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  • 151.
    Kobelt, Gisela
    et al.
    European Health Economics, Spéracèdes, France.
    Jonsson, Björn
    Bergström, Anders
    Chen, Enping
    Karolinska institutet, S:t Eriks ögonsjukhus.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Alm, Albert
    Uppsala universitet, medicinska fakulteten.
    Cost-effectiveness analysis in glaucoma: what drives utility? Results from a pilot study in Sweden.2006In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 84, no 3, p. 363-71Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate the effect of different levels of visual field defect in glaucoma on utilities and to test if utilities could be assessed using a general questionnaire such as the EQ-5D. METHODS: A cross-sectional study in 199 patients with ocular hypertension or open-angle glaucoma grouped into 5 severity stages according to visual field defects was performed in 4 specialized ophthalmic centres. Descriptive analysis was performed for the sample and by stage, and the effect of vision loss on utility was investigated with multiple step-wise regression analysis. RESULTS: The mean age of the sample was 70 and the mean MD in the worse eye was -13.1 dB (SD 10.2). Visual acuity (VA) was 0.63 and 0.87 in the worse and better eye, respectively, and the mean utility was 0.80 (SD 0.23). Utility decreased with increasing glaucomatous damage, ranging from 0.84 for mild disease to 0.72 for severe damage (MD -2.5 to -28.1), but the difference between the groups was not statistically significant when controlling for co-morbidity, except for the most severe stage (p < 0.01). In multiple regression analysis, visual field in the better eye was significantly correlated with utility, and there was an indirect correlation between visual field in the worse eye and utility: the effect of total VA on utility was significant, and MD in the worse eye was correlated with total VA. CONCLUSIONS: Utility is strongly correlated with overall vision. Our results suggest a relationship between glaucomatous damage and utility, and patients with severe damage have a significantly lower utility. However, this should be further investigated in larger samples that include more patients with moderate-severe bilateral damage.

  • 152.
    Krachler, Benno
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Jerdén, Lars
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Kunskap om levnadsvanor värderas olika på läkarutbildningarna: en genomgång av 124 skriftliga examinationer2018In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115, article id EWPDArticle in journal (Refereed)
    Abstract [en]

    Lifestyle factors are crucial for prevention and management of many non-communicable diseases such as hypertension, stroke, diabetes, coronary heart disease and chronic obstructive pulmonary disease. Lifestyle medicine is included in national learning outcomes for undergraduate medical education in Sweden. Since assessment drives learning, we reviewed questions from 124 written examinations from all 7 medical schools in Sweden, conducted between 2012 and 2015. There is up to a 5-fold difference between different universities in the weight attached to lifestyle-related knowledge compared to knowledge related to pharmacological treatments.

  • 153.
    Krachler, Benno
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Jerdén, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Written examinations in Swedish medical schools: minds molded to medicate?2017In: American Journal of Lifestyle Medicine, ISSN 1559-8276, E-ISSN 1559-8284Article in journal (Refereed)
    Abstract [en]

    Lifestyle medicine (LM) is part of official educational goals in Swedish medical schools. We studied questions concerning 5 noncommunicable diseases: diabetes, hypertension, coronary heart disease (CHD), chronic obstructive pulmonary disease (COPD), and stroke from 124 written examinations conducted between 2012 and 2015. LM knowledge yielded between 2% and 10%, whereas pharmacology-related knowledge yielded between 24% and 50%, of total points. The multiples at which pharmacology-related knowledge was valued higher than LM knowledge were 2.4 for COPD (P < .056), 4.3 for diabetes (P < .0001), 4.8 for hypertension (P < .0001), 5.2 for CHD (P < .0001), and 31.5 for stroke (P < .0001). Our results indicate that lifestyle-related knowledge, though covered by official teaching goals, is currently underrated in Swedish medical education.

  • 154.
    Kristiansen, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Blood flow rate of ophthalmic artery in patients with normal tension glaucoma and healthy controls2018In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 9Article in journal (Other academic)
    Abstract [en]

    Purpose: To determine the blood flow rate of the ophthalmic artery (OA) in patients with Normal Tension Glaucoma (NTG) compared to age-matched healthy controls using phase-contrast magnetic resonance imaging (PCMRI).

    Methods: Seventeen patients with treated NTG (11 female; mean age: 70±9 years) and 16 age-matched healthy controls (10 female; mean age: 71±9 years) underwent PCMRI using a 3-Tesla scanner as well as ophthalmological examinations including visual acuity, Goldmann Applanation Tonometry, Humphrey perimetry and fundoscopy. Ophthalmic blood flow was acquired using a 2D PCMRI sequence set to a spatial resolution of 0.35mm/pixel. Mean flow rate and cross-sectional area was calculated using Segment Software. The eye with the most severe glaucomatous damage classified by visual field index (VFI) was chosen for comparison. The primary outcome was blood flow rate of OA.

    Results: The mean VFI was 41% ± 26 (mean±SD) for the worse NTG eyes. The intraocular pressure was 13.6±2.6 mmHg for NTG eyes and 13.8±2.1 mmHg for control eyes. The blood flow rate in the NTG group was 9.6±3.7 ml/min compared to 11.8±5.5 ml/min in the control group. The area was 1.7±0.3 mm2 and 2.0±0.6 mm2 respectively. No statistical significance was found between NTG and the control group regarding blood flow rate (p=0.07) or OA area (p=0.12).

    Conclusions: Despite OA being an anastomosis between the intracranial and extracranial circulation, possibly generating an eye unrelated variability in blood flow, we found a trend level reduction of approximately 2 ml/min in NTG. The finding warrants blood flow rate analysis of smaller arteries specifically supplying the eye, e.g. the central retinal artery.

  • 155.
    Köhn, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bowne, Sara J
    The University of Texas Health Science Center, Laboratory for Molecular Diagnosis of Inherited Eye Diseases, Human Genetics Center .
    Daiger, Stephen P
    The University of Texas Health Science Center, Laboratory for Molecular Diagnosis of Inherited Eye Diseases, Human Genetics Center .
    Burstedt, Marie SI
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Kadzhaev, Konstantin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Breakpoint characterization of a novel ~59 kb genomic deletion on 19q13.42 in autosomal dominant retinitis pigmentosa with reduced penetrance2009In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 17, no 5, p. 651-655Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to identify and characterize the underlying molecular mechanisms in autosomal-dominant retinitis pigmentosa (adRP) with incomplete penetrance in two Swedish families. An extended genealogical study and haplotype analysis indicated a common origin. Mutation identification was carried out by multiplex ligation-dependent probe amplification (MLPA) and sequencing. Clinical examinations of adRP families including electroretinography revealed obligate gene carriers without abnormalities, which indicated incomplete penetrance. Linkage analysis resulted in mapping of the disease locus to 19q13.42 (RP11). Sequence analyses did not reveal any mutations segregating with the disease in eight genes including PRPF31. Subsequent MLPA detected a large genomic deletion of 11 exons in the PRPF31 gene and, additionally, three genes upstream of the PRPF31. Breakpoints occurred in intron 11 of PRPF31 and in LOC441864, 'similar to osteoclast-associated receptor isoform 5.' An almost 59 kb deletion segregated with the disease in all affected individuals and was present in several asymptomatic family members but not in 20 simplex RP cases or 94 healthy controls tested by allele-specific PCR. A large genomic deletion resulting in almost entire loss of PRPF31 and three additional genes identified as the cause of adRP in two Swedish families provide an additional evidence that mechanism of the disease evolvement is haploinsufficiency. Identification of the deletion breakpoints allowed development of a simple tool for molecular testing of this genetic subtype of adRP.

  • 156.
    Köhn, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Bowne, Sara J
    Laboratory for Molecular Diagnosis of Inherited Eye Diseases, Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
    S Sullivan, Lori
    Laboratory for Molecular Diagnosis of Inherited Eye Diseases, Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
    Daiger, Stephen P
    Laboratory for Molecular Diagnosis of Inherited Eye Diseases, Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
    Burstedt, Marie S I
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Kadzhaev, Konstantin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Breakpoint characterization of a novel approximately 59 kb genomic deletion on 19q13.42 in autosomal-dominant retinitis pigmentosa with incomplete penetrance.2009In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 17, no 5, p. 651-655Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to identify and characterize the underlying molecular mechanisms in autosomal-dominant retinitis pigmentosa (adRP) with incomplete penetrance in two Swedish families. An extended genealogical study and haplotype analysis indicated a common origin. Mutation identification was carried out by multiplex ligation-dependent probe amplification (MLPA) and sequencing. Clinical examinations of adRP families including electroretinography revealed obligate gene carriers without abnormalities, which indicated incomplete penetrance. Linkage analysis resulted in mapping of the disease locus to 19q13.42 (RP11). Sequence analyses did not reveal any mutations segregating with the disease in eight genes including PRPF31. Subsequent MLPA detected a large genomic deletion of 11 exons in the PRPF31 gene and, additionally, three genes upstream of the PRPF31. Breakpoints occurred in intron 11 of PRPF31 and in LOC441864, 'similar to osteoclast-associated receptor isoform 5.' An almost 59 kb deletion segregated with the disease in all affected individuals and was present in several asymptomatic family members but not in 20 simplex RP cases or 94 healthy controls tested by allele-specific PCR. A large genomic deletion resulting in almost entire loss of PRPF31 and three additional genes identified as the cause of adRP in two Swedish families provide an additional evidence that mechanism of the disease evolvement is haploinsufficiency. Identification of the deletion breakpoints allowed development of a simple tool for molecular testing of this genetic subtype of adRP.

