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  • 251.
    Ristoff, E
    et al.
    Karolinska institutet, Stockholm.
    Burstedt, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Larsson, A
    Wachtmeister, Lillemor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Progressive retinal dystrophy in two sisters with glutathione synthetase (GS) deficiency2007In: J Inherit Metab Dis, Vol. 30, no 1, p. 102-Article in journal (Refereed)
    Abstract [en]

    We report the ophthalmological findings of two sisters with severe glutathione synthetase deficiency, an autosomal recessive inborn error of metabolism resulting in very low intracellular levels of the free-radical scavenger glutathione. The patients were investigated because of declining visual acuity. The most prominent finding was progressive retinal dystrophy with hyperpigmentations and maculopathy. Generally disturbed functioning of both the outer and inner layers of the retina resulted in attenuated or nearly abolished electroretinograms. These findings agree with a rod/cone type of retinal dystrophy, and we suggest that this is due to glutathione deficiency. Treatment with antioxidants such as vitamins E and C seems to prevent the progression of CNS damage. We speculate that it might also prevent retinal dystrophy in patients with glutathione synthetase deficiency. We suggest that patients with retinal dystrophy and additional neurological signs should be investigated for a defect in glutathione metabolism. Also, we recommend that patients with low levels of glutathione should be examined for retinal dystrophy. Our results suggest that a decreased capacity for scavenging reactive oxygen species and/or increased oxidative stress may cause retinal dystrophy. If this is the case, the redox state in the retina should be a potentially useful therapeutic target to prevent reduced visual function and blindness.

  • 252. Rodrigues, Ian A.
    et al.
    Sprinkhuizen, Sara M.
    Barthelmes, Daniel
    Blumenkranz, Mark
    Cheung, Gemmy
    Haller, Julia
    Johnston, Robert
    Kim, Ramasamy
    Klaver, Caroline
    Mckibbin, Martin
    Ngah, Nor Fariza
    Pershing, Suzann
    Shankar, Dato
    Tamura, Hiroshi
    Tufail, Adnan
    Weng, Christina Y.
    Westborg, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Registercenter Syd/EyeNet Sweden, Karlskrona, Sweden.
    Yelf, Catherine
    Yoshimura, Nagahisa
    Gillies, Mark C.
    Defining a Minimum Set of Standardized Patient-centered Outcome Measures for Macular Degeneration2016In: American Journal of Ophthalmology, ISSN 0002-9394, E-ISSN 1879-1891, Vol. 168, p. 1-12Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To define a minimum set of outcome measures for tracking, comparing, and improving macular degeneration care.

    DESIGN: Recommendations from a working group of international experts in macular degeneration outcomes registry development and patient advocates, facilitated by the International Consortium for Health Outcomes Measurement (ICHOM).

    METHODS: Modified Delphi technique, supported by structured teleconferences, followed by online surveys to drive consensus decisions. Potential outcomes were identified through literature review of outcomes collected in existing registries and reported in major clinical trials. Outcomes were refined by the working group and selected based on impact on patients, relationship to good clinical care, and feasibility of measurement in routine clinical practice.

  • 253.
    Rodríguez, Maria Angels
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Liu, Jing-Xia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Parkkonen, Kimmo
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Li, Zhenlin
    Domellöf, Fatima Pedrosa
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    The Cytoskeleton in the Extraocular Muscles of Desmin Knockout Mice2018In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 12, p. 4847-4855Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the effect of absence of desmin on the extraocular muscles (EOMs) with focus on the structure and composition of the cytoskeleton.

    Methods: The distribution of synemin, syncoilin, plectin, nestin, and dystrophin was evaluated on cross and longitudinal sections of EOMs and limb muscles from 1-year-old desmin knockout mice (desmin−/−) by immunofluorescence. General morphology was evaluated with hematoxylin and eosin while mitochondrial content and distribution were evaluated by succinate dehydrogenase (SDH) and modified Gomori trichrome stainings.

    Results: The muscle fibers of the EOMs in desmin−/− mice were remarkably well preserved in contrast to those in the severely affected soleus and the slightly affected gastrocnemius muscles. There were no signs of muscular pathology in the EOMs and all cytoskeletal proteins studied showed a correct location at sarcolemma and Z-discs. However, an increase of SDH staining and mitochondrial aggregates under the sarcolemma was detected.

    Conclusions: The structure of the EOMs was well preserved in the absence of desmin. We suggest that desmin is not necessary for correct synemin, syncoilin, plectin, and dystrophin location on the cytoskeleton of EOMs. However, it is needed to maintain an appropriate mitochondrial distribution in both EOMs and limb muscles.

  • 254.
    Rodríguez, Maria Angels
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Sandgren Hochhard, Karin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Vicente, André
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Liu, Jing-Xia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Domellöf, Fatima Pedrosa
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Gene expression profile of extraocular muscles following resection strabismus surgery2019In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 182, p. 182-193Article in journal (Refereed)
    Abstract [en]

    This paper aims to identify key biological processes triggered by resection surgery in the extraocular muscles (EOMs) of a rabbit model of strabismus surgery by studying changes in gene expression. Resection surgery was performed in the superior rectus of 16 rabbits and a group of non-operated rabbits served as control. Muscle samples were collected from groups of four animals 1, 2, 4 and 6 weeks after surgery and processed for RNA-sequencing and immunohistochemistry. We identified a total of 164; 136; 64 and 12 differentially expressed genes 1, 2, 4 and 6 weeks after surgery. Gene Ontology enrichment analysis revealed that differentially expressed genes were involved in biological pathways related to metabolism, response to stimulus mainly related with regulation of immune response, cell cycle and extracellular matrix. A complementary pathway analysis and network analysis performed with Ingenuity Pathway Analysis tool corroborated and completed these findings. Collagen I, fibronectin and versican, evaluated by immunofluorescence, showed that changes at the gene expression level resulted in variation at the protein level. Tenascin-C staining in resected muscles demonstrated the formation of new tendon and myotendinous junctions. These data provide new insights about the biological response of the EOMs to resection surgery and may form the basis for future strategies to improve the outcome of strabismus surgery.

  • 255.
    Roux, Sandrine Le
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Borbely, Gabor
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Słoniecka, Marta
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Backman, Ludvig J
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Transforming Growth Factor Beta 1 Modulates the Functional Expression of the Neurokinin-1 Receptor in Human Keratocytes2016In: Current Eye Research, ISSN 0271-3683, E-ISSN 1460-2202, Vol. 41, no 8, p. 1035-1043Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Transforming growth factor beta 1 (TGF-β1) is a cytokine involved in a variety of processes, such as differentiation of fibroblasts into myofibroblasts. TGF-β1 has also been shown to delay the internalization of the neurokinin-1 receptor (NK-1 R) after its activation by its ligand, the neuropeptide substance P (SP). NK-1 R comprises two naturally occurring variants, a full-length and a truncated form, triggering different cellular responses. SP has been shown to affect important events in the cornea - such as stimulating epithelial cell proliferation - processes that are involved in corneal wound healing and thus in maintaining the transparency of the corneal stroma. An impaired signaling through NK-1 R could thus impact the visual quality. We hypothesize that TGF-β1 modulates the expression pattern of NK-1 R in human corneal stroma cells, keratocytes. The purpose of this study was to test that hypothesis.

    METHODS: Cultures of primary keratocytes were set up with cells derived from healthy human corneas, obtained from donated transplantation graft leftovers, and characterized by immunocytochemistry and Western blot. Immunocytochemistry for TGF-β receptors and NK-1 R was performed. Gene expression was assessed with real-time polymerase chain reaction (qPCR).

    RESULTS: Expression of TGF-β receptors was confirmed in keratocytes in vitro. Treating the cells with TGF-β1 significantly reduced the gene expression of NK-1 R. Furthermore, immunocytochemistry for NK-1 R demonstrated that it is specifically the expression of the full-length isotype of the receptor that is reduced after treatment with TGF-β1, which was also confirmed with qPCR using a specific probe for the full-length receptor.

    CONCLUSIONS: TGF-β1 down-regulates the gene expression of the full-length variant of NK-1 R in human keratocytes, which might impact its signaling pathway and thus explain the known delay in internalization after activation by SP seen with TGF-β1 treatment.

  • 256.
    Rydström, Elin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Westin, Oscar
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Koskela, Timo
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Posterior corneal astigmatism in refractive lens exchange surgery2016In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 94, no 3, p. 295-300Article in journal (Refereed)
    Abstract [en]

    Purpose: To assess the anterior, posterior and total corneal spherical and astigmatic powers in patients undergoing refractive lens exchange (RLE) surgery.

    Methods: In 402 consecutive patients planned for RLE at Koskelas Eye Clinic, Luleå, Sweden, right eye data from pre- and postoperative subjective refraction, preoperative IOLMaster® biometry and Pentacam HR® measurements were collected. Postoperative Pentacam HR® data were collected for 54 of the patients. The spherical and astigmatic powers of the anterior and posterior corneal surfaces and for the total cornea were assessed and compared, and surgically, induced astigmatism was calculated using vector analysis.

