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  • 1. Ayala, Marcelo
    et al.
    Strid, Hilja
    Örebro University, School of Health and Medical Sciences.
    Jacobsson, Ulrika
    Söderberg, Per G.
    p53 expression and apoptosis in the lens after ultraviolet radiation exposure2007In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 48, no 9, p. 4187-4191Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To localize p53 protein and active caspase-3 in the albino rat lens and to compare p53 mRNA and active caspase-3 expression in ultraviolet radiation (UVR) 300 nm exposed lenses and their contralateral nonexposed controls. METHODS: Ten Sprague-Dawley albino rats were unilaterally exposed to 8 kJ/m(2) UVR, and the contralateral eyes were left nonexposed. In total, four exposed lenses and their respective contralateral nonexposed lenses were analyzed by immunohistochemistry to localize p53 and active caspase-3. In addition, six exposed and contralateral nonexposed lenses were analyzed by real-time RT-PCR. Quantified p53 and caspase-3 expression were compared between the in vivo UVR 300 nm exposed lenses and the contralateral nonexposed lenses. RESULTS: All lenses exposed to UVR developed cataract. Immunohistochemistry showed that p53 and active caspase-3 were localized in the lens epithelial cells. Quantified p53 and caspase-3 expression were significantly higher in lenses exposed to UVR than in nonexposed lenses. CONCLUSIONS: p53 and caspase-3 expression increase in lens epithelial cells after UVR exposure. In the lens, apoptosis induced by UVR may be associated with increased p53 expression.

  • 2.
    Barth, Henrik
    et al.
    Department of Ophthalmology, Lund University Hospital, Biomedicinskt centrum (BMC), Lund, Sweden.
    Crafoord, Sven
    Örebro University, School of Medical Sciences. Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Andréasson, Sten
    Department of Ophthalmology, Lund University Hospital, Biomedicinskt centrum (BMC), Lund, Sweden.
    Ghosh, Fredrik
    Department of Ophthalmology, Lund University Hospital, Biomedicinskt centrum (BMC), Lund, Sweden.
    A cross-linked hyaluronic acid hydrogel (Healaflow(®)) as a novel vitreous substitute2016In: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 254, no 4, p. 697-703Article in journal (Refereed)
    Abstract [en]

    Purpose: Vitrectomy requires the substitution of the natural vitreous, as well as tamponading of retinal breaks. Clinically available alternatives such as gas and silicone oil have side effects such as inflammation, secondary glaucoma, cataract, and a need for head posturing. In this study, a hydrogel of cross-linked sodium hyaluronic acid (Healaflow(®)) is evaluated for use as a novel vitreous substitute.

    Methods: A combined 25-20-gauge pars plana vitrectomy with posterior vitreous detachment was performed in the right eye of twelve pigmented rabbits, with subsequent injection of approximately 1 ml Healaflow(®). Clinical evaluation, measurement of intraocular pressure (IOP), and full-field ERG were performed postoperatively. The rabbits were sacrificed at different time-points between 42 and 105 days. After enucleation, the eyes were examined macroscopically, photographed, and prepared for histological examination with routine microscopy and immunohistochemistry.

    Results: Healaflow(®) was successfully used with standard surgical procedures and remained translucent but did lose most of its viscosity during the postoperative period. One rabbit was lost due to unrelated causes. In two eyes iatrogenic partial retinal detachments were seen, and in two eyes significant cataract developed due to intra-operative complications. ERG-recordings revealed no toxic effect on rod or cone function. Routine microscopy and immunohistochemistry demonstrated normal morphology with some Müller cell activation (up-regulation of glial acidic fibrillary protein, GFAP) compared to unoperated eyes and no significant DNA-fragmentation (TUNEL-assay).

    Conclusions: Healaflow® did not affect retinal morphology or function negatively during long-term use as a vitreous substitute, making it highly interesting in this setting. An estimated retention time of a few weeks suggests potential for use as a short-term tamponade. Future work will include an increased ratio of cross-linking to prolong the structural integrity of the gel.

  • 3.
    Barth, Henrik
    et al.
    Lund University Hospital, Department of Ophthalmology, Lund, Sweden.
    Crafoord, Sven
    Örebro University, School of Medical Sciences. Department of Ophthalmology.
    Ghosh, Fredrik K.
    Lund University Hospital, Department of Ophthalmology, Lund, Sweden.
    Developing a retinal detachment model for in vivo testing of vitreous substitutes with repeated pars plana vitrectomy2018In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 9, article id 5941Article in journal (Other academic)
  • 4.
    Barth, Henrik
    et al.
    Department of Ophthalmology, Lund University, Lund, Sweden .
    Crafoord, Sven
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    O'Shea, Timothy M.
    Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, USA .
    Pritchard, Christopher D.
    Harvard-Massachusetts Institute of Technology, Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, USA .
    Langer, Robert
    Harvard-Massachusetts Institute of Technology, Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, USA .
    Ghosh, Fredrik
    Department of Ophthalmology, Lund University, Lund, Sweden .
    A new model for in vitro testing of vitreous substitute candidates2014In: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 252, no 10, p. 1581-1592Article in journal (Refereed)
    Abstract [en]

    Purpose: To describe a new model for in vitro assessment of novel vitreous substitute candidates.

    Methods: The biological impact of three vitreous substitute candidates was explored in a retinal explant culture model; a polyalkylimide hydrogel (Bio-Alcamid (R)), a two component hydrogel of 20 wt.% poly (ethylene glycol) in phosphate buffered saline (PEG) and a cross-linked sodium hyaluronic acid hydrogel (Healaflow (R)). The gels where applied to explanted adult rat retinas and then kept in culture for 2, 5 and 10 days. Gel-exposed explants were compared with explants incubated under standard tissue culture conditions. Cryosections of the specimens were stained with hematoxylin and eosin, immunohistochemical markers (GFAP, Vimentin, Neurofilament 160, PKC, Rhodopsin) and TUNEL.

    Results: Explants kept under standard conditions as well as PEG-exposed explants displayed disruption of retinal layers with moderate pyknosis of all neurons. They also displayed moderate labeling of apoptotic cells. Bio-Alcamid (R)-exposed explants displayed severe thinning and disruption of retinal layers with massive cell death. Healaflow (R)-treated explants displayed normal retinal lamination with significantly better preservation of retinal neurons compared with control specimens, and almost no signs of apoptosis. Retinas exposed to Healaflow (R) and retinas kept under standard conditions showed variable labeling of GFAP with generally low expression and some areas of upregulation. PEG-exposed retinas showed increased GFAP labeling and Bio-Alcamid (R)-exposed retinas showed sparse labeling of GFAP.

    Conclusions: Research into novel vitreous substitutes has important implications for both medical and surgical vitreoretinal disease. The in vitro model presented here provides a method of biocompatibility testing prior to more costly and cumbersome in vivo experiments. The explant culture system imposes reactions within the retina including disruption of layers, cell death and gliosis, and the progression of these reactions can be used for comparison of vitreous substitute candidates. Bio-Alcamid (R) had strong adverse effects on the retina which is consistent with results of prior in vivo trials. PEG gel elicits reactions similar to the control retinas whereas Healaflow (R) shows protection from culture-induced trauma indicating favorable biocompatibility.

  • 5.
    Barth, Henrik
    et al.
    Dept Ophthalmol, Lund Univ, Lund, Sweden.
    Crafoord, Sven W.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Dept Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Arner, Karin
    Dept Ophthalmol, Lund Univ, Lund, Sweden.
    Ghosh, Fredrik K.
    Dept Ophthalmol, Lund Univ, Lund, Sweden.
    Cellular CD68 and CD45r0 positive inflammatory responses of vitrectomy with vitreous substitutes2016In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, no 12Article in journal (Refereed)
  • 6. Bonamy, Anna-Karin E
    et al.
    Holmström, Gerd
    Stephansson, Olof
    Ludvigsson, Jonas F
    Örebro University Hospital.
    Cnattingius, Sven
    Preterm birth and later retinal detachment: a population-based cohort study of more than 3 million children and young adults2013In: 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.

  • 7.
    Bäckman, Anders
    et al.
    Örebro University, School of Medical Sciences. Clinical Research Centre, Örebro University Hospital, Örebro, Sweden.
    Makdoumi, Karim
    Örebro University, School of Medical Sciences. Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden; Centre for Health Care Sciences, Örebro University Hospital, Örebro, Sweden.
    Mortensen, Jes
    Department of Ophthalmology, Ryhov County Hospital, Jönköping, Sweden.
    Crafoord, Sven
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    The efficiency of cross-linking methods in eradication of bacteria is influenced by the riboflavin concentration and the irradiation time of ultraviolet light2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 7, p. 656-661Article in journal (Refereed)
    Abstract [en]

    Purpose: To determine bacterial eradication using numerous riboflavin concentrations and different ultraviolet light A (UVA) radiant and exposure time in an experimental model.

    Methods: Dilutions of Staphylococcus epidermidis were mixed with riboflavin at varying concentrations (0.007-0.09%). Effects on bacterial growth were evaluated after 0, 3, 6, 30 and 60min of UVA exposure (irradiance 30 and 3mW/cm(2)). Standard settings of UVA were compared with high-power UVA approach. Different fluid thicknesses of the exposed dilutions were also examined to improve the model.

    Results: Bacterial eradication (%) was increased after 60 compared with 30min of UVA exposure for concentrations of 0.03-0.07% but not for 0.09% riboflavin. There was a significant difference between the efficacy between 0.03 and 0.09% and eradication dropped from 80% to 50% (p=0.01). A correlation could be calculated for the amount of riboflavin at 60min of UVA and the ability to kill bacteria (p=0.01). The antibacterial effect was more pronounced when the tested bacterial suspension thickness was reduced. High-power UVA method was less potent in microbial elimination, eradicating only 60% of bacteria after 6min versus 97-99% after 60min in the low-power setting, compared with respective controls (p=0.02).

    Conclusions: In these in vitro experiments, a longer UVA exposure time in combination with lower riboflavin levels were found to be favourable in killing bacteria as compared to the standard cross-linking settings. Further studies are needed to evaluate the clinical relevance of these findings.

  • 8.
    Crafoord, Sven
    Örebro University, School of Health and Medical Sciences.
    Do vitreoretinal patients benefit from the use of small-gauge instruments?2008In: Acta Ophthalmologica, ISSN 1755-3768, Vol. 86, no 2, p. 120-121Article in journal (Refereed)
  • 9.
    Crafoord, Sven
    et al.
    Departments of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Andreasson, Sten
    Departments of Ophthalmology, University of Lund, Lund, Sweden.
    Ghosh, Fredrik
    Departments of Ophthalmology, University of Lund, Lund, Sweden.
    Experimental vitreous tamponade using polyalkylimide hydrogel2011In: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 249, no 8, p. 1167-74Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate polyalkylimide as a possible vitreous tamponading agent.

