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  • 1.
    Bourghardt Peebo, Beatrice
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    An in Vivo Method for Visualizing Flow Dynamics of Cells within Corneal Lymphatics2013In: Lymphatic Research and Biology, ISSN 1539-6851, E-ISSN 1557-8585, Vol. 11, no 2, 93-100 p.Article in journal (Refereed)
    Abstract [en]

    Background: Monitoring the trafficking of specific cell populations within lymphatics could improve our understanding of processes such as transplant rejection and cancer metastasis. Current methods, however, lack appropriate image resolution for single-cell analysis or are incompatible with in vivo and longitudinal monitoring of lymphatics in their native state. We therefore sought to achieve high-resolution live imaging of the dynamic behavior of cells within lymph vessels in the rat cornea.

    Methods/Results: Inflammatory angiogenesis was induced by suture placement in corneas of Wistar rats. Pre- and up to 3 weeks post-induction, corneas were noninvasively examined by laser-scanning in vivo corneal confocal microscopy (IVCM) using only endogenous contrast. Lymph vessels and the cells harbored therein were documented by still images, real-time video, and 3D confocal stack reconstruction of live tissue. In vivo, conjunctival and corneal lymphatics were morphologically distinct, those with corneal location being one-quarter the diameter of those in the conjunctiva (p<0.001). Cells were recruited to initially empty pre-existing lymph vessels during the first day of inflammation and maintained a dense occupation of vessels for up to 7 days. A diverse population of cells (diameter range: 1.5–27.5 μm) with varying morphology was observed, and exhibited variable flow patterns and were transported singly and in clusters of at least 2–9 adherent cells.

    Conclusions: The in vivo microscopic technique presented enables lymph vessels and cell trafficking to be studied in high resolution in a minimally-perturbed physiologic milieu.

  • 2.
    Bourghardt Peebo, Beatrice
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Letter: In vivo confocal microscopy visualization of presumed lymph vessels in a case of corneal transplant rejection2011In: Clinical and Experimental Ophthalmology, ISSN 1442-6404, E-ISSN 1442-9071, Vol. 39, no 8, 832-834 p.Article in journal (Other academic)
    Abstract [en]

    n/a

  • 3.
    Bourghardt Peebo, Beatrice
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Transient Anterior Corneal Deposits in a Human Immunodeficiency Virus-Positive Patient2010In: CORNEA, ISSN 0277-3740, Vol. 29, no 11, 1323-1327 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: To report findings of pigmented anterior corneal deposits in a human immunodeficiency virus-positive patient. Methods: Case report. A 49-year-old human immunodeficiency virus-positive patient was examined after the appearance of pigmented corneal deposits. Slit-lamp biomicroscopy, fundus photography, and laser-scanning in vivo confocal microscopy were performed to visually document the ocular condition. Results: The patient had a history of Mycobacterium avium infection and was suspected to have recovery uveitis from a cytomegalovirus infection. Small, rounded, light brown-colored deposits were distributed across the anterior cornea from limbus to limbus, bilaterally. In vivo confocal microscopy revealed the deposits to be confined to the basal epithelium and Bowman layer, whereas the posterior stroma, Descemet membrane, and the endothelium appeared normal. Systemic steroid treatment was administered, and 2 weeks later, the deposits had vanished on slit-lamp examination, whereas remnants were observed at the microscopic level. Conclusions: The deposits were unusual for their anterior corneal location and pancorneal distribution. The response to systemic steroid treatment remains unexplained and illustrates the complexity of the underlying conditions, their treatment, and the associated pathways of ocular manifestation.

  • 4.
    Bourghardt Peebo, Beatrice
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Traneus-Rockert, Catharina
    Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Cellular level characterization of capillary regression in inflammatory angiogenesis using an in vivo corneal model2011In: Angiogenesis, ISSN 0969-6970, E-ISSN 1573-7209, Vol. 14, no 3, 393-405 p.Article in journal (Refereed)
    Abstract [en]

    In this study, we introduce a technique for repeated, microscopic observation of single regressing capillaries in vivo in inflamed murine corneas. Natural capillary regression was initiated by removal of inflammatory stimulus during an active pro-angiogenic phase, while the additional impact of anti-angiogenic treatment with triamcinolone or bevazicumab was investigated. Capillaries regressed naturally within 1 week and treatments did not further enhance the natural regression. Morphologically, early-phase regression was characterized by significant lumen narrowing and a significant reduction in CD11b+ myeloid cell infiltration of the extracellular matrix. By 1 week, vascular remodeling occurred concomitant with CD11b+CD68+KiM2R+ mature macrophage localization on capillary walls. Empty conduits without blood flow, positive for collagen IV and devoid of vascular endothelium and pericytes, were apparent in vivo and by 3 weeks were more numerous than perfused capillaries. By 3 weeks, macrophages aggregated around remaining perfused capillaries and were observed in apposition with degrading capillary segments. Abrupt termination of capillary sprouting in our regression model further revealed vascular endothelial abandonment of sprout tips and perfused capillary loop formation within a single angiogenic sprout, possibly as an intussusceptive response to cessation of the stimulus. Finally, we observed lumen constriction and macrophage localization on capillary walls in vivo in a clinical case of corneal capillary regression that paralleled findings in our murine model.

  • 5.
    Bourghardt Peebo, Beatrice
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Traneus-Rockert, Catharina
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Lagali, Neil
    Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences.
    Cellular-Level Characterization of Lymph Vessels in Live, Unlabeled Corneas by In Vivo Confocal Microscopy2010In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 51, no 2, 830-835 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To determine whether in vivo confocal microscopy (IVCM) of the cornea can be used for the label-free detection and monitoring of lymph vessels in live corneas.

    METHODS. Parallel corneal hemangiogenesis and lymphangiogenesis was induced by the placement of a single suture in one cornea of male Wistar rats. Fourteen days after suture placement and under general anesthesia, laser-scanning IVCM was performed in the vascularized region. Corneas were subsequently excised for flat-mount double immunofluorescence with a pan-endothelial marker (PECAM-1/CD31) and a lymphatic endothelial specific marker (LYVE-1). Using the suture area and prominent blood vessels as points of reference, the identical microscopic region was located in both fluorescent and archived in vivo images. Additionally, vessel diameter, lumen contrast, and cell diameter and velocity within vessels were quantified from in vivo images.

    RESULTS. Comparison of identical corneal regions in fluorescence and in vivo revealed prominent CD31(+)/LYVE-1(3+) lymph vessels that were visible in vivo. In vivo, corneal lymph vessels were located in the vascularized area in the same focal plane as blood vessels but had a darker lumen (P andlt; 0.001) sparsely populated by highly reflective cells with diameters similar to those of leukocytes in blood vessels (P = 0.61). Cell velocity in lymph vessels was significantly reduced compared with blood particle velocity (P andlt; 0.001). Morphologic characteristics enabled subsequent identification of corneal lymphatics in live, vascularized rat corneas before immunofluorescence labeling.

    CONCLUSIONS. IVCM enabled the nondestructive, label-free, in vivo detection of corneal lymphatics. IVCM provides the possibility of observing lymphatic activity in the same live corneas longitudinally and, as a clinical instrument, of monitoring corneal lymphatics in live human subjects.

