal topography the KER demonstrated better repeatability. Copyright © 2018 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Corneal wound healing promoted by 3 blood derivatives: an in vitro and in vivo comparative study.

PubMed

Freire, Vanesa; Andollo, Noelia; Etxebarria, Jaime; Hernáez-Moya, Raquel; Durán, Juan A; Morales, María-Celia

2014-06-01

The aim of this study was to compare the effect on corneal wound healing of 3 differently manufactured blood derivatives [autologous serum (AS), platelet-rich plasma, and serum derived from plasma rich in growth factors (s-PRGF)]. Scratch wound-healing assays were performed on rabbit primary corneal epithelial cultures and human corneal epithelial cells. Additionally, mechanical debridement of rabbit corneal epithelium was performed. Wound-healing progression was assessed by measuring the denuded areas remaining over time after treatment with each of the 3 blood derivatives or a control treatment. In vitro data show statistically significant differences in the healing process with all the derivatives compared with the control, but 2 of them (AS and s-PRGF) induced markedly faster wound healing. In contrast, although the mean time required to complete in vivo reepithelization was similar to that of AS and s-PRGF treatment, only wounds treated with s-PRGF were significantly smaller in size from 2.5 days onward with respect to the control treatment. All 3 blood derivatives studied are promoters of corneal reepithelization. However, the corneal wound-healing progresses differently with each derivative, being faster in vitro under AS and s-PRGF treatment and producing in vivo the greatest decrease in wound size under s-PRGF treatment. These findings highlight that the manufacturing process of the blood derivatives may modulate the efficacy of the final product.

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.

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

Activation of checkpoint kinase 2 is critical for herpes simplex virus type 1 replication in corneal epithelium.

PubMed

Alekseev, Oleg; Limonnik, Vladimir; Donovan, Kelly; Azizkhan-Clifford, Jane

2015-01-01

Herpes simplex virus (HSV) type I keratitis remains a leading cause of corneal morbidity, despite the availability of effective antiviral drugs. Improved understanding of virus-host interactions at the level of the host DNA damage response (DDR), a known factor in the development of HSV-1 keratitis, may shed light on potential new therapeutic targets. This report examines the role of checkpoint kinase 2 (Chk2), a DDR mediator protein, in corneal epithelial HSV-1 infection. A small-molecule inhibitor of Chk2 (Chk2 inhibitor II) was applied to HSV-1-infected cultured human corneal epithelial cells (hTCEpi and HCE) as well as to explanted and organotypically cultured human and rabbit corneas. Infection levels were assessed by plaque assay and real-time PCR. RNAi-mediated depletion of Chk2 was performed to confirm the effect of the inhibitor. Inhibition of the Chk2 kinase activity greatly suppresses the cytopathic effect, genome replication and infectious progeny production in vitro and ex vivo. This report demonstrates the critical role of Chk2 kinase in the establishment of HSV-1 corneal epithelial infection. These data contribute to our understanding of herpesvirus-host interactions and underscore the significance of DDR activation in HSV-1 keratitis.

Corneal Expression of SLURP-1 by Age, Sex, Genetic Strain, and Ocular Surface Health

PubMed Central

Swamynathan, Sudha; Delp, Emili E.; Harvey, Stephen A. K.; Loughner, Chelsea L.; Raju, Leela; Swamynathan, Shivalingappa K.

2015-01-01

Purpose Although secreted Ly6/urokinase-type plasminogen activator receptor–related protein-1 (Slurp1) transcript is highly abundant in the mouse cornea, corresponding protein expression remains uncharacterized. Also, SLURP1 was undetected in previous tear proteomics studies, resulting in ambiguity about its baseline levels. Here, we examine mouse corneal Slurp1 expression in different sexes, age groups, strains, and health conditions, and quantify SLURP1 in human tears from healthy or inflamed ocular surfaces. Methods Expression of Slurp1 in embryonic day-13 (E13), E16, postnatal day-1 (PN1), PN10, PN20, and PN70 Balb/C, FVBN, C57Bl/6, and DBA/2J mouse corneas, Klf4Δ/ΔCE corneas with corneal epithelial–specific ablation of Klf4, migrating cells in wild-type corneal epithelial wound edge, and in corneas exposed to pathogen-associated molecular patterns (PAMPs) poly(I:C), zymosan-A, or Pam3Csk4 was examined by QPCR, immunoblots, and immunofluorescent staining. Human SLURP1 levels were quantified by ELISA in tears from 34 men and women aged 18 to 80 years. Results Expression of Slurp1, comparable in different strains and sexes, was low in E13, E16, PN1, and PN10 mouse corneas, and increased rapidly after eyelid opening in a Klf4-dependent manner. We found Slurp1 was downregulated in corneas exposed to PAMPs, and in migrating cells at the wound edge. Human SLURP1 expression, comparable in different sexes and age groups, was significantly decreased in tears from inflamed ocular surfaces (0.34%) than those from healthy individuals (0.77%). Conclusions These data describe the influence of age, sex, genetic background, and ocular surface health on mouse corneal expression of Slurp1, establish the baseline for human tear SLURP1 expression, and identify SLURP1 as a useful diagnostic and/or therapeutic target for inflammatory ocular surface disorders. PMID:26670825

Corneal transplant

MedlinePlus

... and prevent eye movement during the surgery. The tissue for your corneal transplant will come from a person (donor) who has recently died. The donated cornea is processed and tested by a local eye bank to make sure it is safe for use ...

Corneal epithelium and UV-protection of the eye.

PubMed

Ringvold, A

1998-04-01

To study UV-absorption and UV-induced fluorescence in the bovine corneal epithelium. Spectrophotometry and spectrofluorimetry. The corneal epithelium absorbs UV-B radiation mainly owing to its content of protein, RNA, and ascorbate. Some of the absorbed energy is transformed to the less biotoxic UV-A radiation by fluorescence. RNA and ascorbate reduce tissue fluorescence. The corneal epithelium acts as a UV-filter, protecting internal eye structures through three different mechanisms: (1) Absorption of UV-B roughly below 310 nm wavelength. (2) Fluorescence-mediated ray transformation to longer wavelengths. (3) Fluorescence reduction. The extremely high ascorbate concentration in the corneal epithelium has a key role in two of these processes.

The cytotoxic effect of oxybuprocaine on human corneal epithelial cells by inducing cell cycle arrest and mitochondria-dependent apoptosis.