    METHODS: A 20-gauge pars plana vitrectomy and posterior vitreous detachment were performed in the right eye of six pigmented rabbits. Approximately 1 ml of viscoelastic gel, polyalkylimide (Bio-Alcamid) was thereafter injected into the vitreous space. Full-field ERG and intraocular pressure (IOP, Tonopen) was measured pre-and postoperatively at regular intervals up to 28 days. At day 6 or 28, the rabbits were sacrificed and the eyes were examined macroscopically, photographed, and prepared for histological examination with routine microscopy.

    RESULTS: The viscoelastic hydrogel was successfully injected, and remained translucent with preserved gel properties throughout the postoperative period. The postoperative IOP was unchanged compared to preoperative values. Five of six eyes displayed retinal edema or pigmentary changes centrally while the periphery appeared intact. ERG recordings showed a radical decrease in rod- and cone-derived B-wave amplitudes. Histological examination confirmed varying degrees of edema combined with neuronal cell death within the retinal layers in the central part of the fundus, while the peripheral part appeared intact.

    CONCLUSION: Polyalkylimide displays favourable physical properties when used as a vitreous tamponade. However, the hydrogel causes functional and morphological retinal damage when in direct contact with the inner retina. Possible pathological mechanisms include osmotic imbalance and direct toxic effects, and modification of biochemical properties is warranted before clinical use will be possible.

  • 10.
    Crafoord, Sven
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Ghosh, Fredrik
    Department of Ophthalmology, Skåne University Hospital, Lund, Sweden; Lund University, Lund, Sweden.
    Sebag, Jerry
    VMR Institute for Vitreous Macula Retina, Huntington Beach CA, USA; Doheny Eye Institute, Los Angeles CA, USA.
    Vitreous biochemistry and artificial vitreous2014In: Vitreous: in Health and Disease / [ed] Jerry Sebag MD, FACS, FRCOphth, FARVO, New York, USA: Springer, 2014, 1, p. 81-92Chapter in book (Other academic)
  • 11.
    Crafoord, Sven
    et al.
    Örebro University, School of Health and Medical Sciences.
    Karlsson, Niklas
    la Cour, Morten
    Sheathotomy in complicated cases of branch retinal vein occlusion2008In: Acta Ophthalmologica, ISSN 1755-3768, Vol. 86, no 2, p. 146-150Article in journal (Refereed)
    Abstract [en]

    Purpose: To report the clinical experience and results of using a microsurgical technique to decompress the arteriovenous connection in complicated branch retinal vein occlusion (BRVO) combined with haemorrhage, oedema and ischaemia.

    Methods: We carried out a retrospective, non-randomized, interventional case study of the surgical sheathotomy decompression procedure. We enrolled 12 patients (seven women, five men; median age 64 years) with BRVO and decreased visual acuity (VA) caused by haemorrhage, oedema and ischaemia. The mean duration of thrombosis was 7 months (2–15 months). The patients were examined for pre- and postoperative best corrected VA (BCVA), intraocular pressure (IOP) and fundus photography. Ten patients were examined with fluorescein angiography and eight with ocular coherence tomography (OCT). Postoperative progression of cataract was recorded, as were other complications. The mean follow-up time was 20 months (8–39 months).

    Results: Best corrected VA had improved in nine patients, was unchanged in one patient and had deteriorated in two patients at the last follow-up. Noted complications were venous haemorrhage at surgery in five patients, retinal detachment in one patient and progression of cataract in four patients.

    Conclusions: Microsurgical treatment with sheathotomy of BRVO is a technically feasible procedure with few complications. Postoperative increased reperfusion could explain the resolution of macular haemorrhage, oedema and ischaemia, and may improve visual function in patients with this common vascular eye disease.

  • 12.
    Domkin, Dmitry
    et al.
    Centre for Musculoskeletal Research, Department of Occupational and Public Health Sciences, Faculty of Health and Occupational Studies, University of Gävle, Gävle, Sweden.
    Richter, Hans O.
    Centre for Musculoskeletal Research, Department of Occupational and Public Health Sciences, Faculty of Health and Occupational Studies, University of Gävle, Gävle, Sweden.
    Zetterlund, Christina
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Low Vision Centre, Örebro County Council, Örebro, Sweden; Centre for Rehabilitation Research, Örebro County Council, Örebro, Sweden; .
    Lundqvist, Lars-Olov
    Örebro University, School of Law, Psychology and Social Work. Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Centre for Rehabilitation Research, Örebro County Council, Örebro, Sweden.
    Effect of reduced visual acuity on precision of two-dimensional tracing movements2016In: Journal of Optometry, ISSN 1888-4296, Vol. 9, no 2, p. 93-101Article in journal (Refereed)
    Abstract [en]

    Purpose: We intended to assess consequences of reduced visual acuity for performance in a natural simple motor task (tracing) using objective kinematic performance measures. Specifically, we intended to elucidate the kind of relationship between the task performance and best corrected binocular visual acuity and to determine the threshold of visual acuity when task performance starts to deteriorate.

    Methods: Ninety-five individuals with different best corrected visual acuity participated in the study (age 49±12 years, mean±SD, 27 men and 68 women). The participants manually traced maze-like visual patterns of different spatial complexity presented on the screen of a portable notebook computer using Clinical Kinematic Assessment Tool software. Tracing error was computed as performance measure in each trial with a spatial pattern matching technique - rigid point set registration method.

    Results: The segmented linear regression analysis showed that the relation between visual acuity and tracing errors was best described with a regression function having a break point between two data segments. Tracing performance was unaffected by values of visual acuity below 0.2 on logMAR scale, but when logMAR values increased above this critical limit (i.e. when visual acuity is further reduced), tracing errors linearly increased. The rate of the increase of the tracing error correlated with the complexity of visual stimulus shape.

    Conclusion: Testing of fine motor functions with objective kinematic measures during visuomotor tasks may help differentiating between actual effects of reduced visual acuity on eye-hand coordination in individuals with similar levels of impairment of visual acuity.

  • 13.
    Ejdervik Lindblad, Birgitta
    et al.
    Örebro University, School of Medical Sciences. Department of Ophthalmology.
    Håkansson, Niclas
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Wolk, Alicja
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Metabolic syndrome and some of its components in relation to risk of cataract extraction: A prospective cohort study of men2018In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate the relationship between metabolic syndrome and some of its components with the incidence of cataract extraction.

    METHODS: A population-based prospective cohort with a total of 45 049 men, aged 45-79 years, from the Cohort of Swedish Men completed in 1997 a self-administered questionnaire concerning anthropometric measurements and lifestyle factors. The men were followed from 1 January 1998 through 31 December 2012, and the cohort was matched with registers of cataract extraction. The main outcome measure was incident cases of age-related cataract extraction.

    RESULTS: Over the 15-years of follow-up, 7573 incident cases of cataract extraction were identified. After controlling for potential confounders, the association between single components of metabolic syndrome, abdominal adiposity, diabetes and hypertension and risk of cataract extraction was rate ratio (RR): 1.04; 95% confidence interval (CI): 0.99-1.10, RR: 1.77; 95% CI: 1.64-1.92 and RR: 1.06; 95% CI 1.00-1.13, respectively. The risk of cataract extraction increased with increasing numbers of metabolic syndrome components (p < 0.0001). Men aged 65 years or younger at baseline with all three components of the metabolic syndrome had a relative risk of 2.43 (95% CI: 1.95-3.01) for cataract extraction.

    CONCLUSION: In this cohort of middle-aged and elderly men, metabolic syndrome with the combination of abdominal adiposity, diabetes and hypertension was associated with an increased risk for cataract extraction, especially among men aged 65 years or younger. These findings put emphasis on the importance of weight control and healthy lifestyle behaviours in order to prevent cataract.

  • 14. Elefteria, Dhima
    et al.
    Ejdervik Lindblad, Birgitta
    Örebro University, School of Medical Sciences.
    Central serous chorioretinopathy as a first sign of severe undiagnosed SLE in a pregnant woman2017Conference paper (Refereed)
  • 15.
    Gili, Nasser J.
    et al.
    Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Norén, Torbjörn
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine.
    Törnquist, Eva
    Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Crafoord, Sven
    Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Bäckman, Anders
    Örebro University, School of Medical Sciences. Department of Clinical Research Laboratory.
    Preoperative preparation of eye with chlorhexidine solution significantly reduces bacterial load prior to 23-gauge vitrectomy in Swedish health care2018In: BMC Ophthalmology, ISSN 1471-2415, E-ISSN 1471-2415, Vol. 18, article id 167Article in journal (Refereed)
    Abstract [en]

    Background: Bacteria in the conjunctiva present a potential risk of vitreous cavity infection during 23-gauge pars plana vitrectomy (PPV). Current preoperative procedures used in Sweden include irrigation with chlorhexidine solution (CHX) 0.05% only and no iodine solutions. We evaluated the bacterial diversity and load before and after this single antibacterial measure.

    Methods: In a prospective, consecutive cohort we investigated bacterial growth in samples from 40 eyes in 39 consecutive individuals subjected to vitrectomy. A conjunctival specimen was collected from each preoperative patient before and after irrigating of eye with CHX, 0.05% solution. Iodine was not used during any part of the surgery. One drop of chloramphenicol was administered prior to surgery. Samples from vitreous cavity were collected at the beginning and end of vitrectomy. All conjunctival specimens were cultured for different species and quantified using colony forming units (CFU).

    Results: There was a significant 82% reduction in the total number of CFUs for all bacteria in all eyes (P < 0.0001), and 90% reduction for coagulase negative staphylococci (CoNS) alone (P = 0.0002). The number of eyes with positive bacterial growth in conjunctival samples decreased from 33 to 18 after irrigation with CHX (P = 0.0023). The most common bacteria prior to surgery were CoNS (70%), Propionibacterium acnes (55%) and Corynebacterium species (36%). No case of post-vitrectomy endophthalmitis was reported during mean follow-up time, which was 4.6 +/- 2.3 (range; 1.5 to 9) months.

    Conclusions: Patients undergoing PPV harbored bacteria in conjunctiva capable of causing post-vitrectomy endophthalmitis. Preoperative preparation with CHX significantly reduced the bacterial load in the conjunctival samples subsequently leading to very low inoculation rates in recovered vitreous samples. Thus, CHX used as a single disinfectant agent might be an effective preoperative procedure for eye surgery in Sweden. This is a relatively small study but the results could be a reference for other intraocular surgeries.

