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Sample records for rabbit corneal equivalent

  1. Equivalence of topical clobetasone and dexamethasone in experimental corneal allograft rejection.

    PubMed Central

    Wilhelmus, K R; Hunter, P A; Rice, N S

    1981-01-01

    We produced experimental immune reactions by exchanging peripheral corneal transplants between rabbits. Clobetasone butyrate 0.1% and dexamethasone phosphate 0.1% eye drops were equally effective in delaying corneal allograft rejection. Images PMID:7032579

  2. Experimental herpetic keratitis in rabbit corneal organ cultures.

    PubMed Central

    Percy, D. H.; Creighton, M. O.; Hatch, L. A.; De Clercq, E.

    1984-01-01

    An in-vitro method for maintaining rabbit corneal organ cultures for short periods of time is described. These cultures supported replication of strains of type 1 and 2 herpes simplex virus, and changes typical of herpetic infections of the cornea in vivo were observed by light microscopy, and by scanning and transmission electron microscopy. Infectious virus was readily recovered from inoculated corneal organ cultures. For practical, economic and humanitarian reasons, the full potential of this system warrants further investigation. Images Fig. 2 Fig. 3 Fig. 1 Fig. 4 Fig. 5 Fig. 6 PMID:6320856

  3. Corneal Stroma Regeneration with Acellular Corneal Stroma Sheets and Keratocytes in a Rabbit Model

    PubMed Central

    Ma, Xiao Yun; Zhang, Yun; Zhu, Dan; Lu, Yang; Zhou, Guangdong; Liu, Wei; Cao, Yilin; Zhang, Wen Jie

    2015-01-01

    Acellular corneal stroma matrix has been used for corneal stroma engineering. However, because of its compact tissue structure, regrowth of keratocytes into the scaffold is difficult. Previously, we developed a sandwich model for cartilage engineering using acellular cartilage sheets. In the present study, we tested this model for corneal stroma regeneration using acellular porcine corneal stroma (APCS) sheets and keratocytes. Porcine corneas were decellularized by NaCl treatment, and the APCS was cut into 20-μm-thick sheets. A rabbit corneal stroma defect model was created by lamellar keratoplasty and repaired by transplantation of five pieces of APCS sheets with keratocytes. Six months after transplantation, transparent corneas were present in the experimental group, which were confirmed by anterior segment optical coherence tomography examination and transmittance examination. The biomechanical properties in the experimental group were similar to those of normal cornea. Histological analyses showed an even distribution of keratocytes and well-oriented matrix in the stroma layer in the experimental group. Together, these results demonstrated that the sandwich model using acellular corneal stroma sheets and keratocytes could be potentially useful for corneal stroma regeneration. PMID:26167895

  4. Benzalkonium Chloride Suppresses Rabbit Corneal Endothelium Intercellular Gap Junction Communication

    PubMed Central

    Zhang, Zhenhao; Huang, Yue; Xie, Hui; Pan, Juxin; Liu, Fanfei; Li, Xuezhi; Chen, Wensheng; Hu, Jiaoyue; Liu, Zuguo

    2014-01-01

    Purpose Gap junction intercellular communication (GJIC) plays a critical role in the maintenance of corneal endothelium homeostasis. We determined if benzalkonium chloride (BAK) alters GJIC activity in the rabbit corneal endothelium since it is commonly used as a drug preservative in ocular eyedrop preparations even though it can have cytotoxic effects. Methods Thirty-six adult New Zealand albino rabbits were randomly divided into three groups. BAK at 0.01%, 0.05%, and 0.1% was applied twice daily to one eye of each of the rabbits in one of the three groups for seven days. The contralateral untreated eyes were used as controls. Corneal endothelial morphological features were observed by in vivo confocal microscopy (IVCM). Immunofluorescent staining resolved changes in gap junction integrity and localization. Western blot analysis and RT-PCR evaluated changes in levels of connexin43 (Cx43) and tight junction zonula occludens-1 (ZO-1) gene and protein expression, respectively. Cx43 and ZO-1 physical interaction was detected by immunoprecipitation (IP). Primary rabbit corneal endothelial cells were cultured in Dulbecco's Modified Eagle Medium (DMEM) containing BAK for 24 hours. The scrape-loading dye transfer technique (SLDT) was used to assess GJIC activity. Results Topical administration of BAK (0.05%, 0.1%) dose dependently disrupted corneal endothelial cell morphology, altered Cx43 and ZO-1 distribution and reduced Cx43 expression. BAK also markedly induced increases in Cx43 phosphorylation status concomitant with decreases in the Cx43-ZO-1 protein-protein interaction. These changes were associated with marked declines in GJIC activity. Conclusions The dose dependent declines in rabbit corneal endothelial GJIC activity induced by BAK are associated with less Cx43-ZO-1 interaction possibly arising from increases in Cx43 phosphorylation and declines in its protein expression. These novel changes provide additional evidence that BAK containing eyedrop preparations

  5. Effect of acacia honey on cultured rabbit corneal keratocytes

    PubMed Central

    2014-01-01

    Background Acacia honey is a natural product which has proven to have therapeutic effects on skin wound healing, but its potential healing effects in corneal wound healing have not been studied. This study aimed to explore the effects of Acacia honey (AH) on corneal keratocytes morphology, proliferative capacity, cell cycle, gene and protein analyses. Keratocytes from the corneal stroma of six New Zealand white rabbits were isolated and cultured until passage 1. The optimal dose of AH in the basal medium (FD) and medium containing serum (FDS) for keratocytes proliferation was identified using MTT assay. The morphological changes, gene and protein expressions of aldehyde dehydrogenase (ALDH), marker for quiescent keratocytes and vimentin, marker for fibroblasts were detected using q-RTPCR and immunocytochemistry respectively. Flowcytometry was performed to evaluate the cell cycle analysis of corneal keratocytes. Results Cultured keratocytes supplemented with AH showed no morphological changes compared to control. Keratocytes cultured in FD and FDS media supplemented with 0.025% AH showed optimal proliferative potential compared with FD and FDS media, respectively. Gene expressions of ADLH and vimentin were increased in keratocytes cultured with AH enriched media. All proteins were expressed in keratocytes cultured in all media in accordance to the gene expression findings. No chromosomal changes were detected in keratocytes in AH enriched media. Conclusion Corneal keratocytes cultured in media supplemented with 0.025% AH showed an increase in proliferative capacity while retaining their morphology, gene and protein expressions with normal cell cycle. The results of the present study show promising role of AH role in accelerating the initial stage of corneal wound healing. PMID:24885607

  6. In Vivo Confocal Microscopic Observation of Lamellar Corneal Transplantation in the Rabbit Using Xenogenic Acellular Corneal Scaffolds as a Substitute

    PubMed Central

    Feng, Yun; Wang, Wei

    2015-01-01

    Background: The limiting factor to corneal transplantation is the availability of donors. Research has suggested that xenogenic acellular corneal scaffolds (XACS) may be a possible alternative to transplantation. This study aimed to investigate the viability of performing lamellar corneal transplantation (LCT) in rabbits using canine XACS. Methods: Fresh dog corneas were decellularized by serial digestion, and LCT was performed on rabbit eyes using xenogeneic decellularized corneal matrix. Cellular and morphological changes were observed by slit-lamp, light, and scanning electron microscopy at 7, 30 and 90 days postoperatively. Immunocytochemical staining for specific markers such as keratin 3, vimentin and MUC5AC, was used to identify cells in the graft. Results: Decellularized xenogenic corneal matrix remained transparent for about 1-month after LCT. The recipient cells were able to survive and proliferate into the grafts. Three months after transplantation, grafts had merged with host tissue, and graft epithelialization and vascularization had occurred. Corneal nerve fibers were able to grow into the graft in rabbits transplanted with XACS. Conclusions: Xenogenic acellular corneal scaffolds can maintain the transparency of corneal grafts about 1-month and permit growth of cells and nerve fibers, and is, therefore, a potential substitute or carrier for a replacement cornea. PMID:25836615

  7. Acanthamoebae bind to glycolipids of rabbit corneal epithelium.

    PubMed Central

    Panjwani, N; Zhao, Z; Baum, J; Pereira, M; Zaidi, T

    1992-01-01

    By use of a thin-layer chromatogram (TLC) overlay procedure, 35S-labeled acanthamoebae were shown to bind to seven glycolipids of rabbit corneal epithelium. Corneal epithelial cells were grown in culture and were subjected to Folch extraction to isolate a chloroform-rich lower phase containing neutral glycosphingolipids (NGSL) and an aqueous upper phase containing gangliosides, i.e., sialic acid-containing glycolipids. Thin-layer chromatography of the upper phase revealed the presence of 10 ganglioside components. Acanthamoebae were shown to bind to four of these components, referred to as 2, 3, 6, and 7. On TLC plates, ganglioside components 2 and 3 migrated slightly ahead of the glycolipid standard GD1a, component 7 comigrated with standard GM3, and component 6 migrated a little more slowly than GM3. Likewise, of the 10 NGSL known to be present in the lower phase, acanthamoebae bound to components 1, 5, and 6. NGSL components 1, 5, and 6 migrated on TLC plates with relative mobilities similar to those of standards asialo GM1, asialo GM2, and ceramidetrihexoside, respectively. We propose that one or more of the Acanthamoeba-reactive glycolipids of corneal epithelium identified in this study may play a role in the pathogenesis of Acanthamoeba keratitis by mediating the adherence of the parasites to the cornea. Images PMID:1639517

  8. Inhibitory effect of polysulfated heparin endostatin on alkali burn induced corneal neovascularization in rabbits

    PubMed Central

    Li, Zhao-Na; Yuan, Zhong-Fang; Mu, Guo-Ying; Hu, Ming; Cao, Li-Jun; Zhang, Ya-Li; Liu, Lei; Ge, Ming-Xu

    2015-01-01

    AIM To investigate anti-angiogenic effects of polysulfated heparin endostatin (PSH-ES) on alkali burn induced corneal neovascularization (NV) in rabbits. METHODS An alkali burn was made on rabbit corneas to induce corneal NV in the right eye of 24 rabbits. One day after burn creation, a 0.2 mL subconjunctival injection of 50 µg/mL PSH-ES, 50 µg/mL recombinant endostatin (ES), or normal saline was administered every other day for a total of 14d (7 injections). Histology and immunohistochemisty were used to examine corneas. Corneal NV growth was evaluated as microvessel quantity and corneal vascular endothelial growth factor (VEGF) expression was measured by immunohistochemical assay. RESULTS Subconjunctival injection of ES and PSH-ES resulted in significant corneal NV suppression, but PSH-ES had a more powerful anti-angiogenic effect than ES. Mean VEGF concentration in PSH-ES treated corneas was significantly lower than in ES treated and saline treated corneas. Histological examination showed that corneas treated with either PSH-ES or ES had significantly fewer microvessels than eyes treated with saline. Additionally corneas treated with PSH-ES had significantly fewer microvessels than corneas treated with ES. CONCLUSION Both PSH-ES and recombinant ES effectively inhibit corneal NV induced by alkali burn. However, PSH-ES is a more powerful anti-angiogenic agent than ES. This research has the potential to provide a new treatment option for preventing and treating corneal NV. PMID:25938033

  9. The effects of sub-solar levels of UV-A and UV-B on rabbit corneal and lens epithelial cells.

    PubMed

    Rogers, Christian S; Chan, Lai-Man; Sims, Yolanda S; Byrd, Krashod D; Hinton, Danielle L; Twining, Sally S

    2004-05-01

    The purpose of this work was to establish whether exposing cultured rabbit corneal and lens epithelial cells to ultraviolet radiation equivalent to several hours under the sun would damage the cells. Confluent rabbit corneal epithelial cells were irradiated with broadband UV-A or UV-B, and confluent lens epithelial cells were irradiated with broadband UV-A. The maximum dose of UV-A was 6.3 J cm(-2) and that of UV-B was 0.60 J cm(-2). Damage to corneal epithelial cell was studied using the terminal deoxynucleotidyl transferase mediated dUTP-X nick end labeling (TUNEL) assay and damage to lens epithelial cell was studied using the single cell gel electrophoresis (comet) assay and trypan blue exclusion assay. Lipid peroxidation was assayed using the thiobarbituric acid reaction. Both UV-B and UV-A induced cell death in corneal epithelial cells with different latent periods. UV-A damage included cell death, decreased viability and increased lipid peroxidation of lens epithelial cell. In addition, UV irradiation of the corneal and lens epithelial cells decreased the activity of catalase to thirty to fifty percent of its original value, while the activities of glutathione peroxidase and superoxide dismutase did not decrease within experimental error. Thus, even sub-solar UV radiation can cause irreversible damage to corneal and lens epithelial cells. PMID:15051481

  10. Multipurpose Care Solution–Induced Corneal Surface Disruption and Pseudomonas aeruginosa Internalization in the Rabbit Corneal Epithelium

    PubMed Central

    Posch, Leila C.; Zhu, Meifang; Robertson, Danielle M.

    2014-01-01

    Purpose. To evaluate the effects of a chemically preserved multipurpose contact lens care solution (MPS) on the corneal epithelial surface and Pseudomonas aeruginosa (PA) internalization in the rabbit corneal epithelium. Methods. Rabbits were fit in one eye with a silicone hydrogel lens (balafilcon A) soaked overnight in a borate-buffered MPS (BioTrue). The contralateral eye was fit with a lens removed directly from the blister pack containing borate-buffered saline (control). Lenses were worn for 2 hours. Upon lens removal, corneas were challenged ex vivo with invasive PA strain 6487 and assessed for PA internalization. Ultrastructural changes were assessed using scanning electron (SEM) and transmission electron microscopy (TEM). Results. Scanning electron microscopy showed frank loss of surface epithelium in MPS-exposed eyes, while control eyes exhibited occasional loss of surface membranes but retention of intact junctional borders. Transmission electron microscopy data supported and extended SEM findings, demonstrating the presence of epithelial edema in MPS-treated eyes. There was a 12-fold increase in PA uptake into the corneal epithelium following wear of the MPS-treated lens compared to control (P = 0.008). Conclusions. These data demonstrate that corneal exposure to MPS during lens wear damages the surface epithelium and are consistent with our previous clinical data showing an increase in bacterial binding to exfoliated epithelial cells following MPS use with resultant increased risk for lens-mediated infection. These findings also demonstrate that the PA invasion assay may provide a highly sensitive quantitative metric for assessing the physiological impact of lens-solution biocompatibility on the corneal epithelium. PMID:24876286

  11. Lack of association between VAP-1/SSAO activity and corneal neovascularization in a rabbit model.

    PubMed

    Énzsöly, Anna; Markó, Katalin; Tábi, Tamás; Szökő, Éva; Zelkó, Romána; Tóth, Miklós; Petrash, J Mark; Mátyus, Péter; Németh, János

    2013-06-01

    The aim of this study is to determine the efficacy of a potent and specific vascular adhesive protein-1/semicarbazide-sensitive amine oxidase (VAP-1/SSAO) inhibitor, LJP 1207, as a potential antiangiogenic and anti-inflammatory agent in the therapy of corneal neovascularization. Corneal neovascularization was induced with intrastromal suturing in rabbits (n = 20). Topical treatment with VAP-1/SSAO inhibitor LJP 1207 (n = 5, 4 times a day), bevacizumab (n = 5, daily), their combination (n = 5) and vehicle only (n = 5, 4 times a day) were applied postoperatively for 2 weeks. The development and extent of corneal neovascularization were evaluated by digital image analysis. At the end of the observation period, the level of corneal and serum VAP-1/SSAO activity was measured fluorometrically and radiochemically. The corneal VAP-1/SSAO activity was significantly elevated in the suture-challenged vehicle-treated group (3,075 ± 1,009 pmol/mg/h) as compared to unoperated controls (464.2 ± 135 pmol/mg/h, p < 0.001). Treatment with LJP 1207 resulted in slower early phase neovascularization compared to vehicle-treated animals (not significant). At days 7-14, there was no significant difference in the extent of corneal neovascularization between inhibitor- and vehicle-treated corneas, even though inhibitor treatment caused a normalization of corneal VAP-1/SSAO activity (885 ± 452 pmol/mg/h). Our results demonstrate that the significant elevation of VAP-1/SSAO activity due to corneal injury can be prevented with VAP-1/SSAO inhibitor LJP 1207 treatment. However, normalization of VAP-1/SSAO activity in this model does not prevent the development of corneal neovascularization. PMID:23397320

  12. Lack of association between VAP-1/SSAO activity and corneal neovascularization in a rabbit model

    PubMed Central

    Markó, Katalin; Tábi, Tamás; Szökő, Éva; Zelkó, Romána; Tóth, Miklós; Petrash, J. Mark; Mátyus, Péter; Németh, János

    2014-01-01

    The aim of this study is to determine the efficacy of a potent and specific vascular adhesive protein-1/ semicarbazide-sensitive amine oxidase (VAP-1/SSAO) inhibitor, LJP 1207, as a potential antiangiogenic and anti-inflammatory agent in the therapy of corneal neovascularization. Corneal neovascularization was induced with intrastromal suturing in rabbits (n = 20). Topical treatment with VAP-1/SSAO inhibitor LJP 1207 (n = 5, 4 times a day), bevacizumab (n = 5, daily), their combination (n = 5) and vehicle only (n = 5, 4 times a day) were applied postoperatively for 2 weeks. The development and extent of corneal neovascularization were evaluated by digital image analysis. At the end of the observation period, the level of corneal and serum VAP-1/SSAO activity was measured fluorometrically and radiochemically. The corneal VAP-1/SSAO activity was significantly elevated in the suture-challenged vehicle-treated group (3,075 ± 1,009 pmol/mg/h) as compared to unoperated controls (464.2 ± 135 pmol/mg/h, p <0.001). Treatment with LJP 1207 resulted in slower early phase neovascularization compared to vehicle-treated animals (not significant). At days 7–14, there was no significant difference in the extent of corneal neovascularization between inhibitor- and vehicle-treated corneas, even though inhibitor treatment caused a normalization of corneal VAP-1/SSAO activity (885 ± 452 pmol/mg/h). Our results demonstrate that the significant elevation of VAP-1/SSAO activity due to corneal injury can be prevented with VAP-1/SSAO inhibitor LJP 1207 treatment. However, normalization of VAP-1/ SSAO activity in this model does not prevent the development of corneal neovascularization. PMID:23397320

  13. Corneal Alternations Induced by Topical Application of Benzalkonium Chloride in Rabbit

    PubMed Central

    Chen, Wensheng; Li, Zhiyuan; Hu, Jiaoyue; Zhang, Zhenhao; Chen, Lelei; Chen, Yongxiong; Liu, Zuguo

    2011-01-01

    Benzalkonium chloride (BAC) is the most common preservative in ophthalmic preparations. Here, we investigated the corneal alternations in rabbits following exposure to BAC. Twenty-four adult male New Zealand albino rabbits were randomly divided into three groups. BAC at 0.01%, 0.05%, or 0.1% was applied twice daily to one eye each of rabbits for 4 days. The contralateral untreated eyes were used as control. Aqueous tear production and fluorescein staining scores of BAC-treated eyes were compared with those of controls. The structure of the central cornea was examined by in vivo confocal microscopy. Expression of mucin-5 subtype AC (MUC5AC) in conjunctiva was detected by immunostainig on cryosections. Corneal barrier function was assessed in terms of permeability to carboxy fluorescein (CF). The distribution and expression of ZO-1, a known marker of tight junction, and reorganization of the perijunctional actomyosin ring (PAMR) were examined by immunofluorescence analysis. Although there were no significant differences between control and BAC-treated eyes in Schirmer scores, corneal fluorescein scores and the number of conjunctival MUC5AC staining cells, in vivo confocal microscopy revealed significant epithelial and stromal defects in all BAC-treated corneas. Moreover, BAC at 0.1% resulted in significant increases in central corneal thickness and endothelial CF permeability, compared with those in control eyes, and endothelial cell damage with dislocation of ZO-1 and disruption of PAMR. Topical application of BAC can quickly impair the whole cornea without occurrence of dry eye. A high concentration of BAC breaks down the barrier integrity of corneal endothelium, concomitant with the disruption of PAMR and remodeling of apical junctional complex in vivo. PMID:22022526

  14. Gamma-Irradiated Sterile Cornea for Use in Corneal Transplants in a Rabbit Model

    PubMed Central

    Yoshida, Junko; Heflin, Thomas; Zambrano, Andrea; Pan, Qing; Meng, Huan; Wang, Jiangxia; Stark, Walter J.; Daoud, Yassine J.

    2015-01-01

    Purpose: Gamma irradiated corneas in which the donor keratocytes and endothelial cells are eliminated are effective as corneal lamellar and glaucoma patch grafts. In addition, gamma irradiation causes collagen cross inking, which stiffens collagen fibrils. This study evaluated gamma irradiated corneas for use in corneal transplantations in a rabbit model comparing graft clarity, corneal neovascularization, and edema. Methods: Penetrating keratoplasty was performed on rabbits using four types of corneal grafts: Fresh cornea with endothelium, gamma irradiated cornea, cryopreserved cornea, and fresh cornea without endothelium. Slit lamp examination was performed at postoperative week (POW) one, two, and four. Corneal clarity, edema, and vascularization were graded. Confocal microscopy and histopathological evaluation were performed. A P < 0.05 was statistically significant. Results: For all postoperative examinations, the corneal clarity and edema were statistically significantly better in eyes that received fresh cornea with endothelium compared to the other three groups (P < 0.05). At POW 1, gamma irradiated cornea scored better than the cryopreserved and fresh cornea without endothelium groups in clarity (0.9 vs. 1.5 and 2.6, respectively), and edema (0.6 vs. 0.8 and 2.0, respectively). The gamma irradiated corneas, cryopreserved corneas and the fresh corneas without endothelium, developed haze and edema after POW 2. Gamma irradiated cornea remained statistically significantly clearer than cryopreserved and fresh cornea without endothelium during the observation period (P < 0.05). Histopathology indicated an absence of keratocytes in gamma irradiated cornea. Conclusion: Gamma irradiated corneas remained clearer and thinner than the cryopreserved cornea and fresh cornea without endothelium. However, this outcome is transient. Gamma irradiated corneas are useful for lamellar and patch grafts, but cannot be used for penetrating keratoplasty. PMID:26180475

  15. Choline transport in the isolated rabbit corneal epithelium

    SciTech Connect

    Faust, R.L.

    1988-01-01

    In the present study, isolated epithelial sheets were obtained by performing two sequential anterior keratectomies, three weeks apart, on rabbit corneas. Light microscopy of the isolated sheets revealed a multilayered epithelium with an intact basal cell layer without contamination from other cell types. The accumulation of ({sup 3}H)choline into the epithelial sheets was studied at substrate concentrations varying from 1 to 100 {mu}Moles with and without the addition of specific metabolic and stereochemical inhibitors. Accumulation of ({sup 3}H)choline into these sheets was saturable. Kinetic analysis, performed by estimation from double-reciprocal plots, revealed a single component system with a K{sub m} of 24.9 {mu}M. The metabolic inhibitors potassium cyanide and ouabain showed no effect on the uptake of ({sup 3}H)choline; however, the stereochemical inhibitor hemicholinium-3 significantly reduced the accumulation of radiolabel at both high and low substrate concentrations. The results suggest a non-energy dependent yet a highly specific transport system for the accumulation of choline into the rabbit epithelium.

  16. Medroxyprogesterone on corneal ulceration. Its effects after alkali burns on rabbits.

    PubMed

    Lass, J H; Campbell, R C; Rose, J; Foster, C S; Dohlman, C H

    1981-04-01

    The effect of medroxyprogesterone acetate treatment in preventing or retarding corneal ulceration after alkali burns was studied in rabbits in an attempt to correlate dose and response. The eyes were treated for 21 days with a 0.01% or 1% suspension administered topically four times a day or medroxyprogesterone acetate, 4 mg or 30 mg, given subconjunctivally on alternate days. None of these regimens was noticeably effective, although at times there was a trend toward retarding ulceration. Thus, it was not possible to confirm earlier reports of substantial efficacy of medroxyprogesterone. Corneal stroma with epithelial defects and/or ulcers persistently showed infiltration with neutrophils in the superficial stroma within the epithelial defect, implicating the tears as the source of the inflammatory cells. PMID:7224939

  17. Histopathological study of corneal flap striae following laser in situ keratomileusis in rabbits

    PubMed Central

    LIU, LI; SONG, FANG-ZHOU; BAO, LIAN-YUN

    2015-01-01

    The aim of the present study was to investigate the histopathological changes and wound healing process of rabbit corneas following conventional laser in situ keratomileusis (LASIK) with and without the complication of flap macrostriae. The right eyes of 14 rabbits underwent LASIK with the formation of flap striae (macrostriae group) and the left underwent LASIK alone (control group). Two rabbits were selected at random for sacrifice on days 1, 3, 7 and 14, and at 1, 3 and 6 months postoperatively. The histopathological characters of the corneas were compared by hematoxylin and eosin (H&E), periodic acid-Schiff (PAS) and Masson staining. In the control group, the epithelial basement membrane of the cornea exhibited microstriae and the arrangement of stromal collagen fibers was regular. The width of the microstriae in the flap was 20–40 μm one week after surgery and the microstriae were no longer visible two weeks postoperatively. In the macrostriae group, infiltration of polymorphonuclear cells occurred around the incision and irregular hyperplasia of the epithelium was observed due to undulation of the epithelial basement membrane on the first postoperative day. The collagen fibers and striae of the corneal stroma exhibited irregular undulation one month postoperatively. The area between the corneal flap and stromal bed was distinctly stained by PAS and Masson stains. Macrostriae with a width of 80–120 μm affecting two-thirds of the entire cornea remained visible six months postoperatively. In conclusion, the inflammatory reactions and clinical impact of flap macrostriae were severe. Macrostriae involving two-thirds of the entire cornea remained visible six months postoperatively. Longer-term studies are required to further elucidate the issues associated with corneal flap striae. PMID:25667649

  18. The permeability of rabbit and human corneal endothelium.

    PubMed Central

    Hodson, S; Wigham, C

    1983-01-01

    The fluxes of sodium, chloride and bicarbonate across endothelium plus stroma and then stroma alone were measured in the direction from lens-side to tear-side in rabbit and human corneas in vitro, in order to measure passive permeabilities. The results were used to calculate the permeability of the endothelium. Hodgkin's equation (1951) was then used to calculate the partial electrical conductivity of each ion crossing the endothelium. The summated electrical conductivities of sodium, chloride and bicarbonate were equal to 89 +/- 8% of the measured electrical conductivity, suggesting that the ions diffuse independently across the endothelium in the direction lens-side to tear-side. Stereological analysis of the intercellular spaces supports the idea that the ions permeate through this route and that the physical shape of the spaces determines almost entirely the permeability of the endothelial layer. Trans-endothelial sodium and chloride permeabilities are nearly equal, which may be explained by supposing the intercellular spaces include a cation exchanger of fixed negative charge capacity around 60 m-equiv l.-1 intercellular fluid. PMID:6631742

  19. Comparison of Cytotoxic Effects on Rabbit Corneal Endothelium between Preservative-free and Preservative-containing Dorzolamide/timolol

    PubMed Central

    Kwon, Junki; Heo, Jeong Hwa; Kim, Hyo Myung

    2015-01-01

    Purpose To evaluate and compare the toxic effects of eyedrops containing a fixed combination of 2.0% dorzolamide and 0.5% maleate timolol with or without preservatives on rabbit corneal endothelium. Methods This study was performed with 22 eyes of New Zealand white rabbits. Dorzolamide/timolol eyedrops with preservative (Cosopt group) or without preservative (Cosopt-S group) were diluted with a balanced salt solution at a 1 : 1 ratio. We injected 0.1 mL of diluted Cosopt into the anterior chamber of left eyes and an equal volume of diluted Cosopt-S into the anterior chamber of right eyes. Corneal thickness, corneal haze, and conjunctival injection were measured before and 24 hours after treatment. Endothelial damage was compared between both eyes by vital staining (alizarin red/trypan blue staining), live/dead cell assay, TUNEL assay, and scanning electron microscopy. Results Corneal endothelial damage was severe in the Cosopt group. Cosopt-treated eyes exhibited remarkable corneal edema and prominent apoptosis of endothelial cells. In addition, the live/dead cell assay revealed many dead cells in the endothelium, and scanning electron microscopy analysis showed that corneal endothelial cells exhibited a partial loss of microvilli on the surface as well as extensive destruction of intercellular junctions. However, in the Cosopt-S group, corneal edema was mild and the damage to the corneal endothelium was minimal. Conclusions The main cause of corneal endothelial toxicity was due to the preservative in the dorzolamide/timolol fixed combination eyedrops, and not the active ingredient. Thus, it appears to be safer to use preservative-free eyedrops during the early postoperative period. PMID:26457041

  20. Activity of matrix metalloproteinases 2 and 9 in cultured rabbit corneal epithelium cells stimulated by tumor necrosis factor alpha.

    PubMed

    Wu, Z-Q; Zhang, Z-L; Nie, S-W; Yuan, J; Yang, Y-N

    2015-01-01

    We studied the activity of matrix metalloproteinases (MMP) 2 and 9 generated by cultured rabbit corneal epithelium cells that had been stimulated with tumor necrosis factor alpha (TNF-α), to investigate the possible regulative mechanisms of MMP-2/9 and their potential effect on corneal inflammatory diseases. The rabbit corneal epithelium cells were cultured in vitro and incubated with different concentrations of TNF-α (0, 1, 10, and 100 ng/mL) for 24 h. The activity of MMP-2/9 was examined using gelatin zymography. The results were analyzed by computer image analysis and statistical tests. TNF-α stimulated the secretion of MMP-2/9 in a dose-dependent manner, and MMP-2 was activated by TNF-α. Inflammatory factors such as TNF-α can stimulate MMP-2/9 activity in corneal epithelium cells. This may be a potential manipulating mechanism of MMP expression in the pathogenesis of corneal diseases, and could play an important role in the prevention and treatment of corneal inflammatory diseases. PMID:26125840

  1. Repeatability and Reproducibility of Corneal Biometric Measurements Using the Visante Omni and a Rabbit Experimental Model of Post-Surgical Corneal Ectasia

    PubMed Central

    Liu, Yu-Chi; Konstantopoulos, Aris; Riau, Andri K.; Bhayani, Raj; Lwin, Nyein C.; Teo, Ericia Pei Wen; Yam, Gary Hin Fai; Mehta, Jodhbir S.

    2015-01-01

    Purpose: To investigate the repeatability and reproducibility of the Visante Omni topography in obtaining topography measurements of rabbit corneas and to develop a post-surgical model of corneal ectasia. Methods: Eight rabbits were used to study the repeatability and reproducibility by assessing the intra- and interobserver bias and limits of agreement. Another nine rabbits underwent different diopters (D) of laser in situ keratosmileusis (LASIK) were used for the development of ectasia model. All eyes were examined with the Visante Omni, and corneal ultrastructure were evaluated with transmission electron microscopy (TEM). Results: There was no significant intra- or interobserver difference for mean steep and flat keratometry (K) values of simulated K, anterior, and posterior elevation measurements. Eyes underwent −5 D LASIK had a significant increase in mean amplitude of astigmatism and posterior surface elevation with time (P for trend < 0.05). At 2 and 3 months, the −5 D LASIK group had significant greater mean amplitude of astigmatism (P = 0.036; P = 0.027) and posterior surface elevation (both P < 0.005) compared with control group. On TEM, the mean collagen fibril diameter and interfibril distance in the −5 D LASIK eyes were significantly greater than in controls at 3 months (P = 0.018; P < 0.001). Conclusions: The Visante Omni provided imaging of the rabbit cornea with good repeatability and reproducibility. Application of −5 D LASIK treatment produced a rabbit model of corneal ectasia that was gradual in development and simulated the human condition. Translational Relevance: The results provide the foundations for the future evaluation of novel treatment modalities for post-surgical ectasia and keratoconus. PMID:25938004

  2. High osmotic pressure increases reactive oxygen species generation in rabbit corneal epithelial cells by endoplasmic reticulum

    PubMed Central

    Wang, Peng; Sheng, Minjie; Li, Bing; Jiang, Yaping; Chen, Yihui

    2016-01-01

    Tear high osmotic pressure (HOP) has been recognized as the core mechanism underlying ocular surface inflammation, injury and symptoms and is closely associated with many ocular surface diseases, especially dry eye. The endoplasmic reticulum (ER) is a multi-functional organelle responsible for protein synthesis, folding and transport, biological synthesis of lipids, vesicle transport and intracellular calcium storage. Accumulation of unfolded proteins and imbalance of calcium ion in the ER would induce ER stress and protective unfolded protein response (UPR). Many studies have demonstrated that ER stress can induce cell apoptosis. However, the association between tear HOP and ER stress has not been studied systematically. In the present study, rabbit corneal epithelial cells were treated with HOP and results showed that the production of reactive oxygen species increased markedly, which further activated the ER signaling pathway and ultimately induced cell apoptosis. These findings shed new lights on the pathogenesis and clinical treatment of dry eye and other ocular surface diseases. PMID:27158374

  3. Dynamic OCT measurements of corneal biomechanical properties after UV cross-linking in the rabbit

    NASA Astrophysics Data System (ADS)

    Twa, Michael D.; Li, Jiasong; Manapuram, Ravi K.; Menodiado, Floredes M.; Singh, Manmohan; Aglyamov, Salavat; Emelianov, Stanislav; Larin, Kirill V.

    2013-03-01

    Structural properties of the cornea determine the shape and optical quality of the eye. Keratoconus, a structural degeneration of the cornea, is often treated with UV-induced collagen cross-linking to increase tissue resistance to further deformation and degeneration. Optimal treatments would be customized to the individual and consider preexisting structural properties as well as the effects induced by treatment and this requires the capability to noninvasively measure tissue properties. The purpose of this study is to use novel methods of optical elastography to study the effects of UV-induced corneal collagen cross-linking in the rabbit eye. Low-amplitude (<1μm) elastic flexural waves were generated using focused air-pulse stimulation. Elastic wave propagation was measured over a 10x10mm area using Phase Stabilized Swept Source Optical Coherence Elastography (PhS-SSOCE) with a sensitivity of ~ 10 nm. Wave amplitude and velocity were computed and compared in tissues before and after UV cross-linking. Wave amplitude was decreased by the cross-linking treatment, while wave velocity was greater in cross-linked tissue than it was in the untreated cornea. Decreased wave amplitude and increased wave velocity after cross-linking is consistent with increased tissue stiffness. This was confirmed by conventional mechanical tension testing. These results demonstrate that the combination of the PhS-SSOCE and focused air pulse stimulation is capable of measuring low amplitude tissue motion and quantifying corneal stiffness.

