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  • 1.
    Austeng, Dordi
    et al.
    Uppsala University, Sweden University of Trondheim Hospital, Norway .
    Kallen, Karin
    Lund University, Sweden .
    Hellstrom, Ann
    University of Gothenburg, Sweden .
    Jakobsson, Peter
    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.
    Lundgren, Pia
    Umeå University, Sweden .
    Tornqvist, Kristina
    University of Lund Hospital, Sweden .
    Wallin, Agneta
    St Eriks Eye Hospital, Sweden .
    Holmstrom, Gerd
    Uppsala University, Sweden .
    Regional differences in screening for retinopathy of prematurity in infants born before 27 weeks of gestation in Sweden - the EXPRESS study2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 4, p. 311-315Article in journal (Refereed)
    Abstract [en]

    Purpose: The primary aim was to analyse regional incidences of retinopathy of prematurity (ROP) and frequencies of treatment and their relation to perinatal risk factors during a 3-year period. A secondary aim was to study adherence to the study screening protocol in the different regions. Methods: A population-based study of neonatal morbidity in extremely preterm infants in Sweden (EXPRESS) was performed during 2004-2007. Screening for ROP was to start at postnatal age 5weeks and to continue weekly until the retina was completely vascularized or until regression of ROP. Logistic regression analyses were used for evaluation of differences in incidence of Any ROP, ROP 3 or more and ROP Type 1 between the seven regions of the country. Results: The regional incidence of ROP varied between 54% and 92% for Any ROP, between 25% and 43% for ROP stage 3 or more and between 8% and 23% of infants with ROP Type 1, all of whom were treated. There was no significant difference between the regions regarding ROP Type 1, even when adjusting for known risk factors for ROP. Conclusion: The heterogeneity between the regions regarding the incidence of ROP was reduced with increasing severity of ROP, and there was no heterogeneity regarding frequency of treatment for ROP, which is the most important issue for the children. We cannot exclude observer bias regarding mild ROP and ROP stage 3 in this study.

  • 2.
    Bourghardt Peebo, Beatrice
    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.
    Angiogenesis from a new perspective2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Angiogenesis is the emergence of new blood and lymph vessels from existing ones. In the pathologic form it contributes to the onset and progression of numerous different human disorders such as cancer, inflammation, atherosclerosis and blinding eye diseases. There exist a number of models to study angiogenesis, both in vitro and in vivo, but there is no single perfect model so far. Consequently there is a need to develop new angiogenesis assays for evaluating blood and lymph vessel behaviour in different physiologic settings.

    The aim of this thesis was to gain insight into in vivo angiogenesis introducing a new technique in an inflammatory corneal model. The method involved in vivo examination of the cornea and subsequent comparison of in vivo findings with ex vivo immunohistochemical analysis of the same tissue samples. An existing suture model for inflammatory angiogenesis in the cornea was modified for in vivo observations with a clinically-approved corneal confocal microscope.

    In this thesis, corneal lymph vessels were characterized for the first time in vivo and findings from the experimental bench could be applied in a clinical setting, where presumed lymphatics were observed in a corneal transplant patient with rejection. Furthermore, the technique was extended to investigate time-lapse processes in sprouting and regressing capillaries, and led to a number of new observations. CD11b+ myeloid cells constitute the first bulk of infiltrating inflammatory cells and contribute to inflammatory sprouting and regression in numerous ways including pre-patterning of the corneal stroma and guiding of capillary sprouts. Newly formed hemangiogenic sprouts are perfused with a slow-moving fluid and have a lumen. In blood vessel regression, capillary remodeling occurred by abandonment of sprout tips in close association with macrophages and vascular loops formed by presumed intussusceptive angiogenesis. In addition, a network of pericyte- and endothelium-free basement membrane tubes was formed after desertion or degradation of vascular endothelium in former corneal capillaries.

    In conclusion, we introduce a new in vivo technique for investigating angiogenesis in a corneal model were in vivo findings can be interpreted with ex vivo definitions of specific cell types by immunohistochemistry. Findings from pre-clinical experiments have been possible to apply in a clinical setting when examining patients with corneal pathology.

    List of papers
    1. Cellular-Level Characterization of Lymph Vessels in Live, Unlabeled Corneas by In Vivo Confocal Microscopy
    Open this publication in new window or tab >>Cellular-Level Characterization of Lymph Vessels in Live, Unlabeled Corneas by In Vivo Confocal Microscopy
    2010 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 51, no 2, p. 830-835Article in journal (Refereed) Published
    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.

    Place, publisher, year, edition, pages
    Rockville, MD, United States: , 2010
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-53820 (URN)10.1167/iovs.09-4407 (DOI)000273704700030 ()
    Available from: 2010-02-05 Created: 2010-02-05 Last updated: 2018-01-22Bibliographically approved
    2. Letter: In vivo confocal microscopy visualization of presumed lymph vessels in a case of corneal transplant rejection
    Open this publication in new window or tab >>Letter: In vivo confocal microscopy visualization of presumed lymph vessels in a case of corneal transplant rejection
    2011 (English)In: Clinical and Experimental Ophthalmology, ISSN 1442-6404, E-ISSN 1442-9071, Vol. 39, no 8, p. 832-834Article in journal, Letter (Other academic) Published
    Abstract [en]

    n/a

    Place, publisher, year, edition, pages
    Wiley-Blackwell, 2011
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-72259 (URN)10.1111/j.1442-9071.2011.02557.x (DOI)000296913900016 ()
    Available from: 2011-11-24 Created: 2011-11-24 Last updated: 2018-01-22Bibliographically approved
    3. Time-Lapse In Vivo Imaging of Corneal Angiogenesis: The Role of Inflammatory Cells in Capillary Sprouting
    Open this publication in new window or tab >>Time-Lapse In Vivo Imaging of Corneal Angiogenesis: The Role of Inflammatory Cells in Capillary Sprouting
    2011 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 52, no 6, p. 3060-3068Article in journal (Refereed) Published
    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.

    Place, publisher, year, edition, pages
    Research in Vision and Opthalmology, 2011
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-69178 (URN)10.1167/iovs.10-6101 (DOI)000291100800026 ()
    Note
    Original Publication: Beatrice Bourghardt Peebo, Per Fagerholm, Catharina Traneus-Rockert and Neil Lagali, Time-Lapse In Vivo Imaging of Corneal Angiogenesis: The Role of Inflammatory Cells in Capillary Sprouting, 2011, INVESTIGATIVE OPHTHALMOLOGY and VISUAL SCIENCE, (52), 6, 3060-3068. http://dx.doi.org/10.1167/iovs.10-6101 Copyright: Research in Vision and Opthalmology http://www.arvo.org/Available from: 2011-06-17 Created: 2011-06-17 Last updated: 2018-01-22Bibliographically approved
    4. Cellular level characterization of capillary regression in inflammatory angiogenesis using an in vivo corneal model
    Open this publication in new window or tab >>Cellular level characterization of capillary regression in inflammatory angiogenesis using an in vivo corneal model
    2011 (English)In: Angiogenesis, ISSN 0969-6970, E-ISSN 1573-7209, Vol. 14, no 3, p. 393-405Article in journal (Refereed) Published
    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.

