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  • 101. Herbst, Kristina
    et al.
    Sander, Birgit
    Lund-Andersen, Henrik
    Broendsted, Adam Elias
    Kessel, Line
    Hansen, Michael Stormly
    Kawasaki, Aki
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Intrinsically photosensitive retinal ganglion cell function in relation to age: A pupillometric study in humans with special reference to the age-related optic properties of the lens.2012In: BMC Ophthalmology, ISSN 1471-2415, E-ISSN 1471-2415, Vol. 12, no 4Article in journal (Refereed)
    Abstract [en]

    Background: The activity of melanopsin containing intrinsically photosensitive ganglion retinal cells (ipRGC) can be assessed by a means of pupil responses to bright blue (appr.480 nm) light. Due to age related factors in the eye, particularly, structural changes of the lens, less light reaches retina. The aim of this study was to examine how age and in vivo measured lens transmission of blue light might affect pupil light responses, in particular, mediated by the ipRGC.

    Methods: Consensual pupil responses were explored in 44 healthy subjects aged between 26 and 68 years. A pupil response was recorded to a continuous 20 s light stimulus of 660 nm (red) or 470 nm (blue) both at 300 cd/m2 intensity (14.9 and 14.8 log photons/cm2/s, respectively). Additional recordings were performed using four 470 nm stimulus intensities of 3, 30, 100 and 300 cd/m2. The baseline pupil size was measured in darkness and results were adjusted for the baseline pupil and gender. The main outcome parameters were maximal and sustained pupil contraction amplitudes and the postillumination response assessed as area under the curve (AUC) over two time-windows: early (0–10 s after light termination) and late (10–30 s after light termination). Lens transmission was measured with an ocular fluorometer.

    Results: The sustained pupil contraction and the early poststimulus AUC correlated positively with age (p = 0.02, p = 0.0014, respectively) for the blue light stimulus condition only.

    The maximal pupil contraction amplitude did not correlate to age either for bright blue or red light stimulus conditions.

    Lens transmission decreased linearly with age (p < 0.0001). The pupil response was stable or increased with decreasing transmission, though only significantly for the early poststimulus AUC to 300 cd/m2 light (p = 0.02).

    Conclusions: Age did not reduce, but rather enhance pupil responses mediated by ipRGC. The age related decrease of blue light transmission led to similar results, however, the effect of age was greater on these pupil responses than that of the lens transmission. Thus there must be other age related factors such as lens scatter and/or adaptive processes influencing the ipRGC mediated pupil response enhancement observed with advancing age.

  • 102.
    Hittenkofer, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Extraocular muscles in R350P desminopathy2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 103.
    Holmgren, Gösta
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Hellman, Urban
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lundgren, Hans-Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Impact of homozygosity for an amyloidogenic transthyretin mutation on phenotype and long term outcome.2005In: Journal of Medical Genetics, ISSN 1468-6244, Vol. 42, no 12, p. 953-6Article in journal (Refereed)
  • 104. Holmstrom, Gerd
    et al.
    Hellstrom, Ann
    Jakobsson, Peter
    Lundgren, Pia
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Tornqvist, Kristina
    Wallin, Agneta
    Five years of treatment for retinopathy of prematurity in Sweden: results from SWEDROP, a national quality register2016In: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079, Vol. 100, no 12, p. 1656-1661Article in journal (Refereed)
    Abstract [en]

    Background/aims Retinopathy of prematurity (ROP) is a sight-threatening disease, requiring efficient screening and treatment. The present study aims to describe various aspects on treatment for ROP in Sweden.

    Methods Data on treatment for ROP in infants born in 2008-2012 were extracted from Swedish national register for retinopathy of prematurity, a web-based national register.

    Results During 2008-2012, 3488 infants with a gestational age (GA) at birth of <31 weeks had been screened for ROP in Sweden. Altogether, 30.3% (1057/3488) of the infants developed ROP and 5.2% (181/3488) were treated. Type 1 ROP was found in at least one eye in 83.2% (149/179) of the treated infants. One third of the eyes (32.2% right, 29.9% left eyes) were treated more than once. Laser was the only treatment in 90% of the eyes. Mean number of laser spots at first laser session was 1177 and 1386 in right and left eyes, respectively. Number of laser spots correlated negatively with GA at birth (p=0.01). There was no change in frequency of treatment or number of laser spots during the 5-year period. Anti-vascular endothelial growth factor injections were performed in 28 eyes, encircling band was used in five eyes and vitrectomies were performed in seven eyes. Twenty-six retinal surgeons performed 9.4 (range 1-37) treatment sessions in the 181 infants.

    Conclusions The present study reveals similar incidences of ROP and frequencies of treatment during the 5-year study period. Many surgeons were involved in treatment of a rather limited number of infants. The results call for national discussions on organisation of ROP treatment.

  • 105. Holmstrom, Gerd
    et al.
    Tornqvist, Kristina
    Al-Hawasi, Abbas
    Nilsson, Åsa
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Wallin, Agneta
    Hellstrom, Ann
    Increased frequency of retinopathy of prematurity over the last decade and significant regional differences2018In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 96, no 2, p. 142-148Article in journal (Refereed)
    Abstract [en]

    Purpose: Retinopathy of prematurity (ROP) causes childhood blindness globally in prematurely born infants. Although increased levels of oxygen supply lead to increased survival and reduced frequency of cerebral palsy, increased incidence of ROP is reported.

    Methods: With the help of a Swedish register for ROP, SWEDROP, national and regional incidences of ROP and frequencies of treatment were evaluated from 2008 to 2015 (n = 5734), as well as before and after targets of provided oxygen changed from 85–89% to 91–95% in 2014.

    Results: Retinopathy of prematurity (ROP) was found in 31.9% (1829/5734) of all infants with a gestational age (GA) of <31 weeks at birth and 5.7% of the infants (329/5734) had been treated for ROP. Analyses of the national data revealed an increased incidence of ROP during the 8‐year study period (p = 0.003), but there was no significant increase in the frequency of treatment. There were significant differences between the seven health regions of Sweden, regarding both incidence of ROP and frequency of treatment (p < 0.001). Comparison of regional data before and after the new oxygen targets revealed a significant increase in treated ROP in one region [OR: 2.24 (CI: 1.11–4.49), p = 0.024] and a borderline increase in one other [OR: 3.08 (CI: 0.99–9.60), p = 0.052].

    Conclusion: The Swedish national ROP register revealed an increased incidence of ROP during an 8‐year period and significant regional differences regarding the incidence of ROP and frequency of treatment.

  • 106. Holmström, G.
    et al.
    Hellström, A.
    Jakobsson, P.
    Lundgren, P.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Tornqvist, K.
    Wallin, A.
    Screening for retinopathy of prematurity can be started in postmenstrual week 31 in very premature babies!2016In: Eye (London. 1987), ISSN 0950-222X, E-ISSN 1476-5454, Vol. 30, no 11, p. 1524-1525Article in journal (Refereed)
  • 107. Holmström, Gerd E
    et al.
    Hellström, Ann
    Jakobsson, Peter G
    Lundgren, Pia
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Tornqvist, Kristina
    Wallin, Agneta
    Swedish National Register for Retinopathy of Prematurity (SWEDROP) and the Evaluation of Screening in Sweden2012In: Archives of ophthalmology (1960), ISSN 0003-9950, Vol. 130, no 11, p. 1418-1424Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate screening for retinopathy of prematurity (ROP) in Sweden and to investigate possible modifications of the present screening guidelines. Methods: Infants in Sweden with a gestational age (GA) of 31 weeks + 6 days or less are screened for ROP. Data from the Swedish national register for ROP (SWEDROP) during 2008 and 2009 were extracted and compared with a national perinatal quality register. Results: In SWEDROP, there were 1791 infants born before a GA of 32weeks from January 1, 2008, through December 31, 2009. Another 70 infants were registered in the perinatal quality register but not in SWEDROP (drop-out rate, 3.8% [70 of 1861 infants]). Seven infants died before termination of screening. In the final study cohort (1784 infants), 15.6% had mild ROP and 8.5% had severe ROP. Treatment was performed in 4.4% of the infants, none of whom had a GA at birth of more than 28 weeks. Nine infants with a GA of more than 28 weeks at birth developed stage 3 ROP, which regressed spontaneously. The total number of examinations was 9286 (964 in infants with a GA of 31 weeks), and the mean (range) number of examinations of each infant was 5.2 (1-30). Conclusions: The SWEDROP, a quality register for ROP, has a national coverage (ie, participation) of 96%. Data from 2008 to 2009 show that it seems possible to reduce the upper limit for screening in Sweden by 1 week, including only infants with a GA of 30 weeks + 6 days or less. However, such a change should be combined with a strong recommendation to neonatologists to refer also severely ill and more "mature" infants.

  • 108. Holmström, Gerd
    et al.
    Granse, Lotta
    Hellström, Ann
    Larsson, Eva
    Saric, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Sunnqvist, Birgitta
    Törnqvist, Kristina
    Wallin, Agneta
    Ten years of ROP-screening and treatment in Sweden - consideration of modified screening guidelines based on a national quality register2019In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 60, no 9Article in journal (Other academic)
    Abstract [en]

    Purpose : Description of ten years of national ROP-screening and treatment in Sweden and evaluation of the national screening program for ROP.

    Methods : The study is based on a national register for ROP, SWEDROP, with around 96% coverage. According to Swedish guidelines, all infants born at 30 weeks gestational age (GA) or less, as well as children born later but being extremely sick, should be screened for ROP during the neonatal period. Birth data are validated in the Swedish neonatal quality register, SNQ.

    Results : During the ten-year period between 2008 and 2017, 7257 infants with a GA of 30 weeks or less were registered in SWEDROP and 46.294 examinations were performed, of which 5.328 (11.5%) in infants born in gestational week 30. Mean GA was 27.6 w (range 21-30 w) and mean BW was 1116 g (range 390-2405 g). Overall, during the ten years, ROP was found in 31.8% (range 26.8-36.8%) and treatment for ROP was performed in 6% (range 4.1-7.7%) of the screened infants. Only nine infants with GA 28 w and four with GA 29 w were treated for ROP. No infant with GA 30 w was treated. Eighty-two per cent (361/441) of the treated infants had laser only and 17.7% (78/441) were treated with Anti-VEGF, alone (17 infants) or in combination with laser and/or other treatment.