  4. Human corneal stromal stem cells support limbal epithelial cells cultured on RAFT tissue equivalents

    PubMed Central

    Kureshi, Alvena K; Dziasko, Marc; Funderburgh, James L; Daniels, Julie T

    2015-01-01

    Human limbal epithelial cells (HLE) and corneal stromal stem cells (CSSC) reside in close proximity in vivo in the corneal limbal stem cell niche. However, HLE are typically cultured in vitro without supporting niche cells. Here, we re-create the cell-cell juxtaposition of the native environment in vitro, to provide a tool for investigation of epithelial-stromal cell interactions and to optimize HLE culture conditions for potential therapeutic application. RAFT (Real Architecture For 3D Tissue) tissue equivalents (TEs) were used as a 3-dimensional substrate for co-culturing HLE and CSSC. Our results demonstrate that a monolayer of HLE that maintained expression of p63α, ABCB5, CK8 and CK15 (HLE markers), formed on the surface of RAFT TEs within 13 days of culture. CSSC remained in close proximity to HLE and maintained expression of mesenchymal stem cell markers. This simple technique has a short preparation time of only 15 days with the onset of HLE layering and differentiation observed. Furthermore, co-cultivation of HLE with another niche cell type (CSSC) directly on RAFT TEs, eliminates the requirement for animal-derived feeder cells. RAFT TEs may be useful for future therapeutic delivery of multiple cell types to restore the limbal niche following ocular surface injury or disease. PMID:26531048

  5. The effect of subconjunctival bevacizumab on corneal neovascularization, inflammation and re-epithelization in a rabbit model

    PubMed Central

    Mello, Glauco Reggiani; Pizzolatti, Marcos Longo; Wasilewski, Daniel; Santhiago, Marcony R.; Budel, Vinícius; Moreira, Hamilton

    2011-01-01

    PURPOSE: To evaluate the use of subconjunctival bevacizumab on corneal neovascularization in an experimental rabbit model for its effect on vessel extension, inflammation, and corneal epithelialization. METHODS: In this prospective, randomized, blinded, experimental study, 20 rabbits were submitted to a chemical trauma with sodium hydroxide and subsequently divided into two groups. The experimental group received a subconjunctival injection of bevacizumab (0.15 m; 3.75 mg), and the control group received an injection of 0.15 ml saline solution. After 14 days, two blinded digital photograph analyses were conducted to evaluate the inflammation/diameter of the vessels according to pre-established criteria. A histopathological analysis of the cornea evaluated the state of the epithelium and the number of polymorphonuclear cells. RESULTS: A concordance analysis using Kappa's statistic showed a satisfactory level of agreement between the two blinded digital photography analyses. The neovascular vessel length was greater in the control group (p<0.01) than in the study group. However, the histopathological examination revealed no statistically significant differences between the groups in terms of the state of the epithelium and the number of polymorphonuclear cells. CONCLUSIONS: Subconjunctival bevacizumab inhibited neovascularization in the rabbit cornea. However, this drug was not effective at reducing inflammation. The drug did not induce persistent corneal epithelial defects. PMID:21915498

  6. Modulation of rabbit corneal epithelial cells fate using embryonic stem cell extract

    PubMed Central

    Zhan, Weijiao; Liu, Zhiping; Liu, Ying; Ke, Qicheng; Ding, Yuanyuan; Lu, Xiaoyan

    2010-01-01

    Purpose To develop a new culture system to cultivate differentiated autologous cells in vitro for cell therapy and tissue engineering. Methods After incubation in murine embryonic stem cell (ESC) extract for 1 h, streptolysin-O (SLO) permeabilized cells were resealed with CaCl2 and continually cultured for weeks. The morphological study was analyzed by light microscopy. Isolated colonies were selected and expanded to establish cell lines. Octamer-4 (Oct-4), stage-specific embryonic antigen-1 (SSEA-1), transformation-related protein 63 (p63), ATP-binding cassette subfamily G, member 2 (ABCG2), and cytokeratin3 (K3) were detected by indirect immunofluorescent staining. Oct-4, K3, and p63 were also detected by RT–PCR analysis. To examine the stemness characteristics of the induced cells, both alkaline phosphatase (AKP) staining and tumorigenicity detection were performed, respectively. Results Reprogramming was induced in corneal epithelial cells. The reprogrammed cells showed characteristics similar to ESCs in the early weeks, including colony formation, positive AKP staining, and multi-potential differentiation in vivo. Oct-4 and SSEA1 protein expression was upregulated. However, these changes were not persistent or stable. With the passage of time, the colonies became flat. The ESC markers were downregulated, while epithelial cell related proteins gradually increased. Conclusions Less terminal differentiated rabbit corneal epithelial cells could be induced to a more pluripotent state with embryonic stem cell extract (ESC-E). These cells have the potential to return to the beginning of their own lineage and obtain the ability of long-term growth. Our findings indicate that this culture system can generate low-immunogenic autologous cells for use in regenerative medicine. PMID:20664691

  7. Resolvin E1 analog RX-10045 0.1% reduces corneal stromal haze in rabbits when applied topically after PRK

    PubMed Central

    Torricelli, Andre A. M.; Santhanam, Abirami; Agrawal, Vandana

    2014-01-01

    Purpose To perform a masked study to determine whether resolvin E1 (RvE1), a lipid-derived immunomodulator, could regulate the development of corneal haze and opacity-related myofibroblasts after opacity-generating high correction photorefractive keratectomy (PRK) in rabbits. Methods Three groups of eight rabbits each were included in the study. Nine diopter (D) PRK for myopia was performed in each test cornea, and the eyes were treated with 30 µl of topical solution every 4 h (six times a day) for 5 days starting immediately after PRK. Group 1 was treated with 0.1% RX-10045, a prodrug of an RvE1 analog; group 2 was treated with 0.01% RX-10045; and group 3 was treated with vehicle control solution. At 1 month after PRK, haze was graded at the slit-lamp by a masked observer. Immunohistochemistry for α-smooth muscle actin (SMA) was performed on the central cornea of each test eye to determine the anterior stromal myofibroblast density. Results Corneal opacity was significantly lower in the 0.1% RX-10045 group, but not the 0.01% RX-10045 group, compared to the vehicle control group (p=0.029), at 1 month after −9.0D PRK. At 1 month after −9.0D PRK, SMA+ myofibroblast densities in the anterior stroma were not statistically significantly different among the three groups, although a trend toward lower myofibroblast generation was noted in the 0.1% RX-10045 group. Conclusions Topical 0.1% RX-10045, a prodrug of an RvE1 analog, reduces corneal opacity after haze-generating PRK in rabbits. Further studies are needed to determine the precise points at which RvE1 decreases corneal opacity after injury. PMID:25558174

  8. Effect of sertraline on Ca²⁺ fluxes in rabbit corneal epithelial cells.

    PubMed

    Yeh, Jeng-Hsien; Sun, Te-Kung; Chou, Chiang-Ting; Chen, Wei-Chuan; Lee, Jenn-Kuen; Yeh, Hsiao-Chun; Liang, Wei-Zhe; Kuo, Chun-Chi; Shieh, Pochuen; Kuo, Daih-Huang; Jan, Chung-Ren

    2015-04-30

    The effect of sertraline, a selective serotonin reuptake inhibitor (SSRI), on cytosolic free Ca²⁺ concentrations ([Ca²⁺](i)) in a rabbit corneal epithelial cell line (SIRC) is unclear. This study explored whether sertraline changed basal [Ca²⁺](i) levels in suspended SIRC cells by using fura-2 as a Ca²⁺-sensitive fluorescent dye. Sertraline at concentrations between 10-100 μM increased [Ca²⁺](i) in a concentration-dependent manner. The Ca²⁺ signal was reduced by 23% by removing extracellular Ca²⁺. Sertraline induced Mn²⁺ influx, leading to quench of fura-2 fluorescence, suggesting Ca²⁺ influx. This Ca²⁺ influx was inhibited by phospholipase A₂ inhibitor aristolochic acid, but not by store-operated Ca²⁺ channel blockers and protein kinase C/A modulators. In Ca²⁺-free medium, pretreatment with the endoplasmic reticulum Ca²⁺ pump inhibitor thapsigargin, cyclopiazonic acid or 2,5-di-tert-butylhydroquinone greatly inhibited sertraline-induced Ca²⁺ release. Inhibition of phospholipase C with U73122 abolished sertraline-induced [Ca²⁺](i) rise. At concentrations of 5-50 μM, sertraline killed cells in a concentration-dependent manner. The cytotoxic effect of 25 μM sertraline was not reversed by prechelating cytosolic Ca²⁺ with BAPTA/AM. Collectively, in SIRC cells, sertraline induced [Ca²⁺](i) rises by causing phospholipase C-dependent Ca²⁺ release from the endoplasmic reticulum and Ca²⁺ influx via phospholipase A₂-sensitive Ca²⁺ channels. Sertraline-caused cytotoxicity was mediated by Ca²⁺-independent pathways. PMID:25858469

  9. Mesenchymal–epithelial cell interactions and proteoglycan matrix composition in the presumptive stem cell niche of the rabbit corneal limbus

    PubMed Central

    Yamada, Keiko; Young, Robert D.; Lewis, Philip N.; Shinomiya, Katsuhiko; Meek, Keith M.; Kinoshita, Shigeru; Caterson, Bruce

    2015-01-01

    Purpose To investigate whether mesenchymal–epithelial cell interactions, similar to those described in the limbal stem cell niche in transplant-expired human eye bank corneas, exist in freshly enucleated rabbit eyes and to identify matrix molecules in the anterior limbal stroma that might have the potential to help maintain the stem cell niche. Methods Fresh limbal corneal tissue from adult Japanese white rabbits was obtained and examined in semithin resin sections with light microscopy, in ultrathin sections with transmission electron microscopy, and in three-dimensional (3D) reconstructions from data sets of up to 1,000 serial images from serial block face scanning electron microscopy. Immunofluorescence microscopy with five monoclonal antibodies was used to detect specific sulfation motifs on chondroitin sulfate glycosaminoglycans, previously identified in association with progenitor cells and their matrix in cartilage tissue. Results In the rabbit limbal cornea, while no palisades of Vogt were present, the basal epithelial cells stained differentially with Toluidine blue, and extended lobed protrusions proximally into the stoma, which were associated with interruptions of the basal lamina. Elongate processes of the mesenchymal cells in the superficial vascularized stroma formed direct contact with the basal lamina and basal epithelial cells. From a panel of antibodies that recognize native, sulfated chondroitin sulfate structures, one (6-C-3) gave a positive signal restricted to the region of the mesenchymal–epithelial cell associations. Conclusions This study showed interactions between basal epithelial cells and subjacent mesenchymal cells in the rabbit corneal limbus, similar to those that have been observed in the human stem cell niche. A native sulfation epitope in chondroitin sulfate glycosaminoglycans exhibits a distribution specific to the connective tissue matrix of this putative stem/progenitor cell niche. PMID:26788025

  10. High MMP-9 Expression May Contribute to Retroprosthetic Membrane Formation after KPro Implantation in Rabbit Corneal Alkali Burn Model

    PubMed Central

    Gao, Minghong; Sang, Wei; Liu, Fuying; Yu, Hai; Zhou, Runhai; Belin, Michael Wellington; Zloty, Peter; Chen, Yingxin

    2016-01-01

    Purpose. To evaluate aqueous humor MMP-9 levels in alkali-burned rabbit cornea following KPr implantation and their roles in RPMs formation. Methods. Left eyes of 36 rabbits received a deep corneal alkali wound. 12 corneas were implanted with KPro and the other 24 control corneas were either penetrating keratoplasty or left without keratoplasty. Aqueous humor MMP-9 and TIMP-1 levels were determined and RPMs were obtained for histopathological and ultrastructural examination. Results. Alkali exposure induced significant increase in aqueous humor MMP-9 level and the data were further enhanced by KPro implantation. By contrast, TMIP-1 levels in aqueous humor showed a decreased trend following corneal alkali burn and KPro surgery. RPMs were developed in 5 out of 10 cases of KPro successfully implanted eyes. Histopathology showed the presence of a large number of fibroblasts and collagen fibers arranged irregularly with inflammatory cells infiltration, and an ingrowth of new blood vessels in this retrokeratoprosthesis fibrous tissue. Immunohistochemical analysis showed positive stain of RPMs for both MMP-9 and TIMP-1. Aqueous humor MMP-9 levels were significantly higher in RPM group postoperatively, while TIMP-1 levels were comparatively lower than that of No-RPM group. Conclusions. Our study evidenced the potential pathophysiological role of MMP-9 expression in RPM formation following KPro implantation. PMID:26949542

  11. Bone Marrow Mesenchymal Stem Cell Transplantation in a Rabbit Corneal Alkali Burn Model (A Histological and Immune Histo-chemical Study)

    PubMed Central

    Ahmed, Soheir Kamal; Soliman, Amel Ali; Omar, Sahar M. M.; Mohammed, Wafaa Rabee

    2015-01-01

    Background Alkali-burned corneas can seldom heal properly to restore corneal transparency. Treatment of this severe disorder of the ocular surface remains a challenge. Aim of the Work was to investigate whether systemically transplanted bone marrow mesenchymal stem cells (BM-MSCs) can promote corneal wound healing after alkali burn. Material and Methods Thirty five male New Zealand rabbits were used in this study. The animals were divided into three groups. Group I; the control group was sham operated. Group II; corneal alkali burn was created. Group III; underwent corneal alkali burn then treated with BM-MSCs. All corneas were collected after fourteen and twenty eight days. Evaluation using H&E, PAS & alkaline phosphatase reaction was carried out. Immune histo-chemical staining for CD44 and vimentin was performed as well. Results the corneal epithelium of (Group II) showed marked alterations. Vascularization, cellular infiltration and irregularity of the collagen fibers were also seen in the substantia propria. Increase in the thickness of the Descemet’s membrane was noticed as well. On the other hand, at the time of 28 days, Group III rabbits showed best histological results with nearly healed corneas compared to other groups. Meanwhile, vimentin was more strongly expressed in Group III assessing the differentiating ability of BM-MSCs. Conclusion BM-MSCs could effectively promote corneal alkali burn healing. PMID:26019756

  12. A histological study of rabbit corneas after transepithelial corneal crosslinking using partial epithelial photoablation or ethanol treatment

    PubMed Central

    Ozmen, Mehmet Cuneyt; Hondur, Ahmet; Yilmaz, Guldal; Bilgihan, Kamil; Hasanreisoglu, Berati

    2014-01-01

    AIM To evaluate the histological changes after transepithelial corneal crosslinking (CXL) using partial thickness excimer laser ablation or epithelial ethanol application in an experimental rabbit study. METHODS Right eyes of twenty-four rabbits were studied. Four eyes received total epithelial debridement (group I). Four eyes received partial thickness epithelial ablation with excimer laser (group II). Twelve eyes were treated with different durations (30s and 60s) and concentrations (18% to 48%) of ethanol (group III). Riboflavin was applied for 30min intervals along with topical proparacaine drops with benzalkonium chloride, and 370 nm irradiation was performed for 30min, while riboflavin was instilled every 3min. Four eyes (group IV) received 48% ethanol for 30s without riboflavin and irradiation. Eyes were collected after 24h and examined histologically. RESULTS All eyes in group I showed keratocyte loss in the superficial 300 µ of corneal storma. In group II, 1-4 layers of epithelium were preserved and no keratocyte loss occurred. In group III, CXL after treatment with ethanol up to 24% concentration and up to 60s revealed no keratocyte loss. CXL after treatment with 48% and higher ethanol concentrations yielded keratocyte loss in the superficial 200 µ to 300 µ of cornea. CONCLUSION Incomplete excimer laser ablation of the epithelium or treatment with ethanol up to 24% concentration and up to 60s duration yielded no stromal keratocyte loss. To get the same histological appearance seen in epithelial debridement group, partial thickness excimer laser epithelial ablation or ethanol application is not adequate for transepithelial CXL. PMID:25540746

  13. Corneal recovery in a rabbit limbal stem cell deficiency model by autologous grafts of tertiary outgrowths from cultivated limbal biopsy explants

    PubMed Central

    Durak, Ismet; Gürdal, Mehmet; Baysal, Kemal; Ates, Halil; Ozbek, Zeynep; Wang, Zheng; Wu, Albert; Wolosin, J. Mario

    2016-01-01

    Purpose To determine the corneal regenerative capacity of sequentially generated primary, secondary, and tertiary limbal explant outgrowths in a limbal stem cell deficiency (LSCD) surgical model. Methods Two-millimeter-long limbal shallow biopsies were surgically excised from the upper quadrant of the right eye of rabbits and set on preserved amniotic membrane for explant culture. After the generation of primary outgrowth, the biopsies were sequentially transferred to new amniotic membrane to generate secondary and then tertiary outgrowths. Eighteen rabbits were subjected to a 360° limbal peritomy extending into the scleral zone and combined with superficial keratectomy of the corneal periphery and thorough mechanical debridement of the central cornea in their left eye. Right eye outgrowths, six of each generation, were engrafted on the ocular surface. Clinical outcomes (neovascularization, corneal clarity, and corneal fluorescein staining) were graded after 6 months. Post-mortem corneas were compared with histology, immunochemistry for p63 and Krt3, ABCG2-dependent dye exclusion, and capacity for outgrowths in explant culture. Results Immunohistology and western blot of the outgrowths for p63 and Krt3 indicated no differences in expression between the primary and tertiary outgrowths for these two markers of growth and differentiation. Clinically, all rabbits treated with amniotic membrane alone developed severe LSCD. Most rabbits grafted with cell outgrowths from all three outgrowth generations achieved stable (>6 months) recovery of the ocular surface. There were partial failures of grafts performed with two secondary and tertiary outgrowths. However, Kruskal–Wallis statistical analysis of the clinical scores yielded no significant difference between the three groups (p=0.524). Histology showed full anatomic recovery of grafts made with primary and tertiary outgrowths. Krt3 and p63 expression throughout the whole limbal corneal epithelium with primary or

  14. Transfer of mesenchymal stem cells and cyclosporine A on alkali-injured rabbit cornea using nanofiber scaffolds strongly reduces corneal neovascularization and scar formation.

    PubMed

    Cejka, Cestmir; Cejkova, Jitka; Trosan, Peter; Zajicova, Alena; Sykova, Eva; Holan, Vladimir

    2016-09-01

    The aim of this study was to examine whether nanofiber scaffolds seeded with rabbit bone marrow mesenchymal stem cells (MSCs nanofibers) transferred onto the damaged corneal surface and covered with cyclosporine A (CsA)-loaded nanofiber scaffolds (CsA nanofibers) enable healing of the rabbit cornea injured with 1N NaOH. The healing of damaged corneas was examined morphologically, immunohistochemically and biochemically on day 24 after the injury. Compared to untreated injured corneas, where corneal ulceration or large corneal thinning or even perforation were developed, injured corneas treated with drug free nanofibers healed without profound disturbances in a majority of cases, although with fibrosis and scar formation. In injured corneas treated with CsA nanofibers or MSCs nanofibers, the development of scar formation was reduced. Best healing results were obtained with a combination of MSCs and CsA nanofibers (MSCs-CsA nanofibers). Corneas healed with highly restored transparency. Neovascularization highly expressed in untreated injured corneas and reduced in corneas treated with CsA nanofibers or MSCs nanofibers, was suppressed in corneas treated with MSCs-CsA nanofibers. The levels of matrix metalloproteinase 9, inducible nitric oxide synthase, interleukin 6, α-smooth muscle actin, tumor growth factor β and vascular endothelial growth factor were significantly decreased in these corneas as compared to untreated corneas, where the levels of the above mentioned markers were high. In conclusion, MSCs-CsA nanofibers were effective in the treatment of severe alkali-induced corneal injury. PMID:26797822

  15. The Effect of Riboflavin/UVA Collagen Cross-linking Therapy on the Structure and Hydrodynamic Behaviour of the Ungulate and Rabbit Corneal Stroma

    PubMed Central

    Hayes, Sally; Kamma-Lorger, Christina S.; Boote, Craig; Young, Robert D.; Quantock, Andrew J.; Rost, Anika; Khatib, Yasmeen; Harris, Jonathan; Yagi, Naoto; Terrill, Nicholas; Meek, Keith M.

    2013-01-01

    Purpose To examine the effect of riboflavin/UVA corneal crosslinking on stromal ultrastructure and hydrodynamic behaviour. Methods One hundred and seventeen enucleated ungulate eyes (112 pig and 5 sheep) and 3 pairs of rabbit eyes, with corneal epithelium removed, were divided into four treatment groups: Group 1 (28 pig, 2 sheep and 3 rabbits) were untreated; Group 2 (24 pig) were exposed to UVA light (3.04 mW/cm2) for 30 minutes and Group 3 (29 pig) and Group 4 (31 pig, 3 sheep and 3 rabbits) had riboflavin eye drops applied to the corneal surface every 5 minutes for 35 minutes. Five minutes after the initial riboflavin instillation, the corneas in Group 4 experienced a 30 minute exposure to UVA light (3.04 mW/cm2). X-ray scattering was used to obtain measurements of collagen interfibrillar spacing, spatial order, fibril diameter, D-periodicity and intermolecular spacing throughout the whole tissue thickness and as a function of tissue depth in the treated and untreated corneas. The effect of each treatment on the hydrodynamic behaviour of the cornea (its ability to swell in saline solution) and its resistance to enzymatic digestion were assessed using in vitro laboratory techniques. Results Corneal thickness decreased significantly following riboflavin application (p<0.01) and also to a lesser extent after UVA exposure (p<0.05). With the exception of the spatial order factor, which was higher in Group 4 than Group 1 (p<0.01), all other measured collagen parameters were unaltered by cross-linking, even within the most anterior 300 microns of the cornea. The cross-linking treatment had no effect on the hydrodynamic behaviour of the cornea but did cause a significant increase in its resistance to enzymatic digestion. Conclusions It seems likely that cross-links formed during riboflavin/UVA therapy occur predominantly at the collagen fibril surface and in the protein network surrounding the collagen. PMID:23349690

  16. Short-term effects of extremely low-frequency pulsed electromagnetic field and pulsed low-level laser therapy on rabbit model of corneal alkali burn.

    PubMed

    Rezaei Kanavi, Mozhgan; Tabeie, Faraj; Sahebjam, Farzin; Poursani, Nima; Jahanbakhsh, Nazanin; Paymanpour, Pouya; AfsarAski, Sasha

    2016-04-01

    This study was conducted to investigate the effect of combining extremely low frequency-pulsed electromagnetic field (ELF-PEMF) and low-level laser therapy (LLLT) on alkali-burned rabbit corneas. Fifty alkali-burned corneas of 50 rabbits were categorized into five groups: ELF-PEMF therapy with 2 mT intensity (ELF 2) for 2 h daily; LLLT for 30 min twice daily; combined ELF-PEMF and LLLT (ELF + LLLT); medical therapy (MT); and control (i.e., no treatment). Clinical examination and digital photography of the corneas were performed on days 0, 2, 7, and 14. After euthanizing the rabbits, the affected eyes were evaluated by histopathology. The clinical and histopathologic results were compared between the groups. On days 7 and 14, no significant difference in the corneal defect area was evident between the ELF, LLLT, ELF + LLLT, and MT groups. Excluding the controls, none of the study groups demonstrated a significant corneal neovascularization in both routine histopathology and immunohistochemistry for CD31. Keratocyte loss was significantly higher in the MT group than in the ELF, LLLT, and ELF + LLLT groups. Moderate to severe stromal inflammation in the LLLT group was comparable with that in the MT group and was significantly lower than that in the other groups. In conclusion, combining LLLT and ELF was not superior to ELF alone or LLLT alone in healing corneal alkali burns. However, given the lower intensity of corneal inflammation and the lower rate of keratocytes loss with LLLT, this treatment may be superior to other proposed treatment modalities for healing alkali-burned corneas. PMID:26795389

  17. Conjunctival and corneal reactions in rabbits following short- and repeated exposure to preservative-free tafluprost, commercially available latanoprost and 0.02% benzalkonium chloride

    PubMed Central

    Liang, H; Baudouin, C; Pauly, A; Brignole-Baudouin, F

    2008-01-01

    Aim: To compare the conjunctival and corneal reactions of commercially available solution of latanoprost (Xalatan) and preservative-free (PF) tafluprost in rabbits. Methods: The rabbits received 50 μl of phosphate-buffered saline (PBS), PF-tafluprost 0.0015%, latanoprost 0.005% or benzalkonium chloride (BAK) 0.02%; all solutions were applied at 5 min intervals for a total of 15 times. The ocular surface toxicity was investigated using slit-lamp biomicroscopy examination, flow cytometry (FCM) and on imprints for CD45 and tumour necrosis factor-receptor 1 (TNFR1) conjunctival impression cytology (CIC) and corneal in vivo confocal microscopy (IVCM). Standard immunohistology also assessed inflammatory/apoptotic cells. Results: Clinical observation and IVCM images showed the highest ocular surface toxicity with latanoprost and BAK, while PF-tafluprost and PBS eyes presented almost normal corneoconjunctival aspects. FCM showed a higher expression of CD45+ and TNFR1+ in latanoprost- or BAK-instilled groups, compared with PF-tafluprost and PBS groups. Latanoprost induced fewer positive cells for inflammatory marker expressions in CIC specimens compared with BAK-alone, both of which were higher than with PF-tafluprost or PBS. Immunohistology showed the same tendency of toxic ranking. Conclusion: The authors confirm that rabbit corneoconjunctival surfaces presented a better tolerance when treated with PF-tafluprost compared with commercially available latanoprost or BAK solution. PMID:18723745

  18. Effects of hydroxypyridine derivatives mexidol and emoxypin on the reparative processes in rabbit eye on the models of corneal epithelial defect and conjunctival ischemia.

    PubMed

    Chesnokova, N B; Beznos, O V; Pavlenko, T A; Zabozlaev, A A; Pavlova, M V

    2015-01-01

    Deepithelialization of the cornea (diameter 7 mm) was performed in rabbits and the rate of defect epithelialization was evaluated. Conjunctival ischemia was modeled by application of graduated alkaline burn. Antioxidant activity and content of nitrates and nitrites was measured in the tear fluid before and after burn by chemiluminescence and Griess methods, respectively. Emoxypin and mexidol promoted healing of corneal epithelial defect at the stage of epitheliocyte migration to the defect area and at the stage of their proliferation, respectively. After treatment with both agents, the area of conjunctival ischemia decreased more rapidly, but the efficiency of mexidol was higher. Antioxidant activity and content of products of NO metabolism in tear fluid decreased after burn. Mexidol, but not emoxypin, increased these parameters. Thus, mexidol and emoxypin have different effects on corneal epithelialization and conjunctival ischemia and effects of mexidol are more pronounced. PMID:25573366

  19. Changes in cell surface primary cilia and microvilli concurrent with measurements of fluid flow across the rabbit corneal endothelium ex vivo.

    PubMed

    Doughty, M J

    1998-12-01

    Primary cilia and microvilli have been reported on the mammalian rabbit corneal endothelium but their relationship to cell function is undefined. Six corneas from healthy 2 kg female albino rabbits were glutaraldehyde-fixed post mortem (15:00 h) or twelve corneal stroma-endothelial preparations incubated at 37 degrees C under an applied hydrostatic pressure of 20 cm H2O for 4 h prior to fixation. The corneal endothelium was assessed by quantitative scanning electron microscopy. Cells fixed immediately post mortem were decorated with small stubby microvilli (average 21 +/- 13/100 micron 2), and only 25% of the cells were decorated with primary cilia having an average length of 2.44 +/- 1.56 microns. Following 4 h ex vivo incubation with a phosphate-buffered Ringer solution, conspicuous microvilli developed to an average density of 40 +/- 19/100 micron 2 and primary cilia were found on 12% of the cells, having on average length of 2.27 +/- 1.38 microns. Following 4 h incubation in a bicarbonate-buffered Ringer solution, small stubby microvilli developed to a density of 49 +/- 18/100 micron 2, and 40% of the cells showed primary cilia with an average length of 4.31 +/- 1.93 microns; the net trans-endothelial fluid flow in the latter set was 60% greater. These studies indicate that the primary cilia on corneal endothelial cells might be responsive to fluid flow, but that mild mechanical and/or chemical stress could also be the cause of the change since the elaboration of primary cilia can be accompanied by microvilli as well. PMID:10036788

  20. Analysis of gene regulation in rabbit corneal epithelial cells induced by ultraviolet radiation.

    PubMed

    Stevens, Jacqueline J; Rogers, Christian; Howard, Carolyn B; Moore, Caronda; Chan, Lai-Man

    2005-04-01

    Ultraviolet (UV)-induced cataracts are becoming a major environmental health concern because of the possible decrease in the stratospheric ozone layer. Experiments were designed to isolate gene(s) affected by UV irradiation in rabbit cornea tissues using fluorescent differential display-reverse transcription-polymerase chain reaction (FDDRT-PCR). The epithelial cells were grown in standard medium for 2 or 4 hours post treatment. Cornea epithelial cells were irradiated with UVB for 20 minutes. RNA was extracted and amplified by reverse transcriptase-polymerase chain reaction using poly A+ specific anchoring primers and random arbitrary primers. Polyacrylamide gel electrophoresis revealed several differentially expressed genes in untreated versus UV irradiated cells. Complimentary DNA (cDNA) fragments resulting from fluorescent differentially expressed mRNAs were eluted from the gel and re-amplified. The re-amplified PCR products were cloned directly into the PCR-TRAP cloning system. These data showed that FDDRT-PCR is a useful technique to elucidate UV-regulated gene expressions. Future experiments will involve sequence analysis of cloned inserts. The identification of these genes through sequence analysis could lead to a better understanding of cataract formation via DNA damage and mechanisms of prevention. PMID:16705801

  1. High resolution scanning electron microscopy of rabbit corneal endothelium to show effects of UV-visible irradiation in the presence of chlorpromazine

    SciTech Connect

    Lea, P.J.; Hollenberg, M.J.; Menon, I.A.; Temkin, R.J.; Persad, S.D.; Basu, P.K. )

    1989-01-01

    The ultrastructure of rabbit cornea endothelial cells was examined by scanning electron microscopy (SEM) in freeze-cleaved corneas using a Hitachi S-570 scanning electron microscope in the high resolution mode (HRSEM). In order to study phototoxic effects in vitro, rabbit corneas (experimental) were cultured as organ culture in the presence of 5 micrograms/ml chlorpromazine (CPZ) and irradiated. For comparison, control 1 corneas were not irradiated but incubated in the dark without CPZ in the medium; control 2 corneas were also kept in the dark but in the presence of CPZ; control 3 corneas were irradiated with no CPZ in the medium. Cellular damage was not seen in the three types of control corneas, but in the experimental corneas the endothelial cells showed extensive disruption of the cell membrane and some deterioration of the intracellular components. Our study confirmed that HRSEM is a satisfactory new technique for visualizing damage of the intracellular organelles of corneal endothelium.

  2. A novel method in preparation of acellularporcine corneal stroma tissue for lamellar keratoplasty

    PubMed Central

    Shao, Yi; Tang, Jing; Zhou, Yueping; Qu, Yangluowa; He, Hui; Liu, Qiuping; Tan, Gang; Li, Wei; Liu, Zuguo

    2015-01-01

    Our objective was to develop a novel lamellar cornealbiomaterial for corneal reconstruction.Theporcine acellular corneal stroma discs (ACSDs) were prepared from de-epithelized fresh porcine corneas (DFPCs) by incubation with 100% fresh human serum and additional electrophoresis at 4°C. Such manipulation removed theanterior corneal stromal cells without residual of DNA content and α-Galantigen. Human serum decellularizing activity on porcineanterior corneal stroma cells is through apoptosis, and associated with the presence of α-Gal epitopes in anterior stroma. ACSDs displayed similar optical, biomechanical properties and ultrastructure to DFPCs, and showed good histocompatibility in rabbit corneal stromal pockets and anterior chamber. Rabbit corneallamellar keratoplasty (LKP) using ACSDs showed no rejection and high transparency of cornea at 2 months after surgery. In vivo confocal laser scanning microscopy and immunostaining analysis showed complete re-epithelization and stromal cell in growth of ACSDs without inflammatory cell infiltration, new blood vessel ingrowth and excessive wound healing. In conclusion, this novel decellularization method may be valuable for preparation of xenogenic corneal tissue for clinical application, ACSDs resulted from this method may be served as a matrix equivalent for LKP in corneal xenotransplantation. PMID:26885261

  3. Augmented anti-angiogenesis activity of polysulfated heparin-endostatin and polyethylene glycol-endostatin in alkali burn-induced corneal ulcers in rabbits

    PubMed Central

    LI, ZHAO-NA; YUAN, ZHONG-FANG; MU, GUO-YING; HU, MING; CAO, LI-JUN; ZHANG, YA-LI; GE, MING-XU

    2015-01-01

    Endostatin (ES) is an endogenous angiogenesis inhibitor that has the ability to inhibit tumor growth and metastasis. However, its clinical application is limited by a number of disadvantages, such as poor stability, short half-life and the requirement of high doses to maintain its efficacy. The chemical modification on ES may offer a solution to these disadvantages. The aim of the present study was to evaluate the effects of ES, polysulfated heparin-endostatin (PSH-ES) and polyethylene glycol-endostatin (PEG-ES) on the endothelial cell proliferation and angiogenesis associated with corneal neovascularization (CNV) and to determine their mechanisms of action. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) was used to study the effects of ES and its derivatives on endothelial cell proliferation in vitro, and rabbits were used to evaluate the effects of ES and its derivatives on CNV in vivo. In the evaluation of CNV, the expression of vascular endothelial growth factor in the cornea was measured via immunohistochemistry and microvessels were counted. ES and its derivatives significantly inhibited endothelial cell proliferation in vitro (P<0.05) and suppressed CNV in vivo. Among the compounds examined, ES most effectively inhibited endothelial cell proliferation in vitro (P<0.05); however, PSH-ES and PEG-ES most effectively inhibited CNV in vivo (P<0.05). These results indicate that PSH-ES and PEG-ES are candidate anti-angiogenesis drugs. PMID:26622410

  4. Corneal Disorders

    MedlinePlus

    ... Injuries Dystrophies - conditions in which parts of the cornea lose clarity due to a buildup of cloudy material Treatments of corneal disorders include medicines, corneal transplantation, and corneal laser surgery. NIH: National Eye Institute

  5. Rabbit corneal and conjunctival permeability of the novel aldose reductase inhibitors: N-[[4-(benzoylamino)phenyl] sulphonyl]glycines and N-benzoyl-N-phenylglycines.

    PubMed

    Kompella, U B; Sunkara, G; Thomas, E; Clark, C R; Deruiter, J

    1999-08-01

    Corneal and conjunctival permeability has been investigated for novel aldose reductase inhibitors (ARIs) of the N{[4-(benzoylamino)phenyl]sulphonyl}glycine (benzoylaminophenylsulphonylglycine) and N-benzoyl-N-phenylglycine (benzoylphenylglycine) series, compounds developed for prevention of cataract formation in diabetic subjects. Six benzoylaminophenylsulphonylglycines were synthesized with modifications either of the phenyl group or of the glycine structure and three benzoylphenylglycines were synthesized with modification in the phenyl group of the benzoyl moiety. Transport of ARIs in the mucosal to serosal direction was evaluated across rabbit cornea and conjunctiva bathed in glutathione-bicarbonate Ringer's solution maintained at pH 7.4 and 37 degrees C. The permeability coefficients of the novel ARIs across cornea and conjunctiva ranged from 1.87 to 8.95 x 10(-6) cm s(-1) and from 4.6 to 19.15 x 10(-6) cm s(-1), respectively. The ratio of corneal to conjunctival permeability ranged from 0.12 to 0.79. The calculated log partition coefficient (log P) values for the ARIs were in the range 0.84 to 2.78. The log distribution coefficients (log D) were in the range -2.87 to -0.89. There was no apparent relationship between log P or log D and the permeability coefficients of the ARIs for either tissue. Cornea was more resistant to ARI transport than was conjunctiva. Substitution of a phenyl group for hydrogen in the glycine methylene group reduced the permeability coefficient. Permeability coefficients were different for different stereoisomers. Compared with the permeability coefficient of benzoylaminophenylsulphonylglycine, that of 4-fluorobenzoylaminophenylsulphonylglycine was lower in the cornea but similar in the conjunctiva. In both tissues, the permeability coefficient of 2-nitrobenzoylaminophenylsulphonylglycine was less than that of 4-nitrobenzoylaminophenylsulphonylglycine. There was no significant difference between the permeability coefficients of 3-nitro

  6. Connective tissue growth factor differentially binds to members of the cystine knot superfamily and potentiates platelet-derived growth factor-B signaling in rabbit corneal fibroblast cells

    PubMed Central

    Pi, Liya; Chung, Pei-Yu; Sriram, Sriniwas; Rahman, Masmudur M; Song, Wen-Yuan; Scott, Edward W; Petersen, Bryon E; Schultz, Gregory S

    2015-01-01

    AIM: To study the binding of connective tissue growth factor (CTGF) to cystine knot-containing ligands and how this impacts platelet-derived growth factor (PDGF)-B signaling. METHODS: The binding strengths of CTGF to cystine knot-containing growth factors including vascular endothelial growth factor (VEGF)-A, PDGF-B, bone morphogenetic protein (BMP)-4, and transforming growth factor (TGF)-β1 were compared using the LexA-based yeast two-hybrid system. EYG48 reporter strain that carried a wild-type LEU2 gene under the control of LexA operators and a lacZ reporter plasmid (p80p-lacZ) containing eight high affinity LexA binding sites were used in the yeast two-hybrid analysis. Interactions between CTGF and the tested growth factors were evaluated based on growth of transformed yeast cells on selective media and colorimetric detection in a liquid β-galactosidase activity assay. Dissociation constants of CTGF to VEGF-A isoform 165 or PDGF-BB homo-dimer were measured in surface plasma resonance (SPR) analysis. CTGF regulation in PDGF-B presentation to the PDGF receptor β (PDGFRβ) was also quantitatively assessed by the SPR analysis. Combinational effects of CTGF protein and PDGF-BB on activation of PDGFRβ and downstream signaling molecules ERK1/2 and AKT were assessed in rabbit corneal fibroblast cells by Western analysis. RESULTS: In the LexA-based yeast two-hybrid system, cystine knot motifs of tested growth factors were fused to the activation domain of the transcriptional factor GAL4 while CTGF was fused to the DNA binding domain of the bacterial repressor protein LexA. Yeast co-transformants containing corresponding fusion proteins for CTGF and all four tested cystine knot motifs survived on selective medium containing galactose and raffinose but lacking histidine, tryptophan, and uracil. In liquid β-galactosidase assays, CTGF expressing cells that were co-transformed with the cystine knot of VEGF-A had the highest activity, at 29.88 ± 0.91 fold above controls

  7. 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

  8. [Transplantation of corneal endothelial cells].

    PubMed

    Amano, Shiro

    2002-12-01

    culture of HCECs was possible using adult human serum. We reconstructed the cornea using cultured HCECs and human corneal stroma. The corneal stroma, on which the cell suspension of HCECs was poured, was mildly centrifuged to enhance the HCECs attachment to the stroma. The cell density of HCECs on the reconstructed cornea reached 2,500 cells/mm2. The pump function of the reconstructed cornea was measured with an Ussing chamber. The potential difference in the reconstructed cornea and normal cornea was 0.30 mV and 0.40 mV, respectively; indicating that the pump function of the reconstructed cornea is 75% of that of the normal cornea. The reconstructed cornea was transplanted to a rabbit eye and stayed transparent for 6 months after the operation. Fluorescein labeled cultured HCECs remained on the graft 1 month after the transplantation, indicating that transplanted HCECs contributed to the transparency of the graft. The possibility of using artificial stroma or porcine corneal stroma as a carrier of cultured HCECs was investigated. The artificial stroma made of alkaline-treated collagen could not be sutured but showed good transparency, biocompatibility, and cell-attachability. Porcine corneal stroma, expressing little xeno-sugar antigen alpha-gal epitope, induced no super acute rejection but mild cellular rejection when transplanted in the cornea of animals possessing natural antibody to alpha-gal epitope. The cornea reconstructed with porcine corneal stroma and HCECs had an average cell density of 1721/mm2 and had approximately 60% of the pump function of a normal cornea. As new technologies in corneal transplantation, the application of self immature cells and the direct delivery of cultured HCECs into the anterior chamber were investigated. Part of rat mononuclear cells that were obtained from the bone marrow and injected into the rat anterior chamber transformed into corneal endothelium-like cells, suggesting that self immature cells can transform into corneal

  9. 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 ...

  10. Corneal transplant

    MedlinePlus

    ... clear outer lens on the front of the eye. A corneal transplant is surgery to replace the cornea with tissue ... years. Rejection can sometimes be controlled with steroid eye drops. Other ... are: Bleeding Cataracts Infection of the eye Glaucoma ( ...

  11. [Animal experiment studies on the problem of treating corneal lesions].

    PubMed

    Niedermeier, S

    1987-01-01

    From the clinical point of view an ointment containing retinol, thiamine hydrochloride and calcium pantothenate (Regepithel) seems to be of benefit in the treatment of various corneal diseases. The influence of Regepithel on healing time after superficial corneal injuries in rabbits is demonstrated on the basis of comparative histological findings. PMID:3573651

  12. Corneal Regeneration by Deep Anterior Lamellar Keratoplasty (DALK) Using Decellularized Corneal Matrix

    PubMed Central

    Hashimoto, Yoshihide; Funamoto, Seiichi; Sasaki, Shuji; Negishi, Jun; Honda, Takako; Hattori, Shinya; Nam, Kwangwoo; Kimura, Tsuyoshi; Mochizuki, Manabu; Kobayashi, Hisatoshi; Kishida, Akio

    2015-01-01

    The purpose of this study is to demonstrate the feasibility of DALK using a decellularized corneal matrix obtained by HHP methodology. Porcine corneas were hydrostatically pressurized at 980 MPa at 10°C for 10 minutes to destroy the cells, followed by washing with EGM-2 medium to remove the cell debris. The HHP-treated corneas were stained with H-E to assess the efficacy of decellularization. The decellularized corneal matrix of 300 μm thickness and 6.0 mm diameter was transplanted onto a 6.0 mm diameter keratectomy wound. The time course of regeneration on the decellularized corneal matrix was evaluated by haze grading score, fluorescein staining, and immunohistochemistry. H-E staining revealed that no cell nuclei were observed in the decellularized corneal matrix. The decellularized corneal matrices were opaque immediately after transplantation, but became completely transparent after 4 months. Fluorescein staining revealed that initial migration of epithelial cells over the grafts was slow, taking 3 months to completely cover the implant. Histological sections revealed that the implanted decellularized corneal matrix was completely integrated with the receptive rabbit cornea, and keratocytes infiltrated into the decellularized corneal matrix 6 months after transplantation. No inflammatory cells such as macrophages, or neovascularization, were observed during the implantation period. The decellularized corneal matrix improved corneal transparency, and remodelled the graft after being transplanted, demonstrating that the matrix obtained by HHP was a useful graft for corneal tissue regeneration. PMID:26161854

  13. Enhanced regeneration of corneal tissue via a bioengineered collagen construct implanted by a nondisruptive surgical technique.