    Results: The spherical power of the anterior corneal surface was 48.18 ± 1.69D with an astigmatic power of 0.83 ± 0.54D. The corresponding values for the posterior surface were −6.05 ± 2,52D and 0.26 ± 0.15D, respectively. The total corneal spherical power calculated with ray tracing was 42.47 ± 2.89D with a 0.72 ± 0.48D astigmatic power, and the corresponding figures obtained by estimating the posterior corneal surface were 43.25 ± 1.51D (p < 0.001) with a 0.75 ± 0.49D astigmatic power (p = 0.003). In eyes with anterior astigmatism with-the-rule, the total corneal astigmatism is overestimated if the posterior corneal surface is estimated; in eyes, with against-the-rule astigmatism it is underestimated. Had the posterior corneal surface been measured in this material, 14.7% of the patients would have received a spheric instead of a toric IOL, or vice versa.

    Conclusion: Estimating the posterior corneal surface in RLE patients leads to systematic measurement errors that can be reduced by measuring the posterior surface. Such an approach can potentially increase the refractive outcome accuracy in RLE surgery.

  • 257. Rønbeck, Margrethe
    et al.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Taube, Mikaela
    Koivula, Annemari
    Kugelberg, Maria
    Comparison of glistenings in intraocular lenses with three different materials: 12-year follow-up2013In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 91, no 1, p. 66-70Article in journal (Refereed)
    Abstract [en]

    Purpose:  To compare the degree of lens glistenings associated with three intraocular lenses (IOLs) of different materials and examine the relationship between the dioptric power of the optics and lens glistenings in a long-term study. Setting:  St. Erik Eye Hospital, Stockholm, Sweden. Methods:  Forty-six eyes of 46 patients underwent standard phacoemulsification and implantation with a heparin-surface-modified (HSM) polymethylmethacrylate (PMMA) IOL, a silicone IOL or a hydrophobic acrylic IOL. Evaluations of the patients and the glistenings were conducted 11.3-13.4 years postoperatively. The glistenings were examined using Scheimpflug imaging and subsequently analysed using an image analysis program. Results:  The median follow-up time was 12.2 years (range, 11.3-13.4). The hydrophobic acrylic IOL had significantly more lens glistenings than the silicone (p = 0.003) and the PMMA (p = 0.000) IOLs. The silicone IOL had significantly more lens glistenings than the PMMA lens (p = 0.048). The IOL power did not affect the degree of lens glistenings in the hydrophobic acrylic IOL group (p = 0.64). The other groups had too little lens glistenings to evaluate the relationship. Conclusion:  In this long-term follow-up study, the hydrophobic acrylic IOL had a significantly higher degree of lens glistenings compared to the silicone and PMMA IOLs. The PMMA IOL had almost no lens glistenings. The IOL dioptric power was not significantly correlated with the degree of lens glistenings associated with the hydrophobic acrylic IOL.

  • 258.
    Sandgren, Ola
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Kjellgren, Daniel
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ocular manifestations in liver transplant recipients with familial amyloid polyneuropathy.2008In: Acta ophthalmologica, ISSN 1755-3768, Vol. 86, no 5, p. 520-4Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate postoperative ocular involvement in Swedish liver transplant (LT) recipients with familial amyloid polyneuropathy (FAP). METHODS: Routine ophthalmological examinations were performed in 48 LT recipients, with particular attention given to amyloid deposition in the anterior segment and the vitreous body. Medical records were scrutinized for information regarding neurological impairment at the time of the LT. The diagnosis was secured in all cases by examining for amyloid deposits in biopsy specimens and positive genetic testing for amyloidogenic transthyretin (ATTR) Val30Met mutation. RESULTS: Six patients (12.5%) developed vitreous opacities within the post-LT observation period. The first opacities were seen 40 months after transplantation, 8 years after the onset of systemic disease. Four patients (8%) developed secondary glaucoma, the first of which was observed 18 months after the procedure and 6.5 years after the onset of disease. Sixteen patients (33%) developed deposits on the anterior surface of the lens. Scalloped pupillary margins were noted in 10 patients (21%). CONCLUSION: The prevalence of eye complications increases with time after LT and regular follow-up is necessary, especially to disclose the development of glaucoma--a complication with insidious symptoms of which patients are normally unaware.

  • 259.
    Schedin, Staffan
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Hallberg, Per
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Analysis of long-term visual quality with numerical 3D ray tracing after corneal crosslinking treatment2017In: Applied Optics, ISSN 1559-128X, E-ISSN 2155-3165, Vol. 56, no 35, p. 9787-9792Article in journal (Refereed)
    Abstract [en]

    A numerical 3D ray tracing model was used to evaluate the long-term visual effects of two regimens of corneal crosslinking (CXL) treatment of 48 patients with the corneal degeneration keratoconus. The 3D ray tracing analyses were based on corneal elevation data measured by Scheimpflug photography. Twenty-two patients were treated with standard CXL applied uniformly across the corneal surface, whereas 26 patients underwent a customized, refined treatment only at local zones on the cornea (photorefractive intrastromal CXL; PiXL). Spot diagrams, spot root-mean-square (RMS) values, and Strehl ratios were evaluated for the patients prior to and 1, 3, 6, and 12 months after treatment. It was found that the group of patients treated with PiXL, on average, tended to attain a long-term improvement of the corneal optical performance, whereas only minor changes of the optical parameters were found for group treated with standard CXL. Our results confirmed that standard CXL treatment stabilizes the corneal optical quality over time, and thus halts the progression of the corneal degeneration. In addition to stabilization, the results showed that a significantly higher proportion of subjects treated with PiXL improved in RMS, 3, 6, and 12 months after treatment, compared to with CXL (p&lt;0.05). This finding indicates that the PiXL treatment might improve optical quality over time.

  • 260.
    Schedin, Staffan
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Hallberg, Per
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Three-dimensional ray-tracing model for the study of advanced refractive errors in keratoconus2016In: Applied Optics, ISSN 1559-128X, E-ISSN 2155-3165, Vol. 55, no 3, p. 507-514Article in journal (Refereed)
    Abstract [en]

    We propose a numerical three-dimensional (3D) ray-tracing model for the analysis of advanced corneal refractive errors. The 3D modeling was based on measured corneal elevation data by means of Scheimpflug photography. A mathematical description of the measured corneal surfaces from a keratoconus (KC) patient was used for the 3D ray tracing, based on Snell's law of refraction. A model of a commercial intraocular lens (IOL) was included in the analysis. By modifying the posterior IOL surface, it was shown that the imaging quality could be significantly improved. The RMS values were reduced by approximately 50% close to the retina, both for on-and off-axis geometries. The 3D ray-tracing model can constitute a basis for simulation of customized IOLs that are able to correct the advanced, irregular refractive errors in KC.

  • 261. Shulman, Shiri
    et al.
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Stefánsson, Einar
    Loewenstein, Anat
    Rosenblatt, Amir
    Habot-Wilner, Zohar
    Topical dexamethasone-cyclodextrin nanoparticle eye drops for non-infectious Uveitic macular oedema and vitritis: a pilot study2015In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 93, no 5, p. 411-415Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate the safety and efficacy of 1.5% dexamethasone nanoparticle (DexNP) drops in eyes with non-infectious uveitic macular oedema and vitritis. Methods: In a prospective pilot study, DexNP drops were administered four times a day for 4 weeks followed by drops tapering over a period of another 4 weeks. Follow-up time was 12 weeks. Results: Five eyes with macular oedema and three eyes with vitritis were included in the study. Best corrected visual acuity (BCVA) significantly improved from a median of 0.2 logMAR to a median of 0.15 logMAR at 4 weeks' time (p<0.05). Median BCVA was 0.175 logMAR and 0.2 logMAR, at week 8 and 12, respectively (p>0.05). Macular oedema significantly improved at all time-points as compared to baseline (p<0.05) and resolved in all eyes during follow-up. One eye had macular oedema relapse at week 12. Vitritis improved in all eyes and resolved completely in two eyes. One eye had intraocular pressure (IOP) elevation which was well controlled with topical antihypertensive treatment, and one eye had cataract progression. Conclusion: This short pilot study demonstrates favourable effect of 1.5% DexNP eye drops on eyes with non-infectious uveitic macular oedema and vitritis. Further comparative long-term studies are warranted to assess this effect.

  • 262.
    Sjödahl, Rune
    et al.
    Department of Surgery, University Hospital, Linköping.
    Hammarström, Margareta
    Department of Biotechnology, Royal Institute of Technology (KTH), Stockholm.
    Wiklund, Lars
    Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Göteborg.
    Larsson, Lars-Torsten
    Department of Paediatric Surgery, Children's Hospital, Lund.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    [Collective affiliation to the Medical Society is old-fashioned--time for renewal!]2004In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, no 3, p. 218; discussion 219-Article in journal (Other (popular science, discussion, etc.))
  • 263.
    Sjösvärd, Sari
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Fate of donor sclera and late extraocular muscle adaptation after recession2016Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 264. Skiljic, Dragana
    et al.
    Nilsson, Staffan
    Palmer, Mona Seibt
    Tasa, Gunnar
    Juronen, Erkki
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Karlsson, Jan-Olof
    Petersen, Anne
    Zetterberg, Henrik
    Zetterberg, Madeleine
    Estrogen-related Polymorphisms in Estonian Patients with Age-related Cataract2015In: Ophthalmic Genetics, ISSN 1381-6810, E-ISSN 1744-5094, Vol. 36, no 2, p. 188-191Article in journal (Refereed)
  • 265. Skiljic, Dragana
    et al.
    Nilsson, Staffan
    Petersen, Anne
    Karlsson, Jan-Olof
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Kalaboukhova, Lada
    Zetterberg, Madeleine
    Oestradiol levels and superoxide dismutase activity in age-related cataract: a case-control study2016In: BMC Ophthalmology, ISSN 1471-2415, E-ISSN 1471-2415, Vol. 16, article id 210Article in journal (Refereed)
    Abstract [en]

    Background: It has been suggested that the higher prevalence of cataract in women is caused by a withdrawal effect of oestrogen at menopause. In vitro studies have demonstrated protection of serum oestradiol (E2) against oxidative stress through upregulation of antioxidant enzymes, including superoxide dismutase (SOD). The purpose of the present study was to investigate E2 levels and SOD erythrocyte activity in patients with age-related cataract.