    Conclusions : SWEDROP is a national register for ROP with a high national coverage. The incidence of ROP and frequency of treatment remained similar over the ten-year period. Only 13 infants born at 28 – 29 weeks GA and no child born at 30 w GA were treated for ROP. Modification of guidelines is considered, with lowering the upper limit of screening with one week, i.e. to less than 30 weeks GA. During the ten-year study period, this would have resulted in a reduction of 1680 infants (23.2%) screened for ROP and of 5.328 (11.5%) examinations.

  • 109.
    Holmström, Gerd
    et al.
    Uppsala, Sweden.
    Hellström, Ann
    Gothenburg, Swe.
    Jakobsson, Peter
    Linköping, Sweden.
    Lundgren, Pia
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Tornqvist, Kristina
    Lund, Sweden.
    Wallin, Agneta
    Stockholm, Sweden.
    Evaluation of new guidelines for ROP screening in Sweden using SWEDROP: a national quality register2015In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 93, no 3, p. 265-268Article in journal (Refereed)
    Abstract [en]

    PurposeTo investigate whether recent Swedish guidelines for Retinopathy of Prematurity (ROP) screening, that is, a gestational age (GA) at birth of <31weeks (w), are applicable in a new national cohort of prematurely born infants. MethodsSWEDROP is a national register for ROP, initiated in 2006. The present paper reports on data from the register on various aspects of screening for ROP in infants born between 2010 and 2011 and compares the results with those for a previously published cohort born between 2008 and 2009. ResultsDuring the study period, 1744 infants were screened for ROP. Mean GA was 28.4w (22-31), and mean birth weight was 1239g (382-2615). Screening started at postnatal age (PNA) 5.4w (0.4-13.3) and postmenstrual age (PMA) 33.8 w (24.9-50.1) Mean number of examinations was 5.4 per infant (1-38). Mild (stages 1-2) and severe ( stage 3) ROP was found in 15.4% and 8.7%, respectively. Treatment was performed in 4.2% (73/1744) of the infants, but in none with a GA of 30weeks or more. The first treatment was performed at a mean PNA and PMA of 12.7 w (7.7-25.4) and 37.4 w (32.1-51.4), respectively. ConclusionsRecently introduced new guidelines for ROP screening in Sweden remain applicable. Reassuringly, in infants born between 2010 and 2011, incidence of ROP, frequency and timing of treatment, frequency and timing of examinations and national coverage of ROP screening remained almost identical to those for a previous cohort from 2008 to 2009. The two SWEDROP cohorts provide a basis for discussion among Swedish ophthalmologists and neonatologists on the question of further lowering the upper screening limit with 1week.

  • 110. Jakobsson, Gunnar
    et al.
    Montan, Per
    Zetterberg, Madeleine
    Stenevi, Ulf
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lundström, Mats
    Capsule complication during cataract surgery: Retinal detachment after cataract surgery with capsule complication: Swedish Capsule Rupture Study Group report 4.2009In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 35, no 10, p. 1699-1705Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To study the incidence, characteristics, and results of retinal detachment (RD) after cataract surgery with a capsule complication.

    SETTING: Ten ophthalmic surgery departments in Sweden.

    METHODS: In this case-control study, data on cataract surgery cases with a capsule complication (study group) or with no complication (control group) in 2003 were extracted from the Swedish National Cataract Register. Patients with RD during a 3-year follow-up were identified.

    RESULTS: The study group comprised 324 patients and the control group, 331 patients. Retinal detachment occurred in 13 study group patients, for a 3-year incidence of 4.0%. In the control group, 1 patient (0.3%) had RD. Multivariate analysis showed an adjusted odds ratio (OR) of 14.8 for RD after capsule complication (95% confidence interval [CI], 1.9-114; P = .01). Subgroup analysis of the study group using a binary logistic regression model showed that male sex (OR, 8.5; 95% CI, 1.7-43.8; P = .001) and lens remnants in the vitreous (OR, 14.4; 95% CI 2.6-78.8; P = .002) were additional risk factors. Axial myopia was significantly associated with an increased risk as a single factor but not as a multiple factor. In general, the final visual outcome for RD after a capsule complication was poor; 3 eyes had a visual acuity of 0.50 or better. Eight eyes (62%) had a final visual acuity worse than 0.10 and 6 eyes, 0.02 or worse.

    CONCLUSIONS: The risk for RD after cataract surgery increased significantly when a capsule complication occurred, leading to poor final visual acuity in most cases.

  • 111.
    Janbaz, Adrihan H.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindström, Mona
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Liu, Jingxia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Intermediate Filaments in the Human Extraocular Muscles2014In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 55, no 8, p. 5151-5159Article in journal (Refereed)
    Abstract [en]

    PURPOSE.

    To investigate the distribution of the intermediate filament (IF) proteins desmin, vimentin, and nestin in human extraocular muscles (EOMs). METHODS. Healthy adult EOM samples were serially sectioned (5 and 1 mu m) and processed for immunohistochemistry, with specific antibodies (Abs) against desmin, vimentin, and nestin and different myosin heavy chains (MyHCs), including the newly characterized Ab MYH7b against MyHC slow tonic. The distribution of desmin was also studied in EOMs at 16 to 18 weeks of gestation.

    RESULTS.

    Desmin was present in the vast majority of muscle fibers. Notably, muscle fibers that contained MyHC slow tonic were either unlabeled or very weakly labeled with three different Abs against desmin. These muscle fibers had normal cytoarchitecture and intact basement membrane. In fetal muscle, desmin was also absent or weak in myotubes containing MyHC slow tonic. Nestin was detected in a large proportion of muscle fibers in the orbital layer and to some extent also in the global layer, whereas no muscle fibers contained vimentin. Desmin and nestin were enriched at neuromuscular junctions, as in limb muscle. In contrast, some myotendinous junctions lacked desmin or nestin.

    CONCLUSIONS.

    The human EOMs differed significantly from the other muscles in the body with respect to their IF composition. Desmin, hitherto regarded as a ubiquitous muscle cytoskeletal protein, was absent or only present in trace amounts in a subset of normal muscle fibers in adult and fetal EOMs. Nestin, normally downregulated early in the postnatal period, was present in a high proportion of adult muscle fibers.

  • 112.
    Janbaz, Chris C
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lundberg, Björn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Stimulation of adrenergic β-receptors enhances mydriasis in a porcine eye model2012In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 90, no 5, p. 418-421Article in journal (Refereed)
    Abstract [en]

    Purpose: To compare the mydriatic effect of intracamerally injected isoprenaline plus phenylephrine to phenylephrine alone and to epinephrine in a porcine eye model, aiming to eventually find the best combination of adrenergic substances for surgical mydriasis in humans.

    Methods: In this study, we used 89 intact eyes from newly slaughtered pigs, pretreated with 2.0 mg of intracameral acetylcholine. After waiting 60 seconds for miosis to develop, 0.15 ml 0.3% isoprenaline and 0.15 ml 3.0% phenylephrine were injected sequentially with a 90-second interval in 21 eyes. In another 22 eyes, the same substances were given in the reverse order. In 20 eyes, 0.15 ml of 0.025% epinephrine was injected, and as a negative control 0.15 ml of balanced salt solution was injected in 26 eyes. The pupils were filmed during the treatments, and the mean pupil diameters were measured every 15 seconds from the video recordings.

    Results: Phenylephrine injected after isoprenaline had a larger mydriatic effect than epinephrine (p < 0.01). Without isoprenaline pretreatment, the mydriatic effect of phenylephrine was significantly smaller than that of epinephrine (p < 0.05). Isoprenaline also exhibited a small mydriatic effect of its own.

    Conclusions: The β-receptor stimulator isoprenaline enhances the mydriatic effect of intracameral phenylephrine, indicating a role for the β-receptor in the mydriatic response. Mydriasis mediated by β-receptors may explain why nonspecific adrenergic stimulators such as epinine and epinephrine can have larger mydriatic effects than the specific α(1) -receptor stimulator phenylephrine.

  • 113.
    Johannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Ambarki, Khalid
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eklund, Anders
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Age-dependency of ocular parameters - a cross sectional study of young and old healthy subjects2015In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 56, no 7, article id Meeting Abstract: 116Article in journal (Other academic)
    Abstract [en]

    Purpose: To investigate aging effect on ocular parameters inkluding intraocular pressure (IOP) measured with different tonometry methods in healthy young (HY) and elderly (HE) subjects.

    Methods: Fifty eyes of 50 HY subjects (28 females, 22-31 years of age) and 43 eyes of 43 HE subjects (22 females, 64-79 years of age) were included. IOP was measured with four tonometry methods in a standardized order: Ocular Response Analyser (ORA), Dynamic Contour Tonometry (DCT), Applanation Resonance Tonometry (ART) and Goldmann Applanation Tonometry (GAT). Other measurements included axial length (AL), central corneal thickness (CCT), corneal curvature (CC), ocular pulse amplitude (OPA) and aqueous humor (aq).

    Results: The mean IOP (HY/HE; mmHg ± standard deviation) was 13.9 ± 2.7/16.4 ± 3.4 with ORA, 15.1 ± 2.1/16.3 ± 3.1 with DCT, 12.3 ± 2.0/13.7 ± 2.8 with GAT and 13.1 ± 2.2/12.1 ± 2.5 with ART. IOP was significantly higher (difference ± standard error) in HE compared to HY measured with ORA (+2.5 mmHg ± 0.6), GAT (+1.4 ± 0.5) and DCT (+1.2 ± 0.6). There was a trend towards lower IOP in HE when measured with ART (-1.0 ± 0.5, p=0.05). There was no difference between HE and HY in CCT, CC, AL or OPA.

    Conclusions: Tonometry methods are affected differently by age. IOP was measured higher in elderly people with ORA, DCT and GAT in this Scandinavian population. This effect was not seen in measurements with ART. Other ocular parameters did not differ between the age groups indicating that these measured parameters are not influenced by age in this population.