    PubMed

    Koulikovska, Marina; Rafat, Mehrdad; Petrovski, Goran; Veréb, Zoltán; Akhtar, Saeed; Fagerholm, Per; Lagali, Neil

    2015-03-01

    Severe shortage of donor corneas for transplantation, particularly in developing countries, has prompted the advancement of bioengineered tissue alternatives. Bioengineered corneas that can withstand transplantation while maintaining transparency and compatibility with host cells, and that are additionally amenable to standardized low-cost mass production are sought. In this study, a bioengineered porcine construct (BPC) was developed to function as a biodegradable scaffold to promote corneal stromal regeneration by host cells. Using high-purity medical-grade type I collagen, high 18% collagen content and optimized EDC-NHS cross-linker ratio, BPCs were fabricated into hydrogel corneal implants with over 90% transparency and four-fold increase in strength and stiffness compared with previous versions. Remarkably, optical transparency was achieved despite the absence of collagen fibril organization at the nanoscale. In vitro testing indicated that BPC supported confluent human epithelial and stromal-derived mesenchymal stem cell populations. With a novel femtosecond laser-assisted corneal surgical model in rabbits, cell-free BPCs were implanted in vivo in the corneal stroma of 10 rabbits over an 8-week period. In vivo, transparency of implanted corneas was maintained throughout the postoperative period, while healing occurred rapidly without inflammation and without the use of postoperative steroids. BPC implants had a 100% retention rate at 8 weeks, when host stromal cells began to migrate into implants. Direct histochemical evidence of stromal tissue regeneration was observed by means of migrated host cells producing new collagen from within the implants. This study indicates that a cost-effective BPC extracellular matrix equivalent can incorporate cells passively to initiate regenerative healing of the corneal stroma, and is compatible with human stem or organ-specific cells for future therapeutic applications as a stromal replacement for treating blinding

  14. A Native-Like Corneal Construct Using Donor Corneal Stroma for Tissue Engineering

    PubMed Central

    Lin, Jing; Yoon, Kyung-Chul; Zhang, Lili; Su, Zhitao; Lu, Rong; Ma, Ping; De Paiva, Cintia S.; Pflugfelder, Stephen C.; Li, De-Quan

    2012-01-01

    Tissue engineering holds great promise for corneal transplantation to treat blinding diseases. This study was to explore the use of natural corneal stroma as an optimal substrate to construct a native like corneal equivalent. Human corneal epithelium was cultivated from donor limbal explants on corneal stromal discs prepared by FDA approved Horizon Epikeratome system. The morphology, phenotype, regenerative capacity and transplantation potential were evaluated by hematoxylin eosin and immunofluorescent staining, a wound healing model, and the xeno-transplantation of the corneal constructs to nude mice. An optically transparent and stratified epithelium was rapidly generated on donor corneal stromal substrate and displayed native-like morphology and structure. The cells were polygonal in the basal layer and became flattened in superficial layers. The epithelium displayed a phenotype similar to human corneal epithelium in vivo. The differentiation markers, keratin 3, involucrin and connexin 43, were expressed in full or superficial layers. Interestingly, certain basal cells were immunopositive to antibodies against limbal stem/progenitor cell markers ABCG2 and p63, which are usually negative in corneal epithelium in vivo. It suggests that this bioengineered corneal epithelium shared some characteristics of human limbal epithelium in vivo. This engineered epithelium was able to regenerate in 4 days following from a 4mm-diameter wound created by a filter paper soaked with 1 N NaOH. This corneal construct survived well after xeno-transplantation to the back of a nude mouse. The transplanted epithelium remained multilayer and became thicker with a phenotype similar to human corneal epithelium. Our findings demonstrate that natural corneal stroma is an optimal substrate for tissue bioengineering, and a native-like corneal construct has been created with epithelium containing limbal stem cells. This construct may have great potential for clinical use in corneal

  15. 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.

  16. Mechanisms of allograft rejection of corneal endothelium

    SciTech Connect

    Tagawa, Y.; Silverstein, A.M.; Prendergast, R.A.

    1982-07-01

    The local intraocular graft-vs.-host (GVH) reaction, involving the destruction of the corneal endothelial cells of the rabbit host by sensitized donor lymphoid cells, has been used to study the mechanism of corneal allograft rejection. Pretreatment of donor cells with a specific mouse monoclonal hybridoma anti-T cell antibody and complement suppresses the destructive reaction, suggesting that a cellular-immune mechanism is primarily involved. Pretreatment of donor cells with mitomycin-C completely abolishes the local GVH reaction, indicating that the effector lymphocytes must undergo mitosis within the eye before they can engage in target cell destruction. Finally, studies of the local GVH reaction in irradiated leukopenic recipients or in preinflamed rabbit eyes suggest that host leukocytes may contribute nonspecifically to enhance the destructive process. These studies show that the local ocular GVH reaction may provide a useful model for the study of the mechanisms involved in the rejection of corneal allografts.

  17. Cultured corneal epithelia for ocular surface disease.

    PubMed Central

    Schwab, I R

    1999-01-01

    PURPOSE: To evaluate the potential efficacy for autologous and allogeneic expanded corneal epithelial cell transplants derived from harvested limbal corneal epithelial stem cells cultured in vitro for the management of ocular surface disease. METHODS: Human Subjects. Of the 19 human subjects included, 18 (20 procedures) underwent in vitro cultured corneal epithelial cell transplants using various carriers for the epithelial cells to determine the most efficacious approach. Sixteen patients (18 procedures on 17 eyes) received autologous transplants, and 2 patients (1 procedure each) received allogeneic sibling grafts. The presumed corneal epithelial stem cells from 1 patient did not grow in vitro. The carriers for the expanded corneal epithelial cells included corneal stroma, type 1 collagen (Vitrogen), soft contact lenses, collagen shields, and amniotic membrane for the autologous grafts and only amniotic membrane for the allogeneic sibling grafts. Histologic confirmation was reviewed on selected donor grafts. Amniotic membrane as carrier. Further studies were made to determine whether amniotic membrane might be the best carrier for the expanding corneal epithelial cells. Seventeen different combinations of tryspinization, sonication, scraping, and washing were studied to find the simplest, most effective method for removing the amniotic epithelium while still preserving the histologic appearance of the basement membrane of the amnion. Presumed corneal epithelial stem cells were harvested and expanded in vitro and applied to the amniotic membrane to create a composite graft. Thus, the composite graft consisted of the amniotic membrane from which the original epithelium had been removed without significant histologic damage to the basement membrane, and the expanded corneal epithelial stem cells, which had been applied to and had successfully adhered to the denuded amniotic membrane. Animal model. Twelve rabbits had the ocular surface of 1 eye damaged in a standard

  18. Collagen-immobilized poly(vinyl alcohol) as an artificial cornea scaffold that supports a stratified corneal epithelium.

    PubMed

    Miyashita, Hideyuki; Shimmura, Shigeto; Kobayashi, Hisatoshi; Taguchi, Tetsushi; Asano-Kato, Naoko; Uchino, Yuichi; Kato, Masabumi; Shimazaki, Jun; Tanaka, Junzo; Tsubota, Kazuo

    2006-01-01

    The cornea is a transparent tissue of the eye, which is responsible for the refraction of incoming light. Both biological corneal equivalents and synthetic keratoprostheses have been developed to replace donor tissue as a means to restore vision. However, both designs have drawbacks in terms of stability and biocompatibility. Clinically available synthetic devices do not support an intact epithelium, which poses a risk of microbial infection or protrusion of the prosthesis. In the present study, type I collagen was immobilized onto poly(vinyl alcohol) (PVA-COL) as a possible artificial cornea scaffold that can sustain a functional corneal epithelium. Human and rabbit corneal epithelial cells were air-lift cultured with 3T3 feeder fibroblasts to form a stratified epithelial layer on PVA-COL. The epithelial sheet expressed keratin 3/12 differentiation markers, the tight junction protein occludin, and had characteristic microvilli structures on transmission electron microscopy. Functionally, the stratified epithelium contained normal glycogen levels, and an apical tight-junction network was observed to exclude the diffusion of horseradish peroxidase. Furthermore, the epithelium-PVA-COL composite was suturable in the rabbit cornea, suggesting the possibility of using PVA-COL as a biocompatible material for keratoprosthesis. PMID:16044431

  19. Riboflavin concentration in corneal stroma after intracameral injection

    PubMed Central

    Li, Na; Peng, Xiu-Jun; Fan, Zheng-Jun; Pang, Xu; Xia, Yu; Wu, Teng-Fei

    2015-01-01

    AIM To evaluate the enrichment of riboflavin in the corneal stroma after intracameral injection to research the barrier ability of the corneal endothelium to riboflavin in vivo. METHODS The right eyes of 30 New Zealand white rabbits were divided into three groups. Different concentrations riboflavin-balanced salt solutions (BSS) were injected into the anterior chamber (10 with 0.5%, 10 with 1%, and 10 with 2%). Eight corneal buttons of 8.5 mm in diameter from each group were dissected at 30min after injection and the riboflavin concentrations in the corneal stroma were determined using high-performance liquid chromatography (HPLC) after removing the epithelium and endothelium. The other two rabbits in every group were observed for 24h and sacrificed. As a comparison, the riboflavin concentrations from 16 corneal stromal samples were determined using HPLC after instillation of 0.1% riboflavin-BSS solution for 30min on the corneal surface (8 without epithelium and 8 with intact epithelium). RESULTS The mean riboflavin concentrations were 11.19, 18.97, 25.08, 20.18, and 1.13 µg/g for 0.5%, 1%, 2%, de-epithelialzed samples, and the transepithelial groups, respectively. The color change of the corneal stroma and the HPLC results showed that enrichment with riboflavin similar to classical de-epithelialized corneal collagen crosslinking (CXL) could be achieved by intracameral 1% riboflavin-BSS solution after 30min; the effect appeared to be continuous for at least 30min. CONCLUSION Riboflavin can effectively penetrate the corneal stroma through the endothelium after an intracameral injection in vivo, so it could be an enhancing method that could improve the corneal riboflavin concentration in transepithelial CXL. PMID:26085993

  20. Corneal proteoglycan changes under vitamin A deficiency

    SciTech Connect

    Twining, S.S.; Wilson, P.M.

    1986-05-01

    The vitamin A-deficient keratinized cornea is very susceptible to ulceration possibly due to altered stromal components. In this study the proteoglycans present in the corneal stroma of vitamin A-deficient, pair-fed and normal rabbits were compared. Rabbits after weaning were placed on a vitamin A deficient diet, the same diet with retinyl palmitate added (pair-fed) or normal rabbit chow. After 5 months, the corneas of the vitamin A-deficient animals became keratinized. The corneal components were then labeled by injection of /sup 3/H-leucine and Na/sup 35/SO/sub 4/ into the anterior chamber of the eyes on 3 successive days. On the 4th day the animals were sacrificed the corneas removed and dissected. The labeled corneal stromas were extracted with 4 M GuHCl and the components separated on a DEAE-Sepharose column. The proteoglycans were eluted with 0.5 M and 1.0 M NaCl. The 1.0 M NaCl fraction (mainly keratin sulfate proteoglycans) was increased 25% in the vitamin A-deficient corneas over that for the pair-fed and normal corneas. These proteoglycans from the deficient corneas gave a different elution pattern on Octyl-Sepharose eluted with a Triton X-100 gradient than those from the pair-fed corneas. The total labeled proteoglycans were similar in the stromas from the 3 types of rabbits. These results indicate the various corneal proteoglycan ratios differ under vitamin A deficiency conditions.

  1. Corneal Abrasions and Corneal Foreign Bodies.

    PubMed

    Ahmed, Faheem; House, Robert James; Feldman, Brad Hal

    2015-09-01

    Corneal abrasions and corneal foreign bodies are frequently encountered ophthalmological injuries that are commonly diagnosed and managed by primary care physicians. The clinical course of a corneal epithelial defect can range from a relatively benign self-healing abrasion to a potentially sight-threatening complication such as a corneal ulcer, recurrent erosion, or traumatic iritis. A detailed clinical history regarding risk factors and exposure, along with a thorough slit lamp examination with fluorescein dye are essential for proper diagnosis and treatment, as well as to rule out penetrating globe injuries. Referral to an ophthalmologist is recommended in difficult cases or if other injuries are suspected. PMID:26319343

  2. Corneal Foreign Body

    MedlinePlus

    ... Care Guidelines As with corneal abrasions and recurrent erosion of the cornea, self-care includes: Never rubbing ... can be found about corneal abrasions and recurrent erosion of the cornea in their respective diagnoses. When ...

  3. Novel Therapy to Treat Corneal Epithelial Defects: A Hypothesis with Growth Hormone.

    PubMed

    Wirostko, Barbara; Rafii, MaryJane; Sullivan, David A; Morelli, Julia; Ding, Juan

    2015-07-01

    Impaired corneal wound healing that occurs with ocular surface disease, trauma, systemic disease, or surgical intervention can lead to persistent corneal epithelial defects (PCED), which result in corneal scarring, ulceration, opacification, corneal neovascularization, and, ultimately, visual compromise and vision loss. The current standard of care can include lubricants, ointments, bandage lenses, amniotic membranes, autologous serum eye drops, and corneal transplants. Various inherent problems exist with application and administration of these treatments, which often may not result in a completely healed surface. A topically applicable compound capable of promoting corneal epithelial cell proliferation and/or migration would be ideal to accelerate healing. We hypothesize that human growth hormone (HGH) is such a compound. In a recent study, HGH was shown to activate signal transducer and activators of transcription-5 (STAT5) signaling and promote corneal wound healing by enhancing corneal epithelial migration in a co-culture system of corneal epithelial cells and fibroblasts. These effects require an intact communication between corneal epithelia and fibroblasts. Further, HGH promotes corneal wound healing in a rabbit debridement model, thus demonstrating the effectiveness of HGH in vivo as well. In conclusion, HGH may represent an exciting and effective topical therapeutic to promote corneal wound healing. PMID:26045234

  4. Effects of topical travoprost 0.004% on intraocular pressure and corneal biomechanical properties in an animal model

    PubMed Central

    Lazcano-Gomez, Gabriel; Ancona-Lezama, David; Gil-Carrasco, Felix; Jimenez-Roman, Jesus

    2016-01-01

    Purpose To determine whether topical application of travoprost 0.004% induces changes in corneal biomechanical properties affecting intraocular pressure (IOP) values in rabbits. Methods Both eyes of 10 New Zealand rabbits were measured 3 times with the Ocular Response Analyzer (ORA) before treatment. Each measurement included corneal hysteresis (CH), corneal resistance factor (CRF), corneal-corrected IOP (IOPcc), and Goldmann equivalent IOP (IOPg). A drop of travoprost 0.004% was applied once daily in right eyes for 3 months; left eyes received no treatments. After 3 months of treatment both eyes of all rabbits were again measured 3 times. After complete keratectomy of both eyes, tissues prepared with hematoxylin-eosin stain were analyzed by means of light microscopy. Results The mean pre- and post-treatment IOPg, respectively, for right eyes was 9.92 ± 5.64 mm Hg and 7.62 ± 2.99 mm Hg (P = 0.027); IOPcc, 19.81 ± 5.25 mm Hg and 17.79 ± 4.09 mm Hg (P = 0.063); CRF, 1.65 ± 1.63 mm Hg and 2.18 ± 2.50 mm Hg (P = 0.266); and CH, 2.79 ± 1.74 mm Hg and 2.64 ± 2.08 mm Hg (P = 0.72). Mean post-treatment right and left eye IOPg values were, respectively, 7.62 ± 2.99 and 10.30 ± 4.40 (P = 0.002); IOPcc, 17.79 ± 4.09 mm Hg and 20.37 ± 4.32 mm Hg (P = 0.009); CRF, 1.65 ± 1.63 mm Hg and 2.17 ± 2.47 mm Hg (P = 0.274); and CH, 2.79 ± 1.74 mm Hg and 2.54 ± 2.08 mm Hg (P = 0.575). No difference in CH and CRF was observed between treated and untreated eyes. Conclusions Post-treatment reduction of IOP in treated eyes was a direct hypotensive effect of travoprost 0.004% and was not affected by changes in corneal biomechanical properties (CH and CRF), resulting in real lower IOP values. PMID:27330476

  5. Influence of borneol on in vitro corneal permeability and on in vivo and in vitro corneal toxicity.

    PubMed

    Yang, H; Xun, Y; Li, Z; Hang, T; Zhang, X; Cui, H

    2009-01-01

    This study examined whether borneol could enhance corneal drug permeability. Model drugs containing either synthetic or natural borneol were co-administered to isolated intact or de-epithelialized rabbit corneas and the apparent permeability coefficients were measured. Draize tests in rabbits and levels of isolated intact rabbit corneal hydration were used to measure in vivo and in vitro toxicity, respectively. Synthetic borneol (0.1%) increased corneal penetration of the lipophilic agents, indomethacin and dexamethasone, by 1.23 and 2.40, respectively, and of the hydrophilic agents, ofloxacin, ribavirin and tobramycin, by 1.87, 2.80 and 3.89, respectively. For natural borneol, the corresponding fold increases were 1.67, 2.00, 2.15, 2.18 and 3.39, respectively. Removing the epithelium attenuated the penetration-enhancing effects of borneol. Borneol (0.1%) did not damage corneal tissue. The ability of borneol to enhance drug penetration through the outer corneal layer, particularly for highly-hydrophilic drugs, suggests that further clinical investigation may be warranted. PMID:19589262

  6. 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.

  7. 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.

  8. Comparison of corneal sensitivity, tear function and corneal staining following laser in situ keratomileusis with two femtosecond laser platforms

    PubMed Central

    Petznick, Andrea; Chew, Annabel; Hall, Reece C; Chan, Cordelia ML; Rosman, Mohamad; Tan, Donald; Tong, Louis; Mehta, Jodhbir S

    2013-01-01

    Purpose To evaluate longitudinal changes in corneal sensitivity, tear function, and corneal staining in patients who underwent laser in situ keratomileusis (LASIK) using two different femtosecond lasers. Methods In a prospective, randomized clinical trial, contralateral eyes of 45 patients underwent flap creation by either VisuMax or IntraLase™ femtosecond laser. Corneal sensitivity, tear break up time (TBUT), Schirmer’s test, and corneal fluorescein staining were assessed preoperatively and at 1 week, 1 month, and 3 months postoperatively. Results There were no statistical differences in any clinical outcome measure between the two femtosecond lasers (P > 0.05), although there was a trend towards slightly lower reductions for corneal sensitivity and TBUT in VisuMax-operated eyes. Overall, corneal sensitivity was significantly reduced at 1 week (P < 0.05), 1 month (P < 0 .001), and 3 months (P < 0.001) postoperatively. A significantly greater reduction of corneal sensitivity was noted in eyes with a myopic spherical equivalent of −6.00 diopters (D) to −11.25 D as compared with eyes that had a relatively lower level of myopia of less than −6.00 D (P < 0.001). TBUT and Schirmer’s test values were significantly diminished at 1 week postoperatively (P < 0.04). Overall, corneal staining was significantly increased at 1 week postoperatively (P < 0.001). The level of myopia did not significantly affect postoperative changes in TBUT, Schirmer’s test values, or corneal staining (P > 0.05). Conclusion This study showed that changes in corneal sensitivity, tear function, and corneal staining were statistically similar in LASIK using VisuMax and IntraLase femtosecond lasers for flap creation. However, the trend towards faster recovery of corneal sensitivity and TBUT observed in VisuMax-operated eyes may be attributable to improved technical specifications. PMID:23576858

  9. Photothrombosis of Corneal Neovascularization by Photodynamic Therapy Utilizing Verteporfin and Diode Laser

    PubMed Central

    Ahmed Hassan, Aziza; Foad Ghoneim, Dina; Abdelraheem El-dib, Amr; Abdelkawi Ahmed, Salwa; Abdel- Salam, Ahmed Medhat

    2013-01-01

    Introduction: The aim of the present study was to evaluate the effect of photodynamic therapy in the treatment of experimental corneal neovascularization (NV) with benzoporphyrin derivative (BPD). Methods: One group was considered as control (n=6 eyes) then, corneal NV was induced in 30 New Zealand male rabbits (n=60 eyes) by placing 7.0 silk sutures at midstromal depth approximately1mm from the limbus. Fifteen rabbits with corneal NV were left without any treatment, and 15 rabbits were subjected to photodynamic therapy (PDT) by intravenous injection with Verteporfin at a dose of 1.5 mg /Kg. Diode laser (660 nm) was applied after 15 minutes for 5 minutes with a power of 50 mW/cm2. All rabbits were successively followed up by slit lamp examination for periods of 1 day, 1, 2, 3 and 4 weeks. Three rabbits were selected and sacrificed weekly (n=6 eyes each) and the corneas were isolated for histopathological examination. Results: The results of slit lamp examination indicated the gradual regression of the cornea neovascularization 4 weeks of PDT. Furthermore, regression of corneal neovascularization was documented clinically by decrease number and length of blood vessels and by histopathological examination. Conclusion: PDT with Verteporfin can provide efficacious treatment of corneal neovascularization. PMID:25606321

  10. Corneal cells for regeneration.

    PubMed

    Kinoshita, S; Nakamura, T

    2005-01-01

    In cases of corneal epithelial stem cell deficiency where ocular surface reconstruction is required, corneal epithelial replacement using a tissue engineering technique shows great potential. Autologous cultivated corneal epithelial stem cell sheets are the safest and most reliable forms of sheet we can use for such treatment; however, they are not useful for treating bilaterally affected ocular surface disorders. In order to treat such cases, we must choose either an allogeneic cultivated corneal epithelial sheet or an autologous cultivated oral mucosal epithelial sheet. If we use the former, the threat of immunological reaction must be dealt with. Therefore, it is imperative that we have a basic understanding of the immunological aspects of ocular surface reconstruction using allogeneic tissues. When using an autologous cultivated oral mucosal epithelial sheet, a basic understanding of ocular surface epithelial biology is required as the sheet is not exactly the same as corneal epithelium. PMID:16080287

  11. 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.

  12. Corneal toxicity induced by vesicating agents and effective treatment options.

    PubMed

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

    2016-06-01

    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 cells and rabbit corneal organ culture models with the SM analog nitrogen mustard, 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

  13. Corneal blindness and xenotransplantation.

    PubMed

    Lamm, Vladimir; Hara, Hidetaka; Mammen, Alex; Dhaliwal, Deepinder; Cooper, David K C

    2014-01-01

    Approximately 39 million people are blind worldwide, with an estimated 285 million visually impaired. The developing world shoulders 90% of the world's blindness, with 80% of causative diseases being preventable or treatable. Blindness has a major detrimental impact on the patient, community, and healthcare spending. Corneal diseases are significant causes of blindness, affecting at least 4 million people worldwide. The prevalence of corneal disease varies between parts of the world. Trachoma, for instance, is the second leading cause of blindness in Africa, after cataracts, but is rarely found today in developed nations. When preventive strategies have failed, corneal transplantation is the most effective treatment for advanced corneal disease. The major surgical techniques for corneal transplantation include penetrating keratoplasty (PK), anterior lamellar keratoplasty, and endothelial keratoplasty (EK). Indications for corneal transplantation vary between countries, with Fuchs' dystrophy being the leading indication in the USA and keratoconus in Australia. With the exception of the USA, where EK will soon overtake PK as the most common surgical procedure, PK is the overwhelming procedure of choice. Success using corneal grafts in developing nations, such as Nepal, demonstrates the feasibility of corneal transplantation on a global scale. The number of suitable corneas from deceased human donors that becomes available will never be sufficient, and so research into various alternatives, for example stem cells, amniotic membrane transplantation, synthetic and biosynthetic corneas, and xenotransplantation, is progressing. While each of these has potential, we suggest that xenotransplantation holds the greatest potential for a corneal replacement. With the increasing availability of genetically engineered pigs, pig corneas may alleviate the global shortage of corneas in the near future. PMID:25268248

  14. Donor corneal tissue evaluation.

    PubMed

    Saini, J S; Reddy, M K; Sharma, S; Wagh, S

    1996-03-01

    Proper evaluation of donor cornea is critical to the success of corneal transplantation. Attention must be paid to the cause of death and ocular condition as several general and ocular diseases constitute contraindications for donor corneal usage. Death to enucleation time should be noted. Gross examination and slit lamp biomicroscopy are mandatory for the evaluation of the donor eye while specular microscopy adds another useful dimension to information regarding donor cornea. This article provides a comprehensive review of all the aspects of donor corneal evaluation as practised today worldwide. PMID:8828299

  15. Infrared laser welding of the rabbit cornea in vivo

    NASA Astrophysics Data System (ADS)

    Williams, John M.; Burstein, Neal L.; Nowicki, Michael J.; Zietkiewicz, Christopher J.; Jeffers, William Q.

    1995-05-01

    The hydrogen fluoride laser has been used to successfully weld corneal tissue in vivo. Previous experiments have demonstrate the success of producing watertight welds in both porcine and human cadaver corneas. Wound bursting strengths of up to three times normal intraocular pressure have been reported. In this study, an in vivo model was utilized, specifically the rabbit cornea. Twelve New Zealand white rabbits, received a 7 mm, full thickness, linear corneal incision in one eye, and stay sutures were placed. Six of the wounds were welded with a semiconductor infrared laser, and six eyes served as controls. At two and four weeks, both histologic and tensiometric studies were performed. There was a trend toward increasing wound strength when the two and four week specimens were compared. Corneal welding may prove to be an adjunct to current suturing techniques in humans. Procedures requiring the closure of corneal incisions such as cataract extraction or penetrating keratoplasty may benefit from this technique.

  16. Adipose-derived mesenchymal stem cell administration does not improve corneal graft survival outcome.

    PubMed

    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

  17. 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

  18. Corneal cross-linking.

    PubMed

    Randleman, J Bradley; Khandelwal, Sumitra S; Hafezi, Farhad

    2015-01-01

    Since its inception in the late 1990s, corneal cross-linking has grown from an interesting concept to a primary treatment for corneal ectatic disease worldwide. Using a combination of ultraviolet-A light and a chromophore (vitamin B2, riboflavin), the cornea can be stiffened, usually with a single application, and progressive thinning diseases such as keratoconus arrested. Despite being in clinical use for many years, some of the underlying processes, such as the role of oxygen and the optimal treatment times, are still being worked out. More than a treatment technique, corneal cross-links represent a physiological principle of connective tissue, which may explain the enormous versatility of the method. We highlight the history of corneal cross-linking, the scientific underpinnings of current techniques, evolving clinical treatment parameters, and the use of cross-linking in combination with refractive surgery and for the treatment of infectious keratitis. PMID:25980780

  19. Importance of Corneal Thickness

    MedlinePlus

    ... News About Us Donate In This Section The Importance of Corneal Thickness email Send this article to ... is important because it can mask an accurate reading of eye pressure, causing doctors to treat you ...

  20. Refractive corneal surgery - discharge

    MedlinePlus

    Nearsightedness surgery - discharge; Refractive surgery - discharge; LASIK - discharge; PRK - discharge ... You had refractive corneal surgery to help improve your vision. This surgery uses a laser to reshape your cornea. It corrects ...

  1. Delayed Corneal Epithelial Healing after Intravitreal Bevacizumab: A Clinical and Experimental Study

    PubMed Central

    Colombres, Gustavo A; Gramajo, Ana L; Arrambide, Maria P; Juarez, Silvina M; Arevalo, J Fernando; Bar, Jorge; Juarez, Claudio P; Luna, Jose D

    2011-01-01

    Purpose To report corneal epithelial defects (CEDs) and delayed epithelial healing after intravitreal bevacizumab (IVB) injection and to describe delayed corneal epithelial healing with topical administration of bevacizumab in an experimental rabbit model. Methods A retrospective chart review was performed on 850 eyes of 850 patients with neovascular eye disease and diabetic macular edema who had received 1.25 to 2.5 mg IVB. In the experimental arm of the study, photorefractive keratectomy was used to create a 3 mm CED in the right eyes of 18 New Zealand rabbits which were then randomized to three equal groups. All rabbits received topical antibiotics, additionally those in group A received topical bevacizumab and animals in group B were treated with topical corticosteroids. The rate of epithelial healing was assessed at different time points using slitlamp photography. Results In the clinical study, seven eyes of seven subjects developed CEDs the day after IVB injection. All of these eyes had preexisting corneal edema. The healing period ranged from 3 to 38 days (average 11 days) despite appropriate medical management. In the experimental study, topical bevacizumab and corticosteroids both significantly hindered corneal epithelial healing at 12 and 24 hours. Conclusion Bevacizumab was demonstrated to cause CEDs in clinical settings. Moreover, corneal epithelial healing was delayed by topical application of bevacizumab, in the experimental model. These short-term results suggest that corneal edema may be considered as a risk factor for epithelial defects after IVB. PMID:22454702

  2. Effects of diabetic keratopathy on corneal optical density, central corneal thickness, and corneal endothelial cell counts

    PubMed Central

    Gao, Feng; Lin, Tao; Pan, Yingzhe

    2016-01-01

    Diabetic keratopathy is an ocular complication that occurs with diabetes. In the present study, the effect of diabetic keratopathy on corneal optical density, central corneal thickness, and corneal endothelial cell count was investigated. One hundred and eighty diabetic patients (360 eyes) were enrolled in the study during the period from March, 2012 to March, 2013. The patients were divided into three age groups: <5, 5–10 and >10 years, with 60 patients per group (120 eyes). During the same period, 60 healthy cases (120 eyes) were selected and labeled as the normal control group. The Pentacam was used to measure the corneal optical density, and central corneal thickness. Specular microscopy was used to examine the corneal endothelial cell density. The coefficient of partial correlation was used to control age and correlate the analysis between the corneal optical density, corneal endothelial cell density, and central corneal thickness. The stage of the disease, the medial and intimal corneal optical density and central corneal thickness was analyzed in the diabetes group. The corneal optical density in the diabetes group increased compared with that of the normal control group. The medial and intimal corneal optical density and central corneal thickness were positively correlated with the course of the disease. However, the corneal endothelial cell density was not associated with the course of diabetes. There was a positive association between the medial and intimal corneal optical density and central corneal thickness of the diabetic patients. In conclusion, the results of the present study show that medial and intimal corneal optical density and central corneal thickness were sensitive indicators for early diabetic keratopathy.

  3. The Favorable Effect of Mesenchymal Stem Cell Treatment on the Antioxidant Protective Mechanism in the Corneal Epithelium and Renewal of Corneal Optical Properties Changed after Alkali Burns.

    PubMed

    Cejka, Cestmir; Holan, Vladimir; Trosan, Peter; Zajicova, Alena; Javorkova, Eliska; Cejkova, Jitka

    2016-01-01

    The aim of this study was to examine whether mesenchymal stem cells (MSCs) and/or corneal limbal epithelial stem cells (LSCs) influence restoration of an antioxidant protective mechanism in the corneal epithelium and renewal of corneal optical properties changed after alkali burns. The injured rabbit corneas (with 0.25 N NaOH) were untreated or treated with nanofiber scaffolds free of stem cells, with nanofiber scaffolds seeded with bone marrow MSCs (BM-MSCs), with adipose tissue MSCs (Ad-MSCs), or with LSCs. On day 15 following the injury, after BM-MSCs or LSCs nanofiber treatment (less after Ad-MSCs treatment) the expression of antioxidant enzymes was restored in the regenerated corneal epithelium and the expressions of matrix metalloproteinase 9 (MMP9), inducible nitric oxide synthase (iNOS), α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and vascular endothelial factor (VEGF) were low. The central corneal thickness (taken as an index of corneal hydration) increased after the injury and returned to levels before the injury. In injured untreated corneas the epithelium was absent and numerous cells revealed the expressions of iNOS, MMP9, α-SMA, TGF-β1, and VEGF. In conclusion, stem cell treatment accelerated regeneration of the corneal epithelium, restored the antioxidant protective mechanism, and renewed corneal optical properties. PMID:27057279

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

    PubMed Central

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

    2015-01-01

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

  5. Disposal rabbit

    DOEpatents

    Lewis, L.C.; Trammell, D.R.

    1983-10-12

    A disposable rabbit for transferring radioactive samples in a pneumatic transfer system comprises aerated plastic shaped in such a manner as to hold a radioactive sample and aerated such that dissolution of the rabbit in a solvent followed by evaporation of the solid yields solid waste material having a volume significantly smaller than the original volume of the rabbit.

  6. Disposable rabbit

    DOEpatents

    Lewis, Leroy C.; Trammell, David R.

    1986-01-01

    A disposable rabbit for transferring radioactive samples in a pneumatic transfer system comprises aerated plastic shaped in such a manner as to hold a radioactive sample and aerated such that dissolution of the rabbit in a solvent followed by evaporation of the solid yields solid waste material having a volume significantly smaller than the original volume of the rabbit.

  7. Hydrogen prevents corneal endothelial damage in phacoemulsification cataract surgery.

    PubMed

    Igarashi, Tsutomu; Ohsawa, Ikuroh; Kobayashi, Maika; Igarashi, Toru; Suzuki, Hisaharu; Iketani, Masumi; Takahashi, Hiroshi

    2016-01-01

    In phacoemulsification, ultrasound induces hydroxyl radical (·OH) formation, damaging corneal endothelium. Whether H2 can prevent such oxidative damage in phacoemulsification was examined by in vitro and in vivo studies. H2 was dissolved in a commercial irrigating solution. The effects of H2 against ·OH generation were first confirmed in vitro by electron-spin resonance (ESR) and hydroxyphenyl fluorescein (HPF). ESR showed a significantly decreased signal magnitude, and fluorescence intensity by oxidized HPF was significantly less in the H2-dissolved solution. The effects of H2 in phacoemulsification were evaluated in rabbits, comparing H2-dissolved and control solutions. Five hours after the procedure, the whole cornea was excised and subjected to image analysis for corneal edema, real-time semiquantitative PCR (qPCR) for heme oxygenase (HO)-1, catalase (CAT), superoxide dismutase 1 (SOD1), and SOD2 mRNA, and immunohistochemistry. Corneal edema was significantly less and the increases in anti-oxidative HO-1, CAT and SOD2 mRNA expressions were significantly suppressed in the H2 group. In addition, corneal endothelial cell expressions of two oxidative stress markers, 4-HNE and 8-OHdG, were significantly lower in the H2 group. In conclusion, H2 dissolved in the ocular irrigating solution protected corneal endothelial cells from phacoemulsification-induced oxidative stress and damage. PMID:27498755

  8. Hydrogen prevents corneal endothelial damage in phacoemulsification cataract surgery

    PubMed Central

    Igarashi, Tsutomu; Ohsawa, Ikuroh; Kobayashi, Maika; Igarashi, Toru; Suzuki, Hisaharu; Iketani, Masumi; Takahashi, Hiroshi

    2016-01-01

    In phacoemulsification, ultrasound induces hydroxyl radical (·OH) formation, damaging corneal endothelium. Whether H2 can prevent such oxidative damage in phacoemulsification was examined by in vitro and in vivo studies. H2 was dissolved in a commercial irrigating solution. The effects of H2 against ·OH generation were first confirmed in vitro by electron-spin resonance (ESR) and hydroxyphenyl fluorescein (HPF). ESR showed a significantly decreased signal magnitude, and fluorescence intensity by oxidized HPF was significantly less in the H2-dissolved solution. The effects of H2 in phacoemulsification were evaluated in rabbits, comparing H2-dissolved and control solutions. Five hours after the procedure, the whole cornea was excised and subjected to image analysis for corneal edema, real-time semiquantitative PCR (qPCR) for heme oxygenase (HO)-1, catalase (CAT), superoxide dismutase 1 (SOD1), and SOD2 mRNA, and immunohistochemistry. Corneal edema was significantly less and the increases in anti-oxidative HO-1, CAT and SOD2 mRNA expressions were significantly suppressed in the H2 group. In addition, corneal endothelial cell expressions of two oxidative stress markers, 4-HNE and 8-OHdG, were significantly lower in the H2 group. In conclusion, H2 dissolved in the ocular irrigating solution protected corneal endothelial cells from phacoemulsification-induced oxidative stress and damage. PMID:27498755

  9. Clinical aspects of corneal trachoma.

    PubMed Central

    Hosni, F A

    1978-01-01

    Classification of trachoma by site rather than density of opacities is better related to visual prognosis and helps in selection for graft surgery. The cases are divided into 3 groups: peripheral corneal opacities, central corneal opacities, and diffuse corneal opacities (ground-glass cornea). A central lesion has the poorest prognosis, especially in children. PMID:638107

  10. Long-term outcomes of wedge resection at the limbus for high irregular corneal astigmatism after repaired corneal laceration

    PubMed Central

    Du, Jun; Zheng, Guang-Ying; Wen, Cheng-Lin; Zhang, Xiao-Fang; Zhu, Yu

    2016-01-01

    AIM To evaluate the clinical value of wedge resection at corneal limbus in patients with traumatic corneal scarring and high irregular astigmatism. METHODS Patients with traumatic corneal astigmatism received wedge resection at least 6mo after suture removal from corneal wound. The uncorrected distance visual acuities (UCVA) and best corrected distance visual acuities (BCVA), pre- and post-operation astigmatism, spherical equivalent (SE), safety and complications were evaluated. RESULTS Ten eyes (10 patients) were enrolled in this study. Mean follow-up time after wedge resection was 37.8±15.4mo (range, 20-61mo). The mean UCVA improved from +1.07±0.55 logMAR to +0.43±0.22 logMAR (P=0.000) and the mean BCVA from +0.50±0.30 logMAR to +0.15±0.17 logMAR (P=0.000). The mean astigmatism power measured by retinoscopy was -2.03±2.27 D postoperatively and -2.83±4.52 D preoperatively (P=0.310). The mean SE was -0.74±1.61 D postoperatively and -0.64±1.89 D preoperatively (P=0.601). Two cases developed mild pannus near the sutures. No corneal perforation, infectious keratitis or wound gape occurred. CONCLUSION Corneal-scleral limbal wedge resection with compression suture is a safe, effective treatment for poor patients with high irregular corneal astigmatism after corneal-scleral penetrating injury. Retinoscopy can prove particularly useful for high irregular corneal astigmatism when other measurements are not amenable. PMID:27366685

  11. 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.

  12. Rabbit models for continuous curvilinear capsulorhexis instruction

    PubMed Central

    Ruggiero, Jason; Keller, Christopher; Porco, Travis; Naseri, Ayman; Sretavan, David W.