    Place, publisher, year, edition, pages
    Springer Verlag (Germany), 2011
    Keywords
    Inflammation, Capillary regression, In vivo confocal microscopy, Cornea
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-70325 (URN)10.1007/s10456-011-9223-3 (DOI)000293922300015 ()
    Note
    The original publication is available at www.springerlink.com: Beatrice Bourghardt Peebo, Per Fagerholm, Catharina Traneus-Rockert and Neil Lagali, Cellular level characterization of capillary regression in inflammatory angiogenesis using an in vivo corneal model, 2011, Angiogenesis, (14), 3, 393-405. http://dx.doi.org/10.1007/s10456-011-9223-3 Copyright: Springer Verlag (Germany) http://www.springerlink.com/Available from: 2011-09-02 Created: 2011-09-02 Last updated: 2018-01-22
  • 3.
    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, p. 93-100Article 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.

  • 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.
    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, p. 832-834Article in journal (Other academic)
    Abstract [en]

    n/a

  • 5.
    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, p. 393-405Article 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.

  • 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, p. 3060-3068Article 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.
    Czajka, Marcin Piotr
    et al.
    Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Frajdenberg, Agata
    Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Johansson, Björn
    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. St. Erik Eye Hospital, Stockholm, Sweden.
    Outcomes after combined 1.8-MM microincision cataract surgery and 23-gauge transconjunctival vitrectomy for posterior segment disease: a retrospective study2014In: Retina, ISSN 0275-004X, E-ISSN 1539-2864, Vol. 34, no 1, p. 142-148Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    The aim of the study was to retrospectively review indications, intraoperative and postoperative complications, and outcomes of combined coaxial microincision cataract surgery and 23-gauge vitrectomy for posterior segment disease.

    METHODS:

    The outcomes and findings of surgery in 50 patients (50 eyes) who underwent coaxial microincision cataract surgery and foldable intraocular lens implantation combined with 23-gauge vitrectomy for a variety of indications between January 2010 and March 2012.

    RESULTS:

    No posterior capsule tear was observed during surgery. Intraoperatively, a retinal break was found in 9 eyes (18%), which were successfully treated with laser and/or cryotherapy. Corneal suture was done in 6 eyes (12%), 5 of them left and 1 right. Sclerotomy was sutured in 2 left and 2 right eyes, respectively, a total of 4 eyes (8%). In 1 case, 23-gauge vitrectomy was converted to 20-gauge vitrectomy. The postoperative intraocular pressure (millimeters of mercury, mean ± standard deviation) was 16.7 ± 9.8. Hypotony (intraocular pressure < 9 mmHg) occurred in 9 eyes (18%). In 1 eye (2%) posterior iris synechia were observed 2 weeks after surgery, and intraocular pressure was >40 mmHg. Intraocular pressure was normalized after Nd:YAG laser iridotomy. Fibrin reaction in the anterior chamber was observed in 1 eye (2%) Day 1 after surgery. Posterior capsule opacification, which required Nd:YAG laser capsulotomy, was observed in 11 eyes (22%) during the follow-up.

    CONCLUSION:

    Combined sutureless coaxial microincision cataract surgery and 23-gauge vitrectomy offers the advantages of both coaxial microincision cataract surgery (less wound leakage, good anterior chamber stability, and safety) and 23-gauge vitrectomy (decreased inflammation and faster rehabilitation after surgery).

  • 8.
    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, p. 1803-1810Article 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.

  • 9.
    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, p. E165-E167Article in journal (Other academic)
    Abstract [en]

    n/a

  • 10.
    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, p. 347-347Article in journal (Other academic)
    Abstract [en]

    n/a

  • 11.
    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, p. 2420-2427Article 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.

  • 12.
    Frennesson, Christina
    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.
    Nilsson, Sven Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    A three-year follow-up of ranibizumab treatment of exudative AMD: impact on the outcome of carrying forward the last acuity observation in drop-outs2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 3, p. 216-220Article in journal (Refereed)
    Abstract [en]

    Abstract. Purpose: To analyse a 3-year clinical patient cohort of ranibizumab treatment of exudative age-related macular degeneration (AMD), to investigate the impact on visual outcome of carrying forward the last acuity observation in drop-outs and to explore possible differences between the early and the late phase of the study. Methods: A retrospective study of 312 eyes with neovascular AMD. The patients were followed up monthly, received three initial monthly injections of 0.5 mg ranibizumab and were re-treated pro re nata (PRN). Time-domain optical coherence tomography (TD-OCT) was used until spectral-domain (SD)-OCT was introduced during the last year of enrolment. Sixty-five patients were discontinued from the study. Primary outcome: change in best corrected visual acuity (BCVA). Results: Best corrected visual acuity was 58.4 (CI 56.9-59.9) ETDRS (Early Treatment Diabetic Retinopathy Study) letters. At three months, it had increased by 4.1 letters (p = 0.0004), at 12 months by 1.8 letters, at 24 months by 1.0 letter and at 36 months by 0.1 letter. However, if the last available acuity of drop-outs was carried forward one step and included, acuity had increased by 3.9 letters at 3 months (p less than 0.0001) and by 1.0 letter at 12 months but had decreased by 3.8 letters at 24 months (p = 0.019) and by 4.1 letters (p = 0.003) at 36 months. At 24 months, the result was significantly (p = 0.030) less favourable when drop-outs were included. In patients enrolled during the late phase, BCVA was 59.3 (CI 56.7-62.0). It had increased by 5.7 letters (p less than 0.0001) at three months and by 5.8 letters at 12 months (p = 0.0016). In patients enrolled during the early phase, BCVA was 57.9 (CI 55.0-60.8). At three months, it had increased by 3.5 letters (p = 0.0008), but at 12 months, it had decreased by 2.3 letters (ns). The result at 12 months was significantly (p = 0.0033) better for the late than for the early phase. The number of injections was also significantly (p = 0.011) higher in the late phase. Adverse events were similar to those in earlier clinical trials. Conclusions: The results of this 3-year cohort showed that the initial average acuity could be maintained over 36 months, which was comparable to those of many other clinical cohorts. However, if the last available acuity of drop-outs was carried forward one step and included, the acuity figures would have fallen significantly. The results in patients enrolled during the late phase of the study were fairly similar to those in clinical trials.