PubMed

Fan, W-Y; Wang, D-P; Wen, Q; Fan, T-J

2017-08-01

Oxybuprocaine (OBPC) is a widely used topical anesthetic in eye clinic, and prolonged and repeated usage of OBPC might be cytotoxic to the cornea, especially to the outmost corneal epithelium. In this study, we characterized the cytotoxic effect of OBPC on human corneal epithelial (HCEP) cells and investigated its possible cellular and molecular mechanisms using an in vitro model of non-transfected HCEP cells. Our results showed that OBPC at concentrations ranging from 0.025% to 0.4% had a dose- and time-dependent cytotoxicity to HCEP cells. Moreover, OBPC arrested the cells at S phase and induced apoptosis of these cells by inducing plasma membrane permeability, phosphatidylserine externalization, DNA fragmentation, and apoptotic body formation. Furthermore, OBPC could trigger the activation of caspase-2, -3, and -9, downregulate the expression of Bcl-xL, upregulate the expression of Bax along with the cytoplasmic amount of mitochondria-released apoptosis-inducing factor, and disrupt mitochondrial transmembrane potential. Our results suggest that OBPC has a dose- and time-dependent cytotoxicity to HCEP cells by inducing cell cycle arrest and cell apoptosis via a death receptor-mediated mitochondria-dependent proapoptotic pathway, and this novel finding provides new insights into the acute cytotoxicity and its toxic mechanisms of OBPC on HCEP cells.

Sensing inhomogeneous mechanical properties of human corneal Descemet's membrane with AFM nano-indentation.

PubMed

Di Mundo, Rosa; Recchia, Giuseppina; Parekh, Mohit; Ruzza, Alessandro; Ferrari, Stefano; Carbone, Giuseppe

2017-10-01

The paper describes a highly space-resolved characterization of the surface mechanical properties of the posterior human corneal layer (Descemet's membrane). This has been accomplished with Atomic Force Microscopy (AFM) nano-indentation by using a probe with a sharp tip geometry. Results indicate that the contact with this biological tissue in liquid occurs with no (or very low) adhesion. More importantly, under the same operating conditions, a broad distribution of penetration depth can be measured on different x-y positions of the tissue surface, indicating a high inhomogeneity of surface stiffness, not yet clearly reported in the literature. An important contribution to such inhomogeneity should be ascribed to the discontinuous nature of the collagen/proteoglycans fibers matrix tissue, as can be imaged by AFM when the tissue is semi-dry. Using classical contact mechanics calculations adapted to the specific geometry of the tetrahedral tip it has been found that the elastic modulus E of the material in the very proximity of the surface ranges from 0.23 to 2.6 kPa. Copyright © 2017 Elsevier Ltd. All rights reserved.

Causes of corneal graft failure in India.

PubMed

Dandona, L; Naduvilath, T J; Janarthanan, M; Rao, G N

1998-09-01

The success of corneal grafting in visual rehabilitation of the corneal blind in India depends on survival of the grafts. Understanding the causes of graft failure may help reduce the risk of failure. We studied these causes in a series of 638 graft failures at our institution. Multivariate logistic regression analysis was used to evaluate the association of particular causes of graft failure with indications for grafting, socioeconomic status, age, sex, host corneal vascularization, donor corneal quality, and experience of surgeon. The major causes of graft failure were allograft rejection (29.2%), increased intraocular pressure (16.9%), infection excluding endophthalmitis (15.4%), and surface problems (12.7%). The odds of infection causing graft failure were significantly higher in patients of lower socioeconomic status (odds ratio 2.45, 95% CI 1.45-4.15). Surface problems as a cause of graft failure was significantly associated with grafts done for corneal scarring or for regrafts (odds ratio 3.36, 95% CI 1.80-6.30). Increased intraocular pressure as a cause of graft failure had significant association with grafts done for aphakic or pseudophakic bullous keratopathy, congenital conditions or glaucoma, or regrafts (odds ratio 2.19, 95% CI 1.25-3.84). Corneal dystrophy was the indication for grafting in 12 of the 13 cases of graft failure due to recurrence of host disease. Surface problems, increased intraocular pressure, and infection are modifiable risk factors that are more likely to cause graft failure in certain categories of patients in India. Knowledge about these associations can be helpful in looking for and aggressively treating these modifiable risk factors in the at-risk categories of corneal graft patients. This can possibly reduce the chance of graft failure.

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.

Downstream effects of ROCK signaling in cultured human corneal stromal cells: microarray analysis of gene expression.

PubMed

Harvey, Stephen A K; Anderson, Susan C; SundarRaj, Nirmala

2004-07-01

Rho-associated coiled-coil-containing protein kinase (ROCK) is a downstream target of Rho GTPase signaling and regulates the assembly of stress fibers. Previous reports indicate that Rho/ROCK signaling is involved in the regulation of several cellular processes, some of which may be cell-type specific and are probably critical to corneal stromal cell activation. The present study identified ROCK-regulated gene expression in corneal stromal cells. Corneal stromal cells derived from eyes of three different donors were cultured to yield the following designated phenotypes: baseline fibroblasts (DMEM with 10% serum), activated fibroblasts (10% serum+bFGF+heparin), and myofibroblasts (1% serum+TGF-beta 1). Cells were exposed to the ROCK inhibitor Y-27632 or vehicle for 12 hours, and transcript levels altered by ROCK inhibition were identified with oligonucleotide microarrays (GeneChips; Affymetrix, Santa Clara, CA). In these phenotypes, Y-27632 caused marked (twofold or more) increases or decreases in 14/4, 12/3, and 15/10 transcripts. In both fibroblast groups Y-27632-treatment increased expression of endothelin receptors and of parathyroid hormone-like hormone. The upregulation of alpha-smooth muscle actin in myofibroblasts was attenuated by Y-27632. Combining data from all groups identified ROCK-supported (Y-27632 inhibitable) expression of 10 transcripts, including ribonucleotide reductase M2, the cyclin B1-CDC2-CKS2 system, and four mitotic spindle-associated proteins. ROCK inhibition causes broad inhibition of DNA synthesis and mitosis and causes changes that are different between (bFGF-activated) fibroblasts and (TGF-beta 1-induced) myofibroblasts. Thus, Rho/ROCK signaling regulates both common and distinct downstream events in corneal stromal cells activated (differentiated) to fibroblast or myofibroblast phenotype.

Corneal transplantation: A new view of life

PubMed Central

Amiri, Fardin; Ghiyasvandian, Shahrzad; Navab, Elham; Zakerimoghadam, Masoumeh

2017-01-01

Background The consequences of a corneal transplant are evaluated and classified by care providers, but understanding and interpretation of the results varies between patients, and creates different views for them and influences their lives in different ways while these influences are largely unknown. Aim This study aimed to explore understanding of new life in patients after corneal transplantation. Methods This qualitative study was conducted using a hermeneutic phenomenological approach in Tehran in 2016. Twelve corneal transplant recipients (7 men, 5 women) who were chosen purposefully from penetrating corneal transplant recipients, participated in this study. Semi-structured interviews were used to collect data. The content of the interviews was transcribed and analyzed using Van Manen’s methodology. Results Data analysis led to the emergence of several main themes, among which “having a new sense” and “fear and hope” were two of the most important themes. Conclusion It can be inferred from the overall participants’ experiences that corneal transplant has brought about a new look at life for patients. However, transplant-related issues are endless and continuous, and a sense of fear and hope has always surrounded them. PMID:28607635

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

Corneal pain without stain: is it real?