  • 6.
    Bourghardt Peebo, Beatrice
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Traneus-Rockert, Catharina
    Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Time-Lapse In Vivo Imaging of Corneal Angiogenesis: The Role of Inflammatory Cells in Capillary Sprouting2011In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 52, no 6, 3060-3068 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To elucidate the temporal sequence of events leading to new capillary sprouting in inflammatory corneal angiogenesis.

    METHODS. Angiogenesis was induced by corneal suture placement in Wistar rats. The inflamed region was examined by time-lapse in vivo confocal microscopy for up to 7 days. At 6 and 12 hours and 1, 2, 4, and 7 days, corneas were excised for flat mount immunofluorescence with primary antibodies for CD31, CD34, CD45, CD11b, CD11c, Ki-M2R, NG2, and alpha-SMA. From days 0 to 4, the in vivo extravasation and expansion characteristics of single limbal vessels were quantified.

    RESULTS. Starting hours after induction and peaking at day 1, CD45(+)CD11b(+) myeloid cells extravasated from limbal vessels and formed endothelium-free tunnels within the stroma en route to the inflammatory stimulus. Limbal vessel diameter tripled on days 2 to 3 as vascular buds emerged and transformed into perfused capillary sprouts less than 1 day later. A subset of spindle-shaped CD11b(+) myeloid-lineage cells, but not dendritic cells or mature macrophages, appeared to directly facilitate further capillary sprout growth. These cells incorporated into vascular endothelium near the sprout tip, co-expressing endothelial marker CD31. Sprouts had perfusion characteristics distinct from feeder vessels and many sprout tips were open-ended.

    CONCLUSIONS. Time-lapse in vivo corneal confocal microscopy can be used to track a temporal sequence of events in corneal angiogenesis. The technique has revealed potential roles for myeloid cells in promoting vessel sprouting in an inflammatory corneal setting.

  • 7.
    Bourghardt Peebo, Beatrice
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL.
    Gan, Lisha
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Knutsen Holmqvist, Annica
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Rearden, Ann
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL.
    Expression of the focal adhesion protein PINCH in normal and alkali-injured corneas and the role of PMNs2007In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 85, no 4, 395-400 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate the role of particularly interesting new cysteine-histidine-rich protein (PINCH) in corneal wound healing and early neovascularization and to assess the influence of granulocytes. Methods: A standardized corneal alkali wound was inflicted under general anaesthesia to the right eye of 14 New Zealand White rabbits. Seven of the rabbits received i.v. 5 mg/kg fucoidin every 2 hours to prevent granulocytes from entering the wound area. After 36 hours, the rabbits were killed, the corneas excised, fixed in 4% formaldehyde and embedded in paraffin. The sections were double-stained with antibodies against PINCH and with haematoxylin. Results: In the normal cornea and limbus, PINCH was weakly expressed in the corneal epithelium and in a wedge of the conjunctival stroma. In the wounded corneas, PINCH expression was seen in the frontline of repopulating endothelial and epithelial cells, and in active keratocytes. The vascular endothelium and the granulocytes expressed PINCH, as did the conjunctival epithelium. In the fucoidin-treated rabbits, PINCH expression was markedly reduced. The vascular endothelial cells and the few granulocytes did not express PINCH in these rabbits. Conclusions: PINCH is only slightly expressed in the normal cornea. A corneal wound induces PINCH expression in the repopulating cells, in the vascular endothelial cells of the limbus, in the limbal epithelium and in the granulocytes. Exclusion of granulocytes reduces expression of PINCH and there is no expression at all in the vascular endothelium. © 2007 The Authors Journal compilation 2007 Acta Ophthalmol Scand.

  • 8.
    Bourghardt Peebo, Beatrice
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL.
    Koulikovska, Marina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL.
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL.
    The suppression of early angiogenic markers by the antiangiogenic aptamer Macugen R is dose dependent2007In: European Association for Vision and Eye Research,2007, 2007Conference paper (Other academic)
  • 9.
    Buznyk, Oleksiy
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. National Academic Medical Science Ukraine, Ukraine.
    Pasyechnikova, Nataliya
    National Academic Medical Science Ukraine, Ukraine.
    Islam, Mohammad Mirazul
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Iakymenko, Stanislav
    National Academic Medical Science Ukraine, Ukraine.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Bioengineered Corneas Grafted as Alternatives to Human Donor Corneas in Three High-Risk Patients2015In: Clinical and Translational Science, ISSN 1752-8054, E-ISSN 1752-8062, Vol. 8, no 5, 558-562 p.Article in journal (Refereed)
    Abstract [en]

    Corneas with severe pathologies have a high risk of rejection when conventionally grafted with human donor tissues. In this early observational study, we grafted bioengineered corneal implants made from recombinant human collagen and synthetic phosphorylcholine polymer into three patients for whom donor cornea transplantation carried a high risk of transplant failure. These patients suffered from corneal ulcers and recurrent erosions preoperatively. The implants provided relief from pain and discomfort, restored corneal integrity by promoting endogenous regeneration of corneal tissues, and improved vision in two of three patients. Such implants could in the future be alternatives to donor corneas for high-risk patients, and therefore, merits further testing in a clinical trial.

  • 10. Claesson, M
    et al.
    Armitage, W J
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Stenevi, U
    Visual outcome in corneal grafts: a preliminary analysis of the Swedish Corneal Transplant Register2002In: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079, Vol. 86, 174-180 p.Article in journal (Refereed)
  • 11.
    Eden, U
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Linköping University, Faculty of Health Sciences.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH. Linköping University, Faculty of Health Sciences.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Pathologic epithelial and anterior corneal nerve morphology in congenital aniridic keratopathy in ACTA OPHTHALMOLOGICA, vol 88, issue , pp 52-522010In: ACTA OPHTHALMOLOGICA, Blackwell Publishing Ltd , 2010, Vol. 88, 52-52 p.Conference paper (Refereed)
    Abstract [en]

    n/a

  • 12.
    Eden, Ulla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Danyali, Reza
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Pathologic Epithelial and Anterior Corneal Nerve Morphology in Early-Stage Congenital Aniridic Keratopathy2012In: Ophthalmology (Rochester, Minn.), ISSN 0161-6420, E-ISSN 1549-4713, Vol. 119, no 9, 1803-1810 p.Article in journal (Refereed)
    Abstract [en]

