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  • 201.
    Lundqvist, Oskar
    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.
    A paired comparison of intracameral mydriatics in refractive lens exchange surgery2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 5, p. 482-485Article in journal (Refereed)
    Abstract [en]

    Purpose: To compare the efficacy and intra-operative safety of intracameral mydriatics to topical mydriatics in patients undergoing refractive lens exchange (RLE) surgery. Methods: In a randomized intra-individually comparing study performed at Koskelas Eye Clinic, Lulea, and Department of Clinical Sciences/Ophthalmology, Umea University Hospital, Umea, Sweden, 56 patients undergoing same-day bilateral RLE were included. Pupils were randomly dilated with topical mydriatics in one eye and intracameral mydriatics in the fellow eye. Pupil sizes were recorded intra-operatively throughout the procedures. Perceived pain/discomfort and glare were assessed immediately postoperatively using a visual analogue scale from 0 to 10. Results: Topical mydriatics and intracameral mydriatics both give satisfactory pupil dilation in routine RLE. However, there was noticeable iris billowing in 17 eyes dilated with topical mydriatics but only one eye with intracameral mydriatics (p < 0.001). Pupils were initially slightly larger in the topical mydriatics group but contracted during surgery. There was no perceived difference with regards to glare, pain or discomfort between the treatments. The surgeon graded intracameral mydriatics eyes as easier to operate on. Conclusion: Both topical mydriatics and intracameral mydriatics give satisfactory mydriasis for RLE, but pupil constriction and iris billowing are more pronounced with topical mydriatics.

  • 202.
    Lundqvist, Oskar
    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.
    Gender differences in refractive prediction in refractive lens exchange surgery2015In: European Journal of Ophthalmology, ISSN 1120-6721, E-ISSN 1724-6016, Vol. 25, no 2, p. 108-111Article in journal (Refereed)
    Abstract [en]

    Purpose: To compare the refractive outcomes after refractive lens exchange (RLE) surgery with regards to gender and intraocular lens (IOL) power calculation formula. Methods: A cohort of consecutive patients operated with bilateral same-day RLE surgery at a private eye clinic (n = 512) was studied. Target refraction was emmetropia in all cases and Haigis formula was used for all IOL power calculations. One month after surgery, subjective refraction was assessed and the absolute refractive prediction error (RPEAbs), as well as the refractive prediction error with correct signs (RPESign), was calculated, as were the refractive outcomes with the SRK/T formula. Results: For the whole cohort, the Haigis formula rendered a significantly smaller RPEAbs than the SRK/T formula (0.16 +/- 0.26 D vs 0.32 +/- 0.30 D; p<0.001). No gender difference in RPEAbs was seen. A slight myopic error was seen with the SRK/T formula in women, and a slight hyperopic error in men (-0.06 +/- 0.47 D vs + 0.16 +/- 0.39 D; p<0.001). No similar gender difference was seen with the Haigis formula (+ 0.05 +/- 0.29 D vs + 0.05 +/- 0.31 D; p = NS). Axial length, anterior chamber depth, and corneal steepness differed significantly between the sexes. Conclusions: The Haigis formula generally performed better in this RLE cohort. The SRK/T formula generates a small myopic error in women and a hyperopic error in men, associated with flatter corneas, longer axial lengths, and deeper anterior chambers in the latter.

  • 203. Lundstrom, Mats
    et al.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Kugelberg, Maria
    Montan, Per
    Stenevi, Ulf
    Thorburn, William
    Decreasing rate of capsule complications in cataract surgery Eight-year study of incidence, risk factors, and data validity by the Swedish National Cataract Register2011In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 37, no 10, p. 1762-1767Article in journal (Refereed)
    Abstract [en]

    Purpose: To define the incidence of capsule complication and its risk factors in Sweden over an 8-year period.

    Setting: Fifty-two ophthalmic surgery units in Sweden.

    Design: Database study.

    Methods: Data were collected prospectively in the Swedish National Cataract Register (NCR) from 2002 through 2009. The NCR contains 97.3% of the total number of cataract extractions in Sweden over the 8-year study period. One mandatory variable in the register is capsule complications during surgery. As a means to validate the accuracy of register data on capsule complications, a randomly selected sample of 2400 registrations was compared with corresponding medical records.

    Results: The analyses were based on 602 553 cataract extractions reported to the NCR. A capsule complication was reported in 12 574 cataract extractions, corresponding to a frequency of 2.09%. The incidence of this complication consistently decreased each year from 2002 to 2006, after which it stabilized. Poor corrected distance visual acuity in the surgical eye (≤ 0.1), the occurrence ofglaucoma, diabetic retinopathy, and age were among the parameters significantly related to a capsule complication. Some of these parameters also decreased over time. However, even after adjusting for this, there was an obvious decrease in capsule complications over time. The validity test showed a certain underreporting of capsule complications to the registry, but it was not significant and did not change over time.

    Conclusion: The incidence of capsule complications decreased over time. This may be partly the result of fewer risk factors and of better surgical quality.

    Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

  • 204.
    Lundström, Anna-Lena
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Wang, Ling
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Wachtmeister, Lillemor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Neuronal adaptation in the human retina: a study of the single oscillatory response in dark adaptation and mesopic background illumination.2007In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 85, no 7, p. 756-763Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The single oscillatory response in complete dark adaptation (DA) and the effect of mesopic illumination were studied in order to investigate the behaviour of the neuronal adaptation system as reflected in the oscillatory potentials (OPs) of the electroretinogram (ERG). METHODS: The rapid oscillatory and slow components (a- and b-waves) of single ERGs were simultaneously recorded in nine healthy, young subjects in response to first flash after both DA of 45 mins and light adaptation to a steady background light (BGL) of low mesopic intensity. RESULTS: Two low-amplitude oscillatory peaks were present in the single response to the first flash recorded in DA. There was no increase in the summed amplitudes of the OPs (SOP) when recorded in the single response to the first flash in mesopic BGL. However, the morphology of the oscillatory response altered. The first OP was reduced and a third oscillatory peak appeared. CONCLUSIONS: We conclude that early, scotopically related OPs may indeed be activated in the single response to the first flash in DA (i.e. without using conditioning flashes). Secondly, on its own, adaptation to mesopic BGL does not seem to trigger enhancement of the overall oscillatory response. The altered single oscillatory response to the first flash apparent in the mesopic BGL comprises a third cone-associated OP and seems to reflect a reorganization of the retinal microcircuitry from a predominantly rod-activated system to one of mixed rod/cone neuronal activity in the inner part of the retina at the level at which individual OPs have their respective origins.

  • 205.
    Lundström, M
    et al.
    EyeNet Sweden, Blekinge Hospital, SE-371 85 Karlskrona.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Montan, Per
    Artzén, D
    Jakobsson, G
    Johansson, B
    Thorburn, William
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Stenevi, Ulf
    Inst för klinisk neurovetenskap, Sektionen för oftalmologi, Sahlgrenska universitetssjukhuset/Mölndal.
    Capsule complication during cataract surgery: Background, study design, and required additional care: Swedish Capsule Rupture Study Group report 1.2009In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 35, no 10, p. 1679-1687Article in journal (Refereed)
    Abstract [en]

    Purpose: To report the selection procedure of complicated and uneventful cataract extractions included in the Swedish Capsule RuptureStudy and to describe the additional care required after a capsule complication during cataract surgery.

    Setting: Ten ophthalmic surgery departments in Sweden.

    Methods: Consecutive cataract extractions with a reported capsule complication were selected from the national database. Surgical data and data from the matching ophthalmic records at the participating clinics were analyzed. Controls were selected as the first uneventful procedure in the database after each procedure with a complication.

    Results: Data on 655 cataract extractions were studied for evaluation of risks and additional care; a capsule complication occurred in 324 procedures and no complication in 331 procedures. Using these records, 369 patients were recruited for a follow-up examination of the outcomes 3 years after the original cataract extraction. The records showed a substantial increase in additional care after a capsule complication, including more visits after surgery, increased need for in-patient care, and a significantly greater percentage of reoperations than after the uneventful surgery. With additional care, the average cost of a procedure with a capsule complication was approximately double the cost of an uneventful cataract extraction.

    Conclusions: The combined study of the database and matching medical records showed a substantial increase in additional care after a capsule complication. Using the database allowed identification of a large number of capsule complication cases and uneventful cases, indicating that national databases are excellent sources of data for studying unusual complications.