PubMed

Rosenthal, Perry; Baran, Inna; Jacobs, Deborah S

2009-01-01

Clinicians often encounter patients who report corneal pain suggestive of dry eye disease, yet lack equivalent signs. These patients represent a diagnostic and therapeutic challenge that is more easily dismissed than addressed. We review the physiology of pain and the pathophysiological mechanisms of neuropathic corneal pain and speculate on the mechanisms of certain etiopathogenic triggers, such as LASIK, severe dry eye disease, and Sjogren syndrome. Recognizing corneal neuropathic pain as a disease in its own right is the first step toward developing more effective treatments for these severely disabled and presently inadequately served patients.

Electrolytic removal of recurrence of granular corneal dystrophy.

PubMed

Mashima, Y; Kawashima, M; Yamada, M

2003-11-01

To report the efficacy of corneal electrolysis for the treatment of recurrent corneal opacities at the subepithelial region or at the host-graft interface of the stroma in granular corneal dystrophy (GCD). In patients with recurrences of opacities at the host-graft interface of the stroma after lamellar keratoplasty, the deep aspect of the graft was partially separated from host tissue to expose the deposits. The graft was everted, and electrolysis was applied directly to remove the deposits attached to both surfaces of the host and the graft. Then the graft was returned to its place and sutured. In patients with diffuse subepithelial opacities following penetrating keratoplasty, electrolysis was applied directly to the corneal surface. Deposits in the subepithelial region or at the host-graft interface of the stroma disappeared following treatment, and vision recovered. However, GCD recurred 2-3 years after the treatment. Corneal electrolysis is a simple, easy, and inexpensive way to remove deposits that recur after lamellar or penetrating keratoplasty for GCD.

Hypoxia attenuates inflammatory mediators production induced by Acanthamoeba via Toll-like receptor 4 signaling in human corneal epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pan, Hong; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, 107, Wenhua Xi Road, Jinan 250012; Wu, Xinyi, E-mail: xywu8868@163.com

2012-04-13

Highlights: Black-Right-Pointing-Pointer Hypoxia attenuates Acanthamoeba-induced the production of IL-8 and IFN-{beta}. Black-Right-Pointing-Pointer Hypoxia inhibits TLR4 expression in a time-dependent manner in HCECs. Black-Right-Pointing-Pointer Hypoxia inhibits Acanthamoeba-induced the activation of NF-{kappa}B and ERK1/2 in HCECs. Black-Right-Pointing-Pointer Hypoxia decreases Acanthamoeba-induced inflammatory response via TLR4 signaling. Black-Right-Pointing-Pointer LPS-induced the secretion of IL-6 and IL-8 is abated by hypoxia via TLR4 signaling. -- Abstract: Acanthamoeba keratitis (AK) is a vision-threatening corneal infection that is intimately associated with contact lens use which leads to hypoxic conditions on the corneal surface. However, the effect of hypoxia on the Acanthamoeba-induced host inflammatory response of corneal epithelial cellsmore » has not been studied. In the present study, we investigated the effect of hypoxia on the Acanthamoeba-induced production of inflammatory mediators interleukin-8 (IL-8) and interferon-{beta} (IFN-{beta}) in human corneal epithelial cells and then evaluated its effects on the Toll-like receptor 4 (TLR4) signaling, including TLR4 and myeloid differentiation primary response gene (88) (MyD88) expression as well as the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-{kappa}B) and extracellular signal-regulated kinases 1/2 (ERK1/2). We then studied the effect of hypoxia on a TLR4-specific inflammatory response triggered by the TLR4 ligand lipopolysaccharide (LPS). Our data showed that hypoxia significantly decreased the production of IL-8 and IFN-{beta}. Furthermore, hypoxia attenuated Acanthamoeba-triggered TLR4 expression as well as the activation of NF-{kappa}B and ERK1/2, indicating that hypoxia abated Acanthamoeba-induced inflammatory responses by affecting TLR4 signaling. Hypoxia also inhibited LPS-induced IL-6 and IL-8 secretion, myeloid differentiation primary response

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

Development of a program for toric intraocular lens calculation considering posterior corneal astigmatism, incision-induced posterior corneal astigmatism, and effective lens position.

PubMed

Eom, Youngsub; Ryu, Dongok; Kim, Dae Wook; Yang, Seul Ki; Song, Jong Suk; Kim, Sug-Whan; Kim, Hyo Myung

2016-10-01

To evaluate the toric intraocular lens (IOL) calculation considering posterior corneal astigmatism, incision-induced posterior corneal astigmatism, and effective lens position (ELP). Two thousand samples of corneal parameters with keratometric astigmatism ≥ 1.0 D were obtained using bootstrap methods. The probability distributions for incision-induced keratometric and posterior corneal astigmatisms, as well as ELP were estimated from the literature review. The predicted residual astigmatism error using method D with an IOL add power calculator (IAPC) was compared with those derived using methods A, B, and C through Monte-Carlo simulation. Method A considered the keratometric astigmatism and incision-induced keratometric astigmatism, method B considered posterior corneal astigmatism in addition to the A method, method C considered incision-induced posterior corneal astigmatism in addition to the B method, and method D considered ELP in addition to the C method. To verify the IAPC used in this study, the predicted toric IOL cylinder power and its axis using the IAPC were compared with ray-tracing simulation results. The median magnitude of the predicted residual astigmatism error using method D (0.25 diopters [D]) was smaller than that derived using methods A (0.42 D), B (0.38 D), and C (0.28 D) respectively. Linear regression analysis indicated that the predicted toric IOL cylinder power and its axis had excellent goodness-of-fit between the IAPC and ray-tracing simulation. The IAPC is a simple but accurate method for predicting the toric IOL cylinder power and its axis considering posterior corneal astigmatism, incision-induced posterior corneal astigmatism, and ELP.

Aniridia-related keratopathy: Structural changes in naïve and transplanted corneal buttons

PubMed Central

Stenevi, Ulf; Pedrosa Domellöf, Fátima

2018-01-01

Background To study structural changes in naïve and surgically treated corneas of aniridia patients with advanced aniridia-related keratopathy (ARK). Methods and findings Two naïve corneal buttons from patients with advanced ARK submitted to penetrating keratoplasty for the first time, one corneal button from an ARK patient that had undergone a keratolimbal allograft (KLAL), two corneal buttons from ARK patients who had previously undergone centered or decentered transplantation and were now retransplanted and two adult healthy donor control corneas were processed for immunohistochemistry. Antibodies against extracellular matrix components in the stroma and in the epithelial basement membrane (collagen I and IV, collagen receptor α11 integrin and laminin α3 chain), markers of fibrosis, wound healing and vascularization (fibronectin, tenascin-C, vimentin, α-SMA and caveolin-1), cell division (Ki-67) and macrophages (CD68) were used. Naïve ARK, KLAL ARK corneas and transplanted corneal buttons presented similar histopathological changes with irregular epithelium and disruption or absence of epithelial basal membrane. There was a loss of the orderly pattern of collagen lamellae and absence of collagen I in all ARK corneas. Vascularization was revealed by the presence of caveolin-1 and collagen IV in the pannus of all ARK aniridia corneas. The changes observed in decentered and centered transplants were analogous. Conclusions Given the similar pathological features of all cases, conditions inherent to the host seem to play an important role on the pathophysiology of the ARK in the long run. PMID:29889891

Effects of genipin corneal crosslinking in rabbit corneas.