  • 13.
    Frennesson, Christina
    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.
    Wadelius, Claes
    Uppsala University, Sweden .
    Nilsson, Sven Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Best vitelliform macular dystrophy in a Swedish family: genetic analysis and a seven-year follow-up of photodynamic treatment of a young boy with choroidal neovascularization2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 3, p. 238-242Article in journal (Refereed)
    Abstract [en]

    Abstract. Purpose: To determine the mutation in a Swedish family with Best disease (vitelliform macular dystrophy; VMD) and to investigate the short- and long-term effects of photodynamic treatment (PDT) on subretinal neovascularization in a young boy. Methods: The five members of three generations of a family with VMD underwent a thorough ophthalmological examination, including best-corrected visual acuity (VA), visual field, colour vision, biomicroscopy of the posterior segment (dilated), fundus photography and electro-oculography (EOG). For the proband, an eleven-year-old boy, his father and grandfather, dark adaptation test, angiography and electroretinography (ERG) were also performed. After PCR amplification, the genotype was determined by cleavage with restriction enzyme, specific for the W93C allele. Results: Four family members had an abnormal EOG response. All showed the W93C mutation in the VMD2 gene. Visual acuity ranged from 20/20 to 20/250. The fundus manifestations varied from minor pigmentary changes over egg yolk-like lesions to chorioretinal atrophy, and fluorescein angiography showed corresponding pathology. In the proband, VA decreased during follow-up from 0.5 (20/40) to 0.08 (20/250) due to a subfoveal neovascularization with haemorrhage, and PDT with visudyne was begun. The haemorrhage resolved within 2 months, and after three treatments, VA had increased to 0.25 (20/80). One year later, acuity had improved to 0.5 (20/40), and this result was stable throughout the 7 years of the follow-up. Conclusion: The mutation was determined to be W93C, the most common mutation in VMD in Sweden. In an eleven-year-old boy with subretinal neovascularization, PDT seemed to be beneficial also in a long-term follow-up.

  • 14.
    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, p. 691-695Article 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.

  • 15.
    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, p. 2354-2359Article 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.

  • 16.
    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, p. 1223-1224Article in journal (Other academic)
  • 17.
    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, p. 6143-6149Article 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.

  • 18.
    Germundsson, Johan
    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.
    Pathologically reduced subbasal nerve density in epithelial basement membrane dystrophy is unaltered by phototherapeutic keratectomy treatment2014In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 55, no 3, p. 1835-1841Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate the effect of phototherapeutic keratectomy (PTK) treatment on corneal epithelial wing cell and corneal subbasal nerve density in epithelial basement membrane dystrophy (EBMD).

    METHODS: A total of 39 patients with EBMD who underwent PTK treatment, 40 healthy volunteers, and 24 untreated eyes with EBMD were examined with laser-scanning in vivo confocal microscopy (IVCM). Corneal subbasal nerves and epithelial wing cells were manually quantified from IVCM images by two observers, while epithelial wing cells were additionally quantified by a fully automated method.

    RESULTS: Subbasal nerve density was significantly reduced in untreated (10,164 ± 4139 μm/mm(2); n = 24) and PTK-treated (10,624 ± 4479 μm/mm(2); n = 39) EBMD eyes, relative to healthy controls (18,241 ± 4479 μm/mm(2); n = 40) (P < 0.001). Subbasal nerve density in PTK-treated and untreated eyes did not differ (P > 0.05). Epithelial wing cell density did not differ between PTK-treated and untreated EBMD eyes, by either manual or automated analysis; however, epithelial wing cell density in PTK-treated EBMD corneas was significantly reduced (P = 0.008) relative to healthy corneas, by automated cell counting.

    CONCLUSIONS: Subbasal nerve density in EBMD is reduced by 45% and recovers only to the reduced level in the long term after PTK treatment, whereas epithelial wing cell density in EBMD is not affected by PTK in the long term. Fully automated cell analysis from IVCM images could provide an objective, standardized means to quantify and compare corneal cell densities in future studies.

  • 19.
    Heintz, Emelie
    et al.
    Linköping University, Department of Medical and Health Sciences, Health Technology Assessment and Health Economics. Linköping University, Faculty of Health Sciences.
    Bourghardt Peebo, Beatrice
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Wiréhn, Ann-Britt
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Health Sciences.
    Rosenqvist, Ulf
    Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Department of Medical Specialist.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Health Technology Assessment and Health Economics. Linköping University, Faculty of Health Sciences.
    Health-related quality of life profiles of patients with diabetic retinopathyManuscript (preprint) (Other academic)
    Abstract [en]

    Purpose: There are various instruments for estimating health-related quality of life (HRQoL) in patients with diabetic retinopathy (DR). However, if the results are to be compared with those for other diseases, it is essential to use measures that are applicable to all disease areas. The aim of this study was to explore the HRQoL profiles of patients with DR using two generic multi-attribute instruments, the Health State Utilities Index Mark 3 (HUI-3) and the EQ-5D questionnaire, and to investigate these questionnaires’ sensitivity to differences in HRQoL due to DR.

    Methods: The study population comprised 166 Swedish diabetes patients diagnosed with DR at different severities. Patients were interviewed over the telephone using HUI-3 and EQ-5D. The vision-specific National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) was also included, to give an empirical framework for the results of the generic instruments. Linear and logistic regression models were used to adjust for possible confounders.

    Results: Patients with vision impairment (VI) reported lower scores in Vision, Ambulation, and Pain in HUI-3 and more problems with Usual activities and Anxiety/depression in EQ-5D. However, even though NEI VFQ-25 showed a negative association between DR severity and Mental health and Near activities, neither EQ-5D nor HUI-3 identified a negative relationship between DR severity and HRQoL.

    Conclusion: The generic instruments show lowered HRQoL for patients with VI in various dimensions but were not sensitive to decrements related to the diagnosis of DR alone. The questionnaire of HUI-3 was more sensitive than EQ-5D to differences in HRQoL due to DR-related VI.

  • 20.
    Heintz, Emelie
    et al.
    Linköping University, Department of Medical and Health Sciences, Health Technology Assessment and Health Economics. Linköping University, Faculty of Health Sciences.
    Wiréhn, Ann-Britt
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Health Sciences.
    Bourghardt Peebo, Beatrice
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Rosenqvist, Ulf
    Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Health Technology Assessment and Health Economics. Linköping University, Faculty of Health Sciences.
    QALY weights for diabetic retinopathy: a comparison of health state valuations with HUI-3, EQ-5D, EQ-VAS, and TTO.2012In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 15, no 3, p. 475-484Article in journal (Refereed)
    Abstract [en]

    Objective: To estimate quality-adjusted life-year weights for patients with diabetic retinopathy by using various methods and to investigate the empirical validity of the different measures.

    Methods: The study population comprised 152 patients with diabetes in Östergötland County, Sweden. Participants were interviewed by telephone by using the time trade-off (TTO) method and a visual analogue scale (EQ-VAS) (direct valuations) as well as the EuroQol five-dimensional questionnaire (EQ-5D) and the health utilities index mark 3 (HUI-3) (indirect valuations). The quality-adjusted life-year weights were adjusted for potential confounders by using analysis of covariance. The empirical validity of the measures was examined by testing their ability to detect hypothetical differences between severity levels of diabetic retinopathy and by investigating the correlation between the measures and the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25).