  • 157.
    Köhn, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Burstedt, Marie SI
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Jonsson, Frida
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Kadzhaev, Konstantin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Haamer, Eneli
    Asper Biotech, Tartu, Estonia.
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Carrier of R14W in carbonic anhydrase IV presents Bothnia dystrophy phenotype caused by two allelic mutations in RLBP12008In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 49, no 7, p. 3172-3177Article in journal (Refereed)
    Abstract [en]

    Purpose: Bothnia dystrophy (BD) is an autosomal recessive retinitis pigmentosa (arRP) associated with the c.700C>T mutation in the RLBP1 gene. Testing of patients with BD has revealed the c.700C>T mutation on one or both alleles. The purpose of this study was to elucidate the underlying genetic mechanisms along with a clinical evaluation of the heterozygous patients with BD.

    Methods: Patients with BD heterozygous for the RLBP1 c.700C>T were tested for 848 mutations by arrayed primer-extension technology. Further mutation detection was performed by PCR-restriction fragment length polymorphism (RFLP), sequencing, denaturing (d)HLPC and allelic discrimination. The ophthalmic examinations were performed in all c.700C>T heterozygotes.

    Results: The clinical findings in 10 BD heterozygotes were similar to those in the homozygotes. The presence of a second mutation, c.677T>A, corresponding to p.M226K was detected in all 10 cases. Segregation analysis showed that the mutations were allelic, and the patients were compound heterozygotes [c.677T>A]+[c.700C>T]. One of those patients was also a carrier of the c.40C>T corresponding to the p.R14W change in carbonic anhydrase IV (CAIV) associated with autosomal dominant RP, RP17. His mother, a carrier of the identical change was declared healthy after ophthalmic examination. This sequence variant was found in 6 of 143 tested blood donors.

    Conclusions: The high frequency of arRP in northern Sweden is due to two mutations in the RLBP1 gene: c.677T>A and c.700C>T. BD is caused by the loss of CRALBP function due to changed physical features and impaired activity of retinoid binding. The CAIV p.R14W sequence variant found in one of the patients with a BD phenotype is a benign polymorphism in a population of northern Sweden.

  • 158.
    Köhn, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Kadzhaev, Konstantin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Burstedt, Marie S I
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Haraldsson, Susann
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Mutation in the PYK2-binding domain of PITPNM3 causes autosomal dominant cone dystrophy (CORD5) in two Swedish families.2008In: Recent Advances in Retinal Degeneration / [ed] Robert E. Anderson, Matthew M. LaVail, Joe G. Hollyfield, Springer , 2008, Vol. 613, p. 229-234Conference paper (Refereed)
    Abstract [en]

     

     

  • 159.
    Köhn, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Kadzhaev, Konstantin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Burstedt, Marie SI
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Haraldsson, Susann
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Hallberg, Bengt
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Mutation in the PYK2-binding domain of PITPNM3 causes autosomal dominant cone dystrophy (CORD5) in two Swedish families2007In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 15, no 6, p. 664-671Article in journal (Refereed)
    Abstract [en]

    Autosomal dominant cone dystrophy (CORD5) (MIM 600977) is a rare disease predominantly affecting cone photoreceptors. Here we refine the CORD5 locus previously mapped to 17p13 from 27 to 14.3 cM and identified a missense mutation, Q626H in the phosphatidylinositol transfer (PIT) membrane-associated protein (PITPNM3) (MIM 608921) in two Swedish families. PITPNM3, known as a human homologue of the Drosophila retinal degeneration B (rdgB), lacks the N-terminal PIT domain needed for transport of phospholipids, renewal of photoreceptors membrane and providing the electroretinogram (ERG) response to light. In our study, the mutation causing CORD5 is located in the C-terminal region interacting with a member of nonreceptor protein tyrosine kinases, PYK2. Our finding on the first mutation in the human homologue of Drosophila rdgB indicates novel pathways and a potential important role of the PITPNM3 in mammalian phototransduction.

  • 160.
    Köhn, Linda
    et al.
    Umeå University, Faculty of Medicine, Medical Biosciences, Medical and Clinical Genetics.
    Kohl, Susanne
    Molecular genetics Laboratory, Institute of Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Germany.
    Bowne, Sara J
    Human Genetics Center and Dept. of Ophthalmology and Visual Science, University of Texas Health Science Center, USA.
    Sullivan, Lori S
    Human Genetics Center and Dept. of Ophthalmology and Visual Science, University of Texas Health Science Center, USA.
    Kellner, Ulrich
    AugenZentrum Siegburg, Germany.
    Daiger, Stephen P
    Human Genetics Center and Dept. of Ophthalmology and Visual Science, University of Texas Health Science Center, USA.
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Clinical Sciences, Ophthalmology.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Medical Biosciences, Medical and Clinical Genetics.
    Low mutation rate in PITPNM3 in cone/cone-rod dystrophiesManuscript (preprint) (Other academic)
  • 161.
    Köhn, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Kohl, Susanne
    Bowne, Sara J
    Sullivan, Lori S
    Kellner, Ulrich
    Daiger, Stephen P
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    PITPNM3 is an uncommon cause of cone and cone-rod dystrophies.2010In: Ophthalmic Genetics, ISSN 1381-6810, E-ISSN 1744-5094, Vol. 31, no 3, p. 139-140Article in journal (Refereed)
    Abstract [en]

    The first mutation in PITPNM3, a human homologue of the Drosophila retinal degeneration (rdgB not not) gene was reported in two large Swedish families with autosomal dominant cone dystrophy. To establish the global impact that PITPNM3 has on retinal degenerations we screened 163 patients from Denmark, Germany, the UK, and USA. Four sequence variants, two missence mutations and two intronic changes were identified in the screen. Thus, mutations in PITPNM3 do not appear to be a major cause of cone or cone-rod dystrophy.

  • 162.
    Larsson, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Gouveia-Figueira, Sandra
    Umeå University.
    Claesson, Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Lehtipalo, Stefan
    Umeå University.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Tyden, Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Pinto, Rui
    Umeå University.
    Nording, M. L.
    Umeå University.
    Oxylipin Profiling In The Acute Respiratory Distress Syndrome2016In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 193, article id A4419Article in journal (Refereed)
  • 163.
    Law, Lucy
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Beckman Rehnman, Jeannette
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Deminger, A.
    Klingberg, E.
    Jacobsson, L. T. H.
    Forsblad-d'Elia, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology. Univ Gothenburg, Gothenburg, Sweden.
    FACTORS RELATED TO HEALTH RELATED QUALITY OF LIFE IN ANKYLOSING SPONDYLITIS, OVERALL AND STRATIFIED BY SEX2018In: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 36, no 4, p. 714-714, article id P36Article in journal (Other academic)
  • 164.
    Law, Lucy
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Beckman Rehnman, Jeannette
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Deminger, Anna
    Klingberg, Eva
    Jacobsson, Lennart T. H.
    Forsblad-d'Elia, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology. Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Factors related to health-related quality of life in ankylosing spondylitis, overall and stratified by sex2018In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 20, article id 284Article in journal (Refereed)
    Abstract [en]

    Background: Ankylosing spondylitis (AS) begins early in life and often leads to reduced physical function, but less is known about the impacts it has on health-related quality of life (HRQoL). The aims of this study were to assess HRQoL using the Short Form-36 (SF-36) in a cohort of patients with AS compared with controls and to examine associations between SF-36 scores and spinal radiographic changes, physical function, disease activity and demographic data overall and stratified by sex.

    Methods: A cohort of patients with AS from Western Sweden were assessed using the Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with spinal radiographs, clinical examination and questionnaires, including the Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Patient Global (BASG) and SF-36. Each patient's SF-36 results were compared with those of five age-matched and sex-matched persons (n=1055) from the SF-36 Swedish normative population database. Associations between SF-36 physical component summary (PCS) and mental component summary (MCS) scores and disease-related and demographic factors were investigated using univariate and multivariable ogistic regression analyses with PCS and MCS below/above their respective median values as dependent variables.

    Results: A total of 210 patients, age (median, IQR) 49.0 (21.2) years, symptom duration 24.0 (21.0) years, men 57.6% and HLAB27 87.1% were included. Patients with AS scored significantly lower (p<0.001) compared to controls in all SF-36 domains and component summaries; PCS 42.4 (14.5) in AS versus 52.4 (11.8) in controls and MCS 47.9 (20.0) in AS versus 54.1 (10.1) in controls. Both men and women scored significantly lower in PCS compared with MCS. Multivariable logistic regression analyses revealed that living without a partner (OR 2.38, 95% CI 1.00-5.67), long symptom duration (year in decade OR 1.66, 95% CI 1.16-2.37), higher BASFI (OR 1.98, 95% CI 1.46-2.70) and ASDAS 2.1 (OR 3.32, 95% CI 1.45-7.62) were associated with worse PCS, while living without a partner (OR 3.04, 95% CI 1.34-6.91), fatigue (visual analogue scale for global fatigue greater than the median (OR 6.36, 95% CI 3.06-13.19) and ASDAS 2.1 (OR 2.97, 95% CI 1.41-6.25) with worse MCS. Some differences between sexes were observed in the results.

