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  • 1.
    Alm, Albert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Grierson, Ian
    Shields, M. Bruce
    Side effects associated with prostaglandin analog therapy2008In: Survey of ophthalmology, ISSN 0039-6257, E-ISSN 1879-3304, Vol. 53, no Suppl. 1, p. S93-S105Article, review/survey (Refereed)
    Abstract [en]

    Topical prostaglandin analogs, which have become first-line therapy in the medical management of glaucoma, have an excellent safety profile with regard to systemic side effects, but are associated with several ocular side effects. Some of these are common, with no apparent serious consequences other than cosmetic, whereas others are much less common but represent potentially sight-threatening side effects. The former group includes conjunctival hyperemia, elongation and darkening of eyelashes, induced iris darkening, and periocular skin pigmentation. The latter group of side effects, which are relatively rare and lack definitive causal relationship to prostaglandin analog therapy, includes iris cysts, cystoid macular edema, anterior uveitis, and reactivation of herpes simplex keratitis. Most of the literature regarding side effects associated with prostaglandin analogs involves the use of latanoprost, probably because it was the first to be studied. There is no evidence, however, aside from less conjunctival hyperemia with latanoprost, that the commercially available prostaglandin analogs differ significantly with regard to side effects.

  • 2.
    Alm, Albert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Grunden, John W.
    Kwok, Kenneth K.
    Five-year, Multicenter Safety Study of Fixed-combination Latanoprost/Timolol (Xalacom) for Open-angle Glaucoma and Ocular Hypertension2011In: Journal of glaucoma, ISSN 1057-0829, E-ISSN 1536-481X, Vol. 20, no 4, p. 215-222Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate the safety of fixed-combination latanoprost/timolol (Xalacom) in patients requiring additional intraocular pressure (IOP) reduction over 5 years. Methods: This phase 3b, open-label, multicenter study included prostaglandin-naive participants with open-angle glaucoma or ocular hypertension insufficiently responsive to beta-blockers and requiring additional IOP reduction. Participants were evaluated at eleven 6-month visits. A masked assessor evaluated iris/eyelash changes at baseline and 12, 36, and 60 months. Increased iris pigmentation incidence was compared with a historic control from a similarly designed study evaluating latanoprost. Ocular and systemic adverse events were recorded. Results: Among 828/974 treated participants with assessable iris photographs, 233 (28.1%) developed increased iris pigmentation versus 127/380 (33.4%) in the historic controls. Participants with mixed eye colors exhibited greater susceptibility to overall increased iris pigmentation (85.8% in both studies). In this study, most participants (80.3%) with increased iris pigmentation developed only a weak increase. Eyelash changes were seen in 58.1% of participants and darkening of the eyelids in 5-6%; 14.1% experienced a serious adverse event. Adverse events resulted in treatment withdrawal in 133 (13.7%) participants. Most were nonserious ocular adverse events, about half of them ocular irritation. Only 3 of 13 serious systemic adverse events were considered to be drug related by the investigator. Mean IOP reductions were stable over 5 years. Conclusions: After 5 years, more than 70% of participants treated with fixed-combination latanoprost/timolol had no increased iris pigmentation. The fixed combination is safe and well tolerated for long-term treatment in patients with open-angle glaucoma or ocular hypertension.

  • 3.
    Aurell, Sandra
    et al.
    Vastmanland Cty Hosp, AT Ctr, S-72189 Vasteras, Sweden..
    Granstam, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology. Vastmanland Cty Hosp, Dept Ophthalmol, Vasteras, Sweden..
    Bacterial keratitis in a Swedish county hospital: management and clinical outcome2016In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 94, no 3, p. E248-E249Article in journal (Refereed)
  • 4.
    Austeng, Dordi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Blennow, Mats
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Fellman, Vineta
    Fritz, Thomas
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hellström, Ann
    Holmgren, Per Ake
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Jakobsson, Peter
    Jeppsson, Annika
    Johansson, Kent
    Kallen, Karin
    Lagercrantz, Hugo
    Laurini, Ricardo
    Lindberg, Eva
    Lundqvist, Anita
    Marsal, Karel
    Nilstun, Tore
    Nordén Lindeberg, Solveig
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Norman, Mikael
    Olhager, Elisabeth
    Oestlund, Ingrid
    Serenius, Fredrik
    Simic, Marija
    Sjörs, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Stigson, Lennart
    Stjernqvist, Karin
    Strömberg, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Tornqvist, Kristina
    Wennergren, Margareta
    Wallin, Agneta
    Westgren, Magnus
    Incidence of and risk factors for neonatal morbidity after active perinatal care: extremely preterm infants study in Sweden (EXPRESS)2010In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 99, no 7, p. 978-992Article in journal (Refereed)
    Abstract [en]

    Aims: The aim of this study was to determine the incidence of neonatal morbidity in extremely preterm infants and to identify associated risk factors. Methods: Population based study of infants born before 27 gestational weeks and admitted for neonatal intensive care in Sweden during 2004-2007. Results: Of 638 admitted infants, 141 died. Among these, life support was withdrawn in 55 infants because of anticipation of poor long-term outcome. Of 497 surviving infants, 10% developed severe intraventricular haemorrhage (IVH), 5.7% cystic periventricular leucomalacia (cPVL), 41% septicaemia and 5.8% necrotizing enterocolitis (NEC); 61% had patent ductus arteriosus (PDA) and 34% developed retinopathy of prematurity (ROP) stage >= 3. Eighty-five per cent needed mechanical ventilation and 25% developed severe bronchopulmonary dysplasia (BPD). Forty-seven per cent survived to one year of age without any severe IVH, cPVL, severe ROP, severe BPD or NEC. Tocolysis increased and prolonged mechanical ventilation decreased the chances of survival without these morbidities. Maternal smoking and higher gestational duration were associated with lower risk of severe ROP, whereas PDA and poor growth increased this risk. Conclusion: Half of the infants surviving extremely preterm birth suffered from severe neonatal morbidities. Studies on how to reduce these morbidities and on the long-term health of survivors are warranted.

  • 5.
    Austeng, Dordi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Källen, Karin
    Hellström, Ann
    Jakobsson, Peter
    Lundgren, Pia
    Tornqvist, Kristina
    Wallin, Agneta
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Regional differences in screening for retinopathy of prematurity in infants born before 27 weeks' gestation in Sweden: the EXPRESS study2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 4, p. 311-315Article in journal (Refereed)
    Abstract [en]

    Purpose:  The primary aim was to analyse regional incidences of retinopathy of prematurity (ROP) and frequencies of treatment and their relation to perinatal risk factors during a 3-year period. A secondary aim was to study adherence to the study screening protocol in the different regions.

    Methods:  A population-based study of neonatal morbidity in extremely preterm infants in Sweden (EXPRESS) was performed during 2004–2007. Screening for ROP was to start at postnatal age 5 weeks and to continue weekly until the retina was completely vascularized or until regression of ROP. Logistic regression analyses were used for evaluation of differences in incidence of Any ROP, ROP 3 or more and ROP Type 1 between the seven regions of the country.

    Results:  The regional incidence of ROP varied between 54% and 92% for Any ROP, between 25% and 43% for ROP stage 3 or more and between 8% and 23% of infants with ROP Type 1, all of whom were treated. There was no significant difference between the regions regarding ROP Type 1, even when adjusting for known risk factors for ROP.

    Conclusion:  The heterogeneity between the regions regarding the incidence of ROP was reduced with increasing severity of ROP, and there was no heterogeneity regarding frequency of treatment for ROP, which is the most important issue for the children. We cannot exclude observer bias regarding mild ROP and ROP stage 3 in this study.

  • 6.
    Austeng, Dordi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Källén, Karin B. M.
    Hellström, Ann
    Jakobsson, Peter G.
    Johansson, Kent
    Tornqvist, Kristina
    Wallin, Agneta
    Holmström, Gerd E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Screening for Retinopathy of Prematurity in Infants Born Before 27 Weeks' Gestation in Sweden2011In: Archives of ophthalmology (1960), ISSN 0003-9950, Vol. 129, no 2, p. 167-172Article in journal (Refereed)
    Abstract [en]

    Objective: To analyze screening for retinopathy of prematurity (ROP) during a 3-year period in a national cohort of infants born before 27 weeks' gestation. Methods: A national prospective study of neonatal morbidity in extremely preterm infants was performed in Sweden between April 1, 2004, and March 31, 2007. Screening for ROP was to start in the fifth postnatal week and to continue weekly until complete vascularization of the retina or until regression of ROP. Results: The first eye examination was performed no later than the sixth postnatal week in 84.8% of 506 infants, and the last examination was performed at postmenstrual age (PMA) of 38 weeks or later in 96.2% of infants. The mean and median numbers of days between examinations in the total cohort were 8.6 and 7.9 days, respectively (range, 1-27.8 days), and the mean and me-dian numbers of examinations were 12 and 10, respectively. Most infants were treated during a limited period (eg, at PMA of 39 weeks, 75.0% of infants had been treated). Conclusions: The objective of screening for ROP is timely detection of ROP before reaching treatment of criteria, ie, type 1 ROP, according to the Early Treatment for ROP recommendations. In our population of infants born before 27 weeks' gestation, the first examination could safely be postponed until PMA of 31 weeks because the onset of ROP stage 3 did not occur before then and criteria for treatment were not reached before PMA of 32 weeks. Gestational age at birth and PMA at the time of examination should be considered when deciding when and where the next examination should be performed.

  • 7.
    Berggren, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Linnés vittberesta lärjunge seglade med kapten Cook2013In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 110, no 3, p. 103-105Article in journal (Refereed)
  • 8.
    Bjärnhall, Gunilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Tomic, Lidija
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Mishima, Hiromu
    Tsukamoto, Hidetoshi
    Alm, Albert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Retinal mean transit time in patients with primary open-angle glaucoma and normal-tension glaucoma2007In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 85, no 1, p. 67-72Article in journal (Refereed)
    Abstract [en]

    Purpose: To compare the mean transit time (MTT) of retinal circulation in eyes with primary open-angle glaucoma (POAG) and eyes with normal-tension glaucoma (NTG) and examine the possible relationship between MTT and visual field damage, expressed as mean deviation (MD).

    Methods: Video fluorescein angiography was performed in 40 patients with POAG or NTG. Dye curves for fluorescein passing through the retinal arteries and veins were used to calculate MTT in each patient with a computer-assisted technique based on an impulse-response analysis (MTTir).

    Results: We were able to analyse MTTir in all 40 angiograms. Mean (SD) MTTir was 5.0 (1.5) seconds in eyes with POAG and 4.7 (1.4) seconds in eyes with NTG. The difference was not statistically significant. There was a weak but significant correlation between the MD and MTTir (MTTir = 4.12–0.08*MD; r = −0.49, p = 0.0013).

    Conslusions: The results demonstrate that loss of neuronal tissue in glaucoma is combined with an effect on the retinal circulation and that the effect is similar in eyes with NTG and eyes with POAG.