    2012-01-01

    PURPOSE To develop a rabbit model for continuous curvilinear capsulorhexis (CCC) instruction. SETTING University of California San Francisco, San Francisco, California, USA. DESIGN Experimental study. METHODS Isolated rabbit lenses were immersed in 2% to 8% paraformaldehyde (PFA) fixative from 15 minutes to 6 hours. Rabbit eyes were treated by substituting aqueous with 2% to 4% PFA for 30 minutes to 6 hours, followed by washes with a balanced salt solution. Treated lenses and eyes were held in purpose-designed holders using vacuum. A panel of 6 cataract surgeons with 5 to 15 years of experience performed CCC on treated lenses and eyes and responded to a questionnaire regarding the utility of these models for resident teaching using a 5-item Likert scale. RESULTS The expert panel found that rabbit lenses treated with increasing amounts of fixative simulated CCC on human lens capsules from the third to the seventh decade of life. The panel also found fixative-treated rabbit eyes to simulate some of the experience of CCC within the human anterior chamber but noted a shallower anterior chamber depth, variation in pupil size, and corneal clouding under some treatment conditions. CONCLUSIONS Experienced cataract surgeons who performed CCC on these rabbit models strongly agreed that isolated rabbit lenses treated with fixative provide a realistic simulation of CCC in human patients and that both models were useful tools for capsulorhexis instruction. Results indicate that rabbit lenses treated with 8% PFA for 15 minutes is a model with good fidelity for CCC training. PMID:22727296

  13. Advances in corneal preservation.

    PubMed Central

    Lindstrom, R L

    1990-01-01

    The functional status of the endothelium and sustained corneal deturgescence after corneal preservation are of great clinical importance and have been primary goals in the development of corneal storage media. In our investigational studies we have specifically addressed the improvement of the quality of donor tissue after 4 degrees C storage, the extension of corneal preservation time, the enhancement of corneal wound healing, and the reduction of the normal progressive loss of endothelial cells postkeratoplasty. Specifically we have developed in vitro HCE cell and epithelial cell culture models that can accurately reflect the response of human corneal tissue in vivo. These models have been utilized to study the effects of growth factors and medium components in relation to their biocompatibility and efficacy in the development of improved corneal preservation solutions. Our laboratory investigated in vitro conditions that allowed human corneal endothelium to shift from a nonproliferative state, in which they remain viable and metabolically active, to a proliferative, mitotically active state. Isolation techniques developed in our laboratory have enabled the establishment of primary and subsequent subcultures of human corneal endothelium that retain the attributes of native endothelium. These in vitro conditions maintain HCE cells in a proliferative state, actively undergoing mitosis. A quantitative bioassay has been developed to determine the effects of various test medium in the stimulation or inhibition of DNA synthesis. In attempting to learn more about the events that occur during in vitro endothelial cell isolation, cell reattachment, extracellular matrix interaction and migrating during subculture, SEM was done on isolated HCE cells incubated in CSM. These studies suggest that the components of the extracellular matrix modulate the growth response of HCE cells, and play a role in regulating proliferation and migration. These observations are important in

  14. Immune Privilege of Corneal Allografts

    PubMed Central

    Niederkorn, Jerry Y.; Larkin, D. Frank P.

    2013-01-01

    Corneal transplantation has been performed successfully for over 100 years. Normally, HLA typing and systemic immunosuppressive drugs are not utilized, yet 90% of corneal allografts survive. In rodents, corneal allografts representing maximal histoincompatibility enjoy >50% survival even without immunosuppressive drugs. By contrast, other categories of transplants are invariably rejected in such donor/host combinations. The acceptance of corneal allografts compared to other categories of allografts is called immune privilege. The cornea expresses factors that contribute to immune privilege by preventing the induction and expression of immune responses to histocompatibility antigens on the corneal allograft. Among these are soluble and cell membrane molecules that block immune effector elements and also apoptosis of T lymphocytes. However, some conditions rob the corneal allograft of its immune privilege and promote rejection, which remains the leading cause of corneal allograft failure. Recent studies have examined new strategies for restoring immune privilege to such high-risk hosts. PMID:20482389

  15. 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

  16. 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

  17. Modeling of Corneal and Retinal Pharmacokinetics after Periocular Drug Administration

    PubMed Central

    Amrite, Aniruddha C.; Edelhauser, Henry F.; Kompella, Uday B.

    2012-01-01

    Purpose To develop pharmacokinetics models to describe the disposition of small lipophilic molecules in the cornea and retina after periocular (subconjunctival or posterior subconjunctival) administration. Methods Compartmental pharmacokinetics analysis was performed on the corneal and retinal data obtained after periocular administration of 3 mg of celecoxib (a selective COX-2 inhibitor) to Brown Norway (BN) rats. Berkeley Madonna, a differential and difference equation–based modeling software, was used for the pharmacokinetics modeling. The data were fit to different compartment models with first-order input and disposition, and the best fit was selected on the basis of coefficient of regression and Akaike information criteria (AIC). The models were validated by using the celecoxib data from a prior study in Sprague-Dawley (SD) rats. The corneal model was also fit to the corneal data for prednisolone at a dose of 2.61 mg in albino rabbits, and the model was validated at two other doses of prednisolone (0.261 and 26.1 mg) in these rabbits. Model simulations were performed with the finalized model to understand the effect of formulation on corneal and retinal pharmacokinetics after periocular administration. Results Celecoxib kinetics in the BN rat cornea can be described by a two-compartment (periocular space and cornea, with a dissolution step for periocular formulation) model, with parallel elimination from the cornea and the periocular space. The inclusion of a distribution compartment or a dissolution step for celecoxib suspension did not lead to an overall improvement in the corneal data fit compared with the two-compartment model. The more important parameter for enhanced fit and explaining the apparent lack of an increase phase in the corneal levels is the inclusion of the initial leak-back of the dose from the periocular space into the precorneal area. The predicted celecoxib concentrations from this model also showed very good correlation (r = 0

  18. The phacoemulsification procedure. II. Corneal endothelial changes.

    PubMed

    Polack, F M; Sugar, A

    1976-06-01

    The effect of phacoemulsification, with the Cavitron-Kelman instrument, on the corneal endothelium of rabbit and cats was studied by scanning electron microscopy and nitroblue tetrazolium staining. The various steps of the procedure were examined separately. Irrigation of the anterior chamber of the eye with balanced salt solution (Plasma-Lyte) for ten minutes caused no cell damage. Ultrasound and irrigation alone for four to six minutes caused increased permeability to NBT. Edema of endothelial cells and cell junction disruption occurred after eight minutes of anterior chamber irrigation with Plasma-Lyte. Uncomplicated phacoemulsification produced moderate cellular edema with scattered loss of endothelial cells. Destruction of endothelial cells was frequent after phacoemulsification, it appeared to be due to lens nucleus manipulation in the anterior chamber, instrumentation, and needle contact. From two to five days postoperatively, intercellular edema, altered cell morphology, and mosaic pattern were seen. However, it gradually recovered and seven to ten days later the endothelium appeared normal. PMID:931690

  19. Noncontact depth-resolved micro-scale corneal elastography

    NASA Astrophysics Data System (ADS)

    Wang, Shang; Larin, Kirill V.

    2015-03-01

    Noninvasive high-resolution depth-resolved measurement of corneal biomechanics is of great clinical significance for improving the diagnosis and optimizing the treatment of various degenerated ocular diseases. Here, we report a micro-scale optical coherence elastography (OCE) method that enables noncontact assessment of the depthwise elasticity distribution in the cornea. The OCE system combines a focused air-puff device with phase-sensitive optical coherence tomography (OCT). Low-pressure short-duration air stream is used to load the cornea with the localized displacement at micron level. The phase-resolved OCT detection with nano-scale sensitivity probes the induced corneal deformation at various locations within a scanning line, providing the ultra-fast imaging of the corneal lamb wave propagation. With spectral analysis, the amplitude spectra and the phase spectra are available for the estimation of the frequency range of the lamb wave and the quantification of the wave propagation, respectively. Curved propagation paths following the top and bottom corneal boundaries are selected inside the cornea for measuring the phase velocity of the lamb wave at the major frequency components over the whole depths. Our pilot experiments on ex vivo rabbit eyes indicate the distinct stiffness of different layers in the cornea, including the epithelium, the anterior stroma, the posterior stroma, and the innermost region, which demonstrates the feasibility of this micro-scale OCE method for noncontact depth-resolved corneal elastography. Also, the quantification of the lamb wave dispersion in the cornea could lead to the measurement of the elastic modulus, suggesting the potential of this method for quantitative monitoring of the corneal biomechanics.

  20. WNT7A and PAX6 define corneal epithelium homeostasis and pathogenesis.

    PubMed

    Ouyang, Hong; Xue, Yuanchao; Lin, Ying; Zhang, Xiaohui; Xi, Lei; Patel, Sherrina; Cai, Huimin; Luo, Jing; Zhang, Meixia; Zhang, Ming; Yang, Yang; Li, Gen; Li, Hairi; Jiang, Wei; Yeh, Emily; Lin, Jonathan; Pei, Michelle; Zhu, Jin; Cao, Guiqun; Zhang, Liangfang; Yu, Benjamin; Chen, Shaochen; Fu, Xiang-Dong; Liu, Yizhi; Zhang, Kang

    2014-07-17

    The surface of the cornea consists of a unique type of non-keratinized epithelial cells arranged in an orderly fashion, and this is essential for vision by maintaining transparency for light transmission. Cornea epithelial cells (CECs) undergo continuous renewal from limbal stem or progenitor cells (LSCs), and deficiency in LSCs or corneal epithelium--which turns cornea into a non-transparent, keratinized skin-like epithelium--causes corneal surface disease that leads to blindness in millions of people worldwide. How LSCs are maintained and differentiated into corneal epithelium in healthy individuals and which key molecular events are defective in patients have been largely unknown. Here we report establishment of an in vitro feeder-cell-free LSC expansion and three-dimensional corneal differentiation protocol in which we found that the transcription factors p63 (tumour protein 63) and PAX6 (paired box protein PAX6) act together to specify LSCs, and WNT7A controls corneal epithelium differentiation through PAX6. Loss of WNT7A or PAX6 induces LSCs into skin-like epithelium, a critical defect tightly linked to common human corneal diseases. Notably, transduction of PAX6 in skin epithelial stem cells is sufficient to convert them to LSC-like cells, and upon transplantation onto eyes in a rabbit corneal injury model, these reprogrammed cells are able to replenish CECs and repair damaged corneal surface. These findings suggest a central role of the WNT7A-PAX6 axis in corneal epithelial cell fate determination, and point to a new strategy for treating corneal surface diseases. PMID:25030175

  1. Transparent, resilient human amniotic membrane laminates for corneal transplantation.

    PubMed

    Hariya, Takehiro; Tanaka, Yuji; Yokokura, Shunji; Nakazawa, Toru

    2016-09-01

    This study evaluated a new technique to toughen and optically clarify human amniotic membrane (AM) tissue, which is naturally thin and clouded, and determined the suitability of the altered tissue for corneal transplantation. The technique created a tissue laminate by repeatedly depositing wet layers of AM and dehydrating them, followed by chemical cross-linking to tighten integration at the layer interfaces and within the layers, thereby improving the physical properties of the laminates by increasing light transmittance and mechanical strength. Interestingly, this improvement only occurred in laminates with at least 4 layers. Cross-linking also improved the resistance of the laminates to collagenase degradation, such as occurs in corneal melting. This study also confirmed that the AM tissue was biocompatible by inserting AM monolayers into the corneal stroma of rabbits, and by performing lamellar keratoplasty in rabbits with cross-linked AM laminates. The laminates were sufficiently thick and resilient to need only one set of sutures, whereas in previously described multi-layer AM transplantation technique, each layer required separate sutures. The current findings are a promising advance in the engineering of novel biomaterials and the alteration of existing tissues for medical use. PMID:27267629

  2. Nanomedicine Approaches for Corneal Diseases

    PubMed Central

    Chaurasia, Shyam S.; Lim, Rayne R.; Lakshminarayanan, Rajamani; Mohan, Rajiv R.

    2015-01-01

    Corneal diseases are the third leading cause of blindness globally. Topical nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, antibiotics and tissue transplantation are currently used to treat corneal pathological conditions. However, barrier properties of the ocular surface necessitate high concentration of the drugs applied in the eye repeatedly. This often results in poor efficacy and several side-effects. Nanoparticle-based molecular medicine seeks to overcome these limitations by enhancing the permeability and pharmacological properties of the drugs. The promise of nanomedicine approaches for treating corneal defects and restoring vision without side effects in preclinical animal studies has been demonstrated. Numerous polymeric, metallic and hybrid nanoparticles capable of transporting genes into desired corneal cells to intercept pathologic pathways and processes leading to blindness have been identified. This review provides an overview of corneal diseases, nanovector properties and their applications in drug-delivery and corneal disease management. PMID:25941990

  3. Corneal thickness in glaucoma.

    PubMed

    De Cevallos, E; Dohlman, C H; Reinhart, W J

    1976-02-01

    The central corneal stromal thickness of patients with open angle glaucoma, secondary glaucoma (the majority aphakic), or a history of unilateral acute angle closure glaucoma were measured and compared with the stromal thickness of a group of normal patients. In open angle glaucoma, there was a small but significant increase in the average stromal thickness. This thickness increase was, in all likelihood, due to an abnormal function of the endothelium in this disease since the level of the intraocular pressure did not seem to be a factor. There was no correlation between stromal thickness and duration of the glaucoma or type of anti-glaucomatous medication. Most cases of secondary glaucome, controlled medically or not, had markedly increased corneal thickness, again, most likely, due to endothelial damage rather than to level of intraocular pressure. After an angle closure attack, permanent damage to the cornea was found to be rare. PMID:1247273

  4. Fuchs’ corneal dystrophy

    PubMed Central

    Eghrari, Allen O; Gottsch, John D

    2010-01-01

    Fuchs’ corneal dystrophy (FCD) is a progressive, hereditary disease of the cornea first described a century ago by the Austrian ophthalmologist Ernst Fuchs. Patients often present in the fifth to sixth decade of life with blurry morning vision that increases in duration as the disease progresses. Primarily a condition of the posterior cornea, characteristic features include the formation of focal excrescences of Descemet membrane termed ‘guttae’, loss of endothelial cell density and end-stage disease manifested by corneal edema and the formation of epithelial bullae. Recent advances in our understanding of the genetic and pathophysiological mechanisms of the disease, as well as the application of new imaging modalities and less invasive surgical procedures, present new opportunities for improved outcomes among patients with FCD. PMID:20625449

  5. Generation and Feasibility Assessment of a New Vehicle for Cell-Based Therapy for Treating Corneal Endothelial Dysfunction

    PubMed Central

    Okumura, Naoki; Kakutani, Kazuya; Inoue, Ryota; Matsumoto, Daiki; Shimada, Tomoki; Nakahara, Makiko; Kiyanagi, Yumiko; Itoh, Takehiro; Koizumi, Noriko

    2016-01-01

    The corneal endothelium maintains corneal transparency by its pump and barrier functions; consequently, its decompensation due to any pathological reason causes severe vision loss due to corneal haziness. Corneal transplantation is the only therapeutic choice for treating corneal endothelial dysfunction, but associated problems, such as a shortages of donor corneas, the difficulty of the surgical procedure, and graft failure, still need to be resolved. Regenerative medicine is attractive to researchers as a means of providing innovative therapies for corneal endothelial dysfunction, as it now does for other diseases. We previously demonstrated the successful regeneration of corneal endothelium in animal models by injecting cultured corneal endothelial cells (CECs) in combination with a Rho kinase (ROCK) inhibitor. The purpose of the present study was to optimize the vehicle for clinical use in cell-based therapy. Our screening of cell culture media revealed that RELAR medium promoted CEC adhesion. We then modified RELAR medium by removing hormones, growth factors, and potentially toxic materials to generate a cell therapy vehicle (CTV) composed of amino acid, salts, glucose, and vitamins. Injection of CECs in CTV enabled efficient engraftment and regeneration of the corneal endothelium in the rabbit corneal endothelial dysfunction model, with restoration of a transparent cornea. The CECs retained >85% viability after a 24 hour preservation as a cell suspension in CTV at 4°C and maintained their potency to regenerate the corneal endothelium in vivo. The vehicle developed here is clinically applicable for cell-based therapy aimed at treating the corneal endothelium. Our strategy involves the generation of vehicle from a culture medium appropriate for a given cell type by removing materials that are not favorable for clinical use. PMID:27355373

  6. Generation and Feasibility Assessment of a New Vehicle for Cell-Based Therapy for Treating Corneal Endothelial Dysfunction.

    PubMed

    Okumura, Naoki; Kakutani, Kazuya; Inoue, Ryota; Matsumoto, Daiki; Shimada, Tomoki; Nakahara, Makiko; Kiyanagi, Yumiko; Itoh, Takehiro; Koizumi, Noriko

    2016-01-01

    The corneal endothelium maintains corneal transparency by its pump and barrier functions; consequently, its decompensation due to any pathological reason causes severe vision loss due to corneal haziness. Corneal transplantation is the only therapeutic choice for treating corneal endothelial dysfunction, but associated problems, such as a shortages of donor corneas, the difficulty of the surgical procedure, and graft failure, still need to be resolved. Regenerative medicine is attractive to researchers as a means of providing innovative therapies for corneal endothelial dysfunction, as it now does for other diseases. We previously demonstrated the successful regeneration of corneal endothelium in animal models by injecting cultured corneal endothelial cells (CECs) in combination with a Rho kinase (ROCK) inhibitor. The purpose of the present study was to optimize the vehicle for clinical use in cell-based therapy. Our screening of cell culture media revealed that RELAR medium promoted CEC adhesion. We then modified RELAR medium by removing hormones, growth factors, and potentially toxic materials to generate a cell therapy vehicle (CTV) composed of amino acid, salts, glucose, and vitamins. Injection of CECs in CTV enabled efficient engraftment and regeneration of the corneal endothelium in the rabbit corneal endothelial dysfunction model, with restoration of a transparent cornea. The CECs retained >85% viability after a 24 hour preservation as a cell suspension in CTV at 4°C and maintained their potency to regenerate the corneal endothelium in vivo. The vehicle developed here is clinically applicable for cell-based therapy aimed at treating the corneal endothelium. Our strategy involves the generation of vehicle from a culture medium appropriate for a given cell type by removing materials that are not favorable for clinical use. PMID:27355373

  7. Non-mulberry Silk Fibroin Biomaterial for Corneal Regeneration

    PubMed Central

    Hazra, Sarbani; Nandi, Sudip; Naskar, Deboki; Guha, Rajdeep; Chowdhury, Sushovan; Pradhan, Nirparaj; Kundu, Subhas C.; Konar, Aditya

    2016-01-01

    Purpose: Successful repair of a damaged corneal surface is a great challenge and may require the use of a scaffold that supports cell growth and differentiation. Amniotic membrane is currently used for this purpose, in spite of its limitations. A thin transparent silk fibroin film from non-mulberry Antheraea mylitta (Am) has been developed which offers to be a promising alternative. The silk scaffolds provide sufficient rigidity for easy handling, the scaffolds support the sprouting, migration, attachment and growth of epithelial cells and keratocytes from rat corneal explants; the cells form a cell sheet, preserve their phenotypes, express cytokeratin3 and vimentin respectively. The films also support growth of limbal stem cell evidenced by expression of ABCG2. The cell growth on the silk film and the amniotic membrane is comparable. The implanted film within the rabbit cornea remains transparent, stable. The clinical examination as well as histology shows absence of any inflammatory response or neovascularization. The corneal surface integrity is maintained; tear formation, intraocular pressure and electroretinography of implanted eyes show no adverse changes. The silk fibroin film from non-mulberry silk worms may be a worthy candidate for use as a corneal scaffold. PMID:26908015

  8. Biocompatibility of poly(ethylene glycol) and poly(acrylic acid) interpenetrating network hydrogel by intrastromal implantation in rabbit cornea.

    PubMed

    Zheng, Luo Luo; Vanchinathan, Vijay; Dalal, Roopa; Noolandi, Jaan; Waters, Dale J; Hartmann, Laura; Cochran, Jennifer R; Frank, Curtis W; Yu, Charles Q; Ta, Christopher N

    2015-10-01

    We evaluated the biocompatibility of a poly(ethylene glycol) and poly(acrylic acid) (PEG/PAA) interpenetrating network hydrogel designed for artificial cornea in a rabbit model. PEG/PAA hydrogel measuring 6 mm in diameter was implanted in the corneal stroma of twelve rabbits. Stromal flaps were created with a microkeratome. Randomly, six rabbits were assigned to bear the implant for 2 months, two rabbits for 6 months, two rabbits for 9 months, one rabbit for 12 months, and one rabbit for 16 months. Rabbits were evaluated monthly. After the assigned period, eyes were enucleated, and corneas were processed for histology and immunohistochemistry. There were clear corneas in three of six rabbits that had implantation of hydrogel for 2 months. In the six rabbits with implant for 6 months or longer, the corneas remained clear in four. There was a high rate of epithelial defect and corneal thinning in these six rabbits. One planned 9-month rabbit developed extrusion of implant at 4 months. The cornea remained clear in the 16-month rabbit but histology revealed epithelial in-growth. Intrastromal implantation of PEG/PAA resulted in a high rate of long-term complications. PMID:25778285

  9. CD147 Required for Corneal Endothelial Lactate Transport

    PubMed Central

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

    2014-01-01

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

  10. Corneal Cross-Linking (with a Partial Deepithelization) in Keratoconus with Five Years of Follow-Up

    PubMed Central

    Galvis, Virgilio; Tello, Alejandro; Carreño, Néstor I.; Ortiz, Alvaro I.; Barrera, Rodrigo; Rodriguez, Carlos Julián; Ochoa, Miguel E.

    2016-01-01

    We performed a retrospective interventional case series including 80 eyes of 48 patients with keratoconus (KC) who were treated with modified corneal cross-linking (CXL) for KC (with a partial deepithelization in a pattern of stripes). The average follow-up was 5.8 years (with a minimum of 5 years). At the last follow-up visit, compared with preoperative values, there were no significant changes in spherical equivalent, average keratometry, corneal thickness, corneal hysteresis, or corneal resistance factor. The distance-corrected visual acuity was 20/39 preoperatively and 20/36 postoperatively (P = 0.3). The endothelial cell count decreased by 4.7% (P < 0.005). These findings suggest that this modified corneal CXL technique is a safe and effective alternative to halt the progression of KC up to five years after the procedure. However, some concerns remain as to whether this technique can affect in some degree the corneal endothelial cells. PMID:27199574

  11. Assessment of corneal hydration sensing in the terahertz band: in vivo results at 100 GHz

    NASA Astrophysics Data System (ADS)

    Bennett, David; Taylor, Zachary; Tewari, Pria; Sung, Sijun; Maccabi, Ashkan; Singh, Rahul; Culjat, Martin; Grundfest, Warren; Hubschman, Jean-Pierre; Brown, Elliott

    2012-09-01

    Terahertz corneal hydration sensing has shown promise in ophthalmology applications and was recently shown to be capable of detecting water concentration changes of about two parts in a thousand in ex vivo corneal tissues. This technology may be effective in patient monitoring during refractive surgery and for early diagnosis and treatment monitoring in diseases of the cornea. In this work, Fuchs dystrophy, cornea transplant rejection, and keratoconus are discussed, and a hydration sensitivity of about one part in a hundred is predicted to be needed to successfully distinguish between diseased and healthy tissues in these applications. Stratified models of corneal tissue reflectivity are developed and validated using ex vivo spectroscopy of harvested porcine corneas that are hydrated using polyethylene glycol solutions. Simulation of the cornea's depth-dependent hydration profile, from 0.01 to 100 THz, identifies a peak in intrinsic reflectivity contrast for sensing at 100 GHz. A 100 GHz hydration sensing system is evaluated alongside the current standard ultrasound pachymetry technique to measure corneal hydration in vivo in four rabbits. A hydration sensitivity, of three parts per thousand or better, was measured in all four rabbits under study. This work presents the first in vivo demonstration of remote corneal hydration sensing.

  12. Knockdown of NBCe1 In Vivo Compromises the Corneal Endothelial Pump

    PubMed Central

    Liu, Cailing; Cheng, Qiang; Nguyen, Tracy

    2010-01-01

    Purpose. To evaluate the role of the sodium bicarbonate cotransporter (NBCe1) as a component of the corneal endothelial pump in the in vivo rabbit eye. Methods. Lentiviruses with NBCe1 shRNA and GFP expression cassettes were injected intracamerally. Knockdown efficacy was determined 1 week to 4 weeks later by immunofluorescence, Western blot analysis, and PCR. Functional effects were monitored by corneal thickness (CT) and brinzolamide sensitivity. Results. Within 24 hours there was a modest anterior chamber inflammation that resolved within 48 hours. At 4 × 106 IFU, more than 95% of the corneal endothelial surface showed GFP fluorescence above background within 7 days. At 14 to 21 days, signs of anterior chamber inflammation reemerged, and endothelial cell GFP fluorescence disappeared within 40 days after injection. The second phase of inflammation could be avoided by using GFP-less viruses. There was no significant difference in CT between scrambled sequence and NBCe1 shRNA–injected eyes over 3 weeks. Two drops of 1% brinzolamide produced 7.85% ± 3.3% corneal swelling within 5 hours of topical instillation. However, in corneas showing more than 25% NBCe1 knockdown (30 of 42 rabbits; 59% ± 15% knockdown), corneal swelling was significantly higher (10.1% ± 2.9%) relative to control eyes. Conclusions. FIV-based lentiviral vectors can transfect CE with shRNA in rabbits. The response to GFP is consistent, with previous studies showing the production of anti-GFP antibodies. Partial knockdown of NBCe1 did not affect baseline CT, which is consistent with the corneal endothelium having a substantial functional reserve. Provocative testing using, brinzolamide, however, revealed an underlying deficiency, confirming the importance of NBCe1 bicarbonate transport and demonstrating the concerted action between NBCe1 and carbonic anhydrases. PMID:20445126

  13. Long-term evaluation of corneal endothelial cell transplantation.

    PubMed Central

    Mohay, J; Wood, T O; McLaughlin, B J

    1997-01-01

    PURPOSE: This report describes the clinical course, refractive changes, confocal microscopic and histological evaluation of corneal endothelial cell transplantation in rabbits with long-term follow-up. METHODS: Transplantation of corneal endothelial cells using a cell/carrier device was performed in 19 rabbits. Clinical evaluation between 1-25 months included slit-lamp examination, keratometry, retinoscopy and surface topography. Two grafts in rabbits with 12 and 24 month survivals were evaluated in vivo by 3D tandem scanning confocal microscopy. The same grafts were then processed for transmission electron microscopy. BrdU labeling of the grafted cells in one transplant was performed in order to distinguish between host and grafted endothelial cells. RESULTS: All grafts cleared and remained clear for an average of one year without signs of rejection or inflammation. Postoperative refraction data and topography of the transplants showed progressive development of myopia and steep corneas compared to the unoperated eyes in each case. Confocal microscopy in vivo demonstrated a regular hexagonal pattern of the transplanted endothelial cells and a thickened Descemet's membrane, which correlated with the light and electron microscopic findings. BrdU labeling of the grafted endothelial cells showed a homogenous labeling of cell nuclei 6 months after the transplantation. CONCLUSIONS: This study demonstrates that corneal endothelial cells grown on a biomaterial can be replaced and remain functional for a long period of time. Images FIGURE 1 FIGURE 2A FIGURE 2B FIGURE 2C FIGURE 3A FIGURE 3B FIGURE 4 FIGURE 5 FIGURE 6A FIGURE 6B FIGURE 7 FIGURE 8A FIGURE 8B FIGURE 8C FIGURE 8D FIGURE 8E FIGURE 8F FIGURE 9 PMID:9440167

  14. Advances in corneal cell therapy.

    PubMed

    Fuest, Matthias; Yam, Gary Hin-Fai; Peh, Gary Swee-Lim; Mehta, Jodhbir S

    2016-09-01

    Corneal integrity is essential for visual function. Transplantation remains the most common treatment option for advanced corneal diseases. A global donor material shortage requires a search for alternative treatments. Different stem cell populations have been induced to express corneal cell characteristics in vitro and in animal models. Yet before their application to humans, scientific and ethical issues need to be solved. The in vitro propagation and implantation of primary corneal cells has been rapidly evolving with clinical practices of limbal epithelium transplantation and a clinical trial for endothelial cells in progress, implying cultivated ocular cells as a promising option for the future. This review reports on the latest developments in primary ocular cell and stem cell research for corneal therapy. PMID:27498943

  15. Corneal amyloidosis associated with keratoconus.

    PubMed

    Stern, G A; Knapp, A; Hood, C I

    1988-01-01

    Nodular, gray-white, central corneal opacities which extended from the subepithelial zone through the anterior four fifths of the stroma developed in a 50-year-old man with a longstanding history of hard contact lens wear for keratoconus. Results of histopathologic analysis of the corneal button obtained at the time of penetrating keratoplasty disclosed that the opacities were composed of amyloid. Corneal amyloidosis is rarely found in association with keratoconus. Although there were some similarities in the pattern of amyloid deposition to that seen in primary familial amyloidosis of the cornea, the authors believe that their patient is more likely to have had a secondary amyloidosis. Corneal amyloidosis should be considered in keratoconus patients with development of unusual forms of central corneal opacification. PMID:3278260

  16. Corneal Biomechanical Properties in Myopic Eyes Measured by a Dynamic Scheimpflug Analyzer

    PubMed Central

    Wang, Jingyi; Li, Ying; Jin, Yumei; Yang, Xue; Zhao, Chan; Long, Qin

    2015-01-01

    Purpose. To evaluate the corneal biomechanical parameters in myopic and emmetropic eyes using Corneal Visualization Scheimpflug Technology (CorVis ST). Methods. 103 myopic and emmetropic eyes of 103 patients were examined. Corneal biomechanical parameters, axial length, and mean keratometry were measured using CorVis ST, IOL Master, and topography, respectively. Corneal biomechanical properties were compared within four groups. Bivariate correlation analysis was used to assess the relationship between corneal biomechanical parameters and ocular characteristics. Results. Four of ten corneal biomechanical parameters, namely, deformation amplitude (DA), first- and second-applanation time (A1-time, A2-time), and radius at highest concavity (HC radius), were significantly different within the four groups (P < 0.05). In correlation analysis, DA was positively correlated with axial length (r = 0.20, P = 0.04); A2-time was positively correlated with spherical equivalent (SE) (r = 0.24, P = 0.02); HC radius was positively correlated with SE (r = 0.24, P = 0.02) and was negatively correlated with mean keratometry (r = −0.20, P = 0.046) and axial length (r = −0.21, P = 0.03). Conclusions. The corneal refraction-related biomechanical alterations were associated with ocular characteristics. Highly myopic eyes exhibited longer DA and smaller HC radius than do moderately myopic eyes; the eyes with longer axial length tend to have less corneal stiffness and are easier to deform under stress. PMID:26576291

  17. Corneal seal device

    NASA Technical Reports Server (NTRS)

    Baehr, E. F. (Inventor)

    1977-01-01

    A corneal seal device is provided which, when placed in an incision in the eye, permits the insertion of a surgical tool or instrument through the device into the eye. The device includes a seal chamber which opens into a tube which is adapted to be sutured to the eye and serves as an entry passage for a tool. A sealable aperture in the chamber permits passage of the tool through the chamber into the tube and hence into the eye. The chamber includes inlet ports adapted to be connected to a regulated source of irrigation fluid which provides a safe intraocular pressure.

  18. Spatial characterization of corneal biomechanical properties with optical coherence elastography after UV cross-linking.

    PubMed

    Twa, Michael D; Li, Jiasong; Vantipalli, Srilatha; Singh, Manmohan; Aglyamov, Salavat; Emelianov, Stanislav; Larin, Kirill V

    2014-05-01

    Corneal collagen cross-linking (CXL) is a clinical treatment for keratoconus that structurally reinforces degenerating ocular tissue, thereby limiting disease progression. Clinical outcomes would benefit from noninvasive methods to assess tissue material properties in affected individuals. Regional variations in tissue properties were quantified before and after CXL in rabbit eyes using optical coherence elastography (OCE) imaging. Low-amplitude (<1µm) elastic waves were generated using micro air-pulse stimulation and the resulting wave amplitude and speed were measured using phase-stabilized swept-source OCE. OCE imaging following CXL treatment demonstrates increased corneal stiffness through faster elastic wave propagation speeds and lower wave amplitudes. PMID:24877005

  19. [Neurotrophic keratopathy--studies on substance P and the clinical significance of corneal sensation].

    PubMed

    Nishida, T; Nakamura, M; Konma, T; Ofuji, K; Nagano, K; Tanaka, T; Enoki, M; Reid, T W; Brown, S M; Murphy, C J; Mannis, M J

    1997-12-01

    Neurotrophic keratopathy, which often follows damage to the trigeminal nerve, is clinically characterized by various types of epithelial disorders and melting of corneal stroma. To understand both the pathology of neurotrophic keratopathy and the physiological significance of corneal sensation, we investigated both the cellular and molecular functions of a sensory neurotransmitter, substance P, in corneal epithelial cells. Our findings prompted us to try a new mode of treatment for neurotrophic keratopathy. Substance P, a member of the tachykinin family, is an 11-amino-acid peptide. In an organ culture system using rabbit corneas, substance P alone had no effect on corneal epithelial migration. In the presence of insulin-like growth factor-1 (IGF-1), however, substance P synergistically facilitated corneal epithelial migration in proportion to the concentration of substance P or of IGF-1. Other neurotransmitters (acetylcholine, norepinephrine, serotonin etc.) or tachykinins (neurokinin A, eledoisin etc.) did not show this synergistic effect with IGF-1. Among receptors for the tachykinin family (NK-1, NK-2, or NK-3) only the NK-1 receptor system was involved in the synergistic effect of substance P and IGF-1 on corneal epithelial migration. IGF-1 affected neither the binding constant nor the number of sites of substance P receptors in corneal epithelial cells, suggesting that the synergistic effect was not regulated at the receptor level. Various extracellular signals activate the intracellular signal transduction system, thus amplifying specific biological functions. We found that the addition of inhibitors of protein kinase C or tyrosine kinase clearly inhibited the synergistic effect of substance P and IGF-1 on corneal epithelial migration, demonstrating that protein kinase C and tyrosine kinase are involved in the synergistic effect. During corneal epithelial wound healing, epithelial cells must attach to a provisional, extracellular fibronectin matrix. We

  20. Topical fluconazole for experimental candida keratitis in rabbits.

    PubMed Central

    Behrens-Baumann, W; Klinge, B; Rüchel, R

    1990-01-01

    Using a reproducible model of Candida albicans keratitis in rabbits we studied the effect of topical fluconazole, a new triazole. Candida albicans DSM 70010 (2.5 X 10(5) cells) was injected into the corneal stroma of both eyes of 21 rabbits. All eyes developed a corneal ulcer. Forty-eight hours after inoculation the animals were divided into three groups: (1) 14 eyes, received fluconazole (2 mg/ml) and the epithelium subsequently removed; (2) 14 eyes, received only fluconazole drops; (3) 14 eyes, received 0.9% NaCl: half of this group was also debrided. We applied one drop of either substance 10 times a day for 24 days. A further six rabbits were used to judge if the drug penetrated into the cornea and aqueous humour. There was a highly significant difference between the fluconazole groups (1,2) and the control group (3) as to hypopyon and complications (descemetocele, corneal perforation) as well as recultivation of C. albicans from corneal tissue. The difference between the fluconazole groups with and without debridement was not significant. The drug penetrated into the cornea and aqueous humour of both uninflamed and inflamed eyes. Images PMID:2306443

  1. Experimental study on the mechanical strain of corneal collagen.

    PubMed

    Avetisov, S E; Bubnova, I A; Novikov, I A; Antonov, A A; Siplivyi, V I

    2013-06-21

    Currently, investigations of biomechanical properties of the fibrous tunic are becoming even more topical, especially for diagnosis of corneal ectatic disease, as well as correct interpretation of intraocular pressure (IOP) parameters, particularly in patients with prior surgery on cornea. The study principle is based on the ability of substances to change optical anisotropy depending on mechanical strain applied to them. An experimental set-up was constructed which allows assessment of polarization degree of light which is emitted during luminescence of strained collagen. The study was performed on 18 corneoscleral discs of chinchilla rabbit eyes at 15 and 50mm Hg pressure, among them in 6 cases before and after making radial incisions, and in 6 cases before and after conducting the mechanical cornea abrasions that were asymmetrical by depth until reaching the local zone of iatrogenic keratectasia. Corneal collagen mechanical strain mappings were formed on 3 experimental models (intact cornea, cornea post radial keratotomy and keratectasia) under intra-chamber pressure of 15 and 50mm Hg. Corneal collagen mechanical strain is evenly allocated in the intact cornea. After radial keratotomy the main mechanical loading was concentrated over the middle part of corneal periphery, particularly in the bottom of keratotomic incisions. The increased intra-chamber pressure made the strain rise in those models. Upon cornea abrasion the main straining is distributed within the thinning zone, and the increase of intra-chamber pressure only increases the load over residual stroma. A new principle of corneal biomechanical properties investigation based on assessment of degree of light polarization emitted during luminescence of strained collagen, has been proposed and experimentally tested. PMID:23680349

  2. Intrastromal Delivery of Bevacizumab Using Microneedles to Treat Corneal Neovascularization

    PubMed Central

    Kim, Yoo C.; Grossniklaus, Hans E.; Edelhauser, Henry F.; Prausnitz, Mark R.

    2014-01-01

    Purpose. This study tested the hypothesis that highly targeted intrastromal delivery of bevacizumab using coated microneedles allows dramatic dose sparing compared with subconjunctival and topical delivery for treatment of corneal neovascularization. Methods. Stainless steel microneedles 400 μm in length were coated with bevacizumab. A silk suture was placed in the cornea approximately 1 mm from the limbus to induce corneal neovascularization in the eyes of New Zealand white rabbits that were divided into different groups: untreated, microneedle delivery, topical eye drop, and subconjunctival injection of bevacizumab. All drug treatments were initiated 4 days after suture placement and area of neovascularization was measured daily by digital photography for 18 days. Results. Eyes treated once with 4.4 μg bevacizumab using microneedles reduced neovascularization compared with untreated eyes by 44% (day 18). Eyes treated once with 2500 μg bevacizumab using subconjunctival injection gave similar results to microneedle-treated eyes. Eyes treated once with 4.4 μg subconjunctival bevacizumab showed no significant effect compared with untreated eyes. Eyes treated with 52,500 μg bevacizumab by eye drops three times per day for 14 days reduced the neovascularization area compared with untreated eyes by 6% (day 18), which was significantly less effective than the single microneedle treatment. Visual exam and histological analysis showed no observable effect of microneedle treatment on corneal transparency or microanatomical structure. Conclusions. This study shows that microneedles can target drug delivery to corneal stroma in a minimally invasive way and demonstrates effective suppression of corneal neovascularization after suture-induced injury using a much lower dose compared with conventional methods. PMID:25212779

  3. Corneal structure and transparency

    PubMed Central

    Meek, Keith M.; Knupp, Carlo

    2015-01-01

    The corneal stroma plays several pivotal roles within the eye. Optically, it is the main refracting lens and thus has to combine almost perfect transmission of visible light with precise shape, in order to focus incoming light. Furthermore, mechanically it has to be extremely tough to protect the inner contents of the eye. These functions are governed by its structure at all hierarchical levels. The basic principles of corneal structure and transparency have been known for some time, but in recent years X-ray scattering and other methods have revealed that the details of this structure are far more complex than previously thought and that the intricacy of the arrangement of the collagenous lamellae provides the shape and the mechanical properties of the tissue. At the molecular level, modern technologies and theoretical modelling have started to explain exactly how the collagen fibrils are arranged within the stromal lamellae and how proteoglycans maintain this ultrastructure. In this review we describe the current state of knowledge about the three-dimensional stromal architecture at the microscopic level, and about the control mechanisms at the nanoscopic level that lead to optical transparency. PMID:26145225

  4. 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

  5. Excimer laser phototherapeutic keratectomy in eyes with anterior corneal dystrophies: preoperative and postoperative ultrasound biomicroscopic examination and short-term clinical outcomes with and without an antihyperopia treatment.