    Conclusions: The patients with AS had significantly lower HRQoL compared with controls. PCS was more affected compared to MCS in both sexes. Both disease-related and demographic factors were associated with HRQoL, partly overlapping for PCS and MCS. Factors associated with HRQoL showed some differences between sexes. By modifying factors, such as ASDAS-CRP and fatigue, HRQoL may potentially be improved.

    Trial registration: ClinicalTrials.gov, NCT00858819. Registered on 9 March 2009. Last updated on 28 May 2015.

  • 165.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Aspects on prostanoid and cholinergic effects on aqueous humour dynamics in human eyes1999In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 77, no 6, p. 725-726Article in journal (Refereed)
  • 166.
    Linden, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Heijl, Anders
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Aspberg, Johan
    Andersson Geimer, Sabina
    Bengtsson, Boel
    Initial intraocular pressure reduction by mono‐ versus multi‐therapy in patients with open‐angle glaucoma: results from the Glaucoma Intensive Treatment Study2018In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 96, no 6, p. 567-572Article in journal (Refereed)
    Abstract [en]

    Purpose: To study newly diagnosed glaucoma patients given mono‐ or multi‐therapy regarding differences in initial intraocular pressure (IOP) reduction, target IOP levels reached and influence of untreated baseline IOP on IOP reduction.

    Methods: Patients newly diagnosed with manifest primary open‐angle glaucoma and included in the Glaucoma Intensive Treatment Study (GITS) were randomized to immediate intensive treatment with any of three different IOP‐lowering substances supplied in two bottles plus 360° laser trabeculoplasty or to conventional stepwise treatment starting with a single‐drug. Intraocular pressure reduction was analysed 1 month after initiation of treatment.

    Results: One hundred eighteen patients (143 eyes) received mono‐therapy and 122 patients (152 eyes) multi‐therapy. Median baseline IOP was 24.0 (min: 9.7, max: 56.0) mmHg in mono‐therapy eyes and 24.0 (min: 12.3, max: 48.5) mmHg in multi‐therapy eyes (p = 0.56). After 1 month in the two groups, respectively, values for median IOP reduction were 6.3 (range: −5.3–31.0) and 11.0 (range: 0.7–34.5) mmHg, and for mean relative decline 26.8 (range: −32.0–55.4) and 46.0 (range: 4.6–81.6) % (p = 0.000). A larger proportion of the multi‐therapy patients reached each target IOP level (p = 0.000). The higher the baseline IOP, the larger the observed pressure reduction, considering both absolute and relative figures. The effect was more pronounced in eyes with multi‐therapy than in those with mono‐therapy (p = 0.000). For every mmHg higher IOP at baseline, the IOP was reduced by an additional 0.56 (mono‐therapy) or 0.84 (multi‐therapy) mmHg.

    Conclusion: Intensive treatment led to considerably greater IOP reduction than mono‐therapy. Among patients with IOP ≥30 mmHg at diagnosis an IOP of <16 was reached in 2/3 of those with multi‐therapy but in none with mono‐therapy. The IOP reduction was highly dependent on the untreated IOP level.

  • 167.
    Lindström, Mona
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Satellite cell heterogeneity with respect to expression of MyoD, myogenin, Dlk1 and c-Met in human skeletal muscle: application to a cohort of power lifters and sedentary men2010In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 134, no 4, p. 371-385Article in journal (Refereed)
    Abstract [en]

    Human satellite cells (SCs) are heterogeneous with respect to markers for their identification in the niche between the muscle fibre plasma membrane and its basal lamina. We have previously shown that, in biopsies from highly competitive power lifters, power lifters with long-term use of anabolic steroids and a population of healthy sedentary men, antibodies against the neuronal cell adhesion molecule (NCAM) and the paired box transcription factor Pax7 together label 94% of the SCs, NCAM alone labels 4% and Pax7 alone labels 1%. In the present study, we have further studied these biopsies with four markers related to SC activation and differentiation. Our study unequivocally shows that staining for MyoD and myogenin are present in nuclei of SCs and of myoblasts and myotubes in areas of muscle fibre regeneration. Staining for c-Met was observed in a proportion of Pax7+ SCs. However, widespread labelling of the sarcolemma precluded the quantification of c-Met+/Pax7+ SCs and the use of c-Met as a reliable SC marker. Pax7+ SCs labelled by anti-Delta like1 (Dlk1) were present in all samples but in variable proportions, whereas muscle progenitor cells related to repair were Dlk1⁻. Staining for Dlk1 was also observed in Pax7⁻ interstitial cells and in the cytoplasm of some small muscle fibres. Interestingly, the proportion of Dlk1+/Pax7+ SCs was significantly different between the groups of power lifters. Thus, our study confirms that human SCs show marked heterogeneity and this is discussed in terms of SC activation, myonuclei turnover, muscle fibre growth and muscle fibre damage and repair.

  • 168.
    Lindström, Mona
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Tjust, Anton E.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Domellöf, Fatima Pedrosa
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Pax7-Positive Cells/Satellite Cells in Human Extraocular Muscles2015In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 56, no 10, p. 6132-6143Article in journal (Refereed)
    Abstract [en]

    PURPOSE. We quantified and investigated the distribution of Pax7-positive cells/satellite cells (SCs) in the human extraocular muscles (EOMs). METHODS. An immunofluorescence multiple-marker method simultaneously combining two SC markers (Pax7, NCAM), detection of the basement membrane (laminin) and cell nuclei (4',6-diamidino-2-phenylindole [DAPI]), was used on the anterior, middle, and posterior portions of EOMs from five healthy donors. Pax7-positive cell and SC content, myonuclear content, myofiber cross-sectional area, and myonuclear domain were analyzed in single cross-sections. Between 3915 and 13,536 myofibers per muscle cross-section and myofibers from the entire EOM cross-section were analyzed for quantification of Pax7-positive cells per myofiber (Pax7/F).

    RESULTS. The number of Pax7/F in the human EOMs varies along the length of the muscle with twice as high Pax7/F in the anterior part of the EOMs, but within the range of what has been previously reported for normal adult limb muscles. Furthermore, there are Pax7-positive cells in positions other than the classical SC position and the myonuclear domain size of adult EOMs is noticeably smaller than that previously reported for other adult skeletal muscles.

    CONCLUSIONS. Previous data on differences in Pax7-positive cell/SC abundance between EOMs and limb muscles must be reconsidered and the characteristics of different Pax7-positive cell populations further investigated. Higher numbers of Pax7-positive cells in the anterior portion of the EOMs may have a bearing for strabismus surgery involving sectioning of the muscle fibers.

  • 169.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Aspects on prostanoid and cholinergic effects on aqueous humour dynamics in human eyes1997Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The discovery of the ocular hypotensive effect of topically applied prostaglandins (PGs) has raised a number of questions about the mechanisms of action involved. The aim of the present thesis was to answer some of these questions.

    PGs reduce the intraocular pressure (IOP) by increasing uveoscleral flow through the ciliary muscle, but the exact mechanism is not known. Morphological changes may be involved. PGs are also involved in the inflammatory response. In the first study the aim was to investigate the effect of latanoprost, a prostaglandin F2 a-analogue, on the blood-aqueous barrier and the IOP restoration after long-term treatment. 26 glaucoma patients were treated with latanoprost (50 pg/ml) once daily for 6-12 months. Aqueous protein concentration was followed with a laser flare meter in 16 patients throughout this period. No change was observed. IOP increased slowly after withdrawal of treatment. It was concluded that latanoprost has no clinically significant effect on the permeability of the blood-aqueous barrier and that the IOP will return to pretreatment levels within a few weeks, indicating that any changes in the ciliary muscle morphology are reversible.

    In 20 healthy volunteers it was attempted to prevent the ocular hypotensive effect of latanoprost by inhibiting uveoscleral flow by a pronounced ciliary muscle contraction. For this purpose a high dose of the cholinergic agonist, physostigmine (1 drop 8 mg/ml alternate hours) was used. However, the effects on IOP of the two drugs were mainly additive most likely due to a short-lasting effect of physostigmine on the ciliary muscle.

    The progressive IOP reduction by physostigmine in the second study raised the question as to whether the drug reduces aqueous flow apart from enhancing outflow. On the contrary, in the third study repeated administrations of physostigmine, in 20 normal subjects, increased aqueous flow, measured with fluorophotometry, by about 25%.

    From studies of patients it is known that latanoprost twice daily has less ocular hypotensive effect than once daily. This was the subject of the two remaining studies. The possibility that latanoprost causes a short-lasting increase in aqueous flow was examined in 18 healthy volunteers. Application of a second drop in the morning would blunt some of the early IOP lowering effect of latanoprost. Once or twice daily applications had similar effect on aqueous flow, a tendency to an increase without any difference between the dose regimens. The next study confirmed the difference in effect on IOP between once and twice daily applications in 40 normal subjects. The difference remained even when one of the two applications was omitted after two weeks’ treatment. The results indicate that applying latanoprost twice daily induces a modest receptor desensitisation.