  • 9. Blennow, Mats
    et al.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Fellman, Vineta
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Källén, Karin
    Lagercrantz, Hugo
    Marsál, Karel
    Dept of Obstetrics and Gynecology, Lund University, Lund, Sweden.
    Norden-Lindeberg, Solveig
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Norman, Mikael
    Serenius, Fredrik
    Westgren, Magnus
    Wennergren, Margareta
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Strömberg, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    One-year survival of extremely preterm infants after active perinatal care in Sweden: The EXPRESS Group Members2009In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 301, no 21, p. 2225-2233Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Up-to-date information on infant survival after extremely preterm birth is needed for assessing perinatal care services, clinical guidelines, and parental counseling. OBJECTIVE: To determine the 1-year survival in all infants born before 27 gestational weeks in Sweden during 2004-2007. DESIGN, SETTING, AND PATIENTS: Population-based prospective observational study of extremely preterm infants (707 live-born and 304 stillbirths) born to 887 mothers in 904 deliveries (102 multiple births) in all obstetric and neonatal units in Sweden from April 1, 2004, to March 31, 2007. MAIN OUTCOME MEASURES: Infant survival to 365 days and survival without major neonatal morbidity (intraventricular hemorrhage grade >2, retinopathy of prematurity stage >2, periventricular leukomalacia, necrotizing enterocolitis, severe bronchopulmonary dysplasia). Associations between perinatal interventions and survival. RESULTS: The incidence of extreme prematurity was 3.3 per 1000 infants. Overall perinatal mortality was 45% (from 93% at 22 weeks to 24% at 26 weeks), with 30% stillbirths, including 6.5% intrapartum deaths. Of live-born infants, 91% were admitted to neonatal intensive care and 70% survived to 1 year of age (95% confidence interval [CI], 67%-73%). The Kaplan-Meier survival estimates for 22, 23, 24, 25, and 26 weeks were 9.8% (95% CI, 4%-23%), 53% (95% CI, 44%-63%), 67% (95% CI, 59%-75%), 82% (95% CI, 76%-87%), and 85% (95% CI, 81%-90%), respectively. Lower risk of infant death was associated with tocolytic treatment (adjusted for gestational age odds ratio [OR], 0.43; 95% CI, 0.36-0.52), antenatal corticosteroids (OR, 0.44; 95% CI, 0.24-0.81), surfactant treatment within 2 hours after birth (OR, 0.47; 95% CI, 0.32-0.71), and birth at a level III hospital (OR, 0.49; 95% CI, 0.32-0.75). Among 1-year survivors, 45% had no major neonatal morbidity. CONCLUSION: During 2004 to 2007, 1-year survival of infants born alive at 22 to 26 weeks of gestation in Sweden was 70% and ranged from 9.8% at 22 weeks to 85% at 26 weeks.

  • 10.
    Bodén, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Persson, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Larsson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Striatal Phosphodiesterase 10A and Thinning of the medial Prefrontal Cortex in Schizophrenia - a PET and MRI study2016In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, p. S48-S49Article in journal (Refereed)
  • 11. Bonamy, Anna-Karin E.
    et al.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Stephansson, Olof
    Ludvigsson, Jonas F.
    Cnattingius, Sven
    Preterm Birth and Later Retinal Detachment2013In: Ophthalmology (Rochester, Minn.), ISSN 0161-6420, E-ISSN 1549-4713, Vol. 120, no 11, p. 2278-2285Article in journal (Refereed)
    Abstract [en]

    Objective: Ophthalmologic complications after preterm birth are common. Small studies show an association between retinopathy of prematurity and later retinal detachment. There are no population-based studies of preterm birth and risk of retinal detachment, which was the objective of the current investigation.

    Design: Nationwide Swedish cohort study based on population registries.

    Participants: Of 3 423 697 subjects born in Sweden, 1 271 725 were born between 1973 and 1986 (i.e., before the national screening program for retinopathy of prematurity started), and 2 151 972 were born between 1987 and 2008. The participants were followed up from 1 year of age until 2009.

    Methods: Unadjusted and adjusted hazard ratios (HRs) for retinal detachment were calculated using Cox proportional hazards regression.

    Main Outcome Measures: Incident retinal detachment, as defined by a diagnosis in the Swedish Patient Register (both inpatient and hospital-based outpatient data).

    Results: During follow-up (median follow-up, 17.4 years), 1749 subjects were diagnosed with retinal detachment. Among the 188 852 subjects born prematurely (i.e., at < 37 weeks of gestation), there were 124 cases of retinal detachment, of which 42 occurred in the 20 470 subjects born before 32 weeks of gestation. Compared with subjects born at term (37-41 weeks), the adjusted HR for retinal detachment after extremely preterm birth (< 28 weeks of gestation) was 19.2 (95% confidence interval [CI], 10.3-35.8) for births between 1973 and 1986 and 8.95 (95% CI, 3.98-20.1) for births between 1987 and 2008. The corresponding HRs in subjects born very prematurely (28-31 weeks) were 4.32 (95% CI, 2.70-6.90) and 2.80 (95% CI, 1.38-5.69), respectively. Moderately preterm birth (32-36 weeks) was not associated with an increased risk of retinal detachment.

    Conclusions: Birth before 32 weeks of gestation is associated with a substantially increased relative risk of retinal detachment. These findings may have implications for ophthalmologic follow-up of children and adults born very prematurely. 

  • 12.
    Botling Taube, Amelie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Molecular and epidemiological studies on eyes with pseudoexfoliation syndrome2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Pseudoexfoliation (PEX) syndrome is an age-related condition characterized by the production and accumulation of extracellular fibrillary material in the anterior segment of the eye. PEX predisposes for several pathological conditions, such as glaucoma and complications during and after cataract surgery. The pathogenesis of PEX is not yet fully understood. It is multifactorial with genetics and ageing as contributing factors.

    We aimed to study the proteome in aqueous humor (AH) in PEX in order to increase the knowledge about its pathophysiology. Therefore, we developed sampling techniques and evaluated separation methods necessary for analyzing small sample volumes. Other objectives were to study the lens capsule in eyes with PEX regarding small molecules, and to investigate the association between PEX and cataract surgery in a population-based 30-year follow-up study.

    Samples of AH from eyes with PEX and control eyes were collected during cataract surgery. In pooled, and individual samples, various liquid based separation techniques and high resolution mass spectrometry were utilized. For quantitation, various methods for labeling, and label free techniques were applied. Lens capsules were collected from some of the patients, and analysed by imaging mass spectrometry. A cohort of 1,471 elderly individuals underwent a comprehensive ophthalmological examination at baseline. Medical information was obtained by questionnaires, and from medical records. Incident cases of cataract surgery were identified by review of medical records.

    In the initial study, several techniques were explored for protein detection, and a number of proteins were identified as differentially expressed. In the individually labelled samples, changes in the proteome were observed. Eyes with PEX contained higher levels of proteins involved in inflammation, oxidative stress, and coagulation, suggesting that these mechanisms are involved in the pathogenesis in PEX. The levels of β/γ-crystallins were significantly increased in PEX, which is a novel finding. In the lens capsules from individuals with PEX, changes in the lipid composition was observed with time-of-flight secondary ion mass spectrometry. These changes remain to be elucidated. By multivariate analysis, lens opacities were the first, and PEX the second most important predictor for cataract surgery, the later accounting for a 2.38-fold increased risk for cataract surgery.

    List of papers
    1. Protein content in aqueous humor from patients with pseudoexfoliation (PEX) investigated by capillary-LC MALDI-TOF/TOF MS
    Open this publication in new window or tab >>Protein content in aqueous humor from patients with pseudoexfoliation (PEX) investigated by capillary-LC MALDI-TOF/TOF MS
    Show others...
    2009 (English)In: PROTEOMICS - Clinical Applications, ISSN 1862-8346, E-ISSN 1862-8354, Vol. 3, no 3, p. 299-306Article in journal (Refereed) Published
    Abstract [en]

    Analysis of proteins in human body fluids is challenging since the composition of the sample often is rather complex. Here we present a method for analysis of proteins in aqueous humor from two groups of cataract patients, with and without pseudoexfoliation (PEX). Aqueous humor is an extracellular fluid contained in the anterior chamber of the eye between the cornea and iris. The limited volume of sample requires sophisticated analysis techniques. Our method is based on a total tryptic digestion of the sample followed by capillary LC-MALDI MS and MS/MS analysis of the peptides. The method is rapid, efficient and suitable as a complement or alternative to more commonly used methods based on gel electrophoretic experiments. With this method we found and unambiguously identified 30 nonredundant proteins. Proteins found include general transport proteins such as albumin and apolipoprotein A1 but also specific proteins involved in immune response, such as   complement factors. Cystatin C, clusterin, and crystallins were also found. Although the number of proteins was roughly the same in both groups there was a significant difference in their identities. These findings may give some new insights into the pathophysiology of the PEX syndrome.

    Keywords
    Aqueous humor, Capillary liquid chromatography, Human body fluids, MALDI-TOF MS/MS, Pseudoexfoliation syndrome
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-97814 (URN)10.1002/prca.200780077 (DOI)000264794700002 ()
    Available from: 2008-11-20 Created: 2008-11-20 Last updated: 2017-12-14Bibliographically approved
    2. Proteins in aqueous humor from cataract patients with and without pseudoexfoliation syndrome
    Open this publication in new window or tab >>Proteins in aqueous humor from cataract patients with and without pseudoexfoliation syndrome
    Show others...
    2012 (English)In: European journal of mass spectrometry, ISSN 1469-0667, E-ISSN 1751-6838, Vol. 18, no 6, p. 531-541Article in journal (Refereed) Published
    Abstract [en]

    The aim of this study was to investigate the protein content in aqueous humor in eyes with and without pseudoexfoliations (PEX) and to evaluate the quantitative proteomics method, isobaric tagging for relative and absolute protein quantification (iTRAQ), in combination with two separation methods followed by matrix-assisted Laser desorption/ionization (MALDI) mass spectrometry and tandem mass spectrometry (MS/MS). During cataract surgery, samples of aqueous humor were collected from 20 eyes with PEX and from 18 control eyes. The relative concentrations of proteins in the pooled samples of ten PEX eyes and eight controls were evaluated after trypsin digestion and labeling of the peptides with (iTRAQ) reagent. Two separation methods, Liquid chromatography (LC) and capillary electrophoresis (CE) were used, followed by MALDI mass spectrometry and MS/MS. Furthermore, 1D gel electrophoresis was performed on the remaining ten pooled PEX samples and ten control samples. The gel material was separated by nano-liquid chromatography (nano-LC) followed by Linear-ion-trap quadrupole Fourier transformation ion cyclotron resonance (FT-ICR). Fifty four proteins were identified in the LC runs and 24 with CE. The relative concentrations of beta-crystallines B2 and S were raised and those of angiotensinogen and osteopontin lowered in the PEX sample compared to the control. The trends regarding beta-crystallines B2, angiotensinogen and osteopontin were confirmed by the 1D gel electrophoresis.