    PubMed Central

    Rapuano, Christopher J

    2003-01-01

    PURPOSE: To evaluate the use of high-frequency ultrasound biomicroscopy (UBM) in determining the depth of corneal pathology in eyes undergoing excimer laser phototherapeutic keratectomy (PTK) for primary or recurrent anterior stromal corneal dystrophies. Corneal clarity, visual acuity and refractive changes in eyes with and without an antihyperopia treatment were also analyzed. METHODS: Twenty eyes of 14 patients with anterior stromal corneal dystrophies were treated with PTK. Eyes were evaluated preoperatively and 6 to 8 weeks postoperatively with slit-lamp biomicroscopy, manifest refraction, keratometry, computerized corneal topography, ultrasound pachymetry, and UBM. RESULTS: Nineteen of 20 corneas (95%) had greatly improved corneal clarity after PTK. Mean uncorrected Snellen vision improved from 20/102 to 20/69 and best corrected vision improved from 20/62 to 20/38. Nine eyes (45%) improved 2 or more lines of uncorrected vision, and 13 eyes (65%) improved 2 or more lines of best corrected vision. Mean change in spherical equivalent was just -0.92 diopters (D); however, the range was large (-13 to +3.88 D). UBM measurement of central corneal pathology did not correlate with the actual PTK ablation depth (P = .07). The amount of antihyperopia treatment did not correlate with changes in manifest refraction spherical equivalent, keratometry, or computerized corneal topography readings, but did correlate with length of time until corneal reepithelialization after PTK (P = .003). CONCLUSIONS: PTK resulted in improvements in corneal clarity and visual acuity in most patients with superficial corneal stromal dystrophies. UBM was not an effective tool to accurately measure the depth of corneal pathology preoperatively. The combined approach of minimizing ablation depth and selective use of an antihyperopia treatment resulted in minimal mean change in spherical equivalent; however, the range was large. PTK is a very good minimally invasive technique to improve vision in

  6. Silk Fibroin as a Biomaterial Substrate for Corneal Epithelial Cell Sheet Generation

    PubMed Central

    Liu, Jingbo; Lawrence, Brian D.; Liu, Aihong; Schwab, Ivan R.; Oliveira, Lauro A.; Rosenblatt, Mark I.

    2012-01-01

    Purpose. To evaluate a silk fibroin (SF) biomaterial as a substrate for corneal epithelial cell proliferation, differentiation, and stratification in vitro compared with denuded human amniotic membrane (AM). Methods. Primary human and rabbit corneal epithelial cells and immortalized human corneal limbal epithelial cells were cultured on the SF and denuded AM, respectively. The biological cell behavior, including the morphology, proliferation, differentiation, and stratification, on the two substrates was compared and analyzed. Results. Corneal epithelial cells can adhere and proliferate on the SF and denuded AM with a cobblestone appearance, abundant microvilli on the surface, and wide connection with the adjacent cells. MTT assay showed that cell proliferation on denuded AM was statistically higher than that on SF at 24 and 72 hours after plating (P = 0.001 and 0.0005, respectively). Expression of ΔNp63a and keratin 3/12 was detected in primary cell cultures on the two substrates with no statistical difference. When cultured at the air-liquid interface for 7 days, cells on SF could form a comparable stratified graft with a 2- to 3-cell layering, which compared similarly to AM cultures. Conclusions. SF, a novel biomaterial, could support corneal epithelial cells to proliferate, differentiate, and stratify, retaining the normal characteristic epithelium phenotype. Compared with AM, its unique features, including the transparency, ease of handling, and transfer, and inherent freedom from disease transmission, make it a promising substrate for corneal wound repair and tissue-engineering purposes. PMID:22661480

  7. 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

  8. 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

  9. Management of advanced corneal ectasias.

    PubMed

    Maharana, Prafulla K; Dubey, Aditi; Jhanji, Vishal; Sharma, Namrata; Das, Sujata; Vajpayee, Rasik B

    2016-01-01

    Corneal ectasias include a group of disorders characterised by progressive thinning, bulging and distortion of the cornea. Keratoconus is the most common disease in this group. Other manifestations include pellucid marginal degeneration, Terrien's marginal degeneration, keratoglobus and ectasias following surgery. Advanced ectasias usually present with loss of vision due to high irregular astigmatism. Management of these disorders is difficult due to the peripheral location of ectasia and associated severe corneal thinning. Newer contact lenses such as scleral lenses are helpful in a selected group of patients. A majority of these cases requires surgical intervention. This review provides an update on the current treatment modalities available for management of advanced corneal ectasias. PMID:26294106

  10. The corneal fibrosis response to epithelial-stromal injury.

    PubMed

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

    2016-01-01

    The corneal wound healing response, including the development of stromal opacity in some eyes, is a process that often leads to scarring that occurs after injury, surgery or infection to the cornea. Immediately after epithelial and stromal injury, a complex sequence of processes contributes to wound repair and regeneration of normal corneal structure and function. In some corneas, however, often depending on the type and extent of injury, the response may also lead to the development of mature vimentin+ α-smooth muscle actin+ desmin+ myofibroblasts. Myofibroblasts are specialized fibroblastic cells generated in the cornea from keratocyte-derived or bone marrow-derived precursor cells. The disorganized extracellular matrix components secreted by myofibroblasts, in addition to decreased expression of corneal crystallins in these cells, are central biological processes that result in corneal stromal fibrosis associated with opacity or "haze". Several factors are associated with myofibroblast generation and haze development after PRK surgery in rabbits, a reproducible model of scarring, including the amount of tissue ablated, which may relate to the extent of keratocyte apoptosis in the early response to injury, irregularity of stromal surface after surgery, and changes in corneal stromal proteoglycans, but normal regeneration of the epithelial basement membrane (EBM) appears to be a critical factor determining whether a cornea heals with relative transparency or vision-limiting stromal opacity. Structural and functional abnormalities of the regenerated EBM facilitate prolonged entry of epithelium-derived growth factors such as transforming growth factor β (TGF-β) and platelet-derived growth factor (PDGF) into the stroma that both drive development of mature myofibroblasts from precursor cells and lead to persistence of the cells in the anterior stroma. A major discovery that has contributed to our understanding of haze development is that keratocytes and corneal

  11. Corneal Transplantation and Immune Privilege

    PubMed Central

    Niederkorn, Jerry Y.

    2013-01-01

    Corneal transplants have been successfully performed in human subjects for over 100 years and enjoy an immune privilege that is unrivaled in the field of transplantation. Immune privilege is defined as the reduced incidence and tempo in the immune rejection of corneal allografts compared to other categories of organ allografts performed under the same conditions. Skin allografts transplanted across various MHC or minor histocompatibility barriers undergo rejection in approximately 100% of the hosts. By contrast, orthotopic corneal allografts experience long-term survival in 50% to >90% of the hosts, depending on the histocompatibility barriers that confront the host. The capacity of corneal allografts to evade immune rejection is attributable to multiple anatomical, physiological, and immunoregulatory conditions that conspire to prevent the induction and expression of alloimmunity. PMID:23360158

  12. Suppression of chemotaxis to corneal inflammation by nitrous oxide.

    PubMed

    Kripke, B J; Kupferman, A; Luu, K C

    1987-11-01

    Immune competency is depressed in the perioperative period. The role of anesthetic agents in immune reactivity remains unclear. The chemotactic migration of polymorphonuclear leukocytes (PMNs) to the cornea of rabbits injured by clove oil was studied. PMNs were previously radiolabeled with tritiated (3H) thymidine. Immediately following injury, the rabbits entered isolation chambers and breathed either air or air containing 10%, 20% or 40% nitrous oxide (N2O) for 24 hours. After sacrifice, the radioactivity of a 10 mm corneal button, removed by trephination, was determined by scintillation counting technique. Peripheral blood was obtained for hemoglobin, white cell and platelet count. The N2O dosage affected on the migration of PMNs to the cornea. 3H was decreased 15.4% by 20% N2O and 38.8% for 40% N2O-exposed rabbits. Peripheral blood values did not differ. N2O can suppress chemotaxis of PMNs in the rabbit, thereby adversely affecting the inflammatory component of immune defense. PMID:3130236

  13. Contributions of tissue-specific pathologies to corneal injuries following exposure to SM vapor.

    PubMed

    McNutt, Patrick M; Tuznik, Kaylie M; Glotfelty, Elliot J; Nelson, Marian R; Lyman, Megan E; Hamilton, Tracey A

    2016-06-01

    Corneal injuries resulting from ocular exposure to sulfur mustard (SM) vapor are the most prevalent chemical warfare injury. Ocular exposures exhibit three distinct, dose-dependent clinical trajectories: complete injury resolution, immediate transition to a chronic injury, or apparent recovery followed by the subsequent development of persistent ocular manifestations. These latter two trajectories include a constellation of corneal symptoms that are collectively known as mustard gas keratopathy (MGK). The etiology of MGK is not understood. Here, we synthesize recent findings from in vivo rabbit SM vapor studies, suggesting that tissue-specific damage during the acute injury can decrement the regenerative capacities of corneal endothelium and limbal stem cells, thereby predisposing the cornea to the chronic or delayed forms of MGK. This hypothesis not only provides a mechanism to explain the acute and MGK injuries but also identifies novel therapeutic modalities to mitigate or eliminate the acute and long-term consequences of ocular exposure to SM vapor. PMID:27310673

  14. Contact lens related corneal ulcer.

    PubMed

    Loh, Ky; Agarwal, P

    2010-01-01

    A corneal ulcer caused by infection is one of the major causes of blindness worldwide. One of the recent health concerns is the increasing incidence of corneal ulcers associated with contact lens user especially if the users fail to follow specific instruction in using their contact lenses. Risk factors associated with increased risk of contact lens related corneal ulcers are: overnight wear, long duration of continuous wear, lower socio-economic classes, smoking, dry eye and poor hygiene. The presenting symptoms of contact lens related corneal ulcers include eye discomfort, foreign body sensation and lacrimation. More serious symptoms are redness (especially circum-corneal injection), severe pain, photophobia, eye discharge and blurring of vision. The diagnosis is established by a thorough slit lamp microscopic examination with fluorescein staining and corneal scraping for Gram stain and culture of the infective organism. Delay in diagnosing and treatment can cause permanent blindness, therefore an early referral to ophthalmologist and commencing of antimicrobial therapy can prevent visual loss. PMID:25606178

  15. Corneal Collagen Cross-Linking

    PubMed Central

    Jankov II, Mirko R.; Jovanovic, Vesna; Nikolic, Ljubisa; Lake, Jonathan C.; Kymionis, Georgos; Coskunseven, Efekan

    2010-01-01

    Corneal collagen cross-linking (CXL) with riboflavin and ultraviolet-A (UVA) is a new technique of corneal tissue strengthening by using riboflavin as a photosensitizer and UVA to increase the formation of intra and interfibrillar covalent bonds by photosensitized oxidation. Keratocyte apoptosis in the anterior segment of the corneal stroma all the way down to a depth of about 300 microns has been described and a demarcation line between the treated and untreated cornea has been clearly shown. It is important to ensure that the cytotoxic threshold for the endothelium has not been exceeded by strictly respecting the minimal corneal thickness. Confocal microscopy studies show that repopulation of keratocytes is already visible 1 month after the treatment, reaching its pre-operative quantity and quality in terms of functional morphology within 6 months after the treatment. The major indication for the use of CXL is to inhibit the progression of corneal ectasias, such as keratoconus and pellucid marginal degeneration. CXL may also be effective in the treatment and prophylaxis of iatrogenic keratectasia, resulting from excessively aggressive photoablation. This treatment has also been used to treat infectious corneal ulcers with apparent favorable results. Combination with other treatments, such as intracorneal ring segment implantation, limited topography-guided photoablation and conductive keratoplasty have been used with different levels of success. PMID:20543933

  16. Intrastromal Corneal Ring Implants for Corneal Thinning Disorders

    PubMed Central

    2009-01-01

    Executive Summary Objective The purpose of this project was to determine the role of corneal implants in the management of corneal thinning disease conditions. An evidence-based review was conducted to determine the safety, effectiveness and durability of corneal implants for the management of corneal thinning disorders. The evolving directions of research in this area were also reviewed. Subject of the Evidence-Based Analysis The primary treatment objectives for corneal implants are to normalize corneal surface topography, improve contact lens tolerability, and restore visual acuity in order to delay or defer the need for corneal transplant. Implant placement is a minimally invasive procedure that is purported to be safe and effective. The procedure is also claimed to be adjustable, reversible, and both eyes can be treated at the same time. Further, implants do not limit the performance of subsequent surgical approaches or interfere with corneal transplant. The evidence for these claims is the focus of this review. The specific research questions for the evidence review were as follows: Safety Corneal Surface Topographic Effects: Effects on corneal surface remodelling Impact of these changes on subsequent interventions, particularly corneal transplantation (penetrating keratoplasty [PKP]) Visual Acuity Refractive Outcomes Visual Quality (Symptoms): such as contrast vision or decreased visual symptoms (halos, fluctuating vision) Contact lens tolerance Functional visual rehabilitation and quality of life Patient satisfaction: Disease Process: Impact on corneal thinning process Effect on delaying or deferring the need for corneal transplantation Clinical Need: Target Population and Condition Corneal ectasia (thinning) comprises a range of disorders involving either primary disease conditions such as keratoconus and pellucid marginal corneal degeneration or secondary iatrogenic conditions such as corneal thinning occurring after LASIK refractive surgery. The condition

  17. Acellular ostrich corneal stroma used as scaffold for construction of tissue-engineered cornea

    PubMed Central

    Liu, Xian-Ning; Zhu, Xiu-Ping; Wu, Jie; Wu, Zheng-Jie; Yin, Yong; Xiao, Xiang-Hua; Su, Xin; Kong, Bin; Pan, Shi-Yin; Yang, Hua; Cheng, Yan; An, Na; Mi, Sheng-Li

    2016-01-01

    AIM To assess acellular ostrich corneal matrix used as a scaffold to reconstruct a damaged cornea. METHODS A hypertonic saline solution combined with a digestion method was used to decellularize the ostrich cornea. The microstructure of the acellular corneal matrix was observed by transmission electron microscopy (TEM) and hematoxylin and eosin (H&E) staining. The mechanical properties were detected by a rheometer and a tension machine. The acellular corneal matrix was also transplanted into a rabbit cornea and cytokeratin 3 was used to check the immune phenotype. RESULTS The microstructure and mechanical properties of the ostrich cornea were well preserved after the decellularization process. In vitro, the methyl thiazolyl tetrazolium results revealed that extracts of the acellular ostrich corneas (AOCs) had no inhibitory effects on the proliferation of the corneal epithelial or endothelial cells or on the keratocytes. The rabbit lamellar keratoplasty showed that the transplanted AOCs were transparent and completely incorporated into the host cornea while corneal turbidity and graft dissolution occurred in the acellular porcine cornea (APC) transplantation. The phenotype of the reconstructed cornea was similar to a normal rabbit cornea with a high expression of cytokeratin 3 in the superficial epithelial cell layer. CONCLUSION We first used AOCs as scaffolds to reconstruct damaged corneas. Compared with porcine corneas, the anatomical structures of ostrich corneas are closer to those of human corneas. In accordance with the principle that structure determines function, a xenograft lamellar keratoplasty also confirmed that the AOC transplantation generated a superior outcome compared to that of the APC graft. PMID:27158598

  18. Corneal Pachymetry Mapping with High-speed Optical Coherence Tomography

    PubMed Central

    Li, Yan; Shekhar, Raj; Huang, David

    2006-01-01

    significant, but no more than the CCT measurement differences between ultrasound pachymeters. The reproducibility of the OCT zonal pachymetry averages was roughly 2 μm. Conclusions High-speed OCT provided noncontact, rapid, reproducible pachymetric mapping over a wide area of the cornea. It is equivalent to ultrasound for CCT measurement before and after LASIK. This technology could be valuable for planning keratorefractive procedures and diagnosis of corneal diseases. PMID:16650675

  19. An overview of corneal collagen cross-linking (CXL).

    PubMed

    Kymionis, George D; Mikropoulos, Dimitrios G; Portaliou, Dimitra M; Voudouragkaki, Irini C; Kozobolis, Vassilios P; Konstas, Anastasios G P

    2013-10-01

    Corneal collagen cross-linking (CXL) was first described over a decade ago and is now considered to be one of the most important surgical innovations of modern ophthalmology. Prior to its introduction, no interventions were available to arrest, or slow down ectatic disease progression, with corneal transplantation required in the majority of cases. Unlike earlier treatments of corneal ectasias that attempted to only improve the consequences of the disease, CXL aims to address the corneal biomechanical weakening itself. The long-term safety and efficacy of CXL have been established in several studies that have documented significant improvements in all outcome measures (visual acuity, spherical equivalent, astigmatism, and keratometric findings). The emerging combination of CXL with other interventions (termed 'CXL plus') optimizes the visual and topographic outcomes. This, along with the expansion of the techniques' indications for other clinical conditions, such as microbial keratitis, highlights the continuous improvement of the initial technique and confirms its wide acceptance. Overall, CXL has already demonstrated much promise and has several clinical indications, representing a clear example of recent advances in ocular therapy. PMID:24170589

  20. The Effect of Anterior Stromal Puncture Using Q-Switched Nd:YAG Laser on Corneal Wound Healing

    PubMed Central

    Hamdy Abdelaziz, Mohamed; Fouad Ghoneim, Dina; Abdelkawi Ahmed, Salwa; Taher, Ibraheim Mohyeldin; Abdel- Salam, Ahmed Medhat

    2014-01-01

    Introduction: Recurrent corneal erosion occurs when the wounded corneal epithelium failed to adhere to the underlying stroma. Therefore, this work aimed to assess the effect of treatment of corneal injury using Q- switched Nd:YAG laser. Method: Twenty one New Zealand male rabbits weighing 2-2.5 kg and 3 months old were classified into three main groups. The control group: did not received any treatment (n=3 rabbits). The rest of the animals (n= 18 rabbits), corneal epithelium was injured by syringe needle and blade 15 and divided into:(A) Normal healing group: which was divided into three subgroups (n=3 rabbits each), and the animals were left for normal healing for1 day, 1 week, and 4 weeks respectively, (B) Laser treated group: divided into three subgroups (n=3 rabbit seach) and subjected to anterior stromal puncture using Q-switched Nd: YAG laser on corneal sub-epithelium or superficial stroma, and the animals were left for 1 day, 1 week, and 4 weeksrespectively. After the demonstrated periods, the corneas were isolated for estimation of total protein content, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), total antioxidative capacity (TAC), total oxidative capacity (TOC) and oxidative stress index (OSI). Results: The present results of corneal total protein showed increment in the percentage change in normal healed groups after 1 day, 1 week and 4 weeks by values of 93%, 68% and 39%. In Q-switched Nd: YAG laser treated group the results showed better improvement in corneal protein than normal healed group with percentage changes of 58%, 29%, and 7.5% respectively. In SDS- PAGE, a protein band at 110 KD appeared in the migrating epithelium for both normal healed group and Q-switched Nd:YAG laser treated group with changes in the peaks intensities at middle and low molecular weight regions. Moreover, after 4 weeks the peak at 110 KD disappeared in the wounded epithelium treated with Q-switched Nd:YAG. After four weeks, the OSI in laser

  1. Topical Application of Naltrexone Facilitates Reepithelialization of the Cornea in Diabetic Rabbits

    PubMed Central

    Sassani, Joseph W.; Carroll, Melissa A.; McLaughlin, Patricia J.

    2009-01-01

    Delayed corneal re-epithelialization is a complication of diabetes, and may lead to ulcers and erosions, which cause ocular morbidity and visual loss. This study examined the efficacy of naltrexone (NTX), a long-acting, potent opioid antagonist, applied topically, to facilitate the repair of standarized corneal abrasions in diabetic (alloxan-induced) New Zealand white rabbits (glucose levels). NTX at a concentration of 10−4 M, or sterile vehicle (SV), was administered topically 4 times per day for 7 days to the abraded eye of uncontrolled type 1 diabetic (DB), insulin-controlled type 1 diabetic (DB-IN), or nondiabetic (Normal) rabbits. Wound healing was monitored, and noninvasive (tonopen, pachymeter, hand-held slit lamp, and retinal camera) and invasive (histopathology) measurements evaluated. Corneal re-epithelialization in the uncontrolled DB rabbits was significantly enhanced (up to a 47% reduction in wound area) following treatment with NTX relative to both Normal SV and DB SV rabbits at 24, 48, and 56 hr following surgery. At 72 hr, DB NTX rabbits had residual defects that were 64%–82% smaller than Normal and DB SV animals. NTX treated DB-IN rabbits had residual defects that were 9–37% smaller than DB-IN rabbits receiving SV, and 6–40% smaller than Normal rabbits. No signs of toxicity from topical applications were noted. These data confirm and extend those documented in rats that demonstrated a lack of toxicity of NTX at a wide range of dosages, as well as efficacy for enhanced corneal epithelialization. These studies set the stage for clinical trials using NTX as a therapy for diabetic keratopathy. PMID:19853024

  2. Effects of morphine on corneal sensitivity and epithelial wound healing: implications for topical ophthalmic analgesia.

    PubMed Central

    Peyman, G A; Rahimy, M H; Fernandes, M L

    1994-01-01

    Studies were conducted to examine the analgesic and toxic effects of topical morphine on corneal abrasion. For the toxicity study, rabbits were anaesthetized and epithelial cells were removed from the cornea and limbus. Animals were randomised and treated topically as follows: (1) saline (control); (2) morphine sulphate (MS, 0.5%); and (3) proxymetacaine hydrochloride (proparacaine) (PH, 0.5%). Two drops of the solution were instilled in the eyes at 4 hour intervals for 6 consecutive days and the progression of corneal wound healing was assessed. Results showed that repeated topical MS had no adverse effects on corneal wound closure. The rates of wound healing were similar in both saline and MS treated groups. Eyes treated with MS showed wound closure in a symmetrical fashion starting on day 2 following abrasion. The progression of epithelial wound healing was completed by day 4 in one eye, by day 5 in three eyes, and by day 7 in five eyes. In contrast, repeated topical PH application delayed corneal wound closure. Eyes treated with PH showed signs of corneal wound closure on the third day, but only two eyes out of six had completed wound closure by the eighth day after corneal abrasion. In a subsequent masked study, the analgesic efficacy of topical MS was assessed in seven patients with unilateral corneal abrasion. In all cases, a baseline response was first established. Subsequently, saline was instilled in both eyes and the patient's corneal response to pain pressure was determined 10 and 20 minutes later. Finally, MS was applied and the analgesic effect on the cornea was assessed. Results showed that saline had no effect compared with the baseline response. In contrast, MS showed an analgesic effect as early as 10 minutes after application in the eye with corneal abrasion. MS showed an analgesic efficacy of 4.3-fold and 5.5-fold greater than the baseline or saline on the eye with corneal abrasion. However, MS had no analgesic effect on the intact corneal

  3. Substrates for Expansion of Corneal Endothelial Cells towards Bioengineering of Human Corneal Endothelium

    PubMed Central

    Navaratnam, Jesintha; Utheim, Tor P.; Rajasekhar, Vinagolu K.; Shahdadfar, Aboulghassem

    2015-01-01

    Corneal endothelium is a single layer of specialized cells that lines the posterior surface of cornea and maintains corneal hydration and corneal transparency essential for vision. Currently, transplantation is the only therapeutic option for diseases affecting the corneal endothelium. Transplantation of corneal endothelium, called endothelial keratoplasty, is widely used for corneal endothelial diseases. However, corneal transplantation is limited by global donor shortage. Therefore, there is a need to overcome the deficiency of sufficient donor corneal tissue. New approaches are being explored to engineer corneal tissues such that sufficient amount of corneal endothelium becomes available to offset the present shortage of functional cornea. Although human corneal endothelial cells have limited proliferative capacity in vivo, several laboratories have been successful in in vitro expansion of human corneal endothelial cells. Here we provide a comprehensive analysis of different substrates employed for in vitro cultivation of human corneal endothelial cells. Advances and emerging challenges with ex vivo cultured corneal endothelial layer for the ultimate goal of therapeutic replacement of dysfunctional corneal endothelium in humans with functional corneal endothelium are also presented. PMID:26378588

  4. Traumatic corneal endothelial rings from homemade explosives.

    PubMed

    Ng, Soo Khai; Rudkin, Adam K; Galanopoulos, Anna

    2013-08-01

    Traumatic corneal endothelial rings are remarkably rare ocular findings that may result from blast injury. We present a unique case of bilateral traumatic corneal endothelial rings secondary to blast injury from homemade explosives. PMID:23474743

  5. Corneal temperature in schizophrenia patients.

    PubMed

    Shiloh, Roni; Munitz, Hanan; Portuguese, Shirley; Gross-Isseroff, Ruth; Sigler, Mayanit; Bodinger, Liron; Katz, Nachum; Stryjer, Rafael; Hermesh, Haggai; Weizman, Abraham

    2005-12-01

    Most data imply that dopaminergic transmission is essential for proper hypothalamic-mediated core temperature regulation. Altered central dopaminergic transmission is suggested to be involved in the pathophysiology of schizophrenia. Thus, hypothetically, schizophrenia patients might be at increased risk of developing thermoregulatory dysregulation manifested by alterations in core temperature, as well as in peripheral tissue, the temperature of which has been shown to correlate with core temperature (e.g. cornea). Previous small pilot studies of ours showed that schizophrenia patients may exhibit corneal temperature abnormalities. Hence, we assessed corneal temperature in a controlled sample of drug-free ( n =11) and medicated ( n =28) schizophrenia patients compared to healthy comparison subjects ( n =9), using a FLIR thermal imaging camera. Drug-free schizophrenia patients exhibited significantly higher corneal temperature compared to healthy subjects, typical antipsychotic drug (APD)-treated patients ( n =16) and atypical APD-treated patients ( n =12) (37.08+/-1.46 degrees C vs. 33.37+/-2.51 degrees C, 31.08+/-1.43 degrees C and 31.67+/-0.44 degrees C respectively, p <0.0001; p <0.001 vs. each group separately). The healthy comparison subjects and the atypical APD-treated patients exhibited comparable corneal temperatures and these two groups exhibited higher corneal temperatures compared to the typical APD-treated patients ( p <0.01 and p =0.051 respectively). In conclusion, this study indicates that drug-free schizophrenia patients exhibit substantially higher corneal temperature compared to healthy comparison subjects or medicated patients, and that APDs may decrease corneal temperature either to normal (atypical APD) or to subnormal (typical APD) values. The relevance of these phenomena to the pathophysiology of schizophrenia, the biological mechanism underlying drug-induced corneal temperature alterations, the possible role of temperature-lowering drugs

  6. Effect of Glyceraldehyde Cross-Linking on a Rabbit Bullous Keratopathy Model

    PubMed Central

    Wang, Mengmeng

    2015-01-01

    Background. To evaluate the effects of corneal glyceraldehyde CXL on the rabbit bullous keratopathy models established by descemetorhexis. Methods. Fifteen rabbits were randomly divided into five groups. Group A (n = 3) is the control group. The right eyes of animals in Groups B,C, D, and E (n = 3, resp.) were suffered with descemetorhexis procedures. From the 8th day to the 14th day postoperatively, the right eyes in Groups C and D were instilled with hyperosmolar drops and glyceraldehyde drops, respectively; the right eyes in Group E were instilled with both hyperosmolar drops and glyceraldehyde drops. Central corneal thickness (CCT), corneal transparency score, and histopathological analysis were applied on the eyes in each group. Results. Compared with Group A, statistically significant increase in CCT and corneal transparency score was found in Groups B, C, D, and E at 7 d postoperatively (P < 0.05) and in Groups C, D, and E at 14 d postoperatively (P < 0.05). Conclusion. Chemical CXL technique using glyceraldehyde improved the CCT and corneal transparency of the rabbit bullous keratopathy models. Topical instillation with glyceraldehyde and hyperosmolar solutions seems to be a good choice for the bullous keratopathy treatment. PMID:26509077

  7. Assessment of corneal hydration sensing in the terahertz band: in vivo results at 100 GHz

    PubMed Central

    Taylor, Zachary; Tewari, Pria; Sung, Shijun; Maccabi, Ashkan; Singh, Rahul; Culjat, Martin; Grundfest, Warren; Hubschman, Jean-Pierre; Brown, Elliott

    2012-01-01

    Abstract. Terahertz corneal hydration sensing has shown promise in ophthalmology applications and was recently shown to be capable of detecting water concentration changes of about two parts in a thousand in ex vivo corneal tissues. This technology may be effective in patient monitoring during refractive surgery and for early diagnosis and treatment monitoring in diseases of the cornea. In this work, Fuchs dystrophy, cornea transplant rejection, and keratoconus are discussed, and a hydration sensitivity of about one part in a hundred is predicted to be needed to successfully distinguish between diseased and healthy tissues in these applications. Stratified models of corneal tissue reflectivity are developed and validated using ex vivo spectroscopy of harvested porcine corneas that are hydrated using polyethylene glycol solutions. Simulation of the cornea’s depth-dependent hydration profile, from 0.01 to 100 THz, identifies a peak in intrinsic reflectivity contrast for sensing at 100 GHz. A 100 GHz hydration sensing system is evaluated alongside the current standard ultrasound pachymetry technique to measure corneal hydration in vivo in four rabbits. A hydration sensitivity, of three parts per thousand or better, was measured in all four rabbits under study. This work presents the first in vivo demonstration of remote corneal hydration sensing. PMID:23085925

  8. Biocompatibility and drug release behavior of chitosan/poly (vinyl alcohol) corneal shield in vivo

    PubMed Central

    Li, Guo-Xing; Gu, Xin; Song, Hui-Yang; Nan, Kai-Hui; Chen, Hao

    2015-01-01

    Backgound: Chitosan/polyvinyl alcohol corneal cap has good biocompatibility and drug slow release characteristics, which provided new treatment method for anterior segment disease. Our study was to evaluate biocompatibility of poly (vinyl alcohol)/chitosan corneal shield’s intraocular and investigate its feasibility to treat ocular surface disorders. Methods: Thirty-six white rabbits were randomly divided into four groups. Slit lamp observation were conducted at 1, 3, 7 and 10 days after operation. Corneal and conjunctiva tissue harvested from the experimental groups was observed by HE staining 10 days after operation. The aqueous humor was aspirated from the anterior chamber at each designated time point (1, 3, 7 and 10 days). The cornea and conjunctive were collected at 10 days. The concentration of each tissue was analyzed by ultra-performance liquid chromatography and microscope observation. Results: In all groups, mild hyperemia was observed 1 day after operation, and there was no obvious inflammatory reaction occurring on the seventh and tenth day. No corneal edema and inflammatory reaction of anterior chamber occurred till the tenth day. For histopathology, there was no obviously mild chronic and inflammatory reaction occurred, and no significant difference between the corneal shield with-in groups and with-out groups. The drug concentrations in corneal and conjunctival in group (A, B) were significantly lower than eye drops in the control group (C, D), and blank corneal cover in group C was significantly sham operation in group D. Conclusion: The results indicated that the proposed membrane combined with ophthalmic solution has substantial potential as ocular delivery system. PMID:26550213

  9. Quantitative Assessment of UVA-Riboflavin Corneal Cross-Linking Using Nonlinear Optical Microscopy

    PubMed Central

    Chai, Dongyul; Gaster, Ronald N.; Roizenblatt, Roberto; Juhasz, Tibor; Brown, Donald J.

    2011-01-01

    Purpose. Corneal collagen cross-linking (CXL) by the use of riboflavin and ultraviolet-A light (UVA) is a promising and novel treatment for keratoconus and other ectatic disorders. Since CXL results in enhanced corneal stiffness, this study tested the hypothesis that CXL-induced stiffening would be proportional to the collagen autofluorescence intensity measured with nonlinear optical (NLO) microscopy. Methods. Rabbit eyes (n = 50) were separated into five groups including: (1) epithelium intact; (2) epithelium removed; (3) epithelium removed and soaked in riboflavin, (4) epithelium removed and soaked in riboflavin, with 15 minutes of UVA exposure; and (5) epithelium removed and soaked in riboflavin, with 30 minutes of UVA exposure. Corneal stiffness was quantified by measuring the force required to displace the cornea 500 μm. Corneas were then fixed in paraformaldehyde and sectioned, and the collagen autofluorescence over the 400- to 450-nm spectrum was recorded. Results. There was no significant difference in corneal stiffness among the three control groups. Corneal stiffness was significantly and dose dependently increased after UVA (P < 0.0005). Autofluorescence was detected only within the anterior stroma of the UVA-treated groups, with no significant difference in the depth of autofluorescence between different UVA exposure levels. The signal intensity was also significantly increased with longer UVA exposure (P < 0.001). Comparing corneal stiffness with autofluorescence intensity revealed a significant correlation between these values (R2 = 0.654; P < 0.0001). Conclusions. The results of this study indicate a significant correlation between corneal stiffening and the intensity of collagen autofluorescence after CXL. This finding suggests that the efficacy of CXL in patients could be monitored by assessing collagen autofluorescence. PMID:21508101

  10. Corneal collagen crosslinking in keratoconus and other eye disease

    PubMed Central

    Alhayek, Adel; Lu, Pei-Rong

    2015-01-01

    Keratoconus is a condition characterized by biomechanical instability of the cornea, presenting in a progressive, asymmetric and bilateral way. Corneal collagen crosslinking (CXL) with riboflavin and Ultraviolet-A (UVA) is a new technique of corneal tissue strengthening that combines the use of riboflavin as a photo sensitizer and UVA irradiation. Studies showed that CXL was effective in halting the progression of keratoconus over a period of up to four years. The published studies also revealed a reduction of max K readings by more than 2 D, while the postoperative spherical equivalent (SEQ) was reduced by an average of more than 1 D and refractive cylinder decreased by about 1 D. The major indication for the use of CXL is to inhibit the progression of corneal ecstasies, such as keratoconus and pellucid marginal degeneration. CXL may also be effective in the treatment and prophylaxis of iatrogenic keratectasia, resulting from excessively aggressive photo ablation. This treatment has been used to treat infectious corneal ulcers with apparent favorable results. Most recent studies demonstrate the beneficial impact of CXL for iatrogenic ecstasies, pellucid marginal degeneration, infectious keratitis, bullous keratopathy and ulcerative keratitis. Several long-term and short-term complications of CXL have been studied and documented. The possibility of a secondary infection after the procedure exists because the patient is subject to epithelial debridement and the application of a soft contact lens. Formation of temporary corneal haze, permanent scars, endothelial damage, treatment failure, sterile infiltrates, bullous keratopathy and herpes reactivation are the other reported complications of this procedure. PMID:25938065

  11. Natural corneal cell-based microenvironment as prerequisite for balanced 3D corneal epithelial morphogenesis: a promising animal experiment-abandoning tool in ophthalmology.

    PubMed

    Schulz, Simon; Beck, David; Laird, Dougal; Steinberg, Thorsten; Tomakidi, Pascal; Reinhard, Thomas; Eberwein, Philipp

    2014-04-01

    To achieve durable recognition as a promising animal experiment-abandoning tool in ophthalmology, in vitro engineered tissue equivalents of the human cornea should exhibit proper morphogenesis. Regarding this issue, we were seeking for the natural cell microenvironment fulfilling the minimum requirements to allow human corneal keratinocytes to develop a balanced epithelial morphology with regular spatial appearance of tissue homeostatic biomarkers. Hence, we established cocultures of 3D cell-based collagen scaffolds comprising immortalized corneal keratinocytes combined with a gradual cornea-derived in vivo-like cell microenvironment, together with immortalized stromal fibroblasts alone (nonholistic) or fibroblasts and immortalized endothelial cells (holistic). With matched non-holistic microenvironments revealing mostly flattened cells and putative apical cell ablation foci at day 6, and 9 in HE stains, holistic counterparts yielded proper epithelial stratification with cell flattening restricted to apical layers. Concordantly, RT(2)-PCR showed a tremendous increase in gene expression for progressive and terminal biomarkers of corneal keratinocyte differentiation, cytokeratin (CK) 12, and filaggrin (FIL), in response to nonholistic environments, while involucrin (INV) was moderately but significantly upregulated. Although visible, this increase was moderate in corneal keratinocytes with a holistic environment. On the protein level, indirect immunofluorescence revealed that only epithelia of holistic environments showed diminishment in CK19, counteracted by CK12 rising over time. This time-dependent progression in differentiation coincided with declined proliferation and tissue-regular focus of differentiation biomarkers inv and fil to suprabasal and apical cell layers. Our novel findings suggest the interplay of native tissue forming cell entities, important for balanced corneal epithelial morphogenesis. In addition, they provide evidence for a holistic cell

  12. Gene Therapy in Corneal Transplantation

    PubMed Central

    Qazi, Yureeda; Hamrah, Pedram

    2014-01-01

    Corneal transplantation is the most commonly performed organ transplantation. Immune privilege of the cornea is widely recognized, partly because of the relatively favorable outcome of corneal grafts. The first-time recipient of corneal allografts in an avascular, low-risk setting can expect a 90% success rate without systemic immunosuppressive agents and histocompatibility matching. However, immunologic rejection remains the major cause of graft failure, particularly in patients with a high risk for rejection. Corticosteroids remain the first-line therapy for the prevention and treatment of immune rejection. However, current pharmacological measures are limited in their side-effect profiles, repeated application, lack of targeted response, and short duration of action. Experimental ocular gene therapy may thus present new horizons in immunomodulation. From efficient viral vectors to sustainable alternative splicing, we discuss the progress of gene therapy in promoting graft survival and postulate further avenues for gene-mediated prevention of allogeneic graft rejection. PMID:24138037

  13. Corneal neovascularization and biological therapy

    PubMed Central

    Voiculescu, OB; Voinea, LM; Alexandrescu, C

    2015-01-01

    Corneal avascularity is necessary for the preservation of optimal vision. The cornea maintains a dynamic balance between pro- and antiangiogenic factors that allows it to remain avascular under normal homeostatic conditions. Corneal neovascularization (NV) is a condition that can develop in response to inflammation, hypoxia, trauma, or limbal stem cell deficiency and it is a significant cause of blindness. New therapeutic options for diseases of the cornea and ocular surface are now being explored in experimental animals and clinical trials. Antibody based biologics are being tested for their ability to reduce blood and lymphatic vessel ingrowth into the cornea, and to reduce inflammation. Numerous studies have shown that biologics with specificity for VEGF A such as bevacizumab and ranibizumab (a recombinant antibody and an antibody fragment, respectively) or anti-tumor necrosis factor-α microantibody, are effective in the treatment of corneal neovascularization. PMID:26664467

  14. 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.

  15. [The cicatrization of corneal wounds].