    Methods: The studied subjects consisted of 103 patients with age-related cataract and 22 controls. Cataracts were classified as nuclear, cortical, or posterior subcapsular. Blood samples were collected and data on smoking, hormonal use, diabetes and age at menarche/menopause was obtained for all individuals. Serum oestradiol analyses were performed with radioimmunoassay (RIA) and SOD activity was measured in erythrocyte lysates.

    Results: A negative correlation between age and E2 concentration was seen in a linear regression analysis. No correlation was seen between SOD activity and age or gender and no correlation between E2 levels and SOD activity was found using multiple linear regression. The mean level of E2 for all male subjects was 50.1 +/- 16.3 pmol/L, significantly higher compared to 13.8 +/- 11.8 pmol/L for postmenopausal women.

    Conclusion: The present study does not support a role for E2-induced effects on SOD in cataract formation. The findings of higher E2 levels in men than in postmenopausal women may suggest that decreased oestrogen at menopause is partially responsible for the gender-related difference in cataract prevalence. However, the latter can only be verified through prospective randomized trials using hormonal replacement therapy.

  • 266. Skiljic, Dragana
    et al.
    Petersen, Anne
    Karlsson, Jan-Olof
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Nilsson, Staffan
    Zetterberg, Madeleine
    Effects of 17-Estradiol on Activity, Gene and Protein Expression of Superoxide Dismutases in Primary Cultured Human Lens Epithelial Cells2018In: Current Eye Research, ISSN 0271-3683, E-ISSN 1460-2202, Vol. 43, no 5, p. 639-646Article in journal (Refereed)
    Abstract [en]

    Purpose: Protective effects of estradiol against H2O2-induced oxidative stress have been demonstrated in lens epithelial cells. The purpose of this study was to investigate the effects of 17β-estradiol (E2) on the different superoxide dismutase (SOD) isoenzymes, SOD-1, SOD-2, and SOD-3, as well as estrogen receptors (ERs), ERα and ERβ, in primary cultured human lens epithelial cells (HLECs).

    Materials and methods: HLECs were exposed to 0.1 µM or 1 µM E2 for 1.5 h and 24 h after which the effects were studied. Protein expression and immunolocalization of SOD-1, SOD-2, ERα, and ERβ were studied with Western blot and immunocytochemistry. Total SOD activity was measured, and gene expression analyses were performed for SOD1, SOD2, and SOD3.

    Results: Increased SOD activity was seen after 1.5 h exposure to both 0.1 µM and 1 µM E2. There were no significant changes in protein or gene expression of the different SODs. Immunolabeling of SOD-1 was evident in the cytosol and nucleus; whereas, SOD-2 was localized in the mitochondria. Both ERα and ERβ were immunolocalized to the nucleus, and mitochondrial localization of ERβ was evident by colocalization with MitoTracker. Both ERα and ERβ showed altered protein expression levels after exposure to E2.

    Conclusions: The observed increase in SOD activity after exposure to E2 without accompanying increase in gene or protein expression supports a role for E2 in protection against oxidative stress mediated through non-genomic mechanisms.

  • 267.
    Sloniecka, Marta
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Backman, Ludvig J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Antiapoptotic Effect of Acetylcholine in Fas-Induced Apoptosis in Human Keratocytes2016In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, no 14, p. 5892-5902Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To investigate the possible antiapoptotic effect of acetylcholine (ACh) in Fas-mediated apoptosis of primary human keratocytes in vitro, and to explore the underlying mechanism. METHODS. Primary human keratocytes were isolated from healthy corneas. Fas ligand (FasL) was used to induce apoptosis in keratocytes. Cell death was assessed by ELISA. Activity of caspase-3, -7, -8, and -9 was measured with luminescent caspase activity assays. Expression of nuclear factor-kappa B (NF-kappa B) gene was assessed with RT-quantitative (q)PCR. Cytochrome c release apoptosis assay kit was used to extract mitochondria and cytosol. Cytochrome c release, cleavage of Bid, and expression of B-cell lymphoma 2 (Bcl-2) were determined by Western blot. RESULTS. Cell death ELISA revealed that ACh is able to reduce Fas-induced apoptosis in keratocytes. Analysis of the activity of effector caspases-3 and -7 showed that ACh, when added to Fas-treated cells, decreases the activation of both these enzymes. The activity of initiator caspases -8 and -9 also decreased when ACh was added to Fas-treated cells. This antiapoptotic effect of ACh was dependent on ACh concentration and activation of muscarinic ACh receptors. Analysis of the antiapoptotic mechanisms triggered by ACh showed that ACh downregulates expression of FasL-induced NF-kappa B RNA expression, upregulates expression of antiapoptotic protein Bcl-2, downregulates expression of proapoptotic protein Bad, reduces cytochrome c release, and prevents proapoptotic Bid protein cleavage. CONCLUSIONS. Acetylcholine has an antiapoptotic effect in a Fas-apoptosis model of human primary keratocytes in vitro. It is therefore possible that ACh may play a role in corneal wound healing, by modulating its initiation phase.

  • 268.
    Sloniecka, Marta
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Le Roux, Sandrine
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Boman, Peter
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Byström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Zhou, Qingjun
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Qingdao, China.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Expression Profiles of Neuropeptides, Neurotransmitters, and Their Receptors in Human Keratocytes In Vitro and In Situ2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 7, article id e0134157Article in journal (Refereed)
    Abstract [en]

    Keratocytes, the quiescent cells of the corneal stroma, play a crucial role in corneal wound healing. Neuropeptides and neurotransmitters are usually associated with neuronal signaling, but have recently been shown to be produced also by non-neuronal cells and to be involved in many cellular processes. The aim of this study was to assess the endogenous intracellular and secreted levels of the neuropeptides substance P (SP) and neurokinin A (NKA), and of the neurotransmitters acetylcholine (ACh), catecholamines (adrenaline, noradrenaline and dopamine), and glutamate, as well as the expression profiles of their receptors, in human primary keratocytes in vitro and in keratocytes of human corneal tissue sections in situ. Cultured keratocytes expressed genes encoding for SP and NKA, and for catecholamine and glutamate synthesizing enzymes, as well as genes for neuropeptide, adrenergic and ACh (muscarinic) receptors. Keratocytes in culture produced SP, NKA, catecholamines, ACh, and glutamate, and expressed neurokinin-1 and -2 receptors (NK-1R and NK-2R), dopamine receptor D-2, muscarinic ACh receptors, and NDMAR1 glutamate receptor. Human corneal sections expressed SP, NKA, NK-1R, NK-2R, receptor D2, choline acetyl transferase (ChAT), M-3, M4 and M-5 muscarinic ACh receptors, glutamate, and NMDAR1, but not catecholamine synthesizing enzyme or the alpha(1) and beta(2) adrenoreceptors, nor M1 receptor. In addition, expression profiles assumed significant differences between keratocytes from the peripheral cornea as compared to those from the central cornea, as well as differences between keratocytes cultured under various serum concentrations. In conclusion, human keratocytes express an array of neuropeptides and neurotransmitters. The cells furthermore express receptors for neuropeptides/neurotransmitters, which suggests that they are susceptible to stimulation by these substances in the cornea, whether of neuronal or non-neuronal origin. As it has been shown that neuropeptides/neurotransmitters are involved in cell proliferation, migration, and angiogenesis, it is possible that they play a role in corneal wound healing.

  • 269.
    Sloniecka, Marta
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Le Roux, Sandrine
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Zhou, Qingjun
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Qingdao, China.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Substance P Enhances Keratocyte Migration and Neutrophil Recruitment through Interleukin-82016In: Molecular Pharmacology, ISSN 0026-895X, E-ISSN 1521-0111, Vol. 89, no 2, p. 215-225Article in journal (Refereed)
    Abstract [en]

    Keratocytes, the resident cells of the corneal stroma, are responsible for maintaining turnover of this tissue by synthesizing extracellular matrix components. When the cornea is injured, the keratocytes migrate to the wounded site and participate in the stromal wound healing. The neuropeptide substance P (SP), which is also known to be produced by non-neuronal cells, has previously been implicated in epithelial wound healing after corneal injury. Corneal scarring, which occurs in the stroma when the process of wound healing has malfunctioned, is one of the major causes of preventable blindness. This study aimed to elucidate the potential role of SP in keratocyte migration and therefore in stromal wound healing. We report that the expression and secretion of SP in human keratocytes are increased in response to injury in vitro. Moreover, SP enhances the migration of keratocytes by inducing the actin cytoskeleton reorganization and focal adhesion formation through the activation of the phosphatidylinositide 3-kinase and Ras-related C3 botulinum toxin substrate 1/Ras homolog gene family, member A pathway. Furthermore, SP stimulation leads to upregulated expression of the proinflammatory and chemotactic cytokine interleukin-8 (IL-8), which also contributes significantly to SP-enhanced keratocyte migration and is able to attract neutrophils. In addition, the preferred SP receptor, the neurokinin-1 receptor, is necessary to induce keratocyte migration and IL-8 secretion. In conclusion, we describe new mechanisms by which SP enhances migration of keratocytes and recruits neutrophils, two necessary steps in the corneal wound-healing process, which are also likely to occur in other tissue injuries.