    Keywords
    pseudoexfoliations (PEX), isobaric tagging, protein quantification, proteomics, aqueous humour, osteopontin, angiotensinogen
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-197670 (URN)10.1255/ejms.1208 (DOI)000315745600007 ()
    Available from: 2013-04-02 Created: 2013-04-02 Last updated: 2017-12-06Bibliographically approved
    3. Proteomic Analysis of the Aqueous Humor in Eyes with Pseudoexfoliation Syndrome
    Open this publication in new window or tab >>Proteomic Analysis of the Aqueous Humor in Eyes with Pseudoexfoliation Syndrome
    (English)Article in journal (Refereed) Submitted
    Keywords
    Aqueous humor; Pseudoexfoliation syndrome; Quantitative proteomics; Dimethyl labelling; Mass spectrometry
    National Category
    Ophthalmology Analytical Chemistry
    Research subject
    Ophtalmology
    Identifiers
    urn:nbn:se:uu:diva-260949 (URN)
    Available from: 2015-08-26 Created: 2015-08-26 Last updated: 2015-10-01
    4. Imaging of Human Lens Capsules with Pseudoexfoliation Syndrome by Time of Flight Secondary Ion Mass Spectrometry (TOF-SIMS)
    Open this publication in new window or tab >>Imaging of Human Lens Capsules with Pseudoexfoliation Syndrome by Time of Flight Secondary Ion Mass Spectrometry (TOF-SIMS)
    (English)Manuscript (preprint) (Other academic)
    Keywords
    PEX, cataract, lens capsule, time of flight secondary mass spectrometry (TOF-SIMS), imaging mass spectrometry (IMS), sphingolipids
    National Category
    Ophthalmology
    Research subject
    Ophtalmology; Chemistry with specialization in Analytical Chemistry
    Identifiers
    urn:nbn:se:uu:diva-260946 (URN)
    Funder
    Swedish Research Council, 621-2011-4423
    Available from: 2015-08-26 Created: 2015-08-26 Last updated: 2015-10-01
    5. Pseudoexfoliation and cataract surgery: a population-based 30-year follow-up study
    Open this publication in new window or tab >>Pseudoexfoliation and cataract surgery: a population-based 30-year follow-up study
    2015 (English)In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 93, no 8, p. 774-777Article in journal (Refereed) Published
    Abstract [en]

    PURPOSE:

    To study the relationship between pseudoexfoliation (PEX) and cataract surgery in a population in which PEX is a common finding.

    METHODS:

    Survival analyses were performed in a cohort of 760 residents 65-74 years of age, examined in a population survey in the municipality of Tierp, Sweden, during 1984-1986. To expand the cohort, participants in other studies in Tierp were enrolled. Additionally, subjects were recruited by means of glaucoma case records established at the Eye Department in Tierp in 1978-2007. In total, the cohort comprised 1471 individuals, representing more than 15 900 person-years of risk. Information on cataract surgery was obtained from the glaucoma case records and from medical records.

    RESULTS:

    By the end of the study in August 2014, 564 subjects had undergone cataract surgery. Of these cases, 224 were affected by PEX at baseline. In multivariate analyses, PEX was the second most important predictor for cataract surgery after lens opacities, accounting for a 2.38-fold (95% confidence interval 2.01-2.84) increased risk.

    CONCLUSION:

    The results strongly suggest that PEX is a predictor for cataract surgery in the population under study.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2015
    Keywords
    cataract, cataract surgery, epidemiology, exfoliation syndrome, pseudoexfoliation, risk factor
    National Category
    Ophthalmology
    Research subject
    Ophtalmology
    Identifiers
    urn:nbn:se:uu:diva-260948 (URN)10.1111/aos12789 (DOI)000367654500034 ()
    Available from: 2015-08-26 Created: 2015-08-26 Last updated: 2017-12-04Bibliographically approved
  • 13.
    Botling Taube, Amelie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Konzer, Anne
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Alm, Albert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Proteomic Analysis of the Aqueous Humor in Eyes with Pseudoexfoliation SyndromeArticle in journal (Refereed)
  • 14.
    Botling Taube, Amelie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Mi, Jia
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Alm, Albert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Imaging of Human Lens Capsules with Pseudoexfoliation Syndrome by Time of Flight Secondary Ion Mass Spectrometry (TOF-SIMS)Manuscript (preprint) (Other academic)
  • 15. Breitbart, Eberhardt
    et al.
    Cesarini, Jean-Pierre
    de Gruijl, Frank
    Hietanen, Marja
    Mariutti, G
    Mc Kinley, Alister
    Okuno,
    Roy, C
    Schulmeister, Karl
    Sliney, David
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Stuck, Bruce
    Swerdlow, Anthony
    Van Deventer, E
    Zeeb, H
    Protecting workers from ultraviolet radiation2007Book (Other academic)
  • 16.
    Brodd, Katarina Strand
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Grönqvist, Helena
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Strömberg, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Grönqvist, Erik
    Uppsala University, Units outside the University, Office of Labour Market Policy Evaluation.
    von Hofsten, Claes
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Rosander, Kerstin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Development of smooth pursuit eye movements in very preterm infants: 1. General aspects2011In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 100, no 7, p. 983-991Article in journal (Refereed)
    Abstract [en]

    Aim:  To investigate early oculo-motor development in a population-based cohort of very preterm infants.

    Methods:  Early oculo-motor development was prospectively studied by measuring smooth pursuit eye movements at 2 and 4 months corrected age in a population of very preterm infants born in Uppsala County 2004–2007. Eighty-one preterm infants were studied, and 32 healthy term infants constituted the control group.

    Results:  The study group consisted of infants with a mean gestational age of28 + 5 weeks. At 2 and 4 months corrected age, infants born very preterm showed lower gain (p < 0.001) and proportion of smooth pursuit eyemovements (p < 0.001) compared to the control group. The boys showed higher gain of smooth pursuit eye movements at both 2 and 4 months corrected age, compared to girls.

    Conclusions:  Oculo-motor development measured by smooth pursuit eye movements is delayed in very preterm infants at 2 and 4 months corrected age. This might be a risk factor or early indicator of later perceptual and behavioural impairment.

  • 17.
    Brodd, Katarina Strand
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Grönqvist, Helena
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Grönqvist, Erik
    Uppsala University, Units outside the University, Office of Labour Market Policy Evaluation.
    Rosander, Kerstin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Development of Smooth Pursuit Eye Movements in very preterm born infants: 3. Association to perinatal risk factors2012In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 101, no 2, p. 164-171Article in journal (Refereed)
    Abstract [en]

    Aim:  To investigate the association between perinatal risk factors and neonatal complications and early oculo-motor development in very preterm infants.

    Methods:  Perinatal risk factors were identified, and the potential association with early oculo-motor development was evaluated by measuring smooth pursuit eye movements (SP) at 2 and 4 months' corrected age (CA) in a population of very preterm infants born in Uppsala County 2004-2007 (n = 113).

    Results:  Among the 15 tested factors, eight showed significant association in univariate analysis with lower levels of SP at 4 months' CA, namely administration of prenatal corticosteroids, gestational age, birthweight, bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, intraventricular haemorrhage >grade 2, and persistent ductus arteriosus. At 2 months' CA, only retinopathy of prematurity >stage 2 was associated with lower levels of SP. When all factors significant in the univariate tests were included in multiple regressions aimed to assess each factor's independent relation to SP, periventricular leukomalacia was the only significant independent factor. When adding 2-5 of the significant factors using multiple regression analysis, the levels of SP became lower.

    Conclusion:  Perinatal risk factors were associated with lower levels of SP. This could be interpreted as delayed or disturbed development of normal oculomotor ability.

  • 18. Bucht, Curry
    et al.
    Söderberg, Per G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Manneberg, Göran
    Fully automated corneal endothelial morphometry of images captured by clinical specular microscopy2010In: Ophthalmic Technologies XX / [ed] Fabrice Manns, Per G. Söderberg, Arthur Ho, San Francisco, CA: SPIE , 2010, p. 1E-1-1E-8Conference paper (Refereed)
  • 19. Bucht, Curry
    et al.
    Söderberg, Per G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Manneberg, Göran
    Fully automated corneal endothelial morphometry of images captured by clinical specular microscopy2009In: Ophthalmic Technologies XIX / [ed] Fabrice Manns; Per G. Söderberg; Arthur Ho, San José, CA: SPIE , 2009, Vol. 7163, p. 15:1-15:8Conference paper (Refereed)
  • 20.
    Bucht, Curry
    et al.
    S:t Eriks Ögonsjukhus, Inst. f. Neurovetenskap, KI.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Manneberg, Göran
    Biomedicinsk fysik och röntgenfysik, Inst. för tillämpad fysik.
    Simulation of specular microscopy images of corneal endothelium, a tool for control of measurement errors2011In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 89, no 3, p. e242-e250Article in journal (Refereed)
    Abstract [en]

    Purpose: We aimed at developing simulation software capable of producing images of corneal endothelium close to identical to images captured by clinical specular microscopy with defined morphometrical characteristics. It was further planned to demonstrate the usefulness of the simulator by analysing measurement errors associated with a trained operator using a commercially available semi-automatic algorithm for analysis of simulated images.

    Methods: Software was developed that allows creation of unique images of the corneal endothelium expressing morphology close to identical with that seen in images of corneal specular microscopy. Several hundred unique images of the corneal endothelium were generated with randomization, spanning a physiological range of endothelial cell density. As an example of the usefulness of the simulator for analysis of measurement errors in corneal specular microscopy, a total of 12 of all the images generated were randomly selected such that the endothelial cell density expressed was evenly distributed over the physiological range of endothelial cell density. The images were transferred to a personal computer. The imagenet-640 software was used to analyse endothelial cell size variation, percentage of hexagonal endothelial cells, and endothelial cell density.

    Results: The simulator developed allows randomized generation of corneal specular microscopy images with a preset expected average and variation of cell structure. Calculated morphometric information of each cell is stored in the simulator. The image quality can secondarily be varied with a toolbox of filters to approximate a large spectrum of clinically captured images. As an example of the use of the simulator, measurement errors associated with one trained operator using the imagenet-640 software, and focusing on endothelial cell density, were examined. The functional dependence between morphometric information estimated with the imagenet-640 software algorithm and real morphometric information as provided by the simulator was analysed with regression. It was demonstrated that that the estimations of endothelial cell size variation was associated with a scaling error and that the random error was strongly dependent on the operator.

    Conclusion: The newly developed simulator for randomized generation of morphometrically defined corneal specular microscopy images for the first time makes it possible to estimate a spatial scaling error of an available semi-automatic algorithm and to determine the random measurement error of important morphometric estimates in a defined reference sample of images. It is anticipated that the simulator will be a valuable tool for the generation of a large set of morphometrically well-characterized corneal specular microscopy images that can be used for calibration among research centres, for minimization of random errors and for measurement of quality control. Simulated images will be useful for the development of fully automatic analysis of corneal endothelial cell morphometry.