    Results: All measures detected significant differences in scores between patient groups classified according to visual impairment in the better eye (analysis of covariance, P < 0.05), but only HUI-3 and EQ-VAS detected significant differences between patient groups classified according to visual impairment or pathological progression in the worse eye. HUI-3 recorded a difference of 0.43 in values between normal vision and blindness in the better eye, which was more than twice the differences captured by the other measures (0.15–0.20). In addition, HUI-3 showed the highest correlation with NEI VFQ-25 (r = 0.54; P < 0.001).

    Conclusions: In cost-utility analyses, the choice of quality-adjusted life-year measure may affect whether an intervention is considered cost-effective. Furthermore, if decisions are to be based on values from the general public, HUI-3 can be recommended for cost-utility analyses of interventions directed at diabetic retinopathy.

  • 21.
    Holmstrom, Gerd E.
    et al.
    University of Uppsala Hospital, Sweden .
    Kallen, Karin
    Lund University, Sweden .
    Hellstrom, Ann
    University of Gothenburg, Sweden .
    Jakobsson, Peter
    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.
    Serenius, Fredrik
    Uppsala University, Sweden Umeå University, Sweden .
    Stjernqvist, Karin
    Lund University, Sweden .
    Tornqvist, Kristina
    University of Lund Hospital, Sweden .
    Ophthalmologic Outcome at 30 Months Corrected Age of a Prospective Swedish Cohort of Children Born Before 27 Weeks of Gestation The Extremely Preterm Infants in Sweden Study2014In: JAMA OPHTHALMOLOGY, ISSN 2168-6165, Vol. 132, no 2, p. 182-189Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Follow-up at 30 months corrected age reveals eye and visual problems in one-third of children born extremely prematurely (less than27 weeks gestation). OBJECTIVE To investigate the ophthalmologic outcome of extremely preterm children at 30 months corrected age. DESIGN, SETTING, AND PARTICIPANTS A prospective, population-based follow-up study (Extremely Preterm Infants in Sweden Study [EXPRESS]) was conducted in Sweden. The population included extremely preterm infants (less than27 weeks gestation) born in Sweden between 2004 and 2007, of whom 491 survived until age 2.5 years. Screening for retinopathy of prematurity (ROP) was performed in the neonatal period. At 30 months corrected age, an ophthalmologic assessment was performed in 411 of 491 children (83.7%). MAIN OUTCOMES AND MEASURES Visual acuity, manifest strabismus, and refractive errors were evaluated. RESULTS Visual impairment was identified in 3.1% of the children, and 1.0% were blind. Refractive errors, defined as myopia less than -3 diopters (D), hypermetropia greater than +3 D, astigmatism 2 D or more, and/or anisometropia 2 D or more, were found in 25.6% of the children, and 14.1% had manifest strabismus. There were significant associations between visual impairment and treated ROP (P = .02), cognitive disability (P less than .001), and birth weight (P = .02). Multiple regression analyses revealed significant associations between strabismus and treated ROP (P less than .001), cognitive disability (P less than .01), and cerebral palsy (P = .02). Refractive errors were significantly correlated with severity of ROP (right eye, P less than .001; left eye, P less than .01). Children who had been treated for ROP had the highest frequency (69.0%) of eye and visual abnormalities. CONCLUSIONS AND RELEVANCE One-third of the extremely prematurely born children in this study had some kind of eye or visual problems, such as visual impairment, strabismus, or major refractive error. Despite being born extremely preterm, the present cohort has a similar prevalence of blindness and visual impairment as in previous Swedish cohorts of children born less prematurely.

  • 22.
    Holmström, Gerd E.
    et al.
    Uppsala University Hospital, Sweden.
    Hellström, Ann
    University of Gothenburg, Sweden .
    Jakobsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Lundgren, Pia
    Umeå University, Sweden .
    Tornqvist, Kristina
    Lund University Hospital, Sweden .
    Wallin, Agneta
    St Eriks Eye Hospital, Stockholm, Sweden .
    Swedish National Register for Retinopathy of Prematurity (SWEDROP) and the Evaluation of Screening in Sweden2012In: Archives of ophthalmology (1960), ISSN 0003-9950, Vol. 130, no 11, p. 1418-1424Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate screening for retinopathy of prematurity (ROP) in Sweden and to investigate possible modifications of the present screening guidelines. less thanbrgreater than less thanbrgreater thanMethods: Infants in Sweden with a gestational age (GA) of 31 weeks + 6 days or less are screened for ROP. Data from the Swedish national register for ROP (SWEDROP) during 2008 and 2009 were extracted and compared with a national perinatal quality register. less thanbrgreater than less thanbrgreater thanResults: In SWEDROP, there were 1791 infants born before a GA of 32weeks from January 1, 2008, through December 31, 2009. Another 70 infants were registered in the perinatal quality register but not in SWEDROP (drop-out rate, 3.8% [70 of 1861 infants]). Seven infants died before termination of screening. In the final study cohort (1784 infants), 15.6% had mild ROP and 8.5% had severe ROP. Treatment was performed in 4.4% of the infants, none of whom had a GA at birth of more than 28 weeks. Nine infants with a GA of more than 28 weeks at birth developed stage 3 ROP, which regressed spontaneously. The total number of examinations was 9286 (964 in infants with a GA of 31 weeks), and the mean (range) number of examinations of each infant was 5.2 (1-30). less thanbrgreater than less thanbrgreater thanConclusions: The SWEDROP, a quality register for ROP, has a national coverage (ie, participation) of 96%. Data from 2008 to 2009 show that it seems possible to reduce the upper limit for screening in Sweden by 1 week, including only infants with a GA of 30 weeks + 6 days or less. However, such a change should be combined with a strong recommendation to neonatologists to refer also severely ill and more "mature" infants.

  • 23. Huang, Yumin
    et al.
    Al-Hawasi, Abbas
    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.
    Eveman, Inger
    Link, Hans
    Kvantifiering av retinal axon och neuron vid MS med OCT2014In: BestPractice: Multipel Skleros, Vol. 7, p. 22-25Article in journal (Other academic)
  • 24.
    Huang-Link, Yu-Min
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Al-Hawasi, Abbas
    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.
    Eveman, Inger
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Letter: Retrograde degeneration of visual pathway: Hemimacular thinning of retinal ganglion cell layer in progressive and active multiple sclerosis2014In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 261, no 12, p. 2453-2456Article in journal (Other academic)
    Abstract [en]

    n/a

  • 25.
    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, p. 78-88Article 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.