  • 270.
    Spang, Christoph
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Backman, Ludvig J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Le Roux, Sandrine
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Chen, Jialin
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Glutamate signaling through the NMDA receptor reduces the expression of scleraxis in plantaris tendon derived cells2017In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 18, article id 218Article in journal (Refereed)
    Abstract [en]

    Background: A body of evidence demonstrating changes to the glutaminergic system in tendinopathy has recently emerged. This hypothesis was further tested by studying the effects of glutamate on the tenocyte phenotype, and the impact of loading and exposure to glucocorticoids on the glutamate signaling machinery.

    Methods: Plantaris tendon tissue and cultured plantaris tendon derived cells were immunohisto-/cytochemically stained for glutamate, N-Methyl-D-Aspartate receptor 1 (NMDAR1) and vesicular glutamate transporter 2 (VGluT2). Primary cells were exposed to glutamate or receptor agonist NMDA. Cell death/viability was measured via LDH/MTS assays, and Western blot for cleaved caspase 3 (c-caspase 3) and cleaved poly (ADP-ribose) polymerase (c-PARP). Scleraxis mRNA (Scx)/protein(SCX) were analyzed by qPCR and Western blot, respectively. A FlexCell system was used to apply cyclic strain. The effect of glucocorticoids was studies by adding dexamethasone (Dex). The mRNA of the glutamate synthesizing enzymes Got1 and Gls, and NMDAR1 protein were measured. Levels of free glutamate were determined by a colorimetric assay.

    Results: Immunoreactions for glutamate, VGluT2, and NMDAR1 were found in tenocytes and peritendinous cells in tissue sections and in cultured cells. Cell death was induced by high concentrations of glutamate but not by NMDA. Scleraxis mRNA/protein was down-regulated in response to NMDA/glutamate stimulation. Cyclic strain increased, and Dex decreased, Gls and Got1 mRNA expression. Free glutamate levels were lower after Dex exposure.

    Conclusions: In conclusion, NMDA receptor stimulation leads to a reduction of scleraxis expression that may be involved in a change of phenotype in tendon cells. Glutamate synthesis is increased in tendon cells in response to strain and decreased by glucocorticoid stimulation. This implies that locally produced glutamate could be involved in the tissue changes observed in tendinopathy.

  • 271.
    Storm, Rickard J
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Persson, David B
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Skalman, Lars Nygård
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Frängsmyr, Lars
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Lindström, Mona
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Rankin, Greg
    Lundmark, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Domellöf, Fatima Pedrosa
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Arnberg, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Human Adenovirus Type 37 Uses αVβ1 and α3β1 Integrins for Infection of Human Corneal Cells2017In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 91, no 5, article id e02019-16Article in journal (Refereed)
    Abstract [en]

    Epidemic keratoconjunctivitis (EKC) is a severe, contagious ocular disease that affects 20 to 40 million individuals worldwide every year. EKC is mainly caused by six types of human adenovirus (HAdV): HAdV-8, -19, -37, -53, -54, and -56. Of these, HAdV-8, -19, and -37 use sialic acid-containing glycans as cellular receptors. αVβ3, αVβ5, and a few additional integrins facilitate entry and endosomal release of other HAdVs. With the exception of a few biochemical analyses indicating that HAdV-37 can interact physically with αVβ5, little is known about the integrins used by EKC-causing HAdVs. Here, we investigated the overall integrin expression on human corneal cells and found expression of α2, α3, α6, αV, β1, and β4 subunits in human corneal in situ epithelium and/or in a human corneal epithelial (HCE) cell line but no or less accessible expression of α4, α5, β3, or β5. We also identified the integrins used by HAdV-37 through a series of binding and infection competition experiments and different biochemical approaches. Together, our data suggest that HAdV-37 uses αVβ1 and α3β1 integrins for infection of human corneal epithelial cells. Furthermore, to confirm the relevance of these integrins in the HAdV-37 life cycle, we developed a corneal multilayer tissue system and found that HAdV-37 infection correlated well with the patterns of αV, α3, and β1 integrin expression. These results provide further insight into the tropism and pathogenesis of EKC-causing HAdVs and may be of importance for future development of new antiviral drugs.IMPORTANCE Keratitis is a hallmark of EKC, which is caused by six HAdV types (HAdV-8, -19, -37, -53, -54, and -56). HAdV-37 and some other HAdV types interact with integrin αVβ5 in order to enter nonocular human cells. In this study, we found that αVβ5 is not expressed on human corneal epithelial cells, thus proposing other host factors mediate corneal infection. Here, we first characterized integrin expression patterns on corneal tissue and corneal cells. Among the integrins identified, competition binding and infection experiments and biochemical assays pointed out αVβ1 and α3β1 to be of importance for HAdV-37 infection of corneal tissue. In the absence of a good animal model for EKC-causing HAdVs, we also developed an in vitro system with multilayer HCE cells and confirmed the relevance of the suggested integrins during HAdV-37 infection.

  • 272. Tavares Ferreira, Joana
    et al.
    Vicente, André
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Proença, Rita
    Santos, Bruno O
    Cunha, João P
    Alves, Marta
    Papoila, Ana L
    Abegão Pinto, Luís
    Choroidal thickness in diabetic patients without diabetic retinopathy2018In: Retina, ISSN 0275-004X, E-ISSN 1539-2864, Vol. 38, no 4, p. 795-804Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To compare choroidal thickness (CT) between diabetic patients without diabetic retinopathy and a nondiabetic group. To explore how CT relates to disease duration, mean arterial pressure, glycemia, glycosylated hemoglobin, intraocular pressure, and ocular pulse amplitude.

    METHODS: Choroidal thickness was assessed using a spectral-domain optical coherence tomography and enhanced depth mode at 13 locations (subfoveal and 3 measurements 500 μm apart in 4 directions-nasal, temporal, superior, and inferior). Linear regression models were used.

    RESULTS: One hundred seventy-five patients were recruited (125 diabetic patients without diabetic retinopathy and 50 nondiabetic patients). In diabetic patients, although without statistical significance, CT showed a trend to be thicker in all locations (6.16-24.27 μm). Choroidal thickness was negatively associated with age (P < 0.001) in both groups, but only in the diabetic group, it was positively associated to ocular pulse amplitude (with a mean increase between 8.5 μm and 11.6 μm for each millimeter of mercury increase in ocular pulse amplitude). Diabetic patients' CT seems to stabilize after 150 months of diabetes, increase with higher glycemia levels (>160 mg/dL) while showing no fluctuation with glycosylated hemoglobin and mean arterial pressure.

    CONCLUSION: There seems to be a thickening of the choroid in diabetic patients without diabetic retinopathy. Moreover, this tissue may be functionally different in diabetes, as the pattern of associations seems to differ between groups.

  • 273.
    Tjust, Anton
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Extraocular Muscles in Amyotrophic Lateral Sclerosis2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease of motor neurons characterized by muscle paralysis and death within 3-5 years of onset. However, due to unknown mechanisms, the extraocular muscles (EOMs) remain remarkably unaffected. The EOMs are highly specialized muscles that differ from other muscles in many respects, including innervation and satellite cells (SCs). Understanding whether these factors play a role in the relative sparing of EOMs in ALS could provide useful clues on how to slow down the progression of ALS in other muscles.

    The EOMs and limb muscles from terminal ALS patients and age-matched controls as well as the commonly used SOD1G93A ALS mouse model were studied with immunofluorescence. Antibodies against neurofilament and synaptophysin were used to identify nerves and neuromuscular junctions (NMJs); against Pax7, NCAM, MyoD, myogenin, Ki-67, dystrophin and laminin, to identify SCs and their progeny in EOMs and limb muscles. The proportion and fiber size of myofibers containing myosin heavy chain (MyHC) slow tonic and MyHC slow twitch were also determined in human EOMs.

    The abundance of SCs differed extensively along the length of control human EOMs, being twice as abundant in the anterior portion. Pax7-positive cells were also detected in non-traditional SC positions. EOMs from terminal ALS patients showed similar numbers of resting and activated SCs as the controls. In limb muscles of ALS patients, the number of resting and activated SCs ranged from low (similar to normal aged, sedentary individuals) to high numbers, especially in muscles with long duration of disease and varied between the upper and lower limbs. The EOMs maintained a high degree of innervation compared to hindlimb muscles of symptomatic SOD1G93A mice. MyHC slow tonic fibers were less abundant in ALS patients than in controls. The change seemed more pronounced in bulbar onset patients, and in this group of subjects only, there was a strong association between decline in MyHC slow tonic fibers and age of death. Notably, the decline in MyHC slow tonic fibers was unrelated to disease duration.