  • 21.
    Caines, Elizabeth
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Dahl, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Longterm oculomotor and visual function in spina bifida cystica: a population-based study2007In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 85, no 6, p. 662-666Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To document and describe the development from birth of visual and oculomotor functions in a group of children with spina bifida cystica (myelomeningocele and myeloschisis [MMC]). The emphasis in this study is on findings at 12-14 year follow-up. METHODS: Twenty children aged 12-14 years with myelomeningocele and Chiari-related malformations were examined by an orthoptist and a paediatric ophthalmologist. A further child who did not wish to participate actively in the study is also reported. Visual acuity for near and distance, refractometer readings in cycloplegia, the presence of ocular motility disorders and nystagmus were recorded. Accommodation, convergence, colour vision and stereo acuity were assessed and the fundus and media were examined. RESULTS: Six children (29%) in the study group had subnormal vision, although no child was visually impaired. Eleven (52%) showed manifest strabismus and 17 (81%) had a significant refractive error. Near visual acuity was normal in nearly all the children, but accommodation was defective in 10. Nine children had nystagmus and two had optic atrophy. No visual field defects were found. CONCLUSIONS: The high incidence of ocular disturbances in children with spina bifida highlights the importance of regular ophthalmological investigation and follow-up.

  • 22. Dong, Xiuqin
    et al.
    Löfgren, Stefan
    Ayala, Marcelo
    Söderberg, Per G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Maximum tolerable dose for avoidance of cataract induced by ultraviolet radiation-B for 18 to 60 week old rats2005In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 80, no 4, p. 561-566Article in journal (Refereed)
    Abstract [en]

    The purpose of the present study was to investigate the maximum tolerable dose for avoidance of UVR-B-induced cataract in rats in the age interval 18-60 weeks and establish the functional relationship between age and sensitivity to UVR-B. Four groups of 20 albino Sprague-Dawley rats each, aged 18, 26, 40 or 60 weeks, were included. Each age group was divided into five UVR dose sub-groups. The rats were unilaterally exposed to ultraviolet radiation (lambda(max)=302.6 nm, lambda0.5=4.5 nm). The incident dose on the cornea varied between 0 and 9.2 kJ m(-2). One week after exposure, the rats were sacrificed and both lenses were extracted. The intensity of forward light scattering was measured and photographs were taken. The functional relationship between age and sensitivity to UVR-B was estimated as the maximum tolerable dose based on rats age from 3 to 60 weeks. The maximum tolerable dose for 18, 26, 40, and 60 weeks, respectively, was estimated to 5.2, 4.9, 4.7, and 5.1 kJ m(-2). The sensitivity to UVR-B for Sprague-Dawley rats increases with increasing age during the first third of the rat life span, and then stabilizes to a constant level during the remaining two-thirds.

  • 23. Dong, Xiuqin
    et al.
    Söderberg, Per G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Ayala, Marcelo
    Löfgren, Stefan
    The effect of exposure time on maximum acceptable dose for avoidance of ultraviolet radiation-induced cataract2005In: Ophthalmic Research, ISSN 0030-3747, E-ISSN 1423-0259, Vol. 37, no 4, p. 197-201Article in journal (Refereed)
    Abstract [en]

    The effect of exposure time on maximum acceptable dose (MAD) for avoidance of ultraviolet radiation B (UVRB)-induced cataract was investigated. Sprague-Dawley rats were divided into 5 exposure time groups: 7.5, 15, 30, 60, and 120 min. Each exposure time group was divided into 5 dose subgroups: 0, 1, 2, 4, and 8 kJ/m2. The rats were unilaterally exposed to UVR around 300 nm. One week after the exposure, macroscopic structure was recorded and lens forward light scattering was measured. MAD for avoidance of UVRB-induced cataract was estimated based on the dose-response function. MAD for avoidance of UVRB-induced cataract for 7.5, 15, 30, 60, and 120 min exposures was estimated to be 2.0, 1.4, 1.9, 1.8 and 2.2 kJ/m2, respectively. In the exposure time domain 7.5-120 min, MAD for avoidance of UVRB-induced cataract depends on exposure time.

  • 24.
    Ekström, Curt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Incidence of open-angle glaucoma in central Sweden2008In: Acta ophthalmologica, ISSN 1755-375X, Vol. 86, no 7, p. 747-754Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To estimate the incidence rate of open-angle glaucoma (OAG) in a population in which pseudoexfoliation is a common finding. METHODS: A population-based survey of 760 people aged 65-74 years was conducted in the municipality of Tierp, in central Sweden, during 1984-86. Visual fields (VFs) were tested with the Competer 350 automated perimeter. The present report concerns 711 people, all of whom participated in the survey and were not diagnosed with glaucoma. Since 1988, a follow-up study of the 530 individuals in this cohort with normal and reliable VFs has been in progress. Incident cases of OAG were identified among study participants and patients seeking medical attention at the Eye Department in Tierp. Records of prescriptions for anti-glaucoma drugs were used to search for unidentified patients. A time-weighted mean intraocular pressure (IOP) for all visits was calculated. RESULTS: By the end of the study in May 2006, 51 new cases of definite OAG had been identified, 31 with capsular and 20 with chronic simple glaucoma. Of these, 46 cases were detected in the follow-up study, corresponding to an incidence of 7.11 (95% confidence interval 5.06-9.17) per 1000 person-years. Twelve of the 51 cases were classified as normal-tension glaucoma, all of which were found in the follow-up study. Open-angle glaucoma with a mean IOP > or = 23 mmHg tended to emerge closer to the baseline examination than OAG with a mean IOP < 23 mmHg. CONCLUSIONS: The incidence of OAG was high compared with that reported for other studies conducted in White populations.

  • 25.
    Ekström, Curt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Risk factors for incident open-angle glaucoma: a population-based 20-year follow-up study2012In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 90, no 4, p. 316-321Article in journal (Refereed)
    Abstract [en]

    Purpose: To study the effect of potential risk factors on the development of open-angle glaucoma (OAG) in a population in which pseudoexfoliation (PEX) is a common finding.

    Methods: In 1984-1986, a population-based survey of 760 people aged 65-74 years was conducted in the municipality of Tierp, Sweden. From 1988 to 2006, a follow-up study of the 530 people with normal visual fields has been in progress. To increase the cohort, 273 ophthalmic outpatients were enroled. Reliable visual fields were available for 679 people, representing 6 126 person-years at risk. A time-weighted mean intraocular pressure (IOP) for all visits was calculated.

    Results: Sixty-four subjects developed definite OAG, 29 of whom were exposed to PEX. Risk factors associated with OAG were higher age, a positive family history, increased IOP and PEX. The age-standardized rate ratio (SRR) was 14.8 times (95% confidence interval [CI] 7.92-27.8) greater in subjects with mean IOP >/=20 mmHg than in those with mean IOP /=20 mmHg.

    Conclusion: Increased IOP and PEX were serious risk factors for incident OAG. The effect of PEX was mediated by increased IOP.

  • 26.
    Ekström, Curt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Alm, Albert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Pseudoexfoliation as a risk factor for prevalent open-angle glaucoma2008In: Acta ophthalmologica, ISSN 1755-375X, Vol. 86, no 7, p. 741-746Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To estimate the risk of open-angle glaucoma (OAG) associated with exposure to pseudoexfoliation (PEX) and increased intraocular pressure (IOP). METHODS: In 1984-86, a cross-sectional, population-based survey was conducted in the municipality of Tierp, central Sweden. Its target population comprised 2429 residents aged 65-74 years. In addition to a sample of 760 people, patients previously diagnosed with glaucoma were examined. The prevalence of OAG in the target population was estimated from the prevalence in the sample and patients already diagnosed. A review of prevalent cases in 1984-86 was undertaken in 2006. RESULTS: Definite OAG was established in 77 cases, corresponding to a prevalence of 5.3% (95% confidence interval [CI] 4.4-6.2). Of these, 23 represented newly detected cases. The prevalence of PEX was 17.2% (95% CI 14.6-19.9), calculated from 134 cases in the population sample. When adjusting for gender, PEX was associated with a 4.7-fold (95% CI 2.2-9.4) increased risk of OAG. For clinical cases only, the risk was 16-fold (95% CI 4.8-56) greater in subjects with PEX, compared with those without PEX. In individuals without a previous diagnosis of glaucoma, an IOP > or = 20 mmHg was associated with a 9.7-fold (95% CI 3.7-27) increased risk, but PEX alone was not a risk factor for OAG (adjusted odds ratio = 0.96). CONCLUSIONS: Pseudoexfoliation was associated with OAG only in people previously diagnosed with the disease. In cases detected in the population-based survey, increased IOP was a serious risk factor.

  • 27.
    Ekström, Curt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Botling Taube, Amelie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Pseudoexfoliation and cataract surgery: a population-based 30-year follow-up study2015In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 93, no 8, p. 774-777Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    To study the relationship between pseudoexfoliation (PEX) and cataract surgery in a population in which PEX is a common finding.

    METHODS:

    Survival analyses were performed in a cohort of 760 residents 65-74 years of age, examined in a population survey in the municipality of Tierp, Sweden, during 1984-1986. To expand the cohort, participants in other studies in Tierp were enrolled. Additionally, subjects were recruited by means of glaucoma case records established at the Eye Department in Tierp in 1978-2007. In total, the cohort comprised 1471 individuals, representing more than 15 900 person-years of risk. Information on cataract surgery was obtained from the glaucoma case records and from medical records.

    RESULTS:

    By the end of the study in August 2014, 564 subjects had undergone cataract surgery. Of these cases, 224 were affected by PEX at baseline. In multivariate analyses, PEX was the second most important predictor for cataract surgery after lens opacities, accounting for a 2.38-fold (95% confidence interval 2.01-2.84) increased risk.

    CONCLUSION:

    The results strongly suggest that PEX is a predictor for cataract surgery in the population under study.

  • 28.
    Ekström, Curt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Open-angle glaucoma and Alzheimer´s disease: a population-based 30 year follow-up study2016In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 95, no 2, p. E157-E158Article in journal (Other academic)
  • 29.
    Ekström, Curt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Pseudoexfoliation and Alzheimer´s disease: a population-based 30-year follow-up study2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 4, p. 355-358Article in journal (Refereed)
  • 30.
    Engström, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Thuomas, Karl Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Naeser, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Stålberg, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Jonsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Facial nerve enhancement in Bell's palsy demonstrated by different gadolinium-enhanced magnetic resonance imaging techniques.1993In: Archives of Otolaryngology - Head & Neck Surgery, ISSN 0886-4470, E-ISSN 1538-361X, Vol. 119, no 2, p. 221-225Article in journal (Refereed)
    Abstract [en]

    Twenty-one patients with an acute complete peripheral facial palsy, Bell's palsy, were examined by medium- and high-Tesla magnetic resonance imaging. Three contrast techniques were used: intravenous gadolinium; oral carbohydrate and intravenous gadolinium; and gadolinium, carbohydrate, and readministration of gadolinium. Three to 22 days after the onset of palsy, 12 of the 21 patients demonstrated ipsilateral facial nerve enhancement, most consistently in the meatal region, which is indicative of an inflammatory reaction. Two to 4.5 months after the onset, the enhancement had disappeared in 10 of the 12 patients. For the individual patient, contrast-enhanced magnetic resonance imaging gave little or no help in predicting the outcome of palsy. It is speculated that the intake of carbohydrate and readministration of gadolinium may improve the sensitivity of medium-high-Tesla magnetic resonance imaging in some cases.