  • 206.
    Lundström, Mats
    et al.
    EyeNet Sweden, Blekinge Hospital, Karlskrona.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Kugelberg, M
    EyeNet Sweden, Blekinge Hospital, Karlskrona.
    Montan, P
    EyeNet Sweden, Blekinge Hospital, Karlskrona.
    Stenevi, Ulf
    Sektionen för oftalmologi, Sahlgrenska universitetssjukhuset/Mölndal.
    Pesudovs, K
    The outcome of cataract surgery measured with the Catquest-9SF2011In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 89, no 8, p. 718-723Article in journal (Refereed)
    Abstract [en]

    Purpose: The purpose of this study was to use the Catquest-9SF to measure cataract surgery outcomes, and to use Rasch analysis to test the psychometric properties of this questionnaire, including its validity and responsiveness. Methods: Patients were recruited as consecutive cataract surgery patients during 1 month at six surgical units in Sweden (via the National Cataract Register). The patients completed the questionnaire before surgery and 3 months after. The Catquest-9SF data were assessed for fit to the Rasch model using version 3.63.2 of the WINSTEPS software (Winsteps.com, Beaverton, OR, USA). Both preoperative and postoperative questionnaires were included in the analysis. The responsiveness to cataract surgery was calculated as the effect size. Results: Completed questionnaires before and after surgery were received from 846 patients. The Rasch analysis showed that the category thresholds were ordered. All items fit a single overall construct (infit range 0.79-1.40; outfit range 0.74-1.40). The ability to discriminate different strata of person ability was good, with a real patient separation of 2.58 and patient separation reliability of 0.87. The questionnaire showed unidimensionality and was largely free from differential item functioning. The item difficulty was reasonably well targeted to both preoperative and postoperative patient ability. The Catquest-9SF Rasch score correlated significantly with visual acuity, and cataract surgery resulted in a significant improvement with an effect size of 1.8. Conclusion: The Catquest-9SF shows excellent psychometric properties, as demonstrated by Rasch analysis. It is highly responsive to cataract surgery, and its brevity (nine items) makes it well suited for use in daily clinical practice

  • 207.
    Lundström, Mats
    et al.
    EyeNet Sweden, Blekinge Hospital, Karlskrona, Sweden.
    Wejde, Gisela
    Gisela Wejde, MD, PhD, St. Erik’s Eye Hospital,Stockholm, .
    Stenevi, Ulf
    3Department of Ophthalmology, Sahlgren’s Hospital, Mölndal, Sweden..
    Thorburn, William
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Montan, Per
    2Department of Ophthalmology, St. Erik’s Eye Hospital, Stockholm.
    Endophthalmitis after cataract surgery: a nationwide prospective study evaluating incidence in relation to incision type and location.2007In: Ophthalmology (Rochester, Minn.), ISSN 0161-6420, E-ISSN 1549-4713, Vol. 114, no 5, p. 866-870Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To establish the nationwide rate of postoperative endophthalmitis (PE) after cataract extraction (CE) and to study the relationship between PE and type of incision and other possible risk factors. DESIGN: Prospective, multicenter, comparative, nonrandomized, observational study. PARTICIPANTS: All cataract surgeries in Sweden performed from January 2002 through December 2004 and all endophthalmitis cases in the same period that were reported to the Swedish National Cataract Register (NCR). METHODS: Through a standard reporting form sent to the NCR, patient and operation technique data were recorded. In addition, PE cases with a traceable number to the main register were collected. Various parameters with a possible impact on endophthalmitis development were evaluated. Univariate analyses and logistic regression were statistical methods. MAIN OUTCOME MEASURES: The rate and etiology of PE; possible risk factors pertaining to patient history and operation technique, with a special emphasis on incision type and location; use of injector for the intraocular lens implantation; kind of prophylaxis; and presence of peroperative communication between the anterior chamber and vitreous. RESULTS: The overall rate of PE was 0.048% (109 cases in 225 471 CEs). Incidences of PE were 0.053% with clear corneal incisions and 0.036% with sclerocorneal incisions (P = 0.14, logistic regression analysis). The corresponding results were 0.040% for superior incisions and 0.055% for temporal incisions (P = 0.14). Communication between the anterior segment and vitreous was found to be a highly significant independent risk factor for PE (P<0.001), as were patient age > or = 85 years (P<0.001) and the nonuse of intracameral cefuroxime (P<0.001). CONCLUSIONS: The overall rate of PE after cataract surgery is low in Sweden, which may be a consequence of the widespread use of prophylactic intracameral cefuroxime. Only a trend for an increased risk of PE was detected for clear corneal and temporal wounds. The present data indicate that the use of clear corneal and/or temporal approaches will result in 1 additional PE case in approximately 5500 procedures on top of the PE rate after sclerocorneal or superior incisions, which was approximately 1 case in 2400 operations.

  • 208.
    Malm, Christer
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Hadrevi, Jenny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Bergström, Sven-Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Pedrosa-Domellof, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Svensson, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Frängsmyr, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Evaluation of 2-D DIGE for skeletal muscle: Protocol and repeatability2008In: The Scandinavian Journal of Clinical & Laboratory Investigation, Vol. 68, no 8, p. 793-800Article in journal (Refereed)
    Abstract [en]

    Proteomic analysis has the potential to yield vast amounts of data. The available proteomic methods have been hampered by methodological errors in quantification due to large gel-to-gel variations. The inclusion of an internal standard greatly reduces this variation, and therefore the purpose of this investigation was: 1) to develop a sample preparation protocol for human skeletal muscle for two-dimensional differentiated gel electrophoresis (DIGE) and 2) to investigate the repeatability of one particular system, the Ettan™ DIGE. To test repeatability, nine aliquots from the same homogenate were labelled with three different CyDye™ dyes (Cy2, Cy3, Cy5). Samples were run on 1824 cm gels, scanned with a Typhoon™ 9410 laser scanner and analysed in the DeCyder™ software. When selecting spots appearing only in triplicate (n = 1314), the mean error was 1.7 % (SD: 10.5 %; 95 % CI: 1.1-2.4 %). When setting the significance level to 99 %, no false-positive changes in protein volume ratios were detected. In the protocol presented here, only 0.5 mg tissue was used and separation of >2500 distinct protein spots in the pH range 3-11 and MW 10-200 kDa. Changes in protein abundance of <20 % could be detected. The method is especially useful when comparing muscle proteins between different conditions; for example, healthy and diseased tissue, before and after treatment or different exercise protocols.

  • 209.
    McLoon, Linda K.
    et al.
    University of Minnesota.
    Park, Han Na
    University of Minnesota.
    Kim, Jong-Hee
    University of Minnesota.
    Pedrosa-Domellof, Fatima
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Thompson, LaDora V.
    University of Minnesota.
    A continuum of myofibers in adult rabbit extraocular muscle: force, shortening velocity, and patterns of myosin heavy chain colocalization2011In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 111, no 4, p. 1178-1189Article in journal (Refereed)
    Abstract [en]

    Extraocular muscle (EOM) myofibers do not fit the traditional fiber typing classifications normally used in noncranial skeletal muscle, in part, due to the complexity of their individual myofibers. With single skinned myofibers isolated from rectus muscles of normal adult rabbits, force and shortening velocity were determined for 220 fibers. Each fiber was examined for myosin heavy chain (MyHC) isoform composition by densitometric analysis of electrophoresis gels. Rectus muscle serial sections were examined for coexpression of eight MyHC isoforms. A continuum was seen in single myofiber shortening velocities as well as force generation, both in absolute force (g) and specific tension (kN/m(2)). Shortening velocity correlated with MyHCIIB, IIA, and I content, the more abundant MyHC isoforms expressed within individual myofibers. Importantly, single fibers with similar or identical shortening velocities expressed significantly different ratios of MyHC isoforms. The vast majority of myofibers in both the orbital and global layers expressed more than one MyHC isoform, with up to six isoforms in single fiber segments. MyHC expression varied significantly and unpredictably along the length of single myofibers. Thus EOM myofibers represent a continuum in their histological and physiological characteristics. This continuum would facilitate fine motor control of eye position, speed, and direction of movement in all positions of gaze and with all types of eye movements-from slow vergence movements to fast saccades. To fully understand how the brain controls eye position and movements, it is critical that this significant EOM myofiber heterogeneity be integrated into hypotheses of oculomotor control.

  • 210. McLoon, Linda K.
    et al.
    Vicente, André
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Fitzpatrick, Krysta R.
    Lindström, Mona
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Pedrosa Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Composition, architecture, and functional implications of the connective tissue network of the extraocular muscles2018In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 1, p. 322-329Article in journal (Refereed)
    Abstract [en]

    Purpose: We examined the pattern and extent of connective tissue distribution in the extraocular muscles (EOMs) and determined the ability of the interconnected connective tissues to disseminate force laterally.

    Methods: Human EOMs were examined for collagens I, III, IV, and VI; fibronectin; laminin; and elastin using immunohistochemistry. Connective tissue distribution was examined with scanning electron microscopy. Rabbit EOMs were examined for levels of force transmission longitudinally and transversely using in vitro force assessment.

    Results: Collagens I, III, and VI localized to the endomysium, perimysium, and epimysium. Collagen IV, fibronectin, and laminin localized to the basal lamina surrounding all myofibers. All collagens localized similarly in the orbital and global layers throughout the muscle length. Elastin had the most irregular pattern and ran longitudinally and circumferentially throughout the length of all EOMs. Scanning electron microscopy showed these elements to be extensively interconnected, from endomysium through the perimysium to the epimysium surrounding the whole muscle. In vitro physiology demonstrated force generation in the lateral dimension, presumably through myofascial transmission, which was always proportional to the force generated in the longitudinally oriented muscles.

    Conclusions: A striking connective tissue matrix interconnects all the myofibers and extends, via perimysial connections, to the epimysium. These interconnections are significant and allow measurable force transmission laterally as well as longitudinally, suggesting that they may contribute to the nonlinear force summation seen in motor unit recording studies. This provides strong evidence that separate compartmental movements are unlikely as no region is independent of the rest of the muscle.

  • 211. Mercado, Jennifer Loh
    et al.
    Purvin, Valerie A
    Kawasaki, Aki
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    WuDunn, Darrell
    Bilateral sequential nonarteritic anterior ischemic optic neuropathy: a comparison of visual outcomes in fellow eyes using quantitative analysis of Goldmann visual fields2012In: Archives of ophthalmology (1960), ISSN 0003-9950, Vol. 130, no 7, p. 863-867Article in journal (Refereed)
    Abstract [en]

    Objective: To better define the concordance of visual loss in patients with nonarteritic anterior ischemic optic neuropathy (NAION).

    Methods: The medical records of 86 patients with bilateral sequential NAION were reviewed retrospectively, and visual function was assessed using visual acuity, Goldmann visual fields, color vision, and relative afferent papillary defect. A quantitative total visual field score and score per quadrant were analyzed for each eye using the numerical Goldmann visual field scoring method.