    Our data suggested that SCs play a minor role in the progression of ALS in general and in the sparing of the EOMs in particular. The generally preserved innervation in the EOMs of G93A mice may reflect distinct intrinsic properties relevant for sparing of the oculomotor system.  Even though the EOMs are relatively spared in ALS, MyHC slow tonic myofibers were selectively affected and this may reflect differences in innervation, as these fibers are multiply innervated.

  • 274.
    Tjust, Anton
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Satellite cells in extraocular muscles of ALS patients2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • 275.
    Tjust, Anton
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Danielsson, Adam
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Andersen, Peter M
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Pedrosa Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Impact of ALS on slow tonic myofiber composition in human extraocular musclesManuscript (preprint) (Other academic)
  • 276.
    Tjust, Anton E
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Brännstrom, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Pedrosa Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Unaffected motor endplate occupancy in eye muscles of ALS G93A mouse model2012In: Frontiers in bioscience (Scholar edition), ISSN 1945-0524, Vol. 4, p. 1547-1555Article in journal (Refereed)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) is a progressive, lethal neurodegenerative disorder characterised by selective loss of motor neurons with accompanying muscle paralysis and respiratory failure. Despite progressive paralysis in trunk and extremity muscles, disturbed eye motility is not a hallmark of ALS. Extraocular muscles (EOMs) of terminal ALS patients show far less morphological signs of disease than their limb muscles. One of the earliest signs of the disease in the transgenic G93A SOD1 mouse model of ALS is loss of motor neuron contact at the neuromuscular junctions (NMJ) in limb muscles. We used immunohistochemistry to identify NMJs and evaluate innervation in EOMs and limb muscles of G93A mice. In G93A limb muscles, loss of axonal contact was seen in 6-82 percent of the NMJs. On the contrary, the degree of endplate occupancy in the EOMs did not differ between transgenic mice and wild-type controls. We propose that EOM-specific properties make these muscles more resistant to the underlying pathophysiological process of ALS and that the EOMs are a useful model to advance our understanding of ALS.

  • 277.
    Tjust, Anton E.
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Danielsson, Adam
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Brännstrom, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Medical Biosciences. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Impact of Amyotrophic Lateral Sclerosis on Slow Tonic Myofiber Composition in Human Extraocular Muscles2017In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 58, no 9, p. 3708-3715Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To analyze the proportion and cross-sectional area of myofibers containing myosin heavy chain slow-twitch (MyHCI) and myosin heavy chain slow tonic (MyHCsto) in extraocular muscles of autopsied amyotrophic lateral sclerosis (ALS) patients with either spinal or bulbar site of disease onset. METHODS. Whole-muscle cross sections from the middle portion of the medial rectus were labeled with antibodies against MyHCI or MyHCsto and laminin. Myofibers labeled with the MyHC antibodies (MyHCI+sto) and the total number of myofibers were quantified in the orbital and global layer of 6 control individuals and 18 ALS patients. The cross-sectional area of myofibers labeled for either MyHC was quantified in 130 to 472 fibers/individual in the orbital and in 180 to 573 fibers/individual in the global layer of each specimen. RESULTS. The proportion of MyHCI+sto myofibers was significantly smaller in the orbital and global layer of ALS compared to control individuals. MyHCI+sto myofibers were significantly smaller in the global layer than in the orbital layer of ALS, whereas they were of similar size in control subjects. The decreased proportion of MyHCI+sto fibers correlated significantly with the age of death, but not disease duration, in patients who had the bulbar-onset variant of ALS but not in patients with spinal variant. CONCLUSIONS. ALS, regardless of site of onset, involves a loss of myofibers containing MyHCI+sto. Only in bulbar-onset cases did aging seem to play a role in the pathophysiological processes underlying the loss of MyHCI+sto fibers.

  • 278.
    Tjust, Anton E.
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Danielsson, Adam
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Loss of myofibers containing MyHC Slow tonic in extraocular muscles of terminal ALS patients with bulbar onset2016In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, no 12Article in journal (Refereed)
  • 279.
    Tjust, Anton
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindström, Mona
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Sjöström, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Andersen, Peter M
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Pedrosa Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Satellite cells and other muscle progenitor cells in extraocular muscles and limb muscles of ALS donorsManuscript (preprint) (Other academic)
  • 280. Tolley, C.
    et al.
    Mullins, A.
    Kilgariff, S.
    Arbuckle, R.
    Green, J.
    Burstedt, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Holopigian, K.
    Stasi, K.
    Sloesen, B.
    Qualitative interviews to inform development of a patient reported outcome (PRO) strategy in RLBP1 retinitis pigmentosa (RLBP1 RP)2017In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 20, no 9, p. A761-A761Article in journal (Other academic)
    Abstract [en]

    Objectives: RLBP1 RP is a rare autosomal recessive form of retinitis pigmentosa (RP), characterized by night blindness, prolonged dark adaptation, constricted visual fields and reduced macular function. This study aimed to better understand the patient experience of RLBP1 RP and to evaluate the content validity of existing patient reported outcome (PRO) instruments in this condition. Methods: This qualitative study involved 90 minute, semi-structured, concept elicitation and cognitive debriefing interviews with patients with RLBP1 RP in Canada (n=10) and Sweden (n=11). Qualitative analysis of anonymized, verbatim transcripts was performed using Atlas.Ti software and thematic analysis methods. Participants were cognitively debriefed on The National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25), Low Luminance Questionnaire (LLQ) and four items of the Visual Activities Questionnaire (VAQ). Results: Fourteen visual symptoms were reported. The symptoms most frequently reported were night blindness (n=21), difficulty adapting to changes in lighting (n=21) and difficulties seeing in bright lighting (n=18). Impacts on daily activities (n=21) and physical functioning (n=17) were important to participants. Other domains of quality of life affected included social functioning (n=21), emotional functioning (n=19), work and education (n=18), and psychological functioning (n=17). Participant understanding and interpretation of the NEI VFQ-25 and LLQ was mixed. Patients reported that examples in single items represented different levels of functional impairment. In addition, some items did not specify what lighting conditions should be considered when responding. LLQ items were more relevant to RLBP1 RP than NEI VFQ-25 items. The four VAQ items assessing light/dark adaptation were well understood and relevant to participants. There were both gaps and overlaps in conceptual coverage of the instruments. Conclusions: The symptoms of RLBP1 RP have a substantial impact on patients’ daily lives and physical functioning. Issues have been identified with conceptual coverage, rel- evance and patient understanding of the NEI VFQ-25, LLQ and VAQ in RLBP1 RP.

  • 281.
    Viberg, Andreas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Liv, Per
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lundström, Mats
    Byström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    The impact of corneal guttata on the results of cataract surgery2019In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 45, no 6, p. 803-809Article in journal (Refereed)
    Abstract [en]

    Purpose: To study the impact of corneal guttata on postoperative visual acuity and patients' self-assessed visual function after cataract surgery.

    Setting: Patient data from 49 Swedish cataract surgery units.

    Design: Retrospective cross-sectional register-based study.

    Methods: Data from patients who had cataract surgery from 2010 to 2017 and completed the Catquest-9SF questionnaire were obtained from the Swedish National Cataract Register. Logistic proportional odds regression was used to model the impact of corneal guttata on the visual acuity and self-assessed visual function. Adjustments were made for age, sex, ocular comorbidities, days to follow-up, preoperative corrected distance visual acuity (CDVA) and preoperative Rasch person score. The main outcome measures were postoperative CDVA and Rasch person score calculated from the Catquest-9SF questionnaire.

    Results: The study comprised data from 33 741 patients. Cataract surgery greatly improved CDVA and self-assessed visual function in patients both with and without corneal guttata. Still, corneal guttata was significantly associated with a poorer visual acuity and a worse self-assessed visual function after cataract surgery. The negative effect of corneal guttata on visual acuity was most prominent during the first 3 weeks postoperatively, but it persisted at least 3 months postoperatively.

    Conclusions: Patients with corneal guttata benefit substantially from cataract surgery but have an additional risk for inferior results compared with patients without corneal guttata. These findings could serve as valuable tools in clinical practice, in particular, when deciding to perform cataract surgery and how to inform the patient about surgical benefits and risks.

  • 282.
    Vicente, André
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Byström, B.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Domellöf, Fatima Pedrosa
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Vivinex (c) toric lenses refractive results after cataract surgery, preliminary study including 50 eyes2018In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 96, p. 135-135Article in journal (Other academic)
  • 283.
    Vicente, André
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Byström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Domellöf, Fatima Pedrosa
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Altered Signaling Pathways in Aniridia-Related Keratopathy2018In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 13, p. 5531-5541Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To study the Notch1, Wnt/beta-catenin, sonic hedgehog (SHH), and mammalian target of rapamycin (mTOR) cell signaling pathways in naive and surgically treated corneas of aniridia cases with advanced aniridia-related keratopathy (ARK).

