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  • 51.
    Mukwaya, Anthonny
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Mirabelli, Pierfrancesco
    Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Lennikov, Anton
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Univ Missouri, MO USA.
    Thangavelu, Muthukumar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Chonbuk Natl Univ, South Korea.
    Jensen, Lasse
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi.
    Peebo, Beatrice
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Lagali, Neil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM. Sorlandet Hosp Arendal, Norway.
    Repeat Corneal Neovascularization is Characterized by More Aggressive Inflammation and Vessel Invasion Than in the Initial Phase2019Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 60, nr 8, s. 2990-3001Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Treatment of corneal neovascularization can lead to vessel regression and recovery of corneal transparency. Here, we examined the response of the cornea to a repeated stimulus after initial vessel regression comparing the second wave of neovascularization with the first.

    Methods: Corneal neovascularization was induced by surgical suture placement in the rat cornea for 7 days, followed by suture removal and a 30-day regression period. Corneas were then re-sutured and examined for an additional 4 days. Longitudinal slit-lamp imaging, in vivo confocal microscopy, and microarray analysis of global gene expression was conducted to assess the inflammatory and neovascularization response. Inhibitory effect of topical dexamethasone for repeat neovascularization was assessed.

    Results: After initial robust neovascularization, 30 days of regression resulted in the recovery of corneal transparency; however, a population of barely functional persistent vessels remained at the microscopic level. Upon re-stimulation, inflammatory cell invasion, persistent vessel dilation, vascular invasion, and gene expression of VegfaIl1βIl6Ccl2Ccl3, and Cxcl2 all doubled relative to initial neovascularization. Repeat neovascularization occurred twice as rapidly as initially, with activation of nitric oxide and reactive oxygen species, matrix metalloproteinase, and leukocyte extravasation signaling pathways, and suppression of anti-inflammatory LXR/RXR signaling. While inhibiting initial neovascularization, a similar treatment course of dexamethasone did not suppress repeat neovascularization.

    Conclusions: Persistent vessels remaining after the initial resolution of neovascularization can rapidly reactivate to facilitate more aggressive inflammation and repeat neovascularization, highlighting the importance of achieving and confirming complete vessel regression after an initial episode of corneal neovascularization.

  • 52.
    Mukwaya, Anthony
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Lennikov, Anton
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Xeroudaki, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Mirabelli, Pierfrancesco
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Lachota, Mieszko
    Department of Immunology, Medical University of Warsaw, Warsaw, Poland.
    Jensen, Lasse
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi.
    Peebo, Beatrice
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Lagali, Neil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Time-dependent LXR/RXR pathway modulation characterizes capillary remodeling in inflammatory corneal neovascularization2018Ingår i: Angiogenesis, ISSN 0969-6970, E-ISSN 1573-7209, Vol. 21, nr 2, s. 395-413Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 53.
    Mukwaya, Anthony
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Lindvall, Jessica M.
    Stockholm University, Sweden.
    Xeroudaki, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Peebo, Beatrice
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Ali, Zaheer
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Lennikov, Anton
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Jensen, Lasse
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi. Karolinska Institute, Sweden.
    Lagali, Neil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    A microarray whole-genome gene expression dataset in a rat model of inflammatory corneal angiogenesis2016Ingår i: Scientific Data, E-ISSN 2052-4463, Vol. 3, artikel-id UNSP 160103Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In angiogenesis with concurrent inflammation, many pathways are activated, some linked to VEGF and others largely VEGF-independent. Pathways involving inflammatory mediators, chemokines, and micro-RNAs may play important roles in maintaining a pro-angiogenic environment or mediating angiogenic regression. Here, we describe a gene expression dataset to facilitate exploration of pro-angiogenic, pro-inflammatory, and remodelling/normalization-associated genes during both an active capillary sprouting phase, and in the restoration of an avascular phenotype. The dataset was generated by microarray analysis of the whole transcriptome in a rat model of suture-induced inflammatory corneal neovascularisation. Regions of active capillary sprout growth or regression in the cornea were harvested and total RNA extracted from four biological replicates per group. High quality RNA was obtained for gene expression analysis using microarrays. Fold change of selected genes was validated by qPCR, and protein expression was evaluated by immunohistochemistry. We provide a gene expression dataset that may be re-used to investigate corneal neovascularisation, and may also have implications in other contexts of inflammation-mediated angiogenesis.