  • 170.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Therapeutic potential of prostaglandin analogues in glaucoma2001In: Expert Opinion on Investigational Drugs, ISSN 1354-3784, E-ISSN 1744-7658, Vol. 10, no 4, p. 679-694Article in journal (Refereed)
    Abstract [en]

    One of the most recent contributions to the therapeutic arsenal available for the treatment of glaucoma is the prostaglandin (PG) analogues. They represent a new class of ocular hypotensive drugs, targeting the uveoscleral outflow of ocular aqueous humour. Two drugs, latanoprost and unoprostone, are presently commercially available. In terms of intraocular pressure (IOP) reduction, latanoprost is the most powerful drug in clinical use today. The once daily dosing promotes compliance. Additional effect is achieved in combination with other hypotensive drugs, including those that increase trabecular outflow facility. The most frequent side effect is increased iris pigmentation that seems to be irreversible. A low frequency of cystoid macular oedema has been reported, predominantly in patients whose blood-retinal barrier (BRB) is compromised. Systemic side effects are rare. The experience with unoprostone is still much less than that with latanoprost. The ocular hypotensive mechanism of action of unoprostone is not well documented but an increase in uveoscleral outflow may be at least a part of its mode of action. Systemic side effects are rare and the ocular side effects seem to be mild. The ocular hypotensive effect is less than that of latanoprost and may not be suitable for monotherapy. It is widely accepted that the IOP alone is not responsible for the development of glaucomatous visual defects. It remains to be seen if this class of drugs will preserve vision in glaucoma patients better than other classes. More PG analogues are under development for potential clinical use.

  • 171.
    Lindén, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Alm, Albert
    Department of Neuroscience, Ophthalmology, Uppsala University.
    Acetylsalicylic acid does not reduce the intraocular pressure variation in ocular hypertension or glaucoma2000In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 70, no 3, p. 281-283Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to measure if intraocular pressure (IOP) and IOP variations in patients with ocular hypertension and glaucoma are decreased by acetylsalicylic acid (ASA). The hypothesis to be tested was that short-term fluctuations in the IOP are caused by breaks of the inner wall of Schlemm's canal that are repaired by platelets inducing a cycle of breaks and repair. Furthermore, prostaglandins affect uveoscleral outflow and ASA inhibits prostaglandin biosynthesis and platelet aggregation. This implies that ASA may have complex effects on the IOP and its variations.In 28 patients with ocular hypertension or glaucoma the IOP was measured seven times during 2 hr on two succeeding days. Five hundred mg ASA or placebo was administrated orally in a masked fashion 15 hr prior to the second session. After wash-out, this procedure was repeated with a cross-over design. The same study outline was used in 28 glaucoma patients except for the cross-over design. There were no statistically significant differences in the mean IOP or in the IOP variations between the placebo treated and the ASA treated eyes in either group, and there were no significant differences between the day before and after treatment in any group. The results suggest that ASA does not affect IOP variations in a clinically significant way and that a single dose of ASA has no significant effect on mean IOP.

  • 172.
    Lindén, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Alm, Albert
    Oftalmiatrik, Uppsala universitet.
    Prostaglandin analogues in the treatment of glaucoma1999In: Drugs & Aging, ISSN 1170-229X, E-ISSN 1179-1969, Vol. 14, no 5, p. 387-398Article in journal (Refereed)
    Abstract [en]

    Prostaglandin (PG) analogues are a new class of ocular hypotensive drugs that have been developed for the treatment of open angle glaucoma. Two of these drugs, latanoprost and unoprostone, are presently commercially available. Latanoprost was introduced in 1996 in the US and Europe. Presently it enjoys the most widespread use and is the most well documented drug of this group. It reduces the intraocular pressure (IOP) by a mechanism of action different from other drugs; namely by increasing the uveoscleral outflow. The aqueous inflow is not affected. The optimal dose regimen is one drop of 50 microg/ml once daily, which reduces the IOP by approximately 30% in patients with glaucoma. A more pronounced ocular hypotensive effect is demonstrated when latanoprost is combined with other glaucoma therapies, including beta-blockers, adrenergic and cholinergic agonists or carbonic anhydrase inhibitors. Latanoprost is well tolerated. The drug reaches a plasma concentration below that needed for stimulation of the FP-receptor, which may explain its favourable systemic tolerability profile. The major ocular adverse effect is increased iris pigmentation, which is due to increased synthesis of melanin in the melanocytes of the iris stroma. It is most frequently seen in green-brown eyes and it is probably permanent. A low frequency of cystoid macular oedema has also been reported, predominantly in predisposed eyes. Unoprostone was launched in Japan in 1994, but there is little experience with this drug outside the Japanese market and the documentation is more limited. Its main mechanism of action is on outflow, but this is not yet fully elucidated. The recommended dosage regimen is 1 drop of 1.2 mg/ml twice daily. No comparative studies in humans between the 2 drugs have yet been published.

  • 173.
    Lindén, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Alm, Albert
    Department of Ophthalmology, Uppsala University Hospital.
    The effect on intraocular pressure of latanoprost once or four times daily2001In: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079, Vol. 85, no 10, p. 1163-1166Article in journal (Refereed)
    Abstract [en]

    AIMS: To compare the effect on intraocular pressure (IOP) of latanoprost applied once daily with four times daily and to study if the difference persisted when treatment changed to once daily. METHODS: IOP was followed in 28 healthy volunteers in a double masked randomised 52 day study. Latanoprost 50 microg/ml was administered once daily in one eye and four times daily in the other during 2 weeks. Subsequently both eyes received one daily drop for 2 weeks. After another 3 weeks without treatment, a single drop was instilled in each eye. RESULTS: The IOP reduction on days 2 and 3 was greater in the eyes treated with four daily doses (p<0.01). During the following period there were no statistically significant differences between the eyes. After 3 weeks without treatment the IOP was lower than pretreatment (p<0.001). A single dose of latanoprost on day 50 resulted in a similar decrease in IOP in both eyes. Transient photophobia, mild flare, and/or a few cells occurred in 15 subjects. Two subjects were withdrawn because of photophobia and/or signs of anterior uveitis. CONCLUSION: Latanoprost four times daily caused an IOP reducing effect which was similar to once daily dosing, except for the first 2 days of treatment when it was more effective. Transient photophobia, cells, and flare were common during the four dose regimen, but resolved spontaneously without cessation of treatment.

  • 174.
    Lindén, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    [A national quality registry for refractive surgery is needed]2008In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, no 26-27, p. 1915-6Article in journal (Other (popular science, discussion, etc.))
  • 175.
    Lindén, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Bengtsson, Boel
    Alm, Albert
    Calissendorff, Berit
    Eckerlund, Ingemar
    Heijl, Anders
    Glaucoma management in Sweden: results from a nationwide survey2013In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 91, no 1, p. 20-24Article in journal (Refereed)
    Abstract [en]

    Purpose: To report the results from a nationwide survey on glaucoma management in Sweden, performed as a part of an Open Angle Glaucoma project conducted by the Swedish Council on Health Technology Assessment 2004-2008. Methods:  In 2005, a survey was distributed to all providers of glaucoma care in Sweden: public eye departments, public outpatient departments and private practices. The questionnaire included questions on number of examined patients, types of examinations during one defined week, internal organization and access to diagnostic equipment. The questionnaire was endorsed by the Swedish Ophthalmological Society. Reminders were sent out to nonresponders. Results:  Response rate was high; 97% (33/34) of eye departments, 85% (39/46) of outpatient departments and 55% (69/125) of private practices. Out of 29 282 visits in ophthalmic care during the study week, 7737 (26%) were related to glaucoma. Diagnostic equipment was generally available; all public eye facilities and 92% of private practices had at least one computerized perimeter, while equipment for fundus photography/imaging was available at 100% of eye departments, 82% of outpatient departments and 62% of private practices. The number of visual field tests and fundus images was rather low. Survey results indicate that patients on the average underwent bilateral field testing every 2nd year and fundus imaging every 8th year. Conclusion:  Glaucoma care generated about a quarter of all patient visits in Swedish ophthalmic care. Access to diagnostic facilities was good. To meet modern standards of glaucoma care, glaucoma damage must be measured and followed more closely than at the time of the survey.

  • 176.
    Lindén, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Johansson, Elias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Östlund, Fanny
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Normal-Tension Glaucoma Has Normal Intracranial Pressure: A Prospective Study of Intracranial Pressure and Intraocular Pressure in Different Body Positions2018In: Ophthalmology (Rochester, Minn.), ISSN 0161-6420, E-ISSN 1549-4713, Vol. 125, no 3, p. 361-368Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To test the hypothesis that normal-tension glaucoma (NTG) is caused by an increased pressure difference across the lamina cribrosa (LC) related to a low intracranial pressure (ICP).

    DESIGN: Prospective case-control study.