PubMed

Avila, Marcel Y; Narvaez, Mauricio; Castañeda, Juan P

2016-07-01

To evaluate the effect of genipin, a natural crosslinking agent, in rabbit eyes. Department of Ophthalmology, Universidad Nacional de Colombia Centro de Tecnologia Oftalmica, Bogotá, Colombia. Experimental study. Ex vivo rabbit eyes (16; 8 rabbits) were treated with genipin 1.00%, 0.50%, and 0.25% for 5 minutes with a vacuum device to increase corneal permeability. Penetration was evaluated using Scheimpflug pachymetry (Pentacam). In the in vivo model (20 rabbits; 1 eye treated, 1 eye with vehicle), corneas were crosslinked with genipin as described. Corneal curvature, corneal pachymetry, and intraocular pressure (IOP) assessments as well as slitlamp examinations were performed 0, 7, 30, and 60 days after treatment. In the ex vivo model, Scheimpflug pachymetry showed deep penetration in the rabbit corneas with an increase in corneal density and a dose-dependent relationship. Corneal flattening was observed in treated eyes (mean 4.4 diopters ± 0.5 [SD]) compared with the control eyes. Pachymetry and IOP were stable in all evaluations. No eye showed toxicity in the anterior chamber or in the lens. Corneal crosslinking induced by genipin produced significant flattening of the cornea with no toxicity in rabbit eyes. This crosslinking could be useful in the treatment of corneal ectasia and in the modification of corneal curvature. None of the authors has a financial or proprietary interest in any material or method mentioned. Copyright © 2016 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Protease-activated receptor 2 (PAR2) is upregulated by Acanthamoeba plasminogen activator (aPA) and induces proinflammatory cytokine in human corneal epithelial cells.

PubMed

Tripathi, Trivendra; Abdi, Mahshid; Alizadeh, Hassan

2014-05-29

Acanthamoeba plasminogen activator (aPA) is a serine protease elaborated by Acanthamoeba trophozoites that facilitates the invasion of trophozoites to the host and contributes to the pathogenesis of Acanthamoeba keratitis (AK). The aim of this study was to explore if aPA stimulates proinflammatory cytokine in human corneal epithelial (HCE) cells via the protease-activated receptors (PARs) pathway. Acanthamoeba castellanii trophozoites were grown in peptone-yeast extract glucose for 7 days, and the supernatants were collected and centrifuged. The aPA was purified using the fast protein liquid chromatography system, and aPA activity was determined by zymography assays. Human corneal epithelial cells were incubated with or without aPA (100 μg/mL), PAR1 agonists (thrombin, 10 μM; TRAP-6, 10 μM), and PAR2 agonists (SLIGRL-NH2, 100 μM; AC 55541, 10 μM) for 24 and 48 hours. Inhibition of PAR1 and PAR2 involved preincubating the HCE cells for 1 hour with the antagonist of PAR1 (SCH 79797, 60 μM) and PAR2 (FSLLRY-NH2, 100 μM) with or without aPA. Human corneal epithelial cells also were preincubated with PAR1 and PAR2 antagonists and then incubated with or without PAR1 agonists (thrombin and TRAP-6) and PAR2 agonists (SLIGRL-NH2 and AC 55541). Expression of PAR1 and PAR2 was examined by quantitative RT-PCR (qRT-PCR), flow cytometry, and immunocytochemistry. Interleukin-8 expression was quantified by qRT-PCR and ELISA. Human corneal epithelial cells constitutively expressed PAR1 and PAR2 mRNA. Acanthamoeba plasminogen activator and PAR2 agonists significantly upregulated PAR2 mRNA expression (1- and 2-fold, respectively) (P < 0.05). Protease-activated receptor 2 antagonist significantly inhibited aPA, and PAR2 agonists induced PAR2 mRNA expression in HCE cells (P < 0.05). Protease-activated receptor 1 agonists, but not aPA, significantly upregulated PAR1 mRNA expression, which was significantly inhibited by PAR1 antagonist in HCE cells. Acanthamoeba plasminogen

Airbag induced corneal ectasia.

PubMed

Mearza, Ali A; Koufaki, Fedra N; Aslanides, Ioannis M

2008-02-01

To report a case of airbag induced corneal ectasia. Case report. A patient 3 years post-LASIK developed bilateral corneal ectasia worse in the right eye following airbag deployment in a road traffic accident. At last follow up, best corrected vision was 20/40 with -4.00/-4.00 x 25 in the right eye and 20/25 with -1.25/-0.50 x 135 in the left eye. This is a rare presentation of trauma induced ectasia in a patient post-LASIK. It is possible that reduction in biomechanical integrity of the cornea from prior refractive surgery contributed to this presentation.

Modern Corneal Eye-Banking Using a Software-Based IT Management Solution.

PubMed

Kern, C; Kortuem, K; Wertheimer, C; Nilmayer, O; Dirisamer, M; Priglinger, S; Mayer, W J

2018-01-01

Increasing government legislation and regulations in manufacturing have led to additional documentation regarding the pharmaceutical product requirements of corneal grafts in the European Union. The aim of this project was to develop a software within a hospital information system (HIS) to support the documentation process, to improve the management of the patient waiting list and to increase informational flow between the clinic and eye bank. After an analysis of the current documentation process, a new workflow and software were implemented in our electronic health record (EHR) system. The software takes over most of the documentation and reduces the time required for record keeping. It guarantees real-time tracing of all steps during human corneal tissue processing from the start of production until allocation during surgery and includes follow-up within the HIS. Moreover, listing of the patient for surgery as well as waiting list management takes place in the same system. The new software for corneal eye banking supports the whole process chain by taking over both most of the required documentation and the management of the transplant waiting list. It may provide a standardized IT-based solution for German eye banks working within the same HIS.

Changes in corneal endothelial cell density and the cumulative risk of corneal decompensation after Ahmed glaucoma valve implantation.