  • 31.
    Eriksson, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Aspects of Optical Coherence Tomography (OCT) in Healthy Eyes and Eyes with Retinal Diseases2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Optical coherence tomography (OCT) is a technique in which cross-sectional images from intraocular tissue can be obtained. The quantitative and qualitative examinations are used for evaluating retinal diseases. Conventional OCT (Stratus) is mainly used, but the new Spectral domain (Cirrus) OCT, which has improved technology, may provide more reliable measurements.

    The aim of the study was to collect normal values of macular thickness in children and adults and to evaluate the effect of age and/or gender, to compare measurement variability in healthy eyes and eyes with age-related macular degeneration (AMD), to compare Stratus and Cirrus OCT and to study the effect of cataract surgery on macula.

    Sixty-seven healthy adults and 56 children, 30 patients with AMD, 34 patients with diabetes and cataract and 35 healthy controls were included. The quantitative maps in Stratus and Cirrus were used and manual correction of foveal location was evaluated. Qualitative OCT was compared to fluorescein angiography (FA) after cataract surgery.

    The mean values of macular thickness in Stratus OCT were 207µm in adults and 204 µm in children. The measurement variability was low. Macular thickness decreased with age in adults, but not in children. No correlation with gender was found. In eyes with wet AMD, there were small differences in measurement variability comparing Stratus and Cirrus OCT. After manual correction in Cirrus OCT, the coefficients of repeatability were improved to values close to the repeatability in normal eyes. Two thirds of the diabetic and half of the control eyes showed leakage on FA after cataract surgery. Qualitative OCT corresponded poorly to FA in diabetic eyes. A thicker macula, assessed with OCT, was often observed without any obvious effect on visual acuity.  OCT was as good as FA in revealing clinically relevant changes in macula after surgery, and was the technique recommended for follow-up.

    List of papers
    1. Repeatability in and interchangeability between the macular and the fast macular thickness map protocols: a study on normal eyes with Stratus optical coherence tomography
    Open this publication in new window or tab >>Repeatability in and interchangeability between the macular and the fast macular thickness map protocols: a study on normal eyes with Stratus optical coherence tomography
    2009 (English)In: Acta ophthalmologica, ISSN 1755-3768, Vol. 87, no 7, p. 725-730Article in journal (Refereed) Published
    Abstract [en]

    Purpose: To collect a normal material and to compare the macular and the fast macular thickness map protocols regarding normal values and repeatability. Methods: Sixty-seven individuals underwent three repeated scans with the macular thickness protocol; 45 of them also had three scans with the fast thickness protocol in Stratus optical coherence tomography (OCT). The maps were divided into nine ETDRS fields, where thickness values were presented. The repeatability was calculated as intraclass correlation coefficient (ICC), coefficient of variance (CV) and coefficient of repeatability (CR). For comparison between the two protocols, limits of agreement were determined according to Bland-Altman. Results: Normal values for the two protocols were very close. Repeatability was high. ICC for all areas was 0.92-0.98. CV was less than 1% and CR was 6-8 mum for both protocols, with the exception of the fovea in the fast protocol (where CV was 1.44% and CR 12.4 mum). Limits of agreement between the two protocols were less than 10 mum as a rule. Conclusion: Normal values for the protocols are equal and they both have excellent repeatability. The fast macular map is a good alternative with the possible exception of the fovea, where variation is twice that of the macular thickness map.

    Keywords
    macular thickness maps, normal values, optical coherence tomography, repeatability
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-104911 (URN)10.1111/j.1755-3768.2008.01345.x (DOI)000270999300006 ()18937816 (PubMedID)
    Available from: 2009-05-30 Created: 2009-05-30 Last updated: 2010-09-23Bibliographically approved
    2. A population-based study of macular thickness in full-term children assessed with Stratus OCT: normative data and repeatability.
    Open this publication in new window or tab >>A population-based study of macular thickness in full-term children assessed with Stratus OCT: normative data and repeatability.
    2009 (English)In: Acta ophthalmologica, ISSN 1755-3768, Vol. 87, no 7, p. 741-745Article in journal (Refereed) Published
    Abstract [en]

    Purpose: We aimed to determine normal macular thickness values, assessed with optical coherence tomography (OCT), in a population of full-term children of normal birthweight. Methods: A total of 56 children, aged 5-16 years, randomly chosen from the population register, were examined with Stratus OCT. Only children with visual acuity < 0.2 logMAR, spherical equivalent of - 3 to + 3 D and astigmatism < 2 D were included. The fast macular map protocol was used and three examinations were performed in each eye. One eye was then randomized for further analyses. Mean values for the nine ETDRS areas, foveal minimum thickness and macular volume were calculated for 55 eyes. Coefficients of variance and intraclass correlations were calculated for each area. Results: All children co-operated well and no child was excluded for lack of concentration. Mean +/- standard deviation central macular thickness was 204 +/- 19 mum. Mean total macular volume was 7.11 +/- 0.35 mm(3). No correlations were found between age, gender and macular thickness. Coefficients of variance were < 2% and intraclass correlations were > 0.9 in all areas, except the foveal minimum. Conclusions: Normal values for macular thickness in healthy full-term children were reported. As the Stratus OCT provides normal values only for adults, these data are a better alternative for comparison with children with retinal abnormalities. We concluded that OCT is suitable for examining the retina in children aged 5-16 years and has the same high level of repeatability as in adults.

    Keywords
    children, full-term, macular thickness, optical coherence tomography (OCT), repeatability
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-104400 (URN)10.1111/j.1755-3768.2008.01357.x (DOI)000270999300009 ()18811639 (PubMedID)
    Available from: 2009-05-30 Created: 2009-05-28 Last updated: 2010-10-04Bibliographically approved
    3. Macular thickness decreases with age in normal eyes: A study on the macular thickness map protocol in the Stratus OCT
    Open this publication in new window or tab >>Macular thickness decreases with age in normal eyes: A study on the macular thickness map protocol in the Stratus OCT
    2008 (English)In: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079, Vol. 93, no 11, p. 1148-1452Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND/AIM: Retinal and retinal nerve fibre layer (RNFL) thinning with age have been described in histological studies. In vivo techniques like optical coherence tomography (OCT), has shown thinning of optic nerve RNFL and the retina in specific areas. One would expect thinning of the total macula, but so far, a correlation with the quantitative OCT macular map tool and age has not been found. METHODS: Sixty-seven healthy individuals underwent three repeated scans in both eyes with the macular thickness map protocol in the Stratus OCT. That protocol divides the macula area in nine ETDRS fields.The RNFL was measured in one specific location close to the optic disc. Correlations between retinal, RNFL thickness, macular volume and age were determined. RESULTS: We found a statistically significant negative relationship between retinal thickness and age for all ETDRS areas, total macular volume and RNFL thickness. Retinal thickness decreased with 0,26-0,46 microm, the macula volume 0,01 mm(3) and RNFL with 0,09 microm per year. CONCLUSION: Retinal thickness within the area covered by the macular map significantly decreases with age. In the area examined in the papillomacular bundle, 20% of the retinal thinning is due to the RNFL and 80% due to thinning of other layers of the retina.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-104910 (URN)10.1136/bjo.2007.131094 (DOI)000271091900009 ()19019921 (PubMedID)
    Available from: 2009-05-30 Created: 2009-05-30 Last updated: 2017-12-13Bibliographically approved
    4. Is quantitative spectral-domain superior to time-domain optical coherence tomography (OCT) in eyes with age-related macular degeneration?
    Open this publication in new window or tab >>Is quantitative spectral-domain superior to time-domain optical coherence tomography (OCT) in eyes with age-related macular degeneration?
    2012 (English)In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 90, no 7, p. 620-627Article in journal (Refereed) Published
    Abstract [en]

    Purpose: The aim of this study was to determine the variability of macular map measurements, for two generations of optical coherence tomography (OCT) instruments, in eyes with wet age related macular degeneration (AMD) and low visual acuity. Methods: Patients were examined with Stratus OCT and Cirrus HD-OCT. The macular thickness was assessed with the 'macular thickness map scan' and 'fast protocol' in Stratus and with the 512 × 128 and 200 × 200 cube protocols in Cirrus OCT. Two measurements were taken one directly after the other, at the first visit to analyse repeatability. Approximately 1 week later, a third measurement was taken to analyse reproducibility. In Cirrus OCT, a manual correction of foveal location was also performed. Repeatability and reproducibility were calculated as a coefficient of variance (CoV) and a coefficient of repeatability/reproducibility. Results: Repeatability for central macular thickness (expressed as CoV) was about three per cent for all protocols, and the coefficient of repeatability between 34 and 54 μm. Reproducibility (also expressed as CoV) was between four to seven per cent and coefficient of repeatability between 64 and 89 μm. After manual adjustment of foveal location in Cirrus OCT, the coefficient of repeatability improved to 12-18 μm, and the coefficient of reproducibility to 44-47 μm. Conclusions: In eyes affected by wet AMD, there were small differences in repeatability and reproducibility when comparing quantitative maps in Stratus and Cirrus OCT. However, when the software for manual correction of foveal position in Cirrus OCT was used, the variability decreased markedly, and the repeatability was close to what had been reported in normal eyes, demonstrating a significant, potential advantage of spectral-domain over time-domain OCT.

    Keywords
    age-related macular degeneration, quantitative optical coherence tomography, repeatability, reproducibility
    National Category
    Ophthalmology
    Research subject
    Ophtalmology
    Identifiers
    urn:nbn:se:uu:diva-184945 (URN)10.1111/j.1755-3768.2011.02112.x (DOI)000310548500017 ()
    Available from: 2012-11-19 Created: 2012-11-15 Last updated: 2017-12-07Bibliographically approved
    5. Macular edema and visual outcome following cataract surgery in patients with diabetic retinopathy and controls
    Open this publication in new window or tab >>Macular edema and visual outcome following cataract surgery in patients with diabetic retinopathy and controls
    Show others...
    2011 (English)In: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 249, no 3, p. 349-359Article in journal (Refereed) Published
    Abstract [en]

    Cystoid macular edema (CME) is a well-known complication after cataract surgery, and diabetic retinopathy is reported to be an important risk factor for impaired visual recovery. In this prospective study, we compared visual outcome 6 months after surgery in eyes with moderate retinopathy and no previous ME with a control group, and observed the incidence of ME seen on fluorescein angiography (FA) and optical coherence tomography (OCT).