  • 54.
    Mukwaya, Anthony
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Mirabelli, Pierfrancesco
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Lennikov, Anton
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Xeroudaki, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Schaupper, Mira
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Peebo, Beatrice
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Lagali, Neil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Genome-wide expression datasets of anti-VEGF and dexamethasone treatment of angiogenesis in the rat cornea2017Ingår i: Scientific Data, E-ISSN 2052-4463, Vol. 4, artikel-id 170111Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Therapeutics against pathologic new blood vessel growth, particularly those targeting vascular endothelial growth factor (VEGF) are of enormous clinical interest. In the eye, where anti-VEGF agents are in widespread clinical use for treating retinal and corneal blindness, only partial or transient efficacy and resistance to anti-VEGF agents are among the major drawbacks. Conversely, corticosteroids have long been used in ophthalmology for their potency in suppressing inflammation and angiogenesis, but their broad biological activity can give rise to side effects such as glaucoma and cataract. To aid in the search for more targeted and effective anti-angiogenic therapies in the eye, we present here a dataset comparing gene expression changes in dexamethasone versus anti-Vegfa treatment of inflammation leading to angiogenesis in the rat cornea. Global gene expression analysis with GeneChip Rat 230 2.0 microarrays was conducted and the metadata submitted to Expression Omnibus repository. Here, we present a high-quality validated dataset enabling genome-wide comparison of genes differentially targeted by dexamethasone and anti-Vegf treatments, to identify potential alternative therapeutic targets for evaluation.

  • 55.
    Mukwaya, Anthony
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Peebo, Beatrice
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Xeroudaki, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Ali, Zaheer
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Lennikov, Anton
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Jensen, Lasse
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi.
    Lagali, Neil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Factors regulating capillary remodeling in a reversible model of inflammatory corneal angiogenesis2016Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, s. 1-15, artikel-id 32137Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Newly formed microcapillary networks arising in adult organisms by angiogenic and inflammatory stimuli contribute to pathologies such as corneal and retinal blindness, tumor growth, and metastasis. Therapeutic inhibition of pathologic angiogenesis has focused on targeting the VEGF pathway, while comparatively little attention has been given to remodeling of the new microcapillaries into a stabilized, functional, and persistent vascular network. Here, we used a novel reversible model of inflammatory angiogenesis in the rat cornea to investigate endogenous factors rapidly invoked to remodel, normalize and regress microcapillaries as part of the natural response to regain corneal avascularity. Rapid reversal of an inflammatory angiogenic stimulus suppressed granulocytic activity, enhanced recruitment of remodelling macrophages, induced capillary intussusception, and enriched pathways and processes involving immune cells, chemokines, morphogenesis, axonal guidance, and cell motility, adhesion, and cytoskeletal functions. Whole transcriptome gene expression analysis revealed suppression of numerous inflammatory and angiogenic factors and enhancement of endogenous inhibitors. Many of the identified genes function independently of VEGF and represent potentially new targets for molecular control of the critical process of microvascular remodeling and regression in the cornea.

  • 56.
    Muthukumar, T.
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Sreekumar, G.
    Dept. of Biotechnology, St.Josephs College of Engineering, Sholinganallur, Tamilnadu, India.
    Sastry, T. P.
    Formerly Bio products laboratory, Central Leather Research Institute, Adyar, Tamilnadu, India.
    Chamundeeswari, M.
    Dept. of Biotechnology, St.Josephs College of Engineering, Sholinganallur, Tamilnadu, India.
    COLLAGEN AS A POTENTIAL BIOMATERIAL IN BIOMEDICAL APPLICATIONS2018Ingår i: Reviews on Advanced Materials Science, ISSN 1606-5131, E-ISSN 1605-8127, Vol. 53, nr 1, s. 29-39Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Collagen, a biopolymer finds its application in the preparation of pharmaceutical products that are used in wound management, ophthalmic, orthopaedic and oral surgeries. This wide applicability is due its special properties such as biodegradability, biocompatibility, easy availability and high versatility. Collagen is isolated from various sources such as bovine skin, fish skin, chicken skin, skin waste of marine organisms, solid wastes of leather industry, short tendons of slaughtered cattle and bone. The isolated collagen from biological wastes is found to be cost effective due to the adaptation of simple methods for its isolation when compared with other commercially available biological macromolecules. The functional groups such as amino and carboxylic acid present in collagen helps in its modification that suits for various end uses which include wound healing, ophthalmic defects, drug delivery and tissue engineering applications. These beneficial properties impart uniqueness to collagen molecule among the available bio molecules.