    PARTICIPANTS: Thirteen NTG patients (9 women; median 71 [range: 56-83] years) were recruited for investigation with the same protocol as 11 healthy volunteers (8 women; 47 [30-59] years). A larger control group (n = 51; 30 women; 68 [30-81] years) was used only for ICP comparison in supine position.

    METHODS: ICP and intraocular pressure (IOP) were simultaneously measured in supine, sitting, and 9° head-down tilt (HDT) positions. Trans-lamina cribrosa pressure difference (TLCPD) was calculated using ICP and IOP together with geometric distances estimated from magnetic resonance imaging to adjust for hydrostatic effects.

    MAIN OUTCOME MEASURES: ICP, IOP, and TLCPD in different body positions.

    RESULTS: Between NTG patients and healthy volunteers, there were no differences in ICP, IOP, or TLCPD in supine, sitting, or HDT (P ≥ 0.11), except for IOP in HDT (P = 0.04). There was no correlation between visual field defect and TLCPD, IOP, or ICP and in any body position (P ≥ 0.39). Mean ICP in supine was 10.3 mmHg (SD = 2.7) in the NTG group (n = 13) and 11.3 (2.2) mmHg in the larger control group (n = 51) (P = 0.24).

    CONCLUSIONS: There was no evidence of reduced ICP in NTG patients as compared with healthy controls, either in supine or in upright position. Consequently, the hypothesis that NTG is caused by an elevated TLCPD from low ICP was not supported.

  • 177.
    Lindén, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Johansson, Elias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Östlund, Fanny
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Re: Linden et al.: Normal-tension glaucoma has normal intracranial pressure: a prospective study of intracranial pressure and intraocular pressure in different body positions (Ophthalmology. 2018;125:361-368) REPLY2018In: Ophthalmology (Rochester, Minn.), ISSN 0161-6420, E-ISSN 1549-4713, Vol. 125, no 6, p. e43-e44Article in journal (Refereed)
  • 178.
    Lindén, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Johansson, Elias
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Östlund, Fanny
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Re: Linden et al.: Normal-tension glaucoma has normal intracranial pressure: a prospective study of intracranial pressure and intraocular pressure in different body positions (Ophthalmology. 2018;125:361-368) REPLY2018In: Ophthalmology (Rochester, Minn.), ISSN 0161-6420, E-ISSN 1549-4713, Vol. 125, no 10, p. E74-E75Article in journal (Refereed)
  • 179.
    Lithén, Pontus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    The development of corneal spherical aberration during childhood and adolescence2015Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 180.
    Liu, Jing-Xia
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Andersen, Peter M
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Different impact of ALS on laminin isoforms in human extraocular muscles versus limb muscles2011In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 52, no 7, p. 4842-4852Article in journal (Refereed)
    Abstract [en]

    Purpose. To determ ine the impact of amyotrophic lateral sclerosis (ALS) on the extraocular muscles (EOMs) by examining the laminin isoform composition of the basement membranes (BMs) in EOMs and limb muscles from donors with ALS.

    Methods. Muscle samples collected at autopsy from ALS donors and from transgenic mice overexpressing human SOD1 mutations (D90A or G93A), and age-matched controls were analyzed with immunohistochemistry using antibodies against laminin chain α2 (Lnα2), Lnα4, Lnα5, Lnβ1, Lnβ2 and Lnγ1. Neuromuscular junctions (NMJs) were identified with α-bungarotoxin.

    Results. Lnα2, the hallmark chain of skeletal muscle, and Lnβ2 were absent or partially absent from the BMs in a variable number of muscle fibers in most of the ALS EOMs. Three ALS donors showed dramatic decrease in the levels of these chains around their muscle fibers and NMJs. Changes in Lnα2 were not age-related and were also present in EOMs of ALS mouse models. Lnα4 was preserved in the majority of NMJs in EOM but absent in the majority of NMJs in limb muscle of ALS. The BMs around muscle fibers, NMJs, nerves and blood vessels of the majority of EOMs of ALS donors had rather normal appearance and laminin composition, but heterogeneity was observed among EOM samples of individual ALS donors and between ALS donors.

    Conclusions. The present study showed distinct impact of ALS on EOMs as compared to limb muscles. The EOMs maintained a normal laminin composition in their NMJs which may be instrumental for the fact that they are not typically affected in ALS.

  • 181.
    Liu, Jing-Xia
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Andersen, Peter M
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Distinct changes in synaptic protein composition at neuromuscular junctions of extraocular muscles versus limb muscles of ALS donors2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 2, p. e57473-Article in journal (Refereed)
    Abstract [en]

    The pathophysiology of amyotrophic lateral sclerosis (ALS) is very complex and still rather elusive but in recent years evidence of early involvement of the neuromuscular junctions (NMJs) has accumulated. We have recently reported that the human extraocular muscles (EOMs) are far less affected than limb muscles at the end-stage of ALS from the same donor. The present study aimed to compare the differences in synaptic protein composition at NMJ and in nerve fibers between EOM and limb muscles from ALS donors and controls. Neurofilament light subunit and synaptophysin decreased significantly at NMJs and in nerve fibers in limb muscles with ALS whereas they were maintained in ALS EOMs. S100B was significantly decreased at NMJs and in nerve fibers in both EOMs and limb muscles of ALS donors, but other markers confirmed the presence of terminal Schwann cells in these NMJs. p75 neurotrophin receptor was present in nerve fibers but absent at NMJs in ALS limb muscles. The EOMs were able to maintain the integrity of their NMJs to a very large extent until the end-stage of ALS, in contrast to the limb muscles. Changes in Ca2+ homeostasis, reflected by altered S100B distribution, might be involved in the breakdown of nerve-muscle contact at NMJs in ALS.

  • 182.
    Liu, Jing-Xia
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Eriksson, Per-Olof
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Myosin heavy chain composition of muscle spindles in human biceps brachii2002In: Histochem Cell Biol, Vol. 50, no 2, p. 171-184Article in journal (Refereed)
    Abstract [en]

    Data on the myosin heavy chain (MyHC) composition of human muscle spindles are scarce in spite of the well-known correlation between MyHC composition and functional properties of skeletal muscle fibers. The MyHC composition of intrafusal fibers from 36 spindles of human biceps brachii muscle was studied in detail by immunocytochemistry with a large battery of antibodies. The MyHC content of isolated muscle spindles was assessed with SDS-PAGE and immunoblots. Four major MyHC isoforms (MyHCI, IIa, embryonic, and intrafusal) were detected with SDS-PAGE. Immunocytochemistry revealed very complex staining patterns for each intrafusal fiber type. The bag(1) fibers contained slow tonic MyHC along their entire fiber length and MyHCI, alpha-cardiac, embryonic, and fetal isoforms along a variable part of their length. The bag(2) fibers contained MyHC slow tonic, I, alpha-cardiac, embryonic, and fetal isoforms with regional variations. Chain fibers contained MyHCIIa, embryonic, and fetal isoforms throughout the fiber, and MyHCIIx at least in the juxtaequatorial region. Virtually each muscle spindle had a different allotment of numbers of bag(1), bag(2) and chain fibers. Taken together, the complexity in intrafusal fiber content and MyHC composition observed indicate that each muscle spindle in the human biceps has a unique identity.

  • 183.
    Liu, Jing-Xia
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    A novel type of multiterminal motor endplate in human extraocular muscles2018In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 1, p. 539-548Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the relation between type of motor endplate, acetylcholine receptor (AChR) subunit composition, and fiber types in human extraocular muscles (EOMs).

    Methods: EOM samples collected from subjects aged 34 to 82 years were serially sectioned and processed for immunohistochemistry, with specific antibodies against different myosin heavy chain (MyHC) isoforms, neurofilament, synaptophysin, and adult epsilon (ε) and fetal gamma (γ) AChR subunits as well as α-bungarotoxin.

    Results: A novel type of motor endplate consisting of large, multiterminal en plaque endings was found in human EOMs, in addition to the previously well-described single en plaque and multiple en grappe endplates. Such novel endplates were abundant but exclusively observed in myofibers lacking MyHC slow and fast IIa but containing MyHC extraocular (MyHCeom), isoforms. Multiple en grappe endings were found only in myofibers containing MyHC slow-tonic isoform and contained fetal γ AChR subunit. Adult ε and fetal γ AChR subunits, alone or combined, were found in the multiterminal endplates. Distinct AChR subunits were present in adjacent motor endplates of a given myofiber containing MyHCeom.

    Conclusions: Human EOMs have a more complex innervation pattern than previously described, comprising also a novel type of multiterminal motor endplate present in myofibers containing MyHCeom. The heterogeneity in AChR subunit composition in a given myofiber suggests the possible presence of polyneuronal innervation in human EOMs.