    Results: Outcome measures were visual acuity, visual field, color vision, and relative afferent papillary defect. A statistically significant correlation was found between fellow eyes for multiple parameters, including logMAR visual acuity (P=.01), global visual field (P <.001), superior visual field (P <.001), and inferior visual field (P <.001). The mean deviation of total (P <.001) and pattern (P <.001) deviation analyses was significantly less between fellow eyes than between first and second eyes of different patients.

    Conclusions: Visual function between fellow eyes showed a fair to moderate correlation that was statistically significant. The pattern of vision loss was also more similar in fellow eyes than between eyes of different patients. These results may help allow better prediction of visual outcome for the second eye in patients with NAION.

  • 212.
    Mönestam, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Asymptomatic capsular bag distension 10 years after cataract surgery2014In: JCRS Online Case Reports, ISSN 2214-1677, Vol. 2, no 3, p. 54-57Article in journal (Refereed)
    Abstract [en]

    Ten years after surgery, 120 patients who were part of a prospective longitudinal long-term study of cataract surgery outcome had a routine eye examination that included Scheimpflug photography (Pentacam HR). No patient had a previous posterior capsulotomy. Seven patients (6%) with distended capsular bags were found. None had experienced clinical symptoms. The distance between the intraocular lens (IOL) and the posterior capsule was between 300 μm and 740 μm. These cases suggest there is an asymptomatic timespan in cases with late-onset capsular bag distension syndrome. It is important to be aware of this syndrome when examining patients who had cataract surgery many years previously and no posterior capsulotomy. If there is a tendency for accumulation of fluid behind the IOL, most patients will need posterior capsulotomy within a few years, especially if the distance between the IOL and the posterior capsule is greater than 500 μm.

  • 213.
    Mönestam, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Frequency of Intraocular Lens Dislocation and Pseudophacodonesis, 20 Years After Cataract Surgery: A Prospective Study2019In: American Journal of Ophthalmology, ISSN 0002-9394, E-ISSN 1879-1891, Vol. 198, p. 215-222Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To examine the incidence and trends of late intraocular lens (IOL) dislocation/decentration and the frequency of pseudophakodonesis. DESIGN: Prospective, population-based cohort study. METHODS: A total of 800 patients were examined before cataract surgery in 1997-1998. Twenty years later, 100 of 133 survivors (75%) participated in the follow-up. An eye examination was performed including assessment for pseudophakodonesis and dislocation of the IOL. The medical records of all included patients at baseline were studied. Main outcome measures were previous IOL exchange or repositioning surgery, significant IOL dislocation, degree of pseudophakodonesis, and visual acuity. RESULTS: Twenty years after the original cataract surgery, 10 of the 800 patients at risk (1.2%) had needed dislocation surgery. Before cataract surgery, 39% of all patients had pseudoexfoliations (PXF). Mean time from cataract surgery to dislocation surgery was 12 years 6 months (range 3 years 9 months to 19 years 3 months). The cumulative incidence over 20 years was 6% in patients with PXF and 2% without PXF at surgery (P = .035). Mean age at cataract surgery in the 10 dislocated cases was 68.3 years (range 58-80). Twenty years after surgery, 5 of 98 (5%) patients had moderate/pronounced pseudophakodonesis. CONCLUSIONS: In this population-based cohort, the 20-year cumulative incidence of IOL dislocation needing surgical attention was significantly higher in patients with PXF than without PXF before surgery. The individual patient seems to have a low risk of being affected by this complication, but dislocated IOLs may cause a relatively large public health care burden, because of the large number of people in society with previous cataract surgery.

  • 214.
    Mönestam, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Long-term outcomes of cataract surgery: 15-year results of a prospective study2016In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 42, no 1, p. 19-26Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To describe the change over a 15-year period in corrected distance visual acuity (CDVA), subjective visual function, and neodymium:YAG (Nd:YAG) frequency after cataract surgery. SETTING: Eye Clinic, Norrlands University Hospital, Umea, Sweden. DESIGN: Prospective longitudinal population-based cohort study. METHODS: Patients who had cataract surgery during a 1-year period, 15 years previously (1997 to 1998), were included. All patients answered the same Visual Function-14 (VF-14) questionnaire preoperatively, 4 months postoperatively, and 5, 10, and 15 years after surgery. Most patients (88%; 168/190; 74% of survivors) also had an ocular examination. The CDVA was measured with logMAR charts. RESULTS: The study included 190 patients (83% of survivors). Fifteen years after surgery, the median CDVA in the operated eye had deteriorated from 20/20 postoperatively to 20/25 (P = .0001). Sixty percent of the patients had worsening of CDVA of less than 0.1 logMAR units compared with postoperatively. Fifty-four percent (103/190) had no deterioration in subjective visual function (VF-14), and 79% (150/190) had 10 points of decline or less. Previous Nd:YAG laser capsulotomy was more common in those younger than 65 years at surgery (49% versus 25%) (P = .002). CONCLUSIONS: The study confirms the effectiveness of cataract extraction, offering good long-term visual rehabilitation for the majority of the patients. The most common comorbidity causing large functional loss 15 years after surgery was age-related macular degeneration. Fifteen years after surgery, one half of the patients younger than 65 years at surgery had not required a posterior Nd:YAG laser capsulotomy. (C) 2016 ASCRS and ESCRS

  • 215.
    Mönestam, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Long-time outcome of cataract surgery-20 years results from a prospective study2018In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 9Article in journal (Other academic)
    Abstract [en]

    Purpose: This study reports the change, over a 20-year period, in best-corrected visual acuity (BCVA), subjective visual function (VF-14 questionnaire), and YAG-frequency after cataract surgery.

    Methods: This population-based prospective study reviewed 106 patients (79% of survivors), who underwent cataract surgery during a 1-year period 20 years previously (1997). All patients answered the same visual function questionnaire (VF-14) preoperatively, 4 months postoperatively, 5, 10, 15 and 20 years after surgery. Most patients (90%; 95/106; 70% of survivors) also had a routine ocular examination including BCVA and low contrast visual acuity (VA) 10% and 2.5%. Mean age at the time of surgery was 59 years (range 36-79) and 95% had a three-piece Acrysof® MA60BM implanted.

    Results: Twenty years after surgery the median BCVA of the operated eye had deteriorated to a median of 0.06 (logMAR) (Snellen acuity: 20/23) from 0.0 (logMAR) (20/20) postoperatively, (p=0.001). Sixty-one percent of the patients (58/95) had less than 0.1 logMAR units worsening of BCVA compared with postoperatively. Seventeen percent of the patients (16/95) had worse BCVA 20 years after surgery compared with the preoperative VA. Forty-two percent (45/106) had no deterioration in subjective visual function (VF-14), and mean VF-14 score 20 years after surgery was 92 (range 33-100). The majority of patients (78%;82/106) had 10 points decline or less and 6 percent of the patients (6/106) had a worsening of more than 30 points. 61% of the patients (58/95) had never had Nd:YAG laser capsulotomy. In 7% of the patients (7/95) no cataract surgery had occurred in the fellow eye.

    Conclusions: These prospective population-based, follow-up data provides estimates of extended long-term visual results. The effectiveness of cataract extraction, in offering good long-term visual rehabilitation for the majority of the patients, is confirmed. The extent and distribution of loss in subjective visual function is comparable to the outcome 10 and 15 years after surgery. Age-related macular degeneration remained the most common comorbidity causing large functional loss also 20 years after cataract surgery. Surprisingly, despite the low age at cataract surgery and the long time span, only a minority of patients had needed treatment for posterior capsular opacification.

  • 216.
    Mönestam, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Andersson, Mikael
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Åström, Siv
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Associations between subjective and objective visual function in patients with unilateral macular holes2008In: Vision Research, ISSN 0042-6989, E-ISSN 1878-5646, Vol. 48, no 1, p. 104-108Article in journal (Refereed)
    Abstract [en]

    Forty-six patients with uniocular macular holes and unaffected, fellow eyes were studied to evaluate inter- and intraocular associations between various objective tests of visual function and perceived visual ability. The affected eye had significant associations between visual acuity (VA) and the fovea threshold test, but for the fellow eye only VA and low-contrast VA 10% were associated. The reduction in visual acuity under low-contrast conditions relative to high-contrast did not differ between the affected eye and the healthy eye. Subjective visual ability seems to depend more on the visual acuity of the affected eye than the healthy eye.

  • 217.
    Mönestam, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Impact on visual function from light scattering and glistenings in intraocular lenses, a long-term study2011In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 89, no 8, p. 724-728Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the impact on visual function from light scattering and glistenings in intraocular lenses (IOLs) in patients who had cataract surgery 10 years previously. Setting: Eye clinic, Norrlands university hospital, Umeå, Sweden.

    Methods: One hundred and three patients, who had phacoemulsification with implantation of Acrysof((R)) MA60BM IOLs 10 years previously, were evaluated with best corrected visual acuity (VA), and low contrast visual acuity (LCVA) 10% and 2.5%. The light scattering from the IOLs was measured by Scheimpflug photography. The degree of glistenings was also quantified at the slit-lamp. Eyes with coexisting pathology that could affect VA and LCVA were excluded.

    Results: The patients were divided into various groups according to the degree of light scattering and grade of glistenings. In two subsets of patients, paired data from the patients' eyes were analysed. It was not possible to detect any significant impact on visual function, best corrected visual acuity (BCVA) and LCVA 10% and 2.5% in eyes with a more pronounced light scattering or a higher grade of glistenings seen at the slit-lamp. The correlation between IOL dioptric power and both the total light scattering of the IOL, and the subjective grading of the intensity of the glistenings at the slit-lamp was statistically significant (r(P) = 0.25; p = 0.012; r(S) = 0.23; p = 0.019, respectively).

    Conclusion: Most patients in this case series operated 10 years previously had severe glistenings and a high level of light scattering from their intraocular lenses. No detectable impact on BCVA, LCVA 10% and 2.5% was found.