  • 57.
    Ong, Jeb A.
    et al.
    Maisonneuve Rosemt Hospital, Canada; University of Montreal, Canada.
    Auvinet, Edouard
    University of Montreal, Canada.
    Forget, Karolyn J.
    Maisonneuve Rosemt Hospital, Canada.
    Lagali, Neil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Fagerholm, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Maisonneuve Rosemt Hospital, Canada.
    Meunier, Jean
    University of Montreal, Canada; University of Montreal, Canada.
    Brunette, Isabelle
    Maisonneuve Rosemt Hospital, Canada; University of Montreal, Canada.
    3D Corneal Shape After Implantation of a Biosynthetic Corneal Stromal Substitute2016Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, nr 6, s. 2355-2365Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE. The current and projected shortage of transplantable human donor corneas has prompted the development of long-term alternatives to human donor tissue for corneal replacement. The biosynthetic stromal substitutes (BSS) characterized herein represent a potentially safe alternative to donor organ transplantation for anterior corneal stromal diseases. The goal of this phase 1 safety study was to characterize the three-dimensional (3D) corneal shape of the first 10 human patients implanted with a BSS and assess its stability over time. METHODS. Ten patients underwent anterior lamellar keratoplasty using a biosynthetic corneal stromal implant for either advanced keratoconus or central corneal scarring. Surgeries were performed at Linkoping University Hospital, between October and November 2007. Serial corneal topographies were performed on all eyes up to a 4-year follow-up when possible. Three-dimensional shape average maps were constructed for the 10 BSS corneas and for 10 healthy controls. Average 3D shape corneal elevation maps, difference maps, and statistics maps were generated. RESULTS. The biosynthetic stromal substitutes implants remained stably integrated into the host corneas over the 4-year follow-up period, without signs of wound dehiscence or implant extrusion. The biosynthetic stromal substitutes corneas showed steeper surface curvatures and were more irregular than the healthy controls. CONCLUSIONS. Corneal astigmatism and surface steepness were observed 4 years after BSS implantation, while the implants remained stably integrated in the host corneas. Future studies will indicate if biomaterials technology will allow for the optimization of postoperative surface irregularity after anterior stromal replacement, a new window of opportunity that is not available with traditional corneal transplantation techniques.

  • 58.
    Parissi, Marlen
    et al.
    University of Oslo, Norway; Norwegian Dry Eye Clin, Norway.
    Randjelovic, Stefan
    Norwegian Dry Eye Clin, Norway.
    Poletti, Enea
    University of Padua, Italy.
    Guimaraes, Pedro
    University of Padua, Italy.
    Ruggeri, Alfredo
    University of Padua, Italy.
    Fragkiskou, Sofia
    Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM. Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Ba Wihlmark, Thu
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Paaske Utheim, Tor
    University of Oslo, Norway; Norwegian Dry Eye Clin, Norway; University of Oslo, Norway.
    Lagali, Neil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Corneal Nerve Regeneration After Collagen Cross-Linking Treatment of Keratoconus A 5-Year Longitudinal Study2016Ingår i: JAMA ophthalmology, ISSN 2168-6165, E-ISSN 2168-6173, Vol. 134, nr 1, s. 70-78Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    IMPORTANCE It is unknown whether a neurotrophic deficit or pathologic nerve morphology persists in keratoconus in the long term after corneal collagen cross-linking (CXL) treatment. Nerve pathology could impact long-term corneal status in patients with keratoconus. OBJECTIVE To determine whether CXL treatment of keratoconus results in normalization of subbasal nerve density and architecture up to 5 years after treatment. DESIGN, SETTING, AND PARTICIPANTS Observational study of 19 patients with early-stage keratoconus indicated for a first CXL treatment with longitudinal follow-up to 5 years postoperatively (examinations were performed from 2009 to 2015; analysis was performed from February to May 2015) and 19 age-matched healthy volunteers at a primary care center and a university hospital ophthalmology department. EXPOSURE The patients with keratoconus underwent standard epithelial-off UV-A/riboflavin CXL treatment with 30-minute UV-A exposure at 3mW/cm(2) irradiance. MAIN OUTCOMES AND MEASURES Central corneal subbasal nerve density and subbasal nerve architecture by use of laser-scanning in vivo confocal microscopy; subbasal nerve analysis by 2 masked observers and by use of a fully automated method; wide-field mosaics of subbasal nerve architecture by use of an automated method; and ocular surface touch sensitivity by use of contact esthesiometry. RESULTS Mean (SD) age of the 19 patients with keratoconus was 27.5 (7.1) years (range, 19-44 years), and minimal corneal thickness was 428 (36) mu m (range, 372-497 mu m). Compared with the mean (SD) preoperative subbasal nerve density of 21.0 (4.2) mm/mm(2) in healthy corneas, the mean (SD) preoperative subbasal nerve density of 10.3 (5.6) mm/mm(2) in the corneas of patients with stage 1 or 2 keratoconus was reduced 51%(mean difference, 10.7 mm/mm(2) [95% CI, 6.8-14.6 mm/mm(2)]; P < .001). After CXL, nerves continued to regenerate for up to 5 years, but nerve density remained reduced relative to healthy corneas at final follow-up (mean reduction, 8.5 mm/mm(2) [95% CI, 4.7-12.4 mm/mm(2)]; P < .001) despite recovery of touch sensitivity to normal levels by 6 months. Preoperatively, more frequent nerve loops, crossings, and greater crossing angles were observed in the corneas of patients with keratoconus compared with healthy corneas. Postoperatively, the frequency of nerve looping increased, crossings were more frequent, and nerve tortuosity increased. Wide-field mosaics indicated persistent disrupted orientation of the regenerating subbasal nerves 5 years after CXL. CONCLUSIONS AND RELEVANCE Keratoconus is characterized by a neurotrophic deficit and altered nerve morphology that CXL treatment does not address, despite providing a positive biomechanical effect in the stroma. Given the widespread use of CXL in the management of patients with keratoconus, the progression of abnormal innervation after CXL should be recognized.