  • 114.
    Johannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Ambarki, Khalid
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eklund, Anders
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Age-dependency of ocular parameters: a cross sectional study of young and elderly healthy subjects2015In: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 253, no 11, p. 1979-1983Article in journal (Refereed)
    Abstract [en]

    To investigate the effect of aging on ocular parameters, including intraocular pressure (IOP), measured with different tonometry methods in healthy young (HY) and healthy elderly (HE) subjects and to study the effect of corneal parameters on tonometry methods. In this prospective, cross-sectional study, fifty eyes of 50 HY subjects (28 females, 22-31 years of age) and 43 eyes of 43 HE subjects (22 females, 64-79) were included. IOP was measured with four tonometry methods in a standardized order: ocular response analyser (ORA), dynamic contour tonometry (DCT), applanation resonance tonometry (ART) and Goldmann applanation tonometry (GAT). Other measurements included axial length (AL), central corneal thickness (CCT), corneal curvature (CC), anterior chamber volume (ACV), corneal hysteresis (CH) and corneal resistance factor (CRF). The mean IOP (HY/HE; mmHg +/- standard deviation (SD)) was 12.2 +/- 2.2/14.1 +/- 3.5 with GAT. IOP was significantly higher (difference +/- standard error) in HE compared to HY measured with an ORA (+3.1 mmHg +/- 0.6), GAT (+1.9 +/- 0.6) and DCT (+1.6 +/- 0.6). No significant difference was found in IOP measured with ART. CH and ACV were significantly lower in HE compared to HY. There was no difference between the groups in CCT, CC, AL or CRF. No tonometry method was dependant on CCT or CC. IOP measured with an ORA and via DCT and GAT was higher in HE compared to HY Swedish subjects, while IOP measured with ART did not differ between the groups. In these homogeneous groups, tonometry methods were independent of CCT and CC.

  • 115.
    Johannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Effects of topical anaesthetics and repeated tonometry on intraocular pressure2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 2, p. 111-115Article in journal (Refereed)
    Abstract [en]

    Purpose:

    To investigate the effects of repeated measurements of intraocular pressure (IOP) using Goldmann applanation tonometry (GAT) and applanation resonance tonometry (ART) to identify mechanisms contributing to the expected IOP reduction.

    Methods:

    A prospective, single-centre study with six healthy volunteers. Consecutive repeated series (six measurements/serie/method) were made alternately on both eyes for 1 hr with oxybuprocaine/fluorescein in the right eye and tetracaine in the left. The left eye was Pentacam((R)) photographed before and repeatedly for 20 min after the IOP measurements. On a separate occasion, the same volunteers received the same amount of anaesthetic drops for 1 hr but without repeated IOP measurements.

    Results:

    A significant IOP reduction occurred with both ART and GAT in the oxybuprocaine-treated eye, -4.4 mmHg and -3.8 mmHg, respectively and with ART in the tetracaine eye, -2.1 mmHg. There was a significant difference in IOP reduction between the oxybuprocaine and tetracaine eyes with ART. There was a significant drop in anterior chamber volume (ACV) immediately after the IOP measurements, -12.6 mu l that returned to pretrial level after 2 min. After 1 hr of receiving anaesthetic eye drops (without IOP measurements), the IOP decreased significantly in the oxybuprocaine eye for both ART and GAT, -3.1 and -1.7 mmHg, respectively, but not in the tetracaine eye (p = 0.72).

    Conclusion:

    The IOP reduction cannot be explained solely by aqueous humor being pressed out of the anterior chamber. While significant IOP reduction occurred with both tetracaine and oxybuprocaine after repeated mechanical applanation, the IOP reduction was significantly greater with oxybuprocaine.

  • 116.
    Johannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Koskela, Timo
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Change in intraocular pressure measurement 2 years after myopic laser-assisted subepithelial keratectomy2012In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 38, no 9, p. 1637-1642Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate intraocular pressure (IOP) measurements 24 months after laser-assisted subepithelial keratectomy (LASEK) with 3 tonometry methods-Goldmann applanation tonometry (DCT), Pascal dynamic contour tonometry (DCT), and applanation resonance tonometry (ART)-and to compare them with measurements taken preoperatively and 3 and 6 months postoperatively. SETTING: Department of Ophthalmology, Umea University, lima Sweden. DESIGN: Prospective randomized single-center. METHODS: One randomized eye per person from myopic healthy individuals who had LASEK was included. Visual acuity, central corneal thickness (CCT), corneal curvature, and IOP were measured at all time points. Six IOP measurements were performed per method, with a 5-minute lapse between methods. RESULTS: The study evaluated 38 eyes. Two years after LASEK, dynamic ART was the only method that did not measure significantly lower IOP than before LASEK (mean -0.2 mm Hg +/- 1.6 [SD]). The greatest difference was with GAT (mean -1.9 +/- 1.7 mm Hg) followed by static ART (mean -1.2 +/- 1.6 mm Hg) and then DCT (mean -0.9 +/- 1.3 mm Hg). All methods measured significantly lower IOP at 3 months and 6 months. CONCLUSIONS: Dynamic ART, which analyses IOP measurement during indentation, showed no significant difference in measured IOP after 24 months. The convex tip of the ART device and the continuous sampling of data during corneal indentation seem to be factors in why dynamic ART was less affected by corneal properties and therefore more suitable for IOP measurement in LASEK-treated eyes, although this must be confirmed in larger trials.

  • 117.
    Johannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Shulman, Shiri
    Ruckert, Rene
    Stefansson, Einar
    In Vivo Visualization of Large Choroidal Vessels Obliteration in Geographic Atrophy2017In: Retina, ISSN 0275-004X, E-ISSN 1539-2864, Vol. 37, no 2, p. E24-E24Article in journal (Refereed)
  • 118. Johansson, Björn
    et al.
    Lundström, Mats
    Montan, Per
    Stenevi, Ulf
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Capsule complication during cataract surgery: Long-term outcomes: Swedish Capsule Rupture Study Group report 32009In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 35, no 10, p. 1694-1698Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To describe the long-term outcomes after cataract extractions with a capsule rupture included in the Swedish Capsule Rupture Study.

    SETTING: Ten ophthalmic surgery departments in Sweden.

    METHODS: From the cohort of patients originally selected for inclusion in the Swedish Capsule Rupture Study, cases with a capsule complication (study group) and cases without a complication (control group) were examined approximately 3.5 years postoperatively. Visual acuity and objective and subjective parameters were registered.

    RESULTS: The study group comprised 171 patients and the control group, 198 patients. Patients with a capsule complication had a significantly worse visual outcome and a doubled risk for no improvement in preoperative visual acuity. Pupil distortion, iris damage, synechias, and subjective complaints related to the eye were significantly more common in patients with a capsule complication.

    CONCLUSION: Capsule complications decreased the probability of good postoperative visual acuity and in general yielded a worse long-term outcome after phacoemulsification surgery

  • 119.
    Johansson, Björn
    et al.
    Division of Ophthalmology, Department of Neuroscience and Locomotion, Linköping University Hospital, Linköping.
    Sundelin, Staffan
    Wikberg-Matsson, Anna
    Unsbo, Peter
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Visual and optical performance of the Akreos Adapt Advanced Optics and Tecnis Z9000 intraocular lenses: Swedish multicenter study.2007In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 33, no 9, p. 1565-72Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To compare the subjective visual and objective optical performance of 2 aspherical intraocular lenses (IOLs), the Akreos Adapt Advanced Optics (AO) (Bausch & Lomb, Inc.) and the Tecnis Z9000 (Advanced Medical Optics, Inc.). SETTING: Four university hospitals in Sweden. METHODS: This study comprised 80 patients, 20 each from 4 university hospital centers in Sweden. All patients had bilateral clear corneal phacoemulsification with implantation of an Akreos Adapt AO IOL in 1 eye and Tecnis Z9000 IOL in the other eye according to a randomization protocol. Preoperatively, 90% contrast Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity was measured and the mesopic pupil sizes were determined. Ten to 12 weeks postoperatively, 12.5% and 90% contrast ETDRS visual acuities and photopic and mesopic Functional Acuity Contrast Test chart contrast sensitivities were determined. Wavefront analysis was performed with the Zywave II aberrometer (Bausch & Lomb, Inc.), and a questionnaire on the subjective quality of vision was completed by each patient. RESULTS: The Akreos AO IOL and Tecnis Z9000 IOL produced similar high- and low-contrast visual acuities as well as photopic and mesopic contrast sensitivities. The Tecnis Z9000 IOL resulted in lower spherical aberrations of the eye (mean 0.05 +/- 0.13 microm versus 0.35 +/- 0.13 microm root mean square, 6.0 mm pupil) (P<.001); however, the Akreos AO IOL provided a larger depth of field (mean 1.22 diopter [D] +/- 0.48 [SD] versus 0.86 +/- 0.50 D, 6.0 mm pupil) (P<.001). Patient satisfaction was generally high, although 68.8% of the patients reported some type of visual disturbance postoperatively. Twenty-eight percent of patients reported better subjective visual quality in the Akreos AO eye and 14%, in the Tecnis Z9000 eye (P<.0001). Accordingly, 33% perceived more visual disturbances in the Tecnis Z9000 eye and 11%, in the Akreos AO eye (P<.0001). CONCLUSIONS: Maximum reduction of spherical aberration did not maximize subjective visual quality. The higher perceived quality of vision with the Akreos AO IOL could be because of differences in depth of field, IOL material, or IOL design.

  • 120.
    Johansson, Magdalena
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundberg, Björn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Optical coherence tomography evaluation of macular edema after phacoemulsification surgery with intracameral mydriatics.2007In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 33, no 8, p. 1436-41Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To quantify the macular edema induced by intracameral mydriatics in phacoemulsification surgery. SETTING: University hospital eye clinic, Umeå, Sweden. METHODS: In a randomized study of 22 patients, 11 patients were given 150 muL of a mixture of phenylephrine 1.5% and lidocaine 1% intracamerally for mydriasis and anesthesia. In a control group (n = 11), conventional topical mydriatics and intracameral lidocaine were given. Multiple preoperative, intraoperative, and postoperative variables were recorded. RESULTS: There were no differences in macular edema between the 2 treatments. A correlation was seen between macular edema and impaired visual acuity 1 week postoperatively. On the first postoperative day, a similar correlation was seen between corneal edema and the degree of visual improvement. CONCLUSIONS: Intracameral lidocaine and phenylephrine for mydriasis and anesthesia did not induce more significant macular edema than the standard regimen of topical mydriatics plus intracameral lidocaine. Macular edema limited visual improvement 1 week after phacoemulsification, while corneal edema appeared to have a larger effect immediately after surgery.