PubMed

Kim, Kyoung Nam; Lee, Sung Bok; Lee, Yeon Hee; Lee, Jong Joo; Lim, Hyung Bin; Kim, Chang-Sik

2016-07-01

To evaluate changes in the corneal endothelial cell density (ECD) and corneal decompensation following Ahmed glaucoma valve (AGV) implantation. This study was retrospective and observational case series. Patients with refractory glaucoma who underwent AGV implantation and were followed >5 years were consecutively enrolled. We reviewed the medical records, including the results of central corneal specular microscopy. Of the 127 enrolled patients, the annual change in ECD (%) was determined using linear regression for 72 eyes evaluated at least four times using serial specular microscopic examination and compared with 31 control eyes (fellow glaucomatous eyes under medical treatment). The main outcome measures were cumulative risk of corneal decompensation and differences in the ECD loss rates between subjects and controls. The mean follow-up after AGV implantation was 43.1 months. There were no cases of postoperative tube-corneal touch. The cumulative risk of corneal decompensation was 3.3%, 5 years after AGV implantation. There was a more rapid loss of ECD in the 72 subject eyes compared with the 31 controls (-7.0% and -0.1%/year, respectively; p<0.001). However, the rate of loss decreased over time and statistical significance compared with control eyes disappeared after 2 years postoperatively: -10.7% from baseline to 1 year (p<0.01), -7.0% from 1 year to 2 years (p=0.037), -4.2% from 2 years to 3 years (p=0.230) and -2.7% from 3 years to the final follow-up (p=0.111). In case of uncomplicated AGV implantation, the cumulative risk of corneal decompensation was 3.3%, 5 years after the operation. The ECD loss was statistically greater in eyes with AGV than in control eyes without AGV, but the difference was significant only up to 2 years post surgery. 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/.

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.

Surgically induced astigmatism after phacoemulsification by temporal clear corneal and superior clear corneal approach: a comparison.

PubMed

Nikose, Archana Sunil; Saha, Dhrubojyoti; Laddha, Pradnya Mukesh; Patil, Mayuri

2018-01-01

Cataract surgery has undergone various advances since it was evolved from ancient couching to the modern phacoemulsification cataract surgery. Surgically induced astigmatism (SIA) remains one of the most common complications. The introduction of sutureless clear corneal incision has gained increasing popularity worldwide because it offers several advantages over the traditional sutured limbal incision and scleral tunnel. A clear corneal incision has the benefit of being bloodless and having an easy approach, but SIA is still a concern. In this study, we evaluated the SIA in clear corneal incisions with temporal approach and superior approach phacoemulsification. Comparisons between the two incisions were done using keratometric readings of preoperative and postoperative refractive status. It was a hospital-based prospective interventional comparative randomized control trial of 261 patients conducted in a rural-based tertiary care center from September 2012 to August 2014. The visual acuity and detailed anterior segment and posterior segment examinations were done and the cataract was graded according to Lens Opacification Classification System II. Patients were divided for phacoemulsification into two groups, group A and group B, who underwent temporal and superior clear corneal approach, respectively. The patients were followed up on day 1, 7, 30, and 90 postoperatively. The parameters recorded were uncorrected visual acuity, best-corrected visual acuity, slit lamp examination, and keratometry. The mean difference of SIA between 30th and 90th day was statistically evaluated using paired t -test, and all the analyses were performed using SPSS 18.0 (SPSS Inc.) software. The mean postoperative SIA in group A was 0.998 D on the 30th day, which reduced to 0.768 D after 90 days, and in group B the SIA after 30 days was 1.651 D, whereas it reduced to 1.293 D after 90 days. Temporal clear corneal incision is evidently better than superior clear corneal incision as far as

Quantitative analysis of corneal stromal riboflavin concentration without epithelial removal.

PubMed

Rubinfeld, Roy S; Stulting, R Doyle; Gum, Glenwood G; Talamo, Jonathan H

2018-02-01

To compare the corneal stromal riboflavin concentration and distribution using 2 transepithelial corneal crosslinking (CXL) systems. Absorption Systems, San Diego, California, USA. Experimental study. The stromal riboflavin concentration of 2 transepithelial CXL systems was compared in rabbit eyes in vivo. The systems were the Paracel/Vibex Xtra, comprising riboflavin 0.25% solution containing TRIS and ethylenediaminetetraacetic acid and an isotonic solution of riboflavin 0.25%, (Group 1) and the CXLO system (Group 2). Manufacturers' Instructions For Use were followed. The intensity of riboflavin fluorescence by slitlamp observation 10, 15, and 20 minutes after instillation was graded on a scale of 0 to 5. The animals were humanely killed and the corneal stromal samples analyzed with liquid chromatography and mass spectrometry. The mean riboflavin fluorescence intensity grades in Group 1 (4 eyes) were 3.8, 4.8, and 4.8 at 10, 15, and 20 minutes, respectively. The mean grades in Group 2 (3 eyes) were 2.0, 2.3, and 2.0, respectively. The riboflavin distribution was uniform in Group 1 but not in Group 2. The mean riboflavin concentration by liquid chromatography and mass spectrometry was 27.0 μg/g stromal tissue in Group 1 and 6.7 μg/g in Group 2. A stromal riboflavin concentration theoretically adequate for CXL, 15 μg/g, was achieved in all eyes in Group 1 and no eyes in Group 2. Slitlamp grading correlated well with liquid chromatography and mass spectrometry concentration (R 2  = 0.940). The system used in Group 1 produced corneal riboflavin concentrations that were theoretically adequate for effective transepithelial CXL (≥15 μg/g), while the system in Group 2 did not. Slitlamp grading successfully estimated the corneal riboflavin concentration and can be used to ensure an adequate concentration of riboflavin in the cornea for transepithelial CXL. Copyright © 2018 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Impact of Facial Conformation on Canine Health: Corneal Ulceration

PubMed Central

Packer, Rowena M. A.; Hendricks, Anke; Burn, Charlotte C.

2015-01-01

Concern has arisen in recent years that selection for extreme facial morphology in the domestic dog may be leading to an increased frequency of eye disorders. Corneal ulcers are a common and painful eye problem in domestic dogs that can lead to scarring and/or perforation of the cornea, potentially causing blindness. Exaggerated juvenile-like craniofacial conformations and wide eyes have been suspected as risk factors for corneal ulceration. This study aimed to quantify the relationship between corneal ulceration risk and conformational factors including relative eyelid aperture width, brachycephalic (short-muzzled) skull shape, the presence of a nasal fold (wrinkle), and exposed eye-white. A 14 month cross-sectional study of dogs entering a large UK based small animal referral hospital for both corneal ulcers and unrelated disorders was carried out. Dogs were classed as affected if they were diagnosed with a corneal ulcer using fluorescein dye while at the hospital (whether referred for this disorder or not), or if a previous diagnosis of corneal ulcer(s) was documented in the dogs’ histories. Of 700 dogs recruited, measured and clinically examined, 31 were affected by corneal ulcers. Most cases were male (71%), small breed dogs (mean± SE weight: 11.4±1.1 kg), with the most commonly diagnosed breed being the Pug. Dogs with nasal folds were nearly five times more likely to be affected by corneal ulcers than those without, and brachycephalic dogs (craniofacial ratio <0.5) were twenty times more likely to be affected than non-brachycephalic dogs. A 10% increase in relative eyelid aperture width more than tripled the ulcer risk. Exposed eye-white was associated with a nearly three times increased risk. The results demonstrate that artificially selecting for these facial characteristics greatly heightens the risk of corneal ulcers, and such selection should thus be discouraged to improve canine welfare. PMID:25969983

Moesin as a key cytoskeleton regulator in corneal fibrosis.

