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  • 251.
    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.

  • 252.
    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
  • 253.
    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)
  • 254.
    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.

  • 255.
    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.
    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.

  • 256.
    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)
  • 257.
    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)
  • 258. 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.

  • 259.
    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.

  • 260.
    Vicente, André
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    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 report.2017In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768Article 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.

  • 261.
    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.

  • 262.
    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.

  • 263.
    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.

  • 264.
    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.

  • 265.
    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.
    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.

  • 266.
    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)
  • 267.
    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.

  • 268.
    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.

  • 269.
    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
  • 270.
    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.

  • 271.
    Zhang, Wei
    et al.
    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.
    Backman, Ludvig J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Malm, Adam D.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Surface Topography and Mechanical Strain Promote Keratocyte Phenotype and Extracellular Matrix Formation in a Biomimetic 3D Corneal Model2017In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 6, no 5, article id UNSP 1601238Article in journal (Refereed)
    Abstract [en]

    The optimal functionality of the native corneal stroma is mainly dependent on the well-ordered arrangement of extracellular matrix (ECM) and the pressurized structure. In order to develop an in vitro corneal model, it is crucial to mimic the in vivo microenvironment of the cornea. In this study, the influence of surface topography and mechanical strain on keratocyte phenotype and ECM formation within a biomimetic 3D corneal model is studied. By modifying the surface topography of materials, it is found that patterned silk fibroin film with 600 grooves mm(-1) optimally supports cell alignment and ECM arrangement. Furthermore, treatment with 3% dome-shaped mechanical strain, which resembles the shape and mechanics of native cornea, significantly enhances the expression of keratocyte markers as compared to flat-shaped strain. Accordingly, a biomimetic 3D corneal model, in the form of a collagen-modified, silk fibroin-patterned construct subjected to 3% dome-shaped strain, is created. Compared to traditional 2D cultures, it supports a significantly higher expression of keratocyte and ECM markers, and in conclusion better maintains keratocyte phenotype, alignment, and fusiform cell shape. Therefore, the novel biomimetic 3D corneal model developed in this study serves as a useful in vitro 3D culture model to improve current 2D cultures for corneal studies.

  • 272. Åsman, Peter
    et al.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Internet-based assessment of medical students' ophthalmoscopy skills2010In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 88, no 8, p. 854-857Article in journal (Refereed)
    Abstract [en]

    Purpose: Ophthalmoscopy is an important skill in undergraduate medical education. The use and outcome of a novel Internet-based method for assessing motor skills-related aspects of ophthalmoscopy skills in medical students are described. Methods: A total of 139 students in Malmö and 255 students in Umeå were assessed during four consecutive semesters. An optic disc photograph was obtained in each student. At assessment each student was asked to examine the eye of a fellow student. Fifteen disc photographs were displayed on a computer screen. One of the photographs was from the fellow student. The remaining images had been randomly selected. The student was asked to identify the optic disc of the fellow student from the 15 photographs on the screen. In one semester, the time spent on this by each student was recorded. Results: All students completed the task. The average pass ratio was 96.4% (ranging from 94.0% to 98.0%). Median student times were 5.53 mins in Malmö and 6.36 mins in Umeå. Conclusions: This is the first automated, Internet-based assessment of an ophthalmic motor skill performed in co-operation between universities. The method used bears more similarities to real-life ophthalmoscopy than methods that use model eyes. Time investments and infrastructure demands were comparatively low. The method was designed for stand-alone assessment of ophthalmoscopy or as an objective structured clinical examination station, but it may also be used during the learning process. The collaboration between universities was easily transformed into routine practice and similar projects should be encouraged to increase the standardization of assessment

  • 273.
    Åström, Siv
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Long-term follow-up of pseudoexfoliation, intraocular pressure and glaucoma: epidemiological studies in northern Sweden2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Purpose An age-cohort was studied with long-term follow-up. The population was born in 1915, living in the municipality of Skellefteå in 1981. The purpose was to investigate the prevalence and incidence of pseudoexfoliation (PEX), its influence on intraocular pressure (IOP) and development of open-angle glaucoma (OAG). Another purpose was to estimate the value of screening for glaucoma by comparing the screened group within the cohort with the remaining unscreened group.

    Methods In 1981, 339 (40%) of the 856 individuals in the cohort underwent an eye examination. This screened group was re-examined at seven-year intervals until 2002. At each visit the presence of PEX was registered, IOP was measured and the presence of glaucoma was assessed. After the 21-year follow-up period, glaucoma cases were also searched for in the medical records of the remaining unscreened individuals in the cohort. Proportions of glaucoma were compared between the two groups.

    Results The prevalence of PEX was 23% (95% confidence interval (CI): 20-26%) at the age of 66 and increased to 61% (CI: 50-71%) at the age of 87. The annual incidence of PEX was 1.8% (CI: 1.3-2.4%). The prevalence of OAG increased from 2.1% (CI: 0.8-4.3%) at the age of 66 years to 25 % (CI: 16-35%) at 87 years. The overall annual incidence of OAG was 0.9% (CI: 0.6-1.3%) and for OAG with PEX 2.1% (CI: 1.2-3.3%). PEX increased the risk of developing glaucoma at least four-fold. The incidence of diagnosed OAG in women was higher in the screened group than in the unscreened group (incidence rate ratio (IRR)=1.94, p=0.035). A corresponding difference could not be verified for men (p=0.58). The mean, agedependent, increase in IOP during the 21-year observation period was 0.05 mmHg/year.