    PubMed

    Spineanu, L

    1995-01-01

    The tissular mending of the corneal surface is the result of a complex series of various physiopathological responses. This structural regeneration involves a primary reconstruction and a secondary one. The primary reconstruction of the barrier function provides the restoring of the normal equilibrium of osmotic, thermal and metabolic exchanges. The primary cicatricial response's goal is the fast coating of the corneal plague and mainly involves an inflammatory response. The major stages of this initial sequence are: the migration of the polynuclear neutrophils into the plaque, the establishment of a fibrinous cork, the collapsing and then the migration of the epithelial cork, and the contraction of the keratocyte mesh. PMID:7577908

  16. 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

  17. Precision Measurement Of Corneal Topography

    NASA Astrophysics Data System (ADS)

    Yoder, Paul R.; Macri, Timothy F.; Telfair, William B.; Bennett, Peter S.; Martin, Clifford A.; Warner, John W.

    1989-05-01

    We describe a new electro-optical device being developed to provide precise measurements of the three-dimensional topography of the human cornea. This device, called a digital keratoscope, is intended primarily for use in preparing for and determining the effect of corneal surgery procedures such as laser refractive keratectomy, radial keratotomy or corneal transplant on the refractive power of the cornea. It also may serve as an aid in prescribing contact lenses. The basic design features of the hardware and of the associated computer software are discussed, the means for alignment and calibration are described and typical results are given.

  18. 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. PMID:25444646

  19. 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. PMID:25112897

  20. 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

  1. Observation on ultrastructure and histopathology of cornea following femtosecond laser-assisted deep lamellar keratoplasty for acute corneal alkaline burns

    PubMed Central

    Li, Wen-Jing; Hu, Yu-Kun; Song, Hui; Gao, Xiao-Wei; Zhao, Xu-Dong; Dong, Jing; Guo, Yun-Lin; Cai, Yan

    2016-01-01

    AIM To demonstrate the changes in ultrastructure and histopathology of the cornea in acute corneal alkaline burns after femtosecond laser-assisted deep lamellar keratoplasty. METHODS The New Zealand white rabbits treated with alkaline corneal burn were randomized into two groups, Group A (16 eyes) with femtosecond laser-assisted deep lamellar keratoplasty 24h after burn and Group B (16 eyes) without keratoplasty as controls. All eyes were evaluated with transmission electron microscopy (TEM) at 1, 2, 3, and 4wk follow-up, then all corneas were tested by hematoxylin and eosin staining histology. RESULTS The corneal grafts in Group A were transparent, while those in Group B showed corneal stromal edema and loosely arranged collagen fibers. One week after treatment, TEM revealed the intercellular desmosomes in the epithelial layers and intact non-dissolving nuclei in Group A. At week 4, the center of the corneas in Group A was transparent with regularly arranged collagen fibers and fibroblasts in the stroma. In Group B, squamous cells were observed on the corneal surface and some epithelial cells were detached. CONCLUSION Femtosecond laser-assisted deep lamellar keratoplasty can suppress inflammatory responses, prevent toxic substance-induced injury to the corneal endothelium and inner tissues with quicker recovery and better visual outcomes. PMID:27162716

  2. Decrease in Corneal Damage due to Benzalkonium Chloride by the Addition of Mannitol into Timolol Maleate Eye Drops.

    PubMed

    Nagai, Noriaki; Yoshioka, Chiaki; Tanino, Tadatoshi; Ito, Yoshimasa; Okamoto, Norio; Shimomura, Yoshikazu

    2015-01-01

    We investigated the protective effects of mannitol on corneal damage caused by benzalkonium chloride (BAC), which is used as a preservative in commercially available timolol maleate eye drops, using rat debrided corneal epithelium and a human cornea epithelial cell line (HCE-T). Corneal wounds were monitored using a fundus camera TRC-50X equipped with a digital camera; eye drops were instilled into rat eyes five times a day after corneal epithelial abrasion. The viability of HCE-T cells was calculated by TetraColor One; and Escherichia coli (ATCC 8739) were used to measure antimicrobial activity. The reducing effects on transcorneal penetration and intraocular pressure (IOP) of the eye drops were determined using rabbits. The corneal wound healing rate and rate constant (kH), as well as cell viability, were higher following treatment with 0.005% BAC solution containing 0.5% mannitol than in the case BAC solution alone; the antimicrobial activity was approximately the same for BAC solutions with and without mannitol. In addition, the kH for rat eyes instilled with commercially available timolol maleate eye drops containing 0.5% mannitol was significantly higher than that for eyes instilled with timolol maleate eye drops without mannitol, and the addition of mannitol did not affect the corneal penetration or IOP reducing effect of the timolol maleate eye drops. A preservative system comprising BAC and mannitol may provide effective therapy for glaucoma patients requiring long-term treatment with anti-glaucoma agents. PMID:26136174

  3. Decrease in corneal damage due to benzalkonium chloride by the addition of sericin into timolol maleate eye drops.

    PubMed

    Nagai, Noriaki; Ito, Yoshimasa; Okamoto, Norio; Shimomura, Yoshikazu

    2013-01-01

    We investigated the protective effects of sericin on corneal damage due to benzalkonium chloride (BAC) used as a preservative in commercially available timolol maleate eye drops using rat debrided corneal epithelium and a human cornea epithelial cell line (HCE-T). Corneal wounds were monitored using a fundus camera TRC-50X equipped with a digital camera; eye drops were instilled into the rat eyes five times a day after corneal epithelial abrasion. The viability of HCE-T cells was calculated by TetraColor One; and Escherichia coli (ATCC 8739) were used to measure antimicrobial activity. The reducing effects on transcorneal penetration and intraocular pressure (IOP) of the eye drops were determined using rabbits. The corneal wound healing rate and rate constants (kH) as well as cell viability were higher following treatment with 0.005% BAC solution containing 0.1% sericin than in the case of treatment with BAC solution alone; the antimicrobial activity was approximately the same for BAC solutions with and without sericin. In addition, the kH for rat eyes instilled with commercially available timolol maleate eye drops containing 0.1% sericin was significantly higher than that of eyes instilled with timolol maleate eye drops without sericin, and the addition of sericin did not affect the corneal penetration or IOP reducing effect of commercially available timolol maleate eye drops. A preservative system comprising BAC and sericin may provide effective therapy for glaucoma patients requiring long-term anti-glaucoma agents. PMID:23470443

  4. ITF2357 transactivates Id3 and regulate TGFβ/BMP7 signaling pathways to attenuate corneal fibrosis

    PubMed Central

    Lim, Rayne R.; Tan, Alison; Liu, Yu-Chi; Barathi, Veluchamy A.; Mohan, Rajiv R.; Mehta, Jodhbir S.; Chaurasia, Shyam S.

    2016-01-01

    Corneal fibrosis is often seen in patients with ocular trauma and infection that compromises corneal transparency resulting in vision loss. Treatment strategies including NSAIDs, steroids, MMC and corneal transplants have shown tremendous success but with several side effects and cellular toxicity. Histone deacetylase inhibitors (HDACi) have been shown to inhibit corneal fibrosis via TGFβ signaling pathway. In this study, we investigated safety, efficacy and mechanism of action of a HDACi, ITF2357 in TGFβ-stimulated in vitro primary human cornea stromal fibroblasts (pHCSFs) and in vivo in a photorefractive keratectomy-treated rabbit model of corneal fibrosis. We found that in vivo ITF2357 decreased collagen I, collagen IV, fibronectin, integrin αVβ3 expression with a reduction in corneal haze. In addition, ITF2357 reduced myofibroblast formation, suppressed phosphorylation of Smad proteins in TGFβ pathway and inhibited key responsive protein, P4HA1 involved in pro-collagen synthesis. Treatment of pHCSFs with ITF2357 activated BMP7 levels and expressed all the members of inhibitor of differentiation proteins (Id1-Id4), however, it failed to rescue TGFβ-driven transdifferentiation of fibroblasts to myofibroblasts in the presence of siRNA specific to Id3. We conclude that ITF2357 is a potential anti-fibrotic drug that exerts its action via activation of Id3, a downstream target of TGFβ/BMP7 signaling pathways. PMID:26865052

  5. RGTA-based matrix therapy in severe experimental corneal lesions: safety and efficacy studies.

    PubMed

    Brignole-Baudouin, F; Warnet, J M; Barritault, D; Baudouin, C

    2013-11-01

    Corneal alteration potentially leading to ulceration remains a major health concern in ocular surface diseases. A treatment that would improve both the quality and speed of healing and control the inflammation would be of great interest. Regenerating agents (RGTAs) have been shown to stimulate wound healing and modulate undesired fibrosis in various in vivo systems. We investigated the effects of RGTA-OTR4120(®) in a rabbit corneal model in order to assess its potential use in ocular surface diseases. First, we assessed its safety for 7 and 28 days using the Draize test criteria in healthy rabbit eyes; then, we investigated the effect of a single dose (50μl, 5μg) in an alkali-burned cornea model. Daily follow-up of clinical signs of healing was scored, and histology was performed at D7. RGTA was well tolerated; no signs of ocular irritation were observed. In the corneal alkali-burn model, non-RGTA-treated eyes showed inflammatory clinical signs, and histology confirmed a loss of superficial corneal layers with epithelial disorganization, neovascularization and infiltration of inflammatory cells. When compared to NaCl control, RGTA treatment appeared effective in reducing clinical signs of inflammation, enhancing re-epithelialization, and improving histological patterns: edema, fibrosis, neovascularization and inflammation. Three to four layers of epithelial cells were already organized, stroma was virtually unvascularized and keratocytes well implanted in parallel collagen fibers with an overall reorganization similar to normal cornea. RGTA appears to be a promising agent for controlling ocular surface inflammation and promoting corneal healing and was well tolerated. This study offers preclinical information and supports the findings of other (compassionate or pilot) studies conducted in patients with various ocular surface diseases. PMID:23958066

  6. [Current treatments for corneal neovascularization].

    PubMed

    Benayoun, Y; Petellat, F; Leclerc, O; Dost, L; Dallaudière, B; Reddy, C; Robert, P-Y; Salomon, J-L

    2015-12-01

    The extension of blood vessels into the normally avascular stroma defines corneal neovascularization. Though this phenomenon, pathophysiological and clinical features are well characterized, therapeutic modalities have been hindered by a lack of safe, efficacious and non-controversial treatments. In this literature review, we focus on available therapeutic options in light of recent evidence provided by animal and clinical studies. First, this review will focus on pharmacological treatments that target angiogenesis. The low cost and market availability of bevacizumab make it the first anti-angiogenic therapy choice, and it has demonstrable efficacy in reducing corneal neovascularization when administered topically or subconjunctivally. However, novel anti-angiogenic molecules targeting the intracellular pathways of angiogenesis (siRNA, antisense oligonucleotides) provide a promising alternative. Laser therapy (direct photocoagulation or photo-dynamic therapy) and fine needle diathermy also find a place in the treatment of stabilized corneal neovascularization alone or in association with anti-angiogenic therapy. Additionally, ocular surface reconstruction using amniotic membrane graft or limbal stem cell transplantation is essential when corneal neovascularization is secondary to primary or acquired limbal deficiency. PMID:26522890

  7. Immunological aspects of corneal transplant.

    PubMed

    Kumar, Vijay; Kumar, Asha

    2014-01-01

    Corneal transplant is the most common solid tissue transplant in humans. Advances in microsurgical techniques, eye banking and the use of corticosteroids have improved the success of corneal transplants. Over 65,000 corneal transplants are being performed worldwide annually. Most of these transplants are performed in developed countries. Cornea is considered an immune privileged site. Despite this, immune mediated graft rejection is the most single cause of cornea graft failure and is one of the major postoperative complications. Incidences from as low as 2% to as high as 50% have been reported depending upon the degree of vascularization. Rejection involves donor tissue recognition and various factors may influence this rejection. Major factors include the antigenic load of the donor tissue; other factors include death to enucleation time, methods and temperature of preserving the tissue. Host factors that may impact the graft include ocular surface diseases such as dry eye, chemical burns and autoimmune diseases such as mucous membrane pemphigoid. Following infection, surgery or trauma, cells of the innate immune system invade the cornea as a result of up-regulation of cytokines, cellular adhesion molecules and growth and angiogenic factors. These factors results in neoangiogenesis and lymphoangiogenesis, leading to immune activation and graft rejection. The various immunological mechanisms that may play a role in the corneal transplant are discussed. PMID:25296240

  8. Fate Mapping Mammalian Corneal Epithelia.

    PubMed

    Richardson, Alexander; Wakefield, Denis; Di Girolamo, Nick

    2016-04-01

    The anterior aspect of the cornea consists of a stratified squamous epithelium, thought to be maintained by a rare population of stem cells (SCs) that reside in the limbal transition zone. Although migration of cells that replenish the corneal epithelium has been studied for over a century, the process is still poorly understood and not well characterized. Numerous techniques have been employed to examine corneal epithelial dynamics, including visualization by light microscopy, the incorporation of vital dyes and DNA labels, and transplantation of genetically marked cells that have acted as cell and lineage beacons. Modern-day lineage tracing utilizes molecular methods to determine the fate of a specific cell and its progeny over time. Classically employed in developmental biology, lineage tracing has been used more recently to track the progeny of adult SCs in a number of organs to pin-point their location and understand their movement and influence on tissue regeneration. This review highlights key discoveries that have led researchers to develop cutting-edge genetic tools to effectively and more accurately monitor turnover and displacement of cells within the mammalian corneal epithelium. Collating information on the basic biology of SCs will have clinical ramifications in furthering our knowledge of the processes that govern their role in homeostasis, wound-healing, transplantation, and how we can improve current unsatisfactory SC-based therapies for patients suffering blinding corneal disease. PMID:26774909

  9. Corneal Stroma Microfibrils

    PubMed Central

    Hanlon, Samuel D.; Behzad, Ali R.; Sakai, Lynn Y.; Burns, Alan R.

    2015-01-01

    Elastic tissue was first described well over a hundred years ago and has since been identified in nearly every part of the body. In this review, we examine elastic tissue in the corneal stroma with some mention of other ocular structures which have been more thoroughly described in the past. True elastic fibers consist of an elastin core surrounded by fibrillin microfibrils. However, the presence of elastin fibers is not a requirement and some elastic tissue is comprised of non-elastin-containing bundles of microfibrils. Fibers containing a higher relative amount of elastin are associated with greater elasticity and those without elastin, with structural support. Recently it has been shown that the microfibrils, not only serve mechanical roles, but are also involved in cell signaling through force transduction and the release of TGF-β. A well characterized example of elastin-free microfibril bundles (EFMBs) is found in the ciliary zonules which suspend the crystalline lens in the eye. Through contraction of the ciliary muscle they exert enough force to reshape the lens and thereby change its focal point. It is believed that the molecules comprising these fibers do not turn-over and yet retain their tensile strength for the life of the animal. The mechanical properties of the cornea (strength, elasticity, resiliency) would suggest that EFMBs are present there as well. However, many authors have reported that, although present during embryonic and early postnatal development, EFMBs are generally not present in adults. Serial-block-face imaging with a scanning electron microscope enabled 3D reconstruction of elements in murine corneas. Among these elements were found fibers that formed an extensive network throughout the cornea. In single sections these fibers appeared as electron dense patches. Transmission electron microscopy provided additional detail of these patches and showed them to be composed of fibrils (∼10nm diameter). Immunogold evidence clearly

  10. Intrastromal Injection of China Painting Ink in Corneas of Male Rabbits: Clinical and Histological Study.

    PubMed

    Alsmman Hassan, Alahmady Hamad; Abd Elhaliem Soliman, Nesreen Gamal-Eldeen

    2016-01-01

    Background. Many patients with corneal opacity or complicated cataract in blind eye ask for cosmoses. In this study we tried to investigate the staining of corneas of male rabbits by Rotring China painting ink and to study the histological changes. Method. 10 eyes of 10 male Baladi Egyptian rabbits were injected (0.1 mL) intrastromally in the cornea by the use of China painting ink (Rotring Tinta China) through insulin syringe (27-gauge needle) by single injection; clinical follow-up is for 6 months and lastly the rabbits were scarified and the stained eyes were enucleated for histological analysis. Results. Clinically the stain was stable in color and distribution in corneas with no major complications. Histological results of the stained rabbit corneas showed blackish pigmentation in the corneal stroma without any inflammatory cellular infiltration. Some fibroblast cells had pigment granules in their cytoplasm in the adjacent layers. Conclusion. Corneal staining by China painting ink is effective and safe in staining of male rabbits cornea; however further study in human corneas with longer follow-up period is advisable. PMID:27195146

  11. Intrastromal Injection of China Painting Ink in Corneas of Male Rabbits: Clinical and Histological Study

    PubMed Central

    Alsmman Hassan, Alahmady Hamad; Abd Elhaliem Soliman, Nesreen Gamal-Eldeen

    2016-01-01

    Background. Many patients with corneal opacity or complicated cataract in blind eye ask for cosmoses. In this study we tried to investigate the staining of corneas of male rabbits by Rotring China painting ink and to study the histological changes. Method. 10 eyes of 10 male Baladi Egyptian rabbits were injected (0.1 mL) intrastromally in the cornea by the use of China painting ink (Rotring Tinta China) through insulin syringe (27-gauge needle) by single injection; clinical follow-up is for 6 months and lastly the rabbits were scarified and the stained eyes were enucleated for histological analysis. Results. Clinically the stain was stable in color and distribution in corneas with no major complications. Histological results of the stained rabbit corneas showed blackish pigmentation in the corneal stroma without any inflammatory cellular infiltration. Some fibroblast cells had pigment granules in their cytoplasm in the adjacent layers. Conclusion. Corneal staining by China painting ink is effective and safe in staining of male rabbits cornea; however further study in human corneas with longer follow-up period is advisable. PMID:27195146

  12. Imaging, Reconstruction, And Display Of Corneal Topography

    NASA Astrophysics Data System (ADS)

    Klyce, Stephen D.; Wilson, Steven E.

    1989-12-01

    The cornea is the major refractive element in the eye; even minor surface distortions can produce a significant reduction in visual acuity. Standard clinical methods used to evaluate corneal shape include keratometry, which assumes the cornea is ellipsoidal in shape, and photokeratoscopy, which images a series of concentric light rings on the corneal surface. These methods fail to document many of the corneal distortions that can degrade visual acuity. Algorithms have been developed to reconstruct the three dimensional shape of the cornea from keratoscope images, and to present these data in the clinically useful display of color-coded contour maps of corneal surface power. This approach has been implemented on a new generation video keratoscope system (Computed Anatomy, Inc.) with rapid automatic digitization of the image rings by a rule-based approach. The system has found clinical use in the early diagnosis of corneal shape anomalies such as keratoconus and contact lens-induced corneal warpage, in the evaluation of cataract and corneal transplant procedures, and in the assessment of corneal refractive surgical procedures. Currently, ray tracing techniques are being used to correlate corneal surface topography with potential visual acuity in an effort to more fully understand the tolerances of corneal shape consistent with good vision and to help determine the site of dysfunction in the visually impaired.

  13. Turning the tide of corneal blindness.

    PubMed

    Oliva, Matthew S; Schottman, Tim; Gulati, Manoj

    2012-01-01

    Corneal diseases represent the second leading cause of blindness in most developing world countries. Worldwide, major investments in public health infrastructure and primary eye care services have built a strong foundation for preventing future corneal blindness. However, there are an estimated 4.9 million bilaterally corneal blind persons worldwide who could potentially have their sight restored through corneal transplantation. Traditionally, barriers to increased corneal transplantation have been daunting, with limited tissue availability and lack of trained corneal surgeons making widespread keratoplasty services cost prohibitive and logistically unfeasible. The ascendancy of cataract surgical rates and more robust eye care infrastructure of several Asian and African countries now provide a solid base from which to dramatically expand corneal transplantation rates. India emerges as a clear global priority as it has the world's largest corneal blind population and strong infrastructural readiness to rapidly scale its keratoplasty numbers. Technological modernization of the eye bank infrastructure must follow suit. Two key factors are the development of professional eye bank managers and the establishment of Hospital Cornea Recovery Programs. Recent adaptation of these modern eye banking models in India have led to corresponding high growth rates in the procurement of transplantable tissues, improved utilization rates, operating efficiency realization, and increased financial sustainability. The widespread adaptation of lamellar keratoplasty techniques also holds promise to improve corneal transplant success rates. The global ophthalmic community is now poised to scale up widespread access to corneal transplantation to meet the needs of the millions who are currently blind. PMID:22944753

  14. Tyrosinemia produced by 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione (NTBC) in experimental animals and its relationship to corneal injury

    SciTech Connect

    Lock, Edward A. . E-mail: e.lock@ljmu.ac.uk; Gaskin, Peter; Ellis, Martin; Provan, William M.; Smith, Lewis L.

    2006-08-15

    2-(2-Nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione (NTBC) is a potent inhibitor of rat liver 4-hydroxyphenylpyruvate dioxygenase (HPPD) leading to tyrosinemia and corneal opacity. We examined the effect of NTBC on the extent of tyrosinemia and production of corneal lesions in the beagle dog, rabbit and rhesus monkey, as part of safety evaluation on this drug. A single oral dose of 10 mg NTBC/kg to beagle dogs or rabbits increased the concentration of tyrosine in plasma and aqueous humour of the eye, the tyrosinemia being both time- and dose-dependent. Hepatic HPPD was markedly inhibited with little effect on the activity of tyrosine aminotransferase (TAT) and homogentisic acid oxidase at the time of peak plasma tyrosine. Daily oral administration of NTBC to beagle dogs at 0.1, 0.5, 1.5 and 5 mg/kg/day produced corneal opacities with an incidence of 34% following 11 weeks of dosing, which reversed upon withdrawal of the drug. Tyrosine in plasma and aqueous humour was increased at all dose levels, 18 weeks after dosing. In contrast, daily oral administration of NTBC to rabbits for 6 weeks and rhesus monkeys for 12 weeks at 10 mg/kg/day produced no evidence of corneal opacities although tyrosine values were markedly increased. Our studies have shown that NTBC is a potent inhibitor of rabbit, beagle dog and by inference rhesus monkey liver HPPD producing a marked tyrosinemia in all species studied, while only beagle dogs show corneal lesions. The production of corneal lesions in experimental animals exposed to NTBC does not appear to be simply related to the concentration of tyrosine in ocular fluid, other as yet unidentified factors appear to be necessary to trigger tissue injury.

  15. EGF and PGE2: effects on corneal endothelial cell migration and monolayer spreading during wound repair in vitro.

    PubMed

    Joyce, N C; Joyce, S J; Powell, S M; Meklir, B

    1995-07-01

    In vivo repair of the adult human corneal endothelium occurs mainly by movement of cells into the wound defect rather than by cell division. Two forms of cell movement contribute to endothelial wound repair: migration of individual cells into the defect and spreading of the confluent monolayer into the wound area. This laboratory has developed a tissue culture model using rabbit corneal endothelial cells pretreated with the mitotic inhibitor 5-fluorouracil to mimic the relatively amitotic state of human corneal endothelium in vivo. This model permits study of the effects of growth factors and other agents on individual cell migration and monolayer spreading in response to wounding. mRNA for epidermal growth factor (EGF) and its receptor has been detected in cultured corneal endothelial cells and EGF receptors have been detected on human corneal endothelial cells in situ, suggesting that this growth factor may act in an autocrine manner. Prostaglandin E2 (PGE2) is synthesized by cultured corneal endothelial cells and is present in relatively high quantity in aqueous humor in response to corneal wounding and to inflammation in the anterior chamber. Although corneal endothelial cells may be exposed to both EGF and PGE2, little is known about their effects on monolayer repair. The current study compared the effects of PGE2 alone, EGF alone, and both agents in combination on individual cell migration and monolayer spreading using the wound model system and also determined the effect of EGF on PGE2 secretion using a commercial immunoassay. A 15 min exposure of wounded cultures to exogenous PGE2 stimulated individual cell migration and suppressed monolayer spreading.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7587307

  16. Long-Term Observation of Coexistence of Posterior Polymorphous Corneal Dystrophy, Resultant High Myopia and Nonkeratoconic Developing Corneal Astigmatism: A Case Report of 7-Year Tracking in a Chinese Boy.

    PubMed

    Shen, Jianqin; Chixin, Du; Gu, Yangshun

    2015-06-01

    Posterior polymorphous corneal dystrophy (PPCD) is an extremely rare, bilateral, and inherited disorder, which affects the corneal endothelium and Descemet's membrane. Few PPCD cases in Chinese patients have been published so far. As far as we know, there are few studies which focused on the associations between PPCD and high myopia either. Here we report a rare case of coexistence of posterior polymorphous corneal dystrophy, resultant high myopia and with-the-rule developing corneal astigmatism in a young Chinese boy. A 6-year-old boy was first referred to our department 7 years ago, complaining of bilateral poor vision. Examinations of both eyes including ophthalmologic examination, cycloplegic refraction examination, confocal microscopy findings, and corneal topography were performed. Bilateral small aggregates of vesicular lesions and patchy hyperreflectivity were observed at the level of the Descemet's membrane on confocal microscopy, which is consistent with typical PPCD. Optometry and corneal topography examinations showed a resultant high myopia. Ocular examinations were performed annually to follow up with the patient in the past 7 years. The corneal lesions remained stable whereas an axial elongation and a sharp increase in both spherical and cylindrical equivalent power were observed. Close follow-ups including thorough scrutiny of the endothelium and systematic ocular ancillary examinations are essential for patients with PPCD. The pathological coexistence of PPCD and high myopia in our case is possibly due to a shared etiological pathway or genetic background. Advanced genetic analysis on similar cases is expected if more samples can be provided. PMID:26061314

  17. Decellularization of human stromal refractive lenticules for corneal tissue engineering

    PubMed Central

    Yam, Gary Hin-Fai; Yusoff, Nur Zahirah Binte M.; Goh, Tze-Wei; Setiawan, Melina; Lee, Xiao-Wen; Liu, Yu-Chi; Mehta, Jodhbir S.

    2016-01-01

    Small incision lenticule extraction (SMILE) becomes a procedure to correct myopia. The extracted lenticule can be used for other clinical scenarios. To prepare for allogeneic implantation, lenticule decellularization with preserved optical property, stromal architecture and chemistry would be necessary. We evaluated different methods to decellularize thin human corneal stromal lenticules created by femtosecond laser. Treatment with 0.1% sodium dodecylsulfate (SDS) followed by extensive washes was the most efficient protocol to remove cellular and nuclear materials. Empty cell space was found inside the stroma, which displayed aligned collagen fibril architecture similar to native stroma. The SDS-based method was superior to other treatments with hyperosmotic 1.5 M sodium chloride, 0.1% Triton X-100 and nucleases (from 2 to 10 U/ml DNase and RNase) in preserving extracellular matrix content (collagens, glycoproteins and glycosaminoglycans). The stromal transparency and light transmittance was indifferent to untreated lenticules. In vitro recellularization showed that the SDS-treated lenticules supported corneal stromal fibroblast growth. In vivo re-implantation into a rabbit stromal pocket further revealed the safety and biocompatibility of SDS-decellularized lenticules without short- and long-term rejection risk. Our results concluded that femtosecond laser-derived human stromal lenticules decellularized by 0.1% SDS could generate a transplantable bioscaffold with native-like stromal architecture and chemistry. PMID:27210519

  18. Essential ions for maintenance of the corneal epithelial surface.

    PubMed

    Bachman, W G; Wilson, G

    1985-11-01

    It is generally believed that tears are required to furnish only oxygen to the corneal epithelium. However, as tears are a very complicated solution, it is likely that other factors are essential to the cells of the corneal surface. The amount of light scattered from the epithelial surface of the excised rabbit cornea was examined with the in vitro specular microscope while the epithelium was bathed in different solutions. It was shown that the epithelial surface was maintained best with a buffered solution containing potassium, calcium, magnesium, phosphate and bicarbonate, in addition to sodium chloride. The solution was named Basic Tear Solution (BTS). The effect was not due to osmolarity. Potassium was particularly important, as corneas bathed with sodium chloride and potassium chloride were maintained better than corneas bathed with sodium chloride only. The appearance of the epithelial surface was different in these bathing solutions. In sodium chloride the surface scattered more light and more cells were sloughed. Least light was scattered in BTS, and cell-sloughing was at a minimum. Thus, the rate at which cells were sloughed from the epithelial surface and the quality of the surface were dependent on the bathing solution. PMID:2414247

  19. Decellularization of human stromal refractive lenticules for corneal tissue engineering.

    PubMed

    Yam, Gary Hin-Fai; Yusoff, Nur Zahirah Binte M; Goh, Tze-Wei; Setiawan, Melina; Lee, Xiao-Wen; Liu, Yu-Chi; Mehta, Jodhbir S

    2016-01-01

    Small incision lenticule extraction (SMILE) becomes a procedure to correct myopia. The extracted lenticule can be used for other clinical scenarios. To prepare for allogeneic implantation, lenticule decellularization with preserved optical property, stromal architecture and chemistry would be necessary. We evaluated different methods to decellularize thin human corneal stromal lenticules created by femtosecond laser. Treatment with 0.1% sodium dodecylsulfate (SDS) followed by extensive washes was the most efficient protocol to remove cellular and nuclear materials. Empty cell space was found inside the stroma, which displayed aligned collagen fibril architecture similar to native stroma. The SDS-based method was superior to other treatments with hyperosmotic 1.5 M sodium chloride, 0.1% Triton X-100 and nucleases (from 2 to 10 U/ml DNase and RNase) in preserving extracellular matrix content (collagens, glycoproteins and glycosaminoglycans). The stromal transparency and light transmittance was indifferent to untreated lenticules. In vitro recellularization showed that the SDS-treated lenticules supported corneal stromal fibroblast growth. In vivo re-implantation into a rabbit stromal pocket further revealed the safety and biocompatibility of SDS-decellularized lenticules without short- and long-term rejection risk. Our results concluded that femtosecond laser-derived human stromal lenticules decellularized by 0.1% SDS could generate a transplantable bioscaffold with native-like stromal architecture and chemistry. PMID:27210519

  20. Regenerative Cell Therapy for Corneal Endothelium.

    PubMed

    Bartakova, Alena; Kunzevitzky, Noelia J; Goldberg, Jeffrey L

    2014-09-01

    Endothelial cell dysfunction as in Fuchs dystrophy or pseudophakic bullous keratopathy, and the limited regenerative capacity of human corneal endothelial cells (HCECs), drive the need for corneal transplant. In response to limited donor corneal availability, significant effort has been directed towards cell therapy as an alternative to surgery. Stimulation of endogenous progenitors, or transplant of stem cell-derived HCECs or in vitro-expanded, donor-derived HCECs could replace traditional surgery with regenerative therapy. Ex vivo expansion of HCECs is technically challenging, and the basis for molecular identification of functional HCECs is not established. Delivery of cells to the inner layer of the human cornea is another challenge: different techniques, from simple injection to artificial corneal scaffolds, are being investigated. Despite remaining questions, corneal endothelial cell therapies, translated to the clinic, represent the future for the treatment of corneal endotheliopathies. PMID:25328857

  1. [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). PMID:27562284

  2. Carbon tetrachloride-induced liver injury in the rabbit.

    PubMed Central

    Bernacchi, A. S.; de Castro, C. R.; de Ferreyra, E. C.; Villarruel, M. C.; Fernández, G.; de Fenos, O. M.; Castro, J. A.

    1983-01-01

    CCl4 administration to rabbits leads to early destruction of liver microsomal cytochrome P-450, to depression of glucose 6 phosphatase, to ultrastructurally revealable alterations and to an intense necrosis and fat accumulation in liver. Despite the known resistance of rabbit liver microsomes to lipid peroxidation, CCl4 administration to rabbits promoted lipid peroxidation of their liver microsomal lipids as revealable by the diene hyperconjugation technique, at periods of time from 1 to 12 h. Nevertheless, the intensity of this process is not equivalent to that occurring in rat liver microsomes, since the arachidonic acid content of rabbit liver microsomal lipids does not decrease at either 6 or 24 h after CCl4 administration. Rabbit liver is able to activate CCl4 to reactive metabolites that bind covalently to lipids. Relevance of covalent binding of CCl4 reactive metabolites and CCl4-promoted lipid peroxidation to CCl4-induced rabbit liver injury is analysed. Images Fig. 1 Fig. 2 PMID:6309207

  3. Surgical technique: coupling of intrastromal corneal ring segments for ectatic corneal disorders in eye bank corneas

    PubMed Central

    Moshirfar, Majid; Hsu, Maylon; Khalifa, Yousuf M

    2011-01-01

    The management of corneal ectasia is evolving, with intrastromal corneal ring segments playing an important role in delaying or eliminating the need for penetrating keratoplasty. This paper describes a modification in the implantation technique of intrastromal corneal ring segments that allows for coupling of the two segments with suture, affording more structural support. PMID:22034567

  4. Primary corneal melanocytoma in a Collie.

    PubMed

    Bauer, Bianca; Leis, Marina L; Sayi, Soraya

    2015-09-01

    A 6-year-old female, spayed Collie was referred to the Western College of Veterinary Medicine for a 12-month history of a progressive right corneal mass. A superficial keratectomy was performed and histopathology revealed a corneal melanocytoma with complete excision. There has been no recurrence of the neoplasm to date (12 months). This is the first known report of an isolated corneal melanocytoma in a canine. PMID:25296627

  5. Viral infections of rabbits.

    PubMed

    Kerr, Peter J; Donnelly, Thomas M

    2013-05-01

    Viral diseases of rabbits have been used historically to study oncogenesis (e.g. rabbit fibroma virus, cottontail rabbit papillomavirus) and biologically to control feral rabbit populations (e.g. myxoma virus). However, clinicians seeing pet rabbits in North America infrequently encounter viral diseases although myxomatosis may be seen occasionally. The situation is different in Europe and Australia, where myxomatosis and rabbit hemorrhagic disease are endemic. Advances in epidemiology and virology have led to detection of other lapine viruses that are now recognized as agents of emerging infectious diseases. Rabbit caliciviruses, related to rabbit hemorrhagic disease, are generally avirulent, but lethal variants are being identified in Europe and North America. Enteric viruses including lapine rotavirus, rabbit enteric coronavirus and rabbit astrovirus are being acknowledged as contributors to the multifactorial enteritis complex of juvenile rabbits. Three avirulent leporid herpesviruses are found in domestic rabbits. A fourth highly pathogenic virus designated leporid herpesvirus 4 has been described in Canada and Alaska. This review considers viruses affecting rabbits by their clinical significance. Viruses of major and minor clinical significance are described, and viruses of laboratory significance are mentioned. PMID:23642871

  6. Effect of Intraoperative Corneal Stromal Pocket Irrigation in Small Incision Lenticule Extraction

    PubMed Central

    Liu, Yu-Chi; Jayasinghe, Lasitha; Ang, Heng Pei; Lwin, Nyein Chan; Yam, Gary Hin Fai; Mehta, Jodhbir S.

    2015-01-01

    This study aimed at evaluating the effect of intraoperative corneal pocket irrigation in small incision lenticule extraction (SMILE) and compares it to that in femtosecond laser-assisted in situ keratomileusis (FS-LASIK). Sixteen rabbit eyes underwent a SMILE procedure, with 8 eyes having corneal pocket irrigation, while the other 8 eyes were without irrigation. Another 16 eyes underwent a FS-LASIK procedure for comparison, with 8 eyes having flap irrigation, while the other 8 eyes were without irrigation. The results showed that the changes in the total corneal thickness, anterior and posterior lamellar thickness, measured by the anterior segment optical coherence tomography, were comparable between the SMILE with and without irrigation groups, suggesting that the irrigation did not lead to significant changes in the corneal thickness. However, at postoperative 8 hours, in vivo confocal microscopy showed that the interface reflectivity in the SMILE with irrigation group was significantly higher than that in other three groups. The presence of interface fluid was further confirmed by the identification of fluid pockets with undulated collagen shown on histological section in the post-SMILE with irrigation eyes. Our findings might contribute to the occurrence of post-SMILE delayed immediate visual quality recovery and further clinical study is required. PMID:26273659

  7. Effect of Intraoperative Corneal Stromal Pocket Irrigation in Small Incision Lenticule Extraction.

    PubMed

    Liu, Yu-Chi; Jayasinghe, Lasitha; Ang, Heng Pei; Lwin, Nyein Chan; Yam, Gary Hin Fai; Mehta, Jodhbir S

    2015-01-01

    This study aimed at evaluating the effect of intraoperative corneal pocket irrigation in small incision lenticule extraction (SMILE) and compares it to that in femtosecond laser-assisted in situ keratomileusis (FS-LASIK). Sixteen rabbit eyes underwent a SMILE procedure, with 8 eyes having corneal pocket irrigation, while the other 8 eyes were without irrigation. Another 16 eyes underwent a FS-LASIK procedure for comparison, with 8 eyes having flap irrigation, while the other 8 eyes were without irrigation. The results showed that the changes in the total corneal thickness, anterior and posterior lamellar thickness, measured by the anterior segment optical coherence tomography, were comparable between the SMILE with and without irrigation groups, suggesting that the irrigation did not lead to significant changes in the corneal thickness. However, at postoperative 8 hours, in vivo confocal microscopy showed that the interface reflectivity in the SMILE with irrigation group was significantly higher than that in other three groups. The presence of interface fluid was further confirmed by the identification of fluid pockets with undulated collagen shown on histological section in the post-SMILE with irrigation eyes. Our findings might contribute to the occurrence of post-SMILE delayed immediate visual quality recovery and further clinical study is required. PMID:26273659

  8. System for tracking transplanted limbal epithelial stem cells in the treatment of corneal stem cell deficiency

    NASA Astrophysics Data System (ADS)

    Boadi, J.; Sangwal, V.; MacNeil, S.; Matcher, S. J.

    2015-03-01

    The prevailing hypothesis for the existence and healing of the avascular corneal epithelium is that this layer of cells is continually produced by stem cells in the limbus and transported onto the cornea to mature into corneal epithelium. Limbal Stem Cell Deficiency (LSCD), in which the stem cell population is depleted, can lead to blindness. LSCD can be caused by chemical and thermal burns to the eye. A popular treatment, especially in emerging economies such as India, is the transplantation of limbal stem cells onto damaged limbus with hope of repopulating the region. Hence regenerating the corneal epithelium. In order to gain insights into the success rates of this treatment, new imaging technologies are needed in order to track the transplanted cells. Optical Coherence Tomography (OCT) is well known for its high resolution in vivo images of the retina. A custom OCT system has been built to image the corneal surface, to investigate the fate of transplanted limbal stem cells. We evaluate two methods to label and track transplanted cells: melanin labelling and magneto-labelling. To evaluate melanin labelling, stem cells are loaded with melanin and then transplanted onto a rabbit cornea denuded of its epithelium. The melanin displays strongly enhanced backscatter relative to normal cells. To evaluate magneto-labelling the stem cells are loaded with magnetic nanoparticles (20-30nm in size) and then imaged with a custom-built, magneto-motive OCT system.