  • 59.
    Peterson, M.
    et al.
    Uppsala University, Sweden.
    Pingel, R.
    Uppsala University, Sweden.
    Lagali, Neil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Dahlin, L. B.
    Hand Surg Lund University, Sweden; Skåne University Hospital, Sweden.
    Rolandsson, O.
    Umeå University, Sweden.
    Association between HbA(1c) and peripheral neuropathy in a 10-year follow-up study of people with normal glucose tolerance, impaired glucose tolerance and Type 2 diabetes2017Ingår i: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 34, nr 12, s. 1756-1764Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims To explore the association between HbA(1c) and sural nerve function in a group of people with normal glucose tolerance, impaired glucose tolerance or Type 2 diabetes. Methods We conducted a 10-year follow-up study in 87 out of an original 119 participants. At study commencement (2004), 64 men and 55 women (mean age 61.1 years) with normal glucose tolerance (n=39), impaired glucose tolerance (n=29), or Type 2 diabetes (n=51) were enrolled. At the 2014 follow-up (men, n=46, women, n=41; mean age 71.1 years), 36, nine and 42 participants in the normal glucose tolerance, impaired glucose tolerance and Type 2 diabetes categories, respectively, were re-tested. Biometric data and blood samples were collected, with an electrophysiological examination performed on both occasions. Results At follow-up, we measured the amplitude of the sural nerve in 74 of the 87 participants. The mean amplitude had decreased from 10.9 V (2004) to 7.0 mu V (2014; Pamp;lt;0.001). A 1% increase in HbA(1c) was associated with a similar to 1% average decrease in the amplitude of the sural nerve, irrespective of group classification. Crude and adjusted estimates ranged from -0.84 (95% CI -1.32, -0.37) to -1.25 (95% CI -2.31, -0.18). Although the mean conduction velocity of those measured at both occasions (n=73) decreased from 47.6 m/s to 45.8 m/s (P=0.009), any association with HbA(1c) level was weak. Results were robust with regard to potential confounders and missing data. Conclusions Our data suggest an association between sural nerve amplitude and HbA(1c) at all levels of HbA(1c). Decreased amplitude was more pronounced than was diminished conduction velocity, supporting the notion that axonal degeneration is an earlier and more prominent effect of hyperglycaemia than demyelination.

  • 60.
    Piotr Czajka, Marcin
    et al.
    Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Byhr, Eva
    Sahlgrens University Hospital, Sweden.
    Olivestedt, Goran
    St Eriks University Hospital, Sweden.
    Olofsson, Eva M.
    Umeå University, Sweden.
    Endophthalmitis after small-gauge vitrectomy: a retrospective case series from Sweden2016Ingår i: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 94, nr 8, s. 829-835Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PurposeTo investigate the anatomical and functional outcomes of acute-onset endophthalmitis after small-gauge vitrectomy. MethodsRetrospective case series of patients who underwent 23- or 25-gauge vitrectomy at four centres in Sweden between 2008 and 2012. Postvitrectomy endophthalmitis was identified through the search of the journal records of each institution, and the diagnosis was based on clinical criteria regardless of culture results. ResultsTwenty-four patients (24 eyes) were included. The incidence of endophthalmitis following small-gauge vitrectomy was 0.14%. Indications for small-gauge vitrectomy enclosed epiretinal membrane (n=13), retinal detachment (n=5) and others (n=6). Surgical technique included 23- and 25-gauge vitrectomy (23:1). Four eyes had sutured sclerotomies, and two had postoperative hypotony amp;lt;7mmHg. Days to endophthalmitis presentation varied between 1 and 21 (mean 66). Treatment methods included the following: tap and antibiotic injection (n=7), tap, antibiotic injection with subsequent vitrectomy (n=2) and prompt vitrectomy with antibiotics (n=15). Sixteen eyes (66.7%) were culture positive, whereas the other eight cases were culture negative. Anatomical results included evisceration (n=1), phthisis (n=1), and globe intact (n=22). Presenting best corrected visual acuity (BCVA) were hand motion (n=14), light perception (n=7), counting fingers (n=2), and no data (n=1). Functionally 19 eyes (79%) had Snellen VA 0.1; 11 eyes (46%) had VA 0.5 Mean logMar BCVA preoperatively and at the last follow-up were 2.07 +/- 0.6 and 0.79 +/- 0.99, respectively. ConclusionsIn spite of good anatomical and functional results, this study showed higher rate of endophthalmitis than the latest reports suggesting that small-gauge vitrectomy has reached the safety level of standard 20-gauge vitrectomy when infectious endophthalmitis is concerned.