  • 26.
    Karlsson, Markus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Frennesson, Christina
    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.
    Gustafsson, Therese
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Brunk, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Erik Nilsson, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Kurz, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Autophagy of iron-binding proteins may contribute to the oxidative stress resistance of ARPE-19 cells2013In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 116, p. 359-365Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to elucidate possible reasons for the remarkable resistance of human retinal pigment epithelial (RPE) cells to oxidative stress. Much oxidative damage is due to hydrogen peroxide meeting redox-active iron in the acidic and reducing lysosomal environment, resulting in the production of toxic hydroxyl radicals that may oxidize intralysosomal content, leading to lipofuscin (LF) formation or, if more extensive, to permeabilization of lysosomal membranes. Formation of LF is a risk factor for age-related macular degeneration (AMD) and known to jeopardize normal autophagic rejuvenation of vital cellular biomolecules. Lysosomal membrane permeabilization causes release of lysosomal content (redox-active iron, lytic enzymes), which may then cause cell death. Total cellular and lysosomal low-mass iron of cultured, immortalized human RPE (ARPE-19) cells was compared to that of another professional scavenger cell line, J774, using atomic absorption spectroscopy and the cytochemical sulfide-silver method (SSM). It was found that both cell lines contained comparable levels of total as well as intralysosomal iron, suggesting that the latter is mainly kept in a non-redox-active state in ARPE-19 cells. Basal levels and capacity for upregulation of the iron-binding proteins ferritin, metallothionein and heat shock protein 70 were tested in both cell lines using immunoblotting. Compared to J774 cells, ARPE-19 cells were found to contain very high basal levels of all these proteins, which could be even further upregulated following appropriate stimulation. These findings suggest that a high basal expression of iron-binding stress proteins, which during their normal autophagic turnover in lysosomes may temporarily bind iron prior to their degradation, could contribute to the unusual oxidative stress-resistance of ARPE-19 cells. A high steady state influx of such proteins into lysosomes would keep the level of lysosomal redox-active iron permanently low. This, in turn, should delay intralysosomal accumulation of LF in RPE cells, which is known to reduce autophagic turnover as well as uptake and degradation of worn out photoreceptor tips. This may explain why severe LF accumulation and AMD normally do not develop until fairly late in life, in spite of RPE cells being continuously exposed to high levels of oxygen and light, as well as large amounts of lipid-rich material.

  • 27.
    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, p. 162-177Article 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.

  • 28.
    Koulikovska, Marina
    et al.
    Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Rafat, Mehrdad
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. LinkoCare Life Sciences AB, Linköping, Sweden.
    Petrovski, Goran
    University of Debrecen, Debrecen, Hungary; University of Szeged, Szeged, Hungary.
    Veréb, Zoltán
    University of Debrecen, Debrecen, Hungary; University of Szeged, Szeged, Hungary.
    Akhtar, Saeed
    Department of Optometry, College of Applied Medicine, King Saud University, Riyadh, Saudi Arabia.
    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.
    Enhanced Regeneration of Corneal Tissue Via a Bioengineered Collagen Construct Implanted by a Nondisruptive Surgical Technique2015In: Tissue Engineering. Part A, ISSN 1937-3341, E-ISSN 1937-335X, Vol. 21, no 5-6, p. 1116-1130Article in journal (Refereed)
    Abstract [en]

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

  • 29.
    Kozak Ljunggren, Monika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Elizondo, Rodolfo A.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Edin, Joel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Olsen, David
    FibroGen Incorporated, San Francisco, CA, USA.
    Merrett, Kimberley
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Ottawa Hospital Research Institute–Vision Programme, Ottawa, Ontario, Canada.
    Lee, Chang-Jang
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Ottawa Hospital Research Institute–Vision Programme, Ottawa, Ontario, Canada.
    Salerud, Göran
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Polarek, James
    FibroGen Incorporated, San Francisco, CA, USA.
    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.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Effect of Surgical Technique on Corneal Implant Performance2014In: Translational Vision Science & Technology, ISSN 2164-2591, Vol. 3, no 2, p. 1-13Article in journal (Refereed)
    Abstract [en]

    Purpose: Our aim was to determine the effect of a surgical technique on biomaterial implant performance, specifically graft retention.

     

    Methods: Twelve mini pigs were implanted with cell-free, 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) cross-linked recombinant human collagen type III (RHCIII) hydrogels as substitutes for donor corneal allografts using overlying sutures with or without human amniotic membrane (HAM) versus interrupted sutures with HAM. The effects of the retention method were compared as well as the effects of collagen concentration (13.7% to 15% RHCIII).

    Results: All implanted corneas showed initial haze that cleared with time, resulting in corneas with optical clarity matching those of untreated controls. Biochemical analysis showed that by 12 months post operation, the initial RHCIII implants had been completely remodeled, as type I collagen, was the major collagenous protein detected, whereas no RHCIII could be detected. Histological analysis showed all implanted corneas exhibited regeneration of epithelial and stromal layers as well as nerves, along with touch sensitivity and tear production. Most neovascularization was seen in corneas stabilized by interrupted sutures.

    Conclusions: This showed that the surgical technique used does have a significant effect on the overall performance of corneal implants, overlying sutures caused less vascularization than interrupted sutures.

    Translational Relevance: Understanding the significance of the suturing technique can aid the selection of the most appropriate procedure when implanting artificial corneal substitutes. The same degree of regeneration, despite a higher collagen content indicates that future material development can progress toward stronger, more resistant implants.

  • 30.
    Lagali, Neil
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Bourghardt Peebo, Beatrice
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Germundsson, Johan
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Edén, Ulla
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Danyali, Reza
    Linköping University, Faculty of Health Sciences.
    Rinaldo, Marcus
    Linköping University, Faculty of Health Sciences.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Laser-Scanning in vivo Confocal Microscopy of the Cornea: Imaging and Analysis Methods for Preclinical and Clinical Applications2013In: Confocal Laser Microscopy: Principles and Applications in Medicine, Biology, and the Food Sciences, INTECH, 2013Chapter in book (Other academic)
  • 31.
    Lagali, Neil
    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.
    Edén, Ulla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Paaske Utheim, Tor
    Oslo University Hospital, Norway.
    Chen, Xiangjun
    Synslaser Kirurgi AS, Norway.
    Riise, Ruth
    Innland Hospital, Norway.
    Delby, Anette
    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.
    In Vivo Morphology of the Limbal Palisades of Vogt Correlates With Progressive Stem Cell Deficiency in Aniridia-Related Keratopathy2013In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 54, no 8, p. 5333-5342Article in journal (Refereed)
    Abstract [en]

    Purpose. To investigate morphologic alterations in the limbal palisades of Vogt in a progressive form of limbal stem cell deficiency.

    Methods. Twenty Norwegian subjects (40 eyes) with congenital aniridia and 9 healthy family members (18 eyes) without aniridia were examined. Clinical grade of aniridia-related keratopathy (ARK) was assessed by slit-lamp biomicroscopy, and tear production and quality, corneal thickness, and sensitivity were additionally measured. The superior and inferior limbal palisades of Vogt and central cornea were examined by laser scanning in vivo confocal microscopy (IVCM).