  • 218.
    Mönestam, Eva I
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Incidence of dislocation of intraocular lenses and pseudophakodonesis 10 years after cataract surgery.2009In: Ophthalmology, ISSN 1549-4713, Vol. 116, no 12, p. 2315-2320Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To estimate the incidence of early and late intraocular lens (IOL) dislocation and the frequency of pseudophakodonesis in a population-based cohort of cataract surgery cases. The patients were followed up from before to 10 years after surgery. DESIGN: Cohort study. PARTICIPANTS: Eight hundred ten cataract surgery patients. METHODS: A prospective population-based cohort of 810 cataract surgery patients with presenile or senile cataracts was examined before surgery. Ten years later, 289 (73%) of 395 survivors agreed to participate in an eye examination. In addition to a routine eye examination of the anterior and posterior segment, all eyes were assessed for pseudophakodonesis and significant dislocation of the IOL. The medical records were studied and information concerning previous postoperative surgical interventions such as IOL exchange or repositioning was noted. This information was also obtained from the records of the deceased patients and those unable or unwilling to participate. The material was analyzed statistically. MAIN OUTCOME MEASURES: Previous IOL exchange or repositioning surgery, significant IOL dislocation, and degree of pseudophakodonesis. RESULTS: Most patients (n = 795/810; 98%) underwent sutureless clear corneal phacoemulsification surgery with a 3.2-mm temporal incision. A foldable IOL was implanted, 95% of which were an Alcon MA60BM AcrySof (Alcon Inc, Fort Worth, TX). Approximately 40% of the patients had pseudoexfoliations (PEX). After a 10-year follow-up, 5 (0.6%) of the 800 patients at risk required surgery for a dislocated IOL. All of these patients were male, and in all cases, the dislocation was late and within the capsular bag. The cumulative incidence over 10 years was 1%. At the examination 10 years after surgery, 2 (0.7%) of 287 patients at risk had pronounced pseudophakodonesis and 4 (1.4%) had moderate pseudophakodonesis. CONCLUSIONS: The 10-year cumulative incidence of dislocated IOLs needing surgical attention was low in this population-based cohort with a high frequency of PEX. Early dislocation did not occur in any of the patients. The risk of this complication in an individual patient seems to be low. Because of the large number of people with previous cataract surgery, dislocated IOLs may cause a relatively large public health care burden.

  • 219.
    Mönestam, Eva I
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lundqvist, Britta
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Extended long-term outcomes of cataract surgery2011In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 90, no 7, p. 651-656Article in journal (Refereed)
    Abstract [en]

    Purpose:  To longitudinally report the changes in visual acuity (VA) and subjective visual function, 10 years after cataract surgery.

    Methods: This population-based prospective study reviewed 335 patients (85% of survivors) who underwent cataract surgery during a 1-year period in 1997-98, 289 of whom were also re-examined. The patients underwent a routine eye examination and answered the same visual function questionnaire (VF-14), preoperatively, 4 months postoperatively, 5 years and 10 years after surgery.

    Results: Ten years after surgery, the best corrected VA (BCVA) of the operated eye had deteriorated to a median of 0.06 (logMAR) (Snellen acuity: 20/23) from 0.046 (logMAR) (20/22) postoperatively (p = 0.001). More than two-thirds of the patients had <0.1 logMAR units worsening of BCVA compared with postoperatively. Approximately half of the patients had no deterioration in subjective visual function, and 77% had 10 points decline or less. Twelve per cent of the patients (42/335) had a worsening of more than 30 points. Effect size was calculated for the VF-14 total score at all three occasions of follow-up after surgery and was largest approximately 4 months postoperatively. Long-time follow-up of 10 years shows still moderate effect size.

    Conclusion: These results confirm the effectiveness of cataract extraction, offering good long-term visual rehabilitation for the majority of the patients. The most common cause for large functional loss after 10 years is age-related macular degeneration.

  • 220.
    Mönestam, Eva I
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lundqvist, Britta M
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Jonsson, Åsa C
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Long-time visual functional results of cataract surgery on low vision patients2008In: Clinical ophthalmology (Auckland, N.Z.), ISSN 1177-5467, Vol. 2, no 1, p. 187-194Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIMS: To assess longitudinal 5-year results of cataract surgery on low vision patients. METHODS: In this prospective, long-time, observational case-series, we report the outcome regarding the subjective visual function (n = 35) assessed by a visual function questionnaire (VF-14) and the visual acuity (n = 30) of surviving low vision patients 5 years after surgery. We compare with data recorded on the same patients before surgery and 4 months postoperatively. RESULTS: Five years after surgery, 57% had unchanged or better VF-14 score compared with preoperatively, and 37% compared with postoperatively. Maculopathy patients had a significantly larger deterioration 5 years after surgery compared with postoperatively (40.2 versus 51.7, p = 0.004), but for the glaucoma patients there was no significant change (52.6 versus 53.1). There were no significant associations between age of the patient and change in VF-14 score or change in visual acuity 5 years after surgery, neither compared with before surgery nor postoperatively. CONCLUSION: Results suggest a favorable functional outcome 5 years after cataract surgery on most low-vision patients. Glaucoma patients have a more stable outcome than patients with macular degeneration. The severity of the disease-process for each individual patient might be the most important factor affecting the long-time results.

  • 221.
    Mönestam, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lundquist, B
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Wachtmeister, Lillemor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Visual function and car driving: longitudinal results 5 years after cataract surgery in a population2005In: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079, Vol. 89, no 4, p. 459-463Article in journal (Refereed)
    Abstract [en]

    Aims: To determine visual function in drivers who had cataract surgery 5 years previously, and to analyse longitudinal data, by comparing preoperative and postoperative changes in subjective driving ability and objective visual function.

    Methods: All patients (810) who underwent cataract surgery, during a 1 year period, were prospectively studied. Data regarding present driving status were collected from self administered questionnaires and visual acuity (VA) data were measured before and after surgery. All patients who were alive 5 years later were invited to participate with a new eye examination and questionnaire.

    Results: Before surgery 36 active drivers (16%) did not fulfil the visual requirements for driving; with improved glasses this number could be reduced to 24 (11%). 5 years after surgery, the corresponding figures were 5% and 3% (5/174), respectively. Before surgery 50% stated visual difficulties while driving in daylight and 79% in darkness. A few months and 5 years after surgery the corresponding figures were 6% and 5%, respectively, for daytime driving and 34% and 44%, respectively, for night-time driving.

    Conclusions: Long term results regarding cataract surgery in car drivers are beneficial. 5 years after surgery only a few patients drove not fulfilling the requirements, but there were a larger proportion of patients with problems driving in darkness compared with a few months after surgery.

  • 222.
    Mönestam, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lundqvist, Britta
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Long-term visual outcome after cataract surgery: Comparison of healthy eyes and eyes with age-related macular degeneration.2012In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 38, no 3, p. 409-414Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To compare the long-term longitudinal visual acuity outcomes after cataract surgery in eyes with age-related macular degeneration (AMD) at surgery and eyes without comorbidity. SETTING: University-based eye clinic. DESIGN: Longitudinal cohort study. METHODS: Patients having cataract surgery were evaluated over 1 year. A clinical eye examination and corrected distance visual acuity (CDVA) measurement were performed preoperatively and postoperatively as well as 5 and 10 years postoperatively for eligible patients. The patients were divided into functional groups depending on postoperative signs of macular degeneration and postoperative CDVA. RESULTS: The study evaluated 810 patients. The rate of CDVA decline with age was faster in AMD patients than in patients without comorbidity. The slope of the visual acuity decline was similar in the 2 subgroups with AMD (almost normal CDVA and reduced CDVA postoperatively). After adjustment for age, there was a mean loss of 2.3 logMAR letters in patients with no comorbidity and 6.4 letters in patients with AMD at surgery for each decade of increasing age. More than 75% of AMD patients had better CDVA 10 years after surgery than before surgery. CONCLUSIONS: Patients with signs of AMD at cataract surgery had a longitudinally worse visual outcome than patients without clinical signs of AMD. However, there is no reason to discourage patients with concurrent visually significant cataract and AMD from having surgery because most AMD patients had better CDVA 10 years after surgery than before surgery. FINANCIAL DISCLOSURE: Neither author has a financial or proprietary interest in any material or method mentioned.

  • 223.
    Mönestam, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lundqvist, Britta
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Long-time results and associations between subjective visual difficulties with car driving and objective visual function 5 years after cataract surgery2006In: J Cataract Refract Surg, Vol. 32, no 1, p. 50-55Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To determine results and associations between subjective visual difficulties while driving and objective visual function in drivers who had cataract surgery 5 years previously. SETTING: Norrlands University Hospital, Umeå, Sweden. METHODS: This prospective outcomes study examined 189 active drivers who had cataract surgery 5 years earlier. Visual acuity and low-contrast visual acuity (LCVA) were measured, and a questionnaire with driving-specific questions (VF-14 based) was completed. The results were compared with data before and after surgery. RESULTS: Five years after cataract surgery, only a small proportion of patients (3%) drove without fulfilling the visual requirements. Few patients (5%) reported visual difficulties while driving in daylight, but a large proportion (43%) experienced difficulties in darkness, with glare being the most common problem. There was a statistically significant association between an LCVA of less than 20/50 and reporting subjective visual difficulties while driving (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.1 to 6.8). Women had 1.8 times the odds of reporting visual difficulties compared with men (95% CI, 1.0 to 3.5). CONCLUSIONS: Most active drivers had excellent visual acuity and no difficulty with daytime driving and distance estimation 5 years after cataract surgery. A large proportion of patients experienced difficulties while driving at night. These data suggest an adjusted association between LCVA and self-assessed visual difficulties while driving 5 years after cataract surgery. Our data confirm the importance of LCVA in relation to driving, especially in darkness.