  • 121.
    Jonsson, Asa C
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Burstedt, Marie S I
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Tinted contact lenses in Bothnia dystrophy.2007In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 85, no 5, p. 534-539Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To determine whether tinted contact lenses can improve visual function in patients with Bothnia dystrophy (BD), a genetically defined retinal dystrophy with prolonged dark adaptation. METHODS: Twelve patients with BD were fitted with the same type of soft contact lenses tinted dark brown. Visual acuity (VA), contrast vision, near vision and visual fields were tested before and 1 month after contact lens fitting. The patients completed a visual function questionnaire. The physical properties of the contact lenses were tested using spectrophotometry. RESULTS: The patients with the lowest VA described the most obvious improvement in visual function. This group of patients preferred darker contact lenses and continued wearing their contact lenses after the study ended. The patients with the best VA preferred lighter contact lenses and a few patients in this group discontinued contact lens wear upon completion of the study. CONCLUSIONS: Visual function in BD patients was improved by dark tinted contact lenses. The optimal colour for lenses varies, depending on the season and the individual. Other patient groups with retinal dystrophies associated with prolonged dark adaptation or dysfunction of the cone system, such as cone dystrophies or achromatopsia, may also benefit from this type of contact lens.

  • 122.
    Jonsson, Frida
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Boström, Ida Maria
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Österman, Lennart
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Burstedt, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Holmberg, Monica
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    ATP-binding cassette subfamily A, member 4 intronic variants c.4773+3A > G and c.5461-10T > C cause Stargardt disease due to defective splicing2018In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 96, no 7, p. 737-743Article in journal (Refereed)
    Abstract [en]

    Purpose

    Inherited retinal dystrophies (IRDs) represent a group of progressive conditions affecting the retina. There is a great genetic heterogeneity causing IRDs, and to date, more than 260 genes are associated with IRDs. Stargardt disease, type 1 (STGD1) or macular degeneration with flecks, STGD1 represents a disease with early onset, central visual impairment, frequent appearance of yellowish flecks and mutations in the ATP‐binding cassette subfamily A, member 4 (ABCA4) gene. A large number of intronic sequence variants in ABCA4 have been considered pathogenic although their functional effect was seldom demonstrated. In this study, we aimed to reveal how intronic variants present in patients with Stargardt from the same Swedish family affect splicing.

    Methods

    The splicing of the ABCA4 gene was studied in human embryonic kidney cells, HEK293T, and in human retinal pigment epithelium cells, ARPE‐19, using a minigene system containing variants c.4773+3A>G and c.5461‐10T>C.

    Results

    We showed that both ABCA4 variants, c.4773+3A>G and c.5461‐10T>C, cause aberrant splicing of the ABCA4 minigene resulting in exon skipping. We also demonstrated that splicing of ABCA4 has different outcomes depending on transfected cell type.

    Conclusion

    Two intronic variants c.4773+3A>G and c.5461‐10T>C, both predicted to affect splicing, are indeed disease‐causing mutations due to skipping of exons 33, 34, 39 and 40 of ABCA4 gene. The experimental proof that ABCA4 mutations in STGD patients affect protein function is crucial for their inclusion to future clinical trials; therefore, functional testing of all ABCA4 intronic variants associated with Stargardt disease by minigene technology is desirable.

  • 123.
    Jonsson, Frida
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Burstedt, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Kellgren, Therese
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Non-homologous recombination between Alu and LINE-1 repeats results in a 91 kb deletion in MERTK causing severe retinitis pigmentosa2018In: Molecular Vision, ISSN 1090-0535, E-ISSN 1090-0535, Vol. 24, p. 667-678Article in journal (Refereed)
    Abstract [en]

    Purpose: Retinitis pigmentosa (RP) represents a large group of inherited retinal diseases characterized by clinical and genetic heterogeneity. Among patients with RP in northern Sweden, we identified two severely affected siblings and aimed to reveal a genetic cause underlying their disease.

    Methods: Whole exome sequencing (WES) was performed on both affected individuals. Sequence variants were filtered using a custom pipeline to find a rare or novel variant predicted to affect protein function. Genome-wide genotyping was used to identify copy number variants (CNVs) and homozygous regions with potential disease causative genes.

    Results: WES uncovered a novel heterozygous variant in the MER proto-oncogene, tyrosine kinase (MERTK) gene, c.2309A>G, p.Glu770Gly located in the tyrosine kinase domain and predicted to be likely pathogenic. The second variant, a large heterozygous deletion encompassing exons 1 to 7 of the MERTK gene, was revealed with genome-wide genotyping. The CNV analysis suggested breakpoints of the deletion, in the 5′-untranslated region and in intron 7. We identified genomic sequences at the site of the deletion as part of L1ME4b (LINE/L1) and AluSx3 that indicated a non-homologous recombination as a mechanism of the deletion evolvement.

    Conclusions: Patients with RP in this study were carriers of two novel allelic mutations in the MERTK gene, a missense variant in exon 17 and an approximate 91 kb genomic deletion. Mapping of the deletion breakpoints allowed molecular testing of a cohort of patients with RP with allele-specific PCR. These findings provide additional information about mutations in MERTK for molecular testing of unsolved recessive RP cases and highlight the necessity for analysis of large genomic deletions.

  • 124.
    Jonsson, Frida
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Burstedt, Marie S
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Norberg, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Genetic heterogeneity and clinical outcome in a Swedish family with retinal degeneration caused by mutations in CRB1 and ABCA4 genes2014In: Retinal Degenerative Diseases: Mechanisms and Experimental Therapy, Springer Berlin/Heidelberg, 2014, Vol. 801, p. 177-183Conference paper (Refereed)
    Abstract [en]

    Genetic mechanisms underlying severe retinal dystrophy in a large Swedish family presenting two distinct phenotypes, Leber congenital amaurosis and Stargardt disease were investigated. In the family, four patients with Leber congenital amaurosis were homozygous for a novel c.2557C>T (p.Q853X) mutation in the CRB1 gene, while of two cases with Stargardt disease, one was homozygous for c.5461-10T>C in the ABCA4 gene and another was a compound heterozygous for c.5461-10T>C and a novel ABCA4 mutation c.4773+3 A>G. Sequence analysis of the entire ABCA4 gene in patients with Stargardt disease revealed complex alleles with additional sequence variants.Our results provide evidence of genetic complexity causative of different clinical features present in the same family, which is an obvious challenge for ophthalmologists, molecular geneticists and genetic counsellors.

  • 125.
    Jonsson, Frida
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Burstedt, Marie S
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Norberg, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Novel mutations in CRB1 and ABCA4 genes cause Leber congenital amaurosis and Stargardt disease in a Swedish family2013In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 21, no 11, p. 1266-1271Article in journal (Refereed)
    Abstract [en]

    This study aimed to identify genetic mechanisms underlying severe retinal degeneration in one large family from northern Sweden, members of which presented with early-onset autosomal recessive retinitis pigmentosa and juvenile macular dystrophy. The clinical records of affected family members were analysed retrospectively and ophthalmological and electrophysiological examinations were performed in selected cases. Mutation screening was initially performed with microarrays, interrogating known mutations in the genes associated with recessive retinitis pigmentosa, Leber congenital amaurosis and Stargardt disease. Searching for homozygous regions with putative causative disease genes was done by high-density SNP-array genotyping, followed by segregation analysis of the family members. Two distinct phenotypes of retinal dystrophy, Leber congenital amaurosis and Stargardt disease were present in the family. In the family, four patients with Leber congenital amaurosis were homozygous for a novel c.2557C>T (p.Q853X) mutation in the CRB1 gene, while of two cases with Stargardt disease, one was homozygous for c.5461-10T>C in the ABCA4 gene and another was carrier of the same mutation and a novel ABCA4 mutation c.4773+3A>G. Sequence analysis of the entire ABCA4 gene in patients with Stargardt disease revealed complex alleles with additional sequence variants, which were evaluated by bioinformatics tools. In conclusion, presence of different genetic mechanisms resulting in variable phenotype within the family is not rare and can challenge molecular geneticists, ophthalmologists and genetic counsellors.

  • 126.
    Jonsson, Frida
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Byström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Davidson, Alice E.
    UCL Institute of Ophthalmology, London, UK.
    Backman, Ludvig J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Kellgren, Therese
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Tuft, Stephen J.
    UCL Institute of Ophthalmology, London, UK; Moorfields Eye Hospital, London, UK.
    Koskela, Timo
    Koskelas Eye Clinic, Umeå, Sweden.
    Ryden, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Hardcastle, Alison J.
    UCL Institute of Ophthalmology, London, UK.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Mutations in Collagen, Type XVII, Alpha 1 (COL17A1) Cause Epithelial Recurrent Erosion Dystrophy (ERED)2015In: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 36, no 4, p. 463-473Article in journal (Refereed)
    Abstract [en]

    Corneal dystrophies are a clinically and genetically heterogeneous group of inherited disorders that bilaterally affect corneal transparency. They are defined according to the corneal layer affected and by their genetic cause. In this study, we identified a dominantly inherited epithelial recurrent erosion dystrophy (ERED)-like disease that is common in northern Sweden. Whole-exome sequencing resulted in the identification of a novel mutation, c.2816C>T, p.T939I, in the COL17A1 gene, which encodes collagen type XVII alpha 1. The variant segregated with disease in a genealogically expanded pedigree dating back 200 years. We also investigated a unique COL17A1 synonymous variant, c.3156C>T, identified in a previously reported unrelated dominant ERED-like family linked to a locus on chromosome 10q23-q24 encompassing COL17A1. We show that this variant introduces a cryptic donor site resulting in aberrant pre-mRNA splicing and is highly likely to be pathogenic. Bi-allelic COL17A1 mutations have previously been associated with a recessive skin disorder, junctional epidermolysis bullosa, with recurrent corneal erosions being reported in some cases. Our findings implicate presumed gain-of-function COL17A1 mutations causing dominantly inherited ERED and improve understanding of the underlying pathology.