    Objective: To document the clinical and morphologic corneal findings in the early stages of congenital aniridic keratopathy in Swedish families. less thanbrgreater than less thanbrgreater thanDesign: Prospective, observational, comparative case series. less thanbrgreater than less thanbrgreater thanParticipants: A total of 16 eyes of 16 subjects with congenital aniridic keratopathy and a clear central cornea, and 6 eyes from 6 healthy controls (unaffected relatives). Nine of the 16 eyes with aniridia came from 5 families with a documented familial history of aniridia. less thanbrgreater than less thanbrgreater thanMethods: Detailed ophthalmic examinations included best spectacle-corrected visual acuity (BSCVA), tear film production, tear break-up time (BUT), corneal touch sensitivity, intraocular pressure measurement, ultrasound pachymetry, slit-lamp biomicroscopy, and laser scanning in vivo confocal microscopy (IVCM). less thanbrgreater than less thanbrgreater thanMain Outcome Measures: Confirmed stage of aniridic keratopathy, clinical parameters of cornea and tear film (visual acuity, sensitivity, corneal thickness, tear production, and BUT), and the morphologic status of corneal epithelium, sub-basal nerves, and limbal palisades of Vogt. less thanbrgreater than less thanbrgreater thanResults: In early-stage aniridic keratopathy, BSCVA and tear BUT were reduced relative to controls (P andlt; 0.001 for both), and corneal thickness was increased (P = 0.01). Inflammatory dendritic cells were present in the central epithelium in aniridia, with significantly increased density relative to controls (P = 0.001). Discrete focal opacities in the basal epithelial region were present in 5 of 11 aniridia cases with an otherwise clear cornea. Opacities were associated with dendritic cells and harbored structures presumed to be goblet cells. Sub-basal nerves were extremely dense in 3 aniridia cases, and a prominent whorl pattern of nerves and epithelial cells was observed in 1 case. Normal limbal palisade morphology was absent in aniridia but present in controls. less thanbrgreater than less thanbrgreater thanConclusions: Early-stage aniridic keratopathy is characterized by the development of focal opacities in the basal epithelium, altered sub-basal nerves, infiltration of the central epithelium by dendritic cells, tear film instability, and increased corneal thickness and degradation of limbal palisade architecture. These findings may help to elucidate the pathogenesis of aniridic keratopathy. less thanbrgreater than less thanbrgreater thanFinancial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

  • 13.
    Edén, Ulla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Dellby, Anette
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Utheim, Tor P.
    Oslo University Hospital, Norway Harvard University, MA 02114 USA .
    Riise, Ruth
    Innland Hospital, Norway .
    Chen, Xiangjun
    Synslaser Kirurgi AS, Norway .
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Letter: Cataract development in Norwegian patients with congenital aniridia2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 2, E165-E167 p.Article in journal (Other academic)
    Abstract [en]

    n/a

  • 14.
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL.
    An update on the synthetic collagenous artificial cornea2007In: European Association for Vision and Eye Research,2007, 2007, 4315-4315 p.Conference paper (Other academic)
  • 15.
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL.
    Cornearelaterade sjukdomar och förändringar2004Report (Other academic)
  • 16.
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Excimerlasern - Ett instrument som revolutionerat hornhinnekirurgi2003In: Incitament, ISSN 1103-503X, 43-46 p.Article in journal (Other (popular science, discussion, etc.))
  • 17.
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL.
    Laser eye surgery for the correction of refractive errors2007Report (Other academic)
  • 18.
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL.
    Operation vid brytningsfel i ögat2007Report (Other academic)
  • 19.
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Phototherapeutic keratectomy: 12 years of experience2003In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 81, no 1, 19-32 p.Article in journal (Refereed)
    Abstract [en]

    Background: Phototherapeutic keratectomy (PTK) has been employed as a surgical tool to treat corneal disease for more than 10 years. The laser has made it possible to remove superficial corneal opacities and thereby restore vision. The 193 nm ultraviolet light separates molecules and splits molecules in biological tissue, thereby ablating it. About 0.25 ╡m of tissue is ablated by each pulse. The development of the excimer laser technique has been fast. It has principally focused on refractive surgery but has also benefited PTK. Corneal dystrophies: The ability to delay or postpone corneal grafting in superficial corneal dystrophies represents a very important achievement. Map-dot-fingerprint dystrophy or basal membrane dystrophy is a common indication for PTK. Other dystrophies such as Meesman's, Reis-Bⁿckler's, Thiel-Benke's, granular, macular, lattice and Schnyder's can be treated, although with differing degrees of success and varying rates of recurrence. Subepithelial scarring in Fuchs' dystrophy has been ablated. Other trials have involved the removal of substantial parts of the stroma in order to reduce the load on the endothelium. Recurrent dystrophic changes can likewise be removed from corneal grafts and thus prevent the need for regrafting. Recurrent erosions: Laser treatment has made it possible to manage wound-healing problems better after recurrent erosions. Recurrent erosions are the most common indications for PTK: several studies show good and persistent effects with this type of treatment. Persistent epithetial defects of various origins, among them corneal ulcers resulting from allergic disease, can likewise be treated. Scar tissue: Scars after surgery such as pterygeum excision can be removed. Smooth muscle actin containing fibroblasts in old scars should be given special consideration in PTK. Excimer laser surgery can be successfully combined with conventional surgery to remove excessive scar tissue, Salzmann's nodules and very flaky and coarse band keratopathy. Irregular corneal surfaces following ulcers and injuries pose problems that have so far proved difficult to overcome. Thinning is often seen after bacterial corneal ulcers or after herpes simplex keratitis. A rough or uneven surface can be made smoother by using modulators during treatment by casting a new surface under a hard contact lens (PALM technique), a surface that is then projected into the stroma by laser ablation. Modern techniques linking the excimer laser with computerized corneal topography and wavefront analysis promise to further improve the smoothing capacities of lasers and to increase the quality of optical results. Complications: The most feared complication of PTK is the postoperative infection. These are rare. Haze is usually not prominent but scar tissue formation of a more persistent type has been noted after laser surgery in eyes with pre-existing surgical scars. Keratectasia has been described after PTK. Failure due to deep opacities or a surface that is too uneven is a more common frustration. This paper reviews advances in excimer laser treatment of corneal disease.

  • 20.
    Fagerholm, Per
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Claesson, Margareta
    Claesson, Margareta
    Stenevi, Ulf
    Stenevi, Ulf
    Växande väntelista för kornealtransplantation2003In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 99, 385-387 p.Article in journal (Other academic)
  • 21.
    Fagerholm, Per
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL.
    Dellby, Anette
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology.
    Bäckman, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology VHN.
    Inherited corneal opacifications with an unusual distribution2007In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 85, no 1, 103-105 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: To describe corneal opacities of a new type and distribution in a small family. Methods: Family members were interviewed and examined to establish a pedigree and to detect any corneal abnormalities. Results: Two family members presented with corneal opacities. Both had, in the very peripheral cornea, flat, greyish, rounded opacities, 20-200μm in diameter, on the Descemet's membrane. In addition, the mother had the same type of opacities over the central cornea just inside the Bowman's layer. The remaining parts of the corneas were clear. Vision was unaffected and the opacities caused no discomfort. There was no other corneal pathology. The subjects' general health was good. Conclusions: To our knowledge, these types and distribution of corneal opacities have not been described previously. Although the mode of inheritance at this point is uncertain, we believe the changes are of a dystrophic nature. © 2007 Acta Ophthalmol Scand.