PubMed

Zhu, Hong-Yuan; Yeo, Sia-Wey; Ng, Jennifer; Htoon, Hla Myint; Beuerman, R W

2013-04-01

: Corneal fibrosis is the third leading cause of blindness worldwide. α-Smooth muscle actin (SMA), a marker of fibrosis, is closely regulated through an intermediate group of submembrane molecules - cytoskeleton regulators. The purpose of this study was to elucidate the role of specific cytoskeleton regulators in a mouse model of corneal fibrosis. : A mouse model of corneal fibrosis was developed using anterior keratectomy (AK) and the topical application of transforming growth factor (TGF)-β1 (1 μg/ml). The RT² Profiler™ PCR Array for cytoskeleton regulators was used to assay changes in levels of specific members of this class of proteins. Moesin siRNA was delivered into the corneal stroma by iontophoresis in vivo. Transformation of the corneal keratocyte-to-myofibroblast in corneal fibrosis, as defined by the expression of α-SMA, was determined by Western blot. : After AK and topical application of TGF-β1, moesin was the most highly upregulated gene among 84 cytoskeleton regulator genes; iontophoresing moesin siRNA into the corneal stroma reduced the expression of α-SMA to 0.22-, 0.52-, and 0.31-fold of control at postoperative (PO) day 1, 3, and 5, respectively; also, upregulation of phospho-Smad 2 induced by TGF-β1 was reduced by moesin siRNA to 0.59-, 0.56-, and 0.31-fold of control and expression of phospho-Smad 3 was reduced to 0.58-, 0.53-, and 0.47-fold of control at the same PO days. : Moesin may be a potential drug target for inhibiting corneal fibrosis, and the details of moesin-related signaling pathways would be critical for understanding corneal fibrosis. Copyright © 2013 Elsevier Inc. All rights reserved.

En face optical coherence tomography angiography for corneal neovascularisation.

PubMed

Ang, Marcus; Cai, Yijun; Shahipasand, Shahab; Sim, Dawn A; Keane, Pearse A; Sng, Chelvin C A; Egan, Catherine A; Tufail, Adnan; Wilkins, Mark R

2016-05-01

Recently, there has been an increasing clinical need for objective evaluation of corneal neovascularisation, a condition which cause significant ocular morbidity. We describe the use of a rapid, non-invasive 'en face' optical coherence tomography angiography (OCTA) system for the assessment of corneal neovascularisation. Consecutive patients with abnormal corneal neovascularisation were scanned using a commercially available AngioVue OCTA system (Optovue, Fremont, California, USA) with the split-spectrum amplitude decorrelation angiography algorithm, using an anterior segment lens adapter. Each subject had four scans in each eye by a trained operator and two independent masked assessors analysed all images. Main outcome measures were scan quality (signal strength, image quality), area of neovascularisation and repeatability of corneal vascular grade. We performed OCTA in 20 patients (11 men, 9 women, mean age 49.27±17.23 years) with abnormal corneal neovascularisation. The mean area of corneal neovascularisation was 0.57±0.30 mm(2) with a mean neovascularisation grade of 3.5±0.2 in the OCTA scans. We found the OCTA to produce good quality images of the corneal vessels (signal strength: 36.95±13.97; image quality score 2.72±1.07) with good repeatability for assessing neovascularisation grade (κ=0.84). In this preliminary clinical study, we describe a method for acquiring angiography images with 'en face' views, using an OCTA system adapted for the evaluation of corneal neovascularisation. Further studies are required to compare the scans to other invasive angiography techniques for the quantitative evaluation of abnormal corneal vessels. 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/

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.

High-intensity corneal collagen crosslinking with riboflavin and UVA in rat cornea.

PubMed

Zhu, Yirui; Reinach, Peter S; Zhu, Hanlei; Tan, Qiufan; Zheng, Qinxiang; Qu, Jia; Chen, Wei

2017-01-01

Corneal collagen cross-linking (CXL) halts human corneal ectasias progression by increasing stromal mechanical stiffness. Although some reports describe that this procedure is effective in dealing with some infectious and immunologic corneal thinning diseases, there is a need for more animal models whose corneal thickness more closely resemble those occurring in these patients. To meet this need, we describe here high-intensity protocols that are safe and effective for obtaining CXL in rat corneas. Initially, a range of potentially effective UVA doses were evaluated based on their effectiveness in increasing tissue enzymatic resistance to dissolution. At UVA doses higher than a threshold level of 0.54 J/cm2, resistance to enzymatic digestion increased relative to that in non-irradiated corneas. Based on the theoretical threshold CXL dose, a CXL regimen was established in which the UVA tissue irradiance was 9 mW/cm2, which was delivered at doses of either 2.16, 2.7 or 3.24 J/cm2. Their dose dependent effects were evaluated on ocular surface morphological integrity, keratocyte apoptotic frequency, tissue thickness and endothelial cell layer density. Doses of 2.16 and 2.7 J/cm2 transiently decreased normal corneal transparency and increased thickness. These effects were fully reversed after 14 days. In contrast, 3.24 J/cm2 had more irreversible side effects. Three days after treatment, apoptotic frequency in the CXL-2.16 group was lower than that at higher doses. Endothelial cell losses remained evident only in the CXL-3.24 group at 42 days posttreatment. Stromal fiber thickening was evident in all the CXL-treated groups. We determined both the threshold UVA dose using the high-intensity CXL procedure and identified an effective dose range that provides optimal CXL with minimal transient side effects in the rat cornea. These results may help to provide insight into how to improve the CXL outcome in patients afflicted with a severe corneal thinning disease.

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

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

Structure of corneal layers, collagen fibrils, and proteoglycans of tree shrew cornea.