    METHODS. Two naive corneal buttons from patients with advanced ARK submitted to penetrating keratoplasty for the first time, one corneal button from an ARK patient that had undergone a keratolimbal allograft (KLAL), two corneal buttons from ARK patients who had previously undergone centered or decentered transplantation, and two adult healthy control corneas were processed for immunohistochemistry in this descriptive study. Antibodies specific against elements of the Notch1 (Notch1; Dlk1; Numb), Wnt/beta-catenin (Wnt5a; Wnt7a; beta-catenin), SHH (glioma-associated oncogene homolog [Gli1]; Hes1), and mTOR (mTOR1; ribosomal protein S6 [rpS6]) signaling pathways were used as well as antibodies against PAX6 and keratin 13 (Krt13).

    RESULTS. All ARK corneas presented signs of conjunctivalization and analogous signaling pathway changes in the subepithelial pannus and epithelium, with decreased detection of the Notch1 signaling pathway and an increased presence of the Notch1 inhibitors Numb and Dlk1. Increased detections of Wnt/beta-catenin (enhanced presence of Wnt5a, Wnt7a, and beta-catenin), SHH (detection of Gli1 and Hes1), and mTOR (identification of mTOR and rpS6) signaling pathways were found in the subepithelial pannus and epithelium of all ARK corneas, when compared with normal controls.

    CONCLUSIONS. The similarity in pathway alterations found in all ARK corneas, irrespective of limbal stem cell transplantation, further supports the discussion on the role of host-specific factors and limbal stem cell deficiency in ARK.

  • 284.
    Vicente, André
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Byström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindström, Mona
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Stenevi, Ulf
    Pedrosa Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Aniridia-related keratopathy: structural changes in naïve and transplanted corneal buttons2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 6, article id e0198822Article in journal (Refereed)
    Abstract [en]

    Background: To study structural changes in naive and surgically treated corneas of aniridia patients with advanced aniridia-related keratopathy (ARK).

    Methods and findings: Two naive corneal buttons from patients with advanced ARK submitted to penetrating keratoplasty for the first time, one corneal button from an ARK patient that had undergone a keratolimbal allograft (KLAL), two corneal buttons from ARK patients who had previously undergone centered or decentered transplantation and were now retransplanted and two adult healthy donor control corneas were processed for immunohistochemistry. Antibodies against extracellular matrix components in the stroma and in the epithelial basement membrane (collagen I and IV, collagen receptor alpha 11 integrin and laminin alpha 3 chain), markers of fibrosis, wound healing and vascularization (fibronectin, tenascin-C, vimentin, alpha-SMA and caveolin-1), cell division (Ki-67) and macrophages (CD68) were used. Naive ARK, KLAL ARK corneas and transplanted corneal buttons presented similar histopathological changes with irregular epithelium and disruption or absence of epithelial basal membrane. There was a loss of the orderly pattern of collagen lamellae and absence of collagen I in all ARK corneas. Vascularization was revealed by the presence of caveolin-1 and collagen IV in the pannus of all ARK aniridia corneas. The changes observed in decentered and centered transplants were analogous.

    Conclusions: Given the similar pathological features of all cases, conditions inherent to the host seem to play an important role on the pathophysiology of the ARK in the long run.

  • 285.
    Vicente, André
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Faculty of Medicine, Visual Sciences Study Center, Lisbon University, Lisbon, Portugal.
    Pedrosa Domellöf, Fátima
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Byström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Exophiala phaeomuriformis keratitis in a subarctic climate region: a case report2018In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 96, p. 425-428Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To report a case of Exophiala phaeomuriformis mycotic keratitis in a patient from a subarctic climate region. Dematiaceous fungi (black yeasts) have been gaining importance as corneal keratitis and ulcer causative agents in certain regions, but no cases have been described in Scandinavia.

    METHODS: Case report of a patient with a persistent corneal erosion that eventually presented a brown-pigmented infiltrate. The patient had a history of several months of topical therapy comprising medication for glaucoma, corticosteroids and antibiotics. A therapeutic contact lens was used, and amniotic membrane transplantation was performed before the development of the pigmented infiltrate.

    RESULTS: Exophiala phaeomuriformis was identified on the microbiological cultures from the surgically obtained infiltrate scrapes. The patient responded to topical amphotericin and fluconazole, the erosion was cured and a stromal scar subsided. During follow-up, sequential slit-lamp images and anterior segment optical coherence tomography (OCT) scans were obtained.

    CONCLUSION: This is the first described case of keratitis caused by E. phaeomuriformis in a subarctic region, the first in Europe and, to our knowledge, the second reported case in the literature. It is important to remember that superficial corneal brown-pigmented infiltrates should raise the suspicion of an unusual fungal infection even in this climate. This is particularly important in patients with ocular surface disease treated with steroids and antibiotics for a long time.

  • 286.
    Vicente, André
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Visual Sciences Study Center, Faculty of Medicine, Lisbon University.
    Prud'homme, Sylvie
    Ferreira, Joana
    Abegão Pinto, Luís
    Stalmans, Ingeborg
    Open-Angle Glaucoma: Drug Development Pipeline during the Last 20 Years (1995-2015)2017In: Ophthalmic Research, ISSN 0030-3747, E-ISSN 1423-0259, Vol. 57, no 4, p. 201-207Article, review/survey (Refereed)
    Abstract [en]

    OBJECTIVES: To analyse drug development for open-angle glaucoma during the last 20 years.

    METHODS: Research was performed by referring to clinical trials registered at the International Clinical Trials Registry Platform (ICTRP). A search for the condition "open-angle glaucoma" with the intervention "drug" was performed. We included trials registered from 01/01/1995 to 01/01/2015, only involving studies in phases 1, 2, and 3. Only studies resorting to novel treatment strategies (either novel drugs or yet-untested fixed associations of approved medication) were considered.

    RESULTS: We recorded 158 studies for the condition of open-angle glaucoma with a drug-based intervention; 65 of the studies reported phase 2 trials and 74 reported phase 3 trials. Pharmaceutical companies were the primary sponsors of 95.3% of the trials. Most of the studies (66.5%, n = 105) involved a new drug, and the remainder (33.5%, n = 53) tested fixed drug associations. The bulk of the trials (n = 99, 62.7%) involved the use of prostaglandin analogues, either as a comparator or a study drug. In descending order of frequency, the studies conducted involved Rho-kinase inhibitors (n = 15), carbonic anhydrase inhibitors (n = 14), β-blockers (n = 7), angiostatic steroids (n = 6), α2-adrenergic agonists (n = 4), 5-HT2A receptor agonists (n = 4), and NMDA receptor antagonists (n = 2). A cyclin-dependent kinase inhibitor, an LIM-domain kinase 2 inhibitor, an A1 adenosine receptor agonist, catechin, macrolide, saffron, and seawater were each tested in 1 clinical trial.

    CONCLUSION: Research into the medical treatment of glaucoma indicates the use of prostaglandin analogues. However, there are a significant number of trials testing other drug classes, particularly Rho-kinase inhibitors. This new focus could lead to a potential increase in the number of therapeutical options for the management of glaucoma in the future.

  • 287.
    Wang, Ling
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Department of Ophthalmology, Ruijin Hospital, Medicine School of Shanghai, Jiaotong University, Shanghai, China.
    el Azazi, Mildred
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Burstedt, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Wachtmeister, Lillemor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    The response of the neuronal adaptive system to background illumination and readaptation to dark in the immature retina2015In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 93, no 2, p. 146-153Article in journal (Refereed)
    Abstract [en]

    Purpose: Developmental characteristics of the neuronal adaptive system of the retina, focusing on background light (BGL) adaptation and readaptation functions, were studied by measuring the oscillatory response (SOP) of the electroretinogram (ERG).

    Methods: Digitally filtered and conventional ERGs were simultaneously recorded. Rats aged 15 and 17 days were studied during exposure to BGLs of two mesopic intensities and during readaptation to dark.

    Results: Results were compared to adult rats. In ‘low mesopic’ BGL SOP instantly dropped significantly to about half of its dark-adapted (DA) value contrary to mature rats, in which the SOP significantly increased. In ‘high mesopic’ BGL SOP decreased to about 20% and 30% of DA values in immature and adult rats, respectively. The process of recovery of SOP in darkness lacked the transient enhancement immediately as BGL was turned off, characteristic of adult rats. There were no major age differences in adaptive behaviour of a-wave. In young rats, recovery of b-wave was relatively slower.

    Conclusions: Properties of BGL adaptation and readaptation functions of the neuronal adaptive system in baby retina differed compared to the adult one by being less forceful and more restrained. Handling of mesopic illumination and recovery in the dark was immature. Development of these functions of the neuronal adaptive system progresses postnatally and lags behind that of the photoreceptor response and seems to be delayed also compared to that of the bipolar response.