  • 22.
    Fagerholm, Per
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL.
    Eckerlund, Ingemar
    Statens beredning för medicinsk utvärdering Stockholm.
    Refractive surgery. An Allert report from SBU2008In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, no 26-27, 1926-1928 p.Article in journal (Refereed)
  • 23.
    Fagerholm, Per
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Gan, Lisha
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology .
    Palmblad, J
    Expression of VEGF and its receptor VEGFR-2/flk-1 following rabbit corneal alkali burn in the presence and absence of granulocytes2002In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 43, 4210- p.Conference paper (Other academic)
  • 24.
    Fagerholm, Per
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL.
    Gan, Lisha
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology.
    Palmblad, Jan
    Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 in the regulation of corneal neovascularization and wound healing2004In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 82, no 5, 557-563 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: To study the change in expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 in the rabbit cornea and limbus following a penetrating, central corneal alkali burn. The influence of different cells on VEGF and VEGFR-2 expression was studied by excluding granulocytes from the wound area. Methods: Fourteen New Zealand white rabbits were subjected to a penetrating, 5-mm diameter, central corneal alkali burn in one eye under general anaesthesia. Seven of the rabbits were given injections of fucoidin for 36 hours. The rabbits were killed after 36 hours and the corneas were excised with a sclera rim and prepared for immunohistochemistry. Results: Both VEGF and VEGFR-2 are strongly expressed in the frontline of repopulating epithetial, stromal and endothelial cells during wound healing, irrespective of granulocyte presence. Vascular endothelial cells express VEGF strongly after injury, but only in the presence of granulocytes. Conclusion: Corneal neovascularization requires the presence of granulocytes to stimulate vascular endothelial cells. During wound healing in this area, VEGF is a factor that stimulates proliferation and migration and that is not influenced by granulocytes.

  • 25.
    Fagerholm, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Carlsson, David J.
    National Research Council of Canada, Ottawa, Ontario; University of Ottawa Eye Institute, Ontario, Canada.
    Merrett, Kimberley
    University of Ottawa Eye Institute, Ontario, Canada.
    Griffith, May
    University of Ottawa Eye Institute, Ontario, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Canada.
    Corrigendum to “Corneal Regeneration Following Implantation of a Biomimetic Tissue-Engineered Substitute”  [vol 2, Issue 2, pg 162-164, 2009]2014In: Clinical and Translational Science, ISSN 1752-8054, E-ISSN 1752-8062, Vol. 7, no 4, 347-347 p.Article in journal (Other academic)
    Abstract [en]

    n/a

  • 26.
    Fagerholm, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Ong, Jeb A.
    Maisonneuve Rosemont Hospital, Montreal, Canada .
    Merrett, Kimberley
    Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping. Ottawa Hospital Research Institute, Canada.
    Jackson, W. Bruce
    Ottawa Hospital Research Institute, Canada .
    Polarek, James W.
    FibroGen Inc, San Francisco, CA, USA.
    Suuronen, Erik J.
    University of Ottawa Heart Institute, Canada .
    Liu, Yuwen
    CooperVision Inc, Pleasanton, CA, USA.
    Brunette, Isabelle
    Maisonneuve Rosemont Hospital, Montreal, Canada .
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Stable corneal regeneration four years after implantation of a cell-free recombinant human collagen scaffold2014In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 35, no 8, 2420-2427 p.Article in journal (Refereed)
    Abstract [en]

    We developed cell-free implants, comprising carbodiimide crosslinked recombinant human collagen (RHC), to enable corneal regeneration by endogenous cell recruitment, to address the worldwide shortage of donor corneas. Patients were grafted with RHC implants. Over four years, the regenerated neo-corneas were stably integrated without rejection, without the long immunosuppression regime needed by donor cornea patients. There was no recruitment of inflammatory dendritic cells into the implant area, whereas, even with immunosuppression, donor cornea recipients showed dendritic cell migration into the central cornea and a rejection episode was observed. Regeneration as evidenced by continued nerve and stromal cell repopulation occurred over the four years to approximate the micro-architecture of healthy corneas. Histopathology of a regenerated, clear cornea from a regrafted patient showed normal corneal architecture. Donor human cornea grafted eyes had abnormally tortuous nerves and stromal cell death was found. Implanted patients had a 4-year average corrected visual acuity of 20/54 and gained more than 5 Snellen lines of vision on an eye chart. The visual acuity can be improved with more robust materials for better shape retention. Nevertheless, these RHC implants can achieve stable regeneration and therefore, represent a potentially safe alternative to donor organ transplantation.

  • 27.
    Fagerholm, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Lagali, Neil S
    Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences.
    Carlsson, David J
    Natl Res Council Canada, Ottawa, ON K1A 0R6, Canada.
    Merrett, Kimberley
    Univ Ottawa, Inst Eye, Ottawa, ON K1H 8L6, Canada.
    Griffith, May
    Univ Ottawa, Inst Eye, Ottawa, ON K1H 8L6, Canada.
    Corneal Regeneration Following Implantation of a Biomimetic Tissue-Engineered Substitute2009In: CTS-CLINICAL AND TRANSLATIONAL SCIENCE, ISSN 1752-8054, Vol. 2, no 2, 162-164 p.Article in journal (Refereed)
    Abstract [en]

    n/a

  • 28.
    Fagerholm, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Lagali, Neil S
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Merrett, Kimberley
    University of Ottawa Eye Institute.
    Jackson, W Bruce
    University of Ottawa Eye Institute.
    Munger, Rejean
    University of Ottawa Eye Institute.
    Liu, Yuwen
    CooperVision Inc, Pleasanton, USA .
    Polarek, James W
    FibroGen Inc, San Francisco.
    Söderqvist, Monica
    Synsam Opticians, Linköping.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences.
    A biosynthetic alternative to human donor tissue for inducing corneal regeneration: 24-month follow-up of a phase 1 clinical study2010In: Science translational medicine, ISSN 1946-6234, Vol. 2, no 46, 46-61 p.Article in journal (Refereed)
    Abstract [en]

    Corneas from human donors are used to replace damaged tissue and treat corneal blindness, but there is a severe worldwide shortage of donor corneas. We conducted a phase 1 clinical study in which biosynthetic mimics of corneal extracellular matrix were implanted to replace the pathologic anterior cornea of 10 patients who had significant vision loss, with the aim of facilitating endogenous tissue regeneration without the use of human donor tissue. The biosynthetic implants remained stably integrated and avascular for 24 months after surgery, without the need for long-term use of the steroid immunosuppression that is required for traditional allotransplantation. Corneal reepithelialization occurred in all patients, although a delay in epithelial closure as a result of the overlying retaining sutures led to early, localized implant thinning and fibrosis in some patients. The tear film was restored, and stromal cells were recruited into the implant in all patients. Nerve regeneration was also observed and touch sensitivity was restored, both to an equal or to a greater degree than is seen with human donor tissue. Vision at 24 months improved from preoperative values in six patients. With further optimization, biosynthetic corneal implants could offer a safe and effective alternative to the implantation of human tissue to help address the current donor cornea shortage.

  • 29.
    Fagerholm, Per
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Linköping University, Faculty of Health Sciences.
    Molander, Nils
    Medocular, Malmö, Sweden.
    Podskochy, Alexander
    Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Linköping University, Faculty of Health Sciences.
    Sundelin, Staffan
    Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Linköping University, Faculty of Health Sciences.
    Epithelial ingrowth after LASIK treatment with scraping and phototherapeutic keratectomy2004In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 82, no 6, 707-713 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate the effect of phototherapeutic keratectomy (PTK) in combination with manual scraping when removing epithelial ingrowth under a LASIK flap.

    Material and Methods: Three patients, who had undergone several surgeries following LASIK in order to remove epithelial ingrowth that was threatening vision, were treated with a flap lift, manual abrasion and PTK. The PTK was performed on both the stromal and the flap side with the aim of eliminating the threat and improving vision. Two patients underwent primary surgery to remove epithelial ingrowth with manual abrasion and PTK. The influence on vision, topography and cell recurrences was evaluated.