  • 16.
    Joussen, Antonia M
    et al.
    Department of Ophthalmology, Charité, University Medicine, Berlin, Germany.
    Rizzo, Stanislao
    U.O.Chirurgia Oftalmica, Azienda Ospedaliero, Universitaria Pisana, Pisa, Italy.
    Kirchhof, Bernd
    Department of Vitreoretinal Surgery, University of Cologne, Cologne, Germany.
    Schrage, Norbert
    Augenklinik Kön-Merheim, Cologne, Germany.
    Li, Xiaoxin
    Beijing University, Beijing, China.
    Lente, Christina
    Department of Medical Statistics, Rheinisch-Westfälische Technische Hochschule, Aachen, Germany.
    Hilgers, Ralf-Dieter
    Department of Medical Statistics, Rheinisch-Westfälische Technische Hochschule, Aachen, Germany.
    Crafoord, Sven
    Örebro University, School of Medicine, Örebro University, Sweden.
    Heavy silicone oil versus standard silicone oil in as vitreous tamponade in inferior PVR (HSO Study): interim analysis2011In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 89, no 6, p. e483-e489Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The Heavy Silicone Oil versus Standard Silicone Oil Study (HSO study) is designed to answer the question whether a heavier-than-water tamponade improves the prognosis of eyes with proliferative vitreoretinopathy (PVR) of the lower retina.

    METHODS: The HSO Study is a multicentre, randomized, prospective, controlled clinical trial stratified by surgeon comparing two endotamponades within a two-arm parallel-group design. Patients with inferiorly and posteriorly located PVR grade C-A6 were randomized to either HSO or standard silicone oil as a tamponading agent. The main end-point criteria are complete retinal attachment at 12 months and change in visual acuity (VA) 12 months postoperatively compared to the preoperative VA.

    RESULTS: Forty-six patients treated with HSO were compared to 47 patients treated with standard silicone oil. There was no difference among the groups regarding baseline data. Three patients in the HSO and five patients in the standard silicone oil group fulfilled intraoperative exclusion criteria. There was no significant difference between both groups regarding anatomical success. Neither noninferiority nor superiority was shown with regard to final acuity.

    CONCLUSIONS: The HSO Study is the first randomized prospective clinical trial to compare heavy and standard silicone oil in patients with PVR of the lower retina. The intermediate results failed to demonstrate superiority of a heavy tamponade.

  • 17.
    Lindblad, Birgitta Ejdervik
    et al.
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Ophthalmology, Sundsvall Hospital, Sundsvall, Sweden.
    Håkansson, Niclas
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Philipson, Bo
    Stockholm Eye Clinic, H.M. Queen Sophia Hospital, Stockholm, Sweden.
    Wolk, Alicja
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Alcohol consumption and risk of cataract extraction: a prospective cohort study of women2007In: Ophthalmology (Rochester, Minn.), ISSN 0161-6420, E-ISSN 1549-4713, Vol. 114, no 4, p. 680-685Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate the association between alcohol consumption and the risk of cataract extraction.

    DESIGN: Population-based prospective cohort study.

    PARTICIPANTS: A total of 34,713 women participating in the Swedish Mammography Cohort, age 49 to 83 years, completed in 1997 a self-administered questionnaire about alcohol, smoking, and other lifestyle factors.

    METHODS: The women were followed from September 1997 through September 2004. The cohort was matched with registers of cataract extraction from the study area.

    MAIN OUTCOME MEASURES: Incident surgical extraction of age-related cataract.

    RESULTS: During 84 months of follow-up, we found 3587 incident cases of age-related cataract extraction. Compared with never drinkers, the relative risk of cataract extraction among current drinkers was 1.11 (95% confidence interval [CI] 1.02-1.21) after adjustment for age and other potential risk factors. In multivariate analysis, an increment of 13 g alcohol intake per day (corresponding to 1 drink = 330 ml of beer, 150 ml of wine, or 45 ml of liquor) was associated with a 7% increased risk of cataract extraction (relative risk, 1.07; 95% CI 1.02-1.12). Mean age at cataract extraction among nonsmoking women who used alcohol was 75 years, compared with 77.6 years among never drinkers.

    CONCLUSIONS: These prospective data suggest that daily use of >/=1 alcoholic drinks was associated with a modest increase of risk for cataract extraction. The risk increased with increasing alcohol consumption.

  • 18.
    Lindblad, Birgitta Ejdervik
    et al.
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Ophthalmology, Sundsvall Hospital, Sundsvall, Sweden.
    Håkansson, Niclas
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Philipson, Bo
    Stockholm Eye Clinic, H.M. Queen Sophia Hospital, Stockholm, Sweden.
    Wolk, Alicja
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Hormone replacement therapy in relation to risk of cataract extraction: a prospective study of women2010In: Ophthalmology (Rochester, Minn.), ISSN 0161-6420, E-ISSN 1549-4713, Vol. 117, no 3, p. 424-430Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the association between hormone replacement therapy (HRT) and the incidence of cataract extraction among postmenopausal women.

    DESIGN: Population-based, prospective cohort study.

    PARTICIPANTS: A total of 30 861 postmenopausal women participating in the Swedish Mammography Cohort, age 49 to 83 years, who completed a self-administered questionnaire in 1997 about hormone status, HRT, and lifestyle factors.

    METHODS: The women were followed from September 1997 through October 2005. The cohort was matched with registers of cataract extraction in the study area.

    MAIN OUTCOME MEASURES: Incident operative extraction of age-related cataract.

    RESULTS: We identified 4324 incident cases of cataract extractions during 98 months of follow-up. In multivariate adjusted analysis, ever use of HRT was associated with a 14% increased risk of cataract extraction (rate ratio [RR], 1.14; 95% confidence interval [CI], 1.07-1.21) compared with those who never used HRT. Current use of HRT was associated with an 18% increased risk of cataract extraction (RR, 1.18; 95% CI, 1.10-1.26). A significant linear trend was observed where increasing duration of HRT usage resulted in an increased risk of cataract extraction (P for trend = 0.006). Multivariate RR for current HRT usage for >10 years was 1.20 (95% CI, 1.06-1.36; P for trend = 0.001). Among women drinking on average >1 drink of alcohol per day, current HRT users had a 42% increased risk (RR, 1.42; 95% CI, 1.11-1.80) for cataract extraction, compared with women who neither used HRT nor alcohol. The risk of cataract extraction among current users of HRT was similar among current smokers and those who never smoked.

    CONCLUSIONS: Our prospective, population-based study indicates that postmenopausal women using HRT for a long period of time may be at an increased risk for cataract extraction, especially those drinking >1 alcoholic drink daily.

  • 19.
    Lindblad, Birgitta Ejdervik
    et al.
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Ophthalmology, Sundsvall Hospital, Sundsvall, Sweden.
    Håkansson, Niclas
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Philipson, Bo
    Stockholm Eye Clinic, H. M. Queen Sophia Hospital, Stockholm, Sweden.
    Wolk, Alicja
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Metabolic syndrome components in relation to risk of cataract extraction: a prospective cohort study of women2008In: Ophthalmology (Rochester, Minn.), ISSN 0161-6420, E-ISSN 1549-4713, Vol. 115, no 10, p. 1687-1692Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the association between metabolic syndrome and some of its components with the incidence of cataract extraction.

    DESIGN: Population-based prospective cohort study.

    PARTICIPANTS: A total of 35,369 women, participating in the Swedish Mammography Cohort, aged 49 to 83 years, who completed a self-administered questionnaire about anthropometric measurements and lifestyle factors in 1997.

    METHODS: The women were followed from September of 1997 to October of 2005. The cohort was matched with registers of cataract extraction in the study area.

    MAIN OUTCOME MEASURES: Incident surgical extraction of age-related cataract.

    RESULTS: We identified 4508 incident cases of cataract extractions during 98 months of follow-up. In multivariate analysis, women with a waist circumference >or=80 cm had an 8% increased risk of cataract extraction (rate ratio [RR], 1.08; 95% confidence interval [CI], 0.99-1.17). Women with diabetes had a 43% increased risk of cataract extraction (RR, 1.43; 95% CI, 1.10-1.86), and hypertension was associated with a 12% increased risk (RR, 1.12; 95% CI, 0.99-1.26). Women with all 3 components of the metabolic syndrome (waist >or=80 cm, diabetes, and hypertension) had a 68% increased risk of cataract extraction (RR, 1.68; 95% CI, 1.40-2.02) compared with women without any of these components. Among women aged less than 65 years at baseline with all 3 components of metabolic syndrome, the risk of cataract extraction was approximately 3-fold more (RR, 2.80; CI, 1.94-4.03).

    CONCLUSIONS: Metabolic syndrome and its components, abdominal adiposity, diabetes, and hypertension, seem to be associated with an increased risk for cataract extraction, especially among women aged less than 65 years.

  • 20.
    Lindblad, Birgitta Ejdervik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Håkansson, Niclas
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Wolk, Alicja
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Smoking cessation and the risk of cataract: a prospective cohort study of cataract extraction among men2014In: JAMA ophthalmology, ISSN 2168-6165, E-ISSN 2168-6173, Vol. 132, no 3, p. 253-7Article in journal (Refereed)
    Abstract [en]

    Importance: Smoking is a risk factor for cataract development, but the effect of smoking cessation on the risk of cataract is uncertain.

    Objective: To examine the association between smoking cessation and the risk of cataract extraction.

    Design, setting, and participants: A total of 44,371 men, participating in the Cohort of Swedish Men, aged 45 to 79 years, who in 1997 completed a self-administered questionnaire on smoking habits and lifestyle factors. The men were followed up from January 1, 1998, through December 31, 2009. The cohort was matched with the Swedish National Day-Surgery Register and local registers of cataract extraction in the study area.

    Main outcomes and measures: Incident cases of age-related cataract extraction.

    Results: During 12 years of follow-up, we identified 5713 incident cases of age-related cataract extraction. Smoking intensity and cumulative dose of smoking were associated with an increased risk of cataract extraction (P for trend <.001). Current smokers of more than 15 cigarettes per day had a 42% increased risk of cataract extraction (rate ratio, 1.42; 95% CI, 1.28-1.58) compared with never smokers after adjustment for age and other potential risk factors. Smoking cessation significantly decreased the risk for cataract extraction with time (P for trend <.001). After more than 20 years since stopping smoking, men with a mean smoking intensity of more than 15 cigarettes per day had a 21% increased risk of cataract extraction (rate ratio, 1.21; 95% CI, 1.06-1.39) compared with never smokers. Among men who smoked 15 cigarettes or less per day, the effect of smoking cessation was observed earlier, but more than 2 decades after smoking cessation, the risk of cataract extraction did not decrease to the level of never smokers (rate ratio, 1.13; 95% CI, 1.04-1.24).