  • 61.
    Piotr Czajka, Marcin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Frajdenberg, Agata
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Johansson, Björn
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM. Linköpings universitet, Medicinska fakulteten.
    Comparison of 1.8-mm incision versus 2.75-mm incision cataract surgery in combined phacoemulsification and 23-gauge vitrectomy2016Ingår i: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 94, nr 5, s. 507-513Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PurposeTo compare 1.8mm micro-incision and 2.75mm standard incision in coaxial cataract surgery combined with 23-Gauge (23G) vitrectomy with respect to intraoperative and postoperative complications and outcomes. MethodsIn this prospective study 30 eyes of 30 patients planned for combined phacoemulsification and 23G vitrectomy were enrolled, and randomized to undergo either Standard 2.75mm Incision Cataract Surgery (SICS, 15 eyes) or Coaxial 1.8mm Micro-Incision Cataract Surgery (C-MICS, 15 eyes) followed by vitrectomy. Inclusion criteria were cataract and macular disorders including macular hole, epiretinal membrane and vitreomacular traction. Data were collected at preoperative evaluation and 1 and 12months or more after surgery. ResultsIncision leakage occurred in two eyes (7%: one per group), retinal break in nine (30%: four in C-MICS, five in SICS). Fibrin in anterior chamber (AC) occurred day 1 in three eyes (10%: two C- and one SICS). Posterior capsule opacification developed in 22 eyes (78%: 13 MICS, nine SICS, p=0.1). A myopic shift of -0.630.7 was noted (-0.59 +/- 0.8 MICS, -0.68 +/- 0.6 SICS, p=0.74). Surgically induced astigmatism (SIA) was significantly smaller in C-MICS group (KP, -0.019 +/- 0.095 versus -0.141 +/- 0.219, p=0.0038) at 1month but not at final follow-up (KP, 0.0005 +/- 0.16 in C-MICS versus -0.057 +/- 0.12, p=0.3 ConclusionsBoth techniques were equally safe with respect to intraoperative and postoperative findings. Coaxial micro-incision cataract surgery (C-MICS) was associated with less surgically-induced astigmatism (SIA) 1month after surgery but differences were not statistically significant at final follow-up indicating a faster refractive recovery with C-MICS than with SICS.

  • 62.
    Piotr Czajka, Marcin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Fräjdenberg, Agata
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Stopa, Marcin
    Poznan Univ Med Sci, Poland.
    Pabin, Tomasz
    Poznan Univ Med Sci, Poland.
    Johansson, Björn
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Jakobsson, Gunnar
    Sahlgrens Univ Hosp, Sweden.
    Sutureless intrascleral fixation using different three-piece posterior chamber intraocular lenses: a literature review of surgical techniques in cases of insufficient capsular support and a retrospective multicentre study2019Ingår i: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    We present a literature review of surgical techniques of intraocular lens placement in eyes with insufficient capsular support, focusing on the most recent publications, together with a retrospective multicentre consecutive case series analysis of 103 eyes undergoing pars plana vitrectomy and sutureless intrascleral (SIS) fixation of a standard three-piece PCIOL. Many different approaches appear in the literature without any specific procedure achieving superior outcomes. Advantages and disadvantages vary between techniques. Common complications related to IOL fixation techniques were as follow: anterior chamber IOL: transient/permanent corneal oedema (9-66.6%), uveitis (1.1-39.3%); iris-fixated IOL: pupil ovalization (16-47.7%); and sutured scleral-fixated IOL: suture breakage/exposure (6.1-11%), vitreous haemorrhage: (5.5-16.6%). In our retrospective case series, indications for surgery were postoperative aphakia in 50 eyes (49%), IOL dislocation in 38 eyes (37%) and natural lens dislocation in 15 eyes (14%). Scleral tunnels for haptic fixation were created with (28 eyes, 27.2%) or without (75 eyes, 72.8%) 25 gauge trocar cannulas. Complications included transient hypotony (n = 20; 19.4%), corneal decompensation (n = 7; 6.7%), IOL dislocation (n = 6; 5.8%), cystoid macular oedema (n = 5; 4.8%), vitreous haemorrhage (n = 4; 3.8%) and retinal detachment (n = 4; 3.8%). Mean best corrected visual acuity improved from logMAR 0.65 to 0.36 at the final visit (p = 0.001). In conclusion, SIS fixation provides good anatomical and functional outcomes; however, complications can occur. The number of surgical approaches for IOL dislocation described in the literature indicates that optimal treatment remains to be found.