    Results: Uncorrected visual acuity (UCVA) and best spectacle-corrected visual acuity (BSCVA) improved in four cases and remained good in the fifth case. The refraction did not change significantly. Topography disclosed changes in the irregular astigmatism, explaining the improved BSCVA. Central epithelial ingrowth did not recur, whereas peripheral ingrowth did. The peripheral ingrowth did not progress, except in case 1, where a cyst formed that required surgery.

    Conclusions: It is our belief that adding PTK to manual scraping improves the prognosis for eyes with epithelial ingrowth. It is mainly the central ingrowth that is positively affected. Improved adhesion between the stroma and the flap is one possible explanation.

  • 30.
    Gan, Lisha
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Leukocytes in the early events of corneal neovascularization2001In: Cornea, ISSN 0277-3740, E-ISSN 1536-4798, Vol. 20, 96-99 p.Article in journal (Refereed)
  • 31.
    Gan, Lisha
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology .
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Blalock, TD
    Schultz, GS
    Connective tissue growth factor (CTGF) in the alkali wounded corneas2002In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 43, 4207- p.Conference paper (Other academic)
  • 32.
    Gan, Lisha
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology.
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL.
    Palmblad, Jan
    Expression of basic fibroblast growth factor in rabbit corneal alkali wounds in the presence and absence of granulocytes2005In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 83, no 3, 374-378 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: To study the expression of basic fibroblast growth factor (bFGF) in the early phases of corneal wound healing in the presence or absence of granulocytes. Methods: A central penetrating corneal alkali wound was inflicted to one eye in each of 14 rabbits under general anaesthesia. Subsequently, seven of the rabbits were given fucoidin i.v. for 36 hours in order to block the selectins on the vascular endothelium, thus preventing blood granulocytes from entering the tissues. Then, corneas were prepared, stained for bFGF and evaluated by light microscopy. Results: Whereas normal corneal epithelium expressed bFGF weakly, conjunctival epithelium did so strongly, particularly the goblet cells. The corneal endothelium showed medium staining, while keratocytes and vascular endothelial cells did not consistently express bFGF. After 36 hours of wound healing, a marked upregulation of bFGF expression was observed in the corneal epithelial and endothelial cells, as well as in the keratocytes, that were migrating into the wound. No other changes were noted. None of these features were modulated when granulocyte emigration was prevented by fucoidin administration. Conclusions: The difference in bFGF expression between the corneal and conjunctival epithelium suggests a role for this growth factor in the barrier function at the limbus. Moreover, the specific presence of bFGF in cells migrating into the wound indicates the participation of bFGF in corneal wound healing. Expression of bFGF was independent of granulocytes. Copyright © Acta Ophthalmol Scand 2005.

  • 33.
    Gan, Lisha
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Hamberg-Nyström, Hélene
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Van Setten, Gysbert
    Cellular proliferation and leukocyte infiltration in the rabbit cornea after photorefractive keratectomy2001In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 79, no 5, 488-492 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: To map the proliferative activity of corneal cells during wound healing following photorefractive keratectomy (PRK) and to compare two markers for proliferation. Methods: PRK, 5- mm in diameter with a -6 D setting, was performed in one eye of 28 New Zealand White Rabbits. The rabbits were sacrificed at time points between 12 hours and three months after surgery. The treated and fellow corneas were fixed in 10% formaldehyde, paraffin embedded, and immunohistochemically stained for proliferate cell nuclear antigen (PCNA) and at one time point, 1 week, also for Ki-67. Results: Following initial sliding of the epithelial cells, the proliferative activity in the wound area starts in the leading edge (24 hours) and is spread towards the periphery. The proliferative activity peaks after one week and subsides during the following two weeks. Early (24 hours) proliferative activity is also seen in the limbal epithelium which peaks after three days. The keratocytes express PCNA in the peripheral stroma 48 hours after injury. They then also migrate to repopulate the stroma under the wound area. The expression period lasts 1 week and subsides the following week. Leukocytes are found in the wound as early as 12 hours after injury. The cells disappear around the time of epithelial wound closure, i.e. after 3 days. The two proliferative markers PCNA and KI 67 show a similar distribution after surgery. Conclusion: Epithelial proliferative activity starts earlier after injury, and is preceded by leukocyte presence in the wound. The PCNA expression starts later in the keratocytes but lasts somewhat longer (3 weeks). PCNA expression appears more efficient than Ki-67 to show proliferative activity of slow cycling cells in the cornea.

  • 34.
    Ganesh, Anuradha
    et al.
    Sultan Qaboos University.
    Pirouznia, Saeid
    Uddevalla Central Hospital.
    Ganguly, Shyam S
    Sultan Qaboos University.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Lithander, Joan
    Uddevalla Central Hospital.
    Consecutive exotropia after surgical treatment of childhood esotropia: a 40-year follow-up study2011In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 89, no 7, 691-695 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: To determine the incidence of consecutive exotropia (XT) following successful surgical correction of childhood esotropia (ET) and identify factors associated with its development. less thanbrgreater than less thanbrgreater thanMaterial and Methods: This is a retrospective study of 85 patients with ET, aged 2-24, who underwent strabismus surgery by a single surgeon between 1958 and 1969 in Sweden, until they were successfully aligned to ET within 10 prism dioptre, after primary or reoperation(s). The charts of these patients were reviewed, and data regarding age at onset of strabismus, surgery performed and outcome were recorded. The patients were recalled for a complete orthoptic examination in 2001-2003. less thanbrgreater than less thanbrgreater thanResults: The incidence of consecutive XT in this cohort was 21% (18/85). Patients who had undergone multiple surgeries had a higher risk of developing consecutive XT compared to those successfully aligned with one surgery (p = 0.00036). Restriction of adduction and convergence postoperatively was associated with a high risk of consecutive XT (p = 0.0437). The incidence of consecutive XT did not vary with the level of visual acuity in the operated eye (p = 0.6428). Age of onset, age at surgery and amount of surgery did not appear to influence the risk for developing consecutive XT (p andgt; 0.05). less thanbrgreater than less thanbrgreater thanConclusion: This 40-year postoperative follow-up of patients with childhood ET who underwent strabismus surgery by a single surgeon in Sweden showed that multiple surgeries and presence of postoperative adduction deficit were the most important factors influencing the incidence of consecutive XT after surgery. Presence of uncorrected amblyopia did not alter the prognosis for long-term development of consecutive XT.

  • 35.
    Germundsson, Johan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion.
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Phototherapeutic keratectomy in Salzmann's nodular degeneration2004In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 82, no 2, 148-153 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: To describe the outcome in vision and refraction of phototherapeutic keratectomy (PTK) in Salzmann's nodular degeneration (SND). Methods: Five eyes of four patients underwent PTK with the objective of restoring an acceptable refractive status and improving visual acuity. This surgical technique aims to make the nodules level with the corneal surface using an excimer laser. Results: Best corrected visual acuity (BCVA) improved in all five eyes. Astigmatism was reduced in four eyes and increased somewhat in one. During the observation period one eye suffered a late recurrence that required a penetrating graft. Conclusion: Salzmann's nodular degeneration is a rare disease that is sometimes difficult to diagnose as it has some resemblance to other diseases. The aetiology of the disease is unknown. Phototherapeutic keratectomy is a safe and effective mode of treatment. Recurrences occur with time. Copyright © Acta Ophthalmol Scand 2004.