  • 184.
    Liu, Jing-Xia
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Muscle spindles in the deep muscles of the human neck: a morphological and immunocytochemical study2003In: Journal of Histochemistry and Cytochemistry, ISSN 0022-1554, E-ISSN 1551-5044, Vol. 51, no 2, p. 175-186Article in journal (Refereed)
    Abstract [en]

    Muscle spindle density is extremely high in the deep muscles of the human neck. However, there is a paucity of information regarding the morphology and immunoreactivity of these muscle spindles. The objective of this study was to investigate the intrafusal fiber content and to assess the myosin heavy chain (MyHC) composition of muscle spindles from human deep neck muscles. In addition to the conventional spindles containing bag(1), bag(2), and chain fibers (b(1)b(2)c spindle), we observed a number of spindles lacking bag(1) (b(2)c spindle) or bag(2) (b(1)c spindle) fibers. Both bag(1) and bag(2) fibers contained slow tonic MyHCs along their entire fiber length and MyHCI, MyHCIIa, embryonic, and alpha-cardiac MyHC isoforms along a variable length of the fibers. Fetal MyHC was present in bag(2) fibers but not in bag(1) fibers. Nuclear chain fibers contained MyHCIIa, embryonic, and fetal isoforms with regional variations. We also compared the present data with our previous results obtained from muscle spindles in human biceps brachii and the first lumbrical muscles. The allotment of numbers of intrafusal fibers and the MyHC composition showed some muscle-related differences, suggesting functional specialization in the control of movement among different human muscles.

  • 185.
    Liu, Jing-Xia
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Willison, Hugh J
    Pedrosa-Domellof, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Immunolocalisation of GQ1b and related gangliosides in human extraocular neuromuscular junctions and muscle spindles2009In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 50, no 7, p. 3226-3232Article in journal (Refereed)
    Abstract [en]

    Purpose: To examine the distribution of anti-GQ1b, -GT1a and -GD1b antibody binding in human extraocular muscles (EOMs), axial and limb muscles and muscle spindles and thereby test the hypothesis that their distinctive ganglioside composition provides the molecular basis for selective involvement of EOMs and muscle spindles in Miller Fisher syndrome.

    Methods: Muscle samples from adult human EOMs, vastus lateralis, biceps brachii, lumbrical, psoas and deep muscles of the neck were processed for immunohistochemistry, with monoclonal antibodies against ganglioside GQ1b, GT1a and GD1b. Neuromuscular junctions (NMJs) were detected by a-bungarotoxin binding and by acetycholinesterase reaction.

    Results: The vast majority of motor endplates of human EOMs richly bound anti-GQ1b, -GT1a, and -GD1b ganglioside antibodies. Anti-GQ1b, -GT1a, and -GD1b ganglioside antibody bindings to NMJs in human limb and axial muscle were very scarce but the nerve terminals inside muscle spindles and in direct contact with intrafusal fibers were labeled with anti- GQ1b, -GT1a and -GD1b ganglioside antibodies.

    Conclusions: The abundant and synaptic-specific binding of anti-GQ1b, -GT1a, and -GD1b ganglioside antibodies and the rich capillary supply in the human EOMs may partly explain the selective paralysis of these muscles in Miller Fisher syndrome.

  • 186.
    Lundberg, Björn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Safety and efficacy of intracameral mydriatics in cataract surgery2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: In order to perform cataract surgery, adequate dilatation of the pupil is essential. This is traditionally achieved by preoperative topical mydriatic eye-drops, commonly cyclopentolate and phenylephrine. This routine has several disadvantages. First, the slow penetration through the cornea delays the onset of mydriasis. Second, the limited bioavailability of topically administered substances with significant systemic absorption may increase the risk for systemic side effects. Third, even if good mydriasis is achieved initially with topical mydriatics (TM), the effect tends to wear off during surgery. In relation to cataract surgery a transient postoperative corneal oedema is sometimes noted, indicating effects on the corneal endothelial pump function. These effects have been ascribed to ultrasonic or mechanical trauma from the phacoemulsification procedure. Corneal endothelial cell loss (ECL) is a commonly studied variable, not least because it is associated with the long-term risk for corneal decompensation. But, there has been a debate whether postoperative corneal swelling after phacoemulsification cataract surgery correlates to ECL.

    Aims: To evaluate an alternative mydriatic regimen for phacoemulsification cataract surgery: intracameral injection of mydriatics mixed with lidocaine (ICM). Additionally, to determine the correlation between early transient postoperative corneal oedema and permanent ECL after phacoemulsification cataract surgery.

    Methods: Pupil dilatation with ICM (150 µl of lidocaine 1%, phenylephrine 1.5%, and cyclopentolate 0.1%) was compared to TM (phenylephrine 10% and cyclopentolate 1%) prior to cataract surgery. Additionally, two ICM-groups were randomized to receive either 0.6 µg/ml epinephrine added to the irrigating balanced salt solution or no epinephrine in the irrigation solution. Furthermore, two randomized ICM-groups, with or without cyclopentolate, were analyzed. The patients planned for cataract surgery were examined with ultrasonic pachymetry, specular microscope endothelial photography and Orbscan II slit-scan tomography pre- and postoperatively.

    Results: With ICM, mydriasis reached 95 ± 3% of its final value within 20 seconds. In the ICM-group, the pupils were smaller than in the TM-group (mean 6.7 ± 1.0 mm versus 7.7 ± 1.0 mm, P<.001), but did not contract intraoperatively as the TM pupils did. Conversely, with ICM the pupil sizes generally increased during the cataract procedures. This increase was significantly greater without epinephrine in the irrigating solution (13 ± 19% versus 4 ± 14%; p = 0.02). No significant differences in pupil sizes were observed between the patients who were given ICM with or without cyclopentolate. The central corneal swelling at the first postoperative day was strongly correlated to the central ECL at 3 months, R2 = 0.785, P < 0.001.

    Conclusions: ICM is a rapid and safe alternative to TM in phacoemulsification cataract surgery. An irrigating solution without epinephrine can safely be used with ICM. Cyclopentolate, administrated intracamerally, has no immediate additive mydriatic effect to intracameral lidocaine combined with phenylephrine. The degree of permanent corneal endothelial damage in cataract surgery is reflected in the degree of early postoperative corneal swelling.

  • 187.
    Lundberg, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Intracameral mydriatics in phacoemulsification cataract surgery.2003In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 29, no 12, p. 2366-2371Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate intracameral injection of mydriatics in phacoemulsification cataract surgery and compare the results with those of conventional topical mydriatics. SETTING: Department of Clinical Science/Ophthalmology, Umeå University Hospital, Umeå, Sweden. METHODS: This prospective randomized double-blind study included 60 patients who were given topical (topical group) or intracameral (intracameral group) mydriatics. The topical mydriatics comprised 3 drops of cyclopentolate 1% and phenylephrine 10% given 15 minutes apart and 150 microL intracameral lidocaine hydrochloride 1% (Xylocaine) and the intracameral mydriatics, placebo eyedrops and 150 microL intracameral cyclopentolate 0.1%, phenylephrine 1.5%, and Xylocaine 1%. The pupil size was recorded preoperatively, throughout surgery, and 1 day and 1 month postoperatively. Preoperative and postoperative corneal endothelial morphology, corneal thickness, intraocular pressure, visual acuity, aqueous cells and flare, phacoemulsification energy, duration of surgery, pulse, blood pressure, and intraoperative sensation of pain and glare were also recorded. RESULTS: With intracameral mydriatics, mydriasis reached 95% +/- 3% (SD) of its final value within 20 seconds. In the intracameral group, the pupils were smaller than in the topical group (mean 6.7 +/- 1.0 mm versus 7.7 +/- 1.0 mm, P<.001) but did not contract intraoperatively. The pupils in the topical group tended to contract, and the difference between groups was significant (P =.0020). The intracameral group reported less glare during the procedure (P<.001). There was no difference in endothelial cell loss, inflammatory reaction, postoperative corneal swelling, or surgical performance between the groups. CONCLUSIONS: Intracameral mydriatics were a rapid, effective, and safe alternative to topical mydriatics in phacoemulsification. Their use can simplify preoperative routines and in certain high-risk groups, may reduce the risk for cardiovascular side effects.

  • 188.
    Lundberg, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Intracameral mydriatics in phacoemulsification cataract surgery - a 6-year follow-up2013In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 91, no 3, p. 243-246Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate the long-term safety of intracameral mydriatics (ICM) in phacoemulsification cataract surgery compared with conventional topical mydriatics (TM). Methods: A total of 45 patients were examined 6 years after phacoemulsification cataract surgery. The patients had previously participated in a prospective randomized double-blind study including 60 patients, operated with either ICM or TM. The follow-up included best-corrected visual acuity (BCVA), intraocular pressure (IOP), grade of posterior capsule opacification (PCO), YAG laser capsulotomy rate, pupil size, corneal thickness and endothelial morphology. Results: No differences in postoperative BCVA, IOP, pupil size, PCO or YAG rate were observed between the groups. Endothelial cell loss, endothelial morphology and corneal thickness were also equivalent. Conclusions: Intracameral mydriatics is a safe alternative to topical mydriatics in phacoemulsification cataract surgery with no long-term disadvantages at 6-year follow-up.