    Results. In an aniridia patient with grade 0 ARK, a transparent cornea and normal limbal palisade morphology were found. In grade 1 ARK, 5 of 12 eyes had degraded palisade structures. In the remaining grade 1 eyes and in all 20 eyes with stage 2, 3, and 4 ARK, palisade structures were absent by IVCM. Increasing ARK grade significantly correlated with reduced visual acuity and corneal sensitivity, increased corneal thickness, degree of degradation of superior and inferior palisade structures, reduced peripheral nerves, increased inflammatory cell invasion, and reduced density of basal epithelial cells and central subbasal nerves. Moreover, limbal basal epithelial cell density and central corneal subbasal nerve density were both significantly reduced in aniridia compared to healthy corneas (P = 0.002 and 0.003, respectively).

    Conclusions. Progression of limbal stem cell deficiency in aniridia correlates with degradation of palisade structures, gradual transformation of epithelial phenotype, onset of inflammation, and a corneal nerve deficit. IVCM can be useful in monitoring early- to late-stage degenerative changes in stem cell–deficient patients.

  • 32.
    Mirabelli, Pierfrancesco
    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.
    Bourghardt Peebo, Beatrice
    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.
    Xeroudaki, Maria
    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.
    Koulikovska, Marina
    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.
    Early effects of dexamethasone and anti-VEGF therapy in an inflammatory corneal neovascularization model2014In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 125, p. 118-127Article in journal (Refereed)
    Abstract [en]

    Inflammatory angiogenesis is the pathogenic mechanism of various sight-threatening eye diseases, among them corneal neovascularization. Current treatment options include steroids which have undesirable side effects, or anti-VEGF which has only limited efficacy. In an inflammatory environment, however, angiogenesis can be stimulated by numerous factors not directly targeted by anti-VEGF therapy. The aim of this study was to induce corneal inflammation leading to angiogenesis, and investigate the early, differential effects of steroid and anti-VEGF therapy at the cellular, tissue, and gene expression levels. Fifty-two Wistar rats received a single intrastromal corneal suture to induce a controlled inflammatory angiogenic response. Rats were subsequently treated with dexamethasone, rat specific anti-VEGF, or goat IgG (control), topically 4 times daily for 7 days. In vivo confocal microscopy of the cornea was performed longitudinally from 5 h up to 7 d to investigate morphology at the cellular and tissue-level. In vivo photographic vessel analysis and immunohistochemistry were also performed. RT-PCR for VEGF-A, FGF-2, IL-6, TNF-alpha, CXCL2, CCL2, CCL3 and DLL4 was performed at 24 h, and for VEGF-A, IL-6, TNF-alpha, FGF-2, CXCL2, CCL2, and CCL3 at 7 days. Early infiltration of CD11b + myeloid cells into the cornea at 5 h post-suture was delayed by both treatments relative to controls; however neither treatment was able to suppress accumulation of myeloid cells at day 2 or 7. Limbal vessel dilation was inhibited at 5 h by both treatments, but only dexamethasone showed sustained effect until day 2. Early macrophage recruitment was also suppressed by dexamethasone (but not by anti-VEGF) until day 2. Dexamethasone furthermore suppressed corneal neovascularization at day 7 by over 90%, whereas suppression by anti-VEGF was 14%. Despite differential suppression of vessel dilation, macrophage recruitment, and vascular invasion, anti-VEGF and dexamethasone both down-regulated VEGF-A and IL-6 expression at 24 h with sustained effect to 7 d. They also both down regulated FGF-2 and TNF-alpha at 24 h and CCL2 at 7 d. In conclusion, anti-angiogenic treatments influence early, pre-angiogenic tissue activity such as limbal vessel dilation, inflammatory cell infiltration of the stroma, and macrophage recruitment. Importantly, the differential effects of steroids and anti-VEGF treatment in suppressing neovascular growth could not be attributed to differential inhibition of several major angiogenic and inflammatory factors in the early pre-sprouting phase, including IL-6, VEGF-A, FGF-2, TNF-alpha, CCL2, CCL3, CXCL2, or DLL4.

  • 33.
    Parissi, Marlen
    et al.
    Oslo University Hospital, Norway.
    Karanis, Georgios
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Randjelovic, Stefan
    Norwegian Dry Eye Clin, Norway.
    Germundsson, Johan
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Poletti, Enea
    University of Padua, Italy.
    Ruggeri, Alfredo
    University of Padua, Italy.
    Paaske Utheim, Tor
    Oslo University Hospital, Norway.
    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.
    Standardized Baseline Human Corneal Subbasal Nerve Density for Clinical Investigations With Laser-Scanning in Vivo Confocal Microscopy2013In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 54, no 10, p. 7091-7102Article in journal (Refereed)
    Abstract [en]

    Purpose. We established a baseline value for central corneal subbasal nerve density in a large, healthy cohort.

    Methods. A total of 106 healthy volunteers (207 eyes) underwent full ophthalmic examination, including laser-scanning in vivo confocal microscopy (IVCM) of the central cornea. Images of the corneal subbasal nerve plexus were acquired and analyzed based on defined criteria. Nerve tracing was performed by two human observers and by a fully automated method. Subbasal nerve density was stratified by eye, observer, tracing method, calculation method, and age group. Association of nerve density with age was examined by linear regression and population distribution was examined by nonlinear regression.

    Results. We analyzed 892 distinct, high quality images of the subbasal nerve plexus (mean, 4.3 images/eye) from 207 eyes. An overall mean central subbasal nerve density of 19 mm/mm2 was found in 106 subjects aged 15 to 88 years, independent of eye, sex, or nerve tracing method, while the SD was a consistent 4 to 5 mm/mm2. Subbasal nerve density followed a normal Gaussian distribution, and correlated negatively with age, with a mean decline of 0.25% to 0.30% per year, independent of eye, observer, or nerve tracing method. Moreover, the use of automated tracing techniques and randomized sampling may improve the speed and reproducibility of subbasal nerve density assessment for clinical applications.

    Conclusions. A baseline human corneal subbasal nerve density has been determined by laser-scanning IVCM using rigorous methods. The methods and results could aid in the future assessment of corneal nerves in various patient populations.

  • 34.
    Rafat, Mehrdad
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. 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.
    Merret, K,
    Linköping University, Department of Clinical and Experimental Medicine. 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.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Collagen-based bioengineered corneas: a material development update2011Conference paper (Other academic)
    Abstract [en]

    Purpose

    Our overall objective is to develop novel biomimetic materials that support the regeneration of diseased or damaged corneal tissue. This presentation will provide an update on such materials developed in our group.

    Methods

    We have developed a range of collagen-based materials as mimics of the cell-free corneal stromal extracellular matrix. Promising material formulations were tested pre-clinically for their physical properties (e.g. mechanical, optical, water uptake, etc.) and physiological properties (e.g. interactions with corneal cells, biodegradation, in vivo implantation in animals etc.). One of the early formulations was clinically tested in the corneas of 10 patients, results of which will be discussed.