  • 36.
    Germundsson, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Koulikovska, Marina
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    An Accurate Method to Determine Bowmans Layer Thickness In Vivo in the Human Cornea2012In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 53, no 4, 2354-2359 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To determine an accurate value for Bowmans layer (BL) thickness in vivo in humans. less thanbrgreater than less thanbrgreater thanMETHODS. Seventeen corneal transplant patients were examined preoperatively by laser-scanning in vivo confocal microscopy (IVCM), and corneal buttons were removed post-operatively and sectioned for light microscopy (LM). Nine corneas with uniformly thick BL by LM were used for thickness measurement. In the uniformly thick samples, probable overestimation of BL thickness in vivo by a first in vivo method (Method 1) led to the development of a revised in vivo method (Method 2). Method 2 was used to measure BL thickness in 20 healthy volunteers. less thanbrgreater than less thanbrgreater thanRESULTS. In nine patients, mean BL thickness prior to transplantation was 13.7 +/- 1.6 mu m by IVCM (Method 1) while BL thickness of the removed corneal button was 9.7 +/- 1.7 mu m by LM (P andlt; 0.001). The correlation of BL thickness between IVCM (Method 1) and LM was poor (P = 0.226). In 20 right eyes of 20 normal corneas, both in vivo methods were used to determine BL thickness. Mean BL thickness by Method 1 was 13.2 +/- 1.6 mu m and by Method 2 was 9.1 +/- 1.4 mu m (P andlt; 0.001). BL thickness measurements by both in vivo methods were highly correlated (P andlt; 0.001). less thanbrgreater than less thanbrgreater thanCONCLUSION. BL thickness by a revised in vivo method was close to LM values in this study and to values reported in fixed tissue in other studies. The authors believe this revised method provides the most accurate estimates of BL thickness in vivo to date.

  • 37.
    Germundsson, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Clinical Outcome and Recurrence of Epithelial Basement Membrane Dystrophy after Phototherapeutic Keratectomy A Cross-sectional Study2011In: OPHTHALMOLOGY, ISSN 0161-6420, Vol. 118, no 3, 515-522 p.Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate the outcome of phototherapeutic keratectomy (PTK) treatment of epithelial basement membrane dystrophy (EBMD) patients and to examine clinical and morphologic signs of recurrent dystrophy. Design: Cross-sectional, clinic-based study. Participants: Fifty-two eyes of 39 patients diagnosed with EBMD who underwent PTK between 2001 and 2008. Methods: Preoperative symptoms, best spectacle-corrected visual acuity (BSCVA), and refraction data were collected. At follow-up, refraction and BSCVA were measured, symptoms were noted, and slit-lamp biomicroscopy and in vivo confocal microscopy (IVCM) were performed. Main Outcome Measures: Best spectacle-corrected visual acuity and signs of recurrent EBMD based on symptoms and morphologic features. An assessment of EBMD severity after PTK additionally was considered. Results: Mean follow-up time was 43 months (range, 7-100 months). After PTK, BSCVA remained unchanged or improved in 49 (98%) of 51 eyes. Twenty-four (46%) of 52 eyes had recurrence of some form, and recurrence was correlated positively with postoperative time (P andlt; 0.001). Symptomatic recurrence occurred in 7 eyes (13%), whereas morphologic recurrence occurred in 21 eyes (40%). Symptoms were coupled with positive IVCM findings in 3 (43%) of 7 cases and with slit-lamp findings in 1 (14%) of 7 cases. Of 17 eyes with morphologic recurrence by IVCM, 9 eyes (53%) were classified as having grade 1 recurrence, 8 eyes (47%) were classified as having grade 2 recurrence, and none were classified as having grade 3 recurrence. Morphologic recurrence was associated with epithelial removal by laser ablation before PTK. Conclusions: Although PTK is an effective method of alleviating the clinical symptoms of EBMD, the dystrophy can recur with time. The relationship between the postoperative development of clinical symptoms and the corneal morphologic features is complex and requires further investigation.

  • 38.
    Germundsson, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH. Linköping University, Faculty of Health Sciences.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Letter: Corneal Dystrophy Recurrence Reply2011In: BMC Ophthalmology, ISSN 1471-2415, E-ISSN 1471-2415, Vol. 118, no 6, 1223-1224 p.Article in journal (Other academic)
  • 39.
    Germundsson, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Karanis, Georgios
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Age-Related Thinning of Bowman's Layer in the Human Cornea In Vivo2013In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 54, no 9, 6143-6149 p.Article in journal (Refereed)
    Abstract [en]

    Purpose. To determine the thickness of Bowman's layer (BL) in vivo in a healthy population and to determine its variation with age.

    Methods. Eighty-two subjects aged 15 to 88 years with clear, healthy corneas were examined bilaterally with laser scanning in vivo confocal microscopy (IVCM). Bowman's layer thickness was determined from IVCM images of anterior and posterior BL boundaries. For a given eye, BL thickness was averaged across four central locations by two independent observers. In addition, central corneal thickness was measured by time-domain optical coherence tomography.

    Results. A significant negative correlation of BL thickness with age was found in right eyes (Pearson r = −0.579, P < 0.0001) and in left eyes (r = −0.558, P < 0.0001). Linear regression analysis yielded a decline in BL thickness of 0.06 μm per year. In 41 older subjects (mean age, 64.4 years), BL thickness was significantly thinner (mean ± SD, 8.6 ± 1.7 μm in right eyes) than that in 41 younger subjects (mean age, 31.6 years) (mean ± SD, 10.7 ± 1.6 μm in right eyes) (P < 0.001). No correlation of corneal thickness with age or of BL thickness with corneal thickness was observed. Strong intereye correlations in BL thickness (r = 0.771, P < 0.0001) and corneal thickness (r = 0.969, P < 0.001) were found.

    Conclusions. Bowman's layer thins with age in the normal cornea, losing one-third of its thickness between the ages of 20 and 80 years. In vivo measurement of BL thickness by IVCM could aid in clinical assessment and planned treatments of the anterior cornea.

  • 40.
    Griffith, May
    et al.
    University of Ottawa.
    Jackson, W B
    University of Ottawa.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Merrett, K
    University of Ottawa.
    Li, F
    University of Ottawa.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Artificial corneas: a regenerative medicine approach2009In: EYE, ISSN 0950-222X, Vol. 23, no 10, 1985-1989 p.Article in journal (Refereed)
    Abstract [en]

    Corneal substitutes are being developed to address the shortage of human donor tissues as well as the current disadvantages in some clinical indications, which include immune rejection. In the past few years, there have been significant developments in bioengineered corneas that are designed to replace part or the full thickness of damaged or diseased corneas that range from keratoprostheses that solely address the replacement of the corneas function, through tissue-engineered hydrogels that permit regeneration of host tissues. We describe examples of corneal substitutes that encourage regeneration of the host tissue. We also contend that it is unlikely that there will be a single "one-size-fits-all corneal substitute for all indications. Instead, there will most likely be a small range of corneal substitutes ranging from prostheses to tissue-engineered matrix substitutes that are tailored to different clusters of clinical indications. The tissue-engineered matrices can either be produced as sterile acellular matrices, or complete with functional cells, ready for implantation.