    Conclusion and relevance: Smoking cessation seems to decrease the risk of cataract extraction with time, although the risk persists for decades. The higher the intensity of smoking, the longer it takes for the increased risk to decline. These findings emphasize the importance of early smoking cessation and preferably the avoidance of smoking.

  • 21.
    Liu, Yangfan P.
    et al.
    Center for Human Disease Modeling, Duke University School of Medicine, Durham NC, USA.
    Bosch, Danielle G. M.
    Bartiméus, Institute for the Visually Impaired, Zeist, The Netherlands; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
    Siemiatkowska, Anna M.
    Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
    Dahl Rendtorff, Nanna
    Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, ICMM, University of Copenhagen, Copenhagen, Denmark; Department of Audiology, Bispebjerg Hospital and Rigshospitalet, Copenhagen, Denmark.
    Boonstra, F. Nienke
    Bartiméus, Institute for the Visually Impaired, Zeist, The Netherlands; Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
    Möller, Claes
    Örebro University, School of Health Sciences. Örebro University Hospital. Audiological Research Centre, Örebro University Hospital, Örebro, Sweden.
    Tranebjaerg, Lisbeth
    Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine ICMM, University of Copenhagen, Copenhagen, Denmark; Department of Audiology, Bispebjerg Hospital and Rigshospitalet, Copenhagen, Denmark.
    Katsanis, Nicholas
    Center for Human Disease Modeling, Duke University School of Medicine, Durham NC, USA.
    Cremers, Frans P. M.
    Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
    Putative digenic inheritance of heterozygous RP1L1 and C2orf71 null mutations in syndromic retinal dystrophy2017In: Ophthalmic Genetics, ISSN 1381-6810, E-ISSN 1744-5094, Vol. 38, no 2, p. 127-132Article in journal (Refereed)
    Abstract [en]

    Background: Retinitis pigmentosa (RP) is the most common cause of inherited retinal degeneration and can occur in non-syndromic and syndromic forms. Syndromic RP is accompanied by other symptoms such as intellectual disability, hearing loss, or congenital abnormalities. Both forms are known to exhibit complex genetic interactions that can modulate the penetrance and expressivity of the phenotype.

    Materials and methods: In an individual with atypical RP, hearing loss, ataxia and cerebellar atrophy, whole exome sequencing was performed. The candidate pathogenic variants were tested by developing an in vivo zebrafish model and assaying for retinal and cerebellar integrity.

    Results: Exome sequencing revealed a complex heterozygous protein-truncating mutation in RP1L1, p.[(Lys111Glnfs*27; Gln2373*)], and a heterozygous nonsense mutation in C2orf71, p.(Ser512*). Mutations in both genes have previously been implicated in autosomal recessive non-syndromic RP, raising the possibility of a digenic model in this family. Functional testing in a zebrafish model for two key phenotypes of the affected person showed that the combinatorial suppression of rp1l1 and c2orf71l induced discrete pathology in terms of reduction of eye size with concomitant loss of rhodopsin in the photoreceptors, and disorganization of the cerebellum.

    Conclusions: We propose that the combination of heterozygous loss-of-function mutations in these genes drives syndromic retinal dystrophy, likely through the genetic interaction of at least two loci. Haploinsufficiency at each of these loci is insufficient to induce overt pathology.

  • 22.
    Lundqvist, Lars-Olov
    et al.
    Örebro University, School of Law, Psychology and Social Work.
    Zetterlund, Christina
    Örebro University, School of Medical Sciences. The Low Vision Center, Region Örebro County, Örebro, Sweden .
    Richter, Hans O.
    Department of Occupational and Public Health Sciences, Faculty of Health and Occupational Studies, Centre for Musculoskeletal Research, University of Gävle, Gävle, Sweden .
    Reliability and Validity of the Visual, Musculoskeletal, and Balance Complaints Questionnaire2016In: Optometry and Vision Science, ISSN 1040-5488, E-ISSN 1538-9235, Vol. 93, no 9, p. 1147-1157Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate the reliability and validity of the 15-item Visual, Musculoskeletal, and Balance Complaints Questionnaire (VMB) for people with visual impairments, using confirmatory factor analysis (CFA) and with Rasch analysis for use as an outcome measure.

    Methods: Two studies evaluated the VMB. In Study 1, VMB data were collected from 1249 out of 3063 individuals between 18 and 104 years old who were registered at a low vision center. CFA evaluated VMB factor structure and Rasch analysis evaluated VMB scale properties. In Study 2, a subsample of 52 individuals between 27 and 67 years old with visual impairments underwent further measurements. Visual clinical assessments, neck/scapular pain, and balance assessments were collected to evaluate the convergent validity of the VMB (i.e. the domain relationship with other, theoretically predicted measures).

    Results: CFA supported the a priori three-factor structure of the VMB. The factor loadings of the items on their respective domains were all statistically significant. Rasch analysis indicated disordered categories and the original 10-point scale was subsequently replaced with a 5-point scale. Each VMB domain fitted the Rasch model, showing good metric properties, including unidimensionality (explained variances ≥66% and eigenvalues <1.9), person separation (1.86 to 2.29), reliability (0.87 to 0.94), item fit (infit MnSq's >0.72 and outfit MnSq's <1.47), targeting (0.30 to 0.50 logits), and insignificant differential item functioning (all DIFs but one <0.50 logits) from gender, age, and visual status. The three VMB domains correlated significantly with relevant visual, musculoskeletal, and balance assessments, demonstrating adequate convergent validity of the VMB.

    Conclusions: The VMB is a simple, inexpensive, and quick yet reliable and valid way to screen and evaluate concurrent visual, musculoskeletal, and balance complaints, with contribution to epidemiological and intervention research and potential clinical implications for the field of health services and low vision rehabilitation.

  • 23.
    Makdoumi, Karim
    et al.
    Örebro University, School of Medical Sciences. Department of Ophthalmology , Örebro University Hospital, Örebro, Sweden.
    Bäckman, Anders
    Örebro University, School of Medical Sciences. Clinical Research Centre, Örebro University Hospital, Örebro, Sweden.
    Photodynamic UVA-riboflavin bacterial elimination in antibiotic-resistant bacteria2016In: Clinical and Experimental Ophthalmology, ISSN 1442-6404, E-ISSN 1442-9071, Vol. 44, no 7, p. 582-586Article in journal (Refereed)
    Abstract [en]

    Background: To evaluate the bactericidal effect of clinical ultraviolet A (UVA) settings used in photoactivated chromophore for infectious keratitis (PACK)-collagen cross-linking (CXL) in antibiotic-resistant and non-resistant bacterial strains.

    Methods: Well-characterized bacterial strains from clinical isolates, without and with antibiotic resistance, were studied in a pairwise comparison. The evaluated pathogens were Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus faecalis. Bacteria were dispersed in PBS and diluted to a concentration of approximately 4x10(5)/ml. Riboflavin was added to a concentration of 0.01%. By spreading the solution on a microscope slide, a fluid film layer, with a thickness of around 400mm, was formed and UVA exposure followed. Eight separate exposures were made for each strain (n=8). The degree of elimination in resistant and non-resistant pathogens was compared.

    Results: The bactericidal efficacy of exposure differed between the tested microorganisms, and the mean elimination ranged between 60 and 92%, being most extensive in both of the evaluated Pseudomonas strains and least in the E. faecalis strains. Similar reductions were seen in antibiotic-resistant and non-resistant strains, with the exception of S. aureus, in which the resistant strain metchicillin-resistant Staphylococcus aureus (MRSA) was eradicated in a greater extent than the non-resistant strain (P=0.030).

    Conclusion: UVA-riboflavin settings used in PACK-CXL are effective in reducing both antibiotic-resistant and non-resistant bacteria. Antibiotic resistance does not appear to be protective against the photooxidative exposure.

  • 24.
    Makdoumi, Karim
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Ophthalmology, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Bäckman, Anders
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clinical Research Centre, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Mortensen, Jes
    Dept. Ophthalmology, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Magnuson, Anders
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clinical Epidemiology and Biostatistic Unit, Örebro University Hospital, Örebro, Sweden.
    Crafoord, Sven
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Comparison of UVA- and UVA/riboflavin-induced growth inhibition of Acanthamoeba Castellanii2013In: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 251, no 2, p. 509-514Article in journal (Refereed)
    Abstract [en]

    Purpose To investigate whether ultraviolet light (UVA) at 365 nm can inhibit/eliminate Acanthamoeba growth and if riboflavin would potentiate such an association.

    Method: Acanthamoeba castellanii in a fluid medium with a concentration of approximately 1.7 x 10(4) protozoa/ml were prepared with (0.01 %) and without riboflavin. Exposure of UVA (dose 5.475 J/cm(2)) took place twice, with each illumination period followed by culturing of 10 mu l in peptone yeast-extract glucose (PYG) medium for 7 days. Every suspension prepared had a non-exposed control solution. Determination of Acanthamoeba was conducted daily, by count in Burker chamber days 4 through 7 after exposure. Statistical analysis was done by repeated-measurement ANOVA and post-hoc analysis for unpaired samples.

    Results: The exposure of ultraviolet light resulted in an inhibited growth of Acanthamoeba compared to the non-exposed solutions, with a statistically significant reduction over time (p = 0.0003). The addition of riboflavin did not amplify the effect, and there were no tendencies for an interaction effect between UVA and riboflavin. The antiprotozoal effect of the UVA wavelength, utilized in CXL, is solely mediated by ultraviolet light, and riboflavin does not seem to amplify the antimicrobial efficacy.

  • 25.
    Makdoumi, Karim
    et al.
    Örebro University, School of Health and Medical Sciences. Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Crafoord, Sven
    Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Vasoproliferative retinal tumours in a Swedish population2011In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 89, no 1, p. 91-94Article in journal (Refereed)
    Abstract [en]

    Purpose: To describe the clinical appearance and the visual outcome of a cohort of patients with vasoproliferative retinal tumours (VPRTs) that were diagnosed and treated between 2002 and 2007 at the University Hospital of Orebro.

    Methods: Nine patients with diagnosed VPRTs were included in a retrospective study. The mean age at the time of diagnosis was 50.2 years (range 7-74 years). Follow-up time ranged between 14 and 83 months (mean 42.6). Nine out of ten eyes received cryotherapy; six eyes were also treated with photocoagulation. One patient was treated with intravitreal injections of ranibizumab (Lucentis((R))) and another was referred for brachytherapy. Because of persisting macular oedema, one eye was treated with intravitreal injection of triamcinolon.