  • 288. Weisschuh, Nicole
    et al.
    Stingl, Katarina
    Audo, Isabelle
    Biskup, Saskia
    Bocquet, Beatrice
    Branham, Kari
    Burstedt, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    De Baere, Elfride
    De Vries, Meindert J.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Green, Andrew
    Heckenlively, John
    Leroy, Bart P.
    Meunier, Isabelle
    Traboulsi, Elias
    Wissinger, Bernd
    Kohl, Susanne
    Mutations in the gene PDE6C encoding the catalytic subunit of the cone photoreceptor phosphodiesterase in patients with achromatopsia2018In: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 39, no 10, p. 1366-1371Article in journal (Refereed)
    Abstract [en]

    Biallelic PDE6C mutations are a known cause for rod monochromacy, better known as autosomal recessive achromatopsia (ACHM), and early-onset cone photoreceptor dysfunction. PDE6C encodes the catalytic alpha'-subunit of the cone photoreceptor phosphodiesterase, thereby constituting an essential part of the phototransduction cascade. Here, we present the results of a study comprising 176 genetically preselected patients who remained unsolved after Sanger sequencing of the most frequent genes accounting for ACHM, and were subsequently screened for exonic and splice site variants in PDE6C applying a targeted next generation sequencing approach. We were able to identify potentially pathogenic biallelic variants in 15 index cases. The mutation spectrum comprises 18 different alleles, 15 of which are novel. Our study significantly contributes to the mutation spectrum of PDE6C and allows for a realistic estimate of the prevalence of PDE6C mutations in ACHM since our entire ACHM cohort comprises 1,074 independent families.

  • 289.
    Westborg, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Safety and  efficacy in the cataract surgery process2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background

    Cataract and age-related macular degeneration (AMD) are two major causes for visual impairment in the elderly. Cataract surgery is one of the most common surgical interventions performed in the western world. As a consequence of the increasing number of operations performed, postoperative visits are a large workload for surgical units. It is important that all parts of the cataract surgery procedure are appropriate and cost-effective. During the last 20 years the trend is towards fewer visits both pre- as well as postoperatively. The number and timing of postoperative visits are also a subject of an ongoing debate. Few studies have previously evaluated safety perspectives concerning the number and timing of post-operative visits.

    The last decade, new treatments for wet AMD have evolved and the number of patients receiving treatment has increased. It has been debated if blue-blocking intraocular lenses (IOL) have a protective effect on the development of wet AMD and decreasing the need for AMD-treatment after cataract surgery.

    Aims

    To analyse parts of the modern cataract surgery process including peri- and post-operative routines from a safety and efficacy perspective. To analyse pre- and perioperative risk factors as well as protective factors associated with the need for wet AMD-treatment after cataract surgery.

    Methods

    I, II. These prospective, observational cohort studies included all cataract surgery cases (n=1249) during a 1-year period, at one institution. The cohort was analysed regarding the use of a standardized anaesthetic regimen and the safety perspectives, when the standard routine is no planned postoperative visit in uncomplicated cases without ocular comorbidity.

    III. The above-mentioned cohort (study group), was compared with a cohort from another clinic (control group) with a different follow-up routine, i.e. each case with first eye cataract surgery had a planned postoperative visit. In the control group all patients (n= 1162 cases) had surgery during the same 1-year period. The number of planned and unplanned visits was recorded, and the surgical outcome from the two institutions was compared.

    IV. A register-based cohort study included all patients registered in the Swedish National Cataract Register and the Swedish Macula Register in 2010 - 2017, to find all eyes with past cataract surgery that were subsequently treated for wet AMD. Complete registry data was used for comparisons and analyses of pre- and peri-operative risk- and protective factors for wet AMD treatment after cataract surgery.

    Results

    I. A standardized anaesthetic method with topical and intracameral anaesthetics without sedation was used in most cases (90%). Median pain score after surgery was 0.7 (VAS 0-10) and most patients (97%) would choose the same anaesthetic method again.

    II, III. Evaluation of all medical records 2 years after the cataract surgery procedure, found no report of missed adverse events. Significantly less patients in the study group (9% vs 16%; p=0.000036) initiated a postoperative unplanned contact compared with the control group. Patients with 70 km or longer to the hospital were less inclined to seek unplanned care (p=0.016).

    IV. Female gender and high age are associated with an increased risk of needing treatment for wet AMD ≥1 year after cataract surgery. Eyes with a diagnosis of AMD preoperatively, and subsequently treated for wet AMD, had a significantly (p=0.023) lower degree of blue-blocking IOLs implanted at their previous cataract surgery.

    Conclusion

    I. A standardized anaesthetic method with topical and intracameral anaesthetics without sedation seems well tolerated by the patients, and is effective at cataract surgery, also in cases when complications/adverse events occur.

    II, III. Without compromising patient safety, it is possible to refrain from standard postoperative visits after cataract surgery in patients with uncomplicated surgery and no ocular comorbidity. A significant reduction in postoperative visits is only obtained if the standard routine applies to both first and second eye surgery.

    IV. Patients without preoperative AMD have no benefit from the use of blue-blocking IOLs. In patients with preoperatively diagnosed AMD, blue-blocking IOLs may offer some protection from the subsequent development of AMD.

  • 290.
    Westborg, Inger
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Albrecht, Susanne
    RC Syd Karlskrona, EyeNet Sweden.
    Granstam, Elisabet
    Center for Clinical Research, Uppsala University/County Council of Västmanland.
    Karlsson, Niklas
    Örebro University Hospital, Örebro, Sweden.
    Kugelberg, Maria
    St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
    Lundström, Mats
    Department of Clinical Sciences, Ophthalmology, Faculty of Medicine, Lund University, Sweden.
    Montan, Per
    St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Treatment of Age-Related Macular Degeneration after Cataract Surgery: A Study from the Swedish National Cataract and Macula RegistersManuscript (preprint) (Other academic)
  • 291.
    Westborg, Inger
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Albrecht, Susanne
    Rosso, Aldana
    Risk For Low Visual Acuity After 1 And 2 Years Of Treatment With Ranibizumab Or Bevacizumab For Patients With Neovascular Age-Related Macular Degeneration2017In: Retina, ISSN 0275-004X, E-ISSN 1539-2864, Vol. 37, no 11, p. 2035-2046Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate how patients with neovascular age-related macular degeneration treated with ranibizumab or bevacizumab respond to treatment in daily clinical practice.

    Methods: Data from the Swedish Macula Register on the treatment received by 3,912 patients during 2011 to 2014 is reported. Patients' characteristics at the first visit, visual acuity, number of injections, and reason for terminating the treatment if applicable are discussed. Furthermore, the risk of having poor vision (visual acuity under 60 Early Treatment Diabetes Retinopathy Study letters or approximately 20/60 Snellen) is calculated for the treated eye after 1 year and 2 years.

    Results: The treatment outcome depends on the visual acuity at the first visit. For patients with visual acuity more than 60 letters, the risk of having a visual acuity lower than 60 letters after 1 year or 2 years of treatment is approximately 20%. However, for patients with low visual acuity at diagnosis (fewer than 60 letters), the risk is approximately 60%. The risk of having a visual acuity lower than 60 letters does not depend on the choice of treatment drug.

    Conclusion: Treatment with anti-vascular endothelial growth factor intravitreal injections mainly maintains the visual acuity level, and only approximately 20% and 40% of the patients required vision rehabilitation after 1 year and 2 years, respectively.

  • 292.
    Westborg, Inger
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Granstam, Elisabet
    Rosso, Aldana
    Albrecht, Susanne
    Karlsson, Niklas
    Lövestam-Adrian, Monica
    Treatment for neovascular age-related macular degeneration in Sweden: outcomes at seven years in the Swedish Macula Register2017In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 95, no 8, p. 787-795Article in journal (Refereed)
    Abstract [en]

    Purpose: To present Swedish Macula Register (SMR) data regarding treatment of neovascular age-related macular degeneration (AMD) in clinical practice since 2008.

    Methods: A retrospective register-based study was conducted. Evaluation of baseline demographics, visual outcome and number of injections during this period is presented.

    Results: Mean age at diagnosis was 79 ± (SD) 8 years; 65% were female. The proportion of patients with <2 months' duration of symptoms increased from 26% in 2008 to 41% in 2014 (p = 0.001). Mean visual acuity (VA) at baseline increased from 54.3 ± 15.0 early treatment diabetic retinopathy study (ETDRS) letters in 2008 to 57.8 ± 15.6 letters in 2014 (CI95 2.6; 4.3; p < 0.001). Mean VA after 1 year of treatment increased from 57.8 ± 17.7 ETDRS letters for patients who started the treatment in 2008 to 62.8 ± 16.4 ETDRS letters in patients starting treatment in 2014 (CI95 2.67; 4.64; p < 0.001). During all study years, the proportion of patients with an improvement in VA of between 5 and 15 letters was around 30%, while 14% had VA improvement of more than 15 letters. The mean number of injections during the first treatment year increased from 4.3 ± 1.9 in 2008 to 5.9 ± 2.9 in 2014 (CI95 1.40; 1.67; p < 0.001). Seven-year follow-up of 322 eyes showed a mean change of -1 letters from baseline, with a mean of 21 injections for the entire period.

    Conclusion: The duration of symptoms before treatment decreased, while VA at baseline and after 1 year of treatment increased over the years and so did the number of injections. Long-term follow-up demonstrated stable VA.

  • 293.
    Westborg, Inger
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Eye Clinic, Sunderby Hospital, Luleå, Sweden.
    Mönestam, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Intracameral anesthesia for cataract surgery: a population-based study on patient satisfaction and outcome2013In: Clinical Ophthalmology, ISSN 1177-5467, E-ISSN 1177-5483, no 7, p. 2063-2068Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate if the standard anesthetic regimen - topical combined with intracameral anesthesia without sedation - in a population-based cohort of unselected cataract surgery cases is adequate, optimal, and good practice, or if improvements are necessary.