  • 63.
    Samarawickrama, Chameen
    et al.
    Moorfields Eye Hosp NHS Fdn Trust, England; UCL Inst Ophthalmol, England; Univ Sydney, Australia.
    Samanta, Ayan
    Uppsala Univ, Sweden; LV Prasad Eye Inst, India.
    Liszka, Aneta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Fagerholm, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Buznyk, Oleksiy
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. NAMS Ukraine, Ukraine.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. LV Prasad Eye Inst, India; Univ Montreal, Canada; Univ Montreal, Canada.
    Allan, Bruce
    Moorfields Eye Hosp NHS Fdn Trust, England; UCL Inst Ophthalmol, England.
    Collagen-Based Fillers as Alternatives to Cyanoacrylate Glue for the Sealing of Large Corneal Perforations2018Ingår i: Cornea, ISSN 0277-3740, E-ISSN 1536-4798, Vol. 37, nr 5, s. 609-616Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To describe the use of collagen-based alternatives to cyanoacrylate glue for the sealing of acute corneal perforations. Methods: A collagen analog comprising a collagen-like peptide conjugated to polyethylene glycol (CLP-PEG) and its chemical crosslinker were tested for biocompatibility. These CLP-PEG hydrogels, which are designed to act as a framework for corneal tissue regeneration, were then tested as potential fillers in ex vivo human corneas with surgically created full-thickness perforations. Bursting pressures were measured in each of 3 methods (n = 10 for each condition) of applying a seal: 1) cyanoacrylate glue with a polyethylene patch applied ab externo (gold standard); 2) a 100-mu m thick collagen hydrogel patch applied ab interno, and 3) the same collagen hydrogel patch applied ab interno supplemented with CLP-PEG hydrogel molded in situ to fill the remaining corneal stromal defect. Results: Cyanoacrylate gluing achieved a mean bursting pressure of 325.9 mm Hg, significantly higher than the ab interno patch alone (46.3 mm Hg) and the ab interno patch with the CLP-PEG filler (86.6 mm Hg). All experimental perforations were sealed effectively using 100 mu m hydrogel sheets as an ab interno patch, whereas conventional ab externo patching with cyanoacrylate glue failed to provide a seal in 30% (3/10) cases. Conclusions: An ab interno patch system using CLP-PEG hydrogels designed to promote corneal tissue regeneration may be a viable alternative to conventional cyanoacrylate glue patching for the treatment of corneal perforation. Further experimentation and material refinement is required in advance of clinical trials.

  • 64.
    Thangavelu, Muthukumar
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Adithan, Aravinthan
    Chonbuk Natl Univ, South Korea.
    Parvathaleswara, Sastry Thotapalli
    CSIR Cent Leather Res Inst, India.
    Munusamy, Chamundeeswari
    St Josephs Coll Engn, India.
    Morphological Modification of Carbon Nanoparticles after Interacting with Methotrexate as a Potential Anticancer Agent2018Ingår i: Pharmaceutical research, ISSN 0724-8741, E-ISSN 1573-904X, Vol. 35, nr 10, artikel-id UNSP 184Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose Production of highly penetrable and targetable drug delivery particles is mainly focused by current therapy and such focus is achieved in our present study. The carbon nanoparticle (CNP) prepared from purely natural source was modified from spherical shape to cylindrical floral like structure after treatment with the anticancer drug methotrexate (CM). Methods The physiochemical properties of the CNP and CM was characterized using FT-IR/Raman Spectrometer, XRD, SEM, AFM, particle size analyzer and its biological evaluation using haemolysis and MTT assay. Results The shift in FT-IR peaks at 1592, 1120 cm(-1) and peaks of raman spectra observed at 1303, 1300 cm(-1) represents ordered carbon nanotubes. The morphological change from spherical to cylindrical floral like structure was observed using SEM and AFM and its particle size distribution analysis shows an average diameter of 269 nm for CM. XRD peak at 2 theta = 23.86A degrees (002) indicates the presence of large amount of amorphous material that corresponds to multi-walled carbon nanotubes. Haemocompatibility studies proved the safety level usage as 100 mu g/ml and MTT assay shows viability rate of 85-98% with mouse embryonic fibroblast (NIH/3 T3) and 30-45% with pancreatic carcinoma (MIA PaCa-2) and gastric cancer cell lines (SNU- 484) respectively.These results are also supported by phase contrast microscope images observed after staining with calcein AM and EthD-1. Conclusions The morphologically modified CNPs has shown good anticancer, biocompatibility and haemocompatibility property which is an important criterion to be satisfied by a biomedical product.

  • 65.
    Xeroudaki, Maria
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Peebo, Beatrice
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Germundsson, Johan
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap.
    Fagerholm, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Lagali, Neil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    RGTA in corneal wound healing after transepithelial laser ablation in a rabbit model: a randomized, blinded, placebo-controlled study2016Ingår i: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 94, nr 7, s. 685-691Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PurposeTo evaluate the efficacy of the agent RGTA for epithelial, stromal and nerve regeneration after laser-induced corneal wounding in rabbits. MethodsAfter excimer laser wounding of the anterior cornea in 25 New Zealand white rabbits, topical RGTA or placebo was applied in a randomized, masked manner. Fluorescein epithelial staining was performed on the first 5 postoperative days. In vivo confocal microscopy of corneal subbasal nerves and stroma was performed preoperatively and on week 2, 4, 8 and 16. At 16weeks, corneas were stained for beta-III tubulin expression. ResultsPostoperatively, all epithelia had closed by at least 90% after the third postoperative day. No significant difference in epithelial wound size was found between RGTA and placebo-treated groups, and RGTA did not hinder fluorescein binding. After epithelial wound closure, corneas remained transparent to 16weeks. By confocal microscopy, subclinical stromal haze was significantly deeper in placebo-treated eyes (mean depth 60m) relative to RGTA group (52m), p=0.02. Regenerating beta-III tubulin-positive subbasal nerves were observed in all corneas, but partial masking by haze rendered quantitative analysis unreliable. ConclusionsRGTA restored stromal microarchitecture and reduced subclinical haze relative to placebo. The mild epithelial wound quickly healed regardless of treatment suggesting an optimal natural healing process in freshly wounded healthy corneas, and indicating that RGTA may be more suitable for healing of chronic or more aggressive wounds. Limitations of the rabbit model for nerve quantification in the presence of haze should also be recognized.