  9. An Ultra-thin Amniotic Membrane as Carrier in Corneal Epithelium Tissue-Engineering

    PubMed Central

    Zhang, Liying; Zou, Dulei; Li, Sanming; Wang, Junqi; Qu, Yangluowa; Ou, Shangkun; Jia, Changkai; Li, Juan; He, Hui; Liu, Tingting; Yang, Jie; Chen, Yongxiong; Liu, Zuguo; Li, Wei

    2016-01-01

    Amniotic membranes (AMs) are widely used as a corneal epithelial tissue carrier in reconstruction surgery. However, the engineered tissue transparency is low due to the translucent thick underlying AM stroma. To overcome this drawback, we developed an ultra-thin AM (UAM) by using collagenase IV to strip away from the epithelial denuded AM (DAM) some of the stroma. By thinning the stroma to about 30 μm, its moist and dry forms were rendered acellular, optically clear and its collagen framework became compacted and inerratic. Engineered rabbit corneal epithelial cell (RCEC) sheets generated through expansion of limbal epithelial cells on UAM were more transparent and thicker than those expanded on DAM. Moreover, ΔNp63 and ABCG2 gene expression was greater in tissue engineered cell sheets expanded on UAM than on DAM. Furthermore, 2 weeks after surgery, the cornea grafted with UAM based cell sheets showed higher transparency and more stratified epithelium than the cornea grafted with DAM based cell sheets. Taken together, tissue engineered corneal epithelium generated on UAM has a preferable outcome because the transplanted tissue is more transparent and better resembles the phenotype of the native tissue than that obtained by using DAM for this procedure. UAM preserves compact layer of the amniotic membrane and maybe an ideal substrate for corneal epithelial tissue engineering. PMID:26876685

  10. Ultraprecise medical applications with ultrafast lasers: corneal surgery with femtosecond lasers

    NASA Astrophysics Data System (ADS)

    Loesel, Frieder H.; Kurtz, Ron M.; Horvath, Christopher; Sayegh, Samir I.; Mourou, Gerard A.; Bille, Josef F.; Juhasz, Tibor

    1999-02-01

    We investigated refractive corneal surgery in vivo and in vitro by intrastromal photodisruption using a compact ultrafast femtosecond laser system. Ultrashort-pulsed lasers operating in the femtosecond time regime are associated with significantly smaller and deterministic threshold energies for photodisruption, as well as reduced shock waves and smaller cavitation bubbles than the nanosecond or picosecond lasers. Our reliable all-solid-state laser system was specifically designed for real world medical applications. By scanning the 5 micron focus spot of the laser below the corneal surface, the overlapping small ablation volumes of single pulses resulted in contiguous tissue cutting and vaporization. Pulse energies were typically in the order of a few microjoules. Combination of different scanning patterns enabled us to perform corneal flap cutting, femtosecond-LASIK, and femtosecond intrastromal keratectomy in porcine, rabbit, and primate eyes. The cuts proved to be highly precise and possessed superior dissection and surface quality. Preliminary studies show consistent refractive changes in the in vivo studies. We conclude that the technology is capable to perform a variety of corneal refractive procedures at high precision, offering advantages over current mechanical and laser devices and enabling entirely new approaches for refractive surgery.

  11. Development and Effects of FTY720 Ophthalmic Solution on Corneal Allograft Survival

    PubMed Central

    Liu, Zhaochuan; Lin, Haotian; Huang, Chulong; Chen, Wan; Xiang, Wu; Geng, Yu; Chen, Weirong

    2015-01-01

    Fingolimod (FTY720), a novel class of sphingosine 1-phosphate receptor modulators, has received special interest among ophthalmologists, particularly given that oral administration of FTY720 has proven to effectively treat corneal graft rejection in animal models. However, no studies have examined the performance of FTY720 as an ophthalmic solution in reducing corneal rejection in high-risk corneal rejection models, and the stability and ocular irritation profile of FTY720 ophthalmic solution are also unknown. Thus, we developed 0.1%, 0.2% and 0.5% FTY720 ophthalmic solutions and evaluated their chemical stabilities under various storage conditions with high- performance liquid chromatography. To investigate the ocular irritancy of the FTY720 ophthalmic solution, New Zealand albino rabbits were subjected to the Draize test. Furthermore, classic, well-established rat allogenic penetrating keratoplasty models were used to investigate the anti-rejection efficacy of the tested FTY720 ophthalmic solutions. We found that the non-irritating 0.5% FTY720 ophthalmic solution could prolong corneal allograft survival in rats with significant efficacy for about one month. Furthermore, no significant concentration changes occurred in any of the types of FTY720 ophthalmic solutions within three months. These results revealed crucial profiles of FTY720 ophthalmic solutions and warrant further investigation and optimization of FTY720 in the anti-rejection therapy after keratoplasty. PMID:26558849

  12. Keratorefractive Effect of High Intensity Focused Ultrasound Keratoplasty on Rabbit Eyes

    PubMed Central

    Du, Zhiyu; Zhang, Dan; Zhang, Yu

    2016-01-01

    Purpose. To evaluate high intensity focused ultrasound (HIFU) as an innovation and noninvasive technique to correct presbyopia by altering corneal curvature in the rabbit eye. Methods. Eighteen enucleated rabbit eyes were treated with a prototype HIFU keratoplasty. According to the therapy power, these eyes were divided three groups: group 1 (1 W), group 2 (2 W), and group 3 (3 W). The change in corneal power was quantified by a Sirius Scheimpflug camera. Light microscopy (LM) and transmission electron microscopy (TEM) were performed to determine the effect on the corneal stroma. Results. In the treated eyes, the corneal curvature increases from 49.42 ± 0.30 diopters (D) and 48.00 ± 1.95 D before procedure to 51.37 ± 1.11 D and 57.00 ± 1.84 D after HIFU keratoplasty application in groups 1 and 3, respectively. The major axis and minor axis of the focal region got longer when the powers of the HIFU got increased; the difference was statistically significant (p < 0.05). LM and TEM showed HIFU-induced shrinkage of corneal stromal collagen with little disturbance to the underlying epithelium. Conclusions. We have preliminarily exploited HIFU to establish a new technique for correcting presbyopia. HIFU keratoplasty will be a good application prospect for treating presbyopia. PMID:27382486

  13. Central Corneal Thickness in Children

    PubMed Central

    2011-01-01

    Objective To report the central corneal thickness (CCT) in healthy white, African-American, and Hispanic children from birth to 17 years of age. Design Prospective observational multicenter study. Central corneal thickness was measured with a hand-held contact pachymeter. Results Two thousand seventy-nine children were included in the study, with ages ranging from day of birth to 17 years. Included were 807 white, 494 Hispanic, and 474 African-American individuals, in addition to Asian, unknown and mixed race individuals. African-American children had thinner corneas on average than that of both white (p< .001) and Hispanic children (p< .001) by approximately 20 micrometers. Thicker median CCT was observed with each successive year of age from age 1 to 11 years, with year-to-year differences steadily decreasing and reaching a plateau after age 11 at 573 micrometers in white and Hispanic children and 551 micrometers in African-American children. For every 100 micrometers of thicker CCT measured, the intraocular pressure was 1.5 mmHg higher on average (p< 0.001). For every diopter of increased myopic refractive error (p< 0.001) CCT was 1 micrometer thinner on average. Conclusions Median CCT increases with age from 1 to 11 years with the greatest increase present in the youngest age groups. African-American children on average have thinner central corneas than white and Hispanic children, while white and Hispanic children demonstrate similar central corneal thickness. PMID:21911662

  14. Corneal Swelling with Cosmetic etafilcon A Lenses versus No Lens Wear

    PubMed Central

    Moezzi, Amir M.; Varikooty, Jalaiah; Schulze, Marc; Ngo, William; Lorenz, Kathrine Osborn; Boree, Danielle; Jones, Lyndon W.

    2016-01-01

    ABSTRACT Purpose To determine if the use of pigments or adding polyvinyl pyrrolidone during the fabrication of 1-DAY ACUVUE DEFINE (AD) brand contact lenses impacts open-eye corneal swelling compared with no lens wear (NLW). Methods A partial double-masked, randomized, bilateral crossover study was conducted in 24 Asian subjects using AD, 1-DAY ACUVUE DEFINE with Lacreon (ADL), NLW, and a control lens with no tint (1-DAY ACUVUE MOIST [AM]). Central corneal thickness was measured before insertion and immediately after removal after 8 ± 1 h of open-eye wear using an optical pachymeter in one eye. Corneal thickness along a 10-mm cord was measured in the contralateral eye using the Visante optical coherence tomographer (OCT). Corneal swelling was tested for noninferiority using a 5% margin. The endothelial bleb response was measured at baseline and 20 min after lens insertion using specular microscopy. Subjective grading of corneal staining and limbal/bulbar hyperemia were also monitored. Results After 8 ± 1 h of open-eye wear, central corneal swelling across the study lenses with either optical pachymeter or OCT methods was negligible. Peripheral corneal swelling least-square mean differences with OCT were −0.03% (95% confidence interval [95% CI], −0.65 to 0.58%) and −0.26% (95% CI, −0.87 to 0.36%) between AD and ADL and the control lens (AM), respectively, and 1.67% (95% CI, 1.06 to 2.29%) and 1.45% (95% CI, 0.84 to 2.06%) between AD and ADL and NLW, respectively. No endothelial blebs were observed. No clinically significant differences were distinguished between the lenses and NLW for corneal staining and limbal/bulbar hyperemia. Conclusions After 8 ± 1 h of open-eye wear, central and peripheral corneal swelling along the horizontal meridian with AD, ADL, AM, and NLW were equivalent. These results confirm that the addition of polyvinyl pyrrolidone or pigments to etafilcon A to obtain a limbal ring design have no impact on corneal swelling or limbal

  15. [Morphological and functional studies on nerve regeneration after corneal nerve injuries].

    PubMed

    Zhang, Z Q; Xie, L X; Dong, X G

    1994-07-01

    Using gold chloride impregnation of nerves and horse-radish peroxidase (HRP) axoplasma retrograde tracing technique, we monitored nerve regeneration over a period of 6 months following penetrating perilimbal incisions and penetrating keratoplasties (PKP) in rabbits. Post-operatively, at 1 month after a 180 degrees perilimbal incision, loose unconnected subepithelial plexus were present in the limbus, at 2 months 1-2 bundles of deep stromal nerve were seen in the stroma and by 6 months only a few stromal nerves regenerated. There was no difference in nerve regeneration between post-operative autograft and allograft PKP. By 6 months, the quantity of HRP-labelled cells in the trigeminal ganglia was less than the normal level. The results indicated that nerve regeneration by 6 months after corneal nerve injuries was inadequate to restore a normal corneal nerve extent and function. PMID:7843026

  16. A simple and non-contact optical imaging probe for evaluation of corneal diseases

    NASA Astrophysics Data System (ADS)

    Hong, Xun Jie Jeesmond; Shinoj, V. K.; Murukeshan, V. M.; Baskaran, M.; Aung, T.

    2015-09-01

    Non-contact imaging techniques are preferred in ophthalmology. Corneal disease is one of the leading causes of blindness worldwide, and a possible way of detection is by analyzing the shape and optical quality of the cornea. Here, a simple and cost-effective, non-contact optical probe system is proposed and illustrated. The probe possesses high spatial resolutions and is non-dependent on coupling medium, which are significant for a clinician and patient friendly investigation. These parameters are crucial, when considering an imaging system for the objective diagnosis and management of corneal diseases. The imaging of the cornea is performed on ex vivo porcine samples and subsequently on small laboratory animals, in vivo. The clinical significance of the proposed study is validated by performing imaging of the New Zealand white rabbit's cornea infected with Pseudomonas.

  17. The role of free radicals in paraquat-induced corneal lesions.

    PubMed

    Nordquist, R E; Nguyen, H; Poyer, J L; Carubelli, R

    1995-07-01

    Paraquat is a synthetic bipyridylium salt widely used as herbicide and defoliant. Enzyme-catalyzed redoxcycling of paraquat generates oxygen radicals. The toxic, even lethal, effects of paraquat are due to free radical-mediated tissue injury. Ocular lesions, sometimes quite severe, have been observed following accidental splashing of paraquat solutions onto the eyes. These studies were designed to document the generation of paraquat free radicals in corneal tissue, and to describe the histological nature of the corneal injuries in experimental animals (rabbits and monkeys). The EPR spectrum of rabbit corneas, 30 min. after intrastromal injection of paraquat, showed the signal of the free radical of paraquat. Ultrastructural studies of corneas 8 days after intrastromal injections (100 microliters) of paraquat solutions showed that the initial lesions occur at the epithelium/basement membrane interface. In rabbit cornea, dose dependent lesions were observed, i.e. whereas 50 mM paraquat caused only minimal damage to the epithelial basement membrane, 75 mM caused complete dissolution to the basement membrane with some damage to stromal collagen, and loss of epithelium with stromal ulceration and severe inflammatory response were observed with 150 mM paraquat. Monkey corneas were less susceptible than those of rabbits to the effects of paraquat. No lesions were observed following intrastromal injections of 50 mM or 75 mM paraquat. With higher concentrations of paraquat (100 mM and 150 mM) the primary injuries were to the proximal and lateral plasma membranes of basal epithelial cells; basement membrane alterations were detected only adjacent to areas of significant plasma membrane damage. The underlying Bowman's membrane and stroma were not affected. Anatomical differences between the corneas of rabbit and monkeys as well as possible biochemical differences may account for the species differences observed. PMID:7647920

  18. Modeling the rabbit's eye with the Mueller matrix for birefringent properties

    NASA Astrophysics Data System (ADS)

    Baba, Justin S.; Cooper, Califf T.; Cote, Gerard L.

    2003-07-01

    The effect of changing corneal birefringence, due to motion artifact, remains a major obstacle to the development of an accurate non-invasive polarimetric glucose sensor for patients with diabetes mellitus. Consequently, there is still a need to characterize fully, and to quantify the relative changes in corneal birefringence to facilitate the optimization of detection algorithms, enabling in vivo accuracy within 10mg/dl. In this paper, we present preliminary results, utilizing a Mueller matrix imaging technique, that demonstrates notable relative changes in the apparent retardance and in the apparent fast axis location of rabbit cornea.

  19. Novel Technique of Transepithelial Corneal Cross-Linking Using Iontophoresis in Progressive Keratoconus.

    PubMed

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

    2016-01-01

    In this work, the authors presented the techniques and the preliminary results at 6 months of a randomized controlled trial (NCT02117999) comparing a novel transepithelial corneal cross-linking protocol using iontophoresis with the Dresden protocol for the treatment of progressive keratoconus. At 6 months, there was a significant average improvement with an average flattening of the maximum simulated keratometry reading of 0.72 ± 1.20 D (P = 0.01); in addition, corrected distance visual acuity improved significantly (P = 0.08) and spherical equivalent refraction was significantly less myopic (P = 0.02) 6 months after transepithelial corneal cross-linking with iontophoresis. The novel protocol using iontophoresis showed comparable results with standard corneal cross-linking to halt progression of keratoconus during 6-month follow-up. Investigation of the long-term RCT outcomes are ongoing to verify the efficacy of this transepithelial corneal cross-linking protocol and to determine if it may be comparable with standard corneal cross-linking in the management of progressive keratoconus. PMID:27597895

  20. Novel Technique of Transepithelial Corneal Cross-Linking Using Iontophoresis in Progressive Keratoconus

    PubMed Central

    Raffa, Paolo; Rosati, Marianna

    2016-01-01

    In this work, the authors presented the techniques and the preliminary results at 6 months of a randomized controlled trial (NCT02117999) comparing a novel transepithelial corneal cross-linking protocol using iontophoresis with the Dresden protocol for the treatment of progressive keratoconus. At 6 months, there was a significant average improvement with an average flattening of the maximum simulated keratometry reading of 0.72 ± 1.20 D (P = 0.01); in addition, corrected distance visual acuity improved significantly (P = 0.08) and spherical equivalent refraction was significantly less myopic (P = 0.02) 6 months after transepithelial corneal cross-linking with iontophoresis. The novel protocol using iontophoresis showed comparable results with standard corneal cross-linking to halt progression of keratoconus during 6-month follow-up. Investigation of the long-term RCT outcomes are ongoing to verify the efficacy of this transepithelial corneal cross-linking protocol and to determine if it may be comparable with standard corneal cross-linking in the management of progressive keratoconus. PMID:27597895

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

    PubMed Central

    ZHENG, WENJING; MA, MINGMING; DU, ERGANG; ZHANG, ZHENGWEI; JIANG, KELIMU; GU, QING; KE, BILIAN

    2015-01-01

    The aim of the present study was to investigate the therapeutic efficacy of fibroblast growth factor 10 (FGF10) in the promotion of healing, survival and expression of mucin in corneal epithelial cells in a rabbit dry eye model. A total of 12 healthy female New Zealand white rabbits were divided randomly into three groups. The lacrimal glands were injected with saline either alone (normal control group) or with concanavalin A (Con A), with either topical phosphate-buffered saline (PBS; PBS control group) or 25 µg/ml FGF10 (FGF10 treatment group). Lacrimal gland inflammation, tear function, corneal epithelial cell integrity, cell apoptosis and mucin expression were subsequently assessed. Lacrimal gland tissue biopsies were performed in conjunction with histology and electron microscopy observations. Tear meniscus height (TMH) and tear meniscus area (TMA) were measured using Fourier domain-optical coherence tomography. Tear membrane break-up time (TBUT) was also assessed and corneal fluorescein staining was performed. The percentages of apoptotic corneal and conjunctival (Cj) epithelial cells (ECs) were counted using a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method. The mRNA expression levels of Muc1 were determined using reverse transcription-quantitative polymerase chain reaction analyses. The TMH and TMA values of the PBS and treatment groups were found to be significantly reduced, compared with those of the normal control group 3 days after Con A injection. However, the TMH and TMA of the FGF10 treatment group were higher, compared with those of the PBS group 3 and 7 days after treatment, respectively. Furthermore, the FGF10 treatment group exhibited prolonged TBUT, reduced corneal fluorescein staining and repaired epithelial cell ultra-structure7 days after treatment. The percentages of apoptotic corneal- and Cj-ECs in the FGF10 treatment group were significantly reduced, compared with those in the PBS group. FGF10 significantly

  2. Small incision lenticule extraction (SMILE) and femtosecond laser LASIK: comparison of corneal wound healing and inflammation

    PubMed Central

    Dong, Zixian; Zhou, Xingtao; Wu, Jihong; Zhang, Zhehuan; Li, Tao; Zhou, Zimei; Zhang, Shenghai; Li, Gang

    2014-01-01

    Aim To evaluate and compare early corneal wound healing and inflammatory responses after small incision lenticule extraction (SMILE) versus femtosecond laser laser in situ keratomileusis (LASIK). Methods Thirty-six eyes of 36 rabbits underwent SMILE, while another 36 eyes of 36 rabbits were treated with femtosecond laser LASIK. All the eyes were subjected to the same refractive correction of −6.00 DS/−1.00 DC. Twelve eyes that had no surgery were included for control. After euthanisation, corneal tissue sections were evaluated with terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labelling (TUNEL) assay to detect apoptosis at postoperative 4 and 24 h, immunocytochemistry for Ki67 to detect keratocyte proliferation at postoperative day 3, week 1 and month 1, and immunocytochemistry for CD11b to detect inflammation at postoperative day 1, day 3 and week 1, respectively. Results No adverse effects were noted after SMILE or LASIK. Corneal healing postoperatively was uneventful in all cases. There were significantly fewer TUNEL-positive corneal stromal cells after the SMILE procedure at 4 and 24 h postoperatively (p<0.01) compared with the LASIK procedure. In addition, immunocytochemistry showed significantly fewer Ki67-positive cells in the SMILE group than those in the femtosecond laser LASIK group at day 3 and week 1 postoperatively (p<0.05), but there was little expression of Ki67 at month 1 postoperatively in both groups. The CD11b-positive cells were significantly fewer in the SMILE group at day 1, day 3 and week 1 postoperatively (p<0.01). Conclusions SMILE induces less keratocyte apoptosis, proliferation and inflammation compared with femtosecond laser LASIK. PMID:24227802

  3. Laser-induced corneal cross-linking upon photorefractive ablation with riboflavin

    PubMed Central

    Kornilovskiy, Igor M; Kasimov, Elmar M; Sultanova, Ayten I; Burtsev, Alexander A

    2016-01-01

    Aim To estimate the biomechanical effect of the laser-induced cross-linking resulting from photorefractive ablation of the cornea with riboflavin. Methods Excimer laser ablation studies were performed ex vivo (32 eyes of 16 rabbits) by phototherapeutic keratectomy (PTK) and in vivo (24 eyes of 12 rabbits) by transepithelial photorefractive keratectomy (TransPRK), with and without riboflavin saturation of the stroma. Then, we performed corneal optical coherence tomography on 36 eyes of 18 patients with varying degrees of myopia at different times after the TransPRK was performed with riboflavin saturation of the stroma. Results Biomechanical testing of corneal samples saturated with riboflavin revealed cross-linking effect accompanied by the increase in tensile strength and maximum strength. PTK showed increase in tensile strength from 5.1±1.4 to 7.2±1.6 MPa (P=0.001), while Trans-PRK showed increase in tensile strength from 8.8±0.9 to 12.8±1.3 MPa (P=0.0004). Maximum strength increased from 8.7±2.5 to 12.0±2.8 N (P=0.005) in PTK and from 12.8±1.6 to 18.3±1.2 N (P=0.0004) in TransPRK. Clinical optical coherence tomography studies of the biomicroscopic transparent cornea at different times after TransPRK showed increased density in the surface layers of the stroma and membrane-like structure beneath the epithelium. Conclusion Photorefractive ablation of the preliminary corneal stroma saturation with riboflavin causes the effect of laser-induced cross-linking, which is attended with an increase in corneal tensile strength, maximum strength, increased density in the surface layers of the stroma, and formation of a membrane-like structure beneath the epithelium after TransPRK. PMID:27099467

  4. Corneal thermal damage threshold dependence on the exposure duration for near-infrared laser radiation at 1319 nm

    NASA Astrophysics Data System (ADS)

    Wang, Jiarui; Jiao, Luguang; Chen, Hongxia; Yang, Zaifu; Hu, Xiangjun

    2016-01-01

    The corneal damage effects induced by 1319-nm transitional near-infrared laser have been investigated for years. However, the damage threshold dependence on exposure duration has not been revealed. The in vivo corneal damage thresholds (ED50s) were determined in New Zealand rabbits for 1319-nm laser radiation for exposure durations from 75 ms to 10 s. An additional corneal ED50 was determined at 1338 nm for a 5-ms exposure. The incident corneal irradiance diameter was fixed at 2 mm for all exposure conditions to avoid the influence of spot size on threshold. The ED50s given in terms of the corneal radiant exposure for exposure durations of 5 ms, 75 ms, 0.35 s, 2 s, and 10 s were 39.4, 51.5, 87.2, 156.3, and 311.1 J/cm2, respectively. The 39.4 J/cm2 was derived from the ED50 for 1338 nm (27.0 J/cm2). The ED50s for exposure durations of 75 ms to 10 s were correlated by a power law equation, ED50=128.9t0.36 in J/cm2, where t was the input in the unit of second, with correlation coefficient (R) of 0.997. Enough safe margins existed between the ED50s and the maximum permitted exposures from current laser safety standard.

  5. Amniotic membrane immobilized poly(vinyl alcohol) hybrid polymer as an artificial cornea scaffold that supports a stratified and differentiated corneal epithelium.

    PubMed

    Uchino, Yuichi; Shimmura, Shigeto; Miyashita, Hideyuki; Taguchi, Tetsushi; Kobayashi, Hisatoshi; Shimazaki, Jun; Tanaka, Junzo; Tsubota, Kazuo

    2007-04-01

    Poly(vinyl alcohol) (PVA) is a biocompatible, transparent hydrogel with physical strength that makes it promising as a material for an artificial cornea. In our previous study, type I collagen was immobilized onto PVA (PVA-COL) as a possible artificial cornea scaffold that can sustain a functional corneal epithelium. The cellular adhesiveness of PVA in vitro was improved by collagen immobilization; however, stable epithelialization was not achieved in vivo. To improve epithelialization in vivo, we created an amniotic membrane (AM)-immobilized polyvinyl alcohol hydrogel (PVA-AM) for use as an artificial cornea material. AM was attached to PVA-COL using a tissue adhesive consisting of collagen and citric acid derivative (CAD) as a crosslinker. Rabbit corneal epithelial cells were air-lift cultured with 3T3 feeder fibroblasts to form a stratified epithelial layer on PVA-AM. The rabbit corneal epithelial cells formed 3-5 layers of keratin-3-positive epithelium on PVA-AM. Occludin-positive cells were observed lining the superficial epithelium, the gap-junctional protein connexin43-positive cells was localized to the cell membrane of the basal epithelium, while both collagen IV were observed in the basement membrane. Epithelialization over implanted PVA-AM was complete within 2 weeks, with little inflammation or opacification of the hydrogel. Corneal epithelialization on PVA-AM in rabbit corneas improved over PVA-COL, suggesting the possibility of using PVA-AM as a biocompatible hybrid material for keratoprosthesis. PMID:16924609

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

    PubMed Central

    Lai, Jui-Yang

    2015-01-01

    The development of porous hyaluronic acid (HA) hydrogels for corneal endothelial tissue engineering is attractive because they can be used as functional cell delivery carriers to help in the reconstruction of damaged areas. The purpose of this study was to investigate the corneal endothelial cytocompatibility and cell delivery performance of porous HA hydrogel biomaterials fabricated at different pre-freezing temperatures. As compared to their counterparts prepared at −80 °C, the HA samples fabricated at higher pre-freezing temperature (i.e., 0 °C) exhibited a larger pore size and higher porosity, thereby leading to lower resistance to glucose permeation. Live/dead assays and gene expression analyses showed that the restricted porous structure of HA carriers decreases the viability and ionic pump function of cultured corneal endothelial cells (CECs). The results also indicated that the porous hydrogel biomaterials fabricated at high pre-freezing temperature seem to be more compatible with rabbit CECs. In an animal model of corneal endothelial dysfunction, the wounded rabbit corneas receiving bioengineered CEC sheets and restricted porous-structured HA carriers demonstrated poor tissue reconstruction. The therapeutic efficacy of cell sheet transplants can be improved by using carrier materials prepared at high pre-freezing temperature. Our findings suggest that the cryogenic operation temperature-mediated pore microstructure of HA carriers plays an important role in corneal endothelial cytocompatibility and cell delivery performance. PMID:26270663

  7. Thrombomodulin Promotes Corneal Epithelial Wound Healing

    PubMed Central

    Huang, Yi-Hsun; I, Ching-Chang; Kuo, Cheng-Hsiang; Hsu, Yun-Yan; Lee, Fang-Tzu; Shi, Guey-Yueh; Tseng, Sung-Huei; Wu, Hua-Lin

    2015-01-01

    Purpose To determine the role of thrombomodulin (TM) in corneal epithelial wound healing, and to investigate whether recombinant TM epidermal growth factor-like domain plus serine/threonine-rich domain (rTMD23) has therapeutic potential in corneal epithelial wound healing. Methods TM localization and expression in the murine cornea were examined by immunofluorescence staining. TM expression after injury was also studied. The effect of rTMD23 on corneal wound healing was evaluated by in vitro and in vivo assays. Results TM was expressed in the cornea in normal adult mice. TM expression increased in the early phase of wound healing and decreased after wound recovery. In the in vitro study, platelet-derived growth factor-BB (PDGF-BB) induced TM expression in murine corneal epithelial cells by mediating E26 transformation-specific sequence-1 (Ets-1) via the mammalian target of rapamycin (mTOR) signaling pathway. The administration of rTMD23 increased the rate of corneal epithelial wound healing. Conclusions TM expression in corneal epithelium was modulated during the corneal wound healing process, and may be regulated by PDGF-BB. In addition, rTMD23 has therapeutic potential in corneal injury. PMID:25816372

  8. [Corneal tatoo--art or science?].

    PubMed

    Craiu, Andreea-Madalina

    2009-01-01

    The permanent colouring of disfigured corneal scars is known for almost 200 years. Because of improvement in surgical reconstructive techniques, corneal tattoing is used today only with a restricted group on carefully chosen patients, and merely for esthetique reasons. PMID:19697848

  9. Corneal hysteresis and its relevance to glaucoma

    PubMed Central

    Deol, Madhvi; Taylor, David A.; Radcliffe, Nathan M.

    2015-01-01

    Purpose of review Glaucoma is a leading cause of irreversible blindness worldwide. It is estimated that roughly 60.5 million people had glaucoma in 2010 and that this number is increasing. Many patients continue to lose vision despite apparent disease control according to traditional risk factors. The purpose of this review is to discuss the recent findings with regard to corneal hysteresis, a variable that is thought to be associated with the risk and progression of glaucoma. Recent findings Low corneal hysteresis is associated with optic nerve and visual field damage in glaucoma and the risk of structural and functional glaucoma progression. In addition, hysteresis may enhance intraocular pressure (IOP) interpretation: low corneal hysteresis is associated with a larger magnitude of IOP reduction following various glaucoma therapies. Corneal hysteresis is dynamic and may increase in eyes after IOP-lowering interventions are implemented. Summary It is widely accepted that central corneal thickness is a predictive factor for the risk of glaucoma progression. Recent evidence shows that corneal hysteresis also provides valuable information for several aspects of glaucoma management. In fact, corneal hysteresis may be more strongly associated with glaucoma presence, risk of progression, and effectiveness of glaucoma treatments than central corneal thickness. PMID:25611166

  10. 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 DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1220 Corneal electrode. (a) Identification. A...

  11. Development of a Zealand white rabbit deposition model to study inhalation anthrax.

    PubMed

    Asgharian, Bahman; Price, Owen; Kabilan, Senthil; Jacob, Richard E; Einstein, Daniel R; Kuprat, Andrew P; Corley, Richard A

    2016-02-01

    Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits as a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits. PMID:26895308

  12. Paracellular and passive transcellular permeability in immortalized human corneal epithelial cell culture model.

    PubMed

    Toropainen, Elisa; Ranta, Veli-Pekka; Vellonen, Kati-Sisko; Palmgrén, Joni; Talvitie, Anu; Laavola, Mirka; Suhonen, Pekka; Hämäläinen, Kaisa Mari; Auriola, Seppo; Urtti, Arto

    2003-09-01

    A cell culture model of human corneal epithelium (HCE-model) was recently introduced [Invest. Ophthalmol. Vis. Sci. 42 (2001) 2942] as a tool for ocular drug permeation studies. In this study, passive permeability and esterase activity of the HCE-model were characterised. Immortalised human corneal epithelial cells were grown on collagen coated filters under air-lift. The sensitivity of transcellular permeability to lipophilicity was tested in studies using nine beta-blockers. The size selectivity of the paracellular route was investigated using 16 polyethylene glycol oligomers (PEG). An effusion-like approach was used to estimate porosity and pore sizes of the paracellular space in HCE membrane. Permeability and degradation of fluorescein diacetate to fluorescein in HCE-cells was used to probe the esterase activity of the HCE-model. Drug concentrations were analyzed using HPLC (beta-blockers), LC-MS (PEGs), and fluorometry (fluorescein). Permeabilities were compared to those in the excised rabbit cornea. Penetration of beta-blockers increased with lipophilicity according to a sigmoidal relationship. This was almost similar to the profile in excised cornea. No apical to basolateral directionality was seen in the permeation of beta-blockers. Paracellular permeability of the HCE-model was generally slightly higher than that of the excised rabbit cornea. The HCE-model has larger paracellular pores, but lower pore density than the excised cornea, but the overall paracellular space was fairly similar in both models. The HCE-model shows significant esterase activity (i.e. fluorescein diacetate was converted to free fluorescein). These data on permeability of 27 compounds demonstrate that the barrier of the HCE-model closely resembles that of the excised rabbit cornea. Therefore, the HCE-model is a promising alternative corneal substitute for ocular drug delivery studies. PMID:13678798

  13. Riboflavin for corneal cross-linking.

    PubMed

    O'Brart, D P S

    2016-06-01

    Corneal collagen cross-linking (CXL) with riboflavin and ultraviolet A (UVA) radiation is the first therapeutic modality that appears to arrest the progression of keratoconus and other corneal ectasias. Riboflavin is central to the process, acting as a photosensitizer for the production of oxygen singlets and riboflavin triplets. These free radicals drive the CXL process within the proteins of the corneal stroma, altering its biomechanical properties. Riboflavin also absorbs the majority of the UVA radiation, which is potentially cytotoxic and mutagenic, within the anterior stroma, preventing damage to internal ocular structures, such as the corneal endothelium, lens and retina. Clinical studies report cessation of ectatic progression in over 90% of cases and the majority document significant improvements in visual, keratometric and topographic parameters. Clinical follow-up is limited to 5-10 years, but suggests sustained stability and enhancement in corneal shape. Sight-threatening complications are rare. The optimal stromal riboflavin dosage for CXL is as yet undetermined. PMID:27458610

  14. Corneal autofluorescence in presence of diabetic retinopathy

    NASA Astrophysics Data System (ADS)

    Rovati, Luigi; Docchio, Franco; Azzolini, Claudio; Van Best, Jaap A.

    1998-06-01

    Recently corneal autofluorescence has been proposed as an ocular diagnostic tool for diabetic retinopathy. The method is based on the sensible increase of the natural fluorescence of corneal tissue within specific wavelength in presence of early stage of diabetic retinopathy. The main advantages of this method are that the corneal autofluorescence has been demonstrated to be not age-related and that the cornea is readily accessible to be investigated. In this study 47 insulin-dependent diabetes mellitus and 51 non-insulin- dependent diabetes mellitus patients aged 20 - 90 years have been considered. Patients were selected from the Eye Clinic of S. Raffaele Hospital. The modified Airlie House classification was used to grade the diabetic retinopathy. Corneal autofluorescence has been measured by using both a specifically designed instrument and the Fluorotron Master. Corneal autofluorescence mean value for each diabetic retinopathy measured by using both the instruments correlated with the retinopathy grade.

  15. Corneal abrasions associated with pepper spray exposure.

    PubMed

    Brown, L; Takeuchi, D; Challoner, K

    2000-05-01

    Pepper spray containing oleoresin capsicum is used by law enforcement and the public as a form of nonlethal deterrent. Stimulated by the identification of a case of a corneal abrasion associated with pepper spray exposure, a descriptive retrospective review of a physician-maintained log of patients presenting to a jail ward emergency area over a 3-year period was performed. The objective was to give some quantification to the frequency with which an emergency physician could expect to see corneal abrasions associated with pepper spray exposure. Of 100 cases of pepper spray exposure identified, seven patients had sustained corneal abrasions. We conclude that corneal abrasions are not rare events when patients are exposed to pepper spray and that fluorescein staining and slit lamp or Wood's lamp examination should be performed on all exposed patients in whom corneal abrasions cannot be excluded on clinical grounds. PMID:10830682

  16. Imaging Mass Spectrometry by Matrix-Assisted Laser Desorption/Ionization and Stress-Strain Measurements in Iontophoresis Transepithelial Corneal Collagen Cross-Linking

    PubMed Central

    Mencucci, Rita; Camesasca, Fabrizio I.; Favuzza, Eleonora

    2014-01-01

    Purpose. To compare biomechanical effect, riboflavin penetration and distribution in transepithelial corneal collagen cross-linking with iontophoresis (I-CXL), with standard cross linking (S-CXL) and current transepithelial protocol (TE-CXL). Materials and Methods. The study was divided into two different sections, considering, respectively, rabbit and human cadaver corneas. In both sections corneas were divided according to imbibition protocols and irradiation power. Imaging mass spectrometry by matrix-assisted laser desorption/ionization (MALDI-IMS) and stress-strain measurements were used. Forty-eight rabbit and twelve human cadaver corneas were evaluated. Results. MALDI-IMS showed a deep riboflavin penetration throughout the corneal layers with I-CXL, with a roughly lower concentration in the deepest layers when compared to S-CXL, whereas with TE-CXL penetration was considerably less. In rabbits, there was a significant increase (by 71.9% and P = 0.05) in corneal rigidity after I-CXL, when compared to controls. In humans, corneal rigidity increase was not significantly different among the subgroups. Conclusions. In rabbits, I-CXL induced a significant increase in corneal stiffness as well as better riboflavin penetration when compared to controls and TE-CXL but not to S-CXL. Stress-strain in human corneas did not show significant differences among techniques, possibly because of the small sample size of groups. In conclusion, I-CXL could be a valid alternative to S-CXL for riboflavin delivery in CXL, preserving the epithelium. PMID:25276786

  17. Corneal endothelium: developmental strategies for regeneration

    PubMed Central

    Zavala, J; López Jaime, G R; Rodríguez Barrientos, C A; Valdez-Garcia, J

    2013-01-01

    The main treatment available for restoration of the corneal endothelium is keratoplasty. This procedure is faced with several difficulties, including the shortage of donor tissue, post-surgical complications associated with the use of drugs to prevent immune rejection, and a significant increase in the occurrence of glaucoma. Recently, surgical procedures such as Descemet's stripping endothelial keratoplasty have focused on the transplant of corneal endothelium, yielding better visual results but still facing the need for donor tissue. The emergent strategies in the field of cell biology and tissue cultivation of corneal endothelial cells aim at the production of transplantable endothelial cell sheets. Cell therapy focuses on the culture of corneal endothelial cells retrieved from the donor, in the donor's cornea, followed by transplantation into the recipient. Recently, research has focused on overcoming the challenge of harvesting human corneal endothelial cells and the generation of new biomembranes to be used as cell scaffolds in surgical procedures. The use of corneal endothelial precursors from the peripheral cornea has also demonstrated to be effective and represents a valuable tool for reducing the risk of rejection in allogeneic transplants. Several animal model reports also support the use of adult stem cells as therapy for corneal diseases. Current results represent important progresses in the development of new strategies based on alternative sources of tissue for the treatment of corneal endotheliopathies. Different databases were used to search literature: PubMed, Google Books, MD Consult, Google Scholar, Gene Cards, and NCBI Books. The main search terms used were: ‘cornea AND embryology AND transcription factors', ‘human endothelial keratoplasty AND risk factors', ‘(cornea OR corneal) AND (endothelium OR endothelial) AND cell culture', ‘mesenchymal stem cells AND cell therapy', ‘mesenchymal stem cells AND cornea', and ‘stem cells AND

  18. Differential diagnosis of Schnyder corneal dystrophy.

    PubMed

    Weiss, Jayne S; Khemichian, Arbi J

    2011-01-01

    Schnyder corneal dystrophy (SCD) is a rare corneal dystrophy characterized by abnormally increased deposition of cholesterol and phospholipids in the cornea leading to progressive vision loss. SCD is inherited as an autosomal dominant trait with high penetrance and has been mapped to the UBIAD1 gene on chromosome 1p36.3. Although 2/3 of SCD patients also have systemic hypercholesterolemia, the incidence of hypercholesterolemia is also increased in unaffected members of SCD pedigrees. Consequently, SCD is thought to result from a local metabolic defect in the cornea. The corneal findings in SCD are very predictable depending on the age of the individual, with initial central corneal haze and/or crystals, subsequent appearance of arcus lipoides in the third decade and formation of midperipheral haze in the late fourth decade. Because only 50% of affected patients have corneal crystals, the International Committee for Classification of Corneal Dystrophies recently changed the original name of this dystrophy from Schnyder crystalline corneal dystrophy to Schnyder corneal dystrophy. Diagnosis of affected individuals without crystalline deposits is often delayed and these individuals are frequently misdiagnosed. The differential diagnosis of the SCD patient includes other diseases with crystalline deposits such as cystinosis, tyrosinemia, Bietti crystalline dystrophy, hyperuricemia/gout, multiple myeloma, monoclonal gammopathy, infectious crystalline keratopathy, and Dieffenbachia keratitis. Depositions from drugs such as gold in chrysiasis, chlorpromazine, chloroquine, and clofazamine can also result in corneal deposits and are different from SCD. Diseases of systemic lipid metabolism that cause corneal opacification, such as lecithin-cholesterol acyltransferase deficiency, fish eye disease and Tangier disease, should also be considered although these are autosomal recessive disorders. PMID:21540632

  19. Posterior corneal curvature changes following Refractive Small Incision Lenticule Extraction

    PubMed Central

    Ganesh, Sri; Patel, Utsav; Brar, Sheetal

    2015-01-01

    Purpose To compare the posterior corneal curvature changes, in terms of corneal power and asphercity, following Refractive Small Incision Lenticule Extraction (ReLEx SMILE) procedure for low, moderate, and high myopia. Methods This retrospective, non randomized, comparative, interventional trial; included 52 eyes of 26 patients, divided in three groups: low myopia (myopia ≤3 D [diopters] spherical equivalent [SE]), moderate myopia (myopia >3 D and <6 D SE), and high myopia (myopia ≥6 D SE). All patients were treated for myopia and myopic astigmatism using ReLEx SMILE. The eyes were examined pre-operatively and 3 months post-operatively using SCHWIND SIRIUS, a three-dimensional rotating Scheimpflug camera with a Placido disc topographer to assess corneal changes with regard to keratometric power and asphericity of the cornea. Results A statistically significant increase in mean keratometric power in the 3, 5, and 7 mm zones of the posterior corneal surface compared with its pre-ReLEx SMILE value was detected after 3 months in the moderate myopia group (pre-operative [pre-op] −6.14±0.23, post-operative [post-op] −6.29±0.22, P<0.001) and high myopia group (pre-op −6.19±0.16, post-op −6.4±0.18, P<0.001), but there was no significant change in keratometric power of the posterior surface in the low myopia group (pre-op −5.87±0.17, post-op −6.06±0.29, P=0.143). Asphericity (Q-value) of the posterior surface changed significantly (P<0.001) after ReLEx SMILE in the moderate myopia group in the 3, 5, and 7 mm zones, and in the high myopia group in the 3 and 7 mm zones; but there was no significant change in the Q-value in the low myopia group in all three zones (pre-op 0.23±0.43, post-op −0.40±0.71, P=0.170), and in the high myopia group in the 5 mm zone (P=0.228). Conclusion ReLEx SMILE causes significant changes in posterior corneal keratometric power and asphericity in moderate and high myopia, but the effect is subtle and insignificant in low

  20. The Impact of Type 1 Diabetes Mellitus on Corneal Epithelial Nerve Morphology and the Corneal Epithelium

    PubMed Central

    Cai, Daniel; Zhu, Meifang; Petroll, W. Matthew; Koppaka, Vindhya; Robertson, Danielle M.