    Thirty-four patients with type-2 diabetes and 35 controls were enrolled. Best-corrected visual acuity (VA) letters ETDRS was measured pre-op, at day 7, week 6 and month 6. FA performed pre-op and at week 6 was divided into three leakage patterns. OCT performed pre-op, at week 6 and month 6 was qualitatively divided into three types. Macular thickness was measured in three circular fields (central subfield, inner and outer circle) from the macular maps.

    There was no statistically significant difference in VA before surgery, at day 7 or at 6 months, but at 6 weeks there was a significant difference with lower VA in the diabetic group. Six percent of control and 12% of diabetic eyes developed a clinical CME defined as a loss of > 5 letters between day 7 and week 6. Incidence of FA leakage was 23% in control and 76% in diabetic eyes. At 6 weeks, 20% of control and 44% of the diabetic eyes had qualitative changes on OCT. A statistically significant increase in thickness was observed for all three macular areas in both groups, part of it remaining at 6 months. There were, however, no differences in central macular thickness between the groups at any visit. Retinal thickening had poor correlation with VA.

    The final visual outcome in eyes with mild to moderate retinopathy, without previous ME, is as good as in normal eyes, but an increased frequency of macular changes may protract recovery of full vision. Changes on OCT or FA are often seen without any obvious effect on VA. OCT is as good as FA at detecting a clinical CME, and is the technique recommended for follow-up before FA is considered.

    Keywords
    Visual outcome, Phacoemulsification, Cystoid macular edema, Optical coherence tomography, Fluorescein angiography, Sub-clinical macular thickening
    National Category
    Medical and Health Sciences
    Research subject
    Ophtalmology
    Identifiers
    urn:nbn:se:uu:diva-128901 (URN)10.1007/s00417-010-1484-9 (DOI)000288454200003 ()20827486 (PubMedID)
    Available from: 2010-08-03 Created: 2010-08-02 Last updated: 2018-05-28Bibliographically approved
  • 32.
    Eriksson, Urban
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Alm, Albert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Macular thickness decreases with age in normal eyes: A study on the macular thickness map protocol in the Stratus OCT2008In: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079, Vol. 93, no 11, p. 1148-1452Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIM: Retinal and retinal nerve fibre layer (RNFL) thinning with age have been described in histological studies. In vivo techniques like optical coherence tomography (OCT), has shown thinning of optic nerve RNFL and the retina in specific areas. One would expect thinning of the total macula, but so far, a correlation with the quantitative OCT macular map tool and age has not been found. METHODS: Sixty-seven healthy individuals underwent three repeated scans in both eyes with the macular thickness map protocol in the Stratus OCT. That protocol divides the macula area in nine ETDRS fields.The RNFL was measured in one specific location close to the optic disc. Correlations between retinal, RNFL thickness, macular volume and age were determined. RESULTS: We found a statistically significant negative relationship between retinal thickness and age for all ETDRS areas, total macular volume and RNFL thickness. Retinal thickness decreased with 0,26-0,46 microm, the macula volume 0,01 mm(3) and RNFL with 0,09 microm per year. CONCLUSION: Retinal thickness within the area covered by the macular map significantly decreases with age. In the area examined in the papillomacular bundle, 20% of the retinal thinning is due to the RNFL and 80% due to thinning of other layers of the retina.

  • 33.
    Eriksson, Urban
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Alm, Albert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Repeatability in and interchangeability between the macular and the fast macular thickness map protocols: a study on normal eyes with Stratus optical coherence tomography2009In: Acta ophthalmologica, ISSN 1755-3768, Vol. 87, no 7, p. 725-730Article in journal (Refereed)
    Abstract [en]

    Purpose: To collect a normal material and to compare the macular and the fast macular thickness map protocols regarding normal values and repeatability. Methods: Sixty-seven individuals underwent three repeated scans with the macular thickness protocol; 45 of them also had three scans with the fast thickness protocol in Stratus optical coherence tomography (OCT). The maps were divided into nine ETDRS fields, where thickness values were presented. The repeatability was calculated as intraclass correlation coefficient (ICC), coefficient of variance (CV) and coefficient of repeatability (CR). For comparison between the two protocols, limits of agreement were determined according to Bland-Altman. Results: Normal values for the two protocols were very close. Repeatability was high. ICC for all areas was 0.92-0.98. CV was less than 1% and CR was 6-8 mum for both protocols, with the exception of the fovea in the fast protocol (where CV was 1.44% and CR 12.4 mum). Limits of agreement between the two protocols were less than 10 mum as a rule. Conclusion: Normal values for the protocols are equal and they both have excellent repeatability. The fast macular map is a good alternative with the possible exception of the fovea, where variation is twice that of the macular thickness map.

  • 34.
    Eriksson, Urban
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Alm, Albert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Bjärnhall, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Granstam, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Wikberg Matsson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Macular edema and visual outcome following cataract surgery in patients with diabetic retinopathy and controls2011In: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 249, no 3, p. 349-359Article in journal (Refereed)
    Abstract [en]

    Cystoid macular edema (CME) is a well-known complication after cataract surgery, and diabetic retinopathy is reported to be an important risk factor for impaired visual recovery. In this prospective study, we compared visual outcome 6 months after surgery in eyes with moderate retinopathy and no previous ME with a control group, and observed the incidence of ME seen on fluorescein angiography (FA) and optical coherence tomography (OCT).

    Thirty-four patients with type-2 diabetes and 35 controls were enrolled. Best-corrected visual acuity (VA) letters ETDRS was measured pre-op, at day 7, week 6 and month 6. FA performed pre-op and at week 6 was divided into three leakage patterns. OCT performed pre-op, at week 6 and month 6 was qualitatively divided into three types. Macular thickness was measured in three circular fields (central subfield, inner and outer circle) from the macular maps.

    There was no statistically significant difference in VA before surgery, at day 7 or at 6 months, but at 6 weeks there was a significant difference with lower VA in the diabetic group. Six percent of control and 12% of diabetic eyes developed a clinical CME defined as a loss of > 5 letters between day 7 and week 6. Incidence of FA leakage was 23% in control and 76% in diabetic eyes. At 6 weeks, 20% of control and 44% of the diabetic eyes had qualitative changes on OCT. A statistically significant increase in thickness was observed for all three macular areas in both groups, part of it remaining at 6 months. There were, however, no differences in central macular thickness between the groups at any visit. Retinal thickening had poor correlation with VA.

    The final visual outcome in eyes with mild to moderate retinopathy, without previous ME, is as good as in normal eyes, but an increased frequency of macular changes may protract recovery of full vision. Changes on OCT or FA are often seen without any obvious effect on VA. OCT is as good as FA at detecting a clinical CME, and is the technique recommended for follow-up before FA is considered.

  • 35.
    Eriksson, Urban
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Alm, Albert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Larsson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Is quantitative spectral-domain superior to time-domain optical coherence tomography (OCT) in eyes with age-related macular degeneration?2012In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 90, no 7, p. 620-627Article in journal (Refereed)
    Abstract [en]

    Purpose: The aim of this study was to determine the variability of macular map measurements, for two generations of optical coherence tomography (OCT) instruments, in eyes with wet age related macular degeneration (AMD) and low visual acuity. Methods: Patients were examined with Stratus OCT and Cirrus HD-OCT. The macular thickness was assessed with the 'macular thickness map scan' and 'fast protocol' in Stratus and with the 512 × 128 and 200 × 200 cube protocols in Cirrus OCT. Two measurements were taken one directly after the other, at the first visit to analyse repeatability. Approximately 1 week later, a third measurement was taken to analyse reproducibility. In Cirrus OCT, a manual correction of foveal location was also performed. Repeatability and reproducibility were calculated as a coefficient of variance (CoV) and a coefficient of repeatability/reproducibility. Results: Repeatability for central macular thickness (expressed as CoV) was about three per cent for all protocols, and the coefficient of repeatability between 34 and 54 μm. Reproducibility (also expressed as CoV) was between four to seven per cent and coefficient of repeatability between 64 and 89 μm. After manual adjustment of foveal location in Cirrus OCT, the coefficient of repeatability improved to 12-18 μm, and the coefficient of reproducibility to 44-47 μm. Conclusions: In eyes affected by wet AMD, there were small differences in repeatability and reproducibility when comparing quantitative maps in Stratus and Cirrus OCT. However, when the software for manual correction of foveal position in Cirrus OCT was used, the variability decreased markedly, and the repeatability was close to what had been reported in normal eyes, demonstrating a significant, potential advantage of spectral-domain over time-domain OCT.

  • 36.
    Eriksson, Urban
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Alm, Albert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Larsson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    A population-based study of macular thickness in full-term children assessed with Stratus OCT: normative data and repeatability.2009In: Acta ophthalmologica, ISSN 1755-3768, Vol. 87, no 7, p. 741-745Article in journal (Refereed)
    Abstract [en]

    Purpose: We aimed to determine normal macular thickness values, assessed with optical coherence tomography (OCT), in a population of full-term children of normal birthweight. Methods: A total of 56 children, aged 5-16 years, randomly chosen from the population register, were examined with Stratus OCT. Only children with visual acuity < 0.2 logMAR, spherical equivalent of - 3 to + 3 D and astigmatism < 2 D were included. The fast macular map protocol was used and three examinations were performed in each eye. One eye was then randomized for further analyses. Mean values for the nine ETDRS areas, foveal minimum thickness and macular volume were calculated for 55 eyes. Coefficients of variance and intraclass correlations were calculated for each area. Results: All children co-operated well and no child was excluded for lack of concentration. Mean +/- standard deviation central macular thickness was 204 +/- 19 mum. Mean total macular volume was 7.11 +/- 0.35 mm(3). No correlations were found between age, gender and macular thickness. Coefficients of variance were < 2% and intraclass correlations were > 0.9 in all areas, except the foveal minimum. Conclusions: Normal values for macular thickness in healthy full-term children were reported. As the Stratus OCT provides normal values only for adults, these data are a better alternative for comparison with children with retinal abnormalities. We concluded that OCT is suitable for examining the retina in children aged 5-16 years and has the same high level of repeatability as in adults.

  • 37. Fahnehjelm, Kristina Teär
    et al.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Ying, Liu
    Haglind, Charlotte Bieneck
    Nordenström, Anna
    Halldin, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Alm, Jan
    Nemeth, Antal
    von Döbeln, Ulrika
    Ocular characteristics in 10 children with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: a cross-sectional study with long-term follow-up.2008In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 86, no 3, p. 329-337Article in journal (Refereed)
    Abstract [en]

    PURPOSE

    To present long-term ocular complications and electroretinographic (ERG) findings in children with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency - a life-threatening metabolic disease - and the relation to age at diagnosis, treatment and other clinical parameters.