  • 66.
    Xiao, Jiaxin
    et al.
    Univ Oslo, Norway; Oslo Univ Hosp, Norway.
    Adil, Mohammed Yasin
    Univ Oslo, Norway; Oslo Univ Hosp, Norway.
    Chen, Xiangjun
    Norwegian Dry Eye Clin, Norway; Sorlandet Hosp, Norway; Oslo Univ Hosp, Norway; Univ Oslo, Norway; Univ Coll Southeast Norway, Norway.
    Utheim, Oygunn A.
    Norwegian Dry Eye Clin, Norway.
    Raeder, Sten
    Norwegian Dry Eye Clin, Norway.
    Tonseth, Kim Alexander
    Oslo Univ Hosp, Norway; Oslo Univ Hosp, Norway.
    Lagali, Neil
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för logopedi, otorhinolaryngologi och audiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM. Sorlandet Hosp, Norway.
    Dartt, Darlene A.
    Harvard Med Sch, MA 02115 USA.
    Utheim, Tor P.
    Oslo Univ Hosp, Norway; Sorlandet Hosp, Norway; Oslo Univ Hosp, Norway; Univ Oslo, Norway; Univ Coll Southeast Norway, Norway; Oslo Univ Hosp, Norway; Stavanger Univ Hosp, Norway.
    Functional and Morphological Evaluation of Meibomian Glands in the Assessment of Meibomian Gland Dysfunction Subtype and Severity2020Ingår i: American Journal of Ophthalmology, ISSN 0002-9394, E-ISSN 1879-1891, Vol. 209, s. 160-167Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: To classify subtypes of meibomian gland dysfunction (MGD) and evaluate the dependency of dry eye signs, symptoms, and parameters on MGD subtype. DESIGN: Cross-sectional study. Study Population: the right eyes of 447 patients with MGD of various subtypes and 20 healthy volunteers. METHODS: Patients were divided into 4 subtypes of MGD based on meibum expression, meibum quality, and MG loss on meibography images (meibograde of 0-6). Subtypes were patients with high meibum delivery (hypersecretory and nonobvious MGD) and those with low meibum delivery (hyposecretory and obstructive MGD). Additional clinical tests included tear film break-up time (TFBUT), ocular staining, osmolarity, Schirmer I, blink interval timing and the Ocular Surface Disease Index (OSDI) questionnaire. RESULTS: A total of 78 eyes had hypersecretory MGD; 49 eyes had nonobvious MGD; 66 eyes had hyposecretory MGD; and 254 eyes had obstructive MGD. Increased tear film osmolarity and lower TFBUT were found in the low-delivery groups; hyposecretory (P = 0.006, P = 0.016) and obstructive MGD (P = 0.008, P = 0.006) relative to high-delivery MGD (hypersecretory and nonobvious groups, respectively). Worse ocular symptoms and ocular staining were also found in low-delivery MGD groups than the high delivery MGD groups (P amp;lt; 0.01 and P amp;lt; 0.006, respectively). " CONCLUSIONS: Patients with low-delivery MGD had worse dry eye parameters and ocular symptoms than those with high meibum delivery, indicating the pivotal role of meibum secretion in ocular surface health that should be targeted in MGD therapy. Furthermore, nonobvious MGD cannot be diagnosed using conventional dry eye tests and requires morphologic assessment of meibography images to confirm MG loss. ((C) 2019 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