    Results: Of the treated eyes, one had anterior uveitis, six had macular oedema at baseline and four had an exudative retinal detachment at the time of diagnosis. Seven eyes underwent vitrectomy because of epiretinal membranes. Visual acuity at diagnosis was 0.21 (mean) (range 0.02-0.6) and at latest check-up 0.30 (mean) (range light perception (LP)-1.0), with improvement in six eyes and deterioration in two. Two out of four patients with retinal detachment were successfully treated surgically.

    Conclusion: VPRTs are benign intraretinal changes. Several complications are associated with this condition. All patients in this study had symptom-giving tumours and six patients (six eyes) already had profound macular oedema at presentation. In these cases, when complications have already developed, the final visual prognosis is poor, thereby making it important to detect these tumours early. The patient who received anti-vascular endothelial growth factor (VEGF; Lucentis) therapy showed a slow improvement and distinct regression in exudations during the follow-up time. However, no increase in visual acuity was seen. At latest examination a peripheral exudative retinal detachment was still observed. Whether anti-VEGF treatment is effective, as either an alternative or complementary therapy, must be established in the future.

  • 26.
    Makdoumi, Karim
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Goodrich, Ray
    Terumo BCT Inc., Lakewood CO, USA.
    Bäckman, Anders
    Örebro University, School of Medical Sciences. Örebro University Hospital. , Örebro University Hospital, Örebro, Sweden.
    Photochemical eradication of methicillin-resistant Staphylococcus aureus by blue light activation of riboflavin2017In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 95, no 5, p. 498-502Article in journal (Refereed)
    Abstract [en]

    Purpose: To compare elimination of methicillin-resistant Staphylococcus aureus (MRSA) by exposure of blue light alone and with riboflavin.

    Methods: A reference strain of MRSA was cultured and diluted in PBS with and without riboflavin (0.01%). Fifteen microlitre was added on a microscope slide, creating a fluid layer with a thickness of around 400 microns. Both of the bacterial suspensions were exposed to blue light, and the effect between exposure with and without riboflavin was compared. Evaluation involved two different wavelengths (412 and 450 nm) of blue light with a lower (5.4 J/cm(2) ) and higher dose (approximately 28.5 J/cm(2) ). The effect of 412 nm light was also evaluated for a thicker fluid layer (1.17 mm). After exposure, colony-forming units (CFUs) were determined for each solution. All measurements were repeated eight times.

    Results: The reductions in bacteria were similar for both wavelengths. With riboflavin, a statistically significant elimination was observed for both 412 and 450 nm (p < 0.001). At both dosages, the mean reduction was more pronounced with the presence of riboflavin than without it. Using the higher dose, CFU reduction was 99% and 98%, respectively, for 412 and 450 nm light. The bactericidal efficacy was high also in the deeper fluid layer (93%, higher dose).

    Conclusion: Riboflavin enhanced the antibacterial effect on the exposed MRSA strain of blue light for both 412 and 450 nm blue light. This indicates that blue light could be considered for possible implementation in deep corneal infections.

  • 27.
    Makdoumi, Karim
    et al.
    Örebro University Hospital.
    Mortensen, Jes
    Orebro Univ Hosp, Orebro, Sweden..
    Crafoord, Sven
    Örebro University Hospital.
    Response to: evaluation of combined riboflavin and ultraviolet A as an alternative treatment for keratitis2013In: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 251, no 3, p. 997-998Article in journal (Refereed)
  • 28.
    Makdoumi, Karim
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Nilsson, Torbjörn K.
    Department of Medical Biosciences/Clinical Chemistry, Umeå University, Umeå, Sweden; Faculty of Medicine and Health Department of Biomedicine, Örebro University, Örebro, Sweden.
    Crafoord, Sven
    Örebro University, School of Medical Sciences. Department of Ophthalmology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Levels of beta-trace protein in optic disc pit with macular detachment2017In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 95, no 8, p. 815-819Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: To report beta-trace protein (βTP) levels in the subretinal fluid (SRF) of four patients with a macular detachment associated with optic disc pit (ODP).

    METHODS: Four patients with a serous retinal detachment involving the macula was operated by pars plana vitrectomy (PPV) with C2 F6 gas tamponade and peeling of internal limiting membrane (ILM). Patients with a follow-up period exceeding one year postoperatively were included in the study. The SRF was drained using a fine cannula without laser photocoagulation, and the samples were analysed using particle-enhancing nephelometry. The levels of βTP were compared to 20 routine cerebrospinal fluid (CSF) samples.

    RESULTS: In four of the five samples from SRF had relatively low βTP levels, with a mean concentration of 6.6 mg/l (range 2.0 to 23.1 mg/l) compared to 16.0 mg/l (range 6.3-26.8 mg/l) in CSF. The only SRF sample within the range corresponding to normal CSF was the first sample from patient 4, and the analysis of the renewed aspirate during the second operation was 2.8 mg/l. Postoperatively, the regression of SRF was slow, but regression of SRF in the foveal region took place in all cases; however, visual acuity (VA) was improved in only half of the patients.

    CONCLUSION: The results from the analysed SRF regarding βTP concentration in these patients indicate that the SRF in ODP is not identical to CSF, as the concentrations of βTP differ.

  • 29.
    Malm, Eva
    et al.
    Department of Ophthalmology, Skåne University Hospital, Lund, Sweden.
    Ponjavic, Vesna
    Department of Ophthalmology, Skåne University Hospital, Lund, Sweden.
    Möller, Claes
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Audiology, Swedish Institute of Disability Research, Örebro University Hospital, Örebro, Sweden.
    Kimberling, William J.
    Department of Ophthalmology and Visual Science, Iowa University Carver School of Medicine, Iowa City IA, United States; Usher Syndrome Center, BoysTown National Research Hospital, Omaha NE, United States.
    Andréasson, Sten
    Department of Ophthalmology, Skåne University Hospital, Lund, Sweden.
    Phenotypes in defined genotypes including siblings with Usher syndrome2011In: Ophthalmic Genetics, ISSN 1381-6810, E-ISSN 1744-5094, Vol. 32, no 2, p. 65-74Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To characterize visual function in defined genotypes including siblings with Usher syndrome.

    METHODS: Thirteen patients with phenotypically different subtypes of Usher syndrome, including 3 families with affected siblings, were selected. Genetic analysis and ophthalmological examinations including visual fields, full-field electroretinography (ERG), multifocal electroretinography (mf ERG), and optical coherence tomography (OCT) were assessed. The patients' degree of visual handicap was evaluated by a questionnaire (ADL).

    RESULTS: Twelve of thirteen patients were genotyped as Usher 1B, 1D, 1F, 2A, 2C or 3A. In 12 of 13 patients examined with ERG the 30 Hz flickering light response revealed remaining cone function. In 3 of the patients with Usher type 1 mf ERG demonstrated a specific pattern, with a sharp distinction between the area with reduced function and the central area with remaining macular function and normal peak time. OCT demonstrated loss of foveal depression with distortion of the foveal architecture in the macula in all patients. The foveal thickness ranged from 159 to 384 µm and was not correlated to retinal function. Three siblings shared the same mutation for Usher 2C but in contrast to previous reports regarding this genotype, 1 of them diverged in phenotype with substantially normal visual fields, almost normal OCT and mf ERG findings, and only moderately reduced rod and cone function according to ERG.

    CONCLUSIONS: Evaluation of visual function comprising both the severity of the rod cone degeneration and the function in the macular region confirm phenotypical heterogeneity within siblings and between different genotypes of Usher syndrome.

  • 30.
    Malm, Eva
    et al.
    Department of Ophthalmology, Lund University Hospital, Lund, Sweden.
    Ponjavic, Vesna
    Department of Ophthalmology, Lund University Hospital, Lund, Sweden.
    Möller, Claes
    Kimberling, William J.
    Stone, Edwin S.
    Andréasson, Sten
    Department of Ophthalmology, Lund University Hospital, Lund, Sweden.
    Alteration of rod and cone function in children with Usher syndrome2011In: European Journal of Ophthalmology, ISSN 1120-6721, E-ISSN 1724-6016, Vol. 21, no 1, p. 30-38Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate the retinal function, with emphasis on phenotype and rate of progression, in infants and children with different genotypes of Usher syndrome.

    Methods: Fourteen children (2-10 years of age) with retinitis pigmentosa and hearing impairment were examined with full-field electroretinography (ERG) during general anesthesia, ophthalmologic examination, and genetic analysis. Five children were repeatedly examined (follow-up 5-10 years) with full-field ERG under local anesthesia and in 2 children multifocal ERG and optical coherence tomography (OCT) were performed. These results were compared to full-field ERG data from 58 children without retinal eye disorder.

    Results: Six children were genotyped as Usher 1B, 2A, and 3A. Full-field ERG demonstrated early alterations corresponding to a rod-cone dystrophy in all children. A remaining rod function could be verified in the majority of the children up to 4 years of age. After 4 years of age, there was a further deterioration of the rod function; the progress was severe in Usher types 1 and 2 and moderate in Usher type 3. In all children, the cone function was moderately reduced, in a few cases almost normal. The results from the 58 children without retinal disorder confirm that full-field ERG during general anesthesia is reliable. Multifocal ERG confirmed a preserved central cone function and in OCT there were discrete structural alterations.

    Conclusions: Full-field ERG during general anesthesia in children with Usher syndrome demonstrates variable phenotypes and different degrees in rate of progression during childhood.

  • 31. Malm, Eva
    et al.
    Ponjavic, Vesna
    Nishina, Patsy M.
    Naggert, Jürgen K.
    Hinman, Elizabeth G.
    Andréasson, Sten
    Marshall, Jan D.
    Möller, Claes
    Örebro University, School of Health and Medical Sciences.
    Full-field electroretinography and marked variability in clinical phenotype of Alström syndrome2008In: Archives of ophthalmology (1960), ISSN 0003-9950, Vol. 126, no 1, p. 51-57Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To characterize the clinical phenotype and to study the course of disease in patients with Alström syndrome, with an emphasis on retinal function assessed with full-field electroretinography (ERG). METHODS: Three age- and sex-matched patients with Alström syndrome were selected from our retinitis pigmentosa register for repeated ophthalmologic examinations that included tests for color vision and visual fields using Goldmann perimetry and for repeated assessment of full-field ERGs. RESULTS: Electroretinography demonstrated cone-rod degeneration in all 3 patients. A concomitant impairment of color vision and visual fields was also observed as well as marked variation in retinal function and in disease severity. CONCLUSIONS: Full-field ERGs confirmed that Alström syndrome is associated with a cone-rod type of retinal degeneration. In this study, we have shown a striking variability in retinal function and disease onset and severity, which has, to our knowledge, not been described previously in Alström syndrome.