PubMed

Almubrad, Turki; Akhtar, Saeed

2011-01-01

The stroma is the major part of the cornea, in which collagen fibrils and proteoglycans are distributed uniformly. We describe the ultrastructure of corneal layers, collagen fibrils (CF), and proteoglycans (PGs) in the tree shrew cornea. Tree shrew corneas (5, 6, and 10 week old animals) and normal human corneas (24, 25, and 54 years old) were fixed in 2.5% glutaraldehyde containing cuprolinic blue in a sodium acetate buffer. The tissue was processed for electron microscopy. The 'iTEM Olympus Soft Imaging Solutions GmbH' program was used to measure the corneal layers, collagen fibril diameters and proteoglycan areas. The tree shrew cornea consists of 5 layers: the epithelium, Bowman's layer, stroma, Descemet's membrane, and endothelium. The epithelium was composed of squamous cells, wing cells and basal cells. The Bowman's layer was 5.5±1.0 µm thick and very similar to a normal human Bowman's layer. The stroma was 258±7.00 µm thick and consisted of collagen fibril lamellae. The lamellae were interlaced with one another in the anterior stroma, but ran parallel to one another in the middle and posterior stroma. Collagen fibrils were decorated with proteoglycan filaments with an area size of 390 ±438 nm(2). The collagen fibril had a minimum diameter of 39±4.25 nm. The interfibrillar spacing was 52.91±6.07 nm. Within the collagen fibrils, very small electron-dense particles were present. The structure of the tree shrew cornea is very similar to that of the normal human cornea. As is the case with the human cornea, the tree shrew cornea had a Bowman's layer, lamellar interlacing in the anterior stroma and electron-dense particles within the collagen fibrils. The similarities of the tree shrew cornea with the human cornea suggest that it could be a good structural model to use when studying changes in collagen fibrils and proteoglycans in non-genetic corneal diseases, such as ectasia caused after LASIK (laser-assisted in situ keratomileusis).

Structure of corneal layers, collagen fibrils, and proteoglycans of tree shrew cornea

PubMed Central

Almubrad, Turki

2011-01-01

Purpose The stroma is the major part of the cornea, in which collagen fibrils and proteoglycans are distributed uniformly. We describe the ultrastructure of corneal layers, collagen fibrils (CF), and proteoglycans (PGs) in the tree shrew cornea. Methods Tree shrew corneas (5, 6, and 10 week old animals) and normal human corneas (24, 25, and 54 years old) were fixed in 2.5% glutaraldehyde containing cuprolinic blue in a sodium acetate buffer. The tissue was processed for electron microscopy. The ‘iTEM Olympus Soft Imaging Solutions GmbH’ program was used to measure the corneal layers, collagen fibril diameters and proteoglycan areas. Results The tree shrew cornea consists of 5 layers: the epithelium, Bowman’s layer, stroma, Descemet’s membrane, and endothelium. The epithelium was composed of squamous cells, wing cells and basal cells. The Bowman’s layer was 5.5±1.0 µm thick and very similar to a normal human Bowman’s layer. The stroma was 258±7.00 µm thick and consisted of collagen fibril lamellae. The lamellae were interlaced with one another in the anterior stroma, but ran parallel to one another in the middle and posterior stroma. Collagen fibrils were decorated with proteoglycan filaments with an area size of 390 ±438 nm2. The collagen fibril had a minimum diameter of 39±4.25 nm. The interfibrillar spacing was 52.91±6.07 nm. Within the collagen fibrils, very small electron-dense particles were present. Conclusions The structure of the tree shrew cornea is very similar to that of the normal human cornea. As is the case with the human cornea, the tree shrew cornea had a Bowman's layer, lamellar interlacing in the anterior stroma and electron-dense particles within the collagen fibrils. The similarities of the tree shrew cornea with the human cornea suggest that it could be a good structural model to use when studying changes in collagen fibrils and proteoglycans in non-genetic corneal diseases, such as ectasia caused after LASIK (laser

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.

Modeling Corneal Oxygen with Scleral Gas Permeable Lens Wear.

PubMed

Compañ, Vicente; Aguilella-Arzo, Marcel; Edrington, Timothy B; Weissman, Barry A

2016-11-01

The main goal of this current work is to use an updated calculation paradigm, and updated boundary conditions, to provide theoretical guidelines to assist the clinician whose goal is to improve his or her scleral gas permeable (GP) contact lens wearing patients' anterior corneal oxygen supply. Our model uses a variable value of corneal oxygen consumption developed through Monod equations that disallows negative oxygen tensions within the stroma to predict oxygen tension at the anterior corneal surface of scleral GP contact lens wearing eyes, and to describe oxygen tension and flux profiles, for various boundary conditions, through the lens, tears, and cornea. We use several updated tissue and boundary parameters in our model. Tear exchange with GP scleral lenses is considered nonexistent in this model. The majority of current scleral GP contact lenses should produce some levels of corneal hypoxia under open eye conditions. Only lenses producing the thinnest of tear vaults should result in anterior corneal surface oxygen tensions greater than a presumed critical oxygen tension of 100 mmHg. We also find that corneal oxygen tension and flux are each more sensitive to modification in tear vault than to changes in lens oxygen permeability, within the ranges of current clinical manipulation. Our study suggests that clinicians would be prudent to prescribe scleral GP lenses manufactured from higher oxygen permeability materials and especially to fit without excessive corneal clearance.

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.

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.

COMPARISON OF PROLIFERATIVE CAPACITY OF GENETICALLY-ENGINEERED PIG AND HUMAN CORNEAL ENDOTHELIAL CELLS

PubMed Central

Fujita, Minoru; Mehra, Ruhina; Lee, Seung Eun; Roh, Danny S.; Long, Cassandra; Funderburgh, James L.; Ayares, David L.; Cooper, David K. C.; Hara, Hidetaka

2013-01-01

Purpose The possibility of providing cultured corneal endothelial cells (CECs) for clinical transplantation has gained much attention. However, the worldwide need for human (h) donor corneas far exceeds supply. The pig (p) might provide an alternative source. The aim of this study was to compare the proliferative capacity of CECs from wild-type (WT) pigs, genetically-engineered (GE) pigs, and humans. Methods The following CECs were cultured – hCECs from donors (i) ≤36 years (young), (ii) ≥49 years (old), and WT pCECs from (iii) neonatal (<5 days), (iv) young (<2 months), and (v) old (>20 months) pigs, and CECs from young (vi) GE pigs (GTKO/CD46 and GTKO/CD46/CD55). Proliferative capacity of CECs was assessed by direct cell counting over 15 days of culture and by BrdU assay. Cell viability during culture was assessed by annexin V staining. The MTT assay assessed cell metabolic activity. Results There was significantly lower proliferative capacity of old CECs than of young CECs (p<0.01) in both pigs and humans. There was no significant difference in proliferative capacity/metabolic activity between young pCECs and young hCECs. However, there was a significantly higher percentage of cell death in hCECs compared to pCECs during culture (p<0.01). Young GE pCECs showed similar proliferative capacity/cell viability/metabolic activity to young WT pCECs. Conclusions Because of the greater availability of young pigs and the excellent proliferative capacity of cultured GE pCECs, GE pigs could provide a source of CECs for clinical transplantation. PMID:23258190

In-vitro corneal transparency measuring system

NASA Astrophysics Data System (ADS)

Ventura, Liliane; da Costa Vieira, Marcelo A.; Isaac, Flavio; Chiaradia, Caio; Faria de Sousa, Sidney J.