  • 189.
    Lundberg, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Intracameral mydriatics in phacoemulsification surgery obviate the need for epinephrine irrigation.2007In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 85, no 5, p. 546-550Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate the possibility of removing epinephrine from the irrigating solution in phacoemulsification surgery when using intracameral mydriatics (ICMs). METHODS: We carried out a prospective, randomized, double-blinded study of 140 patients with age-related cataracts, scheduled for unilateral phacoemulsification. The first part of the study involved 90 patients divided into two groups. Patients in both groups were given 150 microl ICMs at the beginning of the procedure. In group 1, 0.6 microg/ml epinephrine was added to the irrigating balanced salt solution. No epinephrine was added to the irrigation solution used in group 2. The second part of the study involved 50 patients, all of whom were given topical mydriatics (TMs) and then similarly divided into two groups and treated as in the first study setting. RESULTS: With ICMs, pupil sizes generally increased during the procedures. Remarkably, this increase was significantly greater without epinephrine (13 +/- 19% versus 4 +/- 14%; p = 0.02). In the TMs setting, pupil sizes decreased intraoperatively in both groups; significantly more without epinephrine (- 5 +/- 4% versus - 12 +/- 7%; p < 0.001). CONCLUSIONS: An irrigating solution without epinephrine can safely be used with ICMs. The increase in pupil size during the procedure is greater without epinephrine. This study also confirms earlier findings that epinephrine is beneficial when using TMs.

  • 190.
    Lundberg, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Preoperative topical cyclopentolate can be omitted when using intracameral lidocaine in phacoemulsification surgery2009In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 87, no 3, p. 297-299Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate the mydriatic effect of topical cyclopentolate 1% when combined with topical phenylephrine 10% and intracameral lidocaine 1% in phacoemulsification cataract surgery.

    METHODS: We performed a prospective, double-masked, randomized trial including 20 patients with age-related cataract, who were scheduled for unilateral phacoemulsification and intraocular lens (IOL) implantation. Patients were given either two drops of phenylephrine 10% at 30 mins and 15 mins prior to surgery (group 1), or two drops each of cyclopentolate 1% and phenylephrine 10% at the same time points (group 2). All patients were also given lidocaine 1% intracamerally at the beginning of the procedure. Intraoperative pupil sizes were assessed from video-recordings.

    RESULTS: Initially, pupil sizes were significantly smaller in group 1 (4.8 +/- 1.2 mm versus 6.5 +/- 1.4 mm; p = 0.0098), but the lidocaine injection increased the pupil sizes in group 1 significantly, so that pupil sizes in both groups were equalized throughout the surgical procedure.

    CONCLUSIONS: Preoperative topical cyclopentolate does not enhance mydriasis in phacoemulsification surgery when using intracameral lidocaine and can be omitted when intracameral lidocaine is used.

  • 191.
    Lundberg, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Separate and additive mydriatic effects of lidocaine hydrochloride, phenylephrine, and cyclopentolate after intracameral injection.2008In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 34, no 2, p. 280-283Article in journal (Refereed)
  • 192.
    Lundberg, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders B
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    The mydriatic effect of intracameral epinine hydrochloride2009In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 50, no 11, p. 5336-5338Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To compare the mydriatic effect and the short-term corneal endothelial safety of intracamerally injected N-methyl-3,4-dihydroxyphenylamine (epinine) to phenylephrine in a porcine eye model.

    METHODS. One hundred and twelve eyes from newly slaughtered pigs were used in this study. After pretreatment with 20 mg of intracameral acetylcholine to give miosis, 0.15 ml of epinine or phenylephrine 0.3%, 1.5% or 3.0% was given as an intracameral injection. The pupils were filmed during 90 seconds with a video camera connected to an operation microscope, and the mean pupil diameters were measured from the video recordings. In 37 additional eyes, 0.15 ml of the vehicle, 1.5% epinine or 1.5% phenylephrine was injected intracamerally, and the eyes were kept on ice overnight. Corneal endothelial morphology was assessed before and after the treatment. Ten eyes were given no injection and served as controls.

    RESULTS. Epinine had a significantly larger mydriatic effect than phenylephrine at equal concentrations. The endothelial cell loss was equal with both substances, and did not exceed that of the vehicle.

    CONCLUSIONS. Epinine was a more potent mydriatic than phenylephrine in this porcine eye model. The porcine eye model appears suitable as a first efficacy screening of substances for intraocular use. Epinine is a promising candidate substance for intraoperative intracameral use in humans, for example in cataract surgery.

  • 193.
    Lundberg, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Jonsson, Maria
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Postoperative corneal swelling correlates strongly to corneal endothelial cell loss after phacoemulsification cataract surgery.2005In: American Journal of Ophthalmology, ISSN 0002-9394, E-ISSN 1879-1891, Vol. 139, no 6, p. 1035-1041Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate postoperative corneal swelling as a predictor of corneal endothelial cell loss after phacoemulsification cataract surgery. DESIGN: Prospective observational case series. METHODS: Thirty patients planned for routine phacoemulsification cataract surgery were included. Ultrasonic pachymetry and specular microscope endothelial photography of the central and nasal portions of the cornea and Orbscan II slit-scan tomography were performed preoperatively and the day after surgery. The 30 patients were selected from 41 patients based on their increase in central corneal thickness: the first 10 cases with a <5% increase, the first 10 with a 6% to 20% increase, and the first 10 with a > or =20% increase. The same measurements were repeated after 1, 2, and 3 months. The primary outcome measures were corneal endothelial cell loss and increase in pachymetry. Several other parameters were also registered, including age, degree of cataract, visual acuity, phacoemulsification time and energy, total operation time, and the amount of infusion fluid used. RESULTS: The central corneal swelling at postoperative day 1 was strongly correlated with the central corneal endothelial cell loss at 3 months (R(2) = 0.785, P < .001). CONCLUSIONS: In this series, with large variations in the corneal swelling at the first postoperative day, the degree of permanent corneal endothelial damage was reflected in the degree of early postoperative corneal swelling. Measuring the difference in pachymetry at postoperative day 1 is a useful way to assess the effects on the corneal endothelium exerted by the phacoemulsification procedure.

  • 194.
    Lundqvist, Britta
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Long-term outcome after cataract surgery: a longitudinal study2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background Cataract surgery is the most common surgical procedure carried out in the developed world and surgery volumes have increased considerably during the last decades. Various aspects of the surgical procedure, including surgical incision size and intraocular lens materials, have changed substantially, improving the safety and the quality of the outcome. Previous research has primarily focused on the visual function results with a short follow-up time. Long-term population-based studies, exceeding a few years, presenting visual functional results postoperatively, have not been published.

    Aims To determine the effects of cataract surgery on subjectively experienced visual function and visual acuity in a defined population, and compare the results between sub-groups, on a long-term basis.

    Methods In this prospective, population-based investigation, all patients with presenile and senile cataract (n=810), operated on during a one-year period (1997-98), at Umeå University Hospital were included. The frequency of cataract surgery at that time, was 5.2 per 1000 population studied. Visual acuity was tested and an eye examination was performed before surgery, 4-8 weeks postoperatively, and five and ten years after surgery. Subjective visual function was assessed using self-administered questionnaires (VF-14) at all occasions. Statistical evaluations comprised analyses of variance, Mann-Whitney U-test, chi-square test, multiple linear regression, a life-table calculation, and Cox’s proportional hazard model.

    Results Five years after cataract surgery, subjective and objective visual function remained stable in most patients. The most frequent cause of deterioration of visual acuity and decrease in VF-14 scores was agerelated macular degeneration (ARMD). Two thirds of the patients in the cohort were women. They were significantly older than the men and more often operated on both eyes. After adjustment for age and visual acuity, women cataract surgery patients assessed their visual function worse than men both before surgery and 4 months postoperatively. Five years after surgery these differences were no longer significant. At baseline, 13% of the patients were diabetics. At the five-year followup, subjective and objective visual function remained stable in most surviving diabetics, and the longitudinal visual function was not significantly worse compared with the non-diabetics. Ten years after surgery, 28% had received treatment for posterior capsular opacification (PCO). A significantly larger proportion of patients less than 65 years at surgery (37%) compared with those 65 years or older (20%) had been treated.

    Conclusions Most patients sustain their level of visual acuity and visual function also five and ten years after cataract surgery. Ocular co-morbidity, such as ARMD, is the major cause of longitudinally reduced visual function. Patients suffering from diabetes did not have a significantly worse visual function after five years. A surprisingly large proportion of patients had received treatment for PCO after ten years.

  • 195.
    Lundqvist, Britta
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Mönestam, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Gender-related differences in cataract surgery outcome: a 5-year follow-up2008In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 86, no 5, p. 543-548Article in journal (Refereed)
    Abstract [en]

    PURPOSE: A prospective, longitudinal, population-based cohort study was performed to analyse gender-related differences in subjective and objective visual function 5 years after cataract surgery.

    METHODS: All patients (n = 810) who underwent cataract surgery during a 1-year period (1997-98) at Norrlands University Hospital in Umeå, Sweden, were studied with visual acuity (VA) data and questionnaires (VF-14) before and after surgery, as well as 5 years later. Five hundred and thirty patients (177 men, 353 women) answered the questionnaire, constituting 90% (530/590) of the survivors. Four hundred and sixty-seven (156 men, 311 women) also underwent an eye examination.

    RESULTS: The women were significantly older (P = 0.009) and were more often operated on both eyes (P = 0.005). Before surgery and postoperatively, the women had a significantly lower age- and VA-adjusted VF-14 score (P = 0.000 and P = 0.036, respectively). This difference was not significant 5 years after surgery (P = 0.16). Five years after surgery, a significantly larger proportion of women had a decline of more than 0.1 logarithm of the minimum angle of resolution of the better-seeing eye (P = 0.013). There were no significant gender-related differences in the operated eye.