    Results

    More recently, our team of Canadian and Swedish researchers reported the successful implantation of cell-free, bioengineered corneas into patients with keratoconus and central scarring in a Phase 1 clinical trial. These implants acted as stable scaffolds that promoted functional regeneration of corneal cells and nerves. At 24 months post-operative, six of the ten patients could see four times further than before the operation. With the help of rigid contact lenses – the results in all ten patients were similar to what the traditional corneal transplant with human donor tissue would be, with one patient achieving 20/20 vision and two others with 20/25 vision.

    Conclusions

    Despite the promising clinical results, more robust and elastic materials are required to withstand the adverse host conditions faced for high risk transplantation in severely damaged or diseased corneas as well as for full-thickness corneal implants. Examples of next generation biomaterials that have been implanted into animal models as partial and full-thickness grafts that allow regeneration of nerve sub-types and show resistance to neovascularization will be shown.

  • 35.
    Rafat, Mehrdad
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Arts and Sciences.
    Hackett, Joanne
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation 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.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Artificial Cornea2011In: Ocular Periphery and Disorders / [ed] Darlene A. Dartt, Peter Bex, Patricia D'Amore, Reza Dana, Linda Mcloon, Jerry Niederkorn, Elsevier, 2011, p. 311-317Chapter in book (Other academic)
    Abstract [en]

    This selection of articles from the Encyclopedia of the Eye is the first single-volume overview presenting articles on the function, biology, physiology, and pathology of the structures of the ocular periphery, as well as the related disorders and their treatment. The peripheral structures are implicated in a number of important diseases, including optic neuritis, thyroid eye disease, and strabismus. The volume offers a basic science background of these topics rather than a strictly clinical focus.

    *The first single volume to integrate comparative studies into a comprehensive resource on the neuroscience of the ocular periphery

    *Chapters are carefully selected from the Encyclopedia of the Eye by the world's leading vision researchers

    *The best researchers in the field provide their conclusions in the context of the latest experimental results

  • 36.
    Rafat, Mehrdad
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. 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.
    Koulikovska, Marina
    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.
    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.
    Development of a Highly Elastic Bioengineered Cornea: From Research to Commercialization2013Conference paper (Other academic)
    Abstract [en]

    Background: Despite the promising clinical results that we previously reported on biosynthetic corneas, more elastic materials are required for surgical manipulation and withstanding the adverse host conditions faced by high risk corneal transplants.

    Purpose: The overall objective was to develop novel bioengineered materials that can replace the damaged corneal tissue. Another objective was to evaluate the in vivo integration of the materials in rabbit models using a femtosecond laser intrastromal surgical technique.

    Methods: Bioengineered corneas were prepared using porcine collagen cross-linked by carbodiimides at various compositions and pH. Promising formulations were tested for their mechanical, optical, and enzymatic and thermal degradation properties as well as for interactions with corneal cells, and in vivo implantation in rabbit’s eyes. A femtosecond laser was used to cut 100 mircon thick discs of mid-stromal tissue from corneas of 15 rabbits and replaced with the bioengineered materials.

    Results: The new material demonstrated improved mechanical properties while maintaining its clarity and biocompatibility. The bioengineered implant retained its shape, thickness, and clarity 8 weeks post-surgery in rabbits.  

    Conclusions: The bioengineered cornea developed in this work has the potential to be used and commercialized as corneal implants to replace the damaged tissue or for corrective surgery applications.

  • 37.
    Rafat, Mehrdad
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. 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.
    Koulikovska, Marina
    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.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. 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.
    In vivo integrity of intra‐corneal bioengineered discs in rabbit models2013In: Acta Ophthalmologica; Special Issue: Abstracts from the 2013 European Association for Vision and Eye Research Conference, August 2013 Volume 91, Issue Supplement s252, John Wiley & Sons, 2013Conference paper (Other academic)
    Abstract [en]

    Background: We have previously reported the successful integration and safety of bioengineered materials as corneal substitutes in human models. Despite the promising results as corneal implants, more elastic and robust materials are required for use as thin intra-corneal lenses to withstand surgical manipulation for corrective surgery and improved vision. Most of the existing corneal inlays are made of synthetic materials. Here we describe the potential of bioengineerd materials for vision correction. Objectives: to develop bioengineered materials as inlays within the corneal tissue as well as evaluating the in vivo integrity and integration of the materials in rabbit models. Methods: Bioengineered inlays were prepared from collagen and tested for their physical and biological propertis. A femtosecond laser was used to cut 100 mircon thick discs of mid-stromal tissue from corneas of 20 rabbits and replaced with bioengineered inlays. Results: The new materials demonstrated improved mechanical properties while maintaining their clarity and biocompatibility. The bioengineered inlays retained their shapes, thickness, and clarity 8 weeks post-surgery in rabbits.

  • 38.
    Rafat, Mehrdad
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Xeroudaki, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Koulikovska, Marina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Sherrell, Peter
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Groth, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Composite core-and-skirt collagen hydrogels with differential degradation for corneal therapeutic applications2016In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 83, p. 142-155Article in journal (Refereed)
    Abstract [en]

    Scarcity of donor tissue to treat corneal blindness and the need to deliver stem cells or pharmacologic agents to ensure corneal graft survival are major challenges. Here, new composite collagen-based hydrogels are developed as implants to restore corneal transparency while serving as a possible reservoir for cells and drugs. The composite hydrogels have a centrally transparent core and embedded peripheral skirt of adjustable transparency and degradability, with the skirt exhibiting faster degradation in vitro. Both core and skirt supported human epithelial cell populations in vitro and the skirt merged homogeneously with the core material to smoothly distribute a mechanical load in vitro. After in vivo transplantation in rabbit corneas over three months, composites maintained overall corneal shape and integrity, while skirt degradation could be tracked in vivo and non-invasively due to partial opacity. Skirt degradation was associated with partial collagen breakdown, thinning, and migration of host stromal cells and macrophages, while the central core maintained integrity and transparency as host cells migrated and nerves regenerated.

    IMPACT:

    This study indicates the feasibility of a collagen-based composite hydrogel to maintain corneal stability and transparency while providing a degradable peripheral reservoir for cell or substance release.