    2015-01-01

    Diabetic corneal neuropathy can result in chronic, sight-threatening corneal pathology. Although the exact etiology is unknown, it is believed that a reduction in corneal sensitivity and loss of neurotrophic support contributes to corneal disease. Information regarding the relationship between nerve loss and effects on the corneal epithelium is limited. We investigated changes in the corneal epithelium and nerve morphology using three-dimensional imaging in vivo and in situ in a streptozotocin-induced diabetic mouse model. Streptozotocin-treated mice showed increased levels of serum glucose and growth retardation consistent with a severe diabetic state. A reduction in the length of the subbasal nerve plexus was evident after 6 weeks of disease. Loss of the subbasal nerve plexus was associated with corneal epithelial thinning and a reduction in basal epithelial cell density. In contrast, loss of the terminal epithelial nerves was associated with animal age. Importantly, this is the first rodent model of type 1 diabetes that shows characteristics of corneal epithelial thinning and a reduction in basal epithelial cell density, both previously have been documented in humans with diabetic corneal neuropathy. These findings indicate that in type 1 diabetes, nerve fiber damage is evident in the subbasal nerve plexus before terminal epithelial nerve loss and that neurotrophic support from both the subbasal nerve plexus and terminal epithelial nerves is essential for the maintenance of corneal epithelial homeostasis. PMID:25102563

  1. The impact of type 1 diabetes mellitus on corneal epithelial nerve morphology and the corneal epithelium.

    PubMed

    Cai, Daniel; Zhu, Meifang; Petroll, W Matthew; Koppaka, Vindhya; Robertson, Danielle M

    2014-10-01

    Diabetic corneal neuropathy can result in chronic, sight-threatening corneal pathology. Although the exact etiology is unknown, it is believed that a reduction in corneal sensitivity and loss of neurotrophic support contributes to corneal disease. Information regarding the relationship between nerve loss and effects on the corneal epithelium is limited. We investigated changes in the corneal epithelium and nerve morphology using three-dimensional imaging in vivo and in situ in a streptozotocin-induced diabetic mouse model. Streptozotocin-treated mice showed increased levels of serum glucose and growth retardation consistent with a severe diabetic state. A reduction in the length of the subbasal nerve plexus was evident after 6 weeks of disease. Loss of the subbasal nerve plexus was associated with corneal epithelial thinning and a reduction in basal epithelial cell density. In contrast, loss of the terminal epithelial nerves was associated with animal age. Importantly, this is the first rodent model of type 1 diabetes that shows characteristics of corneal epithelial thinning and a reduction in basal epithelial cell density, both previously have been documented in humans with diabetic corneal neuropathy. These findings indicate that in type 1 diabetes, nerve fiber damage is evident in the subbasal nerve plexus before terminal epithelial nerve loss and that neurotrophic support from both the subbasal nerve plexus and terminal epithelial nerves is essential for the maintenance of corneal epithelial homeostasis. PMID:25102563

  2. Corneal Fibroblast Migration Patterns During Intrastromal Wound Healing Correlate With ECM Structure and Alignment

    PubMed Central

    Petroll, W. Matthew; Kivanany, Pouriska B.; Hagenasr, Daniela; Graham, Eric K.

    2015-01-01

    Purpose To assess keratocyte backscattering, alignment, morphology, and connectivity in vivo following a full-thickness corneal injury using the Heidelberg Retina Tomograph Rostock Cornea Module (HRT-RCM), and to correlate these findings with en bloc three-dimensional (3-D) confocal fluorescence and second harmonic generation (SHG) imaging. Methods Rabbit corneas were scanned in vivo both before and 3, 7, 14, and 28 days after transcorneal freeze injury (FI), which damages all corneal cell layers. Corneal tissue was also fixed and labeled for f-actin and nuclei en bloc, and imaged using 3-D confocal fluorescence microscopy and SHG imaging. Results Using the modified HRT-RCM, full-thickness scans of all cell layers were consistently obtained. Following FI, stromal cells repopulating the damaged tissue assumed an elongated fibroblastic morphology, and a significant increase in cellular light scattering was measured. This stromal haze gradually decreased as wound healing progressed. Parallel, interconnected streams of aligned corneal fibroblasts were observed both in vivo (from HRT-RCM reflection images) and ex vivo (from f-actin and nuclear labeling) during wound healing, particularly in the posterior cornea. Second harmonic generation imaging demonstrated that these cells were aligned parallel to the collagen lamellae. Conclusions The modified HRT-RCM allows in vivo measurements of sublayer thickness, assessment of cell morphology, alignment and connectivity, and estimation of stromal backscatter during wound healing. In this study, these in vivo observations led to the novel finding that the pattern of corneal fibroblast alignment is highly correlated with lamellar organization, suggesting contact guidance of intrastromal migration that may facilitate more rapid wound repopulation. PMID:26562169

  3. Nanoscale modification of porous gelatin scaffolds with chondroitin sulfate for corneal stromal tissue engineering.

    PubMed

    Lai, Jui-Yang; Li, Ya-Ting; Cho, Ching-Hsien; Yu, Ting-Chun

    2012-01-01

    Recent studies reflect the importance of using naturally occurring biopolymers as three-dimensional corneal keratocyte scaffolds and suggest that the porous structure of gelatin materials may play an important role in controlling nutrient uptake. In the current study, the authors further consider the application of carbodiimide cross-linked porous gelatin as an alternative to collagen for corneal stromal tissue engineering. The authors developed corneal keratocyte scaffolds by nanoscale modification of porous gelatin materials with chondroitin sulfate (CS) using carbodiimide chemistry. Scanning electron microscopy/energy dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy showed that the amount of covalently incorporated polysaccharide was significantly increased when the CS concentration was increased from 0% to 1.25% (w/v). In addition, as demonstrated by dimethylmethylene blue assays, the CS content in these samples was in the range of 0.078-0.149 nmol per 10 mg scaffold. When compared with their counterparts without CS treatment, various CS-modified porous gelatin membranes exhibited higher levels of water content, light transmittance, and amount of permeated nutrients but possessed lower Young's modulus and resistance against protease digestion. The hydrophilic and mechanical properties of scaffolds modified with 0.25% CS were comparable with those of native corneas. The samples from this group were biocompatible with the rabbit corneal keratocytes and showed enhanced proliferative and biosynthetic capacity of cultured cells. In summary, the authors found that the nanoscale-level modification has influence on the characteristics and cell-material interactions of CS-containing gelatin hydrogels. Porous membranes with a CS content of 0.112 ± 0.003 nmol per 10 mg scaffold may hold potential for use in corneal stromal tissue engineering. PMID:22403490

  4. Nanoscale modification of porous gelatin scaffolds with chondroitin sulfate for corneal stromal tissue engineering

    PubMed Central

    Lai, Jui-Yang; Li, Ya-Ting; Cho, Ching-Hsien; Yu, Ting-Chun

    2012-01-01

    Recent studies reflect the importance of using naturally occurring biopolymers as three-dimensional corneal keratocyte scaffolds and suggest that the porous structure of gelatin materials may play an important role in controlling nutrient uptake. In the current study, the authors further consider the application of carbodiimide cross-linked porous gelatin as an alternative to collagen for corneal stromal tissue engineering. The authors developed corneal keratocyte scaffolds by nanoscale modification of porous gelatin materials with chondroitin sulfate (CS) using carbodiimide chemistry. Scanning electron microscopy/energy dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy showed that the amount of covalently incorporated polysaccharide was significantly increased when the CS concentration was increased from 0% to 1.25% (w/v). In addition, as demonstrated by dimethylmethylene blue assays, the CS content in these samples was in the range of 0.078–0.149 nmol per 10 mg scaffold. When compared with their counterparts without CS treatment, various CS-modified porous gelatin membranes exhibited higher levels of water content, light transmittance, and amount of permeated nutrients but possessed lower Young’s modulus and resistance against protease digestion. The hydrophilic and mechanical properties of scaffolds modified with 0.25% CS were comparable with those of native corneas. The samples from this group were biocompatible with the rabbit corneal keratocytes and showed enhanced proliferative and biosynthetic capacity of cultured cells. In summary, the authors found that the nanoscale-level modification has influence on the characteristics and cell-material interactions of CS-containing gelatin hydrogels. Porous membranes with a CS content of 0.112 ± 0.003 nmol per 10 mg scaffold may hold potential for use in corneal stromal tissue engineering. PMID:22403490

  5. 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

  6. First Identification of a Triple Corneal Dystrophy Association: Keratoconus, Epithelial Basement Membrane Corneal Dystrophy and Fuchs’ Endothelial Corneal Dystrophy

    PubMed Central

    Mazzotta, Cosimo; Traversi, Claudio; Raiskup, Frederik; Rizzo, Caterina Lo; Renieri, Alessandra

    2014-01-01

    Purpose To report the observation of a triple corneal dystrophy association consisting of keratoconus (KC), epithelial basement membrane corneal dystrophy (EBMCD) and Fuchs’ endothelial corneal dystrophy (FECD). Methods A 55-year-old male patient was referred to our cornea service for blurred vision and recurrent foreign body sensation. He reported bilateral recurrent corneal erosions with diurnal visual fluctuations. He underwent corneal biomicroscopy, Scheimpflug tomography, in vivo HRT confocal laser scanning microscopy and genetic testing for TGFBI and ZEB1 mutations using direct DNA sequencing. Results Biomicroscopic examination revealed the presence of subepithelial central and paracentral corneal opacities. The endothelium showed a bilateral flecked appearance, and the posterior corneal curvature suggested a possible concomitant ectatic disorder. Corneal tomography confirmed the presence of a stage II KC in both eyes. In vivo confocal laser scanning microscopy revealed a concomitant bilateral EBMCD with hyperreflective deposits in basal epithelial cells, subbasal Bowman's layer microfolds and ridges with truncated subbasal nerves as pseudodendritic elements. Stromal analysis revealed honeycomb edematous areas, and the endothelium showed a strawberry surface configuration typical of FECD. The genetic analysis resulted negative for TGFBI mutations and positive for a heterozygous mutation in exon 7 of the gene ZEB1. Conclusion This is the first case reported in the literature in which KC, EBMCD and FECD are present in the same patient and associated with ZEB1 gene mutation. The triple association was previously established by means of morphological analysis of the cornea using corneal Scheimpflug tomography and in vivo HRT II confocal laser scanning microscopy. PMID:25408666

  7. [Influence of corneal transparency on the quality of topographies].

    PubMed

    Franko Zeitz, P; Kohlhaas, M

    2012-12-01

    Corneal topographs that measure the anterior and posterior corneal surface with optical methods need a clear cornea for precise measurements. Opacities cause artifacts in the corneal thickness (with measurements usually being too thin) and corneal curvatures. This is important to know as certain pathologies may repeatedly cause similar artifacts. This is highly relevant after a corneal cross-linking, Lasek or PRK, as these procedures cause typical artifacts that can easily be misinterpreted. PMID:23258670

  8. Terahertz sensing in corneal tissues

    PubMed Central

    Bennett, David B.; Taylor, Zachary D.; Tewari, Pria; Singh, Rahul S.; Culjat, Martin O.; Grundfest, Warren S.; Sassoon, Daniel J.; Johnson, R. Duncan; Hubschman, Jean-Pierre; Brown, Elliott R.

    2011-01-01

    This work introduces the potential application of terahertz (THz) sensing to the field of ophthalmology, where it is uniquely suited due to its nonionizing photon energy and high sensitivity to water content. Reflective THz imaging and spectrometry data are reported on ex-vivo porcine corneas prepared with uniform water concentrations using polyethylene glycol (PEG) solutions. At 79% water concentration by mass, the measured reflectivity of the cornea was 20.4%, 14.7%, 11.7%, 9.6%, and 7.4% at 0.2, 0.4, 0.6, 0.8, and 1 THz, respectively. Comparison of nine corneas hydrated from 79.1% to 91.5% concentration by mass demonstrated an approximately linear relationship between THz reflectivity and water concentration, with a monotonically decreasing slope as the frequency increases. The THz-corneal tissue interaction is simulated with a Bruggeman model with excellent agreement. THz applications to corneal dystrophy, graft rejection, and refractive surgery are examined from the context of these measurements. PMID:21639581

  9. 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

  10. Corneal nerves in health and disease.

    PubMed

    Shaheen, Brittany Simmons; Bakir, May; Jain, Sandeep

    2014-01-01

    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 neuroregenerative and inflammatory pathways in the cornea are intertwined. Evidence-based treatment of neurotrophic corneal diseases includes using neuroregenerative (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

  11. Corneal laceration caused by river crab

    PubMed Central

    Vinuthinee, Naidu; Azreen-Redzal, Anuar; Juanarita, Jaafar; Zunaina, Embong

    2015-01-01

    A 5-year-old boy presented with right eye pain associated with tearing and photophobia of 1-day duration. He gave a history of playing with a river crab when suddenly the crab clamped his fingers. He attempted to fling the crab off, but the crab flew and hit his right eye. Ocular examination revealed a right eye corneal ulcer with clumps of fibrin located beneath the corneal ulcer and 1.6 mm level of hypopyon. At presentation, the Seidel test was negative, with a deep anterior chamber. Culture from the corneal scrapping specimen grew Citrobacter diversus and Proteus vulgaris, and the boy was treated with topical gentamicin and ceftazidime eyedrops. Fibrin clumps beneath the corneal ulcer subsequently dislodged, and revealed a full-thickness corneal laceration wound with a positive Seidel test and shallow anterior chamber. The patient underwent emergency corneal toileting and suturing. Postoperatively, he was treated with oral ciprofloxacin 250 mg 12-hourly for 1 week, topical gentamicin, ceftazidime, and dexamethasone eyedrops for 4 weeks. Right eye vision improved to 6/9 and 6/6 with pinhole at the 2-week follow-up following corneal suture removal. PMID:25678769

  12. Molecular Bases of Corneal Endothelial Dystrophies

    PubMed Central

    Schmedt, Thore; Silva, Mariana Mazzini; Ziaei, Alireza; Jurkunas, Ula

    2011-01-01

    The phrase “corneal endothelial dystrophies” embraces a group of bilateral corneal conditions that are characterized by a non-inflammatory and progressive degradation of corneal endothelium. Corneal endothelial cells exhibit a high pump site density and, along with barrier function, are responsible for maintaining the cornea in its natural state of relative dehydration. Gradual loss of endothelial cells leads to an insufficient water outflow, resulting in corneal edema and loss of vision. Since the pathologic mechanisms remain largely unknown, the only current treatment option is surgical transplantation when vision is severely impaired. In the past decade, important steps have been taken to understand how endothelial degeneration progresses on the molecular level. Studies of affected multigenerational families and sporadic cases identified genes and chromosomal loci, and revealed either Mendelian or complex disorder inheritance patterns. Mutations have been detected in genes that carry important structural, metabolic, cytoprotective, and regulatory functions in corneal endothelium. In addition to genetic predisposition, environmental factors like oxidative stress were found to be involved in the pathogenesis of endotheliopathies. This review summarizes and crosslinks the recent progress on deciphering the molecular bases of corneal endothelial dystrophies. PMID:21855542

  13. Corneal laceration caused by river crab.

    PubMed

    Vinuthinee, Naidu; Azreen-Redzal, Anuar; Juanarita, Jaafar; Zunaina, Embong

    2015-01-01

    A 5-year-old boy presented with right eye pain associated with tearing and photophobia of 1-day duration. He gave a history of playing with a river crab when suddenly the crab clamped his fingers. He attempted to fling the crab off, but the crab flew and hit his right eye. Ocular examination revealed a right eye corneal ulcer with clumps of fibrin located beneath the corneal ulcer and 1.6 mm level of hypopyon. At presentation, the Seidel test was negative, with a deep anterior chamber. Culture from the corneal scrapping specimen grew Citrobacter diversus and Proteus vulgaris, and the boy was treated with topical gentamicin and ceftazidime eyedrops. Fibrin clumps beneath the corneal ulcer subsequently dislodged, and revealed a full-thickness corneal laceration wound with a positive Seidel test and shallow anterior chamber. The patient underwent emergency corneal toileting and suturing. Postoperatively, he was treated with oral ciprofloxacin 250 mg 12-hourly for 1 week, topical gentamicin, ceftazidime, and dexamethasone eyedrops for 4 weeks. Right eye vision improved to 6/9 and 6/6 with pinhole at the 2-week follow-up following corneal suture removal. PMID:25678769

  14. Differences between real and predicted corneal shapes after aspherical corneal ablation.

    PubMed

    Anera, Rosario G; Villa, César; Jiménez, José R; Gutiérrez, Ramón; del Barco, Luis Jiménez

    2005-07-20

    We study the differences between real and expected corneal shapes, using an aspherical ablation algorithm with a known equation and avoiding the limitation imposed by most studies of refractive surgery in which the ablation equations are not known. We have calculated the theoretical corneal shape predicted by this algorithm, comparing this shape with the real corneal topography. The results indicate that the deviations that appear in the corneal shape are significant for visual performance and for the correction of eye aberrations. If we include in this analysis the effect of reflection losses and nonnormal incidence on the cornea, we can reduce corneal differences, but they will remain significant. These results confirm that it is essential to minimize corneal differences to achieve effective correction in refractive surgery. PMID:16047903

  15. Distribution of Posterior Corneal Astigmatism According to Axis Orientation of Anterior Corneal Astigmatism

    PubMed Central

    Miyake, Toshiyuki; Shimizu, Kimiya; Kamiya, Kazutaka

    2015-01-01

    Purpose To investigate the distribution of posterior corneal astigmatism in eyes with with-the-rule (WTR) and against-the-rule (ATR) anterior corneal astigmatism. Methods We retrospectively examined six hundred eight eyes of 608 healthy subjects (275 men and 333 women; mean age ± standard deviation, 55.3 ± 20.2 years). The magnitude and axis orientation of anterior and posterior corneal astigmatism were determined with a rotating Scheimpflug system (Pentacam HR, Oculus) when we divided the subjects into WTR and ATR anterior corneal astigmatism groups. Results The mean magnitudes of anterior and posterior corneal astigmatism were 1.14 ± 0.76 diopters (D), and 0.37 ± 0.19 D, respectively. We found a significant correlation between the magnitudes of anterior and posterior corneal astigmatism (Pearson correlation coefficient r = 0.4739, P<0.001). In the WTR anterior astigmatism group, we found ATR astigmatism of the posterior corneal surface in 402 eyes (96.6%). In the ATR anterior astigmatism group, we found ATR posterior corneal astigmatism in 82 eyes (73.9%). Especially in eyes with ATR anterior corneal astigmatism of 1 D or more and 1.5 D or more, ATR posterior corneal astigmatism was found in 28 eyes (59.6%) and 9 eyes (42.9%), respectively. Conclusions WTR anterior astigmatism and ATR posterior astigmatism were found in approximately 68% and 91% of eyes, respectively. The magnitude and the axis orientation of posterior corneal astigmatism were not constant, especially in eyes having high ATR anterior corneal astigmatism, as is often the case in patients who have undergone toric IOL implantation. PMID:25625283

  16. 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. PMID:27183635

  17. Technology needs for corneal transplant surgery

    NASA Astrophysics Data System (ADS)

    Vaddavalli, Pravin K.; Yoo, Sonia H.

    2011-03-01

    Corneal transplant surgery has undergone numerous modifications over the years with improvements in technique, instrumentation and eye banking. The main goals of corneal transplantation are achieving excellent optical clarity with long-term graft survival. Penetrating, anterior and posterior lamellar surgery along with femtosecond laser technology have partially met these goals, but outcomes are often unpredictable and surgeon dependent. Technology to predictably separate stroma from Descemet's membrane, techniques to minimize endothelial cell loss, improvements in imaging technology and emerging techniques like laser welding that might replace suturing, eventually making corneal transplantation a refractively predictable procedure are on the wish list of the cornea surgeon.

  18. Differential expression of epithelial basement membrane components nidogens and perlecan in corneal stromal cells in vitro

    PubMed Central

    Santhanam, Abirami; Torricelli, Andre A. M.; Wu, Jiahui; Marino, Gustavo K.

    2015-01-01

    Purpose The purpose of this study was to examine the expression of corneal epithelial basement membrane (EBM) components in different corneal stromal cell types. In vitro model systems were used to explore the expression of EBM components nidogen-1, nidogen-2, and perlecan that are the primary components in the lamina lucida and the lamina densa that defectively regenerate in corneas with stromal opacity after in −9.0 D photorefractive keratectomy (PRK). Methods Primary rabbit corneal stromal cells were cultured using varying serum concentrations and exogenous growth factors, including fibroblast growth factor (FGF)-2 and transforming growth factor (TGF)-β1, to optimize the growth of each cell type of interest. The expression of the keratocyte-specific marker keratocan and the myofibroblast-specific marker α-smooth muscle actin (α-SMA) were analyzed with real-time PCR, western blot, and immunocytochemical staining to evaluate the specificity of the cell types and select optimal conditions (high keratocan and low α-SMA for keratocytes; low keratocan and high α-SMA for myofibroblasts; low keratocan and low α-SMA for corneal fibroblasts). The expression of the EBM components nidogen-1, nidogen-2, and perlecan was evaluated in each corneal cell type using real-time PCR, immunostaining, and western blotting. In agreement with previous studies, serum-free DMEM was found to be optimal for keratocytes, DMEM with 10% serum and 40 ng/ml FGF-2 yielded the best marker profile for corneal fibroblasts, and DMEM with 1% serum and 2 ng/ml TGF-β1 was found to be optimal for myofibroblasts. Results Nidogen-1 and nidogen-2 mRNAs were highly expressed in keratocytes, whereas perlecan was highly expressed in myofibroblasts. In keratocytes, nidogen-2 and perlecan proteins were expressed predominantly in intracellular compartments, whereas in myofibroblasts expression of both EBM components was observed diffusely throughout the cell. Although the perlecan mRNA levels were high

  19. Inhibition of Corneal Neovascularization by Subconjunctival Injection of Fc-Endostatin, a Novel Inhibitor of Angiogenesis

    PubMed Central

    Yoshida, Junko; Wicks, Robert T.; Zambrano, Andrea I.; Tyler, Betty M.; Javaherian, Kashi; Grossman, Rachel; Daoud, Yassine J.; Gehlbach, Peter; Brem, Henry; Stark, Walter J.

    2015-01-01

    We assessed the antiangiogenic effects of subconjunctival injection of Fc-endostatin (FcE) using a human vascular endothelial growth factor-induced rabbit corneal neovascularization model. Angiogenesis was induced in rabbit corneas through intrastromal implantations of VEGF polymer implanted 2 mm from the limbus. NZW rabbits were separated into groups receiving twice weekly subconjunctival injections of either saline; 25 mg/mL bevacizumab; 2 mg/mL FcE; or 20 mg/mL FcE. Corneas were digitally imaged at 5 time points. An angiogenesis index (AI) was calculated (vessel length (mm) × vessel number score) for each observation. All treatment groups showed a significant decrease in the vessel length and AI compared to saline on all observation days (P < 0.001). By day 15, FcE 2 inhibited angiogenesis significantly better than FcE 20 (P < 0.01). There was no significant difference between FcE 2 and BV, although the values trended towards significantly increased inhibition by BV. BV was a significantly better inhibitor than FcE 20 by day 8 (P < 0.01). FcE was safe and significantly inhibited new vessel growth in a rabbit corneal neovascularization model. Lower concentration FcE 2 exhibited better inhibition than FcE 20, consistent with previous FcE studies referencing a biphasic dose-response curve. Additional studies are necessary to further elucidate the efficacy and clinical potential of this novel angiogenesis inhibitor. PMID:26491546

  20. Enhancing effects of sericin on corneal wound healing in rat debrided corneal epithelium.

    PubMed

    Nagai, Noriaki; Murao, Takatoshi; Ito, Yoshimasa; Okamoto, Norio; Sasaki, Masahiro

    2009-05-01

    The protein sericin is the main constituent of silk. We demonstrate the effects of sericin on corneal wound healing in rat debrided corneal epithelium. We also determined the effects of sericin on cell adhesion and proliferation in a human cornea epithelial cell line (HCE-T). Epithelium was removed from the corneas of rats with a BD Micro-Sharp, and wounded corneas were dyed with a 1% fluorescein solution. The corneal wounds were monitored using a fundus camera TRC-50X equipped with a digital camera. The corneal wound of rats instilled with saline was approximately 10% healing at 12 h, and approximately 65% healing at 24 h after corneal epithelial abrasion. The corneal wounds of rats instilled with saline showed almost complete healing by 36 h after corneal epithelial abrasion. On the other hand, the corneal healing rate of rats instilled with sericin solution was higher than that of rats instilled with saline, and the corneal healing rate constant increased with increasing sericin concentration. In addition, the adhesion and proliferation of HCE-T cells treated with 0.01-0.5% sericin solutions were enhanced, reaching a maximum at treatments with 0.2 and 0.1% sericin solutions, respectively. The present study demonstrates that the instillation of sericin solution has a potent effect in promoting wound healing and wound-size reduction in rats, probably caused by increasing cell movement and proliferation. PMID:19420767

  1. The Relationship between Corvis ST Tonometry Measured Corneal Parameters and Intraocular Pressure, Corneal Thickness and Corneal Curvature

    PubMed Central

    Asaoka, Ryo; Nakakura, Shunsuke; Tabuchi, Hitoshi; Murata, Hiroshi; Nakao, Yoshitaka; Ihara, Noriko; Rimayanti, Ulfah; Aihara, Makoto; Kiuchi, Yoshiaki

    2015-01-01

    The purpose of the study was to investigate the correlation between Corneal Visualization Scheimpflug Technology (Corvis ST tonometry: CST) parameters and various other ocular parameters, including intraocular pressure (IOP) with Goldmann applanation tonometry. IOP with Goldmann applanation tonometry (IOP-G), central corneal thickness (CCT), axial length (AL), corneal curvature, and CST parameters were measured in 94 eyes of 94 normal subjects. The relationship between ten CST parameters against age, gender, IOP-G, AL, CST-determined CCT and average corneal curvature was investigated using linear modeling. In addition, the relationship between IOP-G versus CST-determined CCT, AL, and other CST parameters was also investigated using linear modeling. Linear modeling showed that the CST measurement ‘A time-1’ is dependent on IOP-G, age, AL, and average corneal curvature; ‘A length-1’ depends on age and average corneal curvature; ‘A velocity-1’ depends on IOP-G and AL; ‘A time-2’ depends on IOP-G, age, and AL; ‘A length-2’ depends on CCT; ‘A velocity-2’ depends on IOP-G, age, AL, CCT, and average corneal curvature; ‘peak distance’ depends on gender; ‘maximum deformation amplitude’ depends on IOP-G, age, and AL. In the optimal model for IOP-G, A time-1, A velocity-1, and highest concavity curvature, but not CCT, were selected as the most important explanatory variables. In conclusion, many CST parameters were not significantly related to CCT, but IOP usually was a significant predictor, suggesting that an adjustment should be made to improve their usefulness for clinical investigations. It was also suggested CST parameters were more influential for IOP-G than CCT and average corneal curvature. PMID:26485129

  2. Cysticercosis in laboratory rabbits.

    PubMed

    Owiny, J R

    2001-03-01

    There are no data on the current incidence of Taenia pisiformis in laboratory rabbits. Two cases of cysticercosis most likely due to T. pisiformis in laboratory rabbits (intermediate host) are presented. Both rabbits had no contact with dogs (final host); their caretakers did not work with dogs, and these caretakers changed into facility scrubs and wore gloves when working with the rabbits. Rabbit 1 may have been infected after being fed hay at our facility. In light of the life cycle of the parasite and the history of rabbit 2, it potentially could have been infected prior to arrival at our facility. There have been only three cases of tapeworm cysts in rabbits in our facility (average daily census, 250) during the last 10 years (incidence, < 1%). This report indicates that although cysticercosis is rare in laboratory rabbits, one should always be aware of such incidental findings. Although it may not produce overt illness in the rabbit, hepatic migration could adversely affect the outcome of some experimental procedures PMID:11300689

  3. Clear Corneal Incision in Cataract Surgery

    PubMed Central

    Al Mahmood, Ammar M.; Al-Swailem, Samar A.; Behrens, Ashley

    2014-01-01

    Since the introduction of sutureless clear corneal cataract incisions, the procedure has gained increasing popularity worldwide because it offers several advantages over the traditional sutured scleral tunnels and limbal incisions. Some of these benefits include lack of conjunctival trauma, less discomfort and bleeding, absence of suture-induced astigmatism, and faster visual rehabilitation. However, an increasing incidence of postoperative endophthalmitis after clear corneal cataract surgery has been reported. Different authors have shown a significant increase up to 15-fold in the incidence of endophthalmitis following clear corneal incision compared to scleral tunnels. The aim of this report is to review the advantages and disadvantages of clear corneal incisions in cataract surgery, emphasizing on wound construction recommendations based on published literature. PMID:24669142

  4. Clear corneal incision in cataract surgery.

    PubMed

    Al Mahmood, Ammar M; Al-Swailem, Samar A; Behrens, Ashley

    2014-01-01

    Since the introduction of sutureless clear corneal cataract incisions, the procedure has gained increasing popularity worldwide because it offers several advantages over the traditional sutured scleral tunnels and limbal incisions. Some of these benefits include lack of conjunctival trauma, less discomfort and bleeding, absence of suture-induced astigmatism, and faster visual rehabilitation. However, an increasing incidence of postoperative endophthalmitis after clear corneal cataract surgery has been reported. Different authors have shown a significant increase up to 15-fold in the incidence of endophthalmitis following clear corneal incision compared to scleral tunnels. The aim of this report is to review the advantages and disadvantages of clear corneal incisions in cataract surgery, emphasizing on wound construction recommendations based on published literature. PMID:24669142

  5. Fuchs endothelial corneal dystrophy: current perspectives

    PubMed Central

    Vedana, Gustavo; Villarreal, Guadalupe; Jun, Albert S

    2016-01-01

    Fuchs endothelial corneal dystrophy (FECD) is the most common corneal dystrophy and frequently results in vision loss. Hallmarks of the disease include loss of corneal endothelial cells and formation of excrescences of Descemet’s membrane. Later stages involve all layers of the cornea. Impairment of endothelial barrier and pump function and cell death from oxidative and unfolded protein stress contribute to disease progression. The genetic basis of FECD includes numerous genes and chromosomal loci, although alterations in the transcription factor 4 gene are associated with the majority of cases. Definitive treatment of FECD is corneal transplantation. In this paper, we highlight advances that have been made in understanding FECD’s clinical features, pathophysiology, and genetics. We also discuss recent advances in endothelial keratoplasty and potential future treatments. PMID:26937169

  6. The genetics of Fuchs′ corneal dystrophy

    PubMed Central

    Iliff, Benjamin W; Riazuddin, S Amer; Gottsch, John D

    2013-01-01

    Fuchs′ corneal dystrophy (FCD) is a common late-onset genetic disorder of the corneal endothelium. It causes loss of endothelial cell density and excrescences in the Descemet membrane, eventually progressing to corneal edema, necessitating corneal transplantation. The genetic basis of FCD is complex and heterogeneous, demonstrating variable expressivity and incomplete penetrance. To date, three causal genes, ZEB1, SLC4A11 and LOXHD1, have been identified, representing a small proportion of the total genetic load of FCD. An additional four loci have been localized, including a region on chromosome 18 that is potentially responsible for a large proportion of all FCD cases. The elucidation of the causal genes underlying these loci will begin to clarify the pathogenesis of FCD and pave the way for the emergence of nonsurgical treatments. PMID:23585771

  7. Surgical compensation of presbyopia with corneal inlays.

    PubMed

    Konstantopoulos, Aris; Mehta, Jodhbir S

    2015-05-01

    Presbyopia, the physiological change in near vision that develops with ageing, gradually affects individuals older than 40 years and is a growing cause of visual disability due to ageing demographics of the global population. The routine use of computers and 'smartphones', combined with the affluence of the 'baby boomers' generation has set high standards for near vision correction. Corneal inlays are a relatively new treatment modality that is effective at compensating for presbyopia. The dimensions of these devices vary from 2 to 3.8 mm in diameter and 5 to 32 μm in thickness. They are implanted in the anterior corneal stroma of the non-dominant eye, most commonly, in a femtosecond laser created corneal pocket. They improve near vision by increasing the depth of focus, creating a hyper-prolate region of increased central cornea power or providing a refractive add power. This article reviews the literature on the efficacy and safety of corneal inlays. PMID:25652889

  8. Genetics Home Reference: congenital stromal corneal dystrophy

    MedlinePlus

    ... of decorin. This abnormal protein interferes with the organization of collagen fibrils in the cornea. As poorly arranged collagen fibrils accumulate, the cornea becomes cloudy. These corneal changes lead to reduced visual acuity and related eye ...

  9. Corneal Biomechanics Determination in Healthy Myopic Subjects

    PubMed Central

    Qiu, Kunliang; Lu, Xuehui; Zhang, Riping; Wang, Geng

    2016-01-01

    Purpose. To determine the corneal biomechanical properties by using the Ocular Response Analyzer™ and to investigate potential factors associated with the corneal biomechanics in healthy myopic subjects. Methods. 135 eyes from 135 healthy myopic subjects were included in this cross-sectional observational study. Cornea hysteresis (CH), corneal resistance factor (CRF), cornea-compensated intraocular pressure (IOPcc), and Goldmann-correlated intraocular pressure (IOPg) were determined with the Reichert Ocular Response Analyzer (ORA). Univariate and multivariate regression analyses were performed to investigate factors associated with corneal biomechanics. Results. The mean CH and CRF were 9.82 ± 1.34 mmHg and 9.64 ± 1.57 mmHg, respectively. In univariate regression analysis, CH was significantly correlated with axial length, refraction, central corneal thickness (CCT), and IOPg (r = −0.27, 0.23, 0.45, and 0.21, resp.; all with p ≤ 0.015), but not with corneal curvature or age; CRF was significantly correlated with CCT and IOPg (r = 0.52 and 0.70, resp.; all with p < 0.001), but not with axial length/refraction, corneal curvature, or age. In multivariate regression analysis, axial length, IOPcc, and CCT were found to be independently associated with CH, while CCT and IOPg were associated with CRF. Conclusions. Both CH and CRF were positively correlated with CCT. Lower CH but not CRF was associated with increasing degree of myopia. Evaluation of corneal biomechanical properties should take CCT and myopic status into consideration. PMID:27525109

  10. Isolation and transplantation of corneal endothelial cell-like cells derived from in-vitro-differentiated human embryonic stem cells.

    PubMed

    Zhang, Kai; Pang, Kunpeng; Wu, Xinyi

    2014-06-15

    The maintenance of corneal dehydration and transparency depends on barrier and pump functions of corneal endothelial cells (CECs). The human CECs have no proliferation capacity in vivo and the ability to divide in vitro under culture conditions is dramatically limited. Thus, the acquisition of massive cells analogous to normal human CECs is extremely necessary whether from the perspective of cellular basic research or from clinical applications. Here we report the derivation of CEC-like cells from human embryonic stem cells (hESCs) through the periocular mesenchymal precursor (POMP) phase. Using the transwell coculture system of hESCs with differentiated human corneal stromal cells, we induced hESCs to differentiate into POMPs. Then, CEC-like cells were derived from POMPs with lens epithelial cell-conditioned medium. Within 1 week, CEC-like cells that expressed the corneal endothelium (CE) differentiation marker N-cadherin and transcription factors FoxC1 and Pitx2 were detectable. Fluorescence-activated cell sorting (FACS)-based isolation of the N-cadherin/vimentin dual-positive population enriches for CEC-like cells. The isolated CEC-like cells were labeled with carboxyfluorescein diacetate, succinimidyl ester (CFDA SE) and seeded onto posterior acellular porcine corneal matrix lamellae to construct the CEC-like cell sheets. Pump function parameters of the CEC-like cell sheets approximated those of human donor corneas. Importantly, when the CEC-like cell sheets were transplanted into the eyes of rabbit CE dysfunction models, the corneal transparency was restored gradually. In conclusion, CEC-like cells derived from hESCs displayed characteristics of native human CECs. This renewable source of human CECs offers massive cells for further studies of human CEC biological characteristics and potential applications of replacement therapies as substitution for donor CECs in the future. PMID:24499373