    Conclusion The prevalence of PEX in this study population was the highest reported, and it increased with age. The presence of PEX increased the risk of developing OAG four times. In this study a higher proportion of OAG was revealed by screening among women but not among men. The age-related IOP increase was clinically insignificant.

  • 274.
    Åström, Siv
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Diagnosed open-angle glaucoma in screened versus unscreened subjects: a long-term age cohort study2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 6, p. 501-506Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate and compare the cumulative incidence of diagnosed open-angle glaucoma (OAG) in an age cohort of elderly people, of which one group was screened. METHODS: Cohort study comprising all 856 individuals born in 1915 and living in the municipality of Skellefteå in1981. A randomly selected subgroup of the cohort (40%) was repeatedly screened, and suspected OAG cases were followed until 2002 for the development of OAG. Medical records were collected and analysed for OAG. The numbers of OAG cases were compared between the screened group and the remaining part of the cohort (the unscreened group). RESULTS: The cohort consisted of 339 screened and 517 unscreened persons. Before 1981, there were six known cases of OAG in the screened group and nine cases in the unscreened group. During the follow-up from 1981 to 2002, there were 33 new cases in the screened group and 31 new cases of OAG in the unscreened group. The incidence of diagnosed OAG in women was higher in the screened group than in the unscreened group, incidence rate ratio = 1.94 (p = 0.035). In contrast, the cumulative incidence of diagnosed OAG in men was similar in the two groups (p = 0.58). For the whole population, there was no significant difference (p = 0.053) CONCLUSION: In this population with a high prevalence of PEX and increased risk for glaucoma, there was a non-significant difference between the screened and unscreened groups regarding the proportion of diagnosed OAG. The failure to reach significance may be due to the limited sample size. OAG was diagnosed twice as often among women in the screened group than in the unscreened group.

  • 275.
    Åström, Siv
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Incidence and prevalence of pseudoexfoliations and open-angle glaucoma in northern Sweden: II. Results after 21 years of follow-up.2007In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 85, no 8, p. 832-837Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To prospectively evaluate the prevalence and incidence of pseudoexfoliation (PEX) syndrome and open-angle glaucoma (OAG) with and without PEX and to evaluate PEX as a risk factor for glaucoma in a population born in 1915 and living in the municipality of Skellefteå in northern Sweden.

    METHODS: A randomized population study comprising 339 individuals. The cohort was followed for 21 years at 7 year intervals. The examination included tonometry, dilated slit-lamp biomicroscopy, optic disc evaluation and, if glaucoma was suspected, a visual field analysis.

    RESULTS: The prevalence of PEX increased from 23%[95% confidence interval (CI): 20-26] at 66 years of age to 61% (CI 50-71) at 87 years. The annual incidence of PEX was 1.8% (CI 1.3-2.4). In the group of subjects with unilateral PEX, 55% converted to bilateral PEX during follow-up. The prevalence of OAG was 2.1% (CI 0.8-4.3%) at 66 years of age and 25% (CI 16-35) at 87 years. Of the glaucoma cases, 59% had PEX. There was no difference in incidence between the sexes. The annual incidence of PEX and OAG did not increase with time. The overall annual incidence of OAG was 0.9% (CI 0.6-1.3%) [0.5% (CI 0.2-0.9) without PEX and 2.1% (CI 1.2-3.3) with PEX]. PEX increased the risk of glaucoma four fold in both sexes. There was no significant difference in mortality between individuals with or without PEX.

    CONCLUSION: PEX syndrome and OAG are common in the north of Sweden. Prevalences increase with age. PEX increases the risk of glaucoma four fold. The consequences of this situation demand guidelines for handling patients with PEX, with or without other risk factors. In order to issue guidelines, more information is needed on the impact of the disease on the general health in the ageing population.

  • 276.
    Åström, Siv
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Intraocular pressure changes over 21 years: a longitudinal age-cohort study in northern Sweden2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 5, p. 417-420Article in journal (Refereed)
    Abstract [en]

    Purpose:  To follow intraocular pressure (IOP) and the influence of pseudoexfoliation (PEX) and cataract extraction in an age-cohort in northern Sweden; patients were followed prospectively for 21 years from age 66 to 87 years.

    Methods:  Three Hundred and thirty-nine individuals, randomly selected from an age-cohort born in 1915 underwent ophthalmological examination including measurement of IOP with Goldmann applanation tonometry, screening for PEX and glaucoma. Follow-up examinations were performed three times with 7-year intervals. Medical records were reviewed for dates of cataract surgery and glaucoma treatment. A linear mixed model was used to analyse the impact of sex, eye (right/left), PEX, cataract extraction and time on IOP.

    Results:  Without cataract surgery, the IOP from age of 66 to 87 years, increased by 0.05 mmHg/year (p < 0.001). If cataract surgery was included in the model, no significant change in IOP over time was found. The estimated contribution of PEX to IOP was +2.05 mmHg (p < 0.001), and the contribution of cataract surgery was −2.13 mmHg (p < 0.001). The mean IOP in women was 1.22 mmHg higher than in men (p = 0.001).

    Conclusion:  A small but statistically significant increase in IOP with age was detected when excluding eyes that had undergone cataract surgery. PEX was associated with a higher IOP and cataract extraction with a lower.

  • 277.
    Åström, Siv
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Open-angle glaucoma in screened versus unscreened subjects: a long-term age-cohort studyArticle in journal (Other academic)
  • 278. Öhrstrom, Arne
    et al.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Silicone oil bubbles in ophthalmic viscosurgical devices.2002In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 28, no 3, p. 389-Article in journal (Refereed)
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