  • 39.
    Rydzanicz, Malgorzata
    et al.
    Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
    Nath, Swapan K
    Arthritis and Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
    Sun, Celi
    Arthritis and Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
    Podfigurna-Musielak, Monika
    Department of Ophthalmology, Leszno Hospital, Leszno, Poland.
    Frajdenberg, Agata
    Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Mrugacz, Malgorzata
    Department of Pediatric Ophthalmology, Medical University of Bialystok, Bialystok, Poland.
    Winters, Daniel
    School of Molecular Biosciences, Washington State University, Spokane, WA, USA.
    Ratnamala, Uppala
    Department of Surgery-Transplant, University of Nebraska Medical Center, Omaha, NE, USA.
    Radhakrishna, Uppala
    Department of Surgery-Transplant, University of Nebraska Medical Center, Omaha, NE, USA.
    Bejjani, Bassem A
    Signature Genomic Laboratories, LLC, Spokane, WA, USA.
    Gajecka, Marzena
    Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
    Identification of novel suggestive loci for high-grade myopia in Polish families2011In: Molecular Vision, ISSN 1090-0535, E-ISSN 1090-0535, Vol. 17, no 221, p. 2028-2039Article in journal (Refereed)
    Abstract [en]

    urpose: Myopia is the most common human eye disorder with complex genetic and environmental causes. To date, several myopia loci have been identified in families of different geographic origin. However, no causative gene(s) have yet been identified. The aim of this study was the characterization of Polish families with high-grade myopia, including genetic analysis. less thanbrgreater than less thanbrgreater thanMethods: Forty-two multiplex Polish families with non-syndromic high-grade myopia participated in the study. All family members underwent detailed ophthalmic examination and high-grade myopia was defined as andlt;=-6.0 diopters (D) based on the spherical refractive error. A genome-wide single nucleotide polymorphism (SNP)-based high-density linkage scan was performed using Affymetrix Human SNP Array 6.0 on a selected family (HM-32) with multiple affected individuals. less thanbrgreater than less thanbrgreater thanResults: Nonparametric linkage analysis identified three novel loci in family HM-32 at chromosome 7p22.1-7p21.1 ([NPL] 8.26; p = 0.006), chromosome 7p12.3-7p11.2 ([NPL] 8.23; p = 0.006), and chromosome 12p12.3-12p12.1 ([NPL] 8.02; p = 0.006), respectively. The effect of linkage disequilibrium on linkage due to dense SNP map was addressed by systematically pruning SNPs from the linkage panel. less thanbrgreater than less thanbrgreater thanConclusions: Haplotype analysis with informative crossovers in affected individuals defined a 12.2; 10.9; and 9.5 Mb genomic regions for high-grade myopia spanned between SNP markers rs11977885/rs10950639, rs11770622/rs9719399, and rs4763417/rs10842388 on chromosomes 7p22.1-7p21.1, 7p12.3-7p11.2, and 12p12.3-12p12.1, respectively.

  • 40.
    Rydzanicz, Malgorzata
    et al.
    Polish Academy of Science.
    Nowak, Dorota M
    Polish Academy of Science.
    Karolak, Justyna A
    Polish Academy of Science.
    Frajdenberg, Agata
    Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Podfigurna-Musielak, Monika
    Leszno Hospital.
    Mrugacz, Malgorzata
    University of Medical Science, Bialystok.
    Gajecka, Marzena
    Polish Academy of Science.
    IGF-1 gene polymorphisms in Polish families with high-grade myopia2011In: Molecular Vision, ISSN 1090-0535, E-ISSN 1090-0535, Vol. 17, no 264-65, p. 2428-2439Article in journal (Refereed)
    Abstract [en]

    Purpose: Recent work has suggested that insulin-like growth factor 1 (IGF-1) gene polymorphisms are genetically linked with high-grade myopia (HM), which is a complex-trait eye disorder in which numerous candidate loci and genes are thought to play a role. We investigated whether the IGF-1 single nucleotide polymorphisms (SNPs) rs6214, rs10860860, and rs2946834 are associated with HM (andlt;=-6.0 diopters [D]) and any myopia (andlt;=-0.5 D) phenotype in Polish families. less thanbrgreater than less thanbrgreater thanMethods: Forty-two multiplex HM Polish families, of whom 127 had HM, participated in the study. All of the family members (n=306) underwent a detailed ophthalmic examination, including axial length measurements. The IGF-1 SNPs rs6214, rs10860860, and rs2946834 were evaluated by PCR-RFLP and direct sequencing methods. Both Family-Based Association Test (FBAT) and family-based Pedigree Disequilibrium Test (PDT) were used to examine the potential association of the IGF-1 SNPs rs6214, rs10860860, and rs2946834 with HM or any myopia. To determine the distribution of the HM-associated SNPs rs6214 and rs10860860, 543 unrelated individuals from the general Polish population were also analyzed. less thanbrgreater than less thanbrgreater thanResults: We found no significant association between the IGF-1 SNPs rs6214, rs10860860, and rs2946834 and HM or any myopia phenotype in Polish HM families. In the general Polish population, the minor allele frequencies of the SNPs rs6214 and rs10860860 did not deviate significantly from the distribution reported for European populations (p=0.629). In the FBAT analysis under the dominant model, the haplotype consisted of T allele of rs10860860, with C allele of rs2946834 of IGF-1 was found less frequently transmitted to HM individuals (p=0.0065), pointing to a nonassociated or protective haplotype. less thanbrgreater than less thanbrgreater thanConclusions: Our results do not support recent studies reporting an association of the SNPs rs6214, rs10860860, and rs2946834 in the IGF-1 gene with HM and any myopia phenotypes. Further replication studies involving other populations are needed to investigate the possible role of IGF-1 as a potential myopia candidate gene.

  • 41.
    Wiklund, Anna
    et al.
    Karolinska Institutet, Institutionen för klinisk neurovetenskap,.
    Bourghardt Peebo, Beatrice
    Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    ACUTE EXUDATIVE POLYMORPHOUS VITELLIFORM MACULOPATHY IN A YOUNG WOMAN: PRESYMPTOMATIC FINDINGS AND 21-MONTH FOLLOW-UP2013In: RETINAL Cases & Brief Reports, ISSN 1935-1089, Vol. 7, no 2, p. 123-127Article in journal (Refereed)
    Abstract [en]

    Purpose: To describe ocular findings before and after the diagnosis of acute exudative polymorphous vitelliform maculopathy, in an otherwise healthy 28-year-old woman.

    Methods: Case report with 21-months of follow-up. Fundus photography, optical coherence tomography, fluorescein angiography, indocyanine green angiography, and autofluorescence were used for imaging the retina. To examine retinal function, full-field electroretinogram, multifocal electroretinogram, electrooculography, and dark adaptometry were performed. Genetic analysis for mutations associated with Best disease was done.

    Results: In the asymptomatic patient before diagnosis, white-yellow, drusen-like, subretinal depositions were found in both eyes. A few months later, the patient developed bilateral visual disturbances. Retinal examination at the acute phase revealed a characteristic pattern of multifocal white-yellow subretinal lesions in both posterior poles, imaged by ophthalmoscopy, fluorescein angiography, indocyanine green angiography, and optical coherence tomography. Additionally, electrooculography and dark adaptometry were abnormal. Full-field electroretinogram was normal, but multifocal electroretinogram revealed central depression of peak amplitudes. During the 21-month follow-up without any treatment, visual acuity recovered, electrooculography and dark adaptometry normalized, and the patient experienced one episode of relapse. Genetic studies excluded mutations in the bestrophin gene (BEST1).

    Conclusion: Acute exudative polymorphous vitelliform maculopathy is still a condition of unknown origin, primarily affecting the pigment epithelium. Earlier reports have discussed whether the condition is inherited or acquired. In this report, the presymptomatic retinal findings in acute exudative polymorphous vitelliform maculopathy are described for the first time, indicating that a condition may be associated with primarily affected retinal pigment epithelium.

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