    METHODS: We conducted a prospective, observational study on all cases of cataract surgery during a 1-year period at one institution (n=1249). Data were collected from the patients' records. Outcome measures were use of preoperative sedation, type of anesthesia, complications, and adverse events. In a subgroup of patients (n=124) satisfaction with the anesthetic regimen was evaluated using a short questionnaire.

    RESULTS: Most cases (90%, 1125/1249) had combined topical and intracameral anesthesia without sedation. Patients who chose preoperative sedation (midazolam hydrochloride sublingually) were significantly younger and more often female (P=0.0001 and P=0.011, respectively). In the questionnaire subgroup, the median pain score after surgery was 0.7 (visual analog scale, 0-10). A pain score of 1.9 or less was reported by 76% of the patients. Patients reporting a pain score of 2 or more had sedation and additional anesthetics more often. No significant difference was found regarding age, sex, pulse rate, oxygen saturation, first or second eye surgery, or adverse intraoperative events for patients with pain scores of 1.9 or less and 2 or more.

    CONCLUSION: This large population-based series of small-incision phacoemulsification surgery shows that combined topical and intracameral anesthesia without sedatives is well tolerated for most phacoemulsification patients. It is also effective in cases when complications or adverse events occur. It is important to be responsive to the individual patient's needs and adjust operating procedures if necessary, as there were a few patients who experienced insufficient anesthesia.

  • 294.
    Westborg, Inger
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Mönestam, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Optimizing follow-up after cataract surgery: comparison of two institutionsManuscript (preprint) (Other academic)
  • 295.
    Westborg, Inger
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Mönestam, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Optimizing number of postoperative visits after cataract surgery - a safety perspective2013In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 91Article in journal (Other academic)
  • 296.
    Westborg, Inger
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Mönestam, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Optimizing number of postoperative visits after cataract surgery: Safety perspective2017In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 43, no 9, p. 1184-1189Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate safety perspectives when the standard routine after cataract surgery is no planned postoperative visit.

    Setting: Eye Clinic, Sunderby Hospital, Lulea, Norrbotten County, Sweden.

    Design: Prospective case series.

    Methods: All cataract surgery cases during a 1-year period were included. The study group had the standard routine at the clinic, that is, no planned postoperative visit for patients without comorbidity and uneventful surgery. For the control group, patients who had surgery during 1 month of the 1-year period were chosen. All these patients had a planned postoperative visit. All surgeons involved were experienced. The outcome measures were any planned postoperative visit, any complication and/or adverse event, postoperative corrected distance visual acuity (CDVA), and any postoperative control/contact initiated by the patient.

    Results: The study comprised 1249 patients (1115 in the study group and 134 in the control group). No significant differences in demographics, postoperative CDVA, frequency of planned visits because of ocular comorbidity, or postoperative patient-initiated contacts were found between the 2 groups. Of the 1249 patients, 9% (117 patients) initiated a postoperative contact, of whom 26% (30 patients) also had a scheduled visit. The reasons for the patient-initiated contacts were visual disturbance, redness and/or chafing, pain, and anxiety. An evaluation of all medidal records 2 years postoperatively found no reports of missed adverse events.

    Conclusions: It was possible to refrain from planned,postoperafive visits for patients having uncomplicated cataract surgery. However, preoperatively, patients with comorbidities should be provided with individual planning of their postoperative follow-up. Preoperative counseling is important, and the clinic must have resources to answer questions from patients and be prepared for additional unplanned postoperative visits.

  • 297.
    Westborg, Inger
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Rosso, Aldana
    Risk factors for discontinuation of treatment for neovascular age-related macular degeneration2018In: Ophthalmic Epidemiology, ISSN 0928-6586, E-ISSN 1744-5086, Vol. 25, no 2, p. 176-182Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate risk factors for treatment discontinuation for neovascular age-related macular degeneration (nAMD).

    Methods: Data from the Swedish Macula Register and the Skane Healthcare Register are reported on the treatment received by 932 nAMD patients diagnosed 2013-2015. Treatment discontinuation is defined as having a termination visit or lacking a control or treatment visit during the period of 10-14months after the diagnostic visit. The risk of treatment discontinuation during the first year is estimated using a Poisson model and a classification tree.

    Results: 503 eyes (50.9%) discontinued the treatment within the first year. Patients with visual acuity below 60 ETDRS letters (20/60 Snellen) at baseline, serious comorbidities, or treated at the university hospital have a 42% (95% CI 25-61%, P<0.001), 27% (95% CI 13-43%, P=0.001) and 30% (95% CI 15-46%, P<0.001) increased risk to discontinue treatment compared with similar patients. Patients on ranibizumab therapy have a 45% (95% CI 28-63%, P<0.001) increased risk for treatment discontinuation during year 1 compared with patients on aflibercept therapy. The classification tree also shows that patients on ranibizumab therapy and those with low VA at baseline are at a higher risk of terminating treatment.

    Conclusions: Almost half of the patients starting anti-VEGF therapy discontinue treatment during the first year. Patients with risk factors may require additional support to continue with the treatment. Aflibercept therapy could be an alternative to patients at risk of treatment discontinuation.

  • 298.
    Westborg, Inger
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Rosso, Aldana
    Risk for low visual acuity after 1 and 2 years of treatment with anti-VEGF. Comparison of different agents: Ranibizumab, Aflibercept, and Bevacizumab2018In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 9Article in journal (Other academic)
    Abstract [en]

    Purpose : To analyze the risk factors for low visual acuity and compare the visual acuity, number of visits and injections received by patients on different anti-vascular endothelial growth factor (anti-VEGF) therapies after one and two years of treatment.

    Methods : Retrospective register-based cohort study from the national Swedish Macula Register (SMR). Treatment naïve eyes and treated exclusively with ranibizumab, bevacizumab or aflibercept, followed for two years. Evaluation of baseline characteristics as age, best corrected visual acuity (BCVA) and type of lesion and treatment drug. The risks of low visual acuity (BCVA ≤60 ETDRS letters) during the first and second year were estimated.

    Results : Mean BCVA were 56.2, 62 and 62.5 ETDRS letters for baseline, year 1 and year 2 respectively. Aflibercept eyes received 5.9 injections year one and 3.9 year two. Bevacizumab and ranibizumab treated eyes received 5.3 and 4.7 injections year one and 3.8 and 3.1 injections year two respectively. The average number of vists in the ranibizumab and bevazicumab groups was slightly higher compared to aflibercept group both year 1 and 2. VA improved on average in all treatment groups. At year one 33% of eyes in Aflibercept and Bevacizumab and 34% in Ranibizumab treated group had a VA of less than 60 ETDRS letters. Number of eyes discontiuning treatment or lost to follow-up after two years were 55% (2016/3678). Low visual acuity were the main reason for discontinuation. Older patients and low baseline VA were risk factors for low VA after one and two years of treatment.

    Conclusions : This study show a shift in treatment regimen in Sweden 2013 with increasing number of injections and an inclination to follow label with fewer visits and more injections instead of PRN (Pro re nata) regimen. Maintenance in mean VA after one and two years is seen in all treatment groups but eyes treated with aflibercept show a slightly better mean VA after one and two years. However, it is worth noticing that those patients have on average a better baseline VA. Treatment are also maintained in a higher degree for aflibercept treated eyes. Risk factors for low visual acuity after one and two years of treatment are, as expected, older patients and low baseline VA.

  • 299.
    Westin, Oscar
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Epidemiology and Outcomes in Refractive Lens Exchange Surgery2013Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 300.
    Westin, Oscar
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Koskela, Timo
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Epidemiology and outcomes in refractive lens exchange surgery2015In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 93, no 1, p. 41-45Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To assess demographics and refractive outcomes in patients undergoing refractive lens exchange surgery (RLE), with a population of cataract patients as a reference.

    METHODS: A RLE cohort from a private eye clinic (n = 675) and a cataract cohort from the outcome registration of the Swedish National Cataract Register were studied and compared from an epidemiological perspective regarding age, gender, preoperative refraction and postoperative refractive outcome.

    RESULTS: The RLE patients were younger (52.1 ± 7.7 versus 73.84 ± 9.32 years) with a smaller percentage of women (45.28% versus 60.46%; p < 0.001) and were more often myopic than the cataract patients. Astigmatism and hyperopia did not differ between the cohorts. Uncorrected visual acuity after RLE equalled the best corrected visual acuity in best cases after cataract surgery. The absolute biometry prediction was more accurate in RLE (0.17 ± 0.27 D versus 0.40 ± 0.58 D; p < 0.001), particularly in patients given a customized toric IOL (0.12 ± 0.27 D; p < 0.05). In cataracts, the Haigis' formula showed higher accuracy than the SRK/T formula (0.39 ± 0.53 D versus 0.43 ± 0.61 D; p < 0.01). Postoperatively after RLE, Laser Epithelial Keratomileusis was performed in 9.04% and Yttrium Aluminium Garnet capsulotomy in 7.41% of the eyes. Other reoperations were performed in three cases, and five postoperative retinal detachments occurred after RLE.

    CONCLUSION: Compared with patients undergoing cataract surgery, we see many similarities, but also many interesting differences in patients undergoing RLE. Basic information about the growing population choosing to undergo RLE can help us plan future ophthalmic care.

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