  • 224.
    Mönestam, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Wachmeister, Lillemor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Impact of cataract surgery on the visual ability of the very old2004In: American Journal of Ophthalmology, ISSN 0002-9394, E-ISSN 1879-1891, Vol. 137, no 1, p. 145-155Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To compare the functional outcome of cataract surgery in terms of visual ability between patients ages younger than 84 years, 85 to 89 years, and 90+ years. Survival time will be estimated at 4 years. DESIGN: Population-based, observational case series. METHODS: We prospectively evaluated elderly cataract patients' self-assessed visual ability regarding reading, TV viewing, orientation ability, activities of daily life, satisfaction, and visual acuity (VA) before and approximately 3 months after cataract surgery. All patients operated on during a 1-year period from our geographically defined admitting area that participated with a questionnaire were included (n = 837). Survival was checked after 4 years. RESULTS: Before surgery, the most elderly were significantly more dissatisfied with their visual function (P =.007). Seventy-six percent of 85+ improved their subjective ability to read, and two-thirds of those unable to read newspaper print were able to read after surgery. A total of 79% of 90+ experienced improved postoperative ability to manage their daily lives. Best-corrected VA (BCVA) improved in 94% (90+ years of age), 90% (85 to 89 years of age), and 97% (younger than 84 years of age), respectively. After surgery, VA was significantly worse with increasing age, also after adjustment for ocular comorbidity (P <.0001). Patients with a BCVA improvement of less than 0.3 logarithm of the minimal angle of resolution units, patients with comorbidity, and patients aged 90+ had approximately 3 times the odds of being dissatisfied with vision after surgery. A total of 43% of 90+ years and 62% of 85 to 89 years were alive 4 years after surgery. CONCLUSIONS: Most patients aged 85 and older had improved visual ability, acuity, and satisfaction after cataract surgery. In terms of visual function, surgery of significant cataracts in the very old is beneficial also when life expectancy is taken in account.

  • 225.
    Mönestam, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Wachtmeister, Lillemor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Change of subjective visual function in first-eye cataract patients when the rate of surgery increases in a population.2002In: Medical Care, ISSN 0025-7079, E-ISSN 1537-1948, Vol. 40, no 11, p. 1080-1089Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The increasing demand for cataract surgery has stimulated interest in outcome research and the potential public health impact of the intervention. OBJECTIVE: To determine the impact of an increased rate of first-eye cataract surgery on visual acuity (VA) and subjective visual ability/disability, before and after surgery, in a geographically defined population. RESEARCH DESIGN: A prospective, observational study. SUBJECTS: All patients who had first-eye cataract extraction at one clinic during two separate 1-year periods. Five hundred seventy-six patients had surgery in 1997, and 353 had surgery in 1992 (17.2 and 10.6 per 1000 population 65 and older, respectively). MEASURES: Best-corrected VAs were measured, and the patients answered self-administered questionnaires, before and after surgery. The questionnaires focused on the patients' subjective difficulties performing some common vision-dependent activities, such as reading, television-viewing, orientation, etc. RESULTS: In 1997 compared with 1992 the VA of the eye to be operated was on average better (chi2 for trend; P<0.0001), and the subjective visual disability was less before surgery (mean disability index 6.9 vs. 7.5; P<0.0001). There was also a smaller percentage of mature cataracts (15% vs. 23%; P<0.0001). After surgery the VA of the operated eye was better in 1997 (chi2 for trend; P<0.001), but there was no difference in improvement of subjective visual ability, nor change in subjective visual disability, compared with 1992. The patients' expectations and actual postoperative improvement of their ability to cope with daily life were higher in 1997 (chi2 for trend; P<0.0001 and P<0.001). CONCLUSIONS: A higher frequency of first-eye cataract surgery in a population was before surgery associated with an on average better VA of the eye to be operated, a less perceived visual disability regarding some common vision-dependent activities, a lower percentage of mature cataracts and thus earlier surgery. Consequently, a higher rate of surgery would likely be associated with a lesser amount of visual impairment because of cataract in the population.

  • 226. Münch, Mirjam
    et al.
    Kawasaki, Aki
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Intrinsically photosensitive retinal ganglion cells: classification, function and clinical implications2013In: Current Opinion in Neurology, ISSN 1350-7540, E-ISSN 1473-6551, Vol. 26, no 1, p. 45-51Article, review/survey (Refereed)
    Abstract [en]

    Purpose of review The discovery of a new class of intrinsically photosensitive retinal ganglion cells (ipRGCs) revealed their superior role for various nonvisual biological functions, including the pupil light reflex, and circadian photoentrainment. Recent findings Recent works have identified and characterized several anatomically and functionally distinct ipRGC subtypes and have added strong new evidence for the accessory role of ipRGCs in the visual system in humans. Summary This review summarizes current concepts related to ipRGC morphology, central connections and behavioural functions and highlights recent studies having clinical relevance to ipRGCs. Clinical implications of the melanopsin system are widespread, particularly as related to chronobiology.

  • 227. Münch, Mirjam
    et al.
    Léon, Lorette
    Crippa, Sylvain V
    Kawasaki, Aki
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Circadian and wake-dependent effects on the pupil light reflex in response to narrow-bandwidth light pulses2012In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 53, no 8, p. 4546-4555Article in journal (Refereed)
    Abstract [en]

    Purpose. Nonvisual light-dependent functions in humans are conveyed mainly by intrinsically photosensitive retinal ganglion cells, which express melanopsin as photopigment. We aimed to identify the effects of circadian phase and sleepiness across 24 hours on various aspects of the pupil response to light stimulation.

    Methods. We tested 10 healthy adults hourly in two 12-hour sessions covering a 24-hour period. Pupil responses to narrow bandwidth red (635 ± 18 nm) and blue (463 ± 24 nm) light (duration of 1 and 30 seconds) at equal photon fluxes were recorded, and correlated with salivary melatonin concentrations at the same circadian phases and to subjective sleepiness ratings. The magnitude of pupil constriction was determined from minimal pupil size. The post-stimulus pupil response was assessed from the pupil size at 6 seconds following light offset, the area within the redilation curve, and the exponential rate of redilation.

    Results. Among the measured parameters, the pupil size 6 seconds after light offset correlated with melatonin concentrations (P < 0.05) and showed a significant modulation over 24 hours with maximal values after the nocturnal peak of melatonin secretion. In contrast, the post-stimulus pupil response following red light stimulation correlated with subjective sleepiness (P < 0.05) without significant changes over 24 hours.

    Conclusions. The post-stimulus pupil response to blue light as a marker of intrinsic melanopsin activity demonstrated a circadian modulation. In contrast, the effect of sleepiness was more apparent in the cone contribution to the pupil response. Thus, pupillary responsiveness to light is under influence of the endogenous circadian clock and subjective sleepiness.

  • 228. Nilipour, Y.
    et al.
    Nafissi, S.
    Tjust, Anton E.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Ravenscroft, G.
    Hossein Nejad Nedai, H.
    Taylor, R. L.
    Varasteh, V.
    Pedrosa Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Zangi, M.
    Tonekaboni, S. H.
    Olivé, M.
    Kiiski, K.
    Sagath, L.
    Davis, M. R.
    Laing, N. G.
    Tajsharghi, H.
    Ryanodine receptor type 3 (RYR3) as a novel gene associated with a myopathy with nemaline bodies2018In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 25, no 6, p. 841-847Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Nemaline myopathy (NEM) has been associated with mutations in 12 genes to date. However, for some patients diagnosed with NEM, definitive mutations are not identified in the known genes, suggesting that there are other genes involved. This study describes compound heterozygosity for rare variants in ryanodine receptor type 3 (RYR3) gene in one such patient.

    METHODS AND RESULTS: Clinical examination of the patient at 22 years of age revealed a long narrow face, high arched palate and bilateral facial weakness. She had proximal weakness in all four limbs, mild scapular winging but no scoliosis. Muscle biopsy revealed wide variation in fibre size with type 1 fibre predominance and atrophy. Abundant nemaline bodies were located in perinuclear and subsarcolemmal areas, and within the cytoplasm. No likely pathogenic mutations in known NEM genes were identified. Copy number variation in known NEM genes was excluded by NEM-targeted comparative genomic hybridization array. Next-generation sequencing revealed compound heterozygous missense variants in the RYR3 gene. RYR3 transcripts are expressed in human fetal and adult skeletal muscle as well as in human brain and cauda equina samples. Immunofluorescence of human skeletal muscle revealed a 'single-row' appearance of RYR3, interspersed between the 'double rows' of ryanodine receptor type 1 (RYR1) at each A-I junction.

    CONCLUSION: The results suggest that variants in RYR3 may cause a recessive muscle disease with pathological features including nemaline bodies. We characterize the expression pattern of RYR3 in human skeletal muscle and brain, and the subcellular localization of RYR1 and RYR3 in human skeletal muscle.