  • 41.
    Hackett, Joanne M.
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Merrett, Kimberley
    University of Ottawa Eye Institute.
    Edelhauser, Henry
    Emory University School of Medicine.
    Sun, Yifei
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Gan, Lisha
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Biosynthetic corneal implants for replacement of pathologic corneal tissue: performance in a controlled rabbit alkali burn model2011In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 52, no 2, 651-657 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate the performance of structurally reinforced, stabilized recombinant human collagen-phosphorylcholine (RHCIII-MPC) hydrogels as corneal substitutes in a rabbit model of severe corneal damage.

    Methods: One eye each of 12 rabbits received a deep corneal alkali wound. Four corneas were implanted with RHCIII-MPC hydrogels. The other eight control corneas were implanted with either allografts or a simple crosslinked RHCIII hydrogel. In all cases, 6.25 mm diameter, 350 µm thick buttons were implanted by anterior lamellar keratoplasty to replace damaged corneal tissue. Implants were followed for nine months by clinical examination and in vivo confocal microscopy, after which implanted corneas were removed and processed for histopathological and ultrastructural examination.

    Results: Alkali exposure induced extensive central corneal scarring, ocular surface irregularity, and neovascularization in one case. All implants showed complete epithelial coverage by four weeks post-operative, but with accompanying suture-induced vascularization in 6/12 cases. A stable, stratified epithelium with hemidesmosomal adhesion complexes regenerated over all implants, and subbasal nerve regeneration was observed in allograft and RHCIII-MPC implants. Initially acellular biosynthetic implants were populated with host-derived keratocytes as stromal haze subsided and stromal collagen was remodeled. Notably, RHCIII-MPC implants exhibited resistance to vascular ingrowth while supporting endogenous cell and nerve repopulation.

    Conclusion: Biosynthetic implants based on RHC promoted cell and nerve repopulation in alkali burned rabbit eyes. In RHCIII-MPC implants, evidence of an enhanced resistance to neovascularization was additionally noted.

  • 42.
    Hammar, Björn
    et al.
    Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH. Linköping University, Faculty of Health Sciences.
    Björck, Erik
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
    Lind, Helena
    Hudiksvall Hospital, Hudiksvall, Sweden.
    Lagerstedt, Kristina
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
    Dellby, Anette
    Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Dystrophia Helsinglandica: a new type of hereditary corneal recurrent erosions with late subepithelial fibrosis2009In: Acta ophthalmologica, ISSN 1755-3768, Vol. 87, no 6, 659-667 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: To describe the phenotype of an autosomal-dominant corneal dystrophy with an early onset of recurrent corneal erosions and development of subepithelial fibrosis in the cornea, and also to exclude genetic linkage to known corneal dystrophies with autosomal-dominant inheritance and clinical resemblance.

    Methods: We describe the medical history and clinical findings in individuals from a seven-generation family with recurrent corneal erosions. A total of 43 individuals were evaluated by ophthalmological examination. Genomic DNA was prepared from peripheral blood and polymorphic microsatellite markers were analysed to study haplotypes surrounding genes causing corneal dystrophies with similar phenotypes.

    Results: Erosive symptoms usually lasted for between 1 and 10 days. By the age of 7 almost all of the affected individuals suffered from recurrent corneal erosions. The attacks generally declined in frequency and intensity from the late 20s, but all examined individuals had developed subepithelial fibrosis by the age of 37. The fibrosis generally started in the mid periphery and was followed in some family members by central fibrosis and the development of gelatinous superficial elevations. Only a marginal reduction of visual acuity was seen in a few individuals. The affected individuals did not share haplotypes for genetic microsatellite markers surrounding genes that are known to cause autosomal-dominant corneal dystrophies.

    Conclusion: We describe a new type of autosomal-dominant corneal disorder with recurrent corneal erosions and subepithelial fibrosis not significantly affecting visual acuity.

  • 43.
    Hammar, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Björk, Erik
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Lagerstedt, Kristina
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Dellby, Anette
    Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    A new corneal disease with recurrent erosive episodes and autosomal-dominant inheritance2008In: Acta Ophthalmologica, ISSN 1755-375X, Vol. 86, no 7, 758-763 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: The aim of this study was to characterize the phenotype in a large family with autosomal-dominant recurrent corneal erosions, and also to exclude genetic linkage to known autosomal-dominant inherited corneal dystrophies with clinical resemblance.

    Methods: We describe the medical history and clinical findings in patients from a six-generation family with recurrent corneal erosions. A total of 28 individuals were evaluated by ophthalmological examination. Genomic DNA was prepared from peripheral blood and analysed with polymorphic microsatellite markers close to known genes causing autosomal-dominant corneal dystrophies.

    Results: The patients had erosive symptoms that usually lasted from 1 to 7 days. The symptoms were described as early as at 8 months of age, and by the age of 5 the majority of the affected individuals suffered from recurrent corneal erosions. The attacks generally declined in frequency and intensity with age, and 52% of the patients developed central keloid-like corneal opacities. Nine patients received corneal grafts, and recurrences were seen in all grafts. The affected patients did not share haplotypes for genetic microsatellite markers surrounding known genes causing autosomal-dominant corneal dystrophies.

    Conclusion: We describe a new hereditary disease with recurrent corneal erosions. Attacks of symptoms similar to recurrent erosions dominate the phenotype, but half of those affected also developed corneal, keloid-like, central opacities. This disorder was not genetically linked to any clinically resembling corneal dystrophies with autosomal-dominant inheritance.

  • 44.
    Hammar, Björn
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology.
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL.
    Autosomal dominant recurrent erosions - from non-existing to being everywhere2007In: European Association for Vision and Eye Research,2007, 2007, 2426-2426 p.Conference paper (Other academic)
  • 45.
    Hammar, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Lagali, Neil
    Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences.
    Ek, Stefan
    Department of Ophthalmology, Sahlgrenska University Hospital, Mölndal, Sweden.
    Seregard, Stefan
    St Eriks Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
    Dellby, Anette
    Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Dystrophia Smolandiensis - recurrent corneal erosions with a novel morphological picture2010In: Acta Ophthalmologica, ISSN 1755-375X, Vol. 88, no 4, 394-400 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: The aim of this study was to describe morphological changes in a new corneal disease, Dystrophia Smolandiensis, characterized by recurrent corneal erosive episodes and formation of central corneal keloid-like opacities in approximately half of those affected.

    Methods: The corneas of seven affected individuals were examined using in-vivo confocal microscopy. Specimens of one primary corneal graft, one regraft, and one biopsied keloid-like region, obtained from members of a large family with the disease, were re-examined with a light microscope, and sections were stained with Congo red and immunohistochemically analyzed for fibronectin and S100A4.

    Results: Light microscopic examination revealed epithelial hyperplasia, absence of Bowman’s layer and subepithelial fibrosis. Fibronectin was expressed in the area of subepithelial fibrosis, and the keratocytes in this area generally expressed S100A4. The biopsy specimen stained positive for Congo red, suggesting an amyloid deposit. In-vivo confocal microscopy confirmed epithelial abnormalities, loss of Bowman’s layer, and significant alterations of the subbasal nerve plexus in affected individuals.