  • 32.
    Mollazadegan, Kaziwe
    et al.
    Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Kugelberg, Maria
    St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
    Tallstedt, Leif
    St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Increased risk of uveitis in coeliac disease: a nationwide cohort study2012In: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079, Vol. 96, no 6, p. 857-861Article in journal (Refereed)
    Abstract [en]

    Background: Case reports suggest a potential association between coeliac disease (CD) and uveitis, but larger well-controlled studies are lacking. The aim of this study was therefore to examine the risk of uveitis in patients with biopsy-verified CD.

    Methods: Small intestinal biopsy reports performed between July 1969 and February 2008 were collected from all (n-28) pathology departments in Sweden. From these reports, 29 044 patients with CD (equals villous atrophy, Marsh 3) were identified. Uveitis was defined according to relevant International Classification of Disease codes in the Swedish National Patient Register. Cox regression was used to estimate HR for uveitis in individuals with CD compared with those in reference individuals matched for age, sex, county and calendar year.

    Results: During follow-up, 148 patients with CD developed uveitis (expected count 112), corresponding to a HR of 1.32 (95% CI 1.10 to 1.58). The absolute risk of uveitis was 50/100 000 person-years in CD. The risk estimate did not change more than marginally when adjusted for type 1 diabetes, rheumatoid arthritis and autoimmune thyroid disease (HR 1.30; 95% CI 1.08 to 1.56). The risk of uveitis remained significantly increased even 5 years after CD diagnosis (HR 1.31; 95% CI 1.04 to 1.64).

    Conclusion: A moderately increased risk of uveitis was found in patients with biopsy- verified CD. CD might be considered in patients with uveitis of unknown aetiology.

  • 33.
    Mollick, Tanzina
    et al.
    Örebro University, School of Medical Sciences.
    Mohlin, Camilla
    Department of Chemistry and Biomedicine, Linnaeus University, Kalmar, Sweden.
    Johansson, Kjell
    Örebro University, School of Medical Sciences.
    Human neural progenitor cells decrease photoreceptor degeneration, normalize opsin distribution and support synapse structure in cultured porcine retina2016In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1646, p. 522-534Article in journal (Refereed)
    Abstract [en]

    Retinal neurodegenerative disorders like retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy and retinal detachment decrease retinal functionality leading to visual impairment. The pathological events are characterized by photoreceptor degeneration, synaptic disassembly, remodeling of postsynaptic neurons and activation of glial cells. Despite intense research, no effective treatment has been found for these disorders. The current study explores the potential of human neural progenitor cell (hNPC) derived factors to slow the degenerative processes in adult porcine retinal explants. Retinas were cultured for 3 days with or without hNPCs as a feeder layer and investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), immunohistochemical, western blot and quantitative real time-polymerase chain reaction (qRT-PCR) techniques. TUNEL showed that hNPCs had the capacity to limit photoreceptor cell death. Among cone photoreceptors, hNPC coculture resulted in better maintenance of cone outer segments and reduced opsin mislocalization. Additionally, maintained synaptic structural integrity and preservation of second order calbindin positive horizontal cells was also observed. However, Müller cell gliosis only seemed to be alleviated in terms of reduced Müller cell density. Our observations indicate that at 3 days of coculture, hNPC derived factors had the capacity to protect photoreceptors, maintain synaptic integrity and support horizontal cell survival. Human neural progenitor cell applied treatment modalities may be an effective strategy to help maintain retinal functionality in neurodegenerative pathologies. Whether hNPCs can independently hinder Müller cell gliosis by utilizing higher concentrations or by combination with other pharmacological agents still needs to be determined.

  • 34.
    Morén, Åsa
    et al.
    Department of Ophthalmology, Västmanland County Hospital, Västerås, Sweden.
    Sundbom, Magnus
    Department of Surgical Sciences, Upper Gastrointestinal Surgery, Uppsala University, Uppsala, Sweden.
    Ottosson, Johan
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    Granstam, Elisabet
    Department of Ophthalmology, Västmanland County Hospital, Västerås, Sweden; Center for Clinical Research, Uppsala University/County Council of Västmanland, Västerås, Sweden.
    Gastric bypass surgery does not increase the risk for sight-threatening diabetic retinopathy2018In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 96, no 3, p. 279-282Article in journal (Refereed)
    Abstract [en]

    Purpose: To study the occurrence and level of diabetic retinopathy (DRP) before and after planned bariatric surgery and to investigate potential risk factors for deterioration of DRP.

    Methods: The Scandinavian Obesity Surgery Registry (SOReg) was used to identify diabetic patients who underwent gastric bypass (GBP) surgery at three centres in Sweden during 2008-2010. Information regarding DRP screening was obtained from ophthalmological patient charts. Patients who had DRP screening before and after GBP surgery were included in the study.

    Results: The survey included 117 patients. Mean age was 50 (SD 10) years, body mass index (BMI) 43 (SD 8) kg/m(2) and HbA1c 64 (SD 18) mmol/mol before surgery. One year post-GBP, BMI was reduced to 31 (SD 6) kg/m(2). HbA1c was 43 (SD 10) mmol/mol, and in 66% (77/117) treatment for diabetes had been discontinued. Occurrence of DRP before GBP was as follows: no DRP 62%, mild 26%, moderate 10%, severe 0% and proliferative DRP 2%. No significant changes in occurrence of DRP after surgery were observed. Twelve patients (16%) developed mild DRP. In seven patients with pre-existing DRP, deterioration was observed and two of these patients required treatment for sight-threatening DRP. No association between preoperative BMI, HbA1c or reduction in HbA1c and worsening of DRP was found.

    Conclusion: In a majority of patients, no deterioration of DRP following GBP was observed. Screening for DRP before planned surgery is recommended for all diabetic patients about to undergo bariatric surgery to identify any pre-existing DRP.

  • 35.
    Olafsdottir, Eydis
    et al.
    Department of Ophthalmology, The National University Hospital, Reykjavik, Iceland; University of Iceland, Reykjavik, Iceland; Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Andersson, Dan K G
    Family Medicine and Preventive Medicine Section, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    Dedorsson, Inger
    Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Svärdsudd, Kurt
    Family Medicine and Preventive Medicine Section, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    Jansson, Stefan P O
    Örebro University, School of Medical Sciences. Family Medicine and Preventive Medicine Section, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden; Family Medicine Research Centre, Örebro County Council, Örebro, Sweden.
    Stefánsson, Einar
    Department of Ophthalmology, The National University Hospital, Reykjavik, Iceland; University of Iceland, Reykjavik, Iceland.
    Early detection of type 2 diabetes mellitus and screening for retinopathy are associated with reduced prevalence and severity of retinopathy2016In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 94, no 3, p. 232-239Article in journal (Refereed)
    Abstract [en]

    Purpose: To explore whether the prevalence and severity of retinopathy differ in diabetes cohorts diagnosed through screening as compared with conventional health care.

    Methods: A total of 257 diabetes patients, 151 detected through screening and 106 through conventional clinical care, were included. Retinopathy was evaluated by fundus photography. The modified Airlie House adaptation of the Early Treatment Retinopathy Study protocol was used to grade the photographs. Averages of clinically collected fasting blood glucose (FBG), blood pressure and body mass index values were compiled from diabetes diagnosis until the eye examination. Blood chemistry, smoking habits and peripheral neuropathy were assessed at the time of the eye examination.

    Results: Among the screening-detected patients, 22% had retinopathy as compared to 51% among those clinically detected (p < 0.0001). In a multivariate analysis, patients with retinopathy were more likely to have increased average FBG (OR 1.42, 95% CI 1.19-1.70 per mmol/l) and peripheral neuropathy (OR 2.75, 95% CI 1.40-5.43), but less likely to have screening-detected diabetes (OR 0.31, 95% CI 0.17-0.57). Similar results were found using increasing severity grade of retinopathy as outcome. The cumulative retinopathy prevalence for the screening-detected diabetes cohort as compared with the clinically diagnosed cohort was significantly lower from 10 years' follow-up and onwards (p = 0.0002).

    Conclusions: Among patients with screening-detected diabetes, the prevalence of retinopathy and increasing severity of retinopathy were significantly lower than among those who had their diabetes diagnosed through conventional care, even when other risk factors for retinopathy such as duration, hyperglycaemia and blood pressure were considered. Early detection of diabetes reduces prediagnostic time spent with hyperglycaemia. In combination with early and regular screening for retinopathy, more effective prevention against retinopathy can be provided.

  • 36.
    Polinati, P. P.
    et al.
    Research Program of Molecular Neurology, Biomedicum 1, University of Helsinki, Helsinki, Finland.
    Ilmarinen, T.
    Institute of Biomedical Technology, University of Tampere, Tampere, Finland; BioMediTech, Tampere, Finland.
    Trokovic, R.
    Research Program of Molecular Neurology, Biomedicum 1, University of Helsinki, Helsinki, Finland.
    Hyötyläinen, Tuulia
    Valtion Teknillinen Tutkimuskeskus (VTT) Technical Research Centre of Finland, Espoo, Finland.
    Otonkoski, T.
    Research Program of Molecular Neurology, Biomedicum 1, University of Helsinki, Helsinki, Finland; Children’s Hospital, Helsinki University Central Hospital, Helsinki, Finland.
    Suomalainen, A.
    Research Program of Molecular Neurology, Biomedicum 1, University of Helsinki, Helsinki, Finland; Children’s Hospital, Helsinki University Central Hospital, Helsinki, Finland.
    Skottman, H.
    Institute of Biomedical Technology, University of Tampere, Tampere, Finland; BioMediTech, Tampere, Finland.
    Tynitiina, T.
    Research Program of Molecular Neurology, Biomedicum 1, University of Helsinki, Helsinki, Finland; Children’s Hospital, Helsinki University Central Hospital, Helsinki, Finland.
    Patient-specific induced pluripotent stem cell-derived RPE cells: Understanding the pathogenesis of retinopathy in long-chain 3-hydroxyacyl-CoA dehydrogenase deiciency2015In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 56, no 5, p. 3371-3382Article in journal (Refereed)
    Abstract [en]

    Purpose: Retinopathy is an important manifestation of trifunctional protein (TFP) deficiencies but not of other defects of fatty acid oxidation. The common homozygous mutation in the TFP α-subunit gene HADHA (hydroxyacyl-CoA dehydrogenase), c.1528G>C, affects the long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) activity of TFP and blindness in infancy. The pathogenesis of the retinopathy is unknown. This study aimed to utilize human induced pluripotent stem cell (hiPSC) technology to create a disease model for the disorder, and to derive clues for retinopathy pathogenesis.