  • 127.
    Jonsson, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Pachymetric evaluation prior to laser in situ keratomileusis2005In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 31, no 4, p. 701-706Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To determine whether deviations in the localization of the cornea's thinnest point or the magnitude and localization of posterior corneal ectasia is associated with deviations in the spherical equivalent, the astigmatism, or the magnitude of an anterior corneal ectasia and whether corneas at risk for iatrogenic keratectasia can be identified without a pachymetry map of the cornea. SETTING: University hospital eye clinic. METHODS: Three hundred eight eyes of 156 healthy volunteers with various refractive errors were examined with Orbscan II and autorefractometer-keratometer. The corneal thickness was registered at the fixation point, at the geometrical center, and at the thinnest point of the cornea. Keratometry and refraction were determined for all subjects. RESULTS: The thinnest point of the cornea was predominantly located in the inferotemporal quadrant, and was significantly thinner than the fixation point (539.6 +/- 35.8 microm and 548.0 +/- 35.4 microm, respectively, P<.001). Interestingly, the larger this difference was, the longer the distance between these points. No relationship was found between the refractive or external surface measurements and the internal surface measurements. CONCLUSIONS: The absence of a clear relationship between the shape of the anterior corneal surface or the refractive error, and the shape of the posterior corneal surface, necessitates a thorough pachymetric evaluation of the cornea before a laser in situ keratomileusis procedure, with special attention to the inferotemporal area.

  • 128.
    Jonsson, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Markström, Klas
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Slit-scan tomography evaluation of the anterior chamber and corneal configurations at different ages.2006In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 84, no 1, p. 116-120Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate the aqueous humour and corneal volumes, their correlations to age, sex and refractive status, and their changes with age. METHODS: A total of 153 eyes of 153 healthy volunteers and 58 eyes of 58 patients planned for cataract surgery were examined with Orbscan II slit-scan tomography and the autorefractometer-keratometer. In 16 eyes of 16 volunteers, the same examinations were performed twice with a 4-year interval. Anterior chamber volumes were calculated with a 3-dimensional mapping method, corneal volumes were calculated, and multiple refraction and corneal/anterior chamber configuration variables were registered. RESULTS: The aqueous humour volume is inversely correlated to the age of the individual (r = - 0.22, p = 0.001), with an average decrease of 1.4 +/- 2.6 microl per year on longitudinal follow-up (p = 0.042). Specifically, the posterior part of the anterior chamber undergoes a pronounced reduction in volume with time, whereas the volume of the anterior part increases slightly with time. Increasing steepness and peripheral thinning of the cornea (p = 0.034), and a reduction in corneal volume (p = 0.037) were also seen with increasing age. Males had less steeply curved corneas and higher aqueous humour volumes than females. CONCLUSION: The anterior segment of the eye undergoes continuous alterations with age, which differ significantly between the genders. These normal differences and alterations may be of importance in the planning of refractive procedures, and in the evaluation of disease processes.

  • 129.
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Intraocular pressure: clinical aspects and new measurement methods2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Intraocular pressure (IOP) measurement is a routine procedure and a fundament in glaucoma care. Elevated IOP is the main risk factor for glaucoma, and to date, reduction of IOP is the only possible treatment.

    In a retrospective clinical material, the prevalence of open angle glaucoma was estimated on the west coast of Iceland. IOP measurement and optic nerve head examination were used to capture glaucoma suspects, within the compulsory ophthalmological examination for the prescription of eye glasses. The results were mainly in agreement with a recent prospective study in the same region. This indicated that retrospective data, under certain conditions, may contribute with useful information on the prevalence of glaucoma. However, normal tension glaucoma is underestimated if perimetry and/or fundus photography are not included in the examination.

    Three studies focused on the measurement of IOP. Goldmann applanation tonometry (GAT) is the standard method. GAT is affected by corneal properties, e.g. central corneal thickness (CCT) and corneal curvature (CC). Refractive surgery changes these properties. This has put focus on how corneal biomechanics translate into tonometric errors and stimulated the development of new methods. As a result, Pascal

    ® Dynamic Contour Tonometry (PDCT) and Icare® rebound tonometry have been introduced. A method under development by our research group is Applanation Resonance Tonometry (ART). It is based on resonance technology and estimates IOP from continuous measurement of force and contact area.

    Comparison of PDCT, Icare and GAT in a prospective study showed that the concordance to GAT was close to the limits set by the International Standard Organization (ISO) for PDCT, while Icare was outside the limits.

    To investigate if laser-assisted subepithelial keratectomy (LASEK) affects tonometry, a study was performed where measurements with GAT, PDCT and ART were obtained before, three and six months after LASEK. The hypothesis was that PDCT and ART would be less affected by LASEK than GAT. The results showed a statistically significant reduction of measured IOP three and six months after LASEK for all tonometry methods. Change in visual acuity and IOP between three and six months suggested a prolonged postoperative process.

    A servo-controlled prototype (ART

    servo) was developed. A study was undertaken to assess the agreement of ARTservo and a further developed v

    manual prototype (ART

    manual) with GAT. The study design was in accordance with the requirements of the ISO standard for tonometers. ARTmanual fulfilled the precision requirements of the ISO standard. ARTservo did not meet all the requirements of the standard at the highest pressure levels.

    Four tonometry methods, GAT, PDCT, Icare and ART, were investigated. None of them was independent of both CCT and CC. The inconsistencies in the results emphasize the importance of study design. A meta-analysis comprising healthy eyes (IOP ≤ 21 mmHg) in the three papers, revealed age as an important confounder.

    In summary, glaucoma prevalence in Iceland was investigated and the results indicated that a retrospective approach can contribute with meaningful information. ART and PDCT had a similar agreement to GAT. ART

    manual fulfilled the precision requirements set by the ISO-standard, ARTservo and PDCT were close, while Icare was distinctly outside the limits. All tonometry methods were affected by LASEK and no method was completely independent of corneal properties.

  • 130.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Abouzeid, Hana
    Somner, John Edward Almond
    Association between rate of binocular visual field change and vision-related quality of life: novel finding or spurious association?2014In: JAMA ophthalmology, ISSN 2168-6165, E-ISSN 2168-6173, Vol. 132, no 6, p. 784-785Article in journal (Refereed)
  • 131.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Intracranial and Intraocular Pressure at the Lamina Cribrosa: Gradient Effects2018In: Current Neurology and Neuroscience Reports, ISSN 1528-4042, E-ISSN 1534-6293, Vol. 18, no 5, article id 25Article, review/survey (Refereed)
    Abstract [en]

    Purpose of Review A pressure difference between the intraocular and intracranial compartments at the site of the lamina cribrosa has been hypothesized to have a pathophysiological role in several optic nerve head diseases. This paper reviews the current literature on the translamina cribrosa pressure difference (TLCPD), the associated pressure gradient, and its potential pathophysiological role, as well as the methodology to assess TLCPD. Recent Findings For normal-tension glaucoma (NTG), initial studies indicated low intracranial pressure (ICP) while recent findings indicate that a reduced ICP is not mandatory. Summary Data from studies on the elevated TLCPD as a pathophysiological factor of NTG are equivocal. From the identification of potential postural effects on the cerebrospinal fluid (CSF) communication between the intracranial and retrolaminar space, we hypothesize that the missing link could be a dysfunction of an occlusion mechanism of the optic nerve sheath around the optic nerve. In upright posture, this could cause an elevated TLCPD even with normal ICP and we suggest that this should be investigated as a pathophysiological component in NTG patients.

  • 132.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Gudmundsdóttir, Gudrún J
    Rejykjavik, Island.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Can the prevalence of open-angle glaucoma be estimated from a retrospective clinical material? A study on the west coast of Iceland.2005In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 83, no 5, p. 549-553Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To explore the possibility of estimating the prevalence of open-angle glaucoma (OAG) on the west coast of Iceland using a clinical retrospective material, and to compare that estimate with the results from a recent prospective Icelandic study.

    METHODS: The compulsory ophthalmological examination for the prescription of eye glasses in combination with information obtained from Statistics Iceland were used to establish the prevalence of glaucoma in Akranes and to estimate the minimum prevalence for the greater west coast area. A recent prospective study from Iceland was used as reference.

    RESULTS: In all, 79% of 1443 Akranes inhabitants aged 50 years or more had visited the eye clinic at least once between 1996 and 2001. The prevalence of OAG was 4.8% (95% CI 3.6-6.1). The minimum prevalence for the west coast was 3.8% (95% CI 3.2-4.4). The prevalence increased with age (p < 0.001). The overall prevalence was similar to that of recently published prospective data but the prevalence of normal tension glaucoma (NTG) was lower.

    CONCLUSION: The results from the two studies are similar in many respects, which indicates that retrospective data may supply meaningful information on glaucoma prevalence. Important sources of error are the selection and attendance of patients, screening methods and diagnostic criteria. If routine examination does not include fundus photography and/or perimetry, the prevalence of NTG will be underestimated.

  • 133.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Koskela, Timo
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Change in intraocular pressure measurement after myopic LASEK: a study evaluating Goldmann, Pascal and applanation resonance tonometry2012In: Journal of glaucoma, ISSN 1057-0829, E-ISSN 1536-481X, Vol. 21, no 4, p. 255-259Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To prospectively evaluate 3 tonometry methods-the gold standard, Goldmann applanation tonometry, a new method, Pascal dynamic contour tonometry (PDCT), and a method under development, applanation resonance tonometry (ART)-with respect to intraocular pressure (IOP) measurements before, 3 and 6 months after laser-assisted subepithelial keratectomy (LASEK).

    MATERIALS AND METHODS: One randomly assigned eye of each of 53 healthy individuals, who underwent LASEK surgery for myopia was studied. Visual acuity, central corneal thickness, corneal curvature, and IOP were measured at each visit. Six IOP measurements/methods with 5 minutes pause between methods were performed.