2001-06-01

A system for measuring the average corneal transparency of preserved corneas has been developed in order to provide a more accurate and standard report of the corneal tissue. The donated cornea transparency is one of the features to be analyzed previously to its indication for the transplant. The small portable system consists of two main parts: the optical and the electronic parts. The optical system consists of a white light, lenses and pin-holes that collimate white light beams that illuminates the cornea in its preservative medium. The light that passes through the cornea is detected by a resistive detector and the average corneal transparency is shown in a display. In order to obtain just the tissue transparency, the electronic circuit was built in a way that there is a baseline input of the preservative medium, previous to the measurement of the corneal transparency. Manipulating the system consists of three steps: (1) Adjusting the zero percentage in the absence of light (at this time the detectors in the dark); (2) Placing the preservative medium in the system and adjusting the 100% value (this is the baseline input); (3) Preserving the cornea and placing it in the system. The system provides the tissue transparency. The system is connected to an endothelium evaluation system for Slit Lamp, that we have developed, and statistics about the relationship of the corneal transparency and density of the endothelial cells will be provided in the next years. The system is being used in a public Eye Bank in Brasil.

[Regulatory analysis of hypoxia on innate immunity of human corneal epithelium].

PubMed

Pang, K P; Pan, H; Wu, X Y

2016-11-15

Objective: To investigate the role of hypoxia on the regulation of innate immunity of human corneal epithelium. Methods: Telomerase-immortalized human epithelial cells (THCEs) were incubated under normoxia (21% O 2 ) or hypoxic (1% O 2 ) conditions respectively. After 6, 12, 24, 48 h culture, the mRNA and protein levels of toll like receptor 4 (TLR4) were measured by real-time polymerase chain reaction (RT-PCR) and Western blot analysis. After 24 h culture, THCEs of each group were challenged respectively with TLR4 ligand lipopolysaccharide (LPS) (1 μg/ml) for 6 h. RT-PCR was used to assess the mRNA level of myeloid differentiation factor 88 (MyD88), interleukin(IL)6, IL-8 and tumor necrosis factor α (TNF-α). Western blot was used to examine the protein level of inhibitor of nuclear factor kappa-B α (IκBα) and phosphorylated IκBα (p-IκBα). Enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion of the inflammatory cytokines IL-6, IL-8 and TNF-α. Results: The results of RT-PCR and Western blot analysis showed that the expression of TLR4 downregulated 90% and 55% respectively after hypoxic exposure for 48 h. Hypoxia also inhibited LPS-induced secretion of IL-6, IL-8, TNF-α, expression of MyD88 and activation of NF-κB. The mRNA level of MyD88 was diminished 63%, and the protein expression of p-IκBα was also lowered. Meanwhile, the secretions of IL-6, IL-8 and TNF-α under hypoxia were reduced (31%, 55% and 50% respectively). Conclusion: Hypoxia attenuated immune and inflammatory response of the cornea epithelium by suppressing TLR4 signaling, and could enhance cell susceptibility to microorganism infection.

Altered corneal biomechanical properties in children with osteogenesis imperfecta.

PubMed

Lagrou, Lisa M; Gilbert, Jesse; Hannibal, Mark; Caird, Michelle S; Thomas, Inas; Moroi, Sayoko E; Bohnsack, Brenda L

2018-04-07

To evaluate biomechanical corneal properties in children with osteogenesis imperfecta (OI). A prospective, observational, case-control study was conducted on children 6-19 years of age diagnosed with OI. Patients with OI and healthy control subjects underwent complete ophthalmic examinations. Additional tests included Ocular Response Analyzer (ORA) and ultrasonic pachymetry. Primary outcomes were central corneal thickness (CCT), corneal hysteresis (CH), and corneal resistance factor (CRF). Intraocular pressure (IOP) was measured directly by either iCare or Goldmann applanation and indirectly by the ORA (Goldmann-correlated and corneal-compensated IOP). Statistically significant differences between OI and control groups were determined using independent samples t test. A total of 10 of 18 OI cases (mean age, 13 ± 4.37 years; 8 males) and 30 controls (mean age, 12.76 ± 2.62 years; 16 males) were able to complete the corneal biomechanics and pachymetry testing. Children with OI had decreased CH (8.5 ± 1.0 mm Hg vs 11.6 ± 1.2 mm Hg [P < 0.001]), CRF (9.0 ± 1.9 mm Hg vs 11.5 ± 1.5 [P < 0.001]) and CCT (449.8 ± 30.8 μm vs 568 ± 47.6 μm [P < 0.001]) compared to controls. The corneal-compensated IOP was significantly higher in OI cases (18.8 ± 3.1 mm Hg) than in controls (15.0 ± 1.6 mm Hg, P < 0.004), but there was no significant difference in Goldmann-correlated IOP (16.3 ± 4.2 mm Hg vs 15.8 ± 2.2 mm Hg). Collagen defects in OI alter corneal structure and biomechanics. Children with OI have decreased CH, CRF, and CCT, resulting in IOPs that are likely higher than measured by tonometry. These corneal alterations are present at a young age in OI. Affected individuals should be routinely screened for glaucoma and corneal pathologies. Copyright © 2018 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

Biometry Characteristics in Adults and Children With Marfan Syndrome: From the Marfan Eye Consortium of Chicago.

PubMed

Kinori, Michael; Wehrli, Sarah; Kassem, Iris S; Azar, Nathalie F; Maumenee, Irene H; Mets, Marilyn B

2017-05-01

To report on the biometric findings of adults and children with Marfan syndrome (MFS) recruited from 2 annual National Marfan Foundation conferences (2012 and 2015). Cross-sectional study. Subjects diagnosed with MFS by Ghent 2 nosology were included for analysis. Subjects were divided into "adults" (≥16 years of age) and "children" (5-15 years of age). Biometric data included values for refractive error, axial length (AL), corneal curvature, anterior chamber depth, lens thickness, and central corneal thickness. Of the 117 subjects evaluated, 74 (35 adults, 32 children, and 7 children <5 years of age) had a definite diagnosis of MFS and were included in the study. The AL was longer (25.25 ± 0.32 mm vs 24.24 ± 0.33 mm, P = .03) and the lens was thicker (3.94 ± 0.09 mm vs 3.62 ± 0.10 mm, P = .03) in adults. Both groups had flat corneas (average keratometry [K med ] of 41.59 ± 0.35 diopters [D] in adults vs 40.89 ± 0.36 D in children, P = .17). A negative correlation was found between AL and K med (-0.33, P < .001). The corneas of patients with MFS with ectopia lentis (EL) were significantly flatter and with higher degree of corneal astigmatism compared to patients without EL (K med of 40.68 ± 0.31 D vs 41.75 ± 0.28 D, P < .01 and corneal astigmatism of 1.68 ± 0.16 D vs 1.13 ± 0.14 D, P = .01). Children with established MFS have flat corneas at least to the same degree as adults. Corneas of patients with MFS with EL are flatter and have a higher degree of corneal astigmatism. We strongly suggest that corneal parameters should be measured if MFS is suspected, especially in children that may not yet have developed EL. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Regulation of Corneal Stroma Extracellular Matrix Assembly

PubMed Central

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

2014-01-01