    Methods: We implemented hiPSC technology to generate LCHAD deficiency (LCHADD) patient-specific retinal pigment epithelial (RPE) monolayers. These patient and control RPEs were extensively characterized for function and structure, as well as for lipid composition by mass spectrometry.

    Results: The hiPSC-derived RPE monolayers of patients and controls were functional, as they both were able to phagocytose the photoreceptor outer segments in vitro. Interestingly, the patient RPEs had intense cytoplasmic neutral lipid accumulation, and lipidomic analysis revealed an increased triglyceride accumulation. Further, patient RPEs were small and irregular in shape, and their tight junctions were disorganized. Their ultrastructure showed decreased pigmentation, few melanosomes, and more melanolysosomes.

    Conclusions: We demonstrate that the RPE cell model reveals novel early pathogenic changes in LCHADD retinopathy, with robust lipid accumulation, inefficient pigmentation that is evident soon after differentiation, and a defect in forming tight junctions inducing apoptosis. We propose that LCHADD-RPEs are an important model for mitochondrial TFP retinopathy, and that their early pathogenic changes contribute to infantile blindness of LCHADD.

  • 37.
    Rantamäki, Antti H.
    et al.
    Department of Ophthalmology, Helsinki Eye Lab, University of Helsinki, Helsinki, Finland.
    Seppänen-Laakso, Tuulikki
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Oresic, Matej
    Örebro University, School of Medical Sciences. VTT Technical Research Centre of Finland, Espoo, Finland.
    Jauhiainen, Matti
    National Institute for Health and Welfare and FIMM Institute for Molecular Medicine Finland, Helsinki, Finland.
    Holopainen, Juha M.
    Department of Ophthalmology, Helsinki Eye Lab, University of Helsinki, Helsinki, Finland.
    Human tear fluid lipidome: from composition to function2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 5, article id e19553Article in journal (Refereed)
    Abstract [en]

    We have explored human aqueous tear fluid lipidome with an emphasis to identify the major lipids. We also address the physiological significance of the lipidome. The tears were analysed using thin layer chromatographic, enzymatic and mass spectrometric techniques. To emphasize the physiological aspect of the lipidome, we modelled the spreading of the non-polar tear fluid lipids at air-water interface in macroscopic scale with olive oil and egg yolk phosphatidylcholine. Based on enzymatic analysis the respective concentrations of choline-containing lipids, triglycerides, and cholesteryl esters were 48±14, 10±0, and 21±18 µM. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry analysis showed that phosphatidylcholine and phosphatidylethanolamine were the two most common polar lipids comprising 88±6% of all identified lipids. Triglycerides were the only non-polar lipids detected in mass spectrometric analysis i.e. no cholesteryl or wax esters were identified. The spreading experiments show that the presence of polar lipids is an absolute necessity for a proper spreading of non-polar tear fluid lipids. We provide evidence that polar lipids are the most common lipid species. Furthermore, we provide a physiological rationale for the observed lipid composition. The results open insights into the functional role of lipids in the tear fluid and also aids in providing new means to understand and treat diseases of the ocular surface.

  • 38.
    Rautiainen, Susanne
    et al.
    Inst Environm Med, Div Nutr Epidemiol, Karolinska Inst, Stockholm, Sweden.
    Lindblad, Birgitta Ejdervik
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Morgenstern, Ralf
    Inst Environm Med, Div Biochem Toxicol, Karolinska Inst, Stockholm, Sweden.
    Wolk, Alicja
    Inst Environm Med, Div Nutr Epidemiol, Karolinska Inst, Stockholm, Sweden.
    Total Antioxidant Capacity of the Diet and Risk of Age-Related Cataract A Population-Based Prospective Cohort of Women2014In: JAMA ophthalmology, ISSN 2168-6165, E-ISSN 2168-6173, Vol. 133, no 3, p. 247-252Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE: To our knowledge, no previous epidemiologic study has investigated the association between all antioxidants in the diet and age-related cataract. The total antioxidant capacity (TAC) concept aims to measure the capacity from all antioxidants in the diet by also taking synergistic effects into account.

    OBJECTIVE: To investigate the association between the TAC of the diet and the incidence of age-related cataract in a population-based prospective cohort of middle-aged and elderly women.

    DESIGN, SETTING, AND PARTICIPANTS: Questionnaire-based nutrition survey within the prospective Swedish Mammography Cohort study, which included 30 607 women (aged 49-83 years) who were observed for age-related cataract incidence for a mean of 7.7 years.

    EXPOSURE: The TAC of the diet was estimated using a database of foods analyzed with the oxygen radical absorbance capacity assay.

    MAIN OUTCOMES AND MEASURES: Information on incident age-related cataract diagnosis and extraction was collected through linkage to registers in the study area.

    RESULTS: There were 4309 incident cases of age-related cataracts during the mean 7.7 years of follow-up (234 371 person-years). The multivariable rate ratio in the highest quintile of the TAC of the diet compared with the lowest was 0.87 (95% CI, 0.79-0.96; P for trend = .03). The main contributors to dietary TAC in the study population were fruit and vegetables (44.3%), whole grains (17.0%), and coffee (15.1%).

    CONCLUSIONS AND RELEVANCE: Dietary TAC was inversely associated with the risk of age-related cataract. Future studies examining all antioxidants in the diet in relation to age-related cataract are needed to confirm or refute our findings.

  • 39.
    Robciuc, A.
    et al.
    Department of Ophthalmology, Helsinki Eye Lab, University of Helsinki, Helsinki, Finland; Public Health Genomic Unit, Biomedicum Helsinki Unit, National Institute for Health and Welfare, Helsinki, Finland.
    Hyötyläinen, Tuulia
    Department of Quantitative Biology and Bioinformatics, VTT Technical Research Centre of Finland, Espoo, Finland.
    Jauhiainen, M.
    Public Health Genomic Unit, Biomedicum Helsinki Unit, National Institute for Health and Welfare, Helsinki, Finland.
    Holopainen, J. M.
    Department of Ophthalmology, Helsinki Eye Lab, University of Helsinki, Helsinki, Finland.
    Ceramides in the pathophysiology of the anterior segment of the eye2013In: Current Eye Research, ISSN 0271-3683, E-ISSN 1460-2202, Vol. 38, no 10, p. 1006-1016Article, review/survey (Refereed)
    Abstract [en]

    Purpose: Sphingolipid (SL) research reached a peak in the past years. Yet this positive trend was not evident for eye research as the relative number of studies centered on SLs is decreasing. Our aim is to encourage the inclusion of SL metabolites in studies of ocular pathophysiology by summarizing recent findings and current awareness concerning ceramides in the anterior segment of the eye.

    Methods: Review of literature relating to ceramides as bioactive lipids and the extent to which their particular nature was investigated in ocular pathophysiology.

    Results: Ceramides are rare but indispensable lipids that influence cellular responses through their effects on membrane biophysical properties or direct interaction with target proteins. Their biological significance is increased by variability and adaptability as there are tens of enzymes designed to modulate their function. The eye offers a set of unique environments where ceramides or other SLs have not been extensively studied. Not surprisingly, ceramides were associated with apoptosis in the metabolically active tissues, while little is known about its effects on the biophysical properties of the tears or lens lipids. More so, there are still aspects of the ocular homeostasis control where SLs contribution has not been investigated to date (e. g. pathogen aggression).

    Conclusions: Ceramides and SL metabolism still receive increasing attention and have proven to be a significant metabolite in many research fields (e. g. cancer, stress response and inflammation) and there are yet many questions that they will aid answer. With the present work, we seek to increase awareness of these lipids also in eye research and to highlight their importance as common regulators of various diseases.

  • 40.
    Sagerfors, Susanna
    et al.
    Örebro University, School of Medical Sciences. Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Lindblad, Birgitta Ejdervik
    Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Infectious keratitis: Isolated microbes and their antibiotic susceptibility pattern during 11 years in Region Örebro County, Sweden2018In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 9, article id 3678Article in journal (Refereed)
  • 41.
    Schulz-Key, Steffen
    et al.
    Department of Ophthalmology, Uppsala University Hospital, Uppsala, Sweden.
    Carlsson, Jan-Olof
    Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Crafoord, Sven
    Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Longterm follow-up of pars plana vitrectomy for vitreous floaters: complications, outcomes and patient satisfaction.2011In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 89, no 2, p. 159-165Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Floaters caused by degenerative or postoperative changes in the vitreous can interfere with all aspects of visual functioning. The aim of this study is to report the longterm outcome of pars plana vitrectomy (PPV) for persistent vitreous opacities.

    METHODS: In a retrospective, non-randomized, interventional case study we reviewed all cases of vitreous floaters that were vitrectomized at our department between 1997 and 2006. Patient complaints and satisfaction were assessed by a questionnaire administered at the end of follow-up.

    RESULTS: Seventy-three consecutive cases were included (61 patients). Mean Snellen best corrected visual acuity (BCVA) before surgery was 0.81. Overall, 85% of patients complained of severe or very severe difficulty caused by floaters. A total of 42% of eyes were pseudophakic, four of which were operated with combined PPV and phacoemulsification. Mean follow-up time was 37 months. Of the phakic eyes, 60% were operated for cataract during follow-up. One retinal detachment (RD) occurred immediately postoperatively (1.3%) and another four eyes developed RD during longterm follow-up 24-44 months after PPV (5.5% of cases). Postoperative BCVA remained mostly unchanged. Overall, 88% of patients were satisfied with the results of the operation.

    CONCLUSIONS: Some patients make considerable complaints as a result of vitreous opacities and their distress does not correlate with visual acuity. Vitrectomy is a safe and effective procedure with which to help these patients. Patients should be informed about the risk of cataract progression, unexpected inflammatory reaction and an increased risk for RD several years after PPV (5.5%).

  • 42.
    Selin, Jinjin Zheng
    et al.
    Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden .
    Orsini, Nicola
    Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden .
    Lindblad, Birgitta Ejdervik
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden .
    Wolk, Alicja
    Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden .
    Long-term physical activity and risk of age-related cataract: a population-based prospective study of male and female cohorts2015In: Ophthalmology (Rochester, Minn.), ISSN 0161-6420, E-ISSN 1549-4713, Vol. 122, no 2, p. 274-280Article in journal (Refereed)
    Abstract [en]

    Objective: To examine the association of total and specific types of physical activity, including walking or bicycling, exercising, work or occupational activity, home or housework, and leisure time inactivity with the risk of age-related cataract in women and men.

    Design: Population-based prospective cohort study.

    Participants: A total of 52 660 participants (23 853 women and 28 807 men) 45 to 83 years of age from the Swedish Mammography Cohort and the Cohort of Swedish Men.