    RESULTS: All tonometry methods measured a significantly lower IOP after LASEK correction by a mean of -3.1 diopters. The IOP reduction was largest after 6 months for Goldmann applanation tonometry (-1.7±1.8 mm Hg) followed by ARTstat (-1.2±1.5 mm Hg), PDCT (-1.1±1.6 mm Hg), and ARTdyn (-1.0±1.5 mm Hg). The reduction of IOP did not differ significantly between different methods (P=0.11). There was a significant further reduction of measured IOP for PDCT between 3 and 6 months (-0.5±1.0 mm Hg). Uncorrected visual acuity improved significantly between 3 and 6 months postoperatively from 1.32±0.28 to 1.43±0.27.

    CONCLUSIONS: All tonometry methods measured a significant, but low, reduction of IOP 3 and 6 months after LASEK. Further change in visual acuity and IOP measurements between 3 and 6 months suggest a still ongoing postoperative process.

  • 134.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Introduction and clinical evaluation of servo-controlled applanation resonance tonometry2012In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 90, no 7, p. 677-682Article in journal (Refereed)
    Abstract [en]

    Purpose:  In recent years, Applanation Resonance Tonometry (ART) has been suggested for intraocular pressure (IOP) measurements. The manual version of ART (ARTmanual) has been further developed, and to improve usability, an automatic servo-controlled prototype (ARTservo) has been proposed. The aim of this study was to assess the limits of agreement (LoA) of ARTmanual and ARTservo as compared with the reference method, Goldmann Applanation Tonometry (GAT).

    Methods:  This was a prospective single-centre study on 152 eyes from 77 subjects. It was designed according to International Standard Organization’s (ISO) requirements for tonometers (ISO 2001). Intraocular pressure was measured six times/method in a standardized order. The ART technique has two available analysis procedures: a dynamic one that measures IOP during the indentation phase and a static one that causes a Goldmann-like measurement during two seconds of full applanation. The 95% LoA was defined as ±1.96 × standard deviation of difference against GAT.

    Results:  Mean IOP for GAT was 19.1 mmHg (range: 10–37 mmHg). The 95% LoA of ARTmanual was ±4.5 mmHg for both dynamic and static analyses. The 95% LoA of ARTservo was ±5.7 mmHg for dynamic and ±4.9 mmHg for static analyses.

    Conclusions:  This study confirms that the ART methodology is feasible. The further developed ARTmanual fulfilled the ISO standard with both the dynamic and the static analysis techniques. ARTservo with static analysis was close to fulfilling the standard but failed to do so in the highest IOP range. ARTservo has the potential to greatly improve usability if further development is completed.

  • 135.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Pascal, ICare and Goldmann applanation tonometry: a comparative study2008In: Acta ophthalmologica, ISSN 1755-3768, Vol. 86, no 6, p. 614-621Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To compare intraocular pressure (IOP) measurements by Pascal, ICare and Goldmann applanation tonometry (GAT), to evaluate the effects of central corneal thickness (CCT) and curvature on IOP measurement and to estimate the intra-observer variability.

    METHODS: A prospective, single-centre study of 150 eyes with a wide range of pressures. Six masked IOP measurements/method; corneal thickness and curvature were studied for each eye. GAT was the reference.

    RESULTS: IOPPascal and IOPICare correlated with IOPGAT (r = 0.91, 0.89). Mean ICare measurement exceeded GAT by 2 mmHg. Pascal measured higher than GAT at low IOPs and lower at high IOPs. For every 10 mmHg increase in IOP above 31 mmHg, Pascal measured 2 mmHg lower than GAT and vice versa. CCT was correlated significantly with IOPGAT (r = 0.23) and IOPICare (r = 0.43) but not with IOPPascal (P = 0.12). CCT was correlated with age. In a subgroup (>50 years), ICare and the difference between IOPGAT and IOPPascal were affected significantly by the CCT, whereas IOPGAT and IOPPascal were not. Corneal curvature was correlated significantly with IOPGAT (r = -0.27) and IOPPascal (r = -0.26) but not with IOPICare (P = 0.60). Intra-observer variability within each set of six measurements was approximately 2 mmHg, irrespective of method.

    CONCLUSION: This study showed a reasonable overall correlation and concordance between the IOP obtained with the three instruments. None of the methods were completely independent of the biomechanical properties of the cornea. ICare showed a significant dependency upon CCT, whereas GAT and Pascal showed a significant dependency on corneal curvature. All methods showed intra-observer variability, which leaves room for further improvement of methods.

  • 136.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Koskela, Timo
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Change in intraocular pressure measurement after myopic LASEK: a study evaluating Goldmann, Pascal and applanation resonance tonometryArticle in journal (Refereed)
  • 137.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Can we trust intraocular pressure measurements in eyes with intracameral air?2014In: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 252, no 10, p. 1607-1610Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate the effect of intracameral air on intraocular pressure (IOP) measurements using Goldmann applanation tonometry (GAT) and applanation resonance tonometry (ART) in an in-vitro porcine eye model.

    METHODS: IOP was measured on thirteen freshly enucleated eyes at three reference pressures: 20, 30, and 40 mmHg. Six measurements/method were performed in a standardized order with GAT and ART respectively. Air was injected intracamerally in the same manner as during Descemet's stripping endothelial keratoplasty (DSEK) and Descemet's membrane endothelial keratoplasty (DMEK), and the measurements were repeated.

    RESULTS: Measured IOP increased significantly for both tonometry methods after air injection: 0.7 ± 2.1 mmHg for GAT and 10.6 ± 4.9 mmHg for ART. This difference was significant at each reference pressure for ART but not for GAT.

    CONCLUSIONS: Although slightly affected, this study suggests that we can trust GAT IOP-measurements in eyes with intracameral air, such as after DSEK/DMEK operations. Ultrasound-based methods such as ART should not be used.

  • 138.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Department of Ophthalmology, National University Hospital, University of Iceland, Reykjavik, Iceland.
    Moya-Ortega, Maria D
    Ásgrímsdóttir, Gudrun Marta
    Agnarsson, Bjarni A
    Lund, Sigrún H
    Loftsson, Thorsteinn
    Stefánsson, Einar
    Dorzolamide cyclodextrin nanoparticle suspension eye drops and trusopt in rabbit2014In: Journal of Ocular Pharmacology and Therapeutics, ISSN 1080-7683, E-ISSN 1557-7732, Vol. 30, no 6, p. 464-467Article in journal (Refereed)
    Abstract [en]

    Abstract Purpose: Dorzolamide nanoparticle γ-cyclodextrin eye drops may prolong the effect of dorzolamide on intraocular pressure. We test whether the nanoparticle drops have an irritating or toxic effect on the eye in an in vivo rabbit model. Methods: Eighteen pigmented rabbits were divided into 4 groups receiving dorzolamide nanoparticle γ-cyclodextrin eye drops×1/day or×2/day, Trusopt(®) (dorzolamide HCl)×3/day, and untreated controls that received no drops. The rabbits received treatment for 1 month. After sacrifice, 33 eyes and 25 Harderian glands were evaluated for histopathology in a masked way. Results: Mild inflammation was seen in 19/31 eyes and 13/23 Harderian glands. The difference in inflammation (n=eyes/n=glands)between the γ-cyclodextrin nanoparticle eye drops×1/day (n=5/5),×2/day (n=5/3), Trusopt (n=7/4), or untreated control (n=2/0) groups was nonsignificant in both eyes and glands (P=0.87 and P=0.92) Acute inflammation was seen in 1 Harderian gland that received γ-cyclodextrin nanoparticle eye drops×2/day. The difference in conjunctival injection between the groups was nonsignificant (P=0.30). Conclusions: Dorzolamide γ-cyclodextrin nanoparticle eye drops are no more locally toxic or irritating to the eye than Trusopt.

  • 139.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Department of Ophthalmology, University of Iceland, National University Hospital, IS 101 Reykjavík, Iceland.
    Moya-Ortega, Maria D
    Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland and Oculis Ehf., Reykjavik, Iceland.
    Ásgrímsdóttir, Gudrún Marta
    Oculis Ehf., Reykjavik, Iceland .
    Lund, Sigrún H
    Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
    Thorsteinsdóttir, Margrét
    Loftsson, Thorsteinn
    Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland.
    Stefánsson, Einar
    Department of Ophthalmology, University of Iceland, National University Hospital, IS 101 Reykjavík, Iceland .
    Kinetics of γ-cyclodextrin nanoparticle suspension eye drops in tear fluid2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 6, p. 550-556Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We have developed nanoparticle γ-cyclodextrin dexamethasone (DexNP) and dorzolamide (DorzNP) eye drops that provide sustained high drug concentrations on the eye surface. To test these characteristics, we measured dexamethasone and dorzolamide levels in tear fluid in humans following eye drop administration.

    METHODS: Concentration of dexamethasone was measured by mass spectrometry. One drop of DexNP was instilled into one eye. Tear fluid was sampled with microcapillary pipettes at seven time-points after drop instillation. Control eyes received Maxidex(®) (dexamethasone). The same procedure was performed for dorzolamide with DorzNP and Trusopt(®) .

    RESULTS: Six subjects were included in each group. The peak concentration (μg/ml ± standard deviation) of dexamethasone for DexNP eye drops (636.6 ± 399.1) was up to 19-fold higher than with Maxidex(®) (39.3 ± 18.9) (p < 0.001). At 4 hr, DexNP was still 10 times higher than Maxidex(®) . In addition, DexNP resulted in about 30-fold higher concentration of dissolved dexamethasone in the tear fluid of extended time period allowing more drug to partition into the eye tissue. The overall concentration of dorzolamide was about 50% higher for DorzNP (59.5 ± 76.9) than Trusopt(®) (40.0 ± 76.7) (p < 0.05).

    CONCLUSION: The results indicate high and extended concentration of dissolved dexamethasone with DexNP, which can explain the greater and longer lasting effect of dexamethasone in the cyclodextrin nanoparticle drug delivery platform. Dexamethasone seems to fit the cyclodextrin nanoparticle suspension drug delivery platform with longer duration and higher concentrations in tear fluid than available commercial drops, while dorzolamide is less suitable.