  • 67.
    Xiao, Jiaxin
    et al.
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Adil, Muhammed Yasin
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Olafsson, Jonatan
    Oslo Univ Hosp, Norway; Norwegian Dry Eye Clin, Norway.
    Chen, Xiangjun
    Norwegian Dry Eye Clin, Norway; Sorlandet Hosp, Norway; Oslo Univ Hosp, Norway; Univ Oslo, Norway; Univ South Eastern Norway, Norway.
    Utheim, Oygunn A.
    Norwegian Dry Eye Clin, Norway.
    Raeder, Sten
    Norwegian Dry Eye Clin, Norway.
    Lagali, Neil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM. Sorlandet Hosp, Norway.
    Dartt, Darlene A.
    Harvard Med Sch, MA 02115 USA.
    Utheim, Tor P.
    Univ Oslo, Norway; Sorlandet Hosp, Norway; Oslo Univ Hosp, Norway; Oslo Univ Hosp, Norway; Univ Oslo, Norway; Univ South Eastern Norway, Norway; Stavanger Univ Hosp, Norway.
    Diagnostic Test Efficacy of Meibomian Gland Morphology and Function2019Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikel-id 17345Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Meibomian gland dysfunction (MGD) is the leading cause of dry eye and proposed treatments are based on disease severity. Our purpose was to establish reliable morphologic measurements of meibomian glands for evaluating MGD severity. This retrospective, cross-sectional study included 100 MGD patients and 20 controls. The patients were classified into dry eye severity level (DESL) 1-4 based on symptoms and clinical parameters including tear-film breakup time, ocular staining and Schirmer I. The gland loss, length, thickness, density and distortion were analyzed. We compared the morphology between patients and controls; examined their correlations to meibum expressibility, quality, and DESL. Relative to controls, the gland thickness, density and distortion were elevated in patients (p amp;lt; 0.001 for all tests). The area under the receiver operating characteristic curve was 0.98 (95% confidence interval [CI], 0.96-1.0) for gland loss, and 0.96 (CI 0.91-1.0) for gland distortion, with a cutoff value of six distorted glands yielding a sensitivity of 93% and specificity of 97% for MGD diagnosis. The gland distortion was negatively correlated to the meibum expressibility (r = -0.53; p amp;lt; 0.001) and DESL (r = -0.22, p = 0.018). In conclusion, evaluation of meibomian gland loss and distortion are valuable complementary clinical parameters to assess MGD status.

  • 68.
    Yazdani, Mazyar
    et al.
    Oslo Univ Hosp, Norway; Norwegian Dry Eye Clin, Norway.
    Chen, Xiangjun
    Norwegian Dry Eye Clin, Norway; Arendal Hosp, Norway; Univ Oslo, Norway; Univ Coll Southeast Norway, Norway.
    Tashbayev, Behzod
    Norwegian Dry Eye Clin, Norway; Univ Oslo, Norway.
    Utheim, Oygunn A.
    Oslo Univ Hosp, Norway; Norwegian Dry Eye Clin, Norway.
    Raeder, Sten
    Norwegian Dry Eye Clin, Norway.
    Lagali, Neil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Stojanovic, Aleksandar
    Univ Hosp North Norway, Norway.
    Dartt, Darlene A.
    Harvard Med Sch, MA USA.
    Utheim, Tor P.
    Oslo Univ Hosp, Norway; Norwegian Dry Eye Clin, Norway; Arendal Hosp, Norway; Univ Oslo, Norway; Univ Coll Southeast Norway, Norway; Oslo Univ Hosp, Norway; Oslo Univ Hosp, Norway; Stavanger Univ Hosp, Norway; Univ Bergen, Norway.
    Tear Production Levels and Dry Eye Disease Severity in a Large Norwegian Cohort2018Ingår i: Current Eye Research, ISSN 0271-3683, E-ISSN 1460-2202, Vol. 43, nr 12, s. 1465-1470Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To determine if the Schirmer I test (without anesthesia) cut-off value is a predictor of dry eye severity in a large Norwegian cohort of dry eye disease (DED) patients, which are grouped into six levels of tear production. Methods: Patients (n = 1090) with DED of different etiologies received an extensive dry eye work-up: osmolarity (Osm), tear meniscus height (TMH), tear film break-up time (TFBUT), ocular protection index (OPI), ocular surface staining (OSS), Schirmer I test (ST), meibum expressibility (ME), and meibum quality (MQ). Classification of dry eye severity level (DESL) and diagnosis of meibomian gland dysfunction (MGD) were also included. The cohort was divided into six groups: below and above cut-off values of 5 (groups 1 and 2), 10 (groups 3 and 4), and 15 mm (groups 5 and 6) of ST. Mann-Whitney test and Chi-Square test were used for group comparison of parameters (p amp;lt;= 0.05). Results: The groups 1, 3, and 5 had values indicating more severe DED than the groups 2, 4, 6 with significant difference in DESL, Osm, TFBUT, OPI, OSS, and TMH. Regardless of the choice of cut-off values, there was no statistically significant difference in ME, MQ, and MGD between groups below and above selected cut-off value. When gender difference was considered in each group, significant difference was only observed for DESL (groups 2, 4, and 5), TFBUT (groups 2, 4, and 5), OPI (groups 2 and 6), and ME (group1). Conclusions: Schirmer I is a robust discriminator for DESL, Osm, TFBUT, OPI, OSS, and TMH, but not for ME, MQ, and MGD. Patients with lower tear production levels presented with more severe DED at all three defined cut-off values. Interestingly, the differences in the mean values of DESL were minimal although statistically significant. Thus, the clinical value of different Schirmer levels appears to be limited.

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