  • 229.
    Nilsson, Emma C
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Storm, Rickard J
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Bauer, Johannes
    University of Tübingen.
    Johansson, Susanne M C
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Lookene, Aivar
    Tallinn University of Technology, Tallinn, Estonia..
    Ångström, Jonas
    University of Göteborg.
    Hedenström, Mattias
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Eriksson, Therese L
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Frängsmyr, Lars
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Rinaldi, Simon
    University of Glasgow.
    Willison, Hugh J
    University of Glasgow.
    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.
    Stehle, Thilo
    University of Tübingen, Vanderbilt University School of Medicine.
    Arnberg, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    The GD1a glycan is a cellular receptor for adenoviruses causing epidemic keratoconjunctivitis (Letter)2011In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 17, no 1, p. 105-109Article in journal (Refereed)
    Abstract [en]

    Adenovirus type 37 (Ad37) is a leading cause of epidemic keratoconjunctivitis (EKC), a severe and highly contagious ocular disease. Whereas most other adenoviruses infect cells by engaging CD46 or the coxsackie and adenovirus receptor (CAR), Ad37 binds previously unknown sialic acid-containing cell surface molecules. By glycan array screening, we show here that the receptor-recognizing knob domain of the Ad37 fiber protein specifically binds a branched hexasaccharide that is present in the GD1a ganglioside and that features two terminal sialic acids. Soluble GD1a glycan and GD1a-binding antibodies efficiently prevented Ad37 virions from binding and infecting corneal cells. Unexpectedly, the receptor is constituted by one or more glycoproteins containing the GD1a glycan motif rather than the ganglioside itself, as shown by binding, infection and flow cytometry experiments. Molecular modeling, nuclear magnetic resonance and X-ray crystallography reveal that the two terminal sialic acids dock into two of three previously established sialic acid-binding sites in the trimeric Ad37 knob. Surface plasmon resonance analysis shows that the knob-GD1a glycan interaction has high affinity. Our findings therefore form a basis for the design and development of sialic acid-containing antiviral drugs for topical treatment of EKC.

  • 230.
    Nordström, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Schiller, Maria
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Fredriksson, Anneli
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Refractive improvements and safety with topography-guided corneal crosslinking for keratoconus: 1-year results2017In: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079, Vol. 101, no 7, p. 920-925Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To assess the refractive improvements and the corneal endothelial safety of an individualised topography-guided regimen for corneal crosslinking in progressive keratoconus.

    METHODS: An open-label prospective randomised clinical trial was performed at the Department of Clinical Sciences, Ophthalmology, Umeå University Hospital, Umeå, Sweden. Thirty-seven patients (50 eyes) with progressive keratoconus planned for corneal crosslinking were included. The patients were randomised to topography-guided crosslinking (photorefractive intrastromal crosslinking (PiXL); n=25) or uniform 9 mm crosslinking (corneal collagen crosslinking (CXL); n=25). Visual acuity, refraction, keratometry (K1, K2 and Kmax) and corneal endothelial morphometry were assessed preoperatively and at 1, 3, 6 and 12 months postoperatively. The PiXL treatment involved an asymmetrical treatment zone centred on the area of maximum corneal steepness with treatment energies ranging from 7.2 to 15.0 J/cm(2); the CXL treatment was a uniform 9 mm 5.4 J/cm(2) pulsed crosslinking. The main outcome measures were changes in refractive errors and corneal endothelial cell density.

    RESULTS: The spherical refractive errors decreased (p<0.05) and the visual acuity improved (p<0.01) at 3, 6 and 12 months after PiXL, but not after CXL. The between-groups differences, however, were not significant. K2 and Kmax decreased at 3, 6 and 12 months after PiXL (p<0.01), but not after CXL (p<0.01 when comparing the two treatments). No corneal endothelial cell loss was seen after either treatment.

    CONCLUSIONS: Individualised topography-based crosslinking treatment centred on the ectatic cone has the potential to improve the corneal shape in keratoconus with decreased spherical refractive errors and improved visual acuity, without damage to the corneal endothelium.

  • 231.
    Nyström, Alexander
    et al.
    Department of Experimental Medical Science, Division for Cell and Matrix Biology, Lund University.
    Holmblad, Johanna
    Department of Experimental Medical Science, Division for Cell and Matrix Biology, Lund University.
    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.
    Sasaki, Takako
    Max-Planck-Institut für Biochemie, Martinsried, Germany.
    Durbeej, Madeleine
    Department of Experimental Medical Science, Division for Cell and Matrix Biology, Lund University.
    Extraocular muscle is spared upon complete laminin alpha2 chain deficiency: comparative expression of laminin and integrin isoforms.2006In: Matrix Biology, ISSN 0945-053X, E-ISSN 1569-1802, Vol. 25, no 6, p. 382-385Article in journal (Refereed)
    Abstract [en]

    Mutations in the gene encoding laminin (LM) alpha2 chain cause congenital muscular dystrophy. Here, we show that extraocular muscle (EOM) is spared upon complete LMalpha2 chain absence. The major LM chains in limb muscle basement membranes are alpha2, beta1, beta2 and gamma1 whereas alpha2, alpha4, beta1, beta2 and gamma1 chains are expressed in EOM. Expression of LMalpha4 chain mRNA is further increased in LMalpha2 chain deficient EOM. Mainly integrin alpha7X1 subunit, which binds to laminin-411, is expressed in EOM and in contrast to dystrophic limb muscle, sustained integrin alpha7B expression is seen in LMalpha2 chain deficient EOM. We propose that LMalpha4 chain, possibly by binding to integrin alpha7BX1beta1D, protects EOM in LMalpha2 chain deficient muscular dystrophy.

  • 232.
    Näslund, Sofie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Photorefractive intrastromal crosslinking as a treatment for low-grade myopia Comparison of two UV illumination protocols2018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 233. Ohira, Akihiro
    et al.
    Hara, Katsunori
    Johannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Tanito, Masaki
    Asgrimsdottir, Gudrun Marta
    Lund, Sigrun H.
    Loftsson, Thorsteinn
    Stefansson, Einar
    Topical dexamethasone -cyclodextrin nanoparticle eye drops increase visual acuity and decrease macular thickness in diabetic macular oedema2015In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 93, no 7, p. 610-615Article in journal (Refereed)
    Abstract [en]

    PurposeTo compare in a randomized, controlled trial topical 1.5% dexamethasone -cyclodextrin nanoparticle eye drops (DexNP) with posterior subtenon injection of triamcinolone acetonide in diabetic macular oedema (DME). MethodsIn this prospective, randomized, controlled trial, 22 eyes of 22 consecutive patients with DME were randomized to (i) topical treatment with DexNP x3/day (4weeks), x2/day (4weeks) and x1/day (4weeks) or (ii) one posterior subtenon injection of 20mg triamcinolone acetonide. Study visits were at baseline and 4, 8, 12 and 16weeks. ResultsThe logMAR (Snellen) visual acuity (meanSD) improved significantly with DexNP from 0.41 +/- 0.3 (Snellen 0.39) to 0.32 +/- 0.25 (0.48) and 0.30 +/- 0.26 (0.50) at 4 and 8weeks, respectively. One-third of the DexNP group improved more than 0.3 logMAR units. For triamcinolone, logMAR changed significantly from 0.42 +/- 0.28 (0.38) at baseline to 0.32 +/- 0.29 (0.48) at 4w and 0.33 +/- 0.37 (0.47) at 12w. The central macular thickness (CMT) decreased significantly with DexNP from 483 +/- 141m to 384 +/- 142m at 4w and 342 +/- 114m at 8w. For triamcinolone, CMT decreased significantly at all time-points: 494 +/- 94m, 388 +/- 120, 388 +/- 145, 390 +/- 136 and 411 +/- 104m at 0, 4, 8, 12 and 16weeks, respectively. There was a modest increase in intraocular pressure (IOP) at all time-points with DexNP while no increase was seen with triamcinolone. Serum cortisol was affected by both treatments. ConclusionTopical DexNP significantly improve visual acuity and decrease macular thickness in patients with DME. The effect is similar to that from subtenon triamcinolone. A modest increase in IOP was seen with the nanoparticle eye drops, but IOP normalized after the discontinuation of treatment.

  • 234.
    Ohira, Akihiro
    et al.
    Izumo, Japan.
    Hara, Katsunori
    Izumo, Japan.
    Johannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Tanito, Masaki
    Izumo, Japan.
    Asgrimsdottir, Gudrun Marta
    Reykjavik, Iceland.
    Lund, Sigrun H.
    Reykjavik, Iceland.
    Loftsson, Thorsteinn
    Reykjavik, Iceland.
    Stefansson, Einar
    Reykjavik, Iceland.
    Topical Dexamethasone gamma-Cyclodextrin Nanoparticle Eye Drops increase Visual Acuity and decrease Macular Thickness in Diabetic Macular Edema2015In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 56, no 7, article id 2289Article in journal (Other academic)
    Abstract [en]

    Purpose: To test the efficacy and safety of topical 1.5% dexamethasone γ-cyclodextrin nanoparticle eye drops (dexNP) for diabetic macular edema (DME) and compare to posterior subtenon injection of triamcinolone acetonide.

    Methods: This was a prospective, randomized controlled trial with 22 eyes in 22 consecutive patients with DME, who were randomized to a) topical treatment with dexNP eye drops x3/day for one month, x2/day the next month and finally x1/day the third month or b) one posterior subtenon injection of 20mg triamcinolone acetonide.

    Results: The central macular thickness (CMT) decreased significantly with dexNP eye drops from 483±141mm to 384±142 mm at 4 weeks and 342±114 mm at 8 weeks. For triamcinolone, CMT decreased significantly at all time points. Visual acuity (logMAR) improved significantly with dexNP eye drops from 0.41±0.3 (mean±SD) to 0.32±0.25 and 0.30±0.26 at 4 and 8 weeks respectively. One third of the eye drop group improved more than 0.3 logMAR units. For triamcinolone, logMAR changed significantly from 0.42±0.28 at baseline to 0.32±0.29 at 4 weeks and 0.33±0.37 at 12 weeks. There was a modest increase in IOP at all time points with dexNP eye drops while no increase was seen with triamcinolone. Serum cortisol was affected by both treatments.

    Conclusions: Topical dexamethasone γ-cyclodextrin nanoparticle eye drops significantly improve visual acuity and decrease macular thickness in patients with DME. The effect is similar to that from subtenon triamcinolone as well as to reports on intravitreal steroid implants and triamcinolone intravitreal injections. A modest increase in IOP was seen with the nanoparticle eye drops but IOP normalized after discontinuation of treatment.