    METHODS

    Ten children with LCHAD deficiency underwent repeated ophthalmological evaluations including ERG.

    RESULTS

    All 10 children developed chorioretinal pathology. Regardless of age at diagnosis, initiation of treatment and age at examination, inter-individual differences were present. Profound chorioretinal atrophy, severe visual impairment and progressive myopia had developed in two teenagers. Milder chorioretinopathy with or without subnormal visual acuity was present in all other children. ERG was pathological in seven children. The chorioretinopathy often started in the peripapillary or perimacular areas. In one patient, unilateral visual impairment was associated with fibrosis.

    CONCLUSION

    Early diagnosis and adequate therapy might delay but not prevent the progression of retinal complications. Late diagnosis with severe symptoms at diagnosis, neonatal hypoglycaemia and frequent decompensations may increase the progression rate of the chorioretinopathy. LCHAD deficiency, a potentially lethal disease, is sometimes difficult to diagnose. Unusual chorioretinal findings should alert the ophthalmologist to the long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, especially if there is a history of neonatal hypoglycaemia or failure to thrive.

  • 38.
    Feresiadou, Amalia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Eriksson, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Larsen, Hans-Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nygren, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Melberg, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Recurrence of Susac Syndrome following 23 Years of Remission2014In: Case Reports in Neurology, ISSN 1662-680X, E-ISSN 1662-680X, Vol. 6, no 2, p. 171-175Article in journal (Refereed)
    Abstract [en]

    Susac syndrome is an autoimmune microangiopathy affecting the brain, retina and inner ear (cochlea and semicircular canals), leading to encephalopathy, branch retinal artery occlusions (BRAOs) and asymmetric neurosensory hearing loss, respectively. The natural history and long-term prognosis are variable as the disease has been shown to be monophasic and self-limiting, polycyclic or chronic continuous. We describe a 35-year-old woman who presented with a sudden hearing loss in the left ear in the 37th week of her second pregnancy. She subsequently developed BRAO in the right eye 2.5 months after having given birth. MRI findings included round lesions in the corpus callosum which are pathognomonic for Susac syndrome. Previous patient records documented encephalopathy, sudden deafness of the right ear and visual field defects in the left eye at the age of 12, followed by permanent hearing and visual defects. We expand on the variability in the course of Susac syndrome as recurrence may occur after as long as 23 years. Cases of monophasic self-limiting Susac syndrome may in fact turn polycyclic with an interval of more than 2 decades between the bouts of the disease. In these cases, suspecting the development of exacerbation early is important in order to start the treatment promptly.

  • 39.
    Frisk, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Mandahl, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Lönnerholm, Gudmar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Cataracts after autologous bone marrow transplantation in children2000In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 89, no 7, p. 814-819Article in journal (Refereed)
    Abstract [en]

    We recorded the incidence and degree of posterior subcapsular cataract (PSC) in 29 children who had undergone autologous (n = 28) or syngeneic (n = 1) bone marrow transplantation (BMT) due to haematologic or lymphoid malignancy. Conditioning prior to transplantation consisted either of a combination of chemotherapy and total body irradiation (TBI) (n = 21) or of chemotherapy only (n = 8). TBI was given in one fraction of 7.5 Gy. Nine patients had received previous cranial irradiation. The patients were followed for 4-10 y (median 8y) after transplantation. Of 29 patients, 22 developed PSC, all within 4 y after BMT. With the exception of one patient who developed unilateral PSC, all had received TBI. Conversely, 100% of those who received TBI developed PSC. In this group (+TBI), eight patients (38%) developed significant PSC, defined as best corrected visual acuity < 0.8 in either eye. Six patients (10 eyes) have since needed surgical repair consisting of extracapsular cataract extraction and intraocular lens implantation. There was no clear relationship between previous cranial irradiation and cataract development, nor any other obvious baseline differences between those in the +TBI group who developed significant PSC and those who did not. Although effects of previous therapy cannot be ruled out, TBI appears to be the main cause of PSC in this group of patients. Twelve patients in the +TBI group had well-preserved visual acuity throughout the study, reflecting a slow progression of PSC. This compares favourably with previous reports of allogeneic BMT, possibly owing to less need for corticosteroids after autologous BMT.

    We conclude that the incidence of PSC was high after autologous BMT where the conditioning regimen included total body irradiation.

  • 40.
    Galichanin, Konstantin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Exposure to subthreshold dose of UVR-B induces apoptosis in the lens epithelial cells and does not in the lens cortical fibre cells2017In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 95, no 8, p. 834-838Article in journal (Refereed)
    Abstract [en]

    Purpose: The aim of this study was to investigate in which part of the lens invivo exposure to subthreshold dose of UVR-B radiation induces apoptosis.

    Methods: Twenty 6-week-old female albino Sprague-Dawley rats were exposed to subthreshold dose (1kJ/m(2)) of UVR-B unilaterally and killed at 120hr after exposure. Lenses were enucleated and dissected on three regions: the lens epithelium, the cortex and the nucleus. The lens nucleus then was removed. Apoptosis markers p53 and caspase 3 were used to study apoptosis in the lens regions. qRT-PCR and Western blot were utilized to analyse the lenses.

    Results: TP53 and CASP3 mRNA expressions are increased in exposed lenses, both in the lens epithelium and in the cortex regions, in relation to non-exposed lenses. Expression of p53 protein is increased in exposed lens epithelium in relation to non-exposed lens epithelium. Caspase 3 protein is expressed in exposed lens epithelial cells, while it is not expressed in non-exposed lens epithelial cells. p53 and caspase 3 proteins are not expressed in either exposed nor non-exposed lens fibre cells.

    Conclusion: Exposure to UVR-B increases mRNA transcription of apoptosis marker p53 invivo in both regions of the lens and of apoptosis marker caspase 3 in the lens cortex. Exposure to UVR-B increases p53 and caspase 3 proteins expression just in the lens epithelium. In vivo exposure to subthreshold dose of UVR-B induces apoptosis in the lens epithelial cells and does not in the lens fibre cells.

  • 41.
    Galichanin, Konstantin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Löfgren, Stefan
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Cataract after repeated daily in vivo exposure to ultraviolet radiation2014In: Health Physics, ISSN 0017-9078, E-ISSN 1538-5159, Vol. 107, no 6, p. 523-529Article in journal (Refereed)
    Abstract [en]

    Epidemiological data indicate a correlation between lifelong exposure to ultraviolet radiation and cortical cataract. However, there is no quantitative experimental data on the effect of daily repeated in vivo exposures of the eye to UVR. Therefore, this experiment was designed to verify whether the dose additivity for UVR exposures holds through periods of time up to 30 d. Eighty rats were conditioned to a rat restrainer 5 d prior to exposure. All animals were divided into four exposure period groups of 1, 3, 10, and 30 d of exposure to UVR. Each exposure period group of 20 animals was randomly divided into five cumulated UVR dose subgroups. Eighteen-wk-old non-anesthetized albino Sprague-Dawley rats were exposed daily to UVR-300 nm for 15 min. One week after the last exposure, animals were sacrificed. The lenses were extracted for macroscopic imaging of dark-field anatomy, and degree of cataract was quantified by measurement of the intensity of forward lens light scattering. Maximum tolerable dose (MTD2.3:16), a statistically defined standard for sensitivity for the threshold for UVR cataract, was estimated for each exposure period. Exposed lenses developed cataract with varying appearance on the anterior surface. Single low doses of UVR accumulated to cause cataract during periods up to 30 d. MTD2.3:16 for 1, 3, 10, and 30 d of repeated exposures was estimated to 4.70, 4.74, 4.80, and 6.00 kJ m, respectively. In conclusion, the lens sensitivity to UVR-B for 18-wk-old Sprague-Dawley rats decreases with the increasing number of days being exposed. 

  • 42.
    Galichanin, Konstantin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Svedlund, Jessica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Kinetics of GADD45a, TP53 and CASP3 gene expression in the rat lens in vivo in response to exposure to double threshold dose of UV-B radiation2012In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 97, no 1, p. 19-23Article in journal (Refereed)
    Abstract [en]

    The purpose of the present study was to investigate the evolution of expression of mRNA message for the genes for the genome stress sensor GADD45α, the apoptosis initiator TP53 and the apoptosis executor CASP3 in the rat lens in vivo in response to exposure to UVR around 300 nm. Forty six week old female albino Sprague-Dawley rats were unilaterally exposed to double threshold dose for cataract induction, 8 kJ/m2 (8.9 W/m2 for 15 min), of UVR (λmax = 300 nm). The animals were sacrificed at 1, 5, 24 and 120 h following exposure to UVR-B. For each of the GADD45α, TP53 and CASP3 genes, respectively, mRNA expression in the lenses was measured by quantitative RT-PCR. It was found that expression of mRNA for GADD45α transiently increases between 5 and 24 h after exposure. TP53 is slightly downregulated in exposed lenses at 1 and 5 h after exposure and thereafter the mRNA expression increases with a constant rate of 9.4∗10−3 rel. units/h to a 1.8 fold increase at 120 h after exposure. Expression of mRNA for CASP3 is downregulated at 1, 5 and 24 h after in vivo exposure and then increases with a constant rate of 4.7∗10−3 rel. units/h, upto a 1.3 fold upregulation at 120 h. Double threshold dose of UVR, for short delay onset of cataract, in vivo causes a transient upregulation of the stress sensor GADD45α, a concurrent downregulation of TP53 and CASP3, followed by a constant upregulation of TP53 that precedes a constant upregulation of CASP3.

  • 43.
    Galichanin, Konstantin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology. Karolinska Inst, St Eriks Eye Hosp, S-10401 Stockholm, Sweden.
    Talebizadeh, Nooshin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Characterization of Molecular Mechanisms of In vivo UVR Induced Cataract2012In: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, no 69, article id e4016Article in journal (Refereed)
    Abstract [en]

    Cataract is the leading cause of blindness in the world (1). The World Health Organization defines cataract as a clouding of the lens of the eye which impedes the transfer of light. Cataract is a multi-factorial disease associated with diabetes, smoking, ultraviolet radiation (UVR), alcohol, ionizing radiation, steroids and hypertension. There is strong experimental (2-4) and epidemiological evidence (5,6) that UVR causes cataract. We developed an animal model for UVR B induced cataract in both anesthetized (7) and non-anesthetized animals (8). The only cure for cataract is surgery but this treatment is not accessible to all. It has been estimated that a delay of onset of cataract for 10 years could reduce the need for cataract surgery by 50% (9). To delay the incidence of cataract, it is needed to understand the mechanisms of cataract formation and find effective prevention strategies. Among the mechanisms for cataract development, apoptosis plays a crucial role in initiation of cataract in humans and animals (10). Our focus has recently been apoptosis in the lens as the mechanism for cataract development (8,11,12). It is anticipated that a better understanding of the effect of UVR on the apoptosis pathway will provide possibilities for discovery of new pharmaceuticals to prevent cataract. In this article, we describe how cataract can be experimentally induced by in vivo exposure to UVR-B. Further RT-PCR and immunohistochemistry are presented as tools to study molecular mechanisms of UVR-B induced cataract.