  • 140.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Department of ophthalmology, Faculty of medicine, University of Iceland, Reykjavik, Iceland.
    Stefánsson, Einar
    Loftsson, Thorsteinn
    Microspheres and Nanotechnology for Drug Delivery2016In: Developments in ophthalmology, ISSN 1662-2790, Vol. 55, p. 93-103Article in journal (Refereed)
    Abstract [en]

    Ocular drug delivery to the posterior segment of the eye can be accomplished by invasive drug injections into different tissues of the eye and noninvasive topical treatment. Invasive treatment involves the risks of surgical trauma and infection, and conventional topical treatments are ineffective in delivering drugs to the posterior segment of the eye. In recent years, nanotechnology has become an ever-increasing part of ocular drug delivery. In the following, we briefly review microspheres and nanotechnology for drug delivery to the eye, including different forms of nanotechnology such as nanoparticles, microparticles, liposomes, microemulsions and micromachines. The permeation barriers and anatomical considerations linked to ocular drug delivery are discussed and a theoretical overview on drug delivery through biological membranes is given. Finally, in vitro, in vivo and human studies of x03B3;-cyclodextrin nanoparticle eyedrop suspensions are discussed as an example of nanotechnology used for drug delivery to the eye.

  • 141. Kardon, Randy
    et al.
    Anderson, Susan C
    Damarjian, Tina G
    Grace, Elizabeth M
    Stone, Edwin
    Kawasaki, Aki
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Chromatic pupil responses: preferential activation of the melanopsin-mediated versus outer photoreceptor-mediated pupil light reflex2009In: Ophthalmology (Rochester, Minn.), ISSN 0161-6420, E-ISSN 1549-4713, Vol. 116, no 8, p. 1564-1573Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To weight the rod-, cone-, and melanopsin-mediated activation of the retinal ganglion cells, which drive the pupil light reflex by varying the light stimulus wavelength, intensity, and duration.

    DESIGN: Experimental study.

    PARTICIPANTS: Forty-three subjects with normal eyes and 3 patients with neuroretinal visual loss.

    METHODS: A novel stimulus paradigm was developed using either a long wavelength (red) or short wavelength (blue) light given as a continuous Ganzfeld stimulus with stepwise increases over a 2 log-unit range. The pupillary movement before, during, and after the light stimulus was recorded in real time with an infrared illuminated video camera.

    MAIN OUTCOME MEASURES: The percent pupil contraction of the transient and sustained pupil response to a low- (1 cd/m(2)), medium- (10 cd/m(2)), and high-intensity (100 cd/m(2)) red- and blue-light stimulus was calculated for 1 eye of each subject. From the 43 normal eyes, median and 25th, 75th, 5th, and 95th percentile values were obtained for each stimulus condition.

    RESULTS: In normal eyes at lower intensities, blue light evoked much greater pupil responses compared with red light when matched for photopic luminance. The transient pupil contraction was generally greater than the sustained contraction, and this disparity was greatest at the lowest light intensity and least apparent with bright (100 cd/m(2)) blue light. A patient with primarily rod dysfunction (nonrecordable scotopic electroretinogram) showed significantly reduced pupil responses to blue light at lower intensities. A patient with achromatopsia and an almost normal visual field showed selective reduction of the pupil response to red-light stimulation. A patient with ganglion cell dysfunction owing to anterior ischemic optic neuropathy demonstrated global loss of pupil responses to red and blue light in the affected eye.

    CONCLUSIONS: Pupil responses that differ as a function of light intensity and wavelength support the hypothesis that selected stimulus conditions can produce pupil responses that reflect phototransduction primarily mediated by rods, cones, or melanopsin. Use of chromatic pupil responses may be a novel way to diagnose and monitor diseases affecting either the outer or inner retina.

  • 142. Kardon, Randy
    et al.
    Anderson, Susan C
    Damarjian, Tina G
    Grace, Elizabeth M
    Stone, Edwin
    Kawasaki, Aki
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Chromatic pupillometry in patients with retinitis pigmentosa2011In: Ophthalmology (Rochester, Minn.), ISSN 0161-6420, E-ISSN 1549-4713, Vol. 118, no 2, p. 376-381Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the chromatic pupillary response as a means of assessing outer and inner retinal function in patients with retinitis pigmentosa (RP).

    DESIGN: Evaluation of diagnostic technology.

    PARTICIPANTS: Thirty-two patients with RP and visual loss and 43 normal subjects.

    METHODS: Patients were tested with a chromatic pupillometer using red and blue lights (1, 10, and 100 cd/m(2)), and their pupil responses were compared with those from 43 normal subjects (reported previously). Visual field and electroretinography (ERG) results were examined and compared with the pupil responses.

    MAIN OUTCOME MEASURES: The percent pupil contraction of the transient response to a low-intensity (1 cd/m(2)) blue light and high-intensity (100 cd/m(2)) red light and the sustained response to a high-intensity blue light was calculated for 1 eye of each subject.

    RESULTS: The pupil responses to red and blue light at all intensities were recordable in all patients except 1, whose pupil responded only to bright blue light. There was a significant difference of the pupil response between patients with RP and normal subjects in testing conditions that emphasized rod (1 cd/m(2) blue light) or cone (100 cd/m(2) red light) contribution (P<0.001). Patients with a non-recordable scotopic ERG showed significantly reduced pupil responses (P<0.001) to low-intensity blue light (1 cd/m(2)). Patients with a non-recordable or abnormal photopic ERG showed significantly reduced pupil responses (P<0.05) to high-intensity red light (100 cd/m(2)). Patients with a nonrecordable ERG had the most visual field loss and reduced pupil responses. Unexpectedly, patients with RP showed a slower re-dilation of the pupil after termination of bright blue light compared with red light, a pattern not observed in normal subjects.

    CONCLUSIONS: Pupil responses to red and blue light stimuli weighted to favor cone or rod input are significantly reduced in patients with RP but are still recordable in patients having a non-recordable ERG. In addition, outer photoreceptor disease appears to unmask a post-illumination pupillary constriction to bright blue light, most likely mediated by intrinsic activation of melanopsin ganglion cells. Chromatic pupillometry provides a novel, noninvasive method for following retinal functional status, particularly in patients with severe RP and non-recordable ERG.

  • 143. Kawaji, Takahiro
    et al.
    Ando, Yukio
    Ando, Eiko
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Tanihara, Hidenobu
    Transthyretin-related vitreous amyloidosis in different endemic areas.2010In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 17, no 3-4, p. 105-108Article in journal (Refereed)
    Abstract [en]

    Background: to investigate the vitreous opacity in patients with familial amyloidotic polyneuropathy (FAP) in two major endemic areas, Japan and Sweden. Methods: we obtained clinical data for 90 patients with vitreous opacity that was associated with FAP amyloidogenic transthyretin (ATTR) Val30Met; 18 Japanese patients and 72 Swedish patients. We reviewed medical records at Kumamoto University Hospital in Japan and Umeå University Hospital in Sweden. We evaluated the characteristics of the patients, systemic and ocular histories, clinical findings and treatment. RESULTS: swedish patients were significantly older at the onset of vitreous opacity (mean age 67.8 years) than were Japanese patients (47.6 years). A similar age difference was found for the onset of polyneuropathy. In addition, Swedish patients without polyneuropathy were significantly older (74.1 years) at the onset of vitreous opacity than those with polyneuropathy (64.6 years). A significant difference in the occurrence of vitreous opacity as the only manifestation of FAP was seen for Swedish patients (35%) compared with Japanese patients (6%). CONCLUSIONS: swedish FAP ATTR Val30Met patients appeared to develop vitreous opacity later and more frequently compared with Japanese patients.

  • 144.
    Kawasaki, Aki
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Selective wavelength pupillometry to evaluate outer and inner retinal photoreception2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Purpose

    Intrinsically photosensitive retinal ganglion cells (ipRGCs) express a unique photopigment called melanopsin. Capable of direct phototransduction, the ipRGCs are also influenced by rods and cones via synaptic inputs.  Thus, the photoinput that mediates the pupil light reflex derives from both outer (rods and cones) and inner (melanopsin-mediated) retinal photoreception. This thesis has aimed to develop a pupillometric test that provides quantitative information about the functional status of outer and inner retinal photoreception in healthy eyes and in eyes with retinal degeneration. In addition to regulating the pupil light reflex, the ipRGCs signal light information for the circadian rhythm, thus, these two non-visual physiologic responses to inner retinal photoreception were examined simultaneously.

    Methods

    Pupil responses to a long and short wavelength light over a range of intensities (under conditions of light, mesopic and dark adaptation) were recorded using a customized infrared computerized pupillometer. Results were compared for two groups: patients with retinitis pigmentosa and controls. The response function threshold intensity and a half-max intensity was determined from the rod-weighted and cone-weighted pupil responses and correlated to extent of visual loss. The pupil response to light offset was assessed as a measure of direct melanopsin activation. Lastly, pupil responses to red and blue light at equal photo flux were recorded hourly during a 24-hour period and correlated to salivary melatonin concentrations in healthy subjects.

    Results

    In normal eyes, the blue light evoked greater pupil responses compared to equiluminant red light. With increasing intensity, pupil contraction became more sustained which was most apparent with the brightest blue light. In patients with retinitis pigmentosa, the pupil responses mediated predominantly by rod and cone activation were significantly reduced compared to controls, (p<0.001) and the relative decrease in their contribution resulted in a greater influence of melanopsin on the post-stimulus response. Even at endstage retinal degeneration, pupil responses that derived predominantly from residual cone activity were detectable. The threshold intensity of the rod-mediated, but not cone-mediated, pupil response was also significantly reduced (p=0.006) in patients and the half-maximal intensity of rods correlated with severity of visual loss (r2=0.7 and p=0.02). In healthy controls, the melanopsin-mediated pupil response demonstrated a circadian modulation whereas the cone-mediated pupil response did not.

    Conclusion

    Early and progressive loss of rod function in mild-moderate stages of retinitis pigmentosa is detectable and quantifiable as a progressive loss of pupillary sensitivity to extremely dim blue lights obtained under conditions of dark adaptation. In advanced stages of retinal degeneration, chromatic pupillometry is more sensitive than standard electroretinography for detecting residual levels of rod and especially cone activity. In addition, selective wavelength pupillometry can assess non-visual light-dependent functions. The timing of the post-stimulus pupil response to blue light is in phase with melatonin secretion, suggesting a circadian regulation of this pupil parameter.