  • 235.
    Olofsson, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Superoxide dismutase 1 and cataract2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Light and oxygen generate harmful reactive oxygen species (ROS) in the lens, causing biochemical changes that gradually disarrange the lens fibres resulting in light scattering and loss of transparency. In the healthy eye, this chronic exposure to oxidative stress may lead to age-related cataract. However, there are also some conditions that accelerate cataract formation, such as diabetes mellitus, in which increased glucose levels may contribute to increased generation of ROS.

    The superoxide dismutases (SOD) participate in the defence against ROS by catalysing the dismutation of superoxide radicals. The main SOD isoenzyme in the lens is copper-zinc superoxide dismutase (SOD1). The aim of this thesis was to explore if this antioxidant enzyme is important for the protection against age-related and diabetes-induced cataract development.

    Lenses from wild-type mice and mice lacking SOD1 were incubated in high levels of glucose in vitro and their transparency and damage evaluated daily. Also, the impact of nitric oxide was studied by adding a nitric oxide synthase inhibitor. Furthermore, in vivo cataract formation in relation to the oxidative status of the lens was evaluated in streptozotocin-induced diabetic mice as well as in non-diabetic mice of both genotypes. Finally, the spontaneous age-related cataract development was studied in both genotypes.

    In vitro, the SOD1 null lenses showed increased levels of superoxide radicals and developed dense nuclear lens opacities upon exposure to high levels of glucose. They also showed increased lens leakage of lactate dehydrogenase, reduced transport function across cell membranes, and increased water contents. However, the lens damage and cataract formation were eliminated when the synthesis of nitric oxide was inhibited. This indicates that both superoxide and nitric oxide have important roles in glucose-induced cataract development possibly through their reaction with each other which generates the highly reactive peroxynitrite.

    In vivo, both the SOD1 null and the wild-type mice showed cortical cataract changes after 8 weeks of diabetes, although the SOD1 null mice showed a more pronounced cataract formation than the wild-type mice in relation to the level of hyperglycaemia. As cataract formation was accentuated the lenses showed diminishing levels of glutathione but increasing amounts of protein carbonyls, suggesting a reduced lens antioxidant capacity as well as increased lens protein oxidation. Non-diabetic young (18 weeks of age) SOD1 null mice did not show any signs of cataract. At 1 year of age they had developed some cortical lens obscurity as compared to the wild-type mice which did not show equivalent changes until 2 years of age.

    The results presented in this thesis show that SOD1 null mice are more prone to develop diabetes-induced and age-related cataract than wild-type mice. The findings thus further endorse the importance of oxidative stress as a contributor to cataract development and indicate that both superoxide and nitric oxide may be damaging to the lens. I therefore conclude that the antioxidant enzyme SOD1 is important for the protection against cataract.

  • 236.
    Olofsson, Eva M
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Marklund, Stefan L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Enhanced diabetes-induced cataract in copper-zinc superoxide dismutase-null mice2009In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 50, no 6, p. 2913-2918Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Oxidative stress is thought to contribute to diabetes-induced cataract, and the authors have previously demonstrated that lenses from mice lacking the antioxidant enzyme copper-zinc superoxide dismutase (SOD1) show elevated levels of superoxide radicals and are more prone in vitro to develop glucose-induced cataract than are wild-type lenses. In the present study the effect of streptozotocin-induced diabetes mellitus on cataract formation in SOD1-null and wild-type mice in vivo was examined.

    METHODS: Eight weeks after diabetes was established by repeated intraperitoneal streptozotocin injections, the mice were killed and the lenses removed and photographed in retroillumination. The cataract was quantified from the photographs by digital image analysis and the lens contents of glutathione (GSH) as well as the lens protein carbonyl contents suggestive of protein oxidation were analyzed.

    RESULTS: The streptozotocin-induced diabetic SOD1-null mice developed more cataract than the diabetic wild-type mice. Also, lens GSH levels were lower in the diabetic SOD1-null mice than in the nondiabetic SOD1-null mice. However, the protein carbonyls were equally raised in the diabetic mice of both genotypes.

    CONCLUSIONS: The increased cataract formation and the compromised antioxidant capacity found in the diabetic SOD1-null lenses thus emphasize the involvement of superoxide radicals in diabetes-induced cataract.

  • 237.
    Olofsson, Eva M
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Marklund, Stefan L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Glucose-induced cataract in CuZn-SOD null lenses: an effect of nitric oxide?2007In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 42, no 7, p. 1098-1105Article in journal (Refereed)
    Abstract [en]

    Lenses from mice lacking the antioxidant enzyme copper-zinc superoxide dismutase (SOD1) show elevated levels of superoxide radicals and are prone to developing cataract when exposed to high levels of glucose in vitro. As superoxide may react further with nitric oxide, generating cytotoxic reactive nitrogen species, we attempted to evaluate the involvement of nitric oxide in glucose-induced cataract. Lenses from SOD1-null and wild-type mice were incubated with high or normal levels of glucose (55.6 and 5.56 mM). A nitric oxide synthase inhibitor (L-NAME) or a nitric oxide donor (DETA/NO) was added to the culture medium. Cataract development was assessed using digital image analysis of lens photographs and cell damage by analyzing the leakage of lactate dehydrogenase. The levels of superoxide radicals in the lenses were also measured. L-NAME was found to reduce cataract development and cell damage in the SOD1-null lenses exposed to high glucose. On the other hand, DETA/NO accelerated cataract development, especially in the SOD1-null lenses. These lenses also showed a higher leakage of lactate dehydrogenase than wild-type controls. We conclude that a combination of high glucose and absence of SOD1 increases the formation of cataract and that nitric oxide probably contributes to this process.

  • 238.
    Olofsson, Eva M
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Marklund, Stefan L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Karlsson, Kurt
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    In vitro glucose-induced cataract in copper-zinc superoxide dismutase null mice2005In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 81, no 6, p. 639-646Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to evaluate the involvement of the superoxide radical in glucose-induced cataract using lenses from mice lacking the cytosolic copper-zinc superoxide dismutase (SOD1). Lenses from wild-type mice and SOD1 null mice were kept in organ culture with either 5.6 or 55.6 mM glucose for 6 days. The cataract formation was followed with digital image analysis and ocular staging. The lens damage was further quantified by analysis of the leakage of lactate dehydrogenase into the medium by the uptake of 86Rb and by determining the water content of the lenses. The formation of superoxide radicals in the lenses was assessed with lucigenin-derived chemiluminescence. Immunohistochemical staining for SOD1 was also performed on murine lenses. The SOD1 null lenses exposed to high glucose developed more cataract showed an increased leakage of lactate dehydrogenase and developed more oedema compared to the control lenses. At 5.6 mM glucose there was no difference between the SOD1 null and wild-type lenses. Staining for SOD1 was seen primarily in the cortex of the wild-type lens. This in vitro model suggests an involvement of the superoxide radical and a protective effect of SOD1 in glucose-induced cataract formation.

  • 239.
    Olofsson, Eva M
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Marklund, Stefan L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Interleukin-1alpha downregulates extracellular-superoxide dismutase in human corneal keratoconus stromal cells2007In: Molecular Vision, ISSN 1090-0535, E-ISSN 1090-0535, Vol. 13, p. 1285-1290Article in journal (Other academic)
    Abstract [en]

    PURPOSE: The purpose of this investigation was to elucidate the regulation of corneal extracellular superoxide dismutase (SOD3) synthesis in keratoconus. We compared the basal and cytokine-regulated SOD3 synthesis in cultured human stromal cells from keratoconus corneas to stromal cells from normal and bullous keratopathy corneas.

    METHODS: Keratocyte cultures were obtained from patients undergoing corneal transplantation for keratoconus and bullous keratopathy, and from healthy donor corneas. The cell lines obtained were cultured until near confluence and interleukin-1alpha, interleukin-6, transforming growth factor beta, or platelet derived growth factor were added to the media. The phenotypes of the cultured cells were assessed by immunocytochemical expression of alpha-smooth muscle actin and CD34. SOD3 protein contents were determined in the culture media with ELISA after 24, 48, 72, and 96 h.

    RESULTS: Interleukin-1alpha had an inhibitory effect on SOD3 synthesis exclusively in the keratoconus cultures (p&lt;0.01). Platelet derived growth factor induced a reduction in SOD3 synthesis in all groups (p&lt;0.05).

    CONCLUSIONS: Here, we demonstrate that cultured keratoconus stromal cells respond with a reduced SOD3 synthesis to interleukin-1alpha, which is not the case in corresponding normal or bullous keratopathy cells. Since interleukin-1alpha is upregulated in corneal trauma and inflammation, keratoconus corneas may muster an insufficient oxidative defense under such conditions.

  • 240.
    Olofsson, Eva Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Marklund, Stefan L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Enhanced age-related cataract in copper-zinc superoxide dismutase null mice2012In: Clinical and Experimental Ophthalmology, ISSN 1442-6404, E-ISSN 1442-9071, Vol. 40, no 8, p. 813-820Article in journal (Refereed)
    Abstract [en]

    Background: As the lens is constantly exposed to light and oxygen that generate harmful reactive oxygen species, the importance of the intracellular antioxidant enzyme copper-zinc superoxide dismutase for the protection against age-related cataract development was explored.

    Methods: The development of lens opacities and the lens oxidative status were studied in different age groups of mice lacking copper-zinc superoxide dismutase and in wild-type mice. The lens opacities were quantified from lens photographs using digital image analysis. Thereafter, the lenses were homogenized and analysed regarding their contents of reduced glutathione and protein carbonyls suggestive of protein oxidation.

    Results: The 18-week-old mice of both genotypes had clear lenses. At 1 year of age, the copper-zinc superoxide dismutase null mice had developed cortical lens opacities, whereas the wild-type mice did not show equivalent changes until 2 years of age. The lens contents of glutathione decreased only in the 2-year-old wild-type mice, whereas the carbonyls increased over time without any differences between the two genotypes.