    CONCLUSION: Female cataract surgery patients assess their visual function worse than males after adjustment for age and VA preoperatively and postoperatively. These differences were not significant 5 years after surgery although the men had better best-corrected visual acuity (BCVA) of their better eye. It is important to be aware of gender-related differences in perception when performing questionnaire-based outcome studies.

  • 196.
    Lundqvist, Britta
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Mönestam, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Longitudinal changes in subjective and objective visual function 5 years after cataract surgery: prospective population-based study2006In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 32, no 11, p. 1944-1950Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate the long-term outcomes of cataract surgery by analyzing data collected 5 years after surgery and comparing with preoperative and postoperative subjective and objective visual function results.

    SETTING: Norrlands University Hospital, Umeå, Sweden.

    METHODS: A prospective longitudinal population-based cohort study comprised 810 patients who had cataract surgery during a 1-year period within a geographically defined area. Evaluated were visual acuity data and Visual Function-14 questionnaire (VF-14) results before and after surgery. Five years later, the 590 patients still alive were offered eye examinations and asked to fill out the questionnaire.

    RESULTS: Of the 590 patients asked to participate at 5 years, 530 answered the questionnaire and 467 had eye examinations. The median VF-14 total score for all patients after surgery was 100; at 5 years, the score decreased to 96.7 (P = .001). Five years after surgery, 46% of patients had unchanged or better visual acuity in the operated eye, 37% had lost more than 0.1 logMAR unit, and 22% had a reduction in VF-14 score of 10 points or more. The two main reasons for the decline in visual acuity and VF-14 scores were age-related macular degeneration (ARMD) (47% and 60%, respectively) and glaucoma (12% and 11%, respectively). Age, co-morbidity, and VF-14 scores after surgery were independently associated with the VF-14 score 5 years after surgery.

    CONCLUSIONS: Subjective and objective visual function 5 years after cataract surgery remained stable in most patients. Co-morbidity, most commonly ARMD, was the most frequent cause of deterioration of visual acuity and decrease in VF-14 scores. Age and co-morbidity were independently associated with the VF-14 score 5 years after surgery.

  • 197.
    Lundqvist, Britta
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Mönestam, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Longitudinal changes in subjective and objective visual function in diabetics 5 years after cataract surgery.2012In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 90, no 3, p. 215-220Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate and compare the long-term subjective and objective visual functional results of phacoemulsification in diabetics and non-diabetics. Methods: A prospective, longitudinal, population-based study comprising 57 diabetics and 473 non-diabetics, who had cataract surgery during a 1-year period at Norrlands University Hospital, Umeå, Sweden. Visual acuity data, visual function questionnaire (VF-14) responses, and level of diabetic retinopathy were recorded pre- and postoperatively as well as 5 years after surgery. Results: Four months postoperatively, the median VF-14 total score for both the diabetics and the non-diabetics was 100; at 5 years, the score decreased to 96.4 and 97.2, respectively (p = 0.81). The median best corrected visual acuity (BCVA) of the operated eye was logMAR 0.046 (Q1:Q3 = 0:0.15) for both the diabetics and the non-diabetics 4-8 weeks postoperatively. Five years later, the BCVA for the diabetics was logMAR 0.14 (Q1:Q3 = 0.02:0.34) and for the non-diabetics 0.1 (Q1:Q3 = 0.02:0.3), (p = 0.34). Five years after surgery, 26% of the diabetics and 22% of the non-diabetics had a reduction in VF14-score of 10 points or more (p = 0.64) compared with 4 months postoperatively. One-third of both the diabetics (18/57) and the non-diabetics (149/473) had lost more than 0.1 log MAR unit in BCVA of the operated eye (p = 0.86). Conclusion: Subjective and objective visual function 5 years after cataract surgery remained stable in most surviving diabetics and non-diabetics. The longitudinal visual function in diabetics was not significantly worse compared with non-diabetics.

  • 198.
    Lundqvist, Britta
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Mönestam, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Longitudinal changes in subjective and objective visual function in diabetics 5 years after cataract surgery: Prospective population-based study.2006In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 32, no 11, p. 1944-1950Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate the long-term outcomes of cataract surgery by analyzing data collected 5 years after surgery and comparing with preoperative and postoperative subjective and objective visual function results. SETTING: Norrlands University Hospital, Umeå, Sweden. METHODS: A prospective longitudinal population-based cohort study comprised 810 patients who had cataract surgery during a 1-year period within a geographically defined area. Evaluated were visual acuity data and Visual Function-14 questionnaire (VF-14) results before and after surgery. Five years later, the 590 patients still alive were offered eye examinations and asked to fill out the questionnaire. RESULTS: Of the 590 patients asked to participate at 5 years, 530 answered the questionnaire and 467 had eye examinations. The median VF-14 total score for all patients after surgery was 100; at 5 years, the score decreased to 96.7 (P = .001). Five years after surgery, 46% of patients had unchanged or better visual acuity in the operated eye, 37% had lost more than 0.1 logMAR unit, and 22% had a reduction in VF-14 score of 10 points or more. The two main reasons for the decline in visual acuity and VF-14 scores were age-related macular degeneration (ARMD) (47% and 60%, respectively) and glaucoma (12% and 11%, respectively). Age, co-morbidity, and VF-14 scores after surgery were independently associated with the VF-14 score 5 years after surgery. CONCLUSIONS: Subjective and objective visual function 5 years after cataract surgery remained stable in most patients. Co-morbidity, most commonly ARMD, was the most frequent cause of deterioration of visual acuity and decrease in VF-14 scores. Age and co-morbidity were independently associated with the VF-14 score 5 years after surgery.

  • 199.
    Lundqvist, Britta
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Mönestam, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Ten-year longitudinal visual function and Nd: YAG laser capsulotomy rates in patients less than 65 years at cataract surgery2010In: American Journal of Ophthalmology, ISSN 0002-9394, E-ISSN 1879-1891, Vol. 149, no 2, p. 238-244Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate the longitudinal subjective and objective visual functional results in adult cataract patients younger than 65 years at surgery. To evaluate the 10-year cumulative incidence of neodymium-yttrium-aluminum-garnet (Nd:YAG) laser treatment.

    DESIGN: A prospective, longitudinal, population-based cohort study.

    METHODS: The study comprised 116 patients younger than 65 years who had cataract surgery during 1 year at Norrlands University Hospital, Umeå, Sweden. Most patients (94%) had received implantation with a hydrophobic acrylic intraocular lens. Evaluated were visual acuity (VA) and visual function questionnaire (VF-14) results before and after surgery. A comparison with patients 65 years or older at surgery was made. Ten years later, 102 survivors were offered eye examinations and again asked to fill out the questionnaire. Past Nd:YAG laser treatment, as well as high- and low-contrast VA results, were analyzed.

    RESULTS: Ten years postoperatively, 37% of the patients under 65 at surgery had been treated with Nd:YAG in comparison to 20% of the older patients. The cumulative incidence for not having Nd:YAG over 10 years was 72% for those under 65 and 85% for the patients 65 years or more at surgery. Eighteen percent of the younger patients had lost more than 0.1 logarithm of the minimal angle of resolution (logMAR) units of the operated eye, compared with 37% of the older (P = .00003). A reduction in VF-14 score of 10 points or more was found in 9% of the younger and 28% of the older cataract surgery patients (P = .00004).

    CONCLUSION: Ten years after surgery, subjective and objective visual function remained stable in most patients younger than 65 years at surgery. More than one-third had received a posterior capsulotomy. Only a few patients with posterior capsular opacification requiring Nd:YAG were untreated at the 10-year follow-up.

  • 200.
    Lundqvist, Oscar
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Posterior chamber injection of intracameral mydriatics increases the durability of the mydriatic response2013In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 91, no 7, p. 657-659Article in journal (Refereed)
    Abstract [en]

    Purpose:  To compare the mydriatic effect of intracameral mydriatics injected into the anterior or the posterior chamber in routine phacoemulsification cataract surgery. Methods:  Forty-four patients planned for unilateral phacoemulsification surgery were included after informed consent. Mydriasis was achieved by injecting 150 μl of a mixture of phenylephrine 1.5% and lidocaine 1.0% at the beginning of the procedure. The patients were randomly assigned to injection into the anterior or the posterior chamber. The pupils were filmed during the procedures, and the mean pupil diameters were measured at predetermined intervals from the video recordings by an independent observer. Results:  Immediately after the injection, the pupils were larger after posterior chamber injection (3.8 ± 0.8 versus 3.1 ± 0.7 mm; p = 0.004). A similar difference was seen after the phacoemulsification (6.4 ± 0.7 versus 5.9 ± 1.0 mm; p = 0.031). The mydriatic durability was also better after posterior injection (p = 0.004-0.041). Conclusions:  Apart from immediately after the injection, the initial mydriatic response was similar with both injection techniques, but the durability of the mydriasis was slightly better after a posterior chamber injection of ICM.

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