    Conclusion: The morphologic picture in Dystrophia Smolandiensis is novel for a condition dominated by recurrent corneal erosions at the clinical level. Although no single morphologic feature unique to the disease could be found, the general morphologic pattern of pathology (true keloid formation, an absence of Bowman’s layer, subepithelial fibrosis, and abnormal subbasal nerves) likely reflects a novel phenotypic expression of the healing response to recurrent erosion of the corneal epithelium. The pathogenesis of Dystrophia Smolandiensis, however, remains to be fully elucidated.

  • 46.
    Ihnatko, Robert
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Edén, Ulla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Congenital Aniridia and the Ocular Surface2016In: OCULAR SURFACE, ISSN 1542-0124, Vol. 14, no 2, 196-206 p.Article in journal (Refereed)
    Abstract [en]

    Aniridia is a congenital pan-ocular disorder caused by haplo-insufficiency of Pax6, a crucial gene for proper development of the eye. Aniridia affects a range of eye structures, including the cornea, iris, anterior chamber angle, lens, and fovea. The ocular surface, in particular, can be severely affected by a progressive pathology termed aniridia-associated keratopathy (AAK), markedly contributing to impaired vision. The purpose of this review is to provide an update of the current knowledge of the genetic, clinical, micro-morphological, and molecular aspects of AAK. We draw upon material presented in the literature and from our own observations in large aniridia cohorts. We summarize signs and symptoms of AAK, describe current options for management, and discuss the latest research findings that may lead to better diagnosis and new treatment or prevention strategies for this debilitating ocular surface condition.

  • 47.
    Ihnatko, Robert
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Edén, Ulla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Dellby, Anette
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Analysis of protein composition and protein expression in the tear fluid of patients with congenital aniridia2013In: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 94, 78-88 p.Article in journal (Refereed)
    Abstract [en]

    Aniridia is a rare congenital genetic disorder caused by haploinsuffiency of the PAX6 gene, the master gene for development of the eye. The expression of tear proteins in aniridia is unknown. To screen for proteins involved in the aniridia pathophysiology, the tear fluid of patients with diagnosed congenital aniridia was examined using two-dimensional electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two-dimensional map of tear proteins in aniridia has been established and 7 proteins were differentially expressed with P less than 0.01 between aniridia patients and control subjects. Five of them were more abundant in healthy subjects, particularly alpha-enolase, peroxiredoxin 6, cystatin S, gelsolin, apolipoprotein A-1 and two other proteins, zinc-alpha 2-glycoprotein and lactoferrin were more expressed in the tears of aniridia patients. Moreover, immunoblot analysis revealed elevated levels of vascular endothelial growth factor (VEGF) in aniridia tears which is in concordance with clinical finding of pathological blood and lymph vessels in the central and peripheral cornea of aniridia patients. The proteins with different expression in patients tears may be new candidate molecules involved in the pathophysiology of aniridia and thus may be helpful for development of novel treatment strategies for the symptomatic therapy of this vision threatening condition. Biological significance This study is first to demonstrate protein composition and protein expression in aniridic tears and identifies proteins with different abundance in tear fluid from patients with congenital aniridia vs. healthy tears.

  • 48.
    Islam, Mohammad Mirazul
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Ravichandran, Ranjithkumar
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Olsen, D.
    FibroGen Inc, CA 94158 USA.
    Kozak Ljunggren, Monika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Lee, Chyan-Jang
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics. Linköping University, The Institute of Technology. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Phopase, Jaywant
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Self-assembled collagen-like-peptide implants as alternatives to human donor corneal transplantation2016In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 6, no 61, 55745-55749 p.Article in journal (Refereed)
    Abstract [en]

    Extracellular matrix proteins like collagen promote regeneration as implants in clinical studies. However, collagens are large and unwieldy proteins, making small functional peptide analogs potentially ideal substitutes. Self-assembling collagen-like-peptides conjugated with PEG-maleimide were assembled into hydrogels. When tested pre-clinically as corneal implants in mini-pigs, they promoted cell and nerve regeneration, forming neo-corneas structurally and functionally similar to natural corneas.

  • 49.
    Koh, Li Buay
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics. Linköping University, The Institute of Technology.
    Islam, Mohammad Mirazul
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Swedish Nanoscience Center, Karolinska Institute, Stockholm , Sweden .
    Mitra, Debbie
    Ottawa Hospital Research Institute, University of Ottawa Eye Institute, ON, Canada.
    Noel, Christopher
    Ottawa Hospital Research Institute, University of Ottawa Eye Institute, ON, Canada.
    Merett, Kimberley
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Ottawa Hospital Research Institute, University of Ottawa Eye Institute, ON, Canada.
    Odorcic, Silvia
    Ottawa Hospital Research Institute, University of Ottawa Eye Institute, ON, Canada.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Jackson, William Bruce
    Ottawa Hospital Research Institute, University of Ottawa Eye Institute, ON, Canada.
    Liedberg, Bo
    Center for Biomimetic Sensor Science, Nanyang Technological University, Singapore.
    Phopase, Jaywant
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics. Linköping University, The Institute of Technology.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Swedish Nanoscience Center, Karolinska Institute, Stockholm, Sweden.
    Epoxy Cross-Linked Collagen and Collagen-Laminin Peptide Hydrogels as Corneal Substitutes2013In: Journal of Functional Biomaterials, ISSN 2079-4983, E-ISSN 2079-4983, Vol. 4, no 3, 162-177 p.Article in journal (Refereed)
    Abstract [en]

    A bi-functional epoxy-based cross-linker, 1,4-Butanediol diglycidyl ether (BDDGE), was investigated in the fabrication of collagen based corneal substitutes. Two synthetic strategies were explored in the preparation of the cross-linked collagen scaffolds. The lysine residues of Type 1 porcine collagen were directly cross-linked using l,4-Butanediol diglycidyl ether (BDDGE) under basic conditions at pH 11. Alternatively, under conventional methodology, using both BDDGE and 1-Ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) as cross-linkers, hydrogels were fabricated under acidic conditions. In this latter strategy, Cu(BF4)2·XH2O was used to catalyze the formation of secondary amine bonds. To date, we have demonstrated that both methods of chemical cross-linking improved the elasticity and tensile strength of the collagen implants. Differential scanning calorimetry and biocompatibility studies indicate comparable, and in some cases, enhanced properties compared to that of the EDC/NHS controls. In vitro studies showed that human corneal epithelial cells and neuronal progenitor cell lines proliferated on these hydrogels. In addition, improvement of cell proliferation on the surfaces of the materials was observed when neurite promoting laminin epitope, IKVAV, and adhesion peptide, YIGSR, were incorporated. However, the elasticity decreased with peptide incorporation and will require further optimization. Nevertheless, we have shown that epoxy cross-linkers should be further explored in the fabrication of collagen-based hydrogels, as alternatives to or in conjunction with carbodiimide cross-linkers.

  • 50.
    Koulikovska, Marina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Podskochy, Alexander
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Expression of the chaperonin containing T-complex polypeptide 1 chaperonin subunit during corneal wound healing2003In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 44, 854- p.Conference paper (Other academic)
12 1 - 50 of 93
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