    Methods: Physical activity was assessed using a self-administered questionnaire at baseline. Cataract diagnosis and extraction were identified through linkage to registers.

    Main Outcome Measures: Incident age-related cataract diagnosis and cataract extraction.

    Results: During a mean 12.1 years of follow-up (between January 1, 1998, and December 31, 2011; 634 631 person-years), 11 580 incident age-related cataract cases were identified. After adjusting for potential con-founders, the highest quartile of total physical activity was statistically significantly associated with 13% decreased risk of cataract compared with the lowest (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.82-0.92). Walking or bicycling (>60 minutes/day vs. hardly ever; HR, 0.88; 95% CI, 0.82-0.95) and work or occupational activity (heavy manual labor vs. mostly sitting; HR, 0.84; 95% CI, 0.78-0.91) also were associated with decreased risk of cataract. Exercise training and home or housework were not associated with cataract risk. Leisure time inactivity was associated with increased risk of cataract (>6 vs. <1 hours/day; HR, 1.27; 95% CI, 1.07-1.50). The HR for high long-term total physical activity compared with low levels both at 30 years of age and at baseline was 0.76 (95% CI, 0.69-0.85).

    Conclusions: Our findings indicate that high total physical activity, especially in the long term, and such specific types of physical activity as walking or bicycling and work or occupational activity, may be associated with decreased risk of age-related cataract. Conversely, high inactivity levels may be associated with increased risk of cataract.

  • 43.
    Sharif, A.
    et al.
    City Council Värmland, Dept Ophthalmol, Karlstad, Sweden..
    Jendle, Johan
    Örebro University, School of Medical Sciences.
    Hellgren, K. J.
    Cty Council Varmland, Dept Ophthalmol, Karlstad, Sweden..
    Compliance to Screening of Diabetic Retinopathy with 18 to 36 Months Interval2018In: European Journal of Ophthalmology, ISSN 1120-6721, E-ISSN 1724-6016, Vol. 28, no Suppl. 1, p. 9-9Article in journal (Other academic)
  • 44.
    Slidsborg, Carina
    et al.
    Department of Ophthalmology, Copenhagen University Hospital, Glostrup Hospital, Glostrup, Denmark.
    Lyng Forman, Julie
    Departmant of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
    Fielder, Alistair R.
    Department of Optometry and Visual Science, City University, London, UK .
    Crafoord, Sven
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden.
    Baggesen, Kirsten
    Department of Ophthalmology, Aalborg University Hospital, Aalborg, Denmark .
    Bangsgaard, Regitze
    Department of Ophthalmology, Copenhagen University Hospital, Glostrup Hospital, Glostrup, Denmark.
    Callo Fledelius, Hans
    Department of Ophthalmology, Copenhagen University Hospital, Glostrup Hospital, Glostrup, Denmark.
    Greisen, Gorm
    Department of Neonatology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
    La Cour, Morten
    Department of Ophthalmology, Copenhagen University Hospital, Glostrup Hospital, Glostrup, Denmark.
    Experts do not agree when to treat retinopathy of prematurity based on plus disease2012In: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079, Vol. 96, no 4, p. 549-553Article in journal (Refereed)
    Abstract [en]

    Objectives: To investigate inter-reader agreement on five severity levels of central vascular changes (none, mild, moderate, severe pre-plus disease, plus disease) and aggressive posterior retinopathy of prematurity (ROP), and to see whether an unintended shift in indication for treatment occurred.

    Methods: Four international ROP readers participated. Before the grading of the photographs, the readers were informed that a high proportion of advanced ROP cases were included. In total, 243 photographs/948 quadrants were available from 136 infants. As a standard series of photographs was available, grading was performed under optimised conditions.

    Results: The four readers agreed on the quadrant scores of only 70 (7.38%) of the 948 quadrants-that is, on 1, 5, 15, 4 and 45 quadrants for scores 0, 1, 2, 3 and 4, respectively. The mean scores differed systematically between the readers (permutation test, p<0.0001). Agreement on presence of aggressive posterior ROP from all four readers was not obtained for any of the photographs. Readers scored plus disease in at least two quadrants in 95.5% of the eyes for which treatment was indicated. All four readers agreed on the scoring of indication for treatment for 195 eyes (80.2%); however, treatment was only recommended in 18 (7.4%) eyes. One reader was found to differ systematically from the others in indicating treatment (Rasch analysis; p=0.0001). Finally, a significant shift in indication for treatment occurred between birth period 2000-2002 and 2003-2006 (Mann-Whitney rank sum test, p<0.001).

    Conclusions: Inter-reader agreement on central vascular changes is poor, especially when based on more than two rating categories. The subjective nature of diagnosing such vascular changes possibly resulted in earlier treatment of preterm infants in Denmark over the entire study period (1997-2006). The recent increased incidence of treated infants in Denmark is, at least in part, explained by a significant shift in indication for treatment.

  • 45.
    Wahlqvist, Moa
    et al.
    Örebro University, School of Health Sciences.
    Möller, Kerstin
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Möller, Claes
    Örebro University, School of Health Sciences.
    Danermark, Berth
    Örebro University, School of Health Sciences.
    Physical and psychological health, social trust and financial situation for persons with Usher syndrome type 12016In: The British Journal of Visual Impairment, ISSN 0264-6196, E-ISSN 1744-5809, Vol. 34, no 1, p. 15-25Article in journal (Refereed)
    Abstract [en]

    The article describes physical health, psychological health, social trust, and financial situation in persons with deafblindness due to Usher syndrome type 1 (USH1) in comparison with a crosssection of the Swedish population. Persons with USH1 were recruited through the Swedish Usher database. Totally, 87 adults received the Health on Equal Terms (HET) questionnaire. The HET was adjusted, thus the questions were translated into Swedish sign language, and a large font size, better contrast, and a structure compatible with the Braille script reader were also provided. The questionnaire comprises a wide range of domains related to health and wellbeing. In all, 60 persons responded (60% women, mean age: 49 years, range: 21–79 years). The persons with USH1 were compared to a cross section of the Swedish population that included 5738 individuals (56% women, mean age: 49 years, range: 16–84 years). Significant differences in physical health, psychological health, social trust, and financial situation as well as the odds ratio adjusted for sex and age, and its 95% confidence interval are reported. The psychological health, social trust, and financial situation of persons with USH1 were significantly poorer compared to the reference group although this was not the case for physical health. Persons with USH1 only expressed significantly more problems with headache compared to the cross section of the Swedish population. The respondents revealed major problems with fatigue, loss of confidence, and suicide thoughts and attempts. Major social trust and financial problems were reported in terms of refraining going out alone, not receiving help, having no one with whom to share thoughts, and confide in and being unable to obtain 15.000 SEK (approximately US$1.724 or €1.544) in the case of an unforeseen situation. To identify factors associated with physical health, psychological health, social trust, and financial situation is important in the design of future rehabilitation strategies for persons with USH1. The high level of psychological distress and lack of social trust reported could be related to ontological insecurity, as well as lack of recognition from others. Special attention must be devoted to suicide behavior.

  • 46.
    Zetterlund, Christina
    et al.
    Örebro University, School of Health and Medical Sciences.
    Lundqvist, Lars-Olov
    Richter, Hans O.
    The relationship between low vision and musculoskeletal complaints: a case control study between age-related macular degeneration patients and age-matched controls with normal vision2009In: Journal of optometry, ISSN 1989-1342, Vol. 2, no 3, p. 127-133Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Age-related Macular Degeneration (ARMD) patients often describe complaints from neck and scapula area muscles and a decreased postural control. In clinical assessment, these complaints are considered to be due to old age.PURPOSE: This study focuses on low-vision patients with ARMD, comparing them to age-matched controls without any eye disease, in order to evaluate if the linkage between self-rated visual complaints and musculoskeletal complaints is more prominent when low vision is present.METHODS: In a cross-sectional study, 24 ARMD patients, aged 65 to 85, were compared to a group of 24 controls without visual problems having a similar age distribution. Visual acuity, the need for magnification plus other optical and visual parameters were assessed. Visual, musculoskeletal and balance/proprioceptive complaints were collected by means of a self-rating questionnaire. The Visual Functioning Questionnaire - Near Activities Subscale (VFQ–NAS) was used to evaluate visual function and related complaints.RESULTS: The correlation between visual complaints and musculoskeletal complaints yielded significant values of the correlation coefficient when performed separately within each group, as well as when calculated on the entire data set [ARMD, Spearman’s rho (ρ)=0.60, P=0.002; control group ρ=0.59, P=0.004; both groups together ρ=0.50 P<0.001]. Stepwise multiple regression analysis supported the hypothesized effect of vision (Visual complaints + Minimum readable typefaces) on musculoskeletal complaints, (r2=0.42, P<0.05). CONCLUSIONS: The results in this study support the hypothesis that a relationship exists between visual and musculoskeletal problems.

  • 47.
    Zetterlund, Christina
    et al.
    Örebro University, School of Medical Sciences. The Low Vision Centre, Region Örebro County, Örebro, Sweden; .
    Richter, Hans Olof
    Centre for Musculoskeletal Research, Department of Occupational and Public Health Sciences, Faculty of Health and Occupational Studies, University of Gävle, Gävle, Sweden.
    Lundqvist, Lars-Olov
    Örebro University, School of Law, Psychology and Social Work. University Health Care Research Center, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Visual, Musculoskeletal, and Balance Complaints in AMD: A Follow-Up Study2016In: Journal of Ophthalmology, ISSN 2090-004X, E-ISSN 2090-0058, article id 2707102Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate whether patients with age-related macular degeneration (AMD) run a potentially higher risk of developing visual, musculoskeletal, and balance complaints than age-matched controls with normal vision.

    Methods: Visual assessments, self-rated visual function, self-rated visual, musculoskeletal, and balance complaints, and perceived general health were obtained in 37 AMD patients and 18 controls, at baseline and after an average of 3.8 years later.

    Results: At follow-up both groups reported decreased visual acuity (VA) and visual function, but only AMD patients reported significantly increased visual, musculoskeletal, and balance complaints. Decreased VA, need for larger font size when reading, need for larger magnification, and decreased self-rated visual function were identified as risk markers for increased complaints in AMD patients. These complaints were also identified as risk markers for decreased health. For controls, decreased VA and self-reported visual function were associated with increased visual and balance complaints.

    Conclusions: Visual deterioration was a risk marker for increased visual, musculoskeletal, balance, and health complaints in AMD patients. Specifically, magnifying visual aids, such as CCTV, were a risk marker for increased complaints in AMD patients. This calls for early and coordinated actions to treat and prevent visual, musculoskeletal, balance, and health complaints in AMD patients.

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