    Conclusions: This study indicates that the lack of copper-zinc superoxide dismutase may accelerate age-related lens opacity development and that intracellular superoxide-derived oxidative stress may be damaging to the lens during ageing. Participation of the anti-oxidant enzyme copper-zinc superoxide dismutase in the protection against age-related cataract was thus suggested.

  • 241.
    Parkkonen, Kimmo
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    The Extraocular Muscles in Desmin Knockout Mice.2014Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 242.
    Pedrosa Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Extraocular muscles: response to neuromusculardiseases and specific pathologies2012In: Craniofacial muscles: A new framework for understanding the effector side of craniofacial muscle control / [ed] McLoon LM, Andrade FH, New York: Springer-Verlag New York, 2012, p. 75-90Chapter in book (Other academic)
  • 243.
    Pedrosa Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Ögats intrikata muskelmaskineri2009Book (Other academic)
  • 244.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Extraocular muscles: extraocular muscle involvement in disease2010In: Encyclopedia of the eye / [ed] Joseph C. Besharse, Darlene A. Dartt, Reza Dana, Amsterdam: Elsevier, 2010, , p. 6p. 99-104Chapter in book (Other academic)
    Abstract [en]

    The extraocular muscles (EOMs) have unique functional and structural properties that truly set them apart from the other skeletal muscles in the body. Their most outstanding feature is a distinct behavior in disease. The EOMs remain unaffected in Duchenne muscular dystrophy and merosin-deficient congenital muscle dystrophy, two devastating muscle diseases causing severe handicap and precocious death. The EOMs are remarkably spared in motor neuron diseases such as amyotrophic lateral sclerosis, also a lethal neuromuscular disease. In contrast, these muscles are selectively affected in the Miller Fisher syndrome, and they are often the primary target in myasthenia gravis – two diseases affecting the neuromuscular junction.

  • 245.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Extraocular muscles: Response to neuromuscular diseases and specific pathologies2013In: Craniofacial Muscles: A New Framework for Understanding the Effector Side of Craniofacial Muscle Control / [ed] Linda K. McLoon, Francisco Andrade, New York: Springer-Verlag New York, 2013, p. 75-90Chapter in book (Refereed)
    Abstract [en]

    The response of the extraocular muscles (EOMs) to neuromuscular diseases generally differs significantly from that of the other muscles in the body. The EOMs may be early or preferentially affected in diseases such as myasthenia gravis, oculopharyngeal muscular dystrophy (OPMD), and Miller Fisher syndrome (MFS), but in contrast they remain notoriously unaffected in the muscle dystrophies originating from defects in the dystrophin–glycoprotein complex (DGC). Accumulating evidence points towards a special response of the EOMs in ALS, also distinct from that of the other striated muscles in the body. From a clinical point of view, it is important to realize that even very small disturbances of ocular motility have a great impact on visual function and quality of life. We rely upon perfect coordination of eye movements to align both foveas properly and send a single coherent image to the brain. The EOMs are the effector organ for ocular motility.

  • 246.
    Pedrosa-Domellöf, Fatima
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    McLoon, Linda K.
    Lindström, Mona
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    A sturdy connective tissue network surrounds all the extraocular muscle fibers2016In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, no 12Article in journal (Refereed)
  • 247. Potapenko, Ivan O.
    et al.
    Samolov, Branka
    Claesson Armitage, Margareta
    Byström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hjortdal, Jesper
    Donor Endothelial Cell Count Does Not Correlate With Descemet Stripping Automated Endothelial Keratoplasty Transplant Survival After 2 Years of Follow-up2017In: Cornea, ISSN 0277-3740, E-ISSN 1536-4798, Vol. 36, no 6, p. 649-654Article in journal (Refereed)
    Abstract [en]

    Purpose: To analyze the influence of low endothelial cell density (ECD) of donor cornea tissue, donor age, and sex on the transplant survival rate after Descemet stripping automated endothelial keratoplasty (DSAEK). Methods: Graft ECD, age, and sex of donors used for DSAEK (n = 1789) during 7 years (2007-2014) in 4 Scandinavian hospitals were assessed for potential association with transplant survival at 2 years of follow-up using a Cox regression model correcting for confounding factors. The data were obtained from The Swedish Cornea Transplant Registry. Results: Transplant failure occurred in 196 patients, with 69 early failures during the first 3 postoperative months, and 127 late secondary failures. Twenty-five of the late secondary failures were due to rejection. Reversible rejections occurred in 67 patients. There was no significant impact of donor age [hazard ratio (HR) 1.0, 95% confidence interval (CI), 0.99-1.02, P = 0.32] or endothelial cell count (HR 1.00, 95% CI, 0.99-1.01, P = 0.3) on the survival rate of DSAEK transplants at 2 years of follow-up. The use of donor grafts with low ECD (, 2300 cells/mm(2)) did not influence the survival rate (HR 1.3, 95% CI, 0.76-2.35, P = 0.31). Male donor sex was associated with lower 2-year graft survival (HR 1.5, 95% CI, 1.042.28, P = 0.03), but not with rejection events (P = 0.26). Conclusions: Based on data from The Swedish Cornea Transplant Registry, low donor ECD was not detrimental to graft survival, whereas donor sex seemed to influence the outcome at the end of the 2-year follow-up.

  • 248.
    Radovanovic, Dina
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Peikert, Kevin
    Lindström, Mona
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Pedrosa Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Sympathetic innervation of human muscle spindles2015In: Journal of Anatomy, ISSN 0021-8782, E-ISSN 1469-7580, Vol. 226, no 6, p. 542-548Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to investigate the presence of sympathetic innervation in human muscle spindles, using antibodies against neuropeptide Y (NPY), NPY receptors and tyrosine hydroxylase (TH). A total of 232 muscle spindles were immunohistochemically examined. NPY and NPY receptors were found on the intrafusal fibers, on the blood vessels supplying muscle spindles and on free nerve endings in the periaxial space. TH-immunoreactivity was present mainly in the spindle nerve and vessel. This is, to our knowledge, the first morphological study concerning the sympathetic innervation of the human muscle spindles. The results provide anatomical evidence for direct sympathetic innervation of the intrafusal fibers and show that sympathetic innervation is not restricted to the blood vessels supplying spindles. Knowledge about direct sympathetic innervation of the muscle spindle might expand our understanding of motor and proprioceptive dysfunction under stress conditions, for example, chronic muscle pain syndromes.

  • 249.
    Rask, Gunilla
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Effects of corneal thickness, curvature, astigmatism and direction of gaze on Goldmann applanation tonometry readings.2006In: Ophthalmic Research, ISSN 0030-3747, E-ISSN 1423-0259, Vol. 38, no 1, p. 49-55Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim of this study was to evaluate the impact of various sources of error in Goldmann applanation tonometry (GAT). OBJECTIVES: We evaluated the effect of corneal thickness, curvature, astigmatism and direction of gaze as sources of error in GAT. METHODS: Orbscan-II (Bausch & Lomb, Inc., Rochester, N.Y., USA) examinations were made on 30 healthy subjects and 9 keratoconus patients, and the intraocular pressure (IOP) was measured with GAT centrally, temporally and inferiorly, with the tonometer prism set horizontally and vertically. Orbscan-II images from 50 younger subjects and 49 older subjects were analysed retrospectively. RESULTS: IOP was lower on nasal gaze (p = 0.009) but higher on upward gaze (p < 0.001) compared with forward gaze. IOP and the corneal thickness were independently correlated (R(2) = 0.04; p = 0.003), as were the difference in astigmatic vector in the horizontal and vertical meridians and the difference in IOP measured with a horizontal and vertical prism (R(2) = 0.17; p < 0.001). No correlation between IOP and corneal curvature was found. In the keratoconus patients, IOPs were generally low, with large astigmatic differences. CONCLUSIONS: Corneal thickness, astigmatism and direction of gaze are clinically important sources of error in GAT. IOP should preferably be measured with the prism both horizontally and vertically. If only one direction is chosen, a vertical prism is less sensitive to different directions of gaze. Direction of gaze should be carefully monitored, especially in an irregular cornea.

  • 250.
    Reinis, Ainars
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Köhn, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Ocular phenotype of CORD5, an autosomal dominant retinal dystrophy associated with PITPNM3 p.Q626H mutation2013In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 91, no 3, p. 259-266Article in journal (Refereed)
    Abstract [en]

    Purpose: To describe in detail the phenotype of CORD5 in two families segregating a mutation c.1878G > C (p.Q626H) in the PITPNM3 gene. Methods: The study included 35 individuals from two different families of Swedish origin, all heterozygous for a PITPNM3 p.Q626H mutation. All participants underwent ophthalmological examination including kinetic perimetry, and in selected cases adaptometry, colour vision tests and optical coherence tomography (OCT). Electrophysiological studies were also performed. In some cases, the data were obtained from medical records. Results: The majority of patients showed subnormal visual acuity and light sensitivity from childhood. Early signs of macular degeneration were also observed. There was a progressive decrease in visual acuity leading to legal blindness in early adulthood. Electrophysiological testing showed a progressive loss of photoreceptor function restricted mainly to the cones. OCT revealed decreased macular thickness with flattened and enlarged fovea. Conclusion: Our observations of the PITPNM3 p.Q626H mutation carriers confirm that CORD5 is a disease not to mix with other retinal degenerations mapped to 17p13. The results of our clinical evaluation so far indicate that CORD5 is characterized by predominant cone dysfunction without signs of general involvement of the retinal pigment epithelium. The rod system also seems to be unaffected. In this sense, CORD5 is different from other autosomal dominant CORDs where rod involvement is present to some degree in a late phase of the disease. Some intra-and inter-familial differences regarding the severity of the clinical picture were observed.

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