  • 145.
    Kawasaki, Aki
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Crippa, Sylvain V
    Kardon, Randy
    Leon, Lorette
    Hamel, Christian
    Characterization of pupil responses to blue and red light stimuli in autosomal dominant retinitis pigmentosa due to NR2E3 mutation2012In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 53, no 9, p. 5562-5569Article in journal (Refereed)
    Abstract [en]

    Purpose. We characterized the pupil responses that reflect rod, cone, and melanopsin function in a genetically homogeneous cohort of patients with autosomal dominant retinitis pigmentosa (adRP).

    Methods. Nine patients with Gly56Arg mutation of the NR2E3 gene and 12 control subjects were studied. Pupil and subjective visual responses to red and blue light flashes over a 7 log-unit range of intensities were recorded under dark and light adaptation. The pupil responses were plotted against stimulus intensity to obtain red-light and blue-light response curves.

    Results. In the dark-adapted blue-light stimulus condition, patients showed significantly higher threshold intensities for visual perception and for a pupil response compared to controls (P = 0.02 and P = 0.006, respectively). The rod-dependent, blue-light pupil responses decreased with disease progression. In contrast, the cone-dependent pupil responses (light-adapted red-light stimulus condition) did not differ between patients and controls. The difference in the retinal sensitivity to blue and red stimuli was the most sensitive parameter to detect photoreceptor dysfunction. Unexpectedly, the melanopsin-mediated pupil response was decreased in patients (P = 0.02).

    Conclusions. Pupil responses of patients with NR2E3-associated adRP demonstrated reduced retinal sensitivity to dim blue light under dark adaptation, presumably reflecting decreased rod function. Rod-dependent pupil responses were quantifiable in all patients, including those with non-recordable scotopic electroretinogram, and correlated with the extent of clinical disease. Thus, the chromatic pupil light reflex can be used to monitor photoreceptor degeneration over a larger range of disease progression compared to standard electrophysiology.

  • 146.
    Kawasaki, Aki
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Munier, Francis L.
    Leon, Lorette
    Kardon, Randy H.
    Pupillometric Quantification of Residual Rod and Cone Activity in Leber Congenital Amaurosis2012In: Archives of ophthalmology (1960), ISSN 0003-9950, Vol. 130, no 6, p. 798-800Article in journal (Refereed)
  • 147.
    Kjellgren, Daniel
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Human extraocular muscles: molecular diversity of a unique muscle allotype2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Introduction: The extraocular muscles (EOMs) are considered a separate class of skeletal muscle, allotype. Myosin is the major contractile protein in muscle. The myosin heavy chain (MyHC) isoforms are the best molecular markers of functional heterogeneity of muscle fibers. The relaxation rate, reflects the rate at which Ca2+ is transported back into the sarcoplasmic reticulum (SR) mostly by SR Ca2+ATPase (SERCA). Myosin binding protein C (MyBP-C), plays a physiological role in regulating contraction. The laminins (Ln) are the major non-collagenous components of the basement membrane (BM) surrounding muscle fibers and are important for muscle fiber integrity.

    Methods: Adult human EOMs were studied with SDS-PAGE, immunoblots and immunocytochemistry, the latter with antibodies against six MyHC, 2 SERCA, 2 MyBP-C and 8 laminin chain isoforms. The capillary density was also determined.

    Results: Most fibers contained a mixture of MyHC isoforms. Three major groups of fibers could be distinguished. Fast fibers that stained with anti-MyHCIIa, slow fibers that stained with anti-MyHCI and MyHCeompos/MyHCIIaneg-fibers that stained with neither of these antibodies but with anti-MyHCI+IIa+eom and anti-MyHCeom. A majority of the fibers contained both SERCA1 and 2 whereas 1% were unstained with both antibodies. Biochemically SERCA2 was more abundant than SERCA1. MyBP-Cfast was not present in the EOMs and MyBP-Cslow was only detected immunocytochemically. The extrasynaptical BM of the EOM muscle fibers contained Lna2, b1, b2, g1, a4 and a5 chains. The capillary density in the EOMs was very high (1050 +/-190 capillaries/mm2) and significantly (p<0.05) higher in the orbital than in the global layer.

    Conclusions: The co-existence of complex mixtures of several crucial protein isoforms provide the human EOMs with a unique molecular portfolio that a) allows a highly specific fine-tuning regime of contraction and relaxation, and b) imparts structural properties that are likely to contribute to protection against certain neuromuscular diseases.

  • 148.
    Kjellgren, Daniel
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Ryan, Michelle
    Ohlendieck, Kay
    Thornell, Lars-Eric
    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.
    Sarco(endo)plasmic reticulum ca2+ATPases (SERCA1 and 2) in human extraocular muscles2003In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 44, no 12, p. 5057-5062Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate the composition of the fibers in human extraocular muscles (EOMs) with respect to the sarco(endo)plasmic reticulum Ca(2+)ATPases (SERCA)-1 and -2 and to investigate possible correlations between SERCA and myosin heavy chain (MyHC) composition. METHODS: EOM samples were processed for immunocytochemistry with monoclonal antibodies specific against SERCA1 (fast isoform), SERCA2 (slow isoform), or different MyHCs. A total of 1571 fibers were analyzed. Microsomal EOM fractions were analyzed with SDS-PAGE and immunoblots. RESULTS: The fast fibers, containing MyHCIIa, accounted for 79% of the fibers in the orbital layer (OL) and 74% in the global layer (GL). More than 99% of these fibers contained SERCA1, and 86% of them coexpressed SERCA1 and -2. Almost all slow fibers stained with SERCA2; 54% of those in the GL and all in the OL coexpressed SERCA1 and -2. Fifteen percent of the fibers in the GL and less than 1% in the OL were MyHCeom(pos)/MyHCIIa(neg) fibers. All these contained SERCA1 and in the OL also stained strongly with anti-SERCA2. Biochemically SERCA2 was more abundant than SERCA1. CONCLUSIONS: The human EOMs had a very complex pattern of expression of the major protein regulating fiber relaxation rate. The coexistence of SERCA1 and -2, together with complex mixtures of MyHCs in most of the fibers provide the human EOMs with a unique molecular portfolio that allows a highly specific fine-tuning regimen of contraction and relaxation.

  • 149.
    Kjellgren, Daniel
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Larsson, Lars
    Uppsala University.
    Fürst, Dieter
    University of Bonn.
    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.
    Uncoordinated expression of myosin heavy chains and myosin-binding protein C isoforms in human extraocular muscles2006In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 47, no 10, p. 4188-4193Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To examine the distribution of myosin-binding protein C (MyBP-C) in human extraocular muscles (EOMs) and to correlate the myosin heavy chain (MyHC) and the MyBP-C composition of the fibers. METHODS: Samples from 17 EOMs, 3 levator palpebrae (LP), and 6 limb muscles were analyzed with SDS-PAGE and immunoblot or processed for immunocytochemistry with monoclonal antibodies (mAbs) against MyBP-C-fast, MyBP-C-slow, MyHCIIa, MyHCI, MyHCsto, MyHCalpha-cardiac, and MyHCemb. RESULTS: In the limb muscle samples, fast fibers were labeled with anti-MyBP-C-fast and anti-MyBP-C-slow, whereas the slow fibers were immunostained with anti-MyBP-C-slow only, in accordance with previous studies. In 11 EOM samples MyBP-C-fast was not detected, and weak staining with anti-MyBP-C-fast was seen only in a few fibers in the proximal part of 2 muscles. The mAb against MyBP-C-slow labeled all fibers, but fibers containing MyHCI were generally more strongly stained. In the levator palpebrae, immunostaining with anti-MyBP-C-fast was present in some fibers labeled with anti-MyHCIIa and/or anti-MyHCeom. MyBP-C-fast and -intermediate were not detected biochemically in the EOMs. CONCLUSIONS: The lack of MyBP-C-fast and intermediate is an additional feature of the human EOM allotype. The true EOMs have a unique myofibrillar protein isoform composition reflecting their special structural and functional properties. The levator palpebrae muscle phenotype is intermediate between that of the EOMs and the limb muscles.

  • 150.
    Kjellgren, Daniel
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Andersen, Jesper
    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.
    Myosin heavy chain isoforms in human extraocular muscle2003In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 44, no 4, p. 1419-1425Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate the myosin heavy chain (MyHC) composition of human extraocular (EOM) and levator palpebrae (LP) muscle fibers. METHODS: Adult human EOMs and LP were studied with SDS-PAGE, immunoblots, and immunocytochemistry, with antibodies against six MyHC isoforms. Myofibrillar adenosine triphosphatase (mATPase) and reduced nicotinamide adenine dinucleotide (NADH)-TR activity and fiber area were also determined. RESULTS: Most of the fibers in both layers stained strongly with anti-MyHCIIa. Approximately 14% of the fibers in the global layer and 16% in the orbital layer were labeled with anti-MyHCI. The remaining 24% of the fibers in the global layer and 3% in the orbital layer were not stained with either of these two antibodies, but were reactive to anti-MyHCeom (MyHCeom(pos)/MyHCIIa(neg) fibers). The fibers stained with anti-MyHCI had acid-stable mATPase activity, and the remainder of the fibers had alkaline-stable mATPase activity. Almost all the slow fibers stained with both anti-MyHCI and anti-MyHCslow tonic in both layers. Anti-MyHCalpha-cardiac stained approximately 26% of these slow fibers in the orbital layer and 7% in the global layer. Some slow fibers in both layers lacked staining with anti-MyHCslow tonic or with anti-MyHCalpha-cardiac. MyHCemb and/or MyHCeom were also present in some of the fibers of all the groups. The LP did not stain with anti-MyHCslow tonic. CONCLUSIONS: The present study revealed that the human EOMs have a very complex fiber type and MyHC composition and differ significantly from the EOMs of other species. The features of the LP were distinct from those of the four recti, the obliquus superior, and the limb muscles.

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