  • 44.
    Galichanin, Konstantin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Wang, Jing
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Löfgren, Stefan
    Inst. för Klinisk Neurovetenskap, Karolinska Institutet.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    A new universal rat restrainer for ophthalmic research2011In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 89, no 1, p. E67-E71Article in journal (Refereed)
    Abstract [en]

    Purpose: Immobilization of rats is required in many psychological and physiological experiments. The aim of the current paper was to invent a universal device allowing for adaptation of rats of a wide age range and to maximize convenience for in vivo exposure to optical radiation under not-anaesthetized conditions.

    Methods: Eighty-three 6-week-old and three 18-week-old Sprague-Dawley albino female rats were progressively familiarized daily with the restraining device 5 days prior to exposure to acquire a conditioned response and to reduce stress. After initial habituation, 10 min preceding the ultraviolet radiation (UVR) exposure, the animal was fixed in the rat restrainer. Each unanaesthetized animal was unilaterally exposed to a single dose of 8 kJ/m(2) UVR-300 nm for 15 min. Three of the 6-week-old and three of the 18-week-old rats were in vivo exposed to UVR once for 10 consecutive days.

    Results: All rats acclimatized well to immobilization in the restrainer. Young rats adapted quicker than older rats. The device prevented head movement and body rotation, which allowed for uncomplicated single as well as repeated in vivo exposures to UVR.

    Conclusions: The restrainer effectively immobilizes unanaesthetized rats in the age range 6-18 weeks old, making it useful in future projects involving chronic repeated in vivo exposure of the eye to UVR.

  • 45.
    Galichanin, Konstantin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Yu, Zhaohua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Upregulation of GADD45a, TP53 and CASP3 mRNA expression in the rat lens after in vivo exposure to sub-threshold exposure to UVR B2014In: Journal of Ocular Biology, ISSN 2334-2838, Vol. 2, no 1, p. 5-Article in journal (Refereed)
    Abstract [en]

    Purpose:

    The objective of the present study was to investigate the evolution of mRNA expression of the stress sensor GADD45α, the apoptosis initiator TP53 and the apoptosis executor CASP3 in the rat lens after in vivo exposure to sub-threshold dose of UVR-B.

    Methods:

    Forty six-week-old female albino Sprague-Dawley rats were unilaterally exposed to a sub-threshold dose, 1 kJ/m2 (1.1 W/m2 for 15 min), of UVR (λmax = 300 nm). Anesthetized and dilated eyes were exposed to UVB radiation. The animals were sacrificed at 1, 5, 24 and 120 h post-exposure. mRNA expression of the GADD45α, TP53 and CASP3 genes in the lenses was measured by quantitative RT‑PCR, and fold change in mRNA expression between exposed and unexposed lenses was calculated.

    Results:

    mRNA expression for GADD45α increased to a 1.2 fold change at 1 h after exposure and then returned to no change at 120 h. mRNA expression for TP53 increased with a regression coefficient of 0.04 h-1 to a maximum of 1.67 fold change. mRNA expression for CASP3 increased with a regression coefficient of 4.5 x10-3 rel. units/h to a 1.46 fold change at 120 h after exposure.

    Conclusions:

    A sub-threshold in vivo exposure to UVR-B causes a transient upregulation of the stress sensor GADD45α at 1 h after exposure, a saturating upregulation of TP53 and a subsequent constant upregulation of CASP3 in the rat lens.

  • 46.
    Granstam, Sven-Olof
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Granstam, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Endothelin-induced changes in blood flow in STZ-diabetic and non-diabetic rats: relation to nitric oxide synthase and cyclooxygenase inhibition2011In: Journal of Physiological Sciences, ISSN 1880-6546, E-ISSN 1880-6562, Vol. 61, no 6, p. 497-505Article in journal (Refereed)
    Abstract [en]

    In this study, using the microsphere method, the hemodynamic response to endothelin-1 (ET-1) in healthy and streptozotocin (STZ)-diabetic rats was evaluated as well as the influences of inhibition of nitric oxide (NO)-synthase using L-NAME (N omega-nitro-l-arginine methyl ester) and the cyclooxygenase inhibitor indomethacin. Blood flow (Q) was measured in tissues of interest for vascular complications in diabetes such as kidney, eye, brain, heart and skeletal muscle with the main focus on ophthalmic circulation. Under resting conditions, evidence for renal vasoconstriction was found in diabetic animals. In both groups, administration of L-NAME reduced Q in all investigated tissues indicating a basal NO influence. In the normal rats, ET-1 induced a significant increase in blood pressure and intense vasoconstriction in all tissues except in the choroid of the eye and in the brain, where it induced an increased Q. In the STZ-diabetic rats, effects of ET-1 were less pronounced. Pretreatment with L-NAME, but not the cyclooxygenase inhibitor, abolished the ET-1-induced vasodilation in the choroid of both groups. Administration of ET A receptor antagonist BQ-123 reduced the ET-1-induced vasodilation in the choroid only in diabetic animals. In conclusion, evidence for altered vascular endothelial response to ET-1 in STZ-diabetic animals was found particularly in the ophthalmic circulation. The findings suggest differential involvement of receptors in the response to ET-1 in normal and STZ-diabetic animals.

  • 47. Gäddlin, Per-Olof
    et al.
    Finnström, Orvar
    Hellgren, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Leijon, Ingemar
    Hospital readmissions and morbidity in a fifteen-year follow-up of very low birthweight children in Southeast Sweden2007In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 96, no 4, p. 499-505Article in journal (Refereed)
    Abstract [en]

    Aim: To study the effect of very low birthweight on hospital care and morbidity, and their relationship to gender, birthweight and neonatal complications. Methods: Eighty-five very low birthweight (VLBW; <= 1500 g) children and term controls born in 1987-1988 in south-east region of Sweden were checked in registers regarding readmissions and diagnoses, need for habilitation and child psychiatric care up to 15 years of age. Ophthalmological examinations were made at age 4 in 64 of VLBW and 61 of control children, and at age 15 in 59 of VLBW and 55 of control children. Results: VLBW boys had three times more readmissions compared with normal weight control boys (p = 0.003). Neonatal risk factors for readmissions were gestational age under 30 weeks (OR 3.1), birthweight less than 1000 g (OR 4.6), mechanical ventilation (OR 9.5) and more than 60 days' stay in neonatal ward (OR 5.0). A minority of VLBW children had an impairment/handicap such as cerebral palsy (CP) in five (5.9%) children, attention deficit hyperactivity disorders (ADHD) in five children, and blindness due to retinopathy of prematurity in one child. One child in the control group had ADHD. At the 15-year examination median visual acuity in the best eye was better in the control group (1.6) than in the VLBW group (1.3) (p = 0.009). 32% of VLBW children and 11% of controls had latent or manifest strabismus (p = 0.007). Conclusion: Risk factors for readmissions were gender, low gestational age, birthweight < 1000 g or mechanical ventilation. A minority of VLBW children had a handicap that influenced their daily life activities at 15 years of age.

  • 48.
    Hardenborg, Emilia
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Taube, Amelie Botling
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Hanrieder, Jörg
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Andersson, Marit
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Alm, Albert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Protein content in aqueous humor from patients with pseudoexfoliation (PEX) investigated by capillary-LC MALDI-TOF/TOF MS2009In: PROTEOMICS - Clinical Applications, ISSN 1862-8346, E-ISSN 1862-8354, Vol. 3, no 3, p. 299-306Article in journal (Refereed)
    Abstract [en]

    Analysis of proteins in human body fluids is challenging since the composition of the sample often is rather complex. Here we present a method for analysis of proteins in aqueous humor from two groups of cataract patients, with and without pseudoexfoliation (PEX). Aqueous humor is an extracellular fluid contained in the anterior chamber of the eye between the cornea and iris. The limited volume of sample requires sophisticated analysis techniques. Our method is based on a total tryptic digestion of the sample followed by capillary LC-MALDI MS and MS/MS analysis of the peptides. The method is rapid, efficient and suitable as a complement or alternative to more commonly used methods based on gel electrophoretic experiments. With this method we found and unambiguously identified 30 nonredundant proteins. Proteins found include general transport proteins such as albumin and apolipoprotein A1 but also specific proteins involved in immune response, such as   complement factors. Cystatin C, clusterin, and crystallins were also found. Although the number of proteins was roughly the same in both groups there was a significant difference in their identities. These findings may give some new insights into the pathophysiology of the PEX syndrome.

  • 49.
    Hedman, Katarina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Taube, Adam
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Information Science, Statistics.
    Which endpoint: mean intraocular pressure or proportion of successful patients?2003In: Journal of glaucoma, ISSN 1057-0829, E-ISSN 1536-481X, Vol. 12, no 4, p. 321-332Article in journal (Refereed)
    Abstract [en]

    A reduction in intraocular pressure in clinical trials can be determined through the mean intraocular pressure, through the proportion of patients who have the intraocular pressure reduced to a specific target intraocular pressure, or both. Since both these possible endpoints measure the shift of 2 intraocular pressure distributions, we recommend that only one of them be tested. In general, testing the difference between mean-values is much more efficient than testing the difference between proportions. However, proportions of successful patients are valuable in showing the clinical implication of a reduction in mean intraocular pressure, particularly when evaluating a moderate pressure reduction. The effect of a small mean intraocular pressure reduction on the probability to reach the target intraocular pressure is pointed out, particularly the fact that it can be substantial even if the mean reduction is smaller than the measurement error.

  • 50.
    Hedman, Katarina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Watson, Peter
    Alm, Albert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    The Effect of Latanoprost on Intraocular Pressure During 2 Years of Treatment2002In: Survey of ophthalmology, ISSN 0039-6257, E-ISSN 1879-3304, Vol. 47, no S1, p. 65-76Article in journal (Refereed)
    Abstract [en]

    Our objective was to study the intraocular pressure (IOP) in open-angle glaucoma or ocular hypertensive patients during long-term treatment with latanoprost. A total of 532 patients treated with 0.005% latanoprost were enrolled, including 493 and 113 patients treated for 6 and 24 months, respectively. Mean IOP was analyzed with the analysis of variance technique. The risk of treatment failure was analyzed with survival analysis technique. After 2 weeks of latanoprost treatment, the mean IOP was reduced 8.2 (32%) and 8.9 (34%) mm Hg in the subgroups of patients treated for 6 and 24 months, respectively. The change in mean IOP during 2 years of latanoprost treatment was not statistically significant (p = 0.15). Patients with primary open-angle glaucoma or ocular hypertension showed an 86% and 97% chance of receiving a sufficient IOP reduction with latanoprost (p < 0.01), repectively. The initial mean IOP reduction was maintained throughout the 2 years of treatment.

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